Masitinib Combined with Standard Gemcitabine Chemotherapy In Vitro and In Vivo Studies in Human Pancreatic Tumour Cell Lines and Ectopic Mouse Model 英文参考文献.docVIP

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Masitinib Combined with Standard Gemcitabine Chemotherapy In Vitro and In Vivo Studies in Human Pancreatic Tumour Cell Lines and Ectopic Mouse Model 英文参考文献.doc

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Masitinib Combined with Standard Gemcitabine Chemotherapy In Vitro and In Vivo Studies in Human Pancreatic Tumour Cell Lines and Ectopic Mouse Model 英文参考文献

MasitinibCombinedwithStandardGemcitabine Chemotherapy:InVitroandInVivoStudiesinHuman PancreaticTumourCellLinesandEctopicMouseModel MartineHumbert1,NathalieCaste′ran1,Se′bastienLetard2,3,4,KatiaHanssens1,JuanIovanna5 ,Pascal Finetti4,6,Franc?ois Bertucci4,6,ThomasBader1,ColinD.Mansfield1,AlainMoussy1,OlivierHermine7*, PatriceDubreuil2,3,4 * 1ABScienceSA,Paris,France,2InsermU891,CentredeRechercheenCance′rologiedeMarseille,Signalisation,He′matopo?¨e`seetMe′canismesdel’Oncogene`se,Centrede Re′fe′rence des Mastocytoses, Marseille, France, 3Institut Paoli-Calmettes, Marseille, France, 4Universite′ de la Me′diterrane′e, Marseille, France, 5Inserm U624, Stress Cellulaire,ParcScientifiqueetTechnologiquedeLuminy,Marseille,France,6Inserm,U891,CentredeRechercheenCance′rologiedeMarseille,De′partementd’Oncologie Mole′culaire, De′partement d’Oncologie Me′dicale, Institut Paoli-Calmettes, Marseille, France, 7Ho?pital Necker, Service d’He′matologie, CNRS UMR 8147, Centre de Re′fe′rence desMastocytoses,Universite′ ParisVRene′ Descartes,Paris,France Abstract Background: Tyrosine kinases are attractive targets for pancreatic cancer therapy because several are over-expressed, includingPDGFRa/b,FAK,SrcandLyn.Acriticalroleofmastcellsinthedevelopmentofpancreaticcancerhasalsobeen reported.Masitinibisatyrosinekinaseinhibitorthatselectivelytargetsc-Kit,PDGFRa/b,Lyn,andtoalesserextenttheFAK pathway, without inhibiting kinases of known toxicities. Masitinib is particularly efficient in controlling the proliferation, differentiation and degranulation of mast cells. This study evaluates the therapeutic potential of masitinib in pancreatic cancer,asasingleagentandincombinationwithgemcitabine. Methodology/Findings:Proof-of-conceptstudieswereperformedinvitroonhumanpancreatictumourcelllinesandthen invivousingamousemodelofhumanpancreaticcancer.Molecularmechanismswereinvestigatedviageneexpression profiling. Masitinib as a single agent had no significant antiproliferative activity while the masitini