凋亡相关基因在放线菌素D诱导胃癌细胞凋亡中的作用及其在胃癌组织中的表达和临床意义
|
摘要
目的：许多抗肿瘤化疗药物虽然结构不同、作用机制不同、作用靶点一不同，但都可能诱导肿瘤细胞的凋亡。本研究通过观察放线菌素D(ActD)对体外培养的胃腺癌BGC823细胞生长增殖、凋亡的影响及表达Survivin、HSP70和Cox-2的变化，探讨ActD与胃腺癌细胞凋亡的关系和ActD诱导细胞凋亡的分子机制。用基因芯片研究放线菌素D诱导胃癌细胞凋亡的相关差异表达的基因。同时检测了胃癌组织中Survivin、Cox-2和HSP-70的表达，探讨三者与胃癌发生发展的可能关系。
方法：应用MTT观察了ActD及其类似物对胃癌BGC-823细胞生长增殖的影响，应用基因芯片、流式细胞仪、激光共聚焦显微镜和电子显微镜等技术检测了ActD对胃癌BGC-823细胞的诱导凋亡作用及差异表达的基因；RT-PCR观察了用药前后胃癌细胞表达Survivin、Cox-2、HSP70等几种凋亡相关基因的变化；构建胃癌组织芯片，应用免疫组织化学方法检测Survivin、Cox-2和HSP-70在胃癌组织中的表达并对三者相关性及临床意义进行初步探讨。
结果：1．浓度大于5.0×10~(-9)mol/l时，ActD对胃腺癌细胞的生存有显著的影响，并呈剂量、时间依赖性，随着药物浓度的增高和作用时间的延长，ActD对体外培养的BGC823细胞的生长抑制作用亦增强，且差异有统计学意义(P＜0.05)。ActD类似物中[D-Phe~2，D-Me-Phe~5]_2 AMD，[D-Phe~2，D-Me-Val~5]_2，与母体对BGC823细胞的生长抑制作用相似，但是两种类似物和母体相比较，对胃腺癌BGC823细胞生长的抑制率在各作用时间内、各浓度组中均略低于母体。
2．浓度为1.0×10~(-7)，5.0×10~(-8)mol/l时，ActD主要以细胞毒作用为主，流式细胞术检测发现其主要表现为坏死峰；浓度为1.0×10~(-8)，5.0×10~(-9)，1.0×10~(-9)mol/l时，ActD作用72h后可诱导BGC823细胞发生凋亡，在G1期前出现明显的凋亡峰，尤以5.0×10~(-9)mol/l最为显著，凋亡率分别为8.0％、28.0％、7.8％；当作用时间小于72h时，仅有5.0×10~(-9)mol/l组出现明显的凋亡峰，凋亡率为6.0％；ActD处理BGC823细胞大于24h(48h、72h)后，G1期含量则较对照组均有不同程度的升高，而G2、S期细胞含量均有不同程度的降低。
3．经ActD(1.0×10~(-8)，5.0×10~(-9)mol/l)处理48h、72h后，胃腺癌细胞发生凋亡，形成凋亡小体。
4．1.0×10~(-9)mol/l、5.0×10~(-9)mol/l两实验组Survivin mRNA相对表达水平较对照组均降低，而且浓度较高组survivin mRNA相对表达水平更低。5.0×10-9mol/l浓度实验组Cox-2和HSP70mRNA相对表达水平均明显低于浓度1.0×10-9mol/l实验组。
5．ActD处理胃癌BGC-823细胞后，基因芯片筛选出差异表达的基因19条，其中16条表达上调，3条表达下调。主要是与DNA修复、免疫、凋亡、细胞增殖、信号转导等多个相关基因的差异表达。
6．Survivin、Cox-2和HSP70在胃癌中的阳性表达率分别为58.6％(58/99)、60.6％(60/99)和61.6％(61/99)，三者阳性表达与胃癌浸润深度相关(P＜0.05)，Cox-2和HSP70阳性表达与淋巴结转移有关(P＜0.05)；Survivin和HSP70在胃癌组织中共表达率为37.4％(37/99)，Survivin和Cox-2在胃癌组织中共表达率为35.4％(35/99)，Cox-2和HSP70在胃癌组织中共表达率为41.4％(41/99)，三项指标在胃癌中的表达无相关性(P＞0.05)；Kaplan-Meier生存曲线显示三项指标阳性表达与胃癌患者的生存率之间差异无统计学意义(P＞0.05)；单因素Cox回归模型分析结果显示，胃癌浸润深度、患者性别、淋巴结转移及Cox-2蛋白表达等四因素与患者预后有关，具有统计学意义(P＜0.05)；多因素Cox回归模型分析结果仅见胃癌浸润深度、胃癌患者性别及淋巴结转移等三因素具有独立的预后意义(P＜0.05)；胃癌多因素Cox回归模型风险函数：
结论：1．高浓度组ActD主要以细胞毒作用对胃腺癌细胞造成直接杀伤致死作用，对胃癌细胞的生长有显著的抑制作用，且具有时间和浓度依赖性；低浓度组ActD抑制胃腺癌细胞的生长、增殖，主要通过诱导胃癌细胞发生凋亡来实现，低浓度组ActD对胃癌细胞生长、增殖的影响与细胞周期有一定关系；低浓度ActD可以使胃癌细胞Survivin、Cox-2和HSP70表达下调，提示Survivin、Cox-2和HSP70表达下调可能共同参与ActD诱导的胃癌细胞凋亡。
2．ActD类似物中[D-Phe~2，D-Me-Phe~5]_2 AMD，[D-Phe~2，D-Me-Val~5]_2 AMD，对BGC823细胞的生长抑制作用与母体相似，但抑制率低于母体，提示还需对ActD的结构改造作进一步研究。
3．ActD可以影响人胃癌BGC823细胞株凋亡等多个相关基因的差异表达。
4．Survivin、Cox-2和HSP70在胃癌中均有过度表达。Survivin过度表达可能主要参与胃癌发生、发展的早期过程；Cox-2和HSP70与胃癌的浸润、转移密切相关；胃癌浸润深度、患者性别、淋巴结转移及Cox-2蛋白表达等因素与患者预后有关，而胃癌浸润深度、患者性别及淋巴结转移具有独立的预后意义。
Objective In order to investigate the effects of Act D on the growth and proliferation of gastric adenocarcinoma cells and apoptosis of gastric adenocarcinoma cells induced by ActD. To study the effect of ActD on Survivin,Cox-2 and HSP70 mRNA expression of gastric adenocarcinoma cells (BGC823), in vitro. To investigate the prevalence and their clinical significance of Survivin,Cox-2 and HSP70 in gastric carcinoma and screen the prognostic factors of gastric carcinoma.
Methods MTT assay was used to observe the viability and growth inhibition of human gastric adenocarcinoma cells (BGC823) after different time treatment with various concentrations of ActD and ActD analogs. The percentage of apoptotic cells and the cell-cycle distribution of BGC823 cells treated with ActD were measured by flow cytometry (FCM). Using the transmission electron microscopy (TEM), the change of ultrastructural organization of BGC823 cells was observed. Expression of Survivin,Cox-2 and HSP70 mRNA was detected using RT-PCR in gastric cancer cells (BGC823).To identify and analysis the differentially expressed genes profile on gastric cancer cells (BGC823) by cDNA microarray.The gastric cancer tissue microarrays (TMA) containing 99 gastric cancer specimens from different clinical stages were used to determine Survivin,Cox-2 and HSP70 expression by immunohistochemistry.
Results 1.When the concentrations of ActD were higher than 5.0×10~(-9)mol/l, the cell growth of BGC823 was suppressed statistically in dose- and time- dependent manner (P<0.05). ActD analogs [D-Phe~2, D-Me-Phe~5]_2 AMD and [D-Phe~2, D-Me-Val~5] AMD_2 were similar with ActD suppressed the cell growth of BGC823.The inhibition ratio of ActD analogs were lower than that ActD.
2.After 48h and 72h treatment with the higher concentrations of ActD (1.0×10~(-7), 5.0×10~(-8)mol/l), the cell growth of BGC823 was suppressed remarkably and necrotic peak was observed in all specimens.The percentage of apoptotic cells increased to 8.0%, 28.0% and 7.8% after 72h treatment with 1.0×10~(-8), 5.0×10~(-9) and 1.0×10~(-9) mol/l of ActD, respectively, and increased to 6.0% after 48h treatment with 5.0×10~(-9)mol/l of ActD, while the percentage of apoptotic cells was unchanged after less than 72h incubation with 1.0×10~(-8) and 1.0×10~(-9)mol/l of ActD.After 24h treatment with 1.0×10~(-8), 5.0×10~(-9) and 1.0×10~(-9)mol/l of ActD, the G1 phase content of BGC823 cells decreased and the G2 phase content of BGC823 cells increased as compared with control group. However, the G1 phase content of BGC823 cells increased and the G2, S phase content of BGC823 cells decreased as compared with control group after 48h and 72h treatment.
3.After 48h and 72h incubation with the higher concentrations of ActD (1.0×10~(-7), 5.0×10~(-8)mol/l,1.0×l0~(-9)mol/l), nuclear condensation, nuclear fragmentation and apoptotic bodies were observed.
4. After 72h treatment with 1.0×10~(-9) and 5.0×10~(-9)mol/l of ActD, the relative expression level of survivin mRNA was down in gastric cancer cells.The relative expression level of Cox-2 and HSP70 mRNA treatmented with 5.0×10~(-9)mol/l was lower obviously it treatmented with 1.0×10~(-9) mol/l.
5. After the gastric cancer cells was treatment with of ActD, 16 genes were up-regulated and 3 genes were down-regulated.The profile of these differentially expressed mainly focus on DNA repair genes,immunologic genes,apoptosis genes,cell proliferation genes,signal transduction genes,etc.
6.The expression rates of Survivin,Cox-2 and HSP70 were 58.6% (58/99),60.6% (60/99) and 61.6%(61/99), respectively. There were a significant correlation between Survivin,Cox-2 and HSP70 expression and the depth of invasion(P<0.05).Cox-2 and HSP70 were found to be statistically associated with lymph node metastasis of gastric cancers (P<0.05). Coexpression rates of survivin and Cox-2 and HSP70 were observed in 37.4%,35/99,41/99,respectively. But no statistically significant correlation was found (P>0.05). Kaplan-Meier survival plots for 89 patients showed no significant relationship(P>0.05) between Survivin,Cox-2 and HSP70 expression and the 5-year survival rates of patients with gastric carcinoma.In the initial univariate analysis of 89 gastric cancer cases followed up, the depth of invasion, sex, lymph node metastasis,Cox-2 expression were all significant(P<0.05). Multiple Cox regression analyses demonstrated that the depth of invasion,sex and lymph node metastasis were independent prognosticators(P<0.05). According to regression coefficients of the depth of invasion,sex and lymph node metastasis in the final Cox regression analysis, a risk function of postoperative patients with gastric cancers was established as follows:h(t)=[h_0(t)]e~(0.411X_1+0.635 X_3+0.630X_6) Conclusions 1. The higher concentrations of ActD cause cell death directly by cytotoxic role and suppress the cell growth of BGC823 notablely in dose- and time- dependent manner. After longer time treatment with the lower concentrations of ActD, the growth and proliferation of gastric adenocarcinoma cells are suppressed significantly due to apoptosis of cells.The lower concentrations of ActD influence the growth of gastric cancer cells by blocking cell cycle. BGC823 cells can be arrested in G2 phase after treatment with the lower concentrations of ActD for shorter time. For longer time, ActD mainly affects G1 phase and arrests cells in G1 phase, i.e, transition from G1 to S phase of gastric cancer cells can be blocked by ActD.The lower concentrations of ActD can cause down-regulated expression of Survivin,Cox-2 and HSP70 mRNA in gastric cancer cells. According to the results of flow cytometry (FCM), transmission electron microscopy (TEM), laser confocal scanning microscopy (LCSM) and RT-PCR, down-regulation of Survivin,Cox-2 and HSP70 mRNA possibly participates in apoptosis of gastric cancer cells induced by ActD.
2. The inhibition ratio of ActD analogs were lower than that ActD.It is necessary that the reforming frame of ActD are studied further.
3. ActD showed significant effecton the differential expression of cells apoptosis genes and other related genes in human gastric carcinoma cells (BGC823).
4.Overexpression of Survivin,Cox-2 and HSP70 are observed in gastric cancers. The upregulated expression of Survivin in gastric carcinoma plays positive role in early stage of human gastric carcinogenesis. Cox-2 and HSP70 may contribute to the growth, the invasion and the lymph node metastasis in gastric carcinoma and display the poor clinical prognosis of patients with gastric carcinoma as an independent prognosticator. The depth of invasion, sex, lymph node metastasis and C0x-2 expression are significant prognostic factors. However, only the depth of invasion, sex and lymph node metastasis can indicate prognosis of patients with gastric carcinoma independently.
方法：应用MTT观察了ActD及其类似物对胃癌BGC-823细胞生长增殖的影响，应用基因芯片、流式细胞仪、激光共聚焦显微镜和电子显微镜等技术检测了ActD对胃癌BGC-823细胞的诱导凋亡作用及差异表达的基因；RT-PCR观察了用药前后胃癌细胞表达Survivin、Cox-2、HSP70等几种凋亡相关基因的变化；构建胃癌组织芯片，应用免疫组织化学方法检测Survivin、Cox-2和HSP-70在胃癌组织中的表达并对三者相关性及临床意义进行初步探讨。
结果：1．浓度大于5.0×10~(-9)mol/l时，ActD对胃腺癌细胞的生存有显著的影响，并呈剂量、时间依赖性，随着药物浓度的增高和作用时间的延长，ActD对体外培养的BGC823细胞的生长抑制作用亦增强，且差异有统计学意义(P＜0.05)。ActD类似物中[D-Phe~2，D-Me-Phe~5]_2 AMD，[D-Phe~2，D-Me-Val~5]_2，与母体对BGC823细胞的生长抑制作用相似，但是两种类似物和母体相比较，对胃腺癌BGC823细胞生长的抑制率在各作用时间内、各浓度组中均略低于母体。
2．浓度为1.0×10~(-7)，5.0×10~(-8)mol/l时，ActD主要以细胞毒作用为主，流式细胞术检测发现其主要表现为坏死峰；浓度为1.0×10~(-8)，5.0×10~(-9)，1.0×10~(-9)mol/l时，ActD作用72h后可诱导BGC823细胞发生凋亡，在G1期前出现明显的凋亡峰，尤以5.0×10~(-9)mol/l最为显著，凋亡率分别为8.0％、28.0％、7.8％；当作用时间小于72h时，仅有5.0×10~(-9)mol/l组出现明显的凋亡峰，凋亡率为6.0％；ActD处理BGC823细胞大于24h(48h、72h)后，G1期含量则较对照组均有不同程度的升高，而G2、S期细胞含量均有不同程度的降低。
3．经ActD(1.0×10~(-8)，5.0×10~(-9)mol/l)处理48h、72h后，胃腺癌细胞发生凋亡，形成凋亡小体。
4．1.0×10~(-9)mol/l、5.0×10~(-9)mol/l两实验组Survivin mRNA相对表达水平较对照组均降低，而且浓度较高组survivin mRNA相对表达水平更低。5.0×10-9mol/l浓度实验组Cox-2和HSP70mRNA相对表达水平均明显低于浓度1.0×10-9mol/l实验组。
5．ActD处理胃癌BGC-823细胞后，基因芯片筛选出差异表达的基因19条，其中16条表达上调，3条表达下调。主要是与DNA修复、免疫、凋亡、细胞增殖、信号转导等多个相关基因的差异表达。
6．Survivin、Cox-2和HSP70在胃癌中的阳性表达率分别为58.6％(58/99)、60.6％(60/99)和61.6％(61/99)，三者阳性表达与胃癌浸润深度相关(P＜0.05)，Cox-2和HSP70阳性表达与淋巴结转移有关(P＜0.05)；Survivin和HSP70在胃癌组织中共表达率为37.4％(37/99)，Survivin和Cox-2在胃癌组织中共表达率为35.4％(35/99)，Cox-2和HSP70在胃癌组织中共表达率为41.4％(41/99)，三项指标在胃癌中的表达无相关性(P＞0.05)；Kaplan-Meier生存曲线显示三项指标阳性表达与胃癌患者的生存率之间差异无统计学意义(P＞0.05)；单因素Cox回归模型分析结果显示，胃癌浸润深度、患者性别、淋巴结转移及Cox-2蛋白表达等四因素与患者预后有关，具有统计学意义(P＜0.05)；多因素Cox回归模型分析结果仅见胃癌浸润深度、胃癌患者性别及淋巴结转移等三因素具有独立的预后意义(P＜0.05)；胃癌多因素Cox回归模型风险函数：
结论：1．高浓度组ActD主要以细胞毒作用对胃腺癌细胞造成直接杀伤致死作用，对胃癌细胞的生长有显著的抑制作用，且具有时间和浓度依赖性；低浓度组ActD抑制胃腺癌细胞的生长、增殖，主要通过诱导胃癌细胞发生凋亡来实现，低浓度组ActD对胃癌细胞生长、增殖的影响与细胞周期有一定关系；低浓度ActD可以使胃癌细胞Survivin、Cox-2和HSP70表达下调，提示Survivin、Cox-2和HSP70表达下调可能共同参与ActD诱导的胃癌细胞凋亡。
2．ActD类似物中[D-Phe~2，D-Me-Phe~5]_2 AMD，[D-Phe~2，D-Me-Val~5]_2 AMD，对BGC823细胞的生长抑制作用与母体相似，但抑制率低于母体，提示还需对ActD的结构改造作进一步研究。
3．ActD可以影响人胃癌BGC823细胞株凋亡等多个相关基因的差异表达。
4．Survivin、Cox-2和HSP70在胃癌中均有过度表达。Survivin过度表达可能主要参与胃癌发生、发展的早期过程；Cox-2和HSP70与胃癌的浸润、转移密切相关；胃癌浸润深度、患者性别、淋巴结转移及Cox-2蛋白表达等因素与患者预后有关，而胃癌浸润深度、患者性别及淋巴结转移具有独立的预后意义。
Objective In order to investigate the effects of Act D on the growth and proliferation of gastric adenocarcinoma cells and apoptosis of gastric adenocarcinoma cells induced by ActD. To study the effect of ActD on Survivin,Cox-2 and HSP70 mRNA expression of gastric adenocarcinoma cells (BGC823), in vitro. To investigate the prevalence and their clinical significance of Survivin,Cox-2 and HSP70 in gastric carcinoma and screen the prognostic factors of gastric carcinoma.
