Circulating endothelial progenitor cells in metronomic chemotherapy using irinotecan and/or bevacizumab for colon carcinoma: Study of their clinical significance
Circulating endothelial progenitor cells in metronomic chemotherapy using irinotecan and/or bevacizumab for colon carcinoma: Study of their clinical significance
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DOI：
10.3892/etm.2011.253
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发表时间：
2011-07-01
影响因子：
2.7
通讯作者：
Shirouzu, Kazuo
中科院分区：
文献类型：
--
作者：
Murakami, Hidetsugu;Ogata, Yutaka;Shirouzu, Kazuo
本研究的目的是阐明伊立替康（CPT-11）联合或不联合贝伐单抗对结肠癌节拍化疗的抗肿瘤疗效，以及循环内皮细胞（CEC）和内皮祖细胞（CEP）作为节拍化疗替代标志物的意义。将KM12SM细胞植入裸鼠皮下组织。确认植入肿瘤已长至5 mm后，A组每两周腹腔注射40 mg/kg CPT-11，持续4周[常规最大耐受剂量（MTD）]，B组每周两次10 mg/kg（节律），C组每周两次10 mg/kg联合5 mg/kg贝伐单抗每周两次（节律+抗血管生成），对照组每周接受 0.2 ml PBS。评估外周血中CEC和CEP的连续变化以及肿瘤组织中的微血管密度（MVD）。结果显示，B组和C组的抗肿瘤活性显着高于A组。与对照组相比，节律治疗B组和C组在第15天的CEPs有显着抑制，而在第4天和第8天，各组之间的CECs和CEPs没有显着差异。节拍组在第15天的MVD显着低于A组。或不使用贝伐珠单抗治疗结肠癌比 MTD 疗法通过抗血管生成作用更有效。 CEP 的连续测量可能是结肠癌节拍治疗疗效的预测因素和最佳剂量的决定性因素。
The aim of the present study was to clarify the antitumor efficacy of metronomic chemotherapy using irinotecan (CPT-11) combined with or without bevacizumab against colon cancer, and the significance of circulating endothelial cell (CECs) and endothelial progenitor cells (CEPs) as a surrogate marker for metronomic chemotherapy. KM12SM cells were implanted into the subcutis of nude mouse. After confirming that the implanted tumors had grown 5 mm in size, group A received an intraperitoneal injection of 40 mg/kg CPT-11 every two weeks for 4 weeks [conventional maximum-tolerated dose (MTD)], group B received 10 mg/kg twice weekly (metronomic), group C received 10 mg/kg twice weekly combined with 5 mg/kg bevacizumab twice weekly (metronomic + anti-angiogenic), and the control group received 0.2 ml of PBS every week. Serial changes of CECs and CEPs in peripheral blood and microvessel density (MVD) in the tumor tissues were evaluated. The results showed that the antitumor activity in group B and in group C was significantly higher than that in group A. A significant inhibition in CEPs on day 15 in the metronomic therapy groups B and C was noted when compared to that in the control group, while there was no significant difference in CECs and CEPs between the groups on days 4 and 8. The MVD on day 15 in metronomic groups was significantly lower than that in group A. In conclusion, metronomic chemotherapy of CPT-11 with or without bevacizumab for colon cancer was more effective than the MTD therapy via anti-angiogenic effects. Sequential measurement of CEPs may be a predictive factor for the efficacy and a decisive factor for the optimal dose of metronomic therapy in colon cancer.