KIN ANCER A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
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 2003 by ICON Group International, Inc. Copyright 2003 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., 1960Skin 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: 0-597-83670-1 1. Skin 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.
Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail:
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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 skin 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 SKIN CANCER ........................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Skin Cancer................................................................................. 40 E-Journals: PubMed Central ..................................................................................................... 124 The National Library of Medicine: PubMed .............................................................................. 127 CHAPTER 2. NUTRITION AND SKIN CANCER................................................................................ 251 Overview.................................................................................................................................... 251 Finding Nutrition Studies on Skin Cancer................................................................................ 251 Federal Resources on Nutrition ................................................................................................. 255 Additional Web Resources ......................................................................................................... 255 CHAPTER 3. ALTERNATIVE MEDICINE AND SKIN CANCER ......................................................... 257 Overview.................................................................................................................................... 257 National Center for Complementary and Alternative Medicine................................................ 257 Additional Web Resources ......................................................................................................... 265 General References ..................................................................................................................... 270 CHAPTER 4. DISSERTATIONS ON SKIN CANCER ........................................................................... 271 Overview.................................................................................................................................... 271 Dissertations on Skin Cancer..................................................................................................... 271 Keeping Current ........................................................................................................................ 272 CHAPTER 5. CLINICAL TRIALS AND SKIN CANCER ...................................................................... 273 Overview.................................................................................................................................... 273 Recent Trials on Skin Cancer..................................................................................................... 273 Keeping Current on Clinical Trials ........................................................................................... 297 CHAPTER 6. PATENTS ON SKIN CANCER ...................................................................................... 299 Overview.................................................................................................................................... 299 Patents on Skin Cancer.............................................................................................................. 299 Patent Applications on Skin Cancer .......................................................................................... 351 Keeping Current ........................................................................................................................ 373 CHAPTER 7. BOOKS ON SKIN CANCER .......................................................................................... 375 Overview.................................................................................................................................... 375 Book Summaries: Federal Agencies............................................................................................ 375 Book Summaries: Online Booksellers......................................................................................... 377 The National Library of Medicine Book Index ........................................................................... 380 Chapters on Skin Cancer............................................................................................................ 382 CHAPTER 8. MULTIMEDIA ON SKIN CANCER ............................................................................... 409 Overview.................................................................................................................................... 409 Video Recordings ....................................................................................................................... 409 Bibliography: Multimedia on Skin Cancer ................................................................................ 411 CHAPTER 9. PERIODICALS AND NEWS ON SKIN CANCER ............................................................ 415 Overview.................................................................................................................................... 415 News Services and Press Releases.............................................................................................. 415 Newsletter Articles .................................................................................................................... 421 Academic Periodicals covering Skin Cancer .............................................................................. 422 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 423 Overview.................................................................................................................................... 423 U.S. Pharmacopeia..................................................................................................................... 423 Commercial Databases ............................................................................................................... 425 Researching Orphan Drugs ....................................................................................................... 425 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 431
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Contents Overview.................................................................................................................................... 431 NIH Guidelines.......................................................................................................................... 431 NIH Databases........................................................................................................................... 433 Other Commercial Databases..................................................................................................... 440 The Genome Project and Skin Cancer........................................................................................ 440 APPENDIX B. PATIENT RESOURCES ............................................................................................... 445 Overview.................................................................................................................................... 445 Patient Guideline Sources.......................................................................................................... 445 Associations and Skin Cancer.................................................................................................... 466 Finding Associations.................................................................................................................. 470 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 473 Overview.................................................................................................................................... 473 Preparation................................................................................................................................. 473 Finding a Local Medical Library................................................................................................ 473 Medical Libraries in the U.S. and Canada ................................................................................. 473
ONLINE GLOSSARIES................................................................................................................ 479 Online Dictionary Directories ................................................................................................... 481 SKIN CANCER DICTIONARY................................................................................................... 483 INDEX .............................................................................................................................................. 557
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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 skin 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 skin 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 skin 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 skin 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 skin 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 skin 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 SKIN CANCER Overview In this chapter, we will show you how to locate peer-reviewed references and studies on skin 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 skin 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 “skin 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: •
Early Detection and Treatment of Skin Cancer Source: American Family Physician. 62(2): 357-368. July 15, 2000. Contact: American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237 or (913) 906-6000. E-mail:
[email protected]. Website: www.aafp.org. Summary: This journal article provides health professionals with information on the early detection and treatment of skin cancer. The incidence of skin cancer is increasing by epidemic proportions. Basal cell cancer remains the most common skin neoplasm. This type of skin cancer may be classified as nodular, pigmented, cystic, sclerosing or morpheaform, superficial, or nevoid. Treatment of basal cell carcinoma with simple excision is generally curative. Squamous cell cancers may be preceded by actinic
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keratoses. These premalignant lesions are treated with cryotherapy, excision, curettage, or topical 5-fluorouracil. Squamous cell carcinoma, which is the second most common skin cancer, is usually the result of a high lifetime cumulative dose of solar radiation. Although squamous cell carcinoma is usually easily cured with local excision, it may invade deeper structures and metastasize. Aggressive local growth and metastasis are common features of malignant melanoma, which accounts for 75 percent of all deaths associated with skin cancer. Types of malignant melanoma include the superficial spreading type, nodular melanoma, lentigo maligna melanoma, and acral lentiginous melanoma. Early detection greatly improves the prognosis of patients with malignant melanoma. Although the differential diagnosis of pigmented lesions is challenging, the asymmetry, border irregularity, color variation, and diameter checklist and the sevenpoint checklist are helpful in determining which pigmented lesions require excision. Sun exposure remains the most important risk factor for all skin neoplasms. Thus, patients should be taught basic safe sun measures, including avoiding sun exposure during peak ultraviolet B hours, using sunscreens and protective clothing properly, and avoiding suntanning. 8 figures, 7 tables, and 32 references. (AA-M). •
Photodynamic Therapy Effective for Skin Cancer Source: Skin and Allergy News. 28(1):9; January 1997. Summary: This journal article for health professionals discusses the use of photodynamic therapy for the treatment of basal and squamous cell skin cancer. Deltaaminolevulinic acid, which is the only photodynamic drug available in topical form, penetrates the abnormal epidermis over basal and squamous cell carcinomas and forces tumor cells to produce heme until they deplete themselves of iron. Following iron depletion, protoporphyrin accumulates and the cancers photosensitize themselves. Exposure to red light at about 630 nm is used to ultimately kill the cancer cells. Blue or green light can be used effectively for superficial skin lesions.
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How To Prevent Skin Cancer Source: Patient Care. 30(11):108; June 1996. Summary: This patient information sheet lists and briefly explains seven ways to prevent skin cancer. Among the suggested tips are avoiding too much sun exposure, using sunscreen when in the sun, protecting children from the sun, avoiding tanning salons, and using proper eye protection that specifically protects the eyes from ultraviolet light.
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Be on the Lookout for Skin Cancer Source: AJN. 96(8):16 A, 16 C-16 D; August 1996. Summary: This journal article for health professionals provides guidelines for educating patients about avoiding damage from the sun that can cause skin cancer. Risk factors for developing skin cancer are outlined. The ABCD rule of skin assessment is explained. Features of basal and squamous cell carcinoma, melanoma, and actinic keratosis are presented. Components of a patient education session on skin cancer prevention are discussed, including providing patients with easy-to-follow instructions on skin selfexamination, offering suggestions for ways of protecting the skin from sun exposure, and suggesting ways to effectively use screening agents. 6 references and 5 figures.
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Guidelines for School Programs to Prevent Skin Cancer Source: Morbidity and Mortality Weekly Report (MMWR). 51(RR-4):1-22, April 26, 2002. Summary: This report provides guidelines to help schools develop and conduct programs to prevent skin cancer. Schools can play a substantial role in protecting students from unnecessary exposure to ultraviolet light, thereby reducing their future risk for skin cancer. A comprehensive school approach to skin cancer prevention includes policies, environmental change, educational curricula, family involvement, professional development, integration with health services, and evaluation. The exposure of youth to harmful ultraviolet radiation today contributes to their risk for skin cancer later in life. Unlike many diseases, skin cancer is primarily preventable. Schools, in partnership with community groups and other national, federal, state, and voluntary agencies, can develop, implement, and promote initiatives that help protect youth from ultraviolet exposure. Guideline 1 establishes policies that reduce exposure to ultraviolet radiation at school. Guideline 2 calls for an environmental change, to provide and maintain physical and social environments that support sun safety and that are consistent with the development of other healthful habits. Guideline 3 deals with education, stressing that students be provided with health education which increases the knowledge, attitudes, and behavioral skills needed to prevent skin cancer. Guideline 4 involves family members in skin cancer prevention efforts. Guideline 5 calls for including skin cancer prevention knowledge and skills in preservice and inservice education for school administrators, teachers, physical education teachers and coaches, school nurses, and others who work with students. Guideline 6 calls for complementing and supporting skin cancer prevention education and sun-safety environments and policies with school health services. The final guideline calls for an evaluation of the program periodically. These guidelines serve as a framework for such initiatives. 1 figure, 145 references.
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Skin Cancer Education Resources Source: Morbidity and Mortality Weekly Report (MMWR). 51(RR-4):18, April 26, 2002. Summary: This appendix to the Guidelines for School Programs to Prevent Skin Cancer provides a list of sources of skin cancer information and educational resources, including governmental agencies, volunteer organizations, medical associations, and corporations. It provides addresses, phone numbers, and Internet addresses for each of these resource locations.
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Use of Nonphysician Health Care Providers for Skin Cancer Screening in the Primary Care Setting Source: Preventive Medicine. 34(3):374-379, March 2002. Summary: Researchers conducted a survey of a random sample of physicians specializing in family practice and internal medicine to determine physician use and amenability to use of nonphysician health care providers to perform skin cancer screening in comparison with other cancer screening examinations. Of 1,363 eligible physicians who completed the survey, 631 (46 percent) reported that a nurse practitioner or physician assistant performed at least one type of cancer screening examination on their patients. Twenty-nine and 22 percent of all physicians reported nurse practitioners or physician assistants performing skin cancer screening, respectively. Family physicians were more likely to use nurse practitioners and physician assistants to perform these cancer screening examinations than were internists. Skin examinations were performed less frequently by nurse practitioners and physician assistants than
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were all other cancer screening examinations. Seventy-three to 79 percent of family physicians and 60 to 70 percent of internists were amenable to having a nonphysician health care provider perform one or more of these examinations. The researchers conclude that primary care physicians are currently utilizing nonphysician health care providers to perform cancer screening examinations and the majority of those surveyed are amenable to the use of these providers for such examinations. This suggests that one possible strategy for increasing skin cancer screening is through an expanded role of nonphysician health care providers. 3 tables, 45 references. •
Use of Tanning Devices and Risk of Basal Cell and Squamous Cell Skin Cancers Source: Journal of the National Cancer Institute. 94(3):224-226, February 6, 2002. Summary: Researchers conducted a population-based, case-control study of the risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) associated with tanning device use. The study group included 603 BCC case patients, 293 SCC case patients, and 540 control subjects. Participants were age 25 to 74 years and were residents of New Hampshire. Researchers interviewed study participants in person to obtain information on tanning device use, sun exposure history, sun sensitivity, and other risk factors for skin cancer. For participants who reported the use of a sun lamp or tanning bed, or patronizing a tanning salon, researchers asked their ages at first and last use. Participants who reported using tanning devices were more likely to be female, age 50 years or younger, to have a sun-sensitive phenotype, to have had more painful sunburns, and to have sunbathed more than four times a year. Any use of tanning devices was associated with odds ratios of 2.5 for SCC and 1.5 for BCC. Adjustment for history of sunburns, sunbathing, and sun exposure did not affect the results. Results indicate that the use of tanning devices may contribute to the incidence of nonmelanoma skin cancers. The researchers conclude that there is a need to further evaluate the potential risks of BCC and SCC that are associated with tanning lamp exposure. 2 tables, 17 references.
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Impact of the Basic Skin Cancer Triage Curriculum on Providers' Skills, Confidence, and Knowledge in Skin Cancer Control Source: Preventive Medicine. 34(2):144-152, February 2002. Summary: Researchers assessed the impact of a 2-hour Basic Skin Cancer Triage (BSCT) curriculum for primary care providers (PCP's) on barriers to skin cancer control activities. A group of 28 PCP's participated in the 2-hour training curriculum, and 23 completed surveys prior to and following the intervention. The BSCT curriculum is an educational intervention designed to increase the ability of PCP's to accurately and confidently triage skin lesions and counsel their patients about skin cancer. The intervention included lectures on skin cancer epidemiology, clinical characteristics and diagnosis, and prevention and counseling approaches. It also included instruction and role playing for patient counseling. A central focus was instruction in triage of skin lesions. Baseline and followup surveys assessed providers' confidence in skin cancer detection, attitudes toward and practice of total body skin examination, and skin cancer counseling and knowledge before and after participation in the BSCT curriculum. Skills in identifying lesions were evaluated by an examination using slides selected by a dermatology expert. Data analysis indicated that the ability to accurately diagnose and triage lesions improved significantly. The largest improvement in triage ability occurred in ability to appropriately reassure their patients about lesions. PCP's also had significant improvements in both knowledge of skin cancer control practices and
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confidence in ability to provide skin cancer preventive services. The BSCT algorithm is appended. 3 tables, 26 references. •
Screening for Skin Cancer: Sense or Nonsense? Source: Family Practice. 19(1):112-114, February 2002. Summary: The author examines the scope of the skin cancer problem, the record of past successes and failures in dealing with the disease, and what the likely outcome would be if the decision were made to engage seriously and aggressively in a systematic program of primary and secondary prevention of various skin cancers, most particularly melanoma. Evidence suggests that the current melanoma epidemic may not be real. Most of the increase in melanoma incidence is due to a substantial increase in the incidence of thin melanomas that may never be of any biological consequence. There are no controlled prospective studies demonstrating the cost-effectiveness of screening for skin cancer. According to the U.S. Preventive Services Task Force, present evidence is insufficient to recommend for or against routine screening for skin cancer using a totalbody skin examination. Recommendations to avoid sunlight might have adverse health consequences. The author concludes that in the absence of any compelling data, it is difficult to justify any intervention to screen for skin cancer. In the absence of such data, there is no clear idea of what a reasonable intervention should look like. Attention should be given to reasonable strategies to minimize unnecessary biopsies for benign lesions. 10 references.
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Should the Skin Cancer Examination Be Taught in Medical School? Source: Archives of Dermatology. 138(9):1201-1203, September 2002. Summary: Researchers surveyed fourth-year medical students at Boston University School of Medicine to assess the frequency of observation, training, and practice of the skin cancer examination during the spring of 1996 and 1997. The survey assessed (1) students' skill levels for performing skin examinations and counseling regarding sun protection practices; (2) number of times the students had observed skin examinations, were trained by a physician in skin cancer examination, or were trained for counseling patients about sun protection; and (3) whether the students had been taught cancer prevention in class. Results showed that (1) 223 of 302 students completed the survey; (2) 41 percent of respondents were women; (3) the mean age of respondents was 27.5 years; (4) 52 percent of the respondents reported being unskilled in skin cancer examination; (5) 28 percent had never observed a skin cancer examination, and 41 percent had observed only three or fewer examinations; and (6) 40 percent had received no training in skin cancer examination, and 46 percent had three or fewer sessions of training. Other results showed that (1) 35 percent had never performed a complete skin examination, and 40 percent had completed only five or fewer examinations; (2) 20 percent had never examined a patient for atypical moles, and 47 percent had done so only one to five times; (3) students who had any experience with a skin cancer examination were three times more likely to report being skilled in the examination; and (4) exposure to cancer prevention education through lectures, Integrated Problem courses, faculty discussions, and clinical rotations was also associated with higher selfreported skill levels. The researchers conclude that even brief additions of skin cancer examination to the current medical school curriculum would likely increase student exposure and skill levels. 4 tables, 12 references.
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Randomized Trial of Skin Cancer Prevention in Aquatics Settings: The Pool Cool Program Source: Health Psychology. 21(6):579-587, November 2002. Summary: Researcher conducted a randomized trial of the Pool Cool Program, a multicomponent skin cancer prevention program that was evaluated in 28 swimming pools in Hawaii and Massachusetts. The program was designed for children age 5 to 10 years, their parents, and lifeguards and aquatics instructors. The participating pools included municipal and suburban pools, YMCA pools, and military pools. Pools in the sun protection (SP) arm of the study received (1) staff training; (2) a series of sun-safety lessons; (3) onsite interactive programs; (4) provision of sunscreen, shade, and signage; and (5) promotion of sun-safe environments. Sites in the injury prevention arm of the study received a parallel program that included lessons and activities on (1) bicycle and rollerblading safety, (2) fire safety, (3) traffic and walking safety, (4) poisoning and choking prevention, and (5) playground safety. The main evaluation tool was a survey that parents completed for themselves and their children at the beginning of the summer and about 8 weeks later. Results showed that (1) 1,010 parent-child respondents were included in the analysis at baseline, and 842 at followup; (2) Massachusetts respondents were far more likely to be white, and were more highly educated, more affluent, and at higher risk for skin cancer; (3) parents in Hawaii practiced more desirable sun-protection habits at baseline and reported pools with more sun-safety policies, but Massachusetts parents had higher knowledge scores; and (4) children in Massachusetts were at higher risk than those in Hawaii, reported using more sun protection, and had no more sunburns than Hawaii youth. Effects of the Pool Cool Program showed that parent-child respondents in the SP arm showed (1) significantly improved use of sunscreen and shade, (2) overall improved sun-protection habits, (3) fewer sunburns, (4) improvements in parents' hat use and sun-protection habits, and (5) improvements in reported sun-protection policies and environments. The researchers conclude that the Pool Cool Program had significant positive effects at swimming pools in diverse audiences. 2 figures, 5 tables, 36 references.
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Can Internet-based Continuing Medical Education Improve Physicians' Skin Cancer Knowledge and Skills? Source: Journal of General Internal Medicine. 16(1):50-56, January 2001. Summary: Researchers evaluated an Internet-based continuing medical education (CME) program designed to improve physicians' skin cancer knowledge and skill. The program, Melanoma Education for Primary Care (MEPC), provides an interactive, customized learning experience that incorporates well-established guidelines for recognizing melanoma. The program was provided through a commercial CME Web Site and through linkage with a commercial Internet medical portal. To receive CME credit, users had to complete a test before and after viewing the program. The tests were identical and consisted of 32 questions. Seven questions addressed confidence and attitudes (opinions), 10 rated general skin cancer knowledge, and 15 evaluated responses to clinical vignettes. In the vignettes, users were shown a picture of a lesion along with a brief clinical history and asked to decide whether the lesion should be biopsied or not. Of 691 Internet users who took the pretest, 354 stated that they were physicians and completed the entire program and posttest, and requested CME credit. This group was used as the study population in this analysis. Self-reported data on experience in dermatology revealed that 4 percent of the users had no dermatology training, 41 percent had received medical school lectures in dermatology, 24 percent had a residency or had received postgraduate dermatology lectures, 29 percent had
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experienced a rotation on a dermatology service, and 2 percent had completed a dermatology residency. Most (65 percent) of the users were in active primary care practice. After viewing MEPC, the physicians felt much more confident in their abilities to manage pigmented lesions, including melanoma. They showed generally more positive attitudes toward the role of primary care physicians and assessing the risk of skin cancer. Associated with improvements in confidence, users showed significant improvements in skin cancer knowledge after viewing the program, the overall percentage of correct answers increasing from 52 percent on the pretest to 85 percent on the posttest. Physicians in dermatology practice showed the highest pretest and posttest scores, 76 and 90 percent. Eighty-one percent of the vignettes were answered correctly on the pretest and 90 percent were answered correctly on the posttest. User satisfaction with the program was rated as extremely high. Researchers conclude that an easily distributed, online program can improve physician confidence and knowledge and, possibly, skills in managing skin cancer. This type of program could be beneficial because lack of confidence in identifying suspect lesions is a major barrier to primary care physicians performing skin cancer screening. 1 figure, 2 tables, 17 references. •
Skin Cancer Primer for Primary Care Source: Journal of the American Academy of Physician Assistants. 14(4):13-26, April 2001. Summary: The author presents basic information on skin cancer for primary health care providers. It is one of a series of articles approved for category one continuing medical education (CME). The article (1) summarizes the epidemiologic aspects of the three types of skin cancer (basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma); (2) discusses ultraviolet radiation and other risk factors for skin cancer; and (3) presents clinical guidelines for diagnosing BCC, SCC, and melanoma. The article also summarizes guidelines to assist health care providers in counseling patients on skin cancer prevention. 3 figures, 14 references.
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Reducing Skin Cancer Risk: An Intervention Based on Protection Motivation Theory Source: Journal of Health Psychology. 6(3):321-328, May 2001. Summary: Researchers investigated the effectiveness of a brief skin cancer prevention intervention based on protection motivation theory (PMT). The intervention targeted skin appearance and included brief lectures, video clips about a young man who had died of melanoma, a comprehensive essay, and brief discussions. Participants included 58 white college students who had tanned intentionally at least one time in the past year. The students were randomly assigned to either the wait-list control group or the intervention group. A self-report questionnaire was used to assess variables (e.g., vulnerability and behavioral intention) in the PMT model at pretest, posttest, and followup. Researchers also took photographs immediately following the intervention, and 1 month later to assess compliance with the intervention. Data analysis indicated that the PMT-based intervention was effective in changing participants' attitudes and behaviors associated with skin cancer risk. Comparison of the photographs indicated that 72 percent of the participants had lighter skin, while 16 percent had darker skin at followup. The researchers conclude that theory-based methods for changing maladaptive attitudes and behaviors related to skin cancer risk are effective. 1 figure, 2 tables, 16 references.
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Skin Cancer Prevention Research Receives National Award Source: Hawaii Medical Journal. 60(5):128, 135, May 2001. Summary: Skin cancer prevention research has been a major focus in the Prevention and Control Program at the Cancer Research Center of Hawaii. Recently, a major skin cancer prevention research project, Pool Cool, at the Center received an award of excellence from the American Academy of Dermatology. Pool Cool promotes skin cancer prevention at swimming pools. It is a multicomponent educational and environmental intervention that targets children age 5 to 10 years and their families and lifeguards. It was evaluated at pools in Hawaii and Massachusetts. Results showed significant positive changes in children's use of sunscreen and shade, overall sun protection habits, and reported sun protection policies. The results also highlighted a significant reduction in children's sunburns compared to the previous summer. Pool Cool is an extension and adaptation of the Hawaii SunSmart program. Hawaii SunSmart began in 1994 and was evaluated at 14 recreation sites on the island of Oahu. Designed for children age 6 to 8 years and their parents and recreation leaders, it provided training for staff, on-site activities, and interactive take-home booklets. Evaluation of the process and its shortterm impact indicated that parents, children, and staff had short-term improvements in knowledge, sun protection habits, readiness to change, sun protection policies, and sun protection norms. The Center's project SCAPE (Skin Cancer Awareness, Prevention, and Education) evaluates the impact of tailored, mailed interventions, such as risk feedback on the skin cancer prevention and skin self-examination behaviors of high-risk and moderate-risk adults and children in grades one through three. The project will evaluate tailored interventions in two diverse regions (Hawaii and Long Island, New York). Evaluation to date shows that tailored materials are rated more favorably than are standard materials. The tailored materials group reported improved sun protection habits, greater perceived benefits of sun protection, and trends toward improved knowledge, better sunscreen application, and higher perceived risk for skin cancer. 8 references.
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Impact of the Basic Skin Cancer Triage Curriculum on Providers' Skin Cancer Control Practices Source: Journal of General Internal Medicine. 16(5):302-307, May 2001. Summary: Researchers investigated the impact of a 2-hour, multicomponent educational intervention on the reported skin cancer control practices of primary care providers. The intervention was a 2-hour curriculum that supplemented provider skin cancer control practices through instruction in basic skin cancer triage (BSCT) and a brief summary of skin cancer epidemiology, prevention, and counseling. A convenience sample of 22 providers from a staff-model health maintenance organization participated in a 2-hour training session. Providers included physicians, nurses, and physician assistants from internal and family medicine departments. Before and after the intervention, researchers evaluated providers' attitudes and self-reported skin cancer control practices (e.g., performance of total body skin examination and counseling about skin cancer). The practice of skin cancer control behaviors during an initial visit with new patients and routine visits with patients at high risk for melanoma were also investigated. Provider practices were independently evaluated via exit interviews with patients of each of the providers. Data analysis indicated that following participation in the curriculum, providers' attitudes toward total body skin examination improved significantly, although their attitudes toward skin cancer prevention counseling did not improve. There were significant increases in provider self-reported skin cancer control practices during initial visits with new patients and routine visits with patients at high risk for
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melanoma. The patient exit interviews confirmed these changes in practice patterns. The researchers conclude that the BSCT curriculum is useful in increasing primary care providers' use of skin cancer control measures. 5 tables, 9 references. •
Skin Cancer Control in the Primary Care Setting: Are We Making Any Progress? (Editorial) Source: Journal of General Internal Medicine. 16(5):342-343, May 2001. Summary: The author notes that primary care physicians are in an ideal position to implement both skin cancer prevention and early detection into their practices. However, research shows that they perform skin examinations much less frequently than other screening examinations. Lack of evidence about this screening's success and lack of consensus about screening recommendations contribute to less frequent performance of skin cancer control practices by primary care physicians. Also, physicians tend to have little training for or confidence about performing the procedure. Finally, physicians may be targeting their skin cancer control practices only to patients with risk factors for skin cancer. Documenting the frequency of skin cancer control practices by primary care physicians may be important in establishing benchmarks for future comparisons. It is important to improve physicians' skin cancer control practices by increasing the frequency of such behaviors and improving the targeting of these practices to patients who will benefit the most. Physicians must receive help in improving their skills and accuracy in screening, diagnosis, and triaging of skin lesions suspicious for skin cancer. Research suggests that skin cancer control training programs can increase the frequency of skin cancer screening and education by primary care physicians and improve their skin cancer control attitudes. 18 references.
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About the Skin Cancer Foundation Source: Primary Care and Cancer. 21(5):9, May 2001. Summary: This article summarizes the activities of the Skin Cancer Foundation (SCF). The SCF is the only national and international organization concerned solely with skin cancer. A nonprofit foundation, it conducts public and medical education programs and provides support for medical training and research to help reduce the incidence, morbidity, and mortality of skin cancer. The SCF provides materials for primary care practitioners to use in increasing the awareness of patients for preventing, detecting, and treating skin cancer. A major goal of the SCF is to increase public awareness of the importance of taking preventive measures against sun exposure and to teach people how to recognize and act on the first warning signs of skin cancer. The SCF provides information to the public through a variety of ways including (1) promoting skin selfexamination in a nationwide campaign; (2) promoting sun-protective behaviors through broad-based public initiatives; (3) distributing publications about protecting children from sun exposure to schools, physicians offices, and camps; (4) providing information on melanoma; (5) providing audiovisual materials to physicians' offices and waiting rooms, schools, and community and corporate education programs; and (6) publication of the Skin Cancer Foundation Journal and a quarterly newsletter. The SCF also provides melanoma education to practitioners through the Melanoma Letters and funds basic research programs, clinical studies, and various skin cancer educational programs.
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Primary Prevention of Skin Cancer Offers Value for Money Source: Primary Care and Cancer. 21(5):40-42, May 2001.
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Summary: The author discusses primary prevention as an effective means of preventing skin cancer. The discussion focuses on a prevention campaign, SunSmart, conducted in Victoria State, Australia. SunSmart is based on the proposition that reducing exposure to sunlight as early as possible during childhood and maintaining that practice throughout life is the best approach for preventing skin cancer. Australia's experience with this program can be considered unique because skin cancer is more prevalent there than elsewhere. SunSmart and other programs have been implemented at both a state and national level. They consist of the following components: (1) A comprehensive educational strategy that focuses on sun protection policies and practices; (2) structural changes, including removal of the tax on sunscreens, and the development and implementation of sun protection guidelines for outdoor workers and sports enthusiasts; and (3) obtaining sponsors for promoting sun protection activities at tennis, cricket, surfing, and other outdoor sports events. Evaluation of SunSmart programs in the state of Victoria has revealed that substantial changes in behaviors and attitudes have occurred, particularly with regard to suntans. At least 60 percent of the residents of Victoria now say they have no desire for a suntan. Recent epidemiologic studies on the incidence of both melanoma and nonmelanocytic skin cancers in Australia have shown leveling off and, in some cases, decreases in the youngest age groups. A costeffectiveness analysis of SunSmart has shown the program to be effective. 11 references. •
Tailoring Messages and Design in a Web-based Skin Cancer Prevention Intervention Source: International Electronic Journal of Health Education. 4:290-297, 2001. Contact: INTERNET/EMAIL: http://www.iejhe.org/TOC/4/index/html. Summary: A researcher conducted an evaluation of a tailored web-based skin cancer prevention intervention. The tailored web page was based on constructs of social learning theory and incorporated messages that focused on participants' expected outcomes of regularly using or not using sunscreen and their perceived self-efficacy to regularly use sunscreen during high-risk exposure behaviors. Additional tailored messages addressed participants' skin cancer risk based on (1) their self-identified skin tone, (2) their specific high-risk sun exposure behaviors, (3) barriers to wearing sunscreen, (4) perceived risk of skin cancer, and (5) perceived personal involvement with the issue of skin cancer. All messages were written from the point of view of a source that participants selected from a number of choices at baseline, and a gendermatched photograph of the source was included on the web page adjacent to the messages. Participants also selected the headline fonts and colors that appeared on their tailored web page. The 110 participants were recruited from eight undergraduate classes at a large southeastern university; of these, 102 completed the baseline survey and 84 completed the posttest survey, 4 weeks later. When assessing their own skin types, 12 percent reported that they burn easily, 35 percent that they burn moderately, 29 percent burn minimally, and 24 percent that they rarely or never burn. At baseline, 19 percent of the participants reported that they never or rarely think about protecting their skin, 34 percent sometimes think about protecting their skin, and 47 percent think about skin protection every day. After random assignment, 47 participants received the tailored web page (treatment group) and 36 received the generic web page (comparison group). The most common target behavior of the participants in the treatment group was playing sports, followed by sunbathing, exercising, yard work, and swimming. The most commonly preferred message source selected by treatment group participants at baseline was a dermatologist (83 percent), followed by a skin cancer patient (11 percent), a parent (4 percent), and an older person (2 percent). Most (67 percent) picked blue as the color for their messages. Simple sans-serif font face was picked by the overwhelming
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majority (89 percent) of the participants. A significantly higher percentage of participants in the treatment group reported reading the information on their web page than did the comparisons, 81 versus 61 percent. Participants in the treatment group reported a greater preference for the message source than the comparisons. Significantly more treatment group participants reported following one or more of the links from their web page than the comparisons, 29 versus 13 percent. Treatment group participants reported that their web page had a higher degree of personalization than did comparison group participants; however, the comparisons reported that their web page had a higher degree of relevance. No significant differences were found between the two groups at posttest for (1) sunscreen wearing behaviors, (2) self-efficacy for wearing sunscreen, and (3) expected outcomes of wearing or not wearing sunscreen. Participants in the treatment group were less likely than comparison group participants to report that it was very important for them to acquire a tan and that they feel more attractive when they are tan. The researcher concludes that web-based tailoring may hold promise for promoting skin cancer prevention. 31 references. •
At Work With the CDC: A Course of Action on Skin Cancer Source: Business and Health. 19(4):40, April 2001. Summary: The author recommends that businesses work to help prevent skin cancer among their employees. Outdoor work and leisure can be potentially expensive for employers because of increased medical and other costs related to skin cancer. Prevention is the key to skin cancer. Employers can take several steps to help prevent skin cancer among their employees at a minimal cost. This can include (1) reducing exposure to ultraviolet (UV) light by revising work processes or tasks that put employees at risk; (2) reengineering equipment or tools used; (3) reorganizing work practices; and (4) providing and urging employees to use personal protective equipment, such as protective clothing. These steps all need worker education in order to succeed. Educational Campaigns are particularly appropriate during May, which is National Melanoma/Skin Cancer Detection and Prevention Month. The Centers for Disease Control and Prevention has a National Skin Cancer Education Program that features the national Choose Your Cover campaign. Through it, businesses can order free campaign materials for educating and encouraging employees to protect themselves against UV light. Materials such as posters, brochures, and radio public service announcements can be viewed, downloaded, and ordered on the World Wide Web.
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Screening for Skin Cancer: Recommendations and Rationale Source: American Journal of Preventive Medicine. 20(Supplement 3):44-46, April 2001. Summary: This statement summarizes the U.S. Preventive Services Task Force (USPSTF) recommendations for screening for skin cancer, and provides supporting scientific evidence. Evidence is insufficient to recommend for or against routine screening for skin cancer using a total body skin examination for the early detection of cutaneous melanoma, basal cell cancer, or squamous cell skin cancer, according to the USPSTF. Even in high-risk patients, benefits from screening are unproven. Clinicians should remain alert for skin lesions with malignant features noted in the context of physical examinations performed for other purposes. The USPSTF did not examine the outcomes related to surveillance of patients with familial syndromes, such as familial atypical mole and melanoma syndromes. Studies of skin health behaviors and studies of factors associated with advanced melanoma suggest that older persons are at high risk and are unlikely to benefit from existing skin cancer prevention efforts, such as public education and clinician education efforts regarding sun avoidance and/or sun protection. Since
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most elderly individuals consult a clinician at least yearly, case finding by clinicians focusing on the elderly may reach vulnerable individuals who may not benefit from other approaches. 9 references. •
Screening for Skin Cancer Source: American Journal of Preventive Medicine. 20(Supplement 3):47-58, April 2001. Summary: Researchers reviewed the literature on the effectiveness of routine screening for skin cancer by a primary care provider as part of an assessment for the U.S. Preventive Services Task Force. They included studies if they contained data on yield of screening, screening tests, risk factors, risk assessment, effectiveness of early detection, or cost-effectiveness. The following descriptive information was abstracted from fulltext published studies of screening: (1) Type of screening study, (2) study design, (3) setting, (4) population, (5) patient recruitment, (6) screening test description, (7) examiner, (8) advertising targeted at high-risk groups or not targeted, (9) reported risk factors of participants, and (10) procedure for referrals. The yield of screening data was also abstracted including (1) probabilities and numbers of referrals, (2) types of suspected skin cancers, (3) biopsies, (4) confirmed skin cancers, and (5) stages and thickness of skin cancers. Results of the review indicated that no randomized or case/control studies have been done demonstrating that routine screening for melanoma by primary care providers reduces morbidity or mortality. Researchers conclude that the quality of the evidence addressing the accuracy of routine screening by primary care providers for early detection of melanoma or nonmelanoma skin cancer ranged from poor to fair. No studies were found that assessed the effectiveness of periodic skin examinations by a clinician in reducing melanoma mortality. Both selfassessment of risk factors or clinician examination can classify a small proportion of patients at highest risk for melanoma. Skin cancer screening, perhaps using a risk assessment technique to identify high risk patients who are seeing a physician for other reasons, merits additional study as a strategy to address the excess burden of disease in older adults. 1 figure, 2 tables, 83 references.
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Impact of Skin Cancer Prevention on Outdoor Aquatics Staff: The Pool Cool Program in Hawaii and Massachusetts Source: Preventive Medicine. 33(3):155-161, September 2001. Summary: Researchers examined the effectiveness of a skin cancer prevention program for outdoor aquatics workers. The program, Pool Cool, was based on reducing sun exposure among outdoor aquatics staff and was implemented at 28 outdoor pool sites, 14 in Hawaii and 14 in Massachusetts, during 1999. The sites were randomized into eight sun protection (SP) and six child injury prevention (IP) sites in Hawaii and seven SP and seven IP sites in Massachusetts. The SP pools were the intervention sites and the IP pools were the control sites. The program targeted children age 5 to 10 years, their parents, and lifeguards and aquatics instructors; the swimming pool was the unit of randomization and intervention. The components of Pool Cool consisted of (1) a lifeguard/aquatic instructor training module; (2) Leader's Guide, a curriculum focusing on general injury prevention and related activities; (3) an eight-lesson curriculum on sun safety to be presented by aquatics instructors in their classes; (4) interactive activities on sun protection with children age 5 to 10 years; (5) sunscreen dispensers provided at the pool; and (6) incentives such as sunscreens and hats provided to aquatics staff. SP pools also received environmental supports, including shade structures and signs that provided sun protection tips. Training focused on (1) types of skin cancer and key sun protection messages; (2) appropriate sun protection methods; (3) teaching children
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about the importance of sun protection and avoiding sunburns, and using sun protection daily; and (4) motivating lifeguards to be role models for children. At the IP pools, aquatics staff received the Leader's Guide and a related training module. No environmental supports promoting sun protection were provided. The program was evaluated by having aquatics staff complete questionnaires assessing changes in sun protection habits, sunburning rates, and pool protection at baseline and at the end of the intervention, 6 to 8 weeks later. Altogether, 220 aquatics staff completed the baseline questionnaire and 194 completed the posttest questionnaire. At baseline about 50 percent had a history of severe sunburn and almost 80 percent had at least one sunburn the previous summer. When compared with staff at IP pools, sun protection policies and sunburning rates among the staff at SP pools significantly improved. There were no significant differences in sun protection behaviors between SP and IP pools. These outcomes were similar at both the Hawaii and Massachusetts sites. Researchers conclude that Pool Cool had significant effects on lifeguards and aquatics staff's sunburning rates and pool sun safety policies, but did not improve reported sun protective behaviors. More intensive intervention strategies may be needed to influence aquatics workers who have already begun to adopt skin cancer prevention policies. 2 tables, 22 references. •
Using Nurse Practitioners for Skin Cancer Screening: A Pilot Study Source: American Journal of Preventive Medicine. 21(3):214-217, October 2001. Summary: Researchers evaluated the ability of trained nurse practitioners to accurately identify suspicious skin lesions in a clinical setting. They identified five nurse practitioners who had no previous experience in evaluating skin lesions. Each nurse practitioner participated in a training program for skin cancer detection consisting of a workshop, clinical apprenticeship, and didactic lectures. Researchers assessed the nurse practitioner's ability to distinguish benign and malignant lesions using clinical color slides. The sensitivity of all five nurse practitioners to refer benign and malignant lesions for dermatological followup based on the slides was 100 percent, whereas the specificity ranged from 53 to 100 percent. Each nurse practitioner evaluated approximately 25 different patients along with a single dermatologist. The nurse practitioners' ability to correctly refer patients with suspicious lesions for dermatological followup was determined based on the dermatologist's assessment of need for referral. Results suggested a referral sensitivity and specificity ranging from 67 to 100 percent and 62 to 100 percent, respectively. Two dermatologists and four nurse practitioners independently examined 30 patients. The nurse practitioners' sensitivity for detecting significant skin cancer lesions ranged from 50 to 100 percent and the detection specificity was 99 to 100 percent when the consensus clinical diagnosis of the dermatologists was used as the gold standard. The researchers conclude that these preliminary results suggest that nurse practitioners can be trained to accurately identify and triage suspicious lesions. 1 table, 36 references.
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Public Health Responses for Skin Cancer Prevention: The Policy Framing of Sun Safety in Australia, Canada and England Source: Social Science and Medicine. 53(9):1175-1189, 2001. Summary: Researchers examined national differences in public health policies using case studies of Sun Safety Programs in Australia, Canada, and England. They used expert interviews and an evaluation of policy documents and press releases from the three countries to obtain data. Australia has the most well-developed and successful Sun Safety programs in the world. Skin cancer first became recognized as a public health
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problem in Australia in the 1950's. Sun Safety in Australia has communicators that are specialists in marketing, community development, and health promotion, and, therefore, are able to frame sun safety in the broad context of public activity. Skin cancer prevention and Sun Safety first appeared on the general Canadian public health agenda in 1990. Unlike Australia, Sun Safety in Canada has no single, central home, nor do programs have a central funding source. Sun Safety efforts in England are relatively new. Skin cancer was first noted as a public health problem in the late 1970's and early 1980's in England. Results indicate that a public health issue identified at the global scale can be framed differently in each country based upon specific social, cultural, and political situations. This study provides an example of how health policy is defined, constrained, and limited through the process of problem identification and policy resolution. The researchers conclude that framing and narrative analyses are powerful tools for understanding the place-specific implementation of public health policies and initiatives. 1 table, 75 references. •
Nonmelanoma Skin Cancer: Today's Epidemic Source: Texas Medicine. 97(2):56-58, February 2001. Summary: In this special issue on what primary physicians need to know about cancer, the author discusses the early diagnosis and treatment of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Nonmelanoma skin cancer is the most common cancer in the United States, and BCC and SCC account for most of these tumors. BCC constitutes about 75 percent of nonmelanoma skin cancers. BCC occurs more often in men and in the seventh decade of life, usually in the head and neck region. Risk factors for BCC include (1) genetic predisposition, (2) ultraviolet radiation exposure, (3) radiation therapy, (4) arsenic exposure, and (5) immunosuppression. Early diagnosis is important to reduce the morbidity associated with BCC. BCC usually presents as nodule-ulcerative, telangiectatic ivory papule, or plaque. Treatment usually involves surgery to remove these narrow strands of invasive tumor. SCC is the second most common nonmelanoma skin cancer, accounting for about 20 percent of cases. SCC also occurs more often in men and in the seventh decade of life, usually in the head and neck region. Risk factors for SCC include genetic predisposition, ultraviolet radiation exposure, immunosuppression, chemical carcinogens, and a history of chronic sun exposure. SCC usually presents as an ulcerated nodule with an indurated, elevated, red border. Treatment of SCC involves surgery to remove the nodules. The author concludes that (1) as the elderly population in the United States continues to increase, the incidence of nonmelanoma skin cancer will increase; and (2) early detection and diagnosis are the keys to improving cure rates. 19 references.
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Interactive Computer Technology for Skin Cancer Prevention Targeting Children Source: American Journal of Preventive Medicine. 18(1):69-76, January 2000. Summary: Researchers developed and evaluated a new multimedia computer program for the primary prevention of skin cancer among a childhood population. An interactive CD-ROM program was developed, then pilot tested in a public elementary school in rural North Carolina. This intervention trial involved eight third and fourth grade classes, numbering 209 students, randomized into three groups: (1) Computer intervention, (2) standard teacher-led intervention, and (3) controls. Students were tested using pre- and postintervention surveys that measured knowledge, attitudes, and self-reported behaviors. A 7-month followup survey was performed. The findings indicated there was a significant increase in postintervention knowledge for the computer group when compared to either the teacher-led or control groups. Attitudes
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about suntanning demonstrated a significant difference between the three groups. There were slight improvements in the behavioral scores, especially among the computer group, but the overall differences were not significant. Similar overall results were found for the long-term followup survey, except that attitudes about suntanning no longer demonstrated a significant difference. The authors suggest that this new educational tool is an effective way to introduce health education programs for young children in typical classroom settings. This prototype may serve as a model for the development of future preventive school-based programs, including applications to other conditions associated with high-risk behaviors among children. 3 tables, 36 references. •
Prevention of Nonmelanoma Skin Cancer (Editorial) Source: Archives of Dermatology. 136(2):245-246, February 2000. Summary: The authors discuss the prevention of nonmelanoma skin cancers (NMSC's). NMSC's are the most commonly occurring malignant neoplasms in the United States. Causal factors include ultraviolet (UV) radiation, ionizing radiation, and arsenic exposure. There is no proven strategy for preventing any type of skin cancer. Sunscreen use may reduce the risk of squamous cell carcinoma, but it may actually encourage sun exposure. Sun exposure in the first few decades of life may be the most significant causal factor. Avoidance of sun exposure and use of protective clothing should help prevent NMSC. Agents that have been evaluated for a possible protective role in skin cancer include 13-cis-retinoic acid, selenium, and beta carotene. Randomized controlled trials of 13-cis-retinoic acid and selenium found no evidence for a protective effect against NMSC. Early animal studies showed that beta carotene prevented UV light- and chemically-induced tumors of the skin. Two randomized controlled trials on beta carotene showed that it did not protect against NMSC. Three large trials have shown that beta carotene has at best no effect on cancers of the respiratory tract, and at worst increases risk. Secondary analysis of data from the Physicians Health Study confirm prior findings of a lack of efficacy of beta carotene in preventing NMSC. Results from trials of beta carotene for cancer prevention should raise issues for scientists who wish to base health recommendations on epidemiological or laboratory data. Regarding NMSC, published data from animal studies show that beta carotene has a protective effect, but epidemiological data do not support this. The authors conclude that one must rely on data from randomized controlled trials as the standard of proof for making clinical recommendations. 21 references.
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Sunscreens, Skin Photobiology, and Skin Cancer: The Need for UVA Protection and Evaluation of Efficacy Source: Environmental Health Perspectives. 108(Supplement 1):71-78, March 2000. Summary: The author reviews (1) the effects of ultraviolet-A (UVA) on the skin, (2) sunscreens, and (3) skin photobiology. Methods proposed for the evaluation of candidate sunscreen formulations of UVA protective ability are discussed. Topics include (1) DNA damage by UVA, (2) animal models, (3) synergistic effects of ultraviolet-B (UVB) and UVA, (4) pigmentation effects, (5) skin cancer, (6) immune suppression, (7) action spectrum for photoelastosis, (8) sunless tanning, (9) beneficial effects of ultraviolet radiation exposure, (10) durability and photostability issues of sunscreens, (11) UVA protection in current products, (12) progressive warning labels, and (13) areas for research on screens. Sunscreen product labels need to provide the consumer with more information. The author proposes that SPF (sun protection factor)
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be renamed sunburn protection actor, and that critical wavelength be designated as long wave index. 1 figure, 3 tables, 112 references. •
Association of Surface Ultraviolet B Radiation Levels With Melanoma and Nonmelanoma Skin Cancer in United States Blacks Source: Cancer Epidemiology, Biomarkers and Prevention. 9(3):291-297, March 2000. Summary: Researchers examined associations between surface ultraviolet B (UVB) radiation levels and melanoma and nonmelanocytic skin cancer (NMSC) in United States blacks. The impetus for the study was indications that geographical variations in relative skin cancer rates in blacks approached that of whites in the United States. Investigators extracted data on the incidence of melanoma in blacks and whites from the Surveillance, Epidemiology, and End Results (SEER) dataset for the period 1973 to 1994. Data on the number of black deaths from melanoma and NMSC for the period 1970 to 1994 were obtained for 506 state economic areas (SEA) in the 48 continental states. Information on UVB radiation reaching the surface (ground) level in the SEER area was obtained from measurements taken by Robertson/Berger meters at National Weather Service stations. For SEA's, similar data obtained for the District of Columbia and separate regions of northern and southern California were used. Associations between the cancer incidence and mortality data and the UVB measurements were assessed by Poisson regression techniques. For black males, mortality from melanoma associated with a 50 percent increase in surface UVB radiation was significantly increased, the ageadjusted relative risk (RR) and its 95 percent confidence interval (CI) being 1.16 (CI 1.021.32). The corresponding RR for NMSC during the period 1970 to 1981 (a time period chosen to avoid AIDS-related deaths from Kaposi's sarcoma) was 1.18 (CI 1.00-1.39), a nearly significant increase in risk. The nearly significant increase in NMSC mortality disappeared, however, when the data for 1970 to 1981 were combined with data for 1987 to 1994 that supposedly excluded AIDS-related deaths. For black females, the RR of mortality from melanoma was not significantly elevated either for melanoma or NMSC. The incidence of melanoma was not significantly associated with UVB radiation for either black males or females. Incidence data on NMSC were not available. Researchers concluded that the results of this study suggest that sunlight exposure increases the risk of skin cancer in blacks. The public health implications of this finding are uncertain because the absolute risk of skin cancer in blacks is much lower than in whites. This means that care must be exercised in fashioning recommendations for prevention, such as use of sunblocks, that are warranted and acceptable for blacks and other nonwhite populations. 4 tables, 36 references.
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Overview of Skin Cancer Detection and Prevention for the Primary Care Physician Source: Mayo Clinic Proceedings. 75:491-500, 2000. Summary: The incidence of both melanoma and nonmelanoma skin cancer is increasing, and an accurate and timely diagnosis is important to reduce the morbidity and mortality associated with these malignancies. The authors discuss clinical features and examination techniques; and the need to recognize important secondary tumor characteristics, which supplement the primary diagnosis, is reviewed. Recent evidence on etiologic factors and their importance are addressed to highlight the role of primary prevention. Pediatricians, family physicians, and all primary care physicians are encouraged to promote skin cancer awareness among children and their parents. The only tools required are clinical acumen and a thoroughly knowledgeable approach. If more medical professionals practice these strategies regularly and routinely, a reduction in this epidemic is certainly an achievable goal. Because many of the etiological factors
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are well described, physicians have an excellent opportunity to effect primary prevention through patient education. Pediatricians and family physicians also have the opportunity to commence education at the basic level. 13 figures, 1 table, 34 references. •
Sun Exposure and Skin Cancer Prevention in Children and Adolescents Source: Journal of School Nursing. 16(2):20-26, April 2000. Summary: The author investigates the topic of sun exposure and skin cancer prevention in children and adolescents, considering (1) the epidemiologic aspects of the skin cancer problem, (2) risk factors for skin cancer, (3) artificial tanning, (4) skin cancer prevention programs, and (5) the role of school nurses in preventing skin cancer in children and adolescents. As the most common form of malignancy today in the United States, nonmelanoma skin cancer (NMSC) accounts for approximately 1,200,000 cases per year, and melanoma has reached nearly 44,000 cases per year. The incidence of skin cancer has been rapidly increasing worldwide over the last 2 to 3 decades. Overexposure to sunlight has been implicated in the pathogenesis of at least 90 percent of all skin cancers. Many skin cancers are preventable, especially if preventive measures are started at an early age. NMSC's account for 90 percent of all skin cancers, and are the most common form of malignancy in whites. Malignant melanoma (MM) is less common than the two major types of NMSC, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC); but it is the most rapidly increasing form of cancer in the United States. In the absence of early detection, it is the most lethal type of skin cancer. MM is a visible malignancy with a good prognosis if diagnosed and treated early. Numerous epidemiological studies have confirmed that chronic, repeated sun exposure is the primary cause of BCC and SCC. Virtually all of these cancers are preventable. The pathogenesis of MM is more complex; but it is known to be strongly correlated with intense, intermittent exposure to ultraviolet (UV) radiation and blistering sunburns during childhood and adolescence. The risk of skin cancer also varies according to race and ethnic group. People with darkly pigmented skin have a markedly reduced skin cancer risk. They not only have some genetic protection in their skin, but are less likely than whites to seek a suntan. Fair skin type approximately doubles the risk of MM, and blond hair increases the risk by 60 percent. Genetic susceptibility, a large number of moles, and being a child of an MM patient increase the risk of acquiring skin cancer. Artificial sources of nearly pure UV-A radiation, such as tanning booths and sunbeds, represent a relatively new hazard with regard to the risk of developing any type of skin cancer. Early diagnosis is an important factor in reducing morbidity and mortality from skin cancer, but primary prevention will have the greatest impact. Most skin cancer prevention studies have targeted adults. Due to the long latent phase for premature skin aging and development of skin cancer related to UV radiation exposure, intervention programs begun during early childhood would logically be expected to be the most effective. A number of experimental skin cancer programs have been tried successfully. The Arizona Sun Awareness Project has produced two developmentally appropriate, age-related programs designed to teach children about sun safety. The preschool curriculum, Be Sun Safe, was found to have a positive effect on children's knowledge and understanding of sun safety. The elementary curriculum Sunny Days, Healthy Ways contains interactive lessons about (1) humans' relationship with the sun, (2) physical properties of the sun, (3) skin composition, (4) attitudes toward tanning and skin cancer, and (5) sun damage prevention strategies. The results of an experimental trial using this program showed success in changing knowledge, attitudes, and self-reported behavior of the children. School nurses, by virtue of their knowledge and job setting, are in a good position for educating the greatest number of children about sun exposure and skin cancer. The challenge is to translate what is known into practical, effective communications that will
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motivate students to take action to protect themselves. A number of developmentallybased, age-appropriate educational resources about sun safety have been developed to assist school nurses in this effort, including numerous online resources. 3 tables, 24 references. •
Personal and Clinical Skin Cancer Prevention Practices of U.S. Women Physicians Source: Archives of Dermatology. 136(5):633-642, May 2000. Summary: Researchers conducted a cross-sectional questionnaire survey of a representative sample of United States women physicians to document physician clinical and personal skin cancer prevention practices, and associated characteristics. They randomly selected 2,500 physicians from each of the past 4 decades' medical school graduating classes (1950 to 1989) and sent out four mailings. Participants included 3,032 nondermatologists and 95 dermatologists. Of nondermatologists, 27 percent counseled or screened their typical patients on skin cancer and sunscreen use at least once a year; 49 percent did so less frequently, and 24 percent never counseled or screened at all. Two-thirds of the dermatologists reported counseling or screening their typical patients at every visit. In bivariate analysis of nondermatologists, the distribution of counseling or screening was significantly associated with the following personal and professional characteristics: (1) Frequent sunscreen use, (2) recent skin examination, (3) good health status, (4) a primary care specialty, (5) self-confidence in counseling or screening, (6) extensive training in counseling or screening, (7) high perceived relevance to the practice of counseling or screening, and (8) nonurban practice sites and nonhospitalbased or nonmedical school-based practice. Results indicated that 48 percent of all physicians always or nearly always used sunscreen, and 25 percent had received a clinical skin examination in the previous 2 years. The researchers concluded that although many primary care physicians report ever counseling or screening their typical patients about skin cancer and sunscreen use, increased professional education for primary care physicians could improve patient counseling about skin cancer prevention. 5 tables, 58 references.
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Measure of Skin Familiarity and Its Role in the Early Detection of Skin Cancer Source: Cancer Detection and Prevention. 24(2):156-162, 2000. Summary: Australian researchers developed a measure of skin self-examination (SSE) based on familiarity or the difference between individuals' perception of the density of spots on their body and the density of spots reported by trained nurses after a visual examination of the skin. They collected data during a household survey in the Gold Coast region of Queensland, Australia. The researchers arranged 995 personal interviews with residents that were conducted by nurses. Of the respondents, (1) 48 percent were male, (2) 47.9 percent were age 50 and older, (3) 73.5 percent were married or in a relationship, and (4) 57.7 percent had at least a high school education. The interview included (1) a questionnaire that assessed skin health and personal characteristics, and (2) two skin familiarity forms. The first form was completed by the respondents without looking at their skin and the second by the nurse after a visual examination. The forms allowed the respondents and the nurse to record the density of spots on 14 body areas corresponding to high melanoma incidence. The researchers placed emphasis on four body areas: (1) Front of legs, (2) back of legs, (3) shoulders and back, and (4) feet. Results showed that (1) the internal consistency of the total body skin familiarity score (SFS) and the four body region SFS's were high, indicating good reliability; (2) the mean total-body SFS was significantly better among those who reported that they currently checked their skin, had been advised to check their skin,
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and had been taught how to check their skin; (3) women had better overall familiarity with their skin; (4) older people and those with less education were less familiar with their skin; (5) a personal and family history of skin cancer was not significantly related to total-body SFS or to SFS scores for specific body regions; and (6) sun exposure was not associated with greater familiarity with skin. The researchers concluded that (1) the SFS's correlate as expected with SSE behaviors and other personal characteristics, indicating high construct validity; and (2) skin familiarity offers some advantages over the exclusive use of SSE measures in the assessment of early skin cancer detection activities. 1 figure, 2 tables, 14 references. •
Skin Examinations and Skin Cancer Prevention Counseling by U.S. Physicians: A Long Way to Go Source: Journal of the American Academy of Dermatology. 43(2, Part 1):234-237, August 2000. Summary: Researchers reviewed new information on physician counseling for skin cancer prevention and performance of skin examinations using data collected on the 1997 National Ambulatory Medical Care Survey conducted by the National Center for Health Statistics (NCHS). Results showed that (1) skin cancer prevention counseling or education occurred in 12 million (1.5 percent) of 787 million office visits; (2) skin cancer counseling or education occurred in 1.7 percent of visits for whites, 0.43 percent for blacks, and 1.4 percent for Asian Americans/Pacific Islanders; (3) skin cancer counseling or education occurred in 1.5 percent of visits for women and 1.6 percent for men; and (4) skin cancer counseling or education occurred in 1.0 percent of visits for patients younger than age 20. Other results showed that (1) 2.8 million (35.4 percent) of 7.9 million highrisk patients received skin cancer counseling or education, (2) skin cancer counseling occurred in 30 percent of high-risk women and 39 percent of high-risk men, (3) skin examinations occurred in 62 percent of high-risk women and 61 percent of high-risk men, (4) dermatologists performed more than 100-fold more skin examinations per physician in high-risk patients than nondermatologists, and (5) significantly more patients in health maintenance organizations (HMO's) received skin cancer counseling and skin examinations than patients without HMO coverage. The researchers conclude that (1) patients are more likely to receive skin cancer counseling and skin examinations if they visit a dermatologist, and (2) dermatologists and nondermatologists should work together to continue to provide patients with preventive education. 2 tables, 12 references.
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Survey of Skin Cancer Screening in the Primary Care Setting: A Comparison With Other Cancer Screenings Source: Archives of Family Medicine. 9(10):1022-1027, November-December 2000. Summary: Researchers conducted a survey of physicians' skin cancer screening practices in primary care settings to evaluate the perceived importance and self-rated frequency of skin cancer screening compared with screening for other malignancies. They recruited 5,000 family physicians and internal medicine specialists from the Official American Board of Medical Specialists Directory of Board Certified Medical Specialists. The Directory contains professional and biographical information on board certified physicians in the United States. The physicians were mailed a questionnaire in April 1999 asking them to rate the perceived importance of screening for skin cancer using a whole body skin examination versus a digital rectal examination (DRE) in older men, a clinical breast examination (CBE) in women, and a Papanicolaou (Pap) smear test and the frequency with which they performed these examinations. Of 1,363 usable
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questionnaires returned, 814 were from family physicians and 549 were from internists. Fifty-two percent of the respondents overall rated skin cancer screening as very important, compared with 79 percent for DRE, 88 percent for CBE, and 87 percent for the Pap test. When asked about the frequency of performing the various screening tests on 81 to 100 percent of their patients, 37 percent of the physicians reported performing whole body skin examinations, compared to 78 percent who reported performing a DRE and 82 percent who reported performing a CBE. Significantly more physicians who had been in practice for more than 30 years rated skin cancer screening as extremely important and performed whole body skin examinations more frequently compared to those who had been in practice for shorter periods of time. Professional specialty and location of practice did not influence perceived importance of skin cancer screening. Physicians whose practices were in suburban settings performed skin examinations more frequently than those whose practices were in urban or rural settings. Frequency of performing skin cancer screening was not related to specialty. Overall, the selfreported frequency of skin cancer screening was strongly correlated with the physician's perceived importance of skin cancer screening. Researchers conclude that a majority of primary care physicians in this study rate skin cancer screening as extremely important. Their reported importance of skin cancer screening and frequency of skin cancer examination is significantly less than for other cancer screening examinations. This finding probably reflects a multitude of factors, including logistic constraints and lack of consensus on the efficacy of skin cancer screening. 3 tables, 38 references. •
Sun Protection is Fun! A Skin Cancer Prevention Program for Preschools Source: Journal of School Health. 70(10):395-401, December 2000. Summary: The authors describe a skin cancer prevention program developed for preschools, called Sun Protection is Fun (SPiF). The program's intervention methods are based on the Social Cognitive Theory (SCT) and emphasize (1) symbolic modeling, (2) vicarious learning, (3) enactive mastery experiences, and (4) persuasion. Based on SCT, five broad behavioral outcome objectives and six broad organizational outcome objectives were incorporated into SPiF. Examples of learning objectives for achieving the behavioral outcomes include (1) dressing children in sun protective clothing; (2) encouraging children to play in shaded areas; (3) limiting children's time spent outdoors during the hours of 11 am to 4 pm; (4) applying sunscreen with a sun protective factor (SPF) rating of at least 15 to children 30 minutes before they go outside; and (5) reapplying sunscreen to children after 1.5 to 2 hours outside, or after swimming. Examples of learning objectives for achieving the organizational outcomes of SPiF include (1) providing shade in outdoor areas used by preschoolers; (2) making sunscreen available at the preschool, on field trips, and at off-site locations, such as pools; (3) increasing the availability of suitable protective clothing; (4) changing outdoor schedules to minimize children's time outside during peak sun hours; and (5) developing and enforcing teacher policies to support the practice of sun protection. Components of SPiF include (1) a curriculum and teachers guide for promoting specific sun protective behaviors; (2) staff development sessions designed to develop teachers' skills and self-efficacy to perform the recommended protective behaviors and for conducting curriculum teaching activities; (3) videos, newsletters, and handbooks; and (4) the Sun Protective Council, one or two highly motivated individuals who lead activities to promote sun protective activities at the preschool level. SPiF is currently being evaluated in 20 Houston, Texas, preschools using a randomized controlled trial design. 5 tables, 30 references.
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Skin Cancer: New Horizons Source: RN. 63(7):32-40, July 2000. Summary: The author discusses current trends in understanding skin cancer risks and managing skin cancer. Topics include (1) the general epidemiology of and risk factors for skin cancer; (2) trends in the incidence, mortality, and prognosis for melanoma; (3) trends in the incidence, mortality, and prognosis for nonmelanoma skin cancers (basal cell (BCC) and squamous cell carcinoma (SCC)); (4) detection of skin cancer; (5) surgical treatment for BCC, SCC, and melanoma; (6) nonsurgical treatment alternatives for BCC and SCC; (7) use of additional treatments to prevent recurrences; (8) the role of patient support and education for treating skin cancer; and (9) efforts to develop a vaccine for melanoma. There has been a steady increase in the incidence of all types of skin cancer. The incidence of melanoma has been on the rise for many decades, the incidence rate increasing by a factor of 15 over the past 60 years. The depletion of the ozone layer may be a contributory factor, as it increases exposure to ultraviolet rays. Some studies link sunscreen use with higher rates of skin cancer, particularly melanoma. Surgery is the standard treatment for all skin cancers and has a high cure rate for nonmelanoma skin cancers (BCC and SCC), typically 90 to 95 percent. Nonsurgical alternatives include cryosurgery, curettage and electrodesiccation, and radiation. Newer procedures such as lymphoscintigraphy (to help determine where melanoma or SCC in some cases has spread to nearby lymph nodes) and research with vaccines and interferon may help reduce the melanoma death rate. 1 figure, 1 table, 14 references.
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Sun Protection Behaviors and Stages of Change for the Primary Prevention of Skin Cancers Among Beachgoers in Southeastern New England Source: Annals of Behavioral Medicine. 22(4):286-293, Fall 2000. Summary: Researchers investigated sun protective behaviors and readiness to adopt sun protective behaviors among beachgoers in southeastern New England as part of the Rhode Island Sun Smart Project. Trained interviewers surveyed 2,324 persons, age 16 to 65 years, by questionnaire at beaches along the Rhode Island coast during the summer of 1995. The questionnaire assessed (1) demographics, (2) attitudes toward sun protective behaviors, (3) sun protective behaviors practiced, (4) knowledge of skin cancer risk factors, (5) brief health history focusing on skin cancer factors, and (6) smoking and exercise habits. Researchers assessed sun protective behaviors using the Sun Protection Behavior Scale (SPBS). Readiness to adopt sun protective behaviors was assessed using two algorithms derived from the stages of change paradigm of the transtheoretical model. Eighty-three percent did not avoid the sun during middday and only 45 percent frequently used sunscreen. When the participants were classified according to their readiness to adopt sun protective behaviors, the largest proportion was in the precontemplation stage, for both general sun protection and for using a sunscreen with a sun protective factor (SPF) of 15 or greater (45 and 56 percent, respectively). Maintenance was the second largest stage group, including 34 percent of participants for general sun protection and 26 percent for using an SPF 15 sunscreen. The mean score of the participants on the SPBS for practicing sun protective behaviors when in the sun for 15 minutes or longer was 2.696 (range equal 1 for never using any sun protection to 5 for using all sun protection behaviors listed). For both general sun protection and using an SPF 15 sunscreen, the following variables were associated with being in an earlier stage of change: (1) Male gender, (2) younger adult, (3) lower socioeconomic status, (4) lower sun sensitivity, (5) without a family history of melanoma or personal knowledge of someone with skin cancer, (6) personal general health rated as less than excellent, and (7) being a tanning booth user. Presence of large moles, personal
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history of skin cancer, smoking status, and exercise status were not associated with stages of change for general sun protection or using an SPF 15 sunscreen. Multivariate analysis showed that the following variables were independent predictors of adopting and practicing sun protective behaviors, as measured on the SPBS: (1) Older age, (2) female gender, (3) greater sun sensitivity, (4) not using a tanning booth, and (5) knowing someone with skin cancer or melanoma. Researchers conclude that there is a need for developing interventions that target high-risk populations, such as those receiving highintensity sun exposures at beaches. 5 tables, 30 references. •
Sun Exposure and Primary Prevention of Skin Cancer for Infants and Young Children During Autumn/Winter Source: Australian and New Zealand Journal of Public Health. 24(2):178-184, April 2000. Summary: Australian researchers conducted a survey of 133 mothers living in southeast Queensland to examine the levels of sun exposure and skin protection of infants and young children. Mothers of 65 infants and 68 toddlers completed a 46-item questionnaire on children's sun exposure and mothers' levels of sun-safe behavior, particularly during autumn and winter. Researchers collected data during autumn and winter when there are high levels of ultraviolet B in Queensland. Among this sample, use of appropriate skin protection was relatively high for the mothers and their children. At age 6 months, a third of the infants had been sunburned and 15 percent had experienced painful sunburn. By age 3 years, 82 percent of toddlers had been sunburned and one-third had experienced painful sunburn, even though mothers' knowledge levels of sun-safety issues were very high. The predictors associated with primary prevention varied across the type of prevention behavior, but indicated that interventions should focus on susceptibility to sunburn and history of sunburn. Similar programs could be applicable across a broad range of sociodemographic groups, but require attention to mother's country of birth as a factor that significantly influences their use of protection for their young children. 3 tables, 30 references.
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Formative Research for Developing Targeted Skin Cancer Prevention Programs for Children in Multiethnic Hawaii Source: Health Education Research. 14(2):155-166, April 1999. Summary: Researchers conducted group discussions and interviews with children, parents, and recreation staff as a basis for the development of the SunSmart skin cancer prevention program in Hawaii. Participants included 216 children in grades 1, 2, and 3, along with 15 parents and 27 recreation staff. Ethnic backgrounds of the children were highly mixed, with about one-third being Caucasian, one-half fair-skinned Asian or mixed, and about one-fifth dark-skinned Asian, Filipino, Native Hawaiian, or mixed. Discussion groups for the children occurred in intact classrooms, using a combination of quantitative and qualitative methods. Multiple raters and an interactive process were used to analyze data from survey forms, observer impressions and audio tapes, and to draw the main conclusions. The main objectives of the SunSmart Program were to increase (1) awareness; (2) intentions; (3) skills and practices for skin cancer prevention among parents, recreation staff, and 6 to 8-year-old children; and (4) to increase environmental supports and policies to promote skin cancer prevention in outdoor recreation settings for youth. In al l groups, sun protection practices were not consistent, though general awareness about prevention was widespread. Children were reluctant to cover up with long pants, long sleeves, and wide brim hats, and did not understand what skin cance r is. Parents and recreation staff were supportive of education and policy supports, to improve both their own and the children's prevention habits. They
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were enthusiastic about interactive and creative activities. Targeted skin cancer prevention messages and strategies for Hawaii's children should promote gradual changes, provide environment supports, and involve parents and recreation staff. 3 tables, 30 references. •
Preventing Mortality in Cutaneous Melanoma Source: Patient Care. 33(9): 34-36,39-40,43-44,46,49,56-58,60. May 15, 1999. Summary: This journal article provides health professionals with information on detecting early cutaneous melanomas. It addresses screening issues, describes the features of suspicious lesions, and presents methods of treating melanoma. The main early detection tools are screening by physicians and skin self-examination by patients. Although many medical organizations do not recommend routine screening for skin cancer, the American Academy of Dermatology, the American Cancer Society, the National Institutes of Health, and the Skin Cancer Foundation do recommend skin examination or annual screening. The risk level of a particular patient is an important factor in the decision to screen for melanoma. The most effective skin examination is comprehensive, and some experts recommend dermatologic photography as a supplement to total skin examination in high-risk patients. Tools that can help diagnose a suspicious lesion include optimal illumination, side-lighting, a hand lens, and a Wood's lamp. The types of melanoma are superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, and acral-lentiginous melanoma. A biopsy is needed for all lesions meeting the ABCD (asymmetry, borders, color, diameter) criteria for melanoma. The histopathology report will indicate whether the lesion is benign or malignant. Treatment consists of surgical excision. Other treatments include chemotherapy for patients who have metastatic disease, liquid nitrogen cryosurgery, radiation therapy, and Mohs' micrographic surgery. Experimental therapies include melanoma vaccines and isolated limb perfusion. Involvement of regional lymph nodes is the most significant prognostic risk factor, followed by primary tumor thickness. The frequency of follow-up and the laboratory studies that should be obtained at each followup visit depend on the stage of disease and the risk of recurrence. Patient education is important in increasing the chances of early detection. 8 figures, 2 tables, and 11 references.
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Melanoma: A Strategy For Detection And Treatment Source: Patient Care. 30(11):126-28, 30, 34-36, 41-42, 45, 48, 53; June 1995. Summary: This journal article examines the diagnosis and treatment options of skin cancer, including the types of drugs available, identification tips, and patient counseling. The authors discuss the difficulties in identifying suspicious growths on the skin; when an autopsy is needed; monitoring when a biopsy is inconclusive; prognostic indicators in cases of positive biopsies; the clinical staging examination; and available courses of action such as surgery, adjuvant therapy, palliative therapy, and experimental treatments. Concluding comments address long-term follow-up and patient counseling. 11 references, 2 figures, 3 tables.
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Melanoma Information on the Internet: Often Incomplete: A Public Health Opportunity? Source: Journal of Clinical Oncology. 20(1):134-141, January 1, 2002. Summary: Researchers assessed the accuracy and completeness of information about melanoma that was retrievable by the use of search engines on the Internet. They
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utilized eight search engines: Yahoo, MSN, Lycos, Netscape, Go, Excite, Med Hunt, and Medical World Search. The first 30 uniform/universal resource locators (URL's) from each of the search engines using the search term melanoma were retrieved for evaluation of accuracy and completeness using a 35-point checklist rating system. The 35 items on the checklist were categorized into general information, risk factors, diagnosis, treatment, prevention, prognosis, and other factors. Searches identified 142 unique Web sites; of these, 74 could be accessed and were evaluated. Only 8 factors of 35 rating factors (24 percent) were present on at least half of the evaluated sites. The definition of melanoma occurred the most frequently, on 46 sites. Prognosis was the second most frequently included factor, mentioned on 44 sites. Factors related to prevention were present on approximately one third of the evaluated sites. Risk factors were mentioned in fewer than half the sites. Thirteen factual inaccuracies were found in 10 (14 percent) of the 74 sites. Most were relatively minor, with melanoma incidence being the most frequently stated inaccurate factor. Researchers conclude that melanoma Web sites retrieved by the search engines in this study often failed to mention much of the basic information pertaining to general aspects, risk factors, diagnosis, treatment, prevention, and prognosis. They recommend that health care providers recommend comprehensive and accurate Web sites for patients and work with their professional organizations to create complete and accurate Web sites. 6 tables, 40 references. •
Randomised Trial of Population Screening for Melanoma Source: Journal of Medical Screening. 9(1):33-37, 2002. Summary: Researchers designed a community-based, randomized trial of a population screening program for melanoma in Queensland, Australia to determine the effectiveness of such a program in reducing mortality from melanoma. The study will randomize 44 communities to receive either a community-based screening program for 3 years or standard practice. The screening program promotes both skin selfexamination and whole-body skin examination by a doctor. It includes a community education program for adults, an education program for local practitioners, and open access to skin cancer screening clinics. Strategies include (1) a guide for skin selfexamination delivered to all households, (2) posters advertising the guide in community locations, (3) brochures in doctors' offices, (4) community talks, and (5) advertisements and articles in local newspapers. In its first phase, the study was implemented in nine intervention and nine control communities. Its main outcome measure is mortality from melanoma during 15 years of followup. This first phase has highlighted the feasibility of implementing a population-based skin screening program that includes regular skin cancer screening clinics, and it has shown strong support by physicians and doctors for such a program. In the first phase after the first 12 months of the trial, there has been a significant 2.5-fold increase in participation in screening within intervention communities, with no similar increase within the control communities. The researchers conclude that the design of this community-based, randomized trial of melanoma screening has been successfully peer reviewed and has proven feasible in practice. 1 figure, 1 table, 32 references.
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Epidemic of Malignant Melanoma: True Increase or Better Detection? Source: Journal of the American Medical Association. 287(17):2201, May 1, 2002. Summary: The author discusses the apparent rise in incidence of malignant melanoma (MM) in the United States, based on a debate at the annual meeting of the American Academy of Dermatology. While the lifetime risk of developing invasive MM in the United States was 1 in 1,500 in 1930, today it is 1 in 68. Some experts say this rise in
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incidence reflects a true increase in the disease, while others contend it is an artifact of more intensive recent surveillance. Research indicates that the frequency of MM is continuing to rise in the United states among all age groups, particularly people over age 59 years. Research also indicates a rise in MM incidence worldwide. The incidence of thin invasive lesions is increasing faster than that of thick ones, which reflects earlier detection by physicians and greater public awareness of warning signs of skin cancer. There have been no significant changes in histological criteria for the diagnosis of MM in recent years. About 82 percent of MM's are diagnosed at a localized stage. Some experts suggest that the rise in MM incidence may in part reflect longer life expectancy as well as efforts to detect MM earlier. Minimizing sun exposure, especially midday, and wearing protective clothing and sunscreen can lower the risk of MM and other skin cancers. As part of a public education effort, the American Association of Dermatologists conducts an annual National Sports Skin Cancer Awareness Program and provides free screenings to all major league baseball players, coaches, family members, and office staff. •
Use of Topical Sunscreens and the Risk of Malignant Melanoma: A Meta-analysis of 9067 Patients From 11 Case-control Studies Source: American Journal of Public Health. 92(7):1173-1177, July 2002. Summary: Researchers performed a meta-analysis of studies examining the association between sunscreen use and malignant melanoma risk. They conducted a literature search to identify published case-control or cohort studies on adults that provided data on the frequency of sunscreen use and the proportion of participants diagnosed with melanoma. After exclusions, 11 studies remained for analysis. The 11 studies produced OR's for the frequency of sunscreen use being associated with melanoma of 0.2 to 3.34. Four of the studies used nonheterogeneous data from population-based registries. These yielded a summary RR of 1.01 (95 percent confidence interval (CI) 0.46 to 2.28), a statistically insignificant result, indicating no association between sunscreen use and increased melanoma risk. The remaining seven studies used hospital databases. They produced a summary RR of 2.41 (CI 0.32 to 18.1). The Q statistic indicated that their data were highly heterogeneous. The apparent positive association (RR of 2.41) was attributed to biases associated with using hospital-based data. Researchers conclude that currently available epidemiologic data do not support the existence of a relationship between topical sunscreen use and an increased risk of malignant melanoma. 3 tables, 21 references.
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Ultraviolet A and Melanoma: A Review Source: Journal of the American Academy of Dermatology. 44(5):837-846, May 2001. Summary: The authors reviewed and discussed the issue of whether ultraviolet-A (UVA) radiation is a causative factor for human melanoma. The review (1) summarizes the characteristics of UVA and ultraviolet-B (UVB) radiation and their biological effects, (2) discuses scientific evidence that UVA radiation is a risk factor for melanoma, (3) discusses epidemiologic studies investigating UVA radiation and melanoma, and (4) discusses clinical evidence for UVA radiation being a risk factor for melanoma. The incidence and mortality rates of melanoma have increased during the past several decades in the United States. Among the reasons for these trends, increased exposure to UV radiation as a result of lifestyle changes, is generally recognized as an important factor. Sunburns have been identified as a risk factor for the development of melanoma. Because sunburns are primarily due to UVB radiation, which leads to chromosome damage, UVB is strongly absorbed by DNA, UVB radiation has been implicated as a
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major causative factor for melanoma. The role of UVA radiation as a possible etiologic factor for melanoma has received less attention, even though excessive sun exposure is also associated with excessive UVA exposure. UVA causes DNA damage through photosensitized reactions that lead to the production of reactive oxygen species. UVA has been shown to produce mutations in a variety of cultured cell lines. UVA radiation has been reported to produce melanomas and melanoma precursors in a hybrid fish and in the opossum. UVA radiation has also been reported to induce immunosuppression in laboratory animals and humans. Some, but not all, epidemiologic studies have reported an increase in melanoma incidence in users of sunbeds and sunscreens, and in patients undergoing psoralen and UVA therapy for psoriasis. The authors conclude that basic scientific evidence of the harmful effects of UVA radiation on DNA, cells, and animals exist. Collectively, these data suggest a potential role for UVA in the pathogenesis of melanoma. Evidence from epidemiologic and clinical studies is inconclusive but appears to be consistent with this view. 106 references. •
Current Practice and Future Trends in Malignant Melanoma Source: Journal of the Louisiana State Medical Society. 153(4):191-197, April 2001. Summary: The author discusses current practices and future trends in diagnosing and treating malignant melanoma. The article (1) discusses risk factors for melanoma; (2) reviews standard approaches to preventing, diagnosing, staging, and treating melanoma; and (3) discusses new trends in melanoma care. A number of melanoma risk factors have been identified, including (1) red or blond hair; (2) family history of melanoma; (3) actinic keratoses; (4) pronounced freckling on upper back; (5) three or more blistering sunburns before age 20 years; and (6) 3 years or more of outdoor summer jobs during the teen years. The presence of one of the six risk factors confers a three-fold risk on a patient. If three or more risk factors are present, the risk increases 20fold. The amount of sun exposure and sunburning are the only risk factors that can be modified. Melanomas have been traditionally staged using the American Joint Committee on Cancer system which considers (1) tumor stage, (2) regional lymph node analysis, (3) presence or absence of distant metastases, and (4) stage grouping. Excisional biopsy and chemotherapy have been standard treatments. New concepts in melanoma care include (1) sentinel lymph mapping, (2) immunotherapy, and (3) melanoma vaccines. The use of vaccines is considered one of the more exciting areas of melanoma research. Different types of vaccines have been tested, using autologous and allogenic whole melanoma cells or melanoma specific antigens such as peptides or gangliosides. Ganglioside GM2 is an example of a melanoma specific antigen used in vaccine therapy. Melanoma patients with natural antibodies to GM2 have been shown to have prolonged survival compared with those without the antibodies. Patients in whom GM2 antibodies can be stimulated also show improved survival. The article summarizes information on how melanoma patients in Louisiana can obtain information on clinical trials immunotherapy and chemoimmunotherapy. 1 table, 44 references.
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Melanoma Update: 2001 Source: Skin Cancer Foundation Journal. 19:13-14, 2001. Summary: The author discusses what is known about the risk of melanoma today. The rate of malignant melanoma in the United States is rising faster than that of any other cancer. Over the past decade, the risk has more than doubled, and over the past halfcentury, it has increased more than 20-fold. The risk is projected to rise to 1 in 50 by the year 2010. Although malignant melanoma accounts for only 5 percent of all skin cancers,
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it causes more than three-quarters of skin cancer deaths. It is the most frequent cancer in United States women age 25 to 29 years and the second most frequent for women age 30 to 34 years. There are multiple factors that influence the risk of developing melanoma, including (1) fair hair, light eyes, and light complexion; (2) family history of malignant melanoma; (3) actinic keratosis; (4) marked freckling of the upper back; (5) three or more blistering sunburns before age 20 years; and (6) outdoor jobs for 3 or more years during adolescence. Having one or two of the risk factors increases a person's risk three to four times, and having three or more increases the risk almost 20-fold. Though malignant melanoma can be lethal, it is not uniformly fatal. The United States survival rate increased to 85 percent in the late 1980's. The factor that best predicts survival is thickness of the primary lesion. Thus, early detection by identification of suspicious lesions is essential. The best way to remember early warning signs is to remember the ABCD rule (Asymmetry, Border, Color, Diameter). Other factors that can predict outcome include clinical stage, anatomical site, and ulceration. Sun protection and early detection currently are the first line of defense against malignant melanoma. 9 references. •
Assessment of Knowledge of Melanoma Risk Factors, Prevention, and Detection Principles in Texas Teenagers Source: Journal of Surgical Research. 97(2):179-183, May 15, 2001. Summary: Researchers assessed the knowledge of melanoma risk factors, prevention, and detection principles among Texas teenagers. They administered a questionnaire consisting of 31 true/false questions to 220 students, age 12 to 19 years, at public junior and high schools in Dallas and Houston, Texas, from November 1999 through February 2000. The questions evaluated a broad range of knowledge about sun exposure and melanoma. After the students completed and returned the questionnaire during a required health education class, the teachers provided the correct answers and detailed explanations of each test item to the students. After a 30-minute period for review of the answers and explanations, a questionnaire was administered to measure the influence the learning exercise may have on students' future sun protection and melanoma prevention behaviors. Researchers divided the students into two age groups (12 to 15 years and 16 years or older) for comparing the questionnaire responses and the scores on the knowledge examination. Seventy-one percent of all students reported sunbathing outdoors and 18 percent reported using a tanning bed in the past 6 months. Thirty-three percent reported experiencing at least three blistering sunburns in the past. The average score on the knowledge test was 60 percent for students 16 years or older and 54 percent for those age 12 to 15 years. Students in the younger age group were significantly more likely to indicate that they planned to change their future behavior with respect to performing skin self-examinations and limiting sun exposure compared to the older students. Researchers conclude that a significant number of teenagers have already increased their risk for future melanoma by suffering severe sunburns. Students younger than 16 were significantly more likely to report that they intended to change their future behaviors after receiving information about melanoma. The results of this study support a need for educational interventions targeting younger age groups to most effectively reduce the risk of developing future melanoma. 9 figures, 16 references.
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Ultraviolet Light as a Topical Agent for Malignant Melanoma and the Role of Sunscreen (Editorial) Source: Pediatric Annals. 30(4):185-186, 202, April 2001.
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Summary: The author presents a pediatrician's view of the role of ultraviolet (UV) radiation and sunscreen use in the etiology of malignant melanoma. The editorial addresses (1) why melanoma is important in pediatrics, (2) UV radiation as modifiable risk factor for melanoma, (3) whether sunscreens can help protect against melanoma, and (4) best practices for melanoma protection. Melanoma causes three times as many deaths as the two nonmelanocytic skin cancers, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Mortality rates from BCC and SCC are decreasing, whereas deaths from melanoma are increasing. Melanoma incidence can be correlated with episodic (intermittent) sun exposure starting in childhood as opposed to SCC which is correlated with lifelong chronic sun exposure. Sunscreen does not appear to be effective against melanoma because sunscreen use has been associated with more childhood sunburns, a risk factor for melanoma. This is attributed to people using sunscreen to enable them to spend more time in the sun, thereby increasing the risk of sun damage. Best practices for melanoma protection involve teaching parents to focus on preventing sunburns in their children. Parents should understand that although sunscreens are important, over reliance on sunscreens can increase the risk of melanoma. Parents should individualize sun protective interventions based on their child's skin color and susceptibility to burns, family history (including diseases that predispose to melanoma), and the presence of moles. Sunscreen should not be used as an excuse to stay in the sun longer. 12 references. •
Pilot Study Using Nurse Education as an Intervention to Increase Skin Selfexamination for Melanoma Source: Journal of Cancer Education. 15(1):38-40, Spring 2000. Summary: Researchers conducted a pilot study to determine factors important to the design of a nurse education intervention to increase the frequency of skin selfexamination (SSE) practices. A group of 99 people age 14 to 81 were enrolled between April 1988 and February 1989. The subjects were (1) high-risk individuals with a history of melanoma or multiple atypical nevi attending the Yale University Pigmented Lesion Clinic; and (2) low-risk individuals without melanoma who participated in an ongoing, population-based, case-control study of melanoma. A dermatologist completed a complete skin examination and nevus count, removing melanocytic lesions suggestive of early melanoma. The total number of pigmented lesions previously biopsied was determined by chart review and questionnaire. Two or more melanocytic lesions were chosen for close-up photography. Researchers took whole-body photographs of each person. After this initial exam, each person completed a baseline survey about the frequency of SSE, the perceived risk of developing melanoma, and knowledge of the clinical signs and risk factors for melanoma. Following this, each person completed an educational session with a dermatology-trained registered nurse. The nurse reviewed the clinical characteristics of cutaneous melanoma, risk factors for melanoma, and methods for conducting SSE. Each person received educational materials on the subject and a diary for recording the frequency of SSE and areas of the body examined. Assessment occurred at each person's next regular clinic visit 6 to 18 months later. The evaluation included a posttest to assess change in knowledge about melanoma and ascertain frequency and thoroughness of SSE. Diaries were collected, and participants evaluated the intervention. Data analysis indicated that of the 75 people who completed all parts of the study, (1) 37 had personal histories of histologically-verified cutaneous melanoma, (2) 23 had histories of histologically- or clinically-verified atypical nevi, and (3) 15 had neither. The results indicated that this intervention had the potential to modify SSE behavior toward an optimal goal of SSE once every 1 to 2 months. The
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intervention led to a doubling of practice of SSE. Increases in optimal SSE were associated with increases in knowledge about melanoma. 3 tables, 15 references. •
New American Joint Committee on Cancer Staging System for Cutaneous Melanoma Source: Cancer. 88(6):1484-1491, March 15, 2000. Summary: The Melanoma Staging Committee and the American Joint Committee on Cancer (AJCC) has proposed major revisions of the melanoma TNM and stage grouping criteria. The committee members represent most of the major cooperative groups and cancer centers worldwide with a special interest in melanoma. The committee also collectively has had clinical experience with over 40,000 patients. The new staging system better reflects independent prognostic factors that are used in clinical trials and in reporting the outcomes of various melanoma treatment modalities. Major revisions include (1) melanoma thickness and ulceration, but not level of invasion, to be used in the T classification; (2) the number of metastatic lymph nodes, rather than their gross dimensions, the delineation of microscopic versus macroscopic lymph node metastases, and presence of ulceration of the primary melanoma to be used in the N classification; (3) the site of distant metastases and the presence of elevated serum lactate dehydrogenase, to be used in the M classification; (4) an upstaging of all patients with Stage I, II, and III disease when a primary melanoma is ulcerated; (5) a merging of satellite metastases around a primary melanoma and in transit metastases into a single staging entity that is grouped into Stage III disease; and (6) a new convention for defining clinical and pathologic staging so as to take into account the new staging information gained from intraoperative lymphatic mapping and sentinel lymph node biopsy. The AJCC Melanoma Staging Committee invites comments and suggestions regarding this proposed staging system before a final recommendation is made. 2 tables, 56 references.
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Early Detection of Melanoma Reduces Health-care Costs Source: Primary Care and Cancer. 20(5):23-25, May 2000. Summary: A researcher estimated the direct health care costs associated with the diagnosis and treatment of cutaneous melanoma, and the impact of indirect costs. In 2000, there will be an estimated 47,700 new cases of melanoma in the United States, and 7,700 deaths will occur. To estimate the direct annual cost of melanoma, its diagnosis, treatment, surveillance, and associated deaths, a model was created based on patients at the Massachusetts General Hospital Melanoma Center and the Boston University School of Medicine. From this study, it was calculated that the annual direct costs, i.e., costs limited to actual treatment of the cancer, were $562 million. Taking the aggregate of indirect costs as amounting to at least twice the direct cost, the actual financial impact per year may be in the range of $1.5 billion. More than 90 percent of the total direct cost of treating melanoma was attributable to fewer than 20 percent of the patients. The vast majority of patients had their cancer limited to the skin, and as a group consumed only about 10 percent of health care resources. Only 4.7 percent of the direct health-care costs for melanoma are spent on diagnosis. If screening efforts were doubled, the number of new patients diagnosed with metastatic disease could be reduced from 12 to 6 percent. This would result in significant economic savings. 3 figures, 5 references.
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Malignant Melanoma: Prevention, Early Detection, and Treatment in the 21st Century Source: CA: A Cancer Journal for Clinicians. 50(4):215-236, July-August 2000.
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Summary: Physicians review the literature on the prevention, early detection, and treatment of malignant melanoma. Prevention and early detection remain the primary goals in the war against this cancer. With improved professional education, public awareness, patient education, and research advances, it may be possible to decrease the incidence and mortality of this disease. However, as melanoma incidence continues to rise, the best weapon will be a multidisciplinary approach using the best skills available. This review (1) provides information to assist in the identification of individuals at high risk for melanoma; (2) notes the means to recognize potentially early melanomas using the guidelines of asymmetry, border irregularity, color variegation, and diameter; (3) discusses how to advise patients regarding skin self-examination and sun protection measures; and (4) considers the selection of appropriate treatment for melanoma, depending on the clinical stage. 10 figures, 2 tables, 123 references. •
Is Routine Screening for Melanoma a Benign Practice? Source: Journal of the American Medical Association (JAMA). 284(7):883-886, August 16, 2000. Summary: Physicians consider recommendations concerning routine screening for melanoma, and the consequences of routine screening. The incidence of malignant melanoma is increasing rapidly in many countries in the world. An estimated 4 percent increase per year has been observed in the United States in the last 20 years. Recommendations by various organizations have addressed the issue of routine screening for skin cancer. Questions have been raised about the degree to which the increase in melanoma may or may not be real. Virtually all of the increase in melanoma incidence is accounted for by an increase in thin tumors. The implication is that there is an overdiagnosis of melanoma in screened populations whereby patients with benign nevi or indeterminate lesions are being falsely diagnosed with melanoma. Problems with the diagnoses of early melanoma are discussed, along with controversies in the diagnosis of atypical/dysplastic nevi. The authors suggest several alternatives to population-based screening, including the emphasis by primary care practitioners on the use of appropriate preventive measures. Light-skinned individuals need to be educated about the importance of limiting sun exposure and avoiding sunburns, particularly for children and teenagers. Primary care clinicians should be able to identify patients with atypical mole and melanoma syndrome who are at particularly high risk for melanoma. In contrast to the role of primary care physicians, there is reason to believe that routine screening of high-risk patients by dermatologists may be beneficial. The current challenge for the dermatologic community is that criteria for the diagnosis of melanoma and melanocytic nevi must be refined and more accurately applied. 23 references.
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Early Detection of Melanoma Source: Journal of the American Medical Association (JAMA). 284(7):886-889, August 16, 2000. Summary: A physician discusses the roles of the dermatologist, patients and their families, and the primary care clinicians in the early detection of melanoma. Most melanomas that have not already metastasized are visible on the skin surface to the naked eye. Early detection requires inspection of the skin. For high-risk patients, dermatologists are providing cutaneous examinations and are making increasing use of tools, such as photography and in vivo epiluminescence microscopy. Thorough skin self-examination is key to early detection of melanoma by patients and their families. Early detection by primary care clinicians faces significant barriers, including limited
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skills in the recognition of melanoma, lack of confidence in their ability to diagnose melanoma, and time constraints. In Queensland, Australia, which has the highest recorded incidence of melanoma of any large population, an effort is under way to conduct an evaluation of multicomponent community-based early detection efforts that include thorough skin self-examination, whole body examination by primary care clinicians, and specialized screening clinics. Assuming this evaluation proceeds according to plan, results for the mortality end point from this investigation are expected to be complete in the year 2015. 50 references. •
Time Trends of Cutaneous Melanoma in Queensland, Australia and Central Europe Source: Cancer. 89(6):1269-1278, September 15, 2000. Summary: Researchers assessed recent developments in clinical and pathological features of invasive melanoma in Queensland, Australia, and in Germany, Austria, and Switzerland, from 1986 to 1996. The researchers analyzed data from registries or dermatology departments from these countries. Results showed that (1) the percentage of patients in Germany diagnosed with a primary tumor increased from 91.4 percent in 1986 to 96.2 percent in 1996, (2) this increase corresponded to a decrease in patients with satellite or in-transit metastases from 4.5 percent in 1986 to 1.2 percent in 1996, (3) the percentage of male patients with melanoma increased significantly in both Australia and Central Europe, (4) the mean age at diagnosis increased significantly from 52 to 55 years in both Australia and Central Europe, and (5) the most prominent anatomic areas for melanoma were the trunk for men and the lower extremities for women. Other results showed that (1) in Australia, Breslow tumor thickness varied between 0.5 and 0.6 millimeters (mm) with no significant linear trend over the study time period; (2) in Central Europe, Breslow tumor thickness decreased significantly from 1.2 mm in 1986 to 0.8 mm in 1996; (3) in Central Europe, the percentage of thin melanomas increased from 29.8 percent in 1986 to 46.4 percent in 1996; (4) the percentage of patients with Clark Level II invasion increased significantly in both Australia and Central Europe; (5) the percentage of superficial spreading melanomas increased significantly in Central Europe, but decreased significantly in Australia; and (6) in both Australia and central Europe, younger people and women were more likely to have thinner melanomas. The researchers conclude that (1) in both Australia and Central Europe, the trend was toward thinner and less invasive melanomas from 1986 to 1996; and (2) men and elderly persons should be the focus of skin cancer prevention activities. 5 figures, 2 tables, 45 references.
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Demographic Predictors of Melanoma Stage at Diagnosis Source: Archives of Family Medicine. 9(7):606-611, July 2000. Summary: Researchers examined whether sociodemographic characteristics are predictive of late-stage melanoma diagnosis. They (1) identified 1,884 incident cases of melanoma occurring in Florida from January 1994 to January 1995 whose stage at diagnosis was available, (2) linked cases with state inpatient and outpatient discharge abstracts, and (3) matched cases with 1990 United States Census data to get censusderived measures of sociodemographic status. They assessed seven variables as possible predictors of late-stage melanoma diagnosis: (1) Age, (2) sex, (3) marital status, (4) smoking status, (5) education level, (6) household income, and (7) urban versus rural residence. Results showed that (1) mean patient age was 62.4 years with a range of 13 to 99 years; (2) most patients were male; (3) 243 patients (12.9 percent) were diagnosed as having melanoma that had spread to lymph nodes or distant sites; (4) late-stage diagnosis was more common among patients who were male, unmarried, smokers, and
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who lived in communities with low median incomes and education levels; and (5) age was not a predictor of late-stage melanoma diagnosis. The researchers conclude that physicians should (1) be aware that factors other than family history and sun exposure may increase the likelihood of late-stage melanoma, and (2) screen at-risk patients more conscientiously. 3 tables, 41 references. •
Is the Incidence of Malignant Melanoma Decreasing in Young Australians? Source: Journal of the American Academy of Dermatology. 42(4):672-674, April 2000. Summary: Researchers discuss reported decreases in the incidence of malignant melanoma in young Australians. Recent studies have suggested that the incidence of malignant melanoma has been decreasing in young Australian women since the mid1980's, but the changes in the racial composition of the Australian population was not accounted for in these studies. Since 1971, there has been an increase in the percentage of the Australian population of people born in Asia, the Middle East, and the Pacific Islands. For this analysis, the researchers divide the Australian population into high-risk people (HRP) and low-risk people (LRP). HRP are those born in Australia, with the exception of Aborigines and Torres Strait Islanders (ATSI's), and those born in Europe and North America. LRP include ATSI's, and those born in Asia, the Pacific Islands, and the Middle East. Results based on census data showed that (1) the overall percentage of HRP fell from 97.8 percent in 1933 to 88.9 percent in 1996; (2) the largest decrease was between 1981 and 1996; (3) over the same period, the overall percentage of LRP increased from 1.3 percent to 8.8 percent; (4) these figures do not include Australianborn children of LRP; and (5) immigrants to Australia are relatively young, Asian, and female, and 46 percent settle in New South Wales. The researchers conclude that (1) there has been a large increase in the percentage of the Australian population that is at very low risk for malignant melanoma, (2) the effect of immigration helps explain the reversal of the latitude gradient of malignant melanoma that has been reported from Australia, and (3) epidemiologists from Australia must analyze the composition of their study populations annually to account for the effect of immigration and the changing racial composition of the Australian-born population on skin cancer statistics. 5 tables, 16 references.
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Prevention and Early Diagnosis of Cutaneous Melanoma Source: New Jersey Medicine. 37-39, May 2000. Summary: A physician discusses the prevention and early diagnosis of melanoma. The rate of melanoma increased 4 to 6 percent annually during the early 1990's, then increased 12 percent in 1996. Today, about one American dies of melanoma every hour, and 41,600 United States patients are expected to be diagnosed with melanoma this year, resulting in 7,000 to 9,000 deaths. Genetic factors and sun exposure are the most important determinants of melanoma risk. Exposure to ultraviolet B (UVB) and, to a lesser extent, ultraviolet A (UVA) radiation has been linked to skin cancer, immune suppression, cataracts, and other health problems. Melanoma risk appears to be related to severe episodic UVB exposure resulting in sunburns. No evidence exists that tanning protects against the development of melanoma. Tanning beds usually use UVA radiation to induce tans, but there is some evidence that tans induced by UVA are less protective against the development of sunburn. Sunscreens have been used to prevent sunburning, but there is no conclusive evidence that sunscreens protect against the development of basal cell carcinoma or melanoma. There is no evidence that sunscreen use increases the risk of melanoma. Therefore, people should continue to use sunscreens with a sun protection factor of at least 15 and minimize sun exposure by avoiding peak
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hours and wearing sunglasses and wide-brimmed hats. Public and professional education campaigns are under way that aim to decrease the incidence of chronic sun exposure in children and adolescents. Programs to decrease the depletion of the ozone layer are also under way. The best chance for a cure for melanoma is early detection and proper surgical care. Self-examination and skin screening during routine physical examinations are more effective in detecting skin cancer than mass screening. The author concludes that public education, physician education, mass screenings, and individual screening should lead to a decrease in the incidence of melanoma. 14 references. •
Increasing Supplies of Dermatologists and Family Physicians Are Associated With Earlier Stage of Melanoma Detection Source: Journal of the American Academy of Dermatology. 43(2, Part 1):211-218, August 2000. Summary: Researchers examined whether primary care physician supply and the supply of dermatologists were related to stage at diagnosis for malignant melanoma. They (1) identified all 1,884 incident cases of melanoma in Florida in 1994 for which stage at diagnosis was available using Florida's statewide cancer registry, (2) supplemented registry information with data from the 1990 United States Census, and (3) collected data on physician supply from the 1994 American Medical Association Physician Masterfile. Results showed that (1) most patients were white, male, and married with a mean age of 62.1 years at diagnosis and a relatively high socioeconomic status; (2) some patients lived in areas with no physicians while others lived in areas with 1 physician for every 20 residents; (3) there was similar variation in the supply of dermatologists and primary care physicians; (4) most patients lived in areas without a practicing dermatologist; and (5) there was no association between total physician supply at the geographical area level and the odds of early-stage diagnosis. Other results showed that (1) each additional dermatologist per 10,000 persons was associated with 39 percent increased odds of early diagnosis; (2) each additional family physicians per 10,000 persons was associated with 21 percent increased odds of early diagnosis; (3) each additional general internist per 10,000 persons was associated with 10 percent decreased odds of early diagnosis; (4) for patients with fee-for-service insurance, earlier stage at diagnosis was associated with greater supplies of dermatologist and family physicians; and (5) there were no significant relationships between physician supply and stage at diagnosis among patients having health maintenance organization insurance types. The researchers conclude that (1) increasing supplies of dermatologists and family physicians were associated with greater likelihood of early melanoma detection, (2) increasing supplies of general internists were associated with reduced odds of early melanoma detection, and (3) the composition of the physician workforce may affect important health outcomes and is worthy of further study. 6 tables, 55 references.
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Sunscreens, Nevi, and Melanoma Revisited (Editorial) Source: Archives of Dermatology. 136(12):1549-1550, December 2000. Summary: The author comments on a prospective, randomized controlled trial to determine whether the use of a broad-spectrum sunscreen with a sun protection factor (SPF) of 30 reduces the development of melanocytic nevi in white Canadian children. In the study, Gallagher and colleagues randomized 458 children in first through fourth grades in 1993. The researchers instructed the parents of the 222 children assigned to the treatment group to apply sunscreen to exposed skin when the child was expected to be
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in the sun for 30 minutes or longer. The parents of the 236 control children received no sunscreen advice. The researchers counted the children's nevi at baseline and at a 3-year followup. Only 309 children remained for analysis at followup. Results showed that (1) children in the sunscreen group developed fewer nevi than children in the control group; (2) after controlling for grade in school, sex, and hair color, heavily freckled children in the sunscreen group developed fewer nevi than heavily freckled children in the control group; and (3) children with no freckling had little advantage when randomized to the sunscreen group compared with the control group. The researchers concluded that broad-spectrum sunscreens may reduce the number of nevi in white children, especially if they have freckles. The editors note that the strengths of this study are that (1) it was prospective, (2) there was concealed randomization of children, (3) it was observer-masked, (4) there was objective assessment of outcome, and (5) there was careful adjustment for confounding factors in the data analysis. The weaknesses of this study are (1) the lack of subject masking, (2) unequal treatment of groups, and (3) the inclusion of only patients who completed the study in the analysis. The editors note that these results and the results of previous case-control studies raise the question of what to do when there is conflicting evidence. The editors conclude that the best available evidence suggests that practicing dermatologists should counsel their patients to reduce their sun exposure and to use a broad-spectrum sunscreen with a high SPF. 4 references. •
Is the Self-counting of Moles a Valid Method of Assessing Melanoma Risk? (Editorial) Source: Archives of Dermatology. 136(12):1550-1551, December 2000. Summary: The editors comment on a case-control study by Buettner and colleague to assess whether people can identify themselves as being at risk for melanoma through the self-counting of moles. In this study, the patient population consisted of 513 patients with melanoma diagnosed in 1991 who were recruited from nine university dermatology departments in Germany, Austria, and Switzerland; and 498 patients without melanoma as controls. They educated the treatment participants on the selfassessment of benign moles. The researchers asked the participants and dermatologists to categorize the total number of moles on the whole body and on both arms. Results showed that (1) the treatment participants significantly underestimated the number of moles, (2) overall agreement was poor, and (3) the ability to detect existing moles was low. The researchers concluded that (1) the self-assessment of moles on the whole body was hard to perform accurately; (2) people tended to undercount them; and (3) counting moles should be the responsibility of dermatologists, but people should be educated in the performance of skin self-examination as a key component in the early detection and prevention of melanoma. The editors note the difference between the title of the casecontrol study, which focused on agreement of mole counts between patients and dermatologists, and the stated aim of the study, which was to assess whether self-counts can identify melanoma risk. For measuring agreement, the statistics suggested the counts by patients do not agree with counts by dermatologists. For measuring risk assessment, the correlation between patient and dermatologist counts was good. The editors conclude that (1) this study did not suggest that failure to accurately self-assess mole counts translates into ineffective skin self-examination practices, and (2) the motivation to perform skin self-examination may be improved if patients are identified as being at high risk for melanoma. 9 references.
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Rising Incidence of Melanoma in Children and Adolescents Source: Dermatology Nursing. 12(3):188-189, 192-193, June 2000.
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Summary: Physicians discuss (1) the incidence of melanoma in children, (2) sun exposure and other risk factors for melanoma, and (3) the prognosis of melanoma in children and adolescents. The few studies that have been conducted have indicated that the incidence of childhood and adolescent melanoma is increasing. This increasing trend is attributed to increasing amounts of intense sun exposure during childhood and adolescence. Other risk factors for melanoma include (1) congenital melanocytic nevi and dysplastic nevi, (2) being fair skinned and having blond or red hair, and (3) having a tendency to freckle. The prognosis for children and adolescents with melanoma is similar to that of adults when cytologic features, gender, location, and race are taken into account. Prognosis is determined by two crucial factors: (1) Tumor thickness and (2) the presence or absence of lymph node involvement. Because the primary treatment for melanoma is surgical excision, early detection and removal of these lesions results in less morbidity for the patients as well as a better chance for a cure. Since the incidence of melanoma in children and adolescents is low, health care providers tend to overlook melanomas and when they do notice pigmented lesions during a physical examination, few providers suspect this diagnosis. Health care providers, therefore, must be vigilant for the occurrence of melanoma and should consider an early skin biopsy to assist in its diagnosis. Providing early sun protection is important for preventing melanoma. Children should be protected from intermittent, intense sun exposure, particularly those who are fair skinned and have blond or red hair. An effective regimen of sun protection includes (1) avoiding sun exposure during the midday and early afternoon hours, (2) wearing protective clothing; and (3) applying a high SPF broad-spectrum sunscreen. 26 references. •
Plan to Promote the Prevention and Early Detection of Melanoma Source: Dermatology Nursing. 12(5):329-333, October 2000. Summary: A nurse describes a program to promote the prevention and early detection of melanoma. The program was developed for schools, pediatricians, nurses, and state agencies in Anne Arundel County, Maryland, and has the following goals and objectives: (1) Teach nurses and the general public that melanoma is a serious preventable public health problem, (2) promote preventable behaviors among the public, (3) advocate early detection of melanoma through education, (4) ultimately decrease the incidence of melanoma and other skin cancers, (5) increase the awareness of nurses regarding their ability to educate the public and change behaviors regarding melanoma and other public health problems, and (6) target those who are at high risk. To meet the first objective, nurses who do not work in dermatology must be educated about melanoma. All of the 85 school health nurses working in the Anne Arundel County public school system will be invited to attend an educational program about melanoma. Nurses working with the approximately 80 pediatricians in Anne Arundel County will also be invited to attend the educational program. Other specific targets for the program include (1) school children, (2) boat owners, (3) travel agencies, and (4) cars crossing the Chesapeake Bay Bridge. To promote skin cancer education among school children, the Sunnysaurus coloring book that teaches children about sun safety will be given to each child just before summer break. Sunscreen samples that will carry labels with sun protective messages will be made available to boat owners. Drivers of cars crossing Chesapeake Bay Bridge who live in Anne Arundel County will be offered literature about melanoma and its prevention. Travel agents will be given sunscreen samples to distribute to vacationers before their trip. 2 figures, 18 references.
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Early Detection and Treatment of Melanoma: Update 2000 Source: Dermatology Nursing. 12(6):397-402, 441, December 2000. Summary: The author presents and discusses recommendations for the early detection and treatment of melanoma, updated for 2000. The recommendations cover the following topics: (1) Risk factors for melanoma; (2) recommended biopsy techniques, including histopathology and staging; and (3) treatment recommendations. Identifying people with risk factors, educating them to perform skin self-examinations, and to seek early medical care if a suspicious lesion is seen can enhance the early detection of melanoma. Early detection and diagnosis are considered critical for obtaining a surgical cure because of the aggressive nature of melanoma and its poor response to treatment after distant metastases develop. This means that survival ultimately depends on the stage of disease at the time of diagnosis. The discussion of treatments describes the Sunbelt Melanoma Clinical Trial, an ongoing clinical trial that seeks to answer the question of whether early detection of occult lymph node disease by sentinel nodal biopsy with immunohistochemical staining polymerase chain reaction makes a difference in survival when coupled with lymph node dissection and adjuvant therapy with interferon. 3 figures, 7 tables, 22 references.
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Signs and Symptoms of Melanoma in Older Populations Source: Journal of Clinical Epidemiology. 53(10):1044-1053, October 2000. Summary: To assess the relationship between increasing age and the reporting of signs and symptoms of melanoma, researchers conducted a descriptive study in two populations of melanoma cases, one with 634 hospital-based and one 624 populationbased incident cases. They used multivariate logistic regression to evaluate the relationship between being over age 50 years and the reporting of melanoma signs and symptoms. Older patients were less likely to report itching and changes in elevation of their lesions. Change in color was also less likely to be reported by older patients, although this was not statistically significant. Ulceration of the lesion was reported significantly more often by older patients. Researchers conclude that older individuals may be less likely to report itching and change in elevation or color of their lesions, but more likely to report ulceration, a symptom which is associated with advanced disease and poor prognosis. Further study is needed to provide a better understanding of the development of melanoma in older populations so that new strategies can be explored to improve early detection in this age group. 2 figures, 5 tables, 36 references.
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Malignant Melanoma in the Year 2000 (Editorial) Source: CA: A Cancer Journal for Clinicians. 50(4):209-213, July-August 2000. Summary: The author discusses the current state of knowledge about melanoma, based on the Australian experience. Although 65 percent of melanomas occurring in white populations worldwide are attributable to sun exposure, the precise role of sun exposure in the causation of melanoma is still unclear. For example, outdoor workers generally have a lower risk of melanoma as compared to indoor workers. Blistering sunburn in childhood and adolescence is an almost universal risk factor for melanoma in white populations. In Australia, the use of sunscreens is understood as a default option. The public health message is that sunscreens are only to be used when other measures do not provide sufficient protection. The notion that one should not rely on a sunscreen as the frontline protective measure against melanoma is particularly important in light of eight epidemiological studies published between 1979 and 2000 which reported that sunscreen use was a statistically significant risk factor for
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melanoma. The proportion of the adult population avoiding sun exposure in the middle of the day on weekends in Australia increased from 52 to 65 percent from 1991 to 1998. The wearing of hats outdoors has increased from 40 to 50 percent. The wearing of clothes that cover most exposed skin has remained steady at about 45 percent. Older men appear to be at higher risk. While there was a sharp overall increase in the incidence of melanoma in Australia during the mid to late 1980's, mortality in men leveled off and mortality in women declined. Adequate surgical excision of a primary melanoma is essential if early diagnosis is to result in cure. In the surgical treatment of primary melanoma, the respective roles of elective lymph node dissection and sentinel node biopsy have not yet been settled. The Australian clinical practice guidelines recommend considering radiotherapy only under specific circumstances. Biological therapies and vaccines have, as yet, no established place in the management of this disease. Early results from clinical trials of a number of new approaches suggest that biological and immunological treatments for melanoma will win an established place in the management of this disease in the near future. 32 references. •
Participation of Older Males in a Study on Photography as an Aid to Early Detection of Melanoma Source: Australian and New Zealand Journal of Public Health. 24(6):615-618, December 2000. Summary: Researchers conducted a randomized trial of photography as an aid to skin examinations in men over age 50 years. Participants included men from Nelson Bay and Raymond Terrace, New South Wales, Australia, identified from the electoral roll. Of 1,899 men approached, 1,037 agreed to participate, and 973 were photographed. The photographs included all body sites, excluding the legs. Half of the participants received their photographs in the mail, while researchers retained the photographs for the other half. Participants completed a questionnaire about demographic details and risk factors. Of the nonresponders, 29 percent also completed a questionnaire. Eighty-six percent of respondents had risk factors for melanoma, compared to 68 percent of nonresponders, and 47 percent had two or more risk factors, compared to 12 percent of nonresponders. General practitioners conducted skin examinations at years one and two. At year one, 91 percent of the participants remaining in the study regions had been examined. Photographs were lost by only six participants. Participants were more likely to have skin that burned easily, a family history of melanoma, a skin lesion previously treated, and more pigmented lesions on their left arm. The authors conclude that men over the age of 50 years respond to personalized health messages about melanoma and respondents include a high proportion of males with risk factors for melanoma. The researchers conclude that, based on initial results, photography may be a logistically acceptable approach for assisting in the early detection of melanoma. 2 tables, 17 references.
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Total Skin Exams Would Detect 100,000 Hidden Basal Cell Carcinomas a Year Source: Modern Medicine. 64:16; May 1996. Summary: This journal article for health professionals reports on the results of a longterm study on the benefits of skin cancer screening. Findings indicate that patients who develop basal and squamous cell carcinomas are at significantly increased risk of developing malignant melanoma. Results suggest that total skin inspection by physicians would detect an extra 100,000 basal cell carcinomas annually and would help detect melanomas that are still curable.
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Basal Cell Carcinoma: What Dentists Need to Know Source: Journal of the American Dental Association. 130:375-380, March 1999. Summary: Basal cell carcinoma (BCC) is the most common dermatologic cancer and the most common malignancy in white people, with 400,000 new cases reported each year in the United States. It occurs primarily on the head or neck of fair-skinned people who work or spend considerable time outdoors being exposed to ultraviolet (UV) light from the sun. Risk factors for BCC include (1) increasing age, (2) male gender, (3) red or blond hair, (4) blue or green eyes, (5) freckles, and (6) UV exposure. Individuals with BCC are at high risk of developing additional primary lesions. BCC is classified according to clinical and histological characteristics. Common types include (1) nodular, (2) noduloulcerative, (3) superficial, (4) pigmented, (5) morpheaform, and (6) keratotic. Early lesions may be translucent, with raised borders covered by a thin epidermis through which dilated blood vessels can be seen. Treatment options vary with the size and site of the lesion, and the patient's sex and age. Therapeutic options include (1) surgery, (2) curettage, (3) excision, (4) electrosurgery, (5) laser surgery, (6) cryosurgery, (7) Mohs micrographic surgery, and (8) ionizing radiation. Prevention of BCC has focused on reducing UV exposure. There is still no definitive evidence that sunscreens will prevent BCC, although there is evidence that sunscreen use will reduce actinic keratoses. Wearing hats, reducing sun exposure, and using specific sunscreens are recommended. The authors present three cases of orofacial BCC that demonstrate the range of clinical manifestations from small to large lesions. The first two cases, representing the disease's early stages, were much easier to treat than the last case, which was in the late stage. If dentists are aware of the signs and symptoms of BCC, they may be able to recognize it in the early stages during an extraoral examination. With early detection and treatment, BCC can be cured in many people. 6 figures, 28 references.
Federally Funded Research on Skin Cancer The U.S. Government supports a variety of research studies relating to skin 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 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 skin 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 skin cancer. The following is typical of the type of information found when searching the CRISP database for skin cancer:
2 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 (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: 3 D HOLOGRAPHIC VIDEO RECORDING IN BIOLOGICAL TISSUE Principal Investigator & Institution: Nolte, David D.; Physics; Purdue University West Lafayette West Lafayette, IN 479072040 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JAN-2004 Summary: (Adapted from the applicant's abstract): The applicants propose to develop an optical biomedical imaging technique that records real-time video biological tissue, without computed tomography, using compact light sources. This technique uses a newly developed adaptive holographic film that performs as a coherence filter on a video camera, making it possible to image up to 15 mean-free-scattering paths into strongly scattering living tissue near- infrared light (up to 100 um deep into tissue while maintaining 10 um spatially high resolution). The capabilities of the technique will be benchmarked by imaging the three-dimensional structure multicellular spheroids composed of normal and neoplastic cells (tumor spheroids). The spheroids are balls of cells that may be easily cultured in vitro and used to simulate the optical properties of various tissues and nodular tumors. If successful, the proposed research has many biomedical applications. For instance, this technology may be used for dermatological lesion scanning (skin cancer), burn assessment, investigation of internal surfaces through endoscopes or catheters using imagin bundles, and intra-operative procedures giving a physician immediate video images of tissue beneath the surgical surface. Because of the immediate high-speed nature of direct imaging, this technology will be particularly attractive for fast dynamic studies and making movies of processes inside tissue such as portions of the cardiovascular system requiring high time resolution, or for metabolic imaging of tumors and the rapid uptake of tagged optical markers. This optical tissue imaging technology will be unique in its combination of high time resolution with high spatial resolution, and therefore represents a unique biomedical imaging technology with significant potential for down-stream development for cancer imaging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: A NON INVASIVE DERMATOLOGICAL LESION CLASSIFIER Principal Investigator & Institution: Craine, Eric R.; Western Research Company, Inc. 2127 E Speedway, Ste 209 Tucson, AZ 85719 Timing: Fiscal Year 2001; Project Start 01-NOV-1998; Project End 31-MAY-2002 Summary: Skin cancer is the fastest growing cancer. Approximately 34,100 Americans developed cutaneous melanoma in 1995; of the survivors, many must contend with the ongoing trauma of disfigurement and fear. Skin biopsies are now the most frequently performed medical procedure. It is axiomatic among dermatologists that early detection and diagnosis are critical. Great strides have been made in early detection of suspect skin lesions; however failure to biopsy the right lesion has severe consequences. The dilemma is exacerbated since 50- 80 percent of biopsies prove unnecessary, contributing to an enormous waste of health care dollars, patient trauma and negative patient behavior feedback. The Phase I work in dermatological spectroscopy and artificial neural net technology suggest that an automated clinical diagnostic aid which produces a quantitative rather than qualitative diagnostic assessment of skin lesions is possible. This project proposes development and testing of such a product. During Phase II a large number of spectroscopic samples of melanoma and nevi will be used to complete development of an artificial neural net classifier. Such a classifier system will lead to a commercial product to discriminate "normal," pre-cancerous and cancerous skin lesions. PROPOSED COMMERCIAL APPLICATION: The proposed project will lead to a non-
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invasive, in-office, real-time test to provide an automated, repeatable diagnostic probability of the nature of skin lesions prior to biopsy. Skin biopsies are now the most frequently performed reimbursed Medicare procedure, and as many as 50-80% are found not to be necessary after the fact. The low cost of this test, and rapid amortization of the system, coupled with the enormous health care cost savings possible in conjunction with a significant and widely recognized health problem, suggest that this product could have great commercial potential. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADENOVIRUS RECEPTOR CAR IN EPITHELIAL MALIGNANCIES Principal Investigator & Institution: Korn, Michael C.; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2003; Project Start 06-MAR-2003; Project End 28-FEB-2008 Summary: (provided by applicant): The objective of the proposed work is to improve the treatment of epithelial malignancies with recombinant adenoviruses by restoring expression of the Coxsackie- and Adenovirus Receptor (CAR) at the surface of cancer cells. This molecule is the primary receptor for adenovirus and mediates initial attachment of the virus to target cells. Its expression is frequently reduced in cancer cells. The proposed project will explore the hypothesis that loss of CAR expression in cancer cells is the consequence of constitutive activation of the Ras/MAPK and TGFbeta signal transduction pathways resulting in repression of CAR gene transcription and alteration of the subcellular localization of CAR protein. To characterize alterations of the subcellular localization of CAR in response to Ras/MAPK and TGF-beta signaling, techniques for labeling surface proteins and cell fractionation will be utilized. This approach will be complemented by generating CAR-GFP fusion proteins, acting as reporter molecules for the assessment of alterations in CAR localization upon perturbation of signaling. Furthermore, changes of the composition of protein complexes containing CAR and concomitant modifications of the molecule will be assessed. To identify regulatory elements mediating CAR transcription in response to such signaling events, the regulatory region of the CAR gene will be defined. Luciferaseexpressing reporter constructs containing the regulatory region will then be generated and, guided by computer-assisted sequence analysis, progressively mutated to identify relevant sequence elements. Binding of candidate transcription factors will be confirmed by mobility shift assays. The impact of Ras/MAPK and TGF-beta signaling will then be studied in a mouse model of skin cancer. Pharmacological inhibitors of both pathways will be administered and the resulting effect on CAR transcription and subcellular localization will be assessed. Finally, non-replicating recombinant adenoviruses expressing a reporter protein will be administered in conjunction with inhibitors of signaling to measure their impact on adenovirus entry into normal and cancer cells in vivo. Collectively, results from these studies will reveal detailed knowledge about the molecular link between CAR and the Ras/MAPK and TGF-beta signaling networks and explore the possibility of restoring CAR expression on cancer cells by pharmacological inhibition of these signaling circuits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANAPLASIA & DIFFERENTIATION IN A REVERSIBLE CANCER MODEL Principal Investigator & Institution: Murphy, Daniel J.; Anatomy; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122
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Timing: Fiscal Year 2003; Project Start 11-JUN-2003; Project End 10-JUN-2006 Summary: (provided by applicant): A reversible transgenic mouse model for skin cancer will be used to investigate the relationship between neoplasia and anaplasia, with the long term goal of better understanding the consequences of oncogene activation and inactivation for differentiation. The specific aims are 1) to test the hypothesis that neoplastic INV-MycERTM keratinocytes will differentiate upon removal of ectopic Myc function; 2) to identify the in vivo alterations in keratinocyte gene expression upon activation and subsequent deactivation of c-MycERTM; 3) to engineer a ubiquitously prospective, conditionally expressed, regulatable c-Myc transgenic mouse. IHC and ISH will be employed to assess the differentiation state of INV-MycERTM keratinocytes in SA1 while tissue microdissection coupled with high throughput microarray analysis will define the transcriptional basis for Myc-induced change in SA2. For SA3, the MycERTM transgene, linked by way of an IRES to EGFP and preceded by a floxed Stop cassette, will be targeted to a ubiquitously active locus by homologous recombination. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AP-1 AND CHEMOPREVENTION NONMELANOMA SKIN CANCER
OF
UV
INDUCED
Principal Investigator & Institution: Bowden, G T.; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2001 Summary: The hypothesis to be tested in this project is that sustained induction of the transcription factor complex, AP-1, plays a functional role in UVB induced skin tumor promotion and the development of non-melanoma skin cancers. UVB irradiation of keratinocytes can result in both genotoxic initiating events including mutational activation of oncogenes and inactivation of tumor suppressor genes as well as epigenetic, promotional events such as induction of genes involved in cell proliferation and apoptotic cell death. UV irradiation of cells can bring about the transient activation of a number of transcription factor complexes including AP-1, NF-kappaB and p26TCF/elk-1. The focus of this proposal is on the complex, AP-1 and whether its induction plays a functional role in UVB induced promotion of non-melanoma skin cancers. AP-1 activation and enhanced expression of certain genes have been investigated in relation to cell proliferation and apoptotic cell death, biological effects of UVB that can play a role in tumor promotion. UVB irradiation could mediate both of these biological effects in keratinocytes through AP-1 activation. Based on preliminary studies in which we have shown in keratinocytes that UVB induces both AP-1 DNA binding and AP-1 transactivation., we are developing chemopreventive strategies using pharmacological agents that block AP-1 activation mediated by UVB. The agents of interest include retinoids, perillyl alcohol, a tea polyphenolic, epigallocatechin gallate (EGCG) and aspirin. The specific aims to address the hypothesis are: 1) to determine whether the expression of a dominant negative c-jun mutant protein in the epidermis of transgenic mice will block UVB induction of non-melanoma skin tumors by blocking AP-1 activation; 2) to determine whether atypical PKC's (PKCzeta and PKCgamma) are involved in UVB-induced c-fos transcription and AP-1 activation in cultured human keratinocytes and whether one or more of the MAP kinases (ERK1/2, JNK1/2, p38) are also involved in UVB-induced c-fos transcription; 3) to determine whether certain retinoids, perillyl alcohol or epigallocatechin gallate (EGCG) and aspirin can block UVBinduced AP-1 activation in cultured mouse and human keratinocytes, and in the mouse epidermis; 4) to determine whether certain retinoids, perillyl alcohol or aspirin can
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inhibit UVB induced mouse skin tumor formation. These preclinical studies are designed to lead to the development of new strategies for the chemoprevention of human non- melanoma skin cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ARSENIC AND HEALTH IN BANGLADESH Principal Investigator & Institution: Christiani, David C.; Professor; Harvard University (Sch of Public Hlth) Public Health Campus Boston, MA 02460 Timing: Fiscal Year 2001 Summary: (Taken from application) Exposure to arsenic has been associated with the induction of cancer in humans. It is widely accepted that arsenic can cause nonmelanoma skin cancers (in particular, squamous-cell carcinoma). In addition, arsenic may be an important cause of bladder, lung, lung, and other internal cancers. We propose to study biomarkers of exposure, skin lesions, skin and bladder cancer, and heritable susceptibility in two populations: one in Taiwan, where remediation efforts have resulted in a reduction in arsenic exposure to ranges of one to three-hold in most US communities; and a second population in Bangladesh, an area recently described with extremely high exposures from drinking-water contamination. We propose a population-based approach, incorporating markers of exposure (drinking-water arsenic, toenail arsenic), susceptibility (genetic polymorphisms in metabolizing genes), and outcome (squamous-cell carcinoma of the skin, bladder, cancer, non-malignant skin lesions) in order to test several hypotheses important to advancing our understanding of the human-health consequence of arsenic exposure. We will conduct a repeat-measures study, designed to evaluate biologic markers including toenail concentrations, methylated arsenic compounds in the urine, and genetic traits. We will also conduct two case-control studies of skin and bladder cancer: one an extension of our ongoing work in Taiwan and the other in Bangladesh. These studies are designed to fill important research gaps in our understanding of arsenic and human health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ARSENIC INDUCED SIGNALING PATHWAYS IN HUMAN EPIDERMIS Principal Investigator & Institution: Abdel-Malek, Zalfa A.; Research Professor; University of Cincinnati 2624 Clifton Ave Cincinnati, OH 45221 Timing: Fiscal Year 2001; Project Start 01-APR-1995; Project End 31-MAR-2005 Summary: (Taken from application) Toxicity due to exposure to high levels of arsenic through dietary, occupational, or medicinal routes has been well documented in different countries. The most obvious and prevalent manifestations of arsenic toxicity are the cutaneous changes that involve hyperkeratosis and increased pigmentation, and latent basal and squamous cell carcinoma. The latter two types of skin cancer differ from the sun induced skin cancer tumors in that they occur mainly on the palms and soles, rather than on sun exposed anatomical sites, and are more invasive and metastatic. Although arsenic induced cutaneous alterations are histologically well characterized, the molecular mechanisms by which they arise are poorly understood. In particular, the mechanisms by which arsenic affects genomic DNA and induces the expression or suppression of specific genes are for the most part unknown. Given that the skin is the first interface between the human body and the environment, and that cutaneous manifestations often reflect internal organ dysfunction, it is important to elucidate the mechanism of action of arsenic on human skin. There is sufficient evidence
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to support the notion that arsenic induces oxidative stress in mammalian cells. In the cutaneous epidermis, increased keratinocyte proliferation that leads to hyperkeratosis and eventually cancer tumors, as well as hyperpigmentation, may be the outcome of arsenic induced oxidative stress in keratinocytes and melanocytes, respectively. We are proposing to investigate the hypothesis that arsenic induced cutaneous alterations result from oxidative stress that disrupts normal epidermal cell proliferation and differentiation. For this, we will use primary cultures of normal human melanocytes and keratinocytes, as well as a skin substitute model that mimics the skin in situ. The effects of arsenic on genes involved in regulating keratinocyte proliferation and differentiation, and melanocyte pigmentation will be elucidated. The above in vitro models represent an optimal approach to elucidate the mechanism of action of arsenic on human cells and tissues. The results to be obtained should be relevant to other epithelial tissues, such as lung and bladder tissues, that are affected by arsenic. The studies hereby proposed should set the stage for further investigations of the mechanisms by which arsenic might promote the effects of other environmental carcinogens, such as ultraviolet radiation and polycyclic aromatic hydrocarbons. The outcome of this proposal should lead to more effective means for intervening in, and treating the manifestations of arsenic toxicity, and for setting more effective policies regarding safe levels of arsenic exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ATYPICAL NEVI IN MELANOMA--A CASE-CONTROL STUDY Principal Investigator & Institution: Titus-Ernstoff, Linda T.; Associate Professor; Community and Family Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, NH 03755 Timing: Fiscal Year 2001; Project Start 01-APR-1996; Project End 31-JAN-2002 Summary: Despite substantial interest in atypical nevi as melanoma risk factors and precursors, little is known about risk factors for these lesions, or their role in melanoma etiology. Previous case-control studies that have assessed atypical nevi as melanoma risk factors were small and/or clinic based. Similarly, only a few small, clinic-based studies have examined risk factors for atypical nevi. Our primary aims are to 1) conduct a large, population-based, case-control study of nonfamilial melanoma to evaluate atypical nevi, benign nevi, sun sensitivity, and solar exposure as risk factors, and 2) conduct a large, population-based evaluation of risk factors for atypical nevi. In separate analyses, we will explore risk factors associated with melanoma subgroups based on a) presence or absence of atypical nevi, and b) tumor histologic type. As a tertiary aim, we propose a validation substudy that will evaluate whether subjects can accurately selfdiagnose atypical nevi. At least 535 cases of melanoma, ascertained through the NH State Cancer Registry, will be enrolled over a five year study period. We will enroll 800 population controls identified from drivers' license lists (age 65 or less), and medicare beneficiary lists (age greater than 65). Consenting subjects will complete a telephone interview, conduct skin self-examination, and participate in a dermatologist-conducted skin examination. Based on the dermatology examination, all subjects will be classified as "with" or "without" atypical nevi. Our statistical approach will include two primary case-control analyses to evaluate 1) risk factors for melanoma, and 2) risk factors for atypical nevi. In addition, we will conduct separate case-control comparisons to explore risk factors for specific melanoma subsets. Our approach will elucidate the etiology of melanoma, and identify risk factors for atypical nevi. Finally, we will evaluate subjects' ability to self-screen for atypical nevi by comparing the results of self-examination to the results of the dermatologist examination. The ability to self-diagnose atypical nevi has important implications for melanoma prevention.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOLOGIC APPROACH TO THERAPY OF AGGRESSIVE SKIN CANCER Principal Investigator & Institution: Lippman, Scottm; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2001 Summary: Standard local treatment of aggressive squamous cell carcinomas (SCC) of the skin continues to be plaqued with primary disease recurrence and second primary tumors in most patients afflicted with these cancers. In addition to substantial mortality rates, cosmetic, psychologic and functional impairment are frequent and devastating sequelae of aggressive skin cancers and the required definitive local therapy. Using our prospective skin cancer database, four clinical-histologic criteria (depth of invasion, perineural invasion, lesion size, regional metastases) define a population of patients at greater than 70% risk of local, and/or regional recurrence after definitive local/regional therapy. Second primary tumors (SPTs) occur at a rate approximating 6% per year. Single-agent therapy with retinoic acid or alpha-interferon have limited activity in the therapy of advanced solid tumors. However, both of these agents are known to possess antiproliferative, differentiative, anti-angiogenic and immunomodulatory properties; probably exerting these effects through separate molecular mechanisms. Ongoing mechanistic studies have indicated some potentially important anticancer interaction sof retinoid-interferon combinations. In vitro studies of retinoid-interferon-alpha combinations indicate a synergistic interaction in the induction of interferon-stimulated gene factor and several interferon inducible enzymes (e.g., 2'-5' oligoadenylate synthetase) and programmed-cell death. In vivo studies have found synergistic inhibition of experimental tumor induced angiogenesis. Clinical studies include two recent phase II trials of 13-cis retinoic acid (13-cRA) in combination with alphainterferon which have reported major responses rates of 50% and 68% in advanced skin SCC. Based on the substantial preclinical and clinical experience, we now propose an adjuvant chemoprevention study using these agents for six months in patients with aggressive squamous carcinoma of the skin treated with standard surgery and radiation therapy. This chemopreventive and therapeutic approach is designed to decrease the development of primary disease recurrence (local, regional and distant) as well as SPTs, in a controlled, randomized trial. A number of correlative laboratory and mechanistic studies aimed at understanding several major aspects of the mechanisms of action of retinoids and interferon are included within this clinical trial. In addition, we will obtain, through self-administered questionnaires, outcome information on these SCC patients relative to emotional well-being, quality of life, cognitive functioning, and pain in order to develop longitudinal profiles of these outcome parameters. A total of 90 patients, meeting these high risk criteria, will be required for the study with a minimum follow-up of three years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOLOGY OF NONMELANOMA SKIN CANCER GROWTH & PROGRESSION Principal Investigator & Institution: Clayman, Gary L.; Associate Professor; Immunology; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 06-MAY-1996; Project End 31-MAR-2004
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Summary: The incidence of non-melanoma skin cancer (NMSC) is increasing rapidly, and further increases are expected. A small proportion of these basal and squamous cell carcinomas of the skin exhibit an aggressive phenotype, characterized by multiple recurrences, size more then 2 cm, invasion of muscle, cartilage, bone, or nerves, or lymph node metastasis. The State of Texas has a high incidence of skin cancer and an unusually high death rate from NMSC. Because of its geographic location and referral patterns, the University of Texas M. D. Anderson Cancer Center treats a large number of highly aggressive NMSC; in fact, nearly half of the approximately 100 new cases of skin cancer seen annually in the Department of Head and Neck Surgery exhibit aggressive behavior and are difficult to control by surgery and radiation. Progress toward reducing the incidence of and morbidity and mortality from NMSC requires a 3-pronged approach; Identification of the etiologic and genetic factors that contribute to skin cancer induction; determination of the host and tumor characteristics associated with skin cancer progressions; and development of new approaches for the treatment of highly aggressive NMSC. The specific aims of this Program are therefore, to (1) develop an understanding of the molecular events leading to skin cancer development; (2) ascertain athe role of UV radiation in the development of NMSC, including those with aggressive behavior, (3) assess the contribution of various mechanisms to progression of NMSC; (4) reduce morbidity and mortality and improve the quality of life of patients with aggressive skin cancer. These goals will be addressed by 16 Key Program Investigators in laboratory and clinical investigations on the role of p53 in UV carcinogenesis and immunosuppression (Project 1); regulation of apoptosis in skin cancer development (Project 2); DNA repair and chromosome instability in skin cancers (Project 3); and adjuvant biotherapy of aggressive skin cancers with 13-cis retinoic acid and interferon-alpha (Project 5). These studies will be coordinated and supported by cores devoted to collection of clinical, pathological, molecular, and epidemiological data and procurement, maintenance, processing, and distribution of clinical samples and biostatistical analysis and integration of laboratory and clinical data. These efforts will be supported by 16 collaborators/co-investigators and 8 Program Advisors. The Program Project will provide information on the etiology, biology, pathogenesis, and mechanisms of induction of NMSC and generate valuable clinical and epidemiological databases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CANCER CHEMOPREVENTION--ROLE OF INFECTION/IMMUNITY Principal Investigator & Institution: Loprinzi, Charles L.; Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAR-2004 Summary: Over the past decade, a substantial body of data has accumulated which implicates the human papillomaviruses (HPVs) in epithelial cancers, especially cervical cancer. More recently, a new family HPV has been identified in skin cancers that are related to those found originally in patients with heritable skin cancer prone condition, epidermodysplasia verruciformis. With the advent of new chemoprevention strategies directed against each of these cancer types, it appears prudent to develop novel secondary endpoint biomarkers (SEBs). Accordingly, a central Theme of this project is to develop HPV-related SEBs in the context of two novel chemoprevention strategies, one of which is expressly directed against HPV infection. Two Phase II chemoprevention clinical trials are planned at the Mayo Clinic and in the North Central Cancer Treatment Group (NCCTG) member institutions, with support for protocol development, data management, and statistical analysis deriving primarily from NCCTG CCOP grants ( i.e.
