A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright Ó2003 by ICON Group International, Inc. Copyright Ó2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Colon Cancer: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83616-7 1. Colon Cancer-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on colon cancer. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications.
Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON COLON CANCER ....................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Colon Cancer............................................................................... 55 E-Journals: PubMed Central ..................................................................................................... 175 The National Library of Medicine: PubMed .............................................................................. 180 CHAPTER 2. NUTRITION AND COLON CANCER ........................................................................... 305 Overview.................................................................................................................................... 305 Finding Nutrition Studies on Colon Cancer ............................................................................. 305 Federal Resources on Nutrition ................................................................................................. 314 Additional Web Resources ......................................................................................................... 314 CHAPTER 3. ALTERNATIVE MEDICINE AND COLON CANCER ..................................................... 319 Overview.................................................................................................................................... 319 National Center for Complementary and Alternative Medicine................................................ 319 Additional Web Resources ......................................................................................................... 332 General References ..................................................................................................................... 338 CHAPTER 4. DISSERTATIONS ON COLON CANCER ....................................................................... 339 Overview.................................................................................................................................... 339 Dissertations on Colon Cancer .................................................................................................. 339 Keeping Current ........................................................................................................................ 340 CHAPTER 5. CLINICAL TRIALS AND COLON CANCER.................................................................. 341 Overview.................................................................................................................................... 341 Recent Trials on Colon Cancer .................................................................................................. 341 Keeping Current on Clinical Trials ........................................................................................... 360 CHAPTER 6. PATENTS ON COLON CANCER .................................................................................. 363 Overview.................................................................................................................................... 363 Patents on Colon Cancer............................................................................................................ 363 Patent Applications on Colon Cancer........................................................................................ 388 Keeping Current ........................................................................................................................ 404 CHAPTER 7. BOOKS ON COLON CANCER ..................................................................................... 405 Overview.................................................................................................................................... 405 Book Summaries: Federal Agencies............................................................................................ 405 Book Summaries: Online Booksellers......................................................................................... 408 The National Library of Medicine Book Index ........................................................................... 409 Chapters on Colon Cancer ......................................................................................................... 410 CHAPTER 8. MULTIMEDIA ON COLON CANCER........................................................................... 415 Overview.................................................................................................................................... 415 Video Recordings ....................................................................................................................... 415 Bibliography: Multimedia on Colon Cancer .............................................................................. 416 CHAPTER 9. PERIODICALS AND NEWS ON COLON CANCER........................................................ 419 Overview.................................................................................................................................... 419 News Services and Press Releases.............................................................................................. 419 Newsletters on Colon Cancer..................................................................................................... 425 Newsletter Articles .................................................................................................................... 426 Academic Periodicals covering Colon Cancer ............................................................................ 426 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 429 Overview.................................................................................................................................... 429 U.S. Pharmacopeia..................................................................................................................... 429 Commercial Databases ............................................................................................................... 430 Researching Orphan Drugs ....................................................................................................... 430
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Contents APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 435 Overview.................................................................................................................................... 435 NIH Guidelines.......................................................................................................................... 435 NIH Databases........................................................................................................................... 437 Other Commercial Databases..................................................................................................... 442 The Genome Project and Colon Cancer ..................................................................................... 442 APPENDIX B. PATIENT RESOURCES ............................................................................................... 447 Overview.................................................................................................................................... 447 Patient Guideline Sources.......................................................................................................... 447 Associations and Colon Cancer.................................................................................................. 462 Finding Associations.................................................................................................................. 468 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 471 Overview.................................................................................................................................... 471 Preparation................................................................................................................................. 471 Finding a Local Medical Library................................................................................................ 471 Medical Libraries in the U.S. and Canada ................................................................................. 471
ONLINE GLOSSARIES ................................................................................................................ 477 Online Dictionary Directories ................................................................................................... 479 COLON CANCER DICTIONARY.............................................................................................. 481 INDEX .............................................................................................................................................. 565
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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with colon cancer is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about colon cancer, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to colon cancer, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on colon cancer. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to colon cancer, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on colon cancer. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON COLON CANCER Overview In this chapter, we will show you how to locate peer-reviewed references and studies on colon cancer.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and colon cancer, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “colon cancer” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: ·
Factors Influencing Intention to Obtain a Genetic Test for Colon Cancer Risk: A Population-based Study Source: Preventive Medicine. 34(6):567-577, June 2002. Summary: Researchers conducted a population-based study to examine factors that influence the intention to get a genetic test for colon cancer risk. They conducted a telephone survey of adult residents age 18 to 75 years in New Hampshire, Maine, and Vermont, from November 1997 to April 1998. The researchers contacted 2,675 households and completed 2,001 interviews. After exclusions, the final sample size was 1,836. The surveys assessed (1) intention to get a genetic test for colon cancer risk, (2) benefits of and barriers to genetic testing for cancer risk, (3) perceived susceptibility to colon cancer, (4) optimism, (5) awareness of genetic testing for cancer risk, (6) family history of cancer, (7) socioeconomic status (SES), (8) age, and (9) other demographic
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characteristics. Univariate analysis showed that (1) 43 percent of the respondents had heard of genetic testing for cancer in general, (2) only 25.9 percent had heard of genetic testing for colon cancer, (3) the respondents generally perceived themselves to be not susceptible to colon cancer, (4) few respondents reported a family history of colon cancer, (5) the respondents generally agreed that genetic testing for cancer risk would be a benefit, and (6) few respondents reported barriers to genetic testing. Multivariate analysis showed that (1) perceived susceptibility, perceived benefits, perceived barriers, optimism, and pessimism were directly related to the intention to undergo genetic testing for colon cancer risk; and (2) age, SES, and family history all had a significant indirect effect on likelihood for genetic testing. The researchers conclude that these results suggest effective educational strategies to improve the decision-making process to undergo genetic testing for colon cancer risk in the general population. 2 figures, 3 tables, 51 references. ·
Colon Cancer Screening in the Ambulatory Setting Source: Preventive Medicine. 35(3):209-218, September 2002. Summary: Researchers conducted a retrospective review of medical records from primary care practices at the University of California at San Francisco Medical Center to assess patient and clinician factors associated with colon cancer screening. They included 6,039 patients age 50 to 74 years who had at least one visit between July 1995 and June 1997. The primary outcomes were fecal occult blood testing (FOBT) in the previous 1 or 2 years or sigmoidoscopy in the previous 5 or 10 years. Secondary outcomes were colonoscopy in the previous 10 years or any other screening procedure. The mean age of the patients was 61 years. The median number of visits was 4.3 and more than two-thirds of the patients had been seen in the previous 6 months. About half of the patients had public insurance, 42 percent had private insurance, and 10 percent had either another type of insurance or no insurance. Results showed that (1) 41 percent of patients had received FOBT in the past year and 47 percent in the past 2 years, (2) about 25 percent had undergone sigmoidoscopy in the past 5 or 10 years, (3) only 3 percent had undergone colonoscopy, and (4) only 14 percent had received FOBT in the past year and sigmoidoscopy in the past 5 years. Predictors of FOBT screening were (1) patient age, (2) Asian ethnicity, (3) number of visits during the study period, (4) having a recent last visit, and (5) having private insurance. Predictors of sigmoidoscopy were similar, but also included family history of colon cancer and having managed care insurance. Patients of nurse practitioners were less likely to receive FOBT compared with patients of physicians and patients of residents were less likely to undergo sigmoidoscopy than were patients of faculty. The researchers conclude that colon cancer screening rates among this study population were low, especially among patients who were younger, had been seen less frequently, who were uninsured, or who did not have managed care insurance. 5 tables, 23 references.
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Colon Cancer: Prevention, Diagnosis, Treatment Source: Gastroenterology Nursing. 25(5):204-211, September-October 2002. Summary: Colorectal cancer (CRC) is the second leading cause of death from cancer in the United States. The authors review (1) the anatomy and physiology of the colon, (2) risk factors for developing CRC, (3) preventive and screening measures to reduce disease incidence, (4) diagnostic procedures to detect CRC and colon polyps, and (5) current therapies to treat the disease. Genetics and increasing age are risk factors that cannot be changed. Dietary modifications, such as a low-fat, high-fiber diet supplemented with antioxidants, vitamins A, C, and E, increased calcium and selenium,
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and daily aspirin and nonsteroidal anti-inflammatory agents, have all shown benefits in limited studies. Screening has proven to be an effective tool to prevent CRC in many studies. Current screening guidelines include (1) a yearly fecal occult blood test (FOBT), (2) flexible sigmoidoscopy every 5 years after age 50 years, (3) combination of FOBT and flexible sigmoidoscopy every 5 years, (4) double contrast barium enema (DCBE) and flexible sigmoidoscopy every 5 years, and (5) colonoscopy every 10 years. A cost analysis of screening colonoscopy yields a cost of $25,000 per year of life saved. The federal government considers $40,000 per year of life saved to be cost effective. With less than 40 percent of all eligible persons being screened for CRC currently, cost has become less of an issue than the general public's knowledge of the necessity for screening. The authors conclude that nurses need to educate the public about CRC and screening, since reliance on the media to educate the public is not sufficient. 4 tables, 26 references. ·
Virtual Colonoscopy Is a Promising Technology for Colon Cancer Screening Source: Primary Care and Cancer. 21(3):12-13, March 2001. Summary: According to Dr. Richard J. Farrell, virtual colonoscopy is an accurate screening method for colorectal cancer in lesions greater than 10 millimeters. This new screening method also has good patient tolerance. Virtual colonoscopy, or computed tomography (CT) colonoscopy, uses thin-section, helical CT to generate high-resolution two-dimensional axial images and three-dimensional endoluminal images. Physicians at the Beth Israel Deaconess Hospital in Boston recruited 100 patients at high risk for colorectal cancer and polyps. All underwent virtual colonoscopy prior to elective conventional colonoscopy. Using conventional colonoscopy, 45 of these patients had normal findings. In the other 55 patients, the researchers found 88 polyps and 13 masses, including 9 carcinomas. Virtual colonoscopy found (1) 12 (90 percent) of the 13 masses, all of which were greater than 20 millimeters; (2) 28 (92 percent) of 31 polyps that were greater than 10 millimeters; (3) 15 (65 percent) of 23 polyps that were 6 to 9 millimeters; and (4) 12 (35 percent) of 34 polyps that were 5 millimeters or smaller. There were 11 false-positive findings of polyps and 3 false-positive findings of masses, resulting in a specificity of 90 percent. Dr. Farrell indicated that conventional colonoscopy remains the gold standard, but virtual colonoscopy is a good diagnostic tool. 1 figure.
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Inflammatory Bowel Disease Flare, or Colon Cancer? Source: Primary Care and Cancer. 21(1):38-41, 58, January 2001. Summary: A physician discusses the risk of colorectal cancer in patients with chronic inflammatory bowel disease (IBD) and the need for a colonoscopic surveillance program throughout their lives. While the risk of colorectal cancer has long been known in ulcerative colitis patients, only recently has the colon cancer risk of Crohn's colitis been recognized as being of similar magnitude. It is unclear whether coincident colon cancer risk factors, such as a family history of colorectal neoplasm, further heighten the cancer risk in these patients. However, other contributing factors, such as the complication of primary sclerosing cholangitis, have been recognized. Colonoscopy is the screening tool of choice in IBD rather than sigmoidoscopy. Colon cancer in IBD typically follows a premalignant dysplastic phase. The likelihood of finding colon cancer at colectomy after high-grade dysplasia has been identified is about 40 percent. Symptoms of new colon cancer in individuals may be exceedingly difficult to distinguish from an exacerbation of colitis. Symptoms such as weight loss, loss of appetite, or progressive anemia should be evaluated aggressively to allow for prompt surgical resection in response to the development of dysplasia or cancer. It may be appropriate to offer prophylactic colectomy to younger ulcerative colitis patients once their colitis has been established for
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a decade or more, as opposed to undergoing colonoscopy every year or two for the remainder of their lives. 3 figures, 3 tables, 10 references. ·
Colon Cancer in Women Source: AWHONN Lifelines. 5(3):26-32, June 2001. Summary: The author provides women's health care nurses with information on basic genetic concepts, the role of genes in the development of cancer, and cancer syndromes and cancer genetic services regarding colon cancer. Colon cancer genes are dominant, meaning that a single copy can greatly increase an individual's cancer risk. All cancers are genetic in origin, but hereditary cancer results from (1) the presence of a genetic mutation in a germ cell that is reproduced in every cell of an individual's body, (2) the somatic mutation of the other gene in that pair, and (3) additional somatic mutations in the same cell line until control of cell growth and differentiation is lost. The two most common hereditary colon cancer syndromes are hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP). HNPCC is characterized by (1) the presence of syndrome cancers in many individuals within a family, (2) more than one primary cancer in an individual, (3) high incidence of colon cancers, (4) early age at onset, and (5) proximal location of most of the cancers. The risk for colon cancer in an HNPCC mutation carrier is 85 to 90 percent for males and as low as 54 percent for females. FAP is characterized by (1) the presence of hundreds to thousands of polyps in the colon, (2) average age at polyp onset of 15 years, and (3) 100 percent risk of colon cancer if left untreated by the fourth decade. The author provides information on managing HNPCC and FAP. When a hereditary colon cancer syndrome is diagnosed families can benefit from genetic counseling and genetic testing. The author concludes that women's health nurses are in an ideal position to promote and support the cancer screening recommendations and to help with overcoming barriers to screening among female mutation carriers. 2 figures, 2 tables, 15 references.
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Patient Experience and Preferences Toward Colon Cancer Screening: A Comparison of Virtual Colonoscopy and Conventional Colonoscopy Source: Gastrointestinal Endoscopy. 54(3):210-315, 2001. Summary: Researchers assessed patient tolerance of virtual colonoscopy (VC) compared to conventional colonoscopy (CC), characterizing patient preferences for these techniques. People referred to a Veterans Affairs Medical Center gastrointestinal clinic for colonoscopy for any indication were recruited to undergo VC prior to receiving CC. CC was performed with the patient under conscious sedation, while VC was performed without sedation. They completed a questionnaire after the VC and again after completing both tests. The questionnaire assessed overall pain, discomfort, and lack of respect. Their preferences for VC versus CC were determined using a time tradeoff technique. To verify the stability of responses, participants completed an additional questionnaire by mail at 24 hours. At both 0 and 24 hours, participants reported more pain and discomfort and less respect after VC than after CC. They preferred CC and said they would be willing to wait longer for CC as opposed to undergoing VC. Both procedures were well-tolerated overall. The researchers conclude that improvements in patient tolerance and acceptance of VC are necessary if this test is to become competitive as an alternative screening modality. 6 figures, 3 tables, 12 references.
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Colon Cancer Screening With Virtual Colonoscopy: Promise, Polyps, Politics Source: American Journal of Roentgenology. 177(5):975-988, November 2001.
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Summary: The author discusses virtual colonoscopy as a potential primary means of screening for colon cancer, which could return radiologists to a major role in the prevention of colon cancer. Research suggests that its accuracy is comparable to conventional colonoscopy in detecting polyps of significant size (greater than 10 mm), with few false positives. Virtual colonoscopy has heightened awareness of the natural history of colonic polyps, especially in terms of identifying an appropriate target size for detection in colorectal screening programs. Polyps under 10 mm are often either hyperplastic on histology or unlikely to progress to frank cancer in the patient's lifetime, so they are of little clinical significance for the average adult. The rationale for detecting and removing every colonic polyp regardless of size has come under increasing scrutiny in the context of cost-benefit analysis of various test strategies for colorectal cancer screening. Virtual colonoscopy may allow patients to receive reliable information about the status of their colonic mucosa noninvasively, therefore making more informed decisions about whether to proceed to conventional colonoscopy for polypectomy. Cancer researchers are working to improve the speed of image analysis, use of computer-assisted methods for polyp detection, magnetic resonance colonography, and oral contrast tagging of fecal contents in order to avoid the need for rigorous bowel preparation, thus improving patient compliance. 10 figures, 3 tables, 87 references. ·
Which Colon Cancer Screening Test Should I Get? Source: Harvard Women's Health Watch. 9(2):8, October 2001. Summary: This article discusses options for colon cancer screening. There is no single test officially recommended for colorectal cancer, although experts agree that people should begin screening by age 50 years. The three commonly used screening tests are (1) fecal occult blood test (FOBT), (2) sigmoidoscopy, and (3) colonoscopy. If the FOBT detects blood or the sigmoidoscopy shows something abnormal, doctors refer their patients for a followup colonoscopy. Most physicians advise screening beginning at age 50 years by one of two methods for people at average risk: (1) Sigmoidoscopy every 5 years and an annual FOBT or (2) colonoscopy every 10 years without FOBT or sigmoidoscopy. Virtual colonoscopy is a new technology that examines the colon via computed tomography and virtual reality software.
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Which Colon Cancer Screening Test? A Comparison of Costs, Effectiveness, and Compliance Source: American Journal of Medicine. 111(8):593-601, December 1, 2001. Summary: Researchers performed a cost-effectiveness analysis of colonoscopy (COL) versus other colorectal cancer (CRC) screening tests. The impetus for the study was recent media reports that have advocated the use of COL for CRC screening, tempered by the realization that COL is expensive compared with other screening tests, such as flexible sigmoidoscopy (SIG) and the fecal occult blood test (FOBT). Investigators constructed a Markov cost-effectiveness model to examine screening for CRC. The model tested variations in the timing and frequency of the screening tests and estimated the effects of compliance, costs, test characteristics, and the natural history of CRC. Once a lifetime and twice a lifetime COL were selected as strategies that might optimize compliance. Researchers compared costs and effectiveness of COL with those of FOBT, SIG, and SIG combined with FOBT. Sensitivity analyses were also performed to evaluate factors that have the greatest impact on the cost-effectiveness of CRC screening. All strategies (COL, FOBT, and SIG) are cost-effective when compared against no screening, at less than $20,000 per life-year saved (LYS). Assuming 100 percent compliance, SIG combined with FOBT is slightly more cost-effective than twice a lifetime COL for
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patients age 50 and 60 years, but is substantially more expensive with an incremental cost-effectiveness of $390,000 per additional LYS. Compliance with the primary screening tests (FOBT and SIG) and COL followup for polyps, however, would affect screening decisions. As compliance decreases, SIG and FOBT become less cost-effective and more costly. At 75 percent compliance, the incremental cost-effectiveness of combined SIG plus FOBT compared with twice in a lifetime COL increases to over $330,000 per LYS. With further decreases in the rates of patient compliance, COL becomes more cost-effective than combined SIG plus FOBT. COL at ages 50 and 60 years becomes the preferred test regardless of the level of compliance with SIG or FOBT used as the primary screening test. Sensitivity analyses show that the costs of COL and the proportion of cancer arising from polyps also affect cost-effectiveness. At more likely levels of compliance (50 percent or less) or if more than 50 percent of cancers arise from polyps, COL becomes the screening strategy of choice unless its costs are very high. Researchers conclude that COL appears preferable to current CRC screening recommendations because it becomes and maintains its cost-effectiveness at lowcompliance levels. CRC screening recommendations should be tailored to compliance levels achievable in different practice settings. 2 figures, 3 tables, 72 references. ·
Colon Cancer Screening (USPSTF Recommendation) Source: Journal of the American Geriatrics Society. 48(3):333-335, March 2000. Summary: The United States Preventive Services Task Force (USPSTF) provides recommendations to help practitioners when advising their older patients in the decision to undergo colon cancer screening. Current methods for early detection of colorectal cancer include (1) digital rectal examination (DRE), (2) sigmoidoscopy, (3) fecal occult blood testing (FOBT), or (4) a combination of sigmoidoscopy and FOBT. Colonoscopy and double-contrast barium enema are alternatives and can be used for evaluating abnormal findings. Screening outcomes are reduced morbidity and mortality as a result of early detection of colon cancer, or prevention of colon cancer through detection and removal of adenomatous polyps. Colorectal cancer is the second leading cancer and cancer-related death, and its incidence continues to rise with increasing age. Colorectal cancer screening is recommended for all persons age 50 and older. There is limited information on the optimal ages to start and stop screening. Good evidence supports annual FOBT. There is not enough information to support a screening interval for sigmoidoscopy, but other groups have recommended every 3 to 5 years. There is not enough information to recommend for or against routine screening with DRE, barium enema, or colonoscopy. For high-risk persons, regular endoscopic screening is appropriate. The best approach to a complete colorectal evaluation is to have a complete colonoscopy. In a followup commentary, the editors note that (1) for screening to be effective in reducing morbidity and mortality, it needs to be followed up with diagnostic colonoscopy when screening is positive and by surgery when cancer is detected; and (2) the strongest current evidence supports annual FOBT and flexible sigmoidoscopy every 5 years. 22 references.
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Novel Approaches to the Prevention of Colon Cancer by Nutritional Manipulation and Chemoprevention Source: Cancer Epidemiology Biomarkers and Prevention. 9(3):239-247, March 2000. Summary: The author details the preventive strategies to reduce the incidence and mortality of large bowel cancer by nutritional manipulation and chemopreventive agents. There is ample epidemiological and experimental evidence that dietary factors account for about 50 percent of the risk for developing colon cancer. Most research has
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focused on the role of dietary fat and fiber in the development of colon cancer. Research has shown that (1) colon cancer is associated with total dietary fat, (2) dietary fat influences the composition of intestinal microflora that is likely to be involved in the development of colon cancer, (3) the link between saturated fat intake and colon cancer is strong, (4) diets rich in polyunsaturated fats with omega-3 fatty acids may reduce the risk of colon cancer, and (5) high-fiber diets may reduce the risk of colon cancer. Chemoprevention is the administration of naturally-occurring or synthetic chemical agents that may prevent cancer development. The development of chemopreventive strategies for reducing colon cancer risk has been facilitated by the use of animal models, which mimic the neoplastic process that occurs in humans. Three broad categories of chemopreventive agents are those that can (1) prevent the formation of carcinogenic compounds from their precursors, (2) block the metabolic activation of carcinogens, and (3) suppress the expression of neoplasia in cells exposed previously to an effective dose of carcinogen. Possible chemopreventive agents include (1) phytochemicals, (2) nonsteroidal antiinflammatory drugs, and (3) organoselenium. The author concludes that (1) data support the concept that dietary factors are key modulators of colon cancer, and (2) chemoprevention has the potential to be a major component of colon cancer control. 6 figures, 76 references. ·
Colon Cancer Screening Among Older Women Caregivers Source: Cancer Nursing. 23(2):109-116, April 2000. Summary: Researchers studied the colorectal cancer screening of older women in California who are the primary caregivers for an ill spouse or parent. The researchers used an exploratory descriptive correlation design to study the frequency of screening, and to find the relationship of caregiving and perceptions of health to participation in screening. A total of 52 women agreed to participate. Of these women, (1) 55 percent were age 65 and older, (2) 64 percent were married, (3) 40 percent were working fulltime, (4) 90 percent lived with the patient, (5) 65 percent provided at least 8 hours of care a day, and (6) 44 percent provided almost continuous care. The researchers assessed colorectal cancer screening through selected questions from the Behavioral Risk Factor Survey of 1991 regarding sigmoidoscopy and fecal occult blood testing (FOBT), and perceptions of getting and surviving colorectal cancer. The researchers assessed feelings about the burden of caregiving with the Caregivers' Appraisal scale. Results showed that (1) 64 percent of participants never underwent combined sigmoidoscopy and FOBT; (2) 47 percent had never been tested with sigmoidoscopy, and of those who had been tested, only 22 percent met the recommended screening interval guideline; (3) 80 percent had undergone FOBT, but only 28 percent met the recommended screening interval guideline; and (4) only 20 percent had comprehensive cancer screening. Other results showed that (1) married women were significantly more likely to have participated in sigmoidoscopy screening, (2) the mean age for participants in sigmoidoscopy screening was significantly higher than for nonparticipants, (3) participation in sigmoidoscopy and FOBT were not significantly associated with years of caregiving or hours involved daily in caregiving, (4) caregiver burden was not significantly associated with participation in screening, and (5) participants in sigmoidoscopy had significantly better health perceptions. The researchers concluded that (1) older women's participation in colon cancer screening was lower than recommended, (2) caregiving burden and advancing age were not major barriers to participation in screening, and (3) women with poorer health and less satisfaction with caregiving had lower levels of participation. 4 tables, 27 references.
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Videotape-based Decision Aid for Colon Cancer Screening: A Randomized, Controlled Trial Source: Annals of Internal Medicine. 133(10):761-769, November 2000. Summary: Researchers conducted a randomized, controlled trial among three community private care practices in central North Carolina to test whether a decision aid consisting of an educational video, targeted brochure, and chart marker increased performance of colon cancer screening in primary care practices. Of 1,657 consecutive adult patients age 50 to 75 who were contacted, 651 (39 percent) agreed to participate; of these, 249 were eligible. Eligible patients had no personal or family history of colon cancer and had not had fecal occult blood testing in the past year or flexible sigmoidoscopy, colonoscopy, or barium enema in the past 5 years. Researchers randomly assigned participants to view an 11-minute video about colon cancer screening (intervention group) or a video about automobile safety (control group). After viewing the video, intervention group participants chose a color-coded educational brochure (based on stages of change) to indicate their degree of interest in screening. A chart marker of the same color was attached to their charts. Controls received a generic brochure on automobile safety with no chart marker attached. Frequency of screening test ordering as reported by participants and frequency of completion of screening tests as verified by chart review served as measurements of the outcome of the campaign. Fecal occult blood testing or flexible sigmoidoscopy was ordered for 47.2 percent of the intervention participants and 26.4 percent of the controls. Screening tests were completed by 36.8 percent of the intervention group and 22.6 percent of the control group. The authors conclude that a decision aid consisting of an educational video, brochure, and chart marker increased ordering and performance of colon cancer screening tests. 1 figure, 3 tables, 25 references.
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Colon Cancer Screening Source: Gastroenterology. 119(3):837-853, September 2000. Summary: The author reviews issues associated with colorectal cancer (CRC) screening. The review focuses on how CRC screening is currently applied as a result of advances made in three areas: (1) Controlled studies convincingly showing that CRC mortality is reduced with fecal occult blood testing and sigmoidoscopy screening, (2) family history of colon cancer confirming an increased risk of CRC in relatives, and (3) an understanding of colon cancer genetics leading to genetic testing for the diagnosis of inherited syndromes of CRC. Issues associated with screening persons at average risk for CRC that are discussed include (1) evidence for CRC screening effectiveness, (2) costeffectiveness, (3) public adherence to screening guidelines, and (4) third-party reimbursement. Issues associated with screening persons with inherited risk factors for CRC include (1) familial adematous polyposis, (2) hereditary nonpolyposis CRC, (3) hamartomatous polyposis conditions, and (4) costs associated with genetic testing methodology. The author concludes that the past decade has seen extraordinary advances in CRC screening. Average-risk screening has now been validated, and national public and professional educational efforts to increase awareness and participation in screening are under way. Family history has been recognized as a common risk factor for colon cancer and screening strategies that incorporate family history have been developed. The genes underlying the inherited syndromes of colon cancer have been identified and clinical genetic testing for these syndromes has become available. The future will probably include, among other things, the development of improved screening tests, validation of high-risk screening approaches, and the
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development of genetic testing for the less severe but more common forms of familial risk factors. 1 figure, 12 tables, 121 references. ·
American Gastroenterological Association Medical Position Statement: Impact of Dietary Fiber on Colon Cancer Occurrence Source: Gastroenterology. 118(6):1233-1234, June 2000. Summary: The official recommendations of the American Gastroenterological Association on the impact of dietary fiber on the occurrence of colon cancer were approved in 1999. Eating dietary fiber, fruits, vegetables, antioxidant vitamins, calcium, and folate negatively relates to the risk of developing colorectal cancer (CRC). Dietary fiber is the endogenous components of plant materials in the diet that resist digestion by enzymes produced by humans. It consists of nonstarch polysaccharides and nonpolysaccharides. Current research does not unequivocally support the protective role of fiber against developing CRC. However, critical analysis of the whole body of evidence from current studies supports an inverse association between dietary fiber and CRC risk. Although it is hard to make recommendations to patients without sufficient scientific evidence, most studies demonstrate the protective effects of total fiber intake 3 to 3.5 times higher than the mean dietary fiber intake of the United States adult population. Thus, it is reasonable to recommend total fiber intake of at least 30 to 35 grams per day. This fiber should come from all sources, including five to seven servings of fruits and vegetables per day and generous servings of whole grain cereals. Research indicates that the delay between exposure of migrants to urban-industrial diets and emergence of CRC may be 10 to 20 years. Therefore, appropriate diets may have their full impact in preventing CRC only decades after they are widely adopted. These delays must be considered when setting realistic targets for CRC prevention with dietary fiber. Because CRC is significantly age related, and its incidence rates increase with age from around age 60 years, fiber intervention should start 10 to 20 years before the peak age for CRC incidence. People at high risk of developing CRC are the ones who will most likely benefit from fiber intervention. Some research has identified a marked racial effect, with blacks having lower dietary fiber intakes than whites in both sexes and across age groups. Therefore, modifications in this group may be beneficial. Recommendations for prevention of CRC must include not only a diet high in fiber but also modifications to other lifestyle factors associated with an increased risk of CRC. 1 reference.
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AGA Technical Review: Impact of Dietary Fiber on Colon Cancer Occurrence Source: Gastroenterology. 118(6):1235-1257, June 2000. Summary: The author analyzed currently available data from clinical and epidemiological studies in humans on the effect of dietary fiber on colorectal carcinogenesis (CRC). This analysis included all human studies concerning CRC and its precursor, adenoma, and fiber, grains, cereals, vegetables, or fruits published in the English language from 1970 to 1999. The studies were located in the CANCERLIT and MEDLINE databases, in several extensive reviews, and in references in identified studies. This analysis focuses on (1) definition, sources, and consumption of dietary fiber; (2) epidemiological evidence (correlation studies, case-control studies, and prospective studies); (3) human intervention studies; (4) resistant starch and short-chain fatty acids; and (5) biological plausibility (potential mechanisms of action). The analysis concludes by presenting information on causal inference, magnitude of CRC risk reduction, dose of dietary fiber associated with decreased CRC risk, duration of intervention associated with decreased CRC risk, types of fiber or specific related
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components associated with decreased CRC risk, and target groups for fiber intervention. 6 tables, 131 references. ·
Colon Cancer Source: Journal of the American Medical Association (JAMA). 284(23):3086, December 20, 2000. Summary: This patient education page provides information on colon cancer, including risk factors, screening, lowering the risk, and information sources. Colon cancer or colorectal cancer is one of the most common types of cancer and is a major cause of cancer deaths. Colorectal cancer screening is important, especially among patients with high risk for colorectal cancer. Early detection can save lives by detecting the disease before it spreads. Risk factors include (1) age 50 years or older, (2) some types of colon polyps, (3) some other types of cancers, (4) a family history of colorectal cancer, (5) inflammatory bowel disease, (6) a diet low in fiber and high in fat, (7) a diet mostly from animal sources, (8) physical inactivity, and (9) obesity. Screening methods for colon cancer include (1) fecal occult blood testing, (2) sigmoidoscopy, and (3) colonoscopy. Ways to lower your risk of colon cancer include (1) telling your doctor if you have a family history of colorectal cancer, (2) early detection through screening, (3) eating a diet high in fiber and low in fat, (4) maintaining your ideal weight, (5) limiting the amount of animal fat in your diet, and (6) becoming physically active.
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Proportion of Colon Cancer Risk That Might Be Preventable in a Cohort of Middleaged U.S. Men Source: Cancer Causes and Control. 11(7):579-588, August 2000. Summary: Researchers performed an analysis of the proportion of colon cancer risk that might be preventable in a cohort of middle-age United States males using data from the Health Professionals Followup Study (HPFS) for the period 1986 to 1996. The HPFS is a cohort of 51,529 male dentists, osteopaths, optometrists, pharmacists, and veterinarians who were age 40 to 75 years at enrollment in 1986 and who completed a questionnaire including demographic information, medical history, and diet. Researchers examined six modifiable colon cancer risk factors from the HPFS and reported in the published literature: (1) Obesity, (2) physical inactivity, (3) alcohol consumption, (4) early adulthood cumulative cigarette smoking, (5) greater red meat consumption, and (6) no or low intake supplemental folic acid. Risk scores, defined as the sum of the six risk factors, ranged from 1 (better exposure) to 5 (worse exposure). To estimate the contribution of modifiable risk factors to colon cancer risk, researchers calculated the population attributable risk (PAR) percent, defined as the proportion of colon cancer risk in the cohort that might be attributable to the six factors and therefore might be avoidable. The final analysis included 47,927 men among whom 411 were diagnosed with colon cancer. After adjusting for age and family history of colorectal cancer and comparing the risk scores for the six modifiable colon cancer risks at or above the approximate 20th, 10th, or 5th percentiles versus below, the PAR percent increased from 39 to 48 to 55 percent, respectively. The risk scores were linearly related to the risk of colon cancer. For a one point increase in the risk score, the risk increased 8 percent for the total colon (10 percent for the distal colon, and 3 percent for the proximal colon). In the entire cohort, 39 percent of the colon cancer risk might be preventable if the risk score for the entire cohort fell in approximately the bottom 20 percent of the distribution. Comparing men with at least one risk factor to men without any risk factors, the PAR percent was 71 percent. Researchers conclude that the results of this analysis suggest that if all members of the HPFS cohort had a modifiable exposure
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distribution comparable to those with low risk scores, a large proportion of colon cancer risk might be avoidable. 3 tables, 41 references. ·
Colon Cancer Discovery and the American Cancer Society Neglect of Single Contrast Barium Enema Source: Journal of the Medical Association of Georgia. 89(1):50-53, Early Spring 2000. Summary: The author discusses the usefulness of the single contrast barium enema (SCBE) as a tool for colorectal cancer (CRC) screening. The article (1) summarizes the historical development of fluoroscopic screening for cancer; (2) discusses general considerations for cancer screening; and (3) discusses the efficacy of various screening modalities for CRC screening, including the fecal occult blood test (FOBT), rigid and flexible sigmoidoscopy (SIG), colonoscopy (COL), double-contrast barium enema (DCBE), and SCBE. The American Cancer Society (ACS) has not included SCBE in its recommendations for CRC screening, despite the fact that with modern X-ray equipment, SCBE can readily identify small lesions (benign and malignant) in the colon. The CRC screening tests recommended by the ACS (FOBT, SIG, COL, and DCBE) in the author's view, are inadequate. The FOBT, for example, has a very high false-negative rate even in patients with known asymptomatic carcinoma of the colon. SIG is limited by the fact that it can detect lesions only in the distal colon. COL and DBCE can examine the entire colon. Either is properly used as the initial study, that is, as an upper-tier procedure for persons at high risk for CRC. Neither COL nor DCBE are a screen. Their use in people at average risk for CRC is comprehensible only if another CRC screening method did not exist. DCBE and COL are very expensive, inconvenient, and cause discomfort. The problems with COL and DCBE make them unsuitable as a first-tier screening tool for persons at average risk for CRC. SCBE cancer detection, in the author's opinion, has the advantages of (1) simplicity, (2) safety, (3) clinic and office availability, (4) financial worth, (5) equipment availability, (6) familiarity, (7) low falsepositive rate, (8) low false-negative rate, and (9) least discomfort. More good will comes from finding existing cancers than overlooking a few small nonmalignant polyps; that is, preventing possible future cancer should not take precedence over finding cancer. The author concludes that SCBE is the CRC screen of choice. 2 figures, 23 references.
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Patterns of Colon Cancer Screening Among Companies in the U.S.: A Descriptive Survey Source: American Journal of Health Promotion. 13(3):146-148, January and February 1999. Summary: Researchers conducted a one-time descriptive survey of companies classified as Fortune 500 in 1994 or 1995 regarding the colon cancer education and screening services provided to company employees and their families. Of the 789 companies on the list, 479 responded to the survey (61 percent). More than 37 percent offered colon cancer education and awareness programs at the worksite. Only 24.2 percent provided some form of colon cancer screening at the worksite. Sixty-nine percent provided insurance coverage for some form of colon cancer screening offsite. Of the respondents, 72.9 percent provided screening for colon cancer either at the worksite, offsite through insurance, or both. Fifty-six percent of all respondents extended screening benefits to spouses, and 41.1 percent extended screening benefits to retirees. Seventeen percent of all companies surveyed had at least 51 percent of the workforce over age 40. Of these 82 companies, 68.3 percent provided screening for colon cancer either at the worksite, offsite through insurance, or both. The insurance industry, utility industry, gas and electric industry, and banking industry represented the largest percentages of the 349
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screening companies. Researchers concluded that employers need to be encouraged to play a larger role in the health of their workforce. 1 table, 10 references. ·
Meat Consumption, Genetic Susceptibility, and Colon Cancer Risk: A United States Multicenter Case-control Study Source: Cancer Epidemiology, Biomarkers and Prevention. 8(1):15-24, January 1999. Summary: Researchers examined meat consumption and molecular variants in the Nacetyltransferase 2 (NAT2) and glutathione-S-transferase M1 (GSTM1) genes as risk factors for colon cancer. The study was part of the Diet, Activity, and Reproductive Study of Colon Cancer, a multicenter case-control study conducted among persons living in northern California, Utah, and the metropolitan Twin Cities area in Minnesota. The cases consisted of 1,542 persons living in these areas who had been diagnosed with colon cancer between October 1, 1991, and September 30, 1994. The controls consisted of 1,860 persons, frequency matched to the cases according to sex and 5-year age group. Researchers computed the mutagen index (MI) as an estimate for exposure to mutagenic or carcinogenic substances. Associations between consumption of meat and type of meat preparation, and variations in NAT2 and GSTM1 gene status and colon cancer risk were evaluated by standard case control techniques. The amount of red and white meat consumed was not associated with an overall increase in colon cancer risk. Processed meat consumption was positively, but weakly, associated with an increase in colon cancer in men when the highest quintile of intake was compared against the lowest quintile, yielding an odds ratio (OR) of 1.4. The frequency of consumption of fried, broiled, baked, or barbecued meat, use of drippings, and doneness of meat was not significantly associated with increased colon cancer risk. The MI was slightly, positively associated with an increased colon cancer risk in men, the OR being 1.3. For women, no marked associations of red or white meat consumption with colon cancer risk were seen. No significant associations with increased colon cancer risk were observed for any of the NAT2 and GSTM1 gene variants. The observed associations with processed meat consumption were strongest for those with the intermediate or rapid NAT2 acetylator genotype. These associations were not significantly affected by GSTM1 gene status. Researchers concluded that this study provides little evidence for an association between meat consumption and colon cancer risk. It does provide some, although not strong, evidence for a modifying effect of molecular variants of the NAT2 gene on colon cancer risk. 7 tables, 69 references.
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Patient Preferences for Colon Cancer Screening Source: Journal of General Internal Medicine. 14(7):432-437, July 1999. Summary: Researchers conducted a study examining patient preferences for colorectal cancer (CRC) screening. They recruited 146 patients, age 50 to 75, 58 percent of whom were females, at a university internal medicine clinic between October and December 1997 for the study. None of the patients had a previous history of CRC. The participants were asked about their preferences for (1) annual screening with the fecal occult blood test (FOBT); (2) flexible sigmoidoscopy (FSIG) every 5 years; (3) both annual FOBT and FSIG every 5 years; or (4) no screening. They were asked their preferences at three points: (1) After receiving information about CRC and various screening options (testing procedure information); (2) after receiving information about the effectiveness of the various tests with no out-of-pocket cost information (test performance information); and (3) after receiving hypothetical out-of-pocket cost information ($10 per year for FOBT, and $150 per year for FSIG every 5 years; cost information). Nearly all patients self identified as either white (52 percent) or African American (43 percent). The overall level
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of education was low; 53 percent had not completed high school. Most (86 percent) had some type of health insurance. Slightly more than half (53 percent) reported ever having a test for CRC. Fourteen percent were unsure, and 33 percent believed they had never had such a test. When asked about specific tests, 59 percent of the participants reported ever having an FOBT, 22 percent reported ever having FSIG, and 13 percent reported ever having colonoscopy. Only 28 percent reported ever having had a previous conversation (defined as any discussion beyond simply ordering a test) with their provider about CRC screening. After receiving testing procedure information, the most popular test was FOBT alone, (45 percent) or combined with FSIG (38 percent). Few (13 percent) preferred FSIG alone. After receiving test performance information, more participants preferred both tests (47 percent), and fewer preferred FOBT alone (36 percent). After receiving cost information, the percentage preferring FOBT screening alone increased to 53 percent, while those preferring both FOBT and FSIG decreased to 31 percent. Fewer than 5 percent preferred no screening. An evaluation of factors predicting preference for CRC screening preference indicated that recalling a previous discussion of CRC screening was modestly associated with a patient's preference to have both FOBT and FSIG, as opposed to having either test alone. Having undergone any CRC screening test in the past was also associated with a preference for both tests. Having previously undergone FSIG was strongly associated with having both tests. Men were somewhat more likely to prefer both tests than women. Education, age, race, and insurance status were not significantly related to screening test preference. Researchers concluded that patient preferences for CRC screening are modestly sensitive to information about test performance, and strongly sensitive to out-of-pocket costs. The heterogeneity of patients' preferences for how to be screened supports the use of informed shared decision making as a possible means of improving CRC screening. 3 tables, 13 references. ·
Harvard Report on Cancer Prevention: Volume 3: Prevention of Colon Cancer in the United States Source: Cancer Causes and Control. 10:167-180, 1999. Summary: The authors discuss preventing colon cancer in the United States. Topics include (1) the burden of colon cancer, (2) the natural history of colon cancer, (3) primary prevention of colon cancer, (4) screening for colon cancer, and (5) strategies for preventing colon cancer. The lifetime risk of colon cancer for the average American is approximately 6 percent, or 1 in 18. The incidence of colon cancer increases sharply after age 35, with 90 percent of disease occurring in persons over age 50. At all ages, colon cancer incidence is slightly higher among men than women. Incidence rates have recently begun to decrease after increasing for several decades. Between 1973 and 1985, the age-standardized incidence of colon cancer rose from 32 to 38 cases per 100,000. Since 1985, however, the incidence rate has decreased by about 20 percent, to 31 cases per 100,000 individuals in 1995. These trends are thought to reflect the earlier detection and increased removal of premalignant polyps. Primary prevention of colon cancer focuses on personal risk factors for colon cancer, since 75 percent of all colon cases occur in people who do not have predisposing factors, such as family history and inflammatory bowel disease. Risk factors include (1) physical inactivity; (2) high intake of red meat; (3) obesity; (4) not consuming enough vegetables, fruit, and fiber; and (5) alcohol and tobacco use. Regular aspirin use may reduce risk, and use of postmenopausal hormones may reduce women's risk of colon cancer. Colon screening techniques used include (1) the fecal occult blood test (FOBT); and (2) flexible sigmoidoscopy (FSIG). Both the FOBT and FSIG have been demonstrated to be effective in reducing colon cancer mortality; however, neither procedure is well utilized in the
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United States. If screening by either FOBT or FSIG were implemented on a population wide level, colon cancer incidence and mortality could be substantially reduced. Strategies for preventing colon cancer should focus on cultivating an environment that promotes policy initiatives, social measures, and individual behaviors supportive of health. These can focus on delivering messages such as (1) increasing physical activity, (2) reducing consumption of red meat, (3) taking a daily multivitamin containing 0.4 milligram of folic acid, (4) maintaining a healthy weight, (5) increasing vegetable consumption, (6) limiting alcohol intake, (7) avoiding smoking, and (8) being screened regularly. These strategies can be implemented in health care provider, regulatory, and community settings. 3 figures, 4 tables, 103 references. ·
Perceived Benefits of and Barriers to Participation in a Phase I/II Colon Cancer Chemoprevention Trial Source: Journal of Cancer Education. 14(2):83-87, Summer 1999. Summary: Researchers investigated peoples' perceptions about the benefits of participating in a phase I/II colon cancer chemoprevention trial, noting barriers to participation, likelihood of participating in future trials, willingness to pay for trialrelated expenses, and interest in posttrial continuation of the drug. Participants were healthy people at risk for colorectal carcinoma at a university comprehensive cancer center. The study used a double-blind, placebo-controlled design, with objectives concerning toxicity and impact of liquid difluoromethylornithine (DFMO), 0.5 g/m2, taken daily by mouth, on colorectal mucosal biomarkers. At baseline, participants underwent blood sampling, audiography, flexible sigmoidoscopy, and colonoscopy. Multiple biopsies of the colonic mucosa were taken with each endoscopic procedure. At 3 months, researchers performed blood sampling and flexible sigmoidoscopy. At 6 and 9 months, blood sampling was done. At 1 year, the drug was stopped, and researchers repeated all baseline measures. Participants completed mailed questionnaires measuring their perceptions no more than 3 months after completion of the trial. Questionnaires examined demographics, participation in other research studies, perceptions of the benefits of and barriers to participation, likelihood of future participation in clinical trials, willingness to pay out-of-pocket expenses, and interest in posttrial continuation of the DFMO regimen. Results indicated that the most highly-rated benefits of participation were the possibility of reducing the chance of getting cancer and the possibility of preventing others from getting cancer in the future. Barriers included billing problems and having colonoscopies done. Only 29 percent would have joined the trial if they had had to pay for trial-related costs. Most respondents indicated that they would definitely or probably continue taking DFMO in the future if it was proven effective. 3 figures, 1 table, 11 references.
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Workplace Programs May Reduce Colon Cancer Mortality Source: Primary Care and Cancer. 19(9)11-13, April 1999. Summary: Colon cancer education programs at Fortune 500 companies could play a significant role in reducing deaths from the disease. The first study to assess corporate commitment to colon cancer education involved a survey of 479 Fortune 500 companies. It found that 73 percent of the Fortune 500 companies surveyed provided insurance coverage for colon cancer screening, but fewer than 40 percent offered colon cancer education and awareness programs, and even fewer offered worksite screenings. The study's author suggested that employers offer education and awareness programs for colon cancer to their employees. More than 90 percent of colon cancer can be cured if the disease is detected early, but most people are not tested early or often enough. Only 37
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percent of all colorectal cancers are diagnosed in the early, localized stage. Although it is recommended that individuals over age 40 receive regular screening for colon cancer, compliance with these guidelines in medical practice is less than 50 percent. One study found that while 88 percent of primary care physicians surveyed agreed completely or partly with current American Cancer Society recommendations for colon cancer screening, only 34 percent regularly referred or scheduled patients for screening. By simply encouraging employees to seek routine colon cancer screening, employersponsored education programs can have a significant public health impact. Of the 349 companies providing worksite screening and/or insurance, the insurance industries, utilities, and banking industry represented the largest percentages. ·
Comparison of Breast and Colon Cancer Incidence Rates Among Native Asian Indians, U.S. Immigrant Asian Indians, and Whites Source: Journal of the American Dietetic Association. 99(10):1275-1277, October 1999. Summary: Researchers performed a comparison analysis of breast and colon cancer incidence among Native Asian Indians (NAI's), United States immigrant Asian Indians (IAI's), and whites. Breast and colon cancer incidence rates for IAI's were estimated using data from the National Cancer Institute's Surveillance, Epidemiological, and End Results program for 1988 to 1991 and the Census Bureau. Rates for India were estimated from data reported for four metropolitan areas (Ahmedabad, Bangalore, Madras, and Bombay) for the years 1983 to 1987. The age-adjusted incidence rates for breast cancer among NAI, IAI, and United States white women were 28.4, 93.1, and 153.2 cases per 100,000 women, respectively. These produced breast cancer relative risks (RR's) of 3.30 for IAI's compared with NAI's and 0.61 for IAI's compared with United States white women. The incidence rates of colon cancer among NAI, IAI, and United States white men were 2.9, 26.6, and 43.2 cases per 100,000 population, respectively. These yielded RR's of (1) 9.2 for IAI men compared with NAI men, and (2) 0.62 for NAI men compared with United States white men. The colon cancer incidence rates among NAI, IAI, and United States white women were 2.8, 6.8, and 43.8 cases per 100,000, respectively. This yielded RR's of (1) 2.4 for IAI women compared with NAI women, and (2) 0.16 for NAI women compared with United States white women. Researchers concluded that immigration of Indians into the United States seems to be associated with an increased risk of breast cancer and colon cancer. These findinggs support the hypothesis that certain dietary or endocrine factors, although they increase the risk of cardiovascular disease among NAI's, may be protective against cancer in NAI's. 2 tables, 22 references.
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Colon Cancer Testing and Screening Source: Archives of Pathology and Laboratory Medicine. 123(11):1027-1029, November 1999. Summary: Colorectal carcinoma is the second most frequent cause of cancer deaths in the United States. The morphogenesis of the disease is well-defined, and a large number of risk factors have been identified. The accessibility and evident morphogenesis of colorectal neoplasia, in addition to the identification of inherited syndromes predisposing to the disease, have advanced the understanding of the molecular genetics and molecular pathology of this cancer. Molecular testing of tumors and patients has the potential to favorably affect patient outcome and accelerate the decline in death rates from colorectal cancer. Testing can be directed at several goals and make use of several specimen sources. The applications include use of molecular techniques to identify micrometastasis in sites of interest, or assessment of surrogate micrometastasis as evidence of hematogenous dissemination in organs where clinically important
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metastasis is rare. Molecular testing also has the potential to reveal the genetic and phenotypic characteristics of a tumor, which permits completion of the complex events needed for successful metastasis. Markers of this type could indicate the likelihood of recurrence after apparently curative surgery. A second area of testing of tumors is directed at identifying markers for later development of additional primary tumors, sometimes inappropriately referred to as recurrence. Testing of patients through fecal and blood specimens has broad potential to improve patient outcome. Diagnosis, surveillance, and screening for neoplasms could be enhanced by testing for mutations if various technical problems can be overcome and costs addressed satisfactorily. Clinical application of molecular testing is already underway in inherited syndromes. 3 tables, 18 references. ·
What Is the Optimal Strategy for Colon Cancer Surveillance in Patients With Ulcerative Colitis? Source: Cleveland Clinic Journal of Medicine. 66(5):273, 277, May 1999. Summary: The authors discuss colon cancer surveillance in patients with ulcerative colitis. The optimal colon cancer screening strategy regarding number of colonoscopies, interval between examinations, and biopsy protocol for patients with ulcerative colitis is unclear. The authors recommend that patients with ulcerative colitis undergo a colonoscopy every 1 to 3 years, and during these procedures, a biopsy should be taken every 10 centimeters (cm). If any of these biopsy samples reveals dysplasia, a total proctocolectomy should be performed. The authors make these recommendations because persons with inflammatory bowel disease have twice the risk of colorectal cancer as the general population, and the risk increases over time. A history of primary sclerosing cholangitis significantly adds to the risk of dysplasia and colorectal cancer in patients with ulcerative colitis. Biopsy samples should be taken every 10 cm because dysplasia can be present focally or diffusely. The authors recommend a total proctocolectomy after any dysplasia is found on biopsy because the risk of cancer is 19 percent in patients with low-grade dysplasia, and 42 percent in patients with high-grade dysplasia. The authors conclude that research is going to determine alternative markers of malignancy to improve the sensitivity of current surveillance strategies. 10 references.
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Physicians' Recommendations for Colon Cancer Screening in Women: Too Much of a Good Thing? Source: American Journal of Preventive Medicine. 15(3):246-249, October 1998. Summary: Researchers conducted a survey of community primary care physicians' recommendations for colorectal cancer (CRC) screening in women. They sent a postal questionnaire to 1,292 community-based primary care physicians throughout North Carolina in 1994, requesting information on demographics, thei r practice, and their recommendations for CRC screening for women using the fecal occult blood test (FOBT), flexible sigmoidoscopy (SIG), and colonoscopy (COL). Of the 545 completed questionnaires (42 percent) returned by physicians, 508 were analyzed. The responding physicians were generally male (82 percent) and white (93 percent). The largest proportion (42 percent) were general or family practitioners, and approximately 30 percent were in solo practice. Thirty-two percent practiced in nonmetropolitan areas, and 27 percent were age 55 or older. Seventy-two percent of the physicians, overall, reported that they needed more information on CRC screening and 58 percent reported at least some patient demand for CRC screening. Ninety-six percent of the physicians recommended FOBT, either alone or in combination with SIG or COL for women age 50 or older. Almost all (94 percent) reported recommending annual FOBT screening. Sixty-
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nine percent also recommended SIG. Of these, the most commonly recommended SIG screening interval was 5 years. Eighty-two percent of the respondents, overall, recommended annual FOBT screening for women younger than age 50, and 74 percent recommended annual FOBT screening for this group. Twenty-eight percent of the physicians recommended regular screening with SIG for women under age 50. The most common screening interval was every 3 to 5 years. SIG recommendation was higher among older physicians, solo practitioners, and physicians who said they needed more information on CRC screening. Nineteen percent of the respondents recommended COL for screening to any age group of women. Among those recommending COL, 90 percent also recommended FOBT and SIG. Only 10 percent included COL as part of a two-test strategy, combining it with FOBT or SIG. No physician adopted COL as a single screening procedure. Researchers concluded that the results of this survey suggest that in 1994, primary care physicians in North Carolina recommended earlier and more aggressive screening for CRC than that supported by national organizations or scientific evidence. While the opportunity to save lives through screening is appealing, too much of a good thing can divert resources away from other important health issues. 1 table, 11 references. ·
Diet and Risk of Colon Cancer in a Large Prospective Study of Older Women: An Analysis Stratified on Family History (Iowa, United States) Source: Cancer Causes and Control. 9(4):357-367, August 1998. Summary: Researchers analyzed data from a prospective cohort study to determine if dietary associations with colon cancer varied with family history of the disease. Investigators utilized data obtained in the Iowa Women's Health Study, a prospective study of 35,216 Iowa women based on a random sample of all women between age 55 and 69, who held a valid Iowa driver's license in 1986. A 1986 baseline questionnaire asked about lifestyle factors, reproductive history, prevalence of cancer, medical conditions or diseases, family history of selected malignancies, including colon cancer, and sociodemographic variables. Information on incident self-reported diseases and current residence was collected on the cohort through followup questionnaires mailed in 1987, 1989, and 1992. Researchers assessed diet using a semiquantitative food frequency questionnaire. Participants reported their current height and weight, and measured their waist and hip circumferences. Values of the body mass index and waist/hip circumference ratio were calculated from the anthropometric data. Classification of family history of colon cancer was based on the occurrence of the disease in fathers, mothers, sisters, and brothers as reported in the 1992 questionnaire. Colon cancer cases were identified through the Iowa State Health Registry, which were then matched to the study participants through computer linkage. The data were analyzed using the Cox regression technique. A total of 4,239 women had a positive family history of colon cancer, and 22,698 had no family history of colon cancer. The overall association of dietary components with colon cancer incidence was similar for women with and without a family history of the disease. Total calcium intake was significantly inversely associated with colon cancer incidence among women with a negative family history of the disease. Dietary calcium intake was not associated with colon cancer risk in those with a positive family history of the disease. Total vitamin E intake was also significantly associated with a lower colon cancer risk for women with a negative family history. Vitamin E intake was not significantly associated with colon cancer risk in women with a positive family history. High dietary intake of fiber, fruits, and vegetables were all weakly, inversely associated with colon cancer risk among women with a negative family history of the disease, but not among women with a positive family history. Researchers concluded that the associations of most dietary
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components with colon cancer were similar for women with and without a family history of the disease. A few differences were noted that, if corroborated, may affect dietary strategies for persons with a family history of colon cancer. Emphasizing high dietary intake of fiber, fruits, and vegetables may be a less-effective risk reduction intervention for persons with a family history of the disease. 4 tables, 41 references. ·
Primary Prevention of Colon Cancer With Dietary and Micronutrient Interventions Source: Cancer. 83(8, Supplement):1734-1739, October 15, 1998. Summary: The authors discuss the epidemiology of colorectal cancer (CRC) and the results of epidemiological studies evaluating the effects on CRC risk of (1) low-fat diet; (2) high-fiber diet; (3) low-fat/high-fiber diet and/or high fruit and vegetable diets; (4) diets high in antioxidant micronutrients, such as vitamin C, vitamin E, selenium, and beta-carotene; and (5) excess dietary consumption of calcium. The results of epidemiological studies investigating the effects of various dietary factors suggest that high levels of dietary fiber, fruits, vegetables, and calcium intake may slow the carcinogenic process. Data on the association between fat intake and CRC risk are equivocal. Experimental animal carcinogenesis studies have shown that high-fat intake increases the incidence of colon carcinomas. Most studies that have adjusted for total dietary energy intake have not shown a significant correlation betwee n fat consumption and CRC risk. Recent and ongoing clinical studies have focused on reducing the recurrence rate of colonic adenomas in patients with a prior history of resected adenomatous colonic polyps. The use of this intermediate endpoint, rather than CRC incidence, is associated with considerable cost and feasibility advantages. Currently, Phase III trials are underway to evaluate the effects of low-fat/high-fiber, fruit and vegetable, calcium, folate, and selenium-containing diets on colonic polyp recurrence rates. 1 table, 47 references.
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Dietary Risk Factors for Colon Cancer in a Low-risk Population Source: American Journal of Epidemiology. 148(8):761-774, October 15, 1998. Summary: Researchers examined the relationship between diet and colon cancer in a low-risk population. They based the study on the Adventist Health Study (AHS), a large prospective cohort study of health changes in 34,198 non-Hispani c white Seventh Day Adventists living in California, and others living in Adventist households in California. The AHS participants had completed a lifestyle questionnaire in 1976, for which they provided information on demographics, diet, physical activity, socioeconomic factors, and medical history. The dietary section of the questionnaire consisted of 55 semiquantitative food frequency questions. A meat index was determined from responses to six questions on the current frequency of consumption of specific meats (beef, pork, poultry, and fish), and one question on the current frequency of consumption of any meat. Dietary data were available for 32,051 respondents who had no previous history of cancer. The cohort was followed for 6 years, from 1976 to 1982, during which the incidence of colon cancer was determined by responses to annual mailed questionnaires and linkage to two population-based tumor registries operating in California. During the 6-year followup period, 157 colon cancer cases were diagnosed. Researchers evaluated associations between the dietary variables and colon cancer risk using Cox proportional hazard models that included covariates for (1) age, (2) sex, (3) body mass index (BMI), (4) parental history of colon cancer, (5) physical activity, (6) current smoking, (7) past smoking, (8) alcohol consumption, and (9) aspirin use. Consumption of total meat, red meat, and white meat at least once a week, versus no consumption, was significantly associated with an increased risk for colon cancer,
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relative risk s (RR's) being 1.85, 1.90, and 3.29, respectively. Legume consumption at least once a week, versus no consumption, was significantly, inversely associated wit h colon cancer risk, the RR being 0.53. Among males, a BMI greater than 25.6 kilograms per square meter (kg/m2) was significantly associated with an increas e in colon cancer risk when compared to men having a BMI below 22.5 kg/m2. Logistic regression analysis indicated a complex interaction in which subjects who had high red meat consumption, low legume consumption, and a high BMI experienced a more than threefold increase in colon cancer RR, compared to all other patterns based on these variables. This pattern of apparent risk factors was thought to contribute to increases in both insulin resistance (high BMI and high red meat intake) and glycemic load (low legume intake). If this association actually represented a causal relationship, this would implicate hyperinsulinemic exposure as playing a role in colon carcinogenesis. Researchers concluded that the overall findings in the AHS cohort indicate that intake of both red and white meat are important dietary risk factors for colon cancer, and further suggest that the increased risk due to red meat intake occurs only with lower legume intake and greater body mass. These associations raise the possibility that the risk due to meat intake is mediated by multiple mechanisms, one of which may involve red meat intake in a constellation of causal factors that produces higher plasma insulin levels. 3 figures, 4 tables, 90 references. ·
Colon Cancer Screening: Sigmoidoscopy or Colonoscopy Source: Gastrointestinal Endoscopy Clinics of North America. 7(3):365-386, July 1997. Summary: The authors discuss the use of sigmoidoscopy and colonoscopy for colon cancer screening. Most people with colorectal cancer do not have identified risk factors, so screening of asymptomatic people is recommended. Currently, several major health organizations recommend screening for colorectal cancer. This includes the fecal occult blood test (FOBT) every year and sigmoidoscopy every 3 to 5 years beginning at age 50 years (although some believe that a one-time colonoscopy at age 60 years may be more cost-effective). Most physicians accept FOBT as a standard of practice. FOBT is simple and convenient, but has several problems. For example, it is a poor test for colorectal neoplasms when used alone. The rigid sigmoidoscope has been used for screening rectosigmoid cancer for nearly 100 years, although flexible sigmoidoscopy is more acceptable to the patient. Strict research has not yet evaluated sigmoidoscopy for screening asymptomatic, average-risk people for prevention and early detection of colon cancer. However, some studies indicate it is an effective preventive screening method. There is controversy over how often to perform sigmoidoscopy, when to recommend it, and appropriate ages to start and stop. Colonoscopy remains the gold standard for visualization of the colon and detecting polyps that can lead to cancer. It can detect most neoplasms in over 90 percent of affected people. Its sensitivity is 95 percent, with a negligible false-positive rate. The estimated cost of colon cancer screening is well within the benchmark figure of $40,000 per year of life saved, which the government considers cost-effective. 4 tables, 113 references.
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Screening for Colon Cancer: Economics and Related Considerations Source: Seminars in Roentgenology. 31(2):170-176, April 1996. Summary: There are four widely available tests and examinations for the detection and diagnosis of colorectal cancer that are thought suitable for colorectal cancer screening: (1) Examination of the stool for occult blood, (2) flexible sigmoidoscopy, (3) barium enema, and (4) colonoscopy. A major consideration in the use of the Hemoccult test for screening is that it is susceptible to many false positive reactions from a variety of
22 Colon Cancer
substances including ingested meat, aspirin, and a number of vegetables. The major failure of testing for occult blood in the stool as a method of colorectal cancer screening is that the test suffers from an unacceptably low sensitivity. Flexible sigmoidoscopy is the most widely available and least costly of these examinations that physically inspect all or part of the colon and rectum. The major limitation is that most carcinomas of the colon are beyond the reach of the 60 centimeter instrument, as the examination is commonly performed. The barium enema examination provides the opportunity to physically examine the entire colon and rectum with an examination that is minimally invasive and is tolerable without sedation. The double contrast study should probably be favored over the single contrast technique because it is desirable to locate as many adenomatous polyps as possible so that they may be removed, thus removing their potential for developing into a carcinoma. This examination has the least risk of any of the examinations capable of visualizing the entire colon and rectum. Colonoscopy provides an alternative method and has several advantages: (1) Excellent sensitivity for lesions of al l sizes, and most of the time the entire colon is visualized; (2) an almost 100 percent specificity during screening; (3) allows biopsy of any malignant-appearing lesion, establishing its malignancy and cell type prior to surgery; and (4) most benign adenomas, when detected, can be removed during this diagnostic examination. To date, there has been no clinical comparison of the cost-effectiveness of the various strategies proposed for colon cancer screening. 17 references. ·
Population-based, Community Estimate of Total Colon Examination: The Impact on Compliance With Screening for Colorectal Cancer Source: American Journal of Gastroenterology. 97(2):446-451, February 2002. Summary: Researchers conducted a population-based survey of people in two Pennsylvania communities to investigate the prevalence of colorectal cancer screening and the impact of total colon examination (TCE), such as with colonoscopy, on screening compliance. They also assessed the accuracy of self-reported use of recent flexible sigmoidoscopy (FS), barium enema, or colonoscopy and investigated colorectal cancer testing history in relation to risk factor status (e.g., family history of colorectal cancer). The study involved interviews with 414 people age 50 to 79 years who had no histories of colorectal cancer or polyps. The respondents reported ever having had and duration since the last use of fecal occult blood testing (FOBT), FS, rigid proctoscopy, barium enema, and colonoscopy. Data analysis indicated that the prevalence of TCE in this group of people was significant. Including TCE significantly increased measured compliance with colorectal cancer screening. Overall, 18.7 percent of respondents with average risk of colorectal cancer used TCE with barium enema or colonoscopy within the previous 5 years. People with family histories of colorectal cancer reported testing with TCE at a higher rate. The researchers conclude that TCE may contribute significantly to overall testing for colorectal cancer within this population. 5 tables, 13 references.
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Case for Screening for Colorectal Cancer: A Preventable Disease Source: Delaware Medical Journal. 74(2):93-94, February 2002. Summary: The author presents a case for screening for colorectal cancer as a preventive measure. Colon cancer is the second leading cause of cancer deaths in the United States. Lifetime risk is estimated at 6 percent. About 140,000 cases of colon cancer are diagnosed annually in the United States and about half of these are at advanced stages at diagnosis. Despite these statistics, at least half of colorectal cancer cases are preventable. The American Cancer Society, the U.S. Preventive Services Task Force,
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gastrointestinal specialty societies, and the Agency for Health Care Policy and Research have all recommended colon cancer screening. About 70 to 80 percent of all colorectal cancers occur in average risk persons. Estimates are that colon cancer screening is more cost-effective than breast cancer screening and it is now covered by many insurers. Despite this, it is estimated that only 30 percent of patients eligible for screening are actually screened. Barriers to screening include (1) psychological and cultural barriers to discussing colorectal issues with physicians and (2) the perception that testing is painful and offensive. The author believes that greater patient and physician awareness is necessary. A preventive medicine flow sheet published in this issue of the Journal should make colon cancer screening easier for physicians to implement and track. 1 table, 9 references. ·
Noninvasive Colorectal Cancer Screening Source: Digestive Diseases and Sciences. 47(6):1236-1240, June 2002. Summary: Researchers investigated a technique of detecting abnormal mucin in fecal samples as a method of screening for colorectal neoplasia. Abnormal mucin with the sialylated-Tn epitope is produced by colorectal cancer cells and is immunologically distinguishable from normal colonic mucin. Colon-ovarian tumor antigen (COTA) isolated from LS174T tumor xenografts was used to produce a monoclonal antibody, SP21, with immunoreactivity identical to absorbed polyclonal antibody. In an immunohistochemical study with SP-21 monoclonal antibody, SP-21 stained several other cancer tissues. The relationship between COTA and SP-21 was established by chemical analysis of purified COTA, block of immunoreactivity by N-acetyl neurominic acid, and loss of immunoreactivity after neuraminidase treatment. The researchers assumed that goblet cells of colorectal cancer produce abnormal mucin with STn epitope. As this mucin is carried with the fecal stream, immunological detection of COTA in the fecal samples with SP-21 monoclonal antibody could be a method of screening for colorectal cancer. The researchers selected 100 patients with risk factors or signs of colon cancer who were scheduled for colonoscopic examination. The patients used a premailed kit to collect a fecal sample prior to the colonoscopy. The researchers extracted soluble glycoprotein from the fecal samples, performed a protein content assay, prepared a standard curve of COTA, and conducted a dot assay of COTA. In the dot assay, the researchers applied anti-COTA monoclonal antibody SP-21 to the samples and determined the optical density of each slot dot by an imaging densitometer. They determined quantitative values of samples from the standard curve of COTA. COTA values greater than 15 micrograms per milliliter were considered positive for neoplasia. Results showed that 5 of 6 colon cancers, 6 of 22 adenomas, 1 of 8 colitis cases, and 2 of 58 normal patients tested positive. The researchers conclude that COTA assay is sensitive and more specific than Hemoccult screening for colorectal cancer. 3 figures, 2 tables, 18 references.
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Colorectal Cancer Prevention: Prospects for the First Decade of the 21st Century (Editorial) Source: Preventive Medicine. 34(6):563-566, June 2002. Summary: The author discusses future prospects for colorectal cancer prevention. In the second half of the last century, colorectal cancer became the second most common cause of death from cancer in men in the United States. It has become a disease of the Western world. Familial colorectal cancer represent only 3 to 4 percent of all colon cancers currently diagnosed in the United States, with lifestyle factors having a large affect on the risk of developing colorectal cancer. A major advance in our understanding of colon
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cancer in the latter part of the last century was the description of the sequence of anatomic and genetic changes that occur during the process of carcinogenesis. Early detection of colorectal cancer involves the detection of overt malignancies and precancerous colorectal adenomas. Fecal occult blood testing, sigmoidoscopy, and colonoscopy, followed by polypectomy, are the most common methods of screening. Secondary prevention in the form of screening lowers cancer incidence and mortality and has led to national recommendations for colorectal cancer screening in high- and average-risk persons. However, few people are following these recommendations. Primary prevention methods include (1) dietary and lifestyle changes, (2) nonsteroidal anti-inflammatory drugs, (3) cyclooxygenase-2 inhibitors, and (4) calcium supplementation. Four issues for the future are to (1) detect those persons who are at increased risk for the development of colon cancer; (2) develop screening methods that are acceptable to the average-risk population, including improved fecal analysis and better indexes of mucosal epithelial cell abnormalities; (3) consider left and right colonic neoplasia as different entities requiring different methods of detection and prevention; and (4) consider the administration of pharmaceuticals or nutrients as approaches to prevention. 21 references. ·
Screening for Colorectal Cancer in Adults at Average Risk: A Summary of the Evidence for the U.S. Preventive Services Task Force Source: Annals of Internal Medicine. 137(2):132-141, July 16, 2002. Summary: Researchers summarize the evidence for the effectiveness of different colorectal cancer screening tests for adults age 50 years and older at average risk, including (1) digital rectal examinations (DRE's), (2) in-office fecal occult blood testing (FOBT) after DRE, (3) FOBT, (4) sigmoidoscopy, (5) FOBT and sigmoidoscopy in combination, (6) double-contrast barium enema (DCBE), and (7) colonoscopy. They used the Guide to Clinical Preventive Services, Second Edition, existing systematic reviews, focused MEDLINE searches from 1966 to September 2001, and hand searches of key articles to identify relevant literature. The researchers identified 56 relevant articles. Evidence from randomized trials supported the effectiveness of FOBT in reducing colorectal cancer incidence and mortality rates compared with no screening. Evidence from case-control studies supported the effectiveness of sigmoidoscopy and possibly colonoscopy in reducing colon cancer incidence and mortality rates. A nonrandomized, controlled trial examining colorectal cancer mortality rates and randomized trials examining diagnostic yield supported the use of FOBT combined with sigmoidoscopy. The literature on DCBE was unclear. The researchers conclude that (1) colorectal cancer screening reduces colorectal cancer incidence and mortality and (2) there is not enough evidence to determine the most effective colorectal cancer screening strategy. 2 tables, 66 references.
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Barriers to Screening for Colorectal Cancer Source: Gastrointestinal Endoscopy Clinics of North America. 12(1):145-170, January 2002. Summary: The author summarizes the rationale for screening for colorectal cancer (CRC) and discusses (1) evidence delineating barriers to CRC screening, (2) changes that must be implemented to overcome these barriers, and (3) implications for primary care practice in recommending CRC screening. Most Americans have not been screened for CRC despite high-quality evidence and a compelling rationale supporting screening. Less than 40 percent of adults over age 50 years report ever having had a colon screening test and less than 30 percent are up-to-date with CBC screening. Topics
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include (1) the lack of a systematic approach to prevention; (2) the key processes of primary care-based preventive care; (3) barriers to patients scheduling and arriving at visits to primary care clinicians; (4) barriers to physicians ordering colorectal screening at the time of the visit; (5) barriers to selecting fecal occult blood testing, flexible sigmoidoscopy, double contrast barium enema, and colonoscopy; (6) barriers to having patients follow through on recommended screens; and (7) recommendations. 97 references. ·
Correlates of Colorectal Cancer Screening Compliance and Stage of Adoption Among Siblings of Individuals With Early Onset Colorectal Cancer Source: Health Psychology. 21(1):3-15, January 2002. Summary: Researchers used concepts from the health belief, transtheoretical, and dual process models to assess the screening practices among siblings of individuals diagnosed with colorectal cancer (CRC) prior to age 56 years. The researchers recruited (1) 452 patients from oncology and surgical practices at four cancer centers and from surgical practice groups associated with nine hospital-based community practices in the northeastern United States and (2) 504 of their siblings. Criteria for inclusion were (1) diagnosis of colon or rectal cancer since 1995, (2) age less than 56 years at diagnosis, (3) no history of hereditary cancer syndrome, (4) no history of inflammatory bowel disease, and (5) ability to comprehend English. The researchers assessed (1) health history and practice, (2) affected sibling medical status, (3) CRC knowledge, (4) doctor and family member input, (5) psychological measures, and (6) CRC screening. Results showed that (1) 57 percent of the siblings were on schedule with CRC screening, (2) 3 percent never heard of CRC screening, (3) 14 percent were in the precontemplation stage for screening, (4) 5 percent were in relapse or at risk for relapse, (5) 23 percent were in the contemplation stage for screening, and (6) 6 percent were in the maintenance stage for screening. Nine correlates with CRC screening were (1) higher education, (2) compliance with regular dental care, (3) having a doctor recommendation for screening, (4) having physician and family support, (5) reporting fewer con's and more pro's of screening, (6) having higher perceived risk of CRC, (7) having a higher commitment to screening, (8) avoiding the health care system less, and (9) having a closer relationship with the sibling. Variables associated with stage of adoption were (1) education, (2) regular dental care, (3) medical insurance, (4) physician recommendation, (5) family recommendation, (6) physician support, (7) con's, (8) higher risk, (9) preventability of CRC, (10) commitment to screening, and (11) close relationship with sibling. The researchers conclude that these results are an early step in understanding decision making about CRC screening among family members at risk for CRC. 6 tables, 54 references.
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Screening for Colorectal Cancer: Recommendations and Rationale Source: American Journal of Nursing. 102(9):107-108, 111, 113-114, 117, September 2002. Summary: This statement summarizes the current United States Preventive Services Task Force (USPSTF) recommendations for screening for colorectal cancer (CRC). The statement (1) summarizes clinical considerations underlying the USPSTF recommendations, (2) updates the 1996 recommendations on this topic, and (3) presents recommendations by other organizations on CRC screening. The USPSTF found fair to good evidence that several methods are effective in reducing mortality from CRC. The USPSTF concluded that the benefits from CRC screening substantially outweigh potential harms, but the quality of evidence, magnitude of the benefit, and potential harms vary with each method. The USPSTF found good evidence that periodic fecal
26 Colon Cancer
occult blood testing (FOBT) reduces mortality from CRC and fair evidence that sigmoidoscopy (SIG) alone or in combination with FOBT reduces mortality. The USPSTF did not find direct evidence that screening colonoscopy (COL) is effective in reducing CRC mortality, due in part to the fact that COL is usually considered the criterion standard. COL was found to be effective for detecting cancer and large polyps. This efficacy of COL is supported by its role as the criterion standard in trials of FOBT, extrapolation from SIG studies, limited case-control evidence, and its ability to inspect the proximal colon. Double-contrast barium enema offers an alternative to COL for inspecting the entire colon, but it is less sensitive than COL and there is no direct evidence that it is effective in reducing mortality rates. The USPSTF found insufficient evidence that newer screening technologies, such as computed tomographic colography, are effective in improving health outcomes. There are insufficient data to determine which screening strategy is best in terms of the balance of benefits and potential harms or cost benefits. Studies reviewed by the USPSTF indicate that CRC screening is likely to be cost effective (less than 30,000 dollars per additional year of life gained) regardless of the strategy chosen. It is unclear, however, whether the increased accuracy of COL compared with alternative screening methods (such as identifying lesions that FOBT and flexible SIG would miss) offsets the procedure's additional complications, inconvenience, and costs. 31 references. ·
How Should We Screen for Colorectal Cancer? Source: Digestive Diseases and Sciences. 47(9):1982-1983, September 2002. Summary: The authors discuss a multicenter study that evaluated the prevalence of neoplasia and the sensitivity of one-time screening with a fecal occult blood test (FOBT) plus sigmoidoscopy for colorectal cancer. Researchers conducted the study at 13 Veterans Affairs medical centers from February 1994 through January 1997. Analysis was completed for 2,885 adults who had a complete examination of the colon to the cecum and returned FOBT test cards prior to colonoscopy. At least one test card was positive for fecal occult blood in the case of 239 subjects, 8.3 percent. Among all 306 subjects with advanced neoplasia, 73 (23.9 percent) had a positive test for fecal occult blood. This resulted in a sensitivity of 35.6 percent, a positive predictive value of 39.7 percent, and a negative predictive value of 87.8 percent. There was a strong association between the number of test cards with positive results and the likelihood of advanced neoplasia. In this study, 30.5 percent of the subjects with a positive test for fecal occult blood had advanced neoplasia, as compared with 8.8 percent of those with a negative test. Testing with one-time sigmoidoscopy alone would detect 70.3 percent of patients with advanced neoplasia. One-time combined testing would fail to identify 24 percent of the patients with advanced neoplasia. 7 references.
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Virtual Colonoscopy: A New Tool for Colorectal Cancer Screening Source: Current Opinion in Gastroenterology. 17(1):78-85, January 2001. Summary: The authors conducted a literature review on virtual colonoscopy as a screening tool for colorectal cancer, including the technique, image display, image reconstruction, clinical trial results, and feasibility. The basic technique of virtual colonoscopy involves (1) cleansing the patient's colon with standard barium enema or colonoscopy bowel preparation, colonic insufflation with room air or carbon dioxide, and (3) thin-section helical computer tomography (CT) of the abdomen and pelvis followed by computer manipulation of the CT dataset. Virtual colonoscopy requires a well prepared, cleansed colon to achieve appropriate sensitivity and specificity. CT scan acquisition usually involves the use of both supine and prone helical CT datasets to (1)
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help differentiate between mobile stool and fixed pathology such as cancers or polyps; (2) allow more even distention of the colon; and (3) improve visualization of segments of the colon obscured by intraluminal fluid. CT scanning usually takes less than 20 minutes. The radiation dose required for virtual colonoscopy is about 20 percent lower than the typical dose for double-contrast barium enema. After image acquisition, the CT data can be viewed using a variety of techniques, including (1) simple evaluation of the axial CT images at lung window settings, (2) reformatted two-dimensional images at cross-sectional and orthogonal planes to the long axis of the colon, (3) three-dimensional endoluminal-simulating conventional endoscopy images, and (4) extraluminal images that simulate barium enema images. Virtual endoscopy based on three-dimensional magnetic resonance imaging is also feasible and may be an alternative to CT. Preliminary results show that the accuracy of virtual colonoscopy for polyp detection exceeds barium enema and approaches conventional colonoscopy. The performance of virtual colonoscopy as a screening method has not yet been established. The authors conclude that (1) results of virtual colonoscopy studies are promising; and (2) if it proves to be an accurate, reliable, and cost-effective method for detecting polyps and early cancer, then it may improve population participation in screening programs and reduce the impact of colorectal cancer. 3 figures, 36 references. ·
Colorectal Cancer Screening: New Directions, Evolving Guidelines Source: Patient Care. 35(4):24-30, 33-34, February 28, 2001. Summary: The author reviews existing guidelines, recent study data, and the controversies concerning which screening options are best for colorectal cancer detection. While all individuals age 50 years and older should undergo screening for colorectal cancer, many primary care physicians report that they do not screen all eligible patients in their practice. Several options are offered to physicians and patients regarding colorectal screening and the physician and patient together should choose an appropriate screening regimen. Screening can prevent colorectal cancer through the detection and removal of precancerous polyps. Current views place an emphasis on total colon examination with colonoscopy in average-risk persons. Annual fecal occult blood testing combined with flexible sigmoidoscopy every 5 years is the most costeffective overall screening strategy available. Barriers to screening include patient unwillingness to discuss or have this part of the anatomy examined, physician's comfort level in discussing and performing colorectal screening, reimbursement, the economics of doing flexible sigmoidoscopy screening in the primary care office, and insufficient capacity to perform population-wide screening colonoscopy. 1 figure, 15 references.
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New Test May Be More Accurate in Detecting Precancerous Polyps and Curable Colorectal Cancers Source: Primary Care and Cancer. 21(3):14-16, March 2001. Summary: According to Dr. David Ahlquist, a new, noninvasive DNA test for detecting precancerous polyps and curable colorectal cancers was 91 percent sensitive for detecting cancer throughout the colon. The researchers believe that this test, although about 2 years away from becoming widely available for public use, could significantly change the way screening for colorectal cancer is done. This new test requires a stool sample and involves analyzing DNA that is shed from the surface of colorectal cancer tumors and excreted in the stool. Precancerous polyps and early-stage cancer yield specific DNA abnormalities. This new test measures these abnormalities and results in the high accuracy of detection. This test needs to undergo another phase of clinical trials. Meanwhile, Mayo Clinic physicians encourage people age 50 years and older to
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continue following their physician's advice and the current recommendations for screening. The researchers believe that this new DNA test may replace the fecal occult blood test that yields as many as 5 to 10 percent false-positive results. This new test also has several patient-friendly features: (1) Patients can provide stool samples at home using a special kit that fits on the toilet seat, (2) it requires no special dietary or medication restrictions, and (3) no bowel preparation is needed. This new DNA test has the potential to significantly reduce the morbidity and mortality of colorectal cancer. 1 figure, 1 reference. ·
Differing Attitudes Toward Virtual and Conventional Colonoscopy for Colorectal Cancer Screening: Surveys Among Primary Care Physicians and Potential Patients Source: American Journal of Gastroenterology. 96(3):887-893, March 2001. Summary: Researchers examined attitudes of primary care physicians and potential screening patients toward computed tomography colonoscopy (virtual colonoscopy) and conventional colonoscopy for colorectal cancer (CRC) screening. Investigators sent questionnaires by mail or E-mail to 1,000 physicians across the United States and 400 potential patients. Both questionnaires asked respondents about their preferences for virtual and conventional colonoscopy and the reasons for their preferences. Usable responses were received from 188 physicians (response rate 18.8 percent) and 323 potential patients (response rate 80.5 percent). On the basis of information about invasiveness, 76.6 percent of potential patients and 47.3 percent of physicians initially preferred virtual colonoscopy. When information about colon cleansing was given, the proportion of physicians and potential patients preferring virtual colonoscopy fell to 40.8 and 67.9 percent, respectively. When reminded that conventional colonoscopy, but not virtual colonoscopy, allows direct visualization of the colon, the proportion of physicians favoring virtual colonoscopy decreased further to 31.0 percent; however, the proportion of patients choosing virtual colonoscopy only dropped to 64.3 percent. When told that only conventional colonoscopy allows for the therapeutic intervention of polypectomy, the proportion of physicians favoring virtual colonoscopy dropped to 25.7 percent. The proportion of patients favoring virtual colonoscopy when given this information fell markedly to 47.0 percent. When informed that virtual colonoscopy does not require sedation, the proportion of physicians and patients favoring virtual colonoscopy rose to 51.6 and 67.4 percent, respectively. Across all questions, regardless of information provided, 60.2 percent of potential patients and 44.9 percent of physicians preferred virtual colonoscopy to conventional colonoscopy. Additionally, 82.3 percent of potential patients stated that they would comply more with recommendations for CRC screening and 61.7 percent of physicians would refer more patients for screening if virtual colonoscopy was available. Researchers conclude that potential patients preferred virtual to conventional colonoscopy, whereas physicians favored conventional colonoscopy. Physicians placed more importance on the ability of conventional colonoscopy to visualize the colonic mucosa directly and the opportunity for therapy. Potential patients were more encouraged than physicians by the availability of virtual colonoscopy to improve participation in CRC screening. 2 figures, 8 tables, 19 references.
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Colorectal Cancer: Not an Equal Opportunity Cancer (Editorial) Source: Gastroenterology. 120(4):1043-1046, March 2001. Summary: The author discusses racial and ethnic variations in colorectal cancer (CRC) incidence and mortality in the United States. The discussion focuses on two issues: (1) Why it is important to understand racial and ethnic variations in CRC incidence and
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mortality; and (2) why Americans of every race and ethnic group are not getting screened for CRC. The discussion specifically considers (1) CRC risk associated with race and ethnicity, (2) public perception and awareness of CRC, and (3) barriers to CRC screening. Rates of participation in screening are better if it is recommended by health care providers. The communication of risk of disease and benefits of screening to ethnic minorities may be especially ineffective. The process of risk communication to minorities has received little attention despite the fact that some groups suffer disproportionately from certain diseases. If there are race/ethnicity cultural barriers to colon screening, the author notes that one must study and understand these obstacles and develop appropriate educational tools. Important barriers to screening include lack of payment by insurers and lack of access to health care. The fact that a large proportion of the medically uninsured are black and fall into a higher risk group that is most likely to benefit from colon screening highlights the importance of finding a remedy for this problem. 21 references. ·
One-time Screening for Colorectal Cancer With Combined Fecal Occult-blood Testing and Examination of the Distal Colon Source: New England Journal of Medicine. 345(8):555-560, August 23, 2001. Summary: Researchers examined the effectiveness of one-time screening with the fecal occult blood test (FOBT) combined with examination of the distal colon by sigmoidoscopy (SIG) for detecting colorectal cancer (CRC). They recruited 3,121 asymptomatic patients seen at 13 Veterans Affairs centers between February 1994 and January 1997 for the study. The patients provided 3 consecutive days of stool samples on cards for FOBT testing; samples were rehydrated for interpretation. The patients then underwent colonoscopy (COL). Researchers considered examination of the rectum and sigmoid colon during COL as SIG. Of the 3,121 participants, 2,885 returned their FOBT cards before COL. The mean age of this group was 63.0 years, 96.8 percent were men, and 14.2 percent reported having a first degree relative with CRC. Results indicated that 1,319 participants (45.7 percent) had no polypoid lesions. In 472 (16.4 percent), the most advanced lesions were hyperplastic polyps or nonadenomatous polyps, and in 788 (27.3 percent), the most advanced finding was one or more tubular adenomas less than 10 millimeters in diameter. Advanced neoplasia was detected in 306 patients (10.6 percent). Of these, 182 had advanced neoplasia in the distal colon and 150 in the proximal colon. Altogether, 143 had one or more large tubular adenomas, 90 had an adenoma with villous features, 49 had an adenoma with high-grade dysplasia, and 24 had invasive cancer. Seventy-three patients (23.9 percent) with advanced neoplasia had a positive FOBT. When compared with patients who had a negative FOBT, the relative risk of advanced neoplasia in patients with a positive FOBT was 3.47. SIG identified 70.3 percent of all patients with advanced neoplasia. Combined one-time screening with FOBT and SIG identified 75.8 percent of patients with advanced neoplasia. Researchers conclude that one-time screening of asymptomatic persons with the FOBT plus SIG fails to identify about one quarter of those with advanced neoplasia and about half of those with advanced proximal neoplasia. Clinicians should not feel confident that advanced neoplasia can be ruled out when the results of one-time combined testing are negative. Screening programs that use FOBT plus SIG may be more effective if the tests are repeated at appropriate intervals. 4 tables, 21 references.
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Screening for Colorectal Cancer: Developing a Preventive Healthcare Program Utilizing Nurse Endoscopists Source: Gastroenetrology Nursing. 24(1):12-19, January-February 2001.
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Summary: The authors discuss screening for colorectal cancer (CRC) and the development of a CRC screening program incorporating nurse endoscopists at Northwestern Memorial Hospital (NMH), Chicago, Illinois. The program was developed and implemented during the creation of the Colon Cancer Screening Center (CCSC), a component of NMH's comprehensive gastrointestinal oncology program in 1997. The goals of the CCSC's CRC screening program were to (1) provide a unique early cancer detection program in the Chicago metropolitan area, (2) become a leader in early detection of CRC through screening, (3) provide a referral service to physicians within NMH that provides screening and preventive health education, and (4) develop a clinical database to track clinical outcomes and trends in patient compliance. The authors discuss aspects of developing the program that may be useful for other institutions interested in developing a similar program, including (1) the institutional marketing research process, (2) training nurse endoscopists and developing benchmark data to evaluate their training, (3) operational planning/advertising strategies, (4) implementing a program similar to the CCSC-based program, and (5) program evaluation. To date, 745 patients age 50 to 64 years old have been screened. Of these, 14 percent were referred for colonoscopy for multiple polyps or adenomas. One rectal carcinoma was identified. There were no complications from the procedures. 4 tables, 11 references. ·
Virtual Colonoscopy: A New Approach for Colorectal Cancer Screening Source: Gastroenterology Nursing. 24(1):5-11, January-February 2001. Summary: The author discusses virtual colonoscopy (VC) as a new approach for colorectal cancer (CRC) screening. The article (1) presents background information on CRC screening; (2) summarizes the American Cancer Society (ACS) guidelines for CRC screening; (3) discusses the various types of VC, including a summary of clinical studies of VC; (4) discusses safety issues of VC; (5) discusses the procedural aspects of VC; (6) discusses the advantages of VC relative to standard colonoscopy (SC); (7) summarizes the challenges of VC; and (8) considers future implications of CRC screening with VC. VC is a tomographic technique that can display computer images of the colon in an anatomical life-like format to facilitate image interpretation and improve diagnostic accuracy. There are three types of VC: (1) Computed tomography (CT) pneumocolonoscopy, (2) CT colography, and (3) VC. All three techniques use bowel cleansing, air insufflation, smooth muscle relaxation, and helical CT data acquisition. The differences between the procedures stem from the manner in which the data are manipulated. In CT pneumocolonoscopy, CT data are interpreted in the conventional radiologic manner. CT colography involves a CT of the colon in which a small section is examined and displayed in a two-dimensional image, supplemented with threedimensional images. VC is the interactive real-time navigation through the colon to simulate SC. Approximately 2,000 VC examinations have been performed worldwide. VC has been reported to have a sensitivity of 80 percent for detecting CRC and polyps greater than 10 millimeter. Its specificity has been reported to be 90 percent. An advantage of VC is that it does not require sedation. No perforations have been reported with VC. VC has the potential to examine the entire colon in substantially less time than SC. Although VC is comfortable for the patient, the patient still has to undergo a bowel preparation similar to that required for SC. The amount and time of insufflation, however, is less than that of SC, producing less discomfort for the patient. The author notes that VC appears to have tremendous potential for improving patient acceptance as a screening method for CRC. VC also appears to be an excellent method for implementing the current ACS guidelines for screening men and women at average risk for CRC beginning at age 50. 3 figures, 1 table, 39 references.
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Use of Colonoscopy to Screen Asymptomatic Adults for Colorectal Cancer Source: Gastrointestinal Endoscopy. 53(7):832-834, June 2001. Summary: The first two authors discuss the results of two large studies evaluating the reliability and accuracy of different methods of screening for colorectal cancer. The first study indicated that 2.7 percent of patients with no polyps in the portion of the colon distal to the splenic flexure had advanced proximal neoplasms. The other study found that a distal adenoma was not a reliable predictor of advanced proximal neoplasia; only 46 percent of patients with an advanced proximal lesion had a distal polyp that would have been detected by screening sigmoidoscopy. In another study on double contrast barium enema, only 48 percent of large adenomas found by colonoscopy were detected by barium enema. The authors conclude that the most accurate and reliable evaluation currently available is colonoscopy. In a response, Lieberman discusses issues of effectiveness, risk, cost, and resources that need to be considered before embracing colonoscopy as a primary screening tool. A response by Imperiale and Ransohoff indicates that they do not consider that the data from these studies justifies a recommendation for universal colonoscopy. Instead, the two studies should be scrutinized for strength and robustness, supplemented by an assessment of whether additional studies of colonoscopic screening are still needed. Information on risk factors should be used to stratify risk among those now considered average-risk persons. Colonoscopy could be extended to increased-risk persons, while its use among averagerisk persons could be deferred.
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Colorectal Cancer Screening in North Carolina: Community Clinicians' Perspectives Source: North Carolina Medical Journal. 62(5):292-297, September-October, 2001. Summary: Researchers conducted a survey to assess community clinicians' perspectives on colorectal cancer screening in North Carolina. Between November 1997 and May 1998, they sent a self-administered questionnaire to family practitioners, general practitioners, and general internists who were actively practicing in primary care settings. The questionnaire assessed (1) personal characteristics, (2) practices of colon cancer screening with fecal occult blood testing (FOBT) and flexible sigmoidoscopy (FS), and (3) attitudes toward and barriers to using FS. Of 1,333 physicians contacted, 736 (55 percent) provided usable responses. Results showed that (1) most respondents were male family practitioners in group practice; (2) 97 percent recommended periodic screening with FOBT; (3) of those recommending FOBT, 35 percent said that annual screening should start at age 50 years; and (4) 79 percent thought that the proper screening interval was once a year. Other results showed that (1) 92 percent recommended screening with FS, (2) 43 percent performed FS themselves, and (3) 85 percent agreed with recommendations that screening with FS should begin at age 50 years and be repeated every 3 to 5 years. Perceived barriers to FS differed according to respondents' experience with the procedure. Among practitioners who recommended FS but did not perform this procedure themselves, barriers included time constraints, equipment costs, inadequate reimbursement, and regulatory restrictions. Half of the respondents had received training in FS as medical residents. The most common perceived patient barrier to FOBT was inconvenience, and to FS was fear of pain and discomfort. The researchers conclude that there is a need to find ways to encourage physicians to promote colorectal cancer screening to their patients. 4 tables, 20 references.
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Knowledge, Beliefs, and Barriers Relevant to Colorectal Cancer Screening in an Urban Population: A Pilot Study Source: Family and Community Health. 24(3):34-47, October 2001. Summary: Researchers conducted a pilot study to assess the knowledge, beliefs, and barriers relevant to colorectal cancer (CRC) screening among working-class, predominantly minority men and women in New York City, New York. They interviewed 115 individuals age 53 years or older. The telephone interviews focused on six variables that could be changed through the Healthy Colon intervention: (1) Demographic and health characteristics, (2) CRC screening behaviors and intentions, (3) knowledge about CRC and CRC screening, (4) beliefs about CRC and CRC screening, (5) barriers to CRC screening, and (6) physician advice and social support for CRC screening. About one-third of participants were Hispanic and about 25 percent were black. Results showed that (1) 80.9 percent had had a recent general checkup; (2) 41.7 percent had recently been screened; (3) 27.8 percent had a fecal occult blood test (FOBT) within the past 2 years; (4) 10.4 percent had a flexible sigmoidoscopy within the past 5 years; (5) 22.6 percent had a colonoscopy within the past 10 years; (6) 58.3 percent were unscreened; and (7) of those unscreened, 38.8 percent intended to have an FOBT and 10.4 percent intended to have a flexible sigmoidoscopy within the next 6 months. Other results showed that (1) 87 percent had heard of CRC, but only 46.1 percent knew that there was a screening test for it; (2) 47.0 percent believed that CRC might affect them; (3) only 36.5 percent reported believing that their physician wanted them to perform an FOBT; and (4) active outside encouragement within the past 5 years was the only variable significantly related to screening status. The researchers conclude that (1) these participants had many inaccurate beliefs about CRC and CRC screening and (2) the low rate of CRC screening among these participants implies that CRC is not being discussed and FOBT is not being offered by physicians. 6 tables, 25 references.
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Screening Is Key to Preventing Colorectal Cancer Source: Business and Health. 19(6):40, June 2001. Summary: The author discusses cancer of the colon and rectum (colorectal cancer). Although it is the second leading cause of cancer-related deaths in the United States, it is also one of the most preventable. The key to prevention is to encourage and enable people age 50 years and older to get screened routinely. The risk for the disease increases with age. Routine screening of this age group is particularly important because three out of every four colorectal cancers occur in average-risk people with no known risk factors for the disease. People who have colorectal polyps or early-stage colorectal cancer usually have few or no symptoms initially. Many cases of and deaths from colorectal cancer can be prevented by screening for and removing colorectal polyps and by detecting and treating the cancer in its early stages. Several organizations recommend regular screening of all average-risk adults over age 50 years using a combination of the fecal occult blood test every year and flexible sigmoidoscopy every 5 years, total colon examination by colonoscopy every 10 years, or double-contrast barium enema every 5 to 10 years. Employers can (1) ensure that employee health insurance covers routine screening with minimal or no copayments; (2) offer flexible work schedules to facilitate use of preventive health services; (3) encourage employees to use preventive health services by providing educational materials, intra-office e-mails, or reminders in employee paycheck envelopes; and (4) arrange for worksite wellness programs to help employees lower cancer risk through increased physical activity, nutritional food choices, and appropriate weight loss.
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Quarter Century of Colorectal Cancer Screening: Progress and Prospects Source: Journal of Clinical Oncology. 19(18s):6s-12s, September 15, 2001. Summary: The author discusses the progress of colorectal cancer screening in the past 25 years. In 1967, it was shown that fecal occult blood testing (FOBT) could be used to screen for colorectal cancer. In the mid-1970's, the flexible sigmoidoscope was introduced. For the first time, the entire rectosigmoid could be examined comfortably. These two screening tests would be of little value without an accurate diagnostic test to examine the entire colon and find early-stage cancers and premalignant polyps. Colonoscopy, first introduced in 1970, provided this examination. Colonoscopy became a brief, efficient examination with a very low complication rate and with patient comfort. The concept that colorectal cancer evolves from the precursor lesion, the adenomatous polyp, has been accepted since 1928. The National Polyp Study began in 1978 and showed that a long period of time passes between the appearance of polyps in the colon and their progression to cancer. The 10-year polyp dwell time is critical because it provides a long window of opportunity for effective screening. Most patients who will develop colorectal cancer are at average risk with no special risk factors. People with increased risk are those who have (1) inflammatory bowel disease, (2) familial adenomatous polyposis, (3) hereditary nonpolyposis colorectal cancer, and (4) a family history of one or two close relatives with cancer. Colorectal cancer mortality has been shown to be reduced 30 to 40 percent with flexible sigmoidoscopy. Colorectal cancer screening guidelines recommend that average-risk men and women who are age 50 years and older, or who are age 40 years and older with a family history, should be screened by either FOBT or flexible sigmoidoscopy every 5 years or a combination of the two. Screening rates for colorectal cancer are low. The American Cancer Society's objectives are that (1) by 2005, 75 percent of people will be aware of colorectal cancer screening, and 60 percent will get screened; and (2) by 2015, there will be a 40 percent incidence reduction in colorectal cancer and a 50 percent mortality reduction. The author concludes that there are new colorectal cancer screening technologies currently being developed, but the technology exists today to substantially reduce the mortality of colorectal cancer and to prevent it. 4 figures, 5 tables, 27 references.
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Colorectal Cancer Screening: The Old and the New Source: Texas Medicine. 97(2):46-48, February 2001. Summary: In this special issue on what primary physicians need to know about cancer, the author (1) explains the serious health threat of colorectal cancer, (2) promotes routine colorectal cancer screening, and (3) discusses various screening methods. Most colorectal cancers and most deaths from colorectal cancer are preventable through screening. Colorectal cancer is well suited for screening because (1) it is common; (2) it has serious consequences; (3) it has a detectable asymptomatic phase; (4) acceptable, safe, and affordable screening procedures are available; and (5) early detection and treatment lead to decreased morbidity and increased survival. Colorectal cancer's long preclinical phase of 7 to 12 years affords clinicians the opportunity to intervene before it becomes incurable. Once colorectal cancer does develop, it takes an additional 2 years to pass through Duke's A stage. Colorectal cancer can be prevented through the detection and removal of adenomatous polyps. Fecal occult blood testing (FOBT) is the only screening method proven to decrease mortality from colorectal cancer, but it has limitations. Flexible sigmoidoscopy has been shown to complement FOBT and lead to a decrease in colorectal cancer mortality by being used to identify cancers within the rectum and distal colon. Colonoscopy is now being considered as a screening tool for colorectal cancer. It is the gold standard for detecting and removing polyps. The
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American College of Gastroenterology recently endorsed colonoscopy every 10 years as the preferred strategy for colorectal cancer screening in patients at average risk. Doublecontrast barium enema is also a screening tool for colorectal cancer, but it has never been studied in randomized trials, and it has low sensitivity. Virtual colonoscopy is an exciting new method of detecting colorectal adenomas that holds promise as a screening method. The author concludes that (1) colorectal cancer screening works well; and (2) colonoscopy is the most effective screening method, but it will remain controversial because of cost issues. 15 references. ·
Colorectal Cancer Screening: Keeping the Options Open (Editorial) Source: Effective Clinical Practice. 4(1):39-41, January-February 2001. Summary: The author discusses the pros and cons of various colorectal cancer screening methods. Research has shown that both fecal occult blood testing (FOBT) with colonoscopic followup and sigmoidoscopy reduce colorectal cancer mortality. Evidence for the effectiveness of the two other available screening approaches, colonoscopy and double-contrast barium enema (DCBE), is less direct. Colonoscopy is more sensitive than sigmoidoscopy because the colonoscope can be used to view the entire colon. The goal of FOBT is to make colonoscopic screening more efficient by identifying those most likely to benefit from colonoscopy. The evidence for DCBE is limited to descriptive studies showing that it has high sensitivity when compared with endoscopy for cancer or larger adenomatous polyps. It is possible that DCBE combined with colonoscopic followup could also provide benefit. The author believes that it is important to be open to all colorectal cancer screening methods because there is uncertainty about the relative benefits and risks of the available screening approaches. The author concludes that (1) we are fortunate to have several effective strategies for colorectal screening because it gives alternatives to patients and to primary care physicians; (2) until one screening method is shown to be superior to the others, all methods should remain available; and (3) the search for the optimal screening approach should continue. 1 table, 23 references.
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Colorectal Cancer in Women: An Equal Opportunity Disease Source: Journal of the American Osteopathic Association. 101(12, Part 2):S7-S12, December 2001. Summary: The authors discuss colorectal cancer (CRC) in women, including (1) general risk factors for CRC, (2) CRC risk factors unique to women, (3) CRC during pregnancy, (4) CRC screening guidelines, (5) recommendations for screening in people at average risk for CRC, (6) screening recommendations for people at increased risk, (7) treatments for CRC, (8) followup colonoscopy for CRC, (9) Duke's system for assessing 5-year survival rates for CRC, and (10) prevention of CRC. The incidence of CRC is similar in both men and women, but women have a higher prevalence of right-sided tumors and polyps. CRC risk factors are age, family history of CRC or polyps, personal history of colon cancer, polyps or inflammatory bowel disease, and a history of prior pelvic radiation therapy. CRC risk factors unique to women include gynecologic cancers, such as ovarian and endometrial cancers. More than 80 percent of CRC's in pregnant women occur in the rectum, in contrast to 31 percent in the general population. Although the symptoms of CRC in pregnant women are the same as in nonpregnant women, the symptoms of CRC are often overshadowed by the symptoms of pregnancy, which presents a major problem in diagnosis. CRC screening is recommended in asymptomatic women at average risk starting at age 50 years. For women at increased risk, it is recommended that CRC screening begin at age 40. The article also contains checklist summaries that address the following topics: (1) Summary of epidemiologic facts
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concerning CRC in women,(2) risk factors for the development of CRC, (3) the characteristics of CRC, (4) the Amsterdam criteria for hereditary nonpolyposis CRC, (5) symptoms and signs of CRC, and (6) factors that protect against CRC. 6 figures, 31 references. ·
Introduction: Rational for Colorectal Cancer Screening Source: Seminars in Ultrasound, CT, and MRI. 22(5):397-399, October 2001. Summary: The author provides an introduction to a series of papers on virtual colonoscopy (VC) and other imaging-based techniques for colorectal cancer (CRC) screening. A large number of randomized multicenter clinical trials have shown that CRC screening can reduce CRC mortality by 30 to 50 percent in asymptomatic averagerisk adults. The principle is to detect and remove small asymptomatic colonic adenomas before they can develop into carcinomas. A number of CRC screening techniques are available including fecal occult blood testing, flexible sigmoidoscopy, barium enema, and conventional colonoscopy. These have been used and studied in many different combinations, testing intervals, and strategies. Considerable debate persists as to the optimal test, test strategy, or timing interval among the various options. At present, guidelines from most major public agencies recommend a flexible multioption approach for the patient or physician without expressing a clear preference for any single strategy. Two additional problems hinder implementation of CRC screening programs for large populations based on existing tests and test combinations: (1) The natural history of polyps and (2) compliance. Although it is accepted that CRC's arise from preexisting adenomatous polyps, adenomatous polyps are extremely common with advancing age. It is not possible to select and predict which polyps will progress and evolve into frank carcinoma. Compliance problems arise because of the failure of the general public to submit to the admittedly embarrassing and/or unpleasant procedures required for CRC screening. VC has emerged as a safe, fast, highly accurate method for detecting colorectal polyps and neoplasms. VC promises to become an important new initiative for performing a full structural examination of the colon in CRC screening programs. Problems still face the radiology community in introducing this new technique, including the lengthy time required for data analysis, radiation doses from computed tomography screening, and the discomfort from colon preparation. Preliminary results of VC trials show VC can detect 80 to 90 percent of polyps greater in size than 1 centimeter.
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Colorectal Cancer Screening and Surveillance Source: Clinics in Colon and Rectal Surgery. 14(4):359-367, 2001. Summary: The author reviews the literature concerning the use of colonoscopy to prevent the development of colorectal cancer and provides recommendations for its implementation in various clinical scenarios. Colonoscopy is highly effective in screening average- and high-risk populations as well for surveillance in those with a prior history of colorectal polyps, cancer, or chronic colitis. Screening colonoscopy has been shown to be safe and important in detecting polyps and cancers that would have gone undetected had traditional screening measures been employed, and it appears to be cost-effective. Colonoscopy with polypectomy leads to a greater than 75 percent reduction in colorectal cancer development when compared with historical controls. Surveillance intervals for patients with a history of adenomatous colon polyps can be extended to at least 3 to 5 years under most circumstances. Colonoscopy following curative colorectal cancer surgery should follow typical postpolypectomy recommendations given the major goal of preventing a second primary colorectal cancer
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in this group. More research is needed to better stratify individual risk based on personal risk factors, colonoscopic findings, age, comorbid medical conditions, and possible genetic factors to individualize surveillance intervals and techniques. Identifying individual risk factors would allow colonoscopies to be allocated to those who have not yet undergone the procedure where the potential for identifying significant lesions is greatest. There is also a need for additional well-trained endoscopists to satisfy the expected rising demand for screening colonoscopy and the volume of surveillance examinations that will arise from this. 1 table, 38 references. ·
Colorectal Cancer: Prevention and Screening Source: Medsurg Nursing. 9(1):9-13, 20, February 2000. Summary: The author provides an educational activity for nurses and other health professionals who care for and educate patients regarding colorectal cancer. Colorectal cancer is a malignant growth from the lining of the colon and rectum that can penetrate the wall of the colon and invade the lymph nodes or spread to other organs. Symptoms of colorectal cancer may be (1) abdominal cramping or constant pain; (2) iron deficiency anemia; (3) partial or complete bowel obstruction; (4) change in bowel habits that lasts a few days; (5) weakness, fatigue, and jaundice; and (6) blood in the stool. Risk factors for colorectal cancer include (1) adenomatous polyps, (2) diets low in fiber and high in animal fat, (3) personal history, (4) family history, (5) familial adenomatous polyposis, (6) chronic ulcerative colitis, and (7) hereditary nonpolyposis colorectal cancer. Screening methods for colorectal cancer include (1) colonoscopy, (2) fecal occult blood testing (FOBT), (3) sigmoidoscopy, (4) double-contrast barium enema, and (5) digital rectal examination (DRE). Most people at average risk for colorectal cancer can begin routine screening at age 50. People at high risk should begin screening at puberty. Screening guidelines for asymptomatic persons are (1) DRE annually, (2) FOBT annually, (3) flexible sigmoidoscopy every 5 years, and (4) total colon examination by colonoscopy or barium enema with proctosigmoidoscopy every 5 to 10 years. Persons at high risk should consider shorter screening intervals and genetic testing. 1 table, 13 references.
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Update on Colorectal Cancer Source: American Family Physician. 61(6):1759-1770, March 15, 2000. Summary: Physicians present updated information on the pathogenesis and diagnosis of colorectal cancer (CRC). They discuss (1) the epidemiological aspects of CRC in the United States, (2) the association between polyps and CRC, (3) inflammatory bowel disease and CRC, (4) genetic factors and CRC, (5) staging of CRC and survival, (6) symptoms of CRC, (7) prevention of and screening methods for CRC, and (8) screening guidelines for CRC. An estimated 129,400 new cases of CRC occurred in the United States in 1999. The lifetime risk of developing CRC is 2.5 to 5 percent in the general population, but two to three times higher in persons who have a first-degree relative with colon cancer or an adenomatous polyp. Seventy to 90 percent of all CRC's arise from adenomatous polyps, whereas only 10 to 30 percent originate from sessile adenomas. Tumors or polyps that develop proximal to the splenic flexure have a poorer prognosis than those that arise more distally, due in part to a delayed diagnosis resulting from a later development of symptoms. Screening methods include digital rectal examination, fecal occult blood testing, rigid sigmoidoscopy, flexible sigmoidoscopy, double-contrast barium enema, and colonoscopy. A number of organizations have proposed CRC screening guidelines that vary in their
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recommendations. Most agree, however, that screening should begin at age 50 in persons without a personal or family history of CRC. 1 figure, 5 tables, 31 references. ·
Fighting Colorectal Cancer: A National Priority (Editorial) Source: Journal of Women's Imaging. 2(4):152-153, November 2000. Summary: The United States Surgeon General notes that more women than men will be diagnosed with colorectal cancer this year. He stresses that although mortality rates for women with colorectal cancer have declined over the past 20 years, but stresses that more needs to be done. Alarmingly, screening for colorectal cancer still lags behind other cancer screening and is a profoundly important public health issue. When diagnosed at an early, localized stage, more than 90 percent of patients survive 5 or more years after diagnosis. Once in a regional stage, only 64 percent of the patients survive 5 or more years. At an advanced stage, only 7 percent of the patients survive beyond 5 years. The role of the federal government is to assist in promoting screening for this potentially deadly cancer. Current screening procedures for all average-risk adults age 50 or more include annual fecal occult blood test, flexible sigmoidoscopy every 5 years, and total colon examination by colonoscopy every 10 years or double contrast barium enema every 5 to 10 years. It is hoped that public and private efforts to promote screening will increase in response to the Healthy People 2010 objectives.
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Effect of Fecal Occult-blood Screening on the Incidence of Colorectal Cancer Source: New England Journal of Medicine. 343(22):1603-1607, November 30, 2000. Summary: Researchers followed the participants in the Minnesota Colon Cancer Control Study for 18 years to determine the effect of screening on the incidence of colorectal cancer. Participants included 46,551 people enrolled between 1975 and 1978, and randomly assigned to annual screening, biennial screening, or usual care. Most participants were 50 to 80 years of age. Those assigned to the screening groups were asked to prepare and submit two samples from each of three consecutive stools for guaiac-based testing. Those with at least one positive slide in the set of six were offered a diagnostic examination that included colonoscopy. Screening was conducted between 1976 and 1982 and again between 1986 and 1992. Study participants have been followed with respect to newly-diagnosed cases of colorectal cancer and deaths. Followup has been more than 90 percent complete. During the 18-year period, 1,359 new cases of colorectal cancer were identified, 417 in the annual screening group, 435 in the biennial screening group, and 507 in the control group. The cumulative incidence ratios for colorectal cancer in the screening groups as compared with the control group were 0.80 and 0.83 for the annual screening and biennial screening groups, respectively. For both screening groups, the number of positive slides was associated with the positive predicative value both for colorectal cancer and for adenomatous polyps at least 1 centimeter in diameter. The researchers conclude that the use of either annual or biennial fecal occult blood testing significantly reduced the incidence of colorectal cancer. 1 figure, 2 tables, 33 references.
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Best Screening Test for Colorectal Cancer: A Personal Choice (Editorial) Source: New England Journal of Medicine. 343(22):1641-1643, November 30, 2000. Summary: The author discusses selection of the best screening test for colorectal cancer, and the basis for the choice. Fecal occult blood screening is the only test shown in randomized trials to lower mortality from colorectal cancer. Trials of screening with sigmoidoscopy are under way, but case-control studies currently provide the only
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evidence that sigmoidoscopy lowers mortality. No direct evidence proves that wholebowel screening reduced mortality, although studies of this topic are in process. Colonoscopy detects more proximal disease than does sigmoidoscopy. Selecting only on the basis of accuracy indicates that colonoscopy wins. It enables inspection of the entire colon, detection of almost all important neoplasms, and immediate polypectomy. Some stress magnitude of benefit over accuracy. By one estimate, 1,173 persons must undergo fecal occult blood screening to prevent one death in 10 years. Concern about harms might seem unwarranted, given the safety of colonoscopy and sigmoidoscopy, with bleeding or perforation occurring in only 10 to 30 persons in 10,000 examinations and death occurring in 1 per 10,000 colonoscopies. However, the probability of benefit is also small. For health insurers, costs dictate test preferences, but affordability depends on charges, which vary locally according to volume, market pressures, and contracts. For most patients, adverse effects that are more subtle than bleeding and perforation but far more common include (1) discomfort, embarrassment, and inconvenience associated with bowel preparation and the examination itself; (2) anxiety over negative consequences; and (3) harms resulting from false positive results. Sixty percent of eligible persons in the United States have never been screened for colorectal cancer. The author concludes that allowing patients to select the tests they prefer may do more good, as long as they choose something. 19 references. ·
Incidence Trends for Colorectal Cancer in California: Implications for Current Screening Practices Source: American Journal of Medicine. 109(4):277-281, September 2000. Summary: Researchers analyzed incidence trends for colorectal cancer (CRC) in California. They used data in the 1999 California Cancer Registry to identify all cases of CRC reported to the registry from 1988 to 1996 and their distribution in the colon. Multivariate analyses were used to examine the effects of age, sex, and race on tumor location over time. Overall, men were more likely to have left-sided (distal) tumors than were women (59 versus 51 percent), whereas black patients were less likely to have had left-sided tumors than were the other racial groups (48 versus 55 percent). By 5-year groups, the greatest incidence of cases occurred in those age 70 to 74 years. Up to and including this age, greater proportions of tumors were detected on the left side, whereas right-sided tumors predominated in the two oldest age categories (80 to 84 years and 85 years and older). These differences in anatomic location were statistically significant when univariate analyses were applied to the data. The annual incidence of CRC decreased by 19 percent from 1988 to 1996, from 200.2 to 162.4 cases per 100,000 persons. During the same period, downward trends were observed in the incidence of both left and right-sided cancers. On a percentage basis, the decrease in the incidence of leftsided cancers was approximately twice that seen on the right (24.3 versus 11.6 percent). This difference in the decrease in cancer rates by side was significant when adjusted for age, sex, and race. Researchers conclude that the incidence in CRC in California is decreasing, particularly for left-sided cancers. This decrease may reflect increased use of screening sigmoidoscopy. This trend has important implications for screening strategies. Current screening recommendations that emphasize examination of the distal colon may need to be expanded to include the entire colon, requiring the more frequent use of colonoscopy. 4 tables, 30 references.
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Explaining Recent Declines in Colorectal Cancer Incidence: Was It the Sigmoidoscope? (Editorial) Source: American Journal of Medicine. 109(4):332-334, September 2000.
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Summary: The author discusses possible reasons for the decrease in colorectal cancer incidence seen among California residents reported in a study published in this issue. The study found a substantial decrease in cancer between 1988 and 1996 and that the decrease is twice as great for distal cancers (those of the rectum, rectosigmoid, and sigmoid colon) than for the proximal colon. The authors of the study suggested that this pattern of decrease could be due to screening, particularly with flexible sigmoidoscopy, which was introduced into practice around 1980 and can lower colorectal cancer incidence by the detection and removal of premalignant adematous polyps, primarily in the distal colon and rectum. A similar decrease in colorectal cancer incidence has been seen nationally beginning abruptly in 1985 and, as in California, being greater for leftsided than for more proximal cancers. The abrupt decrease has been observed for each anatomic subsite within reach of the 60-centimeter flexible sigmoidoscope, but for no area above its reach. The editorial notes that since screening for colorectal cancer is not still widely practiced in the United States, the observed decreases in incidence could reflect other factors, such as environmental or behavioral factors. There is no evidence of changes so abrupt or substantial in any environmental or behavioral factor that could predict the rapid and substantial decrease that has been seen. Sigmoidoscopy screening, therefore, remains the most plausible explanation for the steep decrease in incidence. Regardless of its explanation, the decrease in distal cancers means that an increasing fraction of all colorectal cancers will originate in the proximal colon in coming years and, therefore, be less susceptible to detection by sigmoidoscopy. Until suitable approaches that can screen the entire colon have been identified, sigmoidoscopy is a safe, acceptable, and effective screening tool that is covered by essentially all insurers and appears to have contributed to an important reduction in CRC incidence during the past 15 years. 6 references. ·
Recommending High-fiber Diets to Prevent Colorectal Cancer Source: Medicine and Health/Rhode Island. 83(8):259-260, August 2000. Summary: The author discusses the issue of whether health professionals should recommend a high-fiber diet to prevent colorectal cancer. Since 1971, dietary fiber has been recognized as a modifiable risk factor for the prevention of colorectal cancer. However, since January 1999, three studies have been published that found no link between high-fiber diets and colon cancer. In the Nurse's Health Study, Fuchs and others looked at the relation between dietary fiber consumed by about 88,000 women over a 16-year period and their experience with colorectal cancer and adenomas. They surprisingly found a positive association between higher intakes of vegetables and the development of colorectal cancer. Two studies published in April 2000 also found no relation between dietary fiber and colorectal cancer. One study involved a low-fat, highfiber diet, and the other involved a high-fiber supplement. The author believes that, despite these results, the jury is still out. The American Institute for Cancer Research conducted a thorough review of over 4,500 studies and concluded that as many as three in every four cases of colon and rectal cancers could be prevented with healthy diets, that include fruits, vegetables, and whole grains. The Harvard Report on Cancer Prevention, Volume Three: Prevention of Colon Cancer in the United States concluded that the link between diet and colorectal cancer is inconclusive. Dietary and lifestyle factors that may be associated with an increased risk of colorectal cancer include (1) high levels of red meats and other animal sources in the diet, (2) obesity, (3) alcohol consumption, and (4) tobacco use. Dietary and lifestyle factors that may be associated with a decreased risk of colorectal cancer include (1) physical activity, and (2) dietary folic acid and folic acid supplements. Although the benefits of a high-fiber diet on the prevention of colorectal cancer is uncertain, high-fiber diets do have known health
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benefits. The author concludes that health professionals should continue to advise their patients to eat a high-fiber diet of fruits, vegetables, and whole grains to prevent chronic diseases, maintain overall health, and prevent obesity. 2 tables, 9 references. ·
Double-contrast Barium Enema for Colorectal Cancer Screening: A Review of the Issues and a Comparison With Other Screening Alternatives Source: American Journal of Roentgenology. 174(6):1529-1537, June 2000. Summary: The author reviews the issues regarding double-contrast barium enema (DCBE) for colorectal cancer screening and compares this procedure with other screening alternatives. Any colorectal cancer screening method that detects lesions before clinical presentation should be appropriate if it can be performed at intervals that result in acceptable expense or morbidity reduction. The strongest evidence for colorectal cancer screening comes from randomized controlled trials using fecal occult blood tests (FOBT's). Evidence of mortality reduction for sigmoidoscopy has been derived from case-control studies. In theory, performing FOBT's and sigmoidoscopy should be supplementary, but no studies have shown improved mortality reduction when the techniques have been combined. No studies have confirmed mortality reduction from screening colonoscopy in either average or high-risk persons. The strongest support for DCBE is based on the observation that treatment of early cancer in asymptomatic persons lowers disease-specific mortality and the removal of adenomatous polyps reduces cancer incidence. The DCBE compared to other colorectal screening methods reveals the most malignant and premalignant lesions. The true impact of a screening test is a function of its use in a continued implementation of an entire screening program. Few published cost-effectiveness analyses of colorectal cancer screening have assessed the full gamut of reasonable strategies for average-risk persons. Most of the financial burden from screening is generated by surveillance. No best test for colorectal cancer screening exists. Advocates of FOBT, sigmoidoscopy, or both emphasize the costs and morbidity reduction of colonoscopy, and advocates of colonoscopy emphasize the diagnostic limitations of FOBT and sigmoidoscopy. However, the DCBE offers the positive features of FOBT, sigmoidoscopy, and colonoscopy. DCBE is as safe or safer than flexible sigmoidoscopy, and it has comparable costs, provides a complete screening of the entire colon, and has a potential sensitivity similar to that of colonoscopy. The author concludes that DCBE maximizes the identification of high-risk patients while minimizing expense and morbidity. 3 figures, 111 references.
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CT Colonography for Colorectal Cancer Screening: Lessons from Mammography Source: American Journal of Roentgenology. 174(6):1539-1541, June 2000. Summary: The author discusses the lessons that can be learned from efforts with mammography that will be useful in introducing computed tomography (CT) colonography for colorectal cancer screening. Just as mammographers have become experts in all aspects of breast disease and the available therapies, radiologists trying to introduce CT colonography must familiarize themselves with the epidemiology, biology, and natural history of colorectal polyps and cancers to facilitate discussion with colleagues. Radiologists must (1) learn the screening recommendations provided by major health organizations; and (2) study the importance of risk stratification profiles, cost-benefit models of colorectal cancer screening, and research initiatives in colorectal cancer detection. Radiologists must understand the strengths and weaknesses of all of the colorectal cancer screening tests to propose CT colonography as a screening strategy. Organizations such as the American College of Radiology should assure that CT
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colonographers are competent. The issue of radiation dose reduction for CT colonography will be a major concern. A standardized, simplified screening CT colonographic examination will need to evolve to gain wide acceptance. CT colonography appears to have better specificity than mammography. Patient compliance has been a major problem with colorectal cancer screening. CT colonography still requires a standard colon cleansing preparation, but the procedure itself is less risky and time-consuming than colonoscopy and less uncomfortable than air-contrast barium enema. If the public is educated on these attributes of CT colonography, then more patients may undergo this type of colon screening. CT colonography must be affordable and reimbursable. Special interest groups in favor of colon screening and the potential of CT colonography as a new technique are emerging. The author concludes that radiologists should be prepared to lead colorectal cancer programs if and when CT colonography contributes to colorectal cancer prevention. 12 references. ·
Cost-effectiveness of Screening for Colorectal Cancer in the General Population Source: Journal of the American Medical Association (JAMA). 284(15):1954-1961, October 18, 2000. Summary: Researchers performed a cost-effectiveness (CE) analysis of screening for colorectal cancer (CRC) in the general population. They developed a state transit model to simulate the evolution of normal colonic epithelium to adenomatous polyp to malignancy. Superimposed on this process was a screening mechanism that allowed for the detection and removal of polyps and the detection and treatment of cancer. They placed hypothetical persons age 50 years, representative of the United States population, into health states defined by the presence or absence of a polyp or cancer (localized, regional, or digital) in either the distal or proximal colon. The population transitioned through the different health status stages on an annual basis (cycle length) based on probabilities estimated from the literature. The main outcome measures computed were (1) discounted lifetime costs, (2) life expectancy, and (3) the incremental CE ratios compared across the various screening strategies. In an initial analysis, compliance was assumed to be 60 percent with the initial screen and 80 percent with followup or surveillance COL. The most effective strategy for white men was found to be annual rehydrated fecal occult blood test (FOBT) plus sigmoidoscopy (SIG) every 5 years from age 50 to 85 years. This resulted in a 60 percent decrease in CRC incidence and an 80 percent decrease in CRC mortality compared with no screening and an incremental CE ratio of $92,900 per life-year gained compared with unrehydrated FOBT plus SIG every 5 years. In an analysis in which compliance with screening and followup was both assumed to be 100 percent, screening more often than every 10 years was found to be prohibitively expensive. Other recommended strategies were either less effective or cost more per life-year gained. Because of increased life expectancy among white women and greater CRC mortality among blacks, these CRC screening strategies were even more cost-effective than among white men. Researchers conclude that screening for CRC, even with less than perfect compliance, significantly reduces CRC mortality at costs comparable to other cancer screening procedures. Compliance rates significantly affect incremental CE ratios. 1 figure, 4 tables, 54 references.
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Guidelines for Colorectal Cancer Screening and Surveillance Source: Gastrointestinal Endoscopy. 51(6):777-782, June 2000. Summary: The American Society for Gastrointestinal Endoscopy presents its guidelines for colorectal cancer (CRC) screening and surveillance. There is mounting evidence
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about the efficacy of screening people at average risk for CRC. Studies of fecal occult blood testing (FOBT) have shown a 15 to 33 percent reduction in CRC-related mortality. Other studies show a reduction in CRC-related mortality between 59 to 80 percent in the portion of the colon examined (usually using rigid sigmoidoscopy). Estimates suggest that the overall reduction in CRC-related mortality from flexible sigmoidoscopy screening up to age 80 years could be up to 45 percent. Several groups have published new guidelines for CRC screening, including the American Cancer Society (ACS), United States Preventive Service Task Force, and a consortium of groups. All three groups suggest that people at average risk should begin yearly FOBT at age 50 years. People with a positive FOBT should have a colonoscopy or double contrast barium enema (DCBE) and flexible sigmoidoscopy. The three groups recommend the use of flexible sigmoidoscopy as part of a CRC screening program, though they differ in time intervals recommended. The ACS and the consortium endorse DCBE every 5 to 10 years for screening people at risk. Both the ACS and the consortium recommend colonoscopy every 10 years as an alternative for CRC screening, which has advantages such as complete visualization of the entire colon and therapeutic potential. Colonoscopy for cancer surveillance is appropriate in certain high-risk people. People with longstanding ulcerative colitis or Crohn's colitis may undergo colonoscopic surveillance with systematic biopsies every 1 to 3 years. People with a family history of familial adenomatous polyposis or Gardner's syndrome should undergo genetic testing with counseling and annual flexible sigmoidoscopy beginning at 10 to 12 years. Colectomy should be recommended when polyposis is found. Affected people have a nearly 100 percent chance of developing CRC by age 40 years. People with a family history of CRC or adenomas are also at increased risk for developing CRC. Colonoscopy is recommended every 3 to 5 years beginning at an age 10 years younger than the age of the youngest affected relative. People with a personal history of CRC are at increased risk for metachronous cancer and for the recurrence of the index cancer. They should undergo a preoperative colonoscopic exam if possible. Colonoscopy is the preferred method of postpolypectomy followup as it permits the removal of most recurrent polyps. Most polyps seen during colonoscopy can be completely removed by electrocautery, a safe procedure. 3 tables, 48 references. ·
Colorectal Cancer Screening by Detection of Altered Human DNA in Stool: Feasibility of a Multitarget Assay Panel Source: Gastroenterology. 119(5):1219-1227, November 2000. Summary: Researchers evaluated a multitarget fecal DNA assay panel as a possible screening technique for colorectal cancer (CRC). They assayed freezer-archived stool samples collected from 22 patients with CRC, 11 with adenomas 1 centimeter (cm) or smaller, and 28 patients with no colon abnormalities. The samples were collected from patients at the Mayo Clinic, Rochester, Minnesota, a few days before cathartic preparation for a scheduled colonoscopy (COL), which was used as the gold standard. Researchers isolated DNA from the samples by a sequence-specific hybrid capture technique. They analyzed the DNA for point mutations at any of 15 sites on the K-ras, p53, and APC genes, mutations associated with the Bat-26 gene (a microsatellite instability marker), and L-DNA (DNA that could be highly amplified by the polymerase chain reaction). They compared the results with the results of COL screening and the fecal occult blood test (FOBT). The FOBT had been performed only on the patients with adenomas and the patients with normal colons (controls). Analyzable DNA was recovered from all stool samples. The overall sensitivity of the assay versus COL was 91 percent for cancer and 82 percent for adenomas 1 cm or smaller. The specificity was 93 percent. If mutations in the K-ras gene were excluded from the panel and the results
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were compared with those of the FOBT, the sensitivity for cancer was unchanged, but was decreased slightly for adenomas, down to 73 percent. Specificity was increased to 100 percent. Researchers conclude that assay of altered DNA holds promise as a stool screening approach for detecting CRC. 3 figures, 4 tables, 49 references. ·
Colorectal Cancer Status and Trends Source: Kansas Health Statistics. (7):3-4, November 2000. Summary: The author discusses trends in the incidence of and mortality from colorectal cancer (CRC) in Kansas. About 74 percent of newly diagnosed CRC occur in people over age 64 years. Surviving CRC depends on how advanced it is at the time of diagnosis. In Kansas, the age-adjusted death rate for CRC, and the number of new cases, decreased between 1990 and 1998. Possible reasons for this include early detection, removal of localized CRC and precancerous growths, advances in treatment, and changes in risk prevalence. Routine screening using an endoscope or chemical examination of the stool for hidden blood is recommended for people over age 50 years, although the optimal frequency for these examinations has not been determined. Because of risk, cost, and discomfort, endoscopic examination of the colon is not widely practiced. In 1997, 69 percent of Kansans over age 49 years had not had a fecal occult blood test during the past 2 years, and 70 percent had not had proctosigmoidoscopy during the past 5 years. Although there is a need to develop more cost-effective, patient-acceptable ways of detecting colorectal cancer at its early stage, many premature deaths could be avoided by implementing current screening guidelines. 2 figures, 6 references.
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Dietary Fiber and the Risk of Colorectal Cancer and Adenoma in Women Source: New England Journal of Medicine. 340(3):169-176, January 21, 1999. Summary: Researchers examined associations between dietary fiber intake and the risk of colorectal cancer (CRC) and adenoma in women. They based the study on the Nurses' Health Study (NHS), a large cohort study of 121,700 female registered nurses in the United States. The NHS was initiated in 1976 to examine known and suspected risk factors for cancer and coronary heart disease when the nurses were between the age of 30 and 55. Researchers examined data on 88,757 NHS participants who completed a semiquantitative questionnaire on dietary intake of fiber, nutrients, and other foods in 1980, and who had no history of cancer, inflammatory bowel disease, or familial polyposis. The participants also completed dietary questionnaires in 1984 and 1986. The women were categorized according to quintiles with respect to fiber intake as computed from the 1980, 1984, and 1986 dietary questionnaires. They were followed up until May 31, 1996. During the 16-year followup period, 787 cases of CRC were diagnosed. Of 27,530 participants who underwent endoscopy, 1,012 were found to have adenomas of the distal colon and rectum. Within the entire cohort, the median energy-adjusted total dietary fiber intake differed by more than a factor of 2.5 between the highest and lowest quintiles. No association between dietary fiber intake and CRC risk was found by multivariate analysis after adjusting for age, established CRC risk factors, and total energy intake, the relative risk (RR) being 0.95. This lack of a protective effect was still observed when total energy intake, events during the first 6 years of followup, and women who altered their fiber intake during the followup period were excluded from analysis. When specific fiber types wer e considered, only fruit fiber was associated with any decrease in risk, the RR being 0.86; however, the decrease was not statistically significant. Increased consumption of vegetable fiber was actually associated with a significant increase in CRC risk, RR 1.35. No association between fiber intake and the ris k of colorectal adenoma was found. Researchers concluded that these results do not
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support the existence of an important protective effect of dietary fiber against CRC or adenoma. 6 tables, 37 references. ·
Food Groups and Colorectal Cancer Risk Source: British Journal of Cancer. 79(7-8):1283-1287, March 1999. Summary: Researchers investigated the relationship between food group intake patterns and the incidence of colorectal cancer, using data from a case/control study conducted in the Swiss canton of Vaud, an area with intermediate colorectal cancer rates. The study ran from January 1992 through June 1997. Cases were patients with incident histologically confirmed colon or rectal cancers who had been admitted to a particular hospital. The case series included 223 patients, 142 of whom were men, with colon (199) or rectal (104) cancers. Their median age was 63 years. Control participants included 491 patients, 211 of whom were men, admitted to the same hospital for acute nonneoplastic conditions unrelated to long-term modification of diet. Interviewers administered a food-frequency questionnaire to assess habitual diet, including average weekly frequency of consumption of specific foods or food groups. The findings confirmed that food intake patterns have a role in the risk of colorectal cancer, even after allowance for total energy, and a number of major nondietary correlates. Results indicated that there is a direct association between colorectal cancer risk and meats, specifically red meat, and an inverse one between cancer risk and various types of vegetables and fruit. Coffee drinking was protective, and alcohol was associated with a moderately increased risk. This protection is shared by a wide spectrum of fruits and vegetables, and is probably due to substances that are thermoresistant. Of special interest is an inverse relation with garlic, which has been related to reduced risk of gastric cancer in other studies. This has been linked to selected constituents of garlic, such as allyil sulfides, to an antibacterial or a more specific chemopreventive role of garlic. Whole grain, but not refined grain, was inversely related to colorectal cancer risk. 4 tables, 30 references.
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Psychological and Behavioral Factors Associated with Colorectal Cancer Screening Among Ashkenazim Source: Preventive Medicine. 29(2):119-125, August 1999. Summary: Researchers examined psychological and behavioral factors related to annual colorectal cancer (CRC) screening in a sample of Ashkenazi Jewish individuals. Participants were recruited through radio, television, and newspaper notices as well as through local Jewish publications, newsletters of Jewish organizations, synagogues, the Jewish Community Center, and Baylor College of Medicine in Houston, Texas. Eligible participants were 171 Ashkenazi Jewish adults, over age 39, attending an educational program about breast cancer genetics and the 185delAG mutation among Ashkenazi Jews. The participants completed questionnaires immediately after the educational session and before completing DNA testing. Researchers also gathered data 1 and 6 months following receipt of DNA test results. Variables measured included selfreported personal and family histories of cancer and CRC, demographics, and various medical and psychological variables. To assess compliance with CRC screening behaviors, participants were asked whether they had had digital rectal examination and/or fecal occult blood testing during the previous 12 months. Certain components of the Health Belief Model were addressed by asking about perceived risk of colon cancer, cues to action, and cancer worry. Data analysis indicated that overall, compliance with recommended CRC screening was low, even among high-risk individuals. Digital rectal examinations and fecal occult blood tests had been obtained in the past year by 46 percent and 31 percent of participants, respectively. Physician recommendation
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significantly related to obtaining a digital rectal examination. Physician recommendation and education significantly related to obtaining fecal occult blood tests. Although participants with a family history of CRC perceived themselves as being at increased risk of developing CRC, and were more worried about developing colon cancer, they were no more likely to adhere to CRC screening guidelines than were those without such histories. The researchers conclude that physicians need to encourage all asymptomatic patients age 50 and older to be screened for CRC. 4 tables, 39 references. ·
Colorectal Cancer Screening: An Overview of Available Methods and Current Recommendations Source: Southern Medical Journal. 92(3):258-265, March 1999. Summary: Researchers used the MEDLINE database to identify articles addressing the rationale for colorectal cancer screening, methods used, effectiveness of the methods, and current recommendations. Colorectal cancer is a common malignancy in the United States that is curable when detected early and is potentially preventable. Screening for colorectal cancer is one way to change the incidence and outcome. Methods of screening include flexible sigmoidoscopy, fecal occult blood tests, combined flexible sigmoidoscopy and fecal occult blood tests, air-contrast barium enemas, and colonoscopy. Guidelines exist for screening people at average risk for colorectal cancer. The American Cancer Society now endorses screening with flexible sigmoidoscopy every 5 years and fecal occult blood tests yearly, beginning at age 50, or a total colon examination (barium enema or colonoscopy) every 5 to 10 years. A cost-effectiveness analysis of colon cancer screening shows that the cost-effectiveness of such screening tests is dramatically affected by compliance. Screening recommendations for people at high risk are based on the risk factor and determined by both clinical trial data and expert opinion. This includes personal history of adenomatous polyps or colorectal cancer, family history of colorectal cancer, polyposis syndromes, hereditary nonpolyposis colon cancer syndromes, and inflammatory bowel syndrome. No tools currently exist for identifying people with genetic mutations associated with development of adenomatous polyps or cancer. New molecular techniques may allow detection of genetic mutations that signify an increased risk and identify individuals most likely to benefit from screening. 1 figure, 4 tables, 34 references.
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Screening for Colorectal Cancer and Other GI Cancers Source: Current Opinion in Oncology. 11(4):305-311, July 1999. Summary: Currently, screening is recommended for the prevention of colorectal cancer in average and high-risk populations. For average risk populations, large randomized trials support the use of screening fecal occult blood testing, and case-control studies support the use of screening sigmoidoscopy. To date, there are very limited data addressing whether the combination of annual fecal occult blood testing and flexible sigmoidoscopy every 5 years would offer greater reductions in colorectal mortality than would either test alone. This year, several investigators have addressed issues related to the probability of identifying advanced lesions in the proximal colon following a positive screening flexible sigmoidoscopy. Similarly, two studies identified that villous histology in an index polyp was associated with an increased risk for recurrent colonic polyps. Additionally, two large trials provided new insight about the prevalence of mutations in the MLH1 or MSH2 mismatch-repair genes among people with colorectal cancer. Lastly, a case-control study from Sweden provided the best evidence to date that surveillance colonoscopies for people with long-standing ulcerative colitis may reduce cancer-related mortality. There is strong evidence for the effectiveness of screening for
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colorectal cancer in average risk populations. Further efforts are needed to increase compliance with current screening guidelines. For people at high risk, the effectiveness of screening programs to reduce mortality is less well-established. Although further work is needed, these studies have served to advance knowledge of colorectal cancer screening substantially. 2 tables, 41 references. ·
NCCN Colorectal Cancer Screening Practice Guidelines Source: Oncology. 13(5A):152-179, May 1999. Summary: Researchers present colorectal cancer screening guidelines, focusing on people with normal risk and those with inflammatory bowel disease, and individuals with high risk who are genetically predisposed to develop colon cancer. Section 1, Normal-Risk Individuals, discusses screening for colon cancer, which includes fecal occult blood testing, flexible sigmoidoscopy, colonoscopy, and double-contrast barium enema. Section 2, Inflammatory Bowel Disease, discusses the fact that people with 8 or more years of pancolitis or 15 or more years of left-sided colitis are at increased risk for colorectal cancer. Surveillance techniques, in the form of colonoscopic biopsies, are available for these people. Surveillance should be performed by someone familiar with the appearance of chronic inflammatory bowel disease. Section 3, Familial Adenomatous Polyposis (FAP), points out clinical features of FAP, an autosomal dominant condition primarily affecting the gastrointestinal tract that is associated with a nearly 100-percent cumulative lifetime risk of colorectal cancer. There is a distinction between people with a personal history of FAP and those who are presymptomatic but considered at high risk based on a family history of FAP. It is important to provide them with genetic counseling so they are able to make informed decisions about the implications of genetic testing and the implications for their own management. Not all families with FAP carry known mutations of the adenomatous polyposis coli (APC) gene. Section 4, Hereditary Nonpolyposis Colorectal Cancer (HNPCC), discusses an area where the data supporting screening guidelines are much less readily available. It notes information that must be collected when taking a family history and discusses molecular workup for the HNPCC and molecular workup for microsatellite instability (MSI/RER) positive tumors. A series of 23 figures provide the information for these guidelines. 23 figures, 1 table, 5 references.
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Flexible Sigmoidoscopy: Screening for Colorectal Cancer Source: American Family Physician. 59(6):1537-1546, March 15, 1999. Summary: Flexible sigmoidoscopy is an important screening procedure because of its ability to detect early changes in the distal colon. It is a valuable procedural skill for family physicians. Colorectal cancer screening is performed with a rigid 25-cm scope or flexible 35-cm or 60-cm scopes. The 60-cm flexible sigmoidoscope provides excellent visualization with minimal discomfort to patients. Complications from the procedure can include abdominal cramping, bloating, discomfort, postprocedure bleeding, and bowel perforation. Patient preparation includes a complete medical history and cleansing of the bowel using two enemas on the morning of the examination or adding an oral cathartic. Antibiotic prophylaxis for bacterial endocarditis associated with the procedure is optional. The author explains equipment necessary for conducting flexible sigmoidoscopy and describes the procedure, focusing on insufflation, suction, rinse, biopsy, hook and pullback, dithering-twist maneuver, jiggling, and retroflexion j maneuver. Discussion of abnormal findings noted that patients with the following pathologic conditions should be referred for colonoscopy: (1) Hemorrhoids, (2) anal fissures, (3) rectal cancers, (4) diverticula, (5) Crohn's colitis, (6) ulcerative colitis, (7)
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pseudomembranous colitis, and (8) adenocarcinoma. Recommendations for reducing the risk of colon cancer include (1) participating in daily physical activity; (2) maintaining a low-fat, high-fiber diet; (3) stopping smoking; and (4) limiting alcohol consumption. 12 figures, 1 table, 21 references. ·
Colon Polyp Registries and Colorectal Cancer Control Source: Cancer Detection and Prevention. 23(6):474-478, 1999. Summary: A cohort of 252 subjects in the Roger Williams Hospital Polyp Registry who had adenomatous polyps removed in 1990 was followed for 6 years. Thirty subjects died during this period. Followup rate for the 222 living patients was 85 percent. New adenomatous polyps were found in 59 percent of the endoscoped subjects. Risk factors for new polyps included (1) family history of colorectal carcinoma, (2) right-sided location, and (3) prior adenomatous polyps. In addition, three colorectal carcinomas, two of which were Dukes stage A, were found 1, 1, and 6 years after the index polypectomy. If, as is common practice, the two first-year cancers are excluded, the observed incidence of metachronous colorectal cancer was 0.8/1,000 patient-years, which is substantially less than the expected incidence of such carcinomas in reference populations. Compared to the 1984 and 1987 cohorts in the polyp registry, colonoscopy was used more frequently and sigmoidoscopy less so for surveillance. Within the sigmoidoscopy group, the flexible instrument continued to rise in popularity as compared with rigid sigmoidoscopy. In addition to helping reduce the incidence of metachronous colorectal carcinoma, the polyp registry also serves the educational function of sensitizing physicians and their patients to the need to detect and treat these premalignant lesions. Enrollees in the registry also provide a source of studies designed to elevate possible inhibitory effects of dietary, chemopreventive, and other agents on colorectal neoplasias. 4 tables, 10 references.
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How Does Colorectal Cancer Present? Symptoms, Duration, and Clues to Location Source: American Journal of Gastroenterology. 94(10):3039-3045, October 1999. Summary: Researchers examined possible associations between gastrointestinal symptom characteristics and colorectal cancer (CRC). They reviewed hospital and clinical records of primary care physicians and specialists for 204 consecutive patients with CRC who were first diagnosed at North Carolina Memorial Hospital between May 1983 and June 1987. Data on demographic characteristics, presence and duration of 15 symptoms and symptoms and characteristics of the tumor, including location and stage, were abstracted from the records. Signs and symptoms included (1) a positive fecal occult blood test (FOBT), (2) rectal bleeding, (3) anemia, (4) abdominal pain, (5) weight loss, (6) anorexia, (7) constipation, (8) altered stools, (9) fatigue, (10) diarrhea, (11) nausea or vomiting, (12) tenesmus, (13) mucus in stools, (14) rectal pain, and (15) obstruction. Researchers used factor analysis and multivariate logistic regression analysis techniques to examine associations between location and stage of the tumor, and symptom characteristics. The patient group was elderly, mean age 66, as likely to be male as female, and predominantly white. Eighty-three percent of the cases of CRC were detected because of an investigation of related symptoms. The remaining 17 percent were detected by accident. Twenty-five percent of the patients had metastatic cancer at the time of diagnosis. The majority (58 percent) of the tumors were located in the distal colon and classified as Duke's stage A and B (55 percent). The most common symptoms were rectal bleeding, abdominal pain, and change in bowel habits, being reported 58, 52, and 57 percent, respectively. Fifty-seven percent of the patients had anemia and 77 percent had occult bleeding, detected by the FOBT. The median duration of symptoms
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(from onset to diagnosis) was 14 weeks. No association was found between overall duration of symptoms and stage of the tumor. Patient, gender, and proximal location of the tumor were also not associated with a longer duration of symptoms before diagnosis. Independent predictors of a distal location of CRC found by multiple logistic regression analysis were (1) anemia, (2) rectal bleeding, (3) constipation, (4) and proximal symptoms (at least one of anorexia, nausea, vomiting, abdominal pain, or fatigue). These predictors, when incorporated into a decision rule, had a sensitivity of 93 percent and a sensitivity of 47 percent. Researchers concluded that CRC presents with many common symptoms of long duration. The results indicated no association between duration of symptoms before diagnosis and cancer stage, a marker of prognosis. Some symptoms, however, were found to be associated with cancer location and presentation might assist in diagnostic evaluation. Until prevention of CRC is more common, clinical findings must be relied on for detecting CRC. The results of this study will remind physicians to keep CRC on the differential diagnosis of chronic gastrointestinal symptoms, and the decision rule may prompt earlier investigations with colonoscopy. 3 figures, 4 tables, 34 references. ·
Colorectal Cancer Screening: Making Sense of the Different Guidelines Source: Cleveland Clinic Journal of Medicine. 66(5):303-311, May 1999. Summary: The authors review the colorectal cancer screening guidelines from the American Cancer Society (ACS), the United States Preventive Service Task Force, and a consortium including the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, the American College of Gastroenterology, the American Society of Colon and Rectal Surgeons, and the Society of American Gastrointestinal Endoscopic Surgeons. The guidelines differentiate between persons at average risk and those with risk factors such as (1) personal or family history of colonic adenomas or colorectal cancer, (2) constitutional genetic mutations, and (3) chronic inflammatory bowel disease. Screening in persons at average risk should begin at age 50. Four methods of screening are (1) fecal occult blood testing (FOBT), (2) flexible sigmoidoscopy, (3) barium enema radiographic examination with flexible sigmoidoscopy, and (4) colonoscopy. All three screening guidelines recommend FOBT every year. The ACS and the consortium recommend performing flexible sigmoidoscopy every 5 years in persons at average risk. The United States Preventive Service Task Force recommends flexible sigmoidoscopy, but does not specify how often. Colonoscopy should be performed if the other screening examinations show abnormalities. Most people at moderate risk of colon cancer need to undergo colonoscopy at regular intervals. The authors recommend that persons with adenomas or with previous colorectal cancer undergo colonoscopy 3 years after surgery and, if negative, every 5 years thereafter. Persons at high risk for colon cancer are (1) those with genetic syndromes, such as familial adenomatous polyposis; (2) Ashkenazi Jews; and (3) those with inflammatory bowel disease. The authors recommend genetic testing for those with genetic syndromes and for Ashkenazi Jews with a personal or family history of colon cancer. The authors conclude that screening and surveillance for colorectal adenomas and cancer should be continued as long as the patient is expected to benefit from it. 1 figure, 4 tables, 45 references.
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Screening and Surveillance for Colorectal Cancer Source: Seminars in Oncology. 26(5):485-498, October 1999. Summary: The authors review (1) the current literature on colorectal cancer screening tests in average- and high-risk populations, (2) recommended guidelines for screening
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and surveillance, and (3) the cost-effectiveness of colorectal cancer screening and surveillance. Average-risk patients are asymptomatic persons over age 50 with no personal or family history of colorectal cancer or adenomatous polyps and no history of inflammatory bowel disease. Three prospective, randomized, controlled trials from Minnesota, Denmark, and the United Kingdom have shown the effectiveness of fecal occult blood testing (FOBT) in reducing colorectal cancer mortality rates. Two retrospective case-control studies from California and Germany have provided more evidence to support the effectiveness of FOBT. A retrospective case-control study from California has shown that sigmoidoscopy can significantly reduce rectosigmoid cancer mortality. Substantial indirect evidence suggests that colonoscopy is an effective screening test for average-risk patients. Double-contrast barium enema may be considered an alternative for examination of the large bowel in average-risk patients. High-risk patients (1) are age 50 and older, (2) consume a high-fat/low-fiber diet, (3) consume an excess of calories, (4) have a personal or family history of colorectal cancer, (5) have a history of inflammatory disease, or (6) have a genetic predisposition due to hereditary polyposis or nonpolyposis syndrome. All average-risk persons should begin colorectal cancer screening at age 50 with an annual FOBT and a flexible sigmoidoscopy every 5 years. Colonoscopy should be performed after a positive FOBT. Another screening approach for average-risk persons is colonoscopy every 10 years. Colonoscopy is the preferred surveillance test for high-risk patients. A report prepared by the Office of Technology Assessment of the United States Congress concluded that colorectal cancer screening is cost-effective. 2 figures, 3 tables, 102 references. ·
Costs and Cost-effectiveness of Colorectal Cancer Prevention and Therapy Source: Seminars in Oncology. 26(5):561-568, October 1999. Summary: The authors discuss the costs and cost-effectiveness of colorectal cancer prevention and therapy. There are two main categories of health economic analyses: (1) Attributable cost studies, and (2) comparative cost studies. Attributable cost studies quantify the amount of money required to prevent or treat a condition. Comparative cost studies relate money spent to health benefit gained and evaluate the differences between alternative health intervention strategies. No published reports have examined the attributable costs of primary colorectal cancer prevention. Several studies have reported the attributable costs of treating colorectal cancer, specific to stage at diagnosis and phase of therapy. An examination of Medicare claims data showed that (1) initial care for colorectal cancer cost $17,505, which was 41 percent of the total; and (2) terminal care cost $12,028, which was 28 percent of the total. The average payment from diagnosis to death for patients surviving more than 1 year was $51,865. Two health maintenance organization studies found slightly higher attributable costs of colorectal cancer. Use of different methodologies limits direct comparability of published attributable cost of colorectal cancer studies. The consensus among comparative health economic analyses of colorectal cancer is that population colorectal cancer screening for average-risk persons is cost-effective, but not cost-saving, when compared to no intervention. Colorectal cancer surveillance strategies among high-risk persons with polyps, inflammatory bowel disease, or genetic predispositions for colorectal cancer appear to be cost effective when compared with no surveillance. Genetic testing for mutations in any of the hereditary nonpolyposis colon cancer genes appears to be cost effective. The authors conclude that challenges remain in assessing the economic implications of various approaches to the prevention and treatment of colorectal cancer. 1 table, 33 references.
