蜈蚣水提取物对胆管癌细胞株QBC939体内外抗肿瘤作用的实验研究及机制探讨
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摘要
目的：
1.用光学显微镜、MTT、细胞集落试验及透射电镜等不同方法,观测不同浓度的蜈蚣水提取物对人胆管癌细胞株QBC939体外抑制作用。计算其IC50值。
2.建立胆管癌细胞株QBC939裸鼠皮下瘤模型,用10g/kg蜈蚣水提取物灌胃处理胆管癌细胞株QBC939移植瘤裸鼠,比较治疗组及对照组皮下瘤模生长情况。
3.取治疗组及对照组人胆管癌细胞株QBC939裸鼠皮下移植瘤瘤体行蛋白质组学分析,寻找差异性蛋白。
4.根据蛋白质组学结果,取胆管癌细胞株QBC939裸鼠皮下瘤体行BCL-2及BAX的半定量RT-PCR及Western blot分析,探讨蜈蚣水提取物促进胆管癌细胞凋亡的可能机制。
方法：
1.光镜观测蜈蚣水提取物对人胆管癌细胞株QBC939作用后的形态学改变及集落变化,计算其IC50值。透射电镜观测IC50值蜈蚣水提取物处理人胆管癌细胞株细胞QBC93948小时,肿瘤细胞结构改变情况。
2.建立人胆管癌细胞QBC939裸鼠皮下移植瘤模型,移植瘤术后第12天,采用10g/kg蜈蚣水提取物灌胃处理移植瘤裸鼠,每日一次,共21次。观察记录肿瘤变化情况绘制生长曲线图。移植瘤术后第35天解剖移植瘤裸鼠,观测皮下移植瘤体积、重量及H.E染色情况。
3.用蛋白质组学技术检测蜈蚣水提取物处理前后两组人胆管癌细胞QBC939皮下移植瘤蛋白表达的差异。
4.上述两组人胆管癌细胞QBC939皮下移植瘤的标本行RT-PCR及Western blot检测Bcl-2及Bax的变化情况。探讨蜈蚣水提取物促进胆管癌细胞凋亡的可能机制。
结果：
1.蜈蚣水提取物有抑制胆管癌QBC939细胞生长的作用,随着蜈蚣水提取物浓度逐渐增加,其抑瘤作用递增。其IC50值为12.5mg/ml.蜈蚣水提取物能抑制人胆管癌细胞株QBC939细胞集落的形成。电镜观察用半数抑制剂量的蜈蚣水提取物处理人QBC939胆管癌细胞48h后,可见明显的凋亡小体。
2.成功建立人胆管癌细胞株QBC939裸鼠移植瘤动物模型；与对照组相比,10 g/kg蜈蚣水提取物灌胃对裸鼠QBC939胆管癌皮下移植瘤具有抑制作用；H.E染色可见实验组肿瘤细胞可见空泡化及大量核固缩,而对照组少见。
3.蛋白质组学检测显示,对比QBC939皮下移植瘤细胞38个差异性蛋白。有27个下调,有11个上调, CK8、CK18及Bcl-2相关蛋白表达下调,Galectin-1和Galectin-7表达上调。
4.RT-PCR及Western blot检测实验组的Bax上调而Bcl-2下调。
结论：
1.蜈蚣水提取物有抑制胆管癌QBC939细胞生长的作用,随着蜈蚣水提取物浓度逐渐增加,抑瘤作用递增,其48小时IC50值为12.5mg/ml。
2：成功建立人胆管癌细胞株QBC939裸鼠移植瘤动物模型,10g/kg蜈蚣水提取物对裸鼠QBC939胆管癌皮下移植瘤具有抑制作用。
3：蜈蚣水提取物的治疗引起胆管癌QBC939皮下移植瘤细胞蛋白质组学的38个差异。CK8、CK18及Bcl-2相关蛋白表达下调,Galectin-1和Galectin-7表达上调。
4：蜈蚣水提取物对胆管癌QBC939的抑制作用,可能是通过上调Bax及下调Bcl-2途径引起胆管癌细胞的凋亡来实现的。
Objective:
1.To explore the inhibitory effects of Centipede Aqueous Extract on cholangiocarcinoma Cell lines QBC939 in vitro.
2. To establish the nude mice subcutaneous tumors model of QBC939 cells, The treatment groups were fed with the Centipede Aqueous Extract on the concentration of lOg/kg while the control group were fed with the Saline water. The growth of the two groups were recorded in detail.
3. To analysis the proteomics difference between the treatment and the control groups
4.To study the possible antitumor mechanisms of Centipede Aqueous Extract on cholangiocarcinoma cell line QBC939 subcutaneous tumors by molecular biology technology.
Methods:
1. The morphological and colony changes of cholangiocarcinoma cell line QBC939 were observed in different concentration of Centipede Aqueous Extract by light microscopy,and the changes of the cell structure were studied by transmission electron microscopy.
2. The model the nude mice subcutaneous tumors of human cholangiocarcinoma cell QBC939 were established.12 days after Subcutaneous transplantation, the treatment group nudes were fed with the Centipede Aqueous Extract on the concentration of lOg/kg while the control group were fed with the Saline water. The changes of tumor size between the treatment and control groups were recorded in details.35 days after subcutaneous transplantation, all the nude mice were anatomized and subcutaneous tumors were observed by H.E staining.
3.The protein expression differences of Cholangiocarcinoma QBC939 cell subcutaneous tumors were detected by proteomics.
4.To explore the mRNA and protein levels of Bcl-2 and Bax in Cholangiocarcinoma QBC939 cell subcutaneous tumors and its possible mechanism. the samples of the experimental and control groups were detected by RT-PCR and Western blot.
Results:
1. The growth of cholangiocarcinoma cells QBC939 could be inhibited by Centipede Aqueous Extract. With gradually increasing concentration its anti-tumor effect was also enhanced too. Its IC50 value of 48 hours was 12.5mg/ml. and Centipede Aqueous Extract could also inhibit the colony-forming of cholangiocarcinoma cell line QBC939 cells. Electron microscopy showed that the apoptosis bodies could be seen clearly in Centipede Aqueous Extract treatment cholangiocarcinoma QBC939 cells by the concentration of 12.5mg/ml after 48h.
2. Successfully established were the nude mice subcutaneous tumors model of Cholangiocarcinoma QBC939 cells. After fed with of Centipede Aqueous Extract on the concentration of 10g/kg, Obvious different Growth rates were observed between the treatment group and control groups; Plenty of vacuolization and karyopyknosis cells were seen in experimental group by HE staining,rarely in the control group.
3. Compared to 38 proteins differentially expressed significantly in Cholangiocarcinoma QBC939 subcutaneous tumors tissues, among which 27 ribosomal protein genes were down-regulated significantly, while 11 ribosomal protein genes were up-regulated. CK8、CK18及Bcl-2 were down-regulated while Galectin-1 and Galectin-7 genes were down-regulated.
4. The result of RT-PCR and Western blot showed that the mRNA and protein levels of Bax were increased and those of Bcl-2 were declined in the experimental groups compared to the control groups
Conclusion:
1. Cholangiocarcinoma QBC939 cells could be inhibited by Centipede Aqueous Extract in vitro. With gradually increasing concentration its anti-tumor effect was also enhanced too. Its IC50 value was 12.5mg/ml.
2. Successfully established were the nude mice subcutaneous tumors model of Cholangiocarcinoma QBC939 cells. Centipede Aqueous Extract with the concentration of lOg/kg might have anti-tumor effect on the nude mice subcutaneous tumors.
3. There were 38 proteins differentially expressed significantly in Cholangiocarcinoma QBC939 cells subcutaneous tumors tissues, CK8、CK18 and Bcl-2 were down-regulated while Galectin-1 and Galectin-7 genes were down-regulated.
4. The apoptosis mechanism of treatment group Cholangiocarcinoma cells might be that up-regulated Bax and down-regulated Bcl-2 by Centipede Aqueous Extract.
1.用光学显微镜、MTT、细胞集落试验及透射电镜等不同方法,观测不同浓度的蜈蚣水提取物对人胆管癌细胞株QBC939体外抑制作用。计算其IC50值。
2.建立胆管癌细胞株QBC939裸鼠皮下瘤模型,用10g/kg蜈蚣水提取物灌胃处理胆管癌细胞株QBC939移植瘤裸鼠,比较治疗组及对照组皮下瘤模生长情况。
3.取治疗组及对照组人胆管癌细胞株QBC939裸鼠皮下移植瘤瘤体行蛋白质组学分析,寻找差异性蛋白。
4.根据蛋白质组学结果,取胆管癌细胞株QBC939裸鼠皮下瘤体行BCL-2及BAX的半定量RT-PCR及Western blot分析,探讨蜈蚣水提取物促进胆管癌细胞凋亡的可能机制。
方法：
1.光镜观测蜈蚣水提取物对人胆管癌细胞株QBC939作用后的形态学改变及集落变化,计算其IC50值。透射电镜观测IC50值蜈蚣水提取物处理人胆管癌细胞株细胞QBC93948小时,肿瘤细胞结构改变情况。
2.建立人胆管癌细胞QBC939裸鼠皮下移植瘤模型,移植瘤术后第12天,采用10g/kg蜈蚣水提取物灌胃处理移植瘤裸鼠,每日一次,共21次。观察记录肿瘤变化情况绘制生长曲线图。移植瘤术后第35天解剖移植瘤裸鼠,观测皮下移植瘤体积、重量及H.E染色情况。
3.用蛋白质组学技术检测蜈蚣水提取物处理前后两组人胆管癌细胞QBC939皮下移植瘤蛋白表达的差异。
4.上述两组人胆管癌细胞QBC939皮下移植瘤的标本行RT-PCR及Western blot检测Bcl-2及Bax的变化情况。探讨蜈蚣水提取物促进胆管癌细胞凋亡的可能机制。
结果：
1.蜈蚣水提取物有抑制胆管癌QBC939细胞生长的作用,随着蜈蚣水提取物浓度逐渐增加,其抑瘤作用递增。其IC50值为12.5mg/ml.蜈蚣水提取物能抑制人胆管癌细胞株QBC939细胞集落的形成。电镜观察用半数抑制剂量的蜈蚣水提取物处理人QBC939胆管癌细胞48h后,可见明显的凋亡小体。
2.成功建立人胆管癌细胞株QBC939裸鼠移植瘤动物模型；与对照组相比,10 g/kg蜈蚣水提取物灌胃对裸鼠QBC939胆管癌皮下移植瘤具有抑制作用；H.E染色可见实验组肿瘤细胞可见空泡化及大量核固缩,而对照组少见。
3.蛋白质组学检测显示,对比QBC939皮下移植瘤细胞38个差异性蛋白。有27个下调,有11个上调, CK8、CK18及Bcl-2相关蛋白表达下调,Galectin-1和Galectin-7表达上调。
4.RT-PCR及Western blot检测实验组的Bax上调而Bcl-2下调。
结论：
1.蜈蚣水提取物有抑制胆管癌QBC939细胞生长的作用,随着蜈蚣水提取物浓度逐渐增加,抑瘤作用递增,其48小时IC50值为12.5mg/ml。
2：成功建立人胆管癌细胞株QBC939裸鼠移植瘤动物模型,10g/kg蜈蚣水提取物对裸鼠QBC939胆管癌皮下移植瘤具有抑制作用。
3：蜈蚣水提取物的治疗引起胆管癌QBC939皮下移植瘤细胞蛋白质组学的38个差异。CK8、CK18及Bcl-2相关蛋白表达下调,Galectin-1和Galectin-7表达上调。
4：蜈蚣水提取物对胆管癌QBC939的抑制作用,可能是通过上调Bax及下调Bcl-2途径引起胆管癌细胞的凋亡来实现的。
Objective:
1.To explore the inhibitory effects of Centipede Aqueous Extract on cholangiocarcinoma Cell lines QBC939 in vitro.
