title: [Anti-angiogenic activities of UFT and its metabolites, GHB and GBL, in the dorsal air sac (DAS) model in mice].
abstract: We investigated the effects of UFT and its metabolites, GHB and GBL, on angiogenesis induced by tumor cells in a dorsal air sac (DAS) assay in mice. Five tumor cell lines (murine renal carcinoma; RENCA, human gastric cancer; 4-1ST, human small-cell lung carcinoma; LX-1, and human colon carcinoma; DLD-1, KM-20C) were used in the DAS assay. In this model, UFT demonstrated a significant anti-angiogenic activity in a dose-dependent manner while 5-FU (19 mg/kg/day) and 5'-DFUR (200 mg/kg/day) were less effective. Moreover, tegafur (FT), a component of UFT, and gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL), in vivo metabolites of UFT, inhibited angiogenesis induced by RENCA cells. The inhibitory effects of 5-FU, GHB, and GBL on angiogenesis were increased with administration by continuous infusion, providing a suitable pharmacokinetic profile. These results suggest that GHB and GBL are involved in the expression of anti-angiogenic activity of UFT.
authors.affiliation: Cancer Research Laboratory, Hanno Research Center, Taiho Pharmaceutical Co., Ltd.
authors.forename: Y
authors.initials: Y
authors.lastname: Basaki
authors.forename: K
authors.initials: K
authors.lastname: Yonekura
authors.forename: L
authors.initials: L
authors.lastname: Chikahisa
authors.forename: S
authors.initials: S
authors.lastname: Okabe
authors.forename: A
authors.initials: A
authors.lastname: Hashimoto
authors.forename: K
authors.initials: K
authors.lastname: Miyadera
authors.forename: K
authors.initials: K
authors.lastname: Aoyagi
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D015107:4-Butyrolactone / Q000378:metabolism; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000473:pathology; D008175:Lung Neoplasms / Q000098:blood supply* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D012978:Sodium Oxybate / Q000378:metabolism; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000473:pathology; D005641:Tegafur / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014498:Uracil / Q000378:metabolism / Q000494:pharmacology
chemical_list: D005641:Tegafur; D014498:Uracil; D012978:Sodium Oxybate; D015107:4-Butyrolactone