苦参提取物对人乳腺癌MCF-7细胞系肿瘤干细胞样细胞生物学行为的干预研究
|
摘要
最新研究发现,肿瘤干细胞的存在是肿瘤复发和转移的主要原因,它们在常规治疗后残存下来成为肿瘤复发和转移的种子细胞。怎样靶向调控肿瘤干细胞从而提高恶性肿瘤的治愈率是当前亟待研究的课题。长期的临床实践证明,中医中药在预防肿瘤复发专一方面有着独特的优势和特色。但是中医药预防肿瘤复发转移的具体机制至今尚不明了。所以本研究首次将肿瘤干细胞研究与中医药防治肿瘤研究结合在一起,旨在探索中医药是否能以肿瘤干细胞为靶点,通过控制肿瘤干细胞的生物学行为发挥其预防肿瘤复发转移的生物学效应。
本研究根据肿瘤干细胞高表达ABCG2受体从而能外排核染料Hochest33342的特性来进行人乳腺癌细胞MCF-7细胞系肿瘤干细胞的分离纯化,以研究该细胞系肿瘤干细胞的体外增殖能力、再分化能力及与干细胞自我更新密切相关的Wnt信号转导通路中的信号物质的表达等相关生物学行为。
由于中药苦参的有效成分氧化苦参碱(OM,OM)有抑制肿瘤的增殖和转移,诱导肿瘤细胞分化、促进肿瘤细胞凋亡等作用。所以在对肿瘤干细胞的生物学行为进行研究的基础上,本研究又进行了中药单体氧化苦参碱对MCF-7肿瘤干细胞生物学行为的干预作用的研究,以揭示氧化苦参碱对于实体肿瘤干细胞是否存在调控作用,并进一步揭示其干预调控作用是否与Wnt通路的活性有关,并进一步就其干预Wnt信号转导通路的分子水平作用机制进行研究,为该药特异性靶向调控肿瘤干细胞提供实验依据。
1 MCF-7肿瘤干细胞的分离与生物学行为研究
1.1方法
取对数生长期MCF-7细胞消化为细胞悬液,分为两组,一组加入Hoechst33342至终浓度为5μg/ml,另一组同时加入维拉帕米至终浓度100uM,37℃水浴90min,加入PI至终浓度1μg/ml,流式细胞仪分析SP(side population,侧群细胞,肿瘤干细胞样细胞)亚群细胞含量,并据此进行SP亚群的分选培养,以研究SP亚群细胞的增殖能力,集落形成能力,再分化能力等细胞水平的生物学特点。并用Western-Blot,免疫荧光法检测细胞内总β-catenin的表达,流式细胞仪检测磷酸化β-catenin的表达水平,荧光定量PCR检测β-catenin、c-myc、cyclin D1等Wnt通路有关信号物质的mRNA水平等等。以明确肿瘤干细胞的Wnt信号转导通路的特征性表现。
1.2结果
MCF-7细胞系中SP细胞所占比例为4.02±0.18%;SP、non-SP(non-sidepopulation,非侧群细胞,非肿瘤干细胞样细胞)细胞的再培养提示在开始的两天二者增殖速度未见明显差异,而第3、4天SP细胞的增殖速度明显快于non-SP细胞,二者相比有显著性差异;集落形成能力提示,SP细胞的集落形成为30.67±2.57%,而non-SP细胞的集落形成能力13.33±1.76%,二者相比有显著性差异;在Wnt通路关键蛋白质β-catenin的表达方面,SP细胞中总β-catenin的表达显著高于non-SP细胞,而磷酸化β-catenin表达下调;与non-SP细胞相比,该通路的下游信号物质c-myc、cyclin D1的表达在SP细胞中亦呈上调。差异均有统计学意义。
1.3结论
MCF-7细胞系中包含SP亚群;SP细胞经培养后可继续分化成SP和non-SP细胞,说明其具有多向分化潜能;与non-SP细胞相比,具有更高的增殖能力,更强的自我更新能力;说明该细胞系的SP亚群可以代表该细胞系的肿瘤干细胞。而且Wnt通路在该细胞SP亚群细胞中呈活化状态,从另一个侧面说明该通路在肿瘤干细胞的自我更新等其它生物学行为的调控中起重要作用。
2氧化苦参碱对MCF-7细胞生物学行为的调控作用
2.1方法
MTT法检测氧化苦参碱对MCF-7细胞系增殖能力的体外干预作用;AV-PI法进行氧化苦参碱诱导MCF-7细胞凋亡作用的研究;同时以在乳腺癌治疗中常用的DDP为对照,研究了氧化苦参碱对Wnt通路中的信号物质β-catenin,c-myc及cyclinD1的表达的干预作用。
2.2结果
氧化苦参碱在50ug/ml以上对MCF-7细胞的增殖有抑制作用,呈剂量及时间依赖性;该药能诱导MCF-7细胞的凋亡,表现为核染色质浓缩,核固缩及凋亡小体的生成等等;但这些作用均较DDP弱,然而与DDP相比,氧化苦参碱能明显下调Wnt通路的活性,如减少细胞内总β-catenin的表达,增加磷酸化β-catenin的表达,下调c-myc及cyclinD1的表达等等。
2.3结论
氧化苦参碱可以在体外抑制MCF-7细胞的增殖,诱导其凋亡,并能抑制Wnt通路的活性,这有可能是氧化苦参碱抑制MCF-7细胞增殖的原因。
3氧化苦参碱对MCF-7细胞系肿瘤干细胞生物学行为的调控作用
3.1方法
分选得到SP细胞和non-SP细胞进行再培养,分别用MTT法研究氧化苦参碱对这两种不同细胞亚群增殖能力的体外干预作用;流式细胞法检测该药对MCF-7细胞系中SP细胞(干细胞池)数量的干预作用;软琼脂集落形成试验研究氧化苦参碱对不同细胞亚群的自我更新的干预作用;同时以DDP为对照,研究了氧化苦参碱对不同细胞亚群中Wnt通路中的信号物质β-catenin,c-myc及cyclinD1的表达的干预作用。
3.2结果
氧化苦参碱,DDP对不同的细胞亚群的生长均有抑制作用,然而与DDP比较,氧化苦参碱对SP细胞的抑制作用更强(P<0.01),对non-SP的抑制作用弱于DDP;在对SP细胞百分比(干细胞池)的影响方面,氧化苦参碱能明显减少MCF-7细胞系中SP细胞的含量,抑制率达到90%;与DDP相比,氧化苦参碱能明显干预SP细胞的克隆形成,减少细胞内总β-catenin的表达,增加磷酸化β-catenin的表达,下调c-myc及cyclinD1的表达等。
3.3结论
氧化苦参碱可以特异性地、剂量依赖地在体外抑制MCF-7细胞系中肿瘤干细胞样细胞(SP细胞)的增殖,减少SP细胞百分比,降低其自我更新能力,并能下调与肿瘤干细胞生物学行为密切相关的Wnt通路的活性,这提示氧化苦参碱有可能成为清除肿瘤干细胞的靶向药物。
The cancer stem ceils(CSCs) play a critical role in both cancer initiation and relapse as they are resistant to most of cytotoxic agents and able to proliferate indefinitely.The plant alkaloid oxymatrine(OM) has many biological activities including the ability to induce cell cycle arrest and apoptosis,which makes it a potentially useful agent for targeting cancer cells.So in order to determine whether it has beneficial pharmacological properties to eradicate CSCs,we have analyzed the effects of OM on MCF-7 breast cancer cells.Cytotoxicity and cancer stem-like cells (side population,SP) identification and sorting were performed.Inhibitory effect was evaluated on the sorted SP and non-SP cells.SP cells were identified with percentage (4.02±0.18%) in MCF-7 cells.OM caused a dose-dependent reduction in the proliferation of MCF-7 cells and a decrease in SP cells relative to untreated controls. As conon-SPared to non-SP cells,inhibitory effect in the SP cells was higher.
Wnt/β-catenin signaling pathway was also examined by analyzing the expression of total P-catenin and phosphorylated p-catenin in cytoplasm,OM treatment was associated with an inhibition of Wnt/p-catenin signaling pathway relative to untreated controls.These results indicate that the growth inhibitory effects of OM treatment on MCF-7 cells may be partly via effects on SP and Wnt/p-catenin signaling pathway. Further work is warranted to explore whether OM may be a useful novel therapeutic drug for targeting breast CSCs.
1.Isolating and characterizing SP cells from MCF-7 cells
1.1 METHODS:Cells were trpsinized and re-suspended at 10~6cells/ml in conon-SPlete RPMI1640.Hoechst33342 was added to a final concentration of 5μg/ml with or without 100uM verapamil hydrochloride and cells were incubated for 90 minutes in a 37℃water bath.The MCF-7 and the SP/non-SP cells from MCF-7 cultured 7 days were analyzed and sorted by FACS.β-catenin,phosphorylatedp-catenin,c-myc and cyclinDl were also detected by fluorescence,FACS,Western blot and anon-SPlisensor quantitative PCR among SP and non-SP,MCF-7 cells.
1.2 RESULTS:SP is contained in MCF-7 for about 4.02±0.18%.The SP cells perform a higher speed proliferation rate and higher clone formation rate than non-SP cells,and SP cells can be separated into SP and non-SP cells after being cultured 7 days.There is no difference between the percentages of SP in the parental cells and the descendant cells.As we speculated,the expressions of p-catenin,c-myc and cyclinD1 were higher,and phosphorylated p-catenin was lower,as compared with non-SP cells.
1.3 CONCLUSION:The percentage of SP in MCF-7 cells is 4.01±0.18%.The ability of SP cells developing into SP and non-SP means that SP is in the higher hierarchy.And the activity of Wnt signaling pathway is over-regulated in SP cells.
2.The effects of OM on MCF-7 cells
2.1 METHODS:MTT experiments were performed to determine whether OM can inhibit the viability of MCF-7 cells.In order to determine whether OM can induce the apoptosis of MCF-7 cells,the cells treated with different concentrations OM for 48h were stained with AV-PI,and analyzed by FACS,at the same time,the fluorescence microscope detection were performed,β-catenin,phosphorylated p-catenin,c-myc and cyclinD1 were also detected by fluorescence microscope,FACS,Western blot and anon-SPlisensor quantitative PCR among OM treated MCF-7 and the control one. Cisplatin was the positive control drug of these experiments.
2.2 RESULTS:There was a dose and time depended anti-proliferative activity of OM ranging from 62.5ug/ml to 4mg /ml(Fig.4A) and 0.5mg/ml from 6 to 48h.The percentages of Phosphorylatedβ-catenin positive cells by FACS.The percentages were 26.26%,41.50%,and 62.77%in 0.25mg/ml,0.5 mg/ml and 1mg/ml OM treated cells and 18.52%of untreated cells,respectively.The expressions ofβ-catenin,c-myc and cyclinD1 were all decreased in the OM treated cells,as compared with untreated cells.
2.3 CONCLUSION:OM could decrease MCF-7 cell viability,induce MCF-7 cells apoptosis,decrease the expression of totalβ-catenin and its nuclear location,decrease the mRNA of P-catenin,c-myc and cyclinD1 and increase the phosphorylatedβ-catenin in cytoplasm.Most of these effects were mediated in a dose-dependent manner.
3 The effects of OM on cancer stem like cells(SP cells) from MCF-7 cells
3.1 METHODS:MTT experiments were performed to determine whether OM can inhibit the viability of SP cells from MCF-7cells.In order to determine whether OM can decrease the percentage of SP cells in the total of MCF-7 cells,the cells treated with different concentrations OM for 48h were restained with Hochest33342 and analysis by FACS.At the same time,β-catenin,phosphorylatedβ-catenin,c-myc and cyclinD1 were also detected by fluorescence microscope,FACS,Western blot and anon-SPlisensor quantitative PCR among OM treated MCF-7 and the control one. Cisplatin was the positive control drug of these experiments.
3.2 RESULTS:The inhibitory effects of OM on SP cells from MCF-7 cells were significant difference among different concentrations of OM.Conon-SPared with cisplatin,OM showed a higher inhibitory effect in breast CSCs(SP),and a lower inhibitory effect in breast cancer cells(non-SP).In OM-treated cells,the SP population was 3.1%,1.7%,and 0.2%,at 0.25mg/ ml,0.5mg/ml,1mg/ml OM, respectively.The staining intensity of cytoplasm and nuclearβ-catenin of the re-cultured SP cells treated with OM was significiantly decreased,andβ-catenin was typically found at the cell membrane only conon-SPared with controls.The expression of phosphorylatedβ-catenin of re-cultured SP cell treated with OM positive cells were increased and the expression of c-myc and cyclinD1 were all decreased,as compared with untreated cells,but this effect was not observed in cisplatin treated group.
