Dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine S-1 may be effective against peritoneal dissemination in gastric cancer.
Dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine S-1 may be effective against peritoneal dissemination in gastric cancer.
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二氢嘧啶脱氢酶抑制性氟嘧啶 S-1 可能有效对抗胃癌的腹膜播散。
DOI：
10.3892/or.12.5.973
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发表时间：
2004
期刊：
影响因子：
4.2
通讯作者：
K. Hirakawa
中科院分区：
文献类型：
--
作者：
Shigehito Yamagata;B. Nakata;K. Hirakawa
研究了新型口服氟嘧啶衍生物S-1对胃癌腹膜转移的影响。OCUM-2 MD 3细胞是一种高度腹膜转移的细胞系，将其注射到裸鼠体内。将这些小鼠分配至以下三组（每组，n=10）：S-1组，每日经口给予10 mg/kg体重的S-1; FT组，每日经口给予100 mg/kg体重的替加氟（FT）;对照组，未给予抗癌药物。接种后第二天开始给药。S-1组的中位生存时间显著长于FT组（30天vs.23天; P<0.005）和对照组（vs.24天; P<0.005）。S-1组1-4 h腹水中5-FU浓度平均值为414-580 ng/ml（n=5），FT组为70-87 ng/ml（n =5），两组在各观察时间点均有显著性差异。S-1组在给药后1-6 h观察到腹水中高浓度的CDHP。DPD在腹膜转移灶周围的纤维组织中呈强阳性表达，而在腹膜转移灶本身的肿瘤细胞中呈弱阳性表达。S-1给药后5-FU在腹腔中的高浓度和长持续时间表明，S-1可能对腹膜播散有效。高浓度的CDHP可阻止5-FU在腹膜播散及其周围纤维组织中的降解。
The effects of a novel oral fluoropyrimidine derivative S-1 on peritoneal metastasis from gastric cancer were investigated. OCUM-2MD3 cells, a highly peritoneal-metastatic cell line, were injected intraperitoneally in nude mice. These mice were allocated to the following three groups (each group, n=10): the S-1 group, to which 10 mg/kg body weight of S-1 was administered per os daily; the FT group, to which 100 mg/kg body weight of tegafur (FT) was administered per os daily; the control group, to which no anticancer drug was administered. Drug administration was starting the day after inoculation. The median survival time of the S-1 group was found to be significantly longer than that of the FT group (30 days vs. 23 days; P<0.005) and the control group (vs. 24 days; P<0.005). The mean values of 5-fluorouracil (5-FU) concentrations in ascites of the S-1 group at 1-4 h were 414-580 ng/ml (n=5), and those of FT group were 70-87 ng/ml (n=5), with significant differences between the two groups at each observation time. The high CDHP concentrations in ascites of the S-1 group were observed at 1-6 h after drug administration. DPD was expressed strongly in fibrous tissue around peritoneal metastasis and weakly in tumor cells of peritoneal metastasis themselves. The high concentrations and long duration of 5-FU in the peritoneal cavity after S-1 administration suggest that S-1 may be effective against peritoneal dissemination. High concentrations of CDHP may prevent 5-FU degradation in peritoneal dissemination and its surrounding fibrous tissue.