Abstract:
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. © 2008 The Authors.
Registro:
Documento: |
Artículo
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Título: | Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment |
Autor: | Villeneuve, J.; Galarneau, H.; Beaudet, M.-J.; Tremblay, P.; Chernomoretz, A.; Vallières, L. |
Filiación: | Departamento de Fisica, Facultad de Ciencias Exactas Y Naturales, Ciudad Universitaria, 1428 Buenos Aires, Argentina Department of Oncology and Molecular Endocrinology, Laval University Hospital Research Center, 2705 Laurier Boulevard, T3-67, Québec City, QC G1V 4G2, Canada Department of Oncology and Molecular Endocrinology, Laval University Hospital Research Center, Québec City, QC, Canada
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Palabras clave: | Angiopoietin-2; Antitumor immunity; Gene profiling; Glioblastoma; Glucocorticoid; Tumor endothelium; angiopoietin 2; dexamethasone; L1 10 antibody; protein antibody; animal cell; animal experiment; animal model; animal tissue; antineoplastic activity; article; brain edema; cachexia; cancer cell; cell infiltration; controlled study; drug dose comparison; drug effect; endothelium cell; gene expression; gene expression profiling; glioma; in vitro study; in vivo study; male; microarray analysis; mouse; muscle atrophy; natural killer T cell; nonhuman; protein expression; T lymphocyte; tumor growth; Angiopoietin-2; Animals; Anti-Inflammatory Agents; Brain Neoplasms; Dexamethasone; Flow Cytometry; Gene Expression; Glioma; Immunohistochemistry; In Situ Hybridization; Male; Mice; Mice, Inbred C57BL; Neovascularization, Pathologic; Oligonucleotide Array Sequence Analysis; Recombinant Fusion Proteins; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes |
Año: | 2008
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Volumen: | 18
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Número: | 3
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Página de inicio: | 401
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Página de fin: | 414
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DOI: |
http://dx.doi.org/10.1111/j.1750-3639.2008.00139.x |
Título revista: | Brain Pathology
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Título revista abreviado: | Brain Pathol.
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ISSN: | 10156305
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CODEN: | BRPAE
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CAS: | angiopoietin 2, 194368-66-6; dexamethasone, 50-02-2; Angiopoietin-2; Anti-Inflammatory Agents; Dexamethasone, 50-02-2; Recombinant Fusion Proteins
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10156305_v18_n3_p401_Villeneuve |
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Citas:
---------- APA ----------
Villeneuve, J., Galarneau, H., Beaudet, M.-J., Tremblay, P., Chernomoretz, A. & Vallières, L.
(2008)
. Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment. Brain Pathology, 18(3), 401-414.
http://dx.doi.org/10.1111/j.1750-3639.2008.00139.x---------- CHICAGO ----------
Villeneuve, J., Galarneau, H., Beaudet, M.-J., Tremblay, P., Chernomoretz, A., Vallières, L.
"Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment"
. Brain Pathology 18, no. 3
(2008) : 401-414.
http://dx.doi.org/10.1111/j.1750-3639.2008.00139.x---------- MLA ----------
Villeneuve, J., Galarneau, H., Beaudet, M.-J., Tremblay, P., Chernomoretz, A., Vallières, L.
"Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment"
. Brain Pathology, vol. 18, no. 3, 2008, pp. 401-414.
http://dx.doi.org/10.1111/j.1750-3639.2008.00139.x---------- VANCOUVER ----------
Villeneuve, J., Galarneau, H., Beaudet, M.-J., Tremblay, P., Chernomoretz, A., Vallières, L. Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment. Brain Pathol. 2008;18(3):401-414.
http://dx.doi.org/10.1111/j.1750-3639.2008.00139.x