磁珠分选U251细胞系中的脑肿瘤干细胞及其耐药性的初步研究
|
摘要
1.目的
第一部分实验旨在运用磁珠分选技术(magnetic cell sorting,MACS)分选人多形性胶质母细胞瘤U251细胞系中的CD133+和CD133-亚群细胞;比较两个亚群细胞在增殖、分化及体内致瘤性等方面的差异,重点探讨CD133+细胞生物学特性;评价CD133作为脑肿瘤干细胞表面标志物的特异性与磁珠分选系统分选脑肿瘤干细胞的效率及特异性。第二部分实验的主要目的是研究和比较CD133+细胞亚群与CD133-细胞亚群耐药性的差异,并检测两个亚群细胞在ABC转运体、DNA修复及抗凋亡基因等表达的差异,初步分析CD133+细胞亚群的耐药机制。
2.方法
第一部分实验通过磁珠分选人多形性胶质母细胞瘤U251细胞系中的CD133+和CD133-细胞亚群,通过流式细胞仪检测分选的纯度和两个亚群细胞的细胞周期;利用MTT试验和单克隆形成率实验检测两个亚群细胞的增殖能力;运用免疫荧光检测CD133+细胞亚群的多向分化能力以及CD133+细胞增殖形成的BTS的分化情况;最后通过裸鼠移植实验,检测两个亚群细胞在裸鼠体内致瘤性的差异。第二部分实验在第一部分磁珠分选细胞的基础上,观察CD133+细胞与CD133-细胞在抗肿瘤药物作用下形态学的变化;利用MTT试验和流式细胞仪检测CD133+细胞亚群与CD133-细胞亚群对抗肿瘤药物替尼泊苷、卡莫司汀和顺铂的敏感性;通过RT-PCR方法检测两个亚群细胞在ABC转运子(MDR1、BCRP、MRP)、DNA修复基因(MGMT)及抗凋亡(Bcl-2)基因的表达差异。
3.结果
第一部分实验结果表明,在U251细胞系中只有大约4.5%的CD133+细胞,经过磁珠分选后,CD133+亚群细胞的细胞纯度可以提高到92.4%;分选后的CD133+细胞接种到含EGF和bFGF的无血清培养基中,具有强大的增殖能力,能增殖形成典型的BTS,而CD133-细胞不具有形成BTS的能力,生长曲线亦显示CD133+细胞增殖能力明显高于CD133-细胞;流式细胞仪实验显示CD133+细胞的细胞增殖率为40.1%,CD133-细胞的细胞增殖率为30.6%;单克隆形成率实验显示CD133+细胞能形成BTS的细胞比率达到78.5%-92.4%,而CD133-细胞仅有0.8-2.4%;分化实验免疫荧光实验显示CD133+细胞能分化为具有GFAP和NeuN成熟表型的肿瘤细胞,且CD133+细胞增殖形成的BTS亦能分化为具有GFAP和NeuN成熟表型的肿瘤细胞;裸鼠致瘤实验显示CD133+的致瘤率为71.42%,而CD133-细胞没有致瘤性。第二部分实验结果表明,CD133-细胞在抗肿瘤药物作用下凋亡形态学改变明显,CD133+细胞仍能维持生长;MTT实验显示,CD133-细胞对抗肿瘤药物替尼泊苷、卡莫司汀和顺铂的敏感性明显高于CD133+细胞;流式细胞仪试验显示在中等浓度的替尼泊苷作用下,CD133-细胞的凋亡明显,并出现明显的“亚G1峰”,而CD133+细胞并未受到明显抑制和杀灭;流式细胞仪检测显示CD133+细胞内的药物蓄积明显低于CD133-细胞;RT-PCR实验显示,MDR1、BCRP、MRP、MGMT和Bcl-2表达在CD133+明显高于CD133-细胞。
4.结论
U251细胞系中存在少量具有增殖、多向分化与体内致瘤能力的CD133+细胞,CD133+细胞是符合肿瘤干细胞定义的细胞亚群;磁珠分选是理想的脑肿瘤细胞分选系统;CD133+是U251细胞系中的耐药细胞亚群,高表达ABC转运体,DNA修复和抗凋亡基因可能是CD133+细胞耐药的重要机制。
OBJECTIVE The aim of the first part was to sort subpopulation of CD133+ and CD133- cells in the human Glioblastoma Multiforme(GBM)U251 cell line.To explore the difference of proliferation、differentiation and tumorigenic potential in vivo between the two subpopulation.The cytobiologic character of CD133+ subpopulation was the emphasis of this study;To investigate the specificity of CD133 to be specific surface marker(SSM)of brain tumor stem cells(BTSC)and the specificity and efficiency of the system of FACS sorting BTSC.The purpose of the second part was to compare the difference of drug sensitivity between the two subpolulation,and analysis the mechanism of chemoresistance by comparing the different expression of gene of ABC transporter、DNA repair and apoptosis.
METHODS In the first part,CD133+ and CD133- subpopulation cells in the human GBM U251 cell line were sorted by MACS.Single isolated CD133+ and CD133- cells was cultured in serum-free DMEM/F12 medium,containing B27(1∶50),basic fibroblast growth factor(bFGF,20μg/L),epidermal growth factor(EGF,20μg /L)or medium containing 10%fetal bovine serum.Cell cycle of the two subpopulation was analyzed by flow cytometry(FCM).MTT and monoclone forming rate(MFR)assay was performed to investigate the capacity of self-rewal and clonogenic potential of the subpopulation cells. Immunofluorescence staining was performed to investigate the multidiferentiation of CD133+ cells and brain tumor sphere(BTS), formed by CD133+ cells cultured in serum-free medium.At last,in order to investigate the tumorigenic potential of the two subpopulation in vivo, xenograft in BALB/c nude mice brain was performed.On the foundation of cell-sorting,the second part was aimed to analyze drug sensitivity of the two subpopulation,the cell morphology change was examined by phase microscopy after treated with anti-tumor drug.MTT and flow cytometry was performed to analyze the drug sensitivity of the two subpopulation to anti-tumor drug,Teniposide,Carmustine and Cisplatin. Finaly,ABC transporter,DNA repair and apoptosis gene expression of the two subpopulation was analyzed by RT-PCR.
RESULTS The first part show that,only4.5%cells was CD133+ in the total popul- ation of U251 cell line,and the purity of CD133+ cells in the CD133+ population can reach 92.4%after cell-sorting.The single CD133+ and CD133- cell was cultured in serum-free DMEM/F12 medium,containing B27(1∶50),basic fibroblast growth factor(bFGF, 20μg/L),epidermal growth factor(EGF,20μg /L)and serum-contain medium respectively.The CD 133+ cells exhibited powerful proliferation capacity.The single CD133+ cells could proliferate and form typical brain tumor sphere(BTS),while CD133- cells couldn't.And the cell growth curve showed that CD133+ cells proliferated remarkably faster than CD133- cells while cultured in serum-free medium.The cell proliferation index of CD133+ and CD133- cells was 40.1%and 30.6% respectively,showed by FCM.And the MFR of CD133+ and CD133-cells was 78.5-92.4%and 0.8-2.4%respectively.Immunofluorescence staining showed that,CD133+ cells and the BTS,forming by single CD133+ cells,could be induced to differentiate into mature neurocyte cells,which express NeuN and GFAP in the serum-containing medium. Xenograft assay showed that,CD133+ cells had tumorigenic potential in vivo,while CD133- hadn't.In the second part of this study,apoptotic morphologic change of CD133- cells was obvious in present of anti-tumor drug,while CD133+ cells could maintain survive.Anti-tumor drug assay showed that,CD133- cells were more sensitivite to Teniposide, Carmustine and Cisplatin than CD133+ cells.Treated with Teniposide, apoptotic percentage of CD133- cells were remarkerly higher than CD133+ cells,and "sub-Glpeak" appeared in CD133- subpopulation while CD133+ did not,showed by FCM.And FCM also showed that, accumulation of anti-tumor drug in CD133+ cells remarkably lower than CD133- cells.RT-PCR showed that,CD133+ cells expressed remarkably higher than CD133- cells in MDR1,BCRP,MRP1,MGMT and Bcl-2.
CONCLUSION The U251 cell line contained a small proportion of CD133+cells,which had the capacity of proliferation,multidifferentiation and tumorigenic potential in vivo.The subpopulation of CD133+ cells was the brain tumor stem cells subpopulation in U251. MACS was an optimizing cell sorting system in BTSC sorting.The subpopulation of CD133+ cells was the chemoresistant subpopulation in U251 cell line.High expression of ABC transporter,DNA repair and apoptosis maybe the important chemoresistance mechanism of CD133+ cells.
第一部分实验旨在运用磁珠分选技术(magnetic cell sorting,MACS)分选人多形性胶质母细胞瘤U251细胞系中的CD133+和CD133-亚群细胞;比较两个亚群细胞在增殖、分化及体内致瘤性等方面的差异,重点探讨CD133+细胞生物学特性;评价CD133作为脑肿瘤干细胞表面标志物的特异性与磁珠分选系统分选脑肿瘤干细胞的效率及特异性。第二部分实验的主要目的是研究和比较CD133+细胞亚群与CD133-细胞亚群耐药性的差异,并检测两个亚群细胞在ABC转运体、DNA修复及抗凋亡基因等表达的差异,初步分析CD133+细胞亚群的耐药机制。
2.方法
第一部分实验通过磁珠分选人多形性胶质母细胞瘤U251细胞系中的CD133+和CD133-细胞亚群,通过流式细胞仪检测分选的纯度和两个亚群细胞的细胞周期;利用MTT试验和单克隆形成率实验检测两个亚群细胞的增殖能力;运用免疫荧光检测CD133+细胞亚群的多向分化能力以及CD133+细胞增殖形成的BTS的分化情况;最后通过裸鼠移植实验,检测两个亚群细胞在裸鼠体内致瘤性的差异。第二部分实验在第一部分磁珠分选细胞的基础上,观察CD133+细胞与CD133-细胞在抗肿瘤药物作用下形态学的变化;利用MTT试验和流式细胞仪检测CD133+细胞亚群与CD133-细胞亚群对抗肿瘤药物替尼泊苷、卡莫司汀和顺铂的敏感性;通过RT-PCR方法检测两个亚群细胞在ABC转运子(MDR1、BCRP、MRP)、DNA修复基因(MGMT)及抗凋亡(Bcl-2)基因的表达差异。
3.结果
第一部分实验结果表明,在U251细胞系中只有大约4.5%的CD133+细胞,经过磁珠分选后,CD133+亚群细胞的细胞纯度可以提高到92.4%;分选后的CD133+细胞接种到含EGF和bFGF的无血清培养基中,具有强大的增殖能力,能增殖形成典型的BTS,而CD133-细胞不具有形成BTS的能力,生长曲线亦显示CD133+细胞增殖能力明显高于CD133-细胞;流式细胞仪实验显示CD133+细胞的细胞增殖率为40.1%,CD133-细胞的细胞增殖率为30.6%;单克隆形成率实验显示CD133+细胞能形成BTS的细胞比率达到78.5%-92.4%,而CD133-细胞仅有0.8-2.4%;分化实验免疫荧光实验显示CD133+细胞能分化为具有GFAP和NeuN成熟表型的肿瘤细胞,且CD133+细胞增殖形成的BTS亦能分化为具有GFAP和NeuN成熟表型的肿瘤细胞;裸鼠致瘤实验显示CD133+的致瘤率为71.42%,而CD133-细胞没有致瘤性。第二部分实验结果表明,CD133-细胞在抗肿瘤药物作用下凋亡形态学改变明显,CD133+细胞仍能维持生长;MTT实验显示,CD133-细胞对抗肿瘤药物替尼泊苷、卡莫司汀和顺铂的敏感性明显高于CD133+细胞;流式细胞仪试验显示在中等浓度的替尼泊苷作用下,CD133-细胞的凋亡明显,并出现明显的“亚G1峰”,而CD133+细胞并未受到明显抑制和杀灭;流式细胞仪检测显示CD133+细胞内的药物蓄积明显低于CD133-细胞;RT-PCR实验显示,MDR1、BCRP、MRP、MGMT和Bcl-2表达在CD133+明显高于CD133-细胞。
4.结论
U251细胞系中存在少量具有增殖、多向分化与体内致瘤能力的CD133+细胞,CD133+细胞是符合肿瘤干细胞定义的细胞亚群;磁珠分选是理想的脑肿瘤细胞分选系统;CD133+是U251细胞系中的耐药细胞亚群,高表达ABC转运体,DNA修复和抗凋亡基因可能是CD133+细胞耐药的重要机制。
OBJECTIVE The aim of the first part was to sort subpopulation of CD133+ and CD133- cells in the human Glioblastoma Multiforme(GBM)U251 cell line.To explore the difference of proliferation、differentiation and tumorigenic potential in vivo between the two subpopulation.The cytobiologic character of CD133+ subpopulation was the emphasis of this study;To investigate the specificity of CD133 to be specific surface marker(SSM)of brain tumor stem cells(BTSC)and the specificity and efficiency of the system of FACS sorting BTSC.The purpose of the second part was to compare the difference of drug sensitivity between the two subpolulation,and analysis the mechanism of chemoresistance by comparing the different expression of gene of ABC transporter、DNA repair and apoptosis.
