Möller P H, Ivarsson K, Roos G, Radnell M, Persson B, Tranberg K G, Stenram U
Department of Surgery, University of Lund, University Hospital, Sweden.
Anticancer Res. 1997 Jul-Aug;17(4A):2401-6.
Transient hepatic arterial occlusion causes necrosis in solid hepatic tumors in the rat, but regrowth of tumor cells and capillaries takes place from the tumor periphery. It was therefore considered of interest to combine this treatment with the angiogenesis inhibitor TNP-470 (therapeutic model). Wistar rats with a dimethylhydrazine-induced adenocarcinoma implanted into the liver received one of the following treatments: TNP-470 + transient hepatic ischemia, transient hepatic ischemia alone, TNP-470 alone or sham solution alone. Rats were sacrificed one week after the start of treatment. In addition, we investigated if TNP-470 decreases the risk of tumor take in the liver after intraportal injection of viable tumor cells (adjuvant study). Transient hepatic ischemia combined with TNP-470 gave a smaller increase in tumor volume than transient hepatic ischemia (p < 0.01), TNP-470 (p < 0.001) alone or no treatment (p < 0.001). Transient hepatic ischemia or TNP-470 caused a significant suppression of tumor growth when compared to controls (p < 0.01 in both cases). In the adjuvant study, TNP-470 caused retardation of tumor growth (p < 0.01 as compared to controls) but did not affect tumor number. It is concluded that TNP-470 suppressed tumor growth, both alone and in combination with transient hepatic ischemia, but did not affect take of tumor.
短暂性肝动脉闭塞可导致大鼠实体肝肿瘤发生坏死，但肿瘤细胞和毛细血管会从肿瘤周边重新生长。因此，将这种治疗方法与血管生成抑制剂TNP - 470相结合（治疗模型）被认为是有意义的。将二甲基肼诱导的腺癌植入肝脏的Wistar大鼠接受以下治疗之一：TNP - 470 + 短暂性肝缺血、单纯短暂性肝缺血、单纯TNP - 470或单纯假手术溶液。治疗开始一周后处死大鼠。此外，我们研究了TNP - 470是否能降低门静脉注射活肿瘤细胞后肝脏肿瘤发生的风险（辅助研究）。与单纯短暂性肝缺血（p < 0.01）、单纯TNP - 470（p < 0.001）或不治疗（p < 0.001）相比，短暂性肝缺血联合TNP - 470导致肿瘤体积增加较小。与对照组相比，短暂性肝缺血或TNP - 470均显著抑制了肿瘤生长（两种情况均p < 0.01）。在辅助研究中，TNP - 470导致肿瘤生长延迟（与对照组相比p < 0.01），但不影响肿瘤数量。结论是，TNP - 470单独或与短暂性肝缺血联合使用时均能抑制肿瘤生长，但不影响肿瘤发生。
