Drug Resistance As a Biochemical Target in Cancer Chemotherapy

¿Contributors Editor's Foreword Foreword Preface Introduction to the Bristol-Myers Squibb Drug Resistance in Cancer Symposium Text ReferencesPart 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.