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首页> 外文期刊>Radiotherapy and oncology: Journal of the European Society for Therapeutic Radiology and Oncology >Enhanced radioresponse with a novel recombinant human endostatin protein via tumor vasculature remodeling: Experimental and clinical evidence
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Enhanced radioresponse with a novel recombinant human endostatin protein via tumor vasculature remodeling: Experimental and clinical evidence

机译：通过肿瘤血管重构，用新型重组人内皮抑素蛋白增强放射反应：实验和临床证据

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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 non-small 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 mm3. 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. ? 2013 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology.
机译：目的：本研究旨在检查新型重组人内皮抑素（rh-Endo）蛋白对肿瘤脉管系统的作用，并探索和评估rh-Endo和放疗（RT）的最佳时间表。方法：对10例非小细胞肺癌（NSCLC）患者进行rh-Endo治疗后，监测其肿瘤灌注参数和缺氧情况。当Lewis肺癌（LLC）达到约100-150 mm3时，将八周的雌性C57BL / 6J小鼠随机接受rh-Endo或对照（盐水）治疗12天，每天一次。在计划的日子里，测量肿瘤的细胞凋亡，微血管密度，周细胞，血管形态和肿瘤缺氧。评价了rh-Endo和RT方案不同组合下的肿瘤反应。结果：rh-Endo后5天，NSCLC患者的肿瘤缺氧明显减少，在LLC小鼠模型中也发现了类似的结果。与其他任何治疗方案相比，在重塑期内进行RT时，抗肿瘤作用显着增强。 rh-Endo治疗在5天后通过降低微血管密度和增加血管内皮细胞的周细胞覆盖率来重塑肿瘤血管。结论：这项研究表明，rh-Endo治疗后动物和患者的缺氧减少，这也增强了脉管系统重塑期内的放射反应。 rh-Endo和RT的最佳临床组合值得进一步研究。 ？ 2013 Elsevier Ireland Ltd.保留所有权利。放射疗法和肿瘤学。

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