METHODS In the first part,CD133+ and CD133- subpopulation cells in the human GBM U251 cell line were sorted by MACS.Single isolated CD133+ and CD133- cells was cultured in serum-free DMEM/F12 medium,containing B27(1∶50),basic fibroblast growth factor(bFGF,20μg/L),epidermal growth factor(EGF,20μg /L)or medium containing 10%fetal bovine serum.Cell cycle of the two subpopulation was analyzed by flow cytometry(FCM).MTT and monoclone forming rate(MFR)assay was performed to investigate the capacity of self-rewal and clonogenic potential of the subpopulation cells. Immunofluorescence staining was performed to investigate the multidiferentiation of CD133+ cells and brain tumor sphere(BTS), formed by CD133+ cells cultured in serum-free medium.At last,in order to investigate the tumorigenic potential of the two subpopulation in vivo, xenograft in BALB/c nude mice brain was performed.On the foundation of cell-sorting,the second part was aimed to analyze drug sensitivity of the two subpopulation,the cell morphology change was examined by phase microscopy after treated with anti-tumor drug.MTT and flow cytometry was performed to analyze the drug sensitivity of the two subpopulation to anti-tumor drug,Teniposide,Carmustine and Cisplatin. Finaly,ABC transporter,DNA repair and apoptosis gene expression of the two subpopulation was analyzed by RT-PCR.
RESULTS The first part show that,only4.5%cells was CD133+ in the total popul- ation of U251 cell line,and the purity of CD133+ cells in the CD133+ population can reach 92.4%after cell-sorting.The single CD133+ and CD133- cell was cultured in serum-free DMEM/F12 medium,containing B27(1∶50),basic fibroblast growth factor(bFGF, 20μg/L),epidermal growth factor(EGF,20μg /L)and serum-contain medium respectively.The CD 133+ cells exhibited powerful proliferation capacity.The single CD133+ cells could proliferate and form typical brain tumor sphere(BTS),while CD133- cells couldn't.And the cell growth curve showed that CD133+ cells proliferated remarkably faster than CD133- cells while cultured in serum-free medium.The cell proliferation index of CD133+ and CD133- cells was 40.1%and 30.6% respectively,showed by FCM.And the MFR of CD133+ and CD133-cells was 78.5-92.4%and 0.8-2.4%respectively.Immunofluorescence staining showed that,CD133+ cells and the BTS,forming by single CD133+ cells,could be induced to differentiate into mature neurocyte cells,which express NeuN and GFAP in the serum-containing medium. Xenograft assay showed that,CD133+ cells had tumorigenic potential in vivo,while CD133- hadn't.In the second part of this study,apoptotic morphologic change of CD133- cells was obvious in present of anti-tumor drug,while CD133+ cells could maintain survive.Anti-tumor drug assay showed that,CD133- cells were more sensitivite to Teniposide, Carmustine and Cisplatin than CD133+ cells.Treated with Teniposide, apoptotic percentage of CD133- cells were remarkerly higher than CD133+ cells,and "sub-Glpeak" appeared in CD133- subpopulation while CD133+ did not,showed by FCM.And FCM also showed that, accumulation of anti-tumor drug in CD133+ cells remarkably lower than CD133- cells.RT-PCR showed that,CD133+ cells expressed remarkably higher than CD133- cells in MDR1,BCRP,MRP1,MGMT and Bcl-2.
CONCLUSION The U251 cell line contained a small proportion of CD133+cells,which had the capacity of proliferation,multidifferentiation and tumorigenic potential in vivo.The subpopulation of CD133+ cells was the brain tumor stem cells subpopulation in U251. MACS was an optimizing cell sorting system in BTSC sorting.The subpopulation of CD133+ cells was the chemoresistant subpopulation in U251 cell line.High expression of ABC transporter,DNA repair and apoptosis maybe the important chemoresistance mechanism of CD133+ cells.
引文
[1]曾益新编著,肿瘤学.北京:人民卫生出版社.2003,366-393.
[2]Bonnet D,Dick JE.Human acute myeloid leukemia is organized as a hierarchy thatoriginates from a primitive hematopoietic cell.Nat Med,1997,3(7):730-737
[3]Al-Hajj M,Wicha MS,Benito-Hemandez A,et al.Prospective identification of tumorigenic breast cancer cells.Proc Natl Acad Sci U S A,2003,100(7):3983-3988
[4]Singh SK,Clarke ID,Terasaki M,et al.Identification of a cancer stem cell in human brain tumors.Cancer Res,2003,63(18):5821-5828
[5]Hemmati HD,Nakano I,Lazareff JA,et al.Cancerous stem cells can arise from pediatric brain tumors.Proc Natl Acad Sci U S A,2003,100(25):15178-15183
[6]Kondo T,Setoguchi T,Taga T.et al.Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line.Proc Natl Acad Sci U S A,2004,101(3):781-786
[7]Yuan X,Curtin J,Xiong Y,et al.Isolation of cancer stem cells from adult glioblastoma multiforme.Oncogene,2004,23(58):9392-9400
[8]方加胜,邓永文,李茗初,等.神经上皮来源脑肿瘤中肿瘤干细胞的分离培养与鉴定.中华医学杂志,2007,87:298-303.
[9]李茗初,邓永文,伍军,等.髓母细胞瘤中脑肿瘤干细胞的分离培养及鉴定.癌症.2006,25(2):241-246.
[10]Kim C F,Jackson E L,Woolfenden A E,et al.Identification of bronchioalveolar stem cells in normal lung and lung cancer.Cell.2005,121(6):823 - 835.
[11]CollinsAT,Berry PA,Hyde C,et al.Prospective identification of tumorigenic p rostate cancer stem cells.Cancer Res,2005,65:10946- 10951.
[12]Heidt DG,Li C,Mollenberg N,et al.Identification of pancreatic cancer stem cells.J Surg Res,2006,130:194 -195.
[13]Reya T,Morrison SJ,Clarke MF,et al.Stem cells,cancer,and cancer stem cells.Nature,2001,414(6859):105-111
[14]Soltysova A,Altanerova V,Altaner C.Cancer stem cells.Neoplasma,2005,52 (6):435-440.
[15]Dean M,Fojo T,Bates S.Tumour stem cells and drug resistance.Nat Rev Cancer 2005,5:275-284.
[16]Chen L,Shervington A.Chemoresistance in gliomas.Mol Cell Biochem.2008,
[17]Eramo A,Vitiani LR,Zeuner A,et al.Chemotherapy resistance of glioblastoma stem cells.Cell Death and Differentiation.2006,13:1238-1241.
[18]Raaijmakers M,de Grouw E,Heuver L,et al.Breast cancer resistance protein in drug resistance of primitive CD34+CD38-cells in acute myeloid leukemia.Clinical cancer research.2005.11:2436-2444.
[19]宋永平,房佰俊,魏旭东,等.K562/Vp16细胞系中边缘细胞对伊马替尼耐药机制的初步研究.2005,26(11):669-673.
[20]Clevers H.Stem cells,asymmetric division and cancer.Nature.2005,37:1027-1028.
[21]Galli R,Gritti A,Bonfanti L,et al.Neural stem cells:an overview.Circ Res,2003,92(6):598-608
[22]Berger F,Gay E,Pelletier L,et al.Development of gliomas:potential role of asymmetrical cell division of neural stem cells.Lancet Oncol,2004,5(8):511-514.
[23]Nish H,Nishimura S,Higashiura M,et al.A new method for histamine release from purified peripheral blood basophils using monoclonal antibody-coated magnetic beads.J Immunol Methods,2000,240(1-2):39-46.
[24]Siegel D L.Selecting antibodies to cell surface antigens usingrnagnetic sorting techniques.MethodsMol Biol,2002,178:219 - 226.
[25]Miraglia S,Godfrey W,Yin AH,et al.A novel five-transmembrane hematopoietic stem cell antigen:isolation,characterization,and molecular cloning.Blood,1997,90(12):5013-5021
[26]Uchida N,Buck DW,He DP,et al.Direct isolation of human central nervous system stem cells.Proc Natl Acad Sci,2000,97(26):14720-14725
[27]Vescovi LA,Galli R,Reynolds BA.Brain tumor stem cells.Nature Reviews,2006,6:425-436.
[28]司徒镇强,吴军正主编.细胞培养.北京:世界图书出版公司,1996:244-245.
[29]Lal S,Lacrolx M,Tofilon P,et al.An implantable guide-screw system for brain tumor studies in small animals.J Neurosurg,2000,92:326-333.
[30]Lassman AB.Molecular biology of gliomas.Curr Neurol Neurosci Rep,2004,4(3):228-233.
[31]刘艳辉,毛伯镛,姜曙等.髓母细胞瘤中表皮生长因子受体的表达及基因扩增分析.中华神经外科疾病研究杂志,2002,1(1):51-53
[32]Ueba T,Takahashi JA,Fukumoto M,et al.Expression of fibroblast growth factor receptor-1 in human glioma and meningioma tissues.Neurosurgery,1994,34(2):221-225.
[33]Duplan SM,Theoret Y,Kenigsberg RL.Antitumor activity of fibroblast growth factors(FGFs)for medulloblastoma may correlate with FGF receptor expression and tumor variant.Clin Cancer Res,2002,8(1):246-257.
[34]Aold T,Kato S,Fox JC et al.Inhibition of autocrine fibroblast growth factor signaling by the adenovirus-mediated expression of an antisense transgene or a dominant negative receptor in human glioma cells in vitro.Int.J.Oncol.2002,21(3):629-636.
[35]Holland,EC,Hivelv WP,Depinho RA,et al.A constitutively active epidermal growth factor receptor cooperates with disruption of G1 cell-cycle arrest pathways to induce glioma-like lesions in mice.Genes Dev.1998,12(23):3675-3685.
[36]Holland,EC.Progenitor cells and glioma formation.Curr.Opin.Neurol.2001,14(6):683-688.
[37]Tropepe V,Sibilia M,Cinma BG,et al.Distinct Neural Stem Cells Proliferate in Response to EGF and FGF in the Developing Mouse Telencephalon.Dev Biol,1999,208(1):166-188
[38]Sigh SK,Hawkins C,Clarke ID,et al.Identification of human brain tumor initiating cells.Nature.2004,432:396-401.
[39]凌诒萍主编.细胞生物学.北京:人民卫生出版社,2001.121-128
[40]Miraglia S,Godfrey W,Yin AH,et al.A novel five-transmembrane hematopoietic stem cell antigen:isolation,characterization,and molecular cloning.Blood,1997,90(12):5013-5021
[41]Vescovi AL,Snyder EY.Establishment and properties of neural stem cell clones:plasticity in vitro and in vivo.Brain Pathol,1999,9(3):569-598.
[42]Tanja Z,Paul RS,Juan RS,et al.Neural Stem Cells-Methods and Protocols.Totowa,New Jersey,USA..Humana Press Inc,2002.149-297
[43]Jeong SW,Chu K,Jung KH,et al.Human neural stem cell transplantation promotes functional recovery in rats with experimental intracerebral hemorrhage.Stroke,2003,34(9):2258-2263
[44]Kilpatrick TJ,Bartlett PF.Cloning and growth of multipotential neural precursors:requirements for proliferation and differentiation.Neuron,1993,10(2):255-265
[45]Gritti A,Rosati B,Lecchi M,et al.Excitable properties in astrocytes derived from human embryonic CNS stem cells.Eur J Neurosci,2000,12(10):3549-3559
[46]Gage FH.Mammalian neural stem cells.Science,2000,287(5457):1433-1438
[47]Galli R,Binda E,Orfanelli U,et al.Isolation and characterization of tumorigenic,stem-like neural precursors from human glioblastoma.Cancer Res,2004,64(19):7011-7021
[48]Ignatova TN,Kukekov VG.,Laywell ED,et al.Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro.Glia,2002,39(3):193-206
[49]余爽,张京钟,张海燕等.免疫磁珠体外纯化人胎脑中CD133阳性干细胞的实验研究.神经解剖学杂志,2004,20(3):271-274
[50]Goodell MA,Brose K,Paradis G,et al.Isolation and functional properties of murine hematopoietic stem cell that are replicating in vivo.J Exp Med,1996,183(4):1797-1806.
[51]王红晖,聂捷林,李莹辉,等.成体干细胞中的SP细胞群.中国生物工程杂志,2005,25(12):75-78.
[52]Lubna P,Tammy C,Robin S,et al.Side population is enriched in tumorigenic,stem-like cancer cells,whereas ABCG2+ and ABCG2- cancer cells are similar tumorigenic.Cancer Res,2005,65(14):6207-6219.
[53]Hirschmann-Jax C,Foster AE,Wulf GG,et al.A distinct "side population" of cells with high drag effiux capacity in human tumor cells.PNAS,2004,101:14228- 14233.