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research base and individual institution grants). The first is a randomized pilot evaluation of topical imiquimod, and immunomodulatory agent which has proven to be safe and effective for the treatment of genital warts. This trial will be conducted on patients with recurrent and/or high-grade cervical intraepithelial neoplasia (CIN). For skin cancers. This trial will attempt to reproduce and further substantiate a previous randomized trial in the which a treatment benefit was demonstrated. Broad-range PCR techniques will be used to monitor the type-specific persistence of HPV in cervical specimens after imiquimod therapy. Similar techniques will be used to characterize the potential role of HPV in skin cancers, strategies will also be developed to determine if HPV - specific immune responses can be used as SEBs in CIN related gene expression and AP-1 expression/activity will be developed for the skin cancer chemoprevention project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CARDINAL BERNARDIN CANCER CENTER, LOYOLA UNIVERSITY Principal Investigator & Institution: Petruzzelli, Guy J.; Professor, Dept. of Otolaryngology; None; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, IL 60611 Timing: Fiscal Year 2001; Project Start 10-AUG-1998; Project End 31-JUL-2003 Summary: The Cardinal Bernardin Cancer Center of Loyola University Chicago under the direction of Richard I. Fisher, M.D. is applying for a P-20 Cancer Center Planning Grant. The Center is a 35 million dollar, 125,000 sq. ft. facility that provides state-of-theart clinic facilities to house all of Loyola's outpatient cancer care, 34 new research laboratories to expand the basic/translational science research base, space for core facilities, offices for all faculty engaged full-time in cancer related activities, and administrative and educational space for campus and community outreach activities. The Cancer Center Director has responsibility for allocation of all clinical and laboratory space in this facility, recruitment of new research faculty, and administration of the institutional operating budget. In 1996, the clinical program served more than 10,000 patients with over 45,000 patient visits, representing an increase of 10-15 percent per year. During the last five years, Loyola affiliated hospitals had 1408 patient registrations onto clinical research protocols. The center currently has four unique Research Programs: 1) Hematologic Malignancy led by Drs. Manuel Diaz and Richard Fisher integrates genetic and clinical studies of leukemias and lymphoma; 2) Cancer Immunology led by Drs. Katherine Knight and Martin Kast integrates basic and applied tumor immunology; 3) Skin Cancer led by Dr. Brian Nickoloff integrates basic and clinical studies of cutaneous malignancies; and 4) Cancer Cause and Prevention led by Drs. Richard Cooper, Kathy Albain, and Robert Flanigan develops cancer prevention and control initiatives targeted toward prostate and breast cancer, especially in the minority communities. Current annual federal funding of Cancer Center investigators exceeds 8,300,000 dollars. This planning grant will be a critical milestone for the Cancer Center and will enable it to continue its rapid growth and development by completing necessary recruitment of the eleven remaining Cancer Center research faculty positions, developing needed core facilities, expanding interdisciplinary faculty meetings and seminars, and stimulating new translational research initiatives. At the completion of this grant, the Cardinal Bernardin Cancer Center plans to be positioned to successfully apply for a P-30 Cancer Center Support Grant. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHEMOPREVENTION RESVERATROL
OF
PHOTOCARCINOGENESIS
BY
Principal Investigator & Institution: Ahmad, Nihal; Assistant Professor; Medicine; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2004 Summary: (provided by applicant): In the United States, non-melanoma skin cancer that includes basal- and squamous-cell carcinoma is the most frequently diagnosed form of cancer and, according to an estimate, more than a million new cases of skin cancers are diagnosed annually in the USA. Therefore, it is warranted to intensify our efforts for the development of novel approaches for prevention and therapy of this cancer type. Chemoprevention by naturally occurring non-toxic compounds is a potential strategy to prevent the occurrence of the disease. Resveratrol (3,5,4'-trihydroxystilbene), a phytoalexin antioxidant found in grapes, red wines, berries and peanuts has been shown to afford cancer chemopreventive effects in chemically-induced murine skin carcinogenesis. The classical chemical carcinogenesis model of skin cancer is regarded to have little, if any, relevance to humans skin cancers because the excessive exposure to solar ultraviolet (UV) radiation is the major cause of human skin cancers. Our preliminary studies have shown that topical application of resveratrol prevents against chemically induced skin carcinogenesis in SENCAR mice. The molecular mechanism(s) of the biological effects imparted by resveratrol is not well understood. Our recent studies (Clinical Cancer Research, accepted for-publication), have demonstrated that resveratrol treatment to human epidermoid carcinoma (A431) cells results in an induction of the cyclinkinase inhibitor WAFl/p21 that inhibits cyclin (D1/D2)-cdk 6, cyclin (D1/D2)-cdk 4, cyclin E-cdk 2 complexes, thereby resulting in a G1-phase arrest of the cell cycle and an apoptotic death of the cells. We have also found that resveratrol treatment causes a modulation in refinoblastoma (pRb)-E2FDP machinery, during G1phase arrest and apoptosis of A431 cells. The current application is based on these novel observations, and is designed to investigate the chemopreventive potential of resveratrol against UVB-mediated skin carcinogenesis, and the molecular mechanism(s) by which this food-based polyphenolic antioxidant imparts cancer chemopreventive effects. The central hypothesis of the work proposed in this application is that resveratrol will impart chemopreventive effects against photocarcinogenesis via modulating cki-cyclin-cdk network-mediated cell cycle regulation and apoptosis. In this study, we will first establish cancer chemopreventive potential of resveratrol against UVB-mediated damages including skin tumorigenesis in SKH-1 hairless mice. We will then conduct studies to assess the involvement of cki-cyclic-cdk network as a mechanism of chemopreventive effects of resveratrol during for UVB-mediated responses and skin tumorigenesis in SKH-1 hairless mice. Successful completion of this application will define i) the chemopreventive/therapeutic potential of resveratrol against skin cancer, and ii) molecular mechanism(s) of the biological effects of Resveratrol. This may pave the way for the development of novel strategies for prevention and possibly treatment of skin cancer and other epithelial cancers as well. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMOPREVENTION OF SKIN CANCER PROGRAM PROJECT Principal Investigator & Institution: Alberts, David S.; Professor of Medicine and Pharmacology; None; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2001; Project Start 22-JUL-1980; Project End 30-JUN-2003
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Summary: It is estimated that there will be more than 900,000 new cases of nonmelanoma skin cancer (NMSC) diagnosed in the U.S. in 1997, accounting for approximately 40% of all cancer diagnoses. melanoma will account for 1-3% of new cancer cases (40,300 cases in 1997) but the incidence and mortality rates are increasing more rapidly than any other invasive cancer. Continued increases in NMSC are expected as the population ages and as larger amounts of UV radiation reach the earth's surface because of the depletion of the ozone layer. The overall goal of our Chemopreventative of Skin Cancer Program Project is to develop safe and highly efficacious intervention strategies for prevention of melanoma and non-melanoma skin cancers and to develop basic science and clinical research approaches which will serve as models for the chemoprevention of a wide range of human epithelial cancers. Our Program Project consists of four scientific research components designed by an outstanding group of dedicated skin carcinogenesis scientists to address our primary hypothesis-that chemopreventive agents can alter the natural history of skin cancer. Preclinical studies of mechanisms of UV-induced carcinogenesis and mechanisms of action of topically applied chemoprevention agents in melanoma and NMSC animal models. Clinical studies to establish the validity and reproducibility of histopathologic, morphometric, genetic, and immunohistochemical surrogate endpoint biomarkers, in participants with preclinical actinic keratoses, actinic keratoses, cutaneous squamous cell cancers, and dysplastic nevi. Sequential phase IIa and IIb randomized doubleblinded, placebo- controlled skin cancer prevention studies of chemoprevention agents selected because of their mechanistic effects on the skin carcinogenesis signal transduction pathway as well as documented activity in UVB skin carcinogenesis and transgenic melanoma animal models. In depth evaluation of possible correlations between changes in histopathology/morphometry and alterations in genetic expressions (as evaluated by cDNA microarray and immunohistochemical assays in human epidermal tissue biopsies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMOPREVENTION OF DIFLUOROMETHYLORNITHINE (DFMO) PHASE
SKIN
CANCER:
Principal Investigator & Institution: Carbone, Paul P.; Director; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMO-PREVENTION CARCINOMAS
OF
UVB-INDUCED
BASAL
CELL
Principal Investigator & Institution: Athar, Mohammad; Dermatology; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Solar UVB radiation is a well-known major risk factor for the induction and development of non-melanoma skin cancers (NMSCs), which include both basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs). The carcinogenic effects of environmental UVB exposure are thought to retard the direct induction of structural changes in DNA, such as cyclobutane pyrimidine dimers and 6-4 photoproducts, leading to mutations in the form of C to T and CC to TT transitions (UVB signature mutations). These mutations are present in the p53 gene of the majority
Studies 51
of SCCs, BCCs, actinic keratoses and in non-tumor skin adjacent to these lesions. Skin BCCs are the most common form of human cancer, affecting at least 750,000 Americans each year. The molecular mechanism of BCCs induction involves activation of the sonic hedgehog (shh) pathway. Extensive experimental evidence confirms that cutaneous UVB exposure induces UVB signature mutations both in p53 and in ptch genes, which together likely play an important role in blocking apoptosis and augmenting proliferation and clonal expansion of initiated cells leading to BCCs induction of BCes. We propose that rescuing mutant p53 and blocking shh pathway activation together using a combinatorial approach in ptchheterozygous mice could provide additive and/or synergistic protection against BCCs. To test this hypothesis, we will employ a genetically engineered murine model of BCCs development and use combination of a rescuer of mutant p53 conformation and function, CP-31398 and a specific inhibitor of the shh pathway, cyclopamine. It is our belief that this animal model combined with the study of chemical agents capable of rescuing mutant p53 and inhibiting shh pathway activation provides a uniquely effective approach for testing innovative mechanismbased strategies for the chemoprevention of NMSCs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMOPREVENTIVE PROPERTY OF LUNASIN-ENRICHED SOY EXTRACT Principal Investigator & Institution: Galvez, Alfredo F.; Filgen Biosciences, Inc. 2333 Courage Dr, Ste C Fairfield, CA 94533 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2003 Summary: (provided by applicant): The synthetic form of a chromatin binding peptide derived from soy, named lunasin, has been discovered to prevent the transformation of normal cells to cancerous foci induced by chemical carcinogens and viral oncogenes. Lunasin has the potential to be a general cancer preventative and could explain epidemiological associations between soy consumption and reduced cancer incidence. Lunasin is found in the water soluble fractions of soy protein preparations and can be extracted by standard purification methods, making it cheaper to commercially produce than chemical synthesis or recombinant DNA. The objective of the proposed research is to extract soy protein fractions that contain biologically active levels of lunasin and use them to develop cancer preventive products. This can be accomplished by first, extracting and purifying lunasin at increasing levels from soy protein preparations, then testing the lunasin-containing fractions in cell transformation assays using chemical carcinogens and viral oncogenes as cancer inducing agents. The most effective lunasinenriched soy fraction will then be encapsulated in a liposome-based dermal formulation and used in a mice skin cancer study to determine in vivo efficacy in preventing skin tumor formation. Once efficacy of the lunasin topical formulation is determined, preclinical and clinical testing for safety and efficacy in preventing skin cancer formation and progression will commence as part of a SBIR Phase Il study. This will eventually lead to the development of lunasin-based topical products such as skin creams, lotions and sunscreen against skin cancer. With approximately one million cases of skin cancer being diagnosed each year and with the aging demographics of the baby boom generation, these chemopreventive products should have a market potential of more than 100 million customers by the year 2003. The proposed research also lays the groundwork for the development of lunasin-based chemopreventive products against other common cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CLINICAL PHASE I TESTING WITH PHTHALOCYANINE FOR SKIN MALIGNANCIES Principal Investigator & Institution: Kinsella, Timothy J.; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2002 Summary: (Applicant's Description) The overall objective of Project 4 is to design and initiate the first hypothesis-driven clinical trial(s) of the silicon phthalocyanine photosensitizer PC 4 in photodynamic therapy (PDT) of human cancers. The project is based on extensive in vitro and in vivo testing performed at CWRU during the last funding period. The National Cancer Institute's (NCI) Drug Decision Network (DN) has also contributed significantly to the pre-clinical testing of Pc 4-PDT, including pharmacokinetic studies in mice and IND-directed toxicology studies in two animal species. Based on CWRU and NCI DN data, we hypothesize that Pc 4-PDT will be effective in the treatment of primary and metastatic skin cancers without severe local or systematic toxicity including cutaneous photosensitivity. We also hypothesize that a mechanism of Pc 4-PDT-related tumor response in humans involves cell death by apoptosis. To test these hypotheses, we have designed a Phase I and translational study of Pc 4-PDT in selected patients with primary and metastatic skin cancers, which will be completed in years 1-3 of this project. The specific aims are: (1) To conduct a two-part Phase I dose escalation trial to determine the maximum tolerated dose and dose-limiting toxicities of PDT with intravenously administered Pc 4; (2) To determine the pharmacokinetics of Pc 4 following a two-hour i.v. infusion in humans; (3) To monitor normal and tumor tissues in patients for clinical, histological, and biochemical endpoints of PC 4-PDT-related toxicity and cell death mechanisms; (4) To observe patients for a clinical anti-tumor response to Pc 4-PDT; and (5) Based upon the results of the first Phase I study described in Specific Aims 1-4, to design for years 3-5 of this program: (a) a Phase II trial of Pc 4-PDT in patients with recurrent and locally invasive basal and squamous cell skin carcinomas using the recommended dose schedule of Pc 4 and light determined in the Phase I trial; and (b) a Phase III trial of Pc 4-PDT for locally recurrent esophageal cancers. In the clinical trials of Specific Aim 5, in addition to cleavage of poly(ADP-ribose) polymerase, other biochemical markers of Pc 4-PDT tumor responses will be tested for clinical relevance based on promising experimental data from Projects 2 and 3. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CLUE CARCINOGENESIS
STUDIES--EVALUATING
BIOMARKERS
OF
Principal Investigator & Institution: Helzlsouer, Kathy J.; Professor; Epidemiology; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 17-MAY-2000; Project End 28-FEB-2005 Summary: Resources and methods to rapidly evaluate the clinical utility of promising biomarker of risk and disease are critically needed. Preliminary assessment of promising serologic and genetic markers may be performed using available specimen banks. The proposed study will use an existing community-based cohort under follow-up for cancer outcomes. Participants donated blood specimens in 1974 (CLUE I) and 1989 (CLUE II). Serum/plasma, red blood cells and buffy coats have been stored at -70 degrees Centigrade 1989. As a member of the Early Detection Network we propose to set aside alliquots serum/plasma, red blood cells and DNA from existing cohort resources (over 58,000 specimens) as a network resource. We will expand the resource
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by collecting tissue specimens from Cohort participants who develop cancer. We propose to conduct another blood collection campaign in the year 2001. To obtain 40,000 blood specimens, encouraging previous CLUE participants to donate again. This will provide specimens on individuals from multiple time points and expand the cohort resources. To demonstrate the ability to rapidly and efficient evaluate multiple types of biomarkers for the early detection of cancer or markers of developing cancer we propose to study three promising biomarkers: Fatty acid synthase concentrations (FAS), a potent8ial marker for the early detection of aggressive forms of breast cancer; genetic polymorphisms in the XPD gene, a potential marker of susceptibility to the development of a second primary cancer among individuals with non-melanoma skin cancer; and tobacco-specific nitrosamine hemoglobin adducts (TSNA), a potential marker of risk for the development of lung cancer among smokers. The CLUE study cohorts will provide a mechanism to rapidly assess potential markers and aid in their transition from the laboratory to the clinical setting. The long-term characterization of the cohort and having multiple specimens are valuable for determining the validity (sensitivity and specificity) of biomarkers, changes in biomarkers over time, association with early vs late stages of carcinogenesis and assessing latency periods. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COHORT STUDY OF HEALTH EFFECTS OF AS EXPOSURE ON BANGLADESH Principal Investigator & Institution: Ahsan, Habibul; Associate Professor; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001 Summary: Evidence of the health effects of inorganic arsenic (InAs) comes from ecological or retrospective studies. The overall goal of this proposal is to assemble a large cohort of adults to prospectively examine the short-term and intermediate-term health effects of such exposure, with an initial focus on skin lesions, skin cancers, biomarkers of As toxicity, and mortality. The creation of this cohort will also facilitate Project #4 which will study pregnancy outcomes and children's health in the same families. Ultimately this cohort serves as the base for future studies of long-term health effects of InAs exposure. We propose to recruit an follow 10,000 married men and women from Sonargaon, Bangladesh who have been exposed to a wide range of InAs (from 1000 mug/L) in drinking water. Interview data, blood and urine samples will be collected by trained personnel at the baseline. Follow-up interviews with the subjects will be conducted in year 3 in year 5. Incidences of skin lesions and skin cancers will be ascertained through physical examination by the study physicians followed by histopathologic confirmation be the study pathologist. The proposed study will be the first to prospectively examine the full dose-response relationship between arsenic exposure and skin lesions and skin cancers using individuals measurement data. The study will also examine the biomarkers, urinary arsenic species and TGFalpha, in relation to arsenic exposure (cross-sectionally in the baseline cohort) and in relation to the risk of skin lesions and skin cancers (prospectively using a case-cohort design nested within the total cohort). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COMBINED PREVENTION
NATURAL
INHIBITORS
IN
SKIN
CANCER
Principal Investigator & Institution: Slaga, Thomas J.; Scientific Director; Amc Cancer Research Center 1600 Pierce St Denver, CO 80214
54 Skin Cancer
Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The overall goal of this proposal is to determine the mechanism(s) of synergistic action of the natural source compounds, known to inhibit one or more stages of skin carcinogenesis, i.e., initiation and promotion/progression. Our hypothesis is that concurrent topical and systemic (i.e., dietary) treatment with selected natural source inhibitors of different stages of skin carcinogenesis result in synergistic effects leading to more efficient prevention of skin cancer. The inhibitors to be tested include ellagic acid, proanthocyanidin B-2-gallate, N-acetylcysteine, calcium D-glucarate, lycopene, ursolic acid from rosemary extract, and resveratrol. We propose to initially utilize a number of very predictive short-term in vitro and in vivo tests in order to identify the mechanism(s) and to differentiate the potencies of selected inhibitors at various concentrations under standard conditions. The most effective compounds will then be studied in long-term tumor experiments utilizing a 7,12dimethylbenz[a]anthracene (DMBA)-initiated, 12-O-tetradecanoylphorbol-13-acetate (TPA)- promoted multistage carcinogenesis model in SENCAR mice and an ultraviolet light (UV)-initiated, TPA-promoted multistage carcinogenesis model in SKH-1 mice. Finally, combinations of the best anti-initiating and anti-tumor promoting agents will be tested in the DMBA-initiated, TPA-promoted skin carcinogenesis model in SENCAR mice as well as in the UV-initiated, TPA-promoted skin carcinogenesis model in SKH-1 mice. The following Specific Aims will be studied: (i) identification, using various very predictive short-term in vitro and in vivo tests, including the DMBA-induced inflammatory-hyperplasia assay in SENCAR mice and the UV-induced erythemahyperplasia assay in SKH-1 mice, the most promising mechanisms of anti-initiation and anti-tumor promotion as well as the most effective natural source inhibitors and their delivery means, i.e., topical vs. systemic (dietary); (ii) analysis of the long-term antiinitiation and antitumor promoting effects of the selected, promising natural source inhibitors using the DMBA-initiated, TPA-promoted multistage skin carcinogenesis model in SENCAR mice to better understand their mechanism(s) of action and predict their performance in the following combination studies; (iii) studying the long-term inhibitory effects of the best anti-initiators and anti-tumor promoters identified in Aims 1 and 2, on UV-initiated, TPA-promoted multistage skin carcinogenesis in SKH-1 mice, in order to establish a bridge between the chemically induced and UV-induced mouse skin carcinogenesis data bases; (iv) examining how various combinations of mechanistically different anti-initiators and antitumor promoting agents and also how various combinations of their delivery means, i.e., topical vs. systemic (dietary), inhibit DMBA-initiated, TPA-promoted skin carcinogenesis in SENCAR mice as well as UVinitiated, TPA-promoted skin carcinogenesis in SKH-1 mice, with the view of discovering the most pronounced synergistic effects of the selected natural source inhibitors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMMUNITY-BASED SKIN CANCER PREVENTION RESEARCH Principal Investigator & Institution: Mayer, Joni A.; Professor; Graduate School of Public Hlth; San Diego State University 5250 Campanile Dr San Diego, CA 92182 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The rates of both melanoma and nonmelanoma skin cancers have been increasing in the U.S. Exposure to ultraviolet radiation (UVR) from the sun and artificial sources (such as tanning beds) is a key risk factor. Since 1993, Dr. Mayer has conducted a series of community-based skin cancer prevention studies to assess and modify the sun safety behaviors of both adults and children. Specific high-
Studies 55
risk environments or populations targeted include children enrolled in swimming classes, pharmacists interacting with patients (regarding photosensitizing medications, etc.), zoo visitors, outdoor workers, and operators and patrons of indoor tanning facilities. Dr. Mayer also has a strong track record of mentoring graduate students and junior level faculty, specifically encouraging their involvement in and contributions to cancer prevention and control research. The K05 award would provide Dr. Mayer with release time from teaching and committee assignments, which would enable her to conduct more studies and provide more focused mentoring. A controlled trial evaluating a sun safety intervention for U.S.P.S. letter carriers is in progress. New studies planned for the award period include a multi-level assessment of the predictors of indoor tanning by adolescents, an intervention trial to enhance coping, prevention, and screening behaviors among families of melanoma patients, a trial to assess whether pharmacist advice increases sun safety behaviors of pharmacy customers, and a study to evaluate dissemination strategies for the sun safety program for letter carriers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMPREHENSIVE OUTCOME OF NONMELANOMA SKIN CANCER Principal Investigator & Institution: Chren, Mary-Margaret; Associate Professor; Dermatology; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 28-FEB-2006 Summary: The applicant's long-term career goal is to improve the quality of care for chronic skin conditions. In the last five years, supported by a mentored Clinical Investigator (K08) Award, she has developed a quality-of-life outcomes measure for skin diseases, called Skindex. Her immediate career goal is to compare outcomes of treatments for nonmelanoma skin cancer (NMSC). Her research career development plan centers on a longitudinal cohort study of patients with NMSC. With the proposed support she will acquire enhanced skills by focusing on new research questions in this study sample. ENVIRONMENT. This proposal will be conducted at University of California at San Francisco (UCSF) and its affiliate, the San Francisco Veterans Affairs Medical Center (VAMC). The research will be conducted in the VAMC Survey Research Unit, a laboratory for survey research, chart review, and data management. To address incremental research questions, the applicant will collaborate with UCSF faculty in the Institute for Health and Aging and the Departments of Medicine and Epidemiology and Biostatistics. RESEARCH PROJECT. This proposal focuses on a prospective longitudinal observational study of a cohort of patients newly-diagnosed with NMSC at a private practice and a VAMC dermatology clinic. The goal is to compare treatment outcomes among patients treated in different ways. Principal sources of data are patient survey and medical record review. The primary outcome is skin-related quality of life measured by Skindex; additional analyses will compare tumor recurrence, patient satisfaction, and resource utilization among the treatment groups. The applicant will also learn additional analytic techniques to measure patterns of change in quality of life over time, and will address a new research question about how patients' a priori expectations for care relate to process and outcomes of that care. The proposal is significant because of the prevalence of NMSC and the importance of determining its optimal therapy. In addition, this proposal will provide an intensive novel research focus for the applicant. This opportunity will expand her ability to make a significant contribution to the science of health care quality improvement by determining how
56 Skin Cancer
patients' expectations for care relate to the process and outcomes of their care, thus broadening conventional conceptualizations of health care quality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONFOCAL RAMAN MICROSPECTROMETER FOR CANCER DETECTION Principal Investigator & Institution: Mahadevan-Jasen, Anita; Assistant Professor; Biomedical Engineering; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): In this proposal, the design, assembly and testing of a dual resolution image-guided confocal Raman microspectrometer in a compact instrument is proposed. The proposed system will consist of a handheld probe capable of providing three modes of information. (1) Color video imaging - will provide gross tissue imaging ( about 5mm x 5mm) and thus will guide the selection of interesting areas that require a closer look, (2) Bright-field confocal microscopy - will provide depth resolved morphological mapping from the center of the selected region ( about 300 mu m x 300 mu m) at a cellular level with a single point resolution of 0.75 mu m and (3) Raman microspectroscopy - will provide depth resolved biochemical evaluation of the selected region (same as confocal) with a resolution around 5-10 mu m to be optimized in the R21 phase based on signal to noise. The handheld probe will be coupled to a spectrometer and detector configuration that can compile, process and display all information required for tissue characterization in a compact instrument for clinical use as well research investigation. The instrument proposed here will be optimized for the detection of early skin cancer in a real-time, non-invasive manner as a diagnostic as well as surgical guidance tool.The specific aims of the feasibility phase (R21) of the proposed project are as follows; (1) Design and build a bench-top HIRM probe and instrument,. (2) Characterize Roman signatures of skin tissues in vitro and assess the feasibility of measuring it in vivo (3) Evaluate the parameters necessary to build a miniature HIRM device (4) Design the miniature HIRM probe and system based on the specifications determined in Aim (3). These objectives when achieved will show feasibility of the proposed work, determine the specifications and thus yield a design of a commercially viable, clinical useful handheld image-guided confocal Raman microspectrometer optimized for skin cancer detection.Once designed, the probe and system will be constructed and tested in the R33 phase of the proposal. The specific aims of the development phase of tile proposal are as follows; (1) Build and test the handheld probe and instrument using tissue phantoms and in vitro skin samples, debug system and modify design, (2) Characterize in vivo skin Raman spectra using the bench-top probe on 30 skin cancer patients and 30 normal volunteers, (3) Evaluate the basis for the differences seen in live tissue sections using the confocal Raman microspectrometer. (4) Use the final handheld probe prototype for skin tissue studies in vivo in 30 patients, (5) Develop diagnostic algorithms that distinguish between the various types of malignant and non-malignant skin tissues.The development of the proposed work will have a significant impact on health care by providing the potential for complete disease management with a single compact, sensitive detection tool. With the success of this technique, Raman spectroscopy can be applied to other organ sites such as the prostate and ovary as well as other diseases thus impacting a broader field in medicine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--ANIMAL EXPERIMENTATION Principal Investigator & Institution: Mccormick, Thomas S.; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2006 Summary: Rodents, in particular mice, are extensively used by research projects of several SDRC investigators. An animal core is thus an important component of the SDRC that has been providing expertise and training in the successful completion of animal experiments in a cost effective and highly predictable manner. There is considerable emphasis on skin cancer in the SDRC. There is evident by the fact that 1) five nationally funded projects of this faculty either conduct murine skin tumorigenicity experiments or utilize cutaneous tumors developed on murine skin for biochemical morphological , and molecular biological studies, 2) one of the pilot and feasibility proposed in this renewal application will conduct murine skin tumorigenesis experiments, 3) in the NIH funded training program in Investigative and Molecular Dermatology there are four training tracks, one of which emphasizes skin carcinogenesis. Out of the two current trainees supported by this training grant, one utilizes murine skin tumors and the other conducts animal experiments. The developing emphasis is to utilize chemically mutagenized mice which have clinical phenotypes for dermatitis, susceptibility to UV, cancer and blistering diseases. The additional areas of research in SDRC are a) structural biology and genetics of the skin, and b) immunodermatology. Several investigators conducting research in these areas do animal experimentation. This core has enabled SDRC investigators to conduct animal experimentation more efficiently. The core has four specific functions. The first function is to provide SDRC faculty with a) tissue, in particular tumors, from cutaneous tumorbearing and age- and sex- matched normal mice, and b) homogenate, RNA, DNA, and single cell suspensions, from defined tumors of variously treated mice. The second function is to provide expertise in planning, procurement, and handling of specialized animals for experiments to be conducted by SDRC faculty. Within this objective, the core serves as a resource center in a) providing technical expertise and advise in producing transgenic and knockout mice, and b) conducting experiments on nude mice, e.g. tumor development and their histological verification. The third, which is a newly added function, relates to screening, maintaining and breeding chemically mutagenized mice with clinical phenotypes of skin disease of interest to SDRC investigators. These mice should prove valuable in dissecting complex multi-gene phenotypes. The fourth function of the core is to provide SDRC faculty with biostatistical expertise. For all, experiments involving animal work being conducted and planned for the near future, expertise in murine skin carcinogenesis, biochemistry, genetics, biostatisticians, histopathology and veterinary husbandry and care is needed. Together Core Director, Co-Directors and Consultants represent a team capable of providing expertise in all aspects of animal experimentation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--BIOSTATISTICS Principal Investigator & Institution: Moon, Thomas E.; Assistant and Director; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2001 Summary: The Biostatistics Core Facility for the Program Project is new to this revised application. The Biostatistics Core will provide services and collaboration to all investigators. This will enhance each project, better ensure the most effective design,
58 Skin Cancer
computer data base management and use of statistical methods for integration and analyses of data. The Core will: 1) provide the statistical design of all projects, 2) provide quality assurance of data collection and data entry, 3) develop a coordinated computer data base management system to obtain and integrate data from all projects and cores, 4) provide biostatistical analyses of hypotheses, 5) work collaboratively with investigators to develop and prioritize multivariate, across project hypotheses, and 6) to develop and adapt statistical methods for analyses of multiple biologic markers in aggressive vs. non-aggressive skin cancer research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--CLINICAL AND MOLECULAR EPIDEMIOLOGY Principal Investigator & Institution: Spitz, Margaret R.; Professor and Chair; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2001 Summary: This core will provide comprehensive clinical and molecular epidemiologic support to the relevant components of this Program Project. This core will ascertain and enroll all eligible UTMDACC patients with biopsy-proven non- melanoma skin cancer to form a pool of patients from which cases will be selected for each project according to the specific eligibility criteria. Detailed clinical and epidemiologic data and a blood sample will be collected for all patients. A new molecular component will study p53 and ras mutations in all available tumor specimens. In addition, for Project 3 (Dr. Wei, DNA repair and chromosomal instability in skin cancers) 300 non-cancer controls will be identified; and for Project 5 (Dr. Lippman, Biologic approach to therapy of aggressive skin cancer) data will be collected for the Quality of life component. This core will also be responsible for data quality, management, and retrieval. Data will be maintained in an up-to-date, user friendly, and easily accessible database to facilitate the integration of data from all projects and cores. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CUTANEOUS ONCOLOGY Principal Investigator & Institution: Duvic, Madeleine; Professor and Chief; Dermatology; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 14-AUG-2000; Project End 31-JUL-2005 Summary: This is a mid-career development award application for Madeleine Duvic, Professor of Medicine and Chief of Dermatology at the MD Anderson Cancer Center. It would support a new program in Cutaneous Oncology and enable her to mentor new Assistant Professors, fellows, residents, and medical students in the field. The applicant has an outstanding track record in conducting patient oriented clinical research and is a leader in developing new therapies for the treatment of Cutaneous T Cell Lymphomas (CTCL). There is an unwavering commitment to the conduct of patient oriented research and mentoring at all levels of career development. The award would free the applicant from half of her current clinical duties, allowing her to spend greater than 60 percent of her time on patient oriented translational retinoid research and mentoring activities. A Clinical Research curriculum, an oncology fellows seminar series, and institutional conferences will enhance further career development of the applicant and students. Two translational research projects are proposed using retinoids for cancer. 1] The loss of a novel class II tumor suppressor, Tazarotene Induced Gene 3 (TIG-3), will be investigated in the development and progression of non-melanoma skin cancers. The finding that
Studies 59
TIG-3 is significantly decreased in aggressive versus non-aggressive skin cancer and in basal and squamous carcinomas, compared to paired normal skin will be examined in a larger set of samples and by sequencing cDNAs and by loss of heterozygosity studies. Oral Accutane adjuvant therapy for patients with aggressive tumors may be related to upregulation of TIG-3. 2] Development of molecular markers for Targretin, an experimental RXR selective retinoid, Targretin, will be assessed in the topical and oral treatment of CTCL. Targretin may restore expression of RAR and RXR receptors in epidermis, by altering cytokines and fostering apoptosis of the lymphocytic infiltrates. Patient's skin lesions before and after therapy will be studied using immunohistochemistry and in situ hybridization for retinoid receptors, cytokines, and fas/fas ligand. Genetic basis of large cell progression and gene expression following retinoid therapy will be explored using genomic display and will enhance the training in molecular biology. Understanding the biology of skin cancer and CTCL and the mechanism of novel therapeutic agents should result in the development of better and less toxic therapies for cancer. Young physicians and students who receive advanced training in the proper detection, prevention, and treatment of skin cancers will be a resource and may improve outcomes for patients of the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CUTANEOUS ONCOLOGY PROGRAM Principal Investigator & Institution: Cleaver, James E.; Professor of Dermatology; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001 Summary: (Applicant's Description) Cutaneous malignancies represent the most common type of cancer in the United States. Understanding the biological basis of such cancers, leading to the development of improved therapies, is a major ongoing goal of the Cutaneous Oncology Program, which includes 23 investigators representing 10 departments and three off-site members. The Program includes basic scientists and clinicians with a common interest in understanding the biology of cutaneous neoplasms. One of the major long-term goals of the Cutaneous Oncology Program is to link the clinical activities in malignant melanoma, cutaneous T-cell lymphoma, and nonmelanoma skin cancers with laboratory-based efforts aimed at prevention, improved diagnosis, and treatment of these diseases. The program has access to two large databases of patients with malignant melanoma and cutaneous T-cell lymphoma to assist in the examination of novel molecular determinants of tumor progression. Currently funded research undertaken by program members includes: molecular basis of basal cell nevus syndrome and xeroderma pigmentosum; calcium and keratinocyte differentiation; proteases and progression of squamous cell carcinoma; and multi-step cutaneous carcinogenesis in transgenic mice. Current cancer prevention and control efforts focus on understanding the biology of melanoma in women and improving the diagnostic skills of primary care physicians in the realm of non-melanoma skin cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DFMO PREVENTION STUDY (2B) IN ORGAN TRANSPLANT SUBJECTS Principal Investigator & Institution: Bailey, Howard H.; Assistant Professor of Medicine; Human Oncology; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2006
60 Skin Cancer
Summary: (provided by applicant): Skin cancer is the most common malignancy encountered in the US. While most occurrences of non-melanoma skin cancer can be successfully treated, the growing number of cases and the increased virulence of the malignancy in certain populations make it a significant societal risk. An example of a population at increased risk based on incidence and virulence is organ transplant recipients (OTR), a growing subset of our population due to increased graft survival and numbers of graft recipients. In most series, the incidence of skin cancers in OTR has been > 50% by 20 years post-graft. Initiators and promoters of skin epithelial tumor formation have long been observed to cause increased levels of polyamines and their rate-limiting biosynthetic enzyme ornithine decarboxylase (ODC). Conversely, compounds that decrease ODC activity inhibit skin tumor formation. Difluoromethylornithine (DFMO) is a specific inhibitor of ODC and has been observed to significantly reduce tumor formation secondary to many different initiators and promoters. Past and ongoing chemoprevention studies of DFMO at the UW and other institutions have revealed significant inhibition in ODC activity and polyamine levels in target tissues at relatively nontoxic doses. Due to concerns about chronic immunosuppressants, like cyclosporine, interfering with the ability to adequately measure promoter-induced ODC activity in skin samples and DFMO effects upon graft survival, an initial phase I pilot study of 0.5 and 1.0 g/day of DFMO in OTR was performed. It revealed that 28 days of 0.5 g/day of DFMO significantly inhibited TPA-induced ODC activity and decreased polyamine (putrescine) levels in skin samples of OTR without toxicity.Prior to pursuing a large phase III study of DFMO in OTR, we propose to perform a phase 2b randomized study of 0.5g/day of DFMO versus placebo for one year in OTR at high risk for skin cancer. The primary endpoint would be a greater than 50% reduction in TPA-induced ODC activity in skin samples for one year. Secondary endpoints will be a 50% decrease in skin putrescine and decreased development of skin lesions (actinic keratoses and carcinomas) for one year. Additional parameters include: toxicity assessment including audio grams for ototoxicity, graft status, compliance, and DFMO and immunosuppressant levels.The importance of assessing the biochemical and potential toxic effects of DFMO in OTR, a population at considerable risk of skin cancer, is magnified further by the increased incidence of multiple malignancies in OTR and the importance of ODC induction in many types of tissue carcinogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DNA PHOTOLESION STRUCTURE ACTIVITY RELATIONSHIPS Principal Investigator & Institution: Taylor, John-Stephen A.; Professor; Chemistry; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 01-JUL-1985; Project End 30-APR-2006 Summary: Skin cancer is the most prevalent form of cancer. The key event in uvinduced skin cancer induction is the formation of a mutation that results from DNA synthesis past a DNA photo product by a DNA pommies. The overall aim of this proposal is to understand how and why some polymers are able to synthesize past DNA photo products while others are not, and the mechanisms by which polymerase bypass DNA photo products while others and select the nucleotide that are inserted opposite them. We plan to approach this problem by a combined chemical, physical, enzymatic, and biological approach, which relies our ability to synthesize photo productcontaining DNA substrates for detailed study. Specifically, we propose to develop new routes for the synthesis of photo product and analogs which can test hypotheses regarding nucleotide insertion selectivity opposite DNA photo products. The structure, H-bonding, proton exchange rates, dynamics, and thermodynamics of photoduct-
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containing duplexes will be studied to further understand the molecular basis for nucleotide insertion preferences opposite DNA photo products by polymerase. To better understand the difference between replicative and DNA damage bypass polymerase, we will carry out a detailed kinetic and physical analysis of the individual steps in the bypass of DNA photo products. We will investigate the role of sequence context on bypass rates and nucleotide insertion selectivity opposite DNA photo products by DNA polymerase, and the extent to which polymerase can switch a primer from one temple late to another at replication fork. We will investigate the molecular basis for the A-rule in bypass of DNA photo products, and the effect of sequence context on bypass rate and nucleotide insertion selectivity. A number of chemical and physical agents will be investigating as probes for how DNA polymerase bind to native and photo damaged template primers at various steps in the elongation process. Replication of SV40 vectors containing photo products and analogs will also be studied in normal and XPV human cell extracts as a function of leading and lagging strand synthesis, and sequence context. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DNA REPAIR AND CANCER PRONE HEREDITARY HUMAN DISEASE Principal Investigator & Institution: Friedberg, Errol C.; Professor and Chair; Pathology; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001; Project Start 01-FEB-1987; Project End 31-JAN-2003 Summary: The long-term objectives of this proposal are to investigate the relationship of defective repair of DNA damage to cancer in humans. To this end mutational inactivation of various DNA repair genes in mice by targeted gene replacement is being used as an experimental strategy. A mouse strain has been generated which carries homozygous deletions in the nucleotide excision repair (NER) gene XPC. This strain is exceptionally prone to ultraviolet (UV) radiation-induced skin cancer. Experiments are in progress to determine predisposition to liver cancer associated with exposure to the liver carcinogen 2-acetylaminofluorene, the repair of which requires the process of NER in mammals. XPC-1- mice that are additionally heterozygously or homozygously defective in the p53 tumor suppresser gene exhibit an even greater predisposition of skin cancer. Studies are proposed to investigate the mechanism of this synergistic interaction, in particular whether abrogation of the G1->S checkpoint function or of the apoptotic function of the p53 gene (or both), mediates this effect. Dr. Friedberg will generate a mouse strain by targeted gene replacement that is homozygous defective in the HAP1 gene which encodes the major apurinic/apyrimidinic (AP) endonuclease required for the process of base excision repair (BER) in mice. Such a mutant mouse is expected to be defective in the repair of various types of spontaneous base damage in DNA, particularly that generated by oxidative metabolism. Crosses will be made between the XPC-1- (NER-defective) mouse, the HAP1-/- (BER-defective) mouse and mice defective in the mismatch repair defective mouse MSH2, in order to investigate the role of all three known excision repair pathways in both spontaneous and environmental carcinogen-induced cancer in mammals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DNA REPAIR AND CHROMOSOME INSTABILITY IN SKIN CANCERS Principal Investigator & Institution: Wei, Qingyi; Professor; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030
62 Skin Cancer
Timing: Fiscal Year 2001; Project Start 06-AUG-2001; Project End 31-MAR-2003 Summary: Basal cell and squamous cell carcinomas (BCC and SCC) commonly occur on exposed sites such as the head and neck and are usually due to chronic exposure to solar ultraviolet radiations (UVR). The role of host susceptibility to UVR carcinogenesis is not well defined at either the molecular or cytogenetic level. We propose to conduct a casecontrol study to evaluate the association between genetic susceptibility to UVR (defined as decreased DNA repair capacity or increased mutagen sensitivity) and the development and progression of skin carcinomas. The DNA repair capacity will be measured by host-cell reactivation assay with UV- irradiated plasmids. Mutagen sensitivity will be measured by UVR induced chromosomal breaks and the frequency of break sites on chromosomes. We will use peripheral blood lymphocytes from 300 untreated cases (150 BCC and 150 SCC) and 300 controls to perform these assays. The specific aims of this proposal are: (1) to examine the association between DNA repair capacity and the development of skin carcinomas, (2) to examine the association between mutagen sensitivity and athe development of skin carcinomas, and (3). To examine the association between the frequency of break sites on chromosomes and the development and progression of skin carcinomas, and (4) to evaluate the association of DNA repair capacity with mutagen sensitivity, frequency of chromosomal break sites, gene mutations, and epidemiologic and clinical variables such as sunlight exposure history, clinical stage of disease, and treatment outcomes. We will investigate the relationship between these two genetic susceptibility markers and the development of skin carcinomas in relation to phenotypic characters, family history, sunlight and other carcinogenic exposures, the frequency of mutations in ras oncogenes and p53 tumor suppressor genes clinical stage and progression of tumors (to be collected by Core B; Drs. Margaret Spitz, Randal Weber, and Honnavara Ananthaswamy) and treatment outcomes (to be measured by Drs. Scott Lippman and Reuben Lotan) from the same subjects. This study will provide information regarding the utility of these markers of genetic susceptibility in identifying individuals at high risk of developing skin carcinomas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DNA REPAIR, GENETIC VARIATION AND SKIN CANCER Principal Investigator & Institution: Hunter, David J.; Director; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant)We propose to prospectively assess the association of low-penetrance polymorphisms and haplotypes in candidate DNA repair genes to the risk for melanoma and non-melanocytic skin cancers including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in the Nurses' Health Study. We hypothesize that candidate polymorphisms and haplotypes in three important DNA repair genes (XPD in nucleotide excision repair; XRCC1 in base excision repair; XRCC3 in homologous recombination repair) are associated with higher risk of skin cancer. We will further examine whether the candidate polymorphisms modify the association between the sunlight exposure and the risk of skin cancer. After blood collection in 1989-90 up to 1998, we have accrued 743 incident cases of skin cancers (177 melanoma, 283 SCC, and 283 BCC which were randomly selected from diagnosed BCC cases); each case will be matched by age and race to a control in the nested case-control study. We will have >90% power to detect relative risks of 1.5 or greater for the main effects of most of the genotypes of interest. We will also have substantial power to detect interactions between these genotypes and lifetime sunlight exposure. This study will be
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among the first studies of the association of polymorphisms in candidate DNA repair genes with skin cancer, which assess potential interactions between genotype and sunlight exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DO NKT CELLS MEDIATE UV INDUCED IMMUNE SUPPRESSION? Principal Investigator & Institution: Ullrich, Stephen E.; Professor; Immunology; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (provided by applicant): - In addition to being a complete carcinogen, exposure to ultraviolet (UV) radiation is immunosuppressive. Studies with both experimental animals and biopsy proven skin cancer patients have indicated that the immune suppression induced by UV radiation is a major risk factor for skin cancer development. Exposing mice to subcarcinogenic doses of UV suppresses their immune response and allows for the outgrowth of UV-induced skin cancers. This immune suppression can be transferred to normal recipients by adoptive transfer of splenic CD3+, CD4+, CD8- suppressor T cells (UV-Ts), cells that are also responsible for controlling the induction of the primary tumor in the UV-irradiated host. One glaring gap in our knowledge of the mechanism(s) by which UV exposure suppresses tumor immunity is the incomplete understanding of the exact identity and function of UV-Ts. Previous studies from this laboratory indicate that one mechanism by which UV-Ts down-regulate immunity is by interleukin (IL)-2 secretion. According to current immunological literature, only two T cell subsets readily secrete IL-4, T heIper-2 cells, and natural killer T (NKT) cells. Because of unique surface markers on NKT cells, it is possible to separate T helper-2 cells from NKT cells. Our preliminary findings indicate that a highly purified population of NK1 cells can transfer suppression of tumor immunity from UV-irradiated mice to normal recipients. The focus of this grant proposal is to test the hypothesis that UV-Ts are NKT cells. The specific alms of this grant are designed to answer the following questions: 1) Are UV-Ts NKT cells? 2) How do NKT cells suppress tumor rejection? 3) Is the activation of UV-induced NKT cells CD1 restricted? 4) How does the altered cytokine environment found in UV-irradiated mice affect the induction/activation of NKT cells? 5) Is it possible to clone NKT cells with suppressive activity from the lymphoid organs of UV-irradiated mice? The longterm goal of this research is to determine how UV exposure induces systemic immune suppression and permits the outgrowth of skin cancer. Because there is a link between the ability of UV exposure to suppress immunity and induce skin cancer, it is critically important to understand how these immune regulatory cells function to suppress immunity and promote cancer development. A better understanding of the mechanisms involved in UV-induced immune suppression may help with the design of rational approaches to block immune suppression, thereby reducing one of the major risk factors for skin cancer induction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECT OF TEA ON FORMATION AND GROWTH OF SKIN TUMORS Principal Investigator & Institution: Conney, Allan H.; Chairman; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, NJ 08901 Timing: Fiscal Year 2001; Project Start 17-SEP-2001; Project End 31-AUG-2006
64 Skin Cancer
Summary: (provided by applicant): In an earlier cancer chemoprevention study, we exposed SKH-1 mice to ultraviolet light (UV) twice a week for 22 weeks, and UV administration was stopped. The mice were tumor-free but they had hyperplasia and a high risk developing skin tumors during the next several months in the absence of further UV administration ("high risk mice"). This is a useful model that may be comparable to humans previously exposed to moderate/high levels of sunlight who have a high risk of developing skin cancer later in life even in the absence of continued heavy sunlight exposure. We plan to: 1. Compare the effects of orally administered green tea, decaffeinated green tea, caffeine and (-)-epigallocatechin gallate (EGCG) on the formation and growth of nonmalignant and malignant skin tumors in "high risk mice." Nontumorous areas of the skin and epidermal tumors from these mice will be used for mechanism studies described in "2" and "3" below. 2. Determine molecular mechanisms for the effects of orally administered green tea, decaffeinated green tea, caffeine, and EGCG on the formation and growth of nonmalignant and malignant skin tumors in "high risk mice. " We will determine the effects of these treatments on proliferation and apoptosis and on key molecular signal transduction markers of proliferation and apoptosis in normal epidermis, hyperplastic epidermis, nonmalignant tumors and malignant tumors. 3. Determine the effects of oral administration of green tea, decaffeinated green tea, caffeine and EGCG in "high risk mice? on fat levels and evaluate the relationship between decreased fat levels and inhibition of carcinogenesis. Possible relationships between lipid levels, number of tumors per mouse and tumor size per mouse in individual mice will be determined. 4. Determine the effects of short-term and long-term topical applications of EGCG, caffeine and combinations of EGCG and caffeine to "high risk mice" on biomarkers of proliferation and apoptosis and on subcutaneous fat levels. Effects on the formation and growth of nonmalignant and malignant tumors will also be evaluated. We will compare the results of topical application studies with those from experiments with oral administration to determine possible mechanistic differences between the two modes of administration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPIDEMIOLOGY OF ARSENIC Principal Investigator & Institution: Karagas, Margaret R.; Professor; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, NH 03755 Timing: Fiscal Year 2001 Summary: Overall objectives of the proposed study are to quantify carcinogenesis risks due to arsenic exposure at levels commonly found in the US. This research project shares the goals of the program of the program project of furthering our understanding of the environmental and health effects of arsenic has been identified as a potent skin carcinogen in highly exposed in rural regions of the northeastern US. Arsenic has been identified as a potent skin carcinogen in highly exposed human populations, but it is uncertain whether these effects occur at low levels. We propose to extend our epidemiological case-control study of bladder and skin of bladder and skin cancers in a US population: (1) to further resolve the dose-response relationship between low to moderate levels of arsenic exposure and risk of bladder cancer, (2) to test the hypothesis that arsenic is related specifically to intraepidermal carcinomas (including Bowen's disease) and multiple concomitant basal cell carcinomas (BCC) of the skin, and (3) to identify subgroups of individuals who may be at high risk of arsenic-associated cancers due to co-carcinogen exposure (e.g., low selenium). We will expand our investigations of individual biomarkers of arsenic exposure by testing the reliability of existing measures (drinking water, urine, and toenails) and exploring new molecular-genetic
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markers (i.e., based on cDNA arrays). New Hampshire is ideally suited to study the effects of low-dose arsenic exposure since it is one of the few regions of the country with a population-based surveillance system for non- melanoma skin cancer and over 20% of the private wells in the region contain levels of arsenic suspected of being carcinogenic. New Hampshire has unusually high bladder cancer mortality rates which are as yet unexplained, and there is accumulating evidence that these malignancies may result from arsenic ingestion. Thus, our study provides a unique opportunity to obtain results directly applicable to the US population and to help identify those at greater risk for arsenic-induced malignancies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPIDEMIOLOGY OF HPV AND P53 MUTATIONS IN NM SKIN CANCER Principal Investigator & Institution: Kiviat, Nancy B.; Director of Pathology; Pathology; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Although little mortality is associated with squamous cell skin cancer (SCSC), these cancers constitute a major public health problem due to the high costs associated with treatment. The relationship between ultraviolet radiation (UVR) exposure and development of SCSC is well established, however, the molecular biology underlying this association is unclear. We hypothesize that many of these tumors result from acquisition of UVR-induced mutations in genes that normally maintain genetic stability, and in particular mutations in the p53 gene, along with infection with certain cutaneous human papillomaviruses (HPVs). Confirming this hypothesis has significant public health implications, since, if true, HPV type-specific vaccines (similar to those now being tested for prevention of cervical cancer) could be developed and specific p53 mutations (or associated proteins) could serve as a target for the design of additional preventive therapeutics. Animal and cell culture models support a role for specific p53 mutations acquired with the formation of UVR-induced dipyrimidine dimers, however, systematic, DNA sequence and cloning based examination of tissue from incident SCSC and nonlesional control tissues has yet to be undertaken in humans. The limited available data suggest that p53 mutations might be present in over 90 percent of SCSC tissue and in up to 50 percent of sun exposed non-cancerous skin cells. Similarly, small case series in immunocompetent patients have shown that cutaneous HPV DNAs are present in over 90 percent of SCSC lesions and in up to 50 percent of control tissues. Interestingly, our recent studies show that the upstream regulatory region (URR) of specific cutaneous HP Vs is activated by UVR exposure via p53 proteins binding to a p53 consensus sequence in the URR of some cutaneous HPVs. Further, different p53 proteins appear to differ in their ability to activate HPV. These findings, along with the fact that cutaneous HPV E6/E7 proteins are known to induce proliferation and clonal expansion of infected cells, lead us to propose the following. We hypothesize that UVR exposure of epithelial cells results in acquisition of pyrimidine dimers with selection of mutations in the p53 gene, as well as selection of mutations in those genes that normally maintain genetic stability. Such cells, which have acquired a "mutator phenotype," have the potential both to accumulate the many mutations characteristic of, and necessary for, progression to cancer and the ability to abrogate apoptosis. However, the ability of these abnormal cells to progress to malignancy most likely requires increased proliferation and clonal expansion. We hypothesize that if such abnormal cells are infected with a cutaneous HPV type that is activated upon UVR exposure, that such exposure leads to HPV dependent proliferation
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and clonal expansion. Subsequent exposure of this population of cells to UVR, with successive rounds of mutation, selection and HPV-dependent clonal expansion, could lead to accumulation of those mutations associated with development of a malignant phenotype. We propose to examine this hypothesis by undertaking a case-control study and a laboratory based study designed to provide confirmation of the biologic relevance of our clinical findings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EVALUATION OF TAILORED SKIN CANCER PREVENTION STRATEGIES 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-1998; Project End 31-JUL-2004 Summary: (adapted from investigator's abstract): Skin cancer is among the most common cancers in the United States, and it is also one of the most preventable and survivable if detected early. Risk factors for skin cancer include excess sun exposure, family history, personal history of skin cancer or precancerous lesions, and physical characteristics. Novel approaches for improving preventive and early detection behaviors need to be developed and evaluated among high-need and high risk groups. The aims of this study are to: 1) Evaluate the impact of a mailed, tailored intervention including risk feedback and self-monitoring, on the skin cancer prevention and skin self-examination behaviors of high-risk and moderate-risk adults; and 2) Evaluate the impact of a mailed, tailored, family-based intervention including risk feedback, UV radiation exposure self-monitoring, and interactive parent-child activities, on skin cancer prevention and parental skin examination behaviors for children in grades one through three. Ancillary aims are to: 1) evaluate the process and impact of the interventions on diverse ethnic groups in two regions; 2) advance the development of valid, reliable, and precise behavioral measures; and 3) refine skin cancer risk assessment methodologies. The study design involves two randomized controlled trials, one with adults and the other with children and parents. Intervention materials will be mailed. The trials will have parallel methodologies and will compare tailored, theorybased intervention materials and UV monitoring aids with a control condition using standard information on sun safety and early detection. The results of this research will increase our knowledge of effective, low-cost, cancer control strategies that can be implemented in public health, managed care, school, and recreation settings. The findings will advance the science of risk assessment and of methods for measuring skin cancer prevention practices in adults and families. The project will also make significant contributions to our understanding of the responses of geographically and ethnically diverse groups to skin cancer preventive interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE THERAPY FOR HUMAN MALIGNANT MELANOMA Principal Investigator & Institution: Grimm, Elizabeth A.; Professor and Section Head; Introgen Therapeutics, Inc. 2250 Holcombe Blvd Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 02-JUL-2001; Project End 30-JUN-2003 Summary: (Applicant's Description) Melanoma is the most malignant of skin cancers. In the USA, the incidence of melanoma is increasing more rapidly than any other cancer. Melanoma is the most frequently occurring cancer in women from the ages of 25-30, and has recently replaced leukemia as responsible for the most lost work hours in the
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United States. Currently there is no approved therapy that achieves more that a 20% response rate. Therefore, better therapies for malignant melanoma are urgently needed. Introgen Therapeutics is developing a novel anti-tumor gene therapeutic, Ad-mda7, and has demonstrated it's anti-tumor potential against breast and lung cancer cell lines. Here, we propose to perform proof-of-principle experiments to evaluate the efficacy of Ad-mda7 in melanoma. Growth inhibition studies will be performed using human melanoma cell lines in vitro and, if successful, will progress to evaluate Ad-mda7 in vivo using human melanoma xenografts. If these first aims are successful, we will test Ad-mda7 alone and in combination with conventional chemotherapeutic agents using metastatic tumor models. At the end of this Phase I STTR, we plan to have gathered the necessary efficacy data to proceed to safety studies and IND filing in a Phase II STTR, based on clinical trial testing of Ad-mda7. PROPOSED COMMERCIAL APPLICATION: Ad-mda7 is a gene therapy drug to be tested as a novel therapeutic for the treatment of malignant melanoma. Malignant melanoma is a dire skin cancer with few available treatment options. The incidence of melanoma and malignant melanoma is increasing. Approximately 41,000 people are predicted to diagnosed with melanoma this year, with more than 7,000 deaths resulting from this disease. The studies outlined here will guide the preclinical development of Ad-mda7 for melanoma. Subsequent Phase II studies will evaluate the therapeutic potential of Ad-mda7 in clinical trials with the goal of submission of a BLA to the FDA and subsequent marketing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC ANALYSIS OF CHEMICALLY INDUCED LYMPHOMAS IN MICE Principal Investigator & Institution: Conti, Claudio J, Dvm.; Biologist & Professor; Carcinogenesis; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 23-MAY-2001; Project End 31-MAR-2005 Summary: (provided by applicant): The outbred SENCAR stock of mice has been a useful model for dissecting out the multistage nature of cancer development as well as the critical mechanisms involved in skin tumorigenesis. More recently several inbred strains derived from the SENCAR stock have been developed. These strains display different sensitivities to two-stage carcinogenesis and, in particular, some of them show a dissociation between the susceptibility to papilloma development and their malignant conversion into Squamous Cell Carcinomas (SCC). Interestingly we have recently shown that the treatment of young SENCARB/Pt mice with N-methyl-N-nitrosourea (MNU) results in the induction of a high incidence (> 90 percent) of thymic lymphomas occurring between 4 and 6 months after MNU injection. In contrast SSIN mice were not susceptible to MNU induced thymic lymphomas supporting the idea that the differential susceptibility to chemical carcinogenesis between SSIN and SENCARB/Pt is not restricted to the skin model and therefore, these strains constitute a powerful tool for the mechanistic studies of the underlying genetic basis of resistance and susceptibility to chemical carcinogenesis. Specific Aim 1: To establish a genetic mode or the susceptibility to chemically induced thymic lymphomas using SSIN (resistant) and SENCARB/Pt (susceptible) strains. The long-term objective of this project is to identify the putative resistance/susceptibility gene/s that play a role in the differential behavior against chemical carcinogenesis in these two SENCAR-derived inbred strains and investigate their possible mechanisms of action. Using a backcross we have previously identified a region on mouse chromosome 14 containing a putative susceptibility gene for skin tumor progression. We are now proposing to use the lymphoma model to investigate
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whether lymphoma susceptibility is controlled by the same locus and follows the same genetic models than that observed in the skin model. Specific Aim 2: To identify the gene/s involved in the differential susceptibility to MNU carcinogenesis by positional cloning. We will develop a high-resolution linkage map and a physical map of the region/s harboring gene/s involved in MNU-induced thymic lymphoma susceptibility using intercross mice between the wild derived MBT/Pas strain and SENCARB/Pt. We will continue with approaches to isolate at least the more relevant gene by positional cloning, and positional candidate routes. Specific Aim 3: To investigate the extent of the susceptibility of SENCARB/Pt to environmental carcinogens. So far, we have shown differences in susceptibility in lymphomas and progression of skin cancer. The purpose of this specific aim is to investigate if SENCARB/Pt mice have also a higher susceptibility to chemically induced mammary carcinomas and UV induced skin carcinomas. Specific Aim 4: To investigate whether genomic instability plays a major role in the phenotypic differences between SSIN and SENCARB/Pt strains against chemical carcinogenesis. We have the hypothesis that the differences in susceptibility to chemical carcinogenesis between these strains are related to the different levels of genomic instability displayed. Using a new PCP technique we will be able to evaluate the degree of genomic instability and if this hypothesis is substantiated we will investigate probable mechanisms involved in this phenomena. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC VARIATION IN DNA REPAIR AND RISK FOR LYMPHOMA Principal Investigator & Institution: Adami, Hans-Olov H.; Karolinska Institute Tomtebodavagen 11F Stockholm, Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Rising incidence trends of non-Hodgkin's lymphoma (NHL) have been observed in the Western world during more than four decades; still, the underlying causes for the vast majority of all cases of NHL, and consequently, for the increasing temporal trends, remain unestablished. Different lines of evidence indicate an association between ultraviolet radiation (UVR) exposure and risk of NHL, including increased occurrence of lymphomas in skin cancer patients and vice versa. Average levels of UVR exposure and skin cancer incidence are also known to increase in many populations. DNA repair genotypes relate to the capacity to repair UVR-damaged DNA and to skin cancer susceptibility. We propose to investigate if polymorphisms in genes involved in repair of UVR-damaged DNA are associated also with susceptibility for NHL. We intend to use blood samples collected in a large NIHsupported population-based case-control study, including in total 3 000 NHL cases and 2 800 controls in Sweden and Denmark. Specifically, we plan to analyze if 21 single nucleotide polymorphisms and haplotypes in genes involved mainly in the nucleotide excision repair pathway, are associated with NHL in a subset of 500 cases and 500 controls selected at random. In the case-control study, questionnaire data on UVR exposure has also been collected; therefore, the proposed study will, in addition, give us the unique opportunity to investigate both genetic and environmental aspects of UV exposure in the same individuals in analyses of gene-environment interaction. To our knowledge, genetic variance related to repair of DNA damage, induced for example by UVR, has not been investigated before in association with NHL. Polymorphisms associated with DNA repair capacity may be important markers of the individual's susceptibility to develop NHL, and may also serve as markers of modification of a carcinogenic exposure effects, UVR, for example. In light of the intriguing associations
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between lymphomas and skin cancer on one hand, and between UVR exposure, DNA repair genotype, and skin cancer on the other, we believe that testing this novel hypothesis might add important biological information to the enigma of NHL etiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GREEN KERATINOCYTES
TEA
POLYPHENOL
CHEMOPREVENTION
IN
Principal Investigator & Institution: Eckert, Richard L.; Professor; Physiology and Biophysics; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2002; Project Start 10-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Cancer begins with a normal cell that, due to persistent environmental insult, is transformed, via a series of progressively more insidious steps, into a cancer cell. A major goal of chemopreventive therapy is to alter the normal cell response to the environmental agent with the goal of inhibiting disease. (-)-Epigallocatechin-3-gallate (EGCG) is an important bioactive antioxidant, derived from tea, that possesses remarkable cancer chemopreventive properties. Most studies with this agent are performed with cancer cells, however, it is equally important to understand whether these chemopreventive effects extend to normal pre-cancerous cells. Our initial studies show that EGCG increases normal keratinocyte differentiation, as assessed by EGCG-dependent up-regulation of involucrin (hINV) promoter activity, and increased cornified envelope formation. The hINV gene provides an ideal tool for studying the mechanism whereby EGCG regulates keratinocyte differentiation. The EGCG-associated response is mediated via an AP1 site within the hINV promoter and appears to involve a MAPK signaling cascade. Based on these results, we hypothesize that EGCG acts to prevent cancer development by promoting keratinocyte differentiation via an AP1 factor-dependent mechanism. The experiments outlined in this proposal are designed to shed light on the mechanism whereby EGCG stimulates keratinocyte differentiation. The ultimate goal is to better understand how green tea prevents skin cancer. Our first goal is to characterize the mechanisms whereby EGCG promotes an AP1-factor-dependent increase in hINV gene expression. To achieve this goal, we will measure EGCG effects on AP1 factor levels, AP1 factor/DNA interaction at the AP1 site, and AP1 factor phosphorylation state. Our second goal is to determine whether EGCG influences the p38 MAPK cascade that regulates hINV gene expression. This will be accomplished by examining the ability of dominant-negative kinases and pharmacologic inhibitors to modulate the EGCG-dependent regulation. Our third major goal is to evaluate whether EGCG can counter a pro-carcinogenic challenge - treatment with UVB. Fourth, it is important to affirm that EGCG has pro-differentiation promoting properties in epidermis. We hypothesize that EGCG will enhance keratinocyte differentiation in vivo. We will test this hypothesis using a unique series of transgenic mice that encode varying length of the hINV promoter. These studies will make it possible to study the mechanism of EGCG-dependent in vivo regulation. The central goal of this proposal is to gain new information regarding the mechanism of EGCG action. It is hoped that these studies lead to the design of new strategies for enhancing the effectiveness of these agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HAND-HELD CONFOCAL LINE-SCANNER FOR INTRASURGICAL USE Principal Investigator & Institution: Eastman, Jay M.; Lucid, Inc. 50 Methodist Hill Dr Rochester, NY 14623
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Timing: Fiscal Year 2003; Project Start 14-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Design of a laboratory prototype, product development and clinical testing of a real-time hand-held confocal line-scanner is proposed for imaging-guided microsurgery applications. Line scanning offers resolution, contrast and field of view that are required for intrasurgical imaging. In the Phase I feasibility project, the laboratory prototype successfully demonstrated imaging of nuclear and cellular detail in human epidermis in vivo with 5-10 microns resolution. In Phase II, the goals are to quantitatively characterize optical performance within living human skin, package the prototype into a hand-held confocal scanner product, and test the scanner for imaging basal cell cancers on patients during Mohs surgery. Vis-a-vis the current method based on frozen pathology, real-time in situ confocal imaging may save both Mohs surgeon and patient several hours in the operating room. The hand-held linescanning confocal microscope will have everything that surgeons and patients want: simple and robust design, inexpensive ($10K-20K), user-friendly package, controls and interface, and standard detection and display systems. The first application is for skin cancer but other tissues will be subsequently imaged as well. The intended users are surgeons, and the potential benefits to the patient are: painless, fast, less expensive and therefore significantly improved healthcare. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HAWTHORNE CONFERENCE ON OFFICE-BASED SURGERY Principal Investigator & Institution: Feldman, Steven R.; Professor; Dermatology; Wake Forest University Health Sciences Winston-Salem, NC 27157 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2002 Summary: (provided by applicant): This is an application to support the Hawthorne Conference on Office-Based Surgery to be held November 16-17, 2001 entitled " Benefits and Risks of Office-Based Surgery: Special Emphasis on Dermatologic Procedures" at the Hawthorne Inn & Conference Center, Winston-Salem, North Carolina. It is the first national multidisciplinary conference focusing on critical issues relevant to the safety and cost-effectiveness of office-based surgery in general and dermatologic procedures in particular. This application is requesting partial support for this endeavor that will focus on the scientific understanding of the benefits and risks of office-based surgery. There has been an acute need to address in a scientific manner the information that is available on office-based surgery. This is essential, as understanding the previously unrecognized or under-emphasized benefits and risks of office-based surgery will have important clinical and research implications regarding the patient safety and cost-effectiveness of surgical care at the office-based setting. The Hawthorne Conference is designed to review and integrate the scientific knowledge concerning the benefits, risks and costs of surgery, particularly skin surgery, performed at the office-based setting. It consists of three sessions that focus on: effectiveness of office-based surgery, safety and risks of office-based surgery, and cost benefits of office-based surgery. The specific topics will include the risks of office-based anesthesia, evidence on appropriate anesthesia monitoring for the office, documentation of deaths at office-based dermatologoic surgery procedures, hospital deaths from dermatologic procedures, cost and effectiveness of skin cancer removal in the office-based and hospital-based settings. Key participants will include individuals with a record of expertise in publication in health services research as well as the different clinical physician specialties most related to dermatologic surgery including dermatologists, surgeons, and anesthesiologists. The major conclusion of the conference will be to identify those areas that require additional
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research as a basis for improving patient safety, quality of care, and physician accountability during the office-based surgery in a cost effective manner Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIGH-FREQUENCY IMAGING:PHOTOACOUSTIC
MULTI-MODALITY
Principal Investigator & Institution: Wang, Lihong; Professor and Director; Biomedical Engineering; Texas Engineering Experiment Station 308 Wisenbaker Engrng Res Center College Station, TX 77843 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): The long-term objective of the proposed research is to develop a novel diagnostic tool for microscopic imaging of superficial lesions that can be accessed either non-invasively or minimally invasively. The proposed technique, high frequency photoacoustic tomography (PAT), can image intact biological tissues at the microscopic scale in vivo based on optical contrast. Optical contrast is sensitive to the molecular conformation of biological tissues and is related to physiological states such as the oxygenation of hemoglobin. Applications include the diagnostics of, for example, skin cancer, cervical cancer, esophageal lesions, and vulnerable atherosclerotic plaques. PAT can also potentially be used to spatially resolve molecular beacons for high-resolution and high-sensitivity imaging. The proposed PAT combines the contrast advantage of optical imaging with the resolution advantage of ultrasound imaging. The proposed technology does not depend on ballistic or backscattered light as optical coherence tomography (OCT) does. Any light, including both singly and multiply scattered photons, contributes to the imaging signal; as a result, the imaging depth in PAT is excellent. The resolution is diffraction limited by the high-frequency photoacoustic waves rather than the optical diffusion; consequently, the resolution of PAT is excellent. Furthermore, PAT is free of the speckle artifacts present in OCT and pulse-echo ultrasonography, two analogous technologies. PAT images of unprecedented high quality have been obtained by the Texas A&M groups. In the proposed research, PAT and high-frequency ultrasound imaging will be performed on the same cross sections of tissue. This multi-modality approach will allow us to obtain both optical contrast and acoustic contrast, and the dual contrasts are expected to provide greater diagnostic value. A unique strength of the proposed research is the multi-disciplinary team and the support of the NIH Resource on Medical Ultrasonic Transducer Technology, which has been funded to pursue state-of-the-art research in the development of high-frequency ultrasound transducers/arrays. The specific aims of the proposed research, in which the animal experiments will have dual foci--the imaging of skin cancers (animal model 1) and the imaging of atherosclerotic plaques (animal model 2), are as follows: Aim 1. Develop a 30-MHz PAT system to image biological tissues with both high optical contrast and high resolution in real-time acquisition. Aim 2. Characterize the imaging capability of the proposed hand-held probe by imaging skin cancers in vivo in a mouse model (animal model 1). Aim 3. Characterize the imaging capability of the proposed hand-held probe by imaging atherosclerotic plaques ex vivo in a rabbit model (animal model 2). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIGHLY DIFFERENTIATED TISSUE CULTURE MODELS OF MELANOMA Principal Investigator & Institution: Klausner, Mitchell; Mattek Corporation 200 Homer Ave Ashland, MA 01721
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Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-MAR-2003 Summary: (provided by applicant): With the exception of lung cancer in women, the incidence of cutaneous melanoma (CM) is increasing faster than any other cancer. Current estimates are that one of every 75 individuals in the US will contract CM during his or her lifetime. The various stages of melanoma have been well described, however, to devise improved treatments allowing patients to lead longer and more productive lives, a better understanding of progression of CM is needed. The purpose of this proposal is to produce highly differentiated, tissue culture models of the various stages of CM progression. During Phase I, cell lines from the various disease states of CM will be expanded in monolayer culture and characterized. Using a serum free culture system, these cells will be incorporated into an organotypic, full thickness skin model to produce tissue reconstructs which parallel the various stages of CM in vivo. The tissues will be characterized in terms of morphology, tumor progression, and adhesion receptors. Finally, reproducibility of the tissue models will be investigated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNODERMATOLOGICAL THERAPY OF SKIN CANCER Principal Investigator & Institution: Elmets, Craig A.; Professor and Chair; Dermatology; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2001; Project Start 06-JAN-1999; Project End 31-DEC-2003 Summary: Non-melanoma (basal cell and cutaneous squamous cell carcinomas) skin cancer and melanoma are common human malignancies whose growth is controlled at least in part by T-lymphocyte mediate immune responses. There is great interest in developing new modalities which will enhance and exploit this host defense mechanism for therapeutic benefit. We have observed that cutaneous squamous cell carcinomas and melanomas exhibit a profound reduction in tumor growth when treated with the bacterial super- antigen Staphylococcal enterotoxin B (SEB). The response is immunologic in nature and is highly specific for malignant tissue, both in vivo and in vitro. SEB may thus have great potential as a immunodermatologic therapy for skin cancer. In this proposal, we plan to investigate the hypothesis that the bacterial superantigen SEB causes selective destruction of non- melanoma and melanoma skin cancers by serving as a ligand between the tumor cell and cytotoxic T-lymphocytes. We will more fully assess the immunodermatologic potential of SEB as a therapy for skin cancer by studying the range of cutaneous tumors responsive to SEB immunodermatologic therapy. We will also assess the efficacy of mutants SEB as therapeutic agents in skin cancer in order to identify those regions of the molecule most important at causing regression of skin cancers. Studies will be performed to evaluate whether inhibition of tumor cell growth by SEB and T-cells is cytotoxic in nature. Experiments will be conducted to identify the molecule on cutaneous squamous cell carcinomas to which SEB binds that allows it to inhibit the growth of cutaneous tumors. We will be particularly interested in determining whether SEB binding to major histocompatibility complex class I and class II molecules plays a role in the response. Because SEB limits the growth of malignant cells, but has little effect on keratinocytes from which these tumors are derived, we will investigate whether this is due to differential binding on SEB to tumor cells versus normal keratinocytes, differences in the expression of the adhesion molecule ICAM-1 on these two cell types, or to differences in the Fas pathway in normal versus malignant keratinocytes. Finally, experiments will be performed to precisely define the characteristics of the T-cell most effective at causing SEB-induced regression of cutaneous tumors. The ultimate goal of this proposal is to generate new
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knowledge that can be used to develop new and better strategies for the control of nonmelanoma and melanoma skin cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNOLOGY AND IMMUNOTHERAPY Principal Investigator & Institution: Bellgrau, Donald L.; Professor and Program Leader; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001; Project Start 01-MAR-1988; Project End 31-JAN-2006 Summary: (Applicant's Description) The overall goal of the Program in Immunology and Immunotherapy is to understand the basic elements of immunity and the mechanisms by which cancer cells evade the immune system so that new intervention strategies can be developed to reduce the cancer burden. This is accomplished programmatically by fostering collaborations and encouraging a broad range of investigations into the connections between immunity and cancer. The University of Colorado Cancer Center leadership reorganized the structure of the Cancer Center in 1998 and 1999 in order to better promote translational research and collaborations, and to strengthen the cancer focus. The old Melanoma and Neuro-oncology focus groups from Adult Clinical Oncology were combined with the Immunology Program to form the new Immunology and Immunotherapy Program. As a consequence, the Program in Immunology and Immunotherapy now has 35 full members holding primary appointments in the Departments of Cell and Structural Biology, Dermatology, Immunology, Medicine, Neurology, Pathology, Pediatrics, Radiology, Radiation Oncology, and Surgery. The group includes the Chair of the Department of Immunology and three members of the National Academy of Sciences. Program members have nearly $12 million in annual direct costs from more than ninety grants. Since the last review, there has been an increase in grants from all agencies, especially the NCI, and NIH. Program members contributed 250 publications, approximately 40 percent involving collaborations with two or more Cancer Center members as authors. Program project initiatives in bone marrow transplantation, melanoma therapy, and control of cell death and differentiation were undertaken. Recruitment of new faculty with interests in human tumor immunology and immunotherapy has been initiated. The Cancer Center provided seed funding to support pilot projects that might evolve into a program project application. Clinical trials in breast, brain, and skin cancer immunotherapy are underway, and promising pre-clinical studies on lung cancer treatment have been made. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IN VITRO MODEL FOR MEASURING SUNSCREEN PROTECTION Principal Investigator & Institution: Hayden, Patrick J.; Mattek Corporation 200 Homer Ave Ashland, MA 01721 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 30-SEP-2001 Summary: (Verbatim) - Excessive exposure to solar radiation results in erythema (sunburn) and has been linked to premature skin aging, immunosuppression and skin cancer. Despite greater awareness by the public of the harmful effects of exposure to sunlight and increased use of sunscreens, skin cancer rates have continued to rise. Currently accepted test methods for determining skin protection factors (SPF) of ultraviolet-B (UVB) sunscreens involve measuring increased UVB irradiation needed to cause erythema in human panelists. However, this test method is sub-optimal because
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of possible risk to human panelists and because the relationship between erythema and skin cancer is unclear. No method is currently accepted for determining protection provided against UVA irradiation, which is also believed to present skin cancer risks. The goal of the present proposal is to develop methodology which overcomes the drawbacks of current sunscreen testing. A mechanistic assay utilizing a highly differentiated skin model and endpoints which directly measure genotoxicity will be used. DNA strand breaks, thymine dimer photoproducts, 8-hydroxyguanosine and p53 protein expression will be determined by various convenient methods. These methods measure events directly related to skin cancer and will give producers and regulators of sunscreens important new tools for assessing the true efficacy of sunscreen formulations. Phase I research will develop methods for determining a sunscreens "DNA protection factor" - the ultimate goal of Phase II research will be to submit results of multi-lab, GLP studies to the FDA for approval as a validated method. PROPOSED COMMERCIAL APPLICATION: The proposed methods for determining genotoxicity in in vitro human skin models will find application in product safety assessment for a broad variety of pharmaceutical, chemical, and consumer product companies. Companies which produce over the counter sunscreen drug products, or other pharmaceutical, cosmetic or household consumer products which may come in contact with skin or are intended for topical use will utilize this technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INDOOR TANNING--YOUTH AND COMMUNITY PRACTICES Principal Investigator & Institution: Forster, Jean L.; Professor; Epidemiology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001; Project Start 27-DEC-1999; Project End 30-NOV-2002 Summary: Skin cancer is the most common form of malignancy in the U.S., and the prevalence is increasing. Evidence is growing to suggest that indoor tanning increases skin cancer risk, and there is reason to believe that the type of UV exposure in indoor tanning may pose a particular risk. Indoor tanning by adolescents is a common, highrisk and unaddressed behavior. This practice is supported by strong social norms about the benefits of having a tan. Indeed, adolescents at highest risk due to their skin type may be most likely to purchase indoor tanning sessions. Interventions to reduce skin cancer risk tested to date have not addressed indoor tanning. Environmental strategies to reduce the likelihood of indoor tanning by adolescents is a promising approach that may complement educational initiatives. We propose a Phase II methods development study to explore the feasibility and effectiveness of an innovative intervention to reduce adolescent indoor tanning by increasing compliance with restrictions on tanning businesses, and reducing adolescent access to those businesses. We will survey adolescents, their parents, tanning businesses and public health officials, and use those data to develop and test an intervention directed at tanning business employees. The primary outcomes of the pilot test will be whether employees of tanning businesses comply with the restrictions and requirements of tanning businesses, including restricting access to an underage buyer without parental permission. As shown for other high-risk behaviors, policy interventions can provide a consistent environmental barrier that enhances the effectiveness of more traditional intervention approaches. This study is conducted in two states (Minnesota and Massachusetts) to reflect between state differences in regulations and their enforcement, and to enhance the generalizability of the results. This Methods Development study is designed to provide the basis for a future intervention trial to determine the efficacy of policy interventions to reduce adolescent use of indoor tanning.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INHIBITION OF TRANSLATION INITIATION IN CANCER THERAPY Principal Investigator & Institution: Halperin, Jose A.; None; Harvard University (Medical School) Medical School Campus Boston, MA 02115 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 30-JUN-2006 Summary: (provided by applicant): Translation initiation factors contribute to initiation of cancer and are required for the maintenance of the transformed phenotype, in part because most oncogenes possess highly structured 5'UTRs and their synthesis is, therefore, highly dependent on translation initiation factors such as elF2. The applicants have discovered that a distinct series of compounds that includes clotrimazole and nonimidazolic triphenyl derivatives, the n-3 unsaturated fatty acid EPA and the thiazolidinediones, which have potent anti-cancer activity in vitro and in animal models, downregulate translation initiation by depleting intracellular calcium stores leading to activation of elF2-kinases that phosphorylate and inhibit elF2alpha Suppression of translation initiation preferentially abrogates the synthesis of Gi cyclins and blocks the cell cycle progression in the Gi phase. Thus, translation initiation inhibitors are now considered an emerging class of mechanism-specific anti-cancer drugs. Using an antibody specific for the phosphorylated form of elF2, we have recently documented that Ca++ releasing TI inhibitors induce phosphorylation of elF2 in animal tumors as they do in cancer cells in vitro, and also shown that Ca++ releasing TI inhibitors induce the expression of ER-stress genes such as BiP and CHOP both in cells and xenografts of human cancers. These results validate in vivo the target-specific mechanism of action of Ca++ releasing TI-inhibitors. In this Application, we propose to establish a novel mechanism-specific animal cancer model for accreditation of translation initiation as a bona fide target for cancer therapy. We also propose to validate the mechanism of action of Ca++ releasing TI inhibitors in human cancers conducting a retrospective study in available tumor samples from patients treated with TZDs and a prospective study in human skin cancers treated with an available topical formulation for 3-5 days before biopsy. Since interferons transcriptionally upregulate PKR expression while Ca++ releasing TI inhibitors turn on its enzymatic activity, we will explore the potential synergism between interferons and TI inhibitors in human cancer xenografts implanted in nude mice. We will also evaluate the relative role of the two ER-resident eIF2 kinases, PKR and PERK, and of the ER-stress gene CHOP, as the downstream effectors of Ca-depleting TI inhibitors. The studies proposed here will pave the way for the development of more potent and less toxic TI inhibitors based on our understanding of their molecular effectors, and for the initiation of human clinical trials to evaluate the efficacy of TI inhibitors for cancer therapy either alone or in combination with interferons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MEASUREMENT ERRORS IN CANCER EPIDEMIOLOGY Principal Investigator & Institution: Rosner, Bernard A.; Professor; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 17-JUL-1989; Project End 31-JAN-2003 Summary: (Adapted from the Applicant's Abstract): The types of exposures studied in cancer epidemiology pose special challenges from a data analytic standpoint. For example, nutritional exposures form the basis for many etiologic hypotheses concerning
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cancer. However, nutrient intake is difficult to measure precisely. The degree of measurement error may mask true underlying relationships due to the regression dilution problem. It is the role of measurement error correction methods to estimate the relationship between cancer incidence and "true" nutrient intake. To accomplish this requires data from both a main study where disease and the surrogate exposure are measured, and a validation study where both the surrogate measure and the gold standard for nutrient intake are assessed. In this proposal, we seek to extend the previous work on measurement error correction which is based on intake reported at a single survey to the situation where diet is reported at multiple surveys over time. Another focus of this proposal is to extend previous measurement error models which were specified at the nutrient level to models specified at the food level, which is the level at which people actually report their intake. The issue is that different foods have different degrees of measurement error, which should be taken into account when considering measurement error both at the food and nutrient level. Another issue is that many nutrients have contributions from both foods and supplements which are likely to have differing degrees of measurement error. We also consider measurement error issues for non-nutritional exposures in cancer epidemiology. For example, proband studies using family registers for a specific type of cancer collect data from a cancer case and other nonaffected people in the same family. Special analytic methods are required to take account of the familial nature of the data. We propose to extend measurement error correction to be applicable to this type of data structure. Second, some exposuredisease relationships are inherently non-linear, and are best captured using splines (e.g., the relationship of skin cancer to low levels of arsenic in drinking water). We propose to extend measurement error correction methods to curves fitted with splines. Also, ROC curves are used in imaging studies for breast cancer detection but are based in imperfect continuous measures. We propose to assess the impact of measurement error on the estimation of the ROC curve. Finally, there is inevitably misclassification in the pathological classification of disease stage in some types of cancer (e.g., pancreatic cancer). We propose to investigate the impact of this misclassification on estimated racial differences in survival for persons with pancreatic cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM AND MODELS OF DNA PHOTOLYASE Principal Investigator & Institution: Wiest, Olaf G.; Chemistry and Biochemistry; University of Notre Dame 511 Main Bldg Notre Dame, IN 46556 Timing: Fiscal Year 2001; Project Start 01-DEC-1997; Project End 30-NOV-2002 Summary: Ultraviolet radiation of DNA causes cell death or skin cancer through formation of cyclobutane pyrimidine dimers (CPD) in the DNA. Many organisms protect their DNA by a light-induced repair mechanism, mediated by DNA photolyase. This extraordinary enzyme restores the genetic information by an electron transfer catalyzed (2+2) cycloreversion of the CPD. Knowledge of the reaction pathways is essential for an understanding of this cancer protection mechanism which is present in many organisms, but probably not in humans. The long term objective of the project is to understand electron transfer catalyzed DNA repair reactions and develop DNA photolyase mimics. Specific aims include: (i) understand the mechanism of cycloreversion at a molecular level; (ii) obtain the electronic and geometric structures of the molecules and transition states involved; (iii) determine the interactions by which DNA photolyase catalyzes the reaction and (iv) design and synthesize efficient, artificial catalysts with DNA photolyase activity. To reach these goals, the electron transfer catalyzed cycloreversion of the cis,syn and the trans,syn cyclobutane uracil dimer as
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well as some simple model systems will be investigated. The mechanistic questions will be addressed by a combination of experimental and theoretical methods. The kinetic isotope effects will be determined using a recently developed methodology. The results will be quantitatively interpreted by quantum mechanical calculations, particularly hybrid density functional methods. Interactions of the radical ions with the solvent and enzyme active site will be calculated by cavity and supermolecule approaches. The information obtained will be applied to the design of molecules that selectively bind either cis,syn or the trans,syn CPD by multiple hydrogen bonding and that are covalently attached to photosensitizers. The quantum yields for CPD repair will be optimized by using charged photosensitzers. These studies will increase our knowledge of DNA repair mechanisms and could ultimately lead to drugs to be used for skin cancer prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM OF ACTION OF THE TRANSCRIPTION REPAIR COMPLEX Principal Investigator & Institution: Bradsher, John N.; Lab De Genetique Moleculaire Des Eucaryo Des Eucaryjotes (Cnrs) Strasbourg, Timing: Fiscal Year 2001; Project Start 01-SEP-1999 Summary: The long-term objective of the proposed training is to provide biochemical evidence for a better model for the human diseases Cockayne syndrome (CS) and combined CS with features of xeroderma pigmentosum (XP/CS). By indication of the clinical manifestations of these diseases, the processes of transcription and/or DNA repair are essential to proper development and neurological function (CS) as well as guarding against predisposition towards skin cancer (XP). Employing active site mutations of CSB and biochemical analysis should allow a determination of which protein consumes ATP and what modifications result from its consumption (e.g. phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (pol II)). Additional investigations seek to characterize the point of assembly of the pol II-CSB complex employing G-less cassette templates and gel shift methods. A second aim will investigate the model of the Pol II-CSB-TFIIH as a functional helicase by probing such complexes with KMn04. Additional investigations seek to determine the defects present in the assembly or activity of the helicase complex among samples from patients suffering from CS and combined XP/CS. The goal is to provide a better understanding of these DNA damage repair disorders. These and other contributions will be essential to the formulation of a better models for the developmental and neurologic diseases characteristic of CS, in addition to the skin cancer predisposition of XP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISM OF TRIPLEX DNA DAMAGE AND REPAIR IN SKIN CELLS Principal Investigator & Institution: Oh, Dennis H.; Dermatology; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Skin cells must respond to DNA damage caused by both environmental exposure as well as therapeutic agents. One response, DNA repair, is the process by which cells recognize, remove and replace lesions in their genomes. Defects in DNA repair underlie several heritable diseases that predispose individuals to skin cancer, photosensitivity and developmental defects. Although impaired repair of
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random DNA damage is deleterious, targeted DNA damage and selective inhibition of its repair in certain genes can be desirable to achieve a therapeutic effect. Triplexforming oligonucleotides (TFOs) that target a DNA damaging agent to a specific nucleotide sequence have emerged as a promising approach for gene therapy. TFOs create structurally unconventional types of DNA damage that can provide insight into the mechanisms of normal DNA repair, that may actually mimic naturally occurring macromolecular interactions that are involved in diseases of the skin, and that have potential to develop into a practical form of cutaneous gene therapy. The overall objective of the proposed project is to understand and manipulate how TFOs target psoralen photoadducts to the interstitial collagenase gene in skin derived cells, and to identify the molecular basis for repair of this unusual macromolecular damage. The hypothesis is that TFO and chromatin structures actively modulate both delivery and repair of a unique form of macromolecular DNA damage, and that novel cellular mechanisms exist to repair this type of damage. To test this hypothesis, the specific aims of the project are: 1) To assess the role of TFO structure in delivery and repair of psoralen photoadduct damage in genomic targets. TFOs with modified backbones will be assessed for their ability to target psoralen photoadducts and mediate their repair in the interstitial collagenase gene; 2) To determine the role of chromatin structure and gene activity in TFO-targeted DNA damage and repair. Exogenous agents that generally or focally disrupt chromatin structure or that alter transcription will be examined for the ability to affect accessibility of TFO target sites to damage and repair; 3) To determine the mechanism of nucleotide excision repair in removal of psoralen adducts targeted by TFOs. Structural TFO variants and human cell lines defective in DNA repair will be used to dissect the role of nucleotide excision repair in processing psoralen photoadducts targeted by different TFOs; 4) To assess the role of cellular helicases in repairing TFO lesions. Cell lines with different helicase activities or deficiencies will be used to determine if these enzymes participate in processing of TFO-mediated damage. At the conclusion of the project period, the proposed work should contribute to our fundamental knowledge of DNA repair mechanisms as well as provide basic principles to guide therapeutic applications of TFOs by manipulating DNA damage and repair. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF CARCINOGENESIS Principal Investigator & Institution: Heck, Diane E.; Assistant Professor; Pharmacology and Toxicology; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, NJ 08901 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Exposure to ultraviolet light, in particular, ultraviolet light B (UVB, wavelengths, 290-320 nm) is known to be a major causative factor in the development of skincancer. The precise mechanisms by which ultraviolet light induces tissue damage are not clear. It hasbeen suggested that cytotoxic reactive oxygen intermediates generated by UVB light in the skin induce DNA damage leading to cancer. In this regard, we have discovered that UVB light rapidly stimulates the production of hydroperoxides by mouse and human keratinocytes in culture in a process that does not require intact cells. Greater amounts of hydroperoxides are produced in calcium-differentiated keratinocytes when compared to growing keratinocytes. Purification studies using homogenates of keratinocytes have identified a major protein responsible for generating hydrogen peroxide in the cells in response to UVB light. This UVB light/peroxide generating activity requires oxygen and is eliminated by heat denaturation. Unexpectedly, sequence analysis identified this protein
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as catalase, an enzyme responsible for the degradation of intracellular hydrogen peroxide to oxygen and water. Our observations that, in response to UVB light, catalase generates reactive oxygen intermediates is highly divergent from the well known antioxidant functions of this enzyme. Our findings that inhibition of the hydrogen peroxide metabolizing activity of catalase with 3-amino-I ,2, 4-trizole or azide markedly enhances the ability of UVB light to generate hydroperoxides provides direct support for our hypothesis that catalase is potentially an important mediator of UVB lightinduced oxidative stress and DNA damage in keratinocytes. To test this hypothesis, we will characterize the production of oxidants by catalase in response to UVB light and the catalase-mediated stress response in both growing and differentiated keratinocytes. We will also evaluate the role of catalase in UVB light-induced carcinogenesis using the mouse skin model. Our proposed studies will provide important insights into the mechanisms by which UVB light induces DNA damage in the skin as well as the role of catalase in UVB light-induced skin cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF INDUCTION OF SKIN CANCERS BY UV LIGHT Principal Investigator & Institution: Ananthaswamy, Honnavara N.; Ashbel Smith Professor and Deputy Chairm; Immunology; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2002; Project Start 01-JUL-1988; Project End 31-MAR-2005 Summary: (provided by applicant): The studies proposed in this grant application are focused on investigating the mechanisms involved in the resistance of CD1 knockout mice to UV carcinogenesis. The rationale for these studies is based on a novel and interesting observation that CD1 knockout mice are extremely resistant to UV carcinogenesis and phototoxicity, and their skin contains a high number of apoptotic keratinocytes compared to CD1+/+ mice. Our recent studies indicate that UV induces the expression of CD1 protein in wild-type mouse skin, suggesting that CD1 is a target for UV. Based on these results, we hypothesize that the resistance of CD1-/- mice to UV carcinogenesis may be associated with persistent elimination of UV damaged, potentially malignant keratinocytes. The following specific aims will be used to test this hypothesis: (1) Determine whether transfection of the CD1 gene into CD1-/- mouse keratinocytes restores resistance to UV-induced apoptosis and susceptibility to neoplastic transformation, (2) Determine whether the increased resistance of CD1-/mice to UV carcinogenesis is due to persistent elimination of UV-damaged keratinocytes from the skin, and (3) Determine whether CD1-/-mouse skin is resistant to UV-induced p53 mutations compared to CD1+/+ mouse skin. To study Specific Aim 1, keratinocyte cultures from neonatal CD1-/- and +/+ will be established and tested for their susceptibility to UV-induced apoptosis, terminal differentiation, and neoplastic transformation. In addition, fibroblasts from CD1-/- and +/+ mice will be tested to determine if the defect is general or limited to keratinocytes. More importantly, CD1 gene will be transfected into CD1-/- keratinocytes to investigate the role of CD1 in UVinduced apoptosis, terminal differentiation and neoplastic transformation. To study Specific Aims 2 and 3, CD1-/- and +/+ mice will be exposed to acute or chronic UV irradiation and their skin analyzed for (i) sunburn and TUNEL-positive cells, (ii) expression of cell cycle and apoptosis-associated proteins such as p53, p21 Waf1/Cip1, Fas, Fas-L, Bax, and Bcl-2, and (ii) kinetics (incidence, latency, and persistence) of induction of UV-specific p53 mutations by allele-specific polymerase chain reaction. Data generated from these studies should shed new light on the role of CD1 in photocarcinogenesis. This information is important for understanding the interactions
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between UV, the CD1 gene, and skin cancer. Although the important role of CD1 molecule in antigen presentation and immune regulation is well known, virtually nothing is known in regard to its role in skin cancer development. Our preliminary findings, resistance to UV carcinogenesis and increased apoptosis in CD1-/- mice, suggest a role for CD1 in cell cycle regulation. Because UV causes immunosuppression and induces skin cancer, and CD1 protein plays a role in antigen presentation and immune regulation, understanding the mechanisms involved in the resistance of CD1-/mice to UV carcinogenesis may also contribute to the understanding of the relationship between UV carcinogenesis and UV-induced immunosuppression. In addition, the results may suggest that similar mechanisms be involved in skin cancer development in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MELANOMA CONTROL FOR SIBLING OF MELANOMA PATIENTS Principal Investigator & Institution: Gilchrest, Barbara A.; Professor and Chair; Dermatology; Boston University Medical Campus 715 Albany St, 560 Boston, MA 02118 Timing: Fiscal Year 2001; Project Start 10-APR-1998; Project End 31-JAN-2004 Summary: With low cost screening and preventive procedures readily available, no one should die of cutaneous melanoma. Promoting melanoma control for at risk populations through regular skin cancer screening and sun protection practices should counter this modern cancer epidemic. Siblings (and other first-degree relatives) of melanoma patients have a two - eight fold elevated relative risk of developing melanoma themselves but have suboptimal knowledge of their risk and limited practice of screening and prevention measures. To date, no intervention protocols have targeted this high risk sibling group, a population estimated to be up to three-quarters million or more Americans. The investigators propose a randomized trial testing personalized telephone counseling intervention support and screening (PERTCISS) that delivers melanoma risk information to siblings and promotes screening and prevention practices. They propose to intervene at a time of a new diagnosis of melanoma in a family member, capitalizing on this teachable moment to reach siblings. They will randomize 450 adult siblings (New England residents) of newly diagnosed melanoma patients to PERTCISS or standard care (SC). The specific aims are to determine, in siblings, the impact of PERTCISS compared to SC on melanoma screening and prevention practices, as well as the knowledge and attitudes that mediate and motivate these practices. They hypothesize that, compared to those in SC, siblings randomized to PERTCISS will demonstrate: 1) Higher levels of three practices: a) physician skin cancer screening examinations, b) skin self-examination for melanoma, c) sun protection practices; and 2) Higher levels of knowledge about melanoma risk and improved attitudes about early detection and prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MITOCHONDRIAL DNA MUTATIONS IN AGING AND NONMELANOMA SKIN Principal Investigator & Institution: Sligh, James E.; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2004 Summary: The development of cancer is generally thought of as the result of many acquired genetic changes that ultimately produce a malignant phenotype. Age-related onset and a history of sun exposure are typical for acquired cases of non-melanoma skin
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cancer (NMSC) which is the most common malignancy of older individuals and represents one of the most common needs for surgical procedures in this population. Inherited or acquired mitochondrial disorders often have an age-related onset. Mitochondria are organelles responsible for generating much of the necessary energy and these organelles contain their own DNA genome. Mitochondria have recently become a focal point for apoptosis research and now tumor biology. The purpose of this study is to test the hypothesis that mitochondrial DNA (mtDNA) is a target of photoaging and that mtDNA mutations play a role in the development of NMSC. This proposal seeks specifically to fully characterize the mitochondrial genome of photoaged human skin, of benign squamous neoplasms, and of NMSC tumor specimens and correlate these findings with observed biological behavior of these lesions. In addition, the functional effects of these mtDNA mutations will be studied in cell hybrid systems for their effect on the growth of non-malignant cells. The insights gained from this research may be useful in our ability to target specific biological behavior of tumor cells with medications as an alternative to surgery for patients with these very common malignancies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOHS EFFECTIVENESS
SURGERY
VS
STANDARD
EXCISION:
COST
Principal Investigator & Institution: Washington, Carl V.; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2004 Summary: Skin cancer in the United States is a large and growing public concern. Nonmelanoma skin cancer (NMSC) frequently occurs in sun-exposed areas such as the face. Two procedures that can be used to remove NMSC tumors are standard excision and Mohs surgery. Our study will compare these two surgical procedures for the treatment of facial NMSC skin in terms of cost, effectiveness, and impact on quality of life (QOL). Our goal is to determine which of the two procedures provides the highest cure rate, at the lowest cost while providing the greatest QOL. Issues such as these may be addressed analytically through the use of cost-effectiveness analyses (CEA). CEA are basic and essential tools used for evaluating health care practices. They measure the relative efficiency of one health care strategy as compared to that of the other strategies. Costs, efficacy, and outcomes are vital components of a CEA. CEA identify variables of the health care pathway that are important determinants of cost and/or outcome. Policy makers can then address these variables to convert a health care plan to a more costeffective one. Our pilot data has provided the cost of the two types of surgical techniques. The specific aims of the proposed project are two fold: the determination efficiency of the two procedures, and impact the procedures have on QOL. This will be done at Emory University where patients who have undergone Mohs surgery will be asked to complete a questionnaire about the impact the scars from a Mohs procedure have on their quality of life. Understanding that CEA compare both costs and outcomes, we hypothesize that Mohs surgery by is more cost-effective and provides greater QOL outcomes than standard surgical excision for facial NMSC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR BASIS OF EPITHELIAL SKIN CANCER Principal Investigator & Institution: Dlugosz, Andrzej A.; Associate Professor; Dermatology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274
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Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2004 Summary: The skin has served as an extremely useful model for studying factors regulating normal epithelial growth and development and the perturbation of these processes that occurs during neoplasia. Although much previous work has centered on squamous cell carcinoma, there has been increased interest in basal cell carcinoma (BCC) following the discovery that deregulated Sonic hedgehog (Shh) signaling is linked to the development of these tumors. Shh pathway activation may be the result of loss-of- function mutations (involving the Shh receptor PTCH1), or gain- of-function mutations (involving SMO, which is normally repressed by PTCH1). While uncontrolled Shh pathway activation is associated with tumor development, we and others have shown that targeted disruption of Shh results in severe impairment of hair follicle morphogenesis. Although it is clear that Shh signaling has important functions in normal skin and BCC, the pivotal nuclear target(s) mediating keratinocyte responses to this pathway have yet to be identified. Much of what is known about this pathway is based on genetic analysis in Drosophila, where the transcription factor Cubitus interruptus (Ci) mediates responses to the Shh homolog Hedgehog. We will explore the notion that one or more of the vertebrate Ci homologs (Gli1, Gli2, Gli3) plays a central role in Shh signaling in keratinocytes. We propose a series of comprehensive studies focusing on the biological, biochemical, and molecular consequences of Gli protein overexpression in keratinocytes. Although there is substantial evidence implicating deregulated Shh signaling in BCC, there is little insight into how activation of this pathway leads to tumor formation. The results of the proposed studies will provide new information to fill in this gap in our knowledge. In addition to BCCs, several other neoplasms have been linked to the Shh pathway, including medulloblastomas and rhabdomyosarcomas. Moreover, precisely-controlled Shh signaling is essential for embryonic patterning in multiple tissues, with deregulation of this pathway leading to a variety of developmental abnormalities. Thus, the knowledge gained during the course of the proposed studies is likely to have relevance to a variety of clinical disorders, and may ultimately lead to improved treatments for BCC and other tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR CHEMOPREVENTION MECHANISMS OF TEA POLYPHENOLS Principal Investigator & Institution: Stratton, Steven P.; Research Assistant Professor; None; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: (Applicant's Description) Prevention is the most efficient way to reduce the incidence, morbidity, Nd mortality of cancer. Thus, development of new investigators in cancer prevention research is imperative. Steven P. Stratton, Ph.D. is a junior investigator in the field of cancer prevention; with training in analytical chemistry, toxicology, pharmacology, cancer therapeutics, cancer drug development, and cancer prevention epidemiology. The mentored training supported by this award will facilitate the development of Dr. Stratton into a fully independent investigator. This project will be conducted at the Arizona Cancer Center, a National Cancer Institute-designated comprehensive cancer center with an international reputation for excellence in cancer prevention research. The proposed studies will be performed under the aegis of the Chemoprevention of Skin Cancer Program Project at the University of Arizona. This project will focus on skin cancer chemoprevention mechanisms with polyphenolic derivatives of tea, Camellia sinensis. Green tea is one of the most widely consumed beverages in the world. Many studies both in vivo and in vitro suggest that
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polyphenolic compounds present in tea inhibit skin carcinogenesis, though the mechanism of action is still unknown. An understanding of this mechanism is crucial to the development of chemopreventive strategies using these compounds. This project will test the hypothesis that green tea polyphenols prevent UV radiation-induced skin carcinogenesis by modulating reactive oxygen-mediated alterations of normal cell function. Markers of reactive oxygen and secondary membrane damage will be used to explore the role of tea polyphenols in UV-induced skin cell transformation using human keratinocytes in vitro and an in vivo mouse skin model. The specific aims of this project include analyzing the effects of green tea polyphenols on: (1) Cell membrane lipid peroxidation using new sensitive and specific GC/MS assays to quantify levels of oxidized biomolecules; (2) Cell cycle progression and expression of cell cycle control genes using flow cytometry and RNase protection techniques; (3) Regulation of transcription factor activation using an alkaline phosphatase reporter system; and (4) Apoptosis and translocation of relevant transcription factors using in situ molecular imaging techniques. Changes in levels of these markers will be used to establish links between antioxidant effects of tea polyphenols and possible direct effects on redoxsensitive downstream events. The overall goal of this project is to promote the development of an academic research career in cancer prevention within a framework of molecular chemoprevention mechanistic studies and training. Immediate goals include acquiring the scientific and technical expertise necessary for independent investigations of secondary cancer prevention mechanisms. Long-term career goals include development of new methods, assays, and expertise in redox-modulated biochemical processes; establishment of a molecular chemoprevention laboratory; development of collaborative research programs in molecular mechanisms of cancer prevention; and ultimately, development of chemopreventive therapies that reduce cancer morbidity and mortality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR EPIDEMIOLOGY OF NON-MELANOMA SKIN CANCER Principal Investigator & Institution: Nelson, Heather H.; Cancer Cell Biology; Harvard University (Sch of Public Hlth) Public Health Campus Boston, MA 02460 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-JUL-2003 Summary: Non-melanoma skin cancer is the most prevalent malignancy in the US, resulting in significant morbidity and health-care expense. Epidemiologic investigations have identified exposure to ultraviolet radiation as the primary risk factor for this disease; other environmental exposures that contribute to risk include ionizing radiation, arsenic, polycyclic aromatic hydrocarbons, and chronic immunosuppression. Host factors associated with increased risk for non-melanoma skin cancer include increasing age, male gender, and sun sensitive skin type. Basal cell and squamous cell carcinomas have been shown to contain alterations in the p53 gene, and recent work has identified a gene on chromosome 9q22, ptch, that is hypothesized to be critical in basal cell carcinoma tumorigenesis. These findings, while informative, are derived from relatively small, selected groups of patients and reflects the paucity of population-based molecular epidemiology for this disease. We propose to expand a large, well-established case-control study of non-melanoma skin cancer in New Hampshire to include investigation of genetic susceptibility. The project will focus on genes that potentially modify ultraviolet radiation exposure, including polymorphisms in the glutathione Stransferases (GSTM1, GSTT1, and GSTP1) and the newly identified variants in DNA excision repair genes (ERCC2/XPD, and XPF). In addition, we will collect tumor
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specimens from cases for characterization of mutations at p53 and 9q22/ptch. We will determine mutation spectra examine associations of mutation with carcinogenic exposures and patient traits, and refine a novel model of skin tumorigenesis. These studies will increase our understanding of host susceptibility to non-melanoma skin cancer and advance current models of skin carcinogenesis through identification of patterns of gene inactivation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: APIGENIN
MOLECULAR
MECHANISM
OF
CHEMOPREVENTION
BY
Principal Investigator & Institution: Pelling, Jill C.; Professor; Pathology and Lab Medicine; University of Kansas Medical Center Msn 1039 Kansas City, KS 66160 Timing: Fiscal Year 2001; Project Start 01-MAY-1996; Project End 30-JUN-2005 Summary: This is a competitive renewal application to investigate the molecular mechanisms involved in skin cancer chemoprevention by apigenin, a nontoxic and nonmutagenic bioflavonoid which inhibits UV-induced skin carcinogenesis when topically applied to mouse skin. During the previous funding period, the applicant investigated the effect of apigenin treatment on expression of the p53 tumor suppressor gene in mouse keratinocytes. In keratinocyte cell lines with wildtype p53 status, the applicant demonstrated that apigenin is extremely potent in elevating the level of wildtype p53 protein in keratinocytes (27-fold). This level of p53 induction is substantially higher than that induced in keratinocytes by UVB irradiation, for example (5-fold). The applicant further demonstrated that the increased level of p53 protein was due to protein stabilization, accompanied by increased phosphorylation of p53 at Ser15 and subsequent transcriptional activation of p53-responsive genes including p21WAF1. Interestingly, the applicant did not observe any increased accumulation of MDM2 protein in apigenin-treated cells, which is unexpected considering that the MDM2 gene is a downstream target of p53 transcriptional activation and generally responsible for feedback inhibition of p53 by promoting its degradation through ubiquitination. The applicant's results indicate that apigenin treatment of keratinocytes induces many of the same events in the p53 pathway that are normally triggered during the cellular UV DNA damage response, with the exception that the negative feedback MDM2 control loop appears to be absent. The lack of feedback inhibition by MDM2 may prolong the beneficial effects of p53 protein stabilization in apigenin-treated keratinocytes. The hypothesis to be tested in this renewal application is that apigenin's chemopreventive activity is derived from its ability to enhance the response of the normal cellular p53 pathway to UV-induced damage in keratinocytes. The applicant proposes four specific aims to test this hypothesis: (1) Investigate the mechanism(s) by which apigenin treatment induces posttranslational modification of p53, by identifying the p53 phosphorylation sites, the kinases involved in phosphorylation, and whether apigenin induces p53 acetylation in keratinocytes; (2) Having characterized p53 protein posttranslational modification induced by apigenin treatment alone, investigate the combined effects of apigenin treatment plus UVB irradiation on p53 protein levels, stabilization, and post-translational modification; (3) Investigate the impact of apigenin treatment on MDM2 gene expression, on interaction of p53 and MDM2 protein, and whether apigenin treatment results in inhibition of MDM2-mediated p53 ubiquitination and degradation; (4) Investigate the combined effects of apigenin treatment plus UVB irradiation on MDM2 gene expression, MDM2/p53 protein interaction, and MDM2/p53 protein interaction, and MDM2-mediated p53 ubiquitination. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR STAGING OF HUMAN SQUAMOUS CELL SKIN CANCER Principal Investigator & Institution: Gale, James M.; Assistant Professor; Cell Biology and Physiology; University of New Mexico Albuquerque Controller's Office Albuquerque, NM 87131 Timing: Fiscal Year 2001; Project Start 18-SEP-2000; Project End 31-AUG-2002 Summary: (Applicant's Description) Lifetime risk for developing skin cancer is currently l in 5 for the USA. While the non-melanoma skin cancers (basal and squamous cell) are generally not life threatening (2-5 percent of squamous cell carcinoma will become metastatic), they account for substantial morbidity and health-care expenditures. Our understanding of the molecular pathology and critical gene-networks involved with the development and progression of non-melanoma skin cancers is incomplete, resulting in poor markers for progression, prognosis and largely ineffective treatments for invasive stages. The broad objective of this proposal is to characterize the changes in gene expression in different stages of squamous cell carcinoma (SCC) to identify the different gene pathways involved. To characterize the most complete geneexpression profile currently possible, a set of reusable nylon microarrays containing 30,000 different human cDNA's (all of the approximately 7,000 "named" genes and EST's of unknown function) will be used. SCC is well suited for an initial human cancer study because (a) there is a better consensus about the clinical stages of the disease, (b) samples of SCC are relatively easy to obtain from the clinic, and (c) SCC is most associated with sun-exposure (most frequently found on sun-exposed skin and over 90 percent of SCC tumors have p53 mutations, mostly of the type caused by UV). Of the new technologies available, cDNA microarrays have ability to screen a huge portion of all human genes (30,000 of approximate 100,000 total human genes) with the expected potential to identify "all" the genes whose expression has been changed at different stages of cancer. The specific aim of the R33 component of this proposal is to profile the gene-expression levels in the three most distinct stages of the disease (actinic keratoses; a pre-malignant lesion, SCC and metastatic SCC) from 24 subjects (12 men and 12 women, 8 subjects in each lesion group). The necessary controls of normal-uninvolved skin will be obtained by punch biopsy from both the forearm (sun-exposed skin) and the buttocks (sun-protected skin). Having two normal skin controls will add power to the data analysis and help identify genes that are naturally responsive to sunlight (may be involved in early stages of skin cancer or show natural high variability in skin which would confuse the comparison with SCC lesions). Moreover, the potential power of reusable microarrays (multiple stripping and probing) is the ability to compare results between arrays. Once the variability-profile of comparing many microarrays is calculated (hybridization of 5 microarrays with the same probe, a milestone of this proposal), we will calculate the average and standard deviation for each of the 30,000 cDNA's for the sun-exposed skin controls and sun-protected skin controls form both the 12 men and 12 women in the study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEW THARAPY FOR HER 2/NEU POSITIVE BREAST CANCER Principal Investigator & Institution: Dannenberg, Andrew J.; Medicine; Weill Medical College of Cornell Univ New York, NY 10021 Timing: Fiscal Year 2001; Project Start 15-JAN-2001; Project End 31-DEC-2004 Summary: Amplification or overexpression of HER-2/neu occurs in 20-30 percent of human breast cancers, and increased expression has been associated with poor
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prognosis in the patients. New medications are urgently needed to treat this disease. Several lines of evidence suggest that COX-2 is important in carcinogenesis. COX-2 deficiency protects against intestinal and skin tumor formation in experimental animals. The applicant has discovered that levels of COX-2 are elevated in HER-2/neu-positive human breast cancer. This raises the possibility that selective COX-2 inhibitors will prevent neu-induced mammary tumorigenesis, as was recently shown for colon and skin cancer. One aim of this proposal, therefore, is to determine whether pharmacological inhibition or genetic ablation of COX-2 suppresses the formation of or inhibits the metastasis of mammary tumors in MMTV/neu transgenic mice. There is also growing preclinical evidence that ligands of the nuclear receptor PPAR gamma may be effective in preventing or treating breast cancer. The applicant has shown that PPAR gamma ligands inhibit the growth of HER-2/neu-transformed mammary epithelial cells and suppressed HER-2/neu-mediated activation of COX-2 gene expression. A second aim will be to determine whether troglitazone, a PPRP gamma ligand, prevents mammary tumorigenesis in MMTV/neu transgenic mice or enhances the antitumor activity of Herceptin. Finally, the applicant will elucidate the mechanisms by which PPAR gamma ligands cause G1 cell cycle arrest and inhibit HER-2/neu-mediated induction of COX- 2. The results of these studies will provide the basis for making a rational decision about whether selective COX-2 inhibitors or PPAR gamma ligands should be evaluated in women with HER-2/neu-overexpressing breast cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NUTRITIONAL PREVENTION OF CANCER Principal Investigator & Institution: Marshall, James R.; Professor of Public Health & Medicine; Roswell Park Cancer Institute Corp Buffalo, NY 14263 Timing: Fiscal Year 2002; Project Start 15-AUG-1988; Project End 31-AUG-2004 Summary: (provided by applicant): The results of the Nutritional Prevention of Cancer Trial (NPC) substantially impacted the evidence supporting selenium as a chemopreventive agent. These results, published in 1996, have been cited in the medical literature over 400 times in the last five years and have received considerable public attention. The original trial randomized 1312 subjects, all non-melanoma skin cancer (NMSC) patients, to 200 mcg/day of selenium or a matching placebo. In a second trial, 424 subjects, also NMSC patients were randomized to 400 mcg/day of selenium or placebo. Although the NPC study did not support a protective effect of selenium on the recurrence of NMSC, a 200mcg/day supplement of selenium in Baker's yeast significantly decreased total cancer mortality and incidence, as well as the incidence of cancers of the lung, colon and prostate. A preliminary analysis of the 400 mcg/day dose showed no significant difference in cancer incidence between the two treatment groups. After the publication of these startling results, the blinded phase of the trial ended and all subjects were offered the opportunity to take 200 mcg/day selenium supplements (Open-Label Phase). The Open-Label Phase has actively followed approximately 937 (54%) of the original participants from both trials since 1996. Approximately 553 (32%) chose to take the supplied selenium supplements. Every 6 months, all participants are assessed for incident cancers and other significant illnesses, signs and symptoms of selenium toxicity, and vital status. To date, 714 (41%) are deceased and 13 (0.7%) are lost to follow-up. The large and detailed database generated from the NPC trial, which has been routinely updated, is supplemented with more than 40,000 archived plasma samples collected throughout the trial. This proposal requests a final funding period for the NPC Trial and outlines three main goals of the next 3 years. These goals include: 1 ) based on the Data Safety Monitoring Board (DSMB) recommendations, to end the Open-
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Label Phase and stop active follow-up through a planned sequence of mailings and contacts; 2) to complete the documentation of reported illnesses and procedures and the vital status of all original participants in the two trials; and 3) to complete the reanalysis of the major endpoints, including major cancers and cardiovascular diseases.The Principal Investigator, Dr. James Marshall will be relocating to Roswell Park Cancer Institute (RPCI) as of July 2002. He will make frequent visits to Tucson to continue active oversight of the completion of this important project. To maintain oversight continuity, Dr. Mary Reid will serve as the Arizona-based PI. Utilizing her past experience as project director of NPC and research role as Research Director, she will continue to supervise the project staff, direct the management and analysis of the data, and work with Dr. Marshall and Dr. Anna Lillico to plan for manuscript preparation and publication. The project staff will otherwise remain the same, ensuring the efficiency and high quality data management that has characterized this trial. The proposed project will complete the data collection for the NPC trial and will utilize this invaluable resource to verify the effects of selenium supplementation through a series of publications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NUV RESISTANCE-- FUR-DEPENDENT REGULATION OF RPOS. Principal Investigator & Institution: Hoerter, James D.; Biological Sciences; Ferris State University 901 S State St Big Rapids, MI 49307 Timing: Fiscal Year 2000; Project Start 01-JUN-2000; Project End 31-MAY-2004 Summary: The depletion of the global stratospheric ozone shield is leading to a rise in the level of near-ultraviolet radiation (UVB-290-320 nm) reaching the earth's surface. Humans are also exposed to NUV radiation through the use of tanning beds. Increases in near-ultraviolet radiation are believed to be responsible for the dramatic rise in the incidence of skin cancer.: The overall objective of this lab is to identify specific biological mechanisms involved in the damage, protection and recovery from near- ultraviolet radiation. Escherichia coli will be used as a model organism to investigate the relationship between the genes that controls iron uptake (ferric uptake regulator; fur) and the stationary-phase sigma factor (rpoS). RpoS is a central regulatory component in bacteria for the defense against near-ultraviolet light (NUV; 290-400 nm). Hydroperoxidases, HPI and HPII, are members of the RpoS regulon. The specific aim of this study is to determine the levels at which Fur and RpoS interact to regulate cellular response to NUV irradiation and other stresses. If the Fur protein plays a key role in iron-dependent activation of rpoS regulon, mutants that affect the uptake, release and utilization of iron will be excellent genetic tools to determine the locations in the iron uptake and supply pathways that influence rpoS activity. This study will also determine whether the Fur protein is involved in an oxyR- dependent pathway regulating catalase activity. Catalase activity will be assayed at different phases of the cell's life. Utilizing oxyR and rpoS mutant strains that are known to regulate HPI and HPII at different stages of the cell's life cycle, we will be able to determine the role of Fur in contributing to the levels of HPI and HPII during both stationary and exponential phases. The effect of iron availability on the activity levels of HPI and HPII catalase will be determined in iron-rich and iron- deficient media. Regulation at the transcriptional level will be conducted using rpoS: :lacZ and katG::lacZ and katE: :lacZ promoter fusions. Overall this study will help identify other cellular conditions and genes that regulate RpoS activity, and unravel the complex mechanisms that regulate catalase synthesis and other cellular defense mechanisms against NUV radiation. This research will provide training
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opportunities in research for undergraduate students enrolled in pre-professional programs in optometry and pharmacy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OLEANDRIN: A NOVEL SKIN CANCER CHEMOPREVENTIVE AGENT Principal Investigator & Institution: Mukhtar, Hasan; Professor, Vice Chair and Director of Re; Medicine; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2002; Project Start 03-JUL-2002; Project End 30-JUN-2004 Summary: (provided by applicant): The search for ideal agent(s) in the armamentarium of cancer chemoprevention continues. Agents capable to intervene at more than one critical pathway in the carcinogenic process will have selective advantage over other single-target agents. Based on the impressive array of structures and activities plantbased polyphenols are showing promise as cancer chemopreventive and often as cancer therapeutic agents. Based on our recent exciting preliminary data and published studies there is a strong possibility that oleandrin, derived from the leaves of Nerium oleander may be developed as a novel chemopreventive agent. Because of the established role of ornithine decarboxylase (ODC) in tumor promotion and nuclear factor kappa B (NF-kB), in regulating the transcription of a variety of genes involved during the promotion stage of cancer these two are important targets to block tumor promotion phase of the carcinogenesis process. The central hypothesis to be tested in this proposal is that oleandrin will afford protection against the development and progression of skin tumorigenesis by 12-O-tetradecanoylphorbol-13-acetate (TPA) application in 7, 12dimethybenz(a)anthracene (DMBA)-initiated mouse skin by blocking ODC induction and by reducing NF-kB activation. Under the proposed specific aims we will investigate the (i) effect of oleandrin treatment on TPA-caused activation of NF-kB pathway in SENCAR mouse skin, (ii) effect of topical application of oleandrin on DMBA-initiated, TPA-promoted skin tumorigenesis in SENCAR mouse, and (iii) establish if the antitumor promoting effects of oleandrin are mediated via inhibition of ODC induction by employing K6/0DC overexpressing transgenic mice, which develops skin tumors following tumor initiation (by DMBA), without the need of any exogenous promotion protocol. Successful completion of this proposal will lay the foundation for an extended program to develop oleandrin as future promising cancer chemopreventive and/or therapeutic agent in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OLIGOSACCHORIDE TECHNOLOGY TO PREVENT SKIN CANCER Principal Investigator & Institution: Waller, Todd A.; Pangea Phytoceuticals 306 E Jackson, Ste 119 Harlingen, TX 78550 Timing: Fiscal Year 2001; Project Start 26-FEB-1999; Project End 31-MAR-2002 Summary: Skin cancer, the most frequently diagnosed malignancy, with over 800,000 new cases per year, has a steadily rising incidence. The major environmental carcinogen, solar UV radiation, causes skin tumors in two ways: (i) as a mutagen for skin cells and (ii) as a suppressant of tumor surveillance. Exposure of skin to UV radiation suppresses T-cell responses to antigens encountered in the skin and permits the growth of highly immunogenic skin cancers in laboratory animals. Although sunscreens reduce inflammation, they often lead to increased exposure. We have previously shown that crude extracts of Aloe barbadensis protect T-cell responses in mice when applied up to
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24 hours following exposure to UV radiation. Aloe does this by virtue of at least two chemically and mechanistically different pharmacological systems one of which involves a cleavage oligosaccharide that downregulates the production of an immunosuppressive cytokine, Interleukin-10, by UV injured keratinocytes. In Phase I we established parameters and procedures for the controlled cleavage of the cytoprotective oligosaccharide from the native polysaccharide. In Phase II we will scaleup the process, develop real time quality control procedures and chemically characterize the biologically active oligosaccharide. PROPOSED COMMERCIAL APPLICATIONS: Oligosaccharides will be isolated by cellulose cleavage from native Aloe barbadensis gel. These will be suitable as therapeutic agents for use in a post sun car preparation designed to prevent injury by UV radiation to the skin immune system. Such a preparation has potential for the prevention of sun- induced skin cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OPTICAL MAPPING OF NONMELANOMA SKIN CANCERS Principal Investigator & Institution: Yaroslavsky, Anna N.; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): More than a million cases of non-melanoma skin cancers (i.e. basal cell and squamous cell carcinomas) are diagnosed every year. These cancers are more common than all other human cancers. Almost all basal cell and squamous cell carcinomas are curable by surgery if detected early. Unfortunately, in most cases the contrast of the lesions is poor, which complicates tumor localization and precise excision. Treatment of cancer patients could benefit greatly if a real-time noninvasive, reliable and cost-effective technique for delineating tumor margins were available. Therefore there is a strong need for practical, reliable, rapid, and precise methods for tumor localization, to guide surgery and other treatments of skin cancer. Once developed, such methods may potentially be useful for epithelial cancers of other organs. The overall goal of this proposal is to develop a practical way to detect skin cancer margins and guide tumor excision surgery using non-invasive optical imaging techniques. Specifically, spectrally resolved and polarization sensitive imaging methods and equipment, which are applicable for both reflectance and fluorescence imaging will be developed and implemented. The specific aims are: (i) Design and build multispectral polarization-enhanced reflectance and fluorescence imaging system for in vivo localization of skin cancers that can rapidly image large tumor affected areas in clinical setting. (ii) Develop methods for reliable localization of skin tumors based on polarized light reflectance imaging, dye enhanced polarized light reflectance imaging, and exogenous dye fluorescence-depolarization imaging. (iii) Develop and verify algorithms for quantitative assessment of skin tumor localization. (iv) Integrate the developed algorithms and imaging techniques into an efficient bedside guidance tool for tumor localization and excision. (v) Evaluate the clinical prototype and the developed imaging methods in a surgical practice environment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PATIENT ORIENTED RESEARCH IN CUTANEOUS ONCOLOGY Principal Investigator & Institution: Lessin, Stuart R.; Fox Chase Cancer Center Philadelphia, PA 19111 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-JUN-2004
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Summary: This is a Midcareer Investigator Award in Patient-Oriented Research (POR) application (K24) for Stuart R. Lessin, M.D and will focus on cutaneous oncology. Dr. Lessin is Associate Professor and Co-Director of the Cutaneous Lymphoma Program in the Department of Dermatology at the University of Pennsylvania. He is highly committed to POR and has a well established track record (funding and publications) in the area of cutaneous T-cell lymphoma (CTCL). He has developed techniques for the molecular diagnosis of lymphoproliferative skin diseases based on T-cell receptor (TCR) gene expression and translated them into new strategies of therapy utilizing the TCR as a target. Dr. Lessin is currently the principal investigator of a FDA funded Phase I clinical trial testing the safety and efficacy of genetic (DNA) vaccination of human TCR in patients with CTCL. The overall research goal of this proposal will be to develop and test novel therapeutic approaches to skin cancers utilizing the technologies of therapeutic DNA vaccines, peptide vaccines and peptidomimetics. Dr. Lessin has been heavily involved in the mentoring and training of trainees in POR at all levels - medical students, residents/fellows and junior faculty. This has been accomplished through a series of well established POR programs. Currently, Dr. Lessin serves as a mentor in the Department of Dermatology's Cutaneous Oncology Fellowship Program, NIH Training Grant (T32), Drug Study Unit, Derm 800 Research elective and Junior Faculty Mentor's Program. The University of Pennsylvania's commitment and ability to provide opportunities and facilities necessary for POR is extraordinary. A well established Core Curriculum in POR Training, a NIH sponsored General Clinical Research Center (GCRC) and outstanding interaction between basic and clinical investigators provides a unique and dynamic environment in which to conduct and train individuals in POR. Dr. Lessin will participate in the POR core curriculum and the GCRC. This award will provide a critical infrastructure for Dr. Lessin to pursue POR and to mentor other investigators in POR. A commitment of 50 percent effort will ensure the continued acquisition of funding and protected time for clinical testing of new therapies. Furthermore, it will enable Dr. Lessin to continue to participate in the ongoing departmental and institutional POR programs and serve as a role model and mentor for young investigators in POR at the University of Pennsylvania. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PERCEPTION OF GENE-ENVIRONMENT CANCER RISKS IN MELANOMA Principal Investigator & Institution: Hay, Jennifer L.; Instructor; Sloan-Kettering Institute for Cancer Res New York, NY 10021 Timing: Fiscal Year 2003; Project Start 08-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The overall goal of this career development application is to launch an independent research program on perception of geneenvironment cancer risks. There is mounting evidence that common genetic polymorphisms can either accentuate or attenuate environmental risks, such as smoking and sun exposure, and that these interactions are a primary etiological pathway to carcinogenesis. In the coming years, it is likely that a growing number of individuals will receive probabilistic information concerning genetic and environmental cancer risk factors. The number of individuals who are affected will exceed those with uncommon, highly penetrant single-gene mutations. Existing research on cancer risk communication targeted to those with single risk factors, such as genetic mutations alone, or lifestyle risk factors alone, do not adequately address the potential challenges and prevention opportunities presented by our increasingly comprehensive understanding of environmental and genetic risk interactions. Gene-environment interactions are
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implicated in the etiology of a number cancer sites. Melanoma will provide the paradigm for study in this application because of the evidence for gene-environment etiology, rising incidence rates, and promise of behavioral prevention. Given the current absence of identified germ line mutations, studying first-degree relatives of melanoma patients will provide a vehicle in the proposed studies to examine the role of geneenvironment risk perceptions and both skin cancer screening and sun protection behavior. Study I is a qualitative interview study of risk perceptions among first-degree relatives of melanoma patients. Study II is a prospective assessment of risk perceptions, skin cancer screening, and sun protection behaviors among first degree-relatives of recently diagnosed melanoma patients. Through intensive interaction with multidisciplinary colleagues, formal epidemiology coursework, teaching, and research, this career development award will establish my multidisciplinary research skills at the interface of genetic epidemiology and behavioral science, and position me to establish novel theory and measurement strategies for the role of risk perceptions of geneenvironment interactions, and ultimately to develop communication models of geneenvironment cancer risks which will be applicable to other cancer sites. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHASE IIB STUDIES FOR PREVENTION OF NONMELANOMA SKIN CANCER Principal Investigator & Institution: Levine, Norman; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2001 Summary: The overall goal of this Program Project is to develop safe and highly efficacious intervention strategies for prevention of melanoma and non- melanoma skin cancers (NMSC) and to develop basic science and clinical research approaches which will serve as models for the chemoprevention of a wide range of human epithelial cancers. Approximately 60% of squamous cell carcinomas (SCC) arise from pre-existing actinic keratoses (AKs) and/or contiguous skin surfaces. Researchers agree that the probability of successfully altering the natural history of any cancer increases by targeting an earlier, rather than a later, time point in carcinogenesis. Therefore, in this Project we propose to conduct two phase IIb randomized placebo-controlled doubleblinded, cancer prevention clinical trials in individuals with preclinical AKs. The chemoprevention agents to be used are those identified in prior phase IIb studies as well as in our current Projects. Recently, in a phase III trial in 2297 participants with greater than or equal to 100 AKs, we found that daily supplementation of 25,000 IU of oral vitamin A for 5 years was effective in preventing SCC [hazard ratio of o.74 (95% C.I.: 0.56 - 0.99, p = 0.04) for a few SCC, comparing subjects receiving vitamin A versus placebo]. In this study , oral vitamin A (retinyl palmitate) at 25,00 IU/day and 50,000 IU/day (doses which proved non-toxic in our previous phase IIa study) will be compared to topical 0.1 tretinoin administered for 6 months. In this study, topical tretinoin will be used as a positive control in comparison to two topical chemoprevention agents identified by the results of a concurrent of Project difluoromethylornithine (DFMO), epigallocatechin gallate (EGCG); 9-cis-retinoic acid; or perillyl alcohol. We propose to demonstrate that specific histopathologic and morphometric abnormalities, genetic alterations, and immunohistochemical surrogate endpoint biomarker (SEB) changes can be modulated safely by chemoprevention agents. During these clinical studies we will determine the predictive accuracy of ultraviolet and polarized photography with respect to identification of abnormal histopathologic and morphometric areas of forearm skin epidermis, and ultimately, examine the
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histopathologic/morphometric preneoplasia.
and
molecular
genetic
pathogenesis
of
skin
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHOTOPROTECTION OF SKIN BY TOPICAL SELENIUM Principal Investigator & Institution: Omar, Mostafa M.; Phytoceuticals, Inc. 37 Midland Ave Elmwood Park, NJ 07407 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 29-SEP-2003 Summary: (provided by applicant): Ultraviolet (UV) radiation causes oxidative damage to skin which can cause skin cancer, alter the behavior of skin cancer (typically making the cancer more aggressive), and/or cause photoaging. Topical selenium compounds may prevent this damage. In an attempt to moderate UV-induced photodamage, we will formulate topical selenium products and test them in pig skin. Formulations - including selenium sulfite, L-selenomethionine, selenotrisulfide, derivatives of lipoic acid and lipoamide - will be tested for percutaneous absorption in pig skin. Those formulations having the best characteristics will be chosen for further study. We will irradiate normal pig skin with UV radiation. We will assess histological changes and quantitate damage by measuring apoptosis, nucleic acid oxidation, and matrix metalloproteinase induction. We will determine the relative protection of topical selenium formulations to inhibit photodamage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PIK RELATED KINASES IN THE RESPONSE TO DNA DAMAGE BY UV Principal Investigator & Institution: Nghiem, Paul X.; Chemistry and Chemical Biology; Harvard University Holyoke Center 727 Cambridge, MA 02138 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: The candidate is an M.D./Ph.D. who completed clinical training in dermatology in June 1997. He is now pursuing basic research with the goal of a career as an independent investigator. The research is being carried out under the sponsorship of Dr. Stuart Schreiber in the Department of Chemistry and Chemical Biology at Harvard University. The Schreiber group has a major focus on understanding and controlling the cell cycle using genetic and biochemical approaches. DNA damage by solar ultraviolet (UV) radiation is the major cause of skin cancer, the most common type of cancer in the US. A cellular "UV response" involving activation of the p53 tumor suppressor protein has evolved to protect the genome against this solar threat. An intact response leads to cell cycle arrest and allows DNA to be repaired prior to replication preventing the permanent incorporation of mutations. Roughly 90% of squamous cell carcinomas cell carcinomas lack this UV response indicating the essential function of the pathway in protecting the genome from UV carcinogenesis. Despite the importance of this protective pathway, it is not known how DNA damage by UV leads to p53 induction. A gene called ATR has been cloned in the Schreiber group and appears likely to be the mediator of the UV-p53 response based on preliminary data. ATR belongs to a newly described family of proteins called the PIK-related kinases (phosphatidyl inositol kinase-related kinases), which mediate cell cycle arrest after cellular stresses such as DNA damage. Molecular and biochemical approaches will be used to test the hypotheses that ATR or another PIK-related kinase is required for the UV response. Endogenous ATR function will be inhibited with a dominant negative ATR allele expressed in an inducible or retroviral system. The role of ATR will then be examined in
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individual aspects of the response to UV-DNA damage. Later studies will focus on other proteins in this pathway including putative substrates for the UV-responsive protein. This project will update and expand the candidate's molecular and cellular biology experience and train him in the field of cell cycle regulation, facilitating future independent work in cancer biology. Scientifically it aims to provide insight into UV carcinogenesis and may suggest approaches for the prevention and treatment of skin cancer and cancer more generally. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PILOT--CUTANEOUS ONCOLOGY Principal Investigator & Institution: Johnson, Timothy M.; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 30-SEP-1988; Project End 31-MAY-2006 Summary: The Cutaneous Oncology Program was initially established as a developmental program and achieved full programmatic status in 1996. Its mission is to utilize knowledge gained from basic, preclinical, and clinical research endeavors to improve the overall care of patients with skin cancer. We believe that understanding the biology of melanoma and non-melanoma skin cancers will drive future innovations in prevention, diagnosis, and treatment. The program now consists of 15 investigators from 9 Departments, with over $3.2 million dollars in annual direct funding for basic and clinical research activities. Basic research efforts are focused on areas that have relevance to all forms of cutaneous neoplasia, including the investigation of molecular, biochemical, cellular, and tissue alterations driving the development and progression of skin cancer. A major new initiative is aimed at developing mouse models of human skin cancer for basic and preclinical studies. The clinical research program has made important advances using innovative, immune-based therapies for melanoma. Given the importance of early detection, additional efforts in melanoma are focused on the development of improved patient-education materials, while other work is aimed at better understanding the psychosocial and behavioral repercussions of being diagnosed with melanoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PILOT--FGF AND SPROUTY2 IN MOUSE SKIN DEVELOPMENT Principal Investigator & Institution: Minowada, George; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2006 Summary: Several mechanisms can cause increased Ras signaling, which is a common finding in many human cancers. Activating mutations in Ras are commonly found in skin cancers. Genetic studies in the mouse showed that gain of function perturbations in the Ras signaling pathway increased skin tumor susceptibility or were sufficient to cause tumors. Other studies indicated that p53, p16(INK4a), and p19(ARF) tumor suppressor function played critical roles in determining if keratinocytes underwent malignant transformation in response to increased Ras signaling. Classically, extracellular growth factors bind to and induce dimerization of transmembrane receptor tyrosine kinases (RTKs), which initiates the RAS/MAPK intracellular signaling cascade. Upregulation of the Epidermal Growth Factor Receptor (EGFR) family and/or their ligands is a common finding in skin cancer. Consequently, their role in the pathogenesis of skin cancer has been the focus of many studies. Much less is known about the possible role of Fibroblast Growth Factor Receptor (FGFR) initiated Ras signaling in skin
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tumor development. Keratin 14 (K14) promoter driven misexpression of keratinocyte growth factor (kgf aka Fgf7) in the epidermis, at relatively high levels, caused skin abnormalities that were perinatal lethal in 13/18 founders. The 5 surviving pups had lower transgene expression, but also displayed a range of skin phenotypes. Interestingly, discreet areas of skin showed signs of transformation at 4 months of age, but it is not known if these changes progressed to tumors. Because the K14 promoter begins to be expressed in the developing epidermis at about embryonic day 14.5, it is difficult to determine to what extent the observed phenotypes were due to developmental defects. Thus, the consequences of increased, particularly greatly increased, FGFR signaling in postnatal skin remains unclear. Here, we propose to use an inducible K14 Cre transgene to recombine a highly expressed, conditional Fgf4 transgene and thereby misexpress high levels of Fgf4 in the skin of postnatal mice. The specific aims of the project are (1) to characterize the histological and molecular changes that occur in the skin over time in response to postnatal increased FGFR signaling; (2) to determine if prolonged, increased FGFR signaling leads to skin cancer. The proposed studies will provide insights into the potential role of FGFR signaling in the pathogenesis of skin cancer. In addition, because of the great interest in KGF-based therapies to promote wound healing, a greater understanding of the consequences of increased FGFR signaling in the skin is important to prevent potentially detrimental side effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PILOT--METHYLATION PROFILES OF TUMOR SUPPRESSOR GENES IN SKIN CANCERS Principal Investigator & Institution: Gazdar, Adi F.; Professor; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: Specific aims: Aim 1. Collect skin tumors (approximately 40 squamous cell (SCC) and basal cell (BCC) carcinomas (approximately 40 each) and malignant melanomas (MM)(approximately 20). Skin tags will be collected from sun exposed (approximately 50) and non exposed (approximately 25) skin of adults. Aim 2. We will select a panel of 15 tumor suppressor genes involved in growth cycle regulation, apoptosis, cell adhesion, differentiation, tissue invasion and metastasis and which are known to be down regulated in many tumor types by aberrant gene methylation of promoter regions. We will determine the methylation profile of our tumor and skin samples. Aim 3. We will compare and contrast the methylation patterns of the major forms of skin cancer and between sun exposed and non exposed skin samples. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PILOT--PAPILLOMAVIRUS AND UV LIGHT DEPENDENT SKIN CANCER Principal Investigator & Institution: Rorke, Ellen A.; Associate Professor; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001; Project Start 30-SEP-1988; Project End 30-APR-2006 Summary: Ultraviolet B (UVB) irradiation and human papillomavirus (HPV) have been suggested to act as cancer promoting cofactors in epidermis, as epidermal squamous cell carcinomas frequently harbor high risk HPV subtypes and appear in sun-exposed skin. The high risk HPV subtypes are thought to immortalize cells via the action of the E6 and E7 viral oncoproteins, and, as a result, predispose the cells towards cancer progression.
