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Intra-arterial delivery of endostatin gene to brain tumors prolongs survival and alters tumor vessel ultrastructure

Gene Therapy volume 11, pages 1283–1289 (2004)Cite this article

Abstract

Glioblastoma multiforme (GBM) is an incurable malignant brain tumor, usually fatal within 1 year of diagnosis. Using a syngeneic rat 9L gliosarcoma model, we have developed a novel drug delivery method in which naked plasmid DNA is selectively targeted to brain tumors via intra-arterial injection. Using a plasmid encoding the antiangiogenic endostatin, transgene expression can be detected in tumor cells in vivo, and therapeutic efficacy is observed. Administration of this plasmid resulted in an 80% tumor volume reduction 1 week after treatment and enhanced survival time by up to 47%. Treated tumors exhibited a 40% decrease in the number of tumor vessels; ultrastructural analysis of remaining tumor vessels demonstrated a number of changes including markedly narrowed or collapsed lumens. We conclude that intra-arterial injection of plasmids selectively targets therapeutic genes to CNS neoplasms. This method of gene therapy holds promise for the treatment of these highly malignant brain tumors.

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Acknowledgements

This work was supported by grants to MF from the National Eye Institute R24EY14174 and the Robert Mealey Program for the Study of Macular Degenerations. FB is a Skaggs Scholar in Clinical Science and receives grant support from the Skaggs Program. We are grateful to numerous members of the Friedlander Laboratory for assistance in various aspects of this project and to the staff and veterinarians of the LARC at TSRI for their excellent assistance.

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Authors and Affiliations

  1. Department of Cell Biology, The Scripps Research Institute, La Jolla, CA, USA

    F H Barnett, M Scharer-Schuksz, M Wood & M Friedlander

  2. The Oncology Research Institute, Greenville Hospital System, Greenville, SC, USA

    X Yu & T E Wagner

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  1. F H Barnett
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  2. M Scharer-Schuksz
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  3. M Wood
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  4. X Yu
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  5. T E Wagner
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  6. M Friedlander
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Barnett, F., Scharer-Schuksz, M., Wood, M. et al. Intra-arterial delivery of endostatin gene to brain tumors prolongs survival and alters tumor vessel ultrastructure. Gene Ther 11, 1283–1289 (2004). https://doi.org/10.1038/sj.gt.3302287

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