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Antitumor activity of an hTERT promoter-regulated tumor-selective oncolytic adenovirus in human hepatocellular carcinoma
  • ISSN号:1007-9327
  • 期刊名称:《世界胃肠病学杂志:英文版》
  • 时间:0
  • 分类:R735.7[医药卫生—肿瘤;医药卫生—临床医学]
  • 作者机构:[1]Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China, [2]Xinyuan Institute of Medicine and Biotechnology,College of Life Science, Zhcjiang Sci-T~ch University, Hangzhou 310018, Zhejiang Province, China, [3]Changhai Hospital, Second Military Medical University, Shanghai 200438, China, [4]Jiangsu Key Laboratory for Molecular and Medical Bioteclmology, Life Science College, Nanjing Normal University, Nanjing 210097, Jiangsu Province, China
  • 相关基金:Supported by the Natural Science Foundation of China, No. 30572149; the National 863 High Technology R&D Project of China, No. 2003AA216030
中文摘要:

瞄准:构造肿瘤选择的复制能干的侵入人体气管粘膜的病菌(RCAd ) , SG300,用人的 telomerase 颠倒 transcriptase (hTERT ) 的一个修改倡导者。方法:在 hepatocellular 癌的 SG300 的 Theantitumor 功效在 vitro 并且在 vivo 被估计。在由 MTT 的 vitrocell 生存能力,试金被用来估计肿瘤选择的 oncolysis 和安全特征 ofSG300,并且在 vivo 反肿瘤, SG300 的活动在裸体老鼠在确定的 hepatocellular 癌模特儿被估计。结果:SG300 能在感染(MOI ) 的低复合的细胞溶解 hepatocellular 癌房间,但是不能甚至在高 MOI 影响正常房间的生长。两个都,在 hepatocellular 癌的 Hep3Band SMMC-7721 异种皮移植模特儿,, SG300 有明显的反肿瘤效果,导致在肿瘤体积的减少。它到肿瘤房间的选择 oncolysis 和到正常房间的安全比 ONYX-015 的也优异。肿瘤标本的病理学的检查显示出在癌症房间有选择地复制并且导致了癌症房间的 apoptosis 和坏死的那 SG300。结论:调整倡导者的 replicative 侵入人体气管粘膜的病菌 SG300 有的 hTERT 一个 bettercancer 选择的复制能干的能力,和罐头明确地与积极 telomerase 活动杀死大量癌症房间,并且因此为指向治疗 ofhepatocellular 有更好的潜力癌。

英文摘要:

AIM: To construct a tumor-selective replicationcompetent adenovirus (RCAd), SG300, using a modified promoter of human telomerase reverse transcriptase (hTERT). METHODS: The antitumor efficacy of SG300 in hepatocellular carcinoma was assessed in vitro and in vivo. In vitro cell viability by MTT assay was used to assess the tumor-selective oncolysis and safety features of SG300, and in vivo antitumor activity of SG300 was assessed in established hepatocellular carcinoma models in nude mice. RESULTS: SG300 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. Both in Hep3B and SMMC-7721 xenograft models of hepatocellular carcinoma, SG300 had an obvious antitumor effect, resulting in a decrease in tumor volume. Its selective oncolysis to tumor cells and safety to normal cells was also superior to that of ONYX-015. Pathological examination of tumor specimens showed that SG300 replicated selectively in cancer cells and resulted in apoptosis and necrosis of cancer cells. CONCLUSION: hTERT promoter-regulated replicative adenovirus SG300 has a better cancer-selective replication-competent ability, and can specifically kill a wide range of cancer cells with positive telomerase activity, and thus has better potential for targeting therapy of hepatocellular carcinoma.

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  • 《世界胃肠病学杂志:英文版》
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  • 主办单位:百世登出版集团有限公司
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  • 国际标准刊号:ISSN:1007-9327
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