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These oncoproteins interfere with the function of the p53 and Rb tumor suppressor proteins and alter events at the G1/S interface of the cell cycle. In addition to HPV infection, conversion to malignancy requires subsequent mutation of host cell DNA. It has been suggested that ultraviolet light, a powerful mutagen, may serve to produce these mutations. Unfortunately, cancer-promoting synergy between HPV and UVB has not been definitively demonstrated, in vivo. To study the role of HPV in surface epithelial cancer, we have developed a mouse model of HPV-dependent epidermal disease by expressing the human papillomavirus type 16 E6/E7 oncoproteins in the superficial epidermal layers. These mice display marked epidermal hyperplasia, but not tumor formation-a phenotype that is a hallmark of early HPV-dependent disease. To evaluate the relative contribution of HPV and UVB in skin cancer progression, we will compare the effects of UVB irradiation on disease progression in E6/E7-negative mice. We hypothesize that the presence of the HPV oncoproteins will predispose the mice to UVB- dependent cancer progression. As the HPV oncoproteins and UVB are both known to alter the function of key regulatory proteins in the G1/S transition of the cell cycle, we will focus our effort on studying these regulatory events. We will examine the level, functional activity, and tissue distribution of p53 and Rb (and associated proteins), the cyclins, the cyclin-dependent kinases (cdk), and the cyclin-dependent kinase inhibitors (cdki) during disease progression. The proposed studies are designed to provide new information regarding the role of HPV in each stage of disease progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MELANOMA
POLARIZATION
SENSITIVE
OCT
FOR
DETECTION
OF
Principal Investigator & Institution: Gulsen, Gultekin; Assistant Researcher; Ctr for Functional Onco-Imaging; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2004 Summary: (provided by applicant): Optical Coherence Tomography (OCT) is a recently developed imaging technology, which permits in-situ, real-time, non-invasive, noncontact, cross-sectional imaging of micron-scale structures in biological tissues and as such seems to be a suitable modality for the study of skin cancer. The development of polarization sensitive optical coherence tomography (PS-OCT) permits the acquisition additional information on the polarization properties of tissue carried by the reflected light. Malignant melanoma, a form of skin cancer, is increasing in incidence at the most rapid rate of all cancers. Yet detection of melanoma visually, even by experts in melanoma, has only 60-80% sensitivity. Thus, new methods of analyzing suspicious skin lesions in vivo are urgently needed. In this proposed study, we will construct a PS-OCT system to distinguish between normal, benign and malignant tissues. The PS-OCT system will control the polarization state of the light incident upon the sample. By measuring the reflectivity of light returning in particular polarization states we will obtain the Mueller matrix that provides complete representation of the polarization properties of the sample. During the first year of this project, we will complete construction and refinement of a high speed PS-OCT system by using a rapid scan optical delay line. In the second year, a transgenic mouse model will be used in conjunction with PS-OCT to study multistage melanoma carcinogenesis and differentiation of benign and 1 malignant lesions. This transgenic mouse model uses tyrosinase promoter to target expression of the mutated human T24 Ha-ras oncogene, as previously developed by Dr. Powell who will serve as a consultant in the second year. The overall goals of developing a system capable of determining benign from malignant pigmented lesions will be achieved through the following specific aims: (1) develop PS-
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OCT instrumentation, (2) compare PS-OCT and histology to differentiate benign from malignant lesions. Successful completion of this pilot project will further the development of a practical and inexpensive device that can be used to differentiate benign from malignant lesions of the skin. Thus this research will have the potential to improve patient care and reduce the human and economical cost of melanoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POLYAMINES AND CHEMICAL CARCINOGENESIS Principal Investigator & Institution: O'brien, Thomas G.; Senior Investigator; Lankenau Institute for Medical Research Wynnewood, PA 19096 Timing: Fiscal Year 2003; Project Start 01-JUL-1981; Project End 31-JUL-2008 Summary: (provided by applicant): This is a very opportune time to study the genetic basis of complex phenotypes such as susceptibility to cancer. There are undoubtedly many genes that contribute to this phenotype and discovering their identities should lead to advances in cancer diagnosis, prevention, and even treatment. The mouse has always been the best experimental system for genetic analysis of complex mammalian traits, and with the sequencing of the mouse genome the utility of mouse models for identification of the genes at cancer susceptibility/resistance loci is further enhanced. Using a transgenic mouse model, we have previously demonstrated that the ornithine decarboxylase (Ode) gene is a susceptibility gene for nonmelanoma skin cancer in the mouse. When Odc is overexpressed in the target cells for carcinogens in skin, a previously resistant mouse strain becomes highly sensitive to skin tumorigenesis. Despite the strong effect of Odc on susceptibility, this phenotype can be modified by genetic loci present in a variety of inbred mouse strains. Published and ongoing genetic mapping studies have identified two classes of modifier loci, those that affect total tumor multiplicity and those that affect predisposition to squamous cell carcinoma development. The genes present at these loci presumably function in important effector pathways that: (a) are relevant to the tumor development process and (b) sensitive to changes in intracellular polyamine levels caused by Odc overexpression. In this proposal, we will focus our attention on fine mapping of these modifier loci, identifying the genes at these loci, and developing new models to study the genes' function in vivo. The specific objectives are to: (1) Fine map and identify the gene at Moo1 a strong modifier of tumor multiplicity on chromosome 17; (2) Map an X-linked modifier locus in crosses involving the C57BL/6J and BALB/cJ strains; (3) Fine map and identify the gene at Moo2, a strong modifier of tumor multiplicity on chromosome 6; (4) Develop novel mouse models in which an important regulatory region of the human ODC gene is knocked in to the homologous region of the mouse gene. Common allelic variants of modifier genes undoubtedly contribute greatly to the differences between individuals in human cancer susceptibility. Identifying such genes through research on human populations is extremely difficult, but utilizing genetic analysis in the mouse to identify mouse modifier genes is now quite feasible. In the very near future, it should be possible to test hypotheses about human cancer modifier genes using results derived from mouse models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PREVENTION OF PHOTOCARCINOGENESIS BY ANTIOXIDANT Principal Investigator & Institution: Katiyar, Santosh K.; Assistant Professor; Dermatology; University of Alabama at Birmingham Uab Station Birmingham, AL 35294
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Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant)Chronic exposure to solar ultraviolet (UV) radiation, particularly UVB (290-320 nm), is primarily responsible for more than 1,000,000 new cases of nonmelanoma skin cancer each year in the USA alone, making it the most hazardous environmental carcinogen known for humans. Thus, there is an urgent need to develop strategies to prevent the occurrence of cutaneous malignancies. It is well documented that UV radiation is a potent producer of reactive oxygen species (ROS), which play a critical role in cellular signal transduction pathways. Phosphorylation of cell signaling molecules is implicated in various skin diseases including skin cancer. One approach to reduce the risk of UV-induced ROS-mediated skin cancer is the use of antioxidant agents. Several studies led to a strong suggestion that the regular intake of polyphenolic antioxidants from green tea may be an appropriate and effective strategy to prevent some forms of human cancers. We and others have shown that a potyphenolic fraction isolated from green tea, and particularly its major and the most effective chemopreventive antioxidant constituent (-)-epigallocatechin-3-gallate (EGCG) has remarkable preventive effects against UV-induced skin carcinogenesis in mouse model. We found that treatment with EGCG to human skin before UV exposure inhibits UV-induced oxidative stress. The aim of this application is to defme the mechanism through which EGCG would prevent UV-induced oxidative stress-mediated cell signaling pathways in human skin. The central hypothesis to be tested in this proposal is that UV-induced oxidative stress causes phosphorylation of epidermal growth factor receptor (EGFR), and mitogen-activated protein kinases (MAPK), such as extracellular signal-regulated kinase (ERK1/2) and p38 in human skin. The corollary to our hypothesis is that topical treatment with EGCG before UV exposure of the skin will prevent UV radiation-induced oxidative stress, which in turn will inhibit oxidative stress-mediated phosphorylation of cellular signaling events. The inhibition of UVinduced oxidative stress- mediated signaling pathways by EGCG will prevent the occurrence of skin cancer. Validation of this hypothesis would have major implications for the importance of oxidative stress-mediated skin cancer, as well as offering promise for the development of novel intervention approaches to mitigate UV-induced cellular signaling events linked to skin cancer incidence by the use of antioxidants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREVENTION OF SKIN CANCER BY SCUTELLARIA BAICALENSIS Principal Investigator & Institution: Wei, Huachen; Associate Professor/Director; Dermatology; Mount Sinai School of Medicine of Nyu of New York University New York, NY 10029 Timing: Fiscal Year 2001; Project Start 18-SEP-2000; Project End 30-JUN-2005 Summary: Chinese herbal medicine Huang Qin (Scutellaria baicalensis) has a variety of anti-inflammatory and anti-cancer activities. The central hypothesis of this proposal is that Scutellaria baicalensis extracts (SBE) inhibit ultraviolet (UV) B-induced pyrimidine dimers and oxidative DNA damage, and modulate UVB-activated signal transduction cascades and inflammatory responses, thereby suppressing the initiation and promotion of photocarcinogenesis. The initial aim of the project is to determine if pre- or postapplication of SBE prevents UVB-induced skin carcinogenesis. The initial aim of the project is to determine if pre- or post-application of SBE prevents UVB-induced skin carcinogenesis. SBE will be topically applied to hairless mice during exposure to UVB. The protective effect will be evaluated by analyzing the latency period, tumor incidence and multiplicity. The second aim is to evaluated the effects of SBE on the initiation, promotion, and progression of photocarcinogenesis. A combined UVB-carcinogen
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model will be used to dissect the anti-initiational or anti-promotional effects of SBE on UBV- induced skin carcinogenesis. SBE will be topically applied to mouse skin before an initiating dose of UVB, followed by TPA promotion, or applied before UCB radiation in DMBA-initiated mice. The therapeutic effect of SBE will be tested on the existing cutaneous tumors by recording the tumor regression rate and malignant conversion rate. The third aim is to determine if SBE modifies UVB-induced intermediate endpoints relevant to initiation and promotion, e.g. DNA photoproducts, oxidative DNA damage, inflammatory responses, protooncogene expression and activation of AP-1 factor in vivo and in vitro. Lastly, we will further evaluate the efficacy of SBE in protection of UVBinduced erythema and discomfort in human skin. The molecular markers of DNA damage (pyrimidine dimers and 8-OHdG), apoptosis (p53 protein expression), and cell proliferation (PCNA) will be determined in the human skin biopsies as well as in 3dimensional reconstituted human skin chronically exposed to UVB. Successful completion of the proposed studies will not only contribute to innovative use of herbal extracts as preventive and/or therapeutic agents against human skin cancer, but also promote the research on the anti-cancer action of BE in other human malignancies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROBING SUNSCREEN FAILURE THROUGH ENERGY TRANSFER TO DNA Principal Investigator & Institution: Nordlund, Thomas M.; Physics; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2004 Summary: (provided by applicant): The aim of this project is to determine if sunscreens can fail to protect against UV damage by transferring absorbed UV energy to DNA. This project has three immediate goals (I) measure the interaction of sunscreen agents (e.g, octyl methoxycinnamate) with DNA through fluorescence and absorption spectroscopy; (ii) select the most favorable fluorescent DNA base analog- 2-aminopurine (2AP), or one of the pteridine-nucleoside analogs ("PNA's", M. Hawkins, Pediatric Branch, NCI)-to act as an energy acceptor from sunscreen; (iii) measure the efficiency of UV-excited energy transfer from active sunscreen agents to DNA and from DNA to sunscreen. In support of these goals, study of the dependence of energy transfer in DNA as a function of DNA length and conformation must continue. Sunscreens efficiently absorb UV radiation which can cause DNA damage in skin. The most favorable disposal mechanism for this absorbed energy is molecular internal conversion, leading to harmless heat dissipation. Studies of unfavorable energy-disposal mechanisms (e.g., radical and singlet oxygen formation) have been done to determine whether these processes, though rare, may contribute to DNA damage and the (bottom-line) failure of sunscreens to reduce the incidence of skin cancer in society. We will measure energy transfer, also an energydissipation mechanism, between sunscreen agents and DNA under in vitro conditions to determine the efficiency of transfer. Sunscreen agents can quickly be screened for unfavorable interaction with DNA, once protocols have been optimized. The next step would be to determine whether the in vitro interaction between sunscreen and DNA occurs in vivo. We have described 2AP-sensed base-to-base energy transfer in DNA in detail and, more recently, measured spectra of PNA-DNA from the Hawkins group. Neighboring bases (esp. adenine), base stacking, double helix formation and other DNA interactions cause spectroscopic changes that can be measured with commonly available absorption and fluorescence spectrophotometers. Spectral shift analysis (previously developed) as a function of temperature and solvent properties, as well as time-resolved fluorescence measurements will be performed to obtain native DNA spectroscopic
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signatures. Changes upon addition of sunscreen can then be precisely measured and the efficiency of energy transfer (or other interaction) determined (Xu and Nordlund, 2000). DNA damage would be directly proportional to this efficiency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROSTOGLANDINS AND UVB CARCINOGENESIS Principal Investigator & Institution: Oberyszyn, Tatiana M.; Assistant Professor; Medical Microbiol & Immunology; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, OH 43210 Timing: Fiscal Year 2001; Project Start 14-AUG-1998; Project End 31-JUL-2003 Summary: The skin has historically been considered to function as a barrier against chemical or physical insults from the external environment. In addition to these barrier functions, the skin is now recognized to be an organ with important immunological and biochemical functions that can impact the health of the entire organism. Ultraviolet B radiation (UVB, 290-320nm) is responsible for the majority of cutaneous damage following both acute and long term exposure and is believed to be the single most important etiologic agent in human skin cancer. UVB carcinogenesis has recently been associated with an inflammatory response that includes the production and release of prostaglandins, which may be critical to the observed damaging effects of UVB on skin, which include the formation of oxidative DNA adducts. The underlying Hypothesis for the proposed studies is that there is a link between selective induction of one of the isoforms of the gene responsible for prostaglandin production, i.e. cyclooxygenase-2 (COX-2), and the resulting formation of oxidative DNA damage within the cutaneous microenvironment which ultimately results in the epigenetic and genetic alterations observed during UVB induced mutagenesis and carcinogenesis. Studies in the first specific aim will take advantage of the development of knock-out mice that do not contain either the constitutive isoform of the COG gene, COX-1 or mice which are COX2 null. These studies will determine the critical nature of the presence of prostaglandins derived from these genes on the formation of DNA adducts, the induction of focal p53 clustering within the hyperplastic skin and to the kinetics of development and growth of UVB- induced papillomas and carcinomas. Studies in specific aim 2 will examine the ability of NSAIDS, specific inhibitors of the cyclooxygenase isoforms including, NS-398 and indomethacin, to prevent UV induced tumor growth. These studies offer a unique opportunity to gain insight into the role that COX-1 and COX-2 derived prostaglandins play in UV induced squamous cell carcinoma development and provide a potentially important pharmacological approach to abrogate or inhibit the deleterious effects of UVB exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROTEIN KINASE C SIGNALING IN APOPTOSIS AND SKIN CANCER Principal Investigator & Institution: Denning, Mitchell; Ob, Gyn, and Reproductive Med; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, IL 60611 Timing: Fiscal Year 2001; Project Start 20-DEC-1999; Project End 30-NOV-2004 Summary: Ultraviolet (UV) radiation from the sun is the main causative agent in the formation of non-melanoma skin cancer, already the most frequent type of cancer in the United States. In addition, the risk for exposure to harmful UVB radiation is rising with the continued destruction of the protective atmospheric ozone layer. The induction of programmed cell death, or apoptosis, is a major cellular protective mechanism for
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keratinocytes exposed to mutagenic doses of UV radiation. Indeed, inhibition of apoptosis by expressing cell survival genes or inactivation of tumor suppressor genes enhances skin tumor formation. A long term goal of this proposal is to elucidate the signal transduction pathways activated by UV radiation which trigger apoptosis, and how these death effector pathways become altered during multi-stage skin carcinogenesis. Induction of apoptosis by UV radiation involves activation of protein kinase C (PKC) delta, however PKCdelta is often inactivated or down-regulated in neoplastic keratinocytes. To determine the role of PKCdelta in the apoptotic response and malignant transformation of human keratinocytes exposed to UV radiation, we propose to 1) Characterize the distribution of PKCdelta in normal skin and skin tumors, and determine the activation sate of PKCdelta in cultured normal keratinocytes and squamous cell carcinoma cell lines; 2) Characterize the mechanisms by which PKCdelta activation triggers keratinocyte apoptosis by establishing keratinocyte cell lines with inducible expression of activated PKCdelta and analyzing their apoptotic phenotype; 3) Dissect the specific roles of PKCdelta activation in UV radiation-induced apoptosis by analyzing the induction of apoptosis by UV radiation in keratinocytes expressing a dominant/negative PKCdelta; and 4) Determine the effects of PKCdelta inactivation on keratinocyte transformation using in vitro and in vivo transformation assays of keratinocytes which have survived UV irradiation. These studies will help define the molecular mechanisms involved in skin carcinogenesis by UV radiation, and may identify molecular targets for preventive or therapeutic interventions. These studies will also enhance our understanding of basic apoptotic signaling pathways relevant to many normal and disease processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION AND INDUCTION OF APOPTOSIS IN SKIN CANCER Principal Investigator & Institution: Mcdonnell, Timothy J.; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2001 Summary: Non-melanoma skin cancers (NMSC) are the most common malignancies in the United States. These malignancies vary from indolent lesions to those which are clinically aggressive. At present the molecular biologic correlates predictive of clinical aggressiveness are poorly characterized. Patients with these cancers are most often treated surgically. However, some patients require non-surgical intervention. Systemic interferon-alpha (IFN) plus 13 cis-retinoic acid (RA) is effective in the treatment of these patients. However, it is not possible to determine a priori which patients will benefit from this therapy. A reasonable hypothesis is that cell death deregulation contributes to the development of these tumors. This hypothesis provides the conceptual framework for examining the molecular genetic alterations commonly associated with NMSC in the context of cell death regulation. In fact, the most common mutations in NMSC occur in genes known to regulate cell death, p53 and Ha=-ras. Additionally, we have recently shown high levels of bcl-2 expression in certain types of NMSC. Our preliminary studies also suggest that altered expression of bax and bcl-x may contribute to the pathogenesis of NMSC. Tissue samples will be obtained from patients receiving protocol IFN plus RA and/or surgical treatment at the University of Texas M.D. Anderson Cancer Center. Samples will be assessed for expression of bcl-2 and related gene family members known to regulate cell death including bcl-x and bax using Western blotting and immunohistochemistry. In addition, the apoptotic index will be directly assessed using in situ labeling techniques. The results will be correlated with clinical pathologic parameters and patient response to therapy. The effects of apoptosis deregulation on the
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development of skin cancer will be studied prospectively in a transgenic mouse model that has been established using a keratin promoter-bcl-2 cDNA minigene (HK1-bcl-2). The HK1-bcl-2 mice will be examined for the effects of bcl-2 overexpression on epidermal differentiation by using immunofluorescence techniques for specific differentiation markers. Transgenic mice will be observed for spontaneous development of cutaneous neoplasms. These mice will also be treated topically with DMBA followed by serial applications of TPA as well as tested for susceptibility for UV induced skin carcinogenesis. Collaborative genetic complementation studies will assess the ability of overexpressed bcl-2 to cooperate with Ha-ras during in vivo skin carcinogenesis using HK1-ras transgenic mice. Finally, a series of established murine and human squamous cell skin cancer cell lines will be used to examine the influence of specific molecular genetic events on susceptibility to apoptosis induction by IFN and RA. These studies are intended to lead to a better understanding of the biologic basis of NMSC and to facilitate the transfer of the translational implications of these studies to the clinical setting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RETINOID PROGRESSION
RECEPTOR
FUNCTION
IN
SKIN
CANCER
Principal Investigator & Institution: Clifford, John L.; Cancer Prevention and Control; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 01-JUL-1998; Project End 03-JUN-2003 Summary: Squamous cell carcinoma (SCC) is the most clinically aggressive form of nonmelanoma skin cancer and in spite of aggressive treatment, deeply invasive SCC lesions recur at a high rate (30 percent). Therefore there is an urgent need for the development of improved therapeutic and preventive treatments for this disease. Retinoids are important modulators of epithelial differentiation and proliferation. Retinoids are effective in the treatment and prevention of epithelial cancers, including cutaneous SCC. However the mechanism for this effect is not well understood. In order to better design chemopreventive therapies for cutaneous SCC, more information about the mechanism of retinoid action in this system is needed. Retinoids exert their effects primarily through nuclear receptors, retinoic acid receptors (RARalpha, beta and gamma) and retinoid X receptors (RXRalpha, beta and gamma), members of the steroid hormone receptor superfamily. Retinoid receptor loss has been correlated with malignancy in several systems, and one recent study has demonstrated a suppression of RARalpha, RARgamma and RXRalpha expression in SCCs of patients. This study is based on the hypothesis that retinoid receptor loss contributes to the malignant phenotype by rendering epithelial cells resistant to retinoids, which wold normally suppress carcinogenesis. To test this hypothesis, HaCaT cells, a spontaneously immortalized, nontumorigenic, keratinocyte- derived cell line was chose. These cells express the two predominant retinoid receptors normally found in skin, RARgamma and RXRalpha, and retain the same differentiation characteristics and response to retinoids as normal keratinocytes. The HaCaT cells, which are a model for premalignant cells, will be used to accomplish the following specific aims: 1.) To create RARgamma null, RXTalpha null and RARgamma/RXRalpha double null cells by homologous recombination-mediated gene targeting. 2.) To determine whether loss of receptor expression results in an altered cell phenotype, specifically with regard to tumorigenic potential, differentiation capacity and response to alterations in retinoic acid (RA) levels. 3.) To reexpress the missing receptor (RARgamma or RXRalpha) in the knockout cell lines by stable transfection in order to determine whether the putative phenotype observed is the direct result of the genetic lesion. A somatic cell gene targeting approach has been successfully by the
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principle investigator to analyze retinoid receptor function in F9 embryonal carcinoma cells. It is expected that the generation of receptor null HaCaT cells will provide an equally powerful tool for understanding the role of retinoid receptors in the development of cutaneous SCC, as well as their role in epidermal differentiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE CARCINOGENESIS
OF
P53
IN
UV
IMMUNE
SUPPRESSION
AND
Principal Investigator & Institution: Kripke, Margaret L.; Executive Vice President and Chief Acade; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030 Timing: Fiscal Year 2001 Summary: Skin cancers induced in inbred mice by chronic UN irradiation are highly antigenic and exhibit a high frequency of p53 mutations. In this model, cancer induction by UV radiation is accompanied by suppression of the immune response against these skin cancers, and the immune suppression plays an essential role in skin cancer growth and pathogenesis. Recent studies indicate the UV-induced DNA damage is the primary event that initiates immunosuppression. Because p53 plays a pivotal role in the response to and repair of DNA damage, this gene may serve as an essential control point in the pathway leading to UV-induced immune suppression, in addition to playing a role in the process of neoplastic transformation. Furthermore, mutant p53 protein could contribute to the unusual antigenic properties exhibited by UV-induced tumors. To test these hypotheses, p 53 knock out mice, in which one or both copies of th p53 gene have been inactivated by homologous recombination, will be exposed to UV radiation and tested for susceptibility to UV-induced suppression of cell-mediated immunity and induction of immunosuppressive epidermal cytokines. The role of p53 in UV carcinogenesis will be assessed by comparing tumor induction in +/+, +/-, and -/- mice on a C57BL/6 genetic background. To determine whether mutant p53 protein serves as a transplantation antigen on UV-induced tumors, the antigenic properties of tumors induced in +/+, +/-, and -/- mice will be compared. If athe tumors induced in p53 null mice do not express UV-associated tumor antigens, these tumors will be used as recipients for transfection of mutated p53, to determine whether introduction and expression of mutated p53 confers on these cells the unusual antigenic characteristics of UV-induced skin cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF PKC IN TUMOR PROMOTION Principal Investigator & Institution: Verma, Ajit K.; Professor; Human Oncology; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2002; Project Start 01-JUL-1983; Project End 28-FEB-2007 Summary: The objectives of this proposal are to determine the distinct roles that protein kinase C (PKC) isoforms (delta and epsilon) play in multistage (initiation, promotion and progression) mouse skin carcinogenesis. Knowledge obtained will contribute to the management of human squamous cell carcinoma (SCC), a predominant nonmelanoma metastatic human skin cancer. PKC, a phospholipid-dependent protein kinase, is a major intracellular receptor for the tumor promoter phorbol ester TPA. PKC represents a family of eleven isozymes (alpha, betaI, betaII, gamma, delta, epsilon, sigma, eta, theta, lambda, and mu), and six of these PKC isoforms (alpha, delta, epsilon, eta, sigma and mu) are expressed in mouse epidermis. To determine the in vivo functional specificity of
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PKC isoforms in mouse skin carcinogenesis, we have generated transgenic FVB/N mouse lines that overexpress epitope tagged PKCalpha, PKCdelta or PKCepsilon isozyme in epidermis under the control of the human keratin 14 promoter. Since PKC is the key receptor for TPA, the DMBA-TPA protocol was used to induce skin tumors to investigate PKC isoform specificity in these transgenic mice. We found that PKCalpha overexpression had no effect on skin tumor promotion by TPA, PKCS overexpression suppressed the formation of both papilloma and SCC while PKCE overexpression induced metastatic SCC formation independently of prior papilloma development. Based on these observations, we plan to test two hypotheses: 1) PKCdelta and PKCepsilon expression levels determine skin tumor formation susceptibility as the result of modulation of specific steps of mouse skin carcinogenesis (e.g., initiation, promotion and/or progression). 2) Skin tumor suppression in PKCdelta transgenic mice and development of metastatic SCC in PKCepsilon transgenic mice are associated with the altered expression of specific genes and proteins leading to an imbalance within normal cell proliferation, differentiation and apoptosis. We propose the following specific aims to test the hypotheses: Specific Aim #1. To determine, using several mouse models (transgenic and knockout), whether PKCdelta or PKCepsilon expression level determines susceptibility to skin tumor formation. Specific Aim #2. To determine, using PKC-inducible transgenic mice, whether tumor suppression in PKCdelta and carcinoma development in PKCepsilon transgenic mice are the results of the effects of transgene overexpression on the initiation, promotion and/or progression stage of carcinogenesis. Specific Aim #3. To find clues about the mechanisms associated with the opposing effects of PKCdelta and PKCepsilon, on mouse skin carcinogenesis by analysis of gene expression using the cDNA expression array. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF SURVIVIN IN NONMELANOMA SKIN CANCER Principal Investigator & Institution: Grossman, Douglas; Dermatology; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): The long-term goal of this project is to understand how apoptosis influences the development of non-melanoma skin cancer. Keratinocyte apoptosis mediated by p53 is thought to represent an important defense against cutaneous squamous cell carcinoma (SCC), although the role of apoptosis resistance in tumor development has not been well established. Our initial work has focused on survivin, a newly identified apoptosis inhibitor, that is absent in normal keratinocytes but expressed in SCC and precursor lesions. Our hypothesis is that survivin expression is important in the development of SCC. To investigate the role of survivin in skin carcinogenesis, we have generated a transgenic mouse (K14-survivin) expressing survivin in the skin. Before moving to molecular analyses of survivin function in skin cancer, we will first use this transgenic system to investigate the role of survivin in wellcharacterized models of skin tumor formation. Preliminary studies suggest that survivin expression may oppose the p53-apoptotic pathway in keratinocytes, and is important for preventing papilloma regression and promoting progression to SCC. First, we will determine if survivin expression combined with loss of p53 enhances SCC formation by subjecting K14-survivin mice on a p53+/- background to chemical carcinogenesis. Second, we will examine whether survivin expression controls tumor formation at the level of papilloma regression, and if it can serve as a tumor initiator or promoter in this system. Third, the effect of transgenic survivin expression on ultraviolet-B (UVB)induced tumor formation will be investigated using K14-survivin mice on a hairless
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background. Finally, we will explore a mechanistic basis for the effect of transgenic survivin on UVB-induced carcinogenesis by correlating tumor formation and regression with the development and growth of p53-mutated keratinocyte clones. These proposed studies promise to elucidate the role of survivin in the development of SCC, and validate this molecule as a potential new therapeutic target in skin cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF THE PPARB IN EPITHELIAL CELL PROLIFERATION 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 2001; Project Start 15-JUN-2001; Project End 31-MAY-2005 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 PPARI3 have remained elusive. Despite numerous roles elucidated for the PPARa and PPARy that contribute to diseases including hyperlipidemias, atherosclerosis, obesity, diabetes and cancer, the function of PPARb has remained a mystery. The recent phenotypical description of a PPARb-null mouse has provided the first direct, in vivo evidence that the PPARb is involved in epithelial cell proliferation. Topical application of the tumor promoter TPA causes enhanced epidermal cell proliferation in PPARb-null mice compared to controls suggesting that the hyperplastic response induced by TPA is attenuated by the PPARb. Further, the non-steroidal anti-inflammatory drug (NSAID), sulindac, inhibits TPA-induced inflammation and epidermal hyperplasia in wild-type mice and this effect is not found in similarly treated PPARb-null mice. This suggests that the beneficial effects of sulindac are modulated by the PPARb. The overall hypothesis of this proposal is that the PPARb3 is central to the epithelial cell proliferative response that results in skin tumor formation from genetic or chemical factors. A secondary hypothesis is that PPARb-null mice will be refractory to the influence of sulindac in preventing epidermal hyperplasia that contributes to skin tumor formation. The first specific aim is to develop three model systems to test these hypotheses. The first model will utilize crossing the PPARb-null mice with patched +1/- mice that are genetically more sensitive to ultraviolet or ionizing radiation-induced skin tumors. The second model will assess two-stage carcinogenicity in the PPARb-null mouse and the last model will characterize a keratinocyte culture system using cells from PPARb-null mice so that it can be utilized to further mechanistically define the role of the PPARb in the TPAinduced epidermal cell proliferative response. Since preliminary data indicate that PPARb attenuates TPA-induced COX-2 mRNA expression, the second specific aim will determine if PPARb-specific alterations in eicosanoid function contribute to the mechanisms of enhanced epidermal cell proliferation. The third specific aim will identify and initially characterize PPARbdependent gene expression in skin cells resulting from treatment with TPA. Results from this work will determine if PPARb influences epidermal cell proliferation that contribute to the incidence of skin cancer, determine if PPARb-dependent alterations in eicosanoid metabolism underlie enhanced cell proliferation induced by TPA in PPARb-null mice, and characterize PPARb target genes in epithelial cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SELENIUM--ANTIOXIDANT OR PROOXIDANT MECHANISM Principal Investigator & Institution: Pence, Barbara C.; Professor & Associate Vice President For; Pathology; Texas Tech University Health Scis Center Health Sciences Center Lubbock, TX 79430 Timing: Fiscal Year 2001; Project Start 10-DEC-1997; Project End 30-NOV-2003 Summary: (Applicant's Abstract) Non-melanoma skin cancer is an increasingly prevalent disease. One out of every six Americans will develop skin cancer in his or her lifetime, and over 700,000 new cases of skin cancer will be diagnosed in the United States this year. Selenium (Se) is an essential trace element with a Recommended Dietary Allowance of 70 ug/day for male adults. Low plasma Se levels have been linked to increased risk of non-melanoma skin cancer and baseline Se levels may be predictive of future skin cancer risk. A recent intervention trial in human skin cancer patients demonstrated no efficacy of selenomethionine against the recurrence of basal cell and squamous cell carcinomas, although there was a decrease in incidence of lung, colon and prostate cancers. However, previous work from the applicant's laboratory has demonstrated a protective effect of Se as selenite for ultraviolet light B (UVB)-induced skin tumors and protection against the UVB-induction of oxidative lesions in the DNA of cultured keratinocytes. The hypothesis to be tested in this application is that the efficacy of Se chemoprevention is dependent on the form of Se used, and this efficacy is determined by the relative contribution of the compound to Se's antioxidant or prooxidant properties. To test this hypothesis, the applicant plans to 1) determine the relative efficacy of selenium compounds to induce the antioxidant pathway by glutathione peroxidase, and also the ability to induce the prooxidant, apoptotic pathway in cultured human keratinocytes and squamous cell carcinoma cells; 2) to determine if there is an interaction between Se compounds and glutathione and other antioxidant compounds; 3) to determine if the antioxidant and prooxidant effects seen in vitro also occur in vivo in the mouse model of skin cancer; and 4) to determine if there are differing chemoprevention capabilities based upon the hypothesized prooxidant mechanisms in a mouse model of skin cancer; and 5) to delineate the molecular mechanisms for the efficacy of Se compounds in skin cancer prevention based on the timing of p53 mutations and their modulation by different Se compounds. The applicant hopes to understand from these experiments which Se compound will be most effective, when and why, in terms of non-melanoma skin cancer prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SKIN CANCER AND YOUTH--AN UNDECLARED EPIDEMIC Principal Investigator & Institution: Allen, Roberta M.; Individual Monitoring Sys, Inc. (Im Sys) 1055 Taylor Ave, Ste 300 Baltimore, MD 21286 Timing: Fiscal Year 2001; Project Start 16-MAR-1998; Project End 30-APR-2003 Summary: The American Academy of Dermatology has proclaimed Skin Cancer an "undeclared epidemic." It is the most prevalent form of cancer, and the one increasing most in incidence and morbidity. The Academy states that 80% of the cumulative damage to the skin takes place by age 18. Despite this alarming situation, young people in America, believing that skin color from the sun is healthy, sexy and cool, are not covering up or coming in from the sun. This project plans to produce and field test 4 video based educational interventions which dramatize the risks of solar overexposure and age-appropriate protective techniques. The Phase II testing will include a pre- posttest format. After the summer following the initial testing, a longitudinal study will be conducted to assess the sustainable pro-heath effects of the intervention. Innovation
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include: high-interest, high-impact video-based dramatizations that are culturally sensitive and age-appropriate, dealing with vital skin cancer issues for which very few other products exist; creation of skin cancer testing instruments for various age levels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SKIN CANCER CHEMOPREVENTION Principal Investigator & Institution: Bickers, David R.; Carl Truman Nelson Professor/Chair; 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-2002 Summary: (Applicant's Description) Non-melanoma skin cancer (NMSC) is the most common type of human cancer and epidemiological evidence strongly implicates ultraviolet radiation in sunlight as the major cause of this form of malignancy. The most common type of NMSC is basal cell carcinoma (BCC) and there are two major types of BCC, those occurring sporadically and those that develop in patients with the genetic disorder known as the basal cell nevus syndrome (BCNS). Sun exposure is a crucial factor in the development of BCC in both populations and recent studies have shown that mutations in the human homologue of the Drosophila segment polarity gene PATCHED (PTC) occur in patients with BCNS and in patients with sporadic BCCs. In this project we plan to conduct a series of studies in SKH-l hairless mice, in patched gene knockout mice (ptc +/-) and in human volunteers to test the hypothesis that systemic administration of the chemopreventive agents, Polyphenone E, a mixture of constituents of green tea, Sulindac, an inhibitor of cyclooxygenase (COX) I and 2 and Celecoxib, an inhibitor of COX 2 can diminish the phototoxic response to ultraviolet B (UVB) and psoralen-ultraviolet A (PUVA) in the skin. Minimal erythema dose (MED) to UVB and minimum phototoxic dose (MPD) to PUVA will be employed to induce a localized phototoxic response in the skin of the animals and the human subjects and the ability of the systemically administered chemopreventive agents to protect against these responses determined. Surrogate biological markers of cancer risk including erythema and edema, apoptosis, c-jun, c-fos and ras p21 induction, BrUdr incorporation, proliferating cell nuclear antigen (PCNA) expression and epidermal growth factor (FGFR) phosphorylation will be assessed. Tumor studies in the animals will permit direct comparison of the susceptibility of the mouse strains to UVB induced tumors and the ability of the chemopreventive agents to reduce the risk of cancer. These studies are closely integrated with those in Projects 1 and 2 and will generate strong supportive data that can be correlated with the findings from those studies. This combined approach has the unique potential to more frilly define the anticarcinogenic effects of selected chemopreventive agents in human populations and to further characterize their mechanism of action. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SKIN CANCER PREVENTION IN A PEDIATRIC POPULATION Principal Investigator & Institution: Crane, Lori A.; Associate Professor; Preventive Med and Biometrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2003; Project Start 15-SEP-1997; Project End 31-MAY-2007 Summary: (provided by applicant): About 1 in 90 American children born in the late 1990's will develop malignant melanoma in their lifetimes. Sun exposure in childhood appears to be the most important preventable risk factor for this disease. This study will
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continue to follow a previously enrolled cohort (n=728) that participated in a randomized trial of a provider-delivered sun protection intervention while children were between the ages of 0 and 3 years. The study will also enroll an additional 900 children who are part of the same birth cohort from 1998. Subjects in both the original cohort and new cohort will be randomly assigned to intervention and control groups; the intervention group will receive a series of tailored newsletters aimed at increasing sun protection over a 3-year intervention period. This tailored intervention is based on the Precaution Adoption Process Model, which focuses on increasing personal perceptions of risk. The effectiveness of the intervention in increasing sun protection of children will be evaluated through telephone surveys of parents at four time-points (upon enrollment and 1, 2, and 3 years later), and through skin exams of all children at the same time-points. Skin exams will provide objective measures of sun exposure using spectrophotometry, assessment of freckling, and enumeration of moles (nevi). This evaluation will assess the long-term effectiveness of the previous provider delivered intervention, the effectiveness of the tailored intervention as a "booster" to the provider intervention, and the effectiveness of the tailored intervention alone. The study also includes a longitudinal study of mole development, which will assess the relationships between sun exposure, "host traits" (such as skin, hair, and eye color, tendency to burn vs. tan, tendency to freckle), and development of nevi, the strongest predictor for malignant melanoma. The study also includes a cost analysis, which will focus on the costs associated with intervention delivery, behavior change, and mole avoidance. If this intervention proves to be effective in increasing sun protection of children, cost and efficiency will be key factors in dissemination and adoption of the intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SKIN CANCER PREVENTION IN NH MIDDLE SCHOOLS Principal Investigator & Institution: Olson, Ardis L.; Associate Professor of Pediatrics; Community and Family Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, NH 03755 Timing: Fiscal Year 2001; Project Start 21-MAR-2001; Project End 31-JUL-2004 Summary: Reducing ultraviolet light exposure in children and adolescents is a primary prevention approach to reducing the incidence of skin cancer. A multi-component community based intervention, "SunSafe," has been shown to be effective at improving the solar protection behaviors of children 2-9 years of age. Older children and adolescents present different challenges. Children in the middle school years are in transition to adulthood and beginning to establish their own health behaviors influenced by peer, school, community and family. In order to change youth solar protection interventions need to both target their health decisional process and influence peers and their local adult role models to practice and promote solar protection. In this proposal, over 3.5 years, we will: 1) Develop and validate new methodologies to determine youth solar protection behaviors on a same day recall; 2) Utilize same day recall, outdoor observation methods and surveys to assess at baseline early teenage sun protection behaviors and motivational factors; 3) Develop and implement a two year multi-component community-based "SunSafe in the Middle School Years" randomized control intervention to improve solar protection of children in the middle school years; and 4) Assess the impact of this new intervention on the solar protection intentions and observed behaviors of early adolescents in rural New Hampshire communities. The interventions for the middle school students will focus on school, community recreation and beach settings, primary care practices, and parents. The interventions are based on theories that include social influence, psychological factors and cognitive decisional
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factors in adolescence. Student teams will develop peer directed interventions that will complement community level interventions. Specific interventions will be directed at changing the solar protection promotion and self-protection behaviors of sports and community adult role models and counseling by primary care providers. The components of this community-based intervention seek to change local social norms about solar protection as well as influence individual adolescent decisions about solar protection through targeted messages. Evaluation of student sun protection behaviors is based on observation and diaries. The evaluation will also assess intermediate mediating variables in students and change in the health promotion and sun protection behaviors of adult role models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SKIN SELF EXAMINATION FOR EARLY DETECTION OF MELANOMA Principal Investigator & Institution: Weinstock, Martin A.; Professor; Rhode Island Hospital (Providence, Ri) Providence, RI 02903 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 28-FEB-2003 Summary: ABSTRACT=Malignant melanoma is a major public health problem for which early detection is critical. Melanoma incidence and mortality have increased over the past several decades. Prognosis is critically dependent on the depth of the primary lesion at the time of initial surgical excision. Hence, monthly thorough skin examination (SSE) by the general public for the purpose of early detection, before deep invasion, is one promising approach for reducing melanoma mortality which has been promoted with increasing vigor in recent years. However, strategies for increasing the practice of SSE have not been rigorously evaluated, nor have the effects of SSE interventions on health care resource use. The investigators propose to conduct a 3-group randomized trial of interventions for increasing SSE use. The participants will be recruited from primary care physician offices. The experimental interventions tested will include written materials, cues, aids, and a videotape given at baseline and tailored feedback reports at 2 and 6 months. One of the two experimental interventions will include faceto-face counseling at baseline and a follow-up phone call 2 weeks later. The control intervention will include materials and a videotape on healthy dietary habits. Assessments will be conducted at 2, 6, and 12 months after the initial intervention. The primary outcome variable will be performance of at least one SSE during the two months prior to the assessment. The investigators will also assess the number of visits to health care providers for skin problems since the prior assessment, and the procedures performed by the provider because of those skin problems. Upon completion of this project, the investigators will have developed an intervention package suitable for dissemination, and will have evaluated its efficacy in improving performance of SSE, as well as its potential effect on health care resource use. The knowledge and experiment thus gained will aid the continuing efforts to encourage SSE and reduce melanoma mortality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROTECTION
SOCIAL
PYSCHOLOGICAL
INTERVENTIONS
FOR
UV
Principal Investigator & Institution: Mahler, Heike I.; Ctr for Human Info Processing; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007
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Summary: (provided by applicant): In spite of extensive educational programs designed to increase awareness of the relation between sun exposure and skin cancer, the majority of adolescents and young adults continue to report intentional exposure to the sun in order to get a tan. In addition, few young people report using adequate sun protection during incidental exposure, and the use of indoor tanning facilities has increased dramatically over the last 10 years. The primary goal of the proposed project is to examine the efficacy of an attractiveness-based (rather than health-based) approach to changing sun exposure and sun protection behaviors. Specifically, the project will examine the effects of an intervention that utilizes photoaging information and UV detect photographs of participants' faces that reveal the amount of damage they have already sustained. This intervention makes the negative appearance consequences of sun exposure more salient and immediate for participants. There are 7 proposed studies that, together, will build on previous UV intervention studies in a number of important ways. First, this research will be conducted with populations that have seldom been targeted by UV protection interventions, i.e., outdoor workers, regular tanning booth users, and people who are sunbathing at beaches. Second, the research will be conducted in California and Iowa, sites that allow the exploration of the efficacy of the intervention (and theoretical questions of interest) among groups with quite different patterns of UV exposure. Third, objective assessment of behavior change at follow-up sessions will be included (i.e., measurement of skin melanin content using a spectrophotometer), a significant improvement over previous reliance on self-reports of intentions or exposure. Fourth, the use of instant UV detect photography to reveal the underlying skin damage of participants will provide highly personal feedback as part of the intervention. Finally, the proposed studies will test hypotheses derived from social psychological theories (particularly, Social Comparison Theory and the Prototype/Willingness Model) to identify factors that moderate and mediate the efficacy of the intervention. Thus, the studies should provide useful information about process as well as outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SPORE IN SKIN CANCER Principal Investigator & Institution: Herlyn, Meenhard; Professor and Chairman; Wistar Institute Philadelphia, PA 191044268 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 27-SEP-2003 Summary: (provided by applicant): Cancers of the skin investigated in this SPORE include, melanoma, cutaneous T cell lymphoma, and squamous cell carcinoma (SCC) and basal cell carcinomas (BCC). The projects and pilot studies are based on a broad existing infrastructure of active basic and translational research in cancers of the skin. They span the fields of cancer epidemiology, biology, immunology, pathology, and therapy to assess cancer risk, diagnosis and detection, prognosis, treatment, and treatment outcome. Immune surveillance genes are investigated as candidate melanoma susceptibility genes (Project 1). Prognostic models are developed for primary melanoma to better design patients? treatment and follow-up (Project 2). Lymphocyte populations from melanoma patients are analyzed to develop new strategies for passive and active immune therapy (Project 3). Patients with cutaneous T cell lymphoma are evaluated that fail therapy with the cytokine IL-12 (Project 4). A melanoma vaccine is being developed that utilizes new principles in antigen presentation (Project 5). Developmental funds will be made available to increase the number of investigators in translational studies. Pilot studies are designed for melanoma, SCC and BCC for disease diagnosis, detection and therapy. All pilot studies utilize novel technologies and approaches to extend the
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existing infrastructure allowing the group to develop new projects in cancer prevention, diagnosis and therapy. Resource centers provide the investigators with support for all projects. By building on a strong existing infrastructure, which will be further strengthened through this SPORE, the proposed studies are expected to have a major impact on the control of cancers of the skin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SPORE IN SKIN CANCER Principal Investigator & Institution: Kupper, Thomas S.; Professor and Chair; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: In this proposal, we seek to establish a Specialized Program of Research Excellence (SPORE) in Skin Cancer at Harvard University and Brigham and Women's Hospital, within the newly configured Dana Farber Harvard Cancer Center. The DanaFarber Harvard Cancer Center SPORE includes investigators from Harvard Medical School and School of Public Health, as well as the Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Children's Hospital Medical Center, Dana- Farber Cancer Institute, and the Massachusetts General Hospital. These institutions have come together around the theme of translational research in melanoma and cutaneous oncology Five Projects, five Shared Resources (Cores), a Developmental Program, and a Cancer Development Program are proposed. Project 1 will translate epidemiologic findings into the Development of improved risk models for melanoma; once developed, these will be validated across a large patient population. Project 2 employs the power of whole genome transcriptional profiling with the ultimate goal of improving our ability to diagnose and predict the biological course of primary melanoma. Project 3 tests the hypothesis that cutaneous T cell lymphoma is a malignancy of a population of memory T cells that normally performs immunosurveillance of the skin, and seeks to identify new targets for therapy. Projects 4 and 5 are exciting translational clinical trials. In Project 4, two diametrically different dendritic cell vaccination strategies are directly compared, using novel immunological endpoints. In Project 5, biochemotherapeutic approaches are employed to treat metastatic melanoma. Immunologic monitoring will be performed again with the goal of improving therapy for melanoma patients. These five Projects are integrated by five Cores. The Biostatistics Core provides expert consultation to each study while the Tissue and Pathology Core provides controlled and organized access to tissue vital for these projects. An assessment of immunologic endpoints. The Clinical Data Management Core provides a vital service of creating dynamic and flexible databases that integrate Projects across multiple Harvard-affiliated hospitals. Finally, a Development Program features five projects, each of which is a candidate for evolution into a full project is promising translational results are obtained. A Career Development Program, which takes a broad view of the development of the physician scientist over the course of a career, is a centerpiece of this application. An administrative structure is in place that will assure oversight, integration, planning, didactic activities, and most importantly, the growth and evolution into a full project if promising translational results are obtained. A Career Development Program, which takes a broad view of the development of the physician scientist over the course of a career, is a centerpiece of this application. An administrative structure is in place that will assure oversight, integration, planning, didactic activities, and most importantly, the growth and evolution of the SPORE over the next five years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SUN PROTECTION AND SKIN CANCER AWARENESS IN WATERMEN Principal Investigator & Institution: Ehrlich, Alison; Dermatology; George Washington University 2121 I St Nw Washington, DC 20052 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Many attempts have been made to change sun protection and skin cancer awareness in both patients and the general population. However, these efforts have had varied success. Few studies have implemented behavioral theories of individual risk assessment as a component of behavioral intervention. We have developed a behavior intervention questionnaire study in which the intervention will be a composite of skin cancer screening and education. A component of the education will focus on using the "risk as precautions" model to enhance the subject's personal awareness of skin cancer risk. Populations with increased risk of skin cancer will benefit most from this type of intervention. The Maryland Watermen's Association (MWA) represents a population with a known increased risk of occupational induced skin cancer. We will conduct a behavior intervention questionnaire study of licensed Maryland watermen. The study will address the following issues: 1) whether education alone or education and skin cancer screening is an effective tool for changing sun protection behavior in an adult population with occupational exposure; 2) whether skin cancer risk awareness can predict a change in sun protection. This study will provide critical data for subsequent use of the risk as precautions model and skin cancer screening as methods to increase skin cancer awareness and change sun protection behavior in outdoor workers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SUN SAFETY: SKIN CANCER EDUCATION FOR FAMILY CHILD CARE Principal Investigator & Institution: Birney, Amelia J.; Healthmark Multimedia, Llc 1201 Connecticut Ave Nw, #250 Washington, DC 20036 Timing: Fiscal Year 2001; Project Start 14-SEP-2000; Project End 31-AUG-2003 Summary: Most sun exposure occurs before the age of 20 and adoption of protective measures in childhood can reduce the lifetime incidence of skin cancer by 78%. This Phase II SBIR project will result in companion multimedia programs (Sun Safe Central and Adventures with the Shady Characters) in both English and Spanish, targeting home-based child-care providers and the preschool children in their care. The programs will provide Web-based sun protection information and interactive tools for the providers, and a CD-ROM with sun protection games, songs and other activities for children 3-5 years old. In Phase II, we will produce the remaining information, tools and graphic elements to include: 1) expanding the scope of information for providers; 2) adding tools to help providers integrate sun protection policies and practices into their daily routine, and 3) teaching children age-appropriate sun protection behaviors through fun-filled activities. A two-group randomized field test will assess the programs' effectiveness at changing providers' and children's knowledge and practices, as well as providers' self-efficacy regarding implementing sun protection policies and practices for their child-care business. PROPOSED COMMERCIAL APPLICATION: Not Available Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SUNLIGHT RELATED STEPS IN HUMAN SKIN CANCER Principal Investigator & Institution: Brash, Douglas E.; Professor; Therapeutic Radiology; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 01-APR-1992; Project End 31-DEC-2002 Summary: The long-term aim of this project is to understand how sunlight causes skin cancer. Skin is a unique system for revealing early events in cancer because the lesions are observable, the carcinogen is known, and some cancers progress through defined stages. We initially focussed on UV-induced mutations. Now, we are focussing on UVinduced apoptosis and its role in preventing or accelerating sunlight-induced cancer. The working hypothesis is that a key step in developing skin precancers is loss of cellular proofreading. That is, abnormal cells no longer commit suicide. Our previous work generated a model at each of three levels: genes, cell populations, and pharmacologic agents. Genetic model: Apoptosis requires both an abnormality detector, which involves p53, and a cell cycle abnormality signal. Cell population model: A UVinduced p53 mutation renders a cell apoptosis-resistant. Additional UV allows the mutant cell to clonally expand at the expense of its normal neighbors, resulting in a precancer. Pharmacology model: Many drugs affect the abnormality detector or the abnormality signal. The altered apoptosis biases the competition between normal and mutant cell populations, so that these agents act as chemopreventives or tumor promoters. The research in this application uses cultured cells, mouse skin, and human skin to test individual points of these models: i) Does apoptosis- resistance enable a mutant cell to clonally expand to a precancerous lesion? ii) Do the different mutant p53 alleles found in human skin cancers and precancers have different phenotypes for apoptosis versus cell cycle arrest? iii) Do chemopreventive agents and tumor promoters act by influencing UV-induced cellular proofreading? iv) What genes influence UVinduced cellular proofreading? v) How does a DNA photoproduct signal cell cycle arrest or apoptosis? vi) Does p53- mediated clonal expansion clone out single mutant cells already present in sun-damaged skin? These studies could find that: sunlight acts as a tumor promoter by killing unmutated cells; chemoprevention is beneficial only before apoptosis-resistant cells appear; and the genomic location of a DNA photoproduct determines whether cell cycle arrest or apoptosis ensues. The questions addressed here are directly relevant to the health of an increasing number of individuals: skin cancers are now as frequent as all other cancers combined. More broadly, the mechanisms operating in keratinocytes are likely to be a part of cancer development in other cell types as well. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SUNNY DAYS HEALTHY WAYS GRADES 6-8 SUN SAFETY CURRICULUM Principal Investigator & Institution: Buller, David B.; Senior Scientist and Vice President; Amc Cancer Research Center 1600 Pierce St Denver, CO 80214 Timing: Fiscal Year 2001; Project Start 02-SEP-1998; Project End 30-JUN-2002 Summary: U. of Arizona Cancer Center (ACC) and U. of Alabama, Birmingham (UAB) will develop a sun safety curriculum for children in grades 6-8 that contains classroom instruction and interactive multimedia computer programs and evaluate its ability to increase children's sun protection attitudes and behaviors (limit time in sun and use protective clothing, sunscreen, and shade), produce a sun safety norm, and decrease tanning norms in a community trial in public schools. Skin cancer is epidemic. Childhood solar protection could reduce UVR exposure and the risk of skin cancer since
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severe childhood sunburns and intermittent exposure may promote melanoma and basal cell carcinoma and lifetime sun exposure (most occurs in childhood) is associated with squamous cell carcinoma. The curriculum will integrate with the ACC's successful Sunny Days, Healthy Ways grade K-5 sun safety curriculum and build upon a pilot middle school program by UAB. In Phase I (Y1 and Y2), curriculum components will be created for each grade, containing interactive exercises by teachers and interactive multimedia programs utilizing peer models. Social Cognitive Theory and persuasion theories will guide curriculum design. It will focus on outcome and self-efficacy expectations, goal-setting, behavioral skills, self-monitoring, and reinforcements for sun safety. Student and teacher focus groups, an external advisory board, and assessment of school policies and environment will aid curriculum designers. Student surveys will be pilot-tested. The curriculum will be evaluated in Phase II (Y3 and Y4) in a pair-matched randomized pretest-posttest control group community trial, enrolling 15 pairs of schools from five public school districts in AZ, AL, and FL (150+ students tested per school). Process evaluation will monitor implementation and multimedia use. Outcome evaluation will assess changes in attitudes and behaviors, self-efficacy and outcome expectations, and tanning and sun safety norms with a first implementation in the 19992000 academic year and a second implementation in 2000-01. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SUNNY DAYS, HEALTHY WAYS CD-ROM CURRICULUM Principal Investigator & Institution: Buller, Mary K.; President; Partners for Health Systems, Inc. 1650 Pierce St Lakewood, CO 80214 Timing: Fiscal Year 2001; Project Start 15-SEP-1998; Project End 03-JUN-2002 Summary: Skin cancer is epidemic and prevention must start in childhood to reduce lifetime ultraviolet radiation exposure and severe sunburns. Partners for Health Systems, Inc. (PHS) will produce an interactive multimedia (CD- ROM) version of the Sunny Days, Healthy Ways (SDHW) elementary school sun safety curriculum and evaluate its effectiveness at increasing knowledge, changing attitudes favorably, and increasing sun safe behavior. The target population for this Phase II project is students enrolled in grades K through 5 in eight public elementary schools in metro Denver and Greeley, Colorado. Multimedia are increasingly attractive to health educators, teachers, students, and parents. This Phase II project will build upon the grade K and 2 prototypes from Phase I (SBIR #1R43CA76755) to design and produce a complete SDHW multimedia program. The authoring of the CD-ROM multimedia programs will be performed under contract by the AMC Cancer Research Center's Health Communications Core. Agent-based, knowledge-construction interfaces will be programmed into the CD-ROMs to function as intelligent tutors for students. The ability of the CD-ROM SDHW to improve children's sun protection behavior (primary outcome) will be tested in a pair-matched randomized pretest-posttest control group design, employing l2 schools, 144 classes, and 2,160 students. Data analysis will be performed under contract by the AMC Cancer Research Center's Research Methodology and Biometrics Department. PROPOSED COMMERCIAL APPLICATION: Computer use in education is increasing rapidly. The CDC is planning to issue national skin cancer prevention guidelines for inclusion K-12 comprehensive health education. All U.S. schools will be encouraged to incorporate sun safety in their curriculum. Thus, the sun safety CD-ROM curriculum has potential commercial application in public and private elementary schools, preschools, public libraries, as well as the home market, over the Internet, and for worksite wellness and managed care prevention programs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: T CELL DEPENDENT TERMINAL MATURATION OF LANGERHANS CELLS Principal Investigator & Institution: Takashima, Akira; Professor; Dermatology; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001; Project Start 01-JUL-1996; Project End 30-JUN-2006 Summary: (provided by applicant): As a member of the dendritic cell (DC) family, Langerhans cells (LC) play key roles in the induction of T cell-mediated immune responses in skin. During antigen presentation, LC deliver activation signals to T cells and, at the same time, undergo maturational changes. The long-term objectives are to study molecular mechanisms regulating various changes that accompany T celldependent terminal maturation of LC and to develop new immuno-modulatory strategies that are designed to control bi-directional LC-I cell interaction. The specific aims are: 1) To define functional roles played by chemokines and chemokine receptors in LC migration. To test the hypothesis that mature LC can be "entrapped" by an artificial chemokine gradient created in their migratory path and loaded with antigen, ethylene-vinyl-acetate (EVA) polymer particles releasing MIP-3B and OVA (model antigen) will be implanted s.c. in mice. Induction of OVA-specific responses will validate the efficacy of this in situ LC vaccine strategy. To test the second hypothesis that efficacy of DC vaccines can be improved by promoting DC homing, CCR7 DNAtransfected "bullet" DC will be examined for their homing property and the ability to induce anti-tumor protective immunity. 2) To study the expression and function of a novel anti-apoptotic factor (AIM) in antigen presentation. Preliminary results suggest that LC produce a recently identified anti-apoptosis factor AIM during antigen presentation, which, in turn, determines the magnitude and kinetics of cellular immune responses by preventing premature apoptosis of LC and I cells. These hypotheses will be tested at cellular and animal levels using anti-AIM mAb, recombinant AIM, AIMdeficient mice, AIM-transgenic mice, and AIM cDNA-transduced "super" DC. 3) To determine the molecular identity and functional roles of ecto-ATPase and ADPase activities on LC. Preliminary results suggest that CD39 is responsible for ecto-ATPase and ADPase activities on LC and that LC-associated CD39 plays dual functions, i.e., a protective role against chemically induced skin inflammation and an immunoregulatory role in antigen presentation. These hypotheses will be tested by studying CD39 expression and heterogeneity in LC, ATP and ADP release by keratinocytes upon exposure to irritant chemicals and by T cells during antigen presentation, the magnitude and kinetics of irritant vs allergic contact hypersensitivity responses in CD3 9-deficient mice, and biological impacts of CD39 agonists vs antagonists. These aims, which may first appear to be mutually independent, are highly related each other (e.g., G-protein coupled receptor signaling via chemokine receptors and P2Y receptors, and counterregulation of apoptosis by AIM and P2X receptors). Thus, the present study will uncover dynamic and complex regulation of LC function, thus, forming both technical and conceptual bases for the development of novel immuno-regulatory and/or antiinflammatory strategies and for their applications to skin cancer and inflammatory skin disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TARGETING ONCOGENE EXPRESSION TO SKIN IN TRANSGENIC MICE Principal Investigator & Institution: Roop, Dennis; Professor; Cell Biology; Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 01-AUG-1990; Project End 31-DEC-2003
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Summary: Skin cancer is the most common neoplasm in the United States with a lifetime risk nearly equal to that of all other cancers combined. Like other cancers, skin carcinogenesis proceeds via the accumulative acquisition of discrete complimentary genetic events. The purpose of this proposal is to dissect the molecular mechanisms that mediate the roles of oncogenes and tumor suppressors in skin carcinogenesis. Based on previous studies the following is proposed: 1) The epidermis has a strong backup system that compensates for p53 loss, which may include novel p53 family members, such as p73. 2) A murine p53-172H mutant (p53m), which is equivalent to the human p53-175H "hot spot mutation" , may have a gain-of-function that can bypass the compensatory response observed for p53 loss in the epidermis. 3) Activation of the cras(Ha) oncogene not only provides the initiation event for skin carcinogenesis, but also contributes greatly to malignant conversion that may be linked to increased genomic instability. 4) Overexpression of the myc oncogene may play a role in skin carcinogenesis and further inhibition of apoptosis by bcl-2 may augment the oncogenic effect of myc. Previously developed transgenic and knockout mouse models, as well as new models will be used to test these hypotheses. The new transgenic models will utilize an inducible, epidermal-specific transgenic/knockout approach which more closely mimics the sporadic focal accumulation of somatic mutations in human tumors. Well-established chemical carcinogenesis protocols and ultraviolet irradiation, which is a critical etiological factor for human skin cancer, will be used as experimental approaches with these mouse models. The development of transgenic models with defined genetic alterations, which have been implicated in human skin cancer, may have a major impact in the development of novel therapeutic approaches in the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF EGFR IN UV-INDUCED SKIN CARCINOGENESIS Principal Investigator & Institution: Hansen, Laura A.; Biomedical Sciences; Creighton University 2500 California St Omaha, NE 68178 Timing: Fiscal Year 2001; Project Start 23-JAN-2001; Project End 31-DEC-2003 Summary: (Taken from the Candidate's Abstract) Ultraviolet radiation (UV) exposure is believed to be the major environmental risk factor contributing to the development of non-melanoma skin cancer, the most common cancer in Caucasians in the United States. UV has been shown to activate the epidermal growth factor receptor (EGFR) in epithelial cells. Exposure to UV also induces cell proliferation, epidermal hyperplasia, apoptosis, and skin tumors in genetically-initiated v-Ha-ras transgenic TG.AC mice. Activation of EGFR is mitogenic to keratinocytes and contributes to skin tumor growth in v-Ha-ras initiated cells. This proposal is designed to test the hypothesis that UVinduced activation of EGFR contributes to UV- induced skin tumor development, suggesting that blockade of EGFR signaling has potential for prevention of UV-induced skin tumors. Specific aim 1 will determine whether UV activates EGFR in mouse and human skin and keratinocytes and whether it is active in UV-induced mouse skin papillomas from v-Ha-ras transgenic TG.AC mice. Specific aim 2 will determine whether EGFR activation by UV results in increased cell proliferation and suppression of apoptosis in both human and mouse keratinocytes and skin. Specific aim 3 will determine whether LTV-induced EGFR activation contributes to v-Ha-ras initiated skin tumorigenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE ANGIOGENESIS
ROLE
OF
PLGF
IN
NORMAL
AND
NEOPLASTIC
Principal Investigator & Institution: Detmar, Michael J.; Associate Professor; Beth Israel Deaconess Medical Center St 1005 Boston, MA 02215 Timing: Fiscal Year 2002; Project Start 13-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Angiogenesis, the formation of new blood vessels from preexisting vessels, is a stepwise process involving vascular hyperpermeability, degradation of extracellular matrix, endothelial cell migration and proliferation, and formation and maturation of new capillary tubes. Whereas primary angiogenesis is a prominent feature of mammalian embryonic development, the normal adult body exhibits little vascular proliferation, with the exception of the female reproductive system and the cycling hair follicle. However, angiogenesis is a characteristic feature of inflammatory and neoplastic diseases and has been thought to represent a promising target for the development of novel anticancer therapies. While vascular endothelial growth factor (VEGF) has been suggested as the major skin and tumor angiogenesis factor, the biological function of placental growth factor (PlGF), an additional member of the vascular endothelial growth factor (VEGF) family of angiogenesis factors, has remained unknown. We recently found that two PlGF isoforms, PlGF-1 and PlGF-2, are upregulated in the chronic inflammatory skin disorder psoriasis and in squamous cell carcinomas of the skin, lesions that are characterized by richly angiogenic stroma. In vitro, epidermal PlGF expression is induced by transforming growth factor-alpha and by hypoxia, similar to VEGF. However, in contrast to VEGF, PlGF is also strongly expressed in dermal microvascular endothelial cells. PlGF-1 selectively activates the VEGF receptor-1 (VEGFR-1; Flt-1) on endothelial cells but not VEGFR-2 (KDR), in contrast to VEGF. PlGF-2 additionally binds to the neuropilin-1 receptor that is also shared by the neuronal guidance molecule semaphorin-D, acting as an antagonist. Recent findings in PlGF-deficient mice suggest that PlGF expression might be necessary for the biological activity of VEGF. To evaluate the importance of PlGF, alone or in concert with VEGF, in normal and pathological angiogenesis, we will investigate the following three aims: 1. Importance of PlGF in normal skin vascularization and in experimental skin inflammation, making use of PlGF-deficient mice, PlGF-2 transgenic mice, and of crosses with VEGF-transgenic mice. 2. Role of PlGF in the multistep process of skin carcinogenesis, elicited by a chemical carcinogen-promoter combination applied to normal, PlGF transgenic mice and PlGF-deficient mice. 3. Importance of transfected PlGF-1, PlGF-2, and semaphorin-D gene constructs for tumor growth, angiogenesis and metastasis of human squamous cell carcinoma and breast cancer xenotransplants. Understanding the molecular mechanisms that control skin and tumor angiogenesis will be the basis for the development of novel therapeutic approaches to treat inflammatory skin diseases and skin cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE SECONDARY PREVENTION OF MELANOMA Principal Investigator & Institution: Oliveria, Susan A.; Sloan-Kettering Institute for Cancer Res New York, NY 10021 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The candidate, Dr Susan A. Oliveria, completed a Doctorate of Science in Epidemiology at Harvard University and is an Assistant Attending Epidemiologist at Memorial SIoan-Kettering Cancer Center. She is applying for a five-year Career Development Award with a focus on the secondary prevention
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and control of melanoma. Several factors speak to the significant potential for skin cancer screening to play an important role in cancer control (1) the very high and rapidly increasing incidence of skin cancer, (2) the significant and growing mortality from melanoma type skin cancer, and (3) the amenability of this type of cancer to early detection and curative surgery given its location on the skin. To provide crucial information that will advance the secondary prevention of melanoma, we will begin to investigate the barriers and facilitators of physician-based skin cancer screening, the accuracy and compliance of high-risk patients in performing skin self-examination, and the potential role of technologies as aids to early detection. These aims are designed to lay the foundation for the development of strategies for early detection and control of melanoma and to facilitate formal studies of the efficacy of secondary prevention programs. The proposed plan for this application is ambitious. The candidate has the commitment and support from her institution to accomplish the goals of this project and the majority of her time and effort will be devoted to research and career development. With the support of this award, she will build on studies that are currently ongoing, continuing to act as a project leader and innovative thinker. She will further be able to conceptualize, develop, and implement new projects outlined in this proposal. The candidate will have the opportunity to enhance and apply existing epidemiological skills while obtaining and developing new skills in health services research, providing her with the necessary professional growth to become an independent researcher. The candidate has had no prior independent funding, but has previous experience coordinating and managing studies. Co-mentors, Drs. Marianne Berwick and Allan Halpern, are experts in dermatoepidemiology and have been working closely with the candidate for the past several years. Dr. Alvin Mushlin (Well Medical College of Cornell University) will assist the candidate with career development and training in health services research which includes coursework, research conferences, journal clubs and academic meetings. The proposed studies should advance our knowledge of opportunities for the secondary prevention and control of melanoma and will allow the candidate to obtain preliminary data, enhance existing epidemiologic skills, and obtain new skills in health services research that will lay the foundation for a productive independent research career. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TOPS-ESTER SUPPRESSION
MODULATION
OF
UVB-INDUCED
IMMUNE
Principal Investigator & Institution: Hsia, Carleton Jc.; Synzyme Technology, Inc. 1 Technology Dr, E-309 Irvine, CA 92618 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2003 Summary: (provided by applicant): A TOPS-ester, diethyl 2,2,6,6-tetramethyl-1-oxyl-4piperidene succinate (DETOPS), is a topical drug selected for development for its unique ability to compartmentalize within skin cells and express antioxidant activity that limits oxidant mediated pathologies including psoriasis, sunburn, skin aging and skin cancer. The objective of this project is to reduce skin cancer by preventing UV radiationinduced immune suppression. The specific aim of this study is to test the capability of DETOPS to interfere with the suppression of the immune system in mice that normally follows biologically-relevant doses of UV radiation. The immune status of SKH-1 hairless mice will be assessed by measuring whether topical application of DETOPS alters UV radiation induced changes in contact hypersensitivity. UV exposed control and DETOPS treated animals will be sensitized by topical application of dinitrofluorobenzene (DNFB) to their unirradiated abdomens. The animals will be
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challenged six days after sensitization by topical application of DNFB to ears. The magnitude of the ear-swelling response will be measured 15-21 hours later. A reduction in ear-swelling normally results from UV radiation-induced immunosuppression. The capacity of DETOPS to prevent skin cancer will be assessed in SKH-1 hairless mice chronically exposed to a biologically-relevant dose of UV radiation. Groups of mice with and without DETOPS treatment will be exposed to UV radiation five days per week for 11 weeks and then monitored for an additional 13 weeks for the appearance of skin tumors. The endpoints of interest for this study are whether DETOPS retards the time to appearance of skin cancer and reduces the yield of tumors. The immune status and skin cancer experiments will be supported by following DETOPS metabolism via pharmacokinetic and pharmacodynamic studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSDERMAL DELIVERY BY ELECTROPORATION AND LIPOSOMES Principal Investigator & Institution: Hui, Sek-Wen W.; Professor and Chairperson; Roswell Park Cancer Institute Corp Buffalo, NY 14263 Timing: Fiscal Year 2002; Project Start 01-FEB-1998; Project End 31-MAR-2006 Summary: We propose to continue our study of transdermal delivery mechanisms with electric pulses. Our long-range goal is to develop convenient, safe and effective methods that can be applied to introduce drugs and vaccines across the skin barrier, for the purpose of controlled release, and topical treatment of local ailments including skin cancer. The stratum corneum (SC), the top layer of the skin, is the major barrier to transdermal transport, and contributes most of the electrical resistance of the skin. Electroporation of the SC can cause a breakdown of this barrier leading to an enhanced transdermal transport by several orders of magnitude. During the past grant period, we have determined the sequence of structural/functional events following the pulse application, leading to a transient permeabilization of the skin. One of our major discoveries is the transport enhancing effect of anionic lipids when applied with electroporation. We propose: (1) To determine the mechanism by which anionic lipids enhance electropermeabilization of the skin-we will test our hypothesis that exogenous anionic lipids mix with SC lipids and form local foci that are susceptible to electropermeabilization. We will then apply our knowledge of the mechanism to maximize the benefit of lipid enhancers. (2) To test the hypothesis that transdermal transport of charged molecules by electroporation is mainly via electrophoresis through hydrophilic electropores (channels)-we will compare the transport of a series of model peptides of varying charge/mass ratio and hydrophobicity. The study will be extended too examine the transport of four insulin analogs. (3) To apply our new-found knowledge to test for facilitated transdermal transport of photodynamic therapy (PDT) drugs through excised porcine skin, live murine skin, and human skin biopsies -ALA, Photofrin and HPPH will be delivered transdermally using our newly developed protocols, and their photodynamical therapeutic effect on colo26 tumor-bearing mice will be evaluated. Once the physicochemical mechanisms of skin permeabilization are known, novel, efficient, minimally invasive protocols can be designed for transdermal drug and vaccine delivery and tissue fluid monitoring. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRIPLEX-DIRECTED HYPERPROLIFERATION
CONTROL
OF
EPIDERMAL
Principal Investigator & Institution: Walborg, Earl F.; Dermigen, Inc. Box 727, 908 Ne Loop 230 Smithville, TX 78957 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2004 Summary: (provided by applicant): Triplex-directed control of epidermal hyperproliferation Epidermal hyperproliferation is a characteristic feature of skin cancer development, especially during the tumor promotion stage. Many of the signal transduction pathways and effector molecules involved in control of the proliferation of epidermal cells have now been identified. Furthermore, the nucleotide sequences of many of the relevant genes have been determined for both mouse and human, providing genetic targets for the development of novel strategies to control proliferation in the epidermis. The proposed research will investigate the pharmacologic potential of triplex-forming oligonucleotides (TFOs) to inhibit transcription of genes known to be involved in the proliferation of epidermal cells, including but not limited to EGFr, erbB2, src, ODC, IGF-lr, COX-2 and cyclin D1 TFOs, designed specifically to target a single site in genes of interest, will be applied locally to the constitutively hyperproliferative skin of K14 TGFalpha transgenic mice in an effort to inhibit their transcription. Therapeutic efficacy will be determined by quantitation of specific gene products by Real Time PCR and Western blotting. For those TFOs that inhibit transcription of specific genes, therapeutic effects at the phenotypic level will be evaluated by measurement of epidermal thickness, immunohistochemical visualization of proliferating cells, and TUNEL assays to assess apoptosis. The proposed experimentation will focus on "proof of principle" prior to application of this therapeutic approach to other animal model systems and extension to human skin disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ULTRAVIOLET B IRRADIATION OF HUMAN KERATINOCYTES Principal Investigator & Institution: Spandau, Dan F.; Dermatology; Indiana UnivPurdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, IN 462025167 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 30-JUN-2006 Summary: The long-term objective of this proposal is to begin to understand the mechanism of UVB-induced skin cancer. Cancers of the skin are the predominant cancer diagnosed in the United States. In addition to the trauma skin cancer causes for its victims, the treatment of skin cancer is also a tremendous burden financially on our healthcare system. Although it is known that the principle carcinogen responsible for the generation of skin cancer is the UV component of sunlight, very little is known about the exact relationship between UV- exposure and the development of skin cancer. The activation of the insulin-like growth factor-1 receptor (IGF-1R) was shown to be a critical factor in determining how keratinocytes respond to UVB exposure. UVB exposure in the presence of activated IGF-1Rs permits keratinocytes to remain viable and not undergo apoptosis. However, a consequence of continued viability is that the irradiated keratinocytes lose the capacity to replicate. We define these two functions of the IGF- 1R in response to IJVB exposure as the induction of survival and senescence. In contrast, in the absence of IGF-1 binding, the same UVB exposure will result in the induction of apoptosis. A critical feature in this model is that in the absence of IGF-1R activation, keratinocytes that survive UVBitradiation still maintain the potential to proliferate. It is this proliferation, following UVB-induced DNA damage that may produce keratinocytes that have oncogenic potential In this proposal, we will begin to
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characterize the mechanism of how the IGF-1R protects normal human keratinocytes from UVB-induced apoptosis. This characterization will be accomplished through the creation of a model system, which will selectively and specifically inactivate the activity of the IGF-1 R. This model system will be used to identify key components of the IGF-1R mediated, UVB-response in human keratinocytes. Through the identification of these components of the UVB-response in human keratinocytes, therapeutic strategies for the prevention of LTVB-induced carcinogenesis can be developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: UNIQUE TOPICAL TREATMENT FOR UV-INDUCED SKIN CANCER Principal Investigator & Institution: Bhatt, Bakul M.; Biomedical Development Corporation 500 Sandau, Ste 200 San Antonio, TX 78216 Timing: Fiscal Year 2003; Project Start 09-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): The goal of this project is to develop a polymerbased vehicle for the topical delivery of caffeine to inhibit UV-induced skin cancer. Despite increased use of sun screen, skin cancer rates continue to rise. Recently, caffeine has been shown to inhibit carcinogenesis in murine models of UV-induced skin tumor formation. The polymer-based delivery system described in this proposal seeks to improve the efficacy and convenience of topically applied caffeine for this application. To achieve this goal, the following Specific Aims will be pursued: Aim 1. Formulate a Polymer-based Topical Delivery System Containing Caffeine Aim 2. Evaluate the Effect of Caffeine Delivered from the Polymer-based Vehicle on Ultraviolet Light-induced Skin Cancer Using a Mouse Model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: USE OF GIS IN ANALYZING ENVIRONMENTAL CANCER RISKS Principal Investigator & Institution: Harris, Robin B.; Assistant Professor of Public Health; None; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2001; Project Start 27-SEP-2001; Project End 31-AUG-2004 Summary: The overall goals of this proposal are to examine geographical variation in the association between cancer risk and potential environmental exposures, in particular arsenic exposure, and to then determine the homogeneity of the associations as the geographical scale changes. Uses of Geographic Information Systems (GIS) have made it more feasible to link multiple sources of descriptive attribute information for various geographic levels with health outcome data. The use of GIS allows the spatial relationships between the data elements to maintained and analyzed. Arsenic exposure may be a causal agent in the development of bladder, lung, kidney, and skin cancers. Furthermore, arsenic is known to vary across geographical locations. Several geographically delineated data sets exist in the State of Arizona that allow for epidemiological exploration of the relationship between arsenic exposure and cancer occurrence. Geocoded cancer incidence and mortality data are available from the Arizona Cancer Registry for bladder, kidney, and lung cancer. Skin cancer data are available from a completed population-based case control study. Arsenic concentrations are available from a multimedia, multipathway survey conducted in Arizona. The specific aims for this proposed research are 1) to evaluate spatial scales and determine relationships between the scale used by the Atlas of Cancer Mortality and scales potentially more useful within the state and 2) to evaluate the relationships between the various cancers and arsenic exposure for the various geographical scales. This proposal presents a cohesive research team that encompasses faculty and staff from various
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colleges within the University of Arizona and state health agencies and will utilize archival data collected by various state agencies and completed epidemiological studies of skin cancer and environmental exposures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: UV DAMAGE, REPAIR AND MUTAGENESIS Principal Investigator & Institution: Pfeifer, Gerd P.; Professor; City of Hope National Medical Center Duarte, CA 91010 Timing: Fiscal Year 2001; Project Start 01-AUG-1992; Project End 31-JUL-2004 Summary: The incidence of skin cancer, the most common type of human cancer, is increasing in the United States and worldwide. The damage of DNA bases by ultraviolet (UV) radiation causes mutations and UV light is strongly implicated in the development of human basal and squamous cell carcinoma as well as the more lethal melanoma. To understand UV carcinogenesis, a more detailed knowledge of the molecular mechanisms of UV damage formation, DNA repair processes, and mutation induction is necessary. We will apply several sensitive techniques to map UV-induced lesions [primarily cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts (6-4)PPs)] and their repair rates at the DNA sequence level. We will continue to investigate the molecular mechanisms of selective UV damage formation in vivo, and to analyze DNA sequence-specific repair rates in several human genes. As part of these aims, we will attempt to develop new methodology to study repair of (6-4) photoproducts at the DNA sequence level. We will measure the major types of DNA lesions and their sequence distribution in solar light irradiated cells. The specific mechanisms of UV mutagenesis will be determined by using a supF shuttle vector and a lacl transgene to study mutagenesis after irradiation with different UV light sources (UVC, UVB, solar light). These studies will address questions as to how the methylation of CpG sequences changes the mutational spectra, which photoproduct contributes most to mutagenesis, what the contribution of CPD deamination to UV mutagenicity is, and whether the frequency of UV-specific mutations correlates with photoproduct frequencies. The sequence context dependence of lesion bypass will be studied with site-specific CPDs and (6-4) photoproducts in a HeLa cell-free extract system. The interference of UV damage with transcription will be analyzed by determining the effects of (6-4) photoproducts on transcription factor binding and by studying the effects of UV lesions (both CPDs and 6-4PPs) in promoters on transcription. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: UV-INDUCED SCLERODERMA
COLLAGEN
REDUCTION--TREATING
SKIN
Principal Investigator & Institution: Kang, Sewon; Associate Professor; Dermatology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 26-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Scleroderma is a progressive, potentially lifethreatening disease of the connective tissue that can cause hardening of the skin, and damage to lungs, heart, kidney, and gastrointestinal tract, The disease may also affect blood vessels, muscles and joints. Scleroderma typically strikes between ages 25 and 55, and women are four times more likely than men to be stricken. An estimated 300,000 persons in the United States have scleroderma. The exact causes of scleroderma are unknown, however, the hallmark of the disease process is over-production of collagen.
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Currently, there is no safe and effective therapy for the disease. Acute exposure to relatively low and safe doses of ultraviolet (UV) irradiation has been shown to reduce skin collagen. This reduction occurs through two simultaneous mechanisms; 1) induction of matrix metalloproteinases (MMP) that degrade skin collagen, and 2) inhibit of new procollagen synthesis. UV irradiation is composed of electromagnetic energy with wavelengths between 290-400nm, and the ability of UV to reduce skin collagen is wavelength-dependent. Short wavelengths-dependent between 290-320nm (referred to as UVB) and long wavelengths between 360-400mn (referred to as UVA1) are most effective. In light-colored people, acute exposure to UVB can cause sun turn, and chronic exposure over many years can cause skin cancer. However, the risks of sunburn and cancer from UVA1 are at least one thousand fold less than from UVB exposure. Therefore, UVA1 phototherapy holds great potential for treatment of cutaneous scleroderma in light-colored persons. In dark-colored people, the ability of UV A1 to reduce skin collagen is largely attenuated by skin pigment, likely making this form of phototherapy ineffective. However, for dark-colored people the risk of sunburn and skin cancer from UVB exposure is substantially less than for light-colored people. Therefore, UVB phototherapy for cutaneous scleroderma in dark-colored persons holds great promise. The broad, long-term objectives of this application are to optimize, evaluate, and investigate the molecular basis of UV phototherapy for the treatment of cutaneous scleroderma. The hypothesis that UV irradiation reduces cutaneous fibrosis of scleroderma by inducing MMPS and simultaneously inhibiting procollagen synthesis, and that efficacy of treatment is dependent on patients' skin pigmentation in combination with the UV wavelength used for treatment will be tested. This application contains five specific aims. Specific aims 1-3 focus on optimization of phototherapy conditions based on measurements of collagen reduction. Specific aim 1 will determine the UVA1 dose-, time- and skin color-dependence for induction of a) MMPs, b) tissue inhibitors of MMPs (TIMPS ), c) collagen degradation, and d) inhibition of procollagen synthesis in light-pigmented human skin in vivo. Specific aim 2 will determine the broadband (290-320 nm) and narrowband UVB (311-313nm) dose- and time-dependence for reduction of collagen (as described for specific aim 1) in dark-pigmented human skin in vivo. Specific aim 3 will determine the kinetics and magnitude of UVA1-induced tanning, and the impact of this tanning on subsequent UV dose dependence for reduction of collagen (as described for specific aim 1) in lightly-pigmented human skin in vivo. Specific aims 4-5 focus on phototherapy clinical trials for treatment of scleroderma. Specific aim 4 will determine, based on information obtained from Specific Aims 1-3, whether a) an optimized regimen of UVA1 irradiation improves cutaneous scleroderma in light-pigmented patients, and b) an optimized regimen of UVB, improves cutaneous scleroderma in dark-pigmented patients. Specific Aim 5 will determine whether clinical improvement in scleroderma with UV phototherapy correlates with MMP induction, collagen degradation, inhibition of procollagen synthesis, levels of profibrotic (TGF-b, CTGF, IL-4, IL-6) and antifibrotic (TNF-a, IFN-g) cytokines, and infiltrating immune cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VALIDATION OF TRANSILLUMINATION AND THE NEVOSCOPE Principal Investigator & Institution: Mullani, Nizar A.; Translite 719 Santa Maria Sugar Land, TX 77478 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 30-SEP-2004 Summary: (provided by applicant): Skin cancer is the most common of all cancers and melanoma is a deadly skin cancer that accounts for over 75% of all the skin cancer
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deaths in the United States. The incidence of melanoma is rising at approximately 3% per year. Early detection of melanoma results in 95% cure rate. But, early detection of melanoma is difficult because of the subtle changes that differentiate a malignant melanoma from a benign mole. Better methods to detect these subtle changes, and more frequent screening for skin cancer, will significantly improve the early detection of melanoma and possibly reduce the number of deaths caused by this disease. Early detection of melanoma requires better methods for examining subtle changes in the pigmentation of the suspicious moles. Side-transillumination, whereby light is directed into the skin from around the suspicious mole, is a new method that makes the skin translucent so that the subsurface structures can be examined with clarity. This technique is used in a prototype device called the Nevoscope and has the potential for improving the early detection of skin cancers such as melanoma and basal cell carcinoma. The goal of this research project is to validate the use of sidetransillumination for the detection of melanoma by comparing its detection accuracy to the established oil epiluminescence method. The second goal of the research project is to develop a commercial model of the Nevoscope for clinical use by the dermatologists that would be easy to use and affordable. The clinical validation study will digitally image 240 skin lesions suspicious for malignancy using the oil-based imaging and the side-transillumination imaging in the same lesion. Two dermatologists that are blinded to the patient history, and who will make a diagnosis based on a semi quantitative scoring method, will read these images. Diagnostic accuracy for melanoma will be computed for the two methods based on pathology-determined diagnosis of the excised lesion. The long-term goal of this research is to validate the side-transillumination method and develop the Nevoscope device into a commercial product for improved early diagnoses of skin cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VICARIOUS DISSONANCE, ATTITUDE CHANGE & SOCIAL IDENTITY Principal Investigator & Institution: Cooper, Joel; Professor; Psychology; Princeton University 4 New South Building Princeton, NJ 085440036 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): In order to minimize people putting themselves at risk for physical and mental disease, it is important to be able to influence their attitudes and behaviors on health related matters. The proposed work suggests a theoretically based way to influence attitudes and behaviors and culminates in a study designed to influence young people to reduce their risk of contracting skin cancer. The research examines the possibility that people's attitudes can change vicariously from the actions of another person. The proposed research specifically addresses vicarious dissonance. The vicarious dissonance hypothesis holds that a person who observes others behaving in a manner inconsistent with their attitudes has the potential to experience cognitive dissonance vicariously, provided that the actor is a member of the observer's social group. The hypothesis combines dissonance with the theoretical construct of social identity. It is suggested that people who share a common group membership, and who feel strongly identified with their group, tend to take on the characteristics, emotions and motivations of the group's prototypical member. Thus, if a group member acts in such a way that produces dissonance in him or herself, it will also produce dissonance in other group members. Even though the other group members did not act in an attitude discrepant fashion, they will nonetheless experience pressure to change their own attitudes. The research in the proposal is divided into four parts. In Part I,
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experiments are designed to show that people change their attitudes as a function of the counterattitudinal behavior of other members of their own group and that the attitude change is indeed based on the process of cognitive dissonance. In Part II, experiments directly assess the social identity hypothesis and are designed to study the importance of the prototypicality of the participant, the actor and the attitude issue. Part III experimentally manipulates the strength of group identification and also examines the relative contributions of interpersonal and intragroup identification. Part IV seeks to demonstrate the impact of vicarious dissonance on an important health-related attitude and behavior. The work is directed toward convincing people at risk of skin cancer to use sun block more frequently and effectively. 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 “skin 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 skin cancer in the PubMed Central database: •
A model for UV-induction of skin cancer. by Ouhtit A, Ananthaswamy HN. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=79671
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A Role for Sunlight in Skin Cancer: UV-Induced p53 Mutations in Squamous Cell Carcinoma. by Brash DE, Rudolph JA, Simon JA, Lin A, McKenna GJ, Baden HP, Halperin AJ, Ponten J. 1991 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52880
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A role of PDGFR[alpha] in basal cell carcinoma proliferation. by Xie J, Aszterbaum M, Zhang X, Bonifas JM, Zachary C, Epstein E, McCormick F. 2001 Jul 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55407
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Aberrant retention of tyrosinase in the endoplasmic reticulum mediates accelerated degradation of the enzyme and contributes to the dedifferentiated phenotype of amelanotic melanoma cells. by Halaban R, Cheng E, Zhang Y, Moellmann G, Hanlon D, Michalak M, Setaluri V, Hebert DN. 1997 Jun 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21028
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Direct Gene Transfer with DNA-Liposome Complexes in Melanoma: Expression, Biologic Activity, and Lack of Toxicity in Humans. by Nabel GJ, Nabel EG, Yang Z, Fox BA, Plautz GE, Gao X, Huang L, Shu S, Gordon D, Chang AE. 1993 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47971
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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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DNA Repair and Aging in Basal Cell Carcinoma: A Molecular Epidemiology Study. by Wei Q, Matanoski GM, Farmer ER, Hedayati MA, Grossman L. 1993 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45925
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Effect of public education aimed at early diagnosis of malignant melanoma: cohort comparison study. by MacKie RM, Bray CA, Leman JA. 2003 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=148894
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Eradication of Human Hepatic and Pulmonary Melanoma Metastases in SCID Mice by Antibody--Interleukin 2 Fusion Proteins. by Becker JC, Pancook JD, Gillies SD, Mendelsohn J, Reisfeld RA. 1996 Apr 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39694
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Histopathogenesis of Malignant Skin Melanoma Induced in Genetically Susceptible Transgenic Mice. by Mintz B, Silvers WK, Klein-Szanto AJ. 1993 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47452
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HLA-G expression in melanoma: A way for tumor cells to escape from immunosurveillance. by Paul P, Rouas-Freiss N, Khalil-Daher I, Moreau P, Riteau B, Le Gal FA, Avril MF, Dausset J, Guillet JG, Carosella ED. 1998 Apr 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22520
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In vivo accumulation of the same anti-melanoma T cell clone in two different metastatic sites. by Hishii M, Andrews D, Boyle LA, Wong JT, Pandolfi F, van den Elsen PJ, Kurnick JT. 1997 Feb 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19799
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Induction of basal cell carcinomas and trichoepitheliomas in mice overexpressing GLI-1. by Nilsson M, Unden AB, Krause D, Malmqwist U, Raza K, Zaphiropoulos PG, Toftgard R. 2000 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16258
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Malignant Melanoma in Transgenic Mice. by Bradl M, Klein-Szanto A, Porter S, Mintz B. 1991 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50770
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Molecular Cloning of a Human Melanoma-Associated Chondroitin Sulfate Proteoglycan. by Pluschke G, Vanek M, Evans A, Dittmar T, Schmid P, Itin P, Filardo EJ, Reisfeld RA. 1996 Sep 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38494
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Mutation Hotspots Due to Sunlight in the p53 Gene of Nonmelanoma Skin Cancers. by Ziegler A, Leffell DJ, Kunala S, Sharma HW, Gailani M, Simon JA, Halperin AJ, Baden HP, Shapiro PE, Bale AE, Brash DE. 1993 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46477
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Notch signalling is linked to epidermal cell differentiation level in basal cell carcinoma, psoriasis and wound healing. by Thelu J, Rossio P, Favier B. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111189
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Novel Ras antagonist blocks human melanoma growth. by Jansen B, SchlagbauerWadl H, Kahr H, Heere-Ress E, Mayer BX, Eichler HG, Pehamberger H, Gana-Weisz M, Ben-David E, Kloog Y, Wolff K. 1999 Nov 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24183
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Observational study of type of surgical training and outcome of definitive surgery for primary malignant melanoma. by MacKie RM, Bray CA, Hole DJ. 2002 Nov 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136925
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Overexpression of Plasminogen Activator Inhibitor 2 in Human Melanoma Cells Inhibits Spontaneous Metastasis in scid/scid Mice. by Mueller BM, Yu YB, Laug WE. 1995 Jan 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42846
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Selective increase in specific alternative splice variants of tyrosinase in murine melanomas: A projected basis for immunotherapy. by Le Fur N, Kelsall SR, Silvers WK, Mintz B. 1997 May 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24678
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Signature p53 Mutation at DNA Cross-Linking Sites in 8-Methoxypsoralen and Ultraviolet A (PUVA)-Induced Murine Skin Cancers. by Nataraj AJ, Black HS, Ananthaswamy HN. 1996 Jul 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38857
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Skin cancer surveillance in renal transplant recipients: questionnaire survey of current UK practice. by Harden PN, Reece SM, Fryer AA, Smith AG, Ramsay HM. 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55574
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Stratum corneum lipids liposomes for the topical delivery of 5-aminolevulinic acid in photodynamic therapy of skin cancer: preparation and in vitro permeation study. by Pierre MB, Tedesco AC, Marchetti JM, Bentley MV. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55336
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Sunlight and skin cancer. by Ananthaswamy HN. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113773
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Sunlight and skin cancer: Another link revealed. by Kraemer KH. 1997 Jan 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33651
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Transgenic Mouse Model of Malignant Skin Melanoma. by Mintz B, Silvers WK. 1993 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47451
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UV and Skin Cancer: Specific p53 Gene Mutation in Normal Skin as a Biologically Relevant Exposure Measurement. by Nakazawa H, English D, Randell PL, Nakazawa K, Martel N, Armstrong BK, Yamasaki H. 1994 Jan 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42947
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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 skin cancer, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “skin cancer” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for skin cancer (hyperlinks lead to article summaries): •
A “round block” purse-string suture in facial reconstruction after operations for skin cancer surgery. Author(s): Patel KK, Telfer MR, Southee R. Source: The British Journal of Oral & Maxillofacial Surgery. 2003 June; 41(3): 151-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804538&dopt=Abstract
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A 10-year prospective study of patients with skin cancer. Author(s): Czarnecki D, Sutton T, Czarnecki C, Culjak G. Source: Journal of Cutaneous Medicine and Surgery. 2002 September-October; 6(5): 4279. Epub 2002 August 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12196892&dopt=Abstract
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A case report of laser resurfacing as a skin cancer prophylaxis. Author(s): Massey RA, Eliezri YD. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1999 June; 25(6): 513-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10469105&dopt=Abstract
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A clinical study of skin cancer: genetic and environmental interactions. Author(s): Smithurst BA, Silverstone H. Source: Public Health. 1975 November; 90(1): 25-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1197612&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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A comment on "Skin cancer, melanoma and sunlight". Author(s): Green AE. Source: American Journal of Public Health. 1977 January; 67(1): 59-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=299799&dopt=Abstract
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A community intervention plan to prevent skin cancer in male golfers. Author(s): Shuliak-Wills L, Navarro K. Source: Can Oncol Nurs J. 2000 Summer; 10(3): 109-11. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11894278&dopt=Abstract
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A comparison of findings from two checklists for the early detection of skin cancer. Author(s): Mahon SM. Source: Mo Nurse. 1997 March-April; 66(2): 12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9574010&dopt=Abstract
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A complicated case of skin cancer in a renal allograft recipient. Author(s): Gruber SA, Stephanian E, Dunn DL. Source: Transplant Sci. 1994 September; 4(1): 17-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7804692&dopt=Abstract
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A course of action on skin cancer. Author(s): Moore G. Source: Bus Health. 2001 April; 19(4): 40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11357281&dopt=Abstract
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A descriptive survey of skin cancer in a geriatric centre 1988-1989. Author(s): Bradley JP. Source: Aust Fam Physician. 1991 October; 20(10): 1461, 1464, 1467-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1793397&dopt=Abstract
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A gene for an autosomal dominant scleroatrophic syndrome predisposing to skin cancer (Huriez syndrome) maps to chromosome 4q23. Author(s): Lee YA, Stevens HP, Delaporte E, Wahn U, Reis A. Source: American Journal of Human Genetics. 2000 January; 66(1): 326-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10631162&dopt=Abstract
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A geographic technique for margin control in skin cancer. Author(s): Rappaport I, Krugman M, Strout E, Marantz C. Source: Annals of Plastic Surgery. 1979 March; 2(3): 264-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=539756&dopt=Abstract
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A graded work site intervention program to improve sun protection and skin cancer awareness in outdoor workers in Israel. Author(s): Azizi E, Flint P, Sadetzki S, Solomon A, Lerman Y, Harari G, Pavlotsky F, Kushelevsky A, Glesinger R, Shani E, Rosenberg L. Source: Cancer Causes & Control : Ccc. 2000 July; 11(6): 513-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10880033&dopt=Abstract
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A look at skin cancer. Author(s): Ross D. Source: Occup Health (Lond). 1988 January; 40(1): 420-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3353061&dopt=Abstract
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A measure of skin familiarity and its role in the early detection of skin cancer. Author(s): Balanda KP, Stanton WR, Baade PD, Lowe JB, Clavarino A. Source: Cancer Detection and Prevention. 2000; 24(2): 156-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10917136&dopt=Abstract
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A model for nurse-led skin cancer surveillance following renal transplantation. Author(s): Reece SM, Harden PN, Smith AG, Ramsay HM. Source: Nephrology Nursing Journal : Journal of the American Nephrology Nurses' Association. 2002 June; 29(3): 257-9, 267. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12164075&dopt=Abstract
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A national approach to skin cancer prevention: the National SunSmart Schools Program. Author(s): Dobbinson S, Peipers A, Reading D, Sinclair C. Source: The Medical Journal of Australia. 1998 November 16; 169(10): 513-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9861906&dopt=Abstract
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A pilot trial of digital imaging in skin cancer. Author(s): Whited JD, Mills BJ, Hall RP, Drugge RJ, Grichnik JM, Simel DL. Source: Journal of Telemedicine and Telecare. 1998; 4(2): 108-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9744167&dopt=Abstract
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A prospective study of incident nonmelanoma skin cancer in heart transplant recipients. Author(s): Espana A, Martinez-Gonzalez MA, Garcia-Granero M, Sanchez-Carpintero I, Rabago G, Herreros J. Source: The Journal of Investigative Dermatology. 2000 December; 115(6): 1158-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11121158&dopt=Abstract
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A randomized trial of skin cancer prevention in aquatics settings: the Pool Cool program. Author(s): Glanz K, Geller AC, Shigaki D, Maddock JE, Isnec MR. Source: Health Psychology : Official Journal of the Division of Health Psychology, American Psychological Association. 2002 November; 21(6): 579-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433010&dopt=Abstract
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A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Author(s): Brash DE, Rudolph JA, Simon JA, Lin A, McKenna GJ, Baden HP, Halperin AJ, Ponten J. Source: Proceedings of the National Academy of Sciences of the United States of America. 1991 November 15; 88(22): 10124-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1946433&dopt=Abstract
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A skin cancer primer for primary care. Author(s): Buttolph G. Source: Jaapa. 2001 April; 14(4): 13-6, 21-2, 25-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11521363&dopt=Abstract
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A skin cancer training programme: evaluation of a postgraduate training for family doctors. Author(s): Girgis A, Sanson-Fisher RW, Howe C, Raffan B. Source: Medical Education. 1995 September; 29(5): 364-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8699975&dopt=Abstract
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A study of acne treatments as risk factors for skin cancer of the head and neck. Author(s): Hogan DJ, To T, Wilson ER, Miller AB, Robson D, Holfeld K, Lane P. Source: The British Journal of Dermatology. 1991 October; 125(4): 343-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1835402&dopt=Abstract
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A study of delayed diagnosis of facial nonmelanoma skin cancer. Author(s): Quatra F, Colonna MR. Source: Plastic and Reconstructive Surgery. 2002 April 15; 109(5): 1762-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932650&dopt=Abstract
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A survey of skin cancer screening in the primary care setting: a comparison with other cancer screenings. Author(s): Altman JF, Oliveria SA, Christos PJ, Halpern AC. Source: Archives of Family Medicine. 2000 November-December; 9(10): 1022-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11115202&dopt=Abstract
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A variant within the DNA repair gene XRCC3 is associated with the development of melanoma skin cancer. Author(s): Winsey SL, Haldar NA, Marsh HP, Bunce M, Marshall SE, Harris AL, Wojnarowska F, Welsh KI. Source: Cancer Research. 2000 October 15; 60(20): 5612-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11059748&dopt=Abstract
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Aberrant expression of p53 tumour-suppressor protein in non-melanoma skin cancer. Author(s): McGregor JM, Yu CC, Dublin EA, Levison DA, MacDonald DM. Source: The British Journal of Dermatology. 1992 November; 127(5): 463-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1467284&dopt=Abstract
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Abnormal location of p16 protein and overexpression of p53 protein in human radiation-induced skin cancer. Author(s): Zhao P, Wang DW, Li G, Gao Y, Li X. Source: Journal of Environmental Pathology, Toxicology and Oncology : Official Organ of the International Society for Environmental Toxicology and Cancer. 1995; 14(1): 25-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7473071&dopt=Abstract
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Abnormal ultraviolet mutagenic spectrum in plasmid DNA replicated in cultured fibroblasts from a patient with the skin cancer-prone disease, xeroderma pigmentosum. Author(s): Seetharam S, Protic-Sabljic M, Seidman MM, Kraemer KH. Source: The Journal of Clinical Investigation. 1987 December; 80(6): 1613-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3680516&dopt=Abstract
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Accuracy of local data on skin cancer. Author(s): Newton J, Redburn J. Source: Bmj (Clinical Research Ed.). 1995 July 15; 311(6998): 189. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7613442&dopt=Abstract
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Accuracy of local data on skin cancer. Computerised data collection systems have not improved data collection. Author(s): Burton JL. Source: Bmj (Clinical Research Ed.). 1995 May 20; 310(6990): 1328. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7773056&dopt=Abstract
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Accuracy of local data on skin cancer. Inaccurate data may lead to insufficient resources. Author(s): Burnett AC, Bland P. Source: Bmj (Clinical Research Ed.). 1995 May 20; 310(6990): 1327-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7773055&dopt=Abstract
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Accuracy of local data on skin cancer. Skin cancer registry data may greatly underestimate cases. Author(s): Roberts DL. Source: Bmj (Clinical Research Ed.). 1995 May 20; 310(6990): 1327. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7773053&dopt=Abstract
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Actinic damage and skin cancer in albinos in northern Tanzania: findings in 164 patients enrolled in an outreach skin care program. Author(s): Lookingbill DP, Lookingbill GL, Leppard B. Source: Journal of the American Academy of Dermatology. 1995 April; 32(4): 653-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7896957&dopt=Abstract
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Actinic keratoses and skin cancer. Author(s): American Academy of Dermatology. Source: Dermatology Nursing / Dermatology Nurses' Association. 2002 December; 14(6): 397-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592796&dopt=Abstract
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Actinic lentigines versus skin cancer risk in albinos in northern Tanzania. Author(s): Lookingbill DP, Lookingbill GL, Leppard B. Source: Journal of the American Academy of Dermatology. 1995 August; 33(2 Pt 1): 299300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7622659&dopt=Abstract
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Activating patients to practice skin cancer prevention: response to mailed materials from physicians versus HMOs. Author(s): Gerbert B, Wolff M, Tschann JM, McPhee SJ, Caspers NM, Martin MJ, Saulovich A. Source: American Journal of Preventive Medicine. 1997 May-June; 13(3): 214-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9181210&dopt=Abstract
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Adjuvant interferon-alpha improves skin cancer survival. Author(s): Kerr C. Source: The Lancet Oncology. 2002 May; 3(5): 262. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067791&dopt=Abstract
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Advanced and recurrent nonmelanoma skin cancer. Author(s): Luce EA. Source: Clin Plast Surg. 1997 October; 24(4): 731-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9342514&dopt=Abstract
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Advances in skin cancer. A tribute to Professor Frederick Helm on the occasion of his 70th birthday. Author(s): Schwartz RA. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1997 November; 23(11): 1005-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9391556&dopt=Abstract
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Alterations of skin-associated lymphoid tissue in the carcinogenesis of arsenical skin cancer. Author(s): Yu HS, Chen GS, Sheu HM, Kao JS, Chang KL, Yu CL. Source: Proc Natl Sci Counc Repub China B. 1992 January; 16(1): 17-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1385879&dopt=Abstract
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Altered expression of bcl-2 family member proteins in nonmelanoma skin cancer. Author(s): Delehedde M, Cho SH, Sarkiss M, Brisbay S, Davies M, El-Naggar AK, McDonnell TJ. Source: Cancer. 1999 April 1; 85(7): 1514-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10193941&dopt=Abstract
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Altered p53 expression in benign and malignant skin lesions from renal transplant recipients and immunocompetent patients with skin cancer: correlation with human papillomaviruses? Author(s): O'Connor DP, Kay EW, Leader M, Murphy GM, Atkins GJ, Mabruk MJ. Source: Diagnostic Molecular Pathology : the American Journal of Surgical Pathology, Part B. 2001 September; 10(3): 190-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11552722&dopt=Abstract
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American Cancer Society perspective on the American College of Preventive Medicine's policy statements on skin cancer prevention and screening. Author(s): McDonald CJ. Source: Ca: a Cancer Journal for Clinicians. 1998 July-August; 48(4): 229-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9676536&dopt=Abstract
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American College of Preventive Medicine policy statement: screening for skin cancer. Author(s): Ferrini RL, Perlman M, Hill L. Source: American Journal of Preventive Medicine. 1998 January; 14(1): 80-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9476841&dopt=Abstract
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An audit of the completeness of non-melanoma skin cancer registration in Greater Glasgow. Author(s): Lucke TW, Hole DJ, Mackie RM. Source: The British Journal of Dermatology. 1997 November; 137(5): 761-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9415237&dopt=Abstract
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An ecologic study of skin cancer and environmental arsenic exposure. Author(s): Wong O, Whorton MD, Foliart DE, Lowengart R. Source: International Archives of Occupational and Environmental Health. 1992; 64(4): 235-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1468791&dopt=Abstract
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Analysis of a two-stage case-control study with cluster sampling of controls: application to nonmelanoma skin cancer. Author(s): Fears TR, Gail MH. Source: Biometrics. 2000 March; 56(1): 190-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10783795&dopt=Abstract
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Annual incidence and predicted risk of nonmelanoma skin cancer in renal transplant recipients. Author(s): Harden PN, Fryer AA, Reece S, Smith AG, Ramsay HM. Source: Transplantation Proceedings. 2001 February-March; 33(1-2): 1302-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11267301&dopt=Abstract
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Application patterns among participants randomized to daily sunscreen use in a skin cancer prevention trial. Author(s): Neale R, Williams G, Green A. Source: Archives of Dermatology. 2002 October; 138(10): 1319-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374537&dopt=Abstract
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Approaches to the prevention and control of skin cancer. Author(s): Cummings SR, Tripp MK, Herrmann NB. Source: Cancer and Metastasis Reviews. 1997 September-December; 16(3-4): 309-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9433642&dopt=Abstract
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Are heart transplant recipients more likely to develop skin cancer than kidney transplant recipients? Author(s): Gjersvik P, Hansen S, Moller B, Leivestad T, Geiran O, Simonsen S, Pfeffer P, Fauchald P. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 2000; 13 Suppl 1: S380-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11112037&dopt=Abstract
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Are people who get skin cancer different? Author(s): Kraemer KH. Source: The Journal of Investigative Dermatology. 1995 June; 104(6): 887-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7769254&dopt=Abstract
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Are renal transplant recipients on CsA-based immunosuppressive regimens more likely to develop skin cancer than those on azathioprine and prednisolone? Author(s): Jensen P, Hansen S, Moller B, Leivestad T, Pfeffer P, Fauchald P. Source: Transplantation Proceedings. 1999 February-March; 31(1-2): 1120. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10083500&dopt=Abstract
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Arsenic and skin cancer: cocarcinogenicity. Author(s): Spoor HJ. Source: Cutis; Cutaneous Medicine for the Practitioner. 1976 November; 18(5): 631-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1022414&dopt=Abstract
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Arsenic as a cause of skin cancer, with notes on its occurrence in Pretoria. Author(s): Schulz EJ. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1967 September 2; 41(33): 819-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6060318&dopt=Abstract
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Arsenic methylation and skin cancer risk in southwestern Taiwan. Author(s): Chen YC, Guo YL, Su HJ, Hsueh YM, Smith TJ, Ryan LM, Lee MS, Chao SC, Lee JY, Christiani DC. Source: Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. 2003 March; 45(3): 241-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661181&dopt=Abstract
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Arsenic methylation capacity and skin cancer. Author(s): Yu RC, Hsu KH, Chen CJ, Froines JR. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2000 November; 9(11): 1259-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11097236&dopt=Abstract
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Arsenic-related Bowen's disease, palmar keratosis, and skin cancer. Author(s): Col M, Col C, Soran A, Sayli BS, Ozturk S. Source: Environmental Health Perspectives. 1999 August; 107(8): 687-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10417369&dopt=Abstract
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Artificial skin for closure and healing of wounds created by skin cancer excisions. Author(s): Prystowsky JH, Siegel DM, Ascherman JA. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2001 July; 27(7): 648-53; Discussion 653-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11442617&dopt=Abstract
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Assessing incidence rates and secular trends in nonmelanocytic skin cancer: which method is best? Author(s): Gallagher RP, Lee T. Source: Journal of Cutaneous Medicine and Surgery. 1998 July; 3(1): 35-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9677258&dopt=Abstract
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Assessment and surgical treatment of basal cell skin cancer. Author(s): Goldberg DP. Source: Clin Plast Surg. 1997 October; 24(4): 673-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9342510&dopt=Abstract
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Association of surface ultraviolet B radiation levels with melanoma and nonmelanoma skin cancer in United States blacks. Author(s): Pennello G, Devesa S, Gail M. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2000 March; 9(3): 291-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10750668&dopt=Abstract
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Attitudes about skin cancer prevention: a qualitative study. Author(s): Gerbert B, Johnston K, Bleecker T, McPhee S. Source: Journal of Cancer Education : the Official Journal of the American Association for Cancer Education. 1996 Summer; 11(2): 96-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8793650&dopt=Abstract
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Awareness of skin cancer by kidney transplant patients. Author(s): Cowen EW, Billingsley EM. Source: Journal of the American Academy of Dermatology. 1999 May; 40(5 Pt 1): 697701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10321596&dopt=Abstract
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Barriers to effective skin cancer detection. Author(s): Wender RC. Source: Cancer. 1995 January 15; 75(2 Suppl): 691-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7804996&dopt=Abstract
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Basic principles of radiotherapy for surgical oncologists. 1--Effects of radiotherapy on superficial tissues. Implications for treating skin cancer. Author(s): Maughan TS. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 1994 February; 20(1): 74-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8131875&dopt=Abstract
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Basic skin cancer triage for teaching melanoma detection. Author(s): Weinstock MA, Goldstein MG, Dube CE, Rhodes AR, Sober AJ. Source: Journal of the American Academy of Dermatology. 1996 June; 34(6): 1063-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8647972&dopt=Abstract
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Be a proponent of skin cancer awareness. Author(s): Hill MJ. Source: Dermatology Nursing / Dermatology Nurses' Association. 1990 April; 2(2): 66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2141527&dopt=Abstract
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Be on the lookout for skin cancer. Author(s): Lemanna L. Source: The American Journal of Nursing. 1996 August; 96(8): 16F-16D. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8712231&dopt=Abstract
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Beachfront screening for skin cancer in Texas Gulf coast surfers. Author(s): Dozier S, Wagner RF Jr, Black SA, Terracina J. Source: Southern Medical Journal. 1997 January; 90(1): 55-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9003825&dopt=Abstract
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Behavior modification obtained by sun protection education coupled with removal of a skin cancer. Author(s): Robinson JK. Source: Archives of Dermatology. 1990 April; 126(4): 477-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2321993&dopt=Abstract
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Behavioral community intervention to reduce the risk of skin cancer. Author(s): Lombard D, Neubauer TE, Canfield D, Winett RA. Source: J Appl Behav Anal. 1991 Winter; 24(4): 677-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1797771&dopt=Abstract
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Behaviors, beliefs, and intentions in skin cancer prevention. Author(s): Cody R, Lee C. Source: Journal of Behavioral Medicine. 1990 August; 13(4): 373-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2246784&dopt=Abstract
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Beta 2-microglobulin changes in skin cancer. Author(s): MacKie RM, Turbitt ML. Source: Journal of the American Academy of Dermatology. 1982 July; 7(1): 134. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6179970&dopt=Abstract
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Beta 2-microglobulin in skin cancer. Author(s): Dahl MV. Source: Journal of the American Academy of Dermatology. 1981 December; 5(6): 698-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6172454&dopt=Abstract
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Bias in the assessment of skin cancer risk in patients with psoriasis. Author(s): Stern RS. Source: Journal of the American Academy of Dermatology. 1982 November; 7(5): 639-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7142472&dopt=Abstract
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Biological amplification factor for sunlight-induced nonmelanoma skin cancer at high latitudes. Author(s): Moan J, Dahlback A, Henriksen T, Magnus K. Source: Cancer Research. 1989 September 15; 49(18): 5207-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2766289&dopt=Abstract
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Brief report: an empirically derived educational program for detecting and preventing skin cancer. Author(s): Katz RC, Jernigan S. Source: Journal of Behavioral Medicine. 1991 August; 14(4): 421-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1942019&dopt=Abstract
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Bullous pemphigoid and metastatic skin cancer. Author(s): Ikai K, Imamura S, Ogino A, Danno K, Hayakawa M. Source: Dermatologica. 1978; 156(1): 55-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=338388&dopt=Abstract
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By the way, doctor. I know I should use sunscreen when I go outdoors in order to reduce my risk for skin cancer. But I've heard that sunscreen blocks my skin's ability to make vitamin D. Is this true? I don't want to miss out on the vitamin D that I need for bone strength. Author(s): Olbricht S. Source: Harvard Women's Health Watch. 2003 June; 10(10): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835160&dopt=Abstract
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Can Internet-based continuing medical education improve physicians' skin cancer knowledge and skills? Author(s): Harris JM, Salasche SJ, Harris RB. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 2001 January; 16(1): 50-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11251750&dopt=Abstract
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Can screening for melanoma and skin cancer save lives? Author(s): Koh HK, Geller AC, Miller DR, Lew RA. Source: Dermatologic Clinics. 1991 October; 9(4): 795-803. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1934653&dopt=Abstract
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Cancer mortality after nonmelanoma skin cancer. Author(s): Spratt JS Jr. Source: Jama : the Journal of the American Medical Association. 1999 January 27; 281(4): 325. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9929084&dopt=Abstract
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Case #8. Skin cancer. Author(s): Haring JI. Source: Rdh. 1993 August; 13(8): 10, 34. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8008856&dopt=Abstract
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Case-control study in a subtropical Australian population to assess the relation between non-melanoma skin cancer and epidermodysplasia verruciformis human papillomavirus DNA in plucked eyebrow hairs. The Nambour Skin Cancer Prevention Study Group. Author(s): Boxman IL, Russell A, Mulder LH, Bavinck JN, Schegget JT, Green A. Source: International Journal of Cancer. Journal International Du Cancer. 2000 April 1; 86(1): 118-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10728604&dopt=Abstract
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Case-referent study on skin cancer and its relation to occupational exposure to polycyclic aromatic hydrocarbons. I. Study design. Author(s): Kubasiewicz M, Starzynski Z. Source: Pol J Occup Med. 1989; 2(3): 221-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2489425&dopt=Abstract
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Case-referent study on skin cancer and its relation to occupational exposure to polycyclic aromatic hydrocarbons. II. Study results. Author(s): Kubasiewicz M, Starzynski Z, Szymczak W. Source: Pol J Occup Med Environ Health. 1991; 4(2): 141-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1799639&dopt=Abstract
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Catching skin cancer early. New treatments aim to keep keratoses from developing into invasive cancer. Author(s): Hruza G. Source: Health News. 2002 December; 8(12): 3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523266&dopt=Abstract
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Celtic ancestry, HLA phenotype and increased risk of skin cancer. Author(s): Long CC, Darke C, Marks R. Source: The British Journal of Dermatology. 1998 April; 138(4): 627-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9640367&dopt=Abstract
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Changes in skin cancer morbidity between 1971-72 and 1977-78. Author(s): Fears TR, Scotto J. Source: Journal of the National Cancer Institute. 1982 August; 69(2): 365-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6955543&dopt=Abstract
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Changes in skin protection behaviors, attitudes, and sunburn: in a population with the highest incidence of skin cancer in the world. Author(s): Baade PD, Balanda KP, Lowe JB. Source: Cancer Detection and Prevention. 1996; 20(6): 566-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8939342&dopt=Abstract
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Changing knowledge and attitudes about skin cancer risk factors in adolescents. Author(s): Mermelstein RJ, Riesenberg LA. Source: Health Psychology : Official Journal of the Division of Health Psychology, American Psychological Association. 1992; 11(6): 371-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1286656&dopt=Abstract
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Changing patterns in incidence of non-melanoma skin cancer. Author(s): Green A. Source: Epithelial Cell Biol. 1992 January; 1(1): 47-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1307938&dopt=Abstract
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Changing trends in non-melanoma skin cancer in South Wales, 1988-98. Author(s): Holme SA, Malinovszky K, Roberts DL. Source: The British Journal of Dermatology. 2000 December; 143(6): 1224-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11122025&dopt=Abstract
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Chapter 8: Human papillomavirus and skin cancer. Author(s): Pfister H. Source: J Natl Cancer Inst Monogr. 2003; (31): 52-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807946&dopt=Abstract
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Characteristics of office-based visits for skin cancer. Dermatologists have more experience than other physicians in managing malignant and premalignant skin conditions. Author(s): Smith ES, Feldman SR, Fleischer AB Jr, Leshin B, McMichael A. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1998 September; 24(9): 981-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9754086&dopt=Abstract
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Chemoprevention of skin cancer in xeroderma pigmentosum. Author(s): Kraemer KH, DiGiovanna JJ, Peck GL. Source: The Journal of Dermatology. 1992 November; 19(11): 715-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1293159&dopt=Abstract
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Chemoprevention of skin cancer. Author(s): Richmond E, Viner JL. Source: Semin Oncol Nurs. 2003 February; 19(1): 62-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12638382&dopt=Abstract
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Chemoprevention of skin cancer. Author(s): Horn MA, Gordon KB. Source: Cancer Treat Res. 2001; 106: 255-82. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11225006&dopt=Abstract
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Chemoprevention of skin cancer. Author(s): Green A. Source: Iarc Sci Publ. 1996; (136): 111-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8791121&dopt=Abstract
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Chemoprevention of skin cancer: current status and future prospects. Author(s): Gupta S, Mukhtar H. Source: Cancer and Metastasis Reviews. 2002; 21(3-4): 363-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12549772&dopt=Abstract
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Chemosurgery for skin cancer: fixed tissue and fresh tissue techniques. Author(s): Mohs FE. Source: Archives of Dermatology. 1976 February; 112(2): 211-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=60916&dopt=Abstract
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Chemosurgery for the microscopically controlled excision of skin cancer. Author(s): Mohs FE. Source: Journal of Surgical Oncology. 1971; 3(3): 257-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5110334&dopt=Abstract
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Chemosurgery in skin cancer. Author(s): Stanewick B. Source: Aorn Journal. 1975 September; 22(3): 351-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1041474&dopt=Abstract
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Chemosurgery of the microscopically controlled excision of skin cancer. Author(s): Mohs FE. Source: Proc Natl Cancer Conf. 1970; 6: 517-27. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5466864&dopt=Abstract
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Chemosurgery: microscopically controlled surgery for skin cancer--past, present and future. Author(s): Mohs FE. Source: J Dermatol Surg Oncol. 1978 January; 4(1): 41-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=618934&dopt=Abstract
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Chemotherapy of skin cancer. Author(s): Klein E, Case RW, Burgess GH. Source: Ca: a Cancer Journal for Clinicians. 1973 July-August; 23(4): 228-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4200101&dopt=Abstract
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Chromosomal radiosensitivity of lymphocytes from skin cancer-prone patients. Author(s): el-Zein R, Shaw P, Tyring SK, Au WW. Source: Mutation Research. 1995 October; 335(2): 143-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7477045&dopt=Abstract
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Cigarette smoking and skin cancer. Author(s): Merimsky O, Inbar M. Source: Clinics in Dermatology. 1998 September-October; 16(5): 585-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9787970&dopt=Abstract
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Clearance of UVB-induced erythema in patients with non-melanoma skin cancer. Author(s): Holmes SC, Aitchison TC, MacKie RM. Source: Photodermatology, Photoimmunology & Photomedicine. 1997 OctoberDecember; 13(5-6): 189-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9542756&dopt=Abstract
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Climate change and skin cancer. Author(s): van der Leun JC, de Gruijl FR. Source: Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology. 2002 May; 1(5): 324-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653470&dopt=Abstract
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Clinical and histological diagnosis of skin cancer. Author(s): Gibbs PM. Source: Aust Clin Rev. 1982 March; (4): 34-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7168696&dopt=Abstract
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Clinical parameters of tumescent anesthesia in skin cancer reconstructive surgery. A review of 86 patients. Author(s): Acosta AE. Source: Archives of Dermatology. 1997 April; 133(4): 451-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9126008&dopt=Abstract
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Clinical risk factors associated with nonmelanoma skin cancer in renal transplant recipients. Author(s): Ramsay HM, Fryer AA, Reece S, Smith AG, Harden PN. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2000 July; 36(1): 167-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10873887&dopt=Abstract
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Codon 12 Harvey-ras mutations are rare events in non-melanoma human skin cancer. Author(s): Campbell C, Quinn AG, Rees JL. Source: The British Journal of Dermatology. 1993 February; 128(2): 111-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8096149&dopt=Abstract
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Coexpression patterns of EGFR, HER2, HER3 and HER4 in non-melanoma skin cancer. Author(s): Krahn G, Leiter U, Kaskel P, Udart M, Utikal J, Bezold G, Peter RU. Source: European Journal of Cancer (Oxford, England : 1990). 2001 January; 37(2): 251-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11166154&dopt=Abstract
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Colleagues in skin cancer prevention: the family practitioner, pediatrician, internist, gynecologist, physician assistant and the nurse. Author(s): Boiko PE. Source: Clinics in Dermatology. 1998 July-August; 16(4): 467-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9699059&dopt=Abstract
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Combined x-ray and gamma-radium ray therapy for skin cancer. Author(s): Wooldridge WE, Lorenc E. Source: Archives of Dermatology. 1967 January; 95(1): 102-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6016298&dopt=Abstract
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Common non pigmented skin cancer. Author(s): Menz J. Source: Aust Fam Physician. 1992 November; 21(11): 1575-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1444994&dopt=Abstract
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Common outpatient skin cancer surgery is safe, but calls for more research. Author(s): Levenson D. Source: Rep Med Guidel Outcomes Res. 2003 March 7; 14(5): 9-10, 12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12817578&dopt=Abstract
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Comparative aspects of nonmelanoma skin cancer. Author(s): Walder EJ. Source: Clinics in Dermatology. 1995 November-December; 13(6): 569-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8882768&dopt=Abstract
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Compensation strategies in sun protection behaviors by a population with nonmelanoma skin cancer. Author(s): Robinson JK. Source: Preventive Medicine. 1992 November; 21(6): 754-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1438120&dopt=Abstract
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Complete follow-up and evaluation of a skin cancer screening in Connecticut. Author(s): Bolognia JL, Berwick M, Fine JA. Source: Journal of the American Academy of Dermatology. 1990 December; 23(6 Pt 1): 1098-106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2273109&dopt=Abstract
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Conditions that mimic skin cancer. Author(s): Jones DL, Jones HS. Source: J Dermatol Surg. 1976 June; 2(3): 209-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=132465&dopt=Abstract
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Congenital syndromes associated with nonmelanoma skin cancer. Author(s): Gherardini G, Bhatia N, Stal S. Source: Clin Plast Surg. 1997 October; 24(4): 649-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9342508&dopt=Abstract
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Conventional diamond fraise vs manual spot dermabrasion with drywall sanding screen for scars from skin cancer surgery. Author(s): Gillard M, Wang TS, Boyd CM, Dunn RL, Fader DJ, Johnson TM. Source: Archives of Dermatology. 2002 August; 138(8): 1035-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12164741&dopt=Abstract
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Cost of nonmelanoma skin cancer treatment in the United States. Author(s): Chen JG, Fleischer AB Jr, Smith ED, Kancler C, Goldman ND, Williford PM, Feldman SR. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2001 December; 27(12): 1035-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11849266&dopt=Abstract
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Counseling to prevent skin cancer: recommendations and rationale of the U.S. Preventive Services Task Force. Author(s): U.S. Preventive Services Task Force. Source: Mmwr. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports / Centers for Disease Control. 2003 October 17; 52(Rr-15): 13-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14561954&dopt=Abstract
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Cover up and stay out of sun to prevent skin cancer. Author(s): Burry JN. Source: Bmj (Clinical Research Ed.). 2003 May 24; 326(7399): 1148. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764010&dopt=Abstract
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COX-2 expression is induced by UVB exposure in human skin: implications for the development of skin cancer. Author(s): Buckman SY, Gresham A, Hale P, Hruza G, Anast J, Masferrer J, Pentland AP. Source: Carcinogenesis. 1998 May; 19(5): 723-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9635856&dopt=Abstract
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Cryosurgery for skin cancer. Author(s): Zitelli JA. Source: Journal of the American Academy of Dermatology. 1992 February; 26(2 Pt 1): 283-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1552085&dopt=Abstract
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Cryosurgery for skin cancer. Author(s): Kuflik EG. Source: J Med Soc N J. 1981 April; 78(4): 277-80. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6939895&dopt=Abstract
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Cryosurgery of skin cancer. Author(s): Epstein E. Source: Cutis; Cutaneous Medicine for the Practitioner. 1976 February; 17(2): 402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1017244&dopt=Abstract
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Cryosurgery of skin cancer--in proper perspective. Author(s): Zacarian SA. Source: J Dermatol Surg. 1975 October; 1(3): 33-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1223162&dopt=Abstract
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Cryotherapy for skin cancer: results over a 5-year period using liquid nitrogen spray cryosurgery. Author(s): Holt PJ. Source: The British Journal of Dermatology. 1988 August; 119(2): 231-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3166941&dopt=Abstract
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Cryotherapy of nonmelanoma skin cancer. Author(s): August PJ. Source: Clinics in Dermatology. 1995 November-December; 13(6): 589-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8882770&dopt=Abstract
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Cumulative sunlight exposure and the risk of developing skin cancer in Florida. Author(s): Schmieder GJ, Yoshikawa T, Mata SM, Streilein JW, Taylor JR. Source: J Dermatol Surg Oncol. 1992 June; 18(6): 517-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1593006&dopt=Abstract
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Curettage, electrosurgery and skin cancer. Author(s): Sheridan AT, Dawber RP. Source: The Australasian Journal of Dermatology. 2000 February; 41(1): 19-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10715896&dopt=Abstract
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Curettage-cryosurgery for non-melanoma skin cancer of the external ear: excellent 5year results. Author(s): Nordin P. Source: The British Journal of Dermatology. 1999 February; 140(2): 291-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10233225&dopt=Abstract
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Current action for skin cancer risk reduction in English schools: a report on a survey carried out for the Department of Health. Author(s): Horsley L, Charlton A, Wiggett C. Source: Health Education Research. 2000 June; 15(3): 249-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10977373&dopt=Abstract
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Current action for skin cancer risk reduction in English schools: pupils' behaviour in relation to sunburn. Author(s): Horsley L, Charlton A, Waterman C. Source: Health Education Research. 2002 December; 17(6): 715-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507347&dopt=Abstract
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Current surgical management of skin cancer in dermatology. Author(s): Roenigk RK, Roenigk HH Jr. Source: J Dermatol Surg Oncol. 1990 February; 16(2): 136-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2406310&dopt=Abstract
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Cutaneous dental sinus imitating skin cancer. Author(s): Mahler D, Joachims HZ, Sharon A. Source: British Journal of Plastic Surgery. 1971 January; 24(1): 78-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5547963&dopt=Abstract
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Cutaneous side effects from laser treatment of the skin: skin cancer, scars, wounds, pigmentary changes, and purpura--use of pulsed dye laser, copper vapor laser, and argon laser. Author(s): Haedersdal M. Source: Acta Derm Venereol Suppl (Stockh). 1999; 207: 1-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10605602&dopt=Abstract
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Cyclooxygenase inhibitors for skin cancer prevention: are they beneficial enough? Author(s): Pentland AP. Source: Archives of Dermatology. 2002 June; 138(6): 823-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12056966&dopt=Abstract
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Daylight saving and skin cancer. Author(s): Robertson DF. Source: The Medical Journal of Australia. 1972 February 5; 1(6): 284. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5014131&dopt=Abstract
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Death from skin cancer among the elderly: epidemiological patterns. Author(s): Weinstock MA. Source: Archives of Dermatology. 1997 October; 133(10): 1207-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9382558&dopt=Abstract
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Decision support software to help primary care physicians triage skin cancer: a pilot study. Author(s): Gerbert B, Bronstone A, Maurer T, Hofmann R, Berger T. Source: Archives of Dermatology. 2000 February; 136(2): 187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10677094&dopt=Abstract
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Decreased number and function of antigen-presenting cells in the skin following application of irritant agents: relevance for skin cancer? Author(s): Lisby S, Baadsgaard O, Cooper KD, Vejlsgaard GL. Source: The Journal of Investigative Dermatology. 1989 June; 92(6): 842-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2786039&dopt=Abstract
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Decreased photodamage and low incidence of non-melanoma skin cancer in 136 sunexposed caucasian patients with vitiligo. Author(s): Schallreuter KU, Tobin DJ, Panske A. Source: Dermatology (Basel, Switzerland). 2002; 204(3): 194-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12037447&dopt=Abstract
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Decreased skin cancer after cessation of therapy with transplant-associated immunosuppressants. Author(s): Otley CC, Coldiron BM, Stasko T, Goldman GD. Source: Archives of Dermatology. 2001 April; 137(4): 459-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11295926&dopt=Abstract
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Defective transcription-coupled repair in Cockayne syndrome B mice is associated with skin cancer predisposition. Author(s): van der Horst GT, van Steeg H, Berg RJ, van Gool AJ, de Wit J, Weeda G, Morreau H, Beems RB, van Kreijl CF, de Gruijl FR, Bootsma D, Hoeijmakers JH. Source: Cell. 1997 May 2; 89(3): 425-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9150142&dopt=Abstract
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Deficiency of a novel retinoblastoma binding protein 2-homolog is a consistent feature of sporadic human melanoma skin cancer. Author(s): Vogt T, Kroiss M, McClelland M, Gruss C, Becker B, Bosserhoff AK, Rumpler G, Bogenrieder T, Landthaler M, Stolz W. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 1999 December; 79(12): 1615-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10616211&dopt=Abstract
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Defining the clinical course of metastatic skin cancer in organ transplant recipients: a multicenter collaborative study. Author(s): Martinez JC, Otley CC, Stasko T, Euvrard S, Brown C, Schanbacher CF, Weaver AL; Transplant-Skin Cancer Collaborative. Source: Archives of Dermatology. 2003 March; 139(3): 301-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622621&dopt=Abstract
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Delayed metastases in skin cancer of the head and neck: the case of the "known primary". Author(s): Talmi YP, Horowitz Z, Wolf M, Kronenberg J. Source: Annals of Plastic Surgery. 1999 March; 42(3): 289-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10096620&dopt=Abstract
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Delayed repair of skin cancer defects. Author(s): Escobar V, Zide MF. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1999 March; 57(3): 271-9; Discussion 279-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10077197&dopt=Abstract
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Deletion mapping of chromosome 3p and 13q and preliminary analysis of the FHIT gene in human nonmelanoma skin cancer. Author(s): Sikkink SK, Rehman I, Rees JL. Source: The Journal of Investigative Dermatology. 1997 December; 109(6): 801-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9406824&dopt=Abstract
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Demarcation of nonmelanoma skin cancer margins in thick excisions using multispectral polarized light imaging. Author(s): Yaroslavsky AN, Neel V, Anderson RR. Source: The Journal of Investigative Dermatology. 2003 August; 121(2): 259-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12880416&dopt=Abstract
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Demographic, psychosocial, and objective risk factors related to perceived risk of skin cancer. Author(s): Webb JA, Friedman LC, Bruce SB, Weinberg AD, Cooper P. Source: Journal of Cancer Education : the Official Journal of the American Association for Cancer Education. 1996 Fall; 11(3): 174-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8877578&dopt=Abstract
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Dendritic cell vaccination for the treatment of skin cancer. Author(s): Nestle FO. Source: Recent Results Cancer Res. 2002; 160: 165-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12079211&dopt=Abstract
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Dermatologists warn nation of increased skin cancer risk. Author(s): Scott R. Source: Journal of the National Cancer Institute. 1992 November 18; 84(22): 1696. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1433355&dopt=Abstract
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Dermatologists, university join in skin cancer study. Author(s): Gunby P. Source: Jama : the Journal of the American Medical Association. 1984 April 6; 251(13): 1652. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6366273&dopt=Abstract
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Dermatology academy drafts skin cancer warning. Author(s): Marwick C. Source: Jama : the Journal of the American Medical Association. 1992 December 2; 268(21): 3041. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1433721&dopt=Abstract
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Evaluation of a skin cancer prevention module for nurses: change in knowledge, selfefficacy, and attitudes. Author(s): McCormick LK, Masse LC, Cummings SS, Burke C. Source: Am J Health Promot. 1999 May-June; 13(5): 282-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10538643&dopt=Abstract
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Evaluation of an asynchronous teleconsultation system for diagnosis of skin cancer and other skin diseases. Author(s): Barnard CM, Goldyne ME. Source: Telemedicine Journal and E-Health : the Official Journal of the American Telemedicine Association. 2000 Winter; 6(4): 379-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11242545&dopt=Abstract
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Evaluation of primary prevention initiatives for skin cancer: a review from a UK perspective. Author(s): Melia J, Pendry L, Eiser JR, Harland C, Moss S. Source: The British Journal of Dermatology. 2000 October; 143(4): 701-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11069445&dopt=Abstract
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Evaluation of skin cancer risk resulting from long term occupational exposure to radiation from ultraviolet lasers in the range from 190 to 400 nm. Author(s): Sterenborg HJ, de Gruijl FR, Kelfkens G, van der Leun JC. Source: Photochemistry and Photobiology. 1991 November; 54(5): 775-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1798754&dopt=Abstract
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Evaluation of the American Academy of Dermatology's National Skin Cancer Early Detection and Screening Program. Author(s): Koh HK, Norton LA, Geller AC, Sun T, Rigel DS, Miller DR, Sikes RG, Vigeland K, Bachenberg EU, Menon PA, Billon SF, Goldberg G, Scarborough DA, Ramsdell WM, Muscarella VA, Lew RA. Source: Journal of the American Academy of Dermatology. 1996 June; 34(6): 971-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8647990&dopt=Abstract
