TEMOZOLOMIDE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2003 by ICON Group International, Inc. Copyright ©2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Temozolomide: 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: 0-597-83942-5 1. Temozolomide-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 temozolomide. 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 TEMOZOLOMIDE ....................................................................................... 3 Overview........................................................................................................................................ 3 Federally Funded Research on Temozolomide................................................................................ 3 E-Journals: PubMed Central ....................................................................................................... 20 The National Library of Medicine: PubMed ................................................................................ 21 CHAPTER 2. NUTRITION AND TEMOZOLOMIDE ............................................................................. 53 Overview...................................................................................................................................... 53 Finding Nutrition Studies on Temozolomide .............................................................................. 53 Federal Resources on Nutrition ................................................................................................... 55 Additional Web Resources ........................................................................................................... 56 CHAPTER 3. ALTERNATIVE MEDICINE AND TEMOZOLOMIDE ....................................................... 57 Overview...................................................................................................................................... 57 National Center for Complementary and Alternative Medicine.................................................. 57 Additional Web Resources ........................................................................................................... 64 General References ....................................................................................................................... 64 CHAPTER 4. CLINICAL TRIALS AND TEMOZOLOMIDE .................................................................... 65 Overview...................................................................................................................................... 65 Recent Trials on Temozolomide ................................................................................................... 65 Keeping Current on Clinical Trials ............................................................................................. 79 CHAPTER 5. PATENTS ON TEMOZOLOMIDE .................................................................................... 81 Overview...................................................................................................................................... 81 Patents on Temozolomide............................................................................................................. 81 Patent Applications on Temozolomide......................................................................................... 86 Keeping Current .......................................................................................................................... 89 CHAPTER 6. PERIODICALS AND NEWS ON TEMOZOLOMIDE .......................................................... 91 Overview...................................................................................................................................... 91 News Services and Press Releases................................................................................................ 91 Academic Periodicals covering Temozolomide............................................................................. 93 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................... 95 Overview...................................................................................................................................... 95 U.S. Pharmacopeia....................................................................................................................... 95 Commercial Databases ................................................................................................................. 96 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 99 Overview...................................................................................................................................... 99 NIH Guidelines............................................................................................................................ 99 NIH Databases........................................................................................................................... 101 Other Commercial Databases..................................................................................................... 103 APPENDIX B. PATIENT RESOURCES ............................................................................................... 105 Overview.................................................................................................................................... 105 Patient Guideline Sources.......................................................................................................... 105 Finding Associations.................................................................................................................. 107 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 109 Overview.................................................................................................................................... 109 Preparation................................................................................................................................. 109 Finding a Local Medical Library................................................................................................ 109 Medical Libraries in the U.S. and Canada ................................................................................. 109 ONLINE GLOSSARIES................................................................................................................ 115 Online Dictionary Directories ................................................................................................... 115
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TEMOZOLOMIDE DICTIONARY ............................................................................................ 117 INDEX .............................................................................................................................................. 155
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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 temozolomide 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 temozolomide, 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 temozolomide, 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 temozolomide. 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 temozolomide, 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 temozolomide. 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 TEMOZOLOMIDE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on temozolomide.
Federally Funded Research on Temozolomide The U.S. Government supports a variety of research studies relating to temozolomide. 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 temozolomide. 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 temozolomide. The following is typical of the type of information found when searching the CRISP database for temozolomide: •
Project Title: AGT DEPLETION FOR THERAPY OF CNS TUMORS Principal Investigator & Institution: Quinn, Jennifer A.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: The prognosis of patients with malignant glioma remains dismal, with conventional treatment with surgery, radiotherapy and alkylnitrosourea-based
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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chemotherapy failing to cure all patients with glioblastoma multiforme and the majority of patients with anaplastic astrocytoma. This failure is due almost exclusively to de novo or acquired resistance to chemotherapy with subsequent tumor growth and patient death. The nitrosoureas and methylators such as procarbazine were originally chosen for treatment of central nervous system tumors on the basis of favorable physiochemical properties such as lipophilicity as well as activity against L1210 leukemia cells growing intracranially in mice. Nevertheless, despite moderate sensitivity to malignant glioma to BCNU or lomustine, the nitrosoureas have not dramatically altered survival for patients with malignant brain tumors. This situation presumably reflects de novo or acquired intrinsic cellular resistance rather than restricted delivery to the intracranial site. The major mechanism of resistance to alkylnitrosourea and methylator therapy is the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT). AGT removes chlorethylation or methylation damage from the O6-position of guanine prior to cell injury and death. The high incidence of AGT activity in human central nervous system tumors, as well as the inverse relationship between procarbazine activity and alkyltransferase levels in human brain tumor xenografts, supported a role for this protein in mediating resistance to nitrosoureas in patients with CNS tumors and provided an approach for reversal of drug resistance. Furthermore three recent clinical trials have suggested that AGT levels in patients receiving BCNU therapy correlate with outcome. The hypothesis of this proposal are 1) AGT plays a critical role in mediating resistance of malignant glioma to nitrosoureas and methylators and 2) O6benzylguanine (O6-BG) mediated reduction of glioma AGT levels can enhance nitrosourea (BCNU) and methylator (temozolomide) treatment of these tumors. The specific aims of this proposal are 1) to further define the toxicity of BCNU + O6- BG and temozolomide + O6-BG respectively, in the treatment of adults with malignant glioma; 2) to define the activity and subsequently efficacy of BCNU +06-BG and temozolomide and O6-BG respectively, in the treatment of adults with malignant glioma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMBATING ALKYLATING AGENT RESISTANCE IN HUMAN GLIOMAS Principal Investigator & Institution: Silber, John R.; Neurological Surgery; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 28-FEB-2003 Summary: (As Adapted From the Investigator's Abstract): Malignant gliomas have an extremely poor prognosis with median survival rates of less than 2 years. Although most frequent in older adults, these malignancies are the third leading cause of cancer deaths in persons 15 to 34 years of age. Moreover, the incidence of malignant gliomas is increasing in those older than 65. Alkylating agents, when used in single agent or combination chemotherapy along with surgery and radiation, are the most effective antitumor drugs for the treatment of adult gliomas. However, intrinsic and acquired resistance to alkylating agents limits their usefulness. The broad, long-term objective is to define the contribution of DNA repair mechanisms to glioma resistance to chemotherapeutic agents (methylating and chloroethylating agents), and to identify strategies to combat resistance. The applicants have shown that resistance of 9 human glioma cell lines to alkylating agents is based on a mechanism(s) in addition to the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). Their hypothesis is that the 3-methyladenine-DNA glycosylase (3-MAG), an enzyme which initiates base excision repair of n3-methyladenine and other N-alkylpurines, also contributes to resistance. To confirm this hypothesis, they will demonstrate that N3-methyladenine,
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the principal substrate of 3-MAG, is lethal to human glioma cells by correlating adduct removal with sensitivity to MeOSO2(CH2)2-lexitropsin, a recently developed alkylator that methylates almost exclusively at the N3 atom of adenine. They will also use antisense mRNA expression to suppress 3-MAG in previously analyzed glioma lines in which we have quantitated alkylating agent cytotoxicity and the contribution of MGMT to resistance. They will quantitate the effect of antisense expression on 3-MAG mRNA and enzyme levels, and on chloroethylating and methylating agent cytotoxicity in the absence and presence of O6-benzylguanine, a substrate analog inhibitor of MGMT. In related work, they will quantitate 3-MAG, together with MGMT, in newly diagnosed and recurrent brain tumors, and asses the relationship of enzyme levels to response to alkylating agent therapy. The tissue studies, together with the in vitro work, will aid them in identifying potentially effective alkylating agent/inhibitor therapies. If their hypothesis is correct, inhibitors of 3-MAG might eventually be tested clinically, either with or without concurrent inhibition of MGMT with O6-benzylguanine. It is a logical expectation that a combination of differentially targeted inhibitors might effectively potentiate alkylating agent chemotherapy for adult gliomas. This is a revised application. The long-term goals of the project are to define the contribution of DNA repair mechanisms to glioma resistance to alkylating chemotherapeutic agents. Three specific aims are outlined to test the hypothesis that 3-methyladenine DNA glycosylase, the enzyme that initiates base excision repair at N3-meAd and other N-alkyl purines, contributes to alkylating agent resistance. Specific aim 1 will attempt to establish that unrepaired N3-meAd DNA adducts are toxic to human glioma cells. Specific aim 2 will determine whether modulation of 3-MAG levels affects sensitivity to methylating and chloroethylating agents. Specific aim 3 will measure the levels of 3-MAG and MGMT in newly diagnosed and recurrent brain tumors. In an effort to define the role of 3-MAG in clinical drug resistance, enzyme levels will be correlated with response to alkylator adjuvant therapy and clinical course. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CWRU/UHICC PHASE I TRIALS OF ANTICANCER AGENTS Principal Investigator & Institution: Remick, Scot C.; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-MAR-1994; Project End 31-JAN-2003 Summary: (Applicant's Description) The primary focus of the Developmental Therapeutics Program at Case Western Reserve University (CWRU)/University Hospitals Ireland Cancer Center (UHICC) has been to incorporate both pharmacokinetic and pharmacodynamic clinically assessable endpoints on which to base therapeutic intervention in all phase I clinical trials. It is anticipated that with more rational administration of cytotoxic chemotherapy that is mechanistically based the therapeutic ratio will be enhanced. For the p a s t several years, an interactive and multi-disciplinary team of investigators at our institution has effectively and creatively designed a variety of phase I clinical studies. Which are mechanistically-based. Recent efforts have explored the biochemical modulation of enzymes involved in DNA damage and repair metabolism, including principally, O-alkylguanine DNA alkyltransferase (AGT) and topoisomerase I. It is the intent of this application to continue to build on this strong clinical translational research theme and, more importantly, to provide a resource for the cooperative evaluation of scientifically directed phase I trials of anti-cancer agents in collaboration with the CTEP. Four areas of active interest have been identified by our program for phase I drug development as part of this cooperative agreement: 1) develop therapeutic regimens based on the biochemical modulation of the DNA repair enzyme
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(AGT) using a variety of agents including O benzylguanine (OBG), BCNU, temozolomide, and SarCNU; 2) i n i t i ate the first clinical trials of the photosensitizer silicon phthalocyanine Pc 4 - photodynamic therapy (PDT), a compound discovered at our institution; 3) translate promising strategies based in laboratory programs involving poly (ADP-ribose) polymerase (PARP) and NAD depletion, modulation of alkylating agent sensitivity by glucose-regulated protein GRP78, and topisomerase I into clinical trials; and finally 4) continue to employ the strategy of pharmacokinetic and pharmacodynamic-guided correlative studies in the evaluation of new agents that become available for study during the course of this cooperative agreement. A unique and important component of these studies is to continue to obtain sequential visceral CT-guided tumor biopsies for translational laboratory correlative studies. The identification, design, and prioritization of phase I studies for new agents will be based on laboratory evaluation in preclinical models conducted at the CWRU/UHICC and developed in collaboration with CTEP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LEUKEMIAS
DNA
REPAIR
IN
PROTECTING
AGAINST
SECONDARY
Principal Investigator & Institution: Dolan, M Eileen.; Associate Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-APR-2003 Summary: The DNA repair protein, O6-alkylguanine-DNA alkyltransferase (AGT) has been shown to protect cells from the toxic effects of alkylating agents including chloroethylnitrosoureas, methylating agents and cyclophosphamide. Most primary tumors have high AGT activity which is primarily responsible for the limited usefulness of these drugs. Severe myelosuppression and therapy-induced myeloid leukemia are life-threatening side effects encountered with the clinical use of alkylating agents. The activity of the AGT protein in human hematopoietic progenitors is very low and it is reasonable to suggest that this is the basis of their high sensitivity to the myelotoxic and mutagenic effects of alkylating agents. In efforts to increase the therapeutic efficacy of alkylnitrosoureas, we have developed O6-benzylguanine (BG). This compound is a potent, selective inactivator of the AGT repair protein that is presently in phase I/II clinical trials as a modulator of alkylating agents. While combining BG with alkylating agents increases killing of a variety of tumor cells, a major concern is that BG will impair the ability of immature hematopoietic cells to repair alkylator-induced damage and that this will, in turn, result in an increase in the incidence of secondary leukemias. In support of this, preliminary data from our phase I trial of BG and BCNU indicates myelosuppression as the dose limiting toxicity. The subject of this proposal is to determine whether BG increases the mutagenicity of alkylating agents which may contribute to the induction of secondary leukemias and more importantly, to use this information to generate therapies to protect against this devastating side effect. Specific aim 1 will address whether inhibition AGT activity results in an increase in mutation frequency at the Hprt locus by cyclophosphamide, BCNU and temozolomide using an in vitro and in vivo model. We will establish whether cells expressing BG-resistant AGT proteins will be protected from BG plus alkylating agent-induced mutations. Specific aim 2 will directly address the question of whether the use of BG with alkylating agents will increase the incidence of therapy related leukemias. Heterozygous Nf1 knockout mice provide an excellent in vivo model of cyclophosphamide-induced myeloid leukemia. Specific aim 3 and 4 describe approaches to combat this devastating side effect. We will generate lines of transgenic mice that over-express mutant AGT to cross
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with Nf1 mice to determine if there is protection against the incidence of leukemias. In the last specific aim we are proposing the introduction of mutant alkyltransferase genes into hematopoietic stem cells. The introduction of stem cells containing mutant agt genes with high dose alkylating agent chemotherapy will allow us to decrease tumor burden and improve upon the duration of disease free survival and decrease the likelihood of secondary leukemias. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: E2F-1 CANCER GENE THERAPY Principal Investigator & Institution: Mcmasters, Kelly M.; Surgery; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2006 Summary: (PROVIDED BY APPLICANT): The major reason for the failure of anticancer drug therapy in most advanced solid tumors is the presence of chemotherapy-resistant tumor cells. Apoptosis is now considered to be an essential event in antitumor drug induced death. Therefore, cells with deficient apoptotic pathways may be incapable of producing an efficient apoptotic response, regardless of the agent to which they are exposed. For this reason, gene therapy using proapoptotic genes that can either trigger apoptosis in chemo-resistant cells or reconstitute the apoptotic pathway to enhance chemotherapy is a potential therapeutic strategy. The transcription factor, E2F-1, has recently been identified as a potent tumor suppressor. We and others have shown that E2F- 1 overexpression efficiently induces apoptosis in a variety of tumor types, independent of p53 status, both in vitro and in vivo. However, the mechanisms by which E2F-1 induces apoptosis remain ill defined. Mechanistically, our preliminary data implicate activation of the Fas death receptor pathway, involving ASK1, JNK, p38, and ERK MAP kinases in E2F- 1-mediated apoptosis, a novel finding. Furthermore, NFkappaB activation and downregulation of inhibitors of apoptosis (IAPs, specifically XIAP and cIAP-1) and the antiapoptotic Bcl-2 family member, Mcl-1 were seen after E2F-1- overexpression, again novel findings. Furthermore, our preliminary studies indicate that topoisomerase I and II agents, and the drug temozolomide work cooperatively with E2F-1 to induce apoptosis in colon cancer and melanoma cells in vitro and in vivo. Based on substantial preliminary data and the existing literature, we have proposed a model of the signal transduction pathways involved in E2F-1-mediated apoptosis. To evaluate this model and further dissect the molecular mechanisms of E2F1-induced apoptosis, SK-MEL-2 melanoma and HT-29 colon cancer cells will be studied. Following adenovirus-mediated gene transfer we will analyze the role of Fas/FasL interaction, JNK, p38, and ERK activation, NFKB activation, and XIAP, cIAP-1 and Mcl-1 in E2F-1-mediated apoptosis. Investigation will also be carried out using combinations of adenovirus E2F-1 and specific chemotheraeutic agents that act cooperatively with E2F-1 (adriamycin. camptothecin, temozolomide) to evaluate the mechanisms by which E2F-1 augments the apoptotic response to chemotherapy. Finally, a novel adenoviral vector expressing a truncated E2F-1 mutant that maintains apoptotic function but lacks E2F-1 transactivation function will be constructed and tested for potential enhancement of tumor death. These studies will enhance our understanding of E2F-1-mediated cell death and facilitate the design of improved treatment strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENZYMES AND REACTIONS FOR REPAIR OF DNA IN HUMAN CELLS Principal Investigator & Institution: Brent, Thomas P.; Member; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2001; Project Start 01-AUG-1977; Project End 30-JUN-2004 Summary: PROVIDED BY APPLICANT) Human MGMT protects cells against lethality and mutagenicity of intrinsic and environmental DNA damage by removing adducts from O(6)-guanine and thus is a critical determinant of response to anticancer chloroethylating (e.g. BCNU), and methylating (e.g. temozolomide) drugs, as well as their potential carcinogenicity. Because normal tissues and tumors exhibit a wide spectrum of MGMT expression, while the gene is completely silenced in a subset of tumor, we wish to understand the mechanisms for regulation of MGMT. Having earlier characterized the 5' promoter region of the gene, demonstrating a tight correlation between methylation of "hotspots" within the 5' -CpG island and MGMT silencing, we now hypothesize (Aim 1) that a methylated CpG-binding protein (e.g. MeCP2) binds the methylated region, followed by recruitment of histone deacetylase (HDAC), whose activity leads to local chromatin compaction and exclusion of transcription factors. We shall test this model by determining the acetylation status of histones H3 and H4 located at the MGMT promoter, in expressing versus silenced cells. We shall examine the effect on histone acetylation and MGMT expression, of inhibiting HDAC with Trichostatin A, or inhibiting methylation with 5 -azadeoxycytidine. Based on our observation that the MGMT 5'enhancer binding protein (MEBP) is excluded from the nucleus of MGMT silenced cells, we now propose to address the hypothesis that MGMT expression requires the MEBP to be localized to the nucleus. We shall initially isolate, identify and characterize the protein (Aim 2) enabling us to generate antibodies with which to monitor MEBP intracellular localization and determine correlation with MGMT expression levels. 3, to isolate the cDNA for MEBP will enable us to generate probes with which to explore MEBP function by modulating its expression, initially in reporter gene studies. Ultimately, armed with the molecular tools for monitoring and modulating promoter methylation and histone-acetylation, as well as MEBP expression and localization, we shall be able to explore the interrelationships between all these parameters. The long-term goal is to test the hypothesis, that MEBP enhancer binding is a primary event in MGMT expression, while methylation and deacetylation at the promoter represent secondary events that stabilize the silenced gene state. If nuclear localization of MEBP is indeed a primary event, regulation of its localization would become a primary focus for future studies. Elucidation of these factors involved in regulation of MGMT expression may provide new markers for susceptibility to environmental carcinogens or of potential resistance to cancer chemotherapy, and may suggest new interventions in these processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMPROVED OPHTHALMIC CARE FOR RETINOBLASTOMA PATIENTS Principal Investigator & Institution: O'brien, Joan M.; Director; Ophthalmology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The long-term objective of this proposal is to improve ophthalmic care for patients with a pediatric ocular tumor, retinoblastoma (RB). We propose to provide rapid diagnosis and improved prognosis for patients with
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heritable ocular RB through improved genetic testing, and to innovate more effective and less toxic therapies for this ophthalmic disease.In pursuit of these objectives, two specific aims are proposed. These are: I. To develop and validate a protein truncation test (PTT) for detection of germline retinoblastoma gene (RB1) mutations and to determine whether mutation analysis can be used to predict ocular disease expression.This aim will be accomplished in 3 stages. We propose to: A. Develop PTT. B. Perform focused DNA sequencing to characterize RB1 mutations detected by PTT. C. Determine whether mutation analysis can be used to predict ocular disease expression.II. To determine the potential clinical utility of selected new pharmacologic agents in RB. These are: A. Cyclosporin A, and two potential alternatives, PSC-833 and FK506. B. Retinoids, including all-trans retinoic acid, ALRT1550, AM80, fenretinide, Targretin, 9-cis retinoic acid, and 13-cis retinoic acid.C. The alkylating agent, temozolomide. D. The blood-brain barrier permeabilizer, RMP-7 (Cereport).E. The tumor-specific viral agents, ONYX-015 and ONYX-RB1.These agents are chosen for their relatively low toxicity and potential efficacy in the management of this ocular tumor. These agents also have potential utility in the management of other ophthalmic disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IN UTERO GENE THERAPY TO FETAL HEMATOPOIETIC STEM CELLS Principal Investigator & Institution: Mahler, Wendy R.; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): The goal of this proposal is to use in utero gene delivery to target highly proliferative hematopoietic stem cells (HSC) in the fetal liver. Current limitations to successful gene therapy for hematopoietic disorders include low efficiency of transduction of long term repopulating cells, gene silencing in transduced clones of cells, and the lack of a selective advantage to allow preferential growth and expansion of the transgene. Targeting HSC populations from the mid-gestation fetal liver, at a time when the cells are rapidly expanding, has the potential to transduce large numbers of HSC. This group and others have been successful at in utero gene transfer. We will enrich for transduced cells by applying postnatal selection for the presence of a specific methylguanine methyltransferase (P140K MGMT) included in gene transfer vectors. Finally, we will use this approach to transduce and select HSC expressing P140K MGMT and human a globin in a murine model of beta thalassemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ION CHANNELS AND TRANSPORTERS AS GLIOMA-SPECIFIC TARGETS Principal Investigator & Institution: Sontheimer, Harald W.; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-MAY-2007 Summary: One of the major impediments for the successful treatment of malignant glioma is the unusual ability of glioma cells to disseminate by invasion into healthy brain. Much research effort has focused on understanding the mechanisms underlying cell motility and the cells' interactions with the extracellular matrix environment. Comparatively little, however, is known concerning intrinsic adaptations of glioma cells, which may facilitate cell invasion. Based on our recent findings, we hypothesize that the
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movement of ions through ion channels and ion transporters aid the growth and dissemination of glioma cells. We suggest that glioma cells show up-regulation of certain C1- and K+ channels not found in normal glia which allow them to rapidly adjust their cell shape and cell volume thereby facilitating cell invasion. Importantly, these channels allow for the secretion of KCI along with water. The resulting cycle of cell shrinkage and subsequent restoration of cell volume enables cells to navigate the tortuous extracellular spaces in brain. In addition, we hypothesize that glioma cells utilizes a cystine-glutamate transporter that releases neurotoxic glutamate to actively kill peritumoral tissue and provide room for tumor growth. In this proposal, we have developed 3 testable hypotheses, which seek to delineate the specific contribution of ion channels and ion transporters to glioma cell invasion and tumor growth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MGMT-MEDIATED IN VIVO SELECTION IN A LARGE ANIMAL MODEL Principal Investigator & Institution: Kiem, Hans-Peter; Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Genetic modification of hematopoietic stem cells to provide chemoprotection and allow for in vivo selection has tremendous potential for the treatment of malignant and nonmalignant diseases. Unfortunately, stem cell gene therapy and in vivo selection strategies developed in the mouse have generally not been predictive for outcomes in large animal or human studies. Thus, we propose to study in vivo selection strategies in the dog, a well-established clinically relevant large animal model for stem cell gene therapy and transplantation. We propose to use O6benzylguanine (BG) resistant mutants of O6-methylguanine-DNA methyltransferase (MGMT) as selectable drug-resistance genes in combination with BCNU and temozolomide. Our first objective is to determine the optimal vector and MGMT mutant for efficient chemoprotection and selection of MGMT-transduced cells in the autologous transplant setting. Results from these studies will be directly relevant for ongoing stem cell gene therapy protocols in patients with genetic diseases and for patients with malignant diseases receiving chemotherapy with BCNU or temozolomide. The second object of this application is to extend in vivo selection strategies to the nonmyeloablative allogeneic transplantation setting. Clinical studies have shown that high-dose chemotherapy is not required for engraftment of allogeneic stem cells, and nonmyeloablative transplantations are now being performed for many malignant and nonmalignant diseases. However, graft rejection, relapse, and GVHD have remained significant problems after nonmyeloablative transplantation. Here we hypothesize that gene-modified, chemoprotected allogeneic stem cells can be used to a) permit safer and less toxic administration of post-transplant chemotherapy in the setting of persistent or recurrent disease and b) facilitate engraftment of allogeneic stem cells after nonmyeloablative transplantation. Our preliminary data indicate that the dog is an excellent preclinical model to study the feasibility of combining stem cell gene therapy with nonmyeloablative transplantation, two highly powerful treatment strategies. These experiments will provide a platform for studies using gene-modified allogeneic stem cells to improve nonmyeloablative transplant strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MODULATING BASE EXCISION REPAIR IN TUMOR DRUG RESISTANCE Principal Investigator & Institution: Gerson, Stanton L.; Professor of Medicine; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Applicant's Abstract) Alkylating agents remain the backbone of chemotherapy for many malignant tumors. Well-defined mechanisms of alkylating agent resistance prevent optimal therapeutic response. The applicant proposes to investigate the methylating class of chemotherapeutic agents and to study the resistance to these agents mediated by base excision repair (BER). In the past, studies of methylating agent resistance have focused on two DNA repair processes, 06alkylguanine DNA alkyltransferase and mismatch repair. However, the bulk of DNA adducts formed by methylating agents such as temozolomide are repaired by base excision repair. The applicant's preliminary data suggest that inhibition of base excision repair provides a novel approach to overcoming tumor resistance to methylating agents, especially in cells, which express high AGT and/or have defects in MMR resulting in profound methylating agent resistance. On this basis, the specific aims of this application are: 1) to determine whether human tumor cell lines with various DNA repair defects in p53, AGT and MMR express similar levels of BER proteins, 2) to optimize inhibition of BER by the AP site binding agent, methoxyamine (MX) in vitro and study its potentiation of temozolomide (TMZ) cytotoxicity, 3) to characterize the nature of the cytotoxic killing due to MX mediated interruption of BER by measurement of cell cycle arrest, apoptosis and chromosomal aberrations, and 4) to establish optimal conditions for MX enhancement of TMZ anticancer efficacy in xenograft bearing nude mice. These studies are designed to identify BER as a new target for biochemical modulation of tumor drug resistance that can become a focus of anti-cancer drug development leading to therapeutic clinical trials with these or related agents. By targeting a defined mechanism of drug resistance to a well-understood class of compounds, it should be possible to enhance the therapeutic index of methylating agents and improve anticancer responses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOUNT SINAI COMMUNITY CLINICAL ONCOLOGY PROGRAM Principal Investigator & Institution: Lilenbaum, Rogerio C.; Mount Sinai Medical Center (Miami Beach) 4300 Alton Rd Miami Beach, Fl 331402800 Timing: Fiscal Year 2002; Project Start 13-JUL-1987; Project End 31-MAY-2007 Summary: (provided by applicant): Over the next five years, the overall aim of the CCOP is to reduce cancer incidence, morbidity, and mortality by accelerating the transfer of newly developed cancer prevention, early detection, treatment, patient management, rehabilitation, and continuing care technology to widespread community application. The immediate goals of the MSCCOP are to continue to increase our accrual rate to treatment and cancer control trials approved by NCI; to increase our ascending minority accrual in treatment and cancer control research; to maintain standards of excellence in data management; to cultivate contacts with primary care physicians and other specialists who may contribute to cancer control initiatives; to continue to refine cancer control data management capabilities, including the use of a range of resources to identify potential candidates for cancer control research projects; and to continue to develop our affiliate network of 7 clinical research sites in 5 cities. The track record of the MSCCOP demonstrates the ability to manage complex clinical research and cancer
