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Drug Resistance As a Biochemical Target in Cancer Chemotherapy
- 1st Edition - November 12, 1991
- Editor: Makoto Ogawa
- Language: English
- Paperback ISBN:9 7 8 - 0 - 1 2 - 4 3 1 5 8 6 - 0
- eBook ISBN:9 7 8 - 0 - 3 2 3 - 1 5 3 8 8 - 1
Drug Resistance as a Biochemical Target in Cancer Chemotherapy covers the proceedings of the 13th Bristol-Myers Squibb Symposium on Cancer Research, entitled ""Drug Resistance as a… Read more
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Request a sales quoteDrug Resistance as a Biochemical Target in Cancer Chemotherapy covers the proceedings of the 13th Bristol-Myers Squibb Symposium on Cancer Research, entitled ""Drug Resistance as a Biochemical Target in Cancer Chemotherapy"", hosted by the Japanese Foundation for Cancer Research in Tokyo. This book is divided into four parts encompassing 18 chapters that summarize the results of both preclinical and clinical research on circumvention of drug resistance. The first two parts discuss the genetic aspects of multidrug resistance and the proteins involved in drug resistance. These parts also examine the structure, function, and expression of P-glycoproteins, with an emphasis on the role of these proteins as targets for cancer chemotherapy. The third part describes the methods for detection of P-glycoprotein and its antagonists to counter clinical drug resistance. This topic is followed by a discussion on the interactions among steroid hormones, steroid hormone receptors, antiandrogens, biological-response modifiers, and cytotoxic drugs in human breast cancer. The concluding part explores the clinical applications of chemosensitizers in cancer therapy. This part also considers the alternative clinical approaches against drug failure, including non-crosss-resistant therapies, autologous bone marrow transplantation, dose-intensive therapy, and high-dose chemotherapy. Biomedical scientists and researchers and clinicians will find this book invaluable.
Contributors
Editor's Foreword
Foreword
Preface
Introduction to the Bristol-Myers Squibb Drug Resistance in Cancer Symposium
Text
References
Part I Genetic Aspects of Multidrug Resistance
1 The P-glycoprotein Gene Family
I. Introduction
II. P-glycoprotein Genes in Unicellular Eukaryotes
III. P-glycoprotein Genes in Simple Multicellular Eukaryotes
IV. The P-glycoprotein Genes of Mammals
V. The Human MDR3/2 Gene
VI. Outlook
References
2 Molecular Genetic Analysis of P-glycoprotein Function and Expression in Human Cells
I. Introduction
II. Human MDR Genes: Structure and Expression
III. The Role of the MDR1 Gene in Multidrug Resistance
IV. Structural and Mutational Analysis of P-glycoprotein Function
V. Diagnostics of MDR1 Expression in Human Cancer by Polymerase Chain Reaction
References
3 Function of the Multidrug Transporter
I. Introduction
II. The Localization of P-glycoprotein in Normal Tissues Suggests a Role in Transepithelial Transport
III. Model Systems In Which P-glycoprotein Acts as an Energy-dependent Drug Transporter
IV. Multidrug Transport May Involve Extraction of Hydrophobie Drugs from Lipid Bilayers
V. Transgenic Mice Expressing the MDR1 Gene in Bone Marrow
VI. Conclusions
References
4 A Comparison of the Structure, Function, and Expression of P-glycoproteins Encoded by mdrla in mdr1b in Mouse
I. Introduction
II. Structural Differences between P-glycoprotein Family Members
III. Functional Differences Associated with mdr1a and mdr1b
IV. Differences in Expression between mdr1a and mdr1b
V. Conclusions
References
Part II Proteins Involved in Drug Resistance as Targets for Cancer Chemotherapy
5 Multidrug Resistance: Basic Approaches for Reversal
I. Introduction
II. Basic Properties of the P-glycoprotein of MDR Cells
III. P-glycoprotein as a Target of Cancer Chemotherapy
IV. Application of Monoclonal Antibodies for Therapy of Human Resistant Cells
V. Search for New Agents to Reverse Drug Resistance
VI. Development and Evaluation of New Antitumor Agents Effective against Human Drug-resistant Tumors