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Evidence of an association between non-Hodgkin's lymphoma and skin cancer. Author(s): Adami J, Frisch M, Yuen J, Glimelius B, Melbye M. Source: Bmj (Clinical Research Ed.). 1995 June 10; 310(6993): 1491-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7787593&dopt=Abstract
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Evidence that a low-fat diet reduces the occurrence of non-melanoma skin cancer. Author(s): Black HS, Thornby JI, Wolf JE Jr, Goldberg LH, Herd JA, Rosen T, Bruce S, Tschen JA, Scott LW, Jaax S, et al. Source: International Journal of Cancer. Journal International Du Cancer. 1995 July 17; 62(2): 165-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7622291&dopt=Abstract
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Excision margins for nonmelanotic skin cancer. Author(s): Thomas DJ, King AR, Peat BG. Source: Plastic and Reconstructive Surgery. 2003 July; 112(1): 57-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832877&dopt=Abstract
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Executive summary of the national Partners in Prevention Skin Cancer Conference: American Academy of Dermatology and Centers for Disease Control and Prevention. Author(s): Bergfeld WF, Farris PK, Wyatt SW, Reilley B, Bewerse BA, Koh HK. Source: Journal of the American Academy of Dermatology. 1997 May; 36(5 Pt 1): 798801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9146552&dopt=Abstract
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Experience with a skin cancer detection clinic at a state fair. Author(s): Kanof EP. Source: N C Med J. 1974 March; 35(3): 159-61. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4524211&dopt=Abstract
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Expression of a retinoid-inducible tumor suppressor, Tazarotene-inducible gene-3, is decreased in psoriasis and skin cancer. Author(s): Duvic M, Helekar B, Schulz C, Cho M, DiSepio D, Hager C, DiMao D, Hazarika P, Jackson B, Breuer-McHam J, Young J, Clayman G, Lippman SM, Chandraratna RA, Robinson NA, Deucher A, Eckert RL, Nagpal S. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 August; 6(8): 3249-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10955811&dopt=Abstract
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Expression of CD44 isoforms in human skin cancer. Author(s): Simon JC, Heider KH, Dietrich A, Wuttig C, Schopf E, Adolf GR, Ponta H, Herrlich P. Source: European Journal of Cancer (Oxford, England : 1990). 1996 July; 32A(8): 1394400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8869105&dopt=Abstract
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Expression of c-fos proto-oncogene mRNA in non-melanoma skin cancer. Author(s): Takahashi S, Pearse AD, Marks R. Source: Journal of Dermatological Science. 1994 February; 7(1): 54-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8193084&dopt=Abstract
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Expression of human macrophage metalloelastase (MMP-12) by tumor cells in skin cancer. Author(s): Kerkela E, Ala-Aho R, Jeskanen L, Rechardt O, Grenman R, Shapiro SD, Kahari VM, Saarialho-Kere U. Source: The Journal of Investigative Dermatology. 2000 June; 114(6): 1113-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10844553&dopt=Abstract
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Expression of the anhidrotic ectodermal dysplasia gene is reduced in skin cancer coinciding with reduced E-cadherin. Author(s): Montonen O, Ezer S, Laurikkala J, Karjalainen-Lindsberg ML, Thesleff I, Kere J, Saarialho-Kere U. Source: Experimental Dermatology. 1998 August; 7(4): 168-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9758413&dopt=Abstract
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Expression of the apoptosis inhibitor, survivin, in nonmelanoma skin cancer and gene targeting in a keratinocyte cell line. Author(s): Grossman D, McNiff JM, Li F, Altieri DC. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 1999 September; 79(9): 1121-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10496530&dopt=Abstract
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Expression of the apoptosis-suppressing protein Bcl-2 in non-melanoma skin cancer. Author(s): Verhaegh ME, Sanders CJ, Arends JW, Neumann HA. Source: The British Journal of Dermatology. 1995 May; 132(5): 740-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7772478&dopt=Abstract
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External irradiation of epithelial skin cancer. Author(s): Brady LW. Source: International Journal of Radiation Oncology, Biology, Physics. 1990 August; 19(2): 491-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2394627&dopt=Abstract
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External irradiation of epithelial skin cancer. Author(s): Lovett RD, Perez CA, Shapiro SJ, Garcia DM. Source: International Journal of Radiation Oncology, Biology, Physics. 1990 August; 19(2): 235-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2394605&dopt=Abstract
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Eye color in skin cancer. Author(s): Prieto JG. Source: International Journal of Dermatology. 1977 June; 16(5): 406-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=873674&dopt=Abstract
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Facial reconstruction for radiation-induced skin cancer. Author(s): Panje WR, Dobleman TJ. Source: Archives of Otolaryngology--Head & Neck Surgery. 1990 April; 116(4): 470-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2138463&dopt=Abstract
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Factors affecting the development of skin cancer after scalp irradiation. Author(s): Modan B, Alfandary E, Shapiro D, Lusky A, Chetrit A, Shewach-Millet M, Movshovitz M. Source: Radiation Research. 1993 July; 135(1): 125-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8327656&dopt=Abstract
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Factors associated with nonmelanoma skin cancer following renal transplantation in Queensland, Australia. Author(s): Ramsay HM, Fryer AA, Hawley CM, Smith AG, Nicol DL, Harden PN. Source: Journal of the American Academy of Dermatology. 2003 September; 49(3): 397406. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963901&dopt=Abstract
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Factors that influence the DNA repair capacity of normal and skin cancer-affected individuals. Author(s): D'Errico M, Calcagnile A, Iavarone I, Sera F, Baliva G, Chinni LM, Corona R, Pasquini P, Dogliotti E. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1999 June; 8(6): 553-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10385147&dopt=Abstract
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False-negative findings in skin cancer and melanoma screening. Author(s): Rampen FH, Casparie-van Velsen JI, van Huystee BE, Kiemeney LA, Schouten LJ. Source: Journal of the American Academy of Dermatology. 1995 July; 33(1): 59-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7601947&dopt=Abstract
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Familial occurrence of multiple nonmelanoma skin cancer. Author(s): Czarnecki D, Zalcberg J, Meehan C, O'Brien T, Leahy S, Bankier A, Nash CG. Source: Cancer Genetics and Cytogenetics. 1992 July 1; 61(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1638472&dopt=Abstract
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Fas/APO-1 promoter polymorphism is not associated with non-melanoma skin cancer. Author(s): Nelson HH, Kelsey KT, Bronson MH, Mott LA, Karagas MR. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2001 July; 10(7): 809-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11440968&dopt=Abstract
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Fluorescence in skin cancer showing verruca senilis in appearance. Author(s): Ito K, Abe T. Source: Bull Pharm Res Inst. 1969 May; 80: 6-12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4195305&dopt=Abstract
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Fluorouracil topically for skin cancer. Author(s): Klein E. Source: Jama : the Journal of the American Medical Association. 1969 February 3; 207(5): 959. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5818266&dopt=Abstract
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Follow-up and evaluation of skin cancer screening in British Columbia. Author(s): Engelberg D, Gallagher RP, Rivers JK. Source: Journal of the American Academy of Dermatology. 1999 July; 41(1): 37-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10411408&dopt=Abstract
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Formative research for developing targeted skin cancer prevention programs for children in multiethnic Hawaii. Author(s): Glanz K, Carbone E, Song V. Source: Health Education Research. 1999 April; 14(2): 155-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10387496&dopt=Abstract
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Fragile histidine triad gene and skin cancer. Author(s): Zanesi N, Croce CM. Source: Eur J Dermatol. 2001 September-October; 11(5): 401-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11525944&dopt=Abstract
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Freckles, moles and melanoma. National Skin Cancer Awareness Week 1988. Author(s): Marks R. Source: Aust Fam Physician. 1988 December; 17(12): 1025. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3240164&dopt=Abstract
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Frequency of skin cancer and other ultraviolet radiation provoked skin lesions of eyelid and periocular region in the 1981-1992 period. Author(s): Talan-Hranilovic J, Cajkovac V, Gregurek-Novak T, Padovan S. Source: Acta Med Croatica. 1996; 50(1): 29-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8776113&dopt=Abstract
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Frequency of skin cancer and solar keratoses in a rural southern county as determined by population sampling. Author(s): Zagula-Mally ZW, Rosenberg EW, Kashgarian M. Source: Cancer. 1974 August; 34(2): 345-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4852096&dopt=Abstract
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Frequent downregulation of DMBT1 and galectin-3 in epithelial skin cancer. Author(s): Mollenhauer J, Deichmann M, Helmke B, Muller H, Kollender G, Holmskov U, Ligtenberg T, Krebs I, Wiemann S, Bantel-Schaal U, Madsen J, Bikker F, Klauck SM, Otto HF, Moldenhauer G, Poustka A. Source: International Journal of Cancer. Journal International Du Cancer. 2003 June 10; 105(2): 149-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673672&dopt=Abstract
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Full proceedings from the National Conference to Develop a National Skin Cancer Agenda. American Academy of Dermatology and Centers for Disease Control and Prevention, Washington, D.C., April 8-10, 1995. Author(s): Goldsmith LA, Koh HK, Bewerse BA, Reilley B, Wyatt SW, Bergfeld WF, Geller AC, Walters PF. Source: Journal of the American Academy of Dermatology. 1996 November; 35(5 Pt 1): 748-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8912571&dopt=Abstract
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Further histochemical studies on cellular response of human skin cancer in the course of fractionated X-ray therapy. Author(s): Vorbrodt A, Hliniak A, Niepolomska W. Source: Radiobiol Radiother (Berl). 1971; 12(5): 547-58. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5145339&dopt=Abstract
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General considerations of the choice of dose limits, averaging areas and weighting factors for the skin in the light of revised skin cancer risk figures and experimental data on non-stochastic effects. Author(s): Charles MW. Source: International Journal of Radiation Biology. 1990 April; 57(4): 841-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1969911&dopt=Abstract
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General guidelines for a low-fat diet effective in the management and prevention of nonmelanoma skin cancer. Author(s): Jaax S, Scott LW, Wolf JE Jr, Thornby JI, Black HS. Source: Nutrition and Cancer. 1997; 27(2): 150-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9121942&dopt=Abstract
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General practitioners' workload after skin cancer/melanoma screening clinics in The Netherlands. Author(s): Rampen FH, Berretty PJ, van Huystee BE, Kiemeney LA, Nijs CH. Source: Dermatology (Basel, Switzerland). 1993; 186(4): 258-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8513190&dopt=Abstract
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Genetic polymorphism in p53 codon 72 and skin cancer in southwestern Taiwan. Author(s): Chen YC, Xu L, Guo YL, Su HJ, Hsueh YM, Smith TJ, Ryan LM, Lee MS, Chaor SC, Lee JY, Christiani DC. Source: Journal of Environmental Science and Health. Part A, Toxic/Hazardous Substances & Environmental Engineering. 2003 January; 38(1): 201-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635827&dopt=Abstract
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Genetic predisposition to skin cancer. Author(s): Halpern AC, Altman JF. Source: Current Opinion in Oncology. 1999 March; 11(2): 132-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10188079&dopt=Abstract
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Genetic syndromes associated with skin cancer. Author(s): Shumrick KA, Coldiron B. Source: Otolaryngologic Clinics of North America. 1993 February; 26(1): 117-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8433838&dopt=Abstract
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Genetically determined susceptibility markers in skin cancer and their application to chemoprevention. Author(s): Hahn H. Source: Iarc Sci Publ. 2001; 154: 93-100. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11220672&dopt=Abstract
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Genetics and skin cancer of xeroderma pigmentosum in Japan. Author(s): Takebe H, Nishigori C, Satoh Y. Source: Japanese Journal of Cancer Research : Gann. 1987 November; 78(11): 1135-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3121549&dopt=Abstract
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Genomic approaches to skin cancer diagnosis. Author(s): Bastian BC, LeBoit PE, Pinkel D. Source: Archives of Dermatology. 2001 November; 137(11): 1507-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11708957&dopt=Abstract
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Geographic distribution of skin cancer. Author(s): Urbach F. Source: Journal of Surgical Oncology. 1971; 3(3): 219-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5110331&dopt=Abstract
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Geographic pathology of skin cancer. Author(s): Jackson R. Source: Journal of Cutaneous Medicine and Surgery. 1999 January; 3(3): 120-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10082590&dopt=Abstract
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Georgia's most common skin cancer: basal cell carcinoma. Author(s): Yancey KB, Guill MA. Source: J Med Assoc Ga. 1982 January; 71(1): 19-21. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7077192&dopt=Abstract
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Giant skin cancer of the chest wall. Author(s): Yuen JC, Habibipour S, Johnson D, Read R. Source: Plastic and Reconstructive Surgery. 1997 November; 100(6): 1614-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9385986&dopt=Abstract
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Glutathione S-transferase polymorphisms and skin cancer after renal transplantation. Author(s): Marshall SE, Bordea C, Haldar NA, Mullighan CG, Wojnarowska F, Morris PJ, Welsh KI. Source: Kidney International. 2000 November; 58(5): 2186-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11044240&dopt=Abstract
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Grenz ray-induced nonmelanoma skin cancer. Author(s): Frentz G. Source: Journal of the American Academy of Dermatology. 1989 September; 21(3 Pt 1): 475-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2674211&dopt=Abstract
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Guidelines for school programs to prevent skin cancer. Author(s): Glanz K, Saraiya M, Wechsler H; Centers for Disease Control and Prevention. Source: Mmwr. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports / Centers for Disease Control. 2002 April 26; 51(Rr-4): 1-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11995901&dopt=Abstract
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Hair follicles, stem cells, and skin cancer. Author(s): Miller SJ, Sun TT, Lavker RM. Source: The Journal of Investigative Dermatology. 1993 March; 100(3): 288S-294S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8440907&dopt=Abstract
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Head and neck skin cancer: preplanned pathologically controlled excision and reconstruction. Author(s): Bray DA. Source: The Laryngoscope. 1982 July; 92(7 Pt 1): 783-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7087648&dopt=Abstract
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Health education about sun and skin cancer: language, ideas and perceptions of young children. Author(s): Hughes BR, Wetton N, Collins M, Newton Bishop JA. Source: The British Journal of Dermatology. 1996 April; 134(4): 624-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8733361&dopt=Abstract
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High incidence and clinical course of aggressive skin cancer in heart transplant patients: a single-center study. Author(s): Adamson R, Obispo E, Dychter S, Dembitsky W, Moreno-Cabral R, Jaski B, Gordon J, Hoagland P, Moore K, King J, Andrews J, Rich M, Daily PO. Source: Transplantation Proceedings. 1998 June; 30(4): 1124-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9636456&dopt=Abstract
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High prevalence of skin cancer in World War II servicemen stationed in the Pacific theater. Author(s): Ramani ML, Bennett RG. Source: Journal of the American Academy of Dermatology. 1993 May; 28(5 Pt 1): 733-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8496417&dopt=Abstract
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High rejection score in the first year and risk of skin cancer in heart transplantation. Author(s): Caforio AL, Belloni Fortina A, Gambino A, Piaserico S, Feltrin G, Tona F, Pompei E, Testolin L, Gai F, Angelini A, Casarotto D, Peserico A. Source: Transplantation Proceedings. 2001 February-March; 33(1-2): 1608-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11267439&dopt=Abstract
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Histochemical observations in skin cancer, keratoacanthoma, and some other tumors of the skin. Author(s): Suurmond D. Source: Dermatologica. 1968; 137(3): 156-67. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4177915&dopt=Abstract
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Histopathological study of changes in connective tissue of the dermis in skin cancer. Author(s): Phadke SA, Bhende YM. Source: Indian Journal of Cancer. 1972 March; 9(1): 1-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5044705&dopt=Abstract
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HLA antigen frequencies in renal transplant recipients and non-immunosuppressed patients with non-melanoma skin cancer. Author(s): Glover MT, Bodmer J, Bodmer W, Kennedy LJ, Brown J, Navarrete C, Kwan JT, Leigh IM. Source: European Journal of Cancer (Oxford, England : 1990). 1993; 29A(4): 520-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8435203&dopt=Abstract
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HLA-A11-associated resistance to skin cancer in renal-transplant patients. Author(s): Bavinck JN, Kootte AM, van der Woude FJ, Vandenbroucke JP, Vermeer BJ, Claas FH. Source: The New England Journal of Medicine. 1990 November 8; 323(19): 1350. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2215624&dopt=Abstract
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Holidays, ozone and skin cancer. Skin cancer in bristol--a comparison of theory with observation. Author(s): Beadle PC, Leach JF. Source: Archives of Dermatological Research. 1982; 274(1-2): 47-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7165367&dopt=Abstract
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Home treatment of skin cancer and solar keratoses. Author(s): Green AC, Beardmore GL. Source: The Australasian Journal of Dermatology. 1988; 29(3): 127-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3272119&dopt=Abstract
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How caustics were used to treat skin cancer. Author(s): Jackson R. Source: J Dermatol Surg Oncol. 1979 December; 5(12): 949-50. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=391839&dopt=Abstract
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How complete has skin cancer registration been in the UK? A study from Yorkshire. Author(s): Stefoski Mikeljevic J, Johnston C, Adamson PJ, Wright A, Bishop JA, Batman P, Neal RD, Forman D. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 2003 April; 12(2): 125-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671536&dopt=Abstract
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How important are somatic mutations and immune control in skin cancer? Reflections on xeroderma pigmentosum. Author(s): Bridges B. Source: Carcinogenesis. 1981; 2(5): 471-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7273327&dopt=Abstract
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How much does the public know about moles, skin cancer and malignant melanoma? The results of a postal survey. Author(s): Newman S, Nichols S, Freer C, Izzard L. Source: Community Med. 1988 November; 10(4): 351-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3233916&dopt=Abstract
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Human cell transfection with skin cancer DNAs. Author(s): Sutherland BM, Bennett PV. Source: Photodermatol. 1985 June; 2(3): 186-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4022820&dopt=Abstract
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Human model systems for studies of skin cancer. Author(s): Kraemer KH. Source: Prog Clin Biol Res. 1989; 298: 25-33. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2748685&dopt=Abstract
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Human papilloma virus infection and its relationship to skin cancer in a group of renal allograft recipients. Author(s): Benton EC, McLaren K, Barr BB, Blessing K, Bunney MH, Rudlinger R, Smith IW, Hunter JA. Source: Current Problems in Dermatology. 1989; 18: 168-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2545416&dopt=Abstract
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Human papilloma virus infection and skin cancer in renal allograft recipients. Author(s): Barr BB, Benton EC, McLaren K, Bunney MH, Smith IW, Blessing K, Hunter JA. Source: Lancet. 1989 January 21; 1(8630): 124-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2563048&dopt=Abstract
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Human papillomavirus and skin cancer. Author(s): McGregor JM, Rustin MH. Source: Postgraduate Medical Journal. 1994 October; 70(828): 682-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7831160&dopt=Abstract
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Human papillomavirus and the development of non-melanoma skin cancer. Author(s): Harwood CA, McGregor JM, Proby CM, Breuer J. Source: Journal of Clinical Pathology. 1999 April; 52(4): 249-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10474513&dopt=Abstract
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Human papillomavirus infection and non-melanoma skin cancer in immunosuppressed and immunocompetent individuals. Author(s): Harwood CA, Surentheran T, McGregor JM, Spink PJ, Leigh IM, Breuer J, Proby CM. Source: Journal of Medical Virology. 2000 July; 61(3): 289-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10861635&dopt=Abstract
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Human papillomavirus infection as a risk factor for anal and perianal skin cancer in a prospective study. Author(s): Bjorge T, Engeland A, Luostarinen T, Mork J, Gislefoss RE, Jellum E, Koskela P, Lehtinen M, Pukkala E, Thoresen SO, Dillner J. Source: British Journal of Cancer. 2002 July 1; 87(1): 61-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12085257&dopt=Abstract
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Human papillomaviruses in non-melanoma skin cancer. Author(s): de Villiers EM, Ruhland A, Sekaric P. Source: Seminars in Cancer Biology. 1999 December; 9(6): 413-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10712888&dopt=Abstract
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Impact of skin cancer education on general practitioners' diagnostic skills. Author(s): Bedlow AJ, Cliff S, Melia J, Moss SM, Seyan R, Harland CC. Source: Clinical and Experimental Dermatology. 2000 March; 25(2): 115-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10733633&dopt=Abstract
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Impact of skin cancer education on medical students' diagnostic skills. Author(s): Cliff S, Bedlow AJ, Melia J, Moss S, Harland CC. Source: Clinical and Experimental Dermatology. 2003 March; 28(2): 214-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653717&dopt=Abstract
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Impact of skin cancer prevention on outdoor aquatics staff: the Pool Cool program in Hawaii and Massachusetts. Author(s): Geller AC, Glanz K, Shigaki D, Isnec MR, Sun T, Maddock J. Source: Preventive Medicine. 2001 September; 33(3): 155-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522155&dopt=Abstract
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Impaired interferon production and natural killer cell activation in patients with the skin cancer-prone disorder, xeroderma pigmentosum. Author(s): Gaspari AA, Fleisher TA, Kraemer KH. Source: The Journal of Clinical Investigation. 1993 September; 92(3): 1135-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7690772&dopt=Abstract
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Importance of human papillomaviruses for the development of skin cancer. Author(s): Meyer T, Arndt R, Christophers E, Nindl I, Stockfleth E. Source: Cancer Detection and Prevention. 2001; 25(6): 533-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132874&dopt=Abstract
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Importance of tumor size and repopulation for radiocurability of skin cancer. Author(s): Maciejewski BA, Skates S, Zajusz A, Lange D. Source: Neoplasma. 1993; 40(1): 51-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8350948&dopt=Abstract
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Improving primary care residents' proficiency in the diagnosis of skin cancer. Author(s): Gerbert B, Bronstone A, Wolff M, Maurer T, Berger T, Pantilat S, McPhee SJ. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 1998 February; 13(2): 91-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9502368&dopt=Abstract
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In vitro radiosensitivity of fibroblasts from thyroid and skin cancer patients treated with X-rays for tinea capitis. Author(s): Ron E, Tarone RE, Modan B, Chaki R, Alfandary E, Parry DM, Makar M, Setlow N, Mulvihill JJ, Miller RW, et al. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1994 April-May; 3(3): 229-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8019372&dopt=Abstract
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In vivo fluorescence spectroscopy of nonmelanoma skin cancer. Author(s): Brancaleon L, Durkin AJ, Tu JH, Menaker G, Fallon JD, Kollias N. Source: Photochemistry and Photobiology. 2001 February; 73(2): 178-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11272732&dopt=Abstract
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In vivo ultraviolet irradiation of human skin results in profound perturbation of the immune system. Relevance to ultraviolet-induced skin cancer. Author(s): Baadsgaard O. Source: Archives of Dermatology. 1991 January; 127(1): 99-109. Review. Erratum In: Arch Dermatol 1991 September; 127(9): 1368. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1824747&dopt=Abstract
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Inaccuracies in certification of nonmelanoma skin cancer deaths. Author(s): Weinstock MA, Bogaars HA, Ashley M, Litle V, Bilodeau E, Kimmel S. Source: American Journal of Public Health. 1992 February; 82(2): 278-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1739165&dopt=Abstract
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Incidence and determinants of skin cancer in a high-risk Australian population. Author(s): Green A, Battistutta D. Source: International Journal of Cancer. Journal International Du Cancer. 1990 September 15; 46(3): 356-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2394501&dopt=Abstract
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Incidence and prediction of nonmelanoma skin cancer post-renal transplantation: a prospective study in Queensland, Australia. Author(s): Carroll RP, Ramsay HM, Fryer AA, Hawley CM, Nicol DL, Harden PN. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 March; 41(3): 676-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612993&dopt=Abstract
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Incidence of cutaneous malignant melanoma in Denmark 1978-1982. Anatomic site distribution, histologic types, and comparison with non-melanoma skin cancer. Author(s): Osterlind A, Hou-Jensen K, Moller Jensen O. Source: British Journal of Cancer. 1988 September; 58(3): 385-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3179192&dopt=Abstract
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Incidence of invasive cancers following basal cell skin cancer. Author(s): Levi F, La Vecchia C, Te VC, Randimbison L, Erler G. Source: American Journal of Epidemiology. 1998 April 15; 147(8): 722-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9554413&dopt=Abstract
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Incidence of invasive cancers following squamous cell skin cancer. Author(s): Levi F, Randimbison L, La Vecchia C, Erler G, Te VC. Source: American Journal of Epidemiology. 1997 November 1; 146(9): 734-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9366621&dopt=Abstract
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Incidence of non-melanocytic skin cancer in Geraldton, Western Australia. Author(s): English DR, Kricker A, Heenan PJ, Randell PL, Winter MG, Armstrong BK. Source: International Journal of Cancer. Journal International Du Cancer. 1997 November 27; 73(5): 629-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9398037&dopt=Abstract
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Incidence of non-melanocytic skin cancer treated in Australia. Author(s): Giles GG, Marks R, Foley P. Source: British Medical Journal (Clinical Research Ed.). 1988 January 2; 296(6614): 13-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3122913&dopt=Abstract
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Incidence of non-melanoma skin cancer in Kauai during 1983. Author(s): Stone JL, Elpern DJ, Reizner G, Farmer ER, Scotto J, Pabo R. Source: Hawaii Med J. 1986 August; 45(8): 281-2, 285-6. No Abstract Available. Erratum In: Hawaii Med J 1986 November; 45(11): 378. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3759449&dopt=Abstract
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Incidence of nonmelanoma skin cancer in New Hampshire and Vermont. Author(s): Serrano H, Scotto J, Shornick G, Fears TR, Greenberg ER. Source: Journal of the American Academy of Dermatology. 1991 April; 24(4): 574-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2033134&dopt=Abstract
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Incidence of non-melanoma skin cancer in West Glamorgan, South Wales. Author(s): Roberts DL. Source: The British Journal of Dermatology. 1990 March; 122(3): 399-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2322501&dopt=Abstract
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Incidence of nonmelanoma skin cancer. Author(s): Urbach F. Source: Dermatologic Clinics. 1991 October; 9(4): 751-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1934649&dopt=Abstract
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Incidence of skin cancer after renal transplantation in The Netherlands. Author(s): Hartevelt MM, Bavinck JN, Kootte AM, Vermeer BJ, Vandenbroucke JP. Source: Transplantation. 1990 March; 49(3): 506-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2316011&dopt=Abstract
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Incidence of skin cancer among Nagasaki atomic bomb survivors (preliminary report). Author(s): Sadamori N, Mine M, Hori M, Fujiwara N, Takahara O, Nishimoto K, Ota H, Noda Y, Namba K, Sadamori M, et al. Source: Journal of Radiation Research. 1990 September; 31(3): 280-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2246753&dopt=Abstract
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Incidence of skin cancer among Nagasaki atomic bomb survivors. Author(s): Sadamori N, Mine M, Honda T. Source: Journal of Radiation Research. 1991 December; 32 Suppl 2: 217-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1823358&dopt=Abstract
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Incidence of skin cancer in 5356 patients following organ transplantation. Author(s): Lindelof B, Sigurgeirsson B, Gabel H, Stern RS. Source: The British Journal of Dermatology. 2000 September; 143(3): 513-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10971322&dopt=Abstract
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Incidence of skin cancer in Japan. Author(s): Miki Y. Source: The Australasian Journal of Dermatology. 1967 December; 9(2): 178-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5588856&dopt=Abstract
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Incidence of skin cancer in Japanese psoriatic patients treated with either methoxsalen phototherapy, Goeckerman regimen, or both therapies. A 10-year follow-up study. Author(s): Torinuki W, Tagami H. Source: Journal of the American Academy of Dermatology. 1988 June; 18(6): 1278-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3385042&dopt=Abstract
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Incidence rates of skin cancer in Townsville, Australia. Author(s): Buettner PG, Raasch BA. Source: International Journal of Cancer. Journal International Du Cancer. 1998 November 23; 78(5): 587-93. Erratum In: Int J Cancer 2001 July 15; 93(2): 302-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9808527&dopt=Abstract
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Increase in incidence rates of basal cell and squamous cell skin cancer in New Hampshire, USA. New Hampshire Skin Cancer Study Group. Author(s): Karagas MR, Greenberg ER, Spencer SK, Stukel TA, Mott LA. Source: International Journal of Cancer. Journal International Du Cancer. 1999 May 17; 81(4): 555-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10225444&dopt=Abstract
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Increase in non-melanoma skin cancer--the King's College Hospital experience (197092). Author(s): Hughes JR, Higgins EM, Smith J, Du Vivier AW. Source: Clinical and Experimental Dermatology. 1995 July; 20(4): 304-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8548987&dopt=Abstract
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Increased cancer mortality following a history of nonmelanoma skin cancer. Author(s): Kahn HS, Tatham LM, Patel AV, Thun MJ, Heath CW Jr. Source: Jama : the Journal of the American Medical Association. 1998 September 9; 280(10): 910-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9739976&dopt=Abstract
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Increased effectiveness of targeted skin cancer screening in the Veterans Affairs population of Northern California. Author(s): Swetter SM, Waddell BL, Vazquez MD, Khosravi VS. Source: Preventive Medicine. 2003 February; 36(2): 164-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590991&dopt=Abstract
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Increased incidence of lung and skin cancer in Finnish silicotic patients. Author(s): Partanen T, Pukkala E, Vainio H, Kurppa K, Koskinen H. Source: J Occup Med. 1994 June; 36(6): 616-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8071722&dopt=Abstract
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Increased risk of skin cancer in patients with ectodermal dysplasia--a contraindication to psoralen and UVA (PUVA) therapy? Author(s): McGregor JM, Hawk JL. Source: Clinical and Experimental Dermatology. 1997 January; 22(1): 56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9330059&dopt=Abstract
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Increased risk of skin cancer: another Celtic myth? A review of Celtic ancestry and other risk factors for malignant melanoma and nonmelanoma skin cancer. Author(s): Long CC, Marks R. Source: Journal of the American Academy of Dermatology. 1995 October; 33(4): 658-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7673500&dopt=Abstract
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Induction of apoptotic cell death in non-melanoma skin cancer by interferon-alpha. Author(s): Rodriguez-Villanueva J, McDonnell TJ. Source: International Journal of Cancer. Journal International Du Cancer. 1995 March 29; 61(1): 110-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7705922&dopt=Abstract
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Inflammatory bowel disease, azathioprine and skin cancer: case report and literature review. Author(s): Austin AS, Spiller RC. Source: European Journal of Gastroenterology & Hepatology. 2001 February; 13(2): 1934. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11246621&dopt=Abstract
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Inhibition of UV-induced p53 mutations and skin cancers by sunscreens: implication for skin cancer prevention. Author(s): Ananthaswamy HN, Ullrich SE, Kripke ML. Source: Experimental Dermatology. 2002; 11 Suppl 1: 40-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444959&dopt=Abstract
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Inhibition of UV-induced p53 mutations by sunscreens: implications for skin cancer prevention. Author(s): Ananthaswamy HN, Loughlin SM, Ullrich SE, Kripke ML. Source: The Journal of Investigative Dermatology. Symposium Proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research. 1998 August; 3(1): 52-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9732059&dopt=Abstract
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Inhibitory effects of perillyl alcohol on UVB-induced murine skin cancer and AP-1 transactivation. Author(s): Barthelman M, Chen W, Gensler HL, Huang C, Dong Z, Bowden GT. Source: Cancer Research. 1998 February 15; 58(4): 711-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9485025&dopt=Abstract
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Intensity of solar ultraviolet radiation and its implications for skin cancer. Author(s): McKenzie RL, Elwood JM. Source: N Z Med J. 1990 April 11; 103(887): 152-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2342671&dopt=Abstract
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Interactive computer technology for skin cancer prevention targeting children. Author(s): Hornung RL, Lennon PA, Garrett JM, DeVellis RF, Weinberg PD, Strecher VJ. Source: American Journal of Preventive Medicine. 2000 January; 18(1): 69-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10808985&dopt=Abstract
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Interferon treatment of skin cancer in patients with epidermodysplasia verruciformis. Author(s): Blanchet-Bardon C, Puissant A, Lutzner M, Orth G, Nutini MT, Guesry P. Source: Lancet. 1981 January 31; 1(8214): 274. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6162063&dopt=Abstract
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International dermatosurgery: a program for detection of skin cancer in the province of Trento, Italy. Author(s): Cristofolini M, Zumiani G, Scappini P, Cristofolini A, Piscioli F. Source: J Dermatol Surg Oncol. 1986 March; 12(3): 241-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3950177&dopt=Abstract
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Interobserver agreement in a community skin cancer screening setting. Author(s): Leffell DJ, Chen YT, Berwick M, Bolognia JL. Source: Journal of the American Academy of Dermatology. 1993 June; 28(6): 1003-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8496441&dopt=Abstract
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Introducing a nurse biopsy role in a skin cancer clinic. Author(s): Godsell G. Source: European Journal of Oncology Nursing : the Official Journal of European Oncology Nursing Society. 2003 March; 7(1): 50-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849575&dopt=Abstract
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Irradiation of epithelial skin cancer. Author(s): Breneman JC. Source: International Journal of Radiation Oncology, Biology, Physics. 1991 October; 21(5): 1393. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1938544&dopt=Abstract
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Is history of squamous-cell skin cancer a marker of poor prognosis in patients with cancer? Author(s): Askling J, Sorensen P, Ekbom A, Frisch M, Melbye M, Glimelius B, Hjalgrim H. Source: Annals of Internal Medicine. 1999 November 2; 131(9): 655-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10577327&dopt=Abstract
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Is it skin cancer--or keratoacanthoma? Author(s): Greene SL, Perry HO. Source: Geriatrics. 1984 September; 39(9): 91-4, 98-9, 102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6468938&dopt=Abstract
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Is the ounce of screening and prevention for skin cancer worth the pound of cure? Author(s): Rigel DS. Source: Ca: a Cancer Journal for Clinicians. 1998 July-August; 48(4): 236-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9676538&dopt=Abstract
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Isn't skin cancer preventable? Author(s): Meyskens FL Jr. Source: Journal of the National Cancer Institute. 1992 March 4; 84(5): 286-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1738176&dopt=Abstract
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Isotretinoin does prevent skin cancer. Author(s): Kraemer KH, DiGiovanna JJ, Peck GL. Source: Archives of Dermatology. 1993 January; 129(1): 43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8420486&dopt=Abstract
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Issues in the delivery of dermatologic surgery for skin cancer. Author(s): Cook J. Source: Dermatologic Clinics. 2000 April; 18(2): 251-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10791152&dopt=Abstract
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Keeping kids safe in the sun. Childhood sunburns can lead to the most deadly skin cancer--melanoma--later in life. Here's how to protect your children. Author(s): Gupta NE. Source: Intouch. 2002 May; 4(3): 22-4, 26. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398043&dopt=Abstract
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Knowledge, attitudes, and behaviors toward skin cancer in Maryland youths. Author(s): Alberg AJ, Herbst RM, Genkinger JM, Duszynski KR. Source: The Journal of Adolescent Health : Official Publication of the Society for Adolescent Medicine. 2002 October; 31(4): 372-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359383&dopt=Abstract
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Lack of selective attendance of participants at skin cancer/melanoma screening clinics. Author(s): Rigel DS, Friedman RJ. Source: Journal of the American Academy of Dermatology. 1994 July; 31(1): 131. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8021360&dopt=Abstract
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Lack of selective attendance of participants at skin cancer/melanoma screening clinics. Author(s): Rampen FH, Berretty PJ, Van Huystee BE, Kiemeney LA, Nijs CH. Source: Journal of the American Academy of Dermatology. 1993 September; 29(3): 423-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8349858&dopt=Abstract
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Laser surgery for skin cancer. Author(s): Goldman L. Source: N Y State J Med. 1977 October; 77(12): 1897-900. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=270016&dopt=Abstract
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Lasers in the treatment of skin cancer. Author(s): Geronemus R, Ashinoff R. Source: Clin Podiatr Med Surg. 1992 July; 9(3): 599-615. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1393983&dopt=Abstract
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Lasers in the treatment of skin cancer. Author(s): Geronemus R, Ashinoff R. Source: Dermatologic Clinics. 1991 October; 9(4): 765-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1934650&dopt=Abstract
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Late results following radiotherapy of skin cancer. Author(s): Hansen PB, Jensen MS. Source: Acta Radiol Ther Phys Biol. 1968 August; 7(4): 307-19. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5748430&dopt=Abstract
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Letter: Multiple sequential skin cancers: the risk of skin cancer in patients with previous skin cancer. Author(s): Biro L, Price E. Source: Archives of Dermatology. 1976 October; 112(10): 1470. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=962351&dopt=Abstract
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Life and death signaling in epidermis: following a planned cell death pathway involving a trail that does not lead to skin cancer. Author(s): Nickoloff BJ, Denning M. Source: The Journal of Investigative Dermatology. 2001 July; 117(1): 1-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11442743&dopt=Abstract
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Life and death signaling pathways contributing to skin cancer. Author(s): Nickoloff BJ, Qin JZ, Chaturvedi V, Bacon P, Panella J, Denning MF. Source: The Journal of Investigative Dermatology. Symposium Proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research. 2002 December; 7(1): 27-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12518789&dopt=Abstract
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Lifestyle high-risk behaviors and demographics may predict the level of participation in sun-protection behaviors and skin cancer primary prevention in the United States: results of the 1998 National Health Interview Survey. Author(s): Santmyire BR, Feldman SR, Fleischer AB Jr. Source: Cancer. 2001 September 1; 92(5): 1315-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11571748&dopt=Abstract
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Lifetime risk for development of skin cancer in the U.S. population: current estimate is now 1 in 5. Author(s): Rigel DS, Friedman RJ, Kopf AW. Source: Journal of the American Academy of Dermatology. 1996 December; 35(6): 10123. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8959974&dopt=Abstract
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Light-induced skin cancer and prolonged uv-erythema. Author(s): Jung EG, Furtwangler M, Klostermann G, Bohnert E. Source: Archives of Dermatological Research. 1980; 267(1): 33-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7387174&dopt=Abstract
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Local chemotherapy of skin cancer. Author(s): Lowenfels AB. Source: Panminerva Medica. 1975 July-August; 17(7-8): 251-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1161330&dopt=Abstract
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Local chemotherapy of skin cancer. Author(s): Lowenfels AB. Source: Panminerva Medica. 1974 March; 16(3): 82-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4449646&dopt=Abstract
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Local flap reconstruction of defects after excision of nonmelanoma skin cancer. Author(s): Jackson IT. Source: Clin Plast Surg. 1997 October; 24(4): 747-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9342515&dopt=Abstract
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Local injection of fluorouracil in skin cancer. Author(s): Lee TC, Lowenfels AN, Rohmans M. Source: Jama : the Journal of the American Medical Association. 1969 April 21; 208(3): 536. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5818539&dopt=Abstract
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Long-term follow-up of skin cancer in the PUVA-48 cooperative study. Author(s): Forman AB, Roenigk HH Jr, Caro WA, Magid ML. Source: Archives of Dermatology. 1989 April; 125(4): 515-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2649011&dopt=Abstract
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Longwave ultraviolet radiation and promotion of skin cancer. Author(s): Matsui MS, DeLeo VA. Source: Cancer Cells. 1991 January; 3(1): 8-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2025494&dopt=Abstract
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Low dose isotretinoin in the prophylaxis of skin cancer in renal transplant patients. Author(s): Bellman BA, Eaglstein WH, Miller J. Source: Transplantation. 1996 January 15; 61(1): 173. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8560565&dopt=Abstract
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Low-dose retinoid therapy for chemoprophylaxis of skin cancer in renal transplant recipients. Author(s): Gibson GE, O'Grady A, Kay EW, Murphy GM. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 1998 January; 10(1): 42-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9552756&dopt=Abstract
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Low-megavoltage electron-beam therapy of head and facial skin cancer using a versatile polystyrene collimator system. Author(s): Johnson TS, Garciga CE, Feldman ME, Holcomb MH. Source: Radiology. 1975 June; 115(3): 695-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=805460&dopt=Abstract
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Lymphocyte counts of patients who have had skin cancer. Author(s): Czarnecki D, Meehan CJ, McColl I, Kulinskaya E. Source: Journal of the American Academy of Dermatology. 1996 May; 34(5 Pt 1): 772-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8632072&dopt=Abstract
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Macrophages in skin cancer: quantitative and functional studies. Author(s): Dammacco F, Miglietta A, Lospalluti M, Meneghini C, Bonomo L. Source: Tumori. 1979 June 30; 65(3): 309-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=462581&dopt=Abstract
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Magnetic resonance imaging evaluation helps to delineate a recurrent skin cancer present under the skin flap. Author(s): Zemtsov A, Reed J, Dixon L. Source: J Dermatol Surg Oncol. 1992 June; 18(6): 508-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1593004&dopt=Abstract
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Management of skin cancer: basal cell epithelioma. Chemosurgery. Author(s): Mohs FE. Source: N Y State J Med. 1968 April 1; 68(7): 871-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5238571&dopt=Abstract
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Management of skin cancer: basal cell epithelioma. Curettage and electrodesiccation. Author(s): Popkin GL. Source: N Y State J Med. 1968 April 1; 68(7): 866-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5238569&dopt=Abstract
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Management of skin cancer: basal cell epithelioma. Roentgen therapy. Author(s): Traenkle HL. Source: N Y State J Med. 1968 April 1; 68(7): 863-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5238568&dopt=Abstract
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Management of skin cancer: basal cell epithelioma. Surgical treatment. Author(s): Gumport SL. Source: N Y State J Med. 1968 April 1; 68(7): 869-71. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5238570&dopt=Abstract
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Mapping of UV photoproducts within ras proto-oncogenes in UV-irradiated cells: correlation with mutations in human skin cancer. Author(s): Tormanen VT, Pfeifer GP. Source: Oncogene. 1992 September; 7(9): 1729-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1501884&dopt=Abstract
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Mapping out skin cancer: Mohs micrographic surgery. Author(s): Mora RG. Source: Va Med Q. 1990 Autumn; 117(8): 361-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2260388&dopt=Abstract
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Margins in excision of skin cancer. Author(s): Trimble JW. Source: Plastic and Reconstructive Surgery. 1984 November; 74(5): 729. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6494332&dopt=Abstract
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Marketing skin cancer prevention to farmers. Author(s): Steiner H, Radosevich D. Source: Ana Publ. 1986 April; (Ch-13): 28-33. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3636084&dopt=Abstract
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Mass screening for skin cancer. Author(s): Tennant FS Jr. Source: American Journal of Public Health. 1981 October; 71(10): 1172-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7270768&dopt=Abstract
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Mathematical models of age and ultraviolet effects on the incidence of skin cancer among whites in the United States. Author(s): Fears TR, Scotto J, Schneiderman MA. Source: American Journal of Epidemiology. 1977 May; 105(5): 420-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=860705&dopt=Abstract
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Measurement and perception of skin colour in a skin cancer survey. Author(s): Green A, Martin NG. Source: The British Journal of Dermatology. 1990 July; 123(1): 77-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2390497&dopt=Abstract
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Measurement of skin cancer incidence. Author(s): Kricker A, Armstrong BK, Parkin DM. Source: Health Reports / Statistics Canada, Canadian Centre for Health Information = Rapports Sur La Sante / Statistique Canada, Centre Canadien D'information Sur La Sante. 1993; 5(1): 63-6. English, French. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8334240&dopt=Abstract
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Meeting The Health of the Nation target for skin cancer: problems with tackling prevention and monitoring trends. Author(s): Melia J, Ellman R, Chamberlain J. Source: Journal of Public Health Medicine. 1994 June; 16(2): 225-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7946499&dopt=Abstract
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Melanocortin receptors, red hair, and skin cancer. Author(s): Rees JL, Healy E. Source: The Journal of Investigative Dermatology. Symposium Proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research. 1997 August; 2(1): 94-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9487023&dopt=Abstract
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Melanocortin-1 receptor gene variants determine the risk of nonmelanoma skin cancer independently of fair skin and red hair. Author(s): Bastiaens MT, ter Huurne JA, Kielich C, Gruis NA, Westendorp RG, Vermeer BJ, Bavinck JN; Leiden Skin Cancer Study Team. Source: American Journal of Human Genetics. 2001 April; 68(4): 884-94. Epub 2001 March 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11254446&dopt=Abstract
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Melanoma and nonmelanoma skin cancer: epidemiology and risk factors. Author(s): Fraser MC, Hartge P, Tucker MA. Source: Semin Oncol Nurs. 1991 February; 7(1): 2-12. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2011655&dopt=Abstract
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Melanoma and skin cancer. Author(s): Kubo K. Source: Hawaii Med J. 1993 May; 52(5): 110, 113. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8320084&dopt=Abstract
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Melanoma and skin cancer. Author(s): Gulbrandson CL. Source: Hawaii Med J. 1993 May; 52(5): 110. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8320083&dopt=Abstract
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Melanoma and skin cancer: evaluation of a health education programme for secondary schools. Author(s): Hughes BR, Altman DG, Newton JA. Source: The British Journal of Dermatology. 1993 April; 128(4): 412-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8494755&dopt=Abstract
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Melanoma skin cancer screenings. A how-to approach. Author(s): Dobes WL Jr. Source: Cancer. 1995 January 15; 75(2 Suppl): 705-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7804998&dopt=Abstract
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Melanoma: the most lethal skin cancer. Author(s): Stern C. Source: Rn. 1987 July; 50(7): 53-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3648924&dopt=Abstract
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Merkel cell tumor. A chemosensitive skin cancer. Author(s): Wynne CJ, Kearsley JH. Source: Cancer. 1988 July 1; 62(1): 28-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3383119&dopt=Abstract
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Metastasis from squamous cell skin cancer of the extremities. Author(s): Ames FC, Hickey RC. Source: Southern Medical Journal. 1982 August; 75(8): 920-3, 932. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7112196&dopt=Abstract
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Metastatic skin cancer; a case with signet ring cell histology. Author(s): Inoue Y, Johno M, Kayashima K, Kako H, Ogawa M, Ono T. Source: The British Journal of Dermatology. 1996 October; 135(4): 634-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8915163&dopt=Abstract
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MICA gene polymorphism is not associated with an increased risk for skin cancer. Author(s): Kennedy C, Naipal A, Gruis NA, Struijk L, ter Schegget J, Willemze R, Claas FH, Bouwes Bavinck JN, Doxiadis II. Source: The Journal of Investigative Dermatology. 2002 April; 118(4): 686-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918717&dopt=Abstract
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Microsatellite instability in human non-melanoma and melanoma skin cancer. Author(s): Quinn AG, Healy E, Rehman I, Sikkink S, Rees JL. Source: The Journal of Investigative Dermatology. 1995 March; 104(3): 309-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7860992&dopt=Abstract
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Microscopically controlled excision of skin cancer in Australia: a report. Author(s): Cains LJ, Land WA. Source: The Australasian Journal of Dermatology. 1979 December; 20(3): 135-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=539959&dopt=Abstract
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Microscopically controlled excision of skin cancer. Author(s): Lim JK, Stewart MM, Pennington DG. Source: The Medical Journal of Australia. 1992 April 6; 156(7): 486-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1556977&dopt=Abstract
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Microscopically controlled excision of skin cancer. Author(s): Trimble JW, Schwartz RA. Source: American Family Physician. 1982 May; 25(5): 187-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7072576&dopt=Abstract
Studies 193
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Microscopically controlled surgery: Mohs' chemosurgery for recurrent and aggressive skin cancer. Author(s): Monheit GD. Source: Ala J Med Sci. 1981 April; 18(2): 147-53. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7246954&dopt=Abstract
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Microvascular free tissue reconstruction following Mohs' micrographic surgery for advanced head and neck skin cancer. Author(s): Ahn ST, Hruza GJ, Mustoe TA. Source: Head & Neck. 1991 March-April; 13(2): 145-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2022480&dopt=Abstract
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Mitochondrial DNA damage in non-melanoma skin cancer. Author(s): Durham SE, Krishnan KJ, Betts J, Birch-Machin MA. Source: British Journal of Cancer. 2003 January 13; 88(1): 90-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556965&dopt=Abstract
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Models relating ultraviolet light and non-melanoma skin cancer incidence. Author(s): Green AE, Hedinger RA. Source: Photochemistry and Photobiology. 1978 August; 28(2): 283-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=395547&dopt=Abstract
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Modulation of biologic endpoints by topical difluoromethylornithine (DFMO), in subjects at high-risk for nonmelanoma skin cancer. Author(s): Einspahr JG, Nelson MA, Saboda K, Warneke J, Bowden GT, Alberts DS. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 January; 8(1): 149-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11801552&dopt=Abstract
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Moh's chemosurgery -- a highly effective and reliable method of treatment for skin cancer. Author(s): Hien NT, Prawer SE, Katz HI. Source: Minn Med. 1981 March; 64(3): 135-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7242512&dopt=Abstract
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Mohs' chemosurgery and skin cancer. Author(s): Olshansky K, Robins P. Source: Southern Medical Journal. 1976 September; 69(9): 1126-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=968524&dopt=Abstract
194 Skin Cancer
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Mohs' chemosurgery for skin cancer, microscopically controlled excision. Author(s): McCall MW, Greenway HT, Mohs FE. Source: J Ky Med Assoc. 1981 September; 79(9): 613-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7021724&dopt=Abstract
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Mohs micrographic surgery for facial skin cancer. Author(s): Jones NS. Source: Archives of Facial Plastic Surgery : Official Publication for the American Academy of Facial Plastic and Reconstructive Surgery, Inc. and the International Federation of Facial Plastic Surgery Societies. 2002 April-June; 4(2): 125. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020214&dopt=Abstract
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Mohs micrographic surgery for facial skin cancer. Author(s): Vuyk HD, Lohuis PJ. Source: Clinical Otolaryngology and Allied Sciences. 2001 August; 26(4): 265-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11559334&dopt=Abstract
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Mohs micrographic surgery for nonmelanoma skin cancer. Author(s): Telfer NR. Source: Clinics in Dermatology. 1995 November-December; 13(6): 593-600. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8882771&dopt=Abstract
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Mohs micrographic surgery for nonmelanoma skin cancer. Author(s): Frankel DH. Source: Hosp Pract (Off Ed). 1990 February 28; 25(2A): 15-6, 19-22. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2105979&dopt=Abstract
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Mohs micrographic surgery for periorbital skin cancer. Author(s): Monheit GD, Callahan MA, Callahan A. Source: Dermatologic Clinics. 1989 October; 7(4): 677-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2791356&dopt=Abstract
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Mohs Micrographic Surgery for skin cancer. Author(s): Leslie DF, Greenway HT. Source: The Australasian Journal of Dermatology. 1991; 32(3): 159-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1823112&dopt=Abstract
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Mohs micrographic surgery for skin cancer. Author(s): Dinehart SM, Pollack SV. Source: Cancer Treatment Reviews. 1989 December; 16(4): 257-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2700318&dopt=Abstract
Studies 195
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Mohs' surgery as an approach to treatment of multiple skin cancer in rhinophyma. Author(s): Tamir G, Murakami C, Berg D. Source: Journal of Cutaneous Medicine and Surgery. 1999 January; 3(3): 169-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10082599&dopt=Abstract
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Mohs' surgery for skin cancer. Author(s): Robinson JK. Source: The American Journal of Nursing. 1982 February; 82(2): 282-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6915713&dopt=Abstract
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Mohs surgery in the treatment of skin cancer. Author(s): Abide JM. Source: J Miss State Med Assoc. 1986 December; 27(12): 313-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3806667&dopt=Abstract
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Molecular epidemiology of skin cancers: DNA repair and non-melanocytic skin cancer. Author(s): Hall J, Artuso M, English DR. Source: Ann Ist Super Sanita. 1996; 32(1): 43-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8967724&dopt=Abstract
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Molecular genetic approaches to non-melanoma and melanoma skin cancer. Author(s): Rees JL, Healy E. Source: Clinical and Experimental Dermatology. 1996 July; 21(4): 253-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8959894&dopt=Abstract
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Molecular genetics of human non-melanoma skin cancer. Author(s): Quinn AG. Source: Cancer Surv. 1996; 26: 89-114. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8783569&dopt=Abstract
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Molecular genetics of skin cancer. Author(s): Walsh DS. Source: Adv Dermatol. 1997; 13: 167-204. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9551144&dopt=Abstract
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More on skin cancer after the extravasation of doxorubicin. Author(s): Silverman HI. Source: The New England Journal of Medicine. 1995 July 27; 333(4): 257. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7791848&dopt=Abstract
196 Skin Cancer
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Mortality from nonmelanotic skin cancer. Author(s): Gormley DE. Source: International Journal of Dermatology. 1988 January-February; 27(1): 67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3346130&dopt=Abstract
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Mortality from nonmelanotic skin cancer. Author(s): Garmley DE. Source: International Journal of Dermatology. 1989 May; 28(4): 279. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2722348&dopt=Abstract
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Motivating the public to take advantage of skin cancer screening. Author(s): Girasek DC. Source: Journal of the American Academy of Dermatology. 1986 August; 15(2 Pt 1): 30915. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3745540&dopt=Abstract
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Multidisciplinary surgical approach to the treatment of perinasal nonmelanoma skin cancer. Author(s): Siegle RJ, Schuller DE. Source: Dermatologic Clinics. 1989 October; 7(4): 711-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2676285&dopt=Abstract
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Multidisciplinary treatment of facial skin cancer. Author(s): Calhoun KH, Wagner RF. Source: Tex Med. 1991 December; 87(12): 64-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1801295&dopt=Abstract
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Multimedia public/professional skin cancer education in a multiethnic setting. Author(s): Putnam GL, Brannon B, Yanagisako KL. Source: Prog Clin Biol Res. 1982; 83: 437-48. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7089004&dopt=Abstract
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Multiple nonmelanoma skin cancer associated with HLA DR7 in southern Australia. Author(s): Czarnecki DB, Lewis A, Nicholson I, Tait B. Source: Cancer. 1991 July 15; 68(2): 439-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2070340&dopt=Abstract
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Multiple nonmelanoma skin cancer in an exposed Australian population. Author(s): Raasch BA, Buettner PG. Source: International Journal of Dermatology. 2002 October; 41(10): 652-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390187&dopt=Abstract
Studies 197
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Multiple non-melanoma skin cancer: evidence that different MHC genes are associated with different cancers. Author(s): Czarnecki D, Tait B, Nicholson I, Lewis A. Source: Dermatology (Basel, Switzerland). 1994; 188(2): 88-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8136554&dopt=Abstract
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Multiple risk factors associated with arsenic-induced skin cancer: effects of chronic liver disease and malnutritional status. Author(s): Hsueh YM, Cheng GS, Wu MM, Yu HS, Kuo TL, Chen CJ. Source: British Journal of Cancer. 1995 January; 71(1): 109-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7819025&dopt=Abstract
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Multiple sequential skin cancers. The risk of skin cancer in patients with previous skin cancer. Author(s): Bergstresser PR, Halprin KM. Source: Archives of Dermatology. 1975 August; 111(8): 995-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1232942&dopt=Abstract
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Mutations of Fas (APO-1/CD95) and p53 genes in nonmelanoma skin cancer. Author(s): Boldrini L, Loggini B, Gisfredi S, Zucconi Y, Baldinotti F, Fogli A, Simi P, Cervadoro G, Barachini P, Basolo F, Pingitore R, Fontanini G. Source: Journal of Cutaneous Medicine and Surgery. 2003 March-April; 7(2): 112-8. Epub 2002 November 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447615&dopt=Abstract
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Mycosis fungoides, nitrogen mustard and skin cancer. Author(s): Du Vivier A, Vonderheid EC, Van Scott EJ, Urbach F. Source: The British Journal of Dermatology. 1978 July; 99(1): 61-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=678466&dopt=Abstract
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Name the spot. National Skin Cancer Awareness Week 23 to 29 November. Author(s): Marks R. Source: Aust Fam Physician. 1992 October; 21(10): 1381-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1444965&dopt=Abstract
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Nasal valve dysfunction after Mohs surgery for skin cancer of the nose. Author(s): Reynolds MB, Gourdin FW. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1998 September; 24(9): 1011-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9754090&dopt=Abstract
198 Skin Cancer
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Natural cell-mediated cytotoxicity and skin cancer in long-term renal allograft recipients. Author(s): Rigby RJ, Gollogly RK, Robinson MF, Hardie IR, Petrie JJ. Source: Transplantation. 1984 May; 37(5): 526-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6375007&dopt=Abstract
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Needs assessment in continuing medical education. Its feasibility and value in a seminar about skin cancer for general practitioners. Author(s): Ward J, Macfarlane S. Source: The Medical Journal of Australia. 1993 July 5; 159(1): 20-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8316106&dopt=Abstract
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New light on skin cancer mechanisms. Author(s): Marwick C. Source: Jama : the Journal of the American Medical Association. 1995 August 9; 274(6): 445-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7629937&dopt=Abstract
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New primary cancers after squamous cell skin cancer. Author(s): Frisch M, Melbye M. Source: American Journal of Epidemiology. 1995 May 15; 141(10): 916-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7741121&dopt=Abstract
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New primary nonmelanoma skin cancer in patients with a history of squamous cell carcinoma of the skin. Implications and recommendations for follow-up. Author(s): Frankel DH, Hanusa BH, Zitelli JA. Source: Journal of the American Academy of Dermatology. 1992 May; 26(5 Pt 1): 720-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1583171&dopt=Abstract
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NJ skin cancer screening program. Author(s): Papa CM. Source: N J Med. 1989 May; 86(5): 353-5, 358. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2739946&dopt=Abstract
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No difference in skin cancer incidence with or without cyclosporine--a 5-year perspective. Author(s): Blohme I, Larko O. Source: Transplantation Proceedings. 1992 February; 24(1): 313. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1539292&dopt=Abstract
Studies 199
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Non melanoma skin cancer and solar keratoses in Australia. Author(s): Marks R. Source: J Med Assoc Thai. 1987 April; 70 Suppl 3: 17-20. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3625074&dopt=Abstract
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Non melanoma skin cancer of the scalp. On the etiology. Author(s): Frentz G, Sorensen JL, Flod K. Source: Acta Dermato-Venereologica. 1989; 69(2): 142-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2564232&dopt=Abstract
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Non-Hodgkin's lymphoma and skin cancer. American data refute ultraviolet hypothesis. Author(s): Newton R. Source: Bmj (Clinical Research Ed.). 1995 September 16; 311(7007): 750-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7549709&dopt=Abstract
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Non-Hodgkin's lymphoma and skin cancer. Association may be iatrogenic. Author(s): Vickers M. Source: Bmj (Clinical Research Ed.). 1995 September 16; 311(7007): 750; Author Reply 750-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7549708&dopt=Abstract
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Non-Hodgkin's lymphoma and skin cancer. Pathogenesis is multifactorial. Author(s): Gniadecki R. Source: Bmj (Clinical Research Ed.). 1995 September 16; 311(7007): 749-50; Author Reply 750-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7549707&dopt=Abstract
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Non-Hodgkin's lymphoma and skin cancer. Ultraviolet light is unlikely explanation for association. Author(s): Sasieni P, Bataille V. Source: Bmj (Clinical Research Ed.). 1995 September 16; 311(7007): 749; Author Reply 750-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7549706&dopt=Abstract
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Non-melanoma skin cancer and keratoacanthoma in Filipinos: an incidence report from Kauai, Hawaii. Author(s): Chuang TY, Reizner GT, Elpern DJ, Stone JL, Farmer ER. Source: International Journal of Dermatology. 1993 October; 32(10): 717-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8225710&dopt=Abstract
200 Skin Cancer
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Non-melanoma skin cancer and solar keratoses II analytical results of the South Wales Skin Cancer Study. Author(s): Harvey I, Frankel S, Marks R, Shalom D, Nolan-Farrell M. Source: British Journal of Cancer. 1996 October; 74(8): 1308-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8883423&dopt=Abstract
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Non-melanoma skin cancer and solar keratoses in Australia--a review. Author(s): Marks R. Source: European Journal of Epidemiology. 1985 December; 1(4): 319-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3842121&dopt=Abstract
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Non-melanoma skin cancer and solar keratoses. I. Methods and descriptive results of the South Wales Skin Cancer Study. Author(s): Harvey I, Frankel S, Marks R, Shalom D, Nolan-Farrell M. Source: British Journal of Cancer. 1996 October; 74(8): 1302-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8883422&dopt=Abstract
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Non-melanoma skin cancer and the 'new National Health Service': implications for U.K. dermatology? Author(s): Eedy DJ. Source: The British Journal of Dermatology. 2000 March; 142(3): 397-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10735941&dopt=Abstract
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Nonmelanoma skin cancer associated with use of a tanning bed. Author(s): Lever LR, Lawrence CM. Source: The New England Journal of Medicine. 1995 May 25; 332(21): 1450-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7723815&dopt=Abstract
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Non-melanoma skin cancer for dentists. Author(s): Herrin HK. Source: Tex Dent J. 1996 June; 113(6): 31-3. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9518844&dopt=Abstract
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Nonmelanoma skin cancer in an Irish population: an appraisal of risk factors. Author(s): Healy E, Collins P, Barnes L. Source: Ir Med J. 1995 March-April; 88(2): 58-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7775148&dopt=Abstract
Studies 201
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Non-melanoma skin cancer in Hong Kong. Author(s): Burd A, Cheung MK. Source: Hong Kong Medical Journal = Xianggang Yi Xue Za Zhi / Hong Kong Academy of Medicine. 2001 September; 7(3): 322-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11590280&dopt=Abstract
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Nonmelanoma skin cancer in Japanese ethnic Hawaiians in Kauai, Hawaii: an incidence report. Author(s): Chuang TY, Reizner GT, Elpern DJ, Stone JL, Farmer ER. Source: Journal of the American Academy of Dermatology. 1995 September; 33(3): 422-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7657865&dopt=Abstract
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Nonmelanoma skin cancer in Japanese residents of Kauai, Hawaii. Author(s): Leong GK, Stone JL, Farmer ER, Scotto J, Reizner GT, Burnett TS, Elpern DJ. Source: Journal of the American Academy of Dermatology. 1987 August; 17(2 Pt 1): 2338. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3624562&dopt=Abstract
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Nonmelanoma skin cancer in northern Finland. Author(s): Koskinen A, Oikarinen A. Source: International Journal of Dermatology. 1996 October; 35(10): 700-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8891816&dopt=Abstract
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Nonmelanoma skin cancer in organ transplant patients. Author(s): Jemec GB, Holm EA. Source: Transplantation. 2003 February 15; 75(3): 253-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589142&dopt=Abstract
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Non-melanoma skin cancer in renal transplant recipients: the extent of the problem and a strategy for management. Author(s): Glover MT, Niranjan N, Kwan JT, Leigh IM. Source: British Journal of Plastic Surgery. 1994 March; 47(2): 86-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8149064&dopt=Abstract
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Nonmelanoma skin cancer in the United States: incidence. Author(s): Miller DL, Weinstock MA. Source: Journal of the American Academy of Dermatology. 1994 May; 30(5 Pt 1): 774-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8176018&dopt=Abstract
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Non-melanoma skin cancer may be a marker of poor prognosis in patients with nonHodgkin's lymphoma. Author(s): Hjalgrim H, Frisch M, Storm HH, Glimelius B, Pedersen JB, Melbye M. Source: International Journal of Cancer. Journal International Du Cancer. 2000 March 1; 85(5): 639-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10699942&dopt=Abstract
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Nonmelanoma skin cancer mortality in the United States, 1969 through 1988. Author(s): Weinstock MA. Source: Archives of Dermatology. 1993 October; 129(10): 1286-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8215493&dopt=Abstract
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Nonmelanoma skin cancer mortality. A population-based study. Author(s): Weinstock MA, Bogaars HA, Ashley M, Litle V, Bilodeau E, Kimmel S. Source: Archives of Dermatology. 1991 August; 127(8): 1194-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1863078&dopt=Abstract
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Non-melanoma skin cancer occurring in patients treated with PUVA five to ten years after first treatment. Author(s): Stern RS, Lange R. Source: The Journal of Investigative Dermatology. 1988 August; 91(2): 120-4. Erratum In: J Invest Dermatol 1989 February; 92(2): 300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3397587&dopt=Abstract
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Non-melanoma skin cancer. Author(s): Czarnecki D. Source: The Medical Journal of Australia. 1996 August 19; 165(4): 235, 238. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8773661&dopt=Abstract
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Non-melanoma skin cancer. Author(s): Kearsley JH. Source: The Medical Journal of Australia. 1996 August 19; 165(4): 235, 238. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8773660&dopt=Abstract
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Non-melanoma skin cancer. Author(s): Yeatman J, Marks R. Source: The Medical Journal of Australia. 1996 April 15; 164(8): 492-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8614345&dopt=Abstract
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Non-melanoma skin cancer. Author(s): Harvey I, Shalom D, Marks RM, Frankel SJ. Source: Bmj (Clinical Research Ed.). 1989 November 4; 299(6708): 1118-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2513017&dopt=Abstract
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Non-melanoma skin cancer. Author(s): du Vivier A. Source: Practitioner. 1984 June; 228(1392): 549-53. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6739422&dopt=Abstract
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Non-melanoma skin cancer: a case-control study on risk factors and protective measures. Author(s): Suarez-Varela MM, Llopis Gonzalez A, Ferrer Caraco E. Source: Journal of Environmental Pathology, Toxicology and Oncology : Official Organ of the International Society for Environmental Toxicology and Cancer. 1996; 15(2-4): 25561. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9216817&dopt=Abstract
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Nonmelanoma skin cancer: an episode of care management approach. Author(s): Housman TS, Williford PM, Feldman SR, Teuschler HV, Fleischer AB Jr, Goldman ND, Balkrishnan R, Chen GJ. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 July; 29(7): 700-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828693&dopt=Abstract
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Non-melanoma skin cancer: ten years of cancer-registry-based surveillance. Author(s): Kaldor J, Shugg D, Young B, Dwyer T, Wang YG. Source: International Journal of Cancer. Journal International Du Cancer. 1993 April 1; 53(6): 886-91. Erratum In: Int J Cancer 1993 July 9; 54(5): 887. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8473047&dopt=Abstract
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Nonmelanomatous skin cancer following cervical, vaginal, and vulvar neoplasms: etiologic association. Author(s): Levi F, Randimbison L, La Vecchia C. Source: Journal of the National Cancer Institute. 1998 October 21; 90(20): 1570-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9790551&dopt=Abstract
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Non-melanotic skin cancer and solar keratoses in Victoria. Author(s): Marks R, Ponsford MW, Selwood TS, Goodman G, Mason G. Source: The Medical Journal of Australia. 1983 December 10-24; 2(12): 619-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6669125&dopt=Abstract
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Non-melanotic skin cancer and solar keratoses in Victoria--clinical studies II. Author(s): Goodman GJ, Marks R, Selwood TS, Ponsford MW, Pakes W. Source: The Australasian Journal of Dermatology. 1984 December; 25(3): 103-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6534368&dopt=Abstract
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Nonmelanotic skin cancer and solar keratoses. The quiet 20th century epidemic. Author(s): Marks R. Source: International Journal of Dermatology. 1987 May; 26(4): 201-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3298089&dopt=Abstract
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Non-solar ultraviolet radiation and the risk of basal and squamous cell skin cancer. Author(s): Bajdik CD, Gallagher RP, Astrakianakis G, Hill GB, Fincham S, McLean DI. Source: British Journal of Cancer. 1996 June; 73(12): 1612-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8664139&dopt=Abstract
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On a possible protective effect of HLA-A11 against skin cancer and keratotic skin lesions in renal transplant recipients. Author(s): Bouwes Bavinck JN, Kootte AM, Van Der Woude FJ, Vandenbroucke JP, Vermeer BJ, Claas FH. Source: The Journal of Investigative Dermatology. 1991 August; 97(2): 269-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1649229&dopt=Abstract
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On call. I learned a lot from your article on melanoma, but I'm puzzled about one point. You suggest using sunscreen, but I read in my newspaper's health column that sunscreens may cause skin cancer. Should I use a sunscreen or not? Author(s): Simon HB. Source: Harvard Men's Health Watch. 2000 December; 5(5): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11114810&dopt=Abstract
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Organization of a specialty clinic to optimize the care of organ transplant recipients at risk for skin cancer. Author(s): Otley CC. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2000 July; 26(7): 709-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10886290&dopt=Abstract
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Overview of radiation-induced skin cancer in humans. Author(s): Shore RE. Source: International Journal of Radiation Biology. 1990 April; 57(4): 809-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1969909&dopt=Abstract
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Overview of skin cancer detection and prevention for the primary care physician. Author(s): Bruce AJ, Brodland DG. Source: Mayo Clinic Proceedings. 2000 May; 75(5): 491-500. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10807078&dopt=Abstract
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Oxidative stress in malignant melanoma and non-melanoma skin cancer. Author(s): Sander CS, Hamm F, Elsner P, Thiele JJ. Source: The British Journal of Dermatology. 2003 May; 148(5): 913-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786821&dopt=Abstract
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Ozone depletion and skin cancer. Author(s): Diffey BL. Source: Bmj (Clinical Research Ed.). 1992 May 2; 304(6835): 1176-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1392804&dopt=Abstract
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p53 codon 72 polymorphism and human papillomavirus associated skin cancer. Author(s): O'Connor DP, Kay EW, Leader M, Atkins GJ, Murphy GM, Mabruk MJ. Source: Journal of Clinical Pathology. 2001 July; 54(7): 539-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11429426&dopt=Abstract
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p53 immunoreactivity in non-melanoma skin cancer from immunosuppressed and immunocompetent individuals: a comparative study of 246 tumours. Author(s): Khorshid SM, Glover MT, Churchill L, McGregor JM, Proby CM. Source: Journal of Cutaneous Pathology. 1996 June; 23(3): 229-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8793657&dopt=Abstract
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p53 mutations as a marker of skin cancer risk: comparison of UVA and UVB effects. Author(s): de Gruijl FR. Source: Experimental Dermatology. 2002; 11 Suppl 1: 37-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444958&dopt=Abstract
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p53 mutations implicate sunlight in post-transplant skin cancer irrespective of human papillomavirus status. Author(s): McGregor JM, Berkhout RJ, Rozycka M, ter Schegget J, Bouwes Bavinck JN, Brooks L, Crook T. Source: Oncogene. 1997 October 2; 15(14): 1737-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9349508&dopt=Abstract
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Pain caused by photodynamic therapy of skin cancer. Author(s): Grapengiesser S, Ericson M, Gudmundsson F, Larko O, Rosen A, Wennberg AM. Source: Clinical and Experimental Dermatology. 2002 September; 27(6): 493-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372093&dopt=Abstract
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Parameters related to oxygen free radicals in human skin: a study comparing healthy epidermis and skin cancer tissue. Author(s): Nogues MR, Giralt M, Cervello I, Del Castillo D, Espeso O, Argany N, Aliaga A, Mallol J. Source: The Journal of Investigative Dermatology. 2002 September; 119(3): 645-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230508&dopt=Abstract
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Parathyroid hormone-related protein and skin cancer. Author(s): Foley PA. Source: The Australasian Journal of Dermatology. 1997 June; 38 Suppl 1: S13-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10994465&dopt=Abstract
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Parental knowledge and practice of primary skin cancer prevention: gaps and solutions. Author(s): Weinstein JM, Yarnold PR, Hornung RL. Source: Pediatric Dermatology. 2001 November-December; 18(6): 473-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11841630&dopt=Abstract
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Participant satisfaction and value in American Academy of Dermatology and American Cancer Society skin cancer screening programs in Massachusetts. Author(s): Geller AC, Halpern AC, Sun T, Oliveria SA, Miller DR, Lew RA, Koh HK. Source: Journal of the American Academy of Dermatology. 1999 April; 40(4): 563-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10188674&dopt=Abstract
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Perfusion therapy for skin cancer. Author(s): Golomb FM. Source: J Dermatol Surg. 1975 December; 1(4): 39-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1083398&dopt=Abstract
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Relationship between p53 codon 72 polymorphism and susceptibility to sunburn and skin cancer. Author(s): McGregor JM, Harwood CA, Brooks L, Fisher SA, Kelly DA, O'nions J, Young AR, Surentheran T, Breuer J, Millard TP, Lewis CM, Leigh IM, Storey A, Crook T. Source: The Journal of Investigative Dermatology. 2002 July; 119(1): 84-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12164929&dopt=Abstract
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Relationship between risk factors, knowledge and preventive behaviour relevant to skin cancer in general practice patients in south Australia. Author(s): Martin RH. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 1995 July; 45(396): 365-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7612341&dopt=Abstract
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Relevance of in vivo models in melanoma skin cancer. Author(s): Setlow RB. Source: Photochemistry and Photobiology. 1996 April; 63(4): 410-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8934751&dopt=Abstract
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Repair of cutaneous defects after skin cancer surgery. Author(s): Schmid MH, Meuli-Simmen C, Hafner J. Source: Recent Results Cancer Res. 2002; 160: 225-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12079217&dopt=Abstract
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Repair of directly and indirectly UV-induced DNA lesions and of DNA doublestrand breaks in cells from skin cancer-prone patients with the disorders dysplastic nevus syndrome or basal cell nevus syndrome. Author(s): Runger TM, Epe B, Moller K, Dekant B, Hellfritsch D. Source: Recent Results Cancer Res. 1997; 143: 337-51. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8912431&dopt=Abstract
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Reports by patients and dermatologists of skin cancer preventive services provided in dermatology offices. Author(s): Polster AM, Lasek RJ, Quinn LM, Chren MM. Source: Archives of Dermatology. 1998 September; 134(9): 1095-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9762020&dopt=Abstract
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Reproducibility of histopathologic diagnosis and classification of non-melanocytic skin cancer: a panel exercise in the framework of the multicenter southern European study HELIOS. Author(s): Wechsler J, Zanetti R, Schrameck C, Rosso S, Pippione M, Linares J, Laurent R, Ortuno G, Boi S, Gafa L, Joris F, Spatz A, Barneon G, Sacerdote C, Sancho-Garnier H; HELIOS Group. Source: Tumori. 2001 March-April; 87(2): 95-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401214&dopt=Abstract
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Research note: the Lions Cancer Institute and the Western Australian Society of Plastic Surgeons skin cancer screening programme. Author(s): Katris P, Crock JG, Gray BN. Source: The Australian and New Zealand Journal of Surgery. 1996 February; 66(2): 1014. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8602803&dopt=Abstract
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Results from a skin cancer screening program in Western Australia. Author(s): Katris P. Source: The Medical Journal of Australia. 1995 November 20; 163(10): 557. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8538531&dopt=Abstract
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Results of annual skin cancer screening. Author(s): Zemtsov A, Tomecki KJ, Dijkstra JW, Hirsh F. Source: Cleve Clin J Med. 1991 January-February; 58(1): 53. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2070516&dopt=Abstract
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Results of radiotherapy for epithelial skin cancer of the pinna: the Princess Margaret Hospital experience, 1982-1993. Author(s): Silva JJ, Tsang RW, Panzarella T, Levin W, Wells W. Source: International Journal of Radiation Oncology, Biology, Physics. 2000 May 1; 47(2): 451-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10802373&dopt=Abstract
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Results of radiotherapy of skin cancer, with special emphasis on treatment failure. Author(s): Shigematsu Y, Webster JH, Bricout P. Source: Radiology. 1966 May; 86(5): 904-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5936102&dopt=Abstract
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Retinoid chemoprevention in patients at high risk for skin cancer. Author(s): DiGiovanna JJ. Source: Medical and Pediatric Oncology. 2001 May; 36(5): 564-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11340613&dopt=Abstract
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Retinoids and interferons in non-melanoma skin cancer. Author(s): Lippman SM, Kalvakolanu DV, Lotan R. Source: The Journal of Investigative Dermatology. Symposium Proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research. 1996 April; 1(2): 219-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9627720&dopt=Abstract
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Retinoids in prevention of skin cancer. Author(s): Moon TE, Levine N, Cartmel B, Bangert JL. Source: Cancer Letters. 1997 March 19; 114(1-2): 203-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9103292&dopt=Abstract
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Retinoids in the management of non-melanoma skin cancer and melanoma. Author(s): Craven NM, Griffiths CE. Source: Cancer Surv. 1996; 26: 267-88. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8783579&dopt=Abstract
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Rising trends in melanoma--an hypothesis concerning sunscreen effectiveness. The Photobiology Committee of the Skin Cancer Foundation. Author(s): Pathak MA, DeLeo VA, Epstein JH, Morison W. Source: Annals of Epidemiology. 1993 July; 3(4): 451. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8275225&dopt=Abstract
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Risk factors associated with the development of skin cancer after liver transplantation. Author(s): Mithoefer AB, Supran S, Freeman RB. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2002 October; 8(10): 939-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12360438&dopt=Abstract
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Risk factors for non-melanomatous skin cancer in Alexandria, Egypt. Author(s): el Khwsky F, Bedwani R, D'Avanzo B, Assaad S, el Shafei Ali A, Mokhtar S, La Vecchia C. Source: International Journal of Cancer. Journal International Du Cancer. 1994 February 1; 56(3): 375-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8314325&dopt=Abstract
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Risk factors for skin cancer in a group of renal transplant recipients. Author(s): Tessari G, Barba A, Chieregato C. Source: Acta Dermato-Venereologica. 1999 September; 79(5): 409-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10494739&dopt=Abstract
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Risk factors of non-melanoma skin cancer in United States veterans patients: a pilot study and review of literature. Author(s): Chuang TY, Brashear R. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 1999 March; 12(2): 126-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10343941&dopt=Abstract
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Risk of basal cell and squamous cell skin cancers after ionizing radiation therapy. For The Skin Cancer Prevention Study Group. Author(s): Karagas MR, McDonald JA, Greenberg ER, Stukel TA, Weiss JE, Baron JA, Stevens MM. Source: Journal of the National Cancer Institute. 1996 December 18; 88(24): 1848-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8961975&dopt=Abstract
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Risk of developing a subsequent nonmelanoma skin cancer in patients with a history of nonmelanoma skin cancer: a critical review of the literature and meta-analysis. Author(s): Marcil I, Stern RS. Source: Archives of Dermatology. 2000 December; 136(12): 1524-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11115165&dopt=Abstract
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Risk of nonmelanoma skin cancer in Italian organ transplant recipients. A registrybased study. Author(s): Naldi L, Fortina AB, Lovati S, Barba A, Gotti E, Tessari G, Schena D, Diociaiuti A, Nanni G, La Parola IL, Masini C, Piaserico S, Peserico A, Cainelli T, Remuzzi G. Source: Transplantation. 2000 November 27; 70(10): 1479-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11118094&dopt=Abstract
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Risk of subsequent basal cell carcinoma and squamous cell carcinoma of the skin among patients with prior skin cancer. Skin Cancer Prevention Study Group. Author(s): Karagas MR, Stukel TA, Greenberg ER, Baron JA, Mott LA, Stern RS. Source: Jama : the Journal of the American Medical Association. 1992 June 24; 267(24): 3305-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1597912&dopt=Abstract
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Risk of subsequent cancer following invasive or in situ squamous cell skin cancer. Author(s): Efird JT, Friedman GD, Habel L, Tekawa IS, Nelson LM. Source: Annals of Epidemiology. 2002 October; 12(7): 469-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377424&dopt=Abstract
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Risk of synchronous and metachronous second nonmelanoma skin cancer when referred for Mohs micrographic surgery. Author(s): Schinstine M, Goldman GD. Source: Journal of the American Academy of Dermatology. 2001 March; 44(3): 497-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11209121&dopt=Abstract
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Role of Bak in UV-induced apoptosis in skin cancer and abrogation by HPV E6 proteins. Author(s): Jackson S, Harwood C, Thomas M, Banks L, Storey A. Source: Genes & Development. 2000 December 1; 14(23): 3065-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11114894&dopt=Abstract
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Role of modern radiotherapy in treating skin cancer. Author(s): Veness M, Richards S. Source: The Australasian Journal of Dermatology. 2003 August; 44(3): 159-66; Quiz 1678. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869039&dopt=Abstract
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Role of rapid imprint cytology in the diagnosis of skin cancer and assessment of adequacy of excision. Author(s): Aryya NC, Khanna S, Shukla HS, Tripathi FM, Shukla VK. Source: Indian J Pathol Microbiol. 1992 April; 35(2): 108-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1483710&dopt=Abstract
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Role of retinoids in skin cancer treatment and prevention. Author(s): Levine N. Source: Journal of the American Academy of Dermatology. 1998 August; 39(2 Pt 3): S626. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9703126&dopt=Abstract
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Role of UVA in the pathogenesis of melanoma and non-melanoma skin cancer. A short review. Author(s): Runger TM. Source: Photodermatology, Photoimmunology & Photomedicine. 1999 December; 15(6): 212-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10599968&dopt=Abstract
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Salvage treatment of recurrent skin cancer of the midface. Author(s): Ampil FL, Nathan CA, Lian TF, Stucker FJ, Hardin JC Jr, Aarstad RF. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2002 December; 25(6): 580-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478003&dopt=Abstract
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Screening for skin cancer. Author(s): Helfand M, Mahon SM, Eden KB, Frame PS, Orleans CT. Source: American Journal of Preventive Medicine. 2001 April; 20(3 Suppl): 47-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11306232&dopt=Abstract
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Screening for skin cancer. Author(s): Ferrini R. Source: American Family Physician. 2002 April 1; 65(7): 1401-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11996425&dopt=Abstract
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Screening for skin cancer: recommendations and rationale. Author(s): US Preventive Services Task Force. Source: American Journal of Preventive Medicine. 2001 April; 20(3 Suppl): 44-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11306231&dopt=Abstract
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Screening for skin cancer: recommendations and rationale. Author(s): U.S. Preventive Services Task Force. Source: The American Journal of Nursing. 2002 May; 102(5): 97, 99, 101; Discussion 103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006861&dopt=Abstract
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Selections from current literature: screening for skin cancer: sense or nonsense? Author(s): Kopes-Kerr CP. Source: Family Practice. 2002 February; 19(1): 112-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11818360&dopt=Abstract
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Seroreactivity to epidermodysplasia verruciformis-related human papillomavirus types is associated with nonmelanoma skin cancer. Author(s): Feltkamp MC, Broer R, di Summa FM, Struijk L, van der Meijden E, Verlaan BP, Westendorp RG, ter Schegget J, Spaan WJ, Bouwes Bavinck JN. Source: Cancer Research. 2003 May 15; 63(10): 2695-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750299&dopt=Abstract
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Should the skin cancer examination be taught in medical school? Author(s): Geller AC, Venna S, Prout M, Miller DR, Demierre MF, Koh HK, Gilchrest BA. Source: Archives of Dermatology. 2002 September; 138(9): 1201-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12224981&dopt=Abstract
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Similarities in sunlight-induced mutational spectra of CpG-methylated transgenes and the p53 gene in skin cancer point to an important role of 5-methylcytosine residues in solar UV mutagenesis. Author(s): You YH, Pfeifer GP. Source: Journal of Molecular Biology. 2001 January 19; 305(3): 389-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11152598&dopt=Abstract
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Sins of the sun. Tools for skin cancer prevention and early detection. Author(s): Burke CC. Source: Adv Nurse Pract. 2000 May; 8(5): 32-6, 38, 45-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11235333&dopt=Abstract
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Skin cancer after X-ray treatment for scalp ringworm. Author(s): Shore RE, Moseson M, Xue X, Tse Y, Harley N, Pasternack BS. Source: Radiation Research. 2002 April; 157(4): 410-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11893243&dopt=Abstract
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Skin cancer and non-Hodgkin's lymphoma as second malignancies. markers of impaired immune function? Author(s): Hemminki K, Jiang Y, Steineck G. Source: European Journal of Cancer (Oxford, England : 1990). 2003 January; 39(2): 223-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509955&dopt=Abstract
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Skin cancer and ozone depletion: the case for global action. Author(s): Mettlin CJ. Source: Journal of Surgical Oncology. 2001 June; 77(2): 76-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11398156&dopt=Abstract
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Skin cancer and ultraviolet-B radiation under the Antarctic ozone hole: southern Chile, 1987-2000. Author(s): Abarca JF, Casiccia CC. Source: Photodermatology, Photoimmunology & Photomedicine. 2002 December; 18(6): 294-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535025&dopt=Abstract
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Skin cancer awareness in suburban employees: a Hispanic perspective. Author(s): Pipitone M, Robinson JK, Camara C, Chittineni B, Fisher SG. Source: Journal of the American Academy of Dermatology. 2002 July; 47(1): 118-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12077590&dopt=Abstract
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Skin cancer control in the primary care setting: are we making any progress? Author(s): Dolan NC. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 2001 May; 16(5): 342-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11359555&dopt=Abstract
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Skin cancer day in Italy: method of referral to open access clinics and tumor prevalence in the examined population. Author(s): Carli P, De Giorgi V, Giannotti B, Seidenari S, Pellacani G, Peris K, Piccolo D, Rubegni P, Andreassi L. Source: Eur J Dermatol. 2003 January-February; 13(1): 76-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609788&dopt=Abstract
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Skin cancer in organ transplant recipients: Epidemiology, pathogenesis, and management. Author(s): Berg D, Otley CC. Source: Journal of the American Academy of Dermatology. 2002 July; 47(1): 1-17; Quiz 18-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12077575&dopt=Abstract
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Skin cancer in the elderly. Author(s): Sachs DL, Marghoob AA, Halpern A. Source: Clinics in Geriatric Medicine. 2001 November; 17(4): 715-38, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11535425&dopt=Abstract
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Skin cancer induced by arsenic in the water. Author(s): Cabrera HN, Gomez ML. Source: Journal of Cutaneous Medicine and Surgery. 2003 March-April; 7(2): 106-11. Epub 2002 November 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447618&dopt=Abstract
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Skin cancer is among the most costly of all cancers to treat for the Medicare population. Author(s): Housman TS, Feldman SR, Williford PM, Fleischer AB Jr, Goldman ND, Acostamadiedo JM, Chen GJ. Source: Journal of the American Academy of Dermatology. 2003 March; 48(3): 425-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637924&dopt=Abstract
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Skin cancer prevention and control. Author(s): Wasserman S. Source: Ncsl Legisbrief. 2003 February; 11(9): 1-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587560&dopt=Abstract
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Skin cancer prevention and detection practices among siblings of patients with melanoma. Author(s): Geller AC, Emmons K, Brooks DR, Zhang Z, Powers C, Koh HK, Sober AJ, Miller DR, Li F, Haluska F, Gilchrest BA. Source: Journal of the American Academy of Dermatology. 2003 October; 49(4): 631-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512908&dopt=Abstract
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Skin cancer prevention and screening: summary of the American College of Preventive Medicine's practice policy statements. Author(s): Hill L, Ferrini RL. Source: Ca: a Cancer Journal for Clinicians. 1998 July-August; 48(4): 232-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9676537&dopt=Abstract
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Skin cancer prevention counseling and clinical practices of pediatricians. Author(s): Gritz ER, Tripp MK, de Moor CA, Eicher SA, Mueller NH, Spedale JH. Source: Pediatric Dermatology. 2003 January-February; 20(1): 16-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558840&dopt=Abstract
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Skin cancer prevention counseling by pharmacists: specific outcomes of an intervention trial. Author(s): Mayer JA, Slymen DJ, Eckhardt L, Rosenberg C, Stepanski BM, Creech L, Palmer RC, Elder JP, Graf G, Anderson ST. Source: Cancer Detection and Prevention. 1998; 22(4): 367-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9674880&dopt=Abstract
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Skin Cancer Prevention Research Receives National Award. Author(s): Glanz K. Source: Hawaii Med J. 2001 May; 60(5): 128, 135. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11432051&dopt=Abstract
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Skin cancer prevention. Author(s): Greinert R. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 2001 April; 10(2): 123-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11330451&dopt=Abstract
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Skin cancer prevention: education and public health issues. Author(s): Mahon SM. Source: Semin Oncol Nurs. 2003 February; 19(1): 52-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12638381&dopt=Abstract
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Skin cancer risk in relation to toenail arsenic concentrations in a US population-based case-control study. Author(s): Karagas MR, Stukel TA, Morris JS, Tosteson TD, Weiss JE, Spencer SK, Greenberg ER. Source: American Journal of Epidemiology. 2001 March 15; 153(6): 559-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11257063&dopt=Abstract
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Skin cancer screening and prevention in the primary care setting: national ambulatory medical care survey 1997. Author(s): Oliveria SA, Christos PJ, Marghoob AA, Halpern AC. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 2001 May; 16(5): 297-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11359547&dopt=Abstract
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Skin cancer screening and surveillance. Author(s): Osborne JE. Source: The British Journal of Dermatology. 2002 May; 146(5): 745-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12000369&dopt=Abstract
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Skin cancer screening by dermatologists: prevalence and barriers. Author(s): Federman DG, Kravetz JD, Kirsner RS. Source: Journal of the American Academy of Dermatology. 2002 May; 46(5): 710-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12004312&dopt=Abstract
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Skin cancer screening. Author(s): Wills M. Source: Physical Therapy. 2002 December; 82(12): 1232-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444882&dopt=Abstract
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Skin cancer surveillance in renal transplant recipients: questionnaire survey of current UK practice. Author(s): Harden PN, Reece SM, Fryer AA, Smith AG, Ramsay HM. Source: Bmj (Clinical Research Ed.). 2001 September 15; 323(7313): 600-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11557706&dopt=Abstract
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Skin cancer update. Author(s): Franz R. Source: Dermatology Nursing / Dermatology Nurses' Association. 2001 June; 13(3): 236. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11917462&dopt=Abstract
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Skin cancer update. Treatment alternatives for basal-cell and squamous-cell carcinoma. Author(s): Vine JE. Source: N J Med. 2001 May; 98(5): 35-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11381714&dopt=Abstract
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Skin cancer. Author(s): Buchanan PJ. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 2001 July 25-31; 15(45): 45-52; Quiz 54-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12212388&dopt=Abstract
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The first 15 years of the American Academy of Dermatology skin cancer screening programs: 1985-1999. Author(s): Geller AC, Zhang Z, Sober AJ, Halpern AC, Weinstock MA, Daniels S, Miller DR, Demierre MF, Brooks DR, Gilchrest BA. Source: Journal of the American Academy of Dermatology. 2003 January; 48(1): 34-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522368&dopt=Abstract
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The prevalence of human papillomavirus DNA in benign keratotic skin lesions of renal transplant recipients with and without a history of skin cancer is equally high: a clinical study to assess risk factors for keratotic skin lesions and skin cancer. Author(s): de Jong-Tieben LM, Berkhout RJ, ter Schegget J, Vermeer BJ, de Fijter JW, Bruijn JA, Westendorp RG, Bouwes Bavinck JN. Source: Transplantation. 2000 January 15; 69(1): 44-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10653378&dopt=Abstract
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Too much sun? John McCain's second bout with melanoma reminds all of us to take skin cancer seriously. Author(s): Gorman C. Source: Time. 2000 August 28; 156(9): 65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11066580&dopt=Abstract
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Toward optimal health: the experts respond to skin cancer. Interview by Jodi Godfrey Meisler, M.S., R.D. Author(s): Rigel D, Skouge J. Source: Journal of Women's Health & Gender-Based Medicine. 1999 June; 8(5): 593-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10839643&dopt=Abstract
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Trends in the incidence of non-melanoma skin cancer in Slovakia, 1978-1995. Author(s): Plesko I, Severi G, Obsitnikova A, Boyle P. Source: Neoplasma. 2000; 47(3): 137-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11043834&dopt=Abstract
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Two-week skin cancer referrals. Author(s): Morgan C, Robertshaw H, Cooper H, Keohane S. Source: Clinical and Experimental Dermatology. 2002 March; 27(2): 164. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952715&dopt=Abstract
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Ultrastructural studies on the behaviour of macrophages in the course of X-ray therapy of human skin cancer. Author(s): Vorbrodt A, Hliniak A, Krzyzowska-Gruca S, Gruca S. Source: Acta Histochemica. 1972; 43(2): 270-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4628783&dopt=Abstract
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Ultraviolet exposure and skin cancer response. Author(s): Green AE. Source: American Journal of Epidemiology. 1978 April; 107(4): 277-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=645696&dopt=Abstract
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Ultraviolet radiation and skin cancer in man. Author(s): Urbach F. Source: Preventive Medicine. 1980 March; 9(2): 227-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7383989&dopt=Abstract
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Ultraviolet radiation and skin cancer in mice and men: accumulation of effect and uncertainty of prediction. Author(s): Blum HF. Source: Natl Cancer Inst Monogr. 1978 December; (50): 11-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=753969&dopt=Abstract
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Ultraviolet radiation and skin cancer of humans. Author(s): Urbach F. Source: Journal of Photochemistry and Photobiology. B, Biology. 1997 August; 40(1): 3-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9301039&dopt=Abstract
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Ultraviolet radiation and skin cancer: in mice and men. Author(s): Blum HF. Source: Photochemistry and Photobiology. 1976 September; 24(3): 249-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=981338&dopt=Abstract
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Ultraviolet radiation and skin cancer--keep your top on? Author(s): Strong AM. Source: The British Journal of Dermatology. 1994 November; 131(5): 739-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7999623&dopt=Abstract
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Ultraviolet radiation and the development of non-melanoma and melanoma skin cancer: clinical and experimental evidence. Author(s): Pathak MA. Source: Skin Pharmacol. 1991; 4 Suppl 1: 85-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1764252&dopt=Abstract
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Ultraviolet radiation at high latitudes and the risk of skin cancer. Author(s): Henriksen K, Stamnes K, Volden G, Falk ES. Source: Photodermatol. 1989 June; 6(3): 110-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2762201&dopt=Abstract
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Ultraviolet radiation, Langerhans' cells, and skin cancer. Conspiracy and failure. Author(s): Cruz PD Jr, Bergstresser PR. Source: Archives of Dermatology. 1989 July; 125(7): 975-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2491413&dopt=Abstract
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Ultraviolet wavelength factors in solar radiation and skin cancer. Author(s): Freeman RG, Hudson HT, Carnes MA. Source: International Journal of Dermatology. 1970 July-September; 9(3): 232-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5476384&dopt=Abstract
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Ultraviolet-light induced p53 mutational spectrum in yeast is indistinguishable from p53 mutations in human skin cancer. Author(s): Inga A, Scott G, Monti P, Aprile A, Abbondandolo A, Burns PA, Fronza G. Source: Carcinogenesis. 1998 May; 19(5): 741-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9635858&dopt=Abstract
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Ultraviolet-radiation and skin cancer. Effect of an ozone layer depletion. Author(s): Henriksen T, Dahlback A, Larsen SH, Moan J. Source: Photochemistry and Photobiology. 1990 May; 51(5): 579-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2367555&dopt=Abstract
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Urocanic acid isomers in patients with non-melanoma skin cancer. Author(s): De Simone C, Masini C, Cattaruzza MS, Guerriero C, Cerimele D, Norval M. Source: The British Journal of Dermatology. 2001 April; 144(4): 858-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11298549&dopt=Abstract
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Use of a radon mould technique for skin cancer: results from the Peter MacCallum Cancer Institute (1975-1984). Author(s): Ashby MA, Pacella JA, de Groot R, Ainslie J. Source: The British Journal of Radiology. 1989 July; 62(739): 608-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2758248&dopt=Abstract
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Use of nonphysician health care providers for skin cancer screening in the primary care setting. Author(s): Oliveria SA, Altman JF, Christos PJ, Halpern AC. Source: Preventive Medicine. 2002 March; 34(3): 374-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11902855&dopt=Abstract
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Using ecological data to estimate a regression model for individual data: the association between arsenic in drinking water and incidence of skin cancer. Author(s): Guo HR, Lipsitz SR, Hu H, Monson RR. Source: Environmental Research. 1998 November; 79(2): 82-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9841806&dopt=Abstract
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Using health communications for primary prevention of skin cancer: CDC's Choose Your Cover campaign. Author(s): Jorgensen CM, Wayman J, Green C, Gelb CA. Source: Journal of Women's Health & Gender-Based Medicine. 2000 June; 9(5): 471-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10883937&dopt=Abstract
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Using nurse practitioners for skin cancer screening: a pilot study. Author(s): Oliveria SA, Nehal KS, Christos PJ, Sharma N, Tromberg JS, Halpern AC. Source: American Journal of Preventive Medicine. 2001 October; 21(3): 214-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11567843&dopt=Abstract
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UV and skin cancer: specific p53 gene mutation in normal skin as a biologically relevant exposure measurement. Author(s): Nakazawa H, English D, Randell PL, Nakazawa K, Martel N, Armstrong BK, Yamasaki H. Source: Proceedings of the National Academy of Sciences of the United States of America. 1994 January 4; 91(1): 360-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8278394&dopt=Abstract
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UV mutagenic photoproducts in Escherichia coli and human cells: a molecular genetics perspective on human skin cancer. Author(s): Brash DE. Source: Photochemistry and Photobiology. 1988 July; 48(1): 59-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3064116&dopt=Abstract
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UV protection and skin cancer. Author(s): Dummer R, Maier T. Source: Recent Results Cancer Res. 2002; 160: 7-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12079240&dopt=Abstract
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UVB-induced cyclobutane pyrimidine dimer frequency correlates with skin cancer mutational hotspots in p53. Author(s): Drouin R, Therrien JP. Source: Photochemistry and Photobiology. 1997 November; 66(5): 719-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9383997&dopt=Abstract
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UVB-induced decrease of p16/CDKN2A expression in skin cancer patients. Author(s): Krahn G, Leiter U, Udart M, Kaskel P, Peter RU. Source: Pigment Cell Research / Sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society. 2001 June; 14(3): 201-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11434568&dopt=Abstract
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UV-induced DNA damage, repair, mutations and oncogenic pathways in skin cancer. Author(s): de Gruijl FR, van Kranen HJ, Mullenders LH. Source: Journal of Photochemistry and Photobiology. B, Biology. 2001 October; 63(1-3): 19-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684448&dopt=Abstract
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UV-induced mutations and skin cancer: how important is the link? Author(s): Bridges BA. Source: Mutation Research. 1998 November 9; 422(1): 23-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9920425&dopt=Abstract
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UV-induced skin cancer in a hairless mouse model. Author(s): de Gruijl FR, Forbes PD. Source: Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology. 1995 July; 17(7): 651-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7646487&dopt=Abstract
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Value of health promotion clinic in detection of non-melanoma skin cancer. Author(s): Jones R. Source: The British Journal of Dermatology. 1994 September; 131(3): 447. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7918021&dopt=Abstract
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Variability of skin cancer registration practice in the United Kingdom. Author(s): Maudsley G, Williams EM. Source: Journal of Epidemiology and Community Health. 1997 June; 51(3): 337-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9229069&dopt=Abstract
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Variations of the pursestring suture in skin cancer reconstruction. Author(s): Harrington AC, Montemarano A, Welch M, Farley M. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 1999 April; 25(4): 277-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10417582&dopt=Abstract
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Viral infections in kidney transplant recipients: lack of correlation with skin cancer. Author(s): Kelly GE, Sheil AG, Murphy A, Tayler R. Source: Transplantation Proceedings. 1985 April; 17(2): 1689-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2984812&dopt=Abstract
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Welding and non-melanoma skin cancer. Author(s): Currie CL, Monk BE. Source: Clinical and Experimental Dermatology. 2000 January; 25(1): 28-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10671966&dopt=Abstract
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What do children aged 5 to 11 years old know about the sun and skin cancer? The practical difficulties of international collaborative research when analysis of language is involved. Author(s): Newton Bishop JA, Collins M, Hughes BR, Altman DG, Bergman W, Breitbart EW, de Stavola B, Elvers H, Gylling F, Koopman M, Marks R, Martin M, Martin M, Murphy G, Osterlind A, Wetton N. Source: Melanoma Research. 1997 October; 7(5): 428-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9429227&dopt=Abstract
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What do Danes know about naevi, skin cancer and melanoma? Experience from a dermatological out-patient clinic. Author(s): Osterlind A, Stender IM, Heinavaara S. Source: Melanoma Research. 1997 February; 7(1): 69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9067968&dopt=Abstract
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What do young people think about the dangers of sunbathing, skin cancer and sunbeds? A questionnaire survey among Italians. Author(s): Monfrecola G, Fabbrocini G, Posteraro G, Pini D. Source: Photodermatology, Photoimmunology & Photomedicine. 2000 February; 16(1): 15-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10721859&dopt=Abstract
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What lessons can be learned for cancer registration quality assurance from data users? Skin cancer as an example. Author(s): Maudsley G, Williams EM. Source: International Journal of Epidemiology. 1999 October; 28(5): 809-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10597975&dopt=Abstract
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Who comes to a skin cancer screening--and why? Author(s): McMichael AJ, Jackson S. Source: N C Med J. 1998 September-October; 59(5): 294-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9785903&dopt=Abstract
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Worthwhile efforts for skin cancer prevention. Author(s): Tetrault G. Source: Dermatology Nursing / Dermatology Nurses' Association. 1993 April; 5(2): 102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8507531&dopt=Abstract
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Xeroderma pigmentosum and the role of UV-induced DNA damage in skin cancer. Author(s): van Steeg H, Kraemer KH. Source: Molecular Medicine Today. 1999 February; 5(2): 86-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10200950&dopt=Abstract
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Xeroderma pigmentosum, photosensitivity, and risk for skin cancer. Author(s): Johnson JA. Source: The Journal of Investigative Dermatology. 1990 September; 95(3): 366. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2384695&dopt=Abstract
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Xeroderma pigmentosum. Defective DNA repair causes skin cancer and neurodegeneration. Author(s): Robbins JH. Source: Jama : the Journal of the American Medical Association. 1988 July 15; 260(3): 384-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3379749&dopt=Abstract
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X-ray therapy of skin cancer: evaluation of a "standardized" method for treating basal-cell epitheliomas. Author(s): Bart RS, Kopf AW, Petratos MA. Source: Proc Natl Cancer Conf. 1970; 6: 559-69. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5458122&dopt=Abstract
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X-ray treatment of skin cancer. Short fractionation technique. Author(s): Shelmire DS. Source: Cutis; Cutaneous Medicine for the Practitioner. 1982 April; 29(4): 345-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7083910&dopt=Abstract
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Yield from total skin examination and effectiveness of skin cancer awareness program. Findings in 874 new dermatology patients. Author(s): Lee G, Massa MC, Welykyj S, Choo J, Greaney V. Source: Cancer. 1991 January 1; 67(1): 202-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1985718&dopt=Abstract
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Zinc, carotene, and retinol in melanoma and non-melanoma skin cancer. Author(s): Siu TO, Basu T, Jerry LM. Source: In Vivo. 1991 January-February; 5(1): 65-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1932628&dopt=Abstract
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Zosteriform metastatic skin cancer: report of three cases and review of the literature. Author(s): Kikuchi Y, Matsuyama A, Nomura K. Source: Dermatology (Basel, Switzerland). 2001; 202(4): 336-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11455149&dopt=Abstract
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CHAPTER 2. NUTRITION AND SKIN CANCER Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and skin cancer.
Finding Nutrition Studies on Skin 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 “skin 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 information is typical of that found when using the “Full IBIDS Database” to search for “skin cancer” (or a synonym): •
A dose-response analysis of skin cancer from inorganic arsenic in drinking water. Author(s): Research Triangle Institute, Research Triangle Park, North Carolina 27709. Source: Brown, K G Boyle, K E Chen, C W Gibb, H J Risk-Anal. 1989 December; 9(4): 519-28 0272-4332
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Advances in the treatment of nonmelanoma skin cancer. Author(s): Northwestern University Medical School, Chicago, Illinois. Source: Robinson, J K Dermatol-Clin. 1991 October; 9(4): 757-64 0733-8635
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An approach to studying the possible effects of carotenoids in skin cancer prevention. Source: Greenberg, E.R. Vitamins and cancer prevetion / editors, Stewart A Laidlaw, Marin E Swendseid. New York : Wiley-Liss, c1991.. page 1-14. ISBN: 0471560669
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An approach towards understanding the genesis of sunlight-induced skin cancer. Author(s): Biophysics Division, Saha Institute of Nuclear Physics, Calcutta. Source: Chatterjee, S N Agarwal, S Bose, B Indian-J-Biochem-Biophys. 1990 August; 27(4): 254-63 0301-1208
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An ecologic study of skin cancer and environmental arsenic exposure. Author(s): ENSR Health Sciences, Alameda, CA 94501. Source: Wong, O Whorton, M D Foliart, D E Lowengart, R Int-Arch-Occup-EnvironHealth. 1992; 64(4): 235-41 0340-0131
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Antioxidants in chemoprevention of skin cancer. Author(s): Department of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA. Source: Ahmad, N Katiyar, S K Mukhtar, H Curr-Probl-Dermatol. 2001; 29: 128-39 00702064
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Chemoprevention of human skin cancer. Author(s): Arizona Cancer Center, University of Arizona, 1515, North Campbell Avenue, Tucson 85724, USA.
[email protected] Source: Einspahr, J G Stratton, S P Bowden, G T Alberts, D S Crit-Rev-Oncol-Hematol. 2002 March; 41(3): 269-85 1040-8428
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Chemoprevention of skin cancer in xeroderma pigmentosum. Author(s): Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. Source: Kraemer, K H DiGiovanna, J J Peck, G L J-Dermatol. 1992 November; 19(11): 715-8 0385-2407
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Does sunscreen block the skin's ability to make vitamin D? If so, how can I get enough of this vitamin without raising my risk of skin cancer? Source: Holick, Michael Health-News. 2002 July; 8(7): 12 1081-5880
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Expression of a retinoid-inducible tumor suppressor, Tazarotene-inducible gene-3, is decreased in psoriasis and skin cancer. Author(s): Department of Internal Medical Specialties, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
[email protected] Source: Duvic, M Helekar, B Schulz, C Cho, M DiSepio, D Hager, C DiMao, D Hazarika, P Jackson, B Breuer McHam, J Young, J Clayman, G Lippman, S M Chandraratna, R A Robinson, N A Deucher, A Eckert, R L Nagpal, S Clin-Cancer-Res. 2000 August; 6(8): 3249-59 1078-0432
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Feasibility study to relate arsenic in drinking water to skin cancer in the United States. Source: Andelman, J.B. Barnett, M. Environmental epidemiology / [edited by] Frederick C. Kopfler, Gunther F. Craun. Chelsea, Mich. : Lewis Publishers, c1986. page 89-107. ISBN: 0873710738
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Flavonoid antioxidant silymarin and skin cancer. Author(s): Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO 80262, USA. Source: Singh, R P Agarwal, R Antioxid-Redox-Signal. 2002 August; 4(4): 655-63 15230864
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Home treatment of skin cancer and solar keratoses. Source: Green, A C Beardmore, G L Australas-J-Dermatol. 1988; 29(3): 127-30 0004-8380
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Low-dose retinoid therapy for chemoprophylaxis of skin cancer in renal transplant recipients. Author(s): Department of Dermatology, Beaumont Hospital, Dublin, Ireland.
[email protected] Source: Gibson, G E O'Grady, A Kay, E W Murphy, G M J-Eur-Acad-Dermatol-Venereol. 1998 January; 10(1): 42-7 0926-9959
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Modulation of biologic endpoints by topical difluoromethylornithine (DFMO), in subjects at high-risk for nonmelanoma skin cancer. Author(s): Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724, USA.
[email protected] Source: Einspahr, Janine G Nelson, Mark A Saboda, Kathylynn Warneke, James Bowden, G Timothy Alberts, David S Clin-Cancer-Res. 2002 Jan; 8(1): 149-55 1078-0432
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Multidisciplinary treatment of facial skin cancer. Author(s): Department of Otolaryngology, University of Texas Medical Branch, Galveston 77550. Source: Calhoun, K H Wagner, R F Tex-Med. 1991 December; 87(12): 64-9 0040-4470
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Nonmelanoma skin cancer and plasma selenium: a prospective cohort study. Source: Clark, L.C. Graham, G.F. Bray, J. Turnbull, B.W. Hulka, B.S. Shy, C.M. 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 1122-1134. ISBN: 0442221088
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Nonmelanoma skin cancer. Author(s): Department of Dermatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
[email protected] Source: Nguyen, Tri H Ho, Diana Quynh Dao Curr-Treat-Options-Oncol. 2002 June; 3(3): 193-203 1527-2729
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Novel approaches to chemoprevention of skin cancer. Author(s): Department of Dermatology, Columbia Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA. Source: Bickers, D R Athar, M J-Dermatol. 2000 November; 27(11): 691-5 0385-2407
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Phase II and biologic study of interferon alfa, retinoic acid, and cisplatin in advanced squamous skin cancer. Author(s): Department of Thoracic/Head and Neck Medical Oncology, Diagnostic Imaging, Biostatistics, Head and Neck Surgery, and Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4095, USA.
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Source: Shin, Dong M Glisson, Bonnie S Khuri, Fadlo R Clifford, John L Clayman, Gary Benner, Steven E Forastiere, Arlene A Ginsberg, Lawrence Liu, Diane Lee, J Jack Myers, Jeffrey Goepfert, Helmuth Lotan, Reuben Hong, Waun Ki Lippman, Scott M J-ClinOncol. 2002 January 15; 20(2): 364-70 0732-183X •
Phase II clinical trials with rhizoxin in breast cancer and melanoma. The EORTC Early Clinical Trials Group. Author(s): I. Department of Medicine, Klinikum rechts, Isar der Technischen Universitat Munchen, Germany. Source: Hanauske, A R Catimel, G Aamdal, S ten Bokkel Huinink, W Paridaens, R Pavlidis, N Kaye, S B te Velde, A Wanders, J Verweij, J Br-J-Cancer. 1996 February; 73(3): 397-9 0007-0920
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Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. European Organization for Research and Treatment of Cancer Malignant Melanoma Cooperative Group Protocol 18832, the World Health Organization Melanoma Program Trial 15, and the North American Perfusion Group Southwest Oncology Group-8593. Author(s): Department of Surgical Oncology, University Hospital, Groningen, The Netherlands. Source: Koops, H S Vaglini, M Suciu, S Kroon, B B Thompson, J F Gohl, J Eggermont, A M Di Filippo, F Krementz, E T Ruiter, D Lejeune, F J J-Clin-Oncol. 1998 September; 16(9): 2906-12 0732-183X
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Retinoid chemoprevention in patients at high risk for skin cancer. Author(s): Division of Dermatopharmacology, Department of Dermatology, Brown University School of Medicine and Rhode Island Hospital, Providence, Rhode Island 02903, USA.
[email protected] Source: DiGiovanna, J J Med-Pediatr-Oncol. 2001 May; 36(5): 564-7 0098-1532
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Signal transduction pathways: targets for chemoprevention of skin cancer. Author(s): Hormel Institute, University of Minnesota, Austin 55912, USA. Source: Bode A, M Dong, Z Lancet-Oncol. 2000 November; 1: 181-8 1470-2045
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Skin cancer and chromosomal aberrations induced by ultraviolet radiation. Evidence for lack of correlation in xeroderma pigmentosum variant and group E patients. Author(s): Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892. Source: Seguin, L R Ganges, M B Tarone, R E Robbins, J H Cancer-Genet-Cytogenet. 1992 June; 60(2): 111-6 0165-4608
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Skin cancer in blacks in the United States. Author(s): Howard University College of Medicine, Washington, D.C. Source: Halder, R M Bang, K M Dermatol-Clin. 1988 July; 6(3): 397-405 0733-8635
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Tanning beds and skin cancer: artificial sun + old sol = real risk. Author(s): Department of Dermatology and Cutaneous Surgery, University of Miami, School of Medicine, Florida, USA. Source: Spencer, J M Amonette, R Clin-Dermatol. 1998 Jul-August; 16(4): 487-501 0738081X
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The results of topical application of 13-cis-retinoic acid on basal cell carcinoma. A correlation of the clinical effect with histopathological examination and serum retinol level. Author(s): Department of General and Thoracic Surgery, Institute of Surgery, School of Medicine, Warsaw, Poland.
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Source: Sankowski, A Janik, P Jeziorska, M Swietochowska, B Ciesla, W Malek, A Przybyszewska, M Neoplasma. 1987; 34(4): 485-9 0028-2685 •
The use of retinoids in the prevention and treatment of skin cancer. Author(s): Department of Biochemistry and Molecular Biology, Joan C Edwards School of Medicine, Marshall University, 1542 Spring Valley Drive, Huntington, West Virginia 25704, USA.
[email protected] Source: Niles, R M Expert-Opin-Pharmacother. 2002 March; 3(3): 299-303 1465-6566
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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WebMDHealth: 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 skin 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): •
Vitamins Vitamin A Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10066,00.html Vitamin D Alternative names: Calciferol, Calcitrol, Cholecalciferol, Erocalciferol Source: Integrative Medicine Communications; www.drkoop.com
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Minerals Cisplatin Source: Healthnotes, Inc. www.healthnotes.com Selenium Source: Prima Communications, Inc.www.personalhealthzone.com Tretinoin Source: Healthnotes, Inc. www.healthnotes.com
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Food and Diet Cancer Prevention and Diet Source: Healthnotes, Inc. www.healthnotes.com Omega-6 Fatty Acids Source: Integrative Medicine Communications; www.drkoop.com Tea Source: Healthnotes, Inc. www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND SKIN CANCER Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to skin 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 skin 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 “skin 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 skin cancer: •
A case of phenacetin-induced skin cancer in Hong Kong. Author(s): Leung JS. Source: Hong Kong Medical Journal = Xianggang Yi Xue Za Zhi / Hong Kong Academy of Medicine. 2001 September; 7(3): 323-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11590281&dopt=Abstract
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A randomized, 12-year primary-prevention trial of beta carotene supplementation for nonmelanoma skin cancer in the physician's health study. Author(s): Frieling UM, Schaumberg DA, Kupper TS, Muntwyler J, Hennekens CH. Source: Archives of Dermatology. 2000 February; 136(2): 179-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10677093&dopt=Abstract
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A vehicle for photodynamic therapy of skin cancer: influence of dimethylsulphoxide on 5-aminolevulinic acid in vitro cutaneous permeation and in vivo protoporphyrin
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IX accumulation determined by confocal microscopy. Author(s): De Rosa FS, Marchetti JM, Thomazini JA, Tedesco AC, Bentley MV. Source: Journal of Controlled Release : Official Journal of the Controlled Release Society. 2000 April 3; 65(3): 359-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10699294&dopt=Abstract •
Antioxidants in chemoprevention of skin cancer. Author(s): Ahmad N, Katiyar SK, Mukhtar H. Source: Current Problems in Dermatology. 2001; 29: 128-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11225193&dopt=Abstract
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Antitumor activity of Virulizin, a novel biological response modifier (BRM) in a panel of human pancreatic cancer and melanoma xenografts. Author(s): Feng N, Jin H, Wang M, Du C, Wright JA, Young AH. Source: Cancer Chemotherapy and Pharmacology. 2003 March; 51(3): 247-55. Epub 2003 March 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655444&dopt=Abstract
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Basal cell carcinoma in a blue-fronted amazon parrot (Amazona aestiva). Author(s): Tell LA, Woods L, Mathews KG. Source: Avian Dis. 1997 July-September; 41(3): 755-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9356728&dopt=Abstract
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Basal cell carcinoma in young women: an evaluation of the association of tanning bed use and smoking. Author(s): Boyd AS, Shyr Y, King LE Jr. Source: Journal of the American Academy of Dermatology. 2002 May; 46(5): 706-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12004311&dopt=Abstract
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Basal cell carcinoma on nickel dermatitis after leech applying. Author(s): Shamsaddini S, Dabiri S. Source: East Mediterr Health J. 2000 January; 6(1): 197-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11370335&dopt=Abstract
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Chemoprevention of basal cell carcinomas in the ptc1+/- mouse--green and black tea. Author(s): Hebert JL, Khugyani F, Athar M, Kopelovich L, Epstein EH Jr, Aszterbaum M. Source: Skin Pharmacology and Applied Skin Physiology. 2001 November-December; 14(6): 358-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11598435&dopt=Abstract
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Chemoprevention of human skin cancer. Author(s): Einspahr JG, Stratton SP, Bowden GT, Alberts DS.
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Source: Critical Reviews in Oncology/Hematology. 2002 March; 41(3): 269-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880204&dopt=Abstract •
Chemoprevention of nonmelanoma skin cancer: experience with a polyphenol from green tea. Author(s): Linden KG, Carpenter PM, McLaren CE, Barr RJ, Hite P, Sun JD, Li KT, Viner JL, Meyskens FL. Source: Recent Results Cancer Res. 2003; 163: 165-71; Discussion 264-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12903852&dopt=Abstract
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Chemoprevention of skin cancer through natural agents. Author(s): Gupta S, Mukhtar H. Source: Skin Pharmacology and Applied Skin Physiology. 2001 November-December; 14(6): 373-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11598437&dopt=Abstract
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Chemoprevention of ultraviolet radiation-induced skin cancer. Author(s): Ley RD, Reeve VE. Source: Environmental Health Perspectives. 1997 June; 105 Suppl 4: 981-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9255591&dopt=Abstract
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Consequences of using escharotic agents as primary treatment for nonmelanoma skin cancer. Author(s): McDaniel S, Goldman GD. Source: Archives of Dermatology. 2002 December; 138(12): 1593-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472348&dopt=Abstract
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Coping with melanoma--ten strategies that promote psychological adjustment. Author(s): Kneier AW. Source: The Surgical Clinics of North America. 2003 April; 83(2): 417-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744617&dopt=Abstract
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Cyclooxygenase-2 expression in murine and human nonmelanoma skin cancers: implications for therapeutic approaches. Author(s): An KP, Athar M, Tang X, Katiyar SK, Russo J, Beech J, Aszterbaum M, Kopelovich L, Epstein EH Jr, Mukhtar H, Bickers DR. Source: Photochemistry and Photobiology. 2002 July; 76(1): 73-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126310&dopt=Abstract
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Dietary factors in the prevention and treatment of nonmelanoma skin cancer and melanoma. Author(s): Bialy TL, Rothe MJ, Grant-Kels JM.
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Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2002 December; 28(12): 1143-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472495&dopt=Abstract •
Differential responses of skin cancer-chemopreventive agents silibinin, quercetin, and epigallocatechin 3-gallate on mitogenic signaling and cell cycle regulators in human epidermoid carcinoma A431 cells. Author(s): Bhatia N, Agarwal C, Agarwal R. Source: Nutrition and Cancer. 2001; 39(2): 292-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11759294&dopt=Abstract
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Does daily use of sunscreen or beta-carotene supplements prevent skin cancer in healthy adults? Author(s): Del Mar C. Source: The Western Journal of Medicine. 2000 November; 173(5): 332. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11069872&dopt=Abstract
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Effect of naturally occurring allyl and phenyl isothiocyanates in the inhibition of experimental pulmonary metastasis induced by B16F-10 melanoma cells. Author(s): Manesh C, Kuttan G. Source: Fitoterapia. 2003 June; 74(4): 355-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781806&dopt=Abstract
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Effect of retinol in preventing squamous cell skin cancer in moderate-risk subjects: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Study Group. Author(s): Moon TE, Levine N, Cartmel B, Bangert JL, Rodney S, Dong Q, Peng YM, Alberts DS. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 1997 November; 6(11): 949-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9367069&dopt=Abstract
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Flavonoid antioxidant silymarin and skin cancer. Author(s): Singh RP, Agarwal R. Source: Antioxidants & Redox Signalling. 2002 August; 4(4): 655-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230878&dopt=Abstract
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Genetic epidemiology of melanoma. Author(s): Bataille V.
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Source: European Journal of Cancer (Oxford, England : 1990). 2003 July; 39(10): 1341-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826035&dopt=Abstract •
Investigation of the growth and metastasis of malignant melanoma in a murine model: the role of supplemental vitamin A. Author(s): Weinzweig J, Tattini C, Lynch S, Zienowicz R, Weinzweig N, Spangenberger A, Edstrom L. Source: Plastic and Reconstructive Surgery. 2003 July; 112(1): 152-8; Discussion 159-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832888&dopt=Abstract
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L-[1-11C]-tyrosine PET to evaluate response to hyperthermic isolated limb perfusion for locally advanced soft-tissue sarcoma and skin cancer. Author(s): van Ginkel RJ, Kole AC, Nieweg OE, Molenaar WM, Pruim J, Koops HS, Vaalburg W, Hoekstra HJ. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1999 February; 40(2): 262-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10025833&dopt=Abstract
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Modulation of mitogen-activated protein kinase activation and cell cycle regulators by the potent skin cancer preventive agent silymarin. Author(s): Zi X, Agarwal R. Source: Biochemical and Biophysical Research Communications. 1999 September 24; 263(2): 528-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10491326&dopt=Abstract
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Novel approaches to chemoprevention of skin cancer. Author(s): Bickers DR, Athar M. Source: The Journal of Dermatology. 2000 November; 27(11): 691-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11138532&dopt=Abstract
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Online support group helps patients live with, learn more about the rare skin cancer CTCL-MF. Author(s): Lamberg L. Source: Jama : the Journal of the American Medical Association. 1997 May 14; 277(18): 1422-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9145700&dopt=Abstract
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Paclitaxel encapsulated in cationic liposomes diminishes tumor angiogenesis and melanoma growth in a “humanized” SCID mouse model. Author(s): Kunstfeld R, Wickenhauser G, Michaelis U, Teifel M, Umek W, Naujoks K, Wolff K, Petzelbauer P.
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Source: The Journal of Investigative Dermatology. 2003 March; 120(3): 476-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603862&dopt=Abstract •
Photodynamic therapy of superficial basal cell carcinoma with 5-aminolevulinic acid with dimethylsulfoxide and ethylendiaminetetraacetic acid: a comparison of two light sources. Author(s): Soler AM, Angell-Petersen E, Warloe T, Tausjo J, Steen HB, Moan J, Giercksky KE. Source: Photochemistry and Photobiology. 2000 June; 71(6): 724-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10857368&dopt=Abstract
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Preformulation study of epigallocatechin gallate, a promising antioxidant for topical skin cancer prevention. Author(s): Proniuk S, Liederer BM, Blanchard J. Source: Journal of Pharmaceutical Sciences. 2002 January; 91(1): 111-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11782902&dopt=Abstract
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Preventive effect of antioxidant on ultraviolet-induced skin cancer in mice. Author(s): Ichihashi M, Ahmed NU, Budiyanto A, Wu A, Bito T, Ueda M, Osawa T. Source: Journal of Dermatological Science. 2000 March; 23 Suppl 1: S45-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10764992&dopt=Abstract
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Protection by black tea and green tea against UVB and UVA + B induced skin cancer in hairless mice. Author(s): Record IR, Dreosti IE. Source: Mutation Research. 1998 November 9; 422(1): 191-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9920445&dopt=Abstract
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Protection by tea against UV-A + B-induced skin cancers in hairless mice. Author(s): Record IR, Dreosti IE. Source: Nutrition and Cancer. 1998; 32(2): 71-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9919614&dopt=Abstract
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Psychological adjustment to the melanoma experience. Author(s): Boyle DA. Source: Semin Oncol Nurs. 2003 February; 19(1): 70-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12638383&dopt=Abstract
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Signal transduction pathways: targets for chemoprevention of skin cancer. Author(s): Bode AM, Dong Z.
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Source: The Lancet Oncology. 2000 November; 1: 181-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11905657&dopt=Abstract •
Skin cancer and climatotherapy in psoriasis. Author(s): Even-Paz Z, Efron D. Source: The British Journal of Dermatology. 2001 January; 144(1): 202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11167717&dopt=Abstract
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Skin cancer chemoprevention. Author(s): Mukhtar H, Agarwal R. Source: The Journal of Investigative Dermatology. Symposium Proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research. 1996 April; 1(2): 209-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9627718&dopt=Abstract
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Skin cancer chemoprevention: strategies to save our skin. Author(s): Einspahr JG, Bowden GT, Alberts DS. Source: Recent Results Cancer Res. 2003; 163: 151-64; Discussion 264-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12903851&dopt=Abstract
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Skin cancer chemopreventive effects of a flavonoid antioxidant silymarin are mediated via impairment of receptor tyrosine kinase signaling and perturbation in cell cycle progression. Author(s): Ahmad N, Gali H, Javed S, Agarwal R. Source: Biochemical and Biophysical Research Communications. 1998 June 18; 247(2): 294-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9642119&dopt=Abstract
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Skin cancer in patients with psoriasis-many intertwined risk factors. Author(s): Murphy GM. Source: The British Journal of Dermatology. 1999 December; 141(6): 1001-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10606842&dopt=Abstract
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Successful treatment of an intractable case of hereditary basal cell carcinoma syndrome with paclitaxel. Author(s): El Sobky RA, Kallab AM, Dainer PM, Jillella AP, Lesher JL Jr. Source: Archives of Dermatology. 2001 June; 137(6): 827-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11405789&dopt=Abstract
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Sun protection behaviors and stages of change for the primary prevention of skin cancers among beachgoers in southeastern New England. Author(s): Weinstock MA, Rossi JS, Redding CA, Maddock JE, Cottrill SD.
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Source: Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine. 2000 Fall; 22(4): 286-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11253439&dopt=Abstract •
Tanning beds and skin cancer: artificial sun + old sol = real risk. Author(s): Spencer JM, Amonette R. Source: Clinics in Dermatology. 1998 July-August; 16(4): 487-501. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9699061&dopt=Abstract
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The state-of-the-art in chemoprevention of skin cancer. Author(s): Stratton SP, Dorr RT, Alberts DS. Source: European Journal of Cancer (Oxford, England : 1990). 2000 June; 36(10): 1292-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10882869&dopt=Abstract
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The use of positron emission tomography to develop boron neutron capture therapy treatment plans for metastatic malignant melanoma. Author(s): Kabalka GW, Nichols TL, Smith GT, Miller LF, Khan MK, Busse PM. Source: Journal of Neuro-Oncology. 2003 March-April; 62(1-2): 187-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749713&dopt=Abstract
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Use of alternative therapies by patients undergoing surgery for nonmelanoma skin cancer. Author(s): Dinehart SM, Alstadt K. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2002 June; 28(6): 443-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081668&dopt=Abstract
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Use of tanning devices and risk of basal cell and squamous cell skin cancers. Author(s): Karagas MR, Stannard VA, Mott LA, Slattery MJ, Spencer SK, Weinstock MA. Source: Journal of the National Cancer Institute. 2002 February 6; 94(3): 224-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11830612&dopt=Abstract
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Vitamins and carotenoids intake and the risk of basal cell carcinoma of the skin in women (United States). Author(s): Fung TT, Hunter DJ, Spiegelman D, Colditz GA, Speizer FE, Willett WC. Source: Cancer Causes & Control : Ccc. 2002 April; 13(3): 221-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020103&dopt=Abstract
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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.com: 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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WebMDHealth: 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 skin 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 Cancer Prevention (Reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com Cervical Dysplasia Source: Integrative Medicine Communications; www.drkoop.com Colon Cancer Source: Healthnotes, Inc. www.healthnotes.com Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Dermatitis Source: Integrative Medicine Communications; www.drkoop.com
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Frostbite Source: Integrative Medicine Communications; www.drkoop.com Lung Cancer Source: Healthnotes, Inc. www.healthnotes.com Pap Smear, Abnormal Source: Integrative Medicine Communications; www.drkoop.com Photodermatitis Source: Integrative Medicine Communications; www.drkoop.com Prostate Cancer Source: Healthnotes, Inc. www.healthnotes.com Prostate Cancer Source: Integrative Medicine Communications; www.drkoop.com Skin Cancer Source: Integrative Medicine Communications; www.drkoop.com Skin cancer Source: Integrative Medicine Communications; www.drkoop.com Skin Disorders, Dermatitis Source: Integrative Medicine Communications; www.drkoop.com Skin Disorders, Photodermatitis Source: Integrative Medicine Communications; www.drkoop.com Sunburn Source: Integrative Medicine Communications; www.drkoop.com Uveitis Source: Integrative Medicine Communications; www.drkoop.com Vitiligo Source: Healthnotes, Inc. www.healthnotes.com •
Herbs and Supplements ALA Source: Integrative Medicine Communications; www.drkoop.com Alpha-Linolenic Acid (ALA) Source: Integrative Medicine Communications; www.drkoop.com Betula Alternative names: Birch; Betula sp. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org
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Bloodroot Source: Prima Communications, Inc.www.personalhealthzone.com Brahmi Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Bryonia Bryony Alternative names: Bryony; Bryonia sp. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Calciferol Source: Integrative Medicine Communications; www.drkoop.com Calcitrol Source: Integrative Medicine Communications; www.drkoop.com Centella Source: Integrative Medicine Communications; www.drkoop.com Centella asiatica Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com CHAPARRAL Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Chemotherapy 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 Curcuma longa Source: Integrative Medicine Communications; www.drkoop.com Cyclophosphamide Source: Healthnotes, Inc. www.healthnotes.com Docetaxel Source: Healthnotes, Inc. www.healthnotes.com
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Erocalciferol Source: Integrative Medicine Communications; www.drkoop.com Flaxseed Alternative names: Linum usitatissimum, Linseed Source: Integrative Medicine Communications; www.drkoop.com Fluorouracil Source: Healthnotes, Inc. www.healthnotes.com Gamma-Linolenic Acid (GLA) Source: Integrative Medicine Communications; www.drkoop.com GLA Source: Integrative Medicine Communications; www.drkoop.com Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Gotu Kola Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Green Tea Alternative names: Camellia sinensis Source: Healthnotes, Inc. www.healthnotes.com Green tea Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10032,00.html Hydrocotyle Source: Integrative Medicine Communications; www.drkoop.com Indian Pennywort Source: Integrative Medicine Communications; www.drkoop.com Linseed Source: Integrative Medicine Communications; www.drkoop.com Linum usitatissimum Source: Integrative Medicine Communications; www.drkoop.com Luffa Alternative names: Luffa sp. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Lycopene
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Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,803,00.html Marsh Pennywort Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Melatonin Source: Healthnotes, Inc. www.healthnotes.com Methotrexate Source: Healthnotes, Inc. www.healthnotes.com Milk thistle Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10044,00.html Paclitaxel Source: Healthnotes, Inc. www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Phenylalanine Source: Integrative Medicine Communications; www.drkoop.com Phytolacca Alternative names: Poke root, Endod; Phytolacca dodecandra L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Silybum Alternative names: Milk Thistle; Silybum marianum (L.) Gaertn. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Tocotrienols Source: Healthnotes, Inc. www.healthnotes.com Turmeric Alternative names: Curcuma longa Source: Healthnotes, Inc. www.healthnotes.com Turmeric Alternative names: Curcuma longa Source: Integrative Medicine Communications; www.drkoop.com
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Tyrosine Source: Integrative Medicine Communications; www.drkoop.com Yucca Alternative names: Yucca schidigera , Yucca spp. Source: Healthnotes, Inc. www.healthnotes.com Zingiber Alternative names: Ginger; Zingiber officinale Roscoe Source: Alternative Medicine Foundation, Inc. www.amfoundation.org 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 SKIN CANCER Overview In this chapter, we will give you a bibliography on recent dissertations relating to skin 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 “skin cancer” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on skin cancer, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Skin 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 skin 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 Novel Automated Mueller Matrix Polarization Imaging System for Skin Cancer Detection by Chung, Jung Rae; Phd from Texas A&m University, 2003, 119 pages http://wwwlib.umi.com/dissertations/fullcit/3088128
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Arsenic Exposure, Artificial Tanning and Melanoma in Iowa by Beane Freeman, Laura Elizabeth; Phd from The University of Iowa, 2003, 214 pages http://wwwlib.umi.com/dissertations/fullcit/3087609
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College Students' Knowledge and Attitudes about Cancer and Perceived Risks of Developing Skin Cancer by Lamanna, Lenore Mary; Edd from Columbia University Teachers College, 2003, 200 pages http://wwwlib.umi.com/dissertations/fullcit/3080059
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Continuity of Care As a Predictor of Melanoma Thickness: Analysis of Nove Scotia Population-based Secondary Data Resources by Di Quinzio, Melanie L. Msc from Dalhousie University (canada), 2002, 85 pages http://wwwlib.umi.com/dissertations/fullcit/MQ75461
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Coverage of Skin Cancer Prevention in Professional Journals and the Popular Press by Miner, Kimberly Jean, Phd from Texas Woman's University, 1992, 115 pages http://wwwlib.umi.com/dissertations/fullcit/9300181
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Preventing Environmentally Induced Skin Cancer Through Risk Communication and Organizational Change (cancer Prevention) by Seiver, Owen H., Dpa from University of La Verne, 1991, 191 pages http://wwwlib.umi.com/dissertations/fullcit/9128130
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Skin Cancer Diagnosis Using Hybrid Artificial Intelligence System by Chang, Ying; Phd from University of Missouri - Rolla, 2002, 131 pages http://wwwlib.umi.com/dissertations/fullcit/3053621
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Skin Cancer Information and Intentions to Perform Skin Cancer Prevention Behaviors by Schulz, Jeffrey Wayne, Phd from University of Arkansas, 1997, 151 pages http://wwwlib.umi.com/dissertations/fullcit/9820810
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Skin Cancer Prevention among Health Care Providers during Routine Office Visits in Los Angeles, California by Kim, Jemy Francisco; Ms from California State University, Long Beach, 2002, 70 pages http://wwwlib.umi.com/dissertations/fullcit/1409208
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 SKIN CANCER Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning skin cancer.
Recent Trials on Skin Cancer The following is a list of recent trials dedicated to skin cancer.8 Further information on a trial is available at the Web site indicated. •
A Phase II Study of Isolated Hepatic Perfusion (IHP) in Patients with Ocular Melanoma Condition(s): Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: Ocular melanoma, or cancer of the eye, is a rare form of cancer that can spread to the liver. A tumor in the liver, because of its size or location, sometimes cannot be removed with surgery. The purpose of this study is to determine whether chemotherapy delivered only to the liver, called isolated hepatic perfusion (IHP), followed by systemic (to the whole body) chemotherapy improves the ability to treat cancer. Study participants must be 18 years or older and have ocular melanoma that has spread to the liver. Before enrolling in the study, they will undergo the following evaluations: a physical exam; x-rays; blood tests; electrocardiogram; computed tomography (CT) scan of the chest, abdomen and pelvis; and a magnetic resonance imaging (MRI) scan of the liver. The study includes a 15-minute quality-of-life questionnaire. Participants will complete the questionnaire 7 times over a period of 2 years to help investigators gauge their health status and progress. A laparotomy is done, which allows a surgeon to view the tumor in the liver through a small incision in the abdomen while the patient is under general anesthesia. Sometimes the tumor can spread outside the liver in a way that cannot be seen by pre-operative scans. When this happens, the participant is ineligible to continue in the study, since an important part of
8
These are listed at www.ClinicalTrials.gov.
