肝切除术后伴高危因素联合索拉非尼治疗肝癌中文图.ppt

*抑制RAF/MEK/ERK信号传导通路中的RAF激酶，阻断肿瘤细胞增殖抑制血管内皮细胞及周细胞的VEGFR-2和PDGFR-β酪氨酸激酶，控制肿瘤血管生成索拉非尼抑制肿瘤细胞增殖、凋亡和血管生成红X：索拉非尼抑制点黑色箭头/线：建立的通路粉红色箭头/线：索拉非尼影响的通路肿瘤细胞中，索拉非尼通过抑制RAS-RAS-MEK-ERK通路，导致细胞凋亡索拉非尼也通过RAF/MEK/ERK通路导致细胞凋亡，包括抑制eIF4E，Mcl1表达下调在血管内皮细胞中，索拉非尼抑制酪氨酸激酶，包括VEGF和PDGFR**综上所述：姑息性手术有一定的疗效，术后联合局部治疗可以增进疗效，然而局部治疗的联合无法解决全身问题，索拉非尼的双重抗肿瘤作用与手术完美结合抑制肿瘤复发*****IsaiahJ.Fidler,etal.Thepathogenesisofcancermetastasis:the‘seedandsoil’hypothesisrevisited.NatureReviewsCancer2003;3:453-458.Researchershavebeenstudyingmetastasisformorethan100years,andonlyrecentlyhavewegainedinsightintothemechanismsbywhichmetastaticcellsarisefromprimarytumoursandthereasonsthatcertaintumourtypestendtometastasizetospecificorgans.StephenPaget’s1889proposalthatmetastasisdependsoncross-talkbetweenselectedcancercells(the‘seeds’)andspecificorganmicroenvironments(the‘soil’)stillholdsforthtoday.Itisnowknownthatthepotentialofatumourcelltometastasizedependsonitsinteractionswiththehomeostaticfactorsthatpromotetumourcellgrowth,survival,angiogenesis,invasionandmetastasis.Howhasthisfielddevelopedoverthepastcentury,andwhatmajorbreakthroughsaremostlikelytoleadtoeffectivetherapeuticapproaches?***SorafenibBlockstheRAF/MEK/ERKPathway,InhibitsTumorAngiogenesis,andInducesTumorCellApoptosisinHepatocellularCarcinomaModelPLC/PRF/5AngiogenesisandsignalingthroughtheRAF/mitogen-activatedprotein/extracellularsignal-regulatedkinase(ERK)kinase(MEK)/ERKcascadehavebeenreportedtoplayimportantrolesinthedevelopmentofhepatocellularcarcinomas(HCC).Sorafenib(BAY43-9006,Nexavar)isamultikinaseinhibitorwithactivityagainstRafkinaseandseveralreceptortyrosinekinases,includingvascularendothelialgrowthfactorreceptor2(VEGFR2),platelet-derivedgrowthfactorreceptor(PDGFR),FLT3,Ret,andc-Kit.Inthisstudy,weinvestigatedthein