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01-04-2016 | Original Article

Bevacizumab changes vascular structure and modulates the expression of angiogenic factors in recurrent malignant gliomas

Authors: Saori Okamoto, Masayuki Nitta, Takashi Maruyama, Tatsuo Sawada, Takashi Komori, Yoshikazu Okada, Yoshihiro Muragaki

Published in: Brain Tumor Pathology | Issue 2/2016

Abstract

Bevacizumab (BV), a monoclonal antibody against vascular endothelial growth factor (VEGF), is currently used in the treatment of malignant glioma. To understand mechanisms of resistance to BV, we investigated morphological changes in tumor vessels and expression of angiogenic factors, such as VEGF, Flt-1, basic fibroblast growth factor (bFGF), and platelet-derived growth factor-BB (PDGF-BB), in four autopsied tumors after BV treatment. Three patients had glioblastomas; the fourth had a secondary glioblastoma that developed from a diffuse astrocytoma. BV was administered because of recurrence following the use of the Stupp regimen in these four patients. We compared the initial surgical specimen with that obtained after death following BV treatment. Immunohistochemical staining of the autopsied tumors showed that Flt-1 expression increased while VEGF expression was significantly reduced. Additionally, other angiogenic factors, particularly bFGF, were enhanced. Interestingly, the proliferation of endothelial cells was reduced, but remarkable proliferation of pericytes was observed. These results suggest that following BV treatment, glioblastomas can grow tumor vessels by expressing various angiogenic factors. These mechanisms might be important for rapid regrowth and blood brain barrier repair after BV treatment. Inhibition of multiple angiogenic factors will be required to control tumor vessels in glioblastoma.

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Title: Bevacizumab changes vascular structure and modulates the expression of angiogenic factors in recurrent malignant gliomas
Authors: Saori Okamoto
Masayuki Nitta
Takashi Maruyama
Tatsuo Sawada
Takashi Komori
Yoshikazu Okada
Yoshihiro Muragaki
Publication date: 01-04-2016
Publisher: Springer Japan
Published in: Brain Tumor Pathology / Issue 2/2016
Print ISSN: 1433-7398
Electronic ISSN: 1861-387X
DOI: https://doi.org/10.1007/s10014-016-0248-6

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Bevacizumab changes vascular structure and modulates the expression of angiogenic factors in recurrent malignant gliomas

Abstract

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Abstract

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