Methods MTT assay was used to observe the viability and growth inhibition of human gastric adenocarcinoma cells (BGC823) after different time treatment with various concentrations of ActD and ActD analogs. The percentage of apoptotic cells and the cell-cycle distribution of BGC823 cells treated with ActD were measured by flow cytometry (FCM). Using the transmission electron microscopy (TEM), the change of ultrastructural organization of BGC823 cells was observed. Expression of Survivin,Cox-2 and HSP70 mRNA was detected using RT-PCR in gastric cancer cells (BGC823).To identify and analysis the differentially expressed genes profile on gastric cancer cells (BGC823) by cDNA microarray.The gastric cancer tissue microarrays (TMA) containing 99 gastric cancer specimens from different clinical stages were used to determine Survivin,Cox-2 and HSP70 expression by immunohistochemistry.
Results 1.When the concentrations of ActD were higher than 5.0×10~(-9)mol/l, the cell growth of BGC823 was suppressed statistically in dose- and time- dependent manner (P<0.05). ActD analogs [D-Phe~2, D-Me-Phe~5]_2 AMD and [D-Phe~2, D-Me-Val~5] AMD_2 were similar with ActD suppressed the cell growth of BGC823.The inhibition ratio of ActD analogs were lower than that ActD.
2.After 48h and 72h treatment with the higher concentrations of ActD (1.0×10~(-7), 5.0×10~(-8)mol/l), the cell growth of BGC823 was suppressed remarkably and necrotic peak was observed in all specimens.The percentage of apoptotic cells increased to 8.0%, 28.0% and 7.8% after 72h treatment with 1.0×10~(-8), 5.0×10~(-9) and 1.0×10~(-9) mol/l of ActD, respectively, and increased to 6.0% after 48h treatment with 5.0×10~(-9)mol/l of ActD, while the percentage of apoptotic cells was unchanged after less than 72h incubation with 1.0×10~(-8) and 1.0×10~(-9)mol/l of ActD.After 24h treatment with 1.0×10~(-8), 5.0×10~(-9) and 1.0×10~(-9)mol/l of ActD, the G1 phase content of BGC823 cells decreased and the G2 phase content of BGC823 cells increased as compared with control group. However, the G1 phase content of BGC823 cells increased and the G2, S phase content of BGC823 cells decreased as compared with control group after 48h and 72h treatment.
3.After 48h and 72h incubation with the higher concentrations of ActD (1.0×10~(-7), 5.0×10~(-8)mol/l,1.0×l0~(-9)mol/l), nuclear condensation, nuclear fragmentation and apoptotic bodies were observed.
4. After 72h treatment with 1.0×10~(-9) and 5.0×10~(-9)mol/l of ActD, the relative expression level of survivin mRNA was down in gastric cancer cells.The relative expression level of Cox-2 and HSP70 mRNA treatmented with 5.0×10~(-9)mol/l was lower obviously it treatmented with 1.0×10~(-9) mol/l.
5. After the gastric cancer cells was treatment with of ActD, 16 genes were up-regulated and 3 genes were down-regulated.The profile of these differentially expressed mainly focus on DNA repair genes,immunologic genes,apoptosis genes,cell proliferation genes,signal transduction genes,etc.
6.The expression rates of Survivin,Cox-2 and HSP70 were 58.6% (58/99),60.6% (60/99) and 61.6%(61/99), respectively. There were a significant correlation between Survivin,Cox-2 and HSP70 expression and the depth of invasion(P<0.05).Cox-2 and HSP70 were found to be statistically associated with lymph node metastasis of gastric cancers (P<0.05). Coexpression rates of survivin and Cox-2 and HSP70 were observed in 37.4%,35/99,41/99,respectively. But no statistically significant correlation was found (P>0.05). Kaplan-Meier survival plots for 89 patients showed no significant relationship(P>0.05) between Survivin,Cox-2 and HSP70 expression and the 5-year survival rates of patients with gastric carcinoma.In the initial univariate analysis of 89 gastric cancer cases followed up, the depth of invasion, sex, lymph node metastasis,Cox-2 expression were all significant(P<0.05). Multiple Cox regression analyses demonstrated that the depth of invasion,sex and lymph node metastasis were independent prognosticators(P<0.05). According to regression coefficients of the depth of invasion,sex and lymph node metastasis in the final Cox regression analysis, a risk function of postoperative patients with gastric cancers was established as follows:h(t)=[h_0(t)]e~(0.411X_1+0.635 X_3+0.630X_6) Conclusions 1. The higher concentrations of ActD cause cell death directly by cytotoxic role and suppress the cell growth of BGC823 notablely in dose- and time- dependent manner. After longer time treatment with the lower concentrations of ActD, the growth and proliferation of gastric adenocarcinoma cells are suppressed significantly due to apoptosis of cells.The lower concentrations of ActD influence the growth of gastric cancer cells by blocking cell cycle. BGC823 cells can be arrested in G2 phase after treatment with the lower concentrations of ActD for shorter time. For longer time, ActD mainly affects G1 phase and arrests cells in G1 phase, i.e, transition from G1 to S phase of gastric cancer cells can be blocked by ActD.The lower concentrations of ActD can cause down-regulated expression of Survivin,Cox-2 and HSP70 mRNA in gastric cancer cells. According to the results of flow cytometry (FCM), transmission electron microscopy (TEM), laser confocal scanning microscopy (LCSM) and RT-PCR, down-regulation of Survivin,Cox-2 and HSP70 mRNA possibly participates in apoptosis of gastric cancer cells induced by ActD.
2. The inhibition ratio of ActD analogs were lower than that ActD.It is necessary that the reforming frame of ActD are studied further.
3. ActD showed significant effecton the differential expression of cells apoptosis genes and other related genes in human gastric carcinoma cells (BGC823).
4.Overexpression of Survivin,Cox-2 and HSP70 are observed in gastric cancers. The upregulated expression of Survivin in gastric carcinoma plays positive role in early stage of human gastric carcinogenesis. Cox-2 and HSP70 may contribute to the growth, the invasion and the lymph node metastasis in gastric carcinoma and display the poor clinical prognosis of patients with gastric carcinoma as an independent prognosticator. The depth of invasion, sex, lymph node metastasis and C0x-2 expression are significant prognostic factors. However, only the depth of invasion, sex and lymph node metastasis can indicate prognosis of patients with gastric carcinoma independently.
引文
1. Kerr JFR,Wyllie AH,Currie AR.Apoptosis:a basic biological phenomenon with wide-rangeing implication in tissue kenetics.Br J Cancer. 1972,26(4):239-257.
2. Vaux DL, Korsmeyer SJ.Cell death in development. Cell,1999,96(2):245-254.
3. Mahotka C,Wenzel M,Springer E,et al. Survivin-deltaEx3 and survivin-2B: two novel splice variants of the apoptosis inhibitor Survivin with different antiapoptotic properties. Cancer Res,1999,59(24):6097-6102.
4. He J,Agarwal ML,Larkin HE,et al.The induction of partial resistance to photodynamic therapy by the protooncogene BCL-2.Photochenl Photobiol,1996,64(5):845-852.
5. Kamesaki S,Kamesaki H,Jorgensen TJ,et al.bcl-2 protein inhibits etoposide-induced apoptosis through its effects on events subsequent to topoisomerase- II induced DNA strand breaks and their repair.Cancer Res,1993,53:4251-4256.
6. Shimizu S,Eguchi Y.Kosada H,et al.Prevention of hypoxia-induced cell death by Bcl-2 and Bcl-xl.Nature,1995,374(6525):811-813.
7. Wang H.Combined effect of docetaxel and cisplatin for non-small cell lung cancer cell lines in vitro.Nagoya J Med Sci,2000,63(3-4):129-137.
8. Takahashi Y,Nagata T,Ishii Y,et al.Up-regulation of vitamin D3 up-regulated protein 1 gene in response to 5-fluorouracil in colon carcinoma SW620.Oncol Rep,2002, 9(1):75-79.
9. Seewaldt VL,Mrozek K , Dietze EC,et al.Human papillomavirus type 16E6 inactivation of p53 in normal human mammary epithelial cells promootes tamoxifen-mediated apoptosis.Cancer Res,2001,61(2):616-624.
10. Chu W.Pak BJ,Bani MR,et al.Tyrosinase-related protein 2 as a mediator of melanoma specific resistance to cis-diamminedichloroplatinum( II): therapeutic implications. Oncogene,2000,19(3):395-402.
11. Miyake H,Hara S,Arakawa S,et al.Optimal timing and dosage of chemotherapy as a combined treatment with androgen withdrawal in the human prostate LNCaP tumour model.Br J Cancer,2001,84(6):859-863.
12. Buckley AR.Lessons from anticancer research might provide new insights into mechanisms of hormone action.Trends Endocrinol Metab,2001,12(3):87-89.
13. Fulda S,Susin SA,Kromer G,et al.Molecular ordering of apoptosis induced by anticancer drugs in neuroblastoma cells.Cancer Res,1998,58:4453-4460.
14. Duque G,Elabdaimi K,Henderson JE,et al.Vitamin D inhibits Fas ligand induced apoptosis in human osteoblasts by regulating components of both the mitochondrial and Fas related pathways.Bone,2004,35(1):57-64.
15. Wagner N,Wagner KD,Schley G,et al.l,25-dihydroxyvitaminD3-indrced aoptosis of retinoblastoma cells is associated with reciprocal changes of bcl-2 and bax.Exp Eye Res,2003,77(1):1-9.
16. Brenner C, Kroemer G. Mitochondria:the death signal integrators. Science, 2000, 289(5482):1150-1151.
17. Liu X,Kim CN,Yang J,et al.Induction of apoptosis program in cell-free extracts: requirement for dATP and cytochrome C.Cell,1996,86(1):147-157.
18. Jiang X,Wang X.Cytochrome c promotes caspase-9 activation by inducing nucleotide binding to Apaf-1.J Biol Chem,2000,275:31199-31203.
19. Lum JJ, Bbawor DE,Kong M,et al.Growth factor regulation of autophage and cell survival in the absence of apoptosis.Cell,2005,120(2):237-248.
20. Ruled SJ,Renatus M,Schwarzenbacher R,et al.Structural basis for the inhibition of caspase 3 by XIAP.Cell,2001,104(5):791-800.
21. Suzuki Y,Nakabayashi Y,Takahashi R.Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effcet in Fas-induced cell death.Proc Natl Acad Sci USA,2001,98(15):8662-8667.
22. Du C,Fang M,Li Y,et al.Smac,a mitochondnal protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition.Cell,2000,102(1):33-42.
23. Srinivasula SM,Hegde R,Saleh A,et al.A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis.Nature,2001, 410(6824):112-116.
24. Chai J,Du C,Wu JW,et al.Structural and biochemical basis of apoptotic activation by Smac/DIABLO.Nature,2000,406(6798):855-862.
25. Liu ZH,Sun C,Olejniczak ET,et al.Structural basis for binding of Smac DIABLO to the XIAP BIR3 domain.Nature,2000,408(6815):1004-1008.
26. Miramar MD,Costantini P,Ravagnan L,et al.NADH oxidase activity of mitochondrial apoptosis-inducing factor.J Biol Chem,2001,276(19): 16391-16398.
27. Susin SA,Lorenzo Hk,Zamzami N,et al.Molecular characterization of mitochondrial apoptosis-inducing factor.Nature,1999,397(6718):441-446.
28. Woo RA,Melure KG, Lees-Miller SP,et al.DNA-dependent protein kinase acts upstream of p53 in response to DNA damage.Nature,1998,394(6694):700-704.
29. Kim R,Ohi Y,Inoue H,et al.Enhancement of chemotherapeutic agents induced-apoptosis associated with activation of c-Jun N-terminal kinase 1 and caspase 3 (CPP32) in bax-transfected gastric cancer cells.Anticancer Res,2000,20(1A):439-444.
30. Wright SC,Wang H,Wei QS,et al.Bcl-2 mediated resistance to apoptosis is associated with glutathione-induced inhibition of Ap24 activation of nuclear DNA fragmentation. Cancer Res,1998,58(23):5570-5576.
31. Sim BKL, MacDonald NJ, Edward RG Angiostatin and endostatin: endogenous inhibitors of tumor growth.Cancer Metastasis Rev,2000,19(l,2):181-190.
32. Eskens F.Angiogenesis inhibitors in clinical development:where are we now and where are we going?Br J Cancer, 2004,90(1): 1-7.
33. Li C,Thompson CB.DNA damage,deamidation,and death.Science,2002,298 (5597): 1346-13467.
34. Pozniak CD,Radinovic S,Yang A,et al.An anti-apoptotic role for the p53 family member, p73,dufing developmental neuron death. Science,2000,289 (5477):304-306.
35. Fulda S,Meyer E, Friesen C,et al.Cell type specific involvement of death receptor and mitochondfial pathways in drug-induced apootosis.Oncogene,2001,20(9):1063-1075.
36. Timmer T, Vries EGE,Jong S.Fas receptor mediated apoptosis:a clinical application.Pathol,2002,196(2): 125-134.
37. Wajant H.The Fas signaling pathway:more than a paradigm.Science,2002,296(5573): 1635-1636.
38．任含平，施广霞．FAS信号转导与其抑制机．国外医学生理、病理科学与临床分册,2004,24(4)：329-330．
39. Kaufmann SH,Earnshaw WC.Induction of apoptosis by cancer chemotherapy.Exp Cell Res,2000,256(1):42-49.
40. Pimentel-Muinos FX,Seed B.Regulated commitment of TNF receptor signaling:a molecular switch for death or activation.Immunity,1999,11(6):783-793.
41. Wang T, Zhang X,Li JJ.The role of NF-kappaB in the regulation of cell stress responses.Tnt Immunopharmacol,2002,2(11): 1509-1520.
42. Wiley SR,Schoole YK, Smolak PJ,et al.Identification and characterization of a new member of the TNF family that induces apoptosis.Immunity,1995,3(6):673-682.
43．张军，马远方，赵粤萍，等．死亡受体 5 在肝癌细胞系及肝细胞系表面的表达．中国肿瘤临床,2006,33(5)：287-289．
44. Kaise N, Edelman IS. Calcium dependence of glueocorticoid-induced lymphocytolysis.Proc Natl Acad Sci USA.1977,74(29):638-642.
45. Yamagachi T, Chaltopadhyay N,Brown EM.G protein-coupled extra-cellular Ca~(2+) (Cao~(2+))-sensing receptor(CaR):Roles in cell signaling and control of diverse cellular functions.Adv Pharmacol,2000,47:209-213.
46．郭静，蒲咏梅，张东才．钙离子信号与细胞凋亡．生物物理学报,2005,21(1)：1-18．
47. McConkey DJ,Orrenius S.The role of calcium in the regulation of apoptosis.Biochem Biophys Res Commu,1997,239(2):357-366.
