肿瘤抗血管生成疗法专家讲座.pptx

第九章肿瘤抗血管生成疗法NormalangiogenesisHistoryofAntiangiogenicDrugsRobusttumorgrowthrequiresthepresenceofalocalvascularnetworkthatsuppliesbothoxygenandnutrientstotumorcells.contents第一节、血管生成与肿瘤（1）血管生成普通过程包含五个阶段：调整血管生成原因A调整血管生成因子及其作用B血管壁基质在血管生成中作用C蛋白水解酶系统对于血管生成调整（2）肿瘤与血管生成Mechanismsoftumorneovascularization.(A)Endothelialsproutingisthedominantprocessofvesselgrowth.Luminalendothelialcellsmigratethroughthevesselbasementmembraneintotheunderlyingextracellularmatrix,developinganelongated'sprouting'morphology.(B)Vasculogenicmimicryisthedevelopmentofmicrovascularchannelsbyaggressivetumorcells.(C)Vesselco-optioninvolvestheuseofthepre-existingvasculatureinthehosttissue.(D)Theprocessoftumorneovascularization,involvingthereleaseofproangiogenicfactors(e.g.VEGF)bytumorcellstocauseendothelialactivation,bloodvesselgrowth,andsubsequenttumorexpansion.肿瘤新生血管形成过程肿瘤新生血管形态结构和功效特点Figure13.33TheBiologyofCancer(©GarlandScience)（3）肿瘤血管生成与肿瘤发生、生长和转移侵袭和转移第二节、肿瘤血管生成评定VEGF检测方法(microvesseldensity，MVD)Vesselandmicrovesseldistributionsofthetransfectedmelanomatumors.Toevaluatetheendothelialcellcontentoftumors,thefixed,embeddedtumortissuesweresectionedandstainedforimmunoreactiveCD31incontroltumors(A)and(B)andIP-10-transfectedmelanomatumors(C)and(D).(E)MicrovesseldensitywasdigitallymeasuredfromfiverandomfieldsusingtheImage-ProPlusprogram(MediaCybernetics,LP).MicrovesseldensityisreducedinthyroidtumorscontainingPPFP.ImmunohistochemicalanalysisofFA(A,B)andFTC(C,D)demonstrateda2.3-and2.5-folddecrease(P<0.005andP<0.05,respectively)inmicrovesseldensityasmeasuredbyCD31staininginadenomasandcarcinomascontainingPPFP,respectively(B).第三节、血管生成抑制剂研究及临床应用现实状况抑制肿瘤血管生成策略(1)直接抑制内皮细胞增殖内皮抑素EndostatinEndostatin发觉O’reillyMS,etal.Cell1997;88:277-285.内皮抑素作用机理我国首家开发endostatin药品山东麦得津生物工程股份有限企业恩度TM(Endostar)Ⅲ期临床试验Ⅲ期临床试验Ⅲ期临床试验年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药品FDAapproveddrugsGefitinib(Iressa®)MechanismofActionAvastin(bevacizumab)AvastincausesregressionoftumourvasculatureAvastinnormalisesexistingtumourvasculatureSumma