te Velde E A, Vogten J M, Gebbink M F G B, van Gorp J M, Voest E E, Borel Rinkes I H M
Department of Surgery and Laboratory of Medical Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Br J Surg. 2002 Oct;89(10):1302-9. doi: 10.1046/j.1365-2168.2002.02183.x.
Tumour-induced microvascular networks have become attractive targets in cancer therapy. Strategies that target both tumour cells and vasculature have not been investigated in models of early metastatic colorectal disease. The efficacy of a combination of conventional chemotherapy with a potent angiogenesis inhibitor (endostatin or angiostatin) in a murine model of early colorectal liver metastasis was studied.
Sixty-six mice were subjected to intrasplenic injection of C26 tumour cells to induce colorectal liver metastases. Control animals received phosphate-buffered saline (n = 8) or citrate buffer (n = 8). Treatment included conventional chemotherapy (n = 9), endostatin (n = 8), high-dose (n = 5) or low-dose (one-tenth of optimal dose; n = 10) angiostatin, as well as the combination of either of these drugs with chemotherapy (n > 5). Clinical appearance was scored daily using a semiquantitative scale. Liver weight, macroscopic and histological tumour involvement (hepatic replacement area; HRA) were measured upon death at day 12.
Treated mice displayed significantly better clinical scores than controls, except for those animals treated with low-dose angiostatin with or without chemotherapy. Treatment with conventional chemotherapy resulted in a decrease in HRA from 42.3 to 29.1 per cent (P < 0.001). The addition of angiostatin or endostatin to conventional chemotherapy improved antitumoral efficacy, in a multiplicative manner, resulting in a HRA of approximately 3.5 per cent (P < 0.001).
The addition of angiostatin or endostatin to conventional chemotherapy enhanced antitumoral efficacy in a murine model of early colorectal liver metastasis.
肿瘤诱导的微血管网络已成为癌症治疗中具有吸引力的靶点。在早期转移性结直肠癌模型中，尚未对同时靶向肿瘤细胞和脉管系统的策略进行研究。本研究探讨了在小鼠早期结直肠癌肝转移模型中，传统化疗与强效血管生成抑制剂（内皮抑素或血管抑素）联合使用的疗效。
66只小鼠接受脾内注射C26肿瘤细胞以诱导结直肠癌肝转移。对照动物接受磷酸盐缓冲盐水（n = 8）或柠檬酸盐缓冲液（n = 8）。治疗包括传统化疗（n = 9）、内皮抑素（n = 8）、高剂量（n = 5）或低剂量（最佳剂量的十分之一；n = 10）血管抑素，以及这些药物中的任何一种与化疗联合使用（n > 5）。每天使用半定量量表对临床表现进行评分。在第12天处死时测量肝脏重量、宏观和组织学肿瘤累及情况（肝替代面积；HRA）。
除了接受低剂量血管抑素单独或联合化疗的动物外，治疗组小鼠的临床表现评分明显优于对照组。传统化疗使HRA从42.3%降至29.1%（P < 0.001）。在传统化疗中添加血管抑素或内皮抑素可成倍提高抗肿瘤疗效，使HRA约为3.5%（P < 0.001）。
在小鼠早期结直肠癌肝转移模型中，在传统化疗中添加血管抑素或内皮抑素可增强抗肿瘤疗效。