[54]Naotsugu H,Tohru U,Hiroshi I,et al.Characerization of a side population of cancer cells from human gasterointestinal system.Stem Cells,2006,24:506-513.
[55]张卓然.实用细胞培养技术[M].北京:人民卫生出版社.1999.97.
[56]J Kurz Eu,Leader KB,Krol DJ,et al.Modulation of human DNA topoisomerase Iialpha funtion by interaction with 14-3-3epsilon.J Biol Chem,2000,275(18):13948 -13954.
[57]Zaman GJ,Versantvoort CH,Smit JJ,et al.Analysis of the expression of MRP,the gene for a new putative transmembrane drug transporter,in human multidrug resistant lung cancer cell lines[J].Cancer Res,1993,53(8):1747-1750.
[58]吕辉.BCRP表达调节及运用RNA干扰技术逆转其介导的肿瘤多药耐药研究.[硕士学位论文].长沙:中南大学,2005.
[59]Yamaue H,Tanimura H,Tsunoda T,et al.Cheosensitivity testing with highly pughly purified fresh human tumor cells with the MTT olorimetric assay.Eur J Canoe,1991,27(10):1258-1263.
[60]Liu G,Yuan XP,Zeng ZH:Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma.Molecular Cancer,2006,5:67.
[61]Yin D,Xie D,Hofmann WK,et al.DNA repair gene 06 -methylguanine - DNA methyltransferase:promoter hypermethylation associated with decreased expression and G:C to A:T mutations of p53 in brain tumors.Mol Carcinog.2003,36(1):23.
[62]Nagane M,Asai A,Shibui S,et al.Expression pattern of chemoresistance related for proper selection of anticancer drugs.Jpa J Clin Oncol,1999,29(1):527.
[63]胡苹,左焕琮,马雄君,等.06甲基鸟嘌呤DNA转移酶在神经胶质瘤中的表达及其与亚硝脲耐药的关系.中日友好医院学报,2003,17(4):216.
[64]Scharenberg,C.W.,Harkey,M.A.& Torok-Storb,B.TheABCG2 transporter is an efficient Hoechst 33342 effiux pump and is preferentially expressed by immature humanhematopoietic progenitors.Blood 2002,99:507-512.
[65]Gottesman,M.M.,Fojo,T.& Bates,S.E.Multidrug resistance in cancer:role of ATP-dependent transporters .Nature Rev. Cancer.2002, 2,48-58.
[66] Dean M., Rzhetsky A.,Allikmets R. The human ATPbinding cassette (ABC) transporter superfamily. Genome Res.2001,11,1156-1166.
[67] Zhou, S., Zong, Y., Lu, T., et al. Hematopoietic cells from mice that are deficient in both Bcrp1/Abcg2 and Mdr1a/1b develop normally but are sensitized tomitoxantrone. Biotechniques 2003,35:1248-1252.
[68] Lin JH , Yamazaki M. Clinical relevance of P-glycoprotein in drugtherapy . Drug Metab Rev, 2003 , 35 (4) :417- 454.
[69] Haimeur A , Conseil G, Deeley RG, et al . The MRP2related and BCRP/ABCG2 multidrug resistance proteins : biology , substrate specificity and . regulation. Curr Drug Metab, 2004, 5(1) :21-53.
[70] Doyle LA , Yang W, Abruzzo LV , et al . A multidrug resistance transporter from human MCF-7 breast cancer cells .Proc Natl Acad Sci USA ,1998 , 95 (26): 15665 -15670.
[71] Altenberg GA. Structure of multidrug-resistance proteins of the ATP-binding cassette(ABC) superfamily. Curr med chem-Anti cancer angents. 2004,4:53-62.
[72] Kage K, Tsukahara S , Sugiyama T , et al . Dominant negative inhibition of breast cancer resistance protein as drug efflux pump through the inhibition of S2S dependent homodimerization. Int J Cancer, 2002 , 97 (5) :626 - 630.
[73] Islam MO, Kanemura Y, Tajria J, et al. Characterization of ABC transporter ABCB1 expressed in human neural stem /progenitor cells. FEBS Lett, 2005, 579: 3473-3480.
[74] Krishnamurthy P , Schuetz JD. Role of ABCG2/ BCRP in Biology. Annu Rev Pharmacol Toxicol. 2006 ,46 :381 - 410.
[75] Zhou S , Morris JJ , Barnes Y, et al. Bcrp1 gene expression is required for nomal numbers of side population stem cell in mice ,and confers relative protection to mitoxantrone in hematopoietic cells in vivo . PNAS ,2002 ,99(19) : 12339 -12344.
[76] Zhou S , Schuetz JD , Bunting KD , et al. The ABC transporter Bcrp1/ ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med, 2001 ,7(9): 1028 -1034.
[77]de Fiqueiredo-Pontes LL,Pintao MC,Oliveira LC,et al.Determination of P-glycoprotein,MDR-related protein 1,breast cancer resistance protein,and lung-resistance protein expression in leukemic stem cells of acute myeloid leukemia.Cytometry B Clin Cytom.2008,[ahead of print].
[78]Kitada S,Pedersen IM,Schimmer AD,et al.Dysregulation of apoptosis genes in hematopoietic malignancies.Oncogene 2002,21:3459-3474.
[79]Schimmer AD:Inhibitor of apoptosis proteins:translating basic knowledge into clinical practice.Cancer Res 2004,64:7183-7190.
[80]Safatle - Ribeiro AV,Ribeiro U J r,Corbett CE,et al.Prognostic value of immunohistochemistry in gastric neuroendocrine(carcinoid)tumors.Eur J Gastroenterol Hepatol,2007,19(1):21.
[81]任勇,仲召阳,陈寿松,等.大肠腺瘤及腺癌细胞凋亡与p53和bcl-2的表达.华南国防医学杂志,2005,19(5):11.
[82]赵松,段惠军,齐凤英,等.Bcl-2、p53在皮肤肿瘤中的表达及意义.肿瘤研究与临床,2005,17(3):161.
[83]Zavrides H,Zizi - sermpetzoglou A,Elemenoglou I,et,al.Immunohistochem-ical express of bcl - 2 in UICC stage Ⅰ and Ⅲ colorectal carcinoma patients:correla- tion with c - erbB - 2,p53,ki - 67,CD44,laminin and collagen Ⅳ in evaluating prognostic singnificance.Pol J Pathl,2006,57(3):149.
[84]宋兰云,王学文,胡晓丽,等.凋亡相关bcl-2基因族在儿童神经母细胞瘤中的表达.Tanjin Med J.2005,33(1):20.
[85]Andreeff M,Jiang S,Zhang X,et al.Expression of Bcl-2-related genes in normal and AML progenitors:changes induced by chemotherapy and retinoic acid.Leukemia 1999,13:1881-1892.
[86]Lu Z,Wu Z,Mo Y.Regulation of Bcl-2 expression by Ubc9.Exp cell Res.2006,312:1865-1875.
[87]Weller M,Malipiero U,Aguzzi A,et al.Protooncogene bcl-2 Gne transfer abrogates Fas/APO-1 antibody-mediated apoptosis of human malignant glioma cells and confers resistance to chemotherapeutic drugs and therapeutic irradiation.J Clin Invest.1995,95:2633-2643
[88]Wei L,Cui L,Snider J,Rivkin M.et al.Transplantation of embryonic stem cells overexpressing Bcl-2 promotes functional recovery after transient cerebral ischemia.Neurobiol Dis.2005,19:183-193
[89]房佰俊,宋永平,魏旭东,等.慢性粒细胞性白血病干细胞抗伊马替尼机制的初步研究.第一届国际肿瘤干细胞学术会议论文集.杭州,2007,85.
[1]黄文清编著.神经肿瘤病理学.北京:军事医学科学出版社,2001.41-54.
[2]Reya T,Morrison SJ,Clarke MF,et al.Stem cells,cancer,and cancer stem cells.Nature,2001,414(6859):105-111.
[3]Recht L,Jang T,Savarese T,et al.Neural stem cells and neuro-oncology:Quo vadis? J Cell Biochem,2003;88(1):11-19.
[4]Lapidot T,Sirard C,Vormoor J,et al.A cell initiating human acute myeloid leukaemia after transplantation into SCID mice.Nature,1994,367(6464):645-648
[5]Bonnet D,Dick JE.Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell.Nat Med,1997,3(7):730-737
[6]Al-Hajj M,Wicha MS,Benito-Hernandez A,et al.Prospective identification of tumorigenic breast cancer cells.Proc Natl Acad Sci U S A,2003,100(7):3983-3988
[7]Ignatova TN,Kukekov VG.,Laywell ED,et al.Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro.Glib,2002,39(3):193-206
[8]Singh SK,Clarke ID,Terasaki M,et al.Identification of a cancer stem cell in human brain tumors.Cancer Res,2003,63(18):5821-5828
[9]Hemmati HD,Nakano I,Lazareff JA,et al.Cancerous stem cells can arise from pediatric brain tumors.Proc Natl Acad Sci U S A,2003,100(25):15178-15183
[10]Kondo T,Setoguchi T,Taga T.et al.Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line.Proc Natl Acad Sci U S A,2004,101(3):781-786
[11]Singh SK,Hawkins C,Clarke ID,et al.Identification of human brain tumour initiating cells.Nature,2004,432(7015):396-401
[12]Yuan X,Curtin J,Xiong Y,et al.Isolation of cancer stem cells from adult glioblastoma multiforme.Oncogene,2004,23(58):9392-9400
[13]Galli R,Binda E,Orfanelli U,et al.Isolation and characterization of tumorigenic,stem-like neural precursors from human glioblastoma.Cancer Res,2004,64(19):7011-7021
[14]李茗初,陈风华,邓永文等.悬浮法培养C6胶质瘤细胞系和该细胞系中脑肿瘤干细胞的分离.中国现代医学杂志,2004,14(24):57-60
[15]方加胜,邓永文,李茗初,等.神经上皮来源脑肿瘤中肿瘤干细胞的分离培养与鉴定.中华医学杂志,2007,87:298-303.
[16]李茗初,邓永文,伍军,等.髓母细胞瘤中脑肿瘤干细胞的分离培养及鉴定.癌症.2006,25(2):241-246.
[17]Vescovi LA,Galli R,Reynolds BA.Brain tumor stem cells.Nature Reviews,2006,6:425-436.
[18]Hamburger AW,Salmon SE.Primary bioassay of human tumor stem cells.Science,1977,197(4302):461-463
[19]Rosenblum ML,Gerosa MA,Wilson CB,et al.Stem cell studies of human malignant brain tumors.Part 1:Development of the stem cell assay and its potential.J Neurosurg,1983,58(2):170-176.
[20]巢卫,彭祥鄂.人体肿瘤干细胞软琼脂集落培养-Ⅱ双层琼脂法.癌症,1987,6(01):30-33+89
[21]Suslov ON,Kukekov VG,Ignatova TN and Steindler DA.Neural stemcell heterogeneity demonstrated by molecular phenotyping of clonalneurospheres.Proc.Natl.Acad.Sci.USA.2002 99:14506-14511
[22]]Nish H,Nishimura S,Higashiura M,et al.A new method for histamine release from purified peripheral blood basophils using monoclonal antibody-coated magnetic beads.J Immunol Methods,2000,240(1-2):39-46.
[23]Goodell MA,Brose K,Paradis G,et al.Isolation and functional properties of murine hematopoietic stem cell that are replicating in vivo.J Exp Med,1996,183(4):1797-1806.
[24]Galli R,Gritti A,Bonfanti L,et al.Neural stem cells:an overview.Circ Res,2003,92(6):598-608
[25] Lin H, Schagat T. Neuroblasts: a model for the asymmetric division of stem cells. Trends Genet,1997,13(1):33-39
[26] Kilpatrick TJ, Bartlett PF. Cloning and growth of multipotential neural precursors: requirements for proliferation and differentiation. Neuron, 1993, 10(2): 255-265
[27] Gritti A, Rosati B, Lecchi M, et al. Excitable properties in astrocytes derived from human embryonic CNS stem cells. Eur J Neurosci, 2000, 12(10):3549-3559
[28] Gage FH. Mammalian neural stem cells. Science, 2000,287(5457):1433-1438
[29] Miraglia S, Godfrey W, Yin AH, et al. A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and .molecular cloning. Blood, 1997, 90(12):5013-5021
[30] Galderisi U, Cipollaro M, Giordano A. Stem cells and brain cancer. Cell Death and Differentiation,2006,13:5-11.
[31] Almqvist PM, Mah R, Lendahl U,et al. Immunohistochemical detection of nestin in pediatric brain tumors. Histochem. Cytochem.2002, 50: 147-158
[32] Wang J, Guo LP, Chen LZ, et al. Identification of cancer stem cell-like side population in human nasopharyngeal carcinoma cell line. Cancer Res. 2007,67(8): 3716-3724.
