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Expression of Concern Free access | 10.1172/jci.insight.122387

Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy

Lingegowda S. Mangala, Hongyu Wang, Dahai Jiang, Sherry Y. Wu, Anoma Somasunderam, David E. Volk, Ganesh L. R. Lokesh, Xin Li, Sunila Pradeep, Xianbin Yang, Monika Haemmerle, Cristian Rodriguez-Aguayo, Archana S Nagaraja, Rajesha Rupaimoole, Emine Bayraktar, Recep Bayraktar, Li Li, Takemi Tanaka, Wei Hu, Cristina Ivan, Kshipra M Gharpure, Michael H. McGuire, Varatharasa Thiviyanathan, Xinna Zhang, Sourindra N. Maiti, Nataliya Bulayeva, Hyun-Jin Choi, Piotr L. Dorniak, Laurence J.N. Cooper, Kevin P. Rosenblatt, Gabriel Lopez-Berestein, David G. Gorenstein, and Anil K. Sood

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Published May 29, 2018 - More info

Published in Volume 3, Issue 11 on June 7, 2018
JCI Insight. 2018;3(11):e122387. https://doi.org/10.1172/jci.insight.122387.
Copyright © 2018, American Society for Clinical Investigation
Published May 29, 2018 - Version history
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Related article:

Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy
Lingegowda S. Mangala, … , David G. Gorenstein, Anil K. Sood
Lingegowda S. Mangala, … , David G. Gorenstein, Anil K. Sood
Chitosan-thioaptamer nanoparticles deliver miRNA-inhibitors selectively to the tumor vasculature, restore tight junction function, improve the delivery of paclitaxel, and reduce tumor growth.
Research Article Angiogenesis Oncology

Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy

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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.

Authors

Lingegowda S. Mangala, Hongyu Wang, Dahai Jiang, Sherry Y. Wu, Anoma Somasunderam, David E. Volk, Ganesh L. R. Lokesh, Xin Li, Sunila Pradeep, Xianbin Yang, Monika Haemmerle, Cristian Rodriguez-Aguayo, Archana S Nagaraja, Rajesha Rupaimoole, Emine Bayraktar, Recep Bayraktar, Li Li, Takemi Tanaka, Wei Hu, Cristina Ivan, Kshipra M Gharpure, Michael H. McGuire, Varatharasa Thiviyanathan, Xinna Zhang, Sourindra N. Maiti, Nataliya Bulayeva, Hyun-Jin Choi, Piotr L. Dorniak, Laurence J.N. Cooper, Kevin P. Rosenblatt, Gabriel Lopez-Berestein, David G. Gorenstein, Anil K. Sood

×

Original citation: JCI Insight. 2016;1(17):e87754. https://doi.org/10.1172/jci.insight.87754

Citation for this expression of concern: JCI Insight. 2018;3(11):e122387. https://doi.org/10.1172/jci.insight.122387

The Editors recently became aware that the Endo40 and Endo42 samples in Supplemental Figure 4B appear to be similar. Additionally, in Supplemental Figure 9, the CH and CH/Endo28-NPs for the heart tissue appear to be the same. The Editorial Board is pursuing further investigation of this matter, and we will inform our readers of the outcome when the investigation is complete.

Footnotes

See the related article at Improving vascular maturation using noncoding RNAs increases antitumor effect of chemotherapy.

Version history
  • Version 1 (May 29, 2018): Electronic publication
  • Version 2 (June 7, 2018): Issue version

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