Enhanced radioresponse with a novel recombinant human endostatin protein via tumor vasculature remodeling: Experimental and clinical evidence
Enhanced radioresponse with a novel recombinant human endostatin protein via tumor vasculature remodeling: Experimental and clinical evidence
复制标题
新型重组人内皮抑素蛋白通过肿瘤血管重塑增强放射反应：实验和临床证据
DOI：
10.1016/j.radonc.2012.10.022
复制
发表时间：
2013-01-01
影响因子：
5.7
通讯作者：
Lu, You
中科院分区：
文献类型：
--
作者：
Meng, Mao-Bin;Jiang, Xiao-Dong;Lu, You
Purpose: This study aimed to examine the effect of the novel recombinant human endostatin (rh-Endo) protein on tumor vasculature, and to explore and evaluate the optimal scheduling of rh-Endo and radiotherapy (RT).Methods: Tumor-perfusion parameters and hypoxia were monitored after rh-Endo treatment in 10 nonsmall cell lung-cancer (NSCLC) patients. Eight-week female C57BL/6J mice were randomized to receive rh-Endo or control (saline) once daily for 12 days when Lewis lung carcinoma (LLC) reached approximately 100-150 mm(3). On planned days, tumors were measured for cell apoptosis, microvessel density, pericytes, blood-vessel morphology, and tumor hypoxia. The tumor response under different combinations of rh-Endo and RT schedules was evaluated.Results: Tumor hypoxia was significantly reduced 5 days after rh-Endo in NSCLC patients, and a similar result was found in the LLC mouse model. The anti-tumor effect was markedly enhanced when RT was administered within the remodeling period compared to any other treatment schedule. rh-Endo treatment remodeled the tumor vasculature after 5 days by reducing microvessel density and increasing pericytic coverage of the vessel endothelium.Conclusion: This study demonstrated decreased hypoxia in animals and patients upon rh-Endo treatment, which also enhanced the radioresponse within the vasculature-remodeling period. The optimal clinical combination of rh-Endo and RT warrants further investigation. (c) 2012 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 106 (2013) 130-137