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control activities while producing the highest quality data. The CCOP staffing pattern, protocol management procedures, patient/participant management approaches, quality control mechanisms, pharmacy control mechanisms, IRB structure and liaison are all in place and functioning to support current and future therapeutic and cancer control activities. The Mount Sinai Community Clinical Oncology Program provides access to national cooperative clinical trials to South Florida. The 6 hospitals in the MSCCOP see nearly 7000 newly diagnosed cancer patients per year, including rapidly rising minority and elderly populations. The MSCCOP brings together the strength and resources of a strong group of investigators who collaborate in the conduct of studies from CALGB, NSABP, RTOG, and the H. Lee Moffitt Cancer Center. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MR PHARMACOANGIOGRAPHY-VASCULAR MODULATION OF DELIVERY Principal Investigator & Institution: Artemov, Dmitri Y.; Assistant Professor; Radiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Although chemotherapy remains a major course of cancer treatment, it frequently fails to provide a complete cure for solid tumors. Several mechanisms contribute to this failure. Many established chemotherapeutic agents have significant antiangiogenic activity, which may reduce drug delivery during the course of a cycle of therapy. The vascular damage inflicted by the previous cycle(s) of therapy, is therefore a critically important determinant of tumor drug resistance in vivo. With our recently developed NMR techniques we can detect the delivery and spatial distribution of 13C labeled drugs in orthotopic tumors using 13C magnetic resonance techniques. We have also established that the delivery and spatial distribution of a low molecular weight contrast agent such as GdDTPA correlates well with the delivery and spatial distribution of the differentiating agent phenylbutyrate. Therefore we can now assess the efficiency of drug delivery during the course of chemotherapy in a preclinical model of human breast cancer, and evaluate the potential benefits of modulating tumor vascularization to improve tumor response to therapy with the same model genetically modified to overexpress VEGF. Our goals in this application are as follows. (i) To develop a clinically translatable surrogate marker for drug delivery by comparing tumor uptake and distribution of the carbon-13 labeled anticancer drug temozolomide and the clinically approved contrast agent GdDTPA. (ii) To determine the effect of a cycle of temozolomide chemotherapy on vascular characteristics and drug delivery. (iii) To evaluate effects of increased angiogenic capacity of tumors, genetically engineered to overexpress VEGF, on drug delivery, development of physiologic drug resistance, and treatment outcome. If successful, a clinically applicable surrogate marker would be of utmost importance for predicting effective drug delivery. Such a surrogate marker can also be used to follow strategies of improving tumor vascular delivery of chemotherapeutic agents. The experimental designs in this application will also, for the first time, evaluate the role of antivascular effects of a chemotherapeutic agent in tumor resistance using noninvasive and spatially informative techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MS/AL RADIATION ONCOLOGY RESEARCH PARTNERSHIP Principal Investigator & Institution: Wynn, Raymond B.; Singing River Hospital System 2809 Denny Ave Pascagoula, Ms 39567
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Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant) The Mississippi/Alabama Radiation Oncology Research Partnership is formed to establish and sustain a radiation oncology research program that will address cancer disparities among African Americans and underserved populations in the Mississippi region. The potential partners include the Regional Cancer Center (RCC) at Singing River Hospital System (SRHS) in Pascagoula, Mississippi, the University of Alabama Comprehensive Cancer Center (UABCCC) in Birmingham, Alabama, and the Gulf Coast Minority-Based Cooperative Clinical Oncology Program (MBCCOP). The overall goal of the proposed partnership is to improve access and accrual of cancer clinical trials for African American and historically underserved populations. Clinical trials are the principal tools for achieving and demonstrating progress in cancer treatment and prevention. Unfortunately, the level of accrual of African Americans and underserved populations in clinical trials is disproportionate to the disease burden. In addition, many health care institutions that provide care to a disproportionate number of these populations are not often linked to the national cancer research protocols. As a result, radiation oncologists in these institutions have a difficult time starting, developing, and sustaining research programs. Thus, this proposed partnership seeks funding to support the planning, development, and implementation of a radiation oncology clinical trials program. Three pilot clinical trials research projects will be conducted as part of implementation of the research program to address patient accrual. Project #1 is the "Intensity Modulated Radiotherapy for Head and Neck Cancer." Project #2 is "Phase II study of Gamma Knife Radiosurgery and Temozolomide (Temodar) for Newly Diagnosed Brain Metastases." Project #3 is "Evaluation of Prostate Screening Outcomes in African American Men." The proposed research plan will enable investigators to examine whether increasing access to cancer clinical research trials will increase accrual and participation. The partnership collaboration will serve as the major vehicle for building a research infrastructure and generating new findings in radiation oncology that may impact cancer disparities in African American and underserved populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NABTC MEMBER INSTITUTION GRANT Principal Investigator & Institution: Fink, Karen L.; Neurology; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2001; Project Start 30-MAR-1994; Project End 31-DEC-2002 Summary: (Applicant's Description) This application is the University of Texas Southwestern Medical Center (UTSW) proposal to continue participation in Phase I and 11 investigational drug trials in adults with anaplastic gliomas in a multi-institutional consortium, the North American Brain Tumor Consortium (NABTC). The ultimate purpose of this consortium is to identify agents and regimens with sufficient activity to justify definitive Phase III testing. In general, these Phase III trials will be conducted in larger groups in which the NABTC member institutions may participate. With this application, the NABTC is being reorganized and combined with another central nervous system tumor consortium, the NCNSC, to improve efficiency and accelerate accrual. Data management and statistical support for the consortium studies are being transferred to M.D. Anderson Hospital. The Contra Operations Office of the NABTC will continue to be the University of California at San Francisco. In three years, the NABTC has accrued 165 patients to four studies, including one completed protocol (9401) and three protocols nearing completion (9402, 9403, and 9404). Two LOI's for new protocols have been approved (9701 and 9702). The study coordinator for three of these
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six protocols (9404, 9701, and 9702) is the PI on this application. These and subsequent trials will include pharmacokinetic studies, which will continue to be performed at the University of Texas at San Antonio, and tissue banking for biological studies. Agents or regimens to be tested in subsequent Phase I and 11 trials of the NABTC will be selected during semiannual consortium meetings and will be based on: a) CTEP recommendations and preferences, b) pre-clinical experimental data from p a rticipant consortium institutions, and c) knowledge of the current literature with frequent interchanges about prioritizing potential new regimens. The newly reorganized NABTC estimates accrual of 60-80+ patients per year from the seven institutions that will be enrolling patients. This should allow completion of three to four trials per year, and pharmacokinetic (or other biologic) studies will be conducted on most, if not all, of these trials. UTSW participants in these consortium trials have been and will continue to be a multi-disciplinary team of neuro-oncologists, neurosurgeons, pediatric oncologists, radiation oncologists, and neuropathologists. UTSW is the only brain tumor research center in the north-central Texas region, and approximately 65 patients are enrolled on formal brain tumor protocols annually. With reorganization of the NABTC, we anticipate that a significant percentage of these will be enrolled on NABTC studies, which will be given highest priority within the institution. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NABTC MEMBER INSTITUTION GRANT (UCSF PROJECT LEADER) Principal Investigator & Institution: Lieberman, Frank S.; Neurological Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 18-MAR-1994; Project End 31-DEC-2003 Summary: (Applicant's Description) Malignant brain tumors are highly lethal cancers. Despite considerable efforts at improving treatment through advances in neurosurgical technique, neuroimaging, radiotherapy, and chemotherapy, the overall prognosis of patients with malignant brain tumors remains grim. To improve outcome, coordinated clinical research is required to evaluate promising new treatment approaches. Laboratory studies of basic brain tumor biology are needed to develop more effective and better tolerated therapeutic strategies. The North American Brain Tumor Consortium (NABTC) was established four years ago for the broad purpose of stimulating cooperative efforts among multidisciplinary teams of clinical and laboratory researchers to improve treatment for patients with brain tumors. To accomplish the long term goal of developing more effective therapies for patients with brain tumors, we specifically propose to: 1. Share expertise with brain tumor clinicians and researchers in multiple disciplines. 2. Conduct joint Phase I and 11 clinical trials for patients with brain tumors, providing adequate patient populations for their timely completion. 3. Share brain tumor specimens and data that will be useful in the conduct of clinical pharmacologic and correlative laboratory studies. This proposal describes the neurooncology activities at the University of Pittsburgh, and reviews the resources available through the University of Pittsburgh Cancer Institute (UPCI), an NCI-designated Comprehensive Cancer Center, and the University of Pittsburgh Medical Center (UPMC), qualifying it for continuing participation in the North American Brain Tumor Consortium. The Central Operations Office/Coordinating Center for the NABTC will remain at the University of California, San Francisco. The UPCI and UPMC will provide essential support for all NABTC-related trials through such facilities as the General Clinical Research Center, the Clinical Core Facility, and the Tumor Tissue Bank. The University of Pittsburgh will collaborate with other members of the NABTC to rapidly evaluate new treatments by enrolling patients in Phase I and 11 NABTC clinical trials
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and to develop promising new therapeutic strategies through translational laboratory studies of brain tumor specimens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NMR DETECTION OF 13C-TEMOZOLOMIDE IN CANINE BRAIN TUMORS Principal Investigator & Institution: Mancuso, Anthony D.; Research Professor; Radiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 13-SEP-2000; Project End 31-AUG-2003 Summary: (Adapted from applicant's abstract): The purpose of the proposed study is to determine the feasibility of monitoring the pharmacokinetics of a 13C-labeled drug [313C]temozolomide (TMZ) by NMR spectroscopy in a large animal model at clinical dose levels. Studies will be performed on transplantable gliomas in adult beagles and in dogs with spontaneous brain tumors. Preliminary studies have already demonstrated the feasibility of monitoring [3-13C]TMZ by selective 13C polarization transfer spectroscopy in mice with subcutaneous RIF-1 tumors at 9.4 after administration of doses that were 25 times the clinical dose of 200 mg/m2 (5.91 mg/kg). The proposed study will determine the feasibility of undertaking clinical trials of this method in human subjects. Temozolomide is currently in Phase II clinical trials and has shown promising activity against human brain tumors and melanomas. The proposed study employs temozolomide as a prototype to test the general concept of using 13C-labeling of antineoplastic agents as a method for monitoring their pharmacokinetics by NMR spectroscopy. This method would facilitate tailor-fitting of chemotherapy schedules to the needs of individual patients and reliably identifying nonresponsive patients at an early stage of chemotherapy, thereby sparing them unnecessary toxicity and expense. The first objective of this project is to determine the optimum method for detecting [313CJTMZ. Four methods will be evaluated on phantoms and on dogs with transplantable gliomas on a 4.7T/50 cm animal spectrometer: 1) selective polarization transfer from 1H to 13C with detection of 13C, 6 2) inverse polarization transfer from 13C to 1H with detection of 1H, 42 3) gradient echo heteronuclear multiple quantum coherence transfer from 13C to 1H with detection of 1H, 4 4) proton observe carbon decouple spectroscpy.5 These methods will be compared with respect to sensitivity, power deposition and motion sensitivity. The method chosen on the basis of these studies will be implemented on clinical 1.5 T and 4T scanners and used to monitor the pharmacokinetics of [3-13C]TMZ in dogs with transplantable gliomas and spontaneous brain tumors. The labeled drug will be synthesized by the applicants, who have developed a more efficient and economical method of synthesis of [3-13C]TMZ than had been reported in the literatue.33 Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHASE I & II STUDIES IN CHILDREN WITH SOLID TUMORS Principal Investigator & Institution: Santana, Victor M.; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2002; Project Start 06-SEP-2002; Project End 30-JUN-2003 Summary: (provided by applicant): Although contemporary treatment strategies have improved the survival of children with solid tumors, relapse or refractory disease still accounts for the leading cause of death in these children. New therapeutic strategies are needed and a further understanding of the biologic and biochemical processes that control tumor proliferation, differentiation and cell death to provide insights into how
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promising new chemotherapeutic and biologic agents can be incorporated into treatment regimens. This Project 10 comprises the clinical Phase I/II research studies of this Program Project Grant and focuses on 3 hypotheses: (1) that the rapamycin analogue CCI-779 will inhibit the signal transduction molecule mTOR (target of rapamycin) and retard the growth of pediatric tumors; (2) that an inhibitor of ErbB1 signaling (ZD1839) in combination with intravenous camptothecins will produce clinically meaningful responses in children with neuroblastoma and highgrade gliomas either through direct inhibition of ErbB1 in tumors expressing this receptor (glioblastomas) or through modulating ABC transporters such as BCRP and MRP in neuroblastoma; and (3) that 4-anilinoquinazolones such as ZD1839 may modulate the bioavailability of oral camptothecins and result in systemic exposures associated with response in pre-clinical xenograft models. Incorporated into selected clinical trials will be assessments of the expression of the ErbB family of receptors and BCRP/MRP, and mTOR inhibition and recovery. Each clinical trial is derived from observations in laboratory projects. Specific aim 1 focuses on evaluation of CCI-779 as a single agent or in combination defining toxicity, potential activity and markers of tumor response. In Specific aims 2 and 3, we will evaluate oral ZD1839 in combination with intravenous or oral camptothecins defining the MTD, bioavailability and tumor responses. Lastly, Specific aim 4 will focus on continued evaluation of a pharmacokinetically targeted approach to dosing of topotecan for relapsed Wilms tumor and combination studies of camptothecins with DNA damaging agents. This clinical project is fundamental in translating key laboratory discoveries into the treatment approaches for children with solid tumors, and providing direction for continued laboratory investigations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHASE I CLINICAL TRIALS OF ANTICANCER AGENTS Principal Investigator & Institution: Ratain, Mark J.; Professor of Medicine and Chairman; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2001; Project Start 10-MAY-1995; Project End 28-FEB-2003 Summary: (Applicant's Description) The overall objective of this proposal is to conduct phase I and pharmacological studies of new anticancer agents. These studies will aim to define the recommended phase II dose, toxicities, pharmacokinetics, and pharmacodynamics of such agents. Some of these trials may incorporate pharmacokinetics or pharmacodynamic modulators. Five new s t udies are proposed. These include 1)evaluation of genotyping for abnormalities in the UGT*1.1 promoters region (known to cause Gilbert's syndrome) and phenotyping with buprenorphine (a known substrate for UGI*1.1) a s p o t e ntial predictors of CPT-11 toxicity (diarrhea) and SN-38 glucuronidation (known to be a substrate for UGT*1.1); 2) evaluation of [O]6benzylguanine (BG) pharmacodynamics in patients with colorectal cancer or sarcoma undergoing surgical resections; 3)evaluation of BG in combination with temozolomide; 4)evaluation of ketoconazole (a potent inhibitor of CYP3A4 on carboxyanidoimadzole (a substrate for CYP3A4) pharmacokinetics and toxicity; and 5)evaluation of UCN-01 on biweekly (24 hr infusion) schedule. All studies will include both pharmacokinetics and correlative laboratory studies. The project total accrual is 375 patients, or 75 patients per year. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHASE I OF BCNU AND TEMOZOLOMIDE Principal Investigator & Institution: Hammond, Lisa; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229
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Timing: Fiscal Year 2001 Summary: This is a phase I and pharmacokinetic study of increasing dose combination of BCNU (carmustine, a standard alkylating agent) and Temozolomide (an investigational alkylating agent). The maximum tolerated dose, the dose limiting toxicities, pharmacokinetics, and effects of the combination on ATase activity will be determined. The study has been extended to accomodate further patient accrual. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHASE I/II PK/PD STUDIES OF AGENTS FOR CNS MALIGNANCIES Principal Investigator & Institution: Kuhn, John G.; Professor; Pharmacology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2001; Project Start 28-MAR-1994; Project End 31-DEC-2002 Summary: (Applicant's Description) For the proposed work, it is our intent as part of the North American Brain Tumor Consortium (NABTC) to derive pharmacological information on selected anticancer agents in Phase I/II clinical trials for the treatment of CNS malignancies. The drugs to be studied and the extent of each study will be determined by the Program Leader (Michael Prados, M.D. UCSF-Lead Institution). For a pharmacokinetic study, the work will consist of two phases: (a) Development or implementation of a suitable analytical methodology for the measurement of likely tissue and biological fluids. Specifically, HPLC or GC methodologies will be established for quantitation of the compound (such as taxol & temozolomide) being studied. Development of appropriate methodologies may require determination of physicochemical properties such as solubilities, binding of drug to plasma proteins and stability of the drugs in various matrixes at various temperatures. This phase must be successfully completed b e f o r e entering into the next phase. (b) Characterization of the pharmacokinetics/pharmacodynamics of the agent under going clinical evaluation will include: maximum plasma or CSF concentration; plasma or CSF clearance; apparent volume of distribution at steady state; area under the plasma (CSF) time curve; tissue or CSF distribution and harmonic mean plasma/CSF half-lives. Attempts will be made to correlate these pharmacokinetic parameters with the observed biological effects such as toxicity and/or response data. Generally these studies will be confined to the parent drug. However, in instances where extensive metabolism occurs, the development of analytical methodology for measurement of the metabolites will be pursued so that parallel pharmacokinetic/pharmacodynamic determinations of these compounds can be conducted along with the parent compound. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHASE II STUDY OF TEMOZOLOMIDE (SCH52365) PRIOR TO RADIATION THERAPY Principal Investigator & Institution: Agarwala, Sanjiv; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001 Summary: This is a multinational, multicenter, open label Phase II study designed to determine the efficacy and safety of Temozolomide (SCH 52365) in the treatment of patients who have brain metastases from malignant melanoma not requiring immediate radiation therapy, previously untreated for this presentation of brain metastases, except for steroids, & who may or may not have received previous chemotherapy for the treatment of malignant melanoma. It is anticipated that 10 patients will enter this study at the University of Pittsburgh Cancer Institute.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHASE II TRIAL OF TEMOZOLOMIDE & BCNU FOR MALIGNANT GLIOMAS Principal Investigator & Institution: Prados, Michael D.; Professor; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001 Summary: This study endeavors to determine the safety and efficacy of these two noted chemotherapy agents when administered in combination with each other. Thus, we will be assessing toxicity as well as response to treatment or time of progression-free survival, depending on the histology of the patient. GCRC expertise with clinical trials will be helpful with the following study procedures: (1) administration and documentation that study medications were received at the proper doses and with the correct timing relative to each other, and (2) consistant and thorough assessment and monitoring of toxicity while patient is receiving drug. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGIONAL AGT DEPELTION OF CNS AND LEPTOMENINGEAL TUMORS Principal Investigator & Institution: Friedman, Henry S.; Professor; Pediatrics; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2005 Summary: (provided by applicant) Central nervous system (CNS) neoplasms which either arise in the brain or metastasize from an extraneural primary site, are highly malignant tumors refractory to all conventional therapy. Similarly, patients with neoplastic meningitis from virtually any tumor such as melanoma, sarcoma or breast carcinoma do poorly, with mean survival following leptomeningeal spread measured in months. The major impediment to successful treatment is de novo or acquired resistance to chemotherapy. Temozolomide is an imidazole tetrazinone similar to dacarbazine, requiring conversion to the active methylating agent MTIC. Methylating agents, including temozolomide, produce cytotoxicity due to a lethal cycle of mismatch repair following cellular misrecognition of O(6)-methylguanine. Recent preclinical and clinical studies have confirmed the activity of temoxolomide in the treatment of malignant glioma. Unfortunately, the majority of patients ultimately display resistance to temozolomide. The two primary mechanisms of resistance to temozolomide and other alkylating agents are the enzyme O(6)-alkylguanine-DNA alkyltransferase (AGT) and a deficiency in the DNA mismatch repair pathway. Of these two mechanisms, AGT plays a primary role in resistance to temozolomide by removing the alkyl groups from the O(6) position of guanine, in effect reversing the cytotoxic lesion of temozolomide. The sensitivity of tumor cell lines to temozolomide and the alkylating agent BCNU can be correlated with AGT levels. Regional therapy of CNS parenchymal or leptomeningeal neoplasms with intratumoral or intrathecal administration respectively, offers the potential benefit of enhancing delivery to the target neoplasm while minimizing delivery and hence toxicity to systemic organs. We have previously demonstrated the activity and modest toxicity of intrathecal temozolomide in the treatment of athymic rats bearing subarachnoid AGT-human malignant gliom xenografts. We have extended these results and demonstrated the activity and safety of temozolomide delivered by intracerebral microinfusion in the treatment of malignant gliomas intracranially in athymic nude rats. The specific aims of this proposal are: 1. To define the role of
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intratumoral O(6)-BG and other AGT inhibitors in enhancing systemic or intratumoral temozolomide therapy of malignant glioma; 2. To define the role of intrathecal AGT inhibitors in enhancing system or intrathecal temozolomide therapy of neoplastic meningitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ST.LOUIS-CAPE GIRARDEAU CCOP Principal Investigator & Institution: Henry, Patrick H.; Chairman; St.Louis-Cape Girardeau Ccop 12800 Corporate Hill Dr St. Louis, Mo 63131 Timing: Fiscal Year 2002; Project Start 01-JUN-1987; Project End 31-MAY-2007 Summary: (provided by applicant): The St. Louis-Cape Girardeau CCOP is a consortium of four hospitals in two separate bi-state health service areas serving parts of eastern Missouri and western Illinois. The Investigators from the St. Louis Metropolitan area are affiliated with one or both of the two hospitals in the consortium and have worked together for the past eighteen years in cancer treatment research protocols and more recently, in cancer control research studies. The Cape Girardeau Investigators have worked with CCOP for the past nine years and are affiliated with two hospitals in that city. During the next five years we expect to accrue at least sixty credits per year for cancer treatment research protocols of the NSABP and SWOG and at least seventy five credits (new participants and follow-up) per year for cancer control and prevention studies. These cancer control credits will be derived primarily from our participation in the Breast Cancer Prevention Trial-1, Prostate Cancer Prevention Trial-1 and the Breast Cancer Prevention Trial-2. We will continue to provide high quality data to the Southwest Oncology Group and the National Surgical Adjuvant Breast and Bowel Project which are our research bases, utilizing the data management system developed during the past eighteen years. In summary, we will continue our excellent performance of the past eighteen years in cancer treatment research studies and extend our more recent participation in cancer control and prevention trials. The past experience and capabilities of the Investigators and Clinical Research Associates provides a strong base for continuing development of this Community Clinical Oncology Program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TELOMERASE SPECIFIC CASPASE TRANSFER FOR GLIOMAS Principal Investigator & Institution: Kondo, Seiji; Neurosurgery; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2005 Summary: (provided by applicant): Our efforts to treat malignant gliomas are focused on methods to transfer the caspase genes to tumors. Because the apoptotic pathway may be disrupted in tumors and caspases are the mainstay of apoptosis programs, this approach is one of the most promising strategies for cancer gene therapy. However, if caspases were transduced to normal brain cells, they will undergo apoptosis. To restrict induction of apoptosis to tumor cells, we need to establish a tumor specific expression system of caspases. Telomerase is a particularly attractive target for the tumor-targeting system. It is because a vast majority of malignant gliomas have telomerase activity, while most normal brain cells do not. Activation of telomerase is tightly regulated at the transcriptional level of the telomerase catalytic subunit (hTERT). Therefore, we hypothesize that by using the hTERT promoter-driven vector system, the expression of caspases can be restricted to telomerase-positive malignant gliomas. In preliminary studies, we constructed the caspase-8 (initiator caspase) or rev-caspase-6 (executioner
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caspase) expression vector with the hTERT promoter (hTERT/caspase-8 or rev-caspase6) and demonstrated that each construct induced apoptosis in telomerase-positive malignant glioma cells, but not in cultured astrocytes lacking telomerase. Furthermore, the growth of subcutaneous tumors in nude mice was significantly suppressed by the treatment with the hTERT/rev-caspase-6. Additionally, the antitumor effect of hTERT/caspase-8 or rev-caspase-6 was enhanced by the combination with anticancer drug, cisplatin. The goal of this proposal is to investigate whether treatment with the hTERT/caspase-8 or rev-caspase-6 construct is an effective approach for telomerasepositive malignant gliomas using an experimental model of human malignant gliomas. The specific aims are: 1) to select tumor model systems for the in vivo treatment with hTERT/caspase-8 or rev-caspase-6 construct, 2) to investigate the antitumor effect of the hTERT/caspase-8 or rev-caspase-6 construct on intracranial tumors, 3) to investigate their in vitro and in vivo antitumor efficacy combined with conventional therapy (cisplatin, temozolomide, or gamma-irradiation), and 4) to investigate the molecular mechanisms underlying the effect of the hTERT/caspase-8 or rev-caspase-6. A unique focus of this work is the emphasis on the telomerase-specific gene transfer of caspases. We anticipate that the studies described in the current proposal will lead to a novel and promising targeting approach for malignant gliomas expressing telomerase activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TEMOZOLOMIDE & BCNU FOR ANAPLASTIC GLIOMAS Principal Investigator & Institution: Greenberg, Harry S.; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRIAL OF TEMOZOLOMIDE IN CHILDREN AND ADOLESCENTS WITH PROGRESSIVE CANCER Principal Investigator & Institution: Matthay, Katherine K.; Professor; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 31-MAR-2002 Summary: This abstract is not available. 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
3 4
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.
