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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Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10156305_v18_n3_p401_Villeneuve http://hdl.handle.net/20.500.12110/paper_10156305_v18_n3_p401_Villeneuve |
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paper:paper_10156305_v18_n3_p401_Villeneuve2023-06-08T15:59:46Z Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment Chernomoretz, Ariel 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 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. Fil:Chernomoretz, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2008 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10156305_v18_n3_p401_Villeneuve http://hdl.handle.net/20.500.12110/paper_10156305_v18_n3_p401_Villeneuve |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
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 |
spellingShingle |
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 Chernomoretz, Ariel Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment |
topic_facet |
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 |
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. |
author |
Chernomoretz, Ariel |
author_facet |
Chernomoretz, Ariel |
author_sort |
Chernomoretz, Ariel |
title |
Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment |
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 |
publishDate |
2008 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10156305_v18_n3_p401_Villeneuve http://hdl.handle.net/20.500.12110/paper_10156305_v18_n3_p401_Villeneuve |
work_keys_str_mv |
AT chernomoretzariel reducedgliomagrowthfollowingdexamethasoneorantiangiopoietin2treatment |
_version_ |
1768542466938503168 |