清胰化积方对人胰腺癌CFPAC-1裸鼠移植瘤的抑瘤作用及其机理研究
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摘要
目的
了解清胰化积方对人胰腺癌CFPAC-1裸鼠移植瘤的抑瘤作用,从细胞因子、细胞周期、癌相关基因表达层面探索其抑瘤机理。
方法
1.清胰化积方对人胰腺癌CFPAC-1裸鼠移植瘤的抑瘤作用研究
采用荷CFPAC-1人胰腺癌裸小鼠模型,随机分组后,以不同剂量的清胰化积方及化疗药物进行干预,观察药物的体内抑瘤作用。
2.清胰化积中药对人胰腺癌CFPAC-1裸鼠移植瘤的抑瘤机理探讨
2.1采用ELISA法检测裸鼠血清细胞因子VEGF、TNF-α、sVCAM-1、TGF-β1、IL-6和IL-8的表达;
2.2用流式细胞术检测清胰化积方对CFPAC-1裸鼠移植瘤细胞周期的影响;
2.3用普通RT-PCR及qPCR法检测EphB2的表达,并针对目标基因EphB2构建慢病毒干扰载体,进行RNA干扰等深入研究。
结果
1.清胰化积方对人胰腺癌CFPAC-1裸鼠移植瘤的抑瘤作用研究
清胰化积方对人胰腺癌CFPAC-1细胞株体内生长有一定的抑制作用,中药组瘤重低于对照组(p＜0.05),清胰化积方各剂量组的抑瘤率约32～34%。
2.清胰化积中药对人胰腺癌CFPAC-1裸鼠移植瘤的抑瘤机理探讨
2.1清胰化积方对人胰腺癌CFPAC-1裸鼠血清VEGF、TNF-α、sVCAM-1、TGF-β1、IL-6和IL-8表达水平的影响:清胰化积方治疗后相应组裸鼠血清TNF-α、IL-6、IL-8水平显著低于对照组(p＜0.05),且与瘤重呈正相关。各组裸鼠血清VEGF、TGF-β1、和sVCAM-1表达水平之间无显著性差异(P＞0.05)。
2.2清胰化积方对人胰腺癌CFPAC-1裸鼠移植瘤细胞周期的影响:清胰化积方治疗后CFPAC-1细胞出现S期阻滞,S期细胞比例明显高于对照组,G_2/M期细胞比例低于对照组(P＜0.01)。各组间的凋亡率则无显著性差异(P＞0.05)。
2.3清胰化积方对人胰腺癌CFPAC-1裸鼠移植瘤EphB2表达的影响:清胰化积方组EphB2表达水平与对照组相比较有两倍以上的上调。针对CFPAC-1细胞系进行EphB2 RNA干扰后,流式细胞分析提示EphB2下调可以抑制CFPAC-1细胞的凋亡。
结论
1.清胰化积方对人胰腺癌CFPAC-1体内生长有明显的抑制作用,主要表现为诱导胰腺癌细胞发生坏死。
2.清胰化积方抑瘤作用的机理,可能与减少人胰腺癌CFPAC-1荷瘤裸鼠血清细胞因子含量、诱导肿瘤细胞周期的S期阻滞及上调EphB2基因表达有关。
Objectives
The aim of this study was to investigate the inhibitory effects of QYHJ decoction on human pancreatic cancer cell line CFPAC-1 in nude mice,and its influence on extracellular factors,cell cycle,cancer related genes and signal transduction.
Materials and Methods
1.Reaseach on Inhibitory effects of QYHJ decoction on experimental pancreatic cancer cell line CFPAC-1 in nude mice
Human pancreatic cancer cell line CFPAC-1 burdened nude mice were randomized to receive QYHJ decoction at different doses and oral chemotherapeutics.Inhibitory rates of tumor growth in vivo were calculated.
2.Research on mechanism of inhibitory effects of QYHJ decoction on experimental pancreatic cancer cell line CFPAC-1 in nude mice
2.1 ELISA was used to detect serum extracellular factors such as VEGF、TNF-α、sVCAM-1、TGF-β1、IL-6 and IL-8 in nude mice.
2.2 Flow cytometry technique was used to analyze transplanted tumors of nude mice. RT-PCR and quantitative PCR were used to amplify the gene of EphB2. Lentivirus interference vector was constructed to knockdown the targeted gene EphB2 for further study.
Results
1.Inhibitory effects of QYHJ decoction on experimental pancreatic cancer cell line CFPAC-1 in nude mice
QYHJ decoction could inhibit the growth of human pancreatic cancer cell line CFPAC-1 in vivo.Tumor weight in the QYHJ groups was significantly lower than that in control group(P＜0.05).Inhibiting rate of tumor growth varied from 33 to 38%in different dose of QYHJ groups.
2.mechanism of inhibitory effects of QYHJ decoction on experimental pancreatic cancer cell line CFPAC-1 in nude mice
2.1 The expression of serum extracellular factors such as VEGF、TNF-α、sVCAM-1、TGF-β1、IL-6 and IL-8 in nude mice:The serum level of TNF-α, IL-6 and IL-8 in the QYHJ-treated group was significantly lower than that in the control group(P＜0.05),and these above factors had a negative correlation with the inhibitory rate.There were no significant difference among each groups for the serum level of VEGF、TGF-β1 and sVCAM-1(P＞0.05).
2.2 Results of cytometry analyses in each group:S-phase arrest was detected in the tumors of QYHJ-treated groups:The proportion of cells in S phase was higher, and which in G2/M phase was lower accordingly,when compared with the control group(P＜0.05).
2.3 The expression of EphB2 in transplanted tumor of each group:The expression level of EphB2 in QYHJ-treated group was 2-fold or more elevated than that in the control group.Cytometry analyses revealed that downregulation of EphB2 may promote apoptosis in the CFPAC-1 cell line.
Conclusions
1.QYHJ decoction may remarkablely inhibit the growth of human pancreatic cancer cell line CFPAC-1 in vivo,the pattern of manifestation is to induce the pancreatic cancer cells to be necrosis.
2.The mechanism of inhibitory effects of QYHJ decoction may correlate with downregulation of the serum level of extracellular factors,S-phase arrest in the cell cycle induced by QYHJ decoction,and upregulation of EphB2.
了解清胰化积方对人胰腺癌CFPAC-1裸鼠移植瘤的抑瘤作用,从细胞因子、细胞周期、癌相关基因表达层面探索其抑瘤机理。
方法
1.清胰化积方对人胰腺癌CFPAC-1裸鼠移植瘤的抑瘤作用研究
采用荷CFPAC-1人胰腺癌裸小鼠模型,随机分组后,以不同剂量的清胰化积方及化疗药物进行干预,观察药物的体内抑瘤作用。
2.清胰化积中药对人胰腺癌CFPAC-1裸鼠移植瘤的抑瘤机理探讨
2.1采用ELISA法检测裸鼠血清细胞因子VEGF、TNF-α、sVCAM-1、TGF-β1、IL-6和IL-8的表达;
2.2用流式细胞术检测清胰化积方对CFPAC-1裸鼠移植瘤细胞周期的影响;
2.3用普通RT-PCR及qPCR法检测EphB2的表达,并针对目标基因EphB2构建慢病毒干扰载体,进行RNA干扰等深入研究。
结果
1.清胰化积方对人胰腺癌CFPAC-1裸鼠移植瘤的抑瘤作用研究
清胰化积方对人胰腺癌CFPAC-1细胞株体内生长有一定的抑制作用,中药组瘤重低于对照组(p＜0.05),清胰化积方各剂量组的抑瘤率约32～34%。
2.清胰化积中药对人胰腺癌CFPAC-1裸鼠移植瘤的抑瘤机理探讨
2.1清胰化积方对人胰腺癌CFPAC-1裸鼠血清VEGF、TNF-α、sVCAM-1、TGF-β1、IL-6和IL-8表达水平的影响:清胰化积方治疗后相应组裸鼠血清TNF-α、IL-6、IL-8水平显著低于对照组(p＜0.05),且与瘤重呈正相关。各组裸鼠血清VEGF、TGF-β1、和sVCAM-1表达水平之间无显著性差异(P＞0.05)。
2.2清胰化积方对人胰腺癌CFPAC-1裸鼠移植瘤细胞周期的影响:清胰化积方治疗后CFPAC-1细胞出现S期阻滞,S期细胞比例明显高于对照组,G_2/M期细胞比例低于对照组(P＜0.01)。各组间的凋亡率则无显著性差异(P＞0.05)。
2.3清胰化积方对人胰腺癌CFPAC-1裸鼠移植瘤EphB2表达的影响:清胰化积方组EphB2表达水平与对照组相比较有两倍以上的上调。针对CFPAC-1细胞系进行EphB2 RNA干扰后,流式细胞分析提示EphB2下调可以抑制CFPAC-1细胞的凋亡。
结论
1.清胰化积方对人胰腺癌CFPAC-1体内生长有明显的抑制作用,主要表现为诱导胰腺癌细胞发生坏死。
2.清胰化积方抑瘤作用的机理,可能与减少人胰腺癌CFPAC-1荷瘤裸鼠血清细胞因子含量、诱导肿瘤细胞周期的S期阻滞及上调EphB2基因表达有关。
Objectives
The aim of this study was to investigate the inhibitory effects of QYHJ decoction on human pancreatic cancer cell line CFPAC-1 in nude mice,and its influence on extracellular factors,cell cycle,cancer related genes and signal transduction.
Materials and Methods
1.Reaseach on Inhibitory effects of QYHJ decoction on experimental pancreatic cancer cell line CFPAC-1 in nude mice
Human pancreatic cancer cell line CFPAC-1 burdened nude mice were randomized to receive QYHJ decoction at different doses and oral chemotherapeutics.Inhibitory rates of tumor growth in vivo were calculated.
