Gene Expression Signature Analysis Identifies Vorinostat as a Candidate Therapy for Gastric Cancer 英文参考文献.docVIP

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Gene Expression Signature Analysis Identifies Vorinostat as a Candidate Therapy for Gastric Cancer 英文参考文献.doc

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Gene Expression Signature Analysis Identifies Vorinostat as a Candidate Therapy for Gastric Cancer 英文参考文献

GeneExpressionSignatureAnalysisIdentifiesVorinostat asaCandidateTherapyforGastricCancer Sofie Claerhout1., Jae Yun Lim1,2., Woonyoung Choi3, Yun-Yong Park1, KyoungHyun Kim 4 , Sang-Bae Kim1, Ju-Seog Lee1, Gordon B. Mills1, Jae Yong Cho1,2* 1Division of Cancer Medicine, Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America, 2DepartmentofMedicalOncology,YonseiUniversityCollegeofMedicine,GangnamSeveranceHospital,Seoul,Korea, 3DepartmentofCancerBiology,TheUniversityof TexasMDAndersonCancerCenter,Houston,Texas,UnitedStatesofAmerica, 4DepartmentofVeterinaryPhysiologyandPharmacology,TexasAMUniversity,College Station,Texas,UnitedStatesofAmerica Abstract Background:Gastriccancercontinuestobeoneofthedeadliestcancersintheworldandthereforeidentificationofnew drugstargetingthistypeofcanceristhusofsignificantimportance.Thepurposeofthisstudywastoidentifyandvalidatea therapeuticagentwhichmightimprovetheoutcomesforgastriccancerpatientsinthefuture. Methodology/PrincipalFindings:Usingmicroarraytechnology,wegeneratedageneexpressionprofileofhumangastric cancer–specificgenesfromhumangastriccancertissuesamples.WeusedthisprofileintheBroadInstitute’sConnectivity Mapanalysistoidentifycandidatetherapeuticcompoundsforgastriccancer.Wefoundthehistonedeacetylaseinhibitor vorinostat as the lead compound and thus a potential therapeutic drug for gastric cancer. Vorinostat induced both apoptosis and autophagy in gastric cancer cell lines. Pharmacological and genetic inhibition of autophagy however, increasedthetherapeuticefficacyofvorinostat,indicatingthatacombinationofvorinostatwithautophagyinhibitorsmay therapeutically be more beneficial. Moreover, gene expression analysis of gastric cancer identified a collection of genes (ITGB5, TYMS, MYB, APOC1, CBX5, PLA2G2A, and KIF20A) whose expression was elevated in gastric tumor tissue and downregulatedmorethan2-foldbyvorinostattreatmenting