鼻咽癌中环氧化酶-2和LMP1的表达和相互关系的初步研究
|
摘要
背景和目的:鼻咽癌是一种常见的头颈部恶性肿瘤,世界卫生组织统计大约有80%的鼻咽癌发生于我国,鼻咽癌具有浸润和转移的特征。颈淋巴结转移为首发症状者占60%,98%的病理类型为低分化鳞状细胞癌。研究表明:环氧化酶—2(Cyclooxygenase-2)是催化前列腺素合成的限速酶,它和恶性肿瘤组织中前列腺素合成有关,在多种肿瘤的发生、发展、淋巴结转移中起重要作用。研究表明:EB病毒和鼻咽癌发生密切相关。其中,EB病毒DNA表达的潜伏膜蛋白1(Epstein-Barrvitus latent membrane protein-1,LMP1)具有多种生物学功能,是其主要的致癌因子。当前研究表明:COX-2、LMP1在鼻咽癌组织中存在高表达,但它们的相互关系如何,尚待进一步研究。本研究运用免疫组化技术检测了53例鼻咽癌组织中的COX-2、LMP1的表达情况,同时分析了两者之间的关系。
材料和方法:53例鼻咽癌常规石蜡标本由浙江大学医学院附属邵逸夫医院病理科提供,为2000—2005年鼻咽癌活检标本,经HE染色确诊为鼻咽癌。其中男性24例,女性29例,年龄为18—81岁,平均年龄52岁。伴有淋巴结转移者38例,无淋巴结转移者15例。病理分型:角化型鳞状细胞癌4例,非角化性鳞状细胞癌27例,未分化癌22例。分期根据97UICC标准:T_1 14例,T_2 14例,T_314例,T_411例;N_015例,N_122例,N_211例,N_35例;Ⅰ期5例,Ⅱ期14例,Ⅲ期19例,Ⅳ期15例。8例鼻咽部慢性炎症常规石蜡切片标本也由浙江大学医学院附属邵逸夫医院病理科提供,HE染色确诊为鼻咽部慢性炎症,其中男性5例,女性3例,作为对照组。所有标本均经10%中性甲醛固定,石蜡包埋,5um连续切片,用SP免疫组化法检测COX-2、LMP1的表达,用SPSS12.0统计软件对实验数据进行统计。
结果:1在鼻咽癌组织中,COX-2阳性表达率为71.70%(38/53);LMP1阳性表达率为66.04%(35/53)。
2 COX-2、LMP1的表达在鼻咽癌颈部淋巴结转移组中均明显高于无颈部淋巴结转移组(P＜0.05),但在年龄、性别、病理类型、临床分期的分组中均无显著性差异(P＞0.05)。
3在鼻咽癌组织中,LMP1和COX-2的表达存在正相关(r=0.797,P＜0.001)。
结论:1 COX-2、LMP1在鼻咽癌组织中均有表达。
2 COX-2、LMP1在鼻咽癌中的表达和鼻咽癌颈淋巴结转移存在显著相关性,但和年龄、性别、病理类型、临床分期无相关性。
3 COX-2和LMP1在鼻咽癌组织中的表达呈正相关。LMP1可能通过多途径上调COX-2的表达,从而促进鼻咽癌颈部淋巴结转移。
Background and Objective:Nasopharyngeal carcinoma(NPC)is the most common one of malignant tumor in head and neck.According to WHO statistics,80%of them happened in China.Nasopharyngeal carcinoma is characterized with infiltrating and metastasis.60%NPC patients have been founded with neck lymphatic metastasis at their first examination.98%NPC is poorly differentiated squamous cell carcinoma.Studies have demonstrated that cyclooxygenase-2(COX-2)is the rate-limiting enzyme prostaglandin, concerned with prostagland in synthetical and played an essential role in many tumors' genesis,growth and lymph nodes metastasis.Studies have demonstrated the relationship between NPC and Epstein-Barr vitus(EBV) infection.Epstein-Barr vitus latent membrane protein-1(LMP1)is the primary carcinogen with multiple biological functions.Previous studies had demonstrated that NPC can express COX-2,LMP1 highly,but their association were not very clearly.In our experiment,the expressions of COX-2 and LMP1 were immunohistochemically studied in 53 NPC sections,we wanted to know the correlation between COX-2,LMP1 in NPC.
