循环肿瘤细胞最新进展PPT文件格式下载.ppt

循环肿瘤细胞最新进展PPT文件格式下载.ppt

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CD45（+）andCD66（+）lBasicmodes:

positiveselectionmode:

anti-EpCAMnegativeselectionmode:

anti-CD45anti-CD66CTC-iChipsystemCombinesthestrengthsofmicrofluidicsforrarecellhandingandmagnetic-basedcellsorting.lMagneticlabelingofcellsinbloodcells.（pos-vsneg-）lDebulkingbyseparationofnucleatedcellsfromtheenucleated.lAlignmentofnucleatedcellswithinamicrofluidicchannel.lDeflectionofmagneticallytaggedcellsintoacollectionchannel.TheSpecialconditionsforCTCcultrueBloodsamples:

patientswithmetastaticER（+）Nonadherentcultureconditions（critical）Serum-freesupplementedEGFandFGFunderhypoxicconditions（4%O2）Establishlong-termoligoclonalCTC（sustaimedinvitro6months）ResultsofCTCculturelCTClinescanonlybegeneratedfrompatientswhowereeitherofftherapyorprogressingontreatment.andcannotbegeneratedfrompatientswhowererespondingtotreatment.lForthreepatients,fouradditionalCTCcelllineswereestablishedfrombloodsamplesdrawnatmultipledifferenttimepointsduringtherapy.Inthesecases,CTCswereculturedonlywhenpatientswereprogressingontreatment.ResultsofCTCculturelCulturedCTCssharedcytologicalfeatureswiththematchedprimaryCTCscaptured.lConsisitentwithstandardCTCdefinitions:

CK（+）;

CD45（-）;

proliferativeindex30%（Ki67）；

initialdoublingtime:

3daysto3weeks.lFiveCTClinesretainedER（+）,BRx-07lostERexpresion,butregainedinXenografttumor.lCTC-derivedtumorssharedhistologicalandimmunohistochemicalfeatureswiththematchedprimarytumor.GeneanalysislRNAsequencinganalysis6culturedcelllines;

13commonlyusedbreastcancercelllines;

29uncluredsingleCTCs.lMutationanalysisSNaPShot:

primarytumor（140mutationsin25gene）NGSplatform:

CTCcultureandothermutation（1000genes）ResultsofgeneanalysisESR1（BRx-68）,TP53（BRx-68,61）andKRAS（BRx-42）areuniversallypresentinallindependentCTCcelllines.PIK3CA,KRASandFGFR2arearisingmutations.ThemutantallelefrequencesofTP53andESR1areincreaseduponprolongedculture.ChoosedrugtargetsESR1andPIK3CAfordrugsensitivitytest.ResultsofDrugSensitivitytestSomeCTCdrugsensitivitymeasurementswereconcordantwithclinicalhistory.ResultsofDrugSensitivity（BRx-68）SERMs（tamoxifen）andSERD（raloxifene）wereineffective,aloneorcombinedwithinhibitorsofPIK3-mTOR（everolimus）.HSP90inhibitorSTA9090demonstratedcytotoxicity,aloneorcombinitionwithSERMsorSERD.AlowdoseofSTA9090suppressedERlevel.?

ResultsofDrugSensitivity（BRx-07）CulturedCTCswerehighlysensitivetoPIK3CAandFGFR2inhibitors.CombinationsofPIK3CAandFGFRinhibitorsshowedcooperatoveeffects.?

iIGFRmitigatesensitivitytoiPI3K;

iHSP90stablizemutantkinases.ResultsofDrugSensitivity（BRx-07）DifferentFGFRmutationshavedifferentsensitivitytoPIK3CAandFGFR2inhibitors.ConclusionsStudypatternsofdrugsusceptibilitywithCTC,combinedwithgeneticcontext.Enablemonitoringofemergingsubcloneswithalterdmutationalanddrugsensitivityprofiles.DiscussionlSamples:

patientswithmetastatic/PVTTwhichstage?

lMode:

negativemode.lDrugtargets:

mutationalgeneanalysisLiuZixinwhichstage?

biomarkers?

AFP?