Biomolecular Surfaces for the Capture and Reprogramming of Circulating Tumor Cells

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摘要 CirculatingTumorCells(CTC)havethepotentialtobeusedclinicallyasadiagnostictoolandatreatmenttoolinthefieldofoncology.Asadiagnostictool,CTCmaybeusedtoindicatethepresenceofatumorbeforeitislargeenoughtocausenoticeablesymptoms.Asatreatmenttool,CTCisolatedfrompatientsmaybeusedtotesttheefficacyofchemotherapyoptionstopersonalizepatienttreatment.Onewayfortumorstospreadisthroughmetastasisviathecirculatorysystem.CTCareabletoexploitthenaturalleukocyterecruitmentprocessthatisinitiallymediatedbyrollingontransientselectinbonds.OurcapturedevicestakeadvantageofthisnaturallyoccurringrecruitmentsteptoisolateCTCfromwholebloodbyflowingsamplesthroughselectinandantibody-coatedmicrotubes.Wholebloodwasspikedwithaknownconcentrationoflabeledcancercellsandthenperfusedthroughpre-coatedmicrotubes.Microtubeswerethenrinsedtoremoveunboundcellsandthenumberoflabeledcellscapturedonthelumenwasassessed.CTCweresuccessfullycapturedfromwholebloodataclinicallyrelevantlevelontheorderof10cellspermL.Combinationtubeswithselectinandantibodycoatedsurfaceexhibitedhighercaptureratethantubescoatedwithselectinaloneorantibodyalone.Additionally,CTCcapturewasdemonstratedwiththeKG1ahematopoieticcelllineandtheDU145epithelialcellline.Thus,theinvivoprocessofselectin-mediatedCTCrecruitmenttodistantvesselwallscanbeusedinvitrototargetCTCtoatubelumen.ThebiomolecularcoatingscanalsobeusedtocaptureCTCofhematopoieticandepithelialtumororiginandisdemonstratedtosensitivitiesdowntotheorderof10CTCpermL.Inarelatedstudyaimedatreducingthebloodbornemetastaticcancerload,wehaveshownthatcellscapturedtoasurfacecanbeneutralizedbyareceptor-mediatedbiochemicalsignal.IntheproposedmethodwehaveshownthatusingacombinedselectinandTRAIL(TNFRelatedApoptosisInducingLigandorApo2L)functionalizedsurfaceweareabl
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出版日期 2009年04月14日(中国期刊网平台首次上网日期,不代表论文的发表时间)
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