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dc.contributor.authorRussell, S.
dc.contributor.authorDuquette, M.
dc.contributor.authorLiu, Joyce Ying
dc.contributor.authorDrapkin, Ronny I.
dc.contributor.authorLawler, Jack William
dc.contributor.authorPetrik, J.
dc.date.accessioned2018-03-27T18:57:46Z
dc.date.issued2014
dc.identifierQuick submit: 2015-01-02T18:28:43-05:00
dc.identifier.citationRussell, S., M. Duquette, J. Liu, R. Drapkin, J. Lawler, and J. Petrik. 2014. “Combined Therapy with Thrombospondin-1 Type I Repeats (3TSR) and Chemotherapy Induces Regression and Significantly Improves Survival in a Preclinical Model of Advanced Stage Epithelial Ovarian Cancer.” The FASEB Journal 29 (2) (November 13): 576–588. doi:10.1096/fj.14-261636.en_US
dc.identifier.issn0892-6638en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:35141011
dc.description.abstractMost women are diagnosed with epithelial ovarian cancer (EOC) at advanced stage, where therapies have limited effectiveness and the long-term survival rate is low. We evaluated the effects of combined antiangiogenic and chemotherapy treatments on advanced stage EOC. Treatment of EOC cells with a recombinant version of the thrombospondin-1 type I repeats (3TSR) induced more apoptotic cell death (36.5 ± 9.6%) in vitro compared to untreated controls (4.1 ± 1.4). In vivo, tumors were induced in an orthotopic, syngeneic mouse model of advanced stage EOC. Mice were treated with 3TSR (4 mg/kg per day) alone or in combination with chemotherapy drugs delivered with maximum tolerated dose or metronomic scheduling. Pretreatment with 3TSR induced tumor regression, normalized tumor vasculature, and improved uptake of chemotherapy drugs. Combination 3TSR and metronomic chemotherapy induced the greatest tumor regression (6.2-fold reduction in size compared to PBS-treated controls) and highest survival when treatment was initiated at advanced stage. 3TSR binding to its receptor, CD36 (cluster of differentiation 36), increased binding of CD36 and SHP-1, which significantly inhibited phosphorylation of the VEGF receptor. In this study, we describe a novel treatment approach and mechanism of action with 3TSR and chemotherapy that induces regression of advanced stage EOC and significantly improves survival.—Russell, S., Duquette, M., Liu, J., Drapkin, R., Lawler, J., Petrik, J. Combined therapy with thrombospondin-1 type I repeats (3TSR) and chemotherapy induces regression and significantly improves survival in a preclinical model of advanced stage epithelial ovarian cancer.en_US
dc.language.isoen_USen_US
dc.publisherFASEBen_US
dc.relation.isversionofdoi:10.1096/fj.14-261636en_US
dash.licenseMETA_ONLY
dc.subjectantiangiogenicen_US
dc.subjectmetronomicen_US
dc.subjectvessel normalizationen_US
dc.titleCombined therapy with thrombospondin-1 type I repeats (3TSR) and chemotherapy induces regression and significantly improves survival in a preclinical model of advanced stage epithelial ovarian canceren_US
dc.typeJournal Articleen_US
dc.date.updated2015-01-02T23:28:43Z
dc.description.versionVersion of Recorden_US
dc.rights.holderSamantha Russel, Mark Duquette, Joyce Liu, Ronny Drapkin, Jack Lawler, Jim Petrik
dc.relation.journalThe FASEB Journalen_US
dash.depositing.authorLawler, Jack William
dash.embargo.until10000-01-01
dc.identifier.doi10.1096/fj.14-261636*
workflow.legacycommentsConsider rejecting. Little options for posting. oap.needman need preprint specifically, hence above comment.en_US
dash.contributor.affiliatedLiu, Joyce
dash.contributor.affiliatedLawler, Jack
dash.contributor.affiliatedDrapkin, Ronny


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