病毒感染与肿瘤发生

肿 病因学的提致肿瘤机Epstein- 与Burkitt淋巴瘤、鼻咽 与宫颈DiscussionofViral复旦FIST暑期课(2013,2014,2015,Infectious 《ViralOncology:BasicScienceandClinicalApplications》KhaliliK& ngKT.2009，SBN-《PrinciplesandPracticeofCancerInfectiousDiseases》,SafdarA2011ISBN:978-1-教师风

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医医学

S.UNevada

学2总学日星节上课内授课教—11-传染肿瘤学概二11-性机理1（小）三11-性机理2（大）四11-性机理）五11-性机理4（）—11-性机理5（动）二11-细菌机三11-环境与病原生物机四11-传染肿瘤免疫治五11-传染肿瘤靶向治周东—11-专题讨论二11-专题讨论SuhbashWhyOpen“IO”Asmallbutsignificantproportionhumancancersworldwidearecausedmechanismsthatorparasites(~15%).The

es, contributorsareDNA (Evidencefromthedetectionofesincancerpatientsandpartlyfrom WhyOpen“IO” esthatdirectlycausecancerineitherexperimentalanimalsorhumansUnderstandtheformationofcurrentconceptsofcancerbiologyRecognitionoftheetiologyofsomehumancancers.WhyOpen“IO”Helpbasicresearchstudentsinmedicalmicrobiologytounderstandwhat’sDriveclinicalstudentsintherapeuticOncologytothinkmoreaboutInfectiousPathogensnotjustCANCER.WhyStudyInfectionPrevention–

identifyprecursorsanti-virals,ProvidesinsightsintoImportantproblemlargeworldwideburdenofWhatisinaCancercellsmakeupasmall ofaTumors>90%stromalLargeamountofextra-cellularmatrixmaterial.1250mgsProstaticProportionsofCancerscausedbyMajorRiskFactors

(Source:CancerAtlas,contributionofGlobalCancerincidenceby(Source:GlobalCancerStatistics,ChangesincellthatareattherootsofcancerGeneticandepigenetic (Proto-oncogene,tumorsuppressorgene,mutatorgene)Ifyou’reinfected,doesthismeanthatyouwillgetcancer?esdidnotspecificallyevolvewiththeneedtocausecancer-theysimplyhavesimilar(butdistinct)needsDevelopmentoftumorsalmostalways tions esareusuallynotcompletecarcinogensinhumancancers; establishlong-termpersistentinfectionsinhuman,withcanceranaccidentalsideofviralreplicationstrategy.Thebest-characterizedmechanismsoftransformationby Permanentactivationofmitoticsignaltransductioncascades;DisruptionofthecircuitsthatregulatescellHOSTVIRAL

CellSecreteApoptosis,疾病的发生、发肿瘤发生？ViralEllermann&Bang(1905,Denmark):ChickenRous(1911,USA):Rousa（用滤液成功地诱发了 瘤—1966Nobel医学和生理学

---〉淋巴Shope(1933,Denmark):诱发野兔状瘤-浸(tre&Temin1970RSV研究---〉1975NobelEpstein&Barr(1964): ‹‹30-40%HumanTimelineofAdvancesonTumorJavier,R.T.etal.CancerResNobelPrizeWinnersinTumorIdentificationoffirstretroviraloncogenefromRSV---furtherbeaddressedin“RNATumor”section.How esContributetoIntegrationsthatcauseactivationorinactivationofoncogenesortumorsuppressors(e.g.RNA Expressionofgenesthatalterkeysignaltransductionpathways-thisisourfocusChronicactivationofinfl Why escauseesandcancercellshavesimilarProliferationCelldeathModulationofimmuneInductionofMetastasis(tumor)/cellmigration( Majorhuman SmallDNA BHuman Merkelcell (MCV, esEpstein Kaposi’sa HumanT-cell 1SmallLargeesandHPV16,18,31,33, CervicalHepatitisB&C Hepatocellular AdultTcellEpstein-Barr(HHV- Burkitt’sHodgkin’sDiseaseNasopharyngealCarcinomaGastricCarcinoma?Kaposia-associatedherpes(KSHV,HHV-8)

Kaposi’sa,PEL,EvidenceEvidenceforclassifyinga Presenceofpartofviralgenomeintumorsandexpressionofsomeviralgenes.InvitroinfectionofcellsleadstoGrowthinlowserum(reducedgrowthfactorGrowthinsoftagar(anchorageindependent Identificationofviralgenesthattransformcellsinculture InfectionofanimalmodelsystemresultsinNopossibleforhumanVaccinationpreventstumor2001NobelPrize（Physiology-Therearecheckpointsduringwhichthecell“checks”whethertocontinueprogressingthroughthecellcycle.HowHowestransform infectionprovidesa“hit”towardsthegenesisofcancer.Actasa Othercofactors(genetic,immunological,orenvironmental)maybeneededfordevelopmentofcancer Celltransformationispaniedbythepersistenceofallorpartoftheviralgenomeandcontinualexpressionofalimitednumberofviral Viraloncogenesareexpressedthatalternormalcellulargeneexpressionandsignaltransductionpathways.GeneralizationGeneralizationaboutViralRNAesactivateDNAesnegateTumorLMP1isaOneofseveralEBVgenesimplicatedinimmortalizationofBBCellProliferation:Increaseexpressionofadhesionmolecules,CD23,CD40,IL-6,IL-10,etc. Inhibitsapoptosis: Bcl-2,A20,Mcl-1LMP-1mimicsconstitutivelyformofCD40inBThorley-Lawson,NatureRevImmunol,HPV16E7HCVNS5AHBVpXKSHVLANA1

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