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Dietary Factors and Genetic Susceptibilities in Colorectal Cancer Risk: A Brief Review Source: Clinical Nutrition. 14(4):31-38, September 1999. Summary: The author presents an overview of dietetic factors and genetic susceptibility involved in colorectal cancer (CRC) risk. The review considers the following topics: (1) Incidence of and mortality from CRC, (2) CRC risk factors, (3) estimates of CRC cases preventable by dietary means, (4) diet assessment in CRC epidemiology, (5) studies investigating dietary factors associated with CRC risk, (6) the process of colon carcinogenesis, (7) genes that affect colon cancer risk, (8) the role of gatekeeper versus caretaker gene mutations in cancer risk, (9) the role of gene-diet interactions in CRC, and (10) dietary recommendations for preventing CRC. Since incidence rates for CRC vary 20-fold internationally, environmental factors such as diet may account for some of this variability. Established risk factors for CRC include (1) family history of CRC, (2) germline or somatic mutations in specific genes, and (3) history of inflammatory bowel disease. Less well established are hypotheses that certain dietary factors may increase or decrease CRC risk. These include (1) dietary calcium, (2) dietary fat, (3) putative carcinogens in cooked meat products, (4) low vegetable intake, and (5) possibly low fiber and folate intake. Quantifying the interactions between specific dietary factors on CRC risk in persons with known genetic risk factors has become a major focus of research. Two recent studies investigating dietary factors associated with CRC have suggested that dietary fiber may not protect against CRC, and that dietary calcium may have a positive effect on intermediate biomarkers of CRC risk. It is thought that dietary factors may exert protective effects at multiple points in genetically controlled pathophysiologic pathways that lead to CRC. Experimental data indicate that a specific mutation in the gene coding for the folate methylating enzyme methylene tetahydrofolate reductase may interact with low dietary folate intake and/or high alcohol intake to modify CRC risk. This and other genotype-specific interactions with dietary factors represent one of the most exciting areas of development in the field of nutritional epidemiology. Consumption of a plant food-based diet with limited intakes of animal products and alcohol is a consensus recommendation to reduce CRC risk. 3 figures, 1 table, 14 references.
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Colorectal Cancer Screening Source: Primary Care. 26(1):179-187, March 1999. Summary: A physician discusses colorectal cancer (CRC) screening, including (1) the epidemiological aspects of CRC, (2) screening techniques for CRC, (3) the types of colorectal polyps, (4) stratification of patients according to their risk of CRC, and (5) recommendations for CRC screening made by organizations such as the American Cancer Society. Screening techniques discussed include (1) digital rectal examination, (2) fecal occult blood test (FOBT), (3) flexible sigmoidoscopy, (4) colonoscopy, and (5) double contrast barium enema. The discussion of screening techniques considers the advantages and disadvantages of each procedure and their applicability to patients judged to be at average, moderate, and high risk for CRC. General CRC screening recommendations are that an annual FOBT and flexible sigmoidoscopy every 5 years are recommended for persons at average risk. Colonoscopy is considered the gold standard for visualizing the entire colon and is reserved for abnormal findings on FOBT or flexible sigmoidoscopy, or for persons at greater than average risk for CRC. 14 references.
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Screening for Colorectal Cancer: What's the Best Strategy? Source: IM Internal Medicine. 20(3):12-21, March 1999. Summary: In this discussion on screening approaches for colorectal cancer (CRC), the author (1) reviews the pathophysiology and presentation of CRC; (2) discusses the strengths and weaknesses of the available tests; and (3) discusses stratification of patients into average, moderate, and high CRC risk categories for screening. Screening tests discussed include (1) fecal occult blood test (FOBT), (2) flexible sigmoidoscopy (SIG), (3) double contrast barium enema, (4) digital rectal examination, and (5) colonoscopy (COL). The cost-effectiveness of the screening tests is also considered. The author presents a practical approach for screening patients based on their risk. Persons with hereditary nonpolyposis colon cancer, familial adenomatous polyposis, or inflammatory bowel disease are considered at high risk for CRC and should be monitored with surveillance COL. Persons with the following attributes are considered to be at moderate risk for CRC: (1) Personal history of adenomatous polyps; (2) personal history of CRC or breast, ovarian, or endometrial cancer; and (3) persons with a family history of adenomas or CRC (especially first-degree relatives with age of onset under 60). The first two groups should be monitored with surveillance COL. The third group should have annual screening beginning at age 40 (either surveillance COL or annual FOBT with SIG every 3 to 5 years based on degree of risk). Persons over age 50 years with no other risk factors are considered at average risk. They should have FOBT annually and SIG every 3 to 5 years. 1 figure, 4 tables, 37 references.
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Screening Endoscopy and Risk of Colorectal Cancer in United States Men Source: Cancer Causes and Control. 9(4):455-462, August 1998. Summary: Researchers evaluated the efficacy of screening endoscopy (sigmoidoscopy (SIG) or colonoscopy (COL)) for colorectal cancer (CRC) in United States men. They utilized data from a prospective study of 51,529 United States male health professionals. The study participants (dentists, optometrists, podiatrists, osteopaths, pharmacists, and veterinarians), age 40 to 75, were followed from 1986 to 1996 using a postal questionnaire that was sent out at 2-year intervals. The questionnaires sought information on exposures and new cases of major illnesses, including CRC. In 1990, 1992, and 1994, the participants were asked if they had been screened by SIG or COL durin g the preceding 2 years. Information on any cancer diagnoses and death was also requested in the biennial questionnaires. The National Death Index was also searched to identify deaths among nonrespondents. Incidence rates for CRC by stage (Dukes A and B, or Dukes C and D) and site (proximal or distal) were calculated first based on screening status in 1986, and then with screening status updated, based on responses to subsequent questionnaires. CRC rate ratios (RR's) were computed from the incidence and mortality rates for screened participants, which were compared to the incidence and mortality rates for unscreened participants. Being screened by SIG or COL in 1986 and 1987 was significantly associated with a decreased risk of all CRC, cancer in the distal colon or rectum, Dukes stage A and B CRC, Dukes stage C and D CRC, and mortalit y from CRC, RR's being 0.58, 0.40, 0.66, 0.50, and 0.56, respectively, as determined by mulivariate logistic regression after controlling for (1) age, (2 ) physical activity, (3) dietary consumption of fat and saturated fat, (4) family history of colon cancer, and (5) other known CRC risk factors. Screening endoscopy in 1987 and 1988 appeared to provide strong protection against distal stage C and D CRC, the age-adjusted RR being 0.16. Screening endoscopy appeare d not to provide protection against proximal stage C and D cancers, the RR being 0.96. Researchers concluded that these findings provide strong evidence that screening endoscopy protects against CRC incidence and mortality.
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Most of the endoscopies were SIG, and it is probable that most of the SIG procedures used a flexible sigmoidoscope. This would be consistent with the statistically significant decrease in the incidence of distal CRC, which would be within reach of a flexible sigmoidoscope, while there was no decrease in the incidence of proximal CRC. 2 tables, 35 references. ·
Colorectal Cancer in Women: An Underappreciated But Preventable Risk Source: Journal of Women's Health. 7(1):45-48, February, 1998. Summary: The authors present a review of the colorectal cancer (CRC) risk in women, including (1) the epidemiological aspects of colon cancer in women, (2) the biological characteristics of CRC and their implications for screening, (3) screening techniques for CRC, (4) recommendations for CRC screening, and (5) barriers to CRC screening in women. CRC accounts for more than 65,000 new cases and 24,000 deaths in women each year. CRC is the third most common type of tumor in women, following breast and lung cancer. For women who are currently age 65, the risk of death from CRC over the next 20 years is about equal to the risk of death from breast cancer. The high incidence of, and mortality from, CRC in women is underappreciated by the general public. This serious level of misperception is indicated by the large number of articles about breast cancer in the lay press, compared with those about CRC. The authors note that mortality from CRC does appear to be decreasing, possibly because of lifestyle changes and earlier detection by screening tests. CRC mortality can be reduced even further by the effective use of currently-available screening and surveillance modalities. Screening and surveillance for CRC are facilitated by two key factors related to the biology of the disease: (1) CRC is highly curable when diagnosed at an early stage, and (2) because the majority of colon cancers arise in previously benign colonic polyps, there is a substantial period of time (up to several years) in which removal of the polyps can reduce the risk of malignancy. The United States Preventive Task Force recently recommended universal screening for CRC after age 50. Strong evidence from randomized controlled trials and case-control studies supports the use of testing for occult blood in stool and flexible sigmoidoscopy every 5 to 7 years. Although the risk of CRC is similar in men and women, women frequently have the misconception that CRC is a man's disease. At least partially because of this, women are less likely than men to undergo screening sigmoidoscopy. Other barriers to screening include (1) primary care providers' lack of awareness of updated guidelines, (2) patients' lack of compliance with multiple screening tests, and (3) patients' fear of discomfort. Calculations made by the authors indicate that the risk of CRC in women can be reduced by 67 percent (versus 40 percent for breast cancer and 90 percent for cervical cancer) in those who undergo screening and subsequent surveillance to remove further polyps. Because of this, it is considered critical that women be specifically targeted to undergo screening tests for CRC. 1 figure, 26 references.
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Colonoscopy in the Screening and Surveillance of Individuals at Increased Risk for Colorectal Cancer Source: Gastrointestinal Endoscopy. 48(6):676-678, December 1998. Summary: A series of guidelines outline the appropriate use of colonoscopy in the surveillance of individuals at increased risk of colorectal cancer. Section 1, Purpose of this Document, introduces the issue. Section 2, Patients with Significant Personal History, explains the increased risk of colorectal cancer for individuals who have a personal history of colon cancer, individuals who have a personal history of colorectal neoplastic polyps, and individuals who have a personal history of inflammatory bowel
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disease. Section 3, Patients with Significant Family History, explains that individuals with a significant family history of colorectal neoplasia are at increased risk for colorectal cancer. Recognized syndromes include familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer syndrome, and familial risk of sporadic colorectal cancer. A summary of recommendations for screening and surveillance colonoscopy in individuals at increased risk for colorectal cancer focusing on individuals with a significant personal history and individuals with a significant family history is provided. 11 references. ·
What to Do Now to Screen for Colorectal Cancer Source: Patient Care. 32(11):206-220, June 15, 1998. Summary: The author reviewed current guidelines for colorectal cancer screening. Colorectal cancer is an excellent target for systematic screening because (1) it is the second greatest cause of death from cancer in the United States, (2) it affects men and women equally, and (3) early-stage colorectal cancer is most often curable with surgical resection. Despite this evidence, colorectal cancer screening rates in the United States are low. The American Cancer Society (ACS) recommends that screening for persons at average risk begin at age 50 with one of the following: (1) Fecal occult blood test (FOBT) every year combined with flexible sigmoidoscopy or total colon examination, then FOBT every year and flexible sigmoidoscopy every 5 years; (2) colonoscopy every 10 years; or (3) double-contrast barium enema every 5 to 10 years. The ACS recommends that screening begin at least by age 40 for people who have a family history of colorectal cancer or adenomatous polyps, or 10 years before the age at which the youngest family member was affected. The author provided the ACS guidelines for colorectal cancer screening and a flowchart for determining when to screen. The author concluded that (1) primary care physicians can help educate the public about the risk of colorectal cancer among people age 50 and older, and (2) Medicare reimbursement for any of the four recommended screening tests removes a major barrier to more widespread screening. 3 figures, 1 table, 12 references.
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Proven Value of Screening Sigmoidoscopy for Colorectal Cancer Source: JAAPA: Official Journal of the American Academy of Physician Assistants. 11(2):30-32, 35-38, 40, February 1998. Summary: The author reviews screening strategies and procedural methods that promote early detection and prevention of colorectal cancer (CRC) in the asymptomatic patient, with emphasis on screening sigmoidoscopy. Although flexible sigmoidoscopy (FS) has been shown to provide a significant reduction in mortality from CRC, only a small proportion of patients receive appropriate, timely FS screening. FS permits direct visualization of the anus, rectum, and distal colon. It can detect polyps, cancer, and other disorders, such as inflammatory bowel disease and diverticulosis. The American Cancer Society's guidelines for CRC screening recommend that beginning at age 50, asymptomatic, average-risk patients should undergo fecal occult blood testing annually, and FS and digital rectal examination every 5 years. A possible role for physician assistants (PA's) in FS is discussed. PA sigmoidoscopists can provide an economical and reliable alternative to current practices without sacrificing the patient's comfort or the reliability of the test. All PA's who are interested in performing this procedure should enroll in a sigmoidoscopy training program and adhere to a standardized protocol. The American Society for Gastrointestinal Endoscopy recommends that an endoscopist trainee perform 20 to 30 procedures to become competent in performing a sigmoidoscopy. 3 figures, 22 references.
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Colorectal Cancer Prevention: Clinical Implementation in a Primary Care Clinic Source: Medical Journal of Allina. 7(3), 6 p., Summer 1998. Contact: INTERNET/EMAIL: http://www.allina.com/Allina_Journal/Summer98/allen.html. Summary: Researchers developed a primary care-based colorectal cancer (CRC) prevention program that was piloted at the Litchfield Medical Clinic, Litchfield, Minnesota. The program was intended to maximize clinical effectiveness while minimizing clinic resources. It includes (1) risk assessment of all patients in the appropriate age categories, (2) primary prevention, (3) professional and patient education, (4) easy access to specialists, and (5) an ability to track clinical outcomes. The program is based on a visit planning model in which a health professional is assigned to ensure that clinic patients are current with recommended preventive health measures, reviewing patients' charts when they are scheduled for upcoming visits and identifying preventive health measures in need of updating. The health professional places a risk assessment tool, the Colon Cancer Risk Quiz, on the front of the chart of any patient age 40 to 80 years. The quiz facilitates the collection of data needed to stratify patients into average, increased, or high-risk categories. People who have a family history of cancer also complete a family cancer history form. The rooming nurse reviews the completed forms with the patients and stratifies them into one of the three CRC risk categories. During the clinic visit, the physician reviews the information, offers brief CRC education with written material, and makes screening recommendations based on national guidelines. People over age 49 years who are at average risk receive three screening choices, each of which provides acceptable risk reduction, although the three vary by frequency of exam and initial cost. People at increased and high risk are referred for colonoscopy at recommended ages and intervals, with no additional screening exams. People who complete the Quiz receive written information about primary prevention and screening tests tailored to their risk category. A database was developed to track the data. Initial results from 215 patients show that most fell into the average-risk category and were advised to complete fecal occult blood testing and sigmoidoscopy. About 80 percent of the patients understood and agreed to screening recommendations they received from their physicians. Preliminary analysis of the impact of visit planning shows a significant increase in the delivery of preventive health measures when previsit chart review was used. 3 figures, 2 tables, 12 references.
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Relative Sensitivity of Colonoscopy and Barium Enema for Detection of Colorectal Cancer in Clinical Practice Source: Gastroenterology. 112(1):17-23, January 1997. Summary: Researchers examined the relative sensitivity of colonoscopy and barium enema for detection of colorectal cancer in a broad range of clinical practice environments and in a broad geographic region. The researchers (1) invited 24 hospitals of various sizes in communities of various sizes across central Indiana to participate, (2) collected data from 20 hospitals, (3) reviewed the hospitals' consecutive cancer cases from 1988 to 1993, (4) collected patient information and data pertaining to screening from medical records, and (5) classified each case based on type of screening test. Results showed that (1) 2,193 patients with colorectal cancer were identified; (2) the mean age was 69.8 years, and 52 percent were women; (3) 535 patients were excluded because initial diagnosis was made by some other procedure; and (4) among the remaining 1,658 patients, 719 were defined as primary barium enema, and 941 as primary colonoscopy. Other results showed that (1) of the barium enema cases, barium
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enema detected cancer in 596 and missed the cancer in 123 for a sensitivity of 82.9 percent; (2) of the primary colonoscopy cases, colonoscopy detected cancer in 894 and missed the cancer in 47 for a sensitivity of 95.0 percent; (3) the odds ratio of a miss by barium enema compared with a miss by colonoscopy was 3.93; (4) the sensitivity of colonoscopy was lowest for splenic flexure cancers at 88 percent and cecal cancers at 90 percent; and (5) barium enema sensitivity was above 90 percent only in the descending colon and was lowest in the rectum (77 percent) and the cecum (75 percent). The researchers recommended that (1) hospitals institute review of barium enema and colonoscopy sensitivity for colorectal cancer detection by radiologists and colonoscopists; (2) in hospitals where the sensitivity of colonoscopy exceeds that of barium enema, barium enema should be abandoned; and (3) neither colonoscopy nor barium enema are foolproof methods for colorectal cancer detection. 5 tables, 42 references. ·
Colorectal Cancer: The Role of Screening and Surveillance Source: Journal of Investigative Medicine. 44(5):216-227, June 1996. Summary: Screening and surveillance programs for colorectal cancer are supposed to detect adenomas and carcinomas at an early state in order to reduce the incidence of colorectal cancer and decrease the associated morbidity and mortality. However, to implement these programs successfully will require a high compliance rate of both physicians and patients, and a change in current reimbursement policies to insure Medicare coverage. The most common type of colorectal cancer is sporadic, where no risk factors for colon cancer can be identified. The hereditary types of colorectal cancers are divided into two major groups: (1) Hereditary nonpolyposis colon cancer and the polyposis syndromes; and (2) familial adenomatous polyposis, and Gardner's and Turcot's syndromes. Adenomatous polyps are neoplastic lesions of the epithelial cells of the colon that lead to abnormal cellular proliferation and differentiation. As an adenoma grows, it attains more villous characteristics and an increasing degree of dysplasia. The biochemical changes that result in uncontrolled cellular proliferation of colonic epithelial cells have long remained a puzzle. However, a remarkable advanced knowledge of genetic and biochemical alterations in neoplasia over the past decade has occurred. The development of colon carcinoma in an adenomatous polyp appears to be the result of several genetic alterations that accumulate during progression from adenoma to carcinoma. Ther e is a substantial variation in the prevalence rate of colonic adenomas in different parts of the world. The currently recognized risk factors in adenoma development are hereditary factors, age, and diet. Fecal occult blood testing should begin at age 40 and be repeated annually. Flexible sigmoidoscopy should be performed at age 50, and after two negative tests 1 year apart, the test should be repeated every third year. A family history of one or more first-degree relatives with colon cancer places an asymptomatic person in a high-risk group. 4 figures, 12 tables, 104 references.
Federally Funded Research on Colon Cancer The U.S. Government supports a variety of research studies relating to colon cancer. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration
2
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database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to colon cancer. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore colon cancer. The following is typical of the type of information found when searching the CRISP database for colon cancer: ·
Project Title: A HIGH THROUGHPUT ASSAY TARGETING BETA CATENIN AND TCF Principal Investigator & Institution: Sussman, Daniel J.; Assistant Professor; Obstetrics and Gynecology; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2001; Project Start 01-MAR-2001; Project End 28-FEB-2003 Summary: Colon cancer is one of the most common forms of cancer in the Western world. The predominant initial genetic events leading to colorectal tumors are mutations in either the adenomatous polyposis coli (APC) tumor suppressor gene or beta-catenin. These mutations result in the stabilization of cytosolic beta-catenin and subsequent association with the LEF/TCF transcription factors, leading to changes in gene expression. Several studies validate TCF mediated transcription as a potential target for colon cancer treatment. The objective of this proposal is to identify compounds that block LEF/TCF mediated transcription using a high-throughput cellbased assay. We intend to use computer-aided rational drug design to screen for compounds with the potential to interact with the Armadillo repeat region of betacatenin, the site at which TCF binds to form a transcriptional activator. Following assay development, optimization and validation, the assay will be used to screen the putative beta-catenin- interacting compounds, as well as a pilot screen of the NCI Natural Products Repository. The high-throughput assay will utilize the HT-29 cell line, a human colon carcinoma in which both APC alleles are truncated. We will generate a line of HT-29 cells expressing destabilized green fluorescent protein variants dECFP and dEYFP, under the control of TCF dependent and TCF independent promoters. This cell line will be used to optimize conditions for monitoring the fluorescent proteins in live cells using a 96-well microplate reader. The dECFP and dEYFP proteins have short halflives and can be detected and quantified independently in the same cell. This will allow us to screen for compounds that specifically turn off TCF-dependent transcription and eliminate those that have no effect, cause a general down-regulation of transcription, or are toxic. The assay has the potential to detect compounds that can disrupt TCF-specific transcription at multiple sites, including blocking beta-catenin/TCF interaction, interfering with the transcriptional activation domain, as well as increasing beta-catenin turnover. A variety of tumors are caused by mutations resulting in the stabilization of beta-catenin, including melanoma, esophageal, gastric, hepatoblastoma and medulloblastoma, as well as others. The lead compounds identified using the above assay, could potentially be useful in treating these other tumors as well as colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
(FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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Project Title: VECTOR
ADENOVIRUS
REPLICATION-COMPETENT
ANTI-CANCER
Principal Investigator & Institution: Wold, William S.; Professor and Chairman; Virrx, Inc. 1609 Adgers Wharf Dr St. Louis, MO 63017 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 30-JUN-2004 Summary: (provided by applicant): We have developed several tumor-specific and tissue-specific replication-competent adenoviruses (Ad) vectors for cancer gene therapy. One vector, named KD3, has a mutation in the E1A gene such that KD3 cannot replicate in, and destroy, "normal" cells. However, KD3 can replicate in cancer cells because they have a microenvironment conducive to KD3 replication. KD3 is efficient in lysing cells and spreading from cell-to-cell, because it overexpresses a protein named ADP which enhances cell lysis. A second vector, named GZ3, is identical to KD3 except it has a wildtype E1A gene. GZ3 is very cytolytic, but it is not tumor-specific and could not be used in its present form to treat cancer. In the past year, we have continued in our attempt to develop optimal vectors to treat cancer. We have constructed new vectors, named KD3COL and GZ3-COL, where the E4 promoter is replaced by a colon cancer-specific promoter named COL. These Ad vectors replicate in colon cancer cells but not other types of cells. We have also constructed vectors named KD3-TERT and GZ3-TERT, which have the E4 promoter replaced by the TERT promoter for telomerase. These vectors should replicate in telomerase-positive cancer cells but not in normal cells. We have also constructed a version of KD3 that secretes an apoptosis-inducing protein without precluding the replication of the vector. This vector should destroy tumors by two mechanisms, vector lytic replication and apoptosis of uninfected cells surrounding the infected cells. Hopefully, the secreted protein may be able to induce apoptosis in tumors that have metastasized. We propose to characterize KD3-COL, GZ3-COL, KD3TERT, GZ3-TERT, and the apoptosis-inducing vector in cell culture, with the primary aim of ascertaining their specificity to cancer cells together with their ability to replicate and spread in these cells. They will also be evaluated for their ability to destroy or suppress the growth of human cancer cells in immunodeficient nude mice. These tumors will be examined with respect to their growth, pathology, and ability to support vector replication. The toxicity and distribution of these vectors in mice will be studied. PROPOSED COMMERCIAL APPLICATION: Cancer is the second leading cause of death in the USA. The adenovirus anti-cancer vectors that wwe have developed are expected to provide effective treatment of many different types of cancers, including colon and prostate. Accordingly, the market potential is extremely large. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: ADJUVANT NUTRITION IN CHEMOTHERAPEUTIC RESPONSE Principal Investigator & Institution: Muga, Stephanie; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, SC 29208 Timing: Fiscal Year 2002; Project Start 29-SEP-2002; Project End 31-AUG-2007 Summary: Colorectal cancer remains a pre-eminent health concern in the United States today and is increasing in incidence worldwide. While chemotherapy for colon cancer is virtually standardized in this country (5-fluorouracil (FUra) and leucovorin), the reasons for only a 30-40% response rate are poorly understood. One highly under-explored variable in cancer chemotherapy is the effect of the patient's nutrient or dietary profile at the initiation of therapy and duration throughout therapy; dietary modification may significantly alter chemotherapeutic response. This project focuses on devising methods to prevent, treat, and control the development and progression of colorectal cancer. The
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novel approach to be explored in this project combines standard chemotherapeutic treatment with diet and nutrition modification to maximize drug efficacy thereby maintaining balances between key biochemical events that regulate cellular growth and differentiation. To date, very little research has examined the impact of dietary modulation on drug efficacy. This project will explore the effects of modifying the dietary environment in improving the response to FUra in a human colon cell culture system and the Ape Min/+ mouse model. Recent experiments in mice have shown that a diet high in fat, and low in vitamin D, calcium, methionine, choline, and folate induced colon cancer in the absence of a carcinogen. Studies on the chemopreventive elements in the diet indicate that many nutrients and non-nutrient components of diets are chemopreventive. We hypothesize that a diet enriched in chemopreventive factors (folate, calcium, vitamin D, and conjugated linoleic acid (CLA)) will potentiate the therapeutic ratio of FUra in the Apc Min/+ mouse. We postulate that a "cancer preventive" diet will enhance FUra-induced programmed cell death (apoptosis) in the colon, whereas a Western Stress diet will inhibit the effects of FUra treatment. In Aim 1, we will identify the molecular mechanisms by which pro-apoptotic dietary factors modulate the therapeutic efficacy of 5-fluoro-2'-deoxyuridine (FdUrd; nueleoside derivative of FUra) by examining biomarkers related to inflammation, proliferation, differentiation, and apoptosis in human colon cancer cell lines. In Aim 2, we will evaluate the therapeutic efficacy of administration of FUra on tumor incidence in the Apd Min/+ mouse. In Aim 3, we will evaluate the effects that (1) a supplemented diet enriched in folate, calcium, vitamin D, and conjugated linoleic acid and (2) a diet deficient in these factors has on 5-FU efficacy in the Apc Min/+ mouse. Results from this work will provide novel insight into the mechanisms of how dietary factors benefit colon tumorigenesis and how these dietary agents influence the ability of FUra to modulate colon carcinogenesis. Data obtained from these studies will be used to generate NIH R01 funding. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: AGONISTS OF GUANYLATE CYCLASE RECEPTOR FOR COLON CANCER Principal Investigator & Institution: Shailubhai, Kunwar; Synergy Pharmaceuticals, Inc. 2 Executive Dr, Ste 450 Somerset, NJ 08873 Timing: Fiscal Year 2002; Project Start 05-APR-2002; Project End 31-MAR-2003 Summary: Recently, we as well as other investigators have demonstrated that the expression of uroguanylin, a peptide hormone produced in the gastrointestinal tract (GI), is dramatically suppressed in colon polyps and tumor tissues. Further, we also demonstrated that the oral administration of uroguanylin inhibits formation of polyps and their progression to adenocarcinoma in Min-mouse, an animal model for colon cancer. Although the precise mechanism is still not clear, we believe uroguanylin binds to guanylate cyclase C (GC-C) and stimulates intracellular production of cyclic guanosine monophosphate (cGMP), resulting in activation of cystic fibrosis transmembrane conductance regulator (CFTR). Activation of CFTR chloride channel proteins and the subsequent enhancement of transepithelial efflux of sodium (Na+), potassium (K+), chloride and water leads to loss in cell volume, which results into inhibition of proliferation and in induction of apoptosis in enterocytes. Subsequently, we also demonstrated that uroguanylin treatment activated caspase-3, a pro-apoptotic enzyme, in human colon cancer cells (T-84). Human uroguanylin has been shown to exist in two isomers (conformational families), and only one of which is biologically active. We will develop novel agonist peptides with rigid three- dimensional structure
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that stabilizes only the conformational family, which is biologically functional. In Phase I of this SBIR Grant, a series of peptide analogs will be developed, based on conformational design, and evaluated in in vitro assays for inhibition of cell proliferation, induction of apoptosis and activation of pro-apoptotic nucleases (caspase3). The overall goal of the proposed study is to develop novel analogs of UG that have longer half-lives, better stabilities, and thereby higher potencies. Accomplishment of this goal will identify a lead peptide for further evaluation in animal models for colon cancer and in human patients is part of a planned Phase II SBIR program. Given the need to find specific colon cancer drugs, the introduction of guanylate cyclase agonist as prophylactic and/or therapeutic agents for treatment of colon cancer is extremely important. PROPOSED COMMERCIAL APPLICATIONS: This research may lead to a drug, or drugs for prevention, treatment and delay in onset of colorectal cancer, which is one of the leading causes of cancer-related deaths in the U.S. Current chemo- and radiation therapies do not discriminate between normal and metastatic, resulting in severe side effects and dose limiting toxicities. We believe that the systemic administration of UG-like peptides will specifically induce apoptosis in cells in colon cancer tissues and also delay in progression of polyps into adenocarcinoma in gastrointestinal tract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: ALTERNATIVE ESTROGEN REPLACEMENT THERAPY FOR COLON CANC* Principal Investigator & Institution: Campbell-Thompson, Martha L.; Pathology, Immunol & Lab Med; University of Florida Gainesville, FL 32611 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 01-JUN-2005 Summary: (provided by applicant): Botanical products are becoming increasingly popular as alternatives to estrogen replacement therapy (ERT). Clinical evidence strongly supports an association between ERT and reduced risk of colon cancer in postmenopausal women. After follow-up of women taking combined estrogenprogestin replacement therapy, the Women's Health Initiative recently reported a 37% reduction in colorectal cancer cases compared to women on placebo. In another 20 published studies, half support an inverse association and another quarter shows a significant reduction in risk. Despite these findings, few investigations are underway to determine the mechanisms by which this preventive effect is achieved. Estrogenic effects are mediated by binding to a nuclear receptor and we determined that the second estrogen receptor subtype, ERbeta, is the subtype found in the colonic epithelium. Our studies also showed reduced expression of ERbeta mRNA in colon tumors compared to normal mucosa in female patients. Furthermore, following over-expression of ERbeta, human colon cancer cells displayed reduced proliferation rates and anchorage independent growth. These data imply that ERbeta could mediate the chemoprotective effects for ERT. The overall hypothesis being tested is that alternative ERT based on phytoestrogens with high ERbeta binding activity will reduce colon carcinogensis. Specific aims are proposed to test the following hypotheses: (1) Overexpression of ERbeta in human colon cancer cells will decrease tumorigenic phenotype in vitro (cells in culture) and in vivo (xenograph growth in mice) by interference of EGFR signaling pathways, and (2) A phytoestrogen-enriched diet will reduce experimentally induced aberrant crypt foci by decreasing proliferative activity in the colonic epithelium. The goal of this application is to define how activation of ERbeta-mediated responses can modulate human colon cancer cell growth and whether a red clover extract with ERbeta-selectivity can decrease carcinogen initiated colon tumorigenesis. If
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phytoestrogens show a chemopreventive effect on colon cancer development and the mechanism is related to ERbeta, these data would clearly expand our understanding of colon cancer and provide a new therapeutic strategy. The ability to pinpoint how an alternative ERT inhibits the adenoma-carcinoma sequence could also lead to more effective methods in preventing cancer recurrence in female patients, as well as developing better chemoprevention strategies in post-menopausal women. The clinical translational potential of this hypothesis lies in the ability of ERbeta positive epithelial cells to respond to phytoestrogens. These results would also suggest additional potential for chemoprevention strategies based on selective estrogen receptor (ERbeta) therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: ANIMAL MODEL FOR HER-2/NEU SPECIFIC TCR GENE TRANSFER Principal Investigator & Institution: Nishimura, Michael I.; Associate Professor; Surgery; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): There are limited treatment options for patients with advanced cancer. Current therapies include surgery, chemotherapy, and radiation therapy. These treatments are relatively ineffective and have considerable morbidity associated with them. An alternative treatment strategy that has been successful for many melanoma and renal cell carcinoma patients is immunotherapy. So far, immunotherapy has not been well tested in breast and ovarian cancer patients. The major factors which have limited the development of immunotherapy for most cancers is there are the lack of T cell antigens expressed by cancer cells and that the antigens identified so far are poorly immunogenic. One antigen that has been extensively studied as a potential target for immunotherapy for many cancers is the proto-oncogene Her2/neu. Several groups have reported isolating Her-2/neu reactive T cells that recognize a variety of cancers including breast, colon, and ovarian cancer. However, early clinical trials in patients vaccinated with antigenic Her-2/neu peptides failed to elicit an effective anti-tumor immune response. Since most immunotherapy strategies are totally dependent on boosting the host anti-tumor immune response, attempts to boost the anti-tumor immune response to weakly immunogenic antigens expressed by cancer cells such as Her-2/neu have proven to be ineffective against breast, ovarian, lung, and colon cancer. We have developed an alternative strategy for providing antitumor reactivity to cancer patients which does not require boosting the host anti-tumor immune response. Using retroviral vectors encoding T cell receptor (TCR) genes, we have been able to transfer the specificity of tumor reactive T cell clones to normal peripheral blood T cells. The goal of this proposal is to determine if normal peripheral blood T cells can be engineered to recognize Her-2/neu+ breast, ovarian, lung, and colon cancer cells and to evaluate therapeutic the efficacy of TCR transduced T cells in treating established Her2/neu+ tumors in mice. Successful completion of these goals may lead to a new treatment for cancer patients with Her-2/neu+ tumors using autologous TCR gene modified T cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: APOPTOSIS IN COLON CANCER CHEMOPREVENTION Principal Investigator & Institution: Gerner, Eugene W.; Professor; None; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2001; Project Start 01-JUL-1997; Project End 31-DEC-2005
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Summary: APPLICANT'S Colon cancer remains the second leading cause of cancer death in the United States of America, affecting both males and females. The major theme of this program is the study of apoptosis in colon carcinogenesis and colon cancer chemoprevention. Studies in experimental rodent models and humans indicate that genetic and intestinal luminal risk factors decrease cell turnover, in part by decreasing apoptosis, in normal and neoplastic colonic tissues. Intestinal luminal risk factors include the secondary bile acids, which are affected by both genetic and dietary factors. Our program addresses both genetic and intestinal luminal risk factors, as we hypothesize that common signaling and metabolic pathways downstream of both these factors mediate cell turnover in colonic tissues and, subsequently, colon cancer risk. A corollary of this hypothesis is that these downstream pathways are rational targets for colon cancer chemoprevention strategies in humans. To test this hypothesis, we have designed projects and cores that are interactive and complementary. One project studies biochemical effectors of genes, including the Ki-ras oncogene and the APC and p53 tumor suppressor genes, which are frequently mutated in human colon cancers. A second project focuses on the role of nitric oxide in bile acid induced apoptosis. The third project emphasizes studies of the AP-1 transcription factor, which is involved in signaling pathways mediated by both APC and bile acids. The specific aims of the projects are to determine the roles of genetic and intestinal luminal risk factors in cell turnover in colonic tissues, to describe mechanisms underlying these processes, and to investigate the consequences of specific pharmacological and/or dietary interventions on cell turnover and colon carcinogenesis. The projects will address these aims using genetically altered cell culture and rodent models of colon cancer, and a variety of biochemical, molecular and cellular biology technologies. Four cores provide support in cell and tissue pathology, breeding and maintaining genetically altered rodent models of colon carcinogenesis, biometry and administration and evaluation. The long-term goal of the Apoptosis in Colon Cancer Chemoprevention Program Project Grant is to understand mechanisms of colon carcinogenesis in humans and then to use this information to establish the rational for strategies of colon cancer prevention and/or treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: BETA CATENIN PATHWAY AND CHEMOPREVENTION BY TEA Principal Investigator & Institution: Dashwood, Roderick H.; Associate Professor; Oregon State University Corvallis, OR 973391086 Timing: Fiscal Year 2003; Project Start 17-MAR-2003; Project End 28-FEB-2008 Summary: There is interest in the possible health benefits of tea against chronic diseases, including cancer. This proposal tests the hypothesis that the inhibitory mechanisms of tea in the GI tract involve the beta-catenin/Apc pathway and expression of betacatenin/Tcf target genes. Most of the work uses a rat model of colon cancer in which the heterecyclic amine -amino-1-methyl- 6-phenylimidazo[4,5-b]pyridine (PhIP) or 1,2dimethylhydrazine (DMH) are the initiating agents. Other studies in humans, Apc rain mice, and rainbow trout examine inhibition by tea according to the following aims: Aim 1. BLOCKING EFFECTS OF TEA - 1A. Compare the efficacy of white tea and green tea, and their major constituents, as blocking agents against PhIP-induced aberrant crypt foci (ACF) and colon tumors in the rat. 1B. Examine during the initiation phase the spectrum and frequency of Ctnnbl (beta-Catenin) and Apc mutations in ACF and colon tumors after tea treatment. 1C. Demonstrate a protective effect of tea, decaffeinated tea, caffeine and chlorophyllin in people consuming a dietary-relevant dose of PhlP. Aim 2. SUPPRESSING EFFECTS OF TEA - 2A. Compare the efficacy of white tea and green tea
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during the post-initiation phase of PhlP- and DMH-induced colon carcinogenesis. 2B. In the tumors from 2A, examine the spectrum and frequency of Ctnnbl and Apc mutations, and the expression of beta-catenin and beta-catenirdTcf/Lef target genes (cyclin D1, cjun, c-myc). 2C. In Apc min mice, show that tea suppresses intestinal tumorigenesis via downregulation of beta-catenin. 2D. Using the trout methylazoxymethanol acetate model, examine the dose-response for tumor suppression by tea, caffeine, and EGCG. Aim 3. BLOCKING AND SUPPRESSING MECHANISMS - 3A. Examine blocking mechanisms of tea, focusing on (i) degradation of ultimate carcinogens, (ii) inhibition of CYP1A2+NAT, and (iii) induction of UDPGT. 3B. In human colorectal cell lines and cells expressing mutant beta-catenins (i) show that tea downregulates beta-catenin and betacatenin/Tcf target gene expression, (ii) examine the relative efficiency of phosphorylation and ubiquitination of beta-catenin, and assembly of beta-catenin/Tcf on target genes, in the presence of tea, (iii) demonstrate that beta-catenilg/Tcf-mediated activation of c-jun and cyclin D1 can be overcome by inhibitory actions of tea on AP-1 and CDK's, and (iv) examine the dose-response for cell cycle attest versus apoptosis in cells expressing wt and mutant beta-catenins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: BETA-CATENIN/NF-KAPPABETA AND COLON CANCER Principal Investigator & Institution: Umar, Shahid; Internal Medicine; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, TX 77225 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Increased rates of proliferation form the earliest and, most probably, the necessary background for the transformation of a normal colonic epithelium to cancer. Chronic intestinal inflammation, especially of the colon, also significantly increases risk of developing cancer. However, the complex interrelationships among inflammation, proliferation and neoplasia generation, is less well understood. We have employed a mouse model (Transmissible Murine Colonic Hyperplasia, TMCH) to study how pro-inflammatory cytokines and dietary butyrate regulate nuclear factor-(B (NF-(B) and (-catenin mediated increases in cell census in the native colonic mucosa. TMCH is characterized by epithelial hyperproliferation and hyperplasia. Depending upon the genetic background, varying degrees of inflammation occur with pathophysiological similarities to human inflammatory gastrointestinal diseases. In outbred mice, onset of TMCH was preceded by transient increases in TNF-( and IFN-(, and parallel mitogenic changes in mucosal ((-catenin abundance, phosphorylation and downstream targets (cyclin Dl, c-myc) signaling. Changes in NF-(B activity /nuclear translocation followed TNF-( expression. Dietary pectin (source of butyrate) abrogated the hyperplastic responses during TMCH. In genetically susceptible C3H/HeNHsd (C3H) inbred mice, a chronic inflammation associated with dramatic increases in intra-epithelial CD3+/CD 103+ T cells, could be seen in the entire colon. Based on these findings, we aim to: 1. Determine how TNF-( and butyrate modulate (catenin/NF-(B expression/activity, sub-cellular distribution, and signaling in the noninflamed colonic mucosa; 2. Determine how TNF-( and butyrate modulate (-catenin/NF(B expression/activity, subcellular distribution, and signaling during chronic inflammation. To accomplish these goals, we intend to utilize in vivo neutralizing TNF-( antibody and direct colonic mucosal exposure to Eudagrit coated sodium butyrate pellets. These studies will help us delineate how TNF-( and butyrate individually modulate (-catenin/NF-(B mediated hyperproliferation /inflammation and subsequent mucosal priming for carcinogenesis. By studying a mechanistic basis of NF-(B and (-
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catenin mediated increases in cell census, in the absence and presence of chronic inflammation, we may identify new treatment strategies for reducing cancer risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: BILE ACID INDUCED AP1 SIGNALING IN COLON CANCER Principal Investigator & Institution: Martinez, Jesse D.; Associate Professor; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2001; Project Start 01-JUL-1997; Project End 31-DEC-2005 Summary: APPLICANT'S The overall objective of this project is to delineate the mechanism through which bile acids alter colon tumor etiology by examining the effect that bile acid-mediated changes in signal transduction and gene expression have on cell fate. Deoxycholic acid (DCA) can stimulate gene expression by activating the AP-1 transcription factor through up regulation of the ras/erk pathway, suggesting that DCA acts as a tumor promoter by aberrantly up regulating protooncogene activity and mimicking the effects of gene mutations. Interestingly, DCA also stimulates a separate protein kinase C-dependent pathway that may also cause up regulation of AP-1 through GSK-3 in the Wnt-1 signaling pathway. Interestingly, ursodeoxycholic acid (UDCA), a bile acid with chemopreventative properties, does not stimulate AP-1 activity. Instead, UDCA stimulated signaling cooperates with activated AP-1 and/or PKC signaling to induce apoptosis. Importantly, we have determined that AP-1 may be up-regulated in Min(+) mouse tumors and in the flat mucosa of AOM treated mice long after final exposure to this carcinogen, suggesting that AP-1 is aberrantly activated in vivo under conditions that foster tumor development. Consequently, we hypothesize that bile acids modulate colon cancer etiology by altering signal transduction that leads to activation of AP-1. Furthermore, we speculate that UDCA may function as a chemopreventive agent by selectively inducing apoptosis in cells where AP-1 and/or PKC is aberrantly stimulated. We will test this by: 1) determining whether DCA can modify the activity of and/or dysregulate Wnt-1 signaling, 2) examine the effect of germline mutations in the APC gene on tumor promotion/chemopreven-tion by bile, 3) characterize UDCAmediated signaling activity in colon-derived cell lines, 4) determine whether UDCA can induce apoptosis in colonic epithelial cells with aberrant AP-1 activity, 5) Examine the effect that a diet supplemented with UDCA has on signal transduction and gene expression in the colonic epithelium of human subjects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BILIVERDIN IN MELANOMA CELL DIFFERENTIATION Principal Investigator & Institution: Falchuk, Kenneth H.; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: We reported that biliverdin is required for formation of eyes, brain, spinal cord and other dorsal organs in amphibia. Beyond that mandatory requirement for embryogenesis, we found that biliverdin is a pleiotropic molecule capable of altering the phenotypes of a number of cancer cells to a more differentiated state. An early and common behavior caused by biliverdin is an arrest of proliferation in six cancer cells (melanoma, colon adenocarcinoma, liposarcoma, thyroid carcinoma, T and B cell lymphomas). In colon adenocarcinoma, the c Myc oncogene disapp9ears within two days of incubating with 5 x 10-7 M biliverdin. Concurrently, biliverdin slows their G1 to S transition. Subsequently, two differentiation markers, CEA and alkaline phosphatase, are up-regulated. These findings suggest that biliverdin reverses the phenotypic
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consequences of APC and beta catenin mutations characteristic of colon adenocarcinoma. Central to the current proposal are the documented findings that, like in colon adenocarcinoma, melanoma cells characteristically exhibit mutations in the same signaling system including GSK3beta phosphorylation sites of beta catenin and/or abnormally expressing high amounts of beta catenin itself. These mutations and overexpression lead to an increase in stable cytoplasmic beta catenin and enhanced transcription of beta catenin/Tef/Lef oncogenes, such as c Myc. The common alterations in beta catenin signaling found in colon cancer and melanoma cells calls for examination of the possibility that the dermatological malignancy also may be responsive to the effects of biliverdin and be directed along a differentiation pathway. In favor of this premise is a) our finding that biliverdin arrests cell division if SJ NEK 24 melanoma cell and b) literature reports that 12-o-tetra decanoyl phorbol 13 acetate (TPA), a molecule that up-regulates heme oxygenase 1 (HO 1) in cancer cells and, therefore, must lead to an increase in biliverdin content of these cells, also inhibits proliferation of melanoma cells. Consequently, we propose to examine the effect of biliverdin on SK MEL 24 phenotype focusing on oncogene molecules transcriptionally regulated by the beta catenin signaling system (Aim 1) and on beta catenin itself and GSK3beta, the enzyme responsible for its phosphorylation and degradation (Aim 2). These two aims will be examined by incubating the SK MEL 24 cells with biliverdin. If the results are positive, we will examined these same molecules in SK MEL 24 cells induced to synthesize biliverdin in response to phenylarsine oxide, a known activator of heme oxygenase 1 (Aim 3). Positive results will demonstrate that melanoma cells can be made to undergo differentiation and open the door to possible novel therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: BIOADHESIVE MICROSPHERES FOR COLON CANCER THERAPY Principal Investigator & Institution: Egilmez, Nejat K.; T & B Bioclone, Inc. Eden, NY 14057 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JAN-2003 Summary: A novel drug and cytokine delivery system is being tested for its ability to prevent and/or suppress spontaneously arising intestinal tumors. Biodegradable microspheres are specifically formulated to achieve a strong adhesion to intestinal epithelium. Following their loading with either sulindac (a nonsteroidal antiinflammatory drug with antitumor activity) and/or Interleukin-12 (a potent immunostimulatory cytokine) the efficacy of the microspheres to deliver a drug or cytokine to the site of tumor development and to promote an antitumor effect is evaluated in a murine model (C57Bl/6J-Min) in which multiple intestinal tumors arise spontaneously as a result of a mutation in the murine homolog of the human adenomatous polyposis coli (APC) gene. The effectiveness of delivery with bioadhesive microspheres is compared to that obtained with bolus delivery of the free drug and/or cytokine. The antitumor efficacy of the therapy is evaluated a) in a prophylactic setting where young mice are treated with sulindac-loaded microspheres prior to tumor development, and b) at a later stage with sulindac and/or IL-12-loaded microspheres when they have established tumors. Local and sustained delivery of the drug by the microspheres to the intestinal epithelium is expected to improve the antitumor activity of sulindac and to prevent the growth of tumors while the ability to target IL-12 to the tumor milieu is expected to suppress tumor growth, prolong survival and induce antitumor immunity. If successful, these data will provide the requisite rationale for initiating a phase I clinical trial. PROPOSED COMMERCIAL APPLICATIONS: The local and sustained release of cytotoxic drugs and biologically active molecules such as JL-12
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at the tumor site is expected to enhance the anti- tumor activity of drugs and cytokines and decrease their toxic effects upon normal tissues that occur when given systemically. The microspheres, that are protected by patents, provide a simple and much less expensive alternative to gene therapy for cytokine delivery and they can locally deliver drugs and cytokines simultaneously. These biodegradable, non-toxic microspheres if proven effective here for either prevention or treatment of colon cancer would have a significant market potential since colorectal cancer is the third most common cause of cancer related deaths in the United States. Additional potential markets are anticipated for this novel delivery system in the application of this technology to other tumors and for the local and sustained delivery of other drugs that are toxic when delivered systemically as bolus injections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: BIOCHEMICAL MARKERS IN THE NURSES' HEALTH STUDY COHORT Principal Investigator & Institution: Hankinson, Susan E.; Associate Professor; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 01-JUN-1989; Project End 31-MAR-2004 Summary: We propose to analyze blood samples in a nested case-control manner from the 32,826 participants in the Nurses' Health Study (NHS) who provided samples in 1989-90 and were 43 to 69 years of age at that time. The samples have been stored at greater than or equal to 130 C in liquid nitrogen freezers since collection. We will assay samples from women who were diagnosed after blood collection and matched controls who remained disease-free, thus efficiently utilizing these prospectively collected samples. We propose to build upon our recent positive findings for several plasma hormones and nutrients in relation to breast and colon cancer risk, and to address new hormonal hypotheses in relation to risk of breast, ovarian and colon cancers and myocardial infarction. Specifically, we will examine (1) plasma estrogens, androgens and prolactin levels in relation to breast cancer risk in postmenopausal women, (2) a polymorphism in the catechol-O- methyl transferase (COMT) gene and risk of breast cancer, (3) DHEA, DHEAS and 5-androstene-3beta,17beta-diol and risk of breast and ovarian cancers and myocardial infarction, (4) insulin-like growth factor I and its binding proteins 1 and 3, plasma vitamin D and polymorphisms in the vitamin D receptor, and plasma antioxidant levels - all in relation to risk of breast and colon cancers. The ongoing NHS (CA40356 and HL34594) will provide follow-up and documentation of disease outcomes in addition to providing information on important covariates (such as exogenous hormone use, diet, smoking status, among others) for the proposed study. Participation in the NHS has been high: among the 32,826 women who provided a blood sample, 98 percent continue to complete questionnaires, and vital status has been documented for 99 percent. Overall, the large size of the cohort, the prospective design, the high follow-up rate, the detailed exposure data, and the availability of archived blood specimens provide a unique opportunity to test several hypotheses of public health importance. We also propose to collect a second blood sample from about 18,000 of the women who provided a first blood sample in 1989-90. This will increase our statistical power in future analyses, and allow us to assess in detail the temporal relationships between biomarkers and disease risk and to reduce the attenuating effects of measurement error. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOLOGICAL EVALUATION OF ZD1839 IN COLON CANCER Principal Investigator & Institution: Hidalgo, Manuel; Associate Professor of Oncology; Oncology; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2002; Project Start 09-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The epidermal growth factor receptor (EGFR) is a transmembrane receptor involved in the transduction of proliferative and survival signals which is overexpressed in up to 50 % of patients with colon cancer. Preclinical data suggest that pharmacological inhibition of the EGFR results in tumor growth inhibition and, therefore, the EGFR represents a potential target for cancer therapy. ZD1839 is a novel, orally available, small molecule inhibitor of the EGFR in clinical development. Important questions in the development of this agent, as well as other mechanistic based compounds are the definition of patient populations more likely to respond to the drug based on the presence and functionality of the target pathway in tumor tissues and the assessment of target inhibition in clinical trials. This proposal outlines a series of clinical, pharmacological and biological studies of ZD1839 in patients with colon cancer. Our long term goal is to develop ZD1839 for the treatment of patients with colon cancer, as well as with other EGFR-driven tumors, utilizing rationally derived biological concepts based on the putative mechanism of action of the agent. The specific aims of this proposal are: Specific Aim # 1: to determine the relationship between expression and activation of the EGFR receptor in malignant tissues and the activity of ZD1839 in patients with colon cancer, Specific Aim # 2: to characterize the effects of ZD1839 on the activation and signaling of the EGFR in tumor and normal tissues of patients with colon cancer who are treated with ZD1839; and, Specific Aim # 3: to relate the pharmacodynamic effects of ZD 1839 to relevant indices of clinical activity. Patients with advanced, measurable, colon cancer will be treated with ZD1839 at a dose of 500 mg/day on a protracted oral dosing schedule. Tumor tissues, normal skin tissues, and plasma will be collected at baseline and 28 days post-treatment. The expression and activation of the EGFR will be determined using validated immunohistochemical methods developed at our institutions. The result from the biological studies will be correlated with indices of drug activity. These results will provide hypothesis-generating data regarding the subset of colon cancer patients more likely to benefit from treatment with this agent as well as information regarding the biological activity of ZD1839 in colon cancer. Collectively, these data will impact in the future development of ZD1839 in patients with colon cancer as well as other tumor types. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOLOGY AND PATHOLOGY OF A MODULATOR OF FGF Principal Investigator & Institution: Wellstein, Anton; Professor; V T Lombardi Cancer Res Center; Georgetown University Washington, DC 20057 Timing: Fiscal Year 2001; Project Start 01-JUN-1997; Project End 30-NOV-2005 Summary: (Applicant's Abstract): Fibroblast growth factors (FGF-1 or -2) are present at significant concentrations in most normal tissues in the adult. However, these FGFs are immobilized in an inactive state on the extracellular matrix and it is only poorly understood how they are solubilized and activated to reach their receptors. These growth factors can be mobilized by a previously identified secreted binding protein for FGF (BP1). We showed that the retinoid-regulated BP1 can enhance the activity of locally stored, immobilized FGFs and that expression of BP1 supports tumor growth and angiogenesis of FGF-2 positive non-tumorigenic cells. A recently identified novel
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BP2 showed similar biologic activities. In preliminary studies we found that addition of BP1 protein enhances FGF effects in different biological assay systems. Furthermore, expression of the BP1 cDNA was embryonically lethal in transgenic mice and caused vascular leakage in chicken embryos. BP mRNA was below detection in normal adult human or murine tissues but was detectable in murine embryonic gut and skin. Carcinogen treatment upregulates BP1 in adult mouse skin and in carcinogen-treated human skin xenografts in SCID mice. BP1 was expressed in squamous cell cancer (SCC) patient samples and cell lines as well as in colon cancer cell lines and tumor samples. In contrast, BP2 appears to be upregulated only in melanoma and was not detected in the tumor types expressing BP1. Inhibition of tumor growth was observed in human ME180 (SCC) and Ls174T (colon cancer) cell lines in which the endogenous BP1 levels had been reduced with BP1-targeted ribozymes. This finding in conjunction with the expression of BP1 in human cancer samples suggests a rate-limiting role of BP1 for the malignant phenotype of SCC and colon cancer. We plan the following studies: Under aim 1 we propose a series of experiments to map the BP / FGF protein / protein interactions to define these interactions at the atomic level. Under aim 2 we will define the effects of BPs and interaction with heparansulfate on the effects induced by FGFs in cells and tissues. Under aim 3 we will use ribozyme-targeting of BP mRNA to assess to what extent expression of the BP2 is rate limiting for the tumorigenic phenotype of melanoma and to what stage of tumor growth and metastasis BP2 and BP1 contribute most significantly. Under aim 4 we will study the effect on BP1 expression in transgenic mice and chicken embryos. Tissue-selective vectors and conditional tetracyclinedependent expression will be used to circumvent embryonic lethality of BP1 expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: BIOMATHEMATICAL APPROACHES TO CANCER Principal Investigator & Institution: Moolgavkar, Suresh H.; Professor; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, WA 98109 Timing: Fiscal Year 2002; Project Start 01-MAR-1988; Project End 30-JUN-2006 Summary: (provided by applicant): Clones of intermediate cells on the pathway to cancer, such as adenomatous polyps and altered hepatic foci, are often observed in humans and animals. These lesions provide insights into the earliest stages of the carcinogenic process. Because clonal expansion of cells that are partially transformed can increase the probability of cancer substantially, a quantitative understanding of these lesions is key to understanding cancer rates. The broad objective of this project is to continue the development of mathematical, statistical and computational tools, within the paradigm of multistage carcinogenesis, for the quantitative analyses of early lesions on the pathway to malignancy. The fundamental goals of these analyses are to study the temporal evolution of these lesions, to estimate the rate of initiation of the lesions, and the rates of cell division and apoptosis of the partially transformed cells that comprise the lesion. Information on such early lesions is typically available from initiationpromotion experiments, particularly in the rodent liver.In previous work mathematical expressions have been developed for the number and size distribution of intermediate lesions on the pathway to malignancy and used for analyses of initiation-promotion experiments in rat liver. This proposal plans to extend this work in light of new biological information. In addition to continuing work on analyses of liver foci in rodents, the research proposed here will investigate intermediate lesions in the human colon and in patients with Barrett's esophagus, a high-risk precursor condition for adenocarcinoma of the esophagus. In addition to the mathematical and statistical problems associated with clonal growth models within the paradigm of multistage
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carcinogenesis, both analyses of liver foci and analyses of lesions in Barrett's esophagus present diverse problems. Recognizing that modeling is an iterative process an integral part of this effort will be collaboration with experimentalists and human biologists, in particular Dr. Michael Schwarz, University of Tubingen, an expert on the rodent liver system, Dr. John Potter, an epidemiologist with expertise on colon cancer and Dr. Brian Reid, Director of the Seattle Barrett's Esophagus Project. The results of analyses will be used to help generate biologically relevant questions and hypotheses and to plan further experiments and studies, which, in turn, will lead to more refined models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: CANCER BIOREPOSITORIES
RESOURCE--PATHOLOGY,
REGISTRY
AND
Principal Investigator & Institution: Aaronson, Stuart A.; Professor and Director; Ruttenberg Cancer Center; Mount Sinai School of Medicine of Nyu of New York University New York, NY 10029 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Rapid advances in technology and scientific knowledge have opened new opportunities for important discoveries in translational research. As a result, it is becoming increasingly important to link tissue characteristics of patients to demographic, pathologic and clinical records, without compromising patients' rights and confidentiality of medical records. This comprehensive approach to research would allow for significant progress in the study of cancer etiology, progression and prognosis from various disciplines at Mount Sinai Medical Center. The overall aim of this proposal is to establish the infrastructure for conducting cancer research with human specimens. The "Cancer Resource: Pathology, Registry, and Biorepository" herein will build upon our existing infrastructure of colon and breast cancer familial registries, Tumor Registry and specimen banks. The aims of the Cancer Resource will facilitate research ranging from basic science to translational research, and to large-scale molecular epidemiologic studies. Specifically, the objectives are: 1) to obtain presurgical consent from patients undergoing surgery for incident or suspected cancer (beginning with breast and colon cancer) to contribute to the DHRCC Data and Biorepository; 2) to establish a comprehensive database with information from consented patients related to pathologic, clinical and epidemiologic data. Follow-up status, conducted by the Tumor Registry, will also be included in this database; 3) to establish a biorepository containing banked serum, plasma and DNA from cancer and high- risk patients and healthy controls for use by investigators with proposals approved by the Advisory Committee, with detailed clinical, pathologic and epidemiologic data available on that population. Repository services (blood processing, aliquoting and storage) will be available for specimen banking for investigators with funded studies; 4) to establish a tissue repository, linked to patient records, with freshly harvested and paraffin-embedded specimens, and to provide histology services (sectioning, immunohistochemical staining and laser capture microdissection) at a reduced cost to cancer researchers. An Advisory Committee will be established to oversee the running of the Data and Biorepositories, and solicit and review the scientific quality of proposals planning to use tissue and blood specimens. This Shared Resource will facilitate ongoing and future studies related to cancer etiology, markers of cancer progression, and prognosis after cancer diagnosis. The availability of data on patient characteristics will be an invaluable resource for translational research using tumor and normal tissue and other biospecimens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CANCER SCREENING COMPLIANCE IN HEREDITARY COLON CANCER Principal Investigator & Institution: Syngal, Sapna; Dana-Farber Cancer Institute 44 Binney St Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 29-SEP-2005 Summary: (Applicant's Description) The success of the effort to decrease colorectal cancer (CRC) mortality is limited by low rates of compliance with screening. Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common cause of hereditary colon cancer. Intensive surveillance beginning at age 25 and/or prophylactic colectomy and annual endometrial cancer screening are recommended in at-risk family members. We have previously shown that surveillance and prophylactic colectomy lead to large gains in life-expectancy for HNPCC patients. However, there are no available data regarding screening compliance rates or use of prophylactic surgery in this high-risk population. In addition, our preliminary data suggest that many patients and physicians are not aware of the need for frequent and early colonoscopy and the need for surveillance for extracolonic tumors in HNPCC. The research projects outlined in this application address several of these factors. We propose to assess compliance with CRC and extracolonic tumor screening in 400 individuals from HNPCC families. Patients will be recruited from a variety of clinical practices ranging from primary care physicians to specialized cancer genetics clinics. We will develop a behavioral intervention that includes health care provider delivered messages, educational materials, reminder postcards and motivational phone calls designed to educate HNPCC patients and promote screening compliance. HNPCC patients who have not undergone recommended colorectal and endometrial cancer screening will be enrolled in a randomized controlled pilot study of the standardized behavioral intervention compared to usual care. Cancer screening compliance and knowledge about HNPCC will then be compared between the usual care and intervention groups. If the intervention appears to be effective in this pilot study, we plan a future multi-center study using established HNPCC registries and co-operative groups. The structure of the intervention and educational materials developed for this study could easily be exported for use in the clinical setting. The research plan and educational curriculum outlined in this proposal and institutional support provided have been designed specifically for the candidate to develop expertise in cancer prevention research related to the genetics and prevention of gastrointestinal cancer and ensure an independent research career. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CANCER SERO EPIDEMIOLOGY AMONG THE JAPANESE IN HAWAII Principal Investigator & Institution: Nomura, Abraham M.; Director; Kuakini Medical Center 347 N Kuakini St Honolulu, HI 96817 Timing: Fiscal Year 2001; Project Start 15-SEP-1983; Project End 30-JUN-2003 Summary: (Adapted from the Investigator's Abstract) This is a sero-epidemiologic prospective study to identify biochemical markers related to common cancers occurring among 11,132 American Japanese subjects examined in Hawaii. Their unthawed serum, obtained many years prior to the diagnosis of cancer, will be used in the investigation. The proposal is focused on five specific cancer sites: prostate, colon, breast, stomach and urinary bladder. Eight specific aims will be addressed: 1) to determine whether low serum isoflavonoid levels increase the risk of prostate cancer; 2) to see if low serum selenium levels increase prostate cancer risk; 3) to determine whether high serum
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insulin level increases the risk of colon cancer risk in men; 4) to find out if low serum isoflavonoid levels increase breast cancer risk in women; 5) to determine whether men carrying the Helicobacter pylori Vac-A strains are at increased risk for stomach cancer; 6) to see if the presence of H. pylori serum markers increase the risk of total and causespecific mortality in men; 7) to find out if serum levels of vitamin A and carotenoids are inversely associated with urinary bladder cancer risk in men; 8) to determine whether low serum selenium levels increase urinary bladder cancer risk in men. The population base for aim 4 consists of 1787 women, born from 1900 to 1935 who were interviewed and examined from 1975-1977. The subjects for the rest of the aims are 9345 men born from 1896 to 1935, who were interviewed and examined from 1971 to 1976. A wealth of epidemiologic-based data was collected on these participants, and they have been under continuous hospital surveillance for cancer since their examination. Two types of study design will be used in this proposal: 1) prospective study (aim 6); 2) nested case-control study (the rest of the aims). It is estimated that the number of incident cases will be as follows: 376 prostate, 387 colon, 120 breast, 293 stomach, and 131 urinary bladder cancer cases. The number of cause -specific mortality cases should be at least 870 coronary deaths, 1277 cancer deaths and 4145 deaths among the men. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: CASE CONTROL STUDY OF STATIN USE AND LARGE BOWEL CANCER Principal Investigator & Institution: Coogan, Patrica F.; Epidemiology and Biostatistics; Boston University Medical Campus 715 Albany St, 560 Boston, MA 02118 Timing: Fiscal Year 2001; Project Start 18-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from applicant's abstract): Cancer of the large bowel is a leading cause of cancer morbidity and mortality in the United States. Our previous epidemiologic studies played a key role in documenting an inverse association between the use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDS) and the incidence of large bowel cancer. Those studies were inspired by laboratory data suggesting that NSAIDs may reduce colon carcinogenesis. Now a growing body of laboratory data indicates that the commonly used, relatively new class of cholesterollowering drugs, the "statins" may have a similar chemopreventive potential: statins inhibit the growth of colon cancer cells in vitro and in vivo. There is also some evidence that statins may enhance the chemopreventive effect of NSAIDS. The statins (e.g., lovastatin, simvastatin) were first marketed in 1987, and are now among the most commonly prescribed drugs in the United States. At this time there is little epidemiologic data concerning their potential protective effect against large bowel cancer. Two randomized trials of statin use as preventives of coronary heart disease had nonsignificant deficits of large bowel cancer in the treated groups. We propose to conduct a population-based case-control study in Massachusetts of the relation of statin use to the risk of large bowel cancer. We will identify 2050 incident cases aged 50-74 through participating hospitals and 2050 age, sex, and precinct matched community controls from Massachusetts town lists. Cases and controls will be interviewed to obtain information on demographic factors, risk factors for large bowel cancer, detailed histories of statin and NSAID use, and data useful for addressing potential biases. The study is large enough to assess the influence of characteristics of statin use (timing, duration, dose) on the risk of large bowel cancer and to assess consistency of findings across subgroups of age, sex, and cancer site. The joint effect of statins and NSAIDs will also be assessed. The proposed study will provide informative epidemiologic data on a potential chemopreventive of large bowel cancer. Because the incidence of the disease
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and prevalence of statin use by U.S. men and women are high, an inverse association would be of considerable public health importance. Moreover, it would shed light on a mechanism of colon carcinogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: CATHEPSINS IN MALIGNANT PROGRESSION Principal Investigator & Institution: Sloane, Bonnie F.; Professor & Chair; Pharmacology; Wayne State University 656 W. Kirby Detroit, MI 48202 Timing: Fiscal Year 2001; Project Start 01-APR-1992; Project End 31-JAN-2005 Summary: There is increasing evidence that malignant progression of human tumors involves proteolytic cascades that are initiated at the tumor cell surface. Two major observations implicate the lysosomal cysteine protease cathepsin B in this process. One is that cathepsin B becomes a cell surface enzyme in tumors. The other is that high levels of expression of cathepsin B correlate positively with aggressive behavior and progression of human tumors and negatively with patient survival. Cathepsin B appears to be a participant as cathepsin B inhibitors and cysteine protease inhibitors reduce tumor cell motility, invasion and growth in vitro and tumor growth and metastasis in vivo. Recent studies have found that cathepsin B expression is dramatically increased in premalignant lesions. This would be consistent with our hypothesis that membraneassociated cathepsin B degrades basement membrane coincident with the transition to malignancy. In this proposal, we will evaluate mechanisms that may result in association of cathepsin B with the tumor cell surface and, using model systems for colon cancer, determine whether this protease participates in degradation of extracellular matrix proteins and invasion in vitro and malignant progression in vivo. In the first aim, we will establish the function of various regions of cathepsin B in its trafficking using cells deficient in cathepsin B or mannose 6-phosphate receptors, and analyze the interactions between cathepsin B and a vacuolar sorting receptor and cathepsin B and putative binding proteins. In the second aim, we will use living colon cancer cells to determine whether: a) cell surface cathepsin B exhibits endopeptidase or exopeptidase activity, and b) cathepsin B is responsible for degradation of extracellular matrix proteins in a novel quenched-fluorescent protein assay. In the third aim, we will manipulate colon cancer model systems to downregulate cathepsin B expression, reduce its cell surface localization or inhibit its activity in order to determine whether cathepsin B is casually linked to colon cancer progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CDX2 TUMOR SUPPRESSOR PATHWAY DEFECTS IN COLON CANCER Principal Investigator & Institution: Fearon, Eric R.; Professor; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 15-AUG-1999; Project End 31-MAY-2004 Summary: The etiological factors and exposures that underlie colorectal cancer development are complex. Nevertheless, in the past decade, clearcut insights into the role of inherited and somatic mutations in colorectal cancer have been obtained. The stepwise accumulation of mutations in oncogenes, such as K-ras, and tumor suppressor genes, such as the APC and p53 genes, is believed critical in initiating adenomatous polyp formation and subsequent progression to fully invasive and metastatic cancer. Despite the considerable progress, additional mutations that underlie colorectal cancer
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development await discovery. Moreover, much work remains if we hope to understand the means by which specific mutations contribute to the cancer cell phenotype. Recent studies indicate that germline inactivation of one allele of an intestinal-specific homeobox gene, known as Cdx2, strongly predisposes mice to the development of adenomatous polyps and cancers in the small intestine and colon. We are particularly interested in determining the biological relevance of this finding with respect to human colorectal cancer. Our preliminary studies indicate that reduced or absent CDX2 expression is seen in a significant fraction of colorectal cancer; CDX2 mutations are present in some cases; and CDX2 alterations appear to arise independently of other gene defects. We have identified several candidate Cdx2-binding proteins that may allow us to define the growth regulatory pathway(s) in which CDX2 functions. The studies proposed in this application will further explore the nature and significance of CDX2 pathway abnormalities in human colorectal cancer. Four specific aims are proposed: I) To carry out comprehensive CDX2 mutational analyses and expression studies in colorectal cancer cell lines, xenografts, and primary tumors; II) To define mechanisms underlying CDX2 gene expression defects in cancer; III) To determine if CDX2 functions as a suppressor of in vitro growth and/or tumorigenesis, and if so, to define CDX2regulated target genes; and IV) To identify Cdx-2 interacting proteins and address their role in cancer development. In addition to furthering our understanding of colorectal cancer pathogenesis, the studies in our application may offer novel insights for improving the diagnosis and treatment of patients with colorectal cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: CENTER FOR COLON CANCER RESEARCH Principal Investigator & Institution: Berger, Franklin G.; Professor; Biological Sciences; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, SC 29208 Timing: Fiscal Year 2002; Project Start 29-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The primary goal of this COBRE proposal is to increase the number of active, NIH-funded biomedical researchers in the State of SC. This will be accomplished through the combined efforts of a number of investigators at the USC who have merged their collective expertise in formation of a multidisciplinary research group studying the biology of colorectal cancer, its therapy, and its prevention. Colorectal cancer is a leading cause of cancer death in the US, with about 150,000 new cases and 56,000 deaths occurring annually. Current pharmacologic regimens provide only marginal benefit in managing the disease, owing to the drug resistance of colorectal tumors, as well as to the toxic side-effects evoked by these regimens. The biomedical scientists who have come together for this application have formed an interdisciplinary center, the Center for Colon Cancer Research (CCCR) that has focused its efforts around the problem of colorectal cancer. The research proposed in the current COBRE application has three aims. The first is to carry out research on specific molecular, biochemical, genetic, and lifestyle factors that impact upon colorectal cancer and its therapy. This will be done by supporting four projects led by promising junior faculty members. The second aim is to provide core facilities in support of these research projects, giving the lead investigators necessary state-of-the-art technical capabilities. The final aim is to manage a program through which the four young faculty, as well as ten new faculty to be recruited during the five-year period of the grant, are mentored by established investigators with substantive records in NIH funding. In all, the COBRE program proposed in this application will have two long-tern1 benefits. First, the number of NIH-competitive researchers in SC will increase. Second, the CCCR will be
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poised to apply for a program project grant in the area of colon cancer. Such grants are few in SC and in other IdeA states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: CLINICAL SIGNIFICANCE OF APOPTOSIS IN COLON CANCER Principal Investigator & Institution: Sinicrope, Frank A.; Associate Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Tumor stage remains the most important prognostic variable in human colorectal cancers and is used to determine the need for adjuvant chemotherapy. However, there is considerable stage-independent variability in clinical outcome. Despite adjuvant treatment, 30-40% of stage III patients will recur and die of their disease. Accordingly, additional prognostic markers are needed to better define the subset of patients who would benefit most from adjuvant chemotherapy. Prognostic and predictive markers would also enable a more selective, tailored and molecularlytargeted treatment approach. We propose to study apoptotic regulatory proteins in >1,000 well characterized stage II and III colon cancers from patients treated in 5fluorouracil-based adjuvant therapy trials conducted by the North Central Cancer Treatment Group (NCCTG) and the National Cancer Institute of Canada. Some of these trials include untreated control arms enabling us to determine predictive utility. Defects in the regulation of apoptosis have been shown to contribute to tumor progression and metastasis, and can confer resistance to anti-cancer therapies. Two distinct apoptotic signalling pathways have been defined and include the membrane death receptor (DR) pathway and the mitochondrial pathway. Engagement of the mitochondrial pathway results in cytochrome release which can be attenuated by anti-apoptotic Bcl-2 and by inhibitors of apoptosis proteins (lAPs), which bind to and inhibit caspases. The DR pathway is engaged by members of the TNF superfamily which act as natural ligands for specific DRs. DRs mediate apoptosis through their cytoplasmic death domains. Decoy receptors lack death domains but can compete for ligand binding. Both apoptotic pathways involve activation of intracellular cysteine proteases known as caspases that become activated through proteolytic processing and lead to apoptosis. Our preliminary data indicate that apoptotic regulatory proteins display tumor-specific overexpression in human colon cancers. Moreover, our data suggest that negative and positive regulators of the mitochondrial pathway are significantly associated with shorter and longer patient survival rates, respectively. Recent data also suggest that DR4 is overexpressed in colon cancers and can confer prognostic information, as can decoy receptor 3, an inhibitor of Fas signalling. We propose to determine the predictive and prognostic significance of apoptotic regulatory proteins in 1,324 colon cancer patients. Tissue microarrays will be created from paraffin blocks to enable the efficient immunohistochemical analysis of multiple apoptosis-regulating proteins Our study results will then be correlated with previously determined markers including microsatellite instability, allelic loss, and DNA ploidy and multivariate models will be created to determine the most significant markers for incorporation into a prospective adjuvant therapy trial involving 3,750 patients to be conducted by the NCCTG/Intergroup mechanism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CLINICAL TRIALS OF FLAVOPIRIDOL WITH CHEMOTHERAPY Principal Investigator & Institution: Schwartz, Gary K.; Associate Professor of Medicine; Sloan-Kettering Institute for Cancer Res New York, NY 10021
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Timing: Fiscal Year 2001; Project Start 01-AUG-1996; Project End 31-DEC-2003 Summary: Despite many recent advances in cancer therapy, it is apparent that with the high rate of treatment failures in gastrointestinal cancers new therapeutic approaches are necessary. An understanding of the cell cycle has provided the opportunity for the identification of new therapeutic targets. Cell cycle checkpoints at the G1/S and the G2/M interface are tightly regulated by a broad range of cell cycle proteins called cyclin dependent kinases (CDK's). In the NCI drug screen the drug flavopiridol has been identified that inhibits CDK1, 2, 4, and 6. However, despite promising preclinical activity, phase II single agent trials with flavopiridol in colon and gastric cancers have been disappointing. In view of this, R01 CA67819-04A1 had been devoted to developing a different therapeutic strategy in the development of flavopiridol for the treatment of gastrointestinal cancers. Our laboratory studies have indicated that flavopiridol enhances the induction of apoptosis by chemotherapy, especially paclitaxel, in human gastroesophageal cancer cell lines. This has been translated into a phase I clinical trial of sequential paclitaxel followed by flavopiridol (MSKCC IRB#96-77 and NCI#T96-0091). The clinical results have been remarkable for major responses in patients with chemotherapy refractory malignancies, especially in patients with esophagus cancer who have received prior paclitaxel therapy. Proving that flavopiridol restores the activity of a paclitaxel in patients with paclitaxel-refractory esophageal cancer would have extraordinary clinical implications. This hypothesis will be tested in a phase II trial. Patients with metastatic esophagus cancer who have demonstrated unequivocal disease progression on prior paclitaxel will receive paclitaxel with flavopiridol. In addition, we plan a phase I clinical trial combining flavopiridol with irinotecan (CPT-11). CPT-11 is a major new drug in the treatment of colon cancer. However, response rates with this agent remain quite low. The basis for treatment failure is unknown. Preliminary clinical results from our Center indicate that increased expression of the CDK inhibitor p21 is associated with CPT-11 resistance. Our laboratory data indicates that flavopiridol significantly potentiates the induction of apoptosis by CPT-11 in colon cancer cell lines and this is associated with the suppression of p21 protein. Therefore, in this phase I clinical trial we propose examining the expression of p21 relative to treatment response and determining whether p21 is suppressed with the drug combination. In addition, we will use representational differential analysis (RDA) to identify new biomarkers of response for this drug combination. The long-term goal of this phase I study will be to increase the therapeutic benefit of CPT-11 and to identify those patients who would most benefit from the drug combination. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: COLON CANCER AND MITOCHONDRIA Principal Investigator & Institution: Heerdt, Barbara G.; Professor; Montefiore Medical Center (Bronx, Ny) Bronx, NY 104672490 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2007 Summary: Abnormal proliferation or apoptotic pathways disrupt homeostasis of the colonic mucosa, modulating risk for, and progression of, colon cancer. However, defects in the cellular mechanism(s) that integrate these pathways may have more profound affects on homeostasis and the tumorigenicity of a cell than defects in either individual pathway. We have previously established that butyrate, a natural constituent of the colonic contents, is a potent mediator of growth arrest and apoptosis in SW620 human colonic carcinoma cells. We also found that an intact deltapsimu (mitochondrial membrane potential) is required for the induction of apoptosis and, to our surprise, the initiation of growth arrest as well. Thus, we have hypothesized that the deltapsimu
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plays a critical role in integrating the signals that link cell cycle arrest and apoptotic cascades and, therefore, in determining the tumorigenic potential of a cell. To test this hypothesis, we have generated novel isogenic clones of SW620 cells that exhibit stable, significant alterations in basal deltapsimu. Consistent with a role in integrating proliferation and apoptosis, and in determining tumorigenicity, we found that the basal deltapsimu is significantly linked to the sensitivity of these cells to butyrate, and their ability to grow under adhesion-compromised conditions (preliminary data). Utilizing these unique cells, Aim 1 of this application dissects the impact of basal deltapsimu on butyrate sensitivity by defining the link between deltapsimu and the activity, subcellular distribution and interactions of p21WAF1/Cip1, TR3 and Smac, each of which have been implicated in integrating cell cycle arrest and apoptotic cascades. Aim 2 defines the impact of basal deltapsimu on the intracellular distribution of mitochondria and determines the relationship between deltapsimu- linked altered sensitivity to butyrate and mitochondrial distribution. Aim 3 dissects the affect of basal deltapsimu on tumorigenicity in vivo, and also recapitulates the deltapsim- linked altered sensitivity to butyrate by growing cells as xenografts in nude mice maintained on control or tributyrin diets. Finally, aim 4 couples our isogenic cell lines, the microarray facilities at Albert Einstein College of Medicine and the expertise of members of our group, to generate databases that profile the ground state of altered basal deltapsimu and the linked altered sensitivity to butyrate. These databases are integrated with those established by our group that profile numerous colonic epithelial cell maturation pathways to define the role of deltapsimu in maturation and provide critical insight into the molecular mechanisms associated with colon cancer risk and progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: COLON CANCER CHEMOPREVENTION BY URSODEOXYCHOLIC ACID Principal Investigator & Institution: Khare, Sharad; Medicine; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): My primary goal is to develop into an independent investigator in the field of colon-cancer chemoprevention. My long-term research objectives are to elucidate the mechanisms by which ursodeoxycholic acid exerts anticarcinogenic effects with respect to colon cancer. We have demonstrated that supplemental dietary cholic acid promoted the development of azoxymethane-induced rat colonic tumors. In contrast, dietary ursodeoxycholic acid (UDCA) inhibited tumorigenesis and suppressed cholic acid-induced tumor promotion. To examine the mechanisms by which UDCA causes anticarcinogenic effects, preliminary studies in the proposal demonstrated that UDCA inhibited Cox-2 gene expression at both the mRNA and protein levels and decreased Cox-2 immunostaining in stromal cells within the ACF. Furthermore, HCA-7 cells derived from a human colon cancer, demonstrated upregulation of Cox-2 in response to deoxycholic acid (DCA). DCA is the major metabolite of the primary bile acid cholic acid, and is a potent tumor promoting bile acid. In contrast, UDCA inhibited DCA-induced Cox-2 up-regulation in HCA-7 cells, further supporting our hypothesis that the chemopreventive actions of UDCA involve, at least in part, the ability of UDCA to inhibit Cox-2 expression in colon cancer. HCA-7 cells, therefore, manifest a similar response to UDCA with respect to Cox-2 inhibition as observed in the AOM model. These cells will, therefore, serve as an ideal in vitro model to dissect the molecular events involved in Cox-2 dysregulation in colonic
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carcinogenesis. They will also allow us to identify potential mechanisms by which UDCA acts to inhibit Cox-2 expression, and thereby suppress tumorigenesis. In our Specific aims we propose to elucidate the signal transduction pathways and regulatory components by which DCA up-regulates Cox-2, while UDCA suppresses this induction. The current project fits well into my long-term research objectives to evaluate the molecular targets of this chemopreventive bile acid. Our findings in this proposal will also likely identify potential blomarkers that we will validate in a future study involving human ACF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: COLON EXPERIMENT
CANCER
NETWORKS:
LINKING
MODELING
TO
Principal Investigator & Institution: Khalil, Iya G.; Gene Network Sciences, Inc. 2359 N Triphammer Rd Ithaca, NY 14850 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JAN-2003 Summary: (provided by applicant): Development of computational models of signal transduction pathways implicated in colon cancer is proposed. These models give insight into the pathway's dynamical behavior and elucidate their roles in activating known oncogenic target genes. The project will model the Ras Map Kinase signal transduction pathway, which plays a central role in the development of colon cancer. The methods utilized, which will be further developed, combine computational modeling with experiments so that unknown parameters in the model are constrained. The goal is to create accurate, predictive models by combining the forward modeling approach with experimental data. The computational and experimental processes developed can be applied to other pathways implicated in colon cancer. Accurate computational models of signaling pathways will bring rational, predictive science to the drug discovery process and lead to effective therapies for colon cancer. These simulations will help pharmaceutical and biotechnology companies prioritize drug targets, test the effects of lead compounds, and focus and direct laboratory efforts. Specific aims are (1) to develop a detailed mathematical and computational model of the Ras Map Kinase pathway; (2) to conduct experiments on pathway components to extract the data needed to constrain parameters in the model; (3) to use and devise optimization algorithms to constrain parameters in the model and (4) generate predictions from the model. PROPOSED COMMERCIAL APPLICATIONS: The research will provide an in silico simulation of the gene expression networks and signal transduction controlling the onset of colon cancer. New methods will be developed for incorporating data into the in silico platform generated by DNA microarrays, proteomics technologies, structural genomics, and protein-protein interaction studies to prioritize known drug targets. New mathematical analysis will make it possible to evaluate targets and lead compounds for drug development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: COLON CANCER PREVENTION PROGRAM PROJECT Principal Investigator & Institution: Alberts, David S.; Professor of Medicine and Pharmacology; Medicine; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2001; Project Start 30-SEP-1986; Project End 31-JUL-2005 Summary: Colorectal cancer is the third leading cause of cancer death in both males and females in the U.S. The overall, long-term goal of the Chemoprevention of Colon Cancer Program Project is to reduce the incidence, morbidity and mortality of colorectal cancer.
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To accomplish this goal, we seek to develop highly effective intervention strategies to prevent the recurrence of sporadic adenomatous polyps in subjects at increased risk for colon cancer and to define the fundamental epigenetic and genetic mechanisms of polyp genesis and recurrence. Our Program Project consists of three highly interactive scientific research components and will complete two large cancer control phase III studies in 2800 participants as follows: 1. A phase III randomized, placebo-controlled, double-blind cancer control study of the effect of ursodeoxycholic acid on recurrence of adenomatous polyps, with emphasis on proving the bile acid hypothesis that colon carcinogenesis is a progressive disorder of signal transduction involving the interaction of fat, bile acids and bacteria; 2. A phase II randomized, placebo-controlled, doubleblind study of factorial design of the effect of celecoxib, a COX-2 inhibitor, and selenium (formulated in backer's yeast), a nutritional supplement, and their combination on adenoma recurrence. These agents were selected because of their different mechanistic effects on the colon carcinogenesis signal transduction pathway, well-documented activity in animal models and safety profiles established in human studies; 3. An examination of CpG island methylator phenotype (CIMP) abnormalities, specific genetic alterations (APC, Ki-ras, p53), and biologic perturbations (PCNA, COX, apoptosis) in baseline adenomas and age-related DNA methylation and nuclear chromatin patterns in rectal mucosal biopsies, as predictors of adenomas recurrence; and 4. Project of factors enhancing susceptibility to colon carcinogenesis, including environmental/lifestyle characteristics and high prevalence polymorphisms in enzymes involved in folate metabolism and metabolism of heterocyclic amines, and their interaction with genetic and epigenetic mechanisms in relation to risk of adenoma recurrence. To accomplish our goals, we have brought together a group of outstanding cancer researchers who have developed a highly integrated, hypothesis-driven research proposal with a strong likelihood of success that was grafted so that will Projects and Core Services within six large universities depend scientifically and operationally on each other. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: COLON CANCER RISK COUNSELING FOR AT RISK RELATIVES Principal Investigator & Institution: Glanz, Karen; Professor; None; University of Hawaii at Manoa 2500 Campus Rd Honolulu, HI 96822 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 31-DEC-2003 Summary: Colorectal cancer is the second most common cause of cancer death in the United States. Early detection and intervention can significantly reduce morbidity and mortality from colorectal cancer (CRC). Individuals with a family history of CRC are at increased risk for the disease, and should have screening at younger ages and/or with increased frequency than the population at large. They also may benefit from personalized cancer risk counseling. This proposal is a competing continuation application that builds on an exploratory study of psychosocial and ethnocultural factors related to intentions to obtain genetic testing for heritable colon cancer, and a pilot study of genetic counseling for intermediate-risk CRC family members. The specific aims of the study are to: (1) evaluate the impact of a culturally sensitive program of Colon Cancer Risk Counseling (CCRC) on: a) adherence to guidelines for early detection for CRC, b) comprehension of personal colorectal cancer risk, and c) psychological adaptation to familial cancer, among individuals with family history of colorectal cancer (CRC); (2) evaluate the impact of CCRC on subgroups of persons at different levels of risk, various ages and educational levels, males vs. females, and persons of different ethnic groups; and (3) examine the extent to which risk comprehension and psychological adaptation mediate the impact of CCRC on
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adherence to screening. Subjects will be 700 siblings and children, aged 40 and over, who have a positive history of colorectal cancer (CRC) in one first-degree relative. Subjects will be randomly assigned to receive either: (1) Colon Cancer Risk Counselling or (2) a General Health Counseling control. The theoretical foundation of the intervention and evaluation uses constructs from the Precaution Adoption Model and the Transactional Model of Stress and Coping. Both models concern how individuals perceive threatening situations, and which factors determine whether they take protective action or engage in adaptive coping behaviors. The CCRC intervention will be an individual face-to-face counseling session that emphasizes communication of individualized CRC risk, addresses perceived benefits of and barriers to early detection, and assists participants in developing action plans for appropriate screening; plus 2 follow-up phone calls. The General Health Counseling (GHC) control will address health promotion related to diet, exercise, tobacco use, and screening. Surveys at baseline, 4 months and one year post-intervention will assess the impact of the interventions on colorectal screening adherence, risk comprehension, and psychological adaptation. If effective, the CCRC interventions for these persons at increased risk for colorectal cancer, for whom predictive genetic testing and genetic counseling are usually not available, can be provided in primary care settings or family cancer risk programs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: FACTORS
COLON CANCER
RISK:
IGF POLYMORPHISMS/LIFESTYLE
Principal Investigator & Institution: Newcomb, Polly A.; Member and Acting Head; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, WA 98109 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: Recent epidemiologic studies have shown that elevated levels of circulating insulin-like growth factor 1 (IGF-1) and decreased levels of circulating insulin-like growth factor binding protein 3 (IGFBP-3) are associated with increased risk of colorectal cancer. Many of the genes in the IGF axis are polymorphic, and studying this genetic variation as potential markers of susceptibility for colon cancer may have important implications for cancer prevention. As an adjunct to an existing populationbased case-control study we propose to 1) evaluate the association between polymorphisms in IGF-1 and IGFBP-3 genes and colorectal cancer risk, and 2) to assess whether the associations between various lifestyle risk factors (such as hormone replacement therapy, physical activity, and obesity) and colorectal cancer are modified by the presence of these polymorphisms. Because the importance of polymorphisms in the IGF-1 and particularly the IGFBP-3 genes are not well understood, we additionally propose to determine whether these polymorphisms are associated with differential levels of circulating plasma IGF-1 and IGFBP-3 among cancer-free community controls. 400 men and women aged 20-74 years with a new diagnosis of colorectal cancer identified through the Puget Sound SEER registry and 400 community controls will be included in this proposed analysis. A structured telephone interview will assess HRT use, body size, physical activity, history, reproductive history, family history of cancer and demographic information. DNA from blood and buccal samples will be used to determine IGF polymorphism genotype. Plasma samples will e analyzed for circulating IGF-1 and IGFBP-3 levels. As an adjunct to an existing study, this is an efficient, valid cost-effective approach to the investigation of the association between polymorphisms and cancer risk.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: COLON CANCER SCREENING MULTIMEDIA EDUCATIONAL WEBSITE Principal Investigator & Institution: Mcgee, James B.; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 23-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant) This research will plan and develop a World Wide Web educational site for patients and physicians to calculate an individual's risk for colon cancer and determine his or her personalized screening, surveillance, and prevention program. In addition, the site will provide users with multimedia, interactive tools to learn about his or her individual screening procedures. The educational design will include the use of virtual patients and an online virtual physician to teach patients the significance of colon cancer screening and what to expect when they receive screening examinations. A related site will provide primary care physicians with an interactive tool to assess a patient's risk for cancer and help to recommend the optimal screening modalities. The expected outcome of this research will be high-quality education on cancer screening and prevention that results in a greater percentage of atrisk individuals receiving appropriate screening and a decrease in the incidence, morbidity and mortality from colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COLON CANCER SPECIFIC RADIODIAGNOSTIC/THERAPEUTIC AGENTS Principal Investigator & Institution: Volkert, Wynn A.; Curator's Professor of Radiology; Radiology; University of Missouri Columbia 310 Jesse Hall Columbia, MO 65211 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Description (provided by applicant): This proposal describes the design and evaluation of new conjugates of synthetic human E. coli ST (STh) peptides that form high specific activity site-directed radiopharmaccuticals for selective in vivo targeting of colorectal neoplasias that express guanylin/guanylate cyclase-C (GC-C) receptors. Diagnostic or therapeutic radiopharmacouticals that result from this work will be labeled with 11In, 90Y, 149Pm or 177Lu, radionuclides that are available as no-carrier-added (NCA) reagents that have half-lives compatible for preparing radiometallated receptor-avid peptide conjugates. The specific objectives of this research are to: 1) synthesize new DOTA-X-Phe19-STh analogues that exhibit high specific binding affinities with human colon cancer cells expressing GC-C receptors; 2) use normal and tumor-bearing animal models to identify radiolabeled peptides that exhibit optimal in vivo pharmacokinetics and tumor uptake and residualization properties; 3) evaluate the diagnostic or therapeutic efficacy of the most promising DOTA-X-Phe19-STh constructs when labeled with. 111In or with 90Y, 149Pm and 177Lu for controlling or ablating human LS-180/T84 colon cancer cell derived tumors in SCID mice. The new DOTA-X-Phe19-STh (X=spacer group) and the corresponding 111In, 90Y, 149Pm and 177Lu labeled conjugates will be synthesized, purified and characterized at both macroscopic and tracer levels. The experimental approaches used in the proposed research are designed to characterize structures that maximize cancer cell uptake and GC-C receptor-mediated intracellular residualization. The ability to synthesize predetermined tether (X) sequences linking DOTA and Phe19-STh also enables identification of conjugate constructs that minimize residualization of activity in critical non-target organs or
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tissues. The results of these studies should provide DOTA-X-Phe19-STh analogues that, when labeled with 111In+3, 90Y+3, 149Pm+3, 177Lu+3 and potentially other radiometals, could be developed (via future FDA approved clinical trials) into effective radiopharmaccuticals for monitoring or treatment of patients with colonic neoplasias overexpressing GC-C receptors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: COLON CANCER SURVIVORS--MEDICATIONS & RISK OF RECURRENCE Principal Investigator & Institution: Johnson, Christine C.; Ch Epidemiologist; Josephine Ford Cancer Center; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, MI 48202 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the Applicant's Abstract): Colorectal cancer will be diagnosed in over 129,000 Americans in 1999. To combat this disease, new avenues to decrease the risk of colorectal cancer, such as chemoprevention, are being explored by researchers. Non-steroidal anti-inflammatory drugs (NSAIDs) and hormone replacement therapy (HRT) have been shown to decrease incident colon cancer. Little is known of their effect on persons with a history of colon cancer which, fortunately, is a continually expanding population as survival has been significantly improving over the last twenty years. The objective of this epidemiologic study is to determine whether NSAIDs or HRT is associated with recurrence or survival among individuals diagnosed with colorectal cancer. The proposed research will establish a cohort of colorectal cancer patients treated with curative intent and create a comprehensive longitudinal database, including data on the ascertainment of subsequent adenomatous polyps, colorectal cancer and survival. The specific aims are: (1) to determine whether NSAID use deceases the risk of recurrence of colorectal cancer; (2) to determine whether HRT use deceases the risk of recurrence of colorectal cancer; (3) to determine whether NSAID use affects short-term survival; and (4) to determine whether HRT use affects short-term survival. The cohort will be established from colorectal cancer patients enrolled in two managed care organizations, Health Alliance Plan (Detroit, MI) and HealthPartners (Minneapolis, MN). Cohort subjects will be followed for at least five years for new evidence of disease, recurrence and survival outcome. Using automated pharmacy data, the timing of use and exposure to NSAIDs and HRT will be analyzed among cancer survivors, along with potentially confounding variables, in relation to these outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COLONIC CELLS:NON-INVASIVE ISOLATION TECHNOLOGY Principal Investigator & Institution: Nair, Padmanabhan P.; Noninvasive Technologies, Llc 4520 Hemlock Cone Way Ellicott City, MD 21042 Timing: Fiscal Year 2002; Project Start 03-JUN-1999; Project End 31-JUL-2004 Summary: (Applicant's abstract): Colorectal carcinoma is the most common gastrointestinal malignancy affecting about 160,000 new cases per year in the United States. Survival rates are closely correlated with the stage of cancer at the time of diagnosis. This Phase II (revised) proposal is based on the fact that it is possible to recover colonic cells from human stool and examine them for biomarkers associated with malignant transformation. Our objective is to develop a noninvasive screening test for colon cancer by demonstrating the expression of tumor associated biomarkers on exfoliated colonocytes isolated from stools of patients with colon cancer. This is a cross-
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sectional observational study of patients undergoing diagnostic colonoscopy at two medical centers: Sinai Hospital in Baltimore and the Walter Reed Army Medical Center in Washington, D.C. The outcome measures are PCR amplicons of CD 44 splice variants and tumor specific variants of carcinoembryonic antigen (CEA). In addition, cell surface carbohydrate motifs linked to tumorigenesis will be examined by flow cytometry using fluorescently labeled plant lectins that are now to be specific ligands. From previous studies we expect to show a high degree of sensitivity and specificity for detection of colon cancer and its precursor polyps using a panel of these biomarkers. As a reference marker Cytokeratin 19 will be amplified, semiquantitatively, by PCR using cDNA generated from mRNA extracted from the cells. Our objective is to develop a standardized kit for the detection of colon cancer, non-invasively, as a cost-effective screening tool. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: COLONIC CYTOKINETICS AND CELL SIGNALING--DIETARY EFFECT Principal Investigator & Institution: Chapkin, Robert S.; Professor & University Faculty Fellow; Animal Sciences; Texas A&M University System College Station, TX 778433578 Timing: Fiscal Year 2001; Project Start 23-DEC-1994; Project End 30-APR-2003 Summary: Among dietary factors, there is strong epidemiological, clinical and experimental data indicating a protective effect on n-3 polyunsaturated fatty acids (n-3 PUFAs; eicosapentaenoic acid, 20:5n- 3 and docosahexaenoic acid, 22:n-3) on colon cancer. We have recently demonstrated that dietary n-3 PUFAs confer protection against experimental carcinogenesis, i.e., a reduction in tumor incidence, in part by enhancing the deletion of cells through activation of apoptosis, which may reduce the accumulation of genetic errors. These data support our postulate that dietary n-3 PUFAs act as anticarcinogens by facilitating the apoptotic removal of carcinogen adducted cells. In order to further elucidate the mechanism(s) by which n-3 PUFAs-induce apoptosis. We will utilize the highly relevant rat model of colon carcinogenesis to determine whether n-3 PUFAs modulate DNA adduct formation, removal (DNA repair) and/or deletion (apoptosis) during the initial stages of malignant transformation. We have also recently show that n-3 PUFAs prevent the carcinogen-induced chronic down-regulation of colonic protein kinase C (PKC) delta (novel), zeta (atypical), and the selective upregulation of PKC betaII (classical). This is significant because the maintenance of crypt PKC levels may sustain the homeostatic balance between cell proliferation and apoptosis. Therefore, we have hypothesized that n-3 PUFAs reduce colon cancer incidence in part by blocking the effects of carcinogen on colonic PKC isozyme-related signal transduction. To further determine the significance of n-3 PUFA-induced changes in colonic PKC expression, we will elucidate the role of specific PKC isozymes in colon tumor development by using a targeted pharmacological inhibitor in vivo in combination with overepression and antisense strategies in vitro. Elucidation of the mechanism(s) by which dietary n-3 PUFAs reduce colon cancer incidence will lead to the establishment of dietary guidelines designed to reduce colon cancer morbidity and mortality. This experimental approach is particularly relevant because despite advancement in the treatment of colon cancer, the 5 year mortality rate has not appreciable improved over the past 4 decades. Therefore, chemopreventive dietary strategies must be developed in order to decrease the risk of colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COLORECTAL CANCER CARE VARIATION IN VULNERABLE ELDERLY Principal Investigator & Institution: Baldwin, Laura-Mae; Associate Professor; Family Medicine; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 04-JUN-2001; Project End 31-JAN-2004 Summary: Specific Aims: This study's long-term goal is to improve colorectal cancer care for the elderly who have a high incidence of this highly treatable and potentially curable disease. In 1990, a National Institutes of Health Consensus Panel recommended adjuvant therapies for colorectal cancer patients with stage III colon and stage II and III rectal cancer. The degree to which the elderly, especially traditionally vulnerable groups, are receiving these recommended treatments is unclear. This study will (1) compare the receipt of recommended colorectal cancer treatments between AfricanAmerican and Hispanic versus white elderly, and rural versus urban elderly; (2) compare diffusion of these treatments from 1992-1996 between our study groups; (3) identify the physician, patient, hospital, and environmental factors that predict differences found in treatment or diffusion; (4) measure treatment cost differences between our study groups, and the cost implications to the Medicare program of providing recommended treatments to all beneficiaries with colorectal cancer; and (5) evaluate several methodologies for cancer research using administrative databases, including different measures of comorbidity and costs. Research Design and Methods: This study will use the linked SEER-Medicare claims database in a retrospective cohort design to examine differences in receipt, diffusion, and cost of recommended colorectal cancer treatments between more and less vulnerable elderly populations. Using stage III colon and stage II and III rectal cancer cases identified in SEER between 1992 and 1996, we will identify different patterns of treatment and alternative measures of the costs for colorectal cancer care with Medicare claims data. Annual study cohorts will be tracked in a comprehensive database using 1991-1998 linked SEER-Medicare, AMA Masterfile, AHA, and Area Resource File data. Physician, hospital, and patient characteristics (including cancer stage and comorbidity) will be linked to the location, size, and socioeconomic profile of places of residence, travel distances to different treatment sites and cancer specialists, service utilization, and allowed charges. In the second phase of the study, we will use multivariate analysis to identify the degree to which physician, patient, hospital and environmental factors predict systematic differences in treatment patterns between our study populations. The cost analysis will include an estimate of the resources required to bring all patients up to the recommended standard of care. Alternate methods of defining comorbidity and costs will be used to evaluate their utility in cancer research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COMBINATION GENE THERAPY FOR METASTATIC COLON CANCER Principal Investigator & Institution: Chen, Shu-Hsia; Assistant Professor; Inst/Gene Therapy & Mol Med; Mount Sinai School of Medicine of Nyu of New York University New York, NY 10029 Timing: Fiscal Year 2002; Project Start 01-APR-1996; Project End 30-APR-2006 Summary: (provided by applicant): In the U.S., metastatic colon carcinoma is second only to lung cancer as the cause of death from malignancy in the United States, accounting for 60,000 fatalities a year. 80 percent of the patients who died of colon cancer have metastases in the liver, and half of them have only liver metastases at the
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time of death. Current treatments include surgery and chemotherapy, with a mean survival time of only 37 months. Using an orthotopic murine model for pre-established hepatic colon cancer, we have shown that intratumoral injection of an adenoviral vector expressing murine interleukin-12 (Adv.mIL-12) led to tumor regression and prolonged survival of treated mice. However, the anti-tumor immunity induced by this type of gene therapy was mediated primarily by natural killer (NK) cell. In order to also induce a tumor specific T cell response as well, we co-administered an agonistic monoclonal antibody against murine 4-1BB, a co-stimulatory molecule on activated T cells, to induce CD8+ T cell activation and proliferation. The combination treatment resulted in the induction of a strong anti-tumoral immunity and 80 percent long-term survival in the tumor-bearing animals (5x5 m2), even with an eighteen-fold reduction of the Adv.RSVmIL-12 dose. However, the combination treatment can only induce an NK and CD8+ T cells mediated anti-tumor responses and is less effective for large tumors (lOx10 mm2). In order to achieve persistent anti-tumor immunity and improve therapeutic effect when treating large tumors, the activation of CD4+ T helper cells will be incorporated into the combination therapy via agonistic antibodies against the co-stimulatory molecule OX40, an activation molecule on activated CD4 T helper cells, or CD40, an activation molecule on activated antigen presenting cells (APC). Three specific aims will be pursued: 1) To determine whether intra-tumoral IL-12 gene delivery in conjunction with agonistic antibodies against 4-1BB plus OX40 and/or CD40 can achieve better therapeutic effect for large tumors and generate persistent anti-tumor immune responses to prevent residual and metastatic tumors. 2) To examine the role of CD4 T cells in the accentuated development of tumor specific CD8 memory T cells in combination treated animals. 3) To investigate whether the CD4O and OX 40 activated immune cells can overcome the immune tolerance in mice with a large tumor burden. Successful completion of these studies will result in a better understanding of the interaction of APC, CD4, and CD8 cells in the establishment of anti-tumor memory CD8 T cells and immune suppression/tolerance mediated by a large tumor burden. These therapeutic strategies will be utilized as the scientific foundation for active immune modulation of patients with metastatic colorectal cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: COMBINED CHEMOPREVENTION IN BETA-CATENIN MUTANT MICE Principal Investigator & Institution: Orner, Gayle A.; None; Oregon State University Corvallis, OR 973391086 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Colorectal cancer is the second leading cause of cancer deaths in the United States. According to the American Cancer Society, more than 130,000 Americans will be diagnosed with cancer of the colon or rectum this year. Fortunately researchers are making extraordinary progress in the development and/or identification of agents that may delay or prevent colorectal cancer. These include pharmaceuticals such as the non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs are effective at preventing polyp formation in familial adenomatous polyposis (FAP) patients having a genetic predisposition to cancer. Epidemiological evidence suggests that long-term NSAID use is associated with a decreased risk of colon cancer in nonfamilial colon cancer as well. However, NSAIDs can produce serious side effects, including gastrointestinal bleeding and even death. One strategy to minimize toxicity of NSAIDs is to use very low doses in combination with other agents having complementary modes of action. Tea prevents intestinal and/or colorectal cancer in a
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variety of animal models. A combination of tea plus the NSAID sulindac was recently shown to be highly effective at preventing the formation of tumors in Apc[min] mice. These mice have a mutation in Apc (same gene altered in FAP) and, like humans with FAP, are genetically predisposed to develop large numbers of intestinal adenomas at an early age. This suggests that a combination of tea plus sulindac may be of benefit in treating humans with FAP. However, the majority of human colon cancers are not hereditary; instead their cause is unknown, but may be due to interaction of environmental and genetic factors. The A33[delta-N-beta-cat] mouse is an innovative new animal model that may be particularly appropriate as a mimic for non-familial colorectal cancer. A33[delta-N-beta-cat] mice express an oncogenic form of beta-catenin in their intestines. The A33[delta-N-beta-cat] mice do not develop multiple intestinal tumors at an early age like Apc[min] mice, but are highly susceptible to chemically induced colon cancer. The proposed studies are the first chemoprevention studies to be conducted in A33[delta-N-beta-cat] mice. These studies will examine the combined benefits of tea plus low-dose sulindac as preventive agents towards colon cancer. This research will provide valuable information on how dietary factors and pharmaceuticals interact in the prevention of intestinal cancer, and may also expedite future cancer prevention research through further validation of the A33[delta-N-beta-cat] mouse model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: COMPUTERIZED COLONOGRAPHY
DETECTION
OF
POLYPS
IN
CT
Principal Investigator & Institution: Yoshida, Hiroyuki; Radiology; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2003; Project Start 03-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Colon cancer, the second leading cause of cancer deaths for men and women in the United States, can be prevented if precursor colonic polyps are detected and removed. The long-term goal of the proposed project is to advance the early detection of colon cancer. Computed tomographic colonography (CTC) has been proposed as a promising technique for colon cancer screening, but for CTC to be a practical screening tool, many images must be interpreted rapidly and accurately. To this end, the short-term goal of the project is to develop a highperformance computer-aided diagnosis (CAD) scheme for the automated detection of polyps in CTC to assist radiologists in detecting polyps quickly and accurately, by providing them with a "second opinion" regarding the locations of suspicious polyps. We hypothesize that a CAD scheme can significantly reduce radiologists' interpretation time and improve their performance in detecting colonic polyps in CTC. To explore this hypothesis, we propose the following specific aims: Specific Aim 1. Establish a large CTC database of polyps to develop and evaluate a CAD scheme: (1) Collect new CTC cases of polyps retrospectively and prospectively. Specific Aim 2. Develop methods for the detection of polyp candidates: (1) Generate isotropic volumetric data from axial CT images; (2) Develop methods for automated extraction of the colon based on apriori knowledge of the abdominal anatomy; (3) Develop methods for extraction of polyp candidates based on geometric features. Specific Aim 3. Develop methods for the reduction of false positives: (1) Develop methods of clustering of polyp candidates to merge polyp candidates and to remove false positives due to noise; (2) Develop methods based on 3-dimensional volumetric features that differentiate polyps from false positives due to normal anatomic structures; (3) Use diseriminant analysis, artificial neural networks, and genetic algorithms to merge volumetric features for the reduction of false
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positives. Specific Aim 4. Evaluate the performance and benefit of the overall CAD scheme: (1) Evaluate the performance of the CAD scheme in the detection of polyps in CTC. (2) Evaluate the benefit of the CAD scheme in reducing radiologists' interpretation time and improving diagnostic performance in the detection of polyps by means of an observer study. Successful development of such a CAD scheme will advance the clinical implementation of CT-based colon cancer screening, promote early diagnosis of colon cancer, and ultimately reduce mortality due to colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: CONFERENCE--IMPACT OF THE ENVIRONMENT ON COLON CANCER Principal Investigator & Institution: Veigl, Martina L.; Environmental Mutagen Society 1767 Business Center Dr, Ste 302 Reston, VA 20190 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2004 Summary: (provided by applicant): This application is a request for funds to partially support an international scientific conference organized by the Environmental Mutagen Society entitled "Impact of the Environment on Colon Cancer". The conference will be held from May 14 - May 16, 2003 in the Fontainebleau Hilton Hotel in Miami, Florida. This specialty meeting will bring together laboratory and clinical researchers from a variety of disciplines to evaluate the evidence for a relationship between exposure to environmental mutagens/carcinogens and colon cancer development. Our colon cancer meeting represents the second of a series of special conferences be organized by the EMS to explore the role of environmental mutagens/carcinogens in specific diseases. Through these specialty meetings, the EMS wants to use its organizational structure and membership base to (1) bring attention to the potential role that environmental mutagens/carcinogens play in the etiology of specific diseases, (2) bring together scientists from a wide variety of disciplines [including chemistry, molecular & cellular biology, genetics, medicine and epidemiology] to focus on such problems, and (3) emphasize the critical role that environmental science plays in understanding human disease and improving human health. The conference schedule includes 6 symposia and 2 Workshops/Discussion sessions. We anticipate an attendance of 150-300 people for this 2 1/2-day Specialty Meeting. Opportunities for poster presentations will be available for participants and if sufficient support can be obtained we will offer Travel Awards to graduate and medical students and post-doctoral fellows. In order to have a permanent record of the proceedings, we have obtained initial approval from the Editorin-Chief of the official journal of the EMS, Environmental and Molecular Mutagenesis, to publish manuscripts from the invited speakers in a Special Issue of the journal. Finally, we are applying for continuing Medical Education (CME) accreditation so that physicians and other health-care professionals can obtain CME credit for attending this conference. External support is vital to the success of this conference and we are currently soliciting funds from government agencies as well as private foundations and industry. This support will be used to defray part of the cost for (1) travel for invited speakers, (2) advertisement and promotion of the conference, and (3) student travel awards. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--CELL AND TISSUE PATHOLOGY FACILITY Principal Investigator & Institution: Bernstein, Harris; University of Arizona P O Box 3308 Tucson, AZ 857223308
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Timing: Fiscal Year 2001; Project Start 01-JUL-1997; Project End 31-DEC-2005 Summary: APPLICANT'S Core A will provide endpoint analyses for experiments involving apoptosis in both cell culture systems and in animal and human tissues. Apoptosis analyses for cell culture will include bright field examination (LM) using Romanowsky-type dyes or polychrome stains and transmission electron microscopy (TEM). Apoptosis will be quantitated in animal and human colonic specimens using light microscopy. The core will be responsible for maintaining and testing flat mucosa from colon resections and from colonoscopies (from cancer patients, adenoma patients, and "normal" patients). Tests would include measurements of apoptosis and specific proteins of interest to the project directors. We will use fluorochrome tags on secondary antibodies to detect specific proteins in conjunction with Leica Laser Scanning Confocal Microscopy (LSCM), or produce permanent slides using immunohistochemical procedures. By these approaches we will identify and quantify gene products of significance to the three projects, including proteins which may prove valuable as biomarkers of colon cancer risk (e.g. Hsp70, Cox-2, Gadd153, and others. Quality control studies will be performed to measure expression of potential biomarkers in each of the different regions of the colon of normal individuals as a basis for identifying abnormal expression in high risk individuals. The core will also measure expression of potential biomarkers in the normal appearing mucosa of cancer patients at various distances from the cancer. The core will establish, maintain, subclone and test apoptosis resistant colonic epithelial cell lines for altered gene expression. Cellular effects of chemopreventive agents, of other drugs and of transfections will be evaluated by microscopic methods applicable to the particular experimental situation. Procedures to be made available are ultrastructural cytochemistry (including cryosectioning), fluorescent apoptosis/necrosis assay, bright-field examination of cytospin preparations, semi-thin plastic sectioning, and paraffin embedding. The core will also assist in developing special microscopic procedures to answer specific questions that emerge as experimental data are obtained and analyzed. Two experienced research specialists will be available in the core to provide this assistance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: CORE--GHC POPULATION AND SURVEILLANCE Principal Investigator & Institution: Chu, Susan; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, WA 98109 Timing: Fiscal Year 2001 Summary: The Overall goal of this Core is to support individual projects and overall objectives by identifying and recruiting patients for participation in Program Project Studies, by collecting gastrointestinal cancer tissues from cases that arise in a population of approximately 400,000 enrollees, and by enhancing the ability of Program Project investigators to conduct longitudinal studies in colon and pancreas cancer. Through the Center for Health Studies, the GHC Population Core will facilitate access to a health care delivery system that has distinct advantages as a setting for translational research that include a large defined patient population and a rich array of information systems; established programs in cancer screening with linkage to risk factors and pathologic outcomes; and experience in the design, conduct, and analysis of intervention and observational studies of cancer prevention, control and treatment. The specific aims of the GHC Population Core are: 1) To identify and collect specimens from patients with chronic pancreatitis, pancreatic cancer, and colon cancer for proposed projects 1 and 4; 2) To recruit patients undergoing colonoscopy and collect risk factor data, fecal and blood samples, and biopsy results, and tissue specimens for longitudinal studies of
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colon cancer risk and development; and 4) To establish a surveillance system to monitor changes in gastrointestinal cancer incidence, morbidity, and mortality in our defined population. The GHC Population Core will build and maintain a retrospective registry with linked pathology results of more than 9800 patients who underwent colonoscopy between 1991 and 1996 and will add risk factor data for the anticipated 4800 patients who will be colonoscopied during the project period. Group Health Cooperative (GHC) is a staff-model managed care organization that serves over 400,000 enrollees in the western Washington Puget Sound region. The GHC Population Core will operate within the GHC Center for Health Studies, a research organization dedicated to the conduct of studies that contribute to scientific knowledge in the public domain and to the quality of health care at GHC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: COVALENT MODIFACTION OF PPAR GAMMA IN COLON CANCER Principal Investigator & Institution: Girnun, Geoffrey D.; Dana-Farber Cancer Institute 44 Binney St Boston, MA 02115 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): The nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma) has been shown to play a crucial role in adipogenesis. In recent years, there has been an interest in the role of PPARgamma in cancer. Colon cancer represents one of the leading causes of death in the United States. PPARgamma is expressed at high levels in normal and malignant colonic tissue. Therefore, we have been interested in understanding the role of this receptor in the colon.. Interestingly, the role of PPARgamma in the colon has been controversial with studies indicating both anti- and pro-cancer effects. Recently we have demonstrated in mice heterozygous at the PPAR? locus, that PPARgamma is playing a tumor suppressor role in the colon. Since PPARgamma is a tumor suppressor, the presence of PPARgamma in colonic tumors and cells suggests a disconnect between PPARgamma function and expression. Several studies have shown that PPARgamma is inactivated following MAPKinase-mediated phosphorylation of a conserved serine residue. Several pathways that lead to activation of the MAPKinase pathway have been shown have increased activity in colon cancer. This suggests that one possible reason for the presence of PPARgamma in colon cancer, and discrepancy in response to PPARgamma ligands could be due to PPARgamma phosphorylation. This proposal describes several experiments to critically evaluate the role of PPARgamma phosphorylation in colon cancer. Using pharmacological and eventually genetic approaches we will examine the role phosphorylation of PPARgamma on colon cancer cell growth and gene expression both in vitro and in vivo. A crucial aspect of these studies will be to determine possible mechanisms for the loss of PPARgamma activity due to phosphorylation. This will entail examining the ability of cofactors, both known and potentially novel, to interact in a phospho-dependent manner. Understanding the mechanism of phosphorylation-mediated inactivation of PPARgamma will not only provide insight in to the role of PPARgamma phosphorylation in colon cancer, but also other diseases where PPARgamma has been shown to play a role such as atherosclerosis and diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COX-2 PREVENTION
INHIBITOR
AND
N-3PUFA
IN
COLON
CANCER
Principal Investigator & Institution: Reddy, Bandaru S.; Associate Director of Research; Institute for Cancer Prevention 1 Dana Rd Valhalla, NY 10595 Timing: Fiscal Year 2003; Project Start 30-SEP-1993; Project End 30-JUN-2008 Summary: (provided by applicant): The long-term objective of our research is to identify innovative strategies for colon cancer prevention and to apply the knowledge from preclinical efficacy studies to use with individuals at high-risk for colon cancer as a means of prevention. Current evidence suggests that a diet rich in n-3 polyunsaturated fatty acids (n-3 PUFAs) and cyclooxygenase (COX)-2 inhibitors, such as celecoxib suppress azoxymethane (AOM)-induced colon carcinogenesis in F344 rats. Although colon tumor inhibition by COX-2 inhibitors is much more effective than traditional NSAIDs, high doses of COX-2 inhibitors have caused some side effects in humans. The preclinical experiments proposed in this application will provide compelling evidence that the aggregate action of n-3 PUFA-rich diet in combination with a COX-2 inhibitor, celecoxib would be significant, while side effects induced by the COX-2 inhibitor would be minimized. The proposed studies will evaluate two hypothesis: a) There is synergism in the mechanisms of action of COX-2 inhibitors and n-3 PUFAs, the former inhibiting carcinogenesis through modulation of generation of eicosanoids, angiogenesis and apoptosis while the latter suppressing colon carcinogenesis through NO pathways, cell differentiation and apoptosis, b) the combination of a diet rich in n-3 PUFAs with a COX-2 inhibitor will increase the efficacy by modulating synergistically the above molecular parameters. The specific aims are: 1) Determine the efficacy of a low dose of celecoxib administered in n-3 PUFA rich diet as compared when a high dose of this agent administered in a high-fat, Western style diet containing mixed lipids in AOMinduced colon carcinogenesis in F344 rats. 2) Determine the combined effects of celecoxib administered in n-3 PUFA-rich diet on colon cancer-related genes in colonic mucosa and tumors of rats. We will focus on apoptotic genes, Bcl-2, NF?B and on the eicosanoid- and NO-pathways including COX-2, LOX, and iNOS and their interactions with other functional groups of genes in colon carcinogenesis using DNA microarrays, RT-PCR and Western Blot analysis. Clear delineation of the synergistic effects in preclinical models will allow the rational design of human clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: CPT11 ACTIVATION BY CARBOXYLESTERASES IN COLON CANCER Principal Investigator & Institution: Bosron, William F.; Professor; Biochem and Molecular Biology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, IN 462025167 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2004 Summary: This is a R21 developmental grant application in response to NCI PA- 01-010, "Exploratory studies in cancer detection, prognosis and prediction." The overall goal is to produce a CPT-11 (Irinotecan) carboxylesterase assay that could be used to predict treatment outcome and/or toxicity for patients on CPT-11 therapy for colorectal cancer. CPT-11 is a semi-synthetic pro-drug that is activated by hydrolysis in vivo to SN-38. SN38 is a potent inhibitor of topoisomerase I and therapy inhibits cell growth. Another important metabolite called APC is also hydrolyzed to SN-38. The specific carboxylesterases responsible for the hydrolytic activation of CPT-11 and APC to SN-38 are not known. Two human carboxylesterases, hCE-1 and hCE-2 is highly expressed in
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intestine, which may be related to the major toxic complication of CPT- 11 therapy, diarrhea. Our hypothesis is that the tissue and cell-specific expression of CPT-1 and APC carboxylesterases may be an important determinant of the therapeutic outcome and toxicity associated with the APC carboxylesterases. Analysis of carboxylesteraselike genes in GenBank and preliminary observations in tumor cell lines suggest that there may be other carboxylesterases that could catalyze the hydrolysis of CPT-11 and APC. Proteomics and PCR methodologies will be used to screen for carboxylesterases and kinetic analysis with CPT-11 and APC as substrates will be performed with isolated or expressed enzymes. The second scientific aim of the grant is to develop and validate assays employing activity assays, gel electrophoresis or PCR methodologies for analysis of CPT-11 carboxylesterase expression in tumor and normal colon tissue from patients treated with CPT-11. A pilot study will be performed with tumor and normal tissue collected from patients at the Indiana University Cancer Center who presented with metastatic disease at diagnosis. After surgery the patients will be treated with 5fluorouracil, Leucovorin and CPT-11. The response to CPT-11 therapy and associated toxicity will be compared to carboxylesterase expression in tumor and normal colon tissue. If there is a positive correlation, a future multi-institutional study will be proposed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: CYCLOOXYGENASE AND TUMORIGENESIS Principal Investigator & Institution: Hwang, Daniel H.; Professor; None; Lsu Pennington Biomedical Research Ctr 6400 Perkins Rd Baton Rouge, LA 70808 Timing: Fiscal Year 2001; Project Start 10-SEP-1999; Project End 30-JUN-2002 Summary: Epidemiological studies have demonstrated that nonsteroidal antiinflammatory drugs (NSAIDs) can reduce the incidence of colon cancer. Since the well-documented pharmacological action of aspirin and other NSAIDs is inhibition of cyclooxygenase [COX, the rate limiting enzyme in prostaglandin (PG) biosynthesis], it can be inferred that the beneficial effect of NSAIDs may be mediated through the inhibition of PG biosynthesis. However, several lines of experimental observations imply that the beneficial effects of NSAIDs may be mediated through both COXdependent and COX-independent pathways. Thus, Specific Aims are: 1) To determine whether the overexpression of COX in colon cancer cell lines or normal intestinal epithelial cells by transfecting with constitutively expressed COX-1 or inducible COX-2 cDNA, results in changes in tumorigenic phenotypes, and whether inhibiting COX by NSAIDs abrogates the changes in vitro (cells in culture) and in vivo (growth of transplanted tumors to athymic nude mice). Results from these studies will establish or negate a direct link of COX to tumor cell growth. 2) To determine whether cyclooxygenase-independent effects of NSAIDs are mediated through mitogen-activated protein kinase (MAPK), NFkappaB or peroxisome proliferator-activated receptor (PPAR) signaling pathways. Recent evidence suggests that NSAIDs modulate MAPK, NFkappaB and PPAR signaling pathways. Thus, these studies are aimed to identify COX-independent signaling pathways through which NSAIDs suppress tumorigenesis. 3) To identify differentially expresssed genes in the colon cancer line and normal intestinal epithelial cells overexpressing COX-2 by subtractive hybridization and Serial Analysis of Gene Expression methods. Identifying up-or-down-regulated genes caused by the overexpression of COX-2 or NSAID treatment in the cancer cells will provide a clue as to how increased prostaglandin production can lead to changes in tumorigenic phenotypes, or a clue to identifying the cellular targets (other than COX) of the NSAID actions. 4) To determine whether prostaglandin receptors that activate adenylate cyclase
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are differentially expressed in the colon cancer cells as compared with normal cells and to identify downstream signaling pathways of prostaglandin E receptor (Ep2). Understanding the roles of prostaglandins and their signaling pathways in cancer cells could help explore new treatments and/or preventive strategies for colon cancer and perhaps other cancers using pharmacological agents and/or dietary means that modulate prostaglandin biosynthesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: CYTOKINE GENE TRANSFER FOR METASTATIC COLORECTAL CANCER Principal Investigator & Institution: Luxembourg, Alain T.; Senior Research Scientist; Ichor Medical Systems 6310 Nancy Ridge Dr, Ste 107 San Diego, CA 92121 Timing: Fiscal Year 2003; Project Start 10-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Metastatic colon cancer represents a significant healthcare problem in the U.S., with 50,000 new cases diagnosed annually and median survival at less than 2 years. The identification of tumor-associated antigens in colon cancer provides the basis to evaluate immunological treatment strategies. Despite showing promise in some cancers, immunotherapy using systemic cytokine administration has largely disappointed due to low response rates and high toxicity. Intratumoral gene transfer has been proposed as an alternative means of administration to improve the therapeutic and toxicologic profile of these molecules. Unfortunately, clinical implementation is hampered by the lack of clinically viable gene delivery vectors. Recent studies of in vivo electroporation demonstrate dramatic improvement in intratumoral delivery of therapeutic agents. Ichor has developed proprietary electroporation technology enabling safe and effective application of the procedure. Initial preclinical work suggests that Ichor's system is a promising means for intratumoral cytokine gene delivery. Under FLAIR Phase-l, Ichor will evaluate its electroporation technology for delivery of cytokine genes into hepatic colon cancer metastases. Research will include rodent studies designed to establish effective treatment protocols. Successful completion will lead to formal toxicology studies and subsequent clinical investigation of the procedure in patients with unresectable colorectal metastases, conducted under FLAIR Phase-lI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DETECTION AND PROGNOSIS OF GASTROINTESTINAL CANCER Principal Investigator & Institution: Ho, Samuel B.; Associate Professor; Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2002 Summary: Colon cancer is the second leading fatal malignancy in the United States. Prognosis and patient selection for adjuvant chemotherapy are determined by pathological and clinical staging. Previous studies have shown that colon cancer patients with lymph node metastases will benefit from chemotherapy following surgical treatment of their cancer. Survival of patients with early stage colon cancer is generally good, but a subgroup of up to 25-30 percent will relapse. Currently it is difficult to determine which patients will relapse. Characteristics of the primary tumor, such as chromosome 18q deletion or expression of sialylated carbohydrate antigens may predict subsequent prognosis, however few prospective studies exist that demonstrate the clinical utility of these markers. The applicants hypothesize that poor survival in some patients with early stage colon cancer is due to the presence of occult micrometastases at
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the time of surgery. A method for the detection of micrometastases in histologicallynegative lymph nodes using a polymerase chain reaction-based assay for one mucin type glycoprotein (MUC2) has been developed. Mucins are large glycoproteins that are highly expressed in the normal colon and in primary colon cancers. Preliminary data using this assay indicates that MUC2-positive cancer cell micrometastases can be detected in histologically-negative lymph nodes from 14 or 42 (32.5 percent) early stage colorectal cancer patients. The presence of these micrometastases correlates with greater depth of invasion of the primary tumor. In contrast, MUC2-positive cells were detected in 42/43 (98 percent) of primary cancers and were never detected in the lymph nodes from 6 patients with non-malignant colon disease. The purpose of this study is to determine if the presence of MUC2-positive micrometastases will predict which stage II colon cancer patients will have a cancer relapse or predict overall survival. A secondary purpose is to compare the sensitivity and specificity of immunohistochemical techniques to detect lymph node micrometastases and to determine the accuracy of other prognostic markers (chromosome 18q deletion and sialylated carbohydrate molecules) in this group of early stage cancers. These studies will potentially enable clinicians to more effectively identify patients with early stage colon cancer who would benefit from adjuvant therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: HISPANICS
DETERMINANTS
OF
CLINICAL
OUTCOME/TOXICITY
IN
Principal Investigator & Institution: Lenz, Heinz-Josef; Associate Professor of Medicine; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, CA 90033 Timing: Fiscal Year 2001; Project Start 03-SEP-1999; Project End 30-JUN-2003 Summary: (adapted from the investigator's abstract): The goal of this proposal is to identify the molecular determinants of CPT-11 metabolism and molecular predictors of response and survival in patients with disseminated colorectal cancer treated with CPT11. Identification of molecular determinants of CPT-11 efficacy and toxicity is of critical importance for the development of more efficient and less toxic treatment strategies for patients with colon cancer. Since its introduction as a second line of treatment for colon cancer, we have seen significant clinical toxicity in Hispanic patients treated with CPT11. One possible explanation for he increased clinical toxicity is a high frequency of a genetic polymorphism of UGT1A1, the critical enzyme essential for inactivation CPT-11 metabolites. Our preliminary data suggest that up to 60% of Hispanics have a genetic polymorphism associated with decreased enzyme activity, which is associated with high risk of significant clinical toxicity. These data facilitate the design of treatment strategies for CPT-11 that avoids life-threatening toxicity. We have also identified potential molecular determinants of response to CPT-11 in patients with colorectal cancer. Preliminary preclinical and clinical data suggest that topoisomerase I, the target enzyme of CPT-11, and genes involved in DNA repair and apoptosis may be predictors of chemosensitivity to CPT-11 treatment. The understanding of the molecular mechanism of resistance to CPT-11 will have a significant impact on the clinical management of patients with colorectal cancer. To our knowledge, molecular determinants of clinical outcome and metabolism of anticancer drugs have not been systematically studied and there are no data available in Hispanics. At USC/Norris we will be able to perform these studies because the Los Angeles County population is among the most ethnically diverse in the US. The cultural and ethnic variety provides a great "natural laboratory" for the study of colon cancer genes in most ethnic groups. We will test the hypotheses,
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1) that Hispanic patients have more frequent UGT1A1 polymorphism associated with decreased UGT1A1 activity than Caucasian, 2) clinical toxicity and pharmokinetic/ dynamics are associated with the genotype of UGT1A1, 3) the newly identified polymorphism are associated with decreased enzyme activity, 4) gene expression of topoismerase 1, bcl-2, bcl-xL, bcl-xS, bax, ICE, and p21 are predictors of response to and survival after treatment with CPT-11, and 4) that the status of DNA mismatch repair and p53 will predict for response and survival. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: DIET AND SOMATIC MUTATIONS IN COLON CANCER Principal Investigator & Institution: Slattery, Martha L.; Professor; Huntsman Cancer Institute; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2002; Project Start 01-AUG-1995; Project End 31-AUG-2007 Summary: (provided by applicant): It is most probable that both genetic and environmental factors contribute to colon cancer etiology. At present, we have the capabilities to look at the interaction between dietary intake and genes that have been linked to colon cancer. In this study, we will evaluate DNA obtained from tumor tissue from cases enrolled in a large population-based case-control study of colon cancer (CA61757; CA 48998); we propose to collect tumor blocks from a population-based casecontrol study of rectal cancer to further evaluate associations (continuation of CA48998). Tumor DNA will be analyzed to determine specific mutations and CIMP pathway phenotype. We will evaluate the associations between these genetic mutations and tumor stage at diagnosis and survival. These data will be linked to environmental data, that includes extensive information on dietary intake within the population, to determine the impact that diet has on causing these somatic mutations (location and type of mutation). Total calories, fat, protein, calcium, fiber, beta carotene, and folic acid will be assessed with these genetic mutations, as will meats (along with method of and degree of cooking), dairy products, legumes, soy products, and fruits and vegetables. Other factors such as physical activity and body size which are closely related to dietary intake will be assessed both for their associations with somatic mutations. It is hypothesized that dietary intake (as specified above), physical inactivity, and a larger body size will contribute to the CIMP phenotype. Using data from the original studies, we will use statistical methods to better define disease pathways. We will include previously collected information on p53, K-ras, and microsatellite instability in tumors as well as information on CIMP phenotype. Rectal tumors will be characterized in the same manner as colon cancer tumors were originally characterized (i.e. p53, K-ras, and microsatellite instability). Differences in colon and rectal tumors will be compared. Additionally data from rectal tumors will be combined with that from colon tumors to define disease pathways. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DIET, COLON CANCER, AND CANCER COMMUNICATIONS Principal Investigator & Institution: Abouta, Jessie S.; Nutrition; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): This application describes a career development/transition plan for Jessie A. Satia, PhD, MPH, a newly appointed Assistant Professor in the Department of Nutrition at the University of North Carolina, Chapel Hill. The candidate's overall career goal is to establish an interdisciplinary
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research career combining her background in epidemiology, nutrition, and laboratory sciences to conduct methodologic, observational, and intervention studies of diet and human cancers. In particular, she would like to conduct studies to identify risk factors for cancer and design appropriate interventions for prevention and control in minority and underserved populations. The candidate proposes a career development plan that includes: teaching and mentoring students; submitting research manuscripts and pilot project proposals; and a research plan (75% of her effort) with two proposed projects. Project 1 titled "Cancer Communications among African American Adolescents" aims to collect information necessary to design diet-related cancer prevention messages for African American adolescents; and evaluate the effectiveness of messages framed in different ways on knowledge, attitudes, beliefs, and intentions to improve diet in this population. Qualitative methods will be used to collect information on various factors that affect dietary behavior among African American adolescents (14 to 16 years) in Durham, NC. This information will then be used to design messages focused on lowering dietary fat intake in this population that will be delivered via the Internet. Participants will be randomized into four groups based on Prospect theory and message framing, and will complete pre- and post-tests and cognitive interviews to assess the short-term impact of the framed messages. Project 2, "Diet and Colon Cancer in African Americans and Whites in North Carolina" describes proposed analyses using previously collected data from a study of 654 colon cancer cases (40-80 years) and 1067 populationbased controls, with equal numbers of African Americans and whites, in a 33-county area of North Carolina. The specific aims of the analyses proposed here are to examine effects of dietary factors (e.g., fat, fruits, vegetables, antioxidants, fiber, alcohol, and total calories) and food intake patterns (meal frequency and snacking timing) on colon cancer risk. Potential future research opportunities using biological specimens from this study are described. The long-term success of cancer research efforts rests, in part, on building the career of talented young faculty. Obtaining this award will greatly broaden and strengthen the candidate's focus on cancer prevention and control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: DISPARITIES IN CARE: OBESITY AND CANCER SCREENING Principal Investigator & Institution: Wee, Christina C.; Beth Israel Deaconess Medical Center St 1005 Boston, MA 02215 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 29-SEP-2003 Summary: Obesity is the second leading cause of preventable deaths. Cancers of the colon, prostate, breast, and cervix account for many of these deaths. Despite their higher risk, preliminary analyses suggests that women with obesity may be screened less often than women without obesity for breast and cervical cancer. Whether disparities in cancer screening extend to men with obesity is unknown. Because of cultural and gender differences in self- perception, race and sex may also influence the relationship between obesity and disparities in screening. This project will use national data collected as part of the 1998 National Health Interview Survey (NHIS) and the 1996 Medical Expenditure Panel Survey (MEPS) to 1) compare the rates of screening for colon, prostate, breast, and cervical cancer between persons with and without obesity based on national screening guidelines, 2) examine whether differences in cancer screening rates associated with obesity vary by sex and race, and 3) examine whether differences in screening rates can be explained entirely by the higher illness burden experienced by persons with obesity. Using statistical modeling, the investigators will quantify differences in screening rates between persons with and without obesity after accounting for sociodemographic factors (such as age, race, education, income, region of
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the country), access to care, and medical conditions. The investigators will also examine the association between weight and cancer screening in different racial subgroups. For colon cancer screening, the relationship between obesity and screening will be examined among men and women separately. Findings from this project will help determine whether obesity is a barrier to cancer screening and help researchers and clinicians begin to understand factors that contribute to disparities in screening. Recognizing and understanding the role of obesity as a potential barrier to care is the first step towards improving quality of care for patients with obesity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: DNA REPAIR AND COLON CANCER Principal Investigator & Institution: Meuth, Mark L.; Professor; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2001 Summary: Colon carcinogenesis is a multi-step process dependent upon the accumulation of mutations in tumor suppressors and proto-oncogenes. Recent work indicates that an inherited form of colon cancer (HNPCC) the accumulation of mutations may be driven by the loss of mismatch repair. Cells losing this repair pathway have a distinctive mutator phenotype including microsatellite instability, a high rate of spontaneous mutation, and resistance to DNA alkylating agents. Our understanding of the biological consequences of mismatch repair deficiency stems largely from studies of colon cancer cell lines. However, these lines have many other alterations that could contribute to the mutation phenotype. In Specific Aims 1 and 2 the hypothesis that mismatch repair deficiency is sufficient for induction of the mutation phenotype seen in these colorectal carcinoma cell lines will be tested. In Aim 1 the ability of inducible cDNA expression constructs of the mismatch repair genes to correct the mutator phenotype in repair deficient colon cancer cell lines will be investigated. Dominant negative alleles of the mismatch repair genes that can induce a mutator phenotype in repair proficient cell lines will be sought in Aim 2. Expression constructs of mutant forms of these mismatch repair cDNAs will be introduced into repair proficient cell lines (in particular non-tumorigenic cell lines of epithelioid origin) to determine the effects on spontaneous mutation rate, cell cycle checkpoint controls, and apoptosis. The strength of this approach is the use of isogenic repair proficient and deficient cell lines to determine effects on the determinants of genome stability and cell growth. In Specific Aim 3 the lethal effects of over-expression of the mismatch repair cDNAs will be examined by microinjection of wild type and mutant constructs. This will test the hypothesis that the mismatch repair genes are involved in cell cycle regulation. In Specific Aim 4 the role of the mismatch repair homologs in the repair process will be determined by the manipulation of these genes in cultured cells. Long term objectives are reflected in Specific Aim 5 where we will determine whether mutations of these genes in cultured cells. Long term objectives are reflected in Specific Aim 5 where we will determine whether mutations of other repair genes contribute to inherited forms of colon cancer. These studies should significantly improve our understanding of the role of mismatch repair deficiency in early events of colon carcinogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DUTPASE AS A PROGNOSTIC MARKER IN COLON CANCER Principal Investigator & Institution: Ladner, Robert D.; Assistant Professor; Molecular Biology; Univ of Med/Dent Nj-Sch Osteopathic Med Osteopathic Medicine Stratford, NJ 08084
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Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): For more than 40 years, thymidylate metabolism has been an important biochemical target for widely utilized anti-cancer agents. Inhibitors of this pathway such as the fluoropyrimidines and antifolates induce a severe depletion of TTP pools resulting in nucleotide pool imbalance and cell killing through a process termed "thymineless death." Investigation of the underlying mechanisms of this process suggest that aberrant uracil-DNA metabolism may be an important mediator of DNA damage and cell killing. The broad objectives of this proposal are to better understand the role of key enzymes involved in dUTP metabolism in modulating chemosensitivity. In this study, we propose to investigate the prognostic value of the enzyme deoxyuridine triphosphate nucleotidohydrolase (dUTPase) as a marker for overall survival and response to fluoropyrimidine-based chemotherapy in metastatic colon cancer. dUTPase catalyzes the hydrolysis of dUTP to form dUMP and PPi, thereby eliminating dUTP from the DNA biosynthetic pathway. We hypothesize that dUTPase overexpression counters the cytotoxic effect of fluoropyrimidine treatment by limiting the expansion of dUTP pools. Although there is significant evidence suggesting that uracil-DNA metabolism may be a critical factor in mediating cytotoxicity, there have been few clinical studies performed to clarify the role of human dUTPase expression in modulating chemosensitivity. Specific aim 1 investigates the significance of dUTPase expression in predicting patient response to fluoropyrimidine-based chemotherapy and overall survival in metastatic colon cancer. Specific aim 2 compares the prognostic ability of intratumoral dUTPase expression with other known prognostic markers of colorectal cancer including, thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and p53. Clinical analysis of dUTPase expression as a prognostic marker will not only provide a useful tool for the evaluation and treatment of colon cancer patients, but will also provide additional insight into the role of aberrant uracil-DNA metabolism in chemotherapies that inhibit thymidylate metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: EFFECT OF PLANT PHENOLIC COMPOUNDS ON HUMAN COLON EPITHELIAL CELLS Principal Investigator & Institution: Shiff, Steven J.; Associate Professor of Clinical Investig; Rockefeller University New York, NY 100216399 Timing: Fiscal Year 2001 Summary: Colorectal cancer is a common and often fatal cancer. Primary prevention of this important public health problem is feasible because it is substantially influenced by nutritional and pharmacological factors such as dietary fat, fiber, micronutrients (i.e. calcium and selenium, aspirin (ASA), and other nonsteroidal antiinflammatory drugs. Sulindac is a potent chemopreventive agent for colorectal cancer. Quercetin, a plantderived compound with anti-inflammatory properties, inhibits colon cancer development in preclinical studies. However, its effectiveness in the prevention of human colorectal cancer is unknown. NSAIDs modulate the turnover (induce cell quiescence and apoptosis) of colonic epithelial cells. This effect may be important for their efficacy as colon cancer chemopreventive agents. The goal of this study is to determine the effects sulindac and quercetin on the turnover of human colonic epithelial cells. By comparing and contrasting the effect of these 2 compounds on colonocytes of humans, we hope to begin to understand the effects of NSAID compounds on the physiology of the colorectal crypts of humans. Through these and future studies we eventually hope to predict the potential utility of quercetin as a colon cancer
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chemopreventive agent and to shed additional light on the mechanisms by which antiinflammatory agents prevent colon carcinogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: EFFECTS OF BRASSICA ON MARKERS OF COLON CANCER RISK Principal Investigator & Institution: Fowke, Jay H.; Medicine; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2001; Project Start 06-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant): There is considerable basic science research to suggest that isothiocyanates (ITC) or several indole analogs (e.g., indole-3carbinol (I3C)) slow cellular proliferation, re-instate apoptotic action, and reduce colon tumor incidence. Humans are exposed to these agents primarily through consuming Brassica vegetables (e.g., broccoli), but it is unknown if greater Brassica consumed could affect colon cancer risk. We propose a short-term pilot dietary intervention to investigate the effects of greater Brassica consumption on markers colon cancer progression. Twenty adenoma patients will participate in a randomized controlled cross-over trial. Recruitment, intervention, and lab protocols have been developed through other ongoing studies, improving the cost-efficiency of this pilot project. The intervention-arm of the trial is based on a model developed for the Women's Health Initiative, and provides social support and information to help participants incorporate these vegetables into their daily diet. Biomarkers measured from rectal biopsies will include Bcl-2 (inhibits apoptosis), Bak and Bax (promote apoptosis), Mib-1 (marker of cellular proliferation), and p21 (marker of cellular differentiation). Multiple 24-hour dietary recalls will measure each participant's adherence to the intervention. Dietary adherence will be measured further by urinary ITC level (combined with GST enzyme genotype), a unique and specific biomarker of Brassica vegetable intake. Using mixed-model repeatedmeasures ANOVA, we will compare molecular marker expression when participants consume Brassica vegetables to when these same participants consume an over-thecounter fiber and vitamin supplement. This pilot study will provide the needed estimates of variance in biomarker response to the dietary change for sample size calculations for future applications. Previously, we found that healthy people were able to increase the consumption of these vegetables with minimal social and instructional support, and we used those pilot data to gain funding for a larger randomized trial enrolling breast cancer survivors. Since Brassica vegetables are widely available, inexpensive, and consumed without harm, a change in molecular marker expression consistent with reduced proliferation and enhanced differentiation and apoptosis would suggest further research to evaluate the application of Brassica consumption to reduce colon cancer risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECTS OF ORGANIC SELENIUM AGAINST COLON CANCER Principal Investigator & Institution: Nelson, Mark A.; Professor; None; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Colorectal cancer is the third leading cause of cancer death in both males and females in the U.S. Thus, the development of dietary and novel chemopreventive approaches for this segment of the population could provide a practical approach for significantly reducing colon cancer occurrence. Recent studies indicate that supplemental Se (in the form of high selenium containing yeast) reduces
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cancer risk in humans. However, the mechanism by which organic selenium exerts its anticancer effects remains to be identified. Selenomethionine is the predominant form of selenium in the yeast. We have developed evidence indicating that selenomethionine, inhibits Cox 2 protein expression in colon cancer cells. Thus, the first hypothesis to be tested is that the anticancer effects of dietary selenium (in the form of Se-yeast or selenomethionine) are mediated, in part, by inhibition of cyclooxygenase 2 (COX-2) activity. We also have evidence for a COX-2 independent mechanism. We can demonstrate alterations in cyclin A, cyclin B, and p34 cdc2 phosphorylation in selenomethionine treated colon cancer cells. These observations lead to the second hypothesis of the proposed studies that selenomethionine causes growth arrest by inappropriate expression of cyclins A and cyclins B as well increased phosphorylation of p34cdc2. To test our two main hypotheses, the three specific aims are performed 1) To determine the molecular basis of the effects of selenomethionine on COX-2 protein expression. 2: To investigate the role prostanoid receptors play in mediating the downstream effects of PGE2 in selenomethionine-induced growth inhibition. 3: To identify the mechanism for the COX-2 independent anti-cancer effects of selenium. We have a unique opportunity to translate our basic science experimental findings to clinical intervention trials. The data from these studies will identify the key mechanisms involved in the anticancer effects of selenium and increase understanding of eicosinoids in the biology of colorectal cancer. The greatest impact is realized by the provision of new molecular markers for the efficacy of selenium compounds for clinical intervention trials and the development of novel molecular targets for therapeutic intervention strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: EPIDEMIOLOGY OF LOSS OF IMPRINTING IN COLORECTAL CANCER Principal Investigator & Institution: Cruz Correa, Marcia R.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 02-JUL-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Dr. Cruz-Correa is currently completing the requirements of both a gastroenterology fellowship at Johns Hopkins Hospital and a Ph.D. in Clinical Investigation through the Graduate Training Program in Clinical Investigation, a joint initiative of the Johns Hopkins School of Medicine and the School of Hygiene and Public Health. She has successfttlly completed the preliminary Ph.D. oral exam, which covered fundamental concepts given during the first year of formal didactic training at the Johns Hopkins School of Hygiene. Her immediate career goals are the completion of her doctorate in Clinical Investigation, the publication of its results, and an appointment to the faculty of Johns Hopkins. Her long-term objectives are to become a leader in the field of gastrointestinal oncology with emphasis in genetics, outcomes and prevention. The Departments of Medicine and the Graduate Training Program are fully committed to the development of Dr. Cruz-Correa's career. This award will enable her to acquire the necessary skills to develop a successful career in clinical research under the guidance of her mentor, Dr. Francis Giardiello, her thesis advisor, Dr. Neil Powe and the additional mentorship of Dr. Andrew Feinberg, Dr. Gloria Petersen and Dr. Scott Zeger. The overall goal of this project is to characterize the role of loss of imprinting of the IGF-2 gene in colorectal cancer. LOI in colon cancer was found both in the tumor as well as in the normal mucosa of over 40 percent of the cases. This is the first time that a gene alteration has been described in such a high frequency in the norrnal tissue of cancer patients in the general population. This finding suggests
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that LOI in normal tissue could identify a subgroup of patients at risk of colon or other cancers. LOI has potential as a new biomarker for cancer predisposition in the colon and in extracolonic sites. An explorative study to evaluate the prevalence of LOI in people with normal colons, and those with colonic polyps and cancer is proposed using a crosssectional study design, followed by a prospective cohort of patients with and without LOI of the IGF-2. Analysis of the fundamental characteristics of LOI in the IGF-2 gene will enable the determination of whether LOI at this locus is a risk factor for the development of colorectal cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: ERBB2 KINASE SIGNALING IN COLON CARCINOGENESIS Principal Investigator & Institution: Dawson, Dawn M.; Pathology; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001; Project Start 21-AUG-2000; Project End 31-JUL-2005 Summary: Altered or over-expression of growth factors or their receptors is thought to significantly contribute to tumorigenesis. The erbB kinases, especially the protooncogene erbB2, and major ligands (EGF and neuregulin groups) are implicated in epithelial malignancies such as breast and colon. EGFR and TGFalpha co- expression in colon cancer is associated with neoplastic progression through growth factor independence. Immunohistochemical studies of the erbB kinase family in colon adenomas with concurrent invasive cancer demonstrate increased expression of erbB2 in the neoplastic cell population. In addition, I present the new finding of co-expressed heregulin (cognate ligand for human erB3 and 4) and erbB2 in these polyps and cancers as well as in colon adenoma and carcinoma cell lines. I demonstrate a significant biologic response to heregulin, not previously described in colon cell lines, and loss of cell growth by blockade of the erB2 receptor, emphasizing the importance of activated erbB2 as a mechanism for cell growth in the colon. As both EGFR and erbB3 will signal through erbB2 as heterodimers, I propose that activation of erbB2 is central to the control of down stream signaling and that activated erbB2 receptor is pivotal in the progression of colon cancer. To study the role of erbB2 and related kinases and ligands in colon carcinogenesis, four colon cell lines have been characterized for the role of erbB signaling: a benign adenoma line, two growth factor dependent (GFD) carcinoma lines, and a growth factor independent (GFI) carcinoma cell line. They were selected to represent stages in the multi-step progression of colon carcinogenesis. Blockade of EGFR and erbB2 receptor activation in these cell lines is associated with dramatic biologic response further supporting a role for functional erbB2 on colon carcinogenesis. Employing these unique cell lines, representative of colon cancer progression that exhibit autocrine activation by TGFalpha and heregulin, I propose to study erbB2 signaling in colon carcinogenesis. The objective is to define the role of the erbB2 activation through TGFalpha and heregulin in this in vitro model of tumor progression, specifically to determine: 1) the functional expression profile of the erbB kinases and these ligands in the model cell lines and characterize tissue expression of the same to support the biologic relevance of erbB kinases in carcinogenesis, 2) the signal pathways and biologic response mediated by erbB2 activation, and 3) the effects of erbB signalbased modulation through erbB2, PI3K, and MED/MAPK pathways that contributes to neoplastic progression as characterized by cell growth and resistance to apoptosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EXERCISE INTERVENTION IN COLORECTAL POLYP PATIENTS Principal Investigator & Institution: Mctiernan, Anne M.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, WA 98109 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-JAN-2004 Summary: (Adapted from the Applicant's Abstract): Strong observational evidence points to a link between physical activity and reduction in risk of colon cancer. The mechanisms for this association have not been delineated, nor have the amounts and types of exercise needed for a putative protective effect been determined. We propose a randomized controlled clinical trial of a one-year moderate aerobic/strength training exercise intervention in adenomatous colon polyp patients (n=100 men, 100 women). We hypothesize that polyp patients in an exercise intervention will experience significant biological effects on colorectal epithelium, specifically Ki67 indices of proliferation, bax and bc1-2 markers of apoptosis, and prostaglandin concentrations (PGE2 and PGF2cc). Patients will be recruited on-site from gastroenterology physicians' offices and secondarily from a high-risk colorectal cancer family registry. Sedentary individuals with newly diagnosed (within the past 18 months) adenomatous colon polyp(s) will be screened for eligibility and randomized to either the exercise intervention or a stretching-control group. The exercise intervention will use existing proven methods for adopting and maintaining exercise, taken from our ongoing research program. It will consist of 3 months' facility-based exercise instruction in small groups, followed by 9 months' home-based exercise program supplemented with group behavior change meetings. The goal for exercise will be moderate-level aerobic exercise 5-6 days per week for 30-45 minutes, plus strength training 2 days per week for 15-20 minutes. Colon and rectal biopsies will be taken at baseline and 12-months, and examined for amount and patterns of epithelial cell proliferation (with Ki67 marker) and apoptosis markers (bc1-2 and bax, an inhibitor and an inducer of apoptosis, respectively). Additional potential markers of exercise effect on colon cancer risk will be measured, including rectal mucosal biopsy prostaglandin concentrations, stool frequency, insulin-like growth factor (IGF-1) and IGF binding protein (IGFBP-3), insulin, glucose, C-peptide, triglycerides, and measures of fat mass and fat distribution. Other measures at baseline and 12 months include fitness (V02max), self-reported physical activity, diet, and quality of life. Results from this unique human experimental study will provide important information about mechanisms of exercise effects on colon carcinogenesis and about potential Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EXPERIMENTAL THERAPY OF COLON CANCER WITH ANTISENSE FUTS Principal Investigator & Institution: Weston, Brent W.; Pediatrics; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: (adapted from the investigator's abstract): The prognosis of colorectal cancer is adversely affected by liver metastasis, and therapeutic options are limited for advanced disease. Rolling of carcinoma cells along vascular endothelium is mediated through selectin adhesion receptors and their ligands, sialyl Lewis x (sLex) and sialyl Lewis a (sLea). Biosynthesis of these glycans on human colon cancer cells is largely controlled by the alpha(1,3)fucosyltransferases FUT3 and FUT6. Stable transfection of carcinoma cells with antisense FUT3/FUT6 sequences inhibits expression of sLex/sLea, selectin-mediated adhesion, and liver metastasis in nude mice. The proposed
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experiments extend these results to an in vivo pre-clinical model with FUT antisense oligodeoxynucleotides (AS-ODNs) against highly metastatic HT29-LMM colon carcinoma cells and locally invasive, non-metastatic COLO-205 colon cancer cells. The long-term goals are to extend the use of AS-ODNs to adjunctive treatment of colon carcinoma metastasis and to contribute to the study of glycosyltransferase gene regulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: EXPRESSION MONITORING IN COLORECTAL CANCER Principal Investigator & Institution: Notterman, Daniel A.; University Professor and Chair; Weill Medical College of Cornell Univ New York, NY 10021 Timing: Fiscal Year 2002; Project Start 30-AUG-2002; Project End 30-JUN-2006 Summary: Our long-term objective is to describe the molecular events that underlie colorectal cancer. Advances in technology permit the simultaneous measurements of thousands of different mRNA transcripts. There have also been notable advances in rapidly and efficiently scoring DNA abnormalities in mathematical approaches for organizing and exploring this information. Our plan is to harness all of these abilities in the service of a molecular understanding of tumor formation, progression, and metastasis. This should both enable us to discern new cancer pathway genes and to replace the current morphological classification of cancer with a more precise system based upon the molecular state of the abnormal cell. Our specific aims are: (i) Array Development: To develop and validate a colon cancer cDNA microarray. Using the Affymetrix U 95 Chip Set (60,000 full-length genes and ESTs), we will screen 120 microdissected tissue samples (90 abnormal, 30 normal) representing the full range of colorectal neoplasia. Approaches that are delineated and described in Project 3 will be used to select 4,000 to 6,000 features for a colon-oriented cDNA microarray. Features representing other known or suspected cancer pathway genes (see Project 1, and from the literature) will also be included in the colon-oriented cDNA microarray array. (ii) Gene Discovery: To identify expression changes in individual and groups of transcripts as colonic epithelium is transformed through aberrant crypts, adenomatous polyps, adenocarcinomas, and metastatic tissue. To target the associated genes for mutational analysis (in concert with Project 1 and Project 3) and assess their role in neoplasia. Genes will be identified that are abnormally expressed in neoplastic epithelium and in concert with Project 1 are shown to have an associated genetic or epigenetic abnormality. These candidate oncogenes or tumor suppressor genes will be characterized by: (i) in situ hybridization, (ii) promoter and coding sequence analysis, (iii) clonogenic and tumorigenic assays, (iv) cell cycle analysis, (v) animal models, and (vi) mechanistic studies. (iii) Outcome prediction: To develop a molecular taxonomy of colorectal cancer by relating concerted patterns of gene expression to clinical and genetic information. In concert with Projects 1 and 3, we propose to develop an approach to tumor classification and clinical outcome prediction that is grounded in a comprehensive evaluation of transcript abundance, DNA markers, and clinico-pathological status. By relating patterns of gene expression and gene mutation to fundamental indicators of disease status, we may be more able to precisely predict the clinical behavior of a tumor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FLAVONOID MODULATION OF EPITHELIAL MIGRATION /SIGNALING Principal Investigator & Institution: Hord, Norman G.; Food Science & Human Nutrition; Michigan State University 301 Administration Bldg East Lansing, MI 48824
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Timing: Fiscal Year 2003; Project Start 02-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Colorectal cancer, the third leading cause of cancer death in men and women in the U.S., results from the interaction of genetic and dietary susceptibility elements. Since colorectal cancer is caused by failure of terminal cell differentiation, dietary factors that promote cell migration, a required phenotype for cell differentiation, can be expected to decrease colorectal cancer risk. Our long-term goal of this research is to identify mechanisms by which specific dietary compounds mediate the development of phenotypes associated with cell differentiation including migration, cell-cell communication and apoptosis. The objective of this application is to identify the intracellular signaling pathways induced by flavonoids that contribute to cell migration. Our central hypothesis is that specific flavonoids, present in the diet in foods and beverages, will elicit the migratory phenotype in non-tumorigenic colon epithelial cells by activating specific intracellular signaling pathways. Wild-type adenomatous polyposis coil (APC) is a gatekeeper gene for inherited and sporadic colorectal cancer in rodents and humans. The migratory phenotype is dependent upon wild-type APC expression since full length APC protein mediates directed cell migration in the colon. We will use non-tumorigenic colon epithelial cell lines with normal Apc genotype (called YAMC) and mutant Apc genotype (called IMCE) to identify biological determinants of cell migration relevant to the early stages of colon tumorigenesis. To test our hypothesis and achieve our objectives, we propose to address three specific aims. First, we will identify specific flavonoids that induce migration in YAMC and IMCE cells by performing dose-response studies of flavonoid-dependent cell migration using twelve (12) compounds representing five (5) flavonoid families. Second, we will quantify the ability of migration-inducing flavonoids to activate relevant cell signaling pathways associated with cell migration by co-treating YAMC and IMCE cells with flavonoids and receptor- and signaling pathway-specific antagonists or inhibitors. Third, we will quantify the ability of selected migration-inducing flavonoids to modulate gene expression in YAMC and IMCE cells using cDNA microarrays constructed from the 15K mouse set of the National Institute of Aging. These analyses will identify genes and clusters of gene families whose transcription is increased or decreased in response to these flavonoids. The identification of dietary compounds which could stimulate migration, and hence, cell differentiation, in cells expressing mutant Apc (IMCE cells) could define a new strategy for prevention of colon cancer by diet-derived compounds. Ultimately, this research will provide critical information necessary for specific and rational dietary recommendations to decrease colon cancer risk in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: FLUORESCENT CARBOHYDRATES
TAGS
TARGETED
ON
CELL
SURFACE
Principal Investigator & Institution: Wang, Binghe; Professor; Chemistry; North Carolina State University Raleigh 2230 Stinson Drive Raleigh, NC 27695 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2002 Summary: Malignant transformation is often associated with alteration of cell surface carbohydrates. The expression or over-expression of certain carbohydrates, such as sialyl Lewis X (sLex), sialyl Lewis a (sLea), Lewis X (Lex) and Lewis Y (Ley), has been correlated with the development of certain cancers. These cell surface carbohydrates can be used for cell-specific identification and targeting of carcinoma cells. The long-term goal of this project is the development of small molecule artificial receptors which can recognize target carbohydrate structures with high selectivity and affinity. Such
