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Treatment of patient tumor-derived colon cancer xenografts by a TRAIL gene-armed oncolytic adenovirus

Cancer Gene Therapy volume 18, pages 336–345 (2011)Cite this article

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Abstract

Oncolytic virus-armed gene therapy may offer new treatment options and improve the prognosis for patients with colon cancer. In this study, we sought to further confirm the antitumor activity of oncolytic virus-armed tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene therapy in xenografts, which derived from the tumors of patients with colon cancer. To this end, we established xenotransplantable tumors from fresh surgical specimens. The histology of these xenografts maintained the features of the original tumors during passaging in nude mice. We next treated these xenografts with adenoviruses carrying TRAIL and the adenovirus E1A gene (Ad/TRAIL-E1) driven by the human telomerase reverse transcriptase promoter. The vector expressing the TRAIL gene (Ad/gTRAIL) or the E1A gene (Ad/GFP-E1) alone was used as control vector. The results demonstrated that Ad/TRAIL-E1 had more significant inhibitory effects on tumor growth than Ad/gTRAIL or Ad/GFP-E1 alone. Furthermore, we did not find any obvious treatment-related toxicity in the mice. Our results indicate that the use of an oncolytic adenoviral vector, in combination with TRAIL gene therapy, is a promising novel approach for cancer therapy.

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Acknowledgements

We thank Yongqiang Liao for expert technical assistance in histology. This work was supported in part by grants from the National Natural Science Foundation of China grant 30528030 and 30700970. This article represents a partial fulfillment of the requirements for a Ph.D. degree for Wei Zhou.

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Authors and Affiliations

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

    W Zhou, H Zhu, X Huang & C He

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

    W Zhou, H Zhu, W Chen, X Hu, X Pang, J Zhang, X Huang & C He

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

    B Fang

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Zhou, W., Zhu, H., Chen, W. et al. Treatment of patient tumor-derived colon cancer xenografts by a TRAIL gene-armed oncolytic adenovirus. Cancer Gene Ther 18, 336–345 (2011). https://doi.org/10.1038/cgt.2010.83

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  • DOI: https://doi.org/10.1038/cgt.2010.83

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