[33] 曾益新主编．肿瘤学．北京：人民卫生出版社,2003．11—236
[34] Holland, EC. Gliomagenesis: genetic alterations and mouse models. Nat Rev Genet, 2001,2(2): 120-129
[35] Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer.Nat Rev Cancer, 2003, 3(12):895-902
[36] Mondal D, Pradhan L, LaRussa VF. Signal transduction pathways involved in the lineage-differentiation of NSCs: can the knowledge gained from blood be used in the brain? Cancer Invest, 2004,22(6): 925-943
[37] Varnum-Finney B, Xu L, Brashem-Stein C, et al. Pluripotent,cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat. Med,2000, 6: 1278-1281
[38] Lee HY, Kleber M, Hari L, et al.Instructive role of Wnt/beta-catenin in sensory fate specification in neural crest stem cells. Science ,2004,303: 1020-1023
[39] Bhardwaj G, Murdoch B, Wu D, et al.Sonic hedgehog induces the proliferationof primitive human hematopoietic cells via BMP regulation. Nat. Immunol,2001, 2:172-180
[40] Ruiz i Altaba A, Sanchez P and Dahmane N.Gli and hedgehog in cancer: tumours, embryos and stem cells. Nat. Rev. Cancer,2002,2: 361-372
[41] Brivanlou AH and Darnell Jr JE. Signal transduction and the control of gene expression. Science ,2002,295: 813-818
[42] Wechsler-Reya RJ and Scott MP .Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Neuron ,1999,22: 103-114
[43] Machold R, Hayashi S, Rutlin M, et al. Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches. Neuron,2003, 39: 937-950
[44] Rao G, Pedone CA, Valle LD, et al. Sonic hedgehog and insulin-like growth factor signaling synergize to induce medulloblastoma formation from nestin-expressing neural progenitors inmice. Oncogene,2004, 23: 6156-6162
[45] Pietsch T, Taylor MD and Rutka JT .Molecular pathogenesis of childhood brain tumors. J. Neurooncol. 2004,70: 203-215
[46] Das AV, James J, Zhao X, et al.Identification of c-Kit receptor as a regulator of adult neural stem cells in the mammalian eye: interactions with Notch signaling. Dev. Biol,2004,273: 87-105
[47] Hitoshi S, Seaberg RM, Koscik C, et al. Primitive neural stem cells from the mammalian epiblast differentiate to definitive neural stem cells under the control of Notch signaling. Genes Dev.2004,18: 1806-1811
[48] Joutel A,Tournier-Lasserve E. Notch signalling pathway and human diseases. Semin.Cell.Dev.Biol, 1998,9(6):619-25。
[49] Fan X, Mikolaenko I, Elhassan I, et al. Notchl and notch2 have opposite effects on embryonal brain tumor growth. Cancer Res,2004,64: 7787-7793
[50] Lee HY, Kleber M, Hari L, et al. Instructive role of Wnt/beta-catenin in sensory fate specification in neural crest stem cells. Science,2004, 303: 1020-1023
[51] Valk-Lingbeek ME, Bruggeman SW and van Lohuizen M . Stem cells and cancer; the polycomb connection. Cell,2004,118: 409-418
[52] Molofsky AV, Pardal R, Iwashita T, et al. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 2003,425: 962-967
[53] Valk-Lingbeek ME, Braggeman SW et al. Stem cells and cancer; the polycomb connection. Cell,2004,118: 409-418
[54] Gentao L, Xiangpeng Y, Zhaohui Z, et al. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in globlastoma. Molecular Cancer,2006,5:67.
[55] Linheng Li ,William B. Neaves. Normal stem cells and cancer stem cells: the niche matters. Cancer Res,2006,66(9):4553-4557.
[56] Uchida K, Mukai M, Okano H, et al. Possible oncogenicity of subventricular zone neural stem cells: case report. Neurosurgery, 2004, 55(4):977-987
[57] Rao G, Pedone CA, Coffin CM, et al. c-Myc enhances sonic hedgehoginduced medulloblastoma formation from nestin-expressing neural progenitors in mice. Neoplasia, 2003, 5(3): 198-204
[58] Almqvist PM, Mah R, Lendahl U, et al.Immunohistochemical detection of nestin in pediatric brain tumors.Histochem. Cytochem.2002, 50: 147-158
[59] Alvarez-Buylla A and Garcia-Verdugo JM .Neurogenesis in adult subventricular zone. Neurosci. 2002,22: 629-634
[60] Sutton LN, Phillips P and Lange B . Midline supratentorial tumors.Neurosurg. Clin. North Am, 1992, 3: 821-837
[61] Pomeroy SL, Tamayo P, Gaasenbeek M, et al. Prediction of central nervous system embryonal tumor outcome based on gene expression[J]. Nature, 2002, 415(6870): 436-442.
[62] Leung C, Lingbeek M, Shakhova O, et al. Bmil is essential for cerebellar development and is overexpressed in human medulloblastoma. Nature, 2004, 428(6980):337-341.
[63] Groszer M, Erickson R, Scripture-Adams DD, et al. Negative regulation of stem cell/progenitor cell proliferation by the PTEN tumor suppressor gene in vivo. Science, 2001, 294(5549):2186- 2189.
[64] Bachoo RM, Maher EA, Ligon KL, et al. Epidermal growth factor receptor and Ink4a/Arf. Convergent mechanisms governing terminal differentiation and transfer- mation along the neural stem cell to astrocyte axis. Cancer Cell. 2002, 1:269-277.
[65] Matsui WH, Huff CA, Wang Q. Characterization of clonogenic multiple myeloma cells. Blood,2004,103:2332-2336.
[66] Yilmaz OH, Valdez R, Theisen BK, et al. Pten dependence distinguishes hematopoietic stem cells from leukaemia-initiating cells. Nature, 2006,441 (25): 475-482.
[67] Chen MF, Lin CT, Chen WC, et al. The sensitivity of human mesenchymal stem cell to ionizing radiation..Int Radiation Oncology Biol Phys, 2006, 66(1):244-253.
[68] Bao S, Wu Q, Mclendon RE, et al. Glioma stem cell promote radioresistance by preferential activation of the DNA damage response. Nature, 2006, 444(7120):756- 760.
[69] Ohno R, Asou N, Ohnishi K.Treatment of acute promyelocytic leukemia: strategy toward further increase of cure rate. Leukemia,2003,17:1454-1463.
[70] Aguado T, Carracedo A, Julien B, et al. Cannabinoids induceglioma stem-like cell differentiation and inhibitgliomagenesis. J Biol Chem, 2007, 2: [ahead of print].
[1]曾益新编著.肿瘤学.北京:人民卫生出版社.2003,366-393.
[2]Reya T,Morrison SJ,Clarke MF,et al.Stem cells,cancer,and cancer stem cells.Nature,2001,414(6859):105-111
[3]Soltysova A,Altanerova V,Altaner C.Cancer stem cells.Neoplasma,2005,52(6):435-440.
[4]Dean M,Fojo T,Bates S.Tumour stem cells and drug resistance.Nat Rev Cancer 2005,5:275-284.
[5]Bruce W R,Van Der Gaag H.A quantitative assay for t he number of murine lymphoma cells capable of proliferation in vivo.Nature,1963,199:79 - 80.
[6]Wodinsky I,Swiniarski J,Kensler C J.Spleen colony studies of leukemia L1210.Ⅳ.Sensitivities of L1210 and L1210/ 6-MP to triazenoimi dazolecarboxamid- es- a preliminary report.Cancer Chemother Rep.1968,52(3):393 - 398.
[7]Hamburger A W,Salmon S E.Primary bioassay of humanturnor stem cells.Science.1977,197(4302):461 - 463.
[8]Bonnet D,Dick JE.Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell.Nat Med,1997,3(7):730-737
[9]Al-Hajj M,Wieha MS,Benito-Hernandez A,et al.Prospective identification of tumorigenic breast cancer cells.Proc Natl Acad Sci U S A,2003,100(7):3983-3988
[10]Singh SK,Clarke ID,Terasaki M,et al.Identification of a cancer stem cell in human brain tumors.Cancer Res,2003,63(18):5821-5828
[11]Hemmati HD,Nakano I,Lazareff JA,et al.Cancerous stem cells can arise from pediatric brain tumors.Proc Natl Acad Sci U S A,2003,100(25):15178-15183
[12]Kondo T,Setoguchi T,Taga T.Persistence of a small subpopulation of cancer stem2like cells in the C6 glioma cell line.Proc NallAcad SciUSA,2004,101:781-786.
[13]Kim C F,Jaekson E L,Woolfenden A E,et al.Identification of bronchioalveolar stem cells in normal lung and lung cancer.Cell.2005,121(6):823 - 835.
[14]CollinsAT,Berry PA,Hyde C,et al.Prospective identification of tumorigenic p rostate cancer stem cells. Cancer Res, 2005, 65 : 10946-10951.
[15] Seigel GM, Campbell LM, Narayan M, et al. Evidence for cancer stem cells in retinoblastoma. Mol Vis, 2005, 11:729-732.
[16] Heidt DG, Li C, Mollenberg N, et al. Identification of pancreatic cancer stem cells. J Surg Res, 2006,130 :194 -195.
[17] Varnum-Finney B, Xu L, Brashem-Stein C, et al. Pluripotent,cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat. Med, 2000, 6: 1278-1281.
[18] Lee HY, Kleber M, Hari L, et al.Instructive role of Wnt/beta-catenin in sensory fate specification in neural crest stem cells. Science ,2004,303: 1020-1023
[19] Bhardwaj G, Murdoch B, Wu D, et al.Sonic hedgehog induces the proliferationof primitive human hematopoietic cells via BMP regulation. Nat. Immunol,2001, 2: 172-180
[20] Holland, EC. Gliomagenesis: genetic alterations and mouse models. Nat Rev Genet, 2001,2(2): 120-129
[21] Jamieson, C. H. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N. Engl. J. Med. 2004,351,657-667.
[22] Bachoo RM, Maher EA, Ligon KL, et al. Epidermal growth factor receptor and Ink4a/Arf. Convergent mechanisms governing terminal differentiation and transfer- mation along the neural stem cell to astrocyte axis. Cancer Cell. 2002, 1:269-277.
[23] Goodell MA, Brose K, Paradis G, et al. Isolation and functional properties of murine hematopoietic stem cell that are replicating in vivo. J Exp Med, 1996, 183 (4): 1797-1806.
[24] Wang J, Guo LP, Chen LZ, et al. Identification of cancer stem cell-like side population in human nasopharyngeal carcinoma cell line. Cancer Res. 2007,67(8): 3716-3724.
[25] Hirschmann-Jax C, Foster AE, Wulf GG, et al. A distinct "side population" of cells with high drug efflux capacity in human tumor cells. PNAS. 2004, 101: 14228-14233.
[26] Scharenberg, C. W., Harkey, M. A. & Torok-Storb, B. TheABCG2 transporter is an efficient Hoechst 33342 effluxpump and is preferentially expressed by immature humanhematopoietic progenitors. Blood 2002,99:507-512.
[27] Gottesman, M. M., Fojo, T. & Bates, S. E. Multidrug resistance in cancer: role of ATP-dependent transporters.Nature Rev. Cancer.2002,2,48-58.
[28] Dean M., Rzhetsky A.,Allikmets R. The human ATPbinding cassette (ABC) transporter superfamily. Genome Res.2001,11,1156-1166.
[29] Zhou, S., Zong, Y., Lu, T., et al. Hematopoietic cells from mice that are deficient in both Bcrpl/Abcg2 and Mdr1a/1b develop normally but are sensitized tomitoxantrone. Biotechniques 2003,35:1248-1252.
[30] Islam MO, Kanemura Y, Tajria J, et al. Characterization of ABC transporter ABCB1 expressed in human neural stem /progenitor cells. FEBS Lett, 2005, 579: 3473- 3480.
[31] de Fiqueiredo-Pontes LL, Pintao MC, Oliveira LC, et al. Determination of P-glycoprotein, MDR-related protein 1, breast cancer resistance protein, and lung-resistance protein expression in leukemic stem cells of acute myeloid leukemia.Cytometry B Clin Cytom.2008, [ahead of print].
[32] Krishnamurthy P , Schuetz JD. Role of ABCG2/ BCRP in Biology. Annu Rev Pharmacol Toxicol. 2006 ,46 :381 - 410.
[33] Doyle LA , Yang W, Abruzzo LV , et al . A multidrug resistance transporter from human MCF27 breast cancer cells .Proc Natl Acad Sci USA ,1998 , 95 (26): 15665 -15670.
[34] Maliepaard M, Scheffer GL , Faneyte IF , et al. Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res, 2001,61(8) :3458 - 3464.
[35] Isternino S , Mercier C, Bourasset F , et al. Expression , up-regulation , and transport activity of the multidrug-resistance protein Abcg2 at the mouse blood-brain barrier . Cancer Res , 2004 ,64(9) :3296 - 3301.
[36] Fetsch PA , Abati A , Litman T, et al. Localization of the ABCG2 mitoxantrone resistance-associated protein in normal tissues. Cancer Lett,2006,235(1) :84 - 92.
