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dc.contributor.authorVlenterie, Men_US
dc.contributor.authorHillebrandt-Roeffen, MHSen_US
dc.contributor.authorSchaars, EWMen_US
dc.contributor.authorFlucke, UEen_US
dc.contributor.authorFleuren, EDGen_US
dc.contributor.authorNavis, ACen_US
dc.contributor.authorLeenders, WPJen_US
dc.contributor.authorVersleijen-Jonkers, YMHen_US
dc.contributor.authorvan der Graaf, WTAen_US
dc.date.accessioned2016-09-28T14:34:25Z
dc.date.issued2016-09en_US
dc.identifier.citationAnnals of surgical oncology, 2016, 23 (9), pp. 2745 - 2752en_US
dc.identifier.issn1068-9265en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/151
dc.identifier.eissn1534-4681en_US
dc.identifier.doi10.1245/s10434-016-5341-xen_US
dc.description.abstract<h4>Background</h4>In synovial sarcomas alterations in the cyclin D1-CDK4/6-Rb axis have been described. Also, β-catenin, a cyclin D1 regulator, is often overexpressed. Additionally, studies have shown that the t(X;18) translocation influences tumor behavior partly through cyclin D1 activation. We investigated how alterations in the cyclin D1-CDK4/6-Rb axis impact prognosis and studied effects of targeting this axis with the CDK4/6 inhibitor palbociclib.<h4>Methods</h4>Synovial sarcoma samples (n = 43) were immunohistochemically stained for β-catenin, cyclin D1, p16, p21, p27, Rb, and phospho-Rb. Fluorescent in situ hybridization (FISH) was performed to detect CCND1 amplification or translocation. In 4 synovial sarcoma cell lines sensitivity to palbociclib was investigated using cell viability assays, and effects on the sensitive cell lines were evaluated on protein level and by cell cycle arrest.<h4>Results</h4>Expression of nuclear phospho-Rb and nuclear β-catenin in the patient samples was associated with poor survival. FISH showed a sporadic translocation of CCND1 in a subset of tumors. An 8-fold CCND1 amplification was found in 1 cell line, but not in the patient samples investigated. Palbociclib effectively inhibited Rb-phosphorylation in 3 cell lines, resulting in an induction of a G1 arrest and proliferation block.<h4>Conclusions</h4>In this series nuclear phospho-Rb and nuclear β-catenin expression were negative prognostic factors. In vitro data suggest that palbociclib may be a potential treatment for a subset of synovial sarcoma patients. Whether this effect can be enhanced by combination treatment deserves further preclinical investigations.en_US
dc.formatPrint-Electronicen_US
dc.format.extent2745 - 2752en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectCell Line, Tumoren_US
dc.subjectHumansen_US
dc.subjectSarcoma, Synovialen_US
dc.subjectPiperazinesen_US
dc.subjectPyridinesen_US
dc.subjectCyclin D1en_US
dc.subjectRetinoblastoma Proteinen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectImmunohistochemistryen_US
dc.subjectSurvival Rateen_US
dc.subjectCell Proliferationen_US
dc.subjectPhosphorylationen_US
dc.subjectAdolescenten_US
dc.subjectFemaleen_US
dc.subjectMaleen_US
dc.subjectCyclin-Dependent Kinase Inhibitor p16en_US
dc.subjectCyclin-Dependent Kinase Inhibitor p21en_US
dc.subjectCyclin-Dependent Kinase Inhibitor p27en_US
dc.subjectbeta Cateninen_US
dc.subjectCyclin-Dependent Kinase 4en_US
dc.subjectCyclin-Dependent Kinase 6en_US
dc.subjectYoung Adulten_US
dc.subjectG1 Phase Cell Cycle Checkpointsen_US
dc.titleTargeting Cyclin-Dependent Kinases in Synovial Sarcoma: Palbociclib as a Potential Treatment for Synovial Sarcoma Patients.en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1245/s10434-016-5341-xen_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2016-09en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfAnnals of surgical oncologyen_US
pubs.issue9en_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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical and Translational Sarcoma
pubs.publication-statusPublisheden_US
pubs.volume23en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamClinical and Translational Sarcomaen_US
dc.contributor.icrauthorvan der Graaf, Wilhelminaen_US


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