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dc.contributor.authorCruz-Garcia, Len_US
dc.contributor.authorO'Brien, Gen_US
dc.contributor.authorDonovan, Een_US
dc.contributor.authorGothard, Len_US
dc.contributor.authorBoyle, Sen_US
dc.contributor.authorLaval, Aen_US
dc.contributor.authorTestard, Ien_US
dc.contributor.authorPonge, Len_US
dc.contributor.authorWoźniak, Gen_US
dc.contributor.authorMiszczyk, Len_US
dc.contributor.authorCandéias, SMen_US
dc.contributor.authorAinsbury, Een_US
dc.contributor.authorWidlak, Pen_US
dc.contributor.authorSomaiah, Nen_US
dc.contributor.authorBadie, Cen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2018-01-30T11:32:25Z
dc.date.accessioned2019-02-25T10:06:05Z
dc.date.issued2018-07en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/29787434en_US
dc.identifier00004032-201807000-00011en_US
dc.identifier.citationHealth Phys, 2018, 115 (1), pp. 90 - 101en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3081
dc.identifier.eissn1538-5159en_US
dc.identifier.doi10.1097/HP.0000000000000844en_US
dc.description.abstractFor triage purposes following a nuclear accident, blood-based gene expression biomarkers can provide rapid dose estimates for a large number of individuals. Ionizing-radiation-responsive genes are regulated through the DNA damage-response pathway, which includes activation of multiple transcription factors. Modulators of this pathway could potentially affect the response of these biomarkers and consequently compromise accurate dose estimation calculations. In the present study, four potential confounding factors were selected: cancer condition, sex, simulated bacterial infection (lipopolysaccharide), and curcumin, an anti-inflammatory/antioxidant agent. Their potential influence on the transcriptional response to radiation of the genes CCNG1 and PHPT1, two biomarkers of radiation exposure ex vivo, was assessed. First, both CCNG1 and PHPT1 were detected in vivo in blood samples from radiotherapy patients and as such were validated as biomarkers of exposure. Importantly, their basal expression level was slightly but significantly affected in vivo by patients' cancer condition. Moreover, lipopolysaccharide stimulation of blood irradiated ex vivo led to a significant modification of CCNG1 and PHPT1 transcriptional response in a dose- and time-dependent manner with opposite regulatory effects. Curcumin also affected CCNG1 and PHPT1 transcriptional response counteracting some of the radiation induction. No differences were observed based on sex. Dose estimations calculated using linear regression were affected by lipopolysaccharide and curcumin. In conclusion, several confounding factors tested in this study can indeed modulate the transcriptional response of CCNG1 and PHPT1 and consequently can affect radiation exposure dose estimations but not to a level which should prevent the biomarkers' use for triage purposes.en_US
dc.format.extent90 - 101en_US
dc.languageengen_US
dc.language.isoengen_US
dc.relation.replaceshttps://repository.icr.ac.uk/handle/internal/1034
dc.relation.replacesinternal/1034
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_US
dc.subjectAdulten_US
dc.subjectAgeden_US
dc.subjectAged, 80 and overen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectBiomarkersen_US
dc.subjectCase-Control Studiesen_US
dc.subjectCurcuminen_US
dc.subjectCyclin G1en_US
dc.subjectFemaleen_US
dc.subjectGene Expression Regulation, Neoplasticen_US
dc.subjectHumansen_US
dc.subjectLipopolysaccharidesen_US
dc.subjectMaleen_US
dc.subjectMiddle Ageden_US
dc.subjectNeoplasmsen_US
dc.subjectPhosphoric Monoester Hydrolasesen_US
dc.subjectRadiotherapy Dosageen_US
dc.subjectRadiotherapy, Intensity-Modulateden_US
dc.titleInfluence of Confounding Factors on Radiation Dose Estimation Using In Vivo Validated Transcriptional Biomarkers.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-01-29en_US
rioxxterms.versionofrecord10.1097/HP.0000000000000844en_US
rioxxterms.licenseref.startdate2018-07en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfHealth Physen_US
pubs.issue1en_US
pubs.notesNo embargoen_US
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 Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Clinical Academic Radiotherapy (Yarnold)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy
pubs.publication-statusPublisheden_US
pubs.volume115en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamClinical Academic Radiotherapy (Yarnold)en_US
icr.researchteamTargeted Therapyen_US
dc.contributor.icrauthorSomaiah, Navitaen_US
dc.contributor.icrauthorGothard, Loneen_US
dc.contributor.icrauthorBoyle, Susanen_US


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