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receptors could be used for the development of fluorescent tags for cell- specific identification, tissue-specific imaging (such as MRI), and targeted delivery of therapeutic agents. In this study, we will use sLex as the model carbohydrate and use colon cancer as the model biological system because the expression of sLex is often associated with progression and metastasis of colon cancer. The short-term objective of this application is to develop tissue-specific fluorescent tags (sensors) which can recognize sLex with high affinity and selectivity. For the construction of such fluorescent sensors, we plan to use an integrated approach combining template-directed synthesis, combinatorial chemistry, and computer molecular modeling aided design. The sLex-specific artificial receptors have the potential to be used for cell identification, detection and tagging for the purpose of localization, staging, tissue biopsy, and fluorescence-directed surgical removal of colon cancer cells. Such tissue-specific compounds could also serve as vehicles for targeted delivery of cancer chemotherapeutic agents. These small molecule sensors may also have the following advantages over antibody-based detection/delivery systems: (1) greater stability during storage and in vivo; (2) increased permeability through biological membranes and, therefore, enhanced target accessibility; (3) intrinsic sensitivity to binding with significant fluorescence intensity increases, making detection and visualization easier and more suitable for high throughout screening, and (4) lower propensity to elicit undesirable immune responses. Similar methods, once developed, could also be used for the construction of fluorescent tags for other cell surface carbohydrates implicated in human malignancies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: FOLATE, 1-CARBON NUTRIENTS, GENE VARIANTS & COLON CANCER Principal Investigator & Institution: Hunter, David J.; Director; Epidemiology; Harvard University (Sch of Public Hlth) Public Health Campus Boston, MA 02460 Timing: Fiscal Year 2003; Project Start 18-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Most of the over twenty epidemiologic studies that have examined the relationship between dietary folate intake and the risk of developing colorectal neoplasms, have reported that higher folate intakes are associated with lower risk. Animal studies, using either carcinogen-induced or genetically engineered rodent models of colorectal cancer, have indicated an inverse relationship between dietary folate and the risk of colorectal cancer. The folate metabolic pathway influences genomic methylation and the supply of nucleotides for DNA synthesis; these can also be influenced by adequacy of supply of vitamins B12, B6, and B2, all co-factors for critical enzymatic reactions in the pathway. The overall long-term objective of our Team is to establish the role of folate and other nutritional contributors to one-carbon metabolism in colorectal cancer by combining animal, mechanistic, human observational studies and clinical trials. We will accomplish this by establishing a Cooperative Specialized Center for the study of Folate, One carbon nutrients, Gene variants and Colorectal cancer. This Center will be a Collaborative Program between Harvard and Tufts Universities in Boston, Dartmouth University in New Hampshire, the International Agency for Research in Cancer and the University of Bergen in Europe, Variagenics Inc. in Boston, and the Division of Cancer Prevention and the Center for Cancer Research at the NCI. We are organized into three projects, developmental projects, and two cores. Project 1 will pool data from three large prospective cohort studies with 2,700 expected colorectal cancer cases to establish whether higher intake of folic acid reduces risk of colorectal cancer and examine whether this reduced risk is greater among persons with
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low methionine intake, low plasma folate, vitamins B12, B6, and B2 levels, consumers of more than one alcoholic beverage per day, and homozygotes for the methylenetetrahydrofolatereductase (MTHFR) C677T polymorphism, and compound heterozygotes for the MTHFR A1298C polymorphism. Project 2 will validate mouse models of colon carcinogenesis as systems to examine modification of risk by folate and other contributors to one-carbon metabolism. Project 3 will assess whether the degree of uracil misincorporation and genomic methylation in peripheral blood lymphocytes and distal colon biopsies represent biomarkers of one-carbon nutrient adequacy and colorectal adenoma risk, using data and samples from two randomized clinical trials of folate supplementation. The projects will be supported by innovative Developmental Projects. In initial Developmental Project 1 transgenic mice with the null allele of MTHFR, and the homologous C677T polymorphism; these mice will be available for incorporation into feeding studies in Project 2. In Developmental Project 2 we will explore five folate-metabolism genes for polymorphisms that influence plasma folate and homocysteine levels. All Projects will be supported by the Administrative and Statistical Core (based at the Harvard School of Public Health), and the Measurement Core (based at the Human Nutrition Research Center at Tufts University). These highly interrelated studies will help integrate epidemiologic and mechanistic observations and help provide a basis for public health recommendations on optimal levels of folate and B vitamin intake. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: INVASION
FUCOSYLATED
CELL
SURFACE
MOLECULES
IN
TUMOR
Principal Investigator & Institution: Domino, Steven E.; Obstetrics and Gynecology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2002; Project Start 18-JUN-2002; Project End 30-APR-2006 Summary: (provided by applicant): Fucosylated oligosaccharides have been implicated in multiple cell-cell interactions in inflammation and cell trafficking, differentiation and development, and malignancy. While descr iptive and functional data support the major hypothesis that alpha(1,2)fucosylated CD44 and other molecules mediate progression of metastatic adenocarcinoma from several epithelial cancers, definitive demonstration of the function of these cell surface epitopes in carcinogenesis is lacking. The long range goal of my research is to determine how alpha(1,2)fucosylated oligosaccharides are involved in cancer progression, with an intent of developing novel approaches to treat metastatic cancer with anti-adhesion therapies based on cell surface oligosaccharides. The approach I have chosen is to ablate in mice the transferase enzymes Fut1 and Fut2 required to generate alpha(1,2)fucosylated oligosaccharides. I am uniquely positioned to accomplish the proposed work as I have developed two knockout mouse lines and have enlisted the collaborators necessary for completion of this project. Because multiple glycosyltransferases are expressed in cancer cells, I have chosen to focus on the alpha(1,2)fucosyltransferase enzymes to either support their importance in neoplasia, or eliminate them from further consideration in the development of potential therapeutic targets. I propose the following Specific Aims: 1) To classify in non-neoplastic tissues the a l p ha(1,2)fucosyltransferase (Fut1 or Fut2) that synthesizes alpha(1,2)fucosylated H, Lewis B, and Lewis Y oncofetal antigens in order to assign a specific transferase gene to the expression of a specific set of cell surface oligosaccharides over-expressed in tumors. 2) To correlate expression of Fut1 and Fut2 with histologic progression of spontaneous colorectal tumors in mice carrying germline inactivating mutations in the transforming
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growth factor-beta signaling gene Smad3. 3) To test the importance of alpha(1,2)fucosylated oligosaccharides in colon cancer in vivo by determining the rate and extent of progression of colon tumors in Smad3 null mice. and in 1,2dimethylhydrazine-induced tumors, in the presence and absence of cell surface alpha(1,2)fucose by crossing mice into the Fut1 and Fut2 null background. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: GASTRIN-RELEASING PEPTIDE RECEPTOR DESENSITIZATION Principal Investigator & Institution: Benya, Richard V.; Medicine; University of Illinois at Chicago 1737 West Polk Street Chicago, IL 60612 Timing: Fiscal Year 2003; Project Start 01-SEP-1997; Project End 31-JAN-2008 Summary: (provided by applicant): The objective of this proposal is to determine the degree to which functional gastrin-releasing peptide receptors (GRP-R) are expressed in colon cancer, and to elucidate the mechanism(s) by which these receptors regulate the differentiation of individual colon cancer cells when expressed in functional form. We have previously shown that the GRP-R acts as a morphogen, critically regulating colon cancer differentiation (Cell Growth Diff 2000; 11: 385). We have also shown that GRP-R mRNA is aberrantly expressed by all human colon cancer cell lines studied but is frequently mutated and rendered pharmacologically non-functional (Mol Pharmacol 2000; 58: 601). In our Preliminary Data we show that the X-linked GRPR gene is also mutated in archived human colon cancers, with mutation number increasing as tumor cells de-differentiate. Poorly differentiated tumor cells contain GRPR gene mutations that cause receptor inactivation whereas this is never seen in well differentiated cells. Thus we propose the mechanistic hypothesis that expression of functional GRP-R within any particular colon cancer primarily regulates tumor cell differentiation; with receptorinactivating mutations representing a major mechanism allowing tumor cells to dedifferentiate. However the extent and effect of these mutations on GRP-R behavior, and the mechanism(s) by which expression of functional receptor modulates tumor cell appearance, have not been determined. Specific Aim 1 focuses on elucidating the mechanism(s)whereby functional GRP-R modulate tumor cell differentiation. In our Preliminary Data we show that Caco-2 cells variably express GRP-R, which when present regulates normal morphological progression by activating focal adhesion kinase (FAK). Caco-2 cells will be transfected with vectors under control of an inducible promoter allowing for the directed expression of mini-genes. The products of these mini-genes will block specific regions of the GRP-R from binding to any G protein, or block specific G proteins themselves. The ability of each construct to undergo normal morphological progression will then be assessed. Specific Aim 2 is directed to identifying mutations in the GRPR gene in human colon cancers as a function of the differentiation of individual tumor cells. Archived colon cancers maintained in the GI Tumor Bank will be randomly selected and all cells of defined differentiation removed by laser capture microscopy. The GRPR gene will be isolated, and all mutations identified recreated by site-directed mutagenesis so that they can be evaluated in a transiently transfected cell system. Overall these studies will provide critical information regarding colon cancer differentiation, and shed light on a novel mechanism regulating the inactivation, or desensitization, of a clinically important heptaspanning receptor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE EXPRESSION OF COLON CANCERS THAT METASTASIZE Principal Investigator & Institution: Markowitz, Sanford D.; Ingalls Professor of Cancer Genetics; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001; Project Start 30-AUG-2000; Project End 31-JAN-2005 Summary: This proposal will test the hypothesis that differences in patterns of gene expression determine the differing biologic behaviors between colon cancers that are curable with primary surgical therapy and those that ultimately metastasize to the liver and kill. Additionally, we hypothesize that in colon cancer primary tumors, only a minority of cells will be "prometastatic", that is competent to give rise to liver metastases, and that assays of whole primary tumor lysates may thus fail to distinguish the crucial presence or absence of this "prometastatic" subpopulation. To test these hypotheses, Dr. Sanford Markowitz and his colleagues in the cancer genetics program at the Case Western Reserve University-NCI designated Comprehensive Cancer Center have forged a collaboration with Eos Biotechnology, Inc., a leader in gene expression array technology. The collaboration aims to establish an accurate molecular classification of colon cancer by focusing on a unique collection of surgically resected colon cancer liver metastases, all of whose cells have in vivo demonstrated metastatic ability. Using the Affymetrix human 40K GeneChip expression array technology, these investigators will generate a comprehensive description of global gene expression of these liver metastases. Comparing these liver metastases versus control nonmetastatic colon cancers, that were all cured by surgical excision, will specify a set of metastases specific genes whose expression defines a "metastatic signature." The goal of identifying those colon cancer primary tumors that can metastasize will be achieved by showing that they bear "prometastatic" cells recognizable by in situ hybridization assay of "metastatic signature" genes. Project aims are: i) To elucidate the "metastatic signature" by comparing on Affymetrix arrays colon cancer liver metastases versus non-metastatic colon cancer primary tumors. ii) To identify among metastases signature genes those specifying early metastatic events detectable by array analyses of colon cancer primary tumors that did metastasize. iii) To use in situ hybridization to confirm the metastatic signature of liver metastases arises from colon epithelial cells. iv) To use in situ hybridization to detect expression of metastatic signature genes by prometastatic cells in colon cancer primary tumors that are simultaneous with lever metastases or are precursor of liver metastases relapse. v) To use in situ hybridization to determine the areas of maximum concentration of "prometastatic" cells in colon cancer primary tumors. vi) To validate the metastatic signature and show it has prognostic power in an independent validation archive of 350 colon cancers. vii) To develop immunohistochemical assays for detection of the metastatic signature. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE-ENVIRONMENT CARCINOGENESIS
INTERACTION
AND
COLON
Principal Investigator & Institution: Chen, Jia; Community and Preventive Med; Mount Sinai School of Medicine of Nyu of New York University New York, NY 10029 Timing: Fiscal Year 2001; Project Start 21-SEP-1998; Project End 31-AUG-2003 Summary: Jia Chen received her Sc.D. in 1994 in the fields of Toxicology and Environmental Engineering from Massachusetts Institute of Technology. Since 1995 she has been working as a Research Associate in Medicine at Harvard Medical School and a Research Fellow at Harvard School of Public Health. She is interested in an academic
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research career in molecular epidemiology studying genetic susceptibility to cancer. David J. Hunter, MBBS, MPH, ScD, has extensive experience in chronic disease and molecular epidemiology. He has mentored numerous graduate students and postdoctoral fellows; two graduate students he co- supervised are now postdoctoral fellows in the NCI Genetic Epidemiology Program. He is a co-investigator of the Nurses' Health Study I and Health Professionals Follow-Up Study based at Harvard. Dr. Hunter is familiar with the research methods proposed in this project and he will oversee Dr. Chen's research activities and education. Dr. Chen proposes to use the resources of three large well-characterized cohort studies (the Nurses' Health Study I, the Health Professionals Follow-Up Study, and the Physicians Health Study) to prospectively assess gene-nutrient and other gene-environment interactions in the etiology of colorectal adenoma and carcinoma. Specifically, she will assess whether polymorphisms in the alcohol dehydrogenase type 3 (ADH3), cytochrome P450IIE1 (CYP2E1), and methylenetetrahydrofolate reductase (MTHFR) genes are associated with these cancers and whether they modify associations with intake of folate, methionine and alcohol, as well as other potentially carcinogenic or anticarcinogenic nutrients on risk of colon cancer and polyps. In addition, she will modify the existing PCR- RFLP based genotyping methods and adapt more flexible and efficient technologies while maintaining high accuracy. The proposed study would be valuable as positive associations would clearly implicate the substrates of the gene product as environmental carcinogenic exposures, clarifying colon cancer etiology and pointing to preventive dietary and other lifestyle modifications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: GENES, ANTICARINOGENS AND COLON NEOPLASMS Principal Investigator & Institution: Lin, Henry J.; Professor; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, CA 90502 Timing: Fiscal Year 2001; Project Start 30-SEP-1996; Project End 31-JUL-2006 Summary: (provided by applicant): The long-term goal is to use genetics and epidemiology to identify targets for prevention of colon cancer. The application is on prostaglandin biosynthesis as a promising target, because aspirin prevents some cases of colon cancer. The hypothesis is that genetic variation in prostaglandin production may mimic aspirin effects and shed light on preventive mechanisms. Work will focus on naturally-occurring mutations in people and targeted mutations in mice in a nuclear prostaglandin pathway defined by: cytosolic phospholipase A prostaglandin H synthase 2 (PTGS2/Cox-2), hematopoietic prostaglandin D synthase (H-PGDS), and peroxisome proliferator-activated receptor gamma. The project builds on discovery among 10 percent of African Americans of a PTGS2/Cox-2 mutation (Val5llAla) near the active site of the enzyme. Specific aims are to: (1) conduct case-control analyses on prevalence of colorectal adenomas and cancer in relation to genetic variants in PTGS2/Cox-2 and H-PGDS; (2) assess human interindividual variation in PTGS2/Cox-2 activity in relation to the Va151 1 Ala enzyme variant; (3) develop in vitro expression assays for novel variants identified in H-PGDS; and (4) develop a knockout mouse model of variation in H-Pgds to complement human epidemiologic studies. Three case-control studies will be used to assess effects of genetic variation on colon neoplasms: a Kaiser sigmoidoscopy study of adenomas (1,700 subjects); a Univ. of North Carolina colonoscopy study of adenomas (800 subjects); and African American cancer cases and controls (roughly 400) from the Multiethnic Cohort Study. Results may lead to better understanding of protective mechanisms involving aspirin and nonsteroidal anti-inflammatory drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC ALTERATIONS OF P53R2 AND COLORECTAL ADENOMA Principal Investigator & Institution: Xie, Dawen; Epidemiology and Biostatistics; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, SC 29208 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Colorectal cancer is the second most common cause of cancer mortality in the United States. The maintenance of genomic integrity after DNA damage depends on the coordinated action of cell cycle checkpoint controls and DNA damage repair systems. Molecular biological studies have clearly indicated that colon cancer is a disease caused by an accumulation of multiple genetic defects. One of the most studied genetic defects has involved the p53 gene. It is the major target for genetic alterations or biochemical activations in human cancer. However, the mechanism by which p53 exerts its effects or alters other signaling systems is largely unknown. In recent years a number of specific p53 target genes have been discovered and are likely to be involved in downstream target effects of altered p53 protein including cell cycle arrest, apoptosis, and tumor suppression. Recently, an important p53 downstream target gene, p53-inducible ribonucleotide reductase small subunit 2 (p53R2) was identified in a colon cancer cell line. p53R2 is a gene that is essential for DNA repair, and loss of function of this gene results in dysfunctional repair mechanisms. The p53R2 gene is mutated in either the regulatory region or the coding region. In preliminary work we have identified several germline mutations/polymorphisms in the first intron (the regulatory region of p53R2) in six of twenty patients with incident colorectal adenomas. We hypothesize that germline mutations/polymorphisms of p53R2 result in differential susceptibility to colorectal neoplasia. We propose to 1) determine distributions and frequencies of germline mutations/polymorphisms of p53R2 in participants in a recently concluded community, colonoscopy-based case-control study of incident sporadic colorectal adenoma (n=174 cases and 226 controls); 2) investigate associations of these mutations/polymorphisms with risk for adenoma; 3) identify the precise mutation(s)/polymorphism(s) in the p53R2 gene responsible for altered DNA repair system mechanisms; and 4) conduct preliminary work on the functional significance of genetic variants in the regulatory region of p53R2. This project will provide insight and preliminary data for further study of a novel downstream target gene of p53 signaling that ultimately may be responsible for dysfunctional DNA repair, thus contributing to greater vulnerability for developing colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC DETERMINATES OF HUMAN COLON NEOPLASIA Principal Investigator & Institution: Wiesner, Georgia L.; Assistant Professor; Genetics; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-JUN-2004 Summary: Dr. Georgia Wiesner is a junior faculty member in the Department of Genetics at Case Western Reserve University (CWRU) who is uniquely qualified for a K23 career development award. She has dual training in Medical Genetics and Internal Medicine and has a long term goal of conducting patient-oriented research in cancer susceptibility. Dr. Wiesner is currently the principal Geneticist on a research project with her mentor, Dr. Sanford Markowitz, which is aimed at establishing a patient-based family resource of kindreds with colon cancer and colon adenomatous polyps in order to identify new genes that cause colon neoplasia. Along with Dr. Robert Elston, comentor, Dr. Markowitz and his group will provide an outstanding research and
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educational environment that will allow Dr. Wiesner to advance toward her goal of independent translational research in genetics and molecular biology. The long range objectives of this proposal are to identify the gene or genes in the American population that cause susceptibility for colon cancer or colon adenomatous polyps. This will be done using the affected sibling pair methodology on a unique cohort of kindreds that Dr. Wiesner is currently establishing at CWRU. These families have at least one pair of siblings who have both been diagnosed with colon cancer and/or adenomatous polyps. The notion that certain genetic loci are linked to the development of colon neoplasms is a central concept of carcinogenesis and there is compelling evidence that a significant fraction of common forms of colon cancer are caused by unknown genes that increase an individuals life-time risk for colon cancer development. The specific aims of the proposal are: 1. To ascertain and collect DNA from 300 sibling pairs who are both affected with colon cancer and/or adenomatous polyps. 2. To identify, and exclude from linkage analysis, kindreds with known syndromes that have been linked to early onset forms of inherited colon cancer. 3. To test whether neoplasia in the study analysis population of affected sibling pairs demonstrates linkage to any of the candidate gene loci APC, COX2, sPLA2, and DNMT, or NAT1/2 for which colon neoplasia susceptibility variants have been identified in murine models or in restricted human populations and 4. To employ a set of 350 polymorphic markers to conduct a complete scan of the genome to identify new genes that are associated with susceptibility for cancer or colon polyps in these sibships. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: GENETIC EPIDEMIOLOGIC STUDIES OF POLYPS AND CANCER Principal Investigator & Institution: Potter, John D.; Member & Program Head; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, WA 98109 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 31-AUG-2004 Summary: (Adapted from applicant's abstract): The etiology of colorectal cancer and polyps involves genetic as well as environmental factors. The colon is exposed to a large number of genotoxic compounds both from exogamous and endogamous sources. Hereditary non-polyposis colorectal cancer illustrates the importance of DNA repair mechanisms in colorectal carcinogenesis. We hypothesize that polymorphisms in common DNA repair enzymes may also affect the risk of colorectal neoplasia. In the first 4 years of this grant, we have measured several polymorphic enzymes a) related to the metabolism of specific carcinogens from diet and tobacco smoke and b) in the folate pathway. Polymorphisms in other enzymes related to alcohol metabolism (also a source of DNA damage) and rotate metabolism linked to DNA repair via the provision of nucleotides) may also modulate risk. The goals of this competing renewal are to investigate the risk of colon cancer, colorectal adenoma, and colorectal hyperplastic polyps associated with 1) polymorphisms in DNA repair enzymes, specifically in hMLHI, hMSH2, MSH6, hOGGI, XRCC1, XRCC3, XPD, and AGT; 2) polymorphisms related to alcohol metabolism, specifically alcohol dehydrogenases 2,3, and 4; and 3) polymorphisms in enzymes in folate metabolism, specifically in MTHFR, thymidylate synthase (TS), and methionine synthase. We further plan to investigate possible interactions in determining risk of colorectal neoplasia: 1) between relevant environmental exposures and genetic polymorphisms (e.g., dietary intakes of folate and TS polymorphisms; cooked meat and nucleotide-excision repair enzymes); and 2) between polymorphisms in DNA repair genes and those in folate, or alcohol-related enzymes. Two large completed case-control studies of colorectal polyps (adenoma n=550 cases, n=700 controls, and hyperplastic polyps, n=200 cases) and colon cancer
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(n=1650 cases, n=1950 controls) - with extensive data on diet, alcohol intake, smoking history, and family history, as well as genotype information on other relevant genes will provide the basis for this study. Information on a number of DNA damage-repair pathway polymorphisms and their interactions with relevant exposures will help build our understanding of the molecular mechanisms involved in the stages of colorectal neoplasia; ultimately, the findings should provide directions for future screening and prevention strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: GENOMIC MARKERS OF COLON CANCER PROGRESSION Principal Investigator & Institution: Waldman, Frederic M.; Professor; Cancer Center; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (Provided by applicant) The goal of this Project is to identify and validate tumor markers which are associated with aggressive tumor behavior, and which predict the outcome of patients with colon cancer. DNA copy number alterations will be identified at megabase resolution using high throughput array-based CGH. Alterations will be identified based on associations with clinical outcome. Multiple sets of tumors will be used to identify genomic regions whose alteration is associated with outcome: fresh tumors from the UCSF and CHTN tissue banks (a pilot set to refine the arrays used in the remaining studies), archival untreated node negative tumors from UCSF, archival treated node positive tumors from UCSF, and tumors from three separate national clinical trials. We will test whether the same genomic alterations are predictive of outcome in each of these groups. A total of over 1200 tumors will be characterized for genomic alterations in this study, a number providing sufficient power to detect differences in risk to allow patients and physicians to make clinical decisions about therapy. CGH arrays will be applied to tumor material from patients who have been treated on homogeneous clinical trials. These studies will take advantage of ongoing correlative science studies which are associated with three separate treatment trials. 1) Candidate markers will be tested for predictive utility by DNA array analysis in a set of 300 stage III tumors receiving adjuvant chemotherapy (CALGB 9865/8896). Outcome for these cases is already known, and the status of microsatellite instability has been defined, 2) Candidate prognostic genomic markers will be detected by DNA array analysis in a set of 300 Stage IIcolon cancers undergoing surgical resection alone (CALGB 9581).These cases are currently being accrued, and phenotypic markers are being assessed. 3) Candidate predictive genomic markers will be detected by DNA array analysis in a set of 300 Stage III colon cancers undergoing surgical resection and one of two adjuvant therapies (CALGB 89803). These cases are also being accrued, and phenotypic markers assessed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HEALTH COMMUNICATION IN CANCER CONTROL Principal Investigator & Institution: Campbell, Marci K.; Associate Professor; Nutrition; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001; Project Start 27-SEP-1999; Project End 30-APR-2003 Summary: The objective of the proposed study is to develop and evaluate innovative health communication interventions aimed at colorectal cancer prevention in a population based sample of North Carolina residents. The goals of the intervention are
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to: 1) increase mean daily servings of fruits and vegetables consumed; 2) increase mean frequency and metabolic expenditure (METS) of regular physical activity: and 3) increase the percentage of participants who obtain recommended colorectal cancer screening tests. The study will test the effectiveness and cost-effectiveness of two different intervention approaches: Tailored Printed Communications (TPC) and Tailored Motivational Interviews (TMI). The TPC component will include development and provision of four individually tailored bulletins that focus on the main health behaviors targeted for intervention (increasing fruits and vegetables, physical Activity, and colorectal cancer screening). The TMI component will include conducting four telephone-based motivational interviews focused on improving the same behaviors. The target population will be a randomly recruited population-based sample of North Carolina residents from 33 counties; including an equal number of participants with and without a history of colon cancer. This study's recruitment will be from the same population-based sample that is participating in the North Carolina Colon Cancer Study (NCCCS). A total of approximately 800 people will be recruited to participate. The study will use a factorial research design to test the relative impact of each intervention. We will use a stratified random assignment method (stratification by case/control status and by race), to ensure balance among conditions. Participants will be randomly assigned to one of four conditions: TPC Intervention, TMI Intervention, COMBINED (TPC and TMI), and CONTROL (receives generic materials not related to study objectives). This design will allow testing of the main effects of each intervention component as well as possible interaction effects between the components. Data will be collected from study participants at baseline prior to the start of interventions, and at 12 month follow-up. Survey data will be collected by trained staff using telephoneadministered surveys. Data from the NCCCS surveys, which include detailed dietary, physical activity, health, and screening questions, will also be compared at baseline. Blood samples will be collected at baseline as part of the NCCCS study, and at follow-up to measure biomarkers associated with fruit and vegetable consumption. Cost data for the development and delivery of each intervention will be systematically collected. Process data will measure receipt, recall, and acceptability of each intervention. Primary analyses will focus on change in the targeted behaviors comparing experimental and control groups. Separate analyses will evaluate changes among those who have had colon cancer compared to those without the disease. Differences in effects by characteristics such as race, gender, education, and income will also be explored. Cost effectiveness analysis will provide population-based estimates associated with delivering these interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: HEREDITARY BREAST CANCER--GENETIC AND MOLECULAR STUDIES Principal Investigator & Institution: Anton-Culver, Hoda A.; Professor and Chief; Medicine; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2001; Project Start 04-FEB-1994; Project End 31-JUL-2003 Summary: A major risk factor for breast cancer is family history of the disease. Original estimates suggested that 50 percent of the cases of familial breast cancer have BRCAI and/or BRCM mutations. Further, the majority of families with breast and ovarian cancer have mutations in BRCAI. However, the frequency of BRCA mutations is not fully understood in families with a modest cancer phenotype or where other tumors occur in combination with breast. In particular Familial breast and ovarian cancer, familial breast and colon cancer and familial breast and prostate cancer are three
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combinations where each is known own to share common risk factors, moleculargenetic predisposition and/or shared etiologic biological plausibility. This is an application for renewal of our existing NCI project of the same name (1, U0l CA5886004), converted from an R01 as of January 1997. To date, our current project includes population based breast (1270) and ovarian (262) cancer probands. Pedigree data on first- and second-degree relatives and first-cousins, pathology data, clinical information, epidemiologic risk and diet data, blood and tissue specimens and laboratory results are available on all probands. There will be no further ascertainment of new probands in this proposed project. The overall goal of this project is to maintain and follow up the existing family resource, further characterize BRCA mutations in breast and ovarian cancer families and explore the associated functions of BRCA1 missense mutations. In addition, we will determine whether there is molecular genetic evidence for the aggregation of breast and colorectal cancer in a subgroup of the existing high risk breast cancer families. There is strong Familial and molecular genetic evidence of an association between breast and ovarian cancer and also a familial association between breast and colon cancer. Further, we have preliminary results that show mutations in MSH2 and MLH1 in breast cancer families where there is colon cancer in first or second degree relatives. It is important, therefore, that candidate genes (such as mismatch repair genes) relevant to the tumor spectrum in these families in addition to BRCA1 and BRCA2 be examined and possible new genetic alterations be explored. The data generated from the proposed study will have future clinical applications particularly for subjects from breast cancer families, possessing the diverse spectrum of tumors as is often observed in familial breast cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: HETEROGENEITY OF HUMAN COLON CARCINOMA Principal Investigator & Institution: Brattain, Michael G.; Professor and Chairman; Roswell Park Cancer Institute Corp Buffalo, NY 14263 Timing: Fiscal Year 2002; Project Start 01-FEB-1982; Project End 30-JUN-2007 Summary: This is a competitive renewal for a project that has been directed at understanding the role of aberrant TGFalpha signaling as a basis for disrupted growth regulation in colon cancer. We have found that TGFalpha is constitutively upregulated in highly malignant colon cancer cells, but is downregulated in Go premalignant and normal cells. This constitutive TGFalpha expression leads to a low, but constitutive activation of the EGFR, ErbB2 and downstream signaling including the PLCgamma, MAPK and PI3K pathways. These pathways generate growth factor independence as reflected by lack of exogenous growth factors for cell cycle re-entry and constitutive cell survival signaling. Colon cancer is one of the histological types of cancer showing a low rate of response to EGFR antagonism in the clinic as several small molecular weight tyrphostin derivatives as well as monoclonal antibodies are in various stages of development. The small molecular weight EGFR antagonists appear to be pan ErbB antagonists as well, but we have found that they fail to inhibit autophosphorylation of Y1248 by activated ErbB2 kinase in EGFR/ErbB2 heteromers. This is important because ErbB2 kinase, EGFR kinase independent signaling is prevalent in colon cancer cells and can lead to the activation of the PI3K or PLCgamma pathways and cell survival signaling. Thus, we have identified novel mechanisms of ErbB2 mediated signal diversification arising from aberrant autocrine TGFalpha which can circumvent the effects of this class of compounds in the clinic. Consequently, it is important to understand this signal diversification in colon cancer in order to optimize combination therapy with EGFR and ErbB2 antagonists. Specific Aims for the next cycle of the project
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are: 1. Determine the role of ErbB2 in the specification of essential signaling contributing to the malignant phenotype in colon cancer cells. 2. Determine how repression of ErbB2 dependent kinase signaling affects therapy by EGFR antagonists. 3. Determine mediators of cell survival signaling by ErbB family autocrine activation in colon carcinoma cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: HIGH RISK FAMILIAL COLON CANCER- GENETICS AND PHENOTYPE Principal Investigator & Institution: Burt, Randall W.; Senior Director for Prevention and Outre; Huntsman Cancer Institute; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2003; Project Start 01-SEP-1985; Project End 29-FEB-2008 Summary: (provided by applicant): Genetic, clinical and molecular characterization of inherited colon cancer risk is the focus of our present and long-term work. Genes for the rare syndromes of this malignancy have been found but account for only a small fraction of the estimated one-third of colon cancer cases that arise from inheritance. The aims of our present proposal are 1) to identify the susceptibility genes that give rise to the more common inherited risk, 2) to continue to define the associated phenotype, 3) to establish molecular characteristics of the high-risk families and known syndromes with gene expression profiling and 4) to examine the expression of specific APC/beta-catenin pathway genes as potential diagnostic markers. Together these goals will provide tools to identify persons with inherited risk. We will accomplish the aims as follows: We will identify colon cancer susceptibility loci by linkage analysis of large high-risk colon cancer families in which the known syndromes of colon cancer have been ruled out. Colonoscopy is performed on family members to define polyp expression, both for phenotype and linkage analysis. Gene expression profiling by microarray analysis is performed on normal appearing and neoplastic colonic tissue obtained at colonoscopy and immediately preserved. Profiling will assist both in identification of susceptibility pathways and in establishing characteristic expression profiles in the inherited colon cancer settings. Gene expression patterns will be examined in the normal and neoplastic tissue of the high-risk families and compared to similar samples from families with familial adenomatous polyposis (FAP), attenuated FAP, hereditary nonpolyposis colorectal cancer, sporadic adenomatous polyp cases and normal controls. Gene expression will be examined using a reference RNA and analyzed by supervised (and later unsupervised) analysis of the groups. Finally the expression of four specific APC/beta-catenin pathway marker genes will be examined in neoplastic and normal tissues from the above groups by both real-time quantitative PCR and by in situ RNA hybridization. Previous microarray experiments in our laboratory indicate that expression of these genes is frequently perturbed in sporadic polyps, making them attractive markers of cancer susceptibility to evaluate APC/beta-catenin pathway contributions in undefined forms of inherited colon cancer, as compared to defined inherited syndromes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HMG COA REDUCTASE AND COX2 INHIBITORS IN COLON CANCER Principal Investigator & Institution: Rao, Chintalapally V.; Scientist, Head, Associate Cchief; Institute for Cancer Prevention 1 Dana Rd Valhalla, NY 10595
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Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The overall objective of this proposal is to determine the chemopreventive efficacy of a combination of lovastatin (3-hydroxy-3methylglutaryl CoA reductase (HMG-R) inhibitor and celecoxib (COX-2-selective inhibitor) against colon cancer and to gain an understanding of the mechanism(s) of tumor inhibition by these agents. Colorectal cancer is one of the most common human malignancies in the United States, anticipated to account for 137,000 new cases and about 56,000 deaths in the year 2001. Developing chemopreventive agent(s) that aim to suppress tumor cell growth, but not normal cell growth, by targeting specific genes/factors that are responsible for tumor growth provides a rational approach. Our studies and those of others indicate that COX-2 and HMG-R activities were upregulated several-fold in colon tumors compared to normal mucosa and, importantly, the metabolites/molecules derived from these enzymes play a pivotal role in modulation of apoptosis and proliferation. Recent evidence from clinical trials, and in vivo and in vitro laboratory studies suggest that application of a combination of HMG-R inhibitors (cholesterol-lowering drugs) and COX-inhibitors (nonsteroidal antiinflammatory drugs) produces synergistic colon cancer-inhibiting effects. Thus, it is important to systematically develop HMG-R inhibitors and their combination with COX-2 inhibitors for colon cancer prevention and delineate the specific mechanisms that lead to modulation of apoptosis and proliferation by these agents. Specifically, we will examine 1) the chemopreventive efficacy of lovastatin on azoxymethane (AOM)induced colon carcinogenesis in rats (maximum tolerated dose selection; dose-response effects; and effectiveness during promotion/progression stages, 2) study the synergistic effects of lovastatin and celecoxib on AOM-induced colon carcinogenesis and assess effectiveness of these agents in combination on the promotion/progression stages, and 3) elucidate mechanisms by determining the effect(s) of lovastatin with or without combination of celecoxib on HMG-CoA reductase, FPTase, GGPTase, p53, p21CIP/WAF1, caspase-3 &- 6, Bax, Bcl-2, Fas and lamin B, COX-2, PPAR-y, p53, and prostaglandins levels. Finally, we will study the effects of these agents on cell proliferation, and apoptosis during different stages of colon carcinogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: HUMAN ABERRANT CRYPT FOCI--BIOMARKERS FOR COLON CANCER Principal Investigator & Institution: Pretlow, Theresa P.; Associate Professor; Pathology; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001; Project Start 09-FEB-1996; Project End 30-NOV-2005 Summary: Colorectal cancer is the second most common cause of cancer deaths in the US. A better understanding of its pathogenesis might lead to earlier diagnosis and/or prevention of this disease. Aberrant crypt foci (ACF) are the earliest identified neoplastic lesions in the colon. They are identified microscopically in whole-mount specimens of colon and recently have been identified in vivo in humans by endoscopy. Our hypothesis is that at least some of these benign neoplasms progress to malignant colon cancer. If we knew what alternation(s) in a normal colonic epithelial cell cause it to become neoplastic and/or what characteristics in ACF promote these benign neoplasms to become malignant, a greater number of colon cancers might be prevented. The APC/beta catenin pathway appears to play a key role in colon tumorigenesis. Its role in the formation and/or promotion of ACF will be examined by looking at the expression of several proteins in the APC/beta catenin pathway in serial histological sections of ACF that have been characterized for dysplasia. In adjacent sections, the expression of
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cyclooxygenase-2 will be evaluated. Chromosomal instability (CIN) appears to be a major player in 85 percent of sporadic colon cancers. Comparative genomic hybridization (CGH) will be used to evaluate if chromosomal instability is evident in ACF and what the earliest changes are. Fluorescence in situ hybridization (FISH) will be used on ACF to confirm the findings of CGF, to extend those findings to a larger number of ACF, and/or to detect gains or losses of chromosomal segments that have been reported in adenomas. Chromosomal instability also will be evaluated in ACF by looking for loss of heterozygosity (LOH) at several chromosomal locations. Primers for several microsatellite markers will be used with the polymerase chain reaction (PCR) to amplified DNA from microdissected ACF. Correlation of these multiple studies on the same ACF should provide new insights into the role of ACF in colon tumorigenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: HUMAN RNA BINDING PROTEIN AS A CANCER MARKER Principal Investigator & Institution: Ross, Jeffrey; Professor and Chair; Oncology; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2004 Summary: (provided by applicant): The goal of this proposal is to determine if a recently discovered RNA-binding protein is expressed specifically in human cancer tissue. The protein binds to a segment of the c-myc mRNA coding region that causes the mRNA to be unstable. This segment is called the Coding Region instability Determinant or CRD. The protein that binds to the CRD is the CRD-Binding Protein or CRD-BP. We discovered the CRD-BP using a cell-free mRNA decay system. We observed that polysome-associated c-myc mRNA was specifically and rapidly degraded by an endonuclease when competitor RNA corresponding to the c-myc CRD was added to the reactions. Cleavage occurred within the CRD of the mRNA. We reasoned that a protein might be shielding the CRD from endonuclease attack and that competitor CRD RNA was titrating the protein off of the mRNA. This protein, the CRD-BP, was later purified, sequenced, and cloned in our laboratory. Four subsequent observations from our lab revealed strong links between the CRD-BP and human cancer. Two findings suggest that the CRD-BP is an oncofetal protein: (i) The CRD-BP is expressed abundantly in fetuses but not in adults. (ii) The CRD-BP is expressed in most transformed human tissue culture cells. Two other findings suggest that the CRD-BP is a potential human tumor marker: (iii) The CRD-BP gene is amplified in approximately one-third of human breast cancer cases. (iv) The CRD-BP is expressed in some cases of human colon cancer but not in normal colon. Our working hypotheses are that (i) the CRD-BP is overexpressed in some or many human carcinomas and (ii) the CRD-BP might therefore be a new cancer marker. The following aims/questions explore these hypotheses: Aim I. The CRD-BP is overexpressed in colon cancer. Is it also overexpressed in lung, breast, and prostate cancers? The CRD-BP gene is amplified in breast cancer. Is it also amplified in colon, lung, and prostate cancers? If so, does CRD-BP gene amplification correlate with CRD-BP overexpression? Aim II. Do patients with colon, lung, breast, and prostate cancer make antibodies to the CRD-BP? Aim III. Is the CRD-BP itself detectable in serum from patients with colon, lung, breast, and prostate cancer? Aim IV. Does CRD-BP expression in these cancers correlate with cancer grade or with a poorer prognosis? These studies could provide clinicians with a novel tumor marker. They might also stimulate future studies to evaluate the CRD-BP as a therapeutic target. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IGFS DIFFERENTIATION
&
IGF-BINDING
PROTEINS
IN
GROWTH
&
Principal Investigator & Institution: Singh, Pomila; Professor; Anatomy and Neurosciences; University of Texas Medical Br Galveston 301 University Blvd Galveston, TX 77555 Timing: Fiscal Year 2001; Project Start 04-JAN-1995; Project End 31-JAN-2003 Summary: Role of IGFs in the transformation of several cancer cells is by now well established. Both IGFs (IGF-I and IGF-II) are potent mitogenic agents for several normal and neoplastic cells. IGF binding proteins (IGF-BPs), on the other hand are believed to modulate the mitogenic effects of IGFs. Within the past two years we and others have established that primary human colon cancers and established colon cancer cell lines express and secrete the mitogen, IGF-II, and the modulating proteins, IGF-BPs. It is, however, not known if IGFs and IGF-BPs play a major role in the growth and differentiation of colon cancer cells. It is speculated that the mitogenic potential of a colon cancer cell line will depend upon the relative expression of the mitogen and the modulator. The major hypothesis of this grant proposal therefore is that the relative expression and secretion of IGF-II and IGF-BPs dictates the growth differentiation potential of colon cancer cells. Our major strategy is to investigate the individual role of IGF-II and IGF-BPs in the growth and differentiation of colon cancers. Towards this goal we will use stable and inducible transfectants that either express the sense or the antisense form of the mitogen/modulatory proteins to confirm the relative role of IGFs and IGF-BPs in initiating or supporting the proliferative/differentiated state of the cells. Alternatively, we will measure the effect of IGF peptides, specific antibodies and antisense oligonucleotides on proliferation of a representative colon cancer cell line (Colo-205) (that does not differentiate in culture), and differentiation of a representative colon cancer cell line (CaCo2 cells) (that spontaneously differentiates in culture). In a second set of studies, the proliferation of colon cancer cells will be measured in vivo in specific mouse models, in the presence or absence of IGFs, IGF-BPs and IGF-receptor antagonists. Alternatively, growth and differentiation of cancer cells, transfected with vectors expressing the sense or antisense IGFs and BPs, will be measured in nude mice. These studies will help us to define the role of circulating vs autocrine (endogenous) IGFs and IGF- BPs in the growth and differentiation of colon cancers in vivo. At the end of these studies we expect to have defined the mitogenic/differentiation potential of IGFs in the presence of modulating IGF-BPs. The results of these studies will help us to move a step closer towards our overall goal of understanding the role of the IGF system in the proliferation and differentiation of neoplastic colonic mucosal cells, and provide the basic information for developing more appropriate, clinically relevant, protocols. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: IN VIVO IMAGING OF FORMATION OF HEPATIC METASTASES Principal Investigator & Institution: Kruskal, Jonathan B.; Beth Israel Deaconess Medical Center St 1005 Boston, MA 02215 Timing: Fiscal Year 2001; Project Start 01-MAR-2001; Project End 31-JAN-2003 Summary: (Applicant's abstract): The goal of this project is to identify specific molecular steps that occur in vivo during establishment of colorectal cancer metastases to the liver. The proposed experimental approach will utilize intravital light and fluorescent video microscopy, a mouse xenograft model of human hepatic colorectal cancer metastases, fluorescent probes and two well-characterized colon cancer cell lines with high (CX1) and low (MIP-101) metastatic potential, and corresponding high and lack of expression
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of CEA, to visualize directly cell interactions during the development of liver metastases. Specific Aim 1 will document the initial in vivo sequence of interactions between circulating colon cancer cells and resident liver Kupffer cells in a live mouse model. These studies will compare the ability of highly (CX1) and poorly (MIP-101) metastatic human colon cancer cells to interact with and activate periportal Kupffer cells in vivo, and investigate whether pharmacological inhibition of Kupffer cells (with Gadolimium chloride) abrogates initiation of the metastatic cascade. Specific Aim 2 will document the in vivo location and sequence of cellular interactions from the onset of sinusoidal E-selectin expression to tumor cell adhesion, transmigration and colonization. These studies will document the sites and relative intensity of downstream sinusoidal and outflow venous endothelial cell E-selectin expression in vivo and correlate this with sites and the temporal sequence of tumor cell adherence, transmigration, and onset of metastatic tumor growth. Finally, since intravital microscopy is able to delineate in our tumor model the earliest onset of angiogenesis, we will correlate the onset of angiogenesis with tumor cell type and the timing and intensity of systemic macrophage recruitment. This project will allow identification of a series of in vivo steps that can be used to explore novel diagnostic and therapeutic probes in animal studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: IN VIVO MODULATION OF PROGRESSION IN COLON CANCER Principal Investigator & Institution: Willson, James K.; Director, Ireland Cancer Center; None; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001; Project Start 06-SEP-1995; Project End 31-JUL-2003 Summary: (Applicant's Abstract) Employing unique cell and xenograft models, pathological alterations in growth factor responses were demonstrated to play key roles in colon cancer progression. Using a tetracycline repressible expression system in colon cancer xenograft models, loss of TGF beta signaling was linked to colon cancer progression and restoration of TGF beta signaling reversed tumorigenicity. In a second line of investigation, ectopic expression of TGF alpha resulted in accelerated tumor growth and tetracycline mediated reversal of this ectopic expression caused tumors to regress. At the inception of the studies, it was anticipated that the primary consequence of disrupted growth factor signaling in these colon cancer xenograft models would be a direct alteration in growth regulation at the cell cycle level. Unexpectedly, the results suggest that the altered tumor growth was largely due to modulation of extracellular components of the xenograft such as integrin expression or angiogenesis and that these changes in turn appear to have dramatic effects on in vivo tumor cell proliferation or apoptosis. These results suggest that tumor progression involves autocrine growth factor controlled interactions of malignant cells with the tumor microenvironment to prevent or treat colon cancers. To examine the role of candidate autocrine activities in human colon cancer progression, in vivo models which will confirm the dependency of tumor growth on these autocrine activities by modulating downstream effectors of their action are planned. Candidate molecular targets will be modulated in vivo using tetracycline controllable systems. A central issue which the applicant will examine is the relationship of tumor stage on the impact of growth factor modulation. For the purposes of these studies, he plans to evaluate xenograft tumors at two different stages, the dormant phase or pre-angiogenic phase of growth and the growth phase or post "angiogenic switch" phase. By linking the expression of a specific molecular mechanism (e.g. elevated angiogenesis due to malignant cell VEGF expression) to a tetracycline responsive promotor, he can examine the impact of modulating that mechanism in vivo at these two stages of xenograft tumor progression. The ultimate goal of this proposed
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investigation is to use the unique human colon cancer xenograft models that will be developed to evaluate new pharmaceutical agents designed to target novel molecular mechanisms of tumor progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: INCREASING COLON CANCER SCREENING IN PRIMARY CARE Principal Investigator & Institution: Myers, Ronald E.; Associate Professor; Medicine; Thomas Jefferson University Office of Research Administration Philadelphia, PA 191075587 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2005 Summary: ABSTRACT=The American Cancer Society recommends that men and women 50 or more years of age have a annual fecal occult blood test (FOBT) and a flexible sigmoidoscopy (FS) examination every five years to screen for colorectal cancer (CRC). Alternative CRC screening regimens that are recommended include having a barium enema X-ray (BE) at five- year intervals or a colonoscopy (CX) every 10 years. Compliance with CRC screening guidelines is low. The proposed study, Increasing Colon Cancer Screening in Primary Care, is intended to develop and test methods that may be used to increase CRC screening compliance. Study participants will be male and female patients of a large, urban primary care practice (Jefferson Family Medicine Associates), who are 50 to 74 years of age and are at average risk for CRC according to American Cancer Society guidelines. After a Baseline Survey and Baseline Chart Audit are completed, 1,488 study participants will be randomly assigned either to a Control Group, a Standard Intervention (SI) Group, a Tailored Intervention (TI) Group, or a Tailored Intervention plus Phone (TIP) Group. During a two-year period, the Control Group will receive usual care, while the intervention groups will be provided two annual screening interventions. The SI Group will receive a standard CRC screening invitation letter, a CRC screening kit (an educational booklet, and an educational videotape, and FOBTs), and a standard reminder letter. The TI Group will receive a tailored CRC screening invitation letter, a CRC screening kit, and a tailored reminder letter. Here, educational messages tailored to participant stage of decision making about screening will be embedded in the letters. The TIP Group will receive the same intervention at the TI Group, plus a tailored telephone counseling call to amplify educational messages in the tailored screening invitation letter. Midpoint and Endpoint Surveys will be administered and an Endpoint Chart Audit will be completed for study (participants. Specific aims of the study include the following: (1) Assess the impact of study interventions on screening compliance. (2) Assess the impact of study interventions on screening decision-making stage. (3) Assess the impact of study interventions on defined cognitive and psychosocial variables. (4) Identify variables associated with screening compliance and decision-making stage. (5) Evaluate intervention cost- effectiveness relative to screening compliance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INSULIN RESISTANCE AND COLON CANCER IN BLACKS AND WHITES Principal Investigator & Institution: Keku, Temitope O.; Associate Professor; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2002; Project Start 17-SEP-2002; Project End 31-JUL-2006
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Summary: (provided by applicant): The long-term goals of this project are to define the interactions between insulin resistance, genetic and environmental risk factors in the etiology of colon cancer and to achieve further career development training for the applicant in molecular epidemiology and bioinformatics. Dr. Keku, the applicant, is an Assistant Professor at UNC. Her mentors are Drs. Robert Millikan and Kay Lund. Dr. Millikan is an established molecular epidemiologist. He is the Principal Investigator of the Carolina Breast Cancer Study and also part of an international collaboration investigating the interactions between sunlight and genetic factors in the etiology of malignant melanoma. Dr. Lund is a Professor of Molecular Biology and Physiology and an expert on the IGF system as it relates to GI disease. They propose a mentored career training for Dr. Keku in molecular epidemiology and bioinformatics utilizing the resources at the UNC School of Public Health and the Department of Cell and Molecular Physiology in the School of Medicine. The study proposed as part of the mentored career development training is a case-control study of insulin resistance (insulin/IGF) and colon cancer in African Americans and whites. Colon cancer is the most common gastrointestinal malignancy in the United States. The rise in the incidence and mortality of colon cancer in African Americans poses a serious public health problem. The specific aims of this study are: 1)To examine the association between insulin/IGF axis and colon cancer in African American and white subjects with and without colon cancer. 2) To evaluate the role of genetic polymorphisms in the insulin/IGF axis and their relationship to colon cancer and associated risk factors. 3) To examine the association between the insulin/IGF-axis and factors related to insulin resistance in African American and white subjects with and without colon cancer. The proposed study will utilize available specimens and measurements from a population based case-control study of colon cancer (NCI R01 CA66635). We will use plasma and DNA specimens to determine insulin, IGF-I, IGF-II, IGFBP-1, IGFBP-3, glucose and C-peptide levels and for genotyping assays respectively. The results of the laboratory assays will be merged with lifestyle/dietary information and analyzed for associations. The proposed project will advance the understanding of the role of insulin resistance in colon cancer among African Americans and whites. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: INTEGRIN MODULATION OF PROLIFERATION IN COLON CANCER Principal Investigator & Institution: Kuwada, Scott K.; Internal Medicine; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2001; Project Start 10-JUL-1997; Project End 30-JUN-2003 Summary: Anchorage-independent growth is a hallmark of colon cancer cells in general. Growth factors and the extracellular matrix coordinated stimulate normal cell proliferation. This is mediated principally by growth factor receptors and integrin receptors whose signaling pathways converge at several levels within cells. Autocrine growth factor - EGFR loops are vital to the proliferation of many colon cancer cell lines. During colonic tumorigenesis, integrin expression is greatly diminished, and the specific loss of alpha 5/beta I integrin heterodimer expression has been observed in vivo. Transfection of alpha 5 integrin into malignant CHO cells devoid of alpha 5/beta I integrin expression abrogates the malignant phenotype and inhibits their proliferation. Thus, we hypothesize that transfection of alpha 5 integrin into colon cancer cell lines lacking alpha 5 integrin expression will decrease their growth by directly inhibiting the EGFR signal transduction pathway. The primary aims of this proposal are to demonstrate that alpha 5 integrin expression in colon cancer cells: reverses anchorage-
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independent growth; inhibits their proliferation by compartmentalizing, deactivating (decreased phosphorylation), or decreasing protein expression of EGFR signal transduction pathway kinases. The demonstration of a direct modulation of EGFRmediated cell growth by a single integrin would expand our knowledge of how colon cancer cells escape anchorage-dependent growth control, and might lead to novel therapeutic strategies for colon cancer based on growth regulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: INTERACTION CARCINOGENESIS
OF
APC
AND
P53
IN
COLORECTAL
Principal Investigator & Institution: Narayan, Satya; Shands Cancer Center; University of Florida Gainesville, FL 32611 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-JAN-2003 Summary: Colon cancer is the second most frequent cancer diagnosed in the United States, with an estimated 95,600 new cases and 47,700 deaths in the year 1998 (American Cancer Society - Cancer Facts and Figures; February 6, 1998). The association of altered expression of adenomatous polyposis coli (APC) tumor suppressor gene with poor prognosis in colon cancer patients is well established; however, little is known about APC's biological functions, and virtually nothing is known concerning the regulation of APC gene expression. The long-term goal of this project is to understand the mechanisms by which the APC gene is regulated, and the function of its product in normal and cancer cells. Development of colon cancer is a multistep process that frequently involves mutations in both the APC and p53 genes. Our preliminary results indicate that expression of APC mRNA is transcriptionally activated in a p53-dependent manner by the DNA-alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The objective of this study is to elucidate the mechanisms of p53-dependent transcriptional regulation of APC by agents that damage DNA. Based on our prior studies and the work of others, we propose that, in response to signals generated by genotoxic agents, levels of phosphorylated p53 protein increase and form transcriptionally active p53/TFIIH complex that enhance the rate of APC transcription, resulting in APC-mediated cell cycle arrest or apoptosis of colon cancer cells. This hypothesis will be tested by: 1) characterizing the assembly of the DNA damageinduced, p53-mediated transcriptional complex on the APC promoter and evaluating its functions by using a chloramphenicol acetyl transferase (CAT)-reporter expression; and 2) analyzing the mechanisms of APC gene regulation by p53 in an in vitro run-off transcription system. Our results are expected to establish a functional link between APC and p53, the two most frequently mutated tumor suppressor genes involved in cell cycle arrest and apoptosis in colon cancer. Therefore, novel therapeutic strategies may emerge with respect to potential new targets for chemotherapeutic intervention in colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: INTESTINAL CELL GROWTH CONTROL: ROLE OF TYROSINE KINASES Principal Investigator & Institution: Cartwright, Christine A.; Associate Professor; Medicine; Stanford University Stanford, CA 94305 Timing: Fiscal Year 2001; Project Start 15-JUN-1991; Project End 31-MAY-2006 Summary: (Adapted from the Applicant's Abstract): Colon cancer is the third leading cause of cancer deaths in the United States. This research focuses on the role of the Src
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tyrosine kinase in colonic carcinogenesis. Others and the PI have shown that downregulation of Src activity is important for differentiation and that upregulation of Src activity is important for malignant transformation of intestinal cells. Thus, the goal is to define molecular mechanisms that downregulate Src in normal colon and those that upregulate Src in colon cancer. The hypothesis is that specific domains of Src, and the proteins that bind to them, are important regulators of Src activity. Thus, effort is directed towards identifying cellular proteins that modulate Src function during intestinal cell maturation and malignant transformation. Using a yeast two-hybrid assay, the PI recently identified RACK1, a receptor for activated C kinase and a homolog of the beta subunit of G proteins, as a novel Src SH2-binding protein. The PI found that RACK1 inhibits the specific activity of Src and the growth of NIH 3T3 cells. RACK1 exerts its effect on cell growth, in part, by prolonging the G0/G1 phase of the cell cycle. The PI will further characterize Src's partner RACK1 and the mechanism by which RACK1 functions to regulate Src activity and intestinal cell growth. One aim is to assess the requirement of binding of the two proteins and of phosphorylation of RACK1, by Src for RACK1 inhibition of Src activity and cell growth. The second aim is to analyze the mechanism by which cross talk occurs between the RACK1-linked signaling pathways of Src and PKC. The third aim is to assess RACKl's influence on cell transformation by v-Src. The fourth aim is to further analyze the effect of RACK1 on the cell cycle and on Src activity during the cell cycle. These studies should generate significant new information regarding a novel inhibitor of Src and cell growth. Understanding how inhibitors of mitogenic signals work to regulate intestinal cell growth and how loss of that inhibition results in uncontrolled growth and malignant transformation, should impact our basic understanding colon cancer biology and lead to development of novel strategies for colon cancer therapy. Endogenous inhibitors of oncogenic kinases are potentially tumor suppressors; they represent exciting new targets for therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: LEF/TCF EXPRESSION IN COLON CANCER Principal Investigator & Institution: Waterman, Marian L.; Associate Professor; Microbiol & Molecular Genetics; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): Molecular genetic analysis of colon cancers has established that the Wnt signaling pathway is involved in early tumor development, particularly in colon cancer. The transcription factors that commute the signal into changes in target gene expression are members of the Lymphoid Enhancer Factor/T Cell Factor (LEF/TCF) family. The genes for two members of this family, TCF1 and LEF1, produce truncated dominant negative forms that limit Wnt signals and may function as growth suppressors. We have found that the LEF1 gene is ectopically induced in colon cancer, but only the full-length activating form is expressed - the dominant negative form is not. The patterns of LEF1 and TCF1 expression during colon cancer progression are not known. TCF1 is normally expressed in human colon, but the relative amounts of full-length and dominant negative forms in normal colon and cancer are also not known. Based on results from our preliminary studies, we propose that fulllength isoforms of LEF/TCFs predominate in colon cancer. Furthermore, we propose that the Wnt pathway itself plays a role in promoting expression of full-length isoforms. To test these hypotheses we will determine the expression of LEF1 and TCF1 isoforms in normal, polyp and colon carcinoma (Specific Aim 1). To probe the mechanism of
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aberrant LEF1 expression, the genetic integrity of the LEF1 gene and its sensitivity to epigenetic changes in chromatin structure will be assessed in colon cancer cell lines (Specific Aim 2). TCFl/a-catenin and TCF4/ a-catenin complexes can activate the LEF1 promoter in transient transfection assays, other LEF/TCFs cannot. We propose that LEF1 is a target of specific TCFl/4/ a-catenin complexes in cancer. Experiments are proposed to explore this regulation and test for its relevance to the endogenous LEF1 gene in colon cancer cells (Specific Aim 3). Based on the selective effect of TCFI/4 on the LEF1 promoter, we hypothesize that each LEF/TCF family member carries unique target gene specificities and that their expression in cancer imparts distinct effects. To test this hypothesis, two strategies will be used to disrupt LEF/TCF function in colon cancer cells. Effects will be assessed by global gene expression profiles and cell growth and viability assays (Specific Aim 4). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: LEF-1 PROMOTER REGULATION IN CANCER Principal Investigator & Institution: Jimenez, Judith; Microbiol & Molecular Genetics; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2002; Project Start 18-MAR-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Mutations that cause aberrant activation of the Wnt Signaling Pathway are found in early stages of tumor development in colon carcinoma. The downstream components of the pathway are transcription factors that belong to the LEF/TCF family, and the focus of our lab is to study the regulation of the LEF1 gene. Northern blot analysis demonstrates that there are 3 LEF1 messages (3.6kb, 3.0kb, and 2.2kb) expressed from the locus. Two different promoters generate the 3.6 and 2.2 kb mRNA messages and have been characterized. The promoter for the 3.6kb message is a target of the Wnt pathway and is aberrantly expressed in colon cancer cell lines. The 3.0kb message is also aberrantly expressed in cancer, but its origin is not known. The focus of this proposal is to test the hypothesis that a region in exon 1 of the LEF1 gene harbors a third promoter which directs expression of the third LEF1 message (3.0kb) (Aim 1). Because the 3.6 and 3.0 kb messages are expressed together in colon cancer cell lines, we hypothesize that they are coordinately regulated. Due to the identification of a region in promoters 1 and 3 in exon 1 that contains putative Wnt and TGFbeta-response elements, experiments will be carried out to test if these elements individually play a role in the regulation of one or both promoters (Aim 2). If this putative regulatory region affects promoter activity, we plan to determine whether the Wnt and TGFbeta pathways cooperate to activate or act antagonistically to negatively regulate promoter 1 and 3 (Aim 3). Mutations in the TGFbeta Pathway are late events in the development of tumorigenesis, therefore, we hypothesize that the aberrant expression of LEF1 in colon carcinomas may be due to mutations that activate the Wnt pathway and mutations that inactivate the TGFbeta pathway. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LIFESTYLE, INSULIN, IGF-I AND COLORECTAL CANCER Principal Investigator & Institution: Kaaks, Rudolf J.; Group Leader; World Hlth Org Intl Agcy Res on Cancer Int'l Agency for Res on Cancer Lyon, Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): A Western lifestyle, characterized by a low level of physical activity, and an energy-dense diet rich in easily digestible (refined) carbohydrates and fats, is associated with an increased risk of developing colon cancer.
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Etiologic models to explain this association have focused mostly on effects of diet on exposures of the colonic rnucosa to mutagenic or tumor-promoting compounds in the gut lumen. A limitation of these models is that they do not explain the inverse relation of risk with physical activity or the positive relation of risk with obesity. A more recent theory states that effects of a Western lifestyle on colon cancer risk may at least in part be mediated by alterations in the metabolism of insulin and insulin-like growth factors (IGFs). Insulin is a key hormone in the regulation of energy metabolism. It increases the bio-activity of IGF-I by enhancing its synthesis, and by down regulating several of its binding proteins (IGFBP-1 and -2). Insulin and IGF-I both stimulate anabolic (growth) processes, as a function of available energy and elementary substrates (e.g., amino acids). In excess, the anabolic signals by insulin or IGF-I can promote tumor development by inhibiting apoptosis, and by stimulating cell proliferation. Overeating and obesity tend to increase plasma insulin and bio-active IGF-I, whereas plasma insulin and total and bioavailable IGF-I are decreased by energy restriction, which protects against many forms of cancer in animal models. The specific aims of the present study are: [1] to examine whether increased (prediagnostic) serum levels of glycated hemoglobin (a marker for plasma glucose) and C-peptide (a marker for insulin levels), and low levels of IGFBP-1 and IGFBP-2, increase risk of colon cancer, and possibly rectal cancer; [2] to examine whether elevated IGF-I concentrations (absolute, or relative to its major plasmatic binding protein -- IGFBP-3) are increase risk of colon and rectal cancers; [3] to examine whether high dietary glycemic load increases colorectal cancer risk ; and [4] to describe relationships of diet (particularly glycemic load), anthropometric indices, and other lifestyle variables with each of the serum peptides. This study seeks to increase understanding of etiologic mechanisms relating over nutrition to colon cancer development, which will eventually allow the in formulation of more precise nutritional guidelines for efficient prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: NETWORK
LUNG/COLON
CANCER
OUTCOMES--CANCER
RESEARCH
Principal Investigator & Institution: Weeks, Jane C.; Assistant Professor; Dana-Farber Cancer Institute 44 Binney St Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 18-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): We will accrue all patients with newly diagnosed lung or colon cancer receiving their care in one of five geographically diverse sites in the Cancer Research Network, an NCI-funded research consortium of HMOs. Automated data for all patients (2,058 patients with lung cancer over the two year enrollment period, and 1,732 patients with colon cancer over the two year enrollment period) will be supplemented with data obtained from complete medical record review and patient surveys for a sample of 1,424 patients with newly diagnosed lung cancer and 1,222 patients with newly diagnosed colon cancer. We will oversample African-Americans, Asians and Pacific Islanders, as well as Medicaid recipients. In addition, we will assemble an inception cohort of patients with newly diagnosed metastatic recurrences of colorectal cancer during the two-year enrollment period (projected at approximately 300 patients) for comprehensive data collection. We propose to lead analyses of CanCORS-wide core data in order to (1) examine the effect of race and ethnicity on patterns of care, treatment choice, quality of life, symptom control, and satisfaction; (2) characterize the types of providers seen by patients and examine the associations between provider characteristics/attitudes and patterns of care and outcomes; (3) evaluate the relationship between the structure/function of cancer care in the health
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care delivery systems of participating patients and patient outcomes, including health status, patient satisfaction, and cost; and (4) generate estimates of utility weights and time- and out-of-pocket costs that are disease- and treatment-specific for use in future cost-effectiveness analyses. Finally, in a Special Research Study we will aggregate cost data for CRN CanCORS subjects in order to (1) determine cancer-attributable phasespecific and lifetime costs of care for colorectal and lung cancer; (2) determine the proportion of total cancer-attributable costs that are spent on initial therapy versus second- and third line therapies for each cancer, stratified by stage at diagnosis; and (3) determine the relationship between type of initial therapy and the subsequent lifetime cancer-attributable costs of care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: LYMPHATIC MAPPING AND SENTINEL NODE ANALYSIS Principal Investigator & Institution: Bilchik, Anton J.; John Wayne Cancer Institute 2200 Santa Monica Blvd Santa Monica, CA 90404 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Provided by applicant): Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. The five-year survival rate is high (90 percent) following treatment of American Joint Committee on Cancer (AJCC) stage I CRC but decreases substantially as disease progresses to stage II (75 percent) and stage III (50 percent). Hence, the presence of lymph node metastasis is one of the most important prognostic factors. Approximately one-third of patients initially diagnosed with AJCC stage I or II CRC develop systemic disease despite "negative" lymph nodes. This implies that these patients have occult nodal or systemic disease not detected by current techniques. Previous studies have demonstrated that lymph node micrometastases documented by ultrastaging correlate with poorer survival. Because the average CRC resection specimen contains 15 or more lymph nodes, the utilization of ultrastaging techniques on each lymph node would be labor and cost intensive. Therefore, a means of focusing an examination on the lymph nodes most likely to contain metastases would be advantageous. Our hypothesis is that inaccurate pathology analysis (i.e. the presence of occult metastasis in CRC regional lymph nodes) may account for the stage I or II patients that will develop systemic disease. To address this problem, improved methods for regional node sampling, pathology analysis, and metastatic disease detection are needed. JWCI developed the sentinel lymph node (SLN) technique to improve staging and reduce unnecessary lymph node dissections in patients with melanoma and breast cancer. More recently, novel molecular techniques and molecular markers were developed in our laboratory ad have been applied to increase the detection of micrometastases. We have successfully demonstrated the SLN technique in a pilot study with 80 CRC patients. Additionally, we have identified molecular markers in colon cancer cell lines, tumor tissue and lymph nodes from patients in the pilot study. A larger scale study will provide the statistical significance needed to ultrastage patients with colon cancer and determine which patients may be at risk for recurrence. The specific aims of this proposal are: 1) to determine the accuracy and sensitivity of intraoperative lymph node mapping and SLN biopsy in patients with CRC; 2) to evaluate molecular and immunohistochemical methods of detection of micrometastases in the SLN; and, 3) to evaluate the clinicopathological utility of ultrastaging in predicting disease recurrence. This proposed approach may ultimately improve the selection of patients for adjuvant therapy following resection of early-stage colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LYSYL OXIDASE GENE MUTATIONS IN COLON CANCER Principal Investigator & Institution: Csiszar, Katalin; None; University of Hawaii at Manoa 2500 Campus Rd Honolulu, HI 96822 Timing: Fiscal Year 2001; Project Start 01-MAY-1997; Project End 30-APR-2003 Summary: The overall goal of this proposal is to define the role of new putative tumor suppressor gene located at the q23 locus on human chromosome 5 in the development of colon cancer. Lysyl oxidase is a multifunctional, copper-dependent amine oxidase responsible for the development of lysine-derived crosslinks in the extracellular matrix proteins, collagen and elastin. Over the last five years, several groups of investigators, including ourselves, have shown that this enzyme also exhibits a ras-related growth regulatory function. We have recently completed the detailed characterization of the entire human lysyl oxidase gene, including the localization of this gene to the q23 region of chromosome 5 and the identification of two informative polymorphic markers within exon 1 and 10kb upstream of the lysyl oxidase gene. These polymorphisms were used to establish loss of heterozygosity within the 5q23 locus in tumor DNA from approximately 20% of a cohort of 98 patients diagnosed with colorectal cancer. Moreover, in three of these patients, a lysyl oxidase gene mutation was identified in the surviving allele in these tumor DNA samples. This data supports our hypothesis that deletions and mutations at 5q23, involving a new putative tumor suppressor encoded by the lysyl oxidase gene, are involved in the development of colon cancer. This proposal seeks to characterize these 5q23 rearrange- ments in order to begin to understand the role of lysyl oxidase gene mutations in the cascade of genetic events that lead to colorectal tumorigenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MEASUREMENT SEMIPARAMETRICS
ERROR,
MISSING
DATA
AND
Principal Investigator & Institution: Wang, Naisyin J.; Associate Professor of Statistics & Toxi; Statistics; Texas A&M University System College Station, TX 778433578 Timing: Fiscal Year 2002; Project Start 21-APR-1997; Project End 31-MAR-2006 Summary: (provided by applicant): This proposal reflects our continuing interest in solving problems of measurement error, missing data in general regression settings. The proposed research topics naturally arise from two important studies: (i) Colon Cancer Tumorigenesis Project, which consists of a series of experiments to study colon cancer tumorigenesis at the cellular level, and (ii) Prostate Cancer Outcomes Study, which is the largest multicenter observational study to investigate the link between medical practices in the uncontrolled real-world environment and health-related quality of life (HRQOL) among men diagnosed with prostate cancer. We propose to study five primary research topics: Developing efficient generalized estimating equation (GEE) procedure under non- and semi-parametric marginal regression models. Estimating a dynamic correlation between two variables, such as apoptosis (cell death) and DNA adduct damage, as a function of a continuous covariate, cell positions within a colon crypt. Developing methodologies to accommodate a new type of covariate measurement error problem caused by using predictions from a secondary mixed model as the covariate in the primary model. Accommodating analyses of incomplete data through utilizing various multiple imputation procedures including non- and semi-parametric imputations. Adopting approximate saddle point methods to statistical inferences that are suitable to analyze data from a small number of subjects/clusters/units. The major focus of the proposal is development of efficient, easily calculable methods without
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imposing unnecessary parametric assumptions. Special emphasis will be given to correlated observations collected from longitudinal and clustered studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: MECHANISMS OF ADENOVIRUS VACCINES FOR COLON CANCER Principal Investigator & Institution: Eck, Stephen L.; Director, Clinical Oncology; Wistar Institute Philadelphia, PA 191044268 Timing: Fiscal Year 2001 Summary: The major goal of this project is to identify an optimal adenovirus- based vaccination strategy against homologue (mEGP) of the human colorectal carcinomaassociated GA733 antigen. Since mice express mEGP on normal tissues (similar to GA733 Ag in humans), this animal model allows testing of the vaccine in an immunologically tolerant host and evaluation of potential toxicity. These studies will optimize the ability of this vaccine to overcome tolerance to this tumor antigen in settings that closely mimic patients with colon cancer. Therefore, they will have an impact on the initial human clinical trial (see Project 3, Aim 2) and will provide the basis for the testing of improved human colon cancer vaccines in the near future. We have prepared an adenovirus-based mEGP vaccine and have already shown that it can induce tumor protection in the mouse when used in combination with interleukin-2 (IL2). This is the basis for our proposed series of experiments. Our initial experiments will address issues of immediate clinical relevance, i.e., administration of the vaccine by a cutaneous route, the need for one versus two doses of the vaccine, and the appropriate use of cytokine. Having identified parameters that limit or enhance our vaccine in a subcutaneous tumor model, we will than address whether our vaccination strategy is effective against more advanced and metastatic disease. This will provide us with the opportunity to improve our vaccine by studying the effects of different booster strategies, the use of other cytokines and the use of functionally active fragments (from Project 1) of mEGP. Having optimized our vaccine, we will study its mechanism of action by defining the target cells through which the adenovirus elicits anti-mEGP immunity, the role of the adenoviral proteins in the induction of the immune response, and the cell types that contribute to the effectiveness of the immune response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: METABOLISM AND CARCINOGENICITY OF HETEROCYCLIC AMINES Principal Investigator & Institution: Zenser, Terry V.; Internal Medicine; St. Louis University St. Louis, MO 63110 Timing: Fiscal Year 2003; Project Start 01-JUL-1998; Project End 31-AUG-2008 Summary: (provided by applicant): Colorectal cancer is one of the leading causes of cancer deaths in the United States. Both cooked red meat intake and chronic inflammation/infection play a role in the etiology of colon cancer. During the cooking process, genotoxic heterocyclic amines (HCAs), i.e., 2-amino-3-methylimidazo[4,5f]quinoline (IQ), are formed which can initiate colon cancer. Colorectal carcinoma incidence in patients with inflammatory bowel disease is 20-fold higher and occurs 20 years earlier than the general population. Findings in patients are paralleled in animal models with persistent severe inflammation in the colonic mucosa thought to cause development of colorectal cancer. Dextran sulfate sodium (DSS)-induced colitis is an animal model for studying both inflammation and colitis-associated neoplasia. Reactive
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nitrogen oxygen species (RNOS), components of the inflammatory response, contribute to deleterious effects of inflammation. RNOS catalyze nitrosation, oxidation, and nitration reactions. However, the influence of RNOS on HCA carcinogenicity has not been evaluated. Such an evaluation is essential to understanding the strong association between cooked red meat intake and chronic infection/inflammation in colon cancer. Because we recently demonstrated RNOS transformation of IQ to an N-nitroso product N-NO-IQ), which forms DNA adducts and is mutagenic, we hypothesize that RNOS derived from the inflammatory response react with HCAs forming N-nitroso products that initiate colon cancer. Critical to testing this hypothesis is the identification and measurement of N-nitroso products in animals and cells responding to inflammatory stimuli; the demonstration that N-nitroso products are genotoxic and that HCA-induced colon cancer is increased in DSS-treated mice. The following specific aims will test our hypothesis: 1. Investigate HCA transformation by RNOS; 2. Determine reactivity and potential genotoxicity of HCAs and their RNOS-derived N-nitroso products; 3. Evaluate formation and metabolism of N-NO-IQ and its products by in vitro cellular systems, using inflammatory models; 4. Assess formation and metabolism of N-NO-IQ in mice with DSS-induced colitis; 5. Determine effect of DSS-induced colitis inflammation) in IQ carcinogenicity. The long-term goal is to understand the role of RNOS on HCA carcinogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: METHYLATION PROFILING IN COLORECTAL CANCER Principal Investigator & Institution: Issa, Jean-Pierre J.; Professor of Medicine; Leukemia Developmental Res; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 12-MAR-2001; Project End 29-FEB-2004 Summary: The molecular phenotyping of human tumors has yielded potentially important therapeutic prognostic information. In colon cancer, for example, chromosome 18 deletion identifies a subgroup of patients at high risk for relapse following surgical resection, and who may benefit from adjuvant chemotherapy. By contrast, the microsatellite instability (MSI) phenotype identifies patients who may be at lower risk of progression and may have higher cure rate compared to similar stage cancers. In the past few years, CpG island hypermethylation and silencing of genes has emerged as one of the most common molecular changes in neoplasia. Recent work has put in evidence a novel pathway in colorectal tumorigenesis termed CpG Island Methylator Phenotype (CIMP), which effects about 50 percent of the cases. CIMP appears to lead to tumor formation/progression through the simultaneous methylation of multiple genes. In colon cancer, CIMP is associated with a distinct genetic profile, with a high (30 percent) rate of MSI, a high (90 percent) rate of K-RAS mutations in MSInegative cases, and a low (25 percent) rate of p53 mutations. These data suggest that CIMP may add an important layer of information in the molecular phenotyping of malignances for prognostic purposes. In this grant, we propose to explore this issue in colon cancer using large series of uniformly treated patients entered on ECOG protocols. By determining the methylation and mutation/deletion profiles of 780 cases, we determine specifically (1) the prognostic/predictive significance of CIMP and genespecific methylation for relapse rates in limited stage disease (following primary treatment), response rate to chemotherapy in advanced stage disease an overall survival in both groups and (2) the interactions between genetic and epigenetic events in neoplasia and the prognostic/predictive significance of combined epigenetic and genetic profiling. Ultimately, this work aims at establishing that methylation profiling
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may carry the same clinical implications as that already established for genetic profiling in neoplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: MIRK KINASE IN COLON CANCER DEVELOPMENT Principal Investigator & Institution: Friedman, Eileen A.; Jones/Rohner Professor of Pathology; Pathology; Upstate Medical University Research Administration Syracuse, NY 13210 Timing: Fiscal Year 2001; Project Start 01-JUN-1995; Project End 31-MAR-2006 Summary: (Adapted from the investigator's abstract) Mirk is a constitutively active protein kinase which can mediate cell survival in the absence of mitogens. Transiently transfected mirk activates the erk subfamily of MAP kinases in the absence of growth factors or serum. Stable mirk transfectants, under serum-free conditions in which they grow and survive, and vector control cells do not, exhibit a low constitutive activation of erks, 5-fold over that of vector control cells, and more response to mitogens. These observations are likely to be physiologically relevant, not simply an artifact of overexpression or an adaptation of transfectants to culture, because mirk is required for one of the known survival factors, insulin-like growth factor 1 (IGF-1) to function as a mitogen. When mirk protein levels in NIH3T3 cells were decreased by phosphorothiolated antisense oligonucleotides, IGF-1 no longer was a mitogen for these cells. Varying the dosage of the antisense oligos caused a dose-dependent decrease in IGF-1 response, so the more mirk was reduced, the less mitogenic IGF-1 was. Therefore, endogenous levels of mirk are necessary for mitogenic response in vivo. There is also reciprocal regulation between erks and mirk: overexpressed mirk activates erks, whereas sustained activation of erks downregulate mirk. Mirk is relevant to cancer. Stable overexpression of mirk occurs in vivo in a large subset of colon cancers which exhibit mirk levels 5-40-fold those in paired normal colon. If wild-type mirk is stably overexpressed in 2 colon cancer cell lines, cells grow and survive in serum-free conditions in a mirk-dependent manner, with no effect of kinase-inactive mirk. Aim 1 :analysis of the role of mirk in erk activation. The regions of mirk necessary to activate erks in transient transfection experiments will be determined by mutation/deletion analysis. Mirk may activate erks by phosphorylating some component of the erk signaling cascade. This in vivo substrate will be found by using mirk as "bait" in a yeast two-hybrid complementation assay to screen a human skeletal muscle cDNA library. Mirk may modulate erk signaling so the capacity of mirk to activate promoter elements linked to reporter genes will be assayed by transient co-transfections. Aim 2 : analysis of mirk regulation by erks. Whether erk regulation is transcriptional or post-transcriptional will be determined using conditions in which (a) erk activation is blocked and mirk protein levels rise several fold, (b) erks undergo a sustained activation and mirk levels decrease several fold. Mirk is a MAP kinase substrate with erk phosphorylation sites in its C'terminus. The role of erks, if any, in generation of a C'terminal deleted 57 kDa nuclear mirk species will be determined, as will the biological properties of this C'terminal deleted mirk. Aim 3 : measurement of mirk protein expression by immunohistochemistry in human cancer tissues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MODELS FOR THE MOLECULAR CLASSIFICATION OF TUMORS Principal Investigator & Institution: Rao, Jonnagadda S.; Associate Professor; Epidemiology and Biostatistics; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106
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Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2006 Summary: (provided by Applicant) This proposal will develop a series of statistical predictive models to test the hypothesis that differences in patterns of gene expression determine the differing biologic behaviors between colon cancers that are curable with primary surgical therapy, and those that ultimately metastasize to the liver and kill. To generate data to test this hypothesis, Dr. Sanford Markowitz and his colleagues in the cancer genetics program at the Case Western Reserve University-NCI designated Comprehensive Cancer Center have established a series of data archives. The primary archive contains metastatic and non-metastatic colon cancers, anatomical staging information, clinical follow-up information and gene expressions collected on Affymetrix human 40K GeneChips using Eos Biotechnology Inc. expression algorithms. Further, an independent validation archive of 350 colon cancers containing anatomical staging information and clinical follow-up data. In addition promising candidate genes can be assayed for expression from colon cancers in this archive. The goal is to develop predictive models that will identify genes making up a so-called "metastatic signature" for colon cancer. In order to accomplish this, Dr. J. Sunil Rao of the Department of Epidemiology and Biostatistics at CWRU has established a mentoring relationship with Dr. Markowitz in which Dr. Rao will use some recent predictive data mining tools with modifications necessary for modeling of this data. Specifically, Dr. Rao will develop methods that: 1) incorporate measurement error and differential variability for gene expressions; 2) aggregate tree-based classifiers from resampled data (bagging) for accurate predictions; 3) refine bagging using a within-cluster type of bagging for further increased prediction accuracy; 4) cluster observations (and genes) based on estimating a finite mixture of Gamma distributions using approximate Bayesian computing and Dirichlet process priors; 5) formally deal with tuning parameters implicit in the treebuilding process; and lastly, 6) collate results into a high-dimensional visual graphic known as the CAT scan for extracting the nature of the hypothesized metastatic signature. A full theoretical and empirical evaluation of all algorithms using simulations and the two colon cancer archives will be made. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: MOLECULAR ANALYSES OF MLH3 NULL MICE Principal Investigator & Institution: Lipkin, Steven M.; Medicine; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2001; Project Start 20-SEP-2001; Project End 31-AUG-2004 Summary: (Applicant's Description) My goal is to establish a research program as an independent investigator. My long-term objective is to study basic and clinical aspects of Genetic Cancer Susceptibility, with a focus on mammalian genetics and genomics. The purpose of the proposed study is to test the hypothesis that targeted mutation of a novel mammalian DNA mismatch repair gene cloned in our laboratory, MLH3, causes genetic susceptibility to cancer, with particular reference to gastrointestinal and lymphoid cancer. Six mammalian homologues of yeast DNA mismatch repair genes associated with microsatellite instability have previously been described: MLH1, MSH2, MSH3, MSH6, PMS1, and PMS2. Each one of these genes is associated with genetic susceptibility to cancer in humans (specifically, Hereditary Non-Polyposis Colon Cancer) and/or mice. As yeast mlh3 is similarly associated with MSI, this proposal examines the role of MLH3 in mammalian DNA mismatch repair and tests whether Mlh3 knockout mice are genetically susceptible to cancer. Specific aims are: (1) To generate antibodies against Mlh3 for immunohistochemical analyses. (2) To generate mice that are deficient in Mlh3 and mice that are compound deficient in Mlh3 and the
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Pms2 DNA mismatch repair genes. Experiments in yeast suggest that mlh3 and pms2 are both involved in the repair of insertion/deletion loops of mismatched genomic DNA. Mlh3/Pms2 compound mutant mice would therefore be predicted to have a more severe phenotype than mice mutant for either protein separately. These mouse lines will be analyzed for susceptibility to cancer, with special emphasis on gastrointestinal and lymphoid systems. (3) To test the hypothesis that mutations in mammalian Mlh3 cause defects in DNA mismatch repair. We will utilize both Mlh3 and Mlh3/Pms2 null mice as a source of colonic epithelial cells to analyze microsatellite instability. These data will help to prioritize families with a hereditary predisposition to colon cancer for future MLH3 candidate gene mutation analyses. (4) To examine the effect of Mlh3 deficiency on the Apc tumor suppressor gene. Colon cancer cell lines with mutations in the MLH1 gene accumulate mutations in the tumor suppressor gene APC. We will generate mouse lines that are mutant for mlh3 and heterozygous for a mutant Apc A1638N allele that predisposes to spontaneous colorectal cancers. The analysis of the tumor spectrum and the onset and progression of tumor formation will indicate the role of Mlh3 in gastrointestinal cancer susceptibility and provide a detailed analysis of the spectrum of Apc mutations resulting from mlh3 deficiency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: MOLECULAR BIOMARKERS Principal Investigator & Institution: Wogan, Gerald N.; Professor; Division of Toxicology; Massachusetts Institute of Technology Cambridge, MA 02139 Timing: Fiscal Year 2001; Project Start 25-SEP-1990; Project End 31-MAY-2002 Summary: The overall objectives of this program are to refine and validate molecular biomarkers of human exposures to aromatic and heterocyclic amines, and to utilize the markers to determine the roles of heterocyclic amines on the risk of colon cancer and aromatic amines on the risk of bladder cancer in smokers and nonsmokers in different racial and ethnic groups. In Los Angeles, these will include Latinos, African Americans, Japanese and Whites; defined cohorts will also be studied in Singapore, China and Japan. In Project I, hemoglobin adducts will be used to determine the extent of human exposure to N.hydroxyalkylanilines, as well as the key enzymes regulating their activation. Urinary metabolite excretion will be used to determine metabolic polymorphisms and exposure of different racial and ethnic groups to specific heterocyclic amines, and also determine the relationship between exposure and colon cancer in case- control studies. In project 2, methods for measuring heterocyclic amineDNA adducts in urine and cellular DNA will be developed and validated as markers of biologically effective exposures. The markers will be used to determine relationships between DNA adduct formation and risk of colon cancer in case control studies and to assess exposure in different racial and ethnic groups. Methodology for measuring the major DNA adduct of 4- aminobiphenyl in urine and cellular DNA will be developed and used to determine relationships between DNA adduct formation and risk of bladder cancer in a case-control study. In addition, methodology will be developed for measurement of total DNA adduct levels in cellular DNA in order to assess possible interactions among diverse carcinogen exposures. Project 3 will determine prevalence of exposure to heterocyclic amines and alkylanilines among different racial and ethnic groups, and also determine dietary and other possible environmental correlates of exposure to these compounds within and between racial-ethnic groups. Additionally, preliminary studies will be conducted to investigate relationships between exposure to heterocyclic amines and colorectal cancer, and between arylamine and alkylaniline exposure and bladder cancer. Interrelationships between different biomarkers and each
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other and to target tissue levels, as well as relationships to enzymatic genotypes/phenotypes within and between racial/ethnic groups will also be investigated. Together, the individual projects will provide complementary data for assessing the validity of molecular biomarkers in measuring biologically effective exposures, and testing the hypothesis that exposure to aromatic and heterocyclic amines increases risk for bladder and colon and pancreatic cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: MOLECULAR BIOMARKERS OF EXPOSURE AND SUSCEPTIBILITY IN HUMAN COLON CANCER Principal Investigator & Institution: Strickland, Paul T.; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001 Summary: A major route of exposure to environmental carcinogens is through the diet. Epidemiological studies indicate the 20 to 50 percent of all human cancers can be attributed to dietary causes. The frequent consumption of animal fat, red meats, or grilled/smoked meats has been associated with increased risk for cancers of the gastrointestinal tract and pancreas. In contrast to the strong association between aflatoxin and liver cancer described in other projects in this program, the specific etiologic agents responsible for causing many diet- associated human cancers have yet to be determined. Two classes of chemical carcinogens, polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (Has), have been indentified in grilled or fried meats. These chemicals produce a variety of cancers, including colon, stomach, breast, and liver cancers, in experimental animal models. The overall goals of this project are to investigate the role of these dietary carcinogens in colon carcinogenesis in humans, and to identify susceptibility factors (effect modifiers) that modulate the metabolism of these carcinogens and, ultimately, colon polyp/cancer risk. Our work hypothesis is that ingestion of dietary carcinogens formed in meat during cooking is a causative factor in the formation of colon polys, preneoplastic lesions that occur early in the process of human colon cancer development. This project (Aim 1 and 2) will examine inter- individual differences in urinary HA and PAH metabolite profiles in subjects ingesting fried or broiled meat during controlled feeding studies. Relevant metabolic phenotypes and potential confounders will be assessed to investigate their role in intra-and inter-individual differences. These studies should provide insight into the biological basis for inter-individual variation in response to ingestion of carcinogens found in cooked meats. This project ( Aim 3 and 4) will also evaluate the association of these biomarkers of exposure and metabolism with risk of colon polyp development in a case-control and a case-case study. The identification of critical metabolic and dietary determinants of colon polyp risk should lead to new approaches for prevention of colon polyps and cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR BIOMARKERS/NON-INVASIVE DIAGNOSIS OF COLON CA Principal Investigator & Institution: Gupta, Smiti V.; Oxford Biomedical Research, Inc. Box 522, 4600 Gardner Rd Metamora, MI 48455 Timing: Fiscal Year 2002; Project Start 22-JUL-2002; Project End 31-DEC-2003 Summary: (provided by applicant): Colorectal cancer is a leading cause of death in the United States. There is very strong evidence that screening for this disease can reduce
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colorectal cancer mortality. Present screening methods include fecal occult blood testing (FOBT) and endoscopy, which can detect some early colon cancers and large polyps. However, FOBT screening suffers from large numbers of false positive and negative results. Whereas periodic sigmoidoscopy can significantly reduce mortality from colon cancer, currently only about 7 percent of eligible persons receive sigmoidoscopic screening. The goal of this project is to develop novel non-invasive molecular biomarkers for the diagnosis of human colon cancer based on multiplex PCR amplification of mRNA coding for eicosanoid-metabolizing enzymes in fecal matter, using quantitative PCR methodology. The expression of the target genes will be normalized relative to an epithelial and a leukocyte cell marker, cytokeratine-19 and leukocyte , respectively. In preliminary studies, significant levels of Cox-2 mRNA were found in fecal matter of older Min mice, with little or no Cox-2 mRNA in the fecal matter of young Min mice or control wild type mice. Specific aims for Phase I research include: development and optimization of real-time multiplex RT-PCR conditions suitable for isolation and quantification of selected mRNA species in human fecal matter, and preliminary studies on the utility of quantitative multiplex RT-PCR for the diagnosis of human colon cancer using coded fecal samples obtained from normal individuals and from colon cancer patients prior to surgical removal of the colon. PROPOSED COMMERCIAL APPLICATIONS: There is a great need, and a very larger market for a reliable non-invasive diagnostic screening test for human colon cancer. The multiplex RT-PCR quantification of fecal mRNAs which encode selected proteins in eicosanoid metabolism and inflammatory pathways is expected to provide a sensitive and reliable method for the differential diagnosis of human colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: MOLECULAR CLASSIFICATION OF COLON TUMORS Principal Investigator & Institution: Augenlicht, Leonard H.; Professor & Director, Molecular Oncology; Montefiore Medical Center (Bronx, Ny) Bronx, NY 104672490 Timing: Fiscal Year 2001; Project Start 28-AUG-2000; Project End 31-JAN-2005 Summary: The Albert Einstein Cancer Center has been in the forefront of development of technologies for the analysis of gene expression, beginning with the first large scale gene array and image analysis systems developed over a decade ago, and continuing to high throughput genomics facilities for microarray analysis, mapping and sequencing, and novel technologies for quantitative in situ analysis of multiple mRNA molecules at single molecule resolution and sensitivity. An integrated program utilizing these technologies is presented that focuses on identifying subsets of Dukes' B2 and C colon cancer patients, an area of basic and clinical research in which we have been active throughout this decade. Approximately 50,000 patients per year will have adjuvant chemotherapy recommended following resection, and there is a critical need to distinguish subsets who will benefit from this treatment from subsets who either do not require further treatment, or who will not benefit, and should be spared the expense and toxicity of treatment, The latter patients with poor prognosis would also be candidates for more aggressive treatment, including gene therapy. Patients will be identified and tissue obtained through a collaborative program among the Departments of Surgery, Pathology and Oncology for capturing and following patients on clinical trials. A unique feature of our application is our development and analysis of extensive microarray databases on lineage specific differentiation of colonic epithelial cells both accompanied by, or independent of, apoptotic pathways, and our microarray analysis of isogenic colonic cell lines that over-express c-myc mRNA and protein to differing degrees. These in vitro data provide biological rationales which will help guide analyses
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of the in vivo data. In addition to fully operational facilities, other unique features of our program include the use of Real Time PCR for microarray calibration and quality control, and analysis of tissue obtained by laser capture microscopy; linkage to major programs in structural genomics and development and analysis of novel mouse models of colon cancer; an in place bioinformatics program which services the genomics and genetics programs of the Cancer Center; the collaboration of a biostatistics group with extensive experience in basic and translational research for the planning and analysis of the experiments; and a resource of banked normal and tumor DNA from over 700 patients entered into 2 phase III studies of adjuvant therapy for colon cancer, including the last multi- institutional study for which there is a control arm for analysis of the natural history of the disease, which will permit rigorous analysis of structural gene alterations that may underlie alterations in expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: MOLECULAR GENETICS OF COLON CANCER IN BLACKS AND WHITES Principal Investigator & Institution: Hu, Jennifer J.; Assistant Professor; Cancer Biology; Wake Forest University Health Sciences Winston-Salem, NC 27157 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 28-FEB-2006 Summary: (provided by applicant): Colon cancer is the second leading cause of cancer deaths in the U.S. Despite rapid advances in human genetics, critical questions about genetic susceptibility to, and prevention of, colon cancer remain unanswered, particularly for African-Americans, who have a higher incidence and mortality rate. Our primary objective is to evaluate genetic susceptibility and environmental factors that might explain the diverging incidence and mortality trends in blacks and whites. Our secondary objective is to assess the mechanisms involved in gene-gene and geneenvironment interactions and to identify high-risk (sub)populations and modifiable risk factors for colon cancer. Then it may be possible to closely tailor etiology-driven preventive strategies to the specific genetic defects conferring individual risk. We will evaluate the association between colon cancer risk and two phase II metabolic detoxification genes (GSTM]/T1), two base excision repair genes (XRCC1 and APE), a gene in double-strand break/recombination repair (XRCC3), and a nucleotide excision repair gene (XPD). The proposed study will use the existing genomic DNA samples and exposure data collected in the NCI-funded North Carolina Colon Cancer Study (NCCCS) (CA 66635). The NCCCS is a well-designed, large population-based, casecontrol study in a 33-county area of North Carolina with 800 newly diagnosed colon cancer cases and 800 age- and race-matched controls (50 percent blacks and 50 percent whites). The parent study is on target to complete sample and data collection by our proposed start date of January 1, 2002. The high percentage of black participants (50 percent) provides the unique opportunity to study specific risk factors in AfricanAmericans, an understudied population at increased risk of fatal colon cancer. The large sample size provides substantial statistical power for the assessment of gene-gene and gene-exposure interactions in colon cancer risk. Our preliminary pilot data demonstrated black-white differences in genotype distributions and environmental exposures. We also observed gene-gene and gene-environment interactions in colon cancer risk. This proposed research will fill the gap between colon cancer risk assessment and prevention. Confirmation of risk profile(s) will be useful in identifying persons at high risk of colon cancer for screening and intervention. Characterization of gene-environment interactions will provideeffective strategies for dietary and lifestyle interventions, particularly in genetically susceptible (sub)populations.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: MOLECULAR MARKERS OF PROGNOSIS IN COLON CANCER Principal Investigator & Institution: Warren, Robert S.; Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 03-MAR-2000; Project End 28-FEB-2005 Summary: (adapted from the investigator's abstract) Colon cancer is a heterogeneous disease whose clinical behavior is incompletely predicted by the present staging system. A precise understanding of the biology of individual tumors is required for both appropriate clinical decision-making and development of new cancer therapies. The goal of our work is to characterize an individual patient's tumor in sufficient detail to allow selection of optimal therapy. By studying tumor markers that illustrate differences in the function of the tumor cells compared to normal tissue, we will also identify biologic processes that are potential targets for new cancer treatments. Achieving this goal involves two main activities. First, subgroups of patients within the present staging system that respond either well or poorly to current adjuvant therapies must be identified. There are a large number of tumor-specific prognostic factors available to meet this goal, but because these have never been studied in combination in large prospective clinical trials, their utility is not proven. Second, we must further our study of colon cancer biology through preserving a resource that will allow evaluation of new markers as they are developed. Unless many different markers are studied in relation to each other, the importance of genes associated with genomic instability, cell cycle progression, tumor metastasis and resistance to therapy in patients participating in Intergroup adjuvant therapy trials for either Stage II or Stage III colon cancer (CALGB 9581 and 89803, respectively) and to correlate these values with time to recurrence and overall survival. We will also develop and validate a new method of measuring gene expression in fixed, embedded tissue which will markedly expand the ability to correlate marker expression and outcome in cooperative group cancer trial patients. The results of these studies will have great clinical importance as it will allow clinicians to avoid toxic and costly treatment of patients unlikely to benefit from this and will help to tailor adjuvant therapy to individual patients based upon a molecular marker profile and potentially, and may reveal targets for the development of new therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MUC1 - SPECIFIC IMMUNOTHERAPY OF COLON CANCER Principal Investigator & Institution: Akporiaye, Emmanuel T.; Professor; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Colorectal cancer is the second leading cause of cancer death in the United States. Conventional therapies including surgery, radiation and chemotherapy have shown limited success with an average 5-year survival of only 8 percent in patients with metastatic disease. Thus recent efforts have focused on cyclooxygenase-2 (COX-2) inhibitors to decrease the risk of colon cancer. These agents reduce the size and frequency of intestinal polyps in adenomatous polyposis coli (APC)deficient mice and in humans harboring the familial adenomatous polyposis (FAP) mutation. However, cessation of drug therapy results in re-emergence of disease and subsequent mortality. With the goal of achieving durable responses, we propose a therapeutic approach that is antigen-specific and induces long-term tumor immunity. We have chosen to focus on MUC1, an epithelial mucin that is aberrantly expressed in
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colon cancer. MUC1 is recognized by cytotoxic T lymphocytes and therefore represents a unique target for antigen-specific immunotherapy. The goal of this project is to develop dendritic cell-based vaccines to treat MUCl-expressing adenomas and colon carcinoma in animal models and in colon cancer patients. The hypothesis to be tested is that spontaneously arising MUCl-expressing adenomas or colon carcinoma can be successfully treated using dendritic cell-based vaccines. The Specific Aims of this study are to: 1) develop human MUCl-expressing transgenic mice that spontaneously develop intestinal adenomas and carcinomas 2) develop effective MUCl-specific DC-based vaccines capable of preventing or abrogating adenomatous polyps and carcinoma, 3) conduct pre-clinical in vitro studies using DC-based vaccines to stimulate T cells isolated from colon cancer patients, 4) evaluate the ability of MUCl-specific, DC-based vaccines to induce immunologic responses in colon and pancreatic cancer patients. The MUCl-expressing mice will be generated by crossing the APC-min mouse (Min) or the PI3K-gamma null mouse (PI3K-gamma -/-) with a transgenic mouse expressing human MUC1 (MUC1.Tg). The Min mouse is a strain containing a fully penetrant mutation in the APC tumor suppressor gene leading to the spontaneous development of gastrointestinal adenomas by 3-4 months of age. PI3K-gamma null mice result from targeted disruption of the p1107 catalytic subunit of phosphoinositide-3OH kinase(PI3K-gamma). As with human colorectal cancer, these mice develop spontaneous multifocal adenomas which progress to invasive colorectal adenocarcinomas. The proposed studies are expected to result in the development of novel DC-based vaccines for the prevention and/or treatment of colorectal cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: MUCIN GLYCOPROTEINS IN COLON CANCER METASTASIS Principal Investigator & Institution: Bresalier, Robert S.; Director of Gastrointestinal Oncology; Medicine; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, MI 48202 Timing: Fiscal Year 2001; Project Start 21-JUN-1999; Project End 31-MAR-2003 Summary: Colorectal cancer is the second most common epithelial cancer in North America with an estimated annual mortality of 55,000 in the United States. The majority of colon cancer-related deaths are due to metastasis, a complex multi-step process by which tumor cells escape the primary tumor and establish secondary foci at distant sites. Mucins, the major secreted glycoproteins of the colon and galectin-3 an endogenous mucin binding protein play an important role in colon cancer metastasis. Direct evidence in support of a particular function(s) for mucin and galectin-3 are now emerging through identification of interacting ligands and structural motifs. Mucins are encoded by at least 9 genes and while a role for the MUC2 gene in mucinous carcinomas has been established, it remains to be determined which structural domains of MUC2 and other mucins are necessary to promote metastasis of colon cancer cells. Galectin-3 also consists of distinct structural domains. The protein may be localized in the nucleus, cytoplasm, on the cell surface or be secreted by colon cancer cells, and may therefore act in several ways to promote metastasis. The long-term objective of this proposal is to determine how the cell surface and secreted glycoproteins of colon cancer cells influence their metastatic capacity. Based on progress during the current funding period efforts will continue which are designed to elucidate the structure-function relationships between colon cancer mucins, mucin-binding proteins and metastasis. We hypothesize that specific structural domains of mucin apoproteins and glaectin-3 are necessary for their metastasis-enhancing effects, and that these molecules interact to promote tumor spread during defined stages of colon cancer metastasis. To accomplish these goals the
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following specific aims are proposed 1) Determine which structural domains of mucins are necessary for promoting the metastasis of colon cancer cells 2) Determine whether MUC2 and galectin-3 interact to affect the metastatic potential of colon cancer cells 3) Determine at which stages of liver colonization MUC2 and galectin-3 act to augment the metastatic potential of mucinous colon cancer cells. Further understanding of the roles of mucins and galectin-3 in colon cancer metastasis may make it possible to design specific diagnostic and therapeutic strategies to alter the course of metastatic disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: NATIONAL SURGICAL ADJUVANT BREAST AND BOWEL PROJECT Principal Investigator & Institution: Wolmark, Norman; Associate Professor of Surgery; Nsabp Foundation, Inc. East Commons Professional Bldg Pittsburgh, PA 15212 Timing: Fiscal Year 2003; Project Start 01-DEC-1976; Project End 31-JAN-2006 Summary: (provided by applicant) 4 COLLABORATING INSTITUTION (S) 4 HUMAN SUBJECTS RESUME 4 OVERALL RECOMMENDATION 5 COLORECTAL COMMITTEE 5 THE BEHAVIORAL AND HEALTH OUTCOMES (BAHO) COMMITTEE 12 COMMITTEE BUDGET RECOMMENDATIONS 15 SRG SUBCOMMITTEE H ROSTER OVERALL (provided by applicant): In the spring of 2000, the National Surgical Adjuvant Breast and Bowel Project (NSABP) was notified that its colorectal and quality-of-life components had received a peer review rating of less than excellent and, as such, would receive three years of support from the National Cancer Institute, rather than the requested six years. During the past 22 months, the NSABP has: * maintained program strengths such as outstanding protocol accrual, data quality, and integrity; * restructured its Quality-of-Life Committee to better address the weaknesses identified during peer review; and * reviewed the scientific research agendas of both committees and revamped the NSABP's infrastructure to better support the work of those committees. The specific aims of this current proposal are: * to affirm that the NSABP has made substantial progress in addressing the programmatic weaknesses identified during the previous competitive renewal process; * to provide an interim progress report, plans, and future directions of these committees; and * to gain continued funding and NCI support to proceed with the colorectal and quality of life scientific agendas of the NSABP. Continued support of these relevant, important areas is essential for the well-being of cancer patients and is critical to the success of both the NSABP's and the NCI's missions. COLLABORATING INSTITUTION(S): University of California, Los Angeles, CA Christiana Care Health Services, Newark, DE THE FOLLOWING RESUME SECTIONS WERE PREPARED BY THE SCIENTIFIC REVIEW ADMINISTRATOR TO SUMMARIZE THE OUTCOME OF DISCUSSIONS OF THE REVIEW COMMITTEE ON THE FOLLOWING ISSUES: HUMAN SUBJECTS RESUME The Chair of the NSABP is ultimately responsible for establishing and supervising systems and procedures by which the NSABP Foundation, as grantee, and the granting agencies are assured that NSABP and its member institutions are in full compliance with applicable federal regulations, including those relating to conduct of research involving human subjects and tissues. All human subjects protections are in place and there are no concerns. Each individual NSABP protocol includes plans for the inclusion of women and minorities along with plans for sex/gender and racial/ethnic subgroup analysis. The Patient Advocacy Committee along with the Diversity Strategic Planning Committee have developed programs to increase awareness of clinical trials in diverse patient populations. Additionally the NSABP is beginning a partnership with the National Black Leadership Initiative on Cancer to increase minority recruitment in
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clinical trials PROTECTION OF HUMAN SUBJECTS (Resume): The protection of patients from research risks is critical to the NSABP. The NSABP ensures that adequate safeguards are in place to reduce any risks and to eliminate them when possible including risk to confidentially of patient information. There are no human subject concerns. INCLUSION OF WOMEN PLAN (Resume): There is no systematic exclusion of patients based on gender. Females are appropriately represented in NSABP clinical trials. The proportion of women enrolled on ongoing colon cancer trials compare to the age-adjusted SEER incidence rates. Acceptable, G1A. INCLUSION OF MINORITIES PLAN (Resume): There is no systematic exclusion of patients based on race and or ethnicity. Overall approximately 14 percent of all patients on NSABP trials are from minority populations. Minorities are appropriately represented in NSABP clinical trials. Acceptable, M1A. INCLUSION OF CHILDREN PLAN (Resume): Children are not included in NSABP protocols because the number of children with breast and colorectal cancer is limited and because the majority of children with cancer are accessed by the Children's Oncology Group. Children are exempt based on Exclusion 4b of the "NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects". Acceptable, C1A. OVERALL RECOMMENDATION The NSABP Colorectal Committee and Behavioral and Health Outcomes (BAHO) Committee are both recommended with an Excellent to Outstanding level of merit. Funding is recommended for the requested three years. Budget recommendations are detailed in the body of the text. COLORECTAL COMMITTEE Three years ago the Colorectal program received a very good merit rating with three years of funding. The program is now being reviewed for an additional three year of support in order to bring this committee back into the full cooperative group six year review cycle. One of the great strengths of the NSABP's colorectal cancer effort has been their high level of accrual to clinical trials. During the current funding period, the NSABP was responsible for 44 percent of all accruals to NCI-sponsored colorectal cancer clinical trials. In two years, the NSABP accrued 1,530 subjects to a single adjuvant protocol, C-07. Dr. Nicholas Petrelli continues as chair of the Colorectal Committee. He has established expertise in administration and clinical trials in colorectal cancer. He is fully qualified for this position. Dr. Carmen Allegra replaces Dr. Pazdur as co-chair. This appointment provides needed expertise in laboratory correlative science methodology and insight. The appointment of Dr. Michael O'Connell as Associate Chairman for Treatment adds strength and connection to the GI Intergroup. Dr. Roy Smith is Director of the Division of Medical Oversight. It is stated that he will play an important role in colorectal protocol development, yet his experience in this area is limited. Dr. Paik is leading an aggressive correlative science program. Future directions for this committee involve combining targeted therapies with cytotoxic chemotherapy as a colon adjuvant strategy, systemic and regional chemotherapy after hepatic resection, the polyp prevention protocol, and Phase II trials in patients with advanced disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: NATURALLY OCCURING SHPINGOLIPIDS AND SPINGOLIPID ANALOGS Principal Investigator & Institution: Merrill, Alfred H.; Professor; Biochemistry; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2001 Summary: The ceramide and sphingoid base backbones of sphingolipids are highly bioactive compounds that affect growth, differentiation, cell migration and apoptosis when added to transformed cells in culture. These findings have been shown to be
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relevant to cancer in vivo because addition of sphingolipids to the diets of CT1 mice that have been treated with a colon carcinogen (1,2-dimethylhydrazine) to Min mice (with a genetic defect in APC that predisposes them to cancer) reduces early indices of colon carcinogenesis (colonic cell proliferation and appearance of aberrant colonic crypt foci) as well as decreases the number of tumors. Based on the mechanisms of action of ceramides and sphingo bases (and structure- function relationships for the metabolism of these compounds), synthetic analogs have been prepared that are more potent that the naturally occurring compounds when tested against colon cancer cells in culture. This demonstrates the potential for sphingoid base analogs to be even more effective than ceramide and sphingosine against colon cancer cells. Thus, the goals of this grant are to develop libraries of novel sphingolipid analogs through directed combinatorial syntheses (as well as from selected natural sources), to conduct structure/function studies with these libraries with the goal of elucidating mechanism of action, and to conduct screens of the potency and selectivity of the analogs against in vitro and in vivo cancer models at Emory as well as at the NCI. The findings of these studies will identify the most effective compounds and strategies for use of sphingolipids for the prevention and treatment of colon cancer and, perhaps, other forms of neoplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: NEOPLASTIC COMPLICATIONS IN INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Meltzer, Stephen J.; Professor; Medicine; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2001; Project Start 30-SEP-1993; Project End 31-AUG-2002 Summary: In recent years, our group and others have generated much new knowledge regarding the pathogenesis of ulcerative colitis-associated neoplasias and preneoplasias (UCANs), but much more remains to be discovered. We now know, for example, that tumor suppressor gene is a very early event in UCANs. We have also learned that microsatellite instability (MI) is relatively common and occurs early in UC-associated neoplastic progression, and that in doing so, it targets at least very important growthsuppressive genes, TGF-beta1RII and IGFIIR. The central unifying hypothesis of this proposal is that the p53 inactivation and MI pathways are separate but equally important routes to cancer occurring in ulcerative colitis, and that both are involved very early in this process. We will test this hypothesis by addressing the following Specific Aims: 1. To study MI at anonymous noncoding loci in a large cohort of UCAN patients. 1.a. To determine the occurrence of MI both with neoplastic or preneoplastic lesions and remote from them, as well as in patients without known or previously diagnosed colorectal dysplasia or cancer. 1.b. To apply a novel microassay based on the cloning of single microsatellite alleles, with the aim of detecting MI in histologically normal tissues as well as sera from UC patients. 2. To assess MI at coding region targets in a large cohort of UCAn patients. 2.a. To assess inactivation of IGFIR and TGFbeta1RII by coding region MI, loss of heterozygosity, or diminished IGFIIR or TGFbetaRII expression at the mRNA and protein levels. 2.b. To demonstrate deficient activation of TGF-beta1 by examining expression of the active and latent precursor forms of TGF-beta1, using antibodies specific for each protein, and excessive expression of IGFII ligand, in lesions with or without IGFIR mutations. 2.c. To discover additional, novel coding region targets of MI in UCANs. 3. To develop a dynamic in vitro model of IGFIR function and dysfunction. 3.a. To discover colon cancer cell lines containing IGFIIR inactivating mutations. 3.b. To utilize SW48 colon cells, which possess an IGFIRR mutation, in cell complementation and transfection studies to test the growth
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suppressive activity of IGFIIR. 4. To investigate p53 tumor suppressor gene alterations in a large cohort of UCAN patients. 4.a. To determine whether the p53 inactivation and MI pathways are nonoverlapping. 4.b. To investigate the specific p53 base substitutions in all UC tissues studied, in order to prove the existence of a unique p53 mutational spectrum in UC. 5. To determine the prognostic significance and/or early detection value of p53 inactivation, along with that of MI occurring in noncoding regions and at specific targets, including IGFIR and TGF-beta1RII, using initial and followup clinical correlative parameters in a large cohort of UC patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: NEW METHODS FOR CANCER DETECTION Principal Investigator & Institution: Barany, Francis; Professor; Microbiology and Immunology; Weill Medical College of Cornell Univ New York, NY 10021 Timing: Fiscal Year 2002; Project Start 01-MAR-1997; Project End 30-JUN-2006 Summary: (provided by applicant) This program project application represents an integrated and focused multi-disciplinary approach to molecular profiling of colon cancer for improved individualized treatment of this disease. Over 50,000 patients die each year in the United Sates of uncontrolled metastatic colon cancer. Despite extensive morphological and molecular information, it is presently impossible to predict outcome accurately for individual patients, or to calibrate therapy to the molecular state of the tumor. Thus, there is an urgent need to discover reliable molecular markers or targets for the diagnosis, prognosis, and treatment of cancer. For the better part of a century physicians have relied on histological and clinical criteria for developing prognosis. Unfortunately, while these criteria predict average outcomes, tumor variability prevents meaningful individual prediction and decisions. Preliminary expression profiling of solid tumors using SAGE, cDNA, and oligonucleotide arrays has yielded volumes of data, yet variation between tumors has yielded little concordance among the different techniques, nor accurate predictors of outcome. The current program project application is distinguished from previous approaches by: (i) determining the genetic and epigenetic profiles, (ii) determining mRNA profiles on the same human tumor sample, and (iii) using biostatistic, clustering and neural net analysis to guide gene prioritization and outcome analysis. Our strategic approach is to: (i) Develop and validate colonspecific cDNA arrays, our ligase detection reaction/universal DNA array, and our EndoV/DNA ligase-based technologies for high-throughput detection of cancerassociated expression changes, mutations, deletions, insertions, gene amplification, LOH events, and methylation changes in colon cancers. (ii) Discover and characterize new cancer-pathways genes in invasive adenocarcinomas and metastases based on integrated analysis of expression and mutational profiles. (iii) Identify the patterns of molecular alterations that accumulate in the p53, cell cycle, apoptosis, Wnt signaling, RPTK signaling, and TGF Beta signaling pathway genes in individual tumors. (iv) Describe the progressive and sequential alterations in global gene expression and in the expression of specific cancer pathway genes during the evolution of colon neoplasia from atypical crypt focus to metastasis. (v) Develop a molecular classification of colon carcinogenesis, based upon genetic, epigenetic and mRNA expression profiling, and employ this taxonomy in predicting outcome or response to particular modes of therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NO CHEMOPREVENTION
RELEASING
ASPIRIN
AND
COLON
CANCER
Principal Investigator & Institution: Rigas, Basil A.; Scientist; Institute for Cancer Prevention 1 Dana Rd Valhalla, NY 10595 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (provided by applicant):Chemoprevention has the potential to be a major component of the control of colon cancer, one of the commonest malignancies. Although traditional non-steroidal anti-inflammatory drugs (NSAIDs) prevent colon cancer, their side effects are a major obstacle to their large-scale application to prevent colon cancer. The novel nitric oxide (NO)-releasing NSAIDs (NO-NSAIDs), consisting of a NSAID molecule and a NO-releasing moiety linked to it via a chemical spacer, have been synthesized to overcome NSAID toxicity. Current evidence suggests that they are much safer than traditional NSAIDs. Early studies indicate that an NO-aspirin (NOASA) derivative is much more effective than ASA in cultured cells and against colon preneoplastic lesions. That NO-ASAs have superior effectiveness and safety makes them promising chemopreventive agents and constitutes a compelling argument to study their mechanism of action in colon carcinogenesis. The proposed studies will evaluate two hypotheses: a) NO-ASA compounds share with traditional NSAIDs some of their known mechanisms of action, such as their effects on cell kinetics and on the eicosanoid and NO pathways, all relevant to chemoprevention, and b) Since NO-ASA derivatives are markedly more effective than unmodified ASA, the additions to the ASA molecule to generate NO-ASA impart on it new properties, which make it more effective. Our specific aims are 1) Determine in cultured colon cancer cells the effect of NO-ASA derivatives on cell kinetics (proliferation, apoptosis) and cell cycle; on the eicosanoid pathway (effect on the catalytic activity of COX; COX-1 and -2 expression and regulation; evidence for effects beyond COX); and on the nitric oxide pathway (expression of NOS isoforms; NOS catalytic activity). 2) Determine in an animal model of colon cancer the contribution of the NO-ASA-induced changes to colon carcinogenesis. Based on results from Specific Aim #1, we will select the most promising of the three NO-ASA derivatives and assess its chemopreventive efficacy against azoxymethane-induced colon carcinogenesis in F344 rats. The effect of this compound on cell kinetics and on the two metabolic pathways will be assessed and correlated with chemopreventive efficacy. 3) Assess the contribution of the key structural components of the NO-ASA molecule to their chemopreventive actions. We will study the effects of synthetic molecules representing the structural components of each one of the three NOASA compounds. They include: ASA+spacer (NO- ASA without the -NO2 group) to test the contribution of NO; spacer (the part linking ASA to -NO2) to test its individual contribution; and a NO-donor which releases NO, to further test the role of NO. The long-term goal of these studies is to develop mechanism-driven safe and effective strategies for colon cancer prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: NOVEL BENZAMIDE RIBOSIDE ANALOGUES AS ANTICANCER AGENTS Principal Investigator & Institution: Pankiewicz, Krzysztof W.; Pharmasset, Inc. 1860 Montreal Rd Tucker, GA 30084 Timing: Fiscal Year 2001; Project Start 10-MAY-2001; Project End 30-APR-2004 Summary: (provided by applicant): Colon cancer is a common malignancy (140,000 cases in the USA) and about 50 percent of cases present metastatic disease within 5 years
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of diagnosis. Therefore, there is a need for improved therapies. The overall aim of this proposal is to develop a new agent for the treatment of human colon carcinoma. Previous studies with tiazofurin have shown that it is metabolized to an analogue of NAD, TAD (thiazole-4-carboxamide adenine dinucleotide) that is a potent inhibitor of IMPDH (inosine 5'-monophosphate dehydrogenase). Such inhibition causes selective reduction in guanylates, resulting in not only inhibition of RNA/DNA synthesis but also exhibiting significant antitumor activity. Benzamide riboside (BR), has recently been shown to be metabolized to an NAD analogue, BAD (benzamide adenine dinucleotide), a potent inhibitor of IMPDH that is more cytotoxic to human colon carcinoma HT-29 than tiazofurin. BR demonstrates in vivo antitumor activity. Moreover, unlike tiazofurin, BR induces apoptosis in human ovarian carcinoma N.1 cells. Our recent studies found that stable bis(phosphonate) analogues of TAD and BAD showed even better therapeutic potential than active metabolites TAD and BAD or parent nucleosides. On the basis of a recently solved crystal structure of an IMPDH Type II complex with our NAD analogue (SAD) we propose to synthesize bis(phosphonate) analogues of BAD which will be specific against IMPDH Type II. IMPDH Type I is ubiquitously expressed whereas, IMPDH Type II is expressed in cancer cells including colon carcinoma. In additon, we propose to prepare 4,2' -anhydro-BR as a conformationally "friendly" analogue of BR with improved affinity towards IMPDH in general. Its corresponding bis(phosphonate) analogue should have a better affinity towards IMPDH Type II than BR derivatives. In Phase I, the new compounds will be evaluated for their inhibitory activity against IMPDH Type I and II, and cytotoxic activity against HT-29 cells. The most active compounds will be examined for their apoptosis inducing activity and antitumor activity in human colon carcinoma HT-29 growing as a subcutaneous model and as an orthotopic model to mimic metastatic colon cancer to liver, in athymic mice. In Phase II, sufficient amounts of the candidate compounds will be prepared for examining antitumor activity inother tumor models, toxicologic and pharmacological studies required for an IND application. PROPOSED COMMERCIAL APPLICATION: Ribavirin (antiviral) and mycophenolic acid (immunosuppressant) are clinically used drugs that express their activity through inhibition of inosine monophosphate dehydrogenase (IMPDH). New inhibitors of IMPDH, tiazofurin-and benzamide riboside adenine dinucleotide (TAD and BAD) analogues, were developed by us and showed potent activity against human colon and ovarian cancer. These compounds are potential drugs for treatment of colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: NOVEL HUMAN ONCOGENE STK15/BTAK/AURORA 2 Principal Investigator & Institution: Sen, Subrata; Assistant Professor; Div of Laboratory Medicine; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 26-SEP-2001; Project End 31-AUG-2005 Summary: (provided by applicant) We have cloned a novel human kinase encoding gene (STKI5/BTAKaurora2), harbored on chromosome 20q13 that is amplified/overexpressed in many different human tumor cell types (Sen et al, Oncogene 14:2195-2200; Zhoui Kuang, Zhong, Kuo, Gray, Brinkley and Sen. Nature Genetics 20:189-193, 1998). Over-expression of this gene induces abnormal centrosome duplication/distribution, aneuploidy and tumorigenic transformation in mammalian cells. Over expression of STK1 5 has been detected in about 50 percent of unselected primary colon tumors and gene amplification detected in about 12 percent of unselected primary breast tumors. Over all goals of this project include elucidating the STK1 5 pathway that is involved in maintaining genomic stability and induction of aneuploidy
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in normal and cancer cells respectively. We also propose to evaluate the patho-genetic significance of STK1 5 protein and STK1 5 interacting proteins in human colon cancer cells. The specific aims of this project are to: 1. Identify the interactions of STK1 5 kinase with its potential regulator and effector proteins through the G2-M phase of the cell division cycle. The results would help understand the role of these interactions in G2-MAnaphase progression of cells. 2. Investigate amino acid structural requirements and post-translational modifications required for a) STK1 5 sub-cellular localization including targeting to centrosomes, and b) binding to interacting proteins. Results would help elucidate the biochemical mechanisms regulating STK1 5 localization and their functional relevance. 3. Investigate the role of STK1 5 and its interacting proteins in the regulation of centrosome function and chromosomal stability in proliferating cells in vivo through co-transfection experiments with appropriate wild type and mutant expression constructs. The findings of these studies are expected to elucidate the pathway that involves STK1 5 in maintaining genomic stability as well as in activating changes leading to transformation of cells due to abnormally elevated expression of the gene. 4. Determine the expression profiles of STK15 kinase and its interacting proteins in colon cancer specimens of different histological grades and stages with or without chromosomal instability phenotypes. Results would help assess the diagnostic and prognostic significance of STK1 5 pathway in this cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: NOVEL STRATEGIES FOR THE IMMUNOTHERAPY OF COLON CANCER Principal Investigator & Institution: Reisfeld, Ralph A.; Professor/ Head; Scripps Research Institute 10550 N Torrey Pines Rd San Diego, CA 92037 Timing: Fiscal Year 2001; Project Start 08-MAY-2000; Project End 30-APR-2004 Summary: (Adapted from applicant's abstract) The overall objective is to construct and optimize novel human CEA-based DNA vaccines for the effective immunotherapy of colon carcinoma. The investigators will test the hypothesis that peripheral T cell tolerance to these tumor self-antigens can be overcome by DNA vaccines boosted by effective adjuvants designed to generate cytolytic T lymphocyte (CTLs) specific for CEA epitopes expressed as MHC class I complexes on colon carcinoma cells. Emphasis will be on optimizing antigen processing and presentation in mouse models either transgenic for CEA or double transgenic for CEA and HLA-A2.1Kb. Their aim is to use such models for optimization of vaccine by antibody-cytokine fusion proteins and to investigate basic concepts such as mechanisms of T cell co-stimulation, generation of tumor-specific CTLs and T memory cells and establish principles for adoptive immunotherapy. The specific aims designed to achieve these objectives are: 1) construction of optimal human CEA-specific DNA vaccines containing first the entire CEA gene and then minigenes encoding specific CEA peptides with HLA-A*0201 anchor residues. Delivery of the vaccines by injction of naked KNA or orally by galvage using attenuated strains of either Salmonella typhimurium or Listeria monocytogenes; 2) optimization of antigen processing in the 20S proteasome and presentation by using ubiquitinated versions of the entire CEA gene, minigenes encoding several CEA nonapeptides organized as as a string of beads or direct targeting of single CEA or repeat epitopes to the endoplasmic reticulum; 3) achievement of optimal adjuvanticity using either unmethylated CpG dinucleotide motifs or CD40 Ligand/Trimer coexpression; and 4) determination whether antibody-IL2 fusion proteins can effectively boost DNA vaccines to achieve optimal, long-lived tumor-protective immunity, as well as eradicate established metastases, and identification of immunological mechanisms
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involved in generating tumor-specific CTLs and T memory cells. The achievement of this proposal's objectives should lead to the design of effective DNA vaccines based on rational immunological principles that may ultimately lead to the improved treatment of colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: OBESITY, HYPERINSULINEMIA AND COLON CANCER Principal Investigator & Institution: Fleming, Sharon E.; Professor; Nutritional Scis & Toxicology; University of California Berkeley Berkeley, CA 94720 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): There is substantial epidemiological evidence that being overweight or obese increases risk of colonic cancer. The data are stronger for men than for women and stronger for cancer of the left than right colon, with an overall doubling of risk. Data from two studies using Zucker rats support this notion. Diabetes is associated also with increased risk of colonic cancer, and this is directly supported by one animal study. Insulin and insulin-like growth factors are known to affect biological processes such as proliferation and apoptosis in vitro. Since obesity and hyperinsulinemia often co-exist in animal models and in humans, it has been difficult to determine their separate contributions to disease risk. In this application, we hypothesize that hyperinsulinemia is responsible for increased susceptibility of the overweight and obese to colonic cancer. We will use C57BL/6J mice to determine whether obese animals are more susceptible than their lean littermates to carcinogeninduced colon tumorigenesis. Initially, this will be done by comparing responses of wild-type versus Lepob mutants. In a second study, responses of lean, wild-type mice with normal weight and insulin levels will be compared to responses of mice that are both obese and hyperinsulinemic (induced by feeding a diet high in coconut oil) or hyperinsulinemic but not obese (induced by feeding a high-fructose diet). To determine the contribution that obesity in the absence of hyperinsulinemia makes to colonic tumorigenesis, plasma insulin levels will be reduced in Lepob mutants using metformin. Susceptibility to colonic tumorigenesis will be assessed by measuring aberrant crypt foci, crypt cell proliferation, and tumor incidence and multiplicity. We expect that hyperinsulinemia will stimulate colon tumorigenesis, whereas obesity in the absence of hyperinsulinemia will not. These studies will provide new knowledge that will be used to support a follow-up R01 application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ONTARIO REGISTRY FOR STUDIES OF FAMILIAL COLON CANCER Principal Investigator & Institution: Gallinger, Steven; Cancer Care Ontario 620 University Ave, Ste 1500 Toronto, Timing: Fiscal Year 2001; Project Start 30-SEP-1997; Project End 30-JUN-2002 Summary: (Applicant's Description) The general objective of this application is to develop a population-based colorectal cancer (CRC) family registry resource, with epidemiologic data and a biologic tissue bank, from CRC patients in Ontario, Canada. The registry will be a contributor to the consortium of such registries planned by the National Institutes of Health (NIH) that will be used for epidemiologic studies, primary prevention trials, gene discovery; for the investigation of gene environment interactions; and for the evaluation of surveillance protocols and treatment interventions in high risk CRC families as part of a Co-operative Agreement with other family registries. This
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objective will be met by building on existing infrastructure and experience developed by co-investigators participating in the activities of the previously awarded Co-operative Family Registry for Breast Cancer Studies (CFRBCS), with which the CRC registry proposed here will be integrated. Further, the proposed Co-operative Family Registry for Colon Cancer Studies (CFRCCS) will take advantage of established resources, in particular the Ontario Cancer Genetics Network (OCGN) and the population-based Ontario Cancer Registry (OCR). The applicant plans to compile family history data for all eligible CRC cases in Ontario who will serve as probands, and family history information will be used to define cohorts of high risk according to the Amsterdam criteria and intermediate risk and sporadic cases and their families. Epidemiologic data, CRC treatment data and biologic tissues will be obtained from all high and intermediate risk probands and their families, from a random sample of sporadic cases (and a subsample of their families), and from population controls and a sample of their families. The frequency and nature of mutations in genes involved in hereditary predisposition to colon cancer in high and intermediate risk families will be determined. Molecular diagnostic testing will be performed on specimens from probands in these risk groups. The populations with hereditary predisposition to CRC identified by these activities will be potential participants in trials that evaluate new prevention and therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: PHASE III COLON CANCER PREVENTION TRIAL Principal Investigator & Institution: Meyskens, Frank L.; Professor of Medicine; Medicine; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by the applicant): The long-range objective of our work is to develop safe and effective drugs to prevent colon cancer, which is the fourth most common incident cancer in America with over 58,000 people dying of the disease in the year 2000. Our specific aims in this application are: 1.To conduct a randomized, doubleblind placebo-controlled phase III clinical chemoprevention trial of the combination of DFMO plus sulindac to decrease the rate of new adenomatous polyp formation. 2. To correlate the effects of the combination on polyamine and prostaglandin contents in the flat mucosa to the rate of adenoma formation. 3. To determine the rate of side effects in patients randomized to the combination therapy over the course of the intervention. The major objectives of this investigation are to reduce the recurrence rate of adenomatous colonic polyps without producing toxicity greater than that seen in the placebo group. The overall goal of our work is to develop safe combinations of chemoprevention agents that can be used in the practice setting and complement current surveillance efforts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHYSICAL ACTIVITY, ENERGY BALANCE, AND COLON CANCER RISK Principal Investigator & Institution: Matthews, Charles E.; Assistant Professor; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, SC 29208 Timing: Fiscal Year 2002; Project Start 29-SEP-2002; Project End 31-AUG-2007 Summary: There is consensus that low physical colon cancer in humans, particularly among However, the precise mechanism(s) of action established. Although initial evidence indicates
activity (PA) levels increase the risk of individuals with elevated adiposity. for these associations have not been a role for inflammatory markers (e.g.,
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prostaglandin-E2) among individuals with low PA or high levels of adiposity, simple descriptions of the patterns of cell proliferation and apoptosis, or markers of these processes, across PA levels are not available. Accordingly, the first aim of this proposal is to develop and refine hypotheses concerning the biologic mechanisms through which PA reduces risk for colon cancer by: (a) evaluating the independent and combined associations of physical activity/fitness, adiposity, and metabolic predictors (blood glucose, triglycerides) of colon cancer risk in the Aerobics Center Longitudinal Study (Dallas, TX) using a nested-case control design (N=600), and (b) evaluating the independent and combined associations of PA and adiposity on biomarkers for colon cancer associated with inflammation (cyelooxygenase-2), cell proliferation (mib 1), and apoptosis (bax, bak, bcl2) in cross-sectional analyses of the Markers of Adenomatous Polyps II Study (N=200, Columbia, SC). Results from these analyses will be used to select up to 10 biomarkers for evaluation in a longitudinal pilot study. The second aim is to quantify the effect of changes in PA levels on selected biomarkers in a randomized trial (N=50, intervention vs. usual care) among adults not meeting current PA recommendations. Intervention participants will receive a 12-month home-base walking intervention based on Social Cognitive Theory that includes monthly phone contact with a health educator. Potential mediators and moderators of behavior change will be quantified (e.g., self-efficacy, social support). PA goals for the intervention group will be to walk briskly at least 5 times per week for 40-45 minute per day (1125 kcal/wk). Outcome biomarker measures will be obtained via rectal biopsy at baseline and 12months. In summary, the series of investigations outlined in this proposal will examine the independent and combined effects of PA and energy balance (adiposity) on colon cancer and adenomatous polyp outcomes, and relate these findings to parallel analyses on tissue biomarker outcomes describing the biologic mechanisms linking PA and energy balance to colon cancer risk. This work will extend our understanding of the biological mechanisms underlying these causal relationships. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: PILOT--ANGIOPOIETINS ANGIOGENESIS
1
&
2
IN
COLON
CANCER
Principal Investigator & Institution: Ellis, Lee M.; Professor of Surgery & Cancer Biology; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 16-JUL-2001; Project End 31-DEC-2005 Summary: Angiogenesis is driven by specific factors that lead to endothelial cell (EC) proliferation, invasion, survival, and differentiation. The activity of pro-angiogenic molecules must exceed that anti-angiogenic molecules to induce neovascularization. In addition to the induction of angiogenesis, tumors must support the vasculature under adverse environmental conditions (hypoxia or low Ph). For ECs to survive in these conditions, tumors must secrete EC "survival factors". Vascular endothelial growth factor (VEGF), an important angiogenic factor in colon cancer progression and metastases, has also been shown to be an EC survival factor. Recently, the angiopoietin (Ang) family of ligands has been found to be important in tumor angiogenesis. Ang-1 and Ang-2 both bind to the specific EC receptor Tie-2; however, their biologic effects are antagonistic. Ang-1 binds to the Tie-2 receptor, initiating activity of the tyrosine kinase activity of this transmembrane receptor. Activation of the Tie-2 receptor leads to EC stability, and inhibits EC apoptosis. Alternatively, Ang-2 binds to the Tie-2 receptor, but antagonizes the effect of Ang-1, leading to EC destabilization and apoptosis. The coordinated induction of Ang-1, Ang-2, and VEGF has been sown to be important in the induction of tumor angiogenesis. The overall goal of this proposal is to determine the
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function and regulation of the angiopoietins in colon cancer angiogenesis. Specifically, we will determine: 1) the relative expression of Ang-1 and Ang-2 in human colon cancer specimens and normal mucosa. 2) the effect of over-expression of the Ang-1 or Ang-2 on tumor growth, angiogenesis, and metastases in a murine model of human colon cancer. 3) the effect of over-expression of Ang-1 and Ang-2 on tumor permeability. 4) the effect of conditioned medium from colon cancer cells, pericytes, and non-malignant cells on Ang-1 and Ang-2 expression in ECS. The significance of this pilot project is that a more thorough understanding of the angiopoietins in "stabilizing" and "destabilizing" the tumor neovasculature may lead to new therapeutic strategies or identify targets for imaging the altered neovasculature when exposed to anti- angiogenic agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: PILOT--GENOMIC INSTABILITY AND GENE SILENCING IN COLON CANCER Principal Investigator & Institution: Ashktorab, Hassan; Howard University 2400 6Th St Nw Washington, DC 20059 Timing: Fiscal Year 2001; Project Start 13-JUL-2001; Project End 30-APR-2006 Summary: Colorectal carcinoma (CRC) is the most common gastrointestinal malignancy, affecting about 160,000 individuals per year in the U.S. and the rate of CRC is 1.5 times higher in African Americans than in Caucasians. Several lines of evidence generated by epidemiological, animal and in vitro studies suggest a pathway in the development of colon cancer. The biomarkers of neoplastic transformation, which have a predictive value as antecedents of malignancy include: changes in biomarkers of neoplastic transformation, which will have a predictive value as antecedents of malignancy include: changes in expression of genes of cell cycle regulatory proteins (p16) and gene mutations (DNA mismatch repair genes). Methylation of the DNA is part of the regulation of gene productions in the CpG island. Genes can be turned off by methylation and in some cases turning off important genes (e.g. tumor suppressor genes) can be suicidal to cells. We postulate that micro- satellite instability (MSI) and/or silencing of p16, a tumor suppressor gene, which is known to modulate cellular proliferation in colonic instability (MSI) and/or silencing of p16, a tumor suppressor gene, which is known to modulate cellular proliferation in colonic mucosa, may alter chromosome behavior in the process of neoplastic transformation. The important role of methylation and MSI in the pathogenicity of colon cancer has been increasingly recognized.. Identification of errors in DNA replication that can be detected by MSI is part of the neoplastic progression and provides a unique opportunity to study the development of colonic neoplasia. In this proposal we plan to conduct experiments on normal and colon cancer tissue resected from subjects (n=120) over the past 3 years. Tissue will be obtained retrospectively from archival specimens of CRC patients diagnosed at Howard University and Johns Hopkins University to determine chromosome imbalance and gene alterations. Five microsatellite loci will be measured by MSI and, by immunohistochemistry in tissue samples. Non-parametric statistical tests will be applied to determine the correlation between histological changes (degree of dysplasia, expansion of the cryp proliferative zone) and to determine the correlation between histological changes (degree of dysplasia, expansion of the crypt proliferative zone) and changes in the expression of biomarkers of neoplastic transformation (p16 methylation and MSI). This has not yet been well studied, therefore we are carrying out this pilot project to better define the prevalence of MSI in cancers from African American persons. The purpose of this collaborative proposal is to examine the effect of gene methylation such as p16 and MSI in the pathway of neoplastic transformation in
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patients with a history of resected colon cancer compared with changes in similar markers in mucosal biopsies in normal controls. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: PRECLINICAL EVALUATION OF BLACK TEA EXTRACTS Principal Investigator & Institution: Evans, David A.; Wellgen, Inc. C/O Rutgers UnivCaft New Brunswick, NJ 08901 Timing: Fiscal Year 2002; Project Start 25-SEP-2002; Project End 31-MAR-2003 Summary: (provided by applicant): Many claims suggesting health beneficial effects of black tea and its components exist in the scientific and lay literature. One such presumed health benefit of tea consumption is decreased risk of cancer. In the United States, each year there are 93,800 new cases and 47,700 deaths due to colon cancer. Among cancer diseases, the evidence for the importance of diet and nutrition is strongest for colon cancer. Therefore, there is a need to find ways to prevent this disease. The overall goal of WellGen, Inc. is to find and develop value-added dietary supplements using sound scientific information. This proposal, entitled "Preclinical Evaluation of Black Tea Extracts" is consistent with our primary goal. Scientific information will be generated in model systems before evaluation in humans. Based on this knowledge, black tea dietary supplements will be developed. Black tea extracts, theaflavin mixtures derived from green tea, and purified chemicals that occur in black tea will be evaluated in three mouse models. All compounds will be evaluated in two mouse ear inflammation assays. Selected compounds will be evaluated in a Min mouse model for colon cancer. The following specific aims are designed to accomplish the overall goal for the 6 months of the Phase 1 study. 1. Prepare standardized, modified theaflavin extracts from decaffeinated green tea 2. Prepare from catechin precursors the following pure compounds: theatlavin(TF-1), theaflavin-3-monogallate and theaflavin-3'-monogallate ( the combination of these two isomers are referred to as TF2), and theaflavin-3,3'-digallate (TF-3) (200 mg each to evaluate in mouse ear models) 3. Evaluate decaffeinated black tea extract, theaflavin extracts and four pure theaflavin compounds in the 12-O-tetradecanoylphorbol-13 acetate (TPA) and arachidonic acid (AA) induced mouse ear models. 4. Evaluate decaffeinated black tea extract and theaflavin extracts in a Min mouse model 5. Conceptualize and analyze prototype product (dietary supplement) development strategy 6. Plan for biomarker endpoint colon cancer clinical studies Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PREDICTING TUMOR RESPONSE TO FLUOROURACIL WITH PET Principal Investigator & Institution: Bading, James R.; Radiology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, CA 90033 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2003 Summary: There is a substantial need to develop accurate methods for predicting individual response to chemotherapy. Imaging of radiolabeled chemotherapeutic drugs with PET provides one approach to this problem. However, the usefulness of PET with drugs that are rapidly broken down in vivo, such as 5-fluorouracil (FU), is limited by the inability of the methodology to directly identify the molecular association of the radiolabel. Our long range objective is to develop PET as a tool for predicting response to chemotherapy and individualizing regimens for treating neoplastic disease. Our intermediate range objective is to develop clinically-practical PET techniques for predicting tumor response to FU. In order to be effective, FU must be taken up by tumor
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cells and anabolized to fluoronucleotides, which in turn interfere with DNA and RNA synthesis. Investigators at Heidelberg, Germany, recently reported positive correlation between tumor response to FU and tumor retention of radiolabel from [18F]FU as measured in PET in 17 patients undergoing treatment for metastatic colon cancer. While very promising, this study did not address the influence of recirculating, labeled catabolites of [18F]FU on the PET images, and the imaging technique used provides little information about the kinetics of FU in tumors. We are developing a new approach in which biomodulation is used to create an in vivo imaging technique capable of measuring tumor transport and metabolism of FU per se. Specifically, we pretreat with ethynyluracil (EU), a potent inhibitor of FU catabolism, to prevent degradation of [18F]FU and thereby improve the sensitivity of PET to those aspects of FU pharmacokinetics most closely related to tumor response. We have shown in preclinical studies with a rat colon tumor model that cellular uptake and anabolism of FU can be accurately measured by mathematical modeling of data obtained with our "PET/[18F]FU+EU"technique. The specific aims of the proposed study are (1) to evaluate our "PET[18F]FU+EU" technique for predicting tumor response to a form of therapy in which the technique is very closely related, viz., FU modulated by EU ("FU+EU"); and (2) to repeat the Heidelberg study "PET/[18F]FU") in a larger group of patients with colon cancer. The timeliness of Aim 1 is enhanced by current Phase II clinical trials of FU+EU and new indications of the importance of FU catabolism as a mechanism of tumor resistance to the drug. While PET and [18F]FU may provide information related to thymidylate synthase (TS), the primary target of FU, the imaging techniques does not measure TS inhibition directly. In the proposed study, TS concentration in tumor, a known correlate of tumor response, will be measured via tumor biopsy prior to therapy. Multiple regression analysis will be used to evaluate combination of parameters derived from PET and ex vivo TS assays as predictors of tumor response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: PREDICTION IN FAMILIAL COLORECTAL CANCER Principal Investigator & Institution: Parmigiani, Giovanni; Associate Professor; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Identifying and counseling individuals at high risk of colon cancer because of their family history is complex and increasingly common. Prediction algorithms that fully exploit laboratory-based biological knowledge of inheritance mechanisms and other characteristics of susceptibility genes can contribute importantly to improved screening, prevention, and genetic testing, and to the design of health behavior interventions, cancer on studies, and genetic epidemiology studies. Mendelian risk prediction models make efficient use of laboratory-based information, and have been successfully used in a number of prevention, clinical, and research activities associated with the BRCA genes. The goals of this project are to develop (aim 1), and validate both retrospectively and prospectively (aim 2), a Mendelian risk prediction model for colon cancer susceptibility genes. The model will assist counseling of individuals at high risk of familial colon cancer, by providing accurate estimates of the probability that they carry a deleterious mutation of a colon cancer susceptibility gene, and of the probability that they subsequently develop cancer, based on family history. Syndromes considered will include HNPCC, FAP and the syndrome induced by the I1307K mutation of the FAP gene. Model training and validation will be based on a comprehensive elaboration of all evidence available, as well as data from four
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participating centers. Results from our study will make a significant contribution to colon cancer prevention by (a) promoting decision-making about genetic testing for susceptibility to colon cancer, via reliable individualized pre-test and post-test carrier probabilities; and (b) providing tools for identifying individuals at high risk of familial colon cancer. In addition, results from our study will also contribute to our understanding of genetic susceptibility to colorectal cancer by (a) developing reliable admission criteria for studies of gene characterization and gene environment interactions; (b) providing validated surrogate measures of genetic susceptibility for studies in which genetic testing is impractical or only partially performed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: PREDICTORS OF OUTCOME IN COLORECTAL CANCER Principal Investigator & Institution: Meyerhardt, Jeffrey A.; Dana-Farber Cancer Institute 44 Binney St Boston, MA 02115 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): In 2001, approximately 135,400 Americans are expected to develop colorectal cancer, and 56,700 individuals will die from the disease. Though 80% of patients present at a stage when all apparent diseased tissue can be surgically resected, up to 40% of these patients will suffer from recurrence. Depth of tumor invasion and nodal status are considered the most important predictors of recurrence, and are the primary factors used by clinicians in recommending to patients adjuvant therapy after surgery. However, there is considerable variation in the outcome of patients with colorectal cancer not explained by traditional prognostic factors. The candidate for this award will utilize databases from two large, randomized adjuvant therapy trials to study other prognostic factors on outcomes in colon and rectal cancer. Specifically, these databases provide an opportunity to study the influence of potential modifiable treatment and patient characteristics on short- and long-term outcomes in patients with potentially curable colon and rectal cancers treated with surgery and adjuvant therapy. The specific aims of this proposal are (1) to examine whether hospital surgical volume and hospital characteristics affect cancer recurrence, overall survival, and treatment-related toxicity in patients undergoing curative surgery and adjuvant therapy for stages II and III rectal cancer, and (2) to examine the impact of diet and lifestyle on colon cancer recurrence and survival. Completion of these projects will improve our understanding of how potentially modifiable factors affect outcomes in patients treated with curative surgery and standard adjuvant therapy. These projects will provide insight into dietary and lifestyle behaviors of patients with colon cancer and which behaviors impact outcomes. Finally, these projects will allow the candidate to gain invaluable experience in database analysis and clinical epidemiologic and health outcomes research. The candidate will complete a Masters in Public Health (MPH) degree and advanced courses at the Harvard School of Public Health during the first two years of the proposed award. The projects will be performed under the mentorship of Dr. Charles Fuchs, a well-established researcher in prevention and health services research. At the completion of the project, the candidate will have gained the experience to become an independent researcher in clinical epidemiologic and health outcomes research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PREDISPOSING/MODIFYING GENES IN HEREDITARY COLON CANCER Principal Investigator & Institution: Peltomaki, Paivi T.; Medical Microbiol & Immunology; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, OH 43210 Timing: Fiscal Year 2001; Project Start 17-AUG-1999; Project End 31-JUL-2002 Summary: (Adapted from investigator's abstract) Susceptibility to hereditary nonpolyposis colon cancer (HNPCC) is associated with germline mutations in five genes with DNA mismatch repair function. Previous studies have shown that these genes account for two-thirds of HNPCC kindreds meeting the international diagnostic criteria for the disorder and displaying microsatellite instability as a characteristic abnormality in tumors. The basis for cancer susceptibility is unknown in the remaining one-third of kindreds with microsatellite instability and in most families without this abnormality. Furthermore, in kindreds with detectable mutations and even with shared predispositions, the clinical phenotype varies a lot between and within individual families, the reasons for which are largely unknown. The broad objective of the present study is to identify genes and mechanisms associated with cancer susceptibility and phenotype determination in non-polypotic colon cancer. The detection of such genes is of prime importance given the fact that half the Western population is estimated to develop a colon tumor during their lifetime. Importantly, the progression of those lesions to cancer can be prevented by early intervention, and genetic markers of increased cancer risk are needed to define the cohorts who would be the first to benefit from such preventive measures. The Specific Aim 1 focuses on kindreds with nonpolyposis colon cancer in which mutations in the presently known HNPCC-associated DNA mismatch repair genes have been ruled out by sequencing. A genome-wide search is applied with the goal to identify novel genes associated with cancer predisposition in these kindreds. The Specific Aim 2 focuses on a unique series of families with shared predisposing mutations. The observation of clinical variation in the setting shared predisposition suggests the existence of additional phenotype determinants. The aim is to identify genes that might modify the clinical phenotype of HNPCC, taking advantage of association and linkage-based approaches in these genetically homogeneous subsets of HNPCC patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PREVENTION OF COLON CANCER BY AN AT2 RECEPTOR ANTAGONIST Principal Investigator & Institution: Tamura, Masaaki; Biochemistry; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2003 Summary: (provided by applicant): Epidemiological studies indicate that a majority of the cases of colorectal cancer are etiologically related to environmental factors. Carcinogenic xenobiotics are activated by phase I biotransformation enzymes. This biotransformation mainly occurs in the liver, but also in extrahepatic tissues. Cytochrome P4501A1, 1A2 and 2E1 (CYP1A1, lA2 and 2E1) are major catalysts in the bioactivation of a number of putative colorectal cancer procarcinogens such as polycyclic aromatic hydrocarbons, heterocyclic amines and N-nitrosoamines. Thus, control of biotransformation enzymes is a potential approach to prevent tumorigenesis in the colon. Recently, we were able to demonstrate that mice deficient in the angiotensin II (Ang II) subtype 2 (AT2) receptor gene are resistant to azoxymethane (AOM)-induced colon adenocarcinoma. AOM-stimulated CYP1A1, 1A2 and 2E1 protein
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induction in the liver of wild type mice is more significant than in AT2: receptordeficient (AT2-KO) mice. These preliminary studies suggest that Ang II-AT2 receptor signaling may function as a regulator of cytochrome P450 enzyme activities in the liver. Based upon our preliminary studies we hypothesize that 1) Ang II- AT2 receptormediated signaling is involved in the induction of carcinogen- metabolizing cytochrome P450s in the liver and/or colon epithelial cells, 2) attenuation of AT2 receptor function diminishes DNA adduct formation in the liver and colon epithelial cells, and thus 3) the Ang II-AT2 receptor-mediated signal is involved in the initiation of tumorigenesis in the colon. Accordingly, pharmacological attenuation of the AT2 receptor function prevents colon tumorigenesis. In this proposal we place our priority on the chemoprevention of AOM-induced colon cancer. Thus, we propose to determine the effect of blockade of the AT2 receptor function by the AT2 receptor- specific antagonist PD123319 in AOMinduced colon adenocarcinoma and to clarify the mechanism of low susceptibility to AOM in AT2-KO mice. These studies will clarify the role of the Ang II-AT2 receptor in colorectal tumorigenesis and will provide a totally new target for the chemoprevention of colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: PREVENTIVE ONCOLOGY ACADEMIC AWARD Principal Investigator & Institution: Alberg, Anthony J.; Epidemiology; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 07-SEP-1998; Project End 31-AUG-2003 Summary: (Applicant's Description) The proposed plan will provide me with a foundation for a long-term career in cancer epidemiology and prevention. The pathway outlined toward this goal is to gain proficiency in molecular epidemiology, which holds promise to advance our knowledge of both cancer etiology as well as cancer prevention, adding to my established skill in epidemiologic methods. A two-pronged approach of education and research is proposed. The educational plan is designed to: 1) expand my knowledge of molecular epidemiology and 2) enhance my teaching and communication skills. The former goal will be addressed through course work, discussion-oriented forums, and be reinforced by the research program. Toward the latter goal, I will participate in teaching classes on epidemiologic methods and cancer epidemiology. I will also work in community setting to enhance skills in communicating with decisionmakers. The research plan consists of three studies with a focus on colon cancer. Phase 1 is a prospective cohort study of cigarette smoking in relation to the risk of colon cancer. Phase 2 is a nested case control study to evaluate the relationships of cigarette smoking, diet, and polymorphisms in genes that encode carcinogen metabolizing enzymes in relation to colon cancer risk. Phase 3 is a cross-sectional study of the prevalence of lifestyle practices and cancer prevention behaviors that will lead to the development of a cancer control plan. The results of this research program, while contributing to our knowledge of the etiology of colon cancer, will be applicable susceptible subgroups of the population who may be at greatest risk. By strengthening my background in molecular epidemiology, the proposal plan will build upon previous experience in cancer epidemiology and prevention and will enable me to engage in a broad range of research geared toward the prevention of cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PREVENTIVE ONCOLOGY AWARD Principal Investigator & Institution: Kinney, Anita Y.; Associate Professor; None; University of Utah 200 S University St Salt Lake City, UT 84112
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Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: A five-year program integrating research, education, and teaching to develop skills in preventive oncology is proposed. This award will provide the applicant with intensive training under expert guidance of scientists in the field. The specific aims of the application are (1) to enhance the candidate's clinical and research training to include the study of the effects of targeted psychosocial factors on colon cancer-related outcomes; (2) to acquire in-depth training in psychosocial methods, bioethics, and health policy at the intersection of epidemiology and the behavioral and biological sciences; and (3) to gain experience teaching about cancer prevention and issues related to genetic testing of cancer. The training plan includes (1) course work, (2) research, (3) teaching, (4) participation in seminars, and (5) clinical practica in cancer genetics. The research plan is multifaceted and designed to help the candidate develop her goals and provide practical experience in conducting biobehavioral cancer prevention research. The research plan consists of two projects: "Social Support and Colon Cancer in Blacks and Whites" (Project 1) and "Behavioral and Psychosocial Issues Related to Screening Testing for Familial Adenomatous Polyposis" (Project 2). Project 1 uses data from a funded population-based case -control study of colon cancer in blacks and whites. This research will help elucidate mechanisms by which social support and social networks influence various colon-cancer related outcomes. Project 2 is designed to examine factors related to uptake of colonoscopic screening and genetic testing among adults and children at extreme risk for colon cancer. The research activities along with advanced studies of genetics, bioethics, and health policy, will provide the expertise needed for a career as a successful, independent investigator. Dr. Kinney's long-term goal is to develop a program of research in cancer prevention utilizing an interdisciplinary approach. This goal will be accomplished by being in a faculty role at an academic health science center. The University of Utah is a major academic institution with many distinguished scientists, and offers an excellent environment for Dr. Kinney to develop her skills and gain additional expertise to accomplish her goals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: PROFILING OF ALTERNATE MRNA SPLICING IN CANCER Principal Investigator & Institution: Srinivasan, Subha; Jivan Biologics, Inc. 733 Allston Way Berkeley, CA 94710 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JAN-2004 Summary: (provided by applicant): The primary objective of this proposal is to demonstrate the feasibility and applicability of high-throughput profiling of alternate splice mRNA variants of five selected genes -CD44, CD46, ErbB, Muc1 and VEGF - in colon cancer detection and staging. The most common approach towards molecular profiling has been comparison of gene expression profiles using cDNA, PCR, tissue and oligonucleotide arrays. The complete sequence of the human genome has revealed approximately 35,000 genes, far less than the 100,000 or so proteins that account for the complexity of human biology. One explanation for this apparent anomaly is alternate splicing of mRNA. Alternate splicing of genes will have a profound impact in the discovery and validation of druggable targets and diagnostic biomarkers, e. g., in cancer (NCI).There is a dire need for high-throughput technologies capable of characterizing all mRNA variants within a biological sample. Profiling the relative variation in mRNA splice variants in tissues offers an additional level of resolution, complementing conventional gene expression analysis. This is an innovative new approach that promises to have the scalability of gene-based arrays combined with the sensitivity of proteomics-based molecular profiling. Jivan Biologics is developing a highly sensitive
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and scalable process, TransExpress TM that uniquely integrates microarray technology with computational biology and molecular biology techniques for discovery, full-length stitching and measurement of differential expression of alternately spliced forms of genes. The key personnel on this project will be Dr. Subha Sinivasan, Principal Investigator, and Jonathan Bingham, both of whom have extensive industry experience in genomics, microarray / gene chip technology and bioinfomatics. Jivan will also avail of consulting services from Dr. Manny Ares (UCSC) and Dr. Doug Black (UCLA), preeminent academic scientists in mRNA alternate splicing. The specific aims for SBIR Phase I are: (1) to determine the conditions to optimize Transexpress TMto profile mRNA splice variants in normal and neoplastic colon tissue samples, and (2) to obtain consensus mRNA variant profiles for normal and neoplastic colon tissues, by optimizing oligonucleotide probe selection. The success of this feasibility study will be depend on obtaining a significant reduction in the variation in intensities among constitutively expressed oligonucleotides for the same gene, and p-values of less than 0.01 for profiles from normal versus cancer colon tissues. The methodology used in this project comprises: (1) proprietary design, synthesis and spotting of aminelabeled oligonucleotides on glass slides, (2) hybridization of these microarrays with cy3-1abeled cRNA from 25 normal and 50 cancer colon tissue samples, and (3) proprietary computational analysis to stitch together and determine the relative expression levels of mRNA alternate splice variants in normal versus colon cancer tissues. These technologies will have both commercial and academic utility, consistent with the research interests of the Cancer Diagnosis Program (CDP) of the Division of Cancer Diagnosis and Treatment at the National Cancer Institutes (NCI). Upon successful completion of this project Jivan will use similar approach to a much larger set of genes and variants to create oligobased mRNA signatures for different stages of colon cancer as well as cancers in other sites. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: PROSPECTIVE STUDIES OF DIET AND CANCER IN MEN AND WONEN Principal Investigator & Institution: Willett, Walter C.; Professor and Chairman; Nutrition; Harvard University (Sch of Public Hlth) Public Health Campus Boston, MA 02460 Timing: Fiscal Year 2001; Project Start 23-AUG-1991; Project End 31-MAR-2006 Summary: (provided by Applicant) This proposed Program will use prospectively collected dietary data and frozen plasma and DNA specimens to address a series of hypotheses regarding major cancers in men and women. In addition, these nutritional and genetic exposures will be examined in relation to specific molecular characteristics of tumors. The cancers to be studied are those of the prostate, colon and rectum, bladder, lung, kidney, and ovary. This Program Project supports, and depends on, the continued follow-up of 51,529 men who completed an extensive dietary questionnaire first in 1986 and again in 1990, 1994, and 1998 (the Health Professional?s Follow-up Study, HPFS), and is also closely linked to the Nurses? Health Study (NHS) of 121,700 women. The Program Project has already contributed substantially to information on diet and cancers of the breast, prostate, colon, and bladder. The proposed continuation will extend and refine observations from the first twelve years of follow-up and will also address new hypotheses related to both cancer incidence and survival. Project 1 will examine dietary (lycopene, calcium, and N-3 fatty acid intakes) and other predictors of prostate cancer incidence in relation to risk of PSA relapse among men with apparently successful treatment for localized prostate cancer. In addition, a series of dietary and
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hormonal factors will be related to specific characteristics of incident cancers, including expression of PTEN and COX-2 and markers of angiogenesis. Project 2 will address hypotheses relating intakes of folic acid, calcium and red meat and plasma levels of IGF1 and its binding proteins to risks of both colorectal cancer and adenomas. Interactions with germline polymorphisms and relationships with specific molecular tumor characteristics will be examined. Project 5 will examine dietary and related risk factors for bladder cancer in both men and women. Exposures will include intakes of cruciferous vegetables and total fluids, and biochemical indicators of selenium and arsenic exposure. Interactions with polymorphisms in carcinogen metabolizing genes and specific association with p53 expression in tumors will also be examined. Project 4 pools data from all eleven major published prospective studies of diet and cancer. Precise and unique information has already been obtained for breast, lung and colon cancers, and the proposed work will extend analyses to cancers of the pancreas and ovary. These highly interrelated studies that integrate dietary factors, established nondietary risk factors, endogenous hormone levels, genetic susceptibility, and molecular characteristics of tumors, will contribute importantly to the understanding and prevention of the major cancers of men and women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: PROSTATE CANCER GENETICS: LINKAGE ANALYSIS & GENE ENVIRONMENT INTERACTION Principal Investigator & Institution: Witte, John S.; Professor; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001 Summary: Colon cancer is the second leading cause of cancer mortality among adult Americans, accounting for 150,000 new cases and 70,000 deaths annually in the U.S. population. Each American carries a 7% lifetime risk of developing colon cancer. An essential feature of colon cancer, which carries the promise that colon cancer can be prevented in the population, is that colon cancer arises from a precursor, the adenomatous colon polyp. A pilot project is in progress to identify and to collect blood from 300 sib pairs in which both sibs are known to have in the present or to have developed in the past a colon neoplasm (either an adenomatous colon polyp or a colon cancer). After the DNA from the blood samples has been typed for marker loci spanning the human genome, the data will be analyzed to identify one or more major genes that predispose to the formation of colon polyps, and hence the existence of colon adenoma susceptibility alleles. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROTEIN KINASE C AND COLON CARCINOGENESIS Principal Investigator & Institution: Fields, Alan P.; Professor and Director; Pharmacology and Toxicology; University of Texas Medical Br Galveston 301 University Blvd Galveston, TX 77555 Timing: Fiscal Year 2001; Project Start 02-APR-1999; Project End 31-JAN-2004 Summary: Colon carcinogenesis is a complex, multi-step process involving progressive changes in intestinal epithelial cell proliferation, differentiation and programmed death. Our long-term goal is to understand the role of protein kinase C (PKC) isozymes in intestinal epithelial cell biology and colon carcinogenesis. Several lines of evidence suggest that the PKC betaII isozyme (PKC betaII) is involved in colon carcinogenesis. First, PKC betaII levels and activity are elevated in colon carcinomas compared to
