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Systemic gene therapy with anti-angiogenic factors inhibits spontaneous breast tumor growth and metastasis in MMTVneu transgenic mice

Abstract

Tumor growth and metastasis are angiogenesis-dependent. The possibility of inhibiting tumor growth by interfering with the formation of new vessels has recently raised considerable interest. We previously reported that it is possible to inhibit primary tumor growth and metastasis in a transgenic model of spontaneous breast tumor, which shows many similarities to its human counterpart (including ability to metastasize) by intratumoral administration of a DNA construct carrying the murine angiostatin cDNA driven by liposomes. Here we report that it is also possible to achieve this goal by a systemic (intraperitoneal) delivery of therapeutic DNA constructs carrying genes coding for mouse and human anti-angiogenic factors which include angiostatin, endostatin and TIMP-2. These findings may be relevant to the design of therapeutic interventions in humans.

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Acknowledgements

The technical assistance of Massimo Littardi and Lucia Susani is acknowledged. We thank Professor R Dulbecco and Professor L Rossi Bernardi for encouragement. The financial support of AIRC to AV and PF Biotecnologie to PV is gratefully acknowledged. This is manuscript No. 46 of the Genoma 2000/ITBA Project funded by CARIPLO.

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Sacco, M., Catò, E., Ceruti, R. et al. Systemic gene therapy with anti-angiogenic factors inhibits spontaneous breast tumor growth and metastasis in MMTVneu transgenic mice. Gene Ther 8, 67–70 (2001). https://doi.org/10.1038/sj.gt.3301358

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  • DOI: https://doi.org/10.1038/sj.gt.3301358

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