腫瘤病因發(fā)病機(jī)理20120221

腫瘤病因發(fā)病機(jī)理20120221

腫瘤的基本概念腫瘤

—機(jī)體在致瘤因子作用下，細(xì)胞遺傳物質(zhì)改變導(dǎo)致基因表達(dá)異常，細(xì)胞異常增殖而形成的新生物

腫瘤的基本概念Cancer

(medicalterm:malignant

neoplasm)isalarge,heterogeneousclassofdiseasesinwhichagroupofcellsdisplayuncontrolledgrowth,invasionthatintrudesuponanddestroysadjacenttissues,andoftenmetastasizes,whereinthetumorcellsspreadtootherlocationsinthebodyviathelymphaticsystemorthroughthebloodstream

腫瘤的基本概念Thesethreemalignantpropertiesofcancerdifferentiatemalignanttumorsfrombenigntumors,whichdonotgrowuncontrollably,directlyinvadelocally,ormetastasizetoregionallymphnodesordistantbodysiteslikebrain,bone,liver,orotherorgans頭痛癲癇發(fā)作眩暈咯血咳嗽呼吸困難淋巴結(jié)腫大肝腫大黃疸疼痛骨折中樞神經(jīng)壓迫腫瘤發(fā)生原因1、腫瘤發(fā)生的環(huán)境因素化學(xué)致癌—化學(xué)致癌物物理致癌—輻射致癌生物致癌—病毒致癌2、遺傳因素3、腫瘤發(fā)生的學(xué)說分類致癌物腫瘤化學(xué)致癌聯(lián)苯胺膀胱癌石棉肺癌、間皮瘤氯乙烯肝血管肉瘤砷肺癌、皮膚癌苯白血病鉻酸鹽肺癌氯甲醚肺癌焦?fàn)t逸散物肺癌化學(xué)致癌分類致癌物腫瘤物理致癌電離輻射甲狀腺癌、骨髓瘤、肺癌、乳腺癌紫外線皮膚癌生物致癌乳頭狀瘤病毒宮頸癌肝炎病毒肝癌EB病毒鼻咽癌人類T細(xì)胞白血病病毒人類T細(xì)胞白血病幽門螺桿菌胃癌黃曲霉毒素肝癌物理、生物致癌名稱原發(fā)腫瘤伴發(fā)腫瘤基因視網(wǎng)膜母細(xì)胞瘤視網(wǎng)膜母細(xì)胞瘤骨肉瘤RbWilms瘤腎母細(xì)胞瘤WAGR綜合征WT1遺傳性非腺瘤病性結(jié)直腸癌結(jié)直腸癌子宮內(nèi)膜癌輸尿管癌腎盂癌小腸癌hMLH家族性結(jié)腸息肉病結(jié)直腸腺瘤惡變APC遺傳性腫瘤與遺傳性腫瘤綜合征名稱原發(fā)腫瘤伴發(fā)腫瘤基因家族性乳腺癌1乳腺癌卵巢癌BRCA1家族性乳腺癌2乳腺癌胰腺癌BRCA2家族性黑色素瘤黑色素瘤胰腺癌P16Von-Hippel-lindau綜合征腎癌嗜鉻細(xì)胞瘤、血管瘤VHL遺傳性腫瘤與遺傳性腫瘤綜合征名稱原發(fā)腫瘤伴發(fā)腫瘤基因多發(fā)性內(nèi)分泌腺瘤I型胰島細(xì)胞瘤甲狀旁腺瘤、垂體瘤MEN1多發(fā)性內(nèi)分泌腺瘤II型甲狀腺癌甲狀旁腺瘤、嗜鉻細(xì)胞瘤MEN2神經(jīng)纖維瘤病I型神經(jīng)纖維瘤神經(jīng)鞘瘤、白血病NF2Li-Fraumeni綜合征肉瘤、乳腺癌白血病、腦腫瘤P53神經(jīng)纖維瘤病II型神經(jīng)纖維瘤、腦膜瘤膠質(zhì)細(xì)胞瘤、室管膜瘤NF2遺傳性腫瘤與遺傳性腫瘤綜合征腫瘤發(fā)生學(xué)說三階段學(xué)說兩次突變學(xué)說（克隆起源學(xué)說）