Materials and Methods:53 nasopharynx biopsy specimens from patients with NPC who had been diagnosed definitely by pathology from Sir Run Run Shaw Hospital,Medical School of Zhejiang University from 2000 to 2005.The specimens included 24 male and 29 female patients(age ranged from 18 to 81 years old,mean age was 52 years old).Neck lymph nodes metastasis in these patients was 38 cases,and none neck lymph nodes metastasis was 15 ones. Pathological classification:Keratinizing squamous cell carcinoma was 4 cases,nonkeratinizing squamous cell carcinoma 27,and undifferentiated carcinoma 22.Accordong to 1997 UICC classification,T_1 was 14 cases,T_2 14 cases,T_3 14 cases and T_4 11 cases;N_0 was 15 cases,N_1 22 cases,N_2 11 cases and N_3 5 cases;StageⅠwas 5cases,Ⅱ14 cases,Ⅲ19 cases andⅣ15 cases. 8 nasopharyngeal biopsy specimens were collected from patients with chronic nasopharyngeal who had been diagnosed definitely by HE stain in the same hospital(male 5 and female 3),which were served as normal controls.All these tissue samples were fixed in 10%formaJdehyde solution after being obtained, then embedded in paraffin,5-micrometer thick sections were prepared for examining the expression of COX-2,LMP1 by streptavidin-peroxidase immunochemistry.All the datas were analyzed statistically with SPSS 12.0 software in computer.
Result:1.In Nasopharyngeal carcinoma tissue,Positive expression rate of COX-2 was 71.70%(38/53);Positive expression rate of LMP1 was 66.04%(35/53)。
2.In Nasopharyngeal carcinoma tissue,there was significant relation of COX-2,LMP1 with N stage(P＜0.05), none-significant ralation of COX-2,LMP1 with age,ender, tumor stage,clinical stage and pathological classification(P＞0.05).
3.In Nasopharyngeal carcinoma tissue,the expression of COX-2 showed a significant positive correlation with the expression of LMP1(r=0.797,P＜0.001)。
Conclusion:1.The results suggested that COX-2,LMP1 were highly expressed in nasopharyngeal carcinoma cells.
2.The expressions of COX-2、LMP1 were significantly associated with neck lymph nodes metastasis. none-significant ralation of COX-2,LMP1 with age,gender、tumor stage,clinical stage and pathological classification.
3.The expression of LMP1 showed a significant positive correlation with the expression of COX-2,and it showed that LMP1 could enhance NPC metastasis by up-regulating the expression of COX-2.
材料和方法:53例鼻咽癌常规石蜡标本由浙江大学医学院附属邵逸夫医院病理科提供,为2000—2005年鼻咽癌活检标本,经HE染色确诊为鼻咽癌。其中男性24例,女性29例,年龄为18—81岁,平均年龄52岁。伴有淋巴结转移者38例,无淋巴结转移者15例。病理分型:角化型鳞状细胞癌4例,非角化性鳞状细胞癌27例,未分化癌22例。分期根据97UICC标准:T_1 14例,T_2 14例,T_314例,T_411例;N_015例,N_122例,N_211例,N_35例;Ⅰ期5例,Ⅱ期14例,Ⅲ期19例,Ⅳ期15例。8例鼻咽部慢性炎症常规石蜡切片标本也由浙江大学医学院附属邵逸夫医院病理科提供,HE染色确诊为鼻咽部慢性炎症,其中男性5例,女性3例,作为对照组。所有标本均经10%中性甲醛固定,石蜡包埋,5um连续切片,用SP免疫组化法检测COX-2、LMP1的表达,用SPSS12.0统计软件对实验数据进行统计。
结果:1在鼻咽癌组织中,COX-2阳性表达率为71.70%(38/53);LMP1阳性表达率为66.04%(35/53)。
2 COX-2、LMP1的表达在鼻咽癌颈部淋巴结转移组中均明显高于无颈部淋巴结转移组(P＜0.05),但在年龄、性别、病理类型、临床分期的分组中均无显著性差异(P＞0.05)。
3在鼻咽癌组织中,LMP1和COX-2的表达存在正相关(r=0.797,P＜0.001)。
结论:1 COX-2、LMP1在鼻咽癌组织中均有表达。
2 COX-2、LMP1在鼻咽癌中的表达和鼻咽癌颈淋巴结转移存在显著相关性,但和年龄、性别、病理类型、临床分期无相关性。
3 COX-2和LMP1在鼻咽癌组织中的表达呈正相关。LMP1可能通过多途径上调COX-2的表达,从而促进鼻咽癌颈部淋巴结转移。