2.Research on mechanism of inhibitory effects of QYHJ decoction on experimental pancreatic cancer cell line CFPAC-1 in nude mice
2.1 ELISA was used to detect serum extracellular factors such as VEGF、TNF-α、sVCAM-1、TGF-β1、IL-6 and IL-8 in nude mice.
2.2 Flow cytometry technique was used to analyze transplanted tumors of nude mice. RT-PCR and quantitative PCR were used to amplify the gene of EphB2. Lentivirus interference vector was constructed to knockdown the targeted gene EphB2 for further study.
Results
1.Inhibitory effects of QYHJ decoction on experimental pancreatic cancer cell line CFPAC-1 in nude mice
QYHJ decoction could inhibit the growth of human pancreatic cancer cell line CFPAC-1 in vivo.Tumor weight in the QYHJ groups was significantly lower than that in control group(P＜0.05).Inhibiting rate of tumor growth varied from 33 to 38%in different dose of QYHJ groups.
2.mechanism of inhibitory effects of QYHJ decoction on experimental pancreatic cancer cell line CFPAC-1 in nude mice
2.1 The expression of serum extracellular factors such as VEGF、TNF-α、sVCAM-1、TGF-β1、IL-6 and IL-8 in nude mice:The serum level of TNF-α, IL-6 and IL-8 in the QYHJ-treated group was significantly lower than that in the control group(P＜0.05),and these above factors had a negative correlation with the inhibitory rate.There were no significant difference among each groups for the serum level of VEGF、TGF-β1 and sVCAM-1(P＞0.05).
2.2 Results of cytometry analyses in each group:S-phase arrest was detected in the tumors of QYHJ-treated groups:The proportion of cells in S phase was higher, and which in G2/M phase was lower accordingly,when compared with the control group(P＜0.05).
2.3 The expression of EphB2 in transplanted tumor of each group:The expression level of EphB2 in QYHJ-treated group was 2-fold or more elevated than that in the control group.Cytometry analyses revealed that downregulation of EphB2 may promote apoptosis in the CFPAC-1 cell line.
Conclusions
1.QYHJ decoction may remarkablely inhibit the growth of human pancreatic cancer cell line CFPAC-1 in vivo,the pattern of manifestation is to induce the pancreatic cancer cells to be necrosis.
2.The mechanism of inhibitory effects of QYHJ decoction may correlate with downregulation of the serum level of extracellular factors,S-phase arrest in the cell cycle induced by QYHJ decoction,and upregulation of EphB2.
引文
[1]Jemal A,Siegel R,Ward E,et al.Cancer Statistics,2008.CA Cancer J Clin.2008;58:71-96.
[2]上海市疾病预防控制中心.2004年上海市市区恶性肿瘤发病率.肿瘤,2007;27(7):594.
[3]Kleeff J,Michalski C,Friess H,et al.Pancreatic cancer:from bench to 5-year survival.Pancreas.2006;33(2):111-8.
[4]Oettle H,Post S,Neuhaus P,et al.Adjuvant chemotherapy with gemcitabine vs.observation in patients undergoing curative-intent resection of pancreatic cancer:a randomized controlled trial.JAMA.2007;297:267-277.
[5]Cameron JL,Riall TS,Coleman J,et al.One thousand consecutive pancreatico- duodenectomies.Ann Surg.2006;144:10-15.
[6]Nishimura Y,Hosotani R,Shibamoto Y,et al.External and intraoperative radiotherapy for resectable and unresectable pancreatic cancer:analysis of survival rates and complications.Int J Radiat Oncol Biol Phys.1997.39:39-49.
[7]Millikan KW,Deziel DJ,Silverstein JC,et al.Prognostic factors associated with resectable adenocarcinoma of the head of the pancreas.Am Surg.1999.65:618-623;discussion 623-614.
[8]Fine RL,Fogelman DR,Schreibman SM,et al.The gemcitabine,docetaxel,and capecitabine (GTX) regimen for metastatic pancreatic cancer:a retrospective analysis.Cancer Chemother Pharmacol,2008;61(1):167-175.
[9]Okusaka T,Ishii H,Funakoshi A,et al.A phase Ⅰ/Ⅱ study of combination chemotherapy with gemcitabine and 5-fluorouracil for advanced pancreatic cancer.Jpn J Clin Oncol.2006;36(9):557-63.
[10]谢德荣,梁汉霖,杨琼等.吉西他滨联合卡培他滨一线治疗晚期胰腺癌的Meta分析.世界华人消化杂志,2007;15(16):1868-1871.
[I1]Ulrich-Pur H,Raderer M,Kornek GV,et al.Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced adenocarcinoma.Br J Cancer,2003;88:1180-1184.
[12]Reni M,Pasetto L,Aprile G,et al.Raltitrexed-eloxatin salvage chemotherapy in gemcitabine-resistant metastatic pancreatic cancer.Br J Cancer,2006;94(6):785-791.
[13]Hazard L.The role of radiation therapy in pancreas cancer.Gastrointest Cancer Res.2009;3(1):20-8.
[14]Huguet F,Girard N,Seblain-El Guerche C,et al.Chemoradiotherapy in the Management of Locally Advanced Pancreatic Carcinoma:A Qualitative Systematic Review.J Clin Oncol.2009.[Epub ahead of print]
[15]Timke C,Debus JP.The role of radiation therapy in treatment of pancreatic cancer from the viewpoint of radio-oncologists.Radiologe.2009;49(2):149-53.
[16]Dubinsky TJ,Cuevas C,Dighe MK,et al.High-intensity focused ultrasound:current potential and oncologic applications.AJR Am J Roentgenol.2008;190(1):191-9.
[17]Moore MJ,Goldstein D,Hamm J,et al.Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer:a phase Ⅲ trial of the National Cancer Institute of Canada Clinical Trials Group.J Clin Oncol.2007.25:1960-1966.
[18]Kindler HL,Friberg G,Singh DA,et al.Phase Ⅱ trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer.J Clin Oncol.2005.23:8033-8040.
[19]Xiong HQ,Rosenberg A,LoBuglio A,et al.Cetuximab,a monoclonal antibody targeting the epidermal growth factor receptor,in combination with gemcitabine for advanced pancreatic cancer:a multicenter phase Ⅱ Trial.J Clin Oncol.2004.22:2610-2616.
[20]No listed authors.Gemcitabine plus bevacizumab no better than gemcitabine alone in clinical study of 600 patients with pancreatic cancer.Cancer Biol Ther.2007;6:137.
[21]Cascinu S,Berardi R,Labianca R,et al.Cetuximab plus gemcitabine and cisplatin compared with gemcitabine and cisplatin alone in patients with advanced pancreatic cancer:a randomised,multicentre,phase Ⅱ trial,Lancet Oncol.2008;9(1):39-44.
[22]沈晔华,刘鲁明,陈震等.中药联合化疗治疗晚期胰腺癌32例临床研究.中医杂志2006,47(2):115-117.
[23]沈晔华,刘鲁明,孟志强,等.清胰化积方为主综合治疗晚期胰腺癌64例生存分析.中医杂志.2009.50(1):39-42.
[24]沈晔华,刘鲁明,沈瑾,等.清胰消积方对实验性胰腺癌体内生长和细胞周期的影响.中国中医基础医学杂志.2006.12(2):97-99.
[25]沈晔华,刘鲁明,陆燕.清胰消积中药对实验性胰腺癌基因表达的影响.中国癌症杂志.2005.15(5):454-461.
[26]傅洁,刘鲁明,沈瑾,等.清胰化积方联合健择对SW1990抑瘤及逆转MDR作用观察.中国中医基础医学杂志.2007.13(4):289-291.
[27]陈培丰,刘鲁明.清胰消积方抑瘤效应及诱导肿瘤细胞凋亡作用的研究.中国中医药科技.2000,7(3):145-146.
[28]陈培丰,刘鲁明.清胰消积方抑制肝癌腹水和肺转移作用的实验研究.浙江中西医结合杂志,2000,10(6):340-341.
[29]Schoumacher RA,Ram J,Iannuzzi MC,et al.A cystic fibrosis pancreatic adenocarcinoma cell line.Proc Natl Acad Sci USA.1990;87(10):4012-6.
[30]余泽前,周家华,胡亮,等.人胰腺癌细胞CFPAC-1裸小鼠原位移植瘤模型的建立.东南大学学报(医学版).2008,27(1):27-30.
[1]刘鲁明.胰腺癌的中医病因病机与辨病论治.中西医结合学报.2008,6(12):1297-1299.
[2]沈晔华,刘鲁明,陈震等.中药联合化疗治疗晚期胰腺癌32例临床研究.中医杂志2006,47(2):115-117.
[3]沈晔华,刘鲁明,孟志强,等.清胰化积方为主综合治疗晚期胰腺癌64例生存分析.中医杂志.2009.50(1):39-42.
[4]刘鲁明,沈晔华,陈震,于尔辛,等.胰腺癌伴肝转移的中西医综合治疗临床研究.见:第二届国际中西医结合、中医肿瘤学术研讨会论文汇编(广州),2004:215-221.
[5]Liu LM.Comprehensive therapy of pancreatic cancer by integrative traditional and western medicine.Chin J Integr Meal.2004;10(3):236-237.
[6]张剑军,陈震,石卫东,等.清胰化积方对移植胰腺癌小鼠免疫抑制因子及脾淋巴细胞功能的影响.中华中医药杂志 2008;14(6):49-51.
[7]沈晔华,刘鲁明,沈瑾,等.清胰消积方对实验性胰腺癌体内生长和细胞周期的影响.中国中医基础医学杂志,2006,12(2):97-99.
[8]傅洁,刘鲁明,沈瑾等.清胰化积方联合健择对SW1990抑瘤及逆转MDR作用观察.中国中医基础医学杂志.2007,13(4):289-291.
[9]沈晔华,刘鲁明,陆燕,等.清胰消积中药对实验性胰腺癌基因表达的影响.中国癌症杂志,2005,15(5):454-457,461.