3.3 CONCLUSION:This result showed that the breast cancer stem-like cells(SP) were more sensitive to OM than cisplatin,it leads to a dramatic decrease in the SP population and down regulating the activity of Wnt/β-catenin signaling pathway
本研究根据肿瘤干细胞高表达ABCG2受体从而能外排核染料Hochest33342的特性来进行人乳腺癌细胞MCF-7细胞系肿瘤干细胞的分离纯化,以研究该细胞系肿瘤干细胞的体外增殖能力、再分化能力及与干细胞自我更新密切相关的Wnt信号转导通路中的信号物质的表达等相关生物学行为。
由于中药苦参的有效成分氧化苦参碱(OM,OM)有抑制肿瘤的增殖和转移,诱导肿瘤细胞分化、促进肿瘤细胞凋亡等作用。所以在对肿瘤干细胞的生物学行为进行研究的基础上,本研究又进行了中药单体氧化苦参碱对MCF-7肿瘤干细胞生物学行为的干预作用的研究,以揭示氧化苦参碱对于实体肿瘤干细胞是否存在调控作用,并进一步揭示其干预调控作用是否与Wnt通路的活性有关,并进一步就其干预Wnt信号转导通路的分子水平作用机制进行研究,为该药特异性靶向调控肿瘤干细胞提供实验依据。
1 MCF-7肿瘤干细胞的分离与生物学行为研究
1.1方法
取对数生长期MCF-7细胞消化为细胞悬液,分为两组,一组加入Hoechst33342至终浓度为5μg/ml,另一组同时加入维拉帕米至终浓度100uM,37℃水浴90min,加入PI至终浓度1μg/ml,流式细胞仪分析SP(side population,侧群细胞,肿瘤干细胞样细胞)亚群细胞含量,并据此进行SP亚群的分选培养,以研究SP亚群细胞的增殖能力,集落形成能力,再分化能力等细胞水平的生物学特点。并用Western-Blot,免疫荧光法检测细胞内总β-catenin的表达,流式细胞仪检测磷酸化β-catenin的表达水平,荧光定量PCR检测β-catenin、c-myc、cyclin D1等Wnt通路有关信号物质的mRNA水平等等。以明确肿瘤干细胞的Wnt信号转导通路的特征性表现。
1.2结果
MCF-7细胞系中SP细胞所占比例为4.02±0.18%;SP、non-SP(non-sidepopulation,非侧群细胞,非肿瘤干细胞样细胞)细胞的再培养提示在开始的两天二者增殖速度未见明显差异,而第3、4天SP细胞的增殖速度明显快于non-SP细胞,二者相比有显著性差异;集落形成能力提示,SP细胞的集落形成为30.67±2.57%,而non-SP细胞的集落形成能力13.33±1.76%,二者相比有显著性差异;在Wnt通路关键蛋白质β-catenin的表达方面,SP细胞中总β-catenin的表达显著高于non-SP细胞,而磷酸化β-catenin表达下调;与non-SP细胞相比,该通路的下游信号物质c-myc、cyclin D1的表达在SP细胞中亦呈上调。差异均有统计学意义。
1.3结论
MCF-7细胞系中包含SP亚群;SP细胞经培养后可继续分化成SP和non-SP细胞,说明其具有多向分化潜能;与non-SP细胞相比,具有更高的增殖能力,更强的自我更新能力;说明该细胞系的SP亚群可以代表该细胞系的肿瘤干细胞。而且Wnt通路在该细胞SP亚群细胞中呈活化状态,从另一个侧面说明该通路在肿瘤干细胞的自我更新等其它生物学行为的调控中起重要作用。
2氧化苦参碱对MCF-7细胞生物学行为的调控作用
2.1方法
MTT法检测氧化苦参碱对MCF-7细胞系增殖能力的体外干预作用;AV-PI法进行氧化苦参碱诱导MCF-7细胞凋亡作用的研究;同时以在乳腺癌治疗中常用的DDP为对照,研究了氧化苦参碱对Wnt通路中的信号物质β-catenin,c-myc及cyclinD1的表达的干预作用。
2.2结果
氧化苦参碱在50ug/ml以上对MCF-7细胞的增殖有抑制作用,呈剂量及时间依赖性;该药能诱导MCF-7细胞的凋亡,表现为核染色质浓缩,核固缩及凋亡小体的生成等等;但这些作用均较DDP弱,然而与DDP相比,氧化苦参碱能明显下调Wnt通路的活性,如减少细胞内总β-catenin的表达,增加磷酸化β-catenin的表达,下调c-myc及cyclinD1的表达等等。
2.3结论
氧化苦参碱可以在体外抑制MCF-7细胞的增殖,诱导其凋亡,并能抑制Wnt通路的活性,这有可能是氧化苦参碱抑制MCF-7细胞增殖的原因。
3氧化苦参碱对MCF-7细胞系肿瘤干细胞生物学行为的调控作用
3.1方法
分选得到SP细胞和non-SP细胞进行再培养,分别用MTT法研究氧化苦参碱对这两种不同细胞亚群增殖能力的体外干预作用;流式细胞法检测该药对MCF-7细胞系中SP细胞(干细胞池)数量的干预作用;软琼脂集落形成试验研究氧化苦参碱对不同细胞亚群的自我更新的干预作用;同时以DDP为对照,研究了氧化苦参碱对不同细胞亚群中Wnt通路中的信号物质β-catenin,c-myc及cyclinD1的表达的干预作用。
3.2结果
氧化苦参碱,DDP对不同的细胞亚群的生长均有抑制作用,然而与DDP比较,氧化苦参碱对SP细胞的抑制作用更强(P<0.01),对non-SP的抑制作用弱于DDP;在对SP细胞百分比(干细胞池)的影响方面,氧化苦参碱能明显减少MCF-7细胞系中SP细胞的含量,抑制率达到90%;与DDP相比,氧化苦参碱能明显干预SP细胞的克隆形成,减少细胞内总β-catenin的表达,增加磷酸化β-catenin的表达,下调c-myc及cyclinD1的表达等。
3.3结论
氧化苦参碱可以特异性地、剂量依赖地在体外抑制MCF-7细胞系中肿瘤干细胞样细胞(SP细胞)的增殖,减少SP细胞百分比,降低其自我更新能力,并能下调与肿瘤干细胞生物学行为密切相关的Wnt通路的活性,这提示氧化苦参碱有可能成为清除肿瘤干细胞的靶向药物。
The cancer stem ceils(CSCs) play a critical role in both cancer initiation and relapse as they are resistant to most of cytotoxic agents and able to proliferate indefinitely.The plant alkaloid oxymatrine(OM) has many biological activities including the ability to induce cell cycle arrest and apoptosis,which makes it a potentially useful agent for targeting cancer cells.So in order to determine whether it has beneficial pharmacological properties to eradicate CSCs,we have analyzed the effects of OM on MCF-7 breast cancer cells.Cytotoxicity and cancer stem-like cells (side population,SP) identification and sorting were performed.Inhibitory effect was evaluated on the sorted SP and non-SP cells.SP cells were identified with percentage (4.02±0.18%) in MCF-7 cells.OM caused a dose-dependent reduction in the proliferation of MCF-7 cells and a decrease in SP cells relative to untreated controls. As conon-SPared to non-SP cells,inhibitory effect in the SP cells was higher.
Wnt/β-catenin signaling pathway was also examined by analyzing the expression of total P-catenin and phosphorylated p-catenin in cytoplasm,OM treatment was associated with an inhibition of Wnt/p-catenin signaling pathway relative to untreated controls.These results indicate that the growth inhibitory effects of OM treatment on MCF-7 cells may be partly via effects on SP and Wnt/p-catenin signaling pathway. Further work is warranted to explore whether OM may be a useful novel therapeutic drug for targeting breast CSCs.
1.Isolating and characterizing SP cells from MCF-7 cells
1.1 METHODS:Cells were trpsinized and re-suspended at 10~6cells/ml in conon-SPlete RPMI1640.Hoechst33342 was added to a final concentration of 5μg/ml with or without 100uM verapamil hydrochloride and cells were incubated for 90 minutes in a 37℃water bath.The MCF-7 and the SP/non-SP cells from MCF-7 cultured 7 days were analyzed and sorted by FACS.β-catenin,phosphorylatedp-catenin,c-myc and cyclinDl were also detected by fluorescence,FACS,Western blot and anon-SPlisensor quantitative PCR among SP and non-SP,MCF-7 cells.
1.2 RESULTS:SP is contained in MCF-7 for about 4.02±0.18%.The SP cells perform a higher speed proliferation rate and higher clone formation rate than non-SP cells,and SP cells can be separated into SP and non-SP cells after being cultured 7 days.There is no difference between the percentages of SP in the parental cells and the descendant cells.As we speculated,the expressions of p-catenin,c-myc and cyclinD1 were higher,and phosphorylated p-catenin was lower,as compared with non-SP cells.
1.3 CONCLUSION:The percentage of SP in MCF-7 cells is 4.01±0.18%.The ability of SP cells developing into SP and non-SP means that SP is in the higher hierarchy.And the activity of Wnt signaling pathway is over-regulated in SP cells.
2.The effects of OM on MCF-7 cells
2.1 METHODS:MTT experiments were performed to determine whether OM can inhibit the viability of MCF-7 cells.In order to determine whether OM can induce the apoptosis of MCF-7 cells,the cells treated with different concentrations OM for 48h were stained with AV-PI,and analyzed by FACS,at the same time,the fluorescence microscope detection were performed,β-catenin,phosphorylated p-catenin,c-myc and cyclinD1 were also detected by fluorescence microscope,FACS,Western blot and anon-SPlisensor quantitative PCR among OM treated MCF-7 and the control one. Cisplatin was the positive control drug of these experiments.
2.2 RESULTS:There was a dose and time depended anti-proliferative activity of OM ranging from 62.5ug/ml to 4mg /ml(Fig.4A) and 0.5mg/ml from 6 to 48h.The percentages of Phosphorylatedβ-catenin positive cells by FACS.The percentages were 26.26%,41.50%,and 62.77%in 0.25mg/ml,0.5 mg/ml and 1mg/ml OM treated cells and 18.52%of untreated cells,respectively.The expressions ofβ-catenin,c-myc and cyclinD1 were all decreased in the OM treated cells,as compared with untreated cells.
2.3 CONCLUSION:OM could decrease MCF-7 cell viability,induce MCF-7 cells apoptosis,decrease the expression of totalβ-catenin and its nuclear location,decrease the mRNA of P-catenin,c-myc and cyclinD1 and increase the phosphorylatedβ-catenin in cytoplasm.Most of these effects were mediated in a dose-dependent manner.
3 The effects of OM on cancer stem like cells(SP cells) from MCF-7 cells
3.1 METHODS:MTT experiments were performed to determine whether OM can inhibit the viability of SP cells from MCF-7cells.In order to determine whether OM can decrease the percentage of SP cells in the total of MCF-7 cells,the cells treated with different concentrations OM for 48h were restained with Hochest33342 and analysis by FACS.At the same time,β-catenin,phosphorylatedβ-catenin,c-myc and cyclinD1 were also detected by fluorescence microscope,FACS,Western blot and anon-SPlisensor quantitative PCR among OM treated MCF-7 and the control one. Cisplatin was the positive control drug of these experiments.
3.2 RESULTS:The inhibitory effects of OM on SP cells from MCF-7 cells were significant difference among different concentrations of OM.Conon-SPared with cisplatin,OM showed a higher inhibitory effect in breast CSCs(SP),and a lower inhibitory effect in breast cancer cells(non-SP).In OM-treated cells,the SP population was 3.1%,1.7%,and 0.2%,at 0.25mg/ ml,0.5mg/ml,1mg/ml OM, respectively.The staining intensity of cytoplasm and nuclearβ-catenin of the re-cultured SP cells treated with OM was significiantly decreased,andβ-catenin was typically found at the cell membrane only conon-SPared with controls.The expression of phosphorylatedβ-catenin of re-cultured SP cell treated with OM positive cells were increased and the expression of c-myc and cyclinD1 were all decreased,as compared with untreated cells,but this effect was not observed in cisplatin treated group.
3.3 CONCLUSION:This result showed that the breast cancer stem-like cells(SP) were more sensitive to OM than cisplatin,it leads to a dramatic decrease in the SP population and down regulating the activity of Wnt/β-catenin signaling pathway
引文
1 J.C,Congenitales,Nirerenq Md:Virchows Arch 1875;65:6.
2 Lapidot T,Sirard C,Vormoor J,al.e:A cell initiating human acute myeloid leukaemia after transplantation into scid mice.Nature 1994;367:4.
3 Reya T,Duncan AW,Ailles L,Domen J,Scherer DC,Willert K,Hintz L,Nusse R,Weissman IL:A role for wnt signalling in self-renewal of haematopoietic stem cells.Nature 2003;423:409-414.
4 Singh SK,Clarke ID,Hide T,Dirks PB:Cancer stem cells in nervous system tumors.Oncogene 2004;23:7267-7273.
5 Ponti D,Costa A,Zaffaroni N,Pratesi G,Petrangolini G,Coradini D,Pilotti S,Pierotti MA,Daidone MG:Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties.Cancer Res 2005;65:5506-5511.
6 Al-Hajj M,Wicha MS,Benito-Hernandez A,Morrison SJ,Clarke MF:Prospective identification of tumorigenic breast cancer cells.Proc Natl Acad Sci U S A 2003;100:3983-3988.
7 Taylor MD,Liu L,Raffel C,Hui CC,Mainprize TG,Zhang X,Agatep R,Chiappa S,Gao L,Lowrance A,Hao A,Goldstein AM,Stavrou T,Scherer SW,Dura WT,Wainwright B,Squire JA,Rutka JT.Hogg D:Mutations in sufu predispose to medulloblastoma.Nat Genet 2002;31:306-310.
8 Perez-Losada J,Balmain A:Stem-cell hierarchy in skin cancer.Nat Rev Cancer 2003:3:434-443.
9 Richardson GD,Robson CN,Lang SH,Neal DE,Maitland NJ,Collins AT:Cd 133,a novel marker for human prostatic epithelial stem cells.J Cell Sci 2004;117:3539-3545.
10 Collins AT,Berry PA,Hyde C,Stower MJ,Maitland NJ:Prospective identification of tumorigenic prostate cancer stem cells.Cancer Res 2005;65:10946-10951.
11 Seigel GM,Canon-SPbell LM,Narayan M,Gonzalez-Fernandez F:Cancer stem cell characteristics in retinoblastoma.Mol Vis 2005;11:729-737.
12 Li C,Heidt DG,Dalerba P.Burant CF,Zhang L,Adsay V:Wicha M,Clarke MF,Simeone DM:Identification of pancreatic cancer stem cells.Cancer Res 2007;67:l030-1037.
13 Fiegel HC,Gluer S,Roth B,Rischewski J,von Schweinitz D,Ure B,Lambrecht W.Kluth D:Stem-like cells in human hepatoblastoma.J Histochem Cytochem 2004;52:1495-1501.
14 Houghton J,Stoicov C.,Nomura S,Rogers AB,Carlson J,Li H,Cai X,Fox JG,Goldenring JR,Wang TC:Gastric cancer originating from bone marrow-derived cells.Science 2004;306:1568-1571.
15 Kim CF,Jackson EL,Woolfenden AE,Lawrence S,Babar I,Vogel S,Crowley D,Bronson RT,Jacks T:Identification of bronchioalveolar stem cells in normal lung and lung cancer.Cell 2005;121:823-835.
16 Setoguchi T,Taga T,Kondo T:Cancer stem cells persist in many cancer cell lines.Cell Cycle 2004;3:414-415.
17 Patrawala L,Calhoun T,Schneider-Broussard R,Zhou J,Claypool K,Tang DG:Side,population is enriched in tumorigenic,stem-like cancer cells,whereas abcg2+ and abcg2-cancer cells are similarly tumorigenic.Cancer Res 2005;65:6207-6219.
18 Kondo T,Setoguchi T,Taga T:Persistence of a small subpopulation of cancer stem-like cells in the c6 glioma cell line.Proc Natl Acad Sci U S A 2004;101:781-786.
19 Kucia M,Reca R,Miekus K,Wanzeck J,Wojakowski W,Janowska-Wieczorek A,Ratajczak J,Ratajczak MZ:Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms:Pivotal role of the sdf-l-cxcr4 axis.Stem Cells 2005;23:879-894.
20 Li L,Neaves WB:Normal stem cells and cancer stem cells:The niche matters.Cancer Res 2006;66:4553-4557.
21 Singh SK,Hawkins C.,Clarke ID,Squire JA,Bayani J,Hide T,Henkelman RM,Cusimano MD,Dirks PB:Identification of human brain tumour initiating cells.Nature 2004;432:396-401.
22 Leslie EM,Deeley RG,Cole SP:Multidrug resistance proteins:Role of p-glycoprotein,mrpl,mrp2,and bcrp(abcg2)in tissue defense.Toxicol Appl Pharmacol 2005;204:216-237.
23 Zhou S,Morris JJ,Barnes Y,Lan L,Schuetz JD,Sorrentino BP:Bcrpl gene expression is required for normal numbers of side population stem cells in mice,and confers relative protection to mitoxantrone in hematopoietic cells in vivo.Proc Natl Acad Sci U S A 2002;99:12339-12344.
24 Staud F,Pavek P:Breast cancer resistance protein(bcrp/abcg2).Int J Biochem Cell Biol 2005;37:720-725.
25 Dean M,Fojo T,Bates S:Tumour stem cells and drug resistance.Nat Rev Cancer 2005;5:275-284.
26 Polyak K,Hahn WC:Roots and stems:Stem cells in cancer.Nat Med 2006;! 2:296-300.
27 Kai T,Spradling A:Differentiating germ cells can revert into functional stem cells in drosophila melanogaster ovaries.Nature 2004;428:564-569.
28 Tsuji-Takayama K,Inoue T,Ijiri Y,Otani T,Motoda R,Nakamura S,Orita K:Demethylating agent,5-azacytidine,reverses differentiation of embryonic stem cells.Biochem Biophys Res Commun 2004;323:86-90.
29 von Melchner H,Hoffken K:Human placental conditioned medium reverses apparent commitment to differentiation of human promyelocytic leukemia cells(hl60).Blood 1985;66:1469-1472.
30 Pardal R,Clarke MF.Morrison SJ:Applying the principles of stem-cell biology to cancer.Nat Rev Cancer 2003;3:895-902.
31 Huntly BJ,Gilliland DG:Leukaemia stem cells and the evolution of cancer-stem-cell research.Nat Rev Cancer 2005;5:311-321.
