Basaki Y, Shibata J, Murakami K, Hashimoto A, Yonekura K, Fukushima M, Yamada Y
Cancer Research Laboratory, Hanno Research Center, Taiho Pharmaceutical Co., Ltd.
Gan To Kagaku Ryoho. 1999 Oct;26(11):1607-12.
We investigated the effect of UFT on a pulmonary metastasis after excision of the primary lesion, which was induced by implantation of murine renal carcinoma cells, RENCA. The cells were implanted into the left kidney of Balb/cA mice, and nephrectomy of the left kidney with a primary tumor was performed on day 10 after implantation. Administration of antitumor drugs, was started on day 13 [UFT (20 mg/kg, p.o., 5'-DFUR (24.6 mg/kg, p.o.), 5-FU (19 mg/kg, i.v.), TNP-470 (30 mg/kg, s.c.)]. In this metastasis model, the estimated mean survival time of the control group was 41.3 +/- 2.9 days. A significant life-prolonging effect was observed for UFT and 5-FU (T/C: 160.8%, 125.7%, respectively). An inhibitory effect on the growth of metastatic tumors in the lung was detected for both UFT and TNP-470 (TWI: 55.5%, 48.7%, respectively), but not 5'-DFUR. In a dorsal air sac (DAS) model, UFT abrogated angiogenesis induced by RENCA in a dose-dependent manner. These data suggest that the life-prolonging effect of UFT results from the continuous exposure of a tumor to its cytotoxic effects and anti-angiogenic activity.
我们研究了优福定（UFT）对由小鼠肾癌细胞RENCA植入诱导的原发性病变切除术后肺转移的影响。将这些细胞植入Balb/cA小鼠的左肾，并在植入后第10天对患有原发性肿瘤的左肾进行肾切除术。在第13天开始给予抗肿瘤药物[优福定（20mg/kg，口服）、5'-去氧氟尿苷（24.6mg/kg，口服）、5-氟尿嘧啶（19mg/kg，静脉注射）、TNP-470（30mg/kg，皮下注射）]。在这个转移模型中，对照组的估计平均生存时间为41.3±2.9天。观察到优福定和5-氟尿嘧啶有显著的延长生命作用（T/C分别为160.8%、125.7%）。检测到优福定和TNP-470对肺转移瘤的生长均有抑制作用（TWI分别为55.5%、48.7%），但5'-去氧氟尿苷没有。在背气囊（DAS）模型中，优福定以剂量依赖的方式消除了RENCA诱导的血管生成。这些数据表明，优福定的延长生命作用源于肿瘤持续暴露于其细胞毒性作用和抗血管生成活性。