[10]Kyriazis AP,McCombs WB 3rd,Sandberg AA,et al.Establishment and characterization of human pancreatic adenocarcinoma cell line SW-1990 in tissue culture and the nude mouse.Cancer Res.1983;43(9):4393-4401.
[11]Schoumacher RA,Ram J,Iannuzzi MC,et al.A cystic fibrosis pancreatic adenocarcinoma cell line.Proc Natl Acad Sci USA.1990;87(10):4012-6.
[12]McIntosh JC,Schoumacher RA,Tiller RE.Pancreatic adenocarcinoma in a patient with cystic fibrosis.Am J Med.1988;85(4):592.
[13]Kaori FO,Etsuro O,Masatoshi S,et al.Capecitabine improves cancer cachexia and normalizes IL-6 and PTHrP levels in mouse cancer cachexia models.Cancer Chemother Pharmacol;2007,59:807-815.
[14]Itasu N,Itsuro T,Tetsuya Y,et al.Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum.Int J Cancer.2004;112(1):135-42.
[15]王鹏.胰腺癌中医证与病机及清胰化积方抑瘤作用机制探讨.In肿瘤医院.上海:复旦大学,2008.
[16]Shi WD,Meng ZQ,Chen Z,et al.Identification of liver metastasis-related genes in a novel human pancreatic carcinoma cell model by microarray analysis.Cancer Lett.2009.[Epub ahead of print]
[17]张剑军,陈震,石卫东,等.清胰化积方对移植胰腺癌小鼠免疫抑制因子及脾淋巴细胞功能的影响.中国实验方剂学杂志.2008.14(6):49-51.
[18]韩锐,孙燕.抗肿瘤药体内研究的常用方法:新世纪癌的化学预防与药物治疗.北京:人民军医出版社.2005:44-56.
[19]袁世珍,主编.胰腺癌.上海:上海科学技术出版社 2001:129.
[20]Hotz H,Reber H,Hotz B,et al.An orthotop ic nude mouse model for evaluating pathophysiology and therapy of pancreatic cancer.Pancreas,2004,26(4):eg9-e98.
[21]Fu X,Guadagni F,Hoffman RM.A metastatic nude-mouse model of human pancreatic cancer constructed orthotopically with histologically intact patient specimens.Proc Natl Acad Sci U S A.1992;89(12):5645-9.
[22]Schwarz RE,McCarty TM,Peralta EA,et al.An orthotopic in vivo model of human pancreatic cancer.Surgery.1999;126(3):562-7.
[23]Gallatin WM,Weissman IL,Butcher EC.A cell-surface molecule involved in organ-specific homing of lymphocytes.1983.J Immunol.2006;177(1):5-9.
[24]Kozlowski JM,Fidler IJ,Campbell D,et al.Metastatic behavior of human tumor cell lines grown in the nude mouse.Cancer Rresearch,1984,44(8):3522-9.
[25]Coltrini D,Gualandris A,Nelli EE,et al.Growth advantage and vascularization induced by basic fibroblast growth factor overexpression in endometrial HEC-1-B cells:an export-dependent mechanism of action.Cancer Research,1995;55(20):4729-38.
[26]Giavazzi R,Campbell DE,Jessup JM,et al.Metastatic behavior of tumor cells isolated from primary and metastatic human colorectal carcinomas implanted into different sites in nude mice.CancerResearch,1986,46(4 Pt 2):1928-33.
[27]Sordath C,Ueyama Y,Fogh J.Metastasis of tumor xenografts in the nude mouse.In:Fogh J,Giovanella BC.The nude mouse in experimental and clinical research.New York:Academic Press,1982:95-143.
[28]Fidler IJ.Critical factors in the biology of human cancer metastasis.Am Surg,1995,61:1065-1066.
[29]余泽前,周家华,胡亮,等.人胰腺癌细胞CFPAC-1裸小鼠原位移植瘤模型的建立.东南大学学报(医学版).2008,27(1):27-30.
[30]曾益新.肿瘤学.第1版.北京:人民卫生出版社,1999:80.
[31]成细华,田道法.中医药调节肿瘤细胞信号传导的研究进展.中国中医药信息杂志.2006,13(3):106-108.
[32]Augustin HG.Antiangiogenic tumour therapy:will it work?.Trends Pharmacol Sci,1995;19:216.
[33]李春海,李克勤.肿瘤微血管生成的机制与肿瘤侵袭和转移.中华肿瘤杂志,2000,22(3):181-183.
[34]Seo Y,Baba H,Fukuda T,et al.High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma.Cancer.2000;88:2239-2245.
[35]Niedergethmann M,Hildenbrand R,Wostbrock B,et al.High expression of vascular endothelial growth factor predicts early recurrence and poor prognosis after curative resection for ductal adenocarcinoma of the pancreas.Pancreas.2002;25:122-129.
[36]Tawada K,Ishihara T,Kobayashi A,et al.Quantitative analysis of vascular endothelial growth factor in liver metastases from pancreatic carcinoma as a predictor of chemotherapeutic effect and prognosis.Clin Cancer Res.2008;14(22):7438-43.
[37]YamamotoY,Toi M,Kondo S,et al.Concentrations of vascular endothelial growth factor in the sera of normale ontrols and cancer patients.Clin Cancer Res 1996;2:821-6.
[38]Pooh RT,Lau CP,Cheung ST,et al.Quantitative correlation of serum levels and tumor expression of vascular endothelial growth factor in patients with hepatocellular carcinoma.Cancer Res 2003;63:3121-6.
[39]Karayiannakis AJ,Bolanaki H,Syrigos KN,et al.Serum vascular endothelial growth factor levels in pancreatic cancer patients correlate with advanced and metastatic disease and poor prognosis.Cancer Lett.2003;194(1):119-24.
[40]Chang YT,Chang MC,Wei SC,et al.Serum vascular endothelial growth factor/soluble vascular endothelial growth factor receptor 1 ratio is an independent prognostic marker in pancreatic cancer.Pancreas.2008;37(2):145-50.
[41]Balsari A,MaierJA,Colnaghi MI,et al.Correlation between tumor vascularity,vascular endothelial growth factor production by tumor cells,serum vascular endothelial growth factor levels,and serum angiogenic activity in patients with breast carcinoma.Lab Invest 1999;79:897-902.
[42]Ohta M,Konno H,Tanaka T,et al.The significance of circulating vascular endothelial growth factor(VEGF) protein in gastric cancer.Cancer Lett 2003;192:215-25.
[43]Rueda A,Olmos D,Villareal V,et al.Elevated vascular endothelial growth factor pretreatment levels are correlated with the tumor burden in Hodgkin lymphoma and continue to be elevated in prolonged complete remission.Clin Lymphoma Myeloma 2007;7:400-5.
[44]Webb NJ,Bottomley MJ,Watson CJ,et al.Vascular endothelial growth factor(VEGF) is released from platelets during blood clotting:implications for measurement of circulating VEGF levels in clinical disease.Clin Sci(Lond) 1998;94:395-404.
[45]Kahn-Perles B,Boyer C,Arnold B,et al.Acquisition of HLA class Ⅰ W6/32 defined antigenic determinant by heavy chains from different species following association with bovine beta 2-microglobulin.J Immunol.1987;138:2190-2196.
[46]Ferrier P,Layet C,Calllol DH,et al.The association between murine beta 2-microglobulin and HLA class Ⅰ heavy chains results in serologically detectable conformational changes of both chains.J Immunol.1985;135:1281-1287.
[47]Tsimberidou AM,Estey E,Wen S,et al.The prognostic significance of cytokine levels in newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndromes.Cancer.2008;113(7):1605-13.
[48]Ebrahimi B,Tucker SL,Li D,et al.Cytokines in pancreatic carcinoma:correlation with phenotypic characteristics and prognosis.Cancer.2004;101(12):2727-36.
[49]Koch AE,MM Hailoran,CJ Haskell,et al.Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1.Nature.1995;376:517-519.
[50]Alexiou D,Karayiannakis AJ,Syrigos KN,et al.Clinical significance of serum levels of E-selectin,intercellular adhesionmolecule-1,and vascular cell adhesion molecule-1 in gastric cancer patients.Am J Gastroenterol.2003,98,478-485.
[51]Velikova G,Banks RE,Gearing A,et al.Serum concentrations of soluble adhesion molecules in patients with colorectal cancer.Br J Cancer 1998,77,1857-1863.
[52]Alexiou D,Karayiannakis AJ,Syrigos KN,et al.Serum levels of E-selectin,ICAM-1 and VCAM-1 in colorectal cancer patients:correlations with clinicopathological features,patients survival and tumor surgery.Eur J Cancer 2001,37,2392-2397.
[53]O'Hanlon DM,Fitzsimons H,Lynch J,et al.Soluble adhesion molecules(E-selectin,ICAM-1and VCAM-1) in breast carcinoma.Eur J Cancer 2002,38,2252-2257.
[54]Franzke A,Probst-Kepper M,Buer J,et al.Elevated pretreatment serum levels of soluble vascular cell adhesion molecule 1 and lactate dehydrogenase as predictors of survival in cutaneous metastatic malignant melanoma.Br J Cancer 1998,78,40-45.
[55]Christiansen I,Sundstro¨m C,To¨tterman TH.Elevated serum levels of soluble vascular cell adhesion molecule-1(sVCAM-1) closely reflect tumour burden in chronic B-lymphocytic leukaemia.Br J Haematol 1998,I03,1129-1137.
[56]Kamezaki S,Kurozawa Y,Iwai N,et al.Serum levels of soluble ICAM-1 and VCAM-1 predict pre-clinical cancer.Eur J Cancer.2005;41(15):2355-9.
[57]Heldin CH,Miyazono K,ten Dijke P.TGF-beta signalling from cell membrane to nucleus through SMAD proteins.Nature.1997;390(6659):465-71.
[58]Perlman R,Schiemann WP,Brooks MW,et al.TGF-beta-induced apoptosis is mediated by the adapter protein Daxx that facilitates JNK activation.Nat Cell Biol.2001;3(8):708-14.