Background and Objective:Nasopharyngeal carcinoma(NPC)is the most common one of malignant tumor in head and neck.According to WHO statistics,80%of them happened in China.Nasopharyngeal carcinoma is characterized with infiltrating and metastasis.60%NPC patients have been founded with neck lymphatic metastasis at their first examination.98%NPC is poorly differentiated squamous cell carcinoma.Studies have demonstrated that cyclooxygenase-2(COX-2)is the rate-limiting enzyme prostaglandin, concerned with prostagland in synthetical and played an essential role in many tumors' genesis,growth and lymph nodes metastasis.Studies have demonstrated the relationship between NPC and Epstein-Barr vitus(EBV) infection.Epstein-Barr vitus latent membrane protein-1(LMP1)is the primary carcinogen with multiple biological functions.Previous studies had demonstrated that NPC can express COX-2,LMP1 highly,but their association were not very clearly.In our experiment,the expressions of COX-2 and LMP1 were immunohistochemically studied in 53 NPC sections,we wanted to know the correlation between COX-2,LMP1 in NPC.
Materials and Methods:53 nasopharynx biopsy specimens from patients with NPC who had been diagnosed definitely by pathology from Sir Run Run Shaw Hospital,Medical School of Zhejiang University from 2000 to 2005.The specimens included 24 male and 29 female patients(age ranged from 18 to 81 years old,mean age was 52 years old).Neck lymph nodes metastasis in these patients was 38 cases,and none neck lymph nodes metastasis was 15 ones. Pathological classification:Keratinizing squamous cell carcinoma was 4 cases,nonkeratinizing squamous cell carcinoma 27,and undifferentiated carcinoma 22.Accordong to 1997 UICC classification,T_1 was 14 cases,T_2 14 cases,T_3 14 cases and T_4 11 cases;N_0 was 15 cases,N_1 22 cases,N_2 11 cases and N_3 5 cases;StageⅠwas 5cases,Ⅱ14 cases,Ⅲ19 cases andⅣ15 cases. 8 nasopharyngeal biopsy specimens were collected from patients with chronic nasopharyngeal who had been diagnosed definitely by HE stain in the same hospital(male 5 and female 3),which were served as normal controls.All these tissue samples were fixed in 10%formaJdehyde solution after being obtained, then embedded in paraffin,5-micrometer thick sections were prepared for examining the expression of COX-2,LMP1 by streptavidin-peroxidase immunochemistry.All the datas were analyzed statistically with SPSS 12.0 software in computer.
Result:1.In Nasopharyngeal carcinoma tissue,Positive expression rate of COX-2 was 71.70%(38/53);Positive expression rate of LMP1 was 66.04%(35/53)。
2.In Nasopharyngeal carcinoma tissue,there was significant relation of COX-2,LMP1 with N stage(P＜0.05), none-significant ralation of COX-2,LMP1 with age,ender, tumor stage,clinical stage and pathological classification(P＞0.05).
3.In Nasopharyngeal carcinoma tissue,the expression of COX-2 showed a significant positive correlation with the expression of LMP1(r=0.797,P＜0.001)。
Conclusion:1.The results suggested that COX-2,LMP1 were highly expressed in nasopharyngeal carcinoma cells.
2.The expressions of COX-2、LMP1 were significantly associated with neck lymph nodes metastasis. none-significant ralation of COX-2,LMP1 with age,gender、tumor stage,clinical stage and pathological classification.
3.The expression of LMP1 showed a significant positive correlation with the expression of COX-2,and it showed that LMP1 could enhance NPC metastasis by up-regulating the expression of COX-2.
引文
[1]郭颖,方媾.鼻咽癌遗传学的研究进展[J].癌症,1998,17(4):316-318.
