病毒感染與腫瘤發(fā)生

腫 病因?qū)W的提致腫瘤機(jī)Epstein- 與Burkitt淋巴瘤、鼻咽 與宮頸DiscussionofViral復(fù)旦FIST暑期課(2013,2014,2015,Infectious 《ViralOncology:BasicScienceandClinicalApplications》KhaliliK& ngKT.2009，SBN-《PrinciplesandPracticeofCancerInfectiousDiseases》,SafdarA2011ISBN:978-1-教師風(fēng)

所

所所

醫(yī)醫(yī)學(xué)

S.UNevada

學(xué)2總學(xué)日星節(jié)上課內(nèi)授課教—11-傳染腫瘤學(xué)概二11-性機(jī)理1（?。┤?1-性機(jī)理2（大）四11-性機(jī)理）五11-性機(jī)理4（）—11-性機(jī)理5（動(dòng)）二11-細(xì)菌機(jī)三11-環(huán)境與病原生物機(jī)四11-傳染腫瘤免疫治五11-傳染腫瘤靶向治周東—11-專(zhuān)題討論二11-專(zhuān)題討論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,疾病的發(fā)生、發(fā)腫瘤發(fā)生？ViralEllermann&Bang(1905,Denmark):ChickenRous(1911,USA):Rousa（用濾液成功地誘發(fā)了 瘤—1966Nobel醫(yī)學(xué)和生理學(xué)

---〉淋巴Shope(1933,Denmark):誘發(fā)野兔狀瘤-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

HPV16E6HCVNS5AHBVpXKSHVLAN