32 Yamashita YM,Fuller MT,Jones DL:Signaling in stem cell niches:Lessons from the drosophila germline.J Cell Sci 2005;118:665-672.
33 Moore JC,Sumerel JL,Schnackenberg BJ,Nichols JA,Wikramanayake A,Wessel GM,Marzluff WF:Cyclin d and cdk4 are required for normal development beyond the blastula stage in sea urchin embryos.Mol Cell Biol 2002;22:4863-4875.
34 Niemann C:Controlling the stem cell niche:Right time,right place,right strength.Bioessays 2006;28:1-5.
35 Dontu G,Jackson KW,McNicholas E,Kawamura MJ,Abdallah WM,Wicha MS:Role of notch signaling in cell-fate determination of human mammary stem/progenitor cells.Breast Cancer Res 2004;6:R605-615.
36 Varjosalo M,Li SP,Taipale J:Divergence of hedgehog signal transduction mechanism between drosophila and mammals.Dev Cell 2006;10:177-186.
37 King TJ,DiBerardino MA:Transplantation of nuclei from the frog renal adenocarcinoma.I.Development of tumor nuclear-transplant embryos.Ann N Y Acad Sci 1965;126:115-126.
38 Serov O,Matveeva N,Kuznetsov S,Kaftanovskaya E,Mittmann J:Embryonic hybrid cells:A powerful tool for studying pluripotency and reprogramming of the differentiated cell chromosomes.An Acad Bras Cienc 2001;73:561 -568.
39 Feuring-Buske M,Frankel AE,Alexander RL,Gerhard B,Hogge DE:A diphtheria toxin- interleukin 3 fusion protein is cytotoxic to primitive acute myeloid leukemia progenitors but spares normal progenitors.Cancer Res 2002;62:1730-1736.
40 Jin L,Hope KJ,Zhai Q,Smadja-Joffe F,Dick JE:Targeting of cd44 eradicates human acute myeloid leukemic stem cells.Nat Med 2006;12:1167-1174.
41 Guzman ML,Swiderski CF,Howard DS,Grimes BA,Rossi RM,Szilvassy SJ,Jordan CT:Preferential induction of apoptosis for primary human leukemic stem cells.Proc Natl Acad Sci U S A 2002;99:16220-16225.
42 Recher C.,Beyne-Rauzy O,Demur C.,Chicanne G,Dos Santos C.,Mas VM,Benzaquen D,Laurent G,Huguet F,Payrastre B:Antileukemic activity of rapamycin in acute myeloid leukemia.Blood 2005;105:2527-2534.
43 Xu Q,Thonon-SPson JE,Carroll M:Mtor regulates cell survival after etoposide treatment in primary ami cells.Blood 2005;106:4261-4268.
44 Calabrese C.,Poppleton H,Kocak M,HoggTL,Fuller C.,Hamner B,Oh EY.Gaber MW,Finklestein D,Allen M,Frank A,Bayazitov IT,Zakharenko SS,Gajjar A,Davidoff A,Gilbertson RJ:A perivascular niche for brain tumor stem cells.Cancer Cell 2007:11:69-82.
45 高瑞兰：人参总皂甙对白血病祖细胞作用的实验观察．上海中医药杂志 1999；10：3．
46 Funayama N,Fagotto F,McCrea P,Gumbiner BM:Embryonic axis induction by the amiadiilo repeat domain of beta-catenin:Evidence for intracellular signaling.J Cell Biol 1995;128:959-968.
47 Balic M,Lin H,Young L,Hawes D,Giuliano A,McNamara G,Datar RH,Cote RJ:Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype.Clin Cancer Res 2006;12:5615-5621.
48 Kleber M,Sommer L:Wnt signaling and the regulation of stem cell function.Curr Opin Cell Biol 2004;16:681-687.
49 Kuhnert F,Davis CR,Wang HT,Chu P,Lee M,Yuan J,Nusse R,Kuo CJ:Essential requirement for wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of dickkopf-1.Proc Natl Acad Sci U S A 2004;101:266-271.
50 van Genderen C.,Okamura RM,Farinas I,Quo RG,Parslow TG,Bruhn L,Grosschedl R:Development of several organs that require inductive epithelial-mesenchymal interactions is inon-SPaired in lef-1-deficient mice.Genes Dev 1994;8:2691-2703.
51 Teuliere J,Faraldo MM,Deugnier MA,Shtutman M,Ben-Ze'ev A,Thiery JP,Glukhova MA: Targeted activation of beta-catenin signaling in basal mammary epithelial cells affects mammary development and leads to hyperplasia.Development 2005;132:267-277.
52 Gregorieff A,Clevers H:Wnt signaling in the intestinal epithelium:From endoderm to cancer.Genes Dev 2005;19:877-890.
53 Kinzler KW,VogelsteinB:Life(and death)in a malignant tumour.Nature 1996;379:19-20.
54 Lu D,Zhao Y,Tawatao R,Cottam HB,Sen M,Leoni LM,Kipps TJ,Corr M,Carson DA:Activation of the wnt signaling pathway in chronic lynon-SPhocytic leukemia.Proc Natl Acad Sci USA 2004;101:3118-3123.
55 McWhirter JR,Neuteboom ST,Wancewicz EV,Monia BP.Downing JR,Murre C:Oncogenic homeodomain transcription factor e2a-pbxl activates a novel wnt gene in pre-b acute lynon-SPhoblastoid leukemia.Proc Natl Acad Sci U S A 1999;96:11464-11469.
56 Breuhahn K,Longerich T,Schirmacher P:Dysregulation of growth factor signaling in human hepatocellular carcinoma.Oncogene 2006;25:3787-3800.
57 Jin LH,Shao QJ,Luo W,Ye ZY,Li Q,Lin SC:Detection of point mutations of the axinl gene in colorectal cancers.Int J Cancer 2003:107:696-699.
58 Bafico A,Liu G,Goldin L,Harris V.Aaronson SA:An autocrine mechanism for constitutive wnt pathway activation in human cancer cells.Cancer Cell 2004;6:497-506.
59 Brabletz T,Jung A,Hermann K,Gunther K,Hohenberger W,Kirchner T:Nuclear overexpression of the oncoprotein beta-catenin in colorectal cancer is localized predominantly at the invasion front.Pathol Res Pract 1998;194:701-704.
60 Brabletz T,Jung A,Reu S,Porzner M,Hlubek F,Kunz-Schughart LA,Knuechel R,Kirchner T:Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment.Proc Natl Acad Sci U S A 2001;98:10356-10361.
61 Kirchner T,Brabletz T:Patterning and nuclear beta-catenin expression in the colonic adenoma-carcinoma sequence.Analogies with embryonic gastrulation.Am J Pathol 2000;157:1113-1121.
62 Janssen KP.Alberici P.Fsihi H,Gaspar C.,Breukel C.,Franken P.Rosty C.,Abal M,El Marjou F.Smits R,Louvard D,Fodde R,Robine S:Ape and oncogenic kras are synergistic in enhancing wnt signaling in intestinal tumor formation and progression.Gastroenterology 2006;131:1096-1109.
63 Shulewitz M,Soloviev I,Wu T,Koeppen H,Polakis P,SakanakaC:Repressor roles for tcf-4 and sfrpl in wnt signaling in breast cancer.Oncogene 2006;25:4361-4369.
64 Lin S Y,Xia W,Wang JC.,Kwong KY,Spohn B,Wen Y,Pestell RG,Hung MC:Beta-catenin,a novel prognostic marker for breast cancer:Its roles in cyclin d1 expression and cancer progression.Proc Natl Acad Sci U S A 2000;97:4262-4266.
65 Ormestad M,Astorga J,Landgren H,Wang T,Johansson BR,Miura N,Carlsson P:Foxfl and foxf2 control murine gut development by limiting mesenchymal wnt signaling and promoting extracellular matrix production.Development 2006;133:833-843.
66 Rasola A,Fassetta M,De Bacco F,D'Alessandro L,Gramaglia D,Di Renzo MF,Comoglio PM:A positive feedback loop between hepatocyte growth factor receptor and beta-catenin sustains colorectal cancer cell invasive growth.Oncogene 2007;26:1078-1087.
67 Yang L,Lin C.,Liu ZR:P68 rna helicase mediates pdgf-induced epithelial mesenchymal transition by displacing axin from beta-catenin.Cell 2006;127:139-155.
68 Brown JR,DuBois RN:Cox-2:A molecular target for colorectal cancer prevention.J Clin Oncol 2005;23:2840-2855.
69 Castellone MD,Teramoto H,Williams BO,Druey KM,Gutkind JS:Prostaglandin e2 promotes colon cancer cell growth through a gs-axin-beta-catenin signaling axis.Science 2005;310:1504-1510.
70 Smith K,Bui TD,Poulsom R,Kaklamanis L,Williams G,Harris AL:Up-regulation of macrophage wnt gene expression in adenoma-carcinoma progression of human colorectal cancer.Br J Cancer 1999;81:496-502.
71 Eswarakumar VP,Lax I,Schlessinger J:Cellular signaling by fibroblast growth factor receptors.Cytokine Growth Factor Rev 2005;16:139-149.
72 Katoh M:Fgf signaling network in the gastrointestinal tract(review).Int J Oncol 2006;29:163-168.
73 Katoh M:Epithelial-mesenchymal transition in gastriG cancer(review).Int J Oncol 2005;27:1677-1683.
74 Katoh M:Notch signaling in gastrointestinal tract(review).Int J Oncol 2007;30:247-251.
75 Katoh Y,Katoh M:Hedgehog signaling pathway and gastrointestinal stem cell signaling network(review).Int J Mol Med 2006;18:1019-1023.
76 Katoh Y,Katoh M:Wnt antagonist,sfrpl,is hedgehog signaling target.Int J Mol Med 2006;17:171-175.
77 Katoh M:Networking of wnt,fgf,notch,bnon-SP,and hedgehog signaling pathways during carcinogenesis.Stem Cell Rev 2007;3:30-38.
78 Harris GJ,Senagore AJ,Lavery IC,Church JM,Fazio VW:Factors affecting survival after palliative resection of colorectal carcinoma.Colorectal Dis 2002;4:31-35.
79 Couzin J:Medicine.Tracing the steps of metastasis,cancer's menacing ballet.Science 2003;299:1002-1006.
80 Zhang J,Niu C,Ye L,Huang H,He X,Tong WG,Ross J,Haug J,Johnson T,Feng JQ,Harris S,Wiedemann LM,Mishina Y,Li L:Identification of the haematopoietic stem cell niche and control ofthe niche size.Nature 2003;425:836-841.
81 Lowry WE,Blanpain C,Nowak JA,Guasch G,Lewis I,Fuchs E:Defining the inon-SPact of beta-catenin/tcf transactivation on epithelial stem cells.Genes Dev 2005;19:1596-1611.
82 Heissig B,Hattori K,Dias S,Friedrich M,Ferris B,Hackett NR,Crystal RG,Besmer P,Lyden D,Moore MA,Werb Z,Rafii S:Recruitment of stem and progenitor cells from the bone marrow niche requires mnon-SP-9 mediated release of kit-ligand.Cell 2002;109:625-637.
83 Curran S,Murray GI:Matrix metalloproteinases in tumour invasion and metastasis.J Pathol 1999:189:300-308.
84 Crowe DL,Ohannessian A:Recruitment of focal adhesion kinase and paxillin to betal integrin promotes cancer cell migration via mitogen activated protein kinase activation.BMC Cancer 2004;4:18.
85 Kang H,Watkins G,Douglas-Jones A,Mansel RE,Jiang WG:The elevated level of cxcr4 is correlated with nodal metastasis of human breast cancer.Breast 2005;14:360-367.
86 Venezia TA,Merchant AA,Ramos CA.Whitehouse NL,Young AS,Shaw CA,Goodell MA:Molecular signatures of proliferation and quiescence in hematopoietic stem cells.PLoS Biol 2004;2:e301.
87 Cairns J:The cancer problem.Sci Am 1975;233:64-72,77-68.
88 Wang S,Yang D,Lippman ME:Targeting bcl-2 and bcl-xl with nonpeptidic small-molecule antagonists.Semin Oncol 2003;30:133-142.
89 Graham SM,Jorgensen HG,Allan E,Pearson C,Alcorn MJ,Richmond L,Holyoake TL:Primitive,quiescent,philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to sti571 in vitro.Blood 2002;99:319-325.
90 Paget S:The distribution of secondary growths in cancer of the breast.1889.Cancer Metastasis Rev 1989;8:98-101.
91 Tu SM,Lin SH,Logothetis CJ:Stem-cell origin of metastasis and heterogeneity in solid tumours.Lancet Oncol 2002;3:508-513.
92 Jamieson CH,Ailles LE,Dylla SJ,Muijtjens M,Jones C,Zehnder JL,Gotlib J,Li K,Manz MG,Keating A,Sawyers CL,Weissman IL:Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis cml.N Engl J Med 2004;351:657-667.
93 Korinek V,Barker N,Morin PJ,van Wichen D,de Weger R,Kinzler KW,Vogelstein B,Clevers H:Constitutive transcriptional activation by a beta-catenin-tcf conon-SPlex in ape-/-colon carcinoma.Science 1997;275:1784-1787.
94 Gat U,DasGupta R,Degenstein L,Fuchs E:De novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin.Cell 1998;95:605-614.
95 Ming Kwan K,Li AG,Wang XJ,Wurst W,Behringer RR:Essential roles of bnon-SPr-ia signaling in differentiation and growth of hair follicles and in skin tumorigenesis.Genesis 2004;39:10-25.
96 He XC,Zhang J,Tong WG,Tawfik O,Ross J,Scoville DH,Tian Q,Zeng X,He X,Wiedemann LM,Mishina Y,Li L:Bnon-SP signaling inhibits intestinal stem cell self-renewal through suppression of wnt-beta-catenin signaling.Nat Genet 2004;36:1117-1121.
97 Dubey P,Wu H,Reiter RE,Witte ON:Alternative pathways to prostate carcinoma activate prostate stem cell antigen expression.Cancer Res 2001;61:3256-3261.
98 Gao CL,Dean RC,Pinto A,Mooneyhan R,Connelly RR,McLeod DG,Srivastava S,Moul JW:Detection of circulating prostate specific antigen expressing prostatic cells in the bone marrow of radical prostatectomy patients by sensitive reverse transcriptase polymerase chain reaction.J Urol 1999;161:1070-1076.
99 林洪生,李树奇,朴炳奎:中医复方对肺癌患者抑瘤抗转移作用的研究.中国中西医结合外科杂志1998;4:3.
100 刘嘉湘,施志明,徐振晔:滋阴生津益气升阳法 治疗晚期原发性肺癌的临床研究.中医杂志 1995;36:4.
101 林洪生:中医药防治肿瘤复发与转移的研究概况.医学理论与实践 1999;12:5.
102 林洪生,彩虹,黄启福:金安粉针剂对肺癌细胞系超微结构的影响.中国病理生理杂志2004;20:6.
103 娄金丽,邱全瑛.林洪生:小檗碱对人胃癌细胞增殖、细胞周期及cd44v6 表达的影响.中国免疫学杂志 2004;20:3.
104 张永健:复方中药注射液对人肝癌细胞体外杀伤效应及其对细胞周期的影响.中西医结合杂志1989;9:2.
105 徐建国,任连生,马俊英:302种传统治癌中草药水提液对h1 260细胞的诱导分化及细胞毒作用.山西医学杂志 1991;20:1.