[37] Diestra J E , Scheffer GL , Catala I , et al . Frequent expression of the multi2drug resistance2associated protein BCRP/ MXR/ ABCP/ ABCG2 in human tumours detected by the BXP221 monoclonal antibody in paraffin2embedded material. J Pathol ,2002 , 198 (2): 213 - 219.
[38] Jonker JW, Smit JW, Brinkhuis RF , et al . Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J Natl Cancer Inst, 2000 , 92 (20): 1651 -1656.
[39] Kruijtzer CM , Beijnen J H , Rosing H , et al. Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918 . J Clin Oncol ,2002 ,20 (13) :2943 - 2950.
[40] Mitomo H , Kato R , Ito A , et al. A functional study on poly-morphism of the ATP-binding cassette transporter ABCG2 : critical role of arginine2482 in methotre- xate transport. BiochemJ , 2003 , 373 (Pt 3): 767 - 774.
[41] Robey RW, Honjo Y, Morisaki K, et al . Mutations at aminoacid 482 in the ABCG2 gene affect substrate and antagonist specificity. Br J Cancer ,2003 , 89 (10):1971 -1978.
[42] Zhou S , Morris JJ , Barnes Y, et al. Bcrp1 gene expression is required for nomal numbers of side population stem cell in mice ,and confers relative protection to mitoxantrone in hematopoietic cells in vivo . PNAS ,2002 ,99(19) : 12339 -12344.
[43] Zhou S , Schuetz JD , Bunting KD , et al. The ABC transporter Bcrp1/ ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype[J ]. Nat Med, 2001 ,7(9): 1028 -1034.
[44] Uchida N, Dykstra B, Lyons K, et al. ABC transporter activities of murine hematopoietic stem cells vary according totheir developmental and activation status. Blood, 2004,103 : 4487-4495.
[45] Doyle LA , Ross DD. Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2).Oncogene ,2003 ,22(47) :7340 - 7358.
[46] Liu G, Yuan XP, Zeng ZH. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Molecular Cancer,2006,5:67.
[47] Kitada S, Pedersen IM, Schimmer AD, et al. Dysregulation of apoptosis genes in hematopoietic malignancies. Oncogene 2002, 21:3459-3474.
[48] Schimmer AD: Inhibitor of apoptosis proteins: translating basic knowledge into clinical practice.Cancer Res 2004,64:7183-7190.
[49]Adams JM,Cory s.The Bcl - 2 protein family:arbiters of cell survival.Seienci,1998,281:1322- 1326.
[50]Safatle - Ribeiro AV,Ribeiro U J r,Corbett CE,et al.Prognostic value of immunohistochemistry in gastric neuroendocrine(carcinoid)tumors.Eur J Gastroenterol Hepatol,2007,19(1):21.
[51]任勇,仲召阳,陈寿松,等.大肠腺瘤及腺癌细胞凋亡与p53和bcl-2的表达.华南国防医学杂志,2005,19(5):11.
[52]赵松,段惠军,齐凤英,等.Bcl-2、p53在皮肤肿瘤中的表达及意义.肿瘤研究与临床,2005,17(3):161.
[53]Zavrides H,Zizi - sermpetzoglou A,Elemenoglou I,et,al.Immunohistochemical express of bcl - 2 in UICC stage Ⅰ and Ⅲ colorectal carcinoma patients:correla- tion with c - erbB - 2,p53,ki - 67,CD44,laminin and collagen Ⅳ in evaluating prognostic singnificance.Pol J Pathl,2006,57(3):149.
[54]宋兰云,王学文,胡晓丽,等.凋亡相关bcl-2基因族在儿童神经母细胞瘤中的表达.Tanjin Med J.2005,33(1):20.
[55]Andreeff M,Jiang S,Zhang X,et al.Expression of Bcl-2-related genes in normal and AML progenitors:changes induced by chemotherapy and retinoic acid.Leukemia 1999,13:1881-1892.
[56]Lu Z,Wu Z,Mo Y.Regulation of Bcl-2 expression by Ubc9.Exp cell Res.2006,312:1865-1875.
[57]Weller M,Malipiero U,Aguzzi A,et al.Protooncogene bcl-2 Gne transfer abrogates Fas/APO-1 antibody-mediated apoptosis of human malignant glioma cells and confers resistance to chemotherapeutic drugs and therapeutic irradiation.J Clin Invest.1995,95:2633-2643
[58]Wei L,Cui L,Snider J,Rivkin M.et al.Transplantation of embryonic stem cells overexpressing Bcl-2 promotes functional recovery after transient cerebral ischemia.Neurobiol Dis.2005,19:183-193
[59]Shman TV,Fedasenka UU,Savitski VP,et al.CD34+ leukemic subpopulation predominantly displays lower spontaneous apoptosis and has higher expression levels of Bcl-2 and MDR1 genes than CD34- cells in childhood AML.Ann Hematol.2008,[ahead of print]
[60]Shman TV,Savitski VP,Fedasenka UU,et al.Apoptosis and proliferation differences between CD34+ and CD34- leukemic subpopulations in childhood acute leukemia.Hematology.2007,[ahead of print]
[61]欧扬,郭秀丽.肿瘤干细胞及其耐药机制.生理科学进展.2007,38(2):115-119.
[62]房佰俊,宋永平,魏旭东,等.慢性粒细胞性白血病干细胞抗伊马替尼机制的初步研究.第一届国际肿瘤干细胞学术会议论文集.杭州,2007,85.
[63]Grinstein E,Wemet P.Cellular signaling in normal and cancerous stem cells.Cell Signal.2007,19(12):2428-2433.
[64]Lessard J,Sauvageau G.Bmi21 determines the proliferative capacity of normal and leukacmic stem cells.Nature,2003,423:255-260.
[65]Cotsarelis,G.& Millar,S.E.Towards a molecular understanding of hair loss and its treatment.Trends Mol.Med.2001,7:293-301.
[66]Burger,H.et al.Imatinib mesylate(STI571)is a substrate for the breast cancer resistance protein(BCRP)/ABCG2 drug pump.Blood.2004,104:2940-2942.
[67]Hofmann,W.K.et al.Presence of the BCR-ABL mutation Glu255Lys prior to STI571(imatinib)treatment in patients with Ph+ acute lymphoblastic leukemia.Blood.2003,102:659-661.
[68]Goldie,J.H.& Coldman,A.J.A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate.Cancer Treat.Rep.1979,63:1727-1733.
[69]Bakker,M.et al.99mTc-Sestamibi scanning with SDZ PSC833 as a functional detection method for resistance modulation in patients with solid tumours.AntiCancer Res.1999,19:2349-2353.
[70]Bates,S.E.et al.A phase Ⅰ/Ⅱ study of infusional vinblastine with the P-glyco-protein antagonist valspodar(PSC 833)renal cell carcinoma.Clin.Cancer Res.2004,10:4724-4733.
[71]Allen,J.D.et al.Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C.Mol.Cancer Ther.2002,1:417-425.
[72] Varnum-Finney B, Xu L, Brashem-Stein C, et al. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat. Med,2000,6: 1278-1281
[73] Lee HY, Kleber M, Hari L, et al.Instructive role of Wnt/beta-catenin in sensory fate specification in neural crest stem cells. Science ,2004,303: 1020-1023
[74] Bhardwaj G, Murdoch B, Wu D, et al.Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation. Nat. Immunol,2001,2:172-180
[75] Yilmaz OH, Valdez R, Theisen BK, et al. Pten dependence distinguishes hematopoietic stem cells from leukaemia-initiating cells. Nature , 2006, 441 (25):475-482.
[76] Ohno R, Asou N, Ohnishi K. Treatment of acute promyelocytic leukemia: strategy toward further increase of cure rate. Leukemia,2003,17:1454-1463.
[77] Aguado T, Carracedo A, Julien B, et al. Cannabinoids induceglioma stem-like cell differentiation and inhibitgliomagenesis. J Biol Chem, 2007, 2: [ahead of print].
[78] Feuring BM, Frankel A, Gerhard B, et al. Variable cytotoxicity of diphtheria toxin 388 granulocyte macro2phage colony stimulating factor fusion protein for acute myelogenous leukemia stem cells. Exp Hematol, 2000, 28:1390-1400.
[79] Altundag K, Altundag O, Elkiran ET, et al. Addition of granulocytecolony stimulating factor ( G-CSF) to adjuvant treatment may increase survival in patients with operable breast cancer cells: interaction of G-CSF with dormant micrometastatic breast cancer cells. Med Hypotheses, 2004,63:56-58.
[80] Schatzlein AG. Delivering cancer stem cell therapies-A rolefor nanomedicines. Euro J Cancer, 2006,42:1309-1315.
[2]Bonnet D,Dick JE.Human acute myeloid leukemia is organized as a hierarchy thatoriginates from a primitive hematopoietic cell.Nat Med,1997,3(7):730-737
[3]Al-Hajj M,Wicha MS,Benito-Hemandez A,et al.Prospective identification of tumorigenic breast cancer cells.Proc Natl Acad Sci U S A,2003,100(7):3983-3988
[4]Singh SK,Clarke ID,Terasaki M,et al.Identification of a cancer stem cell in human brain tumors.Cancer Res,2003,63(18):5821-5828
[5]Hemmati HD,Nakano I,Lazareff JA,et al.Cancerous stem cells can arise from pediatric brain tumors.Proc Natl Acad Sci U S A,2003,100(25):15178-15183
[6]Kondo T,Setoguchi T,Taga T.et al.Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line.Proc Natl Acad Sci U S A,2004,101(3):781-786
[7]Yuan X,Curtin J,Xiong Y,et al.Isolation of cancer stem cells from adult glioblastoma multiforme.Oncogene,2004,23(58):9392-9400
[8]方加胜,邓永文,李茗初,等.神经上皮来源脑肿瘤中肿瘤干细胞的分离培养与鉴定.中华医学杂志,2007,87:298-303.
[9]李茗初,邓永文,伍军,等.髓母细胞瘤中脑肿瘤干细胞的分离培养及鉴定.癌症.2006,25(2):241-246.
[10]Kim C F,Jackson E L,Woolfenden A E,et al.Identification of bronchioalveolar stem cells in normal lung and lung cancer.Cell.2005,121(6):823 - 835.
[11]CollinsAT,Berry PA,Hyde C,et al.Prospective identification of tumorigenic p rostate cancer stem cells.Cancer Res,2005,65:10946- 10951.
[12]Heidt DG,Li C,Mollenberg N,et al.Identification of pancreatic cancer stem cells.J Surg Res,2006,130:194 -195.
[13]Reya T,Morrison SJ,Clarke MF,et al.Stem cells,cancer,and cancer stem cells.Nature,2001,414(6859):105-111
[14]Soltysova A,Altanerova V,Altaner C.Cancer stem cells.Neoplasma,2005,52 (6):435-440.
[15]Dean M,Fojo T,Bates S.Tumour stem cells and drug resistance.Nat Rev Cancer 2005,5:275-284.
[16]Chen L,Shervington A.Chemoresistance in gliomas.Mol Cell Biochem.2008,
[17]Eramo A,Vitiani LR,Zeuner A,et al.Chemotherapy resistance of glioblastoma stem cells.Cell Death and Differentiation.2006,13:1238-1241.
[18]Raaijmakers M,de Grouw E,Heuver L,et al.Breast cancer resistance protein in drug resistance of primitive CD34+CD38-cells in acute myeloid leukemia.Clinical cancer research.2005.11:2436-2444.
[19]宋永平,房佰俊,魏旭东,等.K562/Vp16细胞系中边缘细胞对伊马替尼耐药机制的初步研究.2005,26(11):669-673.
[20]Clevers H.Stem cells,asymmetric division and cancer.Nature.2005,37:1027-1028.
[21]Galli R,Gritti A,Bonfanti L,et al.Neural stem cells:an overview.Circ Res,2003,92(6):598-608
[22]Berger F,Gay E,Pelletier L,et al.Development of gliomas:potential role of asymmetrical cell division of neural stem cells.Lancet Oncol,2004,5(8):511-514.
[23]Nish H,Nishimura S,Higashiura M,et al.A new method for histamine release from purified peripheral blood basophils using monoclonal antibody-coated magnetic beads.J Immunol Methods,2000,240(1-2):39-46.
[24]Siegel D L.Selecting antibodies to cell surface antigens usingrnagnetic sorting techniques.MethodsMol Biol,2002,178:219 - 226.
[25]Miraglia S,Godfrey W,Yin AH,et al.A novel five-transmembrane hematopoietic stem cell antigen:isolation,characterization,and molecular cloning.Blood,1997,90(12):5013-5021
[26]Uchida N,Buck DW,He DP,et al.Direct isolation of human central nervous system stem cells.Proc Natl Acad Sci,2000,97(26):14720-14725
[27]Vescovi LA,Galli R,Reynolds BA.Brain tumor stem cells.Nature Reviews,2006,6:425-436.
[28]司徒镇强,吴军正主编.细胞培养.北京:世界图书出版公司,1996:244-245.