[2]Daxies G,Salter J,Hills M,et al.Coorelation between cyclooxygenase-2 expression and angiogenesis in human breast cancer[J].Clin Cancer Res.2003,9(7):2651-2656.
[3]Harris R C,Mckanna J A,Akai Y,et al.Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restrixtion.J Clin Invest,1994,94(6):2504.
[4]Stephen MP,Prescott FA.Cyclooxygenase-2 and carcinogenesis.Biochim Biophys Acta,2000,1470M69-M78.
[5]Oshima M,Dinchuk Je,Kargman SL,et al.Suppression of intestinal polyposis in Apc delta 716 knockout micc by inhibition of cyclooxygenase-2(COX-2).Cell,1996,87:803-809.
[6]Tsujii M,Dubios RN.Alterlations is cellular adhesion and apoptosis in epithelial cells overexpression COX-2.Cell,1995,83:493.
[7]Fahraeus R,then W,Truvedi P,et al.Decreased expression of E-cadherin and increased invasive capacity in EBV-LMP-transfected human epithelial and murine adenocarcinoma cells[J].Int J Cancer,1992,52(5):834.
[8]李智,宗永生.鼻咽癌组织中LMP-1的表达对癌细胞增殖和凋亡的影响[J].中华病理学杂志,1999,28(5):21.
[9]罗容珍,钟碧玲,宗永生,等.高发区鼻咽癌病理组织学类型构成的特点[J].中国肿瘤,2001,10(8):473.
[10]Knox PG,Li QX,Rickinson AB,et al.In vitro production of stable Epstein-Barr virus-positive epithelial cell clones which resemble the virus-cell interaction observed in nasopharyngeal carcinoma[J].Virology,1996,215:40.
[11]Teramoto N,Maeda A,Kobayashi K,et al.Epstein-Barr vitus infection to Epstein-Barr virus-negative nasooharyngeal carcinoma cell line TWO3 enhances its tumorigenicity.Lab Invest,2000,80(3):303-312.
[12]李玉林,唐建武主编.病理学,第6版.北京:人民卫生出版社,2005:180.
[13]Dong Y,Sui L,Watanabe Y,et al.Survivin expression in laryngeal squamous cell carcinoma and its prognostic imlication[J].Anticancer Res,2002,22:2377-2383.
[14]Soslow RA,Dannenberg AJ,Rush D,et al.COX-2 is expressed in human pulmomary,colonic,and mammary tumors[J].Cancer,2000,89(12):2637-2645.
[15]Williams CS,et al.Prostaglandin endoperoxide synthese:Why two isoforms? Am J Physiol,1996,270(3Pt1):6393-400
[16]Lindsay M.Shafer,Lee W.Slice.Anisomycin induces COX-2 mRNA expression through P38MAPK and CREB independent of small GTPases in intestinal epithelial cells.Biochimica et Biophysica Acta 1745(2005)393-400
[17]lecomet M,Laneuville Q,Ji C,et al.Acetylation of human prostagland in-endoperoxid synthase-2 by aspirin.J Biol them,1994,269:13207
[18]Kazuhito Tatsu,et al.Cyclooxygenase-2 in sporiadic colorectal polyps:Immunohistochemical study and its importance in the early stsges of colorectal tumorigenesis.Pathology-Research and Practice,201(2005)427-433
[19]Masferrer Jh,leahy KM,Koki AT,et al.Antiangiogenic and antitumor activities of eyclooxygenase-2 inhibitors[J].Can Res,2000,60(5):1306-1311
[20]You-Cheng Hseu,et al.Anti-inflammatory potential of Antrodia Camphorata through inhibition of iNOS,COX-2 and cytokines via the NF-κB pathway.Intemational Immunopharmacology 5(2005)1914-1925
[21]Mark A.Hull.Cyclooxygenase-2:How good is it as a target for cancer chemoprevention? European Journal of Cancer 41(2005)1854-1863
[22]T HIa,K Neilson.Human cyclooxygenase-2 cDNA.Proc Natl Acad Sci USA,1992,89:7384-7388
[23]Wei Liu,Steven Dubinett,Simie Lavern A.Patterson,Kathleen A.Kelly.COX-2inhibition affects growth rate of Chlamydia muridarum within epithelial cells.Microbes and Infection(2005)2626-2635
