Marrow protection : transduction of hematopoietic cells with drug resistance genes

書誌事項

Marrow protection : transduction of hematopoietic cells with drug resistance genes

volume editor, Joseph R. Bertino

(Progress in experimental tumor research, vol. 36)

Karger, c1999

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注記

Includes bibliographical references and indexes

内容説明・目次

内容説明

Authored by experts in the field, this volume provides a comprehensive review of the problems and opportunities in gene therapy focusing on the use of various drug resistance genes to provide protection of hematopoietic cells against drug toxicity. General topics include basic principles of gene transfer, optimizing conditions for gene transfer in hematopoietic cells, and gene transfer in the nonmyeloablated host. Specific chapters describe constructions and preclinical studies of specific genes that impart resistance to anticancer drugs when expressed in hematopoietic cells including MDR-1, mutated forms of human methylguanine-DNA-methyltranferase, mutant forms of dihydrofolate reductase and thymidylate synthase, dihydropyrimidine dehydrogenase and cytidine deaminase. For successful transfer of drug resistance genes, the possibility that they may be used as selectable markers and that marrow ablation may not be required are important considerations. This book is especially timely, as clinical trials with these drug resistance genes are expected to increase markedly in the next few years. It should appeal to all interested in stem cell biology and gene therapy, as well as clinicians who look forward to using this technology in their practice.

目次

  • Basic principles of gene transfer in haematopoietic stem cells
  • optimizing conditions for gene transfer into human haematopoietic cells
  • transfer of the MDR-1 gene into haematopoietic cells
  • O-benzylguanine-resistant mutant MGMT genes improve haematopoietic cell tolerance to alkylating agents
  • use of variants of dihydrofolate reductase in gene transfer to produce resistance to methotrexate and trimetrexate
  • augmentation of methotrexate resistance with co-expression of metabolically related genes
  • protection of bone marrow cells from toxicity of chemotherapeutic agents targeted toward thymidylate synthase by transfer of mutant forms of human thymidylate synthase cDNA
  • dihydropyrimidine dehydrogenase and resistance to 5-flourouracil
  • chemoprotection against cytosine nucleoside analogs using the human cytidine deaminase gene
  • in vivo selection of genetically modified bone marrow cells
  • gene transfer in the nonmyeloablated host.

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