Download Biochemical Modulation of Anticancer Agents: Experimental by Randall Johnson, Fred Valeriote (auth.), Frederick A. PDF

By Randall Johnson, Fred Valeriote (auth.), Frederick A. Valeriote, Laurence H. Baker (eds.)

Biochemical Modulation this present day defines a space of research within which the intracellular metabolism of a given anti­ melanoma agent is modulated (usually by way of a noncytotoxic agent or a cytotoxic agent at sufficiently low dosage to make it non­ cytotoxic) so that it will both raise the effectiveness of the actual agent opposed to tumor cells or lessen its cytotox­ icity opposed to common cells. the most important concentration of modulation has been the brokers 5-fluorouracil (FUra), arabinofuranosylcytosine (ara-C), methotrexate (MTX) and some alkylating brokers. the most important thrust of the experiences has been to extend the movement of the anticancer agent alongside the pathway accountable for the formation of the cytotoxic species: for instance, FUra to FUTP or ara-C to ara-CTP. whereas quite often the appliance of analysis re­ sults to medical trials doesn't require the following exper­ tise of the laboratory researchers, software of biochemical modulatory schemes to scientific protocols necessitate a dramatic holiday with the prior approaches. As proven within the laboratory­ medical loop less than, shut collaboration among the laboratory and medical investigator is key. whereas the laboratory REDEFINE expertise, assessments OR QUESTIONS FOR additional healing strengthen medical EXPERIMENTAL PROTOCOL (LABORATORY) examine reviews outline AND attempt acceptable clinical PARAMETERS effects outline rationally-based regimens, it really is crucial that the medical protocols include the requirement that scientific fabric (either tumor or basic tissues) be sampled to discourage­ mine no matter if the biochemical modulation being proposed is in reality beinq accomplished.

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Extra info for Biochemical Modulation of Anticancer Agents: Experimental and Clinical Approaches: Proceedings of the 18th Annual Detroit Cancer Symposium Detroit, Michigan, USA — June 13–14, 1986

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Cancer Res. 25:21, 1984. Danenberg PV, Lockshin A: Fluorinated pyrimidines as tightbinding inhibitors of thymidylate synthetase. Pharmac. Ther. 13:69-90, 1981. Evans RM, Laskin JD, Hakala MT: Assessment of growthlimiting events caused by 5-fluorouracil in mouse cells and in human cells. Cancer Res. 40:4113-4122, 1980. Laskin JD, Evans RM, Slocum HD et al: Basis for natural variation in sensitivity to 5-fluorouracil in mouse and human cells in culture. Cancer Res. 39:383-390, 1979. Woodcock TM, Martin DS, Damin LAM et al: Combination clinical trials with thymidine and fluorouracil: A Phase I and clincial pharmacologic evaluation.

J. Ca. 47:387-392, 1983. Stewart FA, Rojas A: Radioprotection of mouse skin by WR-2721 in single and fractionated treatments. Brit. J. Radiol. 55:42-47, 1982. Travis EL: The oxygen dependence of protection by aminothio1s: Implications for normal tissues and solid tumors. Int. J. Radiat. Oncol. BioI. Phys. 10:1495-1501, 1984. Radiation-Protective Drugs and Their Reaction Mechanisms. Livesey JC, Reed OJ, Adamson LF (eds), Noyes Publications, New Jersey, 1985. Valeriote F, Tolen S: Protection and potentiation of nitrogen mustard cytotoxicity by WR-2721.

If treatment failure in the clinic is due to the emergence of drug-resistant tumor cell populations in many patients, biochemical modulation will 18 not delay tumor recurrence unless it deals specifically with the resistance mechanism(s) responsible. If a leukemia fails to respond to cytarabine because a deoxycytidine kinase-deficient cell population has emerged, modulation of dCTP pools will have little effect on response. If relapse of small cell lung cancer is due to the emergence of a cell population with increased DNA repair capability and/or mutation in the gene for topoisomerase II such that it is no longer sensitive to epipodophyllotoxins or anthracyclines, modulation of drug uptake or slight dosage escalation by protection of normal tissues is unlikely to be of much value.

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