[24]Lucrecia Ma'rquez-Rosado,et al.Celecoxib,a cyclooxygenase-2 inhibitor,prevents induction of liver preneoplastic lesions in rats.Journal of Hepatology 43(2005)653-660
[25]Andreas D.Ebert,Julia Bartley,Matthias David.Aromatase inhibitors and cyclooxygenase-2(COX-2)inhibitors in endometriosis:New questions—old answers?European Journal of Obstetrics & Gynecology and Reproductive Biology 122(2005)144-150
[26]Langenbach R,Loftin Ch.Cyclooxygenase knockout mice models for elucidating isoform-specific functions.Biochem Pharmacol,1999,58(8):1237-1246
[27]Ridley SH,Sarsfieid SJ,Lee Je,et al.Actions of IL-1 are selectively controlled by P38 mitogen-actived protein kinase.J Immunol,1997,158:3165
[28]Jen-Hao Chen,et al.Effects of COX-2 inhibitor on growth of human gastric cancer cells and its relation to hepatocyte growth factor.Cancer Letters 12(2005)1-8
[29]Mei-Hua Li,Jung-Hee Jang,Young-Joon Surh.Nitric oxide induces apoptosis via AP-1 driven upregulation of COX-2 in rat pheochromocytoma cells.Free Radical Biology &Medicine 39(2005)890-899
[30]Vattoly J.Majo,et al.A general method for the synthesis of aryl[11C]methylsulfones:Potential PET probes for imaging cyclooxygenase-2expression.Bioorg.Med.Chem.Lett,15(2005)4268-4271
[31]Guang-Zhi Yang,Li Li,Hua-Ye Ding,Jin-Song Zhou.Cyclooxygenase-2 is over-expressed in Chinese esophageal squamous cell carcinoma,and correlated with NF-κB:An immunohistochemical study.Expreimetal and Moleculal Pathlogy 79(2005)214-218
[32]蒋代华,郭德玉,刘友生等.环氧化酶-2在肿瘤研究中的应用进展.临床医药杂志,2004:17(1)32-34
[33]Gallo O,Masini E,Bianchi B,et al.Hum Pathol,2002,33(7):708-714
[34]Tan KB,Putti TC.Cyclooxygenase-2 expression in nasopharyngeal carcinoma:immunohistochemical findings and potential implications.J ClAn Pathol,2005,58(5):545-538
[35]Soo R,Putti T,Tao Q,et al.Overexpression of cyclooxygenase-2 in nasopharyngeal carcinoma and associstion with epidermal growth factor receptor expression.Arch Otolaryngol Head Neck Surg,2005,131(2):147-152
[36]Nathan CA,Leskov IL,Lin N,et al.CoX-2 expression in dysplasia of the head and neck correlation with eIF4e.Cancer,2001,9(7):1888-1895
[37]Chen WC,McBride WH,Chen SM,et al.Prediction of poor survival by cyclooxygenase-2in patients with T_4 nasopharyngeal cancer treated by radiation therapy:clinical and in vitro studies.Head Neck,2005,27(6):503-512
[38]马长春、李德锐等.EB病毒潜伏膜蛋白1的基础研究进展与临床意义.汕头大学医学院学报,2004.17:62-64
[39]胡利福.EBV标码的潜伏膜蛋白.癌症,2002,21:559-566
[40]李智,宗永生.鼻咽癌组织中潜伏膜蛋白1的表达对癌细胞增殖和凋亡的影响.中华病理学杂志,1999,28(5):340-343.
[41]Murono S,Yoshizaki T,Park CS.Association of Epstein-Barr vitus infection with p53 protein accumulation but not bcl-2 protein in nasopharngeat carcinoma.Histopathology,1999,34(5):432-438.
[42]Eliopoulos AG,Waites ER,Blake SM,et al.TRAF1 is a critical regulator of JNK signaling by the TRAF-binding domain of the Epstein-Barr virus-encoded latent infection membrance protein 1 but not CD40.J Viros,2003,77(2):1316-1328.
[43]Godd JD,Salisbury JR,Packham G,et al.A20 RNA expression is associated with undeferentiated nasopharygeal carcinoma and poorly differentiated head and neck squamous cell carcinoma.J Pathol,1999,187(5):549-555.
