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dc.contributor.authorShaw, Greg L.
dc.contributor.authorWhitaker, Hayley
dc.contributor.authorCorcoran, Marie
dc.contributor.authorDunning, Mark J.
dc.contributor.authorLuxton, Hayley
dc.contributor.authorKay, Jonathan
dc.contributor.authorMassie, Charlie E.
dc.contributor.authorMiller, Jodi L.
dc.contributor.authorLamb, Alastair D.
dc.contributor.authorRoss-Adams, Helen
dc.contributor.authorRussell, Roslin
dc.contributor.authorNelson, Adam W.
dc.contributor.authorEldridge, Matthew D.
dc.contributor.authorLynch, Andrew G.
dc.contributor.authorRamos-Montoya, Antonio
dc.contributor.authorMills, Ian G.
dc.contributor.authorTaylor, Angela E.
dc.contributor.authorArlt, Wiebke
dc.contributor.authorShah, Nimish
dc.contributor.authorWarren, Anne Y.
dc.contributor.authorNeal, David E.
dc.date.accessioned2017-08-11T15:30:08Z
dc.date.available2017-08-11T15:30:08Z
dc.date.issued2016-08
dc.identifier.citationShaw , G L , Whitaker , H , Corcoran , M , Dunning , M J , Luxton , H , Kay , J , Massie , C E , Miller , J L , Lamb , A D , Ross-Adams , H , Russell , R , Nelson , A W , Eldridge , M D , Lynch , A G , Ramos-Montoya , A , Mills , I G , Taylor , A E , Arlt , W , Shah , N , Warren , A Y & Neal , D E 2016 , ' The early effects of rapid androgen deprivation on human prostate cancer ' , European Urology , vol. 70 , no. 2 , pp. 214-218 . https://doi.org/10.1016/j.eururo.2015.10.042en
dc.identifier.issn0302-2838
dc.identifier.otherPURE: 250730062
dc.identifier.otherPURE UUID: 685db44e-bf36-41e0-8921-3f0cf325dbc5
dc.identifier.otherScopus: 84960893239
dc.identifier.otherORCID: /0000-0002-7876-7338/work/35946870
dc.identifier.urihttp://hdl.handle.net/10023/11434
dc.descriptionThe authors thank CRUK; the NIHR; the Academy of Medical Sciences (RG:63397); the National Cancer Research Prostate Cancer: Mechanisms of Progression and Treatment (ProMPT) collaborative (G0500966/75466); Hutchison Whampoa Limited; the Human Research Tissue Bank (Addenbrooke’s Hospital, supported by the NIHR Cambridge BRC); and Cancer Research UK.en
dc.description.abstractThe androgen receptor (AR) is the dominant growth factor in prostate cancer (PCa). Therefore, understanding how ARs regulate the human transcriptome is of paramount importance. The early effects of castration on human PCa have not previously been studied 27 patients medically castrated with degarelix 7 d before radical prostatectomy. We used mass spectrometry, immunohistochemistry, and gene expression array (validated by reverse transcription-polymerase chain reaction) to compare resected tumour with matched, controlled, untreated PCa tissue. All patients had levels of serum androgen, with reduced levels of intraprostatic androgen at prostatectomy. We observed differential expression of known androgen-regulated genes (TMPRSS2, KLK3, CAMKK2, FKBP5). We identified 749 genes downregulated and 908 genes upregulated following castration. AR regulation of α-methylacyl-CoA racemase expression and three other genes (FAM129A, RAB27A, and KIAA0101) was confirmed. Upregulation of oestrogen receptor 1 (ESR1) expression was observed in malignant epithelia and was associated with differential expression of ESR1-regulated genes and correlated with proliferation (Ki-67 expression). Patient summary :  This first-in-man study defines the rapid gene expression changes taking place in prostate cancer (PCa) following castration. Expression levels of the genes that the androgen receptor regulates are predictive of treatment outcome. Upregulation of oestrogen receptor 1 is a mechanism by which PCa cells may survive despite castration.
dc.format.extent5
dc.language.isoeng
dc.relation.ispartofEuropean Urologyen
dc.rights© 2015 European Association of Urology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).en
dc.subjectAndrogen receptoren
dc.subjectCastrationen
dc.subjectClinical trialen
dc.subjectGene transcriptionen
dc.subjectImmunohistochemistryen
dc.subjectProstate canceren
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectUrologyen
dc.subjectNDASen
dc.subject.lccRC0254en
dc.titleThe early effects of rapid androgen deprivation on human prostate canceren
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Statisticsen
dc.identifier.doihttps://doi.org/10.1016/j.eururo.2015.10.042
dc.description.statusPeer revieweden


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