2. To establish the nude mice subcutaneous tumors model of QBC939 cells, The treatment groups were fed with the Centipede Aqueous Extract on the concentration of lOg/kg while the control group were fed with the Saline water. The growth of the two groups were recorded in detail.
3. To analysis the proteomics difference between the treatment and the control groups
4.To study the possible antitumor mechanisms of Centipede Aqueous Extract on cholangiocarcinoma cell line QBC939 subcutaneous tumors by molecular biology technology.
Methods:
1. The morphological and colony changes of cholangiocarcinoma cell line QBC939 were observed in different concentration of Centipede Aqueous Extract by light microscopy,and the changes of the cell structure were studied by transmission electron microscopy.
2. The model the nude mice subcutaneous tumors of human cholangiocarcinoma cell QBC939 were established.12 days after Subcutaneous transplantation, the treatment group nudes were fed with the Centipede Aqueous Extract on the concentration of lOg/kg while the control group were fed with the Saline water. The changes of tumor size between the treatment and control groups were recorded in details.35 days after subcutaneous transplantation, all the nude mice were anatomized and subcutaneous tumors were observed by H.E staining.
3.The protein expression differences of Cholangiocarcinoma QBC939 cell subcutaneous tumors were detected by proteomics.
4.To explore the mRNA and protein levels of Bcl-2 and Bax in Cholangiocarcinoma QBC939 cell subcutaneous tumors and its possible mechanism. the samples of the experimental and control groups were detected by RT-PCR and Western blot.
Results:
1. The growth of cholangiocarcinoma cells QBC939 could be inhibited by Centipede Aqueous Extract. With gradually increasing concentration its anti-tumor effect was also enhanced too. Its IC50 value of 48 hours was 12.5mg/ml. and Centipede Aqueous Extract could also inhibit the colony-forming of cholangiocarcinoma cell line QBC939 cells. Electron microscopy showed that the apoptosis bodies could be seen clearly in Centipede Aqueous Extract treatment cholangiocarcinoma QBC939 cells by the concentration of 12.5mg/ml after 48h.
2. Successfully established were the nude mice subcutaneous tumors model of Cholangiocarcinoma QBC939 cells. After fed with of Centipede Aqueous Extract on the concentration of 10g/kg, Obvious different Growth rates were observed between the treatment group and control groups; Plenty of vacuolization and karyopyknosis cells were seen in experimental group by HE staining,rarely in the control group.
3. Compared to 38 proteins differentially expressed significantly in Cholangiocarcinoma QBC939 subcutaneous tumors tissues, among which 27 ribosomal protein genes were down-regulated significantly, while 11 ribosomal protein genes were up-regulated. CK8、CK18及Bcl-2 were down-regulated while Galectin-1 and Galectin-7 genes were down-regulated.
4. The result of RT-PCR and Western blot showed that the mRNA and protein levels of Bax were increased and those of Bcl-2 were declined in the experimental groups compared to the control groups
Conclusion:
1. Cholangiocarcinoma QBC939 cells could be inhibited by Centipede Aqueous Extract in vitro. With gradually increasing concentration its anti-tumor effect was also enhanced too. Its IC50 value was 12.5mg/ml.
2. Successfully established were the nude mice subcutaneous tumors model of Cholangiocarcinoma QBC939 cells. Centipede Aqueous Extract with the concentration of lOg/kg might have anti-tumor effect on the nude mice subcutaneous tumors.
3. There were 38 proteins differentially expressed significantly in Cholangiocarcinoma QBC939 cells subcutaneous tumors tissues, CK8、CK18 and Bcl-2 were down-regulated while Galectin-1 and Galectin-7 genes were down-regulated.
4. The apoptosis mechanism of treatment group Cholangiocarcinoma cells might be that up-regulated Bax and down-regulated Bcl-2 by Centipede Aqueous Extract.
引文
1.田雨霖.肝门部胆管癌国内外科治疗40年回顾.中国实用外科杂志2007(5)；347-350.
2.Thomas H, Heaton ND. Late recurrence after surgery for cholangiocarcinoma: implications for follow-up? Hepatobiliary Pancreat Dis Int 2008;7:544-546
3.Ito Y, Tajima Y, Fujita F, et al. Solitary recurrence of hilar cholangiocarcinoma in a mediastinal lymph node two years after curative resection. World J Gastroenterol 2007; 13:2243-2246
4.Weber SM, Jarnagin WR, Klimstra D, et al. Intrahepatic cholangiocarcinoma: resectability, recurrence pattern, and outcomes. J Am Coll Surg 2001;193:384-391
5.Lang M, Henson R, Braconi C, Patel T. Epigallocatechin-gallate modulates chemotherapy-induced apoptosis in human cholangiocarcinoma cells. Liver Int 2009
6.Thongprasert S. The role of chemotherapy in cholangiocarcinoma. Ann Oncol 2005;16 Suppl2:ii93-96
7.陈华江,钟延强,贾连顺等.三氧化二砷白蛋白微球的理化特性及抗肿瘤活性检测.第二军医大学学报2007(5),644-646.
8.桑玉旗.三氧化二砷治疗多发性骨髓瘤的疗效及其作用机制.山东医药2007(25),40-41.
9.刘晓川,刘铁夫.缺氧时三氧化二砷对人肝癌细胞株bel-7402生长及凋亡的影响及机制.世界华人消化杂志2007(18),1983-1988.
10.黄建,陈康杰,张卧等.苦参碱抑制人大肠癌ht29细胞增殖及诱导凋亡作用与机制.中草药2007(8),1210-1214.
11.胡建莉,伍钢,肖兰.氧化苦参碱对人食管癌细胞株Eca109增殖及凋亡的影响.中国医院药学杂志2007(12),1662-1665.
12.Pushkarev VM, Starenki DV, Saenko VA, et al. Effects of low and high concentrations of antitumour drug taxol in anaplastic thyroid cancer cells. Exp Oncol 2009;31:16-21
13.Kumaran RS, Muthumary J, Hur BK. Isolation and identification of an anticancer drug, taxol from Phyllosticta tabernaemontanae, a leaf spot fungus of an angiosperm, Wrightia tinctoria. J Microbiol 2009;47:40-49
14.吕必华,张玲,朱长才等.姜黄素抑制HepG2细胞HDAC1活性及促进P21-(WAF1/CIP1)表达的研究.中国中药杂志2007(12),2051-2055.
15.邓刚,余建华,叶章群.姜黄素对雄激素非依赖性前列腺癌细胞Notch 1表达和分布的影响华中科技大学学报2007(6),740-743.
16.周永芹,韩莉.中药蜈蚣的研究进展.中药材2008(2),315-319.
17.赵志国,李军云,蒋晔等.蜈蚣酸性蛋白对急性心力衰竭大鼠心功能的影响.北京中医药大学学报2008(2),106-109.
18.曾红.蜈蚣中抗癌活性成分的提取.湖南中医杂志2004(5),57-58.
19.韩莉,周永芹,韩钰.·蜈蚣提取物诱导宫颈癌HeLa细胞凋亡及其机制的研究.时珍国医国药2007(9),2109-2111.
20.刘峰.蜈蚣的临床应用及其毒性研究.广西中医药1999(4),54-55.
21.任文华张宋周.少棘蜈蚣毒腺RACE cDNA文库的构建及β-actin基因的克隆与序列分析.动物学杂志2005(5),54-55
22.任文华,张双全,宋大祥等.少棘蜈蚣毒液溶血肽的分离纯化.动物学报2007(3),519-523
23.焦波,娄红祥,王东兴.蜈蚣提取液对小鼠精原细胞的作用.山东医科大学学报1999(4),358-362
24.司秋菊,王鑫国,白霞.蜈蚣对动脉粥样硬化家兔血液流变学的影响.中国老年学杂志2004；24(9)：831-833
25.杨培.中药：在美国的地位和fda政策.中国药科大学学报2007(5),385-390
26.唐健元,张磊,杜晓曦.国外上市植物药评价简介和对我国中药新药临床研究现状的思考.中药药理与临床2007(5),222-227
27.侯桂兰,芦柏震,王春雷.化疗药物所致消化系统毒副反应的中药防治.中华中医药学刊2008(8),1799-1801
28.张晓宇,吴雄志.中药减轻化疗毒性反应研究进展.辽宁中医药大学学报2007(6),187-189
29.许尤琪,丁蓉,张玉等.中药配合化疗治疗晚期非小细胞肺癌疗效观察.辽宁中医杂志2007(7),916-917
30.李蕾.中药多糖对环磷酰胺的增效减毒作用.中国热带医学2008(4),685-687
31.李凤云 陈张刘.中药制剂抗肿瘤作用的实验研究.中医药学报1999(5),57
32.李厚伟,张妍,许超千等.中药HB对喉癌Hep-2细胞的抑制作用及其机制研究.哈尔滨医科大学学报2001(4),55-56
33.刘国清,田秉漳,皮执民等.蜈蚣油性提取液对肝癌细胞增殖的影响.中国现代医学杂志2002(4),22-23
34.曲爱兵,赵维诚,梁良等.蜈蚣组织提取物抗肿瘤活性的初步研究.实用肿瘤学杂志2003(1),29-30
35.Yoshizaki T, Endo K, Ren Q, et al. Oncogenic role of Epstein-Barr virus-encoded small RNAs (EBERs) in nasopharyngeal carcinoma. Auris Nasus Larynx 2007;34:73-78
36.Li H, Ou X, Xiong J. Modified HPV16 E7/HSP70 DNA vaccine with high safety and enhanced cellular immunity represses murine lung metastatic tumors with downregulated expression of MHC class I molecules. Gynecol Oncol 2007;104:564-571
37.Kaneko T, Zhang Z, Mantellini MG, et al. Bcl-2 orchestrates a cross-talk between endothelial and tumor cells that promotes tumor growth. Cancer Res 2007;67:9685-9693
38.Lovas JG. Apoptosis in human epidermis:a postmortem study by light and electron microscopy. Australas J Dermatol 1986;27:1-5
39.Frey TG, Sun MG. Correlated light and electron microscopy illuminates the role of mitochondrial inner membrane remodeling during apoptosis. Biochim Biophys Acta 2008;1777:847-852
40.Kerr JF, Wyllie AH, Currie AR. Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972;26:239-257
41.Evangelou K, Bramis J, Peros I, et al. Electron microscopy evidence that cytoplasmic localization of the pl6(INK4A) "nuclear" cyclin-dependent kinase inhibitor (CKI) in tumor cells is specific and not an artifact. A study in non-small cell lung carcinomas. Biotech Histochem 2004;79:5-10
42.刘细平.蜈蚣提取液治疗肝细胞肝癌的实验研究.中国博士学位论文数据库(2007)。
43.王曙光,韩本立,段恒春,陈意生,彭志明.肝外胆管癌细胞系的建立.中华实验外科杂志1997(2),67-68
44.王曙光 陈李李.胆管癌细胞层粘连蛋白受体表达下调对蛋白水解酶尿激酶型纤维蛋白溶解酶原激酶mRNA表达的影响.中华医学杂志2004(19),62-64
45.Pernet P, Bruneel A, Baudin B, Vaubourdolle M. PHProteomicDB:a module for two-dimensional gel electrophoresis database creation on personal web sites. Genomics Proteomics Bioinformatics 2006;4:134-136
46.Pyndiah S, Lasserre JP, Menard A, et al. Two-dimensional blue native/SDS gel electrophoresis of multiprotein complexes from Helicobacter pylori. Mol Cell Proteomics 2007;6:193-206
47.Carrette O, Burkhard PR, Sanchez JC, Hochstrasser DF. State-of-the-art two-dimensional gel electrophoresis:a key tool of proteomics research. Nat Protoc 2006;1:812-823
48. Oh-Ishi M, Maeda T. Disease proteomics of high-molecular-mass proteins by two-dimensional gel electrophoresis with agarose gels in the first dimension (Agarose 2-DE). J Chromatogr B Analyt Technol Biomed Life Sci 2007;849:211-222
49.Zheng YZ, Foster LJ. Biochemical and proteomic approaches for the study of membrane microdomains. J Proteomics 2009;72:12-22
50.Wang X, Chen Y, Han QB, et al. Proteomic identification of molecular targets of gambogic acid:role of stathmin in hepatocellular carcinoma. Proteomics 2009;9:242-253
51.Sonck KA, Kint G, Schoofs G, et al. The proteome of Salmonella Typhimurium grown under in vivo-mimicking conditions. Proteomics 2009;9:565-579
52.Seeber B, Sammel MD, Fan X, et al. Proteomic analysis of serum yields six candidate proteins that are differentially regulated in a subset of women with endometriosis. Fertil Steril 2009
53.Wingren C, James P, Borrebaeck CA. Strategy for surveying the proteome using affinity proteomics and mass spectrometry. Proteomics 2009
54.Tian R, Wei LM, Qin RY, et al. Proteome analysis of human pancreatic ductal adenocarcinoma tissue using two-dimensional gel electrophoresis and tandem mass spectrometry for identification of disease-related proteins. Dig Dis Sci 2008;53:65-72
