GLEEVEC 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 ©2004 by ICON Group International, Inc. Copyright ©2004 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., 1960Gleevec: 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: 0-597-84437-2 1. Gleevec-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on Gleevec. 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 GLEEVEC ................................................................................................... 3 Overview........................................................................................................................................ 3 Federally Funded Research on Gleevec .......................................................................................... 3 E-Journals: PubMed Central ....................................................................................................... 16 The National Library of Medicine: PubMed ................................................................................ 17 CHAPTER 2. NUTRITION AND GLEEVEC ......................................................................................... 35 Overview...................................................................................................................................... 35 Finding Nutrition Studies on Gleevec ......................................................................................... 35 Federal Resources on Nutrition ................................................................................................... 36 Additional Web Resources ........................................................................................................... 37 CHAPTER 3. ALTERNATIVE MEDICINE AND GLEEVEC ................................................................... 39 Overview...................................................................................................................................... 39 National Center for Complementary and Alternative Medicine.................................................. 39 Additional Web Resources ........................................................................................................... 43 General References ....................................................................................................................... 44 CHAPTER 4. CLINICAL TRIALS AND GLEEVEC ................................................................................ 45 Overview...................................................................................................................................... 45 Recent Trials on Gleevec .............................................................................................................. 45 Keeping Current on Clinical Trials ............................................................................................. 65 CHAPTER 5. PERIODICALS AND NEWS ON GLEEVEC ...................................................................... 67 Overview...................................................................................................................................... 67 News Services and Press Releases................................................................................................ 67 Academic Periodicals covering Gleevec........................................................................................ 71 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 75 Overview...................................................................................................................................... 75 NIH Guidelines............................................................................................................................ 75 NIH Databases............................................................................................................................. 77 Other Commercial Databases....................................................................................................... 79 APPENDIX B. PATIENT RESOURCES ................................................................................................. 81 Overview...................................................................................................................................... 81 Patient Guideline Sources............................................................................................................ 81 Finding Associations.................................................................................................................... 83 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 85 Overview...................................................................................................................................... 85 Preparation................................................................................................................................... 85 Finding a Local Medical Library.................................................................................................. 85 Medical Libraries in the U.S. and Canada ................................................................................... 85 ONLINE GLOSSARIES.................................................................................................................. 91 Online Dictionary Directories ..................................................................................................... 91 GLEEVEC DICTIONARY .............................................................................................................. 93 INDEX .............................................................................................................................................. 129
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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 Gleevec 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 Gleevec, 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 Gleevec, 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 Gleevec. 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 Gleevec, 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 Gleevec. 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 GLEEVEC Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Gleevec.
Federally Funded Research on Gleevec The U.S. Government supports a variety of research studies relating to Gleevec. 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 Gleevec. 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 Gleevec. The following is typical of the type of information found when searching the CRISP database for Gleevec: •
Project Title: ATTACKING ANTHRAX ACTION BY BLOCKING RECEPTOR SIGNALING Principal Investigator & Institution: Chan, Joanne; Research Associate & Instructor; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005
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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Summary: (provided by applicant): Application for R21, NOT-AI-02-023, Biodefense and Emerging Infectious Diseases Research Anthrax toxin, isolated from the bacterium, Bacillus anthracis, enters human cells and disrupts cellular function. The toxin consists of a receptor binding component, protective antigen (PA) which can associate with the enzymatic components, edema factor (EF) and/or lethal factor (LF) to form the anthrax toxin. The toxin binds a cell surface receptor which mediates the internalization of the toxin complex. Recently, work from the laboratories of John Young and John Collier identified the receptor for the anthrax toxin, named the anthrax toxin receptor (ATR; Bradley et al., 2001). Since the ability of the anthrax toxin to cause harm is dependent upon receptor binding, targeting the anthrax receptor might provide additional therapies that could be useful even after suspected exposure to anthrax spores. In many cases, signaling downstream of cell surface receptors involves the activation of protein and lipid kinases. Successful use of the small molecule kinase inhibitor Gleevec in chronic myelogenous leukemia has shown that targeting kinases might provide an efficient means to treat various diseases. This goal of this project is to study the ATR signaling pathway in order to identify key effector molecules as targets for inhibition. The role of ATR in mediating toxin internalization will be dissected using biochemical and immunofluorescence methods in mammalian cells. The zebrafish will be used as an animal model to study ATR function in vivo and to assess its potential as an animal model for testing drugs aimed at blocking toxin action. The applicant has 3 specific aims which will be undertaken in collaboration with the Young and Collier labs. Aim 1. To investigate the role of the cytoplasmic domain of the anthrax receptor for potential therapeutic intervention. Aim 2. To determine the physiological role of the anthrax receptor by functional interference during normal embryonic development in the zebrafish. Aim 3. To examine anthrax toxicity in the zebrafish for use as an additional inexpensive model system for drug or vaccine testing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BCR-ABL KINASE ASSAYS FOR STI571 SENSITIVITY OF RESPONSE Principal Investigator & Institution: Kron, Stephen J.; Associate Professor; Molecular Genetics & Cell Biol; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2003; Project Start 17-JUL-2003; Project End 30-JUN-2004 Summary: (provided by applicant): This phased innovation award proposal is focused on developing a robust approach to quantitative assay of specific protein tyrosine kinase activities from cancer cells. Our model is the oncogenic BCR-ABL fusion protein, the gene product of the t(9;22) Philadelphia chromosome (Ph1) translocation observed in the vast majority of Chronic Myelogenous Leukemia (CML) and in up to 30% of adults with Acute Lymphoblastic Leukemia and in other hematological neoplastic diseases. The activation of Abl kinase by fusion to BCR that is inferred to underly the malignant transformation of Phl positive CML is effectively opposed by the orally administered tyrosine kinase inhibitor (TKI) Imatinib Mesylate (IM, STI-571, Gleevec). The activity of IM as an Abl kinase inhibitor in vitro is thought to be the critical determinant of its efficacy in vivo. Nonetheless, a clinically useful assay for IM inhibition of BCR-ABL kinase activity in circulating CML leukemia cells is lacking. We propose to develop a protein/peptide chip-based assay for BCR-ABL that can detect the degree of inhibition by IM to evaluate dosing and drug resistance. Insofar as other activated tyrosine kinases may be critical mediators of malignancy in both leukemias and solid tumors, developing such an assay would be a powerful tool in evaluating other TKI drug candidates targeting these kinases for their efficacy in vivo. Thus, this project is directed at two major discovery objectives and three development objectives. First, in the initial project
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year, we intend to use our established methods for anti-phosphotyrosine antibodybased detection of purified Abl kinase activity on a peptide chip to 1) Recapitulate our Abl kinase assay with undiluted whole cell extracts from cell lines expressing BCR-ABL and 2) Use this assay to measure the inhibition of BCR-ABL by IM both in extracts and intact cells. During the development phase, we intend to use both BCR-ABL expressing cancer cell lines and circulating leukemic cells from treated patients as samples to 1) Optimize the BCR-ABL substrate and reaction conditions to enhance sensitivity and specificity of phosphorylation, 2) Examine alternative detection methods for BCR-ABL activity based on phosphospecific antibodies and thiophosphate targeted chemistry, and 3) Evaluate different chemistries for immobilizing BCR-ABL substrates on a surface and geometries for detection of phosphorylation. By these aims we intend to develop a highly versatile kinase assay system which can be applied to monitoring of patient response to IM and as a tool for discovery and testing of new TKI cancer drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BCR-ABL RNA LEVELS TO MONITOR STI571 LEUKEMIA THERAPY Principal Investigator & Institution: Press, Richard D.; Pathology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 14-FEB-2003; Project End 31-JAN-2005 Summary: (provided by applicant): The recent discovery, validation, and accelerated FDA approval of the tyrosine kinase inhibitor STI571 (Gleevec) for the treatment of chronic myeloid leukemia (CML), the first such rationally-designed, small molecule cancer therapy, confirms the validity of the molecular targeting approach to cancer drugs. Aberrant CML cell growth is caused by the constitutive expression of the bcr-abl kinase, a chimeric fusion protein resulting from a leukemia-specific chromosomal translocation [t(9;22)]. STI571's targeted inhibition of this kinase activity specifically represses the leukemic clone without the typical toxicity of conventional nonspecific cancer drugs. Although >95% of chronic phase CML patients undergo a complete hematologic response to STI571, only a minority experience a complete cytogenetic response, the best current surrogate marker of long-term survival. After 18 months of daily STI571 therapy, approximately 28% of chronic phase patients lose their complete hematologic response. STI571 also induces an initial hematologic response in approximately 50-80% of CML patients with accelerated phase or blast crisis CML, but again these responses are typically only transient. This heterogeneity of responses suggests the pressing need for better laboratory methods to monitor and predict STI571 treatment efficacy to identify patients likely to have disease progression who may benefit from additional (more toxic) therapies. The considerable institutional resources in expertise and STI571-treated patient volume that have been built by co-investigator and STI571 co-developer Brian Druker represent a unique opportunity to develop and test novel laboratory methods to molecularly monitor STI571's treatment efficacy. This proposal's specific aims are then to: 1) validate a novel, quantitative, ultra-sensitive bcrabl RT-PCR assay for quantifying minimal residual disease in STI571-treated patients, 2) assess whether serial bcr-abl RNA levels in STI571-treated patients can be used to predict and/or monitor clinical disease progression, and 3) establish a storage bank of clinical samples from STI571-treated patients to enable future studies of STI571 drug resistance mechanisms. As STI571 is the first of perhaps many soon-to-come molecularly targeted cancer therapies, the successful achievement of these aims will likely serve as the model by which the efficacy of other novel therapies may be similarly monitored. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CANCER CENTER CORE SUPPORT GRANT Principal Investigator & Institution: Gasson, Judith C.; Professor of Biological Chemistry; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-DEC-1977; Project End 30-NOV-2007 Summary: This is a five-year CCSG renewal (years 29-34) for the 231-member Jonsson Comprehensive Cancer Center at UCLA. Over the past five years, there have been extensive changes, including strengthening the leadership of the Program Areas with new appointments. The Division of Basic Sciences has added the recently formed Gene Regulation Program Area, and now consists of five Program Areas: 1) Signal Transduction; 2) Molecular, Cellular & Developmental Biology; 3) Tumor Immunology;4) Viral & Chemical Carcinogenesis; and 5) Gene Regulation. The Division of Cancer Prevention & Control Research hassubstantially strengthened its two Program Areas: 1) Healthy & At-Risk Populations; and 2) Patients & Survivors. The Division of Clinical/Translational Research has added the former developmental program area, Genitourinary Oncology (formerly Prostate Oncology), and now consistsof four Program Areas: 1) Women's Cancers; 2) Hematopoietic Malignancies & Bone MarrowTransplantation;3) Genitourinary Oncology; and 4) Cancer Therapy Development (formerly Solid Tumor Oncology). New Shared Resources are proposed, including Gene Expression Core, Immunology, Tissue Array, Bioinformatics, Mass Spectrometry & Proteomics, Small Animal Imaging, and Family & Genetic Evaluation. This gives a total of 14 Shared Resources, including those continuing from the previous funding period, Flow Cytometry, Nude/SCID Mouse, Media Prep, Transgenic Mouse/Embryonic Stem Cell, Human Tissue Research Center, the BASE Unit, and the Clinical Research Unit. Significant research accomplishments over the past funding cycle include our participation in the FDA approval of Herceptin and Gleevec. Cancer focus has been strengthened considerably, as evidenced by a doubling of the ratio of NCI dollars to number of JCCC members. The number of patients enrolled on cancer therapeutic trials has increased to 5,335 over the past five years, from 3,348 during the previous funding cycle. Finally, $5,594,251 in new cancer program awards has been received during the past 18 months, including an "In Vivo Imaging Center" grant, a Director's Challenge Award, and a Lung SPORE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHARACTERIZATION OF LEIOMYOSARCOMA AND GIST BY GENOMICS Principal Investigator & Institution: Zhang, Wei; Director, Cancer Genomics Core Lab.; Neuro-Oncology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Leiomyosarcomas are a group of highly heterogeneous tumors differing in locations, pathological features, response to therapy, and propensity for metastasis. Historically, leiomyosarcomas originating from the gastrointestinal (GI) tract do not respond to conventional chemotherapy, whereas, leiomyosarcomas arising from other organ systems are more likely to respond to doxorubicin-based therapies. This observation was refined by others and it became clear that patients with (gastrointestinal stromal tumor) GIST had not only poor response rates to standard investigational therapy, but also a worse overall outcome. Recent discoveries made by basic scientists, pathologists and clinical investigators has led to an
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understanding of the biological importance of c-kit in GISTs and the development of one of the most exciting examples of targeted therapy to date. The success of the c-kit tyrosine kinase inhibitor STI-571 (Gleevec) has caught the attention of the scientific community. Understanding the mechanisms of response and resistance to STI-571 will broaden our understanding of cancer biology and lead to strategic approaches in the treatment of other malignancies. The aims of this study are to identify molecular events at the level of gene expression that are associated with prognosis, metastasis, and the dramatic responses to STI-571 that have been observed with GIST but not leiomyosarcomas arising outside of the GI tract. We will couple gene-expressionprofiling studies with high throughput confirmation and functional validation studies to gain understanding of the mechanisms underlying the important clinical phenotypes. We will test three related hypotheses. 1) There are key cellular pathway genes whose differential expressions are responsible for the different prognoses of leiomyosarcoma and GISTs; 2) There are key metastasis-regulating genes whose expressions are responsible for different metastasis potentials of leiomyosarcoma; 3) There are key genes that regulate response to STI-571 treatment in GIST but resistance to STI-571 in leiomyosarcomas arising outside the GI tract. In this proposal, we will test these 3 hypotheses with 3 specific aims taking advantage of high throughput transcriptome profiling technologies, high throughput tissue microarray and real-time polymerase chain reaction (PCR) validation, and in vitro gene perturbation functional studies. Aim 1: To generate transcriptome data using a microarray technique and to identify genes associated with extremity leiomyosarcomas (including retroperitoneal, vascular, uterine and extremity sites of origin) and GISTs. Aim 2: To identify genes that are involved in leiomyosarcoma and GIST metastasis and functionally test those genes in an in vitro invasion assay. Aim 3: To identify genes that regulate cellular response and resistance to the tyrosine kinase inhibitor STI-571, a drug for treating GISTs that have c-kit mutations and activation. Through this hypothesis-driven and discovery-driven program, we anticipate discovery of markers for clinical prediction as well as understanding of the molecular basis for those important clinical phenotypes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMICAL GENETIC PROFILING OF ENGINEERED TUMOR CELLS Principal Investigator & Institution: Stockwell, Brent R.; Fellow; Whitehead Institute for Biomedical Res Biomedical Research Cambridge, Ma 02142 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2006 Summary: (provided by applicant): The central hypothesis underlying this research project is that molecular mechanisms exist for killing tumor cells selectively and that these mechanisms can be elucidated through the use of chemical genetic screens. In this chemical genetic approach, a high-throughput screen is used to select drugs that exert a desired phenotypic effect in a cellular assay. Subsequently, the molecular mechanisms by which these drugs exert their effects are determined. The primary technological barrier to widespread use of the chemical genetic approach is the difficulty of identifying the molecular basis of action of new drugs of unknown function. New strategies that allow for rapid identification of the molecular mechanism by which drugs exert their effects are of great value. This research project will result in the development of such a method and will result in the identification of molecular mechanisms that enable selective killing of engineered tumor cells. This project will result in the assembly and annotation of a chemical library of 5,000 drugs of known function using manual and automated Literature searching. These drugs will be tested for their ability to kill genetically defined tumor cells but not primary cell precursors to these tumor cells.
