Kinoshita Shigeki, Hirai Ryuji, Yamano Toshihisa, Yuasa Ichiro, Tsukuda Kazunori, Shimizu Nobuyoshi
Department of Surgical Oncology and Thoracic Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Surg Today. 2004;34(1):40-6. doi: 10.1007/s00595-003-2645-9.
We investigated the suppressive effect of the angiogenesis inhibitor TNP-470 on accelerated hepatocellular carcinoma (HCC) growth in the regenerating liver.
After 70% partial hepatectomy (PH), AH-130 cells were injected into the portal vein of Donryu rats. A control group was given the vehicle only, and the treated group was given 10 mg/kg TNP-470 subcutaneously every second day, from 24 h after tumor implantation, seven times. On day 14, tumor growth was evaluated by the number of foci on the liver surface, liver weight, and the microvessel density of the tumor.
The number of foci was significantly less in the treated group (116.5 +/- 103.1) than in the control group (319.3 +/- 223.1) ( P < 0.05), as was microvessel density, which was 31.3 +/- 14.0/mm2 in the treated group and 61.2 +/- 18.9/mm2 in the control group ( P < 0.05). The liver tended to weigh less in the treated group (12.15 +/- 1.28 g) than in the control group (15.22 +/- 5.35 g). We also assessed whether TNP-470 retards liver regeneration. Seven days after 70% PH, the liver weight in the treated group was similar to that in the control group. Total bilirubin, serum glutamic oxaloacetic transaminase, and serum glutamic pyruvic transaminase were not higher in the treated group than in the control group.
TNP-470 can suppress HCC growth without retarding liver regeneration after PH.
我们研究了血管生成抑制剂TNP - 470对再生肝中加速生长的肝细胞癌(HCC)的抑制作用。
在70%部分肝切除术(PH)后,将AH - 130细胞注入到Donryu大鼠的门静脉。对照组仅给予赋形剂,治疗组从肿瘤植入后24小时开始,每隔一天皮下注射10mg/kg TNP - 470,共七次。在第14天,通过肝脏表面的病灶数量、肝脏重量和肿瘤的微血管密度来评估肿瘤生长情况。
治疗组的病灶数量(116.5±103.1)明显少于对照组(319.3±223.1)(P<0.05),微血管密度也是如此,治疗组为31.3±14.0/mm²,对照组为61.2±18.9/mm²(P<0.05)。治疗组的肝脏重量(12.15±1.28g)倾向于比对照组(15.22±5.35g)轻。我们还评估了TNP - 470是否会延缓肝脏再生。70%PH术后7天,治疗组的肝脏重量与对照组相似。治疗组的总胆红素、血清谷草转氨酶和血清谷丙转氨酶均不高于对照组。
TNP - 470可抑制HCC生长,且不延缓PH术后的肝脏再生。