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This Article Full Text Full Text (PDF) All Versions of this Article: 11/5/488    most recent 15228517-2008-117v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Valable, S. Articles by Petit, E. Search for Related Content PubMed PubMed Citation Social Bookmarking                   What's this?

MRI assessment of hemodynamic effects of angiopoietin-2 overexpression in a brain tumor model

UMR 6232, CI-NAPS, CERVOxy Group, Centre CYCERON, Caen (S.V., D.E., J.-M.C., J.-S.G., M.B., S.R., E.P.); Unité IRM Pôle Imagerie (J.-M.C.) and Department of Neurology (J.-S.G.), Centre Hospitalier Universitaire Côte de Nacre; Caen, France

Address correspondence to Samuel Valable, UMR-CNRS 6232 CI-NAPS, CERVOxy Group, Centre CYCERON, Bd Henri Becquerel, BP5229, 14074 Caen CEDEX, France (valable{at}cyceron.fr).

Despite treatment efforts, the median survival in patients with glioblastoma multiforme, the most aggressive form of glioma, does not extend beyond 12–15 months. One of the major pathophysiological characteristics of these tumors is their ability to induce active angiogenesis. Thus, based on the lack of efficient therapies, agents that inhibit angiogenesis are particularly attractive as a therapeutic option. However, it has been recently proposed that although specifically targeting vascular endothelial growth factor, the main angiogenic factor, certainly leads to significant tumor regression, it could also be followed by tumor relapses. In this case, angiogenesis is driven by alternate pathways that include other angiogenic factors. One possible strategy to overcome this therapeutic obstacle is to overexpress antivascular factors such as angiopoietin-2 (Ang2). Here, by using MRI and histological analysis, we studied the vascular events involved in glioma growth impairment induced by Ang2 overexpression. Our results show that an increase in Ang2 expression, during the tumor growth, leads to a significant decrease in tumor growth (86%) along with an increase in the survival median (70%) but does not modify the tumor vascular area or cerebral blood volume. However, tumor Ang2-derived blood vessels display an abnormal, enlarged morphology. We show that the presence of Ang2 leads to an enhancement of tumor perfusion and a decrease in tumor vessel permeability. Based on our MR image evaluations of hemodynamic tumor vessel changes, we propose that Ang2-derived tumor vessels lead to an inadequate oxygenation of the tumor tissue, leading to impairment in tumor growth.

Key Words: angiogenesis • angiopoietin-2 • cerebral blood volume • glioma • MRI

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