106 司维柯,韩风,秦建华:苦参提取液诱导k562细胞分化的细胞化学观察.中国组织化学与细胞化学杂志,1997;6:1.
107 翁玲,刘学英,刘彦:黄芪多糖对小鼠骨髓及外周血造血干细胞的增殖及动员作用.基础医学与临床2003;23:4.
108 徐传毅,何伟.方斌:生脉成骨方对股骨头坏死i型胶原表达的调节作用研究.现代中西医结合杂志2003;6:3.
109 张艳军,范祥.胡利民:不同治则中药单体对体外培养神经干细胞分化的影响.天津中医药2004;21:2.
110 吴理茂,张荣利,刘红:展望中药在心肌细胞移植中的作用.中国中西医结合杂志2003;23:3.
111 Ricci-Vitiani L,Lombardi DG,Pilozzi E,Biffoni M,Todaro M,Peschle C,De Maria R:Identification and expansion of human colon-cancer-initiating cells.Nature 2007;445:111-115.
112 WuC,Alman BA:Side population cells in human cancers.Cancer Lett 2008;268:1-9.
113 Dontu G,Wicha MS:Survival of mammary stem cells in suspension culture:Incn-SPlications for stem cell biology and neoplasia.J Mammary Gland Biol Neoplasia 2005;10:75-86.
114 Goodell MA,Brose K,Paradis G,Conner AS,Mulligan RC:Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo.J Exp Med 1996:183:1797-1806.
115 Alvi AJ,Clayton H,Joshi C,Enver T,Ashworth A,Vivanco MM,Dale TC,Smalley MJ:Functional and molecular characterisation of mammary side population cells.Breast Cancer Res 2003;5:R1-8.
116 Donnenberg VS,Landreneau RJ,Donnenberg AD:Tumorigenic stem and progenitor cells:Inon-SPlications for the therapeutic index of anti-cancer agents.J Control Release 2007;122:385-391.
117 Hirschmann-Jax C.,Foster AE,Wulf GG,Nuchtern JG,Jax TW,Gobel U,Goodell MA,Brenner MK:A distinct“Side population”Of cells with high drug efflux capacity in human tumor cells.Proc Natl Acad Sci U S A 2004;101:14228-14233.
118 Haraguchi N,UtsunomiyaT,Inoue H,Tanaka F,Mimori K,Barnard GF,Mori M:Characterization of a side population of cancer cells from human gastrointestinal system.Stem Cells 2006;24:506-513.
119 Wang J,Guo LP,Chen LZ,Zeng YX,Lu SH:Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line.Cancer Res 2007;67:3716-3724.
120 Ho MM,Ng AV,Lam S,Hung J Y:Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells.Cancer Res 2007;67:4827-4833.
121 ChibaT.Kita K,Zheng Y W.Yokosuka O,Saisho H,lwama A,Nakauchi H,Taniguchi H:Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties.Hepatology 2006;44:240-251.
122 Szotek PP,Pieretti-Vanmarcke R,Masiakos PT.Dinulescu DM,Connolly D,Foster R,Dombkowski D,Preffer F,Maclaughlin DT,Donahoe PK:Ovarian cancer side population defines cells with stem cell-like characteristics and mullerian inhibiting substance responsiveness.Proc Natl Acad Sci U S A 2006;103:11154-11159.
123 Telford WG,Frolova EG:Discrimination of the hoechst side population in mouse bone marrow with violet and near-ultraviolet laser diodes.Cytometry A 2004;57:45-52.
124 Liu Y,Lu WL,Guo J,Du J,Li T,Wu JW,Wang GL,Wang JC.,Zhang X,Zhang Q:A potential target associated with both cancer and cancer stem cells:A combination therapy for eradication of breast cancer using vinorelbine stealthy liposomes plus parthenolide stealthy liposomes.J Control Release 2008;129:18-25.
125 Farnie G,Clarke RB:Mammary stem cells and breast cancer—role of notch signalling.Stem Cell Rev 2007;3:169-175.
126 Kim M,Turnquist H,Jackson J,Sgagias M,Yan Y,Gong M,Dean M,Sharp JG,Cowan K:The multidrug resistance transporter abcg2(breast cancer resistance protein 1)effluxes hoechst 33342 and is overexpressed in hematopoietic stem cells.Clin Cancer Res 2002;8:22-28.
127 Hu C,Li H,Li J,Zhu Z,Yin S,Hao X,Yao M,Zheng S,Gu J:Analysis of abcg2 expression and side population identifies intrinsic drug efflux in the hcc cell line mhcc-971 and its modulation by akt signaling.Carcinogenesis 2008;29:2289-2297.
128 She JJ,Zhang PG,Wang ZM,Gan WM,Che XM:Identification of side population cells from bladder cancer cells by dyecycle violet staining.Cancer Biol Ther 2008;7:1663-1668.
129 Li Y,Welm B,Podsypanina K,Huang S,Chamorro M,Zhang X,Rowlands T,Egeblad M,Cowin P.Werb Z,Tan LK,Rosen JM,Varmus HE:Evidence that transgenes encoding conon-SPonents of the wnt signaling pathway preferentially induce mammary cancers from progenitor cells.ProcNatl Acad Sci USA2003;100:15853-15858.
130 Liu BY,McDermott SP,Khwaja SS,Alexander CM:The transforming activity of wnt effectors correlates with their ability to induce the accumulation of mammary progenitor cells.Proc Natl Acad Sci USA 2004;101:4158-4163.
131 Shackleton M,Vaillant F.Sinon-SPson KJ,Stingl J,Smyth GK,Asselin-Labat ML,Wu L,Lindeman GJ,Visvader JE:Generation of a functional mammary gland from a single stem cell.Nature 2006;439:84-88.
132 李志琴,章静波:细胞周期调控与肿瘤.癌症进展杂志2004;2:6.
133 Imbert A,Eelkema R,Jordan S,Feiner H,Cowin P:Delta n89 beta-catenin induces precocious development,differentiation,and neoplasia in mammary gland.J Cell Biol 2001;153:555-568.
134 Packham G,Cleveland JL:C-mycand apoptosis.Biochim Biophys Acta 1995;1242:11-28.
135 Hoffman B,Liebermann DA:Apoptotic signaling by c-myc.Oncogene 2008;27:6462-6472.
136 Dang CV:C-myc target genes involved in cell growth,apoptosis,and metabolism.Mol Cell Biol 1999;19:1-11.
137 Dang CV,Resar LM,Emison E,Kim S,Li Q,Prescott JE,Wonsey D,Zeller K:Function of the c-myc oncogenic transcription factor.Exp Cell Res 1999;253:63-77.
138 Elend M,Eilers M:Cell growth:Downstream of myc-to grow or to cycle?Curr Biol 1999;9:R936-938.
139 Prendergast GC:Mechanisms of apoptosis by c-myc.Oncogene 1999;18:2967-2987.
140 Guerin M,Barrois M,Terrier MJ,Spielmann M,Riou G:Overexpression of either c-myc or cerbb-2/neu proto-oncogenes in human breast carcinomas:Correlation with poor prognosis. Oncogene Res 1988;3:21-31.
141 Mariani-Costantini R,Escot C,Theillet C,Gentile A,Merlo G,Lidereau R,Callahan R:In situ c-myc expression and genomic status of the c-myc locus in infiltrating ductal carcinomas of the breast.Cancer Res 1988;48:199-205.
142 Tervahauta AI,Syrjanen SM,Kallio PJ,Syrjanen KJ:Immunohistochemistry,in situ hybridization and polymerase chain reaction(pcr) in detecting c-myc expression in human malignancies.Anticancer Res 1992;12:1005-1011.
143 Sandgren EP,Luetteke NC,Palmiter RD,Brinster RL,Lee DC:Overexpression of tgf alpha in transgenic mice:Induction of epithelial hyperplasia,pancreatic metaplasia,and carcinoma of the breast.Cell 1990;61:1121-1135.
144 Ozaki S,Ikeda S,Ishizaki Y,Kurihara T,Tokumoto N,Iseki M,Arihiro K,Kataoka T,Okajima M,Asahara T:Alterations and correlations of the conon-SPonents in the wnt signaling pathway and its target genes in breast cancer.Oncol Rep 2005;14:1437-1443.
145 Cowling VH,D'Cruz CM,Chodosh LA,Cole MD:C-myc transforms human mammary epithelial cells through repression of the wnt inhibitors dkkl and sfrpl.Mol Cell Biol 2007;27:5135-5146.
146 陶上乘,王静珍:苦豆子生物碱的药理作用.中国药学杂志 1992;27:4.
147 李先荣,刘德宽:苦参生物碱抗小鼠移植性肿瘤研究.中西医结合杂志1982;2:1.
148 王秀坤,李家实:白刺花生物碱的体外抑瘤作用.北京中医药大学学报1996;19:2.
149 张燕军,夏天,赵建斌.:苦参碱对smmc-7721细胞系的诱导分化作用.第四军医大学学报1998;19:4.
150 程光,章翔,费舟:苦参碱对bt325胶质瘤细胞的增殖抑制和诱导凋亡作用.第四军医大学学报;23:3.
151 张百红,岳红云,李新民:苦参碱抗癌作用与诱导肿瘤细胞凋亡.肿瘤研究与临床1999;12:2.
152 Lindenboim L,Diamond R,Rothenberg E,Stein R:Apoptosis induced by serum deprivation of pc 12 cells is not preceded by growth arrest and can occur at each phase of the cell cycle.Cancer Res 1995;55:1242-1247.
153 李龙江,陈志琼.郑元义:氧化苦参碱对人卵巢癌细胞skov-3体外活性的影响.重庆医科大学学报2003;17:2.
154 侯华新,黎丹戎,栾英姿:氧化苦参碱诱导卵巢癌skov-3细胞凋亡作用的实验研究[中国药理学通报2002;18:4.
155 王兵,王国俊,徐均:氧化苦参碱对肿瘤诱导血管内皮细胞增殖的抑制作用.实用肿瘤杂志 2000;15:4.
156 许相儒,蒋纪恺:苦参及其生物碱抗肿瘤活性研究进展.中国中西医结合杂志199818:3.
157 田涛,吴朝晖,金惠铭:原位末端标记(tunel)法、流式细胞仪pi法和pi,annexin v双标记法检测细胞凋亡的比较.中国微循环1999;3:5.
158 司徒镇强,吴军正(eds):细胞培养.ed.西安,世界图书出版社,1996,vol第一版,pp 135.
159 Jin Y,Hu J,Wang Q,Li Z,Chen Y:Effects of OM on the apoptosis of human esophageal carcinoma eca109 cell line and its mechanism.J Huazhong Univ Sci Technolog Med Sci 2008:28:314-316.
160 Song MQ,Zhu JS,Chen JL,Wang L,Da W,Zhu L,Zhang WP:Synergistic effect of OM and angiogenesis inhibitor nm-3 on modulating apoptosis in human gastric cancer cells.World J Gastroenterol 2007;13:1788-1793.
161 Song G,Luo Q,Qin J,Wang L,Shi Y,Sun C:Effects of OM on proliferation and apoptosis in human hepatoma cells.Colloids Surf B Biointerfaces 2006;48:1-5.
162 Wieczorek M,Paczkowska A,Guzenda P.Majorek M,Bednarek AK,Lanon-SParska-Przybysz M:Silencing of wnt-1 by sirna induces apoptosis of mcf-7 human breast cancer cells.Cancer Biol Ther 2008;7:268-274.
163 Huang WS,Wang JP,Wang T,Fang JY,Lan P,Ma JP:Shma-mediated gene silencing of betacatenin inhibits growth of human colon cancer cells.World J Gastroenterol 2007;13:6581-6587.
164 Torres VA,Tapia JC,Rodriguez DA,Lladser A,Arredondo C,Leyton L,Quest AF:E-cadherin is required for caveolin-1-mediated down-regulation of the inhibitor of apoptosis protein survivin via reduced beta-catenin-tcf/lef-dependent transcription.Mol Cell Biol 2007;27:7703-7717.
165 Ewan KB,Dale TC:The potential for targeting oncogenic wnt/beta-catenin signaling in therapy.Curr Drug Targets 2008;9:532-547.
166 Chen JS,Liang QM,Li HS,Yang J,Wang S,Long J W:Octreotide inhibits growth of colonic cancer sw480 cells by modulating the wnt/p-catenin pathway.Pharmazie 2009;64:126-131.
167 Ramakrishnan G,Lo Muzio L,Elinos-Baez CM,Jagan S,Augustine TA,Kamaraj S,Anandakumar P,Devaki T:Silymarin inhibited proliferation and induced apoptosis in hepatic cancer cells.Cell Prolif 2009;42:229-240.
168 Han A,Song Z,Tong C.,Hu D,Bi X,Augenlicht LH,Yang W:Sulindac suppresses betacatenin expression in human cancer cells.Eur J Pharmacol 2008;583:26-31.
169 Wang JS,Zheng CL,Wang YJ,Wen JF,Ren HZ,Liu Y,Jiang HY:Gene silencing of betacatenin by rnai inhibits cell proliferation in human esophageal cancer cells in vitro and in nude mice.Dis Esophagus 2009;22:151-162.
170 Zhao H,Cui Y,Dupont J,Sun H,Hennighausen L,Yakar S:Gverexpression of the tumor suppressor gene phosphatase and tensin homologue partially inhibits wnt-1-induced mammary tumorigenesis.Cancer Res 2005;65:6864-6873.
171 Dihlmann S,Klein S,Doeberitz Mv MK:Reduction of beta-catenin/t-cell transcription factor signaling by aspirin and indomethacin is caused by an increased stabilization of phosphorylated beta-catenin.Mol Cancer Ther 2003;2:509-516.
172 Rice PL.Kelloff J,Sullivan H,Driggers LJ,Beard KS,Kuwada S,Piazza G,Ahnen DJ:Sulindac metabolites induce caspase-and proteasome-dependent degradation of beta-catenin protein in human colon cancer cells.Mol Cancer Ther 2003;2:885-892.
173 Boon EM,Keller JJ,Wormhoudt TA,Giardiello FM,Offerhaus GJ,van der Neut R,Pals ST:Sulindac targets nuclear beta-catenin accumulation and wnt signalling in adenomas of patients with familial adenomatous polyposis and in human colorectal cancer cell lines.Br J Cancer 2004:90:224-229.
174 James LF,Panter KE,Gaffield W,Molyneux RJ:Biomedical applications of poisonous plant research.J Agric Food Chem 2004;52:3211-3230.
175 Chen X,Horiuchi A,Kikuchi N,Osada R,YoshidaJ,ShiozawaT,Konishi 1:Hedgehog signal pathway is activated in ovarian carcinomas,correlating with cell proliferation:It's inhibition leads to growth suppression and apoptosis.Cancer Sci 2007;98:68-76.
176 Chen JK,Taipale J,Cooper MK,Beachy PA:Inhibition of hedgehog signaling by direct binding of cyclopamine to smoothened.Genes Dev 2002;16:2743-2748.
177 Yilmaz OH,Valdez R,Theisen BK,Guo W,Ferguson DO,Wu H,Morrison SJ:Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells.Nature 2006;441:475-482.
178 Tsimberidou AM,Giles FJ,Estey E,O'Brien S,Keating MJ,KantarjianHM:The role of gemtuzumab ozogamicin in acute leukaemia therapy.Br J Haematol 2006;132:398-409.
179 Sperr WR,Florian S,Hauswirth AW,Valent P:Cd 33 as a target of therapy in acute myeloid leukemia:Current status and future perspectives.Leuk Lynon-SPhoma2005;46:1115-1120.
