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Reovirus decreases azoxymethane-induced aberrant crypt foci and colon cancer in a rodent model

Cancer Gene Therapy volume 14, pages 867–872 (2007)Cite this article

Abstract

Reovirus type 3 Dearing has demonstrated oncolytic efficacy in vitro and in vivo against a variety of cancer cell lines, tumor xenografts and syngeneic cancer models. In this study, we investigated the effectiveness of reovirus against aberrant crypt foci (ACF) and colon cancer induced by the carcinogen azoxymethane (AOM) in an immunocompetent rat model. Sprague–Dawley rats received 15 mg/kg AOM intraperitoneally once per week for 4 weeks and reovirus was administered rectally once a week for 5 weeks starting 20 weeks after the last dose of AOM. Two weeks after completion of reovirus therapy, animals were examined for tumor burden in the colon and other tissues. Reovirus-treated animals showed a decrease in total ACF numbers (P=0.014), in large ACFs (P=0.0069) and in tumor number (P=0.03) compared to vehicle-treated animals. Fewer obstructing tumors in the colon (P=0.07) and duodenum (P=0.03) and reduced hepatic metastases were also noted. In addition, a tumor cell line derived from hepatic metastases was found to be susceptible to reovirus in vitro. Our results show that repeated rectal reovirus administration had some efficacy in the treatment and prevention of AOM-induced ACFs, colon cancers and metastases.

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Acknowledgements

This work was supported in part by funds from the Canadian Institutes for Health Research (PB, PL, DM), the Alberta Cancer Board (RNJ) and the Canadian Crohn's and Colitis Foundation (PB). PB, DM and TA are supported by the Canadian Institute for Health Research and by the Alberta Heritage Foundation for Medical Research salary support programs.

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Authors and Affiliations

  1. Department of Medical Sciences, University of Calgary, Calgary, Alberta, Canada

    T Alain

  2. Division of Gastroenterology, Faculty of Medicine, Gastrointestinal Research Group and Mucosal Inflammation Research Group, University of Calgary, Calgary, Alberta, Canada

    J F Wong, R Endersby & P L Beck

  3. Department of Pathology, University of Calgary, Calgary, Alberta, Canada

    S J Urbanski

  4. Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada

    P W Lee

  5. Department of Medicine, University of Calgary, Calgary, Alberta, Canada

    D A Muruve, P A Forsyth & P L Beck

  6. Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada

    R N Johnston & P A Forsyth

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  1. T Alain
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  2. J F Wong
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  3. R Endersby
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  8. P A Forsyth
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  9. P L Beck
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Corresponding author

Correspondence to P L Beck.

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Alain, T., Wong, J., Endersby, R. et al. Reovirus decreases azoxymethane-induced aberrant crypt foci and colon cancer in a rodent model. Cancer Gene Ther 14, 867–872 (2007). https://doi.org/10.1038/sj.cgt.7701068

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  • DOI: https://doi.org/10.1038/sj.cgt.7701068

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