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1、第十六章 腫瘤的誘導(dǎo)分化和凋亡療法受精卵的全能性人體細(xì)胞總數(shù)：1014類(lèi)型：200多種細(xì)胞可以通過(guò)增殖來(lái)增加數(shù)目，那么細(xì)胞通過(guò)什么方法來(lái)改變其結(jié)構(gòu)和功能呢？細(xì)胞分化（Differentiation)由同源細(xì)胞逐漸變?yōu)樵谛螒B(tài)結(jié)構(gòu)、生理功能和生化特征等方面具有穩(wěn)定差異的另一類(lèi)型細(xì)胞的過(guò)程。干細(xì)胞干細(xì)胞(stemcells,SC)是一類(lèi)具有自我復(fù)制能力(self-renewing)的多潛能細(xì)胞，在一定條件下，它可以分化成多種功能細(xì)胞。干細(xì)胞是一種未充分分化，尚不成熟的細(xì)胞，具有再生各種組織器官和人體的潛在功
2、能，醫(yī)學(xué)界稱(chēng)為“萬(wàn)用細(xì)胞分化異常與腫瘤干細(xì)胞傳統(tǒng)觀念認(rèn)為,腫瘤是由體細(xì)胞突變而成,每個(gè)腫瘤細(xì)胞都可以無(wú)限制地生長(zhǎng)。但這無(wú)法解釋腫瘤細(xì)胞似乎具有無(wú)限的生命力以及并非所有腫瘤細(xì)胞都能無(wú)限制生長(zhǎng)的現(xiàn)象腫瘤干細(xì)胞：腫瘤中具有自我更新能力并能產(chǎn)生異質(zhì)性腫瘤細(xì)胞的細(xì)胞。Selfrenewalanddifferentiationarerandom.Allcellshaveequalbutlowprobabilityofextensiveproliferation.Onlycellswithselfrenewalca
3、pacitycansustaintumorgrowth.Distinctclassesofcellsexistwithinatumor.Onlyasmalldefinablesubset,thecancerstemcellscaninitiatetumorgrowth.TwoGeneralModelsforCancerHeterogeneity異質(zhì)性1.Allcancercellsarepotentialcancerstemcellsbuthavealowprobabilityofproliferat
4、ioninclonogenicassays（隨機(jī)模式）2.Onlyasmalldefinablesubsetofcancercellsarecancerstemcellsthathavetheabilitytoproliferateindefinitely.（干細(xì)胞模式）OriginoftheTheoryofCancerStemCellsOnlyasmallsubsetofcancercellsiscapableofextensiveproliferationLiquidTumorsInvitroco
5、lonyformingassays:-1in10,000to1in100mousemyelomacellsobtainedfromascitesawayfromnormalhematopoieticcellswereabletoformcoloniesInvivotransplantationassays:-Only1-4%oftransplantedleukaemiccellscouldformspleencoloniesSolidTumors-Alargenumberofcellsarerequi
6、redtogrowtumorsinxenograftmodels-1in1,000to1in5,000lungcancer,neuroblastomacells,ovariancancercells,orbreastcancercellscanformcoloniesinsoftagarorinvivoTherapeuticimplicationsofCancerStemCellsMosttherapiesfailtoconsiderthedifferenceindrugsensitivitiesof
7、cancerstemcellscomparedtotheirnon-tumorigenicprogeny.Mosttherapiestargetrapidlyproliferatingnon-tumorigeniccellsandsparetherelativelyquiescentcancerstemcells.第一節(jié)誘導(dǎo)分化與腫瘤治療腫瘤細(xì)胞在一定條件和誘導(dǎo)分化劑的作用下可以向正常細(xì)胞轉(zhuǎn)化Wnt,Shh,andNotchpathwayshavebeenshowntocontributetothes
8、elf-renewalofstemcellsand/orprogenitorsinavarietyoforgans,includingthehaematopoieticandnervoussystems.Whendysregulated,thesepathwayscancontributetooncogenesis.Mutationsofthesepathwayshavebeenassociatedwithanumberofhumantumours,in