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Some of these tumor-selective killing agents will act by known molecular mechanisms and others will act by new, previously uncharacterized mechanisms. Using a variety of computational methods (neural networks, multiple linear regression, decision trees, self organizing maps, and genetic algorithms), we will demonstrate that functional annotation of chemical libraries makes it possible to identify specific molecular mechanisms that underlie cellular phenotypes, such as selective, apoptotic death in engineered tumor cells. The recent discovery of Gleevec (STI-571), a BCR-ABL kinase inhibitor that selectively kills BCR-ABL transformed cells, illustrates the clinical value of tumor-selective cytotoxic agents. New compounds that selectively kill tumor cells may be candidates for development as anticancer drugs or they may serve to illuminate novel drug targets for anticancer drug development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--IMMUNOLOGY Principal Investigator & Institution: Wieder, Eric D.; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 28-FEB-2008 Summary: The Immunology Core will provide assays of cellular immunity in support of this Program Project. The assays provided by the core will include the quantitation, immunophenotyping, and functional analyses of antigen-specific CD8+ cytotoxic T lymphocytes (CTL) and CD4+ T helper cells. It will be important to have consistent measures of both the quantity and quality of the antigen-specific T cells so that the projects supported by this core modulating the immune response to CML will have useful immunology data to correlate with the measured clinical response(s). These measurements of immune status will be made on treated patients, some of which will be immuno-compromised, in the context of stem cell transplant patients both in the allogeneic and autologous setting (Project:Champlin), and in patients with Gleevec resistance (Project:Cortes). This core will also support the development of the methodology for the expansion and purification of PRl-specific CTL (Project:Molldrem), and the verification of immune function in transduced suicide T cells (Project:Kornblau). It will also be important to consider functional specific immunity in the context of how each patient's overall immune status and recovery is progressing. Therefore, in addition to monitoring CML-specific CTL, we will assay viral-specific T cells, examine the overall quantity and phenotype of the entire CD4 and CD8 T cell populations, and assess overall thymic function and T cell receptor (TCR) diversity. Specifically, the core will provide the following immune assays: 1) Assess the numbers and function of leukemiaspecific T cells in patients with CML before and after immunotherapeutic interventions; 2) Assess the numbers and function of T cells specific for viral antigens important in infection prophylaxis in CML patients; 3) Systematically examine the impact of therapy for CML on the immunophenotypic composition of the naive and memory T cell repertoire; 4) Examine the role of thymic function on leukemia and viral specific T cells after stem cell transplant (SCT). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EPIGENETIC ALTERATIONS IN CHRONIC MYELONGENOUS LEUKEMIA Principal Investigator & Institution: Feinberg, Andrew P.; Professor; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 28-FEB-2008
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Summary: The purpose of this project is to investigate epigenetic alterations in CML. We have previously discovered imprinted genes in humans and loss of imprinting (LOI) in cancer. Genomic imprinting is a chromosomal modification in the gamete or zygote leading to differential expression of the two parental alleles of a gene in somatic cells of the offspring. LOI can lead to the expression of the normally silent copy of growthpromoting genes in cancer, and to loss of expression of the normally transcribed copy of growth inhibitory genes. In addition, we have found alterations in DNA methylation, a covalent modification of the nucleotide cytosine, that are specific for tumor cells with LOI. As part of this program project, we have previously discovered LOI in CML, which appears to be specific for progression to accelerated phase and blast crisis. In the current grant period, we have identified specific alterations in methylation of the IGF2 gene that are linked to LOI and are found in circulating leukemic cells of patients with accelerated phase or blast crisis, as well as in the year preceding disease progression. This methylation alteration appears to be specific for leukemic cells, as it is not found in normal circulating myelocytes or marrow progenitor cells. We will now determine whether clinical subtype and response to therapy can be classified by altered methylation of IGF2, and/or by alterations in the epigenotype of a group of genes analyzed by high throughput bisulfite methylation analysis, as well as array-based methylation analysis. These efforts will be used to generate an "epigenetic profile" of CML that can be used for classification and evaluation of therapeutic response as well as therapeutic planning. We will also determine the relationship between clinical subtype or the response to therapy, and histone modifications, as well as the expression of the chromatin modifying genes responsible for these changes. These latter studies will be focused on identifying chromatin factors responsible for Gleevec resistance, as well as for epigenetic silencing of the wild type bcr allele in disease progression, and they will be performed in collaboration with Dr. Talpaz and Dr. Arlinghaus. These experiments will provide direct insight into the pathogenesis of CML progression and help to identify novel targets in the therapy of CML. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FLAVOPIRIDOL AND IMATINIB IN BCR/ABL+ LEUKEMIA Principal Investigator & Institution: Grant, Steven; Professor; Internal Medicine; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2003; Project Start 11-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Recent evidence suggests that neoplastic cells are particularly susceptible to a strategy involving simultaneous interruption of survivalassociated signal transduction and cell cycle regulatory pathways. Consistent with this notion, we have observed in preclinical studies that the cyclin-dependent kinase inhibitor flavopiridol (NSC 649890) interacts synergistically with the Bcr/Abl kinase inhibitor imatinib (STI571; Gleevec) to induce mitochondrial injury, caspase activation and apoptosis in Bcr/Abl+ human leukemia cells, including those highly resistant to imatinib. These events are associated with multiple perturbations in survival signaling and cell cycle-related pathways, including down-regulation of Mcl-1 and Bcl-xL, reduced expression of cyclin D1, activation of JNK, and inactivation of CREB and Stat5. Based upon these findings, a multi-institutional Phase I trial has been developed in which patients with progressive CML (chronic and accelerated phase) or CML-BC or Philadelphia chromosome+ AML or ALL will be treated with escalating doses of daily imatinib in conjunction with flavopiridol administered as a 1-hr infusion weekly x 3 q month. The goals of this Phase I trial are to define the MTD for these agents, characterize dose-limiting toxicities, and gain preliminary information regarding activity of the
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regimen. Correlative laboratory studies will test the hypothesis that in vivo administration of imatinib in conjunction with flavopiridol will induce perturbations in apoptotic regulatory proteins in peripheral blood Bcr/Abl+ cells (e.g., diminished expression of Mcl-1, Bcl-xL, and cyclin D1, inactivation of Stat5 and CREB, activation of JNK) similar to those observed in Bcr/Abl+ cell lines exposed to these agents in vitro. Other studies will investigate a) effects of the imatinib/flavopiridol regimen on Stat5 phosphorylation of Bcr/Abl+ peripheral blood cells by flow cytometry; b) the pharmacokinetics of imatinib and flavopiridol when administered together; and c) the presence of Bcr/Abl mutations as well as increased Bcr/Abl expression/activity in cells from imatinib-resistant patients, and their possible relationship to imatinib/flavopiridol pharmacodynamics. Information derived from this trial will provide a foundation for a successor Phase II trial and correlative laboratory studies which will address issues of regimen activity and imatinib/flavopiridol molecular interactions more definitively. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LEUKEMIAS
GLEEVEC
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Principal Investigator & Institution: Bhalla, Kapil N.; Professor of Medicine; Moffitt Cancer Center; University of South Florida 4202 E Fowler Ave Tampa, Fl 33620 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (PROVIDED BY APPLICANT): Constitutively active Bcr-Abl tyrosine kinase (TK) promotes cell growth and inhibits apoptosis in Bcr-Abl positive acute leukemia cells by activating a variety of downstream molecular mechanisms. Gleevec (previously known as CGP57148B or STI-571) is a relatively specific Bcr-Abl TK inhibitor which is highly active in CML. Recent studies from our laboratory have shown that at clinically achievable concentrations of 0.25 to 1.0 uM, Gleevec induces differentiation and apoptosis and sensitizes Bcr-Abl positive cultured human acute leukemia HL-60/BcrAbl and K562 cells to antileukemic drugs and Apo-2L/TRAIL. Gleevec inhibits tyrosine phosphorylation of Bcr-Abl, as well as downstream of Akt kinase and STAT5. This results in the inhibition of STAT5 and NFKB activities and lowering of the levels and activities of the antiapoptotic Bcl-xL and IAP (inhibitors of apoptosis) proteins. However, these studies need to be extended to patient-derived, CD34+ CML-blast crisis (BC) and Bcr-Abl positive ALL progenitor cells. Although Gleevec also has significant clinical activity in CML-BC and Bcr-Abl positive ALL, the complete response rates have been low and duration of most remissions short. To study the intracellular mechanism of Gleevec-resistance, we have isolated HL-60/Bcr-Abl and K562 cells that are capable of growth in the continuous presence of clinically relevant levels of Gleevec. Notably, these cells are sensitive to novel anti-Bcr-Abl targeted agents 17-allyl-amino geldanamycin (17-AAG) or PD 180970. However, the mechanisms of resistance and the activities of these novel agents that may overcome Gleevec-resistance in CD34+ CMLblast crisis (BC) and Bcr-Abl positive ALL progenitor cells need to be determined. Therefore the specific aims of this proposal are: AIM 1: To determine the molecular mechanisms underlying the antiapoptotic activity and chemoresistance due to Bcr-Abl and its inhibition by Gleevec in patient-derived, Bcr-Abl positive leukemic blast progenitor cells. AIM 2: To determine the growth inhibitory and apoptotic effects of combinations of Gleevec with novel agents, e.g., Apo-2L/TRAIL, PD180970 or 17-AAG against Bcr-Abl positive leukemic blast versus normal progenitor cells. AIM 3: To determine the Bcr-Abl based mechanisms of Gleevec-resistance in leukemic blast progenitors from patients with Gleevec-refractory CML-BC or Bcr-Abl positive adult ALL. AIM 4: To determine the in vitro cytotoxic effect, and its underlying mechanisms,
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of 17-AAG or PD180970 against Gleevec-resistant leukemic blast progenitor cells. These in vitro studies may help define novel therapeutic strategies for clinical testing against Bcr-Abl positive acute leukemias. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPROVING MOLECULAR RESPONSES USING IMATINIB MEYSLATE Principal Investigator & Institution: Cortes, Jorge; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 28-FEB-2008 Summary: The principal objectives of this project are to identify improved therapeutic options for patients with CML. Imatinib mesylate (Gleevec, STI571) has significant activity in CML, but with standard-dose imatinib few patients have achieved a molecular remission. Thus the potential for cure with imatinib alone is questionable. The first aim is to determine whether pegylated interferon and GM-CSF in combination with high-dose imatinib may improve the molecular responses to high-dose imatinib alone. Patients with newly diagnosed CML will be treated with high-dose imatinib. After 6 months, they will be randomized to continue imatinib alone or in combination with PEG-IFN and GM-CSF. The goal is to improve the rate of molecular remissions at 12 months. The second aim of this project is to evaluate the significance of these molecular remissions. Patients will be monitored with competitive or real-time PCR during therapy. The objective is to determine whether complete molecular remission translate in long-term disease free survival. In addition, we will investigate whether the ratio of Bcr/Abl to Abl can be used to predict probabilyt of relapse, whether low levels below a certain threshold will identify a low probability of relapse and whether these could help determine duration of therapy, and whether increasing levels correlate with relapse and can thus be used to change treatment strategies. The third aim is to investigate whether immunotherapy, in the form of PR1 vaccine, can improve the responses in patients who are refractory to imatinib. Because PR1 is presented in an HLA-A2-restrivcted fashion, patients with this phenotype will be randomized to receive PR1 and imatinib, with or without interferon. The fourth aim is to investigate new agents for the treatment of CML refractory to imatinib. The first agent to be investigated is the proteasome inhibitor PS341 or bortezomib. Patients will be treated with PS-341 twice weekly for 2 weeks every 3 weeks. Besides the clinical efficacy, the induction of apoptosis and the effect on CML cell cultures will be determined. This drug could eventually be combined with imatinib. Other new agents would eventually be used in this setting in subsequent years of this proposal. The long-term goal of this project is to improve the treatment of CML with the objective of achieving cures outside of the bone marrow transplant setting in a significant number of patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MESENCHYMAL STEM CELLS AS DRUG DELIVERY VEHICLES IN CML Principal Investigator & Institution: Andreeff, Michael W.; Stringer Professor for Cancer Treatment; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 28-FEB-2008 Summary: Chronic myelogenous leukemia (CML) is a clonal disorder arising from the neoplastic transformation of hematopoietic stem cells. Bcr/Abl, the gene product of the characteristic (9;22) translocation (Philadelphia chromosome) functions as constitutive
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tyrosine kinase. Recently, the tyrosine kinase inhibitor Gleevec (Imatinib, STI571) was introduced as effective therapy for suppression of CML. While STI571 induces a high rate of complete hematological and cytogenetic remissions, residual leukemic cells are readily detected in the majority of patients and development of resistance to STI571 has been reported. Systemically administered interferon-alpha (INFalpha) had been the treatment of choice for CML prior to STI571. However, due to its short half-life, very high doses were required for therapeutic responses associated with undesirable systemic side effects. Clinical trials are ongoing combining both treatment modalities, STI571 and INFalpha. We hypothesized that the production of INFalpha and other biologically active proteins, by bone marrow resident cells might exert biological activity while decreasing systemic side effects. Mesenchymal stem cells (MSC) are nonhematopoietic cells residing in the bone marrow that can be isolated, expanded ex vivo, and transplanted. They "home back" to their site of origin, the bone marrow. We have extensive evidence that i.v. injected MSC contribute and proliferate in the marrow and also in the stroma of solid tumors and their metastases. We here propose to use MSC to produce regulated therapeutic genes in situ, including INFalpha, MDA7/CD24 and MRP2. Philadelphia chromosome (Ph')-negative MSC from both normal and CML donors were expanded ex vivo, and infected with an adeno-associated virus (AAV) expressing either CMV-driven INFalpha or progesterone regulated INFalpha. We compared this MSC-produced INFalpha with pharmacy grade INFalpha in vitro and in vivo. Both INFalpha's appeared identical in their ability to inhibit human Ph'-positive leukemias in vitro, but in the KBM5 model of CML blast crisis systemically injected IFNalpha was ineffective in vivo, whereas IFNalpha-MSC exerted significant anti-tumor effects and doubled the survival of tumor bearing animals. Exposure to INFalpha-MSC resulted in upregulation of MHC Class 1 antigens on CML patient cells. We are proposing to extend our preliminary in vitro and in vivo studies with the aim of developing a clinical trial of INFalpha-MSC in CML patients resistant to STI571 in chronic, accelerated and blast phases of CML, and relapsing after BMT. Furthermore, we propose to explore MSC-produced human melanoma differentiation-associated gene 7 (MDA7/IL24), a novel cancer growth suppressing and apoptosis-inducing member of the IL-10 family of cytokines, for the treatment of CML. MDA7 possesses Th1 cytokine activity and induces apoptosis in 60 tested cancers, but not in normal cells, independent of p53 status, but not in normal cells. It also exerts strong anti-angiogenic effects. We have evidence that MDA7-MSC inhibit preferentially the growth of STI571-resistant CML cells. Alternatively, we will investigate effects of MSC-produced MRP2, a MIP1 alpha-related protein, which is induced in CML by STI571. In conclusion, we propose to develop MSC as a platform for the in situ production of therapeutic proteins in CML. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR ONCOGENESIS OF BCR-ABL--SECRETED CELL DEATH FACTORS FOR BCR IN LEUKEMIA Principal Investigator & Institution: Arlinghaus, Ralph B.; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 28-FEB-2008 Summary: This grant application concerns two topics. The first concerns the role of secreted cell death factors in Bcr-Abl positive chronic myelogenous leukemia (CML). We will primarily focus on 24p3, a lipocalin that is secreted by IL-3 deprived mouse 32D cells, and was demonstrated by another group to cause cell death in many types of hematopoietic cells. Lipocalins are a large family of secreted proteins that function as ligand-binding molecules with a variety of biological activities. We found that Bcr-Abl
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positive mouse 32D cells express high level of 24p3 transcripts in the absence or presence of IL-3. Conditioned medium from Bcr-Abl positive 32D cells induces cell death in normal mouse marrow cells but not in Bcr-Abl positive cells. We hypothesize that Bcr-Abl induced leukemia results from two separate effects: 1) the oncogenic immortalization of leukemia cells; and 2) the induction of cell death factors that destroy normal blood cells, leading to immuno-suppression and other effects that affect normal blood cell function. We plan to characterize the 24p3 protein secreted by Bcr-Abl and investigate the mechanisms of 24p3 induction and the resistance of Bcr-Abl cells to 24p3mediated cell death. We also plan to determine the effects of reduced levels of 24p3 secretion on the induction of leukemia in mouse models using lentivirus mediated transduction of anti-sense 24p3. The second topic concerns the inhibitory role of Bcr directed towards Bcr-Abl positive cells and, particularly, in cells resistant to Gleevec (STI-571). We will search for more potent forms of the Bcr inhibitory structure and study the mechanism of action. We have developed an efficient lentivirus gene transduction system, which is very useful for gene transduction in hematopietic cells. We will transduce cells with the replication-defective BCR encoding lentivirus equipped with a bi-cistronic message, which allows expression of BCR and a GFP reporter gene. Both in vitro cell systems and mouse models for CML will be tested with the BCR lentivirus to determine the effects of BCR expression in this leukemia. Based on our published papers, we propose a hypothesis that endogenous Bcr down-regulates the Bcr-Abl oncoprotein and thus reduction of Bcr protein levels will enhance the intrinsic oncogenic activity of the Bcr-Abl oncoprotein. We will test this hypothesis by expressing 3' antisense BCR sequences and the ABL SH2 domain sequence in Bcr-Abl positive cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RESISTANCE OF CML STEM CELLS TO STI571 (GLEEVEC) Principal Investigator & Institution: Bhatia, Ravi; City of Hope/Beckman Research Institute Helford Building Duarte, Ca 910103000 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Chronic myelogenous leukemia (CML) results from malignant transformation of a hematopoietic stem cell. Malignant cells in CML are characterized by the t (9; 22) translocation resulting in the BCR/ABL gene rearrangement. The BCR/ABL protein has constitutively activated protein-tyrosine kinase activity, which is essential for transformation in CML. STI571 (STI, Gleevec), an inhibitor of the BCR/ABL tyrosine kinase, has shown a high degree of activity in all stages of CML in early clinical studies. However, a significant proportion of patients treated with STI do not achieve cytogenetic responses. Moreover, for patients who achieve cytogenetic responses following STI therapy, it is not known whether responses to STI will be durable and result in prolongation of survival. Our preliminary studies indicate that persistent BCR/ABL positive progenitor cells can be detected even in responsive patients in complete cytogenetic remission, indicating that they may be at risk for relapse. We hypothesize that lack of cytogenetic response to STI treatment will correlate with in vitro observations of reduced inhibition of leukemic progenitor growth and reduced suppression of BCR/ABL activated signaling mechanisms by STI. We further hypothesize that the burden of persistent malignant progenitors in patients in cytogenetic response following STI treatment will predict for durability of response. We will determine the relationship between cytogenetic response or lack of response to STI treatment and laboratory assessments of STI-induced inhibition of leukemic progenitor growth and BCR/ABL signaling activities (Specific Aim 1). Development of predictors of non-responsiveness may allow upfront identification of patients requiring alternative
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treatment approaches. We will also determine the relationship between persistent malignant progenitors in patients with cytogenetic responses to STI and durability of response and risk of relapse, and investigate mechanisms underlying persistence of malignant progenitors (Specific Aim 2). These studies will determine the efficacy of STI in targeting malignant primitive hematopoietic progenitors and may lead to the development of surrogate markers for long-term response. The long-term goal of these studies is to allow optimal use of STI, alone or in combination, in the treatment of CML and improve overall outcomes of treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SMALL MOLECULE KINASE INHIBITOR FOR MALIGNANT GLIOMA Principal Investigator & Institution: Stiles, Charles D.; Professor; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 10-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Fundamental insights into the molecular action of oncogenes and tumor suppressor genes are being translated into a new generation of anti-cancer drugs that target specific cell signaling pathways. We hypothesize that the genetic background of malignant gliomas will dictate (and ultimately predict) the response to these signal transduction inhibitors. The broad objective of this project is to test this hypothesis by exploiting an important opportunity. Our group is involved in the initial clinical trial with a signal transduction inhibitor, the platelet-derived growth factor receptor (PDGFR)/abl blocker STI571 (Gleevec), in gliomas. We have access to clinical samples from this trial and we are in position to correlate genetic data with clinical responses. The project has two specific aims: Specific Aim 1 is to determine whether clinical responses to Gleevec correlate with any of the major stereotypical and well-characterized genetic cohorts of glioma: 1) EGF receptor (EGFR) gene amplification, 2) p53 loss-of-function mutation, 3) loss-of-function PTEN mutations and 4) p16/CDKN2A deletion. In addition, we will examine the sequence of the PDGFR kinase domain for potential mutations that may associate with drug refractoriness. Specific Aim 1 insures that a new generation of "smart drugs" is given a fair opportunity to succeed. Even if this drug fails clinical trials, it will be important to know that it was tested on a representative number of gliomas from each of the major genetic cohorts. Specific Aim 2 is to screen for novel, unanticipated genetic lesions that may correlate with response to Gleevec. Specific Aim 2 addresses a potential pitfall with the first specific aim: What if the drugs prove to be effective on a subset of patients - but that subset does not correspond to any of the stereotypical genetic cohorts? Single nucleotide polymorphism (SNP) arrays will be used to screen for novel lesions because, in most cases, the tumor samples for this project will be available as archival tissue only. SNP array analysis will not only provide an independent test of the hypothesis that the genetic background of a glioma determines the response to signal transduction inhibitors, but it may also identify useful new prognostic indicators for these tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SRC FAMILY TYROSINE KINASES IN TUMOR CELL SIGNALING Principal Investigator & Institution: Smithgall, Thomas E.; Associate Professor; Molecular Genetics & Biochem; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-JUN-2008
