肿瘤的诱导分化和凋亡疗法

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1、第十六章　肿瘤的诱导分化和凋亡疗法受精卵的全能性人体细胞总数：1014类型：200多种细胞可以通过增殖来增加数目，那么细胞通过什么方法来改变其结构和功能呢？细胞分化（Differentiation)由同源细胞逐渐变为在形态结构、生理功能和生化特征等方面具有稳定差异的另一类型细胞的过程。干细胞干细胞(stemcells,SC)是一类具有自我复制能力(self-renewing)的多潜能细胞，在一定条件下，它可以分化成多种功能细胞。干细胞是一种未充分分化，尚不成熟的细胞，具有再生各种组织器官和人体的潜在功

2、能，医学界称为“万用细胞分化异常与肿瘤干细胞传统观念认为,肿瘤是由体细胞突变而成,每个肿瘤细胞都可以无限制地生长。但这无法解释肿瘤细胞似乎具有无限的生命力以及并非所有肿瘤细胞都能无限制生长的现象肿瘤干细胞：肿瘤中具有自我更新能力并能产生异质性肿瘤细胞的细胞。Selfrenewalanddifferentiationarerandom.Allcellshaveequalbutlowprobabilityofextensiveproliferation.Onlycellswithselfrenewalca

3、pacitycansustaintumorgrowth.Distinctclassesofcellsexistwithinatumor.Onlyasmalldefinablesubset,thecancerstemcellscaninitiatetumorgrowth.TwoGeneralModelsforCancerHeterogeneity异质性1.Allcancercellsarepotentialcancerstemcellsbuthavealowprobabilityofproliferat

4、ioninclonogenicassays（随机模式）2.Onlyasmalldefinablesubsetofcancercellsarecancerstemcellsthathavetheabilitytoproliferateindefinitely.（干细胞模式）OriginoftheTheoryofCancerStemCellsOnlyasmallsubsetofcancercellsiscapableofextensiveproliferationLiquidTumorsInvitroco

5、lonyformingassays:-1in10,000to1in100mousemyelomacellsobtainedfromascitesawayfromnormalhematopoieticcellswereabletoformcoloniesInvivotransplantationassays:-Only1-4%oftransplantedleukaemiccellscouldformspleencoloniesSolidTumors-Alargenumberofcellsarerequi

6、redtogrowtumorsinxenograftmodels-1in1,000to1in5,000lungcancer,neuroblastomacells,ovariancancercells,orbreastcancercellscanformcoloniesinsoftagarorinvivoTherapeuticimplicationsofCancerStemCellsMosttherapiesfailtoconsiderthedifferenceindrugsensitivitiesof

7、cancerstemcellscomparedtotheirnon-tumorigenicprogeny.Mosttherapiestargetrapidlyproliferatingnon-tumorigeniccellsandsparetherelativelyquiescentcancerstemcells.第一节诱导分化与肿瘤治疗肿瘤细胞在一定条件和诱导分化剂的作用下可以向正常细胞转化Wnt,Shh,andNotchpathwayshavebeenshowntocontributetothes

8、elf-renewalofstemcellsand/orprogenitorsinavarietyoforgans,includingthehaematopoieticandnervoussystems.Whendysregulated,thesepathwayscancontributetooncogenesis.Mutationsofthesepathwayshavebeenassociatedwithanumberofhumantumours,in