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[干扰素α-A/D与氟嘧啶衍生物在肾包膜下试验中的联合效应]

[Combined effects of interferon alpha-A/D with fluoropyrimidine derivatives in the subrenal capsule assay].

作者信息

Nishiyama M, Takagami S, Kirihara Y, Saeki T, Niimi K, Kim R, Jinushi K, Toge T, Niimoto M, Hattori T

机构信息

Dept. of Surgery, Hiroshima University.

出版信息

Gan To Kagaku Ryoho. 1988 Aug;15(8):2285-90.

PMID:3136700
Abstract

The combined effects of interferon alpha-A/D (IFN alpha-A/D) with 5-fluorouracil and fluoropyrimidine derivatives such as 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur), UFT, 1-hexylcarbamoyl-5-fluorouracil (HCFU) and 5'-deoxy-5-fluorouracil (5'-DFUR), were examined by 4-day subrenal capsule assay. Four human tumor xenografts serially transplanted in athymic mice, H-111, SH-10 established from gastric cancers, CH-4 and CH-5 from colon cancers, were used. In this experiment, the adequate dose of each agent was estimated as 50 mg/kg for 5-FU, 473 mg/kg for tegafur, 433 mg/kg for UFT, 50 mg/kg for HCFU, 185 mg/kg for 5'-DFUR and 1 x 10(5) IU for IFN alpha-A/D, respectively. When synergistic, additive and subadditive effects were defined as positive combined effects, all combinations produced positive combined effects against H-111 and CH-5, while negative ones were observed for all combinations against CH-4. The combinations of 5-FU, HCFU and 5'-DFUR with IFN alpha-A/D produced synergistic effects against SH-10. These results indicate that the combination therapy of 5-FU and fluoropyrimidine derivatives with IFN alpha-A/D would be useful.

摘要

通过4天的肾包膜下移植试验,研究了α-A/D干扰素(IFNα-A/D)与5-氟尿嘧啶及氟嘧啶衍生物(如1-(2-四氢呋喃基)-5-氟尿嘧啶(替加氟)、优福定、1-己基氨基甲酰基-5-氟尿嘧啶(HCFU)和5'-脱氧-5-氟尿嘧啶(5'-DFUR))的联合效应。使用了在无胸腺小鼠中连续传代移植的4种人肿瘤异种移植瘤,分别是源自胃癌的H-111、SH-10,以及源自结肠癌的CH-4和CH-5。在本实验中,每种药物的合适剂量分别估计为:5-氟尿嘧啶50mg/kg、替加氟473mg/kg、优福定433mg/kg、HCFU50mg/kg、5'-DFUR185mg/kg以及IFNα-A/D1×10⁵IU。当协同、相加和次相加效应被定义为阳性联合效应时,所有组合对H-111和CH-5均产生阳性联合效应,而对CH-4的所有组合均观察到阴性联合效应。5-氟尿嘧啶、HCFU和5'-DFUR与IFNα-A/D的组合对SH-10产生协同效应。这些结果表明,5-氟尿嘧啶和氟嘧啶衍生物与IFNα-A/D的联合治疗可能是有效的。

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