Drug Resistance in Leukemia and Lymphoma III / Edition 1

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This volume covers all important aspects of drug resistance in leukemi a and lymphoma. General mechanisms of resistance are discussed, includ ing the drug resistance related proteins, MRP (multi drug resistance p rotein) and LRP (lung resistance protein), and the role of glutathione and glutathione-S-transferases, as well as drug-specific mechanisms o f resistance, apoptosis and its regulators and modulation of drug resi stance.

Incl. proteins, glutathione, mecha- nisms of resistance, apoptosis; modulation & circumvention.

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Editorial Reviews

Documents the 1998 meeting of an international symposium held every three years in Amsterdam to share recent research into cellular drug resistance to chemotherapy for the two types of cancer<-->a major limitation on the approach's success. The 69 contributions cover drug resistance and related proteins and glutathione, apoptosis and cell death regulation, risk factors and cell culture assays, antifolates, nucleoside analogues and growth factors, glucocorticoids, and asparaginase. Among specific topics are proteins related to multi-drug resistance in primary cutaneous lymphomas, activating apoptosis pathways by anti-cancer drugs, in-vitro cytotoxic drug activity and in-vivo pharmacokinetics in childhood acute myeloid leukemia, the expression of DNA mismatched repair proteins in acute lymphoblastic leukemia and normal bone marrow, and glucocorticoid-induced apoptosis. Annotation c. Book News, Inc., Portland, OR (booknews.com)
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Product Details

