title: Enhanced inhibition of thymidylate synthase by 5-fluorouracil and [6S]leucovorin combination therapy for breast cancer.
abstract: The influence of the addition of [6S]leucovorin (LV) to 5-fluorouracil (5-FU) preoperative chemotherapy was examined in patients with surgically resectable breast cancer who had had no prior treatment. The patients underwent one of the following three treatments at their will: (1) 5-FU 500 mg/m2 administered by an i.v. bolus; (2) [6S]LV 250 mg/m2 infused intravenously over two hours, with 5-FU 500 mg/m2 as an IV bolus at the midpoint of [6S]LV infusion, (3) no drug treatment. Tumors were resected 24 hours after the dose of 5-FU with or without [6S]LV. These studies confirmed an increased stabilization of 5-fluorodeoxyuridine monophosphate (FdUMP)-thymidylate synthase(TS)-folate ternary complex with the addition of [6S]LV. An increase of total TS activity was also found.
authors.affiliation: Department of Surgery, Tokyo Metropolitan Komagome Hospital, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tominaga
authors.forename: M
authors.initials: M
authors.lastname: Toi
authors.forename: T
authors.initials: T
authors.lastname: Shirasaka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*
chemical_list: D013940:Thymidylate Synthase; D002955:Leucovorin; D005472:Fluorouracil