Universität zu Köln

von Baumgarten, Louisa, Brucker, David, Tirniceru, Anca, Kienast, Yvonne, Grau, Stefan, Burgold, Steffen, Herms, Jochen and Winkler, Frank ORCID: 0000-0003-4892-6104 (2011). Bevacizumab Has Differential and Dose-Dependent Effects on Glioma Blood Vessels and Tumor Cells. Clin. Cancer Res., 17 (19). S. 6192 - 6206. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1078-0432

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Abstract

Purpose: Bevacizumab targets VEGF-A and has proved beneficial in glioma patients, improving clinical symptoms by the reduction of tumor edema. However, it remains controversial whether or not bevacizumab exerts antitumor effects in addition to (and potentially independent of) its effects on tumor vessels, and it is unknown what doses are needed to achieve this. Experimental Design: We established a novel orthotopic glioma mouse model that allowed us to simultaneously study the kinetics of the morphologic and functional vascular changes, tumor growth, and the viability of individual tumor cells during the course of anti-VEGF therapy in the same microscopic tumor region in real-time. Three doses of bevacizumab were compared, a subclinical dose and two clinical doses (medium and high). Results: Low (subclinical) doses of bevacizumab led to a significant reduction of the total vascular volume without affecting tumor cell viability or the overall tumor growth rates. Medium and high doses triggered a similar degree of vascular regression but significantly decreased tumor growth and prolonged survival. Remaining vessels revealed morphologic features of vascular normalization, reduced permeability, and an increase in blood flow velocity; the latter was dose dependent. We observed an uncoupling of the antitumoral and the antivascular effects of bevacizumab with the high dose only, which showed the potential to cause microregional glioma cell regression. In some tumor regions, pronounced glioma cell regression occurred even without vascular regression. In vitro, there was no effect of bevacizumab on glioma cell proliferation. Conclusions: Regression of glioma cells can occur independently from vascular regression, suggesting that high doses of bevacizumab have indirect anticancer cell properties in vivo. Clin Cancer Res; 17(19); 6192-205. (C) 2011 AACR.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code von Baumgarten, Louisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Brucker, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Tirniceru, Anca UNSPECIFIED UNSPECIFIED UNSPECIFIED Kienast, Yvonne UNSPECIFIED UNSPECIFIED UNSPECIFIED Grau, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Burgold, Steffen UNSPECIFIED UNSPECIFIED UNSPECIFIED Herms, Jochen UNSPECIFIED UNSPECIFIED UNSPECIFIED Winkler, Frank UNSPECIFIED orcid.org/0000-0003-4892-6104 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-488083
DOI:	10.1158/1078-0432.CCR-10-1868
Journal or Publication Title:	Clin. Cancer Res.
Volume:	17
Number:	19
Page Range:	S. 6192 - 6206
Date:	2011
Publisher:	AMER ASSOC CANCER RESEARCH
Place of Publication:	PHILADELPHIA
ISSN:	1078-0432
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL GROWTH-FACTOR; PHASE-II TRIAL; RECURRENT GLIOBLASTOMA-MULTIFORME; SINGLE-AGENT BEVACIZUMAB; IN-VIVO; MALIGNANT GLIOMAS; ANTIANGIOGENIC THERAPY; MONOCLONAL-ANTIBODY; PROLONGS SURVIVAL; KINASE INHIBITOR Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48808