MURAGAKI Yoshihiro    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Visiting Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Bevacizumab changes vascular structure and modulates the expression of angiogenic factors in recurrent malignant gliomas
Journal	Formal name：Brain Tumor Pathol ISSN code：1861387X (Electronic)14337398 (Linking)
Volume, Issue, Page	33(2),pp.129-136
Author and coauthor	OKAMOTO Saori†, NITTA Masayuki, MARUYAMA Takashi, SAWADA Tatsuo, KOMORI Takashi, OKADA Yoshikazu, MURAGAKI Yoshihiro
Publication date	2016/04
Summary	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.
DOI	10.1007/s10014-016-0248-6
Document No.	26826105