The angiogenesis inhibitor TNP-470 (AGM-1470) improves long-term survival of rats with liver metastasis
The angiogenesis inhibitor TNP-470 (AGM-1470) improves long-term survival of rats with liver metastasis
复制标题
DOI：
10.1006/jsre.1996.0303
复制
发表时间：
1996-07-15
影响因子：
2.2
通讯作者：
Baba, S
中科院分区：
文献类型：
--
作者：
Ahmed, MH;Konno, H;Baba, S
血管生成抑制剂对肿瘤的生长或转移有很好的治疗作用，但这些药物的持续抗转移作用尚未得到研究。我们研究了血管生成抑制剂TNP-470对大鼠腹水肝癌AH-130细胞门脉内移植后肝转移的持续作用。TNP470以15 mg/kg(L-TNP)或30 mg/kg(H-TNP)隔日皮下注射，连续2周。治疗14天后，与对照组(300.7+/-100.7)相比，L-TNP组(85·1+/-77·6)和H-TNP组(31·7+/-49·6)的肝转移数均显著减少(P<0·01)。尽管对照组大鼠在肝转移后1个月内全部死亡，但L-TNP和H-TNP在4个月时的存活率分别为82%和60%(P<；0.001)。低剂量的TNP470无毒性，无腹膜或胸膜内出血，有助于L TNP组较好的预后。有趣的是，在存活4个月的15只大鼠中，只有1只发现了小的休眠转移灶，而在治疗结束时，所有的大鼠都观察到了转移灶。这些结果表明，TNP-470对血管内皮细胞的持续细胞抑制作用可能有助于通过减少转移负担来提高长期存活率。(C)1996年学术出版社。
An excellent therapeutic effect of angiogenesis inhibitors on tumor growth or metastasis has been reported, but the sustained antimetastatic effect of these agents has not been studied. We investigated the sustained effect of TNP-470, an angiogenesis inhibitor, in rats with hepatic metastasis following intraportal implantation of rat ascites hepatoma AH-130 cells. TNP-470 was administered subcutaneously at 15 mg/kg (L-TNP) or 30 mg/kg (H-TNP) on alternate days for 2 weeks. The number of liver metastases was significantly reduced in both the L-TNP (85.1 +/- 77.6) and H-TNP (31.7 +/- 49.6) groups compared to the control group (300.7 +/- 100.7) (P < 0.01) at 14 days after the start of treatment. Although all rats in the control group died within 1 month of massive liver metastasis, the L-TNP and H-TNP, respectively, had a survival rate of 82 and 60%, at 4 months (P < 0.001). Absence of toxicity of TNP-470 at the lower dose, as evidenced by the absence of intraperitoneal or intrapleural bleeding, contributed to a better prognosis in the L-TNP group. Interestingly, a small dormant metastatic focus was found in only 1 of 15 rats surviving for 4 months, whereas metastatic foci were observed in all rats at the end of treatment. These results suggest that the sustained cytostatic effect of TNP-470 on vascular endothelial cells may help to improve long-term survival by reducing the metastatic burden. (C) 1996 Academic Press, Inc.