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Reduced Glioma Growth Following Dexamethasone or Anti-Angiopoietin 2 Treatment.

Posted on: 03/30/2008

Brain Pathol. 2008 Mar 26; [Epub ahead of print]

Reduced Glioma Growth Following Dexamethasone or Anti-Angiopoietin 2 Treatment.

Villeneuve J, Galarneau H, Beaudet MJ, Tremblay P, Chernomoretz A, Vallieres L.

Department of Oncology and Molecular Endocrinology, Laval University Hospital Research Center, Quebec City, Quebec, Canada.

All patients with glioblastoma, the most aggressive and common form of brain cancer, develop cerebral edema. This complication is routinely treated with dexamethasone, a steroidal anti-inflammatory drug whose effects on brain tumors are not fully understood. Here we show that dexamethasone can reduce glioma growth in mice, even though it depletes infiltrating T cells with potential antitumor activity. More precisely, T cells with helper or cytotoxic function were sensitive to dexamethasone, but not those that were negative for the CD4 and CD8 molecules, including gammadelta and natural killer (NK) T cells. The antineoplastic effect of dexamethasone was indirect, as it did not meaningfully affect the growth and gene expression profile of glioma cells in vitro. In contrast, hundreds of dexamethasone-modulated genes, notably angiopoietin 2 (Angpt2), were identified in cultured cerebral endothelial cells by microarray analysis. The ability of dexamethasone to attenuate Angpt2 expression was confirmed in vitro and in vivo. Selective neutralization of Angpt2 using a peptide-Fc fusion protein reduced glioma growth and vascular enlargement to a greater extent than dexamethasone, without affecting T cell infiltration. In conclusion, this study suggests a mechanism by which dexamethasone can slow glioma growth, providing a new therapeutic target for malignant brain tumors.

PMID: 18371178 [PubMed - as supplied by publisher]

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