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Efficient and cancer-selective gene transfer to hepatocellular carcinoma in a rat using adenovirus vector with iodized oil esters

Cancer Gene Therapy volume 8, pages 713–718 (2001)Cite this article

Abstract

Gene therapy for cancer requires efficient, selective gene transfer to cancer cells. In gene therapy for hepatocellular carcinoma (HCC), gene transfer is efficient for small tumors, but not for large tumors. The delivery of anticancer agents and of iodized oil esters as embolic agents through tumor-feeding arteries is known as transarterial embolization. We speculate that genes may be efficiently and selectively transferred for HCC using iodized oil esters because these esters may remain together with a genetic vector within HCC selectively. Hence, we have studied the effect of iodized oil esters on adenovirus vector–mediated gene transfer for HCC in vivo. A rat model of HCC induced with diethylnitrosamine and phenobarbital was injected with either AxCALacZ, which expresses the β-galactosidase of Escherichia coli , or AxCALacZ and iodized oil esters into the hepatic artery. Histological comparisons revealed that the β-galactosidase expression in the rats with HCC injected with AxCALacZ and iodized oil esters was greater ( P <.0001) in small tumors ( P =.0046) and large tumors ( P =.0023), and more selective ( P =.0229) than in only AxCALacZ-injected rats. These results suggest that iodized oil esters are injected into hepatic artery together with adenovirus vector, and that genes may be efficiently and cancer-selectively transferred to HCC. Cancer Gene Therapy (2001) 8, 713–718

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Acknowledgements

We thank Dr. Saito and Dr. Kanegae (Institute of Medical Science, University of Tokyo) for providing the adenovirus vector, Dr. Miyazaki (Institute of Nutrition and Physiological Chemistry, Osaka University Graduate School of Medicine) for providing CAG promoter, the Laboratory Animal Facilities in the Jikei University School of Medicine for animal maintenance, and Teruaki Aoki for his contributions during manuscript preparation.

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Authors and Affiliations

  1. Department of Surgery, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan

    Hiroaki Shiba, Tomoyoshi Okamoto & Yasuro Futagawa

  2. Department of Gene Therapy, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan

    Hiroaki Shiba, Toya Ohashi & Yoshikatsu Eto

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  1. Hiroaki Shiba
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  2. Tomoyoshi Okamoto
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  3. Yasuro Futagawa
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  4. Toya Ohashi
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  5. Yoshikatsu Eto
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Correspondence to Hiroaki Shiba.

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Shiba, H., Okamoto, T., Futagawa, Y. et al. Efficient and cancer-selective gene transfer to hepatocellular carcinoma in a rat using adenovirus vector with iodized oil esters. Cancer Gene Ther 8, 713–718 (2001). https://doi.org/10.1038/sj.cgt.7700368

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