48. Wang E,Lee MD,Dunn KW.Lysosomal accumulation of drugs in drug-sensitive MES-SA but not multidrug-resistant MES-SA/Dx5 uterine sarcoma cells.J Cell Physiol, 2000;184(2):263-274.
49. Barry MA,Reynolds JE,Eastman A.Etoposide indued apoptosis in human HL-60 cells is associated with intracellular acidification.Cancer Res,1993,53(10):2349-2357.
50. Gottlieb RA.Apoptosis induced in Jurkat cells by several agents is preced by intracellular acidification.Proc Natl Acad Sci USA,1996,93(2):654-658.
51.Ashkenazi A,Dixit VM. Death receptors: signaling and modulation. Science, 1998, 281(5381):1305-1308.
52. Evan G,Iittlewood T. A matter of life and cell death.Science,1998,281(5381): 1317-1322.
53. LaCasse EC,Baird S,Korneluk RG,et al.The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene,1998,17(25):3247-3259.
54. Mosser DD,Caron AW,Bourget L,et al.Role of human heat shock protein hsp70 in protection against stress-induced apoptosis. Mol Cell Biol,1997,17(9):5317-5327.
55. Ebert MPA,Schafer C, Chen J,et al. Protective role of heat shock protein 27 in gastric mucosal injury.J patholo,2005,207(2): 177-184.
56. Yeo M,Kim DK,Kim YB,et al.Selective Induction of Apoptosis with Proton Pump Inhibitor in Gastric Cancer Cells.Clin Cancer Res,2004,10:8687-8696.
57. Deveraux QL,Reed JC. LAP family proteins-suppressors of apoptosis.Gene Dev, 1999.13(3):239-252.
58. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, Survivin, expressed in cancer and lymphoma. Nat Med,1997,3(8):917-921.
59. Rohayem J,Diestelkoetter P,Weigle B,et al.Antibody response to the tumor associated inhibition of apoptosis protein Survivin cancer patients.Cancer Res,2000,60(7):1815-1817.
60. Bao R, Connolly DC, Murphy M,et al. Activation of cancer-specific gene expression by the Survivin promoter. J Natl Cancer Inst,2002,94(7):522-528.
61. Suzuki A, Ito T, Kawano H, et al.Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death. Oncogene,2000,19(10):1346-1353.
62. Verdecia MA, Huang Hk, Dutil E.et al.Structure of the human anti-apoptotic protein Survivin reveals a dimeric arrangement.Nature Structura Biology,2000,7(7):602-608.
63. Tamm I,Wang Y.Sausville E,et al.IAP family protein Survivin inhibits caspase activity and apoptosis induced by Fas(CD95),Bax,caspases,and anticancer drugs.Cancer Res, 1998,58(23):5315-5320.
64. Ikeguchi M,Ueda T,Sakatani T,et al.Expression of Survivin messenger RNA correlates with poor progenosis patients with hepatocellular carcinoma.Diagn Mol Pathol, 2002,ll(1):33-40.
65. Velculescu VE,Madden SL,Zhang L,et al.Analysis of human transcriptomes.Nat Genet, 1999,23(4):387-388.
66. Yamamoto T.Tanidewa N.The role of Survivin as a new target of diagnosis and treatment in human cancer.Med Electron Microsc,2001,34(4):207-212.
67. Fuller KJ,Issels RD,Slosman DO,et al.Cancer and the heatshock response.Eur J Cancer, 1994,30A(12):1884-1891.
68. Helmbrecht K, Zeise E, Rensing L. Chaperones in cell cycle regulation and mitogenic signal transduction: a review.Cell Prolif,2000,33(6):341-365.
69. Jolly C, Morimoto RI. Role of the heat shock response and molecular chaperones in oncogenesis and cell death.J Natl Cancer Inst,2000,92(19): 1564-1572.
70. Ellis RJ.Molecular chaperones:plugging the transportgap.Nature,2003,421(6925):801-802.
71. Papp E, Nardai G, Soti C, Csermely P. Molecular chaperones, stress proteins and redox homeostasis.Bio factors 2003,17:249-257.
72. Zhang SHL,Wei SO,Li ST.Immunohistochemical study of heatshock protein 70 in mouse endometrium during carly regnancy.J Anat,2002,25(1):21-24.
73. Smith WL,Garavito RM, DeWitt DL. Prostaglandin endoperoxide H synthases (cyclooxygenase)-l and -2. J Biol Chem.1996,271:33157-33160.
74. Chen WS,Wei SJ,Liu JM,et al.Tumor invasiveness and liver metastasis of colon cancer cell correlated with cyclooxygenase-2(COX-2) expression and inhibited by a COX-2-seletive inhibitor,etodolac.Int J Cancer,2001,91(6):894-899.
75. Ratnasinghe D,Tangrea JA,Roth MJ,et al.Expression of the cyclo-oxygenase-2 in human adenocarcinomas of the gastric cardia and corpus.Oncol Rep,1999,6:965-968.
76. Tucker ON, Dannenberg AJ,Yang EK,et al. Cyclo-oxygenase-2 expression is up-regulated in human pancreatic cancer. Cancer Res, 1999,59:987-990.
77. Uefuji K, Ichikura T, Mochizuki H,et al. Expression of cyclooxygenase2 in human gastric adenomas and adenocarcinomas.Surg Oncol,2001,76(1):26-30.
78. Fujita T, Matsui M, Takaku K, et al. Size and invasion dependent increase in cyclo-oxygenase-2 levels in human colorectal carcinomas.Cancer Res, 1998, 58(21):4823-4826.
79. Kawabe A, Shimade Y, Uchida.et al. Expression of cyclooxygenase-2 in primary and remnant gastric carcinoma.Surg Oncol, 2002,80(2):79-88.
80. Wyllie AH, Morris RG, Smith AL, et al. Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol,1984,142(1):67-77.
81. Ratan RR, Murphy TH, Baraban JM. Oxidative stress induces apoptosis in embryonic cortical neurons. J Neurochem,1994,62(1):376-379.
82. Schwartz LM, Kosz L, Kay BK. Gene activation is required for developmentally programmed cell death. Proc Natl Acad Sci USA,1990,87(17):6594-6598.
83. Martin SJ. Protein or RNA synthesis inhibition induces apoptosis of mature human CD4+ Tcell blasts. Immunol Lett,1993,35(2):125-134.
84. Moule AJ, Young WG, Adkins KF. Early cellular events in an actinomycin D-created dentin niche in the rat incisor. J Oral Pathol Med,1993,22(4):159-167.
85. Pagliacci MC, Migliorati G, Smacchia M, et al. Cellular stress and glucocorticoid hormones protect 1929 mouse fibroblasts from tumor necrosis factor alpha cytotoxicity. J Endocrinol Invest,1993,16(8):591-599.
86. Waring P. DNA fragmentation induced in macrophages by gliotoxin does not require protein synthesis and is preceded by raised inositol triphosphate levels. J Biol Chem, 1990,265(24):14476-14480.
87. Borner MM, Myers CE, Sartor O, et al. Drug-induced apoptosis is not necessarily dependent on macromolecular synthesis or proliferation in the p53-negative human prostate cancer cell line PC-3. Cancer Res,1995,55(10):2122-2128.
88. Vaux DL. Toward an understanding of the molecular mechanisms of physiological cell death. Proc Natl Acad Sci USA,1993,90(3):786-789.
89. Martin SJ.Apoptosis:suicide,execution or murder? Trends Cell Biol, 1993,3(5): 141-144.
90. Fernandes RS, Cotter TG. Activation of a calcium magnesium independent endonuclease in human leukemic cell apoptosis.Anticancer Res,1993,13(5A): 1253-1259.
91. Olsson A, Diaz T, Aguilar-Santelises M,et al. Sensitization to TRAIL-induced apoptosis and modulation of FLICE-inhibitory protein in B chronic lymphocytic leukemia by actinomycin D. Leukemia,2001,15(12):1868-1877.
1. Nicholson DW, Thornberry NA.Apoptosis life and death decision. Science. 2003, 299(5604): 214-215.
2. Evan G, Littlewood T.A matter of life and cell death.Science, 1998,281(5381): 1317-1322.
3. Nicholson DW.From bench to clinic with apoptosis-based therapeutic agents. Nature, 2000,407(6805):810-816.
4. Green DR,Evan GI.Amatter of life and death.Cancer Cell,2002,1(1):19-30.
5. Ferber D.Cancer research.A new way to combat therapy side effects.Science, 1999, 285(5434): 1651-1653.
6. Kiechle FL, Zhang X.Apoptosis:biochemical aspects and clinical implications. Clin Chim Acta,2002,326(1-2):27-45.
7. Wang H.Combined effect of docetaxel and cisplatin for non-small cell lung cancer cell lines in vitro.Nagoya J Med Sci,2000,63(3-4):129-137.
8. Okada E,Murai Y, Matsui K, et al. Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients. Cancer Lett, 2001,163(1):109-116.
9. Mahotka C,Wenzel M,Springer E,et al.Survivin-deltaEx3 and survivin-2B:two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties.Cancer Res,1999,59(24):6097-6102.
10. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, Survivin, expressed in cancer and lymphoma. Nat Med,1997,3(8):917-921.
11. Deveraux QL, Reed JC.IAP family proteins-suppressors of apoptosis.J Genes Dev,1999, 13(3):239-252.
12. Shin S, Sung BJ, Cho YS, et al. An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and-7. Biochemistry, 2001,40(4):1117-1123.
13. Tamm I, Wang Y, Sausville E, et al. IAP-family protein Survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res,1998,58(23):5315-5320.
14. Kato J, Kuwabara Y, Mitani M, et al. Expression of Survivin in esophageal cancer: correlation with the prognosis and response to chemotherapy. Int J Cancer,2001,95 (2): 92-95.
15. Wakana Y, Kasuya K, Katayanagi S, et al. Effect of Survivin on cell proliferation and apoptosis in gastric cancer. Oncol Rep, 2002,9(6):1213-1218.
16. Fornaro M, Plescia J, Chheang S, et al. Fibronectin protects prostate cancer cells from tumor necrosis factor-alpha-induced apoptosis via the AKT/survivin pathway. J Biol Chem,2003,278(50):50402-50411.
17. Tanaka K, Iwamoto S, Gon G, et al. Expression of Survivin and its relationship to loss of apoptosis in breast carcinomas.Clin Cancer Res,2000,6(1):127-134.
18. Ikehara M, Oshita F, Kameda Y, et al. Expression of Survivin correlated with vessel invasion is a marker of poor prognosis in small adenocarcinoma of the lung. Oncol Rep,2002,9(4):835-838.
19. Kawasaki H, Altier DC, Lu CD, et al. Inhibition of apoptosis by Survivin predicts shorter survival rates in colorectal cancer. Cancer Res, 1998,58(22):5071-5074.
20. Thompson CB. Apoptosis in the pathogenesis and treatment of disease. J Science, 1995, 267(5203):1456-1462.
21. Ambrosini G, Adida C, Sirugo G, et al. Induction of apoptosis and inhibition of cell proliferation by Survivin gene targeting.J Biol Chem,1998,273(18):11177-11182.
22. Grossman D,Kim PJ,Schechner JS,et al.Inhibition of melanoma tumor growth in vivo by Survivin targeting. Proc Natl Acad Sci USA,2001,98(2):635-640.
23. Appleby SB,Rrstimaki A,Neilson K,et al.Structure of the human cyclo-oxygenase-2 gene.Biochem,1994,302(3):723-727.
24. Chen WS,Wei SJ,Liu JM,et al.Tumor invasiveness and liver metastasis of colon cancer cell correlated with cyclooxygenase-2(COX-2) expression and inhibited by a COX-2 seletive inhibitor,etodolac.Clin Cancer Res,2001,7(4):861-867.
25. Jodj T,Heese O,Nikas DC,et al.Expression of cyclooxygenase 2(COX-2) in human glioma and in vitro ingibition by a specific COX-2 inhibitor-NS-398.Cancer Res,2000, 60(17):4926-4931.
26. Tsujii M,Dubis RN.Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin eneoperoxide synthase 2.Cell,1995,83(3):493-501.
27. Sheng H,Shao J,Morrow JD,et al.Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells.Cancer Res,1998,58(2):362-366.
28. Higashi Y,Kanekura T.Kanzaki T.Enhanced expression of cyclooxygenase (COX-2) in human skin epidermal cancer cells:evidence for growth suppression by inhibiting COX-2 expression.Int J Cancer,2000,86(5):667-671.
29. Ma JH.Sui YF,Ye J,et al.Heat shock protein70/MAGE-3 fusion protein vaccinecan enhance cellular and humoral immune responses to MAGE-3 in vivo.Cancer Immunol Immunother,2005,54(9):907-914.
30. Nei TSZ,QiaoY,QianYWL. The role of heat shock protein in human breast cancer. J Chin Pathology,1998,17(1):34-38.
31. Wang XP,Liu GZ,Song AL,et al.Expression and significance of heat shock protein 70 and glucose-regulated protein 94 in human esophageal carcinoma.World J Gastroenterol,2005,11(3):429-432.
32. Isomoto H,Oka M,YanoY,et al.Expression of heat shock protein (Hsp)70 and Hsp40 in gastric cancer.Cancer Lett,2003,198(2):219-228.
33. Novoselov SS,Verbova MV,Vasileva EV,et al.Expression of Hsp70 and Hdjl chaperone proteins in human tumor cells.Vopr Onkol,2004,50(2):174-178.
34. Volm M,Koomagi R,Mattern J,et al.Protein expression profile of primary human squamous cell lung carcinomas indicative of the incidence of metastases.Clin Exp Metastasis,2002,19(5):385-390.
35．倪京满，杨小武，潘鑫复．抗癌药物放线菌素D及其新类似物体外DNA结合特性研究．兰州大学学报(自然科学版)，2002，38(3)：87-89．
36. Goldberg IH,Friedman PA.Antibiotics and nucleic acids. Annu Rev Biochem, 1971, 40:775-810.
37. Kiechle FL, Zhang X.Apoptosis:biochemical aspects and clinical implications.Clin Chim Acta,2002,326:27-45.
38. Chang TC,Tsai LC,Hung MW, et al.Effects of transcription and translation inhibitors on a human gastric carcinoma cell line. Potential role of Bcl-X(S) in apoptosis triggered by these inhibitors.Biochem Pharmacol.1997,53(7):969-977.
39. Ng CP, Bonavida B.X-linked inhibitor of apoptosis (XIAP) blocks Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis of prostate cancer cells in the presence of mitochondfial activation: sensitization by overexpression of second mitochondria-derived activator of caspase/direct lAP-binding protein with low pl(Smac/DIABLO). Mol Cancer Ther, 2002,1(12):1051-1058.
40. Rudin CM, Thompson CB. Apoptosis and disease: regulation and clinical relevance of programmed cell death. Annu Rev Med,1997,48:267-281.
41. Krieg A, Mahotka C, Krieg T, et al. Expression of different survivin variants in gastric carcinomas: first clues to a role of survivin-2B in tumour progression. Br J Cancer, 2002,86(5):737-743.
42. Newton R,Kuitert LM,Slater DM,et al.Cytokine induction of cytosolic phospholipase A2 and cyclooxygenase-2 mRNA is suppressed by glucocorticoids in human epithelial cells.Life Sci, 1997,60(1):67-78.
43. Kawaguchi Y, Sato C,Hasegawa T, et al.Intraarticular osteoid osteoma associated with synovitis:a possible role of cyclooxygenase-2 expression by osteoblasts in the nidus. Modern Pathology,2000,13(10):1086-1091.
44. Kiang JG, Kiang SC, Juang YT, et al. N(omega)-nitro-L-arginine inhibits inducible HSP-70 via Ca(2+), PKC,and PKA in human intestinal epithelial T84 cells. Am J Physiol Gastrointest Liver Physiol,2002,282(3):415-423.
45．黄培堂，俞炜源，陈添弥等译．PCR技术实验指南．北京：科学出版社，1998：88-94．
46. Carmichaei J, Mitchell JB, DeGraff WG, et al. Chemosensitivity testing of human lung cancer cell lines using the MTT assay. Br J Cancer, 1988,57(6):540-547.
47. Mosmann T.Papid colometric assay for cellular growth and survival,Application to prolife ration and cytotoxicity assays.J Immun Method,1983,65(1):55-64.
48. Wyllie AH, Morris RG, Smith AL, et al. Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol,1984,142(1):67-77.
49. Ratan RR, Murphy TH, Baraban JM. Oxidative stress induces apoptosis in embryonic cortical neurons. J Neurochem,1994,62(1):376-379.
