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Type 1 IGF receptor associates with adverse outcome and cellular radioresistance in paediatric high-grade glioma

High-grade glioma (HGG) is highly resistant to therapy, prompting us to investigate the contribution of insulin-like growth factor receptor (IGF-1R), linked with radioresistance in other cancers. IGF-1R immunohistochemistry in 305 adult HGG (aHGG) and 103 paediatric/young adult HGG (pHGG) cases reve...

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Autores principales: Simpson, Aaron D., Soo, Ying Wei Jenetta, Rieunier, Guillaume, Aleksic, Tamara, Ansorge, Olaf, Jones, Chris, Macaulay, Valentine M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054265/
https://www.ncbi.nlm.nih.gov/pubmed/31857716
http://dx.doi.org/10.1038/s41416-019-0677-1
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author Simpson, Aaron D.
Soo, Ying Wei Jenetta
Rieunier, Guillaume
Aleksic, Tamara
Ansorge, Olaf
Jones, Chris
Macaulay, Valentine M.
author_facet Simpson, Aaron D.
Soo, Ying Wei Jenetta
Rieunier, Guillaume
Aleksic, Tamara
Ansorge, Olaf
Jones, Chris
Macaulay, Valentine M.
author_sort Simpson, Aaron D.
collection PubMed
description High-grade glioma (HGG) is highly resistant to therapy, prompting us to investigate the contribution of insulin-like growth factor receptor (IGF-1R), linked with radioresistance in other cancers. IGF-1R immunohistochemistry in 305 adult HGG (aHGG) and 103 paediatric/young adult HGG (pHGG) cases revealed significant association with adverse survival in pHGG, with median survival of 13.5 vs 29 months for pHGGs with moderate/strong vs negative/weak IGF-1R (p = 0.011). Secondly, we tested IGF-1R inhibitor BMS-754807 in HGG cells, finding minimal radiosensitisation of 2/3 aHGG cell lines (dose enhancement ratios DERs < 1.60 at 2–8 Gy), and greater radiosensitisation of 2/2 pHGG cell lines (DERs ≤ 4.16). BMS-754807 did not influence radiation-induced apoptosis but perturbed the DNA damage response with altered induction/resolution of γH2AX, 53BP1 and RAD51 foci. These data indicate that IGF-1R promotes radioresistance in pHGG, potentially contributing to the association of IGF-1R with adverse outcome and suggesting IGF-1R as a candidate treatment target in pHGG.
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spelling pubmed-70542652020-12-20 Type 1 IGF receptor associates with adverse outcome and cellular radioresistance in paediatric high-grade glioma Simpson, Aaron D. Soo, Ying Wei Jenetta Rieunier, Guillaume Aleksic, Tamara Ansorge, Olaf Jones, Chris Macaulay, Valentine M. Br J Cancer Brief Communication High-grade glioma (HGG) is highly resistant to therapy, prompting us to investigate the contribution of insulin-like growth factor receptor (IGF-1R), linked with radioresistance in other cancers. IGF-1R immunohistochemistry in 305 adult HGG (aHGG) and 103 paediatric/young adult HGG (pHGG) cases revealed significant association with adverse survival in pHGG, with median survival of 13.5 vs 29 months for pHGGs with moderate/strong vs negative/weak IGF-1R (p = 0.011). Secondly, we tested IGF-1R inhibitor BMS-754807 in HGG cells, finding minimal radiosensitisation of 2/3 aHGG cell lines (dose enhancement ratios DERs < 1.60 at 2–8 Gy), and greater radiosensitisation of 2/2 pHGG cell lines (DERs ≤ 4.16). BMS-754807 did not influence radiation-induced apoptosis but perturbed the DNA damage response with altered induction/resolution of γH2AX, 53BP1 and RAD51 foci. These data indicate that IGF-1R promotes radioresistance in pHGG, potentially contributing to the association of IGF-1R with adverse outcome and suggesting IGF-1R as a candidate treatment target in pHGG. Nature Publishing Group UK 2019-12-20 2020-03-03 /pmc/articles/PMC7054265/ /pubmed/31857716 http://dx.doi.org/10.1038/s41416-019-0677-1 Text en © The Author(s), under exclusive licence to Cancer Research UK 2019 https://creativecommons.org/licenses/by/4.0/Note This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
spellingShingle Brief Communication
Simpson, Aaron D.
Soo, Ying Wei Jenetta
Rieunier, Guillaume
Aleksic, Tamara
Ansorge, Olaf
Jones, Chris
Macaulay, Valentine M.
Type 1 IGF receptor associates with adverse outcome and cellular radioresistance in paediatric high-grade glioma
title Type 1 IGF receptor associates with adverse outcome and cellular radioresistance in paediatric high-grade glioma
title_full Type 1 IGF receptor associates with adverse outcome and cellular radioresistance in paediatric high-grade glioma
title_fullStr Type 1 IGF receptor associates with adverse outcome and cellular radioresistance in paediatric high-grade glioma
title_full_unstemmed Type 1 IGF receptor associates with adverse outcome and cellular radioresistance in paediatric high-grade glioma
title_short Type 1 IGF receptor associates with adverse outcome and cellular radioresistance in paediatric high-grade glioma
title_sort type 1 igf receptor associates with adverse outcome and cellular radioresistance in paediatric high-grade glioma
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054265/
https://www.ncbi.nlm.nih.gov/pubmed/31857716
http://dx.doi.org/10.1038/s41416-019-0677-1
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