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Books > Medicine > Clinical & internal medicine > Diseases & disorders > Oncology
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Novel Approaches to Selective Treatments of Human Solid Tumors - Laboratory and Clinical Correlation (Paperback, Softcover reprint of the original 1st ed. 1993)
Loot Price: R1,596
Discovery Miles 15 960
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Novel Approaches to Selective Treatments of Human Solid Tumors - Laboratory and Clinical Correlation (Paperback, Softcover reprint of the original 1st ed. 1993)
Series: Advances in Experimental Medicine and Biology, 339
Expected to ship within 10 - 15 working days
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The therapeutic efficacy of FUra has been attributed to its
incorporation into cellular RNA and, to its inhibition of
thymidylate synthase, leading to potent inhibition of DNA synthesis
and DNA damage. Studies of cell lines in vitro and model systems in
vivo have demonstrated that although mechanisms of sensitivity and
resistance to FUra are multifactorial, in the presence of
citrovorum factor (LV, CF, 5-formyltetrahydrofolate) the site of
action of FUr a becomes predominantly the pronounced and prolonged
inhibition of thymidylate synthase. This action is the result of
stabilization of the covalent ternary complex between FdUMP, an
active metabolite of FUr a, 5, IO-methylenetetrahydrofolates, and
thymidylate synthase. This effect of LV is thus an example of the
concept of metabolic modulation. CF is commercially available as a
racemic mixture of diastereoisomers (6R and 6S). The 6R isomer is
considered to be biologically inactive; the 6S isomer is the
biologically active form that is metabolized intracellularly to'
form the various folate cofactor pools including 5,
IO-methylenetetrahydrofolates. Although the extent of metabolism of
folates in normal and tumor tissues has not been clearly
delineated, it has been determined that the formation of
folypolyglutamates is primarily a function of schedule of CF
administration, while the retention of significant concentrations
of reduced folate is a function of the dose and also the schedule
of LV. Thus, it appears that for optimal modulation of FUra
activity several factors must be considered simultaneously.
General
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