Factors that influence the therapeutic activity of 5-fluorouracil [6RS]leucovorin combinations in colon adenocarcinoma xenografts.

摘要: The therapeutic activity of FUra alone or combined with [6RS]LV doses ranging from 50 to 1,000 mg/m2 was examined in eight colon adenocarcinoma xenografts, which five were established adult neoplasms (HxELC2, HxGC3, HxVRC5, HxHC1, and HxGC3/c1TK-c3 selected for TK deficiency) three derived adolescent tumors (HxSJC3A, HxSJC3B, HxSJC2). growth-inhibitory effects potentiated by higher (500–1,000 mg/m2) lines (HxGC3/c1TK-c3, HxSJC3A, HxSJC3B) a low dose only one tumor (HxVRC5). Expansion pools CH2−H4PteGlun+H4PteGlun (≥2.4-fold) response obtained all except HxHC1. Metabolism high levels 5-CH3−H4PteGlu being detected, but not CH=H4PteGlu+10-CHO−H4PteGlu remained relatively low. In the tumors, those following administration. CH2−H4Pte-Glun+H4PteGlun significantly expanded, concentrations lower than observed other two lines. sensitivity FUra±[6RS]LV characteristics [6S]LV metabolism did correlate CH=H4PteGlu synthetase, enzyme responsible initial cellular CH=H4PteGlu. Thus, no single metabolic phenotype correlated [6RS]LV-induced expansion pools. Potentiation efficacy HxGC3c1TK-c3 xenografts parent HxGC3 demonstrating influence dThd salvage capability FUra-[6RS]LV combinations. Plasma CBA/CaJ mice (1.1 μm). present data therefore demonstrate importance (1) [6RS]LV, (2) CH2−H4PteGlun+H4PteGlun, (3) potentiation xenogafts. plasma achieved are presented.