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Telomerase-specific oncolytic virotherapy for human hepatocellular carcinoma

机译:端粒酶特异性溶瘤病毒疗法治疗人肝细胞癌

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摘要

AIM: To evaluate the therapeutic efficiency of replicative adenovirus CNHK300 targeted in telomerase-positive hepatocellular carcinoma.METHODS: CNHK300, ONYX-015 (55 kDa protein deleted adenovirus) and wtAd5 (wild type adenovirus 5) were compared, and virus proliferation assay, cell viability assay, Western blot and fluorescence microscopy were used to evaluate the proliferation and cytolysis selectivity of CNHK300.RESULTS: The replicative multiples in Hep3B and HepGII after 48 h of CNHK300 proliferation were 40 625 and 65 326 fold, respectively, similar to that of wtAd5.. However, CNHK300 exhibited attenuated replicative ability in normal fibroblast cell line BJ. CNHK300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI.CONCLUSION: CNHK300 is a cancer-selective replication-competent adenovirus which can cause oncolysis of liver cancer cells as well as wtAd5 (wild type adenovirus 5), but had severely attenuated replicative and cytolytic ability in normal cells. This novel strategy of cancer treatment offers a promising treatment platform.
机译:目的:评估端粒酶阳性肝细胞癌中复制型腺病毒CNHK300的治疗效果。方法:比较CNHK300,ONYX-015(缺失55 kDa蛋白的腺病毒)和wtAd5(野生型腺病毒5),并进行病毒增殖试验,细胞结果:CNHK300增殖48小时后,Hep3B和HepGII中的复制倍数分别为40 625倍和65 326倍,与wtAd5相似。但是,CNHK300在正常成纤维细胞系BJ中显示出减弱的复制能力。 CNHK300可以以低感染复数(MOI)裂解肝癌细胞,但即使在MOI高的情况下也不能影响正常细胞的生长。结论:CNHK300是一种具有癌症选择性复制能力的腺病毒,可引起肝癌细胞的溶瘤。以及wtAd5(野生型腺病毒5),但在正常细胞中的复制和细胞溶解能力大大减弱。这种新颖的癌症治疗策略提供了有希望的治疗平台。

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