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the treatment is given only to the liver. If the laparotomy reveals that the participant is eligible for the remainder of the study, the participant will receive IHP treatment during the surgery. Plastic tubes called catheters are placed in the vein and artery that feed and drain the liver. This creates a separate blood supply for the liver alone. Heated chemotherapy is then given into the liver blood supply for one hour, while being carefully kept out of the rest of the body. After recovering from the surgery, eligible participants will receive a systemic chemotherapy called temozolomide for up to one year. This chemotherapy is taken by mouth in capsule form. Participants will be asked to return to NIH 10-11 times during the first year to evaluate their progress. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00062933 •
Aldara(tm) (Trademark) (Imiquimod) Cream to Treat Basal Cell Carcinoma Condition(s): Basal Cell Carcinoma Study Status: This study is currently recruiting patients. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: This study will evaluate the effectiveness of Aldara(tm) (Trademark) (Imiquimod) Cream in treating basal cell carcinoma (skin cancer). Patients 18 years of age and older with an untreated suspected basal cell carcinoma may be eligible for this study. First Visit: Participants will have a medical history taken. A blood sample will be drawn and a doctor will examine, measure, and photograph the skin lesion. Two punch skin biopsies (surgical removal of a small piece of tissue for microscopic examination), will be taken from the area of the skin cancer, each less than 1/8th inch in diameter. One sample will be examined to confirm the diagnosis of basal cell carcinoma; the other will be sent to a laboratory for special tests that will be compared with another skin sample taken after treatment. In addition, a small amount of tissue will be removed from the area of skin cancer with a very fine needle. Patients will be shown how to apply the study cream and will be given a dosing kit with a supply of cream to take home. The cream contains either Aldara cream or a placebo (look-alike cream with no active ingredient). Treatment Initiation Patients will be randomly assigned to one of four treatment dosing groups. They will apply the cream as instructed in their kit according to one of the following schedules: - Four doses, one dose every 12 hours, twice a day Four doses, one dose every 24 hours, once a day - Eight doses, one dose every 12 hours, twice a day - Eight doses, one dose every 24 hours, once a day End-of-Treatment Visit Patients will come to the clinic about 24 hours after their last dose for an end-oftreatment visit. A doctor will examine and photograph the skin cancer area. A second punch biopsy and fine needle aspiration will be taken and sent for special tests at a research laboratory. The doctor will then surgically remove the entire skin cancer and send it to a laboratory to be examined for skin cancer cells. Upon starting treatment and at each clinic visit, participants will report any illnesses, side effects, or reactions to the study drug and will be asked about any medications they have taken. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00045851
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Clinical, Laboratory, and Epidemiologic Characterization of Individuals and Families at High Risk of Melanoma Condition(s): Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will investigate how genetic and environmental factors contribute to the development of melanoma, a type of skin cancer, and related conditions. Individuals of any age with a personal or family history of melanoma may be eligible for this study. Participants will: - Fill out one or two questionnaires about their personal and family medical history. - Provide written consent for researchers to review their medical records and pathology materials related to their care and those of deceased relatives with melanomas, tumors, cancer, or other related illnesses for whom they are the next-of-kin or legally authorized representative. - Donate a blood or cheek cell sample to be used for genetic studies. (The blood sample is collected through a needle in an arm vein. The cheek cell sample is obtained either by gently brushing the inside of the mouth with a soft brush or by swishing a tablespoon of mouthwash and then spitting it into a container.) - Undergo a skin biopsy (removal of a small piece of skin tissue) for genetic study. For this procedure, the area of skin to be removed is numbed with a local anesthetic and a 1/4-inch piece of skin is excised with a cookie cutter-like instrument. The wound is then covered with a band-aid. Participants may be asked to travel to the NIH Clinical Center for evaluation, including a medical history, physical examination, and some of the following procedures: - Full body skin examination to evaluate the type and number of moles and document any evidence of sun damage to the skin. The examination involves all the skin from the scalp to the bottoms of the feet. After the examination, a medical photographer will photograph the skin, with close-ups of skin lesions marked by the examiner. If there are parts of the skin the participant does not want examined or photographed, he or she can tell the examiner. - Blood draw of about 120 milliliters (4 ounces) or less - Skin biopsy - Cheek cell sample - X-rays, ultrasound and magnetic resonance imaging (MRI) studies to detect tumors or changes in tumors or other types of changes in specific tissues. MRI is a diagnostic test that uses strong magnetic fields and radiowaves to examine body tissues. The subject lies on a table that is moved into a large tunnel-like machine (the scanner) for about 45 minutes to 1 hour. When the tests are finished, a doctor will discuss the results with the participant and the need, if any, for clinical follow-up. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00040352
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CTLA-4 Antibody (MDX-010) Plus Interleukin-2 to Treat Advanced Melanoma Condition(s): Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will determine the highest dose of MDX-010 that can safely be given in conjunction with interleukin2 (IL-2) to patients with advanced melanoma, and to examine its effectiveness against the cancer. MDX-010 is designed to increase immunity to cancer. It is a laboratory-produced antibody to the CTLA-4 protein found on certain lymphocytes (a type of white blood cell). When lymphocytes recognize a foreign substance, such as a virus or bacteria, they initiate an immune response to fight
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and control the infection. Once this is achieved, CTLA-4 proteins help stop the immune response, decreasing the number of immune cells against the virus or bacteria. When an immune response is mounted against tumor cells, however, it may be beneficial not to stop the immune response, but instead, to keep a large number of lymphocytes available to recognize and fight tumor cells. In this study, MDX-010 will be used to block CTLA-4 and maintain immune activity. IL-2 is a naturally occurring substance whose main function is to signal immune cells to become active. FDA has approved IL-2 for treating patients with advanced melanoma and kidney cancer. Patients 16 years of age and older with stage IV melanoma (melanoma that has spread to the lymph nodes or other sites) and whose tumor is not responding to standard treatments may be eligible for this study. Each candidate will be screened with a history, physical examination, blood test, and electrocardiogram (EKG). X-rays and scans will be done to evaluate the size and extent of their tumor, if current ones are not available. Participants will receive up to four MDX-010 treatments 21 days apart. Each treatment consists of a dose of MDX-010 given intravenously (through a vein) via a catheter (thin plastic tube) over 90 minutes. IL-2 will also be given after the second and third injection of MDX-010 through a small catheter over a 15-minute period every 8 hours for as many doses as are tolerated. In addition to treatment, patients will have the following tests and procedures: - Blood tests before and during the first injection of MDX-010 and blood tests before, during and for 6 days after the second injections of MDX-010 to measure levels of the antibody, and then blood tests every 21 days (every treatment visit) to examine the body's reaction to the treatment. -Leukapheresis to study the effects of treatment on the immune system. For this procedure, blood is drawn through a needle in an arm vein and circulated through a machine that separates the blood into its components (red cells, white cells, platelets, and plasma). The lymphocytes are extracted and the rest of the blood is returned to the patient through a needle in the other arm. Leukapheresis is done just before beginning treatment and may be repeated about three weeks after the fourth treatment. - Biopsy of normal skin and tumor or lymph node to examine the effects of antibody on the immune cells in the tumor. For this procedure, a needle is put into the skin or tumor and a small amount of tissue is pulled out with the needle. Biopsies are optional; they are not required for participation in the study. - Follow-up visit 3 weeks after the fourth treatment for a checkup examination, scans and X-rays, and blood tests. Patients will be watched closely for treatment side effects. Those who develop severe drug side effects, whose bodies develop an immune reaction against the MDX-010 antibody, or whose conditions worsen during treatment may be withdrawn from the study. Those whose tumors have stabilized or shrunk will continue follow-up visits. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055211 •
gp100 and MDX-CTLA4 Vaccination for Stage IV Melanoma Condition(s): Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will examine the safety and effectiveness of an experimental vaccine given with an immune booster to treat advanced melanoma. The vaccine contains peptides (pieces of proteins) of two gp100 proteins, which are
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produced by melanoma tumors. The vaccine injections are mixed with an oil-based substance called Montanide ISA-51, which is intended to increase the immune response to the peptides. The vaccine will be given along with CTLA-4 antibody, an immune booster. Patients 16 years of age and older with melanoma that has spread from the primary site and does not respond to standard treatment may be eligible for this study. Candidates will be screened with a physical examination, eye examination, blood tests, electrocardiogram, and imaging studies (x-rays and scans) to check the size and extent of tumor, and lung function tests, if medically indicated. Because the vaccine formulation is based on tissue type, only patients with tissue type HLA-A*0201 may participate. Tissue type is determined by a blood test. Participants will receive CTLA-4 antibody, administered intravenously (IV) over 90 minutes through a catheter (plastic tube) placed in a vein. They will then be given four injections of the peptide vaccines in the thigh. The vaccination plus antibody treatments will be given four times-once every 3 weeks. Participants will have blood tests and physical examinations at each clinic visit to measure CTLA-4 antibody levels and look for changes in the blood that signal reactions to the vaccine or antibody, and to check for side effects. During the first injection of CTLA-4 antibody and for 6 hours after, six small blood samples will be taken to measure levels of the antibody. Once a day for 3 days after the first vaccine injection, and once a week for the next 3 weeks, a nurse will call the patient at home to check health status and drug side effects. Patients will also undergo plasmapheresis-a procedure to collect quantities of white blood cells-before treatment begins and possibly again 3 weeks after the second and fourth vaccinations. For this procedure, blood is drawn through a needle in the arm and circulated through a machine that spins it to separate the components. The white cells are removed and the plasma and red cells are returned to the patient through a needle in the other arm. Some patients may also have a biopsy of normal skin and tumor or lymph node tissue to examine the effects of the vaccine on the tumor immune cells. This involves drawing a small amount of tissue through a needle put in the skin. Patients will return to the clinic 3 weeks after the fourth vaccination for a follow-up examination and blood tests. Patients who experience severe side effects to the vaccine or develop an immune reaction against CTLA-4 antibody, or whose condition worsens with treatment, may be taken off the study. Patients whose disease has not progressed or whose tumor has shrunk may receive another course of four vaccinations, with continued follow-up if the disease improves. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029549 •
Hyperthermic Isolated Limb Perfusion and Melphalan with or without Tumor Necrosis Factor to Treat Advanced Melanoma in a Limb Condition(s): Malignant Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study, conducted by the American College of Surgeons Oncology Group, will examine the safety and effectiveness of adding tumor necrosis factor (TNF) to a regimen of hyperthermic isolated limb perfusion (ILP) plus chemotherapy for treating melanoma in an arm or leg. With ILP, chemotherapy is given in high concentrations directly into the main blood vessels supplying the affected limb. The drugs circulate through the blood vessels for a short time and are then flushed out
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of the body. Before giving the drugs, the blood in the limb is heated in a process called hyperthermia to enhance the drugs' effectiveness. The anti-cancer drug melphalan is used in standard hyperthermic ILP treatment. This study will see if adding TNF to the treatment regimen can enhance tumor shrinkage and prolong disease remission. It will also compare the side effects and long-term effects of the two treatments. Patients 18 years of age or older with advanced melanoma in an arm or leg may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood and urine tests, chest x-ray, electrocardiogram, tumor biopsy, Computed Tomography (CT) imaging scans of the chest, abdomen, pelvis and brain, and a magnetic resonance imaging (MRI) scan of the brain. Whole body scans will be done, if needed. These tests will be done within 90 days of starting treatment. Participants will be randomly assigned to one of two treatment groups. Group 1 will receive ILP with hyperthermia using melphalan. Group 2 will receive ILP with hyperthermia using melphalan and TNF. All participants will receive hyperthermia under general anesthesia in the operating room. Tubes will be inserted into a vein in the neck or under the collarbone and then into blood vessels leading to the affected limb. A machine like the one used in open-heart surgery will circulate the blood and the drugs through these tubes during the procedure. A tourniquet will be placed on the limb to keep the drugs from entering the blood supply to the rest of the body. The blood from the limb will be heated to 102(Infinite) F to 105(Infinite) F (about the temperature of a hot tub) while it circulates through the machine. A radioactive chemical will be put in the blood to see how much of the drugs get into the blood supply and if any drug leaks to the rest of the body. In patients with melanoma in the leg, the lymph nodes in the groin will be removed if the cancer has spread to those nodes. In patients with melanoma in an arm, lymph nodes in the armpit will be removed whether or not they appear to contain cancer cells. Patients' heart and blood pressure will be monitored closely for 1 to 2 days, and total hospitalization time will be 4 to 8 days. In addition to treatment, patients will undergo the following tests before ILP and at various intervals after the procedure: Measurements, photographs and biopsies of tumor deposits in the affected limb; Ultrasound, CT scan or MRI of the affected limb for measurement of deep-lying tumors; - Referral to cardiologist for examination and tests, as needed, in patients 40 years old or older; - Pregnancy test for women of child-bearing potential. If needed, patients will have ultrasound of the limb within a few days after treatment to look for blood clots. Patients receiving TNF will have blood samples collected from the affected limb before and after TNF is given to measure TNF blood levels. Patients will be followed for the rest of their life to determine long-term effects of the study procedures. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056732 •
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
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cancer, colon cancer, or melanoma. PURPOSE: Phase III trial to study the effectiveness 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 •
Interferon alfa Following Surgery in Treating Patients With Stage III Melanoma Condition(s): stage III melanoma Study Status: This study is currently recruiting patients. Sponsor(s): EORTC Melanoma Cooperative Group Purpose - Excerpt: RATIONALE: Interferon alfa may interfere with the growth of the cancer cells. It is not yet known if this treatment is more effective than observation following surgery for stage III melanoma. PURPOSE: Randomized phase III trial to determine the effectiveness of interferon alfa in treating patients who have undergone surgery for stage III melanoma. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006249
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Isolated Limb Infusion of Chemotherapy in Treating Patients With Melanoma or Soft Tissue Sarcoma of the Arm or Leg That Cannot Be Removed By Surgery Condition(s): adult soft tissue sarcoma; Melanoma; recurrent adult soft tissue sarcoma; Recurrent Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; 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. Infusing chemotherapy to the tumor area only may kill more tumor cells and cause less damage to healthy tissues. PURPOSE: Phase II trial to study the effectiveness of isolated limb infusion of chemotherapy in treating patients who have melanoma or soft tissue sarcoma of the arm or leg 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/NCT00004250
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Monoclonal Antibody Therapy in Treating Patients With Ovarian Epithelial Cancer, Melanoma, Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Non-Small Cell Lung Cancer Condition(s): Acute Myeloid Leukemia; Melanoma; Non-small cell lung cancer; Recurrent Melanoma; recurrent ovarian epithelial cancer Study Status: This study is currently recruiting patients. Sponsor(s): Dana-Farber/Harvard Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy in treating patients who have ovarian epithelial cancer, melanoma, acute myeloid leukemia, myelodysplastic syndrome, or non-small cell lung cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00039091
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Novel Adjuvants for Peptide-Based Melanoma Vaccines Condition(s): Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): FDA Office of Orphan Products Development Purpose - Excerpt: This is a study to determine the efficacy of a melanoma vaccine chemotherapy cocktail composed of CTLA-4 antibody; tyrosinase, gp100, and MART-1 peptides; and incomplete Freund's adjuvant (IFA) with or without interleukin-12 in patients with resected stage III or IV melanoma. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00028431
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Peptide Vaccination for Patients at High Risk for Recurrent Melanoma Condition(s): Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will examine the effectiveness and side effects of an experimental vaccine to prevent recurrence of melanoma. The likelihood of melanoma returning is higher in patients who have melanoma lesions deep in the skin, in patients who have had positive lymph nodes, and in patients who have had surgery for metastatic disease (cancer that has spread beyond the primary site). melanoma tumors produce proteins called gp100 and MART-1. Vaccination with specific pieces of these proteins (peptides) may boost the immune system's fight against the cancer. The vaccine injections are mixed with an oil-based substance called Montanide ISA-51, which is intended to increase the immune response to the peptide. Patients 16 years of age and older whose melanoma has been surgically removed and who are currently free of
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disease may be eligible for this study. Candidates will be screened with a physical examination and blood and urine tests. An electrocardiogram (EKG), x-rays and other imaging studies will be done if recent results are not available. Some candidates may require heart tests, such as a cardiac stress test or echocardiogram, or lung function tests. In addition, all candidates will be tested for HLA tissue type; patients must be type HLA-A*0201, the type on which this vaccine is based. Participants will be randomly assigned to receive one of four different vaccines to determine which peptides offer the best immunity. Each treatment course consists of two injections of the vaccines every 3 weeks for four times. The injections are given under the skin of the thigh. After every other treatment course (every 6 months), patients will undergo a series of x-rays and scans to look for tumor. The immunizations may continue for up to 12 months as long as the melanoma does not return. The injections are given at the NIH Clinical Center. Patients are monitored for 1 hour after each injection and have blood tests and a physical examination to look for treatment side effects. Patients will be followed with blood tests every 12 weeks to monitor body functions. They will also undergo leukapheresis-a procedure to collect white blood cells-before starting treatment and about 3 to 4 weeks after the fourth vaccine to evaluate how the vaccines affect the action of the immune system cells. For this procedure, blood is drawn through a needle in the arm, similar to donating blood. The blood goes through a machine that separates out the lymphocytes (white blood cells), and the rest of the blood is returned through a needle in the other arm. Some patients may undergo a biopsy-surgical removal of a small piece of tissue under local anesthetic-of normal skin and tumor or lymph node tissue to examine the effects of the vaccines on the tumor immune cells. Patients whose disease returns during the first course of vaccine therapy will have surgery to remove the tumor and will continue to receive the vaccine treatment. Patients whose tumor returns after completing one course of therapy may receive a substance called interleukin-2 (IL-2), which can boost immune function against the tumor. IL-2 is given intravenously (through a small tube placed in a vein) every 8 hours for 4 days. This regimen is repeated after 10 to 14 days. Those who respond to IL-2 will have a third course of treatment after 2 months. Patients whose disease recurs after treatment will be taken off the study and will be referred back to their referring physician or to another study, if an appropriate one is available. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00059475 •
Peripheral Stem Cell Transplantation Plus Monoclonal Antibody Therapy in Treating Patients With High-Risk Hematologic Cancer, Refractory Breast or Kidney Cancer, or Melanoma Condition(s): Breast Cancer; chronic myeloproliferative disorders; kidney tumor; Leukemia; Melanoma; plasma cell neoplasm Study Status: This study is currently recruiting patients. Sponsor(s): Duke Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Peripheral stem cell transplantation replaces immune cells that were destroyed by chemotherapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Treatment of the cells with a monoclonal antibody may prevent this from happening. PURPOSE: Phase II trial to study the effectiveness of peripheral stem cell transplantation
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plus monoclonal antibody therapy in treating patients who have high-risk hematologic cancer, refractory breast or kidney cancer, or melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004143 •
Phase I Study of gp75 Vaccine in Patients with Stage III and IV Melanoma Condition(s): Malignant Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): ImClone Systems; Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: Up to 24 patients with stage III or stage IV melanoma will be enrolled. Patients who are currently disease-free but at high risk for relapse are also eligible. Patients will receive vaccinations of gp75 at assigned dose levels. Patients who exhibit serologic and stable/clinical response are eligible to receive booster vaccinations. Patients will be evaluated for safety and efficacy throughout the duration of the study. In this study, the optimal biologically effective dose is defined as the lowest dose of gp75 that results in the production of anti-gp75 antibodies. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00034554
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Phase II Trial of Allovectin-7(r) for Metastatic Melanoma Condition(s): Melanoma; Metastatic Melanoma; Malignant Melanoma; Skin Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Vical Purpose - Excerpt: The purpose of this clinical trial is to determine if Allovectin-7(r), an experimental gene-based immunotherapy, can shrink melanoma tumors. The trial will also examine if this treatment can improve the time to disease progression. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044356
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Photodynamic Therapy in Treating Patients With Basal Cell Skin Cancer Condition(s): basal cell carcinoma of the skin; recurrent skin cancer Study Status: This study is currently recruiting patients. Sponsor(s): Roswell Park Cancer Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Photodynamic therapy uses light and drugs that make cancer cells more sensitive to light to kill tumor cells. Photosensitizing drugs such as HPPH are absorbed by cancer cells and, when exposed to light, become active and kill
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the cancer cells. PURPOSE: Phase I trial to study the effectiveness of photodynamic therapy with HPPH in treating patients who have basal cell skin cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00017485 •
Study of Heat Shock Protein-Peptide Complex (HSPPC-96) versus IL-2/DTIC for Stage IV Melanoma Condition(s): Malignant Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): Antigenics Purpose - Excerpt: The primary goal of this study is to determine if people with metastatic melanoma who receive Heat Shock Protein-Peptide Complex - 96 (HSPPC-96 or Oncophage) after surgery live longer than people who may or may not have surgery but who receive conventional chemotherapy including IL-2/DTIC. A second goal is to determine the safety and frequency of side effects in subjects who receive therapy with HSPPC-96. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00039000
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Study of ILX651 in Patients with Recurrent or Metastatic Melanoma Condition(s): Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): ILEX Products Purpose - Excerpt: This is a Phase II, non-randomized, open label study of ILX651 in patients with recurrent or metastatic melanoma after prior biological therapy. Approximately 60 patients will be enrolled in this study that is expected to last 18 months. All patients will be treated with ILX651 administered IV daily for 5 consecutive days once every 21 days. The primary objective of this study is to determine the overall response rate for recurrent or metastatic melanoma patients who are treated with ILX651. The secondary objectives are to determine the progression free survival at 18 weeks, duration of response, time to tumor progression, survival, safety/tolerability of ILX651 and to evaluate the pharmacokinetic profile. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00068211
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Two studies to determine if verteporfin PDT is effective & safe in treating multiple basal cell carcinoma of the skin. Condition(s): Basal Cell Carcinoma; Nevoid Basal Cell Carcinoma Syndrome; Gorlin Syndrome Study Status: This study is currently recruiting patients. Sponsor(s): QLT Inc; Novartis Pharmaceuticals Purpose - Excerpt: The purpose of the two studies is to determine whether an experimental therapy using a photoactive drug, verteporfin, in combination with direct light exposure of basal cell carcinoma of the skin can safely eliminate these skin tumors. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049959
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Tyrosinase-Related Protein (TRP-2) Vaccination for Metastatic Melanoma Condition(s): Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will test the safety and effectiveness of an experimental vaccine for fighting metastatic melanoma. The vaccine contains a peptide (piece of a protein) called tyrosinase-related protein-2 (TRP-2), which is made by some kinds of cancers. It also contains an oil-based liquid called Montanide ISA-51, another experimental substance, which is intended to boost the immune reaction to the peptide. Patients 16 years of age and older who have metastatic melanoma that does not respond to standard treatment may be eligible for this study. Candidates will be screened with a medical history and physical examination, chest X-ray, electrocardiogram, blood and urine tests, and X-rays and scans to the evaluate the extent and size of the tumor. Because the vaccine formulation is based on tissue type, only patients with tissue type HLA-A*0201 may participate. Tissue type is determined by a blood test. Depending on the size and extent of tumor, participants will receive either the vaccine alone or the vaccine plus interleukin-2 (IL-2), a drug that boosts the immune reaction to the tumor. Patients who do not immediately require IL-2 will be randomly assigned to receive the vaccine either 1) once a week for 4 weeks, followed by a 3-week break, and then again once a week for 4 weeks; or 2) once every 3 weeks for four times. The vaccine is given as an injection (shot) in the thigh. A physical examination and blood tests will be done at each treatment visit to monitor side effects and any reaction to the vaccine. For patients receiving IL-2, this drug will be infused through a vein over 15 minutes every 8 hours for 4 days after each vaccine injection. They will be required to stay in the hospital for about one week during each treatment cycle. About 40 cc (8 teaspoons) of blood will be drawn every 3 weeks to monitor body functions. Patients will undergo leukapheresis to evaluate how the vaccine affects the action of lymphocytes-white blood cells of the immune system. For this procedure, whole blood is collected through a needle placed in an arm vein. The blood circulates through a machine that separates it into its components. The lymphocytes are then removed and the rest of the blood-red cells, platelets and plasma-is returned to the body through a second needle in the other arm. All patients will undergo leukapheresis just before beginning treatment. The procedure may be repeated after the fourth and eighth vaccines in patients receiving weekly
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injections, and after the second and fourth vaccine cycles in patients receiving injections every 3 weeks. Patients will return for follow-up studies after the fourth and eighth weekly injections, or after the second and fourth injections for those on the every-3weeks injection schedule. If the tumor has responded to the vaccine, the treatment may be repeated on the same schedule for up to 12 months, with continuing follow-up visits. Some patients may have a needle biopsy of normal skin and tumor or lymph node to examine the effects of the vaccine on the immune cells in the tumor. For this procedure, a needle is put into the skin or tumor and a small amount of tissue is withdrawn. Patients whose cancer progresses during treatment with the peptide vaccine alone may then receive IL-2 if their condition permits. In other studies with melanoma patients, those who received a peptide vaccine plus IL-2 had more tumor shrinkage than those receiving just vaccine alone or just IL-2 alone. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00017849 •
Vaccine Therapy and Interleukin-12 With Either Alum or Sargramostim After Surgery in Treating Patients With Melanoma Condition(s): intraocular melanoma; Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): University of Southern California; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Vaccines made from peptides may make the body build an immune response. Combining vaccine therapy with interleukin-12 and either alum or sargramostim may kill more tumor cells. PURPOSE: Randomized phase II trial to compare the effectiveness of combining vaccine therapy with interleukin-12 and either alum or sargramostim in treating patients who have undergone surgery for stage II, stage III, or stage IV melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00031733
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Vaccine Therapy and/or Sargramostim in Treating Patients With Locally Advanced or Metastatic Melanoma Condition(s): intraocular melanoma; Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): Eastern Cooperative Oncology Group; National Cancer Institute (NCI); Southwest Oncology Group Purpose - Excerpt: RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim increase the number of immune cells found in bone marrow or peripheral blood. It is not yet known which treatment regimen is more effective for metastatic melanoma. PURPOSE: Randomized phase III trial to determine the effectiveness of peptide vaccine therapy
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and/or sargramostim in treating patients who have locally advanced or metastatic melanoma. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005034 •
Vaccine Therapy Followed by Biological Therapy in Treating Patients With Stage III or Stage IV Melanoma Condition(s): stage III melanoma; Stage IV Melanoma; Recurrent Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): University of Southern California; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Vaccines made from melanoma cells may make the body build an immune response to kill tumor cells. Biological therapies such as interferon gamma and interleukin-2 use different ways to stimulate the immune system and stop cancer cells from growing. Combining vaccine therapy with biological therapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of vaccine therapy, interferon gamma, and interleukin-2 in treating patients who have stage III or stage IV melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006113
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Vaccine Therapy in Treating Patients With Primary Stage II Melanoma Condition(s): stage II melanoma Study Status: This study is currently recruiting patients. Sponsor(s): EORTC Melanoma Cooperative Group Purpose - Excerpt: RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. It is not yet known whether vaccine therapy is more effective than observation alone for melanoma. PURPOSE: Randomized phase III trial to determine the effectiveness of vaccine therapy in treating patients who have primary stage II melanoma. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005052
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Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma Condition(s): stage III melanoma; Stage IV Melanoma; Recurrent Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen
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Purpose - Excerpt: RATIONALE: Vaccines made from a person's white blood cells mixed with tumor proteins may make the body build an immune response to kill tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have stage III or stage IV melanoma. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053391 •
Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma Condition(s): Recurrent Melanoma; stage III melanoma; Stage IV Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen Purpose - Excerpt: RATIONALE: Vaccines made from a person's white blood cells mixed with tumor proteins may make the body build an immune response to kill tumor cells. Biological therapies such as denileukin diftitox may be able to deliver cancerkilling substances directly to melanoma cells. Combining vaccine therapy with biological therapy may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combining vaccine therapy with denileukin diftitox in treating patients who have stage III or stage IV melanoma. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056134
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Vaccine Therapy With High-Dose Interleukin-2 in Treating Patients With Metastatic Melanoma Condition(s): Stage IV Melanoma; Recurrent Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): University of Illinois; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Vaccines may make the body build an immune response that will kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. PURPOSE: Randomized phase II trial to study the effectiveness of vaccine therapy with interleukin-2 in treating patients with metastatic melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003568
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Vaccine Therapy With or Without Sargramostim in Treating Patients With High-Risk or Metastatic Melanoma Condition(s): stage III melanoma; Stage IV Melanoma; Recurrent Melanoma
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Study Status: This study is currently recruiting patients. Sponsor(s): Herbert Irving Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood. Combining vaccine therapy with sargramostim may kill more tumor cells. PURPOSE: Randomized phase I trial to study the effectiveness of vaccine therapy with or without sargramostim in treating patients who have metastatic melanoma. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00037037 •
Combination Chemotherapy in Treating Patients With Stage III or Stage IV Melanoma Condition(s): stage III melanoma; Stage IV Melanoma; Recurrent Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center 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 I/II trial to study the effectiveness of combination chemotherapy consisting of acetaminophen plus carmustine in treating patients who have stage III or stage IV melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003346
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Combination Chemotherapy, Interferon alfa, and Interleukin-2 in Treating Patients With Metastatic Melanoma Condition(s): Stage IV Melanoma; Recurrent Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC Melanoma Cooperative Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interferon alfa may interfere with the growth of the cancer cells. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. It is not yet known which treatment regimen is more effective in treating melanoma. PURPOSE: Randomized phase II trial to compare the effectiveness of two regimens of combination chemotherapy plus interferon alfa and interleukin-2 in treating patients who have metastatic melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below
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Web Site: http://clinicaltrials.gov/ct/show/NCT00002669 •
Flavopiridol in Treating Patients With Metastatic Malignant Melanoma Condition(s): Stage IV Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute of Canada 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 flavopiridol in treating patients who have metastatic malignant melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005971
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Interferon alfa and Thalidomide in Treating Patients With Stage IV Melanoma Condition(s): Stage IV Melanoma; Recurrent Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Southwest Oncology Group Purpose - Excerpt: RATIONALE: Interferon alfa may interfere with the growth of cancer cells and slow the growth of the tumor. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Combining interferon alfa with thalidomide may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of interferon alfa and thalidomide in treating patients who have stage IV melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00026520
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Melanoma Vaccine With or Without Sargramostim in Treating Patients With Stage IV Malignant Melanoma Condition(s): Stage IV Melanoma; Recurrent Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Mayo Clinic Cancer Center Purpose - Excerpt: RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood. PURPOSE: Randomized phase I trial to compare the effectiveness of melanoma vaccine with or without sargramostim in treating patients who have stage IV malignant melanoma. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below
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Web Site: http://clinicaltrials.gov/ct/show/NCT00006243 •
Temozolomide and Thalidomide in Treating Patients With Stage III or Stage IV Melanoma Condition(s): intraocular melanoma; Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; 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. Thalidomide may stop the growth of melanoma by stopping blood flow to the tumor. Combining chemotherapy with thalidomide may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness temozolomide plus thalidomide in treating patients who have stage III or stage IV melanoma that cannot be removed during surgery. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005815
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Temozolomide With or Without Radiation Therapy to the Brain in Treating Patients With Stage IV Melanoma That Is Metastatic to the Brain Condition(s): Stage IV Melanoma; Recurrent Melanoma; brain metastases Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC Melanoma Cooperative Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known if chemotherapy is more effective with or without radiation therapy in treating brain metastases. PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy with or without radiation therapy to the brain in treating patients who have stage IV melanoma with asymptomatic brain metastases. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00020839
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Thalidomide and SU5416 in Treating Patients With Metastatic Melanoma Condition(s): Stage IV Melanoma; Recurrent Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); University of Texas Purpose - Excerpt: RATIONALE: Thalidomide combined with SU5416 may stop the growth of metastatic melanoma by stopping blood flow to the tumor. PURPOSE: Phase II trial to study the effectiveness of combining thalidomide and SU5416 in treating patients who have metastatic melanoma.
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Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00017316 •
Vaccine Therapy in Treating Patients With Melanoma of the Eye Condition(s): ciliary body and choroid melanoma, medium/large size Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC Melanoma Cooperative Group; EORTC Ophthalmic Oncology Task Force Purpose - Excerpt: RATIONALE: Vaccines may make the body build an immune response to kill tumor cells and decrease the recurrence of melanoma of the eye. PURPOSE: Randomized phase III trial to determine the effectiveness of vaccine therapy in treating patients who are at high risk for recurrent melanoma of the eye. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00036816
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Biological Therapy in Treating Patients With Metastatic Melanoma Condition(s): Stage IV Melanoma; Recurrent Melanoma Study Status: This study is suspended. Sponsor(s): National Cancer Institute (NCI); Fred Hutchinson Cancer Research Center Purpose - Excerpt: RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. PURPOSE: Phase I/II trial to study the effectiveness of biological therapy in treating patients who have metastatic melanoma. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002786
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Biological Therapy in Treating Patients With Metastatic Melanoma Condition(s): Stage IV Melanoma; Recurrent Melanoma Study Status: This study is suspended. Sponsor(s): National Cancer Institute (NCI); Fred Hutchinson Cancer Research Center Purpose - Excerpt: RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Treating a person's white blood cells in the laboratory and then reinfusing them may cause a stronger immune response and kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of biological therapy in treating patients who have metastatic melanoma. Phase(s): Phase I
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00045149 •
Biological Therapy in Treating Patients With Metastatic Melanoma Condition(s): Stage IV Melanoma; Recurrent Melanoma Study Status: This study is suspended. Sponsor(s): National Cancer Institute (NCI); Fred Hutchinson Cancer Research Center Purpose - Excerpt: RATIONALE: Biological therapies use different ways to stimulate the immune system and stop tumor cells from growing. Treating a person's white blood cells in the laboratory and reinfusing them may cause a stronger immune response and kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of biological therapy in treating patients who have metastatic melanoma. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00045357
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Comparison of Two Kinds of Dendritic Cell Immunizations in Treating Melanoma Condition(s): Melanoma; Neoplasm Metastasis Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will look at the safety and effectiveness of immunizations derived from two different substances in fighting melanoma. Both immunizations will contain dendritic cells-a type of cell that boosts immune system activity-but the cells will be produced by two different methods and their effects on the immune response compared. The body normally produces small amounts of dendritic cells, but large numbers of these cells can be made in the laboratory. In this study, one group of patients will receive dendritic cells derived from a type of white blood cell called monocytes, and a second group will receive cells derived from what are called stem cells. Small amounts of protein substances called gp100 and MART-1 that are found in most melanoma cells will be added to both types of dendritic cells. These protein substances may provoke the immune system to attack the tumor cells in much the same way a vaccine works. Patients in both groups will receive four cycles of immunizations four weeks apart. In the first two cycles, the cells will be injected into lymph vessels, and in the next two, they will be injected under the skin. Patients will also undergo apheresis-a procedure in which whole blood is drawn much like donating blood, but the lymphocytes are separated out by a machine and the rest of the blood is then returned to the body. This procedure may be repeated from two to four times during the study, depending on which immunization group the patient is in. Some patients may be asked to have a lymph node biopsy (removal of a few lymph nodes) to examine the effects of the dendritic cells. Some patients may also receive injections of a drug to boost white cell production. Phase(s): Phase II Study Type: Interventional
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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001825 •
Comparison Study of MDX-010 (CTLA-4) Alone and Combined with DTIC in the Treatment of Metastatic Melanoma Condition(s): Melanoma Study Status: This study is completed. Sponsor(s): Medarex Purpose - Excerpt: The objectives of this study are to determine the safety and activity profile of multiple doses of MDX-010, and to determine the whether the addition of cytotoxic chemotherapy (decarbazine [DTIC]) can augment the effects of MDX-010 in patients with chemotherapy naïve metastatic melanoma with a tolerable toxicity profile. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00050102
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Detection of Melanoma Markers in Lymph Nodes or Peripheral Blood of Patients With Melanoma Condition(s): stage I melanoma; stage II melanoma; stage III melanoma; Stage IV Melanoma Study Status: This study is suspended. Sponsor(s): University of Chicago Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Diagnostic procedures may improve the ability to detect the presence or recurrence of disease. PURPOSE: Diagnostic trial to detect melanoma markers in the lymph nodes or peripheral blood of patients who have melanoma. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004153
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Flt3L and CD40L to Treat Metastatic Melanoma and Kidney Cancer Condition(s): Melanoma; Renal Cancer Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: The purpose of this study is to find the largest dose of CD40 L that can be given safely with Flt3L in patients with kidney cancer or metastatic melanoma (melanoma that has spread beyond the original site). Each drug alone has been used safely, but the two have not been used in combination before this study. Flt3L increases the number of a type of immune cell called dendritic cells, which are known to enhance the immune response. CD40L works to activate the response of these cells. Patients 16 years of age and older with metastatic melanoma or kidney cancer that cannot be cured with conventional treatments such as surgery, radiation therapy and chemotherapy may
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be eligible for this study. Candidates will be screened with a physical examination, blood and urine tests, chest X-ray, electrocardiogram, and X-rays and scans to evaluate disease status. Participants will have an injection of Flt3L under the skin every day for 14 days. (Patients or a caregiver will be taught how to administer the injections.) On the 12th day of treatment, patients will also begin receiving CD40L under the skin, for 5 days. If the patients starting at this lowest dose of CD40L do not experience any significant side effects, the dose will be increased for the next group of patients. The dose will be increased a third time if patients in the second group do not have significant side effects. The treatment cycle may be repeated after 28 days from the start of the injections. Patients will undergo leukapheresis to collect white blood cells before beginning treatment and again around day 17. For this procedure, whole blood is collected through a needle placed in an arm vein. The blood circulates through a machine that separates it into its components. The white cells are then removed, and the red cells, platelets and plasma are returned to the body through a second needle placed in the other arm. Patients will be evaluated with a physical examination, X-rays and scans after two cycles for the response to treatment. Patients whose tumors shrink and patients with a mixed response (i.e., some tumors shrink and others enlarge) may be offered up to a total of 6 treatment cycles. Patients whose disease remains stable or worsens will stop Flt3L and CD40 and may be offered treatment with interleukin-2, a substance that may boost the body's immune response to the tumor. Patients will have frequent blood tests. Some patients may have a skin biopsy to evaluate the effects of Flt3L and CD40L. For the biopsy, a small area of skin is numbed with an anesthetic and less than one-quarter inch of skin is removed for study under the microscope. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012532 •
gp100 and MART-1 Peptide Vaccine for Metastatic Ocular Melanoma Condition(s): Melanoma Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will examine the effectiveness and side effects of an experimental vaccine to treat ocular metastatic melanoma. melanoma tumors produce proteins called gp100 and MART-1. Vaccination with specific pieces of these proteins (peptides) may boost the immune system's fight against the cancer. The vaccine injections are mixed with an oil-based substance called Montanide ISA-51, which is intended to increase the immune response to the peptide. Patients 16 years of age and older with progressive metastatic ocular melanoma and for whom standard treatments no longer work may be eligible for this study. Candidates will be screened with a complete physical and examination, including an eye examination, blood and urine tests, chest X-ray, electrocardiogram, X-ray and nuclear medicine imaging scans to evaluate the size and extent of tumor, and, if needed, a cardiac stress test and lung function test. In addition, patients will be tested for their HLA tissue type; patients must be type HLA-A*0201, the type on which this vaccine is based. Participants will receive two injections of both peptide vaccines (a total of four shots) in the thigh each week for 4 weeks. Some patients may undergo a biopsy -surgical removal of a small piece of tissue under local anesthetic-of normal skin and tumor or lymph node tissue to examine the
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effects of the vaccines on the tumor immune cells. Patients will also undergo plasmapheresis-a procedure to collect white blood cells-before treatment begins, after the second vaccination and 3 weeks after the fourth vaccination. For this procedure, blood is drawn through a needle in the arm, similar to donating blood. The blood goes through a machine that separates out the white cells (immune system cells), and the rest of the blood is returned through a needle in the other arm. Patients return for follow-up 3 to 4 weeks after the fourth injection. Patients in whom disease has not progressed or whose tumor has shrunk may receive additional 4-week treatment courses for up to 6 courses (24 immunizations). Patients whose tumor has not responded to therapy and who are physically eligible to receive a substance called interleukin-2 (IL-2) may receive a second series of vaccines together with this agent. IL-2 may boost the immune response to the peptides. It is given intravenously (through a small tube placed in a vein) every 8 hours for 5 days after each vaccination. Patients who respond to the vaccine and IL-2 may be offered additional courses of this treatment regimen. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00009516 •
Pyrazoloacridine in Treating Patients With Metastatic Skin or Eye Melanoma Condition(s): ciliary body and choroid melanoma, medium/large size; Stage IV Melanoma; extraocular extension melanoma; recurrent intraocular melanoma; iris melanoma; Recurrent Melanoma; ciliary body and choroid melanoma, small size Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI); Sidney Kimmel 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 pyrazoloacridine in treating patients who have metastatic skin or eye melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003802
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Stem Cell Transplant for Malignant Melanoma Condition(s): Graft vs Host Disease; Melanoma; Neoplasm Metastasis Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Malignant melanoma is an uncontrolled growth of melanocytes, the cells which normally give pigment to the skin. These cancerous cells can spread (metastasize) from the original kidney tumor site to other organs such as the bones, lymph nodes, liver, lungs, and brain. Once these organs become involved, the uncontrolled growth of cells can lead to organ failure and death. There are several treatments available for malignant melanoma that can be successful. However, once malignant melanoma has spread to other organs, it is rarely curable. Surgery can be
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used to treat malignant melanoma but in many patients the disease has spread too much to be removed by surgery. Medical treatment with chemotherapy can be used to treat malignant melanoma, but it has been relatively unsuccessful for patients whose cancer has spread to other organs. Autologous bone marrow transplants (BMT) have been studied for the treatment of metastatic melanoma. This form of therapy is where marrow cells or stem cells are collected from the patient and used to rescue bone marrow function after very high doses of chemotherapy. The effects of this kind of therapy do not last long and do offer any survival advantage over treat with standard chemotherapy. Allogenic bone marrow transplants (BMT) have been used to treat cancers of the blood and bone marrow. Allogenic transplants are cells collected from relatives of the patient. However, allogenic BMTs are usually combined with powerful doses of chemotherapy and radiation therapy. These additional treatments are associated with toxic side effects, often making BMTs too dangerous to attempt in many patients. Researchers are interested in learning more about the potential benefits of modified bone marrow transplant (allogenic stem cell transplantation) for patients with advanced malignant melanoma. In this study researchers plan to treat patients with advanced malignant melanoma with transplanted stem cells from a genetically matched brother or sister. These stem cells are healthy cells collected from the bone marrow of the patient's relative. Once the stem cells are transplanted they help to make new blood cells. In addition, immune factors found in the transplant can work to destroy cancerous cells. In order to avoid the toxic side effects normally associated with BMT, the stem cell transplant will be combined with low intensity chemotherapy. The majority of the cancer killing effect will be the responsibility of the stem cell transplant rather than the chemotherapy. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001739 •
Vaccine Plus Interleukin-2 in Treating Patients With Advanced Melanoma Condition(s): Stage IV Melanoma; Recurrent Melanoma Study Status: This study is suspended. Sponsor(s): Cancer and Leukemia Group B; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Vaccines made from a person's cancer cells may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill cancer cells. melanoma vaccine plus interleukin-2 may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of vaccine therapy plus interleukin-2 in treating patients who have advanced melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005949
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Vaccine Therapy in Treating Patients With Melanoma Condition(s): stage I melanoma; stage II melanoma; stage III melanoma Study Status: This study is completed.
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Sponsor(s): National Cancer Institute (NCI); Earle A. Chiles Research Institute 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 regimens of melanoma vaccine in treating patients who have melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003895 •
Vaccine Therapy in Treating Patients With Stage II or Stage III Melanoma That Has Been Surgically Removed Condition(s): stage II melanoma; stage III melanoma Study Status: This study is suspended. Sponsor(s): National Cancer Institute (NCI); Rockefeller University Purpose - Excerpt: RATIONALE: Vaccines made from a person's cancer cells may make the body build an immune response to kill tumor cells. PURPOSE: Randomized phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have stage II or stage III melanoma that has been surgically removed. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00045383
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 “skin 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 SKIN 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 “skin cancer” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on skin cancer, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Skin Cancer By performing a patent search focusing on skin 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 skin cancer: •
Antidiotypic monoclonal antibodies for treatment of melanoma Inventor(s): Ferrone; Soldano (Scarsdale, NY) Assignee(s): New York Medical College (Valhalla, NY) Patent Number: 5,780,029 Date filed: October 27, 1995 Abstract: The invention concerns murine antiidiotypic monoclonal antibodies which are the internal image of determinants recognized by a monoclonal antibody on high molecular weight-melanoma associated antigen (HMW-MAA), antibody derivatives, hybridoma cell lines secreting such antiidiotypic monoclonal antibodies, and processes for the preparation of such antiidiotypic monoclonal antibodies, of their derivatives and of the hybridoma cell lines. The murine antiidiotypic monoclonal antibodies are useful for the determination of antibodies directed against high molecular weight-melanoma associated antigen, for the modulation of the immune response to HMW-MAA and for the treatment of melanoma. Excerpt(s): The invention concerns murine antiidiotypic monoclonal antibodies which are the internal image of determinants recognized by a monoclonal antibody on high molecular weight-melanoma associated antigen (HMW-MAA), antibody derivatives, hybridoma cell lines secreting such antiidiotypic monoclonal antibodies, and processes for the preparation of such antiidiotypic monoclonal antibodies, of their derivatives and of the hybridoma cell lines. The murine antiidiotypic monoclonal antibodies are useful for the determination of antibodies directed against high molecular weight-melanoma associated antigen, for the modulation of the immune response to HMW-MAA and for the treatment of melanoma.... Melanomas are tumors of the skin, less frequently of mucous membranes, some of which are benign. Malignant melanomas are carcinomas of neuroectodermal origin generally derived from melanocytes (pigment-producing cells), sometimes from mucous membranes, the chorioid coat or the meninges. There are several types of malignant melanoma which differ in localization, way of spreading and production of metastases.... Conventional treatment of melanoma includes surgery, radio- or chemotherapy, and the application of biological response modifiers. However, these methods have proved to be insufficient to combat the illness, e.g. to prevent tumor recurrence, and are complicated by a large number of severe side effects. Therefore, it is desirable to develop therapeutic approaches which overcome these drawbacks and can replace or be used in combination with conventional treatment. Web site: http://www.delphion.com/details?pn=US05780029__
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Anti-idiotype monoclonal antibody 1A7 and use for the treatment of melanoma and small cell carcinoma Inventor(s): Chatterjee; Malaya (Lexington, KY), Foon; Kenneth A. (Lexington, KY) Assignee(s): University of Kentucky Research Foundation (Lexington, KY) Patent Number: 5,612,030 Date filed: January 17, 1995
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Abstract: The present invention relates isolation of anti-idiotypic antibody 1A7 raised against anti-GD2 mAb 14G2a and its use for the treatment of melanoma and small cell carcinoma. The antibody may be used as a substitute for isolated purified GD2 antigen in any appropriate application. Excerpt(s): The present invention relates isolation of anti-idiotypic antibody 1A7 raised against anti-GD2mAb 14G2a and its use for the treatment and detection of melanoma and small cell carcinoma.... Monoclonal antibody to the human ganglioside GD.sub.2 antigen, and to other melanoma and small cell lung carcinomas are known. For example, U.S. Pat. No. 4,675,287 to Reisfeld et al. discloses a monoclonal antibody to the human ganglioside GD.sub.2 antigen. This antibody is reactive with melanoma and oat cell lung carcinoma cells. This monoclonal antibody is tolerated by the human immune system and thus human immune system does not remove this antibody by immunoactive mechanisms. International Patent Publication WO 8600909 to Reisfeld, R. A. et al is directed to a "Monoclonal antibody directed to human ganglioside GD.sub.2." This patent is the international patent publication related to U.S. Pat. No. 4,675,287 to Reisfeld et al. described above. More specifically, the publication discloses a nonhuman, mammalian monoclonal receptor produced by a hybridoma formed by fusion of cells from a myeloma cell line and lymphocytes that produce antibodies that react with ganglioside GD.sub.2 from a mammal immunized with a ganglioside GD.sub.2 containing immunogen is disclosed.... U.S. Pat. No. 4,693,966 to Houghton et al. discloses human monoclonal antibodies from lymphocytes of patients with malignant melanoma. The monoclonal antibodies of Houghton et al. specifically bind to antigens found on surfaces of renal, lung and breast cancer cells. The antibody also detects the cytoplasmic antigen expressed by cells of neuroectodermal origin, such as melanoma cells. Web site: http://www.delphion.com/details?pn=US05612030__ •
Antiidiotypic antibodies for high molecular weight-melanoma associated antigen Inventor(s): Murray; Brendan (Nelkenring, CH), Pluschke; Gerd (Merzhausen, DE), Hardman; Norman (Riehen, CH) Assignee(s): Novartis Corporation (Summit, NJ) Patent Number: 5,866,124 Date filed: May 22, 1996 Abstract: The invention concerns antiidiotypic antibodies comprising human constant regions, and murine variable regions bearing the internal image of human high molecular weight-melanoma associated antigen which have the specificity of said antibody. These antiidiotypic monoclonal antibodies have immune-regulatory functions and can therefore be used for diagnostic and therapeutic purposes, such as the treatment of melanoma. Excerpt(s): The invention concerns antiidiotypic monoclonal antibodies comprising human constant regions, and variable regions bearing the internal image of human high molecular weight-melanoma associated antigen (HMW-MAA), and derivatives of said antibodies. The antibodies of the invention and their derivatives are useful for diagnostic, prophylactic and therapeutic purposes, such as the immune therapy of melanoma.... Melanomas are tumors of the skin, less frequently of mucous membranes, some of which are benign. Malignant melanomas are carcinomas of neuroectodermal origin generally derived from melanocytes (pigment-producing cells), sometimes from
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mucous membranes, the chorioid coat or the meninges. There are several types of malignant melanoma which differ in localization, way of spreading and production of metastases.... Conventional treatment of melanoma includes surgery, radio- or chemotherapy, and the application of biological response modifiers. However, these methods have proved to be insufficient to combat the illness, e.g. to prevent tumor recurrence, and are complicated by a large number of severe side effects. Therefore, it is desirable to develop therapeutic approaches which overcome these drawbacks and can replace or be used in combination with conventional treatment. Web site: http://www.delphion.com/details?pn=US05866124__ •
Anti-idiotypic antibodies to human melanoma-associated proteoglycan antigen Inventor(s): Raychaudhuri; Syamal (3716 Carmel View Rd., San Diego, CA 92130) Assignee(s): none reported Patent Number: 5,270,202 Date filed: March 12, 1991 Abstract: This application discloses a novel anti-idiotypic antibody, IMelpg2 and equivalents thereof, as well as, antibody fragments, peptides or antisera capable of reacting with at least one of the idiotopes of: (a) murine monoclonal antibody MEM136 and derivatives thereof; (b) a monoclonal antibody secreted by hybridomas from any species having the same immunological specificity as antibody MEM136; or (c) any polyclonal antibodies from any species having the same immunological specificity as antibody MEM136, wherein (a), (b), or (c) is capable of reacting with a specific determinant (epitope) of a MPG antigen are described, together with their preparation and use in the diagnosis, monitoring and treatment of tumors such as melanoma or other diseased cells that express the MPG epitope recognized by antibody MEM136. Excerpt(s): The present invention relates generally to the development of antibodies that are specifically designed to enhance immunological activity by the host against a tumor. More particularly, the present invention relates to antibody reagents that are directed to antigens expressed on the melanoma cells and are useful in the treatment of patients suffering from melanoma. Such antigens include, the High Molecular Weight-Melanoma Associated Antigen ("HMW-MAA"), also know as the human melanoma-associated proteoglycan ("MPG"). MEM136 is a monoclonal antibody that recognizes an epitope of undefined structure on the MPG antigen.... Accordingly, this invention is in the field of anti-idiotypic antibodies to the anti-MPG antibody MEM136 and its immunological equivalents. The anti-idiotype antibody IMelpg2 (also known as "IM32") to antibody MEM136 has been discovered and evaluated in animal model systems.... This invention also is in the field of diagnosis, monitoring and treatment of tumors, such as melanoma or other diseased cells that express the MPG epitope recognized by antibody MEM136, by the administration and application of such anti-idiotypic antibodies. Web site: http://www.delphion.com/details?pn=US05270202__
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Anti-melanoma antibody MG-21 for diagnosis and therapy of human tumors Inventor(s): Hellstrom; Ingegerd (Seattle, WA), Hellstrom; Karl E. (Seattle, WA) Assignee(s): Oncogen (Seattle, WA) Patent Number: 5,055,559 Date filed: February 20, 1986 Abstract: An antibody MG-21 which is directed against a tumor-associated glycolipid antigen and which is capable of activating serum complement or antibody dependent cellular cytoxicity is described. This antibody finds use in the therapy of cancers particularly melanoma and glioma. Proper administration of the antibody results in lysis of the tumor cells in vivo. Excerpt(s): The present invention involves an antibody MG-21, that is (a) directed against a GD3 glycolipid antigen on the surface of tumor cells, particularly cells from melanomas and gliomas, and (b) capable of both activating complement and mediating an antibody-dependent cellular cytotoxicity resulting in the lysis of the tumor cells to which the antibody binds. The antibody of the present invention can be used in the diagnosis and treatment of tumors.... Tumor cells express certain antigens which are absent from, or present in small amounts on, their normal cellular counterparts. Most of these are differentiation antigens, shared by the tumor and certain embryonic cells. Some of the antigens that appear with sufficient selectivity in tumors may serve as possible targets for therapeutic agents. This has been recently reviewed for malignant melanoma, which is one of the human tumors most studied in this respect (Hellstrom and Hellstrom, in Accomplishments in Cancer Research-194 Prize Year, General Motors Cancer Research Foundation, J. G. Fortner & J. E. Rhoads, eds., J. B. Lippincott Company, Philadelphia 1985, p 216-240), as well as for other tumors (Burchell and Taylor-Papadimitriou, in, R. W. Baldwin and V. S. Byers, eds., Monoclonal Antibodies for Tumor Detection and Drug Targeting, Academic Press, 1985, pp.1-15, Kemshead, ibid, pp. 281-302).... Many antibodies have been made to cell surface antigens that are expressed in greater quantities by human tumors than by normal tissues. It has also been well established that antibodies to cell surface antigens can be cytotoxic to tumor cells in the presence of complement (Hellstrom et al., 1962, Progr. Allergy 9: 158-245), and that some antibodies can mediate antibody-dependent cellular cytotoxicity, (Perlmann et al., 1969, Adv. Immunol. 11: 117-193; MacLennan et al., 1969, Immunol. 17: 897-910; Skurzak et al., 1972, J. Exp. Med. 135: 997-1002; Pollack et al., 1972, Int. J. Cancer, 9: 316-323). In the first case, an appropriate source of complement (generally rabbit or guinea pig), and in the latter case a source of effector cells (generally of mouse origin) is needed. Web site: http://www.delphion.com/details?pn=US05055559__
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Basal cell carcinoma tumor supressor gene Inventor(s): Chenevix-Trench; Georgia (Toowong, AU), Negus; Kylie (Queenslopes, AU), Dean; Michael Carlton (Frederick, MD), Hahn; Heidi Eve (Washington, DC), Wicking; Carol (Auchenflower, AU), Christiansen; Jeffrey (Yeronga, AU), Zaphiropoulos; Peter G (Tullinge, SE), Gailani; Mae R. (Guilford, CT), Shanley; Susan Mary (Norman Park, AU), Chidambaram; Abirami (Frederick, MD), Vorechovsky; Igor (Huddinge, SE), Holmberg-Lindstrom; Erika (Solna, SE), Wainwright; Brandon (Bardon, AU), Bale; Allen E. (Northford, CT), Unden; Anne Birgitte (Huddinge, SE), Toftgard; Rune Carl-Magnus (Skarholmen, SE), Gillies; Susan Alana (Newfarm, AU), Goldstein; Alisa Miriam (Rockville, MD), Gerrard; Bernard (Frederick, MD), Leffell; David J. (New Haven, CT), Pressman; Carol Leah (Houston, TX), Smyth; Ian Mcleod (Fig Tree Pocket, AU) Assignee(s): The United States of America as represented by the Department of Health and (Washington, DC) Patent Number: 6,552,181 Date filed: May 16, 1997 Abstract: This invention provides for a tumor suppressor gene inactivation of which is a causal factor in nevoid basal cell carcinoma syndrome and various sporadic basal cell carcinomas. The NBCCS gene is a homologue of the Drosophila patched (ptc) gene. Excerpt(s): This invention pertains to the field of oncology. In particular, this invention pertains to the discovery of a tumor suppressor gene implicated in the etiology of nevoid basal cell carcinoma syndrome (NBCCS) and various cancers including basal cell carcinomas.... Many cancers are believed to result from a series of genetic alterations leading to progressive disordering of normal cellular growth mechanisms (Nowell (1976) Science 194:23, Foulds (1958) J. Chronic Dis. 8:2). In particular, the deletion or multiplication of copies of whole chromosomes or chromosomal segments, or specific regions of the genome are common (see, e.g., Smith et al. (1991) Breast Cancer Res. Treat. 18: Suppl. 1: 5-14; van de Vijer & Nusse (1991) Biochim. Biophys. Acta. 1072: 33-50; Sato et al. (1990) Cancer. Res. 50: 7184-7189). In particular, the amplification and deletion of DNA sequences containing proto-oncogenes and tumor-suppressor genes, respectively, are frequently characteristic of tumorigenesis. Dutrillaux et al. (1990) Cancer Genet. Cytogenet. 49: 203-217.... One cancer-related syndrome that appears to have a strong genetic base is the nevoid basal cell carcinoma syndrome (NBCCS). The nevoid basal cell carcinoma syndrome, also known as Gorlin syndrome and the basal cell nevus syndrome, is an autosomal dominant disorder that predisposes to both cancer and developmental defects (Gorlin (1995) Dermatologic Clinics 13: 113-125). Its prevalence has been estimated at 1 per 56,000, and 1-2% of medulloblastomas and 0.5% of basal cell carcinomas (BCCs) are attributable to the syndrome (Springate (1986) J. Pediatr. Surg. 21: 908-910; Evans et al. (1991) British J. Cancer. 64: 959-961). In addition to basal cell carcinomas (BCCs) and medulloblastomas, NBCCS patients are also at an increased risk for ovarian fibromas, meningiomas, fibrosarcomas, rhabdomyosarcomas, cardiac fibromas and ovarian dermoids (Evans et al. (1991) supra., Evans et al. (1993) J. Med. Genet. 30: 460-464; Gorlin (1995) supra.). Web site: http://www.delphion.com/details?pn=US06552181__
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Combination therapy of IL-2 and DTIC for the treatment of melanoma Inventor(s): Bradley; Edward C. (Moraga, CA), Paradise; Carolyn M. (Emeryville, CA) Assignee(s): Cetus Corporation (Emeryville, CA) Patent Number: 5,066,489 Date filed: July 24, 1990 Abstract: Therapeutic treatment of malignant melanoma in humans is disclosed wherein a synergistically effective amount of DTIC in combination with IL-2 is administered to an individual having such cancer. Excerpt(s): This invention relates to the field of medical treatment. More particularly, this invention is directed to a method for treating malignant melanoma using a combination of IL-2 and DTIC (dimethyl-triazeno-imidazole-carboxmide).... Melanoma in its advanced stages is an incurable disease. Seventy-five percent of skin cancer deaths in the United States are due to malignant melanoma (Cancer Manual, Sixth Edition, (1982), American Cancer Society, Boston, p. 104). Worldwide, the incidence has been rising sharply doubling, every decade over the past 30 years.... Surgery is the only curative therapy for melanoma in its early stages, although this modality, if used aggressively for local recurrence or metastatic disease to regional nodes, is associated with only a 20-30% cure rate. The role of surgery in advanced diseases is palliative. Web site: http://www.delphion.com/details?pn=US05066489__
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Composition and method for treating differentiated carcinoma or melanoma cells with thiapyrylium dyes Inventor(s): Humphlett; Wilbert J. (Rochester, NY), Chen; Lan Bo (Lexington, MA) Assignee(s): Dana Farber Cancer Institute (Boston, MA) Patent Number: 4,774,250 Date filed: April 2, 1987 Abstract: There are described an anti-cancer composition and a method of treating differentiated carcinomas or melanoma, Featuring a suitable carrier and particular 2,4,6tri(aryl or heteroaryl) thiapyrylium dyes. Excerpt(s): This invention relates to a composition and a method for treating cancers involving differentiated carcinomas or melanoma.... It is well-recognized that cancer is a scourge of the modern world, particularly of the developed nations. According to one estimate, in such countries out of a population of 100,000, up to 20,000 people can be expected to contract cancer and fail to get effective treatment. As reported in Vol. 1 of "Dynamics and Opportunities in Cancer Management" by SRI International (1985), page 6, about 5 million persons are likely to die of cancer in 1986. This is particularly devastating in view of the pain and incapacity which precedes actual death by cancer.... It is not surprising, therefore, that much attention is being given to discovering antitumor agents. The need for effective anti-tumor agents is so well-known that, whenever it is rumored that one has been found, the press and the public clamor for information. Web site: http://www.delphion.com/details?pn=US04774250__
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Compositions and methods for reducing the risk of sunlight and ultraviolet induced skin cancer Inventor(s): Ryan; Clarence A. (Pullman, WA) Assignee(s): Washington State University Research Foundation, Inc. (Pullman, WA) Patent Number: 4,906,457 Date filed: September 6, 1988 Abstract: Compositions and methods for reducing the risk of skin cancer. The novel compositions include at least one effective protease inhibitor. Preferred protease inhibitors include serine protease inhibitors and metallo- protease inhibitors. The protease inhibitors are preferably included in concentrations ranging from approximately 10 picograms to 10 milligrams per milliliter of the skin-applicable topical mixtures. The topical mixtures preferably include a suitable topical vehicle such as a cream, lotion, or ointment. One class of anti-carcinogenic skin treatment compositions of this invention preferably includes the desired protease inhibitors in combination with a suitable sunscreen agent or agents, such as para-amino benzoic acid, to provide particularly advantageous compositions for reducing the risk of sunlight-induced skin cancer. Excerpt(s): The technical field of this invention is compositions and methods for treating skin to reduce the risk of skin cancer caused by sunlight or other sources of ultraviolet radiation.... Skin cancer is a prevalent disease in humans caused by overexposure to ultraviolet radiation from the sun and other sources. It is commonly known that people with dark skin, or skin that easily tans, are less likely to develop skin cancer due to sunlight exposure. This reduced risk of sunlight-induced cancer is apparently due to the protective nature of melanin against ultraviolet light, and the relatively higher concentrations of melanin in the skin of darker skinned peoples. Current methods for reducing the risk of skin cancer caused by sunlight usually involve the control or elimination of sunlight exposure. Examples include mechanical blocking of the sun's rays, or chemical screening of the sun's rays, such as by using the ultraviolet sunscreen ingredient para-amino benzoic acid (PABA). Although such approaches appear to reduce the risk of sunlight and other ultraviolet radiation induced skin cancer, there remains a need for additional methods of treatment, particularly method which are effective for treatment after exposure to the ultraviolet light.... The present invention includes the discovery that at least some types of protease inhibitors can be used in relatively minute concentrations to treat skin and thereby reduce the risk of skin cancer associated with exposure to sunlight. The protease inhibitors can be applied prospectively to interrupt or reverse the biochemical processes in the skin which are caused by sunlight or ultraviolet exposure and that lead to skin cancer. Retrospective application of the protease inhibitors is also effective in reducing the risk of skin cancer. Although the exact mechanism of action is not currently known, it is hypothesized that the protease inhibitors act to inhibit the production of, or the presence or activity of, at least certain types of protease enzymes (proteolytic enzymes) which are contributing factors in sunlight and ultraviolet induced skin cancer initiation. The inhibition or reduction of the protease enzymes, or their activities, reduces the likelihood that a tumorigenic reaction will occur in a cell, or that any tumorigenic reaction will not become effective to cause malignant cell reproduction. The action of the protease inhibitors thus reduce the overall likelihood and rate of sunlight-induced skin cancer in humans. Web site: http://www.delphion.com/details?pn=US04906457__
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Detection of chromosome copy number changes to distinguish melanocytic nevi from malignant melanoma Inventor(s): Pinkel; Daniel (Walnut Creek, CA), Bastian; Boris (San Francisco, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,455,258 Date filed: April 13, 2001 Abstract: The present invention provides for methods of distinguishing melanocytic nevi, such as Spitz nevi, from malignant melanoma. The methods comprise contacting a nucleic acid sample from a patient with a probe which binds selectively to a target polynucleotide sequence on a chromosomal region such as 11p, which is usually amplified in Spitz nevi. The nucleic acid sample is typically from skin tumor cells located within a tumor lesion on the skin of the patient. Using another probe which binds selectively to a chromosomal region such as 1q, 6p, 7p, 9p, or 10q, which usually show altered copy number in melanoma, the method can determine that those tumor cells with no changes in copy number of 1q, 6p, 7p, 9p, or 10q, are not melanoma cells but rather Spitz nevus cells. The finding of amplifications of chromosome 11p would be an additional indication of Spitz nevus. Excerpt(s): The melanocyte can give rise to a plethora of morphologically different tumors. Most of them are biologically benign and are referred to as melanocytic nevi. Examples of melanocytic nevi are congenital nevi, Spitz nevi, dysplastic or Clark's nevi, blue nevi, lentigo simplex, and deep penetrating nevus. Pigmented spindle cell nevus is regarded as a subset of Spitz nevi.... Melanoma refers to malignant neoplasms of melanocytes. Its proper diagnosis and early treatment is of great importance because advanced melanoma has a poor prognosis, but most melanomas are curable if excised in their early stages. While clinicians make the initial diagnosis of pigmented lesions of the skin, pathologists make the final diagnosis. Although, in general the histopathological diagnosis of melanoma is straightforward, there is a subset of cases in that it is difficult to differentiate melanomas from benign neoplasm of melanocytes, which have many variants that share some features of melanomas (LeBoit, P. E. Stimulants of Malignant Melanoma: a Rogue's Gallery of Melanocytic and Non-Melanocytic Imposters, in Malignant Melanoma and Melanocytic Neoplasms, P. E. Leboit, ed. (Philadelphia: Hanley & Belfus), pp. 195-258 (1994)). Even though the diagnostic criteria for separating the many simulators of melanoma are constantly refined, a subset of cases remains, where an unambiguous diagnosis cannot be reached (Farmer et al., Discordance in the Histopathologic Diagnosis of Melanoma and Melanocytic Nevi Between Expert Pathologists, Human Pathol. 27: 528-31 (1996)). The most frequent and important diagnostic dilemma is the differential diagnosis between Spitz nevus, a neoplasm composed of large epithelioid or spindled melanocytes, and melanoma.... Misdiagnosis of Spitz nevus as melanoma and vice versa has been repeatedly reported in the literature (Goldes et al., Pediatr. Dermatol., 1: 295-8 (1984); Okun, M. R. Arch. Dermatol. 115: 14161420 (1979); Peters et al., Histopathology, 10, 1289-1302 (1986)). A retrospective study of 102 melanomas of childhood found that only 60 cases were classified as melanoma by a panel of experts, the majority of the remainder being classified as Spitz nevi (Spatz, S., Int. J. Cancer 68, 317-24 (1996)). The hazard of mistaking a Spitz nevus for melanoma can be severe and traumatic: The patients may be subjected to needless surgery, unable to plan for the future, and psychologically traumatized. For obvious reasons, the misdiagnosis of a melanoma as a benign nevus can have even more dramatic consequences. The presence of this diagnostic gray zone has even led the authors of a review article in the "Continuing Medical Education" section of the Journal of the
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American Association of Dermatology to conclude that Spitz nevus and melanoma may "actually exist on a continuum of disease" (Casso et al., J. Am. Acad. Dermatol., 27, 90113 (1992)). The authors recommended that "treatment include complete excision of al Spitz nevi followed by reexcision of positive margins if present." The need for improved diagnostics for melanocytic neoplasms has led to numerous attempts to improve diagnostic accuracy by the use of markers that could be detected by inmnunohistochemistry. While there have been prior efforts aimed at resolving this problem, none have been satisfactory. For example, even though tests employing markers such as S100, HMB45 are useful in establishing that a poorly differentiated tumor is of melanocytic lineage, adjunctive techniques have been of little help in separating benign from malignant melanocytic lesions. Web site: http://www.delphion.com/details?pn=US06455258__ •
Detection of loss of heterozygosity in tumor and serum of melanoma patients Inventor(s): Hoon; Dave S. B. (Los Angeles, CA) Assignee(s): John Wayne Cancer Institute (Santa Monica, CA) Patent Number: 6,465,177 Date filed: October 26, 1998 Abstract: A method is provided for assessing allelic losses on specific chromosomal regions in melanoma patents. The method relies on the evidence that free DNA may be released in the plasma/serum of cancer patients allowing the detection of DNA with LOH in the plasma/serum of cancer patients by analysis for microsatellite markers. The amount of and specific allelic loss allows a prognosis to be made regarding tumor diagnosis and progression, tumor metastasis, tumor recurrence, and mortality. Excerpt(s): The present invention is related to the fields of molecular biology and oncology and provides methods for diagnosis, staging and monitoring of melanoma patients.... Cancer cells almost invariably undergo a loss of genetic material (DNA) when compared to normal cells. This deletion of genetic material which almost all, if not all, varieties of cancer undergo is referred to as "loss of heterozygosity" (LOH). The loss of genetic material from cancer cells can result in the selective loss of one of two or more alleles of a gene vital for cell viability or cell growth at a particular locus on the chromosome. All genes, except those of the two sex chromosomes, exist in duplicate in human cells, with one copy of each gene (allele) found at the same place (locus) on each of the paired chromosomes. Each chromosome pair thus contains two alleles for any gene, one from each parent. This redundancy of allelic gene pairs on duplicate chromosomes provides a safety system; if a single allele of any pair is defective or absent, the surviving allele will continue to produce the coded protein.... Due to the genetic heterogeneity or DNA polymorphism, many of the paired alleles of genes differ from one another. When the two alleles are identical, the individual is said to be homozygous for that pair of alleles at that particular locus. Alternatively, when the two alleles are different, the individual is heterozygous at that locus. Typically both alleles are transcribed and ultimately translated into either identical proteins in the homozygous case or different proteins in the heterozygous case. If one of a pair of heterozygous alleles is lost due to a deletion of DNA from one of the paired chromosomes, only the remaining allele will be expressed and the affected cells will be functionally homozygous. This situation is termed a "loss of heterozygosity" (LOH) or reduction to homozygosity. Following this loss of an allele from a heterozygous cell, the protein or gene product thereafter expressed will be homogeneous because all of the
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protein will be encoded by the single remaining allele. The cell becomes effectively homozygous at the gene locus where the deletion occurred. Almost all, if not all, cancer cells undergo LOH at some chromosomal regions. Web site: http://www.delphion.com/details?pn=US06465177__ •
Detection of melanoma or breast metastasis with a multiple marker assay Inventor(s): Hoon; Dave S. B. (Los Angeles, CA), Conrad; Andrew J. (Los Angeles, CA), Schmid; Peter (Los Angeles, CA) Assignee(s): NGI/Cancer Tech Company, LLC (Los Angeles, CA) Patent Number: 6,057,105 Date filed: December 9, 1997 Abstract: Methods for detecting metastasis of melanoma and breast cancer cells, detecting subclinical metastasis, and monitoring treatment are disclosed. Kits for use in such methods also are disclosed. The methods provide for the detection of nucleic acids corresponding to multiple melanoma or breast cancer specific markers using template dependent amplification processes. Methods using multiple markers provide increased sensitivity over existing methods. Excerpt(s): The present invention relates generally to the field of cancer diagnostic techniques. In particular, the invention relates to the detection of genetic markers indicative of melanoma or breast cancer cells. In one example, detection of multiple markers is achieved by polymerase chain reaction assay.... Cancers are one of the leading causes of disease, being responsible for 526,000 deaths in the United States each year (Boring et al., 1993). For example, breast cancer is the most common form of malignant disease among women in Western countries and, in the United States, is the most common cause of death among women between 40 and 55 years of age (Forrest, 1990). The incidence of breast cancer is increasing, especially in older women, but the cause of this increase is unknown. Malignant melanoma is another form of cancer whose incidence is increasing at a frightening rate, at least sixfold in the United States since 1945, and is the single most deadly of all skin diseases (Fitzpatrick, 1986).... One of the most devastating aspects of cancer is the propensity of cells from malignant neoplasms to disseminate from their primary site to distant organs and develop into metastases. Despite advances in surgical treatment of primary neoplasms and aggressive therapies, most cancer patients die as a result of metastatic disease. Animal tests indicate that about 0.01% of circulating cancer cells from solid tumors establish successful metastatic colonies (Fidler, 1993). Web site: http://www.delphion.com/details?pn=US06057105__
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Human melanoma cell specific antigens and antibodies Inventor(s): Vielkind; Juergen R. (Vancouver, CA) Assignee(s): University of British Columbia (Vancouver, CA) Patent Number: 5,605,831 Date filed: January 31, 1992 Abstract: Methods and compositions are provided for protecting antigens having a specific epitope associated with Melanoma. The epitope is present in melanoma cells but
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is essentially absent from melanocytes cites or other human tumor cells. The antibody can be used in diagnostic methods for histochemical detection of human melanoma of various progression stages and in treatment of melanoma. Excerpt(s): The subject invention is concerned with the preparation of antibodies, particularly monoclonal antibodies, to a marker for human melanoma and their use in the diagnosis and therapy of melanoma.... Human malignant melanoma arises from a series of stages starting with the harmless mole, going through intermediate stages of radial to invasive growth and ending in the destructive final stage of metastatic melanoma. Melanoma usually resists chemotherapy as well as radiotherapy. Surgery is the most effective treatment. However, for it to be effective, surgery requires early diagnosis which is unfortunately hampered by the lack of accurate markers for melanoma.... Melanoma associated antigens have been found, but they are of little diagnostic value. For example, the nerve growth factor receptor is found in high density on melanoma cells. However, monoclonal anti-nerve growth receptor antibodies are specific for neural crest cell diseases rather than for melanoma alone. Likewise, other melanoma associated antigens against which antibodies have been raised are nonspecific for melanoma cells. Examples are the monoclonal antibodies raised against in vitro grown melanoma cells which are directed against gangliosides or glycoproteins present on the melanoma cells. Both antigens are also found on other cells. Web site: http://www.delphion.com/details?pn=US05605831__ •
Human melanoma specific immunotoxins Inventor(s): Mischak; Ronald P. (Palo Alto, CA), Kawahata; Russell T. (San Francisco, CA), Lee; Howard M. (San Francisco, CA), Spitler; Lynn E. (Tiburon, CA), Scannon; Patrick J. (Davis, CA) Assignee(s): Xoma Corporation (Berkeley, CA) Patent Number: 4,590,071 Date filed: September 25, 1984 Abstract: Conjugates of monoclonal antibodies specific to human melanoma and the A chain of a toxic lectin such as ricin or an equivalent ribosomal inhibiting protein. The conjugate is synthesized by a novel process employing anti-toxic lectin B chain antibodies to remove lectin B chain impurities and provide a highly purified conjugate that is non-toxic to cells other than melanoma. The conjugates are used to treat human melanoma.The hybridomas XMMME-001 and XMMME-002 were deposited with the American Type Culture Collection (A.T.C.C.) on Mar. 26, 1985, and given A.T.C.C. Accession Nos. HB8759 and HB8760, respectively. Excerpt(s): This invention relates to cytotoxic products for the treatment of cancer and, specifically, to cytotoxic products formed by binding the A chain of a toxic lectin or its equivalent, such as the class of materials known as ribosomal inhibiting proteins (RIP), to a human melanoma specific monoclonal antibody; methods for production of such products; and, methods for the use of such products in the treatment of human melanoma.... The use of cytotoxic products in the treatment of cancer is well known. Equally well known are the difficulties associated with such treatment. Of these difficulties, the lack of cancer-specific cytotoxicity has received considerable attention, albeit with marginal success. Cytotoxic products continue to kill cancer cells and normal cells alike. Such non-specificity results in a number of undesirable side effects for patients undergoing cancer chemotherapy with cytotoxic products including nausea,
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vomiting, diarrhea, hemorrhagic gastroenteritis, and hepatic and renal damage. Due to normal cell toxicity, the therapeutic dosage of cytotoxic products has been limited such that cancerous cells are not killed to a sufficient level that subsequently prevents or delays new cancerous growth.... The cytotoxic action of toxic lectins, and especially that of ricin and abrin, has been well studied. It is known that toxic lectins consist of two polypeptide chains, A and B, linked by means of disulfide bridge(s). Cytotoxicity is associated with the A chain and its inhibition of protein synthesis in nucleated cells. The B chain is essentially a delivery vehicle for the A chain. The B chain recognizes polysaccharide units at the surface of cells and creates a high affinity interaction with such units. Once the B chain binds with polysaccharide units at the cell surface, the A chain is incorporated into the cell, block ribosomal protein synthesis and untimately leading to cell death. Web site: http://www.delphion.com/details?pn=US04590071__ •
Isolated nucleic acid molecules which encode a melanoma specific antigen and uses thereof Inventor(s): Pfreundschuh; Michael (Homburg/Saar, DE) Assignee(s): Ludwig Institute for Cancer Research (New York, NY) Patent Number: 6,025,191 Date filed: January 3, 1996 Abstract: The invention involves the isolation of a nucleic acid molecule which encodes a melanoma associated antigen. Cell lines and expression vectors which include this and related sequences, as well as uses of these molecules, are described. Excerpt(s): This invention relates to methodologies for identifying molecules of interest. In particularly preferred embodiments, the invention relates to the identification of molecules associated with pathological conditions such as cancer, (melanoma or renal cancer, e.g.), Hodgkin's Disease, autoimmune diseases and so forth. Also a part of the invention are the isolated molecules found as a result of the inventive method. These molecules include, inter alia, protein-containing molecules, isolated nucleic acid molecules encoding these, and antibodies which specifically bind to the proteincontaining molecules. For convenience, the method described herein will be referred to as "serological fishing".... 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=US06025191__
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Melanoma and prostate cancer specific antibodies for immunodetection and immunotherapy Inventor(s): Vielkind; Juergen R. (Vancouver, CA) Assignee(s): Research Corporation Tech., Inc. (Tucson, AZ) Patent Number: 6,057,116 Date filed: June 2, 1997 Abstract: Methods and compositions are provided for detecting antigens having a specific epitope associated with melanoma and prostatic carcinoma. The epitope is present in melanoma cells and prostatic cancer cells but is essentially absent from melanocytes and normal prostatic tissue. The antibody can be used in diagnostic methods for histochemical detection of human melanoma and prostate carcinoma, of various progression stages and in treatment of melanoma and prostate carcinoma. Excerpt(s): The subject invention is related to the use of antibodies, which bind to a unique peptide obtainable from a Xiphophorus melanoma mrk-receptor tyrosine kinase for the diagnosis and therapy of melanoma and prostate cancer.... The ability to detect and diagnose cancer through the identification of tumor markers is an area of widespread interest. Tumor markers are substances, typically proteins, glycoproteins, polysaccharides, and the like which are produced by tumor cells and are characteristic thereof. Often, a tumor marker is produced by normal cells as well as by tumor cells. In the tumor cells, however, the production is in some way atypical. For example, production of a tumor marker may be greatly increased in the cancer cell. Additionally, the tumor marker may be released or shed into the circulation. Detection of such secreted substances in serum may be diagnostic of the malignancy. Therefore, it is desirable to identify previously unrecognized tumor markers, particularly, tumor markers which are secreted into the circulation and which may be identified by serum assays. It is also desirable to develop methods and compositions which allow determination of the cellular origin of a particular tumor or other proliferative disease, for example by radioimaging techniques. The location of the tumor markers on the surface of the cells, particularly where there is an extracellular domain that is accessible to antibodies (i.e., the domain acts as a receptor for the antibodies), provides a basis for targeting cytotoxic compositions to the receptor. Examples of compositions of interest in such a method include complement fixing antibodies or immunotoxins which bind to the receptor as a means of specifically killing those cells which express the receptor on the cell surface.... Human malignant melanoma arises from a series of stages starting with the harmless mole, going through intermediate stages of radial to invasive growth and ending in the destructive final stage of metastatic melanoma. Melanoma usually resists chemotherapy as well as radiotherapy. Surgery is the most effective treatment. However, for it to be effective, surgery requires early diagnosis which is unfortunately hampered by the lack of accurate markers for melanoma. Melanoma associated antigens have been found, but they are of little diagnostic value. For example, the nerve growth factor receptor is found in high density on melanoma cells. However, monoclonal antinerve growth receptor antibodies are specific for neural crest cell diseases rather than for melanoma alone. Likewise, other melanoma associated antigens against which antibodies have been raised are nonspecific for melanoma cells. Examples are the monoclonal antibodies raised against in vitro grown melanoma cells which are directed against gangliosides or glycoproteins present on the melanoma cells. Both antigens are also found on other cells. Web site: http://www.delphion.com/details?pn=US06057116__
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Melanoma and prostate cancer specific antibodies for immunodetection and immunotherapy Inventor(s): Vielkind; Juergen R. (Vancouver, CA) Assignee(s): Research Corporation Technologies, Inc. (Tuscon, AZ) Patent Number: 6,291,196 Date filed: February 22, 1999 Abstract: Methods and compositions are provided for detecting antigens having a specific epitope associated with melanoma and prostatic carcinoma. The epitope is present in melanoma cells and prostatic cancer cells but is essentially absent from melanocytes and normal prostatic tissue. The antibody can be used in diagnostic methods for histochemical detection of human melanoma and prostate carcinoma, of various progression stages and in treatment of melanoma and prostate carcinoma. Excerpt(s): The subject invention is related to the use of antibodies, which bind to a unique peptide obtainable from a Xiphophorus melanoma mrk-receptor tyrosine kinase for the diagnosis and therapy of melanoma and prostate cancer.... The ability to detect and diagnose cancer through the identification of tumor markers is an area of widespread interest. Tumor markers are substances, typically proteins, glycoproteins, polysaccharides, and the like which are produced by tumor cells and are characteristic thereof. Often, a tumor marker is produced by normal cells as well as by tumor cells. In the tumor cells, however, the production is in some way atypical. For example, production of a tumor marker may be greatly increased in the cancer cell. Additionally, the tumor marker may be released or shed into the circulation. Detection of such secreted substances in serum may be diagnostic of the malignancy. Therefore, it is desirable to identify previously unrecognized tumor markers, particularly, tumor markers which are secreted into the circulation and which may be identified by serum assays. It Is also desirable to develop methods and compositions which allow determination of the cellular origin of a particular tumor or other proliferative disease, for example by radioimaging techniques. The location of the tumor markers on the surface of the cells, particularly where there is all extracellular domain that is accessible to antibodies (i.e., the domain acts as a receptor for the antibodies), provides a basis for targeting cytotoxic compositions to the receptor. Examples of compositions of interest in such a method include complement fixing antibodies or immunotoxins which bind to the receptor as a means of specifically killing those cells which express the receptor on the cell surface.... Human malignant melanoma arises from a series of stages starting with the harmless mole, going through intermediate states of radial to invasive growth and ending in the destructive final stage of metastatic melanoma. Melanoma usually resists chemotherapy as well as radiotherapy. Surgery is the most effective treatment. However, for it to be effective, surgery requires early diagnosis which is unfortunately hampered by the lack of accurate markers for melanoma. Melanoma associated antigens have been found, but they are of little diagnostic value. For example, the nerve growth factor receptor is found in high density on melanoma cells. However, monoclonal antinerve growth receptor antibodies are specific for neural crest cell diseases rather than for melanoma alone. Likewise, other melanoma associated antigens against which antibodies have been raised are nonspecific for melanoma cells. Examples are the monoclonal antibodies raised against in vitro grown melanoma cells which are directed against gangliosides or glycoproteins present on the melanoma cells. Both antigens are also found on other cells. Web site: http://www.delphion.com/details?pn=US06291196__
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Melanoma antigenic peptides Inventor(s): Nicolette; Charles A. (Marlborough, MA) Assignee(s): Genzyme Corporation (Framingham, MA) Patent Number: 6,306,640 Date filed: February 11, 1999 Abstract: Thus, this invention provides novel, synthetic polypeptide vaccines against human melanoma and methods for making these vaccines. Polynucleotides encoding these polypeptides are further provided herein. These compositions are useful as melanoma caccinies and in adoptive immunotherapy. Excerpt(s): This invention relates to the field of human tumor vaccines and in particular, vaccine components useful against human melanoma.... Tumor specific T cells, derived from cancer patients, will bind and lyse tumor cells. This specificity is based on their ability to recognize short amino acid sequences (epitopes) presented on the surface of the tumor cells by MHC class I and class II molecules. These epitopes are derived from the proteolytic degradation of intracellular proteins called tumor antigens encoded by genes that are either uniquely or aberrantly expressed in tumor or cancer cells.... The availability of specific anti-tumor T cells has enabled the identification of tumor antigens and subsequently the generation of cancer vaccines designed to provoke an anti-tumor immune response. Anti-tumor T cells are localized within cancer patients, including in the blood (where they can be found in the peripheral blood mononuclear cell fraction), in ascites fluid in ovarian cancer patients (tumor associated lymphocytes or TALs) or within the tumor itself (tumor infiltrating lymphocytes or TILs). Of these, TILs have been the most useful in the identification of tumor antigens and tumor antigen-derived peptides recognized by T cells. Web site: http://www.delphion.com/details?pn=US06306640__
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Melanoma antigens and their use in diagnostic and therapeutic methods Inventor(s): Kawakami; Yutaka (Rockville, MD), Rosenberg; Steven A. (Potomac, MD) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 5,874,560 Date filed: April 22, 1994 Abstract: The present invention provides a nucleic acid sequence encoding a melanoma antigen recognized by T lymphocytes, designated MART-1. This invention further relates to bioassays using the nucleic acid sequence, protein or antibodies of this invention to diagnose, assess or prognoses a mammal afflicted with melanoma or metastata melanoma. This invention also provides immunogenic peptides derived from the MART-1 melanoma antigen and a second melanoma antigen designated gp100. The proteins and peptides provided can serve as an immunogen or vaccine to prevent or treat melanoma. Excerpt(s): This invention is in the field of prevention and treatment of human cancers. More specifically, this invention relates to genes encoding melanoma antigens recognized by T-Cells and their corresponding proteins and to preventative, diagnostic and therapeutic applications which employ these genes or proteins.... Melanomas are aggressive, frequently metastatic tumors derived from either melanocytes or melanocyte
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related nevus cells ("Cellular and Molecular Immunology" (1991) (eds) Abbas A. K., Lechtman, A. H., Pober, J. S. W. B. Saunders Company, Philadelphia: pages 340-341). Melanomas make up approximately three percent of all skin cancers and the worldwide increase in melanoma is unsurpassed by any other neoplasm with the exception of lung cancer in women ("Cellular and Molecular Immunology" (1991) (eds) Abbas, A. K., Lechtiman, A. H., Pober, J. S. W. B. Saunders Company Philadelphia pages: 340-342; Kirkwood and Agarwala (1993) Principles and Practice of Oncology 7:1-16). Even when melanoma is apparently localized to the skin, up to 30% of the patients will develop systemic metastasis and the majority will die (Kirkwood and Agarwala (1993) Principles and Practice of Oncology 7:1-16). Classic modalities of treating melanoma include surgery, radiation and chemotherapy. In the past decade immunotherapy and gene therapy have emerged as new and promising methods for treating melanoma.... T cells play an important role in tumor regression in most murine tumor models. Tumor infiltrating lymphocytes (TIL) that recognize unique cancer antigens can be isolated from many murine tumors. The adoptive transfer of these TIL plus interleukin-2 can mediate the regression of established lung and liver metastases (Rosenberg, S. A., et al., (1986) Science 233:1318-1321). In addition, the secretion of IFN-.gamma. by injected TIL significantly correlates with in vivo regression of murine tumors suggesting activation of T-cells by the tumor antigens. (Barth, R. J., et al., (1991) J. Exp. Med. 173:647-658). The known ability of tumor TIL to mediate the regression of metastatic cancer in 35 to 40% of melanoma patients when adoptively transferred into patients with metastatic melanoma attests to the clinical importance of the antigens recognized (Rosenberg, S. A., et al., (1988) N Engl J Med 319:1676-1680; Rosenberg S. A. (1992) J. Clin. Oncol. 10:180-199). Web site: http://www.delphion.com/details?pn=US05874560__ •
Melanoma antigens and their use in diagnostic and therapeutic methods Inventor(s): Rosenberg; Steven A. (Potomac, MD), Kawakami; Yutaka (Rockville, MD) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 5,994,523 Date filed: January 16, 1998 Abstract: The present invention provides a nucleic acid sequence encoding a melanoma antigen recognized by T lymphocytes, designated MART-1. This invention further relates to bioassays using the nucleic acid sequence, protein or antibodies of this invention to diagnose, assess or prognoses a mammal afflicted with melanoma or metastata melanoma. This invention also provides immunogenic peptides derived from the MART-1 melanoma antigen and a second melanoma antigen designated gp100. The proteins and peptides provided can serve as an immunogen or vaccine to prevent or treat melanoma. Excerpt(s): This invention is in the field of prevention and treatment of human cancers. More specifically, this invention relates to genes encoding melanoma antigens recognized by T-Cells and their corresponding proteins and to preventative, diagnostic and therapeutic applications which employ these genes or proteins.... Melanomas are aggressive, frequently metastatic tumors derived from either melanocytes or melanocyte related nevus cells ("Cellular and Molecular Immunology" (1991) (eds) Abbas A. K., Lechtman, A. H., Pober, J. S. W. B. Saunders Company, Philadelphia: pages 340-341). Melanomas make up approximately three percent of all skin cancers and the worldwide increase in melanoma is unsurpassed by any other neoplasm with the exception of lung
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cancer in women ("Cellular and Molecular Immunology" (1991) (eds) Abbas, A. K., Lechtiman, A. H., Pober, J. S. W. B. Saunders Company Philadelphia pages: 340-342; Kirkwood and Agarwala (1993) Priciples and Practice of Oncology 7:1-16). Even when melanoma is apparently localized to the skin, up to 30% of the patients will develop systemic metastasis and the majority will die (Kirkwood and Agarwala (1993) Priciples and Practice of Oncology 7:1-16). Classic modalities of treating melanoma include surgery, radiation and chemotherapy. In the past decade immunotherapy and gene therapy have emerged as new and promising methods for treating melanoma.... T cells play an important role in tumor regression in most murine tumor models. Tumor infiltrating lymphocytes (TIL) that recognize unique cancer antigens can be isolated from many murine tumors. The adoptive transfer of these TIL plus interleukin-2 can mediate the regression of established lung and liver metastases (Rosenberg, S. A. , et al., (1986) Science 233:1318-1321). In addition, the secretion of IFN-.gamma. by injected TIL significantly correlates with in vivo regression of murine tumors suggesting activation of T-cells by the tumor antigens. (Barth, R. J., et al., (1991) J. Exp. Med. 173:647-658). The known ability of tumor TIL to mediate the regression of metastatic cancer in 35 to 40% of melanoma patients when adoptively transferred into patients with metastatic melanoma attests to the clinical importance of the antigens recognized (Rosenberg, S. A. , et al., (1988) N Engl J Med 319:1676-1680; Rosenberg S. A. (1992) J. Clin. Oncol. 10:180-199). Web site: http://www.delphion.com/details?pn=US05994523__ •
Melanoma antigens and their use in diagnostic and therapeutic methods Inventor(s): Kawakami; Yutaka (Rockville, MD), Rosenberg; Steven A. (Potomac, MD) Assignee(s): The United States of America as represented by the Department of Health and (Rockville, MD) Patent Number: 6,270,778 Date filed: March 12, 1999 Abstract: The present invention provides a nucleic acid sequence encoding a melanoma antigen recognized by T lymphocytes, designated MART-1. This invention further relates to bioassays using the nucleic acid sequence, protein or antibodies of this invention to diagnose, assess or prognoses a mammal afflicted with melanoma or metastata melanoma. This invention also provides immunogenic peptides derived from the MART-1 melanoma antigen and a second melanoma antigen designated gp100. This invention further provides immunogenic peptides derived from the MART-1 melanoma antigen or gp100 antigen which have been modified to enhance their immunogenicity. The proteins and peptides provided can serve as an immunogen or vaccine to prevent or treat melanoma. Excerpt(s): This invention is in the field of prevention and treatment of human cancers. More specifically, this invention relates to genes encoding melanoma antigens recognized by T-Cells and their corresponding proteins and to preventative, diagnostic and therapeutic applications which employ these genes or proteins.... Melanomas are aggressive, frequently metastatic tumors derived from either melanocytes or melanocyte related nevus cells ("Cellular and Molecular Immunology" (1991) (eds) Abbas A. K., Lechtman, A. H., Pober, J. S. W.B. Saunders Company, Philadelphia: pages 340-341). Melanomas make up approximately three percent of all skin cancers and the worldwide increase in melanoma is unsurpassed by any other neoplasm with the exception of lung cancer in women ("Cellular and Molecular Immunology" (1991) (eds) Abbas, A. K., Lechtiman, A. H., Pober, J. S. W.B. Saunders Company Philadelphia pages: 340-342;
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Kirkwood and Agarwala (1993) Principles and Practice of Oncology 7:1-16). Even when melanoma is apparently localized to the skin, up to 30% of the patients will develop systemic metastasis and the majority will die (Kirkwood and Agarwala (1993) Principles and Practice of Oncology 7:1-16). Classic modalities of treating melanoma include surgery, radiation and chemotherapy. In the past decade immunotherapy and gene therapy-have eterged as new and promising methods for treating melanoma.... T cells play an important role in tumor regression in most murine tumor models. Tumor infiltrating lymphocytes (TIL) that recognize unique cancer antigens can be isolated from many murine tumors. The adoptive transfer of these TIL plus interleukin-2 can mediate the regression of established lung and liver metastases (Rosenberg, S. A., et al., (1986) Science 233:1318-1321). In addition, the secretion of IFN-.gamma. by injected TIL significantly correlates with in vivo regression of murine tumors suggesting activation of T-cells by the tumor antigens. (Barth, R. J., et al., (1991) J. Exp. Med. 173:647-658). The known ability of tumor TIL to mediate the regression of metastatic cancer in 35 to 40% of melanoma patients when adoptively transferred into patients with metastatic melanoma attests to the clinical importance of the antigens recognized (Rosenberg, S. A., et al., (1988) N Engl J Med 319:1676-1680; Rosenberg S. A. (1992) J. Clin. Oncol. 10:180-199). Web site: http://www.delphion.com/details?pn=US06270778__ •
Melanoma antigens and their use in diagnostic and therapeutic methods Inventor(s): Kawakami; Yutaka (Rockville, MD), Rosenberg; Steven A. (Potomac, MD) Assignee(s): The United States of America as represented by the Department of Health and (Washington, DC) Patent Number: 6,537,560 Date filed: May 5, 1998 Abstract: The present invention provides a nucleic acid sequence encoding a melanoma antigen recognized by T lymphocytes, designated MART-1. This invention further relates to bioassays using the nucleic acid sequence, protein or antibodies of this invention to diagnose, assess or prognoses a mammal afflicted with melanoma or metastata melanoma. This invention also provides immunogenic peptides derived from the MART-1 melanoma antigen and a second melanoma antigen designated gp100. This invention further provides immunogenic peptides derived from the MART-1 melanoma antigen or gp100 antigen which have been modified to enhance their immunogenicity. The proteins and peptides provided can serve as an immunogen or vaccine to prevent or treat melanoma. Excerpt(s): This invention is in the field of prevention and treatment of human cancers. More specifically, this invention relates to genes encoding melanoma antigens recognized by T-Cells and their corresponding proteins and to preventative, diagnostic and therapeutic applications which employ these genes or proteins.... Melanomas are aggressive, frequently metastatic tumors derived from either melanocytes or melanocyte related nevus cells ("Cellular and Molecular Immunology" (1991) (eds) Abbas A. K., Lechtman, A. H., Pober, J. S. W. B. Saunders Company, Philadelphia: pages 340-341). Melanomas make up approximately three percent of all skin cancers and the worldwide increase in melanoma is unsurpassed by any other neoplasm with the exception of lung cancer in women ("Cellular and Molecular Immunology" (1991) (eds) Abbas, A. K., Lechtiman, A. H., Pober, J. S. W. B. Saunders Company Philadelphia pages: 340-342; Kirkwood and Agarwala (1993) Principles and Practice of Oncoloqy 7:1-16). Even when melanoma is apparently localized to the skin, up to 30% of the patients will develop
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systemic metastasis and the majority will die (Kirkwood and Agarwala (1993) Principles and Practice of Oncology 7:1-16). Classic modalities of treating melanoma include surgery, radiation and chemotherapy. In the past decade immunotherapy and gene therapy have emerged as new and promising methods for treating melanoma.... T cells play an important role in tumor regression in most murine tumor models. Tumor infiltrating lymphocytes (TIL) that recognize unique cancer antigens can be isolated from many murine tumors. The adoptive transfer of these TIL plus interleukin-2 can mediate the regression of established lung and liver metastases (Rosenberg, S. A., et al., (1986) Science 233:1318-1321). In addition, the secretion of IFN-.gamma. by injected TIL significantly correlates with in vivo regression of murine tumors suggesting activation of T-cells by the tumor antigens. (Barth, R. J., et al., (1991) J. Exp. Med. 173:647-658). The known ability of tumor TIL to mediate the regression of metastatic cancer in 35 to 40% of melanoma patients when adoptively transferred into patients with metastatic melanoma attests to the clinical importance of the antigens recognized (Rosenberg, S. A., et al., (1988) N Engl J Med 319:1676-1680; Rosenberg S. A. (1992) J. Clin. Oncol. 10:180-199). Web site: http://www.delphion.com/details?pn=US06537560__ •
Melanoma associated antigenic polypeptide, epitopes thereof and vaccines against melanoma Inventor(s): Figdor; Carl Gustav (Nijmegen, NL), Adema; Gosse Jan (Nijmegen, NL) Assignee(s): IntroGene B.V. (Leiden, NL) Patent Number: 6,500,919 Date filed: February 15, 1995 Abstract: A melanoma associated antigen known as gp100. Furthermore, peptides derived from the antigen are described. Gp100 and its peptides can be used in vaccines for the treatment of melanoma. Another aspect of the invention is host cells capable of expressing gp100 for the gp100-derived peptides. Furthermore, tumor infiltrating lymphocytes (TIL's) specifically recognizing gp100 are described, as are vaccines with these TIL's. Also disclosed are diagnostics for the detection of melanoma and for the monitoring of vaccination. Excerpt(s): The present invention is concerned with cancer treatment and diagnosis, especially with a melanoma associated antigen, epitopes thereof, vaccines against melanoma, tumor infiltrating T lymphocytes recognizing the antigen and diagnostics for the detection of melanoma and for the monitoring of vaccination.... Tumor cells may emancipate themselves from restrictive growth control by oncogene activation, and/or by the inactivation of tumor suppression genes. The course of tumor progression proceeds by a series of gradual, stepwise changes in different `unit characteristics`, i.e. phenotypic traits, many of which are known to be determined or at least influenced by the altered expression of defined oncogenes and/or tumor suppressive genes. Emancipation of the cell from immunological host restriction may follow multistep pathways similar to the emancipation from growth control.... selective downregulation of certain MHC class I and class II alleles. Web site: http://www.delphion.com/details?pn=US06500919__
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Melanoma cell lines expressing shared immunodominant melanoma antigens and methods of using same Inventor(s): Topalian; Suzanne L. (Brookeville, MD), Pardoll; Drew M. (Brookeville, MD), Jaffee; Elizabeth (Lutherville, MD), Rosenberg; Steven A. (Potomac, MD), Adler; Adam (Pikesville, MD) Assignee(s): The Johns Hopkins Universtiy (Baltimore, MD), The United States of America as represented by the Department of Health and (Washington, DC) Patent Number: 6,187,306 Date filed: August 5, 1997 Abstract: The invention pertains to a method of treating or protecting against melanoma that comprises (a) obtaining a melanoma cell line that expresses one or more shared immunodominant melanoma antigens, (b) modifying the melanoma cell line to render it capable of producing an increased level of a cytokine relative to the unmodified cell line, and (c) administering the melanoma cell line to a mammalian host that has melanoma or is at risk for developing melanoma. Preferably the melanoma cell line is allogeneic and is not MHC-matched to the host. Excerpt(s): The present invention pertains to a method of treating or protecting against melanoma using as a vaccine one or more melanoma tumor cell lines that express multiple immunodominantshared melanoma antigens. In particular, the invention pertains to the method of using an allogeneic melanoma cell line as a vaccine. The present invention also relates to a melanoma cell line that expresses shared immunodominant melanoma antigens, and to a composition comprising cells of the melanoma cell line.... It generally is accepted that tumor cells contain multiple specific alterations in the cellular genome responsible for their cancerous phenotype. These alterations affect the expression or function of genes that control cell growth and differentiation. For instance, typically these mutations are observed in oncogenes, or positive effectors of cellular transformation, such as ras, and in tumor suppressor genes (or recessive oncogenes) encoding negative growth regulators, the loss of function of which results in expression of a transformed phenotype. Such recessive oncogenes include p53, p21, Rb1, DCC, MCC, NFI, and WTI.... Immunotherapy is a potential therapeutic approach for the treatment of cancer. Immunotherapy is based on the premise that the failure of the immune system to reject spontaneously arising tumors is related to the failure of the immune system to appropriately respond to tumor antigens. In a functioning immune system, tumor antigens are processed and expressed on the cell surface in the context of major histocompatibility complex (MHC) class I and II molecules, which, in humans, also are termed "human leukocyte associated" (HLA) molecules. Complexes of MHC class I and II molecules with antigenic peptides are recognized by CD8.sup.+ and CD4.sup.+ T cells, respectively. This recognition generates a set of secondary cellular signals and the paracrine release of specific cytokines or soluble so-called "biological response modifiers", that mediate interactions between cells and stimulate host defenses to fight off disease. The release of cytokines then results in the proliferation of antigen-specific T cells. Web site: http://www.delphion.com/details?pn=US06187306__
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Melanoma detection device Inventor(s): McCracken; Robert (P.O.Box 287, Sand Lake, NY 12153) Assignee(s): none reported Patent Number: 5,369,527 Date filed: December 3, 1992 Abstract: An apparatus and method for detecting indications of skin cancer, includes a magnifying glass for magnifying a lesion on an area of skin to be tested and indicia for determining the presence or absence of skin disease indications. The magnifying glass and the indicia are formed on a clear, flexible plastic sheet. The indicia include a circle for detecting whether the diameter of the lesion indicates the presence of melanoma and a cross for detecting whether the symmetry of the lesion indicates the presence of melanoma. Excerpt(s): The present invention relates generally to cancer detection devices, and more particularly to a device for detecting skin cancer, specifically, melanoma.... Detecting cancer typically requires a series of complicated medical tests, including blood and tissue tests, wherein the number and type of tests are dependent on the type of cancer suspected. However, indications of skin cancer, specifically melanoma, can be detected visually. Such indications include lesions which are larger than a certain size, asymmetrical in shape, have irregular borders and/or consist of multi-colored tissue. In the past, there was no simple, single device to aid a physician in the visual recognition of skin cancer. Thus, to visibly recognize skin cancer and thereby to determine whether further tests were needed, a physician had to view the lesion carefully with a hand-held magnifying glass to determine whether it included irregular borders or multi-colored tissue and then had to measure the diameter and symmetrical properties of the lesion with a separate instrument having some sort of scale or ruler contained thereon. This was typically a very clumsy procedure to perform and, depending on the type of scale used, could be inaccurate. Likewise, for a doctor who was not experienced in detecting indications of melanoma or, for a lay person who was uninformed on the subject, there was no single device having means for measuring and detecting skin disease indications to determine whether diagnosis by an experienced physician was required.... Prior art devices including magnifying glasses are known. For example, a magnifying device having an attached scale for accurately measuring distances is shown in Amstutz, U.S. Pat. No. 1,145,959. Here, a magnifying glass is located above a surface containing a scale such that an object lying on the surface is magnified along with the scale to enable accurate magnified measurements. Other known magnifying devices suitable specifically for magnifying printed material include Brown, U.S. Pat. No. 4,881,334 and Buszek, et al. U.S. Pat. No. 4,940,311. None of these devices, however, includes a magnifying glass and means specifically adapted for the accurate and efficient measurement and detection of skin disease indications. Web site: http://www.delphion.com/details?pn=US05369527__
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Melanoma tumor antigen and autologous antibody Inventor(s): Old; Lloyd J. (New York, NY), Oettgen; Herbert F. (New Canaan, CT), Lloyd; Kenneth O. (Bronx, NY), Livingston; Philip O. (New York, NY), Real; Francisco X. (New York, NY), Mattes; M. Jules (Jamaica Estates, NY), Houghton; Alan N. (New York, NY) Assignee(s): Sloan-Kettering Institute (New York, NY) Patent Number: 4,562,160 Date filed: April 1, 1983 Abstract: The present invention concerns novel immunoprecipitating autologous antibodies which recognize the Class 1 gp90 antigen on melanoma cells. These antibodies, optionally tagged with a chromophoric or radioactive label and immobilized on an inert support, may be used to recognize and isolate the gp90 antigen from melanoma cell extracts. Monoclonal antibodies to melanoma may be screened with the gp90 antigen for those which recognize epitopes other than the FD antigenic system.The cell line containing the gp90 antigen which has been cultured in vitro is a source of gp90 antigen for generation of monoclonal antibodies which will be useful in analyzing the gp90 antigen for those epitopes which may be of diagnostic value in immunoassay of melanoma. Excerpt(s): The main questions in human tumor immunology continue to be whether tumor cells express cell surface antigens absent from all normal cell types and whether the immune system is able to recognize these new antigens and mount an immune response against them.... To answer these questions, the serological response of cancer patients against their tumor cells has been studied by autologous typing, where the patients' sera are tested on the autologous cultured tumor cell line and absorption tests are done to determine the specificity of the reactivity. Autologous typing has been used to study the sera of patients with melanoma, astrocytoma, renal cancer and leukemia. The antigens recognized by the patients' sera can be grouped in three different categories. Class 1 antigens or unique antigens only expressed by the autologous tumor cell line; Class 2 antigens expressed by the autologus tumor and other allogeneic tumor or normal cells of the same type or related embryologic origin (Class 2 antigens turn out to be differentiation antigens); Class 3 antigens widely distributed and found in the autologus tumor and also in allogeneic tumor cell lines and normal cells of varied embryologic origin.... Although all three classes of antigens are of interest because of the ability to be autoimmunogenic, Class 1 antigens are particularly interesting because of their very restricted distribution. Web site: http://www.delphion.com/details?pn=US04562160__
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Melanoma-associated antigens identified by monoclonal antibodies Inventor(s): Khan; Amanullah (Dallas, TX) Assignee(s): Cytoclonal Pharmaceutics, Inc. (Dallas, TX) Patent Number: 5,654,408 Date filed: April 21, 1989 Abstract: A new cell line has been made which is capable of producing an antibody that reacts with melanoma associated tumors cells. Antigens capable of reacting with the new antibody have been isolated and characterized. Methods are disclosed for utilizing
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the antibody and antigen of the present invention and diagnostic procedures for determining the identity and extent of melanoma associated disease. The compositions of the present invention are disclosed to be useful in other immunological proceedures. Excerpt(s): This invention relates to anti-tumor monoclonal antibodies and specifically to a monoclonal antibody which recognizes one or more antigenic sites on human malignant melanoma cells. This invention also relates to a manufactured hybridoma continuous cell line capable of producing said antibody and to the antigen(s) recognizable by said antibody which have been isolated and characterized. This invention further relates to the use of said antibody and/or said antigen for the production of certain other monoclonal or polyclonal antibodies. The antibody and antigen of this invention are also useful in diagnostic methods.... Cancerous diseases are generally manifested by uncontrolled growth of cells that differ from the normal cells of the afflicted animal. Diagnosis and treatment of cancer have long been problematic. The disease is often far advanced before symptoms are evident, making treatment more difficult. In addition, the biopsy method of ascertaining whether cells are malignant requires surgery to remove a tissue sample and highly trained pathologists to observe the tissue under a microscope. Treatment of cancer has been hampered by both lack of adequate early detection methods and lack of selectivity of methods employed. Methods effective to eliminate cancer cells may also be harmful to normal cells. Since cancer cells of one type of disease such as leukemia may differ from cancer cells of other types of disease such as malignant melanoma, treatment could be better tailored to the disease if the technological capability to differentiate cancer cells from normal cells, or among types of cancer cells, existed.... The art has revealed that immunologic differences may exist between cells. The present invention concerns the discovery of an immunologic difference between normal cells and cancer cells that has never before been described and the making of a composition useful for manufacturing antibodies for detecting this difference. Web site: http://www.delphion.com/details?pn=US05654408__ •
Melanoma-inhibiting protein Inventor(s): Bogdahn; Ulrich (Wurzburg, DE), Kaluza; Brigitte (Bad Heilbrunn, DE), Burrner; Reinhard (Bach, DE) Assignee(s): Boehringer Mannheim GmbH (Mannheim, DE) Patent Number: 5,770,366 Date filed: January 19, 1996 Abstract: The invention concerns a melanoma-inhibiting protein, nucleic acid sequences coding for this protein, process for the isolation of this protein as well as its use for the production of a therapeutic agent. Excerpt(s): The invention concerns a melanoma-inhibiting protein (MIA), a nucleic acid which codes for it, a process for the isolation and for the detection of this protein as well as its use for the production of a therapeutic agent.... The regulation of cell growth is controlled by factors which act positively as well as negatively. The factors with a positive effect include the known growth factors such as e.g. epidermal growth factor (EGF), platelet derived growth factor (PDGF), insulin and somatomedins. The factors with a negative i.e. inhibitory activity include, in addition to TGF-.beta. which can act as a growth stimulator as well as a growth inhibitor (Roberts et al., Proc. Natl. Acad. Sci. 82 (1985), 119-123), the endogenous, tumour-inhibiting factors from colon carcinoma cells
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(Levine et al., Cancer Research 45 (1985), 2248-2254), melanomas (Bogdahn et al., Cancer Research 49 (1989), 5358-5363) as well as from healthy epithelial cells from the mammary glands of the rat (Ethier et al., J. Cell. Phys. 142 (1990), 15-20).... Disturbances of this regulatory system such as for example by overproduction of growth factors with a positive action or by a reduced dependence of mutated cells on these growth factors (Rodeck et al., International Journal of Cancer 40 (1987), 687-690) enable tumour cells to proliferate in an uncontrolled manner. The aforementioned tumour-inhibitory factors from various tumour tissues represent interesting compounds which may be able to intervene therapeutically in this impaired regulatory system. It must be possible to provide these factors in large amounts and in reproducible purity for such a therapeutic use. However, for most of these factors only enriched fractions from cell lysates have been described up to now which are not suitable for a therapeutic application due to their complex and sometimes unknown composition and the concomitant nonreproducibility of their production. Web site: http://www.delphion.com/details?pn=US05770366__ •
Metastatic melanoma cell lines from monodelphis domestica for use in anti-cancer agent discovery Inventor(s): Dooley; Thomas P. (San Antonio, TX), Robinson; Edward S. (San Antonio, TX) Assignee(s): Southwest Foundation for Biomedical Research (San Antonio, TX) Patent Number: 5,910,424 Date filed: December 3, 1997 Abstract: A cell line of metastatic, pigmented, malignant melanoma cells made by exposing a litter of Monodelphis domestica suckling young to an accumulated dose of ultraviolet radiation and then continuing the ultraviolet exposure after the young are weaned to induce malignant melanoma tumors and culturing the tumor cells from lymph nodes. This cell line can be used to test anti-cancer agents in vitro. Further this cell line can be injected into Monodelphis domestica suckling young so that tumors develop in the animals, and the anti-cancer agents can be tested in vivo. Excerpt(s): The present invention relates to metastatic, pigmented, malignant melanoma cell lines from Monodelphis domestica for in vitro and in vivo experimental purposes and the methods and apparatus for producing such cell lines.... The incidence of cutaneous malignant melanoma (CMM) is rapidly rising among caucasians and is estimated to affect approximately one of every 100 caucasian Americans within their lifetime. Melanoma results from the oncogenic transformation of the pigment-producing cells of the skin and hair, melanocytes. (Rhodes, et al., JAMA, 258:3146-3154 (1987); Jimbow, et al., Physiology, Biochemistry and Molecular Biology of the Skin, Vol. II, ed. Goldsmith, (New York: Oxford Univ. Press, 1991); Elder and Clark, Pigment Cell, 8:5180 (1987)). Although CMM is easily recognized clinically and treated surgically, this form of skin cancer causes about 6700 deaths each year in the U.S.A., due to the propensity for melanoma to metastasize (NIH Consensus Development Panel on Early Melanoma, JAMA 268:1314-1319 (1992)), thus making it the most serious form of skin cancer. The risk factors for cutaneous melanoma include increased age, race, familial occurrence of this disease, ultraviolet radiation (UVR) exposure, dysplastic nevi, fair skin, among others. (Rhodes, et al. (1987); Jimbow, et al., (1991); Elder and Clark (1987); NIH, et al. (1992); Elwood and Lee., Sem. Oncol., 2:149-154 (1975)). Conventional chemotherapy strategies employing cytotoxic or anti-proliferative agents have not been
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highly successful for the treatment of metastatic melanoma to date. Therefore, oncologists are in need of more effective and safe therapies for the treatment of melanoma.... Several laboratory animal models have been developed to study various aspects of melanoma tumorigenesis, genetics, immunology and therapy (Dooley, Oncol. Res., 6:1-9 (1994)). Although no single animal model perfectly matches the genetic, biochemical, and pathological characteristics of human melanoma, each of the common models has some value in specific research areas for comparative studies relative to human melanoma. The established mammalian models, i.e. rodents (primarily mouse) and pigs (Sinclair swine) have some value in specific areas for comparative studies of human melanoma, but they do not provide a satisfactory match for the genetic, biochemical and pathological characteristics of the human disease. Web site: http://www.delphion.com/details?pn=US05910424__ •
Method and composition for selectively inhibiting melanoma Inventor(s): Pezzuto; John M. (River Forest, IL), DasGupta; Tapas K. (River Forest, IL), Kim; Darrick S. H. L. (Chicago, IL) Assignee(s): The Board of Trustees of the University of Illinois (Urbana, IL) Patent Number: 6,225,353 Date filed: November 10, 1998 Abstract: A composition and method of preventing or inhibiting tumor growth, and of treating malignant melanoma, without toxic side effects are disclosed. Betulinic acid or a betulinic acid derivative is the active compound of the composition, which is topically applied to the situs of tumor. Excerpt(s): This invention relates to compositions and methods of selectively inhibiting tumors and, more particularly, to treating a malignant melanoma using plant-derived compounds and derivatives thereof.... Over the past four decades the incidence of melanoma has been increasing at a higher rate than any other type of cancer. It is now theorized that one in 90 American Caucasians will develop malignant melanoma in their lifetime. While an increasing proportion of melanomas are diagnosed sufficiently early to respond to surgical treatment and achieve a greater than 90% ten-year survival rate, it is estimated that nearly 7,000 individuals suffering from metastatic melanoma will die in the United States this year.... For patients with metastatic melanoma not amenable to surgical extirpation, treatment options are limited. 5-(3,3-Dimethyl-1-triazenyl)-1-Himidaz-ole-4-carboxamide (dacarbazine, DTIC) is the most efficacious single chemotherapeutic agent for melanoma having an overall response rate of 24%. But the duration of response to DTIC is generally quite poor. Combination therapy with other synthetic and recombinant agents, including N,N'-bis(2-chloroethyl)-N-nitrosurea (carmustine, BCNU), cisplatin, tamoxifen, interferon-alpha (INF-.alpha.) and interleukin-2 (IL-2), has a higher response rate (e.g., 30-50%) in some trials, but a durable complete response rate is uncommon and toxicity is increased. Sequential chemotherapy has promise, but, clearly, current treatment options for individuals suffering from metastatic melanoma are unsatisfactory. Web site: http://www.delphion.com/details?pn=US06225353__
Patents 325
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Method and composition for selectively inhibiting melanoma Inventor(s): Kim; Darrick S. H. L. (Chicago, IL), Pezzuto; John M. (River Forest, IL), DasGupta; Tapas K. (River Forest, IL) Assignee(s): The Board of Trustees of the University of Illinois (Chicago, IL) Patent Number: 6,495,600 Date filed: August 9, 2000 Abstract: A composition and method of preventing or inhibiting tumor growth, and of treating malignant melanoma, without toxic side effects are disclosed. Betulinic acid or a betulinic acid derivative is the active compound of the composition, which is topically applied to the situs of tumor. Excerpt(s): This invention relates to compositions and methods of selectively inhibiting tumors and, more particularly, to treating a malignant melanoma using plant-derived compounds and derivatives thereof.... Over the past four decades the incidence of melanoma has been increasing at a higher rate than any other type of cancer. It is now theorized that one in 90 American Caucasians will develop malignant melanoma in their lifetime. While an increasing proportion of melanomas are diagnosed sufficiently early to respond to surgical treatment and achieve a greater than 90% ten-year survival rate, it is estimated that nearly 7,000 individuals suffering from metastatic melanoma will die in the United States this year.... For patients with metastatic melanoma not amenable to surgical extirpation, treatment options are limited. 5-(3,3-Dimethyl-1-triazenyl)-1-Himidazole-4-carboxamide (dacarbazine, DTIC) is the most efficacious single chemotherapeutic agent for melanoma having an overall response rate of 24%. But the duration of response to DTIC is generally quite poor. Combination therapy with other synthetic and recombinant agents, including N,N'-bis(2-chloroethyl)-N-nitrosurea (carmustine, BCNU), cisplatin, tamoxifen, interferon-alpha (INF-.alpha.) and interleukin-2 (IL-2), has a higher response rate (e.g., 30-50%) in some trials, but a durable complete response rate is uncommon and toxicity is increased. Sequential chemotherapy has promise, but, clearly, current treatment options for individuals suffering from metastatic melanoma are unsatisfactory. Web site: http://www.delphion.com/details?pn=US06495600__
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Method and composition for selectively inhibiting melanoma using betalinic acid Inventor(s): Pezzuto; John M. (River Forest, IL), DasGupta; Tapas K. (River Forest, IL) Assignee(s): Board of Trustees of the University of Illinois (Urbana, IL) Patent Number: 5,658,947 Date filed: March 21, 1995 Abstract: A composition and method of inhibiting tumor growth and treating malignant melanoma without toxic side effects are disclosed. Betulinic acid or a betulinic acid derivative is the active compound of the composition, which is topically applied to the situs of tumor. Betulinic acid is obtained by the steps of preparing an extract from the stem bark of Ziziphus mauritiana to mediate selective cytotoxic profile against human melanoma in the subject panel of human cancer cell lines, conducting a bioassaydirected fractionation based on the profile of biological activity using cultured human melanoma cells as the monitor, and obtaining betulinic acid.