50. Schwartz LM, Kosz L, Kay BK. Gene activation is required for developmentally programmed cell death. Proc Natl Acad Sci USA,1990,87(17):6594-6598.
51. Borner MM, Myers CE, Sartor O, et al. Drug-induced apoptosis is not necessarily dependent on macromolecular synthesis or proliferation in the p53-negative human prostate cancer cell line PC-3. Cancer Res,1995 55(10):2122-2128.
52. Martin SJ. Protein or RNA synthesis inhibition induces apoptosis of mature human CD4+ T cell blasts. Immunol Lett,1993,35(2):125-134.
53. Martin SJ. Apoptosis: suicide, execution or murder? Trends Cell Biol, 1993,3(5): 141-144.
54. Fernandes RS,Cotter TG.Activation of a calcium magnesium independent endonu-clease in human leukemic cell apoptosis. Anticancer Res,1993,13(5A):1253-1259.
55. Huschtacha LI,Teither TM,Auderson CE,et al.Identification of apoptotic and necrotic human leukemia cells by flow cytometry.Exp cell Res,1994,12(1):167-172.
56. Boise LH, Gonzalez-Garcia M, Postema CE, et al. bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death.Cell,1993,74(4):597-608.
57. Mercatante DR, Mohler JL, Kole R.Cellular response to an antisense-mediated shift of Bcl-x pre-mRNA splicing and antineoplastic agents. J Biol Chem,2 002,277(51): 49374-49382.
58. Beardsmore DM,Verbeke CS,Davies CL, et al.Apoptotic and proliferative indexes in esophageal cancer:predictors of respinse to neoadjuvant therapy apoptosis and proliferation in eaophageal cancer.J Gastriointestinal Surg,2003,7(1):77-87.
59. Ikeguchi M, Liu J, Kaibara N. Expression of survivin mRNA and protein in gastric cancer cell line (MKN-45) during cisplatin treatment. Apoptosis,2002,7(1):23-29.
60. Lu B, Mu Y, Cao C, et al. Survivin as a therapeutic target for radiation sensitization in lung cancer. Cancer Res,2004,64(8):2840-2845.
61. Sun Y, Tang XM,Half E,et al.Cyclooxygenase-2 overexpression reduces apoptotic suscdptibility by inhibiting the cytochromec dependent apoptotic pathwqy in human colon cancer cells.Cancer Res,2002,62(21):6323-6328.
62．王枫，于芳，曹瑞，等．HSP70 高表达对K562细胞化疗敏感性研究．中国公共卫生，2003，19(2)：141-143
63. Kampinga HH.Hyperthermia,thermotolerance and topoisomerase inhibitors.Bfint J Can,1995,72(2):333-338.
64. Oesterreich S,Weng CN,Qiu M,et al.The small heat shock proteins HSP27 is correlated with growth and drug resistance in human breast cancer cell lines.Cancer Res,1993,53(19): 4443-4448.
65. Krysan K, Merchant FH,Zhu L, et al.COX-2-cependent stabilization of survivin in non small cell lung cancer.FASEB J,2004,18(1):206-208.
66. Barnes N,Haywood P, Flint P, et al.Survivin expression in insitu and invasive breast cancer relates to COX-2 expression and DCIS recurrence.Br J Cancer,2006, 94(2): 253-258.
1. Schena M,Shalon D,Hcllcr R,ct al.Parallel human gcnome analysis:microarray based expression monitoring of 1000 genes.Proc Natl Acad Sci USA,1996,93(20): 10614 -10619.
2. Leethanakul C,Patcl V, Gillespic J,et al.Distinct pattern of expression of differentiation and growth-related genes in squamous cell cancinomas of the head and neck revealed by the use of laser capture microdisscction and cDNA arrays.Oncogcnc, 2000,19(28): 3220-3224.
3. Smid-Koopman E,Blok LJ,Chadha-Ajwani S,et al. Genc expression profiles of human endometrial cancer samples using a cDNA-expression array technique: assessment of an analysis method. Br J Cancer,2000,83(2):246-251.
4. Zhou Y, Gwadry FG, Reinhold WC,et al.Transcriptional regulation of mitotic genes by camptothecin-induced DNA damagc:microarray analysis of dose and time-dependent effects.Cancer Res,2002,62(2): 1688-1695.
5. Pastinen T, Raitio M,Lindroos K, et al. A system for specific, high throughput genotyping by allele specific primer extension on microarrays.Genome Res, 2000,10 (7):1031-1042.
6. Chee M,Yang R,Hubbell E,et al.Accessing genetic information with high-density DNA arrays.Science, 1996,274:610-614.
7．陈亚利，陆祖宏．微芯片—生命科学领域的新工具．生物化学与生物物理进展，1998，25(6)：517-521．
8. Schena M,Shalon D,Dais RW, Brow PO.Quantitative monitoring of gene expression patterns with a complementary DNA microarray.Science,1995,270:467-470.
9. Gresham D,Rudeffer DM,Pratt SC, et al.Genome-wide detection of polymorphisms at nucleotide resolution with asingle DNA microarray. Science, 2006,311(5769): 1932- 1936.
10. Alcorta DA,Prakash K, Waga I,et al.Future molecular approaches to the diagnosis and treatment of glomerular disease.Semin Nephrol,2000,20(1):20-31.
11. Tennis M,Krishnan S,Bonner M,et al.p53 mutation analysis in breast tumors by a DNA microarray method.Cancer Epidemiol Biomarkers Prey,2006,15(1):80-85.
12. Pastore A,Carinci F, Pelucchi S.Genetic expression profiling of parotid neoplasms by cDNA microarrays.Acta Otorhinolaryngol Ital,2005,25(3):153-160.
13. Shroi DC,Teng S,Robinson G, et al.In vivo gene expression profile analysis of human breast cancer progression.Cancer Res,1999,59(22):5656-5661.
14. Anderson KM,Alrefar WA, Anderson CA,et al.A response of Panc-1 cells to cis-platinum, assessed with a cDNA array. Anticancer Res,2002, 22(1A): 75-81.
15. Freemantle SJ, Kerley JS, Olsen SL, et al. Developmentally-related candidate retinoic acid target genes regulated early during neuronal differentiation of human embryonal carcinoma. Oncogene,2002,21:2880-2889.
16. Sawids GP, Sherman-Baust CA, Beeker KG, et al.Development of a highly specialized cDNA array for the study and diagnosis of epithelial ovarian cancer. Cancer Res, 2002, 62(10):2923-2928.
17. Rhee CH,Hess K,Jabbur J,et al.cDNA expression array reveals heterogeneous gene expression profiles in three glioblastoma cell lines.Oncogene,1999,18(17):2711-2717.
18. Wang K, Gan I,Jefferry E, et al.Monitoring gene expression profile change in ovarian carcinomas using cDNA microarray. Gene, 1999,229(1 - 2): 101 - 108.
19. Xie L, Xul H,He Z, et al.ldentification of differentially expressed genes in nasopharyngeal carcinoma by means of the Atlas human cancer cDNA expression array.J Cancer Res Clin Oncol,2000,126(7):400 406.
20. Lee JS,Thorgeirsson SS.Functional and genomic implications of global gene expression profiles in cell lines from human hepatocellular cancer. Hepatology, 2002, 35(5):1134 1143.
21. Chong VZ,Young LT, Mishra RK.cDNA array reveale differential gene expression following chronic neuroleptic administration: Implications of synapsin Ⅱ in haloperidol treatment. J Neurochem,2002,82(6): 1533-1539.
22．孙德利，舒琦瑾．基因表达谱——中医药功能基因组学研究的思考．浙江中医学院学报，2002，26(1)：5-9．
23. Bortoli S,Renault V, Eveno E,et al.Gene expression profiling of human satellite cell during muscular aging using cDNA arrays.Gene,2003,321(2): 145-154.
24. Courtney S,Mossoba ME,Hammack TS,et al.Using PCR amplification to increase the confidence level of Salmonella typhimurium DNA microarray chip hybridization. Mol Cell Probes,2006,20(3): 163-171.
25. Galamb O,Molnar B,Tulassay Z.DNA chips for gene expression analysis and their application in diagnostics.Orv Hetil,2003,144(1):21-27.
26．王维民，刘延庆．基因芯片在肿瘤临床中的应用进展．肿瘤，2006，26(9)：870-872．
27. Ren CP, Lin WD,He ZW, et al.Differentially expressed gene profile of hCR2 transfected mouse cells before and after EBV infection and TPA treatment. Acta Biochim Biophys Sin,2001,33(1):105-111.
28. Hayase T, Yamamoto Y, Yamamoto K, et al.Microarray profile analysis of toxic cocaine induced alterations in the expression of mouse brain gene sequences:a possible 'protective' effect of buprenorphine.J Appl Toxicol,2004,24(1):15-20.
29. Sato H.Ishida S,Toda K,et al.New approaches to mechanism a nalysis for drug discovery using DNA microarray data combined with KeyMolnet. Cun Drug Discov Technol,2005,2(2):89-98.
30. Guzey C,Spigset O.Genotyping of drug targets:a method to predict adverse drug reaction?DrugSaf,2002,25(8):553-560.
31. Frye JG.Jesse T,Long F,et al.DNA microarray detection of antimicrobial resistance genes in diverse bacteria.Int J Antimicrob Agents,2006,27(2):138-151.
32. Stells H.Mechanisms and gene of cellular suicide.Science,1995,267(5023):1445-1449.
33. Chen KF, Lai YY, Sun HS, et al.Transcriptional repression of human cad gene by hypoxia inducible factor-1 alpha. Nucleic Acids Res,2005,33(16):5190-5198.
34. Yang D,Nakao M,Shichijo S,et al.Identification of a gene coding for a protein possessing shared tumor epitopes capable of inducing HLA-A24-restricted cytotoxic T lymphocytes in cancer patients.Cancer Res,1999,59(16):4056-4063.
35. Sasatomi T,Suefuji Y,Matsunaga K,et al.Expression of tumor rejection antigens in colorectal carcinomas.Cancer,2002,94(6): 1636-1641.
36. Tsuda N,Murayama K,Ishida H,et al.Expression of a newly defined tumor- rejection antigen SART3 in musculoskeletal tumors and induction of HLA class I-restricted cytotoxic T lymphocytes by SART3 derived peptides.J Orthop Res,2001,19(3): 346-351.
37. Stossi F,Barnett DH,Frasor J,et al.Transcriptional profiling of estrogen- regulated gene expression via estrogen receptor (ER) ERα or ERβ in human osteosarcoma cells: distinct and common target genes for these receptors. Endocrinology, 2003,145(7): 3473-3486.
38. Xia L,Nordman T,Olsson J,et al .The mammalia cytosolic selenoenzyme thioredoxin reductase reduces ubiquinone.A novel mechanism for defense against oxidative stress. J Biol Chem,2003,278(4):2141-2146.
39. Anestal K, Arner ES.Rapid induction of cell death by selenium compromised thioredoxin reductase 1 but not by the fully active enzyme containing selenocysteine. J Biol Chem,2003,278(18): 15966-15972.
40. Gromer S,Urig S,Becker K. The thioredoxin system--from science to clinic.Med Res Rev, 2004,24(1):40-89.
41．纪冬，成军，郭江，等．乙型肝炎病毒X蛋白上调硫氧还蛋白还原酶1基因表达的研究．胃肠病学和肝病学杂志，2005，14(1)：18-22．
42. Tamura T, Stadtman TC.A new selenoprotein from human lung adenocarcinoma cells: purification, properties, and thioredoxin reductase activity. Proc Natl Acad Sci USA,1996,93 (3): 1006-1011.
43. Gladyshev VN,Jeang KT, Stadtman TC.Selenocysteine, identified as the penultimate C-terminal residue in human T-cell thioredoxin reductase, corresponds to TGA in the human placental gene. Proc Natl Acad Sci USA,1996,93(12):6146-6151.
44. Berggren M,Gallegos A, Gasdaska JR,et al.Thioredoxin and thioredoxin reductase gene expression in human tumors and cell lines, and the effects of serum stimulation and hypoxia. Anticancer Res, 1996,16 (6B):3459-3466.
45. Kahlos K, Soini Y, Saily M,et al.Up-regulation of thioredoxin and thioredoxin reductase in human malignant pleural mesothelioma.lnt J Cancer,2001,95(3): 198-204.
46. Nilsson J, Soderberg O,Nilsson K, et al.Thioredoxin prolongs survival of B-type chronic lymphocytic leukemia cells.Blood, 2000,95(4): 1420-1426.
47. Chen Yan,Cai J,Murphy TJ,et al.Overexpressed human mitochondrial thioredoxin confers resistance to oxidant-induced apoptosis in human osteosarcoma cells.J Biol Chem, 2002,277(36):33242-33248.
48. Ungerstedt JS, Sowa Y, Xu WS, et al.Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors. Proc Natl Acad Sci USA,2005, 102(3):673-678.
49. Renschler MF. The emerging role of reactive oxygen species in cancer therapy. Eur J Cancer,2004,40(13):1934-1940.
50. Davis W, Jr, Ronai Z,et al.Tew cellular thiols and reactive oxygen species in drug-induced apoptosis. J Pharmacol Exp Ther.Vol, 2001,296(1):1-6.
51. Hulmej T.Coppock EA,Felipe A,et al.Oxygen sensitivity of cloned voltage-gated K~+ channels expressed in the pulmonary vasculature.CircRes,1999,85(6):489-497.
52. Semenza GL.HIF-l:mediator of physiological and pathophysiological responsis to hypoxia.J Apply Physiol,2000,88(4):1474-1480.
53. Yan L,Figueroa DJ,Austin CP,et al. Expression of voltage-gated potassium channels in human and rhesus pancreatic islets.Diabetes,2004,53:597-607.
54. Hall MC,Matson SW.Helicase motifs:the engine that powers DNA unwinding.MoI Microbiol,1999,24(5):867-877.
55. Silvermen E,Edwalds GG,Iin RJ.DexD/H box protein and their partners:helping RNA helicases unwind.Gene,2003,312:l-16.
56. Henning D, So RB, Jin R,et al. Silencing of RNA helicase II/Gualpha inhibits mammalian ribosomal RNA production.J Biol Chem,2003,278(52):52307-52414.
57. Cho-Chung YS,Pepe S,Clair T,et al.cAMP- dependent protein kinase role in normal and malignant growth.Crit Rev Oncol Hematol,1995,21(l-3):33-61.
58. Miller WR,Watson DM,Jack W,et al.Tumor cyclic AMP binding proteins:an independent prognostic factor for disease recurrence and survival in breast cancer. Breast Cancer Res Treat,1993,26(1):89-94.
59. Ciardiello F,Damiano V,Bianco C,et al.Cooperative antiproliferative effects 8-C1-cAMP and 528 antiepidermal growth factor receptorm onoclonal antibody on human cancer cells.Clin Cancer Res,1995,l(2):161-167.
60. Murai T.Leucine aminopeptidase(LAP).Rinsho Byori,2001,116(suppl):110-116.
61. Kawai M,Hara Y,Miyazato I,et al.Aberrantly truncated isoform of serum CD13 in a family with high serum aminopeptidase N(CD13) activity.Clin Chem,2001, 47(2): 223-230.
62. Varshavsky A.The N-end rule:functions,mysteries uses. Proc Natl Acad Sci USA, 1996, 93(22): 12142-12149.
63. Qu CK.Role of the SHP-2 tyrosine phosphatase in cytokine-induced signaling and cellular response.Biochim Biophys Acta,2002,1592(3):297-301.
64. Carlesso N,Frank DA,Griffin JD.Tyrosyl phosphorylation and DNA binding activity of signal tuansducers and activators of transcription (STAT) proteins in hemetopoietic cell lines transformed by Bcr/Abl. Exp Med,1996,183:811-820.
65. Neel BG,Gu H,Pao L.The'Shp'ing news:SH2 domain-containing tyrosine phospha-tases tases in cell signaling.Trends Biochem Sci,2003,28(6):284-293.
66. Radke I,Gotte M,Kersting C,et al.Expression and prognostic impact of the protein tyrosine phosphatases PRL-1, PRL-2, and PRL-3 in breast cancer.Br J Cancer,2006, 95(3):347-354..
67. Sun JP,Wang WQ,Yang H,et al. Structure and biochemical properties of PRL-1, a phosphatase implicated in cell growth, differentiation, and tumor invasion. Biochemistry, 2005,44(36):12009-12021.
68. Veale M,Raab M,Li Z,et al.Novel isoform of lymphoid adaptor FYN-T-binding protein (FYB-130) interacts with SLP-76 and up-regulates interleukin 2 production.J Biol Chem, 1999,274(40):28427-28435.
