Biochemical Modulation at the present time defines an area of study in which the intracellular metabolism of a given anti cancer agent is modulated (usually by a noncytotoxic agent or a cytotoxic agent at sufficiently low dosage to make it non cytotoxic) in order to either increase the effectiveness of the particular agent against tumor cells or decrease its cytotox icity against normal cells. The major focus of modulation has been the agents 5-fluorouracil (FUra), arabinofuranosylcytosine (ara-C), methotrexate (MTX) and a few alkylating agents. The major thrust of the studies has been to increase the flow of the anticancer agent along the pathway responsible for the formation of the cytotoxic species: for example, FUra to FUTP or ara-C to ara-CTP. While in most cases the application of research re sults to clinical trials does not require the subsequent exper tise of the laboratory researchers, application of biochemical modulatory schemes to clinical protocols necessitate a dramatic break with the past procedures. As shown in the laboratory clinical loop below, close collaboration between the laboratory and clinical investigator is essential. While the laboratory REDEFINE TECHNOLOGY, TESTS OR QUESTIONS FOR FURTHER THERAPEUTIC ADVANCE CLINICAL EXPERIMENTAL PROTOCOL (LABORATORY) RESEARCH STUDIES DEFINE AND TEST APPROPRIATE SCIENTIFIC PARAMETERS results define rationally-based regimens, it is essential that the clinical protocols contain the requirement that clinical material (either tumor or normal tissues) be sampled to deter mine whether the biochemical modulation being proposed is in fact beinq accomplished.
Erscheinungsdatum: 30.09.2011

lgrsnf/A:\compressed\10.1007%2F978-1-4613-2331-0.pdf

nexusstc/Biochemical Modulation of Anticancer Agents: Experimental and Clinical Approaches: Proceedings of the 18th Annual Detroit Cancer Symposium Detroit, Michigan, USA — June 13–14, 1986/607c71c5ef0eae21b1ecb603fda7dc49.pdf

zlib/Medicine/Randall Johnson, Fred Valeriote (auth.), Frederick A. Valeriote, Laurence H. Baker (eds.)/Biochemical Modulation of Anticancer Agents: Experimental and Clinical Approaches: Proceedings of the 18th Annual Detroit Cancer Symposium Detroit, Michigan, USA — June 13–14, 1986_2138482.pdf

Frederick A. Valeriote; L.O. Baker

Detroit Cancer Symposium

Nijhoff ; Distributors for North America, Kluwer Academic Publishers

Developments in oncology, 47, Boston, Norwell, Mass., USA, ©1986

United States, United States of America

Springer Nature, New York, NY, 2012

Sep 30, 2011

1, 2011

lg984556

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Source title: Biochemical Modulation of Anticancer Agents: Experimental and Clinical Approaches (Developments in Oncology)

Front Matter....Pages i-xvii
Biochemical Modulation of Anticancer Agents: An Overview....Pages 1-21
Biochemical Loci for Modulation of 5-Fluorouracil Activity....Pages 23-42
Biochemical Modulation of 5-Fluorouracil with Pyrimidines, Purines and their Nucleosides....Pages 43-64
Biochemical Modulation of Pyrimidine Pools for Enhancement of Antipyrimidine Cytotoxicity....Pages 65-91
Modulation of 5-Fluorouracil Cytotoxicity by Intracellular Pools of 5-Phosphoribosyl-1-Pyrophosphate (PRPP)....Pages 93-105
Biochemical Rationale for Selectivity in the Modulation of Methotrexate Activity During Leucovorin Rescue or Early Nucleoside Protection....Pages 107-129
Clinical Aspects of FUra Metabolism....Pages 131-152
Metabolic Modulation of Ara-C....Pages 153-170
Enhancement of Alkylating Agent Cytotoxicity by Radiation Sensitizers....Pages 171-189
Modulation of Alkylating Agents by Radiation Sensitizers— Clinical Aspects....Pages 191-203
The Role of Cellular Glutathione in Response of Tumor Cells to Radiation and Drugs....Pages 205-244
Modulation of Intracellular Levels of Glutathione....Pages 245-275
Glutathione Depletion with Buthionine Sulfoximine: Potential Clinical Applications....Pages 277-293
Modification of Cell Sensitivity to Anticancer Agents by Polyenes....Pages 295-323
Modulation of the Efflux of Anticancer Agents....Pages 325-341
Problems in the Clinical Evaluation of Biochemical Modulation Therapy....Pages 343-350

Proceedings of the 18th Annual Detroit Cancer Symposium, Detroit, Michigan, USA, June 13-14, 1986

2013-08-01