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Summary: (provided by applicant): Bcr-Abl is the oncogenic tyrosine kinase expressed as a result of the Philadelphia translocation in chronic myelogenous leukemia (CML). Src family kinase inhibitors and dominant-negative mutants block Bcr- Abl-induced transformation of myeloid progenitor cells, strongly suggesting that Bcr-Abl cooperates with Src in CML pathogenesis. Experiments proposed here will investigate the molecular mechanisms that regulate the interaction of Bcr-Abl with Src kinases, determine whether Src kinases affect Bcr-Abl kinase activity and sensitivity to the antiCML drug STI-571 (Gleevec), and look at the genetic requirement for Src kinases in a model system for CML: Aim 1: Test the hypothesis that association with Bcr-Abl is sufficient to induce Src kinase activation. Recent data from our laboratory show that interaction with Bcr-Abl involves Src family kinase SH2 and SH3 domains, suggesting that association with Bcr-Abl may be sufficient to induce sustained Src kinase activation in vivo. Using fibroblast and myeloid cell transformation assays, we will test this idea by co-expressing Hck and Lyn with regions of Bcr-Abl previously shown to bind to these myeloid Src family members in vitro. Identification of the Bcr-Abl regions essential for Src family kinase activation will define a novel molecular surface for anti-CML drug design. Aim 2: Test the hypothesis that Src kinases phosphorylate Bcr-Abl in vivo and modulate its kinase activity and sensitivity to inhibition by STI-571. Preliminary data show that Src kinases directly phosphorylate the c-Abl kinase domain on the activation loop tyrosine in vitro. Bcr-Abl mutants lacking Src family kinase phosphorylation sites and selective inhibitors will be used to determine whether Src family kinases affect BcrAbl activity and sensitivity to STI-571, which selectively inhibits the inactive conformer of Abl. Aim 3: Test the genetic requirement for Src family kinases in Bcr-Abl signal transduction and STI-571 sensitivity. The transforming activity of Bcr-Abl will be assessed in hematopoietic colony-forming assays of bone marrow cells from mice lacking the three major myeloid Src family members (Hck/Lyn/Fgr), all of which interact with Bcr-Abl. Triple-knockout cells will also be used to address the requirement for Src family members in coupling Bcr-Abl to Stats and other downstream effectors as well as sensitivity to STI-571. Successful completion of these studies will provide strong validation of myeloid-specific Src kinases as targets for second-generation anti-CML drug development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TK-BASED METHODS TO IMPROVE RADIOIMMUNOTHERAPY Principal Investigator & Institution: Baranowska-Kortylewicz, Janina; Radiation Oncology; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2004; Project Start 01-MAR-2004; Project End 28-FEB-2007 Summary: (provided by applicant): The primary objective of this research is the development of methods to improve radioimmunotherapy (RIT) of pancreatic cancer (PanC). PanC is the fourth leading cause of cancer death in men and women in the USA. RIT has potential of becoming a valuable tool in the treatment of PanC. Impressive responses to RIT have already been observed in lymphoma. By contrast, with rare exceptions, solid tumors have proven resistant thus far to RIT. Poor responses are rooted primadly in the physiology of solid tumors. Penetration of RIT is not homogeneous and only a minute fraction of injected doses reaches tumor. Poor blood supply, tight junctions between epithelial tumor cells and the large tumor stroma component typical of PanC create a formidable physical barrier to the RIT diffusion into the tumor mass. Two methods of improving RIT of PanC proposed in these studies deal with difficulties unique to pancreatic cancer: large tumor stroma and poor vascular permeability. The first approach is based on a previously unrecognized therapeutic potential of inhibition
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of the platelet derived growth factor receptor PDGFr-beta ST1571) in tumor stroma cells. The control of interstitial fluid pressure (IFP) is one of the known biological functions of PDGF-BB. PDGFr-beta are expressed in the stromal compartment of PanC, inhibitors of PDGFr-beta will improve RIT by reducing tumor IFP thereby increasing the uptake of radioimmunoconjugates, and consequently augmenting tumor responses to RIT. To achieve this objective a highly selective antagonist of PDGFr-beta STI571 (Gleevec) will be included in the RIT scheme to reduce tumor IFP and to increase the uptake of RIT in tumor. Preliminary studies indicate that tumor responses to RIT augmented with STI571 are improved by as much as 200%. There also appears to be a tumor-dependent response to the antagonist alone, i.e., a remarkable tumor growth delay is observed in response to STI571 in a mouse pancreatic adenocarcinoma model. Further improvements in the delivery of RIT are anticipated by the inclusion of agents that increase the vascular permeability (VP) of tumor blood vessels. The transport of RIT into tumors relies on VP of tumor vessels to macromolecules. Response- including levels of hypoxia, interstitial fluid pressure, changes in vasculature, proliferative and apoptotic fractions, and changes in tumor's radiosensitivity will be evaluated. This knowledge will ultimately lead selective conformationally biased agonist pepUdes (C5aAP) derived from the Cterminal domain of the human C5a complement substantially improve the outcome of RIT. Combination of both approaches are certain to bdng further improvements. Studies proposed here will define the role of these adjuvants in RIT of PanC and the mechanism of their action. Radiolabeled antibodies B72.3 and CC49 that recognize tumorassociated antigen TAG-72 will be evaluated in mouse models of PanC. Parameters such as the radioisotope uptake, tumor responses to augmented RIT, changes in tumor physiology, to improved clinical radioimmunotherapy of pancreatic cancer. 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 “Gleevec” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for Gleevec in the PubMed Central database: •
Effects of STI571 (gleevec) on pancreatic cancer cell growth. by Li J, Kleeff J, Guo J, Fischer L, Giese N, Buchler MW, Friess H.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=212230
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Gleevec (STI-571) inhibits lung cancer cell growth (A549) and potentiates the cisplatin effect in vitro. by Zhang P, Gao WY, Turner S, Ducatman BS.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149413
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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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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 Gleevec, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Gleevec” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for Gleevec (hyperlinks lead to article summaries): •
18FDG-Positron emission tomography for the early prediction of response in advanced soft tissue sarcoma treated with imatinib mesylate (Glivec). Author(s): Stroobants S, Goeminne J, Seegers M, Dimitrijevic S, Dupont P, Nuyts J, Martens M, van den Borne B, Cole P, Sciot R, Dumez H, Silberman S, Mortelmans L, van Oosterom A. Source: European Journal of Cancer (Oxford, England : 1990). 2003 September; 39(14): 2012-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957455&dopt=Abstract
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A novel t(6;7)(p24;q21) in a chronic myelocytic leukemia in complete cytogenetic remission after therapy with imatinib mesylate. Author(s): Gozzetti A, Tozzuoli D, Crupi R, Fanelli A, Gentili S, Bocchia M, Mazzotta S, Raspadori D, Lauria F. Source: Cancer Genetics and Cytogenetics. 2004 January 15; 148(2): 152-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14734229&dopt=Abstract
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Acceleration of tumor growth and peri-tumoral blood clotting by imatinib mesylate (Gleevec). Author(s): Samoszuk M, Corwin MA. Source: International Journal of Cancer. Journal International Du Cancer. 2003 September 20; 106(5): 647-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866022&dopt=Abstract
6 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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Activity of the Bcr-Abl kinase inhibitor PD180970 against clinically relevant Bcr-Abl isoforms that cause resistance to imatinib mesylate (Gleevec, STI571). Author(s): La Rosee P, Corbin AS, Stoffregen EP, Deininger MW, Druker BJ. Source: Cancer Research. 2002 December 15; 62(24): 7149-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499247&dopt=Abstract
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Acute renal failure secondary to imatinib mesylate treatment in chronic myeloid leukemia. Author(s): Pou M, Saval N, Vera M, Saurina A, Sole M, Cervantes F, Botey A. Source: Leukemia & Lymphoma. 2003 July; 44(7): 1239-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916879&dopt=Abstract
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Advanced gastrointestinal stromal tumors successfully treated with imatinib mesylate: a report of two cases. Author(s): Hasan S, Hassan M, Oke L, Dinh K, Onojobi G, Lombardo F, Dawkins F, Jack M. Source: Journal of the National Medical Association. 2003 December; 95(12): 1208-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14717479&dopt=Abstract
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Analysis of the impact of imatinib mesylate therapy on the prognosis of patients with Philadelphia chromosome-positive chronic myelogenous leukemia treated with interferon-alpha regimens for early chronic phase. Author(s): Kantarjian H, O'Brien S, Cortes J, Shan J, Giles F, Garcia-Manero G, Verstovsek S, Faderl S, Rios MB, Talpaz M. Source: Cancer. 2003 October 1; 98(7): 1430-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14508830&dopt=Abstract
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Case 3. Resection of originally inoperable liver metastases of gastrointestinal stromal tumor after imatinib mesylate therapy. Author(s): Lang I, Hitre E, Horvath Z, Godeny M. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 September 15; 21(18): 3538-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972533&dopt=Abstract
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Challenging problems in advanced malignancy: Case 3. Imatinib mesylate-induced interstitial pneumonitis. Author(s): Rosado MF, Donna E, Ahn YS. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 August 15; 21(16): 3171-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915610&dopt=Abstract
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Changes and challenges--the world post-Gleevec (Glivec). Author(s): Hickman JA, Lazo JS. Source: Current Opinion in Pharmacology. 2002 August; 2(4): 357-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127866&dopt=Abstract
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Chromosomal abnormalities in Philadelphia chromosome-negative metaphases appearing during imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase. Author(s): Medina J, Kantarjian H, Talpaz M, O'Brien S, Garcia-Manero G, Giles F, Rios MB, Hayes K, Cortes J. Source: Cancer. 2003 November 1; 98(9): 1905-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14584073&dopt=Abstract
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Chronic myelogenous leukemia in T cell lymphoid blastic phase achieving durable complete cytogenetic and molecular remission with imatinib mesylate (STI571; Gleevec) therapy. Author(s): Atallah E, Talpaz M, O'brien S, Rios MB, Guo JQ, Arlinghaus R, FernandesReese S, Kantarjian H. Source: Cancer. 2002 June 1; 94(11): 2996-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115389&dopt=Abstract
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Chronic myeloid leukemia following therapy with imatinib mesylate (Gleevec). Bone marrow histopathology and correlation with genetic status. Author(s): Frater JL, Tallman MS, Variakojis D, Druker BJ, Resta D, Riley MB, Hrisinko MA, Peterson LC. Source: American Journal of Clinical Pathology. 2003 June; 119(6): 833-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12817431&dopt=Abstract
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Clonal chromosome aberrations in Philadelphia-negative cells from chronic myelocytic leukemia patients treated with imatinib mesylate: report of two cases. Author(s): Herens C, Baron F, Croisiau C, Tassin F, Bours V. Source: Cancer Genetics and Cytogenetics. 2003 November; 147(1): 78-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14580776&dopt=Abstract
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Clonal evolution and lack of cytogenetic response are adverse prognostic factors for hematologic relapse of chronic phase CML patients treated with imatinib mesylate. Author(s): O'Dwyer ME, Mauro MJ, Blasdel C, Farnsworth M, Kurilik G, Hsieh YC, Mori M, Druker BJ. Source: Blood. 2004 January 15; 103(2): 451-5. Epub 2003 September 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512312&dopt=Abstract
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Comparative gene expression profile of chronic myeloid leukemia cells innately resistant to imatinib mesylate. Author(s): Tipping AJ, Deininger MW, Goldman JM, Melo JV. Source: Experimental Hematology. 2003 November; 31(11): 1073-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14585372&dopt=Abstract
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Concomitant myelodysplastic syndrome and chronic myeloid leukaemia: treatment outcomes with imatinib mesylate. Author(s): Mesa RA, Steensma DP, Hoyer J, Ketterling RP. Source: British Journal of Haematology. 2003 October; 123(2): 366-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14531922&dopt=Abstract
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Current results on the use of imatinib mesylate in patients with relapsed Philadelphia chromosome positive leukemia after allogeneic or syngeneic hematopoietic stem cell transplantation. Author(s): Ullmann AJ, Hess G, Kolbe K, Friedrich-Freksa A, Meyer RG, Gschaidmeier H, Huber C, Fischer T. Source: The Keio Journal of Medicine. 2003 September; 52(3): 182-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14529151&dopt=Abstract
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Cystic changes in hepatic and peritoneal metastases from gastrointestinal stromal tumors treated with Gleevec. Author(s): Bechtold RE, Chen MY, Stanton CA, Savage PD, Levine EA. Source: Abdominal Imaging. 2003 November-December; 28(6): 808-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14753595&dopt=Abstract
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Cystic changes in hepatic metastases from gastrointestinal stromal tumors (GISTs) treated with Gleevec (imatinib mesylate). Author(s): Chen MY, Bechtold RE, Savage PD. Source: Ajr. American Journal of Roentgenology. 2002 October; 179(4): 1059-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239065&dopt=Abstract
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Determination of drug synergism between the tyrosine kinase inhibitors NSC 680410 (adaphostin) and/or STI571 (imatinib mesylate, Gleevec) with cytotoxic drugs against human leukemia cell lines. Author(s): Avramis IA, Laug WE, Sausville EA, Avramis VI. Source: Cancer Chemotherapy and Pharmacology. 2003 October; 52(4): 307-18. Epub 2003 June 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12827297&dopt=Abstract
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Direct and fast capillary zone electrophoretic method for the determination of Gleevec and its main metabolite in human urine. Author(s): Rodriguez Flores J, Berzas JJ, Castaneda G, Rodriguez N. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2003 September 5; 794(2): 381-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12954390&dopt=Abstract
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Disseminated erythematous and pityriasiform plaques caused by imatinib mesylate. Author(s): Pasmatzi E, Monastirli A, Matsouka P, Tsambaos D. Source: Acta Dermato-Venereologica. 2003; 83(5): 391-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14609118&dopt=Abstract
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Durable molecular response to imatinib mesylate following nonmyeloablative allogeneic stem-cell transplantation for persisting myeloid blast crisis in chronic myeloid leukemia. Author(s): Staber PB, Brezinschek R, Linkesch W, Sill H, Neumeister P. Source: Haematologica. 2003 August; 88(8): Ecr29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12935988&dopt=Abstract
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EBV-positive cutaneous B-cell lymphoproliferative disease after imatinib mesylate. Author(s): Bekkenk MW, Vermeer MH, Meijer CJ, Jansen PM, Middeldorp JM, Stevens SJ, Willemze R. Source: Blood. 2003 December 1; 102(12): 4243. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14623772&dopt=Abstract
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Effect of imatinib mesylate (Gleevec) on anaplastic thyroid carcinoma cell lines. Author(s): Mitsiades CS, Sykoutri D, McMullan C, Poulaki V, Mitsiades N. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 October; 88(10): 5043-4; Author Reply 5044. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557495&dopt=Abstract
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Effect of imatinib mesylate on neuroblastoma tumorigenesis and vascular endothelial growth factor expression. Author(s): Beppu K, Jaboine J, Merchant MS, Mackall CL, Thiele CJ. Source: Journal of the National Cancer Institute. 2004 January 7; 96(1): 46-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14709738&dopt=Abstract
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Effect of rifampicin on the pharmacokinetics of imatinib mesylate (Gleevec, STI571) in healthy subjects. Author(s): Bolton AE, Peng B, Hubert M, Krebs-Brown A, Capdeville R, Keller U, Seiberling M. Source: Cancer Chemotherapy and Pharmacology. 2004 February; 53(2): 102-6. Epub 2003 November 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14605865&dopt=Abstract
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Effective treatment of hypereosinophilic syndrome with imatinib mesylate. Author(s): Salem Z, Zalloua PA, Chehal A, Bitar N, Abboud M, Kadri A, Chami B, Bazarbachi A. Source: The Hematology Journal : the Official Journal of the European Haematology Association / Eha. 2003; 4(6): 410-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14671612&dopt=Abstract
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Effects of age on prognosis with imatinib mesylate therapy for patients with Philadelphia chromosome-positive chronic myelogenous leukemia. Author(s): Cortes J, Talpaz M, O'Brien S, Giles F, Beth Rios M, Shan J, Faderl S, GarciaManero G, Ferrajoli A, Wierda W, Kantarjian H. Source: Cancer. 2003 September 15; 98(6): 1105-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12973833&dopt=Abstract
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Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia. Author(s): O'Brien SG, Meinhardt P, Bond E, Beck J, Peng B, Dutreix C, Mehring G, Milosavljev S, Huber C, Capdeville R, Fischer T. Source: British Journal of Cancer. 2003 November 17; 89(10): 1855-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14612892&dopt=Abstract
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Effects of the tyrosine kinase inhibitor imatinib mesylate on a Bcr-Abl-positive cell line: suppression of autonomous cell growth but no effect on decreased adhesive property and morphological changes. Author(s): Nishihara T, Miura Y, Tohyama Y, Mizutani C, Hishita T, Ichiyama S, Uchiyama T, Tohyama K. Source: International Journal of Hematology. 2003 October; 78(3): 233-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14604282&dopt=Abstract
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Efficacy and safety of imatinib mesylate (Glivec) in combination with interferonalpha (IFN-alpha) in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Author(s): Wassmann B, Scheuring U, Pfeifer H, Binckebanck A, Kabisch A, Lubbert M, Leimer L, Gschaidmeier H, Hoelzer D, Ottmann OG. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 October; 17(10): 1919-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14513038&dopt=Abstract
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Emergence of Ph negative clones in chronic myeloid leukemia (CML) patients in complete cytogenetic remission after therapy with imatinib mesylate (STI). Author(s): Gozzetti A, Tozzuoli D, Crupi R, Gentili S, Bocchia M, Raspadori D, Lauria F. Source: European Journal of Haematology. 2003 October; 71(4): 313-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950245&dopt=Abstract
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Fatal hepatic necrosis following imatinib mesylate therapy. Author(s): Lin NU, Sarantopoulos S, Stone JR, Galinsky I, Stone RM, Deangelo DJ, Soiffer RJ. Source: Blood. 2003 November 1; 102(9): 3455-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14568907&dopt=Abstract
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Finding the next Gleevec: FLT3 targeted kinase inhibitor therapy for acute myeloid leukemia. Author(s): Sawyers CL. Source: Cancer Cell. 2002 June; 1(5): 413-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124170&dopt=Abstract
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First case of immune-mediated haemolytic anaemia associated to imatinib mesylate. Author(s): Novaretti MC, Fonseca GH, Conchon M, Dorlhiac-Llacer PE, Chamone Dde A. Source: European Journal of Haematology. 2003 December; 71(6): 455-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14703696&dopt=Abstract
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Gleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells. Author(s): Boren J, Cascante M, Marin S, Comin-Anduix B, Centelles JJ, Lim S, Bassilian S, Ahmed S, Lee WN, Boros LG. Source: The Journal of Biological Chemistry. 2001 October 12; 276(41): 37747-53. Epub 2001 August 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11489902&dopt=Abstract
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Gleevec does not cross blood-brain barrier. Author(s): Senior K. Source: The Lancet Oncology. 2003 April; 4(4): 198. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681250&dopt=Abstract
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Gleevec for the treatment of chronic myelogenous leukemia: US. Food and Drug Administration regulatory mechanisms, accelerated approval, and orphan drug status. Author(s): Cohen MH, Moses ML, Pazdur R. Source: The Oncologist. 2002; 7(5): 390-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401900&dopt=Abstract
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Gleevec resistance: lessons for target-directed drug development. Author(s): Daley GQ. Source: Cell Cycle (Georgetown, Tex.). 2003 May-June; 2(3): 190-1. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734421&dopt=Abstract
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Gleevec: tailoring to fit. Author(s): May TS. Source: Drug Discovery Today. 2003 March 1; 8(5): 188-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634004&dopt=Abstract
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Gleevec: zeroing in on cancer. Author(s): Capriotti T. Source: Medsurg Nursing : Official Journal of the Academy of Medical-Surgical Nurses. 2002 December; 11(6): 301-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520979&dopt=Abstract
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Gleevec-mediated inhibition of Rad51 expression and enhancement of tumor cell radiosensitivity. Author(s): Russell JS, Brady K, Burgan WE, Cerra MA, Oswald KA, Camphausen K, Tofilon PJ. Source: Cancer Research. 2003 November 1; 63(21): 7377-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14612536&dopt=Abstract
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High-throughput quantification of the anti-leukemia drug STI571 (Gleevec) and its main metabolite (CGP 74588) in human plasma using liquid chromatography-tandem mass spectrometry. Author(s): Bakhtiar R, Lohne J, Ramos L, Khemani L, Hayes M, Tse F. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 March 5; 768(2): 325-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11888061&dopt=Abstract
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Histone deacetylase inhibitor LAQ824 both lowers expression and promotes proteasomal degradation of Bcr-Abl and induces apoptosis of imatinib mesylatesensitive or -refractory chronic myelogenous leukemia-blast crisis cells. Author(s): Nimmanapalli R, Fuino L, Bali P, Gasparetto M, Glozak M, Tao J, Moscinski L, Smith C, Wu J, Jove R, Atadja P, Bhalla K. Source: Cancer Research. 2003 August 15; 63(16): 5126-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941844&dopt=Abstract
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Hypopigmentation in an African patient treated with imatinib mesylate: a case report. Author(s): Hasan S, Dinh K, Lombardo F, Dawkins F, Kark J. Source: Journal of the National Medical Association. 2003 August; 95(8): 722-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934870&dopt=Abstract
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Ida-FLAG plus imatinib mesylate-induced molecular remission in a patient with chemoresistant Ph1+ acute myeloid leukemia. Author(s): Viniou NA, Vassilakopoulos TP, Giakoumi X, Mantzouranis M, Pangalis GA. Source: European Journal of Haematology. 2004 January; 72(1): 58-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14962264&dopt=Abstract