69. Duke-Cohan JS,Kang H,Liu H,et al.Regulation and function of SKAP-55 non-canonical motif binding to the SH3c domain of adhesion and degranulation-promoting adaptor protein.J Biol Chem, 2006,281(19):13743-13750.
70. Kaur M,Pop M,Shi D,et al. hHR23B is required for genotoxic-specific activation of p53 and apoptosis. Oncogene,2007,26(8): 1231-1237.
71. Hsieh HC,Hsieh YH,Huang YH,et al.HHR23A, a human homolog of Saccharomyces cerevisiae Rad23, regulates xeroderma pigmentosum C protein and is required for nucleotide excision repair. Biochem Biophys Res Commun,2005,335(1): 181-187.
72. Erez A,Perelman M,Hewitt SM,et al.Sil overexpression in lung cancer characterizes tumors with increased mitotic activity. Oncogene,2004,23(31):5371-5377.
73. Favre C,Carnovale CE,Monti JA.Inhibition by interferona-2b of rat liver regeneration: effect on ornithine decarboxylase and total protein synthesis.Biochemical Pharmacology, 2001,61(12):1587-1593.
74. Mimorl K, Mori M,Shiraishi T,et al.Analysis of ornithine decarboxylase messenger ribonucleic acid expression in colorectal carcinoma.Dis Colon Rectum, 1997, 40 (9): 1095-1100.
75. Sahu S,Khadeer M,Bai G,et al.Over expression of the ZIPl zine transporter induces an osteogenic phenotype in mesenchymal stem cells.Bone,2006,38(2):181-198.
76. Taylor KM.LIV1 breast cancer protein belongs to new family of histidine rich membrane proteins with potential to control intracellular Zn~(2+) homeostasis.IUBMB Life,2000,49(4):249-253.
77. Kasper G,Weiser AA,Rump A,et al.Expression levels of the putative zinc transporter LIV-1 are associated with a better outcome of breast cancer patients.Int J Cancer,2005, 117(6):961-973.
78. Chen TC,Holick MF,Lokeshwar BL,et al.Evaluation of vitamin D analogs as therapeutic agents for prostate cancer.Recent Results Cancer Res, 2003,164:273-288.
79. Chrng JW,Jeon JH,Yoon SR,et al.Vitamin D3 upregulated protein (VDUP1) is a regulator for redox signaling and stress-mediated diseases.J Dermatology, 2006, 33 (10):662-669.
80. Minn AH,Hafele C,Shalev A. Thioredoxin-interacting protein is stimulated by glucose through a carbohydrate response element and induces beta-cell apoptosis. Endocrinology,2005,146(5):2397-2405.
81. Goldberg SF,Miele ME,Hatta N,et al.Melanoma metastasis suppression by chromosome 6 evidence for a pathway regulated by CRSP3 and TXNIP.Cancer Res,2003,63:432-440.
82. Huang L,Pardee AB.Suberoylanilide hydroxamic acid as a potential therapeutic agent for human breast cancer treatment.Mol MED,2000,6(10):849-866.
83. Prudencio J,Adutsu N,Benlimame N,et al.Action of low calcemicl alpha ,25-dihydroxyvitamin D3 analogue EB1089 in head and necd squamous cell carcinoma.J Natl Cancer,2001,93(10):745-753.
84. Lin R,Wang TT,Miller WH,et al.Inhibition of F-box protein p45~(SKP2) expression and stabilization of cyclin-dependent kinase inhibitor p27~(KIP1) in vitamin D analog-treated cancer cells.Endocrinology,2003,144(3):749-753.
85. Tartaglia J,Bonnet MC,Berinstein N,et al.Therapeutic vaccines against melanoma and colorectal cancer.Vaccine,2001,19(17-19):2571-2575.
86. Juretic A,Spagnoli GC,Schultz TE,et al.Cancer/testis tumour-associated antigens: immunohistochemical detection with monoclonal antibodies.Lancet Oncol,2003, 4(2): 104-109.
87. Breitling R, Laubner D, Clizbe D,et al. Isopentenyl-diphosphate isomerases in human and mouse: evolutionary analysis of a mammalian gene duplication.J Mol Evol,2003, 57(3):282-291.
88. Tabuchi Y,Ando H,Tadasaki I,et al.Identification of genes responsive to low intensity pulsed ultrasound in a human leukemia cell line Molt-4.Cancer Lett,2007, 246 (1-2): 149-156.
89. Goldberg J.Structural basis for activation of ARF GTPase: mechanisms of guanine nucleotide exchange and GTP-myristoyl switching.Cell,1998,95(2):237-248.
90. Min DS, Kwon TK, Park WS et al. Neoplastic transformation and tumorigenesis associated with overexpression of phospholipase D isozymes in cultured murine fibroblasts.Carcinogenesis,2001,22(10):1641-1647.
91. Takahashi Y,Nagata T,Ishii Y,et al.Up-regulation of vitamin D3 up-regulated protein 1 gene in response to 5-fluorouracil in colon carcinoma SW620.Oncol Rep,2002, 9(1):75-79.
1. Chen JQ, Zhan WH, He YL, et al. Expression of heparanase gene, CD44v6, MMP-7 and nm23 protein and their relationship with the invasion and metastasis of gastric carcinomas. World J Gastroenterol,2004,10(6):776-782.
2. Nocito A, Kononen J,Kallioniemi OP, et al.Tissue microarrays (TMAs) for high-throughput molecular pathology research.Int J Cancer,2001,94(1):l-5.
3．周小鸽，张劲松，张小平，等．组织芯片．中华病理学杂志，2002，31(1)：70-72．
4. Battifora H. The multitumor (sausage) tissue block: novel method for immunohistochemical antibody testing. Lab Invest,1986,55:244-248.
5. Kononen J,Bubendorf L, Kalliviemi A, et al.Tissue microarrays for high-through put molecular profiling of tumor specimens.Nat Med,1998,4(7):844-847.
6. Manley S,Mucci NR, de Matzo AM,et al.Relational database structure to manage high-denaily tissue microarray data and images for pathology stadies focusing on clinical outcome:The prostate specialized program of research excellence model.Am J Pathol,2001,159(3):837-843.
7. Mahotka C,Wenzel M,Springer E, et al.Survivin-deltaEx3 and survivin-2B:two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties. Cancer Res,1999,59(24):6097-6102.
8. lkehara M, Oshita F, Kameda Y, et al. Expression of survivin correlated with vessel invasion is a marker of poor prognosis in small adenocarcinoma of the lung.Oncol Rep, 2002,9(4):835-838.
9. Tanaka K, Iwamoto S, Gon G, et al. Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res,2000,6(1): 127-134.
10. Wakana Y, Kasuya K, Katayanagi S, et al. Effect of survivin on cell proliferation and apoptosis in gastric cancer. Oncol Rep,2002,9(6):1213-1218.
11. Kato J, Kuwabara Y, Mitani M, et al. Expression of Survivin in esophageal cancer: correlation with the prognosis and response to chemotherapy. Int J Cancer, 2001, 95(2):92-95.
12. Kallakury BV.Shechan CE,Ambros RA,et al.The progncsitid siginificance of P34cdc2 and cyclinDl protein expression in prostate adenocacinoma.Cancer,1997, 80(4): 753-763.
13. Shin S,Sung BJ,Cho YS,et al.An anti-apoptotic protein human surviving is a direct inhibitor of caspase 3 and caspase 7.Biochemistry,2001,40(4):1117-1123.
14. Chen J, Wu W, Tahir SK, et al. Down-regulation of Survivin by antisense oligonucleotides increases apoptosis, inhibits cytokinesis and anchorage-independent growth. Neoplasia, 2000,2(3):235-241.
15. Sarela AI, Macadam RC, Farmery SM, et al. Expression of the antiapoptosis gene, survivin,predicts death from recurrent colorectal carcinoma. Gut, 2000,46(5):645-650.
16. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, Survivin, expressed in cancer and lymphoma. Nat Med,1997,3(8):917～921.
17. Tsuburaya A, Noguchi Y, Yoshikawa T, et al. An anti-apoptosis gene, Survivin and telomerase expression in gastric cancer. Hepatogastroenterology, 2002, 49(46): 1150-1152.
18. Miyachi K, Sasaki K, Onodera S, et al. Correlation between Survivin mRNA expression and lymph node metastasis in gastric cancer. Gastric Cancer, 2003,6(4): 217-224.
19. Chen WS,Wei SJ,Liu JM,et al.Tumor invasiveness and liver metastasis of colon cancer cell correlated with cyclooxygenase-2(COX-2) expression and inhibited by a COX-2 seletive inhibitor,etodolac.Clin Cancer Res,2001,7(4):861-867.
20. Kinoshita T,Tadahashi Y,Sakashita T,et al.Growth stimulation and induction of epidermal growth factor receptor by overexpression of cyclooxygenases land 2 in human colon carcinoma cells.Biochim Biophys Acta,1999,1438(1):120-130.
21. Tsujii M,Kawano S,DuBois RN.Cycollxygenase-2 expression in human colon cancer cells increases metastatic potential.Proc Natl Acad Sci USA,1997,94(7):3336-3340.
22. O'Mahony CA,Beauchamp RD,Albo D,et al.Cyclooxygenase-2 alters transforming growth factor-beta 1 response during intestinal tumorigenesis.Surgery, 1999,126(2): 364-370.
23. Tucker ON, Dannenberg AJ, Yang EK,et al. Cyclooxygenase2 expression is up-regulated in human pancereatic cancer. Cancer Res,1999,59(5):987-990.
24. Liang JT, Huang KC, Jeng YM,et al. Microvessel density, cyclo-oxygenase 2 expression, K-ras mutation and p53 overexpression in colonic cancer. Br J Surg, 2004,91(3):355-361.
25. Xue YW,Zhang QF,Zhu ZB,et al.Expression of cyclooxygenase-2 and clinico-pathologic features in human gastric adenocarcinoma.Would J Gastroenterol, 2003,9: 250-253.
26. Ohno R, Yoshinaga K, Fujita T, et al. Depth of invasion parallels increased cyclooxygenase-2 levels in patients with gastric carcinoma.Cancer, 2001,91(10): 1876-1881.
27. Ellis RJ. Molecular chaperones: plugging the transportgap.Nature,2003,421(6925): 801- 802.
28. Zhang SHL,Wei SO,Li ST.Immunohistochemical study of heat shock protein 70 in mose endometrium during carlyregnancy.J Anat,2002,25(1):21-24.
29. Lauten M, Beger C, Gerdes K, et al. Expression of heat-shock protein 90 in glucocorticoid- sensitive and -resistant childhood acute lymphoblastic leukaemia. Leukemia,2003,17(8): 1551-1556.
30. O'Neill PA, Shaaban AM, West CR, et al.Increased risk of malignant progression in benign proliferating breast lesions defined by expression of heat shock protein 27. Br J Cancer, 2004,90(1):182-188.
31. Uozaki H, Ishida T, Kakiuchi C, et al. Machinami R. Expression of heat shock proteins in osteosarcoma and its relationship to prognosis. Pathol Res Pract,2000,196(10): 665-673.
32. Elpek GO, Karaveli S, Simsek T,et al. Expression of heat-shock proteins hsp27, hsp70 and hsp90 in malignant epithelial tumour of the ovaries. APMIS,2003,111(4):523-530.
33. Lambot MA, Peny MO, Fayt I, et al.Overexpression of 27-kDa heat shock protein relates to poor histological differentiation in human oesophageal squamous cell carcinoma. Histopathology, 2000,36(4):326-330.
34. Zuo DS, Dai J, Bo AH, et al. Significance of expression of heat shock protein90alpha in human gastric cancer. World J Gastroenterol, 2003,9(11):2616-2618.
35. Torronteguy C, Frasson A, Zerwes F, et al. Inducible heat shock protein 70 expression as a potential predictive marker of metastasis in breast tumors.Cell Stress Chaperones, 2006,11(1): 34-43.
36. Hwang TS, Han HS, Choi HK, et al. Differential, stage-dependent expression of Hsp70, Hsp110 and Bcl-2 in colorectal cancer. J Gastroenterol Hepatol ,2003,18(6): 690-700.
37. Noguchi T, Wada S, Takeno S, et al. Lymph node metastasis could be predicted by evaluation of macrophage infiltration and hsp70 expression in superficial carcinoma of the esophagus. Oncol Rep, 2003,10(5):1161-1164.
38. Cappello F, David S, Rappa F,et al. The expression of HSP60 and HSP10 in large bowel carcinomas with lymph node metastase. BMC Cancer,2005,5:139.
2. Vaux DL, Korsmeyer SJ.Cell death in development. Cell,1999,96(2):245-254.
3. Mahotka C,Wenzel M,Springer E,et al. Survivin-deltaEx3 and survivin-2B: two novel splice variants of the apoptosis inhibitor Survivin with different antiapoptotic properties. Cancer Res,1999,59(24):6097-6102.
4. He J,Agarwal ML,Larkin HE,et al.The induction of partial resistance to photodynamic therapy by the protooncogene BCL-2.Photochenl Photobiol,1996,64(5):845-852.
5. Kamesaki S,Kamesaki H,Jorgensen TJ,et al.bcl-2 protein inhibits etoposide-induced apoptosis through its effects on events subsequent to topoisomerase- II induced DNA strand breaks and their repair.Cancer Res,1993,53:4251-4256.
6. Shimizu S,Eguchi Y.Kosada H,et al.Prevention of hypoxia-induced cell death by Bcl-2 and Bcl-xl.Nature,1995,374(6525):811-813.
7. Wang H.Combined effect of docetaxel and cisplatin for non-small cell lung cancer cell lines in vitro.Nagoya J Med Sci,2000,63(3-4):129-137.
8. Takahashi Y,Nagata T,Ishii Y,et al.Up-regulation of vitamin D3 up-regulated protein 1 gene in response to 5-fluorouracil in colon carcinoma SW620.Oncol Rep,2002, 9(1):75-79.
9. Seewaldt VL,Mrozek K , Dietze EC,et al.Human papillomavirus type 16E6 inactivation of p53 in normal human mammary epithelial cells promootes tamoxifen-mediated apoptosis.Cancer Res,2001,61(2):616-624.
10. Chu W.Pak BJ,Bani MR,et al.Tyrosinase-related protein 2 as a mediator of melanoma specific resistance to cis-diamminedichloroplatinum( II): therapeutic implications. Oncogene,2000,19(3):395-402.
11. Miyake H,Hara S,Arakawa S,et al.Optimal timing and dosage of chemotherapy as a combined treatment with androgen withdrawal in the human prostate LNCaP tumour model.Br J Cancer,2001,84(6):859-863.
12. Buckley AR.Lessons from anticancer research might provide new insights into mechanisms of hormone action.Trends Endocrinol Metab,2001,12(3):87-89.
13. Fulda S,Susin SA,Kromer G,et al.Molecular ordering of apoptosis induced by anticancer drugs in neuroblastoma cells.Cancer Res,1998,58:4453-4460.
14. Duque G,Elabdaimi K,Henderson JE,et al.Vitamin D inhibits Fas ligand induced apoptosis in human osteoblasts by regulating components of both the mitochondrial and Fas related pathways.Bone,2004,35(1):57-64.
15. Wagner N,Wagner KD,Schley G,et al.l,25-dihydroxyvitaminD3-indrced aoptosis of retinoblastoma cells is associated with reciprocal changes of bcl-2 and bax.Exp Eye Res,2003,77(1):1-9.
16. Brenner C, Kroemer G. Mitochondria:the death signal integrators. Science, 2000, 289(5482):1150-1151.
17. Liu X,Kim CN,Yang J,et al.Induction of apoptosis program in cell-free extracts: requirement for dATP and cytochrome C.Cell,1996,86(1):147-157.
18. Jiang X,Wang X.Cytochrome c promotes caspase-9 activation by inducing nucleotide binding to Apaf-1.J Biol Chem,2000,275:31199-31203.
19. Lum JJ, Bbawor DE,Kong M,et al.Growth factor regulation of autophage and cell survival in the absence of apoptosis.Cell,2005,120(2):237-248.
20. Ruled SJ,Renatus M,Schwarzenbacher R,et al.Structural basis for the inhibition of caspase 3 by XIAP.Cell,2001,104(5):791-800.
21. Suzuki Y,Nakabayashi Y,Takahashi R.Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effcet in Fas-induced cell death.Proc Natl Acad Sci USA,2001,98(15):8662-8667.
22. Du C,Fang M,Li Y,et al.Smac,a mitochondnal protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition.Cell,2000,102(1):33-42.
23. Srinivasula SM,Hegde R,Saleh A,et al.A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis.Nature,2001, 410(6824):112-116.