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unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “temozolomide” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for temozolomide in the PubMed Central database: •
Tolerance of human MSH2 +/[minus sign] lymphoblastoid cells to the methylating agent temozolomide. by Marra G, D'Atri S, Corti C, Bonmassar L, Cattaruzza MS, Schweizer P, Heinimann K, Bartosova Z, Nystrom-Lahti M, Jiricny J.; 2001 Jun 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34640
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 temozolomide, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “temozolomide” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for temozolomide (hyperlinks lead to article summaries): •
3-aminobenzamide and/or O6-benzylguanine evaluated as an adjuvant to temozolomide or BCNU treatment in cell lines of variable mismatch repair status and O6-alkylguanine-DNA alkyltransferase activity. Author(s): Wedge SR, Porteous JK, Newlands ES. Source: British Journal of Cancer. 1996 October; 74(7): 1030-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8855970&dopt=Abstract
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A mechanistic mathematical model of temozolomide myelosuppression in children with high-grade gliomas. Author(s): Panetta JC, Kirstein MN, Gajjar AJ, Nair G, Fouladi M, Stewart CF. Source: Mathematical Biosciences. 2003 November; 186(1): 29-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14527745&dopt=Abstract
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. 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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A Phase I and pharmacokinetic study of temozolomide and cisplatin in patients with advanced solid malignancies. Author(s): Britten CD, Rowinsky EK, Baker SD, Agarwala SS, Eckardt JR, Barrington R, Diab SG, Hammond LA, Johnson T, Villalona-Calero M, Fraass U, Statkevich P, Von Hoff DD, Eckhardt SG. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1999 July; 5(7): 1629-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10430061&dopt=Abstract
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A phase I trial of 1,3-bis(2-chloroethyl)-1-nitrosourea plus temozolomide: a North American Brain Tumor Consortium study. Author(s): Schold SC Jr, Kuhn JG, Chang SM, Bosik ME, Robins HI, Mehta MP, Spence AM, Fulton D, Fink KL, Prados MD. Source: Neuro-Oncology. 2000 January; 2(1): 34-9. Erratum In: Neuro-Oncol 2001 April; 3(2): 123. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11302252&dopt=Abstract
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A phase II EORTC study of temozolomide in patients with malignant pleural mesothelioma. Author(s): van Meerbeeck JP, Baas P, Debruyne C, Smit EF, van Klaveren RJ, Galdermans D, Lentz MA, Manegold C, Giaccone G; EORTC Lung Cancer Group. Source: European Journal of Cancer (Oxford, England : 1990). 2002 April; 38(6): 779-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11937311&dopt=Abstract
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A phase II pilot trial of concurrent biochemotherapy with cisplatin, vinblastine, temozolomide, interleukin 2, and IFN-alpha 2B in patients with metastatic melanoma. Author(s): Atkins MB, Gollob JA, Sosman JA, McDermott DF, Tutin L, Sorokin P, Parker RA, Mier JW. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 October; 8(10): 3075-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374674&dopt=Abstract
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A phase II study of extended low-dose temozolomide in recurrent malignant gliomas. Author(s): Khan RB, Raizer JJ, Malkin MG, Bazylewicz KA, Abrey LE. Source: Neuro-Oncology. 2002 January; 4(1): 39-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772431&dopt=Abstract
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A phase II study of temozolomide in advanced untreated pancreatic cancer. Author(s): Moore MJ, Feld R, Hedley D, Oza A, Siu LL. Source: Investigational New Drugs. 1998; 16(1): 77-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9740547&dopt=Abstract
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A phase II study of temozolomide in hormone-refractory prostate cancer. Author(s): van Brussel JP, Busstra MB, Lang MS, Catsburg T, Schroder FH, Mickisch GH. Source: Cancer Chemotherapy and Pharmacology. 2000; 45(6): 509-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10854140&dopt=Abstract
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A phase II study of temozolomide in patients with newly diagnosed supratentorial malignant glioma before radiation therapy. Author(s): Gilbert MR, Friedman HS, Kuttesch JF, Prados MD, Olson JJ, Reaman GH, Zaknoen SL. Source: Neuro-Oncology. 2002 October; 4(4): 261-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356356&dopt=Abstract
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A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Author(s): Yung WK, Albright RE, Olson J, Fredericks R, Fink K, Prados MD, Brada M, Spence A, Hohl RJ, Shapiro W, Glantz M, Greenberg H, Selker RG, Vick NA, Rampling R, Friedman H, Phillips P, Bruner J, Yue N, Osoba D, Zaknoen S, Levin VA. Source: British Journal of Cancer. 2000 September; 83(5): 588-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10944597&dopt=Abstract
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A phase II trial of oral temozolomide in patients with metastatic renal cell cancer. Author(s): Park DK, Ryan CW, Dolan ME, Vogelzang NJ, Stadler WM. Source: Cancer Chemotherapy and Pharmacology. 2002 August; 50(2): 160-2. Epub 2002 July 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172983&dopt=Abstract
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A phase II trial of temozolomide for patients with recurrent or progressive brain metastases. Author(s): Abrey LE, Olson JD, Raizer JJ, Mack M, Rodavitch A, Boutros DY, Malkin MG. Source: Journal of Neuro-Oncology. 2001 July; 53(3): 259-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11718258&dopt=Abstract
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A phase II trial of temozolomide in patients with unresectable or metastatic soft tissue sarcoma. Author(s): Talbot SM, Keohan ML, Hesdorffer M, Orrico R, Bagiella E, Troxel AB, Taub RN. Source: Cancer. 2003 November 1; 98(9): 1942-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14584078&dopt=Abstract
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A rapid and systematic review of the effectiveness of temozolomide for the treatment of recurrent malignant glioma. Author(s): Dinnes J, Cave C, Huang S, Milne R. Source: British Journal of Cancer. 2002 February 12; 86(4): 501-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870527&dopt=Abstract
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Abrogation of the Chk1-mediated G(2) checkpoint pathway potentiates temozolomide-induced toxicity in a p53-independent manner in human glioblastoma cells. Author(s): Hirose Y, Berger MS, Pieper RO. Source: Cancer Research. 2001 August 1; 61(15): 5843-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11479224&dopt=Abstract
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Absorption, metabolism, and excretion of 14C-temozolomide following oral administration to patients with advanced cancer. Author(s): Baker SD, Wirth M, Statkevich P, Reidenberg P, Alton K, Sartorius SE, Dugan M, Cutler D, Batra V, Grochow LB, Donehower RC, Rowinsky EK. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1999 February; 5(2): 309-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10037179&dopt=Abstract
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Activity of temozolomide against human tumor colony-forming units. Author(s): Raymond E, Izbicka E, Soda H, Gerson SL, Dugan M, Von Hoff DD. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1997 October; 3(10): 1769-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9815562&dopt=Abstract
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Activity of temozolomide in the treatment of central nervous system tumor xenografts. Author(s): Friedman HS, Dolan ME, Pegg AE, Marcelli S, Keir S, Catino JJ, Bigner DD, Schold SC Jr. Source: Cancer Research. 1995 July 1; 55(13): 2853-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7796412&dopt=Abstract
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Adenovirally-mediated transfer of E2F-1 potentiates chemosensitivity of human glioma cells to temozolomide and BCNU. Author(s): Gomez-Manzano C, Lemoine MG, Hu M, He J, Mitlianga P, Liu TJ, Yung AW, Fueyo J, Groves MD. Source: International Journal of Oncology. 2001 August; 19(2): 359-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11445852&dopt=Abstract
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An Australian experience with temozolomide for the treatment of recurrent high grade gliomas. Author(s): Harris MT, Rosenthal MA, Ashley DL, Cher L. Source: Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. 2001 July; 8(4): 325-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11437571&dopt=Abstract
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Antitumor imidazotetrazines. 41. Conjugation of the antitumor agents mitozolomide and temozolomide to peptides and lexitropsins bearing DNA major and minor groove-binding structural motifs. Author(s): Arrowsmith J, Jennings SA, Clark AS, Stevens MF. Source: Journal of Medicinal Chemistry. 2002 December 5; 45(25): 5458-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12459014&dopt=Abstract
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Antitumour imidazotetrazines XXVIII 3-methyladenine DNA glycosylase activity in cell lines sensitive and resistant to temozolomide. Author(s): Deans B, Tisdale MJ. Source: Cancer Letters. 1992 April 15; 63(2): 151-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1562991&dopt=Abstract
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Attenuation of O(6)-methylguanine-DNA methyltransferase activity and mRNA levels by cisplatin and temozolomide in jurkat cells. Author(s): D'Atri S, Graziani G, Lacal PM, Nistico V, Gilberti S, Faraoni I, Watson AJ, Bonmassar E, Margison GP. Source: The Journal of Pharmacology and Experimental Therapeutics. 2000 August; 294(2): 664-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10900246&dopt=Abstract
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Biochemical changes associated with a multidrug-resistant phenotype of a human glioma cell line with temozolomide-acquired resistance. Author(s): Ma J, Murphy M, O'Dwyer PJ, Berman E, Reed K, Gallo JM. Source: Biochemical Pharmacology. 2002 April 1; 63(7): 1219-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11960598&dopt=Abstract
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Biochemical correlates of temozolomide sensitivity in pediatric solid tumor xenograft models. Author(s): Middlemas DS, Stewart CF, Kirstein MN, Poquette C, Friedman HS, Houghton PJ, Brent TP. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 March; 6(3): 998-1007. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10741727&dopt=Abstract
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Cancer Research Campaign phase II trial of temozolomide in metastatic melanoma. Author(s): Bleehen NM, Newlands ES, Lee SM, Thatcher N, Selby P, Calvert AH, Rustin GJ, Brampton M, Stevens MF. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1995 April; 13(4): 910-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7707118&dopt=Abstract
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Case report: a patient with primary CNS lymphoma treated with temozolomide to complete response. Author(s): Lerro KA, Lacy J. Source: Journal of Neuro-Oncology. 2002 September; 59(2): 165-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12241110&dopt=Abstract
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Characterisation of urinary metabolites of temozolomide in humans and mice and evaluation of their cytotoxicity. Author(s): Tsang LL, Farmer PB, Gescher A, Slack JA. Source: Cancer Chemotherapy and Pharmacology. 1990; 26(6): 429-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2225314&dopt=Abstract
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Chemotherapy in the treatment of recurrent glioblastoma multiforme: ifosfamide versus temozolomide. Author(s): Paulsen F, Hoffmann W, Becker G, Belka C, Weinmann M, Classen J, Kortmann RD, Bamberg M. Source: Journal of Cancer Research and Clinical Oncology. 1999 July; 125(7): 411-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10394962&dopt=Abstract
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Combined effects of adenovirus-mediated wild-type p53 transduction, temozolomide and poly (ADP-ribose) polymerase inhibitor in mismatch repair deficient and nonproliferating tumor cells. Author(s): Tentori L, Portarena I, Bonmassar E, Graziani G. Source: Cell Death and Differentiation. 2001 May; 8(5): 457-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11423906&dopt=Abstract
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Combined effects of temozolomide and the ribonucleotide reductase inhibitors didox and trimidox in malignant brain tumor cells. Author(s): Figul M, Soling A, Dong HJ, Chou TC, Rainov NG. Source: Cancer Chemotherapy and Pharmacology. 2003 July; 52(1): 41-6. Epub 2003 April 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690517&dopt=Abstract
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Combined radiotherapy and temozolomide in patients with recurrent high grade glioma. Author(s): Schonekaes K, Mucke R, Panke J, Rama B, Wagner W. Source: Tumori. 2002 January-February; 88(1): 28-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12004846&dopt=Abstract
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Concomitant radiotherapy and metronomic temozolomide in pediatric high-risk brain tumors. Author(s): Sterba J, Pavelka Z, Slampa P. Source: Neoplasma. 2002; 49(2): 117-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088104&dopt=Abstract
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Current and future developments in the use of temozolomide for the treatment of brain tumours. Author(s): Stupp R, Gander M, Leyvraz S, Newlands E. Source: The Lancet Oncology. 2001 September; 2(9): 552-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11905710&dopt=Abstract
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Delayed repletion of O6-methylguanine-DNA methyltransferase resulting in failure to protect the human glioblastoma cell line SF767 from temozolomide-induced cytotoxicity. Author(s): Hirose Y, Kreklau EL, Erickson LC, Berger MS, Pieper RO. Source: Journal of Neurosurgery. 2003 March; 98(3): 591-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650433&dopt=Abstract
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Depletion of O6-alkylguanine-DNA alkyltransferase correlates with potentiation of temozolomide and CCNU toxicity in human tumour cells. Author(s): Baer JC, Freeman AA, Newlands ES, Watson AJ, Rafferty JA, Margison GP. Source: British Journal of Cancer. 1993 June; 67(6): 1299-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8512814&dopt=Abstract
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Determination of temozolomide in human plasma and urine by high-performance liquid chromatography after solid-phase extraction. Author(s): Shen F, Decosterd LA, Gander M, Leyvraz S, Biollax J, Lejeune F. Source: Journal of Chromatography. B, Biomedical Applications. 1995 May 19; 667(2): 291-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7663702&dopt=Abstract
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DNA repair enzymes and cytotoxic effects of temozolomide: comparative studies between tumor cells and normal cells of the immune system. Author(s): Pagani E, Pepponi R, Fuggetta MP, Prete SP, Turriziani M, Bonmassar L, Lacal PM, Falcinelli S, Passarelli F, Guadagni F, Alvino E, D'Atri S. Source: Journal of Chemotherapy (Florence, Italy). 2003 April; 15(2): 173-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797396&dopt=Abstract
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Effect of gastric pH on the relative oral bioavailability and pharmacokinetics of temozolomide. Author(s): Beale P, Judson I, Moore S, Statkevich P, Marco A, Cutler DL, Reidenberg P, Brada M. Source: Cancer Chemotherapy and Pharmacology. 1999; 44(5): 389-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10501912&dopt=Abstract
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Effect of O6-(4-bromothenyl)guanine on different temozolomide schedules in a human melanoma xenograft model. Author(s): Middleton MR, Thatcher N, McMurry TB, McElhinney RS, Donnelly DJ, Margison GP. Source: International Journal of Cancer. Journal International Du Cancer. 2002 August 10; 100(5): 615-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124813&dopt=Abstract
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Effect of single and multiple administration of an O6-benzylguanine/temozolomide combination: an evaluation in a human melanoma xenograft model. Author(s): Wedge SR, Porteous JK, Newlands ES. Source: Cancer Chemotherapy and Pharmacology. 1997; 40(3): 266-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9219512&dopt=Abstract
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Effect of temozolomide and dacarbazine on O6-alkylguanine-DNA alkyltransferase activity and sensitivity of human tumor cells and xenografts to 1,3-bis(2-chloroethyl)1-nitrosourea. Author(s): Mitchell RB, Dolan ME. Source: Cancer Chemotherapy and Pharmacology. 1993; 32(1): 59-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8462125&dopt=Abstract
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Effect of temozolomide on central nervous system relapse in patients with advanced melanoma. Author(s): Paul MJ, Summers Y, Calvert AH, Rustin G, Brampton MH, Thatcher N, Middleton MR. Source: Melanoma Research. 2002 April; 12(2): 175-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11930115&dopt=Abstract
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Effects of single or split exposure of leukemic cells to temozolomide, combined with poly(ADP-ribose) polymerase inhibitors on cell growth, chromosomal aberrations and base excision repair components. Author(s): Tentori L, Portarena I, Vernole P, De Fabritiis P, Madaio R, Balduzzi A, Roy R, Bonmassar E, Graziani G. Source: Cancer Chemotherapy and Pharmacology. 2001 April; 47(4): 361-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11345654&dopt=Abstract
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Effects of temozolomide in malignant brain tumours. Author(s): Osoba D. Source: Lancet. 2000 July 22; 356(9226): 342. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11071219&dopt=Abstract
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Evaluation of temozolomide in a SCID mouse model of human B-cell precursor leukemia. Author(s): Messinger Y, Reaman GH, Ek O, Uckun FM. Source: Leukemia & Lymphoma. 1999 April; 33(3-4): 289-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10221508&dopt=Abstract
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Exceptional sensitivity of testicular germ cell tumour cell lines to the new anti-cancer agent, temozolomide. Author(s): Pera MF, Koberle B, Masters JR. Source: British Journal of Cancer. 1995 May; 71(5): 904-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7734313&dopt=Abstract
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First-line therapy with temozolomide induces regression of primary CNS lymphoma. Author(s): Herrlinger U, Kuker W, Platten M, Dichgans J, Weller M. Source: Neurology. 2002 May 28; 58(10): 1573-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034807&dopt=Abstract
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Four-hourly scheduling of temozolomide improves tumour growth delay but not therapeutic index in A375M melanoma xenografts. Author(s): Middleton MR, Kelly J, Goodger S, Thatcher N, Margison GP. Source: Cancer Chemotherapy and Pharmacology. 2000; 45(1): 15-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10647496&dopt=Abstract
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From triazines and triazenes to temozolomide. Author(s): Stevens MF, Newlands ES. Source: European Journal of Cancer (Oxford, England : 1990). 1993; 29A(7): 1045-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8499135&dopt=Abstract
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Future directions for temozolomide therapy. Author(s): Yung WK. Source: Seminars in Oncology. 2001 August; 28(4 Suppl 13): 43-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550138&dopt=Abstract
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Future directions in the treatment of malignant gliomas with temozolomide. Author(s): Prados MD. Source: Seminars in Oncology. 2000 June; 27(3 Suppl 6): 41-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10866349&dopt=Abstract
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Health-related quality of life in patients treated with temozolomide versus procarbazine for recurrent glioblastoma multiforme. Author(s): Osoba D, Brada M, Yung WK, Prados M. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2000 April; 18(7): 1481-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10735896&dopt=Abstract
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Health-related quality of life in patients with anaplastic astrocytoma during treatment with temozolomide. Author(s): Osoba D, Brada M, Yung WK, Prados MD. Source: European Journal of Cancer (Oxford, England : 1990). 2000 September; 36(14): 1788-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10974627&dopt=Abstract
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Hemorrhagic cystitis as an unexpected adverse reaction to temozolomide: case report. Author(s): Islam R, Isaacson BJ, Zickerman PM, Ratanawong C, Tipping SJ. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2002 October; 25(5): 513-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393995&dopt=Abstract
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High-performance liquid chromatographic analysis and stability of anti-tumor agent temozolomide in human plasma. Author(s): Kim H, Likhari P, Parker D, Statkevich P, Marco A, Lin CC, Nomeir AA. Source: Journal of Pharmaceutical and Biomedical Analysis. 2001 January; 24(3): 461-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11199225&dopt=Abstract
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High-performance liquid chromatographic determination and stability of 5-(3methyltriazen-1-yl)-imidazo-4-carboximide, the biologically active product of the antitumor agent temozolomide, in human plasma. Author(s): Kim HK, Lin CC, Parker D, Veals J, Lim J, Likhari P, Statkevich P, Marco A, Nomeir AA. Source: J Chromatogr B Biomed Sci Appl. 1997 December 5; 703(1-2): 225-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9448080&dopt=Abstract
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Impact of chromosome 1p status in response of oligodendroglioma to temozolomide: preliminary results. Author(s): Chahlavi A, Kanner A, Peereboom D, Staugaitis SM, Elson P, Barnett G. Source: Journal of Neuro-Oncology. 2003 February; 61(3): 267-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12675321&dopt=Abstract
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In vitro evaluation of temozolomide combined with X-irradiation. Author(s): Wedge SR, Porteous JK, Glaser MG, Marcus K, Newlands ES. Source: Anti-Cancer Drugs. 1997 January; 8(1): 92-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9147618&dopt=Abstract
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Inactivation of O6-alkylguanine-DNA alkyltransferase in human peripheral blood mononuclear cells by temozolomide. Author(s): Lee SM, Thatcher N, Crowther D, Margison GP. Source: British Journal of Cancer. 1994 March; 69(3): 452-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8123472&dopt=Abstract
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Inhibition of O6-alkylguanine DNA-alkyltransferase or poly(ADP-ribose) polymerase increases susceptibility of leukemic cells to apoptosis induced by temozolomide. Author(s): Tentori L, Orlando L, Lacal PM, Benincasa E, Faraoni I, Bonmassar E, D'Atri S, Graziani G. Source: Molecular Pharmacology. 1997 August; 52(2): 249-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9271347&dopt=Abstract
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Inhibition of telomerase activity in malignant glioma cells correlates with their sensitivity to temozolomide. Author(s): Kanzawa T, Germano IM, Kondo Y, Ito H, Kyo S, Kondo S. Source: British Journal of Cancer. 2003 September 1; 89(5): 922-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12942127&dopt=Abstract
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Inhibition of telomerase increases resistance of melanoma cells to temozolomide, but not to temozolomide combined with poly (adp-ribose) polymerase inhibitor. Author(s): Tentori L, Portarena I, Barbarino M, Balduzzi A, Levati L, Vergati M, Biroccio A, Gold B, Lombardi ML, Graziani G. Source: Molecular Pharmacology. 2003 January; 63(1): 192-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488552&dopt=Abstract
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Involvement of the mismatch repair system in temozolomide-induced apoptosis. Author(s): D'Atri S, Tentori L, Lacal PM, Graziani G, Pagani E, Benincasa E, Zambruno G, Bonmassar E, Jiricny J. Source: Molecular Pharmacology. 1998 August; 54(2): 334-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9687575&dopt=Abstract
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Macrophage inflammatory protein 1alpha attenuates the toxic effects of temozolomide in human bone marrow granulocyte-macrophage colony-forming cells. Author(s): Clemons M, Watson A, Howell A, Chang J, Heyworth C, Lord B, Testa N, Dexter TM, Margison G. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 March; 6(3): 966-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10741722&dopt=Abstract
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Marked inactivation of O6-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules. Author(s): Tolcher AW, Gerson SL, Denis L, Geyer C, Hammond LA, Patnaik A, Goetz AD, Schwartz G, Edwards T, Reyderman L, Statkevich P, Cutler DL, Rowinsky EK. Source: British Journal of Cancer. 2003 April 7; 88(7): 1004-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671695&dopt=Abstract
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Metabolic activation of temozolomide measured in vivo using positron emission tomography. Author(s): Saleem A, Brown GD, Brady F, Aboagye EO, Osman S, Luthra SK, Ranicar AS, Brock CS, Stevens MF, Newlands E, Jones T, Price P. Source: Cancer Research. 2003 May 15; 63(10): 2409-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750260&dopt=Abstract
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Methoxyamine potentiates DNA single strand breaks and double strand breaks induced by temozolomide in colon cancer cells. Author(s): Taverna P, Liu L, Hwang HS, Hanson AJ, Kinsella TJ, Gerson SL. Source: Mutation Research. 2001 May 10; 485(4): 269-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11585361&dopt=Abstract
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Mismatch repair mutations override alkyltransferase in conferring resistance to temozolomide but not to 1,3-bis(2-chloroethyl)nitrosourea. Author(s): Liu L, Markowitz S, Gerson SL. Source: Cancer Research. 1996 December 1; 56(23): 5375-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8968088&dopt=Abstract
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Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group. Author(s): Yung WK, Prados MD, Yaya-Tur R, Rosenfeld SS, Brada M, Friedman HS, Albright R, Olson J, Chang SM, O'Neill AM, Friedman AH, Bruner J, Yue N, Dugan M, Zaknoen S, Levin VA. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1999 September; 17(9): 2762-71. Erratum In: J Clin Oncol 1999 November; 17(11): 3693. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10561351&dopt=Abstract
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Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse. Author(s): Brada M, Hoang-Xuan K, Rampling R, Dietrich PY, Dirix LY, Macdonald D, Heimans JJ, Zonnenberg BA, Bravo-Marques JM, Henriksson R, Stupp R, Yue N, Bruner J, Dugan M, Rao S, Zaknoen S. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2001 February; 12(2): 259-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11300335&dopt=Abstract
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Multicentre CRC phase II trial of temozolomide in recurrent or progressive highgrade glioma. Author(s): Bower M, Newlands ES, Bleehen NM, Brada M, Begent RJ, Calvert H, Colquhoun I, Lewis P, Brampton MH. Source: Cancer Chemotherapy and Pharmacology. 1997; 40(6): 484-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9332462&dopt=Abstract
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Multifaceted resistance of gliomas to temozolomide. Author(s): Bocangel DB, Finkelstein S, Schold SC, Bhakat KK, Mitra S, Kokkinakis DM. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 August; 8(8): 2725-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171906&dopt=Abstract
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New approaches for temozolomide therapy: use in newly diagnosed glioma. Author(s): Stupp R, Newlands E. Source: Seminars in Oncology. 2001 August; 28(4 Suppl 13): 19-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550135&dopt=Abstract
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New approaches in the treatment of metastatic melanoma: thalidomide and temozolomide. Author(s): Hwu WJ. Source: Oncology (Huntingt). 2000 December; 14(12 Suppl 13): 25-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11204670&dopt=Abstract
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New cytotoxic agents for the treatment of metastatic malignant melanoma: temozolomide and related alkylating agents in combination with guanine analogues to abrogate drug resistance. Author(s): Spiro T, Liu L, Gerson S. Source: Forum (Genova). 2000 July-September; 10(3): 274-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11007934&dopt=Abstract
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NICE verdict on Temozolomide: where next? Author(s): Brada M. Source: British Journal of Cancer. 2002 February 12; 86(4): 499-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870526&dopt=Abstract
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O(6)-benzylguanine enhances the in vitro immunotoxic activity of temozolomide on natural or antigen-dependent immunity. Author(s): Alvino E, Pepponi R, Pagani E, Lacal PM, Nunziata C, Bonmassar E, D'Atri S. Source: The Journal of Pharmacology and Experimental Therapeutics. 1999 December; 291(3): 1292-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10565854&dopt=Abstract
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O6-benzylguanine enhances the sensitivity of a glioma xenograft with low O6alkylguanine-DNA alkyltransferase activity to temozolomide and BCNU. Author(s): Wedge SR, Newlands ES. Source: British Journal of Cancer. 1996 May; 73(9): 1049-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8624262&dopt=Abstract
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O6-benzylguanine increases the sensitivity of human primary bone marrow cells to the cytotoxic effects of temozolomide. Author(s): Fairbairn LJ, Watson AJ, Rafferty JA, Elder RH, Margison GP. Source: Experimental Hematology. 1995 February; 23(2): 112-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7828668&dopt=Abstract
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O6-methylguanine formation, repair protein depletion and clinical outcome with a 4 hr schedule of temozolomide in the treatment of advanced melanoma: results of a phase II study. Author(s): Middleton MR, Lee SM, Arance A, Wood M, Thatcher N, Margison GP. Source: International Journal of Cancer. Journal International Du Cancer. 2000 November 1; 88(3): 469-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11054678&dopt=Abstract
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O6-methylguanine-DNA methyltransferase in pretreatment tumour biopsies as a predictor of response to temozolomide in melanoma. Author(s): Middleton MR, Lunn JM, Morris C, Rustin G, Wedge SR, Brampton MH, Lind MJ, Lee SM, Newell DR, Bleehen NM, Newlands ES, Calvert AH, Margison GP, Thatcher N. Source: British Journal of Cancer. 1998 November; 78(9): 1199-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9820180&dopt=Abstract
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Oral temozolomide approved for refractory brain tumor. Author(s): Miller JL. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1999 October 1; 56(19): 1910. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10554903&dopt=Abstract
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p53 effects both the duration of G2/M arrest and the fate of temozolomide-treated human glioblastoma cells. Author(s): Hirose Y, Berger MS, Pieper RO. Source: Cancer Research. 2001 March 1; 61(5): 1957-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11280752&dopt=Abstract
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Pharmacodynamic-mediated reduction of temozolomide tumor concentrations by the angiogenesis inhibitor TNP-470. Author(s): Ma J, Pulfer S, Li S, Chu J, Reed K, Gallo JM. Source: Cancer Research. 2001 July 15; 61(14): 5491-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454697&dopt=Abstract
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Pharmacokinetics of 3-methyl-(triazen-1-yl)imidazole-4-carboximide following administration of temozolomide to patients with advanced cancer. Author(s): Reid JM, Stevens DC, Rubin J, Ames MM. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1997 December; 3(12 Pt 1): 2393-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9815639&dopt=Abstract
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Pharmacokinetics of temozolomide in association with fotemustine in malignant melanoma and malignant glioma patients: comparison of oral, intravenous, and hepatic intra-arterial administration. Author(s): Marzolini C, Decosterd LA, Shen F, Gander M, Leyvraz S, Bauer J, Buclin T, Biollaz J, Lejeune F. Source: Cancer Chemotherapy and Pharmacology. 1998; 42(6): 433-40. Erratum In: Cancer Chemother Pharmacol 1999; 43(5): 439-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9788568&dopt=Abstract
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Phase I and pharmacokinetic study of temozolomide on a daily-for-5-days schedule in patients with advanced solid malignancies. Author(s): Hammond LA, Eckardt JR, Baker SD, Eckhardt SG, Dugan M, Forral K, Reidenberg P, Statkevich P, Weiss GR, Rinaldi DA, Von Hoff DD, Rowinsky EK. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1999 August; 17(8): 2604-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10561328&dopt=Abstract
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Phase I dose-escalation and pharmacokinetic study of temozolomide (SCH 52365) for refractory or relapsing malignancies. Author(s): Brada M, Judson I, Beale P, Moore S, Reidenberg P, Statkevich P, Dugan M, Batra V, Cutler D. Source: British Journal of Cancer. 1999 November; 81(6): 1022-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10576660&dopt=Abstract
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Phase I study of Gliadel wafers plus temozolomide in adults with recurrent supratentorial high-grade gliomas. Author(s): Gururangan S, Cokgor L, Rich JN, Edwards S, Affronti ML, Quinn JA, Herndon JE 2nd, Provenzale JM, McLendon RE, Tourt-Uhlig S, Sampson JH, StaffordFox V, Zaknoen S, Early M, Friedman AH, Friedman HS. Source: Neuro-Oncology. 2001 October; 3(4): 246-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11584894&dopt=Abstract
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Phase I study of temozolomide and escalating doses of oral etoposide for adults with recurrent malignant glioma. Author(s): Korones DN, Benita-Weiss M, Coyle TE, Mechtler L, Bushunow P, Evans B, Reardon DA, Quinn JA, Friedman H. Source: Cancer. 2003 April 15; 97(8): 1963-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673724&dopt=Abstract