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Images in pathology. Morphologic features of response to Gleevec (Imatinib) treatment of GIST. Author(s): Colecchia M, Diment J. Source: International Journal of Surgical Pathology. 2003 April; 11(2): 119. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754630&dopt=Abstract
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Imatinib mesylate (Gleevec(TM)) reduces phlebotomy requirements in polycythemia vera. Author(s): Silver RT. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 June; 17(6): 1186-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764388&dopt=Abstract
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Imatinib mesylate (Gleevec) in the treatment of 2 patients with Philadelphia-positive ALL relapsing after allogeneic stem cell transplantation. Author(s): Sugimoto K, Mikoshiba M, Ohashi K, Akiyama H, Sakamaki H. Source: International Journal of Hematology. 2002 May; 75(4): 440-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12041679&dopt=Abstract
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Imatinib Mesylate (Gleevec) is a useful agent in the salvage treatment of adults with relapsed/refractory Philadelphia positive acute leukemias. Author(s): Gupta V, Kamel-Reid S, Minden MD, Lipton JH, Brandwein J, Messner HA. Source: Hematology (Amsterdam, Netherlands). 2003 June; 8(3): 139-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745646&dopt=Abstract
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Imatinib mesylate (Gleevec, Glivec): a new therapy for chronic myeloid leukemia and other malignancies. Author(s): Hernandez-Boluda JC, Cervantes F. Source: Drugs Today (Barc). 2002 September; 38(9): 601-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12582448&dopt=Abstract
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Imatinib mesylate (STI 571)--a new oral target therapy for chronic myelogenous leukemia (CML). Author(s): Chrobak L, Voglova J. Source: Acta Medica (Hradec Kralove). 2003; 46(3): 85-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14677715&dopt=Abstract
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Imatinib mesylate (STI-571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumours, but does not yield responses in other soft-tissue sarcomas that are unselected for a molecular target. Results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study. Author(s): Verweij J, van Oosterom A, Blay JY, Judson I, Rodenhuis S, van der Graaf W, Radford J, Le Cesne A, Hogendoorn PC, di Paola ED, Brown M, Nielsen OS. Source: European Journal of Cancer (Oxford, England : 1990). 2003 September; 39(14): 2006-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957454&dopt=Abstract
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Imatinib mesylate (STI571) inhibits multiple myeloma cell proliferation and potentiates the effect of common antimyeloma agents. Author(s): Pandiella A, Carvajal-Vergara X, Tabera S, Mateo G, Gutierrez N, San Miguel JF. Source: British Journal of Haematology. 2003 December; 123(5): 858-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14632777&dopt=Abstract
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Imatinib mesylate affects the development and function of dendritic cells generated from CD34+ peripheral blood progenitor cells. Author(s): Appel S, Boehmler AM, Grunebach F, Muller MR, Rupf A, Weck MM, Hartmann U, Reichardt VL, Kanz L, Brummendorf TH, Brossart P. Source: Blood. 2004 January 15; 103(2): 538-44. Epub 2003 September 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14504105&dopt=Abstract
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Imatinib mesylate as treatment for blastic transformation of Philadelphia chromosome positive chronic myelogenous leukemia. Author(s): Sureda A, Carrasco M, de Miguel M, Martinez JA, Conde E, Sanz MA, DiazMediavilla J, Sierra J. Source: Haematologica. 2003 November; 88(11): 1213-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14607749&dopt=Abstract
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Imatinib mesylate causes hypopigmentation in the skin. Author(s): Tsao AS, Kantarjian H, Cortes J, O'Brien S, Talpaz M. Source: Cancer. 2003 December 1; 98(11): 2483-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14635084&dopt=Abstract
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Imatinib mesylate elicits positive clinical response in atypical chronic myeloid leukemia involving the platelet-derived growth factor receptor beta. Author(s): Garcia JL, Font de Mora J, Hernandez JM, Queizan JA, Gutierrez NC, Hernandez JM, San Miguel JF. Source: Blood. 2003 October 1; 102(7): 2699-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14504072&dopt=Abstract
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Imatinib mesylate in idiopathic and postpolycythemic myelofibrosis. Author(s): Hasselbalch HC, Bjerrum OW, Jensen BA, Clausen NT, Hansen PB, Birgens H, Therkildsen MH, Ralfkiaer E. Source: American Journal of Hematology. 2003 December; 74(4): 238-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14635203&dopt=Abstract
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Imatinib mesylate in Philadelphia chromosome-positive leukemia of childhood. Author(s): Kolb EA, Pan Q, Ladanyi M, Steinherz PG. Source: Cancer. 2003 December 15; 98(12): 2643-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14669284&dopt=Abstract
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Imatinib mesylate therapy improves survival in patients with newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia in the chronic phase: comparison with historic data. Author(s): Kantarjian HM, O'Brien S, Cortes J, Giles FJ, Rios MB, Shan J, Faderl S, Garcia-Manero G, Ferrajoli A, Verstovsek S, Wierda W, Keating M, Talpaz M. Source: Cancer. 2003 December 15; 98(12): 2636-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14669283&dopt=Abstract
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Imatinib mesylate-induced interstitial pneumonitis. Author(s): Ma CX, Hobday TJ, Jett JR. Source: Mayo Clinic Proceedings. 2003 December; 78(12): 1578-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14661689&dopt=Abstract
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Imatinib mesylate-induced maculopapular drug rash. Author(s): Dogra S, Kanwar AJ. Source: Natl Med J India. 2003 September-October; 16(5): 285-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14680290&dopt=Abstract
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In vitro studies of the combination of imatinib mesylate (Gleevec) and arsenic trioxide (Trisenox) in chronic myelogenous leukemia. Author(s): La Rosee P, Johnson K, O'Dwyer ME, Druker BJ. Source: Experimental Hematology. 2002 July; 30(7): 729-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135670&dopt=Abstract
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Insights from pre-clinical studies for new combination treatment regimens with the Bcr-Abl kinase inhibitor imatinib mesylate (Gleevec/Glivec) in chronic myelogenous leukemia: a translational perspective. Author(s): La Rosee P, O'Dwyer ME, Druker BJ. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 July; 16(7): 1213-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094245&dopt=Abstract
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Is there a role for surgery in patients with “unresectable” cKIT+ gastrointestinal stromal tumors treated with imatinib mesylate? Author(s): Scaife CL, Hunt KK, Patel SR, Benjamin RS, Burgess MA, Chen LL, Trent J, Raymond AK, Cormier JN, Pisters PW, Pollock RE, Feig BW. Source: American Journal of Surgery. 2003 December; 186(6): 665-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14672776&dopt=Abstract
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Marked regression of metastatic pilocytic astrocytoma during treatment with imatinib mesylate (STI-571, Gleevec): a case report and laboratory investigation. Author(s): McLaughlin ME, Robson CD, Kieran MW, Jacks T, Pomeroy SL, Cameron S. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2003 August; 25(8): 644-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902920&dopt=Abstract
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Mobilization of Ph chromosome-negative peripheral blood stem cells in chronic myeloid leukaemia patients with imatinib mesylate-induced complete cytogenetic remission. Author(s): Drummond MW, Marin D, Clark RE, Byrne JL, Holyoake TL, Lennard A; United Kingdom Chronic Myeloid Leukaemia (UK CML) Working Party. Source: British Journal of Haematology. 2003 November; 123(3): 479-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14617010&dopt=Abstract
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Molecular characterization and sensitivity of STI-571 (imatinib mesylate, Gleevec)resistant, Bcr-Abl-positive, human acute leukemia cells to SRC kinase inhibitor PD180970 and 17-allylamino-17-demethoxygeldanamycin. Author(s): Nimmanapalli R, O'Bryan E, Huang M, Bali P, Burnette PK, Loughran T, Tepperberg J, Jove R, Bhalla K. Source: Cancer Research. 2002 October 15; 62(20): 5761-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384536&dopt=Abstract
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Molecular remission and reversal of myelofibrosis in response to imatinib mesylate treatment in patients with the myeloproliferative variant of hypereosinophilic syndrome. Author(s): Klion AD, Robyn J, Akin C, Noel P, Brown M, Law M, Metcalfe DD, Dunbar C, Nutman TB. Source: Blood. 2004 January 15; 103(2): 473-8. Epub 2003 September 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14504092&dopt=Abstract
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Molecular response of gastrointestinal stromal tumour after treatment with tyrosine kinase inhibitor imatinib mesylate. Author(s): Reichardt P, Schneider U, Stroszczynski C, Pink D, Hohenberger P. Source: Journal of Clinical Pathology. 2004 February; 57(2): 215-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14747457&dopt=Abstract
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Mycosis fungoides-like reaction in a patient treated with Gleevec. Author(s): Clark SH, Duvic M, Prietol VG. Source: Journal of Cutaneous Pathology. 2003 April; 30(4): 279-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680962&dopt=Abstract
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Myelodysplastic features developing in Philadephia-negative cells during imatinib mesylate therapy for CML: report of a new case. Author(s): Mozziconacci MJ, Cailleres S, Maurice C, Vey N, Sainty D, Blaise D, LafagePochitaloff M. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 September; 17(9): 1901-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970792&dopt=Abstract
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No correlation between the proliferative status of Bcr-Abl positive cell lines and the proapoptotic activity of imatinib mesylate (Gleevec/Glivec). Author(s): La Rosee P, Shen L, Stoffregen EP, Deininger M, Druker BJ. Source: The Hematology Journal : the Official Journal of the European Haematology Association / Eha. 2003; 4(6): 413-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14671613&dopt=Abstract
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Ocular side-effects associated with imatinib mesylate (Gleevec). Author(s): Fraunfelder FW, Solomon J, Druker BJ, Esmaeli B, Kuyl J. Source: Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics. 2003 August; 19(4): 371-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964961&dopt=Abstract
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Oral lichenoid reaction to imatinib (STI 571, Gleevec). Author(s): Lim DS, Muir J. Source: Dermatology (Basel, Switzerland). 2002; 205(2): 169-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218235&dopt=Abstract
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Phase II study of troxacitabine, a novel dioxolane nucleoside analog, in patients with untreated or imatinib mesylate-resistant chronic myelogenous leukemia in blastic phase. Author(s): Giles FJ, Feldman EJ, Roboz GJ, Larson RA, Mamus SW, Cortes JE, Verstovsek S, Faderl S, Talpaz M, Beran M, Albitar M, O'Brien SM, Kantarjian HM. Source: Leukemia Research. 2003 December; 27(12): 1091-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921945&dopt=Abstract
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Philadelphia-negative acute lymphoblastic leukemia developing in a CML patient in imatinib mesylate-induced complete cytogenetic remission. Author(s): Cherrier-De Wilde S, Rack K, Vannuffel P, Delannoy A, Hagemeijer A. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 October; 17(10): 2046-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14513056&dopt=Abstract
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Pityriasis rosea associated with imatinib (STI571, Gleevec). Author(s): Konstantopoulos K, Papadogianni A, Dimopoulou M, Kourelis C, Meletis J. Source: Dermatology (Basel, Switzerland). 2002; 205(2): 172-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218236&dopt=Abstract
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Practical aspects of the treatment of chronic myelogenous leukemia with imatinib mesylate. Author(s): Zonder JA, Schiffer CA. Source: Curr Hematol Rep. 2003 January; 2(1): 57-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901155&dopt=Abstract
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Prediction of initial cytogenetic response for subsequent major and complete cytogenetic response to imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. Author(s): Drummond MW, Holyoake TL. Source: Cancer. 2003 October 15; 98(8): 1776-7; Author Reply 1777-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14534900&dopt=Abstract
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Quantitative polymerase chain reaction monitoring of BCR-ABL during therapy with imatinib mesylate (STI571; gleevec) in chronic-phase chronic myelogenous leukemia. Author(s): Kantarjian HM, Talpaz M, Cortes J, O'Brien S, Faderl S, Thomas D, Giles F, Rios MB, Shan J, Arlinghaus R. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 January; 9(1): 160-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538464&dopt=Abstract
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Relationship between elevated levels of the alpha 1 acid glycoprotein in chronic myelogenous leukemia in blast crisis and pharmacological resistance to imatinib (Gleevec) in vitro and in vivo. Author(s): Larghero J, Leguay T, Mourah S, Madelaine-Chambrin I, Taksin AL, Raffoux E, Bastie JN, Degos L, Berthaud P, Marolleau JP, Calvo F, Chomienne C, Mahon FX, Rousselot P. Source: Biochemical Pharmacology. 2003 November 15; 66(10): 1907-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14599548&dopt=Abstract
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Research on resistance to cancer drug Gleevec. Author(s): Sawyers CL. Source: Science. 2001 November 30; 294(5548): 1834. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11732550&dopt=Abstract
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Results of a prospective phase 2 study combining imatinib mesylate and cytarabine for the treatment of Philadelphia-positive patients with chronic myelogenous leukemia in chronic phase. Author(s): Gardembas M, Rousselot P, Tulliez M, Vigier M, Buzyn A, Rigal-Huguet F, Legros L, Michallet M, Berthou C, Cheron N, Maloisel F, Mahon FX, Facon T, Berthaud P, Guilhot J, Guilhot F; CML French Group. Source: Blood. 2003 December 15; 102(13): 4298-305. Epub 2003 August 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933584&dopt=Abstract
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Role of imatinib mesylate (Gleevec/Glivec) in gastrointestinal stromal tumors. Author(s): de Jong FA, Verweij J. Source: Expert Review of Anticancer Therapy. 2003 December; 3(6): 757-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14686698&dopt=Abstract
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SB-431542 and Gleevec inhibit transforming growth factor-beta-induced proliferation of human osteosarcoma cells. Author(s): Matsuyama S, Iwadate M, Kondo M, Saitoh M, Hanyu A, Shimizu K, Aburatani H, Mishima HK, Imamura T, Miyazono K, Miyazawa K. Source: Cancer Research. 2003 November 15; 63(22): 7791-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14633705&dopt=Abstract
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Severe periorbital edema secondary to STI571 (Gleevec). Author(s): Esmaeli B, Prieto VG, Butler CE, Kim SK, Ahmadi MA, Kantarjian HM, Talpaz M. Source: Cancer. 2002 August 15; 95(4): 881-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209733&dopt=Abstract
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STI571 (Gleevec) as a paradigm for cancer therapy. Author(s): Druker BJ. Source: Trends in Molecular Medicine. 2002; 8(4 Suppl): S14-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927282&dopt=Abstract
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STI-571 (Gleevec) in the treatment of chronic myeloid leukaemia. Author(s): Kumar L, Kumari M, Menon H. Source: Natl Med J India. 2002 September-October; 15(5): 298. No Abstract Available. Erratum In: Natl Med J India. 2002 November-December; 15(6): 350. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12502149&dopt=Abstract
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Successful treatment of extramedullary blast crisis of chronic myelogenous leukemia with imatinib mesylate (STI571). Author(s): Naito K, Mori T, Miyazaki K, Tsukada Y, Ikeda Y, Okamoto S. Source: Intern Med. 2003 August; 42(8): 740-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924504&dopt=Abstract
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The ATP site of protein kinases as target for drug development: from natural compounds to gleevec. Author(s): Granot Y. Source: Isr Med Assoc J. 2002 August; 4(8): 633-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183872&dopt=Abstract
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The emergence of Ph-, trisomy -8+ cells in patients with chronic myeloid leukemia treated with imatinib mesylate. Author(s): Feldman E, Najfeld V, Schuster M, Roboz G, Chadburn A, Silver RT. Source: Experimental Hematology. 2003 August; 31(8): 702-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901975&dopt=Abstract
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The proteasome inhibitor PS-341 inhibits growth and induces apoptosis in Bcr/Ablpositive cell lines sensitive and resistant to imatinib mesylate. Author(s): Gatto S, Scappini B, Pham L, Onida F, Milella M, Ball G, Ricci C, Divoky V, Verstovsek S, Kantarjian HM, Keating MJ, Cortes-Franco JE, Beran M. Source: Haematologica. 2003 August; 88(8): 853-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12935973&dopt=Abstract
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The significance of myelosuppression during therapy with imatinib mesylate in patients with chronic myelogenous leukemia in chronic phase. Author(s): Sneed TB, Kantarjian HM, Talpaz M, O'Brien S, Rios MB, Bekele BN, Zhou X, Resta D, Wierda W, Faderl S, Giles F, Cortes JE. Source: Cancer. 2004 January 1; 100(1): 116-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14692031&dopt=Abstract
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Treatment of inoperable gastrointestinal stromal tumor (GIST) with Imatinib (Glivec, Gleevec). Author(s): Joensuu H. Source: Medizinische Klinik (Munich, Germany : 1983). 2002 January 15; 97 Suppl 1: 2830. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11831069&dopt=Abstract
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Treatment of rheumatoid arthritis with imatinib mesylate: clinical improvement in three refractory cases. Author(s): Eklund KK, Joensuu H. Source: Annals of Medicine. 2003; 35(5): 362-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952023&dopt=Abstract
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Tyrosine kinase inhibitor STI-571/Gleevec down-regulates the beta-catenin signaling activity. Author(s): Zhou L, An N, Haydon RC, Zhou Q, Cheng H, Peng Y, Jiang W, Luu HH, Vanichakarn P, Szatkowski JP, Park JY, Breyer B, He TC. Source: Cancer Letters. 2003 April 25; 193(2): 161-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706873&dopt=Abstract
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CHAPTER 2. NUTRITION AND GLEEVEC Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and Gleevec.
Finding Nutrition Studies on Gleevec 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 “Gleevec” (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 “Gleevec” (or a synonym): •
Activity of the Bcr-Abl kinase inhibitor PD180970 against clinically relevant Bcr-Abl isoforms that cause resistance to imatinib mesylate (Gleevec, STI571). Author(s): Oregon Health and Sciences University Cancer Institute, Division of Hematology and Medical Oncology, Portland, Oregon 97239, USA. Source: La Rosee, P Corbin, A S Stoffregen, E P Deininger, M W Druker, B J Cancer-Res. 2002 December 15; 62(24): 7149-53 0008-5472
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Molecular characterization and sensitivity of STI-571 (imatinib mesylate, Gleevec)resistant, Bcr-Abl-positive, human acute leukemia cells to SRC kinase inhibitor PD180970 and 17-allylamino-17-demethoxygeldanamycin. Author(s): Interdisciplinary Oncology Program, Moffitt Cancer Center, University of South Florida, Tampa 33612, USA. Source: Nimmanapalli, R O'Bryan, E Huang, M Bali, P Burnette, P K Loughran, T Tepperberg, J Jove, R Bhalla, K Cancer-Res. 2002 October 15; 62(20): 5761-9 0008-5472
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Receptor tyrosine kinases as rational targets for prostate cancer treatment: plateletderived growth factor receptor and imatinib mesylate. Author(s): Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
[email protected] Source: George, D J Urology. 2002 September; 60(3 Suppl 1): 115-21; discussion 122 15279995
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/
Nutrition
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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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WebMD®Health: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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CHAPTER 3. ALTERNATIVE MEDICINE AND GLEEVEC Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Gleevec. 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 Gleevec 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 “Gleevec” (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 Gleevec: •
A metabolic hypothesis of cell growth and death in pancreatic cancer. Author(s): Boros LG, Lee WN, Go VL. Source: Pancreas. 2002 January; 24(1): 26-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11741179&dopt=Abstract
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Bcr-Abl-mediated resistance to apoptosis is independent of constant tyrosine-kinase activity. Author(s): Bueno-da-Silva AE, Brumatti G, Russo FO, Green DR, Amarante-Mendes GP. Source: Cell Death and Differentiation. 2003 May; 10(5): 592-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728257&dopt=Abstract
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Beta-hydroxyisovalerylshikonin induces apoptosis in human leukemia cells by inhibiting the activity of a polo-like kinase 1 (PLK1). Author(s): Masuda Y, Nishida A, Hori K, Hirabayashi T, Kajimoto S, Nakajo S, Kondo T, Asaka M, Nakaya K.
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Source: Oncogene. 2003 February 20; 22(7): 1012-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592388&dopt=Abstract •
Comment: Usefulness of herbal and dietary supplement references. Author(s): Burnakis TG. Source: The Annals of Pharmacotherapy. 2003 September; 37(9): 1346. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921528&dopt=Abstract
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Commentary: effect of flavonoids on normal and leukemic cells. Author(s): Faderl S, Estrov Z. Source: Leukemia Research. 2003 June; 27(6): 471-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648504&dopt=Abstract
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Developing therapeutic pharmaceuticals for the treatment of soft-tissue sarcomas. Author(s): Patel SR. Source: Expert Opinion on Investigational Drugs. 2002 December; 11(12): 1789-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457438&dopt=Abstract
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Effects of blocking platelet-derived growth factor-receptor signaling in a mouse model of experimental prostate cancer bone metastases. Author(s): Uehara H, Kim SJ, Karashima T, Shepherd DL, Fan D, Tsan R, Killion JJ, Logothetis C, Mathew P, Fidler IJ. Source: Journal of the National Cancer Institute. 2003 March 19; 95(6): 458-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644539&dopt=Abstract
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Efficacy of SCH66336, a farnesyl transferase inhibitor, in conjunction with imatinib against BCR-ABL-positive cells. Author(s): Nakajima A, Tauchi T, Sumi M, Bishop WR, Ohyashiki K. Source: Molecular Cancer Therapeutics. 2003 March; 2(3): 219-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657715&dopt=Abstract
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Favorable outcome with STI571 (imatinib mesylate) and allogeneic stem cell transplantation in a case of Ph+ chemorefractory acute lymphocytic leukaemia. Author(s): Wernstedt P, Brune M, Andersson PO, Gustavsson B, Stockelberg D, Wadenvik H. Source: Bone Marrow Transplantation. 2002 December; 30(12): 971-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476293&dopt=Abstract
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Flavopiridol potentiates STI571-induced mitochondrial damage and apoptosis in BCR-ABL-positive human leukemia cells. Author(s): Yu C, Krystal G, Dent P, Grant S.
