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微秒级脉冲电场(μsPEFs)生物电消融对肝细胞癌进行局部区域治疗的临床前研究

Preclinical Study of Locoregional Therapy of Hepatocellular Carcinoma by Bioelectric Ablation with Microsecond Pulsed Electric Fields (μsPEFs).

作者信息

Chen Xinhua, Ren Zhigang, Li Chengxiang, Guo Fei, Zhou Dianbo, Jiang Jianwen, Chen Xinmei, Sun Jihong, Yao Chenguo, Zheng Shusen

机构信息

1] The Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China [2] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, 310003, China.

The State Key Laboratory of Power Transmission Equipment &System Security and New Technology, Chongqing University, Chongqing, 400030, China.

出版信息

Sci Rep. 2015 Apr 30;5:9851. doi: 10.1038/srep09851.

Abstract

Unresectable hepatocellular carcinoma (HCC) needs locoregional ablation as a curative or downstage therapy. Microsecond Pulsed Electric Fields (μsPEFs) is an option. A xenograft tumor model was set up on 48 nude mice by injecting human hepatocellular carcinoma Hep3B cells subcutaneously. The tumor-bearing mice were randomly divided into 3 groups: μsPEFs treated, sham and control group. μsPEFs group was treated by μsPEFs twice in 5 days. Tumor volume, survival, pathology, mitochondria function and cytokines were followed up. μsPEFs was also conducted on 3 swine to determine impact on organ functions. The tumors treated by μsPEFs were completely eradicated while tumors in control and sham groups grew up to 2 cm(3) in 3 weeks. The μsPEFs-treated group indicated mitochondrial damage and tumor necrosis as shown in JC-1 test, flow cytometry, H&E staining and TEM. μsPEFs activates CD56+ and CD68+ cells and inhibits tumor proliferating cell nuclear antigen. μsPEFs inhibits HCC growth in the nude mice by causing mitochondria damage, tumor necrosis and non-specific inflammation. μsPEFs treats porcine livers without damaging vital organs. μsPEFs is a feasible minimally invasive locoregional ablation option.

摘要

不可切除的肝细胞癌(HCC)需要局部消融作为一种根治性或降期治疗方法。微秒脉冲电场(μsPEFs)是一种选择。通过皮下注射人肝细胞癌Hep3B细胞,在48只裸鼠上建立了异种移植肿瘤模型。将荷瘤小鼠随机分为3组:μsPEFs治疗组、假手术组和对照组。μsPEFs组在5天内接受两次μsPEFs治疗。对肿瘤体积、生存期、病理学、线粒体功能和细胞因子进行随访。还对3头猪进行了μsPEFs治疗以确定对器官功能的影响。接受μsPEFs治疗的肿瘤被完全根除,而对照组和假手术组的肿瘤在3周内长至2 cm³。如JC-1试验、流式细胞术、苏木精-伊红染色和透射电子显微镜所示,μsPEFs治疗组显示出线粒体损伤和肿瘤坏死。μsPEFs激活CD56+和CD68+细胞并抑制肿瘤增殖细胞核抗原。μsPEFs通过引起线粒体损伤、肿瘤坏死和非特异性炎症来抑制裸鼠体内HCC的生长。μsPEFs治疗猪肝脏而不损伤重要器官。μsPEFs是一种可行的微创局部消融选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48f7/4415577/128602b56f0f/srep09851-f1.jpg

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