Titlebook: Concepts, Mechanisms, and New Targets for Chemotherapy; F. M. Muggia Book 1995 Springer Science+Business Media New York 1995 DNA.breast ca

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冬眠

Recent clinical advances with camptothecin analoguesn, demonstrated encouraging activity in early clinical testing but was abandoned due to unpredictable toxicity. In 1985, Hsaing and Liu observed that the cytotoxic effect of camptothecin requires the nuclear enzyme topoisomerase I [2]. This finding coincided with the development of the semisynthetic

Delude

The reversal of multidrug resistanceaboratory, tumor cells can be selected for resistance to a particular cytotoxin by repeated exposure to that drug. The selected cells often display crossresistance to a number of functionally and structurally distinct drugs. This drug-resistant phenotype is referred to as . (MDR). Currently, the bes

Implicit

Fluoropyrimidine catabolismtes for important enzymatic reactions required in vital cell biologic processes, e.g., synthesis of DNA and RNA. Several reviews on the metabolism of antimetabolite drugs have recently been published, providing a general background on these drugs [1–5]. The pyrimidine antimetabolite drugs consist of

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Aspects of one-carbon folate cycling related to fluoropyrimidine and antifolate therapyxyuridylate (FdUMP) inhibition of thymidylate synthase (TS) occurs by the ordered, sequential binding of TS, FdUMP, and then 5-10-methylenetetrahydrofolate (CH.FH.) [.–.]. In cell-free kinetic systems, CH.FH. must be in excess for maximal TS-FdUMP-CH.FH. ternary complex formation and complete inhibi

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predict

High-dose chemotherapy with peripheral blood progenitor autograftinglinic, this strategy also results in increased toxicity to normal tissues. For those cytotoxics that are primarily dose-limited by myelosuppression (e.g., alkylating agents, carboplain, and etoposide), the use of autologous bone marrow transplantation (ABMT) has facilitated substantial dose escalati