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Excerpt(s): This invention relates to compositions and methods of selectively inhibiting tumors and, more particularly, to treating a malignant melanoma using plant-derived compounds.... Over the past four decades the incidence of melanoma has been increasing at a higher rate than any other type of cancer. It is now theorized that one in 90 American Caucasians will develop malignant melanoma in their lifetime. While an increasing proportion of melanomas are diagnosed sufficiently early to respond to surgical treatment and achieve a greater than 90% ten-year survival rate, it is estimated that nearly 7,000 individuals suffering from metastatic melanoma will die in the United States this year.... For patients with metastatic melanoma not amenable to surgical extirpation, treatment options are limited. 5-(3,3-dimethyl-1-triazenyl)-1-H-imidazole-4carboxamide (dacarbazine, DTIC) is the most efficacious single chemotherapeutic agent for melanoma having an overall response rate of 24%. But the duration of response to DTIC is generally quite poor. Combination therapy with other synthetic and recombinant agents, including N,N'-bis(2-chloroethyl)-N-nitrosurea (carmustine, BCNU), cisplatin, tamoxifen, interferon-alpha (INF-.alpha.) and interleukin-2 (IL-2), has a higher response rate (e.g., 30-50%) in some trials, but a durable complete response rate is uncommon and toxicity is increased. Sequential chemotherapy has promise, but, clearly, current treatment options for individuals suffering from metastatic melanoma are unsatisfactory. Web site: http://www.delphion.com/details?pn=US05658947__ •
Method of determining melanoma micrometastasis using tyrosinase Inventor(s): Reintgen; Douglas S. (Tampa, FL) Assignee(s): University of South Florida (Tampa, FL) Patent Number: 6,153,388 Date filed: February 5, 1999 Abstract: A highly sensitive method to detect melanoma micrometastasis by examining lymph nodes for the presence of tyrosinase messenger RNA. In a preferred mode, this is accomplished using the combination of reverse transcription and double round polymerase chain reaction (RT-PCR). The amplified samples are examined on a 2% agarose gel and tyrosinase is seen as a 207 base pair fragment. The lymph nodes examined are determined using pre- and intra- operative node mapping. Excerpt(s): Malignant melanoma is a form of skin cancer that can develop from melanocytes, cells that are capable of forming melanin, a dark-brown to black pigment. Most melanomas develop from a previous mole over a period of several months or years and occur most commonly in fair-skinned people that are intolerant to sunlight. There are several distinct types of melanomas. Prognosis depends on the kind of melanoma, its depth of invasion, its location, and the age and health of the patient.... According to new statistics, malignant melanoma could become a lethal epidemic in the next decade. In 1993, 32,000 people in the United States developed melanoma, and 6,420 died from it. Exactly why the rate of skin cancer is growing so rapidly is not known although accumulating evidence suggests that sun exposure and the thinning ozone layer play a major role.... Patients who receive early diagnosis and treatment have a high chance of survival. Most patients in the early stages of melanoma undergo surgery to remove the primary tumor. Patients with locally advanced or metastatic disease usually also undergo some type of chemotherapy and may also receive radiation therapy although radiation is not usually very effective against melanoma. Other treatments
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include cytotoxic drugs, treatment with immunological substances and autologous (self) bone marrow transplant to enhance the patient's immune system. Web site: http://www.delphion.com/details?pn=US06153388__ •
Method of inhibiting melanoma cells Inventor(s): Irie; Reiko F. (Los Angeles, CA) Assignee(s): Wakunaga Seiyaku Kabushiki Kaisha (Osaka, JP) Patent Number: 5,206,270 Date filed: March 5, 1992 Abstract: A method of inhibiting melanoma cell proliferation in a mammal by administering to the mammal S-allylcysteine or a pharmaceutically acceptable salt thereof. Excerpt(s): This invention relates to the use of S-allylcysteine as an antineoplastic agent. More specifically, it relates to a method of inhibiting the proliferation of certain malignant melanoma cells in a mammal by administering to the mammal the aforeindicated antineoplastic agent.... Garlic products are believed to possess beneficial effects in maintaining good health such as providing resistance to infections, lowering cholesterol levels, detoxifying harmful substances, relieving stress, and enhancing the immune response. For thousands of years they have been part of folk medicine. Certain extract forms of garlic are antibacterial and antifungal, and others are antithrombotic.... Garlic and onion oils have previously been reported to inhibit carcinogenesis in several experimental animal models (S. Belman, Carcinogenesis, 1983, 14, 1063). More specifically, this study reported that garlic and onion oils inhibited the growth of DMBA (7, 12-dimethylbenzenanthracene)-induced or PMA (phorbol-myristate-acetate)promoted skin papillomas in mice, as well as inhibiting the growth of DMBA-induced hamster buccal pouch carcinomas. Web site: http://www.delphion.com/details?pn=US05206270__
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Methods and materials for the diagnosis and treatment of sporadic basal cell carcinoma Inventor(s): Altaba; Ariel Ruiz i (New York, NY) Assignee(s): New York University (New York, NY) Patent Number: 6,238,876 Date filed: June 22, 1998 Abstract: Methods for detection of the onset or presence of sporadic basal cell carcinoma in an animal by measuring for elevated levels of ectopic expression of Gli1 in the animal's epidermal tissue sample suspected of harboring sporadic basal cell carcinoma. Excerpt(s): The present invention relates generally to the diagnosis and treatment of pathologies involving tumor formation and neoplasia, and more particularly to the detection of a condition of skin cancer known as sporadic basal cell carcinoma (BCC), and to the identification of relevant therapeutic agents based on their effect on the level of expression and/or activity of the gene Gli1, as well as to the preparation of therapeutic compositions and methods of use.... Inductive signaling plays a critical role
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in both normal and disease development as developmental pathways that become unregulated in the adult can lead to abnormal patterning, overproliferation and neoplasia. One signaling pathway that is involved in several patterning events during embryogenesis is that triggered by secreted sonic hedgehog (Shh.sup.1-4). Shh binding to the membrane patched (ptc)-smoothened (smo) receptor complex elicits a cascade of cytoplasmic signal transduction events, including the inhibition of protein kinase A (PKA.sup.5-12) that leads to the transcription of the zinc finger transcription factor gene Gli1.sup.11,13. Gli1 is a proto-oncogene first isolated as an amplified gene in a glioma.sup.14 that can transform fibroblasts in cooperation with E1A.sup.15. Gli1 is a member of a family comprising two other related genes: Gli2 and Gli3.sup.16,17. However, only Gli1 has been shown to be a target of Shh and mimic its effects.sup.13. In Drosophila, hedgehog signaling.sup.18 similarly leads to the action of cubitus interruptus (ci), a Gli homolog that activates transcription of hedgehog-target genes.sup.19-23.... One of the processes in which Shh signaling is involved is the differentiation of ventral neural tube cell types acting as a notochord and floor platederived signal.sup.1,4,24-27. Previous work by the applicants herein on the role of sonic hedgehog signaling during neural plate patterning in frog (Xenopus laevis) embryos demonstrated that cells becoming floor plate respond to Shh by expressing Gli1, Pintallavis and HNF-3.beta., critical transcription factors that themselves can induce the differentiation of floor plate cells.sup.13,25,28,29. Web site: http://www.delphion.com/details?pn=US06238876__ •
Methods for determining breast cancer and melanoma by assaying for a plurality of antigens associated therewith Inventor(s): Tureci; Ozlem (Homburg/Saar, DE), Chen; Yao-Tseng (New York, NY), Old; Lloyd J. (New York, NY), Pfreundschuh; Michael (Homburg/Saar, DE), Sahin; Ugur (Homburg/Saar, DE) Assignee(s): Ludwig Institute for Cancer Research (NY) Patent Number: 6,338,947 Date filed: May 25, 2000 Abstract: The invention relates to assays for determining breast cancer or melanoma. It has been found that the accuracy of such assays can be improved by assaying samples for three or more known tumor rejection antigen precursors. For breast cancer, the tumor rejection antigen precursors known as SCP-1, NY-ESO-1, and SSX-2 are assayed. For melanoma, SSX-2, NY-ESO-1, and MAGE-3 are assayed. Additional known tumor rejection antigen precursors can also be determined to confirm the assays. It is preferred to carry these out via polymerase chain reactions. Excerpt(s): This invention relates to the determination of cancer, melanoma and breast cancer in particular. The methods involve assaying for members of the so-called "cancertestis" or "CT" antigen family.... 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
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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=US06338947__ •
Methods for screening for possibility or melanoma in a subject Inventor(s): Pfreundschuh; Michael (Homburg/Saar, DE) Assignee(s): Ludwig Institute for Cancer Research (New York, NY) Patent Number: 6,017,716 Date filed: October 28, 1997 Abstract: This invention involves screening for possibility of melanoma. The screening method relies on the binding of antibodies to protein encoded by a nucleic acid molecule defined by the nuclotide sequence of SEQ ID NO:2. Excerpt(s): This invention relates to methodologies for identifying molecules of interest. In particularly preferred embodiments, the invention relates to the identification of molecules associated with pathological conditions such as cancer, (melanoma or renal cancer, e.g.), Hodgkin's Disease, autoimmune diseases and so forth. Also a part of the invention are the isolated molecules found as a result of the inventive method. These molecules include, inter alia, protein-containing molecules, isolated nucleic acid molecules encoding these, and antibodies which specifically bind to the proteincontaining molecules. For convenience, the method described herein will be referred to as "serological fishing".... 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=US06017716__
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Monoclonal antibodies against melanoma Inventor(s): Albert; Winfried (Eberfing, DE), Endl; Josef (Weilheim, DE), Brandt; Michael (Iffeldorf, DE), Jungfer; Herbert (Starnberg, DE) Assignee(s): Boehringer Mannheim GmbH (Mannheim-Waldhof, DE) Patent Number: 5,610,280 Date filed: March 15, 1994 Abstract: The present invention provides a human monoclonal antibody against melanoma, characterized in that it binds to the gangliosides GM3 and GD3 but essentially does not bind to the gangliosides GM1, GM2, GD1a, GD1b and GD2, the binding of the antibody to the gangliosides having been determined by immune staining after thin layer chromatographic separation of the gangliosides. The present invention also provides a process for the production of human monoclonal antibodies directed against melanoma, wherein, without previous immunization, B-lymphocytes are isolated from a healthy person, the isolated B-lymphocytes are immortalized, antibodies from the immortalized B-lymphocytes are screened by immune-histochemical analysis for binding against melanoma and/or melanoma metastases, the positively reacting Blymphocytes are selected, cultured and monoclonal antibodies obtained therefrom. Excerpt(s): The present invention is concerned with a process for obtaining human antibodies which are directed against melanoma, with the antibodies obtained by the process according to the present invention and with the use thereof.... Melanoma, a tumour of the skin, is an extremely aggressive tumour. Especially metastasing melanoma can scarcely any longer be successfully treated by conventional methods. Therefore, there is a great need to find new therapeutics which can be used for the treatment of melanomas.... Dippold et al., (Proc. Natl. Acad. Sci. USA, 77, 61146118/1980) have reported the production of murine monoclonal antibodies against melanoma. One of the antibodies disclosed therein is directed against the ganglioside GD3. In J. Biol. Chem., 262, 6802-6807/1987 are also described murine monoclonal antibodies against melanoma. These bind equally to GM3 and GM2 but not to GD3. Web site: http://www.delphion.com/details?pn=US05610280__
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Monoclonal antibodies to cell surface antigens of human malignant melanoma Inventor(s): Oettgen; Herbert F. (New Canaan, CT), Dippold; Wolfgang G. (Mainz, DE), Ikeda; Hisami (Asahikawa, JP), Old; Lloyd J. (New York, NY), Lloyd; Kenneth O. (Bronx, NY), Li; Lucy T. C. (New York, NY) Assignee(s): Sloan-Kettering Institute for Cancer Research (New York, NY) Patent Number: 4,808,704 Date filed: May 22, 1986 Abstract: Monoclonal antibody recognizing human melanoma cells, method of production and use. Excerpt(s): The invention described herein was made in the course of work under a grant or award from the Department of Health, Education and Welfare.... The present invention relates to the generation of monoclonal antibodies and their use in identifying or characterizing human malignant melanoma antigens. This is a useful diagnostic tool in the detection of human malignant melanoma as well as the study of the nature of human malignant melanoma. Immunofluorescent or enzymatic tagging agents can be
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bound to the highly specific antibodies provided by this invention, using normal procedures, as required for indexing methods. Cytotoxic agents can also be bound to the highly specific antibodies to produce so called "magic bullet" type therapeutic agents which selectively destroy the cells with which the specific antibody binds.... Other investigators have studied melanoma including Koprowski, et. al. Proc. Natl. Acad. Sci. USA 75, 3405-3409 (1978); Yeh, et al. (proc. Natl. Acad. Sci. USA 76, 2927-2931 (1979) and Woodbury et al. Proc. Natl. Acad. Sci. USA 77, 2183-2187 (1980). (The work of the present invention has also been published and is available in the same Journal i.e. Dippold et al. Proc. Nat'l. Acad. Sci. (1980) 77: 6614-6118 and is hereby incorporated by reference. Of these, the p97 melanoma surface antigen described by Woodbury et al may be related to the gp 95 antigen identified by 6 of the monoclonal antibodies of the invention. Web site: http://www.delphion.com/details?pn=US04808704__ •
Monoclonal antibodies to melanoma cells Inventor(s): Ikeda; Hisami (Asahikawa, JP), Old; Lloyd (New York, NY), Lloyd; Kenneth (Bronx, NY), Albino; Anthony (New York, NY) Assignee(s): Sloan-Kettering Institute for Cancer Research (New York, NY) Patent Number: 5,009,995 Date filed: March 11, 1988 Abstract: This invention relates to monoclonal antibodies recognizing the gp130 antigen of human cells. Monoclonal antibodies which recognize distinct determinants on this antigen and methods of detecting the determinants by immunoassay with the monoclonal antibodies which recognize them are disclosed. The monoclonal antibodies are useful in the detection of the gp130 antigen and human cells including melanoma which contain this antigen. Excerpt(s): This invention relates to an antigen found on human melanoma cells and to antibodies which recognize this antigen. The use monoclonal antibodies in the diagnosis and of melanoma is given.... Serological analysis using mouse monoclonal antibodies has identified a number of cell surface antigens expressed on cultured human melanoma cells (Dippold, W. G., K. O. Lloyd, L. T. C. Li, H. Ikeda, H. F. Oettgen and L. J. Old. 1980, Proc. Nat'l Acad. Sci., U.S.A. 77:6114; Houghton, A. N., M. Eisinger, A. P. Albino, J. G. Cairncross and L. J. Old, 1982, J. Exp. Med. 156:1755; Albino, A. P., K. O. Lloyd, A. N. Houghton, H. F. Oettgenand L. J. Old, 1981, J. Exp. Med. 154:1764)). The ink products of the major histocompatibility complex B, C and D loci) and a variety of differentiation antigen. The detailed structure of most of these antigens, as well their biological functions, remains to be elucidated.... One glycoprotein of 130,000 molecular weight (gp130), first defined by Dippold et al. (Dippold, W. G., K. O. Lloyd, L. T. C. Li, H. Ikeda, H. F. Oettgen and L. J. Old, Supra, and designated gp150, was shown to be present in greatest amounts on cultured human melanoma lines (40/43) and cultures of astrocytoma (7/10) and to a lesser degree on a wide range of other malignant or normal cell types. Web site: http://www.delphion.com/details?pn=US05009995__
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Monoclonal antibodies to novel melanoma-associated antigens Inventor(s): Khan; Amanullah (Dallas, TX) Assignee(s): Wadley Technologies, Inc. (Dallas, TX) Patent Number: 4,851,510 Date filed: November 30, 1984 Abstract: A new cell line has been made which is capable of producing an antibody that reacts with melanoma associated tumors cells. Antigens capable of reacting with the new antibody have been isolated and characterized. Methods are disclosed for the utilizing the antibody and antigen of the present invention and diagnostic procedures for determining the identity and extent of melanoma associated disease. The compositions of the present invention are disclosed to be useful in other immunological procedures. Excerpt(s): This invention relates to anti-tumor monoclonal antibodies and specifically to monoclonal antibody which recognizes one or more antigenic sites on a human malignant melanoma cells. This invention also relates to a manufactured hybridoma continuous cell line capable of producing said antibody and to the antigen(s) recognizable by said antibody which have been isolated and characterized. This invention further relates to the use of said antibody and/or said antigen for the production of certain other monoclonal or polyclonal antibodies. The antibody and antigen of this invention are also useful in diagnostic methods.... Cancerous diseases are generally manifested by uncontrolled growth of cells that differ from the normal cells of the afflicted animal. Diagnosis and treatment of cancer have long been problematic. The disease is often far advanced before symptoms are evident, making treatment more difficult. In addition, the biopsy method of ascertaining whether cells are malignant requires surgery to remove a tissue sample and highly trained Pathologists to observe the tissue under a microscope. Treatment of cancer has been hampered by both lack of adequate early detection methods and lack of selectivity of methods employed. Methods effective to eliminate cancer cells may also be harmful to normal cells. Since cancer cells of one type of disease such as leukemia may differ from cancer cells of othter types of disease such as milignant melanoma, treatment could be better tailored to the disease if the technological capability to differentiate cancer cells from normal cells, or among types of cancer cells, existed.... The art has revealed that immunologic differences may exist between cells. The present invention concerns the discovery of an immunologic difference between normal cells and cancer cells that has never before been described and the making of a composition useful for manufacturing antibodies for detecting this difference. Web site: http://www.delphion.com/details?pn=US04851510__
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Monoclonal antibody 1A7 and use for the treatment of melanoma and small cell carcinoma Inventor(s): Chatterjee; Sunil K. (Lexington, KY), Foon; Kenneth A. (Lexington, KY), Chatterjee; Malaya (Lexington, KY) Assignee(s): The Board of Trustees of the University of Kentucky (Lexington, KY) Patent Number: 6,509,016 Date filed: April 15, 1999
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Abstract: The present invention relates to monoclonal antibody 1A7. This is an antiidiotype produced by immunizing with an antibody specific for ganglioside GD2, and identifying a hybridoma secreting antibody with immunogenic potential in a multi-step screening process. Also disclosed are polynucleotide and polypeptide derivatives based on 1A7, including single chain variable region molecules and fusion proteins, and various pharmaceutical compositions. When administered to an individual, the 1A7 antibody overcomes immune tolerance and induces an immune response against GD2, which comprises a combination of anti-GD2 antibody and GD2-specific T cells. The invention further provides methods for treating a disease associated with altered GD2 expression, particularly melanoma, neuroblastoma, glioma, soft tissue sarcoma, and small cell carcinoma. Patients who are in remission as a result of traditional modes of cancer therapy may be treated with a composition of this invention in hopes of reducing the risk of recurrence. Excerpt(s): In spite of numerous advances in medical research, cancer remains the second leading cause of death in the United States. Traditional modes of clinical care, such as surgical resection, radiotherapy and chemotherapy, have a significant failure rate, especially for solid tumors. Failure occurs either because the initial tumor is unresponsive, or because of recurrence due to regrowth at the original site or metastasis. Cancer remains a central focus for medical research and development.... Under the hypothesis that neoplastic cells are normally regulated by immune surveillance, an attractive approach is to re-focus the immune system in affected individuals back towards the tumor. Many types of cancers should be susceptible to the immune system, because they express unusual antigens that reflect the oncogenic transformation of the cell. Antibodies or T cells directed against a target antigen specifically expressed on tumor cells may be able to recruit immune effector functions, and thereby eliminate the tumor or mitigate the pathological consequences.... There are several potential pitfalls in this approach. The first is that the target tumor antigen may be shed from the cell, and thereby block the approach of tumor-specific immune components. The second is that the expression of the target antigen may be heterologous. In this case, a specific immune response would be ineffective in a substantial subclass of affected individuals, or the risk of escape variants would be high. The third difficulty is that tumor-specific antigens are generally-antigenically related to autoantigens, or comprise autoantigens in an atypical mode of expression. This means that tumor-associated antigens are often poorly immunogenic; perhaps due to an active and ongoing immunosuppression against them. Furthermore, cancer patients tend to be immunosuppressed, and only respond to certain T-dependent antigens. Web site: http://www.delphion.com/details?pn=US06509016__ •
Natural organic tanning sunscreen compositions and methods of treatment, to reduce the risk of skin cancer caused by sunlight and ultraviolet radiation (UVA and UVB) Inventor(s): Simpson; Jewel (150 Tenth St., NE., Atlanta, GA 30309) Assignee(s): Simpson; Jewel (Atlanta, GA) Patent Number: 5,756,099 Date filed: December 14, 1996 Abstract: A composition of a topical natural organic tanning sunscreen having medicinal properties utilized to reduce the risk of skin cancer and sunburn caused by sunlight and ultraviolet radiation (UVA and UVB) exposure. The chemical free tanning sunscreen composition, after application, provides the skin organ with a healthy tan within one to
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two hours when exposed to sunlight. Said composition consists of natural organic agents containing nutrients, minerals, chomophores and antioxidants which can be topically applied on the skin organ. Excerpt(s): A Natural organic sunscreen composition for external application which contains natural organic medicinal properties, (The term "organic" as used herein refers to the fact that no heat or chemical substances have been added to the natural sunscreen composition.),which protects the skin organ from skin cancer, sunburn, photo-aging and resistance from ultraviolet radiation, UVA and UVB rays. The natural organic sunscreen composition provides the exposed skin organ to immediate protection from the sun. The chemical free sunscreen composition provides the average skin types with a healthy tan within one to two hours in the bright sunlight.... People do not have to sunbathe to suffer the negative effects of overexposure to ultraviolet radiation. Much of the skin damage can be done by day-to-day routine activities in the sunlight, because photobiologic reactions occur almost continuously both day and night. Sunlight has two types of harmful ultraviolet rays: UVA and UVB. The UVA rays are the sun's burning rays, the primary causes of sunburn and skin cancer, window glass blocks them. The UVB rays which pass through window glass, penetrate more deeply into the skin and appear to be the culprits in premature wrinkling; they also contribute to sunburn and skin cancer. Some scientists estimate that nearly 75 percent of the sun inflicted skin damage on the average person's skin over a lifetime is the result of just outdoors or sitting by a window. Many epidemiologic studies show a strong relationship between sunlight exposure and skin cancer. Another long-term hazard of ultraviolet radiation is photo-aging, this condition occurs when two types of protein substances clamped together breakdowns and thickens. This is what cause wrinkling. This kind of severe wrinkling is not due to old age but almost exclusively to photo-damage. Photo-damage can cause serious medical problems such as skin cancer.... Sunbathing for hours in the sunlight to acquire an "appealing" tan often results in long term hazards which are potentially dangerous to the human skin. The most common agents for sun protection are sunscreens. The increase in skin cancer over the years have caused the general public to rely heavy in the sunscreen products market. The sunscreen market has grown largely in recent years and new products are introduced annually. Sunscreen agents are commercially available to protect the skin from UVA radiation. In 1978 in writing its Sunscreen Monograph, the FDA established a list of Category I sunscreen products that were grand fathered as `generally recognized as safe and effective.` Some include titanium dioxide and zinc oxide, in addition, to a few others. These agents scatter or reflect ultraviolet radiation. However, sunscreen compositions containing these agents are opaque, generally, unattractive in color, and are viewed as unacceptable for usage on more than just the nose or tops of the ears. Furthermore, these agents are very susceptible to rub-off resulting in little or no protection. The most common agents for sun protection are sunscreens. These agents exert their effects through chemical means, i.e., they absorb ultraviolet radiation, so that it cannot penetrate the dermis. Web site: http://www.delphion.com/details?pn=US05756099__ •
Oligonucleotide treatments and compositions for human melanoma Inventor(s): Zupi; Gabriella (Rome, IT) Assignee(s): Istituto Regina Elena (Rome, IT) Patent Number: 6,080,727 Date filed: March 25, 1997
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Abstract: The invention generally provides for compositions and methods of inhibiting the proliferation of human melanoma cancer cells. By administering a therapeutically effective amount of a c-myc oligonucleotide to a human melanoma cancer cell, melanoma cancer cell proliferation can be arrested or inhibited, metastases reduced from a tumor, and apoptosis induced in melanoma cancer cells. Oligonucleotides that are complementary to c-myc polynucleotides are referred to herein as "c-myc oligonucleotides." A particularly efficacious embodiment of the invention relates to compositions and methods concerning the co-administration of c-myc oligonucleotides and cisplatin. Excerpt(s): The present invention relates to compositions and methods for treating melanoma based on oligonucleotides complementary to c-myc polynucleotides and coadministration of such oligonucleotides with cisplatin.... Melanoma tumors are a growing health concern to millions of people worldwide. Because the growth of tumors is influenced by many factors, including the activation of multiple oncogenes, such as proto-oncogenes, it has been difficult to ascertain the cellular mechanisms underlying cancer cell biology. Consequently, available therapies are limited in their ability to arrest tumor growth from human melanoma cancer cells.... In the case of melanoma, the c-myc proto-oncogene is expressed in human melanoma cancer cells growing as tumors. The contribution of this proto-oncogene to the development of melanoma in humans has remained unelucidated until the present invention. For instance, it has been not understood, until the present invention, whether c-myc expression is necessary for melanoma cancer cell proliferation, whether c-myc expression plays a minor role in melanoma cancer cell proliferation or whether c-myc expression is a result of melanoma cancer cell proliferation rather than the cause the of melanoma cell proliferation. The role of c-myc expression in melanoma metastasis and apoptosis has been also not understood. Nor has the role of c-myc expression been established for the chemoresistance of melanoma to cisplatin. Web site: http://www.delphion.com/details?pn=US06080727__ •
P15 and tyrosinase melanoma antigens and their use in diagnostic and therapeutic methods Inventor(s): Robbins; Paul F. (Silver Spring, MD), Rosenberg; Steven A. (Potomac, MD) Assignee(s): The United States of America as represented by the Secretary, Department (Washington, DC) Patent Number: 5,843,648 Date filed: January 10, 1995 Abstract: The present invention provides a nucleic acid sequence encoding a melanoma antigen recognized by T lymphocytes, designated p15. This invention further relates to bioassays using the nucleic acid sequence, protein or antibodies of this invention to diagnose, assess or prognoses a mammal afflicted with melanoma or metastata melanoma. This invention also provides immunogenic peptides derived from the p15 melanoma antigen and a second melanoma antigen designated tyrosinase. The proteins and peptides provided can serve as an immunogen or vaccine to prevent or treat melanoma. Excerpt(s): This invention is in the field of prevention and treatment of human cancers. More specifically, this invention relates to the p15 gene which encodes melanoma antigens recognized by T-Cells and their corresponding proteins and to preventative,
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diagnostic and therapeutic applications which employ these genes, proteins or peptides. This invention also relates to preventative, diagnostic or therapeutic applications utilizing tyrosinase peptides which encode melanoma antigens.... Melanomas are aggressive, frequently metastatic tumors derived from either melanocytes or melanocyte related nevus cells ("Cellular and Molecular Immunology" (1991) (eds) Abbas A. K., Lechtman, A. H., Pober, J. S. W. B. Saunders Company, Philadelphia: pages 340-341). Melanomas make up approximately three percent of all skin cancers and the worldwide increase in melanoma is unsurpassed by any other neoplasm with the exception of lung cancer in women ("Cellular and Molecular Immunology" (1991) (eds) Abbas, A. K., Lechtiman, A. H., Pober, J. S. W. B. Saunders Company Philadelphia pages: 340-342; Kirkwood and Agarwala (1993) Principles and Practice of Oncoloqy 7:1-16). Even when melanoma is apparently localized to the skin, up to 30% of the patients will develop systemic metastasis and the majority will die (Kirkwood and Agarwala (1993) Principles and Practice of Oncoloqy 7:1-16). Classic modalities of treating melanoma include surgery, radiation and chemotherapy. In the past decade immunotherapy and gene therapy have emerged as new and promising methods for treating melanoma.... T cells play an important role in tumor regression in most murine tumor models. Tumor infiltrating lymphocytes (TIL) that recognize unique cancer antigens can be isolated from many murine tumors. The adoptive transfer of these TIL plus interleukin-2 can mediate the regression of established lung and liver metastases (Rosenberg, S. A., et al., (1986) Science 233:1318-1321). In addition, the secretion of IFN-.gamma. by injected TIL significantly correlates with in vivo regression of murine tumors suggesting activation of T-cells by the tumor antigens. (Barth, R. J., et al., (1991) J. Exo. Med. 173:647-658). The known ability of tumor TIL to mediate the regression of metastatic cancer in 35 to 40% of melanoma patients when adoptively transferred into patients with metastatic melanoma attests to the clinical importance of the antigens recognized (Rosenberg, S. A., et al., (1988) N Enql J Med 319:1676-1680; Rosenberg S. A. (1992) J. Clin. Oncol. 10:180-199). Web site: http://www.delphion.com/details?pn=US05843648__ •
Palladium-109 labeled anti-melanoma monoclonal antibodies Inventor(s): Srivastava; Suresh C. (Setauket, NY), Fawwaz; Rashid A. (Pelham, NY), Ferrone; Soldano (Scarsdale, NY) Assignee(s): The United States of America as represented by the Secretary of Energy (Washington, DC) Patent Number: H819 Date filed: April 30, 1984 Abstract: Palladium-109, a beta-emitting radionuclide, when chelated to anti-melanoma monoclonal antibody demonstrates high uptake in melanoma and thus is useful for tumor therapy. Excerpt(s): Recently, monoclonal antibodies labeled with the radionuclide iodine-131 have been used for the detection of tumors. Goldenberg reported the imaging of tumors using monoclonal antibodies [Journal of Nuclear Medicine, 24, 360-362 (1983)] while Larson, et al. reported melanoma imaging using iodine-131 labeled monoclonal antibodies [Journal of Nuclear Medicine, 24, 123-129 (1983)]. One of the problems that has been encountered with such radionuclide labeled monoclonal antibodies has been that the labeling inactivates the antibody because the radionuclide attaches at or near the antigen-binding sites. One approach to overcoming this problem is to employ bifunctional chelates that are capable of covalently binding to the antibody and also
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complexing with a metallic radionuclide. Krejcarek, et al. discuss the covalent attachment of chelating groups to macromolecules, [Biochemical and Biophysics Research Communications, 77, 581-585 (1977)].... The present invention consists of new radiolabeled monoclonal antibodies, the method of preparing these material, and there use in the radiotherapy of melanoma. More specifically the present invention is directed to the use of anti-melanoma monoclonal antibodies which have been chelate-conjugated and radiolabeled as carriers of radioactivity to the site of a tumor for the purpose of inducing tumor therapy.... The radionuclide employed is palladium-109, which is a predominantly beta-emitting radionuclide with a half-life of 13.4 hours, a beta emission of 1.028 MeV maximum, and a scatter area of 2 mm. Palladium-109 is available in meaningful quantities and can be obtained in almost carrier-free form, a necessity for human application. The palladium-109 that has been used in the experimental work discussed herein has been produced at the High Flux Beam Reactor (HFBR) at Brookhaven National Laboratory. This material exhibits a specific activity at the end of bombardment of approximately 1 Curie per milligram. For future human application, it is intended that the palladium-109 radionuclide will be produced at the Brookhaven Linac Isotope Production Facility (BLIP). The material that will be produced at the BLIP will exhibit higher specific activity and will be essentially carrier free. Web site: http://www.delphion.com/details?pn=US0H819__ •
Pigmentation associated, differentiation antigen of human melanoma and autologous antibody Inventor(s): Lloyd; Kenneth O. (Bronx, NY), Thomson; Timothy M. (New York, NY), Mattes; M. Jules (Jamaica Estates, NY), Old; Lloyd J. (New York, NY) Assignee(s): Sloan-Kettering Institute for Cancer Research (New York, NY) Patent Number: 4,591,572 Date filed: April 1, 1983 Abstract: The present invention concerns an autologous precipitating antibody and the gp70 pigment-associated antigen on melanoma cells which it recognizes. The antibody is useful in detecting pigmented melanoma cells in excised specimen, serum or urine. Excerpt(s): The present invention concerns an antigen associated with pigmented melanoma cells and the autologous antibody which recognizes it.... Sera from tumor patients may contain antibodies reacting with their own tumor cells which may be detected using suitable sensitive serological assays such as the mixed hemadsorption assay (MHA). When the cells and the serum come from the same individual this is known as autologous reactivity; when the serum is tested on cells from a different individual then the reaction is known as an allogeneic reactivity. The analysis of the specificity of antibodies in an autologous reaction is easier than in an allogeneic reaction because reactions with unrelated allogeneic antibodies are eliminated. This approach to study tumor cells (autologous typing) has led to the detection of a number of antigens of melanoma and other tumors that have very restricted distributions.... One approach in the search for human tumor-associated antigens has been to test sera from tumor patients for reactivity against the autologous tumor cell line. A possible disadvantage of this approach is that antigens which elicit cellular immunity but not antibodies will not be detected. This point is significant since in animal models tumor-specific transplantation antigens, which elicit strong cell-mediated immunity, do not in general induce antibodies. Still if antibodies reacting with autologous tumor cells are found, they provide a reagent that can be tested for specificity with a thoroughness not readily
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attainable using assays for T cell immunity. Several interesting antibodies have been defined by this approach. Some of these unique antigens are found only on an individual tumor; they have been designated Class 1 antigens. A detailed biochemical characterization of these antigens has been difficult due to the fact that none could be detected by immunoprecipitation. Thus antibodies to the Class 1 antigen AU have been found in serum of patient AU (Carey, et al. Proc. Nat'l. Acad. Sci., U.S.A., 73:3278 (1976)), but characterization of the antigen has been difficult since the antibodies are non-precipitating. Accordingly, efforts have been exerted to locate precipitating autologous antibodies to tumors. Web site: http://www.delphion.com/details?pn=US04591572__ •
Polynucleotides related to monoclonal antibody 1A7 and use for the treatment of melanoma and small cell carcinoma Inventor(s): Chatterjee; Malaya (Lexington, KY), Foon; Kenneth A. (Lexington, KY), Chatterjee; Sunil K. (Lexington, KY) Assignee(s): Board of Trustees of the University of Kentucky (Lexington, KY) Patent Number: 5,935,821 Date filed: November 21, 1996 Abstract: The present invention relates to monoclonal antibody 1A7. This is an antiidiotype produced by immunizing with an antibody specific for ganglioside GD2, and identifying a hybridoma secreting antibody with immunogenic potential in a multi-step screening process. Also disclosed are polynucleotide and polypeptide derivatives based on 1A7, including single chain variable region molecules and fusion proteins, and various pharmaceutical compositions. When administered to an individual, the 1A7 antibody overcomes immune tolerance and induces an immune response against GD2, which comprises a combination of anti-GD2 antibody and GD2-specific T cells. The invention further provides methods for treating a disease associated with altered GD2 expression, particularly melanoma, neuroblastoma, glioma, soft tissue sarcoma, and small cell carcinoma. Patients who are in remission as a result of traditional modes of cancer therapy may be treated with a composition of this invention in hopes of reducing the risk of recurrence. Excerpt(s): In spite of numerous advances in medical research, cancer remains the second leading cause of death in the United States. Traditional modes of clinical care, such as surgical resection, radiotherapy and chemotherapy, have a significant failure rate, especially for solid tumors. Failure occurs either because the initial tumor is unresponsive, or because of recurrence due to regrowth at the original site or metastasis. Cancer remains a central focus for medical research and development.... Under the hypothesis that neoplastic cells are normally regulated by immune surveillance, an attractive approach is to re-focus the immune system in affected individuals back towards the tumor. Many types of cancers should be susceptible to the immune system, because they express unusual antigens that reflect the oncogenic transformation of the cell. Antibodies or T cells directed against a target antigen specifically expressed on tumor cells may be able to recruit immune effector functions, and thereby eliminate the tumor or mitigate the pathological consequences.... There are several potential pitfalls in this approach. The first is that the target tumor antigen may be shed from the cell, and thereby block the approach of tumor-specific immune components. The second is that the expression of the target antigen may be heterologous. In this case, a specific immune response would be ineffective in a substantial subclass of affected individuals, or the
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risk of escape variants would be high. The third difficulty is that tumor-specific antigens are generally antigenically related to autoantigens, or comprise autoantigens in an atypical mode of expression. This means that tumor-associated antigens are often poorly immunogenic; perhaps due to an active and ongoing immunosuppression against them. Furthermore, cancer patients tend to be immunosuppressed, and only respond to certain T-dependent antigens. Web site: http://www.delphion.com/details?pn=US05935821__ •
Polyvalent melanoma vaccine Inventor(s): Morton; Donald L. (24752 Malibu Rd., Malibu, CA 90265) Assignee(s): none reported Patent Number: 5,882,654 Date filed: October 14, 1992 Abstract: A new polyvalent melanoma cell vaccine is disclosed comprised of one or more allogeneic melanoma cell lines which contain effective concentrations of melanoma associated antigens. Further disclosed are a method of stimulating an immunological response by administering the described vaccine as well as a method of prognosticating a patient. Excerpt(s): This invention relates to polyvalent melanoma cell vaccines comprised of allogeneic melanoma cell lines which contain high concentrations of antigens which are immunogenic in melanoma patients.... The concept of using vaccines to induce specific immunity against cancer has existed since the turn of the century, when cancer therapists were first attracted by the success of vaccines in inducing active immunity against infectious diseases. Cancer vaccines differ from vaccines against infectious diseases in that they are administered as therapy after the advent of disease, rather than prophylactically before the disease develops. The theory behind vaccines for cancer and infectious diseases is, however, similar. Both seek to stimulate the patient's own immune system to fight the disease through the introduction of killed whole organisms or cells, specific subcellular antigens, and non-pathologic strains of living organisms or tumor cells. Morton, Sem Oncol 1986; 13(2):180-185.... Early attempts to induce tumor regression in cancer patients by immunizing them with their own tumors or with those from other patients were not properly evaluated; they lacked suitable controls and immunologic studies to determine whether the patients had actually been successfully immunized. However, there are well-documented instances of vaccine-induced immunity against cancer in animal models and evidence for serologic and clinical responses in man to suggest that active specific immunotherapy can be developed as a modality of treatment for cancer. Active immunotherapy became a realistic strategy after it was demonstrated that the induction of DCH reactions in certain malignant neoplasms, such as those induced by the intralesional injection of BCG (an attenuated strain of Mycobacterium) resulted in the regression and eradication of the directly injected cutaneous melanoma metastases and occasionally also in the regression of uninjected metastases. These reports rekindled interest in the century-old concept of a vaccine for cancer and revived efforts to find the crucial formulas for effective vaccine therapy. Web site: http://www.delphion.com/details?pn=US05882654__
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Recombinant viruses encoding the human melanoma-associated antigen Inventor(s): Purchio; Anthony F. (Seattle, WA), Hellstrom; Ingegerd (Seattle, WA), Pennathur; Sridhar (Seattle, WA), Hellstrom; Karl E. (Seattle, WA), Hu; Shiu-Lok (Redmond, WA), Rose; Timothy M. (Seattle, WA), Plowman; Gregory D. (Seattle, WA), Estin; Charles D. (Bainbridge Island, WA), Brown; Joseph P. (Seattle, WA) Assignee(s): Oncogen (Seattle, WA) Patent Number: 5,262,177 Date filed: January 27, 1987 Abstract: Peptides or proteins related to a melanoma associated antigen are described. These are produced in large quantities via recombinant DNA techniques and/or by chemical synthetic methods. The peptides or proteins can be used as immunogens in vaccine formulations which can induce an immune response that selectively destroys melanoma cells in a vaccinated individual. Where the peptides or proteins are expressed by a recombinant virus, inactivated or live virus vaccine formulations may be prepared. Excerpt(s): The present invention is directed to vaccine formulations which can induce an immune response that selectively destroys melanoma cells in a vaccinated individual. Accordingly, a peptide or protein related to a melanoma associated antigen is produced in large quantities via recombinant DNA techniques and/or by chemical synthetic methods. The peptide or protein of the present invention can be used as an immunogen in a vaccine formulation. In certain embodiments where the peptide or protein related to a melanoma associated antigen is expressed by a recombinant virus, the recombinant virus itself may be used as an immunogen in a vaccine formulation. The invention also provides for processes which include the use of recombinant DNA techniques as well as chemical synthetic methods than enable the production of peptides or proteins related to the melanoma associated antigen in large quantities.... The invention is illustrated by way of example using as immunogens peptides related to p97, a monomeric cell surface sialoglycoprotein with an apparent molecular weight of slightly less than 97,000 daltons which is a cell surface component of melanoma cells.... Work with experimental animals, particularly rodents, has shown that most tumors induced by oncogenic viruses express antigens encoded by the viral genome, and that immunization with these antigens can lead to rejection of a subsequent challenge of tumor cells induced by the same virus. Although much of this work was one with laboratory strains of virus, such as SV40, polyoma virus, and Friend, Moloney, or Rauscher murine leukemia viruses, horizontal and vertical transmission of oncogenic viruses in nature have been demonstrated; indeed a commercial vaccine against virus-induced feline leukemia an sarcoma is now available. Web site: http://www.delphion.com/details?pn=US05262177__
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Shed melanoma antigen compositions Inventor(s): Bystryn; Jean-Claude (Department of Dermatology, New York University Medical Center, 560 First, New York, NY 10016) Assignee(s): none reported Patent Number: 5,030,621 Date filed: February 22, 1990
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Abstract: A human anti-cancer vaccine is prepared by culturing human cancer cells, such as human melanoma cells, human lung cancer cells, human colon cancer cells, human breast cancer cells, and other human cancer cells in a serum-free medium. The cells are selected on the basis of expressing different patterns of cell surface tumor antigens and are adapted to and are grown in a serum-free medium. During culturing antigens of the cancer cells are shed into the culture medium. The culture medium, containing the shed cancer cell antigens, is then concentrated, such as by vacuum ultrafiltration. In some instances the vaccine is then treated with a non-ionic surfactant or detergent, such as Nonidet P-40 (NP-40), to break up aggregates and treated with a presevative, such as sodium azide, and then subjected to ultracentrifugation. The supernatant is then dialyzed against normal saline with a small amount of sodium azide and made up to the desired protein concentration by the addition of normal saline and subjected to filtration to remove any microorganisms. When used as an anti-cancer vaccine, the resulting composition is administered to the patients, such as intradermally. In the instance where the patients are cancer patients, the vaccine is administered to the patient intradermally over a period of weeks, with or without an adjuvant, into each of the four extremities at the desired dose, e.g. from an initial dosage of about 0.25 ug/site up to about 50 ug/site. By following the practices of this invention there has been prepared a polyvalent human melanoma antigen vaccine containing multiple melanoma associated antigens (MAAs) and free of detectable fetal calf serum (FCS) proteins and Dr antigens. Excerpt(s): This invention relates to human vaccines, such as vaccines for protection against pathogenic microorganisms, e.g. bacterial infections and the like, and to human anti-cancer vaccines. More particularly, and in one special embodiment, this invention relates to the preparation of human anti-cancer vaccines useful for the prevention and/or treatment of cancer, such as melanoma, breast cancer, colon cancer, lung cancer and other such cancers.... For the treatment of cancer, it has been suggested to increase tumor protective immunity by active immunization to tumor antigens, see (1) the article by R. K. Oldham entitled "Biologicals and Biological Response Modifiers: Fourth Modality of Cancer Treatment", Cancer Treat Rep (1984);68:221-232, and (2) the article by M. J. Mastrangelo et al entitled "Current Condition and Prognosis of Tumor Immuunotherapy: A Second Opinion", Cancer Treat Rep (1984);68:207-219. Unfortunately, this approach for the prevention and/or treatment of cancer has not been successful or completely satisfactory because of a number of problems, such as the absence in the vaccine of tumor antigens expressed by the tumor to be treated, poor characterization of the antigens in tumor vaccines, the contamination of vaccines by immunogenic but undesirable material, such as fetal calf serum (FCS) protein or transplantation antigens and additionally due to the antigenic heterogenicity of the cancer cells. Moreover, such tumor vaccines were often prepared from fresh tumor cells, the supply of which is limited so that the properties of the vaccines are not reproducible.... It is an object of this invention to provide an improved anti-cancer vaccine. Web site: http://www.delphion.com/details?pn=US05030621__
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Thiourea derivatives, methods of their preparation and their use in neutron capture therapy of malignant melanoma Inventor(s): Gabel; Detlef (Bremen, DE) Assignee(s): The United States Department of Energy (Washington, DC) Patent Number: 5,021,572 Date filed: January 27, 1989 Abstract: The present invention pertains to boron containing thiouracil derivatives, their method of preparations, and their use in the therapy of malignant melanoma using boron neutron capture therapy. Excerpt(s): The present invention also relates to methods for the preparation of the compounds of formula I, and their application in neutron capture therapy of malignant melanoma.... Thioureas are known as substances which accumulate in malignant melanoma due to its active melanin synthesis.... Malignant melanoma is a tumor of melanocytes. Its incidence is especially high among the fair-skinned population. In most industrial nations its incidence is increasing. Web site: http://www.delphion.com/details?pn=US05021572__
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Transgenic animal model system for human cutaneous melanoma Inventor(s): Mintz; Beatrice (Elkins Park, PA) Assignee(s): Fox Chase Cancer Center (Philadelphia, PA) Patent Number: 5,550,316 Date filed: January 29, 1993 Abstract: The present invention relates to transgenic animal model systems for human cutaneous melanoma. It is based, at least in part, on the discovery that, in susceptible transgenic mice, accelerated formation of melanoma tumors occurred near the wound borders of skin grafts carrying the Tyr-SV40E transgene, indicating that factors present during wound healing facilitate the formation of cutaneous melanoma in susceptible tissue. Excerpt(s): The present invention relates to transgenic animal model systems for human cutaneous melanoma. It is based, at least in part, on the discovery that, in susceptible transgenic mice, accelerated formation of melanoma tumors occurred near the wound borders of skin grafts carrying the Tyr-SV40E transgene, indicating that factors present during wound healing facilitate the formation of cutaneous melanoma in susceptible tissue.... Primary malignant melanoma of the skin is the leading cause of death from any skin disease (see Fitzpatrick et al., 1983, in "Harrison's Principles of Internal Medicine," Edition, Petersdorf et al. eds., McGraw Hill, New York, pp. 836-838). Melanoma has been estimated to account for 1 percent of all skin cancers, with an incidence of approximately 4.5 in 100,000 person-years in Caucasians and 0.6 in 100,000 person years in Blacks in the U.S. (Ibid., p. 368). The incidence of melanoma is higher in light-skinned persons and increases with geographical proximity to the equator (Id.).... Because chemotherapy is frequently ineffective in treating melanoma, and because melanomas have a propensity for metastasis (Foos et al., 1983, in "Intraocular Tumors", eds. Lommatzsch et al., Springer-Verlag, Berlin pp. 51-57), early detection followed by surgical excision is a key element in successful treatment of the disease. The five-year survival decreases in proportion to the depth of tumor invasion (Id.). With less than 0.85
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mm of invasion, the five year survival is about 99 percent; this drops to less than 10 percent in metastatic melanoma. Web site: http://www.delphion.com/details?pn=US05550316__ •
Treatment of basal cell carcinoma and actinic keratosis employing hyaluronic acid and NSAIDs Inventor(s): Falk; Rudolf Edgar (Toronto, CA), Asculai; Samuel Simon (Toronto, CA) Assignee(s): Hyal Pharmaceutical Corporation (Mississauga, CA) Patent Number: 5,639,738 Date filed: February 21, 1992 Abstract: A method of treating a mammal for a condition of the skin or exposed tissue selected from the group consisting of basal cell carcinoma and actinic keratosis is provided. The method consists essentially of topically administering to the site of the condition, more than once per day over a period of days sufficient to treat the condition, a non-toxic effective dosage amount of a composition consisting essentially of(a) a nonsteroidal anti-inflammatory drug (NSAID) in an amount sufficient to block prostaglandin synthesis,(b) hyaluronic acid or a pharmaceutically acceptable salt thereof in an amount effective to transport said NSAID into the skin or exposed tissue at the site of the condition. The concentration of the hyaluronic add or salt thereof is between 1-3% by weight of the composition. The molecular weight of the hyaluronic acid or salt thereof is between 150,000 and 750,000 Daltons. A pharmaceutical excipient suitable for topical application is included. The NSAID in the composition may be diclofenac sodium. Excerpt(s): This invention also relates to formulations suitable for use in such treatments, the use of such formulations in such treatments, methods of such treatment, and the delivery of drugs for such treatments.... Basal cell carcinoma is presently treated by surgery. Each lesion, together with all surrounding and underlying tissue (dermis, epidermis, and subdermis), is cut out. In some instances, surgery, while necessary for the patient's welfare, may put the patient at risk in some other respect (for example, a lesion on a patient's temple whose removal (resection) may jeopardize the patient's health). Squamous cell tumours are also treated the same way as are other forms of cancer in the skin and exposed tissue. Furthermore, other conditions and diseases of the skin and exposed tissue are treated the same way or in ways that cause discomfort to the patient, for example melanoma, genital warts, cervical cancer, HPV (Human Papilloma Virus).... Actinic keratoses lesion is dealt with similarly. Additionally, liquid nitrogen has been used to remove the lesion. Web site: http://www.delphion.com/details?pn=US05639738__
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Treatment of basal cell carcinoma intralesionally with recombinant human alpha interferon Inventor(s): Peets; Edwin A. (New York, NJ), Smiles; Kenneth A. (Windsor, NJ), Tanner; Daniel J. (Brooklyn, NJ) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 5,028,422 Date filed: April 13, 1989 Abstract: This invention relates to a method of treating basal cell carcinoma with purified human recombinant DNA interferon alpha-2, preferably purified human recombinant DNA interferon alpha-2b by administering intralesionally (by injection) to a patient in need of such treatment, a sufficient amount of the purified human recombinant DNA alpha interferon, preferably recombinant DNA interferon alpha-2b, to be effective as an antitumor agent. Excerpt(s): This invention relates to a method of treating basal cell carcinoma with recombinant human alpha interferon by administering the interferon directly into the carcinoma lesion, i.e. intralesionally.... Basal cell carcinomas are the most common cutaneous neoplasms found in humans. The majority of the 500,000 new cases of nonmelanoma skin cancers each year are basal cell carcinomas.... Basal cell carcinomas exist in a variety of clinical and histological forms such as nodular-ulcerative, superficial, pigmented, morphealike, fibroepithelioma and nevoid syndrome. Present treatment methods include various surgical techniques such as electrodesiccation and curettage, excision, cryosurgery and irradiation. Cure rates for the surgical techniques are generally stated to be about 95%. Despite the high cure rates effected by surgical techniques, non-surgical methods of therapy are generally thought to be more desirable. Web site: http://www.delphion.com/details?pn=US05028422__
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Treatment of melanoma using N,N-dimethylglycine Inventor(s): Lawson; John W. (Clemson, SC), Reap; Elizabeth A. (Pendleton, SC), Kendall; Roger V. (Williston, VT) Assignee(s): Foodscience Corporation (Essex Junction, VT) Patent Number: 4,994,492 Date filed: January 9, 1989 Abstract: This invention relates to a method for inhibiting the metastasis or formation of a melanoma tumor by treating the patient with an effective amount of N,NDimethylglycine. Excerpt(s): This invention relates to the use of N,N-dimethylglycine (DMG) to treat melanoma tumors in man or animals.... Dimethylglycine is an intermediary metabolite and amino acid found in low levels in many foods, and is produced in the body from choline. DMG is an endogenous compound and an enzyme system in the body effectively converts the substance into metabolites that are either used by the body or are safely excreted from the body.... A great deal of research has been carried out in recent years on the physiological effects of N,N-dimethylglycine. Web site: http://www.delphion.com/details?pn=US04994492__
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Treatment of melanoma with a vaccine comprising irradiated autologous melanoma tumor cells conjugated to a hapten Inventor(s): Berd; David (Wyncote, PA) Assignee(s): Thomas Jefferson University (Philadelphia, PA) Patent Number: 5,290,551 Date filed: December 4, 1992 Abstract: The invention is a haptenized tumor vaccine for the treatment of cancer. Treatment of cancer patients with an autologous, vaccine preceded by low dose cyclophosphamide (CY) induces delayed-type hypersensitivity (DTH) to melanoma cells, and in some cases, regression of metastatic tumors. The efficiency of the process has been increased by immunizing with tumor cells conjugated to the hapten such as DNP, TNP or AED.Additional embodiments of the vaccine include: 1) combining the vaccine with immunomodulating drugs, such as, interleukin-2 (IL2); and 2) purifying the active components of the vaccine by extracting antigens from cancer cells to produce a chemically-defined, haptenated vaccine. The treatment may also be extended to include other types of human cancer. Excerpt(s): The invention described herein was made in the course of work under a grant or award from an NIH Cancer Research grant.... This invention was disclosed in a Disclosure Document filed Apr. 18, 1990, which is now abandoned.... It was theorized in the 1960's that tumor cells bear specific antigens (TSA) which are not present on normal cells and that the immune response to these antigens might enable an individual to reject a tumor. It was later suggested that the immune response to TSA could be increased by introducing new immunological determinants on cells. Mitchison, Transplant. Proc. 2:92-103 (1970). Such a "helper determinant", which can be a hapten, a protein, a viral coat antigen, a transplantation antigen, or a xenogenous cell antigen, could be introduced into a population of tumor cells. The cells would then be injected into an individual who would be expected to be tolerant to the growth of unmodified tumor cells. Clinically, the hope was that an immunologic reaction would occur against the helper determinants, as a consequence of which the reaction to the accompanying TSA is increased, and tumor cells which would otherwise be tolerated are destroyed. Mitchison (1970) also suggests several modes of action of the helper determinants including 1) that the unmodified cells are merely attenuated, in the sense that their growth rate is slowed down or their susceptability to immunologic attack increased; 2) that helper determinants merely provide points of attack and so enable the modified cells to be killed by an immune response not directed against TSA; 3) that the helper determinants have an adjuvant action such as binding to an antibody or promoting localization of the cells in the right part of the body for immunization, in particular, in lymph nodes. Web site: http://www.delphion.com/details?pn=US05290551__
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Treatment of melanomas with thalidomide alone or in combination with other antimelanoma agents Inventor(s): Andrulis, Jr. Peter J. (Bethesda, MD), Drulak; Murray W. (Gaithersburg, MD) Assignee(s): Andrulis Pharmaceuticals Corp. (Bethesda, MD) Patent Number: 5,731,325 Date filed: June 6, 1995 Abstract: A method for treatment of malignant melanoma by administering an effective amount of thalidomide alone or in combination with other anti-melanoma drugs. Excerpt(s): The present invention is directed to compositions and methods for treating malignant melanoma. In one specific aspect, the present invention is directed to a method for treating melanomas with thalidomide. In another specific embodiment of the invention, melanoma is treated with thalidomide in combination with other antimelanoma drugs.... The present invention also relates to methods of treating melanomas with cytokine/growth factor inhibitors such as those agents inhibitory to basic fibroblast growth factor (bFGF), TNF-alpha, IL-1 and/or melanoma growth stimulatory activity (MGSA) factor as well as pharmaceutical compositions containing relevant cytokine/growth factor inhibitors and/or other anti-melanoma drugs.... Thalidomide was first synthesized and marketed in the 1950's as a sedative. The toxicity of the compound was so low that a dose killing 50% of animals (LD.sub.50) could not be established. Thalidomide was therefore thought to be a safer alternative to barbiturates. In 1961, thalidomide administered to pregnant women resulted in an epidemic of congenial malformations. The incidence of malformed babies paralleled the sales of thalidomide and quickly dropped off when thalidomide was removed from the market. Web site: http://www.delphion.com/details?pn=US05731325__
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Treatment, diagnosis and evaluation of anti-cancer therapy resistance in melanoma Inventor(s): Kerbel; Robert S. (Toronto, CA), Ben-David; Yaacov (Toronto, CA), Pak; Brian J. (Toronto, CA) Assignee(s): Sunnybrook & Women's College Health Sciences Centre (Toronto, CA) Patent Number: 6,573,050 Date filed: October 27, 2000 Abstract: The invention relates to overcoming anti-cancer therapy resistance in melanoma by regulation of the expression of tyrosinase related protein 2 (TYRP2). Treatment of melanoma with anti-cancer therapy may be negatively impacted by anticancer resistance of melanoma cells. Altering expression of TYRP2 in melanoma cells can enhance efficacy of anti-cancer therapies, such as chemotherapy and radiotherapy. Methods for treatment of melanoma are disclosed, as well as methods for diagnosis of anti-cancer therapy resistance, and methods for evaluating candidate anti-cancer therapies for melanoma. Down-regulation of TYRP2 expression or activity can be accomplished using a genetic therapy such as antisense therapy, or by using small molecules which regulate TYRP2. Excerpt(s): The present invention relates to the treatment of melanoma, and in particular to treatment and diagnosis of anti-cancer therapy resistance in melanoma, as well as to the evaluation of resistance of a tumor or melanoma cells to anticer therapy.... The
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tendency of tumors to express resistance to therapeutic agents remains a major obstacle in cancer treatment. Resistance mechanisms can be classified as either physiological or cellular (see Bradley et al. (1988) Biochim. Biophys. Acta 948:87-128). Physiological resistance mechanisms refer to properties of the tumor such as vascularity, that limit drug penetration into the rumor. Cellular resistance mechanisms involve the ability of individual cancer cells to undergo mutations or other types of genetic alterations which biochemically render these cells more resistant to the cytotoxic effects of anti-cancer therapeutic drugs. Such mechanisms include decreased drug uptake, increased drug efflux and increased drug detoxification. Resistant cancer cells may arise en masse in a de novo fashion prior to drug treatment ("intrinsic drug resistance") or they can be selected for by the drug ("acquired drug resistance"). One type of cancer which is well known for its intrinsic resistance to anti-ancer therapeutic drugs is malignant melanoma.... The incidence of malignant melanoma is increasing more rapidly than any other type of human cancer in North America (Armstrong et al. (1994) Cancer Surv. 1920:219-240). Although melanoma is a curable cancer, the primary tumor must be removed at a very early stage of disease progression, i.e., before it has spread to distant sites. The presence of micrometastases can, and often do, lead to eventual symptomatic metastases. Because melanomas are intrinsically resistant to conventional methods of either chemotherapy or radiotherapy, it is virtually impossible to effectively treat such lesions in a clinically meaningful manner. Web site: http://www.delphion.com/details?pn=US06573050__ •
Use of a melanoma differentiation associated gene (mda 7) for reversing a cancerous phenotype Inventor(s): Fisher; Paul B. (Scarsdale, NY) Assignee(s): The Trustees of Columbia University in the City of New York (New York, NY) Patent Number: 5,710,137 Date filed: August 16, 1996 Abstract: This invention provides a method for reversing the cancerous phenotype of a cancer cell by introducing a nucleic acid having the melanoma differentiation associated gene (mda-7) into the cell under conditions that permit the expression of the gene so as to thereby reverse the cancerous phenotype of the cell. This invention also provides a method for reversing the cancerous phenotype of a cancer cell by introducing the gene product of the above-described gene into the cancerous cell so as to thereby reverse the cancerous phenotype of the cell. This invention also provides a pharmaceutical composition having an amount of a nucleic acid having the melanoma differentiation associated gene (mda-7) or the gene product of a melanoma differentiation associated gene (mda-7) effective to reverse the cancerous phenotype of a cancer cell and a pharmaceutically acceptable carrier. Excerpt(s): The invention disclosed herein was made with Government support under NCI/NIH Grant No. CA35675 from the Department of Health and Human Services. Accordingly, the U.S. Government has certain rights in this invention.... Throughout this application, various references are referred to within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Full bibliographic citation for these references may be found at the end of this application, preceding the claims.... Cancer is a complex multifactor and multistep process involving
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the coordinated expression and suppression of genes functioning as positive and negative regulators of oncogenesis (1-5). Direct cloning strategies, based on transfer of a dominant transforming or tumorigenic phenotype, have identified positive acting oncogenes (6-9). In contrast, the detection and cloning of genes that suppress the cancer phenotype have proven more difficult and elusive (10-15). A direct approach for isolating genes directly involved in regulating growth and differentiation involves subtraction hybridization between cDNA libraries constructed from actively growing cancer cells and cDNA libraries from cancer cells induced to lose proliferative capacity irreversibly and terminally differentiate (13, 14). This experimental strategy has been applied to human melanoma cells, induced to terminally differentiate by treatment with recombinant human interferon.beta. (IFN-.beta.) and mezerein (MEZ), resulting in the cloning of novel melanoma differentiation-associated (mda) genes not previously described in DNA data bases (13, 14). A direct role for specific mda genes in mediating growth and cell cycle control is apparent by the identification and cloning of mda-6 (1316), which is identical to the ubiquitous inhibitor of cyclin-dependent kinases p21 (17). The importance of p21 in growth control is well documented and this gene has been independently isolated, as WAF-1, CIP-1, and SDI-1, by a number of laboratories using different approaches (18-20). These studies indicate that specific genes associated with proliferative control are induced and may contribute to the processes of growth arrest and terminal differentiation in human cancer cells. Web site: http://www.delphion.com/details?pn=US05710137__ •
Use of a melanoma differentiation associated gene (mda-7) for inducing apoptosis of a tumor cell Inventor(s): Fisher; Paul B. (Scarsdale, NY) Assignee(s): The Trustees of Columbia University in the City of New York (New York, NY) Patent Number: 6,355,622 Date filed: February 16, 1999 Abstract: This invention provides a method for reversing the cancerous phenotype of a cancer cell by introducing a nucleic acid having the melanoma differentiation associated gene (mda-7) into the cell under conditions that permit the expression of the gene so as to thereby reverse the cancerous phenotype of the cell. This invention also provides a method for reversing the cancerous phenotype of a cancer cell by introducing the gene product of the above-described gene into the cancerous cell so as to thereby reverse the cancerous phenotype of the cell. This invention also provides a pharmaceutical composition having an amount of a nucleic acid having the melanoma differentiation associated gene (mda-7) or the gene product of a melanoma differentiation associated gene (mda-7) effective to reverse the cancerous phenotype of a cancer cell and a pharmaceutically acceptable carrier. Excerpt(s): Throughout this application, various references are referred to within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Full bibliographic citation for these references may be found at the end of each series of experiments.... Cancer is a complex multifactor and multistep process involving the coordinated expression and suppression of genes functioning as positive and negative regulators of oncogenesis (1-5). Direct cloning strategies, based on transfer of a dominant transforming or tumorigenic phenotype, have identified positive
Patents 349
acting oncogenes (6-9). In contrast, the detection and cloning of genes that suppress the cancer phenotype have proven more difficult and elusive (10-15). A direct approach for isolating genes directly involved in regulating growth and differentiation involves subtraction hybridization between cDNA libraries constructed from actively growing cancer cells and cDNA libraries from cancer cells induced to lose proliferative capacity irreversibly and terminally differentiate (13,14). This experimental strategy has been applied to human melanoma cells, induced to terminally differentiate by treatment with recombinant human interferon.beta. (IFN-.beta.) and mezerein (MEZ), resulting in the cloning of novel melanoma differentiation-associated (mda) genes not previously described in DNA data bases (13,14). A direct role for specific mda genes in mediating growth and cell cycle control is apparent by the identification and cloning of mda-6 (1316), which is identical to the ubiquitous inhibitor of cyclin-dependent kinases p21 (17). The importance of p21 in growth control is well documented and this gene has been independently isolated, as WAF-1, CIP-1, and SDI-1, by a number of laboratories using different approaches (18-20). These studies indicate that specific genes associated with proliferative control are induced and may contribute to the processes of growth arrest and terminal differentiation in human cancer cells.... The mda-7 gene was cloned from a differentiation inducer (IFN-.beta. plus MEZ)-treated human melanoma (H0-1) subtracted library (13,14). The full-length mda-7 cDNA is 1718 nucleotides, and the major open reading frame encodes a novel protein of 206 aa with an M.sub.r of 23.8 kDa (21). Previous studies indicate that mda-7 is induced as a function of growth arrest and induction of terminal differentiation in human melanoma cells (14,21). mda-7 expression also inversely correlates with melanoma progression--i.e., actively growing normal human melanocytes express more mda-7 than metastatic human melanoma cells (21). Moreover, mda-7 is growth inhibitory toward human melanoma cells in transient transfection assays and in stable transformed cells containing a dexamethasone (DEX)inducible mda-7 gene (21). These studies indicate that mda-7 may contribute to the physiology of human melanocytes and melanomas, and this gene has growth suppressive properties when overexpressed in human melanoma cells. Web site: http://www.delphion.com/details?pn=US06355622__ •
Use of texaphyrins in detection of melanin and melanin metabolites diagnostic of melanotic melanoma Inventor(s): Woodburn; Kathryn W. (Sunnyvale, CA), Young; Stuart W. (Portola Valley, CA) Assignee(s): Pharmacyclics, Inc. (Sunnyvale, CA) Patent Number: 6,022,526 Date filed: July 30, 1997 Abstract: Melanotic melanoma tumor or cells, melanin, or melanin metabolites are detected, identified, and localized when bound to texaphyrins or texaphyrin metal complexes. The present invention provides texaphyrins and texaphyrin metal complexes as reagents for in vivo or in vitro detection for melanin or melanin metabolites predictive of the presence of melanotic melanoma. Excerpt(s): The present invention relates generally to the fields of cancer diagnosis, and particularly to methods for diagnosis of melanotic melanoma or metastatic melanotic melanoma. The use of texaphyrins for in vivo or in vitro detection of melanin or melanin metabolites diagnostic of melanotic melanoma is provided herein. A further aspect of the invention is a method of identifying, localizing, and diagnosing melanin-containing
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cells or tissues.... The incidence and mortality rates of malignant melanoma continue to rise dramatically throughout the world. In the United States, it is estimated that one in 90 Americans will develop melanoma by the year 2000. Melanoma is one of the most feared neoplasms because of the high mortality associated with metastatic involvement.... Malignant melanoma is commonly found in early stages in the form of a skin lesion. The lesion often results from the transformation of a preexisting nevus or discolored patch of skin containing aggregates of melanocytes. The best prognostic factor for determining the presence of metastatic disease is the depth of invasion of the primary lesion. Lesions with a depth greater than 0.8 mm have an increased risk for metastases. Melanomas usually metastasize first via the lymphatic system, with involvement of regional nodes, and then via blood vessels, with dissemination to subcutaneous tissue and to the liver, lungs, and brain. The presence of regional lymph node metastasis is predictive of a poor prognosis. Web site: http://www.delphion.com/details?pn=US06022526__ •
Vaccines against melanoma Inventor(s): Pennathur; Sridhar (Seattle, WA), Hu; Shiu-Lok (Redmond, WA), Purchio; Anthony (Seattle, WA), Hellstrom; Ingegerd (Seattle, WA), Rose; Timothy M. (Seattle, WA), Plowman; Gregory D. (Seattle, WA), Estin; Charles D. (Bainbridge Island, WA), Brown; Joseph P. (Seattle, WA), Hellstrom; Karl E. (Seattle, WA) Assignee(s): Oncogen (Seattle, WA) Patent Number: 5,141,742 Date filed: May 13, 1991 Abstract: Peptides or proteins related to a melanoma associated antigen are described. These are produced in large quantities via recombinant DNA techniques and/or by chemical synthetic methods. The peptides or proteins can be used as immunogens in vaccine formulations which can induce an immune response that selectively destroys melanoma cells in a vaccinated individual. Where the peptides or proteins are expressed by a recombinant virus, inactivated or live virus vaccine formulations may be prepared. Excerpt(s): The present invention is directed to vaccine formulations which can induce an immune response that selectively destroys melanoma cells in a vaccinated individual. Accordingly, a peptide or protein related to a melanoma associated antigen is produced in large quantities via recombinant DNA techniques and/or by chemical synthetic methods. The peptide or protein of the present invention can be used as an immonogen in a vaccine formulation. In certain embodiments where the peptide or protein related to a melanoma associated antigen is expressed by a recombinant virus, the recombinant virus itself may be used as an immunogen in a vaccine formulation. The invention also provides for processes which include the use of recombinant DNA techniques as well as chemical synthetic methods that enable the production of peptides or proteins related to the melanoma associated antigen in large quantities.... The invention is illustrated by way of example using as immunogens peptides related to p97, a monomeric cell surface sialoglycoprotein with an apparent molecular weight of slightly less than 97,000 daltons which is a cell surface component of melanoma cells.... Work with experimental animals, particularly rodents, has shown that most tumors induced by oncogenic viruses express antigens encoded by the viral genome, and that immunization with these antigens can lead to rejection of a subsequent challenge of tumor cells induced by the same virus. Although much of this work was done with laboratory strains of virus, such as SV40, polyoma virus, and Friend, Moloney, or Rauscher murine leukemia viruses, horizontal
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and vertical transmisison of oncogenic viruses in nature have been demonstrated; indeed a commercial vaccine against virus-induced feline leukemia and sarcoma is now available. Web site: http://www.delphion.com/details?pn=US05141742__
Patent Applications on Skin 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 skin cancer: •
Antisense inhibiting melanoma invasion and functional analogs thereof Inventor(s): Brodt, Pnina; (Montreal, CA), Durko, Margaret; (Cote St-Luc, CA) Correspondence: KLAUBER HACKENSACK; NJ; 07601
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JACKSON;
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Patent Application Number: 20030108530 Date filed: February 11, 2003 Abstract: The present invention relates to an antisense to inhibit melanoma invasion, to an expression vector and to a method for substantially inhibiting tumor cell invasion of an extracellular matrix (ECM) and other invasive processes such as angiogenesis, and particularly plasmin-mediated proteolysis thereof in a patient, by suppression of type I collagenase (MMP-1) expression in the patient. Excerpt(s): The present invention relates to an antisense to inhibit melanoma invasion, to an expression vector comprising same and to a method for substantially inhibiting tumor cell invasion of an extracellular matrix (ECM) and particularly plasmin-mediated proteolysis thereof in a patient, by suppressing expression or function of type I collagenase (MMP-1) in the patient.... The extracellular matrix (ECM) is a complex structure consisting mainly of basement membranes and interstitial stroma and composed of collagen, glycoproteins and proteoglycans, forming a dense meshwork normally impenetrable to migrating cells. ECM turnover is essential for normal physiological processes such as organogenesis and wound healing. In pathological processes requiring degradation of ECM such as cancer invasion and metastasis, the tight regulation of ECM turnover is disrupted, leading to increased ECM proteolysis. Several different classes of proteinases are known to participate in ECM degradation. These include matrix metalloproteinases (MMPs) such as type I (MMP-1) and type IV (MMP-2, MMP-9) collagenases and stromelysin-1 (MMP-3), and serine proteinases such as the urokinase-type plasminogen activator (uPA) and plasmin. These enzymes have all been implicated in cancer invasion and metastasis (Mignatti, P., and Rifkin, D. B. (1993) Physiol. Rev. 73, 161-195).... The uPA enzyme converts the zymogen plasminogen to its enzymatically active form plasmin. Plasmin in turn can initiate the conversion of the uPA zymogen (pro-uPA) to its active form uPA, resulting in an autocatalytic loop. Activation of plasminogen to plasmin occurs at the cell surface where uPA binds through a specific cell surface receptor (urokinase-type plasminogen activator receptor, or uPAR) and plasminogen binds through as yet unidentified binding sites. Receptor10
This has been a common practice outside the United States prior to December 2000.
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bound uPA can be inactivated by the plasminogen activator inhibitors PAI-1 and PAI-2. Binding of the ECM-associated inhibitor PAI-1 to the receptor-linked uPA in turn triggers the internalization of the whole complex and the reexpression of the receptor at new sites. This provides a mechanism for coordinated regulation of uPAR turnover, cell surface plasminogen activation and cellular migration (Mignatti, P., and Rifkin, D. B. (1993) Physiol. Rev. 73, 161-195). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Basal cell carcinoma tumor suppressor gene Inventor(s): Smyth, Ian McLeod; (Fig Tree Pocket, AU), Pressman, Carol Leah; (Houston, TX), Leffell, David J. (New Haven, CT), Gerrard, Bernard; (Frederick, MD), Goldstein, Alisa Miriam; (Rockville, MD), Toftgard, Rune Carl Magnus; (Skarholmen, SE), Negus, Kylie; (Queenslopes, AU), Wainwright, Brandon; (Bardon, AU), Bale, Allen E. (Northford, CT), Dean, Michael Carlton; (Frederick, MD), Gillies, Susan Alana; (Newfarm, AU), Chenevix-Trench, Georgia; (Toowong, AU), Hahn, Heidi Eve; (Goettingen, DE), Wicking, Carol; (Auchenflower, AU), Christiansen, Jeffrey; (Yeronga, AU), Gailani, Mae R. (Guilford, CT), Shanley, Susan Mary; (Norman Park, AU), Chidambaram, Abirami; (Frederick, MD), Vorechovsky, Igor; (Huddinge, SE), Holmberg-Lindstrom, Erika; (Taby, SE), Zaphiropoulos, Peter G. (Tullinge, SE), Unden, Anne Birgitte; (Djursholm, SE) Correspondence: TOWNSEND AND TOWNSEND AND CREW, LLP; TWO EMBARCADERO CENTER; EIGHTH FLOOR; SAN FRANCISCO; CA; 94111-3834; US Patent Application Number: 20030171566 Date filed: November 22, 2002 Abstract: This invention provides for a tumor suppressor gene inactivation of which is a causal factor in nevoid basal cell carcinoma syndrome and various sporadic basal cell carcinomas. The NBCCS gene is a homologue of the Drosophila patched (ptc) gene. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 60/017,906, filed on May 17, 1996 and U.S. application Ser. No: 60/019765, filed on Jun. 14, 1996, both of which are herein incorporated by reference for all purposes.... This invention pertains to the field of oncology. In particular, this invention pertains to the discovery of a tumor suppressor gene implicated in the etiology of nevoid basal cell carcinoma syndrome (NBCCS) and various cancers including basal cell carcinomas.... Many cancers are believed to result from a series of genetic alterations leading to progressive disordering of normal cellular growth mechanisms (Nowell (1976) Science 194:23, Foulds (1958) J. Chronic Dis. 8:2). In particular, the deletion or multiplication of copies of whole chromosomes or chromosomal segments, or specific regions of the genome are common (see, e.g., Smith et al. (1991) Breast Cancer Res. Treat. 18: Suppl. 1: 5-14; van de Vijer & Nusse (1991) Biochim. Biophlys. Acta. 1072: 33-50; Sato et al. (1990) Cancer. Res. 50: 7184-7189). In particular, the amplification and deletion of DNA sequences containing proto-oncogenes and tumor-suppressor genes, respectively, are frequently characteristic of tumorigenesis. Dutrillaux et al. (1990) Cancer Genet. Cytogenet. 49: 203-217. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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•
Compositions for treatment of melanoma and method of using same Inventor(s): Wolchok, Jedd D. (New York, NY), Houghton, Alan N. (New York, NY), Bergman, Philip J. (Tarrytown, NY) Correspondence: OPPEDAHL AND LARSON LLP; P O BOX 5068; DILLON; CO; 804355068; US Patent Application Number: 20020150589 Date filed: November 27, 2001 Abstract: Melanoma can be treated in a mammalian subject by administering to the subject an immunologically-effective amount of a xenogeneic melanoma-associated differentiation antigen. For example, genetic immunization with a plasmid containing a sequence encoding human gp75 has been shown to be effective in treatment of dogs with melanoma. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/627,694, filed Jul. 28, 2000, and of U.S. patent application Ser. No. 09/308,697 filed May 21, 1999 which is a.sctn.371 National Phase of International Application No. PCT/US97/22669. This application claims the benefit under 35 USC.sctn.119(e) of U.S. Provisional Applications Nos. 60/036,419 filed Feb. 18, 1997; 60/032,535 filed Dec. 10, 1996 and 60/180,651 filed Jan. 26, 2000. All of the above-mentioned applications are incorporated herein by reference.... This application relates to compositions for treatment of melanoma and to a method of using such compositions. The invention utilizes compositions containing xenogeneic differentiation antigens which are associated with melanoma to provide effective therapy.... Differentiation antigens are tissue-specific antigens that are shared by autologous and some allogeneic tumors of similar derivation, and on normal tissue counterparts at the same stage of differentiation. Differentiation antigens have been shown to be expressed by a variety of tumor types, including melanoma, leukemia, lymphomas, colorectal carcinoma, breast carcinoma, prostate carcinoma, ovarian carcinoma, pancreas carcinomas, and lung cancers. For example, differentiation antigens expressed by melanoma cells include Melan-A/MART-1, Pmel17, tyrosinase, and gp75. Differentiation antigen expressed by lymphomas and leukemia include CD19 and CD20/CD20 B lymphocyte differentiation markers). An example of a differentiation antigen expressed by colorectal carcinoma, breast carcinoma, pancreas carcinoma, prostate carcinoma, ovarian carcinoma, and lung carcinoma is the mucin polypeptide muc-1. A differentiation antigen expressed by breast carcinoma is her2/neu. The her2/neu differentiation antigen is also expressed by ovarian carcinoma. Differentiation antigens expressed by prostate carcinoma include prostate specific antigen, prostatic acid phosphatase, and prostate specific membrane antigen. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Detection of chromosome copy number changes to distinguish melanocytic nevi from malignant melanoma Inventor(s): Bastian, Boris; (San Francisco, CA), Pinkel, Daniel; (Walnut Creek, CA) Correspondence: TOWNSEND AND TOWNSEND AND CREW; TWO EMBARCADERO CENTER; EIGHTH FLOOR; SAN FRANCISCO; CA; 94111-3834; US Patent Application Number: 20010029021 Date filed: April 13, 2001
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Abstract: The present invention provides for methods of distinguishing melanocytic nevi, such as Spitz nevi, from malignant melanoma. The methods comprise contacting a nucleic acid sample from a patient with a probe which binds selectively to a target polynucleotide sequence on a chromosomal region such as 11p, which is usually amplified in Spitz nevi. The nucleic acid sample is typically from skin tumor cells located within a tumor lesion on the skin of the patient. Using another probe which binds selectively to a chromosomal region such as 1q, 6p, 7p, 9p, or 10q, which usually show altered copy number in melanoma, the method can determine that those tumor cells with no changes in copy number of 1q, 6p, 7p, 9p, or 10q, are not melanoma cells but rather Spitz nevus cells. The finding of amplifications of chromosome 11p would be an additional indication of Spitz nevus. Excerpt(s): The melanocyte can give rise to a plethora of morphologically different tumors. Most of them are biologically benign and are referred to as melanocytic nevi. Examples of melanocytic nevi are congenital nevi, Spitz nevi, dysplastic or Clark's nevi, blue nevi, lentigo simplex, and deep penetrating nevus. Pigmented spindle cell nevus is regarded as a subset of Spitz nevi.... Melanoma refers to malignant neoplasms of melanocytes. Its proper diagnosis and early treatment is of great importance because advanced melanoma has a poor prognosis, but most melanomas are curable if excised in their early stages. While clinicians make the initial diagnosis of pigmented lesions of the skin, pathologists make the final diagnosis. Although, in general the histopathological diagnosis of melanoma is straightforward, there is a subset of cases in that it is difficult to differentiate melanomas from benign neoplasm of melanocytes, which have many variants that share some features of melanomas (LeBoit, P. E. STIMULANTS OF MALIGNANT MELANOMA: A ROGUE'S GALLERY OF MELANOCYTIC AND NONMELANOCYTIC IMPOSTERS, In Malignant Melanoma and Melanocytic Neoplasms, P. E. Leboit, ed. (Philadelphia: Hanley & Belfus), pp. 195-258 (1994)). Even though the diagnostic criteria for separating the many simulators of melanoma are constantly refined, a subset of cases remains, where an unambiguous diagnosis cannot be reached (Farmer et al., DISCORDANCE IN THE HISTOPATHOLOGIC DIAGNOSIS OF MELANOMA AND MELANOCYTIC NEVI BETWEEN EXPERT PATHOLOGISTS, Human Pathol. 27: 528-31 (1996)). The most frequent and important diagnostic dilemma is the differential diagnosis between Spitz nevus, a neoplasm composed of large epithelioid or spindled melanocytes, and melanoma.... Misdiagnosis of Spitz nevus as melanoma and vice versa has been repeatedly reported in the literature (Goldes et al., Pediatr. Dermatol., 1: 295-8 (1984); Okun, M. R. Arch. Dermatol. 115: 1416-1420 (1979); Peters et al., Histopathology, 10, 1289-1302 (1986)). A retrospective study of 102 melanomas of childhood found that only 60 cases were classified as melanoma by a panel of experts, the majority of the remainder being classified as Spitz nevi (Spatz, S., Int. J. Cancer 68, 317-24 (1996)). The hazard of mistaking a Spitz nevus for melanoma can be severe and traumatic: The patients may be subjected to needless surgery, unable to plan for the future, and psychologically traumatized. For obvious reasons, the misdiagnosis of a melanoma as a benign nevus can have even more dramatic consequences. The presence of this diagnostic gray zone has even led the authors of a review article in the "Continuing Medical Education" section of the Journal of the American Association of Dermatology to conclude that Spitz nevus and melanoma may "actually exist on a continuum of disease" (Casso et al., J. Am. Acad. Dermatol., 27, 90113 (1992)). The authors recommended that "treatment include complete excision of al Spitz nevi followed by reexcision of positive margins if present." The need for improved diagnostics for melanocytic neoplasms has led to numerous attempts to improve diagnostic accuracy by the use of markers that could be detected by immunohistochemistry. While there have been prior efforts aimed at resolving this problem,
Patents 355
none have been satisfactory. For example, even though tests employing markers such as S100, HMB45 are useful in establishing that a poorly differentiated tumor is of melanocytic lineage, adjunctive techniques have been of little help in separating benign from malignant melanocytic lesions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Detection of melanoma Inventor(s): Pinkel, Daniel; (Walnut Creek, CA), Bastian, Boris; (San Francisco, CA) Correspondence: TOWNSEND AND TOWNSEND AND CREW, LLP; TWO EMBARCADERO CENTER; EIGHTH FLOOR; SAN FRANCISCO; CA; 94111-3834; US Patent Application Number: 20030073119 Date filed: September 9, 2002 Abstract: The present invention provides methods of screening for the presence of premalignant melanocytes in a sample from a patient. The methods comprise contacting a nucleic acid sample from a biological sample from the patient with a probe which binds selectively to a target polynucleotide sequence on a chromosomal region which is amplified in melanoma cells. Excerpt(s): Melanoma refers to malignant neoplasms of melanocytes. Its proper diagnosis and early treatment by complete excision is of great importance because advanced melanoma has a poor prognosis and most melanomas are curable if excised in their early stages. In most instances the transformed melanocytes produce increased amounts of pigment so that the area involved can easily be seen by the clinician. When the excision margins of a melanoma are identified based on this macroscopic appearance and no margin of seemingly uninvolved skin is excised, melanoma has the risk of local recurrence.... This has led to the recommendation to remove a safety margin of normal skin that varies from 0.5 to 3 cm depending on the thickness of the primary tumor (Wingo, P. A. et al., Cancer 82:1197-207 (1998); Rigel, D. S. et al., J Am Acad Dermatol 34:839-47 (1996); McGovern, V. J. et al., Cancer 32:1446-57 (1973)). It is obvious that the resulting defect inflicted by the excision can be considerable. If a melanoma measuring 2 cm in diameter that has a thickness of >4 mm is to be excised under the current guidelines, the resulting defect would be 8 cm (2+3+3 cm) in diameter. The closure of excisions with 2-3 cm margins usually require skin grafting and have the potential of adverse consequences such as unsatisfactory cosmetic result, increased morbidity and costs, and sometimes permanent functional impairment. Even with "adequate" safety margins, the melanoma can recur locally.... Obviously, it would be desirable if the margins could be tailored to the needs of the individual patient's tumor. Unfortunately, so far, no technique exists that is able to detect the extent of a tumor accurately. In some types of melanomas the horizontally expanding portion of the tumor mainly consists of single melanocytes along the basal layer of the epidermis. These melanoma types are referred to as lentiginous melanomas. In these, the amount of atypical cells often gradually diminishes towards the margins so that it can be difficult or impossible for the pathologist to determine the border of the melanoma. However, current thinking implies that in most instances, the extent of a melanoma can be assessed by pathology. The fact that the removal of a margin of "healthy" skin reduces the recurrence rate, however, suggests that this skin is actually not healthy but contains residual melanoma which is undetectable by current methods. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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•
Immunogenic targets for melanoma Inventor(s): Barber, Brian; (White Plains, NY), Karunakaran, Liza; (Thornhill, CA), Emtage, Peter; (Sunnyvale, CA), Pedyczak, Artur; (Pickering, CA) Correspondence: Patrick Halloran; Aventis Pasteur; One Discovery Drive; Swiftwater; PA; 18370; US Patent Application Number: 20030113919 Date filed: August 15, 2002 Abstract: The present invention relates to peptides, polypeptides, and nucleic acids and the use of the peptide, polypeptide or nucleic acid in preventing and/or treating cancer. In particular, the invention relates to peptides and nucleic acid sequences encoding such peptides for use in diagnosing, treating, or preventing melanoma. Excerpt(s): This application claims priority to U.S. Ser. No. 60/313,438 filed Aug. 17, 2003; No. 60/313,572 filed Aug. 17, 2001; No. 60/313,573 filed Aug. 17, 2001; No. 60/313,572 filed Aug. 17, 2001; and, No. 60/313,574 filed Aug. 17, 2001.... The present invention relates to peptides, polypeptides, and nucleic acids and the use of the peptide, polypeptide or nucleic acid in preventing and/or treating cancer. In particular, the invention relates to peptides and nucleic acid sequences encoding such peptides for use in diagnosing, treating, or preventing melanoma.... There has been tremendous increase in last few years in the development of cancer vaccines with tumour-associated antigens (TAAs) due to the great advances in identification of molecules based on the expression profiling on primary tumours and normal cells with the help of several techniques such as high density microarray, SEREX, immunohistochemistry (IHC), RT-PCR, in-situ hybridization (ISH) and laser capture microscopy (Rosenberg, Immunity, 1999; Sgroi et al, 1999, Schena et al, 1995, Offringa et al, 2000). The TAAs are antigens expressed or over-expressed by tumour cells and could be specific to one or several tumours for example CEA antigen is expressed in colorectal, breast and lung cancers. Sgroi et al (1999) identified several genes differentially expressed in invasive and metastatic carcinoma cells with combined use of laser capture microdissection and cDNA microarrays. Several delivery systems like DNA or viruses could be used for therapeutic vaccination against human cancers (Bonnet et al, 2000) and can elicit immune responses and also break immune tolerance against TAAs. Tumour cells can be rendered more immunogenic by inserting transgenes encoding T cell co-stimulatory molecules such as B7.1 or cytokines such as IFN-.gamma., IL2, or GM-CSF, among others. Co-expression of a TAA and a cytokine or a co-stimulatory molecule can develop effective therapeutic vaccine (Hodge et al, 95, Bronte et al, 1995, Chamberlain et al, 1996). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Inhibition of mitogen-activated protein kinase (MAPK) pathway: a selective therapeutic strategy against melanoma Inventor(s): Koo, Han-Mo; (Kentwood, MI), Vande Woude, George F. (Ada, MI) Correspondence: VENABLE, BAETJER, HOWARD AND CIVILETTI, LLP; P.O. BOX 34385; WASHINGTON; DC; 20043-9998; US Patent Application Number: 20020054869 Date filed: August 31, 2001
Patents 357
Abstract: Inhibitors of the MAPK pathway, including MEK-directed proteases and small molecule inhibitors, are cytotoxic to human melanoma cells in vitro and in vivo via apoptotic mechanisms. These compounds are used to kill melanoma cells and to treat subjects with melanoma, either alone or in combination with other therapeutic modalities. Excerpt(s): The invention in the field of biochemistry and medicine relates to methods to kill melanoma cells and treat melanoma tumors in a selective manner using compositions that inhibit the mitogen-activated protein kinase (MAPK) pathway.... The MAPK pathways are found in, and highly conserved among, all eukaryotes. These pathways play an integral role in the transduction of various extracellular signals into the nucleus. The best-characterized mammalian pathway, designated Raf-MEK1/2ERK1/2, includes the MAPK enzymes also known as ERK1 and ERK2, which are phosphorylated and activated by the dual-specificity kinases that have been termed "MAPK/ERK kinases" (abbreviated variously as MAPKK1 and MAPKK2 or, as will be used herein, MEK1 and MEK2). The MEK enzymes are in turn phosphorylated and activated by the Raf kinases (Lewis, TS. et al., Adv Canc Res, 74:49-139 (1998)).... The MAPK pathway is involved in the regulation of cell growth, survival, and differentiation (Lewis et al., supra). Furthermore, activated MAPK and/or elevated level of MAPK expression have been detected in a variety of human tumors (Hoshino, R. et al., Oncogene 18:813-822 (1999); Salh, B et al., Anticancer Res. 19:741-48 (1999); Sivaraman, V S et al., J. Clin. Invest. 99:1478-483 (1997); Mandell, J W et al., Am. J. Pathol. 153:1411-23 (1998); Licato, L. L. et al. Digestive Diseases and Sciences 43, 14541464 (1998)) and may be associated with invasive, metastatic and angiogenic activities of tumor cells. Thus, inappropriate activation of the MAPK pathway is an essential feature common to many types of tumors. For this reason, participants in this signaling pathway, such as MEK, are potential targets for cancer therapy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Melanoma and prostate cancer specific antibodies for immunodetection and immunotherapy Inventor(s): Vielkind, Juergen R. (Vancouver, CA) Correspondence: SCULLY, SCOTT, MURPHY & PRESSER; 400 Garden City Plaza; Garden City; NY; 11530; US Patent Application Number: 20020055121 Date filed: April 19, 2001 Abstract: Methods and compositions are provided for detecting antigens having a specific epitope associated with melanoma and prostatic carcinoma. The epitope is present in melanoma cells and prostatic cancer cells but is essentially absent from melanocytes and normal prostatic tissue. The antibody can be used in diagnostic methods for histochemical detection of human melanoma and prostate carcinoma, of various progression stages and in treatment of melanoma and prostate carcinoma. Excerpt(s): The subject invention is related to the use of antibodies, which bind to a unique peptide obtainable from a Xiphophorus melanoma mrk-receptor tyrosine kinase for the diagnosis and therapy of melanoma and prostate cancer.... The ability to detect and diagnose cancer through the identification of tumor markers is an area of widespread interest. Tumor markers are substances, typically proteins, glycoproteins, polysaccharides, and the like which are produced by tumor cells and are characteristic
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thereof. Often, a tumor marker is produced by normal cells as well as by tumor cells. In the tumor cells, however, the production is in some way atypical. For example, production of a tumor marker may be greatly increased in the cancer cell. Additionally, the tumor marker may be released or shed into the circulation. Detection of such secreted substances in serum may be diagnostic of the malignancy. Therefore, it is desirable to identify previously unrecognized tumor markers, particularly, tumor markers which are secreted into the circulation and which may be identified by serum assays It is also desirable to develop methods and compositions which allow determination of the cellular origin of a particular tumor or other proliferative disease, for example by radioimaging techniques The location of the tumor markers on the surface of the cells, particularly where there is an extracellular domain that is accessible to antibodies (i.e., the domain acts as a receptor for the antibodies), provides a basis for targeting cytotoxic compositions to the receptor. Examples of compositions of interest in such a method include complement fixing antibodies or immunotoxins which bind to the receptor as a means of specifically killing those cells which express the receptor on the cell surface.... Human malignant melanoma arises from a series of stages starting with the harmless mole, going through intermediate stages of radial to invasive growth and ending in the destructive final stage of metastatic melanoma. Melanoma usually resists chemotherapy as well as radiotherapy. Surgery is the most effective treatment. However, for it to be effective, surgery requires early diagnosis which is unfortunately hampered by the lack of accurate markers for melanoma. Melanoma associated antigens have been found, but they are of little diagnostic value. For example, the nerve growth factor receptor is found in high density on melanoma cells. However, monoclonal antinerve growth receptor antibodies are specific for neural crest cell diseases rather than for melanoma alone. Likewise, other melanoma associated antigens against which antibodies have been raised are nonspecific for melanoma cells. Examples are the monoclonal antibodies raised against in vitro grown melanoma cells which are directed against gangliosides or glycoproteins present on the melanoma cells. Both antigens are also found on other cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Melanoma antigens and their use in diagnostic and therapeutic methods Inventor(s): Rosenberg, Steven A. (Potomac, MD), Kawakami, Yutaka; (Rockville, MD) Correspondence: LEYDIG VOIT & MAYER, LTD; TWO PRUDENTIAL PLAZA, SUITE 4900; 180 NORTH STETSON AVENUE; CHICAGO; IL; 60601-6780; US Patent Application Number: 20030144482 Date filed: July 3, 2001 Abstract: The present invention provides a nucleic acid sequence encoding a melanoma antigen recognized by T lymphocytes, designated MART-1. This invention further relates to bioassays using the nucleic acid sequence, protein or antibodies of this invention to diagnose, assess or prognoses a mammal afflicted with melanoma or metastata melanoma. This invention also provides immunogenic peptides derived from the MART-1 melanoma antigen and a second melanoma antigen designated gp100. This invention further provides immunogenic peptides derived from the MART-1 melanoma antigen or gp100 antigen which have been modified to enhance their immunogenicity. The proteins and peptides provided can serve as an immunogen or vaccine to prevent or treat melanoma.
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Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 08/231,565 filed on Apr. 22, 1994, which is herein incorporated by reference in its entirety.... This invention is in the field of prevention and treatment of human cancers. More specifically, this invention relates to genes encoding melanoma antigens recognized by T-Cells and their corresponding proteins and to preventative, diagnostic and therapeutic applications which employ these genes or proteins.... Melanomas are aggressive, frequently metastatic tumors derived from either melanocytes or melanocyte related nevus cells ("Cellular and Molecular Immunology" (1991) (eds) Abbas A. K., Lechtman, A. H., Pober, J. S. W. B. Saunders Company, Philadelphia: pages 340-341). Melanomas make up approximately three percent of all skin cancers and the worldwide increase in melanoma is unsurpassed by any other neoplasm with the exception of lung cancer in women ("Cellular and Molecular Immunology" (1991) (eds) Abbas, A. K., Lechtiman, A. H., Pober, J. S. W. B. Saunders Company Philadelphia pages: 340-342; Kirkwood and Agarwala (1993) Principles and Practice of Oncology 7:1-16). Even when melanoma is apparently localized to the skin, up to 30% of the patients will develop systemic metastasis and the majority will die (Kirkwood and Agarwala (1993) Principles and Practice of Oncology 7:1-16). Classic modalities of treating melanoma include surgery, radiation and chemotherapy. In the past decade immunotherapy and gene therapy have emerged as new and promising methods for treating melanoma. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Melanoma differentiation associated gene - 5 and promoter and uses thereof Inventor(s): Kang, Dong-Chul; (Rutherford, NJ), Fisher, Paul B. (Scarsdale, NY), Gopalkrishnan, Rahul V. (New York, NY) Correspondence: BAKER & BOTTS; 30 ROCKEFELLER PLAZA; NEW YORK; NY; 10112 Patent Application Number: 20030092043 Date filed: August 26, 2002 Abstract: The invention provides for an isolated nucleic acid encoding Mda-5 (melanoma differentiation associated gene-5) and an isolated Mda-5 polypeptide. The invention further provides a vector comprising the nucleic acid encoding Mda-5, as well as a host cell comprising the vector. The invention provides an antibody which specifically binds to an Mda-5 polypeptide. The invention further provides a method for determining whether a compound is an inducer of Mda-5 gene expression and assays to determine whether a compound modifies the enzymatic activity of the Mda-5 polypeptide. Excerpt(s): This application is a continuation of U.S. Ser. No. 09/515,363, filed Feb. 29, 2000, the contents of which are hereby incorporated by reference.... Throughout this application, various publications are referenced by author and date within the text. Full citations for these publications may be found listed alphabetically at the end of the specification immediately preceding the claims. All patents, patent applications and publications cited herein, whether supra or infra, are hereby incorporated by reference in their entirety. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein.... Abnormalities in differentiation are common occurrences in human cancers ((1)Fisher and Grant, 1985; (2) Waxman, 1995). Moreover, as cancer cells evolve, ultimately developing new phenotypes or acquiring a further elaboration of preexisting
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transformation-related properties, the degree of expression of differentiation-associated traits often undergo a further decline. These observations have been exploited as a novel means of cancer therapy in which tumor cells are treated with agents that induce differentiation and a loss of cancerous properties, a strategy called `differentiation therapy` ((2-4) Waxman et al., 1988, 1991; Jiang et al., 1994; Waxman, 1995). In principle, differentiation therapy may prove less toxic than currently employed chemotherapeutic approaches, including radiation and treatment with toxic chemicals. The ability to develop rational schemes for applying differentiation therapy clinically require appropriate in vitro and in vivo model systems for identifying and characterizing the appropriate agent or agents that can modulate differentiation in cancer cells without causing undue toxicity to normal cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Melanoma risk detection Inventor(s): Bergman, Wilma; (Oegstgeest, NL), Frants, Rune R. (Hoofddorp, NL), Martin, Nicholas G. (Queensland, AU), Sturm, Richard A. (Queensland, AU), Hayward, Nicholas K. (Queensland, AU), Duffy, David L. (Stafford, AU), Box, Neil F. (Queensland, AU), Van Der Velden, Pieter A. (Leiden, NL), Gruis, Nelleke A. (Leiderdorp, NL) Correspondence: AKIN GUMP STRAUSS HAUER & FELD L.L.P. ONE COMMERCE SQUARE; 2005 MARKET STREET, SUITE 2200; PHILADELPHIA; PA; 19103-7013; US Patent Application Number: 20030175721 Date filed: March 28, 2002 Abstract: A method of determining predisposition to melanoma is provided in the form of a molecular diagnostic method that detects the presence of a cyclin dependent kinase inhibitor 2A mutant allele and/or a melanocortin-1 receptor variant allele. The presence of a cyclin dependent kinase inhibitor 2A mutant allele increases the probability that an individual carrying a melanocortin-1 receptor variant allele will develop melanoma. Similarly, the presence of a melanocortin-1 receptor variant allele increases the probability that an individual carrying a cyclin dependent kinase inhibitor 2A mutant allele will develop melanoma. Excerpt(s): This application is entitled to priority pursuant to 35 U.S.C..sctn. 119(e) to U.S. provisional patent application 60/279,515, which was filed on Mar. 28, 2001.... Germline mutations in three different genes have been shown to influence risk of melanoma, specifically those encoding: cyclin dependent kinase inhibitor 2A (CDKN2A) (Hussussian et al. 1994; Kamb et al. 1994a), cyclin dependent kinase 4 (CDK4) (Zuo et al. 1996; Soufir et al. 1998) and the melanocortin-1 receptor (MC1R) (Palmer et al. 2000). The basis of melanoma risk as determined by these genes probably revolves around at least two independent pathways (Whiteman et al. 1998), one being the CDKN2A/CDK4 cell cycle and tumor suppressor gene axis, and the other a pigmentary mediated predisposition axis implicated by the recent association of MC1R variants with red hair, fair skin, freckling and melanoma (Palmer et al. 2000). Melanoma risk attributable to MC1R may arise through the action of solar UV-light on lighter skin tones with diminished tanning capacity (Bliss et al. 1995; Breitbart et al. 1997) or possibly through a more direct intrinsic effect on melanocytic cellular transformation. On the other hand, linkage of a quantitative trail locus (QTL) accounting for 33% of variance in flat mole count to the 9p21-22 region containing CDKN2A (Zhu et al. 1999) suggests that CDKN2A mutation may play a role in determination of mole density which in turn
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predisposes to later melanoma formation; this appears to be a risk factor quite distinct from the red hair and fair skin associated with MC1R variants (Garbe et al. 1994; Bliss et al. 1995; Grange et al. 1995; Grulich et al. 1996).... The p16.sup.INK4A protein encoded by the CDKN2A locus (Kamb et al. 1994b; Nobori et al. 1994) acts as a tumor suppressor that induces G1 cell cycle arrest through binding to and inhibiting the kinase activities associated with cyclin D complexes with both cyclin-dependent kinase 4 and 6 (CDK4 and CDK6). G1-S phase transition is usually dependent upon phosphorylation of the retinoblastoma protein (pRB) by the cyclinD1/CDK4 complex (Serrano et al. 1993; Lukas et al. 1995). Inactivation of CDKN2A via one of several mechanisms (homozygous deletion, mutation and/or promoter methylation) is a frequent event in tumors of many types (e.g. Kamb et al. 1994b; Nobori et al. 1994; reviewed by Ruas and Peters 1998). Furthermore, presence of mutations of this locus in the germline of a small proportion of familial melanoma patients (e.g. Hussussian et al. 1994; Kamb et al. 1994a; reviewed by Hayward 1998) indicates that p16 inactivation is an early and possibly initiating step in melanoma tumorigenesis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Melanoma therapy Inventor(s): Rose, Esther Helen; (Westfield, NJ), Rybak, Mary Ellen; (Waren, NJ) Correspondence: SCHERING-PLOUGH CORPORATION; PATENT DEPARTMENT (K6-1, 1990); 2000 GALLOPING HILL ROAD; KENILWORTH; NJ; 07033-0530; US Patent Application Number: 20010038833 Date filed: July 12, 2001 Abstract: Methods for treating treatment-naive as well as treatment-experienced patients having melanoma to increase the progression-free survival time involving administering a therapeutically effective amount of pegylated interferon-alpha, e.g., preferably pegylated interferon alpha-2b, as adjuvant therapy to definitive surgery are disclosed. Excerpt(s): This application claims the benefit of U.S. provisional patent application Ser. No. 60/128,308 filed Apr. 8, 1999.... Throughout this disclosure, various publications, patents and patent applications are referenced. The disclosures of these publications, patents and patent applications are herein incorporated by reference.... This invention relates to an improved therapy for treating patients having melanoma after definitive surgical removal of the lesions by administering a therapeutically effective dose of pegylated interferon-alpha for a time sufficient to increase progression-free survival time. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method and composition for selectively inhibiting melanoma Inventor(s): Kim, Darrick S.H.L. (Chicago, IL), DasGupta, Tapas K. (River Forest, IL), Pezzuto, John M. (River Forest, IL) Correspondence: MARSHALL, GERSTEIN & BORUN; 6300 SEARS TOWER; 233 SOUTH WACKER; CHICAGO; IL; 60606-6357; US Patent Application Number: 20030181429 Date filed: December 12, 2002
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Abstract: A composition and method of preventing or inhibiting tumor growth, and of treating malignant melanoma, without toxic side effects are disclosed. Betulinic acid or a betulinic acid derivative is the active compound of the composition, which is topically applied to the situs of tumor. Excerpt(s): This is a continuation-in-part application of U.S. patent application Ser. No. 08/407,756, filed on Mar. 21, 1995, now U.S. Pat. No. ______.... This invention relates to compositions and methods of selectively inhibiting tumors and, more particularly, to treating a malignant melanoma using plant-derived compounds and derivatives thereof.... Over the past four decades the incidence of melanoma has been increasing at a higher rate than any other type of cancer. It is now theorized that one in 90 American Caucasians will develop malignant melanoma in their lifetime. While an increasing proportion of melanomas are diagnosed sufficiently early to respond to surgical treatment and achieve a greater than 90% ten-year survival rate, it is estimated that nearly 7,000 individuals suffering from metastatic melanoma will die in the United States this year. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method and device for skin cancer screening Inventor(s): Kenet, Robert; (New York, NY) Correspondence: DAVIDSON, DAVIDSON & KAPPEL, LLC; 14th Floor; 485 Seventh Avenue; New York; NY; 10018; US Patent Application Number: 20030166993 Date filed: February 14, 2001 Abstract: A method for providing a preliminary diagnosis of skin cancer, more specifically a screening risk assessment of pigmented lesions receiving digital photographs of skin abnormalities from a plurality of consumers at a server, receiving medical information related to each of the plurality of consumers at the server, assigning an identification to at least one of the consumers and the digital photographs, reviewing the digital photographs and categorizing the digital photographs into at least three categories so as to define category information, the at least three categories including a first category of a first risk, a second category of risk lower than the first category and a third category of insufficient photograph quality, and providing the category information as a function of the identification. The digital photographs may be of pigmented skin lesions and may be clinical photographs or may utilize the optical technique of epiluminescence microscopy (ELM) to visualize pigmented or capillary structure below the skin surface that are not visible to the naked eye. Excerpt(s): The present application claims priority from U.S. Provisional Application No. 60/183,551 filed Feb. 18, 2000, the entire contents of which are hereby incorporated by reference herein.... The present invention relates generally to dermatology and more particularly to a method and device for aiding in screening populations of patients for skin cancer.... Skin cancer, the most deadly form of which is melanoma, typically is diagnosed by a dermatologist examining pigmented skin lesions (colloquially known as "moles") and/or other skin abnormalities on a patient. Typically, a dermatologist makes a determination based on visual inspection of each skin lesion's morphology, whether it is likely to be skin cancer or a potential precursor of skin cancer. This determination is made in the context of a patient's clinical history, risk factors for skin cancer, and other
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information. The dermatologist then decides if a pigmented lesion should the excised for histopathological evaluation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for detection of melanoma Inventor(s): Vogt, Thomas; (Pentling-Grossberg, DE) Correspondence: GARY CARY WARE & FRIENDENRICH LLP; 4365 EXECUTIVE DRIVE; SUITE 1600; SAN DIEGO; CA; 92121-2189; US Patent Application Number: 20030108896 Date filed: June 27, 2002 Abstract: The present invention provides non-invasive methods for detecting, monitoring, staging, and diagnosing malignant melanoma in a skin sample of a subject. The methods include analyzing expression in skin sample of one or more melanoma skin markers. The melanoma skin markers include IL-1 RI, endothelin-2, ephrin-A5, IGF Binding Protein 7, HLA-A0202 heavy chain, Activin A (.beta.A subunit), TNF RII, SPC4, and CNTF R.alpha.. The skin sample can include nucleic acids, and can be a human skin sample from a lesion suspected of being melanoma. Excerpt(s): This application claims priority under 35 U.S.C..sctn. 119(e) to Provisional Application Serial No. 60/302,348, filed Jun. 28, 2001, which is incorporated herein by reference in its entirety.... This invention relates to methods related to melanoma patient for detecting expression of genes in a skin sample of the epidermis related to malignant melanoma.... Malignant melanoma ranks second among adult cancers (behind adult leukemia) in potential years of life lost. Each year, over 47,000 new cases are diagnosed, and the incidence of cutaneous melanoma appears to be rising rapidly. Treatment of malignant melanoma involves surgical excision of the primary lesion, and vigilant monitoring to detect recurrence. Currently, there is no approved therapy for patients having intermediate risk of relapse. High-dose interferon, which can have serious side effects, is approved for treatment of patients having high-risk melanoma. There is no cure at this time for patients in whom metastasis to distant sites has occurred. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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METHOD FOR TREATING MELANOMA Inventor(s): HIRSCHMAN, SHALOM Z. (RIVERDALE, NY) Correspondence: MYRON COHEN; COHEN PONTANI LIEBERMAN & PAVANE; 551 FIFTH AVENUE SUITE 1210; NEW YORK; NY; 10176 Patent Application Number: 20020107184 Date filed: November 4, 1997 Abstract: The present invention discloses a method for treating patients having melanoma or melanoma associated symptoms by parenterally administering Product R, a peptide-nucleic acid preparation. Excerpt(s): The present invention relates to a method for using Product R as hereinafter defined to treat patients having melanoma.... Human melanoma, a malignant melanocytic tumor arising in a pigmented area: skin, mucous membranes, eyes, and
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CNS, represents the principal cause of death in patients with skin cancer in the United States and Europe. Malignant melanomas vary in size, shape, and color and in their propensity to invade and metastasize. About 40 to 50% of malignant melanomas develop from pigmented moles. Malignant transformation of pigmented moles may result from changes in size or color, especially spread of red, white, and blue pigmentation to surrounding normal skin; changes in surface characteristics, consistency or shape; or signs of inflammation in surrounding skin.... Melanoma includes four major types: lentigo-maligna melanoma which appears on the face or other sun-exposed areas in elderly patients as an asymptomatic, large, flat, tan or brown macule with darker brown or black spots scattered irregularly on its surface; superficial spreading melanoma which is usually asymptomatic and occurs most commonly on women's legs and men's torsos as a plaque with raised, indurated edges, and often shows red, white, and blue spots or small, sometimes protuberant, blue-black nodules; nodular melanoma which may occur anywhere on the body and is seen as dark, protuberant papules or a plaque that varies in color from pearl to gray to black; acroletiginous melanoma which is uncommon and arises on palmar, plantar, and subungual skin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods and materials for the diagnosis and treatment of sporadic basal cell carcinoma Inventor(s): Altaba, Ariel Ruiz i; (New York, NY) Correspondence: KLAUBER & JACKSON; 411 HACKENSACK AVENUE; HACKENSACK; NJ; 07601 Patent Application Number: 20030100032 Date filed: April 3, 2001 Abstract: Methods for detection of the onset or presence of sporadic basal cell carcinoma in an animal by measuring for elevated levels of extopic expression of Gli1 in the animal's epidermal tissue sample suspected of harboring sporadic basal cell carcinoma. Excerpt(s): The present invention relates generally to the diagnosis and treatment of pathologies involving tumor formation and neoplasia, and more particularly to the detection of a condition of skin cancer known as sporadic basal cell carcinoma (BCC), and to the identification of relevant therapeutic agents based on their effect on the level of expression and/or activity of the gene Gli1, as well as to the preparation of therapeutic compositions and methods of use.... Inductive signaling plays a critical role in both normal and disease development as developmental pathways that become unregulated in the adult can lead to abnormal patterning, overproliferation and neoplasia. One signaling pathway that is involved in several patterning events during embryogenesis is that triggered by secreted sonic hedgehog (Shh.sup.1-4). Shh binding to the membrane patched (ptc)-smoothened (smo) receptor complex elicits a cascade of cytoplasmic signal transduction events, including the inhibition of protein kinase A (PKA.sup.5-12) that leads to the transcription of the zinc finger transcription factor gene Gli1.sup.11,13. Gli1 is a proto-oncogene first isolated as an amplified gene in a glioma.sup.14 that can transform fibroblasts in cooperation with EIA.sup.15. Gli1 is a member of a family comprising two other related genes: Gli2 and Gli3.sup.16,17. However, only Gli1 has been shown to be a target of Shh and mimic its effects.sup.13. In Drosophila, hedgehog signaling.sup.18 similarly leads to the action of cubitus interruptus (ci), a Gli homolog that activates transcription of hedgehog-target
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genes.sup.19-23.... One of the processes in which Shh signaling is involved is the differentiation of ventral neural tube cell types acting as a notochord and floor platederived signal.sup.1,4,24-27. Previous work by the applicants herein on the role of sonic hedgehog signaling during neural plate patterning in frog (Xenopus laevis) embryos demonstrated that cells becoming floor plate respond to Shh by expressing Gli1, Pintallavis and HNF-3.beta., critical transcription factors that themselves can induce the differentiation of floor plate cells.sup.13,25,28,29. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods for inhibition of tumorigenic properties of melanoma cells Inventor(s): Satyamoorthy, Kapaettu; (Swarthmore, PA), Herlyn, Meenhard; (Wynnewood, PA) Correspondence: Licata & Tyrrell P.C. 66 E. Main Street; Marlton; NJ; 08053; US Patent Application Number: 20020165188 Date filed: January 30, 2002 Abstract: The present invention provides a method for preventing proliferation of melanoma cells by contacting melanoma cells with an agent which is capable of modulating the expression of E-cadherin in the melanoma cells thereby restoring keratinocyte control over melanoma cell proliferation. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 09/686,257 filed Oct. 11, 2000 which claims the benefit of priority of U.S. Ser. No. 60/159,353 filed Oct. 14, 1999.... Melanoma is a relatively common cancer. The incidence of cutaneous melanoma has risen rapidly in the last several decades (Parker et al., 1997, C A Cancer J. Clin 47:5-27; Ries et al., 2000, Cancer, 88:2398-424). Melanoma is notorious for its propensity to metastasize and its poor response to current therapeutic regimens. The transition from benign lesions to invasive, metastatic cancer occurs through a complex process involving changes in expression and function of oncogenes or tumor suppressor genes (Meier et al., 1998, Am. J. Pathol. 156:193-200).... In the human epidermis, melanocytes residing at the basement membrane are interspersed among basal keratinocytes. E-cadherin is physiologically expressed on the cell surface of keratinocytes and melanocytes, and is the major adhesion molecule (Hsu et al., 1996, J. Investig. Dermatol. Symp. Proc. 1:188-94; Tang et al., 1994, J. Cell Sci. 107:983-92). A progressive loss of E-cadherin expression occurs during melanoma development (Danen et al., 1996, Melanoma Res., 6:127-31; Hsu et al., 1996, J. Investig. Dermatolo Symp. Proc. 1:188-94; Scott & Cassidy, J. Invest Dermatol., 1998, 111:243-50; Silye et al., 1998, J. Pathol. 186:350-55). Under natural conditions, melanocytes express E-cadherin on their surface but melanoma cells do not (Hsu et al., 1994, J. Invest. Dermatol. Symp. Proc. 1:188-194). Additionally, melanoma cells express N-cadherin, while melanocytes do not. Melanoma cells express greater amounts of Mel-CAM and.alpha..sub.v.beta..sub.3 than do melanocytes. However, both cell types express.alpha.-catenin,.beta.-catenin and plakoglobin (Ozawa et al., J. Cell Biol., 1992, 116:989-996; Knudsen et al., 1995, J. Cell Biol. 130:67-77). Growth, proliferation, dendricity and cell-surface molecule composition of melanocytes are normally under the control of basal layer-type keratinocytes (Herlyn et al., 1987, Cancer Res. 47:3057-3061; Valyi-Nagy et al., 1993, Lab. Invest 69:152-159,; Shih et al., Am. J. Of Pathol., 1994, 145:837-845). Melanoma cells are refractory to the regulatory controls normally exerted by keratinocytes and therefore proliferate in an uncontrolled manner. Isolated and cultured melanocytes lose their normal phenotype,
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but regain it upon co-culture with basal layer type keratinocytes. The homeostatic effects of basal layer-type keratinocytes exert these effects upon melanocytes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Monoclonal antibody 1A7 and use for the treatment of melanoma and small cell carcinoma Inventor(s): Foon, Kenneth A. (Fremont, CA), Chatterjee, Sunil K. (Fort Wright, KY), Chatterjee, Malaya; (Fort Wright, KY) Correspondence: Catherine M. Polizzi; Morrison & Foerster LLP; 755 Page Mill Road; Palo Alto; CA; 94304-1018; US Patent Application Number: 20030114398 Date filed: May 21, 2002 Abstract: The present invention relates to monoclonal antibody 1A7. This is an antiidiotype produced by immunizing with an antibody specific for ganglioside GD2, and identifying a hybridoma secreting antibody with immunogenic potential in a multi-step screening process. Also disclosed are polynucleotide and polypeptide derivatives based on 1A7, including single chain variable region molecules and fusion proteins, and various pharmaceutical compositions. When administered to an individual, the 1A7 antibody overcomes immune tolerance and induces an immune response against GD2, which comprises a combination of anti-GD2 antibody and GD2-specific T cells. The invention further provides methods for treating a disease associated with altered GD2 expression, particularly melanoma, neuroblastoma, glioma, soft tissue sarcoma, and small cell carcinoma Patients who are in remission as a result of traditional modes of cancer therapy may be treated with a composition of this invention in hopes of reducing the risk of recurrence. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 08/372,676, filed Jan. 17, 1995; and U.S. Ser. No. 08/591,196, filed Jan. 16, 1996; both of which are hereby incorporated herein in their entirety.... In spite of numerous advances in medical research, cancer remains the second leading cause of death in the United States. Traditional modes of clinical care, such as surgical resection, radiotherapy and chemotherapy, have a significant failure rate, especially for solid tumors. Failure occurs either because the initial tumor is unresponsive, or because of recurrence due to regrowth at the original site or metastasis. Cancer remains a central focus for medical research and development.... Under the hypothesis that neoplastic cells are normally regulated by immune surveillance, an attractive approach is to re-focus the immune system in affected individuals back towards the tumor. Many types of cancers should be susceptible to the immune system, because they express unusual antigens that reflect the oncogenic transformation of the cell. Antibodies or T cells directed against a target antigen specifically expressed on tumor cells may be able to recruit immune effector functions, and thereby eliminate the tumor or mitigate the pathological consequences. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Novel protein related to melanoma-inhibiting protein and uses thereof Inventor(s): Barnes, Thomas M. (Brookline, MA), Pan, Yang; (Bellevue, WA) Correspondence: Jean M. Silveri; MILLENNIUM PHARMACEUTICALS, INC. 75 Sidney Street; Cambridge; MA; 02139; US Patent Application Number: 20020103360 Date filed: February 16, 2001 Abstract: Novel TANGO 130 nucleic acid molecules which encode proteins having homology to melanoma-inhibiting protein are disclosed. In addition to TANGO 130 nucleic acid molecules and proteins, the invention further provides isolated TANGO 130 fusion proteins, antigenic peptides and anti-TANGO 130 antibodies. The invention also provides vectors containing nucleic acid molecules of the invention, host cells into which the vectors have been introduced and non-human transgenic animals in which a TANGO 130 gene has been introduced or disrupted. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/387,462, filed on Sep. 1, 1999, which is a continuation-in-part of U.S. application Ser. No. 09/145,056, filed on Sep. 1, 1998. The contents of each of the applications crossreferenced in this section are incorporated into this disclosure by this reference.... A variety of factors participate in the tightly controlled regulation of cell growth and differentiation. One molecule believed to be involved in such regulation is MelanomaInhibiting Protein (MIA). Human and murine MIA cDNAs were first cloned from malignant melanoma cells and shown to inhibit growth of melanoma cells in vitro (Blesch et al. (1994) Cancer Res. 54:5695). Human MIA cDNA encodes a 24 amino acid signal peptide and a mature 107 amino acid secreted protein, and shares little or no homology with other known proteins.... Cancer cells and embryonic cells are growth inhibited after treatment with MIA, observed as cell cycle arrest accompanied by a rounded up cell morphology and decreased adherence to the substrate. Furthermore, MIA expression is enhanced in developing cartilage and in chondrosarcoma (Bosserhoff et al. (1997) Dev. Dyn. 208:516). Based on this data, a biological role for MIA in embryonic cell growth and morphogenesis has been suggested, and a therapeutic application of MIA in the development of an antitumor therapeutic has been proposed. Additionally, MIA expression correlates with progressive malignancy of melanocytic lesions (Bosserhoff et al. (1997) J. Biol. Chem. 271:490), and MIA protein levels are enhanced in serum of patients with malignant melanoma (Bosserhoff et al. (1997) Cancer Res. 57:3149), supporting another proposed use of MIA as a marker of cancer progression. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Nucleic acid molecule associated immunodetection and immunotherapy
with
prostate
cancer
and
melanoma
Inventor(s): Vielkind, Juergen R. (Vancouver, CA) Correspondence: Leopold Presser, Esq. Scully, Scott, Murphy & Presser; 400 Garden City Plaza; Garden City; NY; 11530; US Patent Application Number: 20020146702 Date filed: May 11, 2001
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Abstract: The present invention relates to the use of isolated nucleic acid molecules associated with prostate cancer and melanoma and compositions derived therefrom. The present invention further relates to methods for diagnosing and treating prostate cancer and melanoma and other related pathological conditions by employing such nucleic acid molecules and compositions. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 09/255,583 filed Feb. 22, 1999, now allowed, which is a divisional of U.S. Ser. No. 08/869,285 filed Jun. 2, 1997 which is a continuation-in-part of U.S. Ser. No. 08/654,641, filed May 28, 1996, now U.S. Pat. No. 5,719,032, which is a continuation-in-part U.S. Ser. No. 07/829,855 filed Jan. 31, 1992, now U.S. Pat. No. 5,605,831, which disclosures are herein incorporated by reference.... The subject invention is related to the use of antibodies, which bind to a unique peptide obtainable from a Xiphophorus melanoma mrk-receptor tyrosine kinase for the diagnosis and therapy of melanoma and prostate cancer. This invention also relates to the use of isolated nucleic acid molecules associated with prostate cancer and melanoma for diagnosing and treating pathological conditions including prostate cancer and melanoma.... The ability to detect and diagnose cancer through the identification of tumor markers is an area of widespread interest. Tumor markers are substances, typically proteins, glycoproteins, polysaccharides, and the like which are produced by tumor cells and are characteristic thereof. Often, a tumor marker is produced by normal cells as well as by tumor cells. In the tumor cells, however, the production is in some way atypical. For example, production of a tumor marker may be greatly increased in the cancer cell. Additionally, the tumor marker may be released or shed into the circulation. Detection of such secreted substances in serum may be diagnostic of the malignancy. Therefore, it is desirable to identify previously unrecognized tumor markers, particularly, tumor markers which are secreted into the circulation and which may be identified by serum assays. It is also desirable to develop methods and compositions which allow determination of the cellular origin of a particular tumor or other proliferative disease, for example by radioimaging techniques. The location of the tumor markers on the surface of the cells, particularly where there is an extracellular domain that is accessible to antibodies (i.e., the domain acts as a receptor for the antibodies), provides a basis for targeting cytotoxic compositions to the receptor. Examples of compositions of interest in such a method include complement fixing antibodies or immunotoxins which bind to the receptor as a means of specifically killing those cells which express the receptor on the cell surface. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Paclitaxel treatment regimen for metastatic melanoma Inventor(s): Helson, Larry; (Quakertown, PA) Correspondence: SALIWANCHIK LLOYD & SALIWANCHIK; A PROFESSIONAL ASSOCIATION; 2421 N.W. 41ST STREET; SUITE A-1; GAINESVILLE; FL; 326066669 Patent Application Number: 20020013362 Date filed: April 18, 2001 Abstract: The invention relates generally to a method of using paclitaxel in a specific Q4D.times.3 schedule and dosage for patients with malignant melanoma. The low riskbenefit ratio of this specific schedule provides a method for therapeutic use for all stages of severity of disease ranging from local resectable tumor to diagnosed widespread malignant melanoma.
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Excerpt(s): The present invention broadly concerns a treatment regimen for patients with local or disseminated malignant melanoma. More specifically, the present invention relates to a paclitaxel treatment schedule and dosages which are different from the standard drug schedule of once every 21 days.... Melanoma was once a rarity in oncological management. An exponential increase in incidence during the past 25 years has made it an important focus for treatment-related research. In 1995 there were an estimated 34,000 new cases and 7,000 deaths. (Wingo, Pa. 1995.) Treatment options and the effectiveness of systemic chemotherapy for advanced melanoma are limited, rendering it a fatal disease. Most agents and combinations of agents are no better than the single agent dacarbazine. (Legha 1990.) The results of scheduling for dacarbazine are quite variable depending upon the number of sequential days of treatment. Evidence is available that suggests that longer treatment schedules are more effective than shorter in producing overall response rates. (Nathanson, L. 1971; McClay E. F. and McClay, M. E., 1996.) These observations may be reflecting the pharmacodynamic characteristics of dacarbazine, particularly its dwell time in the cell and the duration of its biological effects. Based on this same premise, the pharmacodynamics of any drug considered for treatment of this disease must be taken into consideration, and in effect dictates the strategy for its schedule of administration.... Paclitaxel is a natural product extracted from the bark of Pacific yew trees, Taxus brevifolia. It has been shown to have excellent antitumor activity in in vivo animal models. Paclitaxel is a cell cycle specific agent which has as its primary intracellular target the beta subunit of tubulin, and when bound to it promotes and stabilizes the polymerized microtubular state. This causes metaphase arrest which in turn induces apoptotic cell death. Paclitaxel has been approved for the treatment of refractory advanced ovarian cancer and breast cancer; and studies involving other cancers have shown promising results. The results of paclitaxel clinical studies are reviewed by numerous authors (Hajek R. et al., 1996; Bedikian A. Y. et al., 1995; Spencer and Faulds, 1994; and Rowinsky and Donehower, 1991), and also in the references cited therein. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Recombinant oncolytic adenovirus for human melanoma Inventor(s): Yu, De Chao; (Foster City, CA), Li, Yuanhao; (Palo Alto, CA) Correspondence: BOZICEVIC, FIELD & FRANCIS LLP; 200 MIDDLEFIELD RD; SUITE 200; MENLO PARK; CA; 94025; US Patent Application Number: 20030039633 Date filed: January 15, 2002 Abstract: The invention provides melanoma cell specific adenovirus vectors, which preferentially replicate in melanoma cells. Excerpt(s): This application in a continuation-in-part of U.S. patent application Ser. No. 09/814,357, filed Mar. 21, 2001 which claims the benefit of U.S. Provisional Patent Application No. 60/192,015 filed Mar. 24, 2000; and a continuation-in-part of U.S. patent application Ser. No. 09/814,351, filed Mar. 21, 2001 which claims the benefit of U.S. Provisional Patent Application No. 60/192,156 filed Mar. 24, 2000.... The technical field of the invention is methods of using adenoviral vectors for the suppression of melanoma.... Neoplasia, also known as cancer, is the second most common cause of death in the United States. While the survival rates for individuals with cancer have increased considerably in the last few decades, survival of the disease is far from assured. Cancer is a catch-all term for over 100 different diseases, each of which are each
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fundamentally characterized by the unchecked proliferation of cells. Individual cancer cells are also able to break off from the main tumor, or metastasize, creating additional tumors in other regions of the body. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Skin cancer preventive agent Inventor(s): Hibasami, Hiroshige; (Mie, JP), Fuwa, Naozumi; (Fukui, JP), Yamada, Hideyuki; (Fukui, JP), Muramatsu, Koichiro; (Nishio, JP), Jin, Zongxuan; (Nishio, CN) Correspondence: ARENT FOX KINTNER; POLTKIN & KAHN, PLLC; Suite 600; 1050 Connecticut Avenue, N.W. Washington; DC; 20036-5339; US Patent Application Number: 20010053759 Date filed: May 24, 2001 Abstract: The present invention provides a skin cancer preventive agent that inhibits the promotion of carcinogenesis of skin cancer while having high levels of safety and stability as well as being free of adverse side effects. The present invention is characterized by containing sericin. Excerpt(s): The present invention relates to a skin cancer preventive agent that uses natural sericin for its raw material, has high safety and stability, is free of adverse side effects, and can be used in fields such as drugs, over-the-counter drugs, health foods, cosmetics and lotions.... Cancer is the leading cause of death, and it is predicted that the number of persons with cancer will continue to increase in the future. Thus, the discovery of a preventive method for preventing cancer is an extremely important subject. Although a diverse range of methods have been proposed for preventing cancer, chemoprophylaxis of cancer has recently attracted attention.... Chemoprophylaxis of cancer involves primary prevention of cancer that attempts to prevent the initiation and promotion of cancer by application of chemical substances. Those chemical substances for which effects have been confirmed in animal experiments or those that have been found to be effective based on epidemiological results are currently being tested in human subjects. Although chemical substances that prevent cancer are detected from animal experiments, research on chemoprophylaxis using animals is conducted using chemical carcinogenesis models. Although numerous stages of gene mutations are involved in the onset of cancer, carcinogenesis is a two-stage process consisting of initiation and promotion. Thus, chemoprophylactic agents for cancer consist of those that inhibit initiation of carcinogenesis by the application of a cancer chemoprophylactic agent during the initiation stage of an animal chemical carcinogenesis model, and those inhibit promotion of carcinogenesis by application during the promotion stage. Furthermore, cancer preventive agents are normally required to be free of problems with safety and not have any adverse side effects, while also being able to be applied over a long period of time. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Transgenic animal model of basal cell carcinoma Inventor(s): Dlugosz, Andrzej A. (Ann Arbor, MI), Hui, Chi-Chung; (Toronto, CA) Correspondence: MYERS BIGEL SIBLEY & SAJOVEC; PO BOX 37428; RALEIGH; NC; 27627; US Patent Application Number: 20010027566 Date filed: January 11, 2001 Abstract: The present invention provides transgenic non-human animal models of basal cell carcinoma which allows for the characterization of the disease as well as for providing a system for the development and testing of potential treatments. Excerpt(s): This application claims priority from U.S. patent application Ser. No. 60/175,637 filed Jan. 12, 2000.... The present invention relates to transgenic non-human animal models of basal cell carcinoma. More specifically, the present invention is directed to mouse models of basal cell carcinoma allowing for the characterization of the mechanism of the disease as well as for developing and testing potential treatments.... Throughout this application, various references are cited in parentheses to describe more fully the state of the art to which this invention pertains. Full bibliographic information for each citation is found at the end of the specification, immediately preceding the claims. The disclosures of these references are hereby incorporated by reference into the present disclosure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of a melanoma differentiation associated gene (mda 7) for reversing a cancerous phenotype Inventor(s): Fisher, Paul B. (Scarsdale, NY) Correspondence: BAKER BOTTS L.L.P. 44TH FLOOR; 30 ROCKEFELLER PLAZA; NEW YORK; NY; 10112-0228; US Patent Application Number: 20020091098 Date filed: November 21, 2001 Abstract: This invention provides a method for reversing the cancerous phenotype of a cancer cell by introducing a nucleic acid having the melanoma differentiation associated gene (mda-7) into the cell under conditions that permit the expression of the gene so as to thereby reverse the cancerous phenotype of the cell. This invention also provides a method for reversing the cancerous phenotype of a cancer cell by introducing the gene product of the above-described gene into the cancerous cell so as to thereby reverse the cancerous phenotype of the cell. This invention also provides a pharmaceutical composition having the melanoma differentiation associated gene (mda-7) or the gene product of the melanoma differentiation associated gene (mda-7) effective to reverse the cancerous phenotype of a cancer cell and a pharmaceutically acceptable carrier. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 08/696,573, filed Jun. 16, 1996, the content of which is incorporated into this application by reference.... Throughout this application, various references are referred to within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Full bibliographic citation for these references may be found at the end of each series of experiments.... Cancer is a complex multifactor and multistep process involving
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the coordinated expression and suppression of genes functioning as positive and negative regulators of oncogenesis (1-5). Direct cloning strategies, based on transfer of a dominant transforming or tumorigenic phenotype, have identified positive acting oncogenes (6-9). In contrast, the detection and cloning of genes that suppress the cancer phenotype have proven more difficult and elusive (10-15). A direct approach for isolating genes directly involved in regulating growth and differentiation involves subtraction hybridization between cDNA libraries constructed from actively growing cancer cells and cDNA libraries from cancer cells induced to lose proliferative capacity irreversibly and terminally differentiate (13, 14). This experimental strategy has been applied to human melanoma cells, induced to terminally differentiate by treatment with recombinant human interferon.beta. (IFN-9) and mezerein (MEZ), resulting in the cloning of novel melanoma differentiation-associa- ted (mda) genes not previously S described in DNA data bases (13, 14). A direct role for specific mda genes in mediating growth and cell cycle control is apparent by the identification and cloning of mda-6 (1316), which is identical to the ubiquitous inhibitor of cyclin-dependent kinases p21 (17). The importance of p21 in growth control is well documented and this gene has been independently isolated, as WAF-1, CIP-1, and SDI-1, by a number of laboratories using different approaches (18-20). These studies indicate that specific genes associated with proliferative control are induced and may contribute to the processes of growth arrest and terminal differentiation in human cancer cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of azoles for the preventing skin cancer Inventor(s): Enzmann, Harald; (Wuppertal, DE), Fladung, Bernward; (Odenthal, DE) Correspondence: Richard S Bullitt; Bayer Corporation; Box 1910; 36 Columbia Road; Morristown; NJ; 07962-1910; US Patent Application Number: 20020193384 Date filed: June 5, 2002 Abstract: Azoles are suitable for the prevention of radiation-induced skin cancer. Excerpt(s): The invention relates to the use of azoles for the prevention of skin cancer caused by radiation.... According to their wavelength, UV rays are divided into UV-A rays (320-400 nm, UV-A-I: 340-400 nm, UV-A-II: 320-340 nm) or UV-B rays (280-320 nm). Very generally: the harmful effect of UV rays on the human skin increases with decreasing wavelength and increasing exposure time.... UV rays can cause acute and chronic skin damage, the type of damage depending on the wavelength of the radiation. For example, UV-B radiation can cause sunburn (erythema) ranging to the severest of, skin bums. Decreases in enzyme activities, disturbances of the DNA structure and changes in the cell membrane are also known as harmful effects of UV-B rays. UV-A rays penetrate into the deeper layers of the skin, where they can accelerate the ageing process of the skin. Shorter-wave UV-A-II radiation additionally intensifies the development of sunburn. Moreover, UV-A radiation can trigger phototoxic or photoallergic skin reactions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Keeping Current In order to stay informed about patents and patent applications dealing with skin 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 “skin 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 skin cancer. You can also use this procedure to view pending patent applications concerning skin 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 SKIN CANCER Overview This chapter provides bibliographic book references relating to skin cancer. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on skin 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 “skin 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 skin cancer: •
What You Really Need To Know About Moles and Melanoma Source: Baltimore, MD: The Johns Hopkins University Press. 2000. 232 p. Contact: Available from Johns Hopkins University Press. Hopkins Fulfillment Service, P.O. Box 50370, Baltimore, MD 21211-4370. (410) 516-6956. Fax (410) 516-6998. E-mail:
[email protected]. Website: www.jhupbooks.com. PRICE: $14.95 plus shipping and handling. ISBN 0801863945. Summary: This book provides people who have melanoma with the most up to date information on the prevention, diagnosis, and treatment of this form of skin cancer. Part one focuses on the recognition and prevention of melanoma. Topics include the structure of the skin; the features of nonmelanoma skin cancers; the characteristics of pigmented lesions such as freckles, seborrheic keratoses, lentigos, and nevi; and the causes and warning signs of melanoma. One chapter focuses on the risk factors for melanoma, including number of moles; changing, atypical, and congenital moles;
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intense, intermittent sun exposure; prior severe sunburns; melanoma in a close relative; personal history of melanoma; skin type; hair color; age; gender; immune system suppression; prior psoralen and ultraviolet A treatments to the skin; xeroderma pigmentosa; and atypical mole syndrome. Other topics include prevention and early detection of melanoma and education about skin cancer and melanoma. Part two deals with the diagnosis and treatment of melanoma. Chapters discuss removing and treating the primary lesion; determining the stage of the cancer; evaluating and treating regional lymph nodes at the time of diagnosis; and using adjuvant therapy such as immunotherapy, radiation therapy, chemotherapy, vitamins and diet therapy, and lifestyle changes. Other topics include treating melanoma that has metastasized with drugs, surgery, and experimental therapies and managing pain and the end of life. Answers to frequently asked questions about diagnosing and treating melanoma are listed. Part three focuses on unusual noncutaneous and less common forms of cutaneous melanoma and reviews melanoma research. The book contains color photographs and line drawings, a glossary, and a guide to resources such as support and advocacy organizations and websites for people who have melanoma. 11 figures, 2 tables, and 13 color plates. •
Melanoma Prevention, Detection, and Treatment Source: New Haven, CT, Yale University Press, 140 p., 1998. Contact: Yale University Press, New Haven, CT. INTERNET/EMAIL: www.yale.edu/yup/. Summary: Melanoma Prevention, Detection, and Treatment is a guide that examines all aspects of malignant melanoma, but with an emphasis on providing practical information that can save lives by detecting the malignancy early. The book contains eight chapters: (1) Close Encounters with Melanoma; (2) What Is Melanoma?; (3) Who Gets Melanoma and Why; (4) Finding Early Melanoma; (5) If You Have Melanoma; (6) When Melanoma Metastasizes; (7) Tending to Your Spirits; and (8) Future Promise: Prevention of Melanoma. The book also contains two appendices that (1) describe the staging system for melanoma; and (2) present a list of resources for melanoma, including lists of computerized databases, addresses of helpful organizations and support groups, and lists of additional publications.
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Melanoma: Diagnosis and Treatment Source: New Orleans, LA, Louisiana Cancer Consortium, 62 p., 1994. Contact: Louisiana Cancer Consortium, 1430 Tulane Avenue, New Orleans, LA 70112. (504) 588-5518. Summary: Melanoma: Diagnosis and Treatment contains information for physicians about educating their patients and the public about methods of prevention, diagnosis, and treatment for various types of melanoma. Chapters, written by various physicians, contain figures (including color photographs of various melanomas), tables, and references. Contents include (1) introduction (the problem of melanoma, melanoma variants, and implications for the physician); (2) epidemiology of melanoma (incidence, mortality, and survival); (3) risk factors and risk management; (4) evaluation of nevi and guidelines for patient monitoring; (5) diagnosis of melanoma (patient history, physical examination, major growth patterns of melanoma, differential diagnosis, and biopsies); (6) treatment of the melanoma patient (clinical management of malignant melanoma, surgical excision, node dissection, adjunctive therapy, management of advanced of metastatic melanoma, and immune therapy of melanoma); (7) melanoma in dark-
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skinned people (palms, soles, and mucous membranes); (8) prevention of malignant melanoma (excessive sunlight, early detection, and routine skin self-examination); (9) patient education (sources of pamphlets on melanoma); and (10) public awareness efforts (Skin Cancer and Melanoma Detection Month). •
Primary and Secondary Prevention of Malignant Melanoma Source: New York, NY, Karger, Pigment Cell, Volume 11, 130 p., 1996. Contact: S. Karger AG, 26 West Avon Road, P.O. Box 529, Farmington, CT 06085. (800) 828-5479; (860) 675-7834. Summary: Primary and Secondary Prevention of Malignant Melanoma contains articles by world authorities in the fields of primary and secondary prevention of malignant melanoma. The incidence of Malignant melanoma continues to increase steadily, while mortality is also increasing in almost all parts of the world, although the rate of mortality increase is less rapid than that of the morbidity due to earlier detection and treatment of lesions. Primary prevention campaigns are currently aimed at encouraging sensible sun exposure, which is defined as preventing visible sunburn and reducing sun exposure around noon when the ultraviolet light intensity is at its greatest. Secondary prevention efforts devote time and energy to campaigns aimed at earlier diagnosis and prompt treatment. Chapters include (1) Methodological Issues in Research on Primary and Secondary Prevention of Malignant Melanoma, (2) Secondary Prevention of Malignant Melanoma in Europe, (3) Secondary Prevention of Skin Cancer in Australia, (4) Primary Prevention Activities for Malignant Melanoma in the United States, (5) Primary Prevention Activities in the United Kingdom, (6) Programs for the Primary Prevention of Melanoma in Australia, and (7) Evaluation of Programs to Modify Sun Exposure. Secondary prevention efforts may have an effect in 3-5 years, but primary prevention campaigns may not have an effect for 20-30 years. Those persons embarking on primary and secondary prevention of skin cancer campaigns must therefore be extremely careful to put in place good audit measures that will exist for years or even decades.
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 Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “skin cancer” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “skin cancer” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “skin cancer” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
100 Questions and Answers about Melanoma & Other Skin Cancers by Edward F. McClay, et al; ISBN: 0763720364; http://www.amazon.com/exec/obidos/ASIN/0763720364/icongroupinterna
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21st Century Complete Medical Guide to Skin Cancer (Basal and Squamous Cell Carcinoma) - Authoritative Government Documents and Clinical References for Patients and Physicians with Practical Information on Diagnosis and Treatment
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Options by PM Medical Health News; ISBN: 1592480217; http://www.amazon.com/exec/obidos/ASIN/1592480217/icongroupinterna •
American Cancer Society Atlas of Clinical Oncology: Skin Cancer (Book with CDROM) by Arthur J., Md Sober, Frank G., Md, Phd Haluska; ISBN: 1550091085; http://www.amazon.com/exec/obidos/ASIN/1550091085/icongroupinterna
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Atlas of Skin Cancer by Anthony Du Vivier; ISBN: 0397448368; http://www.amazon.com/exec/obidos/ASIN/0397448368/icongroupinterna
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Attitudes to Sunbathing and the Risks of Skin Cancer by Wendy Howard (1997); ISBN: 0752107844; http://www.amazon.com/exec/obidos/ASIN/0752107844/icongroupinterna
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Basal and Squamous Cell Skin Cancers of the Head and Neck by Randal S. Weber (Editor), et al; ISBN: 0683088882; http://www.amazon.com/exec/obidos/ASIN/0683088882/icongroupinterna
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Biology of skin cancer (excluding melanomas) : a series of workshops on the biology of human cancer, report no. 15; ISBN: 9290180633; http://www.amazon.com/exec/obidos/ASIN/9290180633/icongroupinterna
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Chemosurgery : microscopically controlled surgery for skin cancer by Frederic E. Mohs; ISBN: 0398037256; http://www.amazon.com/exec/obidos/ASIN/0398037256/icongroupinterna
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Coping With Melanoma and Other Skin Cancers (Coping) by Wendy Long; ISBN: 0823928527; http://www.amazon.com/exec/obidos/ASIN/0823928527/icongroupinterna
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Cryosurgery for Skin Cancer and Cutaneous Disorders by Sedray A. Zacarian (Editor); ISBN: 0801657075; http://www.amazon.com/exec/obidos/ASIN/0801657075/icongroupinterna
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Cryosurgical Treatment for Skin Cancer by Emanuel G. Kuflik, Andrew A. Gage; ISBN: 089640157X; http://www.amazon.com/exec/obidos/ASIN/089640157X/icongroupinterna
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Dermatologic Formulary: Skin Cancer Unit New York University by Jerome L. Shupack (Editor), et al; ISBN: 0070575215; http://www.amazon.com/exec/obidos/ASIN/0070575215/icongroupinterna
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Practical Management of Skin Cancer by Ronald L. Moy (Editor), et al; ISBN: 0397516045; http://www.amazon.com/exec/obidos/ASIN/0397516045/icongroupinterna
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Protect Your Life in the Sun: How to Minimize Your Exposure to Ultraviolet Sunlight and Prevent Skin Cancer and Eye Disorders by Paul L. Gourley, Gail M. Gourley; ISBN: 0963629719; http://www.amazon.com/exec/obidos/ASIN/0963629719/icongroupinterna
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Saving Your Skin: Prevention, Early Detection, and Treatment of Melanoma and Other Skin Cancers by Barney J. Kenet, et al (1998); ISBN: 1568581246; http://www.amazon.com/exec/obidos/ASIN/1568581246/icongroupinterna
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Skin cancer : basic science, clinical research, and treatment; ISBN: 3540576304; http://www.amazon.com/exec/obidos/ASIN/3540576304/icongroupinterna
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Skin Cancer and Uv Radiation by Peter Altmeyer (Editor), et al; ISBN: 3540627235; http://www.amazon.com/exec/obidos/ASIN/3540627235/icongroupinterna
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Skin Cancer Prevention: Policy Guidelines for Local Authorities; ISBN: 0752109197; http://www.amazon.com/exec/obidos/ASIN/0752109197/icongroupinterna
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Skin Cancer Prevention: Policy Guidelines for Local Authorities; ISBN: 0752113615; http://www.amazon.com/exec/obidos/ASIN/0752113615/icongroupinterna
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Skin Cancer: a Brief Review of Incidence and Causes by Elizabeth Skinner, Meg Price (1997); ISBN: 0752110179; http://www.amazon.com/exec/obidos/ASIN/0752110179/icongroupinterna
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Skin Cancer: A Practical Guide to Surgical Management by Graham B. Clover, et al (2002); ISBN: 1841841730; http://www.amazon.com/exec/obidos/ASIN/1841841730/icongroupinterna
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Skin Cancer: An Illustrated Guide to the Aetiology, Clinical Features, Pathology and Management of Benign and Malignant Cutaneous Tumours by Rona M. MacKie; ISBN: 1853172030; http://www.amazon.com/exec/obidos/ASIN/1853172030/icongroupinterna
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Skin Cancer: Basic Science, Clinical Research and Treatment (Recent Results in Cancer Research, Vol 139) by C. Garbe (Editor), et al; ISBN: 0387576304; http://www.amazon.com/exec/obidos/ASIN/0387576304/icongroupinterna
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Skin Cancer: Cancer Surveys (Cancer Surveys, Vol 26) by J. A. Newton Bishop (Editor), Irene Leigh (Editor) (1996); ISBN: 0879694831; http://www.amazon.com/exec/obidos/ASIN/0879694831/icongroupinterna
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Skin Cancer: Mechanisms and Human Relevance by Hasan, Ph.D. Mukhtar (Editor); ISBN: 0849373581; http://www.amazon.com/exec/obidos/ASIN/0849373581/icongroupinterna
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Skin Cancer: Recognition and Management by Robert A. Schwartz (Editor); ISBN: 0387966129; http://www.amazon.com/exec/obidos/ASIN/0387966129/icongroupinterna
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Skin Cancer: Recognition and Management; ISBN: 3540966129; http://www.amazon.com/exec/obidos/ASIN/3540966129/icongroupinterna
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Skin Cancers (Your Operation) by John Kenealy, Jane Smith; ISBN: 0340669330; http://www.amazon.com/exec/obidos/ASIN/0340669330/icongroupinterna
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Skin Health Information for Teens: Health Tips About Dermatological Concerns and Skin Cancer Risks (Teen Health Series) by Robert Aquinas McNally (Editor), Omnigraphics (2003); ISBN: 0780804465; http://www.amazon.com/exec/obidos/ASIN/0780804465/icongroupinterna
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Slide Atlas of Skin Cancer (Slide Atlas of Diagnostic Oncology) by Michael M. Wick MD PhD; ISBN: 1563750392; http://www.amazon.com/exec/obidos/ASIN/1563750392/icongroupinterna
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Sun Sense: A Complete Guide to the Prevention, Early Detection an d Treatment of Skin Cancer by Perry Robins (1990); ISBN: 0962768804; http://www.amazon.com/exec/obidos/ASIN/0962768804/icongroupinterna
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Sunlight and Skin Cancer : A Scientific American article [DOWNLOAD: PDF] by David J. Leffell (Author), Douglas E. Brash (Author); ISBN: B00006BNN3; http://www.amazon.com/exec/obidos/ASIN/B00006BNN3/icongroupinterna
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The Health Care Costs of Skin Cancer Caused by Ultraviolet Radiation by Bridger M. Mitchell, James R. Vernon (1987); ISBN: 9998907500; http://www.amazon.com/exec/obidos/ASIN/9998907500/icongroupinterna
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The Official Patient's Sourcebook on Skin Cancer: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597834873; http://www.amazon.com/exec/obidos/ASIN/0597834873/icongroupinterna
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The Skin Cancer Answer by I. William Lane, et al (1999); ISBN: 0895298651; http://www.amazon.com/exec/obidos/ASIN/0895298651/icongroupinterna
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The Skin Cancer Breakthrough Program by Kurt Greenberg; ISBN: 0972448209; http://www.amazon.com/exec/obidos/ASIN/0972448209/icongroupinterna
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Treatment of Skin Cancer by R.G. Freeman, J. M. Knox Freeman; ISBN: 0387039597; http://www.amazon.com/exec/obidos/ASIN/0387039597/icongroupinterna
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Treatment Planning and Delivery in Ericksonian Hypnotherapy: Psychological Sequelae of Skin Cancer by Lankton; ISBN: 0876303548; http://www.amazon.com/exec/obidos/ASIN/0876303548/icongroupinterna
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Understanding Skin Cancer; ISBN: 1870403355; http://www.amazon.com/exec/obidos/ASIN/1870403355/icongroupinterna
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Understanding Skin Cancer Chart by Anatomical Chart (2003); ISBN: 1587793571; http://www.amazon.com/exec/obidos/ASIN/1587793571/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 “skin 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 •
Cryosurgery of skin cancer and cryogenic techniques in dermatology. Author: Zacarian, Setrag A.,; Year: 1969; Springfield, Ill., Thomas [c1969]
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Current concepts in the management of skin cancer Author: Robins, Perry,; Year: 1978; New York, N.Y.: Clinicom, [1978?]
