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The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma()

Angiopoietin 2 (Ang2) is a secreted glycoprotein upregulated at sites of angiogenesis and has been implicated in cancer neovascularization. Recent studies have suggested efficacy of combined Ang and vascular endothelial growth factor receptor (VEGFR) inhibition for patients with metastatic renal cel...

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Autores principales: Wang, Xiaoen, Bullock, Andrea J., Zhang, Liang, Wei, Lin, Yu, Dongyin, Mahagaokar, Kedar, Alsop, David C., Mier, James W., Atkins, Michael B., Coxon, Angela, Oliner, Jon, Bhatt, Rupal S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101387/
https://www.ncbi.nlm.nih.gov/pubmed/24704536
http://dx.doi.org/10.1016/j.tranon.2014.02.003
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author Wang, Xiaoen
Bullock, Andrea J.
Zhang, Liang
Wei, Lin
Yu, Dongyin
Mahagaokar, Kedar
Alsop, David C.
Mier, James W.
Atkins, Michael B.
Coxon, Angela
Oliner, Jon
Bhatt, Rupal S.
author_facet Wang, Xiaoen
Bullock, Andrea J.
Zhang, Liang
Wei, Lin
Yu, Dongyin
Mahagaokar, Kedar
Alsop, David C.
Mier, James W.
Atkins, Michael B.
Coxon, Angela
Oliner, Jon
Bhatt, Rupal S.
author_sort Wang, Xiaoen
collection PubMed
description Angiopoietin 2 (Ang2) is a secreted glycoprotein upregulated at sites of angiogenesis and has been implicated in cancer neovascularization. Recent studies have suggested efficacy of combined Ang and vascular endothelial growth factor receptor (VEGFR) inhibition for patients with metastatic renal cell carcinoma (mRCC). We measured Ang2 expression in human tissue and plasma, and tested the effect of dual Ang1/2 (trebananib; AMG386) or Ang2 alone (L1-7) inhibition with VEGFR inhibition on murine RCC growth and blood flow. Ang2 levels were higher in human tumors than normal tissues with RCC ranking highest for Ang2 expression across all tumor types tested. Plasma Ang2 was significantly higher in patients with mRCC compared to controls or patients with stage I disease. Plasma Ang2 decreased with sunitinib treatment and increased at time of disease progression. In the RCC mouse, dual Ang1/2 and Ang2 inhibition improved the activity of sunitinib. Combined Ang1/2 and VEGFR inhibition prevented the resumption of blood flow associated with sunitinib resistance. Thus, Ang2 inhibition, independent of Ang1 inhibition, improves the activity of sunitinib and plasma Ang2 increases in the setting of progression on sunitinib possibly contributing to resistance. Further, arterial spin-labeled perfusion magnetic resonance imaging might be a non-invasive marker of the antiangiogenic activity of Ang inhibitors.
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spelling pubmed-41013872014-07-24 The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma() Wang, Xiaoen Bullock, Andrea J. Zhang, Liang Wei, Lin Yu, Dongyin Mahagaokar, Kedar Alsop, David C. Mier, James W. Atkins, Michael B. Coxon, Angela Oliner, Jon Bhatt, Rupal S. Transl Oncol Article Angiopoietin 2 (Ang2) is a secreted glycoprotein upregulated at sites of angiogenesis and has been implicated in cancer neovascularization. Recent studies have suggested efficacy of combined Ang and vascular endothelial growth factor receptor (VEGFR) inhibition for patients with metastatic renal cell carcinoma (mRCC). We measured Ang2 expression in human tissue and plasma, and tested the effect of dual Ang1/2 (trebananib; AMG386) or Ang2 alone (L1-7) inhibition with VEGFR inhibition on murine RCC growth and blood flow. Ang2 levels were higher in human tumors than normal tissues with RCC ranking highest for Ang2 expression across all tumor types tested. Plasma Ang2 was significantly higher in patients with mRCC compared to controls or patients with stage I disease. Plasma Ang2 decreased with sunitinib treatment and increased at time of disease progression. In the RCC mouse, dual Ang1/2 and Ang2 inhibition improved the activity of sunitinib. Combined Ang1/2 and VEGFR inhibition prevented the resumption of blood flow associated with sunitinib resistance. Thus, Ang2 inhibition, independent of Ang1 inhibition, improves the activity of sunitinib and plasma Ang2 increases in the setting of progression on sunitinib possibly contributing to resistance. Further, arterial spin-labeled perfusion magnetic resonance imaging might be a non-invasive marker of the antiangiogenic activity of Ang inhibitors. Neoplasia Press 2014-03-04 /pmc/articles/PMC4101387/ /pubmed/24704536 http://dx.doi.org/10.1016/j.tranon.2014.02.003 Text en Copyright © 2014 Neoplasia Press, Inc. All rights reserved. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
spellingShingle Article
Wang, Xiaoen
Bullock, Andrea J.
Zhang, Liang
Wei, Lin
Yu, Dongyin
Mahagaokar, Kedar
Alsop, David C.
Mier, James W.
Atkins, Michael B.
Coxon, Angela
Oliner, Jon
Bhatt, Rupal S.
The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma()
title The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma()
title_full The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma()
title_fullStr The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma()
title_full_unstemmed The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma()
title_short The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma()
title_sort role of angiopoietins as potential therapeutic targets in renal cell carcinoma()
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101387/
https://www.ncbi.nlm.nih.gov/pubmed/24704536
http://dx.doi.org/10.1016/j.tranon.2014.02.003
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