Mugitani T, Taniguchi H, Takada A, Yamaguchi A, Masuyama M, Hoshima M, Takahashi T
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Br J Cancer. 1998 Feb;77(4):638-42. doi: 10.1038/bjc.1998.102.
We examined hepatic artery ligation combined with an angiogenesis inhibitor, TNP-470, in the treatment of VX2 tumour inoculated into the liver of rabbits. Effects on tumour growth were correlated with arterial collateral development in this system. Three treatment methods were compared: (1) the left hepatic artery was ligated at the liver hilum (ligation group); (2) TNP-470 (40 mg per body) was infused continuously for 7 days via the common hepatic artery (TNP group); (3) the left hepatic artery was ligated and TNP-470 was infused continuously for 7 days via the common hepatic artery (ligation + TNP group). These treatments were started 12-14 days after tumour inoculation. The day of initiating treatment was defined as day 0. Although there were no significant differences in tumour volume among the three treated groups on day 7 after treatment, tumour volumes in the ligation + TNP group were significantly smaller than in the ligation group and the TNP group on day 14 after treatment. The vasculature and arterial collaterals around the tumour were demonstrated by the perfusion of a silicon rubber solution, Microfil. In the ligation + TNP group, the new microvasculature around the tumour decreased compared with the ligation group. The TNP-470 inhibition of microvascular proliferation may limit the development of collaterals that communicate with new feeding arteries. These results suggest that transarterial embolization combined with TNP-470 may enhance the anti-tumour effect of transarterial embolization alone in the treatment of liver tumours.
我们研究了肝动脉结扎联合血管生成抑制剂TNP - 470对接种于兔肝脏的VX2肿瘤的治疗效果。在该系统中，对肿瘤生长的影响与动脉侧支循环的发展相关。比较了三种治疗方法：（1）在肝门处结扎左肝动脉（结扎组）；（2）经肝总动脉连续7天输注TNP - 470（每只动物40mg）（TNP组）；（3）结扎左肝动脉并经肝总动脉连续7天输注TNP - 470（结扎+TNP组）。这些治疗在肿瘤接种后12 - 14天开始。开始治疗的当天定义为第0天。尽管治疗后第7天三个治疗组的肿瘤体积无显著差异，但治疗后第14天，结扎+TNP组的肿瘤体积明显小于结扎组和TNP组。通过灌注硅橡胶溶液Microfil显示肿瘤周围的脉管系统和动脉侧支。与结扎组相比，结扎+TNP组肿瘤周围的新生微血管减少。TNP - 470对微血管增殖的抑制作用可能会限制与新供血动脉相通的侧支循环的发展。这些结果表明，经动脉栓塞联合TNP - 470可能会增强单纯经动脉栓塞在肝肿瘤治疗中的抗肿瘤效果。