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normal colonic epithelium. Second, PKC betaII is involved in colon carcinoma cell proliferation in vitro. Third, components of a high fat diet can potently stimulate intestinal epithelial cell PKC betaII activity and promote colon carcinogenesis. Based on these findings, and our preliminary studies, we hypothesize that PKC betaII is directly involved in colon carcinogenesis. To directly test this hypothesis, we developed transgenic mice that express elevated PKC betaII levels in the intestinal epithelium. In preliminary studies, these mice exhibit evidence of colonic epithelial hyperproliferation and an increased susceptibility to carcinogen-induced colon cancer. In this application we propose four specific aims to: 1) characterize three transgenic PKC betaII lines for transgene copy number, tissue distribution, expression level and activity of the PKC betaII transgene, and for changes in intestinal epithelial cytokinetics; 2) assess whether transgenic PKC betaII mice exhibit increased susceptibility to carcinogen-induced colon cancer; 3) determine whether a high fat diet enhances the susceptibility of transgenic PKC betaII mice to colon cancer; and 4) determine whether elevated PKC betaII expression synergizes with loss-of-function mutation of the APC tumor suppressor gene in promoting intestinal tumorigenesis in the APCmin mouse model. These studies will allow the first direct analysis of the role of PKC betaII in colon cancer in two relevant animal models of the human disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: RADIOIMMUNOTHERAPY AND MICROHETEROGENEITY Principal Investigator & Institution: Welt, Sydney; Sloan-Kettering Institute for Cancer Res New York, NY 10021 Timing: Fiscal Year 2001; Project Start 21-FEB-2001; Project End 31-DEC-2001 Summary: The treatment of advanced colon cancer with available modalities has been consistently unsuccessfully, partially due to the lack of reagents with sufficient antitumor activity to impact on survival. Recently, antibody based therapies have shown significant anti-tumor effects in solid-tumor patients either as single agents or in combination with chemotherapy. Three humanized antibodies (huA33, huF19, huS193) reactive with colon cancer cells have been identified as promising tumor targeting agents and the feasibility of patient re-treatment has been demonstrated. This proposal addresses the limitation of single antibodies as immuno or radiotherapeutic agents in the treatment of cancer. Due to heterogeneous antigen expression, micro-distribution, leading to under-treated tumor regions and ultimately to resistance to treatment. The theme of this proposal is that combinations of antibodies and small-molecular -weight constructs may improve uniformity of antibody binding and therapeutic efficacy; and therapeutic isotopes with the proper energy and emission path length for each antibody/construct will increase the radiolysis of tumor cells. The aims are to analyze, by quantitative radiosimetry, resected tissues from patients treated with combinations of radiolabeled antibodies/constructs; and to determine toxicity and efficacy of antibody combinations in phase I and II studies. Each of the two components of colon cancer, carcinoma cells and the supporting stromal cells, can now be effectively targeted with these antibodies. A truly uniform radiation field may be achieved in tumors with combinations of antibodies/constructs combinations to tumors, pharmacokinetics, radio- isotope selection, dosimetry modeling, and definition of toxicity profiles in phase I studies will identify the optimal reagent combination for immuno- and radioimmunotherapy of colorectal cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION BY KRUPPEL LIKE FACTOR IN THE COLON Principal Investigator & Institution: Tseng, Chi-Chuan C.; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, MA 02118 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Colorectal carcinogenesis is a multi-step process including both the activation of oncogenes and the loss of tumor suppressor genes. Most of the neoplastic lesions in the colon arise through the progression from normal to hyperproliferative epithelium, adenoma and carcinoma, It is hypothesized that cellular hyperproliferation resulting from either spontaneous mutation or increased in intestinal proliferation leads to clonal expansion and carcinogenesis. Although multiple genetic mutations have been described, the molecular events governing intestinal hyperproliferation is unknown. Recently, an eukaryotic zinc finger protein, gut-enriched Kruppel-like factor (GKLF/KLF4), has been identified to be an important factor in controlling growth arrest. Our laboratory has shown that GKLF gene expression is reduced in colon cancer tissue and that constitutive expression of an antisense GKLF DNA in a colon tumor cell line results in cell hyperproliferation. These data suggest that down-regulation of GKLF may lead to uninhibited cell growth. Furthermore, GKLF mRNA levels increased as colonic epithelium acquired more differentiated phenotype. We hypothesize that up-regulation of GKLF is essential for colonic epithelium to become differentiated and that down-regulation of GKLF will render colonic cells to become hyperproliferated and ultimately neoplastic transformation. The precise physiological function of GKLF in the colon is not clear and its up- and down-stream targets are currently unknown. The aims of the current study are: (1) to elucidate the physiological properties of GKLF by examining the effect of constitutive overexpression of sense, antisense or dominant-negative mutant GKLF DNA on cell growth and differentiation in normal colon epithelial; adenoma; and cancer cell lines; (2) to investigate the role of GKLF in cell cycle progression by examining its effect on cyclins, cyclin-dependent kinases (cdks) expression, and on transcriptional regulation of the cyclin D1 gene; and (3) to examine molecular mechanisms governing basal transcription of the GKLF gene as well as vit D3- or interferon-gama-promoted GKLF expression. Collectively, the information gained from this proposal will add to our understanding the contribution of GKLF to growth, differentiation, and malignant transformation of the colonic epithelial cells. Ultimately, if the GKLF down-regulation process can be manipulated, it may be possible to use inhibitors of this process for chemoprevention of cancer formation in the gastrointestinal tract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF CDX GENE EXPRESSION IN COLON CANCER Principal Investigator & Institution: Suh, Eunran; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 05-APR-1999; Project End 31-JAN-2003 Summary: This is the firs application from a new investigator with the overall objective to investigate the regulation of caudal-related homeobox (CDX) proteins in normal colon and colorectal cancer. CDX1 and CDX2 are transcription factors that are involved in regulation of proliferation and differentiation of the intestinal epithelial cell. Additionally, expression of replacement of CDX gene expression in colon carcinoma cell lines dramatically inhibits cellular proliferation by cell cycle arrest in G1. Thus, altered regulation of CDX genes in colonic epithelial cells is involved in the development of the neoplastic phenotype. Therefore, this proposal is based on the hypothesis that an
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understanding of the regulation of CDX genes in both normal and neoplastic cells will elucidate pathways that control the phenotype in cancer cells. The goal of this project is to elucidate the normal regulation of CDX1 and CDX2 and to determine changes that occur in the colonic neoplasia. Preliminary are presented that demonstrate variable of CDX genes in colorectal cancer cell lines and that this differential expression is regulated the level of gene transcription. To accomplish this goal, four specific aims are proposed: 1) To elucidate the transcriptional regulation of the human CDX1 gene in normal and neoplastic colonocytes using DNase I hypersensitivity. mapping and transfection and DNA-protein interaction studies. Preliminary data shows that there is a specific hypersensitive site in a cell line that expresses CDX1 that is absent in nonintestinal cell lines and intestinal cell lines and intestinal cell lines that do not express CDX1. The function of this site will be explored and the remainder of the gene will be studied for additional sites. 2) To elucidate the transcriptional regulation of CDX2 in normal and neoplastic tissue. Similar to CDX1, we have mapped and characterized and characterized the CDX2 gene. Transfection studies suggest that elements for directing intestine-specific expression are outside the immediate upstream region of the gene. DNase I hypersensitive site analysis will also be employed to identify potential regulatory regions. 3) To study the regulation of CDX genes in transgenic mice. These studies will validate the function of regulatory elements identified in Aims 1 and 2 in the whole animals. 4) To examine cellular signaling pathways that regulate CDX genes in colon cancer cells. Once regulatory elements are defined, the cellular pathways that regulate expression in normal and neoplastic cells will be studied. Completion of these studies will provide a detailed picture of the transcriptional regulation of CDX genes in normal and neoplastic cells. This will provide the basis for understanding the network of cellular pathways that control these important cell specific transcription factors and how they are altered in neoplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: REGULATION OF UROKINASE RECEPTOR EXPRESSION IN COLON CA Principal Investigator & Institution: Boyd, Douglas D.; Professor; Tumor Biology; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2003; Project Start 01-JUL-1994; Project End 31-MAY-2008 Summary: (provided by applicant): The urokinase receptor (u-PAR) contributes to colon cancer invasion and metastasis partly by accelerating proteolysis, u-PAR transcription is >10 fold higher in invasive colon cancer and we are interested in identifying molecules upstream of transcription that regulate its expression. Since the protein tyrosine kinase Src activity is elevated > 8 fold in metastatic colon cancer and because transfection of Src into colonic epithelial cells renders them invasive, we hypothesize (Specific Aim # 1), that u-PAR expression is regulated by this protein tyrosine kinase. This will be tested by determining the effect of (a) a Src inhibitor (PP2) (b) a constitutively active or (c) dominant negative Src on u-PAR expression in cultured or genetically-induced (mucin 2 -/-) colon cancer and correlating u-PAR levels with Src activity in cultured and resected colon cancers. Our preliminary studies implicate a footprinted region (-148/-124) bound with Sp1/Sp3 that regulates constitutive and Src-inducible u-PAR expression. To determine the mechanism by which Src regulates u-PAR expression via this Sp1/Sp3 bound region (Specific Aim # 2), we will determine if Src (a) increases Sp1 expression (b) alters Sp1 phosphorylation to increase its DNA binding (c) increases histone acetylation at this footprinted region thereby promoting chromatin relaxation and Sp1/Sp3 binding or (d) increases the trans-acting activity of Sp1/Sp3. Our preliminary data indicate that
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Src regulates u-PAR expression in part through the Sp1/Sp3-bound -148/-124 region. In Specific Aim # 3, we will exploit this information in translational studies by determining the ability of a bisanthracycline WP631 (which blocks Sp1/Sp3 binding to the -148/-124 region) alone, or combined with a Src inhibitor (PP2), to suppress u-PAR expression and colon cancer invasiveness in vitro. Studies on u-PAR expression, to date, have employed in vitro techniques which provide no information on promoter requirements for tissue-specific u-PAR expression and ignore the role of chromatin in regulating this gene. In Specific Aim # 4, transgenic mice harboring a LacZ reporter regulated by 5' deleted u-PAR promoter fragments will be employed to determine (a) the minimal promoter sequence and (b) the role of the -148/-124 region required for u-PAR expression in the placenta and genetically-induced colon cancer (tissues characterized by their high u-PAR expression). Additionally, the sensitivity of transgene expression to Src inhibition will be determined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: ROLE OF FAS/FAS LIGAND IN PATHOGENESIS OF COLON CANCER Principal Investigator & Institution: Chen, Jian-Jun; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 11-SEP-2000; Project End 31-AUG-2005 Summary: (Applicant's Description): My current research interest is to learn more about molecular immunology and cancer pathogenesis. A better understanding of this process will allow us to develop novel anti-tumor therapies. My primary goal is to contribute to translational medicine. To this end, I have completed clinical training in internal medicine and gastroenterology. I also completed a research fellowship in the laboratory of Dr. Gary Nabel at University of Michigan. In July 1999, I began a new role as an assistant professor in the Department of Internal Medicine at the University of Michigan. I am setting up an independent laboratory that will extend the work I began during my fellowship. After completion of the award, I would like to pursue an academic career and participate in practice and research. The University of Michigan provides excellent laboratory facilities and active research environment. Dr. Gary Nabel who is an expert in cancer immunotherapy and gene therapy will continue to be my mentor. Furthermore, Dr. Chung Owyang who is expert in pathophysiology of digestive diseases will serve as my co-mentor. My current research is focused on the mechanisms by which tumors evade immune surveillance. We will investigate the role of Fas ligand and Fas in the pathogenesis of colon cancer. This will be accomplished first by examining whether FasL can suppress anti-tumor immunity in vivo. Then we will explore the mechanisms by which FasL+ tumors evade neutrophil attack. Finally, we will determine whether Fas-mediated apoptosis plays a role in preventing the development of colon cancer. The results obtained from this study should prove valuable to understand the pathogenesis of colon cancer and may lead to development of effective antitumor therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF PPARBETA IN COLON CARCINOGENESIS Principal Investigator & Institution: Peters, Jeffrey M.; Assistant Professor; Veterinary Science; Pennsylvania State University-Univ Park 201 Old Main University Park, PA 16802 Timing: Fiscal Year 2003; Project Start 06-MAY-2003; Project End 30-APR-2008
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Summary: (provided by applicant): Since it was first identified as a member of the peroxisome proliferator-activated receptors (PPARs) in 1994, specific roles for the PPARbeta (also referred to as PPAR-delta) have remained elusive, Recent data suggests that the PPAR-beta may be involved in epithelial cancer including skin and colon. PPARbeta expression is upregulated in response to topical application of a tumor promoter (TPA), in human colon tumor cells with an inactivated APC gene, and in human and azoxymethane-induced rodent colon tumors providing the first evidence suggesting that this receptor contributes to the mechanisms of epithelial cancers. Increased expression of beta-catenin caused by a mutant APC gene mediates transcriptional upregulation of PPAR-beta in colon tumor cells, demonstrating that PPAR-beta activation is downstream of the initial molecular events in the etiology of colon cancer. The central hypothesis of this proposal is that one functional role for PPAR-beta is to modulate target gene expression that leads to colon carcinogenesis. The first specific aim is to develop two model systems to test the hypotheses that PPAR-beta is essential for colon carcinogenesis. The first model will utilize crossing the PPAR-beta-null mouse line with APC min+/- mice and the second model will assess azoxymethane-induced colon cancer in the PPAR-beta null mouse. Results from these experiments will determine if increased PPAR-beta expression is central to the mechanisms underlying colon cancer. Western-style diets with a high fat content have been linked to higher incidence of colon cancer in both human and animal models and dietary fatty acids are known ligands for PPAR-beta. The second specific aim will test the hypothesis that increased colon cancer resulting from a high fat diet is dependent on PPAR-beta. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is used to prevent colon tumor formation, and may be due to inhibition of PPAR-beta-dependent target gene transcription and/or inhibition of COX metabolism. Preliminary data suggests that the beneficial effects of sulindac are mediated by the PPAR-beta. The third specific aim will determine if inhibition of colon carcinogenesis by the NSAID sulindac is mediated by PPARI-beta. Results from this work will also determine whether inhibition of PPAR-beta-dependent target gene transcription, inhibition of COX activity that may be influenced by PPAR-beta, or both, are critical to the mechanisms underlying sulindac inhibition of colon cancer. Combined, this work will clarify specific functional roles for the PPAR-beta in the molecular mechanisms underlying genetic, dietary and chemically induced colon cancer and in the prevention of this disease; thus providing future therapeutic targets to prevent colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: ROLE OF PROSTAGLANDIN H SYNTHASE 2 IN COLON CARCINOGENESIS Principal Investigator & Institution: Prescott, Stephen M.; H.A. & Edna Benning Presidential Profess; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2001 Summary: Studies of colon cancer using genetically engineered mice and chemicalcarcinogen treated animals, epidemiological studies of human populations, and clinical intervention trials (with non-steroidal anti-inflammatory drugs; NSAIDS) all indicate that cyclooxygenase (COX) lies on the most common pathway to colon cancer. The participation of COX appears to occur at an early stage in the pathway-just after the loss of the second allele of APC. There are two forms of COX; one is found under basal conditions in many cells and tissue, while the other, COX-2, is usually expressed only in response to growth factors, tumor promoters, and cytokines. We and others have shown that COX-2 is expressed in adenomatous polyps and colon carcinoma, and that this
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results at least in part from constitutive transcription. One aim of this project is to define the mechanisms for the abnormal transcription, and in another aim to explore the hypothesis that there is post-transcriptional regulation as well. In the third aim, we will test whether over-expression of COX-2 (or COX-1) in intestinal epithelium is sufficient to cause polyps and cancer, and if it is synergistic with a high fat diet or the presence of other mutations commonly found in colon cancer (APC, p53). The mechanism by which prostaglandin synthase promotes colon carcinogenesis is not known-prostaglandins might stimulate proliferation or inhibit apoptosis. Additionally, this enzyme(s) can catalyze the oxidation of xenobiotics, which might have analogous actions. Finally, the reactions catalyzed by COX can generate mutagens. We will examine each of these mechanisms using transgenic mice, cell lines, and human tissues, and technical approaches from cell biology, molecular biology, and biochemistry. The observations that well studied, inexpensive drugs (NSAIDS) can decrease the incidence of colon polyps and cancer offers an exciting opportunity for chemoprevention. This proposal seeks to elucidate the mechanisms by which this effect occurs and should open new approaches to prevention of colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: ROLE OF PROTEIN KINASE C IOTA IN COLON CARCINOGENESIS Principal Investigator & Institution: Murray, Nicole R.; Human Biol Chem and Genetics; University of Texas Medical Br Galveston 301 University Blvd Galveston, TX 77555 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Colon cancer results from progressive disregulation of the normal growth inhibitory, differentiation and apoptotic signals in colonic epithelial cells. Our long-term goal is to understand the role of protein kinase C (PKC) isozymes in colonic epithelial cell biology and colon carcinogenesis. Several lines of evidence suggest that the atypical PKC iota isoform (PKCi) plays an important promotive role in colon carcinogenesis. First, PKC expression is elevated in colon tumors relative to uninvolved colonic epithelium. Second, expression of PKCi protects cancer cells from apoptosis by activating NF-kB. Third, PKCi plays a requisite role in the transformation of intestinal epithelial cells by activated Ras, an oncogene commonly mutated in colon cancer. Fourth, inhibition of PKCi activity by dietary omega-3 fatty acids correlates with the cancer-preventive effects of omega-3 fatty acids. Taken together these data indicate that PKCi plays a key role in colon carcinogenesis by enhancing cell survival. We hypothesize that PKCi protects colonic epithelial cells against apoptosis and that elevated PKCi in the colonic epithelium will result in an increased susceptibility to colon carcinogenesis. We have generated transgenic mice that express constitutively active (ca) or dominant-negative (dn) mutant forms of PKCi in the colonic epithelium and have detected a decrease in basal apoptosis in the colonic epithelium of mice expressing caPKCi. In Specific Aim 1, we will determine the role of PKCi in colonic epithelial cell homeostasis by further characterizing our caPKCi and dnPKCi transgenic mice. Specific Aim 2 will assess the role of PKCi in mediating the effects of K-ras on colonic epithelial cell homeostasis and colon carcinogenesis in-vivo. Specific Aim 3 will determine the role of PKCi in Ras transformation and NF-kB signaling in intestinal epithelial cells in-vitro and in the colonic epithelium in-vivo. Specific Aim 4 will assess the role of PKCi in dietary fat-mediated changes in colonic epithelial cell homeostasis and colon carcinogenesis. These aims will be accomplished through the use of complementary transgenic mouse and rat intestinal epithelial cell models to assess the function of PKCi in the colonic epithelium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLES OF ERBB SIGNALING IN COLONIC CARCINOGENESIS Principal Investigator & Institution: Bissonnette, Marc M.; Research Associate (Associate Professor); Medicine; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2003; Project Start 29-JUL-1983; Project End 31-AUG-2008 Summary: (provided by applicant): ErbB receptors are tyrosine kinases that regulate colonocyte growth. Increases in EGFR (ErbB1), ErbB2 and several ErbB ligands in colon cancer suggest ErbB derangements contribute to colonic carcinogenesis. The azoxymethane (AOM) rat model of colon cancer recapitulates many features of human colon cancer, including alterations in ErbB signaling. In the prior grant cycle examining Ras activation, we identified AOM tumors with activated wild type Ras and increased expression of ErbB2, a Ras activator. In recent preliminary studies we showed EGFR, and several EGFR effectors were activated in AOM premalignancy. Moreover, Iressa, a specific EGFR antagonist, significantly inhibited (>80%) formation of aberrant crypt foci (ACF), putative precursors of colon cancer. We hypothesize that dys-regulated ErbB signals play important roles in colonic tumor initiation and growth. In the next cycle using the AOM model we will reveal potentially causal changes in ErbB signaling and examine the role of EGFR using genetic and pharmacological approaches. Caco-2 colon cancer cells express functional ErbB receptors and are widely studied for colonocyte growth and differentiation. Using Caco-2 stable transfectants we will elucidate changes in ligand-activated ErbB signaling induced by dominant negative (DN) ErbB or RNA interference (RNAi) strategies. Specific Aim 1 assess the contributions of ErbB signaling and the role of EGFR in AOM tumorigenesis: a) determine changes in ErbB receptors and ligands that occur in premalignancy and tumors; b) directly examine the role of EGFR in colonic carcinogenesis, using Iressa to block EGFR signaling in the rat; and employing mice homozygous for the Waved-2 (wa2) mutation in the EGFR catalytic domain that greatly attenuates kinase activity; and c) quantify carcinogen-induced activation of EGFR effectors, Src, PI3K and Ras and assess the effects of EGFR blockade on their activations. These studies will reveal potentially causal alterations induced by EGFR in these key EGFR effectors. Specific Aim 2 delineate the causal relationships between ErbB signaling and the biological consequences in Caco-2 cells using DN or RNAi strategies: a) Assess the effects of targeted inhibition of ErbB receptors on TGF-oc or heregulin-induced ErbB signaling and b) elucidate the biological phenotypes, including alterations in growth, apoptosis, tumorigenicity and invasiveness, induced by inhibition of specific ErbB receptors. With these studies, we will further elucidate the roles of ErbB signals in colonic carcinogenesis that can be exploited by selective targeting of receptors (e.g., EGFR blockade by Iressa) or effectors in future strategies to prevent or treat this malignancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SCREENING PRETEST FOR HEREDITARY COLON CANCER (HNPCC) Principal Investigator & Institution: Fields, Jeremy Z.; Principal Investigator; Ca*tx, Inc. 1110 Turner Blvd Omaha, NE 68105 Timing: Fiscal Year 2001; Project Start 01-MAR-2001; Project End 30-JUN-2003 Summary: Our goal is to develop a diagnostic assay to identify carriers of the hereditary colon cancer (HNPCC) trait using blood samples as the input specimen. In Phase 1 we will demonstrate the assay's feasibility, showing: 1) requisite predictive value, 2) practicality (easy, rapid, inexpensive), and 3) adaptability to automated technologies. Our assay should detect cellular changes in DNA mismatch repair (MMR) genes (MLH1
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& MSH2), changes that occur in HNPCC individuals due to mutation of one of the two alleles of the MLH1 or MSH2 gene. We already demonstrated plausibility for this strategy in preliminary models in which the assay outcome correlated with wild-type gene status. Our AIMS are: 1) to develop a predictive assay for MMR mutations that 1a) accurately demonstrates that the assay outcome correlates with genotype; 1b) distinguishes between cells homozygous and those heterozygous for the wild-type allele and between individuals with and without the HNPCC trait; 2) to adapt our assay to work with automated systems. This will lead to our Phase 2 objective: to integrate our assay into quantitative, commercial, automated systems. PROPOSED COMMERCIAL APPLICATION: The commercial application of our assay involves a practical test for hereditary nonpolyposis colon cancer (HNPCC) affecting over 5 million people in the western world. Detecting HNPCC before cancer develops offers a clinical benefit since cancer prevention strategies reduce their mortality. If technically feasible (Phase 1), the likelihood of our assay becoming commercialized (Phase 2) is outsanding because of the strong commitment of this project by Bayer Diagnostics, which nationally distributes automated diagnostic systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: SERUM IGFS--EFFECTS OF A SOY INTERVENTION IN HUMANS Principal Investigator & Institution: Lampe, Johanna W.; Associate Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, WA 98109 Timing: Fiscal Year 2001; Project Start 23-AUG-2001; Project End 31-JUL-2003 Summary: (provided by applicant): Insulin-like growth factors (IGFs) regulate cell proliferation in the body. IGF-I circulates in blood and acts to promote growth in tissues. Its carrier protein, IGFBP-3, binds IGF-I in circulation. This reduces IGF-I activity, but also increases its half-life in blood. In observational studies, high serum IGF-I, low serum IGFBP-3, or a high molar ratio of IGF-I relative to IGFBP-3 are associated with increased risk of breast, prostate, lung, and colon cancers, as well as larger colon polyps. This suggests that it may be beneficial to modify levels of circulating IGFs. Intervention studies in humans have shown that it is possible to alter levels of circulating IGFs; several classes of drugs and calorie or protein restriction all decrease serum IGF-I, increase IGFBP3, or both. Studies in animals and one report in humans suggest that isoflavones, bioactive agents in soybeans, can also alter IGF levels in directions that may protect against cancer. Our specific aim is to determine whether a 12-month soy isoflavone intervention alters serum IGF-I and IGFBP-3. Secondly, we seek to determine whether serum IGF concentrations are associated with colonic epithelial cell proliferation indices in individuals with adenomatous polyps. We propose to measure IGFs in serum that has been collected from 140 participants in the Soy Isoflavone Prevention Study (SIP; NC1 U0l CA7203501). SIP is a double-blinded, randomized, controlled trial in men and women, ages 50-80 years, with adenomatous polyps. SIP is a two-arm intervention. Participants consume a soy beverage that either contains isoflavones (intervention) or has had isoflavones removed (control). SIP is collecting and storing serum samples at 0,4, 8, and 12 months and colon biopsies at 0 and 12 months. We will measure serum IGF-I and IGFBP-3 in samples collected from the 4 time points, examine the effect of isoflavone intervention on IGF concentrations, and determine the relationship between IGFs and colon cell proliferation (Ki67-labeling). We will use data on cell proliferation and serum isoflavone concentrations from the SIP study. Thus, our proposed study makes efficient use of stored serum and other materials and data from the existing intervention. To date, SIP is the largest soy-isoflavone intervention in a study population at increased risk of colon cancer. It provides an ideal design to
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evaluate the effects of isoflavones on the IGF system and to explore relationships between IGFs and colonic epithelial cell proliferation in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: SPECTRAL AND NANO/MICROSCALE MARKERS OF COLON NEOPLASIA Principal Investigator & Institution: Backman, Vadim; Assistant Professor; Biomedical Engineering; Northwestern University 633 Clark St Evanston, IL 60208 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Colorectal cancer remains the second leading cause of cancer death in the United States. Since most of the American population fails to receive any kind of screening because of significant constraints from a health care delivery point of view, targeted colonoscopy to patients at elevated risk of colon cancer may be the most practical approach to pursue. Given that colorectal cancer represents a "field defect", identification of markers in the uninvolved colonic mucosa may represent an excellent method of risk-stratification. The ideal biomarker would be easily obtained from the patient with high sensitivity and positive predictive value. Numerous putative biomarkers have been proposed, but they have all lacked either sensitivity or have unacceptably high false positive rate thus making them suboptimal for clinical practice. Furthermore, these biomarkers are often insensitive to the molecular alterations in colon carcinogenesis. Recently, several lines of evidence suggest that micro-structural changes can be detected at very early time points and therefore may represent a promising intermediate biomarker. These abnormalities may occur at several levels including chromatin texture, nuclear size, ploidy, etc. However, detection of these abnormalities in situ requires novel techniques. We have recently pioneered light scattering spectroscopy (LSS) as a novel optical technology to probe the structure of living epithelial cells. This technique utilizes spectral analysis of the elastically scattered light to quantify tissue structure at scales ranging from the tens of nanometers (size of large macromolecular complexes) to several microns (size of cells and their nuclei). We hypothesize that distinct LSS signatures will be detectable in the premalignant mucosa and will be able to predict the development of colon cancers. These signatures will be used to establish how the cell organization and molecular events are interrelated and affect the development of cancer. Specifically, we will establish the spectroscopic signatures of macroscopicallynormal colon mucosa during various stages of carcinogenesis using the carcinogentreated rat model and evaluate LSS signatures in relation to time and dosage of carcinogen administration. The special emphasis will be on the characterization of the alterations of the nano/micro-architecture of living epithelial cell. Moreover, we will correlate these LSS signatures with occurrence of molecular and cellular changes important in the early stages of colon carcinogenesis. Furthermore, we will evaluate the ability of LSS to detect alterations in key signatures by an established non-steroidal antiinflammatory chemopreventive agent, sulindac. Our future directions would be to use this data to develop an instrument that could assess rectal mucosa LSS to identify patients at highest risk for colon cancer and target them for colonoscopy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SPECTROSCOPIC CHEMOPREVENTION
MARKERS
FOR
COLON
CANCER
Principal Investigator & Institution: Wali, Ramesh K.; Research Associate Professor; Evanston Northwestern Healthcare 2650 Ridge Ave Evanston, IL 60201
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Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Colorectal cancer (CRC) mortality remains a leading cause of cancer deaths in the United States underscoring the need for effective chemoprevention strategies. Number of agents have demonstrated chemopreventive efficacy in experimental models. However, clear clinical evidence has been lacking secondary to large number of patients that need long term monitoring for prevention endpoints. Intermediate biomarkers have been advocated, but most conventional markers are either insensitive or have suboptimal positive predictive value for colon carcinogenesis. Thus, discovering an easily detectable sensitive and accurate intermediate biomarker for colon carcinogenesis will be an incredible clinical tool in designing and testing new chemopreventive therapies. Ideally, such biomarker(s) would quantitatively assess the efficacy of a chemopreventive strategy early in the course of the therapy, which is of great benefit to patients, drug developers, and biomedical researchers. In this study, we propose to bridge the advances of optical spectroscopy and imaging to those of molecular biology in order to establish light scattering spectroscopy (LSS) in identifying micro/nanoscale ultrastructural signatures of the uninvolved colonic epithelium as accurate intermediate biomarker for chemoprevention of colon cancer. Our group has utilized LSS to accurately detect dysplastic changes in number of organs including colon and were the first to characterize the earliest precancerous transformations in colon cancer. LSS can be used to probe tissue structures ranging from few nanometers to several micrometer. Our preliminary data in experimental colon carcinogenesis strongly suggests that altered LSS signatures occur far earlier than the any classic genetic or cellular events. Moreover, using human colon cancer cell lines, we have shown that chemopreventive agents rapidly modulate LSS signatures far before detection of any other changes by conventional methods. We, therefore, hypothesize that LSS will provide sensitive and responsive intermediate biomarkers for chemoprevention of colon carcinogenesis. In this study, using AOMmodel of cancer, we will identify LSS signatures modulated by progression or prevention of cancer. One of the long term outcomes of this project would be to develop a novel technique to risk stratify patients for colon neoplasia, monitor chemopreventive strategies, and to non-invasively diagnose colon and potentially other cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: SPHINGOID BASE METABOLISM/ACTIVITIES IN VITRO & IN VITRO Principal Investigator & Institution: Merril, Alfred H.; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2001 Summary: The ceramide and sphingoid base backbones of sphingolipids are highly are highly bioactive compounds that affect growth, differentiation, cell migration and apoptosis when added to transformed cells in culture as well as when fed to mice treated when a colon carcinogen or that have a genetic that predisposes them to colon cancer. Based on the mechanisms of action of ceramides and sphingoid bases (and structure-function relationships for the metabolism of these compounds, synthetic analogs have been prepared that are more potent than the naturally compounds when tested against colon cancer cells in culture. This Program will characterize how these compounds are metabolized by cells in cultures and in vivo, as well as to evaluate the effectiveness of additional compounds that will be generated as part of a sphingolipid analog library. The specific aims will be to: 1) Analyze sphingolipid analogs as substrates/inhibitors of specific enzymatic targets in vitro. 2) Analyze cellular
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metabolism/effects of the sphingolipid analogs. 3) Analyze sphingolipid analog digestion, uptake and metabolism in vivo. An, 4) Analyze selected sphingolipid analogs for their effects on tumors in animals models for cancer. The findings of these studies will identify the most effective compounds and strategies for use of sphingolipids for the prevention and treatment of colon cancer and, perhaps, other forms of neoplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: SRC AS A NOVEL TARGET FOR HUMAN COLON CANCER THERAPY Principal Investigator & Institution: Yeatman, Timothy J.; Professor of Surgery, Biochemistry and m; Surgery; University of South Florida 4202 E Fowler Ave Tampa, FL 33620 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Applicant's Description) The goal of this grant proposal is to allow the principal investigator to mentor and train new physician scientists within the framework of pursuing translational research. The environment created will be invaluable to developing independent investigators who can truly bridge the gap between basic science and clinical application of novel therapeutics. Because the principal investigator (PI) was recently appointed as Program Leader for the Gastrointestinal Tumor Program at the H. Lee Moffitt Cancer Center, he has the authority to restructure the program with a central focus on colorectal cancer and Src oncogenesis. With this focus, basic laboratory research projects are now directly linked to new clinical trials. The PI's research has recently identified the novel finding of mutations in the Src proto-oncogene in advanced human colorectal cancer patients which are activating and transforming. This observation provides the rationale for pursuing Src-directed novel therapeutic agents such as tyrosine kinase inhibitors and angiogenesis inhibitors for the treatment of colorectal cancer. To support this effort, the PI has recently received a renewal of his funding through the American Cancer Society as a Research project Grant (MPG 97751; 1/99 - 1/02) entitled "Src Activation in Colon Cancer." We have several basic science collaborators who have provided us with a number of novel compounds which specifically inhibit Src or related tyrosine kinases in vitro and we are developing significant relationships with several pharmaceutical companies (Novartis, Zeneca, Sugen) which already have similar agents in the pipeline for clinical trials. The career plan presented in this application provides a direct relationship between the laboratory and the clinical application of novel therapeutics. The environment is ideal for the candidate interested in pursuing a career engaged in translational research. The surgical residency and the Society of Surgical Oncology approved surgical oncology fellowship will provide a continuous stream of candidates for this comprehensive laboratory and clinical research experience. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SRC KINASES IN COLON TUMORIGENESIS AND METASTASIS Principal Investigator & Institution: Gallick, Gary E.; Professor; Tumor Biology; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 01-MAY-1996; Project End 30-NOV-2003 Summary: Colorectal carcinoma currently ranks as the second most frequent form of cancer in the United States, with an estimated 150,000 cases discovered each year, and 56,000 deaths as a result of the disease. In the past several years, remarkably progress has been made toward identifying the genetic changes which lead to the development of
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the disease. However, this progress has yet to result in the development of new therapies that prolong the survival of patients with late stage colon cancer. A promising area of research that may also lead to the development of novel therapeutic agents is the study of signal transduction pathways in colon tumor cells. My laboratory and others have been studying the expression and activity of the non-receptor tyrosine kinases of the src family and their potential roles in the growth regulation of colonic epithelial cells. Src activation is one of the most frequent epigenetic events in colon cancer, and occurs early in the development of the disease. We have demonstrated that inhibition of Src activity alone decreases tumorigenicity of human colon carcinoma cells. To determine the role of Src activation in tumorigenicity, we have examined the regulation of Src- mediated pathways critical to growth control. We have shown that Src activation directly induces expression of vascular endothelial growth factor (VEGF), and further, through constitutive association with focal adhesion kinase (FAK), inhibits apoptosis. The studies proposed for the renewal of this grant are designed to better understand the molecular basis by which Src activation promotes these biological events. We will test the hypothesis that aberrant Src/FAK signaling complexes deregulate downstream intermediates of a common "Survival" pathway leading to VEGF expression and inhibition of apoptosis. While Src alone may be important to tumorigenic growth, both Src and Yes activation can occur in hepatic metastases, and with different prognostic results. Therefore, a second hypothesis to be tested in this proposal is that Src and Yes activation play distinct roles in tumor progression from those of tumorigenic growth. The specific aims of the proposal are to: (1) determine the requirement of interaction with focal adhesion kinase (FAK) for Src/Yes to exhibit their tumorigenic and/or metastatic potentials; (2) determine the role(s) of Src and FAK in mediating a common survival pathway leading to expression of vascular endothelial growth factor and inhibiting apoptosis; and (3) Determine the structural domains of Src required for its tumorigenic phenotype and if specific structural domains of Src and Yes induce differences in metastatic potential of establish colon tumor cell lines. Results from these studies will clarify important signal transduction pathways required for tumorigenic growth and metastasis of colon tumor cells, and intermediates in these pathways may serve as prognostic markers and/or targets for the disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: STATISTICAL INNOVATIONS IN RISK MODELING Principal Investigator & Institution: Rosner, Bernard A.; Professor; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2001 Summary: The overarching goal of this project is to further epidemiologic knowledge of breast, colon, and ovarian cancers, by exploring innovative risk modeling approaches. Another goal is to further the understanding of the study of combined outcomes, such as total mortality. There are three aims subsumed under these goals. Our first aim is to construct log- incidence models of colon cancer and ovarian cancer, analogous to the work that has been done with breast cancer. Compared to conventional logistic regression models, these non-linear allows more efficient testing of complex timedependent etiologic hypotheses They also permit the straightforward calculation of cumulative incidence, in addition to commonly-used relative risk measures. A second aim is to examine how well the above log-incidence models perform at clinical risk prediction at the individual level. Can these models accurately classify individual women with regard to disease status better than conventional logistic regression models, and can they perform well in an absolute sense? This issue of discriminatory
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accuracy is growing in importance; epidemiologic risk models are increasingly used by clinicians to provide patients with estimates of their personnel risk of disease, so that these individuals may make informed decisions may make informed decisions about prevention options. We will compare the discriminatory accuracy of the log- incidence models to the accuracy of conventional logistic regression models, and will compare results and conclusions obtained from ROC curve analyses to those obtained from traditional goodness-of-fit analyses which assess the difference between observed and expected values of (average) risk within specific subgroups of the sample population. It is likely that goodness-of-fit analyses are examination of combined endpoints, a common practice in epidemiology. The specific outcomes which comprise the combined outcome (e.g., mortality from different causes, in the combined outcome of total mortality) may evince different risk factor profiles. Statistical models which assume constancy of relative risk for a given risk factor are likely inappropriate when a combined outcome is being evaluated, though such models are often used. We will develop and expand the methodology of polychotomous logistic regression, which will permit the more accurate quantification of relative risk and benefits of exposures with respective to overall risk of adverse health outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: STUDIES OF A NOVEL CCK-B/GASTRIN RECEPTOR SPLICE VARIANT Principal Investigator & Institution: Hellmich, Mark R.; Surgery; University of Texas Medical Br Galveston 301 University Blvd Galveston, TX 77555 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (Applicant's Abstract): Colorectal cancer is the third leading cause of cancer death in the United States, Colon carcinogenesis is a complex, multi-step process involving progressive changes in signaling pathways regulating intestinal epithelial cell proliferation, differentiation and programmed death. The peptide hormone, gastrin 1-17 (G-17), and its non-amidated precursor, glycine-extended gastrin (G-GIy), exert potent trophic effects on colon cancer cells. The long-term goal is to understand the role of these peptide hormones in the regulation of epithelial cell biology and colon carcinogenesis. Although the growth-promoting effect of these peptides on colon cancers has been extensively documented, the identity of the receptors and intracellular signaling pathways involved remain controversial. The investigators have identified and isolated the cDNA for a novel splice variant of the human cholecystokininB/gastrin receptor (CCK-BR), a member of the G protein-coupled receptor (GPCR) superfamily. The splice variant (designated CCK-BRi4sv for intron 4 containing splice variant) encodes a receptor protein containing 69 additional amino acid residues in its putative third intracellular loop domain. CCK-BRi4sv is expressed in adenomatous polyps and colorectal cancers, but not in nonmalignant colonic mucosa adjacent to the cancer. Mouse Balb3T3 cells expressing the splice variant exhibited spontaneous, ligandindependent, oscillatory, increases in [Ca2+]i whereas, the same cells expressing wildtype CCK-BR (CCK-BRwt) did not. Similarly, primary cultures of human cells isolated from freshly resected colorectal cancers exhibited, ligand-independent, oscillatory increases in [Ca2+]. For both Balb3T3 and primary tumor cells, application of G-17 (10 and 200 nM, respectively) caused an increase in [Ca2+]i. Selective CCK-BR antagonists blocked the G- 17-stimulated Ca2+ responses, but not the spontaneous [Ca2+]i oscillations. In addition to spontaneous intracellular signaling, BaIb3T3 cells expressing CCK-BRi4sv exhibited an increased rate of cell proliferation (approximately 2.5-fold), in the absence of G-17, compared to cells expressing wild-type CCK-BR (CCK-BRwt).
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Based on these findings, the PI hypothesizes that CCK-BRi4sv may regulate colorectal cancer cell growth through both a gastrin-independent and -dependent mechanism and thus play a significant role in colorectal carcinogenesis. Furthermore, the PI hypothesizes that the function of CCK-BRi4sv in colorectal cancer biology is a direct consequence of the structural changes in the third intracellular loop domain, caused by intron retention, and the impact of those changes on intracellular signal transduction. To examine these hypotheses they plan experiments with the following specific aims: 1) to determine the spatial and temporal expression of the CCK-BR splice variant in adenomatous polyps and colon cancers; 2) to determine the effects of intron retention on receptor-mediated intracellular signal transduction and receptor desensitization/internalization; and 3) to determine the effects of ectopic expression of the CCK-BR splice variant on colonic epithelial cell homeostasis and susceptibility to carcinogen-induced colon cancer using a transgenic mouse model. These studies will provide important and new information regarding the role of the novel receptor splice variant and G-17 and G-Gly in epithelial cell biology and colon carcinogenesis. Furthermore, these studies may, in the future, provide the basis for the development of innovative therapeutic strategies for the treatment of peptide hormone-sensitive cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: TEA MODULATION OF COLON CARCINOGENESIS Principal Investigator & Institution: Wargovich, Michael J.; Professor; Pathology and Microbiology; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, SC 29208 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Green and black tea together represent the most commonly consumed beverages worldwide and is one of very few sources of phytochemicals with a broad chemopreventive activity against carcinogenesis. This activity and the lack of toxicity make tea an attractive agent for potential use in the reduction of human cancer risk. Consumption of green tea reduces risk for several cancers including lung, stomach, and pancreatic cancer. Recently it has been shown that habitual consumption of tea is associated with a reduced risk for colon cancer in a U.S. population. Nevertheless, much more research is needed before we can fully understand the cancer chemopreventive activities of tea and the possible application of tea in human cancer prevention. The overall goal of this project is to understand tea and cancer prevention by elucidating the mechanisms and identifying the active components involved. The Apc Min/+ mouse animal model for colon cancer and related cell lines will be used. This project will develop useful biomarkers, new agents (metabolites or analogs of the active components), and effective dosage forms for the prevention of human cancer. Specifically, we intend to test the hypothesis that orally administered tea is an effective inhibitor of carcinogenesis. The Min mouse and azoxymethane (AOM)treated Min mouse will be used as the animal models to conduct dose-response studies for the effect of tea on aberrant crypt foci and colon tumor formation. Possible differences between green tea and black tea and the effect of caffeine on colon tumorigenesis will be assessed. We next will determine the effect of green tea and black tea on the proliferation and apoptosis of cells in the colon and correlate it with the tumorigenesis results. To study the molecular mechanisms, tea will be tested for its ability to modulate AP-l, ERK, JNK, c-Jun, j3-catenin and other proteins in the colons of Min mice. To elucidate the mechanistic basis for the inhibition of colon turnorigenesis by green tea and black tea in the Min and AOMIMin mouse models studies on arachidonic acid metabolism, cyclooxygenase (COX) protein and mRNA levels, and activities of
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COX, lipoxygenase, and phospholipase A2 will be conducted with colon samples. Furthermore, studies examining the effect of tea polyphenols on the growth of human colon adenocarcinoma cells that have high levels of COX-2 expression will be conducted. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: TFF3 GENE EXPRESSION IN METASTATIC COLON CANCER Principal Investigator & Institution: Itzkowitz, Steven H.; The Dr. Burrill B. Crohn Professor of Me; Medicine; Mount Sinai School of Medicine of Nyu of New York University New York, NY 10029 Timing: Fiscal Year 2001; Project Start 15-JUL-1999; Project End 30-JUN-2002 Summary: Colorectal cancer is the second most common cause of cancer-related mortality in the United States, and 80 percent of patients who die of colorectal cancer have liver metastases. Since current treatments for metastatic colon cancer have achieved only limited success, there is an important need to develop novel and more effective treatment strategies. Our group has used suicide gene therapy based on the herpes simplex virus thymidine kinase gene plus ganciclovir to successfully treat colon cancer liver metastases in a syngeneic animal model. We have also demonstrated that placing the suicide gene under the control of the carcinoembryonic antigen (CEA) promoter affords greater tissue specificity. In addition, we have developed a binary gene expression construct in which the GAL4/VP16 transcription factors are placed under the control of the CEA promoter. This permitted the delivery of a higher dose of suicide gene-containing vector with better tumor cell killing and less toxicity. Although CEA is a useful prototype tumor-associated gene, its expression by many normal cells, particularly biliary epithelium, may result in unacceptable toxicity and limit its clinical utility. The identification of a gene that is more intestine-specific, while maintaining tumor-specificity, should offer the opportunity for greater therapeutic efficacy. Trefoil factor family 3 (TFF3; formerly called intestinal trefoil factor, ITF) is a promising candidate in this regard. TFF3 is primarily expressed by cells of the small and large intestine with no expression in the liver and very restricted expression in other normal organs. Evidence to date indicates that TFF3 expression is highly conserved during the progression from adenoma to carcinoma in the colon. TFF3 has been shown to phosphorylate b-catenin, thereby disrupting cell-cell adhesion and enabling cells to become motile which may explain the role of TFF3 in normal cell migration to heals mucosal wounds, but also for cancer cell invasion and metastasis. We have shown that all human colon cancer liver metastases studied express the TFF3 gene. Therefore, TFF3 appears to be an ideal candidate gene that has both tumor- and intestinal-specificity. The aims of this study are to: 1) Identify elements in the TFF3 promoter that confer colon-specific gene expression; 2) Create and test suicide gene constructs driven by the TFF3 promoter in vitro; and 3) Test the anti-tumor efficacy and toxicity of TFF3-suicide gene constructs in vivo. The use of the TFF3 gene to drive expression of suicide genes offers a novel approach which should result in more targetted, safer gene therapy for metastatic colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TGF BETA RECEPTOR AND TUMOR PROGRESSION Principal Investigator & Institution: Sun, Luzhe Z.; Associate Professor; Surgery; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, TX 78229 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2002
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Summary: (Applicant's Abstract) Transforming growth factor beta (TGF-beta) is one of a few polypeptide growth factors that negatively regulate the growth of various types of normal cells. Diminished or complete loss of autocrine TGF-beta activity is a hallmark in solid tumor progression. TGF-beta signal is transduced by a heteromeric complex of its type I (RI) and type II (RII) receptors present on cell surface. Studies showed that TGFbeta responsiveness is mainly due to down-regulation or mutation of one of the two receptors in various types of carcinomas. Studies have also showed that the expression of TGF-beta isoforms (termed beta 1, beta 2, and beta 3) is frequently up-regulated during tumor progression. Overexpression of TGF- beta 1 stimulated tumorigenicity of some TGF-beta-insensitive cancer cells suggesting that increased TGF-beta production with reduced receptor expression in cancer cells can render TGF-betas to act in a paracrine fashion on stroma to stimulate tumor growth. Currently, several mechanisms have been proposed to explain how paracrine TGF-beta might promote tumor progression. On the other hand, replacement of down- regulated or inactivated TGFbeta RI or RII restored autocrine TGF-beta growth inhibitory activity and suppressed tumorigenicity in a number of model systems including human breast and colon cancer cells, thus confirming that autocrine TGF-beta activity is tumor-suppressive in epithelial cancer cells. As such, it is conceivable that for the benefit of cancer therapy one should attempt to enhance autocrine TGF-beta activity while suppressing paracrine TGF-beta activity. In addition to RI and RII, TGF-betas also bind to another cell surface receptor called RIII that does not directly transduce TGF-beta signal. While RI/RII complex binds TGF-beta2 poorly, RIII has high affinity for all three isoforms. RIII has been shown to enhance TGF-beta binding to RI/RII complex suggesting that RIII may sequester TGFbeta to enhance its autocrine activity while abrogating its paracrine activity. Indeed, the applicant has recently reported that many human breast and colon cancer cells express reduced levels of RIII and re-expression of RIII enhanced autocrine TGF-beta activity and suppressed tumorigenicity in two breast cancer cell lines. Therefore, he hypothesizes that TGF-beta receptors, especially RIII, can be utilized to antagonize the paracrine tumor- promoting activity and enhance the autocrine tumor-suppressing activity of TGF-betas in breast and colon cancer cells so that their malignancy can be reverted. The applicant proposes to determine whether the extracellular domain of RIII and different TGF-beta receptor chimeras can be administered as drugs or delivered with gene therapy approaches to suppress tumorigenicity of cancer cells in mice. His goal is to determine whether these compounds are of potential use for cancer therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: TGF BETA RECEPTOR MUTATIONS AND HUMAN CANCER Principal Investigator & Institution: Grady, William M.; Assistant Professor of Medicine; Medicine; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2001; Project Start 01-MAY-1998; Project End 30-APR-2003 Summary: (Applicant's Description): Dr. William Grady completed an Internal Medicine residency at the University of Washington and is now completing a Gastroenterology fellowship at Case Western Reserve University. He has also commenced a research postdoctoral fellowship with Dr. Sanford Markowitz aimed at studying the role of TGFbeta receptor mutations in causing human g a strointestinal cancers. Dr. Markowitz's laboratory will provide a stimulating environment that will allow Dr. Grady to advance toward his long-term goal of becoming an independent investigator studying the molecular defects that give rise to human gastrointestinal cancers. The broad long-range objectives of this proposal are to define the role of TGF-beta receptor mutations in the genesis of gastrointestinal cancers. TGF-beta inhibits the growth of and induces
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apoptosis in human colonic epithelial cells. Previous studies in Dr. Markowitz's lab have demonstrated that TGF-beta receptor subunit type II (RII) mutations are found in 80%95% of colon and gastric cancers that have the replicative error phenotype (RER) and that TGF-beta RII acts as a tumor suppressor gene in RER colon cancer. The aims of this proposal are: 1) to determine the timing of RII mutations in the sequence of RER colon adenoma to colon carcinoma progression; 2) to determine the clinical subset of human gastric cancers which arise via RII mutations and the RER cancer pathway; 3) to determine the contributions of TGF-beta resistance, TGF-beta receptor type II (RII) and type I (RI) mutations, and defects in post-TGF-beta receptor signaling in the genesis of NonRER human colon cancers; 4) to use TGF-beta RII viral vectors to determine the antitumor activity of restored wild-type RII in suppressing colon cancer cell line growth, both in culture and in nude mice xenografts, and to determine the role of induction of apoptosis as part of the mechanism by which TGF-beta RII exerts its anti-tumor activity; and 5) to determine in the azoxymethane model of mouse colon carcinogenesis the promotion of colon adenoma and/or carcinoma formation resulting from introduction of a heterozygous RII gene knockout, and to confirm the role of RII inactivation in augmenting formation of these tumors by establishing the presence in them of mutational inactivation of the remaining wild-type RII allele. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: THE RON RECEPTOR IN THE INVASIVE GROWTH OF COLON CANCERS Principal Investigator & Institution: Wang, Ming-Hai; Associate Professor; Medicine; University of Colorado Hlth Sciences Ctr Uchsc at Fitzsimons Aurora, CO 800450508 Timing: Fiscal Year 2002; Project Start 05-JUN-2002; Project End 31-MAY-2006 Summary: (provided by applicant) Colon cancers are the second leading cause of cancer-related deaths in the United States. Although the genetic alternations associated with initiation and progression of colon cancers are well defined, the mechanisms by which tumors invade and metastasize require further investigation. Metastasis of colon cancers is the major cause of patient deaths. Thus, understanding the mechanisms of tumor metastasis is important and likely to be clinically useful. RON (Recepteur d'Origine Nantais) is a receptor tyrosine kinase belonging to the MET proto-oncogene family. Recent studies have shown that RON and its variants are highly expressed and constitutively activated in the majority of colon carcinoma cells, but not in normal colon mucosa or benign lesions. Moreover, RON activation induces a unique genetic program leading to cell dissociation, migration and matrix invasion. These data suggest that RON might be involved in the invasive growth and metastasis of colon cancers in vivo. The goal of this project is to study the cellular and molecular mechanisms by which RON mediates the invasive growth of colon carcinoma cells. The hypotheses underlying this proposal are: a) Cellular disorganization and genetic changes during the progression of colon cancers results in increased RON expression and its variant formation; b) RON has oncogenic/metastatic potential which is essential for the acquisition of motile-invasive phenotypes in colon cancers; and c) Acquisition of motile-invasive phenotypes by colon cancer cells is determined by the intracellular domains of RON that transduce a unique signaling pathway(s). To test these hypotheses, our studies will focus on: 1. Correlating RON and its variant expression in colon carcinoma cells with invasive behavior and clinical outcomes; 2. Determining the potential cellular mechanisms responsible for the abnormal RON expression and activation; 3. Studying how RON activation causes oncogenic and invasive activity in colon cancers cells; 4. Investigating the unique signaling pathway(s) of RON and its variants that elicit motile-invasive phenotypes in
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colon cancer cells. This work is important for several reasons. First, it will provide the basis for understanding the role of RON in the progression of colon cancers, particularly at the metastatic stages. Second, it will facilitate our understanding the mechanisms of how overexpression of a particular receptor tyrosine kinase results in the invasive growth and metastasis of colon cancers. Further, this work may lead to novel approaches for decreasing the metastasis of colon cancers in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: THERAPEUTIC TARGETING OF BETA-CATENIN IN COLON CANCER Principal Investigator & Institution: Drebin, Jeffrey A.; Surgery; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Genetic deletions of the adenomatous polyposis coil (APC) tumor suppressor gene occur in the majority of colon cancers Loss of the APC gene products' ability to down-regulate the beta-catenin protein is hypothesized to represent a critical mechanism by which APC loss contributes to the etiology of colon cancer However, the APC protein interacts with multiple other proteins, including gamma-catenin and hDLG, that may play a role in neoplastic cell growth To date there has been little direct examination of the role of beta-catenin in the neoplastic behavior of human colon cancer cells The precise mechanisms by which beta-catenin signaling enhances the growth and survival of neoplastic cells are unknown, and the characterization of changes in gene expression resulting from beta-catenin-mediated transcriptional effects has been limited The overall goal of this project is to directly evaluate the role of beta-catenin on the neoplastic properties of APC-mutant intestinal neoplasms Antisense oligodeoxynucleotides capable of specifically suppressing betacatenin expression in human cancer cells have been identified The ability of the antibiotic doxycycline, at clinically achievable concentrations, to inhibit beta-catenin expression has also been elucidated These beta-catenin-suppressive agents will be used to define beta-catenin-dependent effects on cell cycle and apoptotic regulatory mechanisms in APC-mutant colon cancer cells Effects of beta- catenin on c-myc expression and function will be characterized Changes in gene expression profiles of APC-mutant colon cancer cells resulting from suppression of beta-catenin expression will be evaluated, and compared with changes induced by upstream alterations in APC or downstream alterations in Tcf4 activity Effects of suppressing beta-catenin on spontaneous adenoma formation will be evaluated using APC-mutant min mice and antitumor effects resulting from the in vivo suppression of beta-catenin expression will be evaluated in APC-mutant human colon cancer xenografts Collectively, these studies will define the role of beta-catenin in the neoplastic growth of APC-mutant colon cancer cells and will characterize the efficacy of chemopreventive and therapeutic strategies that target beta-catenin in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSCRIPTIONAL CONTROL OF COLON CANCER THROUGH PPARY Principal Investigator & Institution: Spiegelman, Bruce M.; Professor; Dana-Farber Cancer Institute 44 Binney St Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 01-MAY-2000; Project End 30-APR-2005
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Summary: ( applicant's abstract) PPAR-gamma is a member of the nuclear receptor gene family that has been shown to play a key role in adipogenesis. PPAR-gamma is also expressed at very high levels in the colonic epithelium. Since colon cancer is a leading cause of cancer deaths, it is of great interest to understand the role of this receptor in the development of the colonic epithelium. The investigator's previous work has indicated that ligand activation of PPAR-gamma in human colon cancer cells induces a differentiative-like response including the cessation of cell growth and expression of genes characteristic of mature colonic epithelium. Most recently, he has shown that human colon cancer is associated with loss of function mutations in PPAR-gamma. Paradoxically, others have shown that TZD ligands, when applied to the polyp-prone min mouse that are genetically deficient in APC, develop more colon polyps. The present proposal will critically evaluate the role of PPAR-gamma in normal and abnormal colon development, and study the transcriptional mechanisms that underlie these functions. Firstly, the investigator will determine how PPAR-gamma intersects pathways known to regulate colon cell biology. Preliminary data show a strong connection between PPAR-gamma and TGF-beta signaling; hence, biochemical and genetic studies will focus on how Smad proteins interact with PPAR-gamma, and the relative contributions these interactions make to both signaling systems in the colon. The investigator will also study the transcriptional mechanisms that enable PPAR-gamma to induce a distinct program of gene expression when it is activated in colon cells. This will utilize both yeast 2-hybrid screens and biochemical purification to isolate components which interact with PPAR-gamma in a colon- or epithelium-selective manner. The function of novel proteins will be studied to discern their transcriptional and biological properties by expressing them in various mammalian cells. The program of colonselective genes regulated by PPAR-gamma will be better characterized through the use of SAGE analysis, applied to mRNA from colon cells treated with PPAR-gamma ligands. This work, done in collaboration with Dr. Ken Kinzler, will be used to characterize the expression of known genes, and to clone novel genes. Again, the function of downstream targets of PPAR-gamma will be characterized for their ability to regulate colon cell growth and differentiation. Finally, the role of PPAR-gamma in modulating colon cancer will be critically evaluated in transgenic mice, using potential dominant-negative alleles with a colon-selective promoter, and heterozygous PPARgamma KO mice that are already available. The initial studies will evaluate carcinogenesis using the chemical carcinogen DMH, though other transgenic methods of inducing colon cancer will also be evaluated. In summary, the investigator hopes that these studies will to provide a unique insight into the role of PPAR-gamma in normal and malignant colon development. Since PPAR-gamma ligands are clinically available now, this work may provide a framework in which to contemplate new therapeutic approaches to colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: TREATING CANCER OF THE GI USING CRYOMOLECULAR BIOLOGY Principal Investigator & Institution: Baust, John G.; Cryomedical Sciences, Inc. 1300 Piccard Dr, Ste L-105 Rockville, MD 20850 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JAN-2003 Summary: (provided by applicant): Cryomedical Sciences Inc. (CMSI) teamed with the University of Texas Medical Center and Johns Hopkins Medical Center proposes to develop cryosurgical procedures for the treatment of gastrointestinal (GI) cancers. This Phase 1 study will focus on molecular biological studies and development of prototype
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cryosurgical devices; whereas the Phase II work will focus on the application of these endoscopic cryosurgical devices in a canine model. CMSI recognizes a need to explore the molecular biological mechanisms of cell death that occur as a consequence of hypothermic(15 to 4C) and freezing (0C to -196C) episodes. CMSI is using molecular biological research to develop improved cryosurgical protocols through an understanding freeze-related cell death and survival. Data from cryosurgeons in the past few years have indicated that cancer cells in the middle of a tissue iceball created during cryosurgical procedures die immediately due to necrosis; whereas many of the cells that die in the iceball periphery where temperatures approach 0C die several days subsequent to cryoablation. While some of the peripheral cells survive the freezing insult. In vitro and molecular genetic studies performed at CMSI show that cells frozen at -70C die by necrosis; whereas at least 25 percent of the cells that die at -15C succumb via apoptosis. These observations lead to CMSI's in vitro cryochemo adjunct therapy studies showing that the addition of non-toxic levels of the apoptosis initiator 5fluorouracil (5-FU) to kidney, liver, prostate and most notably colon cancer cells enhances the efficacy of cryoablation. This Phase I grant will determine if (1) sub-lethal freezing of HT-29 and/or Caco-2 colon carcinoma cells results in the increase in synthesis of the cell death regulators, bcl-2, bax, Apaf 1, FADD, Fas and PARP; (2) sublethal freezing causes an up-regulation of caspase mRNA levels; (3) cell death due to freezing injury is cell cycle phase dependent and (4) modifications can be made to two prototype cryosurgical devices that are currently being designed for treating Barrett's esophagus and colon cancer to make them more useful and efficacious in the cryosurgical suite. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: UCP2 EXPRESSION IN COLON CANCER Principal Investigator & Institution: Baffy, Gyorgy; Rhode Island Hospital (Providence, Ri) Providence, RI 02903 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): SPECIFIC AIMS: 1) Determine the effects of dietary fatty acids on UCP2 expression. 2) Assess the influence of UCP2 during colon carcinogenesis in UCP2-/- mice. 3) Investigate the potential role of UCP2 in human colorectal cancer Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: USE OF LISTERIA AS COLON CANCER VACCINE ADJUVANTS Principal Investigator & Institution: Giedlin, Martin A.; Cerus Corporation 2411 Stanwell Dr Concord, CA 945204810 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 30-SEP-2003 Summary: (provided by the applicant): Colorectal cancer is the second leading cause of cancer death in the US. There is a 40 percent recurrence in patients treated surgically. Patients with distal metastatic disease have a low 5 yr survival rate with current chemotherapy. Therefore there is a critical need for improved options in the adjuvant setting. The principal goal of this SBIR Phase I proposal is to identify a panel of attenuated Listeria monocytogenes (Listeria) strains that can potentiate the immune response to cellular vaccines for colon cancer. Preliminary studies have suggested that Listeria administered following a therapeutic vaccination can target anti-tumor immune response specifically to liver metastases in a murine model of metastatic colon cancer, increasing the effectiveness of the vaccine by almost 5-fold. The various Listeria strains
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will be screened for relative pathogenicity and immunogenicity that characterize the innate and adaptive immune response. The immune response to these strains will also be assessed in the murine colorectal liver metastasis model. Appropriate attenuated strains of Listeria will be constructed to secrete GM-CSF and be evaluated for their ability to further augment the immune response to the vaccine in mice. Ultimately, this work will lead to novel adjuvant approaches to treating patients with advanced colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·
Project Title: VALIDATION OF HMGI-C AS A DRUG TARGET IN COLON CANCER Principal Investigator & Institution: Chouinard, Roland A.; Hmgene, Inc. 1308 Centennial Ave, #140 Piscataway, NJ 08854 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 29-FEB-2004 Summary: (provided by applicant): Colon cancer is a major health concern of the United States, with an estimated 129,400 new cases reported in 1999. Colon cancer is now the second leading cancer killer of both men and women in the U.S. after lung cancer. The successful management of this disease will require the discovery of safe and effective pharmacological agents. The goal of the present proposal is to validate HMGI-C (High Mobility Group I-C), an architectural transcription factor which regulates gene expression in tumorigenesis, as a drug target for colon cancer. The experimental approach will involve the inactivation of HMGI-C in Min mice, a widely accepted model of colon cancer resulting from an ethylnitrosurea (ENU) induced nonsense mutation at codon 850 of the murine Apc (adenomatous polyposis coli) gene. Germline mutations in humans in the APC gene are responsible for familial adenomatous polyposis, an inherited form of colon cancer. APC gene defects are also highly prevalent in sporadic colon tumors. It is hoped that inactivation of HMGI-C will attenuate colon cancer by inhibiting tumor formation or progression, thus validating HMGI-C as a drug target for colon cancer and setting the stage for a Phase II investigation into possible drug discovery. PROPOSED COMMERCIAL APPLICATION: Successful completion of this project would open up new prospects for the discovery of effective, clinically valuable drugs for the treatment of colon cancer which would have an enormous commercial potential. It is now estimated that in the United States alone, 129,400 new cases of colon cancer were reported, indicating the demand for safe, reliable pharmaceuticals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: WNT AND FRIZZLED SIGNALING IN MAMMARY ONCOGENESIS Principal Investigator & Institution: Kitajewski, Jan K.; Associate Professor; Obstetrics and Gynecology; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001; Project Start 06-JAN-1999; Project End 31-DEC-2003 Summary: (adapted from the investigator's abstract) The overall objective of the proposed work is to understand how the Wnt signal transduction pathway contributes to tumorigenesis. Their long term goal is to define how Wnt proteins and their downstream signaling components modulate cell growth. The general strategy will be to conduct biochemical and genetic analyses of the Wnt-signaling cascade in cultured mammary epithelial, colon, and other cell types. They will identify Wnt signaling components that induce cellular transformation and regulatory molecules that suppress Wnt-mediated transformation. Their focus is on disheveled, glycogen synthase kinase-3, beta-catenin, adenomatous polyposis coli (APC), axin (fused), TCF/Lef and on the
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potential interactions between Wnt and signaling cascades that include Akt and RhoA. Which of these signaling components are required for Wnt- mediated transformation will be evaluated by ectopically expressing their genes in cell lines that are sensitive to transformation by Wnt-1. The cell lines used in this study respond morphologically and mitogenically to Wnt-1 stimulation. Measurement of distinct biochemical activation steps will establish where in the signaling cascade novel components, like axin, function in Wnt signaling. The stability and signaling activity of cytosolic beta-catenin is tightly regulated by Wnt action. The applicant proposes to study the assembly and/or modification of beta-catenin complexes in the cytosol. These complexes will be analyzed in cells with Wnt signaling activated and compared to non-stimulated cells. The role of the newly discovered protein, axin, and the kinase Akt in Wnt signal transduction will be evaluated using both biological and biochemical assays. To define signal activation in human cancer we will use colon cancer cells with defined mutations in APC or betacatenin to analyze how the suppression of GSK-3 kinase uncouples beta-catenin from APC-mediated turnover and how axin acts to regulate beta-catenin stability and/or function. Mutations in APC and beta-catenin lead to activation of Wnt signaling in colon cancer, melanoma, and possibly several other human cancers. Thus, the Wnt signaling pathway is linked to the pathology of human cancers. It clearly represents an important problem in cancer biology with increasing relevance to human disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “colon cancer” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for colon cancer in the PubMed Central database: ·
A case of sigmoid endometriosis difficult to differentiate from colon cancer. by Dimoulios P, Koutroubakis IE, Tzardi M, Antoniou P, Matalliotakis IM, Kouroumalis EA. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=184504
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A systematic review of the effects of screening for colorectal cancer using the faecal occult blood test, Hemoccult. by Towler B, Irwig L, Glasziou P, Kewenter J, Weller D, Silagy C. 1998 Aug 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28648
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Cell Cycle Regulation of Metallothionein in Human Colonic Cancer Cells. by Nagel WW, Vallee BL. 1995 Jan 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42785
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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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Colorectal cancer screening: Recommendation statement from the Canadian Task Force on Preventive Health Care. by Care C. 2001 Jul 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=81309
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CpG island methylator phenotype in colorectal cancer. by Toyota M, Ahuja N, OheToyota M, Herman JG, Baylin SB, Issa JP. 1999 Jul 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17576
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Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. by Tsujii M, Kawano S, DuBois RN. 1997 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20370
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De novo Decorin Gene Expression Suppresses the Malignant Phenotype in Human Colon Cancer Cells. by Santra M, Skorski T, Calabretta B, Lattime EC, Iozzo RV. 1995 Jul 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41462
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Distinct Hypermethylation Patterns Occur at Altered Chromosome Loci in Human Lung and Colon Cancer. by Makos M, Nelkin BD, Lerman MI, Latif F, Zbar B, Baylin SB. 1992 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48567
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Effect of 2[prime prime or minute]-O-methyl antisense ORNs on expression of thymidylate synthase in human colon cancer RKO cells. by Schmitz JC, Yu D, Agrawal S, Chu E. 2001 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=29681
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Effects of peroxisome proliferator-activated receptor [delta] on placentation, adiposity, and colorectal cancer. by Barak Y, Liao D, He W, Ong ES, Nelson MC, Olefsky JM, Boland R, Evans RM. 2002 Jan 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117556
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Epidermal growth factor receptor activation induces nuclear targeting of cyclooxygenase-2, basolateral release of prostaglandins, and mitogenesis in polarizing colon cancer cells. by Coffey RJ, Hawkey CJ, Damstrup L, Graves-Deal R, Daniel VC, Dempsey PJ, Chinery R, Kirkland SC, DuBois RN, Jetton TL, Morrow JD. 1997 Jan 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19569
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ETS1 Suppresses Tumorigenicity of Human Colon Cancer Cells. by Suzuki H, Romano-Spica V, Papas TS, Bhat NK. 1995 May 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41960
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Expression profiling of blood samples from an SU5416 Phase III metastatic colorectal cancer clinical trial: a novel strategy for biomarker identification. by DePrimo SE, Wong LM, Khatry DB, Nicholas SL, Manning WC, Smolich BD, O'Farrell AM, Cherrington JM. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152639
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Fine Mapping of Colon Tumor Susceptibility (Scc) Genes in the Mouse, Different from the Genes Known to be Somatically Mutated in Colon Cancer. by Moen CJ, Groot PC, Hart AA, Snoek M, Demant P. 1996 Feb 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40034
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Frameshift-mutation-derived peptides as tumor-specific antigens in inherited and spontaneous colorectal cancer. by Saeterdal I, Bjorheim J, Lislerud K, Gjertsen MK, Bukholm IK, Olsen OC, Nesland JM, Eriksen JA, Moller M, Lindblom A, Gaudernack G. 2001 Nov 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60857
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Genetic disruption of PPAR[delta] decreases the tumorigenicity of human colon cancer cells. by Park BH, Vogelstein B, Kinzler KW. 2001 Feb 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30184
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Hereditary nonpolyposis colon cancer. by McLeod RS. 2001 Nov 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=81613
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Hereditary nonpolyposis colon cancer. by Lemire EG. 2001 Nov 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=81612
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High Expression of the DNA Methyltransferase Gene Characterizes Human Neoplastic Cells and Progression Stages of Colon Cancer. by El-Deiry WS, Nelkin BD, Celano P, Yen RC, Falco JP, Hamilton SR, Baylin SB. 1991 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51469
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HLTF gene silencing in human colon cancer. by Moinova HR, Chen WD, Shen L, Smiraglia D, Olechnowicz J, Ravi L, Kasturi L, Myeroff L, Plass C, Parsons R, Minna J, Willson JK, Green SB, Issa JP, Markowitz SD. 2002 Apr 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123687
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Human Colorectal Cancers Display Abnormal Fourier-Transform Infrared Spectra. by Rigas B, Morgello S, Goldman IS, Wong PT. 1990 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54908
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Huntingtin-interacting protein 1 is overexpressed in prostate and colon cancer and is critical for cellular survival. by Rao DS, Hyun TS, Kumar PD, Mizukami IF, Rubin MA, Lucas PC, Sanda MG, Ross TS. 2002 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151092
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Identifying and managing patients at low risk of bowel cancer in general practice. by Thompson MR, Heath I, Ellis BG, Swarbrick ET, Wood LF, Atkin WS. 2003 Aug 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=167156
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Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials. by Renehan AG, Egger M, Saunders MP, O'Dwyer ST. 2002 Apr 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100789
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Interactions of Human hMSH2 with hMSH3 and hMSH2 with hMSH6: Examination of Mutations Found in Hereditary Nonpolyposis Colorectal Cancer. by Guerrette S, Wilson T, Gradia S, Fishel R. 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=109246
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Intestinal floras of populations that have a high risk of colon cancer.. by Moore WE, Moore LH. 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=167598
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JC virus DNA is present in the mucosa of the human colon and in colorectal cancers. by Laghi L, Randolph AE, Chauhan DP, Marra G, Major EO, Neel JV, Boland CR. 1999 Jun 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22112
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Limited Up-Regulation of DNA Methyltransferase in Human Colon Cancer Reflecting Increased Cell Proliferation. by Lee PJ, Washer LL, Law DJ, Boland CR, Horon IL, Feinberg AP. 1996 Sep 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38390
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Liver Colonization Competence Governs Colon Cancer Metastasis. by Kuo T, Kubota T, Watanabe M, Furukawa T, Teramoto T, Ishibiki K, Kitajima M, Moosa AR, Penman S, Hoffman RM. 1995 Dec 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40301
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Mad-1 Is the Exclusive JC Virus Strain Present in the Human Colon, and Its Transcriptional Control Region Has a Deleted 98-Base-Pair Sequence in Colon Cancer Tissues. by Ricciardiello L, Chang DK, Laghi L, Goel A, Chang CL, Boland CR. 2001 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=115147
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Models of Human Metastatic Colon Cancer in Nude Mice Orthotopically Constructed by Using Histologically Intact Patient Specimens. by Fu X, Besterman JM, Monosov A, Hoffman RM. 1991 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52711
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Molecular karyotype (amplotype) of metastatic colorectal cancer by unbiased arbitrarily primed PCR DNA fingerprinting. by Malkhosyan S, Yasuda J, Soto JL, Sekiya T, Yokota J, Perucho M. 1998 Aug 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21480
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Mutation frequencies at codon 248 of the p53 tumour suppressor gene are not increased in colon cancer cell lines with the RER+ phenotype.. by Mancuso T, Aguilar F, Pescarolo MP, Clerico L, Russo P, Parodi S. 1997 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146940
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Nuclear Matrix Proteins in Human Colon Cancer. by Keesee SK, Meneghini MD, Szaro RP, Wu Y. 1994 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43274
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p21WAF1 is required for butyrate-mediated growth inhibition of human colon cancer cells. by Archer SY, Meng S, Shei A, Hodin RA. 1998 Jun 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22637
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p53 Mutations in Colorectal Cancer. by Rodrigues NR, Rowan A, Smith ME, Kerr IB, Bodmer WF, Gannon JV, Lane DP. 1990 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54786
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Patterns of Gene Expression that Characterize the Colonic Mucosa in Patients at Genetic Risk for Colonic Cancer. by Augenlicht LH, Taylor J, Anderson L, Lipkin M. 1991 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51431
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Population-based fecal occult blood screening for colon cancer: Will the benefits outweigh the harm? by Marshall KG. 2000 Sep 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=80462
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Potential role and chronology of abnormal expression of the Deleted in Colon Cancer (DCC) and the p53 proteins in the development of gastric cancer. by Graziano F, Cascinu S, Staccioli MP, Catalano V, Rossi MC, Baldelli AM, Giordani P, Muretto P, Catalano G. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=37544
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Prostacyclin-mediated activation of peroxisome proliferator-activated receptor [delta] in colorectal cancer. by Gupta RA, Tan J, Krause WF, Geraci MW, Willson TM, Dey SK, DuBois RN. 2000 Nov 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27215
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Prostaglandin H Synthase 2 is Expressed Abnormally in Human Colon Cancer: Evidence for a Transcriptional Effect. by Kutchera W, Jones DA, Matsunami N, Groden J, McIntyre TM, Zimmerman GA, White RL, Prescott SM. 1996 May 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39362
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Receptor protein tyrosine kinase EphB4 is up-regulated in colon cancer. by Stephenson SA, Slomka S, Douglas EL, Hewett PJ, Hardingham JE. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64642
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Synchronous Cardiac Myxoma and Colorectal Cancer A Case Report. by Nuno IN, Kang TY, Arroyo H, Starnes VA. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101182
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Time dependent ethnic convergence in colorectal cancer survival in hawaii. by Pagano IS, Morita SY, Dhakal S, Hundahl SA, Maskarinec G. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151602
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Up-regulation of plasma membrane-associated ganglioside sialidase (Neu3) in human colon cancer and its involvement in apoptosis suppression. by Kakugawa Y, Wada T, Yamaguchi K, Yamanami H, Ouchi K, Sato I, Miyagi T. 2002 Aug 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125023
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Variable [beta]-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. by Brabletz T, Jung A, Reu S, Porzner M, Hlubek F, Kunz-Schughart LA, Knuechel R, Kirchner T. 2001 Aug 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=56965
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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with colon cancer, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “colon cancer” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for colon cancer (hyperlinks lead to article summaries): ·
A caution regarding lymphatic mapping in patients with colon cancer. Author(s): Feig BW, Curley S, Lucci A, Hunt KK, Vauthey JN, Mansfield PF, Cleary K, Hamilton S, Ellis V, Brame M, Berger DH. Source: Am J Surg. 2001 December; 182(6): 707-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11839343&dopt=Abstract
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A cyclooxygenase-2 inhibitor (SC-58125) blocks growth of established human colon cancer xenografts. Author(s): Williams CS, Sheng H, Brockman JA, Armandla R, Shao J, Washington MK, Elkahloun AG, DuBois RN. Source: Neoplasia. 2001 September-October; 3(5): 428-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11687954&dopt=Abstract
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A germline E-cadherin mutation in a family with gastric and colon cancer. Author(s): Salahshor S, Hou H, Diep CB, Loukola A, Zhang H, Liu T, Chen J, Iselius L, Rubio C, Lothe RA, Aaltonen L, Sun XF, Lindmark G, Lindblom A. Source: Int J Mol Med. 2001 October; 8(4): 439-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11562785&dopt=Abstract
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A hemophagocytic syndrome-like condition after emergency colectomy for perforated colon cancer: report of a case. Author(s): Yamada T, Ikeya T, Ogawa T, Nakano M, Ogura H, Itoh H, Koyama T, Ohwada S, Yokoe T, Morishita Y. Source: Surg Today. 2002; 32(3): 278-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991518&dopt=Abstract
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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Studies 181
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A new TNM staging strategy for node-positive (stage III) colon cancer: an analysis of 50,042 patients. Author(s): Greene FL, Stewart AK, Norton HJ. Source: Ann Surg. 2002 October; 236(4): 416-21; Discussion 421. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368669&dopt=Abstract
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A novel lymphatic mapping technique to improve localization and staging of early colon cancer during laparoscopic colectomy. Author(s): Tsioulias GJ, Wood TF, Spirt M, Morton DL, Bilchik AJ. Source: Am Surg. 2002 July; 68(7): 561-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132733&dopt=Abstract
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A novel mechanism for aspirin-mediated growth inhibition of human colon cancer cells. Author(s): Goel A, Chang DK, Ricciardiello L, Gasche C, Boland CR. Source: Clin Cancer Res. 2003 January; 9(1): 383-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538492&dopt=Abstract
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A population-based study of the extent of surgical resection of potentially curable colon cancer. Author(s): Easson AM, Cotterchio M, Crosby JA, Sutherland H, Dale D, Aronson M, Holowaty E, Gallinger S. Source: Ann Surg Oncol. 2002 May; 9(4): 380-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986190&dopt=Abstract
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A rapid bioinformatic method identifies novel genes with direct clinical relevance to colon cancer. Author(s): Brett D, Kemmner W, Koch G, Roefzaad C, Gross S, Schlag PM. Source: Oncogene. 2001 July 27; 20(33): 4581-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11494154&dopt=Abstract
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A stochastic carcinogenesis model incorporating genomic instability fitted to colon cancer data. Author(s): Little MP, Wright EG. Source: Math Biosci. 2003 June; 183(2): 111-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711407&dopt=Abstract
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A targeted approach for antiangiogenic therapy of metastatic human colon cancer. Author(s): Ellis LM. Source: Am Surg. 2003 January; 69(1): 3-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12575772&dopt=Abstract
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A636P is associated with early-onset colon cancer in Ashkenazi Jews. Author(s): Guillem JG, Rapaport BS, Kirchhoff T, Kolachana P, Nafa K, Glogowski E, Finch R, Huang H, Foulkes WD, Markowitz A, Ellis NA, Offit K. Source: J Am Coll Surg. 2003 February; 196(2): 222-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595050&dopt=Abstract
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AACR special meeting in cancer research: colon cancer--genetics to prevention. Author(s): Johnstone CN, Chang LM, Ernst M; American Association for Cancer Research. Source: Cancer Res. 2002 November 15; 62(22): 6779-83. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438280&dopt=Abstract
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Aberrant expression and activation of the thrombin receptor protease-activated receptor-1 induces cell proliferation and motility in human colon cancer cells. Author(s): Darmoul D, Gratio V, Devaud H, Lehy T, Laburthe M. Source: Am J Pathol. 2003 May; 162(5): 1503-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707033&dopt=Abstract
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Activation of the PPAR pathway induces apoptosis and COX-2 inhibition in HT-29 human colon cancer cells. Author(s): Yang WL, Frucht H. Source: Carcinogenesis. 2001 September; 22(9): 1379-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11532858&dopt=Abstract
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Activity and expression of human telomerase in normal and malignant cells in gastric and colon cancer patients. Author(s): Nowak J, Januszkiewicz D, Lewandowski K, Nowicka-Kujawska K, Pernak M, Rembowska J, Nowak T, Wysocki J. Source: Eur J Gastroenterol Hepatol. 2003 January; 15(1): 75-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544698&dopt=Abstract
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Activity and properties of alpha-L-fucosidase are dependent on the state of enterocytic differentiation of HT-29 colon cancer cells. Author(s): Merino-Trigo A, Rodriguez-Berrocal FJ, de Miguel E, Paez de la Cadena M. Source: Int J Biochem Cell Biol. 2002 October; 34(10): 1291-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127580&dopt=Abstract
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Adenovirus-mediated gene transfer of P16INK4/CDKN2 into bax-negative colon cancer cells induces apoptosis and tumor regression in vivo. Author(s): Tamm I, Schumacher A, Karawajew L, Ruppert V, Arnold W, Nussler AK, Neuhaus P, Dorken B, Wolff G. Source: Cancer Gene Ther. 2002 August; 9(8): 641-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12136424&dopt=Abstract
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Adjuvant chemotherapy in stage III colon cancer with 5-fluorouracil and levamisole versus 5-fluorouracil and leucovorin. Author(s): Dencausse Y, Hartung G, Sturm J, Kopp-Schneider A, Hagmuller E, Wojatschek C, Lindemann H, Fritze D, Queisser W. Source: Onkologie. 2002 October; 25(5): 426-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415196&dopt=Abstract
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Adjuvant chemotherapy use for Medicare beneficiaries with stage II colon cancer. Author(s): Schrag D, Rifas-Shiman S, Saltz L, Bach PB, Begg CB. Source: J Clin Oncol. 2002 October 1; 20(19): 3999-4005. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12351597&dopt=Abstract
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Adjuvant therapy in colon cancer: current status and future directions. Author(s): Chau I, Cunningham D. Source: Cancer Treat Rev. 2002 October; 28(5): 223-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435370&dopt=Abstract
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Advanced proximal colon cancer. Author(s): Gannon CJ, Malone DL, Royal RE, Schreiber M, Bass BL, Napolitano LM. Source: Surg Endosc. 2002 March; 16(3): 446-9. Epub 2001 November 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11928025&dopt=Abstract
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Age-dependent variations of human and rat colon myofibroblasts in culture: Influence on their functional interactions with colon cancer cells. Author(s): Pourreyron C, Dumortier J, Ratineau C, Nejjari M, Beatrix O, Jacquier MF, Remy L, Chayvialle JA, Scoazec JY. Source: Int J Cancer. 2003 March 10; 104(1): 28-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12532416&dopt=Abstract
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Agreement between proxy- and case-reported information obtained using the selfadministered Ontario Familial Colon Cancer Registry epidemiologic questionnaire. Author(s): Nadalin V, Cotterchio M, McKeown-Eyssen G, Gallinger S. Source: Chronic Dis Can. 2003 Winter; 24(1): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757630&dopt=Abstract
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Alphavbeta3 integrin antagonist S247 decreases colon cancer metastasis and angiogenesis and improves survival in mice. Author(s): Reinmuth N, Liu W, Ahmad SA, Fan F, Stoeltzing O, Parikh AA, Bucana CD, Gallick GE, Nickols MA, Westlin WF, Ellis LM. Source: Cancer Res. 2003 May 1; 63(9): 2079-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727823&dopt=Abstract
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Alterations of anaphase-promoting complex genes in human colon cancer cells. Author(s): Wang Q, Moyret-Lalle C, Couzon F, Surbiguet-Clippe C, Saurin JC, Lorca T, Navarro C, Puisieux A. Source: Oncogene. 2003 March 13; 22(10): 1486-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629511&dopt=Abstract
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Altered expression of the mRNA stability factor HuR promotes cyclooxygenase-2 expression in colon cancer cells. Author(s): Dixon DA, Tolley ND, King PH, Nabors LB, McIntyre TM, Zimmerman GA, Prescott SM. Source: J Clin Invest. 2001 December; 108(11): 1657-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11733561&dopt=Abstract
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Alternative mRNA splicing in colon cancer causes loss of expression of neural cell adhesion molecule. Author(s): Huerta S, Srivatsan ES, Venkatesan N, Peters J, Moatamed F, Renner S, Livingston EH. Source: Surgery. 2001 November; 130(5): 834-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11685193&dopt=Abstract
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Amino acids interfere with the ERK1/2-dependent control of macroautophagy by controlling the activation of Raf-1 in human colon cancer HT-29 cells. Author(s): Pattingre S, Bauvy C, Codogno P. Source: J Biol Chem. 2003 May 9; 278(19): 16667-74. Epub 2003 February 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609989&dopt=Abstract
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Aminopeptidase N is involved in cell motility and angiogenesis: its clinical significance in human colon cancer. Author(s): Hashida H, Takabayashi A, Kanai M, Adachi M, Kondo K, Kohno N, Yamaoka Y, Miyake M. Source: Gastroenterology. 2002 February; 122(2): 376-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11832452&dopt=Abstract
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Aminosalicylates: potential antineoplastic actions in colon cancer prevention. Author(s): Allgayer H, Kruis W. Source: Scand J Gastroenterol. 2002 February; 37(2): 125-31. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11843045&dopt=Abstract
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Amplified Muc1-specific gene expression in colon cancer cells utilizing a binary system in adenoviral vectors. Author(s): Block A, Milasinovic D, Mueller J, Schaefer P, Schaefer H, Greten H. Source: Anticancer Res. 2002 November-December; 22(6A): 3285-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12530077&dopt=Abstract
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Angiogenesis inhibitor TNP-470 suppresses growth of peritoneal disseminating foci of human colon cancer line Lovo. Author(s): Fan YF, Huang ZH. Source: World J Gastroenterol. 2002 October; 8(5): 853-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378629&dopt=Abstract
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Angiopoietin-1 inhibits vascular permeability, angiogenesis, and growth of hepatic colon cancer tumors. Author(s): Stoeltzing O, Ahmad SA, Liu W, McCarty MF, Wey JS, Parikh AA, Fan F, Reinmuth N, Kawaguchi M, Bucana CD, Ellis LM. Source: Cancer Res. 2003 June 15; 63(12): 3370-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810673&dopt=Abstract
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Angiopoietins and their role in colon cancer angiogenesis. Author(s): Ellis LM, Ahmad S, Fan F, Liu W, Jung YD, Stoeltzing O, Reinmuth N, Parikh AA. Source: Oncology (Huntingt). 2002 April; 16(4 Suppl 3): 31-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014866&dopt=Abstract
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Anterograde colonoscopy: per oral diagnosis of colon cancer with an enteroscope in a man with a jejunoileal bypass. Author(s): Burton JR Jr, Katon R. Source: Gastrointest Endosc. 2003 June; 57(7): 982-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776063&dopt=Abstract
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Antisense telomerase induced cell growth inhibition, cell cycle arrest and telomerase activity down-regulation in gastric and colon cancer cells. Author(s): Wong SC, Yu H, Moochhala SM, So JB. Source: Anticancer Res. 2003 January-February; 23(1A): 465-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680250&dopt=Abstract
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Antitumor effects of 5-fluorouracil on human colon cancer cell lines: antagonism by levamisole. Author(s): Wiebke EA, Grieshop NA, Loehrer PJ, Eckert GJ, Sidner RA. Source: J Surg Res. 2003 May 1; 111(1): 63-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842449&dopt=Abstract
186 Colon Cancer
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Apoptosis induced by activation of peroxisome-proliferator activated receptor-gamma is associated with Bcl-2 and NF-kappaB in human colon cancer. Author(s): Chen GG, Lee JF, Wang SH, Chan UP, Ip PC, Lau WY. Source: Life Sci. 2002 April 19; 70(22): 2631-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12269390&dopt=Abstract
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Application of cDNA microarrays to generate a molecular taxonomy capable of distinguishing between colon cancer and normal colon. Author(s): Zou TT, Selaru FM, Xu Y, Shustova V, Yin J, Mori Y, Shibata D, Sato F, Wang S, Olaru A, Deacu E, Liu TC, Abraham JM, Meltzer SJ. Source: Oncogene. 2002 July 18; 21(31): 4855-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12101425&dopt=Abstract
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Application of laser capture microdissection and proteomics in colon cancer. Author(s): Lawrie LC, Curran S, McLeod HL, Fothergill JE, Murray GI. Source: Mol Pathol. 2001 August; 54(4): 253-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11477141&dopt=Abstract
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Are high-volume surgeons and hospitals the most important predictors of in-hospital outcome for colon cancer resection? Author(s): Ko CY, Chang JT, Chaudhry S, Kominski G. Source: Surgery. 2002 August; 132(2): 268-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12219022&dopt=Abstract
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Arsenic trioxide-induced apoptosis through oxidative stress in cells of colon cancer cell lines. Author(s): Nakagawa Y, Akao Y, Morikawa H, Hirata I, Katsu K, Naoe T, Ohishi N, Yagi K. Source: Life Sci. 2002 March 29; 70(19): 2253-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12005185&dopt=Abstract
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Associated changes of lipid peroxidation and transforming growth factor beta1 levels in human colon cancer during tumour progression. Author(s): Biasi F, Tessitore L, Zanetti D, Cutrin JC, Zingaro B, Chiarpotto E, Zarkovic N, Serviddio G, Poli G. Source: Gut. 2002 March; 50(3): 361-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11839715&dopt=Abstract
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Association between acetaminophen or nonsteroidal antiinflammatory drugs and risk of developing ovarian, breast, or colon cancer. Author(s): Meier CR, Schmitz S, Jick H. Source: Pharmacotherapy. 2002 March; 22(3): 303-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898889&dopt=Abstract
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Association between hemochromatosis (HFE) gene mutation carrier status and the risk of colon cancer. Author(s): Shaheen NJ, Silverman LM, Keku T, Lawrence LB, Rohlfs EM, Martin CF, Galanko J, Sandler RS. Source: J Natl Cancer Inst. 2003 January 15; 95(2): 154-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529348&dopt=Abstract
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Association of human polyomavirus JCV with colon cancer: evidence for interaction of viral T-antigen and beta-catenin. Author(s): Enam S, Del Valle L, Lara C, Gan DD, Ortiz-Hidalgo C, Palazzo JP, Khalili K. Source: Cancer Res. 2002 December 1; 62(23): 7093-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12460931&dopt=Abstract
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ATF3 gene regulates cell form and migration potential of HT29 colon cancer cells. Author(s): Ishiguro T, Nagawa H. Source: Oncol Res. 2000; 12(8): 343-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11589305&dopt=Abstract
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Attitudes towards genetic screening for predisposition to colon cancer among cancer patients, their relatives and members of the community. Results of focus group interviews. Author(s): Ramsey SD, Wilson S, Spencer A, Geidzinska A, Newcomb P. Source: Community Genet. 2003; 6(1): 29-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748436&dopt=Abstract
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Augmentation of sodium butyrate-induced apoptosis by phosphatidylinositol 3'kinase inhibition in the KM20 human colon cancer cell line. Author(s): Wang Q, Li N, Wang X, Kim MM, Evers BM. Source: Clin Cancer Res. 2002 June; 8(6): 1940-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12060639&dopt=Abstract
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Autophagy delays sulindac sulfide-induced apoptosis in the human intestinal colon cancer cell line HT-29. Author(s): Bauvy C, Gane P, Arico S, Codogno P, Ogier-Denis E. Source: Exp Cell Res. 2001 August 15; 268(2): 139-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11478840&dopt=Abstract
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Bacterial enterotoxins are associated with resistance to colon cancer. Author(s): Pitari GM, Zingman LV, Hodgson DM, Alekseev AE, Kazerounian S, Bienengraeber M, Hajnoczky G, Terzic A, Waldman SA. Source: Proc Natl Acad Sci U S A. 2003 March 4; 100(5): 2695-9. Epub 2003 February 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594332&dopt=Abstract
188 Colon Cancer
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Bacterial lipopolysaccharide induces transforming growth factor beta and hepatocyte growth factor through toll-like receptor 2 in cultured human colon cancer cells. Author(s): Yoshioka T, Morimoto Y, Iwagaki H, Itoh H, Saito S, Kobayashi N, Yagi T, Tanaka N. Source: J Int Med Res. 2001 September-October; 29(5): 409-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11725828&dopt=Abstract
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Bacteroides peritonitis associated with colon cancer in a continuous ambulatory peritoneal dialysis patient. Author(s): Nachimuthu S, Visconti EB, Pannone JB, Kaneb GC, Simonian H, Aung Z, Gopal L. Source: South Med J. 2001 October; 94(10): 1021-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11702814&dopt=Abstract
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Barrett's oesophagus, oesophageal cancer and colon cancer: an explanation of the association and cancer chemopreventive potential of non-steroidal anti-inflammatory drugs. Author(s): Morgan G, Vainio H. Source: Eur J Cancer Prev. 1998 June; 7(3): 195-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9696927&dopt=Abstract
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Base excision repair as a therapeutic target in colon cancer. Author(s): Liu L, Nakatsuru Y, Gerson SL. Source: Clin Cancer Res. 2002 September; 8(9): 2985-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12231545&dopt=Abstract
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Bax induction activates apoptotic cascade via mitochondrial cytochrome c release and Bax overexpression enhances apoptosis induced by chemotherapeutic agents in DLD1 colon cancer cells. Author(s): Kobayashi T, Sawa H, Morikawa J, Zhang W, Shiku H. Source: Jpn J Cancer Res. 2000 December; 91(12): 1264-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11123425&dopt=Abstract
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Bax plays a pivotal role in thapsigargin-induced apoptosis of human colon cancer HCT116 cells by controlling Smac/Diablo and Omi/HtrA2 release from mitochondria. Author(s): Yamaguchi H, Bhalla K, Wang HG. Source: Cancer Res. 2003 April 1; 63(7): 1483-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670894&dopt=Abstract
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B-cell leukemia protein-2 and peptide YY chemotherapy resistance in colon cancer. Author(s): Kling K, Kim F, Cole M, McFadden D. Source: Am J Surg. 1999 November; 178(5): 411-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10612539&dopt=Abstract
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Bcl-2 is a useful prognostic marker in Dukes' B colon cancer. Author(s): Meterissian SH, Kontogiannea M, Al-Sowaidi M, Linjawi A, Halwani F, Jamison B, Edwardes M. Source: Ann Surg Oncol. 2001 July; 8(6): 533-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11456053&dopt=Abstract
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Bcl-X(L) antisense sensitizes human colon cancer cell line to 5-fluorouracil. Author(s): Nita ME, Ono-Nita SK, Tsuno N, Tominaga O, Takenoue T, Sunami E, Kitayama J, Nakamura Y, Nagawa H. Source: Jpn J Cancer Res. 2000 August; 91(8): 825-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10965024&dopt=Abstract
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Beliefs associated with fecal occult blood test and colonoscopy use at a worksite colon cancer screening program. Author(s): Menon U, Champion VL, Larkin GN, Zollinger TW, Gerde PM, Vernon SW. Source: J Occup Environ Med. 2003 August; 45(8): 891-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915791&dopt=Abstract
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Benefits of combined radioimmunotherapy and anti-angiogenic therapy in a liver metastasis model of human colon cancer cells. Author(s): Li XF, Kinuya S, Yokoyama K, Koshida K, Mori H, Shiba K, Watanabe N, Shuke N, Michigishi T, Tonami N. Source: Eur J Nucl Med Mol Imaging. 2002 December; 29(12): 1669-74. Epub 2002 October 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458402&dopt=Abstract
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beta-Catenin regulates vascular endothelial growth factor expression in colon cancer. Author(s): Easwaran V, Lee SH, Inge L, Guo L, Goldbeck C, Garrett E, Wiesmann M, Garcia PD, Fuller JH, Chan V, Randazzo F, Gundel R, Warren RS, Escobedo J, Aukerman SL, Taylor RN, Fantl WJ. Source: Cancer Res. 2003 June 15; 63(12): 3145-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810642&dopt=Abstract
190 Colon Cancer
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Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Author(s): Jaiswal AS, Marlow BP, Gupta N, Narayan S. Source: Oncogene. 2002 December 5; 21(55): 8414-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466962&dopt=Abstract
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Beta-catenin-sensitive isoforms of lymphoid enhancer factor-1 are selectively expressed in colon cancer. Author(s): Hovanes K, Li TW, Munguia JE, Truong T, Milovanovic T, Lawrence Marsh J, Holcombe RF, Waterman ML. Source: Nat Genet. 2001 May; 28(1): 53-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11326276&dopt=Abstract
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Beta-galactoside alpha2,6 sialyltransferase in human colon cancer: contribution of multiple transcripts to regulation of enzyme activity and reactivity with Sambucus nigra agglutinin. Author(s): Dall'Olio F, Chiricolo M, Ceccarelli C, Minni F, Marrano D, Santini D. Source: Int J Cancer. 2000 October 1; 88(1): 58-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10962440&dopt=Abstract
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beta-lapachone induces cell cycle arrest and apoptosis in human colon cancer cells. Author(s): Huang L, Pardee AB. Source: Mol Med. 1999 November; 5(11): 711-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10656873&dopt=Abstract
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beta-Sitosterol inhibits growth of HT-29 human colon cancer cells by activating the sphingomyelin cycle. Author(s): Awad AB, von Holtz RL, Cone JP, Fink CS, Chen YC. Source: Anticancer Res. 1998 January-February; 18(1A): 471-3. Erratum In: Anticancer Res 1998 March-April; 18(2A): 1227. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9568122&dopt=Abstract
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Bilateral central retinal vein occlusion in a patient with occult colon cancer. Author(s): Segev F, Segev A, Livne A, Assia EI, Mekori YA. Source: Arch Ophthalmol. 2001 October; 119(10): 1552-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11594965&dopt=Abstract
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Bile acids mimic oxidative stress induced upregulation of thioredoxin reductase in colon cancer cell lines. Author(s): Lechner S, Muller-Ladner U, Schlottmann K, Jung B, McClelland M, Ruschoff J, Welsh J, Scholmerich J, Kullmann F. Source: Carcinogenesis. 2002 August; 23(8): 1281-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151345&dopt=Abstract
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Bile acids, fibre and colon cancer: the story unfolds. Author(s): Chaplin MF. Source: J R Soc Health. 1998 February; 118(1): 53-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9724940&dopt=Abstract
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Binding sites for Lewis antigens are expressed by human colon cancer cells and negatively affect their migration. Author(s): Hittelet A, Camby I, Nagy N, Legendre H, Bronckart Y, Decaestecker C, Kaltner H, Nifant'ev NE, Bovin NV, Pector JC, Salmon I, Gabius HJ, Kiss R, Yeaton P. Source: Lab Invest. 2003 June; 83(6): 777-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12808113&dopt=Abstract
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Biodistribution study of 188Re-labeled trisuccin-HuCC49 and trisuccinHuCC49deltaCh2 conjugates in athymic nude mice bearing intraperitoneal colon cancer xenografts. Author(s): Safavy A, Khazaeli MB, Safavy K, Mayo MS, Buchsbaum DJ. Source: Clin Cancer Res. 1999 October; 5(10 Suppl): 2994S-3000S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10541333&dopt=Abstract
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Bioinformatics-based discovery of a novel factor with apparent specificity to colon cancer. Author(s): De Young MP, Damania H, Scheurle D, Zylberberg C, Narayanan R. Source: In Vivo. 2002 July-August; 16(4): 239-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12224133&dopt=Abstract
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Biological properties and expression of mucins in 5-fluorouracil resistant HT29 human colon cancer cells. Author(s): Choi SR, Cho M, Kim HR, Ahn DH, Sleisenger MH, Kim YS. Source: Int J Oncol. 2000 July; 17(1): 141-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10853031&dopt=Abstract
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Biomarkers for early detection of colon cancer. Author(s): Srivastava S, Verma M, Henson DE. Source: Clin Cancer Res. 2001 May; 7(5): 1118-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11350874&dopt=Abstract
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Biosynthesis of the cancer-related sialyl-alpha 2,6-lactosaminyl epitope in colon cancer cell lines expressing beta-galactoside alpha 2,6-sialyltransferase under a constitutive promoter. Author(s): Dall'Olio F, Chiricolo M, Mariani E, Facchini A. Source: Eur J Biochem. 2001 November; 268(22): 5876-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11722575&dopt=Abstract
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Bispecific antibody targeting of doxorubicin to carcinoembryonic antigen-expressing colon cancer cell lines in vitro and in vivo. Author(s): Ford CH, Osborne PA, Rego BG, Mathew A. Source: Int J Cancer. 2001 June 15; 92(6): 851-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11351306&dopt=Abstract
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Blockade of insulin-like growth factor I receptor function inhibits growth and angiogenesis of colon cancer. Author(s): Reinmuth N, Liu W, Fan F, Jung YD, Ahmad SA, Stoeltzing O, Bucana CD, Radinsky R, Ellis LM. Source: Clin Cancer Res. 2002 October; 8(10): 3259-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374697&dopt=Abstract
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Blocking colon cancer. An aspirin a day helps. Author(s): Fischman J. Source: Us News World Rep. 2003 March 17; 134(8): 45. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645309&dopt=Abstract
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Body mass index and colon cancer in a national sample of adult US men and women. Author(s): Ford ES. Source: Am J Epidemiol. 1999 August 15; 150(4): 390-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10453815&dopt=Abstract
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Body mass index and colon cancer mortality in a large prospective study. Author(s): Murphy TK, Calle EE, Rodriguez C, Kahn HS, Thun MJ. Source: Am J Epidemiol. 2000 November 1; 152(9): 847-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11085396&dopt=Abstract
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Body mass index and colon cancer: an evaluation of the modifying effects of estrogen (United States). Author(s): Slattery ML, Ballard-Barbash R, Edwards S, Caan BJ, Potter JD. Source: Cancer Causes Control. 2003 February; 14(1): 75-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708728&dopt=Abstract
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Body size and the risk of colon cancer in a large case-control study. Author(s): Caan BJ, Coates AO, Slattery ML, Potter JD, Quesenberry CP Jr, Edwards SM. Source: Int J Obes Relat Metab Disord. 1998 February; 22(2): 178-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9504326&dopt=Abstract
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Bone mass and the risk of colon cancer among postmenopausal women: the Framingham study. Author(s): Zhang Y, Felson DT, Ellison RC, Kreger BE, Schatzkin A, Dorgan JF, Cupples LA, Levy D, Kiel DP. Source: Am J Epidemiol. 2001 January 1; 153(1): 31-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11159144&dopt=Abstract
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Bone metastases in a patient with colon cancer depicted by Tc-99m carcinoembryonic antigen scintigraphy. Author(s): Bongers V, Verhaar-Langereis MJ, Hobbelink MG, Zonnenberg BA, de Klerk JM. Source: Clin Nucl Med. 2000 October; 25(10): 817-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11043724&dopt=Abstract
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Breast metastasis of primary colon cancer. Author(s): Ozakyol AH, Saricam T, Isiksoy S. Source: Am J Gastroenterol. 2000 August; 95(8): 2149. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10950097&dopt=Abstract
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Butyrate regulates E-cadherin transcription, isoform expression and intracellular position in colon cancer cells. Author(s): Barshishat M, Polak-Charcon S, Schwartz B. Source: Br J Cancer. 2000 January; 82(1): 195-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10638989&dopt=Abstract
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Butyrate sensitizes human colon cancer cells to TRAIL-mediated apoptosis. Author(s): Hernandez A, Thomas R, Smith F, Sandberg J, Kim S, Chung DH, Evers BM. Source: Surgery. 2001 August; 130(2): 265-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11490359&dopt=Abstract
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Butyrate-induced G2/M block in Caco-2 colon cancer cells is associated with decreased p34cdc2 activity. Author(s): Harrison LE, Wang QM, Studzinski GP. Source: Proc Soc Exp Biol Med. 1999 November; 222(2): 150-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10564539&dopt=Abstract
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Butyric acid induces apoptosis by up-regulating Bax expression via stimulation of the c-Jun N-terminal kinase/activation protein-1 pathway in human colon cancer cells. Author(s): Mandal M, Olson DJ, Sharma T, Vadlamudi RK, Kumar R. Source: Gastroenterology. 2001 January; 120(1): 71-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11208715&dopt=Abstract
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By the way doctor. I'm puzzled about the difference between colon polyps and endometrial polyps. A polyp found during a colonoscopy is always removed. Is the same true for an endometrial polyp? Do endometrial polyps put you at risk for uterine cancer the same way colon polyps do for colon cancer? Author(s): Robb-Nicholson C. Source: Harv Womens Health Watch. 2002 May; 9(9): 8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12021027&dopt=Abstract
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By the way, doctor...I've had small amounts of blood in my bowel movements from time to time for years. My doctor has done a pretty thorough evaluation and has ruled out colon cancer or anything serious: what I have is plain old hemorrhoids. I've heard of an operation using rubber bands that can get rid of them. Should I go ahead and have this procedure done? Author(s): Lee TH. Source: Harv Health Lett. 2000 June; 25(8): 8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10810052&dopt=Abstract
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Calcium intake and risk of colon cancer in women and men. Author(s): Wu K, Willett WC, Fuchs CS, Colditz GA, Giovannucci EL. Source: J Natl Cancer Inst. 2002 March 20; 94(6): 437-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11904316&dopt=Abstract
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Cancer-related serological recognition of human colon cancer: identification of potential diagnostic and immunotherapeutic targets. Author(s): Scanlan MJ, Welt S, Gordon CM, Chen YT, Gure AO, Stockert E, Jungbluth AA, Ritter G, Jager D, Jager E, Knuth A, Old LJ. Source: Cancer Res. 2002 July 15; 62(14): 4041-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124339&dopt=Abstract
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Capillary sodium dodecyl sulfate-DALT electrophoresis with laser-induced fluorescence detection for size-based analysis of proteins in human colon cancer cells. Author(s): Hu S, Jiang J, Cook LM, Richards DP, Horlick L, Wong B, Dovichi NJ. Source: Electrophoresis. 2002 September; 23(18): 3136-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12298085&dopt=Abstract
Studies 195
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Case of liver metastasis from colon cancer successfully treated by regional chemotherapy with mitomycin C alone. Author(s): Watanabe O, Haga S, Kato H, Ooishi T, Kobayashi S, Okabe T, Yoshimatsu K, Yokomizo H, Kumazawa K, Murayama M, Kajiwara T. Source: J Gastroenterol Hepatol. 2002 February; 17(2): 227-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966960&dopt=Abstract
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Caspase-8 and apoptosis-inducing factor mediate a cytochrome c-independent pathway of apoptosis in human colon cancer cells induced by the dietary phytochemical chlorophyllin. Author(s): Diaz GD, Li Q, Dashwood RH. Source: Cancer Res. 2003 March 15; 63(6): 1254-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649185&dopt=Abstract
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Celecoxib induces apoptosis by inhibiting 3-phosphoinositide-dependent protein kinase-1 activity in the human colon cancer HT-29 cell line. Author(s): Arico S, Pattingre S, Bauvy C, Gane P, Barbat A, Codogno P, Ogier-Denis E. Source: J Biol Chem. 2002 August 2; 277(31): 27613-21. Epub 2002 May 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12000750&dopt=Abstract
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Cellular determinants of oxaliplatin sensitivity in colon cancer cell lines. Author(s): Arnould S, Hennebelle I, Canal P, Bugat R, Guichard S. Source: Eur J Cancer. 2003 January; 39(1): 112-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504667&dopt=Abstract
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Characterisation of integrin-linked kinase signalling in sporadic human colon cancer. Author(s): Marotta A, Parhar K, Owen D, Dedhar S, Salh B. Source: Br J Cancer. 2003 June 2; 88(11): 1755-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771992&dopt=Abstract
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Characterisation of tumour-associated antigens in colon cancer. Author(s): Line A, Slucka Z, Stengrevics A, Silina K, Li G, Rees RC. Source: Cancer Immunol Immunother. 2002 November; 51(10): 574-82. Epub 2002 September 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384809&dopt=Abstract
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Characteristics of the peroxisome proliferator activated receptor gamma (PPARgamma) ligand induced apoptosis in colon cancer cells. Author(s): Shimada T, Kojima K, Yoshiura K, Hiraishi H, Terano A. Source: Gut. 2002 May; 50(5): 658-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11950812&dopt=Abstract
196 Colon Cancer
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Characterization of sporadic colon cancer by patterns of genomic instability. Author(s): Goel A, Arnold CN, Niedzwiecki D, Chang DK, Ricciardiello L, Carethers JM, Dowell JM, Wasserman L, Compton C, Mayer RJ, Bertagnolli MM, Boland CR. Source: Cancer Res. 2003 April 1; 63(7): 1608-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670912&dopt=Abstract
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Chemoprevention of colon cancer by calcium, vitamin D and folate: molecular mechanisms. Author(s): Lamprecht SA, Lipkin M. Source: Nat Rev Cancer. 2003 August; 3(8): 601-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894248&dopt=Abstract
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Chemoprevention of colon cancer: current status and future prospects. Author(s): Gustin DM, Brenner DE. Source: Cancer Metastasis Rev. 2002; 21(3-4): 323-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12549770&dopt=Abstract
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Chemotherapy enhances TNF-related apoptosis-inducing ligand DISC assembly in HT29 human colon cancer cells. Author(s): Lacour S, Micheau O, Hammann A, Drouineaud V, Tschopp J, Solary E, Dimanche-Boitrel MT. Source: Oncogene. 2003 March 27; 22(12): 1807-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660816&dopt=Abstract
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Chemotherapy for colon cancer in a well-defined French population: is it under- or over-prescribed? Author(s): Faivre-Finn C, Bouvier AM, Mitry E, Rassiat E, Clinard F, Faivre J. Source: Aliment Pharmacol Ther. 2002 March; 16(3): 353-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11876687&dopt=Abstract
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Chemotherapy-induced O(6)-benzylguanine-resistant alkyltransferase mutations in mismatch-deficient colon cancer. Author(s): Liu L, Schwartz S, Davis BM, Gerson SL. Source: Cancer Res. 2002 June 1; 62(11): 3070-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12036916&dopt=Abstract
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Chromosomal autonomy of hMLH1 methylation in colon cancer. Author(s): Li H, Myeroff L, Kasturi L, Krumroy L, Schwartz S, Willson JK, Stanbridge E, Casey G, Markowitz S. Source: Oncogene. 2002 February 21; 21(9): 1443-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11857087&dopt=Abstract
Studies 197
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Circulating levels of interleukin-10 and interleukin-6 in gastric and colon cancer patients before and after surgery: relationship with radicality and outcome. Author(s): Galizia G, Lieto E, De Vita F, Romano C, Orditura M, Castellano P, Imperatore V, Infusino S, Catalano G, Pignatelli C. Source: J Interferon Cytokine Res. 2002 April; 22(4): 473-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034030&dopt=Abstract
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Classification tree analysis: a statistical tool to investigate risk factor interactions with an example for colon cancer (United States). Author(s): Camp NJ, Slattery ML. Source: Cancer Causes Control. 2002 November; 13(9): 813-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12462546&dopt=Abstract
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Clinical application of oligonucleotide probe array for full-length gene sequencing of TP53 in colon cancer. Author(s): Takahashi Y, Ishii Y, Nagata T, Ikarashi M, Ishikawa K, Asai S. Source: Oncology. 2003; 64(1): 54-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457032&dopt=Abstract
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Clinical significance of transmembrane 4 superfamily in colon cancer. Author(s): Hashida H, Takabayashi A, Tokuhara T, Hattori N, Taki T, Hasegawa H, Satoh S, Kobayashi N, Yamaoka Y, Miyake M. Source: Br J Cancer. 2003 July 7; 89(1): 158-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838318&dopt=Abstract
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Co-expression of CD44v3 and heparanase is correlated with metastasis of human colon cancer. Author(s): Kuniyasu H, Chihara Y, Kubozoe T, Takahashi T. Source: Int J Mol Med. 2002 September; 10(3): 333-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12165810&dopt=Abstract
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Colectomy for colon cancer via a 7-cm minilaparotomy. Author(s): Nakagoe T, Sawai T, Tsuji T, Jibiki M, Nanashima A, Yamaguchi H, Yasutake T, Ayabe H. Source: Surg Today. 2001; 31(12): 1113-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11827197&dopt=Abstract
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Colon cancer during pregnancy. Author(s): Cappell MS. Source: Gastroenterol Clin North Am. 2003 March; 32(1): 341-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635422&dopt=Abstract
198 Colon Cancer
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Colon cancer in France: evidence for improvement in management and survival. Author(s): Faivre-Finn C, Bouvier-Benhamiche AM, Phelip JM, Manfredi S, Dancourt V, Faivre J. Source: Gut. 2002 July; 51(1): 60-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12077093&dopt=Abstract
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Colon cancer in women. Author(s): Tinley ST. Source: Awhonn Lifelines. 2001 June-July; 5(3): 26-32. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11982260&dopt=Abstract
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Colon cancer prevention with NO-releasing NSAIDs. Author(s): Kaza CS, Kashfi K, Rigas B. Source: Prostaglandins Other Lipid Mediat. 2002 February; 67(2): 107-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11936617&dopt=Abstract
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Colon cancer screening guidelines stress initial test's importance. Author(s): Mitka M. Source: Jama. 2003 March 5; 289(9): 1089-90. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622558&dopt=Abstract
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Colon cancer screening in the ambulatory setting. Author(s): Walsh JM, Posner SF, Perez-Stable EJ. Source: Prev Med. 2002 September; 35(3): 209-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202062&dopt=Abstract
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Colon cancer survival is associated with increasing number of lymph nodes analyzed: a secondary survey of intergroup trial INT-0089. Author(s): Le Voyer TE, Sigurdson ER, Hanlon AL, Mayer RJ, Macdonald JS, Catalano PJ, Haller DG. Source: J Clin Oncol. 2003 August 1; 21(15): 2912-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885809&dopt=Abstract
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Colon cancer. Author(s): Scott S. Source: Gastroenterol Nurs. 2003 May-June; 26(3): 137-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811327&dopt=Abstract
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Colon cancer. Author(s): Frontin KM. Source: Ethn Dis. 2002 Winter; 12(1): S2-66-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11913651&dopt=Abstract
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Colon cancer: do we need a staging system? Author(s): Greene FL, Cera SM. Source: Adv Surg. 2003; 37: 171-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953632&dopt=Abstract
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Colon cancer: prevention, diagnosis, treatment. Author(s): McCormick D, Kibbe PJ, Morgan SW. Source: Gastroenterol Nurs. 2002 September-October; 25(5): 204-11; Quiz, 211-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394397&dopt=Abstract
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COLOR: a randomized clinical trial comparing laparoscopic and open resection for colon cancer. Author(s): Hazebroek EJ; Color Study Group. Source: Surg Endosc. 2002 June; 16(6): 949-53. Epub 2002 March 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163961&dopt=Abstract
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Combined modality therapy for rectal and colon cancer. Author(s): Chawla AK, Kachnic LA, Clark JW, Willett CG. Source: Semin Oncol. 2003 August; 30(4 Suppl 9): 101-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12908141&dopt=Abstract
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Commentary: can dietary fatty acids affect colon cancer risk? Author(s): Leitzmann MF, Giovannucci EL. Source: Int J Epidemiol. 2003 April; 32(2): 209-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714538&dopt=Abstract
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Commentary: Colon cancer, folate and genetic status. Author(s): Fallon UB. Source: Int J Epidemiol. 2003 February; 32(1): 67-70. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690012&dopt=Abstract
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Comments on E. Giovannucci, "Insulin, insulin-like growth factors and colon cancer: a review of the evidence". Author(s): Grant WB. Source: J Nutr. 2002 August; 132(8): 2324; Author Reply 2325. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163683&dopt=Abstract
200 Colon Cancer
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Computational dissection of tissue contamination for identification of colon cancerspecific expression profiles. Author(s): Tureci O, Ding J, Hilton H, Bian H, Ohkawa H, Braxenthaler M, Seitz G, Raddrizzani L, Friess H, Buchler M, Sahin U, Hammer J. Source: Faseb J. 2003 March; 17(3): 376-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631577&dopt=Abstract
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Computed tomography colonography and colon cancer screening. Author(s): Dachman AH, Glick S, Yoshida H. Source: Semin Roentgenol. 2003 January; 38(1): 54-64. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698591&dopt=Abstract
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Concurrent mutations of K-ras oncogene at codons 12 and 22 in colon cancer. Author(s): Miyakura Y, Sugano K, Fukayama N, Konishi F, Nagai H. Source: Jpn J Clin Oncol. 2002 June; 32(6): 219-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110640&dopt=Abstract
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Conjugated linoleic acid (CLA) inhibits growth of Caco-2 colon cancer cells: possible mediation by oleamide. Author(s): Kim EJ, Jun JG, Park HS, Kim SM, Ha YL, Park JH. Source: Anticancer Res. 2002 July-August; 22(4): 2193-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12174903&dopt=Abstract
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Connexin 43, but not connexin 32, is mutated at advanced stages of human sporadic colon cancer. Author(s): Dubina MV, Iatckii NA, Popov DE, Vasil'ev SV, Krutovskikh VA. Source: Oncogene. 2002 July 25; 21(32): 4992-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12118378&dopt=Abstract
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Constipation, anthranoid laxatives, melanosis coli, and colon cancer: a risk assessment using aberrant crypt foci. Author(s): Nascimbeni R, Donato F, Ghirardi M, Mariani P, Villanacci V, Salerni B. Source: Cancer Epidemiol Biomarkers Prev. 2002 August; 11(8): 753-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163329&dopt=Abstract
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Constipation, laxative use, and colon cancer in a North Carolina population. Author(s): Roberts MC, Millikan RC, Galanko JA, Martin C, Sandler RS. Source: Am J Gastroenterol. 2003 April; 98(4): 857-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738468&dopt=Abstract
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Correspondence re: Samowitz et al., Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level. Cancer Epidemiol. Biomark. Prev., 10: 917-923, 2001. Author(s): Dolcetti R, Guidoboni M, Viel A, Boiocchi M. Source: Cancer Epidemiol Biomarkers Prev. 2002 May; 11(5): 499; Author Reply 499-500. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12010867&dopt=Abstract
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Counterpoint: From animal models to prevention of colon cancer. Criteria for proceeding from preclinical studies and choice of models for prevention studies. Author(s): Bruce WR. Source: Cancer Epidemiol Biomarkers Prev. 2003 May; 12(5): 401-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750233&dopt=Abstract
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COX selectivity and animal models for colon cancer. Author(s): Oshima M, Taketo MM. Source: Curr Pharm Des. 2002; 8(12): 1021-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11945149&dopt=Abstract
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COX-2: a target for colon cancer prevention. Author(s): Marnett LJ, DuBois RN. Source: Annu Rev Pharmacol Toxicol. 2002; 42: 55-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11807164&dopt=Abstract
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COX-2-independent antiproliferative action of acetylsalicylic acid in human colon cancer cells. Author(s): Goke MN. Source: Eur J Clin Invest. 2002 November; 32(11): 793-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12423318&dopt=Abstract
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Cryosurgical ablation of liver tumors in colon cancer patients increases the serum total ganglioside level and then selectively augments antiganglioside IgM. Author(s): Ravindranath MH, Wood TF, Soh D, Gonzales A, Muthugounder S, Perez C, Morton DL, Bilchik AJ. Source: Cryobiology. 2002 August; 45(1): 10-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445546&dopt=Abstract
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Cyclooxygenase-2 activity altered the cell-surface carbohydrate antigens on colon cancer cells and enhanced liver metastasis. Author(s): Kakiuchi Y, Tsuji S, Tsujii M, Murata H, Kawai N, Yasumaru M, Kimura A, Komori M, Irie T, Miyoshi E, Sasaki Y, Hayashi N, Kawano S, Hori M. Source: Cancer Res. 2002 March 1; 62(5): 1567-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11888937&dopt=Abstract
202 Colon Cancer
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Cyclooxygenase-2 overexpression inhibits death receptor 5 expression and confers resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human colon cancer cells. Author(s): Tang X, Sun YJ, Half E, Kuo MT, Sinicrope F. Source: Cancer Res. 2002 September 1; 62(17): 4903-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208739&dopt=Abstract
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Cyclooxygenase-2 overexpression reduces apoptotic susceptibility by inhibiting the cytochrome c-dependent apoptotic pathway in human colon cancer cells. Author(s): Sun Y, Tang XM, Half E, Kuo MT, Sinicrope FA. Source: Cancer Res. 2002 November 1; 62(21): 6323-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414664&dopt=Abstract
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Cyclooxygenases and colon cancer. Author(s): Kawai N, Tsujii M, Tsuji S. Source: Prostaglandins Other Lipid Mediat. 2002 August; 68-69: 187-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432918&dopt=Abstract
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Dairy foods and prevention of colon cancer: human studies. Author(s): Holt PR. Source: J Am Coll Nutr. 1999 October; 18(5 Suppl): 379S-391S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10511318&dopt=Abstract
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Dealing with colon cancer: one woman's emotional journey. Author(s): Wilson CT, Fletcher PC. Source: Clin Nurse Spec. 2002 November; 16(6): 298-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464845&dopt=Abstract
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Decisional consideration of hereditary colon cancer genetic test results among Hong Kong chinese adults. Author(s): Ho SM, Ho JW, Chan CL, Kwan K, Tsui YK. Source: Cancer Epidemiol Biomarkers Prev. 2003 May; 12(5): 426-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750237&dopt=Abstract
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Decoding the cryptic origins of colon cancer. Author(s): Twombly R. Source: Environ Health Perspect. 2002 July; 110(7): A394-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117656&dopt=Abstract
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Decreased production of insulin-like growth factor-binding protein (IGFBP)-6 by transfection of colon cancer cells with an antisense IGFBP-6 cDNA construct leads to stimulation of cell proliferation. Author(s): Kim EJ, Schaffer BS, Kang YH, Macdonald RG, Park JH. Source: J Gastroenterol Hepatol. 2002 May; 17(5): 563-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084030&dopt=Abstract
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Decreased synthesis of matrix metalloproteinase-7 and adhesion to the extracellular matrix proteins of human colon cancer cells treated with troglitazone. Author(s): Sunami E, Tsuno NH, Kitayama J, Saito S, Osada T, Yamaguchi H, Tomozawa S, Tsuruo T, Shibata Y, Nagawa H. Source: Surg Today. 2002; 32(4): 343-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027200&dopt=Abstract
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Deficient DNA mismatch repair: a common etiologic factor for colon cancer. Author(s): Peltomaki P. Source: Hum Mol Genet. 2001 April; 10(7): 735-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11257106&dopt=Abstract
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Defining optimal treatment for stage II colon cancer: does decision analysis help? Author(s): Schrag D. Source: Gastroenterology. 1999 October; 117(4): 1005-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10500083&dopt=Abstract
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Deguelin inhibits the growth of colon cancer cells through the induction of apoptosis and cell cycle arrest. Author(s): Murillo G, Salti GI, Kosmeder JW 2nd, Pezzuto JM, Mehta RG. Source: Eur J Cancer. 2002 December; 38(18): 2446-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12460790&dopt=Abstract
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Dendritic cell infiltration in colon cancer. Author(s): Schwaab T, Weiss JE, Schned AR, Barth RJ Jr. Source: J Immunother. 2001 March-April; 24(2): 130-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11265770&dopt=Abstract
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Deoxycholic acid stimulates migration in colon cancer cells. Author(s): Milovic V, Teller IC, Murphy GM, Caspary WF, Stein J. Source: Eur J Gastroenterol Hepatol. 2001 August; 13(8): 945-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11507360&dopt=Abstract
204 Colon Cancer
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Depressed type minute subserosal invasive colon cancer: report of a case. Author(s): Ueta H, Tamura S, Ohkawauchi K, Tadokoro T, Yokoyama Y, Matsuura Y, Morita M, Onishi S. Source: Gastrointest Endosc. 2000 December; 52(6): 778-80. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11115918&dopt=Abstract
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Depressed type submucosal invading colon cancer with type V pit pattern. Author(s): Tamura S, Yokoyama Y, Tadokoro T, Higashidani Y, Kohsaki T, Onishi S. Source: Gastrointest Endosc. 2001 March; 53(3): 340-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11231396&dopt=Abstract
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Depressed-type submucosal colon cancer: report of a case. Author(s): Kim HS, Park WK, Lee JD, Kim KY. Source: Dis Colon Rectum. 2002 May; 45(5): 693-6; Discussion 696-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12004223&dopt=Abstract
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Deregulated expression of homeobox-containing genes, HOXB6, B8, C8, C9, and Cdx1, in human colon cancer cell lines. Author(s): Vider BZ, Zimber A, Chastre E, Gespach C, Halperin M, Mashiah P, Yaniv A, Gazit A. Source: Biochem Biophys Res Commun. 2000 June 7; 272(2): 513-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10833444&dopt=Abstract
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Detection of aberrantly methylated hMLH1 promoter DNA in the serum of patients with microsatellite unstable colon cancer. Author(s): Grady WM, Rajput A, Lutterbaugh JD, Markowitz SD. Source: Cancer Res. 2001 February 1; 61(3): 900-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11221878&dopt=Abstract
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Detection of epithelial tumour RNA in the plasma of colon cancer patients is associated with advanced stages and circulating tumour cells. Author(s): Silva JM, Rodriguez R, Garcia JM, Munoz C, Silva J, Dominguez G, Provencio M, Espana P, Bonilla F. Source: Gut. 2002 April; 50(4): 530-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889075&dopt=Abstract
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Detection of peritoneal micrometastases by reverse transcriptase-polymerase chain reaction targeting carcinoembryonic antigen and cytokeratin 20 in colon cancer patients. Author(s): Aoki S, Takagi Y, Hayakawa M, Yamaguchi K, Futamura M, Kunieda K, Saji S. Source: J Exp Clin Cancer Res. 2002 December; 21(4): 555-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12636102&dopt=Abstract
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Determinants of activity of the antifolate thymidylate synthase inhibitors Tomudex (ZD1694) and GW1843U89 against mono- and multilayered colon cancer cell lines under folate-restricted conditions. Author(s): Peters GJ, Smitskamp-Wilms E, Smid K, Pinedo HM, Jansen G. Source: Cancer Res. 1999 November 1; 59(21): 5529-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10554030&dopt=Abstract
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Determination of histamine in the whole blood of colon cancer patients. Author(s): Previati M, Raspadori A, Bertolaso L, Parmeggiani A, Bindini D, Vitali C, Lanzoni I, Corbacella E, Saviano M, Fagioli F, Blo G, Capitani S. Source: J Chromatogr B Analyt Technol Biomed Life Sci. 2002 November 25; 780(2): 3319. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401359&dopt=Abstract
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Development of intracytoplasmic lumens in a colon cancer cell line cultured on a non-adhesive surface. Author(s): Bae SI, Kang GH, Kim YI, Lee BL, Kleinman HK, Kim WH. Source: Cancer Biochem Biophys. 1999 July; 17(1-2): 35-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10738900&dopt=Abstract
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DHPLC mutation analysis of the hereditary nonpolyposis colon cancer (HNPCC) genes hMLH1 and hMSH2. Author(s): Holinski-Feder E, Muller-Koch Y, Friedl W, Moeslein G, Keller G, Plaschke J, Ballhausen W, Gross M, Baldwin-Jedele K, Jungck M, Mangold E, Vogelsang H, Schackert HK, Lohsea P, Murken J, Meitinger T. Source: J Biochem Biophys Methods. 2001 January 30; 47(1-2): 21-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11179758&dopt=Abstract
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Diagnosis and management of hereditary colon cancer. Author(s): Cruz-Correa M, Giardiello FM. Source: Gastroenterol Clin North Am. 2002 June; 31(2): 537-49, X. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12134617&dopt=Abstract
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Diagnostic dilemmas in oncology. Case 3. Metastatic ovarian cancer simulating colon cancer. Author(s): Krop IE, Wieczorek TJ, Mayer RJ. Source: J Clin Oncol. 2000 September; 18(17): 3189-92. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10963649&dopt=Abstract
206 Colon Cancer
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Diagnostic potential of Fourier-transform infrared microspectroscopy and advanced computational methods in colon cancer patients. Author(s): Argov S, Ramesh J, Salman A, Sinelnikov I, Goldstein J, Guterman H, Mordechai S. Source: J Biomed Opt. 2002 April; 7(2): 248-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966311&dopt=Abstract
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Diagnostic use of the sentinel node in colon cancer. Author(s): Merrie AE, van Rij AM, Phillips LV, Rossaak JI, Yun K, Mccall JL. Source: Dis Colon Rectum. 2001 March; 44(3): 410-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11289289&dopt=Abstract
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Diarrhea or colorectal cancer: can bacterial toxins serve as a treatment for colon cancer? Author(s): Carrithers SL. Source: Proc Natl Acad Sci U S A. 2003 March 18; 100(6): 3018-20. Epub 2003 Mar 11. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631696&dopt=Abstract
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Diet, fibers, and colon cancer. Author(s): Faivre J, Bonithon-Kopp C. Source: Adv Exp Med Biol. 1999; 472: 199-206. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10736627&dopt=Abstract
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Diet, lifestyle, and colon cancer. Author(s): Slattery ML. Source: Semin Gastrointest Dis. 2000 July; 11(3): 142-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10950460&dopt=Abstract
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Dietary calcium and growth modulation of human colon cancer cells: role of the extracellular calcium-sensing receptor. Author(s): Kallay E, Bajna E, Wrba F, Kriwanek S, Peterlik M, Cross HS. Source: Cancer Detect Prev. 2000; 24(2): 127-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10917132&dopt=Abstract
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Dietary lipids, inflammation, and colon cancer. Author(s): Kuratko CN. Source: Adv Exp Med Biol. 1999; 470: 33-43. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10709672&dopt=Abstract
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Differences of vascular endothelial growth factor (VEGF) expression between liver and abdominal metastases from colon cancer. Implications for the treatment with VEGF inhibitors. Author(s): Cascinu S, Graziano F, Catalano V, Staccioli MP, Barni S, Giordani P, Rossi MC, Baldelli AM, Muretto P, Valenti A, Catalano G. Source: Clin Exp Metastasis. 2000; 18(8): 651-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11827068&dopt=Abstract
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Different molecular events account for butyrate-induced apoptosis in two human colon cancer cell lines. Author(s): Avivi-Green C, Polak-Charcon S, Madar Z, Schwartz B. Source: J Nutr. 2002 July; 132(7): 1812-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12097652&dopt=Abstract
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Differential effects between amphoterin and advanced glycation end products on colon cancer cells. Author(s): Kuniyasu H, Chihara Y, Kondo H. Source: Int J Cancer. 2003 May 10; 104(6): 722-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640679&dopt=Abstract
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Differential effects of retinoic acid on growth and apoptosis in human colon cancer cell lines associated with the induction of retinoic acid receptor beta. Author(s): Lee MO, Han SY, Jiang S, Park JH, Kim SJ. Source: Biochem Pharmacol. 2000 March 1; 59(5): 485-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10660115&dopt=Abstract
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Differential expression of carcinoembryonic antigen (CEA) splice variants in whole blood of colon cancer patients and healthy volunteers: implication for the detection of circulating colon cancer cells. Author(s): Hampton R, Walker M, Marshall J, Juhl H. Source: Oncogene. 2002 November 7; 21(51): 7817-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420218&dopt=Abstract
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Differential expression of Hox A5 in human colon cancer cell differentiation: a quantitative study using real-time RT-PCR. Author(s): Wang Y, Hung C, Koh D, Cheong D, Hooi SC. Source: Int J Oncol. 2001 March; 18(3): 617-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11179495&dopt=Abstract
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Differentiation and reversal of malignant changes in colon cancer through PPARgamma. Author(s): Sarraf P, Mueller E, Jones D, King FJ, DeAngelo DJ, Partridge JB, Holden SA, Chen LB, Singer S, Fletcher C, Spiegelman BM. Source: Nat Med. 1998 September; 4(9): 1046-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9734398&dopt=Abstract
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Diffuse colon cancer with tumor thrombus in the portal vein. Author(s): Nakase H, Kawanami C, Itoh T, Okazaki K, Chiba T, Itani T, Mimura J, Kawasaki T, Komori H. Source: Gastrointest Endosc. 2002 February; 55(2): 239-40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11818930&dopt=Abstract
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Dimethyladamantylmaleimide-induced in vitro and in vivo growth inhibition of human colon cancer Colo205 cells. Author(s): Wang JJ, Chern YT, Chang YF, Liu TY, Chi CW. Source: Anticancer Drugs. 2002 June; 13(5): 533-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12045465&dopt=Abstract
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Disruption of transforming growth factor beta-regulated laminin receptor function by expression of antisense laminin, a chain RNA in human colon cancer cells. Author(s): Chakrabarty S, Liu BR, Rajagopal S. Source: J Cell Physiol. 2001 January; 186(1): 47-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11147813&dopt=Abstract
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Distinct protein kinase C isozymes signal mitogenesis and apoptosis in human colon cancer cells. Author(s): Weller SG, Klein IK, Penington RC, Karnes WE Jr. Source: Gastroenterology. 1999 October; 117(4): 848-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10500067&dopt=Abstract
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Distinct PTEN mutational spectra in hereditary non-polyposis colon cancer syndrome-related endometrial carcinomas compared to sporadic microsatellite unstable tumors. Author(s): Zhou XP, Kuismanen S, Nystrom-Lahti M, Peltomaki P, Eng C. Source: Hum Mol Genet. 2002 February 15; 11(4): 445-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11854177&dopt=Abstract
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Divalent cations modulate human colon cancer cell adhesion. Author(s): Thamilselvan V, Fomby M, Walsh M, Basson MD. Source: J Surg Res. 2003 March; 110(1): 255-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697409&dopt=Abstract
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DNA alkylation-induced phosphorylation of p53 and activation of kinases in colon cancer cells. Author(s): Jaiswal AS, Narayan S. Source: Int J Oncol. 2001 September; 19(3): 613-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11494044&dopt=Abstract
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DNA amplification and chromosomal translocations are accompanied by chromosomal instability: analysis of seven human colon cancer cell lines by comparative genomic hybridization and spectral karyotyping. Author(s): Tsushimi T, Noshima S, Oga A, Esato K, Sasaki K. Source: Cancer Genet Cytogenet. 2001 April 1; 126(1): 34-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11343776&dopt=Abstract
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DNA markers predicting benefit from adjuvant fluorouracil in patients with colon cancer: a molecular study. Author(s): Barratt PL, Seymour MT, Stenning SP, Georgiades I, Walker C, Birbeck K, Quirke P; UKCCCR AXIS trial collaborators. Adjuvant X-ray and Fluorouracil Infusion Study. Source: Lancet. 2002 November 2; 360(9343): 1381-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12423985&dopt=Abstract
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DNA repair defects in colon cancer. Author(s): Jiricny J, Marra G. Source: Curr Opin Genet Dev. 2003 February; 13(1): 61-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573437&dopt=Abstract
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Docosahexaenoic acid is a potent inducer of apoptosis in HT-29 colon cancer cells. Author(s): Chen ZY, Istfan NW. Source: Prostaglandins Leukot Essent Fatty Acids. 2000 November; 63(5): 301-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11090257&dopt=Abstract
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Does physical activity prevent cancer? Evidence suggests protection against colon cancer and probably breast cancer. Author(s): Batty D, Thune I. Source: Bmj. 2000 December 9; 321(7274): 1424-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11110720&dopt=Abstract
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Double cancer (lung and colon cancer) that showed complete remission with irinotecan and cisplatin combined chemotherapy. Author(s): Kaneki T, Koizumi T, Kawashima A, Tsushima K, Kubo K, Fujimoto K, Honda T, Akamatsu T. Source: J Gastroenterol. 2000; 35(11): 864-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11085497&dopt=Abstract
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Down regulation of the expression of the p110, p85 and p55 subunits of phosphatidylinositol 3-kinase during colon cancer cell anchorage-independent growth. Author(s): Yeates LC, Gallegos A, Kozikowski AP, Powis G. Source: Anticancer Res. 1999 September-October; 19(5B): 4171-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10628371&dopt=Abstract
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Downregulation of survivin expression by induction of the effector cell protease receptor-1 reduces tumor growth potential and results in an increased sensitivity to anticancer agents in human colon cancer. Author(s): Yamamoto T, Manome Y, Nakamura M, Tanigawa N. Source: Eur J Cancer. 2002 November; 38(17): 2316-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441269&dopt=Abstract
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Downregulation of urokinase plasminogen activator receptor expression inhibits Erk signalling with concomitant suppression of invasiveness due to loss of uPAR-beta1 integrin complex in colon cancer cells. Author(s): Ahmed N, Oliva K, Wang Y, Quinn M, Rice G. Source: Br J Cancer. 2003 July 21; 89(2): 374-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865932&dopt=Abstract
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Drg-1 as a differentiation-related, putative metastatic suppressor gene in human colon cancer. Author(s): Guan RJ, Ford HL, Fu Y, Li Y, Shaw LM, Pardee AB. Source: Cancer Res. 2000 February 1; 60(3): 749-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10676663&dopt=Abstract
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Drug resistance in colon cancer. Author(s): Gorlick R, Bertino JR. Source: Semin Oncol. 1999 December; 26(6): 606-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10606253&dopt=Abstract
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E2F-1 up-regulates c-Myc and p14(ARF) and induces apoptosis in colon cancer cells. Author(s): Elliott MJ, Dong YB, Yang H, McMasters KM. Source: Clin Cancer Res. 2001 November; 7(11): 3590-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11705881&dopt=Abstract
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Early tumor growth in metastatic organs influenced by the microenvironment is an important factor which provides organ specificity of colon cancer metastasis. Author(s): Hara Y, Ogata Y, Shirouzu K. Source: J Exp Clin Cancer Res. 2000 December; 19(4): 497-504. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11277329&dopt=Abstract
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Eating frequency and the risk of colon cancer. Author(s): Coates AO, Potter JD, Caan BJ, Edwards SL, Slattery ML. Source: Nutr Cancer. 2002; 43(2): 121-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588690&dopt=Abstract
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Ectopic expression of eIF-4E in human colon cancer cells promotes the stimulation of adhesion molecules by transforming growth factorbeta. Author(s): Rajagopal S, Chakrabarty S. Source: Cell Commun Adhes. 2001; 8(2): 87-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771728&dopt=Abstract
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Editor's comment: colon cancer carrier screening enters the genetic testing arena. Author(s): Gilbert F. Source: Genet Test. 2002 Winter; 6(4): 271-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537650&dopt=Abstract
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Edrecolomab (Panorex) as adjuvant therapy for stage II colon cancer. Author(s): Gambill BD. Source: Clin Colorectal Cancer. 2001 May; 1(1): 16-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445374&dopt=Abstract
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Effect of 2'-O-methyl antisense ORNs on expression of thymidylate synthase in human colon cancer RKO cells. Author(s): Schmitz JC, Yu D, Agrawal S, Chu E. Source: Nucleic Acids Res. 2001 January 15; 29(2): 415-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11139611&dopt=Abstract
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Effect of combination therapy with matrix metalloproteinase inhibitor MMI-166 and mitomycin C on the growth and liver metastasis of human colon cancer. Author(s): Ohta M, Konno H, Tanaka T, Baba M, Kamiya K, Oba K, Kaneko T, Syouji T, Igarashi A, Nakamura S. Source: Jpn J Cancer Res. 2001 June; 92(6): 688-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11429059&dopt=Abstract
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Effect of nifedipine in metastatic colon cancer with DNA mismatch repair gene defect. Author(s): Yang JL, Friedlander ML. Source: Lancet. 2001 June 2; 357(9270): 1767-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11403819&dopt=Abstract
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Effect of structural analogues of propionate and butyrate on colon cancer cell growth. Author(s): Milovic V, Teller IC, Turchanowa L, Caspary WF, Stein J. Source: Int J Colorectal Dis. 2000 November; 15(5-6): 264-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11151428&dopt=Abstract
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Effectiveness of adjuvant fluorouracil in clinical practice: a population-based cohort study of elderly patients with stage III colon cancer. Author(s): Iwashyna TJ, Lamont EB. Source: J Clin Oncol. 2002 October 1; 20(19): 3992-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12351596&dopt=Abstract
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Effectiveness of adjuvant fluorouracil in elderly colon cancer patients: the internal and external validity of nonrandomized research design. Author(s): Apolone G, Cavuto S, Torri V, la Vecchia C. Source: J Clin Oncol. 2003 May 1; 21(9): 1892; Author Reply 1893. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12721271&dopt=Abstract
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Effects of a hyaluronan-based membrane (Seprafilm) on intraperitoneally disseminated human colon cancer cell growth in a nude mouse model. Author(s): Hubbard SC, Burns JW. Source: Dis Colon Rectum. 2002 March; 45(3): 334-41; Discussion 341-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12068190&dopt=Abstract
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Effects of deoxycholate on human colon cancer cells: apoptosis or proliferation. Author(s): Milovic V, Teller IC, Faust D, Caspary WF, Stein J. Source: Eur J Clin Invest. 2002 January; 32(1): 29-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11851724&dopt=Abstract
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Effects of genetic blockade of the insulin-like growth factor receptor in human colon cancer cell lines. Author(s): Adachi Y, Lee CT, Coffee K, Yamagata N, Ohm JE, Park KH, Dikov MM, Nadaf SR, Arteaga CL, Carbone DP. Source: Gastroenterology. 2002 October; 123(4): 1191-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12360481&dopt=Abstract
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Efficacy of oral UFT plus leucovorin therapy for colon cancer with ovarian and multiple liver metastases: report of two cases. Author(s): mukai M, Moriya H, Himeno S, Oida Y, mukohyama S, Nishi T, Nakasaki H, Satoh S, Makuuchi H. Source: Oncol Rep. 2001 September-October; 8(5): 1079-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11496320&dopt=Abstract
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Efficient intracellular delivery of 5-fluorodeoxyuridine into colon cancer cells by targeted immunoliposomes. Author(s): Koning GA, Kamps JA, Scherphof GL. Source: Cancer Detect Prev. 2002; 26(4): 299-307. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12430634&dopt=Abstract
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Elimination of colon cancer in germ-free transforming growth factor beta 1-deficient mice. Author(s): Engle SJ, Ormsby I, Pawlowski S, Boivin GP, Croft J, Balish E, Doetschman T. Source: Cancer Res. 2002 November 15; 62(22): 6362-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438215&dopt=Abstract
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En bloc pancreaticoduodenectomy for right colon cancer invading adjacent organs. Author(s): Ann Intern Med. 2002 Mar 5;136(5):I19 Source: J Surg Oncol. 2002 March; 79(3): 194-7; Discussion 198. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11874328
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Endometrial and colorectal tumors from patients with hereditary nonpolyposis colon cancer display different patterns of microsatellite instability. Author(s): Kuismanen SA, Moisio AL, Schweizer P, Truninger K, Salovaara R, Arola J, Butzow R, Jiricny J, Nystrom-Lahti M, Peltomaki P. Source: Am J Pathol. 2002 June; 160(6): 1953-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12057899&dopt=Abstract
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Endophthalmitis with brain, lung, and liver abscesses associated with an occult colon cancer. Author(s): Matsushita M, Hajiro K, Okazaki K, Takakuwa H, Nishio A. Source: Am J Gastroenterol. 2000 December; 95(12): 3664-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11151925&dopt=Abstract
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Endostatin exhibits a direct antitumor effect in addition to its antiangiogenic activity in colon cancer cells. Author(s): Dkhissi F, Lu H, Soria C, Opolon P, Griscelli F, Liu H, Khattar P, Mishal Z, Perricaudet M, Li H. Source: Hum Gene Ther. 2003 July 1; 14(10): 997-1008. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869217&dopt=Abstract
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Endothelial cell apoptosis is inhibited by a soluble factor secreted by human colon cancer cells. Author(s): Liu W, Davis DW, Ramirez K, McConkey DJ, Ellis LM. Source: Int J Cancer. 2001 April 1; 92(1): 26-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11279602&dopt=Abstract
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Endothelin-receptor antagonists are proapoptotic and antiproliferative in human colon cancer cells. Author(s): Peduto Eberl L, Bovey R, Juillerat-Jeanneret L. Source: Br J Cancer. 2003 March 10; 88(5): 788-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618891&dopt=Abstract
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Enhancement of radiation therapy by tumor necrosis factor alpha in human colon cancer using a bispecific antibody. Author(s): Azria D, Dorvillius M, Gourgou S, Martineau P, Robert B, Pugniere M, Delard R, Ychou M, Dubois JB, Pelegrin A. Source: Int J Radiat Oncol Biol Phys. 2003 April 1; 55(5): 1363-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654449&dopt=Abstract
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Environmental factors of temperature, humidity, serum accumulation, and cell seeding increase colon cancer cell adhesion in vitro, with partial characterization of the serum component responsible for pressure-stimulated adhesion. Author(s): Kavic SM, Basson MD. Source: J Surg Res. 2001 June 15; 98(2): 89-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11397124&dopt=Abstract
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Epithelial cyclooxygenase-2 expression: a model for pathogenesis of colon cancer. Author(s): Arbabi S, Rosengart MR, Garcia I, Jelacic S, Maier RV. Source: J Surg Res. 2001 May 1; 97(1): 60-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11319881&dopt=Abstract
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Erosion of psoriatic plaques: an uncommon side-effect of neoadjuvant 5-fluorouracil treatment of colon cancer. Author(s): Wetzig T, Beckheinrich P, Rytter M, Haustein UF. Source: Br J Dermatol. 2002 October; 147(4): 824-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12366448&dopt=Abstract
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ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and follow-up of colon cancer. Author(s): ESMO.. Source: Ann Oncol. 2001 August; 12(8): 1053-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11583182&dopt=Abstract
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Establishment and characterization of acquired resistance to the farnesyl protein transferase inhibitor R115777 in a human colon cancer cell line. Author(s): Smith V, Rowlands MG, Barrie E, Workman P, Kelland LR. Source: Clin Cancer Res. 2002 June; 8(6): 2002-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12060646&dopt=Abstract
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Estrogen and colon cancer: current issues. Author(s): al-Azzawi F, Wahab M. Source: Climacteric. 2002 March; 5(1): 3-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11974557&dopt=Abstract
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Estrogen receptor beta mRNA in colon cancer cells: growth effects of estrogen and genistein. Author(s): Arai N, Strom A, Rafter JJ, Gustafsson JA. Source: Biochem Biophys Res Commun. 2000 April 13; 270(2): 425-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10753641&dopt=Abstract
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Estrogens reduce and withdrawal of estrogens increase risk of microsatellite instability-positive colon cancer. Author(s): Slattery ML, Potter JD, Curtin K, Edwards S, Ma KN, Anderson K, Schaffer D, Samowitz WS. Source: Cancer Res. 2001 January 1; 61(1): 126-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11196149&dopt=Abstract
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Eubacterium bacteremia and colon cancer. Author(s): Sungkanuparph S, Chansirikarnjana S, Vorachit M. Source: Scand J Infect Dis. 2002; 34(12): 941-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587635&dopt=Abstract
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Evaluating the impact of population changes in diet, physical activity, and weight status on population risk for colon cancer (United States). Author(s): Cronin KA, Krebs-Smith SM, Feuer EJ, Troiano RP, Ballard-Barbash R. Source: Cancer Causes Control. 2001 May; 12(4): 305-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11456226&dopt=Abstract
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Evaluation of microsatellite instability and immunohistochemistry for the prediction of germ-line MSH2 and MLH1 mutations in hereditary nonpolyposis colon cancer families. Author(s): Wahlberg SS, Schmeits J, Thomas G, Loda M, Garber J, Syngal S, Kolodner RD, Fox E. Source: Cancer Res. 2002 June 15; 62(12): 3485-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067992&dopt=Abstract
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Evaluation of telomerase in the development and progression of colon cancer. Author(s): Boldrini L, Faviana P, Gisfredi S, Zucconi Y, Di Quirico D, Donati V, Berti P, Spisni R, Galleri D, Materazzi G, Basolo F, Miccoli P, Pingitore R, Fontanini G. Source: Int J Mol Med. 2002 November; 10(5): 589-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12373297&dopt=Abstract
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Evaluation of telomerase mRNA (hTERT) in colon cancer. Author(s): Boldrini L, Faviana P, Gisfredi S, Zucconi Y, Di Quirico D, Donati V, Berti P, Spisni R, Galleri D, Materazzi G, Basolo F, Miccoli P, Pingitore R, Fontanini G. Source: Int J Oncol. 2002 September; 21(3): 493-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12168091&dopt=Abstract
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Evidence that APC regulates survivin expression: a possible mechanism contributing to the stem cell origin of colon cancer. Author(s): Zhang T, Otevrel T, Gao Z, Gao Z, Ehrlich SM, Fields JZ, Boman BM. Source: Cancer Res. 2001 December 15; 61(24): 8664-7. Erratum In: Cancer Res 2002 Dec 15; 62(24): 7379. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751382&dopt=Abstract
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Experimental and clinicopathologic studies on the function of the HGF receptor in human colon cancer metastasis. Author(s): Fazekas K, Csuka O, Koves I, Raso E, Timar J. Source: Clin Exp Metastasis. 2000; 18(8): 639-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11827067&dopt=Abstract
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Experimental evidences on the potential of prebiotic fructans to reduce the risk of colon cancer. Author(s): Pool-Zobel B, van Loo J, Rowland I, Roberfroid MB. Source: Br J Nutr. 2002 May; 87 Suppl 2: S273-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088529&dopt=Abstract
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Exposure to a deuterated analogue of phenylbutyrate retards S-phase progression in HT-29 colon cancer cells. Author(s): Clarke KO, Ludeman SM, Springer JB, Colvin OM, Lea MA, Harrison LE. Source: J Pharm Sci. 2002 April; 91(4): 1054-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11948544&dopt=Abstract
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Expression of estrogen receptor (ER) subtypes and ERbeta isoforms in colon cancer. Author(s): Campbell-Thompson M, Lynch IJ, Bhardwaj B. Source: Cancer Res. 2001 January 15; 61(2): 632-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11212261&dopt=Abstract
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Expression of gelatinase-A (MMP-2) in human colon cancer and normal colon mucosa. Author(s): Papadopoulou S, Scorilas A, Arnogianaki N, Papapanayiotou B, Tzimogiani A, Agnantis N, Talieri M. Source: Tumour Biol. 2001 November-December; 22(6): 383-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11786732&dopt=Abstract
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Expression of GRP and its receptor in well-differentiated colon cancer cells correlates with the presence of focal adhesion kinase phosphorylated at tyrosines 397 and 407. Author(s): Matkowskyj KA, Keller K, Glover S, Kornberg L, Tran-Son-Tay R, Benya RV. Source: J Histochem Cytochem. 2003 August; 51(8): 1041-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12871985&dopt=Abstract
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Expression of H type 1 antigen of ABO histo-blood group in normal colon and aberrant expressions of H type 2 and H type 3/4 antigens in colon cancer. Author(s): Fujitani N, Liu Y, Toda S, Shirouzu K, Okamura T, Kimura H. Source: Glycoconj J. 2000 May; 17(5): 331-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11261842&dopt=Abstract
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Expression of human intestinal mucin is modulated by the beta-galactoside binding protein galectin-3 in colon cancer. Author(s): Dudas SP, Yunker CK, Sternberg LR, Byrd JC, Bresalier RS. Source: Gastroenterology. 2002 September; 123(3): 817-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198708&dopt=Abstract
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Expression of the antiangiogenic factor 16K hPRL in human HCT116 colon cancer cells inhibits tumor growth in Rag1(-/-) mice. Author(s): Bentzien F, Struman I, Martini JF, Martial J, Weiner R. Source: Cancer Res. 2001 October 1; 61(19): 7356-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11585777&dopt=Abstract
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Expression of the gut-enriched Kruppel-like factor (Kruppel-like factor 4) gene in the human colon cancer cell line RKO is dependent on CDX2. Author(s): Dang DT, Mahatan CS, Dang LH, Agboola IA, Yang VW. Source: Oncogene. 2001 August 9; 20(35): 4884-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11521200&dopt=Abstract
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Expression of the hMSH6 mismatch-repair protein in colon cancer and HeLa cells. Author(s): Klingler H, Hemmerle C, Bannwart F, Haider R, Cattaruzza MS, Marra G. Source: Swiss Med Wkly. 2002 February 9; 132(5-6): 57-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11971198&dopt=Abstract
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Expression of thrombospondin-1 inversely correlated with tumor vascularity and hematogenous metastasis in colon cancer. Author(s): Maeda K, Nishiguchi Y, Kang SM, Yashiro M, Onoda N, Sawada T, Ishikawa T, Hirakawa K. Source: Oncol Rep. 2001 July-August; 8(4): 763-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11410779&dopt=Abstract
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Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Author(s): Iizaka M, Furukawa Y, Tsunoda T, Akashi H, Ogawa M, Nakamura Y. Source: Biochem Biophys Res Commun. 2002 March 29; 292(2): 498-512. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11906190&dopt=Abstract
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Extensive methylation of hMLH1 promoter region predominates in proximal colon cancer with microsatellite instability. Author(s): Miyakura Y, Sugano K, Konishi F, Ichikawa A, Maekawa M, Shitoh K, Igarashi S, Kotake K, Koyama Y, Nagai H. Source: Gastroenterology. 2001 December; 121(6): 1300-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11729109&dopt=Abstract
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Factors influencing intention to obtain a genetic test for colon cancer risk: a population-based study. Author(s): Bunn JY, Bosompra K, Ashikaga T, Flynn BS, Worden JK. Source: Prev Med. 2002 June; 34(6): 567-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12052015&dopt=Abstract
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Familial adenomatous polyposis as a precancerosis of colon cancer. Author(s): Vavra P, Dostalik J, Martinek L, Zonca P, Plevova P, Kohoutova M, Stekrova J. Source: Bratisl Lek Listy. 2002; 103(11): 418-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585356&dopt=Abstract
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Familial adenomatous polyposis, hereditary nonpolyposis colon cancer, and familial risk: what are the implications for the surgeon? Author(s): Thorson AG, Faria J. Source: Surg Oncol Clin N Am. 2000 October; 9(4): 683-97; Discussion 699-701. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11008233&dopt=Abstract
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Family history of colon cancer: what does it mean and how is it useful? Author(s): Keku TO, Millikan RC, Martin C, Rahkra-Burris TK, Sandler RS. Source: Am J Prev Med. 2003 February; 24(2): 170-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568823&dopt=Abstract
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Fas ligand expression in primary colon adenocarcinomas: evidence that the Fas counterattack is a prevalent mechanism of immune evasion in human colon cancer. Author(s): O'Connell J, Bennett MW, O'Sullivan GC, Roche D, Kelly J, Collins JK, Shanahan F. Source: J Pathol. 1998 November; 186(3): 240-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10211111&dopt=Abstract
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Fat and dietary fiber intake and colon cancer mortality: a chronological comparison between Japan and the United States. Author(s): Honda T, Kai I, Ohi G. Source: Nutr Cancer. 1999; 33(1): 95-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10227050&dopt=Abstract
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FDG PET evaluation of residual masses and regrowth of abdominal lymph node metastases from colon cancer compared with CT during chemotherapy. Author(s): Yoshioka T, Fukuda H, Fujiwara T, Iwata R, Ido T, Murakawa Y, Gamo M, Ishioka C, Kanamaru R. Source: Clin Nucl Med. 1999 April; 24(4): 261-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10466523&dopt=Abstract
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Fiber and colon cancer: do we need to take a new look at an old theory? Author(s): Trissler RJ. Source: J Am Diet Assoc. 1999 September; 99(9): 1045. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10507915&dopt=Abstract
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Fiber-derived butyrate and the prevention of colon cancer. Author(s): Hassig CA, Tong JK, Schreiber SL. Source: Chem Biol. 1997 November; 4(11): 783-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9384528&dopt=Abstract
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First results for resetting the antitumor immune response by immune corrective surgery in colon cancer. Author(s): Barbera-Guillem E, Arnold MW, Nelson MB, Martin EW Jr. Source: Am J Surg. 1998 October; 176(4): 339-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9817251&dopt=Abstract
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Fluoropyrimidine resistance in colon cancer. Author(s): Gorlick R, Banerjee D. Source: Expert Rev Anticancer Ther. 2002 August; 2(4): 409-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12647984&dopt=Abstract
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Fluorouracil and leucovorin with or without interferon alfa-2a as adjuvant treatment, in patients with high-risk colon cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group. Author(s): Fountzilas G, Zisiadis A, Dafni U, Konstantaras C, Hatzitheoharis G, Papavramidis S, Bousoulegas A, Basdanis G, Giannoulis E, Dokmetzioglou J, Katsohis C, Nenopoulou E, Karvounis N, Briassoulis E, Aravantinos G, Kosmidis P, Skarlos D, Pavlidis N. Source: Oncology. 2000 April; 58(3): 227-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10765125&dopt=Abstract
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Focus on colon cancer. Author(s): Markowitz SD, Dawson DM, Willis J, Willson JK. Source: Cancer Cell. 2002 April; 1(3): 233-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086859&dopt=Abstract
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Folate and chemoprevention of colorectal cancer: Is 5-methyl-tetrahydrofolate an active antiproliferative agent in folate-treated colon-cancer cells? Author(s): Akoglu B, Faust D, Milovic V, Stein J. Source: Nutrition. 2001 July-August; 17(7-8): 652-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11448589&dopt=Abstract
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Folate and colon cancer: a fascinating puzzle we have yet to complete. Author(s): Mason JB. Source: Clin Nutr. 1998 April; 17(2): 41-3. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10205315&dopt=Abstract
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Folic acid inhibition of EGFR-mediated proliferation in human colon cancer cell lines. Author(s): Jaszewski R, Khan A, Sarkar FH, Kucuk O, Tobi M, Zagnoon A, Dhar R, Kinzie J, Majumdar AP. Source: Am J Physiol. 1999 December; 277(6 Pt 1): C1142-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10600765&dopt=Abstract
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Follow-up of colon cancer: detection of liver metastases: benefit and periodicity. Author(s): de Goede E, Filez L, Janssens J, Van Cutsem E. Source: Acta Gastroenterol Belg. 1998 January-March; 61(1): 8-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9629764&dopt=Abstract
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Fourth International Conference on Colorectal Cancer: adjuvant treatment of colon cancer--introduction. Author(s): Piedbois P. Source: Semin Oncol. 2001 February; 28(1 Suppl 1): 1-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11273583&dopt=Abstract
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Frameshift mutations and a length polymorphism in the hMSH3 gene and the spectrum of microsatellite instability in sporadic colon cancer. Author(s): Orimo H, Nakajima E, Ikejima M, Emi M, Shimada T. Source: Jpn J Cancer Res. 1999 December; 90(12): 1310-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10665647&dopt=Abstract
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Frequent loss of hMLH1 by promoter hypermethylation leads to microsatellite instability in adenomatous polyps of patients with a single first-degree member affected by colon cancer. Author(s): Ricciardiello L, Goel A, Mantovani V, Fiorini T, Fossi S, Chang DK, Lunedei V, Pozzato P, Zagari RM, De Luca L, Fuccio L, Martinelli GN, Roda E, Boland CR, Bazzoli F. Source: Cancer Res. 2003 February 15; 63(4): 787-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591727&dopt=Abstract
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Frequent nitric oxide synthase-2 expression in human colon adenomas: implication for tumor angiogenesis and colon cancer progression. Author(s): Ambs S, Merriam WG, Bennett WP, Felley-Bosco E, Ogunfusika MO, Oser SM, Klein S, Shields PG, Billiar TR, Harris CC. Source: Cancer Res. 1998 January 15; 58(2): 334-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9443414&dopt=Abstract
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Frequent somatic mutations in serine/threonine kinase 11/Peutz-Jeghers syndrome gene in left-sided colon cancer. Author(s): Dong SM, Kim KM, Kim SY, Shin MS, Na EY, Lee SH, Park WS, Yoo NJ, Jang JJ, Yoon CY, Kim JW, Kim SY, Yang YM, Kim SH, Kim CS, Lee JY. Source: Cancer Res. 1998 September 1; 58(17): 3787-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9731485&dopt=Abstract
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Functional analysis of MLH1 mutations linked to hereditary nonpolyposis colon cancer. Author(s): Nystrom-Lahti M, Perrera C, Raschle M, Panyushkina-Seiler E, Marra G, Curci A, Quaresima B, Costanzo F, D'Urso M, Venuta S, Jiricny J. Source: Genes Chromosomes Cancer. 2002 February; 33(2): 160-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11793442&dopt=Abstract
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Functional estrogen receptor beta in colon cancer cells. Author(s): Fiorelli G, Picariello L, Martineti V, Tonelli F, Brandi ML. Source: Biochem Biophys Res Commun. 1999 August 2; 261(2): 521-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10425218&dopt=Abstract
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Functional interaction of lithocholic acid conjugates with M3 muscarinic receptors on a human colon cancer cell line. Author(s): Cheng K, Chen Y, Zimniak P, Raufman JP, Xiao Y, Frucht H. Source: Biochim Biophys Acta. 2002 October 9; 1588(1): 48-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379313&dopt=Abstract
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Further investigation of the modifying effect of various chemopreventive agents on apoptosis and cell proliferation in human colon cancer cells. Author(s): Zheng Q, Hirose Y, Yoshimi N, Murakami A, Koshimizu K, Ohigashi H, Sakata K, Matsumoto Y, Sayama Y, Mori H. Source: J Cancer Res Clin Oncol. 2002 October; 128(10): 539-46. Epub 2002 September 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384797&dopt=Abstract
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Future directions in the adjuvant treatment of colon cancer. Author(s): Mamounas EP, Wieand HS, Jones J, Wickerham DL, Wolmark N. Source: Oncology (Huntingt). 1997 September; 11(9 Suppl 10): 44-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9348567&dopt=Abstract
