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A novel combination of suicide gene therapy and histone deacetylase inhibitor for treatment of malignant melanoma

Cancer Gene Therapy volume 10, pages 179–186 (2003)Cite this article

Abstract

One major problem associated with application of gene therapy to treatment of tumors is poor transgene expression. Although suicide gene therapy with the herpes simplex virus-thymidine kinase gene (HSV-tk) followed by administration of ganciclovir (GCV) was effective in the treatment of melanoma, it was still difficult to induce complete remission to cancer. A novel histone deacetylase inhibitor drug FR901229 was found to enhance transgene expression in tumor cells both in vitro and in vivo. Combination therapy with HSV-tklGCV and FR901228 by direct injection into tumor enhanced antimelanoma effects. The number of apoptotic cells in melanoma tumors was increased significantly (P<.05) after combined suicide gene therapy and FR901228. Six times injection of HSV-tk/GCV and FR901228 prolonged mice survival compared to that of HSV-tk/GCV injection alone (P=.021). In total, 56% (10 of 18) of the mice survived 120 days after combined suicide gene therapy and FR901228 treatment, and no new tumors appeared in the surviving mice. However, only 19% (3 of 16) of the mice survived when treated with suicide gene therapy alone. This novel strategy may be applicable as a therapeutic regimen for the treatment of aggressive types of cancers.

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Acknowledgements

We thank Rie Kosai for their excellent technical assistance. This work was supported by Grant 13218069 from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Seiji Yamamoto, Tomoki Yamano, Ryuichi Morishita & Yasufumi Kaneda

  2. First Department of Surgery, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan

    Seiji Yamamoto, Sonshin Takao & Takashi Aikou

  3. Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, 90404, California, USA

    Tomoki Yamano, Maki Tanaka & Dave S B Hoon

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  1. Seiji Yamamoto
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Correspondence to Yasufumi Kaneda.

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Yamamoto, S., Yamano, T., Tanaka, M. et al. A novel combination of suicide gene therapy and histone deacetylase inhibitor for treatment of malignant melanoma. Cancer Gene Ther 10, 179–186 (2003). https://doi.org/10.1038/sj.cgt.7700551

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