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Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy.


ABSTRACT: 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.

SUBMITTER: Mangala LS 

PROVIDER: S-EPMC5070952 | biostudies-other | 2016 Oct

REPOSITORIES: biostudies-other

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Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy.

Mangala Lingegowda S LS   Wang Hongyu H   Jiang Dahai D   Wu Sherry Y SY   Somasunderam Anoma A   Volk David E DE   Lokesh Ganesh L R GLR   Li Xin X   Pradeep Sunila S   Yang Xianbin X   Haemmerle Monika M   Rodriguez-Aguayo Cristian C   Nagaraja Archana S AS   Rupaimoole Rajesha R   Bayraktar Emine E   Bayraktar Recep R   Li Li L   Tanaka Takemi T   Hu Wei W   Ivan Cristina C   Gharpure Kshipra M KM   McGuire Michael H MH   Thiviyanathan Varatharasa V   Zhang Xinna X   Maiti Sourindra N SN   Bulayeva Nataliya N   Choi Hyun-Jin HJ   Dorniak Piotr L PL   Cooper Laurence Jn LJ   Rosenblatt Kevin P KP   Lopez-Berestein Gabriel G   Gorenstein David G DG   Sood Anil K AK  

JCI insight 20161020 17


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 mi  ...[more]

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