Table of Contents

1 MDR 1/P-gp Expression as a Prognostic Factor in Acute Leukemias 1
2 Clinical Significance of P-Glycoprotein (P-gp) Expression in Childhood Acute Lymphoblastic Leukemia: Results of a 6-Year Prospective Study 11
3 Prognostic Value of P-gp Expression and Related Function in Childhood Acute Leukemia 21
4 Comparison of P-Glycoprotein Expression and Function with in Vitro Sensitivity to Anthracyclines in AML 29
5 Quinine Improves Results of Intensive Chemotherapy (IC) in Myelodysplastic Syndromes (MDS) Expressing P-Glycoprotein (PGP): Updated Results of a Randomized Study 35
6 Treatment of Poor Prognosis AML Patients Using PSC833 (Valspodar) plus Mitoxantrone, Etoposide, and Cytarabine (PSC-MEC) 47
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 57
8 Preliminary Immunocytochemical Studies of MDR-1 and MDR-3 Pgp Expression in B-Cell Leukemias 65
9 A Mutation in the Promoter of the Multidrug Resistance Gene (MDR1) in Human Hematological Malignancies May Contribute to the Pathogenesis of Resistant Disease 71
10 Reproducible Flow Cytometric Methodology for Measuring Multidrug Resistance in Leukaemic Blasts 77
11 Natural Fluorescence Imaging of Leukemic Cells for Studying Uptake and Retention of Anthracyclines 89
12 Artificial Neural Networks as Versatile Tools for Prediction of MDR-Modulatory Activity 95
13 Discordance of P-Glycoprotein Expression and Function in Acute Leukemia 107
14 Multidrug Resistance Related Proteins in Primary Cutaneous Lymphomas 119
15 The Lung Resistance Protein (LRP) Predicts Poor Outcome in Acute Myeloid Leukemia 133
16 MRP Expression in Acute Myeloid Leukemia: An Update 141
17 Evidence for Functional Discrimination between Leukemic Cells Overexpressing Multidrug-Resistance Associated Protein and P-Glycoprotein 151
18 Both Pgp and MRP1 Activities Using Calcein-AM Contribute to Drug Resistance in AML 161
19 Absolute Levels of MDR-1, MRP, and BCL-2 mRNA and Tumor Remission in Acute Leukemia 177
20 Multidrug Resistance Protein MRP1, Glutathione, and Related Enzymes: Their Importance in Acute Myeloid Leukemia 187
21 Glutathione and the Regulation of Cell Death 199
22 Evidence for the Involvement of the Glutathione Pathway in Drug Resistance in AML 205
23 Glutathione in Childhood Acute Leukemias 211
24 Apoptosis: Molecules and Mechanisms 217
25 Activation of Apoptosis Pathways by Anticancer Drugs 237
26 BCL-2 Stimulates Apoptin-Induced Apoptosis 245
27 CD95 (Fas/Apo-1) Antigen Is a New Prognostic Marker of Blast Cells of Acute Lymphoblastic Leukemia Patients 251
28 Inhibition of Fas/Fas-Ligand Does Not Block Chemotherapy-Induced Apoptosis in Drug Sensitive and Resistant Cells 259
29 Effects of PARP Inhibition on Drug and FAS-Induced Apoptosis in Leukaemic Cells 267
30 Apoptotic Fraction in Childhood ALL Assessed by DNA in Situ Labelling Is Ploidy Independent 281
31 PCNA Bearing Structures Are Retained in Apoptotic Phase of Childhood ALL Cell Cycle 289
32 Apoptosis Corrected Proliferation Fraction in Childhood ALL Is Related to Karyotype 297
33 Proliferation and Apoptosis Does Not Affect Presenting White Cell Count in Childhood ALL 305
34 Apoptosis by Anthracyclines at Therapeutic Concentrations in MDR1+ Human Leukemic Cells 313
35 BCL-2 Expression in Childhood Leukemia versus Spontaneous Apoptosis, Drug Induced Apoptosis and in Vitro Drug Resistance 325
36 Comparison of BCL-2 and Bax Protein Expression with in Vitro Sensitivity to Ara-C and 6TG in AML 335
37 Synthetic Cyclin Dependent Kinase Inhibitors: New Generation of Potent Anti-Cancer Drugs 341
38 Factors Contributing to the Resistance to Apoptosis Induced by Topoisomerase I Inhibitors in Vincristine Resistant Cells 355
39 Two Distinct Modes of Oncoprotein Expression during Apoptosis Resistance in Vincristine and Daunorubicin Multidrug-Resistant HL60 Cells 365
40 Genetic Abnormalities and Drug Resistance in Acute Lymphoblastic Leukemia 383
41 Resistance Testing and Mechanisms of Resistance in Childhood Leukemia: Studies from Amsterdam 391
42 Pharmacokinetics of Anticancer Drugs in Vitro 397
43 Down Syndrome and Acute Myeloid Leukemia: Lessons Learned from Experience with High-Dose Ara-C Containing Regimens 409
44 Cellular Drug Resistance in Childhood Acute Myeloid Leukemia: A Mini-Review with Emphasis on Cell Culture Assays 415
45 Is in Vitro Sensitivity of Blast-Cells Correlated to Therapeutic Effect in Childhood Acute Lymphoblastic Leukemia? 423
46 In Vitro Cytotoxic Drug Activity and in Vivo Pharmacokinetics in Childhood Acute Myeloid Leukemia 429
47 Prognosis in Adult AML Is Precisely Predicted by the Disc-Assay Using the Chemosensitivity-Index C[subscript 1] 437
48 Drug Resistance Testing of Acute Myeloid Leukemia in Adults Using the MTT Assay 445
49 MTT Assay for Drug Resistance in Childhood Acute Leukemia and Effect of Cyclosporin and Interferon: A Preliminary Report 453
50 Differential Antileukemic Activity of Prednisolone and Dexamethasone in Freshly Isolated Leukemic Cells 459
51 Activity of Vinorelbine on B-Chronic Lymphocytic Leukemia Cells in Vitro 473
52 Studies of Some Mechanisms of Drug Resistance in Chronic Myeloid Leukemia (CML) 477
53 Clinical Sensitivity to Anthracyclines in Ph/BCR+ Acute Lymphoblastic Leukemia 489
54 Differential Kinetics of Drug Resistance in Human Leukaemic Cells Measured by SCGE/CLSM 501
55 Demonstration of Differences in Drug Resistance by Direct Testing of DNA Excision Repair Activity following Standard and Liposomal Daunorubicin Exposure in Normal Pediatric Marrow Using High Resolution CLSM 509
56 Microsatellite Instability Assessment in Prediction of Drug Resistance in Childhood Burkitt's and Large Cell Diffuse Malignant Non-Hodgkin Lymphoma (MNHL) 517
57 High Resolution Confocal Laser Scanning Microscopy Analysis of DNA Excision Repair Capability in Small Volume Marrow Samples Exposed to DNA Directed Treatment Moieties 527
58 Defining the Optimal Dosage of Methotrexate for Childhood Acute Lymphoblastic Leukemia: New Insights from the Lab and Clinic 537
59 Mechanisms of Methotrexate Resistance in Acute Leukemia: Decreased Transport and Polyglutamylation 543
60 Lack of Cross-Resistance between Prednisolone and Methotrexate in Childhood Acute Lymphoblastic Leukemia? A Preliminary Analysis 551
61 New Developments in the Treatment of Acute Myeloid Leukemia 557
62 Aphidicolin Markedly Increases the in Vitro Sensitivity to Ara-C of Blast Cells from Patients with AML 567
63 Common Resistance Mechanisms to Nucleoside Analogues in Variants of the Human Erythroleukemic Line K562 571
64 Expression of DNA Mismatch Repair Proteins in Acute Lymphoblastic Leukemia and Normal Bone Marrow 579
65 Effects of CSFS and Their Combinations with Chemotherapeutic Agents (Ch) on Leukemic Blasts (LB) in Children (MTT-Assay) 585
66 Glucocorticosteroid Therapy in Childhood Acute Lymphoblastic Leukemia 593
67 Glucocorticoid Induced Apoptosis in Leukemia 607
68 Glucocorticoid Resistance and the AP-1 Transcription Factor in Leukemia 615
69 The Three Asparaginases: Comparative Pharmacology and Optimal Use in Childhood Leukemia 621
Index 631
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