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Pre-clinical Experimental Study of Animal Irreversible Electroporation Treatment for Liver Cancer

NING Zhou-yu;WANG Peng;CHEN Hao;Fudan University Shanghai Cancer Center,Department of Oncology of Shanghai Medical College,Fudan University;  
[Purpose]To investigate the apoptosis of liver cancer after irreversible electroporation(IRE) operation,and to observe the antitumor effect and security of IRE technique for liver cancer xenograft,to provide experimental evidence for the clinical usage. [Methods] Twelve New Zealand white rabbit with liver cancer xenograft models were randomly divided into treatment group and control group. The treatment group received IRE,the control group received no treatment. Two rabbits in each group were executed on the 1st,3rd,5th,7th,14 th day after IRE. Liver and kidney function and creatine kinase were tested,ELISA method was used to detect CTn I,Caspase-3,TNF-α and VEGF levels in the plasma. TUNEL assay was used to detect the apoptosis of tumor tissue. Immunohistochemistry was applied to detect Bcl-2,HSP70 and VEGF expressions in liver cancer xenograft. [Results] During the treatment,the rabbits had pulse-type tremor,but it was controllable. Post-treatment serological test showed that serum amylase,liver and kidney functions were within the normal range except significant higher level of creatine kinase. ELISA detection of plasma showed IRE increasing secretion of Caspase-3, and TNF-α,while reducing VEGF expression,and no elevation of CTn I. HE staining showed a clear borderline between the necrotic and normal areas,with a large number of red blood cells and inflammatory cell infiltration on the edge. After 14 days of treatment,regeneration signs appeared in the target tumor tissues. TUNEL assay showed that IRE significantly increased the apoptosis in liver cancer xenograft cells compared with the control group. Immunohistochemistry results showed that IREdecreased the expressions of Bcl-2 and VEGF,increased HSP70 expression in liver cancer xenograft,and improved anti-tumor effect of IRE. [Conclusion] IRE might inhibit the growth of liver tumor via inhibiting angiogenesis,inducing apoptosis and producing specific anti-tumor immune response. IRE is a safe and effective approach for liver cancer. With the evidence from the experiment,this study may support further clinical IRE application.
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