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Intra-arterial delivery of p53-containing adenoviral vector into experimental brain tumors

Cancer Gene Therapy volume 9, pages 228–235 (2002)Cite this article

Abstract

Human tumor xenografts established in athymic rat brains were used to determine the feasibility of intravascular delivery of tumor suppressor genes to brain tumors. Both tumor size and number were compared to characterize the effect of tumor burden on tumor transduction efficacy by a control LacZ-containing adenoviral vector. Experiments with tumors grown in vivo for either 3, 5, or 7 days demonstrated that 5-day-old tumors provided the best target for vector infection and transgene expression by this mode of administration. Intra-arterial mannitol facilitated transduction efficiency. Tumor burden did not seem to affect transduction, while tumor location appeared to be an important factor. Based on these results, intra-arterial infusion of a p53-containing adenoviral vector was carried out and resulted in significant retardation of brain tumor growth 3 days after administration. Effects at longer time points were not as significant. These findings indicate that intra-arterial administration of adenoviral vectors containing p53 is efficient and can result in changes in tumor size, but that long-term control of tumor growth may require multiple adenoviral treatments.

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Acknowledgements

This work was funded by a grant from Schering-Plough to EAC. Special thanks to Dr P Rioux for his statistical analysis of the data, and Dr W Robert Bishop for his support.

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Authors and Affiliations

  1. Molecular Neuro-Oncology Laboratories, Neurosurgery Service, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA

    Tatsuya Abe, Hiroaki Wakimoto, E Antonio Chiocca & James P Basilion

  2. Canji Inc., San Diego, California, USA

    Robert Bookstein & Daniel C Maneval

  3. Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA

    James P Basilion

  4. Department of Neurosurgery, Oita Medical University, Oita, Japan

    Tatsuya Abe

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  1. Tatsuya Abe
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  2. Hiroaki Wakimoto
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Correspondence to James P Basilion.

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Abe, T., Wakimoto, H., Bookstein, R. et al. Intra-arterial delivery of p53-containing adenoviral vector into experimental brain tumors. Cancer Gene Ther 9, 228–235 (2002). https://doi.org/10.1038/sj.cgt.7700437

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  • DOI: https://doi.org/10.1038/sj.cgt.7700437

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