dc.contributor.author | Simpson, AD | |
dc.contributor.author | Soo, YWJ | |
dc.contributor.author | Rieunier, G | |
dc.contributor.author | Aleksic, T | |
dc.contributor.author | Ansorge, O | |
dc.contributor.author | Jones, C | |
dc.contributor.author | Macaulay, VM | |
dc.date.accessioned | 2021-01-21T14:41:23Z | |
dc.date.issued | 2020-03-01 | |
dc.identifier.citation | British journal of cancer, 2020, 122 (5), pp. 624 - 629 | |
dc.identifier.issn | 0007-0920 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4300 | |
dc.identifier.eissn | 1532-1827 | |
dc.identifier.doi | 10.1016/j.bmcl.2017.04.085 | |
dc.description.abstract | 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. | |
dc.format | Print-Electronic | |
dc.format.extent | 624 - 629 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Humans | |
dc.subject | Glioma | |
dc.subject | Brain Neoplasms | |
dc.subject | DNA Damage | |
dc.subject | Pyrazoles | |
dc.subject | Triazines | |
dc.subject | Receptor, IGF Type 1 | |
dc.subject | Tissue Array Analysis | |
dc.subject | Immunohistochemistry | |
dc.subject | Signal Transduction | |
dc.subject | Radiation Tolerance | |
dc.subject | Neoplasm Grading | |
dc.title | Type 1 IGF receptor associates with adverse outcome and cellular radioresistance in paediatric high-grade glioma. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-11-19 | |
rioxxterms.versionofrecord | 10.1016/j.bmcl.2017.04.085 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2020-03 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | British journal of cancer | |
pubs.issue | 5 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Glioma Team | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Glioma Team | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Glioma Team | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Glioma Team | |
pubs.publication-status | Published | |
pubs.volume | 122 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Glioma Team | |
dc.contributor.icrauthor | Jones, Chris | |