Abstract | PURPOSE: EXPERIMENTAL DESIGN: To recapitulate high levels of Ang-2 in glioblastoma patients during anti- VEGF treatment, Ang-2 was ectopically expressed in U87 glioma cells. Animal survival and tumor growth were assessed to determine the effects of Ang-2 and anti- VEGF receptor 2 (VEGFR2) treatment. We also monitored morphologic and functional vascular changes using multiphoton laser scanning microscopy and immunohistochemistry. RESULTS: Ectopic expression of Ang-2 had no effect on vascular permeability, tumor growth, or survival, although it resulted in higher vascular density, with dilated vessels and reduced mural cell coverage. On the other hand, when combined with anti-VEGFR2 treatment, Ang-2 destabilized vessels without affecting vessel regression and compromised the survival benefit of VEGFR2 inhibition by increasing vascular permeability. VEGFR2 inhibition normalized tumor vasculature whereas ectopic expression of Ang-2 diminished the beneficial effects of VEGFR2 blockade by inhibiting vessel normalization. CONCLUSION:
Cancer treatment regimens combining anti- VEGF and anti-Ang-2 agents may be an effective strategy to improve the efficacy of current anti- VEGF therapies.
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Authors | Sung-Suk Chae, Walid S Kamoun, Christian T Farrar, Nathaniel D Kirkpatrick, Elisabeth Niemeyer, Annemarie M A de Graaf, A Gregory Sorensen, Lance L Munn, Rakesh K Jain, Dai Fukumura |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 16
Issue 14
Pg. 3618-27
(Jul 15 2010)
ISSN: 1557-3265 [Electronic] United States |
PMID | 20501615
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2010 AACR. |
Chemical References |
- Angiopoietin-2
- Vascular Endothelial Growth Factor Receptor-2
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Topics |
- Angiopoietin-2
(genetics, metabolism)
- Animals
- Cell Survival
- Disease Models, Animal
- Glioma
(blood supply, therapy)
- Humans
- Immunohistochemistry
- Mice
- Neoplasm Transplantation
- Neovascularization, Pathologic
(therapy)
- Reverse Transcriptase Polymerase Chain Reaction
- Vascular Endothelial Growth Factor Receptor-2
(antagonists & inhibitors, metabolism)
- Xenograft Model Antitumor Assays
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