Development of an anti-angiogenic therapeutic model combining scAAV2-delivered siRNAs and noninvasive photoacoustic imaging of tumor vasculature development.
Development of an anti-angiogenic therapeutic model combining scAAV2-delivered siRNAs and noninvasive photoacoustic imaging of tumor vasculature development.
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DOI：
10.1016/j.canlet.2012.11.016
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发表时间：
2013-05-10
期刊：
影响因子：
9.7
通讯作者：
Cai, Jun
中科院分区：
文献类型：
--
作者：
Ruan, Qing;Xi, Lei;Boye, Sanford L.;Han, Song;Chen, Zhi J.;Hauswirth, William W.;Lewin, Alfed S.;Boulton, Michael E.;Law, Brian K.;Jiang, Wen G.;Jiang, Huabei;Cai, Jun
Preclinical studies have established tumor angiogenesis as a potential therapeutic target for breast cancer. However, there is an urgent need to either improve existing anti-angiogenic agents or devise new anti-angiogenic therapy for a subset of breast cancer patients with resistance to current anti-angiogenic regimes. The purpose of this study is to develop an anti-angiogenic therapeutic model for breast cancer by a combination of 1) siRNA-based therapy intratumorally delivered by self-complementary adeno-associated virus serotype 2 (scAAV2) vector to target tumor vasculature, and 2) non-invasive monitoring for tumor response to anti-angiogenic agents by serial photoacoustic imaging. We have reported previously that under the stress conditions caused by tumor microenvironment or/and anti-VEGF therapies, endothelial cells adopt the up-regulation of IRE1α/XBP-1 and ATF6. This in turn maintains VEGF intracrine signaling for endothelial cell survival. Here we identified that scAAV2 septuplet-Y-F mutant vector was able to transfect mice microvascular endothelial cells with high efficiency. scAAV2 septuplet-tyrosine mutant vectors encoding the siRNAs against IRE1α or XBP-1 or ATF6 significantly inhibited breast cancer-induced angiogenesis in vitro by, in part, inhibiting endothelial cell survival. Acoustic-resolution photoacoustic microscopy (ARPAM) can provide non-invasive, label-free, high resolution vascular imaging. Utilizing ARAM, we showed that intratumoral delivering the siRNAs against IRE1α or XBP-1 or ATF6 by scAAV2 septuplet-tyrosine mutant vector resulted in a significant decrease in tumor growth and tumor angiogenesis in breast cancer xenograft models. These data have generated a proof-to-concept model with important implications for the development of novel anti-angiogenic targeted therapies for patients with breast cancer.
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影响因子：
56.9
作者：
JENSEN, HM;CHEN, I;LEWIS, AE
通讯作者：
LEWIS, AE
影响因子：
4.4
作者：
Cai, Jun;Kehoe, Oksana;Boulton, Michael E.
通讯作者：
Boulton, Michael E.
DOI：
10.1073/pnas.032652399
发表时间：
2002-02-05
影响因子：
11.1
作者：
Paddison, PJ;Caudy, AA;Hannon, GJ
通讯作者：
Hannon, GJ
影响因子：
4.8
作者：
Cai, J;Jiang, WG;Boulton, M
通讯作者：
Boulton, M
影响因子：
11.2
作者：
Jiang, Chen Chen;Chen, Li Hua;Hersey, Peter
通讯作者：
Hersey, Peter