24. Chai J,Du C,Wu JW,et al.Structural and biochemical basis of apoptotic activation by Smac/DIABLO.Nature,2000,406(6798):855-862.
25. Liu ZH,Sun C,Olejniczak ET,et al.Structural basis for binding of Smac DIABLO to the XIAP BIR3 domain.Nature,2000,408(6815):1004-1008.
26. Miramar MD,Costantini P,Ravagnan L,et al.NADH oxidase activity of mitochondrial apoptosis-inducing factor.J Biol Chem,2001,276(19): 16391-16398.
27. Susin SA,Lorenzo Hk,Zamzami N,et al.Molecular characterization of mitochondrial apoptosis-inducing factor.Nature,1999,397(6718):441-446.
28. Woo RA,Melure KG, Lees-Miller SP,et al.DNA-dependent protein kinase acts upstream of p53 in response to DNA damage.Nature,1998,394(6694):700-704.
29. Kim R,Ohi Y,Inoue H,et al.Enhancement of chemotherapeutic agents induced-apoptosis associated with activation of c-Jun N-terminal kinase 1 and caspase 3 (CPP32) in bax-transfected gastric cancer cells.Anticancer Res,2000,20(1A):439-444.
30. Wright SC,Wang H,Wei QS,et al.Bcl-2 mediated resistance to apoptosis is associated with glutathione-induced inhibition of Ap24 activation of nuclear DNA fragmentation. Cancer Res,1998,58(23):5570-5576.
31. Sim BKL, MacDonald NJ, Edward RG Angiostatin and endostatin: endogenous inhibitors of tumor growth.Cancer Metastasis Rev,2000,19(l,2):181-190.
32. Eskens F.Angiogenesis inhibitors in clinical development:where are we now and where are we going?Br J Cancer, 2004,90(1): 1-7.
33. Li C,Thompson CB.DNA damage,deamidation,and death.Science,2002,298 (5597): 1346-13467.
34. Pozniak CD,Radinovic S,Yang A,et al.An anti-apoptotic role for the p53 family member, p73,dufing developmental neuron death. Science,2000,289 (5477):304-306.
35. Fulda S,Meyer E, Friesen C,et al.Cell type specific involvement of death receptor and mitochondfial pathways in drug-induced apootosis.Oncogene,2001,20(9):1063-1075.
36. Timmer T, Vries EGE,Jong S.Fas receptor mediated apoptosis:a clinical application.Pathol,2002,196(2): 125-134.
37. Wajant H.The Fas signaling pathway:more than a paradigm.Science,2002,296(5573): 1635-1636.
38．任含平，施广霞．FAS信号转导与其抑制机．国外医学生理、病理科学与临床分册,2004,24(4)：329-330．
39. Kaufmann SH,Earnshaw WC.Induction of apoptosis by cancer chemotherapy.Exp Cell Res,2000,256(1):42-49.
40. Pimentel-Muinos FX,Seed B.Regulated commitment of TNF receptor signaling:a molecular switch for death or activation.Immunity,1999,11(6):783-793.
41. Wang T, Zhang X,Li JJ.The role of NF-kappaB in the regulation of cell stress responses.Tnt Immunopharmacol,2002,2(11): 1509-1520.
42. Wiley SR,Schoole YK, Smolak PJ,et al.Identification and characterization of a new member of the TNF family that induces apoptosis.Immunity,1995,3(6):673-682.
43．张军，马远方，赵粤萍，等．死亡受体 5 在肝癌细胞系及肝细胞系表面的表达．中国肿瘤临床,2006,33(5)：287-289．
44. Kaise N, Edelman IS. Calcium dependence of glueocorticoid-induced lymphocytolysis.Proc Natl Acad Sci USA.1977,74(29):638-642.
45. Yamagachi T, Chaltopadhyay N,Brown EM.G protein-coupled extra-cellular Ca~(2+) (Cao~(2+))-sensing receptor(CaR):Roles in cell signaling and control of diverse cellular functions.Adv Pharmacol,2000,47:209-213.
46．郭静，蒲咏梅，张东才．钙离子信号与细胞凋亡．生物物理学报,2005,21(1)：1-18．
47. McConkey DJ,Orrenius S.The role of calcium in the regulation of apoptosis.Biochem Biophys Res Commu,1997,239(2):357-366.
48. Wang E,Lee MD,Dunn KW.Lysosomal accumulation of drugs in drug-sensitive MES-SA but not multidrug-resistant MES-SA/Dx5 uterine sarcoma cells.J Cell Physiol, 2000;184(2):263-274.
49. Barry MA,Reynolds JE,Eastman A.Etoposide indued apoptosis in human HL-60 cells is associated with intracellular acidification.Cancer Res,1993,53(10):2349-2357.
50. Gottlieb RA.Apoptosis induced in Jurkat cells by several agents is preced by intracellular acidification.Proc Natl Acad Sci USA,1996,93(2):654-658.
51.Ashkenazi A,Dixit VM. Death receptors: signaling and modulation. Science, 1998, 281(5381):1305-1308.
52. Evan G,Iittlewood T. A matter of life and cell death.Science,1998,281(5381): 1317-1322.
53. LaCasse EC,Baird S,Korneluk RG,et al.The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene,1998,17(25):3247-3259.
54. Mosser DD,Caron AW,Bourget L,et al.Role of human heat shock protein hsp70 in protection against stress-induced apoptosis. Mol Cell Biol,1997,17(9):5317-5327.
55. Ebert MPA,Schafer C, Chen J,et al. Protective role of heat shock protein 27 in gastric mucosal injury.J patholo,2005,207(2): 177-184.
56. Yeo M,Kim DK,Kim YB,et al.Selective Induction of Apoptosis with Proton Pump Inhibitor in Gastric Cancer Cells.Clin Cancer Res,2004,10:8687-8696.
57. Deveraux QL,Reed JC. LAP family proteins-suppressors of apoptosis.Gene Dev, 1999.13(3):239-252.
58. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, Survivin, expressed in cancer and lymphoma. Nat Med,1997,3(8):917-921.
59. Rohayem J,Diestelkoetter P,Weigle B,et al.Antibody response to the tumor associated inhibition of apoptosis protein Survivin cancer patients.Cancer Res,2000,60(7):1815-1817.
60. Bao R, Connolly DC, Murphy M,et al. Activation of cancer-specific gene expression by the Survivin promoter. J Natl Cancer Inst,2002,94(7):522-528.
61. Suzuki A, Ito T, Kawano H, et al.Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death. Oncogene,2000,19(10):1346-1353.
62. Verdecia MA, Huang Hk, Dutil E.et al.Structure of the human anti-apoptotic protein Survivin reveals a dimeric arrangement.Nature Structura Biology,2000,7(7):602-608.
63. Tamm I,Wang Y.Sausville E,et al.IAP family protein Survivin inhibits caspase activity and apoptosis induced by Fas(CD95),Bax,caspases,and anticancer drugs.Cancer Res, 1998,58(23):5315-5320.
64. Ikeguchi M,Ueda T,Sakatani T,et al.Expression of Survivin messenger RNA correlates with poor progenosis patients with hepatocellular carcinoma.Diagn Mol Pathol, 2002,ll(1):33-40.
65. Velculescu VE,Madden SL,Zhang L,et al.Analysis of human transcriptomes.Nat Genet, 1999,23(4):387-388.
66. Yamamoto T.Tanidewa N.The role of Survivin as a new target of diagnosis and treatment in human cancer.Med Electron Microsc,2001,34(4):207-212.
67. Fuller KJ,Issels RD,Slosman DO,et al.Cancer and the heatshock response.Eur J Cancer, 1994,30A(12):1884-1891.
68. Helmbrecht K, Zeise E, Rensing L. Chaperones in cell cycle regulation and mitogenic signal transduction: a review.Cell Prolif,2000,33(6):341-365.
69. Jolly C, Morimoto RI. Role of the heat shock response and molecular chaperones in oncogenesis and cell death.J Natl Cancer Inst,2000,92(19): 1564-1572.
70. Ellis RJ.Molecular chaperones:plugging the transportgap.Nature,2003,421(6925):801-802.
71. Papp E, Nardai G, Soti C, Csermely P. Molecular chaperones, stress proteins and redox homeostasis.Bio factors 2003,17:249-257.
72. Zhang SHL,Wei SO,Li ST.Immunohistochemical study of heatshock protein 70 in mouse endometrium during carly regnancy.J Anat,2002,25(1):21-24.
73. Smith WL,Garavito RM, DeWitt DL. Prostaglandin endoperoxide H synthases (cyclooxygenase)-l and -2. J Biol Chem.1996,271:33157-33160.
74. Chen WS,Wei SJ,Liu JM,et al.Tumor invasiveness and liver metastasis of colon cancer cell correlated with cyclooxygenase-2(COX-2) expression and inhibited by a COX-2-seletive inhibitor,etodolac.Int J Cancer,2001,91(6):894-899.
75. Ratnasinghe D,Tangrea JA,Roth MJ,et al.Expression of the cyclo-oxygenase-2 in human adenocarcinomas of the gastric cardia and corpus.Oncol Rep,1999,6:965-968.
76. Tucker ON, Dannenberg AJ,Yang EK,et al. Cyclo-oxygenase-2 expression is up-regulated in human pancreatic cancer. Cancer Res, 1999,59:987-990.
77. Uefuji K, Ichikura T, Mochizuki H,et al. Expression of cyclooxygenase2 in human gastric adenomas and adenocarcinomas.Surg Oncol,2001,76(1):26-30.
78. Fujita T, Matsui M, Takaku K, et al. Size and invasion dependent increase in cyclo-oxygenase-2 levels in human colorectal carcinomas.Cancer Res, 1998, 58(21):4823-4826.
79. Kawabe A, Shimade Y, Uchida.et al. Expression of cyclooxygenase-2 in primary and remnant gastric carcinoma.Surg Oncol, 2002,80(2):79-88.
80. Wyllie AH, Morris RG, Smith AL, et al. Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol,1984,142(1):67-77.
81. Ratan RR, Murphy TH, Baraban JM. Oxidative stress induces apoptosis in embryonic cortical neurons. J Neurochem,1994,62(1):376-379.
82. Schwartz LM, Kosz L, Kay BK. Gene activation is required for developmentally programmed cell death. Proc Natl Acad Sci USA,1990,87(17):6594-6598.
83. Martin SJ. Protein or RNA synthesis inhibition induces apoptosis of mature human CD4+ Tcell blasts. Immunol Lett,1993,35(2):125-134.
84. Moule AJ, Young WG, Adkins KF. Early cellular events in an actinomycin D-created dentin niche in the rat incisor. J Oral Pathol Med,1993,22(4):159-167.
85. Pagliacci MC, Migliorati G, Smacchia M, et al. Cellular stress and glucocorticoid hormones protect 1929 mouse fibroblasts from tumor necrosis factor alpha cytotoxicity. J Endocrinol Invest,1993,16(8):591-599.
86. Waring P. DNA fragmentation induced in macrophages by gliotoxin does not require protein synthesis and is preceded by raised inositol triphosphate levels. J Biol Chem, 1990,265(24):14476-14480.
87. Borner MM, Myers CE, Sartor O, et al. Drug-induced apoptosis is not necessarily dependent on macromolecular synthesis or proliferation in the p53-negative human prostate cancer cell line PC-3. Cancer Res,1995,55(10):2122-2128.
88. Vaux DL. Toward an understanding of the molecular mechanisms of physiological cell death. Proc Natl Acad Sci USA,1993,90(3):786-789.
89. Martin SJ.Apoptosis:suicide,execution or murder? Trends Cell Biol, 1993,3(5): 141-144.
90. Fernandes RS, Cotter TG. Activation of a calcium magnesium independent endonuclease in human leukemic cell apoptosis.Anticancer Res,1993,13(5A): 1253-1259.
91. Olsson A, Diaz T, Aguilar-Santelises M,et al. Sensitization to TRAIL-induced apoptosis and modulation of FLICE-inhibitory protein in B chronic lymphocytic leukemia by actinomycin D. Leukemia,2001,15(12):1868-1877.
1. Nicholson DW, Thornberry NA.Apoptosis life and death decision. Science. 2003, 299(5604): 214-215.
2. Evan G, Littlewood T.A matter of life and cell death.Science, 1998,281(5381): 1317-1322.
3. Nicholson DW.From bench to clinic with apoptosis-based therapeutic agents. Nature, 2000,407(6805):810-816.
4. Green DR,Evan GI.Amatter of life and death.Cancer Cell,2002,1(1):19-30.
5. Ferber D.Cancer research.A new way to combat therapy side effects.Science, 1999, 285(5434): 1651-1653.
6. Kiechle FL, Zhang X.Apoptosis:biochemical aspects and clinical implications. Clin Chim Acta,2002,326(1-2):27-45.
7. Wang H.Combined effect of docetaxel and cisplatin for non-small cell lung cancer cell lines in vitro.Nagoya J Med Sci,2000,63(3-4):129-137.
8. Okada E,Murai Y, Matsui K, et al. Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients. Cancer Lett, 2001,163(1):109-116.
9. Mahotka C,Wenzel M,Springer E,et al.Survivin-deltaEx3 and survivin-2B:two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties.Cancer Res,1999,59(24):6097-6102.
10. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, Survivin, expressed in cancer and lymphoma. Nat Med,1997,3(8):917-921.
11. Deveraux QL, Reed JC.IAP family proteins-suppressors of apoptosis.J Genes Dev,1999, 13(3):239-252.
12. Shin S, Sung BJ, Cho YS, et al. An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and-7. Biochemistry, 2001,40(4):1117-1123.
13. Tamm I, Wang Y, Sausville E, et al. IAP-family protein Survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res,1998,58(23):5315-5320.
14. Kato J, Kuwabara Y, Mitani M, et al. Expression of Survivin in esophageal cancer: correlation with the prognosis and response to chemotherapy. Int J Cancer,2001,95 (2): 92-95.
15. Wakana Y, Kasuya K, Katayanagi S, et al. Effect of Survivin on cell proliferation and apoptosis in gastric cancer. Oncol Rep, 2002,9(6):1213-1218.
16. Fornaro M, Plescia J, Chheang S, et al. Fibronectin protects prostate cancer cells from tumor necrosis factor-alpha-induced apoptosis via the AKT/survivin pathway. J Biol Chem,2003,278(50):50402-50411.
17. Tanaka K, Iwamoto S, Gon G, et al. Expression of Survivin and its relationship to loss of apoptosis in breast carcinomas.Clin Cancer Res,2000,6(1):127-134.
18. Ikehara M, Oshita F, Kameda Y, et al. Expression of Survivin correlated with vessel invasion is a marker of poor prognosis in small adenocarcinoma of the lung. Oncol Rep,2002,9(4):835-838.
19. Kawasaki H, Altier DC, Lu CD, et al. Inhibition of apoptosis by Survivin predicts shorter survival rates in colorectal cancer. Cancer Res, 1998,58(22):5071-5074.
20. Thompson CB. Apoptosis in the pathogenesis and treatment of disease. J Science, 1995, 267(5203):1456-1462.
21. Ambrosini G, Adida C, Sirugo G, et al. Induction of apoptosis and inhibition of cell proliferation by Survivin gene targeting.J Biol Chem,1998,273(18):11177-11182.
22. Grossman D,Kim PJ,Schechner JS,et al.Inhibition of melanoma tumor growth in vivo by Survivin targeting. Proc Natl Acad Sci USA,2001,98(2):635-640.
23. Appleby SB,Rrstimaki A,Neilson K,et al.Structure of the human cyclo-oxygenase-2 gene.Biochem,1994,302(3):723-727.
24. Chen WS,Wei SJ,Liu JM,et al.Tumor invasiveness and liver metastasis of colon cancer cell correlated with cyclooxygenase-2(COX-2) expression and inhibited by a COX-2 seletive inhibitor,etodolac.Clin Cancer Res,2001,7(4):861-867.
25. Jodj T,Heese O,Nikas DC,et al.Expression of cyclooxygenase 2(COX-2) in human glioma and in vitro ingibition by a specific COX-2 inhibitor-NS-398.Cancer Res,2000, 60(17):4926-4931.
26. Tsujii M,Dubis RN.Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin eneoperoxide synthase 2.Cell,1995,83(3):493-501.
27. Sheng H,Shao J,Morrow JD,et al.Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells.Cancer Res,1998,58(2):362-366.
28. Higashi Y,Kanekura T.Kanzaki T.Enhanced expression of cyclooxygenase (COX-2) in human skin epidermal cancer cells:evidence for growth suppression by inhibiting COX-2 expression.Int J Cancer,2000,86(5):667-671.