[44]王承兴,邓锡云,李小艳,等.EB病毒LMP1在鼻咽癌绌胞系中通过NF-κB、AP-1促进MMP9表达.中华肿瘤杂志,2002,24(1):9-13.
[45]Yoshizaki T.Promotion of metastasis in nasopharngeal carcinoma by Epstein-Barr vitus latent membrane protein-1.Histol Histopathol,2002,17(3):845-850.
[46]蔡朝阳,汤建国,李旋,等.基质金属蛋白酶-9和IL8在鼻咽癌中的表达及其与潜伏膜蛋白1的相关性研究.临床耳鼻咽喉头颈外科杂志,2007,21(21):966-969.
[47]Murono S,Inone H,Tanabe T,et al.Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor in nasopharyngeal carcinoma cell.Proc Natl Acad Sci LSA,2001,98(12):6905-6910.
[48]Aeckel EC,Naja S,Tan J,et al.Correlation of expression of cyclooxygenase-2,Vasular endothelial growth factor,and peroxisome proliferator-activated receptor delta with head and neck squamous cell carcinoma.Arch Otolaryngol Head Neck Surg,2001,127(10):1253-1259.
[1]Yoshimura R, Sano H, Masuda C, et al. Expression of cyclooxygenase-2 in prostate carcinoma [J]. Cancer, 2000, 89(3): 589-596
[2]Williams CS, et al. Prostaglandin endoperoxide synthese: Why two isoforms? Am J Physiol, 1996, 270(3 Pt 1): G393-400
[3]Lindsay M. Shafer, Lee W. Slice. Anisomycin induces COX-2 mRNA expression through P38MAPK and CREB independent of small GTPases in intestinal epithelial cells. Biochimica et Biophysica Acta 1745(2005)393-400
[4]lecomet M, Laneuville Q, Ji C, et al. Acetylation of human prostagland in-endoperoxid synthase-2 by aspirin. J Biol Chem, 1994, 269: 13207
[5]Kazuhito Tatsu, et al. Cyclooxygenase-2 in sporiadic colorectal polyps: Immunohistochemical study and its importance in the early stsges of colorectal tumorigenesis. Pathology-Research and Practice, 201(2005)427-433
[6]Masferrer JL, leahy KM, Koki AT, et al. Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors [J]. Can Res, 2000, 60(5): 1306-1311
[7]You-Cheng Hseu, et al. Anti-inflammatory potential of Antrodia Camphorata through inhibition of iNOS, COX-2 and cytokines via the NF-κB pathway. International Immunopharmacology 5 (2005) 1914-1925
[8]Mark A. Hull. Cyclooxygenase-2: How good is it as a target for cancer chemoprevention? European Journal of Cancer 41 (2005) 1854 - 1863
[9]T HIa, K Neilson. Human cyclooxygenase-2 cDNA. Proc Natl Acad Sci USA, 1992, 89: 7384-7388
[10]Vezza R, Habib A, Li H, et al. Regulation of cyclooxygenases by protein Kinase C. Evidence against the importance of direct enzyme phosphorylation. J Biol Chem, 1996, 271: 30028-30033
[11]MillerC, Zhang M, He Y, et al. Transcriptional induction of cyclooxygenase-2 gene by okadaic acid inhibition of Phosphatase activity in human chondrocytes: Co-stimulation of AP-1 and CRE nuclear binding proteins. J Cell Biochen, 1998, 69(4): 392-413
[12]M Gophelt-Struebe, A Huhn, M Stroebel, et al. Independent regulation of cyclooxygenase-2 expression by p42/44 mitogen-activated protein kinases and Ca2+/calmodulin-dependent kinase. Biochem J, 1999, 339: 329-334
[13]WW Lin, B Chen. Induction of cyclooxyenase-2 expression by nethyl arachidonyl fluorophosphonate in murine J774 macrophages: roles of protein kinase C, ERKs and p38 MAPK. Br J Pharmacol, 1999, 126: 1419-1425
[14]Sheng HM, Shao TY, Dubois RN. K-Ras-mediated increase in cyclooxygenase-2 mRNA stability involves activation of the protein Kinase B. Cancer Res, 2001, 61(6): 2670-2675
