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dc.contributor.authorKanabur, Pratiken_US
dc.contributor.authorGuo, Sujuanen_US
dc.contributor.authorSimonds, Gary S.en_US
dc.contributor.authorKelly, Deborah F.en_US
dc.contributor.authorGourdie, Robert G.en_US
dc.contributor.authorVerbridge, Scotten_US
dc.contributor.authorSheng, Zhien_US
dc.date.accessioned2017-06-07T20:43:54Z
dc.date.available2017-06-07T20:43:54Z
dc.date.issued2016-12-27en_US
dc.identifier.issn1949-2553en_US
dc.identifier.urihttp://hdl.handle.net/10919/77941
dc.description.abstractThe dismal prognosis of glioblastoma is, at least in part, attributable to the difficulty in eradicating glioblastoma stem cells (GSCs). However, whether this difficulty is caused by the differential responses of GSCs to drugs remains to be determined. To address this, we isolated and characterized ten GSC lines from established cell lines, xenografts, or patient specimens. Six lines formed spheres in a regular culture condition, whereas the remaining four lines grew as monolayer. These adherent lines formed spheres only in plates coated with poly-2-hydroxyethyl methacrylate. The self-renewal capabilities of GSCs varied, with the cell density needed for sphere formation ranging from 4 to 23.8 cells/well. Moreover, a single non-adherent GSC either remained quiescent or divided into two cells in four-seven days. The stem cell identity of GSCs was further verified by the expression of nestin or glial fibrillary acidic protein. Of the two GSC lines that were injected in immunodeficient mice, only one line formed a tumor in two months. The protein levels of NOTCH1 and platelet derived growth factor receptor alpha positively correlated with the responsiveness of GSCs to γ-secretase inhibitor IX or imatinib, two compounds that inhibit these two proteins, respectively. Furthermore, a combination of temozolomide and a connexin 43 inhibitor robustly inhibited the growth of GSCs. Collectively, our results demonstrate that patient-derived GSCs exhibit different growth rates in culture, possess differential capabilities to form a tumor, and have varied responses to targeted therapies. Our findings underscore the importance of patient-derived GSCs in glioblastoma research and therapeutic development.en
dc.format.extent86406 - 86419 (14) page(s)en_US
dc.languageEnglishen_US
dc.publisherImpact Journals Llcen_US
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000391422500060&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en_US
dc.rightsCreative Commons Attribution 3.0 Unported (CC BY 3.0)*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/*
dc.subjectOncologyen_US
dc.subjectCell Biologyen_US
dc.subjectglioblastomaen_US
dc.subjectglioblastoma stem cellsen_US
dc.subjectpatient-derived glioblastoma stem cellsen_US
dc.subjecttargeted therapiesen_US
dc.subjectTUMOR-INITIATING CELLSen_US
dc.subjectRECURRENT GLIOBLASTOMAen_US
dc.subjectMALIGNANT GLIOMAen_US
dc.subjectXENOGRAFT MODELSen_US
dc.subjectGROWTH-FACTORen_US
dc.subjectCANCERen_US
dc.subjectNOTCHen_US
dc.subjectHETEROGENEITYen_US
dc.subjectTEMOZOLOMIDEen_US
dc.subjectINHIBITIONen_US
dc.titlePatient-derived glioblastoma stem cells respond differentially to targeted therapiesen_US
dc.typeArticle - Refereed
dc.description.versionPublished (Publication status)en_US
dc.title.serialONCOTARGETen_US
dc.identifier.doihttps://doi.org/10.18632/oncotarget.13415
dc.contributor.committeechairRodgers, Cara M.en
dc.identifier.volume7en_US
dc.identifier.issue52en_US
dc.identifier.orcidGourdie, RG [0000-0001-6021-0796]en_US
dc.identifier.orcidVerbridge, SS [0000-0002-4074-8799]en_US
dc.identifier.orcidSheng, Z [0000-0002-0029-8666]en_US
pubs.organisational-group/Virginia Tech
pubs.organisational-group/Virginia Tech/All T&R Faculty
pubs.organisational-group/Virginia Tech/Engineering
pubs.organisational-group/Virginia Tech/Engineering/Biomedical Engineering and Mechanics
pubs.organisational-group/Virginia Tech/Engineering/COE T&R Faculty
pubs.organisational-group/Virginia Tech/Faculty of Health Sciences
pubs.organisational-group/Virginia Tech/University Research Institutes
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Fralin Affiliated Faculty
pubs.organisational-group/Virginia Tech/University Research Institutes/Virginia Tech Carilion Research Institute


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Creative Commons Attribution 3.0 Unported (CC BY 3.0)
License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)