29. Ma JH.Sui YF,Ye J,et al.Heat shock protein70/MAGE-3 fusion protein vaccinecan enhance cellular and humoral immune responses to MAGE-3 in vivo.Cancer Immunol Immunother,2005,54(9):907-914.
30. Nei TSZ,QiaoY,QianYWL. The role of heat shock protein in human breast cancer. J Chin Pathology,1998,17(1):34-38.
31. Wang XP,Liu GZ,Song AL,et al.Expression and significance of heat shock protein 70 and glucose-regulated protein 94 in human esophageal carcinoma.World J Gastroenterol,2005,11(3):429-432.
32. Isomoto H,Oka M,YanoY,et al.Expression of heat shock protein (Hsp)70 and Hsp40 in gastric cancer.Cancer Lett,2003,198(2):219-228.
33. Novoselov SS,Verbova MV,Vasileva EV,et al.Expression of Hsp70 and Hdjl chaperone proteins in human tumor cells.Vopr Onkol,2004,50(2):174-178.
34. Volm M,Koomagi R,Mattern J,et al.Protein expression profile of primary human squamous cell lung carcinomas indicative of the incidence of metastases.Clin Exp Metastasis,2002,19(5):385-390.
35．倪京满，杨小武，潘鑫复．抗癌药物放线菌素D及其新类似物体外DNA结合特性研究．兰州大学学报(自然科学版)，2002，38(3)：87-89．
36. Goldberg IH,Friedman PA.Antibiotics and nucleic acids. Annu Rev Biochem, 1971, 40:775-810.
37. Kiechle FL, Zhang X.Apoptosis:biochemical aspects and clinical implications.Clin Chim Acta,2002,326:27-45.
38. Chang TC,Tsai LC,Hung MW, et al.Effects of transcription and translation inhibitors on a human gastric carcinoma cell line. Potential role of Bcl-X(S) in apoptosis triggered by these inhibitors.Biochem Pharmacol.1997,53(7):969-977.
39. Ng CP, Bonavida B.X-linked inhibitor of apoptosis (XIAP) blocks Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis of prostate cancer cells in the presence of mitochondfial activation: sensitization by overexpression of second mitochondria-derived activator of caspase/direct lAP-binding protein with low pl(Smac/DIABLO). Mol Cancer Ther, 2002,1(12):1051-1058.
40. Rudin CM, Thompson CB. Apoptosis and disease: regulation and clinical relevance of programmed cell death. Annu Rev Med,1997,48:267-281.
41. Krieg A, Mahotka C, Krieg T, et al. Expression of different survivin variants in gastric carcinomas: first clues to a role of survivin-2B in tumour progression. Br J Cancer, 2002,86(5):737-743.
42. Newton R,Kuitert LM,Slater DM,et al.Cytokine induction of cytosolic phospholipase A2 and cyclooxygenase-2 mRNA is suppressed by glucocorticoids in human epithelial cells.Life Sci, 1997,60(1):67-78.
43. Kawaguchi Y, Sato C,Hasegawa T, et al.Intraarticular osteoid osteoma associated with synovitis:a possible role of cyclooxygenase-2 expression by osteoblasts in the nidus. Modern Pathology,2000,13(10):1086-1091.
44. Kiang JG, Kiang SC, Juang YT, et al. N(omega)-nitro-L-arginine inhibits inducible HSP-70 via Ca(2+), PKC,and PKA in human intestinal epithelial T84 cells. Am J Physiol Gastrointest Liver Physiol,2002,282(3):415-423.
45．黄培堂，俞炜源，陈添弥等译．PCR技术实验指南．北京：科学出版社，1998：88-94．
46. Carmichaei J, Mitchell JB, DeGraff WG, et al. Chemosensitivity testing of human lung cancer cell lines using the MTT assay. Br J Cancer, 1988,57(6):540-547.
47. Mosmann T.Papid colometric assay for cellular growth and survival,Application to prolife ration and cytotoxicity assays.J Immun Method,1983,65(1):55-64.
48. Wyllie AH, Morris RG, Smith AL, et al. Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol,1984,142(1):67-77.
49. Ratan RR, Murphy TH, Baraban JM. Oxidative stress induces apoptosis in embryonic cortical neurons. J Neurochem,1994,62(1):376-379.
50. Schwartz LM, Kosz L, Kay BK. Gene activation is required for developmentally programmed cell death. Proc Natl Acad Sci USA,1990,87(17):6594-6598.
51. Borner MM, Myers CE, Sartor O, et al. Drug-induced apoptosis is not necessarily dependent on macromolecular synthesis or proliferation in the p53-negative human prostate cancer cell line PC-3. Cancer Res,1995 55(10):2122-2128.
52. Martin SJ. Protein or RNA synthesis inhibition induces apoptosis of mature human CD4+ T cell blasts. Immunol Lett,1993,35(2):125-134.
53. Martin SJ. Apoptosis: suicide, execution or murder? Trends Cell Biol, 1993,3(5): 141-144.
54. Fernandes RS,Cotter TG.Activation of a calcium magnesium independent endonu-clease in human leukemic cell apoptosis. Anticancer Res,1993,13(5A):1253-1259.
55. Huschtacha LI,Teither TM,Auderson CE,et al.Identification of apoptotic and necrotic human leukemia cells by flow cytometry.Exp cell Res,1994,12(1):167-172.
56. Boise LH, Gonzalez-Garcia M, Postema CE, et al. bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death.Cell,1993,74(4):597-608.
57. Mercatante DR, Mohler JL, Kole R.Cellular response to an antisense-mediated shift of Bcl-x pre-mRNA splicing and antineoplastic agents. J Biol Chem,2 002,277(51): 49374-49382.
58. Beardsmore DM,Verbeke CS,Davies CL, et al.Apoptotic and proliferative indexes in esophageal cancer:predictors of respinse to neoadjuvant therapy apoptosis and proliferation in eaophageal cancer.J Gastriointestinal Surg,2003,7(1):77-87.
59. Ikeguchi M, Liu J, Kaibara N. Expression of survivin mRNA and protein in gastric cancer cell line (MKN-45) during cisplatin treatment. Apoptosis,2002,7(1):23-29.
60. Lu B, Mu Y, Cao C, et al. Survivin as a therapeutic target for radiation sensitization in lung cancer. Cancer Res,2004,64(8):2840-2845.
61. Sun Y, Tang XM,Half E,et al.Cyclooxygenase-2 overexpression reduces apoptotic suscdptibility by inhibiting the cytochromec dependent apoptotic pathwqy in human colon cancer cells.Cancer Res,2002,62(21):6323-6328.
62．王枫，于芳，曹瑞，等．HSP70 高表达对K562细胞化疗敏感性研究．中国公共卫生，2003，19(2)：141-143
63. Kampinga HH.Hyperthermia,thermotolerance and topoisomerase inhibitors.Bfint J Can,1995,72(2):333-338.
64. Oesterreich S,Weng CN,Qiu M,et al.The small heat shock proteins HSP27 is correlated with growth and drug resistance in human breast cancer cell lines.Cancer Res,1993,53(19): 4443-4448.
65. Krysan K, Merchant FH,Zhu L, et al.COX-2-cependent stabilization of survivin in non small cell lung cancer.FASEB J,2004,18(1):206-208.
66. Barnes N,Haywood P, Flint P, et al.Survivin expression in insitu and invasive breast cancer relates to COX-2 expression and DCIS recurrence.Br J Cancer,2006, 94(2): 253-258.
1. Schena M,Shalon D,Hcllcr R,ct al.Parallel human gcnome analysis:microarray based expression monitoring of 1000 genes.Proc Natl Acad Sci USA,1996,93(20): 10614 -10619.
2. Leethanakul C,Patcl V, Gillespic J,et al.Distinct pattern of expression of differentiation and growth-related genes in squamous cell cancinomas of the head and neck revealed by the use of laser capture microdisscction and cDNA arrays.Oncogcnc, 2000,19(28): 3220-3224.
3. Smid-Koopman E,Blok LJ,Chadha-Ajwani S,et al. Genc expression profiles of human endometrial cancer samples using a cDNA-expression array technique: assessment of an analysis method. Br J Cancer,2000,83(2):246-251.
4. Zhou Y, Gwadry FG, Reinhold WC,et al.Transcriptional regulation of mitotic genes by camptothecin-induced DNA damagc:microarray analysis of dose and time-dependent effects.Cancer Res,2002,62(2): 1688-1695.
5. Pastinen T, Raitio M,Lindroos K, et al. A system for specific, high throughput genotyping by allele specific primer extension on microarrays.Genome Res, 2000,10 (7):1031-1042.
6. Chee M,Yang R,Hubbell E,et al.Accessing genetic information with high-density DNA arrays.Science, 1996,274:610-614.
7．陈亚利，陆祖宏．微芯片—生命科学领域的新工具．生物化学与生物物理进展，1998，25(6)：517-521．
8. Schena M,Shalon D,Dais RW, Brow PO.Quantitative monitoring of gene expression patterns with a complementary DNA microarray.Science,1995,270:467-470.
9. Gresham D,Rudeffer DM,Pratt SC, et al.Genome-wide detection of polymorphisms at nucleotide resolution with asingle DNA microarray. Science, 2006,311(5769): 1932- 1936.
10. Alcorta DA,Prakash K, Waga I,et al.Future molecular approaches to the diagnosis and treatment of glomerular disease.Semin Nephrol,2000,20(1):20-31.
11. Tennis M,Krishnan S,Bonner M,et al.p53 mutation analysis in breast tumors by a DNA microarray method.Cancer Epidemiol Biomarkers Prey,2006,15(1):80-85.
12. Pastore A,Carinci F, Pelucchi S.Genetic expression profiling of parotid neoplasms by cDNA microarrays.Acta Otorhinolaryngol Ital,2005,25(3):153-160.
13. Shroi DC,Teng S,Robinson G, et al.In vivo gene expression profile analysis of human breast cancer progression.Cancer Res,1999,59(22):5656-5661.
14. Anderson KM,Alrefar WA, Anderson CA,et al.A response of Panc-1 cells to cis-platinum, assessed with a cDNA array. Anticancer Res,2002, 22(1A): 75-81.
15. Freemantle SJ, Kerley JS, Olsen SL, et al. Developmentally-related candidate retinoic acid target genes regulated early during neuronal differentiation of human embryonal carcinoma. Oncogene,2002,21:2880-2889.
16. Sawids GP, Sherman-Baust CA, Beeker KG, et al.Development of a highly specialized cDNA array for the study and diagnosis of epithelial ovarian cancer. Cancer Res, 2002, 62(10):2923-2928.
17. Rhee CH,Hess K,Jabbur J,et al.cDNA expression array reveals heterogeneous gene expression profiles in three glioblastoma cell lines.Oncogene,1999,18(17):2711-2717.
18. Wang K, Gan I,Jefferry E, et al.Monitoring gene expression profile change in ovarian carcinomas using cDNA microarray. Gene, 1999,229(1 - 2): 101 - 108.
19. Xie L, Xul H,He Z, et al.ldentification of differentially expressed genes in nasopharyngeal carcinoma by means of the Atlas human cancer cDNA expression array.J Cancer Res Clin Oncol,2000,126(7):400 406.
20. Lee JS,Thorgeirsson SS.Functional and genomic implications of global gene expression profiles in cell lines from human hepatocellular cancer. Hepatology, 2002, 35(5):1134 1143.
21. Chong VZ,Young LT, Mishra RK.cDNA array reveale differential gene expression following chronic neuroleptic administration: Implications of synapsin Ⅱ in haloperidol treatment. J Neurochem,2002,82(6): 1533-1539.
22．孙德利，舒琦瑾．基因表达谱——中医药功能基因组学研究的思考．浙江中医学院学报，2002，26(1)：5-9．
23. Bortoli S,Renault V, Eveno E,et al.Gene expression profiling of human satellite cell during muscular aging using cDNA arrays.Gene,2003,321(2): 145-154.
24. Courtney S,Mossoba ME,Hammack TS,et al.Using PCR amplification to increase the confidence level of Salmonella typhimurium DNA microarray chip hybridization. Mol Cell Probes,2006,20(3): 163-171.
25. Galamb O,Molnar B,Tulassay Z.DNA chips for gene expression analysis and their application in diagnostics.Orv Hetil,2003,144(1):21-27.
26．王维民，刘延庆．基因芯片在肿瘤临床中的应用进展．肿瘤，2006，26(9)：870-872．
27. Ren CP, Lin WD,He ZW, et al.Differentially expressed gene profile of hCR2 transfected mouse cells before and after EBV infection and TPA treatment. Acta Biochim Biophys Sin,2001,33(1):105-111.
28. Hayase T, Yamamoto Y, Yamamoto K, et al.Microarray profile analysis of toxic cocaine induced alterations in the expression of mouse brain gene sequences:a possible 'protective' effect of buprenorphine.J Appl Toxicol,2004,24(1):15-20.
29. Sato H.Ishida S,Toda K,et al.New approaches to mechanism a nalysis for drug discovery using DNA microarray data combined with KeyMolnet. Cun Drug Discov Technol,2005,2(2):89-98.
30. Guzey C,Spigset O.Genotyping of drug targets:a method to predict adverse drug reaction?DrugSaf,2002,25(8):553-560.
31. Frye JG.Jesse T,Long F,et al.DNA microarray detection of antimicrobial resistance genes in diverse bacteria.Int J Antimicrob Agents,2006,27(2):138-151.
32. Stells H.Mechanisms and gene of cellular suicide.Science,1995,267(5023):1445-1449.
33. Chen KF, Lai YY, Sun HS, et al.Transcriptional repression of human cad gene by hypoxia inducible factor-1 alpha. Nucleic Acids Res,2005,33(16):5190-5198.
34. Yang D,Nakao M,Shichijo S,et al.Identification of a gene coding for a protein possessing shared tumor epitopes capable of inducing HLA-A24-restricted cytotoxic T lymphocytes in cancer patients.Cancer Res,1999,59(16):4056-4063.
35. Sasatomi T,Suefuji Y,Matsunaga K,et al.Expression of tumor rejection antigens in colorectal carcinomas.Cancer,2002,94(6): 1636-1641.
36. Tsuda N,Murayama K,Ishida H,et al.Expression of a newly defined tumor- rejection antigen SART3 in musculoskeletal tumors and induction of HLA class I-restricted cytotoxic T lymphocytes by SART3 derived peptides.J Orthop Res,2001,19(3): 346-351.
37. Stossi F,Barnett DH,Frasor J,et al.Transcriptional profiling of estrogen- regulated gene expression via estrogen receptor (ER) ERα or ERβ in human osteosarcoma cells: distinct and common target genes for these receptors. Endocrinology, 2003,145(7): 3473-3486.
38. Xia L,Nordman T,Olsson J,et al .The mammalia cytosolic selenoenzyme thioredoxin reductase reduces ubiquinone.A novel mechanism for defense against oxidative stress. J Biol Chem,2003,278(4):2141-2146.
39. Anestal K, Arner ES.Rapid induction of cell death by selenium compromised thioredoxin reductase 1 but not by the fully active enzyme containing selenocysteine. J Biol Chem,2003,278(18): 15966-15972.
40. Gromer S,Urig S,Becker K. The thioredoxin system--from science to clinic.Med Res Rev, 2004,24(1):40-89.
41．纪冬，成军，郭江，等．乙型肝炎病毒X蛋白上调硫氧还蛋白还原酶1基因表达的研究．胃肠病学和肝病学杂志，2005，14(1)：18-22．
42. Tamura T, Stadtman TC.A new selenoprotein from human lung adenocarcinoma cells: purification, properties, and thioredoxin reductase activity. Proc Natl Acad Sci USA,1996,93 (3): 1006-1011.
43. Gladyshev VN,Jeang KT, Stadtman TC.Selenocysteine, identified as the penultimate C-terminal residue in human T-cell thioredoxin reductase, corresponds to TGA in the human placental gene. Proc Natl Acad Sci USA,1996,93(12):6146-6151.
44. Berggren M,Gallegos A, Gasdaska JR,et al.Thioredoxin and thioredoxin reductase gene expression in human tumors and cell lines, and the effects of serum stimulation and hypoxia. Anticancer Res, 1996,16 (6B):3459-3466.
45. Kahlos K, Soini Y, Saily M,et al.Up-regulation of thioredoxin and thioredoxin reductase in human malignant pleural mesothelioma.lnt J Cancer,2001,95(3): 198-204.
46. Nilsson J, Soderberg O,Nilsson K, et al.Thioredoxin prolongs survival of B-type chronic lymphocytic leukemia cells.Blood, 2000,95(4): 1420-1426.
