[Theoretical basis for low-dose CDDP/5-FU therapy].
The theoretical basis for low-dose cisplatin (CDDP)/5-fluorouracil (5-FU) therapy is rather clear. CDDP can inhibit methionine-uptake into tumor cells and cause depletion of folate cofactors including 5-CH3FH4 and FH4, which are essential for the formation of a ternary complex with thymidylate synthetase and 5-fluorodeoxyuridine, an active metabolite of 5-FU. The literature on this mechanism are reviewed herein, and the methionine-dependency of human cancer xenografts and the modulation of 5-FU-cytotoxicity through methionine-depletion are reported.
Kubota
T
T
Dept. of Surgery, School of Medicine, Keio University.
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy; D002945:Cisplatin / Q000008:administration & dosage; D003110:Colonic Neoplasms / Q000188:drug therapy; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy
D008715:Methionine; D002945:Cisplatin; D005472:Fluorouracil