[15]Wei Liu, Steven Dubinett, Simie Lavern A. Patterson, Kathleen A. Kelly . COX-2 inhibition affects growth rate of Chlamydia muridarum within epithelial cells. Microbes and Infection (2005) 2626-2635
[16]Lucrecia Ma'rquez-Rosado, et al. Celecoxib, a cyclooxygenase-2 inhibitor, prevents induction of liver preneoplastic lesions in rats. Journal of Hepatology 43 (2005) 653 - 660
[17]Andreas D. Ebert, Julia Bartley, Matthias David. Aromatase inhibitors and cyclooxygenase-2 (COX-2) inhibitors in endometriosis: New questions-old answers? European Journal of Obstetrics & Gynecology and Reproductive Biology 122 (2005) 144-150
[18]Langenbach R,Loftin Ch.Cyclooxygenase knockout mice models for elucidating isoform-specific functions.Biochem Pharmacol,1999,58(8):1237-1246
[19]Ridley SH,Sarsfieid SJ,Lee Je,et al.Actions of IL-1 are selectively controlled by P38 mitogen-actived protein kinase.J Immunol,1997,158:3165
[20]Jen-Hao Chen,et al.Effects of COX-2 inhibitor on growth of human gastric cancer cells and its relation to hepatocyte growth factor.Cancer Letter 12(2005)1-8
[21]Mei-Hua Li,Jung-Hee JanE,Young-Joon Surh.Nitric oxide induces apoptosis via AP-1 driven upregulation of COX-2 in rat pheochromocytoma cells.Free Radical Biology & Medicine 39(2005)890-899
[22]Vattoly J.Majo,et al.A general method for the synthesis of ary[11C]methylsulfones:Potential PET probes for imaging cyclooxygenase-2 expression.Bioorg.Med.Chem.Lett.15(2005)4268-4271
[23]Olaf Buchweitz,Annette Staebler,Pia Wu ifing,Erik Hauzman,Robert Greb,Ludwig Kiesel.COX-2 overexpression in peritoneal lesions is correlated with nonmenstrual chronic pelvic pain.European Journal of Obstetrics & Gynecology and Reproductive Biology(2005)121-125
[24]Guang-Zhi Yang,Li Li,Hua-Ye Ding,Jin-Song Zhou.Cyclooxygenase-2 is over-expressed in Chinese esophageal squamous cell carcinoma,and correlated with NF-κB:An immunohistochemical study,Expreimetal and Moleculal Pathlogy 79(2005)214-218
[25]Mitchell JA,Akarasereen out P,Thiemermann C,et al.Selectivity of nonsteroidal anti-inflammatony drugs as inhibitors of constitutive and inducible cyclooxygenase[J].Proc Natl Acad Sci USA,1994,90:11693
[26]Engelhardt G,Bogel R,Schnitzer C,et al.Meloxican influence on arachidonic acid metabolism in vitro findings[J].Biochem Pharmacol,1996,51:21
[27]Tsujii M.COX-2 expression in humun colon cancer increases metastatic peotential.Proc Natl Acid Sci USA,1997,94:3336-3340
[28]J.Rubioa,D.Ramos,J.A.Lo'pez-Guerrero,I.Iborra,A.Colladoa,E.Solsona,S.Almenar,A.Llombart-Bosch.Immunohistochemical Expression of Ki-67 Antigen,COX-2and Bax/Bcl-2 in Prostate Cancer.Prognostic value in Biopsies and Radical Prostatectomy Specimens.European Urology 48(2005)745- 751
[29]Helen,H.W,Chert M.D,et al.Incresed expression of nitric oxide synthase and cyclooxygenase-2 is associated with poor survival in cancer treated with radiotherapy,doi:10.1016/j,ijrobp.2005.03.062
[30]Zoshihisa Ohta,Mami Takahashi,Atsushi Ochiai.Increased protein expression of both inducible nitric oxide synthase and cyclooxygenase-2 in human colon cancers.Cancer Letters(2005)1-8
[31]Induction of Angiopoietin-2 gene expression by COX-2:A novel role for COX-2inhibitors during hepatocarcinogenesis.Journal of Hepatology(2005)1-2
[32]Jyh-Ping Peng,Hui-Chiu Chang,Chung-Feng Hwang,Wen-Chun Hung.Overexpression of cyclooxygenase-2 in nasopharyngeal carcinoma and association with lymph node metastasis.Oral Oncology(2005)41,903-908