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GABA content and GAD activity in colon tumors taken from patients with colon cancer or from xenografted human colon cancer cells growing as s.c. tumors in athymic nu/nu mice. Author(s): Kleinrok Z, Matuszek M, Jesipowicz J, Matuszek B, Opolski A, Radzikowski C. Source: J Physiol Pharmacol. 1998 June; 49(2): 303-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9670113&dopt=Abstract
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Galectin-8 expression decreases in cancer compared with normal and dysplastic human colon tissue and acts significantly on human colon cancer cell migration as a suppressor. Author(s): Nagy N, Bronckart Y, Camby I, Legendre H, Lahm H, Kaltner H, Hadari Y, Van Ham P, Yeaton P, Pector JC, Zick Y, Salmon I, Danguy A, Kiss R, Gabius HJ. Source: Gut. 2002 March; 50(3): 392-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11839721&dopt=Abstract
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Gene expression profiling of human colon cancer cells following inhibition of signal transduction by 17-allylamino-17-demethoxygeldanamycin, an inhibitor of the hsp90 molecular chaperone. Author(s): Clarke PA, Hostein I, Banerji U, Stefano FD, Maloney A, Walton M, Judson I, Workman P. Source: Oncogene. 2000 August 24; 19(36): 4125-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10962573&dopt=Abstract
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Gene therapy for colon cancer. Author(s): Zwacka RM, Dunlop MG. Source: Hematol Oncol Clin North Am. 1998 June; 12(3): 595-615. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9684100&dopt=Abstract
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Gene therapy strategies for colon cancer. Author(s): Chung-Faye GA, Kerr DJ, Young LS, Searle PF. Source: Mol Med Today. 2000 February; 6(2): 82-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10652481&dopt=Abstract
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Gene-specific repair of gamma-ray-induced DNA strand breaks in colon cancer cells: no coupling to transcription and no removal from the mitochondrial genome. Author(s): May A, Bohr VA. Source: Biochem Biophys Res Commun. 2000 March 16; 269(2): 433-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10708571&dopt=Abstract
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Genetic and epigenetic alterations in colon cancer. Author(s): Grady WM, Markowitz SD. Source: Annu Rev Genomics Hum Genet. 2002; 3: 101-28. Epub 2002 April 15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142355&dopt=Abstract
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Genetic changes of hOGG1 and the activity of oh8Gua glycosylase in colon cancer. Author(s): Park YJ, Choi EY, Choi JY, Park JG, You HJ, Chung MH. Source: Eur J Cancer. 2001 February; 37(3): 340-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11239755&dopt=Abstract
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Genetic disruption of PPARdelta decreases the tumorigenicity of human colon cancer cells. Author(s): Park BH, Vogelstein B, Kinzler KW. Source: Proc Natl Acad Sci U S A. 2001 February 27; 98(5): 2598-603. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11226285&dopt=Abstract
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Genetic polymorphisms in carcinogen metabolism and their association to hereditary nonpolyposis colon cancer. Author(s): Moisio AL, Sistonen P, Mecklin JP, Jarvinen H, Peltomaki P. Source: Gastroenterology. 1998 December; 115(6): 1387-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9834266&dopt=Abstract
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Genetic polymorphisms in the cytochrome P450 1A1, glutathione S-transferase M1 and T1, and susceptibility to colon cancer. Author(s): Ye Z, Parry JM. Source: Teratog Carcinog Mutagen. 2002; 22(5): 385-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210502&dopt=Abstract
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Genetic profiling of colon cancer. Author(s): Neibergs HL, Hein DW, Spratt JS. Source: J Surg Oncol. 2002 August; 80(4): 204-13. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210035&dopt=Abstract
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Genetic reprogramming in pathways of colonic cell maturation induced by short chain fatty acids: comparison with trichostatin A, sulindac, and curcumin and implications for chemoprevention of colon cancer. Author(s): Mariadason JM, Corner GA, Augenlicht LH. Source: Cancer Res. 2000 August 15; 60(16): 4561-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10969808&dopt=Abstract
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Genetic testing for colon cancer: joint statement of the American College of Medical Genetics and American Society of Human Genetics. Joint Test and Technology Transfer Committee Working Group. Author(s): Joint Test and Technology Transfer Committee Working Group, American College of Medical Genetics, 9650 Rockville Pike, Bethesda, MD 20814-3998, United States.. Source: Genet Med. 2000 November-December; 2(6): 362-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11339660&dopt=Abstract
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Genetic testing for high-risk colon cancer patients. Author(s): Grady WM. Source: Gastroenterology. 2003 May; 124(6): 1574-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12761718&dopt=Abstract
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Genetic testing in families with hereditary nonpolyposis colon cancer. Author(s): Lerman C, Hughes C, Trock BJ, Myers RE, Main D, Bonney A, Abbaszadegan MR, Harty AE, Franklin BA, Lynch JF, Lynch HT. Source: Jama. 1999 May 5; 281(17): 1618-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10235155&dopt=Abstract
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Genetic testings for cancer: the surgeon's critical role. Familial colon cancer. Author(s): Vogelstein B. Source: J Am Coll Surg. 1999 January; 188(1): 74-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9915247&dopt=Abstract
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Genetics of hereditary colon cancer - a basis for prevention? Author(s): Muller HH, Heinimann K, Dobbie Z. Source: Eur J Cancer. 2000 June; 36(10): 1215-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10882859&dopt=Abstract
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Genetics of hereditary colon cancer: a model for prevention. Author(s): Stern H, Lagarde A. Source: Can J Surg. 1998 October; 41(5): 345-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9793501&dopt=Abstract
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Genistein induces apoptosis and topoisomerase II-mediated DNA breakage in colon cancer cells. Author(s): Salti GI, Grewal S, Mehta RR, Das Gupta TK, Boddie AW Jr, Constantinou AI. Source: Eur J Cancer. 2000 April; 36(6): 796-802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10762754&dopt=Abstract
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Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Author(s): Pitti RM, Marsters SA, Lawrence DA, Roy M, Kischkel FC, Dowd P, Huang A, Donahue CJ, Sherwood SW, Baldwin DT, Godowski PJ, Wood WI, Gurney AL, Hillan KJ, Cohen RL, Goddard AD, Botstein D, Ashkenazi A. Source: Nature. 1998 December 17; 396(6712): 699-703. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9872321&dopt=Abstract
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Geraniol, a component of plant essential oils, inhibits growth and polyamine biosynthesis in human colon cancer cells. Author(s): Carnesecchi S, Schneider Y, Ceraline J, Duranton B, Gosse F, Seiler N, Raul F. Source: J Pharmacol Exp Ther. 2001 July; 298(1): 197-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11408542&dopt=Abstract
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Geraniol, a component of plant essential oils, sensitizes human colon cancer cells to 5-fluorouracil treatment. Author(s): Carnesecchi S, Langley K, Exinger F, Gosse F, Raul F. Source: Iarc Sci Publ. 2002; 156: 407-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12484223&dopt=Abstract
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Glutathione and mercapturic acid conjugates of sulofenur and their activity against a human colon cancer cell line. Author(s): Guan X, Hoffman BN, McFarland DC, Gilkerson KK, Dwivedi C, Erickson AK, Bebensee S, Pellegrini J. Source: Drug Metab Dispos. 2002 March; 30(3): 331-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11854154&dopt=Abstract
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Glycine-extended gastrin exerts growth-promoting effects on human colon cancer cells. Author(s): Stepan VM, Sawada M, Todisco A, Dickinson CJ. Source: Mol Med. 1999 March; 5(3): 147-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10404512&dopt=Abstract
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Glycine-extended gastrin promotes the invasiveness of human colon cancer cells. Author(s): Kermorgant S, Lehy T. Source: Biochem Biophys Res Commun. 2001 July 6; 285(1): 136-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11437383&dopt=Abstract
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Growth dependency of human colon cancer xenograft on organ environment is related with their original clinical stage. Author(s): Pocard M, Muleris M, Hamelin R, Salmon RJ, Dutrillaux B, Poupon MF. Source: Anticancer Res. 1998 July-August; 18(4A): 2743-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9703939&dopt=Abstract
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Growth inhibitory effects of 1,25-dihydroxyvitamin D3 and its synthetic analogue, 1alpha,25-dihydroxy-16-ene-23yne-26,27-hexafluoro-19-nor-cholecalcifero l (Ro 256760), on a human colon cancer xenograft. Author(s): Evans SR, Schwartz AM, Shchepotin EI, Uskokovic M, Shchepotin IB. Source: Clin Cancer Res. 1998 November; 4(11): 2869-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9829754&dopt=Abstract
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Growth regulation of human colon cancer cells by epidermal growth factor and 1,25dihydroxyvitamin D3 is mediated by mutual modulation of receptor expression. Author(s): Tong WM, Kallay E, Hofer H, Hulla W, Manhardt T, Peterlik M, Cross HS. Source: Eur J Cancer. 1998 December; 34(13): 2119-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10070321&dopt=Abstract
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Growth response of colon cancer cell lines to selective estrogen receptor modulators. Author(s): Picariello L, Fiorelli G, Martineti V, Tognarini I, Pampaloni B, Tonelli F, Brandi ML. Source: Anticancer Res. 2003 May-June; 23(3B): 2419-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894523&dopt=Abstract
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Growth-promoting effect of muscarinic acetylcholine receptors in colon cancer cells. Author(s): Ukegawa JI, Takeuchi Y, Kusayanagi S, Mitamura K. Source: J Cancer Res Clin Oncol. 2003 May; 129(5): 272-8. Epub 2003 May 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748850&dopt=Abstract
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Harvard Report on Cancer Prevention. Volume 3: prevention of colon cancer in the United States. Author(s): Tomeo CA, Colditz GA, Willett WC, Giovannucci E, Platz E, Rockhill B, Dart H, Hunter DJ. Source: Cancer Causes Control. 1999 June; 10(3): 167-80. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10454062&dopt=Abstract
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Hepatic resection for liver metastasis of sigmoid colon cancer after incomplete percutaneous microwave coagulation therapy. Author(s): Idani H, Narusue M, Kin H, Uda K, Muro M, Kaneko A, Sasaki H, Watanabe K, Takahashi K. Source: Hepatogastroenterology. 2001 January-February; 48(37): 244-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11268974&dopt=Abstract
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Hepatocyte extracellular matrix modulates expression of growth factors and growth factor receptors in human colon cancer cells. Author(s): Zvibel I, Brill S, Halpern Z, Papa M. Source: Exp Cell Res. 1998 November 25; 245(1): 123-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9828107&dopt=Abstract
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Hepatocyte-derived soluble factors regulate proliferation and autocrine growth factor expression in colon cancer cell lines of varying liver-colonizing capability. Author(s): Zvibel I, Brill S, Papa M, Halpern Z. Source: Tumour Biol. 2000 July-August; 21(4): 187-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10867612&dopt=Abstract
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HER 2/neu expression and gene amplification in colon cancer. Author(s): Nathanson DR, Culliford AT 4th, Shia J, Chen B, D'Alessio M, Zeng ZS, Nash GM, Gerald W, Barany F, Paty PB. Source: Int J Cancer. 2003 July 20; 105(6): 796-802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767065&dopt=Abstract
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Hereditary colon cancer genes. Author(s): Grady WM, Markowitz SD. Source: Methods Mol Biol. 2003; 222: 59-83. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710680&dopt=Abstract
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Hereditary nonpolyposis colon cancer. Author(s): Lemire EG. Source: Cmaj. 2001 November 13; 165(10): 1300. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11760969&dopt=Abstract
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Hereditary nonpolyposis colon cancer. Author(s): Cavalieri RJ, Franklin B. Source: Am J Nurs. 1998 October; 98(10): 42-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9803219&dopt=Abstract
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Hereditary nonpolyposis colon cancer: genetic basis, testing, and patient-care issues. Author(s): Jacobs LA. Source: Oncol Nurs Forum. 1998 May; 25(4): 719-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9599355&dopt=Abstract
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Heterocyclic amines, meat intake, and association with colon cancer in a populationbased study. Author(s): Butler LM, Sinha R, Millikan RC, Martin CF, Newman B, Gammon MD, Ammerman AS, Sandler RS. Source: Am J Epidemiol. 2003 March 1; 157(5): 434-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615608&dopt=Abstract
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Heterogeneous induction of apoptosis in colon cancer cells by wild-type p53 gene transfection. Author(s): Namoto M, Yonemitsu Y, Nakagawa K, Hashimoto S, Kaneda Y, Nawata H, Sueishi K. Source: Int J Oncol. 1998 April; 12(4): 777-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9499436&dopt=Abstract
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High gastrin releasing peptide receptor mRNA level is related to tumour dedifferentiation and lymphatic vessel invasion in human colon cancer. Author(s): Saurin JC, Rouault JP, Abello J, Berger F, Remy L, Chayvialle JA. Source: Eur J Cancer. 1999 January; 35(1): 125-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10211100&dopt=Abstract
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High molecular weight phospholipase A2: its occurrence and quantification in human colon cancer and normal mucosa. Author(s): Soydan AS, Tavares IA, Weech PK, Tremblay NM, Bennett A. Source: Adv Exp Med Biol. 1997; 400A: 31-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9547534&dopt=Abstract
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Histopathological identification of colon cancer with microsatellite instability. Author(s): Alexander J, Watanabe T, Wu TT, Rashid A, Li S, Hamilton SR. Source: Am J Pathol. 2001 February; 158(2): 527-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11159189&dopt=Abstract
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HLTF gene silencing in human colon cancer. Author(s): Moinova HR, Chen WD, Shen L, Smiraglia D, Olechnowicz J, Ravi L, Kasturi L, Myeroff L, Plass C, Parsons R, Minna J, Willson JK, Green SB, Issa JP, Markowitz SD. Source: Proc Natl Acad Sci U S A. 2002 April 2; 99(7): 4562-7. Epub 2002 March 19. Erratum In: Proc Natl Acad Sci U S a 2002 June 25; 99(13): 9081. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11904375&dopt=Abstract
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hMSH6 deficiency and inactivation of the alphaE-catenin invasion-suppressor gene in HCT-8 colon cancer cells. Author(s): Vermeulen SJ, Debruyne PR, Marra G, Speleman FP, Boukamp P, Jiricny J, Cuthbert AP, Newbold RF, Nollet FH, van Roy FM, Mareel MM. Source: Clin Exp Metastasis. 1999; 17(8): 663-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10919711&dopt=Abstract
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hOGG1 Ser326Cys polymorphism modifies the significance of the environmental risk factor for colon cancer. Author(s): Kim JI, Park YJ, Kim KH, Kim JI, Song BJ, Lee MS, Kim CN, Chang SH. Source: World J Gastroenterol. 2003 May; 9(5): 956-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717837&dopt=Abstract
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Hormone replacement therapy and colon cancer among members of a health maintenance organization. Author(s): Jacobs EJ, White E, Weiss NS, Heckbert SR, LaCroix A, Barlow WE. Source: Epidemiology. 1999 July; 10(4): 445-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10401882&dopt=Abstract
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Hormone replacement therapy and improved survival among postmenopausal women diagnosed with colon cancer (USA). Author(s): Slattery ML, Anderson K, Samowitz W, Edwards SL, Curtin K, Caan B, Potter JD. Source: Cancer Causes Control. 1999 October; 10(5): 467-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10530618&dopt=Abstract
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How interested is the public in genetic testing for colon cancer susceptibility? Report of a cross-sectional population survey. Author(s): Graham ID, Logan DM, Hughes-Benzie R, Evans WK, Perras H, McAuley LM, Laupacis A, Stern H. Source: Cancer Prev Control. 1998 August; 2(4): 167-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10093629&dopt=Abstract
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How to screen for colon cancer. Author(s): Lieberman D. Source: Annu Rev Med. 1998; 49: 163-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9509256&dopt=Abstract
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HPV16-E7 expression causes fluorodeoxyuridine-mediated radiosensitization in SW620 human colon cancer cells. Author(s): Axelson MD, Davis MA, Ethier SP, Lawrence TS. Source: Neoplasia. 1999 June; 1(2): 177-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10933053&dopt=Abstract
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Human colon cancer cell proliferation mediated by the M3 muscarinic cholinergic receptor. Author(s): Frucht H, Jensen RT, Dexter D, Yang WL, Xiao Y. Source: Clin Cancer Res. 1999 September; 5(9): 2532-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10499630&dopt=Abstract
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Human colon cancer cells deficient in DCC produce abnormal transcripts in progression of carcinogenesis. Author(s): Huerta S, Srivatsan ES, Venkatasan N, Livingston EH. Source: Dig Dis Sci. 2001 September; 46(9): 1884-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11575440&dopt=Abstract
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Human colon cancer cells differ in their sensitivity to curcumin-induced apoptosis and heat shock protects them by inhibiting the release of apoptosis-inducing factor and caspases. Author(s): Rashmi R, Santhosh Kumar TR, Karunagaran D. Source: Febs Lett. 2003 March 13; 538(1-3): 19-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633846&dopt=Abstract
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Human colon cancer cells express multiple glycoprotein ligands for E-selectin. Author(s): Tomlinson J, Wang JL, Barsky SH, Lee MC, Bischoff J, Nguyen M. Source: Int J Oncol. 2000 February; 16(2): 347-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10639580&dopt=Abstract
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Human colon cancer cells express the functional Fas ligand. Author(s): Ding EX, Hizuta A, Morimoto Y, Tanida T, Hongo T, Ishii T, Yamano T, Fujiwara T, Iwagaki H, Tanaka N. Source: Res Commun Mol Pathol Pharmacol. 1998 July; 101(1): 13-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9755840&dopt=Abstract
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Human colon cancer cells surviving high doses of cisplatin or oxaliplatin in vitro are not defective in DNA mismatch repair proteins. Author(s): Sergent C, Franco N, Chapusot C, Lizard-Nacol S, Isambert N, Correia M, Chauffert B. Source: Cancer Chemother Pharmacol. 2002 June; 49(6): 445-52. Epub 2002 April 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107548&dopt=Abstract
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Human colon cancer produces a factor which induces the proliferation of venous endothelial cells. Author(s): Iwasaki K, Yamamoto M, Minami S, Komuta K, Yamaguchi J, Furui J, Kanematsu T. Source: Oncol Rep. 2001 September-October; 8(5): 1057-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11496316&dopt=Abstract
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Huntingtin-interacting protein 1 is overexpressed in prostate and colon cancer and is critical for cellular survival. Author(s): Rao DS, Hyun TS, Kumar PD, Mizukami IF, Rubin MA, Lucas PC, Sanda MG, Ross TS. Source: J Clin Invest. 2002 August; 110(3): 351-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163454&dopt=Abstract
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Hydroxylamine-containing inhibitors of polyamine biosynthesis and impairment of colon cancer cell growth. Author(s): Milovica V, Turchanowa L, Khomutov AR, Khomutov RM, Caspary WF, Stein J. Source: Biochem Pharmacol. 2001 January 15; 61(2): 199-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11163334&dopt=Abstract
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Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Author(s): Cunningham JM, Christensen ER, Tester DJ, Kim CY, Roche PC, Burgart LJ, Thibodeau SN. Source: Cancer Res. 1998 August 1; 58(15): 3455-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9699680&dopt=Abstract
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Identification of metastasis-associated genes by transcriptional profiling of metastatic versus non-metastatic colon cancer cell lines. Author(s): De Lange R, Burtscher H, Jarsch M, Weidle UH. Source: Anticancer Res. 2001 July-August; 21(4A): 2329-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11724290&dopt=Abstract
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Identification of nuclear matrix protein alterations associated with human colon cancer. Author(s): Brunagel G, Vietmeier BN, Bauer AJ, Schoen RE, Getzenberg RH. Source: Cancer Res. 2002 April 15; 62(8): 2437-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11956108&dopt=Abstract
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Identification of objective pathological prognostic determinants and models of prognosis in Dukes' B colon cancer. Author(s): Petersen VC, Baxter KJ, Love SB, Shepherd NA. Source: Gut. 2002 July; 51(1): 65-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12077094&dopt=Abstract
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Identification of Src transformation fingerprint in human colon cancer. Author(s): Malek RL, Irby RB, Guo QM, Lee K, Wong S, He M, Tsai J, Frank B, Liu ET, Quackenbush J, Jove R, Yeatman TJ, Lee NH. Source: Oncogene. 2002 October 17; 21(47): 7256-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12370817&dopt=Abstract
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Identifying patients with T3-T4 node-negative colon cancer at high risk of recurrence. Author(s): Burdy G, Panis Y, Alves A, Nemeth J, Lavergne-Slove A, Valleur P. Source: Dis Colon Rectum. 2001 November; 44(11): 1682-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11711742&dopt=Abstract
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Immunity to the alpha(1,3)galactosyl epitope provides protection in mice challenged with colon cancer cells expressing alpha(1,3)galactosyl-transferase: a novel suicide gene for cancer gene therapy. Author(s): Unfer RC, Hellrung D, Link CJ Jr. Source: Cancer Res. 2003 March 1; 63(5): 987-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615713&dopt=Abstract
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Immunohistochemical analyses of colon cancer in I1307K APC mutation carriers compared with noncarriers. Author(s): Fidder HH, Chen-Shtoyerman R, Barshack I, Onaca N, Goldberg I, Rath P, Theodor L, Bar-Meir S, Friedman E. Source: Dig Dis Sci. 2003 June; 48(6): 1102-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822869&dopt=Abstract
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Impact of diabetes mellitus on outcomes in patients with colon cancer. Author(s): Meyerhardt JA, Catalano PJ, Haller DG, Mayer RJ, Macdonald JS, Benson AB 3rd, Fuchs CS. Source: J Clin Oncol. 2003 February 1; 21(3): 433-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560431&dopt=Abstract
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Impact of insulin-like growth factor receptor-I function on angiogenesis, growth, and metastasis of colon cancer. Author(s): Reinmuth N, Fan F, Liu W, Parikh AA, Stoeltzing O, Jung YD, Bucana CD, Radinsky R, Gallick GE, Ellis LM. Source: Lab Invest. 2002 October; 82(10): 1377-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379772&dopt=Abstract
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Impaired expression of proteasome subunits and human leukocyte antigens class I in human colon cancer cells. Author(s): Miyagi T, Tatsumi T, Takehara T, Kanto T, Kuzushita N, Sugimoto Y, Jinushi M, Kasahara A, Sasaki Y, Hori M, Hayashi N. Source: J Gastroenterol Hepatol. 2003 January; 18(1): 32-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519221&dopt=Abstract
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Improved response of colon cancer xenografts to radioimmunotherapy with pentoxifylline treatment. Author(s): Kinuya S, Yokoyama K, Konishi S, Li XF, Watanabe N, Shuke N, Takayama T, Bunko H, Michigishi T, Tonami N. Source: Eur J Nucl Med. 2001 June; 28(6): 750-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11440036&dopt=Abstract
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Improvement of carcinoembryonic antigen-specific prodrug gene therapy for experimental colon cancer. Author(s): Ueda K, Iwahashi M, Nakamori M, Nakamura M, Matsuura I, Ojima T, Yamaue H. Source: Surgery. 2003 March; 133(3): 309-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660644&dopt=Abstract
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In situ cancer vaccination with a replication-conditional HSV for the treatment of liver metastasis of colon cancer. Author(s): Endo T, Toda M, Watanabe M, Iizuka Y, Kubota T, Kitajima M, Kawakami Y. Source: Cancer Gene Ther. 2002 February; 9(2): 142-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11857031&dopt=Abstract
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In vitro and in vivo characteristics of a human colon cancer cell line, SNU-C5N, expressing sodium-iodide symporter. Author(s): Min JJ, Chung JK, Lee YJ, Shin JH, Yeo JS, Jeong JM, Lee DS, Bom HS, Lee MC. Source: Nucl Med Biol. 2002 July; 29(5): 537-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088723&dopt=Abstract
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In vitro and in vivo treatment of colon cancer by VIP antagonists. Author(s): Levy A, Gal R, Granoth R, Dreznik Z, Fridkin M, Gozes I. Source: Regul Pept. 2002 November 15; 109(1-3): 127-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409224&dopt=Abstract
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In vivo gene therapy for colon cancer using adenovirus-mediated, transfer of the fusion gene cytosine deaminase and uracil phosphoribosyltransferase. Author(s): Chung-Faye GA, Chen MJ, Green NK, Burton A, Anderson D, Mautner V, Searle PF, Kerr DJ. Source: Gene Ther. 2001 October; 8(20): 1547-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704815&dopt=Abstract
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In vivo imaging of human colon cancer xenografts in immunodeficient mice using a guanylyl cyclase C--specific ligand. Author(s): Wolfe HR, Mendizabal M, Lleong E, Cuthbertson A, Desai V, Pullan S, Fujii DK, Morrison M, Pither R, Waldman SA. Source: J Nucl Med. 2002 March; 43(3): 392-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11884500&dopt=Abstract
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Incidental detection of colon cancer by FDG positron emission tomography in patients examined for pulmonary nodules. Author(s): Zhuang H, Hickeson M, Chacko TK, Duarte PS, Nakhoda KZ, Feng Q, Alavi A. Source: Clin Nucl Med. 2002 September; 27(9): 628-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192279&dopt=Abstract
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Increase in ceramide level alters the lysosomal targeting of cathepsin D prior to onset of apoptosis in HT-29 colon cancer cells. Author(s): De Stefanis D, Reffo P, Bonelli G, Baccino FM, Sala G, Ghidoni R, Codogno P, Isidoro C. Source: Biol Chem. 2002 June; 383(6): 989-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222689&dopt=Abstract
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Increased expression of CD40 ligand on activated T cells of patients with colon cancer. Author(s): Buning C, Kruger K, Sieber T, Schoeler D, Schriever F. Source: Clin Cancer Res. 2002 April; 8(4): 1147-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11948126&dopt=Abstract
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Increased expression of UDP-galactose transporter messenger RNA in human colon cancer tissues and its implication in synthesis of Thomsen-Friedenreich antigen and sialyl Lewis A/X determinants. Author(s): Kumamoto K, Goto Y, Sekikawa K, Takenoshita S, Ishida N, Kawakita M, Kannagi R. Source: Cancer Res. 2001 June 1; 61(11): 4620-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11389099&dopt=Abstract
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Increased frequency of colon polyps leading to colon cancer among women. Author(s): Burger-Weiser G, Waterhouse L, Richter S, Kitchen CM. Source: Arch Med Res. 2003 March-April; 34(2): 152-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700014&dopt=Abstract
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Increased membrane type 1 matrix metalloproteinase expression from adenoma to colon cancer: a possible mechanism of neoplastic progression. Author(s): Malhotra S, Newman E, Eisenberg D, Scholes J, Wieczorek R, Mignatti P, Shamamian P. Source: Dis Colon Rectum. 2002 April; 45(4): 537-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006939&dopt=Abstract
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Increased Src activity disrupts cadherin/catenin-mediated homotypic adhesion in human colon cancer and transformed rodent cells. Author(s): Irby RB, Yeatman TJ. Source: Cancer Res. 2002 May 1; 62(9): 2669-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980666&dopt=Abstract
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Increasing the intra-Golgi pH of cultured LS174T goblet-differentiated cells mimics the decreased mucin sulfation and increased Thomsen-Friedenreich antigen (Gal beta1-3GalNac alpha-) expression seen in colon cancer. Author(s): Campbell BJ, Rowe GE, Leiper K, Rhodes JM. Source: Glycobiology. 2001 May; 11(5): 385-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11425799&dopt=Abstract
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Induction of apoptosis by 1,4-phenylenebis(methylene)selenocyanate in cultured human colon cancer cells. Author(s): Lee SK, Heo YH, Steele VE, Pezzuto JM. Source: Anticancer Res. 2002 January-February; 22(1A): 97-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12017340&dopt=Abstract
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Induction of cyclooxygenase-2 in monocyte/macrophage by mucins secreted from colon cancer cells. Author(s): Inaba T, Sano H, Kawahito Y, Hla T, Akita K, Toda M, Yamashina I, Inoue M, Nakada H. Source: Proc Natl Acad Sci U S A. 2003 March 4; 100(5): 2736-41. Epub 2003 February 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598658&dopt=Abstract
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Induction of multidrug resistance proteins MRP1 and MRP3 and gammaglutamylcysteine synthetase gene expression by nonsteroidal anti-inflammatory drugs in human colon cancer cells. Author(s): Tatebe S, Sinicrope FA, Kuo MT. Source: Biochem Biophys Res Commun. 2002 February 8; 290(5): 1427-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11820781&dopt=Abstract
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Induction of resistance to the multitargeted antifolate Pemetrexed (ALIMTA) in WiDr human colon cancer cells is associated with thymidylate synthase overexpression. Author(s): Sigmond J, Backus HH, Wouters D, Temmink OH, Jansen G, Peters GJ. Source: Biochem Pharmacol. 2003 August 1; 66(3): 431-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907242&dopt=Abstract
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Influence of the nitric oxide donor glyceryl trinitrate on apoptotic pathways in human colon cancer cells. Author(s): Millet A, Bettaieb A, Renaud F, Prevotat L, Hammann A, Solary E, Mignotte B, Jeannin JF. Source: Gastroenterology. 2002 July; 123(1): 235-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105852&dopt=Abstract
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Inguinal hernia is not a sign of colon cancer: results of a prospective screening trial. Author(s): Avidan B, Sonnenberg A, Bhatia H, Aranha G, Schnell TG, Sontag SJ. Source: Aliment Pharmacol Ther. 2002 June; 16(6): 1197-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030963&dopt=Abstract
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Inhibition of endogenous carcinoembryonic antigen (CEA) increases the apoptotic rate of colon cancer cells and inhibits metastatic tumor growth. Author(s): Wirth T, Soeth E, Czubayko F, Juhl H. Source: Clin Exp Metastasis. 2002; 19(2): 155-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11964079&dopt=Abstract
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Inhibition of human colon cancer cell growth by antisense oligodeoxynucleotides targeted at basic fibroblast growth factor. Author(s): Netzer P, Domek M, Pai R, Halter F, Tarnawski A. Source: Aliment Pharmacol Ther. 2001 October; 15(10): 1673-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11564009&dopt=Abstract
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Inhibition of protein farnesylation enhances the chemotherapeutic efficacy of the novel geranylgeranyltransferase inhibitor BAL9611 in human colon cancer cells. Author(s): Di Paolo A, Danesi R, Caputo S, Macchia M, Lastella M, Boggi U, Mosca F, Marchetti A, Del Tacca M. Source: Br J Cancer. 2001 June 1; 84(11): 1535-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11384105&dopt=Abstract
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Inhibitory effect of a selective cyclooxygenase-2 inhibitor on liver metastasis of colon cancer. Author(s): Nagatsuka I, Yamada N, Shimizu S, Ohira M, Nishino H, Seki S, Hirakawa K. Source: Int J Cancer. 2002 August 10; 100(5): 515-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124799&dopt=Abstract
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Initiation of human colon cancer cell proliferation by trypsin acting at proteaseactivated receptor-2. Author(s): Darmoul D, Marie JC, Devaud H, Gratio V, Laburthe M. Source: Br J Cancer. 2001 September 1; 85(5): 772-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11531266&dopt=Abstract
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Insights into genetic testing for colon cancer: the nurse practitioner role. Author(s): Burrer CV, Bauer SM. Source: Clin Excell Nurse Pract. 2000 November; 4(6): 349-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11858318&dopt=Abstract
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Insulin, insulin-like growth factors and colon cancer: a review of the evidence. Author(s): Giovannucci E. Source: J Nutr. 2001 November; 131(11 Suppl): 3109S-20S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694656&dopt=Abstract
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Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells. Author(s): Fukuda R, Hirota K, Fan F, Jung YD, Ellis LM, Semenza GL. Source: J Biol Chem. 2002 October 11; 277(41): 38205-11. Epub 2002 July 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149254&dopt=Abstract
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Insulin-like growth factor 1 receptor activates c-SRC and modifies transformation and motility of colon cancer in vitro. Author(s): Sekharam M, Nasir A, Kaiser HE, Coppola D. Source: Anticancer Res. 2003 March-April; 23(2B): 1517-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820418&dopt=Abstract
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Insulin-like growth factor-II renders LIM 2405 human colon cancer cells resistant to butyrate-induced apoptosis: a potential mechanism for colon cancer cell survival in vivo. Author(s): Leng SL, Leeding KS, Gibson PR, Bach LA. Source: Carcinogenesis. 2001 October; 22(10): 1625-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11577001&dopt=Abstract
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Integrin alpha(v)beta6-associated ERK2 mediates MMP-9 secretion in colon cancer cells. Author(s): Gu X, Niu J, Dorahy DJ, Scott R, Agrez MV. Source: Br J Cancer. 2002 July 29; 87(3): 348-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12177807&dopt=Abstract
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Integrin alpha2 and extracellular signal-regulated kinase are functionally linked in highly malignant autocrine transforming growth factor-alpha-driven colon cancer cells. Author(s): Sawhney RS, Sharma B, Humphrey LE, Brattain MG. Source: J Biol Chem. 2003 May 30; 278(22): 19861-9. Epub 2003 March 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657625&dopt=Abstract
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Integrin alpha3 expression as a prognostic factor in colon cancer: association with MRP-1/CD9 and KAI1/CD82. Author(s): Hashida H, Takabayashi A, Tokuhara T, Taki T, Kondo K, Kohno N, Yamaoka Y, Miyake M. Source: Int J Cancer. 2002 February 1; 97(4): 518-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11802216&dopt=Abstract
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Integrin expression in colon cancer cells is regulated by the cytoplasmic domain of the beta6 integrin subunit. Author(s): Niu J, Dorahy DJ, Gu X, Scott RJ, Draganic B, Ahmed N, Agrez MV. Source: Int J Cancer. 2002 June 1; 99(4): 529-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992542&dopt=Abstract
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Intercellular junctions, apical differentiation, and infiltrative features in colon cancer: an ultrastructural study. The Colon Cancer Team at IMAS. Author(s): Lloreta-Trull J, Munne A, Marinoso ML, Ferrer MD, Serrano S; Hospital del Mar-IMAS-IMIM. Source: Ultrastruct Pathol. 2001 July-August; 25(4): 289-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11577773&dopt=Abstract
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Intestinal bacterial beta-glucuronidase activity of patients with colon cancer. Author(s): Kim DH, Jin YH. Source: Arch Pharm Res. 2001 December; 24(6): 564-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11794536&dopt=Abstract
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Intraoperative radiation therapy for patients with recurrent rectal and sigmoid colon cancer in previously irradiated fields. Author(s): Pezner RD, Chu DZ, Ellenhorn JD. Source: Radiother Oncol. 2002 July; 64(1): 47-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208575&dopt=Abstract
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Intraoperative radiochromoguided mapping of sentinel lymph node in colon cancer. Author(s): Nastro P, Sodo M, Dodaro CA, Gargiulo S, Acampa W, Bracale U, Renda A. Source: Tumori. 2002 July-August; 88(4): 352-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400991&dopt=Abstract
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Intraoperative sentinel lymph node mapping in patients with colon cancer. Author(s): Paramo JC, Summerall J, Wilson C, Cabral A, Willis I, Wodnicki H, Poppiti R, Mesko TW. Source: Am J Surg. 2001 July; 182(1): 40-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11532413&dopt=Abstract
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Investigation of the prognostic and predictive value of thymidylate synthase, p53, and Ki-67 in patients with locally advanced colon cancer. Author(s): Allegra CJ, Parr AL, Wold LE, Mahoney MR, Sargent DJ, Johnston P, Klein P, Behan K, O'Connell MJ, Levitt R, Kugler JW, Tria Tirona M, Goldberg RM. Source: J Clin Oncol. 2002 April 1; 20(7): 1735-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11919229&dopt=Abstract
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Involvement of both extracellular signal-regulated kinase and c-jun N-terminal kinase pathways in the 12-O-tetradecanoylphorbol-13-acetate-induced upregulation of p21(Cip1) in colon cancer cells. Author(s): Lin SY, Liang YC, Ho YS, Tsai SH, Pan S, Lee WS. Source: Mol Carcinog. 2002 September; 35(1): 21-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12203364&dopt=Abstract
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Is an FDG-PET scan the new imaging standard for colon cancer? Author(s): Swanson RS. Source: Ann Surg Oncol. 2001 December; 8(10): 752-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11776485&dopt=Abstract
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Is development of bronchial metastasis following laparoscopic right hemicolectomy for colon cancer related to pneumoperitoneum? Author(s): Goletti O, Battini A, Zocco G, Cavina E. Source: Surg Endosc. 2003 January; 17(1): 168. Epub 2002 October 08. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571744&dopt=Abstract
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Isolated metastatic adrenal involvement with colon cancer and FDG coincidence detection imaging. Author(s): Des Guetz G, Montravers F, Spatzierer, Tabah I, Grahek D, Talbot JN, Bouillot JL, Pujade-Lauraine E. Source: Clin Nucl Med. 2003 March; 28(3): 238. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592139&dopt=Abstract
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Isolated splenic metastasis of sigmoid colon cancer: a case report. Author(s): Okuyama T, Oya M, Ishikawa H. Source: Jpn J Clin Oncol. 2001 July; 31(7): 341-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11518749&dopt=Abstract
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Isolation and sequencing of a novel tropomyosin isoform preferentially associated with colon cancer. Author(s): Lin JL, Geng X, Bhattacharya SD, Yu JR, Reiter RS, Sastri B, Glazier KD, Mirza ZK, Wang KK, Amenta PS, Das KM, Lin JJ. Source: Gastroenterology. 2002 July; 123(1): 152-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105844&dopt=Abstract
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Isolation of a novel member of small G protein superfamily and its expression in colon cancer. Author(s): Yan W, Wang WL, Zhu F, Chen SQ, Li QL, Wang L. Source: World J Gastroenterol. 2003 August; 9(8): 1719-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918107&dopt=Abstract
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Isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis, induces cell cycle arrest and apoptosis in human colon cancer cells. Author(s): Frederich M, Bentires-Alj M, Tits M, Angenot L, Greimers R, Gielen J, Bours V, Merville MP. Source: J Pharmacol Exp Ther. 2003 March; 304(3): 1103-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604687&dopt=Abstract
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JAMA patient page. Colon cancer screening. Author(s): Torpy JM, Lynm C, Glass RM. Source: Jama. 2003 March 12; 289(10): 1334. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633198&dopt=Abstract
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JMV1155: a novel inhibitor of glycine-extended progastrin-mediated growth of a human colon cancer in vivo. Author(s): Litvak DA, Hellmich MR, Iwase K, Evers BM, Martinez J, Amblard M, Townsend CM Jr. Source: Anticancer Res. 1999 January-February; 19(1A): 45-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10226523&dopt=Abstract
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Katie's crusade. Colon cancer is one of the deadliest and most preventable malignancies. What you need to know about the disease--and the surprisingly painless test that could save your life. Author(s): Gorman C. Source: Time. 2000 March 13; 155(10): 70-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11009699&dopt=Abstract
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Kill and cure: dietary augmentation of immune defences against colon cancer. Author(s): Armstrong F, Mathers JC. Source: Proc Nutr Soc. 2000 May; 59(2): 215-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10946790&dopt=Abstract
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Lack of colon cancer coverage in seven women's magazines. Author(s): Gerlach KK, Marino C, Weed DL, Hoffman-Goetz L. Source: Women Health. 1997; 26(2): 57-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9472955&dopt=Abstract
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Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. Phoenix Colon Cancer Prevention Physicians' Network. Author(s): Alberts DS, Martinez ME, Roe DJ, Guillen-Rodriguez JM, Marshall JR, van Leeuwen JB, Reid ME, Ritenbaugh C, Vargas PA, Bhattacharyya AB, Earnest DL, Sampliner RE. Source: N Engl J Med. 2000 April 20; 342(16): 1156-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10770980&dopt=Abstract
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Laminin mediates tethering and spreading of colon cancer cells in physiological shear flow. Author(s): Kitayama J, Nagawa H, Tsuno N, Osada T, Hatano K, Sunami E, Saito H, Muto T. Source: Br J Cancer. 1999 August; 80(12): 1927-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10471041&dopt=Abstract
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Lanreotide-induced modulation of 5-fluorouracil or mitomycin C cytotoxicity in human colon cancer cell lines: a preclinical study. Author(s): Tesei A, Ricotti L, De Paola F, Casini-Raggi C, Barzanti F, Frassineti GL, Zoli W. Source: J Chemother. 2000 October; 12(5): 421-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11128563&dopt=Abstract
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Laparoscopic approach to colon cancer. Author(s): Tisminezky B, Nelson H. Source: Adv Surg. 2000; 34: 67-119. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997216&dopt=Abstract
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Laparoscopic colectomy for colon cancer: trial update. Author(s): Stocchi L, Nelson H. Source: J Surg Oncol. 1998 August; 68(4): 255-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9721713&dopt=Abstract
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Laparoscopic colectomy for colon cancer--a trial update. Author(s): Nelson H. Source: Swiss Surg. 2001; 7(6): 248-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771442&dopt=Abstract
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Laparoscopic colectomy for Dukes A colon cancer. Author(s): Kakisako K, Sato K, Adachi Y, Shiraishi N, Miyahara M, Kitano S. Source: Surg Laparosc Endosc Percutan Tech. 2000 April; 10(2): 66-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10789575&dopt=Abstract
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Laparoscopic right hemicolectomy with radical lymph node dissection using the notouch isolation technique for advanced colon cancer. Author(s): Fujita J, Uyama I, Sugioka A, Komori Y, Matsui H, Hasumi A. Source: Surg Today. 2001; 31(1): 93-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11213054&dopt=Abstract
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Laparoscopic surgery for stage III colon cancer: long-term follow-up. Author(s): Franklin ME, Kazantsev GB, Abrego D, Diaz-E JA, Balli J, Glass JL. Source: Surg Endosc. 2000 July; 14(7): 612-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10948295&dopt=Abstract
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Laparoscopic vs open hemicolectomy for colon cancer. Author(s): Lezoche E, Feliciotti F, Paganini AM, Guerrieri M, De Sanctis A, Minervini S, Campagnacci R. Source: Surg Endosc. 2002 April; 16(4): 596-602. Epub 2002 January 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11972196&dopt=Abstract
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Laparoscopic-assisted surgery for colon cancer. Author(s): Urbach DR. Source: Jama. 2002 April 17; 287(15): 1938; Author Reply 1939. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11960530&dopt=Abstract
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Laparoscopic-assisted surgery for colon cancer. Author(s): Marescaux J, Rubino F, Leroy J, Henri M. Source: Jama. 2002 April 17; 287(15): 1938-9; Author Reply 1939. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11960531&dopt=Abstract
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Laparoscopy for colon cancer. Author(s): Rickard MJ, Bokey EL. Source: Surg Oncol Clin N Am. 2001 July; 10(3): 579-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11685929&dopt=Abstract
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Laparoscopy-assisted colectomy versus open colectomy for treatment of nonmetastatic colon cancer: a randomised trial. Author(s): Lacy AM, Garcia-Valdecasas JC, Delgado S, Castells A, Taura P, Pique JM, Visa J. Source: Lancet. 2002 June 29; 359(9325): 2224-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12103285&dopt=Abstract
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Late onset and high incidence of colon cancer of the mutator phenotype with hypermethylated hMLH1 gene in women. Author(s): Malkhosyan SR, Yamamoto H, Piao Z, Perucho M. Source: Gastroenterology. 2000 August; 119(2): 598. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10960275&dopt=Abstract
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Lectins, colitis and colon cancer. Author(s): Rhodes JM. Source: J R Coll Physicians Lond. 2000 March-April; 34(2): 191-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10816877&dopt=Abstract
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Left ventricular function in colon cancer patients receiving adjuvant fluoro-folate chemotherapy: an echocardiographic study. Author(s): Balloni L, Porta C, Rossi S, Gola A, Pugliese P, Ferrari S, Bovio A, Danova M, Riccardi A. Source: Oncol Rep. 2000 July-August; 7(4): 887-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10854564&dopt=Abstract
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Less cytotoxicity to combination therapy of 5-fluorouracil and cisplatin than 5fluorouracil alone in human colon cancer cell lines. Author(s): Chen XX, Lai MD, Zhang YL, Huang Q. Source: World J Gastroenterol. 2002 October; 8(5): 841-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378627&dopt=Abstract
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Leukocyte recruitment in colon cancer: role of cell adhesion molecules, nitric oxide, and transforming growth factor beta1. Author(s): Bessa X, Elizalde JI, Mitjans F, Pinol V, Miquel R, Panes J, Piulats J, Pique JM, Castells A. Source: Gastroenterology. 2002 April; 122(4): 1122-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910362&dopt=Abstract
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Levels of E2F-1 expression are higher in lung metastasis of colon cancer as compared with hepatic metastasis and correlate with levels of thymidylate synthase. Author(s): Banerjee D, Gorlick R, Liefshitz A, Danenberg K, Danenberg PC, Danenberg PV, Klimstra D, Jhanwar S, Cordon-Cardo C, Fong Y, Kemeny N, Bertino JR. Source: Cancer Res. 2000 May 1; 60(9): 2365-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10811110&dopt=Abstract
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Lifestyle and colon cancer: an assessment of factors associated with risk. Author(s): Slattery ML, Edwards SL, Boucher KM, Anderson K, Caan BJ. Source: Am J Epidemiol. 1999 October 15; 150(8): 869-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10522658&dopt=Abstract
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Lifestyle factors and Ki-ras mutations in colon cancer tumors. Author(s): Slattery ML, Anderson K, Curtin K, Ma K, Schaffer D, Edwards S, Samowitz W. Source: Mutat Res. 2001 November 1; 483(1-2): 73-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11600135&dopt=Abstract
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Liganded VDR induces CYP3A4 in small intestinal and colon cancer cells via DR3 and ER6 vitamin D responsive elements. Author(s): Thompson PD, Jurutka PW, Whitfield GK, Myskowski SM, Eichhorst KR, Dominguez CE, Haussler CA, Haussler MR. Source: Biochem Biophys Res Commun. 2002 December 20; 299(5): 730-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12470639&dopt=Abstract
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Limited effect of consumption of uncooked (RS2) or retrograded (RS3) resistant starch on putative risk factors for colon cancer in healthy men. Author(s): Heijnen ML, van Amelsvoort JM, Deurenberg P, Beynen AC. Source: Am J Clin Nutr. 1998 February; 67(2): 322-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9459382&dopt=Abstract
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Lithocholic acid and sulphated lithocholic acid differ in the ability to promote matrix metalloproteinase secretion in the human colon cancer cell line CaCo-2. Author(s): Halvorsen B, Staff AC, Ligaarden S, Prydz K, Kolset SO. Source: Biochem J. 2000 July 1; 349(Pt 1): 189-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10861227&dopt=Abstract
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Littoral cell angioma associated with portal hypertension and resected colon cancer. Author(s): Steensma DP, Morice WG. Source: Acta Haematol. 2000; 104(2-3): 131-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11154990&dopt=Abstract
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Liver colonization by human colon cancer cells is reduced by antisense inhibition of MUC2 mucin synthesis. Author(s): Sternberg LR, Byrd JC, Yunker CK, Dudas S, Hoon VK, Bresalier RS. Source: Gastroenterology. 1999 February; 116(2): 363-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9922317&dopt=Abstract
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Liver metastasis and adhesion to the sinusoidal endothelium by human colon cancer cells is related to mucin carbohydrate chain length. Author(s): Bresalier RS, Byrd JC, Brodt P, Ogata S, Itzkowitz SH, Yunker CK. Source: Int J Cancer. 1998 May 18; 76(4): 556-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9590134&dopt=Abstract
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Long tube for obstructing left-sided colon cancer. Author(s): Adachi Y, Okita K, Nozoe T, Iso Y, Yoh R, Matsumata T. Source: Dig Surg. 1999; 16(3): 178-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10436363&dopt=Abstract
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Long-term diuretic therapy in patients with coronary disease: increased colon cancerrelated mortality over a 5-year follow-up. Author(s): Tenenbaum A, Grossman E, Fisman EZ, Adler Y, Boyko V, Jonas M, Behar S, Motro M, Reicher-Reiss H. Source: J Hum Hypertens. 2001 June; 15(6): 373-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11439311&dopt=Abstract
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Long-term prognosis for colon cancer related to consistent radical surgery: multivariate analysis of clinical, surgical, and pathologic variables. Author(s): Jagoditsch M, Lisborg PH, Jatzko GR, Wette V, Kropfitsch G, Denk H, Klimpfinger M, Stettner HM. Source: World J Surg. 2000 October; 24(10): 1264-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11071473&dopt=Abstract
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Long-term prognostic value of positive peritoneal washing in colon cancer. Author(s): Wind P, Norklinger B, Roger V, Kahlil A, Guin E, Parc R. Source: Scand J Gastroenterol. 1999 June; 34(6): 606-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10440611&dopt=Abstract
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Long-term survival after immunochemotherapy for juvenile colon cancer with peritoneal dissemination: a case report. Author(s): Mukai M, Tokunaga N, Yasuda S, Mukohyama S, Kameya T, Ishikawa K, Iwase H, Suzuki T, Ishida H, Sadahiro S, Makuuchi H. Source: Oncol Rep. 2000 November-December; 7(6): 1343-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11032941&dopt=Abstract
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Loss of epithelial differentiation markers and acquisition of vimentin expression after xenograft with laminin-1 enhance migratory and invasive abilities of human colon cancer cells LoVo C5. Author(s): Dumortier J, Daemi N, Pourreyron C, Anderson W, Bellaton C, Jacquier MF, Bertrand S, Chayvialle JA, Remy L. Source: Differentiation. 1998 July; 63(3): 141-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9697308&dopt=Abstract
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Loss of heterozygosity in the region including the BRCA1 gene on 17q in colon cancer. Author(s): Garcia-Patino E, Gomendio B, Lleonart M, Silva JM, Garcia JM, Provencio M, Cubedo R, Espana P, Ramon y Cajal S, Bonilla F. Source: Cancer Genet Cytogenet. 1998 July 15; 104(2): 119-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9666805&dopt=Abstract
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Loss of heterozygosity of APC and DCC tumor suppressor genes in human sporadic colon cancer. Author(s): Sturlan S, Kapitanovic S, Kovacevic D, Lukac J, Spaventi S, Spaventi R, Pavelic K. Source: J Mol Med. 1999 March; 77(3): 316-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10090594&dopt=Abstract
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Loss of heterozygosity of DPC4 tumor suppressor gene in human sporadic colon cancer. Author(s): Had ija MP, Kapitanovic S, Radosevic S, Cacev T, Mirt M, Kovacevic D, Cacev T, Hadzija M, Spaventi R, Pavelic K. Source: J Mol Med. 2001 April; 79(2-3): 128-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11357936&dopt=Abstract
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Loss of immunohistochemical E-cadherin expression in colon cancer is not due to structural gene alterations. Author(s): Schuhmacher C, Becker I, Oswald S, Atkinson MJ, Nekarda H, Becker KF, Mueller J, Siewert JR, Hofler H. Source: Virchows Arch. 1999 June; 434(6): 489-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10394882&dopt=Abstract
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Loss-of-function mutations in PPAR gamma associated with human colon cancer. Author(s): Sarraf P, Mueller E, Smith WM, Wright HM, Kum JB, Aaltonen LA, de la Chapelle A, Spiegelman BM, Eng C. Source: Mol Cell. 1999 June; 3(6): 799-804. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10394368&dopt=Abstract
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Lovastatin augments apoptosis induced by chemotherapeutic agents in colon cancer cells. Author(s): Feleszko W, Jakobisiak M. Source: Clin Cancer Res. 2000 March; 6(3): 1198-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10741752&dopt=Abstract
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Lovastatin augments apoptosis induced by chemotherapeutic agents in colon cancer cells. Author(s): Agarwal B, Bhendwal S, Halmos B, Moss SF, Ramey WG, Holt PR. Source: Clin Cancer Res. 1999 August; 5(8): 2223-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10473109&dopt=Abstract
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Low serum leptin level in colon cancer patients without significant weight loss. Author(s): Arpaci F, Yilmaz MI, Ozet A, Ayta H, Ozturk B, Komurcu S, Ozata M. Source: Tumori. 2002 March-April; 88(2): 147-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088256&dopt=Abstract
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Low-dose deoxycholic acid stimulates putrescine uptake in colon cancer cells (Caco2). Author(s): Milovic V, Stein J, Odera G, Gilani S, Murphy GM. Source: Cancer Lett. 2000 June 30; 154(2): 195-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10806308&dopt=Abstract
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Lymph node micrometastases do not predict relapse in stage II colon cancer. Author(s): Tschmelitsch J, Klimstra DS, Cohen AM. Source: Ann Surg Oncol. 2000 September; 7(8): 601-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11005559&dopt=Abstract
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Lymph node size and metastatic infiltration in colon cancer. Author(s): Monig SP, Baldus SE, Zirbes TK, Schroder W, Lindemann DG, Dienes HP, Holscher AH. Source: Ann Surg Oncol. 1999 September; 6(6): 579-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10493627&dopt=Abstract
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Lymphatic mapping of nodal micrometastasis in colon cancer: putting the cart before the horse? Author(s): Bilchik AJ, Nora DT. Source: Ann Surg Oncol. 2002 July; 9(6): 529-31. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12095966&dopt=Abstract
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Lymphocyte labile iron pool, plasma iron, transferrin saturation and ferritin levels in colon cancer patients. Author(s): Gackowski D, Kruszewsk M, Banaszkiewicz Z, Jawien A, Olinski R. Source: Acta Biochim Pol. 2002; 49(1): 269-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12136950&dopt=Abstract
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Mad-1 is the exclusive JC virus strain present in the human colon, and its transcriptional control region has a deleted 98-base-pair sequence in colon cancer tissues. Author(s): Ricciardiello L, Chang DK, Laghi L, Goel A, Chang CL, Boland CR. Source: J Virol. 2001 February; 75(4): 1996-2001. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11160700&dopt=Abstract
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Major campaign to raise colon cancer awareness in Germany. Author(s): Habeck M. Source: Lancet Oncol. 2001 June; 2(6): 328. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11905744&dopt=Abstract
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Manifestation of bilateral huge ovarian metastases from colon cancer immediately after the initial operation: report of a case. Author(s): Sakakura C, Hagiwara A, Kato D, Hamada T, Yamagishi H. Source: Surg Today. 2002; 32(4): 371-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027206&dopt=Abstract
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Markers of drug resistance in relapsing colon cancer. Author(s): Lazaris AC, Kavantzas NG, Zorzos HS, Tsavaris NV, Davaris PS. Source: J Cancer Res Clin Oncol. 2002 February; 128(2): 114-8. Epub 2001 November 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11862483&dopt=Abstract
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Meat intake, heterocyclic amines, and colon cancer. Author(s): Maric RN, Cheng KK. Source: Am J Gastroenterol. 2000 December; 95(12): 3683-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11151942&dopt=Abstract
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Mechanism of colon cancer cell apoptosis mediated by pyropheophorbide-a methylester photosensitization. Author(s): Matroule JY, Carthy CM, Granville DJ, Jolois O, Hunt DW, Piette J. Source: Oncogene. 2001 July 5; 20(30): 4070-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11494135&dopt=Abstract
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Mechanisms involved in development of resistance to adenovirus-mediated proapoptotic gene therapy in DLD1 human colon cancer cell line. Author(s): Zhang L, Gu J, Lin T, Huang X, Roth JA, Fang B. Source: Gene Ther. 2002 September; 9(18): 1262-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215894&dopt=Abstract
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Medicolegal implications of colon cancer screening. Author(s): Feld AD. Source: Gastrointest Endosc Clin N Am. 2002 January; 12(1): 171-9, Viii-Ix. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11916158&dopt=Abstract
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Met receptor overexpression and oncogenic Ki-ras mutation cooperate to enhance tumorigenicity of colon cancer cells in vivo. Author(s): Long IS, Han K, Li M, Shirasawa S, Sasazuki T, Johnston M, Tsao MS. Source: Mol Cancer Res. 2003 March; 1(5): 393-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651912&dopt=Abstract
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Metastatic breast carcinoma masquerading as primary colon cancer. Author(s): Yokota T, Kunii Y, Kagami M, Yamada Y, Takahashi M, Kikuchi S, Nakamura M, Yamauchi H. Source: Am J Gastroenterol. 2000 October; 95(10): 3014-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11051411&dopt=Abstract
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Methoxyamine potentiates DNA single strand breaks and double strand breaks induced by temozolomide in colon cancer cells. Author(s): Taverna P, Liu L, Hwang HS, Hanson AJ, Kinsella TJ, Gerson SL. Source: Mutat Res. 2001 May 10; 485(4): 269-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11585361&dopt=Abstract
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Methylation of CpG loci in 5'-flanking region alters steady-state expression of adenomatous polyposis coli gene in colon cancer cell lines. Author(s): Sakamoto Y, Kitazawa R, Maeda S, Kitazawa S. Source: J Cell Biochem. 2001; 80(3): 415-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11135372&dopt=Abstract
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Methylation silencing and mutations of the p14ARF and p16INK4a genes in colon cancer. Author(s): Burri N, Shaw P, Bouzourene H, Sordat I, Sordat B, Gillet M, Schorderet D, Bosman FT, Chaubert P. Source: Lab Invest. 2001 February; 81(3): 217-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11233970&dopt=Abstract
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Methylation silencing and mutations of the p14ARF and p16INK4a genes in colon cancer. Author(s): Burri N, Shaw P, Bouzourene H, Sordat I, Sordat B, Gillet M, Schorderet D, Bosman FT, Chaubert P. Source: Lab Invest. 2001 February; 81(2): 217-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11232644&dopt=Abstract
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Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis. Author(s): Kiesslich R, Fritsch J, Holtmann M, Koehler HH, Stolte M, Kanzler S, Nafe B, Jung M, Galle PR, Neurath MF. Source: Gastroenterology. 2003 April; 124(4): 880-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671882&dopt=Abstract
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Methylenetetrahydrofolate reductase 677 C-->T polymorphism and risk of proximal colon cancer in north Italy. Author(s): Toffoli G, Gafa R, Russo A, Lanza G, Dolcetti R, Sartor F, Libra M, Viel A, Boiocchi M. Source: Clin Cancer Res. 2003 February; 9(2): 743-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576444&dopt=Abstract
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Methylxanthine sensitization of human colon cancer cells to 186Re-labeled monoclonal antibody. Author(s): Kinuya S, Yokoyama K, Kudo M, Kasahara Y, Kobayashi K, Motoishi S, Onoma K, Bunko H, Michigishi T, Tonami N. Source: J Nucl Med. 2001 April; 42(4): 596-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11337548&dopt=Abstract
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Microsatellite instability and high content of activated cytotoxic lymphocytes identify colon cancer patients with a favorable prognosis. Author(s): Guidoboni M, Gafa R, Viel A, Doglioni C, Russo A, Santini A, Del Tin L, Macri E, Lanza G, Boiocchi M, Dolcetti R. Source: Am J Pathol. 2001 July; 159(1): 297-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11438476&dopt=Abstract
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Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level. Author(s): Samowitz WS, Curtin K, Ma KN, Schaffer D, Coleman LW, Leppert M, Slattery ML. Source: Cancer Epidemiol Biomarkers Prev. 2001 September; 10(9): 917-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11535541&dopt=Abstract
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Minilaparotomy approach to colon cancer. Author(s): Takegami K, Kawaguchi Y, Nakayama H, Kubota Y, Nagawa H. Source: Surg Today. 2003; 33(6): 414-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768366&dopt=Abstract
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Minimal liver resection strongly stimulates the growth of human colon cancer in the liver of nude mice. Author(s): Rashidi B, An Z, Sun FX, Sasson A, Gamagammi R, Moossa AR, Hoffman RM. Source: Clin Exp Metastasis. 1999; 17(6): 497-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10763915&dopt=Abstract
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Minute depressed colon cancer with submucosal invasion. Author(s): Shima H, Tanaka S, Kuwai T, Hiyama T, Kitadai Y, Sumii M, Yoshihara M, Haruma K, Chayama K. Source: Gastrointest Endosc. 2003 April; 57(4): 564-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665772&dopt=Abstract
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Mirk protein kinase is a mitogen-activated protein kinase substrate that mediates survival of colon cancer cells. Author(s): Lee K, Deng X, Friedman E. Source: Cancer Res. 2000 July 1; 60(13): 3631-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10910078&dopt=Abstract
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Modeling of genetic instability--looking for "Newton's binomial" of colon cancer. Author(s): da Costa LT. Source: Cancer Biol Ther. 2002 November-December; 1(6): 693-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739541&dopt=Abstract
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Modelling time-dependent hazard ratios in relative survival: application to colon cancer. Author(s): Bolard P, Quantin C, Esteve J, Faivre J, Abrahamowicz M. Source: J Clin Epidemiol. 2001 October; 54(10): 986-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11576809&dopt=Abstract
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Modifiable risk factors for colon cancer. Author(s): Giovannucci E. Source: Gastroenterol Clin North Am. 2002 December; 31(4): 925-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12489270&dopt=Abstract
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Modulation by colony stimulating factors of human epithelial colon cancer cell apoptosis. Author(s): Calatayud S, Warner TD, Breese EJ, Mitchell JA. Source: Cytokine. 2002 November 24; 20(4): 163-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12543080&dopt=Abstract
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Modulation of angiogenesis-related proteins synthesis by sodium butyrate in colon cancer cell line HT29. Author(s): Pellizzaro C, Coradini D, Daidone MG. Source: Carcinogenesis. 2002 May; 23(5): 735-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12016145&dopt=Abstract
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Modulation of colony stimulating factor release and apoptosis in human colon cancer cells by anticancer drugs. Author(s): Calatayud S, Warner TD, Mitchell JA. Source: Br J Cancer. 2002 April 22; 86(8): 1316-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953891&dopt=Abstract
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Modulation of the Fas signaling pathway by IFN-gamma in therapy of colon cancer: phase I trial and correlative studies of IFN-gamma, 5-fluorouracil, and leucovorin. Author(s): Schwartzberg LS, Petak I, Stewart C, Turner PK, Ashley J, Tillman DM, Douglas L, Tan M, Billups C, Mihalik R, Weir A, Tauer K, Shope S, Houghton JA. Source: Clin Cancer Res. 2002 August; 8(8): 2488-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171874&dopt=Abstract
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Molecular and clinical risk markers in colon cancer trials. Author(s): Hill MJ. Source: Eur J Cancer. 2000 June; 36(10): 1288-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10882868&dopt=Abstract
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Molecular and cytogenetic analysis of lymphoblastoid and colon cancer cell lines from cotton-top tamarin (Sagiunus oedipus). Author(s): Mao X, McGuire S, Hamoudi RA. Source: Cancer Genet Cytogenet. 2000 July 1; 120(1): 6-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10913670&dopt=Abstract
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Molecular causes of colon cancer. Author(s): Oving IM, Clevers HC. Source: Eur J Clin Invest. 2002 June; 32(6): 448-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12059991&dopt=Abstract
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Molecular downstream events and induction of thymidylate synthase in mutant and wild-type p53 colon cancer cell lines after treatment with 5-fluorouracil and the thymidylate synthase inhibitor raltitrexed. Author(s): Peters GJ, van Triest B, Backus HH, Kuiper CM, van der Wilt CL, Pinedo HM. Source: Eur J Cancer. 2000 May; 36(7): 916-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10785598&dopt=Abstract
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Molecular markers for colon cancer: where do we go from here? Author(s): Kulesz-Martin M. Source: Cancer Invest. 2000; 18(3): 287-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10754999&dopt=Abstract
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Molecular markers may improve colon cancer staging, screening. Author(s): McCann J. Source: J Natl Cancer Inst. 2000 July 5; 92(13): 1039-40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10880546&dopt=Abstract
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Molecular predictors of survival after adjuvant chemotherapy for colon cancer. Author(s): Watanabe T, Wu TT, Catalano PJ, Ueki T, Satriano R, Haller DG, Benson AB 3rd, Hamilton SR. Source: N Engl J Med. 2001 April 19; 344(16): 1196-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11309634&dopt=Abstract
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Molecular screening for colon cancer detection. Author(s): Villa E. Source: Dig Liver Dis. 2000 March; 32(2): 173-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10975793&dopt=Abstract
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Molecular screening for colon cancer in inflammatory bowel disease. Author(s): Malcomson RD, McGregor AH. Source: Eur J Gastroenterol Hepatol. 2002 October; 14(10): 1045-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12362091&dopt=Abstract
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Molecular staging of early colon cancer on the basis of sentinel node analysis: a multicenter phase II trial. Author(s): Bilchik AJ, Saha S, Wiese D, Stonecypher JA, Wood TF, Sostrin S, Turner RR, Wang HJ, Morton DL, Hoon DS. Source: J Clin Oncol. 2001 February 15; 19(4): 1128-36. Erratum In: J Clin Oncol 2001 May 1; 19(9): 2583. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11181678&dopt=Abstract
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Monensin-mediated growth inhibition of SNU-C1 colon cancer cells via cell cycle arrest and apoptosis. Author(s): Park WH, Kim ES, Jung CW, Kim BK, Lee YY. Source: Int J Oncol. 2003 February; 22(2): 377-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527937&dopt=Abstract
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Monoclonal antibodies recognizing epitopes of calretinins: dependence on Ca2+binding status and differences in antigen accessibility in colon cancer cells. Author(s): Zimmermann L, Schwaller B. Source: Cell Calcium. 2002 January; 31(1): 13-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11990296&dopt=Abstract
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Monoterpenes inhibit proliferation of human colon cancer cells by modulating cell cycle-related protein expression. Author(s): Bardon S, Foussard V, Fournel S, Loubat A. Source: Cancer Lett. 2002 July 26; 181(2): 187-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12175534&dopt=Abstract
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More (nodes) + more (analysis) = less (mortality): challenging the therapeutic equation for early-stage colon cancer. Author(s): Bilchik A. Source: Ann Surg Oncol. 2003 April; 10(3): 203-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679300&dopt=Abstract
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Morphologic progression of polypoid colon cancer invading muscularis propria. Author(s): Saito K, Arai K, Mori M. Source: Dig Dis Sci. 2000 June; 45(6): 1053-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10877215&dopt=Abstract
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Mortality trend of colon cancer in Japan: 1960-2000. Author(s): Marugame T, Hamashima C. Source: Jpn J Clin Oncol. 2003 June; 33(6): 320-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966937&dopt=Abstract
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MSH2 and MLH1 immunodetection and the prognosis of colon cancer. Author(s): Perrin J, Gouvernet J, Parriaux D, Noguchi T, Giovannini MH, Giovannini M, Delpero JR, Birnbaum D, Monges G. Source: Int J Oncol. 2001 November; 19(5): 891-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11604984&dopt=Abstract
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MSH6 and MSH3 are rarely involved in genetic predisposition to nonpolypotic colon cancer. Author(s): Huang J, Kuismanen SA, Liu T, Chadwick RB, Johnson CK, Stevens MW, Richards SK, Meek JE, Gao X, Wright FA, Mecklin JP, Jarvinen HJ, Gronberg H, Bisgaard ML, Lindblom A, Peltomaki P. Source: Cancer Res. 2001 February 15; 61(4): 1619-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11245474&dopt=Abstract
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Mucinous colon cancer. Author(s): Chang HS, Myung SJ, Yang SK. Source: Gastrointest Endosc. 2001 March; 53(3): 339. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11231395&dopt=Abstract
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Multifocal transitional cell carcinoma in a patient with hereditary nonpolyposis colon cancer. Author(s): Ong E, Joseph JV, Bramwell SP, Haites NE. Source: Bju Int. 2003 February; 91(3): 297. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581024&dopt=Abstract
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Multiple factors other than p53 influence colon cancer sensitivity to paclitaxel. Author(s): Sharma N, Ramachandran S, Bowers M, Yegappan M, Brown R, Aziz S, Chapman R, Yu BW. Source: Cancer Chemother Pharmacol. 2000; 46(4): 329-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11052631&dopt=Abstract
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Multiple inflammatory pseudotumors mimicking liver metastasis from colon cancer: report of a case. Author(s): Ishida H, Tatsuta M, Furukawa H, Ohta H, Hashimoto K, Hayashi N, Morimoto O, Ikeda M, Miya A, Masutani S, Kawasaki T, Satomi T, Yoshioka H, Hanai J. Source: Surg Today. 2000; 30(6): 530-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10883465&dopt=Abstract
256 Colon Cancer
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Multi-slice computed tomography as a screening tool for colon cancer, lung cancer and coronary artery disease. Author(s): Schoepf UJ, Becker CR, Obuchowski NA, Rust GF, Ohnesorge BM, Kohl G, Schaller S, Modic MT, Reiser MF. Source: Eur Radiol. 2001; 11(10): 1975-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11702131&dopt=Abstract
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Multivisceral resection for colon cancer. Author(s): Luna-Perez P, Rodriguez-Ramirez SE, De la Barrera MG, Zeferino M, Labastida S. Source: J Surg Oncol. 2002 June; 80(2): 100-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173378&dopt=Abstract
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Multivitamin use and colon cancer mortality in the Cancer Prevention Study II cohort (United States). Author(s): Jacobs EJ, Connell CJ, Patel AV, Chao A, Rodriguez C, Seymour J, McCullough ML, Calle EE, Thun MJ. Source: Cancer Causes Control. 2001 December; 12(10): 927-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11808712&dopt=Abstract
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Multivitamins, folate, and colon cancer. Author(s): Little J. Source: Gut. 2001 January; 48(1): 12-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11115816&dopt=Abstract
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Mutations spanning P53 exons 5-9 detected by non-isotopic RNAse cleavage assay and protein expression in human colon cancer. Author(s): Tommasi S, Abatangelo M, Lacalamita R, Montemurro S, Marzullo F, Paradiso A. Source: Cancer Genet Cytogenet. 2001 August; 129(1): 40-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11520564&dopt=Abstract
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NAT2, GSTM-1, cigarette smoking, and risk of colon cancer. Author(s): Slattery ML, Potter JD, Samowitz W, Bigler J, Caan B, Leppert M. Source: Cancer Epidemiol Biomarkers Prev. 1998 December; 7(12): 1079-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9865425&dopt=Abstract
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Natural history of sigmoid colon cancer: report of a patient observed for 4 years. Author(s): Tomiki Y, Kamano T, Hayashida Y, Takekawa S, Watanabe T, Tsurumaru M, Hirai S, Natsukawa S. Source: Endoscopy. 2001 March; 33(3): 280-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11293765&dopt=Abstract
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Necrotic infected liver metastasis from colon cancer. Author(s): Sarmiento JM, Sarr MG. Source: Surgery. 2002 July; 132(1): 110-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110807&dopt=Abstract
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Nemo-like kinase induces apoptosis in DLD-1 human colon cancer cells. Author(s): Yasuda J, Tsuchiya A, Yamada T, Sakamoto M, Sekiya T, Hirohashi S. Source: Biochem Biophys Res Commun. 2003 August 22; 308(2): 227-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901858&dopt=Abstract
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Neoangiogenesis in colon cancer: correlation between vascular density, vascular endothelial growth factor (VEGF) and p53 protein expression. Author(s): Faviana P, Boldrini L, Spisni R, Berti P, Galleri D, Biondi R, Camacci T, Materazzi G, Pingitore R, Miccoli P, Fontanini G. Source: Oncol Rep. 2002 May-June; 9(3): 617-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11956638&dopt=Abstract
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Neoplastic changes in saccharide sequence of dermatan sulfate chains derived from human colon cancer. Author(s): Daidouji K, Takagaki K, Yoshihara S, Matsuya H, Sasaki M, Endo M. Source: Dig Dis Sci. 2002 February; 47(2): 331-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11855549&dopt=Abstract
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Neoplastic progression in melanoma and colon cancer is associated with increased expression and activity of the interferon-inducible protein kinase, PKR. Author(s): Kim SH, Gunnery S, Choe JK, Mathews MB. Source: Oncogene. 2002 December 12; 21(57): 8741-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12483527&dopt=Abstract
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Neurotensin and a non-peptide neurotensin receptor antagonist control human colon cancer cell growth in cell culture and in cells xenografted into nude mice. Author(s): Maoret JJ, Anini Y, Rouyer-Fessard C, Gully D, Laburthe M. Source: Int J Cancer. 1999 January 29; 80(3): 448-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9935189&dopt=Abstract
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New adjuvant therapy for colon cancer: justified hope or commercial hype. Author(s): Galanis E, Alberts SR, O'Connell MJ. Source: Surg Oncol Clin N Am. 2000 October; 9(4): 813-23; Discussion 825-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11008249&dopt=Abstract
258 Colon Cancer
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New therapeutic options in colon cancer: focus on oxaliplatin. Author(s): Wilkes GM. Source: Clin J Oncol Nurs. 2002 May-June; 6(3): 131-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11998605&dopt=Abstract
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Nitric oxide induces cyclooxygenase expression and inhibits cell growth in colon cancer cell lines. Author(s): Liu Q, Chan ST, Mahendran R. Source: Carcinogenesis. 2003 April; 24(4): 637-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727790&dopt=Abstract
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Nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NSAIDs) alter the kinetics of human colon cancer cell lines more effectively than traditional NSAIDs: implications for colon cancer chemoprevention. Author(s): Williams JL, Borgo S, Hasan I, Castillo E, Traganos F, Rigas B. Source: Cancer Res. 2001 April 15; 61(8): 3285-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11309281&dopt=Abstract
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Nitrogen mustard up-regulates Bcl-2 and GSH and increases NTP and PCr in HT-29 colon cancer cells. Author(s): Boddie AW Jr, Constantinou A, Williams C, Reed A. Source: Br J Cancer. 1998 May; 77(9): 1395-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9652754&dopt=Abstract
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Nk4, a new HGF/SF variant, is an antagonist to the influence of HGF/SF on the motility and invasion of colon cancer cells. Author(s): Parr C, Hiscox S, Nakamura T, Matsumoto K, Jiang WG. Source: Int J Cancer. 2000 February 15; 85(4): 563-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10699931&dopt=Abstract
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No apparent increase of colon cancer in relatives of ulcerative colitis patients. Author(s): Han SW, Barton JR, Welfare MR. Source: Am J Gastroenterol. 1999 August; 94(8): 2323-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10445585&dopt=Abstract
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No association between colon cancer and adenocarcinoma of the oesophagus in a population based cohort study in Sweden. Author(s): Lagergren J, Nyren O. Source: Gut. 1999 June; 44(6): 819-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10323883&dopt=Abstract
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No evidence of correlation between mutation at codon 531 of src and the risk of colon cancer in Chinese. Author(s): Wang NM, Yeh KT, Tsai CH, Chen SJ, Chang JG. Source: Cancer Lett. 2000 March 31; 150(2): 201-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10704743&dopt=Abstract
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Non-Hodgkin's lymphoma in a patient with probable hereditary nonpolyposis colon cancer: report of a case and review of the literature. Author(s): Hirano K, Yamashita K, Yamashita N, Nakatsumi Y, Esumi H, Kawashima A, Ohta T, Mai M, Minamoto T. Source: Dis Colon Rectum. 2002 February; 45(2): 273-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11852345&dopt=Abstract
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Nonproteic antioxidant status in plasma of subjects with colon cancer. Author(s): Di Giacomo C, Acquaviva R, Lanteri R, Licata F, Licata A, Vanella A. Source: Exp Biol Med (Maywood). 2003 May; 228(5): 525-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709580&dopt=Abstract
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Nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenases, and the cell cycle. Their interactions in colon cancer. Author(s): Rigas B, Shiff SJ. Source: Adv Exp Med Biol. 1999; 470: 119-26. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10709681&dopt=Abstract
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Nonsteroidal anti-inflammatory drugs may prevent colon cancer through suppression of hepatocyte growth factor expression. Author(s): Ota S, Tanaka Y, Bamba H, Kato A, Matsuzaki F. Source: Eur J Pharmacol. 1999 February 12; 367(1): 131-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10082276&dopt=Abstract
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Nonsteroidal anti-inflammatory drugs stimulate spermidine/spermine acetyltransferase and deplete polyamine content in colon cancer cells. Author(s): Turchanowa L, Dauletbaev N, Milovic V, Stein J. Source: Eur J Clin Invest. 2001 October; 31(10): 887-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11737227&dopt=Abstract
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NO-releasing NSAIDs and colon cancer chemoprevention: a promising novel approach (Review). Author(s): Rigas B, Williams JL. Source: Int J Oncol. 2002 May; 20(5): 885-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11956579&dopt=Abstract
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Novel 19-nor-hexafluoride vitamin D3 analog (Ro 25-6760) inhibits human colon cancer in vitro via apoptosis. Author(s): Evans SR, Soldatenkov V, Shchepotin EB, Bogrash E, Shchepotin IB. Source: Int J Oncol. 1999 May; 14(5): 979-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10200351&dopt=Abstract
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Novel colon cancer cell lines leading to better understanding of the diversity of respective primary cancers. Author(s): Vecsey-Semjen B, Becker KF, Sinski A, Blennow E, Vietor I, Zatloukal K, Beug H, Wagner E, Huber LA. Source: Oncogene. 2002 July 11; 21(30): 4646-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12096341&dopt=Abstract
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Novel detection and differential utilization of a c-myc transcriptional block in colon cancer chemoprevention. Author(s): Wilson AJ, Velcich A, Arango D, Kurland AR, Shenoy SM, Pezo RC, Levsky JM, Singer RH, Augenlicht LH. Source: Cancer Res. 2002 November 1; 62(21): 6006-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414619&dopt=Abstract
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Nr-CAM is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis. Author(s): Conacci-Sorrell ME, Ben-Yedidia T, Shtutman M, Feinstein E, Einat P, BenZe'ev A. Source: Genes Dev. 2002 August 15; 16(16): 2058-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183361&dopt=Abstract
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Nuclear beta-catenin in colorectal tumors: to freeze or not to freeze? Colon Cancer Team at IMAS. Author(s): Munne A, Fabre M, Marinoso ML, Gallen M, Real FX. Source: J Histochem Cytochem. 1999 August; 47(8): 1089-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10424893&dopt=Abstract
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Nuclear factor kappaB inhibitors induce adhesion-dependent colon cancer apoptosis: implications for metastasis. Author(s): Scaife CL, Kuang J, Wills JC, Trowbridge DB, Gray P, Manning BM, Eichwald EJ, Daynes RA, Kuwada SK. Source: Cancer Res. 2002 December 1; 62(23): 6870-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12460901&dopt=Abstract
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Nuclear matrix protein alterations associated with colon cancer metastasis to the liver. Author(s): Brunagel G, Schoen RE, Bauer AJ, Vietmeier BN, Getzenberg RH. Source: Clin Cancer Res. 2002 October; 8(10): 3039-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374670&dopt=Abstract
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Nuclear matrix proteins as proteomic markers of preneoplastic and cancer lesions : commentary re: G. Brunagel et al., nuclear matrix protein alterations associated with colon cancer metastasis to the liver. Clin. Cancer Res., 8: 3039-3045, 2002. Author(s): Coffey DS. Source: Clin Cancer Res. 2002 October; 8(10): 3031-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374668&dopt=Abstract
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Nutrition and colon cancer prevention. Author(s): Bostick RM. Source: Nestle Nutr Workshop Ser Clin Perform Programme. 2000; 4: 67-85; Discussion 85-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11490583&dopt=Abstract
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Nutrition, energy balance and colon cancer risk: the role of insulin and insulin-like growth factor-I. Author(s): Kaaks R. Source: Iarc Sci Publ. 2002; 156: 289-93. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12484189&dopt=Abstract
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Nutritional chemoprevention of colon cancer. Author(s): Mason JB. Source: Semin Gastrointest Dis. 2002 July; 13(3): 143-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230317&dopt=Abstract
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Nutritional status of folate and colon cancer risk: evidence from NHANES I epidemiologic follow-up study. Author(s): Su LJ, Arab L. Source: Ann Epidemiol. 2001 January; 11(1): 65-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11164122&dopt=Abstract
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Obesity, gender, and colon cancer. Author(s): Giovannucci E. Source: Gut. 2002 August; 51(2): 147. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117867&dopt=Abstract
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Obstructive ileitis secondary to colon cancer: report of a case. Author(s): Matsuda T, Taniguchi F, Tsuda T, Aikawa I. Source: Surg Today. 2003; 33(3): 205-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12658388&dopt=Abstract
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Occlusion of the left superficial femoral artery during hepatic arterial infusion of chemotherapy for liver metastases from colon cancer 18 months after the implantation of a port system: a case report. Author(s): Imai R, Ito K, Ishigami N, Oba N, Nakajima N. Source: Jpn J Clin Oncol. 2002 February; 32(2): 68-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11948232&dopt=Abstract
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Occult colon cancer in a patient with an unexplained episode of pulmonary embolism. Author(s): Caputo F, Musardo G, Savini P, Balducci G, Marchi G, Corbelli C, Bernardi M, Addolorato G, Stefanini GF. Source: Hepatogastroenterology. 2000 January-February; 47(31): 165-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10690603&dopt=Abstract
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On call. I've read that aspirin may help prevent colon cancer as well as heart attacks. I take an aspirin every day, and I wonder if it may also help with prostate cancer. Author(s): Simon HB. Source: Harv Mens Health Watch. 2002 November; 7(4): 8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453742&dopt=Abstract
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On the web. Colon cancer...click by click. Author(s): Cavallo J. Source: Intouch. 2002 March; 4(2): 16-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398034&dopt=Abstract
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Oncogenic beta-catenin and MMP-7 (matrilysin) cosegregate in late-stage clinical colon cancer. Author(s): Ougolkov AV, Yamashita K, Mai M, Minamoto T. Source: Gastroenterology. 2002 January; 122(1): 60-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11781281&dopt=Abstract
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Oncogenic Ki-ras confers a more aggressive colon cancer phenotype through modification of transforming growth factor-beta receptor III. Author(s): Yan Z, Deng X, Friedman E. Source: J Biol Chem. 2001 January 12; 276(2): 1555-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11029459&dopt=Abstract
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Oncogenic ras induces gastrin gene expression in colon cancer. Author(s): Nakata H, Wang SL, Chung DC, Westwick JK, Tillotson LG. Source: Gastroenterology. 1998 November; 115(5): 1144-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9797369&dopt=Abstract
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Oncolytic reovirus against ovarian and colon cancer. Author(s): Hirasawa K, Nishikawa SG, Norman KL, Alain T, Kossakowska A, Lee PW. Source: Cancer Res. 2002 March 15; 62(6): 1696-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11912142&dopt=Abstract
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Ontario familial colon cancer registry: methods and first-year response rates. Author(s): Cotterchio M, McKeown-Eyssen G, Sutherland H, Buchan G, Aronson M, Easson AM, Macey J, Holowaty E, Gallinger S. Source: Chronic Dis Can. 2000; 21(2): 81-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11007659&dopt=Abstract
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Opposite effects on human colon cancer cell proliferation of two dietary ThomsenFriedenreich antigen-binding lectins. Author(s): Yu LG, Milton JD, Fernig DG, Rhodes JM. Source: J Cell Physiol. 2001 February; 186(2): 282-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11169464&dopt=Abstract
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Ossifying intramuscular metastasis from colon cancer: report of a case. Author(s): Yoshikawa H, Kameyama M, Ueda T, Kudawara I, Nakanishi K. Source: Dis Colon Rectum. 1999 September; 42(9): 1225-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10496567&dopt=Abstract
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Osteopontin and colon cancer progression. Author(s): Yeatman TJ, Chambers AF. Source: Clin Exp Metastasis. 2003; 20(1): 85-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650611&dopt=Abstract
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Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profiling. Author(s): Agrawal D, Chen T, Irby R, Quackenbush J, Chambers AF, Szabo M, Cantor A, Coppola D, Yeatman TJ. Source: J Natl Cancer Inst. 2002 April 3; 94(7): 513-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11929952&dopt=Abstract
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Outcomes among African-Americans and Caucasians in colon cancer adjuvant therapy trials: findings from the National Surgical Adjuvant Breast and Bowel Project. Author(s): Dignam JJ, Colangelo L, Tian W, Jones J, Smith R, Wickerham DL, Wolmark N. Source: J Natl Cancer Inst. 1999 November 17; 91(22): 1933-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10564677&dopt=Abstract
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Outcomes and toxicity in african-american and caucasian patients in a randomized adjuvant chemotherapy trial for colon cancer. Author(s): McCollum AD, Catalano PJ, Haller DG, Mayer RJ, Macdonald JS, Benson AB 3rd, Fuchs CS. Source: J Natl Cancer Inst. 2002 August 7; 94(15): 1160-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12165641&dopt=Abstract
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Overexpression of Kruppel-like factor 4 in the human colon cancer cell line RKO leads to reduced tumorigenecity. Author(s): Dang DT, Chen X, Feng J, Torbenson M, Dang LH, Yang VW. Source: Oncogene. 2003 May 29; 22(22): 3424-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776194&dopt=Abstract
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Overexpression of normal c-Src in poorly metastatic human colon cancer cells enhances primary tumor growth but not metastatic potential. Author(s): Irby R, Mao W, Coppola D, Jove R, Gamero A, Cuthbertson D, Fujita DJ, Yeatman TJ. Source: Cell Growth Differ. 1997 December; 8(12): 1287-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9419417&dopt=Abstract
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Overexpression of pterin-4a-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor 1 in human colon cancer. Author(s): Eskinazi R, Thony B, Svoboda M, Robberecht P, Dassesse D, Heizmann CW, Van Laethem JL, Resibois A. Source: Am J Pathol. 1999 October; 155(4): 1105-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10514393&dopt=Abstract
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Overexpression of ribosomal proteins L4 and L5 and the putative alternative elongation factor PTI-1 in the doxorubicin resistant human colon cancer cell line LoVoDxR. Author(s): Bertram J, Palfner K, Hiddemann W, Kneba M. Source: Eur J Cancer. 1998 April; 34(5): 731-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9713282&dopt=Abstract
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Overexpression of the thymosin beta-4 gene is associated with malignant progression of SW480 colon cancer cells. Author(s): Wang WS, Chen PM, Hsiao HL, Ju SY, Su Y. Source: Oncogene. 2003 May 22; 22(21): 3297-306. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12761500&dopt=Abstract
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Overexpression of the wild-type p53 gene inhibits NF-kappaB activity and synergizes with aspirin to induce apoptosis in human colon cancer cells. Author(s): Shao J, Fujiwara T, Kadowaki Y, Fukazawa T, Waku T, Itoshima T, Yamatsuji T, Nishizaki M, Roth JA, Tanaka N. Source: Oncogene. 2000 February 10; 19(6): 726-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10698490&dopt=Abstract
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Oxygen free radical generating mechanisms in the colon: do the semiquinones of vitamin K play a role in the aetiology of colon cancer? Author(s): Valko M, Morris H, Mazur M, Rapta P, Bilton RF. Source: Biochim Biophys Acta. 2001 August 15; 1527(3): 161-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11479033&dopt=Abstract
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P14 methylation in human colon cancer is associated with microsatellite instability and wild-type p53. Author(s): Shen L, Kondo Y, Hamilton SR, Rashid A, Issa JP. Source: Gastroenterology. 2003 March; 124(3): 626-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612901&dopt=Abstract
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P53 codon 72 genotypes in colon cancer. Association with human papillomavirus infection. Author(s): Sayhan N, Yazici H, Budak M, Bitisik O, Dalay N. Source: Res Commun Mol Pathol Pharmacol. 2001 July; 109(1-2): 25-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11458982&dopt=Abstract
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p53 gene transfer does not enhance E2F-1-mediated apoptosis in human colon cancer cells. Author(s): Draus JM, Elliott MJ, Atienza C Jr, Stilwell A, Wong SL, Dong Y, Yang H, McMasters KM. Source: Exp Mol Med. 2001 December 31; 33(4): 209-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11795482&dopt=Abstract
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P53 modulates the effect of loss of DNA mismatch repair on the sensitivity of human colon cancer cells to the cytotoxic and mutagenic effects of cisplatin. Author(s): Lin X, Ramamurthi K, Mishima M, Kondo A, Christen RD, Howell SB. Source: Cancer Res. 2001 February 15; 61(4): 1508-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11245458&dopt=Abstract
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p53-dependent transcriptional regulation of the APC promoter in colon cancer cells treated with DNA alkylating agents. Author(s): Jaiswal AS, Narayan S. Source: J Biol Chem. 2001 May 25; 276(21): 18193-9. Epub 2001 March 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11279192&dopt=Abstract
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Parathyroid hormone-related protein overexpression in the human colon cancer cell line HT-29 enhances adhesion of the cells to collagen type I. Author(s): Ye Y, Seitz PK, Cooper CW. Source: Regul Pept. 2001 September 15; 101(1-3): 19-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11495675&dopt=Abstract
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Participation rates of Ashkenazi Jews in a colon cancer community-based screening/prevention study. Author(s): Cappelli M, Hunter AG, Stern H, Humphreys L, Van Houten L, O'Rourke K, Viertelhausen S, Perras H, Lagarde AE. Source: Clin Genet. 2002 February; 61(2): 104-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11940085&dopt=Abstract
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Patchy field defects of apoptosis resistance and dedifferentiation in flat mucosa of colon resections from colon cancer patients. Author(s): Bernstein H, Holubec H, Warneke JA, Garewal H, Earnest DL, Payne CM, Roe DJ, Cui H, Jacobson EL, Bernstein C. Source: Ann Surg Oncol. 2002 June; 9(5): 505-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12052764&dopt=Abstract
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Patient experience and preferences toward colon cancer screening: a comparison of virtual colonoscopy and conventional colonoscopy. Author(s): Akerkar GA, Yee J, Hung R, McQuaid K. Source: Gastrointest Endosc. 2001 September; 54(3): 310-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522970&dopt=Abstract
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Pelvic kidney mimicking recurrent colon cancer on FDG positron emission tomographic imaging. Author(s): Bhargava P, Zhuang H, Hickeson M, Alavi A. Source: Clin Nucl Med. 2002 August; 27(8): 602-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12170012&dopt=Abstract
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Perceived barriers and benefits to colon cancer screening among African Americans in North Carolina: how does perception relate to screening behavior? Author(s): James AS, Campbell MK, Hudson MA. Source: Cancer Epidemiol Biomarkers Prev. 2002 June; 11(6): 529-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12050093&dopt=Abstract
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Peritoneal involvement in stage II colon cancer. Author(s): Lennon AM, Mulcahy HE, Hyland JM, Lowry C, White A, Fennelly D, Murphy JJ, O'Donoghue DP, Sheahan K. Source: Am J Clin Pathol. 2003 January; 119(1): 108-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520705&dopt=Abstract
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Peroxisome proliferator-activated receptor gamma-mediated differentiation: a mutation in colon cancer cells reveals divergent and cell type-specific mechanisms. Author(s): Gupta RA, Sarraf P, Mueller E, Brockman JA, Prusakiewicz JJ, Eng C, Willson TM, DuBois RN. Source: J Biol Chem. 2003 June 20; 278(25): 22669-77. Epub 2003 February 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591919&dopt=Abstract
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Perturbation by geraniol of cell membrane permeability and signal transduction pathways in human colon cancer cells. Author(s): Carnesecchi S, Bradaia A, Fischer B, Coelho D, Scholler-Guinard M, Gosse F, Raul F. Source: J Pharmacol Exp Ther. 2002 November; 303(2): 711-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12388655&dopt=Abstract
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Phase I study on sentinel lymph node mapping in colon cancer: a preliminary report. Author(s): Bendavid Y, Latulippe JF, Younan RJ, Leclerc YE, Dube S, Heyen F, Morin M, Girard R, Bastien E, Ferreira J, Cerino M, Dube P. Source: J Surg Oncol. 2002 February; 79(2): 81-4; Discussion 85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11815993&dopt=Abstract
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Phenylbutyrate-induced apoptosis is associated with inactivation of NF-kappaB IN HT-29 colon cancer cells. Author(s): Feinman R, Clarke KO, Harrison LE. Source: Cancer Chemother Pharmacol. 2002 January; 49(1): 27-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11855750&dopt=Abstract
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Phlegmonous enteritis in a patient with congestive heart failure and colon cancer. Author(s): Namkung S, Yoo YS, Hwang IK, Kim BS, Bae SH, Choi YH. Source: Korean J Radiol. 2001 October-December; 2(4): 235-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11754332&dopt=Abstract
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Physical activity and colon cancer. A systematic review of potential mechanisms. Author(s): Quadrilatero J, Hoffman-Goetz L. Source: J Sports Med Phys Fitness. 2003 June; 43(2): 121-38. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853893&dopt=Abstract
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Physical activity and colon cancer: confounding or interaction? Author(s): Slattery ML, Potter JD. Source: Med Sci Sports Exerc. 2002 June; 34(6): 913-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12048315&dopt=Abstract
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Physician compliance with colon cancer screening. Author(s): Malik J, Sansone RA. Source: Am J Gastroenterol. 2002 April; 97(4): 1078-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003406&dopt=Abstract
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PMEPA1, a transforming growth factor-beta-induced marker of terminal colonocyte differentiation whose expression is maintained in primary and metastatic colon cancer. Author(s): Brunschwig EB, Wilson K, Mack D, Dawson D, Lawrence E, Willson JK, Lu S, Nosrati A, Rerko RM, Swinler S, Beard L, Lutterbaugh JD, Willis J, Platzer P, Markowitz S. Source: Cancer Res. 2003 April 1; 63(7): 1568-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670906&dopt=Abstract
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Point: From animal models to prevention of colon cancer. Systematic review of chemoprevention in min mice and choice of the model system. Author(s): Corpet DE, Pierre F. Source: Cancer Epidemiol Biomarkers Prev. 2003 May; 12(5): 391-400. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750232&dopt=Abstract
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Polyamines and colon cancer. Author(s): Wallace HM, Caslake R. Source: Eur J Gastroenterol Hepatol. 2001 September; 13(9): 1033-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11564951&dopt=Abstract
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Polyethylene glycol induces apoptosis in HT-29 cells: potential mechanism for chemoprevention of colon cancer. Author(s): Roy HK, DiBaise JK, Black J, Karolski WJ, Ratashak A, Ansari S. Source: Febs Lett. 2001 May 11; 496(2-3): 143-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11356199&dopt=Abstract
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Polymyositis successfully treated with surgical resection of colon cancer. Author(s): Tagawa A, Kashima R, Kaneda K, Nakayama M, Ono S, Shimizu N. Source: Eur Neurol. 2000; 44(4): 251-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11096228&dopt=Abstract
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Population-based fecal occult blood screening for colon cancer: will the benefits outweigh the harm? Author(s): Marshall KG. Source: Cmaj. 2000 September 5; 163(5): 545-6; Discussion 547. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11006766&dopt=Abstract
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Port site metastasis of sigmoid colon cancer after a laparoscopic sigmoidectomy: report of a case. Author(s): Itano O, Watanabe T, Jinno H, Suzuki F, Baba H, Otaka H. Source: Surg Today. 2003; 33(5): 379-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734736&dopt=Abstract
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Positron emission tomography in intussusception of colon cancer, where computed tomography failed. Author(s): Kaminski CY, Kaminski JM, Guttentag AR, Tran H. Source: Clin Nucl Med. 2003 January; 28(1): 60-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12493969&dopt=Abstract
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Possible mechanisms relating diet and risk of colon cancer. Author(s): Bruce WR, Giacca A, Medline A. Source: Cancer Epidemiol Biomarkers Prev. 2000 December; 9(12): 1271-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11142411&dopt=Abstract
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Potential role and chronology of abnormal expression of the Deleted in Colon Cancer (DCC) and the p53 proteins in the development of gastric cancer. Author(s): Graziano F, Cascinu S, Staccioli MP, Catalano V, Rossi MC, Baldelli AM, Giordani P, Muretto P, Catalano G. Source: Bmc Cancer. 2001; 1(1): 9. Epub 2001 August 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11518545&dopt=Abstract
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Preoperative anemia in colon cancer: assessment of risk factors. Author(s): Dunne JR, Gannon CJ, Osborn TM, Taylor MD, Malone DL, Napolitano LM. Source: Am Surg. 2002 June; 68(6): 582-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12079143&dopt=Abstract
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Preoperative mobilization of circulating dendritic cells by Flt3 ligand administration to patients with metastatic colon cancer. Author(s): Morse MA, Nair S, Fernandez-Casal M, Deng Y, St Peter M, Williams R, Hobeika A, Mosca P, Clay T, Cumming RI, Fisher E, Clavien P, Proia AD, Niedzwiecki D, Caron D, Lyerly HK. Source: J Clin Oncol. 2000 December 1; 18(23): 3883-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11099317&dopt=Abstract
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Preventing colon cancer. Screening and early detection save lives. Author(s): Hall LL. Source: Fda Consum. 2000 November-December; 34(6): 14-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11192813&dopt=Abstract
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Prevention of colon cancer with ursodiol in ulcerative colitis. Author(s): Kim HS. Source: Inflamm Bowel Dis. 2001 August; 7(3): 279-80. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11515858&dopt=Abstract
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Prevention of liver metastasis of human colon cancer by selective matrix metalloproteinase inhibitor MMI-166. Author(s): Oba K, Konno H, Tanaka T, Baba M, Kamiya K, Ohta M, Kaneko T, Shouji T, Igarashi A, Nakamura S. Source: Cancer Lett. 2002 January 10; 175(1): 45-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11734335&dopt=Abstract
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Preventive potential of wheat bran fractions against experimental colon carcinogenesis: implications for human colon cancer prevention. Author(s): Reddy BS, Hirose Y, Cohen LA, Simi B, Cooma I, Rao CV. Source: Cancer Res. 2000 September 1; 60(17): 4792-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10987288&dopt=Abstract
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Preventive surgery for colon cancer in familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer syndrome. Author(s): Moslein G, Pistorius S, Saeger HD, Schackert HK. Source: Langenbecks Arch Surg. 2003 March; 388(1): 9-16. Epub 2003 March 27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690475&dopt=Abstract
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Prodigiosin-induced apoptosis in human colon cancer cells. Author(s): Montaner B, Perez-Tomas R. Source: Life Sci. 2001 March 16; 68(17): 2025-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11388704&dopt=Abstract
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Prognosis with colon cancer improves with wide resection of the mesentery to include many lymph nodes. Author(s): Spratt JS. Source: Ann Surg Oncol. 2003 July; 10(6): 711. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839858&dopt=Abstract
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Prognostic evaluation of stage B colon cancer patients is improved by an adequate lymphadenectomy: results of a secondary analysis of a large scale adjuvant trial. Author(s): Prandi M, Lionetto R, Bini A, Francioni G, Accarpio G, Anfossi A, Ballario E, Becchi G, Bonilauri S, Carobbi A, Cavaliere P, Garcea D, Giuliani L, Morziani E, Mosca F, Mussa A, Pasqualini M, Poddie D, Tonetti F, Zardo L, Rosso R. Source: Ann Surg. 2002 April; 235(4): 458-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923600&dopt=Abstract
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Prognostic role of K-ras in patients with progressive colon cancer who received treatment with Marimastat (BB2516). Author(s): Nemunaitis J, Cox J, Hays S, Meyer W, Kebart R, Ognoskie N, Courtney A, Yu Y, Rasmussen H, Tong A. Source: Cancer Invest. 2000; 18(3): 185-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10754986&dopt=Abstract
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Prognostic significance of circulating IL-10 and IL-6 serum levels in colon cancer patients undergoing surgery. Author(s): Galizia G, Orditura M, Romano C, Lieto E, Castellano P, Pelosio L, Imperatore V, Catalano G, Pignatelli C, De Vita F. Source: Clin Immunol. 2002 February; 102(2): 169-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11846459&dopt=Abstract
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Prognostic significance of K-ras and TP53 mutations in the role of adjuvant chemotherapy on survival in patients with Dukes C colon cancer. Author(s): Bleeker WA, Hayes VM, Karrenbeld A, Hofstra RM, Verlind E, Hermans J, Poppema S, Buys CH, Plukker JT. Source: Dis Colon Rectum. 2001 March; 44(3): 358-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11289281&dopt=Abstract
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Prognostic significance of occult metastases in colon cancer. Author(s): Merrie AE, van Rij AM, Dennett ER, Phillips LV, Yun K, McCall JL. Source: Dis Colon Rectum. 2003 February; 46(2): 221-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576896&dopt=Abstract
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Prognostic significance of p53 mutations in colon cancer at the population level. Author(s): Samowitz WS, Curtin K, Ma KN, Edwards S, Schaffer D, Leppert MF, Slattery ML. Source: Int J Cancer. 2002 June 1; 99(4): 597-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992552&dopt=Abstract
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Prognostic value of various staging and grading systems in proximal colon cancer. Author(s): Hilska M, Collan Y, Roberts PJ, Ovaska J, Kossi J, Paajanen H, Laato M. Source: Eur J Surg. 2002; 168(2): 84-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12113276&dopt=Abstract
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Prolonged activation of mitogen-activated protein kinases during NSAID-induced apoptosis in HT-29 colon cancer cells. Author(s): Kim TI, Jin SH, Kim WH, Kang EH, Choi KY, Kim HJ, Shin SK, Kang JK. Source: Int J Colorectal Dis. 2001 June; 16(3): 167-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11459290&dopt=Abstract
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Proportion of colon cancer risk that might be preventable in a cohort of middle-aged US men. Author(s): Platz EA, Willett WC, Colditz GA, Rimm EB, Spiegelman D, Giovannucci E. Source: Cancer Causes Control. 2000 August; 11(7): 579-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10977102&dopt=Abstract
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Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy. Author(s): Pai R, Soreghan B, Szabo IL, Pavelka M, Baatar D, Tarnawski AS. Source: Nat Med. 2002 March; 8(3): 289-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11875501&dopt=Abstract
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Prostaglandins promote colon cancer cell invasion; signaling by cross-talk between two distinct growth factor receptors. Author(s): Pai R, Nakamura T, Moon WS, Tarnawski AS. Source: Faseb J. 2003 September; 17(12): 1640-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12958170&dopt=Abstract
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Protective role of probiotics and prebiotics in colon cancer. Author(s): Wollowski I, Rechkemmer G, Pool-Zobel BL. Source: Am J Clin Nutr. 2001 February; 73(2 Suppl): 451S-455S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11157356&dopt=Abstract
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Proteome analysis of butyrate-treated human colon cancer cells (HT-29). Author(s): Tan S, Seow TK, Liang RC, Koh S, Lee CP, Chung MC, Hooi SC. Source: Int J Cancer. 2002 April 1; 98(4): 523-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920611&dopt=Abstract
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Pseudo-Meigs' syndrome caused by ovarian metastasis from colon cancer: report of a case. Author(s): Ohsawa T, Ishida H, Nakada H, Inokuma S, Hashimoto D, Kuroda H, Itoyama S. Source: Surg Today. 2003; 33(5): 387-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734738&dopt=Abstract
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Purulent pericarditis caused by group G streptococcus as an initial presentation of colon cancer. Author(s): Kim NH, Park JP, Jeon SH, Lee YJ, Choi HJ, Jeong KM, Lee JG, Choi SP, Lim JH, Kim YH, Kim YS, Kim YM, Hwang MH, Cho JW, Moon Y, Oh SK, Jeong JW. Source: J Korean Med Sci. 2002 August; 17(4): 571-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172060&dopt=Abstract
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Putative colon cancer risk factors damage global DNA and TP53 in primary human colon cells isolated from surgical samples. Author(s): Schaeferhenrich A, Sendt W, Scheele J, Kuechler A, Liehr T, Claussen U, Rapp A, Greulich KO, Pool-Zobel BL. Source: Food Chem Toxicol. 2003 May; 41(5): 655-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659718&dopt=Abstract
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Qigong therapy in the treatment of metastatic colon cancer. Author(s): Loh SH. Source: Altern Ther Health Med. 1999 July; 5(4): 112, 111. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10394680&dopt=Abstract
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Quality of life as subjective experience: reframing of perception in patients with colon cancer undergoing radical resection with or without adjuvant chemotherapy. Swiss Group for Clinical Cancer Research (SAKK) Author(s): Bernhard J, Hurny C, Maibach R, Herrmann R, Laffer U. Source: Ann Oncol. 1999 July; 10(7): 775-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10470423&dopt=Abstract
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Quality of life in breast and colon cancer long-term survivors: an assessment with the EORTC QLQ-C30 and SF-36 questionnaires. Author(s): Mosconi P, Apolone G, Barni S, Secondino S, Sbanotto A, Filiberti A. Source: Tumori. 2002 March-April; 88(2): 110-6. Erratum In: Tumori 2002 July-August; 88(4): 352. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088249&dopt=Abstract
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Quantitative analysis of vascular endothelial growth factor in colon cancer. Clinical and experimental. Author(s): Konno H, Tanaka T, Baba M, Kanai T, Matsumoto K, Kamiya K, Nakamura S, Baba S. Source: Eur Surg Res. 1998; 30(4): 273-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9704754&dopt=Abstract
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Quantitative assessment of spontaneous lung metastases of human HT29 colon cancer cells transplanted into SCID mice. Author(s): Jojovic M, Schumacher U. Source: Cancer Lett. 2000 May 1; 152(2): 151-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10773406&dopt=Abstract
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Quercetin inhibits p21-RAS expression in human colon cancer cell lines and in primary colorectal tumors. Author(s): Ranelletti FO, Maggiano N, Serra FG, Ricci R, Larocca LM, Lanza P, Scambia G, Fattorossi A, Capelli A, Piantelli M. Source: Int J Cancer. 2000 February 1; 85(3): 438-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10652438&dopt=Abstract
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Quest for new and better colon cancer treatments picks up steam. Author(s): Nelson NJ. Source: J Natl Cancer Inst. 1998 December 16; 90(24): 1858-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9862617&dopt=Abstract
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Radiation-induced changes in nucleotide metabolism of two colon cancer cell lines with different radiosensitivities. Author(s): Wei S, Ageron-Blanc A, Petridis F, Beaumatin J, Bonnet S, Luccioni C. Source: Int J Radiat Biol. 1999 August; 75(8): 1005-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10465366&dopt=Abstract
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Radioimmunotherapy of human colon cancer xenografts using a dimeric single-chain Fv antibody construct. Author(s): Pavlinkova G, Booth BJ, Batra SK, Colcher D. Source: Clin Cancer Res. 1999 September; 5(9): 2613-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10499640&dopt=Abstract
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Radioimmunotherapy with 186Re-labeled monoclonal antibody to treat liver metastases of colon cancer cells in nude mice. Author(s): Kinuya S, Yokoyama K, Kawashima A, Izumo M, Sorita T, Obata T, Watanabe N, Shuke N, Bunko H, Michigishi T, Tonami N. Source: Cancer Biother Radiopharm. 2002 December; 17(6): 681-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537672&dopt=Abstract
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Randomized clinical trials in colon cancer. Author(s): Shoup MC, Nissan A, Dangelica MI, Tschmelitsch J. Source: Surg Oncol Clin N Am. 2002 January; 11(1): 133-48, Ix. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11928797&dopt=Abstract
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Rapid adhesion and spread of non-adherent colon cancer Colo201 cells induced by the protein kinase inhibitors, K252a and KT5720 and suppression of the adhesion by the immunosuppressants FK506 and cyclosporin A. Author(s): Mohri T, Kameshita I, Suzuki S, Hioki K, Tokunaga R, Takatani S. Source: Cell Struct Funct. 1998 October; 23(5): 255-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9872566&dopt=Abstract
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Rapid diagnostic test for hereditary nonpolyposis colon cancer kindred using polymerase chain reaction. Author(s): Faragher IG, Whitehead RH. Source: Dis Colon Rectum. 1998 July; 41(7): 938-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9678385&dopt=Abstract
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Rapid growth of a retroperitoneal rhabdomyosarcoma following right hemicolectomy for ascending colon cancer: report of a case. Author(s): Kunieda K, Saji S, Kuwabara I, Watanabe A, Katoh M, Sugiyama Y, Shimokawa K. Source: Surg Today. 2000; 30(4): 372-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10795872&dopt=Abstract
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Rarity of colon cancer in Africans is associated with low animal product consumption, not fiber. Author(s): O'Keefe SJ, Kidd M, Espitalier-Noel G, Owira P. Source: Am J Gastroenterol. 1999 May; 94(5): 1373-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10235221&dopt=Abstract
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Re: "Eating patterns and risk of colon cancer". Author(s): Tseng M, Morgenstern H. Source: Am J Epidemiol. 1999 June 1; 149(11): 1074-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10355386&dopt=Abstract
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Re: Association between hemochromatosis (HFE) gene mutation carrier status and the risk of colon cancer. Author(s): Sullivan JL. Source: J Natl Cancer Inst. 2003 June 4; 95(11): 829-30; Author Reply 830. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12783939&dopt=Abstract
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Re: Calcium intake and risk of colon cancer in women and men. Author(s): Newmark HL, Shiff SJ. Source: J Natl Cancer Inst. 2003 January 15; 95(2): 169; Author Reply 169-70. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529351&dopt=Abstract
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Readers bring attention to value of surgical intervention in treating colon cancer. Author(s): Pack DA, Hefferman NM. Source: Clin J Oncol Nurs. 2001 January-February; 5(1): 5-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11899406&dopt=Abstract
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Receptor for hyaluronan-mediated motility and CD44 expressions in colon cancer assessed by quantitative analysis using real-time reverse transcriptase-polymerase chain reaction. Author(s): Yamada Y, Itano N, Narimatsu H, Kudo T, Hirohashi S, Ochiai A, Niimi A, Ueda M, Kimata K. Source: Jpn J Cancer Res. 1999 September; 90(9): 987-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10551329&dopt=Abstract
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Recognition of human colon cancer by T cells transduced with a chimeric receptor gene. Author(s): Daly T, Royal RE, Kershaw MH, Treisman J, Wang G, Li W, Herlyn D, Eshhar Z, Hwu P. Source: Cancer Gene Ther. 2000 February; 7(2): 284-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10770638&dopt=Abstract
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Reconstruction of urinary tract utilizing transverse colon conduit for a cystectomized patient with post-ureterocutaneostomy complications and sigmoid colon cancer. Author(s): Morita K, Ishikawa R, Enami N, Kashiwagi A, Murayama M, Yamagami H, Kimura J, Miura M. Source: Hokkaido Igaku Zasshi. 2001 July; 76(4): 199-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11523111&dopt=Abstract
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Reduced expression and altered subcellular localization of the cyclin-dependent kinase inhibitor p27(Kip1) in human colon cancer. Author(s): Sgambato A, Ratto C, Faraglia B, Merico M, Ardito R, Schinzari G, Romano G, Cittadini AR. Source: Mol Carcinog. 1999 November; 26(3): 172-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10559792&dopt=Abstract
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Reduced expression of the metastasis suppressor gene KAI1 in advanced colon cancer and its metastases. Author(s): Maurer CA, Graber HU, Friess H, Beyermann B, Willi D, Netzer P, Zimmermann A, Buchler MW. Source: Surgery. 1999 November; 126(5): 869-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10568187&dopt=Abstract
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Reevaluation of colon cancer staging--stricture presence reflects advanced disease? Author(s): Koch TR. Source: Am J Gastroenterol. 2002 March; 97(3): 759. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11922577&dopt=Abstract
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Regional delivery and selective expression of a high-activity yeast cytosine deaminase in an intrahepatic colon cancer model. Author(s): Zhang M, Li S, Nyati MK, DeRemer S, Parsels J, Rehemtulla A, Ensminger WD, Lawrence TS. Source: Cancer Res. 2003 February 1; 63(3): 658-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566311&dopt=Abstract
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Regression analysis with multiplicative and time-varying additive regression coefficients with examples from breast and colon cancer. Author(s): Zahl PH. Source: Stat Med. 2003 April 15; 22(7): 1113-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652557&dopt=Abstract
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Regression of colon cancer and induction of antitumor immunity by intratumoral injection of adenovirus expressing interleukin-12. Author(s): Mazzolini G, Qian C, Xie X, Sun Y, Lasarte JJ, Drozdzik M, Prieto J. Source: Cancer Gene Ther. 1999 November-December; 6(6): 514-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10608348&dopt=Abstract
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Regrowth of 5-fluorouracil-treated human colon cancer cells is prevented by the combination of interferon gamma, indomethacin, and phenylbutyrate. Author(s): Huang Y, Horvath CM, Waxman S. Source: Cancer Res. 2000 June 15; 60(12): 3200-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10866311&dopt=Abstract
278 Colon Cancer
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Regulation of interleukin-6 gene expression by pro-inflammatory cytokines in a colon cancer cell line. Author(s): Legrand-Poels S, Schoonbroodt S, Piette J. Source: Biochem J. 2000 August 1; 349 Pt 3: 765-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10903137&dopt=Abstract
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Regulation of TRAIL expression by the phosphatidylinositol 3-kinase/Akt/GSK-3 pathway in human colon cancer cells. Author(s): Wang Q, Wang X, Hernandez A, Hellmich MR, Gatalica Z, Evers BM. Source: J Biol Chem. 2002 September 27; 277(39): 36602-10. Epub 2002 July 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140294&dopt=Abstract
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Regulation of vascular endothelial growth factor expression in human colon cancer by insulin-like growth factor-I. Author(s): Akagi Y, Liu W, Zebrowski B, Xie K, Ellis LM. Source: Cancer Res. 1998 September 1; 58(17): 4008-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9731515&dopt=Abstract
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Regulation of vascular endothelial growth factor expression in human colon cancer by interleukin-1beta. Author(s): Akagi Y, Liu W, Xie K, Zebrowski B, Shaheen RM, Ellis LM. Source: Br J Cancer. 1999 July; 80(10): 1506-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10408390&dopt=Abstract
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Regulatory effect of interleukin-4 and interleukin-13 on colon cancer cell adhesion. Author(s): Kanai T, Watanabe M, Hayashi A, Nakazawa A, Yajima T, Okazawa A, Yamazaki M, Ishii H, Hibi T. Source: Br J Cancer. 2000 May; 82(10): 1717-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10817509&dopt=Abstract
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Regulatory network of mitomycin C action in human colon cancer cells. Author(s): Suzuki K, Yamamoto W, Park JS, Hanaoka H, Okamoto R, Kirihara Y, Yorishima T, Okamura T, Kumazaki T, Nishiyama M. Source: Jpn J Cancer Res. 1999 May; 90(5): 571-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10391098&dopt=Abstract
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Relation between colitis and colon cancer. Author(s): Shanahan F. Source: Lancet. 2001 January 27; 357(9252): 246-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11214121&dopt=Abstract
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Relationship between endogenous colony stimulating factors and apoptosis in human colon cancer cells: role of cyclo-oxygenase inhibitors. Author(s): Calatayud S, Warner TD, Breese EJ, Mitchell JA. Source: Br J Pharmacol. 2001 November; 134(6): 1237-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704643&dopt=Abstract
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Relationship of the interleukin-1 system with neuroendocrine and exocrine markers in human colon cancer cell lines. Author(s): Abdul M, Hoosein N. Source: Cytokine. 2002 April 21; 18(2): 86-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12096923&dopt=Abstract
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Relative therapeutic efficacy of (125)I- and (131)I-labeled monoclonal antibody A33 in a human colon cancer xenograft. Author(s): Barendswaard EC, Humm JL, O'Donoghue JA, Sgouros G, Finn RD, Scott AM, Larson SM, Welt S. Source: J Nucl Med. 2001 August; 42(8): 1251-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11483688&dopt=Abstract
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Replicating parvoviruses that target colon cancer cells. Author(s): Malerba M, Daeffler L, Rommelaere J, Iggo RD. Source: J Virol. 2003 June; 77(12): 6683-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767988&dopt=Abstract
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Reproductive hormones and cancer: ovarian and colon cancer. Author(s): Burkman RT. Source: Obstet Gynecol Clin North Am. 2002 September; 29(3): 527-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353672&dopt=Abstract
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Researchers suggest relaxation of food guidelines before colon cancer test. Author(s): Frankish H. Source: Lancet. 2001 August 25; 358(9282): 645. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11530163&dopt=Abstract
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Resection with external beam and intraoperative radiotherapy for recurrent colon cancer. Author(s): Pezner RD, Chu DZ, Wagman LD, Vora N, Wong JY, Shibata SI. Source: Arch Surg. 1999 January; 134(1): 63-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9927133&dopt=Abstract
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Resistance factors in colon cancer tissue and the adjacent normal colon tissue: glutathione S-transferases alpha and pi, glutathione and aldehyde dehydrogenase. Author(s): Hengstler JG, Bottger T, Tanner B, Dietrich B, Henrich M, Knapstein PG, Junginger T, Oesch F. Source: Cancer Lett. 1998 June 5; 128(1): 105-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9652800&dopt=Abstract
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Resistance of colon cancer cells to long-term 5-fluorouracil exposure is correlated to the relative level of Bcl-2 and Bcl-X(L) in addition to Bax and p53 status. Author(s): Violette S, Poulain L, Dussaulx E, Pepin D, Faussat AM, Chambaz J, Lacorte JM, Staedel C, Lesuffleur T. Source: Int J Cancer. 2002 April 1; 98(4): 498-504. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920608&dopt=Abstract
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Resistance to apoptosis is increased during metastatic dissemination of colon cancer. Author(s): Oliver L, Cordel S, Barbieux I, LeCabellec MT, Meflah K, Gregoire M, Vallette FM. Source: Clin Exp Metastasis. 2002; 19(2): 175-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11964082&dopt=Abstract
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Results from National Surgical Adjuvant Breast and Bowel project colon cancer trials. Author(s): Douglass HO Jr. Source: J Clin Oncol. 2000 January; 18(1): 235. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10623716&dopt=Abstract
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Results of laparoscopic vs open resections for colon cancer in patients with a minimum follow-up of 3 years. Author(s): Feliciotti F, Paganini AM, Guerrieri M, Sanctis A, Campagnacci R, Lezoche E. Source: Surg Endosc. 2002 August; 16(8): 1158-61. Epub 2002 May 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11984684&dopt=Abstract
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Retinoic acids reduce matrilysin (matrix metalloproteinase 7) and inhibit tumor cell invasion in human colon cancer. Author(s): Adachi Y, Itoh F, Yamamoto H, Iku S, Matsuno K, Arimura Y, Imai K. Source: Tumour Biol. 2001 July-August; 22(4): 247-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11399950&dopt=Abstract
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Review article: COX-2, prostanoids and colon cancer. Author(s): Ota S, Bamba H, Kato A, Kawamoto C, Yoshida Y, Fujiwara K. Source: Aliment Pharmacol Ther. 2002 April; 16 Suppl 2: 102-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966530&dopt=Abstract
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Review article: cyclooxygenase--a target for colon cancer prevention. Author(s): Dubois RN. Source: Aliment Pharmacol Ther. 2000 April; 14 Suppl 1: 64-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10807405&dopt=Abstract
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Ribozyme-mediated inactivation of mutant K-ras oncogene in a colon cancer cell line. Author(s): Tokunaga T, Tsuchida T, Kijima H, Okamoto K, Oshika Y, Sawa N, Ohnishi Y, Yamazaki H, Miura S, Ueyama Y, Nakamura M. Source: Br J Cancer. 2000 September; 83(6): 833-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10952790&dopt=Abstract
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Risk factors for morbidity and mortality after colectomy for colon cancer. Author(s): Audisio RA. Source: Tech Coloproctol. 2001 December; 5(3): 177-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892032&dopt=Abstract
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Risk factors for morbidity and mortality after colectomy for colon cancer. Author(s): Longo WE, Virgo KS, Johnson FE, Oprian CA, Vernava AM, Wade TP, Phelan MA, Henderson WG, Daley J, Khuri SF. Source: Dis Colon Rectum. 2000 January; 43(1): 83-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10813129&dopt=Abstract
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Risk of colon cancer associated with a family history of cancer or colorectal polyps: the diet, activity, and reproduction in colon cancer study. Author(s): Kerber RA, Slattery ML, Potter JD, Caan BJ, Edwards SL. Source: Int J Cancer. 1998 October 5; 78(2): 157-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9754645&dopt=Abstract
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Role of biological markers in the clinical outcome of colon cancer. Author(s): Nanni O, Volpi A, Frassineti GL, De Paola F, Granato AM, Dubini A, Zoli W, Scarpi E, Turci D, Oliverio G, Gambi A, Amadori D. Source: Br J Cancer. 2002 October 7; 87(8): 868-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12373601&dopt=Abstract
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Role of carcinoembryonic antigen in the progression of colon cancer cells that express carbohydrate antigen. Author(s): Minami S, Furui J, Kanematsu T. Source: Cancer Res. 2001 March 15; 61(6): 2732-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11289155&dopt=Abstract
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Role of caspase-3 in apoptosis of colon cancer cells induced by nonsteroidal antiinflammatory drugs. Author(s): Kim WH, Yeo M, Kim MS, Chun SB, Shin EC, Park JH, Park IS. Source: Int J Colorectal Dis. 2000 April; 15(2): 105-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10855553&dopt=Abstract
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Role of coactivators and corepressors in the induction of the RARbeta gene in human colon cancer cells. Author(s): Lee MO, Kang HJ. Source: Biol Pharm Bull. 2002 October; 25(10): 1298-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12392082&dopt=Abstract
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Role of dietary fiber in colon cancer: an overview. Author(s): Reddy BS. Source: Am J Med. 1999 January 25; 106(1A): 16S-19S; Discussion 50S-51S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10089109&dopt=Abstract
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Role of nuclear factor-kappa B in colon cancer cell apoptosis mediated by aminopyropheophorbide photosensitization. Author(s): Matroule JY, Hellin AC, Morliere P, Fabiano AS, Santus R, Merville MP, Piette J. Source: Photochem Photobiol. 1999 October; 70(4): 540-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10546550&dopt=Abstract
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Role of retinoblastoma protein and E2F-1 transcription factor in the acquisition of 5fluorouracil resistance by colon cancer cells. Author(s): Obama K, Kanai M, Kawai Y, Fukushima M, Takabayashi A. Source: Int J Oncol. 2002 August; 21(2): 309-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12118326&dopt=Abstract
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Role of yoghurt in the prevention of colon cancer. Author(s): Perdigon G, de Moreno de LeBlanc A, Valdez J, Rachid M. Source: Eur J Clin Nutr. 2002 August; 56 Suppl 3: S65-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142967&dopt=Abstract
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RPR-115135, a farnesyltransferase inhibitor, increases 5-FU- cytotoxicity in ten human colon cancer cell lines: role of p53. Author(s): Russo P, Malacarne D, Falugi C, Trombino S, O'Connor PM. Source: Int J Cancer. 2002 July 20; 100(3): 266-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115540&dopt=Abstract
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Rye bread improves bowel function and decreases the concentrations of some compounds that are putative colon cancer risk markers in middle-aged women and men. Author(s): Grasten SM, Juntunen KS, Poutanen KS, Gylling HK, Miettinen TA, Mykkanen HM. Source: J Nutr. 2000 September; 130(9): 2215-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10958815&dopt=Abstract
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Schedule-dependent interaction between raltitrexed and 5-fluorouracil in human colon cancer cell lines in vitro. Author(s): Kano Y, Akutsu M, Suzuki K, Yazawa Y, Tsunoda S, Furukawa Y. Source: Oncol Res. 2000; 12(3): 137-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11216672&dopt=Abstract
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Screening for colon cancer and evaluation of chemoprevention with coxibs. Author(s): Rex DK. Source: J Pain Symptom Manage. 2002 April; 23(4 Suppl): S41-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992750&dopt=Abstract
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Screening for colon cancer--can we afford colonoscopy? Author(s): Detsky AS. Source: N Engl J Med. 2001 August 23; 345(8): 607-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11529216&dopt=Abstract
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Screening for osteoporosis and colon cancer under Medicare. Author(s): Adler GS, Shatto A. Source: Health Care Financ Rev. 2002 Summer; 23(4): 189-200. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500479&dopt=Abstract
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Selective induction of colon cancer cell apoptosis by 5-fluorouracil in humans. Author(s): Rigas A, Dervenis C, Giannakou N, Kozoni V, Shiff SJ, Rigas B. Source: Cancer Invest. 2002; 20(5-6): 657-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197221&dopt=Abstract
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Selective targeting to the hyperactive beta-catenin/T-cell factor pathway in colon cancer cells. Author(s): Chen RH, McCormick F. Source: Cancer Res. 2001 June 1; 61(11): 4445-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11389074&dopt=Abstract
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Selenomethionine inhibits growth and suppresses cyclooxygenase-2 (COX-2) protein expression in human colon cancer cell lines. Author(s): Baines A, Taylor-Parker M, Goulet AC, Renaud C, Gerner EW, Nelson MA. Source: Cancer Biol Ther. 2002 July-August; 1(4): 370-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432249&dopt=Abstract
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Sensitization of human colon cancer cells to TRAIL-mediated apoptosis. Author(s): Hernandez A, Wang QD, Schwartz SA, Evers BM. Source: J Gastrointest Surg. 2001 January-February; 5(1): 56-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11309649&dopt=Abstract
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Serological analysis of human anti-human antibody responses in colon cancer patients treated with repeated doses of humanized monoclonal antibody A33. Author(s): Ritter G, Cohen LS, Williams C Jr, Richards EC, Old LJ, Welt S. Source: Cancer Res. 2001 September 15; 61(18): 6851-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11559561&dopt=Abstract
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Serrated adenoma developing into advanced colon cancer in 2 years. Author(s): Yamauchi T, Watanabe M, Hasegawa H, Yamamoto S, Endo T, Kabeshima Y, Yorozuya K, Yamamoto K, Kitajima M. Source: J Gastroenterol. 2002; 37(6): 467-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12108682&dopt=Abstract
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Short chain fatty acids and colon cancer. Author(s): Augenlicht LH, Mariadason JM, Wilson A, Arango D, Yang W, Heerdt BG, Velcich A. Source: J Nutr. 2002 December; 132(12): 3804S-3808S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468628&dopt=Abstract
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Short-chain fatty acids inhibit invasive human colon cancer by modulating uPA, TIMP-1, TIMP-2, mutant p53, Bcl-2, Bax, p21 and PCNA protein expression in an in vitro cell culture model. Author(s): Emenaker NJ, Calaf GM, Cox D, Basson MD, Qureshi N. Source: J Nutr. 2001 November; 131(11 Suppl): 3041S-6S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694645&dopt=Abstract
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Short-term quality-of-life outcomes following laparoscopic-assisted colectomy vs open colectomy for colon cancer: a randomized trial. Author(s): Weeks JC, Nelson H, Gelber S, Sargent D, Schroeder G; Clinical Outcomes of Surgical Therapy (COST) Study Group. Source: Jama. 2002 January 16; 287(3): 321-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11790211&dopt=Abstract
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Sigmoid colon cancer during pregnancy. Author(s): Vitoratos N, Salamalekis E, Makrakis E, Creatsas G. Source: Eur J Obstet Gynecol Reprod Biol. 2002 August 5; 104(1): 70-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12128267&dopt=Abstract
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Silence of chromosomal amplifications in colon cancer. Author(s): Platzer P, Upender MB, Wilson K, Willis J, Lutterbaugh J, Nosrati A, Willson JK, Mack D, Ried T, Markowitz S. Source: Cancer Res. 2002 February 15; 62(4): 1134-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11861394&dopt=Abstract
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Single alteration of p53 or E-cadherin genes can alter the surgical resection benefit in an experimental model of colon cancer. Author(s): Pocard M, Debruyne P, Bras-Goncalves R, Mareel M, Dutrillaux B, Poupon MF. Source: Dis Colon Rectum. 2001 August; 44(8): 1106-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11535849&dopt=Abstract
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Skip metastases in colon cancer: assessment by lymph node mapping using molecular detection. Author(s): Merrie AE, Phillips LV, Yun K, McCall JL. Source: Surgery. 2001 June; 129(6): 684-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11391366&dopt=Abstract
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Sodium butyrate-induced differentiation of human LIM2537 colon cancer cells decreases GSK-3beta activity and increases levels of both membrane-bound and Apc/axin/GSK-3beta complex-associated pools of beta-catenin. Author(s): Vincan E, Leet CS, Reyes NI, Dilley RJ, Thomas RJ, Phillips WA. Source: Oncol Res. 2000; 12(4): 193-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11341469&dopt=Abstract
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Soft-tissue images. Portal vein thrombosis and gas formation: unusual presentation of colon cancer. Author(s): Hong D, Lovrics P. Source: Can J Surg. 2001 April; 44(2): 90-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11308242&dopt=Abstract
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Solitary cerebellar metastasis as a presentation for colon cancer: a case report and review of the literature. Author(s): DeWitt J, Lippman HR, Wassef W. Source: Dig Dis Sci. 2001 June; 46(6): 1163-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11414288&dopt=Abstract
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Soluble Fas antigen in the serum of patients with colon cancer. Author(s): Kushlinskii NE, Britvin TA, Abbasova SG, Perevoshchikov AG, Prorokov VV, Kostanyan IA, Knysh VI, Lipkin VM. Source: Bull Exp Biol Med. 2001 April; 131(4): 361-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550026&dopt=Abstract
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Soluble Fas ligand released by colon adenocarcinoma cells induces host lymphocyte apoptosis: an active mode of immune evasion in colon cancer. Author(s): Song E, Chen J, Ouyang N, Su F, Wang M, Heemann U. Source: Br J Cancer. 2001 September 28; 85(7): 1047-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11592778&dopt=Abstract
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Specific inhibition of cyclooxygenase-2 (COX-2) expression by dietary curcumin in HT-29 human colon cancer cells. Author(s): Goel A, Boland CR, Chauhan DP. Source: Cancer Lett. 2001 October 30; 172(2): 111-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11566484&dopt=Abstract
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Spectral karyotype analysis of colon cancer cell lines of the tumor suppressor and mutator pathway. Author(s): Melcher R, Koehler S, Steinlein C, Schmid M, Mueller CR, Luehrs H, Menzel T, Scheppach W, Moerk H, Scheurlen M, Koehrle J, Al-Taie O. Source: Cytogenet Genome Res. 2002; 98(1): 22-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584437&dopt=Abstract
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Spectrum of matrix metalloproteinase expression in primary and metastatic colon cancer: relationship to the tissue inhibitors of metalloproteinases and membrane type-1-matrix metalloproteinase. Author(s): Collins HM, Morris TM, Watson SA. Source: Br J Cancer. 2001 June 15; 84(12): 1664-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401321&dopt=Abstract
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Sphingoid bases and ceramide induce apoptosis in HT-29 and HCT-116 human colon cancer cells. Author(s): Ahn EH, Schroeder JJ. Source: Exp Biol Med (Maywood). 2002 May; 227(5): 345-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11976405&dopt=Abstract
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Sphingomyelin protects against apoptosis and hyperproliferation induced by deoxycholate: potential implications for colon cancer. Author(s): Moschetta A, Portincasa P, van Erpecum KJ, Debellis L, VanbergeHenegouwen GP, Palasciano G. Source: Dig Dis Sci. 2003 June; 48(6): 1094-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822868&dopt=Abstract
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Src-induced de-regulation of E-cadherin in colon cancer cells requires integrin signalling. Author(s): Avizienyte E, Wyke AW, Jones RJ, McLean GW, Westhoff MA, Brunton VG, Frame MC. Source: Nat Cell Biol. 2002 August; 4(8): 632-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12134161&dopt=Abstract
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Staphylococcus cohnii septicaemia in a patient with colon cancer. Author(s): Basaglia G, Moras L, Bearz A, Scalone S, Paoli PD. Source: J Med Microbiol. 2003 January; 52(Pt 1): 101-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488572&dopt=Abstract
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Stimulation of Cdx1 by oncogenic beta-catenin/Tcf4 in colon cancer cells; opposite effect of the CDX2 homeoprotein. Author(s): Domon-Dell C, Freund JN. Source: Febs Lett. 2002 May 8; 518(1-3): 83-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11997022&dopt=Abstract
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Stimulation of the intestinal Cdx2 homeobox gene by butyrate in colon cancer cells. Author(s): Domon-Dell C, Wang Q, Kim S, Kedinger M, Evers BM, Freund JN. Source: Gut. 2002 April; 50(4): 525-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889074&dopt=Abstract
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Studies move closer to genetic test to detect colon cancer. Author(s): Clark G. Source: J Natl Cancer Inst. 2001 June 6; 93(11): 802. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11390524&dopt=Abstract
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Studies on human colon cancer gene APC by targeted expression in Drosophila. Author(s): Bhandari P, Shashidhara LS. Source: Oncogene. 2001 October 18; 20(47): 6871-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11687966&dopt=Abstract
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Study on the secondary structure of protein in amide I band from human colon cancer tissue by Fourier-transform infrared spectroscopy. Author(s): Chen YJ, Hsieh YW, Cheng YD, Liao CC. Source: Chang Gung Med J. 2001 September; 24(9): 541-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11725623&dopt=Abstract
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Subserosal invading colon cancer with rare invasive form. Author(s): Tadokoro T, Tamura S, Yokoyama Y, Morita T, Higashidani Y, Onishi S, Moriki T. Source: J Gastroenterol. 2002; 37(8): 676-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12203088&dopt=Abstract
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Successful removal of solitary intramedullary spinal cord metastasis from colon cancer. Author(s): Ogino M, Ueda R, Nakatsukasa M, Murase I. Source: Clin Neurol Neurosurg. 2002 May; 104(2): 152-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932047&dopt=Abstract
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Successful treatment for the IVC syndrome due to recurrence of colon cancer-chemotherapy in combination with the use of the expandable metallic stent placement. Author(s): Sato T, Itoh M, Ohta N, Motoyoshi A, Saito Z, Umezaki M. Source: Hepatogastroenterology. 2001 July-August; 48(40): 1048-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11490797&dopt=Abstract
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Sulindac sulfide inhibits epidermal growth factor-induced phosphorylation of extracellular-regulated kinase 1/2 and Bad in human colon cancer cells. Author(s): Rice PL, Washington M, Schleman S, Beard KS, Driggers LJ, Ahnen DJ. Source: Cancer Res. 2003 February 1; 63(3): 616-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566304&dopt=Abstract
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Suppression of a sialyltransferase by antisense DNA reduces invasiveness of human colon cancer cells in vitro. Author(s): Zhu Y, Srivatana U, Ullah A, Gagneja H, Berenson CS, Lance P. Source: Biochim Biophys Acta. 2001 May 31; 1536(2-3): 148-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11406350&dopt=Abstract
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Suppression of angiogenesis and therapy of human colon cancer liver metastasis by systemic administration of interferon-alpha. Author(s): Ozawa S, Shinohara H, Kanayama HO, Bruns CJ, Bucana CD, Ellis LM, Davis DW, Fidler IJ. Source: Neoplasia. 2001 March-April; 3(2): 154-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11420751&dopt=Abstract
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Suppression of beta-catenin inhibits the neoplastic growth of APC-mutant colon cancer cells. Author(s): Roh H, Green DW, Boswell CB, Pippin JA, Drebin JA. Source: Cancer Res. 2001 September 1; 61(17): 6563-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522655&dopt=Abstract
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Suppression of promoter-dependent transcriptional activity of inducible nitric oxide synthase by sodium butyrate in colon cancer cells. Author(s): Sasahara Y, Mutoh M, Takahashi M, Fukuda K, Tanaka N, Sugimura T, Wakabayashi K. Source: Cancer Lett. 2002 March 28; 177(2): 155-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11825662&dopt=Abstract
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Suppression of serum-induced c-jun expression by activated Ki-ras in human colon cancer cells. Author(s): Furuse M, Shirasawa S, Okumura K, Ohmori M, Sasazuki T. Source: Jpn J Hum Genet. 1997 September; 42(3): 409-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503187&dopt=Abstract
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Suppression of spontaneous and hydrogen peroxide-induced mutagenesis by the antioxidant ascorbate in mismatch repair-deficient human colon cancer cells. Author(s): Glaab WE, Hill RB, Skopek TR. Source: Carcinogenesis. 2001 October; 22(10): 1709-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11577013&dopt=Abstract
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Surgeon volume compared to hospital volume as a predictor of outcome following primary colon cancer resection. Author(s): Schrag D, Panageas KS, Riedel E, Hsieh L, Bach PB, Guillem JG, Begg CB. Source: J Surg Oncol. 2003 June; 83(2): 68-78; Discussion 78-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772198&dopt=Abstract
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Surgery for colon cancer. Author(s): Hohenberger W, Reingruber B, Merkel S. Source: Scand J Surg. 2003; 92(1): 45-52. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705550&dopt=Abstract
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Surgical evolution: clinical practice catching up to tumor biology in breast and colon cancer. Author(s): Lanzafame RJ. Source: J Clin Laser Med Surg. 2000 August; 18(4): 171-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11573508&dopt=Abstract
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Surgical management of colon cancer. Author(s): Colquhoun PH, Wexner SD. Source: Curr Gastroenterol Rep. 2002 October; 4(5): 414-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12228044&dopt=Abstract
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Surgical technique and survival in patients having a curative resection for colon cancer. Author(s): Bokey EL, Chapuis PH, Dent OF, Mander BJ, Bissett IP, Newland RC. Source: Dis Colon Rectum. 2003 July; 46(7): 860-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847357&dopt=Abstract
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Surgical treatment of colon cancer: does sentinel node technology have a role? Author(s): Fazio VW, Kiran RP. Source: Adv Surg. 2003; 37: 71-94. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953628&dopt=Abstract
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Surgical treatment of hepatic and pulmonary metastases from colon cancer. Author(s): Headrick JR, Miller DL, Nagorney DM, Allen MS, Deschamps C, Trastek VF, Pairolero PC. Source: Ann Thorac Surg. 2001 March; 71(3): 975-9; Discussion 979-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11269484&dopt=Abstract
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Survival associated with 5-fluorouracil-based adjuvant chemotherapy among elderly patients with node-positive colon cancer. Author(s): Sundararajan V, Mitra N, Jacobson JS, Grann VR, Heitjan DF, Neugut AI. Source: Ann Intern Med. 2002 March 5; 136(5): 349-57. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11874307&dopt=Abstract
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Synergistic antitumor effect of TRAIL and doxorubicin on colon cancer cell line SW480. Author(s): Xu LH, Deng CS, Zhu YQ, Liu SQ, Liu DZ. Source: World J Gastroenterol. 2003 June; 9(6): 1241-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800232&dopt=Abstract
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Synthesis of disialyl Lewis a (Le(a)) structure in colon cancer cell lines by a sialyltransferase, ST6GalNAc VI, responsible for the synthesis of alpha-series gangliosides. Author(s): Tsuchida A, Okajima T, Furukawa K, Ando T, Ishida H, Yoshida A, Nakamura Y, Kannagi R, Kiso M, Furukawa K. Source: J Biol Chem. 2003 June 20; 278(25): 22787-94. Epub 2003 March 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668675&dopt=Abstract
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Synthetic low-calcaemic vitamin D(3) analogues inhibit secretion of insulin-like growth factor II and stimulate production of insulin-like growth factor-binding protein-6 in conjunction with growth suppression of HT-29 colon cancer cells. Author(s): Oh YS, Kim EJ, Schaffer BS, Kang YH, Binderup L, MacDonald RG, Park JH. Source: Mol Cell Endocrinol. 2001 October 25; 183(1-2): 141-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11604234&dopt=Abstract
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Target disruption of the mutant beta-catenin gene in colon cancer cell line HCT116: preservation of its malignant phenotype. Author(s): Sekine S, Shibata T, Sakamoto M, Hirohashi S. Source: Oncogene. 2002 August 29; 21(38): 5906-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12185590&dopt=Abstract
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Tart cherry anthocyanins inhibit tumor development in Apc(Min) mice and reduce proliferation of human colon cancer cells. Author(s): Kang SY, Seeram NP, Nair MG, Bourquin LD. Source: Cancer Lett. 2003 May 8; 194(1): 13-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706854&dopt=Abstract
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Tea consumption and the reduced risk of colon cancer -- results from a national prospective cohort study. Author(s): Su LJ, Arab L. Source: Public Health Nutr. 2002 June; 5(3): 419-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003653&dopt=Abstract
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Thalidomide suppresses the interleukin 1beta-induced NFkappaB signaling pathway in colon cancer cells. Author(s): Jin SH, Kim TI, Han DS, Shin SK, Kim WH. Source: Ann N Y Acad Sci. 2002 November; 973: 414-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485902&dopt=Abstract
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The African way of life and colon cancer risk. Author(s): O'Keefe SJ. Source: Am J Gastroenterol. 2001 November; 96(11): 3220-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11721790&dopt=Abstract
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The angiogenic switch of human colon cancer occurs simultaneous to initiation of invasion. Author(s): Takahashi Y, Ellis LM, Mai M. Source: Oncol Rep. 2003 January-February; 10(1): 9-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12469136&dopt=Abstract
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The Canadian Association of Gastroenterology position on colon cancer screening. Author(s): Leddin D. Source: Can J Gastroenterol. 2003 February; 17(2): 133-4. English, French. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605254&dopt=Abstract
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The colon cancer burden of genetically defined hereditary nonpolyposis colon cancer. Author(s): Samowitz WS, Curtin K, Lin HH, Robertson MA, Schaffer D, Nichols M, Gruenthal K, Leppert MF, Slattery ML. Source: Gastroenterology. 2001 October; 121(4): 830-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11606497&dopt=Abstract
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The effects of acetylsalicylic acid on proliferation, apoptosis, and invasion of cyclooxygenase-2 negative colon cancer cells. Author(s): Yu HG, Huang JA, Yang YN, Huang H, Luo HS, Yu JP, Meier JJ, Schrader H, Bastian A, Schmidt WE, Schmitz F. Source: Eur J Clin Invest. 2002 November; 32(11): 838-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12423325&dopt=Abstract
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The effects of short-chain fatty acids on human colon cancer cell phenotype are associated with histone hyperacetylation. Author(s): Hinnebusch BF, Meng S, Wu JT, Archer SY, Hodin RA. Source: J Nutr. 2002 May; 132(5): 1012-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11983830&dopt=Abstract
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The expression of human FUT1 in HT-29/M3 colon cancer cells instructs the glycosylation of MUC1 and MUC5AC apomucins. Author(s): Lopez-Ferrer A, de Bolos C. Source: Glycoconj J. 2002 January; 19(1): 13-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652076&dopt=Abstract
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The future of colon cancer prevention. Author(s): Umar A, Viner JL, Hawk ET. Source: Ann N Y Acad Sci. 2001 December; 952: 88-108. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11795446&dopt=Abstract
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The impact of a celebrity promotional campaign on the use of colon cancer screening: the Katie Couric effect. Author(s): Cram P, Fendrick AM, Inadomi J, Cowen ME, Carpenter D, Vijan S. Source: Arch Intern Med. 2003 July 14; 163(13): 1601-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860585&dopt=Abstract
Studies 293
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The importance of histopathological and clinical variables in predicting the evolution of colon cancer. Author(s): Diculescu M, Iacob R, Iacob S, Croitoru A, Becheanu G, Popeneciu V. Source: Rom J Gastroenterol. 2002 September; 11(3): 183-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368937&dopt=Abstract
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The in vitro and in vivo effects of 2-(4-morpholinyl)-8-phenyl-chromone (LY294002), a specific inhibitor of phosphatidylinositol 3'-kinase, in human colon cancer cells. Author(s): Semba S, Itoh N, Ito M, Harada M, Yamakawa M. Source: Clin Cancer Res. 2002 June; 8(6): 1957-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12060641&dopt=Abstract
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The incidence of positive peritoneal cytology in colon cancer: a prospective randomized blinded trial. Author(s): Lucha PA Jr, Ignacio R, Rowley D, Francis M. Source: Am Surg. 2002 November; 68(11): 1018-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455799&dopt=Abstract
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The influence of folate and multivitamin use on the familial risk of colon cancer in women. Author(s): Fuchs CS, Willett WC, Colditz GA, Hunter DJ, Stampfer MJ, Speizer FE, Giovannucci EL. Source: Cancer Epidemiol Biomarkers Prev. 2002 March; 11(3): 227-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11895870&dopt=Abstract
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The leukotriene receptor CysLT1 and 5-lipoxygenase are upregulated in colon cancer. Author(s): Nielsen CK, Ohd JF, Wikstrom K, Massoumi R, Paruchuri S, Juhas M, Sjolander A. Source: Adv Exp Med Biol. 2003; 525: 201-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751768&dopt=Abstract
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The Mayo Clinic experience with multimodality treatment of locally advanced or recurrent colon cancer. Author(s): Taylor WE, Donohue JH, Gunderson LL, Nelson H, Nagorney DM, Devine RM, Haddock MG, Larson DR, Rubin J, O'Connell MJ. Source: Ann Surg Oncol. 2002 March; 9(2): 177-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11888876&dopt=Abstract
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The mitochondrial apoptosis-inducing factor plays a role in E2F-1-induced apoptosis in human colon cancer cells. Author(s): Vorburger SA, Pataer A, Yoshida K, Liu Y, Lu X, Swisher SG, Hunt KK. Source: Ann Surg Oncol. 2003 April; 10(3): 314-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679318&dopt=Abstract
294 Colon Cancer
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The molecular and genetic basis of colon cancer. Author(s): Robbins DH, Itzkowitz SH. Source: Med Clin North Am. 2002 November; 86(6): 1467-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510461&dopt=Abstract
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The novel germline mutation of hMSH2 gene in a case of a colon cancer patient without family history. Author(s): Ishida H, Furukawa H, Tatsuta M, Masutani S, Imamura H, Shimizu J, Masuda N, Kawasaki T, Satomi T, Sugano K, Fukayama N, Tomita N. Source: Jpn J Clin Oncol. 2002 July; 32(7): 266-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12324578&dopt=Abstract
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The potential of 5-fluorocytosine/cytosine deaminase enzyme prodrug gene therapy in an intrahepatic colon cancer model. Author(s): Nyati MK, Symon Z, Kievit E, Dornfeld KJ, Rynkiewicz SD, Ross BD, Rehemtulla A, Lawrence TS. Source: Gene Ther. 2002 July; 9(13): 844-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12080378&dopt=Abstract
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The prognosis of T3N0 colon cancer is dependent on the number of lymph nodes examined. Author(s): Swanson RS, Compton CC, Stewart AK, Bland KI. Source: Ann Surg Oncol. 2003 January-February; 10(1): 65-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12513963&dopt=Abstract
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The role of mitogen-activated protein kinases and their relationship with NF-kappaB and PPARgamma in indomethacin-Induced apoptosis of colon cancer cells. Author(s): Kim TI, Jin SH, Kang EH, Shin SK, Choi KY, Kim WH. Source: Ann N Y Acad Sci. 2002 November; 973: 241-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485869&dopt=Abstract
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The role of NSAIDs in the prevention of colon cancer. Author(s): Rayyan Y, Williams J, Rigas B. Source: Cancer Invest. 2002; 20(7-8): 1002-11. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12449734&dopt=Abstract
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The role of PPARgamma in colon cancer: is it as simple as APC? Author(s): Peek RM Jr. Source: Gastroenterology. 2003 August; 125(2): 619-21. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891569&dopt=Abstract
Studies 295
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The role of the Deleted Colon Cancer (DCC) gene in colorectal and gastric cancer. Author(s): O'Boyle K. Source: Cancer Invest. 2003 June; 21(3): 484-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901294&dopt=Abstract
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The sentinel node biopsy and colon cancer revisited. Author(s): Warner EE, Evans SR. Source: Cancer J. 2002 November-December; 8(6): 435-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500850&dopt=Abstract
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The structural nature of chromosomal instability in colon cancer cells. Author(s): Ribas M, Masramon L, Aiza G, Capella G, Miro R, Peinado MA. Source: Faseb J. 2003 February; 17(2): 289-91. Epub 2002 December 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475895&dopt=Abstract
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The suppression of colon cancer cell growth in nude mice by targeting betacatenin/TCF pathway. Author(s): Kwong KY, Zou Y, Day CP, Hung MC. Source: Oncogene. 2002 November 28; 21(54): 8340-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447697&dopt=Abstract
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The use of minimal preparation computed tomography for the primary investigation of colon cancer in frail or elderly patients. Author(s): Robinson P, Burnett H, Nicholson DA. Source: Clin Radiol. 2002 May; 57(5): 389-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014937&dopt=Abstract
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The utility of routine preoperative computed tomography scanning in the management of veterans with colon cancer. Author(s): Barton JB, Langdale LA, Cummins JS, Stelzner M, Lynge DC, Mock CN, Nason KS, Billingsley KG. Source: Am J Surg. 2002 May; 183(5): 499-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034380&dopt=Abstract
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The variable effect on proliferation of a colon cancer cell line by the citrus fruit flavonoid Naringenin. Author(s): Frydoonfar HR, McGrath DR, Spigelman AD. Source: Colorectal Dis. 2003 March; 5(2): 149-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780904&dopt=Abstract
296 Colon Cancer
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Therapeutic strategy of emergency surgery for colon cancer in 71 patients over 70 years of age in Japan. Author(s): Tsugawa K, Koyanagi N, Hashizume M, Akahoshi K, Wada H, Ayukawa K, Tomikawa M, Sugimachi K. Source: Hepatogastroenterology. 2002 March-April; 49(44): 393-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11995459&dopt=Abstract
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Therapy-related erythroleukemia caused by the administration of UFT and mitomycin C in a patient with colon cancer. Author(s): Nakamori Y, Miyazaki M, Tominaga T, Taguchi A, Shinohara K. Source: Int J Clin Oncol. 2003 February; 8(1): 56-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601545&dopt=Abstract
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Thioredoxin reductase 1 expression in colon cancer: discrepancy between in vitro and in vivo findings. Author(s): Lechner S, Muller-Ladner U, Neumann E, Spottl T, Schlottmann K, Ruschoff J, Scholmerich J, Kullmann F. Source: Lab Invest. 2003 September; 83(9): 1321-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13679440&dopt=Abstract
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Thymidylate synthase expression in stage II and III colon cancer: a retrospective review. Author(s): Tomiak A, Vincent M, Earle CC, Johnston PG, Kocha W, Taylor M, Maroun J, Eidus L, Whiston F, Stitt L. Source: Am J Clin Oncol. 2001 December; 24(6): 597-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11801762&dopt=Abstract
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Thymidylate synthase inhibition triggers apoptosis via caspases-8 and -9 in both wild-type and mutant p53 colon cancer cell lines. Author(s): Backus HH, Wouters D, Ferreira CG, van Houten VM, Brakenhoff RH, Pinedo HM, Peters GJ. Source: Eur J Cancer. 2003 June; 39(9): 1310-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763222&dopt=Abstract
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Total levels of tissue inhibitor of metalloproteinases 1 in plasma yield high diagnostic sensitivity and specificity in patients with colon cancer. Author(s): Holten-Andersen MN, Christensen IJ, Nielsen HJ, Stephens RW, Jensen V, Nielsen OH, Sorensen S, Overgaard J, Lilja H, Harris A, Murphy G, Brunner N. Source: Clin Cancer Res. 2002 January; 8(1): 156-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11801553&dopt=Abstract
Studies 297
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Total N-nitroso compounds and their precursors in hot dogs and in the gastrointestinal tract and feces of rats and mice: possible etiologic agents for colon cancer. Author(s): Mirvish SS, Haorah J, Zhou L, Clapper ML, Harrison KL, Povey AC. Source: J Nutr. 2002 November; 132(11 Suppl): 3526S-3529S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421882&dopt=Abstract
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Trans-10,cis-12-conjugated linoleic acid inhibits Caco-2 colon cancer cell growth. Author(s): Kim EJ, Holthuizen PE, Park HS, Ha YL, Jung KC, Park JH. Source: Am J Physiol Gastrointest Liver Physiol. 2002 August; 283(2): G357-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12121883&dopt=Abstract
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Trans-fatty acids and colon cancer. Author(s): Slattery ML, Benson J, Ma KN, Schaffer D, Potter JD. Source: Nutr Cancer. 2001; 39(2): 170-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11759276&dopt=Abstract
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Tributyrin-induced differentiation promotes apoptosis of LS 174T colon cancer cells in vitro. Author(s): Schroder CP, Maurer HR. Source: Int J Oncol. 2002 January; 20(1): 195-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11743664&dopt=Abstract
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Tumor budding at the invasive margin can predict patients at high risk of recurrence after curative surgery for stage II, T3 colon cancer. Author(s): Tanaka M, Hashiguchi Y, Ueno H, Hase K, Mochizuki H. Source: Dis Colon Rectum. 2003 August; 46(8): 1054-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907899&dopt=Abstract
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Tumor microsatellite-instability status as a predictor of benefit from fluorouracilbased adjuvant chemotherapy for colon cancer. Author(s): Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, Hamilton SR, Laurent-Puig P, Gryfe R, Shepherd LE, Tu D, Redston M, Gallinger S. Source: N Engl J Med. 2003 July 17; 349(3): 247-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867608&dopt=Abstract
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Tumor necrosis factor-alpha induces apoptosis associated with poly(ADP-ribose) polymerase cleavage in HT-29 colon cancer cells. Author(s): Vaculova A, Hofmanova J, Soucek K, Kovarikova M, Kozubik A. Source: Anticancer Res. 2002 May-June; 22(3): 1635-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12168847&dopt=Abstract
298 Colon Cancer
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Two mismatch repair gene mutations found in a colon cancer patient--which one is pathogenic? Author(s): Kariola R, Otway R, Lonnqvist KE, Raevaara TE, Macrae F, Vos YJ, KohonenCorish M, Hofstra RM, Nystrom-Lahti M. Source: Hum Genet. 2003 February; 112(2): 105-9. Epub 2002 November 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522549&dopt=Abstract
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Two unusual sites of colon cancer metastases and a rare thyroid lymphoma. Case 1. Metastatic colon cancer to a multinodular goiter. Author(s): De Ridder M, Sermeus AB, Van de Steene J, Storme GA. Source: J Clin Oncol. 2001 August 1; 19(15): 3572-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11481365&dopt=Abstract
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Two unusual sites of colon cancer metastases and a rare thyroid lymphoma. Case 3. Primary T-cell lymphoma of the thyroid arising in a background of Hashimoto's thyroiditis. Author(s): Raftopoulos I, Vanuno D, Kouraklis G. Source: J Clin Oncol. 2001 August 1; 19(15): 3576-80. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11481367&dopt=Abstract
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UFT plus calcium folinate vs 5-FU plus calcium folinate in colon cancer. Author(s): Smith R, Wickerham DL, Wieand HS, Colangelo L, Mamounas EP. Source: Oncology (Huntingt). 1999 July; 13(7 Suppl 3): 44-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10442360&dopt=Abstract
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UFT/leucovorin vs 5-FU/leucovorin in colon cancer. Author(s): Smith RE, Lembersky BC, Wieand HS, Colangelo L, Mamounas EP. Source: Oncology (Huntingt). 2000 October; 14(10 Suppl 9): 24-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11098486&dopt=Abstract
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Ulcerative colitis and colon cancer: more controversy than clarity. Author(s): Snapper SB, Syngal S, Friedman LS. Source: Dig Dis. 1998 March-April; 16(2): 81-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9571373&dopt=Abstract
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Ulcerative colitis and colon cancer: strategies for cancer prevention. Author(s): Campbell S, Ghosh S. Source: Dig Dis. 2002; 20(1): 38-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145419&dopt=Abstract
Studies 299
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Ultrastaging of early colon cancer using lymphatic mapping and molecular analysis. Author(s): Bilchik AJ, Nora D, Tollenaar RA, van de Velde CJ, Wood T, Turner R, Morton DL, Hoon DS. Source: Eur J Cancer. 2002 May; 38(7): 977-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978523&dopt=Abstract
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Uncommon TGFBRI allele is not associated with increased susceptibility to colon cancer. Author(s): Samowitz WS, Curtin K, Leppert MF, Slattery ML. Source: Genes Chromosomes Cancer. 2001 December; 32(4): 381-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11746979&dopt=Abstract
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Underreporting of family history of colon cancer: correlates and implications. Author(s): Glanz K, Grove J, Le Marchand L, Gotay C. Source: Cancer Epidemiol Biomarkers Prev. 1999 July; 8(7): 635-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10428202&dopt=Abstract
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Upregulation of activin A gene by butyrate in human colon cancer cell lines. Author(s): Sonoyama K, Pholnukulkit P, Toyoda M, Rutatip S, Kasai T. Source: Am J Physiol Gastrointest Liver Physiol. 2003 June; 284(6): G989-95. Epub 2003 January 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540370&dopt=Abstract
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Upregulation of galectins-1 and -3 in human colon cancer and their role in regulating cell migration. Author(s): Hittelet A, Legendre H, Nagy N, Bronckart Y, Pector JC, Salmon I, Yeaton P, Gabius HJ, Kiss R, Camby I. Source: Int J Cancer. 2003 January 20; 103(3): 370-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12471620&dopt=Abstract
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Up-regulation of plasma membrane-associated ganglioside sialidase (Neu3) in human colon cancer and its involvement in apoptosis suppression. Author(s): Kakugawa Y, Wada T, Yamaguchi K, Yamanami H, Ouchi K, Sato I, Miyagi T. Source: Proc Natl Acad Sci U S A. 2002 August 6; 99(16): 10718-23. Epub 2002 July 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149448&dopt=Abstract
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Upregulation of vascular endothelial growth factor by hydrogen peroxide in human colon cancer. Author(s): Zhu JW, Yu BM, Ji YB, Zheng MH, Li DH. Source: World J Gastroenterol. 2002 February; 8(1): 153-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11833093&dopt=Abstract
300 Colon Cancer
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Uptake of long-circulating immunoliposomes, directed against colon adenocarcinoma cells, by liver metastases of colon cancer. Author(s): Kamps JA, Koning GA, Velinova MJ, Morselt HW, Wilkens M, Gorter A, Donga J, Scherphof GL. Source: J Drug Target. 2000; 8(4): 235-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11144234&dopt=Abstract
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Use of c-myb antisense oligonucleotides to increase the sensitivity of human colon cancer cells to cisplatin. Author(s): Funato T, Satou J, Kozawa K, Fujimaki S, Miura T, Kaku M. Source: Oncol Rep. 2001 July-August; 8(4): 807-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11410788&dopt=Abstract
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Use of guanylyl cyclase C for detecting micrometastases in lymph nodes of patients with colon cancer. Author(s): Waldman SA, Cagir B, Rakinic J, Fry RD, Goldstein SD, Isenberg G, Barber M, Biswas S, Minimo C, Palazzo J, Park PK, Weinberg D. Source: Dis Colon Rectum. 1998 March; 41(3): 310-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9514425&dopt=Abstract
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Vaginal metastasis of colon cancer. Author(s): Chagpar A, Kanthan SC. Source: Am Surg. 2001 February; 67(2): 171-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11243544&dopt=Abstract
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Validation of sentinel node mapping in patients with colon cancer. Author(s): Paramo JC, Summerall J, Poppiti R, Mesko TW. Source: Ann Surg Oncol. 2002 July; 9(6): 550-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12095970&dopt=Abstract
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Variants of the VDR gene and risk of colon cancer (United States). Author(s): Slatter ML, Yakumo K, Hoffman M, Neuhausen S. Source: Cancer Causes Control. 2001 May; 12(4): 359-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11456232&dopt=Abstract
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Variation over time of the effects of prognostic factors in a population-based study of colon cancer: comparison of statistical models. Author(s): Quantin C, Abrahamowicz M, Moreau T, Bartlett G, MacKenzie T, Tazi MA, Lalonde L, Faivre J. Source: Am J Epidemiol. 1999 December 1; 150(11): 1188-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10588079&dopt=Abstract
Studies 301
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Variations in the use of adjuvant chemotherapy for node-positive colon cancer in the elderly: a population-based study. Author(s): Sundararajan V, Grann VR, Jacobson JS, Ahsan H, Neugut AI. Source: Cancer J. 2001 May-June; 7(3): 213-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11419029&dopt=Abstract
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Various functions of PBMC from colon cancer patients are not decreased compared to healthy blood donors. Author(s): Afzelius P, Nielsen HJ. Source: Cancer Biother Radiopharm. 1997 April; 12(2): 73-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10851450&dopt=Abstract
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Vascular endothelial growth factor (VEGF) mRNA isoform expression pattern is correlated with liver metastasis and poor prognosis in colon cancer. Author(s): Tokunaga T, Oshika Y, Abe Y, Ozeki Y, Sadahiro S, Kijima H, Tsuchida T, Yamazaki H, Ueyama Y, Tamaoki N, Nakamura M. Source: Br J Cancer. 1998 March; 77(6): 998-1002. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9528847&dopt=Abstract
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Vascular endothelial growth factor and p53 expressions in liver and abdominal metastases from colon cancer. Author(s): Cascinu S, Graziano F, Catalano V, Barni S, Giordani P, Baldelli AM, Staccioli MP, Rossi C, Brenna A, Valenti A, Muretto P, Catalano G. Source: Tumour Biol. 2003 March-April; 24(2): 77-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853702&dopt=Abstract
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Vascular endothelial growth factor expression, S-phase fraction and thymidylate synthase quantitation in node-positive colon cancer: relationships with tumor recurrence and resistance to adjuvant chemotherapy. Author(s): Cascinu S, Graziano F, Valentini M, Catalano V, Giordani P, Staccioli MP, Rossi C, Baldelli AM, Grianti C, Muretto P, Catalano G. Source: Ann Oncol. 2001 February; 12(2): 239-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11300331&dopt=Abstract
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Vascular endothelial growth factor gene expression in colon cancer cells exposed to prostaglandin E2 is mediated by hypoxia-inducible factor 1. Author(s): Fukuda R, Kelly B, Semenza GL. Source: Cancer Res. 2003 May 1; 63(9): 2330-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727858&dopt=Abstract
302 Colon Cancer
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Vascular endothelial growth factor in human colon cancer: biology and therapeutic implications. Author(s): Ellis LM, Takahashi Y, Liu W, Shaheen RM. Source: Oncologist. 2000; 5 Suppl 1: 11-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10804085&dopt=Abstract
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Vegetables, cereals and colon cancer mortality: long-term trend in Japan. Author(s): Kono S, Ahn YO. Source: Eur J Cancer Prev. 2000 October; 9(5): 363-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11075890&dopt=Abstract
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Vicia faba agglutinin, the lectin present in broad beans, stimulates differentiation of undifferentiated colon cancer cells. Author(s): Jordinson M, El-Hariry I, Calnan D, Calam J, Pignatelli M. Source: Gut. 1999 May; 44(5): 709-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10205210&dopt=Abstract
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Videotape-based decision aid for colon cancer screening. Author(s): Harewood G. Source: Ann Intern Med. 2001 October 16; 135(8 Pt 1): 634-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11601937&dopt=Abstract
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Videotape-based decision aid for colon cancer screening. A randomized, controlled trial. Author(s): Pignone M, Harris R, Kinsinger L. Source: Ann Intern Med. 2000 November 21; 133(10): 761-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11085838&dopt=Abstract
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Virtual colonoscopy for colon cancer screening: further reflections on polyps and politics. Author(s): Ferrucci JT. Source: Ajr Am J Roentgenol. 2003 September; 181(3): 795-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933483&dopt=Abstract
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Vitamin E and colon cancer: is there an association? Author(s): Slattery ML, Edwards SL, Anderson K, Caan B. Source: Nutr Cancer. 1998; 30(3): 201-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9631491&dopt=Abstract
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Vitamine D derivatives convert colon cancer cells. Author(s): Burton A. Source: Lancet Oncol. 2001 October; 2(10): 593. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11902546&dopt=Abstract
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Voltage-gated potassium ion channels in colon cancer. Author(s): Abdul M, Hoosein N. Source: Oncol Rep. 2002 September-October; 9(5): 961-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12168055&dopt=Abstract
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Western diet, family history of colorectal cancer, NAT2, GSTM-1 and risk of colon cancer. Author(s): Slattery ML, Potter JD, Ma KN, Caan BJ, Leppert M, Samowitz W. Source: Cancer Causes Control. 2000 January; 11(1): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10680724&dopt=Abstract
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What is the most cost-effective screening regimen for colon cancer? Author(s): Griffith S, Kane KY. Source: J Fam Pract. 2001 January; 50(1): 13. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11195472&dopt=Abstract
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What is the optimal strategy for colon cancer surveillance in patients with ulcerative colitis? Author(s): Bauer WM, Lashner BA. Source: Cleve Clin J Med. 1999 May; 66(5): 273, 277. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10330779&dopt=Abstract
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When colon cancer runs in the family. Author(s): DeDecker L. Source: Mich Nurse. 2001 August; 74(7): 24, 31. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11987643&dopt=Abstract
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Which colon cancer screening test? A comparison of costs, effectiveness, and compliance. Author(s): Vijan S, Hwang EW, Hofer TP, Hayward RA. Source: Am J Med. 2001 December 1; 111(8): 593-601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11755501&dopt=Abstract
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Wild-type p53 protein potentiates cytotoxicity of therapeutic agents in human colon cancer cells. Author(s): Yang B, Eshleman JR, Berger NA, Markowitz SD. Source: Clin Cancer Res. 1996 October; 2(10): 1649-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9816112&dopt=Abstract
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Wilms' tumor gene (WT1) expression in lung cancer, colon cancer and glioblastoma cell lines compared to freshly isolated tumor specimens. Author(s): Menssen HD, Bertelmann E, Bartelt S, Schmidt RA, Pecher G, Schramm K, Thiel E. Source: J Cancer Res Clin Oncol. 2000 April; 126(4): 226-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10782896&dopt=Abstract
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Wingless-type frizzled protein receptor signaling and its putative role in human colon cancer. Author(s): Uthoff SM, Eichenberger MR, McAuliffe TL, Hamilton CJ, Galandiuk S. Source: Mol Carcinog. 2001 May; 31(1): 56-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11398198&dopt=Abstract
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CHAPTER 2. NUTRITION AND COLON CANCER Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and colon cancer.
