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ID:49252567
大小:2.23 MB
页数:11页
时间:2020-02-02
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1、HowChronicInflammationcanCauseCancerChronicinflammationlikesunburncansometimescausecancer,buthowithappensremainsunknown.Thisstudyshowsforthefirsttimehowasubstancemadebythebodytopromoteinflammationcancauseanaggressiveformofleukemia.Thisknowledgeenabledtheresear
2、cherstodevelopapossibletreatmentfortheleukemia.gastritisgastriccarcinomaIL-15IL-15IL-15LargeGranularLymphocyteLeukemia(LGLL)LargeGranularLymphocyteLeukemia(LGLL,大颗粒淋巴细胞白血病)chromosomalinstability(CIN)Figure1.ChronicExposuretoIL-15InitiatesRobustExpansionandChro
3、mosomalInstabilityinWTLGLoverexpressionofIL-15asasinglegrowthfactorcaninitiateleukemictransformationofLGLinvivoandtheneoplasticcellsfrompatientswithLGLleukemiahavehigherexpressionofIL-15thantheirnormalLGLcounterparts.adoptivetransferintoSCIDmicewithoutexogenou
4、sIL-15resultedinadramaticincreaseinwhitebloodcell(WBC)count,splenomegaly,anddeathfromfatalleukemiainvivo.multiplecopiesofchromosome15.WeprovidetheevidencethatIL-15alonecanimmortalizeWTLGLinvitrothat,uponadoptivetransferinvivo.Thisoncogeniceffectistheresultoftw
5、odistinctpathwaysbywhichIL-15contributestomalignanttransformation:1,viatheinductionofCINandmarkedaneuploidy;2,viaaninductionofDNAhypermethylation,whichcancontributebothtoCINandtosilencingoftumorsuppressorgenes.Weusedthatinformationtodevelopatreatmentbyinterfer
6、ingwiththeprocess.Theresearchersalsodevelopedatreatmentfortheleukemiathatshowednodiscerniblesideeffectsintheanimalmodel.Wedevelopedaliposomalformulationoftheproteosomeinhibitorbortezomibthatshutsdownthecancer-causingpathway,potentiallycuringthemalignancy.Leuke
7、micmicetreatedwiththeliposomalbortezomibshowed100percentsurvivalat130daysversus100percentmortalityat60-80daysforcontrolanimals.Figure2.InVitroandInVivoTargetingofmiR-29bTranscriptionalRepressionLeukemicmicetreatedwiththeliposomalbortezomibshowed100percentsurvi
8、valat130daysversus100percentmortalityat60-80daysforcontrolanimals.ThankYou
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