[59]Lin Y,Kikuchi S,Tamakoshi A,et al.Serum transforming growth factor-betal levels and pancreatic cancer risk:a nested case-control study(Japan).Cancer Causes Control.2006;17(8):1077-82.
[60]Ottaviano AJ,Sun L,Ananthanarayanan V,et al.Extracellular matrix-mediated membrane-type 1matrix metalloproteinase expression in pancreatic ductal cells is regulated by transforming growth factor-betal.Cancer Res.2006;66(14):7032-40.
[61]Kishimoto T,Akira S,Narazaki M,et al.Interleukin-6 family of cytokines and gp130.Blood.1995;86:1243-1254.
[62]Freeman GJ,Freedman AS,Rabinowe SN,et al.Interleukin 6 gene expression in normal and neoplastic B cells.J Clin Invest.1989;83:1512-1518.
[63]Seymour JF,Kurzrock R.Interleukin-6:biologic properties and role in lymphoproliferative disorders.In:Freireieh EJ,Kantarjian HM,editors.Molecular genetics and therapy of leukeraia.Boston:Kluwer Academic Publishers,1996:204-217.
[64]Klein B,Zhang XG,Lu ZY,et al.Interleukin-6 in human multiple myeloma.Blood.1995;85:863-872.
[65]Seymour JF,Talpaz M,Cabanillas F,et al.Serum interleukin-6 levels correlate with prognosis in diffuse large-cell lymphoma.J Clin Oncol.1995;13:575-582.
[66]Blay JY,Negrier S,Combaret V,et al.Serum level of interleukin 6 as a prognosis factor in metastatic renal carcinoma.Cancer Res.1992;50:3317-3322.
[67]Twillie DA,Eisenberger MA,Carducce MA,et al.Interleukin-6:a candidate mediator of human prostate cancer morbidity.Urology.1995;45:542-549.
[68]Berek JS,Chung C,Kaidi K,et al.Serum interleukin-6 levels correlate with disease status in patients with epithelial ovarian cancer.Am J Obstet Gynecol.1991;164:1038-1043.
[69]Ludwig H,Nachbaur DM,Fritz E,et al.Interleukin-6 is a prognostic factor in multiple myeloma.Blood.1991;77:2794-2795.
[70]Chung YC,Chang YF.Serum interleukin-6 levels reflect the disease status of colorectal cancer.J Surg Oncol.2003;83:222-226.
[71]Talar-Wojnarowska R,Gasiorowska A,Smolarz B,et al.Clinical significance of interleukin-6(IL-6) gene polymorphism and IL-6 serum level in pancreatic adenocarcinoma and chronic pancreatitis.Dig Dis Sci.2009;54(3):683-9.
[72]Baggiolini M,Walz A,Kunkel SL.Neutrophil-activating peptide-1/interleukin-8,a novel cytokine that activates neutrophils.J.Clin.Invest.1989.84:1045-1049.
[73]Xie K.Survey:interleukin-8 and human cancer biology.Cytokine Growth Factor Rev.2001;12:375-391.
[74]Bellone G,Smirne C,Mauri FA,et al.Cytokine expression profile in human pancreatic carcinoma cells and in surgical specimens:implications for survival.Cancer Immunol Immunother.2006;55(6):684-98.
[75]Jacks T,Weinberg RA.Cell-cycle control and its watchman.Nature.1996;381:643-644.
[76]Morgan DO.Prociples of CDK regulation.Nature.1995;374:131-134.
[77]Nasmyth K.Viewpoint:putting the cell cycle in order.Science.1996;274:1643-1645.
[78]Jacks T,Weinberg RA.The expanding role of cell cycle regulators.Science.1998;280:1035-1036.
[79]Melo J,Toczyski D.A unified view of the DNA-damage checkpoint.Curr Opin Cell Biol.2002,14(2):237-245.
[80]Malty A,Mckenna WG,Muschel RJ.The molecular basis for cell cycle delays following ionizing radiation:a review.Radiother Oncol.1994,31(1):1-13.
[78]Sang QXA.Complex role of matrix metalloproteinases in angiogenesis.Cell Res,1998,8(2):171-177.
[79]Yang X,Staten ED,Howard JM,et al.Invasiveness and MMP expression in pancreatic carcinoma.J Surg Res.2001;98(1):33-9.
[80]Jimenez RE,Hartwig W,Antoniu BA,et al.Effect of matrix metalloproteinase inhibition on pancreatic cancer invasion and metastasis:an additive strategy for cancer control.Ann Surg.2000;231(5):644-54.
[81]Hirai H,Maru Y,Hagiwara K,et al.A novel putative tyrosine kinase receptor encoded by the eph gene.Science,1987;238(4834):1717-1720.
[82]Wu Q,Suo Z,Kristensen GB,et al.The prognostic impact of EphB2/B4 expression on patients with advanced ovarian carcinoma.Gynecol Oncol.2006;102(1):15-21.
[83]Wu Q,Suo Z,Risberg B,et al.Expression of Ephb2 and Ephb4 in breast carcinoma.Pathol Oncol Res.2004;10(1):26-33.
[84]Nakada M,Niska JA,Tran NL,et al.EphB2/R-Ras signaling regulates glioma cell adhesion,growth,and invasion.Am J Pathol.2005;167(2):565-76.
[85]Nakada M,Niska JA,Miyamori H,et al.The phosphorylation of EphB2 receptor regulates migration and invasion of human glioma cells.Cancer Res.2004;64(9):3179-85.
[86]Huusko P,Ponciano-Jackson D,Wolf M,et al.Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer.Nat Genct.2004;36(9):979-83.
[87]Lugli A,Spichtin H,Maurer R,et al.EphB2 expression across 138 human tumor types in a tissue microarray:high levels of expression in gastrointestinal cancers.Clin Cancer Res.2005;11(18):6450-8.
1.Miyamori H,Takino T,Kobayashi Y,et al.Claudin promotes activation of pro-matrix metalloproteinase-2 mediated by membrane-type matrix metalloproteinases.J Biol Chem.2001;276:28204-11.
2.Nakada M,Niska JA,Miyamori H,et al.The phosphorylation of EphB2 receptor regulates migration and invasion of human glioma cells.Cancer Res.2004;64(9):3179-85.
3.Pebernard S,Iggo RD.Determinants of interferon-stimulated gene induction by RNAi vectors.Differentiation.2004;72(2-3):103-11.
[1]Zhang B.Wang ZF.Tang MZ,et al.Growth inhibition and apoptosis-induced effect on human cancer cells of toosendanin,a triterpenoid derivative from chinese traditional medicine.Investigational New Drugs.2005,23(6):547-553.
[2]Jiang J.Slivova V.Harvey K,et al.Ganoderma lucidum suppresses growth of breast cancer cells through the inhibition of Akt/NF-kappaB signaling.Nutrition & Cancer,2004,49(2):209-216.
[3]郑丽端,童强松,吴翠环,等.姜黄素诱导卵巢癌细胞株A2780细胞周期阻滞和凋亡.华中科技大学学报(医学版).2003,32(2):209-214.
[4]单保恩,付小梅,华正祥,等.中药五加皮提取成分抗肿瘤活性作用机理研究.中国中西医结合 杂志,2005,25(9):825-828.
[5]李学松,梁云燕,王代树,等.复方中药紫龙金对前列腺癌细胞系LNCaP的体外作用.中国中西医结合杂志,2004,24(7):621-624.
[6]张大鹏,孔棣.回生口服液对人结肠癌THC8908细胞抑制作用.华西医学,2005,20(2):338-339.
[7]熊鹰,孔小云,陈如山,等.复方犀黄丸含药血清对人肝癌细胞生长及其周期影响的实验研究.中国中医药科技.2001,8(4):217-218.
[8]Cheng YL.Chang WL.Lee SC,et al.Acetone extract of Angelica sinensis inhibits proliferation of human cancer cells via inducing cell cycle arrest and apoptosis.Life Sciences,2004,75(13):1579-1594.
[9]Hsu YL.Kuo PL.Lin CC.The proliferative inhibition and apoptotic mechanism of Saikosaponin D in human non-small cell lung cancer A549 cells.Life Sciences,2004,75(10):1231-1242.
[10]Kuo YC.Lin YL.Huang CP,et al.A tumor cell growth inhibitor from Saposhnikovae divaricata.Cancer Investigation,2002,20(7-8):955-64.
[11]曾小莉,涂植光.端粒酶在人参皂甙Rh2诱导肝癌细胞分化中的作用.癌症,2004,23(12):1655-1659.
[12]邓惠,罗焕敏,黄丰,等.苦参碱对C6胶质瘤细胞的增殖和原癌基因表达的影响.中药材,2004,27(6):416-419.
[13]Hsieh TC.Kunicki J.Darzynkiewicz Z,et al.Effects of extracts of Coriolus versicolor (I'm-Yunity) on cell-cycle progression and expression of interleukins-1 beta,-6,and-8 in promyelocytic HL-60 leukemic cells and mitogenically stimulated and nonstimulated human lymphocytes.Journal of Alternative & Complementary Medicine,2002,8(5):591-602.
[14]Hsieh TC.Wu JM.Differential control of growth,cell cycle progression,and gene expression in human estrogen receptor positive MCF-7 breast cancer cells by extracts derived from polysaccharopeptide I'm-Yunity and Danshen and their combination.International Journal of Oncology,2006,29(5):1215-1222.
[15]Moon SK.Jin HS.Ko CN,et al.Inhibition of human endothelial cell proliferation by Gami—Jeonggi—San(Jiawei—Zhenqi—San) is accompanied by transcriptional up-regulation of p53 and Waf1 tumor suppressor genes.Journal of Ethnopharmacology.2005,100(1-2):187-92.
[16]Li KS.Gu XF.Li P,et al.Effect of pseudolaric acid B on gastric cancer cells:inhibition of proliferation and induction of apoptosis.World Journal of Gastroenterology,2005,11(48):7555-7559.