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Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 September; 8(9): 2976-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12231544&dopt=Abstract •
Imatinib in combination with cytarabine for the treatment of Philadelphia-positive chronic myelogenous leukemia chronic-phase patients: rationale and design of phase I/II trials. Author(s): Guilhot F, Gardembas M, Rousselot P, Tulliez M, Vigier M, Buzyn A, RigalHuguet F, Legros L, Michallet M, Berthou C, Najman A, Maloisel F, Mahon FX, Facon T, Berthaud P, Guilhot J; CML French Group. Source: Semin Hematol. 2003 April; 40(2 Suppl 2): 92-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12783382&dopt=Abstract
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Imatinib Mesylate (Gleevec) is a useful agent in the salvage treatment of adults with relapsed/refractory Philadelphia positive acute leukemias. Author(s): Gupta V, Kamel-Reid S, Minden MD, Lipton JH, Brandwein J, Messner HA. Source: Hematology (Amsterdam, Netherlands). 2003 June; 8(3): 139-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745646&dopt=Abstract
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In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents. Author(s): Kano Y, Akutsu M, Tsunoda S, Mano H, Sato Y, Honma Y, Furukawa Y. Source: Blood. 2001 April 1; 97(7): 1999-2007. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11264164&dopt=Abstract
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In vitro effects of STI 571-containing drug combinations on the growth of Philadelphia-positive chronic myelogenous leukemia cells. Author(s): Scappini B, Onida F, Kantarjian HM, Dong L, Verstovsek S, Keating MJ, Beran M. Source: Cancer. 2002 May 15; 94(10): 2653-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173333&dopt=Abstract
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Inhibition of medullary thyroid carcinoma cell proliferation and RET phosphorylation by tyrosine kinase inhibitors. Author(s): Cohen MS, Hussain HB, Moley JF. Source: Surgery. 2002 December; 132(6): 960-6; Discussion 966-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490842&dopt=Abstract
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Inhibition of PDGF receptor signaling in tumor stroma enhances antitumor effect of chemotherapy. Author(s): Pietras K, Rubin K, Sjoblom T, Buchdunger E, Sjoquist M, Heldin CH, Ostman A.
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Source: Cancer Research. 2002 October 1; 62(19): 5476-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359756&dopt=Abstract •
Inhibition of platelet-derived growth factor receptors reduces interstitial hypertension and increases transcapillary transport in tumors. Author(s): Pietras K, Ostman A, Sjoquist M, Buchdunger E, Reed RK, Heldin CH, Rubin K. Source: Cancer Research. 2001 April 1; 61(7): 2929-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11306470&dopt=Abstract
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Inhibition of platelet-derived growth factor-mediated proliferation of osteosarcoma cells by the novel tyrosine kinase inhibitor STI571. Author(s): McGary EC, Weber K, Mills L, Doucet M, Lewis V, Lev DC, Fidler IJ, Bar-Eli M. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 November; 8(11): 3584-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429650&dopt=Abstract
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New agents in cancer clinical trials. Author(s): Adams J, Elliott PJ. Source: Oncogene. 2000 December 27; 19(56): 6687-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11426656&dopt=Abstract
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Phosphatidylinositol-3 kinase inhibitors enhance the anti-leukemia effect of STI571. Author(s): Klejman A, Rushen L, Morrione A, Slupianek A, Skorski T. Source: Oncogene. 2002 August 29; 21(38): 5868-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12185586&dopt=Abstract
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Results of a prospective phase 2 study combining imatinib mesylate and cytarabine for the treatment of Philadelphia-positive patients with chronic myelogenous leukemia in chronic phase. Author(s): Gardembas M, Rousselot P, Tulliez M, Vigier M, Buzyn A, Rigal-Huguet F, Legros L, Michallet M, Berthou C, Cheron N, Maloisel F, Mahon FX, Facon T, Berthaud P, Guilhot J, Guilhot F; CML French Group. Source: Blood. 2003 December 15; 102(13): 4298-305. Epub 2003 August 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933584&dopt=Abstract
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Results of triple therapy with interferon-alpha, cytarabine, and homoharringtonine, and the impact of adding imatinib to the treatment sequence in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in early chronic phase. Author(s): O'Brien S, Giles F, Talpaz M, Cortes J, Rios MB, Shan J, Thomas D, Andreeff M, Kornblau S, Faderl S, Garcia-Manero G, White K, Mallard S, Freireich E, Kantarjian HM.
Alternative Medicine 43
Source: Cancer. 2003 September 1; 98(5): 888-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12942553&dopt=Abstract •
The efficacy of tyrosine kinase inhibitors on human pancreatic cancer cell lines. Author(s): Farivar RS, Gardner-Thorpe J, Ito H, Arshad H, Zinner MJ, Ashley SW, Whang EE. Source: The Journal of Surgical Research. 2003 December; 115(2): 219-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14697287&dopt=Abstract
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The mechanism of Ara-C-induced apoptosis of differentiating cerebellar granule neurons. Author(s): Courtney MJ, Coffey ET. Source: The European Journal of Neuroscience. 1999 March; 11(3): 1073-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10103100&dopt=Abstract
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The third-generation bisphosphonate zoledronate synergistically augments the antiPh+ leukemia activity of imatinib mesylate. Author(s): Kuroda J, Kimura S, Segawa H, Kobayashi Y, Yoshikawa T, Urasaki Y, Ueda T, Enjo F, Tokuda H, Ottmann OG, Maekawa T. Source: Blood. 2003 September 15; 102(6): 2229-35. Epub 2003 May 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763930&dopt=Abstract
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The tyrosine kinase inhibitor CGP 57148 (ST1 571) induces apoptosis in BCR-ABLpositive cells by down-regulating BCL-X. Author(s): Oetzel C, Jonuleit T, Gotz A, van der Kuip H, Michels H, Duyster J, Hallek M, Aulitzky WE. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 May; 6(5): 1958-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10815921&dopt=Abstract
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Unexpected pleural effusions in 3 pediatric patients treated with STI-571. Author(s): Goldsby R, Pulsipher M, Adams R, Coffin C, Albritton K, Wagner L. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2002 November; 24(8): 694-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439048&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.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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WebMD®Health: 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/
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. CLINICAL TRIALS AND GLEEVEC Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning Gleevec.
Recent Trials on Gleevec The following is a list of recent trials dedicated to Gleevec.8 Further information on a trial is available at the Web site indicated. •
A safety and efficacy, open-label study of AG-858 in patients who are cytogenetically positive after treatment with Gleevec(tm). Condition(s): Leukemia, Myeloid, Chronic Study Status: This study is currently recruiting patients. Sponsor(s): Antigenics Purpose - Excerpt: This is a Phase II, open-label study of AG-858 in patients who are cytogenetically positive after treatment with Gleevec. The trial will consist of three independent Phase II evaluations of patient groups according to their cytogenetic status as defined in the eligibility criteria (Eligibility Criteria 4a, 4b, and 4c). Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00058747
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AG-858 and Imatinib Mesylate in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia Who Were Previously Treated With Imatinib Mesylate Condition(s): chronic phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia Study Status: This study is currently recruiting patients.
8
These are listed at www.ClinicalTrials.gov.
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Sponsor(s): Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Vaccines made from a person's white blood cells, such as AG-858, may make the body build an immune response to kill cancer cells. Combining AG-858 with imatinib mesylate may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining AG-858 with imatinib mesylate in treating patients who are currently receiving imatinib mesylate for chronic phase chronic myelogenous leukemia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00070395 •
Arsenic Trioxide and Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia Condition(s): chronic phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Combining chemotherapy with imatinib mesylate may kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of combining arsenic trioxide with imatinib mesylate in treating patients who have chronic phase chronic myelogenous leukemia. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053248
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Chemotherapy, Imatinib Mesylate, and Peripheral Stem Cell Transplantation in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia Condition(s): adult acute lymphoblastic leukemia in remission Study Status: This study is currently recruiting patients. Sponsor(s): Cancer and Leukemia Group B; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Combining imatinib mesylate with chemotherapy and peripheral stem cell transplantation may be an effective treatment for acute lymphoblastic leukemia. PURPOSE: Phase II trial to study the effectiveness of combining imatinib mesylate with chemotherapy and peripheral stem cell transplantation in treating patients who have newly diagnosed acute lymphoblastic leukemia. Phase(s): Phase II
Clinical Trials 47
Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00039377 •
Combination Chemotherapy and Imatinib Mesylate in Treating Children With Relapsed Acute Lymphoblastic Leukemia Condition(s): recurrent childhood acute lymphoblastic leukemia; non-T, non-B childhood acute lymphoblastic leukemia; T-cell childhood acute lymphoblastic leukemia; L2 childhood acute lymphoblastic leukemia; L1 childhood acute lymphoblastic leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Combining more than one chemotherapy drug with imatinib mesylate may kill more cancer cells. PURPOSE: Randomizedphase II trial to study the effectiveness of combination chemotherapy and imatinib mesylate in treating children who have relapsedacute lymphoblastic leukemia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049569
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Combination Chemotherapy and Imatinib Mesylate in Treating Patients With Extensive-Stage Small Cell Lung Cancer Condition(s): extensive stage small cell lung cancer; Recurrent Small Cell Lung Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Princess Margaret Hospital; 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. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining more than one chemotherapy drug with imatinib mesylate may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining cisplatin, irinotecan, and imatinib mesylate in treating patients who have extensive-stage small cell lung cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00052494
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Flavopiridol and Imatinib Mesylate in Treating Patients With Hematologic Cancer Condition(s): accelerated phase chronic myelogenous leukemia; adult acute lymphoblastic leukemia; adult acute myeloid leukemia; blastic phase chronic
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myelogenous leukemia; chronic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Massey Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy such as flavopiridol use different ways to stop cancer cells from dividing so they stop growing or die. Combining imatinib mesylate with flavopiridol may kill more cancer cells. PURPOSE: Phase I trial to study the effectiveness of combining flavopiridol with imatinib mesylate in treating patients who have hematologic cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00064285 •
Fludarabine and Total-Body Irradiation Followed By Donor Peripheral Stem Cell Transplantation in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Has Responded to Treatment With Imatinib Mesylate Condition(s): recurrent childhood acute lymphoblastic leukemia; recurrent adult acute lymphoblastic leukemia; blastic phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; childhood chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Fred Hutchinson Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill cancer cells. Combining imatinib mesylate with fludarabine and total-body irradiation followed by donor peripheral stem cell transplantation may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of fludarabine and total-body irradiation followed by donor peripheral stem cell transplantation in treating patients who have acute lymphoblastic leukemia or chronic myelogenous leukemia that has responded to previous treatment with imatinib mesylate. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00036738
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Imatinib Mesylate (Gleevec; STI571) in Treating Patients With Primary Gastrointestinal Stromal Tumor That Has Been Completely Removed by Surgery Condition(s): gastrointestinal stromal tumor Study Status: This study is currently recruiting patients. Sponsor(s): American College of Surgeons; National Cancer Institute (NCI); National Cancer Institute of Canada; Cancer and Leukemia Group B; Southwest Oncology Group
Clinical Trials 49
Purpose - Excerpt: RATIONALE: Imatinib mesylate (Gleevec; STI571) may interfere with the growth of tumor cells and may be an effective treatment for patients with primarygastrointestinal stromal tumor that has been completely removed by surgery. PURPOSE: Randomizedphase III trial to determine the effectiveness of imatinib mesylate (Gleevec; STI571) in treating patients who have primary gastrointestinal stromal tumor that has been completely removed by surgery. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00041197 •
Imatinib Mesylate and 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Chronic Myelogenous Leukemia Condition(s): blastic phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; accelerated phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Barbara Ann Karmanos Cancer Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy such as 17-N-allylamino-17-demethoxygeldanamycin use different ways to stop cancer cells from dividing so they stop growing or die. Combining imatinib mesylate with chemotherapy may kill more cancer cells. PURPOSE: Phase I trial to study the effectiveness of imatinib mesylate combined with 17-N-allylamino-17demethoxygeldanamycin in treating patients who have chronic myelogenous leukemia. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00066326
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Imatinib Mesylate and Bevacizumab in Treating Patients With Advanced Melanoma or Other Advanced Cancers Condition(s): stage III melanoma; Stage IV Melanoma; Recurrent Melanoma; unspecified adult solid tumor, protocol specific Study Status: This study is currently recruiting patients. Sponsor(s): University of Pennsylvania Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Bevacizumab may stop the growth of tumor cells by stopping blood flow to the tumor. Combining imatinib mesylate with bevacizumab may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combining imatinib mesylate with bevacizumab in treating patients who have advanced melanoma or other metastatic or unresectable cancer. Phase(s): Phase I; Phase II Study Type: Interventional
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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00074308 •
Imatinib Mesylate and Chemotherapy in Treating Patients With Extensive-Stage Small Cell Lung Cancer Condition(s): extensive stage small cell lung cancer Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining imatinib mesylate with chemotherapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining imatinib mesylate with irinotecan and cisplatin in treating patients who have extensive-stage small cell lung cancer Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00045604
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Imatinib Mesylate and Cytarabine in Treating Patients With Newly Diagnosed Chronic Myeloid Leukemia Condition(s): chronic phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Commissie Voor Klinisch Toegepast Onderzoek Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining imatinib mesylate and chemotherapy may kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of imatinib mesylate plus cytarabine in treating patients who have newly diagnosed chronic myeloid leukemia. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00028847
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Imatinib Mesylate and Decitabine in Treating Patients With Chronic Myelogenous Leukemia Condition(s): accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; childhood chronic myelogenous leukemia Study Status: This study is currently recruiting patients.
Clinical Trials 51
Sponsor(s): M.D. Anderson Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining imatinib mesylate with decitabine may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining imatinib mesylate with decitabine in treating patients who have accelerated or blast phasechronic myelogenous leukemia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00054431 •
Imatinib Mesylate and Interferon Alfa in Treating Patients With Chronic Myelogenous Leukemia Condition(s): relapsing chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Oregon Health and Science University; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate and interferon alfa may interfere with the growth of the cancer cells. Combining imatinib mesylate with interferon alfa may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining imatinib mesylate with interferon alfa in treating patients who have chronic myelogenous leukemia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00015847
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Imatinib Mesylate in Treating Patients With Advanced Cancer and Liver Dysfunction Condition(s): adult solid tumor; Gastrointestinal Cancer; hematopoietic and lymphoid cancer Study Status: This study is currently recruiting patients. Sponsor(s): University of Pittsburgh Cancer Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of imatinib mesylate in treating patients who have advanced cancer and liver dysfunction. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025415
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Gleevec
Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia Condition(s): chronic phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; childhood chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have chronic myelogenous leukemia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00030394
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Imatinib Mesylate in Treating Patients With Chronic Myelomonocytic Leukemia or Atypical Chronic Myeloid Leukemia Condition(s): atypical chronic myeloid leukemia; Chronic Myelomonocytic Leukemia Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. PURPOSE: Phase I trial to study the effectiveness of imatinib mesylate in treating patients who have chronic myelomonocytic leukemia or atypical chronic myeloid leukemia. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00079313
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Imatinib Mesylate in Treating Patients With Gliomas Condition(s): adult brain tumor; adult infiltrating astrocytoma; adult noninfiltrating astrocytoma; Adult Oligodendroglioma; Mixed Gliomas Study Status: This study is currently recruiting patients. Sponsor(s): EORTC New Drug Development Group; EORTC Brain Tumor Cooperative Group Purpose - Excerpt: RATIONALE: Imatinib mesylate may interfere with the growth of tumor cells and slow the growth of the tumor. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have gliomas. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00039364
Clinical Trials 53
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Imatinib Mesylate in Treating Patients With Metastatic or Unresectable Merkel Cell Cancer Condition(s): stage III Merkel cell carcinoma; recurrent Merkel cell carcinoma; stage II Merkel cell carcinoma Study Status: This study is currently recruiting patients. Sponsor(s): Southwest Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have metastatic or unresectableMerkel cell cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00068783
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Imatinib Mesylate in Treating Patients With Myelofibrosis Condition(s): Polycythemia Vera; chronic idiopathic Thrombocythemia; Chronic Myelomonocytic Leukemia
myelofibrosis;
Essential
Study Status: This study is currently recruiting patients. Sponsor(s): University of Chicago Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of myelofibrosis by blocking certain enzymes necessary for cell growth. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have myelofibrosis. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00039416 •
Imatinib Mesylate in Treating Patients With Primary or Recurrent Malignant Gastrointestinal Stromal Tumor Condition(s): gastrointestinal stromal tumor Study Status: This study is currently recruiting patients. Sponsor(s): Radiation Therapy Oncology Group; National Cancer Institute (NCI); American College of Radiology Imaging Network; Eastern Cooperative Oncology Group Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Giving imatinib mesylate before and after surgery may be an effective treatment for malignantgastrointestinal stromal tumor. PURPOSE: Phase II trial to study the effectiveness of neoadjuvant and adjuvant imatinib mesylate in treating patients who are undergoing surgery for primary or recurrent malignant gastrointestinal stromal tumor. Phase(s): Phase II
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00028002 •
Imatinib Mesylate in Treating Patients With Recurrent Brain Tumor Condition(s): adult anaplastic oligodendroglioma; adult oligodendroglioma; recurrent adult brain tumor; Mixed Gliomas
well-differentiated
Study Status: This study is currently recruiting patients. Sponsor(s): North Central Cancer Treatment Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have recurrent brain tumor that has not responded to previous surgery and radiation therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049127 •
Imatinib Mesylate in Treating Patients With Recurrent Ewing's Family of Tumors or Desmoplastic Small Round-Cell Tumor Condition(s): recurrent tumors of the Ewing's family Study Status: This study is currently recruiting patients. Sponsor(s): Beckman Research Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have recurrentEwing's family of tumors or desmoplastic small round-cell tumor. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00062205
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Imatinib Mesylate in Treating Patients With Recurrent Malignant Glioma or Meningioma Condition(s): adult brain tumor Study Status: This study is currently recruiting patients. Sponsor(s): North American Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may interfere with the growth of tumor cells and may be an effective treatment for recurrentglioma and meningioma. PURPOSE: Phase I/II trial to study the effectiveness of imatinib mesylate in treating patients who have progressive, recurrent, or unresectablemalignant glioma or meningioma. Phase(s): Phase I; Phase II
Clinical Trials 55
Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00010049 •
Imatinib Mesylate in Treating Patients With Recurrent Meningioma Condition(s): adult anaplastic astrocytoma; adult brain malignant hemangiopericytoma; adult meningioma; adult papillary meningioma; recurrent adult brain tumor Study Status: This study is currently recruiting patients. Sponsor(s): North American Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have recurrentmeningioma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00045734
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Imatinib Mesylate in Treating Patients With Recurrent or Persistent Uterine Carcinosarcoma Condition(s): uterine carcinosarcoma; recurrent uterine sarcoma Study Status: This study is currently recruiting patients. Sponsor(s): Gynecologic Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have recurrent or persistent uterinecarcinosarcoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00075400
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Imatinib Mesylate in Treating Patients With Recurrent Small Cell Lung Cancer Condition(s): Recurrent Small Cell Lung Cancer Study Status: This study is currently recruiting patients. Sponsor(s): North Central Cancer Treatment Group; National Cancer Institute (NCI); Cancer and Leukemia Group B Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have recurrentsmall cell lung cancer. Phase(s): Phase II
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Gleevec
Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00052949 •
Imatinib Mesylate in Treating Patients With Refractory or Relapsed Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer, or Ovarian Low Malignant Potential Tumor Condition(s): recurrent ovarian epithelial cancer; Fallopian Tube Cancer; peritoneal cavity cancer; ovarian low malignant potential tumor Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. PURPOSE: Phase II trial to determine the effectiveness of imatinib mesylate in treating patients who have refractory or relapsedovarian epithelial, fallopian tube, or primaryperitoneal cancer, or ovarian low malignant potential tumor. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00039585
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Imatinib Mesylate in Treating Patients With Relapsed or Refractory Solid Tumors of Childhood Condition(s): Ewing's family of tumors; childhood soft tissue sarcoma; Gastrointestinal Cancer; metastatic cancer; Neuroblastoma; Osteosarcoma Study Status: This study is currently recruiting patients. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have relapsed or refractorysolid tumors of childhood. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00030667
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Imatinib Mesylate in Treating Patients With Stage III or Stage IV Ovarian Epithelial or Primary Peritoneal Cancer Condition(s): stage III ovarian epithelial cancer; stage IV ovarian epithelial cancer; recurrent ovarian epithelial cancer; peritoneal cavity cancer Study Status: This study is currently recruiting patients. Sponsor(s): Southwest Oncology Group; National Cancer Institute (NCI)
Clinical Trials 57
Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have stage III or stage IV ovarian epithelial or primaryperitoneal cancer that has not responded to previous treatment. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00036751 •
Imatinib Mesylate in Treating Patients With Stage IV Colorectal Cancer Condition(s): stage IV colon cancer; Stage IV rectal cancer; recurrent colon cancer; recurrent rectal cancer Study Status: This study is currently recruiting patients. Sponsor(s): M.D. Anderson Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may interfere with the growth of tumor cells by blocking certain enzymes necessary for cancer cell growth. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have stage IV colorectal cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00041340
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Imatinib Mesylate Plus Cytarabine in Treating Patients With Chronic Myelogenous Leukemia Condition(s): chronic phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Oregon Health and Science University; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate plus cytarabine in treating patients who have chronic phase chronic myelogenous leukemia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00022490
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Imatinib Mesylate to Treat Myeloproliferative Hypereosinophilic Syndrome Condition(s): Hypereosinophilic Syndrome Study Status: This study is currently recruiting patients.