180 Moserle L,Indraccolo S,Ghisi M,Frasson C.,Fortunato E,Canevari S,Miotti S,Tosello V.Zamarchi R,Corradin A,Minuzzo S,Rossi E,Basso G,Amadori A:The side population of ovarian cancer cells is a primary target of ifh-alpha antitumor effects.Cancer Res 2008;68:5658-5668.
181 Sarkar FH,Li Y:Using chemopreventive agents to enhance the efficacy of cancer therapy.Cancer Res 2006;66:3347-3350.
182 Sun SY,Hail N,Jr.,Lotan R:Apoptosis as a novel target for cancer chemoprevention.J Natl Cancer Inst 2004;96:662-672.
183 Shay JW,Wright WE:Telomerase:A target for cancer therapeutics.Cancer Cell 2002;2:257-265.
184 Beachy PA.Karhadkar SS.Berman DM:Tissue repair and stem cell renewal in carcinogenesis.Nature 2004;432:324-331.
185 Aggarwal BB,Shishodia S,Sandur SK,Pandey MK,Sethi G:Inflammation and cancer:How hot is the link? Biochem Pharmacol 2006;72:1605-1621.
186 Mimeault M,Batra SK:Recent advances on multiple tumorigenic cascades involved in prostatic cancer progression and targeting therapies.Carcinogenesis 2006;27:1-22.
187 Mimeault M,Batra SK:Concise review:Recent advances on the significance of stem cells in tissue regeneration and cancer therapies.Stem Cells 2006;24:2319-2345.
188 Trosko JE,Tai MH:Adult stem cell theory of the multi-stage,multi-mechanism theory of carcinogenesis:Role of inflammation on the promotion of initiated stem cells.Contrib Microbiol 2006;13:45-65.
189 Arora A,Scholar EM:Role of tyrosine kinase inhibitors in cancer therapy.J Pharmacol Exp Ther 2005;315:971-979.
190 Warrell RP.Jr..de The H,Wang ZY,Degos L:Acute promyelocyte leukemia.N Engl J Med 1993;329:177-189.
191 Piccirillo SG,Reynolds BA,Zanetti N,Lamorte G,Binda E,Broggi G,Brem H,Olivi A, Dimeco F,Vescovi AL:Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells.Nature 2006;444:761-765.
192 Jain M,Arvanitis C,Chu K,Dewey W,Leonhardt E,Trinh M,Sundberg CD,Bishop JM,Felsher DW:Sustained loss of a neoplastic phenotype by brief inactivation of myc.Science 2002;297:102-104.
193 王建伟:人参总皂苷对cd 34+造血干/祖细胞体外扩增和分化的作用及机制研究.重庆,重庆医科大学,2004 pp 61.
194 高月,马增春,谭洪玲:四物汤及其提取物对辐射致血虚证小鼠造血作用的研究.天津中医药2003;20:1.
195 刘丹:同基因骨髓移植小鼠骨髓细胞pecam21(cd31)分子表达与川芎嗪促进造血重建作用的研究.武汉,华中科技大学,2004,pp21.
196 刘晓,武正炎,范萍:黄芪与粒细胞---集落刺激因子对外周血干细胞移植术后早期造血功能重建影响的观察.南京医科大学学报2000;20:4.
197 刘柏炎,蔡光先:补阳还五汤对低糖低氧损伤神经干细胞移行分化的影响.中国药物与临床2005 5:3.
198 孙晋浩,杨琳,高英茂:补阳还五汤对神经干细胞生长分化的影响.山东大学学报(医学版)2002;10:3.
199 张密霞,李越,杜嵘,张艳军:黄岑苷对体外培养神经干细胞分化的影响.天津中医药大学学报 2007;26:3.
200 刘建军,姚忠祥,秦茂林:单味黄芪红花丹参注射对神经干细胞分化影响的初步研究.第三军医大学学报2006;28:3.
201 黎晖,周健洪,陈东风:龟板对大鼠骨髓间充质干细胞向成骨分化的影响.中药新药与临床药理2005;16:3.
202 赛音其木格,娜仁图娅,杨健:大黄素诱导人骨髓间充质干细胞向成骨细胞分化的研究.中国中西医结合外科杂志2006;12:5.
203 杨忠奇,冼绍祥.汪朝晖:三七总皂苷对骨髓间充质干细胞分化为心肌样细胞的作用.中药新药与临床药理2006;17:4.
204 肖鲁伟,武中庆,季卫锋:右归饮诱导胎兔骨髓基质细胞向软骨细胞分化的实验研究.中国中医药科技2005;12:2.
205 姚晓黎,刘卫彬,柳太云:参芪液对成人骨髓间质干细胞的诱导分化作用.中国神经精 神疾病杂志2004;30:2.
206 刘金保,董晓先,董燕湘:多种中药成分诱导大鼠骨髓间质干细胞转变为神经元样细胞.中国药物与临床2003;3:3.
207 余勤,连俊兰,郭莹;丹参注射液诱导大鼠骨髓间充质干细胞分化为神经元样细胞的实验研究.中国中西医结合急救杂志2006;13:4.
208 杨立业,刘相名.惠国桢:丹参诱导鼠骨髓间充质细胞向神经元分化.中华神经外科疾病研究杂志 2003;2:4.
209 撒亚莲,李海标:川芎嗪诱导大鼠骨髓间质干细胞分化为神经元样细胞的研究.解剖学报 2003;34:4.
210 黄慧,唐云安,张成:香丹注射液定向诱导大鼠骨髓间质细胞分化为神经元样细胞.中药材2004;27:4.
211 Nelson WJ,Nusse R:Convergence of wnt,beta-catenin,and cadherin pathways.Science 2004;303:1483-1487.
212 Bienz M:Tcf:Transcriptional activator or repressor? Curr Opin Cell Biol 1998;10:366-372.
213 Loontiens FG,Regenfuss P,Zechel A,Dumortier L,Clegg RM:Binding characteristics of hoechst 33258 with calf thymus DNA,poly[d(a-t)],and d(ccggaattccgg):Multiple stoichiometries and determination of tight binding with a wide spectrum of site affinities.Biochemistry 1990;29:9029-9039.
214 Amdt-Jovin DJ,JovinTM:Analysis and sorting of living cells according to deOMribonucleic acid content.J Histochem Cytochem 1977;25:585-589.
215 Gregoire M,Hernandez-Verdun D,Bouteille M:Visualization of chromatin distribution in living pto cells by hoechst 33342 fluorescent staining.Exp Cell Res 1984;152:38-46.
216 Kim JB,Lee KM,Ko E,Han W,Lee JE,Shin I,Bae JY,Kim S,Noh DY:Berberine inhibits growth of the breast cancer cell lines mcf-7 and mda-mb-231.Planta Med 2008;74:39-42.
217 Zou J,Ran ZH,Xu Q,Xiao SD:Experimental study of the killing effects of OM on human colon cancer cell line sw 1116.Chin J Dig Dis 2005;6:15-20.
218 汤铭新.余桂清,段凤舞:中医扶正培本方药的抗肿瘤实验研究.癌症进展杂志1986
219 中国中医研究院广安门医院胃癌协作组:健牌益肾法对胃肠道癌术后化疗反应的临床及实验观察.河北医药1982
220 李杰,林洪生,孙桂芝:中医药治疗肿瘤研究现状的反思及展望.中医约学刊2005;23:3.
221 唐晓颇,孙桂芝,吴洁:健脾补肾方对胃癌细胞系mgc.803线粒体膜电位和细胞内活性氧的影响.中国实验方剂学杂志 2005;11:4.
222 王宁生,雷燕,刘平:关于血清药理学的思考.中国中西医结合杂志1999;19:1.
223 李军昌,夏天,黄熙:中药复方数理的研究工具.血清药理学.中药药理与临床199814:1.
224 张红敏,谢春光,陈世伟:含药血清体外药理试验的评价.中国中西医结合杂志 200424:1.
225 王建华,张永祥:中药药理与临床研究进展.北京,军事医学科学出版社,2002.
226 蒙一纯,丁霞,贲长恩:中药血清药理学应用研究展望.北京中医药大学学报 1999;22:2.
227 杨秀荣,郝美荣:中药成分代谢分析.中药成分代谢分析.
228 刘成海:中药复方体外药效学研究思考.中药新药与临床药理2000;11:3.
229 张群豪,蓓钟,陈可冀:用血消药理学方法观察血府逐瘀汤浓缩丸对实验性动脉粥样硬化家兔主动脉平滑肌细胞增殖的影响.中国中西医结合杂志1996 16:1.
230 李仪奎:中药血清药理学实验方法的若干问题.中药新约与临床药理1999;10:1.
231 贺玉琢:日本汉方药“血清药理学”、“血清药化学”的研究概况.国外医学·中医中药分册1998;20:1.
232 郑建军,吴新华,张再跃:十全大补汤对肿瘤患者放化疗减毒作用的观察.山东中医杂志 2000;19:1.
233 毛小娟:红芪和黄芪多糖的免疫调节作用.中华微生物和免疫学杂志1998;8:1.
234曾雪渝:香姑胞内糖、胞外糖对正常小鼠免疫功能的影响.中草药1985;16:1.
235 王亚平,祝彼得:当归多糖对造血祖细胞调控机理研究.中华医学杂志1996;76:1.
236 敏郑,王亚平:中药多糖抗肿瘤的药理学研究进展.国外医学·中医中药分册2000;22:1.
237 周金黄:中药现代化主要问题思考.中药药理与临床1998;14:1.
238 浩姜,樊光华.李全忠:人参皂甙激活恶性胸水中的tils及其与吉西他滨协同抗癌作用的实验研究[南华大学学报(医学版2002;30:1.
239 周志文:枸杞子多糖对小鼠骨髓造血干细胞、粒单系祖细胞增殖分化的影响.中药药理学毒理学杂志1991;5:1.
240 Knoblich JA:Mechanisms of asymmetric stem cell division.Cell 2008;132:583-597.
241 Yang L,Wang L,Geiger H,Cancelas JA,Mo J,Zheng Y:Rho gtpase cdc42 coordinates hematopoietic stem cell quiescence and niche interaction in the bone marrow.Proc Natl Acad Sci U S A 2007;104:5091-5096.
242 Ishikawa F,Yoshida S,Saito Y,Hijikata A,Kitamura H,Tanaka S,Nakamura R,Tanaka T,Tomiyama H,Saito N,Fukata M,Miyamoto T,Lyons B,Ohshima K,Uchida N,Taniguchi S,Ohara O,Akashi K,Harada M,Shultz LD:Chemotherapy-resistant human ami stem cells home to and engraft within the bone-marrow endosteal region.Nat Biotechnol 2007;25:1315-1321.
243 Ao M,Franco OE,Park D,Raman D,Williams K,Hayward SW:Cross-talk between paracrine-acting cytokine and chemokine pathways promotes malignancy in benign human prostatic epithelium.Cancer Res 2007;67:4244-4253.
244 Mishra PJ,Humeniuk R,Medina DJ,Alexe G,Mesirov JP,Ganesan S,Glod JW,Banerjee D:,Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells.Cancer Res 2008;68:4331-4339.
245 Karnoub AE,Dash AB,Vo AP,Sullivan A,Brooks MW,Bell GW.Richardson AL,Polyak K,Tubo R,Weinberg RA:Mesenchymal stem cells within tumour stroma promote breast cancer metastasis.Nature 2007;449:557-563.
246 Ramasamy R,Lam EW,Soeiro 1,Tisato V.Bonnet D,Dazzi F:Mesenchymal stem cells inhibit proliferation and apoptosis of tumor cells:Inon-SPact on in vivo tumor growth.Leukemia 2007;21:304-310.
247 Dwyer RM,Potter-Beirne SM,Harrington KA,Lowery AJ,Hennessy E,Murphy JM,Barry FP.O'Brien T,Kerin MJ:Monocyte chemotactic protein-1 secreted by primary breast tumors stimulates migration of mesenchymal stem cells.Clin Cancer Res 2007;13:5020-5027.
248 Ren C.,Kumar S,Chanda D,Kallman L,Chen J,Mountz JD,Ponnazhagan S:Cancer gene therapy using mesenchymal stem cells expressing interferon-beta in a mouse prostate cancer lung metastasis model.Gene Ther 2008;15:1446-1453.
249 Djouad F,Plence P,Bony C.,Tropel P.Apparailly F,Sany J,Noel D,Jorgensen C:Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals.Blood 2003;102:3837-3844.
250 Ning H,Yang F.Jiang M,Hu L,Feng K,Zhang J,Yu Z,Li B? Xu C.,Li Y.Wang J,Hu J,Lou X,Chen H:The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients:Outcome of a pilot clinical study.Leukemia 2008;22:593-599.
2 Lapidot T,Sirard C,Vormoor J,al.e:A cell initiating human acute myeloid leukaemia after transplantation into scid mice.Nature 1994;367:4.
3 Reya T,Duncan AW,Ailles L,Domen J,Scherer DC,Willert K,Hintz L,Nusse R,Weissman IL:A role for wnt signalling in self-renewal of haematopoietic stem cells.Nature 2003;423:409-414.
4 Singh SK,Clarke ID,Hide T,Dirks PB:Cancer stem cells in nervous system tumors.Oncogene 2004;23:7267-7273.
5 Ponti D,Costa A,Zaffaroni N,Pratesi G,Petrangolini G,Coradini D,Pilotti S,Pierotti MA,Daidone MG:Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties.Cancer Res 2005;65:5506-5511.
6 Al-Hajj M,Wicha MS,Benito-Hernandez A,Morrison SJ,Clarke MF:Prospective identification of tumorigenic breast cancer cells.Proc Natl Acad Sci U S A 2003;100:3983-3988.
7 Taylor MD,Liu L,Raffel C,Hui CC,Mainprize TG,Zhang X,Agatep R,Chiappa S,Gao L,Lowrance A,Hao A,Goldstein AM,Stavrou T,Scherer SW,Dura WT,Wainwright B,Squire JA,Rutka JT.Hogg D:Mutations in sufu predispose to medulloblastoma.Nat Genet 2002;31:306-310.
8 Perez-Losada J,Balmain A:Stem-cell hierarchy in skin cancer.Nat Rev Cancer 2003:3:434-443.
9 Richardson GD,Robson CN,Lang SH,Neal DE,Maitland NJ,Collins AT:Cd 133,a novel marker for human prostatic epithelial stem cells.J Cell Sci 2004;117:3539-3545.
10 Collins AT,Berry PA,Hyde C,Stower MJ,Maitland NJ:Prospective identification of tumorigenic prostate cancer stem cells.Cancer Res 2005;65:10946-10951.
11 Seigel GM,Canon-SPbell LM,Narayan M,Gonzalez-Fernandez F:Cancer stem cell characteristics in retinoblastoma.Mol Vis 2005;11:729-737.
12 Li C,Heidt DG,Dalerba P.Burant CF,Zhang L,Adsay V:Wicha M,Clarke MF,Simeone DM:Identification of pancreatic cancer stem cells.Cancer Res 2007;67:l030-1037.
13 Fiegel HC,Gluer S,Roth B,Rischewski J,von Schweinitz D,Ure B,Lambrecht W.Kluth D:Stem-like cells in human hepatoblastoma.J Histochem Cytochem 2004;52:1495-1501.
14 Houghton J,Stoicov C.,Nomura S,Rogers AB,Carlson J,Li H,Cai X,Fox JG,Goldenring JR,Wang TC:Gastric cancer originating from bone marrow-derived cells.Science 2004;306:1568-1571.
15 Kim CF,Jackson EL,Woolfenden AE,Lawrence S,Babar I,Vogel S,Crowley D,Bronson RT,Jacks T:Identification of bronchioalveolar stem cells in normal lung and lung cancer.Cell 2005;121:823-835.
