微波消融治疗肝癌对肝脏灌注和转移的影响及其机制的实验研究

Percutaneous microwave cancer treatment（PMCT） play a key role in the management of hepatocellular carcinoma (HCC). Microwave ablation seem to have potential to overcome the limitations of radiofrequency ablation and warrant further investigation.Many patients underwent the ablation operations were selected by surgery.Lacking the in-depth research ,the impacts and the mechanisms of microwave ablation to the hepatoma with metastasis of different period were still unknown. The outcomes of this study are eagerly awaited, because they have the potential to revolutionize the treatment of HCC.In this subject,we established a Buffalo rat model with McA-RH7777 cell line expressing GFP orthotopic implanted in left lobe of liver and then practiced the complete or partial microwave ablation.The liver perfusion and metastasis of the treated groups and the blank group were observed by 640 slices CT perfusion imaging , fluorescence microscopy before and after treatment and compared with pathological examination.After that,the metastasis of major organs and overall survival of the animals were calculated. Then the residual tumor and/or the peripherial tissue were detected by tissue microarray to find the related proteins and genes.These imformations would be investigated on Data Mining Technology and verified by in vitro and in vivo tests.Thus we can improve the therapeutic effect and avoid the over-treatment of microwave ablation in hepatoma.

微波消融（PMCT）是早中期肝癌的重要的局部微创治疗手段。消融治疗的病例大部分是外科手术后有了转移的病人,其对不同阶段的转移的影响尚未深入研究。了解消融治疗对肿瘤转移的影响及机制有助于选择最佳的治疗时机、方法和预防肝内外肿瘤转移。本课题先对绿色荧光蛋白(GFP)标记McA-RH7777 肝癌细胞在Buffalo大鼠肝脏原位种植瘤实施部分或完全微波消融，通过640层CT灌注成像与活体荧光成像和病理对照等方法来提升对微波消融治疗后局部组织灌注及微环境改变的认识，并与转移形成和生存期作相关对照，确认微波消融治疗与转移的互动影响及其机理，通过组织微阵列技术（tissue microarray）检测瘤周组织筛选出影响肝癌转移和消融疗效的重要蛋白基因数据并验证，在改进微波消融治疗疗效的同时避免过度治疗。

微波消融（PMCT）是早中期肝癌的重要的局部微创治疗手段。消融治疗的病例大部分是外科手术后有了转移的病人,其对不同阶段的转移的影响尚未深入研究。了解消融治疗对肿瘤转移的影响及机制有助于选择最佳的治疗时机、方法和预防肝内外肿瘤转移。本课题先对绿色荧光蛋白(GFP)标记McA-RH7777 肝癌细胞在Buffalo大鼠肝脏原位种植瘤实施部分或完全微波消融，通过MR小b值（b=50）DWI成像与活体荧光成像和病理对照等方法来提升对微波消融治疗后局部组织灌注及微环境改变的认识，并与转移形成和生存期作相关对照，总结肿瘤模型发展各个时期并模拟临床肿瘤进展各时期以便于展开各期研究，确认热消融治疗与转移的互动影响及其机理，经体内外实验证实不完全消融可能促进转移，需要联合其他有效治疗。通过iTRAQ及定向蛋白组学方法检测瘤周组织筛选出影响肝癌转移和消融疗效的重要蛋白数据，通过通路数据库检索鉴定，生物信息学分析并进行了体内外实验验证，我们找到APOE蛋白及YWHAE蛋白两个主要差异蛋白可能成为潜在治疗靶点，希望通过进一步实验确立新的联合治疗靶点，在改进微波消融治疗疗效的同时避免过度治疗。