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Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will evaluate the safety and effectiveness of imatinib mesylate in reducing the number of eosinophils (a type of white blood cell) in patients with hypereosinophilic syndrome (HES). Patients with HES have elevated counts of eosinophils in the blood and body tissues, which can cause damage to these tissues. Although HES can involve any tissues, the heart, nerves, and skin are most often affected. Several drugs, including steroids, interferon, and hydroxyurea can lower eosinophil counts; however, these drugs have drawbacks in that they do not work in all patients with HES, or they may work only temporarily, or patients may develop side effects that require stopping the drugs. Imatinib mesylate is a new drug approved to treat gastrointestinal tumors and chronic myelogenous leukemia. Some data suggest that imatinib mesylate may be useful in treating a subgroup of patients with HES. Patients with HES who are 18 years of age and older may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood tests, electrocardiogram (EKG), echocardiogram (ultrasound examination of the heart), pulmonary (lung) function tests, and a bone marrow examination to determine if they fall into the subgroup of patients likely to respond to this therapy. For the bone marrow procedure, an area of skin and bone is numbed and a very sharp needle is inserted into the bone to draw out a sample of bone marrow for evaluation under the microscope. Patients enrolled in the study will take imatinib mesylate daily. Any other drugs they may be taking for HES, as well as other drugs they are taking that may interact with imatinib mesylate, will be tapered and stopped. If it is not possible to stop taking certain drugs for other conditions, their dosages may be adjusted. Patients will be monitored weekly with laboratory testing during the first month of treatment and whenever neutrophil counts drop below 1500/mm3 or platelets fall below 100,000/mm3. If blood counts remain high enough, monitoring will be reduced to every 2 weeks for 3 months and once a month after that. Patients will have a clinic visit at NIH 1 month after beginning the drug for a clinical and laboratory evaluation, including a bone marrow examination. Patients whose eosinophil counts are not lowered after 4 weeks of treatment will leave the study. Those who respond to therapy will return to NIH every 3 months for a history and physical examination, laboratory tests, EKG, echocardiogram, and pulmonary function testing to determine how treatment is affecting disease progression. In addition, the following procedures will be done solely for research purposes: - Blood tests to determine the effects of imatinib mesylate on immune cells, including eosinophils. - Leukapheresis to study the effects of imatinib mesylate on eosinophils: For this procedure, whole blood is collected through a needle in an arm vein, similar to donating blood. The blood circulates through a machine that separates it into its components, and the white cells are removed. The rest of the blood is returned to the body, either through the same needle or through another needle in the other arm. - Bone marrow examinations will be done during the screening tests and again 1 month after starting treatment to look at newly developing cells in the bone marrow. - Genetic testing to determine how imatinib mesylate is able to lower eosinophil counts in patients with HES. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044304
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•
Imatinib Mesylate With or Without Interferon Alfa or Cytarabine Compared With Interferon Alfa Followed by Allogeneic Stem Cell Transplantation in Treating Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia Condition(s): chronic phase chronic myelogenous leukemia; childhood chronic myelogenous leukemia Study Status: This study is currently recruiting patients. Sponsor(s): III. Medizinische Klinik Mannheim Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Interferon alfa may interfere with the growth of cancer cells and slow the growth of cancer. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Stem cell transplantation may be able to replace immune cells that were destroyed by cancer therapy. It is not yet known which treatment regimen is most effective in treating chronic myelogenous leukemia. PURPOSE: Randomizedphase III trial to compare the effectiveness of imatinib mesylate with or without interferon alfa or cytarabine compared with interferon alfa followed by allogeneic stem cell transplantation in treating patients who have newly diagnosed chronic phase chronic myelogenous leukemia. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055874
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Imatinib Mesylate With or Without Radiation Therapy in Treating Children With Newly Diagnosed or Recurrent Glioma Condition(s): childhood central nervous system germ cell tumor; high-grade childhood cerebral astrocytoma; untreated childhood brain stem glioma; recurrent childhood brain stem glioma; recurrent childhood cerebral astrocytoma Study Status: This study is currently recruiting patients. Sponsor(s): Pediatric Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may interfere with the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining imatinib mesylate with radiation therapy may kill more tumor cells. PURPOSE: Phase I/II trial to compare the effectiveness of imatinib mesylate with or without radiation therapy in treating children who have newly diagnosed or recurrentglioma. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00021229
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Oblimersen Plus Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia Condition(s): Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia
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Study Status: This study is currently recruiting patients. Sponsor(s): Cancer and Leukemia Group B; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Oblimersen may help imatinib mesylate kill more cancer cells by making cancer cells more sensitive to the drug. PURPOSE: Phase II trial to study the effectiveness of combining oblimersen with imatinib mesylate in treating patients who have chronic myelogenous leukemia that has not responded to previous treatment with imatinib mesylate. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049192 •
Phase I Study of Lonafarnib and Gleevec in Chronic Myelogenous Leukemia Condition(s): Chronic Myelogenous Leukemia Study Status: This study is currently recruiting patients. Sponsor(s): M.D. Anderson Cancer Center Purpose - Excerpt: The purpose of this study if to investigate the effect of lonafarnib (SCH66336) in combination with Gleevec in the treatment of CML. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047502
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Phase I Study of Zarnestra and Gleevec in Chronic Phase Chronic Myelogenous Leukemia Condition(s): Leukemia, Myeloid, Chronic Study Status: This study is currently recruiting patients. Sponsor(s): M.D. Anderson Cancer Center Purpose - Excerpt: The purpose of this study is to investigate the most effective dose of R115777 (Zarnestra) and imatinib mesylate (Gleevec) when used in combination, and the safety of this combination. The possible effect of this combination in Chronic Myelogenous Leukemia (CML) will also be investigated. Patients will also be asked to give a small additional amount of blood and bone marrow whenever one of these procedures is done. The purpose of this is to investigate the effect of this therapy on the leukemia cells and understand better how these drugs work together. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00040105
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Phase II Study of Hyper-CVAD plus Imatinib Mesylate for Philadelphia-Positive Acute Lymphocytic Leukemia Condition(s): Leukemia, Lymphocytic, Acute, L2 Study Status: This study is currently recruiting patients. Sponsor(s): M.D. Anderson Cancer Center Purpose - Excerpt: The goal of this clinical research study if to learn if intensive chemotherapy, combined with imatinib mesylate (Gleevec) given for 8 courses over 6 months, followed by maintenance imatinib mesylate plus chemotherapy for 1 year can improve Philadelphia-positive acute lymphoblastic leukemia. The safety of this treatment will also be studied. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00038610
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Phase II trial of decitabine in patients with chronic myelogenous leukemia accelerated phase who are refractory to imatinib mesylate (Gleevec) Condition(s): Chronic Myelogenous Leukemia Study Status: This study is currently recruiting patients. Sponsor(s): SuperGen Purpose - Excerpt: To determine the safety and efficacy of decitabine in patients with Philadelphia chromosome-positive chronic myelogenous leukemia accelerated phase that were previously treated with imatinib mesylate (STI 571) and became resistant/refractory or were found to be intolerant to the drug. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00041990
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Phase II trial of decitabine in patients with chronic myelogenous leukemia blast phase who are refractory to imatinib mesylate (Gleevec) Condition(s): Chronic Myelogenous Leukemia Study Status: This study is currently recruiting patients. Sponsor(s): SuperGen Purpose - Excerpt: To determine the safety and efficacy of decitabine in patients with Philadelphia chromosome-positive chronic myelogenous leukemia blastic phase that were previously treated with imatinib mesylate (STI 571) and became resistant/refractory or were found to be intolerant to the drug. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042003
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Phase II trial of decitabine in patients with chronic myelogenous leukemia chronic phase who are refractory to imatinib mesylate (Gleevec) Condition(s): Chronic Myelogenous Leukemia Study Status: This study is currently recruiting patients. Sponsor(s): SuperGen Purpose - Excerpt: To determine the safety and efficacy of decitabine in patients with Philadelphia chromosome-positive chronic myelogenous leukemia chronic phase that were previously treated with imatinib mesylate (STI 571) and became resistant/refractory or were found to be intolerant to the drug. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042016
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Phase II Trial of Gleevec in Patients with Advanced Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer Condition(s): Ovarian Neoplasms; Pelvic Neoplasms; Peritoneal Neoplasms Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will evaluate the safety and effectiveness of the experimental drug imatinib (Gleevec, previously known as ST1571) for treating patients with advanced ovarian cancer with or without fallopian tube or primary peritoneal cancer. Gleevec is approved for patients with chronic myeloid leukemia and has shown activity against other leukemias and stomach and intestinal tumors. Its effect on ovarian cancer is not known. Patients with relapsed ovarian cancer or ovarian cancer that does not respond to platinum and taxane-based chemotherapy may be eligible for this study. Patients with fallopian tube or primary peritoneal cancer are also eligible. Candidates will be screened with a medical history, physical examination and computerized tomography (CT) scan or ultrasound to locate the tumor and determine biopsy sites. All participants will undergo tumor biopsies (described below). Participants will take Gleevec capsules twice a day. Patients whose tumors shrink or remain stable without serious side effects may continue to receive treatment. Those whose cancers worsen or who develop severe drug side effects will be taken off the study and counseled about alternative treatments. Patients will have a CT scan or ultrasound study before starting treatment and again every 8 weeks. They will have a needle biopsy or laparoscopy of the tumor before starting treatment and again about 4 weeks into the study to look for characteristics unique to the patient's tumor that might make it more likely to respond to Gleevec. A limited CT of the tumor will be done at the time of the second biopsy. For the biopsy, the area of the procedure is anesthetized and a small needle is inserted through the skin into the tumor. A piece of tissue smaller than the size of a pin is withdrawn through the needle. Laparoscopy is a surgical procedure performed under general anesthesia. It requires making two small holes in the skin through which tubes are inserted to locate the tumor and cut out a small piece of tissue. Patients will have followup visits every 4 weeks, or more often as needed, for a physical examination and blood tests, and review of laboratory studies and drug side effects. Blood tests will be done weekly for the first month of follow-up. Phase(s): Phase II
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035646 •
Randomized Trial of High-Dose Gleevec Alone or in Combination with Peg-Alpha Interferon and GM-CSF in Early Phase CML Condition(s): Leukemia, Myeloid, Chronic Study Status: This study is currently recruiting patients. Sponsor(s): M.D. Anderson Cancer Center Purpose - Excerpt: The goal of this clinical research study is to learn if giving PEG-Alpha Interferon (PEG-Intron) and Sargramostim (GM-CSF) to patients receiving treatment with high dose Gleevec (imatinib mesylate) is more effective in treating CML in chronic phase than therapy with imatinib mesylate alone. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00050531
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Study drug in patients with malignant gist that have progressed during or not tolerated treatment with imatinib mesylate (GLEEVEC(tm)) Condition(s): Gastrointestinal Neoplasms Study Status: This study is currently recruiting patients. Sponsor(s): Pfizer Purpose - Excerpt: The study is for patients with malignant gastrointestinal stromal tumor who have received treatment with imatinib mesylate and either experienced progression of disease or intolerance. Patients will be randomly assigned to receive either study drug or placebo. Patients randomized to receive placebo will be offered crossover to receive study drug at the time their disease progresses on study. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00075218
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Therapy of Hypereosinophilic Syndrome, Polycythemia Vera, Atypical CML or CMML with PDGF-R Fusion Genes, or Mastocytosis with Gleevec Condition(s): Chronic Myelomonocytic Leukemia; Chronic Myeloid Leukemia; Polycythemia Vera; Hypereosinophilic Syndrome; Mastocytosis Study Status: This study is currently recruiting patients. Sponsor(s): M.D. Anderson Cancer Center Purpose - Excerpt: The goal of this clinical research study is to see if Gleevec, known as imatinib mesylate (STI571), can improve the disease condition in patients with hypereosinophilic syndrome, polycythemia vera, atypical CML or CMML with PDGF-R fusion genes, or mastocytosis.
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Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00038675 •
Imatinib Mesylate in Treating Patients With Refractory Metastatic and/or Unresectable Stomach Cancer Condition(s): recurrent gastric cancer; stage IV gastric cancer; adenocarcinoma of the stomach Study Status: This study is not yet open for patient recruitment. Sponsor(s): California Cancer Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have refractorymetastatic and/or unresectable stomach cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00068380
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Imatinib Mesylate With or Without Cytarabine or PEG-Interferon alfa-2a in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia Condition(s): chronic phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia Study Status: This study is not yet open for patient recruitment. Sponsor(s): Southwest Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy, such as cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Biological therapies, such as PEG-interferon alfa-2a, may interfere with the growth of cancer cells and slow the growth of cancer. It is not yet known whether imatinib mesylate is more effective given in higher doses or combined with either cytarabine or PEG-interferon alfa-2a in treating chronic phase chronic myelogenous leukemia. PURPOSE: Randomizedphase II trial to compare the effectiveness of imatinib mesylate with or without cytarabine or PEG-interferon alfa-2a in treating patients who have previously untreated chronic phase chronic myelogenous leukemia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00070499
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Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “Gleevec” (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 5. PERIODICALS AND NEWS ON GLEEVEC Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Gleevec.
News Services and Press Releases One of the simplest ways of tracking press releases on Gleevec 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 “Gleevec” (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 Gleevec. 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 “Gleevec” (or synonyms). The following was recently listed in this archive for Gleevec: •
Novartis says response better on high Gleevec dose Source: Reuters Industry Breifing Date: December 09, 2003
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Gleevec may treat other leukemias, US study shows Source: Reuters Health eLine Date: December 09, 2003
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Gleevec may treat leukemias other than CML Source: Reuters Medical News Date: December 09, 2003
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Gleevec inhibits proliferation of aggressive neuroblastomas Source: Reuters Industry Breifing Date: August 13, 2003
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SuperGen to combine cancer drug with Gleevec in CML trial Source: Reuters Industry Breifing Date: June 13, 2003
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Gleevec wins pediatric leukemia indication Source: Reuters Medical News Date: May 21, 2003
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Gleevec wins pediatric leukemia approval Source: Reuters Health eLine Date: May 21, 2003
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Novartis' Gleevec wins pediatric leukemia indication Source: Reuters Industry Breifing Date: May 20, 2003
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FDA clears Novartis to market Gleevec tablets Source: Reuters Industry Breifing Date: April 21, 2003
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Phase II trial of personalized CML vaccine plus Gleevec under way Source: Reuters Medical News Date: April 09, 2003
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Gleevec yields 80% response rate in gastrointestinal stromal tumours Source: Reuters Industry Breifing Date: March 14, 2003
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Gleevec cannot control CNS leukemia in mouse model Source: Reuters Medical News Date: March 10, 2003
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Gleevec thwarts bone tumor in mice: study Source: Reuters Health eLine Date: December 25, 2002
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Gleevec thwarts bone tumor in mice -- study Source: Reuters Industry Breifing Date: December 25, 2002
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FDA clears Novartis' Gleevec as first-line CML treatment Source: Reuters Medical News Date: December 23, 2002
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Imatinib mesylate shows promise as treatment for some forms of AML Source: Reuters Industry Breifing Date: December 09, 2002
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Imatinib mesylate effective in a case of inoperable dermatofibrosarcoma Source: Reuters Industry Breifing Date: September 24, 2002
Periodicals and News
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Case of severe periorbital edema linked to treatment with Gleevec Source: Reuters Industry Breifing Date: August 23, 2002
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Gleevec and other c-Kit inhibitors might treat Kaposi's sarcoma Source: Reuters Industry Breifing Date: August 22, 2002
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FDA gives Gleevec priority review as first-line CML treatment Source: Reuters Industry Breifing Date: August 22, 2002
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Imatinib mesylate shows promise as treatment for myeloproliferative diseases Source: Reuters Industry Breifing Date: August 14, 2002
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Gleevec may fight broader range of cancers Source: Reuters Health eLine Date: August 14, 2002
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Novartis' Gleevec may restore color to gray hair, French doctors say Source: Reuters Industry Breifing Date: August 08, 2002
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Imatinib mesylate may alter natural history of chronic-phase CML Source: Reuters Industry Breifing Date: July 26, 2002
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Gleevec blocks progression of early-stage CML Source: Reuters Medical News Date: May 21, 2002
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Novartis' Gleevec beats interferon at treating early-stage CML in study Source: Reuters Industry Breifing Date: May 20, 2002
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Gleevec helps fight leukemia early on: report Source: Reuters Health eLine Date: May 20, 2002
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UK says evidence lacking for widespread use of imatinib mesylate Source: Reuters Medical News Date: May 14, 2002
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Gleevec gets FDA okay for new cancer indication Source: Reuters Health eLine Date: February 04, 2002
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Novartis' Gleevec wins GIST indication from FDA Source: Reuters Industry Breifing Date: February 01, 2002
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FDA approves Gleevec for gastrointestinal stromal cancer Source: Reuters Medical News Date: February 01, 2002
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Novartis seeks FDA approval of Gleevec for gastrointestinal tumors Source: Reuters Industry Breifing Date: October 19, 2001
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Novartis shares fall after new Gleevec study Source: Reuters Industry Breifing Date: June 22, 2001
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Cancer resistance to Gleevec caused by reactivation of BCR-ABL gene Source: Reuters Medical News Date: June 21, 2001
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Express Scripts to provide patient assistance services for Novartis' Gleevec Source: Reuters Industry Breifing Date: May 31, 2001
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Novartis' Gleevec shows powerful response against solid tumors Source: Reuters Industry Breifing Date: May 14, 2001
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Novartis' Gleevec wins US approval after less than 3-month review Source: Reuters Industry Breifing Date: May 10, 2001 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 “Gleevec” (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. 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
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you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “Gleevec” (or synonyms). If you know the name of a company that is relevant to Gleevec, 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 “Gleevec” (or synonyms).
Academic Periodicals covering Gleevec Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to Gleevec. In addition to these sources, you can search for articles covering Gleevec 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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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 Institute9: •
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/
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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.10 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:11 •
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
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
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
•
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/
•
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
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
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
10
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). 11 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
•
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 NLM Gateway12 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.13 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Gleevec” (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 1015 4 295 0 6 1320
HSTAT14 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.15 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.16 Simply search by “Gleevec” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
12
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
13
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). 14 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 15 16
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.
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Coffee Break: Tutorials for Biologists17 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.18 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.19 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/.
17 Adapted 18
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
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. 19 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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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 Gleevec 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 Gleevec. 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 Gleevec. 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 “Gleevec”:
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Other guides Bone Cancer http://www.nlm.nih.gov/medlineplus/bonecancer.html Cancer http://www.nlm.nih.gov/medlineplus/cancer.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 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 “Gleevec” (or synonyms). The following was recently posted: •
Adjuvant chemotherapy following complete resection of soft tissue sarcoma in adults Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 2000 (revised online 2002 Oct); 27 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3488&nbr=2714&a mp;string=imatinib+AND+mesylate
•
Chemotherapy and biotherapy: guidelines and recommendations for practice Source: Oncology Nursing Society - Professional Association; 2001; 226 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3209&nbr=2435&a mp;string=Gleevec 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 Gleevec. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.