VII. Conclusion
References
6 Expression of P-glycoprotein Isoforms
I. Introduction
II. P-glycoprotein Gene Family Members in Different Species
III. Localization of P-glycoprotein Isoforms in Chinese Hamster
IV. Concluding Remarks
References
7 The Use of Yeast and Yeast Strains Expressing Human DNA Topoisomerases in the Study of Anticancer Drugs
I. Introduction
II. DNA Topoisomerases as Targets of Therapeutics
III. Yeast as a Genetic System for the Study of DNA Topoisomerase-targeting Anticancer Drugs
IV. Expression of Human DNA Topoisomerases I and II in Yeast for Drug Screening or for the Construction of Drug-resistant Mutant Human Enzymes
V. A Unique Feature of Topoisomerasetargeting Drugs That Interfere with Transesterification
VI. Potential Targets for the Development of New Therapeutics
VII. Drugs of the Same Theme but Different Colors
VIII. Concluding Remarks
References
8 Mechanisms of Tumor Cell Killing by Topoisomerase Poisons
I. Introduction
II. Topoisomerase I Poisons
III. Topoisomerase II Poisons
References
9 Regulation of Glutathione Transferase P Gene: Implications in Carcinogenesis and Drug Resistance
I. Introduction
II. Results and Discussion
III. Concluding Remarks
References
Part III Approaches Against Clinical Drug Resistance
10 Clinical Detection and Role of Differentiation in Multidrug Resistance
I. Introduction
II. Methods of P-glycoprotein Detection
III. Role of Differentiation in Multidrug Resistance
IV. Use of P-glycoprotein Antagonists
References
11 Detection of Multidrug-Resistant Human Cancer Cells by Monoclonal Antibodies
I. Introduction
II. Sensitivity and Specificity of Monoclonal Antibodies, MRK16-F(ab')2 and MRK20-F(ab')2
III. Reactivity of Monoclonal Antibodies with Normal Leukocytes in Peripheral Blood
IV. Reactivity of MRK16-F(ab')2 and MRK20-F(ab')2 with Clinical Samples
V. Summary
References
12 Molecular Analysis of Human IL-2 and IL-2 Receptors
I. Introduction
II. Structure of Human IL-2
III. Structure of the IL-2 Receptor Complex
IV. IL-2Rß Chain and Signal Transduction
V. IL-2Rß Is Functional in a Neural Cell Line
VI. Summary
References
13 The Interactions among Steroid Hormones, Steroid Hormone Receptors, Antiestrogens, Biological-response Modifiers and Cytotoxic Drugs in Human Breast Cancer
I. Introduction
II. Effects of Biological-response Modifiers and Cytotoxic Drugs on Steroid Hormone—Receptor Expression and Response to Antiestrogens
III. Effects of Hormonal Therapies on Response to Cytotoxic Drugs
IV. Effects of Cytotoxic Drugs on Serum Hormones
V. Conclusions
References
Part IV Clinical Approaches Against Drug Failure
14 Clinical Detection of Multidrug Resistance and Reversal with Chemosensitizing Agents
I. Introduction
II. Clinical Applications of Chemosensitizers in Cancer Therapy
III. Further Studies of Chemosensitizers
References
15 Clinical Evaluation of Non-cross-resistant Therapies in Advanced Hodgkin's Disease
I. Introduction
II. Rise of ABVD and Non-cross-resistant Regimens
III. Attempts to Overcome Drug Resistance by Alternating MOPP and ABVD
IV. More Recent Findings with Non-crossresistant Regimens
V. Attempts to Overcome Drug Resistance by High-dose Therapy
VI. Comment
References
16 Autologous Bone Marrow Transplantation for Hematologic Malignancy
I. Overview
II. Rationale
III. Critical Issues
IV. Clinical Studies
V. Future Directions
VI. Conclusion
References
17 Dose-intensive Therapy: A Strategy to Avoid Drug Resistance in Solid Tumors
I. Considerations in the Design of a Highdose Regimen for Solid Tumors
II. Breast Cancer
III. Bone Marrow Transplantation in Breast Cancer
IV. Bone Marrow Involvement
V. Supportive Care
VI. Summary of ABMT in Breast Cancer
References
18 High-dose Chemotherapy with Autologous Bone Marrow Transplantation in Malignant Lymphomas and Breast Cancer
I. Background
II. Materials and Methods
III. Results
IV. Discussion
References
Index
- No. of pages: 368
- Language: English
- Edition: 1
- Published: November 12, 1991
- Imprint: Academic Press
- Paperback ISBN: 9780124315860
- eBook ISBN: 9780323153881