16 Setoguchi T,Taga T,Kondo T:Cancer stem cells persist in many cancer cell lines.Cell Cycle 2004;3:414-415.
17 Patrawala L,Calhoun T,Schneider-Broussard R,Zhou J,Claypool K,Tang DG:Side,population is enriched in tumorigenic,stem-like cancer cells,whereas abcg2+ and abcg2-cancer cells are similarly tumorigenic.Cancer Res 2005;65:6207-6219.
18 Kondo T,Setoguchi T,Taga T:Persistence of a small subpopulation of cancer stem-like cells in the c6 glioma cell line.Proc Natl Acad Sci U S A 2004;101:781-786.
19 Kucia M,Reca R,Miekus K,Wanzeck J,Wojakowski W,Janowska-Wieczorek A,Ratajczak J,Ratajczak MZ:Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms:Pivotal role of the sdf-l-cxcr4 axis.Stem Cells 2005;23:879-894.
20 Li L,Neaves WB:Normal stem cells and cancer stem cells:The niche matters.Cancer Res 2006;66:4553-4557.
21 Singh SK,Hawkins C.,Clarke ID,Squire JA,Bayani J,Hide T,Henkelman RM,Cusimano MD,Dirks PB:Identification of human brain tumour initiating cells.Nature 2004;432:396-401.
22 Leslie EM,Deeley RG,Cole SP:Multidrug resistance proteins:Role of p-glycoprotein,mrpl,mrp2,and bcrp(abcg2)in tissue defense.Toxicol Appl Pharmacol 2005;204:216-237.
23 Zhou S,Morris JJ,Barnes Y,Lan L,Schuetz JD,Sorrentino BP:Bcrpl gene expression is required for normal numbers of side population stem cells in mice,and confers relative protection to mitoxantrone in hematopoietic cells in vivo.Proc Natl Acad Sci U S A 2002;99:12339-12344.
24 Staud F,Pavek P:Breast cancer resistance protein(bcrp/abcg2).Int J Biochem Cell Biol 2005;37:720-725.
25 Dean M,Fojo T,Bates S:Tumour stem cells and drug resistance.Nat Rev Cancer 2005;5:275-284.
26 Polyak K,Hahn WC:Roots and stems:Stem cells in cancer.Nat Med 2006;! 2:296-300.
27 Kai T,Spradling A:Differentiating germ cells can revert into functional stem cells in drosophila melanogaster ovaries.Nature 2004;428:564-569.
28 Tsuji-Takayama K,Inoue T,Ijiri Y,Otani T,Motoda R,Nakamura S,Orita K:Demethylating agent,5-azacytidine,reverses differentiation of embryonic stem cells.Biochem Biophys Res Commun 2004;323:86-90.
29 von Melchner H,Hoffken K:Human placental conditioned medium reverses apparent commitment to differentiation of human promyelocytic leukemia cells(hl60).Blood 1985;66:1469-1472.
30 Pardal R,Clarke MF.Morrison SJ:Applying the principles of stem-cell biology to cancer.Nat Rev Cancer 2003;3:895-902.
31 Huntly BJ,Gilliland DG:Leukaemia stem cells and the evolution of cancer-stem-cell research.Nat Rev Cancer 2005;5:311-321.
32 Yamashita YM,Fuller MT,Jones DL:Signaling in stem cell niches:Lessons from the drosophila germline.J Cell Sci 2005;118:665-672.
33 Moore JC,Sumerel JL,Schnackenberg BJ,Nichols JA,Wikramanayake A,Wessel GM,Marzluff WF:Cyclin d and cdk4 are required for normal development beyond the blastula stage in sea urchin embryos.Mol Cell Biol 2002;22:4863-4875.
34 Niemann C:Controlling the stem cell niche:Right time,right place,right strength.Bioessays 2006;28:1-5.
35 Dontu G,Jackson KW,McNicholas E,Kawamura MJ,Abdallah WM,Wicha MS:Role of notch signaling in cell-fate determination of human mammary stem/progenitor cells.Breast Cancer Res 2004;6:R605-615.
36 Varjosalo M,Li SP,Taipale J:Divergence of hedgehog signal transduction mechanism between drosophila and mammals.Dev Cell 2006;10:177-186.
37 King TJ,DiBerardino MA:Transplantation of nuclei from the frog renal adenocarcinoma.I.Development of tumor nuclear-transplant embryos.Ann N Y Acad Sci 1965;126:115-126.
38 Serov O,Matveeva N,Kuznetsov S,Kaftanovskaya E,Mittmann J:Embryonic hybrid cells:A powerful tool for studying pluripotency and reprogramming of the differentiated cell chromosomes.An Acad Bras Cienc 2001;73:561 -568.
39 Feuring-Buske M,Frankel AE,Alexander RL,Gerhard B,Hogge DE:A diphtheria toxin- interleukin 3 fusion protein is cytotoxic to primitive acute myeloid leukemia progenitors but spares normal progenitors.Cancer Res 2002;62:1730-1736.
40 Jin L,Hope KJ,Zhai Q,Smadja-Joffe F,Dick JE:Targeting of cd44 eradicates human acute myeloid leukemic stem cells.Nat Med 2006;12:1167-1174.
41 Guzman ML,Swiderski CF,Howard DS,Grimes BA,Rossi RM,Szilvassy SJ,Jordan CT:Preferential induction of apoptosis for primary human leukemic stem cells.Proc Natl Acad Sci U S A 2002;99:16220-16225.
42 Recher C.,Beyne-Rauzy O,Demur C.,Chicanne G,Dos Santos C.,Mas VM,Benzaquen D,Laurent G,Huguet F,Payrastre B:Antileukemic activity of rapamycin in acute myeloid leukemia.Blood 2005;105:2527-2534.
43 Xu Q,Thonon-SPson JE,Carroll M:Mtor regulates cell survival after etoposide treatment in primary ami cells.Blood 2005;106:4261-4268.
44 Calabrese C.,Poppleton H,Kocak M,HoggTL,Fuller C.,Hamner B,Oh EY.Gaber MW,Finklestein D,Allen M,Frank A,Bayazitov IT,Zakharenko SS,Gajjar A,Davidoff A,Gilbertson RJ:A perivascular niche for brain tumor stem cells.Cancer Cell 2007:11:69-82.
45 高瑞兰：人参总皂甙对白血病祖细胞作用的实验观察．上海中医药杂志 1999；10：3．
46 Funayama N,Fagotto F,McCrea P,Gumbiner BM:Embryonic axis induction by the amiadiilo repeat domain of beta-catenin:Evidence for intracellular signaling.J Cell Biol 1995;128:959-968.
47 Balic M,Lin H,Young L,Hawes D,Giuliano A,McNamara G,Datar RH,Cote RJ:Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype.Clin Cancer Res 2006;12:5615-5621.
48 Kleber M,Sommer L:Wnt signaling and the regulation of stem cell function.Curr Opin Cell Biol 2004;16:681-687.
49 Kuhnert F,Davis CR,Wang HT,Chu P,Lee M,Yuan J,Nusse R,Kuo CJ:Essential requirement for wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of dickkopf-1.Proc Natl Acad Sci U S A 2004;101:266-271.
50 van Genderen C.,Okamura RM,Farinas I,Quo RG,Parslow TG,Bruhn L,Grosschedl R:Development of several organs that require inductive epithelial-mesenchymal interactions is inon-SPaired in lef-1-deficient mice.Genes Dev 1994;8:2691-2703.
51 Teuliere J,Faraldo MM,Deugnier MA,Shtutman M,Ben-Ze'ev A,Thiery JP,Glukhova MA: Targeted activation of beta-catenin signaling in basal mammary epithelial cells affects mammary development and leads to hyperplasia.Development 2005;132:267-277.
52 Gregorieff A,Clevers H:Wnt signaling in the intestinal epithelium:From endoderm to cancer.Genes Dev 2005;19:877-890.
53 Kinzler KW,VogelsteinB:Life(and death)in a malignant tumour.Nature 1996;379:19-20.
54 Lu D,Zhao Y,Tawatao R,Cottam HB,Sen M,Leoni LM,Kipps TJ,Corr M,Carson DA:Activation of the wnt signaling pathway in chronic lynon-SPhocytic leukemia.Proc Natl Acad Sci USA 2004;101:3118-3123.
55 McWhirter JR,Neuteboom ST,Wancewicz EV,Monia BP.Downing JR,Murre C:Oncogenic homeodomain transcription factor e2a-pbxl activates a novel wnt gene in pre-b acute lynon-SPhoblastoid leukemia.Proc Natl Acad Sci U S A 1999;96:11464-11469.
56 Breuhahn K,Longerich T,Schirmacher P:Dysregulation of growth factor signaling in human hepatocellular carcinoma.Oncogene 2006;25:3787-3800.
57 Jin LH,Shao QJ,Luo W,Ye ZY,Li Q,Lin SC:Detection of point mutations of the axinl gene in colorectal cancers.Int J Cancer 2003:107:696-699.
58 Bafico A,Liu G,Goldin L,Harris V.Aaronson SA:An autocrine mechanism for constitutive wnt pathway activation in human cancer cells.Cancer Cell 2004;6:497-506.
59 Brabletz T,Jung A,Hermann K,Gunther K,Hohenberger W,Kirchner T:Nuclear overexpression of the oncoprotein beta-catenin in colorectal cancer is localized predominantly at the invasion front.Pathol Res Pract 1998;194:701-704.
60 Brabletz T,Jung A,Reu S,Porzner M,Hlubek F,Kunz-Schughart LA,Knuechel R,Kirchner T:Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment.Proc Natl Acad Sci U S A 2001;98:10356-10361.
61 Kirchner T,Brabletz T:Patterning and nuclear beta-catenin expression in the colonic adenoma-carcinoma sequence.Analogies with embryonic gastrulation.Am J Pathol 2000;157:1113-1121.
62 Janssen KP.Alberici P.Fsihi H,Gaspar C.,Breukel C.,Franken P.Rosty C.,Abal M,El Marjou F.Smits R,Louvard D,Fodde R,Robine S:Ape and oncogenic kras are synergistic in enhancing wnt signaling in intestinal tumor formation and progression.Gastroenterology 2006;131:1096-1109.
63 Shulewitz M,Soloviev I,Wu T,Koeppen H,Polakis P,SakanakaC:Repressor roles for tcf-4 and sfrpl in wnt signaling in breast cancer.Oncogene 2006;25:4361-4369.
64 Lin S Y,Xia W,Wang JC.,Kwong KY,Spohn B,Wen Y,Pestell RG,Hung MC:Beta-catenin,a novel prognostic marker for breast cancer:Its roles in cyclin d1 expression and cancer progression.Proc Natl Acad Sci U S A 2000;97:4262-4266.
65 Ormestad M,Astorga J,Landgren H,Wang T,Johansson BR,Miura N,Carlsson P:Foxfl and foxf2 control murine gut development by limiting mesenchymal wnt signaling and promoting extracellular matrix production.Development 2006;133:833-843.
66 Rasola A,Fassetta M,De Bacco F,D'Alessandro L,Gramaglia D,Di Renzo MF,Comoglio PM:A positive feedback loop between hepatocyte growth factor receptor and beta-catenin sustains colorectal cancer cell invasive growth.Oncogene 2007;26:1078-1087.
67 Yang L,Lin C.,Liu ZR:P68 rna helicase mediates pdgf-induced epithelial mesenchymal transition by displacing axin from beta-catenin.Cell 2006;127:139-155.
68 Brown JR,DuBois RN:Cox-2:A molecular target for colorectal cancer prevention.J Clin Oncol 2005;23:2840-2855.
69 Castellone MD,Teramoto H,Williams BO,Druey KM,Gutkind JS:Prostaglandin e2 promotes colon cancer cell growth through a gs-axin-beta-catenin signaling axis.Science 2005;310:1504-1510.
70 Smith K,Bui TD,Poulsom R,Kaklamanis L,Williams G,Harris AL:Up-regulation of macrophage wnt gene expression in adenoma-carcinoma progression of human colorectal cancer.Br J Cancer 1999;81:496-502.
71 Eswarakumar VP,Lax I,Schlessinger J:Cellular signaling by fibroblast growth factor receptors.Cytokine Growth Factor Rev 2005;16:139-149.
72 Katoh M:Fgf signaling network in the gastrointestinal tract(review).Int J Oncol 2006;29:163-168.
73 Katoh M:Epithelial-mesenchymal transition in gastriG cancer(review).Int J Oncol 2005;27:1677-1683.
74 Katoh M:Notch signaling in gastrointestinal tract(review).Int J Oncol 2007;30:247-251.
75 Katoh Y,Katoh M:Hedgehog signaling pathway and gastrointestinal stem cell signaling network(review).Int J Mol Med 2006;18:1019-1023.
76 Katoh Y,Katoh M:Wnt antagonist,sfrpl,is hedgehog signaling target.Int J Mol Med 2006;17:171-175.
77 Katoh M:Networking of wnt,fgf,notch,bnon-SP,and hedgehog signaling pathways during carcinogenesis.Stem Cell Rev 2007;3:30-38.
78 Harris GJ,Senagore AJ,Lavery IC,Church JM,Fazio VW:Factors affecting survival after palliative resection of colorectal carcinoma.Colorectal Dis 2002;4:31-35.
79 Couzin J:Medicine.Tracing the steps of metastasis,cancer's menacing ballet.Science 2003;299:1002-1006.
80 Zhang J,Niu C,Ye L,Huang H,He X,Tong WG,Ross J,Haug J,Johnson T,Feng JQ,Harris S,Wiedemann LM,Mishina Y,Li L:Identification of the haematopoietic stem cell niche and control ofthe niche size.Nature 2003;425:836-841.
81 Lowry WE,Blanpain C,Nowak JA,Guasch G,Lewis I,Fuchs E:Defining the inon-SPact of beta-catenin/tcf transactivation on epithelial stem cells.Genes Dev 2005;19:1596-1611.
82 Heissig B,Hattori K,Dias S,Friedrich M,Ferris B,Hackett NR,Crystal RG,Besmer P,Lyden D,Moore MA,Werb Z,Rafii S:Recruitment of stem and progenitor cells from the bone marrow niche requires mnon-SP-9 mediated release of kit-ligand.Cell 2002;109:625-637.
83 Curran S,Murray GI:Matrix metalloproteinases in tumour invasion and metastasis.J Pathol 1999:189:300-308.
84 Crowe DL,Ohannessian A:Recruitment of focal adhesion kinase and paxillin to betal integrin promotes cancer cell migration via mitogen activated protein kinase activation.BMC Cancer 2004;4:18.
85 Kang H,Watkins G,Douglas-Jones A,Mansel RE,Jiang WG:The elevated level of cxcr4 is correlated with nodal metastasis of human breast cancer.Breast 2005;14:360-367.
86 Venezia TA,Merchant AA,Ramos CA.Whitehouse NL,Young AS,Shaw CA,Goodell MA:Molecular signatures of proliferation and quiescence in hematopoietic stem cells.PLoS Biol 2004;2:e301.
87 Cairns J:The cancer problem.Sci Am 1975;233:64-72,77-68.
88 Wang S,Yang D,Lippman ME:Targeting bcl-2 and bcl-xl with nonpeptidic small-molecule antagonists.Semin Oncol 2003;30:133-142.
89 Graham SM,Jorgensen HG,Allan E,Pearson C,Alcorn MJ,Richmond L,Holyoake TL:Primitive,quiescent,philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to sti571 in vitro.Blood 2002;99:319-325.