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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
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
•
Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
•
Med Help International: http://www.medhelp.org/HealthTopics/A.html
•
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
•
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMD®Health: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Gleevec. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Gleevec. 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 Gleevec. 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 “Gleevec” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received
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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 “Gleevec”. 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 “Gleevec” (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 “Gleevec” (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.20
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
20
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)21: •
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
•
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
•
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
•
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/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
•
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/
•
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/
21
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries 87 •
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
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
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
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
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
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
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/
•
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
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
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/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries 89 •
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
•
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
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
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
•
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/
•
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/
•
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
•
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).
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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GLEEVEC DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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] Accelerated phase: Refers to chronic myelogenous leukemia that is progressing. The number of immature, abnormal white blood cells in the bone marrow and blood is higher than in the chronic phase, but not as high as in the blast phase. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]
Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [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] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of
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antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] 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] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] 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] 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] 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] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] 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]
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Anaplastic: A term used to describe cancer cells that divide rapidly and bear little or no resemblance to normal cells. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] 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]
Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores may become infected from ingestion of infected carcasses. It is transmitted to humans by contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] 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] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Apoptosis: One of the two mechanisms by which cell pathological process of necrosis). Apoptosis is the physiological deletion of cells and appears to be characterized by distinctive morphologic changes in the
death occurs (the other being the mechanism responsible for the intrinsically programmed. It is nucleus and cytoplasm, chromatin
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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] Arsenic trioxide: An anticancer drug that induces programmed cell death (apoptosis) in certain cancer cells. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [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] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [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] 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] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [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] Bevacizumab: A monoclonal antibody that may prevent the growth of blood vessels from surrounding tissue to a solid tumor. [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
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fats in the duodenum. [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 Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blast Crisis: Rapid increase in the proportion of blast cells in the blood and bone marrow. [NIH]
Blast phase: The phase of chronic myelogenous leukemia in which the number of immature, abnormal white blood cells in the bone marrow and blood is extremely high. Also called blast crisis. [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] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells,
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megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone Marrow Examination: Removal of bone marrow and evaluation of its histologic picture. [NIH] Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [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 Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Brain stem glioma: A tumor located in the part of the brain that connects to the spinal cord (the brain stem). It may grow rapidly or slowly, depending on the grade of the tumor. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [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] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] 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] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [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]
Carcinosarcoma: A malignant tumor that is a mixture of carcinoma (cancer of epithelial tissue, which is skin and tissue that lines or covers the internal organs) and sarcoma (cancer of connective tissue, such as bone, cartilage, and fat). [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH]
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Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter 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 proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [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] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [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] 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] Chemotherapy: Treatment with anticancer drugs. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] 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] Chromosome Aberrations: Deviations from the normal number or structure of chromosomes, not necessarily associated with disease. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH]
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Chronic Disease: Disease or ailment of long duration. [NIH] Chronic granulocytic leukemia: A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myelogenous leukemia or chronic myeloid leukemia. [NIH] Chronic lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [NIH] Chronic myelogenous leukemia: CML. A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myeloid leukemia or chronic granulocytic leukemia. [NIH] Chronic phase: Refers to the early stages of chronic myelogenous leukemia or chronic lymphocytic leukemia. The number of mature and immature abnormal white blood cells in the bone marrow and blood is higher than normal, but lower than in the accelerated or blast phase. [NIH] Chronic phase chronic myelogenous leukemia: A phase of chronic myelogenous leukemia that may last from several months to several years. Although there may be no symptoms of leukemia, there are too many white blood cells. [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] 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]
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] 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] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [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
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C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH] 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 axial 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 CAT scan, computed tomography (CT scan), or computerized tomography. [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] Conjugated: Acting or operating as if joined; simultaneous. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective
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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] 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] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [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] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclin: Molecule that regulates the cell cycle. [NIH] Cytarabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]
Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Daunorubicin:
Very
toxic
anthracycline
aminoglycoside
antibiotic
isolated
from
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Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
Decision Trees: A graphic device used in decision analysis, series of decision options are represented as branches (hierarchical). [NIH] Decitabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]
Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] 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]
Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [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] 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] 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] Dose-limiting: Describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. [NIH] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular
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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] Duodenum: The first part of the small intestine. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [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] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [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] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most
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species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythroid Progenitor Cells: Committed, erythroid stem cells derived from myeloid stem cells. The progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E). BFU-E differentiate into CFU-E on stimulation by erythropoietin, and then further differentiate into erythroblasts when stimulated by other factors. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extensive-stage small cell lung cancer: Cancer that has spread outside the lung to other tissues in the chest or to other parts of the body. [NIH] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] 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] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Farnesyl: Enzyme which adds 15 carbon atoms to the Ras precursor protein. [NIH] Fat: Total lipids including phospholipids. [NIH] 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] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fludarabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [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
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diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] 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] 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] Gastrointestinal: Refers to 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 Amplification: A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development. [NIH] 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 testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [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]
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Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
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] Glycoprotein: A protein that has sugar molecules attached to it. [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] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [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] 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] Hemangiopericytoma: A type of cancer involving blood vessels and soft tissue. [NIH] Hematopoietic Stem Cell Transplantation: The transference of stem cells from one animal or human to another (allogeneic), or within the same individual (autologous). The source for the stem cells may be the bone marrow or peripheral blood. Stem cell transplantation has been used as an alternative to autologous bone marrow transplantation in the treatment of a variety of neoplasms. [NIH] Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatic: Refers to the liver. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] 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]
Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform
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quality throughout. [EU] Homoharringtonine: An anticancer drug that belongs to the plant alkaloid family of drugs. [NIH]
Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] 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] Host: Any animal that receives a transplanted graft. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [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] Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypopigmentation: A condition caused by a deficiency in melanin formation or a loss of pre-existing melanin or melanocytes. It can be complete or partial and may result from trauma, inflammation, and certain infections. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Idiopathic myelofibrosis: A progressive disease in which the bone marrow is replaced by fibrous tissue and is unable to produce red blood cells; the cause is unknown. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
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]
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Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophenotyping: Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort Tlymphocytes into subsets based on CD antigens by the technique of flow cytometry. [NIH] 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] 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] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] 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] 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]
Inflammation: A pathological process characterized by injury or destruction of tissues
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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] Inoperable: Not suitable to be operated upon. [EU] 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] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon Alfa-2a: A recombinant alfa interferon consisting of 165 amino acids with lysine at position 23 and histidine at position 34. It is used extensively as an antiviral and antineoplastic agent. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] 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] 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]
Irinotecan: An anticancer drug that belongs to a family of anticancer drugs called topoisomerase inhibitors. It is a camptothecin analogue. Also called CPT 11. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] 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]
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Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laparoscopy: Examination, therapy or surgery of the abdomen's interior by means of a laparoscope. [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] Leiomyosarcoma: A tumor of the muscles in the uterus, abdomen, or pelvis. [NIH] Lentivirus: A genus of the family Retroviridae consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] 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] Leukocytosis: A transient increase in the number of leukocytes in a body fluid. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Lipid: Fat. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver metastases: Cancer that has spread from the original (primary) tumor to the liver. [NIH]
Localized: Cancer which has not metastasized yet. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph
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nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Maculopapular: Both macular and papular, as an eruption consisting of both macules and papules; sometimes erroneously used to designate a papule that is only slightly elevated. [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] Mastocytosis: A group of diseases resulting from proliferation of mast cells. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [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] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] 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
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protect the brain and spinal cord. Meningiomas usually grow slowly. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] 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] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] 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] 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] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] 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]
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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] 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] Morphological: Relating to the configuration or the structure of live organs. [NIH] Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Myelodysplastic syndrome: Disease in which the bone marrow does not function normally. Also called preleukemia or smoldering leukemia. [NIH] Myelofibrosis: A disorder in which the bone marrow is replaced by fibrous tissue. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myeloid Progenitor Cells: One of the two stem cells derived from hematopoietic stem cells the other being the lymphoid progenitor cell. Derived from these myeloid progenitor cells are the erythroid progenitor cells and the myeloid cells (monocytes and granulocytes). [NIH] Myelosuppression: A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of some cancer treatments. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [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] 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] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [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] 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] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with
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other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] 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] 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] Neutrophil: A type of white blood cell. [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] 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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Oligodendroglial: A cell that lays down myelin. [NIH] Oligodendroglioma: A rare, slow-growing tumor that begins in brain cells called oligodendrocytes, which provide support and nourishment for cells that transmit nerve impulses. Also called oligodendroglial tumor. [NIH] Oncogenes: Genes which can potentially induce neoplastic transformation. They include genes for growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. When these genes are constitutively expressed after structural and/or regulatory changes, uncontrolled cell proliferation may result. Viral oncogenes have prefix "v-" before the gene symbol; cellular oncogenes (protooncogenes) have the prefix "c-" before the gene symbol. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [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] Osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma. [NIH] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH]
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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] Ovum: A female germ cell extruded from the ovary at ovulation. [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]
Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] 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] Papilla: A small nipple-shaped elevation. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Papule: A small circumscribed, superficial, solid elevation of the skin. [EU] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] 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] Pelvic: Pertaining to the pelvis. [EU] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] 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] 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),
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or syngeneic (blood cells donated by an identical twin). Also called peripheral stem cell support. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] 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] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phlebotomy: The letting of blood from a vein. Although it is one of the techniques used in drawing blood to be used in diagnostic procedures, in modern medicine, it is used commonly in the treatment of erythrocytosis, hemochromocytosis, polycythemia vera, and porphyria cutanea tarda. Its historical counterpart is bloodletting. (From Cecil Textbook of Medicine, 19th ed & Wintrobe's Clinical Hematology, 9th ed) Venipuncture is not only for the letting of blood from a vein but also for the injecting of a drug into the vein for diagnostic analysis. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [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] Phosphorylate: 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] Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [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
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cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilocytic: Made up of cells that look like fibers when viewed under a microscope. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alphagranules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. [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]
Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pleural Effusion: Presence of fluid in the pleural cavity resulting from excessive transudation or exudation from the pleural surfaces. It is a sign of disease and not a diagnosis in itself. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Polycythemia Vera: A myeloproliferative disorder of unknown etiology, characterized by abnormal proliferation of all hematopoietic bone marrow elements and an absolute increase in red cell mass and total blood volume, associated frequently with splenomegaly, leukocytosis, and thrombocythemia. Hematopoiesis is also reactive in extramedullary sites
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(liver and spleen). In time myelofibrosis occurs. [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] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]
