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dc.contributor.authorKoussounadis, A.
dc.contributor.authorLangdon, S. P.
dc.contributor.authorHarrison, D. J.
dc.contributor.authorSmith, V Anne
dc.date.accessioned2015-06-09T23:10:56Z
dc.date.available2015-06-09T23:10:56Z
dc.date.issued2014-06-10
dc.identifier.citationKoussounadis , A , Langdon , S P , Harrison , D J & Smith , V A 2014 , ' Chemotherapy-induced dynamic gene expression changes in vivo are prognostic in ovarian cancer ' , British Journal of Cancer , vol. 110 , no. 12 , pp. 2975-2984 . https://doi.org/10.1038/bjc.2014.258en
dc.identifier.issn0007-0920
dc.identifier.otherPURE: 145290939
dc.identifier.otherPURE UUID: c5c1e0c8-ca8f-4cce-b29c-4a7e910c16ac
dc.identifier.otherWOS: 000338181200018
dc.identifier.otherScopus: 84902537661
dc.identifier.otherORCID: /0000-0002-0487-2469/work/32209213
dc.identifier.otherWOS: 000338181200018
dc.identifier.otherORCID: /0000-0001-9041-9988/work/64034228
dc.identifier.urihttp://hdl.handle.net/10023/6793
dc.descriptionThis work was supported by Medical Research Scotland (FRG353 to VAS), the FP7-Directorate-General for Research and Innovation of the European Commission (EU HEALTH-F4-2012-305033 to Coordinating Action Systems Medicine to DJH); the Chief Scientist Office of Scotland (to DJH) and the Scottish Funding Council (to DJH and SPL).en
dc.description.abstractBackground: The response of ovarian cancer patients to carboplatin and paclitaxel is variable, necessitating identification of biomarkers that can reliably predict drug sensitivity and resistance. In this study, we sought to identify dynamically controlled genes and pathways associated with drug response and its time dependence. Methods: Gene expression was assessed for 14 days post-treatment with carboplatin or carboplatin–paclitaxel in xenografts from two ovarian cancer models: platinum-sensitive serous adenocarcinoma-derived OV1002 and a mixed clear cell/endometrioid carcinoma-derived HOX424 with reduced sensitivity to platinum. Results: Tumour volume reduction was observed in both xenografts, but more dominantly in OV1002. Upregulated genes in OV1002 were involved in DNA repair, cell cycle and apoptosis, whereas downregulated genes were involved in oxygen-consuming metabolic processes and apoptosis control. Carboplatin–paclitaxel triggered a more comprehensive response than carboplatin only in both xenografts. In HOX424, apoptosis and cell cycle were upregulated, whereas Wnt signalling was inhibited. Genes downregulated after day 7 from both xenografts were predictive of overall survival. Overrepresented pathways were also predictive of outcome. Conclusions: Late expressed genes are prognostic in ovarian tumours in a dynamic manner. This longitudinal gene expression study further elucidates chemotherapy response in two models, stressing the importance of delayed biomarker detection and guiding optimal timing of biopsies.
dc.format.extent10
dc.language.isoeng
dc.relation.ispartofBritish Journal of Canceren
dc.rightsCopyright 2014 Cancer Research UK. All rights reserved. This paper is licensed under the Creative Commons Attribution-NonCommercial-Share-Alike 3.0 licence, subject to the conditions listed at http://creativecommons.org/licences/by-nc-sa/3.0/. The CC licence comes into effect 12 months after print publication (10/6/15).en
dc.subjectOvarian canceren
dc.subjectCarboplatinen
dc.subjectPaclitaxelen
dc.subjectXenograften
dc.subjectPrognosisen
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectBDCen
dc.subject.lccRC0254en
dc.titleChemotherapy-induced dynamic gene expression changes in vivo are prognostic in ovarian canceren
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Scottish Oceans Instituteen
dc.contributor.institutionUniversity of St Andrews.Institute of Behavioural and Neural Sciencesen
dc.contributor.institutionUniversity of St Andrews.Centre for Research into Ecological & Environmental Modellingen
dc.contributor.institutionUniversity of St Andrews.Centre for Biological Diversityen
dc.identifier.doihttps://doi.org/10.1038/bjc.2014.258
dc.description.statusPeer revieweden
dc.date.embargoedUntil2015-06-10


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