Drug Resistance in Leukemia and Lymphoma III

ISBN-13: 9780306460555 / Angielski / Twarda / 1999 / 638 str.

G. J. Kaspers; R. Pieters; A. J. P. Veerman

Opis

Cellular drug resistance is a major limitation to the success of chemotherapy of leu- kemia and lymphoma. The importance of this has now been recognized by both clinicians and scientists. It is of utmost importance to bridge the gap between laboratory and clinic in this field of research. This is the main purpose of the series of International Symposia on Drug Resistance in Leukemia and Lymphoma. These are held every three years in Am- sterdam, The Netherlands, since 1992. This book contains the proceedings of the third of these meetings, organised in 1998. The book covers all important aspects of drug resistance in leukemia and lymphoma, both in the form of extensive reviews as in manuscripts describing original data. General mechanisms of resistance are discussed, including the drug resistance related proteins p- glycoprotein, MRP (multi-drug resistance protein) and LRP (lung resistance protein), and the role of glutathione and glutathione-S-transferases. Moreover, more drug type-specific mechanisms of resistance are a topic, such as for glucocorticoids and antifolates. Much in- formation is provided on apoptosis and its regulators, and on the results of cell culture drug resistance assays. Several papers focus on the modulation or circumvention of drug resistance.

Spis treści

Section I. Drug Resistance Related Proteins and Glutathione.- 1. MDR1/P-gp Expression as a Prognostic Factor in Acute Leukemias.- 2. Clinical Significance of P-Glycoprotein (P-gp) Expression in Childhood Acute Lymphoblastic Leukemia: Results of a 6-Year Prospective Study.- 3. Prognostic Value of P-gp Expression and Related Function in Childhood Acute Leukemia.- 4. Comparison of P-Glycoprotein Expression and Function with in Vitro Sensitivity to Anthracyclines in AML.- 5. Quinine Improves Results of Intensive Chemotherapy (IC) in Myelodysplastic Syndromes (MDS) Expressing P-Glycoprotein (PGP): Updated Results of a Randomized Study.- 6. Treatment of Poor Prognosis AML Patients Using PSC833 (Valspodar) plus Mitoxantrone, Etoposide, and Cytarabine (PSC-MEC).- 7. Assessment of P-Glycoprotein Expression by Immunocytochemistry and Flow Cytometry Using Two Different Monoclonal Antibodies Coupled with Functional Efflux Analysis in 34 Patients with Acute Myeloid Leukemia.- 8. Preliminary Immunocytochemical Studies of MDR-1 and MDR-3 Pgp Expression in B-Cell Leukaemias.- 9. A Mutation in the Promoter of the Multidrug Resistance Gene (MDR 1) in Human Hematological Malignancies May Contribute to the Pathogenesis of Resistant Disease.- 10. Reproducible Flow Cytometric Methodology for Measuring Multidrug Resistance in Leukaemic Blasts.- 11. Natural Fluorescence Imaging of Leukemic Cells for Studying Uptake and Retention of Anthracyclines.- 12. Artificial Neural Networks as Versatile Tools for Prediction of MDR-Modulatory Activity.- 13. Discordance of P-Glycoprotein Expression and Function in Acute Leukemia.- 14. Multidrug Resistance Related Proteins in Primary Cutaneous Lymphomas.- 15. The Lung Resistance Protein (LRP) Predicts Poor Outcome in Acute Myeloid Leukemia.- 16. MRP Expression in Acute Myeloid Leukemia: An Update.- 17. Evidence for Functional Discrimination between Leukemic Cells Overexpressing Multidrug-Resistance Associated Protein and P-Glycoprotein.- 18. Both Pgp and MRP1 Activities Using Calcein-AM Contribute to Drug Resistance in AML.- 19. Absolute Levels of MDR-1, MRP, and BCL-2 mRNA and Tumor Remission in Acute Leukemia.- 20. Multidrug Resistance Protein MRP1, Glutathione, and Related Enzymes: Their Importance in Acute Myeloid Leukemia.- 21. Glutathione and the Regulation of Cell Death.- 22. Evidence for the Involvement of the Glutathione Pathway in Drug Resistance in AML.- 23. Glutathione in Childhood Acute Leukaemias.- Section II. Apoptosis and Cell Death Regulations.- 24. Apoptosis: Molecules and Mechanisms.- 25. Activation of Apoptosis Pathways by Anticancer Drugs.- 26. BCL-2 Stimulates Apoptin®-Induced Apoptosis.- 27. CD95 (Fas/Apo-1) Antigen Is a New Prognostic Marker of Blast Cells of Acute Lymphoblastic Leukaemia Patients.- 28. Inhibition of Fas/Fas-Ligand Does Not Block Chemotherapy-Induced Apoptosis in Drug Sensitive and Resistant Cells.- 29. Effects of PARP Inhibition on Drug and FAS-Induced Apoptosis in Leukaemic Cells.