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PartialMolecularPathogenesisin
BladderCarcinoma夏阳阳2016-7-13contentEpidemicsGradeandstageClassificationbasedongeneticcharactericsSomepathwaysAristolochicAcid(AA)LindseyA.Torre,MSPH;FreddieBray,PhD,etal.Globalcancerstatistics,2012.CACANCERJCLIN2015;65:87–108EstimatednewcasesEstimateddeath74769STAGEPrimaryTumorT0NoevidenceoftumorTaNoninvasivepapillaryurothelialcarcinomaTisUrothelialcarcinomainsituT1TumorinvadeslaminapropriaT2Tumorinvadessuperficial(2a,innerhalf)ordeep(2b,outerhalf)muscularispropriaT3Tumorinvadesmicroscopically(3a)ormacroscopically(3b)perivesicaltissueT4Tumorinvadesadjacentorgans(4a,prostaticstroma,seminalvesicles,uterus,vagina)orpelvicorabdominalwall(4b)RegionalLymphNodesN0NolymphnodemetastasisN1SinglelymphnodemetastasisinthetruepelvisN2MultiplelymphnodemetastasesinthetruepelvisN3LymphnodemetastasistothecommoniliaclymphnodesDistantMetastasisM0NodistantmetastasisM1DistantmetastasisStageGroupingsStage0TaN0M0orTisN0M0StageIT1N0M0StageIIT2N0M0StageIIIT3N0M0orT4aN0M0StageIVT4bN0M0AnyT,N1-3,AnyMAnyT,AnyN,M1EdgeSB,ByrdDR,ComptonCC,FritzAG,GreeneFL,TrottiA.Urinarybladder.In:EdgeSB,ByrdDR,ComptonCC,FritzAG,GreeneFL,TrottiA,eds.AJCCCancerStagingManual.7thed.NewYork,NY:Springer;2010:497–505.non-muscleinvasivebladdercancer(NMIBC)muscleinvasivebladdercancer(MIBC)TaTisT1T2T3T4GRADE1973cellularanaplasia2004architecturalandcytologicalatypiaPUNLMP=papillaryurothelialneoplasmoflowmalignantpotentialAshishMKamat,NoahMHahn,JasonAEfstathiouetal.Bladdercancer,2016.lancetS0140-6736(16)30512-8
.ClassificationBasedonGeneticCharacteristicspapillaryNon-papillaryColinP.N.Dinney,DinneyCP,McConkeyDJ,MillikanRE,etal.Focusonbladdercancer.CancerCell2004;6:111–1660%:alterationninvolvesexons5–11ofp53andthelossofRBgenefunction
20%:synchronouslossofthetandemlylinkedCDKN2aandARF
20%:alterationsofp53inexons1–4followedbylossofCDKN2aandARFfunctionBasal-likeandLuminalBasalMIBCssharedbiomarkerswithbasalbreastcancersandwerecharacterizedbyp53activation,squamousdifferentiation,andmoreaggressivediseaseatpresentation.LuminalMIBCscontainedfeaturesofactivePPARγandestrogenreceptor(ER)transcriptionandwereenrichedwithactivatingFGFR3mutationsandpotentiallyFGFRinhibitorsensitivity.CancerGenomeAtlasResearchNetwork.Comprehensivemolecularcharacterizationofurothelialbladdercarcinoma.Nature2014;507:315–221.BarskiA,CuddapahS,CuiK,RohTY,SchonesDE,WangZ,WeiG,ChepelevI,ZhaoK(May2007)."High-resolutionprofilingofhistonemethylationsinthehumangenome".Cell129(4):823–37.doi:10.1016/j.cell.2007.05.009.PMID17512414.
2.RosenfeldJA,WangZ,SchonesDE,ZhaoK,DeSalleR,ZhangMQ(2009).
"Determinationofenrichedhistonemodificationsinnon-genicportionsofthehumangenome".
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3.KochCM,AndrewsRM,FlicekP,DillonSC,KaraözU,ClellandGK,WilcoxS,BeareDM,FowlerJC,CouttetP,JamesKD,LefebvreGC,BruceAW,DoveyOM,EllisPD,DhamiP,LangfordCF,WengZ,BirneyE,CarterNP,VetrieD,DunhamI(Jun2007).
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17567990.ChromosomalAlterationsThemostfrequentobservedcopynumberaberrationsinUCareonchromosomes1,8,9,10,11,13,and14.Chromosome9alterationsaretheearliestgeneticalterationsinbothofthedescribeddivergentpathwaysofBCdevelopment[1]1.MingZhao,Xiang-LeiHe,Xiao-DongTeng,Understandingthemolecularpathogenesisandprognosticsofbladdercancer:anoverviewStructuralrearrangementsandviralintegrationTheCancerGenomeAtlasResearchNetwork,ComprehensiveMolecularCharacterizationofUrothelialBladderCarcinomaSomeexamplesforchromosomalalterrationAristolochicAcid(AA):acarcinogenforUTUCOverview:Aristolochicacid(AA)isanitrophenanthrenecarboxylicacidfoundinallmembersofthegenusAristolochiausedformedicalpurposesformorethan2000yearsnephrotoxicityandcarcinogenicityassociatedwiththeuseoftheseplantscametolightwhenAristolochiafangchi,administeredto1800healthyBelgianwomenaspartofaweightreductionregimen,resultedinmorethan100casesofchronictubulointerstitialdiseaseprogressingtoend-stagerenalfailure.ManyoftheaffectedwomendevelopedneoplasticchangesintheupperurinarytractAnalysisofTP53mutationrevealsAAasaenvironmentalcarcinogenHollsteinM,MoriyaM,GrollmanAP,OlivierM.AnalysisofTP53mutationspectrarevealsthefingerprintofthepotentenvironmentalcarcinogen,aristolochicacid.MutatRes.201310.1016/j.mrrev.2013.02.00319.MarieSTIBO
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