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表达TRAIL的端粒酶特异性溶瘤腺病毒可抑制胃癌的腹膜播散。

Telomerase-specific oncolytic adenovirus expressing TRAIL suppresses peritoneal dissemination of gastric cancer.

作者信息

Zhou W, Dai S, Zhu H, Song Z, Cai Y, Lee J B, Li Z, Hu X, Fang B, He C, Huang X

机构信息

Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Key Laboratory of Biotherapy of Zhejiang province, Hangzhou, China.

出版信息

Gene Ther. 2017 Apr;24(4):199-207. doi: 10.1038/gt.2017.2. Epub 2017 Jan 11.

Abstract

Peritoneal dissemination is the most common condition of metastasis in gastric cancer. The survival duration of a patient with advanced stage gastric cancer, may be improved by gene therapy. In this study, we used an oncolytic adenovirus vector (Ad/TRAIL-E1) that expresses both the TRAIL and E1A genes under the control of a tumor-specific promoter. We evaluated the anti-tumor effect of Ad/TRAIL-E1 on gastric cancer cells in vitro, as well as in vivo in a xenograft peritoneal carcinomatosis mouse model. Our data showed that Ad/TRAIL-E1 induced TRAIL-mediated apoptosis in gastric cancer cell lines, but not in the normal cell lines. In addition, Ad/TRAIL-E1 significantly inhibited peritoneal metastasis and prolonged the survival of mice without treatment-related toxicity. Therefore, tumor-specific TRAIL expression from an oncolytic adenovirus vector may provide a novel therapeutic approach for the treatment of advance stage gastric cancer with peritoneal dissemination.

摘要

腹膜播散是胃癌最常见的转移情况。晚期胃癌患者的生存时长可通过基因治疗得到改善。在本研究中,我们使用了一种溶瘤腺病毒载体(Ad/TRAIL-E1),其在肿瘤特异性启动子的控制下表达TRAIL和E1A基因。我们评估了Ad/TRAIL-E1在体外对胃癌细胞的抗肿瘤作用,以及在异种移植腹膜癌病小鼠模型中的体内抗肿瘤作用。我们的数据表明,Ad/TRAIL-E1在胃癌细胞系中诱导了TRAIL介导的凋亡,但在正常细胞系中未诱导。此外,Ad/TRAIL-E1显著抑制了腹膜转移并延长了小鼠的生存期,且无治疗相关毒性。因此,来自溶瘤腺病毒载体的肿瘤特异性TRAIL表达可能为治疗伴有腹膜播散的晚期胃癌提供一种新的治疗方法。

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