Finding Nutrition Studies on Colon Cancer The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “colon cancer” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following is a typical result when searching for recently indexed consumer information on colon cancer: ·
How to prevent colon cancer: new research updates old theories. Source: Antinoro, L. Environmental-nutrition (USA). (January 1999). volume 22(1) page 1, 6. intestines neoplasms human nutrition research dietary fibres diet fats body weight folic acid calcium alcoholic beverages 0893-4452 Summary: intestin neoplasme nutrition humaine recherche fibre alimentaire regime alimentaire corps gras poids corporel acide folique calcium boisson alcoolisee
Additional consumer oriented references include: ·
1. Is colon cancer really linked to a daily diet of red meat. Source: Conning, D.M. B-N-F-Nutr-Bull-Br-Nutr-Found. London : The Foundation. May 1991. volume 16 (2) page 60-61. 0141-9684
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By the way, doctor...I've had small amounts of blood in my bowel movements from time to time for years. My doctor has done a pretty thorough evaluation and has ruled out colon cancer or anything serious: what I have is plain old hemorrhoids. I've heard of an operation using rubber bands that can get rid of them. Should I go ahead and have this procedure done? Source: Lee, T H Harv-Health-Lett. 2000 June; 25(8): 8 1052-1577
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Calcium and vitamin D intakes influence the risk of bowel cancer in men. Source: Nutrition-reviews (USA). (June 1985). volume 43(6) page 170-172. vitamin d carcinoma intestines calcium 0029-6643
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Clues to colon cancer. Source: Liebman, B. Nutr-Action-Health-Lett. Washington, D.C. : Center for Science in the Public Interest. March 1990. volume 17 (2) page 1, 5-7. 0199-5510
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Colon cancer and fibre: ! or. Source: Arens, U. BNF-nutr-bull. London : The British Nutrition Foundation. Spring 1999. volume 24 (86) page 4-7. 0141-9684
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Colon cancer prevention. Worth the trouble. Source: Anonymous Harv-Health-Lett. 1999 November; 25(1): 1-2 1052-1577
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Diet and colon cancer. Source: Orta, J. Nutr-M-D. Van Nuys, Calif. : The Journal. April 1989. volume 15 (4) page 1-2. 0732-0167
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Diet, bacteria and colonic cancer. Source: Douglas, L. Nutr-food-sci. Bradford, West Yorkshire, England : MCB University Press. 1999. (4/5) page 187-191. 0034-6659
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Dietary habits affect colon cancer risk. Source: Anonymous Health-News. 1998 August 15; 4(10): 5 1081-5880
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Effect of wheat fiber and vitamins C and E supplements on rectal polyps in patients at high risk for colon cancer. Source: Anonymous Nutr-Revolume 1990 May; 48(5): 218-20 0029-6643
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Epidemiology and mechanisms relating diet to risk of colorectal cancer. Source: Mathews, F. Nutr-res-rev. Cambridge [England]; New York : Cambridge University Press, c1988-. 1996. volume 9 page 197-239. 0954-4224
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Fiber and colon cancer: does the current evidence justify a preventive policy? Author(s): USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111. Source: Ausman, L M Nutr-Revolume 1993 February; 51(2): 57-63 0029-6643
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Fiber helps diabetes... but not colon cancer? Source: Anonymous Health-News. 2000 June; 6(6): 5 1081-5880
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Fish-oil supplementation reduces intestinal hyperproliferation in persons at risk for colon cancer. Source: Anonymous Nutr-Revolume 1993 August; 51(8): 241-3 0029-6643
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Folate, alcohol, methionine, and colon cancer risk: is there a unifying theme? Source: Anonymous Nutr-Revolume 1994 January; 52(1): 18-20 0029-6643
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Folic acid lowers colon cancer risk. Source: Anonymous Health-News. 2002 May; 8(5): 5 1081-5880
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Iron and colorectal cancer risk: human studies. Author(s): Department of Surgery, University of Illinois at Chicago, 60612, USA. Source: Nelson, R L Nutr-Revolume 2001 May; 59(5): 140-8 0029-6643
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Is meat involved in colon cancer. Source: Nestle, M. BNF-nutr-bull. London : The British Nutrition Foundation. Spring 1998. volume 23 (83) page 79-83. 0141-9684
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Preventing colon cancer. Screening and early detection save lives. Source: Hall, L L FDA-Consum. 2000 Nov-December; 34(6): 14-8 0362-1332
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Reducing colon cancer risk. Source: Anonymous Health-News. 1998 October 25; 4(13): 7 1081-5880
The following information is typical of that found when using the “Full IBIDS Database” to search for “colon cancer” (or a synonym): ·
Angiogenesis inhibitor TNP-470 suppresses growth of peritoneal disseminating foci of human colon cancer line Lovo. Author(s): Department of Surgery, Zhujiang Hospital, The First Military Medical University, Guangzhou 510282, Guangdong Province, China.
[email protected] Source: Fan, Y F Huang, Z H World-J-Gastroenterol. 2002 October; 8(5): 853-6 1007-9327
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Anti-angiogenic therapy and radioimmunotherapy in colon cancer xenografts. Author(s): Department of Nuclear Medicine, Kanazawa University School of Medicine, Ishikawa, Japan.
[email protected] Source: Kinuya, S Kawashima, A Yokoyama, K Kudo, M Kasahara, Y Watanabe, N Shuke, N Bunko, H Michigishi, T Tonami, N Eur-J-Nucl-Med. 2001 September; 28(9): 1306-12 0340-6997
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Anti-tumor efficacy of a novel antisense anti-MDM2 mixed-backbone oligonucleotide in human colon cancer models: p53-dependent and p53-independent mechanisms. Author(s): Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Alabama 352940019, USA. Source: Wang, H Nan, L Yu, D Lindsey, J R Agrawal, S Zhang, R Mol-Med. 2002 April; 8(4): 185-99 1076-1551
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Augmentation of apoptosis and tumor regression by flavopiridol in the presence of CPT-11 in Hct116 colon cancer monolayers and xenografts. Author(s): Gastrointestinal Oncology Research Laboratory, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. Source: Motwani, M Jung, C Sirotnak, F M She, Y Shah, M A Gonen, M Schwartz, G K Clin-Cancer-Res. 2001 December; 7(12): 4209-19 1078-0432
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Augmentation of sodium butyrate-induced apoptosis by phosphatidylinositol 3'kinase inhibition in the KM20 human colon cancer cell line. Author(s): Department of Surgery, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA. Source: Wang, Q Li, N Wang, X Kim, M M Evers, B M Clin-Cancer-Res. 2002 June; 8(6): 1940-7 1078-0432
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Autocrine heregulin generates growth factor independence and blocks apoptosis in colon cancer cells. Author(s): Department of Surgery, University of Texas Health Science Center at San Antonio, Texas, TX 78284, USA. Source: Venkateswarlu, Srinivas Dawson, Dawn M St Clair, Patricia Gupta, Anjana Willson, James K V Brattain, Michael G Oncogene. 2002 Jan 3; 21(1): 78-86 0950-9232
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Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Author(s): Department of Anatomy and Cell Biology, College of Medicine, The University of Florida, Gainesville, Florida, FL 32610, USA. Source: Jaiswal, A S Marlow, B P Gupta, N Narayan, S Oncogene. 2002 December 5; 21(55): 8414-27 0950-9232
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Biosynthesis of the cancer-related sialyl-alpha 2,6-lactosaminyl epitope in colon cancer cell lines expressing beta-galactoside alpha 2,6-sialyltransferase under a constitutive promoter. Author(s): Dipartimento di Patologia Sperimentale, Universita di Bologna, Italy.
[email protected] Source: Dall'Olio, F Chiricolo, M Mariani, E Facchini, A Eur-J-Biochem. 2001 November; 268(22): 5876-84 0014-2956
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Butyrate sensitizes human colon cancer cells to TRAIL-mediated apoptosis. Author(s): Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77555-0536, USA. Source: Hernandez, A Thomas, R Smith, F Sandberg, J Kim, S Chung, D H Evers, B M Surgery. 2001 August; 130(2): 265-72 0039-6060
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Cholecystectomy and the risk for developing colorectal cancer and distal colorectal adenomas. Author(s): Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
[email protected] Source: Schernhammer, E S Leitzmann, M F Michaud, D S Speizer, F E Giovannucci, E Colditz, G A Fuchs, C S Br-J-Cancer. 2003 January 13; 88(1): 79-83 0007-0920
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Classification tree analysis: a statistical tool to investigate risk factor interactions with an example for colon cancer (United States). Author(s): Genetic Epidemiology, Department of Medical Informatics, University of Utah, and Genetic Research, Intermountain Health Care, Salt Lake City 84108, USA.
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Source: Camp, N J Slattery, M L Cancer-Causes-Control. 2002 November; 13(9): 813-23 0957-5243 ·
Colon cancer chemoprevention with ginseng and other botanicals. Author(s): Department of Pathology, University of South Carolina School of Medicine South Carolina Cancer Center Columbia, SC 29203 USA.
[email protected] Source: Wargovich, M J J-Korean-Med-Sci. 2001 December; 16 Suppl: S81-6 1011-8934
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Colon cancer curbed by high-selenium broccoli. Source: McBride, J. Agric-res. Washington, D.C. : Agricultural Research Service, United States Department of Agriculture. June 2000. volume 48 (6) page 12-13. 0002-161X
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Combination of 5-fluorouracil and irinotecan on modulation of thymidylate synthase and topoisomerase I expression and cell cycle regulation in human colon cancer LoVo cells: clinical relevance. Author(s): Beijing 307 Hospital Cancer Center, China. Source: Xu, J M Azzariti, A Tommasi, S Lacalamita, R Colucci, G Johnston, P G Church, S W Paradiso, A Clin-Colorectal-Cancer. 2002 November; 2(3): 182-8 1533-0028
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Dietary sphingolipids in colorectal cancer prevention. Author(s): Institute of General Physiology and Biological Chemistry, School of Pharmacy, University of Milan, Italy. Source: Berra, B Colombo, I Sottocornola, E Giacosa, A Eur-J-Cancer-Prevolume 2002 April; 11(2): 193-7 0959-8278
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Docosahexaenoic acid regulated genes and transcription factors inducing apoptosis in human colon cancer cells. Author(s): Microarray Systems Laboratory, Molecular Pathology and Bioinformatics Facility, American Health Foundation, Valhalla, NY, USA. Source: Narayanan, B A Narayanan, N K Reddy, B S Int-J-Oncol. 2001 December; 19(6): 1255-62 1019-6439
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Effect of Cocos nucifera and red chilli on intestinal beta-glucuronidase and mucinase activity in experimental colon cancer. Author(s): Department of Biochemistry, Annamalai University, Annamalainagar 608 002, Tamil Nadu (India) Source: Nalini, N. Chitra, S. Sabitha, K. Viswanathan, P. Menon, V.P. Asia-PacificJournal-of-Clinical-Nutrition (United Kingdom). (1996). volume 5(2) page 96-99.
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Effect of selenium deficiency on 1,2-dimethylhydrazine-induced colon cancer in rats. Source: Pence, B.C. Buddingh, F. Selenium in biology and medicine : proceedings of the Third International Symposium on Selenium in Biology and Medicine, held May 27-June 1, 1984, Xiangshan (Fragrance Hills) Hotel Beijing, People's Republic of China. New York : Van Nostrand Reinhold, c1987. page 1053-1059. ISBN: 0442221088
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Effects of alcohol consumption on the risk of colorectal cancer among men by anatomical subsite (Canada). Author(s): Epidemiology and Biostatistics Unit, INRS-Institut Armand-Frappier, Universite du Quebec, Laval, Canada. Source: Sharpe, C R Siemiatycki, J Rachet, B Cancer-Causes-Control. 2002 June; 13(5): 483-91 0957-5243
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Estrogen and colon cancer: current issues. Author(s): Gynaecology Research Unit, Department of Obstetrics and Gynaecology, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, LE2 7LX, UK.
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Source: al Azzawi, F Wahab, M Climacteric. 2002 March; 5(1): 3-14 1369-7137 ·
Expression of paclitaxel-inactivating CYP3A activity in human colorectal cancer: implications for drug therapy. Author(s): Department of Pharmacology, Medical School, University of Extremadura, Avda. de Elvas s/n, E-06071, Badajoz, Spain. Source: Martinez, C Garcia Martin, E Pizarro, R M Garcia Gamito, F J Agundez, J A Br-JCancer. 2002 September 9; 87(6): 681-6 0007-0920
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Folate may reduce colon cancer risk. Source: Tufts-Univ-health-nutr-lett. New York, NY : Tufts University Health & Nutrition Letter, c1997-. December 1998. volume 16 (10) page 1, 6.
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Folic acid lowers colon cancer risk. Source: Anonymous Health-News. 2002 May; 8(5): 5 1081-5880
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Health behavior changes after colon cancer: a comparison of findings from face-toface and on-line focus groups. Author(s): Department of Nutrition, Program Leader, Lineberger Comprehensive Cancer Center, University of North Carolona, Chapel Hill, USA. Source: Kramish Campbell, M Meier, A Carr, C Enga, Z James, A S Reedy, J Zheng, B Fam-Community-Health. 2001 October; 24(3): 88-103 0160-6379
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Identification of Src transformation fingerprint in human colon cancer. Author(s): Department of Functional Genomics, The Institute for Genomic Research, 9712 Medical Center Dr, Rockville, Maryland, MD 20850, USA. Source: Malek, R L Irby, R B Guo, Q M Lee, K Wong, S He, M Tsai, J Frank, B Liu, E T Quackenbush, J Jove, R Yeatman, T J Lee, N H Oncogene. 2002 October 17; 21(47): 725665 0950-9232
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Improved response of colon cancer xenografts to radioimmunotherapy with pentoxifylline treatment. Author(s): Department of Nuclear Medicine, Kanazawa University School of Medicine, Ishikawa, Japan.
[email protected] Source: Kinuya, S Yokoyama, K Konishi, S Li, X F Watanabe, N Shuke, N Takayama, T Bunko, H Michigishi, T Tonami, N Eur-J-Nucl-Med. 2001 June; 28(6): 750-5 0340-6997
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Inhibitory effects of evodiamine on in vitro invasion and experimental lung metastasis of murine colon cancer cells. Author(s): Toyama Prefectural Institute for Pharmaceutical Research, Japan. masaru@
[email protected] Source: Ogasawara, M Matsubara, T Suzuki, H Biol-Pharm-Bull. 2001 August; 24(8): 91720 0918-6158
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Involvement of both extracellular signal-regulated kinase and c-jun N-terminal kinase pathways in the 12-O-tetradecanoylphorbol-13-acetate-induced upregulation of p21(Cip1) in colon cancer cells. Author(s): Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan. Source: Lin, S Y Liang, Y C Ho, Y S Tsai, S H Pan, S Lee, W S Mol-Carcinog. 2002 September; 35(1): 21-8 0899-1987
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Modulation of the Fas signaling pathway by IFN-gamma in therapy of colon cancer: phase I trial and correlative studies of IFN-gamma, 5-fluorouracil, and leucovorin. Author(s): The West Clinic, Memphis, Tennessee 38120, USA.
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Source: Schwartzberg, L S Petak, I Stewart, C Turner, P K Ashley, J Tillman, D M Douglas, L Tan, M Billups, C Mihalik, R Weir, A Tauer, K Shope, S Houghton, J A ClinCancer-Res. 2002 August; 8(8): 2488-98 1078-0432 ·
Monoclonal antibodies recognizing epitopes of calretinins: dependence on Ca2+binding status and differences in antigen accessibility in colon cancer cells. Author(s): Institute of Histology and General Embryology, University of Fribourg, Switzerland. Source: Zimmermann, L Schwaller, B Cell-Calcium. 2002 January; 31(1): 13-25 0143-4160
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Multivitamin use and colon cancer mortality in the Cancer Prevention Study II cohort (United States). Author(s): Department of Epidemiology and Surveillance Research, American Cancer Society, National Home Office, Atlanta, GA 30329-4251, USA. Source: Jacobs, E J Connell, C J Patel, A V Chao, A Rodriguez, C Seymour, J McCullough, M L Calle, E E Thun, M J Cancer-Causes-Control. 2001 December; 12(10): 927-34 0957-5243
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Nutrition and colon cancer prevention. Author(s): South Carolina Cancer Center, University of South Carolina, Columbia, S.C., USA. Source: Bostick, R M Nestle-Nutr-Workshop-Ser-Clin-Perform-Programme. 2000; 4: 6785; discussion 85-6 1422-7584
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Nutritional chemoprevention of colon cancer. Author(s): Department of Internal Medicine, Tufts University School of Medicine, Boston, MA, USA.
[email protected] Source: Mason, J B Semin-Gastrointest-Dis. 2002 July; 13(3): 143-53 1049-5118
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Pemetrexed disodium combined with oxaliplatin, SN38, or 5-fluorouracil, based on the quantitation of drug interactions in human HT29 colon cancer cells. Author(s): INSERM U482, Hopital Saint Antoine, Paris, France.
[email protected] Source: Raymond, E Louvet, C Tournigand, C Coudray, A M Faivre, S De Gramont, A Gespach, C Int-J-Oncol. 2002 August; 21(2): 361-7 1019-6439
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Perturbation by geraniol of cell membrane permeability and signal transduction pathways in human colon cancer cells. Author(s): Laboratory of Nutritional Oncology, Institut National de la Sante et de la Recherche Medicale, Strasbourg, France. Source: Carnesecchi, S Bradaia, A Fischer, B Coelho, D Scholler Guinard, M Gosse, F Raul, F J-Pharmacol-Exp-Ther. 2002 November; 303(2): 711-5 0022-3565
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Physical exercise, use of Plantago ovata and aspirin, and reduced risk of colon cancer. Author(s): Community Health Center of Area 4, Madrid, Spain. Source: Juarranz, M Calle Puron, M E Gonzalez Navarro, A Regidor Poyatos, E Soriano, T Martinez Hernandez, D Rojas, V D Guinee, V F Eur-J-Cancer-Prevolume 2002 October; 11(5): 465-72 0959-8278
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Prevention of colon cancer: role of short chain fatty acids produced by intestinal flora. Author(s): Department of Medicine, Queen Elizabeth Hospital, University of Adelaide, Adelaide, South Australia 5011 (Australia) Source: Young, G.P. Asia-Pacific-Journal-of-Clinical-Nutrition (United Kingdom). (1996). volume 5(1) page 44-47.
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Probiotics and colon cancer prevention. Author(s): CSIRO Division of Human Nutrition, GPO Box 10041, Gouger Street, Adelaide, South Australia 5000 (Australia)
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Source: McIntosh, G.H. Asia-Pacific-Journal-of-Clinical-Nutrition (United Kingdom). (1996). volume 5(1) page 48-52. ·
Prognostic value of thymidylate synthase, Ki-67, and p53 in patients with Dukes' B and C colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project collaborative study. Author(s): Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-2440, USA.
[email protected] Source: Allegra, C J Paik, S Colangelo, L H Parr, A L Kirsch, I Kim, G Klein, P Johnston, P G Wolmark, N Wieand, H S J-Clin-Oncol. 2003 January 15; 21(2): 241-50 0732-183X
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Protective effect of acetaminophen against colon cancer initiation effects of 3,2'dimethyl-4-aminobiphenyl in rats. Author(s): Department of Pathology, New York Medical University, Valhalla, NY 10595, USA.
[email protected] Source: Williams, G M Iatropoulos, M J Jeffrey, A M Shirai, T Eur-J-Cancer-Prevolume 2002 February; 11(1): 39-48 0959-8278
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Resistance to apoptosis is increased during metastatic dissemination of colon cancer. Author(s): INSERM U 419, IFR 26, Nantes, France.
[email protected] Source: Oliver, L Cordel, S Barbieux, I LeCabellec, M T Meflah, K Gregoire, M Vallette, F M Clin-Exp-Metastasis. 2002; 19(2): 175-80 0262-0898
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Saponins-mediated potentiation of cisplatin accumulation and cytotoxicity in human colon cancer cells. Source: Gaidi, G. Correia, M. Chauffert, B. Beltramo, J.L. Wagner, H. Lacaille Dubois, M.A. Planta-med. Stuttgart : Georg Thieme Verlag,. January 2002. volume 68 (1) page 7072. 0032-0943
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Sphingoid bases and ceramide induce apoptosis in HT-29 and HCT-116 human colon cancer cells. Author(s): Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824-1224, USA. Source: Ahn, Eun Hyun Schroeder, Joseph J Exp-Biol-Med-(Maywood). 2002 May; 227(5): 345-53 1535-3702
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Stromal extracellular matrix reduces chemotherapy-induced apoptosis in colon cancer cell lines. Author(s): Surgical Oncology Department, Sheba Medical Center, Tel Hashomer, Israel. Source: Kouniavsky, Guenadi Khaikin, Marat Zvibel, Isabel Zippel, Dov Brill, Shlomo Halpern, Zamir Papa, Moshe Clin-Exp-Metastasis. 2002; 19(1): 55-60 0262-0898
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Studies on the development of colon-targeted delivery systems for celecoxib in the prevention of colorectal cancer. Author(s): Department of Pharmaceutical Sciences, Andhra University, India.
[email protected] Source: Krishnaiah, Y S Satyanarayana, V KuMarch, B D Karthikeyan, R S J-DrugTarget. 2002 May; 10(3): 247-54 1061-186X
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Suppression of serum-induced c-jun expression by activated Ki-ras in human colon cancer cells. Author(s): Department of Genetics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-82, Japan. Source: Furuse, M Shirasawa, S Okumura, K Ohmori, M Sasazuki, T Jpn-J-Hum-Genet. 1997 September; 42(3): 409-16 0916-8478
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Systemic irinotecan or regional floxuridine chemotherapy prolongs survival after hepatic cryosurgery in patients with metastatic colon cancer refractory to 5fluorouracil. Author(s): John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA, USA.
[email protected] Source: Bilchik, A J Wood, T F Chawla, S P Rose, D M Chung, M H Stern, S S Foshag, L J Ramming, K P Clin-Colorectal-Cancer. 2001 May; 1(1): 36-42 1533-0028
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Ten-year study further links colon cancer, red meat. Source: Willett, W.C. Stampfer, M.J. Colditz, G.A. Rosner, B.A. Speizer, F.E. Nutr-Week. Washington, D.C. : Community Nutrition Institute. December 21, 1990. volume 20 (50) page 6-7. 0736-0096
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The cytotoxic effect of mistletoe lectins I, II and III on sensitive and multidrug resistant human colon cancer cell lines in vitro. Author(s): Institute for Anatomy, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
[email protected] Source: Valentiner, Ursula Pfuller, Uwe Baum, Christopher Schumacher, Udo Toxicology. 2002 February 28; 171(2-3): 187-99 0300-483X
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The effect of angiogenesis inhibitor TNP-470 against postoperative lung metastasis following removal of orthotopic transplanted human colon cancer: an experimental study. Author(s): Department of Surgery, Kurume University School of Medicine, 67 Asahimachi, Kurume 830-0011, Japan. Source: Oda, H Ogata, Y Shirouzu, K Kurume-Med-J. 2001; 48(4): 285-93 0023-5679
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The effect of dietary fat and yoghurt on colonic bacterial enzymes (beta-glucosidase and beta-glucuronidase) associated with colon cancer. Source: Cole, C.B. Fuller, R. Food-Microbiol. London : Academic Press. January 1987. volume 4 (1) page 77-81. 0740-0020
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The role of plant components, specially fibers, in preventive nutrition [colon cancer, plasma lipids]. Author(s): Institut National de la Recherche Agronomique, Saint Genes Champanelle (France). Centre de Clermont Ferrand Theix, Maladies Metaboliques Source: Remesy, C. Demigne, C. Levrat, M.A. Medecine-et-Nutrition (France). (1994). volume 30(4) page 189-198. 0398-7604
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To fight colon cancer, high-fiber diet still a good bet. Source: Tufts-Univ-health-nutr-lett. New York, NY : Tufts University Health & Nutrition Letter, c1997-. March 1999. volume 17 (1) page 7.
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Upregulation of vascular endothelial growth factor by hydrogen peroxide in human colon cancer. Author(s): Shanghai Institute of Digestive Sugery,Ruijin Hospital,Shanghai Second Medical University,Shanghai 200025,China.
[email protected] Source: Zhu, Jian Wei Yu, Bao Ming Ji, Yu Bao Zheng, Ming Hua Li, Dong Hua World-JGastroenterol. 2002 February; 8(1): 153-7 1007-9327
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Vaticanol C, a novel resveratrol tetramer, inhibits cell growth through induction of apoptosis in colon cancer cell lines. Author(s): Gifu Pharmaceutical University, Mitahora-higashi, Japan. Source: Ito, Tetsuro Akao, Yukihiro Tanaka, Toshiyuki Iinuma, Munekazu Nozawa, Yoshinori Biol-Pharm-Bull. 2002 January; 25(1): 147-8 0918-6158
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Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: ·
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: ·
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDÒHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html
The following is a specific Web list relating to colon cancer; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation (some Web sites are subscription based):
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Vitamins Folic Acid Source: Healthnotes, Inc. www.healthnotes.com Vitamin C Source: Healthnotes, Inc. www.healthnotes.com Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin C Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,904,00.html Vitamin D Source: Healthnotes, Inc. www.healthnotes.com Vitamin D Alternative names: Calciferol, Calcitrol, Cholecalciferol, Erocalciferol Source: Integrative Medicine Communications; www.drkoop.com Vitamin D Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin D Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,905,00.html Vitamin E Source: Healthnotes, Inc. www.healthnotes.com Vitamin E Alternative names: Alpha-Tocopherol, Beta-Tocopherol, D-Alpha-Tocopherol, Delta-Tocopherol, Gamma-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Vitamin E Source: Prima Communications, Inc.www.personalhealthzone.com
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Minerals Alpha-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Beta-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com
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Calcium Source: Healthnotes, Inc. www.healthnotes.com Calcium Source: Prima Communications, Inc.www.personalhealthzone.com Calcium Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,884,00.html Cisplatin Source: Healthnotes, Inc. www.healthnotes.com D-Alpha-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Delta-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Folate Source: Prima Communications, Inc.www.personalhealthzone.com Gamma-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Iron Source: Healthnotes, Inc. www.healthnotes.com Selenium Source: Healthnotes, Inc. www.healthnotes.com Selenium Source: Prima Communications, Inc.www.personalhealthzone.com ·
Food and Diet Garlic Alternative names: Allium sativum Source: Healthnotes, Inc. www.healthnotes.com Garlic Source: Prima Communications, Inc.www.personalhealthzone.com Garlic Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,21,00.html
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Hazelnuts Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,307,00.html High-Fiber Diet Source: Healthnotes, Inc. www.healthnotes.com Low-Salt Diet Source: Healthnotes, Inc. www.healthnotes.com Omega-3 Fatty Acids Source: Integrative Medicine Communications; www.drkoop.com Omega-3 fatty acids Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,992,00.html Soy Source: Healthnotes, Inc. www.healthnotes.com Soy Source: Prima Communications, Inc.www.personalhealthzone.com Vegetarian Diet Source: Healthnotes, Inc. www.healthnotes.com Wheat Source: Healthnotes, Inc. www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND COLON CANCER Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to colon cancer. At the conclusion of this chapter, we will provide additional sources.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to colon cancer and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “colon cancer” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to colon cancer: ·
29. F-18 FDG PET for Suspected or Confirmed Regional Recurrence of Colon Cancer. A Prospective Study of Impact and Outcome. Author(s): Kalff V V, Hicks R, Ware R, Binns D, McKenzie A. Source: Clinical Positron Imaging : Official Journal of the Institute for Clinical P.E.T. 2000 July; 3(4): 183. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11150786&dopt=Abstract
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A diet containing alpha-cellulose and fish oil reduces aberrant crypt foci formation and modulates other possible markers for colon cancer risk in azoxymethane-treated rats. Author(s): Coleman LJ, Landstrom EK, Royle PJ, Bird AR, McIntosh GH. Source: The Journal of Nutrition. 2002 August; 132(8): 2312-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163681&dopt=Abstract
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A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. Author(s): Sargent DJ, Goldberg RM, Jacobson SD, Macdonald JS, Labianca R, Haller DG, Shepherd LE, Seitz JF, Francini G. Source: The New England Journal of Medicine. 2001 October 11; 345(15): 1091-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11596588&dopt=Abstract
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A prospective study of 2-[18F] fluoro-2-deoxy-D-glucose/positron emission tomography scan, 99mTc-labeled arcitumomab (CEA-scan), and blind second-look laparotomy for detecting colon cancer recurrence in patients with increasing carcinoembryonic antigen levels. Author(s): Libutti SK, Alexander HR Jr, Choyke P, Bartlett DL, Bacharach SL, Whatley M, Jousse F, Eckelman WC, Kranda K, Neumann RD, Carrasquillo JA. Source: Annals of Surgical Oncology : the Official Journal of the Society of Surgical Oncology. 2001 December; 8(10): 779-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11776491&dopt=Abstract
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A prospective study on supplemental vitamin e intake and risk of colon cancer in women and men. Author(s): Wu K, Willett WC, Chan JM, Fuchs CS, Colditz GA, Rimm EB, Giovannucci EL. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 November; 11(11): 1298-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433706&dopt=Abstract
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A water-soluble extract from cultured medium of Ganoderma lucidum (Rei-shi) mycelia suppresses azoxymethane-induction of colon cancers in male F344 rats. Author(s): Lu H, Kyo E, Uesaka T, Katoh O, Watanabe H. Source: Oncol Rep. 2003 March-April; 10(2): 375-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12579275&dopt=Abstract
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Adjuvant chemotherapy for colon cancer. Author(s): Ducreux M, Boige V. Source: Best Practice & Research. Clinical Gastroenterology. 2002 April; 16(2): 283-98. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11969239&dopt=Abstract
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Adjuvant chemotherapy for colon cancer. Author(s): Kumar SK, Goldberg RM. Source: Current Oncology Reports. 2001 March; 3(2): 94-101. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11177740&dopt=Abstract
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Adjuvant chemotherapy for colon cancer: the US experience. Author(s): Haller DG. Source: Tumori. 2001 January-February; 87(1 Suppl 1): S86-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11300040&dopt=Abstract
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Adjuvant chemotherapy in colon cancer: what is the evidence? Author(s): Haydon A. Source: Internal Medicine Journal. 2003 March; 33(3): 119-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603585&dopt=Abstract
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Adjuvant effect of a Flt3 ligand (FL) gene-transduced xenogeneic cell line in a murine colon cancer model. Author(s): Kim EM, Sivanandham M, Stavropoulos CI, Wallack MK. Source: The Journal of Surgical Research. 2002 November; 108(1): 148-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12443727&dopt=Abstract
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Adjuvant therapy for colon cancer in the new millenium. Author(s): Rao S, Cunningham D. Source: Scand J Surg. 2003; 92(1): 57-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705552&dopt=Abstract
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Adjuvant therapy for colon cancer: the European experience. Author(s): Wils J. Source: Tumori. 2001 January-February; 87(1 Suppl 1): S85. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11300039&dopt=Abstract
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Adjuvant therapy of colon cancer. Author(s): Macdonald JS. Source: Ca: a Cancer Journal for Clinicians. 1999 July-August; 49(4): 202-19. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11198882&dopt=Abstract
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Adjuvant therapy of colon cancer. Author(s): Macdonald JS, Astrow AB. Source: Seminars in Oncology. 2001 February; 28(1): 30-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11254865&dopt=Abstract
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Adjuvant therapy of colon cancer: a review. Author(s): Hobday TJ, Erlichman C. Source: Clin Colorectal Cancer. 2002 February; 1(4): 230-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450421&dopt=Abstract
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Anti-angiogenic effect of silymarin on colon cancer LoVo cell line. Author(s): Yang SH, Lin JK, Chen WS, Chiu JH. Source: The Journal of Surgical Research. 2003 July; 113(1): 133-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943822&dopt=Abstract
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Antiproliferative effects of S-allylmercaptocysteine on colon cancer cells when tested alone or in combination with sulindac sulfide. Author(s): Shirin H, Pinto JT, Kawabata Y, Soh JW, Delohery T, Moss SF, Murty V, Rivlin RS, Holt PR, Weinstein IB. Source: Cancer Research. 2001 January 15; 61(2): 725-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11212275&dopt=Abstract
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Anti-tumor efficacy of a novel antisense anti-MDM2 mixed-backbone oligonucleotide in human colon cancer models: p53-dependent and p53-independent mechanisms. Author(s): Wang H, Nan L, Yu D, Lindsey JR, Agrawal S, Zhang R. Source: Molecular Medicine (Cambridge, Mass.). 2002 April; 8(4): 185-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149568&dopt=Abstract
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Apoptosis cascade proteins are regulated in vivo by high intracolonic butyrate concentration: correlation with colon cancer inhibition. Author(s): Avivi-Green C, Polak-Charcon S, Madar Z, Schwartz B. Source: Oncology Research. 2000; 12(2): 83-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11132927&dopt=Abstract
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Apoptosis induction by wheat-flour sphingoid bases in DLD-1 human colon cancer cells. Author(s): Sugawara T, Kinoshita M, Ohnishi M, Miyazawa T. Source: Biosci Biotechnol Biochem. 2002 October; 66(10): 2228-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450138&dopt=Abstract
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Augmentation of apoptosis and tumor regression by flavopiridol in the presence of CPT-11 in Hct116 colon cancer monolayers and xenografts. Author(s): Motwani M, Jung C, Sirotnak FM, She Y, Shah MA, Gonen M, Schwartz GK. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2001 December; 7(12): 4209-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751522&dopt=Abstract
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Awareness and barriers to use of cancer support and information resources by HMO patients with breast, prostate, or colon cancer: patient and provider perspectives. Author(s): Eakin EG, Strycker LA.
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Source: Psycho-Oncology. 2001 March-April; 10(2): 103-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11268137&dopt=Abstract ·
Bax induction activates apoptotic cascade via mitochondrial cytochrome c release and Bax overexpression enhances apoptosis induced by chemotherapeutic agents in DLD1 colon cancer cells. Author(s): Kobayashi T, Sawa H, Morikawa J, Zhang W, Shiku H. Source: Japanese Journal of Cancer Research : Gann. 2000 December; 91(12): 1264-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11123425&dopt=Abstract
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Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells. Author(s): Liu JJ, Nilsson A, Oredsson S, Badmaev V, Zhao WZ, Duan RD. Source: Carcinogenesis. 2002 December; 23(12): 2087-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507932&dopt=Abstract
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Chemoprevention of colon cancer by Korean food plant components. Author(s): Kim DJ, Shin DH, Ahn B, Kang JS, Nam KT, Park CB, Kim CK, Hong JT, Kim YB, Yun YW, Jang DD, Yang KH. Source: Mutation Research. 2003 February-March; 523-524: 99-107. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628507&dopt=Abstract
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Colon cancer chemoprevention with ginseng and other botanicals. Author(s): Wargovich MJ. Source: Journal of Korean Medical Science. 2001 December; 16 Suppl: S81-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11748382&dopt=Abstract
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Colon cancer: detection and prevention. Author(s): Loren DE, Lewis J, Kochman ML. Source: Gastroenterology Clinics of North America. 2002 June; 31(2): 565-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12134619&dopt=Abstract
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Combination of 5-fluorouracil and irinotecan on modulation of thymidylate synthase and topoisomerase I expression and cell cycle regulation in human colon cancer LoVo cells: clinical relevance. Author(s): Xu JM, Azzariti A, Tommasi S, Lacalamita R, Colucci G, Johnston PG, Church SW, Paradiso A. Source: Clin Colorectal Cancer. 2002 November; 2(3): 182-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482336&dopt=Abstract
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Combination of oxaliplatin and irinotecan on human colon cancer cell lines: activity in vitro and in vivo. Author(s): Guichard S, Arnould S, Hennebelle I, Bugat R, Canal P.
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Source: Anti-Cancer Drugs. 2001 October; 12(9): 741-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11593056&dopt=Abstract ·
Combination therapy with paclitaxel and thalidomide inhibits angiogenesis and growth of human colon cancer xenograft in mice. Author(s): Fujii T, Tachibana M, Dhar DK, Ueda S, Kinugasa S, Yoshimura H, Kohno H, Nagasue N. Source: Anticancer Res. 2003 May-June; 23(3B): 2405-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894521&dopt=Abstract
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Dietary soy reduces colon carcinogenesis in human and rats. Soy and colon cancer. Author(s): Bennink MR. Source: Advances in Experimental Medicine and Biology. 2001; 492: 11-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480660&dopt=Abstract
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Docosahexaenoic acid is a potent inducer of apoptosis in HT-29 colon cancer cells. Author(s): Chen ZY, Istfan NW. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2000 November; 63(5): 301-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11090257&dopt=Abstract
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Docosahexaenoic acid regulated genes and transcription factors inducing apoptosis in human colon cancer cells. Author(s): Narayanan BA, Narayanan NK, Reddy BS. Source: International Journal of Oncology. 2001 December; 19(6): 1255-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11713597&dopt=Abstract
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Drg1, a novel target for modulating sensitivity to CPT-11 in colon cancer cells. Author(s): Motwani M, Sirotnak FM, She Y, Commes T, Schwartz GK. Source: Cancer Research. 2002 July 15; 62(14): 3950-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124325&dopt=Abstract
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Edrecolomab alone or in combination with fluorouracil and folinic acid in the adjuvant treatment of stage III colon cancer: a randomised study. Author(s): Punt CJ, Nagy A, Douillard JY, Figer A, Skovsgaard T, Monson J, Barone C, Fountzilas G, Riess H, Moylan E, Jones D, Dethling J, Colman J, Coward L, MacGregor S. Source: Lancet. 2002 August 31; 360(9334): 671-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12241873&dopt=Abstract
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Effect of folate supplementation on mucosal cell proliferation in high risk patients for colon cancer. Author(s): Khosraviani K, Weir HP, Hamilton P, Moorehead J, Williamson K.
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Source: Gut. 2002 August; 51(2): 195-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117879&dopt=Abstract ·
Effects of folate supplementation on two provisional molecular markers of colon cancer: a prospective, randomized trial. Author(s): Kim YI, Baik HW, Fawaz K, Knox T, Lee YM, Norton R, Libby E, Mason JB. Source: The American Journal of Gastroenterology. 2001 January; 96(1): 184-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11197251&dopt=Abstract
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Effects of lyophilized black raspberries on azoxymethane-induced colon cancer and 8hydroxy-2'-deoxyguanosine levels in the Fischer 344 rat. Author(s): Harris GK, Gupta A, Nines RG, Kresty LA, Habib SG, Frankel WL, LaPerle K, Gallaher DD, Schwartz SJ, Stoner GD. Source: Nutrition and Cancer. 2001; 40(2): 125-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11962247&dopt=Abstract
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Efficacy of adjuvant fluorouracil and leucovorin in stage B2 and C colon cancer. International Multicenter Pooled Analysis of Colon Cancer Trials Investigators. Author(s): Marsoni S; International Multicenter Pooled Analysis of Colon Cancer Trials Investigators. Source: Seminars in Oncology. 2001 February; 28(1 Suppl 1): 14-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11273584&dopt=Abstract
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Efficacy of combination chemotherapy for stage IV colon cancer with extensive peritoneal dissemination and multiple liver metastases: a case report. Author(s): Mukai M, Oida Y, Mukoyama S, Okamoto Y, Ito I, Nakasaki H, Kawai K, Sato S, Makuuchi H. Source: Oncol Rep. 2002 November-December; 9(6): 1339-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375045&dopt=Abstract
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Efficient induction of apoptosis by ONYX-015 adenovirus in human colon cancer cell lines regardless of p53 status. Author(s): Petit T, Davidson KK, Cerna C, Lawrence RA, Von Hoff DD, Heise C, Kirn D, Izbicka E. Source: Anti-Cancer Drugs. 2002 January; 13(1): 47-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11914640&dopt=Abstract
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Enhanced clearance of topoisomerase I inhibitors from human colon cancer cells by glucuronidation. Author(s): Cummings J, Boyd G, Ethell BT, Macpherson JS, Burchell B, Smyth JF, Jodrell DI.
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Source: Biochemical Pharmacology. 2002 February 15; 63(4): 607-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992628&dopt=Abstract ·
Estrogen receptor beta mRNA in colon cancer cells: growth effects of estrogen and genistein. Author(s): Arai N, Strom A, Rafter JJ, Gustafsson JA. Source: Biochemical and Biophysical Research Communications. 2000 April 13; 270(2): 425-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10753641&dopt=Abstract
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Fluorouracil plus leucovorin as effective adjuvant chemotherapy in curatively resected stage III colon cancer: results of the trial adjCCA-01. Author(s): Porschen R, Bermann A, Loffler T, Haack G, Rettig K, Anger Y, Strohmeyer G; Arbeitsgemeinschaft Gastrointestinale Onkologie. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 March 15; 19(6): 1787-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11251010&dopt=Abstract
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Health behavior changes after colon cancer: a comparison of findings from face-toface and on-line focus groups. Author(s): Kramish Campbell M, Meier A, Carr C, Enga Z, James AS, Reedy J, Zheng B. Source: Family & Community Health. 2001 October; 24(3): 88-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11563947&dopt=Abstract
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In vitro and in vivo tracer characteristics of an established multidrug-resistant human colon cancer cell line. Author(s): Lorke DE, Kruger M, Buchert R, Bohuslavizki KH, Clausen M, Schumacher U. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2001 April; 42(4): 646-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11337555&dopt=Abstract
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Inhibition of cyclin A kinase activity in E2F-1 chemogene therapy of colon cancer. Author(s): Elliott MJ, Baker JD, Dong YB, Yang HL, Gleason Jr JF, McMasters KM. Source: Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine. 2002 November-December; 23(6): 324-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12677090&dopt=Abstract
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Inhibitory effects of evodiamine on in vitro invasion and experimental lung metastasis of murine colon cancer cells. Author(s): Ogasawara M, Matsubara T, Suzuki H.
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Source: Biological & Pharmaceutical Bulletin. 2001 August; 24(8): 917-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11510485&dopt=Abstract ·
Irinotecan-based combinations for the adjuvant treatment of stage III colon cancer. Author(s): Saltz L. Source: Oncology (Huntingt). 2000 December; 14(12 Suppl 14): 47-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11200149&dopt=Abstract
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Long-term survival following treatment with antineoplastons for colon cancer with unresectable multiple liver metastases: report of a case. Author(s): Ogata Y, Tsuda H, Matono K, Kumabe T, Saitsu H, Hara H, Akagi Y, Araki Y, Sata M, Shirouzu K. Source: Surgery Today. 2003; 33(6): 448-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768372&dopt=Abstract
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Modification of the sensitivity to cisplatin with c-myc over-expression or downregulation in colon cancer cells. Author(s): Funato T, Kozawa K, Kaku M, Sasaki T. Source: Anti-Cancer Drugs. 2001 November; 12(10): 829-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11707650&dopt=Abstract
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Modulation of inducible nitric oxide synthase and related proinflammatory genes by the omega-3 fatty acid docosahexaenoic acid in human colon cancer cells. Author(s): Narayanan BA, Narayanan NK, Simi B, Reddy BS. Source: Cancer Research. 2003 March 1; 63(5): 972-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615711&dopt=Abstract
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Monthly 5-days 5-fluorouracil and low-dose leucovorin for adjuvant chemotherapy in colon cancer. Author(s): Ahn JB, Shim KY, Jeung HC, Rha SY, Yoo NC, Kim NK, Roh JK, Min JS, Kim BS, Chung HC. Source: Cancer Letters. 2001 June 26; 167(2): 215-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11369143&dopt=Abstract
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Most effective colon cancer chemopreventive agents in rats: a systematic review of aberrant crypt foci and tumor data, ranked by potency. Author(s): Corpet DE, Tache S. Source: Nutrition and Cancer. 2002; 43(1): 1-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467130&dopt=Abstract
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Multivitamins, folate, and colon cancer. Author(s): Little J.
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Source: Gut. 2001 January; 48(1): 12-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11115816&dopt=Abstract ·
National Surgical Adjuvant Breast and Bowel Project trials in colon cancer. Author(s): Wolmark N, Colangelo L, Wieand S. Source: Seminars in Oncology. 2001 February; 28(1 Suppl 1): 9-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11273592&dopt=Abstract
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Nitric oxide suppresses apoptosis in human colon cancer cells by scavenging mitochondrial superoxide anions. Author(s): Wenzel U, Kuntz S, De Sousa UJ, Daniel H. Source: International Journal of Cancer. Journal International Du Cancer. 2003 September 20; 106(5): 666-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866025&dopt=Abstract
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North Central Cancer Treatment Group--Mayo Clinic trials in colon cancer. Author(s): O'Connell MJ. Source: Seminars in Oncology. 2001 February; 28(1 Suppl 1): 4-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11273589&dopt=Abstract
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Novel approaches for colon cancer prevention by cyclooxygenase-2 inhibitors. Author(s): Reddy BS, Rao CV. Source: Journal of Environmental Pathology, Toxicology and Oncology : Official Organ of the International Society for Environmental Toxicology and Cancer. 2002; 21(2): 15564. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086402&dopt=Abstract
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Older patients with colon cancer: is adjuvant chemotherapy safe and effective? Author(s): Arora A, Potter J. Source: Journal of the American Geriatrics Society. 2003 April; 51(4): 567-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657083&dopt=Abstract
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PC-SPES inhibits colon cancer growth in vitro and in vivo. Author(s): Huerta S, Arteaga JR, Irwin RW, Ikezoe T, Heber D, Koeffler HP. Source: Cancer Research. 2002 September 15; 62(18): 5204-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234985&dopt=Abstract
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Pemetrexed disodium combined with oxaliplatin, SN38, or 5-fluorouracil, based on the quantitation of drug interactions in human HT29 colon cancer cells. Author(s): Raymond E, Louvet C, Tournigand C, Coudray AM, Faivre S, De Gramont A, Gespach C.
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Source: International Journal of Oncology. 2002 August; 21(2): 361-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12118332&dopt=Abstract ·
Phase I and pharmacokinetic study of intravenous irinotecan plus oral ciclosporin in patients with fuorouracil-refractory metastatic colon cancer. Author(s): Chester JD, Joel SP, Cheeseman SL, Hall GD, Braun MS, Perry J, Davis T, Button CJ, Seymour MT. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 March 15; 21(6): 1125-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637480&dopt=Abstract
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Physical exercise, use of Plantago ovata and aspirin, and reduced risk of colon cancer. Author(s): Juarranz M, Calle-Puron ME, Gonzalez-Navarro A, Regidor-Poyatos E, Soriano T, Martinez-Hernandez D, Rojas VD, Guinee VF. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 2002 October; 11(5): 465-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394244&dopt=Abstract
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Phytoestrogens and 17beta-estradiol influence vitamin D metabolism and receptor expression-relevance for colon cancer prevention. Author(s): Lechner D, Cross HS. Source: Recent Results Cancer Res. 2003; 164: 379-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899537&dopt=Abstract
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Prognostic value of thymidylate synthase, Ki-67, and p53 in patients with Dukes' B and C colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project collaborative study. Author(s): Allegra CJ, Paik S, Colangelo LH, Parr AL, Kirsch I, Kim G, Klein P, Johnston PG, Wolmark N, Wieand HS. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 January 15; 21(2): 241-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525515&dopt=Abstract
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Protective role of probiotics and prebiotics in colon cancer. Author(s): Wollowski I, Rechkemmer G, Pool-Zobel BL. Source: The American Journal of Clinical Nutrition. 2001 February; 73(2 Suppl): 451S455S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11157356&dopt=Abstract
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Repetitive mucosal trauma promotes colon cancer in experimental rat model. Author(s): Vinas Salas J, Pinol Felis C, Ferminan A, Egido R, Perez-Holanda S, Biendicho P, Buenestado J, Rene Espinet J.
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Source: Rev Esp Enferm Dig. 2001 March; 93(3): 140-7. English, Spanish. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11469074&dopt=Abstract ·
Resveratrol enhances the differentiation induced by butyrate in caco-2 colon cancer cells. Author(s): Wolter F, Stein J. Source: The Journal of Nutrition. 2002 July; 132(7): 2082-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12097697&dopt=Abstract
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Role of p21 in apoptosis and senescence of human colon cancer cells treated with camptothecin. Author(s): Han Z, Wei W, Dunaway S, Darnowski JW, Calabresi P, Sedivy J, Hendrickson EA, Balan KV, Pantazis P, Wyche JH. Source: The Journal of Biological Chemistry. 2002 May 10; 277(19): 17154-60. Epub 2002 March 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11877436&dopt=Abstract
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Safe administration of irinotecan, oxaliplatin and raltitrexed in a DPD-deficient patient with metastatic colon cancer. Author(s): Volk J, Reinke F, van Kuilenburg AB, van Gennip AH, Schlichting C, Ganser A, Schoffski P. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2001 April; 12(4): 569-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11398894&dopt=Abstract
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Saponins-mediated potentiation of cisplatin accumulation and cytotoxicity in human colon cancer cells. Author(s): Gaidi G, Correia M, Chauffert B, Beltramo JL, Wagner H, Lacaille-Dubois MA. Source: Planta Medica. 2002 January; 68(1): 70-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11842333&dopt=Abstract
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Semimonthly versus monthly regimen of fluorouracil and leucovorin administered for 24 or 36 weeks as adjuvant therapy in stage II and III colon cancer: results of a randomized trial. Author(s): Andre T, Colin P, Louvet C, Gamelin E, Bouche O, Achille E, Colbert N, Boaziz C, Piedbois P, Tubiana-Mathieu N, Boutan-Laroze A, Flesch M, Buyse M, de Gramont A. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 August 1; 21(15): 2896-903. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885807&dopt=Abstract
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Stromal extracellular matrix reduces chemotherapy-induced apoptosis in colon cancer cell lines. Author(s): Kouniavsky G, Khaikin M, Zvibel I, Zippel D, Brill S, Halpern Z, Papa M. Source: Clinical & Experimental Metastasis. 2002; 19(1): 55-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918083&dopt=Abstract
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Systemic irinotecan or regional floxuridine chemotherapy prolongs survival after hepatic cryosurgery in patients with metastatic colon cancer refractory to 5fluorouracil. Author(s): Bilchik AJ, Wood TF, Chawla SP, Rose DM, Chung MH, Stern SS, Foshag LJ, Ramming KP. Source: Clin Colorectal Cancer. 2001 May; 1(1): 36-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445377&dopt=Abstract
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Targeting colon cancer cells with genistein-17.1A immunoconjugate. Author(s): Gentile MS, Vasu C, Green A, Murillo G, Das Gupta TK, Constantinou AI, Prabhakar BS, Salti GI. Source: International Journal of Oncology. 2003 May; 22(5): 955-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684659&dopt=Abstract
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Ternary combination of irinotecan, fluorouracil-folinic acid and oxaliplatin: results on human colon cancer cell lines. Author(s): Fischel JL, Rostagno P, Formento P, Dubreuil A, Etienne MC, Milano G. Source: British Journal of Cancer. 2001 February; 84(4): 579-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11207057&dopt=Abstract
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The activity profile of the hexacyclic camptothecin derivative DX-8951f in experimental human colon cancer and ovarian cancer. Author(s): van Hattum AH, Pinedo HM, Schluper HM, Erkelens CA, Tohgo A, Boven E. Source: Biochemical Pharmacology. 2002 October 15; 64(8): 1267-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234607&dopt=Abstract
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The cytotoxic effect of mistletoe lectins I, II and III on sensitive and multidrug resistant human colon cancer cell lines in vitro. Author(s): Valentiner U, Pfuller U, Baum C, Schumacher U. Source: Toxicology. 2002 February 28; 171(2-3): 187-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11836024&dopt=Abstract
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Toxicity and effects of adjuvant therapy in colon cancer: results of the German prospective, controlled randomized multicenter trial FOGT-1. Author(s): Staib L, Link KH, Beger HG; Members of the Forschungsgruppe Onkologie Gastrointestinaler Tumoren (FOGT).
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Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2001 May-June; 5(3): 275-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11419451&dopt=Abstract ·
Two unusual sites of colon cancer metastases and a rare thyroid lymphoma. Case 2. Chemotherapy-responsive right artial metastasis from colon carcinoma. Author(s): Choufani EB, Lazar HL, Hartshorn KL. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 August 1; 19(15): 3574-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11481366&dopt=Abstract
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Vaticanol C, a novel resveratrol tetramer, inhibits cell growth through induction of apoptosis in colon cancer cell lines. Author(s): Ito T, Akao Y, Tanaka T, Iinuma M, Nozawa Y. Source: Biological & Pharmaceutical Bulletin. 2002 January; 25(1): 147-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11824549&dopt=Abstract
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Vitamin D2 analog 19-nor-1,25-dihydroxyvitamin D2: antitumor activity against leukemia, myeloma, and colon cancer cells. Author(s): Kumagai T, O'Kelly J, Said JW, Koeffler HP. Source: Journal of the National Cancer Institute. 2003 June 18; 95(12): 896-905. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12813173&dopt=Abstract
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Weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) with folinic acid (FA) in adjuvant therapy of colon cancer. Author(s): Wein A, Riedel C, Bruckl W, Kastl S, Reingruber B, Hohenberger W, Hahn EG. Source: Zeitschrift Fur Gastroenterologie. 2001 February; 39(2): 153-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11253506&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: ·
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.comÒ: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDÒHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to colon cancer; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation (some Web sites are subscription based): ·
General Overview Breast Cancer Source: Healthnotes, Inc. www.healthnotes.com Breast Cancer Source: Integrative Medicine Communications; www.drkoop.com Cancer Prevention (Reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com Cancer Prevention and Diet Source: Healthnotes, Inc. www.healthnotes.com Colon Cancer Source: Healthnotes, Inc. www.healthnotes.com Colorectal cancer Source: Integrative Medicine Communications; www.drkoop.com Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Constipation Source: Healthnotes, Inc. www.healthnotes.com Crohn's Disease Source: Integrative Medicine Communications; www.drkoop.com Diverticular Disease Source: Integrative Medicine Communications; www.drkoop.com Immune Function Source: Healthnotes, Inc. www.healthnotes.com
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Inflammatory Bowel Disease Source: Integrative Medicine Communications; www.drkoop.com Iron-Deficiency Anemia Source: Healthnotes, Inc. www.healthnotes.com Lung Cancer Source: Healthnotes, Inc. www.healthnotes.com Menopause Source: Integrative Medicine Communications; www.drkoop.com Obesity Source: Integrative Medicine Communications; www.drkoop.com Ulcerative Colitis Source: Healthnotes, Inc. www.healthnotes.com Ulcerative Colitis Source: Integrative Medicine Communications; www.drkoop.com ·
Alternative Therapy Colon therapy Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,682,00.html Nutrition Source: Integrative Medicine Communications; www.drkoop.com
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Herbs and Supplements Acidophilus and Other Probiotics Source: Prima Communications, Inc.www.personalhealthzone.com Aminoglycosides Source: Integrative Medicine Communications; www.drkoop.com Antibiotic Combination: Sulfa Drugs Source: Integrative Medicine Communications; www.drkoop.com Barbiturates Source: Integrative Medicine Communications; www.drkoop.com Biguanides Source: Integrative Medicine Communications; www.drkoop.com Bile Acid Sequestrants Source: Integrative Medicine Communications; www.drkoop.com
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Calciferol Source: Integrative Medicine Communications; www.drkoop.com Calcitrol Source: Integrative Medicine Communications; www.drkoop.com Cephalosporins Source: Integrative Medicine Communications; www.drkoop.com Chemotherapy Source: Healthnotes, Inc. www.healthnotes.com Chitosan Source: Healthnotes, Inc. www.healthnotes.com Cholecalciferol Source: Integrative Medicine Communications; www.drkoop.com Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Cyclophosphamide Source: Healthnotes, Inc. www.healthnotes.com DHA Source: Integrative Medicine Communications; www.drkoop.com Docetaxel Source: Healthnotes, Inc. www.healthnotes.com Docosahexaenoic Acid Source: Healthnotes, Inc. www.healthnotes.com Docosahexaenoic Acid (DHA) Source: Integrative Medicine Communications; www.drkoop.com Echinacea Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Echinacea Alternative names: Echinacea angustifolia, Echinacea pallida, Echinacea purpurea, Purple Coneflower Source: Integrative Medicine Communications; www.drkoop.com Echinacea Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,775,00.html
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Echinacea angustifolia Source: Integrative Medicine Communications; www.drkoop.com Echinacea pallida Source: Integrative Medicine Communications; www.drkoop.com Echinacea purpurea Source: Integrative Medicine Communications; www.drkoop.com Eicosapentaenoic Acid (EPA) Source: Integrative Medicine Communications; www.drkoop.com Electrolytes Source: Integrative Medicine Communications; www.drkoop.com EPA Source: Integrative Medicine Communications; www.drkoop.com Erocalciferol Source: Integrative Medicine Communications; www.drkoop.com Fiber Source: Healthnotes, Inc. www.healthnotes.com Fiber Source: Integrative Medicine Communications; www.drkoop.com Fiber, insoluble Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,998,00.html Flavonoids Source: Healthnotes, Inc. www.healthnotes.com Fluorouracil Source: Healthnotes, Inc. www.healthnotes.com Glutamine Source: Integrative Medicine Communications; www.drkoop.com Glutathione Source: Healthnotes, Inc. www.healthnotes.com Greater Celandine Alternative names: Chelidonium majus Source: Healthnotes, Inc. www.healthnotes.com Green Tea Alternative names: Camellia sinensis Source: Healthnotes, Inc. www.healthnotes.com
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Histamine H2 Antagonists Source: Integrative Medicine Communications; www.drkoop.com Inhalant, Systemic, and Topical Corticosteroids Source: Integrative Medicine Communications; www.drkoop.com IP-6 Source: Healthnotes, Inc. www.healthnotes.com Ispaghula Source: Integrative Medicine Communications; www.drkoop.com Lycopene Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,803,00.html Macrolides Source: Integrative Medicine Communications; www.drkoop.com Melatonin Source: Healthnotes, Inc. www.healthnotes.com Methotrexate Source: Healthnotes, Inc. www.healthnotes.com Monophasic, Biphasic, and Triphasic Preparations Source: Integrative Medicine Communications; www.drkoop.com Musa Banana Alternative names: Plantain, Banana; Musa sp. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org N-Acetyl Cysteine Source: Healthnotes, Inc. www.healthnotes.com Paclitaxel Source: Healthnotes, Inc. www.healthnotes.com Penicillin Derivatives Source: Integrative Medicine Communications; www.drkoop.com Phosphorus Source: Integrative Medicine Communications; www.drkoop.com Plantago isphagula Source: Integrative Medicine Communications; www.drkoop.com Plantago psyllium Alternative names: Psyllium, Ispaghula; Plantago psyllium/ovata Source: Alternative Medicine Foundation, Inc. www.amfoundation.org
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Proton Pump Inhibitors (Gastric Acid Secretion Inhibitors) Source: Integrative Medicine Communications; www.drkoop.com Psyllium Alternative names: Ispaghula,Plantago isphagula Source: Integrative Medicine Communications; www.drkoop.com Purple Coneflower Source: Integrative Medicine Communications; www.drkoop.com Quinolones Source: Integrative Medicine Communications; www.drkoop.com Sambucus Alternative names: Black Elderberry; Sambucus nigra L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Stevia Alternative names: Sweetleaf; Stevia rebaudiana Bertoni Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Sulfasalazine Source: Healthnotes, Inc. www.healthnotes.com Sulindac Source: Healthnotes, Inc. www.healthnotes.com Tetracycline Derivatives Source: Integrative Medicine Communications; www.drkoop.com Uricosuric Agents Source: Integrative Medicine Communications; www.drkoop.com Zizyphus Alternative names: Jujube; Ziziphus sp. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON COLON CANCER Overview In this chapter, we will give you a bibliography on recent dissertations relating to colon cancer. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “colon cancer” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on colon cancer, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Colon Cancer ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to colon cancer. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: ·
A Personal Construct Analysis of Meaning Making in Remarkable Recovery from Advanced Colon Cancer by Allcroft, Kristine Davison; Phd from Fielding Graduate Institute, 2002, 379 pages http://wwwlib.umi.com/dissertations/fullcit/3072255
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An Investigation of the Relationship of Selected Dietary Factors and Colon Cancer by Wolczuk, Patricia Dianne; Phd from The University of British Columbia (canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK66846
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Beta-catenin and Tgf-beta Regulation of the Angiogenic Factor Fgf-bp1 in Colon Cancer by Ray, Ranjan; Phd from Georgetown University Medical Center, 2002, 140 pages http://wwwlib.umi.com/dissertations/fullcit/3077283
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Bile Acid Biological Activity in Colon Cancer Cells: from Hydrophobicity to Gene Activation by Powell, Ashley Ann; Phd from The University of Arizona, 2002, 180 pages http://wwwlib.umi.com/dissertations/fullcit/3053913
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Cancer-related Fatigue and Functional Status in Men and Women Receiving Chemotherapy for the Treatment of Lung or Colon Cancer by Warne, Catherine Paterson; Msn from Texas Tech University, 2002, 106 pages http://wwwlib.umi.com/dissertations/fullcit/1409783
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Combined Gene Transfer of Ifn-gamma-inducible Protein 10 (ip-10) and Interleukin12 Using First Generation Adenoviruses for Gene Therapy against Colon Cancer by Narvaiza Cuervas-mons, Inigo; Dr from Universidad De Navarra (spain), 2002, 220 pages http://wwwlib.umi.com/dissertations/fullcit/f225921
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Comparing Exact Tests and Asymptotic Tests with Colorectal Cancer Variables Within the National Health and Nutrition Examination Survey Iii by Musial, Joseph Leonard, Iii; Phd from Wayne State University, 1999, 60 pages http://wwwlib.umi.com/dissertations/fullcit/9954538
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Epidemiologic Studies of Coffee Consumption, Dietary Patterns, and Body Weight: Implications for Colorectal Cancer Prevention by Terry, Paul Daniel; Phd from Columbia University, 2002, 175 pages http://wwwlib.umi.com/dissertations/fullcit/3037763
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Genomics and Proteomics Based Approaches for the Development of New Diagnostic Reagents for Colon Cancer by Kelly, Kimberly Ann; Phd from The University of Utah, 2002, 140 pages http://wwwlib.umi.com/dissertations/fullcit/3067465
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Self-talk: Inner Work of Living with Colorectal Cancer by Will, Marilyn Dianne; Phd from University of Alberta (canada), 2002, 170 pages http://wwwlib.umi.com/dissertations/fullcit/NQ68639
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The Effects of Genetic and Luminal Risk Factors on Cyclooxygenase-2 Expression in Human Colon Cancer Cells by Parker, Michele Taylor; Phd from The University of Arizona, 2002, 158 pages http://wwwlib.umi.com/dissertations/fullcit/3050337
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The Risk for Colon Cancer and the Consumption of Ontario Sport Fish, Particularly Great Lake Sport Fish by Gibson, Debra Ann-marie; Msc from University of Toronto (canada), 2002, 115 pages http://wwwlib.umi.com/dissertations/fullcit/MQ73831
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The Role of Folate and Folylpoly-gamma-glutamate Synthetase (fpgs) in the Chemotherapeutics of Human Colon Cancer Cells by Smirnakis, Francesca F. Msc from University of Toronto (canada), 2002, 153 pages http://wwwlib.umi.com/dissertations/fullcit/MQ74123
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Use of Hmg Coa Reductase Inhibitors and the Risk of Colorectal Cancer by Bjork, Kathleen Pacitti; Phd from University of California, Irvine, 2002, 119 pages http://wwwlib.umi.com/dissertations/fullcit/3055400
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND COLON CANCER Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning colon cancer.
Recent Trials on Colon Cancer The following is a list of recent trials dedicated to colon cancer.8 Further information on a trial is available at the Web site indicated. ·
An Open Label Study of a Peptide Vaccine in Patients with Stage III Colon Cancer Condition(s): Colonic Neoplasms; Colorectal Neoplasms Study Status: This study is currently recruiting patients. Sponsor(s): Epimmune Purpose - Excerpt: EP2101 is a new cancer vaccine containing 10 different peptide antigens. The vaccine is designed to activate the immune system to develop a response against tumor cells in order to delay or prevent the recurrence of cancer. This study will test the safety and measure the level of immune stimulating capability of EP2101 in patients with Colon Cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00054912
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Antineoplaston Therapy in Treating Patients With Colon Cancer Condition(s): stage IV colon cancer; recurrent colon cancer; adenocarcinoma of the colon Study Status: This study is currently recruiting patients. Sponsor(s): Burzynski Research Institute
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These are listed at www.ClinicalTrials.gov.
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Purpose - Excerpt: RATIONALE: Antineoplastons are naturally occurring substances found in urine. Antineoplastons may inhibit the growth of cancer cells. PURPOSE: Phase II trial to study the effectiveness of antineoplaston therapy in treating patients with colon cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003486 ·
Antineoplaston Therapy in Treating Patients With Metastatic or Unresectable Colon Cancer Condition(s): stage IV colon cancer; recurrent colon cancer; adenocarcinoma of the colon Study Status: This study is currently recruiting patients. Sponsor(s): Burzynski Research Institute Purpose - Excerpt: RATIONALE: Antineoplastons are naturally occurring substances found in urine. Antineoplastons may inhibit the growth of cancer cells. PURPOSE: Phase II trial to study the effectiveness of antineoplaston therapy in treating patients with metastatic or unresectable colon cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003485
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Bevacizumab Plus Fluorouracil and Leucovorin in Treating Patients With Locally Advanced or Metastatic Colorectal Cancer That Has Progressed After Standard Chemotherapy Condition(s): Colon Cancer; Rectal Cancer Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Bevacizumab may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy such as fluorouracil and leucovorin use different ways to stop tumor cells from dividing so they stop growing or die. Combining bevacizumab with fluorouracil and leucovorin may kill more tumor cells. PURPOSE: Clinical trial to study the effectiveness of combining bevacizumab with fluorouracil and leucovorin in treating patients who have locally advanced or metastatic colorectal cancer that has progressed after standard chemotherapy. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00066846
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Capecitabine and Irinotecan in Treating Patients With Locally Advanced, Recurrent, or Metastatic Colorectal Cancer Condition(s): Colon Cancer; Rectal Cancer
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Study Status: This study is currently recruiting patients. Sponsor(s): Hoffmann-La Roche Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining capecitabine and irinotecan in treating patients who have locally advanced, recurrent, or metastatic colorectal cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00022698 ·
Combination Chemotherapy and Oblimersen in Treating Patients With Advanced Colorectal Cancer Condition(s): Colon Cancer; Rectal Cancer Study Status: This study is currently recruiting patients. Sponsor(s): San Antonio Cancer Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Oblimersen may increase the effectiveness of chemotherapy by making tumor cells more sensitive to the drugs. PURPOSE: Phase I/II trial to study the effectiveness of combining oxaliplatin, fluorouracil, and leucovorin with oblimersen in treating patients who have unresectable, metastatic, or recurrent colorectal cancer. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055822
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Combination Chemotherapy in Treating Patients With Colon Cancer Condition(s): adenocarcinoma of the colon; stage II colon cancer; stage III colon cancer Study Status: This study is currently recruiting patients. Sponsor(s): Groupe Regional d'Etudes du Cancer Colorectal Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which schedule of chemotherapy is most effective in treating colon cancer. PURPOSE: Randomized phase III trial to compare different schedules of chemotherapy using carboplatin with fluorouracil and leucovorin in treating patients who have stage IIB or stage III colon cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00046995
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Combination Chemotherapy in Treating Patients With Liver Metastases from Colorectal Cancer Condition(s): Colon Cancer; liver metastases; Rectal Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Cancer and Leukemia Group B; National Cancer Institute (NCI); Eastern Cooperative Oncology Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. It is not yet known which chemotherapy regimen is more effective for metastatic colorectal cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of intrahepatic floxuridine, leucovorin, and dexamethasone with that of systemic fluorouracil and leucovorin in treating patients who have unresectable liver metastases from colorectal cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002716
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Comparison of Barium Enema, Computed Tomographic Colonography, and Colonoscopy in Detecting Colon Cancer Condition(s): Colon Cancer; Rectal Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Duke Comprehensive Cancer Center Purpose - Excerpt: RATIONALE: Screening tests may help doctors detect cancer cells early and plan more effective treatment for cancer. New diagnostic procedures such as computed tomographic colonography may provide a less invasive method of identifying patients who have colon cancer. PURPOSE: Diagnostic and screening trial to compare the effectiveness of barium enema, computed tomographic colonography, and colonoscopy in detecting of colon cancer. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00016029
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Curcumin for the Prevention of Colon Cancer Condition(s): Colon Cancer Study Status: This study is currently recruiting patients. Sponsor(s): University of Michigan Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. Curcumin may be effective in preventing the development of colon cancer. PURPOSE: Phase I trial to determine the dose amount of curcumin that can be tolerated to help in preventing colon cancer in healthy men and women. Phase(s): Phase I
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00027495 ·
Erlotinib and Combination Chemotherapy in Treating Patients With Metastatic or Locally Advanced Colorectal Cancer Condition(s): Colon Cancer; Rectal Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Sidney Kimmel Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib with combination chemotherapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining erlotinib with fluorouracil, leucovorin, and oxaliplatin in treating patients who have metastatic or locally advanced colorectal cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00060411
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Gefitinib and Combination Chemotherapy in Treating Patients With Advanced Solid Tumors or Colorectal Cancer Condition(s): stage IV colon cancer; Stage IV rectal cancer; recurrent colon cancer; recurrent rectal cancer; adenocarcinoma of the colon; adenocarcinoma of the rectum Study Status: This study is currently recruiting patients. Sponsor(s): Stanford University; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Biological therapies such as gefitinib may interfere with the growth of tumor cells and slow the growth of the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug with gefitinib may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of gefitinib and oxaliplatin combined with leucovorin and fluorouracil in treating patients who have advanced solid tumors or colorectal cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025142
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Genetic Study of Familial Factors in Patients With Colon Cancer Condition(s): adenocarcinoma of the colon; stage I colon cancer; stage II colon cancer; stage III colon cancer; stage IV colon cancer Study Status: This study is currently recruiting patients.
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Sponsor(s): Cancer and Leukemia Group B; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Genetic studies may help in understanding the genetic processes involved in the development of some types of cancer. PURPOSE: Clinical trial to study the cancer-related genes in patients who have colon cancer or adenomatous polyps. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055848 ·
Genetic Study of Young Patients With Colorectal Cancer Condition(s): Colon Cancer; hereditary non-polyposis colon cancer (hMSH2, hMLH1, hPMS1, hPMS2); Rectal Cancer Study Status: This study is currently recruiting patients. Sponsor(s): American College of Surgeons; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Identifying gene mutations (microsatellite instability) may allow doctors to plan effective treatment for patients who develop colorectal cancer at an early age. PURPOSE: Genetic trial to determine the significance of gene mutations in helping predict the outcome of treatment in patients who develop stage I, stage II, or stage III colorectal cancer at an early age. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044967
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Genetic Trial to Study Diarrhea in Patients With Stage III Colon Cancer Who Are Receiving Chemotherapy Condition(s): adenocarcinoma of the colon; stage III colon cancer; Diarrhea; Neutropenia Study Status: This study is currently recruiting patients. Sponsor(s): Cancer and Leukemia Group B; National Cancer Institute (NCI); North Central Cancer Treatment Group Purpose - Excerpt: RATIONALE: Genetic testing may help predict how patients will respond to chemotherapy drugs and may help doctors plan more effective treatment with fewer side effects. PURPOSE: Genetic study to determine how genes affect the severity of diarrhea in patients with stage III colon cancer who are receiving chemotherapy. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048971
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High-Dose Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Advanced Cancer Condition(s): Ewing's family of tumors; Ewing's sarcoma and primitive neuroepithelial tumor; Wilms' tumor and other childhood kidney tumors; Anal Cancer; Breast Cancer; Colorectal Cancer; Esophageal Cancer; extrahepatic bile duct cancer; Gallbladder Cancer; Gastric Cancer; liver and intrahepatic biliary tract cancer; Melanoma; Muscle
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Cancer; Osteosarcoma; ovarian epithelial cancer; Pancreatic Cancer; small intestine cancer Study Status: This study is currently recruiting patients. Sponsor(s): Beckman Research Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation in treating patients who have advanced cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002854 ·
High-Dose Fluorouracil With or Without Leucovorin Compared With Standard Fluorouracil Plus Leucovorin Following Surgery in Treating Patients With Stage III Colon Cancer Condition(s): stage III colon cancer; adenocarcinoma of the colon; mucinous adenocarcinoma of the colon Study Status: This study is currently recruiting patients. Sponsor(s): Robert Roessle Klinik; EORTC Gastrointestinal Tract Cancer Cooperative Group; Federation Francophone de Cancerologie Digestive; Grupo Espanol Tratamiento Tumores Digestivos Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which chemotherapy regimen is more effective for colon cancer. PURPOSE: Randomized phase III trial to study the effectiveness of high-dose fluorouracil with or without leucovorin compared with standard-dose fluorouracil plus leucovorin following surgery in treating patients who have stage III colon cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004150
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Immunotherapy After Surgery in Treating Patients With Breast Cancer, Colon Cancer, or Melanoma Condition(s): Breast Cancer; Colon Cancer; Melanoma; recurrent breast cancer Study Status: This study is currently recruiting patients. Sponsor(s): Centro Oncologico de Excelencia Purpose - Excerpt: RATIONALE: Immunotherapy uses different ways to stimulate the immune system and stop cancer cells from growing. Immunotherapy biological extracts may be useful as adjuvant therapy in treating patients who have had surgery for breast cancer, colon cancer, or melanoma. PURPOSE: Phase III trial to study the effectiveness
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of Corynebacterium granulosum extract as maintenance immunotherapy following surgery in treating patients with breast cancer, colon cancer, or melanoma. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002455 ·
Irinotecan Compared With Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer Condition(s): Colon Cancer; Rectal Cancer Study Status: This study is currently recruiting patients. Sponsor(s): North Central Cancer Treatment Group; National Cancer Institute (NCI); Southwest Oncology Group; Eastern Cooperative Oncology Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective for colorectal cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of irinotecan with that of combination chemotherapy in treating patients who have advanced colorectal cancer that has not responded to previous treatment. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005036
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LMB-9 Immunotoxin in Treating Patients With Advanced Pancreatic, Esophageal, Stomach, Colon, or Rectal Cancer Condition(s): Colorectal Cancer; Esophageal Cancer; Gastric Cancer; Pancreatic Cancer Study Status: This study is currently recruiting patients. Sponsor(s): University of Freiburg; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: LMB-9 immunotoxin can locate tumor cells and kill them without harming normal cells. This may be an effective treatment for advanced pancreatic, esophageal, stomach, colon or rectal cancer. PURPOSE: Phase I trial to study the effectiveness of LMB-9 immunotoxin in treating patients who have advanced pancreatic, esophageal, stomach, colon, or rectal cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00010270
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Monoclonal Antibody Therapy and/or Vaccine Therapy in Treating Patients With Locally Advanced or Metastatic Colorectal Cancer Condition(s): Colon Cancer; Rectal Cancer
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Study Status: This study is currently recruiting patients. Sponsor(s): Onyvax Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Vaccines made from cancer cells may make the body build an immune response to kill colorectal tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of monoclonal antibody therapy and/or vaccine therapy in treating patients who have locally advanced or metastatic colorectal cancer. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00007826 ·
Monoclonal Antibody Therapy in Treating Patients With Lymphoma, Colon Cancer, or Prostate Cancer That Has Not Responded to Vaccine Therapy Condition(s): recurrent grade I follicular small cleaved cell lymphoma; recurrent grade II follicular mixed cell lymphoma; recurrent grade III follicular large cell lymphoma; recurrent colon cancer; recurrent prostate cancer; recurrent mantle cell lymphoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Monoclonal antibodies such as anti-cytotoxic Tlymphocyte-associated antigen-4 can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. PURPOSE: Phase II trial to study the effectiveness of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody in treating patients who have lymphoma, colon cancer, or prostate cancer that has not responded to vaccine therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047164
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Oxaliplatin, Fluorouracil, and Leucovorin With or Without PTK787/ZK 222584 in Treating Patients With Refractory or Recurrent Metastatic Colon or Rectal Cancer Condition(s): adenocarcinoma of the rectum; adenocarcinoma of the colon; stage IV colon cancer; recurrent colon cancer; Stage IV rectal cancer; recurrent rectal cancer Study Status: This study is currently recruiting patients. Sponsor(s): Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, fluorouracil, and leucovorin, use different ways to stop tumor cells from dividing so they stop growing or die. PTK787/ZK 222584 may stop the growth of tumor cells by stopping blood flow to the tumor. It is not yet known whether combination chemotherapy is more effective with or without PTK787/ZK 222584 in treating colon or rectal cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of combining oxaliplatin, fluorouracil, and leucovorin with or without PTK787/ZK 222584 in treating patients who have refractory or recurrent metastatic colon or rectal cancer.
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Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00068679 ·
Vaccine Therapy in Treating Patients With Cancer of the Gastrointestinal Tract Condition(s): Gastrointestinal Cancer Study Status: This study is currently recruiting patients. Sponsor(s): University of Texas; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. PURPOSE: Randomized phase II trial to compare the effectiveness of two different vaccines in treating patients who have cancer of the gastrointestinal tract. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012246
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Vaccine Therapy in Treating Patients With Stage II or Stage III Colon Cancer That has Been Removed During Surgery Condition(s): stage II colon cancer; stage III colon cancer; adenocarcinoma of the colon Study Status: This study is currently recruiting patients. Sponsor(s): Intracel Purpose - Excerpt: RATIONALE: Vaccines made from a patient's white blood cells and tumor cells may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining vaccine therapy with chemotherapy may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy combined with leucovorin and fluorouracil in treating patients who have undergone surgery to completely remove stage II or stage III colon cancer. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00016133
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BMS-247550 in Treating Patients With Recurrent or Metastatic Colorectal Cancer Condition(s): recurrent colon cancer; adenocarcinoma of the rectum; Stage IV rectal cancer; recurrent rectal cancer; stage IV colon cancer; adenocarcinoma of the colon Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); University of Chicago Cancer Research Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to
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study the effectiveness of BMS-247550 in treating patients who have recurrent or metastatic colorectal cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00022477 ·
Combination Chemotherapy With or Without Bevacizumab Compared With Bevacizumab Alone in Treating Patients With Advanced or Metastatic Colorectal Cancer That Has Been Previously Treated Condition(s): stage III colon cancer; stage IV colon cancer; stage III rectal cancer; Stage IV rectal cancer; recurrent colon cancer; recurrent rectal cancer; adenocarcinoma of the colon; adenocarcinoma of the rectum Study Status: This study is no longer recruiting patients. Sponsor(s): Eastern Cooperative Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as bevacizumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with combination chemotherapy may kill more tumor cells. It is not yet known if bevacizumab is more effective with or without combination chemotherapy in treating colorectal cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without bevacizumab in treating patients who have advanced or metastatic colorectal cancer that has been previously treated. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025337
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Combination Chemotherapy With or Without Irinotecan in Treating Patients With Stage III Colon Cancer Condition(s): stage III colon cancer; adenocarcinoma of the colon Study Status: This study is no longer recruiting patients. Sponsor(s): Federation Nationale des Centres de Lutte Contre le Cancer; Federation Francophone de Cancerologie Digestive Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known if combination chemotherapy is more effective with or without irinotecan in treating colon cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without irinotecan in treating patients who have stage III colon cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below
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Web Site: http://clinicaltrials.gov/ct/show/NCT00005979 ·
Endoscopic Placement of Metal Stent in Patients With Cancer-Related Bowel Obstruction Condition(s): Gastric Cancer; Colorectal Cancer; Colon Cancer; Rectal Cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Robert H. Lurie Cancer Center Purpose - Excerpt: RATIONALE: The use of endoscopy to place a metal stent in the large intestine is less invasive than surgery for treating cancer-related bowel obstruction and may have fewer side effects and improve recovery. PURPOSE: Phase I/II trial to study the effectiveness of endoscopic placement of a metal stent in treating patients who have cancer-related bowel obstruction. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004911
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Endoscopic Placement of Metal Stents in Treating Patients With Cancer- Related Duodenal Obstruction Condition(s): Pancreatic Cancer; Gastric Cancer; Colorectal Cancer; Colon Cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Robert H. Lurie Cancer Center Purpose - Excerpt: RATIONALE: The use of endoscopy to place metal stents in the duodenum is less invasive than surgery for treating cancer-related duodenal obstruction and may have fewer side effects and improve recovery. PURPOSE: Phase I/II trial to study the effectiveness of endoscopic placement of metal stents in treating patients who have cancer-related obstruction of the duodenum. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004910
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Exisulind in Preventing Polyps in Patients With Familial Adenomatous Polyposis Condition(s): Colon Cancer; Rectal Cancer; small intestine cancer Study Status: This study is no longer recruiting patients. Sponsor(s): Huntsman Cancer Institute Purpose - Excerpt: RATIONALE: Exisulind may be effective in preventing the development and growth of polyps in patients who have familial adenomatous polyposis. PURPOSE: Randomized phase II/III trial to determine the effectiveness of exisulind in preventing the development and growth of polyps in patients who have familial adenomatous polyposis. Phase(s): Phase II; Phase III Study Type: Interventional
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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00026468 ·
Fluorouracil and Leucovorin With or Without Irinotecan in Treating Patients Following Surgery for Stage III Colorectal Cancer Condition(s): adenocarcinoma of the rectum; stage III colon cancer; stage III rectal cancer; adenocarcinoma of the colon Study Status: This study is no longer recruiting patients. Sponsor(s): Rhone Poulenc Rorer S.A. Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them after surgery may kill more tumor cells. PURPOSE: Randomized phase III trial to compare the effectiveness of fluorouracil and leucovorin with or without irinotecan in treating patients who have undergone surgery for stage III colorectal cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00026273
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Fluorouracil Plus Leucovorin With or Without Oxaliplatin in Treating Patients With Stage II or Stage III Colon Cancer Condition(s): stage III colon cancer; stage II colon cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); National Surgical Adjuvant Breast and Bowel Project (NSABP) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective for colon cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of fluorouracil plus leucovorin with or without oxaliplatin in treating patients who have stage II or stage III colon cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004931
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Gene Testing in Patients With Colon Cancer Condition(s): stage III colon cancer; adenocarcinoma of the colon Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Cancer and Leukemia Group B Purpose - Excerpt: RATIONALE: Analyzing the structure of genes found in a person's cancer cells may help doctors improve methods of treating patients with colon cancer.
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PURPOSE: Clinical trial to study the genes of patients treated with chemotherapy for colon cancer. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003571 ·
Gene Therapy in Patients With Colon Cancer That Has Spread to the Liver Condition(s): recurrent colon cancer; liver metastases; stage IV colon cancer; adenocarcinoma of the colon Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Gene therapy may make the body build an immune response to kill tumor cells. PURPOSE: Phase I trial to study the safety of NV1020 in patients who have colon cancer that has spread to the liver and has not responded to previous chemotherapy. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012155
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Genetic Study in Patients With Stage II or Stage III Colon Cancer Condition(s): stage II colon cancer; stage III colon cancer; adenocarcinoma of the colon Study Status: This study is no longer recruiting patients. Sponsor(s): North Central Cancer Treatment Group; National Cancer Institute (NCI); National Cancer Institute of Canada Purpose - Excerpt: RATIONALE: Genetic studies may help in understanding the genetic processes that cause some types of cancer. PURPOSE: Genetic trial to study certain genes of patients who have stage II or stage III colon cancer. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003833
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Laparoscopic-Assisted Surgery Compared With Open Surgery in Treating Patients With Colon Cancer Condition(s): stage III colon cancer; stage I colon cancer; adenocarcinoma of the colon; stage II colon cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Southwest Oncology Group; Eastern Cooperative Oncology Group; Radiation Therapy Oncology Group; Cancer and Leukemia Group B; National Cancer Institute of Canada; National Surgical Adjuvant Breast and Bowel Project (NSABP); North Central Cancer Treatment Group Purpose - Excerpt: RATIONALE: Less invasive types of surgery may help reduce the number of side effects and improve recovery. It is not yet known which type of surgery
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is more effective for colon cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of laparoscopic-assisted colectomy with open colectomy in treating patients who have colon cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002575 ·
Monoclonal Antibody Therapy Compared With No Further Therapy After Surgery in Treating Patients With Stage II Colon Cancer Condition(s): stage II colon cancer; adenocarcinoma of the colon Study Status: This study is no longer recruiting patients. Sponsor(s): Cancer and Leukemia Group B; National Cancer Institute (NCI); Southwest Oncology Group; Eastern Cooperative Oncology Group; North Central Cancer Treatment Group; EORTC Gastrointestinal Tract Cancer Cooperative Group; National Cancer Institute of Canada Purpose - Excerpt: RATIONALE: Monoclonal antibodies such as edrecolomab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether surgery to remove colon cancer is more effect with or without monoclonal antibody therapy. PURPOSE: Randomized phase III trial to compare the effectiveness of surgery with or without monoclonal antibody therapy in treating patients who have stage II colon cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002968
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Oxaliplatin in Treating Patients With Previously Treated Locally Advanced or Metastatic Colorectal Cancer Condition(s): recurrent colon cancer; adenocarcinoma of the rectum; stage III colon cancer; stage III rectal cancer; Stage IV rectal cancer; recurrent rectal cancer; stage IV colon cancer; adenocarcinoma of the colon Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Roswell Park Cancer Institute Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Clinical trial to study the effectiveness of oxaliplatin in treating patients who have locally advanced or metastatic colorectal cancer that has been previously treated. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00040820
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ZD 1839 in Treating Patients With Locally Advanced or Metastatic Colorectal Cancer That Has Not Responded to Chemotherapy Condition(s): recurrent colon cancer; adenocarcinoma of the rectum; stage III colon cancer; stage III rectal cancer; Stage IV rectal cancer; recurrent rectal cancer; stage IV colon cancer; adenocarcinoma of the colon Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); University of Texas Purpose - Excerpt: RATIONALE: Biological therapies such as ZD 1839 may interfere with the growth of tumor cells and slow the growth of colorectal cancer. PURPOSE: Phase II trial to study the effectiveness of ZD 1839 in treating patients who have locally advanced or metastatic colorectal cancer that has not responded to fluorouracil and irinotecan. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00030524
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ZD 1839 Plus Combination Chemotherapy in Treating Patients With Locally Advanced, Locally Recurrent, or Metastatic Colorectal Cancer Condition(s): recurrent colon cancer; adenocarcinoma of the rectum; Stage IV rectal cancer; recurrent rectal cancer; stage IV colon cancer; adenocarcinoma of the colon Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Dana-Farber/Harvard Cancer Center Purpose - Excerpt: RATIONALE: Biological therapies such as ZD 1839 may interfere with the growth of tumor cells and slow the growth of the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining ZD 1839 with combination chemotherapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of ZD 1839 combined with irinotecan, leucovorin, and fluorouracil in treating patients who have locally advanced, locally recurrent, or metastatic colorectal cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00026364
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Acupuncture to prevent postoperative bowel paralysis (paralytic ileus) Condition(s): Colostomy; Ileostomy; Bowel Cancer; Postoperative Paralytic Ileus Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: The purpose of this study is to determine if acupuncture is effective in preventing prolonged postoperative paralysis of the gastrointestinal tract among patients undergoing colostomy/ileostomy closure. Phase(s): Phase II
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065234 ·
BMS-247550 in Treating Patients With Metastatic Colorectal Cancer Condition(s): recurrent colon cancer; adenocarcinoma of the rectum; Stage IV rectal cancer; recurrent rectal cancer; stage IV colon cancer; adenocarcinoma of the colon Study Status: This study is suspended. Sponsor(s): National Cancer Institute (NCI); UAB Comprehensive Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of BMS-247550 in treating patients who have metastatic colorectal cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033306
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Combination Chemotherapy in Treating Patients With Colorectal Cancer Condition(s): recurrent colon cancer; adenocarcinoma of the rectum; stage III colon cancer; stage III rectal cancer; Stage IV rectal cancer; recurrent rectal cancer; stage IV colon cancer; adenocarcinoma of the colon Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI); Eastern Cooperative Oncology Group; Cancer and Leukemia Group B Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if the effectiveness of irinotecan combined with fluorouracil in treating colorectal cancer varies depending on the patient's racial background. PURPOSE: Phase III trial to study the effectiveness of irinotecan combined with fluorouracil in treating patients from different racial backgrounds who have colorectal cancer that is advanced, recurrent, metastatic or has not responded to treatment with fluorouracil. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006103
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Combination Chemotherapy With or Without Chemoembolization in Treating Patients With Colorectal Cancer Metastatic to the Liver Condition(s): recurrent colon cancer; adenocarcinoma of the rectum; liver metastases; Stage IV rectal cancer; recurrent rectal cancer; stage IV colon cancer; adenocarcinoma of the colon Study Status: This study is suspended.