[29]Lal S,Lacrolx M,Tofilon P,et al.An implantable guide-screw system for brain tumor studies in small animals.J Neurosurg,2000,92:326-333.
[30]Lassman AB.Molecular biology of gliomas.Curr Neurol Neurosci Rep,2004,4(3):228-233.
[31]刘艳辉,毛伯镛,姜曙等.髓母细胞瘤中表皮生长因子受体的表达及基因扩增分析.中华神经外科疾病研究杂志,2002,1(1):51-53
[32]Ueba T,Takahashi JA,Fukumoto M,et al.Expression of fibroblast growth factor receptor-1 in human glioma and meningioma tissues.Neurosurgery,1994,34(2):221-225.
[33]Duplan SM,Theoret Y,Kenigsberg RL.Antitumor activity of fibroblast growth factors(FGFs)for medulloblastoma may correlate with FGF receptor expression and tumor variant.Clin Cancer Res,2002,8(1):246-257.
[34]Aold T,Kato S,Fox JC et al.Inhibition of autocrine fibroblast growth factor signaling by the adenovirus-mediated expression of an antisense transgene or a dominant negative receptor in human glioma cells in vitro.Int.J.Oncol.2002,21(3):629-636.
[35]Holland,EC,Hivelv WP,Depinho RA,et al.A constitutively active epidermal growth factor receptor cooperates with disruption of G1 cell-cycle arrest pathways to induce glioma-like lesions in mice.Genes Dev.1998,12(23):3675-3685.
[36]Holland,EC.Progenitor cells and glioma formation.Curr.Opin.Neurol.2001,14(6):683-688.
[37]Tropepe V,Sibilia M,Cinma BG,et al.Distinct Neural Stem Cells Proliferate in Response to EGF and FGF in the Developing Mouse Telencephalon.Dev Biol,1999,208(1):166-188
[38]Sigh SK,Hawkins C,Clarke ID,et al.Identification of human brain tumor initiating cells.Nature.2004,432:396-401.
[39]凌诒萍主编.细胞生物学.北京:人民卫生出版社,2001.121-128
[40]Miraglia S,Godfrey W,Yin AH,et al.A novel five-transmembrane hematopoietic stem cell antigen:isolation,characterization,and molecular cloning.Blood,1997,90(12):5013-5021
[41]Vescovi AL,Snyder EY.Establishment and properties of neural stem cell clones:plasticity in vitro and in vivo.Brain Pathol,1999,9(3):569-598.
[42]Tanja Z,Paul RS,Juan RS,et al.Neural Stem Cells-Methods and Protocols.Totowa,New Jersey,USA..Humana Press Inc,2002.149-297
[43]Jeong SW,Chu K,Jung KH,et al.Human neural stem cell transplantation promotes functional recovery in rats with experimental intracerebral hemorrhage.Stroke,2003,34(9):2258-2263
[44]Kilpatrick TJ,Bartlett PF.Cloning and growth of multipotential neural precursors:requirements for proliferation and differentiation.Neuron,1993,10(2):255-265
[45]Gritti A,Rosati B,Lecchi M,et al.Excitable properties in astrocytes derived from human embryonic CNS stem cells.Eur J Neurosci,2000,12(10):3549-3559
[46]Gage FH.Mammalian neural stem cells.Science,2000,287(5457):1433-1438
[47]Galli R,Binda E,Orfanelli U,et al.Isolation and characterization of tumorigenic,stem-like neural precursors from human glioblastoma.Cancer Res,2004,64(19):7011-7021
[48]Ignatova TN,Kukekov VG.,Laywell ED,et al.Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro.Glia,2002,39(3):193-206
[49]余爽,张京钟,张海燕等.免疫磁珠体外纯化人胎脑中CD133阳性干细胞的实验研究.神经解剖学杂志,2004,20(3):271-274
[50]Goodell MA,Brose K,Paradis G,et al.Isolation and functional properties of murine hematopoietic stem cell that are replicating in vivo.J Exp Med,1996,183(4):1797-1806.
[51]王红晖,聂捷林,李莹辉,等.成体干细胞中的SP细胞群.中国生物工程杂志,2005,25(12):75-78.
[52]Lubna P,Tammy C,Robin S,et al.Side population is enriched in tumorigenic,stem-like cancer cells,whereas ABCG2+ and ABCG2- cancer cells are similar tumorigenic.Cancer Res,2005,65(14):6207-6219.
[53]Hirschmann-Jax C,Foster AE,Wulf GG,et al.A distinct "side population" of cells with high drag effiux capacity in human tumor cells.PNAS,2004,101:14228- 14233.
[54]Naotsugu H,Tohru U,Hiroshi I,et al.Characerization of a side population of cancer cells from human gasterointestinal system.Stem Cells,2006,24:506-513.
[55]张卓然.实用细胞培养技术[M].北京:人民卫生出版社.1999.97.
[56]J Kurz Eu,Leader KB,Krol DJ,et al.Modulation of human DNA topoisomerase Iialpha funtion by interaction with 14-3-3epsilon.J Biol Chem,2000,275(18):13948 -13954.
[57]Zaman GJ,Versantvoort CH,Smit JJ,et al.Analysis of the expression of MRP,the gene for a new putative transmembrane drug transporter,in human multidrug resistant lung cancer cell lines[J].Cancer Res,1993,53(8):1747-1750.
[58]吕辉.BCRP表达调节及运用RNA干扰技术逆转其介导的肿瘤多药耐药研究.[硕士学位论文].长沙:中南大学,2005.
[59]Yamaue H,Tanimura H,Tsunoda T,et al.Cheosensitivity testing with highly pughly purified fresh human tumor cells with the MTT olorimetric assay.Eur J Canoe,1991,27(10):1258-1263.
[60]Liu G,Yuan XP,Zeng ZH:Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma.Molecular Cancer,2006,5:67.
[61]Yin D,Xie D,Hofmann WK,et al.DNA repair gene 06 -methylguanine - DNA methyltransferase:promoter hypermethylation associated with decreased expression and G:C to A:T mutations of p53 in brain tumors.Mol Carcinog.2003,36(1):23.
[62]Nagane M,Asai A,Shibui S,et al.Expression pattern of chemoresistance related for proper selection of anticancer drugs.Jpa J Clin Oncol,1999,29(1):527.
[63]胡苹,左焕琮,马雄君,等.06甲基鸟嘌呤DNA转移酶在神经胶质瘤中的表达及其与亚硝脲耐药的关系.中日友好医院学报,2003,17(4):216.
[64]Scharenberg,C.W.,Harkey,M.A.& Torok-Storb,B.TheABCG2 transporter is an efficient Hoechst 33342 effiux pump and is preferentially expressed by immature humanhematopoietic progenitors.Blood 2002,99:507-512.
[65]Gottesman,M.M.,Fojo,T.& Bates,S.E.Multidrug resistance in cancer:role of ATP-dependent transporters .Nature Rev. Cancer.2002, 2,48-58.
[66] Dean M., Rzhetsky A.,Allikmets R. The human ATPbinding cassette (ABC) transporter superfamily. Genome Res.2001,11,1156-1166.
[67] Zhou, S., Zong, Y., Lu, T., et al. Hematopoietic cells from mice that are deficient in both Bcrp1/Abcg2 and Mdr1a/1b develop normally but are sensitized tomitoxantrone. Biotechniques 2003,35:1248-1252.
[68] Lin JH , Yamazaki M. Clinical relevance of P-glycoprotein in drugtherapy . Drug Metab Rev, 2003 , 35 (4) :417- 454.
[69] Haimeur A , Conseil G, Deeley RG, et al . The MRP2related and BCRP/ABCG2 multidrug resistance proteins : biology , substrate specificity and . regulation. Curr Drug Metab, 2004, 5(1) :21-53.
[70] Doyle LA , Yang W, Abruzzo LV , et al . A multidrug resistance transporter from human MCF-7 breast cancer cells .Proc Natl Acad Sci USA ,1998 , 95 (26): 15665 -15670.
[71] Altenberg GA. Structure of multidrug-resistance proteins of the ATP-binding cassette(ABC) superfamily. Curr med chem-Anti cancer angents. 2004,4:53-62.
[72] Kage K, Tsukahara S , Sugiyama T , et al . Dominant negative inhibition of breast cancer resistance protein as drug efflux pump through the inhibition of S2S dependent homodimerization. Int J Cancer, 2002 , 97 (5) :626 - 630.
[73] Islam MO, Kanemura Y, Tajria J, et al. Characterization of ABC transporter ABCB1 expressed in human neural stem /progenitor cells. FEBS Lett, 2005, 579: 3473-3480.
[74] Krishnamurthy P , Schuetz JD. Role of ABCG2/ BCRP in Biology. Annu Rev Pharmacol Toxicol. 2006 ,46 :381 - 410.
[75] Zhou S , Morris JJ , Barnes Y, et al. Bcrp1 gene expression is required for nomal numbers of side population stem cell in mice ,and confers relative protection to mitoxantrone in hematopoietic cells in vivo . PNAS ,2002 ,99(19) : 12339 -12344.
[76] Zhou S , Schuetz JD , Bunting KD , et al. The ABC transporter Bcrp1/ ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med, 2001 ,7(9): 1028 -1034.
[77]de Fiqueiredo-Pontes LL,Pintao MC,Oliveira LC,et al.Determination of P-glycoprotein,MDR-related protein 1,breast cancer resistance protein,and lung-resistance protein expression in leukemic stem cells of acute myeloid leukemia.Cytometry B Clin Cytom.2008,[ahead of print].
[78]Kitada S,Pedersen IM,Schimmer AD,et al.Dysregulation of apoptosis genes in hematopoietic malignancies.Oncogene 2002,21:3459-3474.
[79]Schimmer AD:Inhibitor of apoptosis proteins:translating basic knowledge into clinical practice.Cancer Res 2004,64:7183-7190.
[80]Safatle - Ribeiro AV,Ribeiro U J r,Corbett CE,et al.Prognostic value of immunohistochemistry in gastric neuroendocrine(carcinoid)tumors.Eur J Gastroenterol Hepatol,2007,19(1):21.
[81]任勇,仲召阳,陈寿松,等.大肠腺瘤及腺癌细胞凋亡与p53和bcl-2的表达.华南国防医学杂志,2005,19(5):11.
[82]赵松,段惠军,齐凤英,等.Bcl-2、p53在皮肤肿瘤中的表达及意义.肿瘤研究与临床,2005,17(3):161.
[83]Zavrides H,Zizi - sermpetzoglou A,Elemenoglou I,et,al.Immunohistochem-ical express of bcl - 2 in UICC stage Ⅰ and Ⅲ colorectal carcinoma patients:correla- tion with c - erbB - 2,p53,ki - 67,CD44,laminin and collagen Ⅳ in evaluating prognostic singnificance.Pol J Pathl,2006,57(3):149.
[84]宋兰云,王学文,胡晓丽,等.凋亡相关bcl-2基因族在儿童神经母细胞瘤中的表达.Tanjin Med J.2005,33(1):20.
[85]Andreeff M,Jiang S,Zhang X,et al.Expression of Bcl-2-related genes in normal and AML progenitors:changes induced by chemotherapy and retinoic acid.Leukemia 1999,13:1881-1892.
[86]Lu Z,Wu Z,Mo Y.Regulation of Bcl-2 expression by Ubc9.Exp cell Res.2006,312:1865-1875.
[87]Weller M,Malipiero U,Aguzzi A,et al.Protooncogene bcl-2 Gne transfer abrogates Fas/APO-1 antibody-mediated apoptosis of human malignant glioma cells and confers resistance to chemotherapeutic drugs and therapeutic irradiation.J Clin Invest.1995,95:2633-2643
[88]Wei L,Cui L,Snider J,Rivkin M.et al.Transplantation of embryonic stem cells overexpressing Bcl-2 promotes functional recovery after transient cerebral ischemia.Neurobiol Dis.2005,19:183-193
[89]房佰俊,宋永平,魏旭东,等.慢性粒细胞性白血病干细胞抗伊马替尼机制的初步研究.第一届国际肿瘤干细胞学术会议论文集.杭州,2007,85.
[1]黄文清编著.神经肿瘤病理学.北京:军事医学科学出版社,2001.41-54.
[2]Reya T,Morrison SJ,Clarke MF,et al.Stem cells,cancer,and cancer stem cells.Nature,2001,414(6859):105-111.
[3]Recht L,Jang T,Savarese T,et al.Neural stem cells and neuro-oncology:Quo vadis? J Cell Biochem,2003;88(1):11-19.