- 30. Apoptotic Fraction in Childhood ALL Assessed by DNA in Situ Labelling Is Ploidy Independent.- 31. PCNA Bearing Structures Are Retained in Apoptotic Phase of Childhood ALL Cell Cycle.- 32. Apoptosis Corrected Proliferation Fraction in Childhood ALL Is Related to Karyotype.- 33. Proliferation and Apoptosis Does Not Affect Presenting White Cell Count in Childhood ALL.- 34. Apoptosis by Anthracyclines at Therapeutic Concentrations in MDR1+ Human Leukemic Cells.- 35. BCL-2 Expression in Childhood Leukemia versus Spontaneous Apoptosis, Drug Induced Apoptosis and in Vitro Drug Resistance.- 36. Comparison of BCL-2 and Bax Protein Expression with in Vitro Sensitivity to Ara-C and 6TG in AML.- 37. Synthetic Cyclin Dependent Kinase Inhibitors: New Generation of Potent Anti-Cancer Drugs.- 38. Factors Contributing to the Resistance to Apoptosis Induced by Topoisomerase I Inhibitors in Vincristine Resistant Cells.- 39. Two Distinct Modes of Oncoprotein Expression during Apoptosis Resistance in Vincristine and Daunorubicin Multidrug-Resistant HL60 Cells.- Section III. Risk Factors and Cell Culture Assays.- Genetic Abnormalities and Drug Resistance in Acute Lymphoblastic Leukemia>.- 41. Resistance Testing and Mechanisms of Resistance in Childhood Leukemia: Studies from Amsterdam.- 42. Pharmacokinetics of Anticancer Drugs in Vitro.- 43. Down Syndrome and Acute Myeloid Leukemia: Lessons Learned from Experience with High-Dose Ara-C Containing Regimens.- 44. Cellular Drug Resistance in Childhood Acute Myeloid Leukemia: A Mini-Review with Emphasis on Cell Culture Assays.- 45. Is in Vitro Sensitivity of Blast Cells Correlated to Therapeutic Effect in Childhood Acute Lymphoblastic Leukemia?.- 46. In Vitro Cytotoxic Drug Activity and in Vivo Pharmacokinetics in Childhood Acute Myeloid Leukemia.- 47. Prognosis in Adult AML Is Precisely Predicted by the Disc-Assay Using the Chemosensitivity-Index C1.- 48. Drug Resistance Testing of Acute Myeloid Leukemia in Adults Using the MTT Assay.- 49. MTT Assay for Drug Resistance in Childhood Acute Leukemia and Effect of Cyclosporin and Interferon: A Preliminary Report.- 50. Differential Antileukemic Activity of Prednisolone and Dexamethasone in Freshly Isolated Leukemic Cells.- 51. Activity of Vinorelbine on B-Chronic Lymphocytic Leukemia Cells in Vitro.- 52. Studies of Some Mechanisms of Drug Resistance in Chronic Myeloid Leukemia (CML).- 53. Clinical Sensitivity to Anthracyclines in Ph/BCR+ Acute Lymphoblastic Leukemia.- 54. Differential Kinetics of Drug Resistance in Human Leukaemic Cells Measured by SCGE/CLSM.- 55. Demonstration of Differences in Drug Resistance by Direct Testing of DNA Excision Repair Activity following Standard and Liposomal Daunorubicin Exposure in Normal Paediatric Marrow Using High Resolution CLSM.- 56. Microsatellite Instability Assessment in Prediction of Drug Resistance in Childhood Burkitt’s and Large Cell Diffuse Malignant Non-Hodgkin Lymphoma (MNHL).- 57. High Resolution Confocal Laser Scanning Microscopy Analysis of DNA Excision Repair Capability in Small Volume Marrow Samples Exposed to DNA Directed Treatment Moieties.- Section IV. Antifolates.- 58. Defining the Optimal Dosage of Methotrexate for Childhood Acute Lymphoblastic Leukemia: New Insights from the Lab and Clinic.- 59. Mechanisms of Methotrexate Resistance in Acute Leukemia: Decreased Transport and Polyglutamylation.- 60. Lack of Cross-Resistance between Prednisolone and Methotrexate in Childhood Acute Lymphoblastic Leukemia? A Preliminary Analysis.- Section V. Nucleoside Analogues and Growth Factors.- 61. New Developments in the Treatment of Acute Myeloid Leukemia.- 62. Aphidicolin Markedly Increases the in Vitro Sensitivity to Ara-C of Blast Cells from Patients with AML.- 63. Common Resistance Mechanisms to Nucleoside Analogues in Variants of the Human Erythroleukemic Line K562.- 64. Expression of DNA Mismatch Repair Proteins in Acute Lymphoblastic Leukaemia and Normal Bone Marrow.- 65. Effects of CSFS and Their Combinations with Chemotherapeutic Agents (Ch) on Leukemic Blasts (LB) in Children (MTT-Assay).- Section VI. Glucocorticoids.- 66. Glucocorticosteroid Therapy in Childhood Acute Lymphoblastic Leukemia.- 67. Glucocorticoid Induced Apoptosis in Leukemia.- 68. Glucocorticoid Resistance and the AP-1 Transcription Factor in Leukemia.- Section VII. Asparaginase.- 69. The Three Asparaginases: Comparative Pharmacology and Optimal Use in Childhood Leukemia.