肿瘤抗血管生成疗法课件.pptVIP

;Normalangiogenesis;;;HistoryofAntiangiogenicDrugs;;Robusttumorgrowthrequiresthepresenceofalocalvascularnetworkthatsuppliesbothoxygenandnutrientstotumorcells.;contents;第一节、血管生成与肿瘤

（1）血管生成的一般过程;;

;;

;包括五个阶段：;调节血管生成的因素;A调节血管生成的因子及其作用;;;

;B血管壁基质在血管生成中的作用;C蛋白水解酶系统对于血管生成的调节;（2）肿瘤与血管生成;;;;;;;;Mechanismsoftumorneovascularization.

(A)Endothelialsproutingisthedominantprocessofvesselgrowth.Luminalendothelialcellsmigratethroughthevesselbasementmembraneintotheunderlyingextracellularmatrix,developinganelongatedsproutingmorphology.(B)Vasculogenicmimicryisthedevelopmentofmicrovascularchannelsbyaggressivetumorcells.(C)Vesselco-optioninvolvestheuseofthepre-existingvasculatureinthehosttissue.(D)Theprocessoftumorneovascularization,involvingthereleaseofproangiogenicfactors(e.g.VEGF)bytumorcellstocauseendothelialactivation,bloodvesselgrowth,andsubsequenttumorexpansion.;肿瘤新生血管形成的过程;肿瘤新生血管的形态结构和功能特点;

;Figure13.33TheBiologyofCancer(?GarlandScience2007);;（3）肿瘤血管生成与肿瘤的发生、生长和转移;;侵袭和转移;第二节、肿瘤血管生成的评估;VEGF的检测方法;(microvesseldensity，MVD);Vesselandmicrovesseldistributionsofthetransfectedmelanomatumors.Toevaluatetheendothelialcellcontentoftumors,thefixed,embeddedtumortissuesweresectionedandstainedforimmunoreactiveCD31incontroltumors(A)and(B)andIP-10-transfectedmelanomatumors(C)and(D).(E)MicrovesseldensitywasdigitallymeasuredfromfiverandomfieldsusingtheImage-ProPlusprogram(MediaCybernetics,LP).;ReddiHetal.GenesCancer2010;1:480-492;第三节、血管生成抑制剂研究及临床应用现状;抑制肿瘤血管生成的策略;;(1)直接抑制内皮细胞增殖;内皮抑素Endostatin;Endostatin的发现;O’reillyMS,etal.Cell1997;88:277-285.;;内皮抑素的作用机理;我国首家开发endostatin药物

山东麦得津生物工程股份有限公司;恩度TM(Endostar);Ⅲ期临床试验;Ⅲ期临床试验;Ⅲ期临床试验;2006年的第一版非小细胞肺癌临床实践指南（中国版）已将恩度联合化疗列入了一线标准化治疗方案

;(2)阻断血管生成因子活性的药物;FDAapproveddrugs;Gefitinib(Iressa?)

MechanismofAction;;Avastin(bevacizumab);Avastincausesregr