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Environmental UV-radiation, risk of skin cancer, and primary prevention: internationaler Kongress und Klausurtagung der Strahlenschutzkommission 6.-8. Mai 1996, Hamburg: Zusammenfassung und Bewertung der Ergebnisse durch die Strahlenschutzkommission: conference reports Author: Volkmer, B.; Year: 1996; Stuttgart: Gustav Fischer, c1996; ISBN: 3437251880
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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. 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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Experimental researches on precancerous changes in the skin and skin cancer; an investigation of the local action of tar on the skin and its different elements, with special reference to the importance of nerves and vessels for the development of precancerous alterations in the skin and of skin cancer. Author: Guldberg, Gustav,; Year: 1931; Copenhagen, Levin; Munksgaard, 1931
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Freckles, moles, sores & sunspots: guidelines for the management of skin cancer Author: Australian Cancer Society.; Year: 1990; [Carlton, Vic.?: Anti-Cancer Council of Victoria], c1990
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Incidence of nonmelanoma skin cancer in the United States Author: Scotto, Joseph.; Year: 1983; [Bethesda, Md.]: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, National
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Links between exposure to ultraviolet radiation and skin cancer Author: MacKie, Rona M.; Year: 1987; London: Royal College of Physicians, c1987; ISBN: 0900596708
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Measurements of ultraviolet radiation in the United States and comparisons with skin cancer data Author: Scotto, Joseph.; Year: 1976; [Bethesda, Md.]: U. S. Dept. of Health, Education, and Welfare, Public Health Service, National Institutes of Health, National
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Melanoma and skin cancer; proceedings. [Editor: W. H. McCarthy]. Author: McCarthy, W. H.; Year: 1972; Sydney, Blight [1972]
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Selected abstracts on ultraviolet-induced skin cancer Author: Urbach, Frederick,; Year: 1984; [Bethesda, Md.]: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, National
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Skin cancer: an illustrated guide to the aetiology, clinical features, pathology, and management of benign and malignant cutaneous tumours Author: MacKie, Rona M.; Year: 1989; London: M. Dunitz; Chicago: Year Book Medical Publishers, c1989; ISBN: 0815157169 http://www.amazon.com/exec/obidos/ASIN/0815157169/icongroupinterna
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Skin cancer: the next decade Author: Rouse, I.; Year: 1990; Western Australia: Health Dept. of Western Australia, 1990
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Skin cancer as seen & treated in private practice. Author: National Disease and Therapeutic Index.; Year: 1968; Ambler, Pa., Lea Associates, 1968
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Skin cancer education materials: selected annotations Author: Cancer Information Clearinghouse.; Year: 1978; [Bethesda, Md.]: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, [1978]
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Skin cancer of the scrotum in Illinois: surveillance of a sentinel occupational cancer Author: Alo, Celan J.; Year: 1988; [Springfield, Ill.]: Division of Epidemiologic Studies, Illinois Dept. of Public Health, [1988]
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Skin cancer, by Henry H. Hazen... with ninety-seven text illustrations, and one colored frontispiece. Author: Hazen, H. H. (Henry Honeyman),; Year: 1916; St. Louis, C. V. Mosby company, 1916
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Special report on ingested inorganic arsenic: skin cancer, nutritional essentiality Author: Levine, Tina.; Year: 1988; Washington, DC: Risk Assessment Forum, U.S. Environmental Protection Agency, [1988]
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The health care costs of skin cancer caused by ultraviolet radiation Author: Mitchell, Bridger M.; Year: 1987; Santa Monica, CA: Rand, [1987]
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Treatment of skin cancer [by] Robert G. Freeman [and] John M. Knox. Author: Freeman, Robert G.,; Year: 1967; New York, Springer [c1967]
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Chapters on Skin Cancer In order to find chapters that specifically relate to skin cancer, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and skin 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 “skin cancer” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on skin cancer: •
Chapter 208: Skin Cancers Source: in Berkow, R., ed. The Merck Manual of Medical Information: Home Edition (online version). Rahway, NJ: Merck and Company, Inc. 2000. 5 p. Contact: Available online from Merck and Company, Inc. (800) 819-9456. Website: www.merck.com/pubs/mmanual_home/contents.htm. Also available from your local book store. PRICE: $29.95 plus shipping. Summary: This chapter provides the general public and people who have skin cancer with information on the symptoms, diagnosis, and treatment of basal and squamous cell carcinoma, melanoma, Kaposi's sarcoma, and Paget's disease. Basal cell carcinoma is a cancer that usually develops on skin surfaces exposed to sunlight. The tumors originate in the lowest layer of the epidermis and begin as very small, shiny, firm, raised growths that enlarge very slowly. These tumors may ulcerate or form scabs in the center. The border of a basal cell carcinoma sometimes looks pearly white. The cancer may alternately bleed and form a scab and heal. Basal cell carcinomas usually do not invade and destroy surrounding tissues. A biopsy can confirm the diagnosis. The cancer can be removed by scraping and burning it with an electric needle or by cutting it out. Squamous cell carcinoma usually develops on sun exposed areas but may grow anywhere on the body. This form of cancer originates in the middle layer of the epidermis and begins as a red area with a scaly, crusted surface that does not heal. Most squamous cell carcinomas affect only the tissue around them, but some may spread to other parts of the body. A biopsy is performed to differentiate squamous cell cancer from similar looking diseases. Treatment is the same as for basal cell carcinoma. Melanoma, a cancer that originates in the pigment producing cells of the skin, can begin as a new, small, pigmented skin growth or can develop from existing pigmented moles. Melanoma spreads rapidly to other parts of the body. A biopsy is performed to confirm the diagnosis. Surgery can remove the entire melanoma, and the cure rate is close to 100 percent if the melanoma has not spread. Chemotherapy is used to treat melanomas that have spread, but the cure rate is low. Kaposi's sarcoma, which originates in the blood vessels, has two forms. One is a disease of the elderly, usually of European, Jewish, or Italian heritage, in whom the cancer grows very slowly and rarely spreads. The second form occurs in children and young men in equatorial Africa and in people with acquired immunodeficiency syndrome. The first form may not need any treatment, while the second has been treated with chemotherapy and interferon alfa. Paget's disease is a rare type of skin cancer that originates in glands in or under the skin. It is treated by surgically removing the growth.
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Part II: Policies to Promote Sun Safety and Prevent Skin Cancer Source: in Fit, Healthy, and Ready to Learn: A School Health Policy Guide. Alexandria, VA, National Association of State Boards of Education, pp. 1-30, November 2002. Contact: National Association of State Boards of Education, 277 South Washington Street, Suite 100, Alexandria, VA 22314. (800) 220-5183; (703) 684-4000. FAX: (703) 8362313. INTERNET/EMAIL: http://www.nasbe.org/catalog.html. Summary: Part II: Policies to Promote Sun Safety and Prevent Skin Cancer, a chapter in Fit, Healthy, and Ready to Learn: A School Health Policy Guide, is written to assist state and local decision-makers in establishing effective policies to help students adopt and maintain lifelong sun safety habits. It is a supplementary chapter to Part I: General School Health Policies, Physical Activity, Healthy Eating, and Tobacco-use Prevention. The chapter offers (1) sample policy language that reflects best practices; (2) scientific data, quotations, and excerpts from actual state and local policies; (3) extensive lists of key technical assistance resources; and (4) guidance on schools' legal obligation to protect staff members who spend significant time outdoors, and balancing sun safety practices with students' need for physical activity. Five chapters are (1) Purpose and Goals, which focuses on the importance of making a strong statement of purpose and goals in order to provide a firm foundation for sound policy; (2) Sun Safety Education, which focuses on instructional program design, lesson reinforcement, and teacher preparation; (3) Outdoor Activities and the School Environment, which focuses on access to shade and scheduling physical education class and other outdoor activities; (4) Sun Safety for School Staff, which focuses on the school nurse's role and ideas for school nurses to promote sun protection at school; and (5) Family and Community Involvement, which focuses on working with schools to establish opportunities for school-based sun safety programs.
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Addressing Skin Cancer Prevention With Outdoor Workers Source: in Promoting Men's Health: A Guide for Practitioners. Davidson, N. Lloyd, T. eds. London, United Kingdom, Bailliere Tindal, pp. 177-187, 2001. Contact: Harcourt Publishers Limited, Harcourt Place, 32 Jamestown Road, London NWI 7BY, United Kingdom. Summary: Addressing Skin Cancer Prevention with Outdoor Workers, a chapter in Promoting Men's Health: A Guide for Practitioners, describes a pilot program designed to influence the attitudes, knowledge, and behaviors of outdoor workers employed in the United Kingdom (UK) toward reducing their sun exposure. The specific structural components of the project were (1) an initial participatory workshop, (2) a followup workshop, and (3) a meeting with management. The workshops were conducted on employers' premises and at times identified by employers as convenient. The goals of the participatory workshops were to (1) examine workers' attitudes, knowledge, and behavior regarding tanning and sun safety; (2) provide information about the risks of solar radiation and skin cancer and effective protection measures; (3) examine the feasibility of sun protection at work; and (4) provide information about early detection of skin cancer. Results of an evaluation of the project indicated that (1) 68 percent of the workers became more aware of the dangers of sun exposure after the initial workshops and 35 percent had learned how to protect their skin from sun exposure, (2) 69 percent of the workers said they would make efforts to protect themselves better in the sun after the initial workshops, and (3) 63 percent of the workers were happy with the way the workshops were operated. As a result of the meeting with company management, management agreed to (1) provide free and subsidized sunscreen for their outdoor
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workers, (2) change workers work uniforms to offer more sun protection, (3) write sun safety recommendations into company Health and Safety manuals, and (4) recommend that similar sun safety workshops be conducted with all company staff. The authors discuss how to address a male audience and barriers to overcome in addressing health promotion activities to males. As part of the project, a resource package called Addressing Sun Safety with Outdoor Workers: A Workplace Intervention Pack, was developed and piloted nationally in collaboration with the Health Education Authority. •
Melanoma Skin Cancer Source: in Run the Good Race: Cancer Prevention and Control in Missouri. Jefferson City, MO, Missouri Department of Health, Bureau of Cancer Control, pp. 20-21, 2000. Contact: Missouri Department of Health, Bureau of Cancer Control, P.O. Box 570, Jefferson City, MO 65102-0570. (800) 316-0935. Summary: Melanoma Skin Cancer, a chapter in Run the Good Race: Cancer Prevention and Control in Missouri, indicates that Missouri ranks 21st highest in the United States for melanoma skin cancer deaths. The main risk factors include (1) exposure to the ultraviolet radiation in sunlight; (2) use of tanning beds and sun lamps, even as little as 1 to 3 times a year; (3) working with exposure to certain chemicals, such as vinyl chloride and PCB's; and (4) being genetically predisposed with fair or red hair, blue eyes, and pale complexion. Those most at risk for this disease include blond or red-headed white women age 65 or older. Those more likely to die are white men over the age of 65 years. Whites are nine times more likely to die from melanoma than African Americans. The death rate for men is twice that of women. Persons over age 65 years are two times as likely to die from melanoma as people age 45 to 64 years, and eight times more likely to die than people under age 45 years.
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Some Economists' Thoughts About Prevention of Skin Cancer Source: in Epidemiology, Causes and Prevention of Skin Diseases. Grob, J.J. Stern, R.S. MacKie, R.M. Weinstock, W.A. eds. Oxford, England, Blackwell Science Ltd., pp. 20-26, 1997. Contact: Blackwell Science, Inc., Commerce Place, 350 Main Street, Malden, MA 021485018. (800) 759-6102; (617) 388-8250. FAX: (617)388-8255. Summary: Some Economists' Thoughts About Prevention of Skin Cancer, a chapter in Epidemiology, Causes and Prevention of Skin Diseases, deals with two issues successively in order to present some possible contributions of economists to the prevention of skin cancer: (1) Cost-effectiveness, and (2) to understand what can be done to effectively change sun-related attitudes and behaviors. The cost-effective analysis algorithm to choose between interventions calls for ranking the health interventions in terms of their cost , going from lowest to highest total cost, and removing from the list any health intervention that costs the same as a prior intervention but produces lower incremental health benefits. Next, compute the incremental cost-effectiveness ratios of one intervention in comparison with the previous one on the list. Eliminate from the list any health intervention with an incremental cost-effectiveness ratio greater than that of the next intervention on the list. Regarding rational avoidance of ultraviolet radiation, individual subjective judgements of relative risk differ markedly from objective expert assessments. Some of the reasons individuals maintain exposure to the sun, which would be considered excessive from a public health point of view, include a lack or misinterpretation of probabilistic information or an overconfidence in personal judgement and desire for certainty. Individuals may attach different values to the
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outcomes and may have different preferences regarding risk per se. Increasing information and risk awareness is a necessary condition, but it is not a sufficient condition for changing individual behaviors. Media campaigns must be considered as one component of structured programs, including health care professionals' contribution to secondary prevention. •
Skin Cancer II: Nonmelanoma Skin Cancer Source: in Challenge of Dermato-epidemiology. Williams, H.C. Strachan, D.P. eds. Boca Raton, FL, CRC Press LLC, pp. 209-222, 1997. Contact: CRC Press LLC, 2000 Corporate Boulevard, NW., Boca Raton, FL, 33431. Summary: Skin Cancer II: Nonmelanoma Skin Cancer, a chapter in the Challenge of Dermato-epidemiology, discusses nonmelanoma skin cancer (NMSC), including incidence, mortality, risk factors, and prevention. NMSC includes basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and many other skin cancers. Dermatologists may find the term NMSC awkward since the different types of NMSC's have different clinical manifestations, pathological features, clinical course, and prognosis. The most challenging problem is that epidemiological data are mainly for BCC and SCC. BCC and SCC are the most common malignant diseases in the United States. A lack of quality population databases makes it hard to study and find the incidence of NMSC. The minimal number of new cases of NMSC among whites in the United States is 500,000 per year. The maximum may be more than 2 million. NMSC among blacks is rare. Australia has the highest incidence of NMSC in the world. NMSC's recurrence rate is low and metastasis is rare. Mortality rates of BCC and SCC in the United States are 0.10 and 0.26 per 100,000 persons per year, respectively. Mortality rates in the United States are decreasing. Based on the Australian estimate, the cost of medical care for NMSC in the United States is expected to exceed $2 billion each year. Whites with fair skin are most at risk for NMSC. Sun exposure and sun damage are the most important risk factors. Men, elderly persons, and those living in tropical or subtropical regions are more likely to be at risk. Many researchers speculate that the depleting ozone levels and corresponding increase in ultraviolet radiation is linked to increasing rates of NMSC. Other risk factors include (1) trauma or injury, (2) burns, (3) viral infections, (4) chronic dermatoses, and (5) family history. Prevention with the use of sunscreens and protective clothing has been advocated, but its long-term efficacy has not yet been confirmed. Further research is needed to (1) find the efficacy of preventive measures, (2) find the efficacy of treatment, (3) generate separate sets of epidemiological data for each NMSC, and (4) generate true population-based epidemiological data of skin cancer.
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Skin Cancer I: Melanoma and Nevi Source: in Challenge of Dermato-epidemiology. Williams, H.C. Strachan, D.P. eds. Boca Raton, FL, CRC Press LLC, pp. 191-207, 1997. Contact: CRC Press LLC, 2000 Corporate Boulevard, NW., Boca Raton, FL, 33431. Summary: Skin Cancer I: Melanoma and Nevi, a chapter in the Challenge of Dermatoepidemiology, discusses melanoma and dysplastic nevus, including incidence, prognosis, variations in when melanoma occurs, and prevention. Melanoma is the malignant neoplasm arising from melanocytes or nevomelanocytes. It is the leading cause of mortality among skin conditions in the United States, and it tends to affect a disproportionate number of younger people when compared to other cancers. Dysplastic nevi are considered by some to be intermediate steps in the reversible process of progression to malignancy. Melanoma occurs among all racial and ethnic groups, but
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more frequently among light-skinned, Caucasian populations. Melanoma incidence increases with age, but is more common among young adults. Women tend to have more tumors on their legs; men have more on their scalp and ears. Prognosis depends on the extent of the disease at the time of diagnosis. Long-term survival is over 75 percent for those with no metastases, but only 15 to 20 percent for those with regional spreading. Long-term survival is greater than 90 percent if the Breslow thickness of a lesion is less than 1 millimeter (mm), but less than 50 percent if the thickness is greater than 4 mm. The ethnic and racial groups in temperate climates are most susceptible to melanoma, but melanomas occur more frequently in equatorial climates. Some data show that melanoma incidence and mortality are increasing in the United States, but trends are not clear. Research to explain these variations has led to a greate r understanding of risk factors: (1) Family history, (2) having dysplastic nevi, (3) sun exposure and sunburn, (4) immunosuppression, (5) upper social class, and (6) indoor occupations. Reducing melanoma mortality is the most important public health goal for dermatology in light-skinned populations. Primary prevention involves (1) reducing exposures that cause melanoma, including sun exposure and exposure to artificial ultraviolet light; (2) use of protective clothing; and (3) sunscreen use. •
Skin Cancer and Melanoma Source: in Cancer Screening. Reintgen, D.S. Clark, R.A. eds. St. Louis, MO, Mosby-Year Book, Inc., pp. 168-195, 1996. Contact: Mosby-Year Book, Inc., 11830 Westline Industrial Drive, St. Louis, MO 63146. Summary: Skin Cancer and Melanoma, a book chapter in Cancer Screening, discusses a wide range of issues related to screening, prevention, and primary care for this disease. The 13 sections in the chapter address (1) the mortality rate for melanoma, which has doubled in the last 35 years, with an increase of approximately 5 percent per year in the older white population; (2) definitions of case finding, screening, and surveillance, the early detection methods for skin cancer; (3) the efficacy of screening, which uses data from Australia and Scotland to explain that the need for screening is based on increasing melanoma incidence and mortality rates and addresses detection of thin melanomas, secondary lesions, prophylactic lesion removal, and tumor thickness at diagnosis; (4) local and national skin cancer education and screening programs sponsored by the American Academy of Dermatology; (5) melanoma control activities in Europe, which include primary prevention and early detection programs; (6) primary prevention of malignant melanoma, which can include public education campaigns that advise sun avoidance and sensible sun exposure; (7) pitfalls of screening programs, including the fact that perhaps two-thirds of melanomas arise without any antecedent lesion; (8) highrisk populations, which include family members of persons with dysplastic nevus syndrome, persons with a history of melanoma, persons with a number of atypical nevi, persons who live in a geographic area with high incidence or mortality from melanoma, and populations with thick primary melanomas; (9) the potential effectiveness of incorporating a thorough skin examination into a routine physical examination; (10) the identification of the melanoma/dysplastic nevus gene, investigative efforts, and ethical considerations; (11) future guidelines for primary care, which may include either a punch biopsy or small excisional biopsy conducted in the physician's office; (12) the cost-effectiveness of diagnosing melanoma at the thin stage; and (13) the need for further research. The authors conclude that primary prevention programs will play an important part in reducing the incidence of melanoma.
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Screening for Skin Cancer: Including Counseling to Prevent Skin Cancer Source: in Guide to Clinical Preventive Services: Report of the U.S. Preventive Services Task Force. Second Edition. US Preventive Services Task Force. Baltimore, MD, Williams and Wilkins, pp. 141-152, 1996. Contact: Williams and Wilkins, 351 West Camden Street, Baltimore, MD 21201-2436. Summary: Screening for Skin Cancer: Including Counseling to Prevent Skin Cancer, a book chapter in Guide to Clinical Preventive Services: Report of the U.S. Preventive Services Task Force, presents recommendations for routine screening for skin cancer and discusses skin cancer epidemiology, the accuracy of screening tests, and the effectiveness of early detection in reducing skin cancer morbidity and mortality. Each year, over 800,000 new cases of skin cancer are diagnosed. Over 95 percent of skin cancers are basal cell (BCC) and squamous cell carcinomas (SCC), which are highly treatable and rarely metastasize. Malignant melanoma (MM) is a less common but far deadlier skin cancer. The principal screening test for skin cancer is physical examination of the skin by a clinician. The true sensitivity and specificity of the skin examination are unknown. Compared to dermatologists, nondermatologists make significantly fewer correct diagnoses of skin lesions. Patient self-examination is less accurate than physician examination. Early treatment may reduce morbidity and disfigurement for BCC and SCC, but there are no such studies to date. For MM there have also been no controlled trials evaluating the impact of screening on morbidity or mortality. If clinician screening does result in detection of less advanced MM, mortality might be reduced. Primary prevention of skin cancer may involve limiting exposure to solar radiation or applying sunscreen preparations. Screening recommendations from various groups include monthly skin self-examination and regular physician skin examination for all adults, patient education, use of skin protection, and avoidance of sun exposure. There is fair evidence of the efficacy and safety of sun avoidance and use of protective clothing, and weaker evidence to support avoiding artificial tanning devices. There is also fair evidence that sunscreens are efficacious in preventing SCC precursors, but data are limited on the ability to sunscreens to prevent skin cancer.
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Epidemiology of Sun Exposure and Skin Cancer Source: in Skin Cancer. Leigh, I.M. Newton Bishop, J.A. Kripke, M.L. eds. Plainview, NY, Cold Spring Harbor Laboratory Press, pp. 133-153, 1996. Contact: Cold Spring Harbor Laboratory Press, 10 Skyline Drive, Plainview, NY 118039729. (800) 843-4388. FAX: (516) 349-1946. INTERNET/EMAIL: www.cshl.org.
[email protected]. Summary: Epidemiology of Sun Exposure and Skin Cancer, a chapter in Skin Cancer, reviews and discusses the epidemiologic evidence that sun exposure causes melanoma and nonmelanocytic skin cancer. The chapter discusses (1) relationships between ambient solar radiation and the incidence of melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC), including the influence of latitude, migration, and ambient solar radiation accumulated or averaged over all places of residence; (2) associations of melanoma, BCC, and SCC with sun sensitivity; (3) relationships of melanoma, BCC, and SCC with body site; (4) associations of melanoma, BCC, and SCC with sun exposure, including the influence of total exposure and exposure on working and nonworking days, sunburn, and exposure/response relationships; (5) associations of melanoma, BCC, and SCC with benign sun-related conditions; and (6) the influence of protective measures on the incidence of melanoma, BCC, and SCC. Melanoma, BCC, and SCC occur more frequently among people living in areas of high ambient solar
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irradiance and in sun-sensitive people. They occur with highest density on body sites usually exposed to the sun and are more frequent in people with benign sun-related conditions. Melanoma is more frequent in people with high sun exposure in an intermittent pattern, but the evidence for associations of personal sun exposure with BCC and SCC is inconsistent. There is little evidence that protection against the sun protects against any of these skin cancers, but this issue is difficult to study epidemiologically. BCC and SCC appear to differ in the shape of their response to sun exposure. BCC appears to show a plateau in risk after moderate exposure levels (and the same has been proposed for melanoma). The risk of SCC, however, appears to continue to increase up to the highest exposure levels. •
Skin Cancer: Prevention and Control Source: in Cancer Prevention and Control. Greenwald, P. Kramer, B.S. Weed, D.L. eds. New York, NY, Marcel Dekker, Inc., pp. 611-640, 1995. Contact: Marcel Dekker, Inc., 270 Madison Avenue, New York, NY 10016. Summary: Skin Cancer: Prevention and Control, a chapter in Cancer Prevention and Control, discusses the prevention and control of malignant melanoma and nonmelanoma skin cancer (NMSC). Risk factors for melanoma are (1) family history, and (2) sunlight or ultraviolet radiation (UVR) exposure. The 5-year survival rates decline steadily as the stage of melanoma at diagnosis increases. Metastatic disease is generally incurable and associated with a median survival of 6 months. Melanoma control programs should target middle-age and older white men who are at greatest risk for late-stage disease and mortality. Methods of intervention include (1) education, (2) screening and early detection, (3) use of sunscreens and primary prevention, and (4) preservation of the ozone layer. Behavior change with respect to reduced sunlight exposure is the main defining criterion for a successful melanoma control program. The authors examine international trends in incidence, mortality, and tumor thickness, and review the major preventive strategies in (1) Australia, (2) New Zealand, (3) the United Kingdom, (4) the Netherlands, and (5) the United States. Worldwide melanoma control programs that include primary prevention, education, and screening activities have only begun an evaluation process. Further research is needed. NMSC is the most common cancer in humans. The two most common forms are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC and SCC account for an estimated 700,000 cases each year in the United States. The main risk factor for NMSC is UVR exposure. NMSC causes few deaths, but its prevalence and potentially invasive nature cause substantial morbidity. Future control of NMSC requires broad-scale interventions using primary and secondary prevention approaches. The main goal of primary prevention is to reduce UVR exposure, particularly among children and adolescents. The authors conclude with a discussion of special conditions with high skin cancer rates.
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Skin Cancer Screening in Massachusetts: The Program and Methodologic Questions Source: in Epidemiologic Aspects of Cutaneous Malignant Melanoma. Gallagher, R.P. Elwood, J.M. eds. Norwell, MA, Kluwer Academic Publishers, pp. 289-303, 1994. Contact: Kluwer Academic Publishers, 101 Philip Drive, Assinippi Park, Norwell, MA 02061. Summary: Skin Cancer Screening in Massachusetts: The Program and Methodologic Questions, a book chapter in Epidemiologic Aspects of Cutaneous Malignant Melanoma, addresses issues surrounding the practice of melanoma/skin cancer screening and education in the United States. The chapter (1) explores the aspects of
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melanoma that necessitate broadening rigid textbook definitions of cancer screening as they apply to skin; (2) describes the rationale behind combining skin cancer screening and education; (3) addresses the concrete issues of evaluation of the American Academy of Dermatology (AAD) program, particularly in Massachusetts; and (4) discusses the public health policy recommendations for skin cancer screening. The AAD began an annual, no-cost skin cancer screening and education program in 1985 in which local and national media publicize risk factors and warning signs for skin cancer and broadcast the availability of no-cost screening clinics. Through 1992, almost 560,000 Americans have been screened in this process and millions more have heard about warning signs of melanoma. Questions addressed by the chapter include (1) do textbook definitions of screening apply to skin cancer; (2) how publicity affects mass screening; (3) which populations should be screened; (4) is the visual examination a valid cancer screening tool; (5) how many confirmed skin cancers are found during screening; (6) is screening for nonmelanoma skin cancer justified; (7) can it be proved that screening saves lives; and (8) should melanoma and skin cancer screening be general health policy? Theoretically there is a broad appeal for screening for skin cancer, but there is no specific evidence to show that it is effective currently. More data are needed to prove definitively that these efforts improve early detection and save lives. •
Skin Cancer and Protection of the Skin Source: in Clinical Preventive Medicine, Matzen, R.N. Lang, R.S. St. Louis, MO, MosbyYear Book, Inc., pp. 929-935, 1993. Contact: Mosby-Year Book, Inc., 11830 Westline Industrial Drive, St. Louis, MO 63146. Summary: Skin Cancer and Protection of the Skin, a book chapter in Clinical Preventive Medicine, states that skin cancer is the most common type of malignancy, with a 30-40 percent prevalence. Epidemiological data support a causal role for sun exposure in the development of basal cell and squamous cell carcinomas. Sun exposure also contributes to the formation of melanoma, a potentially lethal form of skin cancer. Acute effects of sunlight and sun exposure include sunburn, photoallergic and phototoxic reactions, altered immunoreactivity, and a variety of photosensitivity disorders. Chronic, longterm effects of sunlight and sun exposure include photoaging (dermatoheliosis or actinic elastosis), precancerous changes (solar/actinic keratoses), and photocarcinogenesis (basal and squamous cell carcinomas and melanoma). Preventive measures include skin typing, use of sunscreens, systemic photoprotectants (which have had limited success), and retinoids. Skin cancer screening is important in the early detection of any skin cancer and self-examination should be taught to everyone. Regular self-examination is the best way to become familiar with the many moles and spots on the skin. A simple way to remember the features that make a mole suspicious for malignancy is to think of A-B-C-D, for asymmetry, border (irregularity), color (nonuniformity of pigmentation), and diameter (greater than 6 mm). Cutaneous photoprotection by sunscreens and opaque sunscreens represents the best preventive measure against the acute and chronic effects of the sun on the skin.
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Screening for Melanoma/Skin Cancer in the United States Source: in Cancer Screening. Miller, A.B. Chamberlain, J. Day, N.E. Hakama, M. Prorok, P.C. eds. Cambridge, England, Cambridge University Press, pp. 267-278, 1991. Contact: Press Syndicate of the University of Cambridge, 40 West 20th Street, New York, NY 10011-4211.
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Summary: Screening for Melanoma/Skin Cancer in the United States, a chapter in Cancer Screening, reviews the rationale for screening for melanoma/skin cancer, presents data available to date, and raises questions and projects trends for the future. The optimal measure of the efficacy of screening for cancer is the reduction of mortality. However, for melanoma, a prospective trial that can demonstrate reduced mortality may require followup of several hundred thousand people over many years. The visual examination is the only screening test for melanoma/skin cancer. While dermatologists regard the visual examination as an accurate means of detecting melanoma/skin cancer, few data exist on its validity. At least 12 published studies examined melanoma/skin cancer screening in the United States. As yet, however, no information exists regarding whether screening leads to decreased morbidity or mortality from melanoma or nonmelanoma skin cancer. The integration of a skin examination into a routine physical examination by primary care providers may be the best strategy for reducing skin cancer morbidity and mortality. Screening in this way serves as an add-on to ongoing multiphasic screening by primary care providers. Screening may also be done at the workplace, at health fairs, by self-screening, and through the targeting of high-risk persons. •
Occupational Skin Cancer Source: in Occupational Skin Disease. Adams, R.M. New York, NY, Grune and Stratton, pp. 82-98, 1983. Contact: W.B. Saunders and Company, Curtis Center, Independence Square West, Philadelphia, PA 19106-3399. (800) 545-2522. Summary: Occupational Skin Cancer, a book chapter in Occupational Skin Disease, discusses the incidence of occupational skin cancer, occupational cutaneous carcinogens, the mechanism of carcinogenic action, cocarcinogenesis, latency, and the causes of occupational skin cancer. The incidence of skin cancer from all causes in the United States is estimated at approximately 300,000 new cases annually, or one-third of the 900,000 new cases of cancer diagnosed each year. Substances considered as occupational cutaneous carcinogens include ultraviolet light, polycyclic hydrocarbons, ionizing radiation, inorganic arsenic, and physical trauma. With few exceptions, carcinogens must be converted to active forms by some biochemical, enzymatic action. Most carcinogens bind with deoxyribonucleic acid and other cellular macromolecules. The term cocarcinogenesis has been used to describe a variety of phenomena by which tumors are produced by more than one agent, acting together or serially. Cocarcinogens include anthralin, Tween-80, diethylstilbestrol, tryptophane, saccharin, phenobarbital, and croton oil. Variation exists among the latent periods of various chemical carcinogens, depending on the potency, intensity of contact, and individual susceptibility. Ultraviolet radiation causes the greatest number of occupational skin cancers. Prevention of skin cancer consists of skin protection by sunscreening agents, protective clothing, and avoidance of unnecessary sunlight exposure. Ultraviolet radiation is also a potent promoter in tar carcinogenesis. The aromatic hydrocarbons in coal tar fractions that are chiefly responsible for the development of skin cancer are 3,4benzpyrene, dibenzanthracene, and others. Exposure to fumes from tar and asphalt causes changes in the skin, but can take from 1 year to more than 20 years to develop. Methods of prevention include substitution of a noncarcinogenic oil, engineering controls, employee education, good personal hygiene, and periodic physical examination of workers. Inorganic arsenic has also been studied as a cause of skin cancer. Workers potentially exposed to arsenic include painters, semiconductor component makers, herbicide makers, and pharmaceutical drug makers. Numerous
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studies have reported cancer of the skin from x-rays. Occupational sources for ionizing radiation include radiation curing of plastics, manufacture of electronic tubes, nuclear power plants, medical diagnosis and treatment, uranium mining, and sterilization of materials. Skin cancer arising from a single trauma has been a controversial subject for many years, but litigation resulting from malignant tumors allegedly caused by a single injury has been increasing since the 1950's. Unfortunately, in compensation proceedings, scientific fact has less importance than the opinion that a cancerous lesion could reasonably originate from a traumatic event. •
Skin Cancer in the Workplace Source: in Current Concepts in Cutaneous Toxicity: Proceedings of the Fourth Conference on Cutaneous Toxicity, Washington, DC, May 9-11, 1979. Drill, V.A. Lazar, P. eds. Orlando, FL, Academic Press, pp. 243-260, 1980. Contact: Academic Press, Inc., 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 321-5068. Summary: Skin Cancer in the Workplace, a book chapter in Current Concepts in Cutaneous Toxicity: Proceedings of the Fourth Conference on Cutaneous Toxicity, Washington, DC, May 9-11, 1979, reviews agents in the workplace known to cause skin cancer, defines individuals at high risk for various reasons, discusses the importance of uncovering the major etiological factors, and offers suggestions on how this might be accomplished. Types of skin tumors associated with ultraviolet light exposure include solar keratoses, keratoacanthomas, basal cell epitheliomas, squamous cell epitheliomas, and melanomas. Those at risk include people who work outdoors and employees exposed to artificial ultraviolet irradiation sources. Studies have indicated that characteristics of persons at higher risk of developing skin cancer include fair complexion, blonde or red hair, and light eye color; northern European ancestry; those experiencing prolonged erythema; inherited light-sensitive disorders; and acquired photosensitivity or pigment loss. Types of skin tumors associated with polycyclic hydrocarbon exposure include scrotal squamous cell carcinomas. Those at risk for polycyclic hydrocarbon-induced tumors are workers exposed to paraffins, waxes, shale and mineral oils, coal tar, pitch, asphalt, crude oil, and automobile exhaust fumes. These workers include carpenters, diesel engine engineers, farmers, miners, and pavers. Histologic forms of skin changes associated with arsenic include sole and palm keratoses, Bowen's disease, squamous cell carcinoma, and basal cell epitheliomas. Those at risk include painters, dye makers, petroleum refinery workers, copper smelters, and leather workers. Skin cancers induced by ionizing radiation include squamous cell carcinomas, basal cell epitheliomas, and, rarely, sarcomas and melanomas. Those at risk include workers involved in radioactive ore extraction and refining, workers in atomic energy installations, medical and dental personnel, and research biologists. Miscellaneous chemical factors associated with skin cancer include nitrosamines, naphthenic mineral oils, and optical brighteners. Physical factors include prolonged exposure to heat and chronic inflammatory conditions such as discoid lupus erythematosus and the chronic draining sinuses of osteomyelitis. The author concludes that the use of morbidity registries for the handling of such data, including other possible risk factors such as genetic background and nutritional status, could be of great importance in detecting and defining the multiple etiologic factors in skin cancer.
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Secondary Prevention of Skin Cancer in Australia Source: in Primary and Secondary Prevention of Malignant Melanoma. MacKie, R.M. ed. New York, NY, Karger, Pigment Cell, Volume 11, pp. 31-42, 1996.
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Contact: S. Karger AG, 26 West Avon Road, P.O. Box 529, Farmington, CT 06085. (800) 828-5479; (860) 675-7834. Summary: Secondary Prevention of Skin Cancer in Australia, a book chapter in Primary and Secondary Prevention of Malignant Melanoma, discusses activities in Australia aimed at reducing skin cancer, especially melanoma. Australia has the highest incidence of skin cancer in the world. The New South Wales State Cancer Council is well funded and in the past 10 years it has targeted for early diagnosis programs (1) the general public, (2) general practitioners, (3) rural general practitioners, (4) schools, (5) local councils, (6) the workplace, and (7) community groups. Their biggest success is the socalled battle stations, or tents set up on beaches and at swimming pools around Sydney to increase awareness of skin cancer and promote physician visits. Other activities include (1) the Anti-Cancer Council of Victoria; (2) the Queensland Cancer Fund; (3) South Australian Anti-Cancer Foundation; (4) Cancer Foundation of Western Australia; (5) Tasmanian, Australian Capital Territory and Northern Territory Anti-Cancer Foundation; (6) Melanoma Foundation of the University of Sydney; (7) Hunter Melanoma Foundation; (8) Skin and Cancer Foundations; (9) Royal Australian College of Dermatologists; and (10) State Health Departments. Australian studies have shown the need to continue and expand secondary prevention programs. This review shows that Australia has the most active intervention programs for early skin cancer detection in the world. As a result, the cure rate for melanoma in Australia now exceeds 80 percent, and the median tumor thickness has fallen dramatically in the past 20 years. However, the sunny climate and outdoor lifestyle mean that there is a continued need for expansion of secondary prevention efforts in Australia. •
Melanoma of the Skin Source: in Pennsylvania Cancer Incidence and Mortality: 1994-1998. Harrisburg, PA, Pennsylvania Department of Health, pp. 92-99, June 2001. Contact: Pennsylvania Department of Health, Bureau of Health Statistics, 555 Walnut Street, 6th Floor, Harrisburg, PA 17101. (717) 783-2548. INTERNET/EMAIL: www.health.state.pa.us/stats/. Summary: Melanoma of the Skin, a chapter in Pennsylvania Cancer Incidence and Mortality, 1994-1998, presents skin melanoma incidence and mortality data for Pennsylvania (PA) residents from 1989 through 1998, stratified by race, sex, and county. From 1994 through 1998, average annual age-adjusted incidence rates for melanoma of the skin among white males and females were 15.0 and 9.5 cases per 100,000, respectively, much higher than among black males and females, 0.7 case/100,000. There were 2,149 cases of cutaneous melanoma diagnosed in 1998 among PA residents. This represents the largest number of cases reported during the period 1989 through 1998 and is an increase of nearly 90 percent from the number of cases (1,132) reported in 1989. Annual age-adjusted melanoma incidence rates for white males and females have been increasing, a situation paralleled by data for the United States as a whole. The average annual age-adjusted melanoma mortality rates for 1994 through 1998 were much higher for whites, especially males. There were 402 deaths from skin melanoma among PA residents in 1998, the highest annual number recorded from 1989 through 1998. There were no discernible trends in the annual age-adjusted death rates for white males and females from 1989 through 1998. Nearly 91 percent of melanoma cases reported in 1998 were diagnosed during the in situ and local stages of disease. The chapter also summarizes risk factors and American Cancer Society recommendations for the early detection of skin melanoma.
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Who Gets Melanoma and Why Source: in Melanoma: Prevention, Detection, and Treatment. Poole, C. Guerry, D., IV. New Haven, CT, Yale University Press, pp. 21-36, 1998. Contact: Yale University Press, 92A Yale Station, New Haven, CT 06520. (203) 432-0960. Summary: Who Gets Melanoma and Why, a chapter in Melanoma: Prevention, Detection, and Treatment, presents information on the risks for and epidemiology of melanoma. Epidemiologists have pinpointed certain characteristics that, whether they occur separately or in conjunction, predict who is likely to get melanoma. These include (1) a sun-sensitive skin type that may freckle easily, (2) a history of spending too much time in the sun, (3) many common moles or any dysplastic moles, (4) a personal or family history of any of the common kinds of skin cancer (squamous or basal cell carcinoma), and (5) a personal or family history of melanoma. Other less important yet still influential factors include the person's gender, geographical location, and age. The risk associated with each risk factor itself is not great; however, individuals who possess multiple melanoma risk factors may be at dramatically increased risk. The chapter discusses (1) the role of the sun and ultraviolet radiation, (2) the skin types that are susceptible to melanoma, (3) the types of sun exposure that cause melanoma, (4) whether all sun exposure is harmful to most people, (5) what moles are, (6) when a mole should be removed, (7) whether melanoma is hereditary, (8) whether a history of skin cancer is a risk factor for developing melanoma, (9) whether pregnancy is a risk factor for melanoma, (10) whether taking oral contraceptives or undergoing hormone replacement therapy can increase a woman's risk of developing melanoma, and (11) if where a person lives affects whether they might develop melanoma.
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Finding Early Melanoma Source: in Melanoma: Prevention, Detection, and Treatment. Poole, C. Guerry, D., IV. New Haven, CT, Yale University Press, pp. 37-49, 1998. Contact: Yale University Press, 92A Yale Station, New Haven, CT 06520. (203) 432-0960. Summary: Finding Early Melanoma, a chapter in Melanoma: Prevention, Detection, and Treatment, explains that early detection is one of the best lines of defense against melanoma and should be made a top priority in the battle against the disease. It is important to teach the public, primary health care providers, and body care practitioners how to recognize incipient melanoma. Melanoma is always curable when completely removed before it develops the capacity to spread. Regular skin examination is crucial to finding early melanoma at its most curable stage, and it is important for individuals to set up a schedule of self-examinations. Skin examinations should occur in a brightly lighted room. Tools needed include a hand-held flashlight, a full-length mirror, a hand mirror, and two stools or chairs. These tools are necessary for examining every inch of the body. Early melanoma can look like an irregular, inflamed, or spreading flat mole. Many melanomas can change noticeably over weeks or months. Many general practitioners will not conduct a skin examination unless asked, nor do they teach skin self-examination techniques. Most melanomas appear on the backs of people of both sexes, the chests and abdomens of men, and the legs of women. It is important to get any questionable lesions checked, because research has shown that a long lag time between diagnosis and treatment can result in a less favorable prognosis. Health professionals recommend that if people spot a potential melanoma on someone else, they should point it out immediately and recommend treatment. Since 1985, the American Academy of Dermatology has operated a free screening program, and 750,000
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people have received screening. A current dilemma in the field of skin cancer screening is how to reach the individuals at risk and convince them to get their skin checked. •
Future Promise: Prevention of Melanoma Source: in Melanoma: Prevention, Detection, and Treatment. Poole, C. Guerry, D., IV. New Haven, CT, Yale University Press, pp. 98-114, 1998. Contact: Yale University Press, 92A Yale Station, New Haven, CT 06520. (203) 432-0960. Summary: Future Promise: Prevention of Melanoma, a chapter in Melanoma: Prevention, Detection, and Treatment, explores how to change attitudes about sun exposure and work to prevent melanoma. In the United States, large segments of the population know nothing about what melanoma is or what causes it, so they lack the motivation to try to prevent it. In Australia, most individuals know about melanoma because of the extremely high incidence of the disease in their country and the nationwide SunSmart campaign. The Centers for Disease Control and Prevention has given the American Academy of Dermatology funding to follow Australia's lead in providing a comprehensive educational program to spread the message that sun protection saves lives. Parents should learn about protecting their children before their children are born, and they can set an example early on for their children by taking appropriate precautions. Educational efforts in school are also important because they can teach children to play in the shade, wear hats, and put on sunscreen. There should be sun-safe policies for summer camps, where children are typically exposed to a great deal of sun. Adolescents are the least likely group to protect themselves against the sun and most likely to suffer from overexposure. A priority in Australia's program is to help change young adults' attitudes about sun behavior. The melanoma mortality rate for men is higher than it is for women, mainly because many men delay seeking a doctor's advice and are likely to ignore it. There needs to be a profound cultural shift in attitudes about the sun. This may mean getting certain powerful groups involved, including the media and the sports industry (which has been effective in Australia). Because of chlorofluorocarbons in the atmosphere, there are holes in the ozone layer that increase people's exposure to ultraviolet (UV) radiation. The situation will slowly improve as the ozone layer heals itself following decreased use of chlorofluorocarbons. Although natural tanning acts as a weak sunblock and may provide some protection from melanoma, physicians are quick to point out that sun exposure damages the skin. Both UV-A and UV-B are dangerous to the skin, and sunscreens that protect against both are important. Prevention specialists feel that sunscreens should be used only as an adjunct to habits capitalizing on natural sun protection. Following the guidelines for sunscreen use and application is essential. Generously applying a broad-spectrum sunscreen is important, as is following the UV index forecast to avoid sunlight during peak hours.
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Attitudes and Behaviour Towards Sun Exposure: Implications for Melanoma Prevention Source: in Epidemiology, Causes and Prevention of Skin Diseases. Grob, J.J. Stern, R.S. MacKie, R.M. Weinstock, W.A. eds. Oxford, England, Blackwell Science Ltd., pp. 144151, 1997. Contact: Blackwell Science, Inc., Commerce Place, 350 Main Street, Malden, MA 021485018. (800) 759-6102; (617) 388-8250. FAX: (617) 388-8255. Summary: Attitudes and Behaviour Towards Sun Exposure: Implications for Melanoma Prevention, a chapter in Epidemiology, Causes and Prevention of Skin Diseases, considers the knowledge, attitudes, and behavior towards sun exposure in developed
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countries. Sun behavior and practice of protective measures differ widely from country to country. Any dermatologist dedicated to primary prevention must bear several facts in mind. First, it is difficult to extrapolate data from one country to another. Tanning is a social phenomenon, and the risk of melanoma creates a psychological conflict between the desire to be tanned and the dangers of sun exposure. Awareness of one's sun sensitivity is a determinant. Use of sunscreen is also a social phenomenon. There is a gap between what people know, what they intend to do, and what they do. Objective evaluation of primary melanoma prevention campaigns is difficult. Prevention campaigning is resource intensive. Many melanoma prevention campaigns have been successfully conducted in schools. An interaction between primary prevention and screening campaigns is inevitable. Campaigns aimed at primary melanoma prevention by reducing sun exposure are hindered by uncertainties involving the most suitable message, the most effective means of delivery, the actual impact on behavior, the durability of changes, and the difficulty of measuring long-term effects. Experience indicates that, although interesting results hav e been obtained in countries that have applied intense resources, outcome depends on psychosocial factors. •
Lack of Efficacy of Common Sunscreens in Melanoma Prevention Source: in Epidemiology, Causes and Prevention of Skin Diseases. Grob, J.J. Stern, R.S. MacKie, R.M. Weinstock, W.A. eds. Oxford, England, Blackwell Science Ltd., pp. 151159, 1997. Contact: Blackwell Science, Inc., Commerce Place, 350 Main Street, Malden, MA 021485018. (800) 759-6102; (617) 388-8250. FAX: (617) 388-8255. Summary: Lack of Efficacy of Common Sunscreens in Melanoma Prevention, a chapter in Epidemiology, Causes and Prevention of Skin Diseases, discusses the incidence of malignant melanoma in the United States, which has increased faster than any other cancer during the past 3 decades. Worldwide, the countries where chemical sunscreens have been widely promoted and adopted have experienced the greatest rise in cutaneous melanoma, with a rise in death rates following the acceleration in incidence rates by 5 to 10 years. Experimental studies of sunscreens mainly have used artificial sources of irradiation designed to maximize ultraviolet B exposures. Analysis of the absorption spectrum of the sunscreen ingredient PABA revealed that it absorbed ultraviolet B, but provided no absorption in the ultraviolet A range. Three epidemiological studies found significantly higher risk of melanoma associated with sunscreen use in both sexes combined. Two others reported significantly elevated odds ratios associated with use of sunscreens in men and no favorable association with sunscreen use in women. One study reported a higher risk of basal cell carcinoma in women who used sunscreens, compared to nonusers among women spending over 8 hours outdoors. The findings help to explain some of the paradoxes in the epidemiology of melanoma, particularly its stronger association with skin pigmentation than with latitude. Mortality rates for skin malignancies in the United States did not rise immediately after introduction of sunscreens, but rather after an appropriate latency period. For most individuals, moderate year-round exposure to the sun is desirable to stimulate accommodation and protective pigmentation, as well as for adequate synthesis of vitamin D in the skin. Traditional measures for reducing solar overexposure, such as wearing of hats and clothing, would continue to be appropriate for those with unaccommodated skin who must remain in the sun for extended periods.
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Role of Sunscreen Lotions in Melanoma Prevention Source: in Epidemiology, Causes and Prevention of Skin Diseases. Grob, J.J. Stern, R.S. MacKie, R.M. Weinstock, W.A. eds. Oxford, England, Blackwell Science Ltd., pp. 159163, 1997. Contact: Blackwell Science, Inc., Commerce Place, 350 Main Street, Malden, MA 021485018. (800) 759-6102; (617) 388-8250. FAX: (617) 388-8255. Summary: Role of Sunscreen Lotions in Melanoma Prevention, a chapter in Epidemiology, Causes and Prevention of Skin Diseases, notes that using sunscreens has not yet been established to be beneficial, and the problem may indeed be more complex than is generally appreciated. Persons using sunscreen may compensate for sunscreen use by increasing their time in the sun or decreasing the use of protective clothing. Sunscreen use may increase the intermittency of ultraviolet exposure to the skin, which could adversely affect melanoma risk. Present evidence suggests that sunscreens are effective for prevention of melanoma, but several areas of uncertainty must be resolved before this conclusion can be considered established. It would therefore be prudent to recommend to the general public that (1) sunscreens not be used to increase exposure to the sun, (2) consistent use is preferable, and (3) broad spectrum sunscreens are preferable to those that primarily protect against the ultraviolet B portion of the spectrum.
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Screening for Melanoma: Methods, Advantages and Limits Source: in Epidemiology, Causes and Prevention of Skin Diseases. Grob, J.J. Stern, R.S. MacKie, R.M. Weinstock, W.A. eds. Oxford, England, Blackwell Science Ltd., pp. 166173, 1997. Contact: Blackwell Science, Inc., Commerce Place, 350 Main Street, Malden, MA 021485018. (800) 759-6102; (617) 388-8250. FAX: (617)388-8255. Summary: Screening for Melanoma: Methods, Advantages and Limits, a chapter in Epidemiology, Causes and Prevention of Skin Diseases, notes that in recent years public health bodies and the medical profession have been contemplating and initiating educational programs directed at primary prevention and early detection. Screening programs for skin cancer and melanoma are increasing in number. To effectively develop a screening program, certain conditions must be met: (1) The condition sought should be an important health problem; (2) there should be an accepted treatment for patients with recognized disease; (3) facilities for diagnosis and treatment should be available; (4) there should be a recognizable latent or early symptomatic stage; (5) there should be a suitable test or examination; (6) the test should be acceptable to the population; (7) the natural history of the condition, including development from latent to declared disease, should be adequately understood; (8) the cost of screening, including diagnosis and treatment of positive screens, should be economically balanced in relation to possible expenditures on medical care as a whole; and (9) screening should be a continuing process and not a single occasion project. There are several screening procedures for skin cancer and melanoma. Targeting high-risk persons should enhance the efficiency of the process. Volunteer screening campaigns may reach only a small section of the population. The key components of the successful screening intervention include (1) an organizational forum fo r program development, (2) an intensive precampaign public education program, (3) dedicated personnel, (4) suitable locations, (5) narrowing the scope of the screen by focusing on melanoma only, (6) understanding that complete skin examinations are time-consuming and unproductive, (7) rigorous
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followup of positive screens, (8) use of overall outcome measures, and (9) assessment of actual and hidden costs. •
Causes for the Delay in Diagnosis of Melanoma Source: in Epidemiology, Causes and Prevention of Skin Diseases. Grob, J.J. Stern, R.S. MacKie, R.M. Weinstock, W.A. eds. Oxford, England, Blackwell Science Ltd., pp. 177183, 1997. Contact: Blackwell Science, Inc., Commerce Place, 350 Main Street, Malden, MA 021485018. (800) 759-6102; (617) 388-8250. FAX: (617) 388-8255. Summary: Causes for the Delay in Diagnosis of Melanoma, a chapter in Epidemiology, Causes and Prevention of Skin Diseases, indicates that the delay in diagnosis may be in the order of 1 year. If the goal of early melanoma detection is to be achieved, it is critical that the factors that cause a delay in the diagnosis be understood so that appropriate interventions are instituted. In order to understand the reason for the delay in diagnosis, several questions must be addressed, including (1) who makes the diagnosis, (2) who is able to make the diagnosis, (3) why the delay, and (4) was it caused by the patient or physician or both. Identification of the person who detects, or fails to detect, melanoma is important if we are to decrease the time to diagnosis and to organize educational efforts optimally. The ability of a physician to accurately diagnose or suspect melanoma in a patient and perform a biopsy/excision or make a timely referral is a critical factor in improving the time to diagnosis. A lower diagnostic accuracy revealed by nondermatologists in studies indicates a need for improved professional education, given the increasing role of the primary caregiver in the initial assessment of the patient in the United States and their already-prominent role in other countries. Given the importance of early diagnosis, and the difficulties in clinical diagnosis, even among skin cancer specialists with extensive experience, there has been on-going research into clinical techniques that may improve diagnostic accuracy.
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Primary Prevention Activities for Malignant Melanoma in the United States Source: in Primary and Secondary Prevention of Malignant Melanoma. MacKie, R.M. ed. Farmington, CT, Karger, Pigment Cell, pp. 43-73, 1996. Contact: S. Karger AG, 26 West Avon Road, P.O. Box 529, Farmington, CT 06085. (800) 828-5479. Summary: Primary Prevention Activities for Malignant Melanoma in the United States points out that the United States lags behind other countries with well established educational efforts regarding melanoma dangers. Yet the United States also has a high incidence of melanoma (an expected 34,000 new cases of melanoma diagnosed in 1995). This chapter examines (1) the difference between the United States population and the rest of the world (motivation, knowledge base, and access to health care may be more of a problem in the United States than in other countries); (2) theoretical models of public education for melanoma prevention (social learning models, stages of change model); and (3) past and ongoing efforts of primary prevention in the United States (through national programs, the American Academy of Dermatology, the American Cancer Society, and local programs such as those in Arizona, M.D. Anderson Cancer Center in Houston, University of California, San Francisco, and the Moffitt Cancer Center in Florida). Other topics include chemoprevention trials in the United States, whether programs for the primary and secondary prevention of melanoma in the United States are effective, and future initiatives. Melanoma and skin cancer should be amenable to a multidisciplinary approach for cancer control. Efforts should acknowledge trends in
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skin cancer by gender, age, and social class; for example, the highest mortality rates for melanoma in the U.S. are in older men, especially white men over 50 years. Prevention and control efforts will need to focus on that group as well as on those of lower social class. A combination of primary prevention, early detection, and education tailored to the local or state health care system and level of risk of the population served should decrease the rising melanoma and skin cancer incidence and mortality rates in the United States. •
Role of Atypical Mole Syndrome and Cutaneous Naevi in the Development of Melanoma Source: in Skin Cancer. Leigh, I.M. Newton Bishop, J.A. Kripke, M.L., eds. Plainview, NY, Cold Spring Harbor Laboratory Press, pp. 237-249, 1996. Contact: Cold Spring Harbor Laboratory Press, 10 Skyline Drive, Plainview, NY 118039729. (800) 843-4388. FAX: (516) 349-1946. INTERNET/EMAIL: www.cshl.org.
[email protected]. Summary: The Role of Atypical Mole Syndrome and Cutaneous Naevi in the Development of Melanoma, a chapter in Skin Cancer, discusses melanocyte nevi and atypical or dysplastic nevi as risk factors for melanoma. The chapter discusses (1) nevi and melanoma risk; (2) genetic susceptibility to melanoma and nevi; (3) genetic studies of families at high risk for melanoma; (4) ocular melanoma and nevi; and (5) nongenetic causes of nevi, including ultraviolet radiation exposure and chemotherapy for other malignancies. Epidemiological studies have shown that the density of common melanocytic nevi and the presence of atypical nevi (the atypical mole syndrome (AMS) phenotype) are both major risk factors for melanoma. These associations hold for both cutaneous and ocular melanoma. Twin and family-based studies indicate that nevus density has a strong inherited component, which is probably due to several interacting genes rather than a single gene. Comparison studies in various countries suggest that nevus densities are also related to sun exposure, but the results are rather equivocal, and further studies are required. Germline mutations in the CDKN2 tumor suppressor gene on chromosome 9p, which have been found in some families with a high risk of melanoma, also appear to be associated with an increased nevus density. Nevus density and the AMS may be potentially useful phenotypes for identifying melanoma susceptibility genes through linkage or association studies. In the meantime, these phenotypes taken together with other known risk factors such as hair, eye, and skin color, freckling, and family history provide a good basis for identifying individuals at high risk of melanoma.
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Screening for Melanoma Source: in Advances in Cancer Screening. Miller, A.B. ed. Boston, MA. Kluwer Academic Publishers, pp. 129-147, 1996. Contact: Kluwer Academic Publishers, 101 Philip Drive, Assinippi Park, Norwell, MA 02061. Summary: Screening for Melanoma, a chapter in Advances in Cancer Screening, discusses melanoma research since 1990, focusing on (1) trends, (2) recommendations for screening, (3) current use of screening, (4) data on the performance of screening, and (5) further research. Melanoma incidence and mortality have been increasing in most countries for several decades. Melanoma screening is being recommended in many countries. In the United States, the American Cancer Society and the American Academy of Dermatology recommend regular physician skin examination and self-
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screening. The Canadian Task Force on the Periodic Health Examination and the United States Preventive Services Task Force do not recommend skin screening of the general population, but do recommend screening for high-risk groups. In 1992, the National Institutes of Health Consensus Development Conference on Early Melanoma concluded that there is enough evidence to warrant screening programs in the United States. The potential benefit of screening is based on the large variation in melanoma survival rate. Five-year survival rates range from 47 to 96 percent with smaller skin lesions. The costs of, and health service demands regarding melanoma screening are considerable. A major problem in melanoma screening is that the performance characteristics of proposed physician screening or self-screening examinations are still unknown. The author concludes that systematic melanoma screening of the general population is not presently recommended, but there is evidence of its potential effectiveness. Further research should focus on the evaluation of screening methods for melanoma in the general population. •
Melanoma Control in the United States: Current Status Source: in Skin Cancer: Basic Science, Clinical Research and Treatment. Garbe, C. Schmitz, S. Orfanos, C.E. eds. New York, Springer-Verlag, Recent Results in Cancer Research, Vol. 139, pp. 215-224, 1995. Contact: Springer-Verlag, 175 Fifth Avenue, New York, NY 10010. Summary: Melanoma Control in the United States: Current Status, a book chapter in Skin Cancer: Basic Science, Clinical Research and Treatment, reviews and summarizes ongoing melanoma control activities in the United States, including prevention, education, and early detection and screening. The ideal measure of the success of a melanoma control program should come from a randomized trial demonstrating a sustained reduction in the mortality rates of melanoma in a defined population. Because such trials have formidable logistical challenges, no such trial exists. Alternatively, tracking intermediate or short-term outcome measures in interventions outside of a randomized trial may serve as an indicator of future progress. Such outcome measures may include (1) increased sales of sunscreens and protective clothing, (2) decreased rates of sunbathing, (3) decreased rates of sunburn, and (4) increased self-reported use of sunscreens and protective clothing. In the United States, skin cancer education primarily occurs during the spring, when local media publicize skin cancer screening programs and disseminate education messages. In a recent nationally-representative sample of 502 white Americans, awareness of skin cancer was relatively high and the major risk factors were widely known. Annual free skin cancer screening programs have provided skin examinations by dermatologists to more than 600,000 Americans. Screening programs deliver education through three means: (1) Prescreening publicity disseminates the availability of screening and publicizes melanoma risk factors, (2) screening sessions provide participants with educational literature and offer an opportunity for the physician to provide skin cancer prevention counseling, and (3) after screening, participants are provided with essential information on the importance of followup. In the future, multiple strategies, including both education and screening, will be needed to combat the increasing incidence and mortality rates of skin cancer. 34 references.
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Diagnosis of Melanoma Source: in Melanoma: Diagnosis and Treatment. Elaimy, W.M. Coleman, W.P. Krementz, E.T. eds. New Orleans, LA, Louisiana Cancer Consortium, pp. 23-33, 1994.
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Contact: Louisiana Cancer Consortium, 1430 Tulane Avenue, New Orleans, LA 70112. (504) 588-5518. Summary: Diagnosis of Melanoma, a chapter in Melanoma: Diagnosis and Treatment, discusses the clinical features of early melanoma, the features of other malignant or benign lesions, and the steps physicians should take when seeing a patient who might have melanoma. Visual indications of melanoma include change in size, shape, or color of an existing lesion. Altered sensation of the lesion, such as mild itching or tingling, can be an early symptom of melanoma. Bleeding usually occurs in more advanced lesions. The physician should take a relevant family and patient history of melanoma or dysplastic nevi and note the physical characteristics of any suspicious lesions while performing a careful physical examination under a good light and with a magnifying lens, if possible. The physician should record the location of the melanoma and measure the largest diameter of the lesion. Also, the physician should evaluate the border for irregular outline or asymmetry, note the color, and document the patient's skin type and degree of sun damage. The physician should recognize the major growth patterns of melanoma and examine the individual lesion by considering these lesion types: Superficial spreading pagetoid melanoma, nodular melanoma, lentigo malignant melanoma, and acral-lentiginous melanoma. Benign pigmented lesions usually show order in color, symmetry of border, and uniformity of surface characteristics. These lesions include melanocytic nevi, dysplastic nevus, blue nevi, seborrheic keratoses, hemangiomas, cutaneous tags or polyps, and pigmented basal cell carcinoma. The preferred method of biopsy involves excising a suspected lesion for diagnosis. The excision will allow the pathologist to use the entire specimen for diagnosis and to evaluate tumor thickness and depth of invasion. The field generally accepts that incisional biopsy does not negatively affect the spread of melanoma. The physician should perform proper surgical treatment soon after establishing the diagnosis of melanoma. •
Malignant Melanoma: Prevention Source: in Melanoma: Diagnosis and Treatment. Elaimy, W.M. Coleman, W.P. Krementz, E.T. eds. New Orleans, LA, Louisiana Cancer Consortium, pp. 57-60, 1994. Contact: Louisiana Cancer Consortium, 1430 Tulane Avenue, New Orleans, LA 70112. (504) 588-5518. Summary: Malignant Melanoma: Prevention, a chapter in Melanoma: Diagnosis and Treatment, discusses how people can protect themselves against the premature aging and skin cancer (including melanoma) that sun exposure can cause. Proper protection from the damaging rays of the sun includes avoidance of unnecessary sun exposure, wearing protective clothing, and application of effective sunscreens (at least a sun protection factor (SPF) of 15). Other important prevention methods involve skin selfexamination and the identification and screening of patients at risk for melanoma. People should especially avoid sun exposure between 10:00 a.m. and 2:00 p.m., the peak hours of harmful ultraviolet (UV) radiation. The radiant lights used in tanning booths also contain UV radiation. Certain medications can increase sun sensitivity. Therefore, people should consult their physicians before going out into the sun when they are taking medications. People should also know that surfaces such as snow, sand, water, and concrete can reflect more than 50 percent of the sun's rays. Studies show that the routine use of sunscreens before age 18 can reduce skin cancer by 78 percent. Education about the sun should begin as early as possible, because UV light damage accumulates. Clothing also acts as a kind of sunscreen; in addition to lotions, people should use protective clothing such as broad-rimmed hats and UV-opaque sunglasses. A
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dermatologist has suggested the phrase Declare WAR on Sunlight, by (1) wearing protective clothing, (2) applying sunscreens, and (3) refraining from unnecessary exposure to the sun. Screening can reduce the number of melanomas and deaths due to melanomas by finding the disease and effectively treating it as early as possible. Visual examination can accurately detect melanoma; the American Academy of Dermatology has established guidelines for differentiating cancerous from noncancerous lesions. Routine self-examination is a tool that gives people the opportunity to recognize early malignant melanoma when it can still be cured. •
Early Detection and Lethal Melanoma in Connecticut: A Preliminary Analysis Source: in Epidemiologic Aspects of Cutaneous Malignant Melanoma. Gallagher, R.P. Elwood, J.M. eds. Norwell, MA, Kluwer Academic Publishers, pp. 265-271, 1994. Contact: Kluwer Academic Publishers, 101 Philip Drive, Assinippi Park, Norwell, MA 02061. Summary: Early Detection and Lethal Melanoma in Connecticut: A Preliminary Analysis, a book chapter in Epidemiologic Aspects of Cutaneous Malignant Melanoma, examines a study that investigated (1) whether early detection through skin awareness and skin self-examination would protect one from dying from melanoma and (2) the relationship of skin examination to stage at diagnosis of melanoma. The study subjects consisted of 884 Connecticut residents with a primary cutaneous melanoma diagnosed between January 1987 and May 1989 and 573 controls selected from the general population through random-digit dialing. All incident cases of melanoma were ascertained through bi-weekly review of pathology logs of 35 hospitals and four freestanding dermopathology laboratories in Connecticut. A questionnaire addressed (1) basic demographics, (2) familial history of skin cancer, (3) pigmentary characteristics, (4) health and reproductive histories, and (5) potential confounding factors such as recreational and occupational sun exposure. Nevi on the backs and arms of subjects were counted by trained nurse-interviewers. A sun exposure score was created based on the amount of time spent in outdoor recreation and vacations at sunnier spots than the residence of the respondent. Analysis by sex, age, and melanoma depth at diagnosis showed that there was no difference in participation by sex or age, but that those diagnosed with deeper lesions were more likely to decline participation. The effect of this differential participation would be to bias estimates of risk toward the null as there appears to be an inverse trend of screening behavior with lesion depth. Final conclusions cannot be drawn from these data in spite of encouraging preliminary results that screening reduces mortality from melanoma.
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Early Diagnostic Approaches for Human Melanoma Source: in Malignant Melanomas: Advances in Treatment. Leong, S.P.L., ed. Georgetown, TX, R.G. Landes Company, pages 18-27, 1992. Contact: CRC Press, 2000 Corporate Boulevard, NW., Boca Raton, FL 33431. (407) 9940555. Summary: Early Diagnostic Approaches for Human Melanoma, a book chapter in Malignant Melanomas: Advances in Treatment, discusses early detection of melanoma and other types of pigmented lesions. When a melanoma is detected at a thickness of less than 0.76 mm, 5-year survival rate ranges from 93-100 percent in different centers. If it is not detected until thickness is over 4 mm, the 5-year survival rate is reduced to 3067 percent. The general public and individual patients can be taught the American Cancer Society (ACS) ABCD's for skin cancer detection, which include asymmetry,
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border irregularity, color irregularity, and diameter greater than 6 mm of pigmented lesions. Not all pigmented lesions that meet the ABCD criteria will prove to be melanoma; other diagnoses could include seborrheic keratoses, pigmented basal cell carcinomas, and subungual hematomas. Studies have shown that nondermatologists are less able than dermatologists to diagnose melanoma and other types of pigmented lesions, but even experienced dermatologists do not have 100 percent accuracy when clinically assessing melanoma. New tools and technologies may enhance the diagnostician's abilities (e.g., epiluminescence microscopy and computer imaging). The technique of epiluminescence microscopy combines the benefits of magnification and application of oil to the lesion to give a more accurate clinical diagnosis before resorting to biopsy. Diagnoses with epiluminescent microscopy outperformed routine clinical diagnosis in one study, with diagnostic accuracy of 85 percent compared to 61 percent. Computer imaging can help objectify the somewhat subjective impressions used by clinicians in deciding whether or not a lesion is suspicious for melanoma. Most melanomas can be cured, when they are still thin, by simple excision surgery. New and old techniques for early recognition of melanoma can save many years of life and prevent substantial morbidity and mortality. 8 figures, 2 tables, 24 references. •
Early Detection of Malignant Melanoma: The Role of Physician Examination and Self-Examination of the Skin Source: in Cancer of the Skin. Friedman, R.J. Rigel, D.S. Kopf, A.W. Harris, M.N. Baker, D. Philadelphia, PA, W.B. Saunders Company, pages 117-124, 1991. Contact: W.B. Saunders Company, The Curtis Center, Independence Square West, Philadelphia, PA 19106. Summary: Early Detection of Malignant Melanoma: The Role of Physician Examination and Self-Examination of the Skin, a book chapter in Cancer of the Skin, states that the combination of routine physician examination of the skin and self-examination provides a realistic opportunity for the identification of early malignant melanomas. Section one addresses the importance of early diagnosis. Section two, Basic Factors in Early Diagnosis, discusses (1) common benign pigmented lesions (i.e., simple lentigo, junctional nevus, compound nevus, intradermal nevus, solar lentigo, and seborrheic keratosis); (2) age as a factor in onset and diagnosis of pigmented skin lesions; (3) clinical characteristics of early malignant melanoma; and (4) precursor lesions of malignant melanoma. Section three, Examination of the Skin: The First Step Toward Diagnosis, addresses self-examination and physician examination of the skin. To make an early diagnosis, the physician must have a high index of suspicion for malignant melanoma and thorough knowledge of the (1) clinical characteristics of early malignant melanomas; (2) clinical features of the common types of pigmented lesions that must be differentiated from malignant melanomas; (3) the characteristics of precursor lesions that may give rise to malignant melanomas; and (4) other factors that increase the risk of developing a malignant melanoma, e.g., familial history of the disease, many melanocytic nevi, excessive sun exposure, light complexion, history of sunburns, and susceptible age. Removal of thin lesions can significantly reduce the mortality from this potentially serious form of cutaneous cancer.
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Screening and Early Diagnosis for Melanoma in Australia and New Zealand Source: in Cancer Screening. Miller, A.B. Chamberlain, J. Day, N.E. Hakama, M. Prorok, P.C. eds. Cambridge, England, Cambridge University Press, pp. 243-256, 1991.
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Contact: Press Syndicate of the University of Cambridge, 40 West 20th Street, New York, NY 10011-4211. Summary: Screening and Early Diagnosis for Melanoma in Australia and New Zealand, a chapter in Cancer Screening, indicates there is no major program in these countries that could be described accurately as a screening program, but that the use of selfassessment for lesions that may be early melanoma or suspicious moles is being encouraged by public education campaigns. The lifetime risk of developing melanoma is estimated to be 1 in 55 in Australia, compared to 1 in 1.5 for non-melanoma skin cancer. Certain specific television programs have appeared to have the most impact on early detection. One particular documentary featured a young patient dying from melanoma. The program aired on a peak time current affairs program and produced a major reaction, with great increases in referrals for melanoma in subsequent weeks. A second showing of the program had similar results. In New Zealand, the main focus of activity has been the educational campaigns run for the public by the Cancer Society of New Zealand, using television, radio and magazine advertising, and publicity material sent to doctors, pharmacies, and schools. The Minister of Health in New Zealand has specified 10 health targets to be the focus of the actions of area health boards over the next few years. The options for screening include the general population screening by professionals, identification of precursor lesions, and identification of high-risk participants. Currently, screening programs can not be recommended for melanoma on a general population basis, primarily because the specific tests to be used have not been defined, and their validity and performance characteristics have not been assessed. On the basis of its overall frequency, seriousness, and the evidence that chronologically earlier diagnosis is likely to result in considerably improved survival, melanoma can be considered a prime candidate for screening and early diagnosis programs. This suggests there is a high research priority to develop and validate particular tests for early diagnosis of melanoma, and for the identification of high-risk participants who might benefit from organized surveillance. •
Screening for Melanoma in the UK Source: in Cancer Screening. Miller, A.B. Chamberlain, J. Day, N.E. Hakama, M. Prorok, P.C. eds. Cambridge, England, Cambridge University Press, pp. 257-266, 1991. Contact: Press Syndicate of the University of Cambridge, 40 West 20th Street, New York, NY 10011-4211. Summary: Screening for Melanoma in the UK, a chapter in Cancer Screening, discusses (1) strategies for reducing melanoma mortality, (2) health education campaigns and pigmented lesion clinics in the United Kingdom (UK), (3) the Glasgow Campaign, (4) the Cancer Research Campaign (CRC), (5) population-based analysis, (6) mortality data, (7) pathological definition and consistency, (8) published findings from the CRC campaign centers, and (9) economic aspects of the program. Undoubtedly, the Glasgow and CRC campaigns were effective in making the public more aware of the risk of melanoma and prompting referral. However, it is important that the effort be examined for a true benefit in terms of reduced mortality or morbidity, since there is as yet no evidence from any other studies that mortality or the incidence of advanced melanoma are significantly reduced by such campaigns. Whether or not further deliberate education campaigns are mounted, general practitioners and dermatologists are likely to face increasing demands for attention to pigmented lesions. Research must therefore also be directed toward enabling general practitioners to reduce the number of unnecessary referrals, and towards reducing the costs of outpatient investigations by
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controlling biopsy rates and perhaps by employing nurse specialists to sort out and reassure those who can safely be discharged without seeing the dermatologist. •
Evaluating the Efficacy of Skin Self-Exam and Other Surveillance Measures in Persons at Various Levels of Risk for Cutaneous Malignant Melanoma: An Ongoing Case-Control Study Source: in Advances in Cancer Control: Innovations and Research. Proceedings of the Sixth Annual Meeting on Advances in Cancer Control: A Combined Meeting of the Association of Community Cancer Centers/Association of American Cancer Institutes, Held in Washington, DC, March 15-16, 1988. Anderson, P.N. Engstrom, P.F. Mortenson, L.E. eds. New York, NY, Alan R. Liss, Inc., pages 297-305, 1989. Contact: Alan R. Liss, Inc., 41 East 11th Street, New York, NY 10003. Summary: Evaluating the Efficacy of Skin Self-Exam and Other Surveillance Measures in Persons at Various Levels of Risk for Cutaneous Malignant Melanoma: An Ongoing Case-Control Study, a book chapter in Advances in Cancer Control: Innovations and Research, report results of an ongoing population-based case-control study. Conducted to test the hypothesis that skin examination reduces mortality from cutaneous melanoma, researchers conducted the study in Connecticut during 1986-1991. Researchers ascertained and interviewed incident cases of melanoma and compared them to a random sample of people without disease, matched for age and sex. Cases with lethal melanoma were identified and compared to the controls with respect to skin examination practices, after adjustment for etiologic factors. Nonlethal invasive melanoma and in-situ melanoma were also compared to the general population in terms of level of surveillance of the skin. To define skin surveillance, researchers videotaped interviews with melanoma patients and healthy controls to determine (1) how they thought about their skin, (2) the language they used in describing their skin and unusual marks, and (3) the ways they examined it. Patients completed a questionnaire measuring the duration and intensity of skin surveillance behavior. Registered Nurse interviewers were trained to assess pigmentary features in both cases and controls. They conducted counts of pigmented lesions on the arms and backs of subjects and assessed hair, skin, and eye color in a standardized way. Pigmented lesions, both benign and malignant, were classified in terms of symptoms and date of onset. To address the role of attentiveness to symptoms or delay in seeking medical intervention, analyses of surveillance behavior was stratified by the subject's knowledge of melanoma signs and his risk factors. Data showed 27 percent of controls reported ever conducting a purposeful examination of regions of their skin. 23 references.
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Programmes for the Primary Prevention of Melanoma in Australia Source: in Primary and Secondary Prevention of Malignant Melanoma. MacKie, R.M. ed. Farmington, CT, Karger, Pigment Cell, Volume 11, pp. 93-110, 1996. Contact: S. Karger AG, 26 West Avon Road, P.O. Box 529, Farmington, CT 06085. (800) 828-5479. Summary: Programmes for the Primary Prevention of Melanoma in Australia, a book chapter in Primary and Secondary Prevention of Malignant Melanoma, reviews the scientific data underlying skin cancer prevention programs in Australia and gives examples of programs and measures of outcomes during the past 20 years. Program development has relied on epidemiologic data which suggest that sunlight is the major environmental risk factor for melanoma in people predisposed to develop it. The primary target has been childhood sun exposure, especially when it causes sunburn; the
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secondary target has been adult exposures that lead to sunburn. Program development has concentrated on promoting natural protection from sunlight, rather than relying on filtering out wavelengths. Such protection includes wearing hats and clothing, avoiding sun exposure during the middle of the day, and seeking shade when outdoors. Public health authorities recommend the selection of sunscreening products, regardless of skin type, but discourage the use of sun exposure times. Australian law requires the reporting of all new cases of invasive melanoma to state cancer registries, so that they can provide accurate incidence and mortality data related to melanoma. An increasing number of organizations in Australia have become involved in melanoma education programs and structural change activities. They have produced resources that teachers can incorporate into existing school curricula. Formal education programs have been supplemented by the advertising of organizations such as sunscreen manufacturers. Structural changes have included the introduction of standards for sunscreens that incorporate the sun protection factor (SPF), tax exemptions for sunscreen products that comply with the Australian standard and have an SPF rating of 4 or more, occupational health and safety programs for those who work outdoors, sunlight protection policies in schools, and legislation to limit the manufacture, distribution, use, and release of ozonedepleting substances. Outcome data have substantiated the effectiveness of education programs and structural changes. More than 90 percent of Australians have heard of melanoma and more than 95 percent believe that skin cancer is a serious disease. Children, adolescents, and young adults have the highest knowledge of the primary prevention programs. The authors conclude that future research could involve developing programs designed to change behavior. •
Methodological Issues in Research on Primary and Secondary Prevention of Malignant Melanoma Source: in Primary and Secondary Prevention of Malignant Melanoma. MacKie, R.M. ed. New York, NY, Karger, Pigment Cell, Volume 11, pp. 1-21, 1996. Contact: S. Karger AG, 26 West Avon Road, P.O. Box 529, Farmington, CT 06085. (800) 828-5479; (860) 675-7834. Summary: Methodological Issues in Research on Primary and Secondary Prevention of Malignant Melanoma, a book chapter in Primary and Secondary Prevention of Malignant Melanoma, focuses on methodological issues involved in measuring and modifying melanoma-related behavior. Melanoma-related behavior is defined as any behavior that increases or decreases the risk of individual or groups developing malignant melanoma or of having it detected and treated early. The different features of primary and secondary prevention behaviors need to be considered when developing methods to influence risk behaviors and to measure the effects of behavior change interventions. The chapter discusses (1) measures of risk (susceptibility, sunburn); (2) measuring ultraviolet (UV) exposure via(on-skin instruments and ambient measures; (3) measuring environmental factors that affect behavior; (4) measuring behaviors that affect UV exposure; (5) problems in the use of self-report data; (6) knowledge questions; (7) beliefs, attitudes, and intentions; (8) proxy data on groups or institutions; (9) weather and season as confounding variables; (10) reliability and validity of measures; (11) formulating programs; (12) applications of behavioral theory; and (13) evaluating specific interventions. Behavioral factors play the dominant role in public health melanoma prevention programs. Wise application of principles derived from behavioral research, clear thinking about and analysis of the behavioral issues involved in prevention, and rigorous measurement of determinants and outcomes will enable programs to be well formulated and tested adequately.
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Secondary Prevention of Malignant Melanoma in Europe Source: in Primary and Secondary Prevention of Malignant Melanoma. MacKie, R.M. ed. New York, NY, Karger, Pigment Cell, Volume 11, pp. 22-30, 1996. Contact: S. Karger AG, 26 West Avon Road, P.O. Box 529, Farmington, CT 06085. (800) 828-5479; (860) 675-7834. Summary: Secondary Prevention of Malignant Melanoma in Europe, a book chapter in Primary and Secondary Prevention of Malignant Melanoma, discusses public education programs about prevention of melanoma developed in some European countries. In Northern Italy, a campaign for early diagnosis for cutaneous malignant melanoma was begun in 1977 and repeated 4 years later; evaluation of melanoma-related deaths has suggested that 22 lives were saved during 1977-1985 because of the program. United Kingdom early diagnosis of skin cancer public education activities began in the west of Scotland in 1985 and showed a good effect on early detection of lesions; following this experience, the United Kingdom Cancer Research Campaign funded seven other public education campaigns to do similar work. A Netherlands early detection of skin cancer public education program cost a fair amount but detected some malignant melanomas. In Austria, a clinic saw 1,054 patients between 1985-91 and detected between 126 and 213 malignant melanomas per year from these patients. In Germany in 1989, immediately after an early detection of skin cancer public education campaign, the number of newly diagnosed cutaneous melanomas rose by 80 percent compared with a year earlier. In Switzerland, a similar campaign saw the number of newly diagnosed cases rise 116 percent at first. It would be of value to introduce some integration into European early detection activities for melanoma early diagnosis, to save duplication of efforts but continue to provide this service.
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Melanoma: Prevention and Early Diagnosis Source: in Cancer Prevention in Primary Care. Austoker, J. London, United Kingdom, BMJ Publishing Group, pp. 60-74, 1995. Summary: The author provides skin cancer facts, risks of melanoma, and early measures to prevent and detect skin cancer. Skin cancer is common across the world and incidence is increasing. Of the three main types of skin cancer, basal cell carcinoma and squamous cell carcinoma occur most frequently, tend to occur in older people, and are over 95 percent curable. Malignant melanoma is relatively rare and accounts for 11 percent of skin cancers. Survival after early detection of melanoma is very good. Risk factors for skin cancer are (1) excessive sun exposure, (2) susceptible skin type, (3) changes in an existing mole, (4) presence of many naevi, (5) and previous melanoma. Protective factors include (1) the use of sunscreens, (2) avoiding strong sunlight, (3) clothing, (4) avoiding tanning beds, and (5) remembering that the effects of sun-induced skin damage are cumulative. The author describes a health promotion campaign in Australia, based on the stages of change model, which suggests that sun exposure can be reduced fairly quickly in an urban population. In the United Kingdom, a public education campaign, Health of the Nation, was designed to reduce skin cancer, increase awareness, and change people's attitudes toward sun exposure. The author suggests that, until research proves that early detection of skin cancer reduces mortality from melanoma, promotion of early detection is not recommended. The emphasis should be on primary prevention. 1 figure, 4 tables, 32 references.
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Malignant Melanoma: The Story Unfolds Source: in Preventing Cancers. Heller, T. Bailey, L. Pattison, S. eds. Buckingham, England, Open University Press, pp. 68-77, 1992. Contact: Open University Press, 1900 Frost Road, Suite 101, Bristol, PA 19007. Summary: Malignant Melanoma, a chapter in Preventing Cancers, discusses the epidemiology of cutaneous malignant melanoma in Europe, the phenotypic characteristics of the melanoma patient, what triggers malignant melanoma along with when and why it is triggered, changes in habits leading to greater sun exposure, and steps that can be taken to reduce the death rate form malignant melanoma. The most extensive epidemiological studies on the subject have been carried out in Scandinavia, Germany, and Great Britain. In the 1960s and 1970s, the link was drawn between the incidence of melanoma and exposure to ultraviolet light. Between the years 1978 and 1982, a study in Denmark shows an annual age-adjusted incidence of 8.4 cases per 100,000 in women and 6.1 cases per 100,000 in men. Women develop melanoma more frequently than men until the age of 80 years. Studies support the finding that patients who tan poorly and burn easily tend to be more at risk than those who tan easily and do not develop burning on exposure to ultraviolet light. Epidemiological evidence strongly suggests that malignant melanoma is associated with white-skinned individuals who have a significant amount of intermittent exposure to natural sunlight. Studies in Germany report that melanoma patients have significantly more benign melanocytic moles or nevi with a diameter of 2 millimeters or more. Recent work also indicated an association between so called dysplastic nevi or clinically atypical nevi and increased risk of melanoma. A study in Scotland showed a significant association between episodes of severe sunburn 5 years or less prior to development of the malignant melanoma. Exposure to ultraviolet light is linked to the etiology of malignant melanoma. It is possible that the temporary reduction in the immune system's capacity following exposure of animals to ultraviolet radiation may be associated with the development of the malignancy. The use of modern sunbeds emitting only ultraviolet A is a risk factor for malignant melanoma. The prospects for primary prevention of the disease are relatively poor. However, information on the strength of ultraviolet B radiation from the sun around noon and encouragement to avoid sun exposure on Mediterranean beaches or their equivalent between the hours of 11 a.m. and 3 p.m. will help. The provision of shade by tree-planting campaigns and programs near beaches, swimming pools, and public parks is also encouraged. The use of appropriate clothing to shield skin from strong sunlight is very important. The use of sun screens is recommended. Individuals should be encouraged to use products with high sunprotection factor (SPF) numbers on themselves and on their children at the beginning of a vacation and only slowly reduce the SPF number of the preparation as the skin acclimatizes to the sun. 17 references.
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Screening for Malignant Melanoma: State of the Art on Screening for Melanoma Source: in Cancer Screening. Miller, A.B. Chamberlain, J. Day, N.E. Hakama, M. Prorok, P.C. eds. Cambridge, England, Cambridge University Press, pp. 241-285, 1991. Contact: Press Syndicate of the University of Cambridge, 40 West 20th Street, New York, NY 10011-4211. Summary: Screening for Malignant Melanoma: State of the Art on Screening for Melanoma, a section in Cancer Screening, reviews methods, trials, and studies associated with the detection of malignant melanoma. Chapters include (1) Screening and Early Diagnosis for Melanoma in Australia and New Zealand, (2) Screening for
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Melanoma in the United Kingdom, (3) Screening for Melanoma/Skin Cancer in the United States, (4) The Dysplastic Nevus Syndrome Implications for Screening, and (5) Summary of the Discussion On Screening for Melanoma of the Skin. Screening for malignant melanoma is still in the early stages of development. No studies have determined the impact of screening on mortality; therefore, there is no recommended public health policy for screening. However, it is hoped that health promotion programs advocating enhanced individual awareness may be beneficial. Malignant melanoma is a candidate site for screening since the disease incidence is increasing and survival is greatly determined by lesion thickness. Visual examination is the only available screening test; it is relatively nonspecific and, on a wide scale, could require a substantial time commitment by health professionals. In many areas there are campaigns to promote limited sun exposure, use of sunscreens, self-examination, and prompt response to abnormalities. No program has been associated with reduction in mortality in the population and none of the programs have been organized on a population basis. The sensitivity and specificity of the skin examination are unknown although programs should involve monitoring of specificity, costs, and compliance through followup. Presently there is insufficient information for primary care practitioners about who should be referred for further evaluation. Studies also indicate the controversial role of dysplastic nevus syndrome in the natural history of and screening for melanoma. The syndrome is seen in 2 to 8 percent of the melanoma-free population and in about 33 percent of melanoma patients and clinical and histological features are not agreed upon.
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CHAPTER 8. MULTIMEDIA ON SKIN CANCER Overview In this chapter, we show you how to keep current on multimedia sources of information on skin 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 skin cancer is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “skin 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 “skin cancer” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on skin cancer: •
Skin Cancer at Time of Diagnosis Source: New York, NY: Patient Education Media, Inc./ Time Life Medical. 1996. ( VHS videocassette)... PD.-1/2 in VHS videocassette (30 min), col. Contact: Patient Education Media, Inc./ Time Life Medical. Time and Life Building, 1271 6th Street, New York, NY 10020. (212) 522-8089. (212) 522-8092 (fax). (800) 588-9959. PRICE: $19.95. Stock Number TLMV228. Summary: This 30-minute videocassette on skin cancer is divided into the following four parts: Part 1 uses computer animation to explain what is going on inside the body and how a skin cancer diagnosis is made; Part 2 discusses what happens after the diagnosis and introduces practical issues, such as types of health professionals who may become involved and what lifestyle changes may need to occur, including self-examination; Part 3 explores options for treatment and management of each condition; and Part 4 addresses issues and answers questions that frequently arise through the use of instudio question and answer sessions. The videotape is accompanied by a patient
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workbook that provides program highlights, a glossary of terms, a resource guide and a personal journal. •
Skin Cancer: Can You Spot It? Source: New York, NY, Skin Cancer Foundation, 3-minute VHS videotape, 1995. Contact: Skin Cancer Foundation, P.O. Box 561, New York, NY 10156. Summary: Skin Cancer: Can You Spot It? explains that one in five Americans will get skin cancer at some time. Untreated, it can lead to disfigurement and death. Almost all skin cancers are curable if detected early enough and treated promptly. Skin selfexamination of the whole body should be done regularly. One can use a hand mirror to check hard-to-see areas, and a blow dryer to look at the scalp. Look for any changes in the skin, such as changes to a mole or growth of a new mole or spot. Notice if the color is brown, black, or tan, pearly, or multicolored. Also note any changes in moles or birthmarks in size, thickness, or texture; look for irregular outline; and watch for size bigger than a pencil eraser. Note if the area bleeds or does not heal. If one sees anything that is suspicious, one needs to see a physician right away for evaluation. Skin selfexamination saves lives. The toll-free telephone number of the Skin Cancer Foundation, (800) SKIN-490, is given.
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Skin Cancer: Preventable and Curable Source: New York, NY, Skin Cancer Foundation, 15-minute VHS videotape, 1990. Contact: Skin Cancer Foundation, P.O. Box 561, New York, NY 10156. Summary: Skin Cancer: Preventable and Curable, narrated by talk show host Dick Cavett, teaches the viewer about risk factors for developing skin cancer, warning signs, how to identify skin cancer, and how to prevent it. The video discusses the importance of the ozone layer and ultraviolet rays (UVA and UVB), and presents a graph showing how deeply each type of ray penetrates skin. Excess sun exposure causes sunburn, premature aging, wrinkles, and 90 percent of all skin cancers. Anyone can get skin cancer, but some people are more vulnerable than others. The risk is greatest for those classified as having skin type one: Fair skin; red, light brown, or blonde hair; green, blue or gray eyes. Skin types are classified up to type six: Having dark skin and eyes and never burning. Risk factors also include having a history of blistering burns in childhood, or family history of skin cancer. Types of skin cancer include basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. Pictures of actual cases are shown for each type of cancer. Each is treatable and curable if detected early, even malignant melanoma. Untreated, there is a chance of metastasis and eventual death. Skin self-examination is very important. One can use a hand mirror to check hard-to-see areas, and a blow dryer to look at the scalp. Look for any changes in the skin, such as changes to a mole or growth of a new mole or spot. Notice if the mole or spot is asymmetrical, has irregular borders, has changes in color, and is bigger than a pencil eraser. If one sees anything that is suspicious, one should see a physician right away for evaluation. Tips on preventing skin cancer include avoiding peak sun hours, wearing protective clothing and a sunscreen of Sun Protection Factor 15 or higher, protecting children from sun exposure, not working on a tan either outdoors or at a tanning salon, and performing regular skin examination. The address of the Skin Cancer Foundation, P.O. Box 561, New York, NY 10156, is given.
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Detecting Early Melanoma Source: Atlanta, GA, American Cancer Society, 1 VHS videotape, 13:25-min., 1990. Contact: American Cancer Society, 1599 Clifton Road, NE., Atlanta, GA 30329. ACS Code: 3782.05. Summary: Detecting Early Melanoma is a videotape, with narrative provided. A dermatologist discuses skin cancer risks, symptoms, and prevention. People today have a 1 in 120 risk of developing malignant melanoma, the most serious form of skin cancer. Malignant melanoma tends to metastasize, but is curable if found in its early stages. The physician needs good eyes, good light, and perhaps a magnifying glass, and should use these tools to perform a thorough skin examination on patients. Many melanomas are found on the upper back in men and on the legs in women, but skin cancer can occur on any body part. The ABCD Rule of signs is given: Look for moles or growths that are Asymmetrical, have Border irregularity, have Color variegation, and are greater than 6 millimeters in Diameter. Color slides in this video demonstrate the different appearances of moles that are normal versus those that are skin cancers. Other signs of cancer are crusting, bleeding, not healing, or moles with a blue/black color; these should all be biopsied. Dysplastic nevi may be cancer precursors and should be followed carefully. Biopsies can usually be done with local anesthesia in the office. Risks for developing melanoma include fair skin, previous personal or family history, immunosuppressive patients, and/or those who had blistering sunburns, especially early in life. Blacks can develop skin cancer, under their nails and on palms and soles. A nurse demonstrates teaching a male patient how to do a thorough skin self examination. Patients can also keep body charts to note location of moles. Prevention is stressed, including avoidance of tanning, use of sunscreen, wearing protective clothing in the sun, and avoiding midday sun.
Bibliography: Multimedia on Skin 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 skin 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 skin cancer: •
Benign skin growths; Skin cancer: pre-malignant and malignant growths (nonmelanoma); The atypical (dysplastic) nevus; Malignant melanoma [videorecording] Source: produced for the Canadian Association of Professors of Dermatology by Roberta Ongley; Biomedi; Year: 1993; Format: Videorecording; [Vancouver, B.C.]: The University, c1993
•
Control and prevention of malignant melanoma [videorecording]: a program for melanoma-prone families Source: the Pigmented Lesion Study Group, the University of Pennsylvania [and] the Environmental Epidemiology Branch of the National Cancer Institute; Year: 1981; Format: Videorecording; Washington, DC: National Audiovisual Center, [1981]
•
Dysplastic nevi and melanoma [videorecording]: a program for pathologists Source: Pigmented Lesion Study Group, the University of Pennsylvania, the Environmental
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Epidemiology Branch of the National Cancer Institute; Year: 1981; Format: Videorecording; Washington, D.C.: National Audiovisual Center, [1981] •
Head to toe [videorecording]: the role of primary care physicians in detecting skin cancer Source: a collaboration between Univesity of California, San Francisco and Kaiser Permanente; Year: 1996; Format: Videorecording; [Berkeley, Calif.]: Regents of the University of California, c1996
•
Melanoma [videorecording]: winning the battle against skin cancer Source: a presentation of Films for the Humanities & Sciences; ITV, Information Television Network; Year: 1997; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c1997
•
Microscopically controlled excision of skin cancer [videorecording]: Mohs' technique Source: produced by Health Communications Network, Division of Continuing Education, Medical University of South Carolina; Year: 1982; Format: Videorecording; Charleston, S.C.: The Division, c1982
•
Safe and effective use of low energy X rays for the treatment of skin cancer [videorecording] Source: U.S. Department of Health and Human Services, Public Health Service, Food and Drug Administration, Bureau of Radiological Health; Year: 1982; Format: Videorecording; Rockville, Md.: The Bureau, 1982
•
Skin cancer Source: Arthur J. Sober, Frank G. Haluska; Year: 2000; Format: Edited by; Hamilton, Ont. Lewiston, NY: B C Decker, 2001
•
Skin cancer [slide] Source: Gerald D. Weinstein; Year: 1973; Format: Slide; New York: Medcom, c1973
•
Skin cancer [slide] Source: [produced and published by Gower Medical Publishing]; Year: 1991; Format: Slide; New York, NY: Gower Medical Pub., c1991
•
Skin cancer [videorecording] Source: Instructional Systems Development Service; [made by] Penn State Television; Year: 1979; Format: Videorecording; University Park, Pa.: Pennsylvania State Univ.: [for loan or sale by its Audio-Visual Services], 1979
•
Skin cancer [videorecording] Source: University of Texas, System Cancer Center, M. D. Anderson Hospital and Tumor Institute; produced by MDA-TV; Year: 1973; Format: Videorecording; Houston: The Center, 1973
•
Skin cancer [videorecording] Source: [presented by] Medical University of South Carolina, College of Medicine and Health Communications Network; Year: 1992; Format: Videorecording; Charleston, S.C.: The University, c1992
•
Skin cancer [videorecording] Source: Time Life Medical; produced in association with Sonalysts Studios; Year: 1996; Format: Videorecording; New York, NY: Patient Education Media, c1996
•
Skin cancer [videorecording]: the undeclared epidemic Source: American Academy of Dermatology; Year: 1988; Format: Videorecording; Schaumberg, IL: The Academy, 1988
•
Skin cancer and dermatitis factitia [videorecording] Source: Dept. of Medicine, Emory University, School of Medicine; Year: 1979; Format: Videorecording; Atlanta: Emory Medical Television Network: [for loan and sale by A. W. Calhoun Medical Library, 1979]
•
Skin cancer, melanoma, and aging skin [videorecording] Source: [presented by] Journal of women's health; Year: 1993; Format: Videorecording; Bethesda, Md.: BioConferences International, c1993
•
Skin diseases: scabies, malignant melanoma [videorecording]: a report Source: Donald P. Lookingbill; [made by] Penn State Television; Year: 1977; Format: Videorecording; University Park, Pa.: Pennsylvania State University: [for loan or sale by its Audio-Visual Services], c1977
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•
Stopping skin cancer [videorecording]: before and after it starts Source: Perry Robins; Year: 1984; Format: Videorecording; New York: NCME, 1984
•
Sunlight and skin cancer [videorecording]. Year: 1993; Format: Videorecording; Princeton, N.J.: Films for the Humanities, c1993
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CHAPTER 9. PERIODICALS AND NEWS ON SKIN CANCER Overview In this chapter, we suggest a number of news sources and present various periodicals that cover skin cancer.
News Services and Press Releases One of the simplest ways of tracking press releases on skin 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 “skin 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 skin 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 “skin cancer” (or synonyms). The following was recently listed in this archive for skin cancer: •
US advisers reject PhotoCure's skin cancer therapy Source: Reuters Industry Breifing Date: September 10, 2003 http://www.reutershealth.com/archive/2003/09/10/business/links/20030910rglt003. html
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•
US FDA advisers to weigh new skin cancer therapy Source: Reuters Industry Breifing Date: September 09, 2003
•
3M seeks skin cancer indication for Aldara Source: Reuters Industry Breifing Date: June 11, 2003
•
Melanoma incidence has doubled in Germany over past decade Source: Reuters Medical News Date: May 09, 2003
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Melanoma mortality greater in UK than in Australia Source: Reuters Industry Breifing Date: March 27, 2003
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Some radiologic technologists at increased risk for melanoma Source: Reuters Medical News Date: March 03, 2003
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A little sun may boost kids' skin cancer risk Source: Reuters Health eLine Date: February 12, 2003
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Melanoma survivors shouldn't be organ donors: study Source: Reuters Health eLine Date: February 05, 2003
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Skiers at risk for skin cancer: experts Source: Reuters Health eLine Date: January 28, 2003
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Vitamins/carotenoids not likely to protect against squamous cell skin cancer Source: Reuters Medical News Date: January 10, 2003
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Allergan licenses plant-based skin cancer drug Source: Reuters Industry Breifing Date: November 25, 2002
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Dermatoscope plus computer imaging can yield rapid melanoma diagnosis Source: Reuters Industry Breifing Date: November 21, 2002
Periodicals and News 417
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Melanoma screening should target men over 50 years of age Source: Reuters Medical News Date: October 15, 2002
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QLT, Novartis move eye disease drug into phase III trials for skin cancer Source: Reuters Industry Breifing Date: October 11, 2002
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Australia tan implants may help prevent skin cancer Source: Reuters Industry Breifing Date: September 05, 2002
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Location and subtype of nonmelanoma skin cancer predicts risk of spread Source: Reuters Medical News Date: August 27, 2002
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Rapid squamous cell skin cancer growth seen in HIV-infected patients Source: Reuters Medical News Date: June 25, 2002
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Celecoxib may help prevent skin cancer Source: Reuters Industry Breifing Date: June 24, 2002
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Parotidectomy often needed in aggressive head and neck skin cancers Source: Reuters Medical News Date: May 28, 2002
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Australia unveils melanoma detection device Source: Reuters Industry Breifing Date: May 07, 2002
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Skin cancer rates soaring in British men Source: Reuters Health eLine Date: March 28, 2002
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Melanin density inversely tied to skin cancer risk in Caucasians Source: Reuters Medical News Date: March 27, 2002
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EntreMed's Endostatin gets orphan drug designation for melanoma Source: Reuters Industry Breifing Date: February 28, 2002
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Novel combination chemotherapy regimen effective for squamous skin cancer Source: Reuters Medical News Date: February 11, 2002
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New sun warnings as UK skin cancer deaths rise Source: Reuters Health eLine Date: February 07, 2002
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Tanning beds, lamps raise skin cancer risk: study Source: Reuters Health eLine Date: February 06, 2002
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Use of tanning devices linked to basal and squamous cell skin cancers Source: Reuters Medical News Date: February 05, 2002
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DNA repair ability affects risk of melanoma: study Source: Reuters Health eLine Date: January 16, 2002
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Cyclosporin increases skin cancer risk in PUVA-treated psoriasis patients Source: Reuters Medical News Date: September 27, 2001
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Curis to initiate phase I trial on potential basal cell carcinoma treatment Source: Reuters Industry Breifing Date: September 05, 2001
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Severe psoriasis linked with lymphoma, nonmelanoma skin cancer Source: Reuters Medical News Date: June 18, 2001
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Psoriasis therapy ups long-term melanoma risk Source: Reuters Health eLine Date: May 25, 2001
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Interferon best therapy for advanced skin cancer Source: Reuters Health eLine Date: April 30, 2001
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Sun seekers not deterred by skin cancer threat Source: Reuters Health eLine Date: April 25, 2001
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Foods, vitamins may shield against skin cancer Source: Reuters Health eLine Date: April 25, 2001
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Drug prevents depression in skin cancer patients Source: Reuters Health eLine Date: March 29, 2001
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PhotoCure seeks Australian approval for light-activated skin cancer therapy Source: Reuters Industry Breifing Date: March 15, 2001
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Computerized dermoscopic technique may improve diagnosis of melanoma Source: Reuters Medical News Date: February 27, 2001
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In rare cases, melanoma can occur in children Source: Reuters Health eLine Date: February 26, 2001
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Study connects melanoma and non-Hodgkin's lymphoma Source: Reuters Health eLine Date: February 23, 2001
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Skin cancers in hidden locations thicker than "public" melanomas Source: Reuters Medical News Date: February 21, 2001
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Herpes virus may help treat skin cancer Source: Reuters Health eLine Date: February 16, 2001
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Clinton treated succesfully for skin cancer Source: Reuters Health eLine Date: January 17, 2001
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Bacteria harnessed to battle skin cancer Source: Reuters Health eLine Date: January 12, 2001
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Switched-off gene may make skin cancer aggressive Source: Reuters Health eLine Date: January 10, 2001
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•
Smoking nearly triples the risk of squamous skin cancer Source: Reuters Medical News Date: December 28, 2000
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Skin cancer screening may be underemployed in primary care Source: Reuters Medical News Date: December 27, 2000
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Skin cancers cured by poisonous weed Source: Reuters Medical News Date: December 08, 2000
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HPV may have role in skin cancer Source: Reuters Medical News Date: December 01, 2000
•
QLT's verteporfin may hold promise as skin cancer treatment Source: Reuters Industry Breifing Date: October 31, 2000 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 “skin 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 “skin cancer” (or synonyms). If you know the name of a company that is relevant to skin 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 “skin cancer” (or synonyms).
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 “skin 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 skin cancer: •
Skin Cancer: Is Sunscreen and Enabler? Source: Harvard Health Letter. 25(9): 1-3. July 2000. Contact: Available from Harvard Health Letter, P.O. Box 380, Department BI, Boston, MA 02117. (800) 829-9045 or (617) 432-1485. E-mail:
[email protected]. Summary: This newsletter article provides the general public with information on sun exposure and sunscreening agents. Although sunscreening agents stop sunburn by absorbing ultraviolet B (UVB) rays, they do not block other parts of the light spectrum that may have a role in causing skin cancer, particularly melanoma. The use of sunscreens may be giving people a false sense of security and enabling the intense, intermittent exposure to sunlight that happens over vacations. Studies on the sunscreen use and melanoma connection have been controversial. However, people should continue to use sunscreens because they do protect against sunburn. Although UVA light was once thought to be a harmless, tan producing part of the light spectrum, it is now known that UVA damages and ages the skin in various ways by initiating a molecular cascade that produces reactive forms of oxygen that damage DNA and cell membranes. UVA may also suppress the immune system. Most sunscreening products now available are broad spectrum and claim to protect against UVB and UVA. Sunscreens are made UVA protective by adding a chemical that absorbs UVA light or adding very finely ground zinc oxide to titanium oxide. However, these broad spectrum sunscreens do not block or absorb all the UVA light. An alternative to sunscreening agents is sun protective clothing. This type of clothing should have a tight weave and be
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dark. In addition, avoiding sun exposure between 10 a.m. and 4 p.m. may also help protect against skin cancer. •
Spotting and Curing Skin Cancer Source: Health After 50. 4-6; May 1997. Contact: Johns Hopkins Medical Letter, Health After 50, 550 North Broadway, Suite 1100, Baltimore, MD 21205-2011. Summary: This newsletter article for the general public provides guidelines for detecting skin cancers. It presents data on the incidence of skin cancer and describes the characteristics of basal and squamous cell cancer and melanoma. Steps for reducing the risk of skin cancer are outlined, including avoiding the sun during peak intensity; wearing sunglasses, a hat, and tightly woven clothes; and using sunscreen. In addition, the article discusses various methods of treating skin cancer, including curettage and electrodesiccation, conventional surgery, and Mohs' surgery.
Academic Periodicals covering Skin Cancer Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to skin cancer. In addition to these sources, you can search for articles covering skin cancer that have been published by 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 skin 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 DI Advice for the Patient 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 skin 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 skin cancer: Aldesleukin •
Systemic - U.S. Brands: Proleukin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202669.html
Bleomycin •
Systemic - U.S. Brands: Blenoxane http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202093.html
Carboplatin •
Systemic - U.S. Brands: Paraplatin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202115.html
Carmustine •
Systemic - U.S. Brands: BiCNU http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202117.html
Dacarbazine •
Systemic - U.S. Brands: DTIC-Dome http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202178.html
Daunorubicin, Liposomal •
Systemic - U.S. Brands: DaunoXome http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203539.html
Interferons, Alpha •
Systemic - U.S. Brands: Alferon N; Intron A; Roferon-A http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202299.html
Melphalan •
Systemic - U.S. Brands: Alkeran http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202345.html
Sunscreen Agents •
Topical - U.S. Brands: A-Fil; Aquaderm Sunscreen Moisturizer; Aquaray Sunscreen; Bain de Soleil All Day For Kids; Bain de Soleil All Day Sunfilter; Bain de Soleil Mega Tan; Bain de Soleil Orange Gelee; Bain de Soleil Sand Buster; Bain de Soleil SPF + Color; Bain de Soleil Tro http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202782.html
Tamoxifen •
Systemic - U.S. Brands: Nolvadex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202545.html
Vinblastine •
Systemic - U.S. Brands: Velban http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202593.html
Researching Medications 425
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 Consult Mosby’s Drug Consult 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 skin 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 (http://www.rarediseases.org/search/noddsearch.html), type “skin 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
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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 skin cancer: •
Interferon beta (recombinant) (trade name: R-IFN-beta) http://www.rarediseases.org/nord/search/nodd_full?code=101
•
Histamine (trade name: Maxamine) http://www.rarediseases.org/nord/search/nodd_full?code=1022
•
Deoxyribose, Phosphorothioate http://www.rarediseases.org/nord/search/nodd_full?code=1055
•
Cisplatin/epinephrine (trade name: IntraDose) http://www.rarediseases.org/nord/search/nodd_full?code=1066
•
Imexon (trade name: n/a) http://www.rarediseases.org/nord/search/nodd_full?code=1172
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Monoclonal Ab(murine) anti-idiotype melanoma-asso (trade name: Melimmune) http://www.rarediseases.org/nord/search/nodd_full?code=123
•
recombinant human endostatin protein (trade name: NONE Assigned) http://www.rarediseases.org/nord/search/nodd_full?code=1251
•
autologous tumor-derived gp96 heat shock protein-p (trade name: Oncophage) http://www.rarediseases.org/nord/search/nodd_full?code=1259
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recombinant human endostatin protein http://www.rarediseases.org/nord/search/nodd_full?code=1284
•
Interleukin-2 (trade name: Teleleukin) http://www.rarediseases.org/nord/search/nodd_full?code=130
•
DHA-pacitaxel (trade name: Taxoprexin) http://www.rarediseases.org/nord/search/nodd_full?code=1302
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Interleukin-2 (trade name: Teceleukin) http://www.rarediseases.org/nord/search/nodd_full?code=133
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Technetium Tc 99m anti-melanoma murine monoclonal (trade name: Oncotrac Melanoma Imaging Kit) http://www.rarediseases.org/nord/search/nodd_full?code=307
•
Poly I: poly C12U (trade name: Ampligen) http://www.rarediseases.org/nord/search/nodd_full?code=406
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Melanoma cell vaccine http://www.rarediseases.org/nord/search/nodd_full?code=52
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•
Interferon alfa-2a (recombinant) (trade name: Roferon-A) http://www.rarediseases.org/nord/search/nodd_full?code=542
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Amifostine (trade name: Ethyol) http://www.rarediseases.org/nord/search/nodd_full?code=533
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Melanoma vaccine (trade name: Melacine) http://www.rarediseases.org/nord/search/nodd_full?code=67
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Beta alethine (trade name: Betathine) http://www.rarediseases.org/nord/search/nodd_full?code=832
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MART-1 adenoviral gene therapy for malignant melan http://www.rarediseases.org/nord/search/nodd_full?code=833
•
Temozolomide (trade name: Temodal) http://www.rarediseases.org/nord/search/nodd_full?code=948
•
gp100 adenoviral gene therapy http://www.rarediseases.org/nord/search/nodd_full?code=837
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Aldesleukin (trade name: Proleukin) http://www.rarediseases.org/nord/search/nodd_full?code=873
•
Interferon alfa-2a (recombinant) (trade name: Roferon-A) http://www.rarediseases.org/nord/search/nodd_full?code=91
•
Melphalan (trade name: Alkeran for Injection) http://www.rarediseases.org/nord/search/nodd_full?code=92
•
Autologous DNP-conjugated tumor vaccine (trade name: M-Vax) http://www.rarediseases.org/nord/search/nodd_full?code=964
•
Pegylated arginine deiminase (trade name: Melanocid) http://www.rarediseases.org/nord/search/nodd_full?code=977
•
HLA-B7/Beta2M DNA Lipid (DMRIE/DOPE) Complex (trade name: Allovectin-7) http://www.rarediseases.org/nord/search/nodd_full?code=992
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 “skin 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 “skin cancer” (or synonyms) into the “For these words:” box. The following is a sample result: •
Skin Cancer Prevention: Strategic Plan for New South Wales 2001-2005 Source: Sidney, Australia, Cancer Council New South Wales, 89 p., 2001. Contact: Cancer Council New South Wales, 153 Dowling Street, Woolloomooloo, New South Wales 2011, Australia. 02-9334-1900. FAX: 02-9326-9328. INTERNET/EMAIL: http://www.health.nsw.gov.au/public_health/health-promotion/pdf/sunpro/ canstrat01-05.pdf. State Health Publication no. HP01008. Summary: Skin Cancer Prevention: Strategic Plan for New South Wales 2001-2005 offers a framework for developing local action plans to ensure that skin cancer prevention is maintained as a high priority throughout the state. The goal of this effort is to reduce the incidence of skin cancer and related morbidity and mortality among the population of New South Wales by using strategies to reduce exposure to ultraviolet radiation. The report identifies (1) three priority populations (children age 0 to 11 years, adolescents age 12 to 19 years, and adults with high intermittent or cumulative exposure); and (2) five priority settings (early childhood services, schools, sports and recreation, local government, and workplaces). It provides an overview of the scientific and epidemiological rationale for skin cancer prevention programs, then outlines strategic directions (e.g., policy context for the strategic plan, guiding principles, the basis for choosing priority population groups, settings, and kinds of strategies proposed). The next section offers an overview of the strategic plan, summarizing the long-term and immediate outcomes needed to reduce the incidence of and mortality from skin cancer in New South Wales. Finally, the report discusses proposed population and settings monitoring for children, adolescents, and adults. The plan provides (1) recommendations for regional or area-based activities, (2) an outline of the proposed state-level support for these approaches, and (3) suggested partner organizations.
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Preventing Skin Cancer: The Nation's Most Common Cancer: At a Glance: 1999: Choose Your Cover Source: Atlanta, GA, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 3-fold brochure, 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.,
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Atlanta, GA 30341-3717. (770) 488-4751. FAX: (770) 488-4760. INTERNET/EMAIL: http://www.cdc.gov/cancer;
[email protected]. Summary: Preventing Skin Cancer: The Nation's Most Common Cancer: At a Glance: 1999: Choose Your Cover examines the Centers for Disease Control and Prevention's (CDC's) Choose Your Cover public service campaign to promote sun protection. The CDC convened the National Council on Skin Cancer Prevention to facilitate national skin cancer awareness and prevention efforts through education and promotion of sunsafe behavior. The Council's objectives are to (1) increase skin cancer awareness and prevention behavior in all populations, (2) develop and support partnerships to reinforce core messages for behavior change, (3) coordinate a public health response to nationwide efforts to reduce skin cancer, and (4) develop a national plan to address the continuum of existing activities. This publication promotes (1) wearing hats, (2) seeking shade, (3) wearing protective clothing, (4) using sunscreens, and (5) wearing sunglasses. Risk factors for skin cancer listed in this pamphlet are (1) fair complexion, (2) family history, (3) personal history of skin cancer, (4) chronic sun exposure, (5) history of sunburns early in life, (6) atypical moles, (7) a large number of moles, and (8) freckles. This pamphlet briefly describes (1) the CDC's national leadership in skin cancer prevention, (2) the CDC's epidemiological research and monitoring systems, (3) individual state programs that have extended the reach of the Choose Your Cover campaign, and (4) support for skin cancer prevention education initiatives. Projects currently funded by the CDC include (1) Sunwise Stampede; (2) Covering the Waterfront; (3) the National Coalition for Skin Cancer Prevention in Health, Physical Education, Recreation, and Youth Sports; and (4) Coalition for Skin Cancer Prevention. Five recently completed projects in Arizona, California, Georgia, Hawaii, and Massachusetts, which were supported by the CDC, addressed innovative strategies for skin cancer prevention education targeting children and their families. •
National Skin Cancer Prevention Education Program: At-a-Glance, 1998 Source: Atlanta, GA, US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, 4 p., 1998. 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. INTERNET/EMAIL:
[email protected]; http://www.cdc.gov/nccdphp/dcpc. Summary: National Skin Cancer Prevention Education Program: At-A-Glance, 1998 is a fact sheet that describes the activities of the Centers for Diasease Control and Prevention's (CDC) National Skin Cancer Education Program and presents information on the epidemiology of skin cancer, risk factors for skin cancer, and guidelines for preventing skin cancer. Skin cancer is the most rapidly increasing form of cancer in the United States, with more than 1 million new cases of basal cell and squamous cell carcinoma combined and 41,600 new cases of malignant melanoma expected to be diagnosed in 1998. Nearly 9,200 deaths from skin cancer are expected in 1998. Risk factors for skin cancer include light skin color, family history of skin cancer, personal history of skin cancer, chronic exposure to the sun, history of severe sunburns early in life, certain types and a large number of moles, and freckling as an indicator of sun sensitivity and sun damage. Recommendations for preventing skin cancer include reducing direct exposure to the sun. When direct sun exposure cannot be avoided, wear a broad-brimmed hat, long-sleeved shirt, long pants, and sunglasses; use sun screen lotion having a sun protection factor of at least 15 to protect against ultraviolet (UV) A and B radiation; refer to the daily UV index, provided in local weather forecasts, when
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planning outdoor activities; and avoid artificial sources of UV light such as tanning beds and sun lamps. Activities of CDC's National Skin Cancer Prevention Education Program for fiscal year 1998 include: developing a national coalition of federal agencies, professional and voluntary organizations, and the private sector to coordinate national efforts to prevent skin cancer and educate the public about skin cancer prevention; launching a CDC national skin cancer prevention program in early summer 1998; supporting development of the Health, Physical Education, and Recreation Coalition for Skin Cancer Prevention Education; supporting a state-based coalition for skin cancer prevention education; supporting development and implementation of an intervention at a zoological park to promote UV protective behaviors in children; supporting the University of Hawaii and Boston University School of Medicine in providing sun protection education at swimming sites; and developing epidemiological research and surveillance systems for monitoring program effectiveness and national trends and attitudes. The CDC, in partnership with the Prevention Research Center Program at the University of Alabama, Birmingham, is developing national skin cancer prevention guidelines for schools and communities to address sun protection issues for children in prekindergarten through the 12th grade. •
Action Plan on Skin Cancer for the State of Texas Source: Austin, TX, Texas Cancer Council, 52 p., August 2000. Contact: Texas Cancer Council, P.O. Box 12097, Austin, TX 78711. (512) 463-3190. Summary: Action Plan on Skin Cancer for the State of Texas identifies current skin cancer education, prevention, detection, and treatment resources, recommending approaches and resources that must be developed to thoroughly evaluate and reduce the incidence of skin cancer in the state. It takes into account the demographic diversity of its people and the urgency of making skin cancer awareness and prevention a part of daily life. The report discusses (1) incidence, mortality, and impact on society; (2) basal cell carcinoma, squamous cell carcinoma, and malignant melanoma; (3) contributing and causative factors, including ultraviolet radiation; (4) prevention; (5) cancer prevention and information services that impact the skin cancer problem; (6) barriers to early detection and treatment of skin cancer in Texas; (7) policy initiatives that would affect skin cancer awareness and prevention; (8) professional practice regarding skin cancer prevention, detection, and treatment; and (9) prevention and information models. The Action Plan includes four goals: (1) Initiate data collection and analysis; (2) develop prevention information and services to increase public awareness; (3) enhance professional education and practice; and (4) improve access to prevention, detection, and treatment. Appendices provide data on skin cancer morbidity and mortality, counties reporting health care availability as an issue, federally designated medically underserved areas, and additional Texas Cancer Council initiatives.
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Summary of the National Forum for Skin Cancer Prevention in Health, Physical Education, Recreation, and Youth Sports Source: Reston, VA, AAHE/AAHPERD Publications, 30-page booklet, 1998. Contact: American Association for Health Education, American Alliance for Health, Professional Education, Recreation and Dance, 1900 Association Drive, Reston, VA 20191. (800) 321-0789. Summary: The National Forum for Skin Cancer Prevention in Health, Physical Education, Recreation, and Youth Sports was hosted in May of 1998 by the American Association for Health Education and the American Alliance for Health, Physical
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Education, Recreation and Dance. Representatives from more than 25 national organizations and governmental offices assessed the state of skin cancer prevention strategies in the health, physical education, recreation, and youth sports settings. Six objectives guided the planning of the forum: (1) Identification of organizational issues, experiences, and barriers in relation to skin cancer prevention; (2) identification and description of health messages important to populations served; (3) examination of existing skin cancer prevention policies and rules within organizations; (4) exploration of potentials in cancer prevention interventions for leadership, health, physical education, recreation, and youth sports; (5) development of an awareness of resources and incentives needed to plan and implement skin cancer prevention interventions; and (6) promotion of action in support of skin cancer prevention within the National Coalition for Skin Cancer Prevention in Health, Physical Education, Recreation, and Youth Sports. These objectives provided direction for small breakout group discussions and one large group discussion. Breakout group topics were entitled (1) Barriers, (2) Messages/policy, (3) Intervention, and (4) Action Plan Proposal. In addition to the discussions, speakers offered presentations concerning skin cancer prevention initiatives as put forward by the Centers for Disease Control and Prevention. This report provides the presentation highlights, summarizes the small group discussions, and draws conclusions from the forums. It also includes a listing of references, forum participants, and coalition members. •
Attitudes to Sunbathing and the Risks of Skin Cancer Source: London, England, Health Education Authority, 11 p., 1997. Contact: Health Education Authority, Hamilton House, Mabledon Place, London, WC1H 9TX, England. Summary: Attitudes to Sunbathing and the Risks of Skin Cancer describes the results of a large-scale qualitative research project to gain a better understanding of the motivations involved in why sunbathing still seems to appeal to many people in the United Kingdom, despite the publicity about the risks of skin cancer. Researchers conducted group discussions and interviews with people from four target groups: (1) Parents and caretakers of young children, (2) children age 8 to 11, (3) young people age 12 to 18, and (4) adults age 19 to 35. Results showed that (1) sunshine has a positive effect on morale; (2) tanning starts to appeal from the adolescent years onward; (3) people, including young children, continue to sunbathe despite knowing that there are risks involved; (4) reasons for the marginal impact of the health education message about sunbathing are people's attitudes, perceived low risk, limited sun exposure, safe sunbathing, relatively harmless pleasure, and a tan is worth the risk; and (5) promoting concern for health at the expense of a tan is hard. The author concludes that (1) a health education campaign to persuade people that sunbathing may lead to skin cancer would be ignored because the appeal of a tan is so great, and people's experiences of the risks are limited; and (2) people would welcome more information about sunbathing and the risks of skin cancer, and about the relationship between different skin types and the risks of developing skin cancer.
•
Skin Cancers: Basal Cell and Squamous Cell Carcinomas Source: Bethesda, MD, US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute, 17 p., September 1990.
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Contact: National Cancer Institute, Office of Cancer Communications, Publications Order, Building 31, Room 10A-24, 9000 Rockville Pike, Bethesda, MD 20892. (800) 4CANCER. NIH Publication No. 91-2977. Summary: Skin Cancers: Basal Cell and Squamous Cell Carcinomas summarizes current knowledge on the incidence and mortality, risk factors, prevention, detection and diagnosis, and treatment of basal cell and squamous cell carcinomas, the two most common types of skin cancer. The information comes from (1) National Cancer Institute (NCI) researchers and other scientists, (2) an NCI database, (3) medical textbooks, (4) recent articles in the scientific literature, and (5) various scientific meetings. The report expands on the information provided in the NCI pamphlet What You Need to Know About Skin Cancer. Together, basal cell and squamous carcinomas are referred to as nonmelanoma skin cancers. There are approximately 600,000 new cases of nonmelanoma skin cancer in the United States each year, and it is the most common cancer among whites in the United States. The report describes a variety of risk factors, noting that the most important risk factor is ultraviolet radiation from the sun or tanning devices. The most effective prevention measure for nonmelanoma cancers is reduced exposure to the sun. Individuals at high risk should conduct regular examinations for changes in the skin and get regular physician examinations. When cancer is diagnosed, the physician needs to know the stage of the disease in order to plan the best treatment. Several types of treatment are effective, and more than 95 percent of patients with nonmelanoma skin cancer are completely cured. Treatments include surgery, curettage, cryosurgery, Mohs' technique, radiation therapy, topical chemotherapy, and carbon dioxide laser. The report concludes by explaining followup care and describing investigational therapies. •
Melanoma Cancer in Wyoming Source: Wyoming Cancer Surveillance Program, 4 p., 0000. Contact: INTERNET/EMAIL: http://wdhfs.state.wy.us/cancer/melanoma.htm. (accessed December 28, 2000). Summary: Melanoma Cancer in Wyoming is a report by the Wyoming Cancer Surveillance Program on the incidence of melanoma in Wyoming. The Wyoming Cancer Surveillance Program collects data from hospitals and clinics across the state. Melanoma is the seventh most common cancer in the United States with an estimated 44,200 new cases and 7,800 deaths in 1999. Wyoming ranked second highest in the United States for melanoma mortality from 1991 to 1995. Possible reasons for the increase in incidence include extended recreational exposure to the sun and thinning of the ozone layer. People who have had three or more severe sunburns as a child or adolescent are at greatest risk for developing melanoma. Skin cancer incidence rates are 10 times higher for whites than blacks, and skin cancer is more common among people with fair skin. The existence of atypical or dysplastic moles is an indicator of increased risk. In Wyoming, melanoma is the fifth most reported cancer for men and the seventh most reported cancer for women. During this period, 313 people were diagnosed with invasive melanomas, and the average annual incidence rate for 1992 to 1996 was 12.0 per 100,000. The national average incidence rate for 1991 to 1995 was 12.7 per 100,000. In Wyoming, 73 percent of reported melanoma cases were diagnosed in the early stages. Only 6 percent were reported in the late stages.
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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 “skin cancer” (or synonyms) into the search box and click “Search.” The results will 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 59429 504 314 118 5 60370
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 “skin 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 15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
16
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). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19
The HSTAT URL is http://hstat.nlm.nih.gov/.
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.
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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/.
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 Skin Cancer In the following section, we will discuss databases and references which relate to the Genome Project and skin 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 “skin 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 skin cancer:
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. 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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•
Melanoma Differentiation-associated Gene 5 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606951
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Melanoma, Cutaneous Malignant Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?155600
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Melanoma-astrocytoma Syndrome Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?155755 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
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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
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Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner
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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 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
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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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
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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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 “skin cancer” (or synonyms) into the search box and click “Go.”
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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 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 “skin 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 National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 25 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 skin 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 skin 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 skin 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 “skin cancer”:
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Guides on skin cancer Melanoma http://www.nlm.nih.gov/medlineplus/tutorials/melanomaloader.html
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Other Guides Cancer http://www.nlm.nih.gov/medlineplus/cancergeneral.html Eye Cancer http://www.nlm.nih.gov/medlineplus/eyecancer.html Melanoma http://www.nlm.nih.gov/medlineplus/melanoma.html Sun Exposure http://www.nlm.nih.gov/medlineplus/sunexposure.html Vulvar Cancer http://www.nlm.nih.gov/medlineplus/vulvarcancer.html
Within the health topic page dedicated to skin cancer, the following was listed: •
General/Overviews Skin Cancer http://www.nlm.nih.gov/medlineplus/tutorials/skincancerloader.html Skin Cancer: Saving Your Skin from Sun Damage Source: American Academy of Family Physicians http://familydoctor.org/healthfacts/159/index.html What Is Nonmelanoma Skin Cancer? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_is_skin_cancer_ 51.asp?sitearea=
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Diagnosis/Symptoms How Is Nonmelanoma Skin Cancer Diagnosed? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_3x_how_is_skin_cancer_diag nosed_51.asp?sitearea=cri How Is Nonmelanoma Skin Cancer Staged? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_3x_how_is_skin_cancer_stag ed_51.asp?sitearea=&level= How to Spot Skin Cancer Source: Skin Cancer Foundation http://www.skincancer.org/self_exam/spot_skin_cancer.html Melanoma: What to Look for Source: Skin Cancer Foundation http://www.skincancer.org/self_exam/look_for.html
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Treatment How Is Nonmelanoma Skin Cancer Treated? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_2_4X_How_Is_Nonmelano ma_Skin_Cancer_Treated_51.asp Merkel Cell Carcinoma (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/merkelcell/patient/ Skin Cancer (PDQ): Treatment Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/treatment/skin/patient/
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Specific Conditions/Aspects About Basal Cell Carcinoma Source: Skin Cancer Foundation http://www.skincancer.org/basal/index.php Basic Facts about Actinic Keratoses Source: American Academy of Dermatology http://www.skincarephysicians.com/actinickeratosesnet/basicFacts.htm Golfers and Skin Cancer Source: American Cancer Society http://www.cancer.org/docroot/nws/content/nws_2_1x_golfers_and_skin_cancer .asp Indoor Tanning: All the Dangers of the Outdoor Sun, Including Skin Cancer Source: American Academy of Dermatology http://www.aad.org/PressReleases/indoor.html Merkel Cell Cancer Source: National Cancer Institute http://cis.nci.nih.gov/fact/6_11.htm Skin Cancer Quiz: Test Your Knowledge about Skin Cancer Source: American Academy of Dermatology http://www.aad.org/SkinCancerNews/WhatIsSkinCancer/skinquiz.html Squamous Cell Carcinoma Source: American Academy of Dermatology http://www.aad.org/pamphlets/sqamous.html What Should You Ask Your Physician about Nonmelanoma Skin Cancer? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_5X_What_should_you_as k_your_physician_about_skin_cancer_51.asp?sitearea=
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Children ABCDs of Skin Cancer Source: American Academy of Dermatology http://www.aad.org/Kids/skincancer.html
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Sun Safety Source: Nemours Foundation http://kidshealth.org/parent/firstaid_safe/outdoor/sun_safety.html •
From the National Institutes of Health What You Need to Know about Skin Cancer Source: National Cancer Institute http://www.cancer.gov/cancerinfo/wyntk/skin
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Latest News Children at High Risk from Ozone Decline, UN Says Source: 09/16/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14013 .html FDA Advisers to Weigh New Skin Cancer Therapy Source: 09/09/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_13924 .html Health Experts Not Heeding Skin Cancer Warnings Source: 09/22/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14054 .html
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Men Skin Cancer: Men Who Care about Their Skin Protect It Source: American Academy of Family Physicians http://familydoctor.org/handouts/615.html
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Organizations American Academy of Dermatology http://www.aad.org/ American Cancer Society http://www.cancer.org/ American Society for Dermatologic Surgery http://www.asds-net.org/ National Cancer Institute http://www.cancer.gov/ Skin Cancer Foundation http://www.skincancer.org/
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Pictures/Diagrams What Do Actinic Keratoses Look Like? Source: American Academy of Dermatology http://www.skincarephysicians.com/actinickeratosesnet/lookLike.htm
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Prevention/Screening Can Nonmelanoma Skin Cancer Be Prevented? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_2X_Can_skin_cancer_be_ prevented_51.asp?sitearea=&level= Safer Sunning in Seven Steps http://www.fda.gov/opacom/lowlit/sunsafty.pdf Skin Cancer (PDQ): Prevention Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/prevention/skin/patient/ Skin Cancer (PDQ): Screening Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/screening/skin/patient/ What Are the Risk Factors for Nonmelanoma Skin Cancer? Source: American Cancer Society http://www.cancer.org/docroot/CRI/content/CRI_2_4_2X_What_are_the_risk_fa ctors_for_skin_cancer_51.asp?sitearea=
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Research Long-Standing Studies Support UVB Radiation Is a Leading Cause of Skin Cancer Source: American Academy of Dermatology http://www.aad.org/PressReleases/UVBRadiation.html Sunning for Science: The Effects of Common Substances on Sun-Exposed Skin Source: Food and Drug Administration http://www.fda.gov/fdac/features/2002/602_sun.html What's New in Nonmelanoma Skin Cancer Research and Treatment? Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_6x_whats_new_in_skin_canc er_research_and_treatment_51.asp?sitearea=cri
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Statistics 2003 Skin Cancer Fact Sheet Source: American Academy of Dermatology http://www.aad.org/SkinCancerNews/WhatIsSkinCancer/SCancerFacts.html Facts and Statistics about Skin Cancer Source: National Center for Chronic Disease Prevention and Health Promotion http://www.cdc.gov/chooseyourcover/skin.htm What Are the Key Statistics for Nonmelanoma Skin Cancer Source: American Cancer Society http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_are_the_key_statist ics_for_skin_cancer_51.asp?sitearea=cri
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Teenagers Skin Cancer: The Burden of Skin Cancer Source: Centers for Disease Control and Prevention http://www.cdc.gov/nccdphp/dash/skincancer/guidelines/facts.htm Tanning Taboo Source: Nemours Foundation http://kidshealth.org/teen/safety/safebasics/tanning.html
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 skin cancer. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general 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: •
What You Need to Know About Skin Cancer Source: Bethesda, MD, US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute, 25 p., Revised April 1993. Contact: US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute, Office of Cancer Communications, Building 31, Room 10A24, 9000 Rockville Pike, Bethesda, MD 20892. (800) 4-CANCER. Summary: What You Need to Know About Skin Cancer is a brochure that explains the diagnosis, treatment, and prevention of skin cancer. Contents include (1) a description of the structure of the skin; (2) a general definition of cancer; (3) types of skin cancer (basal cell carcinoma, squamous cell carcinoma, and melanoma); (4) cause and prevention of skin cancer (risk factors such as ultraviolet radiation (UV) exposure, tanning booths, and use of sunscreens); (5) symptoms of skin cancer (with color photographs for illustration); (6) detection and diagnosis of skin cancer (physical examinations and biopsy); (7) treatment planning (obtaining a second opinion); and (8) methods used in treating skin cancer (surgery, curettage and eletrodessication, Mohs' surgery, cryosurgery, laser therapy, grafting, radiation, topical chemotherapy, clinical trials, and followup care). Also included are questions to ask the doctor, a brief section on skin cancer research, a glossary of medical terms, a list of resources from the National Cancer Institute (NCI) and other organizations, and a diagram of how to do a skin self examination.
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Skin Cancer: If You Can Spot It, You Can Stop It Source: New York, NY, Skin Cancer Foundation, 7 pages and 1-fold map, 1992. Contact: Skin Cancer Foundation, Box 561, New York, NY 10156. Summary: Skin Cancer: If You Can Spot It, You Can Stop It is a patient education brochure on skin self examination. It explains why a self-examination is so important, who should do it, when to do it, what to look for, and the warning signs of skin cancer. Diagrams accompany a step-by-step self-examination explained by short paragraphs. Fold-out body maps are included, with a measurement guide to the size of growths (from 3 mm to 15 mm) and explanations for their use in charting what the patient finds on his or her own body. Skin self-examination is recommended for every 3 months, and a schedule is provided to mark when the reader performs it (the schedule covers 5 years). If what looks like skin cancer is seen, the reader is told not to delay and not to overlook it; the need to see a physician is emphasized. Protection is also emphasized: Sunlight is responsible for over 90 percent of all skin cancers, and everyone should practice sun-protection habits such as staying indoors when the sun is brightest, using a sunscreen rated sun protection factor (SPF) 15 or higher, and never deliberately seeking a tan from either the sun or artificial sources.
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Guide to Skin Cancers and Precancers, A Source: New York, NY: Skin Cancer Foundation. 2002. 18 p. Contact: Available from Skin Cancer Foundation. Box 561, New York, NY 10156. (212) 725-5176. Fax (212) 725-5751. E-mail:
[email protected]. Website: www.skincancer.org. PRICE: Contact for current pricing; bulk orders available. Item No. BR-19. Summary: This booklet provides the general public with information on skin precancers and cancers. Actinic keratosis (AK), or solar keratosis, is the most common type of precancerous skin lesion. AKs most often appear on skin surfaces that have been frequently exposed to the sun or to artificial sources of ultraviolet light. They range in size from 1 millimeter to 1 inch in diameter. AKs usually appear as small crusty, scaly, or crumbly bumps or horns that are dry and rough to the touch. Untreated AKs may develop into squamous cell carcinoma (SCC). Treatment options for AKs include cryosurgery; curettage and desiccation; topical medications such as 5-fluorouracil cream or solution, hyaluronic acid/diclofenac, and imiquimod cream; chemical peeling; laser surgery; and photodynamic therapy. The most common skin cancers are basal cell carcinoma (BCC) and SCC. Both are mainly caused by long term sun exposure, so they typically occur in areas that are exposed to the sun. Although BCCs rarely spread to vital organs, they can lead to disfigurement. SCCs have a greater chance of spreading and becoming life threatening if untreated. Treatment options for BCCs and SCCs include curettage and electrodesiccation, excisional surgery, radiation, and Mohs micrographic surgery. In addition, cryosurgery, laser surgery, and photodynamic therapy can be used to treat BCCs and SCCs. The deadliest form of skin cancer is melanoma. It is most often caused by intense, intermittent exposure to the sun, especially before age 18. Melanoma is treatable in its earliest stage, but if left untreated, it will spread to vital organs. People should check their skin every month for lesions that are asymmetrical and have border irregularity, color variability, and a diameter larger than a pencil eraser. Treatment options for melanoma discovered at an early stage include excisional surgery, Mohs micrographic surgery, and regional lymph node dissection. Approaches for treating melanoma that has spread include radiation,
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chemotherapy, and immunotherapy. Skin cancers can be prevented by taking appropriate sun safety measures. 18 figures. •
Skin Cancer Source: American Academy of Dermatology. 2001. 8 p. Contact: Available from American Academy of Dermatology. 930 N. Meacham Road, P.O. Box 4014, Schaumberg, IL 60168-4014. (888)462-DERM x22. Website: www.add.org. PRICE: single copy free; bulk prices available. Summary: This brochure provides patients with tips on avoiding overexposure to the sun, the most common cause of skin cancer, identifying melanomas, and delineating the forms of skin cancer. To prevent overexposure to ultraviolet rays, people should avoid direct sunlight between 10 AM and 4 PM, wear protective clothing and wide-brimmed hats, and apply sunscreens with an SPF of 15 or higher. Moles that are asymmetric, have irregular borders, are mottled in color, or have a diameter greater than 6 millimeters should be brought to the attention of the patient's physician as they are usually curable when caught early. Diagrams for a full body examination are presented. Actinic keratoses are small, red, scaly spots on the face, lower arms, and hands that may develop into skin cancer if left untreated. Basal cell carcinoma appear as a small fleshy lump on the head, neck, hands or trunk and is most common in fair-skinned people. It metastasizes slowly. Squamous cell carcinoma also appears as a bump or scaly red patch and is found on the rim of the ear, lips, face or mouth, generally in fair skinned people, and does metastasize. Both basal cell and squamous cell cancers are 95 percent curable when identified early and treated by dermatologic surgery. Malignant melanoma is the deadliest form of skin cancer, often appears without warning, and spreads quickly. Warning signs include changes in the surface of a mole, oozing, bleeding, itchiness, tenderness, and pain. A skin biopsy can determine if the area is cancerous, and if so, surgery is performed to remove the cancer.
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What Everyone Should Know About Skin Cancer Source: South Deerfield, MA: Channing L. Bete Co., Inc. 1999. 16 p. Contact: Available from Channing L. Bete Co., Inc. 200 State Road, South Deerfield, MA 01373-0200. (800) 628-7733. Fax (800) 499-6464. E-mail:
[email protected]. PRICE: Contact company for pricing information; available in bulk. Order Number 37259C-6-96. Summary: This illustrated booklet provides the general public with information on skin cancer. This most common form of all cancers results from the uncontrolled growth of abnormal skin cells. It is usually preventable and curable. Types of skin cancer include basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. Overexposure to the sun causes most cases of skin cancer. Although anyone can get skin cancer, people with certain physical traits and lifestyles are at greater risk. Being alert to changes in the skin's color, texture, and sensation and performing a monthly skin examination are important early detection measures. Treatment methods include excisional surgery, cryosurgery, radiation therapy, topical treatments, electrosurgery, chemotherapy, Mohs surgery, and reconstructive surgery. The booklet provides tips on preventing skin cancer, answers questions about the disease, and presents sources of additional information.
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Skin Cancer: An Undeclared Epidemic Source: Schaumburg, IL: American Academy of Dermatology. 1994. 8 p. Contact: Available from American Academy of Dermatology. P.O. Box 681069, Schaumburg, IL 60168-1069. (888) 462-3376 or (847) 330-0230. http://www.aad.org/index.html. PRICE: Single copy free; bulk prices available. Summary: This brochure for the general public provides information on skin cancer. It states that overexposure to sunlight is almost universally accepted by medical experts as the main cause of skin cancer and that guarding the skin against the known causes is the best prevention. The brochure suggests a method of self-examination to detect any skin changes that will ensure that all areas of the body are examined. It describes the features of actinic keratosis, a precancerous condition, as well as basal and squamous cell carcinoma and malignant melanoma. In addition, the brochure comments on various skin cancer treatments. 2 figures. 3 photographs.