生殖細(xì)胞突變體細(xì)胞突變多階段學(xué)說干細(xì)胞起源學(xué)說腫瘤發(fā)生學(xué)說

變異細(xì)胞癌前病變

惡性腫瘤三階段學(xué)說啟動(dòng)階段促進(jìn)階段發(fā)展階段癌基因Ras

H-ras，K-ras,N-ras編碼產(chǎn)物：鳥苷酸結(jié)合蛋白，具有GTP酶活性，定位于細(xì)胞膜的內(nèi)側(cè)面，為細(xì)胞的第二信使K-ras突變：50%結(jié)腸癌、70%-90%胰腺癌、30%肺腺癌癌基因myc

編碼產(chǎn)物：P62蛋白，使細(xì)胞從G0期進(jìn)入G1期，細(xì)胞分裂效應(yīng)蛋白

myc

擴(kuò)增：30%-40%小細(xì)胞肺癌、神經(jīng)母細(xì)胞瘤、膠質(zhì)細(xì)胞瘤癌基因1、HER-2過表達(dá)：乳腺癌、卵巢癌、胃癌，PrognosticMarker2、C-met基因擴(kuò)增、重排、過量表達(dá)3、Bcl-2

基因：NHL中有易位活化的該基因的表達(dá)，與凋亡相關(guān)4、細(xì)胞周期蛋白：cyclin蛋白，淋巴瘤、乳腺癌、胃癌、食管癌有蛋白的過度表達(dá)5、端粒酶：染色體末端由端粒DNA和端粒蛋白質(zhì)構(gòu)成

H-RasstructurePDB121p,ribbonshowingstrandsinpurple,helicesinaqua,loopsingray.AlsoshownaretheboundGTPanalogandmagnesiumion.抑癌基因RbP53INK4基因家族CIP-KIP基因家族PTENFHITBRCAAPCDCCWT-1抑癌基因Rb：視網(wǎng)膜母細(xì)胞瘤基因基因缺失或突變骨肉瘤肺癌軟組織肉瘤抑癌基因p53：基因缺失或基因突變抑制細(xì)胞生長(zhǎng)，誘導(dǎo)細(xì)胞凋亡結(jié)腸癌、胃癌、乳腺癌、膀胱癌、肺癌、肝癌抑癌基因INK4基因家族：inhibitorsofcyclin-dendentkinases-4p15,p15,p18,p19

抑制細(xì)胞周期蛋白依賴性激酶（CDKs）的活性抑癌基因CIP-KIP基因家族：

p21,p27,p57

抑制細(xì)胞周期蛋白依賴性激酶（CDKs）的活性參與細(xì)胞分化、細(xì)胞周期及調(diào)控抑癌基因PTEN

Phosphataseandtensinhomolog(PTEN)isaproteinthat,inhumans,isencodedbythePTEN

gene.Mutationsofthisgeneareastepinthedevelopmentofmanycancers

StuctureofhumanPTEN抑癌基因PTENactsasatumorsuppressorgenethroughtheactionofitsphosphataseproteinproduct.Thisphosphataseisinvolvedintheregulationofthecellcycle,preventingcellsfromgrowinganddividingtoorapidly.ItisoneofthetargetsofanoncomiR,MIRN21.抑癌基因Thisgenewasidentifiedasatumorsuppressorthatismutatedinalargenumberofcancersathighfrequency.Theproteinencodedbythisgeneisaphosphatidylinositol-3,4,5-trisphosphate3-phosphatase抑癌基因Itnegativelyregulatesintracellularlevelsofphosphatidylinositol-3,4,5-trisphosphateincellsandfunctionsasatumorsuppressorbynegativelyregulatingAkt/PKBsignalingpathway抑癌基因PTENisoneofthemostcommonlylosttumorsuppressorsinhumancancerFrequentgeneticinactivationofPTENoccursinglioblastoma,endometrialcancer,andprostatecancerreducedexpressionisfoundinmanyothertumortypessuchaslungandbreastcancer抑癌基因BRCABothBRCAgenesaretumorsuppressorgenes

thatproduceproteinsthatareusedbythecellinanenzymaticpathwaythatmakesveryprecise,perfectlymatchedrepairstoDNAmoleculesthathavedouble-strandedbreaks.Thepathwayrequiresproteinsproducedbyseveralothergenes,includingCHEK2,FANCD2andATMHarmfulmutationsinanyofthesegenesdisablethegeneortheproteinthatitproduces抑癌基因ThecancerriskcausedbyBRCA1andBRCA2mutationsareinheritedinandominantfashionAmutatedBRCAgenecanbeinheritedfromeitherparent.Becausetheyareinheritedfromtheparents,theyareclassifiedashereditaryorgermlinemutationsratherthanacquiredorsomaticmutationsCancercausedbyamutatedgeneisahereditarycancerratherthanasporadiccancer

抑癌基因Mutationshavebeenassociatedwithincr