Konno H
Second Department of Surgery, Hamamatsu University School of Medicine, Japan.
Cancer Chemother Pharmacol. 1999;43 Suppl:S85-9. doi: 10.1007/s002800051104.
The antitumor and antimetastatic effects of TNP-470, an angiogenesis inhibitor, on human gastrointestinal tumors xenotransplanted into nude mice were investigated. When two gastric cancer (MT-2 and MT-5) and two colon cancer (TK-4 and TK-13) xenografts are transplanted orthotopically into nude mice, liver metastasis develops 6 weeks after transplantation. TNP-470 30 mg/kg had a significant inhibitory effect on primary tumor growth of gastric cancers when given on alternate days from 7 days after transplantation. However, when given from 10 days or 14 days after transplantation, no inhibitory effect on the growth of any tumor xenograft was observed. In contrast, liver metastasis of each xenograft type was inhibited significantly by TNP-470. The effect of TNP-470 on prognosis was investigated using a hepatic metastatic model of rat hepatoma. Although all untreated rats that received AH-130 cell implants died within one month of massive hepatic metastasis, >50% of rats treated with TNP-470 survived for 4 months. The number of apoptotic cells in hepatic metastatic foci was significantly increased by TNP-470 administration. These results suggest that TNP-470 may provide a new approach to the treatment of digestive organ malignancies.
研究了血管生成抑制剂TNP-470对移植到裸鼠体内的人胃肠道肿瘤的抗肿瘤和抗转移作用。将两种胃癌（MT-2和MT-5）和两种结肠癌（TK-4和TK-13）异种移植物原位移植到裸鼠体内后，移植6周后会发生肝转移。从移植后7天开始隔天给予30 mg/kg的TNP-470对胃癌的原发肿瘤生长具有显著抑制作用。然而，从移植后10天或14天开始给药时，未观察到对任何肿瘤异种移植物生长的抑制作用。相比之下，TNP-470可显著抑制每种异种移植物类型的肝转移。使用大鼠肝癌肝转移模型研究了TNP-470对预后的影响。尽管所有接受AH-130细胞植入的未治疗大鼠在发生大量肝转移后的一个月内死亡，但接受TNP-470治疗的大鼠中有超过50%存活了4个月。给予TNP-470后，肝转移灶中的凋亡细胞数量显著增加。这些结果表明，TNP-470可能为消化器官恶性肿瘤的治疗提供一种新方法。