Porphyria Cutanea Tarda: A form of hepatic porphyria (porphyria, hepatic) characterized by photosensitivity resulting in bullae that rupture easily to form shallow ulcers. This condition occurs in two forms: a sporadic, nonfamilial form that begins in middle age and has normal amounts of uroporphyrinogen decarboxylase with diminished activity in the liver; and a familial form in which there is an autosomal dominant inherited deficiency of uroporphyrinogen decarboxylase in the liver and red blood cells. [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] 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] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH]
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Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] 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] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [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] 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] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] 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] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [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] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH]
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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] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [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] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating 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]
Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] 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] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] 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] 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] Reactivation: The restoration of activity to something that has been inactivated. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and
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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] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Residual disease: Cancer cells that remain after attempts have been made to remove the cancer. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Ribonucleoside Diphosphate Reductase: An enzyme of the oxidoreductase class that catalyzes the formation of 2'-deoxyribonucleotides from the corresponding ribonucleotides
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using NADPH as the ultimate electron donor. The deoxyribonucleoside diphosphates are used in DNA synthesis. (From Dorland, 27th ed) EC 1.17.4.1. [NIH] Rod: A reception for vision, located in the retina. [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] Screening: Checking for disease when there are no symptoms. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] 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] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [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 receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH]
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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] Smoldering leukemia: Disease in which the bone marrow does not function normally. Also called preleukemia or myelodysplastic syndrome. [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] 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 cells: All the body cells except the reproductive (germ) cells. [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] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [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] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [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]
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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] 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] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Stromal tumors: Tumors that arise in the supporting connective tissue of an organ. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [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] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Symphysis: A secondary cartilaginous joint. [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] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] 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] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH]
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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] 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] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [NIH] Total-body irradiation: Radiation therapy to the entire body. Usually followed by bone marrow or peripheral stem cell transplantation. [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] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] 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] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [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] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]
Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]
Troxacitabine: A drug being studied for use as an anticancer agent. [NIH]
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Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Unresectable: Unable to be surgically removed. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [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] 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] 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] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] 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] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] 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]
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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] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zoledronate: A drug that belongs to the family of drugs called bisphosphonates. It is used to prevent bone fractures and reduce bone pain in people who have cancer that has spread to the bone. [NIH] Zygote: The fertilized ovum. [NIH]
129
INDEX A Abdominal, 20, 93, 103, 116, 117, 122 Accelerated phase, 5, 9, 47, 49, 50, 61, 93 Acute leukemia, 10, 25, 28, 36, 41, 93, 120 Acute lymphoblastic leukemia, 22, 30, 46, 47, 48, 61, 93 Acute lymphocytic leukemia, 93 Acute myelogenous leukemia, 93 Acute myeloid leukemia, 23, 25, 47, 93 Acute nonlymphocytic leukemia, 93 Adaptability, 93, 99 Adenocarcinoma, 16, 64, 93 Adjuvant, 53, 82, 93 Adrenal Cortex, 93, 120 Adverse Effect, 93, 123 Affinity, 93, 94, 96 Agonist, 16, 94 Algorithms, 8, 94, 97 Alkaloid, 94, 98, 108 Alleles, 9, 94 Allogeneic, 8, 20, 21, 25, 40, 59, 94, 107, 116 Alpha Particles, 94, 121 Alternative medicine, 70, 94 Amino Acid Sequence, 94, 95, 106 Amino Acids, 94, 106, 110, 115, 116, 120 Anaemia, 23, 94 Anaesthesia, 94, 109 Analog, 29, 94 Analogous, 94, 104, 126 Anaphylatoxins, 94, 101 Anaplastic, 21, 54, 55, 95 Anemia, 95, 114 Anesthesia, 62, 95 Animal model, 4, 95 Annealing, 95, 119 Anthrax, 4, 95 Antibiotic, 95, 102, 103 Antibodies, 5, 16, 95, 109, 112, 118, 121 Antibody, 5, 94, 95, 96, 100, 108, 109, 110, 114, 121, 124, 128 Antigen, 4, 8, 16, 93, 95, 101, 103, 108, 109 Antigen-Antibody Complex, 95, 101 Antigen-presenting cell, 95, 103 Antineoplastic, 95, 103, 108, 110 Antiviral, 95, 109, 110 Anus, 95, 98, 122
Apoptosis, 9, 10, 11, 12, 24, 32, 39, 40, 43, 95, 96, 98 Arsenic trioxide, 27, 46, 96 Arterial, 96, 108, 120, 125 Arteries, 96, 97, 102, 113 Arterioles, 96, 97, 98 Assay, 4, 5, 7, 8, 96 Astrocytes, 96 Astrocytoma, 28, 52, 55, 59, 96 Atypical, 26, 52, 63, 96 Autologous, 8, 96, 107, 116 Autologous bone marrow transplantation, 96, 107 B Bacillus, 4, 95, 96 Bacteria, 95, 96, 113, 118, 126, 127 Bacteriophage, 96, 126 Bacterium, 4, 96 Base, 96, 102, 103, 106, 110 Bevacizumab, 49, 96 Bile, 96, 106, 111, 124 Biochemical, 4, 30, 94, 97, 105, 117 Biological response modifier, 97, 110 Biological Transport, 97, 103 Biopsy, 62, 97 Biosynthesis, 97, 111, 123 Biotechnology, 16, 17, 70, 77, 97 Biotransformation, 97 Bladder, 97, 120, 127 Blast Crisis, 5, 9, 10, 12, 21, 24, 30, 32, 97 Blast phase, 12, 51, 61, 93, 97, 100 Blood pressure, 97, 108, 114 Blood vessel, 16, 96, 97, 104, 107, 112, 116, 124, 125, 127 Blood Volume, 97, 118 Blood-Brain Barrier, 23, 97 Bone Marrow Cells, 15, 97, 112 Bone Marrow Examination, 58, 98 Bone metastases, 40, 98 Bowel, 98, 103, 110, 117 Bowel Movement, 98, 103 Brachytherapy, 98, 110, 121, 128 Brain Stem, 59, 98, 99 Brain stem glioma, 59, 98 Branch, 89, 98, 112, 116, 124, 125 Breakdown, 98, 103, 106, 123 C Calcium, 98, 100, 123
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Camptothecin, 98, 110 Capillary, 21, 98, 127 Capsules, 62, 98 Carcinogenesis, 6, 98, 117 Carcinogenic, 98, 115, 124 Carcinoma, 21, 41, 53, 98 Carcinosarcoma, 55, 98 Case report, 24, 28, 98 Caspase, 9, 98 Cell Cycle, 9, 24, 99, 100, 102, 121 Cell Death, 12, 39, 95, 96, 99, 114 Cell Differentiation, 99, 123 Cell Division, 96, 99, 107, 113, 118 Cell Extracts, 5, 99 Cell proliferation, 26, 41, 99, 115, 123 Cell Size, 99, 105 Cell Transplantation, 21, 46, 48, 59, 99 Central Nervous System, 59, 99, 119 Cerebellar, 43, 99 Cerebellum, 99, 119 Cerebral, 59, 97, 98, 99, 105 Cerebral hemispheres, 98, 99 Cerebrum, 99 Chemotactic Factors, 99, 101 Chemotherapy, 6, 20, 22, 41, 46, 47, 48, 49, 50, 51, 57, 59, 61, 62, 64, 82, 99 Cholesterol, 96, 99, 111, 123, 124 Chromatin, 9, 95, 99 Chromosomal, 5, 9, 19, 99, 118 Chromosome, 4, 9, 11, 18, 19, 20, 22, 26, 27, 28, 30, 42, 45, 46, 48, 49, 50, 51, 52, 57, 59, 61, 62, 64, 99, 106, 126 Chromosome Aberrations, 19, 99 Chronic Disease, 100, 111 Chronic granulocytic leukemia, 100 Chronic lymphocytic leukemia, 100 Chronic phase, 5, 18, 19, 27, 31, 32, 42, 45, 46, 48, 49, 50, 51, 52, 57, 59, 62, 63, 64, 93, 100 Chronic phase chronic myelogenous leukemia, 45, 46, 48, 49, 50, 51, 52, 57, 59, 64, 100 Cisplatin, 16, 47, 50, 100 Clinical trial, 3, 12, 14, 42, 45, 65, 77, 100, 120, 121 Clone, 5, 100 Cloning, 97, 100 Coenzyme, 100, 111, 123 Cofactor, 100, 120 Colorectal, 57, 100 Colorectal Cancer, 57, 100 Combination chemotherapy, 47, 100
Complement, 16, 94, 100, 101 Complementary and alternative medicine, 39, 44, 101 Complementary medicine, 39, 101 Complete remission, 101, 122 Complete response, 10, 101 Computational Biology, 77, 101 Computed tomography, 101 Computerized axial tomography, 101 Computerized tomography, 62, 101 Conjugated, 101, 102 Connective Tissue, 97, 98, 101, 102, 122, 123, 125 Contraindications, ii, 102 Cornea, 102, 125 Coronary, 102, 113 Coronary Thrombosis, 102, 113 Corpus, 102, 120 Corpus Luteum, 102, 120 Curative, 102, 125 Cutaneous, 21, 29, 95, 102 Cyclin, 9, 102 Cytarabine, 31, 41, 42, 50, 57, 59, 64, 102 Cytochrome, 22, 102 Cytokine, 12, 102 Cytoplasm, 95, 102, 104, 107, 114 Cytosine, 9, 102 Cytotoxic, 8, 10, 20, 41, 102, 121, 123 Cytotoxicity, 100, 102 D Databases, Bibliographic, 77, 102 Daunorubicin, 102, 103 Decision Trees, 8, 103 Decitabine, 50, 51, 61, 62, 103 Deletion, 14, 95, 103 Denaturation, 103, 119 Dendrites, 103, 115 Dendritic, 26, 103, 112 Dendritic cell, 26, 103 Density, 103, 105, 111 Depolarization, 103, 123 Diagnostic procedure, 70, 103, 117 Diaphragm, 103, 118 Diastolic, 103, 108 Diffusion, 15, 97, 103 Digestion, 96, 98, 103, 110, 111, 125 Digestive system, 65, 103 Diploid, 103, 118, 126 Direct, iii, 9, 21, 103, 122 Disease Progression, 5, 9, 58, 103 Dose-limiting, 9, 103 Doxorubicin, 6, 103
Index 131
Drug Design, 15, 103 Drug Interactions, 104 Drug Resistance, 4, 5, 104 Drug Tolerance, 104 Duodenum, 96, 104, 125 E Edema, 4, 31, 69, 104 Effector, 4, 100, 104 Efficacy, 4, 5, 11, 14, 22, 40, 43, 45, 61, 62, 103, 104, 126 Electrocardiogram, 58, 104 Electrons, 96, 104, 116, 121 Embryo, 99, 104, 109 Endothelial cell, 97, 104 Endotoxins, 101, 104 Environmental Health, 76, 78, 104 Enzymatic, 4, 98, 101, 104, 119 Enzyme, 23, 98, 100, 103, 104, 105, 111, 119, 120, 122, 123, 125, 127 Eosinophil, 58, 104 Eosinophilic, 104 Epinephrine, 104, 127 Epithelial, 15, 56, 57, 93, 97, 98, 105 Erythrocytes, 94, 95, 97, 105, 122 Erythroid Progenitor Cells, 105, 114 Esophagus, 103, 105, 125 Excitation, 105 Exogenous, 97, 105 Extensive-stage small cell lung cancer, 47, 50, 105 External-beam radiation, 105, 110, 121, 128 Extremity, 7, 105 Eye socket, 105, 116 F Family Planning, 77, 105 Farnesyl, 40, 105 Fat, 97, 98, 105, 111, 122, 124 Fine-needle aspiration, 105, 114 Flavopiridol, 9, 40, 47, 48, 105 Flow Cytometry, 6, 10, 105, 109 Fludarabine, 48, 105 Fluorescence, 105, 106 Fluorescent Dyes, 105, 106 Foramen, 106, 117 Fungi, 106, 113, 124, 128 G Gallbladder, 93, 103, 106 Gamma Rays, 106, 121 Gas, 103, 106, 108 Gastric, 64, 106
Gastrointestinal, 6, 18, 20, 26, 28, 31, 32, 48, 49, 51, 53, 56, 58, 63, 68, 69, 105, 106, 125 Gene, 4, 6, 7, 9, 11, 13, 14, 20, 70, 94, 97, 106, 115 Gene Amplification, 14, 106 Gene Expression, 6, 7, 20, 106 Gene Rearrangement, 13, 106 Genetic Code, 106, 115 Genetic testing, 58, 106, 119 Genotype, 106, 117 Gland, 93, 106, 116, 120, 123, 124, 126 Glioma, 14, 54, 59, 106 Glomerular, 107, 122 Glucose, 23, 107 Glycoprotein, 30, 107 Governing Board, 107, 119 Grade, 12, 59, 98, 107 Graft, 107, 108, 109 Graft Rejection, 107, 109 Granule, 43, 107 Granulocytes, 107, 111, 114, 123, 128 Growth factors, 107, 115 H Half-Life, 12, 107 Hemangiopericytoma, 55, 107 Hematopoietic Stem Cell Transplantation, 20, 107 Hematopoietic Stem Cells, 11, 107, 114 Heme, 102, 107, 119 Hemorrhage, 107, 125 Hepatic, 20, 23, 107, 119, 123 Heredity, 106, 107 Heterogeneity, 5, 93, 107 Histidine, 107, 110 Homogeneous, 15, 107 Homoharringtonine, 42, 108 Homologous, 94, 108, 121, 125 Hormone, 104, 108, 118, 120, 122, 123, 126 Host, 96, 108, 109, 127 Hybrid, 100, 108 Hydrogen, 96, 103, 108, 113, 115, 116, 120 Hydrolysis, 97, 100, 108, 117, 120 Hydroxyurea, 58, 108 Hypersensitivity, 104, 108, 122 Hypertension, 42, 108 Hypopigmentation, 24, 26, 108 Hypoxia, 16, 108 I Id, 37, 43, 82, 83, 88, 90, 108 Idiopathic, 27, 53, 108 Idiopathic myelofibrosis, 53, 108
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Immune function, 8, 108 Immune response, 8, 46, 93, 95, 107, 108, 109, 125, 127 Immune system, 95, 108, 109, 112, 114, 127, 128 Immunity, 8, 108 Immunization, 108, 109 Immunofluorescence, 4, 109 Immunology, 6, 8, 93, 106, 109 Immunophenotyping, 8, 109 Immunosuppressive, 109 Immunosuppressive therapy, 109 Immunotherapy, 11, 109 Immunotoxins, 109, 121 Impairment, 109, 113 Implant radiation, 109, 110, 121, 128 In situ, 12, 109 In vitro, 4, 7, 10, 12, 13, 15, 16, 27, 30, 41, 109, 119 In vivo, 4, 10, 12, 15, 30, 109 Incubation, 109, 111 Incubation period, 109, 111 Indicative, 109, 116, 127 Induction, 11, 13, 109, 123 Infarction, 102, 109, 113 Infection, 8, 95, 97, 99, 108, 109, 111, 112, 122, 125, 128 Inflammation, 108, 109, 122 Infusion, 9, 110 Ingestion, 95, 110 Inoperable, 18, 32, 68, 110 Inorganic, 100, 110 Insight, 9, 110 Interferon, 11, 12, 18, 22, 42, 51, 58, 59, 63, 64, 69, 110, 112 Interferon Alfa-2a, 64, 110 Interferon-alpha, 12, 18, 22, 42, 110 Internal radiation, 110, 121, 128 Interstitial, 16, 18, 27, 42, 98, 110, 122, 128 Intestinal, 62, 110 Intestine, 98, 100, 104, 108, 110, 111 Intracellular, 10, 109, 110, 123 Intravenous, 110 Intrinsic, 13, 94, 110 Invasive, 108, 110 Irinotecan, 47, 50, 110 Irradiation, 48, 110, 128 K Kb, 76, 110 Kinetic, 111 L Labile, 100, 111
Laparoscopy, 62, 111 Large Intestine, 100, 103, 110, 111, 122 Leiomyosarcoma, 7, 111 Lentivirus, 13, 111 Lethal, 4, 111 Leucocyte, 104, 111, 112 Leukaemia, 20, 22, 28, 31, 40, 111 Leukocytes, 97, 99, 107, 110, 111, 114 Leukocytosis, 111, 118 Library Services, 88, 111 Ligament, 111, 120 Lipid, 4, 111 Liver, 18, 51, 93, 96, 103, 106, 107, 111, 119 Liver metastases, 18, 111 Localized, 109, 111, 118 Loop, 15, 111 Lovastatin, 111, 123 Lymphatic, 109, 111, 112, 124 Lymphatic system, 112, 124 Lymphoblastic, 4, 46, 47, 48, 112 Lymphoblasts, 93, 112 Lymphocyte, 95, 112 Lymphocytic, 40, 61, 112 Lymphoid, 19, 51, 95, 111, 112, 114 Lymphoma, 15, 18, 112 Lymphoproliferative, 21, 112 Lysine, 110, 112 M Maculopapular, 27, 112 Malignancy, 4, 18, 112 Malignant, 4, 13, 14, 53, 54, 55, 56, 63, 93, 95, 98, 112, 114, 115, 121, 123 Malignant tumor, 98, 112, 114, 115 Mastocytosis, 63, 112 Mediate, 42, 112 MEDLINE, 77, 112 Medullary, 41, 112 Megakaryocytes, 98, 112 Melanin, 108, 112, 117, 127 Melanocytes, 108, 112 Melanoma, 12, 49, 112 Membrane, 96, 101, 103, 112, 118, 119, 123, 126 Memory, 8, 112 Meninges, 99, 112 Meningioma, 54, 55, 112 Menstrual Cycle, 113, 120 Mental Disorders, 66, 113 Mercury, 105, 113 Metabolite, 21, 24, 97, 111, 113 Metastasis, 6, 113 Metastatic, 28, 49, 53, 56, 64, 113, 123
Index 133
Metastatic cancer, 56, 113 MI, 91, 113 Microbe, 113, 126 Microbiology, 96, 113 Microorganism, 100, 113, 127 Mitochondrial Swelling, 113, 114 Mitosis, 96, 113 Modeling, 104, 113 Modification, 9, 113 Molecular, 4, 5, 6, 7, 10, 11, 14, 15, 19, 21, 25, 26, 28, 31, 36, 40, 77, 79, 97, 101, 103, 113 Molecule, 4, 5, 95, 96, 100, 101, 102, 104, 105, 106, 108, 113, 116, 118, 121, 123, 127 Monitor, 5, 114, 115 Monoclonal, 96, 109, 110, 114, 121, 128 Monocytes, 111, 114 Morphological, 22, 104, 112, 114 Multiple Myeloma, 26, 114 Myelodysplastic syndrome, 20, 114, 124 Myelofibrosis, 27, 28, 53, 114, 119 Myelogenous, 4, 11, 12, 13, 15, 18, 19, 22, 23, 24, 25, 26, 27, 29, 30, 31, 32, 41, 42, 45, 46, 47, 48, 49, 50, 51, 52, 57, 58, 59, 60, 61, 62, 64, 93, 97, 100, 114 Myeloid Cells, 114 Myeloid Progenitor Cells, 15, 114 Myelosuppression, 32, 114 Myocardium, 113, 114 N Naive, 8, 114 NCI, 1, 6, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 59, 60, 62, 64, 65, 75, 114 Necrosis, 23, 95, 109, 113, 114 Need, 5, 10, 84, 114 Needle biopsy, 62, 105, 114 Neoplasia, 114 Neoplasm, 114, 123, 127 Neoplastic, 4, 9, 11, 112, 114, 115 Nerve, 95, 103, 114, 115, 119, 124 Nervous System, 99, 114, 115, 125 Networks, 8, 115 Neural, 8, 115 Neuroblastoma, 21, 56, 115 Neurons, 43, 103, 115, 125 Neutrons, 94, 110, 115, 121 Neutrophil, 58, 115 Nuclear, 98, 104, 106, 114, 115 Nucleic acid, 23, 102, 106, 115 Nucleus, 95, 99, 102, 106, 114, 115, 120, 125 O Oligodendroglial, 115
Oligodendroglioma, 52, 54, 115 Oncogenes, 14, 115, 121 Oncogenic, 4, 13, 15, 111, 115 Open Reading Frames, 111, 115 Orbit, 105, 115, 116 Osteogenic sarcoma, 115 Osteosarcoma, 31, 42, 56, 115 Ovarian epithelial cancer, 56, 116 Ovaries, 116 Ovum, 102, 116, 120, 128 Oxidation, 97, 102, 116 P Palliative, 116, 125 Pancreas, 39, 93, 103, 116 Pancreatic, 15, 16, 39, 43, 116 Pancreatic cancer, 15, 16, 39, 43, 116 Papilla, 116 Papillary, 55, 116 Papule, 112, 116 Parietal, 116, 117, 118 Partial remission, 116, 122 Particle, 116, 126 Pathogenesis, 9, 15, 116 Pathologic, 96, 97, 102, 108, 116 Pathologic Processes, 96, 116 Pelvic, 62, 116, 120 Peptide, 4, 116, 118, 120 Perfusion, 108, 116 Periorbital, 31, 69, 116 Peripheral blood, 10, 26, 28, 107, 110, 116, 120 Peripheral stem cell transplantation, 46, 48, 116, 126 Peritoneal, 20, 56, 62, 117 Peritoneal Cavity, 56, 117 Peritoneum, 117, 122 Pharmacodynamics, 10, 117 Pharmacokinetic, 117 Pharmacologic, 95, 107, 117, 126 Phenotype, 8, 11, 117 Phenylalanine, 117, 127 Phlebotomy, 25, 117 Phospholipases, 117, 123 Phosphorus, 98, 117 Phosphorylate, 15, 117 Phosphorylation, 5, 10, 15, 41, 117, 120 Phosphotyrosine, 5, 117 Physical Examination, 58, 62, 117 Physiologic, 94, 97, 107, 113, 117, 122 Physiology, 15, 117 Pigment, 112, 118 Pilocytic, 28, 118
134
Gleevec
Placenta, 118, 120 Plants, 94, 107, 118, 124, 126 Plasma, 24, 95, 97, 114, 118, 123 Plasma cells, 95, 114, 118 Plasmid, 106, 118, 127 Platelet Activation, 118, 123 Platelet-Derived Growth Factor, 14, 26, 36, 40, 42, 118 Platelets, 58, 112, 114, 118, 125 Platinum, 62, 100, 111, 118 Pleura, 118 Pleural, 43, 118 Pleural cavity, 118 Pleural Effusion, 43, 118 Pneumonitis, 18, 27, 118 Polycythemia Vera, 25, 53, 63, 117, 118 Polymerase, 7, 30, 119 Polymerase Chain Reaction, 7, 30, 119 Polymorphism, 14, 119 Polyposis, 100, 119 Polysaccharide, 95, 119 Pons, 98, 119 Porphyria, 117, 119 Porphyria Cutanea Tarda, 117, 119 Postnatal, 119, 124 Postsynaptic, 119, 123 Potentiates, 16, 26, 40, 119 Potentiation, 119, 123 Practicability, 119, 126 Practice Guidelines, 78, 82, 119 Preclinical, 9, 120 Precursor, 104, 105, 117, 120, 127 Preleukemia, 114, 120, 124 Progesterone, 12, 120, 124 Prognostic factor, 19, 120 Progression, 5, 9, 63, 69, 95, 120 Progressive, 9, 54, 99, 104, 107, 108, 114, 118, 120, 122, 127 Progressive disease, 108, 120 Prophylaxis, 8, 120 Proportional, 106, 120 Prostate, 6, 36, 40, 120 Protein Kinases, 32, 115, 120 Protein S, 13, 97, 106, 120 Proteins, 10, 12, 94, 95, 98, 99, 100, 113, 116, 117, 118, 120, 123, 126 Protein-Tyrosine Kinase, 13, 120 Proteinuria, 114, 120 Proteolytic, 101, 120 Protocol, 49, 120 Protons, 94, 108, 120, 121 Proto-Oncogenes, 115, 121
Protozoa, 113, 121, 124 Public Policy, 77, 121 Publishing, 16, 121 Pulmonary, 58, 97, 104, 121 Pulse, 114, 121 R Radiation, 15, 48, 53, 54, 59, 105, 106, 110, 121, 126, 128 Radiation therapy, 48, 54, 59, 105, 110, 121, 126, 128 Radioactive, 107, 108, 109, 110, 115, 121, 128 Radioimmunotherapy, 15, 121 Radioisotope, 16, 121 Radiolabeled, 16, 110, 121, 128 Radiotherapy, 98, 110, 121, 128 Randomized, 11, 63, 104, 121 Reactivation, 70, 121 Receptor, 4, 8, 14, 16, 26, 36, 41, 95, 121, 123 Recombinant, 110, 122, 127 Recombination, 106, 122 Rectal, 57, 122 Rectum, 95, 98, 100, 103, 106, 111, 120, 122 Red blood cells, 105, 108, 114, 119, 122 Reductase, 111, 122, 123 Refer, 1, 100, 106, 114, 115, 121, 122 Refractory, 10, 11, 24, 25, 33, 41, 56, 61, 62, 64, 122 Regimen, 10, 59, 104, 122 Relapse, 11, 13, 19, 122 Remission, 11, 13, 17, 19, 23, 25, 28, 30, 46, 122 Renal failure, 18, 122 Resection, 18, 82, 122 Residual disease, 5, 122 Respiration, 114, 122 Response rate, 6, 68, 122 Restoration, 121, 122 Retroperitoneal, 7, 122 Rheumatism, 122 Rheumatoid, 33, 122 Rheumatoid arthritis, 33, 122 Ribonucleoside Diphosphate Reductase, 108, 122 Rod, 96, 123 S Salivary, 103, 116, 123 Salivary glands, 103, 123 Sarcoma, 26, 55, 69, 98, 123, 124 Screening, 58, 100, 123 Secondary tumor, 113, 123
Index 135
Secretion, 13, 123 Semen, 120, 123 Sequencing, 119, 123 Serum, 94, 100, 123 Side effect, 12, 58, 62, 93, 103, 114, 123, 126 Signal Transduction, 6, 9, 14, 15, 117, 123 Signs and Symptoms, 122, 123 Simvastatin, 22, 123 Skeletal, 114, 123 Small cell lung cancer, 47, 50, 124 Smoldering leukemia, 114, 124 Soft tissue, 17, 56, 82, 97, 107, 124 Soft tissue sarcoma, 17, 56, 82, 124 Solid tumor, 4, 12, 15, 49, 51, 70, 96, 103, 124 Soma, 124 Somatic, 9, 113, 124 Somatic cells, 9, 113, 124 Specialist, 83, 124 Species, 94, 96, 99, 105, 108, 111, 113, 114, 124, 127, 128 Specificity, 5, 94, 120, 124 Sperm, 99, 124 Spinal cord, 96, 98, 99, 112, 113, 115, 124 Spleen, 111, 112, 119, 124 Splenomegaly, 118, 124 Spores, 4, 124 Stem cell transplantation, 25, 40, 46, 48, 59, 107, 124 Stem Cells, 12, 28, 105, 107, 114, 116, 124 Steroid, 123, 124 Stimulus, 105, 124, 125 Stomach, 62, 64, 93, 103, 105, 106, 108, 117, 124, 125 Strand, 119, 125 Stress, 122, 125 Stroke, 66, 76, 125 Stroma, 12, 15, 41, 125 Stromal, 6, 16, 18, 20, 26, 28, 31, 32, 48, 49, 53, 63, 68, 69, 97, 125 Stromal Cells, 97, 125 Stromal tumors, 18, 20, 28, 31, 125 Subacute, 109, 125 Subclinical, 109, 125 Subcutaneous, 104, 125 Substance P, 113, 123, 125 Substrate, 5, 22, 125 Suppression, 12, 13, 22, 125 Symphysis, 120, 125 Synaptic, 123, 125 Systemic, 12, 97, 105, 109, 110, 121, 125, 128
Systolic, 108, 125 T Therapeutics, 29, 40, 125 Thermal, 115, 119, 125 Threshold, 11, 108, 125 Thrombocytes, 118, 125 Thrombosis, 120, 125 Thyroid, 21, 41, 126, 127 Tin, 118, 126 Tomography, 17, 126 Topoisomerase inhibitors, 110, 126 Total-body irradiation, 48, 126 Toxic, iv, 5, 102, 108, 109, 126 Toxicity, 4, 5, 104, 113, 126 Toxicokinetics, 126 Toxicology, 78, 126 Toxins, 95, 104, 109, 121, 126 Trachea, 126 Transcription Factors, 115, 126 Transduction, 13, 14, 123, 126 Transfection, 97, 126 Translational, 6, 27, 126 Translocation, 4, 5, 11, 13, 15, 126 Trauma, 108, 114, 126 Treatment Outcome, 20, 126 Trisomy, 32, 126 Troxacitabine, 29, 126 Tumor suppressor gene, 14, 127 Tumour, 28, 127 Tyrosine, 4, 5, 7, 10, 12, 13, 15, 20, 22, 28, 33, 36, 39, 41, 42, 43, 117, 120, 127 U Unconscious, 108, 127 Unresectable, 28, 49, 53, 64, 127 Uremia, 122, 127 Urethra, 120, 127 Urine, 21, 97, 120, 127 Uterus, 102, 111, 116, 120, 127 V Vaccine, 4, 11, 68, 93, 120, 127 Vascular, 7, 15, 21, 109, 118, 127 Vascular endothelial growth factor, 21, 127 Vector, 126, 127 Vein, 58, 110, 115, 117, 127 Venous, 120, 127 Venules, 97, 98, 127 Veterinary Medicine, 77, 127 Viral, 6, 8, 115, 121, 126, 127 Virulence, 126, 127 Virus, 12, 96, 110, 126, 127 Viscera, 124, 127
136
Gleevec
Vitro, 7, 11, 12, 15, 127 Vivo, 4, 6, 12, 15, 127 W White blood cell, 46, 58, 93, 95, 97, 100, 111, 112, 114, 115, 118, 128 Windpipe, 126, 128 X Xenograft, 95, 128
X-ray, 59, 101, 105, 106, 110, 115, 121, 128 X-ray therapy, 110, 128 Y Yeasts, 106, 117, 128 Z Zoledronate, 43, 128 Zygote, 9, 128
