简介:Objective:Theepidermalgrowthfactorreceptor(EGFR)inhibitorsmonoclonalantibodies(MoAbs)havealreadyshownthetherapeuticeffectivenessinpatientswithmetastaticcolorectalcancer(mCRC).Butmanypatientsresisttothetreatment.Theaimofthismeta-analysiswastoassessEGFRgenecopynumber(GCN)asacandidatepredictivebiomarkerforresistancetoanti-EGFRMoAbsinmCRCtreatment.Methods:SystematiccomputerizedsearchesofthePubMed,EMBaseandCochraneLibrarywereperformed.Theprimaryendpointwasobjectiveresponserate(ORR).Thesecondendpointsincludedprogression-freesurvival(PFS),andoverallsurvival(OS).Thepooledoddratio(OR)andpooledsensitivity,specificity,andsummaryreceiveroperatorcharacteristic(SROC)forORRwereestimated.Thepooledhazardratios(HR)forPFSandOSwerealsocalculated.Results:Fourteenstudieswith1,021patientswereincluded.IncreasedEGFRGCNwasassociatedwithincreasedORR(OR=6.905;95%CI:4.489-10.620).Itwasalsofoundinwild-typeKRASmCRCpatients,withthepooledORof8.133(95%CI:4.316-15.326).GCNhasmediumvalueforpredictingORR,withthepooledsensitivityof0.79(95%CI:0.73-0.84),thepooledspecificityof0.59(95%CI:0.55-0.62).InwildtypeKRASmCRCpatients,thesensitivityandthespecificitywere0.80(95%CI:0.70-0.87)and0.60(95%CI:0.53-0.66),respectively.IncreasedEGFRGCNwasassociatedwithincreasedPFS(HR=0.557;95%CI:0.382-0.732)andOS(HR=0.579;95%CI:0.422-0.737).Conclusions:Thismeta-analysissuggeststhatEGFRGCNrepresentsapredictivebiomarkerfortumorresponseinmCRCpatientstreatedwithMoAbsregardlessofKRASmutation.mCRCpatientswithincreasedEGFRGCNaremorelikelytohaveabetterresponse,PFS,andOSwhentreatedwithcetuximaborpanitumumab.
简介:Objective:Weretrospectivelyanalyzedtheclinicalprognosticvalueofthe8theditionoftheAmericanJointCommitteeonCancer(AJCC)stagingsystemforluminalAbreastcancer.Methods:Usingboththeanatomicandprognosticstaginginthe8theditionofAJCCcancerstagingsystem,werestagedpatientswithluminalAbreastcancertreatedattheBreastDiseaseCenter,PekingUniversityFirstHospitalfrom2008to2014.Follow-updataincluding5-yeardiseasefreesurvival(DFS),overallsurvival(OS)andotherclinic-pathologicaldatawerecollectedtoanalyzethedifferencesbetweenthetwostagingsubgroups.Results:Thisstudyincluded421patientswithluminalAbreastcancer(medianfollow-up,61months).The5-yearDFSandOSrateswere98.3%and99.3%,respectively.Significantdifferencesin5-yearDFSbutnotOSwereobservedbetweendifferentanatomicdiseasestages.Significantdifferenceswereobservedinboth5-yearDFSandOSbetweendifferentprognosticstages.Applicationoftheprognosticstagingsystemresultedinassignmentof175of421patients(41.6%)toadifferentgroupcomparedtotheiroriginalanatomicstages.Intotal,102of103patientswithanatomicstageIIAchangedtoprognosticstageIB,and24of52patientswithanatomicstageIIBchangedtoprognosticstageIB,while1changedtoprognosticstageIIIB.Twenty-twoof33patientswithanatomicstageIIIAweredown-stagedtoIIAwhenstagedbyprognosticstagingsystem,andtheother11patientsweredown-stagedtoIIB.TwopatientswithanatomicstageIIIBweredown-stagedtoIIIA.AmongsevenpatientswithanatomicstageIIICcancer,twoweredown-stagedtoIIIAandfourweredown-stagedtostageIIIB.Conclusions:The8theditionofAJCCprognosticstagingsystemisanimportantsupplementtothebreastcancerstagingsystem.Moreclinicaltrialsareneededtoproveitsabilitytoguideselectionofpropersystemictherapyandpredictprognosisofbreastcancer.
简介:Objective:ToanalyzethedifferentiallyexpressedcDNAsequencesrelatedtochlorophyllin(CHL)mediatedinhibitionofmalignanttransformationofhumanbronchia1epithelialcellline(16HBE).Methods:16HBEcellstreatedwithchlorophyllinandanti-BPDEwereconductedastester,16HBEcellstreatedonlywithanti-BPDEwereconductedasdriver,andcDNArepresentationaldifferenceanalysis(cDNARDA)wasusedtocomparethedifferentialgeneexpressionbetweenthetwokindsofcells.ThecDNAfragmentswereligatedtopGEM-TvectorandtransformedintoJM109bacteria.TheplasmidDNAwassequencedandcomparedwithdatabaseinGenBankbyBLASTN.Results:Amongthe5clonedcDNAsequences,threewerenovelandwereregisteredindbESTdatabase,twoshowedsequencehomologytoalpha-enolaseandanewlyfoundgeneribosomalproteinS18/S6-like.Conclusion:These5cDNAsequencesmightplayimportantrolesinantitransformingeffectofchlorophyllin.