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Phase I study of temozolomide in children and adolescents with recurrent solid tumors: a report from the Children's Cancer Group. Author(s): Nicholson HS, Krailo M, Ames MM, Seibel NL, Reid JM, Liu-Mares W, Vezina LG, Ettinger AG, Reaman GH. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1998 September; 16(9): 3037-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9738573&dopt=Abstract
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Phase I study of temozolomide in paediatric patients with advanced cancer. United Kingdom Children's Cancer Study Group. Author(s): Estlin EJ, Lashford L, Ablett S, Price L, Gowing R, Gholkar A, Kohler J, Lewis IJ, Morland B, Pinkerton CR, Stevens MC, Mott M, Stevens R, Newell DR, Walker D, Dicks-Mireaux C, McDowell H, Reidenberg P, Statkevich P, Marco A, Batra V, Dugan M, Pearson AD. Source: British Journal of Cancer. 1998 September; 78(5): 652-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9744506&dopt=Abstract
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Phase I study of temozolomide in relapsed/refractory acute leukemia. Author(s): Seiter K, Liu D, Loughran T, Siddiqui A, Baskind P, Ahmed T. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 August 1; 20(15): 3249-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149298&dopt=Abstract
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Phase I trial of temozolomide (CCRG 81045: M&B 39831: NSC 362856). Author(s): Newlands ES, Blackledge GR, Slack JA, Rustin GJ, Smith DB, Stuart NS, Quarterman CP, Hoffman R, Stevens MF, Brampton MH, et al. Source: British Journal of Cancer. 1992 February; 65(2): 287-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1739631&dopt=Abstract
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Phase I trial of temozolomide (NSC 362856) in patients with advanced cancer. Author(s): Dhodapkar M, Rubin J, Reid JM, Burch PA, Pitot HC, Buckner JC, Ames MM, Suman VJ. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1997 July; 3(7): 1093-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9815788&dopt=Abstract
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Phase I trial of temozolomide using an extended continuous oral schedule. Author(s): Brock CS, Newlands ES, Wedge SR, Bower M, Evans H, Colquhoun I, Roddie M, Glaser M, Brampton MH, Rustin GJ. Source: Cancer Research. 1998 October 1; 58(19): 4363-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9766665&dopt=Abstract
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Phase I. Trial of irinotecan and temozolomide in patients with solid tumors. Author(s): Jones SF, Gian VG, Greco FA, Miranda FT, Shipley DL, Thompson DS, Hainsworth JD, Toomey MA, Willcutt NT, Burris HA 3rd. Source: Oncology (Huntingt). 2003 May; 17(5 Suppl 5): 41-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800606&dopt=Abstract
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Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma: a North American Brain Tumor Consortium study. Author(s): Jaeckle KA, Hess KR, Yung WK, Greenberg H, Fine H, Schiff D, Pollack IF, Kuhn J, Fink K, Mehta M, Cloughesy T, Nicholas MK, Chang S, Prados M; North American Brain Tumor Consortium. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 June 15; 21(12): 2305-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12805331&dopt=Abstract
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Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases. Author(s): Antonadou D, Paraskevaidis M, Sarris G, Coliarakis N, Economou I, Karageorgis P, Throuvalas N. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 September 1; 20(17): 3644-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202665&dopt=Abstract
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Phase II study of first-line chemotherapy with temozolomide in recurrent oligodendroglial tumors: the European Organization for Research and Treatment of Cancer Brain Tumor Group Study 26971. Author(s): van den Bent MJ, Taphoorn MJ, Brandes AA, Menten J, Stupp R, Frenay M, Chinot O, Kros JM, van der Rijt CC, Vecht ChJ, Allgeier A, Gorlia T; European Organization for Research and Treatment of Cancer Brain Tumor Group. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 July 1; 21(13): 2525-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829671&dopt=Abstract
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Phase II study of temozolomide in heavily pretreated cancer patients with brain metastases. Author(s): Christodoulou C, Bafaloukos D, Kosmidis P, Samantas E, Bamias A, Papakostas P, Karabelis A, Bacoyiannis C, Skarlos DV; Hellenic Cooperative Oncology Group. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2001 February; 12(2): 249-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11300333&dopt=Abstract
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Phase II study of temozolomide in patients with relapsing high grade glioma and poor performance status. Author(s): Janinis J, Efstathiou E, Panopoulos C, Samantas E, Aravantinos G, Christodoulou C, Skarlos D. Source: Medical Oncology (Northwood, London, England). 2000 May; 17(2): 106-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10871815&dopt=Abstract
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Phase II study of temozolomide plus thalidomide for the treatment of metastatic melanoma. Author(s): Hwu WJ, Krown SE, Menell JH, Panageas KS, Merrell J, Lamb LA, Williams LJ, Quinn CJ, Foster T, Chapman PB, Livingston PO, Wolchok JD, Houghton AN. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 September 1; 21(17): 3351-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947072&dopt=Abstract
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Phase II trial of temozolomide in low-grade non-Hodgkin's lymphoma. Author(s): Woll PJ, Crowther D, Johnson PW, Soukop M, Harper PG, Harris M, Brampton MH, Newlands ES. Source: British Journal of Cancer. 1995 July; 72(1): 183-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7599050&dopt=Abstract
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Phase II trial of temozolomide in patients with progressive low-grade glioma. Author(s): Quinn JA, Reardon DA, Friedman AH, Rich JN, Sampson JH, Provenzale JM, McLendon RE, Gururangan S, Bigner DD, Herndon JE 2nd, Avgeropoulos N, Finlay J, Tourt-Uhlig S, Affronti ML, Evans B, Stafford-Fox V, Zaknoen S, Friedman HS. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 February 15; 21(4): 646-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586801&dopt=Abstract
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Phase II trial of temozolomide plus the matrix metalloproteinase inhibitor, marimastat, in recurrent and progressive glioblastoma multiforme. Author(s): Groves MD, Puduvalli VK, Hess KR, Jaeckle KA, Peterson P, Yung WK, Levin VA. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 March 1; 20(5): 1383-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870183&dopt=Abstract
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Poly(ADP-ribose) polymerase inhibitor increases growth inhibition and reduces G(2)/M cell accumulation induced by temozolomide in malignant glioma cells. Author(s): Tentori L, Portarena I, Torino F, Scerrati M, Navarra P, Graziani G. Source: Glia. 2002 October; 40(1): 44-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12237842&dopt=Abstract
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Population pharmacokinetics of temozolomide in cancer patients. Author(s): Jen JF, Cutler DL, Pai SM, Batra VK, Affrime MB, Zambas DN, Heft S, Hajian G. Source: Pharmaceutical Research. 2000 October; 17(10): 1284-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11145236&dopt=Abstract
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Possible efficacy of temozolomide in a patient with gliomatosis cerebri. Author(s): Benjelloun A, Delavelle J, Lazeyras F, Dietrich PY. Source: Neurology. 2001 November 27; 57(10): 1932-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11723300&dopt=Abstract
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Post hoc economic analysis of temozolomide versus dacarbazine in the treatment of advanced metastatic melanoma. Author(s): Hillner BE, Agarwala S, Middleton MR. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2000 April; 18(7): 1474-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10735895&dopt=Abstract
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Potentiation of temozolomide and BCNU cytotoxicity by O(6)-benzylguanine: a comparative study in vitro. Author(s): Wedge SR, Porteus JK, May BL, Newlands ES. Source: British Journal of Cancer. 1996 February; 73(4): 482-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8595163&dopt=Abstract
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Potentiation of temozolomide and topotecan growth inhibition and cytotoxicity by novel poly(adenosine diphosphoribose) polymerase inhibitors in a panel of human tumor cell lines. Author(s): Delaney CA, Wang LZ, Kyle S, White AW, Calvert AH, Curtin NJ, Durkacz BW, Hostomsky Z, Newell DR. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 July; 6(7): 2860-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10914735&dopt=Abstract
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Preclinical antitumor activity of temozolomide in mice: efficacy against human brain tumor xenografts and synergism with 1,3-bis(2-chloroethyl)-1-nitrosourea. Author(s): Plowman J, Waud WR, Koutsoukos AD, Rubinstein LV, Moore TD, Grever MR. Source: Cancer Research. 1994 July 15; 54(14): 3793-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8033099&dopt=Abstract
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Prevention of irradiation-induced glioma cell invasion by temozolomide involves caspase 3 activity and cleavage of focal adhesion kinase. Author(s): Wick W, Wick A, Schulz JB, Dichgans J, Rodemann HP, Weller M. Source: Cancer Research. 2002 March 15; 62(6): 1915-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11912174&dopt=Abstract
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Promising survival and concomitant radiation plus temozolomide followed by adjuvant temozolomide. Author(s): Beauchesne P. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 July 15; 20(14): 3180-1; Author Reply 3181. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12118035&dopt=Abstract
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Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. Author(s): Stupp R, Dietrich PY, Ostermann Kraljevic S, Pica A, Maillard I, Maeder P, Meuli R, Janzer R, Pizzolato G, Miralbell R, Porchet F, Regli L, de Tribolet N, Mirimanoff RO, Leyvraz S. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 March 1; 20(5): 1375-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870182&dopt=Abstract
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Randomized phase II study of temozolomide given every 8 hours or daily with either interferon alfa-2b or thalidomide in metastatic malignant melanoma. Author(s): Danson S, Lorigan P, Arance A, Clamp A, Ranson M, Hodgetts J, Lomax L, Ashcroft L, Thatcher N, Middleton MR. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 July 1; 21(13): 2551-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829675&dopt=Abstract
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Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. Author(s): Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, Gore M, Aamdal S, Cebon J, Coates A, Dreno B, Henz M, Schadendorf D, Kapp A, Weiss J, Fraass U, Statkevich P, Muller M, Thatcher N. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2000 January; 18(1): 158-66. Erratum In: J Clin Oncol 2000 June; 18(11): 2351. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10623706&dopt=Abstract
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Resistance-modifying agents. 8. Inhibition of O(6)-alkylguanine-DNA alkyltransferase by O(6)-alkenyl-, O(6)-cycloalkenyl-, and O(6)-(2-oxoalkyl)guanines and potentiation of temozolomide cytotoxicity in vitro by O(6)-(1cyclopentenylmethyl)guanine. Author(s): Griffin RJ, Arris CE, Bleasdale C, Boyle FT, Calvert AH, Curtin NJ, Dalby C, Kanugula S, Lembicz NK, Newell DR, Pegg AE, Golding BT. Source: Journal of Medicinal Chemistry. 2000 November 2; 43(22): 4071-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11063604&dopt=Abstract
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Response to low dose temozolomide in radiation induced gliomatosis cerebri. Author(s): Hargrave D, Bouffet E, Gammon J, Becker L, Rutka J, Baruchel S. Source: Medical and Pediatric Oncology. 2003 December; 41(6): 562-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14595716&dopt=Abstract
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Role of O6-methylguanine-DNA methyltransferase in resistance of human brain tumor cell lines to the clinically relevant methylating agents temozolomide and streptozotocin. Author(s): Bobola MS, Tseng SH, Blank A, Berger MS, Silber JR. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1996 April; 2(4): 735-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9816224&dopt=Abstract
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Role of wild-type p53 on the antineoplastic activity of temozolomide alone or combined with inhibitors of poly(ADP-ribose) polymerase. Author(s): Tentori L, Lacal PM, Benincasa E, Franco D, Faraoni I, Bonmassar E, Graziani G. Source: The Journal of Pharmacology and Experimental Therapeutics. 1998 May; 285(2): 884-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9580640&dopt=Abstract
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Safety and efficacy of temozolomide in patients with recurrent anaplastic oligodendrogliomas after standard radiotherapy and chemotherapy. Author(s): Chinot OL, Honore S, Dufour H, Barrie M, Figarella-Branger D, Muracciole X, Braguer D, Martin PM, Grisoli F. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 May 1; 19(9): 2449-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11331324&dopt=Abstract
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Salvage therapy with temozolomide in an immunocompetent patient with primary brain lymphoma. Author(s): Reni M, Ferreri AJ, Landoni C, Villa E. Source: Journal of the National Cancer Institute. 2000 April 5; 92(7): 575-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10749917&dopt=Abstract
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Schedule-dependent activity of temozolomide plus CPT-11 against a human central nervous system tumor-derived xenograft. Author(s): Patel VJ, Elion GB, Houghton PJ, Keir S, Pegg AE, Johnson SP, Dolan ME, Bigner DD, Friedman HS. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 October; 6(10): 4154-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11051270&dopt=Abstract
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Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972. Author(s): van den Bent MJ, Chinot O, Boogerd W, Bravo Marques J, Taphoorn MJ, Kros JM, van der Rijt CC, Vecht CJ, De Beule N, Baron B. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 April; 14(4): 599-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649108&dopt=Abstract
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Sensitivity of short-term cultures derived from human malignant glioma to the anticancer drug temozolomide. Author(s): Sankar A, Thomas DG, Darling JL. Source: Anti-Cancer Drugs. 1999 February; 10(2): 179-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10211548&dopt=Abstract
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Sequential administration of temozolomide and fotemustine: depletion of O6-alkyl guanine-DNA transferase in blood lymphocytes and in tumours. Author(s): Gander M, Leyvraz S, Decosterd L, Bonfanti M, Marzolini C, Shen F, Lienard D, Perey L, Colella G, Biollaz J, Lejeune F, Yarosh D, Belanich M, D'Incalci M. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 1999 July; 10(7): 831-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10470431&dopt=Abstract
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Simultaneous protection of G156A methylguanine DNA methyltransferase genetransduced hematopoietic progenitors and sensitization of tumor cells using O6benzylguanine and temozolomide. Author(s): Reese JS, Davis BM, Liu L, Gerson SL. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1999 January; 5(1): 163-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9918215&dopt=Abstract
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Survival of human glioma cells treated with various combination of temozolomide and X-rays. Author(s): van Rijn J, Heimans JJ, van den Berg J, van der Valk P, Slotman BJ. Source: International Journal of Radiation Oncology, Biology, Physics. 2000 June 1; 47(3): 779-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10837964&dopt=Abstract
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Temozolomide (Temodal) for treatment of primary brain tumours. Author(s): MacConnachie AM. Source: Intensive & Critical Care Nursing : the Official Journal of the British Association of Critical Care Nurses. 2000 February; 16(1): 59-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10790718&dopt=Abstract
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Temozolomide (Temodar). Author(s): Bruce S. Source: Clinical Journal of Oncology Nursing. 2001 January-February; 5(1): 37-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11899402&dopt=Abstract
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Temozolomide and cisplatin in the treatment of leptomeningeal metastatic involvement from melanoma: a case report. Author(s): Salmaggi A, Silvani A, Eoli M, Lamperti E, Boiardi A. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2002 December; 23(5): 257-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528690&dopt=Abstract
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Temozolomide and treatment of malignant glioma. Author(s): Friedman HS, Kerby T, Calvert H. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 July; 6(7): 2585-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10914698&dopt=Abstract
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Temozolomide and whole brain irradiation in melanoma metastatic to the brain: a phase II trial of the Cytokine Working Group. Author(s): Margolin K, Atkins B, Thompson A, Ernstoff S, Weber J, Flaherty L, Clark I, Weiss G, Sosman J, II Smith W, Dutcher P, Gollob J, Longmate J, Johnson D. Source: Journal of Cancer Research and Clinical Oncology. 2002 April; 128(4): 214-8. Epub 2002 March 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11935312&dopt=Abstract
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Temozolomide as a second-line systemic regimen in recurrent high-grade glioma: a phase II study. Author(s): Brandes AA, Ermani M, Basso U, Amista P, Berti F, Scienza R, Rotilio A, Pinna G, Gardiman M, Monfardini S. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2001 February; 12(2): 255-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11300334&dopt=Abstract
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Temozolomide as an alternative to irradiation for elderly patients with newly diagnosed malignant gliomas. Author(s): Glantz M, Chamberlain M, Liu Q, Litofsky NS, Recht LD. Source: Cancer. 2003 May 1; 97(9): 2262-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712481&dopt=Abstract
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Temozolomide as second-line chemotherapy for relapsed gliomas. Author(s): Trent S, Kong A, Short SC, Traish D, Ashley S, Dowe A, Hines F, Brada M. Source: Journal of Neuro-Oncology. 2002 May; 57(3): 247-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12125988&dopt=Abstract
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Temozolomide chemotherapy in recurrent oligodendroglioma. Author(s): van den Bent MJ, Keime-Guibert F, Brandes AA, Taphoorn MJ, Kros JM, Eskens FA, Carpentier AF. Source: Neurology. 2001 July 24; 57(2): 340-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11468326&dopt=Abstract
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Temozolomide delivered by intracerebral microinfusion is safe and efficacious against malignant gliomas in rats. Author(s): Heimberger AB, Archer GE, McLendon RE, Hulette C, Friedman AH, Friedman HS, Bigner DD, Sampson JH. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 October; 6(10): 4148-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11051269&dopt=Abstract
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Temozolomide enhances herpes simplex virus thymidine kinase/ganciclovir therapy of malignant glioma. Author(s): Rainov NG, Fels C, Droege JW, Schafer C, Kramm CM, Chou TC. Source: Cancer Gene Therapy. 2001 September; 8(9): 662-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11593335&dopt=Abstract
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Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFN alpha in patients with metastatic melanoma. Author(s): de Gast GC, Batchelor D, Kersten MJ, Vyth-Dreese FA, Sein J, van de Kasteele WF, Nooijen WJ, Nieweg OE, de Waal MA, Boogerd W. Source: British Journal of Cancer. 2003 January 27; 88(2): 175-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610499&dopt=Abstract
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Temozolomide for advanced, metastatic melanoma. Author(s): Cohen MH, Johnson JR, Middleton MR. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2000 May; 18(10): 2185. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10811684&dopt=Abstract
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Temozolomide for malignant brain tumours. Author(s): Batchelor T. Source: Lancet. 2000 April 1; 355(9210): 1115-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10791369&dopt=Abstract
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Temozolomide for recurrent high-grade glioma. Author(s): Macdonald DR. Source: Seminars in Oncology. 2001 August; 28(4 Suppl 13): 3-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550133&dopt=Abstract
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Temozolomide for treating brain metastases. Author(s): Abrey LE, Christodoulou C. Source: Seminars in Oncology. 2001 August; 28(4 Suppl 13): 34-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550137&dopt=Abstract
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Temozolomide in adult patients with advanced soft tissue sarcoma: a phase II study of the EORTC Soft Tissue and Bone Sarcoma Group. Author(s): Woll PJ, Judson I, Lee SM, Rodenhuis S, Nielsen OS, Buesa JM, Lorigan PC, Leyvraz S, Hermans C, van Glabbeke M, Verweij J. Source: European Journal of Cancer (Oxford, England : 1990). 1999 March; 35(3): 410-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10448291&dopt=Abstract
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Temozolomide in combination with docetaxel in patients with advanced melanoma: a phase II study of the Hellenic Cooperative Oncology Group. Author(s): Bafaloukos D, Gogas H, Georgoulias V, Briassoulis E, Fountzilas G, Samantas E, Kalofonos Ch, Skarlos D, Karabelis A, Kosmidis P. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 January 15; 20(2): 420-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11786569&dopt=Abstract
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Temozolomide in combination with interferon alpha-2b in patients with metastatic melanoma: a phase I dose-escalation study. Author(s): Agarwala SS, Kirkwood JM. Source: Cancer. 2003 January 1; 97(1): 121-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12491513&dopt=Abstract
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Temozolomide in combination with other cytotoxic agents. Author(s): Prados M. Source: Seminars in Oncology. 2001 August; 28(4 Suppl 13): 24-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550136&dopt=Abstract
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Temozolomide in early stages of newly diagnosed malignant glioma and neoplastic meningitis. Author(s): Friedman HS. Source: Seminars in Oncology. 2000 June; 27(3 Suppl 6): 35-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10866348&dopt=Abstract
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Temozolomide in glioblastoma multiforme of the elderly. Author(s): Brandes AA, Vastola F, Basso U, Pasetto LM, Ermani M, Berti F, Rotilio A, Amista P, Scienza R, Monfardini S. Source: Tumori. 2002 January-February; 88(1 Suppl 1): S69-70. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11989929&dopt=Abstract
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Temozolomide in malignant gliomas of childhood: a United Kingdom Children's Cancer Study Group and French Society for Pediatric Oncology Intergroup Study. Author(s): Lashford LS, Thiesse P, Jouvet A, Jaspan T, Couanet D, Griffiths PD, Doz F, Ironside J, Robson K, Hobson R, Dugan M, Pearson AD, Vassal G, Frappaz D; a United Kingdom Children's Cancer Study Group and French Society for Pediatric Oncology Intergroup Study. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 December 15; 20(24): 4684-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488414&dopt=Abstract
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Temozolomide in malignant gliomas. Author(s): Yung WK. Source: Seminars in Oncology. 2000 June; 27(3 Suppl 6): 27-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10866347&dopt=Abstract
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Temozolomide in patients with advanced non-small cell lung cancer with and without brain metastases. a phase II study of the EORTC Lung Cancer Group (08965). Author(s): Dziadziuszko R, Ardizzoni A, Postmus PE, Smit EF, Price A, Debruyne C, Legrand C, Giaccone G; EORTC Lung Cancer Group. Source: European Journal of Cancer (Oxford, England : 1990). 2003 June; 39(9): 1271-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763216&dopt=Abstract
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Temozolomide in patients with glioblastoma at second relapse after first line nitrosourea-procarbazine failure: a phase II study. Author(s): Brandes AA, Ermani M, Basso U, Paris MK, Lumachi F, Berti F, Amista P, Gardiman M, Iuzzolino P, Turazzi S, Monfardini S. Source: Oncology. 2002; 63(1): 38-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12187069&dopt=Abstract
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Temozolomide in patients with high grade gliomas. Author(s): Brandes AA, Pasetto LM, Vastola F, Monfardini S. Source: Oncology. 2000 September; 59(3): 181-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11053983&dopt=Abstract
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Temozolomide in second-line treatment after prior nitrosurea-based chemotherapy in glioblastoma multiforme: experience from a Portuguese institution. Author(s): Teixeira MM, Garcia I, Portela I, Cernuda M, Oliveira C, Albano J, Lima L. Source: Int J Clin Pharmacol Res. 2002; 22(1): 19-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12395915&dopt=Abstract
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Temozolomide induced differentiation of K562 leukemia cells is not mediated by gene hypomethylation. Author(s): Zucchetti M, Catapano CV, Filippeschi S, Erba E, D'Incalci M. Source: Biochemical Pharmacology. 1989 July 1; 38(13): 2069-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2660797&dopt=Abstract
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Temozolomide induces apoptosis and senescence in glioma cells cultured as multicellular spheroids. Author(s): Gunther W, Pawlak E, Damasceno R, Arnold H, Terzis AJ. Source: British Journal of Cancer. 2003 February 10; 88(3): 463-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569392&dopt=Abstract
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Temozolomide is active in childhood, progressive, unresectable, low-grade gliomas. Author(s): Kuo DJ, Weiner HL, Wisoff J, Miller DC, Knopp EA, Finlay JL. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2003 May; 25(5): 372-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759623&dopt=Abstract
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Temozolomide plus thalidomide in patients with advanced melanoma: results of a dose-finding trial. Author(s): Hwu WJ, Krown SE, Panageas KS, Menell JH, Chapman PB, Livingston PO, Williams LJ, Quinn CJ, Houghton AN. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 June 1; 20(11): 2610-5. Erratum In: J Clin Oncol 2002 August 1; 20(15): 3361. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12039921&dopt=Abstract
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Temozolomide, a novel alkylating agent with activity in the central nervous system, may improve the treatment of advanced metastatic melanoma. Author(s): Agarwala SS, Kirkwood JM. Source: The Oncologist. 2000; 5(2): 144-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10794805&dopt=Abstract
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Temozolomide. A new option for high-grade astrocytomas. Author(s): Schwenka J, Ignoffo RJ. Source: Cancer Practice. 2000 November-December; 8(6): 311-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898150&dopt=Abstract
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Temozolomide: a new oral cytotoxic chemotherapeutic agent with promising activity against primary brain tumours. Author(s): O'Reilly SM, Newlands ES, Glaser MG, Brampton M, Rice-Edwards JM, Illingworth RD, Richards PG, Kennard C, Colquhoun IR, Lewis P, et al. Source: European Journal of Cancer (Oxford, England : 1990). 1993; 29A(7): 940-2. Erratum In: Eur J Cancer 1993; 29A(10): 1500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8499146&dopt=Abstract
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Temozolomide: a review of its discovery, chemical properties, pre-clinical development and clinical trials. Author(s): Newlands ES, Stevens MF, Wedge SR, Wheelhouse RT, Brock C. Source: Cancer Treatment Reviews. 1997 January; 23(1): 35-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9189180&dopt=Abstract
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Temozolomide: the effect of once- and twice-a-day dosing on tumor tissue levels of the DNA repair protein O(6)-alkylguanine-DNA-alkyltransferase. Author(s): Spiro TP, Liu L, Majka S, Haaga J, Willson JK, Gerson SL. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2001 August; 7(8): 2309-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11489806&dopt=Abstract
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Temozolomide: too early for definitive conclusions. Author(s): Brown P, Buckner J. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 October 1; 21(19): 3710. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512412&dopt=Abstract
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Temozolomide-induced flare in high-grade gliomas: a new clinical entity. Author(s): Rosenthal MA, Ashley DL, Cher L. Source: Internal Medicine Journal. 2002 July; 32(7): 346-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088355&dopt=Abstract
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The Charing Cross Hospital experience with temozolomide in patients with gliomas. Author(s): Newlands ES, O'Reilly SM, Glaser MG, Bower M, Evans H, Brock C, Brampton MH, Colquhoun I, Lewis P, Rice-Edwards JM, Illingworth RD, Richards PG. Source: European Journal of Cancer (Oxford, England : 1990). 1996 December; 32A(13): 2236-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9038604&dopt=Abstract
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The effect of O6-alkylguanine-DNA alkyltransferase and mismatch repair activities on the sensitivity of human melanoma cells to temozolomide, 1,3-bis(2-chloroethyl)1nitrosourea, and cisplatin. Author(s): Pepponi R, Marra G, Fuggetta MP, Falcinelli S, Pagani E, Bonmassar E, Jiricny J, D'Atri S. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 February; 304(2): 661-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538819&dopt=Abstract
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The effectiveness and cost-effectiveness of temozolomide for the treatment of recurrent malignant glioma: a rapid and systematic review. Author(s): Dinnes J, Cave C, Huang S, Major K, Milne R. Source: Health Technology Assessment (Winchester, England). 2001; 5(13): 1-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11359682&dopt=Abstract
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The use of temozolomide in recurrent malignant gliomas. Author(s): Gaya A, Rees J, Greenstein A, Stebbing J. Source: Cancer Treatment Reviews. 2002 April; 28(2): 115-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297119&dopt=Abstract
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Thresholds of O6-alkylguanine-DNA alkyltransferase which confer significant resistance of human glial tumor xenografts to treatment with 1,3-bis(2-chloroethyl)-1nitrosourea or temozolomide. Author(s): Kokkinakis DM, Bocangel DB, Schold SC, Moschel RC, Pegg AE. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2001 February; 7(2): 421-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11234899&dopt=Abstract
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Tolerance of human MSH2+/- lymphoblastoid cells to the methylating agent temozolomide. Author(s): Marra G, D'Atri S, Corti C, Bonmassar L, Cattaruzza MS, Schweizer P, Heinimann K, Bartosova Z, Nystrom-Lahti M, Jiricny J. Source: Proceedings of the National Academy of Sciences of the United States of America. 2001 June 19; 98(13): 7164-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11416201&dopt=Abstract
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Treatment of brain metastases of malignant melanoma with temozolomide. Author(s): Biasco G, Pantaleo MA, Casadei S. Source: The New England Journal of Medicine. 2001 August 23; 345(8): 621-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11529230&dopt=Abstract
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Treatment of leptomeningeal relapse of medulloblastoma with temozolomide. Author(s): Hongeng S, Visudtibhan A, Dhanachai M, Laothamatus J, Chiamchanya S. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2002 October; 24(7): 591-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368706&dopt=Abstract
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Treatment of metastatic melanoma in the brain with temozolomide and thalidomide. Author(s): Hwu WJ, Raizer J, Panageas KS, Lis E. Source: The Lancet Oncology. 2001 October; 2(10): 634-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11902555&dopt=Abstract
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Treatment of neoplastic meningitis with intrathecal temozolomide. Author(s): Sampson JH, Archer GE, Villavicencio AT, McLendon RE, Friedman AH, Bishop WR, Bigner DD, Friedman HS. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1999 May; 5(5): 1183-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10353755&dopt=Abstract
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Treatment with temozolomide and poly(ADP-ribose) polymerase inhibitors induces early apoptosis and increases base excision repair gene transcripts in leukemic cells resistant to triazene compounds. Author(s): Tentori L, Turriziani M, Franco D, Serafino A, Levati L, Roy R, Bonmassar E, Graziani G. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1999 June; 13(6): 901-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10360379&dopt=Abstract
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Use of temozolomide with other cytotoxic chemotherapy in the treatment of patients with recurrent brain metastases from lung cancer. Author(s): Ebert BL, Niemierko E, Shaffer K, Salgia R. Source: The Oncologist. 2003; 8(1): 69-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604733&dopt=Abstract
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CHAPTER 2. NUTRITION AND TEMOZOLOMIDE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and temozolomide.
