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首页> 外文期刊>癌と化学療法 >Benefits of TS-1 plus leucovorin combination therapy for colorectal cancer: evaluation of therapeutic effect of TS-1 and leucovorin combination therapy using rodent model fed a low folate diet
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Benefits of TS-1 plus leucovorin combination therapy for colorectal cancer: evaluation of therapeutic effect of TS-1 and leucovorin combination therapy using rodent model fed a low folate diet

机译：TS-1加亚叶酸钙联合疗法治疗结直肠癌的益处：用低叶酸饮食的啮齿动物模型评价TS-1和亚叶酸钙素联合疗法的治疗效果

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We evaluated the therapeutic effect of TS-1, a novel oral fluoropyrimidine, in combination with leucovorin with in vivo experiments using a murine tumor xenograft model fed a low folate diet. The reduced folate levels in the tumors of mice fed a low folate diet were significantly lower than those in the tumors of mice fed a normal diet. In addition, the basal reduced folate levels in the tumors of mice fed a low folate diet were comparable to those in human colorectal cancer tissues. Furthermore, when leucovorin was orally administered, the reduced folate levels in the tumors of mice fed a low folate diet were more than two-fold higher than those of mice fed the normal diet. The leucovorin-induced potentiation of TS-1 antitumor activity was obviously higher in COL-1 tumor-bearing mice fed a low folate diet than in mice fed a normal diet. The remarkable increase in reduced folate levels following the administration of leucovorin contributed to the leucovorin-induced potentiation of TS-1 antitumor activity in this low-folate-diet animal model. These results suggest that rodent models fed a low folate diet are suitable for in vivo evaluation of reduced folate drugs like leucovorin. In this model, the combination of leucovorin with TS-1 resulted in a higher antitumor efficacy than TS-1 alone or the combination of UFT and leucovorin, suggesting that TS-1 and leucovorin combination therapy may be an effective regimen for patients with colorectal cancer.
机译：我们使用低叶酸饮食的鼠类肿瘤异种移植模型，在体内实验中评估了TS-1（一种新型口服氟嘧啶）与亚叶酸的治疗效果。低叶酸饮食的小鼠肿瘤中降低的叶酸水平显着低于正常饮食的小鼠肿瘤中降低的叶酸水平。此外，饲喂低叶酸饮食的小鼠肿瘤中的基础叶酸水平降低与人结肠直肠癌组织中的水平相当。此外，当口服亚叶酸钙时，饲喂低叶酸饮食的小鼠的肿瘤中降低的叶酸水平是饲喂正常饮食的小鼠的两倍以上。低叶酸饮食的含COL-1荷瘤小鼠中，亚叶酸钙诱导的TS-1抗肿瘤活性明显高于正常饮食的小鼠。在这种低叶酸饮食动物模型中，施用亚叶酸钙后降低的叶酸水平显着增加，有助于亚叶酸素诱导的TS-1抗肿瘤活性增强。这些结果表明，饲喂低叶酸饮食的啮齿动物模型适合体内评估还原叶酸药物（如亚叶酸钙蛋白）。在该模型中，亚叶酸和TS-1的联合使用比单用TS-1或UFT和亚叶酸的联合治疗具有更高的抗肿瘤功效，这表明TS-1和亚叶酸的联合治疗可能是结直肠癌患者的有效方案。

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