Research for the purpose of introduction in clinical use of molecular target and antiangiogenic cancer therapy combined with ultrasound energy

旨在介绍分子靶向和抗血管生成癌症治疗与超声能量相结合的临床应用的研究

基本信息

批准号：
20300182
负责人：
EMOTO Makoto
金额：
$ 12.31万
依托单位：
International University of Health and Welfare (2011)Fukuoka University (2008-2010)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2011
项目状态：
已结题

项目摘要

Metronomic chemotherapy is the frequent administration of low doses of chemotherapeutic agents targeting tumor-associated endothelial cells. We examined the efficacy of metronomic irinotecan combined with low-intensity ultrasound (US) in human uterine sarcoma and evaluated its antiangiogenesis mechanism by measuring the circulating endothelial progenitor cells (CEP), a surrogate marker of angiogenesis. A human uterine sarcoma cell line, FU-MMT-3, was used in the present study because this tumor is one of the most malignant neoplasms of human solid tumors and it also has a high angiogenesis property. The combination of low dose irinotecan and US irradiation significantly inhibited the tube formation of HUVEC and vascular endothelial growth factor expression of tumor cells in vitro. The FU-MMT-3 xenografts in nude mice were treated using US at a low intensity (2.0 w/cm2,1 MHz) for 4 min three times per week each after the intraperitoneal administration of irinotecan; this treatment was continued for 5 weeks. The tumor vascularity was assessed by contrastenhanced color Doppler US in real time. The combination treatment significantly inhibited the mobilization of CEP and intratumoral vascularity compared with the control. This combination therapy showed a significant reduction in tumor volume, resulting in a significant prolongation of survival, in comparison with each treatment alone. These results suggest that the effect of metronomic chemotherapy for human uterine sarcoma was accelerated by US irradiation in vivo and this combination might therefore be potentially effective for new cancer therapy.

计量化疗是经常施用靶向肿瘤相关内皮细胞的低剂量化学治疗剂。我们检查了人子宫肉瘤中的水平伊立替康的功效，并结合了低强度超声（US），并通过测量循环的内皮祖细胞（CEP）（CEP）（一种血管生成的替代标志物），评估了其抗高基因生成机制。本研究中使用了人子宫肉瘤细胞系FU-MMT-3，因为该肿瘤是人类实体瘤的最恶性肿瘤之一，并且具有较高的血管生成特性。低剂量伊立替康和美国辐射的组合显着抑制了HUVEC和血管内皮生长因子在体外的表达的结合。在腹膜内给药后，使用低强度（2.0 W/cm2,1 MHz）每周3次使用我们以低强度（2.0 W/cm2,1 MHz）处理裸鼠的FU-MMT-3异种移植物；这种治疗持续了5周。肿瘤血管是通过实时对比的颜色多普勒对比评估的。与对照相比，组合处理显着抑制了CEP和肿瘤内血管的动员。与单独的每种治疗相比，这种组合疗法显示肿瘤体积显着减少，导致生存的显着延长。这些结果表明，在体内辐射可以加速计量化疗对人子宫肉瘤的影响，因此这种组合可能对新的癌症治疗有效。