[17]Hsieh TC.Wijeratne EK.Liang JY,et al.Differential control of growth,cell cycle progression,and expression of NF-kappaB in human breast cancer cells MCF-7,MCF-10A,and MDA-MB-231 by ponicidin and oridonin diterpenoids from the chinese herb Rabdosia rubescens.Biochemical & Biophysical Research Communications,2005,337(1):224-231.
[18]Lu QY.Jin YS.Zhang Q,et al.Ganoderma lucidum extracts inhibit growth and induce actin polymerization in bladder cancer cells in vitro.Cancer Letters,2004,216(1):9-20.
[19]Campbell MJ.Hamilton B.Shoemaker M,et al.Antiproliferative activity of Chinese medicinal herbs on breast cancer cells in vitro.Anticancer Research,2002,22(6C):3843-3852.
[20]Chang WH.Chen CH.Lu FJ.Different effects of baicalein,baicalin and wogonin on mitochondrial function,gintathione content and cell cycle progression in human hepatoma cell lines.Planta Medica,2002,68(2):128-132.
[21]杨萍,于廷曦,黄来珍,等.土贝母皂苷诱导人宫颈癌HeLa细胞周期阻滞和细胞凋亡.癌症,2002,21(4):346-350.
[22]张艰,戚好文,吴昌归,等.姜黄素对A549人肺腺癌细胞增殖抑制作用及其机制的研究.中药材,2004,27(12):923-927.
[23]鲍英,夏璐,袁耀宗,等.康莱特对Patu28988细胞周期及其调节基因表达的影响.胰腺病学,2004,4(2):82-85.
[24]徐力,王明艳,许冬青,等.三物白散加味方影响肿瘤细胞周期实验研究.陕西乒医,2005,26(11):1246-1248.
[25]Yao R.Han Z.Wang M,et al.Extract from Arca granosa L inhibits proliferation of human tumout cell lines with kidney and lung origin.Journal of International Medical Research,2006,34(4):355-361.
[26]李宝元,梁云燕,王代树.中药白龙片与HMBA对人胃癌不同周期细胞癌基因与抑癌基因表达调控的共性研究.中国中西医结合杂志,2001,21(4):286-289.
[1]Hirai H,Maru Y,Hagiwara K,et al.A novel putative tyrosine kinase receptor encoded by the eph gene.Science,1987;238(4834):1717-1720.
[2]Kiyokawa E,Takai S.Overexpression of ERK,an Eph family receptor protein tyrosine kinase,in various human tumors.Cancer Research,1994:54(14):3645-3650.
[3]Mellott DO,Burke RD.The molecular phylogeny of eph receptors and ephrin ligands.BMC Cell Biol.2008;9:27.
[4]Lugli A,Spichtin H,Maurer R,et al.EphB2 expression across 138 human tumor types in a tissue microarray:high levels of expression in gastrointestinal cancers.Clin Cancer Res.2005;11(18):6450-8.
[5]Guo DL,Zhang J,Yuen ST,et al.Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumours.Carcinogenesis.2006 Mar;27(3):454-64.
[6]Oba SM,Wang YJ,Song JP,et al.Genomic structure and loss of heterozygosity of EPHB2 in colorectal cancer.Cancer Lett.2001;164(1):97-104.
[7]Kokko A,Laiho P,Lehtonen R,et al.EPHB2 germline variants in patients with colorectal cancer or hyperplastic polyposis.BMC Cancer.2006;6:145.
[8]Liu W,Abroad SA,Jung YD,et al.Coexpression of ephrin-Bs and their receptors in colon carcinoma.Cancer.2002;94(4):934-9.
[9]Clevers H,Batlle E.EphB/EphrinB receptors and Wnt signaling in colorectal cancer.Cancer Res.2006;66:2-5.
[10]Jubb AM,Zhong F,Bheddah S,et al.EphB2 is a prognostic factor in colorectal cancer.Clin Cancer Res.2005 Jul 15;11(14):5181-7.
[11]Oshima T,Akaike M,Yoshihara K,et al.Overexpression of EphA4 gene and reduced expression of EphB2 gene correlates with liver metastasis in colorectal cancer.Int J Oncol.2008;33(3):573-7.
[12]Wu Q,Suo Z,Kristensen GB,et al.The prognostic impact of EphB2/B4 expression on patients with advanced ovarian carcinoma.Gynccol Oncol.2006;102(1):15-21.
[13]Wu Q,Suo Z,Risberg B,et al.Expression of Ephb2 and Ephb4 in breast carcinoma.Pathol Oncol Res.2004;10(1):26-33.
[14]Nakada M,Niska JA,Tran NL,et al.EphB2/R-Ras signaling regulates glioma cell adhesion, growth,and invasion.Am J Pathol.2005;167(2):565-76.
[15]Nakada M,Niska JA,Miyamori H,et al.The phosphorylation of EphB2 receptor regulates migration and invasion of human glioma cells.Cancer Res.2004;64(9):3179-85.
[16]Huusko P,Ponciano-Jackson D,Wolf M,et al.Nonsense-mediated decay mieroarray analysis identifies mutations of EPHB2 in human prostate cancer.Nat Genet.2004;36(9):979-83.
[17]Tang XX,Brodeur GM,Campling BG,et al.Coexpression of transcripts encoding EPHB receptor protein tyrosine kinases and their ephrin-B ligands in human small cell lung carcinoma.Clin Cancer Res.1999;5(2):455-60.
[18]Hafner C,Schmitz G,Meyer S,et al.Differential gene expression of Eph receptors and ephrins in benign human tissues and cancers.Clin Chem.2004;50(3):490-9.
[19]Kataoka H,Tanaka M,Kanamori M,et al.Expression profile of EFNB1,EFNB2,two ligands of EPHB2 in human gastric cancer.J Cancer Res Clin Oncol.2002;125(7):343-8.
[20]Mao W,Luis E,Ross S,et al.EphB2 as a therapeutic antibody drug target for the treatment of colorectal cancer.Cancer Res.2004;64(3):781-8.
[21]Chrencik JE,Brooun A,Recht MI,et al.Three-dimensional structure of the EphB2 receptor in complex with an antagonistic peptide reveals a novel mode of inhibition.J Biol Chem.2007;282(50):36505-13.
[2]上海市疾病预防控制中心.2004年上海市市区恶性肿瘤发病率.肿瘤,2007;27(7):594.
[3]Kleeff J,Michalski C,Friess H,et al.Pancreatic cancer:from bench to 5-year survival.Pancreas.2006;33(2):111-8.
[4]Oettle H,Post S,Neuhaus P,et al.Adjuvant chemotherapy with gemcitabine vs.observation in patients undergoing curative-intent resection of pancreatic cancer:a randomized controlled trial.JAMA.2007;297:267-277.
[5]Cameron JL,Riall TS,Coleman J,et al.One thousand consecutive pancreatico- duodenectomies.Ann Surg.2006;144:10-15.
[6]Nishimura Y,Hosotani R,Shibamoto Y,et al.External and intraoperative radiotherapy for resectable and unresectable pancreatic cancer:analysis of survival rates and complications.Int J Radiat Oncol Biol Phys.1997.39:39-49.
[7]Millikan KW,Deziel DJ,Silverstein JC,et al.Prognostic factors associated with resectable adenocarcinoma of the head of the pancreas.Am Surg.1999.65:618-623;discussion 623-614.
[8]Fine RL,Fogelman DR,Schreibman SM,et al.The gemcitabine,docetaxel,and capecitabine (GTX) regimen for metastatic pancreatic cancer:a retrospective analysis.Cancer Chemother Pharmacol,2008;61(1):167-175.
[9]Okusaka T,Ishii H,Funakoshi A,et al.A phase Ⅰ/Ⅱ study of combination chemotherapy with gemcitabine and 5-fluorouracil for advanced pancreatic cancer.Jpn J Clin Oncol.2006;36(9):557-63.
[10]谢德荣,梁汉霖,杨琼等.吉西他滨联合卡培他滨一线治疗晚期胰腺癌的Meta分析.世界华人消化杂志,2007;15(16):1868-1871.
[I1]Ulrich-Pur H,Raderer M,Kornek GV,et al.Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced adenocarcinoma.Br J Cancer,2003;88:1180-1184.
[12]Reni M,Pasetto L,Aprile G,et al.Raltitrexed-eloxatin salvage chemotherapy in gemcitabine-resistant metastatic pancreatic cancer.Br J Cancer,2006;94(6):785-791.
[13]Hazard L.The role of radiation therapy in pancreas cancer.Gastrointest Cancer Res.2009;3(1):20-8.
[14]Huguet F,Girard N,Seblain-El Guerche C,et al.Chemoradiotherapy in the Management of Locally Advanced Pancreatic Carcinoma:A Qualitative Systematic Review.J Clin Oncol.2009.[Epub ahead of print]
[15]Timke C,Debus JP.The role of radiation therapy in treatment of pancreatic cancer from the viewpoint of radio-oncologists.Radiologe.2009;49(2):149-53.
[16]Dubinsky TJ,Cuevas C,Dighe MK,et al.High-intensity focused ultrasound:current potential and oncologic applications.AJR Am J Roentgenol.2008;190(1):191-9.
[17]Moore MJ,Goldstein D,Hamm J,et al.Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer:a phase Ⅲ trial of the National Cancer Institute of Canada Clinical Trials Group.J Clin Oncol.2007.25:1960-1966.
[18]Kindler HL,Friberg G,Singh DA,et al.Phase Ⅱ trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer.J Clin Oncol.2005.23:8033-8040.
[19]Xiong HQ,Rosenberg A,LoBuglio A,et al.Cetuximab,a monoclonal antibody targeting the epidermal growth factor receptor,in combination with gemcitabine for advanced pancreatic cancer:a multicenter phase Ⅱ Trial.J Clin Oncol.2004.22:2610-2616.
