胃癌相關(guān)分子遺傳學(xué)特征及治療的研究.pdf

1、分類號分類號：R735.2R735.2密級密級：不保密不保密UDCUDC：610610學(xué)校代碼學(xué)校代碼：1106511065博士專業(yè)學(xué)位論文胃癌相關(guān)分子遺傳學(xué)特征及治療的研究胃癌相關(guān)分子遺傳學(xué)特征及治療的研究高峰玉指導(dǎo)教師宣世英教授學(xué)位類別臨床醫(yī)學(xué)博士專業(yè)領(lǐng)域內(nèi)科學(xué)（消化系?。┐疝q日期2015年6月5日答辯委員會主席陸倫根Theresearchofgastriccancermoleculargeicsacteristicstherape

2、uticAbstractBackgroundobjectives:Gastriccancerisoneofthemostfrequentdigestivemalignanttuminthewldwhichcouldthreatenhumanshealth.itsincidencemtalityhavebeenamongthehighestinthewldmalignanttum.OfcourseGastriccancerisstillo

3、neofthemajthreatstohumanhealthbecauseitislowinearlydiagnosisthebesttreatmentopptunityhasbeendelayed.Sodetectingsomegenestoimprovetheearlydiagnosisrateofgastriccancertakingactivetreatmenttoreducetheincidenceofgastriccance

4、risparticularlyimptant.MicrNAsareaclassofhighlyconservedendogenousnoncodingsmallRNAgenesthelengthofwhichisabout22nucleotides.Itplaysanimptantroleintheprogressofgastriccancerthroughregulatingoncogenestumsuppressgenesactin

5、gonthetargetgenesassociatedwithapoptosisproliferation.Helicobacterpyliinfectionisthemostimptantpathogenicfactinthedevelopmentofgastriccancerwhichhasbeenconfirmedbyclinicaltrialinvestigationofepidemiology.Therefeeradicati

6、onofHelicobacterpyliisthekeytoreducetheincidenceofgastriccancer.OurexperimentistoexpletheexpressionroleofmiR132ingastriccancer.observetheeffectofclostridiumbutyricuminHelicobacterpylitherapy.Methods:Inthepresentstudythee

7、xpressionlevelsofmiR132wereanalyzedingastriccancersamplesbyquantitativerealtimereversetranasepolymerasechainreaction.Besidescellviabilityproliferationinvasionabilitiesweredeterminedintwogastriccancercelllines（NCIN87、MGC8

8、03）transfectedwithmiR132mimicsantisenseoligos.itstargetgenewasidentifiedatthesametime.InthisstudywealsoobservetheeffectofHelicobacterpylieradicationtherapyinwhichwecombinedclostridiumbutyricumwithstardtripletherapy.Resul

9、ts:1.MiR132expressionlevelswassignificantlyincreasedingastriccancertissuesthanintheirmatchedadjacentnoncanceroustissues.2.MiR132maypromotegastriccancercellproliferationinvasion.3.Atthemolecularlevelourdatademonstratedtha

10、tmiR132couldinhibitproteinlevelsofRetinoblastoma1(RB1)throughtargetingits3’untranslatedregionmiR132directlytargetstheRB1ingastriccancercells.4.RB1overexpressionblockedtheproliferativerolesofmiR132.5.Clostridiumbutyricumc

11、ombinededwithstardtripletherapycanimprovetheeradicationratereducetheincidenceofadversereactions.Conclusions:1.Mir132mightbeapotentialnoveldiagnostictherapeutictargetofgastriccancer.2.Clostridiumbutyricumwashelpfultoimpro

12、vetheeradicationrateofHelicobacterpylitherapymayreducetheincidenceofgastriccancer.Postgraduatestudent:FengyuGao(internalmedicine)DirectedbyProf.ShiyingXuanKeywds:gastriccancermicrNAMiR132；HelicobacterpyliClostridiumbutyr