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Radiotherapy-Associated Long-term Modification of Expression of the Inflammatory Biomarker Genes ARG1, BCL2L1, and MYC

Ionizing radiation (IR) exposure of cells in vitro and in vivo triggers a complex cellular response among which modifications of gene expression have been consistently reported. Nevertheless, little is currently known about the transcriptionally responsive genes which play a role in the inflammation...

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Autores principales: Manning, Grainne, Tichý, Aleš, Sirák, Igor, Badie, Christophe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385838/
https://www.ncbi.nlm.nih.gov/pubmed/28443095
http://dx.doi.org/10.3389/fimmu.2017.00412
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author Manning, Grainne
Tichý, Aleš
Sirák, Igor
Badie, Christophe
author_facet Manning, Grainne
Tichý, Aleš
Sirák, Igor
Badie, Christophe
author_sort Manning, Grainne
collection PubMed
description Ionizing radiation (IR) exposure of cells in vitro and in vivo triggers a complex cellular response among which modifications of gene expression have been consistently reported. Nevertheless, little is currently known about the transcriptionally responsive genes which play a role in the inflammation response. In order to improve our understanding of such transcriptional response to radiation in vivo, we simultaneously monitored the expression of 249 genes associated with the inflammation response over the course of the radiotherapy treatment in blood of patients treated for endometrial or head and neck cancer. We have identified genes whose transcriptional expression is either upregulated (ARG1, BCL2L1) or downregulated (MYC) several fold in vivo. These modifications were consistently detected across patients and further confirmed by quantitative real-time polymerase chain reaction (QRT-PCR); they were specifically significant toward the end of the radiotherapy treatment, 5 weeks following the first radiation fraction and more pronounced in endometrial patients (respectively, 2.9, 4.1, and 1.8 times). Importantly, in an attempt to correlate expression levels with normal tissue reaction to IR, we also identified three other genes CD40, OAS2, and CXCR1 whose expression level fluctuations during radiotherapy were more pronounced in patients developing late normal tissue responses to curative radiotherapy after the end of the radiotherapy treatment. Overall, we identified inflammation-associated genes which are promising biomarkers of IR exposure and susceptibility to radiation-induced toxicity.
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spelling pubmed-53858382017-04-25 Radiotherapy-Associated Long-term Modification of Expression of the Inflammatory Biomarker Genes ARG1, BCL2L1, and MYC Manning, Grainne Tichý, Aleš Sirák, Igor Badie, Christophe Front Immunol Immunology Ionizing radiation (IR) exposure of cells in vitro and in vivo triggers a complex cellular response among which modifications of gene expression have been consistently reported. Nevertheless, little is currently known about the transcriptionally responsive genes which play a role in the inflammation response. In order to improve our understanding of such transcriptional response to radiation in vivo, we simultaneously monitored the expression of 249 genes associated with the inflammation response over the course of the radiotherapy treatment in blood of patients treated for endometrial or head and neck cancer. We have identified genes whose transcriptional expression is either upregulated (ARG1, BCL2L1) or downregulated (MYC) several fold in vivo. These modifications were consistently detected across patients and further confirmed by quantitative real-time polymerase chain reaction (QRT-PCR); they were specifically significant toward the end of the radiotherapy treatment, 5 weeks following the first radiation fraction and more pronounced in endometrial patients (respectively, 2.9, 4.1, and 1.8 times). Importantly, in an attempt to correlate expression levels with normal tissue reaction to IR, we also identified three other genes CD40, OAS2, and CXCR1 whose expression level fluctuations during radiotherapy were more pronounced in patients developing late normal tissue responses to curative radiotherapy after the end of the radiotherapy treatment. Overall, we identified inflammation-associated genes which are promising biomarkers of IR exposure and susceptibility to radiation-induced toxicity. Frontiers Media S.A. 2017-04-10 /pmc/articles/PMC5385838/ /pubmed/28443095 http://dx.doi.org/10.3389/fimmu.2017.00412 Text en Copyright © 2017 Manning, Tichý, Sirák and Badie. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Manning, Grainne
Tichý, Aleš
Sirák, Igor
Badie, Christophe
Radiotherapy-Associated Long-term Modification of Expression of the Inflammatory Biomarker Genes ARG1, BCL2L1, and MYC
title Radiotherapy-Associated Long-term Modification of Expression of the Inflammatory Biomarker Genes ARG1, BCL2L1, and MYC
title_full Radiotherapy-Associated Long-term Modification of Expression of the Inflammatory Biomarker Genes ARG1, BCL2L1, and MYC
title_fullStr Radiotherapy-Associated Long-term Modification of Expression of the Inflammatory Biomarker Genes ARG1, BCL2L1, and MYC
title_full_unstemmed Radiotherapy-Associated Long-term Modification of Expression of the Inflammatory Biomarker Genes ARG1, BCL2L1, and MYC
title_short Radiotherapy-Associated Long-term Modification of Expression of the Inflammatory Biomarker Genes ARG1, BCL2L1, and MYC
title_sort radiotherapy-associated long-term modification of expression of the inflammatory biomarker genes arg1, bcl2l1, and myc
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385838/
https://www.ncbi.nlm.nih.gov/pubmed/28443095
http://dx.doi.org/10.3389/fimmu.2017.00412
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