中国医科大学病理学.ppt

Section8.Etiologyandpathogenesisoftumor,8.1Molecularbasisofoncogenesis,8.1.1Oncogene1.Protooncogene,oncogeneandproducts(1)Protooncogene:cellulargenesthatpromotenormalcellgrowthanddifferentiation,existinnormalcells,intheformofinactivity.(2)Oncogene:derivedfromprotooncogenepromoteabnormalgrowth.,(3)ModeofprotooncogenesactivationPointmutationChromosomalrearrangementGeneamplificationpromoterinsertion,(4)Productsandfunctionsofprotooncogenes,Growthfactors:PDGF,FGF,EGFGrowthfactorreceptorsSignal-transducingproteins:rasNuclearregulatoryproteins:mycCellcycleregulatoryproteins:cyclins,8.1.2Tumorsuppressorgene,1.Concept:cellulargenesthatexistinnormalcellsinhibitnormalgrowthandcausecellstomalignanttransformwhentheybecomeinactive.2.Examples:Rb,p53,P16,TGF-,BRCA-1,BRCA-23.mechanism:allelemutation,deletion,methylation,8.1.3GenesthatregulateapoptosisandDNArepair,GenesthatregulateapoptosisBcl(B-celllymphoma)family:Bcl-2:inhibitapoptosisBax:induceapoptosis2.GenesthatregulateDNArepair:,8.1.4Telomeres,telomeraseandcancer,1.Telomeresshortingisbelievedtobeaclockthatcountscelldivision,isatumor-suppressivemechanism.2.Telomerase:SustainthefunctionoftelomeresAbsentfrommostsomaticcellIncreasedactivityofittumor,8.1.5Molecularbasisofmultistepcarcinogenesis,8.2Environmentalfactorsandtheirmechanism,8.2.1CheminalcarcinogenicagentsIndirect-actingagentPolycyclichydrocarbons:infossilfuelorcombustionoftabaccoinsmoking,relatetothedevelopmentofskin,lung,stomachcarcinoma(2)Aromaticaminesandazodyes:bladder,hepatocellularcarcinoma(3)Aflatoxin:potenthepatocarcinogen(4)Nitrosamines:lung,gastric,esophagus,2.Direct-actingagents(1)Alkylatingandacylatingagents:anticancerdrugscyclophosphamide(2)Othersarsenicskincarcinomachromiumlungcarcinomacadmiumprostatecarcinomanickellungcarcinoma,8.2.2Physicalcarcinogenicfactors,1.Ionizingradiation:X-ray,-rayrelatedtoleukemia,carcinomaofskin,lung,breast,colon.2.UV:skincarcinoma3.Others:asbestosmesotheliomaartificialmammarycarcinoma,8.2.3Biologiccarcigenicagents,1.RNAvirus:Transduction/insertionalmutagenesisHTLV-1:humanTcellleukemia/lymphoma2.DNAvirus:(1)HPV:cervicalsquamouscellcarcinoma(2)Epstein-Barrvirus:nasopharyngealcarcinoma(3)HBV:hepatocytecarcinoma3.Helicobacterpylori:chronicgastritis,Blymphomaofstomach,8.3Internalfactorsanditsmechanism,8.3.1Inheritedpredispositiontocarcinogens1.Inheritedcancersyndrome(Autosomaldominant)Familialretinoblastoma2.Autosomalrecessivesyndromes:Bloomsyndrome,fanconianemia3.Familialcancer:breast,ovary,colon,8.3.2Tumorimmunity,1.Tumorantigen:TumorspecificAg:onlyinneoplasticTumorassociatedAg:CEA,AFP2.Antitumorimmunity:mainlycellimmunityTcell:lymphotoxinNKcell,Macrophage:ADCC3.Immunesurveilance:Immunodificienthost/immunosuppressed4.Immunotherapy:stimulatetheendogenousreaction,increasethefunctionofantitumor,复习思考题1.比较良、恶性肿瘤的区别？2.高分化鳞癌的结构特点？3.何谓实性癌？简述其病理特点？4.异型性、分化程度及与肿瘤良