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Increased antitumor capability of fiber-modified adenoviral vector armed with TRAIL against bladder cancers

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Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Adenoviral vectors are widely used for cancer therapy and show a tumor-suppressing effect. However, bladder cancers are found to be resistant against infection of Ad5-derived adenoviral vector, limiting the application of the existing strategy of gene therapy. Therefore, efforts to develop novel types of adenoviral vector aimed for improving the viral infection and enhancing expression level of tumor-inhibiting transgene is urgently required. We constructed a 5/35 fiber-modified E1A-deleted adenoviral vector armed with TRAIL gene. Its ability to express this gene for inhibition of bladder cancer cell growth was investigated in our work. The results showed that this modification in fiber region facilitates adenoviral infection to bladder cancer, perhaps due to high expression of CD46 on target cell surface. Subsequently, we found an enhanced expression level of TRAIL mediated by 5/35 fiber-modified adenoviral vectors in bladder cancer cells, leading to an increased tumor-inhibiting capability of 5/35 adenoviral vector against bladder cancer cells. Consistently, growth of xenograft tumors in mice was also effectively inhibited by 5/35 fiber-modified vector-mediated gene therapy strategy. The 5/35 fiber-modified adenoviral vector-based gene transfer shows an improved efficacy against bladder cancers. The application of this novel gene therapy vector may benefit the patients in clinical bladder cancer treatment.

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Authors and Affiliations

  1. Department of Urology, General Hospital of Chengdu Military Area Command of Chinese PLA, Chengdu, 610083, Sichuan Province, People’s Republic of China

    Youguang Zhao, Qingtang Wang, Liang Wang & Hang Yang

  2. Department of Cardiology, General Hospital of Chengdu Military Area Command of PLA, Chengdu, 610083, Sichuan Province, People’s Republic of China

    Ying Li

  3. Group of Expert, General Hospital of Chengdu Military Area Command of PLA, Chengdu, 610083, Sichuan Province, People’s Republic of China

    Mingli Li

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  1. Youguang Zhao
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  2. Ying Li
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  3. Qingtang Wang
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  4. Liang Wang
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  5. Hang Yang
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  6. Mingli Li
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Correspondence to Youguang Zhao.

Additional information

Youguang Zhao and Ying Li contributed equally to this work.

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Zhao, Y., Li, Y., Wang, Q. et al. Increased antitumor capability of fiber-modified adenoviral vector armed with TRAIL against bladder cancers. Mol Cell Biochem 353, 93–99 (2011). https://doi.org/10.1007/s11010-011-0778-5

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  • DOI: https://doi.org/10.1007/s11010-011-0778-5

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