90 Paget S:The distribution of secondary growths in cancer of the breast.1889.Cancer Metastasis Rev 1989;8:98-101.
91 Tu SM,Lin SH,Logothetis CJ:Stem-cell origin of metastasis and heterogeneity in solid tumours.Lancet Oncol 2002;3:508-513.
92 Jamieson CH,Ailles LE,Dylla SJ,Muijtjens M,Jones C,Zehnder JL,Gotlib J,Li K,Manz MG,Keating A,Sawyers CL,Weissman IL:Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis cml.N Engl J Med 2004;351:657-667.
93 Korinek V,Barker N,Morin PJ,van Wichen D,de Weger R,Kinzler KW,Vogelstein B,Clevers H:Constitutive transcriptional activation by a beta-catenin-tcf conon-SPlex in ape-/-colon carcinoma.Science 1997;275:1784-1787.
94 Gat U,DasGupta R,Degenstein L,Fuchs E:De novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin.Cell 1998;95:605-614.
95 Ming Kwan K,Li AG,Wang XJ,Wurst W,Behringer RR:Essential roles of bnon-SPr-ia signaling in differentiation and growth of hair follicles and in skin tumorigenesis.Genesis 2004;39:10-25.
96 He XC,Zhang J,Tong WG,Tawfik O,Ross J,Scoville DH,Tian Q,Zeng X,He X,Wiedemann LM,Mishina Y,Li L:Bnon-SP signaling inhibits intestinal stem cell self-renewal through suppression of wnt-beta-catenin signaling.Nat Genet 2004;36:1117-1121.
97 Dubey P,Wu H,Reiter RE,Witte ON:Alternative pathways to prostate carcinoma activate prostate stem cell antigen expression.Cancer Res 2001;61:3256-3261.
98 Gao CL,Dean RC,Pinto A,Mooneyhan R,Connelly RR,McLeod DG,Srivastava S,Moul JW:Detection of circulating prostate specific antigen expressing prostatic cells in the bone marrow of radical prostatectomy patients by sensitive reverse transcriptase polymerase chain reaction.J Urol 1999;161:1070-1076.
99 林洪生,李树奇,朴炳奎:中医复方对肺癌患者抑瘤抗转移作用的研究.中国中西医结合外科杂志1998;4:3.
100 刘嘉湘,施志明,徐振晔:滋阴生津益气升阳法 治疗晚期原发性肺癌的临床研究.中医杂志 1995;36:4.
101 林洪生:中医药防治肿瘤复发与转移的研究概况.医学理论与实践 1999;12:5.
102 林洪生,彩虹,黄启福:金安粉针剂对肺癌细胞系超微结构的影响.中国病理生理杂志2004;20:6.
103 娄金丽,邱全瑛.林洪生:小檗碱对人胃癌细胞增殖、细胞周期及cd44v6 表达的影响.中国免疫学杂志 2004;20:3.
104 张永健:复方中药注射液对人肝癌细胞体外杀伤效应及其对细胞周期的影响.中西医结合杂志1989;9:2.
105 徐建国,任连生,马俊英:302种传统治癌中草药水提液对h1 260细胞的诱导分化及细胞毒作用.山西医学杂志 1991;20:1.
106 司维柯,韩风,秦建华:苦参提取液诱导k562细胞分化的细胞化学观察.中国组织化学与细胞化学杂志,1997;6:1.
107 翁玲,刘学英,刘彦:黄芪多糖对小鼠骨髓及外周血造血干细胞的增殖及动员作用.基础医学与临床2003;23:4.
108 徐传毅,何伟.方斌:生脉成骨方对股骨头坏死i型胶原表达的调节作用研究.现代中西医结合杂志2003;6:3.
109 张艳军,范祥.胡利民:不同治则中药单体对体外培养神经干细胞分化的影响.天津中医药2004;21:2.
110 吴理茂,张荣利,刘红:展望中药在心肌细胞移植中的作用.中国中西医结合杂志2003;23:3.
111 Ricci-Vitiani L,Lombardi DG,Pilozzi E,Biffoni M,Todaro M,Peschle C,De Maria R:Identification and expansion of human colon-cancer-initiating cells.Nature 2007;445:111-115.
112 WuC,Alman BA:Side population cells in human cancers.Cancer Lett 2008;268:1-9.
113 Dontu G,Wicha MS:Survival of mammary stem cells in suspension culture:Incn-SPlications for stem cell biology and neoplasia.J Mammary Gland Biol Neoplasia 2005;10:75-86.
114 Goodell MA,Brose K,Paradis G,Conner AS,Mulligan RC:Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo.J Exp Med 1996:183:1797-1806.
115 Alvi AJ,Clayton H,Joshi C,Enver T,Ashworth A,Vivanco MM,Dale TC,Smalley MJ:Functional and molecular characterisation of mammary side population cells.Breast Cancer Res 2003;5:R1-8.
116 Donnenberg VS,Landreneau RJ,Donnenberg AD:Tumorigenic stem and progenitor cells:Inon-SPlications for the therapeutic index of anti-cancer agents.J Control Release 2007;122:385-391.
117 Hirschmann-Jax C.,Foster AE,Wulf GG,Nuchtern JG,Jax TW,Gobel U,Goodell MA,Brenner MK:A distinct“Side population”Of cells with high drug efflux capacity in human tumor cells.Proc Natl Acad Sci U S A 2004;101:14228-14233.
118 Haraguchi N,UtsunomiyaT,Inoue H,Tanaka F,Mimori K,Barnard GF,Mori M:Characterization of a side population of cancer cells from human gastrointestinal system.Stem Cells 2006;24:506-513.
119 Wang J,Guo LP,Chen LZ,Zeng YX,Lu SH:Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line.Cancer Res 2007;67:3716-3724.
120 Ho MM,Ng AV,Lam S,Hung J Y:Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells.Cancer Res 2007;67:4827-4833.
121 ChibaT.Kita K,Zheng Y W.Yokosuka O,Saisho H,lwama A,Nakauchi H,Taniguchi H:Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties.Hepatology 2006;44:240-251.
122 Szotek PP,Pieretti-Vanmarcke R,Masiakos PT.Dinulescu DM,Connolly D,Foster R,Dombkowski D,Preffer F,Maclaughlin DT,Donahoe PK:Ovarian cancer side population defines cells with stem cell-like characteristics and mullerian inhibiting substance responsiveness.Proc Natl Acad Sci U S A 2006;103:11154-11159.
123 Telford WG,Frolova EG:Discrimination of the hoechst side population in mouse bone marrow with violet and near-ultraviolet laser diodes.Cytometry A 2004;57:45-52.
124 Liu Y,Lu WL,Guo J,Du J,Li T,Wu JW,Wang GL,Wang JC.,Zhang X,Zhang Q:A potential target associated with both cancer and cancer stem cells:A combination therapy for eradication of breast cancer using vinorelbine stealthy liposomes plus parthenolide stealthy liposomes.J Control Release 2008;129:18-25.
125 Farnie G,Clarke RB:Mammary stem cells and breast cancer—role of notch signalling.Stem Cell Rev 2007;3:169-175.
126 Kim M,Turnquist H,Jackson J,Sgagias M,Yan Y,Gong M,Dean M,Sharp JG,Cowan K:The multidrug resistance transporter abcg2(breast cancer resistance protein 1)effluxes hoechst 33342 and is overexpressed in hematopoietic stem cells.Clin Cancer Res 2002;8:22-28.
127 Hu C,Li H,Li J,Zhu Z,Yin S,Hao X,Yao M,Zheng S,Gu J:Analysis of abcg2 expression and side population identifies intrinsic drug efflux in the hcc cell line mhcc-971 and its modulation by akt signaling.Carcinogenesis 2008;29:2289-2297.
128 She JJ,Zhang PG,Wang ZM,Gan WM,Che XM:Identification of side population cells from bladder cancer cells by dyecycle violet staining.Cancer Biol Ther 2008;7:1663-1668.
129 Li Y,Welm B,Podsypanina K,Huang S,Chamorro M,Zhang X,Rowlands T,Egeblad M,Cowin P.Werb Z,Tan LK,Rosen JM,Varmus HE:Evidence that transgenes encoding conon-SPonents of the wnt signaling pathway preferentially induce mammary cancers from progenitor cells.ProcNatl Acad Sci USA2003;100:15853-15858.
130 Liu BY,McDermott SP,Khwaja SS,Alexander CM:The transforming activity of wnt effectors correlates with their ability to induce the accumulation of mammary progenitor cells.Proc Natl Acad Sci USA 2004;101:4158-4163.
131 Shackleton M,Vaillant F.Sinon-SPson KJ,Stingl J,Smyth GK,Asselin-Labat ML,Wu L,Lindeman GJ,Visvader JE:Generation of a functional mammary gland from a single stem cell.Nature 2006;439:84-88.
132 李志琴,章静波:细胞周期调控与肿瘤.癌症进展杂志2004;2:6.
133 Imbert A,Eelkema R,Jordan S,Feiner H,Cowin P:Delta n89 beta-catenin induces precocious development,differentiation,and neoplasia in mammary gland.J Cell Biol 2001;153:555-568.
134 Packham G,Cleveland JL:C-mycand apoptosis.Biochim Biophys Acta 1995;1242:11-28.
135 Hoffman B,Liebermann DA:Apoptotic signaling by c-myc.Oncogene 2008;27:6462-6472.
136 Dang CV:C-myc target genes involved in cell growth,apoptosis,and metabolism.Mol Cell Biol 1999;19:1-11.
137 Dang CV,Resar LM,Emison E,Kim S,Li Q,Prescott JE,Wonsey D,Zeller K:Function of the c-myc oncogenic transcription factor.Exp Cell Res 1999;253:63-77.
138 Elend M,Eilers M:Cell growth:Downstream of myc-to grow or to cycle?Curr Biol 1999;9:R936-938.
139 Prendergast GC:Mechanisms of apoptosis by c-myc.Oncogene 1999;18:2967-2987.
140 Guerin M,Barrois M,Terrier MJ,Spielmann M,Riou G:Overexpression of either c-myc or cerbb-2/neu proto-oncogenes in human breast carcinomas:Correlation with poor prognosis. Oncogene Res 1988;3:21-31.
141 Mariani-Costantini R,Escot C,Theillet C,Gentile A,Merlo G,Lidereau R,Callahan R:In situ c-myc expression and genomic status of the c-myc locus in infiltrating ductal carcinomas of the breast.Cancer Res 1988;48:199-205.
142 Tervahauta AI,Syrjanen SM,Kallio PJ,Syrjanen KJ:Immunohistochemistry,in situ hybridization and polymerase chain reaction(pcr) in detecting c-myc expression in human malignancies.Anticancer Res 1992;12:1005-1011.
143 Sandgren EP,Luetteke NC,Palmiter RD,Brinster RL,Lee DC:Overexpression of tgf alpha in transgenic mice:Induction of epithelial hyperplasia,pancreatic metaplasia,and carcinoma of the breast.Cell 1990;61:1121-1135.
144 Ozaki S,Ikeda S,Ishizaki Y,Kurihara T,Tokumoto N,Iseki M,Arihiro K,Kataoka T,Okajima M,Asahara T:Alterations and correlations of the conon-SPonents in the wnt signaling pathway and its target genes in breast cancer.Oncol Rep 2005;14:1437-1443.
145 Cowling VH,D'Cruz CM,Chodosh LA,Cole MD:C-myc transforms human mammary epithelial cells through repression of the wnt inhibitors dkkl and sfrpl.Mol Cell Biol 2007;27:5135-5146.
146 陶上乘,王静珍:苦豆子生物碱的药理作用.中国药学杂志 1992;27:4.
147 李先荣,刘德宽:苦参生物碱抗小鼠移植性肿瘤研究.中西医结合杂志1982;2:1.
148 王秀坤,李家实:白刺花生物碱的体外抑瘤作用.北京中医药大学学报1996;19:2.
149 张燕军,夏天,赵建斌.:苦参碱对smmc-7721细胞系的诱导分化作用.第四军医大学学报1998;19:4.
150 程光,章翔,费舟:苦参碱对bt325胶质瘤细胞的增殖抑制和诱导凋亡作用.第四军医大学学报;23:3.
151 张百红,岳红云,李新民:苦参碱抗癌作用与诱导肿瘤细胞凋亡.肿瘤研究与临床1999;12:2.
152 Lindenboim L,Diamond R,Rothenberg E,Stein R:Apoptosis induced by serum deprivation of pc 12 cells is not preceded by growth arrest and can occur at each phase of the cell cycle.Cancer Res 1995;55:1242-1247.
153 李龙江,陈志琼.郑元义:氧化苦参碱对人卵巢癌细胞skov-3体外活性的影响.重庆医科大学学报2003;17:2.
154 侯华新,黎丹戎,栾英姿:氧化苦参碱诱导卵巢癌skov-3细胞凋亡作用的实验研究[中国药理学通报2002;18:4.
155 王兵,王国俊,徐均:氧化苦参碱对肿瘤诱导血管内皮细胞增殖的抑制作用.实用肿瘤杂志 2000;15:4.
156 许相儒,蒋纪恺:苦参及其生物碱抗肿瘤活性研究进展.中国中西医结合杂志199818:3.
157 田涛,吴朝晖,金惠铭:原位末端标记(tunel)法、流式细胞仪pi法和pi,annexin v双标记法检测细胞凋亡的比较.中国微循环1999;3:5.
158 司徒镇强,吴军正(eds):细胞培养.ed.西安,世界图书出版社,1996,vol第一版,pp 135.
159 Jin Y,Hu J,Wang Q,Li Z,Chen Y:Effects of OM on the apoptosis of human esophageal carcinoma eca109 cell line and its mechanism.J Huazhong Univ Sci Technolog Med Sci 2008:28:314-316.
160 Song MQ,Zhu JS,Chen JL,Wang L,Da W,Zhu L,Zhang WP:Synergistic effect of OM and angiogenesis inhibitor nm-3 on modulating apoptosis in human gastric cancer cells.World J Gastroenterol 2007;13:1788-1793.
161 Song G,Luo Q,Qin J,Wang L,Shi Y,Sun C:Effects of OM on proliferation and apoptosis in human hepatoma cells.Colloids Surf B Biointerfaces 2006;48:1-5.
162 Wieczorek M,Paczkowska A,Guzenda P.Majorek M,Bednarek AK,Lanon-SParska-Przybysz M:Silencing of wnt-1 by sirna induces apoptosis of mcf-7 human breast cancer cells.Cancer Biol Ther 2008;7:268-274.
163 Huang WS,Wang JP,Wang T,Fang JY,Lan P,Ma JP:Shma-mediated gene silencing of betacatenin inhibits growth of human colon cancer cells.World J Gastroenterol 2007;13:6581-6587.
164 Torres VA,Tapia JC,Rodriguez DA,Lladser A,Arredondo C,Leyton L,Quest AF:E-cadherin is required for caveolin-1-mediated down-regulation of the inhibitor of apoptosis protein survivin via reduced beta-catenin-tcf/lef-dependent transcription.Mol Cell Biol 2007;27:7703-7717.
165 Ewan KB,Dale TC:The potential for targeting oncogenic wnt/beta-catenin signaling in therapy.Curr Drug Targets 2008;9:532-547.
166 Chen JS,Liang QM,Li HS,Yang J,Wang S,Long J W:Octreotide inhibits growth of colonic cancer sw480 cells by modulating the wnt/p-catenin pathway.Pharmazie 2009;64:126-131.
167 Ramakrishnan G,Lo Muzio L,Elinos-Baez CM,Jagan S,Augustine TA,Kamaraj S,Anandakumar P,Devaki T:Silymarin inhibited proliferation and induced apoptosis in hepatic cancer cells.Cell Prolif 2009;42:229-240.