55.Remmerie N, Roef L, Van De Slijke E, et al. A bioanalytical method for the proteome wide display and analysis of protein complexes from whole plant cell lysates. Proteomics 2009;9:598-609
56.Doud MK, Schmidt MW, Hines D, et al. Rapid prefractionation of complex protein lysates with centrifugal membrane adsorber units improves the resolving power of 2D-PAGE-based proteome analysis. BMC Genomics 2004;5:25
57. Wu WW, Wang G, Baek SJ, Shen RF. Comparative study of three proteomic quantitative methods, DIGE, cICAT, and iTRAQ, using 2D gel-or LC-MALDI TOF/TOF. J Proteome Res 2006;5:651-658
58.Zhou J, Liang S, Fang L, et al. Quantitative Proteomic Analysis of HepG2 Cells Treated with Quercetin Suggests IQGAP1 Involved in Quercetin-Induced Regulation of Cell Proliferation and Migration. OMICS 2009
59.Schiess R, Mueller LN, Schmidt A, et al. Analysis of cell surface proteome changes via label-free, quantitative mass spectrometry. Mol Cell Proteomics 2008
60.Ishida Y, Yamashita K, Sasaki H, et al. Activation of complement system in adult T-cell leukemia (ATL) occurs mainly through lectin pathway:a serum proteomic approach using mass spectrometry. Cancer Lett 2008;271:167-177
61.Ahmad Y, Boisvert FM, Gregor P, Cobley A, Lamond AI. NOPdb:Nucleolar Proteome Database-2008 update. Nucleic Acids Res 2009;37:D181-184
62.Leung AK, Trinkle-Mulcahy L, Lam YW, et al. NOPdb:Nucleolar Proteome Database. Nucleic Acids Res 2006;34:D218-220
63.Fleissig Y, Deutsch O, Reichenberg E, et al. Different proteomic protein patterns in saliva of Sjogren's syndrome patients. Oral Dis 2009;15:61-68
64.Zhang L, Wang X, Peng X, et al. Immunoaffinity purification of plasma membrane with secondary antibody superparamagnetic beads for proteomic analysis. J Proteome Res 2007;6:34-43
65.Wright JC, Hubbard SJ. Recent developments in proteome informatics for mass spectrometry analysis. Comb Chem High Throughput Screen 2009; 12:194-202
66. Dani N, Stilla A, Marchegiani A, et al. Combining affinity purification by ADP-ribose-binding macro domains with mass spectrometry to define the mammalian ADP-ribosyl proteome. Proc Natl Acad Sci U S A 2009
67.Krauss S, Franke WW. Organization and sequence of the human gene encoding cytokeratin 8. Gene 1990;86:241-249
68.Chen N, Gong J, Chen X, et al. Cytokeratin expression in malignant melanoma:potential application of in-situ hybridization analysis of mRNA. Melanoma Res 2009;19:87-93
69.Ausch C, Buxhofer-Ausch V, Olszewski U, et al. Caspase-cleaved cytokeratin 18 fragment (M30) as marker of postoperative residual tumor load in colon cancer patients. Eur J Surg Oncol 2009
70.Xu W, Zhang MW, Huang J, et al. Correlation between CK18 gene and gastric carcinoma micrometastasis. World J Gastroenterol 2005;11:6530-6534
71.Yilmaz Y, Dolar E, Ulukaya E, et al. Elevated serum levels of caspase-cleaved cytokeratin 18 (CK18-Asp396) in patients with nonalcoholic steatohepatitis and chronic hepatitis C. Med Sci Monit 2009;15:CR189-193
72.Saussez S, Cludts S, Capouillez A, et al. Identification of matrix metalloproteinase-9 as an independent prognostic marker in laryngeal and hypopharyngeal cancer with opposite correlations to adhesion/growth-regulatory galectins-1 and-7. Int J Oncol 2009;34:433-439
73.Harjacek M, Diaz-Cano S, De Miguel M, et al. Expression of galectins-1 and-3 correlates with defective mononuclear cell apoptosis in patients with juvenile idiopathic arthritis. J Rheumatol 2001;28:1914-1922
74.Rabinovich GA, Gruppi A. Galectins as immunoregulators during infectious processes:from microbial invasion to the resolution of the disease. Parasite Immunol 2005;27:103-114
75.Salatino M, Croci DO, Bianco GA, et al. Galectin-1 as a potential therapeutic target in autoimmune disorders and cancer. Expert Opin Biol Ther 2008;8:45-57
76.Camby I, Le Mercier M, Lefranc F, Kiss R. Galectin-1:a small protein with major functions. Glycobiology 2006;16:137R-157R
77.Saussez S, Kiss R. Galectin-7. Cell Mol Life Sci 2006;63:686-697
78.Xiao D, Zhang L. Upregulation of Bax and Bcl-2 following prenatal cocaine exposure induces apoptosis in fetal rat brain. Int J Med Sci 2008;5:295-302
79. Zhang YJ, Dai Q, Wu SM, et al. Susceptibility for NSAIDs-induced apoptosis correlates to p53 gene status in gastric cancer cells. Cancer Invest 2008;26:868-877
80.Young KH, Xie Q, Zhou G, et al. Transformation of follicular lymphoma to precursor B-cell lymphoblastic lymphoma with c-myc gene rearrangement as a critical event. Am J Clin Pathol 2008;129:157-166
81.Demidchik V, Shang Z, Shin R, et al. Plant extracellular ATP signalling by plasma membrane NADPH oxidase and Ca(2+) channels. Plant J 2009
82.del Riego G, Casano LM, Martin M, Sabater B. Multiple phosphorylation sites in the beta subunit of thylakoid ATP synthase. Photosynth Res 2006;89:11-18
83.Cipriano DJ, Dunn SD. The role of the epsilon subunit in the Escherichia coli ATP synthase. The C-terminal domain is required for efficient energy coupling. J Biol Chem 2006;281:501-507
84.Eastman A, Rigas JR. Modulation of apoptosis signaling pathways and cell cycle regulation. Semin Oncol 1999;26:7-16; discussion 41-12
85.Tsujimoto Y, Cossman J, Jaffe E, Croce CM. Involvement of the bcl-2 gene in human follicular lymphoma. Science 1985;228:1440-1443
86.Suzuki A, Umezawa A, Sano M, Nozawa S, Hata J. Involvement of EAT/mcl-1, a bcl-2 related gene, in the apoptotic mechanisms underlying human placental development and maintenance. Placenta 2000;21:177-183
87.Sano M, Umezawa A, Suzuki A, et al. Involvement of EAT/mcl-1, an anti-apoptotic bcl-2-related gene, in murine embryogenesis and human development. Exp Cell Res 2000;259:127-139
88.Bakhshi A, Jensen JP, Goldman P, et al. Cloning the chromosomal breakpoint of t(14;18) human lymphomas:clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell 1985;41:899-906
89. O'Neill J, Manion M, Schwartz P, Hockenbery DM. Promises and challenges of targeting Bcl-2 anti-apoptotic proteins for cancer therapy. Biochim Biophys Acta 2004; 1705:43-51
90. Guo LL, Xiao S, Guo Y. Detection of bcl-2 and bax expression and bcl-2/JH fusion gene in intrahepatic cholangiocarcinoma. World J Gastroenterol 2004;10:3251-3254
91. Rao RV, Hermel E, Castro-Obregon S, et al. Coupling endoplasmic reticulum stress to the cell death program. Mechanism of caspase activation. J Biol Chem 2001;276:33869-33874
92.郭铁军,周振华,黄灼宏等.连休蜈蚣地龙汤对支原体肺炎患儿免疫功能的影响.新中医2007(1),19-21
93.曹勇,钟安朴,夏清华等.化瘀破癥胶囊干预荷瘤小鼠血清肿瘤坏死因子活性的变化.中国临床康复2006(23),118-120
94.Reynolds JL, Mahajan SD, Sykes D, Nair MP. Heroin-Induces Differential Protein Expression by Normal Human Astrocytes (NHA). Am J Infect Dis 2006;2:49-57
95. Wang WL, Yeh SF, Huang EY, et al. Mitochondrial anchoring of PKCalpha by PICK1 confers resistance to etoposide-induced apoptosis. Apoptosis 2007;12:1857-1871
96. Samaras V, Tsopanomichalou M, Stamatelli A, et al. Is there any potential link among caspase-8, p-p38 MAPK and bcl-2 in clear cell renal cell carcinomas? A comparative immunohistochemical analysis with clinical connotations. Diagn Pathol 2009;4:7
97. Wang M, Tsai BM, Reiger KM, Brown JW, Meldrum DR.17-beta-Estradiol decreases p38 MAPK-mediated myocardial inflammation and dysfunction following acute ischemia. J Mol Cell Cardiol 2006;40:205-212
98. Kuwabara I, Kuwabara Y, Yang RY, et al. Galectin-7 (PIG1) exhibits pro-apoptotic function through JNK activation and mitochondrial cytochrome c release. J Biol Chem 2002;277:3487-3497
99. Wei Y, Pattingre S, Sinha S, Bassik M, Levine B. JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell 2008;30:678-688
100.Yuan ZQ, Feldman RI, Sussman GE, et al. AKT2 inhibition of cisplatin-induced JNK/p38 and Bax activation by phosphorylation of ASK1: implication of AKT2 in chemoresistance. J Biol Chem 2003;278:23432-23440
101.Schafer B, Quispe J, Choudhary V, et al. Mitochondrial Outer Membrane Proteins Assist Bid in Bax-mediated Lipidic Pore Formation. Mol Biol Cell 2009
102.Youdim MB, Arraf Z. Prevention of MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) dopaminergic neurotoxicity in mice by chronic lithium: involvements of Bcl-2 and Bax. Neuropharmacology 2004;46:1130-1140
103.Eldering E, Mackus WJ, Derks IA, et al. Apoptosis via the B cell antigen receptor requires Bax translocation and involves mitochondrial depolarization, cytochrome C release, and caspase-9 activation. Eur J Immunol 2004;34:1950-1960
104.Isonishi S, Saitou M, Yasuda M, Tanaka T. Mitochondria in platinum resistant cells. Hum Cell 2001;14:203-210
105.Matsuyama S, Llopis J, Deveraux QL, Tsien RY, Reed JC. Changes in intramitochondrial and cytosolic pH:early events that modulate caspase activation during apoptosis. Nat Cell Biol 2000;2:318-325
106.Zhang B, Luo Y, Weng Q, et al. CPT21, a novel compound with anti-proliferative effect against gastric cancer cell SGC7901. Invest New Drugs 2008;26:517-524
107.Yang S, Hu S, Chen J, et al. Mechanism of hepatoprotection in proestrus female rats following trauma-hemorrhage:heme oxygenase-1-derived normalization of hepatic inflammatory responses. J Leukoc Biol 2009
108.Wu JN, Huang J, Yang J, et al. Caspase inhibition augmented oridonin-induced cell death in murine fibrosarcoma 1929 by enhancing reactive oxygen species generation. J Pharmacol Sci 2008; 108:32-39
109.Ferreira R, Neuparth MJ, Vitorino R, et al. Evidences of apoptosis during the early phases of soleus muscle atrophy in hindlimb suspended mice. Physiol Res 2008;57:601-611
110.Zurgil N, Afrimzon E, Shafran Y, et al. Lymphocyte resistance to lysophosphatidylcholine mediated apoptosis in atherosclerosis. Atherosclerosis 2007; 190:73-83
111.Zhang QY, Jiang M, Zhao CQ, et al. Apoptosis induced by one new podophyllotoxin glucoside in human carcinoma cells. Toxicology 2005;212:46-53
112.Zhang G, Matsumoto S, Hyon SH, et al. Polyphenol, an extract of green tea, increases culture recovery rates of isolated islets from nonhuman primate pancreata and marginal grade human pancreata. Cell Transplant 2004; 13:145-152
[1]Patel T, Singh P.Cholangiocarcinoma:emerging approaches to a challenging cancer[J].Curr Opin Gastroenterol,2007,23(3):317-323.