Finding Nutrition Studies on Temozolomide 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 “temozolomide” (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 “temozolomide” (or a synonym): •
A phase II pilot trial of concurrent biochemotherapy with cisplatin, vinblastine, temozolomide, interleukin 2, and IFN-alpha 2B in patients with metastatic melanoma. Author(s): Department of Medicine, Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
[email protected] Source: Atkins, M B Gollob, J A Sosman, J A McDermott, D F Tutin, L Sorokin, P Parker, R A Mier, J W Clin-Cancer-Res. 2002 October; 8(10): 3075-81 1078-0432
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Abrogation of the Chk1-mediated G(2) checkpoint pathway potentiates temozolomide-induced toxicity in a p53-independent manner in human glioblastoma cells. Author(s): Brain Tumor Research Center, Department of Neurological Surgery, University of California-San Francisco, 2340 Sutter Street, San Francisco, CA 94143-0875, USA. Source: Hirose, Y Berger, M S Pieper, R O Cancer-Res. 2001 August 1; 61(15): 5843-9 0008-5472
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Antitumor activity of temozolomide combined with irinotecan is partly independent of O6-methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models. Author(s): Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA.
[email protected] Source: Houghton, P J Stewart, C F Cheshire, P J Richmond, L B Kirstein, M N Poquette, C A Tan, M Friedman, H S Brent, T P Clin-Cancer-Res. 2000 October; 6(10): 4110-8 10780432
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Biochemical changes associated with a multidrug-resistant phenotype of a human glioma cell line with temozolomide-acquired resistance. Author(s): Department of Pharmacology, Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA 19111, USA. Source: Ma, Jianguo Murphy, Maureen O'Dwyer, Peter J Berman, Eric Reed, Karin Gallo, James M Biochem-Pharmacol. 2002 April 1; 63(7): 1219-28 0006-2952
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Evaluation of temozolomide in a SCID mouse model of human B-cell precursor leukemia. Author(s): Parker Hughes Cancer Center, Department of Experimental Oncology, Hughes Institute, St. Paul, MN 55113, USA. Source: Messinger, Y Reaman, G H Ek, O Uckun, F M Leuk-Lymphoma. 1999 April; 33(3-4): 289-93 1042-8194
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Future directions in the treatment of malignant gliomas with temozolomide. Author(s): Department of Neurosurgery, University of California, San Francisco 94143, USA. Source: Prados, M D Semin-Oncol. 2000 June; 27(3 Suppl 6): 41-6 0093-7754
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Involvement of the mismatch repair system in temozolomide-induced apoptosis. Author(s): Istituto Dermopatico Dell'Immacolata, Rome, Italy.
[email protected] Source: D'Atri, S Tentori, L Lacal, P M Graziani, G Pagani, E Benincasa, E Zambruno, G Bonmassar, E Jiricny, J Mol-Pharmacol. 1998 August; 54(2): 334-41 0026-895X
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Pharmacodynamic-mediated reduction of temozolomide tumor concentrations by the angiogenesis inhibitor TNP-470. Author(s): Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. Source: Ma, J Pulfer, S Li, S Chu, J Reed, K Gallo, J M Cancer-Res. 2001 July 15; 61(14): 5491-8 0008-5472
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Schedule-dependent activity of temozolomide plus CPT-11 against a human central nervous system tumor-derived xenograft. Author(s): Department of Surgery, Pathology [Duke University Medical Center, Durham, North Carolina 27710, USA. Source: Patel, V J Elion, G B Houghton, P J Keir, S Pegg, A E Johnson, S P Dolan, M E Bigner, D D Friedman, H S Clin-Cancer-Res. 2000 October; 6(10): 4154-7 1078-0432
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Temozolomide in combination with docetaxel in patients with advanced melanoma: a phase II study of the Hellenic Cooperative Oncology Group. Author(s): Metaxa's Cancer Hospital, Piraeus, Greece.
[email protected] Source: Bafaloukos, D Gogas, H Georgoulias, V Briassoulis, E Fountzilas, G Samantas, E Kalofonos, Ch Skarlos, D Karabelis, A Kosmidis, P J-Clin-Oncol. 2002 January 15; 20(2): 420-5 0732-183X
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/
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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. TEMOZOLOMIDE
ALTERNATIVE
MEDICINE
AND
Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to temozolomide. 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 temozolomide 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 “temozolomide” (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 temozolomide: •
A phase II pilot trial of concurrent biochemotherapy with cisplatin, vinblastine, temozolomide, interleukin 2, and IFN-alpha 2B in patients with metastatic melanoma. Author(s): Atkins MB, Gollob JA, Sosman JA, McDermott DF, Tutin L, Sorokin P, Parker RA, Mier JW. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 October; 8(10): 3075-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374674&dopt=Abstract
•
A prospective study on glioblastoma in the elderly. Author(s): Brandes AA, Vastola F, Basso U, Berti F, Pinna G, Rotilio A, Gardiman M, Scienza R, Monfardini S, Ermani M. Source: Cancer. 2003 February 1; 97(3): 657-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548608&dopt=Abstract
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Adults with newly diagnosed high-grade gliomas. Author(s): Croteau D, Mikkelsen T. Source: Curr Treat Options Oncol. 2001 December; 2(6): 507-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12057096&dopt=Abstract
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Advances in diagnosis and management of oligodendroglioma. Author(s): Hussein MR, Baidas S. Source: Expert Rev Anticancer Ther. 2002 October; 2(5): 520-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12382520&dopt=Abstract
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Antitumor activity of temozolomide combined with irinotecan is partly independent of O6-methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models. Author(s): Houghton PJ, Stewart CF, Cheshire PJ, Richmond LB, Kirstein MN, Poquette CA, Tan M, Friedman HS, Brent TP. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 October; 6(10): 4110-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11051264&dopt=Abstract
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Antitumoral action of 2-deoxy-D-glucose tetraacetate in human melanoma cells. Author(s): Reinhold U, Ugurel S, Tilgen W, Kadiata MM, Olivares E, Nadi AB, Malaisse WJ. Source: Oncol Rep. 2000 September-October; 7(5): 1093-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10948345&dopt=Abstract
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Biochemical changes associated with a multidrug-resistant phenotype of a human glioma cell line with temozolomide-acquired resistance. Author(s): Ma J, Murphy M, O'Dwyer PJ, Berman E, Reed K, Gallo JM. Source: Biochemical Pharmacology. 2002 April 1; 63(7): 1219-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11960598&dopt=Abstract
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Brain metastases from fallopian tube carcinoma responsive to intra-arterial carboplatin and intravenous etoposide: a case report. Author(s): Newton HB, Stevens C, Santi M. Source: Journal of Neuro-Oncology. 2001 December; 55(3): 179-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11859973&dopt=Abstract
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Characterization of paclitaxel (Taxol) sensitivity in human glioma- and medulloblastoma-derived cell lines. Author(s): Tseng SH, Bobola MS, Berger MS, Silber JR. Source: Neuro-Oncology. 1999 April; 1(2): 101-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550305&dopt=Abstract
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Chemotherapy for the treatment of oligodendroglial tumors. Author(s): Chinot O. Source: Seminars in Oncology. 2001 August; 28(4 Suppl 13): 13-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550134&dopt=Abstract
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Combined treatment with high-dose methotrexate, vincristine and procarbazine, without intrathecal chemotherapy, followed by consolidation radiotherapy for primary central nervous system lymphoma in immunocompetent patients. Author(s): Ferreri AJ, Reni M, Dell'Oro S, Ciceri F, Bernardi M, Camba L, Ponzoni M, Terreni MR, Tomirotti M, Spina M, Villa E. Source: Oncology. 2001; 60(2): 134-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11244328&dopt=Abstract
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Current chemotherapy for glioblastoma. Author(s): Parney IF, Chang SM. Source: Cancer Journal (Sudbury, Mass.). 2003 May-June; 9(3): 149-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952300&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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Early evaluation of tumour metabolic response using [18F]fluorodeoxyglucose and positron emission tomography: a pilot study following the phase II chemotherapy schedule for temozolomide in recurrent high-grade gliomas. Author(s): Brock CS, Young H, O'Reilly SM, Matthews J, Osman S, Evans H, Newlands ES, Price PM. Source: British Journal of Cancer. 2000 February; 82(3): 608-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10682673&dopt=Abstract
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Evaluation of temozolomide in a SCID mouse model of human B-cell precursor leukemia. Author(s): Messinger Y, Reaman GH, Ek O, Uckun FM. Source: Leukemia & Lymphoma. 1999 April; 33(3-4): 289-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10221508&dopt=Abstract
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Evaluation of the efficiency of chemotherapy in in vivo orthotopic models of human glioma cells with and without 1p19q deletions and in C6 rat orthotopic allografts serving for the evaluation of surgery combined with chemotherapy. Author(s): Branle F, Lefranc F, Camby I, Jeuken J, Geurts-Moespot A, Sprenger S, Sweep F, Kiss R, Salmon I.
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Source: Cancer. 2002 August 1; 95(3): 641-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209758&dopt=Abstract •
Experimental design and sample size determination for testing synergism in drug combination studies based on uniform measures. Author(s): Tan M, Fang HB, Tian GL, Houghton PJ. Source: Statistics in Medicine. 2003 July 15; 22(13): 2091-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820275&dopt=Abstract
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Immunophenotypical markers, ultrastructure and chemosensitivity profile of metastatic melanoma cells. Author(s): Prignano F, Coronnello M, Pimpinelli N, Cappugi P, Mini E, Giannotti B. Source: Cancer Letters. 2002 December 5; 186(2): 183-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12213288&dopt=Abstract
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Involvement of the mismatch repair system in temozolomide-induced apoptosis. Author(s): D'Atri S, Tentori L, Lacal PM, Graziani G, Pagani E, Benincasa E, Zambruno G, Bonmassar E, Jiricny J. Source: Molecular Pharmacology. 1998 August; 54(2): 334-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9687575&dopt=Abstract
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Irinotecan in the treatment of glioma patients: current and future studies of the North Central Cancer Treatment Group. Author(s): Buckner JC, Reid JM, Wright K, Kaufmann SH, Erlichman C, Ames M, Cha S, O'Fallon JR, Schaaf LJ, Miller LL. Source: Cancer. 2003 May 1; 97(9 Suppl): 2352-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712456&dopt=Abstract
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Irinotecan: promising activity in the treatment of malignant glioma. Author(s): Reardon DA, Friedman HS, Powell JB Jr, Gilbert M, Yung WK. Source: Oncology (Huntingt). 2003 May; 17(5 Suppl 5): 9-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800600&dopt=Abstract
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Laboratory and phase I studies of new cancer drugs. Author(s): Workman P, Kaye SB, Schwartsmann G. Source: Current Opinion in Oncology. 1992 December; 4(6): 1065-72. Review. Erratum In: Curr Opin Oncol 1993 March; 5(2): 434. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1360819&dopt=Abstract
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Late recurrence of a primitive neuro-ectodermal tumor. Author(s): Rao RD, Robins HI, Mehta MP.
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Source: Oncology. 2001; 61(3): 189-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11574773&dopt=Abstract •
New anticancer drugs in Europe. Author(s): Armand JP. Source: Gan to Kagaku Ryoho. 1997 May; 24 Suppl 1: 70-93. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9210890&dopt=Abstract
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New chemotherapeutic agents for breast cancer. Author(s): Abrams JS, Moore TD, Friedman M. Source: Cancer. 1994 August 1; 74(3 Suppl): 1164-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7913662&dopt=Abstract
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New chemotherapy options for the treatment of malignant gliomas. Author(s): Burton E, Prados M. Source: Current Opinion in Oncology. 1999 May; 11(3): 157-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10328588&dopt=Abstract
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New drugs in recurrent high grade gliomas. Author(s): Brandes AA, Pasetto LM, Monfardini S. Source: Anticancer Res. 2000 May-June; 20(3B): 1913-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10928126&dopt=Abstract
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Novel oral chemotherapy agents. Author(s): Royce ME, Hoff PM, Pazdur R. Source: Current Oncology Reports. 2000 January; 2(1): 31-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11122822&dopt=Abstract
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O6-benzylguanine-mediated enhancement of chemotherapy. Author(s): Friedman HS, Keir S, Pegg AE, Houghton PJ, Colvin OM, Moschel RC, Bigner DD, Dolan ME. Source: Molecular Cancer Therapeutics. 2002 September; 1(11): 943-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481416&dopt=Abstract
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Oligodendroglioma and anaplastic oligodendroglioma: clinical features, treatment, and prognosis. Author(s): Engelhard HH, Stelea A, Mundt A. Source: Surgical Neurology. 2003 November; 60(5): 443-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14572971&dopt=Abstract
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Pharmacokinetic considerations of oral chemotherapy in elderly patients with cancer. Author(s): Skirvin JA, Lichtman SM. Source: Drugs & Aging. 2002; 19(1): 25-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11929325&dopt=Abstract
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Phase I study of temozolomide and escalating doses of oral etoposide for adults with recurrent malignant glioma. Author(s): Korones DN, Benita-Weiss M, Coyle TE, Mechtler L, Bushunow P, Evans B, Reardon DA, Quinn JA, Friedman H. Source: Cancer. 2003 April 15; 97(8): 1963-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673724&dopt=Abstract
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Phase I. Trial of irinotecan and temozolomide in patients with solid tumors. Author(s): Jones SF, Gian VG, Greco FA, Miranda FT, Shipley DL, Thompson DS, Hainsworth JD, Toomey MA, Willcutt NT, Burris HA 3rd. Source: Oncology (Huntingt). 2003 May; 17(5 Suppl 5): 41-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800606&dopt=Abstract
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Phase II study of irinotecan (CPT-11) in children with high-risk malignant brain tumors: the Duke experience. Author(s): Turner CD, Gururangan S, Eastwood J, Bottom K, Watral M, Beason R, McLendon RE, Friedman AH, Tourt-Uhlig S, Miller LL, Friedman HS. Source: Neuro-Oncology. 2002 April; 4(2): 102-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11916501&dopt=Abstract
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Role of body surface area in dosing of investigational anticancer agents in adults, 1991-2001. Author(s): Baker SD, Verweij J, Rowinsky EK, Donehower RC, Schellens JH, Grochow LB, Sparreboom A. Source: Journal of the National Cancer Institute. 2002 December 18; 94(24): 1883-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488482&dopt=Abstract
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Schedule-dependent activity of temozolomide plus CPT-11 against a human central nervous system tumor-derived xenograft. Author(s): Patel VJ, Elion GB, Houghton PJ, Keir S, Pegg AE, Johnson SP, Dolan ME, Bigner DD, Friedman HS. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 October; 6(10): 4154-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11051270&dopt=Abstract
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Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972.
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Author(s): van den Bent MJ, Chinot O, Boogerd W, Bravo Marques J, Taphoorn MJ, Kros JM, van der Rijt CC, Vecht CJ, De Beule N, Baron B. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 April; 14(4): 599-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649108&dopt=Abstract •
Small-sample inference for incomplete longitudinal data with truncation and censoring in tumor xenograft models. Author(s): Tan M, Fang HB, Tian GL, Houghton PJ. Source: Biometrics. 2002 September; 58(3): 612-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12229996&dopt=Abstract
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Systemic chemotherapy for the treatment of metastatic melanoma. Author(s): Li Y, McClay EF. Source: Seminars in Oncology. 2002 October; 29(5): 413-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407507&dopt=Abstract
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Temozolomide in combination with docetaxel in patients with advanced melanoma: a phase II study of the Hellenic Cooperative Oncology Group. Author(s): Bafaloukos D, Gogas H, Georgoulias V, Briassoulis E, Fountzilas G, Samantas E, Kalofonos Ch, Skarlos D, Karabelis A, Kosmidis P. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 January 15; 20(2): 420-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11786569&dopt=Abstract
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Temozolomide in combination with other cytotoxic agents. Author(s): Prados M. Source: Seminars in Oncology. 2001 August; 28(4 Suppl 13): 24-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550136&dopt=Abstract
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The emerging role of irinotecan (CPT-11) in the treatment of malignant glioma in brain tumors. Author(s): Friedman HS, Keir ST, Houghton PJ. Source: Cancer. 2003 May 1; 97(9 Suppl): 2359-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712457&dopt=Abstract
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Therapeutic management of refractory or relapsed primary central nervous system lymphomas. Author(s): Reni M, Ferreri AJ. Source: Annals of Hematology. 2001; 80 Suppl 3: B113-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11757691&dopt=Abstract
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Use of temozolomide with other cytotoxic chemotherapy in the treatment of patients with recurrent brain metastases from lung cancer. Author(s): Ebert BL, Niemierko E, Shaffer K, Salgia R. Source: The Oncologist. 2003; 8(1): 69-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604733&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 TEMOZOLOMIDE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning temozolomide.
Recent Trials on Temozolomide The following is a list of recent trials dedicated to temozolomide.8 Further information on a trial is available at the Web site indicated. •
Biological Therapy and Temozolomide in Treating Patients With Metastatic Melanoma Condition(s): Stage IV Melanoma; Recurrent Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): St. Luke's Medical Center Purpose - Excerpt: RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining biological therapy with chemotherapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of biological therapy combined with temozolomide in treating patients who have metastatic melanoma. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00016055
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Gefitinib Plus Temozolomide in Treating Patients With Malignant Primary Glioma Condition(s): recurrent adult brain tumor; adult glioblastoma multiforme; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; Mixed Gliomas
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These are listed at www.ClinicalTrials.gov.
