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Specific Inhibition of DNMT3A/ISGF3γ Interaction Increases the Temozolomide Efficiency to Reduce Tumor Growth

DNA methylation is a fundamental feature of genomes and is a candidate for pharmacological manipulation that might have important therapeutic advantage. Thus, DNA methyltransferases (DNMTs) appear to be ideal targets for drug intervention. By focusing on interactions existing between DNMT3A and DNMT...

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Autores principales: Cheray, Mathilde, Pacaud, Romain, Nadaradjane, Arulraj, Oliver, Lisa, Vallette, François M, Cartron, Pierre-François
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039338/
https://www.ncbi.nlm.nih.gov/pubmed/27698935
http://dx.doi.org/10.7150/thno.9150
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author Cheray, Mathilde
Pacaud, Romain
Nadaradjane, Arulraj
Oliver, Lisa
Vallette, François M
Cartron, Pierre-François
author_facet Cheray, Mathilde
Pacaud, Romain
Nadaradjane, Arulraj
Oliver, Lisa
Vallette, François M
Cartron, Pierre-François
author_sort Cheray, Mathilde
collection PubMed
description DNA methylation is a fundamental feature of genomes and is a candidate for pharmacological manipulation that might have important therapeutic advantage. Thus, DNA methyltransferases (DNMTs) appear to be ideal targets for drug intervention. By focusing on interactions existing between DNMT3A and DNMT3A-binding protein (D3A-BP), our work identifies the DNMT3A/ISGF3γ interaction such as a biomarker whose the presence level is associated with a poor survival prognosis and with a poor prognosis of response to the conventional chemotherapeutic treatment of glioblastoma multiforme (radiation plus temozolomide). Our data also demonstrates that the disruption of DNMT3A/ISGF3γ interactions increases the efficiency of chemotherapeutic treatment on established tumors in mice. Thus, our data opens a promising and innovative alternative to the development of specific DNMT inhibitors.
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spelling pubmed-50393382016-10-03 Specific Inhibition of DNMT3A/ISGF3γ Interaction Increases the Temozolomide Efficiency to Reduce Tumor Growth Cheray, Mathilde Pacaud, Romain Nadaradjane, Arulraj Oliver, Lisa Vallette, François M Cartron, Pierre-François Theranostics Research Paper DNA methylation is a fundamental feature of genomes and is a candidate for pharmacological manipulation that might have important therapeutic advantage. Thus, DNA methyltransferases (DNMTs) appear to be ideal targets for drug intervention. By focusing on interactions existing between DNMT3A and DNMT3A-binding protein (D3A-BP), our work identifies the DNMT3A/ISGF3γ interaction such as a biomarker whose the presence level is associated with a poor survival prognosis and with a poor prognosis of response to the conventional chemotherapeutic treatment of glioblastoma multiforme (radiation plus temozolomide). Our data also demonstrates that the disruption of DNMT3A/ISGF3γ interactions increases the efficiency of chemotherapeutic treatment on established tumors in mice. Thus, our data opens a promising and innovative alternative to the development of specific DNMT inhibitors. Ivyspring International Publisher 2016-08-25 /pmc/articles/PMC5039338/ /pubmed/27698935 http://dx.doi.org/10.7150/thno.9150 Text en © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
spellingShingle Research Paper
Cheray, Mathilde
Pacaud, Romain
Nadaradjane, Arulraj
Oliver, Lisa
Vallette, François M
Cartron, Pierre-François
Specific Inhibition of DNMT3A/ISGF3γ Interaction Increases the Temozolomide Efficiency to Reduce Tumor Growth
title Specific Inhibition of DNMT3A/ISGF3γ Interaction Increases the Temozolomide Efficiency to Reduce Tumor Growth
title_full Specific Inhibition of DNMT3A/ISGF3γ Interaction Increases the Temozolomide Efficiency to Reduce Tumor Growth
title_fullStr Specific Inhibition of DNMT3A/ISGF3γ Interaction Increases the Temozolomide Efficiency to Reduce Tumor Growth
title_full_unstemmed Specific Inhibition of DNMT3A/ISGF3γ Interaction Increases the Temozolomide Efficiency to Reduce Tumor Growth
title_short Specific Inhibition of DNMT3A/ISGF3γ Interaction Increases the Temozolomide Efficiency to Reduce Tumor Growth
title_sort specific inhibition of dnmt3a/isgf3γ interaction increases the temozolomide efficiency to reduce tumor growth
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039338/
https://www.ncbi.nlm.nih.gov/pubmed/27698935
http://dx.doi.org/10.7150/thno.9150
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