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Cancer Lett. 2013 May 10;332(1):120-9. doi: 10.1016/j.canlet.2012.11.016. Epub 2012 Nov 27.

Development of an anti-angiogenic therapeutic model combining scAAV2-delivered siRNAs and noninvasive photoacoustic imaging of tumor vasculature development.

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  • 1Department of Anatomy & Cell Biology, University of Florida, Gainesville, FL 32610, USA.

Abstract

We aimed to develop an anti-angiogenic model for breast cancer by combining (1) siRNA-based therapy delivered by self-complementary adeno-associated virus serotype 2 (scAAV2) vectors to target tumor vasculature, and (2) noninvasive monitoring to tumor response to anti-angiogenesis by photoacoustic (PA) imaging. scAAV2 vector containing 7 surface exposed tyrosine to phenylanine capsid mutations was able to transduce microvascular endothelial cells with high efficiency. siRNAs against UPR (unfolded protein response)-IRE1α, XBP-1, ATF6 significantly inhibited breast cancer-induced angiogenesis in vitro by inhibiting endothelial cell survival. PA imaging showed that knockdown of UPR proteins greatly reduced tumor angiogenesis in vivo in breast cancer models.

Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

PMID:
23196055
[PubMed - indexed for MEDLINE]
PMCID:
PMC4094357
Free PMC Article
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