以hdac为靶点干预消化道肿瘤的初步分析

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1、第三军医大学硕士学位论文PreliminarystudyofinterventionofGastrointestinalcancerwithHDACastargetAbstractBackground:Gastrointestinalcancer(GIC)isthesecond-leadingcauseofcancerdeathintheworld,withabout50,000patientsdyingeachyearasaresultofmetastaticdiseasethatisrefractorytosystemictherapy.Althoughtherearenumerous

2、studieshavebeenfocusedontheinitiationandtheprogressionofgastrointestinalcancer,theunderlyingmechanismremainslargelyunrevealed.AbetterunderstandingofthemechanismofGICinitiationandprogressionisimperativeforthedevelopmentofmoreeffectivetherapeuticapproachesthatcanbenefitpatientswithCRC.Orderlytranscr

3、iptionalregulationiscriticalformaintainingthenormalfunctionofsomaticcells.Thechromatinstructurechangeisanimportantmechanismofgeneexpressionregulationineukaryoticcells,andthecellswithdisorderofchromatinstructureregulationwilllosetheirgrowthcontrolandresultinamalignanttransformation.Ithasbeendemonst

4、ratedthathistoneacetylase(HAT)andhistonedeacetylase(HDAC)canchangethechromatinstructure.Histoneplaysimportantrolesnotonlytobeacompositionbutalsotokeepthedynamicbalanceofchromatin.Changesofthehistoneacetylationstatusofnucleosomeswillconsequentlyaffecttheactivitiesoftheirspecialtranscriptionfactors,

5、andthereforechangetheexpressionsofrelatedgenes.HistoneacetylationstateiscoordinatelyregulatedbyHATsandHDACs,andinvolvedinmultipleprocesseslikeDNAdamagerepair,chromosomeectopic,transcriptionalregulation,genesilencing,celldifferentiationandproliferation,cellcycle,cellapoptosis,andsoon.Increasingevid

6、encehaveshownthatthedysfunctionofHATsandHDACspivotallycontributetotheinitiationandprogressionofcancercell.PrevioustargetedtherapieshavenotdramaticallyimprovedclinicaloutcomesofpatientswithGIC.GiventhecriticalrolesofHATsandHDACsincancerpathogenesis,potentialroleofHATsandHDACsasnewtargetsofGICtherap

7、ymayimplicatedinthefuture.3第三军医大学硕士学位论文PARTONETheeffectsofHDAC1knockdownoncellgrowthandradiosensitivityofEC109cellsObjectives：TofurtherexploretheeffectofHDAC1incancerpathogenesisandtheunderlyingmolecularmechanism