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

Gene Therapy volume 24, pages 199–207 (2017)Cite this article

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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.

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Acknowledgements

We thank Dr Yongqiang Liao for his assistance in pathology evaluation. This work was supported by the National Natural Science Foundation of China grant 81402580, 81370461 and 81272681.

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Author notes

  1. W Zhou and S Dai: These authors contributed equally to this work.

Authors and Affiliations

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

    W Zhou, S Dai, H Zhu, Z Song, C He & X Huang

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

    W Zhou, S Dai, H Zhu, Z Song, X Hu & C He

  3. Department of Biochemistry and Molecular Medicine, The George Washington University Medical School, Washington, DC, USA

    Y Cai, J B Lee & Z Li

  4. Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    B Fang

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Correspondence to X Huang.

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Zhou, W., Dai, S., Zhu, H. et al. Telomerase-specific oncolytic adenovirus expressing TRAIL suppresses peritoneal dissemination of gastric cancer. Gene Ther 24, 199–207 (2017). https://doi.org/10.1038/gt.2017.2

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