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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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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. |
format | Online Article Text |
id | pubmed-7054265 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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