47. Chen Yan,Cai J,Murphy TJ,et al.Overexpressed human mitochondrial thioredoxin confers resistance to oxidant-induced apoptosis in human osteosarcoma cells.J Biol Chem, 2002,277(36):33242-33248.
48. Ungerstedt JS, Sowa Y, Xu WS, et al.Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors. Proc Natl Acad Sci USA,2005, 102(3):673-678.
49. Renschler MF. The emerging role of reactive oxygen species in cancer therapy. Eur J Cancer,2004,40(13):1934-1940.
50. Davis W, Jr, Ronai Z,et al.Tew cellular thiols and reactive oxygen species in drug-induced apoptosis. J Pharmacol Exp Ther.Vol, 2001,296(1):1-6.
51. Hulmej T.Coppock EA,Felipe A,et al.Oxygen sensitivity of cloned voltage-gated K~+ channels expressed in the pulmonary vasculature.CircRes,1999,85(6):489-497.
52. Semenza GL.HIF-l:mediator of physiological and pathophysiological responsis to hypoxia.J Apply Physiol,2000,88(4):1474-1480.
53. Yan L,Figueroa DJ,Austin CP,et al. Expression of voltage-gated potassium channels in human and rhesus pancreatic islets.Diabetes,2004,53:597-607.
54. Hall MC,Matson SW.Helicase motifs:the engine that powers DNA unwinding.MoI Microbiol,1999,24(5):867-877.
55. Silvermen E,Edwalds GG,Iin RJ.DexD/H box protein and their partners:helping RNA helicases unwind.Gene,2003,312:l-16.
56. Henning D, So RB, Jin R,et al. Silencing of RNA helicase II/Gualpha inhibits mammalian ribosomal RNA production.J Biol Chem,2003,278(52):52307-52414.
57. Cho-Chung YS,Pepe S,Clair T,et al.cAMP- dependent protein kinase role in normal and malignant growth.Crit Rev Oncol Hematol,1995,21(l-3):33-61.
58. Miller WR,Watson DM,Jack W,et al.Tumor cyclic AMP binding proteins:an independent prognostic factor for disease recurrence and survival in breast cancer. Breast Cancer Res Treat,1993,26(1):89-94.
59. Ciardiello F,Damiano V,Bianco C,et al.Cooperative antiproliferative effects 8-C1-cAMP and 528 antiepidermal growth factor receptorm onoclonal antibody on human cancer cells.Clin Cancer Res,1995,l(2):161-167.
60. Murai T.Leucine aminopeptidase(LAP).Rinsho Byori,2001,116(suppl):110-116.
61. Kawai M,Hara Y,Miyazato I,et al.Aberrantly truncated isoform of serum CD13 in a family with high serum aminopeptidase N(CD13) activity.Clin Chem,2001, 47(2): 223-230.
62. Varshavsky A.The N-end rule:functions,mysteries uses. Proc Natl Acad Sci USA, 1996, 93(22): 12142-12149.
63. Qu CK.Role of the SHP-2 tyrosine phosphatase in cytokine-induced signaling and cellular response.Biochim Biophys Acta,2002,1592(3):297-301.
64. Carlesso N,Frank DA,Griffin JD.Tyrosyl phosphorylation and DNA binding activity of signal tuansducers and activators of transcription (STAT) proteins in hemetopoietic cell lines transformed by Bcr/Abl. Exp Med,1996,183:811-820.
65. Neel BG,Gu H,Pao L.The'Shp'ing news:SH2 domain-containing tyrosine phospha-tases tases in cell signaling.Trends Biochem Sci,2003,28(6):284-293.
66. Radke I,Gotte M,Kersting C,et al.Expression and prognostic impact of the protein tyrosine phosphatases PRL-1, PRL-2, and PRL-3 in breast cancer.Br J Cancer,2006, 95(3):347-354..
67. Sun JP,Wang WQ,Yang H,et al. Structure and biochemical properties of PRL-1, a phosphatase implicated in cell growth, differentiation, and tumor invasion. Biochemistry, 2005,44(36):12009-12021.
68. Veale M,Raab M,Li Z,et al.Novel isoform of lymphoid adaptor FYN-T-binding protein (FYB-130) interacts with SLP-76 and up-regulates interleukin 2 production.J Biol Chem, 1999,274(40):28427-28435.
69. Duke-Cohan JS,Kang H,Liu H,et al.Regulation and function of SKAP-55 non-canonical motif binding to the SH3c domain of adhesion and degranulation-promoting adaptor protein.J Biol Chem, 2006,281(19):13743-13750.
70. Kaur M,Pop M,Shi D,et al. hHR23B is required for genotoxic-specific activation of p53 and apoptosis. Oncogene,2007,26(8): 1231-1237.
71. Hsieh HC,Hsieh YH,Huang YH,et al.HHR23A, a human homolog of Saccharomyces cerevisiae Rad23, regulates xeroderma pigmentosum C protein and is required for nucleotide excision repair. Biochem Biophys Res Commun,2005,335(1): 181-187.
72. Erez A,Perelman M,Hewitt SM,et al.Sil overexpression in lung cancer characterizes tumors with increased mitotic activity. Oncogene,2004,23(31):5371-5377.
73. Favre C,Carnovale CE,Monti JA.Inhibition by interferona-2b of rat liver regeneration: effect on ornithine decarboxylase and total protein synthesis.Biochemical Pharmacology, 2001,61(12):1587-1593.
74. Mimorl K, Mori M,Shiraishi T,et al.Analysis of ornithine decarboxylase messenger ribonucleic acid expression in colorectal carcinoma.Dis Colon Rectum, 1997, 40 (9): 1095-1100.
75. Sahu S,Khadeer M,Bai G,et al.Over expression of the ZIPl zine transporter induces an osteogenic phenotype in mesenchymal stem cells.Bone,2006,38(2):181-198.
76. Taylor KM.LIV1 breast cancer protein belongs to new family of histidine rich membrane proteins with potential to control intracellular Zn~(2+) homeostasis.IUBMB Life,2000,49(4):249-253.
77. Kasper G,Weiser AA,Rump A,et al.Expression levels of the putative zinc transporter LIV-1 are associated with a better outcome of breast cancer patients.Int J Cancer,2005, 117(6):961-973.
78. Chen TC,Holick MF,Lokeshwar BL,et al.Evaluation of vitamin D analogs as therapeutic agents for prostate cancer.Recent Results Cancer Res, 2003,164:273-288.
79. Chrng JW,Jeon JH,Yoon SR,et al.Vitamin D3 upregulated protein (VDUP1) is a regulator for redox signaling and stress-mediated diseases.J Dermatology, 2006, 33 (10):662-669.
80. Minn AH,Hafele C,Shalev A. Thioredoxin-interacting protein is stimulated by glucose through a carbohydrate response element and induces beta-cell apoptosis. Endocrinology,2005,146(5):2397-2405.
81. Goldberg SF,Miele ME,Hatta N,et al.Melanoma metastasis suppression by chromosome 6 evidence for a pathway regulated by CRSP3 and TXNIP.Cancer Res,2003,63:432-440.
82. Huang L,Pardee AB.Suberoylanilide hydroxamic acid as a potential therapeutic agent for human breast cancer treatment.Mol MED,2000,6(10):849-866.
83. Prudencio J,Adutsu N,Benlimame N,et al.Action of low calcemicl alpha ,25-dihydroxyvitamin D3 analogue EB1089 in head and necd squamous cell carcinoma.J Natl Cancer,2001,93(10):745-753.
84. Lin R,Wang TT,Miller WH,et al.Inhibition of F-box protein p45~(SKP2) expression and stabilization of cyclin-dependent kinase inhibitor p27~(KIP1) in vitamin D analog-treated cancer cells.Endocrinology,2003,144(3):749-753.
85. Tartaglia J,Bonnet MC,Berinstein N,et al.Therapeutic vaccines against melanoma and colorectal cancer.Vaccine,2001,19(17-19):2571-2575.
86. Juretic A,Spagnoli GC,Schultz TE,et al.Cancer/testis tumour-associated antigens: immunohistochemical detection with monoclonal antibodies.Lancet Oncol,2003, 4(2): 104-109.
87. Breitling R, Laubner D, Clizbe D,et al. Isopentenyl-diphosphate isomerases in human and mouse: evolutionary analysis of a mammalian gene duplication.J Mol Evol,2003, 57(3):282-291.
88. Tabuchi Y,Ando H,Tadasaki I,et al.Identification of genes responsive to low intensity pulsed ultrasound in a human leukemia cell line Molt-4.Cancer Lett,2007, 246 (1-2): 149-156.
89. Goldberg J.Structural basis for activation of ARF GTPase: mechanisms of guanine nucleotide exchange and GTP-myristoyl switching.Cell,1998,95(2):237-248.
90. Min DS, Kwon TK, Park WS et al. Neoplastic transformation and tumorigenesis associated with overexpression of phospholipase D isozymes in cultured murine fibroblasts.Carcinogenesis,2001,22(10):1641-1647.
91. Takahashi Y,Nagata T,Ishii Y,et al.Up-regulation of vitamin D3 up-regulated protein 1 gene in response to 5-fluorouracil in colon carcinoma SW620.Oncol Rep,2002, 9(1):75-79.
1. Chen JQ, Zhan WH, He YL, et al. Expression of heparanase gene, CD44v6, MMP-7 and nm23 protein and their relationship with the invasion and metastasis of gastric carcinomas. World J Gastroenterol,2004,10(6):776-782.
2. Nocito A, Kononen J,Kallioniemi OP, et al.Tissue microarrays (TMAs) for high-throughput molecular pathology research.Int J Cancer,2001,94(1):l-5.
3．周小鸽，张劲松，张小平，等．组织芯片．中华病理学杂志，2002，31(1)：70-72．
4. Battifora H. The multitumor (sausage) tissue block: novel method for immunohistochemical antibody testing. Lab Invest,1986,55:244-248.
5. Kononen J,Bubendorf L, Kalliviemi A, et al.Tissue microarrays for high-through put molecular profiling of tumor specimens.Nat Med,1998,4(7):844-847.
6. Manley S,Mucci NR, de Matzo AM,et al.Relational database structure to manage high-denaily tissue microarray data and images for pathology stadies focusing on clinical outcome:The prostate specialized program of research excellence model.Am J Pathol,2001,159(3):837-843.
7. Mahotka C,Wenzel M,Springer E, et al.Survivin-deltaEx3 and survivin-2B:two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties. Cancer Res,1999,59(24):6097-6102.
8. lkehara M, Oshita F, Kameda Y, et al. Expression of survivin correlated with vessel invasion is a marker of poor prognosis in small adenocarcinoma of the lung.Oncol Rep, 2002,9(4):835-838.
9. Tanaka K, Iwamoto S, Gon G, et al. Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res,2000,6(1): 127-134.
10. Wakana Y, Kasuya K, Katayanagi S, et al. Effect of survivin on cell proliferation and apoptosis in gastric cancer. Oncol Rep,2002,9(6):1213-1218.
11. Kato J, Kuwabara Y, Mitani M, et al. Expression of Survivin in esophageal cancer: correlation with the prognosis and response to chemotherapy. Int J Cancer, 2001, 95(2):92-95.
12. Kallakury BV.Shechan CE,Ambros RA,et al.The progncsitid siginificance of P34cdc2 and cyclinDl protein expression in prostate adenocacinoma.Cancer,1997, 80(4): 753-763.
13. Shin S,Sung BJ,Cho YS,et al.An anti-apoptotic protein human surviving is a direct inhibitor of caspase 3 and caspase 7.Biochemistry,2001,40(4):1117-1123.
14. Chen J, Wu W, Tahir SK, et al. Down-regulation of Survivin by antisense oligonucleotides increases apoptosis, inhibits cytokinesis and anchorage-independent growth. Neoplasia, 2000,2(3):235-241.
15. Sarela AI, Macadam RC, Farmery SM, et al. Expression of the antiapoptosis gene, survivin,predicts death from recurrent colorectal carcinoma. Gut, 2000,46(5):645-650.
16. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, Survivin, expressed in cancer and lymphoma. Nat Med,1997,3(8):917～921.
17. Tsuburaya A, Noguchi Y, Yoshikawa T, et al. An anti-apoptosis gene, Survivin and telomerase expression in gastric cancer. Hepatogastroenterology, 2002, 49(46): 1150-1152.
18. Miyachi K, Sasaki K, Onodera S, et al. Correlation between Survivin mRNA expression and lymph node metastasis in gastric cancer. Gastric Cancer, 2003,6(4): 217-224.
19. Chen WS,Wei SJ,Liu JM,et al.Tumor invasiveness and liver metastasis of colon cancer cell correlated with cyclooxygenase-2(COX-2) expression and inhibited by a COX-2 seletive inhibitor,etodolac.Clin Cancer Res,2001,7(4):861-867.
20. Kinoshita T,Tadahashi Y,Sakashita T,et al.Growth stimulation and induction of epidermal growth factor receptor by overexpression of cyclooxygenases land 2 in human colon carcinoma cells.Biochim Biophys Acta,1999,1438(1):120-130.
21. Tsujii M,Kawano S,DuBois RN.Cycollxygenase-2 expression in human colon cancer cells increases metastatic potential.Proc Natl Acad Sci USA,1997,94(7):3336-3340.
22. O'Mahony CA,Beauchamp RD,Albo D,et al.Cyclooxygenase-2 alters transforming growth factor-beta 1 response during intestinal tumorigenesis.Surgery, 1999,126(2): 364-370.
23. Tucker ON, Dannenberg AJ, Yang EK,et al. Cyclooxygenase2 expression is up-regulated in human pancereatic cancer. Cancer Res,1999,59(5):987-990.
24. Liang JT, Huang KC, Jeng YM,et al. Microvessel density, cyclo-oxygenase 2 expression, K-ras mutation and p53 overexpression in colonic cancer. Br J Surg, 2004,91(3):355-361.
25. Xue YW,Zhang QF,Zhu ZB,et al.Expression of cyclooxygenase-2 and clinico-pathologic features in human gastric adenocarcinoma.Would J Gastroenterol, 2003,9: 250-253.
26. Ohno R, Yoshinaga K, Fujita T, et al. Depth of invasion parallels increased cyclooxygenase-2 levels in patients with gastric carcinoma.Cancer, 2001,91(10): 1876-1881.
27. Ellis RJ. Molecular chaperones: plugging the transportgap.Nature,2003,421(6925): 801- 802.
28. Zhang SHL,Wei SO,Li ST.Immunohistochemical study of heat shock protein 70 in mose endometrium during carlyregnancy.J Anat,2002,25(1):21-24.
29. Lauten M, Beger C, Gerdes K, et al. Expression of heat-shock protein 90 in glucocorticoid- sensitive and -resistant childhood acute lymphoblastic leukaemia. Leukemia,2003,17(8): 1551-1556.
30. O'Neill PA, Shaaban AM, West CR, et al.Increased risk of malignant progression in benign proliferating breast lesions defined by expression of heat shock protein 27. Br J Cancer, 2004,90(1):182-188.
31. Uozaki H, Ishida T, Kakiuchi C, et al. Machinami R. Expression of heat shock proteins in osteosarcoma and its relationship to prognosis. Pathol Res Pract,2000,196(10): 665-673.
32. Elpek GO, Karaveli S, Simsek T,et al. Expression of heat-shock proteins hsp27, hsp70 and hsp90 in malignant epithelial tumour of the ovaries. APMIS,2003,111(4):523-530.
33. Lambot MA, Peny MO, Fayt I, et al.Overexpression of 27-kDa heat shock protein relates to poor histological differentiation in human oesophageal squamous cell carcinoma. Histopathology, 2000,36(4):326-330.
34. Zuo DS, Dai J, Bo AH, et al. Significance of expression of heat shock protein90alpha in human gastric cancer. World J Gastroenterol, 2003,9(11):2616-2618.
35. Torronteguy C, Frasson A, Zerwes F, et al. Inducible heat shock protein 70 expression as a potential predictive marker of metastasis in breast tumors.Cell Stress Chaperones, 2006,11(1): 34-43.
36. Hwang TS, Han HS, Choi HK, et al. Differential, stage-dependent expression of Hsp70, Hsp110 and Bcl-2 in colorectal cancer. J Gastroenterol Hepatol ,2003,18(6): 690-700.
37. Noguchi T, Wada S, Takeno S, et al. Lymph node metastasis could be predicted by evaluation of macrophage infiltration and hsp70 expression in superficial carcinoma of the esophagus. Oncol Rep, 2003,10(5):1161-1164.
38. Cappello F, David S, Rappa F,et al. The expression of HSP60 and HSP10 in large bowel carcinomas with lymph node metastase. BMC Cancer,2005,5:139.