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Study Status: This study is currently recruiting patients. Sponsor(s): North American Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Biological therapies such as gefitinib may interfere with the growth of cancer cells and slow the growth of the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining gefitinib with chemotherapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining gefitinib with temozolomide in treating patients who have malignant primary glioma. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00027625 •
Irinotecan Plus Temozolomide in Treating Patients With Recurrent Primary Malignant Glioma Condition(s): recurrent adult brain tumor; adult glioblastoma multiforme; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; Mixed Gliomas Study Status: This study is currently recruiting patients. Sponsor(s): Duke Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of irinotecan plus temozolomide in treating patients who have recurrent primary malignant glioma. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005951
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Phase I/II Evaluation of Temozolomide and ZARNESTRA (R115777) for Recurrent and Progressive Glioblastoma Multiforme Condition(s): Glioblastoma Multiforme 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 find the highest safe dose of the new drug ZARNESTRA (R115777) and temozolomide that can be given to patients with brain tumors (glioblastoma multiforme, GBM). The second goal is to learn if these drugs given in combination can shrink or slow the growth of brain tumors. The safety of this treatment will also be studied. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00050986
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Temozolomide and Interferon alfa in Treating Patients With Stage III or Stage IV Melanoma Condition(s): iris melanoma; extraocular extension melanoma; recurrent intraocular melanoma; stage III melanoma; Stage IV Melanoma; Recurrent Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interferon alfa may interfere with the growth of cancer cells. Combining chemotherapy with interferon alfa may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining temozolomide and interferon alfa in treating patients who have stage III or stage IV melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00027742
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Temozolomide and O6-Benzylguanine for Treating Childhood Cancers Condition(s): Brain Neoplasm; Embryonal Neoplasm; Ewing's Sarcoma; Germ Gell Neoplasm; Liver Neoplasm; Nephroblastoma; Osteosarcoma; Rhabdomyosarcoma; Sarcoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: This study will investigate the combined use of temozolomide (TMZ) and O6-benzylguanine (O6BG) for treating cancer. TMZ is an anti-cancer drug approved to treat certain brain tumors in adults. TMZ loses its effectiveness over time because a protein called AGT makes the tumor resistant to the drug. O6BG inactivates AGT and, therefore, may prolong TMZ's effectiveness. Children and young adults under age 21 with various types of cancer (brain, liver, bone and others) for whom standard treatment was not successful may be eligible for this study. Participants will receive TMZ capsules by mouth and an intravenous (through a vein) infusion of O6BG 5 days in a row every month for up to 12 months. Blood will be drawn on days 3 and 5 of the first course of treatment to measure AGT levels. Also on day 5 of the first treatment course, 16 blood samples (1 teaspoon each) will be taken over a 48-hour period to study how the two drugs work in the body. If possible, a heparin lock will be placed in the vein to avoid having multiple needle sticks. A tissue biopsy (removal of a small piece of tumor) may be taken if the tumor is close to the skin and not near a vital organ. The sample will be used to evaluate the effect of O6BG on AGT levels. A doctor will see the patients weekly. Routine blood tests will be done twice a week. MRI or CT scans will be done before treatment begins and every 1 to 2 months during treatment to measure the size of the tumor. Patients with a brain tumor will also have a magnetic resonance spectroscopic test (similar to MRI) every 1 to 2 months to measure chemicals in the tumor. Patients will complete a Quality of Life Assessment questionnaire about the effect of the illness on the patient's behavior and everyday activities. Potential benefits to patients in this study are tumor shrinkage and symptom improvement, such as pain relief. Because this is an experimental therapy, however, the likelihood of tumor shrinkage cannot be predicted.
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Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005019 •
Temozolomide and O6-Benzylguanine in Treating Children With Recurrent Brain Tumors Condition(s): childhood brain tumor; childhood meningioma; childhood spinal cord tumors Study Status: This study is currently recruiting patients. Sponsor(s): Pediatric Brain Tumor Consortium; 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. O6-benzylguanine may increase the effectiveness of temozolomide by making tumor cells more sensitive to the drug. PURPOSE: Phase I trial to study the effectiveness of combining O6-benzylguanine with temozolomide in treating children who have recurrent or refractory brain tumors. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00052780
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Temozolomide and SCH66336 for Recurrent Glioblastoma Multiforme Condition(s): Glioblastoma Multiforme Study Status: This study is currently recruiting patients. Sponsor(s): M.D. Anderson Cancer Center Purpose - Excerpt: This study will combine the chemotherapy agent temozolomide with the investigational drug SCH66336 (an agent which interferes with new cell growth). Patients will be treated with oral temozolomide on days 1-5 and oral SCH66336 on days 8-28 every 28 days. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00038493
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Temozolomide and Thalidomide in Treating Patients With Metastatic, Locally Advanced, or Unresectable Leiomyosarcoma Condition(s): adult soft tissue sarcoma; uterine leiomyosarcoma; uterine sarcoma Study Status: This study is currently recruiting patients. Sponsor(s): Herbert Irving Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Combining temozolomide with
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thalidomide may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining temozolomide with thalidomide in treating patients who have metastatic, locally advanced, or unresectable leiomyosarcoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033709 •
Temozolomide and Vinorelbine in Treating Patients With Recurrent Brain Metastases Condition(s): brain metastases Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I/II trial to study the effectiveness of temozolomide and vinorelbine in treating patients who have recurrent brain metastases. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00026494
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Temozolomide Compared to Procarbazine, Lomustine, and Vincristine in Treating Patients With Recurrent Malignant Glioma Condition(s): adult glioblastoma multiforme; adult anaplastic astrocytoma; Mixed Gliomas; recurrent adult brain tumor Study Status: This study is currently recruiting patients. Sponsor(s): Medical Research Council Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which regimen of chemotherapy is more effective in treating recurrent malignant glioma. PURPOSE: Randomized phase III trial to compare the effectiveness of temozolomide alone to that of procarbazine, lomustine, and vincristine in treating patients who have recurrent malignant glioma. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00052455
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Temozolomide in Treating Patients With Mycosis Fungoides or Sezary Syndrome Condition(s): Cutaneous T-Cell Lymphoma; mycosis fungoides and Sezary syndrome Study Status: This study is currently recruiting patients. Sponsor(s): Robert H. Lurie Cancer Center; National Cancer Institute (NCI)
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Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of temozolomide in treating patients who have mycosis fungoides or Sezary syndrome 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/NCT00004106 •
Temozolomide in Treating Patients With Progressive Low-Grade Glioma Condition(s): adult brain tumor; childhood brain stem glioma; childhood brain tumor; childhood cerebral astrocytoma and malignant glioma; Childhood Oligodendroglioma; childhood visual pathway and hypothalamic glioma Study Status: This study is currently recruiting patients. Sponsor(s): Duke Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of temozolomide in treating patients with progressive low-grade glioma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003466
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Temozolomide in Treating Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Condition(s): gastrointestinal stromal tumor Study Status: This study is currently recruiting patients. Sponsor(s): Southwest Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of temozolomide in treating patients who have unresectable or metastatic gastrointestinal stromal tumors. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005597
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Temozolomide Plus Irinotecan in Treating Patients With Recurrent Malignant Glioma Condition(s): recurrent adult brain tumor; adult glioblastoma multiforme; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; Mixed Gliomas Study Status: This study is currently recruiting patients.
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Sponsor(s): North American Brain Tumor Consortium; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of temozolomide plus irinotecan in treating patients who have recurrent malignant glioma. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006025 •
Temozolomide Plus Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Malignant Glioma or Recurrent CNS or Other Solid Tumors Condition(s): Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Duke Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of temozolomide plus peripheral stem cell transplantation in treating children who have newly diagnosed malignant glioma or recurrent CNS tumors or other solid tumors. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005952
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Temozolomide Plus Radiation Therapy in Treating Patients With Newly Diagnosed Anaplastic Oligodendrogliomas or Mixed Anaplastic Oligoastrocytomas Condition(s): adult anaplastic oligodendroglioma; Mixed Gliomas Study Status: This study is currently recruiting patients. Sponsor(s): Radiation Therapy Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy and radiation therapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining temozolomide with radiation therapy in treating patients who have newly diagnosed anaplastic oligodendrogliomas or mixed anaplastic oligoastrocytomas. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033280
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Temozolomide, Thalidomide, and Celecoxib Following Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme Condition(s): Mixed Gliomas; adult glioblastoma multiforme Study Status: This study is currently recruiting patients. Sponsor(s): Dana-Farber/Harvard Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide and celecoxib may stop the growth of tumor cells by stopping blood flow to the tumor and may increase the effectiveness of temozolomide by making tumor cells more sensitive to the drug. PURPOSE: Phase II trial to study the effectiveness of combining temozolomide, thalidomide, and celecoxib following radiation therapy in treating patients who have newly diagnosed glioblastoma multiforme. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047294
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Temozolomide, Thalidomide, and Lomustine in Treating Patients With Unresectable Stage III or Stage IV Melanoma Condition(s): intraocular melanoma; Melanoma Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy, such as temozolomide and lomustine, use different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Combining temozolomide and thalidomide with lomustine may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining temozolomide and thalidomide with lomustine in treating patients who have unresectable stage III or stage IV melanoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00072345
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Carboplatin, Temozolomide, and Filgrastim in Treating Patients With Newly Diagnosed or Recurrent High-Grade Glioma Condition(s): adult brain stem glioma; adult glioblastoma multiforme; high-grade childhood cerebral astrocytoma; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma Study Status: This study is no longer recruiting patients. Sponsor(s): Kaplan Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or
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peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. PURPOSE: Phase II trial to study the effectiveness of combining carboplatin, temozolomide, and filgrastim in treating patients who have newly diagnosed or recurrent high-grade glioma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006263 •
Irinotecan Followed by Radiation Therapy and Temozolomide in Treating Children With Newly Diagnosed Brain Tumor Condition(s): high-grade childhood cerebral astrocytoma; untreated childhood brain stem glioma; untreated childhood cerebellar astrocytoma; Childhood Oligodendroglioma Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); St. Jude Children's Research Hospital Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of irinotecan followed by radiation therapy and temozolomide in treating children who have newly diagnosed brain tumor. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004068
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Radiation Therapy With or Without Temozolomide in Treating Patients With NonSmall Cell Lung Cancer That is Metastatic to the Brain Condition(s): brain metastases Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells. PURPOSE: Randomized phase II trial to compare the effectiveness of radiation therapy plus temozolomide to that of radiation therapy alone in treating patients who have non-small cell lung cancer that is metastatic to the brain. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00030836
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Temozolomide and O6-benzylguanine in Treating Patients With Newly Diagnosed, Recurrent, or Progressive Anaplastic Glioma Condition(s): recurrent adult brain tumor; adult glioblastoma multiforme; adult anaplastic astrocytoma; adult well-differentiated oligodendroglioma; adult anaplastic oligodendroglioma; Mixed Gliomas Study Status: This study is no longer recruiting patients. Sponsor(s): Duke Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining temozolomide and O6-benzylguanine in treating patients who have newly diagnosed, recurrent, or progressive anaplastic glioma. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006474
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Temozolomide and Thalidomide in Treating Patients With Stage III or Stage IV Melanoma Condition(s): intraocular melanoma; Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of melanoma by stopping blood flow to the tumor. Combining chemotherapy with thalidomide may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness temozolomide plus thalidomide in treating patients who have stage III or stage IV melanoma that cannot be removed during surgery. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005815
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Temozolomide Followed by Radiation Therapy in Treating Children With Newly Diagnosed Malignant CNS Tumors Condition(s): childhood brain tumor; childhood nerve tumor Study Status: This study is no longer recruiting patients. Sponsor(s): Duke Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Chemotherapy combined with radiation therapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of temozolomide followed by radiation therapy in treating children who have newly diagnosed malignant central nervous system tumors.
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Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005955 •
Temozolomide in Treating Patients With Brain Metastases Condition(s): brain metastases Study Status: This study is no longer recruiting patients. Sponsor(s): Duke Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of temozolomide in treating patients who have brain metastases. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005954
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Temozolomide in Treating Patients With Recurrent or Progressive Malignant Glioma Condition(s): recurrent adult brain tumor; adult anaplastic oligodendroglioma; adult anaplastic astrocytoma Study Status: This study is no longer recruiting patients. Sponsor(s): Herbert Irving Comprehensive Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of temozolomide in treating patients who have recurrent or progressive malignant glioma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004204
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Temozolomide plus PEG-Interferon alfa-2B in Treating Patients With Advanced Solid Tumors Condition(s): unspecified adult solid tumor, protocol specific Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Norris Cotton Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PEG-interferon alfa-2B may interfere with the growth of cancer cells. Combining temozolomide with PEG-interferon alfa-2B may be an effective treatment for advanced solid tumors. PURPOSE: Phase I trial to study the effectiveness of combining temozolomide and PEG-interferon alfa-2B in treating patients who have advanced solid tumors.
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Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00014261 •
Temozolomide With or Without Radiation Therapy to the Brain in Treating Patients With Stage IV Melanoma That Is Metastatic to the Brain Condition(s): Stage IV Melanoma; Recurrent Melanoma; brain metastases Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC Melanoma Cooperative Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known if chemotherapy is more effective with or without radiation therapy in treating brain metastases. PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy with or without radiation therapy to the brain in treating patients who have stage IV melanoma with asymptomatic brain metastases. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00020839
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Radiation Therapy Plus Thalidomide and Temozolomide in Treating Patients With Newly Diagnosed Brain Metastases Condition(s): brain metastases; unspecified adult solid tumor, protocol specific Study Status: This study is not yet open for patient recruitment. Sponsor(s): Comprehensive Cancer Center of Wake Forest University; 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. Radiation therapy uses high-energy x-rays to damage tumor cells. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Combining whole-brain radiation therapy with thalidomide and temozolomide may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining whole-brain radiation therapy with thalidomide and temozolomide in treating patients who have newly diagnosed brain metastases. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049361
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Study of Temozolomide in the Treatment of Brain Metastasis from Non-small-cell Lung Cancer Condition(s): Neoplasms
Metastases,
Neoplasm;
Carcinoma,
Non-Small-Cell
Lung;
Brain
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Study Status: This study is completed. Sponsor(s): Schering-Plough Purpose - Excerpt: Brain metastases from solid tumors are diagnosed in more than 300,000 patients annually. Nonsmall cell lung cancer accounts for the majority of CNS mets. Treatment with whole brain radiation and steroids will improve neurologic symptoms in about 50% of patients although survival is short. This study will test the safety and efficacy of temozolomide in combination with radiation therapy in the treatment of patients with brain mets form nonsmall cell lung cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00034697 •
Temozolomide and Radiation Therapy in Treating Patients With Stage IV Malignant Melanoma With Measurable and Unresectable Cancer Involving the Central Nervous System Condition(s): Stage IV Melanoma; Recurrent Melanoma; brain metastases Study Status: This study is not yet open for patient recruitment. Sponsor(s): North Central Cancer Treatment Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy, such as temozolomide, use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining temozolomide with radiation therapy may make the tumor cells more sensitive to radiation therapy and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining temozolomide with radiation therapy in treating patients who have stage IV malignant melanoma with measurable and unresectable cancer involving the central nervous system. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00068666
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Temozolomide and Thalidomide in Treating Patients With Brain Metastases Secondary to Melanoma Condition(s): Stage IV Melanoma; brain metastases; Recurrent Melanoma Study Status: This study is not yet open for patient recruitment. Sponsor(s): Cancer and Leukemia Group B; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy, such as temozolomide, use different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Combining temozolomide with thalidomide may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining temozolomide with thalidomide in treating patients who have brain metastases secondary to melanoma. Phase(s): Phase II
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00072163 •
Temozolomide in Treating Adults With Newly Diagnosed Primary Malignant Glioblastoma Multiforme Condition(s): Glioblastoma Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI); Duke Comprehensive Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of temozolomide in treating adults with newly diagnosed primary malignant glioblastoma multiforme. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003464
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Temozolomide in Treating Patients With Leptomeningeal Metastases From a Solid Tumor or Lymphoma Condition(s): leptomeningeal metastases Study Status: This study is completed. Sponsor(s): Norris Cotton 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. PURPOSE: Phase II trial to study the effectiveness of temozolomide in treating patients who have leptomeningeal metastases from a solid tumor or lymphoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005812
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Temozolomide in Treating Patients With Relapsed or Progressive Small Cell Lung Cancer Condition(s): Recurrent Small Cell Lung Cancer; intermediate type small cell lung cancer Study Status: This study is suspended. Sponsor(s): Fox Chase Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of temozolomide in treating patients who have relapsed or progressive small cell lung cancer. Phase(s): Phase II
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00022711 •
Temozolomide Plus Lomustine Followed by Radiation Therapy in Treating Patients With High-Grade Malignant Glioma Condition(s): high-grade childhood cerebral astrocytoma Study Status: This study is suspended. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining more than one chemotherapy drug with radiation therapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of temozolomide plus lomustine followed by radiation therapy in treating patients who have high-grade malignant glioma. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006024
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 “temozolomide” (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. PATENTS ON TEMOZOLOMIDE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “temozolomide” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on temozolomide, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Temozolomide By performing a patent search focusing on temozolomide, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on temozolomide: •
Cancer treatment with temozolomide Inventor(s): Ragab; Mohamed H. (Westfield, NJ) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 6,346,524 Date filed: March 27, 2000 Abstract: A method for treating a patient afflicted with cancer is provided, in which temozolomide is administered to the patient for at least two cycles of a cyclical dosing schedule, wherein each cycle has a dosing period of 5 to 25 days, in which temozolomide is administered daily, at a dose of 40 to 150 mg/m.sup.2 /day, followed by a rest period of 5 to 14 days in which temozolomide is not administered.Also provided is a medical kit for administering temozolomide, having printed instructions for administering temozolomide according to the cyclical dosing schedule set forth above, and a supply of temozolomide in dosage units for at least one cycle, wherein each dosage unit contains 5 to 250 mg of temozolomide and a pharmaceutically acceptable carrier. Excerpt(s): This invention relates to the treatment of cancer and in particular to the treatment of cancers with Temozolomide. Temozolomide is known for its anti-tumor effects. For example, in one study clinical responses were achieved in 17% of patients having advanced melanoma (Newlands et al. Br. J. Cancer 65 (2) 287-291 (1992)). In another study, a clinical response was achieved in 21% of patients with advanced melanoma (Journal of Clinical Oncology, Vol 13, No. 4 (April), 1995, pp 910-913). Treatment of gliomas in adults with temozolomide is also known (Eur. J. Cancer 1993; 29A:940). Treatment of the following cancers in adults with temozolomide has also been disclosed: metastatic melanoma; high grade glioma, glioblastoma and other brain cancers; lung cancer; breast cancer; testicular cancer; colon and rectal cancers; carcinomas; sarcomas; lymphomas; leukemias; and mycosis fungoides. Prior to the present invention, the generally accepted method for administering temozolomide was to administer it over a 28 day cycle, in which it is administered daily for the first 5 days of the cycle, followed by 23 days of rest, in which it is not administered. Newlands et al., Br. J. Cancer 65 (2) 287-291 (1992). A clinical trial has also been carried out wherein temozolomide was administered continuously as a daily dose for 6-7 weeks in conjunction with radiation treatment. See, e.g., Brock et al., Cancer Research 58, 43634367 (1998). The present invention provides a method for treating a patient afflicted with cancer, comprising administering temozolomide to said patient for at least two cycles of a cyclical dosing schedule, wherein each cycle comprises a dosing period of 5 to 25 days, in which temozolomide is administered daily, at a dose of 40 to 150 mg/m.sup.2 /day, followed by a rest period of 5 to 14 days in which temozolomide is not administered. Web site: http://www.delphion.com/details?pn=US06346524__
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•
Combination therapy for advanced cancer Inventor(s): Dugan; Margaret H. (Woodside, NY) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 5,824,346 Date filed: August 22, 1996 Abstract: There is disclosed a method for treating advanced cancer in patients in need of such treating. Temozolomide and cisplatin are administered in combination in amounts sufficient to achieve a clinical response. Excerpt(s): Despite the numerous advances in cancer treatment, the well-known life style changes that can greatly reduce the risk of cancer, and the early warning signs that some cancers provide, many patients still develop advanced cancer for which no conventional therapies are available that offer any reasonable hope of cure or significant palliation. This invention is the use of two known anti-tumor agents in combination therapy to provide a positive effect on such advanced cancers. It is also expected that the combination therapy will allow the administration of the two anti-tumor agents in quantities that will not result in intolerable side effects. Temozolomide is known for its anti-tumor effects. For example, in one study clinical responses were achieved in 17% of patients having advanced melanoma (Newlands ES, et al. Br J Cancer 65 (2) 287-2981, 1992). In another study a clinical response was achieved in 21% of patients with advanced melanoma (Journal of Clinical Oncology, Vol 13, No. 4 (April), 1995, pp 910913). However, temozolomide has dose-limiting side effects, such as hematologic toxicity, myelosuppression, anemia, leukopenia, etc. Cisplatin is known to have antitumor properties (see, for example B. Rosenberg et al. Nature 205, 698 (1965) and 222, 385 (1972). However, it too has dose-limiting side effects such as nephrotoxicity and ototoxicity. Web site: http://www.delphion.com/details?pn=US05824346__
•
Methods of using temozolomide in the treatment of cancers Inventor(s): Friedman; Henry S. (Durham, NC) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 6,251,886 Date filed: December 2, 1999 Abstract: Methods are disclosed for treating cancer in a patient in need of such treating comprising administering temozolomide in an amount effective to achieve a clinical response wherein the temozolomide is administered in a microcrystalline suspension. Excerpt(s): The present invention relates to methods of using microcrystalline compositions of temozolomide in the treatment of cancers, especially in the treatment of neoplastic meningitis and other cancers occurring in compartmentalized regions of the body such as the subarachnoid space. First recognized in 1870 (Eberth, C. J., Arch. Pathol. Anat. Physiol. Klin. Med., 49:51-63 (1870.), neoplastic meningitis is now being seen with increasing frequency, no doubt reflecting more effective therapy of systemic cancer as well as heightened awareness and improvements in diagnostic tools. Neoplastic meningitis can result from leptomeningeal dissemination of a spectrum of cancers, either arising from the central nervous system, such as medulloblastoma or high grade glioma, or resulting from invasion by lymphoma, leukemia, melanoma,
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sarcoma, or carcinoma (notably breast and lung carcinoma). Furthermore, the striking incidence in AIDS-related CNS lymphoma (which has a 50% incidence of leptomeningeal spread) suggests that an extensive population in the United States and abroad will require treatment of neoplastic meningitis. Unfortunately, current therapy of leptomeningeal disease is particularly ineffective with external beam radiotherapy and intrathecal chemotherapy, specifically methotrexate, thiotepa, or cytosine arabinoside only providing modest benefits, with mean survival following leptomeningeal tumor spread measured in months (Grossman S. A. and Moynihan T. J., Neurol. Clin., 9:843-856, 1991 1991). Newer therapies are clearly needed for treatment of patients with cancer, especially patients with neoplastic meningitis and other cancers occurring in compartmentalized regions of the body. The present invention provides methods of using microcrystalline compositions of temozolomide to treat cancer, especially neoplastic meningitis and other cancers occurring in compartmentalized regions of the body such as the subarachnoid space. In particular, the present invention provides a method for treating cancer in a patient in need of such treatment comprising administering temozolomide in an amount sufficient to achieve a clinical response, wherein the temozolomide is administered in a microcrystalline suspension. Web site: http://www.delphion.com/details?pn=US06251886__ •
Methoxyamine potentiation of temozolomide anti-cancer activity Inventor(s): Gerson; Stanton L. (Pepper Pike, OH), Liu; Lili (Euclid, OH) Assignee(s): Case Western Reserve University (Cleveland, OH) Patent Number: 6,465,448 Date filed: August 13, 1999 Abstract: This invention generally relates to novel compositions and methods for the treatment of certain cancers. Additionally, this invention relates to novel compositions and methods to screen drugs for the treatment of certain cancers. Specifically, the invention contemplates that temozolomide and methoxyamine, in combination or in sequence, shall be used as a treatment for certain tumors that are resistant to treatment by temozolomide alone. Excerpt(s): This invention generally relates to novel compositions and methods for the treatment of certain cancers. Additionally, this invention relates to novel compositions and methods to screen drugs useful for the treatment of certain cancers. Cancer is a worldwide problem. The American Cancer Society estimates that over one half million people will die from cancer in the United States alone in 1999. As such, finding novel compositions and methods for the treatment of cancer is of vital interest. The treatment of cancer falls into three general categories: chemotherapy, radiation therapy and surgery. Often, therapies are combined since a combination of therapies often increases the probability the cancer will be eradicated as compared to treatment strategies utilizing a single therapy. Most typically, the surgical excision of large tumor masses is followed by chemotherapy and/or radiation therapy. Chemotherapeutic agents can work in a number of ways. For example, chemotherapeutic can work by interfering with cell cycle progression or by generating DNA strand breaks. If the cancer cell is not able to overcome the cell cycle blockage or cell injury caused by the therapeutic compound, the cell will often die via apoptotic mechanisms. The use of a single chemotherapeutic agent in the treatment of cancer, with or without surgery or radiation, has several disadvantages. First, the cells may develop resistance to the chemotherapeutic agent. Such resistance results either in the requirement for higher dosages of the drug and/or
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the renewed spread of the cancer. Chemotherapeutic agents can be toxic to the patient. Therefore, there is a practical upper limit to the amount that a patient can receive. However, if two chemotherapeutic agents are used in concert, the dosage of any single drug can be lowered. This is beneficial to the patient since using lower levels of chemotherapeutic agents is generally safer for the patient. Additionally, cancer cells are less likely to generate resistance to the combination of drugs as they are to a single drug. Web site: http://www.delphion.com/details?pn=US06465448__ •
Potentiation of temozolomide in human tumour cells Inventor(s): Baer; John Colin (London, GB2), Freeman; Azadeh Alison (Croydon, GB2), Margison; Geoffrey Paul (Poynton, GB2), Newlands; Edward Stuart (London, GB2), Rafferty; Joseph Anthony (Edgeley Stockport, GB2), Watson; Amanda Jean (Godley Hyde, GB2) Assignee(s): Cancer Research Campaign Technology (Regent's Park, GB2) Patent Number: 5,731,304 Date filed: June 7, 1995 Abstract: The toxicity of temozolomide, an anti-tumour agent useful in the treatment of various mammalian neoplasms, can be potentiated by the prior administration of an ATase inhibiting agent, i.e., O.sup.6 -benzylguanine. Excerpt(s): Temozolomide, or 8-carbamoyl-3-methylimidazo›5,1-d!-1,2,3,5,-tetrazin-4(3H)-one, (CCRG 81045, NSC 362856) has been found to possess valuable antitumour properties, see Newlands et al., Br. J. Cancer, 65: 287 (1992). In the clinic, temozolomide has shown activity against astrocytoma, gliomas, malignant melanoma and mycosis fungoides. The drug is most useful when administered according to a repeat dose schedule. Methylated O.sup.6 -alkylguanine, e.g., from reaction with MTIC (the active methylating species of temozolomide), is repaired by the protein O.sup.6 -alkylguanine DNA alkyltransferase (ATase). Pretreatment of ATase-expressing cells with methylating agents (e.g., Zlotogoski et al., Carcinogenesis, 5:83, 1984; Gibson et el., Cancer Res., 46:4995, 1986), O.sup.6 -methylguanine (e.g., Dolan et al., Biophys. Res. Commun., 132:178 1985) or O.sup.6 -benzylguanine (O.sup.6 -BG, Dolan et al., Proc. Natl. Acad. Sci. U.S.A., 87:5368, 1990) has thus been shown to increase the cytotoxic effects of chloroethylating agents whilst little or no sensitization was observed in cells that do not express ATase. Moschel, Dolan and Pegg, in U.S. Pat. No. 5,091,430, note that a transient decrease in ATase activity is all that is needed to enhance the effectiveness of chloroethylating agents. PCT published Application WO 91/13898 notes, for instance, a 3.8 fold decrease in the ED.sub.50 for Me CCNU when combined with O.sup.6 benzylguanine in SF767 cells. Thus, Moschel et al. show a general enhancement of the anti-neoplastic activity of an alkylating agent when used with a depletor of alkyltransferase. Web site: http://www.delphion.com/details?pn=US05731304__
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Patent Applications on Temozolomide As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to temozolomide: •
Combination therapy (temozolomide and alpha-IFN) for advanced cancer Inventor(s): Dugan, Margaret H.; (Woodside, NY) Correspondence: Schering-plough Corporation; Patent Department (k-6-1, 1990); 2000 Galloping Hill Road; Kenilworth; NJ; 07033-0530; US Patent Application Number: 20020172662 Date filed: April 26, 2002 Abstract: There is disclosed a method for treating advanced cancer in patients in need of such treating. Temozolomide and alpha interferon are administered in combination in amounts sufficient to achieve a clinical response. Excerpt(s): Despite the numerous advances in cancer treatment, the well-known life style changes that can greatly reduce the risk of cancer, and the early warning signs that some cancers provide, many patients still develop advanced cancer for which no conventional therapies are available that offer any reasonable hope of cure or significant palliation. This invention is the use of two known anti-tumor agents in combination therapy to provide a positive effect on such advanced cancers. It is also expected that the combination therapy will allow the administration of the two anti-tumor agents in quantities that will not result in intolerable side effects. Temozolomide is known for its anti-tumor effects. For example, in one study clinical responses were achieved in 17% of patients having advanced melanoma (Newlands ES, et al. Br J Cancer 65 (2) 287-2981, 1992). In another sudy a clinical response was achieved in 21% of patients with advanced melanoma (Journal of Clinical Oncology, Vol 13, No. 4 (April), 1995, pp 910913). However, temozolomide is not always effective and has dose-limiting side effects, such as hematologic toxicity, myelosuppression, anemia, leukopenia, etc. Alpha interferon is also known to have anti-cancer effects. See, for example, Ernstoff et al., Intravenous (IV) Recombinant.alpha.-2 Interferon in Metastatic Melanoma, Proc ASCO 2:57 (C-222), 1983. However this treatment is not always effective and sometimes results in intolerable side effects related to the dosage and duration of therapy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Combination therapy for cancer Inventor(s): Zaknoen, Sara L.; (Hoboken, NJ) Correspondence: Schering-plough Corporation; Patent Department (k-6-1, 1990); 2000 Galloping Hill Road; Kenilworth; NJ; 07033-0530; US Patent Application Number: 20020009428 Date filed: January 22, 2001 Abstract: A method for treating a human patient afflicted with cancer, is provided in which therapeutically effective amounts of temozolomide and pegylated interferon
10
This has been a common practice outside the United States prior to December 2000.