[2]Jasmine LH,Thomas RB,Faye TL,etal.Outcomes after resection of cholangio-cellular carcinoma[J]. Am J Surg,2004,187 (5):612-617.
[3]Dnes MJ,Erlich R, Matthew JO,Rodrigo E.A review and update on cholangiocarcinoma[J].Oncol,2004,66(3):167-179.
[4]Berthiaume EP,Wands J.The molecular pathogenesis of cholangiocarcinoma [J]. Semin Liver Dis,2004,24(2):127-137.
[5]Ito Y, Takeda T, Sasaki Y, et al.Bcl-2 expression in cholangiocellular carcinoma is inversely correlated with biologically aggressive phenotypes[J]. Oncology,2000,59(1):63-67.
[6]Li SM, Yao SK, Yamamura N, et al.Expression of Bcl-2 and Bax in extrahepatic biliary tract carcinoma and dysplasia [J].World Jgastroenterol,2003,9(11): 2579-2582.
[7]Su WC, Shiesh SC, Liu HS, et al.Expression of oncogene productsHER2 /Neu and Ras and fibrosis-related growth factors bFGF, TGF-beta, and PDGF in bile from biliarymalignancies-and inflammatory disorders[J].Dig Dis Sci,2001,46(7): 1387-1392.
[8]Ukita Y, KatoM, Terada T. Gene amplification and mRNA and protein over-expression of c-erbB-2 (HER-2/neu) in human intrahepatic cholangiocarcinoma as detected by fluorescence in situ hybridization, in situ hybridization, and immunohistochemistry[J]. J Hepato,l 2002,36(6):780-785.
[9]Aishima SI, Taguchi KI, Sugimachi K, et al.c-erbB-2 and c-Met expression relates to cholangiocarcinogenesis and progression of intrahepatic cholan-giocarcinoma [J].Histopathology,2002,40(3):269-278.
[10]BobergKM, SchrumpfE, BergquistA, eta.l Cholangiocarcinomain primary sclerosing cholangitis:K-rasmutations and Tp53 dysfunction are implicated in the neoplastic development[J]. Hepatol,2000,32(3):374-380.
[11]Isa T,Tomita S,NakachiA,et al.Analysis of microsatellite instability, K-ras genemutation and p53 protein overexpression in intrahepatic cholangio-carcinoma[J]. Hepatogastroenterology,2002,49(45):604-608.
[12]Voravud N,Foster CS,Gilbertson JA,et al,Oncogene expressionin cholangio-carcinoma and in normal hepatic development[J].Hum Pathol,1989,20(12): 1163-1168.
[13]Limpaiboon T, Sripa B,Wongkham S, et al.Anti-p53 antibodiesand p53 protein expression in cholangiocarcinoma[J]. Hepatogastroenterology,2004,51 (55):25-28.
[14]Wang Y, Yamaguchi Y, Watanabe H, et al,Usefulness of p53 gene mutations in the supernatant of bile for diagnosis of biliary tract carcinoma: comparison with K-rasmutation[J]. Gastroenterol,2002,37 (10):831-839.
[15]Argani P, Shaukat A,Kaushal M, et al.Differing rates of loss of DPC4 expression and of p53 overexpression among carcinomas of the proximal and distal bile ducts[J].Cancer,2001,91(7):1332-1341.
[16]Tang Z, Zou S, Hao Y, et al,Frequency of loss expression of the DPC4 protein in various locations of biliary tract carcinoma[J]. ZhonghuaYu FangYiXue Za Zhi,2002,36(7):481-484.
[17]Fujii K,Yasui W,Shimamoto F,et al.Immunohistochemical analysis of nm23 gene product in human gallbladder carcinomas[J]. VirchowsArch,1995,426(4): 355-359.
[18]Benckert C,Jonas S,Cramer T,et al.Transforming growth factor beta 1 stimulates vascular endothelial growth factor gene transcription in human cholangiocellular carcinoma cells[J]. CancerRes,2003,63(5):1083-1092.
[19]Kawahara N,Ono M,Taguchi K,et al.Enhanced expression of thrombospondin-1 and hypovascularity in human cholangiocarcinoma[J]. Hepatology, 1998,28(6):1512-1517.
[20]Ogasawara S,Yano H,HigakiK,et al.Expression of angiogeni factors, basic fibroblast growth factor and vascular endothelia growth factor, in human biliary tract carcinoma cell lines[J]. Hepatol Res,2001,20(1):97-113.
[21]Xiao M,Zhou N X,Huang ZQ,et al.The ratio of MMP-2 tTIMP-2 in hilar cholangiocarcinoma:a semi-quantitative study [J].Hepatobiliary Pancreat Dis Int, 2004,3(4):599-602.
[22]Miwa S,Miyagawa S,Soeda J,et al.Matrixmetalloproteinase expression and biologic aggressiveness of cholangiocellular carcinoma [J].Cancer,2002,94(2): 428-434.
[23]Zheng XH,Wang XG,Yan XC,et al.Expression and significance of integrin avβ3 in human bile ductcarcinoma[J].Acta Academae Medicinae Militaris Tertiae,2005,27(12):1276-1278.
[24]Tsuchikawa T,Kondo S,Hirano S,et al.Long-term survival after curative left hepatectomy formucin-producing cholangiocarcinoma:report of a case[J].Surg Today,2005,35(3):256-258.
[25]Higashi M,Yonezawa S,Ho JJ,et al.Expression of MUC1 and MUC2 mucin antigens in intrahepatic bile duct tumors:its relationship with a new morphological classification of cholangiocarcinom[J]. Hepatology,1999,30(6):1347-1355.
[26]Bjornsson E,Kilander A,Olsson R.CA19-9 and CEA are unrelable markers for cholangiocarcinoma in patients with primary sclerosing cholangitis[J].Liver,1999, 19(6):501-508.
[27]Okami J,Dohno K,Sakon M,et al.Genetic detection for micrometastasis in lymph node of biliary tract carcinoma[J].Clin Cance Res,2000,6(6):2326-2332.
[28]Patel AH,Harnois DM,Klee GG,et al.The utility of CA19-9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis[J].Am J Gastroenterol,2000,95 (1):204-207.
[29]Ramage JK,Donaghy A,Farrant JM,et al.Serum tumor markers for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis[J]. Gastroente-rology,1995,108(3):865-869.
[30]Watanabe M,Chigusa M,Takahashi H,et al.High level of Cal9-9,CA50,and CEA-producible human cholangiocarcinoma cell line changes in the secretion ratios in vitro or in vivo[J].In Vitro Cell Dev Biol Anim,2000,36(2):104-109.
[31]Pasanen PA,Eskelinen M,Partanen K,et al.Clinical value of serum tumour markers CEA, CA 50 and CA242 in the distinction between malignant versus benign diseases causing jaundice and cholestasis;results from a prospective study[J]. Anticancer Res,1992,12(5):1687-1693.
[32]Enjoji M,Yamaguchi K,Nakamuta M,etal.Movement of a novel serum tumour marker, RCAS1, in patients with biliary diseases[J].Dig Liver Dis,2004,36(9): 622-627.
[33]Watanabe H,Enjoji M,Nakashima M,et al.Clinical significance of serum RCAS1 levels detected by monoclonal antibody 22-1-1 in patients with cholangiocellular carcinoma[J].Hepatol,2003,39(4):559-563.
[34]Suzuoki M,Hida Y,Miyamoto M,et al.RCAS1 expression as aprognostic factor after curative surgery for extrahepatic bile duct carcinoma[J].Ann Surg Oncol,2002,9(4):388-393.
[35]Kanno N,Glaser S,Chowdhury U,et al.Gastrin inhibits cholangiocarcinoma growth through increased apoptosis by activation of Ca2+-dependent protein kinase C-alpha[J].Hepatol,2001,34(2):284-291.
[36]Caplin M,Khan K,Savage K,et al.Expression and processing of gastrin in hepatocellular carcinoma, fibrolamellar carcinoma and cholangiocarcinoma[J]. Hepatol,1999,30(3):519-526.
[37]Zhao B,Zhao H,Zhao N,et al.Cholangiocarcinoma cells express somatostatin receptor subtype 2 and respond to octreotide treatment[J].Hepatobiliary Pancreat Surg,2002 9(4):497-502.
[38]Lie-A-Ling M,Bakker CT,Deurholt T,et al.Selection of tumour specific promoters for adenoviral gene therapy of cholangiocarcinoma[J].Hepatol,2006, 44(1):126-133.
[39]Itoi T,Shinohara Y,Takeda K,et al.Detection of telomerase reverse transcriptase mRNA in biopsy specimens and bile for diagnosis of biliary tract cancers[J].Int J Mol Med,2001,7(3):281-287.
[40]Washburn WK,Lewis WD,Jenkins RL.Aggressive surgical resection for cholangiocarcinoma[J]. Arch Surg,1995,130(3):270-276.