[4]Lapidot T,Sirard C,Vormoor J,et al.A cell initiating human acute myeloid leukaemia after transplantation into SCID mice.Nature,1994,367(6464):645-648
[5]Bonnet D,Dick JE.Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell.Nat Med,1997,3(7):730-737
[6]Al-Hajj M,Wicha MS,Benito-Hernandez A,et al.Prospective identification of tumorigenic breast cancer cells.Proc Natl Acad Sci U S A,2003,100(7):3983-3988
[7]Ignatova TN,Kukekov VG.,Laywell ED,et al.Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro.Glib,2002,39(3):193-206
[8]Singh SK,Clarke ID,Terasaki M,et al.Identification of a cancer stem cell in human brain tumors.Cancer Res,2003,63(18):5821-5828
[9]Hemmati HD,Nakano I,Lazareff JA,et al.Cancerous stem cells can arise from pediatric brain tumors.Proc Natl Acad Sci U S A,2003,100(25):15178-15183
[10]Kondo T,Setoguchi T,Taga T.et al.Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line.Proc Natl Acad Sci U S A,2004,101(3):781-786
[11]Singh SK,Hawkins C,Clarke ID,et al.Identification of human brain tumour initiating cells.Nature,2004,432(7015):396-401
[12]Yuan X,Curtin J,Xiong Y,et al.Isolation of cancer stem cells from adult glioblastoma multiforme.Oncogene,2004,23(58):9392-9400
[13]Galli R,Binda E,Orfanelli U,et al.Isolation and characterization of tumorigenic,stem-like neural precursors from human glioblastoma.Cancer Res,2004,64(19):7011-7021
[14]李茗初,陈风华,邓永文等.悬浮法培养C6胶质瘤细胞系和该细胞系中脑肿瘤干细胞的分离.中国现代医学杂志,2004,14(24):57-60
[15]方加胜,邓永文,李茗初,等.神经上皮来源脑肿瘤中肿瘤干细胞的分离培养与鉴定.中华医学杂志,2007,87:298-303.
[16]李茗初,邓永文,伍军,等.髓母细胞瘤中脑肿瘤干细胞的分离培养及鉴定.癌症.2006,25(2):241-246.
[17]Vescovi LA,Galli R,Reynolds BA.Brain tumor stem cells.Nature Reviews,2006,6:425-436.
[18]Hamburger AW,Salmon SE.Primary bioassay of human tumor stem cells.Science,1977,197(4302):461-463
[19]Rosenblum ML,Gerosa MA,Wilson CB,et al.Stem cell studies of human malignant brain tumors.Part 1:Development of the stem cell assay and its potential.J Neurosurg,1983,58(2):170-176.
[20]巢卫,彭祥鄂.人体肿瘤干细胞软琼脂集落培养-Ⅱ双层琼脂法.癌症,1987,6(01):30-33+89
[21]Suslov ON,Kukekov VG,Ignatova TN and Steindler DA.Neural stemcell heterogeneity demonstrated by molecular phenotyping of clonalneurospheres.Proc.Natl.Acad.Sci.USA.2002 99:14506-14511
[22]]Nish H,Nishimura S,Higashiura M,et al.A new method for histamine release from purified peripheral blood basophils using monoclonal antibody-coated magnetic beads.J Immunol Methods,2000,240(1-2):39-46.
[23]Goodell MA,Brose K,Paradis G,et al.Isolation and functional properties of murine hematopoietic stem cell that are replicating in vivo.J Exp Med,1996,183(4):1797-1806.
[24]Galli R,Gritti A,Bonfanti L,et al.Neural stem cells:an overview.Circ Res,2003,92(6):598-608
[25] Lin H, Schagat T. Neuroblasts: a model for the asymmetric division of stem cells. Trends Genet,1997,13(1):33-39
[26] Kilpatrick TJ, Bartlett PF. Cloning and growth of multipotential neural precursors: requirements for proliferation and differentiation. Neuron, 1993, 10(2): 255-265
[27] Gritti A, Rosati B, Lecchi M, et al. Excitable properties in astrocytes derived from human embryonic CNS stem cells. Eur J Neurosci, 2000, 12(10):3549-3559
[28] Gage FH. Mammalian neural stem cells. Science, 2000,287(5457):1433-1438
[29] Miraglia S, Godfrey W, Yin AH, et al. A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and .molecular cloning. Blood, 1997, 90(12):5013-5021
[30] Galderisi U, Cipollaro M, Giordano A. Stem cells and brain cancer. Cell Death and Differentiation,2006,13:5-11.
[31] Almqvist PM, Mah R, Lendahl U,et al. Immunohistochemical detection of nestin in pediatric brain tumors. Histochem. Cytochem.2002, 50: 147-158
[32] Wang J, Guo LP, Chen LZ, et al. Identification of cancer stem cell-like side population in human nasopharyngeal carcinoma cell line. Cancer Res. 2007,67(8): 3716-3724.
[33] 曾益新主编．肿瘤学．北京：人民卫生出版社,2003．11—236
[34] Holland, EC. Gliomagenesis: genetic alterations and mouse models. Nat Rev Genet, 2001,2(2): 120-129
[35] Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer.Nat Rev Cancer, 2003, 3(12):895-902
[36] Mondal D, Pradhan L, LaRussa VF. Signal transduction pathways involved in the lineage-differentiation of NSCs: can the knowledge gained from blood be used in the brain? Cancer Invest, 2004,22(6): 925-943
[37] Varnum-Finney B, Xu L, Brashem-Stein C, et al. Pluripotent,cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat. Med,2000, 6: 1278-1281
[38] Lee HY, Kleber M, Hari L, et al.Instructive role of Wnt/beta-catenin in sensory fate specification in neural crest stem cells. Science ,2004,303: 1020-1023
[39] Bhardwaj G, Murdoch B, Wu D, et al.Sonic hedgehog induces the proliferationof primitive human hematopoietic cells via BMP regulation. Nat. Immunol,2001, 2:172-180
[40] Ruiz i Altaba A, Sanchez P and Dahmane N.Gli and hedgehog in cancer: tumours, embryos and stem cells. Nat. Rev. Cancer,2002,2: 361-372
[41] Brivanlou AH and Darnell Jr JE. Signal transduction and the control of gene expression. Science ,2002,295: 813-818
[42] Wechsler-Reya RJ and Scott MP .Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Neuron ,1999,22: 103-114
[43] Machold R, Hayashi S, Rutlin M, et al. Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches. Neuron,2003, 39: 937-950
[44] Rao G, Pedone CA, Valle LD, et al. Sonic hedgehog and insulin-like growth factor signaling synergize to induce medulloblastoma formation from nestin-expressing neural progenitors inmice. Oncogene,2004, 23: 6156-6162
[45] Pietsch T, Taylor MD and Rutka JT .Molecular pathogenesis of childhood brain tumors. J. Neurooncol. 2004,70: 203-215
[46] Das AV, James J, Zhao X, et al.Identification of c-Kit receptor as a regulator of adult neural stem cells in the mammalian eye: interactions with Notch signaling. Dev. Biol,2004,273: 87-105
[47] Hitoshi S, Seaberg RM, Koscik C, et al. Primitive neural stem cells from the mammalian epiblast differentiate to definitive neural stem cells under the control of Notch signaling. Genes Dev.2004,18: 1806-1811
[48] Joutel A,Tournier-Lasserve E. Notch signalling pathway and human diseases. Semin.Cell.Dev.Biol, 1998,9(6):619-25。
[49] Fan X, Mikolaenko I, Elhassan I, et al. Notchl and notch2 have opposite effects on embryonal brain tumor growth. Cancer Res,2004,64: 7787-7793
[50] Lee HY, Kleber M, Hari L, et al. Instructive role of Wnt/beta-catenin in sensory fate specification in neural crest stem cells. Science,2004, 303: 1020-1023
[51] Valk-Lingbeek ME, Bruggeman SW and van Lohuizen M . Stem cells and cancer; the polycomb connection. Cell,2004,118: 409-418
[52] Molofsky AV, Pardal R, Iwashita T, et al. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 2003,425: 962-967
[53] Valk-Lingbeek ME, Braggeman SW et al. Stem cells and cancer; the polycomb connection. Cell,2004,118: 409-418
[54] Gentao L, Xiangpeng Y, Zhaohui Z, et al. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in globlastoma. Molecular Cancer,2006,5:67.
[55] Linheng Li ,William B. Neaves. Normal stem cells and cancer stem cells: the niche matters. Cancer Res,2006,66(9):4553-4557.
[56] Uchida K, Mukai M, Okano H, et al. Possible oncogenicity of subventricular zone neural stem cells: case report. Neurosurgery, 2004, 55(4):977-987
[57] Rao G, Pedone CA, Coffin CM, et al. c-Myc enhances sonic hedgehoginduced medulloblastoma formation from nestin-expressing neural progenitors in mice. Neoplasia, 2003, 5(3): 198-204
[58] Almqvist PM, Mah R, Lendahl U, et al.Immunohistochemical detection of nestin in pediatric brain tumors.Histochem. Cytochem.2002, 50: 147-158
[59] Alvarez-Buylla A and Garcia-Verdugo JM .Neurogenesis in adult subventricular zone. Neurosci. 2002,22: 629-634
[60] Sutton LN, Phillips P and Lange B . Midline supratentorial tumors.Neurosurg. Clin. North Am, 1992, 3: 821-837
[61] Pomeroy SL, Tamayo P, Gaasenbeek M, et al. Prediction of central nervous system embryonal tumor outcome based on gene expression[J]. Nature, 2002, 415(6870): 436-442.
[62] Leung C, Lingbeek M, Shakhova O, et al. Bmil is essential for cerebellar development and is overexpressed in human medulloblastoma. Nature, 2004, 428(6980):337-341.
[63] Groszer M, Erickson R, Scripture-Adams DD, et al. Negative regulation of stem cell/progenitor cell proliferation by the PTEN tumor suppressor gene in vivo. Science, 2001, 294(5549):2186- 2189.
[64] Bachoo RM, Maher EA, Ligon KL, et al. Epidermal growth factor receptor and Ink4a/Arf. Convergent mechanisms governing terminal differentiation and transfer- mation along the neural stem cell to astrocyte axis. Cancer Cell. 2002, 1:269-277.
[65] Matsui WH, Huff CA, Wang Q. Characterization of clonogenic multiple myeloma cells. Blood,2004,103:2332-2336.
[66] Yilmaz OH, Valdez R, Theisen BK, et al. Pten dependence distinguishes hematopoietic stem cells from leukaemia-initiating cells. Nature, 2006,441 (25): 475-482.
[67] Chen MF, Lin CT, Chen WC, et al. The sensitivity of human mesenchymal stem cell to ionizing radiation..Int Radiation Oncology Biol Phys, 2006, 66(1):244-253.
[68] Bao S, Wu Q, Mclendon RE, et al. Glioma stem cell promote radioresistance by preferential activation of the DNA damage response. Nature, 2006, 444(7120):756- 760.
[69] Ohno R, Asou N, Ohnishi K.Treatment of acute promyelocytic leukemia: strategy toward further increase of cure rate. Leukemia,2003,17:1454-1463.
[70] Aguado T, Carracedo A, Julien B, et al. Cannabinoids induceglioma stem-like cell differentiation and inhibitgliomagenesis. J Biol Chem, 2007, 2: [ahead of print].
[1]曾益新编著.肿瘤学.北京:人民卫生出版社.2003,366-393.
[2]Reya T,Morrison SJ,Clarke MF,et al.Stem cells,cancer,and cancer stem cells.Nature,2001,414(6859):105-111
[3]Soltysova A,Altanerova V,Altaner C.Cancer stem cells.Neoplasma,2005,52(6):435-440.
[4]Dean M,Fojo T,Bates S.Tumour stem cells and drug resistance.Nat Rev Cancer 2005,5:275-284.
[5]Bruce W R,Van Der Gaag H.A quantitative assay for t he number of murine lymphoma cells capable of proliferation in vivo.Nature,1963,199:79 - 80.
[6]Wodinsky I,Swiniarski J,Kensler C J.Spleen colony studies of leukemia L1210.Ⅳ.Sensitivities of L1210 and L1210/ 6-MP to triazenoimi dazolecarboxamid- es- a preliminary report.Cancer Chemother Rep.1968,52(3):393 - 398.
[7]Hamburger A W,Salmon S E.Primary bioassay of humanturnor stem cells.Science.1977,197(4302):461 - 463.
[8]Bonnet D,Dick JE.Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell.Nat Med,1997,3(7):730-737
[9]Al-Hajj M,Wieha MS,Benito-Hernandez A,et al.Prospective identification of tumorigenic breast cancer cells.Proc Natl Acad Sci U S A,2003,100(7):3983-3988
[10]Singh SK,Clarke ID,Terasaki M,et al.Identification of a cancer stem cell in human brain tumors.Cancer Res,2003,63(18):5821-5828
[11]Hemmati HD,Nakano I,Lazareff JA,et al.Cancerous stem cells can arise from pediatric brain tumors.Proc Natl Acad Sci U S A,2003,100(25):15178-15183
[12]Kondo T,Setoguchi T,Taga T.Persistence of a small subpopulation of cancer stem2like cells in the C6 glioma cell line.Proc NallAcad SciUSA,2004,101:781-786.
[13]Kim C F,Jaekson E L,Woolfenden A E,et al.Identification of bronchioalveolar stem cells in normal lung and lung cancer.Cell.2005,121(6):823 - 835.
