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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.abstractIn 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.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.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.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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