[41]Tangkijvanich P,Thong-ngam D,Theam-boonlers A, et al.Diagnostic role of serum interleukin 6 and CA19-9 in patients with cholangiocarcinoma[J]. Hepatogastroenterology,2004,51 (55):15-19.
[42]Chen CY,Lin XZ,WuHC,et al.The value of biliary amylase and Hepatocarcinoma-Intestine-Pancreas/Pancreatitis-associated Protein I (HIP/PAP-I) in diagnosing biliary malignancies [J]. Clin Biochem,2005,38(6):520-525.
[43]Kipp BR,Stadheim LM,HallingSA,et al.Acomparison of routine cytology and fluorescence in situ hybridization for the detection bile duct strictures[J].Am J Gastroenterol,2004,99(9):1675-1681.
[44]Poneros JM,Tearney GJ,Shiskov M,et al.Optical coherence tomography of the biliary tree during ERCP[J].Gastrointest Endosc,2002,55(1):84-88.
[45]Xu HX, Lu MD, Liu GJ,et al.Imaging of peripheral cholangiocarcinoma with low-mechanical index contrast-enhanced sonography and SonoVue:initial experience [J]. Ultrasound Med,2006,25(1):23-33.
[46]Sakata J, Shirai Y,Wakai T, et al.Catheter tract implantation metastases associated with percutaneous biliary drainage for extrahepatic cholangiocarcinoma[J]. World J Gastroenterol,2005,11(44):7024-7027.
[47]Christensen M,Matzen P, Schulze S, et al.Complications of ERCP:a prospective study[J].Gastrointest Endosc,2004,60 (5):721-731.
[48]Kim HJ, Kim AY, Hong SS, et al.Biliary ductal evaluation of hilar cholangiocarcinoma:three-dimensional direct multi-detector row CT cholangiographic findings versus surgical and pathologic results feasibility study[J].Radiology,2006, 238(1):300-308.
[49]Stroszczynski C,Hunerbein M.Malignant biliary obstruction:value of imaging findings[J]. Abdom Imaging,2005,30 (3):314-323.
[50]Olnes MJ,Erlich R.A review and update on cholangiocarcinoma[J]. Oncology,2004,66(3):167-179.
[51]Khan SA,Thomas HC,Davidson BR,et al.Cholangiocarcinoma [J].Lancet,2005,366(9493):1303-1314.
[52]Reddy SB,Patel T.Current approaches to the diagnosis and treatment of cholangiocarcinoma [J].Curr Gastroenterol Rep,2006,8(1):30-37.
[53]Nakeeb A, Tran KQ, Black MJ,et al.Improved survival in resected biliary malignancies [J].Surgery,2002,132(4):555-563.
[54]杨维良,张东伟,佟佰峰,等。肝门部胆管癌165例的诊断与外科治疗。中华肝胆外科杂志。2006,12(8)：512-514。
[55]黎介寿,吴孟超,黄志强.普通外科手术学[M].北京：人民军医出版社,2005：728-732.
[56]Kawasaki S,Imamura H,Kobayashi A,et al.Results of surgical resection for patients with hilar bile duct cancer:application of extended hepatectomy after biliary drainage and hemihepatic portal vein embolization[J].Ann Surg,2003,238(1):84-92.
[57]Ortner ME,Caca K,BerrF,et al.Successful photodynamic therapy for non resectable cholangiocarcinoma:a randomized prospective study[J].Gastroentero-logy,2003,125(5):1355-1363.
[58]Varotti G,Gondolesi GE,Roayaie S,et al.Combined adult-to-adult living donor right lobe liver transplantation and pancreatoduodenectomy for distal bile duct adenocarcinoma in a patient with primary sclerosing cholangitis[J].J Am Coll Surg,2003,197(5):765-769.
[59]詹文华,何晓顺,朱晓峰,等.亚洲首例胰腺癌并肝脏多发转移患者上腹部器官簇移植成功[J].中华胃肠外科杂志,2004,7(4)：335.
[60]Seyama Y,Makuuchi M.Current surgical treatment for bile duct cancer.World J Gastroenterol,2007,13(10):1505-1515.
[61]McMasters KM,Tuttle TM,Leach SD,et al.Neoadjuvant chemoradiation for extrahepatic cholangiocarcinoma[J]. Am J Surg,1997,174(6):605-608.
[62]Wiedmann M,Caca K,Berr F,et al.Neoadjuvant photodynamic therapy as a new approach to treating hilar cholangiocarcinoma:aphase II pilot study[J].Cancer, 2003,97(11):2783-2790.
[63]Khan SA,Davidson BR,GoldinR, etal.Guidelines for the diagnosis and treatment of cholangiocarcinoma:consensus document[J].Gut,2002,51 (Suppl6): VI1-9.
[64]Mittal B,Deutsch M,Iwatsuki S.Primary cancers of extrahepatic biliary passages[J]. Int J Radiat Oncol Biol Phys,1985,11(4):849-854.
[65]Glimelius B,Hoffman K,Sjoden PO,et al.Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cance[J].Ann Oncol,1996,7(6): 593-600.
[66]Thongprasert S.The role of chemotherapy in cholangiocarcinoma[J]. Ann Oncol,2005,16 (Suppl2):ii93-96.
[67]Choi CW,Choi IK,Seo JH,et al.Effects of 5-fluorouracil and leucovorin in the treatment of pancreatic-biliary tract adenocarcinomas[J]. Am J Clin Oncol,2000, 23(4):425-428.
[68]Ducreux M,Rougier P,Fandi A,et al.Effective treatment of advanced biliary tract carcinoma using 5-fluorouracil continuous infusion with cisplatin[J].Ann Oncol, 1998,9(6):653-656.
[69]Lee MA,Woo IS,Kang JH,et al.Epirubicin,cisplatin,and protracted infusion of 5-FU (ECF) in advanced intrahepatic cholangiocarcinoma [J].Cancer Res Clin Oncol,2004,130 (6):346-350.
[70]Patt YZ,Hassan MM,Aguayo A,et al.Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma, and gall bladder carcinoma[J]. Cancer,2004,101(3):578-586.
[71]Dingle BH,Rumble RB,BrouwersMC,et al.The role of gemcitabine in the treatment of cholangiocarcinoma and gallbladder cancer:a systematic review[J]. Can J Gastroenterol,2005,19(12):711-716.
[72]Andre T,Tournigand C,Rosmorduc O,et al.Gemcitabine combined with oxaliplatin (GEMOX) in advanced biliary tractadenocarcinoma:a GERCOR study[J].Ann Oncol,2004,15(9):1339-1343.
[73]Alberts SR,Fishkin PA,Burgart LJ,et al.CPT-11 for bile-duct and gallbladder carcinoma:a phase Ⅱ North Central Cancer Treatment Group (NCCTG) study[J]. Int J Gastrointest Cancer,2002,32(2-3):107-114.
[74]JonesDV,LozanoR,HoqueA,et al.Phase Ⅱ study of paclitaxe therapy for unresectable biliary tree carcinomas[J]. Clin Oncol,1996,14(8):2306-2310.
[75]Papakostas P,Kouroussis C,Androulakis N,et al.First-line chemotherapy with docetaxel for unresectable or metastatic carcinoma of the biliary tract. A multicentre phase Ⅱ study[J].Eur J Cancer,2001,37(15):1833-1838.
[76]Pitt HA,Nakeeb A,Abrams RA,et al.Perihilar cholangiocarcinoma. Postoperative radiotherapy does not improve survival[J]. AnnSurg,1995,221 (6):788-797.
[77]Hejna M,Pruckmayer M,Raderer M.The role of chemotherapy and radiation in the management of biliary cancer:a review of the literature[J].Eur J Cancer,1998, 34(7):977-986.
[78]Berr F.Photodynamic therapy for cholangiocarcinoma[J].Semin Liver Dis,2004,24(2):177-187.
[79]Zoepf T,Jakobs R,Rosenbaum A,et al.Photodynamic therapy with 5-aminolevulinic acid is not effective in bile duct cancer[J].Gastrointest Endosc, 2001,54(6):763-766.
2.Thomas H, Heaton ND. Late recurrence after surgery for cholangiocarcinoma: implications for follow-up? Hepatobiliary Pancreat Dis Int 2008;7:544-546
3.Ito Y, Tajima Y, Fujita F, et al. Solitary recurrence of hilar cholangiocarcinoma in a mediastinal lymph node two years after curative resection. World J Gastroenterol 2007; 13:2243-2246
4.Weber SM, Jarnagin WR, Klimstra D, et al. Intrahepatic cholangiocarcinoma: resectability, recurrence pattern, and outcomes. J Am Coll Surg 2001;193:384-391
5.Lang M, Henson R, Braconi C, Patel T. Epigallocatechin-gallate modulates chemotherapy-induced apoptosis in human cholangiocarcinoma cells. Liver Int 2009
6.Thongprasert S. The role of chemotherapy in cholangiocarcinoma. Ann Oncol 2005;16 Suppl2:ii93-96
7.陈华江,钟延强,贾连顺等.三氧化二砷白蛋白微球的理化特性及抗肿瘤活性检测.第二军医大学学报2007(5),644-646.
8.桑玉旗.三氧化二砷治疗多发性骨髓瘤的疗效及其作用机制.山东医药2007(25),40-41.
9.刘晓川,刘铁夫.缺氧时三氧化二砷对人肝癌细胞株bel-7402生长及凋亡的影响及机制.世界华人消化杂志2007(18),1983-1988.
10.黄建,陈康杰,张卧等.苦参碱抑制人大肠癌ht29细胞增殖及诱导凋亡作用与机制.中草药2007(8),1210-1214.
11.胡建莉,伍钢,肖兰.氧化苦参碱对人食管癌细胞株Eca109增殖及凋亡的影响.中国医院药学杂志2007(12),1662-1665.
12.Pushkarev VM, Starenki DV, Saenko VA, et al. Effects of low and high concentrations of antitumour drug taxol in anaplastic thyroid cancer cells. Exp Oncol 2009;31:16-21
13.Kumaran RS, Muthumary J, Hur BK. Isolation and identification of an anticancer drug, taxol from Phyllosticta tabernaemontanae, a leaf spot fungus of an angiosperm, Wrightia tinctoria. J Microbiol 2009;47:40-49
14.吕必华,张玲,朱长才等.姜黄素抑制HepG2细胞HDAC1活性及促进P21-(WAF1/CIP1)表达的研究.中国中药杂志2007(12),2051-2055.
15.邓刚,余建华,叶章群.姜黄素对雄激素非依赖性前列腺癌细胞Notch 1表达和分布的影响华中科技大学学报2007(6),740-743.
16.周永芹,韩莉.中药蜈蚣的研究进展.中药材2008(2),315-319.
17.赵志国,李军云,蒋晔等.蜈蚣酸性蛋白对急性心力衰竭大鼠心功能的影响.北京中医药大学学报2008(2),106-109.
18.曾红.蜈蚣中抗癌活性成分的提取.湖南中医杂志2004(5),57-58.
19.韩莉,周永芹,韩钰.·蜈蚣提取物诱导宫颈癌HeLa细胞凋亡及其机制的研究.时珍国医国药2007(9),2109-2111.
20.刘峰.蜈蚣的临床应用及其毒性研究.广西中医药1999(4),54-55.