[14]CollinsAT,Berry PA,Hyde C,et al.Prospective identification of tumorigenic p rostate cancer stem cells. Cancer Res, 2005, 65 : 10946-10951.
[15] Seigel GM, Campbell LM, Narayan M, et al. Evidence for cancer stem cells in retinoblastoma. Mol Vis, 2005, 11:729-732.
[16] Heidt DG, Li C, Mollenberg N, et al. Identification of pancreatic cancer stem cells. J Surg Res, 2006,130 :194 -195.
[17] Varnum-Finney B, Xu L, Brashem-Stein C, et al. Pluripotent,cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat. Med, 2000, 6: 1278-1281.
[18] Lee HY, Kleber M, Hari L, et al.Instructive role of Wnt/beta-catenin in sensory fate specification in neural crest stem cells. Science ,2004,303: 1020-1023
[19] Bhardwaj G, Murdoch B, Wu D, et al.Sonic hedgehog induces the proliferationof primitive human hematopoietic cells via BMP regulation. Nat. Immunol,2001, 2: 172-180
[20] Holland, EC. Gliomagenesis: genetic alterations and mouse models. Nat Rev Genet, 2001,2(2): 120-129
[21] Jamieson, C. H. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N. Engl. J. Med. 2004,351,657-667.
[22] Bachoo RM, Maher EA, Ligon KL, et al. Epidermal growth factor receptor and Ink4a/Arf. Convergent mechanisms governing terminal differentiation and transfer- mation along the neural stem cell to astrocyte axis. Cancer Cell. 2002, 1:269-277.
[23] Goodell MA, Brose K, Paradis G, et al. Isolation and functional properties of murine hematopoietic stem cell that are replicating in vivo. J Exp Med, 1996, 183 (4): 1797-1806.
[24] Wang J, Guo LP, Chen LZ, et al. Identification of cancer stem cell-like side population in human nasopharyngeal carcinoma cell line. Cancer Res. 2007,67(8): 3716-3724.
[25] Hirschmann-Jax C, Foster AE, Wulf GG, et al. A distinct "side population" of cells with high drug efflux capacity in human tumor cells. PNAS. 2004, 101: 14228-14233.
[26] Scharenberg, C. W., Harkey, M. A. & Torok-Storb, B. TheABCG2 transporter is an efficient Hoechst 33342 effluxpump and is preferentially expressed by immature humanhematopoietic progenitors. Blood 2002,99:507-512.
[27] Gottesman, M. M., Fojo, T. & Bates, S. E. Multidrug resistance in cancer: role of ATP-dependent transporters.Nature Rev. Cancer.2002,2,48-58.
[28] Dean M., Rzhetsky A.,Allikmets R. The human ATPbinding cassette (ABC) transporter superfamily. Genome Res.2001,11,1156-1166.
[29] Zhou, S., Zong, Y., Lu, T., et al. Hematopoietic cells from mice that are deficient in both Bcrpl/Abcg2 and Mdr1a/1b develop normally but are sensitized tomitoxantrone. Biotechniques 2003,35:1248-1252.
[30] Islam MO, Kanemura Y, Tajria J, et al. Characterization of ABC transporter ABCB1 expressed in human neural stem /progenitor cells. FEBS Lett, 2005, 579: 3473- 3480.
[31] de Fiqueiredo-Pontes LL, Pintao MC, Oliveira LC, et al. Determination of P-glycoprotein, MDR-related protein 1, breast cancer resistance protein, and lung-resistance protein expression in leukemic stem cells of acute myeloid leukemia.Cytometry B Clin Cytom.2008, [ahead of print].
[32] Krishnamurthy P , Schuetz JD. Role of ABCG2/ BCRP in Biology. Annu Rev Pharmacol Toxicol. 2006 ,46 :381 - 410.
[33] Doyle LA , Yang W, Abruzzo LV , et al . A multidrug resistance transporter from human MCF27 breast cancer cells .Proc Natl Acad Sci USA ,1998 , 95 (26): 15665 -15670.
[34] Maliepaard M, Scheffer GL , Faneyte IF , et al. Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res, 2001,61(8) :3458 - 3464.
[35] Isternino S , Mercier C, Bourasset F , et al. Expression , up-regulation , and transport activity of the multidrug-resistance protein Abcg2 at the mouse blood-brain barrier . Cancer Res , 2004 ,64(9) :3296 - 3301.
[36] Fetsch PA , Abati A , Litman T, et al. Localization of the ABCG2 mitoxantrone resistance-associated protein in normal tissues. Cancer Lett,2006,235(1) :84 - 92.
[37] Diestra J E , Scheffer GL , Catala I , et al . Frequent expression of the multi2drug resistance2associated protein BCRP/ MXR/ ABCP/ ABCG2 in human tumours detected by the BXP221 monoclonal antibody in paraffin2embedded material. J Pathol ,2002 , 198 (2): 213 - 219.
[38] Jonker JW, Smit JW, Brinkhuis RF , et al . Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J Natl Cancer Inst, 2000 , 92 (20): 1651 -1656.
[39] Kruijtzer CM , Beijnen J H , Rosing H , et al. Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918 . J Clin Oncol ,2002 ,20 (13) :2943 - 2950.
[40] Mitomo H , Kato R , Ito A , et al. A functional study on poly-morphism of the ATP-binding cassette transporter ABCG2 : critical role of arginine2482 in methotre- xate transport. BiochemJ , 2003 , 373 (Pt 3): 767 - 774.
[41] Robey RW, Honjo Y, Morisaki K, et al . Mutations at aminoacid 482 in the ABCG2 gene affect substrate and antagonist specificity. Br J Cancer ,2003 , 89 (10):1971 -1978.
[42] Zhou S , Morris JJ , Barnes Y, et al. Bcrp1 gene expression is required for nomal numbers of side population stem cell in mice ,and confers relative protection to mitoxantrone in hematopoietic cells in vivo . PNAS ,2002 ,99(19) : 12339 -12344.
[43] Zhou S , Schuetz JD , Bunting KD , et al. The ABC transporter Bcrp1/ ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype[J ]. Nat Med, 2001 ,7(9): 1028 -1034.
[44] Uchida N, Dykstra B, Lyons K, et al. ABC transporter activities of murine hematopoietic stem cells vary according totheir developmental and activation status. Blood, 2004,103 : 4487-4495.
[45] Doyle LA , Ross DD. Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2).Oncogene ,2003 ,22(47) :7340 - 7358.
[46] Liu G, Yuan XP, Zeng ZH. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Molecular Cancer,2006,5:67.
[47] Kitada S, Pedersen IM, Schimmer AD, et al. Dysregulation of apoptosis genes in hematopoietic malignancies. Oncogene 2002, 21:3459-3474.
[48] Schimmer AD: Inhibitor of apoptosis proteins: translating basic knowledge into clinical practice.Cancer Res 2004,64:7183-7190.
[49]Adams JM,Cory s.The Bcl - 2 protein family:arbiters of cell survival.Seienci,1998,281:1322- 1326.
[50]Safatle - Ribeiro AV,Ribeiro U J r,Corbett CE,et al.Prognostic value of immunohistochemistry in gastric neuroendocrine(carcinoid)tumors.Eur J Gastroenterol Hepatol,2007,19(1):21.
[51]任勇,仲召阳,陈寿松,等.大肠腺瘤及腺癌细胞凋亡与p53和bcl-2的表达.华南国防医学杂志,2005,19(5):11.
[52]赵松,段惠军,齐凤英,等.Bcl-2、p53在皮肤肿瘤中的表达及意义.肿瘤研究与临床,2005,17(3):161.
[53]Zavrides H,Zizi - sermpetzoglou A,Elemenoglou I,et,al.Immunohistochemical express of bcl - 2 in UICC stage Ⅰ and Ⅲ colorectal carcinoma patients:correla- tion with c - erbB - 2,p53,ki - 67,CD44,laminin and collagen Ⅳ in evaluating prognostic singnificance.Pol J Pathl,2006,57(3):149.
[54]宋兰云,王学文,胡晓丽,等.凋亡相关bcl-2基因族在儿童神经母细胞瘤中的表达.Tanjin Med J.2005,33(1):20.
[55]Andreeff M,Jiang S,Zhang X,et al.Expression of Bcl-2-related genes in normal and AML progenitors:changes induced by chemotherapy and retinoic acid.Leukemia 1999,13:1881-1892.
[56]Lu Z,Wu Z,Mo Y.Regulation of Bcl-2 expression by Ubc9.Exp cell Res.2006,312:1865-1875.
[57]Weller M,Malipiero U,Aguzzi A,et al.Protooncogene bcl-2 Gne transfer abrogates Fas/APO-1 antibody-mediated apoptosis of human malignant glioma cells and confers resistance to chemotherapeutic drugs and therapeutic irradiation.J Clin Invest.1995,95:2633-2643
[58]Wei L,Cui L,Snider J,Rivkin M.et al.Transplantation of embryonic stem cells overexpressing Bcl-2 promotes functional recovery after transient cerebral ischemia.Neurobiol Dis.2005,19:183-193
[59]Shman TV,Fedasenka UU,Savitski VP,et al.CD34+ leukemic subpopulation predominantly displays lower spontaneous apoptosis and has higher expression levels of Bcl-2 and MDR1 genes than CD34- cells in childhood AML.Ann Hematol.2008,[ahead of print]
[60]Shman TV,Savitski VP,Fedasenka UU,et al.Apoptosis and proliferation differences between CD34+ and CD34- leukemic subpopulations in childhood acute leukemia.Hematology.2007,[ahead of print]
[61]欧扬,郭秀丽.肿瘤干细胞及其耐药机制.生理科学进展.2007,38(2):115-119.
[62]房佰俊,宋永平,魏旭东,等.慢性粒细胞性白血病干细胞抗伊马替尼机制的初步研究.第一届国际肿瘤干细胞学术会议论文集.杭州,2007,85.
[63]Grinstein E,Wemet P.Cellular signaling in normal and cancerous stem cells.Cell Signal.2007,19(12):2428-2433.
[64]Lessard J,Sauvageau G.Bmi21 determines the proliferative capacity of normal and leukacmic stem cells.Nature,2003,423:255-260.
[65]Cotsarelis,G.& Millar,S.E.Towards a molecular understanding of hair loss and its treatment.Trends Mol.Med.2001,7:293-301.
[66]Burger,H.et al.Imatinib mesylate(STI571)is a substrate for the breast cancer resistance protein(BCRP)/ABCG2 drug pump.Blood.2004,104:2940-2942.
[67]Hofmann,W.K.et al.Presence of the BCR-ABL mutation Glu255Lys prior to STI571(imatinib)treatment in patients with Ph+ acute lymphoblastic leukemia.Blood.2003,102:659-661.
[68]Goldie,J.H.& Coldman,A.J.A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate.Cancer Treat.Rep.1979,63:1727-1733.
[69]Bakker,M.et al.99mTc-Sestamibi scanning with SDZ PSC833 as a functional detection method for resistance modulation in patients with solid tumours.AntiCancer Res.1999,19:2349-2353.
[70]Bates,S.E.et al.A phase Ⅰ/Ⅱ study of infusional vinblastine with the P-glyco-protein antagonist valspodar(PSC 833)renal cell carcinoma.Clin.Cancer Res.2004,10:4724-4733.
[71]Allen,J.D.et al.Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C.Mol.Cancer Ther.2002,1:417-425.
[72] Varnum-Finney B, Xu L, Brashem-Stein C, et al. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat. Med,2000,6: 1278-1281
[73] Lee HY, Kleber M, Hari L, et al.Instructive role of Wnt/beta-catenin in sensory fate specification in neural crest stem cells. Science ,2004,303: 1020-1023
[74] Bhardwaj G, Murdoch B, Wu D, et al.Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation. Nat. Immunol,2001,2:172-180
[75] Yilmaz OH, Valdez R, Theisen BK, et al. Pten dependence distinguishes hematopoietic stem cells from leukaemia-initiating cells. Nature , 2006, 441 (25):475-482.
[76] Ohno R, Asou N, Ohnishi K. Treatment of acute promyelocytic leukemia: strategy toward further increase of cure rate. Leukemia,2003,17:1454-1463.
[77] Aguado T, Carracedo A, Julien B, et al. Cannabinoids induceglioma stem-like cell differentiation and inhibitgliomagenesis. J Biol Chem, 2007, 2: [ahead of print].
[78] Feuring BM, Frankel A, Gerhard B, et al. Variable cytotoxicity of diphtheria toxin 388 granulocyte macro2phage colony stimulating factor fusion protein for acute myelogenous leukemia stem cells. Exp Hematol, 2000, 28:1390-1400.
[79] Altundag K, Altundag O, Elkiran ET, et al. Addition of granulocytecolony stimulating factor ( G-CSF) to adjuvant treatment may increase survival in patients with operable breast cancer cells: interaction of G-CSF with dormant micrometastatic breast cancer cells. Med Hypotheses, 2004,63:56-58.
[80] Schatzlein AG. Delivering cancer stem cell therapies-A rolefor nanomedicines. Euro J Cancer, 2006,42:1309-1315.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |