肿瘤的生物学特性 23页

4\n物质代谢及酶的变化肿瘤细胞的分化肿瘤细胞的生长♦肿瘤细胞扩散的过程机制♦4\n肿瘤侵袭和转移相关基因4\n4\n物质代谢及酶的变化核酸代谢核酸增多是肿瘤迅速生长的物质基础ADNA拓扑异构酶端粒酶\n物质代谢及酶的变化核酸代谢DNA拓扑异构酶存在于细胞核内的一类酶，他们能够催化DNA链的断裂和结合，从而控制DNA的拓扑状态。•DNA拓扑异构酶通过形成短暂的单链裂解-结合循环,7\n物质代谢及酶的变化催化盛复制的拓扑异构状态的变化7\n—TypeIBkDgCTop3cx.112Topap97Tc>p1lOOTopinrt70CTopZcx.170(X2)Top2p180(x2)P-YALk.B±1TopoITopoIIIGyraseTypeIIA!：・7t-aK8P-YALk9874,GyrA97(X2)।GyrK90Cx2)S'士2士NFItT81TopiTopimlEllipticineAzatoxlnQuinolonesIsoflavonesinci^no'；ARC-111Etopo%iderpScrpThrpSerp5c「一$771393147014741525^XDNABinding/DMACleavageTopoismerase\nFig,(1).PrimarydomainstructureofthetopoisomeraseIlaandtopoisomeraseUpisozymes.ThehomologousN-tcnniiialATPascregionandcentralcatalyticcoreregionsofthetwoenzymesarcdepictedbysimilarlyfilledboxes,whereasthenon-homologusC-terminalregulatorydomainsaredepictedbyboxeswithdifferentstripes.NLSmdicatcsnuclearlocalizationsignal;pScrandpThrindicatephosphorylatedserineandphosphorylatedthreonineaminoacidrcsidue,respectively.TheaminoacidnumbersarcbasedontlietopoisomeraseIlasequence-SwissProtaccessionPl1388andtopoisomeraselipsequence-SwissProtaccessionQ02880.\n物质代谢及酶的变化核酸代谢端粒酶Itisthoughtthatlengthorintegrityofchromosomeendisusedasamitoticcountingmechanisminvitro一EachmammalianchromosomeendhasadistinctiveDNA-proteinstructure,whichpreventsthedegradationandfusionofchromosomeendsbyhelpingdistinguishchromosomeendsfromadoublestrandbreakinthegenomicDNA.15\n物质代谢及酶的变化核酸代谢端粒酶Mammalianhaveastretchofasimplerepeatsequenceunit(TTAGGG)andin,lengthis15-20kb.Fiftyto200bpofthetelomericDNAshortensateachroundofmitosis.WhenaverageDNAreachesacriticallyshortlength,about4-7kb,isarrestedIrreversibly.15\n物质代谢及酶的变化核酸代谢，蛋白质代谢，糖代谢二/酶系统15\n物质代谢及酶的变化酶系统增殖相关和分化相关的酶转化相关和演进相关的酶转化相关细胞恶变的指标Q主要正常细胞发生转化，总可出现这类酶活性的改变。演进相关的酶酶活性于恶性程度呈平行关系的酶15\n肿瘤细胞的分化16肿瘤细胞的分化分化的概念同一来源的（特定的生理功能各种不同幼稚细胞A类型细胞（分化细胞）特定的生化特征特定的形态结构16\n细胞分化特点：稳定性全能性选择性•条祸卷[1]一'未分化恶性肿瘤是由于起源组织中的干细胞丧失了分化的能力。18\n肿瘤细胞分化异常的机制遗传学改变信号转化异常微环境的影响诱导分化治疗肿瘤18\n肿瘤细胞的生长细胞增殖活性的原位检测方法及意义细胞增殖活性：细胞增生快慢的能力含量测定确定增生细胞的比例Flowcytometry法DNAploidyandproliferativeactivityasrepresentedbytheS-phasefraction(SPF).AlinkexistsbetweenhighSPFvaluesandincreasedriskofrecurrenceanddeathforpatientswithprimaryBC,21\n肿瘤细胞的生长免疫组织化学方法OnlypaperspublishedinEnglishinpeerreviewedjournalsbeforeJune2004thatincludeatleast100evaluablepatientswereselected.Inaddition,theprognosticandpredictiveroleoftheproliferativemarkershadtobeassessedthroughmultivariateanalyses.Onehundredandthirty-twopapersfulfilledthesecriteriaand159516patientsanalyzed.>Ki-67-Severalmonoclonalantibodiesreactingwithdifferentproliferatingcellnuclearantigenshavebeendescribed,suchasPCNA,Ki-67andMIB1,KiS1andothers.TheKi-67/MIB1proteinhasa^rognosti^valueformanytypesofmalignanttumors.21\n肿瘤细胞的生长免疫组织化学方法细胞周期蛋白Thedifferentcyclins:theconcentrationriseandfallatspecificstagesthroughoutthecellcycle,haveatemporallydistinctandhighlyregulatedpatterri^fexpression,i.e.theyaresynthesizedanddegradedatspecificstagesofthecellcycle.CyclinEisthelimitingfactorforG1phaseprogressionandSphaseentryRecently,severalsplicevariantsofcyclinE1,whicharenotpresentinnormalcells,havealsobeendiscovered；whichstimulatecellstoprogressthroughthecellcyclemuchmoreefficientlythanthefulllengthcyclinE121\n肿瘤细胞的生长免疫组织化学方法细胞周期蛋白CyclinEwasprognosticinsevenoutof10studies.TheoverexpressionofcyclinEwasaccompaniedbytheappearanceoflowmolecularweight(LMW)isoforms,andbothwereareliableprognosticmarkerinstagekillBCpatients.HighlevelsofcyclinE1werepredictiveofresistancetotamoxifenadjuvanttherapyin\n108node-positiveBCpatients,independentlyofERstatus.i8