Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment

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 reduc...

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Autores: Villeneuve, Jérôme, Galarneau, Hugo, Beaudet, Marie Josée, Tremblay, Pierrot, Chernomoretz, Ariel, Vallières, Luc
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2008
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/62173
Acceso en línea:http://hdl.handle.net/11336/62173
Access Level:acceso abierto
Palabra clave:Angiopoietin-2
Antitumor Immunity
Gene Profiling
Glioblastoma
Glucocorticoid
Tumor Endothelium
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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spelling Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatmentVilleneuve, JérômeGalarneau, HugoBeaudet, Marie JoséeTremblay, PierrotChernomoretz, ArielVallières, LucAngiopoietin-2Antitumor ImmunityGene ProfilingGlioblastomaGlucocorticoidTumor Endotheliumhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1All 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.Fil: Villeneuve, Jérôme. Laval University; CanadáFil: Galarneau, Hugo. Laval University; CanadáFil: Beaudet, Marie Josée. Laval University; CanadáFil: Tremblay, Pierrot. Laval University; CanadáFil: Chernomoretz, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Vallières, Luc. Laval University; CanadáWiley Blackwell Publishing, Inc2008-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/62173Villeneuve, Jérôme; Galarneau, Hugo; Beaudet, Marie Josée; Tremblay, Pierrot; Chernomoretz, Ariel; et al.; Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment; Wiley Blackwell Publishing, Inc; Brain Pathology; 18; 3; 7-2008; 401-4141015-6305CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1750-3639.2008.00139.xinfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1750-3639.2008.00139.xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T13:41:04Zoai:ri.conicet.gov.ar:11336/62173instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 13:41:04.404CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment
title Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment
spellingShingle Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment
Villeneuve, Jérôme
Angiopoietin-2
Antitumor Immunity
Gene Profiling
Glioblastoma
Glucocorticoid
Tumor Endothelium
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
title_short Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment
title_full Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment
title_fullStr Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment
title_full_unstemmed Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment
title_sort Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment
dc.creator.none.fl_str_mv Villeneuve, Jérôme
Galarneau, Hugo
Beaudet, Marie Josée
Tremblay, Pierrot
Chernomoretz, Ariel
Vallières, Luc
author Villeneuve, Jérôme
author_facet Villeneuve, Jérôme
Galarneau, Hugo
Beaudet, Marie Josée
Tremblay, Pierrot
Chernomoretz, Ariel
Vallières, Luc
author_role author
author2 Galarneau, Hugo
Beaudet, Marie Josée
Tremblay, Pierrot
Chernomoretz, Ariel
Vallières, Luc
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Angiopoietin-2
Antitumor Immunity
Gene Profiling
Glioblastoma
Glucocorticoid
Tumor Endothelium
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
topic Angiopoietin-2
Antitumor Immunity
Gene Profiling
Glioblastoma
Glucocorticoid
Tumor Endothelium
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
description 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.
publishDate 2008
dc.date.none.fl_str_mv 2008-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/62173
Villeneuve, Jérôme; Galarneau, Hugo; Beaudet, Marie Josée; Tremblay, Pierrot; Chernomoretz, Ariel; et al.; Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment; Wiley Blackwell Publishing, Inc; Brain Pathology; 18; 3; 7-2008; 401-414
1015-6305
CONICET Digital
CONICET
url http://hdl.handle.net/11336/62173
identifier_str_mv Villeneuve, Jérôme; Galarneau, Hugo; Beaudet, Marie Josée; Tremblay, Pierrot; Chernomoretz, Ariel; et al.; Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment; Wiley Blackwell Publishing, Inc; Brain Pathology; 18; 3; 7-2008; 401-414
1015-6305
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1750-3639.2008.00139.x
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1750-3639.2008.00139.x
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 15.812429

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