21.任文华张宋周.少棘蜈蚣毒腺RACE cDNA文库的构建及β-actin基因的克隆与序列分析.动物学杂志2005(5),54-55
22.任文华,张双全,宋大祥等.少棘蜈蚣毒液溶血肽的分离纯化.动物学报2007(3),519-523
23.焦波,娄红祥,王东兴.蜈蚣提取液对小鼠精原细胞的作用.山东医科大学学报1999(4),358-362
24.司秋菊,王鑫国,白霞.蜈蚣对动脉粥样硬化家兔血液流变学的影响.中国老年学杂志2004；24(9)：831-833
25.杨培.中药：在美国的地位和fda政策.中国药科大学学报2007(5),385-390
26.唐健元,张磊,杜晓曦.国外上市植物药评价简介和对我国中药新药临床研究现状的思考.中药药理与临床2007(5),222-227
27.侯桂兰,芦柏震,王春雷.化疗药物所致消化系统毒副反应的中药防治.中华中医药学刊2008(8),1799-1801
28.张晓宇,吴雄志.中药减轻化疗毒性反应研究进展.辽宁中医药大学学报2007(6),187-189
29.许尤琪,丁蓉,张玉等.中药配合化疗治疗晚期非小细胞肺癌疗效观察.辽宁中医杂志2007(7),916-917
30.李蕾.中药多糖对环磷酰胺的增效减毒作用.中国热带医学2008(4),685-687
31.李凤云 陈张刘.中药制剂抗肿瘤作用的实验研究.中医药学报1999(5),57
32.李厚伟,张妍,许超千等.中药HB对喉癌Hep-2细胞的抑制作用及其机制研究.哈尔滨医科大学学报2001(4),55-56
33.刘国清,田秉漳,皮执民等.蜈蚣油性提取液对肝癌细胞增殖的影响.中国现代医学杂志2002(4),22-23
34.曲爱兵,赵维诚,梁良等.蜈蚣组织提取物抗肿瘤活性的初步研究.实用肿瘤学杂志2003(1),29-30
35.Yoshizaki T, Endo K, Ren Q, et al. Oncogenic role of Epstein-Barr virus-encoded small RNAs (EBERs) in nasopharyngeal carcinoma. Auris Nasus Larynx 2007;34:73-78
36.Li H, Ou X, Xiong J. Modified HPV16 E7/HSP70 DNA vaccine with high safety and enhanced cellular immunity represses murine lung metastatic tumors with downregulated expression of MHC class I molecules. Gynecol Oncol 2007;104:564-571
37.Kaneko T, Zhang Z, Mantellini MG, et al. Bcl-2 orchestrates a cross-talk between endothelial and tumor cells that promotes tumor growth. Cancer Res 2007;67:9685-9693
38.Lovas JG. Apoptosis in human epidermis:a postmortem study by light and electron microscopy. Australas J Dermatol 1986;27:1-5
39.Frey TG, Sun MG. Correlated light and electron microscopy illuminates the role of mitochondrial inner membrane remodeling during apoptosis. Biochim Biophys Acta 2008;1777:847-852
40.Kerr JF, Wyllie AH, Currie AR. Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972;26:239-257
41.Evangelou K, Bramis J, Peros I, et al. Electron microscopy evidence that cytoplasmic localization of the pl6(INK4A) "nuclear" cyclin-dependent kinase inhibitor (CKI) in tumor cells is specific and not an artifact. A study in non-small cell lung carcinomas. Biotech Histochem 2004;79:5-10
42.刘细平.蜈蚣提取液治疗肝细胞肝癌的实验研究.中国博士学位论文数据库(2007)。
43.王曙光,韩本立,段恒春,陈意生,彭志明.肝外胆管癌细胞系的建立.中华实验外科杂志1997(2),67-68
44.王曙光 陈李李.胆管癌细胞层粘连蛋白受体表达下调对蛋白水解酶尿激酶型纤维蛋白溶解酶原激酶mRNA表达的影响.中华医学杂志2004(19),62-64
45.Pernet P, Bruneel A, Baudin B, Vaubourdolle M. PHProteomicDB:a module for two-dimensional gel electrophoresis database creation on personal web sites. Genomics Proteomics Bioinformatics 2006;4:134-136
46.Pyndiah S, Lasserre JP, Menard A, et al. Two-dimensional blue native/SDS gel electrophoresis of multiprotein complexes from Helicobacter pylori. Mol Cell Proteomics 2007;6:193-206
47.Carrette O, Burkhard PR, Sanchez JC, Hochstrasser DF. State-of-the-art two-dimensional gel electrophoresis:a key tool of proteomics research. Nat Protoc 2006;1:812-823
48. Oh-Ishi M, Maeda T. Disease proteomics of high-molecular-mass proteins by two-dimensional gel electrophoresis with agarose gels in the first dimension (Agarose 2-DE). J Chromatogr B Analyt Technol Biomed Life Sci 2007;849:211-222
49.Zheng YZ, Foster LJ. Biochemical and proteomic approaches for the study of membrane microdomains. J Proteomics 2009;72:12-22
50.Wang X, Chen Y, Han QB, et al. Proteomic identification of molecular targets of gambogic acid:role of stathmin in hepatocellular carcinoma. Proteomics 2009;9:242-253
51.Sonck KA, Kint G, Schoofs G, et al. The proteome of Salmonella Typhimurium grown under in vivo-mimicking conditions. Proteomics 2009;9:565-579
52.Seeber B, Sammel MD, Fan X, et al. Proteomic analysis of serum yields six candidate proteins that are differentially regulated in a subset of women with endometriosis. Fertil Steril 2009
53.Wingren C, James P, Borrebaeck CA. Strategy for surveying the proteome using affinity proteomics and mass spectrometry. Proteomics 2009
54.Tian R, Wei LM, Qin RY, et al. Proteome analysis of human pancreatic ductal adenocarcinoma tissue using two-dimensional gel electrophoresis and tandem mass spectrometry for identification of disease-related proteins. Dig Dis Sci 2008;53:65-72
55.Remmerie N, Roef L, Van De Slijke E, et al. A bioanalytical method for the proteome wide display and analysis of protein complexes from whole plant cell lysates. Proteomics 2009;9:598-609
56.Doud MK, Schmidt MW, Hines D, et al. Rapid prefractionation of complex protein lysates with centrifugal membrane adsorber units improves the resolving power of 2D-PAGE-based proteome analysis. BMC Genomics 2004;5:25
57. Wu WW, Wang G, Baek SJ, Shen RF. Comparative study of three proteomic quantitative methods, DIGE, cICAT, and iTRAQ, using 2D gel-or LC-MALDI TOF/TOF. J Proteome Res 2006;5:651-658
58.Zhou J, Liang S, Fang L, et al. Quantitative Proteomic Analysis of HepG2 Cells Treated with Quercetin Suggests IQGAP1 Involved in Quercetin-Induced Regulation of Cell Proliferation and Migration. OMICS 2009
59.Schiess R, Mueller LN, Schmidt A, et al. Analysis of cell surface proteome changes via label-free, quantitative mass spectrometry. Mol Cell Proteomics 2008
60.Ishida Y, Yamashita K, Sasaki H, et al. Activation of complement system in adult T-cell leukemia (ATL) occurs mainly through lectin pathway:a serum proteomic approach using mass spectrometry. Cancer Lett 2008;271:167-177
61.Ahmad Y, Boisvert FM, Gregor P, Cobley A, Lamond AI. NOPdb:Nucleolar Proteome Database-2008 update. Nucleic Acids Res 2009;37:D181-184
62.Leung AK, Trinkle-Mulcahy L, Lam YW, et al. NOPdb:Nucleolar Proteome Database. Nucleic Acids Res 2006;34:D218-220
63.Fleissig Y, Deutsch O, Reichenberg E, et al. Different proteomic protein patterns in saliva of Sjogren's syndrome patients. Oral Dis 2009;15:61-68
64.Zhang L, Wang X, Peng X, et al. Immunoaffinity purification of plasma membrane with secondary antibody superparamagnetic beads for proteomic analysis. J Proteome Res 2007;6:34-43
65.Wright JC, Hubbard SJ. Recent developments in proteome informatics for mass spectrometry analysis. Comb Chem High Throughput Screen 2009; 12:194-202
66. Dani N, Stilla A, Marchegiani A, et al. Combining affinity purification by ADP-ribose-binding macro domains with mass spectrometry to define the mammalian ADP-ribosyl proteome. Proc Natl Acad Sci U S A 2009
67.Krauss S, Franke WW. Organization and sequence of the human gene encoding cytokeratin 8. Gene 1990;86:241-249
68.Chen N, Gong J, Chen X, et al. Cytokeratin expression in malignant melanoma:potential application of in-situ hybridization analysis of mRNA. Melanoma Res 2009;19:87-93
69.Ausch C, Buxhofer-Ausch V, Olszewski U, et al. Caspase-cleaved cytokeratin 18 fragment (M30) as marker of postoperative residual tumor load in colon cancer patients. Eur J Surg Oncol 2009
70.Xu W, Zhang MW, Huang J, et al. Correlation between CK18 gene and gastric carcinoma micrometastasis. World J Gastroenterol 2005;11:6530-6534
71.Yilmaz Y, Dolar E, Ulukaya E, et al. Elevated serum levels of caspase-cleaved cytokeratin 18 (CK18-Asp396) in patients with nonalcoholic steatohepatitis and chronic hepatitis C. Med Sci Monit 2009;15:CR189-193
72.Saussez S, Cludts S, Capouillez A, et al. Identification of matrix metalloproteinase-9 as an independent prognostic marker in laryngeal and hypopharyngeal cancer with opposite correlations to adhesion/growth-regulatory galectins-1 and-7. Int J Oncol 2009;34:433-439
73.Harjacek M, Diaz-Cano S, De Miguel M, et al. Expression of galectins-1 and-3 correlates with defective mononuclear cell apoptosis in patients with juvenile idiopathic arthritis. J Rheumatol 2001;28:1914-1922
74.Rabinovich GA, Gruppi A. Galectins as immunoregulators during infectious processes:from microbial invasion to the resolution of the disease. Parasite Immunol 2005;27:103-114
75.Salatino M, Croci DO, Bianco GA, et al. Galectin-1 as a potential therapeutic target in autoimmune disorders and cancer. Expert Opin Biol Ther 2008;8:45-57
76.Camby I, Le Mercier M, Lefranc F, Kiss R. Galectin-1:a small protein with major functions. Glycobiology 2006;16:137R-157R
77.Saussez S, Kiss R. Galectin-7. Cell Mol Life Sci 2006;63:686-697
78.Xiao D, Zhang L. Upregulation of Bax and Bcl-2 following prenatal cocaine exposure induces apoptosis in fetal rat brain. Int J Med Sci 2008;5:295-302
79. Zhang YJ, Dai Q, Wu SM, et al. Susceptibility for NSAIDs-induced apoptosis correlates to p53 gene status in gastric cancer cells. Cancer Invest 2008;26:868-877
80.Young KH, Xie Q, Zhou G, et al. Transformation of follicular lymphoma to precursor B-cell lymphoblastic lymphoma with c-myc gene rearrangement as a critical event. Am J Clin Pathol 2008;129:157-166
81.Demidchik V, Shang Z, Shin R, et al. Plant extracellular ATP signalling by plasma membrane NADPH oxidase and Ca(2+) channels. Plant J 2009
82.del Riego G, Casano LM, Martin M, Sabater B. Multiple phosphorylation sites in the beta subunit of thylakoid ATP synthase. Photosynth Res 2006;89:11-18
83.Cipriano DJ, Dunn SD. The role of the epsilon subunit in the Escherichia coli ATP synthase. The C-terminal domain is required for efficient energy coupling. J Biol Chem 2006;281:501-507
84.Eastman A, Rigas JR. Modulation of apoptosis signaling pathways and cell cycle regulation. Semin Oncol 1999;26:7-16; discussion 41-12