[20]No listed authors.Gemcitabine plus bevacizumab no better than gemcitabine alone in clinical study of 600 patients with pancreatic cancer.Cancer Biol Ther.2007;6:137.
[21]Cascinu S,Berardi R,Labianca R,et al.Cetuximab plus gemcitabine and cisplatin compared with gemcitabine and cisplatin alone in patients with advanced pancreatic cancer:a randomised,multicentre,phase Ⅱ trial,Lancet Oncol.2008;9(1):39-44.
[22]沈晔华,刘鲁明,陈震等.中药联合化疗治疗晚期胰腺癌32例临床研究.中医杂志2006,47(2):115-117.
[23]沈晔华,刘鲁明,孟志强,等.清胰化积方为主综合治疗晚期胰腺癌64例生存分析.中医杂志.2009.50(1):39-42.
[24]沈晔华,刘鲁明,沈瑾,等.清胰消积方对实验性胰腺癌体内生长和细胞周期的影响.中国中医基础医学杂志.2006.12(2):97-99.
[25]沈晔华,刘鲁明,陆燕.清胰消积中药对实验性胰腺癌基因表达的影响.中国癌症杂志.2005.15(5):454-461.
[26]傅洁,刘鲁明,沈瑾,等.清胰化积方联合健择对SW1990抑瘤及逆转MDR作用观察.中国中医基础医学杂志.2007.13(4):289-291.
[27]陈培丰,刘鲁明.清胰消积方抑瘤效应及诱导肿瘤细胞凋亡作用的研究.中国中医药科技.2000,7(3):145-146.
[28]陈培丰,刘鲁明.清胰消积方抑制肝癌腹水和肺转移作用的实验研究.浙江中西医结合杂志,2000,10(6):340-341.
[29]Schoumacher RA,Ram J,Iannuzzi MC,et al.A cystic fibrosis pancreatic adenocarcinoma cell line.Proc Natl Acad Sci USA.1990;87(10):4012-6.
[30]余泽前,周家华,胡亮,等.人胰腺癌细胞CFPAC-1裸小鼠原位移植瘤模型的建立.东南大学学报(医学版).2008,27(1):27-30.
[1]刘鲁明.胰腺癌的中医病因病机与辨病论治.中西医结合学报.2008,6(12):1297-1299.
[2]沈晔华,刘鲁明,陈震等.中药联合化疗治疗晚期胰腺癌32例临床研究.中医杂志2006,47(2):115-117.
[3]沈晔华,刘鲁明,孟志强,等.清胰化积方为主综合治疗晚期胰腺癌64例生存分析.中医杂志.2009.50(1):39-42.
[4]刘鲁明,沈晔华,陈震,于尔辛,等.胰腺癌伴肝转移的中西医综合治疗临床研究.见:第二届国际中西医结合、中医肿瘤学术研讨会论文汇编(广州),2004:215-221.
[5]Liu LM.Comprehensive therapy of pancreatic cancer by integrative traditional and western medicine.Chin J Integr Meal.2004;10(3):236-237.
[6]张剑军,陈震,石卫东,等.清胰化积方对移植胰腺癌小鼠免疫抑制因子及脾淋巴细胞功能的影响.中华中医药杂志 2008;14(6):49-51.
[7]沈晔华,刘鲁明,沈瑾,等.清胰消积方对实验性胰腺癌体内生长和细胞周期的影响.中国中医基础医学杂志,2006,12(2):97-99.
[8]傅洁,刘鲁明,沈瑾等.清胰化积方联合健择对SW1990抑瘤及逆转MDR作用观察.中国中医基础医学杂志.2007,13(4):289-291.
[9]沈晔华,刘鲁明,陆燕,等.清胰消积中药对实验性胰腺癌基因表达的影响.中国癌症杂志,2005,15(5):454-457,461.
[10]Kyriazis AP,McCombs WB 3rd,Sandberg AA,et al.Establishment and characterization of human pancreatic adenocarcinoma cell line SW-1990 in tissue culture and the nude mouse.Cancer Res.1983;43(9):4393-4401.
[11]Schoumacher RA,Ram J,Iannuzzi MC,et al.A cystic fibrosis pancreatic adenocarcinoma cell line.Proc Natl Acad Sci USA.1990;87(10):4012-6.
[12]McIntosh JC,Schoumacher RA,Tiller RE.Pancreatic adenocarcinoma in a patient with cystic fibrosis.Am J Med.1988;85(4):592.
[13]Kaori FO,Etsuro O,Masatoshi S,et al.Capecitabine improves cancer cachexia and normalizes IL-6 and PTHrP levels in mouse cancer cachexia models.Cancer Chemother Pharmacol;2007,59:807-815.
[14]Itasu N,Itsuro T,Tetsuya Y,et al.Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum.Int J Cancer.2004;112(1):135-42.
[15]王鹏.胰腺癌中医证与病机及清胰化积方抑瘤作用机制探讨.In肿瘤医院.上海:复旦大学,2008.
[16]Shi WD,Meng ZQ,Chen Z,et al.Identification of liver metastasis-related genes in a novel human pancreatic carcinoma cell model by microarray analysis.Cancer Lett.2009.[Epub ahead of print]
[17]张剑军,陈震,石卫东,等.清胰化积方对移植胰腺癌小鼠免疫抑制因子及脾淋巴细胞功能的影响.中国实验方剂学杂志.2008.14(6):49-51.
[18]韩锐,孙燕.抗肿瘤药体内研究的常用方法:新世纪癌的化学预防与药物治疗.北京:人民军医出版社.2005:44-56.
[19]袁世珍,主编.胰腺癌.上海:上海科学技术出版社 2001:129.
[20]Hotz H,Reber H,Hotz B,et al.An orthotop ic nude mouse model for evaluating pathophysiology and therapy of pancreatic cancer.Pancreas,2004,26(4):eg9-e98.
[21]Fu X,Guadagni F,Hoffman RM.A metastatic nude-mouse model of human pancreatic cancer constructed orthotopically with histologically intact patient specimens.Proc Natl Acad Sci U S A.1992;89(12):5645-9.
[22]Schwarz RE,McCarty TM,Peralta EA,et al.An orthotopic in vivo model of human pancreatic cancer.Surgery.1999;126(3):562-7.
[23]Gallatin WM,Weissman IL,Butcher EC.A cell-surface molecule involved in organ-specific homing of lymphocytes.1983.J Immunol.2006;177(1):5-9.
[24]Kozlowski JM,Fidler IJ,Campbell D,et al.Metastatic behavior of human tumor cell lines grown in the nude mouse.Cancer Rresearch,1984,44(8):3522-9.
[25]Coltrini D,Gualandris A,Nelli EE,et al.Growth advantage and vascularization induced by basic fibroblast growth factor overexpression in endometrial HEC-1-B cells:an export-dependent mechanism of action.Cancer Research,1995;55(20):4729-38.
[26]Giavazzi R,Campbell DE,Jessup JM,et al.Metastatic behavior of tumor cells isolated from primary and metastatic human colorectal carcinomas implanted into different sites in nude mice.CancerResearch,1986,46(4 Pt 2):1928-33.
[27]Sordath C,Ueyama Y,Fogh J.Metastasis of tumor xenografts in the nude mouse.In:Fogh J,Giovanella BC.The nude mouse in experimental and clinical research.New York:Academic Press,1982:95-143.
[28]Fidler IJ.Critical factors in the biology of human cancer metastasis.Am Surg,1995,61:1065-1066.
[29]余泽前,周家华,胡亮,等.人胰腺癌细胞CFPAC-1裸小鼠原位移植瘤模型的建立.东南大学学报(医学版).2008,27(1):27-30.
[30]曾益新.肿瘤学.第1版.北京:人民卫生出版社,1999:80.
[31]成细华,田道法.中医药调节肿瘤细胞信号传导的研究进展.中国中医药信息杂志.2006,13(3):106-108.
[32]Augustin HG.Antiangiogenic tumour therapy:will it work?.Trends Pharmacol Sci,1995;19:216.
[33]李春海,李克勤.肿瘤微血管生成的机制与肿瘤侵袭和转移.中华肿瘤杂志,2000,22(3):181-183.
[34]Seo Y,Baba H,Fukuda T,et al.High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma.Cancer.2000;88:2239-2245.
[35]Niedergethmann M,Hildenbrand R,Wostbrock B,et al.High expression of vascular endothelial growth factor predicts early recurrence and poor prognosis after curative resection for ductal adenocarcinoma of the pancreas.Pancreas.2002;25:122-129.
[36]Tawada K,Ishihara T,Kobayashi A,et al.Quantitative analysis of vascular endothelial growth factor in liver metastases from pancreatic carcinoma as a predictor of chemotherapeutic effect and prognosis.Clin Cancer Res.2008;14(22):7438-43.
[37]YamamotoY,Toi M,Kondo S,et al.Concentrations of vascular endothelial growth factor in the sera of normale ontrols and cancer patients.Clin Cancer Res 1996;2:821-6.
[38]Pooh RT,Lau CP,Cheung ST,et al.Quantitative correlation of serum levels and tumor expression of vascular endothelial growth factor in patients with hepatocellular carcinoma.Cancer Res 2003;63:3121-6.
[39]Karayiannakis AJ,Bolanaki H,Syrigos KN,et al.Serum vascular endothelial growth factor levels in pancreatic cancer patients correlate with advanced and metastatic disease and poor prognosis.Cancer Lett.2003;194(1):119-24.
[40]Chang YT,Chang MC,Wei SC,et al.Serum vascular endothelial growth factor/soluble vascular endothelial growth factor receptor 1 ratio is an independent prognostic marker in pancreatic cancer.Pancreas.2008;37(2):145-50.
[41]Balsari A,MaierJA,Colnaghi MI,et al.Correlation between tumor vascularity,vascular endothelial growth factor production by tumor cells,serum vascular endothelial growth factor levels,and serum angiogenic activity in patients with breast carcinoma.Lab Invest 1999;79:897-902.