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alpha are administered to such a patient. Also provided is a medical kit comprising:(a) a supply of temozolomide;(b) a supply of pegylated interferon alpha; and(c) printed instructions for administering temozolomide and pegylated interferon alpha to a cancer patient. Excerpt(s): Despite the numerous advances in cancer treatment, the well-known life style changes that can greatly reduce the risk of cancer, and the early warning signs that some cancers provide, many patients still develop cancer for which no conventional therapies are available that offer any reasonable hope of cure or significant palliation. Temozolomide is known for its anti-tumor effects. For example, in one study clinical responses were achieved in 17% of patients having advanced melanoma (Newlands E S, et al., Br J Cancer 65 (2) 287-291, 1992). In another study, a clinical response was achieved in 21 % of patients with advanced melanoma (Journal of Clinical Oncology, Vol. 13, No. 4 (April), 1995, pp. 910-913). However, temozolomide is not always effective and has dose-limiting side effects, such as hematologic toxicity, myelosuppression, anemia, leukopenia, etc. Interferon alpha is also known to have anticancer effects. See, for example, Ernstoff et al., Intravenous (IV) Recombinant.alpha.-2 Interferon in Metastatic Melanoma, Proc ASCO 2:57 (C-222), 1983. However, this treatment is not always effective and sometimes results in intolerable side effects related to the dosage and duration of therapy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions and methods for the treatment of cancer Inventor(s): Hwu, Wen-Jen; (New York, NY) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20020128228 Date filed: November 30, 2001 Abstract: This invention relates to compositions comprising temozolomide and thalidomide which can be used in the treatment or prevention of cancer, in particular malignant melanoma, cancer of the skin, subcutaneous tissue, lymph nodes, brain, lung, liver, bone, intestine, colon, heart, pancreas, adrenals, kidney, prostate, breast, colorectal, or a combination thereof. A particular composition comprises temozolomide, or a pharmaceutically acceptable salt, solvate, or clathrate thereof, and thalidomide, or a pharmaceutically acceptable salt, solvate, or clathrate thereof. The invention also relates to methods of treating or preventing cancer, in particular malignant melanoma, cancer of the skin, subcutaneous tissue, lymph nodes, brain, lung, liver, bone, intestine, colon, heart, pancreas, adrenals, kidney, prostate, breast, colorectal, or a combination thereof, which comprise the administration of temozolomide and thalidomide and another anticancer drug to a patient in need of such treatment or prevention. The invention further relates to methods of reducing or avoiding adverse side effects associated with the administration of cancer chemotherapy or radiation therapy which comprise the administration of temozolomide and thalidomide to a patient in need of such reduction or avoidance. Excerpt(s): This application claims priority to U.S. Provisional Application Serial No. 60/250,130 filed Dec. 1, 2000 which is hereby incorporated by reference. This invention relates to methods of treating primary and metastatic cancer, in particular malignant melanoma, and cancer of the skin, subcutaneous tissue, lymph nodes, brain, lung, liver,
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bone, intestine, colon, heart, pancreas, adrenals, kidney, prostate and breast, and to methods of reducing or avoiding adverse effects associated with anti-cancer agents such as temozolomide using thalidomide as adjunctive therapy. The invention also relates to pharmaceutical compositions and kits comprising temozolomide and thalidomide for use in combination therapy. The incidence of cancer continues to climb as the general population ages, as new cancers develop, and as susceptible populations (e.g., people infected with AIDS or excessively exposed to sunlight) grow. A tremendous demand therefore exists for new methods and compositions that can be used to treat patients with cancer. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methoxyamine combinations in the treatment of cancer Inventor(s): Gerson, Stanton L.; (Pepper Pike, OH), Liu, Lili; (Euclid, OH) Correspondence: Medlen & Carroll, Llp; 101 Howard Street, Suite 350; San Francisco; CA; 94105; US Patent Application Number: 20020198264 Date filed: February 19, 2002 Abstract: This invention generally relates to novel compositions and methods for the treatment of certain cancers. Additionally, this invention relates to novel compositions and methods to screen drugs for the treatment of certain cancers. Specifically, the invention contemplates that temozolomide and methoxyamine, in combination or in sequence, shall be used as a treatment for certain tumors that are resistant to treatment by temozolomide alone. Additionally, methoxyamine is contemplated for methods of treatment of cancer, wherein methoxyamine is used, in combination or in sequence, with other anticancer drugs or agents. Excerpt(s): This invention generally relates to novel compositions and methods for the treatment of certain cancers. Additionally, this invention relates to novel compositions and methods to screen drugs useful for the treatment of certain cancers. Cancer is a worldwide problem. The American Cancer Society estimates that over one half million people will die from cancer in the United States alone in 1999. As such, finding novel compositions and methods for the treatment of cancer is of vital interest. The treatment of cancer falls into three general categories: chemotherapy, radiation therapy and surgery. Often, therapies are combined since a combination of therapies often increases the probability the cancer will be eradicated as compared to treatment strategies utilizing a single therapy. Most typically, the surgical excision of large tumor masses is followed by chemotherapy and/or radiation therapy. Chemotherapeutic agents can work in a number of ways. For example, chemotherapeutic can work by interfering with cell cycle progression or by generating DNA strand breaks. If the cancer cell is not able to overcome the cell cycle blockage or cell injury caused by the therapeutic compound, the cell will often die via apoptotic mechanisms. The use of a single chemotherapeutic agent in the treatment of cancer, with or without surgery or radiation, has several disadvantages. First, the cells may develop resistance to the chemotherapeutic agent. Such resistance results either in the requirement for higher dosages of the drug and/or the renewed spread of the cancer. Chemotherapeutic agents can be toxic to the patient. Therefore, there is a practical upper limit to the amount that a patient can receive. However, if two chemotherapeutic agents are used in concert, the dosage of any single drug can be lowered. This is beneficial to the patient since using lower levels of
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chemotherapeutic agents is generally safer for the patient. Additionally, cancer cells are less likely to generate resistance to the combination of drugs as they are to a single drug. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Synthesis of temozolomide and analogs Inventor(s): Hou, Donald; (Newtown, PA), Kuo, Shen-Chun; (Union, NJ), Mas, Janet L.; (Green Brook, NJ) Correspondence: Schering-plough Corporation; Patent Department (k-6-1, 1990); 2000 Galloping Hill Road; Kenilworth; NJ; 07033-0530; US Patent Application Number: 20020095036 Date filed: January 16, 2002 Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/262,465 filed Jan. 18, 2001. This invention relates to a novel process for the synthesis of Temozolomide, an antitumor compound, and analogs, and to intermediates useful in this novel process. It is described in U.S. Pat. No. 5,260,291 (Lunt et al.) together with compounds of broadly similar activity such as higher alkyl analogs at the 3-position. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with temozolomide, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “temozolomide” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on temozolomide. You can also use this procedure to view pending patent applications concerning temozolomide. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 6. PERIODICALS AND NEWS ON TEMOZOLOMIDE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover temozolomide.
News Services and Press Releases One of the simplest ways of tracking press releases on temozolomide 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 “temozolomide” (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 temozolomide. 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 “temozolomide” (or synonyms). The following was recently listed in this archive for temozolomide: •
Temozolomide plus cisplatin "interesting" for recurrent glioma Source: Reuters Industry Breifing Date: October 21, 2002
•
Temozolomide improves response of brain metastases to radiation therapy Source: Reuters Medical News Date: October 08, 2002
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•
Temozolomide plus thalidomide well tolerated in melanoma patients Source: Reuters Industry Breifing Date: June 14, 2002
•
Temozolomide shows promise in treatment of anaplastic oligodendroglioma Source: Reuters Industry Breifing Date: July 27, 2001
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Temozolomide may prolong life in patients with relapsed malignant astrocytomas Source: Reuters Medical News Date: August 31, 1999
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Schering-Plough's temozolomide approved in EU Source: Reuters Medical News Date: August 27, 1999
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FDA approves temozolomide for refractory anaplastic astrocytoma Source: Reuters Medical News Date: August 12, 1999
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Schering-Plough gets EU panel recommendation for temozolomide Source: Reuters Medical News Date: May 27, 1999
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Temozolomide prolongs progression-free survival in patient with glioblastoma multiforme Source: Reuters Medical News Date: May 18, 1999
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Schering-Plough submits additional application for temozolomide in EU Source: Reuters Medical News Date: March 31, 1999
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FDA advisers vote against approval of temozolomide for metastatic melanoma Source: Reuters Medical News Date: March 24, 1999
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FDA advisers say temozolomide approvable for anaplastic astrocytoma Source: Reuters Medical News Date: January 13, 1999
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Temozolomide prolongs survival in subset of patients with glioblastomas or astrocytomas Source: Reuters Medical News Date: September 16, 1998
•
Schering-Plough submits NDA for anti-tumor drug temozolomide Source: Reuters Medical News Date: August 19, 1998 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
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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 “temozolomide” (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 you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “temozolomide” (or synonyms). If you know the name of a company that is relevant to temozolomide, 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 “temozolomide” (or synonyms).
Academic Periodicals covering Temozolomide Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to temozolomide. In addition to these sources, you can search for articles covering temozolomide 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.”
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If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 7. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for temozolomide. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with temozolomide. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to temozolomide: Temozolomide •
Systemic - U.S. Brands: Temodar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500076.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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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 Institute11: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
•
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/
11
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.12 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:13 •
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/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
12
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). 13 See http://www.nlm.nih.gov/databases/databases.html.
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•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “temozolomide” (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 405 1 58 2 0 466
HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “temozolomide” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
14
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
15
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). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18
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 Biologists19 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.20 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.21 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/.
19 Adapted 20
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. 21 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 temozolomide 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 temozolomide. 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 temozolomide. 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 “temozolomide”:
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•
Other guides Bone Cancer http://www.nlm.nih.gov/medlineplus/bonecancer.html Brain Cancer http://www.nlm.nih.gov/medlineplus/braincancer.html Cancer http://www.nlm.nih.gov/medlineplus/cancer.html Kidney Transplantation http://www.nlm.nih.gov/medlineplus/kidneytransplantation.html Soft Tissue Sarcoma http://www.nlm.nih.gov/medlineplus/softtissuesarcoma.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 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 temozolomide. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
•
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/
Patient Resources
•
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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 temozolomide. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with temozolomide. 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 temozolomide. 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 “temozolomide” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “temozolomide”. 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 “temozolomide” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.
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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 “temozolomide” (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.22
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
22
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)23: •
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)
•
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
•
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/
•
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
•
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/
23
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries
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•
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
•
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
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
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
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
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
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
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
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
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
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•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
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/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
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
115
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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TEMOZOLOMIDE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 9-cis retinoic acid: A drug being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]
Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]
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 antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU]
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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] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [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] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]
Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Allografts: A graft of tissue obtained from the body of another animal of the same species but with genotype differing from that of the recipient; tissue graft from a donor of one genotype to a host of another genotype with host and donor being members of the same species. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] 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] 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
Dictionary 119
pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] 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] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anterior chamber: The space in front of the iris and behind the cornea. [NIH] Antiangiogenic: Having to do with reducing the growth of new blood vessels. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH]
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Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]
Antitumour: Counteracting tumour formation. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [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] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located
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in the basal regions of the cerebral hemispheres. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Binding agent: A substance that makes a loose mixture stick together. For example, binding agents can be used to make solid pills from loose powders. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] 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
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is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] 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] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain metastases: Cancer that has spread from the original (primary) tumor to the brain. [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]
Buprenorphine: A derivative of the opioid alkaloid thebaine that is a more potent and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase.
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Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Carmustine: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH]
Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [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] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell 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 membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU]
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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] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the
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high content of polar groups which are responsible for its swelling properties. [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] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete 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,
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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] Concomitant: Accompanying; accessory; joined with another. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consolidation: The healing process of a bone fracture. [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] Contralateral: Having to do with the opposite side of the body. [NIH] Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] 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] Curative: Tending to overcome disease and promote recovery. [EU] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cystitis: Inflammation of the urinary bladder. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [NIH]
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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] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dacarbazine: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] 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] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [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] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] 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] Dihydrotestosterone: Anabolic agent. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [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] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity
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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] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] 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] 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] Enhancer: Transcriptional element in the virus genome. [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]
Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Exocrine: Secreting outwardly, via a duct. [EU]
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External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extraocular: External to or outside of the eye. [NIH] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fenretinide: A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Filgrastim: A colony-stimulating factor that stimulates the production of neutrophils (a type of white blood cell). It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called granulocyte colony-stimulating factor (G-CSF). [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in
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carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Fold: A plication or doubling of various parts of the body. [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] 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] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [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 Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels. [NIH] Gene-modified: Cells that have been altered to contain different genetic material than they originally contained. [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] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] 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] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH]
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Glioblastoma multiforme: A type of brain tumor that forms from glial (supportive) tissue of the brain. It grows very quickly and has cells that look very different from normal cells. Also called grade IV astrocytoma. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] 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] Granulocyte Colony-Stimulating Factor: A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. [NIH] 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] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [NIH] Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH]
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Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Histone Deacetylase: Hydrolyzes N-acetyl groups on histones. [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] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] 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] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH]
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Ifosfamide: Positional isomer of cyclophosphamide which is active as an alkylating agent and an immunosuppressive agent. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [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] Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] 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 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] 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
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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 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] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] 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-2b: A recombinant alfa interferon consisting of 165 amino acid residues with arginine in position 23 and histidine in 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] 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] Intracranial tumors: Tumors that occur in the brain. [NIH] Intraocular: Within the eye. [EU] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intrathecal chemotherapy: Anticancer drugs that are injected into the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. [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
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or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irinotecan: An anticancer drug that belongs to a family of anticancer drugs called topoisomerase inhibitors. It is a camptothecin analogue. Also called CPT 11. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] 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] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Jurkat Cells: A cell line derived from human T-cell leukemia and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation. [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] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [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] Leptomeningeal metastases: Cancer that has spread from the original (primary) tumor to
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the tissues that cover the brain and spinal cord. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [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] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [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] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lomustine: An alkylating agent of value against both hematologic malignancies and solid tumors. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] 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] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of
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radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant mesothelioma: A rare type of cancer in which malignant cells are found in the sac lining the chest or abdomen. Exposure to airborne asbestos particles increases one's risk of developing malignant mesothelioma. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Marimastat: An anticancer drug that belongs to the family of drugs called angiogenesis inhibitors. Marimastat is a matrix metalloproteinase inhibitor. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Maximum Tolerated Dose: The highest dose level eliciting signs of toxicity without having major effects on survival relative to the test in which it is used. [NIH] Mechlorethamine: A vesicant and necrotizing irritant destructive to mucous membranes. It was formerly used as a war gas. The hydrochloride is used as an antineoplastic in Hodgkin's disease and lymphomas. It causes severe gastrointestinal and bone marrow damage. [NIH] Medical Oncology: A subspecialty of internal medicine concerned with the study of neoplasms. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medulloblastoma: A malignant brain tumor that begins in the lower part of the brain and can spread to the spine or to other parts of the body. Medulloblastomas are sometimes called primitive neuroectodermal tumors (PNET). [NIH] 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] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningioma: A type of tumor that occurs in the meninges, the membranes that cover and protect the brain and spinal cord. Meningiomas usually grow slowly. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH]
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Mesothelioma: A benign (noncancerous) or malignant (cancerous) tumor affecting the lining of the chest or abdomen. Exposure to asbestos particles in the air increases the risk of developing malignant mesothelioma. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastasize: To spread from one part of the body to another. When cancer cells metastasize and form secondary tumors, the cells in the metastatic tumor are like those in the original (primary) tumor. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Metastatic cancer: Cancer that has spread from the place in which it started to other parts of the body. [NIH] Methyltransferase: A drug-metabolizing enzyme. [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] 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] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [NIH]
Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus
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surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Motility: The ability to move spontaneously. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagenicity: Ability to damage DNA, the genetic material; the power to cause mutations. [NIH]