168 Han A,Song Z,Tong C.,Hu D,Bi X,Augenlicht LH,Yang W:Sulindac suppresses betacatenin expression in human cancer cells.Eur J Pharmacol 2008;583:26-31.
169 Wang JS,Zheng CL,Wang YJ,Wen JF,Ren HZ,Liu Y,Jiang HY:Gene silencing of betacatenin by rnai inhibits cell proliferation in human esophageal cancer cells in vitro and in nude mice.Dis Esophagus 2009;22:151-162.
170 Zhao H,Cui Y,Dupont J,Sun H,Hennighausen L,Yakar S:Gverexpression of the tumor suppressor gene phosphatase and tensin homologue partially inhibits wnt-1-induced mammary tumorigenesis.Cancer Res 2005;65:6864-6873.
171 Dihlmann S,Klein S,Doeberitz Mv MK:Reduction of beta-catenin/t-cell transcription factor signaling by aspirin and indomethacin is caused by an increased stabilization of phosphorylated beta-catenin.Mol Cancer Ther 2003;2:509-516.
172 Rice PL.Kelloff J,Sullivan H,Driggers LJ,Beard KS,Kuwada S,Piazza G,Ahnen DJ:Sulindac metabolites induce caspase-and proteasome-dependent degradation of beta-catenin protein in human colon cancer cells.Mol Cancer Ther 2003;2:885-892.
173 Boon EM,Keller JJ,Wormhoudt TA,Giardiello FM,Offerhaus GJ,van der Neut R,Pals ST:Sulindac targets nuclear beta-catenin accumulation and wnt signalling in adenomas of patients with familial adenomatous polyposis and in human colorectal cancer cell lines.Br J Cancer 2004:90:224-229.
174 James LF,Panter KE,Gaffield W,Molyneux RJ:Biomedical applications of poisonous plant research.J Agric Food Chem 2004;52:3211-3230.
175 Chen X,Horiuchi A,Kikuchi N,Osada R,YoshidaJ,ShiozawaT,Konishi 1:Hedgehog signal pathway is activated in ovarian carcinomas,correlating with cell proliferation:It's inhibition leads to growth suppression and apoptosis.Cancer Sci 2007;98:68-76.
176 Chen JK,Taipale J,Cooper MK,Beachy PA:Inhibition of hedgehog signaling by direct binding of cyclopamine to smoothened.Genes Dev 2002;16:2743-2748.
177 Yilmaz OH,Valdez R,Theisen BK,Guo W,Ferguson DO,Wu H,Morrison SJ:Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells.Nature 2006;441:475-482.
178 Tsimberidou AM,Giles FJ,Estey E,O'Brien S,Keating MJ,KantarjianHM:The role of gemtuzumab ozogamicin in acute leukaemia therapy.Br J Haematol 2006;132:398-409.
179 Sperr WR,Florian S,Hauswirth AW,Valent P:Cd 33 as a target of therapy in acute myeloid leukemia:Current status and future perspectives.Leuk Lynon-SPhoma2005;46:1115-1120.
180 Moserle L,Indraccolo S,Ghisi M,Frasson C.,Fortunato E,Canevari S,Miotti S,Tosello V.Zamarchi R,Corradin A,Minuzzo S,Rossi E,Basso G,Amadori A:The side population of ovarian cancer cells is a primary target of ifh-alpha antitumor effects.Cancer Res 2008;68:5658-5668.
181 Sarkar FH,Li Y:Using chemopreventive agents to enhance the efficacy of cancer therapy.Cancer Res 2006;66:3347-3350.
182 Sun SY,Hail N,Jr.,Lotan R:Apoptosis as a novel target for cancer chemoprevention.J Natl Cancer Inst 2004;96:662-672.
183 Shay JW,Wright WE:Telomerase:A target for cancer therapeutics.Cancer Cell 2002;2:257-265.
184 Beachy PA.Karhadkar SS.Berman DM:Tissue repair and stem cell renewal in carcinogenesis.Nature 2004;432:324-331.
185 Aggarwal BB,Shishodia S,Sandur SK,Pandey MK,Sethi G:Inflammation and cancer:How hot is the link? Biochem Pharmacol 2006;72:1605-1621.
186 Mimeault M,Batra SK:Recent advances on multiple tumorigenic cascades involved in prostatic cancer progression and targeting therapies.Carcinogenesis 2006;27:1-22.
187 Mimeault M,Batra SK:Concise review:Recent advances on the significance of stem cells in tissue regeneration and cancer therapies.Stem Cells 2006;24:2319-2345.
188 Trosko JE,Tai MH:Adult stem cell theory of the multi-stage,multi-mechanism theory of carcinogenesis:Role of inflammation on the promotion of initiated stem cells.Contrib Microbiol 2006;13:45-65.
189 Arora A,Scholar EM:Role of tyrosine kinase inhibitors in cancer therapy.J Pharmacol Exp Ther 2005;315:971-979.
190 Warrell RP.Jr..de The H,Wang ZY,Degos L:Acute promyelocyte leukemia.N Engl J Med 1993;329:177-189.
191 Piccirillo SG,Reynolds BA,Zanetti N,Lamorte G,Binda E,Broggi G,Brem H,Olivi A, Dimeco F,Vescovi AL:Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells.Nature 2006;444:761-765.
192 Jain M,Arvanitis C,Chu K,Dewey W,Leonhardt E,Trinh M,Sundberg CD,Bishop JM,Felsher DW:Sustained loss of a neoplastic phenotype by brief inactivation of myc.Science 2002;297:102-104.
193 王建伟:人参总皂苷对cd 34+造血干/祖细胞体外扩增和分化的作用及机制研究.重庆,重庆医科大学,2004 pp 61.
194 高月,马增春,谭洪玲:四物汤及其提取物对辐射致血虚证小鼠造血作用的研究.天津中医药2003;20:1.
195 刘丹:同基因骨髓移植小鼠骨髓细胞pecam21(cd31)分子表达与川芎嗪促进造血重建作用的研究.武汉,华中科技大学,2004,pp21.
196 刘晓,武正炎,范萍:黄芪与粒细胞---集落刺激因子对外周血干细胞移植术后早期造血功能重建影响的观察.南京医科大学学报2000;20:4.
197 刘柏炎,蔡光先:补阳还五汤对低糖低氧损伤神经干细胞移行分化的影响.中国药物与临床2005 5:3.
198 孙晋浩,杨琳,高英茂:补阳还五汤对神经干细胞生长分化的影响.山东大学学报(医学版)2002;10:3.
199 张密霞,李越,杜嵘,张艳军:黄岑苷对体外培养神经干细胞分化的影响.天津中医药大学学报 2007;26:3.
200 刘建军,姚忠祥,秦茂林:单味黄芪红花丹参注射对神经干细胞分化影响的初步研究.第三军医大学学报2006;28:3.
201 黎晖,周健洪,陈东风:龟板对大鼠骨髓间充质干细胞向成骨分化的影响.中药新药与临床药理2005;16:3.
202 赛音其木格,娜仁图娅,杨健:大黄素诱导人骨髓间充质干细胞向成骨细胞分化的研究.中国中西医结合外科杂志2006;12:5.
203 杨忠奇,冼绍祥.汪朝晖:三七总皂苷对骨髓间充质干细胞分化为心肌样细胞的作用.中药新药与临床药理2006;17:4.
204 肖鲁伟,武中庆,季卫锋:右归饮诱导胎兔骨髓基质细胞向软骨细胞分化的实验研究.中国中医药科技2005;12:2.
205 姚晓黎,刘卫彬,柳太云:参芪液对成人骨髓间质干细胞的诱导分化作用.中国神经精 神疾病杂志2004;30:2.
206 刘金保,董晓先,董燕湘:多种中药成分诱导大鼠骨髓间质干细胞转变为神经元样细胞.中国药物与临床2003;3:3.
207 余勤,连俊兰,郭莹;丹参注射液诱导大鼠骨髓间充质干细胞分化为神经元样细胞的实验研究.中国中西医结合急救杂志2006;13:4.
208 杨立业,刘相名.惠国桢:丹参诱导鼠骨髓间充质细胞向神经元分化.中华神经外科疾病研究杂志 2003;2:4.
209 撒亚莲,李海标:川芎嗪诱导大鼠骨髓间质干细胞分化为神经元样细胞的研究.解剖学报 2003;34:4.
210 黄慧,唐云安,张成:香丹注射液定向诱导大鼠骨髓间质细胞分化为神经元样细胞.中药材2004;27:4.
211 Nelson WJ,Nusse R:Convergence of wnt,beta-catenin,and cadherin pathways.Science 2004;303:1483-1487.
212 Bienz M:Tcf:Transcriptional activator or repressor? Curr Opin Cell Biol 1998;10:366-372.
213 Loontiens FG,Regenfuss P,Zechel A,Dumortier L,Clegg RM:Binding characteristics of hoechst 33258 with calf thymus DNA,poly[d(a-t)],and d(ccggaattccgg):Multiple stoichiometries and determination of tight binding with a wide spectrum of site affinities.Biochemistry 1990;29:9029-9039.
214 Amdt-Jovin DJ,JovinTM:Analysis and sorting of living cells according to deOMribonucleic acid content.J Histochem Cytochem 1977;25:585-589.
215 Gregoire M,Hernandez-Verdun D,Bouteille M:Visualization of chromatin distribution in living pto cells by hoechst 33342 fluorescent staining.Exp Cell Res 1984;152:38-46.
216 Kim JB,Lee KM,Ko E,Han W,Lee JE,Shin I,Bae JY,Kim S,Noh DY:Berberine inhibits growth of the breast cancer cell lines mcf-7 and mda-mb-231.Planta Med 2008;74:39-42.
217 Zou J,Ran ZH,Xu Q,Xiao SD:Experimental study of the killing effects of OM on human colon cancer cell line sw 1116.Chin J Dig Dis 2005;6:15-20.
218 汤铭新.余桂清,段凤舞:中医扶正培本方药的抗肿瘤实验研究.癌症进展杂志1986
219 中国中医研究院广安门医院胃癌协作组:健牌益肾法对胃肠道癌术后化疗反应的临床及实验观察.河北医药1982
220 李杰,林洪生,孙桂芝:中医药治疗肿瘤研究现状的反思及展望.中医约学刊2005;23:3.
221 唐晓颇,孙桂芝,吴洁:健脾补肾方对胃癌细胞系mgc.803线粒体膜电位和细胞内活性氧的影响.中国实验方剂学杂志 2005;11:4.
222 王宁生,雷燕,刘平:关于血清药理学的思考.中国中西医结合杂志1999;19:1.
223 李军昌,夏天,黄熙:中药复方数理的研究工具.血清药理学.中药药理与临床199814:1.
224 张红敏,谢春光,陈世伟:含药血清体外药理试验的评价.中国中西医结合杂志 200424:1.
225 王建华,张永祥:中药药理与临床研究进展.北京,军事医学科学出版社,2002.
226 蒙一纯,丁霞,贲长恩:中药血清药理学应用研究展望.北京中医药大学学报 1999;22:2.
227 杨秀荣,郝美荣:中药成分代谢分析.中药成分代谢分析.
228 刘成海:中药复方体外药效学研究思考.中药新药与临床药理2000;11:3.
229 张群豪,蓓钟,陈可冀:用血消药理学方法观察血府逐瘀汤浓缩丸对实验性动脉粥样硬化家兔主动脉平滑肌细胞增殖的影响.中国中西医结合杂志1996 16:1.
230 李仪奎:中药血清药理学实验方法的若干问题.中药新约与临床药理1999;10:1.
231 贺玉琢:日本汉方药“血清药理学”、“血清药化学”的研究概况.国外医学·中医中药分册1998;20:1.
232 郑建军,吴新华,张再跃:十全大补汤对肿瘤患者放化疗减毒作用的观察.山东中医杂志 2000;19:1.
233 毛小娟:红芪和黄芪多糖的免疫调节作用.中华微生物和免疫学杂志1998;8:1.
234曾雪渝:香姑胞内糖、胞外糖对正常小鼠免疫功能的影响.中草药1985;16:1.
235 王亚平,祝彼得:当归多糖对造血祖细胞调控机理研究.中华医学杂志1996;76:1.
236 敏郑,王亚平:中药多糖抗肿瘤的药理学研究进展.国外医学·中医中药分册2000;22:1.
237 周金黄:中药现代化主要问题思考.中药药理与临床1998;14:1.
238 浩姜,樊光华.李全忠:人参皂甙激活恶性胸水中的tils及其与吉西他滨协同抗癌作用的实验研究[南华大学学报(医学版2002;30:1.
239 周志文:枸杞子多糖对小鼠骨髓造血干细胞、粒单系祖细胞增殖分化的影响.中药药理学毒理学杂志1991;5:1.
240 Knoblich JA:Mechanisms of asymmetric stem cell division.Cell 2008;132:583-597.
241 Yang L,Wang L,Geiger H,Cancelas JA,Mo J,Zheng Y:Rho gtpase cdc42 coordinates hematopoietic stem cell quiescence and niche interaction in the bone marrow.Proc Natl Acad Sci U S A 2007;104:5091-5096.
242 Ishikawa F,Yoshida S,Saito Y,Hijikata A,Kitamura H,Tanaka S,Nakamura R,Tanaka T,Tomiyama H,Saito N,Fukata M,Miyamoto T,Lyons B,Ohshima K,Uchida N,Taniguchi S,Ohara O,Akashi K,Harada M,Shultz LD:Chemotherapy-resistant human ami stem cells home to and engraft within the bone-marrow endosteal region.Nat Biotechnol 2007;25:1315-1321.
243 Ao M,Franco OE,Park D,Raman D,Williams K,Hayward SW:Cross-talk between paracrine-acting cytokine and chemokine pathways promotes malignancy in benign human prostatic epithelium.Cancer Res 2007;67:4244-4253.
244 Mishra PJ,Humeniuk R,Medina DJ,Alexe G,Mesirov JP,Ganesan S,Glod JW,Banerjee D:,Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells.Cancer Res 2008;68:4331-4339.
245 Karnoub AE,Dash AB,Vo AP,Sullivan A,Brooks MW,Bell GW.Richardson AL,Polyak K,Tubo R,Weinberg RA:Mesenchymal stem cells within tumour stroma promote breast cancer metastasis.Nature 2007;449:557-563.
246 Ramasamy R,Lam EW,Soeiro 1,Tisato V.Bonnet D,Dazzi F:Mesenchymal stem cells inhibit proliferation and apoptosis of tumor cells:Inon-SPact on in vivo tumor growth.Leukemia 2007;21:304-310.
247 Dwyer RM,Potter-Beirne SM,Harrington KA,Lowery AJ,Hennessy E,Murphy JM,Barry FP.O'Brien T,Kerin MJ:Monocyte chemotactic protein-1 secreted by primary breast tumors stimulates migration of mesenchymal stem cells.Clin Cancer Res 2007;13:5020-5027.
248 Ren C.,Kumar S,Chanda D,Kallman L,Chen J,Mountz JD,Ponnazhagan S:Cancer gene therapy using mesenchymal stem cells expressing interferon-beta in a mouse prostate cancer lung metastasis model.Gene Ther 2008;15:1446-1453.
249 Djouad F,Plence P,Bony C.,Tropel P.Apparailly F,Sany J,Noel D,Jorgensen C:Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals.Blood 2003;102:3837-3844.
250 Ning H,Yang F.Jiang M,Hu L,Feng K,Zhang J,Yu Z,Li B? Xu C.,Li Y.Wang J,Hu J,Lou X,Chen H:The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients:Outcome of a pilot clinical study.Leukemia 2008;22:593-599.