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Sponsor(s): National Cancer Institute (NCI); American College of Radiology Imaging Network Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. One way to give chemotherapy drugs is by chemoembolization, which kills tumor cells by delivering drugs directly into the tumor and then blocking the blood flow to the tumor. It is not yet known if chemoembolization is more effective than standard chemotherapy in treating metastatic cancer. PURPOSE: Phase I trial and randomized phase III trial to determine the effectiveness of chemoembolization in treating patients who have colorectal cancer metastatic to the liver. For the phase III part of the trial, patients will be randomly assigned to one of two groups. Patients in group one will receive chemotherapy once a week for 4 weeks. Treatment may be repeated every 6 weeks for as long as benefit is shown. Patients in group two will receive chemotherapy as in group one and will undergo chemoembolization on day 36. The chemotherapy may be repeated as in group one. Chemoembolization may be repeated every 6 weeks for up to four courses. Patients will be evaluated every 3 months for 2 years, every 6 months for 3 years, and once a year thereafter. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023868 ·
Immunotherapy in Treating Patients With Resected Liver Metastases From Colon Cancer Condition(s): liver metastases; stage IV colon cancer Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI); Duke Comprehensive Cancer Center Purpose - Excerpt: RATIONALE: Immunotherapy using CEA -treated white blood cells may help a person's body build an immune response to kill their tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of immunotherapy with CEA-treated white blood cells in treating patients with resected liver metastases from colon cancer. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003433
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Octreotide as Palliative Therapy for Cancer-Related Bowel Obstruction That Cannot Be Removed by Surgery Condition(s): Pancreatic Cancer; Gastric Cancer; Colorectal Cancer; ovarian epithelial cancer; Colon Cancer; Rectal Cancer Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI); Robert H. Lurie Cancer Center Purpose - Excerpt: RATIONALE: Palliative therapy with octreotide may help patients who have bowel obstruction that cannot be removed by surgery to live longer and more comfortably. PURPOSE: Phase II trial to study the effectiveness of octreotide as
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palliative therapy in treating patients who have cancer-related bowel obstruction that cannot be removed by surgery. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004895 ·
Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Recurrent or Persistent Colorectal Cancer Condition(s): recurrent colon cancer; adenocarcinoma of the rectum; Stage IV rectal cancer; recurrent rectal cancer; stage IV colon cancer; adenocarcinoma of the colon Study Status: This study is suspended. Sponsor(s): National Cancer Institute (NCI); UAB Comprehensive Cancer Center Purpose - Excerpt: RATIONALE: Radiolabeled monoclonal antibodies can locate tumor cells and deliver tumor-killing substances to them without harming normal cells. Radiolabeled monoclonal antibody therapy may be effective treatment for colorectal cancer. PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody therapy in treating patients who have recurrent or persistent colorectal cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023933
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SU5416 and Irinotecan in Treating Patients With Advanced Colorectal Cancer Condition(s): recurrent colon cancer; adenocarcinoma of the rectum; stage III colon cancer; stage III rectal cancer; Stage IV rectal cancer; recurrent rectal cancer; stage IV colon cancer; adenocarcinoma of the colon Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI); M.D. Anderson Cancer Center Purpose - Excerpt: RATIONALE: SU5416 may stop the growth of colorectal cancer by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I/II trial to study the effectiveness of combining SU5416 and irinotecan in treating patients who have advanced colorectal cancer. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005818
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Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “colon cancer” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: ·
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON COLON CANCER Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “colon cancer” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on colon cancer, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Colon Cancer By performing a patent search focusing on colon cancer, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on colon cancer: ·
4-(4'-hydroxyphenyl) amino-6,7-dimethoxyquinazoline to prevent development of colorectal cancer Inventor(s): Uckun; Fatih M. (White Bear Lake, MN) Assignee(s): Parker Hughes Institute (Roseville, MN) Patent Number: 6,482,828 Date filed: May 14, 2002 Abstract: The present invention is directed to a method of preventing the development or recurrence of colorectal cancer in a mammal comprising administering to the mammal, an effective cancer preventative amount of 4-(4'-hydroxyphenyl)-amino-6,7dimethoxyquinazoline or a pharmaceutically acceptable salt thereof. Excerpt(s): The present invention relates to quinazoline compounds, compositions and therapeutic methods for the treatment of cancers by administering quinazoline compounds.... Currently, there is a need for methods useful for preventing the development or recurrence of cancer in mammals. Quinazoline compounds have been suggested as useful compounds in the treatment of cell growth and differentiation characterized by activity of the human epidermal growth factor receptor type2 (HER2). See, for example, Myers et.al., U.S. Pat. No. 5,721,237. Some quinazoline derivatives have been suggested as useful as anti-cancer agents for the treatment of specific receptor tyrosine kinase-expressing cancers, especially those expressing epithelial growth factor (EGF) receptor tyrosine kinase. See, for example, Barker et. al., U.S. Pat. No. 5,457,105. It is generally taught that quinazolines exert their anti-tumor effects via tyrosine kinase inhibition. However, while some quinazoline compounds inhibit the growth of tumor cells, such as brain tumor cells, others with equally potent tyrosine kinase inhibitory activity fail to do so (Naria et.al., 1998, Clin. Cancer Res. 4:1405-1414; Naria et.al., 1998, Clin. Cancer Res. 4:2463-2471).... Some quinazoline derivatives have also been suggested as useful agents for treating precancerous legions and inhibiting the growth of neoplastic cells. See for example, Pamukeu et al., U.S. Pat. Nos. 5,990,117; 6,037,345; and 6,046,206. Although many of the disclosed quinazoline derivatives are useful for treating precancerous legions and inhibiting the growth of neoplastic cells, there still exists the need to discover better compounds for the treatment of cancer, in particular colorectal cancer. Web site: http://www.delphion.com/details?pn=US06482828__
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Chromosome 18Q loss and prognosis in colorectal cancer Inventor(s): Hamilton; Stanley (Lutherville, MD), Kinzler; Kenneth W. (Baltimore, MD), Vogelstein; Bert (Baltimore, MD) Assignee(s): The Johns Hopkins Unviersity (Baltimore, MD) Patent Number: 5,834,190 Date filed: January 29, 1996 Abstract: To examine the status of chromosome 18q, polymorphic genetic markers and DNA from formalin-fixed, paraffin-embedded tumors are employed. DNA from normal
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tissue is used as a comparison. The status of chromosome 18q is prognostic of the survival among stage II and stage III colorectal cancer patients. Excerpt(s): This invention was partially supported by grants (CA-35494, CA-47527, and CA-62924) from the National Cancer Institute. The U.S. government retains certain rights in this invention.... With about 150,000 cases and 60,000 deaths annually, colorectal cancer is one of the commonest causes of death from cancer in the United States. Currently, determining prognosis and selecting patients for postoperative adjuvant therapy rely mainly on pathological and clinical staging..sup.2,3 The TNM system--T for primary tumor, N for regional lymph node involvement, and M for metastases--developed by the Union Internationale Contre Cancer (UICC) is one of the two major staging systems currently in use. Patients with TNM stage I cancer (Dukes stage A: tumor confined within the bowel wall, with no lymph-node metastasis) usually have a normal life span, whereas patients with stage IV disseminated disease have a very poor survival rate. However, predicting outcome in patients with intermediate stages is difficult. Patients with stage II colorectal cancer (Dukes' stage B: tumor extending through the bowel wall, without lymph-node metastasis) have a five-year survival rate of about 70 percent, and those with stage III disease (Dukes' stage C: regional lymph-node metastasis) have a rate of only 40 to 50 percent..sup.4 Adjuvant therapy improves the outcome in subgroups of patients, but it leads to substantial morbidity..sup.5-9 Better means of formulating the prognosis in patients with colorectal cancer would improve the selection of patients for adjuvant chemotherapy and radiation therapy.... Colorectal cancers result from the accumulation of several distinct genetic alterations involving the K-ras oncogene on chromosome 12 and tumor-suppressor genes on chromosomes 5, 17, and 18..sup.10-12 The short arm of chromosome 17 (17p) and the long arm of chromosome 18 (18q) are frequently lost in colorectal tumors. This observation led to the discovery that inactivation of the p53 and DCC gene (located on chromosomes 17p and 18q, respectively) probably contributes to the neoplastic transformation of colorectal epithelial cells..sup.3,4 Although studies of the biochemical mechanisms underlying the development of colorectal cancer are just beginning, the genes involved in this process have the potential to serve as markers in diagnosis and prognosis. Web site: http://www.delphion.com/details?pn=US05834190__ ·
Colon cancer marker Inventor(s): Baughn; Mariah R. (San Leandro, CA), Krasnow; Randi E. (Stanford, CA), Wolven; Amy K. (Oakland, CA), Warren; Bridget A. (Cupertino, CA) Assignee(s): Incyte Genomics, Inc. (Palo Alto, CA) Patent Number: 6,448,041 Date filed: December 18, 2000 Abstract: The invention provides a cDNA which encodes a colon cancer marker. It also provides for the use of the cDNA, fragments, complements, and variants thereof and of the encoded protein, portions thereof and antibodies thereto for diagnosis and treatment of colon disorders, particularly colon cancer and polyps. The invention additionally provides expression vectors and host cells for the production of the protein and a transgenic model system. Excerpt(s): This invention relates to a mammalian cDNA which encodes a colon cancer marker and to the use of the cDNA and the encoded protein in the diagnosis and
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treatment of colon disorders, particularly colon cancer and polyps.... Phylogenetic relationships among organisms have been demonstrated many times, and studies from a diversity of prokaryotic and eukaryotic organisms suggest a more or less gradual evolution of molecules, biochemical and physiological mechanisms, and metabolic pathways. Despite different evolutionary pressures, the proteins of nematode, fly, rat, and man have common chemical and structural features and generally perform the same cellular function. Comparisons of the nucleic acid and protein sequences from organisms where structure and/or function are known accelerate the investigation of human sequences and allow the development of model systems for testing diagnostic and therapeutic agents for human conditions, diseases, and disorders.... Colorectal cancer is the fourth most common cancer and the second most common cause of cancer death in the United States with approximately 130,000 new cases and 55,000 deaths per year. Colon and rectal cancers share many environmental risk factors and both are found in individuals with specific genetic syndromes (Potter (1999) J Natl Cancer Institute 91:916-932). Colon cancer is the only cancer that occurs with approximately equal frequency in men and women, and the five-year survival rate following diagnosis of colon cancer is around 55% in the United States (Ries et al. (1990) National Institutes of Health, DHHS Publ. No. (NI)90-2789). Web site: http://www.delphion.com/details?pn=US06448041__ ·
Colorectal chemoprotective composition and method of preventing colorectal cancer Inventor(s): McCracken; John D. (Redlands, CA), Wechter; William J. (Redlands, CA) Assignee(s): Loma Linda University Medical Center (Loma Linda, CA) Patent Number: 5,955,504 Date filed: March 13, 1995 Abstract: A composition for use in preventing colorectal cancer and other neoplastic diseases includes an enantiomerically stable R-NSAID or a pharmaceutically acceptable salt thereof in an amount effective to elicit a chemoprotective effect. The composition is substantially free of the S-enantiomer of the R-NSAID. Therapeutic use of the composition is accompanied by reduced adverse side effects. Excerpt(s): The present invention relates to compositions and methods useful in the prevention of colorectal and other gastrointestinal epithelial cancers.... Cancer of the colon is common in the western world and is an important cause of morbidity and mortality, having an incidence of about 5% in the U.S. population. As with other types of cancers, cancers of the gastrointestinal tract, including colon cancer, are characterized by abnormal development in cell proliferation and differentiation in the gastrointestinal tract.... The gastrointestinal tract, including the rectum and colon, is lined with epithelial cells which have a high proliferation rate. The lining of the colon, in particular, made up of columnar rows of epithelial cells, is characterized by a series of indentations or crypts. Epithelial cells in the bottom regions of the crypts proliferate and move upward toward the tops of the crypts. In the normal colon, the proliferation region of the large intestine normally occupies the basal or deeper three-quarters of the crypts. A relationship has been observed between the expansion of cell proliferation zones to the upper regions of the crypts and colon cancer. See M. Lipkin, "Biomarkers of Increased Susceptibility to Gastrointestinal Cancer: New Application to Studies of Cancer Prevention in Human Subjects," Cancer Research, Vol. 48, pp. 235-245 (Jan. 15, 1988). Web site: http://www.delphion.com/details?pn=US05955504__
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Compositions that specifically bind to colorectal cancer cells and methods of using the same Inventor(s): Waldman; Scott A. (Ardmore, PA) Assignee(s): Thomas Jefferson University (Philadelphia, PA) Patent Number: 6,087,109 Date filed: November 17, 1998 Abstract: Conjugated compounds that comprise an ST receptor binding moiety and an active moiety that is an antisense molecule are disclosed. Pharmaceutical compositions which comprise conjugated compounds that comprise an ST receptor binding moiety and an active moiety that is an antisense molecule are disclosed including pharmaceutical compositions that have enteric formulations. Methods of treating an individual suspected of suffering from colorectal cancer and methods of preventing colorectal cancer are disclosed. Excerpt(s): The present invention relates to conjugated compounds which comprise an St receptor ligand moiety conjugated to an active moiety which is an antisense molecule. ST receptor binding moieties bind to the ST receptor which is found on human colon cells. The invention relates to antisense compositions specifically targeted to colon cells. The invention relates to methods of treating and preventing colorectal tumors.... Colorectal cancer is the third most common neoplasm worldwide. The mortality rate of newly diagnosed large bowel cancer approaches 50% and there has been little improvement over the past 40 years. Most of this mortality reflects local, regional and distant metastases.... Surgery is the mainstay of treatment for colorectal cancer but recurrence is frequent. Colorectal cancer has proven resistant to chemotherapy, although limited success has been achieved using a combination of 5-fluorouracil and levamisole. Surgery has had the largest impact on survival and, in some patients with limited disease, achieves a cure. However, surgery removes bulk tumor, leaving behind microscopic residual disease which ultimately results in recrudescence. Web site: http://www.delphion.com/details?pn=US06087109__
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Compounds for immunotherapy and diagnosis of colon cancer and methods for their use Inventor(s): Xu; Jiangchun (Bellevue, WA) Assignee(s): Corixa Corporation (Seattle, WA) Patent Number: 6,284,241 Date filed: December 23, 1998 Abstract: Compounds and methods for the treatment and diagnosis of colon cancer are provided. The inventive compounds include polypeptides containing at least a portion of a colon tumor protein. Vaccines and pharmaceutical compositions for immunotherapy of colon cancer comprising such polypeptides, or polynucleotide molecules encoding such polypeptides, are also provided, together with DNA molecules for preparing the inventive polypeptides. Excerpt(s): The present invention relates generally to compositions and methods for the treatment and diagnosis of colon cancer. The invention is more specifically related to
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nucleotide sequences that are preferentially expressed in colon tumor tissue, together with polypeptides encoded by such nucleotide sequences. The inventive nucleotide sequences and polypeptides may be used in vaccines and pharmaceutical compositions for the treatment and diagnosis of colon cancer.... Colon cancer is the second most frequently diagnosed malignancy in the United States as well as the second most common cause of cancer death. An estimated 95,600 new cases of colon cancer will be diagnosed in 1998, with an estimated 47,700 deaths. The five-year survival rate for patients with colorectal cancer detected in an early localized stage is 92%; unfortunately, only 37% of colorectal cancer is diagnosed at this stage. The survival rate drops to 64% if the cancer is allowed to spread to adjacent organs or lymph nodes, and to 7% in patients with distant metastases.... The prognosis of colon cancer is directly related to the degree of penetration of the tumor through the bowel wall and the presence or absence of nodal involvement, consequently, early detection and treatment are especially important. Currently, diagnosis is aided by the use of screening assays for fecal occult blood, sigmoidoscopy, colonoscopy and double contrast barium enemas. Treatment regimens are determined by the type and stage of the cancer, and include surgery, radiation therapy and/or chemotherapy. Recurrence following surgery (the most common form of therapy) is a major problem and is often the ultimate cause of death. In spite of considerable research into therapies for the disease, colon cancer remains difficult to diagnose and treat. Web site: http://www.delphion.com/details?pn=US06284241__ ·
Detection of inherited and somatic mutations of APC gene in colorectal cancer of humans Inventor(s): Vogelstein; Bert (Baltimore, MD), White; Raymond L. (Salt Lake City, UT), Thliveris; Andrew (Salt Lake City, UT), Albertsen; Hans (Salt Lake City, UT), Nakamura; Yusuke (Tokyo, JP), Anand; Rakesh (Cheshire, GB2), Carlson; Mary (Salt Lake City, UT), Groden; Joanna (Salt Lake City, UT), Hedge; Philip John (Cheshire, GB2), Joslyn; Geoff (Salt Lake City, UT), Kinzler; Kenneth (Baltimore, MD), Markham; Alexander (Cheshire, GB2) Assignee(s): The John Hopkins University (Baltimore, MD), Japanese Foundation for Cancer Research Cancer Institute (Tokyo, JP), University of Utah (Salt Lake City, UT), Zeneca Limited (Cheshire, GB2) Patent Number: 5,648,212 Date filed: August 12, 1994 Abstract: Methods are provided for assessing mutations of the APC gene in human tissues and body samples. APC mutations are found in familial adenomatous polyposis patients as well as in sporadic colorectal cancer patients. APC is expressed in most normal tissues. APC is a tumor suppressor. Excerpt(s): The invention relates to the area of cancer diagnostics and therapeutics. More particularly, the invention relates to detection of the germline and somatic alterations of wild-type APC genes. In addition, it relates to therapeutic intervention to restore-the function of APC (adenomatous Poliposis Coli) gene product.... In order to fully understand the pathogenesis of tumors, it will be necessary to identify the other suppressor genes that play a role in the tumorigenesis process. Prominent among these is the one(s) presumptively located at 5q21. Cytogenetic (Herrera et al., Am J. Med. Genet., Vol. 25, p. 473 (1986) and linkage (Leppert et al., Science, Vol. 238, p. 1411 (1987); Bodmer et al., Nature, Vol. 328, p. 614 (1987)) studies have shown that this chromosome
Patents 369
region harbors the gene responsible for familial adenomatous polyposis (FAP) and Gardner's Syndrome (GS). FAP is an autosomal-dominant, inherited disease in which affected individuals develop hundreds to thousands of adenomatous polyps, some of which progress to malignancy. GS is a variant of FAP in which desmoid tumors, osteomas and other soft tissue tumors occur together with multiple adenomas of the colon and rectum. A less severe form of polyposis has been identified in which only a few (2-40) polyps develop. This condition also is familial and is linked to the same chromosomal markers as FAP and GS (Leppert et al., New England Journal of Medicine, Vol. 322, pp. 904-908, 1990.) Additionally, this chromosomal region is often deleted from the adenomas (Vogelstein et al., N. Engl. J. Med., Vol. 319, p. 525 (1988)) and carcinomas (Vogelstein et al., N. Engl. J. Med., Vol. 319, p. 525 (1988); Solomon et al., Nature, Vol. 328, p. 616 (1987); Sasaki et al., Cancer Research, Vol. 49, p. 4402 (1989); Delattre et al., Lancet, Vol. 2, p. 353 (1989); and Ashton-Rickardt et al., Oncogene, Vol. 4, p. 1169 (1989)) of patients without FAP (sporadic tumors). Thus, a putative suppressor gene on chromosome 5q21 appears to play a role in the early stages of colorectal neoplasia in both sporadic and familial tumors.... Although the MCC gene has been identified on 5q21 as a candidate suppressor gene, it does not appear to be altered in FAP or GS patients. Thus there is a need in the art for investigations of this chromosomal region to identify genes and to determine if any of such genes are associated with FAP and/or GS and the process of tumorigenesis. Web site: http://www.delphion.com/details?pn=US05648212__ ·
Diagnosis and monitoring of colon cancer patients by measurement of NCA 50/90 in blood Inventor(s): Yeung; Kwok K. (Prospect, CT), Allard; William Jeffrey (Poughquag, NY) Assignee(s): Bayer Corporation (Tarrytown, NY) Patent Number: 6,309,846 Date filed: November 22, 1996 Abstract: A method for aiding in the diagnosis of, and monitoring the progression or course of, colon cancer in a patient by measuring the amount of NCA 50/90 in a blood sample, e.g., serum sample, obtained from the patient. Measurement in a single sample of an amount of NCA 50/90 significantly higher than the mean amount of NCA 50/90 in the normal population is an indication of colon cancer in a symptomatic patient. The course of colon cancer can also be monitored by performing a series of specific immunoassays over time to determine changes in the level of NCA 50/90 in blood samples. Increases in blood NCA 50/90 levels over time are indicative of a deteriorating condition whereas decreasing levels of blood NCA 50/90 over time indicate an improving condition. Excerpt(s): The present invention relates to the diagnosis of, and monitoring the progression, course, or stage of, disease in colon cancer patients. More particularly, the invention relates to such diagnostic and monitoring methods based on measurement of cancer marker blood levels.... A family of antigenic proteins have been identified which are genetically and immunologically related to CEA (Thompson, J. and W. Zimmerman (1988) Tumor Biol. 9, 63-83; and Barnett, T. and W. Zimmerman (1990) Tumor Biol. 11, 59-63). Among these are the nonspecific cross-reacting antigens (NCAs), the transmembrane antigens designated biliary glycoprotein (BGP, and sometimes referred to as TM-CEAs), and the family of pregnancy-specific.beta.-glycoproteins (PSGs) (for a description of the accepted nomenclature of these genes and their protein products,
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reference can be made to: Barnett, T. and W. Zimmerman (1990) Tumor Biol. 11, 59-63). Molecular cloning of the CEA gene family has enabled the identification of 22 members, of which 20 are probably expressed (Frangsmyr, L. et al. (1992) Tumor Biol. 13, 98-99; and Hammerstrom, S. et al Tumor Biol. 13, 57). The results of molecular genetic analysis have given a better understanding of the complex group of glycoproteins in the CEA gene family.... Early studies also identified a cross-reacting antigen from adult stools and from meconium which, for historical reasons, was termed NCA-2 (Burtin, P., Chavenel, G. and H. Hirsch-Marie (1973) J. Immunol. 111, 1926-1928). Indeed, a recent report suggests that variability in CEA results obtained with different commercial kits may be due to interference with NCA-2 (O. P. Bormer (1991) Clin. Chem. 37, 1736-1739). The designation of this antigen as NCA is, however, a misnomer. It has been identified as a proteolytic fragment of CEA, since the first 30 amino acids of the meconium-derived NCA-2 are identical in sequence with CEA (Siepen, D. et al (1987) Biochem. Biophys. Res. Commun. 174, 212-218). In contrast, cDNAs for NCA 50/90 have been described and code for distinct and different amino acid sequences in this region. Web site: http://www.delphion.com/details?pn=US06309846__ ·
Fructan containing composition for the prevention and treatment of colon cancer and method for the prevention and treatment of same Inventor(s): Frippiat; Anne (Sterrebeek, BE), Van Loo; Jan (Leuven, BE) Assignee(s): Tiense Suikerraffinaderij N.V. (BE) Patent Number: 6,500,805 Date filed: November 19, 1999 Abstract: The use is provided of a fructran with an average degree of polymerisation of at least 15 for the manufacture of a composition for the prevention and/or treatment of colon cancer in non-bovine mammals, particularly in human beings.Also provided is a method of prevention and treatment of colon cancer in a non-bovine mammal, particularly in a human being, comprising administering to said mammal a composition comprising an effective dose of a fructan with an average degree of polymerisation of at least 15.The said composition can be a medicament as well as a functional food. In a preferrred embodiment the fructan is inulin, more preferably inulin with an average degree of polymerisation of at least 20. Excerpt(s): The present invention relates to the use of certain fructans, preferably certain inulins, for the manufacture of a composition for the prevention and/or treatment of colon cancer in non-bovine mammals.... The present invention also relates to the use of compositions comprising certain fructans, preferably certain inulins, for the prevention and/or treatment of colon cancer in non-bovine mammals, and to a method of prevention and/or treatment of colon cancer in non-bovine mammals.... Cancer in mammals is a disease which is already known from Ancient Times. Nowadays cancer, particularly lung, breast and colon cancer, has become one of the major causes of death of non-bovine mammals, in particular of humans, in the industrialised world. Web site: http://www.delphion.com/details?pn=US06500805__
Patents 371
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Hybridoma CT43 producing a monoclonal antibody to a novel mucin epitope which correlates with the presence of colorectal cancer Inventor(s): Brown; Joseph P. (Seattle, WA) Assignee(s): Genetic Systems Corporation (Redmond, WA) Patent Number: 5,459,043 Date filed: December 3, 1992 Abstract: The present invention relates to a novel monoclonal antibody reactive with human colorectal mucin antigen. More particularly, the antibody of the invention is a murine monoclonal antibody, CT43, reactive with a novel antigenic determinant on much antigen highly correlated with human colorectal cancer. The antigenic determinant found by the CT43 has been characterized as neuraminidase and proteinase K resistant, periodate sensitive and unreactive with the glycoconjugates of Table 2. Methods are provided for the detection and quantitation of the CT43 antigenic determinant and its correlation with colorectal cancer. CT43, and CT66 specific for the sialylated Lewis a and Lewis a antigen have been deposited with the American Type Culture Collection, as accession numbers ATCC HB 10217 and ATCC HB 10218, deposited Sep. 6, 1989. Excerpt(s): This invention relates to the hybridoma cell line CT43 which produces a monoclonal antibody reactive with mucins, particularly a novel epitope on mucin molecules associated with colorectal cancer malignancies. Monoclonal antibody CT43 and other antibodies specific for the epitope recognized by CT43 are useful in the detection and treatment of human cancers, particularly colorectal cancer.... The diagnosis of colorectal cancer is currently based upon clinical findings, detection of blood in fecal samples, and a correlation with high level of certain carcinoma- associated mucin antigens in tissue, blood, or serum samples detected by the binding of certain monoclonal antibodies. Examples of monoclonal antibodies which have been reported to recognize antigens associated with gastrointestinal or colorectal cancer include CA 19-9 (Magnani, J. L. et al. supra), CCK061 (European Patent Application, EP200464) and a monoclonal antibody specific for carcinoembryonic antigen (1116NS-3d), U.S. Pat. No. 4,349,528). In vitro diagnostic methods for detecting the presence of cancer cells or other cancer cells producing small intestine mucin antigens and/or large intestine mucin antigen and monoclonal antibodies useful therein are disclosed by Linnane (PCT Publication WO 86/00414). Many other malignant conditions are also detected, in addition to colorectal carcinoma (e.g., stomach, gall bladder, malignant lymphoma and acute lymphocytic leukemia). Diagnostic tests based on each of the antigens recognized by the above antibodies fail to have a high correlation with colorectal carcinoma, particularly in its early stages, resulting in high numbers of false positive results. The only truly reliable method to date is biopsy of potentially malignant growths. Monoclonal antibodies such as CEA or CA 19- 9 are used in conjunction with other diagnostic methods or in post-therapy survey for cancer recurrance.... The present invention provides a monoclonal antibody that is highly reactive with mucin epitopes associated with human colorectal cancer. More specifically, the novel antibody of the invention, designated CT43, is a murine monoclonal antibody that binds a novel epitope on the membrane of colorectal carcinoma cells and also on mucin molecules found in human sera of patients suffering from colorectal cancer. The novel mucin epitope is characterized as being neuraminidase and proteinase K resistant, periodate sensitive and unreactive with many known, naturally occuring glycoconjugates. Web site: http://www.delphion.com/details?pn=US05459043__
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Imaging of colorectal cancer using ST receptor binding compounds Inventor(s): Waldman; Scott A. (Ardmore, PA) Assignee(s): Thomas Jefferson University (Philadelphia, PA) Patent Number: 6,268,159 Date filed: August 21, 1998 Abstract: Conjugated compounds which comprises an ST receptor binding moiety and a radiostable active moiety are disclosed. Pharmaceutical compositions comprising a pharmaceutically acceptable carrier or diluent, and a conjugated compound which comprises an ST receptor binding moiety and a radiostable active moiety or an ST receptor binding moiety and a radioactive active moiety are disclosed. Methods of treating an individual suspected of suffering from metastasized colorectal cancer comprising the steps of administering to said individual a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent, and a therapeutically effective amount of a conjugated compound which comprises an ST receptor binding moiety and a radiostable active moiety or an ST receptor binding moiety and a radiostable active moiety are disclosed. Methods of radioimaging metastasized colorectal cancer cells comprising the steps of first administering to an individual suspected of having metastasized colorectal cancer cells, a pharmaceutical composition that comprises a pharmaceutically acceptable carrier or diluent, and conjugated compound that comprises an ST receptor binding moiety and a radioactive active moiety wherein the conjugated compound is present in an amount effective for diagnostic use in humans suffering from colorectal cancer and then detecting the localization and accumulation of radioactivity in the individual's body are disclosed. Excerpt(s): The present invention relates to compounds which comprise a receptor ligand moiety conjugated to an active agent. More particularly, the present invention relates to compounds which comprise a moiety that binds to the ST receptor conjugated to a therapeutic or imaging moiety.... Colorectal cancer is the third most common neoplasm worldwide and the second most common in the United States, representing about 15% of the newly diagnosed cases of cancer in the United States. The large intestine or large bowel is the third leading site for the development of new cancer and is diagnosed in about 150,000 patients each year. Colorectal cancer is the second leading cause of cancer-related deaths and is responsible for about 12% of cancer deaths in the United States. The mortality rate of newly diagnosed large bowel cancer approaches 50% and there has been little improvement over the past 40 years. Most of this mortality reflects local, regional and distant metastases. About thirty percent of patients with colorectal cancer have unresectable disease at presentation and about 40% develop metastases during the course of their disease. Distant metastatic disease is seen in liver (about 12%), lung (about 3%), bone (about 0.9%), brain (about 0.7%), nodes (about 4%), and peritoneum (about 2%) at the time of initial diagnosis. In 1987, the large bowel cancers found regionally or at distant sites at the time of diagnosis were about 26% and about 18%, respectively.... Surgery is the mainstay of treatment for colorectal cancer but recurrence is frequent. Colorectal cancer has proven resistant to chemotherapy, although limited success has been achieved using a combination of 5-fluorouracil and levamisole. Surgery has had the largest impact on survival and, in some patients with limited disease, achieves a cure. However, surgery removes bulk tumor, leaving behind microscopic residual disease which ultimately results in recrudescence. Overall recurrence rates for colonic tumors are about 33% and for rectal cancer about 42%. Of
Patents 373
these recurrences, about 9% are local, about 13% are systemic metastatic disease, and the remaining 88% are a combination of local and systemic disease. Fifty percent of patients with recurrent colorectal cancer have hepatic metastases. Web site: http://www.delphion.com/details?pn=US06268159__ ·
Isolated nucleic acid molecules associated with colon cancer and methods for diagnosing and treating colon cancer Inventor(s): Old; Lloyd J. (New York, NY), Stockert; Elisabeth (New York, NY), Chen; Yao-Tseng (New York, NY), Scanlan; Matthew J. (New York, NY) Assignee(s): Ludwig Institute for Cancer Research (New York, NY) Patent Number: 6,043,084 Date filed: October 10, 1997 Abstract: Various molecules associated with disorders such as colon cancer are disclosed. The invention also discloses diagnostic and therapeutic methods based upon these molecules. Excerpt(s): This invention relates to the isolation of genes associated with colon cancer, methods of diagnosing colon cancer using these, as well as other genes which are known, as well as therapeutic approaches to treating such conditions.... It is fairly well established that many pathological conditions, such as infections, cancer, autoimmune disorders, etc., are characterized by the inappropriate expression of certain molecules. These molecules thus serve as "markers" for a particular pathological or abnormal condition. Apart from their use as diagnostic "targets", i.e., materials to be identified to diagnose these abnormal conditions, the molecules serve as reagents which can be used to generate diagnostic and/or therapeutic agents. A by no means limiting example of this is the use of cancer markers to produce antibodies specific to a particular marker. Yet another non-limiting example is the use of a peptide which complexes with an MHC molecule, to generate cytolytic T cells against abnormal cells.... Preparation of such materials, of course, presupposes a source of the reagents used to generate these. Purification from cells is one laborious, far from sure method of doing so. Another preferred method is the isolation of nucleic acid molecules which encode a particular marker, followed by the use of the isolated encoding molecule to express the desired molecule. Web site: http://www.delphion.com/details?pn=US06043084__
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Medicinal compositions for treating colorectal cancer Inventor(s): Tomizawa; Naoko (Ibaraki, JP), Tanida; Norifumi (Ibaraki, JP), Goto; Takeshi (Ibaraki, JP) Assignee(s): Hisamitsu Pharmaceutical Co., Inc. (Saga, JP) Patent Number: 6,620,834 Date filed: April 15, 2002 Abstract: Medicinal compositions for colorectal cancer to be administered to the large intestine by taking advantage of preparations disintegrating in the large intestine, characterized by containing a cyclooxygenase inhibitor and an HMG-CoA reductase
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inhibitor. These compositions are appropriate for inhibiting the postoperative liver metastasis and recurrence of colorectal cancer. Excerpt(s): The invention relates to a pharmaceutical composition to be administered to the large intestine for treating a colorectal cancer.... In cancer therapy the surgical treatment is the mainstream at present. However, in order to improve the performance of the surgical treatment further, an ancillary use of chemotherapy is indispensable. Since cases of cancer metastasis to the liver or lung due to a hemokinetic metastasis from, in particular, the colorectal cancer is frequently observed, a postoperative ancillary chemotherapy has become essential. For the chemotherapy aiming to inhibit the postoperative metastasis and recurrence of cancer, usually an oral anticancer agent represented by 5-fluorouracil is mainly used. In case of using such an anticancer agent expecting the metastasis inhibition or recurrence prevention, a medicine-taking period for one year or more is necessary, though the present situation is that the medication is compelled to be abandoned owing to the development of a strong digestive tract disorder or a systemic side effect such as a severe myelosuppression. Therefore, naturally there is limitation for achieving the above object only by the chemotherapy mainly using an anticancer agent.... Further, in case of making the chemotherapy aim to prevent especially the postoperative liver metastasis of colorectal cancer, it is important to carry out a drug delivery from the mesenteric vein to the portal in a metastasis route of cancer cells and to maintain a drug concentration in the portal blood. Web site: http://www.delphion.com/details?pn=US06620834__ ·
Metastatic breast and colon cancer regulated genes Inventor(s): Giese; Klaus (Berlin, DE) Assignee(s): Chiron Corporation (Emeryville, CA) Patent Number: 6,468,790 Date filed: November 13, 2000 Abstract: Gene sequences as shown in SEQ ID NOS:1-85 have been found to be significantly associated with metastatic potential of cancer cells, especially breast and colon cancer cells. Methods are provided for determining the risk of metastasis of a tumor, which involve determining whether a tissue sample from a tumor expresses a polypeptide encoded by a gene as shown in SEQ ID NOS:1-85, or a substantial portion thereof. Excerpt(s): This invention relates to methods for predicting the behavior of tumors. More particularly, the invention relates to methods in which a tumor sample is examined for expression of a specified gene sequence thereby to indicate propensity for metastatic spread.... It is an object of the present invention to provide markers for distinguishing between tumors which will or have metastasized and those which are less likely to metastasize. These and other objects of the invention are provided by one or more of the embodiments described below.... One embodiment of the invention provides an isolated and purified human protein having an amino acid sequence which is at least 85% identical to an amino acid sequence encoded by a nucleotide sequence selected from the group consisting of SEQ ID NOS:1-63 or the complement thereof. Web site: http://www.delphion.com/details?pn=US06468790__
Patents 375
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Method for colorectal cancer prognosis and treatment selection Inventor(s): Ross; Jeffrey S. (New Lebanon, NY) Assignee(s): Albany Medical College (Albany, NY) Patent Number: 6,322,986 Date filed: January 18, 2000 Abstract: A method predicting the outcome, and prognosis and indicating treatment for patients afflicted with colorectal cancer by determining whether the number of copies of HER-2/neu gene in cancer cells from the patient exceeds four by in-situ hybridization. Patients having cells with five or more copies of the HER-2/neu gene are to be treated more aggressively or in combination with an anti-HER-2/neu antibody. Excerpt(s): The present invention relates to predicting the outcome and selecting preferred treatments for colorectal cancer by DNA analysis.... Colorectal cancer is a common cancer in the developed world and is a major cause of cancer death. The disease is diagnosed in about 129,400 people and is responsible for nearly 56,600 deaths per year in the United States alone. Traditional therapies for colorectal cancer include surgery, radiation therapy, and chemotherapy, with 5-fluorouracil, levamisole, leucovorin or semustine (methyl CCNU) being the preferred chemotherapeutic agents for colorectal adenocarcinoma.... After surgery or other treatment the ability to predict recurrence and to treat the patient appropriately becomes problematic. Post-surgical treatments have numerous undesired side effects which one wishes to avoid if possible. Conversely, failure to adequately treat any residual tumor cells may result in recurrence of the cancer. Pathological stage, clinical stage, patient age, various protein markers and cell proliferation index are each indicative of the aggressiveness of the cancer and prognostic of eventual outcome. Examples of such indicators may be found in Cohn et al, Cancer 79:233-44 (1997), Finkelstein et al, Cancer 71(12):3827-3838 (1993), Harrison et al, Human Pathology 26(1):31-38 (1995), Furuta et al, Clinical Cancer Research 4:21-29 (1998), Tanigawa et al, Cancer Research 57:1043-1046 (1997), Ropponen et al, Cancer Research 58:342-347 (1998), Wielenga et al, Cancer Research 53:4754-4756 (1993), Halter et al, Modern Pathology 5(2):131-134 (1992), Tanabe et al, Lancet, 341:725-726 (1993), Lanza et al, Anatomic Pathology 105(5):604-612 (1996), Graham et al, Modern Pathology 3(3):332-335 (1990), Engel et al, The American Journal of Surgical Pathology 20(10):12601265 (1996), Suzuki et al, Gastroenterology 109:1098-1104 (1995), Morrin et al, Gut 35:1627-1631 (1994) and Nakamori et al, Gastroenterology 106:353-361 (1994). Web site: http://www.delphion.com/details?pn=US06322986__
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Method of detecting colon cancer Inventor(s): Nehlsen-Cannarella; Sandra (652 E. Mariposa Dr., Redlands, CA 92373), Fagoaga; Omar (1834 Northwestern Cir., Colton, CA 92324), McCracken; John D. (646 Valleyview Dr., Redlands, CA 92373), Pant; Keshab D. (341 Aurora Dr., Perris, CA 92571), Kelln; Wayne (25232 Lawton Ave., Loma Linda, CA 92354) Assignee(s): none reported Patent Number: 6,531,319 Date filed: May 10, 2000 Abstract: An immunological assay and kit for colon cancer screening is disclosed. Fecal glycoproteins are extracted from individual samples such that immunogenicity is
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maintained. The purified fecal glycoproteins are reacted with antibodies to Colon and Ovarian Tumor Antigen (COTA). The mucin antigen COTA is specifically present in colorectal cancer tissue and not in normal colons. The amount of COTA in the fecal sample is determined and used to indicate the presence of colon cancer. Excerpt(s): The present invention is directed to a method for detecting colon cancer utilizing an antibody specific for a glycoprotein found in colon cancer cells.... Colorectal cancer is among the leading causes of cancer-related morbidity and mortality in industrialized nations. The pathogenesis is related to hereditary influences, modified by the quantity and quality of dietary fat. In 1995, the American Cancer society estimated that 135,000 new cases of colon cancer were diagnosed; 71% were in the colon and 30% were in the rectum. Patients diagnosed at an early stage, prior to lymph-node spread, are potentially cured with surgery. At present, only 41% of patients are diagnosed at an early stage. The remaining cases frequently undergo peri-operative radiation and/or chemotherapy to attempt to control the metastatic spread of disease. Ultimately, 50% of patients thought to have undergone curative resections eventually develop recurrent disease. Unfortunately, 55,000 Americans die each year due to recurrent or metastatic colon or rectal cancer. The key to enhanced survival is early diagnosis. Colon and rectal cancers are often silent and slowly progressive. Most patients exhibit symptoms such as rectal bleeding, pain, abdominal distension or weight loss only after the disease is advanced and not surgically curable.... Over the past 25 years, early colorectal cancer detection has been based on the fecal occult blood test (FOBT) performed annually on asymptomatic individuals. Current recommendations adapted by several healthcare organizations, including the American Cancer Society, call for fecal occult blood testing beginning at age 50, repeated annually until such time as the patient would no longer benefit from screening. A positive FOBT leads to colonoscopic examination of the bowel; an expensive and invasive procedure, with a serious complication rate of one per 5,000 examinations. Only 12% of patients with heme positive stool are diagnosed with cancer or large polyps at the time of colonoscopy. Most studies show that FOBT screening does not improve cancer-related mortality or overall survival. Compliance with occult blood testing has been poor; less than 20percent of the population is offered or completes FOBT as recommended. If FOBT is properly done, the patient collects a fecal sample from three consecutive bowel movements. Samples are obtained while the patient adheres to dietary guidelines and avoids medications known to induce occult gastrointestinal bleeding. In reality, physicians frequently fail to instruct patients properly, patients frequently fail to adhere to protocol, and some patients find the task of collecting fecal samples difficult or unpleasant, hence compliance with annual occult blood testing is poor. Compounding the problem of compliance, the sensitivity and specificity of FOBT to detect colon cancer is poor. In eight prospective studies where hemoccult testing was followed by colonoscopy, only 41 of 159 cancers diagnosed were detected by FOBT, yielding a screening sensitivity of 26%. FOBT sensitivity for precancerous polyps was also poor. Poor test specificity leads to unnecessary colonoscopy, adding considerable expense to colon cancer screening. In the University of Minnesota trial, a large prospective hemoccult screening study, test specificity was 90%, and positive predictive value was 2%. Only one colon cancer was found in every 50 testtriggered colonoscopies performed. Web site: http://www.delphion.com/details?pn=US06531319__
Patents 377
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Method of diagnosing and monitoring colorectal cancer Inventor(s): Holmes; Stephen D. (Great Chishill, GB2), Kirkpatrick; Robert B. (King of Prussia, PA), Robbins; David (King of Prussia, PA) Assignee(s): SmithKline Beechum Corporation (King of Prussia, PA) Patent Number: 5,726,061 Date filed: October 8, 1996 Abstract: Methods of screening for colorectal cancer by measuring levels of HC gp-39 are provided. Methods of monitoring patients with colorectal cancer are also provided. In addition, kits for detection of HC gp-39 useful in screening for and monitoring of colorectal cancer in a patient are provided. Excerpt(s): Colorectal cancer is a leading cause of death in the western hemisphere. It is currently the second most common neoplasm, as well as the second leading cause of death due to cancer, in the United States. Risk factors for colorectal cancer include familial and genetic factors, and may include low levels of physical activity, alcohol consumption, high dietary intake of fat and meat and low intake of fiber and vegetables. Age also appears to be a significant risk factor as less than 2% of the cases occur in people under 40 years of age. The risk of colorectal cancer in a patient 50 years of age is 18 to 20 times that in a patient 30 years of age and the risk doubles about every 7 years thereafter.... The prognosis of colorectal cancer is directly related to the stage at which the cancer is detected. When detected early, either as an adenoma or wherein the tumor is confined to the bowel wall, the cancer can be treated effectively with a greater than 90%, five-year survival rate. However, in later stages, colorectal cancer spreads to local and regional lymph nodes, with the most common distant metastatic sites being the liver and the lung, thus making methods of treatment much less effective.... The World Health Organization in Geneva Switzerland has outlined certain requirements for determining when screening for a specific disease might be beneficial. First, the disease is a major cause of morbidity and/or mortality. Second, the treatment must be effective and risks of screening low. Third, the test must be both efficacious and cost-effective. Fourth, the test must have high sensitivity and specificity. Finally, the test must be acceptable to the general population and to the physicians who implement the screening. Colorectal cancer clearly meets these requirements. In fact, there are several tests currently being recommended by the American Cancer Society for colorectal screening, i.e., flexible sigmoidoscopy and fecal occult blood tests. Digital rectal examination has also been suggested. Wayne et al. Arch. Fam. Med., 1995, 4, 357-366. Web site: http://www.delphion.com/details?pn=US05726061__
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Method of preparing activated killer monocytes for treating colorectal cancer Inventor(s): Stevenson; Henry C. (Kensington, MD) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 5,093,115 Date filed: June 20, 1988 Abstract: The present invention discloses a method of preparing activated killer monocytes for treating colorectal cancer. Activated killer monocytes are prepared in serum free medium in polypropylene containers.
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Excerpt(s): The present invention is related generally to cancer therapy. More particularly, the present invention is related to monitoring in cancer patients the tumoricidal activity of purified human monocytes cultured in suspension in a serumfree medium.... Mononuclear phagocytes (monocytes) in their various forms have been shown to participate in many critical phases of the mammalian immune response. Monocytes and macrophages are known to be essential for the initiation of immune responses by virtue of their ability to process antigen (Rosenthal, New Engl. J. Med. 303, 1153. 1980), and for their ability to secrete soluble factors such as interleukin 1 (IL-1), colony stimulating factor (CSF), interferon (IFN) and prostaglandin E (PGE) which allow them to function as immunoregulators for a number of immune responses (Epstein, Biology of Lymphokines; Academic Press, NY, pp. 123-152. 1979; Stevenson, The Reticuloendothelial System. A Comprehensive Treatise, Vol. VI: Plenum Press, NY, pp. 79-91. 19882). In addition, monocytes are known to play critical role as final effector cells in humoral immunity by virtue of the fact that these cells secrete complement components (Nathan, et al, New England J. Med. 303, 623. 1980) and are capable of mediating cytotoxic functions. In addition to antibody-dependent cellular cytotoxicity (ADCC) (Poplack, et al, Blood 48, 890. 1976), activated killer monocytes (AKM) are known to be potent killers of tumor cells (Stevenson, et al, Artificial Organs 112, 128. 1988).... Assessment of the in vitro function of human monocytes and AKM has been hampered by a number of technical and theoretical problems. First, monocytes constitute a very low proportion of the cells in human peripheral blood (generally less than 5%); thus, obtaining large numbers of them has been quite difficult. In addition, very few techniques have emerged which allow for the large-scale isolation of purified populations of human monocytes by negative selection; instead, generally small numbers of rather impure monocytes are isolated on gradients such as Percoll (Hester, et al., 1981) or cells of higher purity are obtained by adhering them onto plastic or glass labware by positive selection (Werb, J. Exp. Med. 147, 1695. 1978). Web site: http://www.delphion.com/details?pn=US05093115__ ·
Method of preventing colon cancer with vitamin D.sub.3 analogues Inventor(s): Bissonnette; Bruce Marc (Chicago, IL), Brasitus; Thomas A. (Olympia Fields, IL), Sitrin; Michael D. (Flossmoor, IL) Assignee(s): Arch Development Corporation (Chicago, IL) Patent Number: 6,040,300 Date filed: April 7, 1995 Abstract: A method for preventing the initiation of colon cancer is disclosed. Vitamin D.sub.3 analogues prevented the development of adenomas and adenocarcinomas when administered to rats prior to, and subsequent to, chemically induced tumorigenesis. Excerpt(s): The present invention relates generally to the field of cancer prevention. In particular, the invention relates to a method of preventing colon cancer by vitamin D.sub.3 analogues. In one example, administration of 1.alpha., 25-Dihydroxy-16-ene-23yne-26, 27-hexafluorocholecalciferol reduced the incidence of colon cancer in rats.... Colon cancer is a leading cause of death among patients with internal malignancies in the United States and, unfortunately, at the time of initial diagnosis is incurable in approximately one-half of the patients found to harbor this malignancy (Zarling and Rhodes, Int. Med. Specialist 3:72-86, 1982). Moreover, despite advances in the fields of surgery, radiotherapy and chemotherapy, the cure rate for this disease has not improved significantly (Zarling and Rhodes, 1982). Based on these considerations, the search for
Patents 379
strategies to prevent the development of cancers in this organ has markedly intensified during the past decade.... Although the cause of large bowel cancer is not known, most epidemiologists associate it with diet, and, in particular, the low-fiber, high-protein, high-fat content that characterizes the diet of most Americans and people in other urban, industrialized societies. Many observers believe that colon cancer is the first major cancer type for which available evidence is sufficient to recommend dietary changes in the general public (Willett, Nature 338:384, 1989; Greenwald, Cancer 70 (Suppl.): 1206, 1992). In this regard, the possibility of using dietary supplements as a strategy to prevent colon cancer has recently been recognized (Mukhtar and Athar, Clev. Clin. J. Med. 55:507-508, 1988). Web site: http://www.delphion.com/details?pn=US06040300__ ·
Method of screening for colorectal cancer Inventor(s): Mashiba; Shinichi (Kyoto-fu, JP), Uchida; Kazuo (Hyogo-ken, JP) Assignee(s): Ikagaku Co., Ltd. (Kyoto, JP) Patent Number: 5,552,292 Date filed: November 10, 1994 Abstract: The invention provides a new method for screening for colorectal cancer by measurement of the level of lactoferrin or myeloperoxidase in feces. Particularly, a screening test method for colorectal cancer by measurement of the level of lactoferrin or myeloperoxidase in feces by immunoassay and by measurement of the level of wholesized lactoferrin by immunoassay utilizing monoclonal antibody. Excerpt(s): In various kinds of gastrointestinal tract diseases such as inflammatory gastrointestinal disorders and gastrointestinal cancer, intestinal chronic bleeding is observed in inflammation neoplasia at the mucous membrane, or protein leaking in gastrointestinal tract is observed due to permeability disorder of capillary blood vessel or pressure raise of lymphoduct.... In order to diagnose the gastrointestinal tract diseases, the fecal occult blood test method has most been used for screening of gastrointestinal tract diseases with bleeding, especially for mass screening of colorectal cancer.... Among the fecal occult blood test, the guaiac method is the most widely used and the method utilizes the peroxidase activity of the heme in hemoglobin, hence not only human hemoglobin in feces, but also hemoglobin from animal and fish meat or special vegetable is detected by this method. Since human hemoglobin is not detected specifically by the Guaiac method, subjects are required to follow a special diet in order to prevent the occurrence of false positive results. Moreover, it has been difficult to increase the sensitivity of this method. Web site: http://www.delphion.com/details?pn=US05552292__
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Method of treating or inhibiting colonic polyps and colorectal cancer Inventor(s): Discafani-Marro; Carolyn M. (Cortlandt Manor, NY), Frost; Philip (Morris Township, NJ) Assignee(s): American Cyanamid Company (Madison, NJ) Patent Number: 6,432,979 Date filed: August 9, 2000
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Abstract: This invention provides a method of treating or inhibiting colonic polyps or treating or inhibiting colorectal cancer in a mammal in need thereof which comprises administering to said mammal an NSAID and an EFGR kinase inhibitor. Excerpt(s): This invention relates to the use of a combination of an NSAID and a epidermal growth factor receptor (EGFR) kinase inhibitor in the treatment and inhibition of colonic polyps and colorectal cancer.... Colonic Polyps occur in both a familial pattern (familial adenomatous polyps; FAP) and sporadically. FAP afflicts approximately 25,000 patients in the US; while it is estimated that sporadic adenomatous polyps (SAP) occur in approximately 2 million people per year in the US alone. All these patients are at risk for developing adenocarcinoma of the colon. In the case of FAP, that risk is virtually 100% and these patients usually undergo a colectomy at an early age. Patients with sporadic polyps are treated with polypectomy and require periodic colonoscopic examination because of their inherent risk of developing recurrent polyps. In fact, parents and siblings of these patients are also at increased risk for developing colorectal cancer.... The genetic basis for FAP has been linked to the presence of mutations in the APC gene. Similar APC mutations have been found in patients with sporadic polyps. Biochemically, the APC mutation occurs in conjunction with the increased expression of cyclooxygenase enzymes, particularly COX-2. These enzymes are essential for the production of prostenoids, (prostaglandin's; (PG's)) that mediate a number of functions in the bowel including motility, vascular tone, angiogenesis and mucosal protection. PG's are also purported to discourage apoptosis and this is proposed as an explanation for polyp formation. Web site: http://www.delphion.com/details?pn=US06432979__ ·
Methods of diagnosing colorectal cancer, compositions, and methods of screening for colorectal cancer modulators Inventor(s): Gish; Kurt C. (San Francisco, CA), Mack; David (Menlo Park, CA), Wilson; Keith E. (Redwood City, CA) Assignee(s): Eos Biotechnology, Inc. (South San Francisco, CA) Patent Number: 6,455,668 Date filed: September 6, 2000 Abstract: Described herein are methods that can be used for diagnosis and prognosis of colorectal cancer. Also described herein are methods that can be used to screen candidate bioactive agents for the ability to modulate colorectal cancer. Additionally, methods and molecular targets (genes and their products) for therapeutic intervention in colorectal cancer are described. Excerpt(s): The invention relates to the identification of expression profiles and the nucleic acids involved in colorectal cancer, and to the use of such expression profiles and nucleic acids in diagnosis and prognosis of colorectal cancer. The invention further relates to methods for identifying and using candidate agents and/or targets which modulate colorectal cancer.... Colorectal cancer is a significant cancer in Western populations. It develops as the result of a pathologic transformation of normal colon epithelium to an invasive cancer. There have been a number of recently characterized genetic alterations that have been implicated in colorectal cancer, including mutations in two classes of genes, tumor-suppressor genes and proto-oncogenes, with recent work suggesting that mutations in DNA repair genes may also be involved in tumorigenesis. For example, inactivating mutations of both alleles of the adenomatous polyposis coli
Patents 381
(APC) gene, a tumor suppressor gene, appears to be one of the earliest events in colorectal cancer, and may even be the initiating event. Other genes implicated in colorectal cancer include the MCC gene, the p53 gene, the DCC (deleted in colorectal carcinoma) gene and other chromosome 18q genes, and genes in the TGF-.beta. signalling pathway. For a review, see Molecular Biology of Colorectal Cancer, pp238299, in Curr. Probl. Cancer, September/October 1997.... Imaging of colorectal cancer for diagnosis has been problematic and limited. In addition, dissemination of tumor cells (metastases) to locoregional lymph nodes is an important prognostic factor; five year survival rates drop from 80 percent in patients with no lymph node metastases to 45 to 50 percent in those patients who do have lymph node metastases. A recent report showed that micrometastases can be detected from lymph nodes using reverse transcriptase-PCR methods based on the presence of mRNA for carcinoembryonic antigen, which has previously been shown to be present in the vast majority of colorectal cancers but not in normal tissues. Liefers et al., New England J. of Med. 339(4):223 (1998). Web site: http://www.delphion.com/details?pn=US06455668__ ·
Methods of treating colon cancer utilizing tumor-specific antibodies Inventor(s): Gure; Ali Osmay (New York, NY), Barendswaard; Elsje (New York, NY), Old; Lloyd J. (New York, NY), Welt; Sydney (New York, NY), Montalto; Nicholas J. (New York, NY) Assignee(s): Ludwig Institute For Cancer Research (New York, NY) Patent Number: 5,958,412 Date filed: June 4, 1997 Abstract: This invention relates to methods of reducing the effects of colon cancer tumors. Various agents are conjugated to monoclonal antibodies which are specific for colon cancer cells. The conjugates are administered to patients having colon cancer such that the effects of the cancer are reduced. Excerpt(s): This invention relates to a method of reducing the effects of colon cancer tumors, utilizing at least one monoclonal antibody. Specifically, at least one monoclonal antibody is utilized in conjunction with an anti-tumor drug, a peptide which inhibits DNA tumor activity or a radioisotope in the treatment of colorectal carcinoma. This invention further relates to a method of delivering genetic material to DNA of tumor cells and to a method of delivering anti-cancer agents to nuclei of colon tumor cells, as well as to monoclonal antibodies which are specific for A33 antigen; an antigen found on colon cancer cells.... Colorectal carcinoma is a malignant neoplastic disease. There is a high incidence of colorectal carcinoma in the Western world, particularly in the United States. Tumors of this type often metastasize through lymphatic and vascular channels. Many patients with colorectal carcinoma eventually die from this disease. In fact, it is estimated that 62,000 persons in the United States alone die of colorectal carcinoma annually.... To date, systemic therapies and chemotherapies have been developed for the treatment of colorectal cancer. However, no therapies have exhibited sufficient antitumor activity to prolong the survival of colorectal carcinoma patients with metastatic disease with any degree of reliability. As a result, a need still exists to develop methods for the successful treatment of colorectal carcinoma. Web site: http://www.delphion.com/details?pn=US05958412__
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·
Methods of treating metastatic colorectal cancer with ST receptor binding compounds Inventor(s): Waldman; Scott A. (Ardmore, PA) Assignee(s): Thomas Jefferson University (Philadelphia, PA) Patent Number: 5,879,656 Date filed: January 5, 1996 Abstract: Conjugated compounds which comprises an ST receptor binding moiety and a radiostable active moiety are disclosed. Pharmaceutical compositions comprising a pharmaceutically acceptable carrier or diluent, and a conjugated compound which comprises an ST receptor binding moiety and a radiostable active moiety or an ST receptor binding moiety and a radioactive active moiety are disclosed. Methods of treating an individual suspected of suffering from metastasized colorectal cancer comprising the steps of administering to said individual a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent, and a therapeutically effective amount of a conjugated compound which comprises an ST receptor binding moiety and a radiostable active moiety or an ST receptor binding moiety and a radiostable active moiety are disclosed. Methods of radioimaging metastasized colorectal cancer cells comprising the steps of first administering to an individual suspected of having metastasized colorectal cancer cells, a pharmaceutical composition that comprises a pharmaceutically acceptable carrier or diluent, and conjugated compound that comprises an ST receptor binding moiety and a radioactive active moiety wherein the conjugated compound is present in an amount effective for diagnostic use in humans suffering from colorectal cancer and then detecting the localization and accumulation of radioactivity in the individual's body are disclosed. Excerpt(s): The present invention relates to compounds which comprise a receptor ligand moiety conjugated to an active agent. More particularly, the present invention relates to compounds which comprise a moiety that binds to the ST receptor conjugated to a therapeutic or imaging moiety.... Colorectal cancer is the third most common neoplasm worldwide and the second most common in the United States, representing about 15% of the newly diagnosed cases of cancer in the United States. The large intestine or large bowel is the third leading site for the development of new cancer and is diagnosed in about 150,000 patients each year. Colorectal cancer is the second leading cause of cancer-related deaths and is responsible for about 12% of cancer deaths in the United States. The mortality rate of newly diagnosed large bowel cancer approaches 50% and there has been little improvement over the past 40 years. Most of this mortality reflects local, regional and distant metastases. About thirty percent of patients with colorectal cancer have unresectable disease at presentation and about 40% develop metastases during the course of their disease. Distant metastatic disease is seen in liver (about 12%), lung (about 3%), bone (about 0.9%), brain (about 0.7%), nodes (about 4%), and peritoneum (about 2%) at the time of initial diagnosis. In 1987, the large bowel cancers found regionally or at distant sites at the time of diagnosis were about 26% and about 18%, respectively.... Surgery is the mainstay of treatment for colorectal cancer but recurrence is frequent. Colorectal cancer has proven resistant to chemotherapy, although limited success has been achieved using a combination of 5-fluorouracil and levamisole. Surgery has had the largest impact on survival and, in some patients with limited disease, achieves a cure. However, surgery removes bulk tumor, leaving behind microscopic residual disease which ultimately results in recrudescence. Overall recurrence rates for colonic tumors are about 33% and for rectal cancer about 42%. Of these recurrences, about 9%, are local, about 13% are systemic metastatic disease, and
Patents 383
the remaining 88% are a combination of local and systemic disease. Fifty percent of patients with recurrent colorectal cancer have hepatic metastases. Web site: http://www.delphion.com/details?pn=US05879656__ ·
Noninvasive detection of colorectal cancer and other gastrointestinal pathology Inventor(s): Nair; Padmanabhan P. (4520 Hemlock Coneway, Ellicott City, MD 21042) Assignee(s): none reported Patent Number: 6,534,280 Date filed: March 30, 2000 Abstract: A method for isolating viable, biologically substantially pure exfoliated fecal colonocytes at normal ambient temperature is described. Immunocoprocytes and inflammatory cells indicative of certain gastrointestinal conditions and a noninvasive method for detecting colorectal cancer are set forth. Composition of transport and suspension media for isolation of colonocytes are detailed. Excerpt(s): The present invention is related to isolated colonocytes enabling early noninvasive detection of colorectal cancer and other gastrointestinal diseases. More particularly, the present invention is related to isolated, biologically substantially pure and viable immunocoprocytes and nonepithelial cells of lymphoid origin obtained from a small fecal sample. The invention is further related to providing a transport medium and a dispersion or suspension medium for isolating viable colonocytes from a fecal sample at normal ambient temperature and a method for detecting colorectal and other gastrointestinal pathology employing the isolated colonocytes of the present invention. The isolated colonocytes also allow the study and determination of other anomalous conditions, symptoms, disorders or pathological conditions.... A common gastrointestinal malignancy in humans is colorectal cancer. It has been estimated that colorectal cancer accounts for approximately 14% of all cancer-related deaths in men and women in the United States and its incidence continues to be high (Boring et al, CA Cancer J. Clin. 1994; 44:7-26). Early detection is a critical factor in successful treatment of this cancer, as it is in the treatment of other malignancies.... Screening approaches to detection of colon and colorectal tumors are presently based on the use of (a) fecal occult blood test (FOBT), (b) flexible sigmoidoscopy, (c) double contrast barium enema, and (d) colonoscopy. Among these screening tests only FOBT, which is based on a relatively high probability of bleeding from colorectal tumors, is noninvasive, simple and relatively inexpensive. However, frequent false positive and false negative results of the FOBT considerably limit its specificity and sensitivity. Other procedures are expensive and invasive. Hence, there is a clear need for providing a simple, noninvasive, reliable and inexpensive method for detecting colorectal cancer, gastrointestinal (GI) tract diseases and other pathological conditions. Web site: http://www.delphion.com/details?pn=US06534280__
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Prevention and treatment of colorectal cancer by 6-fluoroursodeoxycholic acid (6FUDCA) Inventor(s): Gibson; Joyce Corey (Harding Township, NJ), Capuano; Leonard Robert (Parsippany, NJ) Assignee(s): Novartis AG (Basel, CH) Patent Number: 6,426,340 Date filed: October 6, 2000 Abstract: Methods for the prevention and treatment of colorectal cancer are provided. Specifically, the method relates to the administration of an effective adenoma or microadenoma preventing amount of 6-fluoroursodeoxycholic acid (6-FUDCA) or a pharmaceutically acceptable salt or pharmaceutically acceptable conjugate thereof to a mammal in need of such treatment. The methods find general use in the prevention of the formation of secondary bile acids, the reduction of deoxycholic acid, and the protection against cytotoxic effects of other bioacids and carcinogens. Excerpt(s): The invention relates to the treatment and prevention of precancerous cell formation in the colon in those patients at risk for developing such precancerous cells. It also relates to preventing recurrence of such cell formation in those having been treated for cancer of the colon.... Cancer of the colon is a common and deadly disease in the Western world. Genetic predisposition plays an important role, but exposure to substances that initiate and promote cancer is essential for a malignant tumor to develop. Bile acids have been implicated as important cancer-promoting agents.... In the normal colon mucosa, epithelial cells line crypt along the mucosal wall. Those epithelial cells which line the colon exposed surface and approximately the upper 2/3 of the crypt are normally non-proliferating, while those lining the lower 1/3 of the crypts are proliferating. As the proliferating cells migrate toward the upper portion of the crypt they transform and lose their proliferative ability. Ultimately the oldest cells are shed from the colon surface in the normal functioning of the colon. However, when the proliferating epithelial cells are induced to retain their proliferative capacity after reaching the upper 1/3 of the crypt, the normal process may go awry and microadenomas form. The proliferating cell, now at the surface of the colon continues to proliferate and a polyp develops. Web site: http://www.delphion.com/details?pn=US06426340__
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Screening test for early detection of colorectal cancer Inventor(s): Yeung; Ka Sing (810 Srigley St., Newmarket, CA), Kandel; Gabor P. (430 Heath St. East, Toronto, CA), Krepinsky; Jiri J. (810 Srigley Street, Newmarket, CA), Chociej; Jacek (43 Valleywoods Rd. #89, Toronto, CA) Assignee(s): none reported Patent Number: 5,416,025 Date filed: August 31, 1994 Abstract: A method for detecting the presence of neoplasia or cancer of the colon or rectum, which method comprises obtaining a sample of colorectal mucus from the rectum of a patient; treating the sample with Schiff's reagent and screening for neoplasia or cancer of the colon or rectum based upon the coloration produced in the sample by the treatment. The method is rapid, simple, inexpensive and provides a screening test
Patents 385
for colorectal cancer which does not give a high percentage of false positive and false negative results. A screening test kit is provided. Excerpt(s): This invention relates to a simple screening test for colorectal cancer. Specifically, a method is described whereby a colorectal cancer marker is detected in rectal mucus obtained by digital rectal examination. More particularly, this marker is detected in the mucus deposited on a support using Schiff's reagent.... Colorectal carcinoma is the second most frequent cause of cancer mortality in men and women, causing nearly one third of all malignancy-related deaths in North America. It has been estimated that ultimately as many as 6% of Canadians and Americans will develop malignancy in the lower bowel, and over 50% of them will die within 5 years of diagnosis. Because there are no realistic prospects of significantly improving the cure rate once the cancer has spread beyond the bowel wall, many authorities believe that colorectal cancer can be controlled only by preventive measures (1).... Primary prevention, i.e. averting the development of the tumour by altering biological risk factors, is not yet feasible since so little is understood of the etiology of the disease. Alternatively, secondary preventive measures, i.e. detection at an asymptomatic, treatable state, would be possible should an effective screening test be available. Indeed, neoplasms of the lower bowel have the characteristics that make them a suitable candidate for the development of a screening test. This is because i) it is a common cause of cancer-related deaths, and ii) whereas once the stage of true cancer is reached, leading to symptoms, the mortality rate is over 50%, removal of bowel neoplasms at its earliest, asymptomatic stage can be done by non-surgical endoscopic polypectomy, without any significant risk. Moreover, it requires at least four to six years before an adenomatous polyp reaches the cancer stage, so there is ample opportunity to detect these neoplasms at their treatable stage. Recent clinical studies document a decrease in mortality from colorectal cancer screening, as predicted by these theoretical considerations. The problem to-date has been that polyps can be reliably detected only by endoscopy. Web site: http://www.delphion.com/details?pn=US05416025__ ·
Treatment of pain and colorectal cancer with dipeptoids of.alpha.-substituted TrpPhe derivatives Inventor(s): Aranda; Julian (Vorstetter, DE), Roberts; Edward (Wood Ditton, GB2), Pritchard; Martyn C. (Swavesey, GB2), Horwell; David C. (Foxton, GB2), Richardson; Reginald S. (Haverhill, GB2) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 5,580,896 Date filed: May 22, 1995 Abstract: This invention relates to the treatment of pain and inhibiting the growth of colorectal cancer with dipeptoids of.alpha.-substituted Trp-Phe derivatives. Excerpt(s): Agents acting at central cholecystokinin (CCK) receptors induce satiety (Schick, Yaksh and Go, Regulatory Peptides 14:277-291, 1986). They are also expected to act as analgesics (Hill, Hughes and Pittaway, Neuropharmacology 26:289-300, 1987), and as anticonvulsants (MacVicar, Kerrin and Davison, Brain Research, 406:130-135, 1987).... Reduced levels of CCK-peptides have been found in the brains of schizophrenic patients compared with controls (Roberts, Ferrier, Lee, Crow, Johnstone, Owens, BacareseHamilton, McGregor, O'Shaughnessey, Polak and Bloom. Brain Research 288, 199-211, 1983). It has been proposed that changes in the activity of CCK neurones projecting to
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the nucleus accumbens may play a role in schizophrenic processes by influencing dopaminergic function (Totterdell and Smith, Neuroscience 19, 181-192, 1986). This is consistent with numerous reports that CCK peptides modulate dopaminergic function in the basal ganglia and particularly the nucleus accumbens (Weiss, Tanzer, and Ettenberg, Pharmacology, Biochemistry and Behaviour 30, 309-317, 1988; Schneider, Allpert and Iversen, Peptides 4, 749-753, 1983). It may therefore be expected that agents modifying CCK receptor activity may have therapeutic value in conditions associated with disturbed function of central dopaminergic function such as schizophrenia and Parkinson's disease.... The CCK peptides are widely distributed in various organs of the body including the gastrointestinal tract, endocrine glands, and the nerves of the peripheral and central nervous systems. Various biologically active forms have been identified including a 33-amino acid hormone and various carboxyl-terminus fragments of this peptide (e.g., the octapeptide CCK26-33 and the tetrapeptide CCK30-33). (G. J. Dockray, Br. Med. Bull., 38 (No. 3):253-258, 1982). Web site: http://www.delphion.com/details?pn=US05580896__ ·
Use of 2-hydroxy-5-phenylazobenzoic acid chemopreventative and chemotherapeutic agents
derivatives
as
colon
cancer
Inventor(s): Johnson; Lorin K. (Pleasanton, CA), Sleisenger; Marvin H. (Kentfield, CA), Johnson; Lorin K. (Pleasanton, CA), Sleisenger; Marvin H. (Kentfield, CA) Assignee(s): Salix Pharmaceuticals, Inc. (Palo Alto, CA), Salix Pharmaceuticals, Inc. (Palo Alto, CA) Patent Number: 5,905,073 Date filed: July 11, 1996 Abstract: The present invention provides a method of colon cancer chemoprevention or chemotherapy comprising administering to an individual suffering from colon cancer or at risk to develop colon cancer a pharmaceutical composition comprising an effective amount of a 2-hydroxy-5-phenylazobenzoic acid derivative or an ester of an active metabolite or an oxidation product of an active metabolite thereof, or a pharmacologically acceptable salt of the 2-hydroxy-5-phenylazobenzoic acid derivative or an ester or an active metabolite or an oxidation product of an active matabolite thereof. Excerpt(s): This invention is related to colon cancer chemoprevention and chemotherapy.... This invention is related to colon cancer chemoprevention and chemotherapy.... Colon cancer currently accounts for 11% of all deaths due to malignancy annually in the United States. With an incidence of 62 per 100,000 and a prevalence of 300 per 100,000, the disease is currently the third leading cause of death in men and the fourth leading cause of death in women. Colon cancer has a particularly poor five-year survival rate of less than 50%, due to the late stage at which diagnosis is generally made. The currently favored treatment, surgery combined with chemotherapy, has failed to increase this survival rate. What is needed is a safe and effective preventive therapy which could be initiated early in patient populations known to be at an increased risk of developing colon cancer.... Colon cancer currently accounts for 11% of all deaths due to malignancy annually in the United States. With an incidence of 62 per 100,000 and a prevalence of 300 per 100,000, the disease is currently the third leading cause of death in men and the fourth leading cause of death in women. Colon cancer has a particularly poor five-year survival rate of less than 50%, due to the late stage at which diagnosis is generally made. The currently favored treatment,
Patents 387
surgery combined with chemotherapy, has failed to increase this survival rate. What is needed is a safe and effective preventive therapy which could be initiated early in patient populations known to be at an increased risk of developing colon cancer.... Eicosanoids and Differentiated Functions of Gastrointestinal Cells. Eicosanoids are significant regulators of gastrointestinal epithelial cell growth, differentiation and function. Eicosanoid products of the prostaglandin series are known to induce mucus secretion (Beckel and Kauffman (1981) Gastroenterology 80:770-776) and the secretion of electrolytes and fluid (Miller (1983) Am. J. Physiol. 245:G601-G623). They also induce active transport (Bukhave and Rask-Madsen (1980) Gastroenterology 78:32-37) and increase the replicative capacity of the epithelium (Konturek et al. (1981) Gastroenterology 80:1196-1201). These responses result in the maintenance of a differentiated, protective barrier system of tightly joined epithelial cells whose apical surface are covered by a dense glyco-conjugate chemical buffer. In the stomach and upper duodenum such a barrier protects against the acidic and proteolytic environment elaborated for digestion, while in the colon it protects against the invasion of bacteria and toxins. It is therefore not surprising that exogenous, synthetic prostaglandins are actively cytoprotective (Whittle and Vane (1987) In: Johnson (ed.) PHYSIOLOGY OF THE GASTROINTESTINAL TRACT, Vol. 1, 2nd ed., New York: Raven Press, pp. 143180) and have found therapeutic utility as secondary anti-ulcer treatments. The gastrointestinal ("GI") system has therefore evolved to actively produce and rely on a specific differentiated complement of eicosanoid products present in the local environment. As all eicosanoids are derived from the common precursor arachidonic acid, which is itself liberated from membrane phospholipids, GI mucosal cells have a relatively high basal level of arachidonate turnover initiated by the enzyme phospholipase A.sub.2 (PLA.sub.2).... Eicosanoids and Differentiated Functions of Gastrointestinal Cells. Eicosanoids are significant regulators of gastrointestinal epithelial cell growth, differentiation and function. Eicosanoid products of the prostaglandin series are known to induce mucus secretion (Beckel and Kauffman (1981) Gastroenterology 80:770-776) and the secretion of electrolytes and fluid (Miller (1983) Am. J. Physiol. 245:G601-G623). They also induce active transport (Bukhave and RaskMadsen (1980) Gastroenterology 78:32-37) and increase the replicative capacity of the epithelium (Konturek et al. (1981) Gastroenterology 80:1196-1201). These responses result in the maintenance of a differentiated, protective barrier system of tightly joined epithelial cells whose apical surface are covered by a dense glyco-conjugate chemical buffer. In the stomach and upper duodenum such a barrier protects against the acidic and proteolytic environment elaborated for digestion, while in the colon it protects against the invasion of bacteria and toxins. It is therefore not surprising that exogenous, synthetic prostaglandins are actively cytoprotective (Whittle and Vane (1987) In: Johnson (ed.) PHYSIOLOGY OF THE GASTROINTESTINAL TRACT, Vol. 1, 2nd ed., New York: Raven Press, pp. 143-180) and have found therapeutic utility as secondary anti-ulcer treatments. The gastrointestinal ("GI") system has therefore evolved to actively produce and rely on a specific differentiated complement of eicosanoid products present in the local environment. As all eicosanoids are derived from the common precursor arachidonic acid, which is itself liberated from membrane phospholipids, GI mucosal cells have a relatively high basal level of arachidonate turnover initiated by the enzyme phospholipase A.sub.2 (PLA.sub.2). Web site: http://www.delphion.com/details?pn=US05905073__
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Patent Applications on Colon Cancer As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to colon cancer: ·
Colon and colon cancer associated polynucleotides and polypeptides Inventor(s): Birse, Charles E. (North Potomac, MD), Rosen, Craig A. (Laytonsville, MD), Barash, Steve C. (Rockville, MD), Ruben, Steven M. (Olney, MD) Correspondence: HUMAN GENOME SCIENCES INC; 9410 KEY WEST AVENUE; ROCKVILLE; MD; 20850 Patent Application Number: 20030109690 Date filed: March 27, 2002 Abstract: The present invention relates to novel colon or colon cancer related polynucleotides and the polypeptides encoded by these polynucleotides herein collectively known as "colon or colon cancer antigens," and the use of such colon or colon cancer antigens for detecting disorders of the colon, particularly the presence of colon cancer and colon cancer metastases. More specifically, isolated colon or colon cancer associated nucleic acid molecules are provided encoding novel colon or colon cancer associated polypeptides. Novel colon or colon cancer polypeptides and antibodies that bind to these polypeptides are provided. Also provided are vectors, host cells, and recombinant and synthetic methods for producing human colon or colon cancer associated polynucleotides and/or polypeptides. The invention further relates to diagnostic and therapeutic methods useful for diagnosing, treating, preventing and/or prognosing disorders related to the colon, including colon cancer, and therapeutic methods for treating such disorders. The invention further relates to screening methods for identifying agonists and antagonists of polynucleotides and polypeptides of the invention. The present invention further relates to methods and/or compositions for inhibiting the production and function of the polypeptides of the present invention. Excerpt(s): This application is a continuation-in-part of, and claims priority under 35 U.S.C..sctn.120 to International Application No: PCT/US00/26524, filed Sep. 28, 2000, which claims benefit under 35 U.S.C..sctn.119(e) of U.S. Provisional Application Nos. 60/157,137, filed on Sep. 29, 1999, and 60/163,280, filed on Nov. 3, 1999. Each of the above referenced applications is hereby incorporated by reference herein in its entirety.... The present invention relates to novel colon and colon cancer related polynucleotides, the polypeptides encoded by these polynucleotides herein collectively referred to as "colon or colon cancer antigens," and antibodies that immunospecifically bind these polypeptides, and the use of such colon or colon cancer polynucleotides, antigens, and antibodies for detecting, treating, preventing and/or prognosing disorders of the colon, including, but not limited to, the presence of colon cancer and colon cancer metastases. More specifically, isolated colon or colon cancer nucleic acid molecules are provided encoding novel colon or colon cancer polypeptides. Novel colon or colon cancer polypeptides and antibodies that bind to these polypeptides are provided. Also provided are vectors, host cells, and recombinant and synthetic methods for producing human colon or colon cancer polynucleotides, polypeptides, and/or antibodies. The invention further relates to diagnostic and therapeutic methods useful
10
This has been a common practice outside the United States prior to December 2000.
Patents 389
for diagnosing, treating, preventing and/or prognosing disorders related to the colon, including colon cancer, and therapeutic methods for treating such disorders. The invention further relates to screening methods for identifying agonists and antagonists of polynucleotides and polypeptides of the invention. The invention further relates to methods and/or compositions for inhibiting or promoting the production and/or function of the polypeptides of the invention.... The human colon, a portion of the large intestine, extends from the end of the small intestine and cecum up the right side of the abdomen (ascending colon), across to the left side (transverse colon), down the left side (descending colon), and loops (simoid flexure or sigmoid colon) to join the rectum. In humans, the colon has no digestive function, but instead lubricates waste products, adsorbs remaining fluids and salts, and stores waste products unti they are ready to be passed from the body. Most adsorption occurs in the ascending and transverse regions, where the liquid material received from the small intestine is dehydrated to form a fecal mass. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·
Colon cancer antigen panel Inventor(s): Stockert, Elisabeth; (New York, NY), Old, Lloyd J. (New York, NY), Chen, Yao-Tseng; (New York, NY), Scanlan, Matthew J. (New York, NY) Correspondence: WOLF GREENFIELD & SACKS, PC; FEDERAL RESERVE PLAZA; 600 ATLANTIC AVENUE; BOSTON; MA; 02210-2211; US Patent Application Number: 20030165834 Date filed: May 4, 2001 Abstract: The invention provides methods for diagnosing cancer including colon cancer, based on the identification of certain colon cancer-associated polypeptides as antigens that elicit immune responses in colon cancer. The identified antigens can be utilized as markers for diagnosing colon cancer, and for following the course of treatment of colon cancer. Excerpt(s): The invention relates to use of novel colon cancer-associated nucleic acid molecules and the polypeptides they encode as markers for cancer, including colon cancer. The invention also relates to the use of a panel of colon cancer-associated nucleic acid molecules and the polypeptides they encode and their use as markers for colon cancer. In addition, the invention relates to the use of such nucleic acid molecules and the polypeptides they encode for diagnosing colon cancer, and monitoring the colon cancer's response to treatment.... Colon cancer, which is also known as cancer of the large bowel and colorectal cancer, is second only to lung cancer as a cause of cancer death in the United States. Colorectal cancer is a common malignant condition that generally occurs in individuals 50 years of age or older; and the overall incidence rate of colon cancer has not changed substantially during the past 40 years. (Harrison's Principles of Internal Medicine, 14/e, McGraw-Hill Companies, New York, 1998). The treatment of colon cancer once diagnosis is made depends on the extent of the cancer's invasion of the colon tissue, lymph nodes, and metastasis to other organs such as the liver. The survival rate for patients diagnosed with early-stage cancer is about 90% survival after 5 years. The five-year survival rate drops if the cancer is not detected until the cancer has spread beyond the mucosal layer of the colon, and drops significantly further if, when detected, the cancer has spread beyond the colon to the lymph nodes and beyond. Thus, it is critical to diagnose colon cancer at the earliest possible stage to increase the likelihood of a positive prognosis and outcome.... The traditional method of
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colon cancer diagnosis is through the use of non-invasive or mildly invasive diagnostic tests, more invasive visual examination, and histologic examination of biopsy. Although these tests may detect colon cancers, each has drawbacks that limit its effectiveness as a diagnostic tool. One primary source of difficulty with most of the currently available methods for diagnosing colorectal cancer, is patient reluctance to submit to, or follow through with the procedures, due to the uncomfortable or perceived embarrassing nature of the tests. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·
Compositions and methods for the therapy and diagnosis of colon cancer Inventor(s): Jiang, Yuqiu; (Kent, WA), Stolk, John A. (Bothell, WA), Secrist, Heather; (Seattle, WA), King, Gordon E. (Shoreline, WA), Meagher, Madeleine Joy; (Seattle, WA) Correspondence: SEED INTELLECTUAL PROPERTY LAW GROUP PLLC; 701 FIFTH AVE; SUITE 6300; SEATTLE; WA; 98104-7092; US Patent Application Number: 20030129207 Date filed: August 20, 2002 Abstract: Compositions and methods for the therapy and diagnosis of cancer, particularly colon cancer, are disclosed. Illustrative compositions comprise one or more colon tumor polypeptides, immunogenic portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention and/or treatment of diseases, particularly colon cancer. Excerpt(s): The present invention relates generally to therapy and diagnosis of cancer, such as colon cancer. The invention is more specifically related to polypeptides, comprising at least a portion of a colon tumor protein, and to polynucleotides encoding such polypeptides. Such polypeptides and polynucleotides are useful in pharmaceutical compositions, e.g., vaccines, and other compositions for the diagnosis and treatment of colon cancer.... Cancer is a significant health problem throughout the world. Although advances have been made in detection and therapy of cancer, no vaccine or other universally successful method for prevention and/or treatment is currently available. Current therapies, which are generally based on a combination of chemotherapy or surgery and radiation, continue to prove inadequate in many patients.... Colon cancer is the second most frequently diagnosed malignancy in the United States as well as the second most common cause of cancer death. The five-year survival rate for patients with colorectal cancer detected in an early localized stage is 92%; unfortunately, only 37% of colorectal cancer is diagnosed at this stage. The survival rate drops to 64% if the cancer is allowed to spread to adjacent organs or lymph nodes, and to 7% in patients with distant metastases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 391
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Compositions and methods of diagnosing, monitoring, staging, imaging and treating colon cancer Inventor(s): Hu, Ping; (San Ramon, CA), Recipon, Herve E. (San Francisco, CA), Piderit, Alejandra; (Concepcion, CL), Yang, Fei; (San Diego, CA), Macina, Roberto A. (San Jose, CA) Correspondence: LICATA & TYRRELL P.C. 66 E. MAIN STREET; MARLTON; NJ; 08053; US Patent Application Number: 20020065396 Date filed: March 26, 2001 Abstract: The present invention provides polynucleotides and polypeptides which are diagnostic markers for colon cancer. In addition, antibodies immunospecific for these markers are provided. Vectors, hosts cells and methods for producing these markers, as well as methods and tools for using these markers in detecting, diagnosing, monitoring, staging, prognosticating, imaging and treating colon cancer are also provided. Excerpt(s): This application claims the benefit of priority from U.S. Provisional Application Ser. No. 60/192,667, filed Mar. 28, 2000.... This invention relates, in part, to newly identified polynucleotides and polypeptides encoded thereby, as well as methods for producing and using these polynucleotides and polypeptides. Antibodies which are immunospecific for these polypeptides are also described. Expression of the newly identified polynucleotides and levels of the polypeptides encoded thereby are upregulated in or specific to colon cancer tissue. These new polynucleotides and polypeptides, referred to herein as Colon Cancer Specific Genes or CSGs are believed to be useful in assays for detecting, diagnosing, monitoring, staging, prognosticating, imaging and treating cancers, particularly colon cancer.... Cancer of the colon is a highly treatable and often curable disease when localized to the bowel. It is one of the most frequently diagnosed malignancy in the United States as well as the second most common cause of cancer death. Surgery is the primary treatment and results in cure in approximately 50% of patients. However, recurrence following surgery is a major problem and often is the ultimate cause of death. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Compositions, kits, and methods for identification, assessment, prevention, and therapy of colon cancer Inventor(s): Morrissey, Michael P. (Brighton, MA), Bryant, Barbara Moore; (Cambridge, MA), Guillemette, Tracy L. (Waltham, MA), Berger, Allison; (Watertown, MA), Schlegel, Robert; (Auburndale, MA) Correspondence: LAHIVE & COCKFIELD; 28 STATE STREET; BOSTON; MA; 02109; US Patent Application Number: 20030148314 Date filed: August 1, 2002 Abstract: The invention relates to newly discovered nucleic acid molecules and proteins associated with colon cancer. Compositions, kits, and methods for detecting, characterizing, preventing, and treating human colon cancers are provided. Excerpt(s): The present application claims priority from U.S. provisional patent application serial No. 60/309,415, filed on Aug. 1, 2001, and from U.S. provisional patent
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application serial No. 60/330,233, filed on Oct. 17, 2001. The present application also claims priority from U.S. provisional patent application serial No. 60/309,458, filed on Aug. 1, 2001. All of the above applications are expressly incorporated by reference.... The field of the invention is colon cancer, including diagnosis, characterization, management, and therapy of colon cancer, particularly metastatic colon cancer.... The increased number of cancer cases reported in the United States, and, indeed, around the world, is a major concern. Currently there are only a handful of detection and treatment methods available for specific types of cancer, and these provide no absolute guarantee of success. In order to be most effective, these treatments require not only an early detection of the malignancy, but also a reliable assessment of the severity of the malignancy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·
Compounds for immunotherapy and diagnosis of colon cancer and methods for their use Inventor(s): Clapper, Jonathan D. (Seattle, WA), Skeiky, Yasir A.W. (Bellevue, WA), Fanger, Gary R. (Mill Creek, WA), Vedvick, Thomas S. (Federal Way, WA), Carter, Darrick; (Seattle, WA), Wang, Tongtong; (Medina, WA), Wang, Aijun; (Issaquah, WA), Secrist, Heather; (Seattle, WA), King, Gordon E. (Shoreline, WA), Smith, Carole L. (Seattle, WA), Lodes, Michael J. (Seattle, WA), Benson, Darin R. (Seattle, WA), Meagher, Madeleine Joy; (Seattle, WA), Stolk, John A. (Bothell, WA), Jiang, Yuqiu; (Kent, WA), Xu, Jiangchun; (Bellevue, WA) Correspondence: SEED INTELLECTUAL PROPERTY LAW GROUP PLLC; 701 FIFTH AVE; SUITE 6300; SEATTLE; WA; 98104-7092; US Patent Application Number: 20020182191 Date filed: December 19, 2001 Abstract: Compositions and methods for the therapy and diagnosis of cancer, such as colon cancer, are disclosed. Compositions may comprise one or more colon tumor proteins, immunogenic portions thereof, or polynucleotides that encode such portions. Alternatively, a therapeutic composition may comprise an antigen presenting cell that expresses a colon tumor protein, or a T cell that is specific for cells expressing such a protein. Such compositions may be used, for example, for the prevention and treatment of diseases such as colon cancer. Diagnostic methods based on detecting a colon tumor protein, or mRNA encoding such a protein, in a sample are also provided. Excerpt(s): The present invention relates generally to therapy and diagnosis of cancer, such as colon cancer. The invention is more specifically related to polypeptides comprising at least a portion of a colon tumor protein, and to polynucleotides encoding such polypeptides. Such polypeptides and polynucleotides may be used in vaccines and pharmaceutical compositions for prevention and treatment of colon cancer, and for the diagnosis and monitoring of such cancers.... Cancer is a significant health problem throughout the world. Although advances have been made in detection and therapy of cancer, no vaccine or other universally successful method for prevention or treatment is currently available. Current therapies, which are generally based on a combination of chemotherapy or surgery and radiation, continue to prove inadequate in many patients.... Colon cancer is the second most frequently diagnosed malignancy in the United States as well as the second most common cause of cancer death. The five-year survival rate for patients with colorectal cancer detected in an early localized stage is 92%; unfortunately, only 37% of colorectal cancer is diagnosed at this stage. The survival
Patents 393
rate drops to 64% if the cancer is allowed to spread to adjacent organs or lymph nodes, and to 7% in patients with distant metastases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·
Genes expressed in colon cancer Inventor(s): Sornasse, Thierry; (Mountain View, CA), Lasek, Amy K.W. (Oakland, CA) Correspondence: LEGAL DEPARTMENT; INCYTE GENOMICS, INC. 3160 PORTER DRIVE; PALO ALTO; CA; 94304; US Patent Application Number: 20030073105 Date filed: May 29, 2002 Abstract: The present invention relates to a combination comprising a plurality of cDNAs which are differentially expressed in colon cancer and which may be used in their entirety or in part as to diagnose, to stage to treat or to monitor the progression or treatment of colon cancer. Excerpt(s): This application claims benefit of provisional application Serial No. 60/295,239, filed May 31, 2001.... The present invention relates to a combination comprising a plurality of cDNAs which are differentially expressed in colon cancer and which may be used entirely or in part to diagnose, to stage, to treat, or to monitor the progression or treatment of colon cancer.... Colorectal cancer is the fourth most common cancer and the second most common cause of cancer death in the United States with approximately 130,000 new cases and 55,000 deaths per year. Colon and rectal cancers share many environmental risk factors, and both are found in individuals with specific genetic syndromes. (For a review of colorectal cancer, see Potter (1999) J Natl Cancer Inst 91:916-932.) Colon cancer is the only cancer that occurs with approximately equal frequency in men and women, and the five-year survival rate following diagnosis of colon cancer is around 55% in the United States (Ries et al. (1990) National Institutes of Health, DHHS Publ No (NIH)90-2789). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Metastatic breast and colon cancer regulated genes Inventor(s): Giese, Klaus; (Berlin, DE) Correspondence: Chiron Corporation; Intellectual Property, R338; P.O. Box 8097; Emeryville; CA; 94662-8097; US Patent Application Number: 20030158109 Date filed: September 5, 2002 Abstract: Gene sequences as shown in SEQ ID NOS: 1-85 have been found to be significantly associated with metastatic potential of cancer cells, especially breast and colon cancer cells. Methods are provided for determining the risk of metastasis of a tumor, which involve determining whether a tissue sample from a tumor expresses a polypeptide encoded by a gene as shown in SEQ ID NOS: 1-85, or a substantial portion thereof. Excerpt(s): This invention relates to methods for predicting the behavior of tumors. More particularly, the invention relates to methods in which a tumor sample is
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examined for expression of a specified gene sequence thereby to indicate propensity for metastatic spread.... It is an object of the present invention to provide markers for distinguishing between tumors which will or have metastasized and those which are less likely to metastasize. These and other objects of the invention are provided by one or more of the embodiments described below.... One embodiment of the invention provides an isolated and purified human protein having an amino acid sequence which is at least 85% identical to an amino acid sequence encoded by a nucleotide sequence selected from the group consisting of SEQ ID NOS: 1-63 or the complement thereof. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·
Method of detecting colon cancer Inventor(s): Fagoaga, Omar; (Colton, CA), Kelln, Wayne; (Loma Linda, CA), McCracken, John D. (Redlands, CA), Pant, Keshab D. (Perris, CA), Nehlsen-Cannarella, Sandra; (Redlands, CA) Correspondence: KNOBBE MARTENS OLSON & BEAR LLP; 620 NEWPORT CENTER DRIVE; SIXTEENTH FLOOR; NEWPORT BEACH; CA; 92660; US Patent Application Number: 20020009760 Date filed: July 25, 2001 Abstract: An immunological assay and kit for colon cancer screening is disclosed. Fecal glycoproteins are extracted from individual samples such that immunogenicity is maintained. The purified fecal glycoproteins are reacted with antibodies to Colon and Ovarian Tumor Antigen (COTA). The mucin antigen COTA is specifically present in colorectal cancer tissue and not in normal colons. The amount of COTA in the fecal sample is determined and used to indicate the presence of colon cancer. Excerpt(s): The present invention is directed to a method for detecting colon cancer utilizing an antibody specific for a glycoprotein found in colon cancer cells.... Colorectal cancer is among the leading causes of cancer-related morbidity and mortality in industrialized nations. The pathogenesis is related to hereditary influences, modified by the quantity and quality of dietary fat. In 1995, the American Cancer society estimated that 135,000 new cases of colon cancer were diagnosed; 71% were in the colon and 30% were in the rectum. Patients diagnosed at an early stage, prior to lymph-node spread, are potentially cured with surgery. At present, only 41% of patients are diagnosed at an early stage. The remaining cases frequently undergo peri-operative radiation and/or chemotherapy to attempt to control the metastatic spread of disease. Ultimately, 50% of patients thought to have undergone curative resections eventually develop recurrent disease. Unfortunately, 55,000 Americans die each year due to recurrent or metastatic colon or rectal cancer. The key to enhanced survival is early diagnosis. Colon and rectal cancers are often silent and slowly progressive. Most patients exhibit symptoms such as rectal bleeding, pain, abdominal distension or weight loss only after the disease is advanced and not surgically curable.... Over the past 25 years, early colorectal cancer detection has been based on the fecal occult blood test (FOBT) performed annually on asymptomatic individuals. Current recommendations adapted by several healthcare organizations, including the American Cancer Society, call for fecal occult blood testing beginning at age 50, repeated annually until such time as the patient would no longer benefit from screening. A positive FOBT leads to colonoscopic examination of the bowel; an expensive and invasive procedure, with a serious complication rate of one per 5,000 examinations. Only 12% of patients with heme positive stool are diagnosed with cancer or large polyps at the time of colonoscopy. Most studies show that FOBT screening does
Patents 395
not improve cancer-related mortality or overall survival. Compliance with occult blood testing has been poor; less than 20 percent of the population is offered or completes FOBT as recommended. If FOBT is properly done, the patient collects a fecal sample from three consecutive bowel movements. Samples are obtained while the patient adheres to dietary guidelines and avoids medications known to induce occult gastrointestinal bleeding. In reality, physicians frequently fail to instruct patients properly, patients frequently fail to adhere to protocol, and some patients find the task of collecting fecal samples difficult or unpleasant, hence compliance with annual occult blood testing is poor. Compounding the problem of compliance, the sensitivity and specificity of FOBT to detect colon cancer is poor. In eight prospective studies where hemoccult testing was followed by colonoscopy, only 41 of 159 cancers diagnosed were detected by FOBT, yielding a screening sensitivity of 26%. FOBT sensitivity for precancerous polyps was also poor. Poor test specificity leads to unnecessary colonoscopy, adding considerable expense to colon cancer screening. In the University of Minnesota trial, a large prospective hemoccult screening study, test specificity was 90%, and positive predictive value was 2%. Only one colon cancer was found in every 50 testtriggered colonoscopies performed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·
Method of detection and treatment of colon cancer by analysis of beta-cateninsensitive isoforms of lymphoid enhancer factor-1 Inventor(s): Holcombe, Randall F. (Cotode Caza, CA), Hung Li, Tony Wai; (Los Angeles, CA), Marsh, J. Lawrence; (Newport Beach, CA), Waterman, Marian L. (Irvine, CA), Hovanes, Karine; (Westminster, CA) Correspondence: Lisa A. Haile, Ph.D. Gray Cary Ware & Freidenrich LLP; Suite 1100; 4365 Executive Drive; San Diego; CA; 92121-2133; US Patent Application Number: 20020169300 Date filed: January 29, 2002 Abstract: The present invention relates to the discovery that LEF1 is a new type of target gene in that it is ectopically activated in colon cancer. The pattern of this ectopic expression is unusual because it derives from selective activation of a promoter for a full-length LEF1 isoform that binds.beta.-catenin, but not a second, intronic promoter that drives expression of a dominant negative isoform..beta.-catenin/TCF complexes can activate the promoter for full-length LEF1 suggesting that in cancer, high levels of these complexes misregulate transcription to favor a positive feedback loop for Wnt signaling by inducing selective expression of full length,.beta.-catenin sensitive forms of LEF/TCFs. The invention provides diagnostic and therapeutic methodologies based on the discoveries described herein. Excerpt(s): This application claims priority under 35 U.S.C..sctn.119(e) to U.S. Provisional Patent Application Ser. No. 60/265,264, filed Jan. 30, 2001, the entire contents of which is incorporated herein by reference.... The invention relates generally to cancer diagnostics and therapeutics and, more specifically, to aberrant activation and expression of lymphoid enhancer factor (LEF1) in colon cancer.... Constitutive activation of the Wnt signaling pathway is a root cause of many colon cancers.sup.1-3. Activation of the pathway is caused by genetic mutations that stabilize the.beta.-catenin protein, allowing it to accumulate in the nucleus and form complexes with any of the four members of the lymphoid enhancer factor (LEF1) and T-cell factor (TCF1, TCF3, TCF4) family of transcription factors (referred to collectively as LEF/TCFs) to activate
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transcription of target genes.sup.3, 4. Target genes such as MYC, CCND1, MMP-7, and TCF7 (refs. 5-9) are normally expressed in colon tissue, so it is proposed that abnormal expression levels or patterns imposed by.beta.-catenin/TCF complexes play a role in tumor progression. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·
Methods of diagnosis of colorectal cancer, compositions and methods of screening for colorectal cancer modulators Inventor(s): Wilson, Keith E. (Menlo Park, CA), Mack, David H. (San Francisco, CA), Gish, Kurt C. (Redwood City, CA) Correspondence: TOWNSEND AND TOWNSEND AND CREW, LLP; TWO EMBARCADERO CENTER; EIGHTH FLOOR; SAN FRANCISCO; CA; 94111-3834; US Patent Application Number: 20030077568 Date filed: August 14, 2001 Abstract: Described herein are methods that can be used for diagnosis and prognosis of colorectal cancer. Also described herein are methods that can be used to screen candidate bioactive agents for the ability to modulate colorectal cancer. Additionally, methods and molecular targets (genes and their products) for therapeutic intervention in colorectal and other cancers are described. Excerpt(s): This application is a continuation in part of U.S. patent application Ser. No. 09/663,733 filed Sep. 15, 2000, which is incorporated herein by reference in its entirety.... The invention relates to the identification of expression profiles and the nucleic acids involved in colorectal cancer, and to the use of such expression profiles and nucleic acids in diagnosis and prognosis of colorectal cancer. The invention further relates to methods for identifying and using candidate agents and/or targets which modulate colorectal cancer.... Cancer of the colon and/or rectum (referred to as "colorectal cancer") are significant in Western populations and particularly in the United States. Cancers of the colon and rectum occur in both men and women most commonly after the age of 50. These develop as the result of a pathologic transformation of normal colon epithelium to an invasive cancer. There have been a number of recently characterized genetic alterations that have been implicated in colorectal cancer, including mutations in two classes of genes, tumor-suppressor genes and proto-oncogenes, with recent work suggesting that mutations in DNA repair genes may also be involved in tumorigenesis. For example, inactivating mutations of both alleles of the adenomatous polyposis coli (APC) gene, a tumor suppressor gene, appears to be one of the earliest events in colorectal cancer, and may even be the initiating event. Other genes implicated in colorectal cancer include the MCC gene, the p53 gene, the DCC (deleted in colorectal carcinoma) gene and other chromosome 18q genes, and genes in the TGF-.beta. signaling pathway. For a review, see Molecular Biology of Colorectal Cancer, pp. 238299, in Curr. Probl. Cancer, September/October 1997; see also Willams, Colorectal Cancer (1996); Kinsella & Schofield, Colorectal Cancer: A Scientific Perspective (1993); Colorectal Cancer: Molecular Mechanisms, Premalignant State and its Prevention (Schmiegel & Scholmerich eds., 2000); Colorectal Cancer: New Aspects of Molecular Biology and Their Clinical Applications (Hanski et al., eds 2000); McArdle et al., Colorectal Cancer (2000); Wanebo, Colorectal Cancer (1993); Levin, The American Cancer Society: Colorectal Cancer (1999); Treatment of Hepatic Metastases of Colorectal Cancer (Nordlinger & Jaeck eds., 1993); Management of Colorectal Cancer (Dunitz et al., eds. 1998); Cancer: Principles and Practice of Oncology (Devita et al., eds. 2001); Surgical
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Oncology: Contemporary Principles and Practice (Kirby et al., eds. 2001); Offit, Clinical Cancer Genetics: Risk Counseling and Management (1997); Radioimmunotherapy of Cancer (Abrams & Fritzberg eds. 2000); Fleming, AJCC Cancer Staging Handbook (1998); Textbook of Radiation Oncology (Leibel & Phillips eds. 2000); and Clinical Oncology (Abeloff et al., eds. 2000). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·
Methods of treating colon cancer utilizing tumor-specific antibodies Inventor(s): Old, Lloyd J. (New York, NY), Welt, Sydney; (New York, NY) Correspondence: FULBRIGHT & JAWORSKI, LLP; 666 FIFTH AVE; NEW YORK; NY; 10103-3198; US Patent Application Number: 20030031671 Date filed: August 1, 2001 Abstract: This invention relates to methods of reducing the effects of colon cancer tumors. Various agents are conjugated to PEG(polyethylene glycol)-conjugated antibody which are specific for colon cancer cells. The conjugates are administered to patients having colon cancer such that the effects of the cancer are reduced. Excerpt(s): This invention relates to a method of reducing the effects of colon cancers, utilizing at least one monoclonal antibody conjugated to PEG. Specifically, at least one PEG conjugated monoclonal antibody is utilized in conjunction with an anti-tumor drug, a peptide which inhibits DNA tumor activity or a radioisotope in the treatment of colorectal carcinoma. This invention further relates to a method of delivering genetic material to DNA of tumor cells and to a method of delivering anti-cancer agents to nuclei of colon tumor cells, as well as to PEG conjugated monoclonal antibodies which are specific for A33 antigen; an antigen found on colon cancer cells.... Colorectal carcinoma is a malignant neoplastic disease. There is a high incidence of colorectal carcinoma in the Western world, particularly in the United States. Tumors of this type often metastasize through lymphatic and vascular channels. Many patients with colorectal carcinoma eventually die from this disease. In fact, it is estimated that 62,000 persons in the United States alone die of colorectal carcinoma annually.... To date, systemic therapies and chemotherapies have been developed for the treatment of colorectal cancer. However, no therapies have exhibited sufficient anti-tumor activity to prolong the survival of colorectal carcinoma patients with metastatic disease with any degree of reliability. As a result, a need still exists to develop methods for the successful treatment of colorectal carcinoma. Recently, the A33 antibody has been shown to be a promising reagent in the treatment against colorectal carcinoma. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Noninvasive detection of colorectal cancer and other gastrointestinal pathology Inventor(s): Nair, Padmanabhan P. (Ellicott City, MD) Correspondence: Mishrilal L. Jain; 11620 Masters Run; Ellicott City; MD; 21042; US Patent Application Number: 20010026923 Date filed: January 8, 2001
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Abstract: A method for isolating viable, biologically substantially pure exfoliated fecal colonocytes at normal ambient temperature is described. Immunocoprocytes and inflammatory cells indicative of certain gastrointestinal conditions and a noninvasive method for detecting colorectal cancer are set forth. Composition of transport and suspension media for isolation of colonocytes are detailed. Excerpt(s): The present invention is related to isolated colonocytes enabling early noninvasive detection of colorectal cancer and other gastrointestinal diseases. More particularly, the present invention is related to isolated, biologically substantially pure and viable immunocoprocytes and nonepithelial cells of lymphoid origin obtained from a small fecal sample. The invention is further related to providing a transport medium and a dispersion or suspension medium for isolating viable colonocytes from a fecal sample at normal ambient temperature and a method for detecting colorectal and other gastrointestinal pathology employing the isolated colonocytes of the present invention. The isolated colonocytes also allow the study and determination of other anomalous conditions, symptoms, disorders or pathological conditions.... A common gastrointestinal malignancy in humans is colorectal cancer. It has been estimated that colorectal cancer accounts for approximately 14% of all cancer-related deaths in men and women in the United States and its incidence continues to be high (Boring et al, CA Cancer J. Clin. 1994; 44:7-26). Early detection is a critical factor in successful treatment of this cancer, as it is in the treatment of other malignancies.... Screening approaches to detection of colon and colorectal tumors are presently based on the use of (a) fecal occult blood test (FOBT), (b) flexible sigmoidoscopy, (c) double contrast barium enema, and (d) colonoscopy. Among these screening tests only FOBT, which is based on a relatively high probability of bleeding from colorectal tumors, is noninvasive, simple and relatively inexpensive. However, frequent false positive and false negative results of the FOBT considerably limit its specificity and sensitivity. Other procedures are expensive and invasive. Hence, there is a clear need for providing a simple, noninvasive, reliable and inexpensive method for detecting colorectal cancer, gastrointestinal (GI) tract diseases and other pathological conditions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·
Noninvasive detection of colorectal cancer and other gastrointestinal pathology Inventor(s): Nair, Padmanabhan P. (Ellicott City, MD) Correspondence: Mishrilal L. Jain; 11620 Masters Run; Ellicott City; MD; 21042; US Patent Application Number: 20010026925 Date filed: January 8, 2001 Abstract: A method for isolating viable, biologically substantially pure exfoliated fecal colonocytes at normal ambient temperature is described. Immunocoprocytes and inflammatory cells indicative of certain gastrointestinal conditions and a noninvasive method for detecting colorectal cancer are set forth. Composition of transport and suspension media for isolation of colonocytes are detailed. Excerpt(s): The present invention is related to isolated colonocytes enabling early noninvasive detection of colorectal cancer and other gastrointestinal diseases. More particularly, the present invention is related to isolated, biologically substantially pure and viable immunocoprocytes and nonepithelial cells of lymphoid origin obtained from a small fecal sample. The invention is further related to providing a transport medium and a dispersion or suspension medium for isolating viable colonocytes from a fecal
Patents 399
sample at normal ambient temperature and a method for detecting colorectal and other gastrointestinal pathology employing the isolated colonocytes of the present invention. The isolated colonocytes also allow the study and determination of other anomalous conditions, symptoms, disorders or pathological conditions.... A common gastrointestinal malignancy in humans is colorectal cancer. It has been estimated that colorectal cancer accounts for approximately 14% of all cancer-related deaths in men and women in the United States and its incidence continues to be high (Boring et al, CA Cancer J. Clin. 1994; 44:7-26). Early detection is a critical factor in successful treatment of this cancer, as it is in the treatment of other malignancies.... Screening approaches to detection of colon and colorectal tumors are presently based on the use of (a) fecal occult blood test (FOBT), (b) flexible sigmoidoscopy, (c) double contrast barium enema, and (d) colonoscopy. Among these screening tests only FOBT, which is based on a relatively high probability of bleeding from colorectal tumors, is noninvasive, simple and relatively inexpensive. However, frequent false positive and false negative results of the FOBT considerably limit its specificity and sensitivity. Other procedures are expensive and invasive. Hence, there is a clear need for providing a simple, noninvasive, reliable and inexpensive method for detecting colorectal cancer, gastrointestinal (GI) tract diseases and other pathological conditions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·
Novel genes, compositions, kits, and methods for identification, assessment, prevention, and therapy of colon cancer Inventor(s): Burgart, Lawrence J. (Rochester, MN), Thibodeau, Stephen N. (Rochester, MN), Monahan, John E. (Walpole, MA), Schlegel, Robert; (Auburndale, MA), Guillemette, Tracy L. (Plaistow, NH), Berger, Allison; (Watertown, MA), Kamatkar, Shubhangi; (Newton, MA) Correspondence: Theodore R. Allen; Millennium Pharmaceuticals, Inc. 75 Sidney Street; Cambridge; MA; 02139; US Patent Application Number: 20030148410 Date filed: November 21, 2002 Abstract: The invention relates to newly discovered nucleic acid molecules and proteins associated with colon cancer. Compositions, kits, and methods for detecting, characterizing, preventing, and treating human colon cancers are provided. Excerpt(s): The present application claims priority from U.S. provisional patent application serial No. 60/339,971, filed on Dec. 10, 2001, and from U.S. provisional patent application serial No. 60/361,978, filed on Mar. 5, 2002. The present application also claims priority from U.S. provisional patent application serial No. 60/381,988, filed on May 20, 2002. All of the above applications are expressly incorporated by reference.... The field of the invention is colon cancer, including diagnosis, characterization, management, and therapy of colon cancer.... The increased number of cancer cases reported in the United States, and, indeed, around the world, is a major concern. Currently there are only a handful of detection and treatment methods available for specific types of cancer, and these provide no absolute guarantee of success. In order to be most effective, these treatments require not only an early detection of the malignancy, but also a reliable assessment of the severity of the malignancy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Novel methods of diagnosing colorectal cancer, compositions, and methods of screening for colorectal cancer modulators Inventor(s): Gish, Kurt C. (San Francisco, CA), Mack, David; (Menlo Park, CA), Wilson, Keith E. (Redwood City, CA) Correspondence: TOWNSEND AND TOWNSEND AND CREW, LLP; TWO EMBARCADERO CENTER; EIGHTH FLOOR; SAN FRANCISCO; CA; 94111-3834; US Patent Application Number: 20030108926 Date filed: October 3, 2002 Abstract: Described herein are methods that can be used for diagnosis and prognosis of colorectal cancer. Also described herein are methods that can be used to screen candidate bioactive agents for the ability to modulate colorectal cancer. Additionally, methods and molecular targets (genes and their products) for therapeutic intervention in colorectal and other cancers are described. Excerpt(s): The invention relates to the identification of expression profiles and the nucleic acids involved in colorectal cancer, and to the use of such expression profiles and nucleic acids in diagnosis and prognosis of colorectal cancer. The invention further relates to methods for identifying and using candidate agents and/or targets which modulate colorectal cancer.... Colorectal cancer is a significant cancer in Western populations. It develops as the result of a pathologic transformation of normal colon epithelium to an invasive cancer. There have been a number of recently characterized genetic alterations that have been implicated in colorectal cancer, including mutations in two classes of genes, tumor-suppressor genes and proto-oncogenes, with recent work suggesting that mutations in DNA repair genes may also be involved in tumorigenesis. For example, inactivating mutations of both alleles of the adenomatous polyposis coli (APC) gene, a tumor suppressor gene, appears to be one of the earliest events in colorectal cancer, and may even be the initiating event. Other genes implicated in colorectal cancer include the MCC gene, the p53 gene, the DCC (deleted in colorectal carcinoma) gene and other chromosome 18q genes, and genes in the TGF-.beta. signaling pathway. For a review, see Molecular Biology of Colorectal Cancer, pp238-299, in Curr. Probl. Cancer, September/October 1997.... Imaging of colorectal cancer for diagnosis has been problematic and limited. In addition, dissemination of tumor cells (metastases) to locoregional lymph nodes is an important prognostic factor; five year survival rates drop from 80 percent in patients with no lymph node metastases to 45 to 50 percent in those patients who do have lymph node metastases. A recent report showed that micrometastases can be detected from lymph nodes using reverse transcriptase-PCR methods based on the presence of mRNA for carcinoembryonic antigen, which has previously been shown to be present in the vast majority of colorectal cancers but not in normal tissues. Liefers et al., New England J. of Med. 339(4):223 (1998). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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NOVEL MUTATIONS IN HUMAN MLH1 AND HUMAN MSH2 GENES USEFUL IN DIAGNOSING COLORECTAL CANCER Inventor(s): LIN-GOERKE, JUILI LILLIAN; (SPRING CITY, PA), ROBBINS, DAVID; (STEVENSON RANCH, CA), LING, JESSICA C. (BENSALEM, PA) Correspondence: JANE MASSEY LICATA; 66 E MAIN STREET; MARLTON; NJ; 08053 Patent Application Number: 20010044936 Date filed: October 22, 1999 Abstract: Variant human MLH1 and MSH2 genes are provided. Methods of using these variant genes to diagnose hereditary non-polyposis colorectal cancer (HNPCC) and/or determine a patient's susceptibility to developing HNPCC are also provided. Methods and compositions for identifying new variant MLH1 of MSH2 genes are also provided. In addition, experimental models for hereditary non-polyposis colorectal cancer comprising these variant genes are provided. Excerpt(s): This application claims the benefit of U.S. provisional application Ser. No. 60/105,180, filed Oct. 22, 1998.... Colorectal cancer (CRC) is one of the most common fatal cancers in developed countries, and the worldwide incidence is increasing. The United States and the United Kingdom are high incidence countries, with an estimated 133,500 new cases and 55,300 deaths (Parker et al. CA Cancer J. Clin. 1996 46:5-27) in the United States and 30,941 cases and approximately 17,000 deaths in the United Kingdom (HMSO UK Cancer Registry Data). The population lifetime risk is 1 in 25 in the United States and Northern Europe and thus represents a significant public health issue (Sharp et al. Cancer Registration Statistics Scotland 1981-1990, Information and Statistics Division, The National Health Service in Scotland, Edinburgh (1993)). Identification of people who are predisposed to the disease would allow targeting of effective preventative measures with the aim of reducing the considerable cancer related mortality (Burke et al. J. Am. Med. Ass'n. 1997 227:915-919).... One group of people with a very high colorectal cancer risk are those who carry germline mutations in genes that participate in DNA mismatch repair. hMSH2 (Fishel et al. Cell 1993 75:1027-1038; Leach et al. Cell 1993 75:1215-1225; U.S. Pat. No. 5,591,826) and hMLH1 (Bronner et al. Nature 1994 368:258-261; Papadopoulos et al. Science 1994 263:1625-1629; PCT Publication No. WO 95/20678, published on Aug. 3, 1995) are the two genes most commonly involved in heredity predisposition to CRC, but mutations in hPMS1 and hPMS2 also occur in a minority of cases (Nicolaides et al. Nature 1994 371:75-80). Such mutations are usually associated with marked familial aggregation of colorectal, uterine and other cancers constituting the clinically defined autosomal dominant syndrome of hereditary nonpolyposis colorectal cancer (HNPCC) (Lynch et al. Gastroenterology 1993 104:1535-1549; Liu et al. Nature Med. 1996 2:169-174; Wijnen et al. Am. J. Hum. Genet. 1995 56:10601066; Mary et al. Hum. Mol. Genet. 1994 3:2067-2069; Nystrom-Lahti et al. Nature Med. 1995 1:1203-1206). However, an appreciable proportion of patients who have early onset colorectal cancer but who do not fulfill pragmatic criteria for HNPCC (Vasen et al. Dis. Colon Rectum 1991 34:424-425) also carry mismatch repair gene mutations (Liu et al. Nature Med. 1995 2:169-174; Dunlop et al. Br. Med. J. 1997 314:1779-1780). Thus, restricting genetic testing to individuals from families fulfilling HNPCC criteria is likely to exclude a significant fraction of gene carriers in the general population. However, screening unselected patients with sporadic cancer represents an enormous workload and may provide a very low yield of mutation carriers (Liu et al. Nat. Med. 1995 1:348352; Tomlinson et al. J. Med. Genet. 1997 34:39-42). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Nutritious supplemental composition for suppression against onset of large intestinal cancer and manufacturing method thereof Inventor(s): Iwasaki, Teruaki; (Sapporo-shi, JP) Correspondence: MCKEE, VOORHEES & SEASE, P.L.C. 801 GRAND AVENUE; SUITE 3200; DES MOINES; IA; 50309-2721; US Patent Application Number: 20030157127 Date filed: February 19, 2003 Abstract: In view of an acknowledgement that keeping a healthy body is a fundamental matter for overcoming cancer, it is an object of the present invention to provide composition containing well-balanced nutrition, having an effect to suppress the mutagenesis substances, having no sub-action even if the composition is continued to be taken as nutritious supplemental substance and capable of promoting healthy state. There are provided a nutritious supplemental composition for suppression against large intestinal cancer and its manufacturing method in which dietary fiber in a range of 15 wt % to 30 wt % in respect to a total amount of composition is contained in the dried koji fine powder including dead fungi of Aspergillus while keeping a capability of catalysis of groups of enzyme produced by Aspergillus. Excerpt(s): This invention relates to a nutritious supplemental composition for suppression against onset of large intestinal cancer in which it shows a superior suppression against onset of large intestinal cancer.... In particular, in the present invention, rice bran is heated with steam, Aspergillus, Aspergillus oryzae strain, for example, is mixed with the rice bran, they are cultivated and ripened to make rice bran koji, Aspergillus is annihilated, and the enzyme groups produced by Aspergillus are changed into the dried koji fine powder of dried powder under a state in which a proper capability of catalysis of enzyme itself is not lost.... Either dietary fiber aiming at removal of mutagen or plant protein acting as nutritious element is contained in it and the present invention relates to the nutritious supplemental composition for suppression against onset of large intestinal cancer and its manufacturing method. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Polynucleotides related to colon cancer Inventor(s): Kang, Sanmao; (Richmond, CA), Reinhard, Christoph; (Alameda, CA), Kennedy, Giulia; (San Francisco, CA), Jefferson, Anne Bennett; (Oakland, CA) Correspondence: Chiron Corporation; Intellectual Property - R440; P.O. BOX 8097; Emeryville; CA; 94662-8097; US Patent Application Number: 20030008284 Date filed: June 15, 2001 Abstract: The present invention is based on the discovery of polynucleotides that represent genes that are differentially expressed in colon cancer, e.g., adenomatous polyp, colorectal carcinoma, high metastatic potential colon tumor and metastatic colon cancer. The invention features methods of identifying cells affected by such colon diseases by detection of a gene product encoded by such differentially expressed genes, as well as method of modulating expression of such gene products to effect therapy
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(e.g., to decrease growth and/or affect abnormal characteristics of cancerous or dysplastic colon cells). Excerpt(s): This application claims the benefit of U.S. provisional application serial No. 60/211,835, filed Jun. 15, 2000, which application is hereby incorporated by reference.... The present invention relates to genes differentially expressed in colon cancer and dysplasia. More specifically, it relates to polynucleotides that are differentially regulated in colon cancer and the encoded gene products.... Colon cancer is the second leading cause of cancer-related deaths in the United States. The American Cancer Society estimates that there will be approximately 94,700 new cases of colon cancer in the United States in 1999, and that colon cancer will be responsible for about 47,900 deaths. The colon has four sections: the ascending colon, the transverse colon, the descending colon and the sigmoid colon, and terminates with the rectum. Adenomatous polyps or adenomas, common benign lesions that progress to carcinomas can develop in any of the four sections of the colon or in the rectum. Over 95% of colon cancers are adenocarcinomas, or cancers of the cells that line the inside of the colon. Colon cancer frequently metastasizes to the liver and the lung. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html ·
Preventative and treatment effects of morinda citrifolia as a colon cancer cell growth inhibitor Inventor(s): Su, Chen; (West Jordan, UT), Jensen, Summer; (Cedar Hills, UT), Story, Stephen P. (Alpine, UT), Palu, Afa Kehaati; (Orem, UT), Jensen, Claude Jarakae; (Cedar Hills, UT) Correspondence: Kirton & McConkie; 1800 Eagle Gate Tower; 60 East South Temple; Salt Lake City; UT; 84111; US Patent Application Number: 20030134001 Date filed: October 31, 2002 Abstract: The present invention features methods and formulations or compositions for the treatment of colon cancer, and particularly for the inhibition, prevention and/or reduction of cancerous cell growth, as well as the destruction of early stage cancerous cells within the colon region of a mammal, wherein the formulations and compositions comprise an identified amount or concentration of a processed Morinda citrifolia product or an active ingredient there from, as obtained from the Indian Mulberry plant. Excerpt(s): This application claims priority to U.S. Provisional Application Serial No. 60/335,346, filed Nov. 2, 2001, entitled, "Morinda citrifolia Enhanced Colon Cancer Cell Growth Inhibitor".... The present invention relates to in vivo cell growth inhibitors, and more particularly to an in vivo cancer cell growth inhibitor formulated to inhibit colon cancer cell growth in mammals. Specifically, the present invention relates to an in vivo colon cancer cell growth inhibitor or naturaceutical composition formulated with Morinda Citrifolia from the Indian Mulberry plant.... Cancer of the colon is a deadly form of cancer affecting millions of people. Research is ongoing in the fight against cancer, with hopes of one day finding a complete cure for this ugly disease. Until a complete cure is found, researchers, medical professionals, and several interested groups are furthering efforts to treat those currently suffering from the disease. As such, information and treatment possibilities are continuously being updated. The following represents the most current and up-to-date information pertaining to cancer of the colon.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with colon cancer, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “colon cancer” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on colon cancer. You can also use this procedure to view pending patent applications concerning colon cancer. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 7. BOOKS ON COLON CANCER Overview This chapter provides bibliographic book references relating to colon cancer. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on colon cancer include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “colon cancer” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on colon cancer: ·
Cancer Screening Source: St. Louis, MO, Mosby-Year Book, Inc., 307 p., 1996. Contact: Mosby-Year Book, Inc., 11830 Westline Industrial Drive, St. Louis, MO 63146. Summary: Cancer Screening is a monograph that includes articles written by experts in the field of cancer screening, who present current information and bring attention to controversial issues surrounding cancer screening. The monograph is divided into two main sections preceded by a chapter titled Principles of Cancer Screening, which defines key terms associated with screening and describes measures of validity for a screening test, major principles of cancer screening, and evaluation of a proposed screening strategy. Part I, Screening for Specific Cancers, contains chapters on (1) breast cancer as an appropriate illness for screening, mammography as an appropriate screening test, case-control studies and randomized controlled trials, demonstration and implementation projects, and nationwide dissemination programs and policy
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recommendations; (2) cervical cancer epidemiology, pathogenesis, screening, prevention of invasive cervical cancer, and future directions; (3) colon and rectal cancer etiology and prevention, screening procedures, and practice and research recommendations; (4) the prostate cancer screening debate, prostate specific antigen (PSA) screening studies, and recommendations about screening for prostate cancer; (5) lung cancer presentation, staging, treatment outcome, epidemiology, biology, genetic changes, historical screening studies, tumor markers, identification of high-risk groups, and prospects for screening approaches; (6) ovarian cancer epidemiology, efficacy of screening, genetics, molecular biology and ovarian cancer screening, and primary care guidelines; (7) skin cancer and melanoma epidemiology, definitions, screening efficacy, education, prevention and early detection activities in Europe, primary prevention, screening program pitfalls, identification of high-risk populations, skin screening, molecular biology and skin screening, guidelines for primary care, financial health policy, and outlook for the future; and (8) miscellaneous tumors associated with other cancers. Part II, General Considerations in Cancer Screening, contains chapters on (1) molecular screening and the prevention of colon cancer, (2) breast cancer genetics, (3) adherence to cancer screening, (4) issues in developing a cancer screening program, and (5) legislative efforts to fund cancer screening. ·
Cancer Control Makes Sense Source: Austin, TX, Texas Department of Health, Chronic Disease Prevention Program, 43 p., 1989. Contact: Texas Department of Health, Chronic Disease Prevention Program, 1100 West 49th Street, Austin, TX 78756. (512) 458-7534. Summary: Cancer Control Makes Sense, a booklet addressing cancer problems in Texas, was developed by the Texas Department of Health. Statistics, graphs, charts, and maps illustrate cancer prevalence in Texas. The booklet addresses lung cancer, breast cancer, cervical cancer, and colon cancer. Discussion of each cancer includes ethnic and regional variations and risk factors. The booklet provides recommended actions to reduce cancer rates.
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Don't Die of Embarrassment: Life After Colostomy and Other Adventures Source: New York, NY: Simon and Schuster. 1997. 256 p. Contact: Available from Simon and Schuster. Mail Order, 100 Front Street, Riverside, NJ 08075. (800) 331-6531. E-mail:
[email protected]. Website: www.simonsays.com. PRICE: $12.00 plus shipping and handling. ISBN: 0684846241. Summary: When the successful actress Barbara Barrie received a diagnosis of colorectal cancer in 1993, she knew that this was the greatest crisis she and her family would face. But it also became an adventure that, through courage and humor, brought new joys and a greater appreciation to her life. More than just a memoir, this book provides valuable information about the ostomy experience. Throughout the book, Barrie gives essential information about the occurrence of colon cancer, its symptoms, and treatment options, and guidelines for people learning to adjust to an altered lifestyle after surgery. The book is written in a conversational, story style, with Barrie sharing her thoughts and fears. The book includes an afterword, written by Dr. Otis W. Brawley, that offers some practical information about diagnosis, screening, warning signs, prevention, and treatment of colon cancer. The book concludes with a chapter describing additional sources of information, and a subject index.
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Our Health, Our Lives: A Revolutionary Approach to Total Health Care for Women Source: New York, NY: Pocket Books. 1995. 448 p. Contact: Available from Pocket Books. 1230 Sixth Avenue, New York, NY 10020. (800) 223-2336. PRICE: $24. ISBN: 0671880853. Summary: In this book, the author demonstrates how medicine can function to serve women's needs and shows women how to help start that process in their own lives. Eighteen chapters are presented in four sections: the woman-centered approach; total health in context; women's life cycles; and mind and body together. Topics include becoming one's own health advocation; how the female body works; risk factors for heart disease; women's cancer; diabetes; preventing osteoporosis; bladder conditions; fatigue and the immune system; the patterns in women's lives; pregnancy and beyond; the menopause years; the emotionally healthy woman; healthy sexuality; eating problems; and substance addictions. Specific topics that address digestive diseases include risk factors for colon cancer; nutrition, including fats and fiber; eating disorders; appendicitis; cholesterol; dietary calcium; depression and the immune system; dieting and weight loss; eating habits; gallbladder disease; pregnancy and the gastrointestinal system; systemic lupus erythematosus; obesity; and vitamins. A detailed subject index concludes the book.
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Contemporary Diagnosis and Management of Ulcerative Colitis and Proctitis Source: Newtown, PA: Handbooks in Health Care. 1995. 173 p. Contact: Available from Handbooks in Health Care. 9 Pheasant Run, Newtown, PA 18940. (215) 860-9600. PRICE: $9.95 plus $2 shipping (as of 1995). ISBN: 1884065082. Summary: In this handbook, the author provides readers with a detailed overview of the diagnosis and management of ulcerative colitis and proctitis. Fourteen chapters cover epidemiology; etiology, pathogenesis, and pathophysiology; clinical presentation, diagnostic evaluation, and differential diagnosis; commonly used drugs for ulcerative colitis and ulcerative proctitis; potential new drugs and novel therapeutic approaches; the management of ulcerative proctitis; the management of distal ulcerative colitis, leftsided ulcerative colitis, and mild to moderate pancolitis; the management of fulminant ulcerative colitis and toxic megacolon; surgical management; associated extraintestinal disorders; colon cancer surveillance; pregnancy and nursing; the pediatric patient and the elderly patient; and psychosocial and quality of life issues. Each chapter includes figures and tables where appropriate, and brief references; a subject index concludes the handbook.
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Angry Gut: Coping with Colitis and Crohn's Disease Source: New York, NY: Plenum Press. 1993. 350 p. Contact: Available from Plenum Publishing. 233 Spring Street, New York, NY 100131578. (800) 221-9369 or (212) 620-8000. Fax (212) 647-1898. E-mail:
[email protected]. PRICE: $26.95. ISBN: 0306444704. Summary: This book is intended for patients with inflammatory bowel disease (IBD), their families, and the nurses, primary care physicians, and other health professionals who work with these patients. Twenty-seven chapters are presented in five parts: understanding the anatomy and physiology of IBD; ulcerative colitis; Crohn's disease; special topics related to IBD; and treatments and investigations. Specific topics related to IBD include history; epidemiology; symptoms; diagnosis; treatment;and complications;
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variant colitis; extraintestinal manifestations; colon cancer; psychological factors and quality of life issues; sex and reproduction; nutrition; drug therapy, including 5-ASA, steroids, immunosuppressives, and antibiotics; surgery; and research. The volume includes some technical language and emphasizes a cooperative, team approach between patient and physician. A subject index is included.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in PrintÒ). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “colon cancer” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “colon cancer” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “colon cancer” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): ·
21st Century Complete Medical Guide to Colon Cancer (Colorectal, Rectal and Anal Cancer) - Authoritative Government Documents and Clinical References for Patients and Physicians with Practical Information on Diagnosis and Treatment Options by PM Medical Health News; ISBN: 1592480020; http://www.amazon.com/exec/obidos/ASIN/1592480020/icongroupinterna
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50 Ways to Prevent Colon Cancer by M. Sara Rosenthal; ISBN: 0737304596; http://www.amazon.com/exec/obidos/ASIN/0737304596/icongroupinterna
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Advancements in Colon Cancer Therapeutics [DOWNLOAD: PDF] by BioSeeker Group AB (Author); ISBN: B00008IA0M; http://www.amazon.com/exec/obidos/ASIN/B00008IA0M/icongroupinterna
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Calcium, Vitamin D, and Prevention of Colon Cancer by Martin S. Newmark, et al; ISBN: 0849342643; http://www.amazon.com/exec/obidos/ASIN/0849342643/icongroupinterna
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Cell and Molecular Biology of Colon Cancer by Leonard H. Augenlicht (Editor) (1989); ISBN: 0849347106; http://www.amazon.com/exec/obidos/ASIN/0849347106/icongroupinterna
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Colon Cancer by Stephen Fisher, David Fischer (Illustrator); ISBN: 1555610749; http://www.amazon.com/exec/obidos/ASIN/1555610749/icongroupinterna
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Colon Cancer & the Polyps Connection by Stephen Fisher, et al (1995); ISBN: 1555610803; http://www.amazon.com/exec/obidos/ASIN/1555610803/icongroupinterna
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Colon Cancer Cells (Cell Biology: A Series of Monographs) by Mary Pat Moyer, George H. Poste; ISBN: 0125093756; http://www.amazon.com/exec/obidos/ASIN/0125093756/icongroupinterna
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Colon Cancer Genetics by Patrick Lynch, Henry Lynch (Editor); ISBN: 0442249187; http://www.amazon.com/exec/obidos/ASIN/0442249187/icongroupinterna
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Colon Cancer Prevention: Dietary Modulation of Cellular and Molecular Mechanisms (Advances in Experimental Medicine and Biology, 470) by American Institute for
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Cancer Research (Editor), Rachel S. Abroms; ISBN: 0306462079; http://www.amazon.com/exec/obidos/ASIN/0306462079/icongroupinterna ·
Colon Cancer: Greater Use of Screenings Would Save Lives: Hearing Before the Special Committee on Aging, U.S. Senate by Charles E. Grassley (2000); ISBN: 0756715733; http://www.amazon.com/exec/obidos/ASIN/0756715733/icongroupinterna
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Diagnostic Assays for Colon Cancer by Abulkalam M. Shamsuddin (1991); ISBN: 0849365406; http://www.amazon.com/exec/obidos/ASIN/0849365406/icongroupinterna
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Gut- Check: Your Prime Source for Bowel Health and Colon Cancer Prevention by Jeffrey M. Aron, Harriette E. Aron (2001); ISBN: 0759604983; http://www.amazon.com/exec/obidos/ASIN/0759604983/icongroupinterna
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Health Benefits of Probiotics (Latest Research Showing Benefits for Digestion, Cholesterol, Yeast Infection, Immune System, Colon Cancer, Ulcers, etc) by Beth LeyJacobs (2000); ISBN: 1890766100; http://www.amazon.com/exec/obidos/ASIN/1890766100/icongroupinterna
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Tell Me What to Eat to Help Prevent Colon Cancer by Elaine Magee; ISBN: 156414514X; http://www.amazon.com/exec/obidos/ASIN/156414514X/icongroupinterna
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The Official Patient's Sourcebook on Colon Cancer: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597833508; http://www.amazon.com/exec/obidos/ASIN/0597833508/icongroupinterna
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Understanding Colon Cancer by A. Richard, M.D., F.A.C.P. Adrouny; ISBN: 1578064732; http://www.amazon.com/exec/obidos/ASIN/1578064732/icongroupinterna
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What To Do If You Get Colon Cancer : A Specialist Helps You Take Charge and Make Informed Choices by Paul Miskovitz (Author), Marian Betancourt (Author) (1997); ISBN: 0471159840; http://www.amazon.com/exec/obidos/ASIN/0471159840/icongroupinterna
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Why Die of Colon Cancer? by Francis G., M.D. Mackey, Francisa Mackey; ISBN: 1582441278; http://www.amazon.com/exec/obidos/ASIN/1582441278/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “colon cancer” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 11 In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found.
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Atlas of selective sentinel lymphadenectomy for melanoma, breast cancer, and colon cancer Author: Leong, Stanley P. L.; Year: 2002; Boston: Kluwer Academic Publishers, c2002; ISBN: 1402070136 http://www.amazon.com/exec/obidos/ASIN/1402070136/icongroupinterna
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Colon cancer Author: Grundmann, E. (Ekkehard); Year: 1978; Stuttgart; New York: Fischer, 1978; ISBN: 3437105604
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Colon cancer: a report by 32 Illinois hospitals on 910 cases diagnosed in 1968. Author: American Cancer Society. Illinois Division.; Year: 1976; Chicago: American
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Colon cancer study: May 1991. Author: Physician Insurers Association of America.; Year: 1991; [Rockville, Md.?]: Physician Insurers Association of America, c1991
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Hereditary breast, ovarian, and colon cancer: proceedings of a workshop held at the Sheraton Washington Hotel, Washington, D.C., April 27-29, 1994 Author: Giusti, Ruthann M.; Year: 1995; Bethesda, MD: National
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Hyperthermia plus chemotherapy for colon cancer Author: ECRI (Organization). Health Technology Assessment Information Service.; Year: 2001; Plymouth Meeting, PA: ECRI, c2001
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Trial of two decision aids for colon cancer screening: abstract, executive summary, and final report Author: Dolan, James G.; Year: 2000; Rockville, Md.: Agency for Healthcare Research and Quality, Center for Research Dissemination and Liaison, 2000
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Understanding colon cancer Author: Adrouny, A. Richard,; Year: 2002; Jackson: University Press of Mississippi, c2002; ISBN: 1578064724 http://www.amazon.com/exec/obidos/ASIN/1578064724/icongroupinterna
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Update gastroenterology 2000: Barrett's esophagus, colon cancer, and tumor imaging: Postgraduate Course 2000, Brussels, November 25 Author: European Association for Gastroenterology and Endoscopy. Postgraduate Course; Year: 2000; Montrouge, France: John Libbey Eurotext, c2000; ISBN: 2742003460
Chapters on Colon Cancer In order to find chapters that specifically relate to colon cancer, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and colon cancer using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “colon cancer” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on colon cancer: ·
Gastrointestinal Problems Including Colon Cancer Source: in Rosenfeld, J.A., ed. Women's Health in Primary Care. Baltimore, MD: Williams and Wilkins. 1997. p. 633-660. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-8555. Fax (800) 447-8438. PRICE: $59.95 (paperback). ISBN: 0683073664.
Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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Summary: This chapter, from a book on women's health for primary care providers, reviews gastrointestinal problems in women. The chapter covers diseases of the upper GI tract, including gastroesophageal reflux disease (GERD), peptic ulcer disease, and gastric carcinoma; gallstones; liver diseases, including primary biliary cirrhosis, autoimmune liver disease, drug-induced liver disease, and alcoholic liver disease; and lower GI disease, including irritable bowel syndrome, inflammatory bowel disease, and colon cancer. For each disease, the author discusses incidence, risk factors, clinical symptoms, diagnosis, and treatment options. 1 figure. 8 tables. 90 references. ·
Colorectal Cancer Source: in Cancer Screening: Theory and Practice. Kramer, B.S. Gohagan, J.K. Prorok, P.C. eds. Marcel Dekker, Inc., New York, NY, pp. 219-265, 1999. Contact: Marcel Dekker, Inc., 270 Madison Avenue, New York, NY 10016. (212) 6969000. FAX: (212) 685-4540. INTERNET: http://www.dekker.com. Summary: Colorectal Cancer, a chapter in Cancer Screening: Theory and Practice, focuses on issues related to colorectal cancer screening. Colorectal cancer is the fourth most common nonskin cancer worldwide. Survival is dependent on the stage at which the cancer is detected. Lifestyle is a major determinant of colorectal cancer risk. Risk factors include (1) dietary animal fat and dairy products, (2) alcohol, (3) physical inactivity, (4) overweight, (5) not having given birth, (6) history of ulcerative colitis, and (7) family history. There is strong evidence that colon cancer develops from preexisting adenomas. A number of genes have been associated with colorectal cancer. Screening tests for colorectal cancer include (1) digital rectal examination (DRE), (2) fecal occult blood testing (FOBT), (3) sigmoidoscopy, (4) barium enema, (5) colonoscopy, and (6) genetic testing. Studies on the effectiveness of DRE have yielded inconclusive results. A major concern about FOBT is the lack of sensitivity, but mortality and followup studies on the effectiveness of FOBT have shown a 33 percent reduction in the mortality rate in those screened annually. Randomized trials and observational studies have shown the effectiveness of sigmoidoscopy. The main complication of endoscopic colorectal screening is bowel perforation. The risks are much greater for colonoscopy than for sigmoidoscopy. Endoscopic procedures are uncomfortable, and colonoscopy usually requires sedation. Models for assessing the cost-effectiveness of colorectal cancer screening are limited by a lack of knowledge about the efficiency of the tests, the appropriate interval between tests, and the appropriate age for starting and stopping screening. A comprehensive public education program is necessary to break down social taboos about bowel cancer. Screening recommendations from professional organizations are complex and overlapping, but for average-risk persons age 50, recommendations are (1) annual FOBT, (2) flexible sigmoidoscopy every 5 years, (3) double-contrast barium enema every 5 to 10 years, and (4) colonoscopy every 10 years.
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Advances in Screening for Colorectal Cancer Source: in Advances in Cancer Screening. Miller, A.B. ed. Boston, MA. Kluwer Academic Publishers, pp. 51-76, 1996. Contact: Kluwer Academic Publishers, 101 Philip Drive, Assinippi Park, Norwell, MA 02061. Summary: Advances in Screening for Colorectal Cancer, a chapter in Advances in Cancer Screening, provides an overview of the scientific evidence on screening for colorectal cancer. Primary prevention of colorectal cancer remains speculative because there are few established etiologic factors. Secondary prevention through annual fecal
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occult blood testing (FOBT) has been shown to reduce colorectal cancer mortality. There have been four randomized controlled trials of FOBT's. The Minnesota trial is the only study to date that has published a mortality reduction. Through 13 years of followup, the Minnesota study showed a 33 percent mortality reduction. Preliminary results from a Danish trial have shown a 20 percent reduction. There are two prospective, nonrandomized controlled FOBT trials. One study, in New York City, New York, showed a 43 percent reduction and improved survival. Results from a study in France are pending. Results from case-control studies ranged from no mortality reduction to 57 percent reduction. Three types of FOBT's are (1) immunochemical, (2) hemeporphyrin, and (3) guaiac. Immunochemical tests detect only hemoglobin and globin, and are not affected by diet. Hemeporphyrin tests detect the broadest range of blood derivatives. Guaiac tests, such as Hemoccult, detect heme in any form. Screening with flexible sigmoidoscopy to detect adenomatous polyps has received considerable attention. The rationale for this test is that most cancers arise from polyps. The advantage of flexible sigmoidoscopy is direct visualization of adenomas. The disadvantage is that it is only useful for examining the distal portion of the colon. Colonoscopy has been suggested as a one-time screen during the sixth decade of life. The only test that has proven to be effective in reducing colorectal cancer mortality is Hemoccult conducted annually after age 50. ·
Colorectal Cancer Screening in a Defined Population Source: in Advances in Cancer Control: Cancer Control Research and the Emergence of the Oncology Product Line. Engstrom, P.F. Anderson, P.N. Mortenson, L.E. eds. New York, NY, Alan R. Liss, Inc., pp. 7-19, 1988. Contact: Alan R. Liss, Inc., 41 East 11th Street, New York, NY 10003. Summary: Colorectal Cancer Screening in a Defined Population, a chapter in Advances in Cancer Control: Cancer Control Research and the Emergence of the Oncology Product Line, focuses on a joint venture for the delivery of cancer-related medical care called US HEALTHCHECK. Developed in 1985, this collaboration resulted in the development of a breast and colorectal cancer screening and early detection program for members of a health maintenance organization (HMO) for Pennsylvania and New Jersey. The US HEALTHCHECK colorectal cancer screening program was intended to reduce morbidity and mortality from colorectal cancer among eligible HMO members by (1) detecting early stage cancer through fecal occult blood testing, (2) ensuring the provision of state-of-the-art care and treatment to target populations with positive findings, and (3) utilizing the expertise of a comprehensive cancer center to evaluate patterns of colon and rectum cancer patient management. These goals were to be achieved by integrating the US HEALTHCHECK program into an Individual Practice Association (IPA). The authors present details on participation in colorectal cancer screening programs and discuss the integration of colorectal cancer screening into primary physician practice. They explain the structure of the US HEALTHCHECK colorectal cancer screening program. The organizational structure of the IPA/HMO setting renders this model of physician practice an ideal setting for initiating Phase IV cancer control studies. The similarity of the IPA/HMO physician practice settings to those of solo and group fee-for-service practitioners suggests generalizability of programmatic methods and related clinical outcomes to non-HMO medical care delivery systems. Several aspects of the US HEALTHCHECK program are currently being evaluated, Including (1) population member initial participation, (2) member adherence, and (3) physician management and diagnosis of patients.
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Prevention and Control of Colorectal Cancer Source: in Cancer Prevention and Control. Greenwald, P. Kramer, B.S. Weed, D.L. eds. New York, NY, Marcel Dekker, Inc., pp. 537-559, 1995. Contact: Marcel Dekker, Inc., 270 Madison Avenue, New York, NY 10016. Summary: Prevention and Control of Colorectal Cancer, a chapter in Cancer Prevention and Control, discusses the role played by primary and secondary prevention in the control of colorectal cancer. Primary prevention involves the identification and avoidance of environmental factors related to carcinogenesis. Secondary prevention includes the identification and eradication of premalignant lesions and the early detection and treatment of cancer. The evidence that nutritional factors can promote or inhibit the development of colorectal cancer suggests that primary prevention may play an important part in the control of this disease. Researchers review the data from the United States and abroad on the relationship between colorectal cancer and colorectal adenomas and (1) dietary fat consumption; (2) fiber intake; (3) excessive caloric intake and body weight; and (4) intake of minerals, vitamins, and trace elements. Researchers conclude this section by discussing gene-nutrient interaction in colon carcinogenesis and dietary guidelines for the prevention of colon cancer. Researchers state that definitive evidence of the relationship between diet and cancer must await the results of prospective, randomized intervention studies in humans. The discussion of secondary prevention focuses on screening for average- and high-risk patients. Average- or standard-risk patients are at risk by virtue of age only and have no other associated risk factors. High-risk patients have conditions from which colorectal cancers are suspected to arise, including adenomatous polyps, familial syndromes, sporadic cancer, genetic abnormalities, and ulcerative colitis. The chapter details screening and followup guidelines for both sets of at-risk patients. Researchers suggest that primary prevention targeted to the general population may reduce the incidence of adenomas and thus reduce future colorectal cancer incidence and mortality. Secondary prevention strategies may help the general population over age 50, by detecting earlier-stage cancers or extirpating adenomas. Researchers also discuss their hopes for more sophisticated screening techniques and easily-implemented nutritional interventions.
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Screening for Colorectal Cancer: State of the Art on Screening for Colorectal Cancer Source: in Cancer Screening. Miller, A.B. Chamberlain, J. Day, N.E. Hakama, M. Prorok, P.C. eds. Cambridge, England, Cambridge University Press, pp. 81-138, 1991. Contact: Press Syndicate of the University of Cambridge, 40 West 20th Street, New York, NY 10011-4211. Summary: Screening for Colorectal Cancer: State of the Art on Screening for Colorectal Cancer, a section in Cancer Screening, reviews methods, trials, and studies associated with detection of colorectal cancer. The chapters in this section are: (1) Colon Cancer Control Study: Status and Current Issues; (2) An Update on the Nottingham Trial of Fecal Occult Blood Screening for Colorectal Carcinoma; (3) A Randomized Trial of Fecal Occult Blood Testing for Early Detection of Colorectal Cancer, Results of Screening and Rescreening of 51,325 Subjects; (4) Interim Report on a Randomized Trial of Screening for Colorectal Cancer with Hemoccult-II; (5) Case-control Evaluation of Colorectal Cancer Screening in the Federal Republic of Germany; and (6) Summary of the Discussion on Colorectal Cancer Screening. While the current trials will eventually reveal the effect of screening for occult blood in the stool on colorectal cancer mortality, no single trial will be definitive and most will require more time. Several more years of followup will also be required before the effect of adenoma removal on cancer incidence
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is determined. Meanwhile, screening for colorectal cancer or its precursors is not a justifiable public health policy.
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CHAPTER 8. MULTIMEDIA ON COLON CANCER Overview In this chapter, we show you how to keep current on multimedia sources of information on colon cancer. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Video Recordings An excellent source of multimedia information on colon cancer is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “colon cancer” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “colon cancer” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on colon cancer: ·
Gastroenterology for the Primary Care Physician Source: Mount Laurel, NJ: CME Conference Video, Inc. 1994. (instructional package). Contact: Available from CME Conference Video, Inc. 2000 Crawford Place, Suite 100, Mount Laurel, NJ 08054. (800) 284-8433. Fax (800) 284-5964. PRICE: $450 plus $12.25 shipping and handling (as of 1995); group practice package available. Program No. 153. Summary: This continuing education course is designed to update internists, family practitioners, and other primary care physicians on new developments in gastroenterology. The format of the course focuses on case presentations emphasizing important and evolving concepts in gastroenterology. The emphasis is on practical diagnostic and therapeutic choices and the development of cost effective management algorithms. Topics include hepatitis C, non-cardiac chest pain, psychopharmacologic approaches to acid reduction, peptic ulcer disease, Helicobacter pylori, risk factors for NSAID injury, Clostridium difficile, travelers' diarrhea, constipation in the elderly, pancreatitis, endoscopic ultrasound, gastroesophageal reflux disease, Barrett's
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esophagus, liver disease, GI manifestations in AIDS, esophagitis, fecal incontinence, diagnostic testing, irritable bowel syndrome, inflammatory bowel disease, drug therapy, chronic diarrhea, gallstone disease, colon cancer, cirrhosis, and ascites. The program offers 11 hours of AMA-PRA Category 1 credit. (AA-M). ·
Ostomy Care Source: Toronto, Ontario: Medical Audio Visual Communications, Inc. 1993. (videocassette). Contact: Available from Medical Audio Visual Communications, Inc. P.O. Box 84548, 2336 Bloor Street West, Toronto, Ontario M6S 1TO Canada. (800) 757-4868 or (905) 6021160. Fax (905) 602-8720. E-mail:
[email protected]. PRICE: $249.00 plus shipping and handling. Order number: MED052. Summary: This program is designed to train nurses aides or nursing assistants in the care of patients who have an ostomy. The program features two different patients, a young woman who undergoes an ileostomy for chronic ulcerative colitis and an older man who undergoes a sigmoid colostomy for colon cancer. The program first reviews the different types of ostomies, the reasons why a patient might need to have a temporary or permanent ostomy, and the different types of stomas that can be created (loop, double-barrel, and end stomas). The program then discusses the importance of the physician, enterostomal (ET) nurse, and patient working together to determine the type and placement of the stoma required and to develop the patient care plan. Peristomal skin care is always vital, regardless of the type of stoma. The program emphasizes that preoperative care and patient education will greatly increase the likelihood of success. The program then reviews the use of pouch appliances, the types of pouches (and indications for each), the use of pouch deodorant, and the need to resize the appliances as the stoma changes (this can take 6 to 8 weeks). The ET nurse is then shown changing the woman's ileostomy pouch in the hospital: gathering supplies (each is displayed), measuring the stoma, using skin barrier paste, placing the skin barrier, placing the pouch, and documenting the appearance of stoma and skin, the pouch contents, and the presence of flatus (gas). The program then shows a different home health care ET nurse helping the man with the colostomy irrigate his stoma. Again, the stoma supplies and the irrigation process are outlined and depicted. Two final sections of the video discuss the dietary restrictions that may be indicated for the ileostomy and for the colostomy and the problems that patients may encounter for which a health care provider needs to be contacted.
Bibliography: Multimedia on Colon Cancer The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in colon cancer (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on colon: ·
A pelvic evisceration for sigmoid colon cancer [videorecording]: preserving the lower part of the rectum with excision of the bilateral internal iliac arteries and veins. Year: 1986; Format: Videorecording; Danbury, Conn.: Davis+Geck, distributors, 1986
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Alzheimer's disease [videorecording]: capturing precious moments; Trauma to triumph: coping with colon cancer experience Source: HSTN; Year: 2002; Format: Videorecording; Carrollton, TX: HSTN, c2002
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Can the GI prevent cancer? [sound recording]: colon cancer & Barrett's esophagus: recorded at DDW 1995 in San Diego Source: AGA, American Gastroenterological Association; Year: 1995; Format: Sound recording; [Bethesda, Md.]: The Association, [1995?]
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Clinical aspects of genetic testing in colon cancer and GI disease [sound recording]: recorded at DDW 1995 in San Diego Source: AGA, American Gastroenterological Association; Year: 1995; Format: Sound recording; [Bethesda, Md.]: The Association, [1995?]
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Colon cancer [sound recording] Source: American College of Surgeons; Year: 1991; Format: Sound recording; [Chicago, Ill.]: The College, [1991]
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Colon cancer [sound recording] Source: [Bert Vogelstein]; Year: 1996; Format: Sound recording; [Bethesda, Md.: National Institutes of Health, 1996]
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Colorectal cancer [videorecording] Source: a presentation of Films for the Humanities & Sciences; Year: 1993; Format: Videorecording; Princeton, N.J.: Films for the Humanities and Sciences, c1993
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Detection of asymptomatic colon cancer [videorecording] Source: School of Medicine, University of North Carolina; Year: 1973; Format: Videorecording; Chapel Hill: The University, [1973]
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Diet and colon cancer [slide] Source: sponsored by Department of Biochemistry, School of Medicine, State University of New York at Buffalo; Year: 1979; Format: Slide; [Buffalo, N.Y.]: The Department, 1979
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Inherited colon cancer genes [sound recording]: recorded at DDW 1994 in New Orleans Source: AGA; Year: 1994; Format: Sound recording; [Bethesda, Md.]: American Gastroenterology Association, [1994?]
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Local excision of colon cancer [videorecording] Source: from the Film Library and the Clinical Congress of ACS; Year: 1995; Format: Videorecording; Boston, Mass.: Deaconess Hospital, c1995
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Mutations in colon cancer [sound recording]: mechanisms and causes: recorded at DDW 1995 in San Diego Source: AGA; Year: 1995; Format: Sound recording; [Bethesda, Md.]: American Gastroenterological Association, [1995?]
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Nursing management of the patient with colon cancer [videorecording] Source: [presented by] Mosby; Samuel Merritt College, Studio Three Productions; Year: 1995; Format: Videorecording; [St. Louis, Mo.]: Mosby-Year Book, c1995
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Oncology update [videorecording]: colon cancer Source: a co-production of the Regional Audio Visual Center and Physician Education & Development; Year: 1995; Format: Videorecording; [Oakland, Calif.]: Kaiser Foundation Health Plan, c1995
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Rectal and colon cancer [sound recording] Source: Memorial Sloan-Kettering Cancer Center; Year: 1976; Format: Sound recording; [New York]: The Center, c1976
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Screening for colon cancer [videorecording] Source: [presented by] the Medical University of South Carolina, College of Medicine and the Health Communications Network; Year: 1993; Format: Videorecording; Charleston, S.C.: The University, c1993
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The molecular basis of reducing colon cancer with aspirin [sound recording]: recorded at DDW 1995 in San Diego Source: AGA; Year: 1995; Format: Sound recording; [Bethesda, Md.]: American Gastroenterological Association, [1995?]
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The role of the physician in long term care [videorecording]; Chemotherapy for elderly colon cancer patients. Year: 2002; Format: Videorecording; Carrollton, TX: HSTN, c2002
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CHAPTER 9. PERIODICALS AND NEWS ON COLON CANCER Overview In this chapter, we suggest a number of news sources and present various periodicals that cover colon cancer.
News Services and Press Releases One of the simplest ways of tracking press releases on colon cancer is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing.
PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “colon cancer” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance.
Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to colon cancer. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “colon cancer” (or synonyms). The following was recently listed in this archive for colon cancer: ·
Receptor may curb growth of colon cancer Source: Reuters Health eLine Date: September 01, 2003 http://www.reutershealth.com/archive/2003/09/01/eline/links/20030901elin011.htm l
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Vaccine may extend colon cancer survival Source: Reuters Health eLine Date: August 19, 2003
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New procedure may better predict colon cancer risk Source: Reuters Health eLine Date: August 05, 2003
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Rofecoxib no aid to chemotherapy in metastatic colorectal cancer Source: Reuters Industry Breifing Date: July 30, 2003
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Death risk higher in obese women with colon cancer Source: Reuters Health eLine Date: July 17, 2003
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Microsatellite-instability status predicts benefit of adjuvant chemotherapy for colon cancer Source: Reuters Industry Breifing Date: July 16, 2003
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Oxaliplatin with fluorouracil-leucovorin effective for progressive colon cancer Source: Reuters Industry Breifing Date: July 11, 2003
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Colon cancer risk reduced by aspirin, gene Source: Reuters Health eLine Date: June 16, 2003
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COX-2 inhibitor use not cost-effective in preventing colon cancer Source: Reuters Industry Breifing Date: June 06, 2003
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Nurses' night shifts linked with colon cancer Source: Reuters Health eLine Date: June 03, 2003
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New colon cancer data stand out at doctors' meeting Source: Reuters Health eLine Date: June 02, 2003
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More meals per day may up men's colon cancer risk Source: Reuters Health eLine Date: May 21, 2003
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Genentech colon cancer drug extends life Source: Reuters Health eLine Date: May 19, 2003
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Growth factor receptor-related protein inhibits colon cancer growth in mice Source: Reuters Industry Breifing Date: May 15, 2003
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Study IDs genes commonly mutated in colon cancer Source: Reuters Health eLine Date: May 08, 2003
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Five-year colon cancer screen may be too frequent Source: Reuters Health eLine Date: April 22, 2003
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Novel combination may be useful against colon cancer Source: Reuters Industry Breifing Date: April 07, 2003
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More men get prostate test than colon cancer screen Source: Reuters Health eLine Date: March 18, 2003
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Many Americans not getting colon cancer screening Source: Reuters Health eLine Date: March 13, 2003
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Blood test may predict colon cancer risk Source: Reuters Health eLine Date: March 13, 2003
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Analysis finds no rise in US colon cancer survival Source: Reuters Health eLine Date: March 10, 2003
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Western diet ups colon cancer risk in women Source: Reuters Health eLine Date: February 11, 2003
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Traveller's diarrhea bug may help treat colon cancer Source: Reuters Health eLine Date: February 10, 2003
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Colon cancer tests don't boost anxiety: study Source: Reuters Health eLine Date: February 10, 2003
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Many docs may misinterpret colon cancer test Source: Reuters Health eLine Date: February 07, 2003
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Folic acid intake tied to colon cancer risk Source: Reuters Health eLine Date: January 09, 2003
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Blood sausage may hinder colon cancer testing Source: Reuters Health eLine Date: December 20, 2002
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Unstable chromosomes could kick off colon cancer Source: Reuters Health eLine Date: November 18, 2002
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Possible link found between virus and colon cancer Source: Reuters Health eLine Date: November 15, 2002
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Ranitidine may improve survival in some cases of colon cancer Source: Reuters Industry Breifing Date: November 07, 2002
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Epigenomics, Mayo Clinic to develop early diagnostic for colorectal cancer Source: Reuters Industry Breifing Date: November 05, 2002
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Women should start colon cancer screening at 50 Source: Reuters Health eLine Date: October 21, 2002
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US colon cancer screening rates slowly improving Source: Reuters Health eLine Date: October 01, 2002
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One bad copy of gene boosts colon cancer risk Source: Reuters Health eLine Date: September 20, 2002
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COX-2 inhibitor prevents liver metastasis of colon cancer in mice Source: Reuters Industry Breifing Date: August 20, 2002
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New pain meds treat spread of colon cancer in mice Source: Reuters Health eLine Date: August 15, 2002
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Small study finds possible link between growth hormone, colon cancer Source: Reuters Industry Breifing Date: July 26, 2002
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Possible link between growth hormone, colon cancer Source: Reuters Health eLine Date: July 26, 2002
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Obesity doubles colon cancer risk in young women Source: Reuters Health eLine Date: July 18, 2002
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Folate supplement may reduce colon cancer risk Source: Reuters Health eLine Date: July 18, 2002
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Recommendations on colon cancer screening updated Source: Reuters Health eLine Date: July 15, 2002
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US Senate committee OKs colon cancer screening bill Source: Reuters Health eLine Date: July 10, 2002
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Keyhole surgery better for colon cancer-study Source: Reuters Health eLine Date: June 28, 2002
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Sanofi completes NDA filing for colon cancer treatment Source: Reuters Industry Breifing Date: June 27, 2002
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Veggies slow spread--not start--of colon cancer Source: Reuters Health eLine Date: June 21, 2002
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Colon cancer in under-50 group relatively rare Source: Reuters Health eLine Date: June 05, 2002
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Immunocytochemical stool test detects colon cancer Source: Reuters Industry Breifing Date: May 30, 2002
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Colorectal cancer screen in risky patients studied Source: Reuters Health eLine Date: May 22, 2002
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Colon cancer screening every 5 years may be OK Source: Reuters Health eLine Date: May 08, 2002
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Colon cancer is deadlier for poor blacks in US Source: Reuters Health eLine Date: April 30, 2002
The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine.
Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name.
Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “colon cancer” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests.
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Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “colon cancer” (or synonyms). If you know the name of a company that is relevant to colon cancer, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.
BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “colon cancer” (or synonyms).
Newsletters on Colon Cancer Find newsletters on colon cancer using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “colon cancer.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” Type “colon cancer” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: ·
Health Benefits of Physical Activity Source: Physical Activity and Fitness Research Digest. 1(1):1-8, February 1993. Summary: The Health Benefits of Physical Activity is a newsletter issue that provides a simple summary of the benefits of physical activity. Section one, Disease Prevention and Treatment, lists the diseases for which regular physical activity can reduce risk, either of getting the disease or of dying from it, and describes how exercise reduces risk for these diseases. Diseases that can be prevented through physical activity include (1) heart disease, (2) stroke, (3) vascular disease, (4) high blood pressure, (5) diabetes, (6) colon cancer, (7) obesity, (8) depression, (9) back pain, and (10) osteoporosis. Physical activity has been shown to have a significant beneficial health effect on individuals suffering from depression. Section two, Health Promotion, discusses the Healthy People 2000 report and its health goals. While physical activity's contribution to quality of life and a personal sense of well-being is more difficult to document than its contribution to prevention and treatment of disease, evidence suggests that humans were designed to be physically active and that physical activity has great potential for enhancing quality of life. Section three, Physical Fitness, examines the relationship between physical activity and physical fitness. Physical fitness has been linked to injury prevention and is often an important factor in the level of body fat, which can affect disease risk. Regular physical activity has positive benefits for both good health and adequate physical fitness.
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Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “colon cancer” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on colon cancer: ·
Link Between Plant-Based Diet and Lowered Risk for Colon Cancer Remains Clear, Convincing Source: AICR Science News. Issue 17, p.1-2. September 2000. Contact: American Institute for Cancer Research. 1759 R St. NW, Washington, DC 20009. (202)328-7744. www.aicr.org. Summary: This article makes the case that the media distorted two articles in the April 20, 2000, issue of the New England Journal of Medicine (NEJM) and gave many Americans misleading impressions about diet and cancer. The studies failed to find a link between recurrence of colon polyps and either low-fat, high-fiber diets featuring fruits and vegetables or diets that included high- fiber cereal supplements. The studies involved only short-term (four-year) adjustments to the diet. Colon cancer is a disease that can take decades to develop. Convincing epidemiological evidence suggests that a healthy diet has its greatest preventive effect as a lifelong commitment. Although it remains to be seen whether four years of fruits, vegetables, whole grains, and beans protect against cancer, there is ample and growing evidence that a lifetime of these foods will.
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Lifestyle Factors and Colon Cancer Risk Source: AICR Science News. Issue 17, p.2. September 2000. Contact: American Institute for Cancer Research. 1759 R St. NW, Washington, DC 20009. (202)328-7744. www.aicr.org. Summary: Researchers analyzed data from a population-based study to determine lifestyle patterns and their association with colon cancer. Data from 1,993 cases and 2,410 controls were grouped by factor analysis to describe various aspects of lifestyle patterns. Among both men and women, a lifestyle characterized by high levels of physical activity showed the strongest inverse association with colon cancer. Additional results from the study point to the importance of maintaining a healthy weight and eating a diet high in plant foods and low in animal products. The authors of the study believe that vigorous physical activity may be the most important component of a healthy lifestyle that decreases risk of colon cancer.
Academic Periodicals covering Colon Cancer Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to colon cancer. In addition to these sources, you can search for articles covering colon cancer that have been published by
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any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for colon cancer. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DIÒ Advice for the PatientÒ can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with colon cancer. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to colon cancer: Capecitabine ·
Systemic - U.S. Brands: Xeloda http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203548.html
Leucovorin ·
Systemic - U.S. Brands: Wellcovorin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202321.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug ConsultÔ Mosby’s Drug ConsultÔ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.
PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html.
Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.
Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to colon cancer by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page
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(http://www.rarediseases.org/search/noddsearch.html), type “colon cancer” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for colon cancer: ·
L-leucovorin (trade name: Isovorin) http://www.rarediseases.org/nord/search/nodd_full?code=195
·
Leucovorin (trade name: Leucovorin calcium) http://www.rarediseases.org/nord/search/nodd_full?code=317
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Leucovorin calcium (trade name: Wellcovorin) http://www.rarediseases.org/nord/search/nodd_full?code=333
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L-leucovorin (trade name: Isovorin) http://www.rarediseases.org/nord/search/nodd_full?code=426
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Interferon alfa-2a (recombinant) (trade name: Roferon-A) http://www.rarediseases.org/nord/search/nodd_full?code=532
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Fluorouracil (trade name: Adrucil) http://www.rarediseases.org/nord/search/nodd_full?code=708
If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: ·
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
12
These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 ·
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
13 Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.
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·
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database
A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “colon cancer” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “colon cancer” (or synonyms) into the “For these words:” box. The following is a sample result: ·
Colorectal Cancer in California, 2001 Source: Sacramento, CA, California Department of Health Services, Cancer Surveillance Section, 101 p., February 2002. Contact: California Department of Health Services, Cancer Surveillance Section, 1700 Tribute Road, Suite 100, Sacramento, CA 95815-4402. (916) 779-0300. INTERNET/EMAIL: http://www.dhs.cahwnet.gov/ps/cdic/cdicindex.htm; http://www.ccreal.org;
[email protected]. Summary: Colorectal Cancer in California, 2001 provides information on the current status of colon and rectum cancer in California. Through this report the California Cancer Registry hopes to promote a better understanding of the epidemiology of colon and rectum cancer in California. Chapters include (1) Colorectal Cancer in California: An Overview; (2) Utilization of Screening Tests for Colon and Rectum Cancer, 19881999: (3) Incidence of Color and Rectum Cancer, 1988-1997; (4) Risk of Developing Invasive Colon and Rectum Cancer in California; (5) Mortality from Cancers of Colon and Rectum in California, 1970-1998; (6) Colon and Rectum Cancer Stage at Diagnosis; and (7) Topographic and Morphologic Features of Colon and Rectum Cancer in California, 1988-1997.
·
Wisconsin Colorectal Cancer Source: Wisconsin Department of Health and Family Services, Bureau of Health Information, Division of Health Care Financing, 19 p., March 2001. Contact: Wisconsin Department of Health and Family Services, Bureau of Health Information, Division of Health Care Financing, P.O. Box 309, Madison, WI 53701-0309. INTERNET/EMAIL: http://www.dhfs.state.wi.us/wcrs/pdf/ WisconsinColorectalCancer.pdf. Summary: Wisconsin Colorectal Cancer provides information on the incidence and mortality of colorectal cancer in Wisconsin based on data from the Wisconsin Cancer Reporting System. Information is also included concerning the national incidence and mortality cancer statistics, risk factors, screening guidelines, current cancer research, and sources for additional information. The purpose of this report is to integrate statistical
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and general educational information in a summary format that is useful to a general audience. The Wisconsin Cancer Reporting System has collected cancer incidence data on Wisconsin residents since 1976. The Wisconsin Behavioral Risk Factor Survey is a representative, statewide telephone survey of Wisconsin household residents age 18 years and over. Known risk factors for colorectal cancer include (1) increasing age, (2) diet high in fat from animal food sources, (3) physical inactivity, (4) obesity, (5) smoking, (6) personal medical history of certain cancers, (7) intestinal polyps, (8) inflammatory bowel disease, and (9) family medical history of certain cancer and genetic conditions. Survival is usually increased when colorectal cancer is identified early and appropriate treatment is received. From 1990 to 1997 in Wisconsin both colorectal cancer incidence rates and mortality rates have declined. Screening tests for colorectal cancer include (1) rectal examination, (2) fecal occult blood test, (3) sigmoidoscopy, (4) colonoscopy, and (5) double contrast barium enema. Women taking hormone replacement therapy (HRT) had a 46 percent lower incidence of colon cancer than those not taking HRT after menopause. A list provides additional sources of information. 2 figures, 5 tables, 44 references. ·
Colorectal Cancer: The Importance of Early Detection: At-a-glance 1999 Source: Atlanta, GA, Centers for Disease Control and Prevention, 4 p., 1999. Contact: Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Mail Stop K-64, 4770 Buford Highway NE., Atlanta, GA 30341-3717. (770) 488-4751. FAX: (770) 488-4760. INTERNET/EMAIL: www.cdc.gov/cancer;
[email protected]. Summary: Colorectal Cancer: The Importance of Early Detection: At-a-glance 1999 is a fact sheet that provides early detection data, types of screening, guidelines for screening, and Centers for Disease Control and Prevention (CDC) program activities for colorectal cancer. Colorectal cancer is the second leading cause of cancer-related death in the United States. Blacks are more likely than whites to be diagnosed with colorectal cancer and to die from it. Risk factors include (1) advancing age, (2) having inflammatory bowel disease, (3) family history, (4) certain heredity syndromes, (5) physical inactivity, (6) low fruit and vegetable intake, (7) a diet low in fiber and high in fat, (8) obesity, and (9) alcohol use. Early detection is the key to survival. Two tests that have been shown to be beneficial in screening for colorectal cancer are (1) fecal occult blood test (FOBT), and (2) flexible sigmoidoscopy. Colonoscopy, double-contrast barium enema (DCBE), and digital rectal examination are also used, but their efficacy has not yet been shown clinically. Currently, screening for colorectal cancer lags behind screening for other cancers. Current colorectal cancer screening guidelines are (1) annual FOBT, (2) flexible sigmoidoscopy every 5 years, and (3) total colon examination by colonoscopy every 10 years or by DCBE every 5 to 10 years. The CDC is promoting colorectal cancer screening nationwide by educating health care providers and the public about the benefits of screening, the availability of screening, and current screening guidelines.
