5-10-methylenetetrahydrofolic-acid has been researched along with Kidney-Neoplasms* in 1 studies
1 other study(ies) available for 5-10-methylenetetrahydrofolic-acid and Kidney-Neoplasms
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Pharmacologic rationale for fluoropyrimidine-leucovorin combination: biochemical mechanisms.
Fluoropyrimidines, 5-fluorouracil (5-FU), and 5-fluorodeoxyuridine (FdUrd) are effective inhibitors of DNA synthesis. Inhibitory action is potentiated both in vitro and in vivo by the addition of leucovorin (LV; either the natural [6S] isomer or the mixture of the unnatural and natural [6R,S] isomers). The inhibition of DNA is subsequent to thymidylate synthase inhibition mediated by the formation of a covalently bound ternary complex consisting of 5-fluorodeoxyuridine monophosphate, 5,10-methylenetetrahydrofolate, and thymidylate synthase. In vitro exposure of cells to varying concentrations of [6R,S]LV or [6S]LV increases intracellular pools of the reduced folate cofactor. The effect of [6S]LV is both dose and time dependent. The in vitro effective concentration of [6S]LV is approximately 1 to 10 mumol/L, depending on cell type. While HCT-8 cells demonstrated optimal modulation of 5-FU and FdUrd cytotoxicity with 1 mumol/L of [6S]LV for 5 hours, the SE cells required higher doses of LV and longer exposure time. Thus, dependent on the cell type, higher concentration (10 mumol/L) and duration of exposure (greater than 5 hours) may be essential for an effective modulation of fluoropyrimidine action. Clinically, to achieve the concentration and conditions found optimal in an in vitro system, a dose of 500 mg/m2 by 5-hour infusion appears to be the present optimal dose and schedule of [6R,S]LV administration in combination with 5-FU. Topics: Cecal Neoplasms; Drug Administration Schedule; Drug Synergism; Floxuridine; Humans; Ileal Neoplasms; Kidney Neoplasms; Leucovorin; Stereoisomerism; Tetrahydrofolates; Thymidylate Synthase; Tumor Cells, Cultured | 1992 |