简介:Objective:Tocomparetheefficacyandadverseeffectsofpaclitaxel-etoposide-carboplatin/cisplatin(TEP/TCE)regimenwiththoseofetoposide-carboplatin/cisplatin(EP/CE)regimenasfirst-linetreatmentforcombinedsmall-celllungcancer(CSCLC).Methods:Aretrospectivestudywasconductedon62CSCLCpatientswhoweretreatedatTianjinMedicalUniversityCancerInstituteandHospitalfromJuly2000toApril2013andadministeredwithTEP/TCEregimen(n=19)orEP/CEregimen(n=43)asfirst-lineCSCLCtreatment.Allpatientsreceivedmorethantwocyclesofchemotherapy,andtheresponsewasevaluatedeverytwocycles.Theprimaryendpointwasoverallsurvival(OS),andthesecondaryendpointswereprogression-freesurvival(PFS),objectiveresponserate(ORR),diseasecontrolrate(DCR),andadverseeffects.Results:ORRbetweentheTEP/TCEandEP/CEgroupsshowedastatisticaldifference(90%vs.53%,P=0.033).BothgroupsfailedtoreachastatisticaldifferenceinDCR(100%vs.86%,P=0.212).ThemedianPFSandOSoftheTEP/TCEgroupwereslightlylongerthanthoseoftheEP/CEgroup,althoughbothgroupsfailedtoreachastatisticaldifference(10.5vs.8.9months,P=0.484;24.0vs.17.5months,P=0.457).However,stratifiedanalysisindicatedthatthePFSofpatientswithstagesIIIandIVCSCLCshowedmarginallysignificantdifferencebetweentheTEP/TCEandEP/CEgroups(19.5vs.7.6months;P=0.071).BothratesofgradeIVbonemarrowdepressionandterminationofchemotherapyintheTEP/TCEgroupweresignificantlyhigherthanthoseintheEP/CEgroup(26.3%vs.7.0%,P=0.036;31.6%vs.14.7%,P=0.004).Conclusion:TheTEP/TCEregimenmaynotbepreferredforCSCLC,andthisthree-drugregimenrequiresfurtherexplorationandresearch.Todate,theEP/CEregimenremainsthestandardtreatmentforCSCLCpatients.
简介:Objective:Ameta-analysiswasperformedtoaugmenttheinsufficientdataontheimpactofmutativeEGFRdownstreamphosphatidylinositol-3-kinase(PI3K)andmitogen-activatedproteinkinase(MAPK)pathwaysontheclinicalefficiencyofepidermalgrowthfactorreceptortyrosinekinaseinhibitor(EGFR-TKI)treatmentofnon-smallcelllungcancer(NSCLC)patients.Methods:NetworkdatabaseswereexploredinApril,2015.PapersthatinvestigatedtheclinicaloutcomesofNSCLCpatientstreatedwithEGFR-TKIsaccordingtothestatusofK-rasand/orPIK3CAgenemutationwereincluded.Aquantitativemeta-analysiswasconductedusingstandardstatisticalmethods.Oddsratios(ORs)forobjectiveresponserate(ORR)andhazardratios(HRs)forprogression-freesurvival(PFS)andoverallsurvival(OS)werecalculated.Results:MutationinK-rassignificantlypredictedpoorORR[OR=0.22;95%confidenceinterval(CI),0.13-0.35],shorterPFS(HR=1.56;95%CI,1.27-1.92),andshorterOS(HR=1.59;95%CI,1.33-1.91)inNSCLCpatientstreatedwithEGFR-TKIs.MutantPIK3CAsignificantlypredictedshorterOS(HR=1.83;95%CI,1.05-3.20),showedpoorORR(OR=0.70;95%CI,0.22-2.18),andshorterPFS(HR=1.79;95%CI,0.91-3.53)inNSCLCpatientstreatedwithEGFR-TKIs.Conclusion:K-rasmutationadverselyaffectedtheclinicalresponseandsurvivalofNSCLCpatientstreatedwithEGFRTKIs.PIK3CAmutationshowedsimilartrends.InadditiontoEGFR,addingK-rasandPIK3CAasroutinegenebiomarkersinclinicalgeneticanalysisisvaluabletooptimizetheeffectivenessofEGFR-TKIregimensandidentifyoptimalpatientswhowillbenefitfromEGFR-TKItreatment.