[42]Ohta M,Konno H,Tanaka T,et al.The significance of circulating vascular endothelial growth factor(VEGF) protein in gastric cancer.Cancer Lett 2003;192:215-25.
[43]Rueda A,Olmos D,Villareal V,et al.Elevated vascular endothelial growth factor pretreatment levels are correlated with the tumor burden in Hodgkin lymphoma and continue to be elevated in prolonged complete remission.Clin Lymphoma Myeloma 2007;7:400-5.
[44]Webb NJ,Bottomley MJ,Watson CJ,et al.Vascular endothelial growth factor(VEGF) is released from platelets during blood clotting:implications for measurement of circulating VEGF levels in clinical disease.Clin Sci(Lond) 1998;94:395-404.
[45]Kahn-Perles B,Boyer C,Arnold B,et al.Acquisition of HLA class Ⅰ W6/32 defined antigenic determinant by heavy chains from different species following association with bovine beta 2-microglobulin.J Immunol.1987;138:2190-2196.
[46]Ferrier P,Layet C,Calllol DH,et al.The association between murine beta 2-microglobulin and HLA class Ⅰ heavy chains results in serologically detectable conformational changes of both chains.J Immunol.1985;135:1281-1287.
[47]Tsimberidou AM,Estey E,Wen S,et al.The prognostic significance of cytokine levels in newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndromes.Cancer.2008;113(7):1605-13.
[48]Ebrahimi B,Tucker SL,Li D,et al.Cytokines in pancreatic carcinoma:correlation with phenotypic characteristics and prognosis.Cancer.2004;101(12):2727-36.
[49]Koch AE,MM Hailoran,CJ Haskell,et al.Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1.Nature.1995;376:517-519.
[50]Alexiou D,Karayiannakis AJ,Syrigos KN,et al.Clinical significance of serum levels of E-selectin,intercellular adhesionmolecule-1,and vascular cell adhesion molecule-1 in gastric cancer patients.Am J Gastroenterol.2003,98,478-485.
[51]Velikova G,Banks RE,Gearing A,et al.Serum concentrations of soluble adhesion molecules in patients with colorectal cancer.Br J Cancer 1998,77,1857-1863.
[52]Alexiou D,Karayiannakis AJ,Syrigos KN,et al.Serum levels of E-selectin,ICAM-1 and VCAM-1 in colorectal cancer patients:correlations with clinicopathological features,patients survival and tumor surgery.Eur J Cancer 2001,37,2392-2397.
[53]O'Hanlon DM,Fitzsimons H,Lynch J,et al.Soluble adhesion molecules(E-selectin,ICAM-1and VCAM-1) in breast carcinoma.Eur J Cancer 2002,38,2252-2257.
[54]Franzke A,Probst-Kepper M,Buer J,et al.Elevated pretreatment serum levels of soluble vascular cell adhesion molecule 1 and lactate dehydrogenase as predictors of survival in cutaneous metastatic malignant melanoma.Br J Cancer 1998,78,40-45.
[55]Christiansen I,Sundstro¨m C,To¨tterman TH.Elevated serum levels of soluble vascular cell adhesion molecule-1(sVCAM-1) closely reflect tumour burden in chronic B-lymphocytic leukaemia.Br J Haematol 1998,I03,1129-1137.
[56]Kamezaki S,Kurozawa Y,Iwai N,et al.Serum levels of soluble ICAM-1 and VCAM-1 predict pre-clinical cancer.Eur J Cancer.2005;41(15):2355-9.
[57]Heldin CH,Miyazono K,ten Dijke P.TGF-beta signalling from cell membrane to nucleus through SMAD proteins.Nature.1997;390(6659):465-71.
[58]Perlman R,Schiemann WP,Brooks MW,et al.TGF-beta-induced apoptosis is mediated by the adapter protein Daxx that facilitates JNK activation.Nat Cell Biol.2001;3(8):708-14.
[59]Lin Y,Kikuchi S,Tamakoshi A,et al.Serum transforming growth factor-betal levels and pancreatic cancer risk:a nested case-control study(Japan).Cancer Causes Control.2006;17(8):1077-82.
[60]Ottaviano AJ,Sun L,Ananthanarayanan V,et al.Extracellular matrix-mediated membrane-type 1matrix metalloproteinase expression in pancreatic ductal cells is regulated by transforming growth factor-betal.Cancer Res.2006;66(14):7032-40.
[61]Kishimoto T,Akira S,Narazaki M,et al.Interleukin-6 family of cytokines and gp130.Blood.1995;86:1243-1254.
[62]Freeman GJ,Freedman AS,Rabinowe SN,et al.Interleukin 6 gene expression in normal and neoplastic B cells.J Clin Invest.1989;83:1512-1518.
[63]Seymour JF,Kurzrock R.Interleukin-6:biologic properties and role in lymphoproliferative disorders.In:Freireieh EJ,Kantarjian HM,editors.Molecular genetics and therapy of leukeraia.Boston:Kluwer Academic Publishers,1996:204-217.
[64]Klein B,Zhang XG,Lu ZY,et al.Interleukin-6 in human multiple myeloma.Blood.1995;85:863-872.
[65]Seymour JF,Talpaz M,Cabanillas F,et al.Serum interleukin-6 levels correlate with prognosis in diffuse large-cell lymphoma.J Clin Oncol.1995;13:575-582.
[66]Blay JY,Negrier S,Combaret V,et al.Serum level of interleukin 6 as a prognosis factor in metastatic renal carcinoma.Cancer Res.1992;50:3317-3322.
[67]Twillie DA,Eisenberger MA,Carducce MA,et al.Interleukin-6:a candidate mediator of human prostate cancer morbidity.Urology.1995;45:542-549.
[68]Berek JS,Chung C,Kaidi K,et al.Serum interleukin-6 levels correlate with disease status in patients with epithelial ovarian cancer.Am J Obstet Gynecol.1991;164:1038-1043.
[69]Ludwig H,Nachbaur DM,Fritz E,et al.Interleukin-6 is a prognostic factor in multiple myeloma.Blood.1991;77:2794-2795.
[70]Chung YC,Chang YF.Serum interleukin-6 levels reflect the disease status of colorectal cancer.J Surg Oncol.2003;83:222-226.
[71]Talar-Wojnarowska R,Gasiorowska A,Smolarz B,et al.Clinical significance of interleukin-6(IL-6) gene polymorphism and IL-6 serum level in pancreatic adenocarcinoma and chronic pancreatitis.Dig Dis Sci.2009;54(3):683-9.
[72]Baggiolini M,Walz A,Kunkel SL.Neutrophil-activating peptide-1/interleukin-8,a novel cytokine that activates neutrophils.J.Clin.Invest.1989.84:1045-1049.
[73]Xie K.Survey:interleukin-8 and human cancer biology.Cytokine Growth Factor Rev.2001;12:375-391.
[74]Bellone G,Smirne C,Mauri FA,et al.Cytokine expression profile in human pancreatic carcinoma cells and in surgical specimens:implications for survival.Cancer Immunol Immunother.2006;55(6):684-98.
[75]Jacks T,Weinberg RA.Cell-cycle control and its watchman.Nature.1996;381:643-644.
[76]Morgan DO.Prociples of CDK regulation.Nature.1995;374:131-134.
[77]Nasmyth K.Viewpoint:putting the cell cycle in order.Science.1996;274:1643-1645.
[78]Jacks T,Weinberg RA.The expanding role of cell cycle regulators.Science.1998;280:1035-1036.
[79]Melo J,Toczyski D.A unified view of the DNA-damage checkpoint.Curr Opin Cell Biol.2002,14(2):237-245.
[80]Malty A,Mckenna WG,Muschel RJ.The molecular basis for cell cycle delays following ionizing radiation:a review.Radiother Oncol.1994,31(1):1-13.
[78]Sang QXA.Complex role of matrix metalloproteinases in angiogenesis.Cell Res,1998,8(2):171-177.
[79]Yang X,Staten ED,Howard JM,et al.Invasiveness and MMP expression in pancreatic carcinoma.J Surg Res.2001;98(1):33-9.
[80]Jimenez RE,Hartwig W,Antoniu BA,et al.Effect of matrix metalloproteinase inhibition on pancreatic cancer invasion and metastasis:an additive strategy for cancer control.Ann Surg.2000;231(5):644-54.
[81]Hirai H,Maru Y,Hagiwara K,et al.A novel putative tyrosine kinase receptor encoded by the eph gene.Science,1987;238(4834):1717-1720.
[82]Wu Q,Suo Z,Kristensen GB,et al.The prognostic impact of EphB2/B4 expression on patients with advanced ovarian carcinoma.Gynecol Oncol.2006;102(1):15-21.
[83]Wu Q,Suo Z,Risberg B,et al.Expression of Ephb2 and Ephb4 in breast carcinoma.Pathol Oncol Res.2004;10(1):26-33.
[84]Nakada M,Niska JA,Tran NL,et al.EphB2/R-Ras signaling regulates glioma cell adhesion,growth,and invasion.Am J Pathol.2005;167(2):565-76.
[85]Nakada M,Niska JA,Miyamori H,et al.The phosphorylation of EphB2 receptor regulates migration and invasion of human glioma cells.Cancer Res.2004;64(9):3179-85.
[86]Huusko P,Ponciano-Jackson D,Wolf M,et al.Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer.Nat Genct.2004;36(9):979-83.
[87]Lugli A,Spichtin H,Maurer R,et al.EphB2 expression across 138 human tumor types in a tissue microarray:high levels of expression in gastrointestinal cancers.Clin Cancer Res.2005;11(18):6450-8.
1.Miyamori H,Takino T,Kobayashi Y,et al.Claudin promotes activation of pro-matrix metalloproteinase-2 mediated by membrane-type matrix metalloproteinases.J Biol Chem.2001;276:28204-11.
2.Nakada M,Niska JA,Miyamori H,et al.The phosphorylation of EphB2 receptor regulates migration and invasion of human glioma cells.Cancer Res.2004;64(9):3179-85.