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Skin Cancer Risks From Psoriasis Treatments Source: Portland, OR: National Psoriasis Foundation. 1994. 8 p. Contact: Available from National Psoriasis Foundation. P.O. Box 9009, Portland, OR 97207-9009. (800) 723-9166 Ext. 12 or (503) 244-7404. Fax (503) 245-0626. E-mail:
[email protected]. Website: www.psoriasis.org. PRICE: $0.35 each plus shipping and handling; bulk orders available. Summary: This pamphlet provides people who have psoriasis with information on the risk of skin cancer from common treatments. Treatments with the potential to increase the risk of skin cancer are exposing the skin to ultraviolet light B (UVB) or ultraviolet light A plus the drug psoralen (PUVA). Although UVB is an established carcinogen, long-term studies indicate that it is relatively safe at the low doses used for UVB phototherapy. Even for people treated with high levels of UVB, there seems to be little or no increased risk of skin cancer. The risk from PUVA is complicated by various environmental and genetic factors. Although PUVA has been identified as a carcinogen, the risk depends on the total dose. If there are no other complications, the risk becomes significant after a cumulative dose of over 150 to 160 treatments. Nonmelanoma skin cancers, such as basal cell carcinoma and squamous cell carcinoma, are the types directly associated with phototherapy. Actinic keratoses are precancerous lesions caused by overexposure to ultraviolet light. A type of skin damage known as photoaging may also occur from long-term exposure to ultraviolet light. The pamphlet describes the features of these skin conditions, and offers recommendations on using phototherapy, and concludes with information on the National Psoriasis Foundation.
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Squamous Cell Carcinoma: The Second Most Common Skin Cancer Source: New York, NY: Skin Cancer Foundation. 1990. 12 p. Contact: Available from Skin Cancer Foundation. 245 Fifth Avenue, Suite 1403, New York, NY 10016. (212) 725-5176. Fax (212) 725-5751. E-mail:
[email protected]. PRICE: Single copy free; bulk orders available at cost. Summary: This brochure provides the general public with information on squamous cell carcinoma, the second most common form of skin cancer. Most cases of squamous cell carcinoma are caused by chronic exposure to sunlight, so they most frequently appear on sun-exposed parts of the body. They may also occur where the skin has suffered certain kinds of injury. People with a history of exposure to the sun can develop
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squamous cell carcinoma; however, those who are at highest risk have fair skin, light hair, and blue, green, or gray eyes. People who work outdoors or spend leisure time in the sun are particularly susceptible. The pamphlet highlights certain precursor conditions that are sometimes associated with later development of squamous cell carcinoma, including actinic keratosis, actinic cheilitis, leukoplakia, and Bowen's disease. In addition, the pamphlet describes the features of squamous cell carcinomas, as well as surgical and other methods of eradicating them, and discusses the possibility of recurrence. 6 figures. •
Types and Descriptions of Skin Cancers Source: New York, NY: Skin Cancer Foundation. 199x. 6 p. Contact: Available from Skin Cancer Foundation. 245 Fifth Avenue, Suite 1403, New York, NY 10016. (212) 725-5176. Fax (212) 725-5751. E-mail:
[email protected]. PRICE: Single copy free; bulk orders available at cost. Summary: This pamphlet uses photographs and descriptive text to provide the general public with information about the features of basal and squamous cell carcinoma and malignant melanoma. Basal cell carcinomas, which are raised, translucent, pearly nodules that may crust, ulcerate, and sometimes bleed, usually occur on the face and other exposed areas of the body. Squamous cell carcinomas, which are usually raised, pink, opaque nodules or patches that frequently ulcerate in the center, most often appear on exposed areas of the body. Malignant melanomas, which are usually small brown-black or larger multicolored patches, plaques, or nodules with irregular borders, may arise in preexisting moles. In addition, the pamphlet provides examples of various precancers, including actinic keratoses, leukoplakia, and radiodermatitis. 9 figures.
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It's Never Too Early To Stop Skin Cancer Source: New York, NY: Skin Cancer Foundation. 199x. 6 p. Contact: Available from Skin Cancer Foundation. Box 561, New York, NY 10156. (212) 725-5176. Fax (212) 725-5751. E-mail:
[email protected]. Website: www.skincancer.org. PRICE: Contact for current pricing; bulk orders available. Item No. BR-2. Summary: This pamphlet uses a question and answer format to provide the general public with information on skin cancer. The three main types of skin cancer are basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. Exposure to the ultraviolet rays of the sun is the most frequent cause of skin cancer. People at risk of developing skin cancer are those who have fair skin and those who allow themselves considerable exposure to the sun. Skin cancer in its earliest stages may appear as a discoloration of the skin. People should pay attention to any changes in the size, color, shape, or thickness of preexisting moles or other growths. A biopsy of a suspicious lesion helps a doctor determine whether the lesion is benign, precancerous, or cancerous. Common treatment methods are electrosurgery, excisional surgery, chemosurgery, cryosurgery, radiation therapy, and chemotherapy. Protective measures include avoiding unnecessary exposure to the sun; wearing tightly woven protective clothing such as sun hats, long sleeved shirts, pants, and gloves; avoiding midday exposure; and using sunscreen with a sun protection factor (SPF) of 15 or higher. The pamphlet explains what the SPF is and how to select and use sunscreen.
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Skin Cancer: Reduce Your Risk With 'Safe-Sun' Guidelines Source: American Academy of Family Physicians. 2002. 3 p. Contact: Available from American Academy of Family Physicians. Website: www.familydoctor.org. Summary: This fact sheet provides guidelines for protecting the skin from sun damage and skin cancer. To prevent skin damage and cancer: avoid the sun during 10 a.m and 4 p.m (when it is strongest); use a sunscreen with an SPF of 15 or greater, applying it every half hour and after swimming or sweating; keep as much of the skin covered as possible, including a wide-brimmed hat and sunglasses; and do not use tanning booths. In addition, check your skin once a month for new moles or changes in older moles as this might indicate a skin cancer.
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Preventing Skin Cancer Source: Patient Care. 33(9): 63. May 15, 1999. Summary: This patient information sheet provides people with general information on preventing skin cancer. The information sheet presents a self-assessment quiz to help people determine whether they are at risk for skin cancer, lists myths and facts about it, provides sun safety tips, and identifies resources.
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Treatment of Skin Cancer Source: Schaumburg, IL: American Society for Dermatologic Surgery (ASDS). 1996. 1 p. Contact: Available from American Society for Dermatologic Surgery. 930 North Meacham Road, Schaumburg, IL 60173-6016. (800) 441-2737 or (847) 330-9830. Fax (847) 330-0050. Website: www.asds-net.org. PRICE: Call '800' number or access website for single free copy. Summary: This fact sheet provides people who have skin cancer with information on its treatment. Skin cancer is the uncontrollable growth of abnormal cells in a layer of skin; the type depends on the cells affected. The three most common forms are basal and squamous cell carcinoma and malignant melanoma. A dermatologic surgeon uses various procedures and techniques to treat skin cancer, including curettage, surgical excision, cryosurgery, topical chemotherapy, MOHS micrographic surgery, and laser surgery. The fact sheet provides information on the American Society for Dermatologic Surgery and presents a source for further information.
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Skin Cancer: Preventing America's Most Common Cancer Source: Atlanta, GA, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 4 p., 2001. Contact: National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, 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/nscpep/skinpdfs/sknaag01.pdf;
[email protected]. Summary: Skin Cancer: Preventing America's Most Common Cancer describes efforts to prevent skin cancer by educating people about the preventive measures that can be taken. Skin cancer is the most common form of cancer in the United States. The major types of skin cancer are the highly curable basal cell and squamous cell carcinomas and the more serious malignant melanoma. Risk factors for skin cancer include (1) fair to
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light skin complexion, (2) family history of skin cancer, (3) chronic exposure to the sun, (4) personal history of skin cancer, (5) history of sunburns in early life, (6) atypical moles, (7) a large number of moles, and (8) freckles. Skin cancer is largely preventable when sun protection measures are consistently used. Parents, health care providers, schools, and community organizations can play a major role in reinforcing sun protection behaviors and changing attitudes about exposure to the sun. The Centers for Disease Control and Prevention (CDC) develops epidemiologic research and monitoring systems to determine national trends in sun protection behaviors and attitudes about sun exposure. Findings are being used to better target and evaluate skin cancer prevention efforts. CDC's national Choose Your Cover media campaign helps states increase awareness about skin cancer and its causes as well as influence social norms regarding sun protection and tanned skin. CDC has convened the National Council on Skin Cancer Prevention, an alliance of organizations with common goals to (1) increase awareness and prevention behaviors, (2) develop and support partnerships to extend and reinforce core messages for behavior change, (3) coordinate nationwide efforts, and (4) develop a national skin cancer prevention and education plan. CDC currently funds four skin cancer prevention demonstration projects: (1) Pool Cool; (2) Sunwise Stampede; (3) National Coalition for Skin Cancer Prevention in Health, Physical Education, Recreation, and Youth Sports; and (4) Coalition for Skin Cancer Prevention in Maryland. •
Preventing Skin Cancer: The Nation's Most Common Cancer: At-a-Glance 2000 Source: Atlanta, GA, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 4 p., 2000. Contact: National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Mail Stop K-64, 4770 Buford Highway NE., Atlanta, GA 30341-3717. (770) 488-4751, (888) 842-6355. FAX: (770) 488-4760. INTERNET/EMAIL:
[email protected]. http://www.cdc.gov/cancer/nscpep/skin.htm. Summary: Preventing Skin Cancer: The Nation's Most Common Cancer: At-a-Glance 2000 describes efforts to prevent skin cancer. It is vital to educate young people to develop healthy sun behaviors now that will help them avoid developing skin cancer later. Skin cancer is the most common form of cancer in the United States. The three major types of skin cancer are the highly-curable (1) basal and (2) squamous cell carcinomas, and (3) the more serious malignant melanoma. Malignant melanoma, the most rapidly increasing form of cancer in the United States, causes more than 75 percent of all deaths from skin cancer. Risk factors for skin cancer are (1) fair to light skin complexion, (2) family history of skin cancer, (3) personal history of skin cancer, (4) chronic exposure to the sun, (5) history of sunburns early in life, (6) atypical moles, (7) a large number of moles, and (8) freckles (an indicator of sun sensitivity and sun damage). Skin cancer is largely preventable when sun protection measures are consistently used. Measures include (1) seeking shade, (2) wearing protective clothing when exposed to sunlight, and (3) routinely using sunscreen lotion. Launched in 1998, the Centers for Disease Control and Prevention's (CDC's) national skin cancer prevention campaign, Choose Your Cover, is designed to change social norms by promoting the acceptability of behaviors to protect skin and the desirability of skin that is free of the damaging effects of sun exposure. CDC has convened the National Council on Skin Cancer Prevention to facilitate national skin cancer awareness and prevention efforts. The Council has the following objectives: (1) To increase skin cancer awareness and prevention behaviors among all populations, with special emphasis on populations at high risk; (2) to develop and support partnerships to extend and reinforce core messages
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for behavior change; (3) to coordinate a public health response to nationwide efforts to reduce skin cancer incidence and deaths; and (4) to develop a national skin cancer prevention and education plan. •
Many Faces of Malignant Melanoma, The Source: New York, NY: Skin Cancer Foundation. 199x. 6 p. Contact: Available from Skin Cancer Foundation. Box 561, New York, NY 10156. (212) 725-5176. Fax (212) 725-5751. E-mail:
[email protected]. Website: www.skincancer.org. PRICE: Contact for current pricing; bulk orders available. Item No. BR-5. Summary: This pamphlet provides health professionals and the general public with 24 examples of malignant melanoma, which were selected to represent thin, intermediate, and thick melanomas. Tumor thickness is a key indicator in predicting which malignant melanomas are curable and which are not. Malignant melanomas that are removed when they are less than three fourths of a millimeter thick are cured in almost all cases; however, progressively thicker malignant melanomas have correspondingly poorer prognoses. The first eight photographs show examples of thin, early malignant melanomas. The second eight photographs depict examples of melanomas of intermediate thickness. The final eight photographs show examples of the thickest melanomas. The pamphlet also includes a list of the risk factors for and warning signs of malignant melanoma. 24 figures.
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Melanoma of the Skin in Pennsylvania Source: Harrisburg, PA, Pennsylvania Department of Health, 2 p., 2001. Contact: Pennsylvania Department of Health, Bureau 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/stats/. Summary: Melanoma of the Skin in Pennsylvania describes the incidence, mortality, stage of disease at time of diagnosis, and risk factors for melanoma among Pennsylvania residents. Annual age-adjusted incidence rates for invasive melanoma have been increasing, especially since 1994. Most cases occur among whites, and excess exposure to sunlight is a major risk factor. Pennsylvania's age-adjusted incidence rates for melanoma for 1998 were 28 percent lower for all cases, 25 percent lower for males, and 30 percent lower for females than comparable national rates. The annual age-adjusted mortality rates for melanoma remained relatively unchanged between 1989 and 1999, but Pennsylvania's rates were slightly higher than national rates. Early stage of disease at time of diagnosis of melanoma for all cases in Pennsylvania increased from 9.8 percent in 1988 to 26.9 percent in 1998. The most dramatic increase in early-stage diagnoses was among males. Exposure of skin to sunlight, especially among those with fair skin, is a well-known risk factor for melanoma. According to results from the Pennsylvania Behavioral Risk Factor Surveillance System, (1) 36 percent of females and 21 percent of males age 18 years and older said that they always or often use sunscreen when outdoors for 1 hour or longer, and (2) 52 percent of females and 40 percent of males always or often stay in the shade on sunny days.
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Prevention and Early Detection of Malignant Melanoma Source: Atlanta, GA, American Cancer Society, 8 p., 1995.
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Contact: American Cancer Society, 1599 Clifton Road, NE., Atlanta, GA 30329-4251. Publication no. 90-50M-Rev. 10/95-No. 3029. Summary: Prevention and Early Detection of Malignant Melanoma, a brochure for physicians and nurses, describes the characteristics, symptoms, and risk factors of malignant melanoma. Even though the rate of malignant melanoma in the United States has increased approximately 80 percent over the last 15 years, and 1,500 percent over the last 50 years, early malignant melanoma is highly curable. The greatest increase in incidence has taken place among men, particularly those over age 65 years. Before age 40 years, melanoma occurs more frequently among women than among men. In addition to age and gender, high risk is associated with having fair skin, light hair, light eyes, and the genetic phenotype most susceptible to sunburn. Data indicate that the risk of developing melanoma is specifically related to the amount and intensity of sun exposure received during adolescence. Dysplastic nevi are potential precursors of melanoma and markers for increased risk of developing melanoma. People with dysplastic nevi, who make up 4 percent of the population, have an approximately 6-fold risk of developing melanoma. People with dysplastic nevi and a personal or family history of melanoma have an even higher risk of developing melanoma. The ABCD Rule for Early Detection is a guide to the characteristic features of malignant melanoma that can assist the physician or nurse in identifying suspicious skin lesions: A stands for asymmetry (melanomas tend to be asymmetric), B refers to border (melanoma usually have a notched, irregular, or indistinct border), C is for color (early melanomas have an uneven color), D stands for diameter (most melanomas have a diameter greater than 6 millimeters). Changes in color, size, shape, elevation, surface, surrounding skin, sensation, and consistency may also indicate malignant melanoma. The acronym WAR summarizes preventive measures physicians and nurses can teach their patients to follow to reduce their risk of developing malignant melanoma: Wear protective clothing, Apply sunscreen, and Refrain from sun exposure during the middle of the day. Primary care physicians and nurses have a vital role to play in preventing needless suffering and death from malignant melanoma. •
What You Need to Know About Melanoma Source: Bethesda, MD, US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute, 33 p., Revised April 1993. Contact: US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute, Office of Cancer Communications, Building 31, Room 10A24, 9000 Rockville Pike, Bethesda, MD 20892. (800) 4-CANCER. Summary: What You Need to Know About Melanoma, a booklet by the National Cancer Institute, explains the importance of detecting melanoma, a type of skin cancer, as early as possible; treatment will likely be most effective when the tumor is thin and has not deeply invaded the skin or spread to other parts of the body. Intended for the general population, the brochure describes the signs and symptoms, early detection, diagnosis, treatment, possible side effects of treatment, and followup care for melanoma. Melanoma occurs when skin cells called melanocytes become malignant; while it can occur on any skin surface, melanoma is often found in men on the trunk or the head and neck, and often develops in women on the lower legs or the trunk. Though rare in African Americans and others with dark skin, melanoma tends to occur in dark-skinned people under the fingernails or toenails or on the palms and soles. Melanoma affects people of all ages, but chances increase with age. Other factors increasing a person's risk of developing melanoma include two or more close relatives who have had the disease;
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the presence of atypical moles called dysplastic nevi; and one or more severe, blistering sunburns as a child or teenager. First signs often involve a change in the size, shape, color or texture of an existing mole, or the appearance of a new, abnormal mole. The brochure recommends that physicians check their patients' skin during routine physical examinations, and that people check their own skin regularly for new growths or other changes and to report them to the physician without delay. A 5-step pictorial guide on how to perform a skin self-examination is presented. If melanoma is suspected, the patient requires a biopsy for a definite diagnosis; if melanoma is found, the physician determines the extent, or stage, of the disease. While surgery is the standard treatment for melanoma, physicians may use chemotherapy, biological therapy or radiation therapy, alone or in combination, to control melanoma that has spread to other parts of the body. Recommendations to help prevent melanoma include avoiding exposure to the midday sun whenever possible; wearing a hat and long sleeves outdoors; and applying lotions or creams containing sunscreens, for protection. •
Malignant Melanoma Source: Schaumburg, IL: American Academy of Dermatology (AAD). 2001. 8 p. Contact: Available from American Academy of Dermatology, Marketing Department. P.O. Box 2289, Carol Stream, IL 60132-2289. (847) 240-1280. Fax (847) 240-1859. E-mail:
[email protected]. Website: www.aad.org. PRICE: Single copy free; bulk prices available. Summary: This pamphlet uses a question and answer format to provide people who have melanoma with information on its causes, symptoms, and treatment. Melanoma is a cancer of the pigment producing cells in the skin. Although it is uncertain how all cases of melanoma develop, it is clear that excessive sun exposure, especially blistering sunburns during childhood, can promote melanoma development. Ultraviolet radiation used in indoor tanning equipment may also cause melanoma. Although anyone can get melanoma, fair skinned people who tan poorly or burn easily are at greater risk. Other risk factors include a history of sunburns, many moles, atypical moles, and close relatives who had melanoma. Melanoma usually begins on the surface of the skin where it is easily treated. Left untreated, it can grow down into the skin, ultimately reaching the blood and lymphatic vessels and spreading around the body. Melanoma is usually brown or black in color, but may be red, skin colored, or white. Melanomas slowly get larger. Diagnosis is based on a biopsy of the lesion for examination under the microscope. Treatment begins with surgical removal of the melanoma and some normal appearing skin around the growth. The depth of invasion of the growth into the skin guides further treatment. Preventive efforts include avoiding sun exposure during times of the day when the sun is the strongest, wearing a broad spectrum sunscreen and protective clothing, and performing a monthly self examination. The pamphlet includes the asymmetry, border irregularity, color, and diameter (ABCD) rules to determine if a spot on the skin is suspicious. 5 figures.
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Dysplastic Nevi and Malignant Melanoma: A Patient's Guide Source: New York, NY: Skin Cancer Foundation. 1997. 12 p. Contact: Available from Skin Cancer Foundation. 245 Fifth Avenue, Suite 1403, New York, NY 10016. (212) 725-5176. Fax (212) 725-5751. E-mail:
[email protected]. PRICE: Single copy free; bulk orders available at cost. Summary: This brochure provides people who have dysplastic nevi and malignant melanoma with information on recognizing the features of these skin disorders.
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Dysplastic nevi are unusual moles that are markers for an increased risk of melanoma, which is a form of skin cancer that often looks like an irregular, enlarging, or inflamed mole. The brochure compares the features of normal moles with those of dysplastic nevi and explains what happens if moles become malignant melanoma. The brochure also offers guidelines for people who have an increased risk of developing melanoma or a diagnosis of dysplastic nevus, including performing a monthly skin self-examination, having an annual medical examination, and avoiding or decreasing exposure to the sun. 13 figures. •
ABCDs of Moles and Melanomas, The Source: New York, NY: Skin Cancer Foundation. 199x. 6 p. Contact: Available from Skin Cancer Foundation. Box 561, New York, NY 10156. (212) 725-5176. Fax (212) 725-5751. E-mail:
[email protected]. Website: www.skincancer.org. PRICE: Contact for current pricing; bulk orders available. Item No. BR-4. Summary: This pamphlet provides the general public with information on the detection of malignant melanoma. A change in a mole or other spot on the skin may be the first sign of an early malignant melanoma or other form of skin cancer. Malignant melanoma arises in moles or in the tanning cells of the skin. People at high risk of developing malignant melanoma are those who have a family history of the disease, a previous melanoma, unusual moles on the skin, fair skin, light hair and eye color, a record of painful or blistering sunburns, and indoor occupations and outdoor recreational habits. Regular self examination is the best way to detect a malignant melanoma. Some forms of early malignant melanoma are asymmetrical, have uneven borders, are multicolored, and are larger than a pencil eraser. The pamphlet provides examples of these features. 12 figures.
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Melanoma Source: Kirksville, MO: American Osteopathic College of Dermatology (AOCD). 2001. 2 p. Contact: Available online from American Osteopathic College of Dermatology. 1501 East Illinois Street, P.O. Box 7525, Kirksville, MO 63501. (800) 449-2623 or (660) 665-2184. Fax (660) 627-2623. E-mail:
[email protected]. Website: www.aocd.org/skin/dermatologic_diseases/ index.html. Summary: This fact sheet provides people who have melanoma with information on this form of skin cancer. Melanoma, which grows from the melanocytes (the cells that color and tan the skin), often will spread to other parts of the body through the lymphatic system or the bloodstream. The disease can appear on the body as a new mole; as a mole that has changed in size, shape, feeling, or color; or as a mole that has developed oozing or bleeding. Most melanomas are dark, but they may be flesh colored or pink to red. If there is a serious question of skin cancer, the mole or pigmented area will be surgically removed. A laboratory will analyze the removed skin. If melanoma is diagnosed, a physical examination and laboratory tests will be done to look for signs that it has spread to other parts of the body. In the earliest melanoma, the abnormal cells are found only in the outer layer of skin cells. Melanomas are more advanced if they go deeper than 4 millimeters into the skin. Those that have spread are very serious. Surgery is the main treatment of all stages of melanoma. The biopsy site and a rim of seemingly normal skin are removed. Treatment of advanced melanoma may involve surgical removal of the tumor and any affected lymph nodes, followed by systemic or local
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mono or multiple chemotherapy. Melanoma vaccines are a promising new treatment for advanced melanoma. 3 figures. •
Many Faces of Melanoma Source: New York, NY, Skin Cancer Foundation, 6 p., 1996. Contact: Skin Cancer Foundation, Box 561, New York, NY 10156. Summary: The Many Faces of Melanoma is designed to help those in the medical profession and in the general public identify individuals at high risk for melanoma. It notes that it is now possible to predict with considerable accuracy which malignant melanomas are curable and which are not. Thickness of the tumor is a key indicator of prognosis. Melanomas that are removed when they are less that 3/4 of a millimeter in thickness are cured in virtually all cases, as long-term followup has repeatedly confirmed. Progressively thicker melanomas, however, have correspondingly poorer prognoses. The fact sheet presents 24 photographs that depict malignant melanomas in three ranges of thickness: (1) Thin, (2) intermediate, and (3) thick. It also summarizes the warning signs of melanoma and melanoma risk factors.
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Basal Cell Carcinoma Source: Schaumburg, IL: American Academy of Dermatology (AAD). 2001. 8 p. Contact: Available from American Academy of Dermatology, Marketing Department. P.O. Box 2289, Carol Stream, IL 60132-2289. (847) 240-1280. Fax (847) 240-1859. E-mail:
[email protected]. Website: www.aad.org. PRICE: Single copy free; bulk prices available. Summary: This pamphlet uses a question and answer format to provide people who have basal cell carcinoma with information on the etiology, features, diagnosis, treatment, and prevention of this common skin cancer. Basal cell cancer does not metastasize or travel in the bloodstream to other organs. Most cases are believed to be caused by exposure to the harmful ultraviolet rays of the sun, and basal cell cancer most often appears on sun exposed areas. Basal cell tumors have several different forms, with the most common being a small dome shaped bump that has a pearly white color. Other presentations include a pimple like growth that heals but recurs or a smooth white or yellowish waxy scar. A very common sign of basal cell cancer is a sore that bleeds and heals up but recurs. Diagnosis is based on the results of a biopsy of the growth. Surgical options for removing the growth include electrodesiccation and curettage and simple surgical excision. Other treatments, such as cryosurgery, radiation therapy, and laser surgery, may be used in certain situations. Cosmetic outcomes following surgery are usually excellent. Untreated basal cell cancer will continue to grow locally and may cause serious problems if it is located near the eyes, ears, nose, or other important organs. People who have had one basal cell cancer are at a 40 percent risk of getting a second basal cell cancer within 5 years, and people who have had multiple basal cell cancers or other skin cancers are at an increased risk for melanoma. Proper sun protection may help prevent the development of further basal cell cancers. 4 figures.
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Basal Cell Carcinoma: The Most Common Cancer Source: New York, NY: Skin Cancer Foundation. 1995. 6 p. Contact: Available from Skin Cancer Foundation. 245 Fifth Avenue, Suite 1403, New York, NY 10016. (212) 725-5176. Fax (212) 725-5751. E-mail:
[email protected]. PRICE: Single copy free; bulk orders available at cost.
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Summary: This pamphlet provides the general public with information about basal cell carcinoma, which is the most common of all cancers and is caused mainly by overexposure to sunlight. People who have a history of exposure to the sun can develop basal cell carcinoma; however, those who are at highest risk have fair skin, light hair, and blue, green, or gray eyes. People who work outdoors or spend leisure time in the sun are particularly susceptible. The pamphlet identifies the warning signs of basal cell carcinoma, including a persistent, nonhealing sore; an reddish patch that may crust; a smooth growth with an elevated, rolled border and an indentation in the center; a shiny bump that is pearly or translucent; and a scar-like area that often has poorly defined borders. In addition, the pamphlet briefly describes surgical and other methods for eradicating basal cell carcinoma and discusses the possibility of recurrence. 10 figures. •
NBCCS Support Network: For People Living and Coping with Nevoid Basal Cell Carcinoma Syndrome, Their Families, Health Care Professionals, and Others Who Care Source: Burtonsvile, MD: NBCCS Support Network. 2 p. Contact: Available from NBCCS Support Network. 3902 Greencastle Ridge Drive, Number 204, Burtonsville, MD 20866. (800) 264-8099 or (800) 815-4447. PRICE: Single copy free. Summary: This brochure describes the NBCCS Support Network, an organization formed to address the medical and psychosocial concerns of persons with nevoid basal cell carcinoma syndrome (NBCCS). The brochure first describes NBCCS and its treatments, then explains the NBCCS mission statement and how the Support Network operates. The brochure also includes a information form with which readers can get on the NBCCS mailing list, as well as a list of the NBCCS Support Network's medical advisory board members. A toll-free telephone number is also provided. 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 “skin cancer” (or synonyms). The following was recently posted: •
Guidelines for school programs to prevent skin cancer Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2002 April 26; 18 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3219&nbr=2445&a mp;string=skin+AND+cancer
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Guidelines of care for primary cutaneous melanoma Source: American Academy of Dermatology - Medical Specialty Society; 2001 March; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2741&nbr=1967&a mp;string=melanoma
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Screening for skin cancer Source: American College of Preventive Medicine - Medical Specialty Society; 1998; 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1309&nbr=558&am p;string=skin+AND+cancer
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Screening for skin cancer: recommendations and rationale Source: United States Preventive Services Task Force - Independent Expert Panel; 1996 (revised 2001 Apr); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2662&nbr=1888&a mp;string=skin+AND+cancer
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Skin cancer Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3391&nbr=2617&a mp;string=skin+AND+cancer
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Systemic adjuvant therapy for patients at high risk for recurrent melanoma Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 1998 May 27 (updated 2002 Nov); 32 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3535&nbr=2761&a mp;string=melanoma 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: •
ABCD’s of Skin Cancer Summary: A general overview of three types of skin cancer-- basal cell carcinoma, squamous cell carcinoma, and melanoma are illustrated. Explains self-exam for skin cancer. Source: American Academy of Dermatology http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5777
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Cancer Prevention and Control Page - Centers for Disease Control and Prevention Summary: Prevention control resources that focus on the National Breast and Cervical Cancer Early Detection Program, the National Program of Cancer Registries, the National Skin Cancer Prevention Education Source: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=252
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Choose Your Cover Campaign - Skin Cancer Prevention Summary: This is a national, multi-year skin cancer prevention initiative, the goal of which is to educate and encourage people to protect themselves from the sun's ultraviolet rays by practicing sun-safe Source: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2738
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Congenital Nevi or Moles Summary: This information is intended to provide basic information only. It provides a general description for nevi and discusses the risk of skin cancer/melanoma associated with them. Source: Nevus Network http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2357
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National Cancer Data Summary: This page links to national cancer data about cancer registries, special populations, and breast, cervical, colorectal, ovarian, prostate, and skin cancer. Source: National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7176
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Preventing Skin Cancer: The Nation's Most Common Cancer AT-A-GLANCE Summary: A summary of the efforts and services related to this national skin cancer prevention program designed to educate young people to develop healthy sun behaviors that will decrease the risk for Source: Division of Cancer Prevention and Control, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4708
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Protecting Kids From the Sun Summary: This online document gives details on the application of sunscreen to your children’ skin to reduce the risk of future skin damage, skin cancer, and related skin problems. Source: Federal Trade Commission http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2115
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Skin Cancer Summary: Skin cancer is the uncontrollable growth of abnormal cells in a layer of the skin. It attacks one out of every seven Americans each year, making it the most prevalent form of cancer. Source: American Society For Dermatologic Surgery http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6749
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Skin Cancer: Men Who Care About Their Skin Protect It Summary: Guidelines written especially for men about the benefits of sun protection during work and play outdoors. Following these tips will help in lowering their chance of getting skin cancer. Source: American Academy of Family Physicians http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6159
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The National Skin Cancer Prevention Education Program Summary: This NSCPEC is designed as a multidimensional national program based on research. Source: Division of Cancer Prevention and Control, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4699
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What You Need To Know About™ Skin Cancer Summary: This National Cancer Institute (NCI) booklet will give you some important information about skin cancer. Source: Cancer Information Service, National Cancer Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7129 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 skin 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
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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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WebMDHealth: http://my.webmd.com/health_topics
Associations and Skin Cancer The following is a list of associations that provide information on and resources relating to skin cancer: •
American Skin Association Telephone: (212) 753-8260 Toll-free: (800) 499-7546 Fax: (212) 688-6547 Email:
[email protected] Web Site: None Background: The American Skin Association (ASA) is a national nonprofit organization dedicated to building a network of lay people to achieve more effective prevention, treatment, and cure of skin disorders. ASA programs include generating support for skin research and providing information and education to the public regarding the skin and its disorders. ASA's mission is to identify, promote, and support research in biology of the skin, stimulate the transfer of advances in the field to clinical care of dermatology patients, and educate the community regarding diseases, symptoms, and care of the skin. To meet this goal, the Association engages in fundraising to support research and develops local chapters throughout the country. Information on a wide spectrum of skin disorders is available including 'Your Newborn s Skin and the Sun,' 'Ultraviolet Index: What You Need To Know,' 'Outdoor Sports and Your Skin,' and 'Proper Skin Care Can Make Gardening a Bed of Roses.' Founded in 1987, ASA also publishes 'SkinFacts,' a quarterly newsletter. Relevant area(s) of interest: Melanoma, Skin Cancer
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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, 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. Relevant area(s) of interest: Melanoma
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Hepatitis Foundation International Telephone: (301) 622-4200 Toll-free: (800) 891-0707 Fax: (301) 622-4702 Email:
[email protected] Web Site: http://www.hepatitisfoundation.org Background: Hepatitis Foundation International (HFI) is a voluntary not-for-profit membership organization dedicated to increasing awareness of the worldwide problem of viral hepatitis and educating the public and health care providers about its prevention, diagnosis, and treatment. Viral hepatitis is inflammatory liver disease caused by viral infection. There are several different forms of viral hepatitis that may be caused by different viruses. Such forms of hepatitis include hepatitis A, hepatitis B, hepatitis C, hepatitis D, and hepatitis E. Depending upon the specific form of the disease and other factors, viral hepatitis may cause liver cell damage, associated scarring of the liver (cirrhosis), and, in some cases, an increased risk of liver cancer. In some cases, affected individuals may have no apparent symptoms. In other cases, some adults with hepatitis A may have dark urine and light stools and may experience fatigue, nausea, vomiting, fever, abdominal pain, and/or abnormal yellowing of the skin and the whites of the eyes (jaundice). Some individuals with hepatitis B, C, D, or E may have dark urine and light stools and experience mild flu-like symptoms, fatigue, fever, and/or jaundice. Hepatitis Foundation International was established in 1995 and currently consists of approximately 35,000 members. The Foundation focuses exclusively on bringing viral hepatitis under control by supporting research to find cures; providing educational programs and materials to inform health professionals, affected individuals, family members, and the public concerning new diagnostic and treatment methods; and offering a support network for those who are affected by viral hepatitis. Hepatitis Foundation International also engages in patient advocacy and lobbying, provides appropriate referrals, and has a registry. The Foundation offers a wide range of educational materials including brochures, posters, information sheets, booklets, a primer for teachers concerning hepatitis B and substance abuse prevention, a coloring book for children, and a regular newsletter entitled 'Hepatitis Alert.'.
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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. Relevant area(s) of interest: Melanoma
•
March of Dimes Birth Defects Foundation Telephone: (914) 428-7100 Toll-free: (888) 663-4637 Fax: (914) 997-4763 Email:
[email protected] Web Site: http://www.marchofdimes.com Background: The March of Dimes Birth Defects Foundation is a national not-for-profit organization that was established in 1938. The mission of the Foundation is to improve the health of babies by preventing birth defects and infant mortality. The March of Dimes funds programs of research, community services, education, and advocacy. Educational programs that seek to prevent birth defects are important to the Foundation and to that end it also produces a wide variety of printed informational materials and videos. The Pregnancy and Newborn Health Education Center staffs trained health information specialists who provide researched information on pregnancy issues,
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complications and risks, newborn care, birth defects, genetic diseases and related topics as well as referrals to relevant organizations and support groups. •
Nevus Outreach, Inc Telephone: (918) 331-0595 Toll-free: (877) 426-3887 Fax: (918) 331-0595 Email:
[email protected] Web Site: http://www.nevus.org Background: Nevus Outreach, Inc. (NOI) is a nonprofit, 501 (c) (3) organization formed in 1997 by a group of parents dedicated to improving medical knowledge and treatment for individuals with giant congenital nevi and related disorders such as neurocutaneous melanosis. Giant congenital nevi are large, darkly pigmented moles or birthmarks (nevi) that are present at birth (congenital). Although such nevi may vary in size and shape and may cover any area of the body, they are often present on the chest, the shoulders, the upper back, the area covered by bathing trunks, the lower arms and legs, and/or various areas on the face and/or scalp. Individuals with giant nevi have an abnormally increased risk of developing malignant melanoma, a form of skin cancer. In addition, the nevus cells that appear on the skin may form in the central nervous system (neurocutaneous melanosis), which may cause neurological abnormalities and potentially life-threatening complications. The Nevus Outreach is committed to providing information, assistance, and support to affected individuals and family members; promoting additional research; and increasing awareness of these conditions among dermatologists and other health care professionals. NOI provides understandable information on these disorders; publishes a biannual newsletter entitled 'Nevus News'; provides periodic updates on important events and announcements; and sponsors a biannual conference to enable affected individuals and family members to network with one another and to interact with medical specialists in the field. The Nevus Outreach also acts as an advocate for affected families, helps make travel assistance arrangements for treatment, and provides referrals to other relevant organizations. In addition, the NOI has a Web site on the Internet that provides information on nevi disorders, online networking opportunities, and dynamic links to other helpful sources of information and support.
•
Rare Cancer Alliance Telephone: (520) 625-2132 Fax: (206) 600-6487 Email:
[email protected] Web Site: www.rare-cancer.org Background: The primary purpose of Rare Cancer Alliance is to disseminate information and provide support to rare cancer patients. On its website, it provides general cancer information, treatment options, and rare cancer differences. The website also provides a venue for raising awareness of rare cancers and funding for research. Most of the organization's members are rare cancer patients, and the alliance has a peer volunteer service through which members share their information gained through their own experiences with others.
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•
Skin Cancer Foundation Telephone: (212) 725-5176 Toll-free: (800) 754-6490 Fax: (212) 725-5751 Email:
[email protected] Background: The Skin Cancer Foundation is a not-for-profit international educational health organization dedicated to providing information on detection and prevention of and support to individuals with skin cancer. The Foundation seeks to educate the public about the different forms of skin cancer and promotes and supports ongoing medical research into the causes and treatment of these diseases. Established in 1977, the Skin Cancer Foundation has a growing membership of over 130 leading physicians. The Foundation provides support for medical research and training; functions as a major resource center for the media; and works to educate the public. Programs include screening clinics, health fairs, and corporate and community wellness programs. Educational materials produced by the organization include a wide variety of brochures, posters, books, newsletters, and audio-visual materials. Relevant area(s) of interest: Melanoma, Skin Cancer
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to skin cancer. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with skin 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 skin 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. 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 “skin cancer” (or a synonym), and you will receive information on all relevant organizations listed in the database.
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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 “skin 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 “skin 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 “skin 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
26
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/
•
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)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
•
California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
•
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/
•
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/
•
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/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
27
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries 475
•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
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
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
•
Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
•
Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
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/
•
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/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
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/
•
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
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
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 477
•
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
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
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/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
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
•
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
•
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/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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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
•
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/
•
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
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
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 skin cancer: •
Basic Guidelines for Skin Cancer Melanoma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000850.htm Melanoma of the eye Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001022.htm Skin cancer locations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002133.htm
•
Signs & Symptoms for Skin Cancer Blistering Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003939.htm Eyes, bulging Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003033.htm
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Itching Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003217.htm Painful eye Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003032.htm Poor vision Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003029.htm Skin lesion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Sunburn Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003227.htm •
Diagnostics and Tests for Skin Cancer Cranial CT scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003786.htm MRI of the head Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003791.htm Skin lesion biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003840.htm Ultrasound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003336.htm
•
Surgery and Procedures for Skin Cancer Skin graft Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002982.htm
•
Background Topics for Skin Cancer Benign Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002236.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm 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
Online Glossaries 481
Choroid Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002318.htm Conjunctiva Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002326.htm Iris Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002386.htm Macule Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003229.htm Melanin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002256.htm Metastasis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002260.htm Radiation therapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001918.htm Retina Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002291.htm Support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002150.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
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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SKIN CANCER DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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] Abrin: A toxic lectin from the seeds of jequirity, Abrus precatorius L. Very active poison. Five different proteins have so far been isolated: Abrus agglutinin, the component responsible for hemagglutininating activity, & abrins a-d, the toxic principles each consisting of two peptide chains are held together by disulfide bonds. [NIH] Absolute risk: The observed or calculated probability of an event in a population under study, as contrasted with the relative risk. [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] Accommodation: Adjustment, especially that of the eye for various distances. [EU] 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] Acid Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.2. [NIH] Acitretin: An oral retinoid effective in the treatment of psoriasis. It is the major metabolite of etretinate with the advantage of a much shorter half-life when compared with etretinate. [NIH]
Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics,
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adhesives and synthetic rubber. [NIH] Actinic keratosis: A precancerous condition of thick, scaly patches of skin. Also called solar or senile keratosis. [NIH] Actinomycosis: Infections with bacteria of the genus Actinomyces. [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] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [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] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [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]
Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH]
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Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Aetiology: Study of the causes of disease. [EU] 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] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Agarose: A polysaccharide complex, free of nitrogen and prepared from agar-agar which is produced by certain seaweeds (red algae). It dissolves in warm water to form a viscid solution. [NIH] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [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] Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Albinism: General term for a number of inherited defects of amino acid metabolism in which there is a deficiency or absence of pigment in the eyes, skin, or hair. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH]
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Alkaline: Having the reactions of an alkali. [EU] 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]
Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alloys: A mixture of metallic elements or compounds with other metallic or metalloid elements in varying proportions. [NIH] Alopecia: Absence of hair from areas where it is normally present. [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] Alum: A type of immune adjuvant (a substance used to help boost the immune response to a vaccine). Also called aluminum sulfate. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] 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 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] Aminolevulinic Acid: A compound produced from succinyl-CoA and glycine as an intermediate in heme synthesis. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] 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] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU]
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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] 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] 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] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] 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] 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] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [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] Antecedent: Existing or occurring before in time or order often with consequential effects. [EU]
Anterior chamber: The space in front of the iris and behind the cornea. [NIH] Anthralin: An anti-inflammatory anthracene derivative used for the treatment of dermatoses, especially psoriasis. It may cause folliculitis. [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]
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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] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsants: Drugs used to prevent seizures or reduce their severity. [NIH] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [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] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing 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] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] 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] Antipruritic: Relieving or preventing itching. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH]
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Apheresis: Components being separated out, as leukapheresis, plasmapheresis, plateletpheresis. [NIH] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] 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] 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] Argon: A noble gas with the atomic symbol Ar, atomic number 18, and atomic weight 39.948. It is used in fluorescent tubes and wherever an inert atmosphere is desired and nitrogen cannot be used. [NIH] Aromatic: Having a spicy odour. [EU] 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] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringent: Causing contraction, usually locally after topical application. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Asynchronous: Pacing mode where only one timing interval exists, that between the stimuli. While the duration of this interval may be varied, it is not modified by any sensed event once set. As no sensing occurs, the upper and lower rate intervals are the same as the pacema. [NIH]
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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] 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] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous tumor cells: Cancer cells from an individual's own tumor. [NIH] Autopsy: Postmortem examination of the body. [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 Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [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] Basal cell carcinoma: A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal Cell Nevus Syndrome: Hereditary disorder consisting of multiple basal cell carcinomas, odontogenic keratocysts, and multiple skeletal defects, e.g., frontal and temporoparietal bossing, bifurcated and splayed ribs, kyphoscoliosis, fusion of vertebrae, and cervicothoracic spina bifida. Genetic transmission is autosomal dominant. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [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
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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] 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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Beta carotene: A vitamin A precursor. Beta carotene belongs to the family of fat-soluble vitamins called carotenoids. [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 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] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] 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]
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Biotic: Pertaining to living organisms in their ecological rather than their physiological relations. [NIH] Bladder: The organ that stores urine. [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 Regions: Anatomical areas of the body. [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 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] Boron Neutron Capture Therapy: A technique for the treatment of neoplasms, especially gliomas and melanomas in which boron-10, an isotope, is introduced into the target cells followed by irradiation with thermal neutrons. [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] 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] Brain metastases: Cancer that has spread from the original (primary) tumor to the brain. [NIH]
Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breast Self-Examination: The inspection of one's breasts, usually for signs of disease, especially neoplastic disease. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU]
Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH]
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Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [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] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [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] 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] 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] Carmustine: An anticancer drug that belongs to the family of drugs called alkylating agents. [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]
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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] Castor Oil: Oil obtained from seeds of Ricinus communis that is used as a cathartic and as a plasticizer. [NIH] Cataracts: In medicine, an opacity of the crystalline lens of the eye obstructing partially or totally its transmission of light. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [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] Caustic: An escharotic or corrosive agent. Called also cauterant. [EU] 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 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 Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances. [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 proliferation: An increase in the number of cells as a result of cell growth and cell division. [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] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU]
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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 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] 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] Cesium: A member of the alkali metals. It has an atomic symbol Cs, atomic number 50, and atomic weight 132.91. Cesium has many industrial applications, including the construction of atomic clocks based on its atomic vibrational frequency. [NIH] Checkup: A general physical examination. [NIH] Cheilitis: Inflammation of the lips. It is of various etiologies and degrees of pathology. [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] 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] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Child Care: Care of children in the home or institution. [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] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Chlorofluorocarbons: A series of hydrocarbons containing both chlorine and fluorine. These have been used as refrigerants, blowing agents, cleaning fluids, solvents, and as fire extinguishing agents. They have been shown to cause stratospheric ozone depletion and have been banned for many uses. [NIH] Cholangiography: Radiographic examination of the bile ducts. [NIH] Cholesterol:
The principal sterol of all higher animals, distributed in body tissues,
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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] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chondrosarcoma: A type of cancer that forms in cartilage. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [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 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] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [NIH] Ciliary processes: The extensions or projections of the ciliary body that secrete aqueous humor. [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 study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [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] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
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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] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [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 physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH] Coal Tar: A by-product of the destructive distillation of coal used as a topical antieczematic. It is an antipruritic and keratoplastic agent used also in the treatment of psoriasis and other skin conditions. Occupational exposure to soots, tars, and certain mineral oils is known to be carcinogenic according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985) (Merck Index, 11th ed). [NIH] Cocarcinogenesis: The combination of two or more different factors in the production of cancer. [NIH] Coccidioidomycosis: An infectious disease caused by a fungus, Coccidioides immitis, that is prevalent in the western United States and is acquired by inhalation of dust containing the spores. [NIH] 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] 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]
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Collagenases: Enzymes that catalyze the degradation of collagen by acting on the peptide bonds. EC 3.4.24.-. [NIH] 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] Colorectal: Having to do with the colon or the rectum. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Communis: Common tendon of the rectus group of muscles that surrounds the optic foramen and a portion of the superior orbital fissure, to the anterior margin of which it is attached at the spina recti lateralis. [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] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [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]
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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] Compound nevus: A type of mole formed by groups of nevus cells found in the epidermis and dermis (the two main layers of tissue that make up the skin). [NIH] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [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 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 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] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [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] 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] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]
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
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studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH] Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Cooperative group: A group of physicians, hospitals, or both formed to treat a large number of persons in the same way so that new treatment can be evaluated quickly. Clinical trials of new cancer treatments often require many more people than a single physician or hospital can care for. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] 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 Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [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] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] 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] Croton Oil: Viscous, nauseating oil obtained from the shrub Croton tiglium (Euphorbaceae). It is a vesicant and skin irritant used as pharmacologic standard for skin inflammation and allergy and causes skin cancer. It was formerly used as an emetic and cathartic with frequent mortality. [NIH]
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Cryosurgery: The use of freezing as a special surgical technique to destroy or excise tissue. [NIH]
Cryotherapy: Any method that uses cold temperature to treat disease. [NIH] Cultured cell line: Cells of a single type that have been grown in the laboratory for several generations (cell divisions). [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curettage: Removal of tissue with a curette, a spoon-shaped instrument with a sharp edge. [NIH]
Curette: A spoon-shaped instrument with a sharp edge. [NIH] Cutaneous: Having to do with the skin. [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] Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with cyclins to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. [NIH]
Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [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] Cytotoxic: Cell-killing. [NIH] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dacarbazine: An anticancer drug that belongs to the family of drugs called alkylating agents. [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]
De novo: In cancer, the first occurrence of cancer in the body. [NIH]
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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] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [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] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Denileukin diftitox: A substance used to treat cutaneous T-cell lymphoma when other treatments have not worked. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Depigmentation: Removal or loss of pigment, especially melanin. [EU] 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] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatologist: A doctor who specializes in the diagnosis and treatment of skin problems. [NIH]
Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Desiccation: Removal of moisture from a substance (chemical, food, tissue, etc.). [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Developed Countries:
Countries that have reached a level of economic achievement
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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 esterified form in treatment of conditions that respond generally to cortisone. [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] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diathesis: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the person more than usually susceptible to certain diseases. [EU] Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt, diclofenac sodium. [NIH] Diclofenac Sodium: The sodium form of diclofenac. It is used for its analgesic and antiinflammatory properties. [NIH] Diethylstilbestrol: DES. 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] 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] 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] Discoid: Shaped like a disk. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense
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mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Diuresis: Increased excretion of urine. [EU] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] 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] 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 Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [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] 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] Dysplastic nevi: Atypical moles; moles whose appearance is different from that of common moles. Dysplastic nevi are generally larger than ordinary moles and have irregular and indistinct borders. Their color frequently is not uniform and ranges from pink to dark brown; they usually are flat, but parts may be raised above the skin surface. [NIH] Dysplastic nevus: An atypical mole; a mole whose appearance is different from that of a common mole. A dysplastic nevus is generally larger than an ordinary mole and has irregular and indistinct borders. Its color frequently is not uniform and ranges from pink to
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dark brown; it is usually flat, but parts may be raised above the skin surface. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Ectoderm: The outer of the three germ layers of the embryo. [NIH] Ectodermal Dysplasia: A group of hereditary disorders involving tissues and structures derived from the embryonic ectoderm. They are characterized by the presence of abnormalities at birth and involvement of both the epidermis and skin appendages. They are generally nonprogressive and diffuse. Various forms exist, including anhidrotic and hidrotic dysplasias, focal dermal hypoplasia, and aplasia cutis congenita. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] 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] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elasticity: Resistance and recovery from distortion of shape. [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] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrodesiccation: The drying of tissue by a high-frequency electric current applied with a needle-shaped electrode. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [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] Emetic: An agent that causes vomiting. [EU] Emollient: Softening or soothing; called also malactic. [EU] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of
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tissue. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endostatin: A drug that is being studied for its ability to prevent the growth of new blood vessels into a solid tumor. Endostatin belongs to the family of drugs called angiogenesis inhibitors. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [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] 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] 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]
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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] Epidermodysplasia Verruciformis: An autosomal recessive trait with impaired cellmediated immunity. About 15 human papillomaviruses are implicated in associated infection, four of which lead to skin neoplasms. The disease begins in childhood with red papules and later spreads over the body as gray or yellow scales. [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [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] Episode of Care: An interval of care by a health care facility or provider for a specific medical problem or condition. It may be continuous or it may consist of a series of intervals marked by one or more brief separations from care, and can also identify the sequence of care (e.g., emergency, inpatient, outpatient), thus serving as one measure of health care provided. [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] Epithelioma: A neoplasm of epithelial origin, ranging from benign (adenoma and papilloma) to malignant (carcinoma). [EU] 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]
Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [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] Estrogen: One of the two female sex hormones. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Etretinate: An oral retinoid used in the treatment of keratotic genodermatosis, lichen planus, and psoriasis. Beneficial effects have also been claimed in the prophylaxis of epithelial neoplasia. The compound may be teratogenic. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a
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suitable consistency or form to the drug; a vehicle. [EU] Excisional: The surgical procedure of removing a tumor by cutting it out. The biopsy is then examined under a microscope. [NIH] Excisional biopsy: A surgical procedure in which an entire lump or suspicious area is removed for diagnosis. The tissue is then examined under a microscope. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [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] Extraction: The process or act of pulling or drawing out. [EU] Extraocular: External to or outside of the eye. [NIH] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Eye Color: Color of the iris. [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] Eye socket: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Family Practice: A medical specialty concerned with the provision of continuing, comprehensive primary health care for the entire family. [NIH] Fat: Total lipids including phospholipids. [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
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development. [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] 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] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fine-needle aspiration: The removal of tissue or fluid with a needle for examination under a microscope. Also called needle biopsy. [NIH] Flavopiridol: Belongs to the family of anticancer drugs called flavinols. [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] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [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] Fold: A plication or doubling of various parts of the body. [NIH] Follicles: Shafts through which hair grows. [NIH] Folliculitis: Inflammation of follicles, primarily hair follicles. [NIH] Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. [NIH]
Forearm: The part between the elbow and the wrist. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [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,
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damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [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] Fungistatic: Inhibiting the growth of fungi. [EU] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gallate: Antioxidant present in tea. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [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] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] 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] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [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 Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of
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homologous recombination. [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] 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 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] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [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] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] 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] 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]
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]
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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] 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] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [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] Hair Color: Color of hair or fur. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH]
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Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] 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 Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Fairs: Community health education events focused on prevention of disease and promotion of health through audiovisual exhibits. [NIH] Health Policy: Decisions, usually developed by government policymakers, for determining present and future objectives pertaining to the health care system. [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Health Resources: Available manpower, facilities, revenue, equipment, and supplies to produce requisite health care and services. [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 Transplantation: The transference of a heart from one human or animal to another. [NIH]
Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodiafiltration: The combination of hemodialysis and hemofiltration either simultaneously or sequentially. Convective transport (hemofiltration) may be better for removal of larger molecular weight substances and diffusive transport (hemodialysis) for smaller molecular weight solutes. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemofiltration: Extracorporeal ultrafiltration technique without hemodialysis for treatment of fluid overload and electrolyte disturbances affecting renal, cardiac, or pulmonary function. [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]
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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] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] HER2/neu: Human epidermal growth factor receptor 2. The HER2-neu protein is involved in growth of some cancer cells. Also called c-erbB-2. [NIH] Herbicide: A chemical that kills plants. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] 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] 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] 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] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] 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] Hormonal: Pertaining to or of the nature of a hormone. [EU] 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] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is
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often associated with some types of cancer. [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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [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] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [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] Hypnotic: A drug that acts to induce sleep. [EU] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [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] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune adjuvant: A drug that stimulates the immune system to respond to disease. [NIH] 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
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Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. [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] Immunogen: A substance that is capable of causing antibody formation. [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] Immunotoxins: Semisynthetic conjugates of various toxic molecules, including radioactive isotopes and bacterial or plant toxins, with specific immune substances such as immunoglobulins, monoclonal antibodies, and antigens. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect. [NIH] 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]
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In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] 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] Incisional: The removal of a sample of tissue for examination under a microscope. [NIH] Incisional biopsy: A surgical procedure in which a portion of a lump or suspicious area is removed for diagnosis. The tissue is then examined under a microscope. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU]
Indolent: A type of cancer that grows slowly. [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 Mortality: Perinatal, neonatal, and infant deaths in a given population. [NIH] 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] 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] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] 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] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role
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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] 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-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] 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-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [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] 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] Intestinal: Having to do with the intestines. [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] Intracellular: Inside a cell. [NIH] Intraocular: Within the eye. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] 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]
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] Involuntary: Reaction occurring without intention or volition. [NIH]
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Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Iodine-131: Radioactive isotope of iodine. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] 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] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiance: At a point of a surface, the quotient of the radiant flux incident on an element of the surface containing the point, by the area of that element. [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] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isolated hepatic perfusion: A procedure in which a catheter is placed into the artery that provides blood to the liver; another catheter is placed into the vein that takes blood away from the liver. This temporarily separates the liver's blood supply from blood circulating throughout the rest of the body and allows high doses of anticancer drugs to be directed to the liver only. [NIH] Isolated limb perfusion: A technique that may be used to deliver anticancer drugs directly to an arm or leg. The flow of blood to and from the limb is temporarily stopped with a tourniquet, and anticancer drugs are put directly into the blood of the limb. This allows the person to receive a high dose of drugs in the area where the cancer occurred. [NIH] Isothiocyanates: Organic compounds with the general formula R-NCS. [NIH] Isotretinoin: A topical dermatologic agent that is used in the treatment of acne vulgaris and several other skin diseases. The drug has teratogenic and other adverse effects. [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]
Junctional nevus: A mole found in the junction (border) between the epidermis and dermis layers of the skin. These moles may be pigmented and slightly raised, and have a higher risk of developing into malignant melanoma. [NIH]
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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] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratoacanthoma: A benign, non-neoplastic, usually self-limiting epithelial lesion closely resembling squamous cell carcinoma clinically and histopathologically. It occurs in solitary, multiple, and eruptive forms. The solitary and multiple forms occur on sunlight exposed areas and are identical histologically; they affect primarily white males. The eruptive form usually involves both sexes and appears as a generalized papular eruption. [NIH] Keratosis: Any horny growth such as a wart or callus. [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] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lactate Dehydrogenase: A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of lactate and pyruvate. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist. [NIH] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] 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 membrane. Evidence suggests that the protein plays a role in tumor invasion. [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] Laser Surgery: The use of a laser either to vaporize surface lesions or to make bloodless cuts in tissue. It does not include the coagulation of tissue by laser. [NIH] Laser therapy: The use of an intensely powerful beam of light to kill cancer cells. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Latent period: A seemingly inactive period, as that between exposure of tissue to an injurious agent and the manifestation of response, or that between the instant of stimulation and the beginning of response. [EU]
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Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
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] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lentigo: Small circumscribed melanoses resembling, but differing histologically from, freckles. The concept includes senile lentigo ('liver spots') and nevoid lentigo (nevus spilus, lentigo simplex) and may also occur in association with multiple congenital defects or congenital syndromes (e.g., Peutz-Jeghers syndrome). [NIH] Lethal: Deadly, fatal. [EU] Leukapheresis: The preparation of leukocyte concentrates with the return of red cells and leukocyte-poor plasma to the donor. [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] Leukoplakia: A white patch that may develop on mucous membranes such as the cheek, gums, or tongue and may become cancerous. [NIH] Library Services: circulation. [NIH]
Services offered to the library user. They include reference and
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] Limb perfusion: A technique that may be used to deliver anticancer drugs directly to an arm or leg. The flow of blood to and from the limb is temporarily stopped with a tourniquet, and anticancer drugs are put directly into the blood of the limb. This allows the person to receive a high dose of drugs in the area where the cancer occurred. [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] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [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] Litter: Appliance consisting of an oblong frame over which is stretched a canvas or other material, used for carrying an injured or disabled person. [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 cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH] Liver metastases: Cancer that has spread from the original (primary) tumor to the liver. [NIH]
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Liver Neoplasms: Tumors or cancer of 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] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Local Government: Smallest political subdivisions within a country at which general governmental functions are carried-out. [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] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [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] Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair. It is detected when heterozygous markers for a locus appear monomorphic because one of the alleles was deleted. When this occurs at a tumor suppressor gene locus where one of the alleles is already abnormal, it can result in neoplastic transformation. [NIH] Lubricants: Oily or slippery substances. [NIH] 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]
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 Metastasis: Transfer of a neoplasm from its primary site to lymph nodes or to distant parts of the body by way of the lymphatic system. [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] 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] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH]
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Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphoscintigraphy: A method used to identify the sentinel node (the first draining lymph node near a tumor). A radioactive substance that can be taken up by lymph nodes is injected at the site of the tumor, and a doctor follows the movement of this substance on a computer screen. Once the lymph nodes that have taken up the substance are identified, they can be removed and examined to see if they contain tumor cells. [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] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [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]
Mammary: Pertaining to the mamma, or breast. [EU] Marital Status: A demographic parameter indicating a person's status with respect to marriage, divorce, widowhood, singleness, etc. [NIH] Mass Screening: Organized periodic procedures performed on large groups of people for the purpose of detecting disease. [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] 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:
Recording of pertinent information concerning patient's illness or
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illnesses. [NIH] Medically Underserved Area: A geographic location which has insufficient health resources (manpower and/or facilities) to meet the medical needs of the resident population. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] 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] Melanoma vaccine: A cancer vaccine prepared from human melanoma cancer cells. It can be used alone or with other therapy in treating melanoma. [NIH] Melanosis: Disorders of increased melanin pigmentation that develop without preceding inflammatory disease. [NIH] Melanosomes: Melanin-containing organelles found in melanocytes and melanophores. [NIH]
Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [NIH] Membrane: A very thin layer of tissue that covers a surface. [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] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningioma: A type of tumor that occurs in the meninges, the membranes that cover and protect the brain and spinal cord. Meningiomas usually grow slowly. [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] 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] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed
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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] Methoxsalen: A naturally occurring furocoumarin compound found in several species of plants, including Psoralea corylifolia. It is a photoactive substance that forms DNA adducts in the presence of ultraviolet A irradiation. [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] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [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] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [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] 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] Mineral Oil: A mixture of liquid hydrocarbons obtained from petroleum. It is used as laxative, lubricant, ointment base, and emollient. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei
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normally receive identical complements of the number of chromosomes of the somatic cells of the species. [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] 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] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morale: The prevailing temper or spirit of an individual or group in relation to the tasks or functions which are expected. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]
Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motivations: The most compelling inner determinants of human behavior; also called drives, urges, impulses, needs, wants, tensions, and willful cravings. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multiphasic Screening: The simultaneous use of multiple laboratory procedures for the detection of various diseases. These are usually performed on groups of people. [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]
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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] Myelodysplastic syndrome: Disease in which the bone marrow does not function normally. Also called preleukemia or smoldering leukemia. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myeloproliferative Disorders: Disorders in which one or more stimuli cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. [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] Myristate: Pharmacological activator of protein kinase C. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [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] Needle biopsy: The removal of tissue or fluid with a needle for examination under a microscope. Also called fine-needle aspiration. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] 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]
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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] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [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] Neural Crest: A strip of specialized ectoderm flanking each side of the embryonal neural plate, which after the closure of the neural tube, forms a column of isolated cells along the dorsal aspect of the neural tube. Most of the cranial and all of the spinal sensory ganglion cells arise by differentiation of neural crest cells. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU]
Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] 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] Neutron Capture Therapy: A technique for the treatment of neoplasms in which an isotope is introduced into target cells followed by irradiation with thermal neutrons. [NIH] 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] Nevus: A benign growth on the skin, such as a mole. A mole is a cluster of melanocytes and surrounding supportive tissue that usually appears as a tan, brown, or flesh-colored spot on the skin. The plural of nevus is nevi (NEE-vye). [NIH] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [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] Nitrosamines: A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties. [NIH] Nonmelanoma skin cancer: Skin cancer that arises in basal cells or squamous cells but not in melanocytes (pigment-producing cells of the skin). [NIH] Non-small cell lung cancer:
A group of lung cancers that includes squamous cell
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carcinoma, adenocarcinoma, and large cell carcinoma. [NIH] Notochord: The rod-shaped body, composed of cells derived from the mesoblast and defining the primitive axis of the embryo. In lower vertebrates, it persists throughout life as the main axial support of the body, but in higher vertebrates it is replaced by the vertebral column. [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 Medicine: A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds in a pharmaceutical form. [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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nurse Practitioners: Nurses who are specially trained to assume an expanded role in providing medical care under the supervision of a physician. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation. [NIH] Occupational Health: The promotion and maintenance of physical and mental health in the work environment. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] 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] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [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] 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] Oncolysis: The destruction of or disposal by absorption of any neoplastic cells. [NIH] Oncolytic: Pertaining to, characterized by, or causing oncolysis (= the lysis or destruction of tumour cells). [EU] Opacity: Degree of density (area most dense taken for reading). [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Organogenesis: Clonal propagation which involves culturing explants from roots, leaves, or stems to form undifferentiated callus tissue; after the cells form shoots, they are separated and rooted. Alternatively, if the callus is put in liquid culture, somatic embryos form. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Osteomyelitis: Inflammation of bone caused by a pyogenic organism. It may remain localized or may spread through the bone to involve the marrow, cortex, cancellous tissue, and periosteum. [EU] 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 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] 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]
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] Palladium: A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU]
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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] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Papule: A small circumscribed, superficial, solid elevation of the skin. [EU] 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] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] 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] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [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] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathologist: A doctor who identifies diseases by studying cells and tissues under a microscope. [NIH] Patient Advocacy: Promotion and protection of the rights of patients, frequently through a legal process. [NIH] 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
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information about PDQ can be found at http://cancernet.nci.nih.gov/pdq.html. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [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] Perennial: Lasting through the year of for several years. [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] Perianal: Located around the anus. [EU] Periorbital: Situated around the orbit, or eye socket. [EU] 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 Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy. [NIH] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU]
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] 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] Phenyl: Ingredient used in cold and flu remedies. [NIH]
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Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [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] Photoallergy: Sensitization of the skin to light usually due to the action of certain substances or drugs, may occur shortly after exposure to a substance or after a latent period of from days to months. [NIH] Photobiology: The branch of biology dealing with the effect of light on organisms. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photophobia: Abnormal sensitivity to light. This may occur as a manifestation of eye diseases; migraine; subarachnoid hemorrhage; meningitis; and other disorders. Photophobia may also occur in association with depression and other mental disorders. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Photosensitivity Disorders: Abnormal responses to sunlight or artificial light due to extreme reactivity of light-absorbing molecules in tissues. It refers almost exclusively to skin photosensitivity, including sunburn, reactions due to repeated prolonged exposure in the absence of photosensitizing factors, and reactions requiring photosensitizing factors such as photosensitizing agents and certain diseases. With restricted reference to skin tissue, it does not include photosensitivity of the eye to light, as in photophobia or photosensitive epilepsy. [NIH]
Photosensitizing Agents: Drugs that are pharmacologically inactive but when exposed to ultraviolet radiation or sunlight are converted to their active metabolite to produce a beneficial reaction affecting the diseased tissue. These compounds can be administered topically or systemically and have been used therapeutically to treat psoriasis and various types of neoplasms. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [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.
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[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] Phytotoxin: A substance which is toxic for plants. [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] Pitch: The subjective awareness of the frequency or spectral distribution of a sound. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [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] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [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] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [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] Plateletpheresis: The preparation of platelet concentrates with the return of red cells and
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platelet-poor plasma to the donor. [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]
Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polycyclic Hydrocarbons: Hydrocarbons consisting of two or more fused ring structures. [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] 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] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyvalent: Having more than one valence. [EU] 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] Postnatal: Occurring after birth, with reference to the newborn. [EU] 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] Potassium hydroxide: A toxic and highly corrosive chemical used to make soap, in bleaching, and as a paint remover. It is used in small amounts as a food additive and in the preparatrion of some drugs. [NIH]
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Potentiates: 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] Power Plants: Units that convert some form of energy into electrical energy, such as hydroelectric or steam-generating stations, diesel-electric engines in locomotives, or nuclear power plants. [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] 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] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] 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] Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] 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] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [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 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] Private Sector: That distinct portion of the institutional, industrial, or economic structure of a country that is controlled or owned by non-governmental, private interests. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of
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strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Professional Practice: The use of one's knowledge in a particular profession. It includes, in the case of the field of biomedicine, professional activities related to health care and the actual performance of the duties related to the provision of health care. [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 Development: The process of formulating, improving, and expanding educational, managerial, or service-oriented work plans (excluding computer program development). [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] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Proneness: Susceptibility to accidents due to human factors. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] 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 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)-15-
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hydroxy-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] 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] Prostatic acid phosphatase: PAP. An enzyme produced by the prostate. It may be found in increased amounts in men who have prostate cancer. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protective Clothing: Clothing designed to protect the individual against possible exposure to known hazards. [NIH] 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] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [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] 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]
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Proxy: A person authorized to decide or act for another person, for example, a person having durable power of attorney. [NIH] Pruritic: Pertaining to or characterized by pruritus. [EU] Psoralen: A substance that binds to the DNA in cells and stops them from multiplying. It is being studied in the treatment of graft-versus-host disease and is used in the treatment of psoriasis and vitiligo. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] PTC: Percutaneous transhepatic cholangiography (per-kyoo-TAN-ee-us trans-heh-PAT-ik ko-LAN-jee-AH-gra-fee). A procedure to x-ray the bile ducts. In this procedure, a dye is injected through a thin needle inserted through the skin into the liver or the gallbladder, and an x-ray picture is taken. [NIH] 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] 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]
Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] 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] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyrazoloacridine: An anticancer drug that belongs to the family of drugs called acridines. [NIH]
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] Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [NIH]
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Quiescent: Marked by a state of inactivity or repose. [EU] 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] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [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] Radiation, Ionizing: Electromagnetic or corpuscular radiation capable of producing ions, directly or indirectly, in its passage through matter. The wavelengths are equal to or smaller than those of short (far) ultraviolet radiation and include gamma and X-rays and highenergy elementary particles. [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] Radiodermatitis: A cutaneous inflammatory reaction occurring as a result of exposure to ionizing radiation. [NIH] 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] Radiolabeled: Any compound that has been joined with a radioactive substance. [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] 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] Radium: A radioactive element of the alkaline earth series of metals. It has the atomic symbol Ra, atomic number 88, and atomic weight 226. Radium is the product of the disintegration of uranium and is present in pitchblende and all ores containing uranium. It is used clinically as a source of beta and gamma-rays in radiotherapy, particularly brachytherapy. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and
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control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [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 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] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] 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] 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 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]
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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 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] 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] Repopulation: The replacement of functional cells, usually by proliferation, following or during irradiation. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [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
Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] 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] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoblastoma Protein: Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with
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the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein. [NIH]
Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhinophyma: A manifestation of severe Acne rosacea resulting in significant enlargement of the nose and occurring primarily in men. It is caused by hypertrophy of the sebaceous glands and surrounding connective tissue. The nose is reddened and marked with numerous telangiectasias. [NIH] Rhizoxin: An anticancer drug isolated from a fungus. It is similar to the family of drugs called vinca alkaloids. [NIH] Ricin: A protein phytotoxin from the seeds of Ricinus communis, the castor oil plant. It agglutinates cells, is proteolytic, and causes lethal inflammation and hemorrhage if taken internally. [NIH] 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] Role Playing: The adopting or performing the role of another significant individual in order to gain insight into the behavior of that person. [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] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Saccharin: Flavoring agent and non-nutritive sweetener. [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] Sargramostim: A colony-stimulating factor that stimulates the production of blood cells, especially platelets, during chemotherapy. It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called GM-CSF. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main
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body of the chromosome. [NIH] Scabies: A contagious cutaneous inflammation caused by the bite of the mite Sarcoptes scabiei. It is characterized by pruritic papular eruptions and burrows and affects primarily the axillae, elbows, wrists, and genitalia, although it can spread to cover the entire body. [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] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] School Health Services: Preventive health services provided for students. It excludes college or university students. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] 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] Scrotum: In males, the external sac that contains the testicles. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [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] Secular trends: A relatively long-term trend in a community or country. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedatives, Barbiturate: Those derivatives of barbituric or thiobarbituric acid that are used as hypnotics or sedatives. The structural class of all such derivatives, regardless of use, is barbiturates. [NIH] 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
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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] Self-Examination: The inspection of one's own body, usually for signs of disease (e.g., breast self-examination, testicular self-examination). [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sentinel Lymph Node Biopsy: A diagnostic procedure used to determine whether lymphatic metastasis has occurred. The sentinel lymph node is the first lymph node to receive drainage from a neoplasm. [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] Serrata: The serrated anterior border of the retina located approximately 8.5 mm from the limbus and adjacent to the pars plana of the ciliary body. [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
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] 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 receptor-
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mediated 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] Skeletal: Having to do with the skeleton (boney part of the body). [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] Skin Abnormalities: Congenital structural abnormalities of the skin. [NIH] Skin Aging: The process of aging due to changes in the structure and elasticity of the skin over time. It may be a part of physiological aging or it may be due to the effects of ultraviolet radiation, usually through exposure to sunlight. [NIH] Skin graft: Skin that is moved from one part of the body to another. [NIH] Skin Neoplasms: Tumors or cancer of the skin. [NIH] Skin Pigmentation: Coloration of the skin. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [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]
Social Class: A stratum of people with similar position and prestige; includes social stratification. Social class is measured by criteria such as education, occupation, and income. [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] 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, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Soft tissue sarcoma: A sarcoma that begins in the muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH]
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Solar radiation: Sunbathing as a therapeutic measure. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] 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] Somatotropin: A small peptide hormone released by the anterior pituitary under hypothalamic control. Somatotropin, or growth hormone, stimulates mitosis, cell growth, and, for some cell types, differentiation in many tissues of the body. It has profound effects on many aspects of gene expression and metabolism. [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] 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] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [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] Spinous: Like a spine or thorn in shape; having spines. [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] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Squamous: Scaly, or platelike. [EU]
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Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Staff Development: The process by which the employer promotes staff performance and efficiency consistent with management goals and objectives. [NIH] 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] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [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] 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] 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] 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]
Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH]
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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] Subcutaneous: Beneath the skin. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [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] Subungual: Beneath a nail. [NIH] 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] Sun protection factor: SPF. A scale for rating the level of sunburn protection in sunscreen products. The higher the SPF, the more sunburn protection it provides. Sunscreens with an SPF value of 2 through 11 provide minimal protection against sunburns. Sunscreens with an SPF of 12 through 29 provide moderate protection, which is adequate for most people. Those with an SPF of 30 or higher provide high protection against sunburn and are sometimes recommended for people who are highly sensitive to the sun. [NIH] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [NIH] Sunscreening Agents: Chemical or physical agents that protect the skin from sunburn and erythema by absorbing or blocking ultraviolet radiation. [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] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] 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]
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Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] 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] Systemic: Affecting the entire body. [NIH] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Tax Exemption: Status not subject to taxation; as the income of a philanthropic organization. Tax-exempt organizations may also qualify to receive tax-deductible donations if they are considered to be nonprofit corporations under Section 501(c)3 of the United States Internal Revenue Code. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Temozolomide: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [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
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reintroduced and used for a number of immunological and inflammatory disorders. 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] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thiouracil: Occurs in seeds of Brassica and Crucifera species. Thiouracil has been used as antithyroid, coronary vasodilator, and in congestive heart failure although its use has been largely supplanted by other drugs. It is known to cause blood dyscrasias and suspected of terato- and carcinogenesis. [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] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [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] 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, 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 Expansion: Process whereby tissue adjacent to a soft tissue defect is expanded by means of a subcutaneously implanted reservoir. The procedure is used in reconstructive surgery for injuries caused by trauma, burns, or ablative surgery. [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
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undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Topical chemotherapy: Treatment with anticancer drugs in a lotion or cream applied to the skin. [NIH] Tourniquet: A device, band or elastic tube applied temporarily to press upon an artery to stop bleeding; a device to compress a blood vessel in order to stop bleeding. [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] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [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 (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [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] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH]
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Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, 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] Triad: Trivalent. [NIH] Triage: The sorting out and classification of patients or casualties to determine priority of need and proper place of treatment. [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] 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 model: A type of animal model which can be 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] 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] Tumor-derived: Taken from an individual's own tumor tissue; may be used in the development of a vaccine that enhances the body's ability to build an immune response to the tumor. [NIH] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [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] Tyrosinase peptide: A tumor-specific antigen used in the development of cancer vaccines. [NIH]
Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is
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also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ultrafiltration: The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in dialysis separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as hemofiltration or hemodiafiltration (if combined with hemodialysis). [NIH] Ultraviolet radiation: Invisible rays that are part of the energy that comes from the sun. UV radiation can damage the skin and cause melanoma and other types of skin cancer. UV radiation that reaches the earth's surface is made up of two types of rays, called UVA and UVB rays. UVB rays are more likely than UVA rays to cause sunburn, but UVA rays pass deeper into the skin. Scientists have long thought that UVB radiation can cause melanoma and other types of skin cancer. They now think that UVA radiation also may add to skin damage that can lead to skin cancer and cause premature aging. For this reason, skin specialists recommend that people use sunscreens that reflect, absorb, or scatter both kinds of UV radiation. [NIH] Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants. [NIH]
Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Urban Population: The inhabitants of a city or town, including metropolitan areas and suburban areas. [NIH] Urease: An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. EC 3.5.1.5. [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] 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] Vaginal: Of or having to do with the vagina, the birth canal. [NIH]
Dictionary 555
Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [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] Venter: Belly. [NIH] 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] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verruca: A circumscribed, cutaneous excrescence having a papilliferous surface; a small, circumscribed, epidermal tumor. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] 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] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Vinyl Chloride: A gas that has been used as an aerosol propellant and is the starting material for polyvinyl resins. Toxicity studies have shown various adverse effects, particularly the occurrence of liver neoplasms. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [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,
556 Skin Cancer
especially in the abdomen. [NIH] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] 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] Vulva: The external female genital organs, including the clitoris, vaginal lips, and the opening to the vagina. [NIH] Vulvar Neoplasms: Tumors or cancer of the vulva. [NIH] War: Hostile conflict between organized groups of people. [NIH] Wart: A raised growth on the surface of the skin or other organ. [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] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Xeroderma Pigmentosum: A rare, pigmentary, and atrophic autosomal recessive disease affecting all races. It is manifested as an extreme photosensitivity to ultraviolet light as the result of a deficiency in the enzyme that permits excisional repair of ultraviolet-damaged DNA. [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] Zinc Oxide: A mild astringent and topical protectant with some antiseptic action. It is also used in bandages, pastes, ointments, dental cements, and as a sunblock. [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]
557
INDEX A Abdomen, 273, 278, 483, 492, 495, 507, 512, 518, 520, 521, 531, 532, 547, 548, 551, 556 Abdominal, 467, 483, 504, 510, 531, 532 Abdominal Pain, 467, 483, 510 Abrin, 311, 483 Absolute risk, 18, 483 Acceptor, 483, 530, 552 Accommodation, 395, 483 Acetaminophen, 288, 483 Acetylcholine, 483, 496, 528 Acid Phosphatase, 483 Acitretin, 483 Acne, 483, 519, 543 Acne Vulgaris, 483, 519 Acquired Immunodeficiency Syndrome, 382, 483 Acrylonitrile, 483, 543 Actinic keratosis, 4, 29, 343, 451, 453, 454, 484 Actinomycosis, 484 Acute myelogenous leukemia, 484 Acute myeloid leukemia, 280, 484 Acute nonlymphocytic leukemia, 484 Adaptability, 484, 494 Adaptation, 10, 484 Adenocarcinoma, 484, 529 Adenoma, 484, 507 Adenosine, 484, 493, 533 Adenovirus, 369, 484, 543 Adjunctive Therapy, 376, 484 Adjustment, 6, 36, 259, 262, 404, 483, 484 Adjuvant, 25, 38, 278, 280, 341, 345, 361, 376, 463, 484 Adjuvant Therapy, 25, 38, 278, 361, 376, 463, 484 Adolescence, 19, 29, 37, 38, 458, 484, 532 Adoptive Transfer, 315, 316, 317, 318, 336, 484 Adrenal Medulla, 485, 507 Adrenergic, 485, 507, 550 Adverse Effect, 485, 519, 545, 555 Aerosol, 485, 555 Aetiology, 379, 381, 485 Affinity, 311, 485, 489, 546 Agar, 485, 534 Agarose, 326, 485 Age Groups, 12, 27, 29, 485
Age-Adjusted, 18, 392, 407, 457, 485 Aged, 80 and Over, 485 Ageing, 372, 485 Agonist, 485, 550 Albinism, 485 Alertness, 485, 493 Algorithms, 23, 485, 491 Alkaline, 486, 493, 540 Alkylating Agents, 486, 493, 501, 550 Alleles, 308, 318, 486, 522 Allogeneic, 319, 321, 337, 339, 353, 486, 512, 532 Allograft, 486 Alloys, 486, 530 Alopecia, 486, 501 Alpha Particles, 486, 540 Alternative medicine, 420, 486 Alum, 285, 486 Aluminum, 486 Amino Acid Sequence, 314, 486, 488, 511 Aminolevulinic Acid, 4, 126, 257, 262, 486 Amplification, 304, 309, 352, 486 Anaesthesia, 486, 517 Anal, 252, 486, 506 Analgesic, 483, 486, 503 Analog, 487, 509 Analogous, 487, 504, 535, 552 Anaphylatoxins, 487, 498 Anatomical, 29, 380, 487, 492, 495, 516, 544 Anemia, 442, 487 Anesthesia, 273, 278, 411, 487 Anesthetics, 487, 490, 507 Angiogenesis, 261, 351, 487, 506, 523 Angiogenesis inhibitor, 487, 506 Animal model, 17, 302, 324, 327, 337, 339, 342, 369, 371, 487, 553 Annealing, 487, 535 Anorexia, 487, 510 Antagonism, 487, 493 Antecedent, 386, 487 Anterior chamber, 487, 519 Anthralin, 390, 487 Antibacterial, 327, 487, 547 Antibiotic, 487, 492, 501, 504, 547 Antibody therapy, 280, 282, 488 Anticoagulant, 488, 538 Anticonvulsants, 488 Antifungal, 327, 488
558 Skin Cancer
Antigen, 28, 300, 301, 302, 303, 311, 314, 315, 316, 317, 318, 319, 321, 322, 328, 331, 332, 333, 335, 336, 337, 338, 340, 341, 345, 350, 353, 356, 358, 366, 485, 488, 498, 502, 514, 515, 516, 517, 523, 543, 553 Antigen-Antibody Complex, 488, 498 Antigen-presenting cell, 488, 502 Anti-infective, 488, 519 Anti-inflammatory, 343, 483, 487, 488, 500, 503, 511, 531 Antimetabolite, 488, 509, 525 Antineoplastic, 327, 486, 488, 500, 501, 504, 509, 524, 525, 530, 555 Antioxidant, 253, 260, 262, 263, 488, 510, 546 Antipruritic, 488, 497 Antipyretic, 483, 488, 503 Antiseptic, 488, 556 Antithrombotic, 327, 488 Antiviral, 488, 516, 518 Anus, 486, 488, 492, 498, 532, 541 Apheresis, 292, 489 Aplasia, 489, 505 Apoptosis, 335, 348, 489 Aqueous, 489, 491, 496, 501, 521 Arachidonic Acid, 489, 537 Arginine, 427, 487, 489, 553 Argon, 489 Aromatic, 390, 489, 533, 548 Arterial, 489, 538 Arteries, 489, 492, 500, 525 Arterioles, 489, 492, 493 Artery, 274, 489, 500, 519, 539, 543, 552 Aspiration, 274, 489 Assay, 309, 337, 489, 516 Astringent, 489, 556 Astrocytes, 489 Astrocytoma, 321, 331, 441, 489 Asymptomatic, 290, 364, 489 Asynchronous, 489 Ataxia, 441, 490, 550 Atrophy, 441, 490 Autoantibodies, 490 Autoantigens, 333, 339, 490 Autoimmune disease, 311, 329, 490 Autologous, 28, 296, 321, 327, 337, 345, 353, 426, 427, 490, 532 Autologous tumor cells, 337, 490 Autopsy, 25, 490
B Bacteria, 275, 419, 484, 487, 488, 490, 506, 508, 509, 525, 534, 541, 547, 552, 554 Bacterial Infections, 341, 490 Bacterial Physiology, 484, 490 Bactericidal, 490, 554 Bacteriophage, 490, 534, 552 Barbiturate, 490, 550 Basal Cell Nevus Syndrome, 304, 490 Basal cells, 490, 528 Basal Ganglia, 490, 510 Basal Ganglia Diseases, 490 Base, 17, 304, 326, 397, 490, 491, 502, 511, 520, 525 Basement Membrane, 351, 365, 491, 508, 520 Benzoic Acid, 306, 491 Beta carotene, 17, 257, 491 Bile, 491, 495, 510, 515, 519, 521, 539 Bile duct, 491, 495, 539 Bile Pigments, 491, 519 Binding Sites, 336, 351, 491 Bioassay, 325, 491 Biochemical, 261, 263, 306, 324, 337, 338, 390, 486, 488, 491, 521, 532 Biological response modifier, 258, 300, 302, 319, 491, 518 Biological therapy, 283, 286, 287, 291, 292, 459, 491, 512 Biomarkers, 18, 260, 491 Biotechnology, 124, 380, 420, 433, 440, 441, 442, 491 Biotic, 492, 554 Bladder, 492, 499, 538, 554 Blood pressure, 278, 492, 526, 546 Blood vessel, 40, 277, 350, 382, 487, 492, 495, 506, 519, 522, 524, 532, 546, 548, 550, 551, 552, 555 Body Fluids, 491, 492, 504, 546, 553 Body Regions, 21, 492 Bone scan, 492, 544 Boron, 264, 342, 492 Boron Neutron Capture Therapy, 264, 342, 492 Bowel, 486, 492, 503, 518, 521, 548 Bowel Movement, 492, 503, 548 Brachytherapy, 492, 518, 519, 540, 556 Brain metastases, 290, 492 Branch, 253, 254, 411, 412, 477, 492, 501, 511, 522, 531, 533, 539, 547, 551 Breast Self-Examination, 492, 545 Broad-spectrum, 35, 37, 394, 492
Index 559
Bronchi, 492, 507, 552 Buccal, 327, 492, 522 Burns, 30, 385, 410, 492, 493, 551 Burns, Electric, 492, 493 C Caffeine, 493, 539 Calcium, 493, 498, 523, 545 Callus, 493, 505, 520, 530 Cancer vaccine, 314, 339, 341, 356, 493, 524, 553 Capillary, 362, 493, 543, 555 Carbohydrate, 493, 500, 535 Carbon Dioxide, 438, 493, 542, 554 Carcinoembryonic Antigen, 493 Carcinogen, 453, 493, 524, 527 Carcinogenesis, 252, 327, 370, 390, 493, 495, 551 Carcinogenic, 306, 390, 486, 493, 497, 517, 528, 530, 537, 553, 554 Cardiac, 281, 294, 304, 493, 505, 507, 513, 527 Carmustine, 288, 324, 325, 326, 424, 493 Carotene, 17, 260, 491, 493 Carotenoids, 252, 264, 416, 491, 493 Case report, 494, 496 Case series, 494, 496 Case-Control Studies, 36, 494, 506 Castor Oil, 494, 543 Cataracts, 34, 494 Catheter, 276, 277, 494, 519 Causal, 17, 304, 352, 389, 494, 506 Cause of Death, 309, 333, 338, 342, 364, 366, 369, 370, 494 Caustic, 494 Cell Death, 311, 369, 489, 494 Cell Differentiation, 125, 494, 545 Cell Division, 441, 490, 494, 501, 512, 524, 525, 534, 547 Cell Extracts, 321, 494 Cell membrane, 372, 421, 494, 502, 533 Cell proliferation, 327, 335, 365, 494, 542, 545 Cell Survival, 494, 512 Cell Transplantation, 281, 494 Central Nervous System, 469, 483, 493, 494, 510, 512 Cerebellar, 490, 494, 541 Cerebral, 490, 495, 507 Cerebral Cortex, 490, 495 Cerebrum, 495, 553 Cervical, 265, 343, 464, 495 Cervix, 495
Cesium, 495 Checkup, 276, 495 Cheilitis, 454, 495 Chemopreventive, 260, 263, 495 Chemotactic Factors, 495, 498 Chemotherapeutic agent, 324, 325, 326, 495 Chest wall, 495 Child Care, 495 Chin, 495, 524 Chlorine, 495 Chlorofluorocarbons, 394, 495 Cholangiography, 495, 539 Cholesterol, 327, 491, 495, 550 Choline, 344, 496 Chondrocytes, 496, 509 Chondrosarcoma, 367, 496 Choroid, 291, 295, 481, 496, 542 Chromatin, 489, 496 Chromosomal, 254, 304, 307, 308, 309, 352, 354, 355, 486, 496, 534, 543 Chromosome, 27, 307, 308, 353, 354, 398, 496, 521, 522, 544 Chronic, 16, 19, 30, 35, 281, 304, 352, 372, 385, 389, 391, 434, 435, 441, 449, 453, 455, 456, 464, 483, 496, 503, 506, 517, 520, 522, 535, 539, 549 Chronic renal, 496, 535 Ciliary, 291, 295, 496, 545 Ciliary Body, 291, 295, 496, 545 Ciliary processes, 496 Cirrhosis, 467, 496 CIS, 17, 254, 447, 496 Cisplatin, 253, 256, 324, 325, 326, 335, 426, 496 Clear cell carcinoma, 496, 503 Clinical Medicine, 496, 536 Clinical study, 496 Clone, 125, 496 Cloning, 125, 348, 372, 491, 497 Clot Retraction, 497, 534 Coagulation, 493, 497, 520, 551 Coal, 390, 391, 497 Coal Tar, 390, 391, 497 Cocarcinogenesis, 390, 497 Coccidioidomycosis, 497 Codon, 497, 511 Coenzyme, 497, 520 Cofactor, 497, 528, 538, 551 Cohort Studies, 27, 497, 506 Colchicine, 497, 553
560 Skin Cancer
Collagen, 351, 486, 491, 497, 498, 508, 509, 523, 537, 547 Collagenases, 351, 498 Colon, 265, 278, 279, 322, 341, 441, 493, 498, 520 Colorectal, 265, 353, 356, 464, 498 Combination chemotherapy, 288, 418, 498 Communis, 494, 498, 543 Complement, 303, 312, 313, 358, 368, 487, 498, 511, 523 Complementary and alternative medicine, 257, 270, 498 Complementary medicine, 257, 498 Complementation, 498 Complete remission, 498, 542 Complete response, 324, 325, 326, 498 Compliance, 9, 408, 499 Compound nevus, 402, 499 Compress, 499, 552 Computational Biology, 433, 440, 499 Computed tomography, 273, 499, 544 Computerized tomography, 499 Conception, 499, 509, 547, 548 Concomitant, 323, 499 Confounding, 36, 401, 405, 499 Congenita, 499, 505 Congestion, 499, 507 Congestive heart failure, 499, 551 Conjugated, 337, 345, 427, 491, 499 Connective Tissue, 492, 497, 499, 502, 509, 522, 524, 538, 543 Connective Tissue Cells, 499 Constriction, 499, 519, 543, 555 Consumption, 499, 503, 510, 529, 542 Contamination, 341, 499 Continuum, 308, 354, 435, 499 Contraindications, ii, 499 Control group, 9, 16, 36, 499, 541 Controlled study, 500 Conventional therapy, 500 Conventional treatment, 293, 300, 302, 500 Cooperative group, 31, 500 Cornea, 487, 500, 544, 548 Corneum, 126, 500, 507 Coronary, 500, 525, 551 Coronary Thrombosis, 500, 525 Cortex, 500, 530, 541 Corticosteroid, 500, 536 Cortisone, 500, 503 Cranial, 480, 500, 512, 528 Criterion, 388, 500 Cross-Sectional Studies, 500, 506
Croton Oil, 390, 500 Cryosurgery, 23, 25, 40, 344, 378, 380, 438, 450, 451, 452, 454, 455, 461, 501 Cryotherapy, 4, 501 Cultured cell line, 28, 501 Curative, 3, 305, 501, 551 Curettage, 4, 23, 40, 344, 422, 438, 450, 451, 455, 461, 501 Curette, 501 Cyclic, 493, 501, 537 Cyclin, 348, 349, 360, 372, 501 Cyclin-Dependent Kinases, 348, 349, 372, 501 Cyclophosphamide, 267, 345, 501 Cyclosporine, 501 Cytogenetics, 501, 543 Cytokine, 319, 346, 356, 501, 518, 543, 551 Cytoplasm, 489, 494, 501, 512, 526 Cytotoxic, 293, 303, 310, 312, 313, 323, 325, 327, 331, 347, 357, 358, 368, 501, 540, 546 Cytotoxic chemotherapy, 293, 501 Cytotoxicity, 303, 310, 496, 501 D Dacarbazine, 324, 325, 326, 369, 424, 501 Data Collection, 436, 501 Daunorubicin, 424, 501, 504 De novo, 347, 501 Degenerative, 502, 514 Deletion, 304, 308, 352, 361, 489, 502, 522 Delivery of Health Care, 502, 513 Dementia, 483, 502 Denaturation, 502, 535 Dendrites, 502, 528 Dendritic, 292, 293, 502, 524 Dendritic cell, 292, 293, 502 Denileukin diftitox, 287, 502 Density, 20, 310, 312, 313, 356, 358, 360, 388, 398, 417, 502, 530 Dentists, 40, 502 Deoxyribonucleic, 390, 502 Deoxyribonucleic acid, 390, 502 Deoxyribonucleotides, 502 Depigmentation, 502, 556 Depolarization, 502, 545 Dermal, 502, 505 Dermatitis, 258, 265, 266, 412, 502 Dermatologist, 12, 15, 21, 30, 32, 35, 36, 362, 395, 401, 404, 411, 502 Dermis, 334, 343, 499, 502, 519, 550 Desiccation, 451, 502 Detoxification, 347, 502 Developed Countries, 395, 502
Index 561
Dexamethasone, 349, 503 Diagnostic procedure, 293, 299, 322, 332, 420, 503, 545 Dialysate, 503, 504 Diarrhea, 311, 503 Diarrhoea, 503, 510 Diathesis, 503 Diclofenac, 343, 451, 503 Diclofenac Sodium, 343, 503 Diethylstilbestrol, 390, 503 Difluoromethylornithine, 253, 503 Digestion, 491, 492, 503, 518, 521, 548 Digestive system, 298, 503 Digestive tract, 503, 546, 548 Digital rectal examination, 21, 503 Dilatation, 503, 536 Dimethyl, 305, 324, 325, 326, 503 Diploid, 498, 503, 534 Direct, iii, 31, 124, 284, 348, 360, 372, 423, 435, 452, 496, 503, 541 Discoid, 391, 503 Disease Progression, 282, 347, 503 Dissection, 38, 39, 376, 451, 503 Dissociation, 485, 503, 519 Diuresis, 493, 504 Dorsal, 504, 528, 535 Double-blind, 260, 504 Doxorubicin, 504 Drug Design, 417, 425, 426, 504 Drug Interactions, 425, 504 Drug Resistance, 347, 504 Drug Tolerance, 504, 551 Duct, 504, 508, 530, 543, 550 Dwell time, 369, 504 Dyes, 305, 504 Dysplasia, 265, 442, 504 Dysplastic nevi, 32, 37, 323, 385, 398, 400, 407, 411, 458, 459, 504 Dysplastic nevus, 385, 386, 400, 408, 460, 504 Dystrophy, 441, 505 E Ectoderm, 505, 528 Ectodermal Dysplasia, 505 Ectopic, 327, 505 Effector, 303, 333, 338, 366, 483, 498, 505 Effector cell, 303, 505 Efficacy, 12, 17, 22, 280, 282, 346, 385, 386, 387, 390, 395, 404, 504, 505 Elastic, 505, 549, 552 Elasticity, 505, 546 Elastin, 497, 505, 508
Elective, 39, 126, 505 Electrocardiogram, 273, 276, 277, 278, 281, 284, 294, 505 Electrode, 505 Electrodesiccation, 23, 344, 422, 451, 461, 505 Electrolyte, 500, 505, 513, 535, 546 Elementary Particles, 505, 528, 538, 540 Emaciation, 483, 505 Embryo, 494, 505, 517, 529, 535 Embryogenesis, 328, 364, 505 Emetic, 500, 505 Emollient, 505, 525, 529 Encapsulated, 261, 505 Endemic, 506, 547 Endogenous, 322, 344, 490, 506, 552, 554 Endopeptidases, 506, 538 Endostatin, 417, 426, 506 Endothelial cell, 506, 509, 551 Endotoxin, 506, 553 End-stage renal, 496, 506, 535 Environmental Exposure, 506, 529 Environmental Health, 17, 259, 432, 434, 506 Enzymatic, 330, 359, 390, 486, 493, 498, 501, 506, 514, 535 Epidemic, 3, 7, 16, 18, 26, 326, 346, 412, 453, 506, 547 Epidemiologic Studies, 12, 27, 334, 381, 506 Epidermal, 125, 322, 327, 364, 506, 514, 520, 524, 555 Epidermal Growth Factor, 322, 506, 514 Epidermal growth factor receptor, 506, 514 Epidermodysplasia Verruciformis, 507 Epidermoid carcinoma, 260, 507, 548 Epigastric, 507, 531 Epinephrine, 426, 485, 507, 528, 554 Episode of Care, 507 Epithelial, 280, 323, 484, 496, 506, 507, 514, 520, 531 Epithelial Cells, 323, 506, 507, 514, 520 Epithelioma, 507 Epithelium, 491, 507, 519, 531 Epitope, 302, 309, 312, 313, 357, 507 Erythema, 372, 391, 507, 549 Erythrocytes, 487, 492, 507 Esophagus, 503, 507, 548 Essential Tremor, 441, 507 Estrogen, 507, 544, 550 Ethnic Groups, 385, 507
562 Skin Cancer
Etretinate, 483, 507 Excipient, 343, 507 Excisional, 28, 386, 451, 452, 454, 508, 556 Excisional biopsy, 28, 386, 508 Exocrine, 508, 531 Exogenous, 506, 508, 510 Extensor, 508, 539, 556 External-beam radiation, 508, 519, 540, 556 Extracellular, 312, 313, 351, 357, 358, 368, 489, 499, 508, 509, 523, 546 Extracellular Matrix, 351, 499, 508, 509, 523 Extracellular Matrix Proteins, 508, 523 Extracellular Space, 508 Extraction, 391, 508 Extraocular, 295, 508 Extravasation, 508 Eye Color, 391, 404, 460, 508 Eye Infections, 484, 508 Eye socket, 508, 532 F Facial, 253, 508 Family Planning, 433, 508 Family Practice, 5, 7, 508 Fat, 489, 491, 492, 493, 500, 508, 521, 546, 549 Fatigue, 467, 508 Fatty acids, 508, 537 Feces, 493, 509, 548 Fetus, 509, 516, 554 Fibrin, 497, 509, 534, 551 Fibrinogen, 509, 534, 551 Fibroblast Growth Factor, 346, 509 Fibroblasts, 328, 364, 499, 509, 547 Fibrosis, 442, 509, 544 Filtration, 341, 509 Fine-needle aspiration, 509, 527 Flavopiridol, 289, 509 Fluorescence, 509 Fluorine, 495, 509 Fluorouracil, 4, 268, 451, 509 Fold, 21, 26, 28, 434, 451, 458, 509 Follicles, 509 Folliculitis, 487, 509 Follow-Up Studies, 285, 509 Forearm, 492, 509 Fractionation, 325, 509 Free Radicals, 488, 503, 509 Fungi, 488, 508, 510, 525, 547, 556 Fungistatic, 491, 510 Fungus, 497, 510, 543
G Gallate, 260, 262, 510 Gallbladder, 483, 503, 510, 539 Gamma Rays, 510, 527, 540 Ganglion, 510, 528 Ganglioside, 28, 301, 330, 333, 338, 366, 510 Gas, 489, 493, 495, 509, 510, 515, 527, 528, 549, 555 Gastric, 506, 510, 514 Gastrin, 510, 514 Gastroenteritis, 311, 510 Gastrointestinal, 493, 507, 510, 549, 553 Gastrointestinal tract, 493, 510, 553 Gene, 124, 125, 126, 252, 282, 304, 308, 315, 316, 317, 318, 327, 335, 347, 348, 349, 352, 359, 364, 367, 370, 371, 372, 380, 386, 398, 419, 427, 441, 442, 443, 484, 486, 491, 510, 511, 521, 529, 530, 547, 552 Gene Expression, 359, 442, 510, 511, 547 Gene Targeting, 510 Gene Therapy, 315, 316, 317, 318, 336, 359, 427, 484, 511 General practitioner, 39, 392, 393, 403, 511 Genetic Code, 511, 529 Genetic Engineering, 491, 497, 511 Genetic Markers, 309, 511 Genetic testing, 511, 535 Genetics, 324, 501, 511, 531 Genital, 343, 496, 511, 556 Genotype, 511, 532 Germ Cells, 511, 547, 550 Ginseng, 269, 511 Gland, 485, 500, 511, 522, 531, 534, 538, 544, 548, 549, 550, 551 Glioma, 303, 328, 333, 338, 364, 366, 511 Glucocorticoid, 503, 511, 536 Glucose, 441, 511, 513, 518 Glutathione Peroxidase, 511, 545 Glycine, 486, 491, 511, 528, 545 Glycoprotein, 331, 493, 509, 512, 520, 551, 553 Glycosaminoglycans, 508, 512, 538 Governing Board, 512, 536 Grade, 16, 36, 436, 512 Graft, 295, 512, 514, 516, 539 Graft Rejection, 512, 516 Grafting, 450, 512 Graft-versus-host disease, 512, 539 Granulocytes, 512, 546, 556 Groin, 278, 512 Growth factors, 322, 512
Index 563
H Hair Color, 36, 376, 512 Hair follicles, 502, 509, 512 Half-Life, 337, 483, 512 Haplotypes, 512 Haptens, 485, 512 Headache, 493, 512 Health Behavior, 13, 512 Health Care Costs, 31, 380, 381, 513 Health Education, 5, 12, 17, 24, 29, 384, 403, 436, 437, 468, 513 Health Expenditures, 513 Health Fairs, 390, 470, 513 Health Policy, 16, 383, 389, 408, 513 Health Promotion, 16, 384, 406, 408, 434, 435, 449, 455, 456, 464, 513 Health Resources, v, 513, 524 Health Services, 5, 502, 513, 544 Health Status, 20, 273, 277, 512, 513 Heart Transplantation, 513 Heme, 4, 486, 513 Hemodiafiltration, 513, 554 Hemodialysis, 503, 513, 554 Hemofiltration, 513, 554 Hemoglobin, 487, 507, 513, 514 Hemoglobinopathies, 511, 514 Hemoglobinuria, 441, 514 Hemorrhage, 512, 514, 533, 539, 543, 548 Hepatic, 125, 273, 311, 514 Hepatitis, 467, 514, 555 Hepatocytes, 514 HER2/neu, 353, 514 Herbicide, 390, 514 Hereditary, 263, 393, 490, 505, 514, 542 Heredity, 483, 510, 511, 514 Herpes, 419, 514 Herpes Zoster, 514 Heterogeneity, 308, 485, 514 Histamine, 426, 487, 514 Histidine, 514 Histology, 514, 531 Homogeneous, 308, 499, 514 Homologous, 486, 511, 514, 538, 550 Hormonal, 490, 500, 514 Hormone, 393, 484, 491, 500, 503, 507, 510, 514, 517, 519, 524, 545, 547, 551 Hormone Replacement Therapy, 393, 514 Hormone therapy, 484, 514 Horny layer, 507, 514 Host, 295, 302, 318, 319, 359, 367, 410, 490, 514, 516, 554, 555 Humoral, 512, 515
Humour, 515 Hybrid, 28, 272, 496, 515 Hybridization, 348, 349, 356, 372, 515 Hybridoma, 300, 301, 322, 332, 333, 338, 366, 515 Hydrogen, 483, 491, 493, 502, 508, 511, 515, 526, 528, 529, 530, 538 Hydrolysis, 496, 515, 533, 538, 553 Hydroxides, 515 Hydroxylysine, 497, 515 Hydroxyproline, 486, 497, 515 Hyperbilirubinemia, 515, 519 Hypersensitivity, 345, 515 Hyperthermia, 278, 515 Hypertrophy, 515, 543 Hypnotic, 490, 515, 550 Hypoplasia, 505, 515 I Id, 255, 265, 342, 462, 463, 466, 476, 478, 515 Idiotype, 300, 302, 333, 338, 366, 426, 515 Imidazole, 305, 325, 326, 514, 515 Immune adjuvant, 486, 515 Immune function, 281, 515 Immune Sera, 516 Immune Tolerance, 333, 338, 356, 366, 516 Immunity, 275, 281, 337, 339, 341, 356, 483, 507, 516, 518, 552 Immunization, 292, 330, 340, 341, 345, 350, 353, 484, 516, 536 Immunoassay, 321, 331, 516 Immunodeficiency, 441, 483, 516 Immunogen, 301, 314, 315, 316, 317, 335, 340, 350, 358, 516 Immunogenic, 314, 315, 316, 317, 333, 335, 338, 339, 341, 356, 358, 366, 516 Immunoglobulin, 488, 516, 526 Immunohistochemistry, 356, 516 Immunologic, 322, 332, 339, 345, 484, 495, 516, 540 Immunology, 315, 316, 317, 321, 324, 336, 359, 484, 485, 516 Immunosuppressant, 486, 509, 516, 525 Immunosuppressive, 411, 501, 511, 516 Immunosuppressive therapy, 516 Immunotherapy, 28, 126, 278, 282, 312, 313, 314, 315, 316, 317, 318, 319, 336, 339, 357, 359, 367, 376, 452, 484, 491, 516 Immunotoxins, 310, 312, 313, 358, 368, 516, 540 Impairment, 263, 355, 490, 508, 516, 524 Implant radiation, 516, 518, 519, 540, 556
564 Skin Cancer
In situ, 392, 517 Incision, 273, 517, 518, 520 Incisional, 400, 517 Incisional biopsy, 400, 517 Indicative, 309, 377, 517, 531, 555 Indolent, 517 Induction, 124, 125, 339, 349, 517, 540 Infant Mortality, 468, 517 Infant, Newborn, 485, 517 Infarction, 500, 517, 525 Infiltrating cancer, 517, 518 Inflammation, 364, 483, 488, 495, 496, 500, 502, 508, 509, 510, 514, 517, 530, 535, 539, 543, 544 Infusion, 279, 517 Ingestion, 517, 535 Inhalation, 485, 497, 517, 535 Initiation, 274, 306, 370, 517, 552 Initiator, 517, 518 Inorganic, 252, 381, 390, 496, 515, 517 Insight, 517, 543 Insulin, 322, 517, 518, 547 Insulin-dependent diabetes mellitus, 518 Interferon-alpha, 324, 325, 326, 361, 518 Interleukin-1, 280, 285, 518 Interleukin-12, 280, 285, 518 Intermittent, 19, 30, 37, 376, 388, 407, 421, 434, 451, 518, 522, 532 Internal Medicine, 5, 8, 10, 11, 21, 342, 518 Internal radiation, 518, 519, 540, 556 Interstitial, 351, 492, 508, 518, 519, 556 Intestinal, 493, 518, 523 Intestine, 492, 518, 520 Intracellular, 314, 369, 493, 517, 518, 524, 535, 537, 545 Intraocular, 285, 290, 295, 342, 518 Intravenous, 517, 518 Intrinsic, 347, 360, 485, 491, 518 Invasive cancer, 517, 518 Involuntary, 490, 507, 518, 527 Iodine, 336, 519 Iodine-131, 336, 519 Ionization, 519 Ionizing, 40, 390, 391, 486, 506, 519, 540, 554 Ions, 491, 503, 505, 515, 519, 540 Iris, 295, 481, 487, 500, 508, 519 Irradiance, 388, 519 Irradiation, 344, 391, 395, 492, 519, 525, 528, 542, 556 Ischemia, 490, 510, 519 Isolated hepatic perfusion, 273, 519
Isolated limb perfusion, 25, 254, 261, 277, 519 Isothiocyanates, 260, 519 Isotretinoin, 519 J Jaundice, 467, 515, 519 Junctional nevus, 402, 519 K Kb, 432, 520 Keratin, 520 Keratinocytes, 365, 520 Keratoacanthoma, 520 Keratosis, 402, 451, 484, 520 Kidney Disease, 298, 432, 442, 520 Kinetic, 519, 520 L Labile, 498, 520 Lactate Dehydrogenase, 31, 520 Lag, 393, 520 Laminin, 491, 508, 520 Laparotomy, 273, 520 Large Intestine, 503, 518, 520, 541, 546 Laser Surgery, 40, 451, 455, 461, 520 Laser therapy, 450, 520 Latency, 390, 395, 520 Latent, 19, 390, 396, 520, 533, 536 Latent period, 390, 520, 533 Laxative, 485, 521, 525 Lectin, 310, 483, 521, 524 Lens, 25, 400, 494, 499, 521, 542 Lentigo, 4, 25, 307, 354, 364, 400, 402, 521 Lethal, 19, 29, 326, 389, 401, 404, 490, 521, 527, 543 Leukapheresis, 276, 281, 284, 294, 489, 521 Leukocytes, 492, 495, 512, 518, 521, 526, 553 Leukoplakia, 454, 521 Library Services, 476, 521 Life Expectancy, 27, 521 Ligament, 521, 538 Limb perfusion, 521 Linkage, 8, 360, 398, 511, 521 Lip, 521 Lipid, 427, 496, 518, 521 Liposomes, 126, 261, 521 Litter, 323, 521 Liver cancer, 467, 521 Liver metastases, 315, 316, 317, 318, 336, 521 Liver Neoplasms, 522, 555 Liver scan, 522, 544 Liver Transplantation, 522
Index 565
Local Government, 434, 463, 522 Localization, 300, 302, 345, 516, 522 Localized, 27, 254, 314, 315, 316, 317, 336, 349, 359, 505, 517, 520, 522, 530, 534, 554 Longitudinal Studies, 500, 522 Long-Term Care, 522 Loop, 351, 522 Loss of Heterozygosity, 308, 522 Lubricants, 522, 532 Lupus, 391, 522 Lymphatic, 31, 350, 459, 460, 517, 522, 524, 545, 547, 551 Lymphatic Metastasis, 522, 545 Lymphatic system, 350, 460, 522, 547, 551 Lymphocyte, 353, 483, 488, 522, 523 Lymphocyte Count, 483, 522 Lymphocytic, 522 Lymphoid, 488, 523 Lymphoma, 418, 419, 441, 502, 523 Lymphoscintigraphy, 23, 523 Lytic, 523, 545 M Macrophage, 518, 523 Magnetic Resonance Imaging, 273, 275, 278, 523, 544 Major Histocompatibility Complex, 319, 331, 512, 523 Malabsorption, 441, 523 Malignancy, 19, 40, 312, 313, 358, 367, 368, 376, 385, 389, 407, 468, 523, 531 Malignant tumor, 391, 523 Malnutrition, 490, 523, 526 Mammary, 323, 523, 550 Marital Status, 33, 523 Mass Screening, 35, 389, 523 Matrix metalloproteinase, 351, 523 Mediate, 303, 315, 316, 317, 318, 319, 325, 336, 523 Mediator, 518, 523 Medical Records, 275, 523, 543 Medically Underserved Area, 436, 524 MEDLINE, 433, 440, 442, 524 Melanin, 306, 326, 342, 349, 417, 481, 502, 519, 524, 533, 554 Melanoma vaccine, 25, 28, 280, 289, 296, 297, 339, 427, 461, 524 Melanosis, 469, 524 Melanosomes, 524 Melphalan, 277, 278, 424, 427, 524 Membrane Proteins, 521, 524 Meninges, 300, 302, 494, 524 Meningioma, 524
Mental, v, 298, 432, 439, 443, 495, 502, 504, 508, 524, 529, 533, 536, 539 Mental Disorders, 298, 524, 533, 536 Mental Health, v, 298, 432, 439, 524, 529, 536, 539 Mesenchymal, 506, 524 Meta-Analysis, 27, 524 Metabolite, 344, 483, 503, 524, 533 Metaphase, 369, 524 Metastasize, 4, 295, 323, 350, 364, 365, 370, 387, 411, 452, 461, 468, 525, 544 Metastatic cancer, 315, 316, 317, 318, 336, 365, 525 Methionine, 503, 525 Methotrexate, 269, 525 Methoxsalen, 525 MI, 356, 369, 371, 427, 481, 525 Microbe, 525, 552 Microbiology, 484, 490, 525 Microorganism, 497, 525, 556 Microscopy, 32, 258, 356, 362, 402, 491, 525 Microtubules, 525, 530 Migration, 352, 387, 525 Milk Thistle, 269, 525, 546 Milligram, 337, 525 Milliliter, 306, 525 Millimeter, 386, 451, 457, 461, 525 Mineral Oil, 391, 497, 525 Mitosis, 489, 525, 547 Modeling, 22, 504, 526 Modification, 486, 511, 526, 539 Monitor, 281, 284, 325, 493, 526, 529, 555 Monocytes, 292, 518, 521, 526, 551 Mononuclear, 314, 526, 553 Morale, 437, 526 Morphogenesis, 367, 526 Morphological, 485, 505, 510, 524, 526 Morphology, 362, 367, 526 Motion Sickness, 526, 527 Motivations, 437, 526 Mucosa, 522, 526 Multiphasic Screening, 390, 526 Muscle Fibers, 526 Muscular Atrophy, 441, 526 Muscular Dystrophies, 505, 527 Mustard Gas, 527 Mutagen, 527 Mutagenic, 486, 527, 528, 554 Myelodysplastic syndrome, 280, 527, 546 Myeloma, 301, 515, 527 Myeloproliferative Disorders, 281, 527 Myocardium, 525, 527
566 Skin Cancer
Myotonic Dystrophy, 441, 527 Myristate, 327, 527 N Naive, 361, 527 Natural killer cells, 518, 527 Nausea, 310, 467, 510, 527 Needle biopsy, 285, 509, 527 Neonatal, 517, 527 Neoplasia, 327, 364, 369, 441, 507, 527 Neoplasm, 3, 281, 292, 295, 307, 315, 316, 317, 336, 354, 359, 385, 507, 522, 527, 531, 543, 545, 553 Neoplastic, 333, 338, 366, 492, 520, 522, 523, 527, 530 Nephropathy, 520, 527 Nerve, 310, 312, 313, 358, 485, 487, 490, 495, 502, 510, 523, 528, 535, 542, 544, 548, 552 Nerve Growth Factor, 310, 312, 313, 358, 528 Nervous System, 441, 494, 523, 528, 549, 550 Neural, 310, 312, 313, 328, 358, 365, 515, 528 Neural Crest, 310, 312, 313, 358, 528 Neuroblastoma, 333, 338, 366, 528 Neuronal, 528 Neurons, 502, 528, 550 Neurotransmitter, 483, 484, 486, 511, 514, 528, 545, 549 Neutron Capture Therapy, 342, 528 Neutrons, 486, 492, 519, 528, 540 Nickel, 258, 528 Nitrogen, 25, 343, 485, 489, 501, 508, 524, 528, 553 Nitrosamines, 391, 528 Nonmelanoma skin cancer, 6, 14, 16, 17, 18, 19, 23, 252, 253, 257, 259, 264, 344, 375, 381, 385, 388, 389, 390, 417, 418, 438, 453, 528 Non-small cell lung cancer, 280, 528 Notochord, 328, 365, 529 Nuclear, 252, 261, 294, 336, 391, 490, 510, 529, 536, 540, 542, 554 Nuclear Medicine, 261, 294, 336, 529 Nuclei, 486, 511, 523, 525, 528, 529, 538 Nucleic Acid Hybridization, 515, 529 Nucleus, 357, 489, 490, 496, 501, 505, 510, 526, 528, 529, 538, 548, 550 Nurse Practitioners, 5, 15, 529 Nutritional Status, 391, 529
O Occult, 38, 529 Occupational Exposure, 529 Occupational Health, 405, 529 Ocular, 273, 294, 398, 529 Odds Ratio, 6, 395, 529, 542 Odour, 489, 529 Office Visits, 21, 272, 529 Ointments, 529, 531, 556 Oncogene, 318, 328, 335, 357, 364, 441, 529 Oncogenic, 323, 333, 338, 340, 350, 366, 530, 538 Oncolysis, 530 Oncolytic, 369, 530 Opacity, 494, 502, 530 Opportunistic Infections, 483, 530 Orbit, 508, 530, 532 Orbital, 498, 530 Organ Transplantation, 530 Organelles, 501, 524, 526, 530 Organogenesis, 351, 530 Orofacial, 40, 530 Osteomyelitis, 391, 530 Outpatient, 33, 403, 507, 530 Ovarian epithelial cancer, 280, 530 Ovaries, 530, 545 Oxidation, 483, 488, 511, 530 P P53 gene, 530 Paclitaxel, 261, 263, 269, 368, 369, 530 Palladium, 336, 337, 530 Palliative, 25, 305, 530, 531, 551 Palliative therapy, 25, 531 Pancreas, 353, 483, 491, 503, 517, 531, 553 Pancreatic, 258, 441, 531 Pancreatic cancer, 258, 441, 531 Papilloma, 343, 507, 531, 543 Papillomavirus, 514, 531 Papule, 16, 531 Paraffin, 531 Paroxysmal, 441, 531 Partial remission, 531, 542 Partnership Practice, 531, 536 Patch, 350, 452, 462, 521, 531 Pathogenesis, 19, 28, 531 Pathologic, 31, 339, 489, 491, 500, 515, 531, 539, 555 Pathologic Processes, 489, 531 Pathologies, 327, 364, 531 Pathologist, 355, 400, 531 Patient Advocacy, 467, 531
Index 567
Patient Education, 4, 19, 32, 377, 387, 409, 412, 450, 451, 468, 474, 476, 481, 531 PDQ, 447, 449, 531 Pediatrics, 30, 532 Pelvic, 532, 538 Pelvis, 273, 278, 483, 530, 532, 554 Perceived risk, 10, 12, 30, 532 Perception, 20, 532 Perennial, 532, 553 Perfusion, 254, 273, 277, 532 Perianal, 532 Periorbital, 532 Peripheral blood, 285, 288, 289, 293, 314, 518, 532, 536 Peripheral stem cell transplantation, 281, 532 Peritoneal, 503, 504, 532 Peritoneal Dialysis, 503, 504, 532 Petroleum, 391, 525, 531, 532 Pharmacists, 532 Pharmacodynamics, 369, 532 Pharmacokinetic, 283, 532 Pharmacologic, 487, 500, 512, 532, 552 Phenotype, 6, 124, 319, 347, 348, 365, 371, 372, 398, 458, 498, 532 Phenyl, 260, 532 Phenylalanine, 269, 533, 553 Phorbol, 327, 533 Phospholipases, 533, 545 Phospholipids, 508, 533 Phosphorus, 493, 533 Phosphorylated, 357, 497, 533 Phosphorylation, 361, 501, 533 Photoallergy, 533 Photobiology, 17, 259, 262, 533 Photodynamic therapy, 4, 126, 257, 262, 282, 451, 533 Photophobia, 533 Photosensitivity, 389, 391, 533, 556 Photosensitivity Disorders, 389, 533 Photosensitizing Agents, 533 Phototherapy, 453, 533 Physician Assistants, 5, 9, 10, 533 Physiologic, 485, 512, 534, 537, 541 Physiology, 258, 259, 323, 349, 534 Phytotoxin, 534, 543 Pigmentation, 17, 337, 364, 389, 395, 524, 534 Pigments, 491, 493, 534 Pilot study, 30, 534 Pitch, 391, 534 Pituitary Gland, 500, 509, 534
Plants, 493, 496, 511, 514, 521, 525, 526, 534, 535, 536, 543, 547, 552, 553 Plaque, 16, 364, 534 Plasma, 253, 276, 277, 281, 284, 294, 308, 488, 494, 509, 513, 521, 527, 534, 535, 545 Plasma cells, 488, 527, 534 Plasmapheresis, 277, 295, 489, 534 Plasmid, 353, 534, 555 Plasmin, 351, 534 Plasminogen, 126, 351, 534 Plasminogen Activators, 534 Platelet Activation, 534, 546 Plateletpheresis, 489, 534 Platelets, 276, 284, 294, 534, 535, 543, 551 Platinum, 496, 522, 530, 535 Pneumonia, 499, 535 Poisoning, 8, 510, 527, 535 Pollen, 535, 539 Polycyclic Hydrocarbons, 390, 535 Polycystic, 442, 535 Polymerase, 38, 309, 326, 328, 535 Polymerase Chain Reaction, 38, 309, 326, 328, 535 Polymorphism, 308, 535 Polysaccharide, 311, 485, 488, 535, 538 Polyvalent, 339, 341, 535 Posterior, 486, 490, 496, 504, 519, 531, 535, 544 Postnatal, 535, 548 Postsynaptic, 535, 545 Potassium, 535 Potassium hydroxide, 535 Potentiates, 518, 536 Potentiation, 536, 546 Power Plants, 391, 536 Practice Guidelines, 39, 439, 462, 463, 536 Precancerous, 381, 389, 451, 453, 454, 484, 495, 536 Precursor, 362, 402, 403, 454, 489, 491, 496, 501, 505, 506, 533, 534, 536, 553, 554 Predisposition, 16, 360, 536 Prednisolone, 536 Preleukemia, 527, 536, 546 Premalignant, 4, 355, 536 Presumptive, 536 Prevalence, 304, 388, 389, 529, 536 Prickle, 520, 536 Primary tumor, 25, 33, 326, 347, 355, 536 Private Practice, 381, 536 Private Sector, 436, 536 Probe, 307, 354, 355, 536 Professional Practice, 436, 537
568 Skin Cancer
Prognostic factor, 31, 350, 537 Program Development, 396, 537 Progression, 263, 283, 308, 310, 312, 313, 318, 349, 357, 361, 367, 385, 487, 501, 537, 553 Progressive, 17, 294, 304, 352, 365, 367, 494, 496, 502, 504, 512, 527, 534, 537, 553 Proline, 497, 515, 537 Promoter, 359, 361, 390, 537 Prone, 411, 537 Proneness, 537 Prophylaxis, 507, 537, 554 Prospective Studies, 7, 537 Prospective study, 537 Prostaglandin, 343, 537 Prostaglandins A, 537 Prostate, 266, 312, 313, 353, 357, 367, 368, 441, 464, 491, 538, 553 Prostatic acid phosphatase, 353, 538 Protease, 306, 538 Protease Inhibitors, 306, 538 Protective Clothing, 4, 13, 17, 22, 27, 37, 385, 386, 387, 390, 396, 399, 400, 410, 411, 421, 435, 452, 454, 456, 458, 459, 538 Protein C, 341, 486, 490, 497, 520, 538 Protein Conformation, 486, 520, 538 Protein S, 292, 311, 334, 380, 442, 491, 511, 538 Proteoglycan, 125, 302, 538 Proteolytic, 306, 314, 498, 509, 534, 538, 543 Protons, 486, 515, 519, 538, 540 Proto-Oncogene Proteins, 530, 538 Proto-Oncogene Proteins c-mos, 530, 538 Proto-Oncogenes, 304, 335, 352, 538 Proxy, 405, 539 Pruritic, 539, 544 Psoralen, 28, 376, 453, 539 Psychic, 524, 539, 544 PTC, 304, 328, 352, 364, 539 Public Policy, 433, 539 Pulmonary, 125, 260, 492, 495, 499, 513, 539, 549 Pulmonary Artery, 492, 539 Pulse, 526, 539 Purifying, 345, 539 Purines, 539, 545 Purpura, 539 Pyogenic, 530, 539 Pyrazoloacridine, 295, 539 Pyrimidines, 539, 545
Q Quality of Life, 531, 539, 549 Quercetin, 260, 539 Quiescent, 540, 556 R Race, 19, 37, 323, 384, 392, 524, 525, 540 Racemic, 524, 540 Radiation, Ionizing, 17, 540 Radioactive, 278, 321, 391, 492, 512, 515, 516, 518, 519, 522, 523, 526, 529, 530, 540, 544, 553, 554, 556 Radioactivity, 337, 540 Radiodermatitis, 454, 540 Radioimmunotherapy, 540 Radiolabeled, 337, 519, 540, 556 Radiology, 529, 540 Radium, 540 Random Allocation, 540, 541 Randomization, 14, 36, 541 Randomized Controlled Trials, 17, 541 Reactivation, 541 Reactive Oxygen Species, 28, 541 Reagent, 337, 495, 541 Recombinant, 324, 325, 326, 340, 344, 348, 349, 350, 369, 372, 426, 427, 541, 555 Recombination, 511, 541 Rectal, 541 Rectum, 488, 492, 498, 503, 510, 520, 538, 541 Recur, 355, 541 Red Nucleus, 490, 541 Reductase, 525, 541 Refer, 1, 15, 347, 435, 492, 498, 510, 514, 522, 527, 528, 540, 541, 552 Refraction, 541, 547 Refractory, 281, 282, 365, 369, 542 Regeneration, 509, 542 Regimen, 37, 277, 281, 285, 288, 295, 368, 369, 418, 505, 542 Regional lymph node, 25, 28, 350, 376, 451, 542 Registries, 27, 33, 391, 405, 464, 542 Relapse, 282, 363, 542 Relative risk, 18, 384, 483, 542 Reliability, 20, 405, 542 Remission, 278, 333, 338, 366, 541, 542 Repopulation, 542 Resection, 333, 338, 343, 366, 542 Resolving, 308, 354, 542 Respiration, 493, 526, 542 Response rate, 283, 324, 325, 326, 369, 542 Restoration, 541, 542, 556
Index 569
Retina, 481, 496, 521, 542, 543, 545 Retinoblastoma, 361, 441, 542 Retinoblastoma Protein, 361, 542 Retinoid, 252, 253, 254, 483, 507, 543 Retinol, 254, 260, 543 Retrospective, 306, 307, 354, 543 Retrospective study, 307, 354, 543 Retroviral vector, 511, 543 Rhinophyma, 543 Rhizoxin, 254, 543 Ricin, 310, 311, 543 Risk patient, 13, 14, 21, 25, 32, 34, 543 Rod, 529, 543 Role Playing, 6, 543 Rubber, 484, 543 Rutin, 539, 543 S Saccharin, 390, 543 Salivary, 503, 531, 543, 549 Salivary glands, 503, 543 Sarcoma, 18, 261, 279, 340, 351, 382, 543, 546 Sargramostim, 285, 287, 288, 289, 543 Satellite, 31, 33, 543 Scabies, 412, 544 Scans, 273, 276, 277, 278, 281, 284, 294, 544 Scatter, 334, 337, 544, 554 School Health Services, 5, 544 Sclera, 496, 544 Sclerosis, 441, 544 Scrotum, 381, 544, 550 Sebaceous, 502, 543, 544 Sebaceous gland, 502, 543, 544 Secondary tumor, 18, 525, 544 Secretion, 315, 316, 317, 318, 336, 483, 500, 506, 514, 515, 518, 544, 545 Secular trends, 544 Sedative, 346, 490, 544 Sedatives, Barbiturate, 544 Sedimentation, 544, 553 Seizures, 488, 531, 544 Selective estrogen receptor modulator, 544, 550 Selenium, 17, 253, 256, 545 Semen, 538, 545 Senile, 484, 521, 545 Sentinel Lymph Node Biopsy, 31, 545 Sequencing, 535, 545 Serine, 306, 351, 506, 538, 545, 553 Serologic, 282, 339, 516, 545 Serrata, 496, 545 Sex Characteristics, 484, 545
Sex Determination, 441, 545 Shock, 283, 426, 545, 553 Signal Transduction, 328, 364, 545 Signs and Symptoms, 38, 40, 458, 542, 546 Silymarin, 253, 260, 261, 263, 525, 546 Skeletal, 490, 527, 546 Skeleton, 537, 546 Skin Abnormalities, 362, 546 Skin Aging, 19, 546 Skin graft, 342, 355, 480, 546 Skin Neoplasms, 4, 507, 546 Skin Pigmentation, 395, 546 Small cell lung cancer, 546 Small intestine, 514, 518, 546, 553 Smoldering leukemia, 527, 546 Smooth muscle, 487, 493, 499, 514, 546, 549 Social Class, 386, 398, 546 Social Environment, 5, 539, 546 Social Security, 541, 546 Sodium, 341, 503, 546, 550 Soft tissue, 279, 333, 338, 366, 492, 546, 551 Soft tissue sarcoma, 279, 333, 338, 366, 546 Solar radiation, 4, 383, 387, 547 Solid tumor, 309, 333, 338, 366, 487, 504, 506, 547 Soma, 547 Somatic, 484, 505, 515, 526, 530, 547 Somatic mutations, 547 Somatomedins, 322, 547 Somatotropin, 547 Specialist, 467, 470, 547 Specificity, 15, 301, 302, 310, 314, 321, 337, 357, 387, 408, 485, 506, 536, 547 Spectrum, 17, 36, 395, 396, 421, 459, 466, 547, 554 Sperm, 496, 535, 547, 550, 553 Spina bifida, 490, 547 Spinal cord, 489, 494, 496, 510, 524, 528, 547 Spinous, 507, 520, 547 Spleen, 515, 522, 547 Sporadic, 304, 327, 352, 364, 542, 547 Spores, 497, 547 Squamous cells, 528, 548 Staff Development, 22, 548 Staging, 25, 28, 31, 38, 308, 363, 376, 468, 544, 548 Statistically significant, 38, 548 Stem cell transplantation, 281, 296, 548 Stem Cells, 292, 296, 512, 532, 548 Sterility, 501, 548
570 Skin Cancer
Sterilization, 391, 548 Stimulant, 493, 514, 548 Stimulus, 505, 520, 548 Stomach, 483, 503, 507, 510, 514, 527, 546, 547, 548 Stool, 498, 520, 548 Strand, 535, 548 Stress, 281, 294, 327, 480, 510, 527, 536, 543, 548 Stroke, 298, 432, 548 Stroma, 351, 519, 548 Styrene, 543, 548 Subacute, 517, 549 Subclinical, 309, 517, 544, 549 Subcutaneous, 350, 549 Submaxillary, 506, 549 Subspecies, 547, 549 Substance P, 524, 544, 549 Substrate, 367, 549 Subungual, 364, 402, 549 Suction, 509, 549 Sun protection factor, 17, 34, 35, 400, 405, 435, 451, 454, 549 Sunscreening Agents, 390, 421, 549 Supplementation, 257, 549 Support group, 261, 376, 468, 469, 480, 481, 549 Supportive care, 531, 549 Suppression, 17, 34, 318, 348, 351, 369, 372, 376, 500, 549 Suppressive, 318, 349, 549 Surfactant, 341, 549 Survival Rate, 29, 324, 325, 326, 362, 369, 388, 399, 401, 549 Sweat, 502, 550 Sweat Glands, 502, 550 Sympathomimetic, 507, 550 Symphysis, 495, 538, 550 Symptomatic, 347, 396, 550 Synaptic, 528, 546, 550 Synergistic, 17, 550 Systemic, 273, 315, 316, 317, 318, 336, 359, 369, 389, 424, 460, 463, 492, 507, 517, 519, 536, 540, 550, 552, 556 T Tamoxifen, 324, 325, 326, 424, 545, 550 Tax Exemption, 405, 550 Telangiectasia, 441, 550 Temozolomide, 274, 290, 427, 550 Teratogenic, 486, 507, 519, 550 Terminator, 497, 550 Testicles, 544, 550
Testicular, 545, 550 Testis, 328, 550 Thalamic, 490, 550 Thalamic Diseases, 490, 550 Thalidomide, 289, 290, 346, 550 Therapeutics, 330, 425, 551 Thermal, 492, 503, 528, 535, 551 Thigh, 277, 281, 284, 294, 512, 551 Thiouracil, 342, 551 Thorax, 483, 551 Threonine, 538, 545, 551 Thrombin, 509, 538, 551 Thrombocytes, 535, 551 Thrombolytic, 534, 551 Thrombomodulin, 538, 551 Thrombosis, 538, 548, 551 Thymus, 516, 522, 551 Thyroid, 519, 551, 554 Tin, 400, 535, 551 Tissue, 261, 274, 275, 276, 277, 279, 281, 284, 294, 312, 313, 320, 322, 327, 332, 342, 343, 350, 353, 357, 364, 382, 486, 487, 488, 489, 490, 491, 492, 493, 495, 496, 497, 499, 501, 502, 504, 505, 506, 508, 509, 510, 512, 514, 515, 516, 517, 518, 520, 521, 522, 523, 524, 526, 527, 528, 530, 532, 533, 534, 535, 542, 545, 546, 547, 548, 549, 550, 551, 552, 553, 556 Tissue Expansion, 551 Tolerance, 484, 551 Tomography, 264, 278, 499, 544, 551 Tone, 12, 551 Tonus, 551 Tooth Preparation, 484, 552 Topical chemotherapy, 438, 450, 455, 552 Tourniquet, 278, 519, 521, 552 Toxicity, 124, 293, 311, 324, 325, 326, 346, 360, 391, 504, 552, 555 Toxicology, 434, 552 Toxin, 506, 516, 551, 552 Trace element, 492, 509, 528, 551, 552 Trachea, 492, 551, 552 Transcription Factors, 328, 365, 552 Transduction, 254, 262, 357, 545, 552 Transfection, 349, 491, 511, 552 Transfer Factor, 516, 552 Transferases, 552 Transgenes, 356, 552 Translation, 486, 552 Transmitter, 483, 489, 523, 552, 555 Trauma, 385, 390, 491, 512, 550, 551, 553 Treatment Failure, 553
Index 571
Trees, 369, 543, 553 Triad, 553 Triage, 6, 10, 15, 553 Trypsin, 553 Tryptophan, 497, 553 Tuberous Sclerosis, 441, 553 Tubulin, 369, 525, 553 Tumor marker, 312, 313, 357, 368, 491, 553 Tumor model, 315, 316, 317, 318, 336, 553 Tumor Necrosis Factor, 277, 551, 553 Tumor suppressor gene, 304, 319, 352, 360, 365, 398, 522, 530, 542, 553 Tumor-derived, 426, 553 Tumorigenic, 306, 348, 365, 372, 553 Tumour, 322, 330, 356, 510, 530, 553 Tyrosinase peptide, 336, 553 Tyrosine, 261, 263, 270, 312, 313, 357, 368, 553 U Ulcer, 554 Ulceration, 29, 31, 38, 554 Ultrafiltration, 341, 513, 554 Ultraviolet Rays, 23, 334, 410, 452, 454, 461, 464, 554 Unconscious, 487, 515, 554 Uranium, 391, 540, 554 Urban Population, 406, 554 Urease, 528, 554 Urethra, 538, 554 Urine, 278, 281, 284, 294, 337, 467, 492, 504, 506, 514, 554 Urokinase, 351, 554 Uterus, 495, 530, 554 V Vaccination, 276, 277, 280, 284, 294, 318, 356, 554 Vagina, 495, 503, 554, 556 Vaginal, 554, 556 Vascular, 496, 502, 517, 534, 555 Vasoconstriction, 507, 555 Vasodilator, 514, 551, 555 VE, 259, 555 Vector, 351, 359, 552, 555 Vein, 274, 275, 276, 277, 278, 281, 284, 294, 295, 518, 519, 529, 543, 555
Venous, 538, 555 Venter, 555 Ventral, 328, 365, 555 Venules, 492, 493, 555 Verruca, 555 Vertebrae, 490, 547, 555 Vertebral, 529, 547, 555 Veterinary Medicine, 433, 555 Video Recording, 409, 555 Videodisc Recording, 555 Vinblastine, 424, 553, 555 Vinca Alkaloids, 543, 555 Vincristine, 553, 555 Vinyl Chloride, 384, 555 Viral, 340, 345, 350, 385, 467, 530, 538, 552, 553, 555 Viral Hepatitis, 467, 555 Virulence, 552, 555 Virus, 275, 340, 343, 350, 419, 483, 490, 511, 514, 518, 534, 543, 552, 555 Viscera, 547, 555 Vitiligo, 266, 539, 556 Vitreous, 521, 542, 556 Vitro, 126, 257, 310, 312, 313, 321, 323, 349, 357, 358, 360, 367, 511, 517, 535, 556 Vivo, 32, 125, 257, 303, 315, 316, 317, 318, 323, 336, 349, 357, 360, 369, 511, 517, 556 Vulva, 556 Vulvar Neoplasms, 556 W War, 32, 527, 556 Wart, 520, 556 Windpipe, 551, 556 Wound Healing, 125, 342, 351, 509, 523, 556 X Xenograft, 487, 553, 556 Xeroderma Pigmentosum, 252, 254, 556 X-ray therapy, 519, 556 Y Yeasts, 510, 532, 556 Z Zinc Oxide, 334, 421, 556 Zymogen, 351, 538, 556
572 Skin Cancer
Index 573
574 Skin Cancer
