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dc.contributor.authorSimpson, AD
dc.contributor.authorSoo, YWJ
dc.contributor.authorRieunier, G
dc.contributor.authorAleksic, T
dc.contributor.authorAnsorge, O
dc.contributor.authorJones, C
dc.contributor.authorMacaulay, VM
dc.date.accessioned2021-01-21T14:41:23Z
dc.date.issued2020-03
dc.identifier.citationBritish journal of cancer, 2020, 122 (5), pp. 624 - 629
dc.identifier.issn0007-0920
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4300
dc.identifier.eissn1532-1827
dc.identifier.doi10.1016/j.bmcl.2017.04.085
dc.description.abstractHigh-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.formatPrint-Electronic
dc.format.extent624 - 629
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectHumans
dc.subjectGlioma
dc.subjectBrain Neoplasms
dc.subjectDNA Damage
dc.subjectPyrazoles
dc.subjectTriazines
dc.subjectReceptor, IGF Type 1
dc.subjectTissue Array Analysis
dc.subjectImmunohistochemistry
dc.subjectSignal Transduction
dc.subjectRadiation Tolerance
dc.subjectNeoplasm Grading
dc.titleType 1 IGF receptor associates with adverse outcome and cellular radioresistance in paediatric high-grade glioma.
dc.typeJournal Article
dcterms.dateAccepted2019-11-19
rioxxterms.versionofrecord10.1016/j.bmcl.2017.04.085
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-03
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBritish journal of cancer
pubs.issue5
pubs.notesNot 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-statusPublished
pubs.volume122en_US
pubs.embargo.termsNot known
icr.researchteamGlioma Teamen_US
dc.contributor.icrauthorJones, Chrisen


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