Mycosis: Any disease caused by a fungus. [EU] Mycosis Fungoides: A chronic malignant T-cell lymphoma of the skin. In the late stages the lymph nodes and viscera are affected. [NIH] Myelin: The fatty substance that covers and protects nerves. [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] Myelotoxic: 1. Destructive to bone marrow. 2. Arising from diseased bone marrow. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [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] 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] Neoplastic meningitis: Tumor cells that have spread from the original (primary) tumor to the tissue that covers the brain, spinal cord, or both. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU]
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Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitrosoureas: A group of anticancer drugs that can cross the blood-brain barrier. Carmustine and lomustine are nitrosoureas. [NIH] Nonmalignant: Not cancerous. [NIH] Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [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] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oligodendroglial: A cell that lays down myelin. [NIH] Oligodendroglial tumors: Rare, slow-growing tumors that begin in brain cells called oligodendrocytes, which provide support and nourishment for cells that transmit nerve impulses. Also called oligodendroglioma. [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] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. [NIH] Oncology: The study of cancer. [NIH] Ophthalmic: Pertaining to the eye. [EU] Overexpress: An excess of a particular protein on the surface of a cell. [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]
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Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [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] 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] Particle: A tiny mass of material. [EU] 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] Performance status: A measure of how well a patient is able to perform ordinary tasks and carry out daily activities. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral stem cell transplantation: A method of replacing blood-forming cells destroyed by cancer treatment. Immature blood cells (stem cells) in the circulating blood that are similar to those in the bone marrow are given after treatment to help the bone marrow recover and continue producing healthy blood cells. Transplantation may be autologous (an individual's own blood cells saved earlier), allogeneic (blood cells donated by someone else), or syngeneic (blood cells donated by an identical twin). Also called peripheral stem cell support. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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] Phenylbutyrate: An anticancer drug that belongs to the family of drugs called differentiating agents. [NIH]
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Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photosensitizer: A drug used in photodynamic therapy. When absorbed by cancer cells and exposed to light, the drug becomes active and kills the cancer cells. [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]
Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [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] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] 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] 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] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [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
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sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] 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] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiate: 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] 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] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Primary central nervous system lymphoma: Cancer that arises in the lymphoid tissue found in the central nervous system (CNS). The CNS includes the brain and spinal cord. [NIH]
Primary tumor: The original tumor. [NIH] Primitive neuroectodermal tumors: PNET. A type of bone cancer that forms in the middle (shaft) of large bones. Also called Ewing's sarcoma/primitive neuroectodermal tumor. [NIH] Procarbazine: An antineoplastic agent used primarily in combination with mechlorethamine, vincristine, and prednisone (the MOPP protocol) in the treatment of Hodgkin's disease. [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]
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Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein 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] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] 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]
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]
Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH]
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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 oncologist: A doctor who specializes in using radiation to treat cancer. [NIH] Radiation Oncology: A subspecialty of medical oncology and radiology concerned with the radiotherapy of cancer. [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] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] 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] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] 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] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU]
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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 cell cancer: Cancer that develops in the lining of the renal tubules, which filter the blood and produce urine. [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] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [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] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] 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] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal,
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excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] 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] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senescence: The bodily and mental state associated with advancing age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [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] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Silicon Dioxide: Silica. Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, quartz, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of
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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] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] 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] Spectrometer: An apparatus for determining spectra; measures quantities such as wavelengths and relative amplitudes of components. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] 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] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Steady state: Dynamic equilibrium. [EU] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroids: Drugs used to relieve swelling and inflammation. [NIH]
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Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [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] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supratentorial: Located in the upper part of the brain. [NIH] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] 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] Synthetic retinoid: A substance related to vitamin A that is produced in a laboratory. [NIH] Systemic: Affecting the entire body. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Temozolomide: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH]
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Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thiotepa: A very toxic alkylating antineoplastic agent also used as an insect sterilant. It causes skin, gastrointestinal, CNS, and bone marrow damage. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), thiotepa may reasonably be anticipated to be a carcinogen (Merck Index, 11th ed). [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] 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
Dictionary 151
and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [NIH] Topotecan: An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerase. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translating: Conversion from one language to another language. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] 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]
Tumor model: A type of animal model which can be used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor-derived: Taken from an individual's own tumor tissue; may be used in the development of a vaccine that enhances the body's ability to build an immune response to the tumor. [NIH]
152 Temozolomide
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] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Unresectable: Unable to be surgically removed. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [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] 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] Vertebrae: A bony unit of the segmented spinal column. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Vinorelbine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] 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]
Dictionary 153
Vivo: Outside of or removed from the body of a living organism. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
155
INDEX 9 9-cis retinoic acid, 9, 117 A Abdomen, 117, 122, 128, 134, 135, 136, 137, 138, 141, 149, 152 Abdominal, 117, 127, 141 Acceptor, 117, 140, 150 Acute leukemia, 36, 117 Adaptability, 117, 123 Adduct, 5, 117 Adenine, 5, 117, 144 Adenocarcinoma, 117, 140 Adenosine, 40, 117, 122, 150 Adenovirus, 7, 26, 117 Adjunctive Therapy, 88, 117 Adjuvant, 5, 19, 21, 40, 117 Adjuvant Therapy, 5, 117 Adverse Effect, 88, 117, 147 Affinity, 117, 118, 120 Agonist, 118, 122 Albumin, 118, 142 Algorithms, 118, 121 Alkaloid, 118, 122, 139, 150 Alkylating Agents, 4, 6, 18, 33, 118, 123, 127, 149 Allergen, 118, 147 Allogeneic, 10, 118, 131, 141 Allografts, 59, 118 Alopecia, 118, 126 Alpha Particles, 118, 145 Alternative medicine, 93, 118 Amino Acid Sequence, 118, 119 Amino Acids, 118, 141, 143, 144 Anaesthesia, 118, 133 Analgesic, 119, 122, 139 Analog, 5, 119, 130 Anaplastic, 4, 13, 30, 32, 42, 61, 65, 66, 69, 70, 71, 72, 74, 75, 92, 119 Anemia, 83, 86, 87, 119, 150 Angiogenesis, 35, 55, 119, 137 Angiogenesis inhibitor, 35, 55, 119, 137 Animal model, 10, 15, 119, 151 Anions, 118, 119, 135 Anterior chamber, 119, 135 Antiangiogenic, 12, 119 Antibacterial, 119, 148 Antibiotic, 119, 148 Antibodies, 8, 119, 133, 136, 142, 145
Antibody, 117, 119, 125, 132, 133, 135, 138, 145, 147, 153 Anticoagulant, 119, 144 Antifungal, 119, 135 Antigen, 34, 117, 119, 125, 132, 133, 147 Anti-inflammatory, 119, 123, 143 Anti-Inflammatory Agents, 119, 123 Antineoplastic, 15, 42, 118, 120, 123, 126, 129, 134, 137, 141, 142, 143, 150, 151, 152 Antineoplastic Agents, 15, 118, 120, 152 Antitumour, 25, 85, 120 Antiviral, 120, 134 Anus, 120, 122, 145 Apoptosis, 7, 11, 19, 31, 48, 51, 54, 60, 120, 123 Aqueous, 120, 121, 127 Arginine, 120, 134 Arterial, 35, 58, 120, 144 Arteries, 120, 121, 126, 138 Asbestos, 120, 137, 138 Astrocytes, 20, 120 Astrocytoma, 4, 30, 32, 65, 66, 69, 70, 72, 73, 74, 75, 79, 85, 92, 120, 130, 131 Asymptomatic, 76, 120 Autologous, 10, 120, 141 B Bacteria, 119, 120, 129, 138, 148, 151, 152 Bacteriophage, 120, 151 Barbiturate, 120, 150 Basal Ganglia, 120, 130 Base, 4, 5, 11, 19, 29, 51, 117, 121, 127, 135 Basement Membrane, 121, 129 Benign, 121, 138, 139, 145 Bile, 121, 130, 136 Binding agent, 11, 121 Bioavailability, 16, 28, 121 Biochemical, 5, 11, 15, 25, 48, 54, 58, 121 Biological response modifier, 121, 134 Biological therapy, 65, 121 Biopsy, 67, 121 Biotechnology, 20, 21, 93, 101, 121 Bladder, 121, 126, 144, 152 Blood pressure, 121, 138 Blood vessel, 119, 121, 122, 128, 131, 136, 147, 148, 149, 150, 152 Blood-Brain Barrier, 9, 121, 140
156 Temozolomide
Bone Marrow, 32, 34, 72, 117, 121, 122, 131, 133, 136, 137, 138, 139, 141, 148, 149, 150 Bone Marrow Cells, 34, 122, 137 Bone scan, 122, 146 Bowel, 19, 122, 127, 134 Bowel Movement, 122, 127 Brachytherapy, 122, 134, 135, 145, 153 Bradykinin, 122, 142 Brain metastases, 17, 23, 37, 38, 45, 47, 50, 51, 58, 64, 69, 73, 75, 76, 77, 91, 122 Brain Stem, 70, 72, 73, 122, 124 Brain stem glioma, 70, 72, 73, 122 Branch, 113, 122, 136, 141, 148, 150 Buprenorphine, 16, 122 C Caffeine, 122, 144 Calcium, 120, 122, 125, 137, 147 Camptothecin, 7, 122, 135 Capsules, 67, 123 Carboplatin, 58, 72, 73, 123 Carcinogen, 117, 123, 150 Carcinogenic, 118, 123, 134, 144 Carcinoma, 18, 58, 76, 84, 123, 140, 148 Carmustine, 17, 123, 140 Carrier Proteins, 123, 142 Case report, 26, 30, 43, 58, 123 Caspase, 19, 40, 123 Cations, 123, 135 Cause of Death, 15, 123 Celecoxib, 72, 123 Cell Cycle, 11, 84, 88, 123, 124, 128, 144 Cell Death, 7, 15, 26, 120, 123, 128, 139 Cell Differentiation, 123, 147 Cell Division, 120, 123, 128, 138, 142 Cell membrane, 123, 127, 135 Cell motility, 9, 123 Cell proliferation, 123, 147 Cell Transplantation, 71, 123 Central Nervous System, 4, 13, 24, 28, 42, 48, 55, 62, 74, 77, 83, 122, 123, 130, 139, 143, 150 Cerebellar, 73, 123 Cerebellum, 123, 124, 143 Cerebral, 70, 72, 73, 79, 121, 122, 124, 130 Cerebral hemispheres, 121, 122, 124, 130 Cerebrum, 124 Chemopreventive, 124, 129 Chromatin, 8, 120, 124, 140 Chromosomal, 11, 29, 124 Chromosome, 31, 124 Chronic, 122, 124, 134, 139
CIS, 9, 37, 124 Cisplatin, 20, 22, 25, 43, 50, 54, 57, 83, 91, 124 Clinical Medicine, 124, 143 Clinical trial, 3, 4, 5, 6, 11, 12, 13, 14, 15, 16, 17, 18, 49, 65, 79, 82, 101, 124, 144, 145 Cloning, 121, 124 Coagulation, 122, 124, 142, 150 Collagen, 121, 124, 129, 137 Colorectal, 16, 87, 125 Colorectal Cancer, 16, 125 Combination chemotherapy, 4, 125 Combination Therapy, 83, 86, 88, 125 Complement, 125, 142, 147 Complementary and alternative medicine, 57, 64, 125 Complementary medicine, 57, 125 Complete response, 26, 125 Computational Biology, 101, 125 Computed tomography, 125, 126, 146 Computerized axial tomography, 126, 146 Concomitant, 27, 40, 126 Connective Tissue, 122, 124, 126, 130, 136, 146, 149 Consolidation, 59, 126 Contraindications, ii, 126 Contralateral, 126, 129 Conventional therapy, 18, 20, 126 Conventional treatment, 3, 126 Coronary, 126, 138 Coronary Thrombosis, 126, 138 Curative, 126, 150 Cyclophosphamide, 6, 126, 133 Cysteine, 126 Cystine, 10, 126 Cystitis, 30, 126 Cytokine, 44, 126, 129, 150 Cytomegalovirus, 126, 130 Cytomegalovirus Infections, 126, 130 Cytoplasm, 120, 123, 127, 131, 139, 140 Cytosine, 84, 127 Cytotoxic, 5, 11, 18, 28, 33, 34, 46, 49, 51, 63, 64, 85, 127, 145, 147 Cytotoxic chemotherapy, 5, 51, 64, 127 Cytotoxicity, 5, 11, 18, 26, 27, 40, 41, 124, 127 D Dacarbazine, 18, 28, 39, 41, 127 Databases, Bibliographic, 101, 127 De novo, 4, 18, 127 Deletion, 120, 127
Index 157
Depolarization, 127, 147 Diagnostic procedure, 81, 93, 127 Diaphragm, 127, 142 Diarrhea, 16, 127 Diffusion, 127, 135 Digestion, 121, 122, 127, 134, 136, 149 Digestive system, 80, 127, 139 Dihydrotestosterone, 127, 145 Direct, iii, 16, 95, 124, 127, 145 Docetaxel, 46, 55, 63, 127 Dose-limiting, 83, 86, 87, 127 Drive, ii, vi, 53, 127, 135 Drug Interactions, 96, 127 Drug Resistance, 4, 5, 11, 12, 33, 128 Drug Tolerance, 128, 150 Dura mater, 128, 137, 141 E Efficacy, 4, 6, 9, 11, 17, 18, 20, 39, 40, 42, 77, 128, 151 Electrons, 121, 128, 135, 140, 145 Embryo, 123, 128, 133 Endothelial cell, 121, 128, 150 Enhancer, 8, 128 Environmental Health, 100, 102, 128 Enzyme, 4, 5, 18, 122, 123, 128, 138, 142, 144, 145, 147, 149, 150, 151, 152, 153 Enzyme Inhibitors, 128, 142 Epigastric, 128, 141 Epithelium, 121, 128, 135 Erythrocytes, 119, 122, 128, 145, 147 Escalation, 36, 46, 128 Esophagus, 127, 128, 149 Etoposide, 36, 58, 62, 128 Exocrine, 128, 141 External-beam radiation, 129, 135, 145, 153 Extracellular, 9, 120, 126, 129, 137 Extracellular Matrix, 9, 126, 129, 137 Extracellular Matrix Proteins, 129, 137 Extracellular Space, 10, 129 Extraction, 27, 129 Extraocular, 67, 129 Eye Infections, 117, 129 F Family Planning, 101, 129 Fat, 121, 122, 129, 147, 148 Fenretinide, 9, 129 Fibrinogen, 129, 142, 150 Filgrastim, 72, 129 Fixation, 129, 147 Fold, 85, 130 Fungus, 130, 139
G Gallbladder, 117, 127, 130 Gamma Rays, 130, 145 Ganciclovir, 45, 130 Ganglia, 130, 139 Gastric, 28, 130 Gastrin, 130, 132 Gastrointestinal, 70, 120, 122, 130, 137, 149, 150 Gene, 7, 8, 9, 10, 19, 43, 45, 48, 51, 117, 121, 130 Gene Silencing, 9, 130 Gene-modified, 10, 130 Genetic testing, 9, 130 Genotype, 118, 130, 141 Gestation, 9, 130 Gland, 130, 136, 141, 144, 146, 149 Glioblastoma multiforme, 4, 23, 26, 30, 33, 39, 40, 46, 47, 65, 66, 69, 70, 72, 74, 78, 92, 131 Glucose, 6, 58, 131 Glucuronic Acid, 131, 132 Glutamate, 10, 131 Governing Board, 131, 143 Grade, 21, 25, 27, 33, 36, 38, 39, 44, 45, 47, 48, 49, 58, 59, 61, 70, 72, 73, 79, 82, 83, 122, 131 Graft, 10, 118, 131, 132, 133 Graft Rejection, 10, 131, 133 Granulocyte Colony-Stimulating Factor, 129, 131 Granulocytes, 131, 147, 153 H Hematologic malignancies, 131, 136 Hematopoietic Stem Cells, 7, 9, 10, 131 Hemoglobin, 119, 128, 131, 150 Hemolytic, 131, 150 Hemorrhage, 132, 149 Heparin, 67, 132 Hepatic, 35, 118, 132 Hereditary, 132, 146, 150 Heredity, 130, 132 Herpes, 45, 132 Herpes Zoster, 132 Histidine, 132, 134 Histology, 18, 132 Histone Deacetylase, 8, 132 Homologous, 132, 147, 149 Hormone, 23, 117, 130, 132, 147, 150 Hormone therapy, 117, 132 Host, 118, 120, 132, 133, 152 Humoral, 131, 132
158 Temozolomide
Hydrogen, 117, 121, 129, 132, 138, 140, 144 Hydrolysis, 124, 132, 135, 142, 143 Hypersensitivity, 118, 132, 147 Hypnotic, 120, 132, 150 Hypothalamic, 70, 132 Hypothalamus, 132 I Id, 56, 64, 106, 112, 114, 132 Ifosfamide, 26, 133 Imidazole, 18, 35, 133 Immune response, 117, 119, 131, 133, 147, 149, 151, 152 Immune system, 28, 65, 73, 121, 133, 136, 152, 153 Immunity, 34, 133 Immunization, 133, 147 Immunoglobulins, 133, 142 Immunologic, 133, 145 Immunology, 117, 133 Immunosuppressant, 118, 133 Immunosuppressive, 126, 133 Immunosuppressive therapy, 133 Immunotherapy, 45, 121, 133 Impairment, 129, 133, 137 Implant radiation, 133, 134, 135, 145, 153 In vitro, 5, 6, 7, 11, 20, 31, 34, 40, 41, 133 In vivo, 6, 7, 10, 12, 20, 32, 59, 132, 133 Indicative, 133, 141, 152 Induction, 6, 19, 133 Infarction, 126, 133, 138 Infection, 121, 126, 129, 133, 136, 153 Inflammation, 118, 119, 126, 129, 132, 134, 137, 141, 148 Infusion, 16, 67, 134 Initiation, 134, 151 Initiator, 19, 134 Inlay, 134, 146 Inorganic, 124, 134 Interferon, 41, 46, 67, 75, 86, 87, 134 Interferon Alfa-2b, 41, 134 Interferon-alpha, 134 Internal radiation, 134, 135, 145, 153 Interstitial, 122, 129, 134, 135, 153 Intestine, 87, 88, 122, 125, 134, 135 Intracellular, 8, 122, 133, 134, 147 Intracranial tumors, 20, 134 Intraocular, 67, 72, 74, 134 Intrathecal, 18, 51, 59, 84, 134 Intrathecal chemotherapy, 59, 84, 134 Intravenous, 16, 35, 58, 67, 86, 87, 134 Intrinsic, 4, 8, 9, 117, 121, 134 Invasive, 133, 134, 136
Ion Channels, 10, 120, 135 Ion Transport, 10, 135 Ionizing, 118, 135, 145 Ions, 10, 121, 132, 135 Irinotecan, 37, 54, 58, 60, 62, 63, 66, 70, 71, 73, 135 Iris, 67, 119, 135 Irradiation, 20, 31, 40, 44, 135, 153 J Joint, 14, 135, 149 Jurkat Cells, 25, 135 K Kb, 100, 135 Ketoconazole, 16, 135 L Large Intestine, 125, 127, 134, 135, 145, 147 Leiomyosarcoma, 68, 69, 135 Leptomeningeal metastases, 78, 135 Lesion, 18, 136 Lethal, 5, 14, 18, 136 Leukemia, 4, 6, 29, 48, 51, 54, 59, 77, 83, 131, 135, 136 Leukocytes, 122, 131, 134, 136, 138, 140, 151 Leukopenia, 83, 86, 87, 136 Library Services, 112, 136 Ligament, 136, 144 Liver, 9, 67, 87, 117, 118, 121, 126, 127, 130, 131, 132, 136, 143, 146 Liver scan, 136, 146 Localization, 8, 136 Localized, 8, 129, 133, 136, 142 Lomustine, 4, 42, 62, 69, 72, 79, 136, 140 Lymph, 87, 128, 136, 139 Lymph node, 87, 136, 139 Lymphatic, 134, 136, 148 Lymphatic system, 136, 148 Lymphocyte, 119, 136 Lymphoid, 119, 136, 143 Lymphoma, 26, 29, 38, 42, 54, 59, 69, 78, 83, 131, 136, 139 M Macrophage, 32, 136 Magnetic Resonance Imaging, 136, 146 Malignant mesothelioma, 137, 138 Malignant tumor, 11, 18, 137 Marimastat, 39, 137 Matrix metalloproteinase, 39, 137 Maximum Tolerated Dose, 17, 128, 137 Mechlorethamine, 137, 143 Medical Oncology, 33, 38, 42, 43, 44, 63, 137, 145
Index 159
MEDLINE, 101, 137 Medulloblastoma, 51, 58, 83, 137 Megakaryocytes, 122, 137 Melanin, 135, 137 Melanocytes, 137 Membrane, 120, 123, 125, 127, 135, 137, 142, 143, 147, 151 Meninges, 123, 128, 137 Meningioma, 68, 137 Meningitis, 19, 83, 137 Mental Disorders, 80, 137 Mesothelioma, 22, 137, 138 Metastasis, 76, 137, 138 Metastasize, 18, 138, 146 Metastatic cancer, 87, 138 Methyltransferase, 4, 9, 10, 25, 27, 34, 41, 43, 54, 58, 138 MI, 115, 138 Microbe, 138, 151 Microorganism, 138, 152 Microtubules, 138, 141 Mitosis, 120, 138 Mitotic, 127, 128, 138, 152 Mitotic inhibitors, 127, 138 Modification, 10, 138, 144 Modulator, 6, 138 Molecular, 7, 8, 12, 20, 31, 54, 60, 61, 101, 103, 121, 125, 129, 132, 138, 151 Molecule, 16, 119, 121, 125, 132, 138, 140, 145, 147, 151, 152 Monitor, 8, 15, 138, 140 Monoclonal, 135, 138, 145, 153 Monocytes, 136, 138, 150 Mononuclear, 31, 138, 139, 151 Morphine, 122, 139 Motility, 139 Mucositis, 139, 150 Mutagenic, 6, 118, 139 Mutagenicity, 6, 8, 139 Mycosis, 69, 70, 82, 85, 139 Mycosis Fungoides, 69, 70, 82, 85, 139 Myelin, 139, 140 Myelosuppression, 6, 21, 83, 86, 87, 139 Myelotoxic, 6, 139 Myocardium, 138, 139 N NCI, 1, 11, 14, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 99, 124, 139 Necrosis, 120, 130, 133, 138, 139 Need, 19, 83, 84, 86, 87, 107, 137, 139, 150 Neoplasia, 139 Neoplasm, 18, 67, 76, 139, 146, 152
Neoplastic, 18, 46, 51, 83, 85, 136, 139 Neoplastic meningitis, 18, 46, 51, 83, 139 Nerve, 74, 139, 140, 141, 143, 149, 151 Nervous System, 4, 18, 123, 139, 149 Neuroblastoma, 16, 139 Neurologic, 77, 130, 139 Neurotoxic, 10, 139 Neutrons, 118, 135, 140, 145 Neutrophils, 129, 131, 136, 140 Nitrogen, 118, 126, 129, 130, 140 Nitrosoureas, 4, 140 Nonmalignant, 10, 140 Non-small cell lung cancer, 47, 73, 140 Nuclear, 8, 120, 122, 128, 130, 139, 140 Nucleic acid, 127, 140, 144 Nucleus, 8, 120, 124, 127, 130, 138, 139, 140, 144, 149 O Ocular, 8, 140 Oligodendroglial, 38, 59, 140 Oligodendroglial tumors, 38, 59, 140 Oligodendroglioma, 31, 42, 44, 58, 61, 62, 65, 66, 70, 71, 72, 73, 74, 75, 92, 140 Oncologist, 48, 51, 64, 140 Ophthalmic, 8, 140 Overexpress, 12, 140 Ovum, 130, 140 Oxidation, 117, 126, 140 P Pachymeningitis, 137, 141 Paclitaxel, 58, 141 Paediatric, 36, 141 Palliative, 141, 150 Pancreas, 87, 88, 117, 127, 141 Pancreatic, 22, 141 Pancreatic cancer, 22, 141 Parietal, 141, 142 Particle, 141, 151 Pathologic, 120, 121, 126, 132, 141 Pathologic Processes, 120, 141 Pelvic, 141, 144 Peptide, 141, 143, 144 Performance status, 38, 141 Peripheral blood, 31, 73, 134, 141 Peripheral stem cell transplantation, 71, 141 Pharmacodynamic, 5, 16, 17, 35, 55, 141 Pharmacokinetic, 5, 14, 17, 22, 35, 36, 62, 141 Pharmacologic, 9, 14, 141, 151 Phenotype, 25, 54, 58, 141 Phenylbutyrate, 12, 141
160 Temozolomide
Phospholipases, 142, 147 Photodynamic therapy, 6, 142 Photosensitizer, 6, 142 Physiologic, 12, 118, 142, 145 Pigment, 137, 142 Pilot study, 59, 142 Plants, 118, 131, 142, 151 Plasma, 17, 27, 30, 118, 119, 123, 129, 131, 142, 147 Plasma cells, 119, 142 Plasma protein, 17, 118, 142 Platelet Activation, 142, 147 Platelets, 137, 139, 142 Platinum, 124, 142 Pleura, 142 Pleural, 22, 142 Podophyllotoxin, 128, 142 Polymerase, 6, 26, 29, 31, 39, 40, 42, 51, 142 Polypeptide, 118, 124, 129, 143, 150, 153 Polyposis, 125, 143 Polysaccharide, 119, 143 Pons, 122, 143 Posterior, 124, 135, 141, 143 Postnatal, 9, 143, 148 Postsynaptic, 143, 147 Potentiate, 5, 143 Potentiation, 11, 27, 40, 41, 84, 85, 143, 147 Practicability, 143, 151 Practice Guidelines, 102, 143 Preclinical, 6, 10, 12, 18, 40, 143 Precursor, 29, 54, 59, 126, 131, 143 Prednisone, 143 Primary central nervous system lymphoma, 59, 63, 143 Primary tumor, 6, 143 Primitive neuroectodermal tumors, 137, 143 Procarbazine, 4, 23, 30, 42, 47, 59, 62, 69, 143 Progression, 18, 84, 88, 92, 119, 143, 151 Progressive, 23, 33, 37, 39, 48, 66, 70, 74, 75, 78, 123, 128, 131, 139, 142, 143, 152 Promoter, 8, 19, 144 Prospective study, 57, 144 Prostate, 13, 19, 23, 87, 88, 129, 144 Protease, 125, 144 Protein C, 67, 118, 120, 144 Protein S, 121, 144 Proteins, 6, 11, 118, 119, 123, 124, 125, 129, 137, 138, 140, 141, 142, 144, 151 Protocol, 12, 13, 75, 76, 143, 144 Protons, 118, 132, 135, 144, 145
Proto-Oncogene Proteins, 141, 144 Proto-Oncogene Proteins c-mos, 141, 144 Public Policy, 101, 144 Publishing, 21, 144 Pulse, 138, 144 Purines, 5, 144 Q Quality of Life, 30, 67, 144 R Radiation oncologist, 13, 14, 140, 145 Radiation Oncology, 13, 43, 145 Radiation therapy, 17, 23, 71, 72, 73, 74, 76, 77, 79, 84, 87, 88, 91, 117, 129, 134, 135, 145, 153 Radioactive, 122, 132, 133, 134, 135, 136, 140, 145, 146, 153 Radioimmunotherapy, 145 Radiolabeled, 135, 145, 153 Radiology, 12, 15, 145 Radiotherapy, 3, 13, 14, 27, 37, 42, 59, 84, 122, 135, 145, 153 Randomized, 37, 41, 69, 73, 76, 128, 145 Receptor, 7, 16, 119, 145, 147 Recombinant, 86, 87, 134, 145, 152 Rectal, 82, 145 Rectum, 120, 122, 125, 127, 135, 144, 145 Recurrence, 60, 145 Red blood cells, 128, 131, 139, 145 Reductase, 26, 145 Refer, 1, 125, 129, 132, 136, 140, 145 Refraction, 145, 148 Refractory, 15, 18, 23, 35, 36, 63, 68, 92, 145 Regimen, 44, 69, 128, 146 Relapse, 10, 15, 23, 28, 32, 33, 47, 51, 146 Remission, 145, 146 Renal cell cancer, 23, 146 Respiration, 138, 146 Restoration, 10, 146, 153 Retinoblastoma, 8, 146 Retinoids, 9, 117, 146 Ribose, 6, 26, 29, 31, 39, 42, 51, 117, 146 Risk factor, 144, 146 S Salivary, 126, 127, 141, 146 Salivary glands, 126, 127, 146 Sarcoma, 16, 18, 46, 67, 68, 84, 106, 143, 146, 148 Scans, 67, 146 Screening, 13, 124, 146 Secondary tumor, 138, 146 Secretion, 10, 146, 147 Seizures, 130, 146
Index 161
Semen, 144, 147 Semisynthetic, 123, 128, 147 Senescence, 48, 147 Sensitization, 43, 85, 147 Sequencing, 9, 147 Side effect, 6, 73, 83, 86, 87, 95, 117, 121, 126, 127, 139, 147, 151 Signal Transduction, 7, 16, 147 Signs and Symptoms, 146, 147 Silicon, 6, 147 Silicon Dioxide, 147 Skeleton, 135, 147 Small cell lung cancer, 78, 147 Small intestine, 132, 134, 147 Social Environment, 144, 147 Soft tissue, 23, 46, 68, 121, 147, 148 Soft tissue sarcoma, 23, 46, 68, 148 Solid tumor, 7, 12, 15, 25, 36, 37, 62, 71, 75, 76, 77, 78, 119, 136, 148 Somatic, 132, 138, 148, 149 Specialist, 107, 148 Species, 85, 118, 123, 138, 148, 149, 151, 152, 153 Spectrometer, 15, 148 Spectrum, 8, 83, 135, 148 Sperm, 124, 148 Spinal cord, 68, 120, 122, 123, 128, 134, 136, 137, 139, 141, 143, 148 Sporadic, 146, 148 Squamous, 140, 148 Squamous cell carcinoma, 140, 148 Staging, 146, 148 Steady state, 17, 148 Stem cell transplantation, 71, 148 Stem Cells, 7, 10, 141, 148 Sterility, 126, 148 Steroids, 17, 77, 148 Stimulus, 127, 135, 149 Stomach, 117, 127, 128, 130, 132, 147, 149 Strand, 32, 84, 88, 142, 149 Stroke, 80, 100, 149 Stroma, 135, 149 Stromal, 70, 122, 149 Stromal Cells, 122, 149 Stromal tumors, 70, 149 Subarachnoid, 18, 83, 149 Subcutaneous, 15, 20, 87, 149 Subspecies, 148, 149 Substance P, 146, 149 Substrate, 5, 16, 128, 149 Suppression, 130, 149 Supratentorial, 23, 36, 149
Survival Rate, 4, 149 Symphysis, 144, 149 Synaptic, 147, 149 Synthetic retinoid, 129, 149 Systemic, 16, 18, 44, 63, 83, 96, 121, 134, 135, 145, 149, 153 T Telomerase, 19, 31, 149 Teratogenic, 118, 150 Testicular, 29, 82, 150 Testis, 150 Testosterone, 145, 150 Thalassemia, 9, 150 Thalidomide, 33, 38, 41, 48, 51, 68, 72, 74, 76, 77, 87, 88, 92, 150 Theophylline, 144, 150 Therapeutics, 5, 25, 34, 42, 50, 61, 96, 150 Thiotepa, 84, 150 Thrombin, 129, 144, 150 Thrombomodulin, 144, 150 Thrombosis, 144, 149, 150 Thymidine, 45, 150 Thymidine Kinase, 45, 150 Tolerance, 21, 50, 117, 122, 150 Tomography, 32, 59, 126, 150 Topoisomerase inhibitors, 135, 150 Topotecan, 16, 40, 151 Toxic, iv, 5, 6, 9, 10, 32, 85, 88, 118, 127, 133, 142, 150, 151 Toxicity, 4, 6, 9, 15, 16, 17, 18, 24, 27, 54, 83, 85, 86, 87, 127, 137, 151 Toxicology, 102, 151 Toxins, 119, 131, 133, 145, 151 Trace element, 147, 151 Transcriptase, 149, 151 Transcription Factors, 8, 151 Transduction, 9, 26, 147, 151 Transfection, 121, 151 Translating, 16, 151 Translational, 5, 15, 130, 151 Transmitter, 120, 135, 151 Transplantation, 10, 106, 133, 141, 151 Treatment Outcome, 12, 151 Tumor model, 20, 151 Tumor Necrosis Factor, 150, 151 Tumor-derived, 42, 55, 62, 151 Tumour, 27, 29, 34, 59, 85, 120, 152 U Unconscious, 132, 152 Unresectable, 23, 48, 68, 69, 70, 72, 77, 152 Urethra, 144, 152 Urinary, 26, 126, 152
162 Temozolomide
Urine, 27, 121, 146, 152 Uterus, 135, 152 V Vaccine, 117, 144, 151, 152 Vascular, 12, 133, 134, 152 Vector, 7, 10, 19, 151, 152 Vein, 67, 134, 140, 152 Vertebrae, 148, 152 Veterinary Medicine, 101, 152 Vinblastine, 22, 54, 57, 152 Vinca Alkaloids, 152 Vincristine, 42, 59, 62, 69, 143, 152 Vinorelbine, 69, 152 Viral, 9, 151, 152 Virulence, 151, 152 Virus, 45, 120, 128, 134, 151, 152 Viscera, 139, 148, 152
Visceral, 6, 152 Vitro, 7, 132, 152 Vivo, 6, 7, 10, 20, 153 W White blood cell, 119, 129, 136, 139, 142, 153 Wound Healing, 137, 153 X Xenograft, 11, 16, 25, 28, 34, 42, 54, 55, 58, 62, 63, 119, 151, 153 X-ray, 43, 71, 73, 74, 76, 77, 79, 126, 130, 135, 140, 145, 146, 153 X-ray therapy, 135, 153 Y Yeasts, 130, 141, 153 Z Zymogen, 144, 153
Index 163
164 Temozolomide
