Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy

被引：14

作者：

Mangala, Lingegowda S. ^{[1
,2
]}

Wang, Hongyu ^{[3
,4
]}

Jiang, Dahai ^{[1
,2
]}

Wu, Sherry Y. ^{[1
]}

Somasunderam, Anoma ^{[5
]}

Volk, David E. ^{[3
,4
]}

Lokesh, Ganesh L. R. ^{[3
]}

Li, Xin ^{[3
]}

Pradeep, Sunila ^{[1
]}

Yang, Xianbin ^{[6
]}

Haemmerle, Monika ^{[1
]}

Rodriguez-Aguayo, Cristian ^{[2
,7
]}

Nagaraja, Archana S. ^{[1
]}

Rupaimoole, Rajesha ^{[1
]}

Bayraktar, Emine ^{[7
]}

Bayraktar, Recep ^{[7
]}

Li, Li ^{[3
]}

Tanaka, Takemi ^{[8
]}

Hu, Wei ^{[1
]}

Ivan, Cristina ^{[1
]}

Gharpure, Kshipra M. ^{[1
]}

McGuire, Michael H. ^{[1
]}

Thiviyanathan, Varatharasa ^{[3
,4
]}

Zhang, Xinna ^{[1
,2
]}

Maiti, Sourindra N. ^{[9
]}

Bulayeva, Nataliya ^{[3
]}

Choi, Hyun-Jin ^{[1
]}

Dorniak, Piotr L. ^{[1
]}

Cooper, Laurence J. N. ^{[9
]}

Rosenblatt, Kevin P. ^{[10
]}

Lopez-Berestein, Gabriel ^{[2
,7
,11
]}

Gorenstein, David G. ^{[3
,4
,6
]}

Sood, Anil K. ^{[1
,2
,11
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Unit 1362,POB 301439, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNAs, Unit 1362,POB 301439, Houston, TX 77030 USA

[3] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA

[4] Univ Texas Hlth Sci Ctr Houston, Dept Nanomed & Biomed Engn, Houston, TX 77030 USA

[5] Univ Texas Med Branch, Dept Internal Med, Galveston, TX 77555 USA

[6] AM Biotechnol, Houston, TX USA

[7] Univ Texas MD Anderson Canc Ctr, Expt Therapeut, Unit 1362,POB 301439, Houston, TX 77030 USA

[8] Univ Oklahoma, Hlth Sci Ctr, Biomed Res Ctr, Oklahoma City, OK USA

[9] Univ Texas MD Anderson Canc Ctr, Dept Pediat, Unit 1362,POB 301439, Houston, TX 77030 USA

[10] Compan DX Reference Lab, Houston, TX USA

[11] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Unit 1362,POB 301439, Houston, TX 77030 USA

来源：

JCI INSIGHT | 2016年 / 1卷 / 17期

关键词：

PHASE-II TRIAL; NEOADJUVANT CHEMOTHERAPY; TUMOR ANGIOGENESIS; MEMBRANE ANTIGEN; PROSTATE-CANCER; BREAST-CANCER; BEVACIZUMAB; EXPERIENCE; THERAPY; APTAMER;

D O I：

10.1172/jci.insight.87754

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Current antiangiogenesis therapy relies on inhibiting newly developed immature tumor blood vessels and starving tumor cells. This strategy has shown transient and modest efficacy. Here, we report a better approach to target cancer-associated endothelial cells (ECs), reverse permeability and leakiness of tumor blood vessels, and improve delivery of chemotherapeutic agents to the tumor. First, we identified deregulated microRNAs (miRs) from patient-derived cancer-associated ECs. Silencing these miRs led to decreased vascular permeability and increased maturation of blood vessels. Next, we screened a thioaptamer (TA) library to identify TAs selective for tumor-associated ECs. An annexin A2-targeted TA was identified and used for delivery of miR106b-5p and miR30c-5p inhibitors, resulting in vascular maturation and antitumor effects without inducing hypoxia. These findings could have implications for improving vascular-targeted therapy.

引用

页数：14

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