85.Tsujimoto Y, Cossman J, Jaffe E, Croce CM. Involvement of the bcl-2 gene in human follicular lymphoma. Science 1985;228:1440-1443
86.Suzuki A, Umezawa A, Sano M, Nozawa S, Hata J. Involvement of EAT/mcl-1, a bcl-2 related gene, in the apoptotic mechanisms underlying human placental development and maintenance. Placenta 2000;21:177-183
87.Sano M, Umezawa A, Suzuki A, et al. Involvement of EAT/mcl-1, an anti-apoptotic bcl-2-related gene, in murine embryogenesis and human development. Exp Cell Res 2000;259:127-139
88.Bakhshi A, Jensen JP, Goldman P, et al. Cloning the chromosomal breakpoint of t(14;18) human lymphomas:clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell 1985;41:899-906
89. O'Neill J, Manion M, Schwartz P, Hockenbery DM. Promises and challenges of targeting Bcl-2 anti-apoptotic proteins for cancer therapy. Biochim Biophys Acta 2004; 1705:43-51
90. Guo LL, Xiao S, Guo Y. Detection of bcl-2 and bax expression and bcl-2/JH fusion gene in intrahepatic cholangiocarcinoma. World J Gastroenterol 2004;10:3251-3254
91. Rao RV, Hermel E, Castro-Obregon S, et al. Coupling endoplasmic reticulum stress to the cell death program. Mechanism of caspase activation. J Biol Chem 2001;276:33869-33874
92.郭铁军,周振华,黄灼宏等.连休蜈蚣地龙汤对支原体肺炎患儿免疫功能的影响.新中医2007(1),19-21
93.曹勇,钟安朴,夏清华等.化瘀破癥胶囊干预荷瘤小鼠血清肿瘤坏死因子活性的变化.中国临床康复2006(23),118-120
94.Reynolds JL, Mahajan SD, Sykes D, Nair MP. Heroin-Induces Differential Protein Expression by Normal Human Astrocytes (NHA). Am J Infect Dis 2006;2:49-57
95. Wang WL, Yeh SF, Huang EY, et al. Mitochondrial anchoring of PKCalpha by PICK1 confers resistance to etoposide-induced apoptosis. Apoptosis 2007;12:1857-1871
96. Samaras V, Tsopanomichalou M, Stamatelli A, et al. Is there any potential link among caspase-8, p-p38 MAPK and bcl-2 in clear cell renal cell carcinomas? A comparative immunohistochemical analysis with clinical connotations. Diagn Pathol 2009;4:7
97. Wang M, Tsai BM, Reiger KM, Brown JW, Meldrum DR.17-beta-Estradiol decreases p38 MAPK-mediated myocardial inflammation and dysfunction following acute ischemia. J Mol Cell Cardiol 2006;40:205-212
98. Kuwabara I, Kuwabara Y, Yang RY, et al. Galectin-7 (PIG1) exhibits pro-apoptotic function through JNK activation and mitochondrial cytochrome c release. J Biol Chem 2002;277:3487-3497
99. Wei Y, Pattingre S, Sinha S, Bassik M, Levine B. JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell 2008;30:678-688
100.Yuan ZQ, Feldman RI, Sussman GE, et al. AKT2 inhibition of cisplatin-induced JNK/p38 and Bax activation by phosphorylation of ASK1: implication of AKT2 in chemoresistance. J Biol Chem 2003;278:23432-23440
101.Schafer B, Quispe J, Choudhary V, et al. Mitochondrial Outer Membrane Proteins Assist Bid in Bax-mediated Lipidic Pore Formation. Mol Biol Cell 2009
102.Youdim MB, Arraf Z. Prevention of MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) dopaminergic neurotoxicity in mice by chronic lithium: involvements of Bcl-2 and Bax. Neuropharmacology 2004;46:1130-1140
103.Eldering E, Mackus WJ, Derks IA, et al. Apoptosis via the B cell antigen receptor requires Bax translocation and involves mitochondrial depolarization, cytochrome C release, and caspase-9 activation. Eur J Immunol 2004;34:1950-1960
104.Isonishi S, Saitou M, Yasuda M, Tanaka T. Mitochondria in platinum resistant cells. Hum Cell 2001;14:203-210
105.Matsuyama S, Llopis J, Deveraux QL, Tsien RY, Reed JC. Changes in intramitochondrial and cytosolic pH:early events that modulate caspase activation during apoptosis. Nat Cell Biol 2000;2:318-325
106.Zhang B, Luo Y, Weng Q, et al. CPT21, a novel compound with anti-proliferative effect against gastric cancer cell SGC7901. Invest New Drugs 2008;26:517-524
107.Yang S, Hu S, Chen J, et al. Mechanism of hepatoprotection in proestrus female rats following trauma-hemorrhage:heme oxygenase-1-derived normalization of hepatic inflammatory responses. J Leukoc Biol 2009
108.Wu JN, Huang J, Yang J, et al. Caspase inhibition augmented oridonin-induced cell death in murine fibrosarcoma 1929 by enhancing reactive oxygen species generation. J Pharmacol Sci 2008; 108:32-39
109.Ferreira R, Neuparth MJ, Vitorino R, et al. Evidences of apoptosis during the early phases of soleus muscle atrophy in hindlimb suspended mice. Physiol Res 2008;57:601-611
110.Zurgil N, Afrimzon E, Shafran Y, et al. Lymphocyte resistance to lysophosphatidylcholine mediated apoptosis in atherosclerosis. Atherosclerosis 2007; 190:73-83
111.Zhang QY, Jiang M, Zhao CQ, et al. Apoptosis induced by one new podophyllotoxin glucoside in human carcinoma cells. Toxicology 2005;212:46-53
112.Zhang G, Matsumoto S, Hyon SH, et al. Polyphenol, an extract of green tea, increases culture recovery rates of isolated islets from nonhuman primate pancreata and marginal grade human pancreata. Cell Transplant 2004; 13:145-152
[1]Patel T, Singh P.Cholangiocarcinoma:emerging approaches to a challenging cancer[J].Curr Opin Gastroenterol,2007,23(3):317-323.
[2]Jasmine LH,Thomas RB,Faye TL,etal.Outcomes after resection of cholangio-cellular carcinoma[J]. Am J Surg,2004,187 (5):612-617.
[3]Dnes MJ,Erlich R, Matthew JO,Rodrigo E.A review and update on cholangiocarcinoma[J].Oncol,2004,66(3):167-179.
[4]Berthiaume EP,Wands J.The molecular pathogenesis of cholangiocarcinoma [J]. Semin Liver Dis,2004,24(2):127-137.
[5]Ito Y, Takeda T, Sasaki Y, et al.Bcl-2 expression in cholangiocellular carcinoma is inversely correlated with biologically aggressive phenotypes[J]. Oncology,2000,59(1):63-67.
[6]Li SM, Yao SK, Yamamura N, et al.Expression of Bcl-2 and Bax in extrahepatic biliary tract carcinoma and dysplasia [J].World Jgastroenterol,2003,9(11): 2579-2582.
[7]Su WC, Shiesh SC, Liu HS, et al.Expression of oncogene productsHER2 /Neu and Ras and fibrosis-related growth factors bFGF, TGF-beta, and PDGF in bile from biliarymalignancies-and inflammatory disorders[J].Dig Dis Sci,2001,46(7): 1387-1392.
[8]Ukita Y, KatoM, Terada T. Gene amplification and mRNA and protein over-expression of c-erbB-2 (HER-2/neu) in human intrahepatic cholangiocarcinoma as detected by fluorescence in situ hybridization, in situ hybridization, and immunohistochemistry[J]. J Hepato,l 2002,36(6):780-785.
[9]Aishima SI, Taguchi KI, Sugimachi K, et al.c-erbB-2 and c-Met expression relates to cholangiocarcinogenesis and progression of intrahepatic cholan-giocarcinoma [J].Histopathology,2002,40(3):269-278.
[10]BobergKM, SchrumpfE, BergquistA, eta.l Cholangiocarcinomain primary sclerosing cholangitis:K-rasmutations and Tp53 dysfunction are implicated in the neoplastic development[J]. Hepatol,2000,32(3):374-380.
[11]Isa T,Tomita S,NakachiA,et al.Analysis of microsatellite instability, K-ras genemutation and p53 protein overexpression in intrahepatic cholangio-carcinoma[J]. Hepatogastroenterology,2002,49(45):604-608.
[12]Voravud N,Foster CS,Gilbertson JA,et al,Oncogene expressionin cholangio-carcinoma and in normal hepatic development[J].Hum Pathol,1989,20(12): 1163-1168.
[13]Limpaiboon T, Sripa B,Wongkham S, et al.Anti-p53 antibodiesand p53 protein expression in cholangiocarcinoma[J]. Hepatogastroenterology,2004,51 (55):25-28.
[14]Wang Y, Yamaguchi Y, Watanabe H, et al,Usefulness of p53 gene mutations in the supernatant of bile for diagnosis of biliary tract carcinoma: comparison with K-rasmutation[J]. Gastroenterol,2002,37 (10):831-839.
[15]Argani P, Shaukat A,Kaushal M, et al.Differing rates of loss of DPC4 expression and of p53 overexpression among carcinomas of the proximal and distal bile ducts[J].Cancer,2001,91(7):1332-1341.
[16]Tang Z, Zou S, Hao Y, et al,Frequency of loss expression of the DPC4 protein in various locations of biliary tract carcinoma[J]. ZhonghuaYu FangYiXue Za Zhi,2002,36(7):481-484.
[17]Fujii K,Yasui W,Shimamoto F,et al.Immunohistochemical analysis of nm23 gene product in human gallbladder carcinomas[J]. VirchowsArch,1995,426(4): 355-359.
[18]Benckert C,Jonas S,Cramer T,et al.Transforming growth factor beta 1 stimulates vascular endothelial growth factor gene transcription in human cholangiocellular carcinoma cells[J]. CancerRes,2003,63(5):1083-1092.
[19]Kawahara N,Ono M,Taguchi K,et al.Enhanced expression of thrombospondin-1 and hypovascularity in human cholangiocarcinoma[J]. Hepatology, 1998,28(6):1512-1517.
[20]Ogasawara S,Yano H,HigakiK,et al.Expression of angiogeni factors, basic fibroblast growth factor and vascular endothelia growth factor, in human biliary tract carcinoma cell lines[J]. Hepatol Res,2001,20(1):97-113.
[21]Xiao M,Zhou N X,Huang ZQ,et al.The ratio of MMP-2 tTIMP-2 in hilar cholangiocarcinoma:a semi-quantitative study [J].Hepatobiliary Pancreat Dis Int, 2004,3(4):599-602.
[22]Miwa S,Miyagawa S,Soeda J,et al.Matrixmetalloproteinase expression and biologic aggressiveness of cholangiocellular carcinoma [J].Cancer,2002,94(2): 428-434.
[23]Zheng XH,Wang XG,Yan XC,et al.Expression and significance of integrin avβ3 in human bile ductcarcinoma[J].Acta Academae Medicinae Militaris Tertiae,2005,27(12):1276-1278.
[24]Tsuchikawa T,Kondo S,Hirano S,et al.Long-term survival after curative left hepatectomy formucin-producing cholangiocarcinoma:report of a case[J].Surg Today,2005,35(3):256-258.
