简介：Objective:Theelevatedincidenceofobesityhasbeenparalleledwithhigherrisksofbreastcancer.Highadiposityincreasesleptinsecretionfromadiposetissue,whichinturnincreasescancercellproliferation.Theinterplaybetweenleptinandestrogenisoneofthemechanismsthroughwhichleptininfluencesbreastcarcinogenesis.Anunbalancedestrogenmetabolismincreasestheformationsofcatecholestrogenquinones,DNAadducts,andcancermutations.ThisstudyaimstoinvestigatetheeffectofleptinonsomeestrogenmetabolicenzymesandDNAadductioninbreastcancercells.Methods:Highperformanceliquidchromatography(HPLC)wasperformedtoanalyzetheDNAadducts4-OHE1[E2]-1-N3adenineand4-OHE1[E2]-1-N7guanine.Reportergeneassay,realtimereversetranscriptionpolymerasechainreaction(realtimeRT-PCR),andWesternblotwereusedtoassesstheexpressionofestrogenmetabolizinggenesandenzymes:CytochromeP-4501B1(CYP1B1),Nicotinamideadeninedinucleotidephosphate-quinoneoxidoreductase1(NQO1),andCatechol-O-methyltransferase(COMT).Results:LeptinsignificantlyincreasedtheDNAadducts4-OHE1[E2]-1-N3adenineand4-OHE1[E2]-1-N7guanine.Furthermore,leptinsignificantlyupregulatedCYP1B1promoteractivityandproteinexpression.TheluciferasepromoteractivitiesofNQO1andmRNAlevelsweresignificantlyreduced.Moreover,leptingreatlyreducedthereporteractivitiesoftheCOMT-P1andCOMT-P2promotersanddiminishedtheproteinexpressionofCOMT.Conclusions:LeptinincreasesDNAadductlevelsinbreastcancercellspartlybyaffectingkeygenesandenzymesinvolvedinestrogenmetabolism.Thus,increasedfocusshouldbedirectedtowardleptinanditseffectsontheestrogenmetabolicpathwayasaneffectiveapproachagainstbreastcancer.

简介：Objective:ToevaluatethefeasibilityofDNAimagecytometry(DNA-ICM)asaprimaryscreeningmethodforesophagealsquamouscellcancer(ESCC).Methods:Atotalof5,382localresidentsaged40–69yearsfromthreehigh-riskareasinChina(LinzhouinHenanprovince,FeichenginShandongprovinceandCixianinHebeiprovince)from2008to2011wererecruitedinthispopulation-basedscreeningstudy.And2,526subjectsdeclinedtoreceiveendoscopicbiopsyexaminationwithLugol'siodinestaining,while9and815subjectswereexcludedfromliquid-basedcytologyandDNA-ICMtestrespectivelyduetoslidequality.Finally,2,856,5,373and4,567subjectswereenrolledintheanalysisforendoscopicbiopsyexamination,liquid-basedcytologyandDNA-ICMtest,respectively.Sensitivity(SE),specificity(SP),negativepredictivevalues(NPV)andpositivepredictivevalues(PPV)aswellastheir95%confidenceintervals(95%CI)forDNA-ICM,liquid-basedcytologyandthecombinationofthetwomethodswerecalculated.Receiveroperatingcharacteristic(ROC)curveswereappliedtodeterminethecutoffpointofDNA-ICMforesophagealcancer.Results:DNA-ICMresultsweresignificantlycorrelativewithesophagealcancerandprecancerlesions(χ~2=18.016,P<0.001).Thecutoffpointswere5,802,5,803and8,002basedondissimilarpathologicaltypesoflowgradeintraepithelialneoplasia(LGIN),highgradeintraepithelialneoplasia(HGIN),andESCC,respectively,and5,803waschoseninthisstudyconsideringtheSEandSP.TheSE,SP,PPV,NPVofDNA-ICMtest(cutoffpoint5,803)combinedwithliquid-basedcytology[thresholdatypicalsquamouscellsofundeterminedsignificance(ASCUS)]wereseparately72.1%(95%CI:70.3%-73.9%),43.3%(95%CI:41.3%-45.3%),22.8%(95%CI:21.1%-24.5%)and87.0%(95%CI:85.7%-88.3%)forLGIN,85.7%(95%CI:84.3%-87.1%),41.3%(95%CI:39.3%-43.3%),4.6%(95%CI:3.8%-5.4%)and98.9%(95%CI:98.5%-99.3%)forHGIN,and96.0%(95%CI:95.2%-96.8%),40.8%(95%CI:38.8%-42.8%),1.7%(95%CI:1.2%-2.2%)and99.9%