3.Pebernard S,Iggo RD.Determinants of interferon-stimulated gene induction by RNAi vectors.Differentiation.2004;72(2-3):103-11.
[1]Zhang B.Wang ZF.Tang MZ,et al.Growth inhibition and apoptosis-induced effect on human cancer cells of toosendanin,a triterpenoid derivative from chinese traditional medicine.Investigational New Drugs.2005,23(6):547-553.
[2]Jiang J.Slivova V.Harvey K,et al.Ganoderma lucidum suppresses growth of breast cancer cells through the inhibition of Akt/NF-kappaB signaling.Nutrition & Cancer,2004,49(2):209-216.
[3]郑丽端,童强松,吴翠环,等.姜黄素诱导卵巢癌细胞株A2780细胞周期阻滞和凋亡.华中科技大学学报(医学版).2003,32(2):209-214.
[4]单保恩,付小梅,华正祥,等.中药五加皮提取成分抗肿瘤活性作用机理研究.中国中西医结合 杂志,2005,25(9):825-828.
[5]李学松,梁云燕,王代树,等.复方中药紫龙金对前列腺癌细胞系LNCaP的体外作用.中国中西医结合杂志,2004,24(7):621-624.
[6]张大鹏,孔棣.回生口服液对人结肠癌THC8908细胞抑制作用.华西医学,2005,20(2):338-339.
[7]熊鹰,孔小云,陈如山,等.复方犀黄丸含药血清对人肝癌细胞生长及其周期影响的实验研究.中国中医药科技.2001,8(4):217-218.
[8]Cheng YL.Chang WL.Lee SC,et al.Acetone extract of Angelica sinensis inhibits proliferation of human cancer cells via inducing cell cycle arrest and apoptosis.Life Sciences,2004,75(13):1579-1594.
[9]Hsu YL.Kuo PL.Lin CC.The proliferative inhibition and apoptotic mechanism of Saikosaponin D in human non-small cell lung cancer A549 cells.Life Sciences,2004,75(10):1231-1242.
[10]Kuo YC.Lin YL.Huang CP,et al.A tumor cell growth inhibitor from Saposhnikovae divaricata.Cancer Investigation,2002,20(7-8):955-64.
[11]曾小莉,涂植光.端粒酶在人参皂甙Rh2诱导肝癌细胞分化中的作用.癌症,2004,23(12):1655-1659.
[12]邓惠,罗焕敏,黄丰,等.苦参碱对C6胶质瘤细胞的增殖和原癌基因表达的影响.中药材,2004,27(6):416-419.
[13]Hsieh TC.Kunicki J.Darzynkiewicz Z,et al.Effects of extracts of Coriolus versicolor (I'm-Yunity) on cell-cycle progression and expression of interleukins-1 beta,-6,and-8 in promyelocytic HL-60 leukemic cells and mitogenically stimulated and nonstimulated human lymphocytes.Journal of Alternative & Complementary Medicine,2002,8(5):591-602.
[14]Hsieh TC.Wu JM.Differential control of growth,cell cycle progression,and gene expression in human estrogen receptor positive MCF-7 breast cancer cells by extracts derived from polysaccharopeptide I'm-Yunity and Danshen and their combination.International Journal of Oncology,2006,29(5):1215-1222.
[15]Moon SK.Jin HS.Ko CN,et al.Inhibition of human endothelial cell proliferation by Gami—Jeonggi—San(Jiawei—Zhenqi—San) is accompanied by transcriptional up-regulation of p53 and Waf1 tumor suppressor genes.Journal of Ethnopharmacology.2005,100(1-2):187-92.
[16]Li KS.Gu XF.Li P,et al.Effect of pseudolaric acid B on gastric cancer cells:inhibition of proliferation and induction of apoptosis.World Journal of Gastroenterology,2005,11(48):7555-7559.
[17]Hsieh TC.Wijeratne EK.Liang JY,et al.Differential control of growth,cell cycle progression,and expression of NF-kappaB in human breast cancer cells MCF-7,MCF-10A,and MDA-MB-231 by ponicidin and oridonin diterpenoids from the chinese herb Rabdosia rubescens.Biochemical & Biophysical Research Communications,2005,337(1):224-231.
[18]Lu QY.Jin YS.Zhang Q,et al.Ganoderma lucidum extracts inhibit growth and induce actin polymerization in bladder cancer cells in vitro.Cancer Letters,2004,216(1):9-20.
[19]Campbell MJ.Hamilton B.Shoemaker M,et al.Antiproliferative activity of Chinese medicinal herbs on breast cancer cells in vitro.Anticancer Research,2002,22(6C):3843-3852.
[20]Chang WH.Chen CH.Lu FJ.Different effects of baicalein,baicalin and wogonin on mitochondrial function,gintathione content and cell cycle progression in human hepatoma cell lines.Planta Medica,2002,68(2):128-132.
[21]杨萍,于廷曦,黄来珍,等.土贝母皂苷诱导人宫颈癌HeLa细胞周期阻滞和细胞凋亡.癌症,2002,21(4):346-350.
[22]张艰,戚好文,吴昌归,等.姜黄素对A549人肺腺癌细胞增殖抑制作用及其机制的研究.中药材,2004,27(12):923-927.
[23]鲍英,夏璐,袁耀宗,等.康莱特对Patu28988细胞周期及其调节基因表达的影响.胰腺病学,2004,4(2):82-85.
[24]徐力,王明艳,许冬青,等.三物白散加味方影响肿瘤细胞周期实验研究.陕西乒医,2005,26(11):1246-1248.
[25]Yao R.Han Z.Wang M,et al.Extract from Arca granosa L inhibits proliferation of human tumout cell lines with kidney and lung origin.Journal of International Medical Research,2006,34(4):355-361.
[26]李宝元,梁云燕,王代树.中药白龙片与HMBA对人胃癌不同周期细胞癌基因与抑癌基因表达调控的共性研究.中国中西医结合杂志,2001,21(4):286-289.
[1]Hirai H,Maru Y,Hagiwara K,et al.A novel putative tyrosine kinase receptor encoded by the eph gene.Science,1987;238(4834):1717-1720.
[2]Kiyokawa E,Takai S.Overexpression of ERK,an Eph family receptor protein tyrosine kinase,in various human tumors.Cancer Research,1994:54(14):3645-3650.
[3]Mellott DO,Burke RD.The molecular phylogeny of eph receptors and ephrin ligands.BMC Cell Biol.2008;9:27.
[4]Lugli A,Spichtin H,Maurer R,et al.EphB2 expression across 138 human tumor types in a tissue microarray:high levels of expression in gastrointestinal cancers.Clin Cancer Res.2005;11(18):6450-8.
[5]Guo DL,Zhang J,Yuen ST,et al.Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumours.Carcinogenesis.2006 Mar;27(3):454-64.
[6]Oba SM,Wang YJ,Song JP,et al.Genomic structure and loss of heterozygosity of EPHB2 in colorectal cancer.Cancer Lett.2001;164(1):97-104.
[7]Kokko A,Laiho P,Lehtonen R,et al.EPHB2 germline variants in patients with colorectal cancer or hyperplastic polyposis.BMC Cancer.2006;6:145.
[8]Liu W,Abroad SA,Jung YD,et al.Coexpression of ephrin-Bs and their receptors in colon carcinoma.Cancer.2002;94(4):934-9.
[9]Clevers H,Batlle E.EphB/EphrinB receptors and Wnt signaling in colorectal cancer.Cancer Res.2006;66:2-5.
[10]Jubb AM,Zhong F,Bheddah S,et al.EphB2 is a prognostic factor in colorectal cancer.Clin Cancer Res.2005 Jul 15;11(14):5181-7.
[11]Oshima T,Akaike M,Yoshihara K,et al.Overexpression of EphA4 gene and reduced expression of EphB2 gene correlates with liver metastasis in colorectal cancer.Int J Oncol.2008;33(3):573-7.
[12]Wu Q,Suo Z,Kristensen GB,et al.The prognostic impact of EphB2/B4 expression on patients with advanced ovarian carcinoma.Gynccol Oncol.2006;102(1):15-21.
[13]Wu Q,Suo Z,Risberg B,et al.Expression of Ephb2 and Ephb4 in breast carcinoma.Pathol Oncol Res.2004;10(1):26-33.
[14]Nakada M,Niska JA,Tran NL,et al.EphB2/R-Ras signaling regulates glioma cell adhesion, growth,and invasion.Am J Pathol.2005;167(2):565-76.
[15]Nakada M,Niska JA,Miyamori H,et al.The phosphorylation of EphB2 receptor regulates migration and invasion of human glioma cells.Cancer Res.2004;64(9):3179-85.
[16]Huusko P,Ponciano-Jackson D,Wolf M,et al.Nonsense-mediated decay mieroarray analysis identifies mutations of EPHB2 in human prostate cancer.Nat Genet.2004;36(9):979-83.
[17]Tang XX,Brodeur GM,Campling BG,et al.Coexpression of transcripts encoding EPHB receptor protein tyrosine kinases and their ephrin-B ligands in human small cell lung carcinoma.Clin Cancer Res.1999;5(2):455-60.
[18]Hafner C,Schmitz G,Meyer S,et al.Differential gene expression of Eph receptors and ephrins in benign human tissues and cancers.Clin Chem.2004;50(3):490-9.
[19]Kataoka H,Tanaka M,Kanamori M,et al.Expression profile of EFNB1,EFNB2,two ligands of EPHB2 in human gastric cancer.J Cancer Res Clin Oncol.2002;125(7):343-8.
[20]Mao W,Luis E,Ross S,et al.EphB2 as a therapeutic antibody drug target for the treatment of colorectal cancer.Cancer Res.2004;64(3):781-8.
[21]Chrencik JE,Brooun A,Recht MI,et al.Three-dimensional structure of the EphB2 receptor in complex with an antagonistic peptide reveals a novel mode of inhibition.J Biol Chem.2007;282(50):36505-13.