·
Colorectal Cancers in Pennsylvania Source: Harrisburg, PA, Pennsylvania Department of Health, Division of Health Statistics, 2 p., October 1998. Contact: Pennsylvania Department of Health, Division of Health Statistics, 555 Walnut Street, 6th Floor, Harrisburg, PA 17101-1900. (717) 783-2548. FAX: (717) 772-3258. INTERNET/EMAIL: www.health.state.pa.us/hpa/Stats/stat_res.htm.
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Summary: Colorectal Cancers in Pennsylvania provides statistics on colorectal cancer incidence, mortality, and risk factors. Colorectal cancers are the second most common cancer diagnosed among women and the third most common among men in Pennsylvania. Colorectal cancers are the third most common cause of cancer deaths among both men and women in the commonwealth. The annual incidence, death rates, and age-adjusted rates declined from 1985 to 1995. Between 1985 and 1995, there was an increase in the percentage of colon and rectum cancer cases diagnosed at the in situ stage of the disease among Pennsylvania residents, from 5.6 percent in 1985 to 8.7 percent in 1995. The percentage of distance stage diagnoses declined from 17.5 percent to 16.7 percent. However, the percentage of colorectal cancer cases diagnosed at the local and regional stages of the disease has not changed. The Department of Health recommends use of an annual fecal occult blood test and/or periodic flexible sigmoidoscopy for all persons age 50 and older. The American Cancer Society also recommends that digital rectal exam be done at the same time as a sigmoidoscopy. Results from the 21,996 statewide sample telephone survey conducted by the Pennsylvania Department of Health's Behavioral Risk Factor Surveillance system showed that 27 percent of Pennsylvania adults age 50 and older had taken a home fecal occult blood test in the past 2 years, and 44 percent had had a digital rectal exam in the past year. 6 figures. ·
Cost-effectiveness of Colorectal Cancer Screening Source: American Digestive Health Foundation, 3 p., 1998. Contact: American Digestive Health Foundation, INTERNET/EMAIL: http://www.gastro.org/adhf/cc-costeff.html. Summary: Cost-effectiveness of Colorectal Cancer Screening provides information on the cost-effectiveness of screening for colorectal cancer. Research indicates that screening of asymptomatic people at average risk for colorectal cancer, beginning at age 50 years, can reduce mortality from the disease. An additional benefit from screening is the identification and removal of premalignant polyps. Data suggest that screening is cost-effective relative to other common medical interventions, and there is a substantial cost in not screening. When analyzing the cost of colon screening, it is important to consider colon screening as a program that includes repeated screening at intervals after a negative initial screening test, evaluation of positive tests, and care if cancer is discovered. If screening is not done at all, or screening compliance is poor, there are predictable rates of cancer development and death.
The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “colon cancer” (or synonyms) into the search box and click “Search.” The results will
15 16
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).
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be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 48117 319 219 21 9 48685
HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “colon cancer” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/. 17
Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.
18
The HSTAT URL is http://hstat.nlm.nih.gov/.
19
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 21 The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: ·
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
·
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Colon Cancer In the following section, we will discuss databases and references which relate to the Genome Project and colon cancer.
Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “colon cancer” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for colon cancer: ·
Colon Cancer, Familial Nonpolyposis, Type 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?120435
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Colon Cancer, Familial Nonpolyposis, Type 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?120436
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Colorectal Cancer, Hereditary Nonpolyposis Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?114500
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Leukemia, Acute Myelocytic, with Polyposis Coli and Colon Cancer Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?246470
23
Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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Genes and Disease (NCBI - Map) The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: ·
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
·
Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
·
Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
·
Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
·
Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
·
Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
·
Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html
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Entrez Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: ·
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
·
Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
·
Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
·
Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
·
Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “colon cancer” (or synonyms) into the search box and click “Go.”
Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually 24 Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html.
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limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “colon cancer” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
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Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on colon cancer can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to colon cancer. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly.
The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below.
Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to colon cancer. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “colon cancer”:
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Guides on colon cancer Colon Cancer http://www.nlm.nih.gov/medlineplus/tutorials/whatiscoloncancerloader.html
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Other Guides Bladder Cancer http://www.nlm.nih.gov/medlineplus/bladdercancer.html Breast Cancer http://www.nlm.nih.gov/medlineplus/breastcancer.html Cancer http://www.nlm.nih.gov/medlineplus/cancergeneral.html Carcinoid Tumors http://www.nlm.nih.gov/medlineplus/carcinoidtumors.html Colonic Diseases http://www.nlm.nih.gov/medlineplus/colonicdiseasesgeneral.html Colonic Polyps http://www.nlm.nih.gov/medlineplus/colonicpolyps.html Colorectal Cancer http://www.nlm.nih.gov/medlineplus/colorectalcancer.html Digestive Diseases http://www.nlm.nih.gov/medlineplus/digestivediseasesgeneral.html Ovarian Cancer http://www.nlm.nih.gov/medlineplus/ovariancancer.html Ovarian Cancer http://www.nlm.nih.gov/medlineplus/tutorials/whatisovariancancerloader.html Pancreatic Cancer http://www.nlm.nih.gov/medlineplus/pancreaticcancer.html Stomach Cancer http://www.nlm.nih.gov/medlineplus/stomachcancer.html Vulvar Cancer http://www.nlm.nih.gov/medlineplus/vulvarcancer.html
Within the health topic page dedicated to colon cancer, the following was listed: ·
General/Overviews Colon Cancer http://www.nlm.nih.gov/medlineplus/tutorials/whatiscoloncancerloader.html Colorectal Cancer Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00035 Facts about Colorectal Cancer Source: American Gastroenterological Association http://www.gastro.org/phys-sci/fact-cc.html
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What Is Colon and Rectum Cancer? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_is_colon_and_rectu m_cancer.asp?sitearea=cri ·
Diagnosis/Symptoms Barium Enema Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=SA00003 Colonoscopy http://www.nlm.nih.gov/medlineplus/tutorials/colonoscopyloader.html Colonoscopy Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/colonoscopy/index.htm Elimination Problems: Self-Care Flowcharts Source: American Academy of Family Physicians http://familydoctor.org/flowcharts/532.html Fecal Occult Blood Test Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=SA00002 Flexible Sigmoidoscopy Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=SA00004 How Is Colon and Rectum Cancer Diagnosed? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_colon_and_re ctum_cancer_diagnosed.asp How Is Colon and Rectum Cancer Staged? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_colon_and_re ctum_cancer_staged.asp Sigmoidoscopy http://www.nlm.nih.gov/medlineplus/tutorials/sigmoidoscopyloader.html
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Treatment Anal Cancer (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/anal/patient/ Bevacizumab (Avastin) for Metastatic Colorectal Cancer: Treatment Referral Center Protocol Source: National Cancer Institute http://www.cancer.gov/newscenter/pressreleases/bevacizumab Biological Therapies: Using the Immune System to Treat Cancer Source: National Cancer Institute http://cis.nci.nih.gov/fact/7_2.htm
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Colon Cancer (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/colon/patient/ Colon Cancer Surgery http://www.nlm.nih.gov/medlineplus/tutorials/coloncancersurgeryloader.html Ileostomy, Colostomy and Ileoanal Reservoir Surgery Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/ileostomy/index.htm Laparoscopic Intestinal Surgery: A Guide for Patients Source: Cleveland Clinic Foundation http://www.clevelandclinic.org/health/healthinfo/docs/0900/0962.asp?index=4356 Questions and Answers about Eloxatin (Oxaliplatin for Injection) Source: Food and Drug Administration http://www.fda.gov/cder/drug/infopage/eloxatin/eloxatinQA.htm Rectal Cancer (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/rectal/patient/ Treatment by Stage of Colon Cancer Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_4X_Treatment_by_Stage_ of_Colon_Cancer.asp?sitearea= Treatment by Stage of Rectum Cancer Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_4X_Treatment_by_Stage_ of_Rectum_Cancer.asp?sitearea= ·
Specific Conditions/Aspects Few Words about “The Risk of Getting an Infection From an Endoscope” Source: American Society for Gastrointestinal Endoscopy http://www.asge.org/gui/patient/gea_inf_risk.asp Medicare Coverage for Colonoscopy Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_3x_Medicare_Coverage_f or_Colonoscopy.asp Notice to Medicare Beneficiaries: New Colorectal Cancer Screening Benefit Begins July 1, 2001 Source: American Gastroenterological Association http://www.gastro.org/public/medicare_beneficiaries.html What Should You Ask Your Doctor about Colon and Rectum Cancer? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_5X_What_should_you_as k_your_doctor_about_colon_and_rectum_cancer.asp
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From the National Institutes of Health What You Need to Know about Cancer of the Colon and Rectum Source: National Cancer Institute http://www.cancer.gov/cancerinfo/wyntk/colon-and-rectum
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Latest News Chemotherapy plus Radiation Best for Rectal Cancer Source: 09/17/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14006 .html Receptor May Curb Growth of Colon Cancer Source: 09/01/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_13853 .html Virtual Colonoscopy Not Ready for Widespread Use Source: 09/05/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_13890 .html
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Men 6 Questions That Could Save Your Life (Or the Life of Someone You Love): What Women Need to Know about Colon Cancer Screening Source: American Society for Gastrointestinal Endoscopy http://www.asge.org/gui/patient/6questions.asp
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Organizations American Cancer Society http://www.cancer.org/ American Gastroenterological Association http://www.gastro.org/ National Cancer Institute http://www.cancer.gov/ National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/
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Pictures/Diagrams Illustrated Colon http://www.asge.org/gui/patient/colondrawing.pdf
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Prevention/Screening Can Colon and Rectum Cancer Be Found Early? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_Can_colon_and_rectu m_cancer_be_found_early.asp
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Can Colon and Rectum Cancer Be Prevented? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_2X_Can_colon_and_rectu m_cancer_be_prevented.asp Colon Cancer Screening: More Data for the Debate on Colonoscopy Source: National Cancer Institute http://www.cancer.gov/clinicaltrials/results/colonoscopy0700 Colorectal Cancer (PDQ): Prevention Source: National Cancer Institute http://cancer.gov/cancerinfo/pdq/prevention/colorectal/patient/ Colorectal Cancer Screening: What's Best for Me? Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/takecharge/healthdecisionguides/ccs/index.cfm Colorectal Cancer Screening: Questions and Answers Source: National Cancer Institute http://cis.nci.nih.gov/fact/5_31.htm Colorectal Cancer: Facts on Screening Source: National Center for Chronic Disease Prevention and Health Promotion http://www.cdc.gov/cancer/screenforlife/fs_detailed.htm Screening for Colorectal Cancer: Recommendations from the United States Preventive Services Task Force Source: American College of Physicians http://www.annals.org/cgi/content/full/137/2/I-38 ·
Research Anal Cancer Precursors in Persons with HIV Infection Source: American College of Physicians http://www.annals.org/cgi/content/full/138/6/I-44 Another Study Suggests Milk May Lower Colon Cancer Risk Source: Cancer Research Foundation of America http://www.crfa.org/healthyliving/PreventionNews/milk-may-lower-coloncancer-risk.cfm Bevacizumab (Avastin) Improves Survival in Metastatic Colorectal Cancer Source: National Cancer Institute http://www.cancer.gov/clinicaltrials/results/bevacizumab-and-colorectalcancer0601 Fiber May Not Reduce Colon Cancer Risk, But It's Still Good for You Source: American Cancer Society http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Fiber_May_Not_Redu ce_Colon_Cancer_Risk.asp National Cancer Institute Trial Yields New Data on Colon Cancer Screening Test Source: National Cancer Institute http://www.cancer.gov/newscenter/pressreleases/PLCO NCI Planning Study of Bevacizumab (Avastin) for Metastatic Colorectal Cancer Source: National Cancer Institute http://www.cancer.gov/newscenter/pressreleases/avastin
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NCI-Funded Clinical Trials Show Aspirin Reduces Recurrence of Polyps Source: National Cancer Institute http://www.cancer.gov/newscenter/pressreleases/aspirin New Drug Holds Promise for Metastatic Colorectal Cancer Source: American Cancer Society http://www.cancer.org/docroot/NWS/content/NWS_1_1x_New_Drug_Holds_Pr omise_For_Metastatic_Colorectal_Cancer.asp No Increased Benefit from Chemotherapy Given Directly into Liver Source: American Cancer Society http://www.cancer.org/docroot/NWS/content/NWS_1_1x_No_Increased_Benefit _Seen_For_Chemotherapy_Given_Directly_Into_The_Liver.asp What's New in Colon and Rectum Cancer Research and Treatment? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_6x_whats_new_in_colon_an d_rectum_cancer_research_and_treatment.asp ·
Statistics Colorectal Cancer Screening Source: Centers for Disease Control and Prevention http://www.cdc.gov/od/oc/media/pressrel/fs030314.htm Colorectal Cancer: The Importance of Prevention and Early Detection Source: Centers for Disease Control and Prevention http://www.cdc.gov/cancer/colorctl/colorect.htm What Are the Key Statistics for Colon and Rectum Cancer? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_sta tistics_for_colon_and_rectum_cancer.asp
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Women 6 Questions That Could Save Your Life (Or the Life of Someone You Love): What Women Need to Know about Colon Cancer Screening Source: American Society for Gastrointestinal Endoscopy http://www.asge.org/gui/patient/6questions.asp
You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on colon cancer. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general
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Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: ·
Understanding Colon Cancer Screening Source: Manchester, MA: American Society for Gastrointestinal Endoscopy. 2001. [2 p.]. Contact: Available from American Society for Gastrointestinal Endoscopy. 13 Elm Street, Manchester, MA 01944. (508) 526-8330. PRICE: Single copy free. Summary: This brochure educates readers about colon cancer screening. The brochure offers six True or False statements about colorectal cancer (CRC) screening, then explains the correct answer for each. Topics include the incidence of CRC in men versus women; the indications for testing; the time involved in a colonoscopy screening examination; the mortality associated with CRC; diagnostic tests used to screen for colon cancer; and prevention of CRC. Colorectal cancer affects an equal number of men and women. Beginning at age 50, all men and women should be screened for colorectal cancer, even if they are experiencing no problems or symptoms. Colonoscopy is almost always done on an outpatient basis; the test is safe and the procedure itself typically takes less than 30 minutes. Colorectal cancer is the third leading cause of cancer deaths in women in the United States. Tests used for screening for CRC include digital rectal exam, stool blood test, barium enema, flexible sigmoidoscopy, and colonoscopy. The brochure emphasizes that colon cancer is often preventable, so screening is very important.
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Colon Book: A Look at Polyps and Colon Cancer, Their Treatment, and Your Prospects for Recovery. [Folleto del Colon: Que Son los Polipos y el Cancer del Colon, Sus Tratamientos y las Probabilidades de Source: San Bruno, CA: StayWell Company. 1999. 15 p. Contact: Available from Staywell Company. Order Department, 1100 Grundy Lane, San Bruno, CA 94066-9821. (800) 333-3032. Fax (650) 244-4512. PRICE: $1.25 per copy; plus shipping and handling. Summary: This patient education brochure describes colon polyps and colon cancer, their treatment, and prognosis. Written in nontechnical language, the brochure notes that it can be quite unsettling when a doctor suspects that the patient has a growth in their colon. However, most colon growths can be removed swiftly. And even if the growth is cancerous, with early medical treatment, prognosis is good. A prompt evaluation is the key to diagnosing a colon growth. A medical history, thorough exam, and diagnostic tests (including digital rectal exam, sigmoidoscopy, barium enema, and colonoscopy) help the doctor diagnose the colon problem and plan the right treatment. Surgical treatment may involve removal of the colon growth or growths; if cancer is found, further treatment (such as chemotherapy or radiation) may be needed. After recovery from surgery and any other treatments, the patient can slowly return to their daily activities. Followup exams, a healthy diet, and help from friends, family, and support groups can help the patient get back to his or her routine as quickly as possible. One section of the brochure illustrates and describes the healthy colon, how it functions, and how unhealthy growths (polyps and cancer) can occur. The brochure then describes preoperative care, the different types of colon resections that may be utilized (right hemicolectomy, transverse colectomy, left colectomy, and sigmoid colectomy), what to expect during the hospital stay, and postoperative recovery at home. The brochure is
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illustrated with full color line drawings and is available in English or Spanish. 12 figures. ·
ACG Recommendations on Colorectal Cancer Screening for Average and Higher Risk Patients in Clinical Practice Source: Arlington, VA: American College of Gastroenterology. 200x. 25 p. Contact: Available from American College of Gastroenterology. 4900 B South 31st Street, Arlington, VA 22206-1656. (703) 820-7400. Fax (703) 931-4520. PRICE: Single copy free. Summary: This booklet outlines the preferred colorectal cancer screening recommendations of the American College of Gastroenterology (ACG) and presents an update of the ACG position on screening as outlined by the Agency for Healthcare Policy and Research (AHCPR). The AHCPR's recommendations presented a menu of options for screening average risk persons. These options have similar cost-effectiveness ratios, however, there are substantial differences between the various options regarding their effectiveness, initial costs, and to a lesser degree, risk. The ACG continues to endorse the AHCPR guideline. The update recommendation as presented in the booklet is meant to reflect trends in the rapidly changing perceptions of colorectal cancer prevention strategies among clinical gastroenterologists in both academic and private practice. The preferred screening strategy for persons over age 50 at average risk for colorectal cancer is colonoscopy every 10 years. An alternative strategy for this population (used when resources, expertise, or reimbursement for screening colonoscopy are not available) is flexible sigmoidoscopy every 5 years plus annual fecal occult blood testing. The booklet outlines other screening strategies include barium enema, and CT (computed tomography) and magnetic resonance (MR) colonography (also called virtual colonoscopy). The booklet then discusses screening for people in high risk categories, including those with a personal or family history of familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, and strong family history of colon cancer. The booklet includes extensive tables that summarize the information and guidelines presented in the text. 2 figures. 4 tables. 142 references.
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Now Medicare Covers a Test That Could Save Your Life: What You Should Know About New Medicare Colorectal Cancer Screening Benefit [and] Screening for Your Family Source: Arlington, VA: American College of Gastroenterology. 1998. 6 p. Contact: Available from American College of Gastroenterology. 4900 B South 31st Street, Arlington, VA 22206. (800) 478-2876. PRICE: Single copy free. Summary: This brochure describes colorectal cancer screening and new Medicare reimbursement (payment) for its costs. Screening can prevent cancer by removing precancerous growths (polyps), and early detection allows diagnosis before cancers have a chance to spread. Up to 80 percent of colon cancer deaths can be prevented by timely removal of precancerous polyps. Congress passed a new law which directed Medicare to pay for three tests for colorectal cancer screening. Fecal occult blood tests will be paid for annually; flexible sigmoidoscopy will be paid for once every four years for average risk patients; and screening colonoscopy will be paid for once every two years for high risk patients. The brochure describes each of these tests, as well as barium X-ray, noting the advantages and disadvantages of each. High risk patients are those who have a personal history of adenomatous polyps, colorectal cancer, or inflammatory bowel disease (Crohn's disease or ulcerative colitis; those who have a close relative who has had colorectal cancer or an adenomatous polyp; and those who have a family history of
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familial adenomatous polyposis or of hereditary non-polyposis colorectal cancer. The brochure concludes with information about choosing a physician to do these screening tests. A physician's insert is provided with the brochure; the insert lists the HCPCS Codes and Guidelines for Reimbursement for colorectal cancer screening tests. (AA-M). ·
Colorectal Cancer Screening: Early Detection Source: San Ramon, CA: Health Information Network, Inc. 1996. 14 p. Contact: Available from HIN, Inc. 231 Market Place, Number 331, San Ramon, CA 94583. (800) HIN-1121. Fax (925) 358-4377. Website: www.hinbooks.com. PRICE: $1.95 suggested list price; professional and bulk discounts available. Order number 206. ISBN: 1885274629. Summary: This brochure provides readers with basic information about screening for colorectal cancer. The brochure defines a screening test as a type of medical examination that may find cancer early, before it causes symptoms or pain. Colorectal cancer is cancer in any part of the large intestine, which includes the colon and rectum. Colorectal cancer is one of the most curable types of cancer, with a success rate of over 90 percent when found in its early stages. Written in language that is easy to read, the brochure covers the anatomy of the colon and rectum, the nature of cancer, risk factors for colorectal cancer, screening tests for colorectal cancer (fecal occult blood test, flexible sigmoidoscopy, colonoscopy, barium enema with air contrast examination, and digital rectal examination), symptoms of colorectal cancer, and patient followup. The brochure provides the addresses and phone numbers of the American Cancer Society and the National Cancer Institute. A brief glossary of terms is also included.
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Colorectal Cancer: Questions and Answers Source: Arlington Heights, IL: American Society of Colon and Rectal Surgeons. 1996. [2 p.]. Contact: Available from American Society for Colon and Rectal Surgeons (ASCRS). 85 West Algonquin Road, Suite 550, Arlington Heights, IL 60005. (800) 791-0001 or (847) 290-9184. Website: www.fascrs.org. PRICE: Single copy free. Summary: This brochure describes colorectal cancer, the second most common cancer in the United States, striking 140,000 people annually and causing 60,000 deaths. The author stresses that the disease is potentially curable if diagnosed in the early stages. Risk factors include age, family history of colorectal cancer and polyps, and personal history of ulcerative colitis, colon polyps, or cancer of other organs, especially of the breast or uterus. Nearly all colon and rectal cancer begins in benign polyps; these premalignant growths occur on the bowel wall and may eventually increase in size and become cancer. The most common symptoms are rectal bleeding and changes in bowel habits, such as constipation or diarrhea. Unfortunately, many polyps and early cancers fail to produce symptoms. Therefore, routine physicals should include colorectal cancer detection procedures after age 40, including digital rectal exams, a chemical test of stool for blood, and sigmoidoscopy (the inspection of the lower bowel with a lighted tubular instrument). Colorectal cancer requires surgery in nearly all cases for a complete cure. Radiation and chemotherapy are sometimes used in addition to surgery. The brochure also outlines steps that can reduce the risk of contracting colon cancer. One way is having benign polyps removed by an outpatient procedure called colonoscopy. There is also some evidence that diet (high fiber, low fat) may play a significant role in preventing colorectal cancer. Readers are also encouraged to pay attention to changes in
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their bowel habits. The brochure concludes with a brief description of the specialty of colon and rectal surgeons. 1 figure. ·
Follow Up Evaluation After Surgery for Colorectal Cancer: Questions and Answers Source: Arlington Heights, IL: American Society of Colon and Rectal Surgeons. 1996. 4 p. Contact: Available from American Society of Colon and Rectal Surgeons. 85 West Algonquin Road, Suite 550, Arlington Heights, IL 60005. (800) 791-0001 or (847) 2909184. Fax (847) 290-9203. E-mail:
[email protected]. Website: www.fascrs.org. PRICE: Full-text available online at no charge; Single copy free; bulk copies available. Summary: This patient education brochure provides information about patient followup evaluations after surgery for colorectal cancer. Written in a question and answer format, the brief brochure discusses the reasons why follow-up evaluations are crucial, the recommended length of a followup program, what to expect at a followup visit, and the importance of screening close family members who are at increased risk for colon and rectal cancer.
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Talk about colorectal cancer with your health care provider Source: Washington, DC: National Alliance for Hispanic Health. [2002]. 4 pp. Contact: Available from National Alliance for Hispanic Health, 1501 16th Street, N.W, Washington, DC 20036-1401. Telephone: (202) 387-5000 / fax: (202) 797-4353 / e-mail:
[email protected] / Web site: http://www.hispanichealth.org/. Available at no charge; also available from the Web site at no charge. Summary: This brochure, available in both English and Spanish, describes colorectal cancer, explains why screening is important for Hispanics, explains how screening for colorectal cancer can be performed, offers information on who should be screened, and provides contact information for low-cost screening alternatives.
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Colorectal Cancer: The Importance of Prevention and Early Detection: At a Glance, 2001 Source: Atlanta, GA, Centers for Disease Control and Prevention, 4 p., 2001. Contact: Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Mail Stop K-64, 4770 Buford Highway, NE., Atlanta, GA 30341-3717. (770) 488-4751. FAX: (770) 488-4760. INTERNET/EMAIL: http://www.cdc.gov/cancer; http://www.cdc.gov/cancer/colorctl/colopdf/colaag01.pdf;
[email protected]. Summary: Colorectal Cancer: The Importance of Prevention and Early Detection: At a Glance, 2001 describes the burden of colorectal cancer in the United States, prevention and early detection methods, screening guidelines, screening behavior, and Centers for Disease Control and Prevention activities targeting colorectal cancer. Colorectal cancer is the second leading cause of cancer-related death in the United States. The American Cancer Society estimates that 56,700 Americans will die of colorectal cancer in 2001, while another 135,400 will be diagnosed. Colorectal cancer risk increases with age. Other risk factors include having (1) inflammatory bowel disease, (2) a personal family history of colorectal cancer or colorectal polyps, and (3) certain hereditary syndromes. Other factors include (1) physical inactivity; (2) a diet low in fruits, vegetables, and fiber; (3) a diet high in fat; (4) obesity; (5) alcohol consumption; and (6) tobacco use. Two tests have
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been shown to be beneficial in screening for colorectal cancer: (1) Fecal occult blood test (FOBT), and (2) flexible sigmoidoscopy. Two other tests, colonoscopy and doublecontrast barium enema, are also commonly used by physicians. Current guidelines are for regular screening for all adults age 50 years and older. Recommended screening procedures include (1) FOBT ever year, (2) flexible sigmoidoscopy every 5 years, and (3) total colon examination by colonoscopy every 10 years or by double-contrast barium enema every 5 to 10 years. Persons at higher risk should begin screening at a younger age and should be tested more often. Screening for colorectal cancer lags far behind that for other cancers. This underscores the need to increase awareness and promote the use of colorectal cancer screening at regular examinations. The CDC is involved in colorectal cancer prevention and early detection through national and state partnerships, promotion of colorectal cancer screening, education and training, and surveillance and research. ·
Screening for Colorectal Cancer Source: Leawood, KS, American Academy of Family Physicians, 2 p., 2000. Contact: American Academy of Family Physicians, P.O. Box 11210, Shawnee Mission, KS 66207-1210. (800) 274-2237; (913) 906-6000. INTERNET/EMAIL: http://www.familydoctor.org;
[email protected]. Summary: Screening for Colorectal Cancer is a fact sheet that presents information related to colorectal cancer, the leading cause of cancer deaths in the United States. With early detection, colorectal cancer can generally be cured by surgery. Most colorectal cancers begin as a harmless polyp. Signs of colorectal cancer include (1) bleeding from the rectum, (2) blood in stool or toilet after a bowel movement, (3) change in shape of the stool, (4) cramping in the lower stomach, and (5) discomfort or an urge to have a bowel movement when there is no need to have one. Screening tests for colorectal cancer include (1) digital rectal examination, (2) fecal occult blood testing, (3) flexible sigmoidoscopy, (4) double-contrast barium enema, and (5) colonoscopy. As colorectal cancer is most common in older adults, doctors generally screen patients after age 50 years. Screening should occur at a younger age if the person has (1) a history of colorectal cancer or large polyps, (2) a close relative with the disease, (3) ulcerative colitis or Crohn's disease, or (4) a hereditary colon cancer syndrome. Screening recommendations for people over age 49 years include (1) fecal occult blood testing every year, (2) flexible sigmoidoscopy every 5 years, (3) fecal occult blood testing every year and flexible sigmoidoscopy every 5 years, (4) double-contrast barium enema every 5 to 10 years, or (5) colonoscopy every 10 years.
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Colorectal Cancer Screening and Early Detection Source: Atlanta, GA, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, 2 p., February 18, 1999. Contact: Centers for Disease Control and Prevention, Office of Communication, Division of Media Relations. 1600 Clifton Road, MS D-25, Atlanta, GA 30333. (404) 639-3286. FAX: (404) 639-7394. INTERNET/EMAIL: http://www.cdc.gov/od/oc/media/fact/colorect.htm. Summary: Colorectal Cancer Screening and Early Detection is a fact sheet that provides information on colorectal cancer screening. Topics include (1) the incidence of cancer of the colon or rectum, (2) screening to identify polyps or early cancer, (3) insurance coverage for colorectal cancer screening, (4) age as a risk factor for colorectal cancer, (5) the increased risk for African Americans, (6) family history as a risk factor, and (7)
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recommendations for screening. The Centers for Disease Control and Prevention, the Health Care Financing Administration, and the National Cancer Institute recommend all men and women age 50 years and older consult their doctors about the best screening test options for them. ·
Screening for Colorectal Cancer: Recommendation and Rationale Source: American Family Physician. 66(12): 2287-2290. December 15, 2002. Contact: Available from American Academy of Family Physicians. 8880 Ward Parkway, Kansas City, MO 64114-2797. (800) 274-2237. Summary: This statement summarizes for family care practitioners the current United States Preventive Services Task Force (USPSTF) recommendation on screening for colorectal cancer and the supporting scientific evidence. The complete statement is available at www.preventiveservices.ahrq.gov and through the National Guideline Clearinghouse (www.guideline.gov). The USPSTF strongly recommends that clinicians screen men and women 50 years of age or older for colorectal cancer. This article then reviews the clinical considerations that accompany this recommendation. The article concludes with a brief section on the recommendations of other groups, including the American Cancer Society. 2 tables. 10 references.
The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “colon cancer” (or synonyms). The following was recently posted: ·
2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology Source: American Society of Clinical Oncology - Medical Specialty Society; 1997 (revised 2001 Mar); 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2746&nbr=1972&a mp;string=colon+AND+cancer
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ACR Appropriateness Criteria for pre-treatment staging of colorectal cancer Source: American College of Radiology - Medical Specialty Society; 1996 (revised 1999); 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2400&nbr=1626&a mp;string=colon+AND+cancer
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Adjuvant therapy for stage II colon cancer following complete resection Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 1997 August 25 (updated online 2000 Apr); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3009&nbr=2235&a mp;string=colon+AND+cancer
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Adjuvant therapy for stage III colon cancer following complete resection Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 1997 August 25 (updated online 2000 Apr); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3016&nbr=2242&a mp;string=colon+AND+cancer
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American Gastroenterological Association medical position statement: hereditary colorectal cancer and genetic testing Source: American Gastroenterological Association - Medical Specialty Society; 2001 April 18; 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3057&nbr=2283&a mp;string=colon+AND+cancer
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American Gastroenterological Association medical position statement: impact of dietary fiber on colon cancer occurrence Source: American Gastroenterological Association - Medical Specialty Society; 1999 November 15 (reviewed 2001); 2 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3070&nbr=2296&a mp;string=colon+AND+cancer
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Colorectal cancer screening Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1995 May (revised 2002 Jun); 45 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3406&nbr=2632&a mp;string=colon+AND+cancer
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Colorectal cancer screening and surveillance: clinical guidelines and rationale-update based on new evidence Source: American College of Gastroenterology - Medical Specialty Society; 1997 February (revised 2003 Feb); 48 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3686&nbr=2912&a mp;string=colon+AND+cancer
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Prevention and screening of colorectal cancer Source: Finnish Medical Society Duodecim - Professional Association; 2002 April 27; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3397&nbr=2623&a mp;string=colon+AND+cancer
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Preventive health care, 2001 update: colorectal cancer screening Source: Canadian Task Force on Preventive Health Care - National Government Agency [Non-U.S.]; 2001; 2 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2894&nbr=2120&a mp;string=colon+AND+cancer
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Recommended colorectal cancer surveillance guidelines by the American Society of Clinical Oncology. Source: American Society of Clinical Oncology - Medical Specialty Society; 1999 April (revised 2000 Oct); 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1885&nbr=1111&a mp;string=colon+AND+cancer
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Screening for colorectal cancer: recommendations and rationale Source: United States Preventive Services Task Force - Independent Expert Panel; 1996 (revised 2002 Jul); 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3285&nbr=2511&a mp;string=colon+AND+cancer
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Use of irinotecan (Camptosar®, CPT-11) combined with 5-fluorouracil and leucovorin (5FU/LV) as first-line therapy for metastatic colorectal cancer Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 2001 October 23 (updated online 2003 Feb); 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3763&nbr=2989&a mp;string=colon+AND+cancer
Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: ·
Colon Cancer Summary: Also available In: Source: Federation of Chinese American and Chinese Canadian Medical Societies http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7272
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What You Need To Know About™ Cancer of the Colon and Rectum Summary: This booklet on colon cancer discusses symptoms, diagnosis, treatment, emotional issues, and questions to ask the doctor. Source: Cancer Information Service, National Cancer Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7120 The NIH Search Utility
The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to colon cancer. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.
Additional Web Sources
A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: ·
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDÒHealth: http://my.webmd.com/health_topics
Associations and Colon Cancer The following is a list of associations that provide information on and resources relating to colon cancer: ·
Cancer Information Service at Imperial Cancer Research Fund Telephone: 020-72693142 Fax: 020-72692865 Email:
[email protected] Web Site: http://www.imperialcancer.co.uk Background: Imperial Cancer Research Fund is a registered charity in the United Kingdom dedicated to saving lives through research into the causes, prevention,
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treatment, and cure of cancer. Employing more than 1,000 scientific and clinical staff members in its laboratories, and at clinical units and universities, it undertakes more than one-third of all cancer research in the UK. The Cancer Information Service at Imperial Cancer Research Fund is run by specialist nurses for anyone who has questions or concerns about cancer. The service is open Monday through Friday, from 9 a.m. To 5 p.m. ·
Carcinoid Cancer Foundation, Inc Telephone: (914) 683-1001 Toll-free: (888) 722-3132 Fax: (914) 683-5919 Email:
[email protected] Web Site: http://www.carcinoid.org Background: The Carcinoid Cancer Foundation, Inc. is a not-for-profit organization dedicated to encouraging and supporting research and education concerning carcinoid tumors and carcinoid syndrome. A carcinoid tumor is a rare, slow growing form of cancer characterized by overgrowth of certain cells that secrete serotonin, a naturally occurring derivative of the amino acid tryptophan. Serotonin has many functions including regulating activity of the intestinal tract. In some cases, individuals with carcinoid tumors may experience abnormally increased secretion of serotonin, resulting in carcinoid syndrome. In individuals with carcinoid syndrome, associated symptoms may include intense flushing of the face and upper body, wheezing, weight loss, severe diarrhea, and, in some cases, ulcer-like symptoms and/or eventual heart failure. The Carcinoid Cancer Foundation was established in 1968 to support research that will improve the understanding, diagnosis, and treatment of carcinoid tumor and carcinoid syndrome. The Foundation also provides understandable information to affected individuals and family members, engages in professional education, and offers networking services to affected families. In addition, the Carcinoid Cancer Foundation has a web site on the Internet that answers 'frequently asked questions' (FAQ) on carcinoid tumor and carcinoid syndrome; offers comprehensive information on diagnosis and treatment; provides dynamic linkage to support organizations, discussion groups, related web sites, and transportation assistance organizations; and offers information on current research and references.
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David G. Jagelman Inherited Colorectal Cancer Registries Telephone: (216) 444-6470 Toll-free: (800) 998-4785 Fax: (216) 445-6935 Email:
[email protected] Background: Established in 1978, the David G. Jagelman Inherited Colorectal Cancer Registries is a not-for-profit academic medical center recognized as a National Referral Center and an international resource for diseases of the colon and rectum. Dedicated to identifying, educating, and serving affected individuals, the organization has an educational division, a research institute, and a hospital and outpatient clinic. The organization offers risk assessments and appropriate screening tests; maintains computerized registries of affected individuals and those who may be at risk (e.g., for Familial Adenomatous Polyposis, Hereditary Nonpolyposis Colorectal Cancer, and Familial Colon Cancer). It suggests surveillance protocols and reviews surgical options for affected individuals. David G. Jagelman Inherited Colorectal Cancer Registries also
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provides a variety of educational and support materials including brochures, pamphlets, articles, and a newsletter called 'Family Matters.'. ·
Familial GI Cancer Registry Telephone: (416) 586-8334 Fax: (416) 586-8644 Email:
[email protected] Web Site: http://www.mtsinai.on.ca/familialgicancer Background: The Familial GI Cancer Registry is a professional and research center dedicated to providing professional services as well as emotional support to people affected by familial gastrointestinal cancer and their families. Established in 1980, the center conducts research studies and has an investigative team focused on innovative surgical techniques related to gastrointestinal cancer. The center also has a molecular diagnostic program and offers a screening service for family members who may be at risk for the hereditary form of the disease. Along with its scientific and medical departments, the center also has a genetic counseling department that offers advice and support to affected individuals and families. The Familial GI Cancer Registry maintains a database of affected individuals and produces educational and support materials including pamphlets, brochures, family guides, and a biannual newsletter. The Registry relays information regarding hospital and community resources through a patient library.
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Hereditary Colon Cancer Association (HCCA) Telephone: (605) 373-2067 Toll-free: (800) 264-6783 Fax: (605) 977-0647 Email:
[email protected] Web Site: http://www.hereditarycc.org Background: The Hereditary Colon Cancer Association (HCCA) provides information and support to patients who are at risk for inherited colon cancers. It also serves as a source of information to health professionals. It seeks to raise and distribute funds for research on the prevention of inherited colon cancers. An annual March Colorectal Cancer Awareness Campaign, two issues annually of the Prevention Advocate newsmagazine, and annual conference for both patients/families and medical professionals are the major yearly projects. With approximately 1800 members, the association was established in 1999.
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Hereditary Colorectal Cancer Registry Telephone: (410) 955-3875 Toll-free: (888) 772-6566 Fax: (410) 614-9544 Email:
[email protected] Web Site: http://www.coloncancer.org Background: This registry is operated through the Molecular Genetics Laboratory of Johns Hopkins Oncology Center. In addition to serving as the foundation for research on hereditary colorectal cancer at Johns Hopkins, the registry provides information on
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hereditary colorectal cancer to patients and their families, as well as to medical professionals. ·
International Cancer Alliance for Research and Education Telephone: (301) 654-7933 Toll-free: (800) 422-7361 Fax: (301) 654-8684 Email:
[email protected] Web Site: http://icare.org Background: The International Cancer Alliance for Research and Education (ICARE) is a nonprofit organization that provides focused information to individuals affected by cancer and their physicians on an ongoing, person-to-person basis. Cancer is a general term referring to a group of diseases characterized by uncontrolled cellular growth that may invade surrounding tissues and spread (metastasize) to other bodily tissues or organs. The different cancers may be classified based upon the organ and cell type involved, the nature of the malignancy, and the disease's clinical course. ICARE has developed several patient-centered programs through a process of collection, evaluation, and dissemination of information, bringing affected individuals into contact with physicians and scientists from around the world. The Alliance is operated by a network of scientists, clinicians, staff members, and lay volunteers, many of whom are affected by cancer themselves. The Alliance maintains the ICARE Registry, a confidential membership listing that permits ongoing dialogue between ICARE and its network members. Registry members receive a 'cancer therapy review' including a description of the specific form of cancer in question, information concerning detection and staging procedures, an overview of current treatments, a bibliography for more indepth research, and listings of diagnostic tests, ongoing clinical trials, and second opinion centers. Registry members also receive medical, research, clinical trial, and Food and Drug Administration (FDA) updates relating to the specific form of cancer or cancer in general; regular newsletters; and access to all ICARE programs. Such programs include ICARE patient education partner centers, which provide affected individuals with access to an electronic library of cancer information and online hook-ups at the community level; private electronic support groups for individuals dealing with common types of cancer or common issues; a clinical trial matching program; and other services. ICARE provides information concerning its mission, objectives, services, and programs on its web site on the Internet.
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Intestinal Multiple Polyposis and Colorectal Cancer Registry Telephone: (717) 788-3712 Fax: (717) 788-4046 Email:
[email protected] Background: The Intestinal Multiple Polyposis and Colorectal Cancer Registry, also known as IMPACC, is a not-for-profit self-help service organization that was established in 1986. The purpose of the group is to provide information and support to people affected by Multiple Polyposis or Hereditary Colorectal Cancer, their families, and their physicians. Multiple Familial Polyposis is a group of rare inherited conditions of the gastrointestinal system characterized by benign growths (adenomatous polyps) lining the mucous membrane of the intestine. Because such growths have high malignant potential, affected individuals may potentially develop cancer of the colon and/or rectum. The Registry promotes ongoing medical research into the causes, treatment, and
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prevention of these disorders. IMPACC also offers a variety of services including genetic counseling, referrals to appropriate avenues of treatment, and a quarterly newsletter. ·
Johns Hopkins Hereditary Colorectal Cancer Registry Telephone: (410) 955-3875 Toll-free: (888) 772-6566 Fax: (410) 614-9544 Email:
[email protected] Web Site: www.hopkikns.org Background: The Johns Hopkins Hereditary Colorectal Cancer Registry is a research organization that maintains a registry of families affected by different forms of Hereditary Colorectal Cancer including Hereditary Colon Cancer, Familial Adenomatous Polyposis, Hereditary Nonpolyposis Colorectal Cancer, Juvenile Polyposis, and Peutz-Jeghers Syndrome. Established in 1973, the Registry currently includes hundreds of families affected by these disorders. Interested individuals are offered the opportunity to participate in ongoing research studies. The Registry also offers educational materials to people affected by hereditary forms of colon cancer, their families, and physicians.
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M. D. Anderson Cancer Center Hereditary Colorectal Cancer Registry Telephone: (713) 792-2828 Toll-free: (800) 472-4376 Fax: (713) 745-1163 Email:
[email protected] Web Site: http://www.utmdacc.uth.tmc.edu/ Background: The University of Texas M.D. Anderson Cancer Center Hereditary Colorectal Cancer Registry is a registry organization dedicated to evaluating families in which there is a suspected or confirmed risk of a hereditary colorectal cancer syndrome. Established in 1988, the registry stafRegistry's staff makes arrangements to obtain necessary risk assessment, tests, procedures, or treatments at M.D. Anderson. Genetic testing and counseling are performed on appropriate families in order to identify persons at high risk for hereditary colorectal cancer. Individuals and their family members can also be evaluated for eligibility for other ongoing studies such as chemoprevention and psychosocial studies. Educational materials include a periodic newsletter entitled 'Hereditary Colon Cancer Newsletter,' a guide entitled 'Johns Hopkins Guide for Patients and Families: Familial Adenomatous Polyposis (FAP),' and 'Hereditary Non-Polyposis Colon Cancer: A Guide for Patients and Families.' Program activities include genetic counseling, educational programs, and referrals.
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Ovarian Cancer National Alliance Telephone: (202) 331-1332 Fax: (202) 293-1990 Email:
[email protected] Web Site: http://www.ovariancancer.org Background: The Ovarian Cancer National Alliance is a voluntary not-for-profit umbrella organization uniting ovarian cancer survivors, women's health activists, and health care professionals in a coordinated effort to focus national attention on ovarian
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cancer. The symptoms of ovarian cancer are often subtle and may be easily confused with symptoms associated with other disorders. Such symptoms commonly include pressure or bloating in the abdomen, constant and progressive changes in bladder or bowel patterns, persistent digestive problems, ongoing excessive fatigue, abnormal bleeding, and pain during intercourse. The Ovarian Cancer National Alliance, which was established in 1997, works to fight ovarian cancer by focusing on four key areas: expanding women's and health care providers' awareness about the disease; advocating for increased funding for research, sound genetic-testing policies, and insurance coverage of therapies; furthering the scientific understanding of ovarian cancer to improve screening and detection tools and to discover a cure; and coordinating efforts in the fight against ovarian cancer by developing networks among ovarian cancer groups and activists and other health advocates. The Alliance's activities include providing expert testimony before government committees, serving as consumer representatives on federal panels that set priorities for ovarian cancer research, working closely with the Society of Gynecologic Oncologists to strengthen ovarian cancer resources, and conducting national advocacy conferences for the ovarian cancer community. The Alliance also has a web site on the Internet and provides a variety of educational materials including brochures, the 'Ovarian Cancer National Resource List,' 'Facts about Ovarian Cancer,' and a regular newsletter. ·
PMP Pals Network Telephone: (831) 424-4545 Fax: (831) 424-4545 Email:
[email protected] Web Site: http://www.pmppals.org Background: PMP (Pseudomyxoma Peritonei) Pals is a self-help organization dedicated to providing information, support, and resources to individuals with pseudomyxoma peritonei and their family members. Pseudomyxoma Peritonei is a rare malignancy characterized by the progressive accumulation of mucus-secreting (mucinous) tumor cells within the abdomen and pelvis. PMP develops after a small growth (polyp) located within the appendix bursts through the wall of the appendix and spreads mucusproducing tumor cells throughout surrounding surfaces (e.g., the membrane lining the abdominal cavity [peritoneum]). As mucinous tumor cells accumulate, the abdominal area becomes swollen and digestive function becomes impaired. PMP Pals was established in 1998 and currently consists of approximately 650 members. The organization provides information concerning oncologists and surgeons who are experienced in treating PMP; promotes and support research; offers information on additional services for individuals with cancer; and promotes networking opportunities, enabling affected individuals and family members to select various 'PMP Pals' networking categories (e.g., Mothers with PMP, Female PMP Patients, Male PMP Patients, Seniors with PMP, Spouses of PMP Patients, etc.). PMP Pals also publishes a regular newsletter entitled 'PMP Pals: Support for Pseudomyxoma Peritonei Patients.'.
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Roswell Park Family Cancer Registry Telephone: (716) 845-5815 Toll-free: (800) 685-6825 Fax: (716) 845-8980 Email:
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Background: Roswell Park Family Cancer Registry is a research organization dedicated to registering families at risk of developing cancers. The Registry seeks to educate affected individuals and family members in the areas of prevention, early detection, and treatment of cancer, as well as risk assessment of such family members. Established in 1992, this research program is designed to obtain detailed medical and family history information from people who, because of their family history or other risk factors, may have an increased potential of developing cancer. To this end, the Registry takes blood and other tissue samples. This material is provided to research scientists studying cancer genes. The affected individuals or families are thus provided with updated information on genetics, genetic cancers, and testing. The Registry produces educational materials including a pamphlet entitled 'Hereditary Non-polyposis Colorectal Cancer.' The organization supports such program activities as genetic counseling, patient and general education, and research. ·
Strang-Cornell Hereditary Colon Cancer Program Telephone: (212) 746-5656 Fax: (212) 746-8765 Email:
[email protected] Web Site: http://www.strang.org Background: The Strang-Cornell Hereditary Colon Cancer Program (SCPC) is a not-forprofit organization dedicated to providing individuals with Familial Adenomatous Polyposis (FAP) and Hereditary Nonpolyposis Colorectal Cancer (HNPCC) clinical and educational services, as well as to foster participation in research. Colorectal cancer is a common disease in the United States. While most cases of colorectal cancer are sporadic, up to ten percent are hereditary. Hereditary colorectal cancer includes the polyposis syndromes, of which Familial Adenomatious Polyposis is the most common, and the nonpolyposis syndromes, broadly referred to as Hereditary Nonpolyposis Colorectal Cancer. Established in 1934, this program is a collaboration between the Strang Cancer Prevention Center and the New York Hospital-Cornell Medical Center. SCPC includes three divisions: registries for FAP and HNPCC, clinical and pre-clinical research, and clinical services.
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to colon cancer. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with colon cancer.
The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about colon cancer. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797.
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Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “colon cancer” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “colon cancer”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “colon cancer” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “colon cancer” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.26
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
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Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)27: ·
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
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Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries 475
·
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
477
ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: ·
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on colon cancer: ·
Basic Guidelines for Colon Cancer Colon cancer Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000262.htm Colon cancer screening Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002071.htm
·
Signs & Symptoms for Colon Cancer Abdominal fullness, gaseous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003124.htm Abdominal pain and tenderness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003120.htm Anemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000560.htm
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Blood in the stool Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003130.htm Constipation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003125.htm Diarrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003126.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Tiredness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Weight loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003107.htm ·
Diagnostics and Tests for Colon Cancer Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Colonoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003886.htm Fecal Occult Blood Test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003393.htm Sigmoidoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003885.htm Stool guaiac Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003393.htm
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Nutrition for Colon Cancer High-fat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002468.htm
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Background Topics for Colon Cancer Cancer - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002166.htm Chemotherapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002324.htm Metastasis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002260.htm
Online Glossaries 479
Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm Radiation therapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001918.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: ·
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
·
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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COLON CANCER DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1,2-Dimethylhydrazine: A DNA alkylating agent that has been shown to be a potent carcinogen and is widely used to induce colon tumors in experimental animals. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH]
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Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenomatous Polyposis Coli: An autosomal dominant polyposis syndrome in which the colon contains few to thousands of adenomatous polyps, often occurring by age 15 to 25. [NIH]
Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]
Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Age-Adjusted: Summary measures of rates of morbidity or mortality in a population using statistical procedures to remove the effect of age differences in populations that are being compared. Age is probably the most important and the most common variable in determining the risk of morbidity and mortality. [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH]
Dictionary 483
Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] Agonists: Drugs that trigger an action from a cell or another drug. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Alfalfa: A deep-rooted European leguminous plant (Medicago sativa) widely grown for hay and forage. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]
Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation
484 Colon Cancer
of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Anal Fissure: A small tear in the anus that may cause itching, pain, or bleeding. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphase: The third phase of cell division, in which the chromatids separate and migrate to opposite poles of the spindle. [NIH] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anchorage: In dentistry, points of retention of fillings and artificial restorations and appliances. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy
Dictionary 485
(symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] Angina: Chest pain that originates in the heart. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Angioma: A tumor composed of lymphatic or blood vessels. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Anoikis: Apoptosis triggered by loss of contact with the extracellular matrix. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antiangiogenic: Having to do with reducing the growth of new blood vessels. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody therapy: Treatment with an antibody, a substance that can directly kill specific tumor cells or stimulate the immune system to kill tumor cells. [NIH] Anticarcinogenic: cancer. [NIH]
Pertaining to something that prevents or delays the development of
Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood
486 Colon Cancer
thinner. [NIH] Anticonvulsants: Drugs used to prevent seizures or reduce their severity. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimetastatic: Having to do with reducing inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastons: Substances isolated from normal human blood and urine being tested as a type of treatment for some tumors and AIDS. [NIH] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antitumour: Counteracting tumour formation. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Appendicitis: Acute inflammation of the vermiform appendix. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Approximate: Approximal [EU]
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Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH] Ascending Colon: The part of the colon on the right side of the abdomen. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Azoxymethane: A potent carcinogen and neurotoxic compound. It is particularly effective in inducing colon carcinomas. [NIH] Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the thoracic, lumbar, sacral, or adjacent regions. [NIH] Bacteremia:
The presence of viable bacteria circulating in the blood. Fever, chills,
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tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial toxin: A toxic substance, made by bacteria, that can be modified to kill specific tumor cells without harming normal cells. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous. [NIH] Barium enema: A procedure in which a liquid with barium in it is put into the rectum and colon by way of the anus. Barium is a silver-white metallic compound that helps to show the image of the lower gastrointestinal tract on an x-ray. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Berberine: An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal. [NIH] Beta-Glucosidase: An enzyme that catalyzes the hydrolysis of terminal non-reducing residues in beta-D-glucosides with release of beta-glucose. EC 3.2.1.21. [NIH]
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Bevacizumab: A monoclonal antibody that may prevent the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH]
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Bladder: The organ that stores urine. [NIH] Blastomyces: A genus of onygenacetous mitosporic fungi whose perfect state is Ajellomyces. The species Blastomyces dermatitidis (perfect state Ajellomyces dermatitidis) causes blastomycosis. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bowel Prep: The process used to clean the colon with enemas and a special drink. Used before surgery of the colon, colonoscopy, or barium x-ray. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH]
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Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Caloric intake: Refers to the number of calories (energy content) consumed. [NIH] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] Cancer vaccine: A vaccine designed to prevent or treat cancer. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the respone to colon cancer treatment. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoid: A type of tumor usually found in the gastrointestinal system (most often in the appendix), and sometimes in the lungs or other sites. Carcinoid tumors are usually benign.
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[NIH]
Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Caspase 1: A member of the caspase family that is highly specific for interleukin-1beta (interleukin-1). It plays a role in inflammation and mammalian apoptosis. Interleukin-1beta converting enzyme is frequently abbreviated ICE. EC 3.4.22.36 [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] CDC2: It is crucial for entry into mitosis of eukaryotic cells. [NIH] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH]
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Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells. [NIH] Cell motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central retinal vein: The blood vessel that carries blood from the retina. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere
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that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Checkup: A general physical examination. [NIH] Chemoembolization: A procedure in which the blood supply to the tumor is blocked surgically or mechanically, and anticancer drugs are administered directly into the tumor. This permits a higher concentration of drug to be in contact with the tumor for a longer period of time. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemoprotective: A quality of some drugs used in cancer treatment. Chemoprotective agents protect healthy tissue from the toxic effects of anticancer drugs. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [NIH]
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Choleretic: A choleretic agent. [EU] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Choline Kinase: An enzyme that is active in the first step of choline phosphoglyceride (lecithin) biosynthesis by catalyzing the phosphorylation of choline to phosphorylcholine in the presence of ATP. Ethanolamine and its methyl and ethyl derivatives can also act as acceptors. EC 2.7.1.32. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by
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physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Colectomy: An operation to remove the colon. An open colectomy is the removal of the colon through a surgical incision made in the wall of the abdomen. Laparoscopic-assisted colectomy uses a thin, lighted tube attached to a video camera. It allows the surgeon to remove the colon without a large incision. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colon Polyps: Small, fleshy, mushroom-shaped growths in the colon. [NIH] Colonic Polyps: Pedunculated or sessile growths arising from the mucous membrane of the colon. [NIH] Colonoscope: A thin, lighted tube used to examine the inside of the colon. [NIH] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Colorectal Neoplasms: Tumors or cancer of the either the colon or rectum or both. The
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most frequent malignant tumor in the United States. Etiological factors which increase the risk of colorectal cancer include chronic ulcerative colitis, familial polyposis of the colon, exposure to asbestos, irradiation of the cervix. [NIH] Colostomy: An opening into the colon from the outside of the body. A colostomy provides a new path for waste material to leave the body after part of the colon has been removed. [NIH]
Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make
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biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomographic colonography: CTC. A procedure in which a detailed picture of the colon is created by an x-ray machine linked to a computer. Also called computed tomography (CT) scan or computerized axial tomography (CAT) scan of the colon. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Conscious Sedation: An alternative to general anesthesia in patients for whom general anesthesia is refused or considered inadvisable. It involves the administering of an antianxiety drug (minor tranquilizer) and an analgesic or local anesthetic. This renders the patient free of anxiety and pain while allowing the patient to remain in verbal contact with the physician or dentist. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU]
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Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: group. [NIH]
An experiment or clinical trial that includes a comparison (control)
Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vessels: The veins and arteries of the heart. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cost-benefit: A quantitative technique of economic analysis which, when applied to radiation practice, compares the health detriment from the radiation doses concerned with the cost of radiation dose reduction in that practice. [NIH] Cost-Benefit Analysis: A method of comparing the cost of a program with its expected benefits in dollars (or other currency). The benefit-to-cost ratio is a measure of total return expected per unit of money spent. This analysis generally excludes consideration of factors that are not measured ultimately in economic terms. Cost effectiveness compares alternative ways to achieve a specific set of results. [NIH] Criterion: A standard by which something may be judged. [EU] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cryosurgery: The use of freezing as a special surgical technique to destroy or excise tissue. [NIH]
Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to
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which a subject has learned to respond. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curcumin: A dye obtained from tumeric, the powdered root of Curcuma longa Linn. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, ... New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
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Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH]
Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Deoxycholic Acid: A bile acid formed by bacterial action from cholate. It is usually conjugated with glycine or taurine. Deoxycholic acid acts as a detergent to solubilize fats for intestinal absorption, is reabsorbed itself, and is used as a choleretic and detergent. [NIH] Deoxyguanosine: A nucleoside consisting of the base guanine and the sugar deoxyribose. [NIH]
Deoxyuridine: 2'-Deoxyuridine. An antimetabolite that is converted to deoxyuridine triphosphate during DNA synthesis. Laboratory suppression of deoxyuridine is used to diagnose megaloblastic anemias due to vitamin B12 and folate deficiencies. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Descending Colon: The part of the colon where stool is stored. Located on the left side of the abdomen. [NIH] Desmoid tumor: A tumor of the tissue that surrounds muscles, usually in the abdomen. Desmoid tumors rarely metastasize. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or
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esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialysate: A cleansing liquid used in the two major forms of dialysis--hemodialysis and peritoneal dialysis. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Dietary Fiber: The remnants of plant cell walls that are resistant to digestion by the alimentary enzymes of man. It comprises various polysaccharides and lignins. [NIH] Diethylcarbamazine: An anthelmintic used primarily as the citrate in the treatment of filariasis, particularly infestations with Wucheria bancrofti or Loa loa. [NIH] Difluoromethylornithine: DFMO. An anticancer drug that has been shown to reduce the risk of cancer in animals. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Digital rectal examination: DRE. An examination in which a doctor inserts a lubricated, gloved finger into the rectum to feel for abnormalities. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Dissection: Cutting up of an organism for study. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Distention: The state of being distended or enlarged; the act of distending. [EU] Diverticula: Plural form of diverticulum. [NIH] Diverticulitis: Inflammation of a diverticulum or diverticula. [NIH] Diverticulosis: A condition marked by small sacs or pouches (diverticula) in the walls of an organ such as the stomach or colon. These sacs can become inflamed and cause a condition called diverticulitis, which may be a risk factor for certain types of cancer. [NIH] Diverticulum: A pathological condition manifested as a pouch or sac opening from a tubular or sacular organ. [NIH] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of singlestranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted
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rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dwell time: In peritoneal dialysis, the amount of time a bag of dialysate remains in the patient's abdominal cavity during an exchange. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Edrecolomab: A type of monoclonal antibody used in cancer detection or therapy. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and
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hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Ellagic Acid: A fused four ring compound occurring free or combined in galls. Isolated from the kino of Eucalyptus maculata Hook and E. Hemipholia F. Muell. Activates Factor XII of the blood clotting system which also causes kinin release; used in research and as a dye. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Emollient: Softening or soothing; called also malactic. [EU] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH]
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Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enema: The injection of a liquid through the anus into the large bowel. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Energy Intake: Total number of calories taken in daily whether ingested or by parenteral routes. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enterohepatic: Of or involving the intestine and liver. [EU] Enterohepatic Circulation: Recycling through liver by excretion in bile, reabsorption from intestines into portal circulation, passage back into liver, and re-excretion in bile. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]
Enterotoxins: Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc.; most common enterotoxins are produced by bacteria. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH] Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH]
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Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU]
Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermal growth factor receptor: EGFR. The protein found on the surface of some cells and to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of cancer cells, so these cells may divide excessively in the presence of epidermal growth factor. Also known as ErbB1 or HER1. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]
Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Escherichia: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria whose organisms occur in the lower part of the intestine of warm-blooded animals. The species are either nonpathogenic or opportunistic pathogens. [NIH] Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce diarrhea and pyogenic infections.
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[NIH]
Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Exhaustion: The feeling of weariness of mind and body. [NIH] Exisulind: A drug that is being studied in the treatment and prevention of cancer. It has been shown to cause apoptosis (cell death) in cancerous and precancerous cells by acting through a group of cellular enzymes called cGMP phosphodiesterases. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expert Testimony: Presentation of pertinent data by one with special skill or knowledge representing mastery of a particular subject. [NIH] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH]
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Faecal: Pertaining to or of the nature of feces. [EU] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [NIH] False Positive Reactions: Area that the program rates as suspicious but that the radiologist ultimately decides does not represent a possible malignancy. [NIH] Familial polyposis: An inherited condition in which numerous polyps (tissue masses) develop on the inside walls of the colon and rectum. It increases the risk for colon cancer. [NIH]
Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Farnesyl: Enzyme which adds 15 carbon atoms to the Ras precursor protein. [NIH] Fat: Total lipids including phospholipids. [NIH] Fathers: Male parents, human or animal. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fecal Incontinence: Failure of voluntary control of the anal sphincters, with involuntary passage of feces and flatus. [NIH] Fecal occult blood test: A test to check for blood in stool. (Fecal refers to stool; occult means hidden.) [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ,
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usually as a consequence of inflammation or other injury. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Flavopiridol: Belongs to the family of anticancer drugs called flavinols. [NIH] Floxuridine: An antineoplastic antimetabolite that is metabolized to fluorouracil when administered by rapid injection; when administered by slow, continuous, intra-arterial infusion, it is converted to floxuridine monophosphate. It has been used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follicular large cell lymphoma: A rare type of non- Hodgkin's lymphoma (cancer of the lymphatic system) with large cells that look cleaved (split) or non-cleaved under the microscope. It is an indolent (slow-growing) type of lymphoma. [NIH] Forearm: The part between the elbow and the wrist. [NIH]
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Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Fructans: Polysaccharides composed of D-fructose units. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Gamma-interferon: Interferon produced by T-lymphocytes in response to various mitogens and antigens. Gamma interferon appears to have potent antineoplastic, immunoregulatory and antiviral activity. [NIH] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglioside: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [NIH]
Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]
Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid.
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[NIH]
Gastrin-Releasing Peptide: Neuropeptide and gut hormone that helps regulate gastric acid secretion and motor function. Once released from nerves in the antrum of the stomach, the neuropeptide stimulates release of gastrin from the G cells. [NIH] Gastroenterologist: A doctor who specializes in diagnosing and treating disorders of the digestive system. [NIH] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gemcitabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]
Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Amplification: A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development. [NIH] Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH]
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Gene-modified: Cells that have been altered to contain different genetic material than they originally contained. [NIH] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ-free: Free of bacteria, disease-causing viruses, and other organisms that can cause infection. [NIH] Germline mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; germline mutations are passed on from parents to offspring. Also called hereditary mutation. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH]
Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen
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frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycogen Synthase: An enzyme that catalyzes the transfer of D-glucose from UDPglucose into 1,4-alpha-D-glucosyl chains. EC 2.4.1.11. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH]
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Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granulocyte-Macrophage Colony-Stimulating Factor: An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Group Practice: Any group of three or more full-time physicians organized in a legally recognized entity for the provision of health care services, sharing space, equipment, personnel and records for both patient care and business management, and who have a predetermined arrangement for the distribution of income. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Growth Inhibitors: Endogenous or exogenous substances which inhibit the normal growth of human and animal cells or micro-organisms, as distinguished from those affecting plant growth (plant growth regulators). [NIH] Guanine: One of the four DNA bases. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Gynecologic cancer: Cancer of the female reproductive tract, including the cervix, endometrium, fallopian tubes, ovaries, uterus, and vagina. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Hawaii: A group of islands in Polynesia, in the north central Pacific Ocean, comprising eight major and 114 minor islands, largely volcanic and coral. Its capital is Honolulu. It was first reached by Polynesians about 500 A.D. It was discovered and named the Sandwich Islands in 1778 by Captain Cook. The islands were united under the rule of King Kamehameha 1795-1819 and requested annexation to the United States in 1893 when a provisional government was set up. Hawaii was established as a territory in 1900 and admitted as a state in 1959. The name is from the Polynesian Owhyhii, place of the gods, with reference to the two volcanoes Mauna Kea and Mauna Loa, regarded as the abode of the gods. (From Webster's New Geographical Dictionary, 1988, p493 & Room, Brewer's Dictionary of Names, 1992, p2330 [NIH]
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Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Policy: Decisions, usually developed by government policymakers, for determining present and future objectives pertaining to the health care system. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hematogenous: Originating in the blood or spread through the bloodstream. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhoids: Varicosities of the hemorrhoidal venous plexuses. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH]
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Hepatocyte: A liver cell. [NIH] Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is proto-oncogene protein C-met. [NIH] Hepatoma: A liver tumor. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Hereditary mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; hereditary mutations are passed on from parents to offspring. Also called germline mutation. [NIH] Hereditary nonpolyposis colon cancer: An inherited disorder in which affected individuals have a higher-than-normal chance of developing colon cancer and certain other types of cancer, usually before the age of 60. Also called Lynch syndrome. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hernia: Protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [NIH]
Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH] Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeobox: Distinctive sequence of DNA bases. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homeotic: Characterizes genes the mutations of which lead to inappropriate expressions of characteristics normally associated with another part of the organism (homeotic mutants). [NIH]
Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]
Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homotypic: Adhesion between neutrophils. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU]
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Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH]
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Hypnotic: A drug that acts to induce sleep. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiotype: The unique antigenic determinant in the variable region. [NIH] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileostomy: Surgical creation of an external opening into the ileum for fecal diversion or drainage. Loop or tube procedures are most often employed. [NIH] Ileum: The lower end of the small intestine. [NIH] Ileus: Obstruction of the intestines. [EU] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: (antigens). [NIH]
The activity of the immune system against foreign substances
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic effects of foreign microorganisms or to the toxic effect of antigenic substances. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Immunotoxin: An antibody linked to a toxic substance. Some immmunotoxins can bind to cancer cells and kill them. [NIH]
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Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU]
Indolent: A type of cancer that grows slowly. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infiltrating cancer: Cancer that has spread beyond the layer of tissue in which it developed and is growing into surrounding, healthy tissues. Also called invasive cancer. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease.
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[NIH]
Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insufflation: The act of blowing a powder, vapor, or gas into any body cavity for experimental, diagnostic, or therapeutic purposes. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Insulin-Like Growth Factor Binding Protein 3: One of the six homologous soluble proteins that bind insulin-like growth factors (somatomedins) and modulate their mitogenic and metabolic actions at the cellular level. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon Alfa-2a: A recombinant alfa interferon consisting of 165 amino acids with lysine at position 23 and histidine at position 34. It is used extensively as an antiviral and antineoplastic agent. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interferon-beta: One of the type I interferons produced by fibroblasts in response to stimulation by live or inactivated virus or by double-stranded RNA. It is a cytokine with
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antiviral, antiproliferative, and immunomodulating activity. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-10: Factor that is a coregulator of mast cell growth. It is produced by T-cells and B-cells and shows extensive homology with the Epstein-Barr virus BCRFI gene. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Flora: The bacteria, yeasts, and fungi that grow normally in the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH]
Intestinal Polyps: Pedunculated or sessile growths arising from the intestinal mucosa and extending into the lumen. The disease includes intestinal polyposis. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [NIH] Intrahepatic: Within the liver. [NIH] Intraperitoneal: organs). [NIH]
IP. Within the peritoneal cavity (the area that contains the abdominal
Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
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Invasive cancer: Cancer that has spread beyond the layer of tissue in which it developed and is growing into surrounding, healthy tissues. Also called infiltrating cancer. [NIH] Invasive cervical cancer: Cancer that has spread from the surface of the cervix to tissue deeper in the cervix or to other parts of the body. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irinotecan: An anticancer drug that belongs to a family of anticancer drugs called topoisomerase inhibitors. It is a camptothecin analogue. Also called CPT 11. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irrigation: The washing of a body cavity or surface by flowing solution which is inserted and then removed. Any drug in the irrigation solution may be absorbed. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isothiocyanates: Organic compounds with the general formula R-NCS. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]
Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Karyotype: The characteristic chromosome complement of an individual, race, or species as defined by their number, size, shape, etc. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Killer Cells: Lymphocyte-like effector cells which mediate antibody-dependent cell cytotoxicity. They kill antibody-coated target cells which they bind with their Fc receptors. [NIH]
Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement
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membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Laparoscopic-assisted colectomy: Surgery done with the aid of a laparoscope (a thin, lighted tube) to remove part or all of the colon through small incisions made in the wall of the abdomen. [NIH] Laparotomy: A surgical incision made in the wall of the abdomen. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Leucovorin: The active metabolite of folic acid. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levamisole: An antiparasitic drug that is also being studied in cancer therapy with fluorouracil. [NIH] Library Services: circulation. [NIH]
Services offered to the library user. They include reference and
Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH]
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Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH] Lithocholic Acid: A bile acid formed from chenodeoxycholate by bacterial action, usually conjugated with glycine or taurine. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as cholagogue and choleretic. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver metastases: Cancer that has spread from the original (primary) tumor to the liver. [NIH]
Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locoregional: The characteristic of a disease-producing organism to transfer itself, but typically to the same region of the body (a leg, the lungs, ...) [EU] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Lomustine: An alkylating agent of value against both hematologic malignancies and solid tumors. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl
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coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]
Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymph node mapping: The use of dyes and radioactive substances to identify lymph nodes that contain tumor cells. [NIH] Lymphadenectomy: A surgical procedure in which the lymph nodes are removed and examined to see whether they contain cancer. Also called lymph node dissection. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokine: A soluble protein produced by some types of white blood cell that stimulates other white blood cells to kill foreign invaders. [NIH] Lymphokine-activated killer cells: White blood cells that are stimulated in a laboratory to kill tumor cells. Also called LAK cells. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH]
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Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammography: Radiographic examination of the breast. [NIH] Mass Screening: Organized periodic procedures performed on large groups of people for the purpose of detecting disease. [NIH] Matrilysin: The smallest member of the matrix metalloproteinases. It plays a role in tumor progression. EC 3.4.24.23. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]
Meat Products: Articles of food which are derived by a process of manufacture from any portion of carcasses of any animal used for food (e.g., head cheese, sausage, scrapple). [NIH] Meconium: The thick green-to-black mucilaginous material found in the intestines of a fullterm fetus. It consists of secretions of the intestinal glands, bile pigments, fatty acids, amniotic fluid, and intrauterine debris. It constitutes the first stools passed by a newborn. [NIH]
Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: illnesses. [NIH]
Recording of pertinent information concerning patient's illness or
Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medically Uninsured:
Individuals or groups with no or inadequate health insurance
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coverage. Those falling into this category usually comprise three primary groups: the medically indigent, those whose clinical condition makes them medically uninsurable, and the working uninsured. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megacolon: Pathological enlargement of the colon. [NIH] Megaloblastic: anaemia. [EU]
A large abnormal red blood cell appearing in the blood in pernicious
Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melanosis: Disorders of increased melanin pigmentation that develop without preceding inflammatory disease. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Menarche: The establishment or beginning of the menstrual function. [EU] Meningeal: Refers to the meninges, the tissue covering the brain and spinal cord. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to
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the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastasize: To spread from one part of the body to another. When cancer cells metastasize and form secondary tumors, the cells in the metastatic tumor are like those in the original (primary) tumor. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Metastatic cancer: Cancer that has spread from the place in which it started to other parts of the body. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Micronutrients: Essential dietary elements or organic compounds that are required in only small quantities for normal physiologic processes to occur. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microspheres: Small uniformly-sized spherical particles frequently labeled with radioisotopes or various reagents acting as tags or markers. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH]
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Milk Thistle: The plant Silybum marianum in the family Asteraceae containing the bioflavonoid complex silymarin. For centuries this has been used traditionally to treat liver disease. [NIH] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mistletoe lectin: A substance that comes from the mistletoe plant, and that is being studied as a treatment for cancer. A lectin is a complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitomycin: An antineoplastic antibiotic produced by Streptomyces caespitosus. It acts as a bi- or trifunctional alkylating agent causing cross-linking of DNA and inhibition of DNA synthesis. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH]
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Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]
Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucilaginous: Pertaining to or secreting mucus. [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucinous Adenocarcinoma: A malignant tumor of the epithelial cells of a gland which typically metastasizes by way of the lymphatics. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]
Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagenicity: Ability to damage DNA, the genetic material; the power to cause mutations. [NIH]
Mutate: To change the genetic material of a cell. Then changes (mutations) can be harmful,
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beneficial, or have no effect. [NIH] Mycosis: Any disease caused by a fungus. [EU] Myelodysplastic syndrome: Disease in which the bone marrow does not function normally. Also called preleukemia or smoldering leukemia. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myelosuppression: A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of some cancer treatments. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] N-acetyl: Analgesic agent. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuraminidase: An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in
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oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992) EC 3.2.1.18. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Node-negative: Cancer that has not spread to the lymph nodes. [NIH] Node-positive: Cancer that has spread to the lymph nodes. [NIH] Nonmalignant: Not cancerous. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Matrix: The fibrogranular network of residual structural elements within which are immersed both chromatin and ribonucleoproteins. It extends throughout the nuclear interior
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from the nucleolus to the nuclear pore complexes along the nuclear periphery. [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia. [NIH] Nurse Practitioners: Nurses who are specially trained to assume an expanded role in providing medical care under the supervision of a physician. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Occult Bleeding: Blood in stool that is not visible to the naked eye. May be a sign of disease such as diverticulosis or colorectal cancer. [NIH] Occult Blood: Chemical, spectroscopic, or microscopic detection of extremely small amounts of blood. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH]
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Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH]
Oncology: The study of cancer. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Organ Specificity: Restriction of a characteristic or response to a particular organ of the body; it usually refers to that property of the immune response which differentiates one organ from another on the basis of antigen recognition, but the concept is not limited to immunology. [NIH] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ostomy: Surgical construction of an artificial opening (stoma) for external fistulization of a duct or vessel by insertion of a tube with or without a supportive stent. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovarian Cysts: General term for cysts and cystic diseases of the ovary. [NIH] Ovarian epithelial cancer: Cancer that occurs in the cells lining the ovaries. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overall survival: The percentage of subjects in a study who have survived for a defined period of time. Usually reported as time since diagnosis or treatment. Often called the survival rate. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxaliplatin: An anticancer drug that belongs to the family of drugs called platinum compounds. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress,
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1991, pxv-xvi). [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palliative therapy: Treatment given to relieve symptoms caused by advanced cancer. Palliative therapy does not alter the course of a disease but improves the quality of life. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Pancreaticoduodenectomy: The excision of the head of the pancreas and the encircling loop of the duodenum to which it is connected. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Papovaviridae: A family of small, non-enveloped DNA viruses affecting mostly mammals. Most members can induce tumors in hosts. There are two genera: Papillomavirus and Polyomavirus. [NIH] Paracoccidioidomycosis: A mycosis affecting the skin, mucous membranes, lymph nodes, and internal organs. It is caused by Paracoccidioides brasiliensis. It is also called paracoccidioidal granuloma. Superficial resemblance of P. brasiliensis to Blastomyces brasiliensis (blastomyces) may cause misdiagnosis. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU]
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Partnership Practice: A voluntary contract between two or more doctors who may or may not share responsibility for the care of patients, with proportional sharing of profits and losses. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Compliance: regimen. [NIH]
Voluntary cooperation of the patient in following a prescribed
Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
PDQ: Physician Data Query. PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information is available on the CancerNet Web site, and more specific information about PDQ can be found at http://cancernet.nci.nih.gov/pdq.html. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Pentoxifylline: A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perceived risk: Estimate or evaluation of risk as observed through personal experience or personal study, and personal evaluation of consequences. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH]
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Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Periodicity: The tendency of a phenomenon to recur at regular intervals; in biological systems, the recurrence of certain activities (including hormonal, cellular, neural) may be annual, seasonal, monthly, daily, or more frequently (ultradian). [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral stem cell transplantation: A method of replacing blood-forming cells destroyed by cancer treatment. Immature blood cells (stem cells) in the circulating blood that are similar to those in the bone marrow are given after treatment to help the bone marrow recover and continue producing healthy blood cells. Transplantation may be autologous (an individual's own blood cells saved earlier), allogeneic (blood cells donated by someone else), or syngeneic (blood cells donated by an identical twin). Also called peripheral stem cell support. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH]
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Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenylbutyrate: An anticancer drug that belongs to the family of drugs called differentiating agents. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Phosphorylcholine: Calcium and magnesium salts used therapeutically in hepatobiliary dysfunction. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photosensitization: The development of abnormally heightened reactivity of the skin to sunlight. [EU] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Fitness: A state of well-being in which performance is optimal, often as a result of physical conditioning which may be prescribed for disease therapy. [NIH] Physician Assistants: Persons academically trained, licensed, or credentialed to provide medical care under the supervision of a physician. The concept does not include nurses, but does include orthopedic assistants, surgeon's assistants, and assistants to other specialists. [NIH]
Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]
Pilot study: The initial study examining a new method or treatment. [NIH]
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Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plant Components: The anatomical components of a plant, including seeds. [NIH] Plant Growth Regulators: Any of the hormones produced naturally in plants and active in controlling growth and other functions. There are three primary classes: auxins, cytokinins, and gibberellins. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Platinum Compounds: Inorganic compounds which contain platinum as the central atom. [NIH]
Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the
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size and shape of cells or their nuclei. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]
Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polyomavirus: A genus of the family papovaviridae consisting of potentially oncogenic viruses normally present in the host as a latent infection. The virus is oncogenic in hosts different from the species of origin. [NIH] Polyp: A growth that protrudes from a mucous membrane. [NIH] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of cirrhosis. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Positron emission tomography scan: PET scan. A computerized image of the metabolic activity of body tissues used to determine the presence of disease. [NIH]
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Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precancerous polyps: Growths that protrude from a mucous membrane. Precancerous polyps may (or are likely to) become cancer. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Preleukemia: Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria. [NIH] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Preoperative: Preceding an operation. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Preventive Health Services: Services designed for promotion of health and prevention of
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disease. [NIH] Preventive Medicine: A medical specialty primarily concerned with prevention of disease and the promotion and preservation of health in the individual. [NIH] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Primary Sclerosing Cholangitis: Irritation, scarring, and narrowing of the bile ducts inside and outside the liver. Bile builds up in the liver and may damage its cells. Many people with this condition also have ulcerative colitis. [NIH] Primary tumor: The original tumor. [NIH] Private Practice: Practice of a health profession by an individual, offering services on a person-to-person basis, as opposed to group or partnership practice. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Proctitis: Inflammation of the rectum. [EU] Proctocolectomy: An operation to remove the colon and rectum. Also called coloproctectomy. [NIH] Proctoscopy: Endoscopic examination, therapy or surgery of the rectum. [NIH] Proctosigmoidoscopy: An examination of the rectum and the lower part of the colon using a thin, lighted tube called a sigmoidoscope. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Program Evaluation: Studies designed to assess the efficacy of programs. They may include the evaluation of cost-effectiveness, the extent to which objectives are met, or impact. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed
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over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH]
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Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Proto-Oncogenes: Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Protooncogenes have names of the form c-onc. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Proxy: A person authorized to decide or act for another person, for example, a person having durable power of attorney. [NIH] Pseudomembranous Colitis: Severe irritation of the colon. Caused by Clostridium difficile bacteria. Occurs after taking oral antibiotics, which kill bacteria that normally live in the colon. [NIH] Pseudomyxoma peritonei: A build-up of mucus in the peritoneal cavity. The mucus may come from ruptured ovarian cysts, the appendix, or from other abdominal tissues, and mucus-secreting cells may attach to the peritoneal lining and continue to secrete mucus. [NIH]
Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psyllium: Dried, ripe seeds of Plantago psyllium, P. indica, and P. ovata (Plantaginaceae). Plantain seeds swell in water and are used as demulcents and bulk laxatives. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH]
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Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Purgative: 1. Cathartic (def. 1); causing evacuation of the bowels. 2. A cathartic, particularly one that stimulates peristaltic action. [EU] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [NIH] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioactivity: The quality of emitting or the emission of corpuscular or electromagnetic radiations consequent to nuclear disintegration, a natural property of all chemical elements of atomic number above 83, and possible of induction in all other known elements. [EU] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH]
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Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiologist: A doctor who specializes in creating and interpreting pictures of areas inside the body. The pictures are produced with x-rays, sound waves, or other types of energy. [NIH]
Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiosensitization: The use of a drug that makes tumor cells more sensitive to radiation therapy. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [NIH] Raltitrexed: An anticancer drug that inhibits tumor cells from multiplying by interfering with cells' ability to make DNA. Also called ICI D1694. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Ras gene: A gene that has been found to cause cancer when it is altered (mutated). Agents that block its activity may stop the growth of cancer. A ras peptide is a protein fragment produced by the ras gene. [NIH] Ras Proteins: Small, monomeric GTP-binding proteins encoded by ras genes. The protooncogene-derived protein (proto-oncogene protein P21(RAS)) plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (oncogene protein P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation). EC 3.6.1.-. [NIH]
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Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regional chemotherapy: Treatment with anticancer drugs that is directed to a specific area. [NIH]
Regional lymph node: In oncology, a lymph node that drains lymph from the region around a tumor. [NIH] Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]
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Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Reproductive History: An important aggregate factor in epidemiological studies of women's health. The concept usually includes the number and timing of pregnancies and their outcomes, the incidence of breast feeding, and may include age of menarche and menopause, regularity of menstruation, fertility, gynecological or obstetric problems, or contraceptive usage. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Residual disease: Cancer cells that remain after attempts have been made to remove the cancer. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Response rate: treatment. [NIH]
The percentage of patients whose cancer shrinks or disappears after
Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another,
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all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Vein: Central retinal vein and its tributaries. It runs a short course within the optic nerve and then leaves and empties into the superior ophthalmic vein or cavernous sinus. [NIH]
Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [NIH] Ribonucleoproteins: Proteins conjugated with ribonucleic acids (RNA) or specific RNA. Many viruses are ribonucleoproteins. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable
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oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Selenomethionine: Diagnostic aid in pancreas function determination. [NIH] Semen:
The thick, yellowish-white, viscid fluid secretion of male reproductive organs
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discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Semustine: 4-Methyl derivative of lomustine (CCNU). An antineoplastic agent which functions as an alkylating agent. [NIH] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sentinel lymph node mapping: The use of dyes and radioactive substances to identify the first lymph node to which cancer is likely to spread from the primary tumor. Cancer cells may appear first in the sentinel node before spreading to other lymph nodes and other places in the body. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: female or male. [NIH]
The biological characteristics which distinguish human beings as
Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU]
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Sigmoid Colon: The lower part of the colon that empties into the rectum. [NIH] Sigmoidoscope: A thin, lighted tube used to view the inside of the colon. [NIH] Sigmoidoscopy: Endoscopic examination, therapy or surgery of the sigmoid flexure. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Silymarin: A mixture of flavonoids extracted from seeds of the milk thistle, Silybum marianum. It consists primarily of three isomers: silicristin, silidianin, and silybin, its major component. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent. [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoldering leukemia: Disease in which the bone marrow does not function normally. Also called preleukemia or myelodysplastic syndrome. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Security: Government sponsored social insurance programs. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Socioeconomic Factors: Social and economic factors that characterize the individual or group within the social structure. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland,
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27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Dodecyl Sulfate: An anionic surfactant, usually a mixture of sodium alkyl sulfates, mainly the lauryl; lowers surface tension of aqueous solutions; used as fat emulsifier, wetting agent, detergent in cosmetics, pharmaceuticals and toothpastes; also as research tool in protein biochemistry. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic mutations: Alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other diseases. [NIH] Somatomedins: Insulin-like polypeptides made by the liver and some fibroblasts and released into the blood when stimulated by somatotropin. They cause sulfate incorporation into collagen, RNA, and DNA synthesis, which are prerequisites to cell division and growth of the organism. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectroscopic: The recognition of elements through their emission spectra. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphincters: Any annular muscle closing an orifice. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH]
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Splenic Vein: Vein formed by the union (at the hilus of the spleen) of several small veins from the stomach, pancreas, spleen and mesentery. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stoma: A surgically created opening from an area inside the body to the outside. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stool test: A test to check for hidden blood in the bowel movement. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH]
Stromal: Large, veil-like cell in the bone marrow. [NIH] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU]
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Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfates: Inorganic salts of sulfuric acid. [NIH] Sulfides: Chemical groups containing the covalent sulfur bonds -S-. The sulfur atom can be bound to inorganic or organic moieties. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Sulindac: A sulfinylindene derivative whose sulfinyl moiety is converted in vivo to an active anti-inflammatory analgesic that undergoes enterohepatic circulation to maintain constant blood levels without causing gastrointestinal side effects. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Supine: Having the front portion of the body upwards. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU]
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Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Temozolomide: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Tenesmus: Straining, especially ineffectual and painful straining at stool or in urination. [EU]
Terminal Care: Medical and nursing care of patients in the terminal stage of an illness. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders.
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Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thioredoxin: A hydrogen-carrying protein that participates in a variety of biochemical reactions including ribonucleotide reduction. Thioredoxin is oxidized from a dithiol to a disulfide during ribonucleotide reduction. The disulfide form is then reduced by NADPH in a reaction catalyzed by thioredoxin reductase. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombospondin 1: An extracellular matrix glycoprotein from platelets and a variety of normal and transformed cells of both mesenchymal and epithelial origin. Thrombospondin1 is believed to play a role in cell migration and proliferation, during embryogenesis and wound repair. Also, it has been studied for its use as a potential regulator of tumor growth and metastasis. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. [NIH] Thymidine Phosphorylase: The enzyme catalyzing the transfer of 2-deoxy-D-ribose from thymidine to orthophosphate, thereby liberating thymidine. EC 2.4.2.4. [NIH] Thymidylate Synthase: An enzyme of the transferase class that catalyzes the reaction 5,10methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 2.1.1.45. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone,
558 Colon Cancer
which helps regulate growth and metabolism. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Topical: On the surface of the body. [NIH] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle
Dictionary 559
(pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]
Transitional cell carcinoma: A type of cancer that develops in the lining of the bladder, ureter, or renal pelvis. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transverse Colon: The part of the colon that goes across the abdomen from right to left. [NIH]
Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]
Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH] Troglitazone: A drug used in diabetes treatment that is being studied for its effect on reducing the risk of cancer cell growth in fat tissue. [NIH] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [NIH] Trypanosomiasis: Infection with protozoa of the genus Trypanosoma. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH]
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Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]
Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Unresectable: Unable to be surgically removed. [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]
Ureter: One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urokinase: A drug that dissolves blood clots or prevents them from forming. [NIH]
Dictionary 561
Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]
Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Veterinarians: Individuals with a degree in veterinary medicine that provides them with training and qualifications to treat diseases and injuries of animals. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Video Recording: The storing or preserving of video signals for television to be played back later via a transmitter or receiver. Recordings may be made on magnetic tape or discs (videodisc recording). [NIH] Videodisc Recording: The storing of visual and usually sound signals on discs for later reproduction on a television screen or monitor. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb
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nutrients. [NIH] Villous: Of a surface, covered with villi. [NIH] Vimentin: An intermediate filament protein found in most differentiating cells, in cells grown in tissue culture, and in certain fully differentiated cells. Its insolubility suggests that it serves a structural function in the cytoplasm. MW 52,000. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virtual colonoscopy: A method under study to examine the colon by taking a series of xrays (called a CT scan) and then using a high-powered computer to reconstruct 2-D and 3-D pictures of the interior surfaces of the colon from these x-rays. The pictures can be saved, manipulated to better viewing angles, and reviewed after the procedure, even years later. Also called computed tomography colography. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Vitamin D: The vitamin that mediates intestinal calcium absorption, bone calcium metabolism, and probably muscle activity. It usually acts as a hormone precursor, requiring 2 stages of metabolism before reaching actual hormonal form. It is isolated from fish liver oils and used in the treatment and prevention of rickets. [NIH] Vitamin E: Vitamin found largely in plant materials, especially wheat germ, corn, sunflower seed, rapeseed, soybean oils, alfalfa, and lettuce. It is used as an antioxidant in vegetable oils and shortenings. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Wheezing: Breathing with a rasp or whistling sound; a sign of airway constriction or obstruction. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly
Dictionary 563
used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]
Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
565
INDEX 1 1,2-Dimethylhydrazine, 309, 481 A Abdominal Pain, 47, 481, 537, 560 Aberrant, 319, 327, 395, 481, 546 Ablation, 481 Acceptor, 481, 524, 534, 557 Acetaminophen, 312, 481 Acetylcholine, 481, 495, 532 Acrylonitrile, 481, 549 Acute lymphoblastic leukemia, 481 Acute lymphocytic leukemia, 371, 481 Acute myelogenous leukemia, 481 Acute myeloid leukemia, 481 Acute nonlymphocytic leukemia, 481 Adaptability, 481, 493 Adenoma, 11, 29, 31, 43, 55, 377, 384, 413, 482 Adenomatous Polyposis Coli, 46, 380, 396, 400, 482 Adenovirus, 325, 482 Adipocytes, 482, 498, 523 Adjustment, 482 Adjuvant Therapy, 330, 331, 332, 347, 365, 482 Adsorption, 389, 482 Adsorptive, 482 Adverse Effect, 38, 482, 551 Aerobic, 482, 529 Afferent, 482, 523 Affinity, 482, 552 Age Groups, 11, 482 Age of Onset, 51, 482 Age-Adjusted, 17, 43, 51, 440, 482 Aged, 80 and Over, 482 Aggressiveness, 375, 483 Agonists, 388, 389, 483 Airway, 483, 562 Alfalfa, 483, 562 Algorithms, 415, 483, 489 Alimentary, 332, 483, 502, 535, 536 Alkaline, 483, 484, 488, 491 Alkaloid, 483, 488, 491, 496 Alkylating Agents, 483, 556, 560 Alkylation, 483 Alleles, 380, 396, 400, 483 Allergen, 483, 551 Allogeneic, 483, 513, 537
Allylamine, 483 Alpha Particles, 483, 545 Alternative medicine, 424, 483 Amine, 483, 516 Amino Acid Sequence, 370, 374, 394, 484, 485, 512 Ammonia, 483, 484 Amniotic Fluid, 484, 526 Amplification, 484 Ampulla, 484, 505 Anaerobic, 484, 506 Anaesthesia, 484, 519 Anal, 46, 346, 408, 449, 452, 484, 506, 508, 509, 530 Anal Fissure, 46, 484 Analgesic, 481, 484, 498, 531, 555 Analog, 332, 484, 509, 510 Analogous, 484, 559 Anaphase, 484 Anaphylatoxins, 484, 497 Anatomical, 30, 309, 484, 494, 519, 539, 550 Anchorage, 484 Anemia, 5, 36, 47, 334, 443, 477, 484, 509 Anesthesia, 483, 484, 498 Aneuploidy, 484 Angina, 485 Anginal, 485, 532 Angiogenesis inhibitor, 307, 313, 485 Angioma, 485 Animal model, 9, 485 Anionic, 485, 553 Anions, 328, 485, 522 Annealing, 485, 540 Anode, 485 Anoikis, 485 Anorexia, 47, 485, 560 Antagonism, 485 Antiangiogenic, 485 Antibacterial, 44, 485, 553 Antibiotic, 46, 334, 485, 500, 503, 529, 536, 553, 556 Antibody therapy, 349, 351, 355, 359, 485 Anticarcinogenic, 485 Anticoagulant, 485, 543 Anticonvulsants, 385, 486 Antidote, 486, 523 Antigen-Antibody Complex, 486, 497 Anti-infective, 486, 517
566 Colon Cancer
Anti-Inflammatory Agents, 5, 486, 487, 493 Antimetabolite, 486, 501, 509, 528 Antimetastatic, 486 Antineoplastic, 483, 486, 491, 503, 509, 510, 512, 520, 528, 529, 535, 551, 555 Antineoplastons, 327, 342, 486 Antioxidant, 11, 20, 486, 534, 552, 562 Antiproliferative, 322, 486, 521 Antipyretic, 481, 486 Antitumour, 486 Antiviral, 486, 510, 520, 521 Anus, 53, 484, 486, 488, 490, 496, 505, 547 Anxiety, 38, 422, 486, 498 Appendicitis, 407, 486 Applicability, 50, 486 Approximate, 12, 486 Aqueous, 487, 488, 500, 517, 553 Arachidonic Acid, 387, 487, 503, 523, 543 Arginine, 484, 487, 532, 534, 545, 559 Arrhythmia, 487, 561 Arterial, 483, 487, 509, 517, 543 Arteries, 416, 487, 490, 499, 525, 528, 531, 557 Arterioles, 487, 490, 491, 531 Asbestos, 487, 497 Ascending Colon, 389, 403, 487 Aspirin, 5, 15, 20, 22, 311, 329, 417, 420, 453, 487 Assay, 23, 42, 375, 394, 487, 518 Ataxia, 443, 487, 556 ATP, 487, 495, 502, 512, 538, 543, 557, 558 Atrophy, 443, 487 Autacoids, 487, 519 Autodigestion, 487, 535 Autologous, 487, 537 Autonomic, 481, 487 Azoxymethane, 319, 320, 325, 487 B Back Pain, 425, 487 Bacteremia, 487 Bacterial toxin, 488 Bacteriophage, 488, 558 Barbiturate, 488, 556 Basal Ganglia, 386, 487, 488, 533 Basal Ganglia Diseases, 487, 488 Base, 178, 488, 500, 501, 510, 512, 522, 540, 560 Base Sequence, 488, 510, 512 Basement Membrane, 488, 507, 522 Basophils, 488, 514, 523
Benign, 13, 22, 52, 403, 456, 465, 482, 488, 491, 531, 546 Berberine, 488 Beta-Glucosidase, 313, 488 Bevacizumab, 342, 351, 449, 452, 489 Bilateral, 416, 489 Bile, 334, 339, 346, 384, 489, 494, 501, 505, 510, 511, 517, 522, 524, 526, 542, 556, 561 Bile Acids, 384, 489, 511, 556 Bile Acids and Salts, 489 Bile duct, 346, 489, 510, 542 Bile Pigments, 489, 522, 526 Biliary, 346, 369, 489, 535 Biliary Tract, 346, 489, 535 Bilirubin, 489, 510, 517 Biochemical reactions, 489, 557 Biological response modifier, 489, 520 Biological therapy, 489, 514 Biopsy, 18, 22, 46, 371, 390, 478, 489, 537 Biotechnology, 175, 380, 409, 424, 437, 442, 443, 444, 489 Biotransformation, 489 Bladder, 371, 407, 448, 467, 490, 497, 543, 548, 559, 560 Blastomyces, 490, 535 Bloating, 46, 467, 490 Blood Coagulation, 490, 491, 508, 557 Blood Glucose, 490, 515, 520 Blood Platelets, 490, 551 Blood pressure, 425, 490, 492, 517, 529, 532, 540, 553 Body Fluids, 489, 490, 491, 503, 552, 560 Body Mass Index, 19, 20, 490, 534 Bolus, 490 Bolus infusion, 490 Bone Marrow, 481, 490, 511, 514, 518, 525, 531, 537, 541, 552, 553, 554 Bone Marrow Cells, 490, 514 Bone scan, 490, 550 Boron, 490, 500 Bowel Movement, 306, 376, 395, 458, 490, 502, 554 Bowel Prep, 7, 26, 28, 30, 38, 490 Brachytherapy, 490, 521, 522, 545, 563 Bradykinin, 491, 532 Branch, 308, 312, 475, 491, 504, 512, 525, 536, 544, 553, 557 Breakdown, 491, 502, 510 Bronchi, 491, 506, 558 Bronchial, 491, 516 Bypass, 491
Index 567
C Calcium channel blocker, 491, 561 Caloric intake, 413, 491 Camptothecin, 330, 331, 491, 522 Cancer vaccine, 341, 491 Capillary, 379, 491, 561 Carbohydrate, 491, 513, 540 Carbon Dioxide, 26, 491, 501, 509, 539, 548 Carboplatin, 343, 491 Carcinogen, 9, 481, 487, 491, 530 Carcinogenic, 9, 14, 20, 483, 491, 520, 534, 542 Carcinoid, 448, 463, 491 Cardiac, 179, 415, 483, 492, 499, 504, 506, 510, 531 Cardiovascular, 17, 492, 523, 551 Cardiovascular disease, 17, 492 Carotene, 20, 492, 548 Carotenoids, 492 Case report, 325, 492 Case series, 44, 492 Case-Control Studies, 11, 24, 37, 40, 45, 49, 52, 405, 412, 492, 506 Caspase, 323, 492 Caspase 1, 492 Cathode, 485, 492 Cations, 492, 522 Caudal, 492, 533, 541 Caudate Nucleus, 488, 492, 533 Causal, 11, 21, 492, 506, 521 Cause of Death, 4, 23, 53, 368, 377, 378, 386, 391, 492 CDC2, 492 Cecum, 26, 55, 389, 492, 523 Celecoxib, 312, 493 Cell Adhesion, 308, 493, 520 Cell Adhesion Molecules, 493 Cell Death, 486, 493, 507 Cell Differentiation, 493, 552 Cell Division, 443, 484, 488, 493, 514, 529, 539, 553 Cell membrane, 311, 493, 501, 538 Cell Membrane Permeability, 311, 493 Cell motility, 493, 516 Cell proliferation, 324, 366, 375, 493, 552 Cell Respiration, 493, 529, 548 Cell Survival, 493, 514 Cell Transplantation, 346, 493 Cellobiose, 493 Cellulose, 319, 493, 539 Central Nervous System, 386, 481, 493, 494, 510, 513, 523, 551
Central retinal vein, 493, 549 Ceramide, 312, 493 Cerebellar, 487, 493, 547 Cerebral, 487, 488, 493, 494, 506, 556 Cerebral Cortex, 487, 493 Cerebrovascular, 488, 492, 494, 556 Cerebrum, 493, 494, 556, 560 Cervical, 52, 406, 494 Cervix, 494, 497, 514, 522 Checkup, 32, 494 Chemoembolization, 357, 358, 494 Chemokines, 494 Chemopreventive, 8, 44, 47, 327, 494 Chemoprotective, 366, 494 Chemotactic Factors, 494, 497 Chemotherapeutic agent, 323, 375, 386, 494 Chenodeoxycholic Acid, 494, 561 Chest Pain, 415, 494 Chin, 494, 527 Cholecystokinin, 385, 494 Choleretic, 494, 495, 501, 524, 561 Cholesterol, 407, 409, 489, 495, 499, 510, 525, 527, 546, 550 Choline, 495 Choline Kinase, 495 Cholinergic, 495 Chondrocytes, 495, 508 Chromatin, 486, 495, 532 Chromosomal, 369, 484, 495, 539, 549 Chronic Disease, 40, 406, 439, 452, 457, 458, 495 Chronic renal, 495, 540, 560 Cirrhosis, 416, 495, 515, 540, 542 CIS, 449, 452, 495, 548 Cisplatin, 312, 316, 327, 330, 495 Clear cell carcinoma, 495, 501 Clinical Medicine, 495, 541 Cloning, 370, 489, 495 Coagulation, 490, 495, 515, 557 Codon, 178, 496, 512 Coenzyme, 496, 525 Cofactor, 496, 543, 557 Cohort Studies, 496, 506 Colchicine, 496, 560 Colectomy, 5, 42, 355, 380, 454, 496 Colitis, 5, 18, 23, 35, 36, 42, 45, 46, 334, 407, 411, 413, 416, 455, 456, 458, 496, 497, 519, 542, 560 Collagen, 484, 488, 496, 507, 508, 511, 526, 539, 553 Colloidal, 496, 504
568 Colon Cancer
Colon Polyps, 4, 12, 35, 426, 454, 456, 496 Colonic Polyps, 7, 20, 45, 52, 379, 380, 448, 496 Colonoscope, 34, 496 Colorectal Neoplasms, 21, 341, 496 Colostomy, 356, 406, 416, 450, 497 Combination chemotherapy, 325, 345, 347, 348, 349, 351, 353, 356, 497 Combination Therapy, 497 Complement, 33, 374, 378, 387, 394, 484, 497, 512, 520, 522, 551 Complementary and alternative medicine, 319, 338, 497 Complementary medicine, 319, 497 Complete remission, 497, 548 Complete response, 497 Compliance, 7, 17, 22, 25, 35, 41, 44, 45, 46, 52, 55, 376, 395, 440, 497 Computational Biology, 437, 442, 497 Computed tomographic colonography, 344, 498 Computed tomography, 5, 7, 28, 30, 35, 40, 455, 498, 550, 562 Computerized tomography, 498 Conception, 498, 508, 553 Concomitant, 498 Confounding, 498 Conjugated, 367, 372, 381, 382, 397, 489, 494, 498, 500, 501, 524, 549 Conjugation, 489, 498 Connective Tissue, 490, 496, 498, 508, 510, 511, 525, 527, 549, 556 Connective Tissue Cells, 498 Conscious Sedation, 6, 498 Consciousness, 484, 498, 544 Constipation, 47, 333, 415, 456, 478, 498, 537 Constitutional, 48, 498 Constriction, 499, 522, 562 Contamination, 499 Contraindications, ii, 499 Control group, 10, 37, 499 Controlled study, 499 Coronary, 43, 492, 499, 528, 531 Coronary Disease, 499 Coronary heart disease, 43, 492, 499 Coronary Thrombosis, 499, 528, 531 Coronary Vessels, 499 Cortex, 499, 507, 547 Cortisone, 499, 502 Cost-benefit, 7, 40, 499 Cost-Benefit Analysis, 7, 499
Criterion, 26, 499 Cross-Sectional Studies, 499, 506 Cryosurgery, 313, 331, 499 Cues, 44, 499 Curative, 18, 35, 177, 376, 394, 500, 532, 549, 557 Curcumin, 308, 344, 500 Cyclic, 500, 514, 532, 538, 543 Cyclin, 326, 500 Cytochrome, 323, 500 Cytokine, 500, 520, 536, 557 Cytomegalovirus, 500, 510 Cytomegalovirus Infections, 500, 510 Cytoplasm, 486, 488, 493, 500, 506, 532, 549, 562 Cytosine, 500, 545 Cytoskeleton, 500, 520, 528 Cytotoxic, 313, 331, 349, 378, 384, 500, 545, 546, 552 Cytotoxicity, 312, 330, 378, 483, 495, 500, 522 D Dairy Products, 411, 500, 549 Data Collection, 500, 509 Daunorubicin, 500, 503 Decarboxylation, 501, 516, 545 Decision Making, 15, 25, 501 Defense Mechanisms, 501, 520 Degenerative, 501, 515 Deletion, 486, 501 Denaturation, 501, 540 Density, 23, 490, 501, 534, 540 Dental Care, 25, 501 Dentists, 12, 51, 501 Deoxycholic Acid, 384, 501 Deoxyguanosine, 325, 501 Deoxyuridine, 501, 557 Depolarization, 501, 552 DES, 351, 402, 484, 501 Descending Colon, 55, 389, 403, 501 Desmoid tumor, 369, 501 Deuterium, 501, 517 Developed Countries, 401, 501 Dexamethasone, 344, 501 Diabetes Mellitus, 502, 513, 515 Diagnostic procedure, 4, 344, 363, 424, 502 Dialysate, 502, 503 Diarrhea, 47, 346, 415, 421, 456, 463, 478, 502, 505, 506 Dietary Fiber, 11, 20, 39, 43, 50, 402, 460, 502 Diethylcarbamazine, 502, 555
Index 569
Difluoromethylornithine, 16, 502 Digestion, 11, 387, 409, 483, 489, 490, 502, 521, 524, 536, 554 Digestive system, 360, 502, 511, 530 Digestive tract, 374, 502, 552 Digital rectal examination, 8, 24, 36, 44, 50, 51, 53, 377, 385, 411, 439, 456, 458, 502 Dihydrotestosterone, 502, 547 Dihydroxy, 378, 502 Dilatation, 502, 542 Dimethyl, 312, 502 Diploid, 484, 502, 530, 539, 559 Direct, iii, 26, 28, 34, 38, 44, 49, 53, 412, 429, 495, 502, 525, 547 Dissection, 502, 525 Distal, 12, 13, 29, 31, 33, 38, 39, 41, 43, 46, 47, 51, 53, 308, 407, 412, 502, 511, 544 Distention, 27, 502 Diverticula, 46, 502 Diverticulitis, 502 Diverticulosis, 53, 502, 533 Diverticulum, 502 DNA Topoisomerase, 502, 512 Double-blind, 16, 503 Double-blinded, 503 Doxorubicin, 503 Drug Interactions, 311, 328, 430, 503 Drug Resistance, 503 Drug Tolerance, 503, 558 Duct, 484, 503, 507, 534, 549 Duodenum, 352, 387, 489, 503, 505, 535, 554 Dwell time, 33, 503 Dyes, 488, 503, 525, 532, 551 Dysplasia, 5, 18, 29, 55, 403, 443, 503 Dystrophy, 443, 503 E Eating Disorders, 407, 503 Ectopic, 395, 503 Edrecolomab, 324, 355, 503 Effector, 378, 481, 497, 503, 522, 538 Effector cell, 378, 503, 522 Efficacy, 13, 26, 42, 51, 307, 322, 325, 406, 439, 503, 542, 559 Eicosanoids, 387, 503 Elastin, 496, 504, 507 Elective, 5, 504 Electrocoagulation, 496, 504 Electrolysis, 485, 492, 504 Electrolyte, 504, 541, 553, 560 Electrophoresis, 504
Electrophysiological, 504, 561 Ellagic Acid, 504 Embryo, 493, 504, 519 Embryogenesis, 504, 557 Emollient, 504, 513, 533 Endemic, 504, 554 Endocarditis, 46, 504 Endocardium, 504 Endocrine Glands, 386, 504 Endogenous, 11, 503, 504, 514, 558 Endometrial, 34, 51, 504 Endometriosis, 175, 504 Endometrium, 504, 514 Endoscope, 43, 450, 505 Endoscopic, 8, 16, 43, 48, 352, 385, 411, 415, 496, 505, 542, 552 Endothelial cell, 504, 505, 508, 557 Endothelium, 505, 532, 539 Endothelium, Lymphatic, 505 Endothelium, Vascular, 505 Endothelium-derived, 505, 532 Endotoxin, 505, 560 End-stage renal, 495, 505, 540 Enema, 5, 8, 10, 13, 21, 22, 24, 25, 26, 31, 32, 34, 35, 36, 37, 40, 41, 42, 45, 46, 48, 49, 50, 51, 53, 54, 344, 383, 398, 399, 411, 439, 449, 454, 455, 456, 458, 488, 505 Energy balance, 505, 523 Energy Intake, 20, 43, 505 Enhancer, 395, 505 Enterohepatic, 505, 555 Enterohepatic Circulation, 505, 555 Enteropeptidase, 505, 559 Enterotoxins, 505 Environmental Exposure, 505, 533 Environmental Health, 436, 438, 505 Enzymatic, 484, 491, 492, 497, 505, 516, 527, 540, 548 Eosinophil, 506, 514 Epidemic, 506, 554 Epidemiologic Studies, 340, 506 Epidemiological, 8, 11, 17, 20, 36, 50, 52, 426, 506, 548 Epidermal, 176, 364, 380, 506, 527 Epidermal Growth Factor, 364, 380, 506 Epidermal growth factor receptor, 176, 364, 380, 506 Epidermis, 506 Epinephrine, 506, 532, 560 Epithelial, 24, 55, 364, 365, 366, 384, 387, 482, 506, 513, 516, 522, 530, 557
570 Colon Cancer
Epithelial Cells, 55, 365, 366, 384, 387, 506, 516, 522, 530 Epithelium, 41, 380, 387, 396, 400, 488, 505, 506, 510 Epitope, 23, 308, 371, 506 Erythrocytes, 484, 490, 506, 547, 551 Escalation, 506 Escherichia, 506 Escherichia coli, 506 Esophageal, 346, 348, 507 Esophagitis, 416, 507 Esophagus, 410, 416, 417, 502, 507, 511, 525, 537, 554 Essential Tremor, 443, 507 Estradiol, 329, 507 Estrogen, 309, 326, 507, 546, 550 Estrogen receptor, 326, 507 Eukaryotic Cells, 492, 507, 519, 533 Evacuation, 498, 507, 523, 545 Exhaustion, 485, 507 Exisulind, 352, 507 Exocrine, 494, 507, 535 Exogenous, 387, 482, 489, 504, 507, 514 Expert Testimony, 467, 507 External-beam radiation, 507, 522, 545, 563 Extracellular Matrix, 312, 331, 485, 498, 507, 508, 520, 526, 557 Extracellular Matrix Proteins, 507, 526 Extracellular Space, 507 Eye Infections, 482, 507 F Faecal, 175, 508 Fallopian tube, 508, 514 False Positive Reactions, 21, 508 Familial polyposis, 43, 497, 508 Family Planning, 437, 508 Farnesyl, 508 Fathers, 19, 508 Fatigue, 36, 47, 340, 407, 467, 508, 515 Fatty acids, 11, 311, 503, 508, 513, 526, 543 Fecal Incontinence, 416, 508 Feces, 379, 491, 498, 508, 554 Ferritin, 508 Fetus, 508, 526, 539, 561 Fibrin, 490, 508, 537, 539, 557 Fibrinogen, 508, 539, 557 Fibroblast Growth Factor, 508 Fibroblasts, 498, 508, 520, 521, 553 Fibronectins, 507, 508 Fibrosis, 443, 483, 508, 550 Fixation, 509, 551
Flatus, 416, 508, 509, 510 Flavopiridol, 308, 322, 509 Floxuridine, 313, 331, 344, 509 Fluorescence, 509 Fluorouracil, 309, 310, 311, 313, 323, 324, 325, 326, 327, 328, 330, 331, 332, 336, 342, 343, 344, 345, 347, 349, 350, 353, 356, 357, 367, 372, 374, 375, 382, 420, 431, 461, 509, 523 Flushing, 463, 509 Focus Groups, 310, 326, 509 Fold, 21, 50, 509, 527 Folic Acid, 12, 16, 39, 306, 315, 509, 523 Follicular large cell lymphoma, 349, 509 Forearm, 490, 509 Frameshift, 177, 510 Frameshift Mutation, 510 Free Radicals, 486, 510 Fructans, 370, 510 Fructose, 510, 521 Fungi, 402, 490, 498, 507, 510, 514, 521, 528, 563 G Gallbladder, 346, 407, 481, 489, 494, 502, 510, 511 Gallstones, 411, 489, 494, 510, 561 Gamma Rays, 510, 530, 545, 546 Gamma-interferon, 510 Ganciclovir, 510 Ganglia, 481, 488, 510, 531 Ganglioside, 179, 510 Gas, 13, 416, 484, 491, 509, 510, 517, 520, 530, 532, 555, 561 Gastric Juices, 510, 536 Gastric Mucosa, 510, 536 Gastrin, 510, 511, 517 Gastrin-Releasing Peptide, 511 Gastroenterologist, 511 Gastroesophageal Reflux, 411, 415, 511 Gastrointestinal tract, 46, 350, 356, 366, 379, 386, 488, 491, 509, 511, 523, 551, 554, 560 Gelatin, 511, 513, 557 Gemcitabine, 511 Gene Amplification, 511 Gene Expression, 176, 179, 444, 511 Gene Rearrangement, 511 Gene Silencing, 177, 511 Gene Therapy, 340, 354, 482, 511 Gene-modified, 512 General practitioner, 31, 512 Genetic Code, 512, 533
Index 571
Genetic Counseling, 6, 46, 464, 466, 468, 512 Genetic Engineering, 489, 495, 512 Genetic Markers, 364, 512 Genistein, 326, 331, 512 Genotype, 14, 50, 512, 538 Germ-free, 512 Germline mutation, 401, 512, 516 Ginseng, 309, 323, 512 Gland, 499, 512, 525, 530, 535, 539, 543, 546, 550, 554, 555, 557 Glomerular, 512, 521 Glucocorticoid, 501, 512 Glucose, 320, 443, 488, 490, 493, 502, 512, 513, 515, 520 Glucose Intolerance, 502, 512 Glucuronic Acid, 513, 515 Glutamate, 340, 513 Glutamic Acid, 509, 513, 532 Glutathione Peroxidase, 513, 550 Glycerol, 513, 538 Glycerophospholipids, 513, 538 Glycine, 484, 489, 494, 501, 513, 524, 532, 551 Glycogen, 513 Glycogen Synthase, 513 Glycoprotein, 23, 369, 376, 394, 491, 508, 513, 514, 522, 557, 560 Glycosaminoglycans, 507, 513 Glycosidic, 493, 513, 531, 533 Goats, 500, 513 Goblet Cells, 23, 513 Governing Board, 513, 541 Grade, 5, 18, 29, 349, 513 Graft, 513, 517, 518 Graft Rejection, 513, 518 Grafting, 513, 519 Gram-negative, 506, 514 Granulocyte, 514 Granulocyte-Macrophage ColonyStimulating Factor, 514 Granuloma, 514, 535 Grasses, 509, 514 Group Practice, 31, 415, 514 Growth factors, 514, 520 Growth Inhibitors, 403, 514 Guanine, 501, 514, 545 Guanylate Cyclase, 514, 532 Gynecologic cancer, 34, 514 H Habitual, 44, 514 Hawaii, 179, 473, 514
Health Education, 30, 515 Health Policy, 406, 515 Health Services, 32, 438, 515 Health Status, 41, 515 Heart attack, 492, 515 Heart failure, 463, 515 Hematogenous, 17, 515 Heme, 376, 379, 394, 412, 489, 500, 515, 535 Hemochromatosis, 515 Hemoglobin, 379, 412, 484, 506, 515 Hemoglobin A, 412, 515 Hemoglobinopathies, 511, 515 Hemoglobinuria, 443, 515 Hemorrhage, 504, 515, 554 Hemorrhoids, 46, 306, 515 Hemostasis, 515, 520, 551 Heparin, 515 Hepatic, 313, 331, 373, 383, 396, 509, 515 Hepatitis, 415, 515 Hepatocyte, 516 Hepatocyte Growth Factor, 516 Hepatoma, 516 Hereditary mutation, 512, 516 Heredity, 401, 439, 511, 512, 516 Hernia, 516 Herpes, 516 Herpes Zoster, 516 Heterodimers, 516, 520, 559 Heterogeneity, 15, 482, 516 Heterotrophic, 510, 516 Histamine, 337, 484, 516 Histidine, 516, 520 Histology, 7, 45, 311, 516, 535 Homeobox, 516 Homeostasis, 516 Homeotic, 516 Homodimer, 516, 559 Homologous, 483, 511, 516, 520, 544, 551, 555 Homotypic, 516 Hormonal, 487, 516, 537, 562 Hormone Replacement Therapy, 439, 517 Hormone therapy, 482, 517 Host, 365, 388, 488, 517, 518, 523, 540, 549, 561, 562 Humoral, 378, 513, 517 Humour, 517 Hybrid, 42, 517 Hybridization, 375, 517 Hybridoma, 371, 517
572 Colon Cancer
Hydrogen, 313, 481, 483, 488, 491, 501, 507, 513, 517, 524, 529, 532, 533, 534, 544, 557 Hydrogen Peroxide, 313, 513, 517, 524 Hydrolysis, 488, 489, 493, 495, 517, 531, 538, 544, 559 Hydroxyproline, 484, 496, 517 Hyperbilirubinemia, 517, 522 Hyperplasia, 517 Hypersensitivity, 483, 506, 517, 523, 551 Hypertension, 492, 517, 540, 560 Hyperthermia, 410, 517 Hypertrophy, 517 Hypnotic, 488, 518, 556 Hypoxia, 518, 556 I Id, 314, 332, 448, 449, 459, 460, 461, 462, 474, 476, 518 Idiotype, 518 Ileal, 518 Ileostomy, 356, 416, 450, 518 Ileum, 492, 518 Ileus, 356, 518 Immune function, 518, 559 Immune system, 341, 347, 407, 485, 489, 503, 518, 523, 525, 526, 561, 562 Immunity, 378, 518, 533 Immunization, 518, 542, 551 Immunoassay, 379, 518 Immunodeficiency, 443, 518 Immunogenic, 390, 392, 518 Immunoglobulin, 485, 518, 529 Immunohistochemistry, 518 Immunologic, 494, 518, 536, 546 Immunology, 482, 518, 534 Immunosuppressant, 483, 509, 518, 528 Immunosuppressive, 512, 518 Immunosuppressive therapy, 518 Immunotherapy, 347, 358, 367, 392, 489, 518 Immunotoxin, 348, 518 Impairment, 487, 507, 519, 527 Implant radiation, 519, 521, 522, 545, 563 Implantation, 498, 519 In situ, 440, 519 In Situ Hybridization, 519 Incision, 496, 519, 521, 523 Incompetence, 511, 519 Indicative, 369, 375, 383, 398, 408, 519, 536, 561 Indolent, 509, 519 Indomethacin, 519
Induction, 313, 320, 322, 323, 325, 332, 519, 545 Infant, Newborn, 482, 519 Infarction, 499, 519, 528, 531 Infiltrating cancer, 519, 522 Infiltration, 519 Infusion, 332, 509, 520 Initiation, 312, 378, 520, 558 Inorganic, 495, 520, 530, 539, 555 Insecticides, 520, 563 Insight, 45, 520 Insufflation, 26, 30, 46, 520 Insulin, 21, 520, 553 Insulin-dependent diabetes mellitus, 520 Insulin-like, 520, 553 Insulin-Like Growth Factor Binding Protein 3, 520 Integrins, 520 Interferon, 378, 431, 510, 520, 525 Interferon Alfa-2a, 520 Interferon-alpha, 520 Interferon-beta, 520 Interleukin-1, 340, 492, 521 Interleukin-10, 521 Interleukin-2, 521 Interleukin-6, 521 Intermittent, 521, 537 Internal Medicine, 10, 14, 24, 51, 310, 311, 321, 389, 511, 521 Internal radiation, 521, 522, 545, 563 Interstitial, 490, 507, 521, 522, 563 Intervention Studies, 11, 413, 521 Intestinal Flora, 311, 521 Intestinal Mucosa, 494, 521 Intestinal Polyps, 439, 521 Intestine, 373, 389, 465, 489, 490, 496, 505, 506, 521, 523 Intoxication, 521, 563 Intracellular, 519, 520, 521, 527, 532, 541, 543, 547, 550, 552 Intraepithelial, 521 Intrahepatic, 344, 346, 521 Intraperitoneal, 521 Intravenous, 329, 520, 521, 535 Intrinsic, 482, 488, 521 Inulin, 370, 521 Invasive, 22, 29, 344, 352, 354, 376, 380, 383, 390, 394, 396, 398, 399, 400, 406, 438, 518, 519, 521, 522, 526 Invasive cancer, 29, 380, 396, 400, 519, 522 Invasive cervical cancer, 406, 522 Involuntary, 488, 507, 508, 522, 531, 552
Index 573
Ionizing, 483, 505, 522, 546 Ions, 488, 504, 517, 522, 544 Irradiation, 497, 522, 563 Irrigation, 416, 522 Ischemia, 487, 510, 522 Isothiocyanates, 522 Isozymes, 522 J Jaundice, 36, 517, 522 Joint, 412, 522, 555, 556 K Karyotype, 178, 522 Kb, 436, 522 Kidney Disease, 360, 436, 443, 522 Killer Cells, 522 Kinetics, 522 L Labile, 497, 522 Laminin, 488, 507, 522 Laparoscopic-assisted colectomy, 355, 496, 523 Laparotomy, 320, 523 Large Intestine, 352, 366, 371, 372, 373, 374, 382, 389, 456, 492, 496, 502, 521, 523, 547, 552 Latent, 523, 540, 541 Laxative, 494, 523 Least-Squares Analysis, 523, 547 Lectin, 523, 527, 529 Leptin, 523 Leukemia, 332, 344, 346, 353, 354, 355, 357, 442, 443, 503, 511, 523, 541 Leukocytes, 488, 490, 494, 519, 520, 523, 532, 560 Leukotrienes, 324, 487, 503, 523 Levamisole, 367, 372, 375, 382, 523 Library Services, 474, 523 Life cycle, 407, 510, 523 Life Expectancy, 41, 523 Ligament, 508, 523, 543 Ligands, 493, 520, 523 Ligation, 524 Likelihood Functions, 524, 547 Linear Models, 524, 547 Linkage, 19, 20, 368, 463, 493, 512, 524 Lipid, 495, 513, 520, 524, 534 Lipid Peroxidation, 524, 534 Lipopolysaccharide, 514, 524 Liposomes, 524 Lithocholic Acid, 524 Liver metastases, 325, 327, 344, 354, 357, 358, 524
Liver scan, 524, 550 Localization, 372, 382, 518, 524 Localized, 17, 37, 41, 43, 368, 390, 391, 392, 509, 519, 522, 524, 539, 560 Locoregional, 381, 400, 524 Logistic Models, 524, 547 Lomustine, 524, 551 Loop, 395, 416, 516, 518, 524, 535 Lovastatin, 524 Low-density lipoprotein, 525 Lower Esophageal Sphincter, 511, 525 Lucida, 522, 525 Lumbar, 487, 525 Lumen, 505, 521, 525 Lupus, 525, 556 Lymph node mapping, 525 Lymphadenectomy, 410, 525 Lymphatic, 381, 397, 485, 505, 509, 519, 525, 527, 553, 557 Lymphatic system, 509, 525, 553, 557 Lymphoblasts, 481, 525 Lymphocyte, 349, 486, 522, 525, 526 Lymphocytic, 525 Lymphoid, 383, 395, 398, 485, 525 Lymphokine, 525 Lymphokine-activated killer cells, 525 Lymphoma, 332, 349, 371, 443, 509, 525 Lysine, 520, 526, 559 Lytic, 526, 551 M Macrophage, 514, 521, 526 Magnetic Resonance Imaging, 27, 526, 550 Malabsorption, 443, 526 Malignant tumor, 384, 497, 526, 530 Malnutrition, 487, 526, 530 Mammography, 40, 405, 526 Mass Screening, 379, 526 Matrilysin, 526 Matrix metalloproteinase, 526 Meat, 12, 14, 15, 20, 22, 44, 50, 306, 307, 313, 377, 379, 526, 549 Meat Products, 50, 526 Meconium, 370, 526 Mediate, 380, 493, 522, 526 Mediator, 494, 521, 526, 551 Medical Records, 4, 54, 526 Medical Staff, 503, 526 Medically Uninsured, 29, 526 Medicament, 370, 527 MEDLINE, 11, 24, 45, 437, 442, 444, 527 Megacolon, 407, 527 Megaloblastic, 501, 509, 527
574 Colon Cancer
Melanin, 527, 538, 560 Melanocytes, 527 Melanoma, 346, 347, 406, 410, 443, 527 Melanosis, 527 Membrane Lipids, 527, 538 Membrane Proteins, 524, 527 Memory, 485, 527 Menarche, 527, 548 Meningeal, 527 Meninges, 493, 527 Menopause, 334, 407, 439, 527, 541, 548 Menstruation, 527, 548 Mental, v, 361, 436, 441, 444, 494, 508, 519, 527, 542, 544, 550, 551, 560 Mental Disorders, 361, 527, 542 Mental Health, v, 361, 436, 441, 527, 542, 544 Mesenchymal, 506, 514, 527, 557 Mesenteric, 374, 527, 540 Mesentery, 527, 528, 537, 554 Meta-Analysis, 177, 528 Metabolite, 386, 489, 502, 523, 524, 528, 542 Metaplasia, 528 Metastasize, 374, 381, 394, 397, 465, 501, 528, 550 Metastatic cancer, 47, 358, 528 Methionine, 307, 502, 528, 555 Methotrexate, 337, 528 MI, 14, 20, 176, 312, 479, 528 Microbe, 528, 558 Micronutrients, 20, 528 Microorganism, 496, 528, 562 Micro-organism, 514, 528, 538 Microscopy, 488, 528, 533 Microspheres, 528 Microtubules, 528, 535 Migration, 528, 557 Milk Thistle, 529, 552 Milligram, 16, 529 Milliliter, 23, 529 Millimeter, 30, 529 Mistletoe lectin, 313, 331, 529 Mitochondria, 529 Mitomycin, 529 Mitosis, 486, 492, 529 Mitotic, 529, 562 Modeling, 529 Modification, 44, 327, 484, 512, 529, 545 Modulator, 529 Monitor, 393, 491, 529, 532, 561
Monoclonal antibodies, 311, 349, 351, 355, 359, 371, 381, 397, 503, 529 Monocyte, 529 Mononuclear, 378, 514, 529, 560 Monophosphate, 509, 530 Monosomy, 484, 530 Morphogenesis, 17, 530 Motility, 380, 519, 530, 551 Motion Sickness, 530, 531 Mucilaginous, 526, 530 Mucinous, 347, 467, 530 Mucinous Adenocarcinoma, 347, 530 Mucins, 371, 513, 530 Mucosa, 7, 16, 28, 178, 179, 384, 510, 525, 530 Mucositis, 530, 557 Mucus, 47, 384, 385, 387, 467, 530, 544, 560 Multicenter study, 26, 530 Multidrug resistance, 530 Multivariate Analysis, 43, 530 Muscle Fibers, 530, 559 Muscular Atrophy, 443, 530 Muscular Dystrophies, 503, 530 Mustard Gas, 530 Mutagen, 14, 402, 530 Mutagenic, 14, 483, 530 Mutagenicity, 530 Mutate, 530 Mycosis, 531, 535 Myelodysplastic syndrome, 531, 552 Myelogenous, 531 Myeloma, 332, 517, 531 Myelosuppression, 374, 531 Myocardial Ischemia, 499, 531 Myocardium, 528, 531 Myotonic Dystrophy, 443, 531 N N-acetyl, 14, 23, 513, 531 Nausea, 47, 531, 560 Neoplasia, 9, 17, 23, 24, 26, 29, 31, 53, 55, 369, 379, 384, 443, 531 Neoplasm, 5, 367, 372, 377, 382, 531, 549, 560 Neoplastic, 9, 52, 55, 177, 364, 365, 366, 381, 397, 525, 531, 546 Nephropathy, 522, 531 Nerve, 484, 487, 494, 526, 531, 532, 541, 548, 549, 550, 554, 559 Nervous System, 443, 482, 493, 526, 531, 532, 555 Networks, 467, 531 Neural, 482, 517, 531, 537
Index 575
Neuraminidase, 23, 371, 531 Neuromuscular, 481, 532, 560 Neuromuscular Junction, 481, 532 Neuropeptide, 511, 532 Neurotoxic, 487, 532 Neurotransmitter, 481, 484, 491, 513, 516, 532, 552, 555 Neutrons, 483, 522, 532, 545 Neutrophils, 514, 516, 523, 532 Niacin, 532, 559 Nifedipine, 532 Nitric Oxide, 327, 532 Nitrogen, 483, 507, 509, 532, 559 Node-negative, 532 Node-positive, 532 Nonmalignant, 13, 532 Nuclear, 176, 178, 307, 310, 326, 488, 491, 498, 507, 510, 532, 533, 545 Nuclear Matrix, 178, 532 Nuclear Pore, 533 Nuclei, 381, 397, 483, 498, 511, 512, 526, 529, 532, 533, 540, 544 Nucleic Acid Hybridization, 517, 533 Nucleolus, 533, 549 Nucleus, 386, 395, 486, 488, 495, 500, 501, 507, 510, 529, 532, 533, 544, 554, 556 Nucleus Accumbens, 386, 533 Nurse Practitioners, 4, 533 Nursing Care, 533, 556 O Occult Bleeding, 47, 533 Occult Blood, 4, 5, 7, 8, 9, 10, 12, 13, 14, 15, 18, 21, 22, 24, 25, 26, 27, 28, 29, 31, 32, 33, 34, 35, 36, 37, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 175, 179, 368, 376, 377, 379, 383, 394, 398, 399, 411, 412, 413, 439, 440, 449, 455, 456, 458, 478, 508, 533 Odds Ratio, 14, 55, 533, 548 Ointments, 533, 535 Oligosaccharides, 532, 533 Omega-3 fatty acid, 9, 317, 327, 533 Oncogene, 308, 310, 365, 369, 443, 516, 533, 546 Oncogenic, 520, 534, 540, 544 On-line, 310, 326, 477, 534 Opacity, 501, 534 Organ Specificity, 534 Ornithine, 534, 545 Osteoporosis, 407, 425, 534, 546 Ostomy, 406, 416, 534 Outpatient, 454, 456, 463, 534
Ovarian Cysts, 534, 544 Ovarian epithelial cancer, 347, 358, 534 Ovaries, 514, 534, 551 Ovary, 507, 534 Overall survival, 376, 395, 534 Overweight, 314, 411, 534 Ovum, 523, 534, 563 Oxaliplatin, 311, 323, 328, 330, 331, 343, 345, 349, 353, 355, 420, 450, 534 Oxidation, 386, 481, 486, 489, 500, 513, 524, 534 Oxidation-Reduction, 489, 534 Oxidative Stress, 534 Oxygenase, 535 P P53 gene, 381, 396, 400, 535 Paclitaxel, 310, 324, 337, 535 Palliative, 358, 535, 557 Palliative therapy, 358, 535 Pancreas, 481, 489, 502, 511, 515, 520, 535, 550, 554, 559, 560 Pancreatic, 347, 348, 352, 358, 443, 448, 494, 511, 535 Pancreatic cancer, 443, 535 Pancreatic Juice, 511, 535 Pancreaticoduodenectomy, 535 Pancreatitis, 415, 535 Papovaviridae, 535, 540 Paracoccidioidomycosis, 535 Paraffin, 364, 535 Paralysis, 356, 535 Parasitic, 488, 535 Parenteral, 505, 535 Parietal, 535, 537 Paroxysmal, 443, 535 Partnership Practice, 536, 542 Pathogenesis, 36, 368, 376, 394, 406, 407, 536 Pathologic, 46, 380, 396, 400, 486, 489, 499, 517, 536 Pathologic Processes, 486, 536 Pathophysiology, 51, 407, 536 Patient Compliance, 7, 8, 30, 536 Patient Education, 12, 54, 416, 453, 454, 457, 465, 472, 474, 479, 536 PDQ, 449, 450, 452, 536 Pelvic, 34, 416, 504, 536, 543 Pelvis, 26, 467, 481, 525, 534, 536, 560, 561 Penicillin, 337, 485, 536 Pentoxifylline, 310, 536 Pepsin, 536 Pepsin A, 536
576 Colon Cancer
Peptic, 411, 415, 536 Peptic Ulcer, 411, 415, 536 Peptide, 341, 373, 381, 386, 397, 483, 494, 505, 508, 523, 536, 543, 544, 546 Perceived risk, 25, 44, 536 Perception, 23, 29, 536, 550 Percutaneous, 537 Perforation, 38, 46, 411, 537 Perfusion, 518, 537 Pericardium, 537, 556 Periodicity, 537 Peripheral blood, 378, 520, 537, 541 Peripheral stem cell transplantation, 347, 537 Peritoneal, 307, 325, 502, 503, 521, 537, 544 Peritoneal Cavity, 521, 537, 544 Peritoneal Dialysis, 502, 503, 537 Peritoneum, 372, 382, 467, 528, 537 Peritonitis, 537 Petroleum, 535, 537 Pharmaceutical Preparations, 493, 511, 537 Pharmacists, 12, 51, 537 Pharmacokinetic, 329, 537 Pharmacologic, 484, 487, 537, 558 Pharynx, 511, 537 Phenotype, 176, 178, 538 Phenylalanine, 536, 538, 560 Phenylbutyrate, 538 Phosphodiesterase, 536, 538 Phospholipases, 538, 552 Phospholipids, 387, 508, 527, 538 Phosphorus, 337, 491, 538 Phosphorylated, 496, 538 Phosphorylation, 495, 538, 543 Phosphorylcholine, 495, 538 Photocoagulation, 496, 538 Photosensitization, 538 Physical Examination, 494, 538 Physical Fitness, 425, 538 Physician Assistants, 53, 538 Physiologic, 521, 527, 528, 538, 543, 547 Physiology, 4, 309, 407, 504, 511, 538 Pigmentation, 527, 538 Pigments, 489, 492, 538, 548 Pilot study, 32, 538 Pituitary Gland, 508, 539 Placenta, 507, 539 Plant Components, 313, 323, 539 Plant Growth Regulators, 514, 539 Plants, 483, 488, 491, 495, 512, 521, 523, 529, 538, 539, 540, 558, 559
Plasma, 21, 179, 313, 485, 493, 505, 508, 511, 512, 515, 531, 539, 544, 551 Plasma cells, 485, 531, 539 Plasmid, 511, 539, 561 Plasmin, 539 Plasminogen, 539 Plasminogen Activators, 539 Platelet Activation, 539, 552 Platelet Aggregation, 484, 532, 536, 539, 557 Platelets, 531, 532, 539, 557 Platinum, 495, 524, 534, 539 Platinum Compounds, 534, 539 Pleomorphic, 533, 539 Pneumonia, 499, 540 Point Mutation, 42, 540 Poisoning, 521, 531, 540 Polycystic, 443, 540 Polyethylene, 397, 540 Polymerase, 42, 540 Polymerase Chain Reaction, 42, 540 Polymorphic, 364, 495, 540 Polymorphism, 540 Polyomavirus, 535, 540 Polyp, 6, 7, 20, 27, 31, 33, 36, 41, 45, 47, 55, 380, 384, 385, 402, 455, 458, 467, 540 Polysaccharide, 486, 493, 540, 544 Polyunsaturated fat, 9, 540, 557 Portal Hypertension, 540 Portal Vein, 540 Positron emission tomography scan, 320, 540 Posterior, 484, 487, 535, 541 Postmenopausal, 15, 534, 541, 546 Postoperative, 313, 356, 365, 374, 454, 541 Postsynaptic, 541, 552 Potassium, 541 Potentiates, 521, 541 Potentiating, 541 Potentiation, 312, 330, 541, 552 Practicability, 541, 559 Practice Guidelines, 46, 441, 459, 460, 461, 541 Precancerous, 24, 27, 43, 364, 384, 455, 494, 507, 541 Precancerous polyps, 27, 455, 541 Preclinical, 33, 541 Precursor, 11, 33, 387, 487, 495, 503, 505, 508, 538, 539, 541, 542, 544, 559, 560, 561, 562 Predisposition, 49, 384, 401, 541 Preleukemia, 531, 541, 552
Index 577
Premalignant, 5, 15, 33, 39, 40, 47, 396, 413, 440, 456, 541 Preoperative, 42, 416, 454, 541 Prevalence, 19, 22, 26, 34, 43, 45, 55, 386, 406, 533, 541 Preventive Health Services, 32, 541 Preventive Medicine, 3, 4, 18, 23, 44, 473, 542 Primary Biliary Cirrhosis, 411, 542 Primary Prevention, 15, 20, 54, 406, 413, 542 Primary Sclerosing Cholangitis, 5, 18, 542 Primary tumor, 18, 365, 542, 551 Private Practice, 455, 542 Probe, 542 Proctitis, 407, 542 Proctocolectomy, 18, 542 Proctoscopy, 22, 542 Proctosigmoidoscopy, 36, 43, 542 Prodrug, 542 Prognostic factor, 381, 400, 542 Program Evaluation, 30, 542 Progressive, 5, 376, 394, 420, 467, 493, 495, 503, 506, 514, 530, 531, 539, 542, 560 Promoter, 308, 395, 542 Prone, 26, 542 Prophylaxis, 46, 542, 561 Proportional, 20, 511, 536, 542 Prospective Studies, 11, 376, 395, 542 Prospective study, 19, 51, 320, 542 Prostaglandin, 179, 378, 380, 387, 543, 557 Prostaglandins A, 387, 519, 543 Prostaglandins D, 543 Prostate, 177, 322, 349, 406, 421, 443, 489, 543, 560 Protease, 497, 543 Protein C, 23, 484, 488, 496, 508, 543, 559 Protein Conformation, 484, 543 Protein S, 366, 409, 444, 489, 512, 543, 549, 556 Protein-Tyrosine Kinase, 512, 543 Proteoglycans, 488, 507, 544 Proteolytic, 370, 387, 497, 505, 508, 539, 544 Prothrombin, 544, 557 Protocol, 18, 53, 376, 395, 449, 544 Protons, 483, 517, 522, 544, 545 Proto-Oncogene Proteins, 535, 544 Proto-Oncogene Proteins c-mos, 535, 544 Proto-Oncogenes, 380, 396, 400, 544 Proximal, 6, 12, 26, 29, 31, 36, 38, 39, 41, 45, 48, 51, 502, 544
Proxy, 544 Pseudomembranous Colitis, 47, 544 Pseudomyxoma peritonei, 467, 544 Psychic, 527, 544, 550 Psychoactive, 544, 562 Psyllium, 337, 338, 544 Puberty, 36, 544 Public Health, 17, 37, 401, 414, 441, 544 Public Policy, 437, 544 Pulmonary, 490, 499, 523, 545, 555, 561 Pulmonary Artery, 490, 545, 561 Pulse, 529, 545 Purgative, 523, 545 Purines, 488, 545, 551 Putrefaction, 545 Putrescine, 545 Pyogenic, 506, 545 Pyrimidines, 488, 545, 551 Q Quality of Life, 407, 408, 425, 535, 545, 555 R Race, 15, 29, 38, 522, 528, 545 Radiation therapy, 34, 365, 368, 375, 479, 482, 507, 521, 522, 545, 546, 563 Radioactive, 372, 382, 490, 517, 519, 521, 522, 524, 525, 529, 532, 534, 545, 546, 550, 551, 563 Radioactivity, 372, 382, 545 Radioimmunotherapy, 307, 310, 397, 545, 546 Radioisotope, 381, 397, 546, 558 Radiolabeled, 359, 522, 545, 546, 563 Radiological, 537, 546 Radiologist, 508, 546 Radiology, 35, 40, 358, 459, 546 Radiosensitization, 546 Radiotherapy, 378, 490, 522, 545, 546, 563 Raloxifene, 546, 550 Raltitrexed, 330, 546 Randomized clinical trial, 546 Randomized Controlled Trials, 40, 52, 405, 412, 546 Ras gene, 42, 546 Ras Proteins, 546 Reagent, 384, 385, 397, 547 Receptors, Serotonin, 547, 551 Recombinant, 388, 431, 520, 547, 561 Recombination, 498, 511, 512, 547 Recur, 537, 547 Red blood cells, 506, 531, 535, 547 Red Nucleus, 487, 547 Reductase, 50, 340, 373, 525, 528, 547, 557
578 Colon Cancer
Refer, 1, 7, 28, 497, 509, 510, 516, 524, 532, 545, 547, 558 Refraction, 547, 553 Refractory, 313, 329, 331, 349, 504, 547 Regeneration, 508, 547 Regimen, 16, 27, 330, 344, 347, 348, 353, 503, 536, 547 Regional chemotherapy, 547 Regional lymph node, 365, 377, 547 Registries, 20, 47, 463, 468, 547 Regression Analysis, 21, 47, 547 Regurgitation, 511, 548 Relapse, 25, 548 Relative risk, 17, 21, 29, 43, 548 Reliability, 31, 53, 381, 397, 548 Remission, 547, 548 Renal pelvis, 548, 559 Reproductive cells, 512, 516, 548 Reproductive History, 19, 548 Research Design, 548 Resection, 5, 53, 177, 459, 460, 548 Residual disease, 367, 372, 382, 548 Respiration, 491, 529, 548 Response rate, 28, 548 Retina, 493, 548, 549 Retinal, 548, 549 Retinal Vein, 549 Retinoblastoma, 443, 549 Retrospective, 4, 49, 549 Retroviral vector, 511, 549 Retrovirus, 549 Rheology, 536, 549 Ribonucleoproteins, 532, 549 Ribose, 549, 557 Ribosome, 549, 559 Rickets, 549, 562 Risk patient, 40, 49, 53, 324, 413, 455, 549 Rod, 506, 549 Rubber, 306, 481, 549 S Salicylate, 549 Salivary, 500, 502, 535, 549, 555 Salivary glands, 500, 502, 549 Sarcoma, 346, 549 Saturated fat, 9, 51, 549 Scans, 550 Schizoid, 550, 562 Schizophrenia, 386, 550, 562 Schizotypal Personality Disorder, 550, 562 Sclerosis, 443, 550 Secondary tumor, 528, 550
Secretion, 338, 387, 463, 506, 511, 516, 517, 520, 530, 550, 559 Sedimentation, 550, 560 Seizures, 486, 535, 550 Selective estrogen receptor modulator, 546, 550 Selenium, 4, 20, 309, 316, 550 Selenomethionine, 550 Semen, 543, 550 Semisynthetic, 491, 551 Semustine, 375, 551 Senescence, 330, 551 Senile, 534, 551 Sensitization, 551 Sentinel lymph node mapping, 551 Sequencing, 540, 551 Serine, 544, 551, 559 Serologic, 518, 551 Serotonin, 463, 532, 547, 551, 559 Serous, 505, 551 Serum, 312, 369, 371, 377, 378, 484, 497, 525, 537, 551, 560 Sex Characteristics, 544, 551, 556 Sex Determination, 443, 551 Shedding, 551 Shock, 551, 559 Side effect, 346, 352, 354, 366, 374, 375, 429, 431, 482, 489, 531, 551, 555, 558 Sigmoid, 29, 39, 175, 389, 403, 416, 454, 551, 552 Sigmoid Colon, 29, 39, 389, 403, 416, 551, 552 Sigmoidoscope, 21, 33, 38, 39, 46, 52, 542, 552 Signal Transduction, 311, 552 Signs and Symptoms, 548, 552, 560 Silymarin, 322, 529, 552 Skeleton, 522, 543, 552 Small intestine, 347, 352, 371, 389, 492, 494, 503, 517, 518, 521, 552, 559, 561 Smoldering leukemia, 531, 552 Smooth muscle, 30, 483, 484, 487, 498, 516, 552, 555 Sneezing, 551, 552 Social Environment, 545, 552 Social Security, 546, 552 Social Support, 32, 552 Socioeconomic Factors, 20, 552 Sodium, 308, 552, 553 Sodium Dodecyl Sulfate, 553 Soft tissue, 369, 490, 552, 553 Solid tumor, 345, 485, 489, 503, 524, 553
Index 579
Solvent, 513, 553 Soma, 553 Somatic, 6, 50, 368, 504, 517, 529, 553, 556 Somatic mutations, 6, 50, 368, 553 Somatomedins, 520, 553 Soybean Oil, 540, 553, 562 Specialist, 378, 409, 463, 468, 553 Species, 483, 490, 493, 496, 506, 517, 522, 528, 529, 535, 540, 545, 553, 562, 563 Specificity, 5, 22, 26, 30, 41, 42, 376, 377, 383, 395, 398, 399, 482, 541, 553 Spectroscopic, 533, 553 Spectrum, 44, 500, 553 Sperm, 495, 512, 516, 548, 553, 560 Sphincters, 508, 553 Spinal cord, 493, 495, 527, 531, 553 Spleen, 500, 517, 525, 553, 554 Splenic Vein, 540, 554 Staging, 36, 365, 391, 397, 406, 459, 465, 550, 554 Statistically significant, 38, 43, 52, 554 Stem cell transplantation, 347, 554 Stem Cells, 537, 554 Stent, 352, 534, 554 Steroids, 408, 512, 554 Stimulant, 516, 554 Stimulus, 503, 554 Stoma, 416, 534, 554 Stool test, 424, 554 Strand, 540, 554 Stress, 38, 478, 509, 531, 534, 541, 549, 554 Striatum, 533, 554 Stroke, 361, 425, 436, 492, 554 Stromal, 312, 331, 490, 504, 554 Styrene, 549, 554 Subacute, 519, 554 Subclinical, 519, 550, 554 Submaxillary, 506, 555 Substance P, 528, 550, 555 Substrate, 532, 555 Suction, 46, 555 Sulfates, 553, 555 Sulfides, 44, 555 Sulfur, 507, 528, 555 Sulindac, 322, 338, 555 Superoxide, 328, 555 Supine, 26, 555 Supplementation, 24, 307, 324, 325, 555 Support group, 454, 465, 478, 555 Supportive care, 536, 555 Suppression, 179, 312, 402, 501, 511, 555 Suramin, 555
Surfactant, 553, 555 Symphysis, 494, 543, 555 Symptomatic, 369, 535, 555 Synaptic, 532, 552, 555 Synergistic, 555 Systemic disease, 373, 383, 556 Systemic lupus erythematosus, 407, 556 T Tachycardia, 488, 556 Tachypnea, 488, 556 Taurine, 489, 494, 501, 524, 556 Telangiectasia, 443, 556 Telencephalon, 488, 494, 556 Telomerase, 556 Temozolomide, 556 Tenesmus, 47, 556 Terminal Care, 49, 556 Terminator, 496, 556 Testis, 507, 556 Testosterone, 547, 556 Tetracycline, 338, 556 Thalamic, 487, 556 Thalamic Diseases, 487, 556 Thalidomide, 324, 556 Therapeutics, 368, 395, 408, 430, 557 Thermal, 487, 532, 540, 557 Thioredoxin, 557 Thoracic, 487, 557, 562 Thorax, 481, 525, 557 Threonine, 544, 551, 557 Thrombin, 508, 539, 543, 544, 557 Thrombolytic, 539, 557 Thrombomodulin, 543, 557 Thrombosis, 520, 543, 554, 557 Thrombospondin 1, 557 Thromboxanes, 487, 503, 557 Thrombus, 499, 519, 531, 539, 557 Thymidine, 557 Thymidine Kinase, 557 Thymidine Phosphorylase, 557 Thymidylate Synthase, 176, 309, 312, 323, 329, 557 Thymus, 518, 525, 557 Thyroid, 332, 557, 560 Tin, 539, 558 Tissue Culture, 558, 562 Tolerance, 5, 6, 481, 512, 558 Tomography, 26, 498, 550, 558 Tone, 380, 558 Tonus, 558 Topical, 337, 517, 535, 558 Topoisomerase inhibitors, 522, 558
580 Colon Cancer
Toxic, v, 407, 483, 488, 494, 498, 500, 505, 514, 518, 545, 550, 554, 558 Toxicity, 16, 331, 503, 558 Toxicology, 307, 313, 328, 331, 438, 558 Toxin, 505, 558 Trace element, 413, 490, 558 Tracer, 326, 558 Trachea, 491, 537, 557, 558 Transcriptase, 381, 400, 549, 556, 558 Transcription Factors, 309, 324, 395, 558 Transduction, 552, 558 Transfection, 489, 511, 559 Transforming Growth Factor beta, 559 Transitional cell carcinoma, 559 Translation, 483, 559 Translational, 511, 559 Transmitter, 481, 526, 559, 561 Transverse Colon, 389, 403, 559 Trauma, 329, 417, 488, 507, 535, 556, 559 Treatment Outcome, 406, 559 Trees, 549, 559 Trisomy, 485, 559 Troglitazone, 559 Tropomyosin, 559 Troponin, 559 Trypanosomiasis, 555, 559 Trypsin, 505, 559 Tryptophan, 463, 496, 551, 559 Tubercle, 533, 559 Tuberous Sclerosis, 443, 560 Tubulin, 528, 560 Tumor marker, 406, 459, 489, 560 Tumor Necrosis Factor, 557, 560 Tumor suppressor gene, 381, 396, 400, 535, 560 Tumour, 178, 326, 385, 486, 560 Tunica, 530, 560 Tyrosine, 179, 364, 543, 560 U Ulcer, 387, 463, 536, 560 Unconscious, 501, 518, 560 Unresectable, 327, 342, 343, 344, 372, 382, 560 Uracil, 545, 560 Uraemia, 535, 560 Ureter, 548, 559, 560 Urethra, 543, 560 Urine, 342, 486, 490, 506, 515, 548, 560 Urokinase, 560 Ursodeoxycholic Acid, 561 Uterus, 456, 494, 504, 514, 527, 534, 561
V Vaccination, 561 Vagina, 494, 501, 514, 527, 561 Vascular endothelial growth factor, 313, 561 Vasculitis, 535, 561 Vasodilator, 491, 516, 532, 561 VE, 306, 561 Vector, 558, 561 Vein, 374, 521, 532, 540, 549, 554, 561 Venous, 515, 543, 561 Ventral, 533, 561 Ventricle, 492, 533, 545, 561 Ventricular, 561 Ventricular Function, 561 Venules, 490, 491, 505, 561 Verapamil, 561 Veterinarians, 12, 51, 561 Veterinary Medicine, 437, 561 Video Recording, 415, 561 Videodisc Recording, 561 Villi, 561, 562 Villous, 29, 45, 55, 562 Vimentin, 562 Vinblastine, 560, 562 Vincristine, 560, 562 Viral, 508, 534, 544, 549, 558, 562 Virtual colonoscopy, 5, 6, 7, 26, 28, 30, 34, 35, 455, 562 Virulence, 558, 562 Virus, 178, 422, 488, 505, 512, 520, 521, 540, 549, 558, 562 Viscera, 528, 553, 562 Visceral, 537, 562 Vitamin D, 306, 315, 332, 378, 408, 549, 562 Vitamin E, 19, 315, 320, 562 Vitro, 310, 313, 323, 326, 328, 331, 371, 378, 511, 515, 519, 540, 558, 562 Vivo, 322, 323, 326, 328, 403, 511, 515, 519, 555, 557, 562 W Wheezing, 463, 562 White blood cell, 350, 358, 481, 485, 514, 523, 525, 526, 529, 530, 531, 539, 562 Windpipe, 537, 557, 562 Withdrawal, 562 Womb, 561, 563 Wound Healing, 493, 508, 520, 526, 563 X Xenobiotics, 563 Xenograft, 324, 485, 563
Index 581
X-ray, 13, 455, 488, 490, 492, 498, 509, 510, 522, 530, 532, 545, 546, 550, 562, 563 X-ray therapy, 522, 563
Y Yeasts, 510, 521, 538, 563 Z Zymogen, 543, 563
582 Colon Cancer
