《粘附分子抑制剂精品文稿.ppt》由会员分享，可在线阅读，更多相关《粘附分子抑制剂精品文稿.ppt（20页珍藏版）》请在taowenge.com淘文阁网|工程机械CAD图纸|机械工程制图|CAD装配图下载|SolidWorks_CaTia_CAD_UG_PROE_设计图分享下载上搜索。
1、粘附分子抑制剂第1页，本讲稿共20页background knowledgeNatalizumab：a recombinant humanized IgG4 monoclonal antibody,which binds integrin-a4,in MM;integrin:cell surface receptors that mediate both cell-cell and cell-extra cellular matrix adhesion;fibronectin:strong adhesive components for MM cells via interaction of
2、a variety of integrins including integrin-a4。第2页，本讲稿共20页MM细胞的粘附过程骨髓基质细胞促进MM细胞增殖整合蛋白MM 细胞第3页，本讲稿共20页SummaryIntegrin-a4 expression in the MM bone marrow microenvironment；Natalizumab inhibits MM cell adhesion to fibronectin,endothelial cells；Natalizumab inhibits MM cell adhesion to BMSCsas well as MM c
3、ell proliferation triggered by MM-BMSC adhesion；Natalizumab inhibits MM-BMSC-induced secretion of VEGF and angiogenesis；Natalizumab inhibits VEGF-and IGF-1-triggered MM cell migration on fibronectin；Natalizumab inhibits MM cell growth in a murine model of MMNatalizumab sensitizes MM cells attached t
4、o BMSCs and endothelial cells to bortezomib.第4页，本讲稿共20页NO.1 Integrin-a4 expression in the MMbone marrow microenvironmentAll of theMM cell lines expressed integrin-a4；ITGA4 was significantly upregulated in plasma tumour cells derived from MM patients versus plasma cells from healthy donors；neither en
5、dothelial cells nor primary BMSCs or BMSC cell lines expressed integrin-a4。第5页，本讲稿共20页NO.2 Natalizumab inhibits MM cell adhesion to fibronectin,and endothelial cells第6页，本讲稿共20页nodulus：1.Pretreatment with Natalizumab inhibits MM cell adhesion to fibronectin(A)or endothelial cells(B);2.pretreatment wi
6、th Natalizumab decreased K562a4,but not K562,cell adhesion to fibronectin(C);3.Natalizumab disrupted the binding of already adherent MM cells(D-F).第7页，本讲稿共20页NO.3 Natalizumab inhibits MM cell adhesion to BMSCs as well as MM cell proliferation triggered by MM-BMSC adhesion第8页，本讲稿共20页nodulus：1.Nataliz
7、umab inhibited adhesion to BMSCs of non-binding MM(A);2.Natalizumab also inhibited adhesion to BMSCs of already adherent MM(B);3.increased MM cell proliferation triggered by MM-BMSC adhesion was inhibited by Natalizumab(C).第9页，本讲稿共20页NO.4 Natalizumab inhibits MM-BMSC-induced secretion of VEGF and an
8、giogenesis第10页，本讲稿共20页nodulus:1.Natalizumab significantly inhibited MM-BMSC-triggered increases of VEGF secretion(A);2.endothelial cell tubule formation triggered by supernatants derived from Natalizumab-,treated MM-BMSC co-cultures(5 h),was markedly inhibited(B-C).第11页，本讲稿共20页NO.5 Natalizumab inhib
9、its VEGF-and IGF-1-triggered MM cell migration on fibronectin第12页，本讲稿共20页nodulus:1.Natalizumab abrogates both VEGF-as well as IGF-1-triggered MM(MM.1S,OPM2)cell migration on fibronectin(A,B)；2.Natalizumab abrogates phosphorylation of both PKC and integrin-a4 which induced by costimulation with eithe
10、r IGF-1 or VEGF and fibronectin（C,D）.第13页，本讲稿共20页NO.6 Natalizumab inhibits MM cell growth in a murine model of MM第14页，本讲稿共20页nodulus:1.the levels of ShuIL-6R in MM is downregulated which is treated buy Natalizumab(A);2.Natalizumab increased animal survival(B);3.Natalizumab also downregulated express
11、ion of human VEGF and Ki67 and H&E(C);4.tumour angiogenesis of MM which is pretreated by Nab is lower than those non-treated by it(D).第15页，本讲稿共20页NO.7 Natalizumab sensitizes MM cells attached to BMSCs and endothelial cells to bortezomib第16页，本讲稿共20页nodulus:Natalizumab synergistically enhanced sensiti
12、vity of tumour cells to bortezomib in both MM-BMSC and MM-EC co-cultures as well as to dexamethasone(this experiment didnt show)第17页，本讲稿共20页conclusion inhibite adhesion of MM cells to BMSC or HUVECNabNabblock the proliferative effect of MMchemosensitize MM cells to bortezomibblock the angiogenesis i
13、nduced by VEGFinhibite tumour growth,VEGF secretion,and angiogenesis in murine model of human MM in the human BM microenvironmentBlock MM cell migration第18页，本讲稿共20页Discussionintegrin-a4 may be an attractive target for the treatment of the disease at its early stages;a potential therapeutic role for the SAM inhibitor Natalizumab which specifically targets integrin-a4 in MM;whether maintenance therapy with Natalizumab in combination with low dose bortezomib or dexamethasone after conventional therapies prevents or delays the progression of minimal residual disease.第19页，本讲稿共20页第20页，本讲稿共20页