[25]Higashi M,Yonezawa S,Ho JJ,et al.Expression of MUC1 and MUC2 mucin antigens in intrahepatic bile duct tumors:its relationship with a new morphological classification of cholangiocarcinom[J]. Hepatology,1999,30(6):1347-1355.
[26]Bjornsson E,Kilander A,Olsson R.CA19-9 and CEA are unrelable markers for cholangiocarcinoma in patients with primary sclerosing cholangitis[J].Liver,1999, 19(6):501-508.
[27]Okami J,Dohno K,Sakon M,et al.Genetic detection for micrometastasis in lymph node of biliary tract carcinoma[J].Clin Cance Res,2000,6(6):2326-2332.
[28]Patel AH,Harnois DM,Klee GG,et al.The utility of CA19-9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis[J].Am J Gastroenterol,2000,95 (1):204-207.
[29]Ramage JK,Donaghy A,Farrant JM,et al.Serum tumor markers for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis[J]. Gastroente-rology,1995,108(3):865-869.
[30]Watanabe M,Chigusa M,Takahashi H,et al.High level of Cal9-9,CA50,and CEA-producible human cholangiocarcinoma cell line changes in the secretion ratios in vitro or in vivo[J].In Vitro Cell Dev Biol Anim,2000,36(2):104-109.
[31]Pasanen PA,Eskelinen M,Partanen K,et al.Clinical value of serum tumour markers CEA, CA 50 and CA242 in the distinction between malignant versus benign diseases causing jaundice and cholestasis;results from a prospective study[J]. Anticancer Res,1992,12(5):1687-1693.
[32]Enjoji M,Yamaguchi K,Nakamuta M,etal.Movement of a novel serum tumour marker, RCAS1, in patients with biliary diseases[J].Dig Liver Dis,2004,36(9): 622-627.
[33]Watanabe H,Enjoji M,Nakashima M,et al.Clinical significance of serum RCAS1 levels detected by monoclonal antibody 22-1-1 in patients with cholangiocellular carcinoma[J].Hepatol,2003,39(4):559-563.
[34]Suzuoki M,Hida Y,Miyamoto M,et al.RCAS1 expression as aprognostic factor after curative surgery for extrahepatic bile duct carcinoma[J].Ann Surg Oncol,2002,9(4):388-393.
[35]Kanno N,Glaser S,Chowdhury U,et al.Gastrin inhibits cholangiocarcinoma growth through increased apoptosis by activation of Ca2+-dependent protein kinase C-alpha[J].Hepatol,2001,34(2):284-291.
[36]Caplin M,Khan K,Savage K,et al.Expression and processing of gastrin in hepatocellular carcinoma, fibrolamellar carcinoma and cholangiocarcinoma[J]. Hepatol,1999,30(3):519-526.
[37]Zhao B,Zhao H,Zhao N,et al.Cholangiocarcinoma cells express somatostatin receptor subtype 2 and respond to octreotide treatment[J].Hepatobiliary Pancreat Surg,2002 9(4):497-502.
[38]Lie-A-Ling M,Bakker CT,Deurholt T,et al.Selection of tumour specific promoters for adenoviral gene therapy of cholangiocarcinoma[J].Hepatol,2006, 44(1):126-133.
[39]Itoi T,Shinohara Y,Takeda K,et al.Detection of telomerase reverse transcriptase mRNA in biopsy specimens and bile for diagnosis of biliary tract cancers[J].Int J Mol Med,2001,7(3):281-287.
[40]Washburn WK,Lewis WD,Jenkins RL.Aggressive surgical resection for cholangiocarcinoma[J]. Arch Surg,1995,130(3):270-276.
[41]Tangkijvanich P,Thong-ngam D,Theam-boonlers A, et al.Diagnostic role of serum interleukin 6 and CA19-9 in patients with cholangiocarcinoma[J]. Hepatogastroenterology,2004,51 (55):15-19.
[42]Chen CY,Lin XZ,WuHC,et al.The value of biliary amylase and Hepatocarcinoma-Intestine-Pancreas/Pancreatitis-associated Protein I (HIP/PAP-I) in diagnosing biliary malignancies [J]. Clin Biochem,2005,38(6):520-525.
[43]Kipp BR,Stadheim LM,HallingSA,et al.Acomparison of routine cytology and fluorescence in situ hybridization for the detection bile duct strictures[J].Am J Gastroenterol,2004,99(9):1675-1681.
[44]Poneros JM,Tearney GJ,Shiskov M,et al.Optical coherence tomography of the biliary tree during ERCP[J].Gastrointest Endosc,2002,55(1):84-88.
[45]Xu HX, Lu MD, Liu GJ,et al.Imaging of peripheral cholangiocarcinoma with low-mechanical index contrast-enhanced sonography and SonoVue:initial experience [J]. Ultrasound Med,2006,25(1):23-33.
[46]Sakata J, Shirai Y,Wakai T, et al.Catheter tract implantation metastases associated with percutaneous biliary drainage for extrahepatic cholangiocarcinoma[J]. World J Gastroenterol,2005,11(44):7024-7027.
[47]Christensen M,Matzen P, Schulze S, et al.Complications of ERCP:a prospective study[J].Gastrointest Endosc,2004,60 (5):721-731.
[48]Kim HJ, Kim AY, Hong SS, et al.Biliary ductal evaluation of hilar cholangiocarcinoma:three-dimensional direct multi-detector row CT cholangiographic findings versus surgical and pathologic results feasibility study[J].Radiology,2006, 238(1):300-308.
[49]Stroszczynski C,Hunerbein M.Malignant biliary obstruction:value of imaging findings[J]. Abdom Imaging,2005,30 (3):314-323.
[50]Olnes MJ,Erlich R.A review and update on cholangiocarcinoma[J]. Oncology,2004,66(3):167-179.
[51]Khan SA,Thomas HC,Davidson BR,et al.Cholangiocarcinoma [J].Lancet,2005,366(9493):1303-1314.
[52]Reddy SB,Patel T.Current approaches to the diagnosis and treatment of cholangiocarcinoma [J].Curr Gastroenterol Rep,2006,8(1):30-37.
[53]Nakeeb A, Tran KQ, Black MJ,et al.Improved survival in resected biliary malignancies [J].Surgery,2002,132(4):555-563.
[54]杨维良,张东伟,佟佰峰,等。肝门部胆管癌165例的诊断与外科治疗。中华肝胆外科杂志。2006,12(8)：512-514。
[55]黎介寿,吴孟超,黄志强.普通外科手术学[M].北京：人民军医出版社,2005：728-732.
[56]Kawasaki S,Imamura H,Kobayashi A,et al.Results of surgical resection for patients with hilar bile duct cancer:application of extended hepatectomy after biliary drainage and hemihepatic portal vein embolization[J].Ann Surg,2003,238(1):84-92.
[57]Ortner ME,Caca K,BerrF,et al.Successful photodynamic therapy for non resectable cholangiocarcinoma:a randomized prospective study[J].Gastroentero-logy,2003,125(5):1355-1363.
[58]Varotti G,Gondolesi GE,Roayaie S,et al.Combined adult-to-adult living donor right lobe liver transplantation and pancreatoduodenectomy for distal bile duct adenocarcinoma in a patient with primary sclerosing cholangitis[J].J Am Coll Surg,2003,197(5):765-769.
[59]詹文华,何晓顺,朱晓峰,等.亚洲首例胰腺癌并肝脏多发转移患者上腹部器官簇移植成功[J].中华胃肠外科杂志,2004,7(4)：335.
[60]Seyama Y,Makuuchi M.Current surgical treatment for bile duct cancer.World J Gastroenterol,2007,13(10):1505-1515.
[61]McMasters KM,Tuttle TM,Leach SD,et al.Neoadjuvant chemoradiation for extrahepatic cholangiocarcinoma[J]. Am J Surg,1997,174(6):605-608.
[62]Wiedmann M,Caca K,Berr F,et al.Neoadjuvant photodynamic therapy as a new approach to treating hilar cholangiocarcinoma:aphase II pilot study[J].Cancer, 2003,97(11):2783-2790.
[63]Khan SA,Davidson BR,GoldinR, etal.Guidelines for the diagnosis and treatment of cholangiocarcinoma:consensus document[J].Gut,2002,51 (Suppl6): VI1-9.
[64]Mittal B,Deutsch M,Iwatsuki S.Primary cancers of extrahepatic biliary passages[J]. Int J Radiat Oncol Biol Phys,1985,11(4):849-854.
[65]Glimelius B,Hoffman K,Sjoden PO,et al.Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cance[J].Ann Oncol,1996,7(6): 593-600.
[66]Thongprasert S.The role of chemotherapy in cholangiocarcinoma[J]. Ann Oncol,2005,16 (Suppl2):ii93-96.
[67]Choi CW,Choi IK,Seo JH,et al.Effects of 5-fluorouracil and leucovorin in the treatment of pancreatic-biliary tract adenocarcinomas[J]. Am J Clin Oncol,2000, 23(4):425-428.
[68]Ducreux M,Rougier P,Fandi A,et al.Effective treatment of advanced biliary tract carcinoma using 5-fluorouracil continuous infusion with cisplatin[J].Ann Oncol, 1998,9(6):653-656.
[69]Lee MA,Woo IS,Kang JH,et al.Epirubicin,cisplatin,and protracted infusion of 5-FU (ECF) in advanced intrahepatic cholangiocarcinoma [J].Cancer Res Clin Oncol,2004,130 (6):346-350.
[70]Patt YZ,Hassan MM,Aguayo A,et al.Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma, and gall bladder carcinoma[J]. Cancer,2004,101(3):578-586.
[71]Dingle BH,Rumble RB,BrouwersMC,et al.The role of gemcitabine in the treatment of cholangiocarcinoma and gallbladder cancer:a systematic review[J]. Can J Gastroenterol,2005,19(12):711-716.
[72]Andre T,Tournigand C,Rosmorduc O,et al.Gemcitabine combined with oxaliplatin (GEMOX) in advanced biliary tractadenocarcinoma:a GERCOR study[J].Ann Oncol,2004,15(9):1339-1343.
[73]Alberts SR,Fishkin PA,Burgart LJ,et al.CPT-11 for bile-duct and gallbladder carcinoma:a phase Ⅱ North Central Cancer Treatment Group (NCCTG) study[J]. Int J Gastrointest Cancer,2002,32(2-3):107-114.
[74]JonesDV,LozanoR,HoqueA,et al.Phase Ⅱ study of paclitaxe therapy for unresectable biliary tree carcinomas[J]. Clin Oncol,1996,14(8):2306-2310.
[75]Papakostas P,Kouroussis C,Androulakis N,et al.First-line chemotherapy with docetaxel for unresectable or metastatic carcinoma of the biliary tract. A multicentre phase Ⅱ study[J].Eur J Cancer,2001,37(15):1833-1838.
[76]Pitt HA,Nakeeb A,Abrams RA,et al.Perihilar cholangiocarcinoma. Postoperative radiotherapy does not improve survival[J]. AnnSurg,1995,221 (6):788-797.
[77]Hejna M,Pruckmayer M,Raderer M.The role of chemotherapy and radiation in the management of biliary cancer:a review of the literature[J].Eur J Cancer,1998, 34(7):977-986.
[78]Berr F.Photodynamic therapy for cholangiocarcinoma[J].Semin Liver Dis,2004,24(2):177-187.
[79]Zoepf T,Jakobs R,Rosenbaum A,et al.Photodynamic therapy with 5-aminolevulinic acid is not effective in bile duct cancer[J].Gastrointest Endosc, 2001,54(6):763-766.