[33]Tucker,O.N.,Dannenberg,A.J.,Yang,E.K.et al.Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer.Cancer Res,59:987,1999
[34]Elder,D.J.,Halton,D.E.,Playle,L.C.et al.The MEK/ERK pathway mediates COX-2-selective NSAID-induced apoptosis and induced COX-2 protein expression in colorectal carcinoma cells. Int J Cancer, 99: 323, 2002
[35]Eibl, G., Reber, H. A., Wente, M. N. et al. The selective cyclooxygenase-2 inhibitor nimesulide induces apoptosis in pancreatic cancer cells independent of COX-2. Pancreas, 26: 33, 2003
[36]Tardieu, D., Jaeg, J. P., Deloly, A. et al. The COX-2 inhibitor nimesulide suppresses superoxide and 8-hydroxy-deoxyguanosine formation, and stimulates poptosis in mucosa during early colonic inflammation in rats. Carcinogenesis, 21: 937, 2000
[37]Yao, R., Rioux, N., Castonguay, A. et al. Inhibition of COX-2 and induction of apoptosis: two determinants of nonsteroidal anti-inflammatory drugs' chemopreventive efficacies in mouse lung tumorigenesis. Exp Lung Res, 26:731, 2000
[38]Li, M., Wu, X., Xu, X. C. Induction of apoptosis in colon cancer by cyclooxygenase-2 inhibitor NS398 through a cytochrome c-dependent pathway. Clin Cancer Res, 7: 1010, 2001
[39]Li, M., Wu, X., Xu, X. C. Induction of apoptosis by cyclooxygenase-2 inhibitor NS398 through a cytochrome C-dependent pathway in esophageal cancer cells. Int J Cancer, 93: 218, 2001
[40]Tsujii M, et al. Alterations in cellular adhesion and apoptosis inepithelial cells over expressing prostaglandin endospreroxide synthase 2. Cell, 1995, 83: 493-501
[41]Sheng H. Modulation of apoptosis and bcl-2 expression by prostaglantin E_2 in human colon cancer cells. Cancer Res, 1998, 58: 326-336
[42] Jones MK, Wang H, Peskar BM Levin E, Itani RM, sarfdh IJ, Tarnawski AS Inhibition of angiogenesis by nonsteroidal anti-in-flammatory drugs: insight into mechanisms and implications for cancer growth and ulcer healing. Nat Med, 1995, 5: 1418-1423
[43]Gilhooly EM, Rose DP. The association between a mutated ras gene and cyclooxygenase-2 expression in human breast cancer cell lines. 1999,15:267-270
[44]Chan G, Boyle Jo, Yang EK, et al. Mechanisms underlying nonseroidal anti-inflammatory grug-mediated apoptosis. Cancer Res, 1999, 59(5): 991-994
[45]Castonguay A, Rioux N. Inhibition of Lung tumorigenesis by sulindac: comparison of two experimental protocols. 1997, Carcinogenesis 18: 491-496
[46]Lin XH, Yao S, Kirschenbaum A, Levine AC. NS398, a selective cyclooxygenase-2 inhibitor, induces apoptosis, and down-regulates bcl-2 expression in LNCap cells. Cancer Res, 1998, 58: 4245-4249
[47]Tsujii M, kawano S, DuBosi RN. Cyclooxygenase-2 expression in human colon cancer cells increases metastasic potential. Proc Natl Acad Sci USA, 1997, 94: 3336— 3340
[48]Koga H, Sakisaka S, Ohishi M, et al. Expression of COX-2 in human hepatocellular carinoma:releance to tumor dedifferentiation [J]. Hepatolony, 1999, 29(3): 688-696
[49]Stolina M, et al. Specific inhibition of IL-10 and IL-12 synthesis. J Immunol, 2000, 164: 361-370
[50]Kambayashi T. Potential involvement of IL-10 in suppression tumor associated macrophages colon-26-derived PGE_2 inhibits TNP-α release via a mechanism involving IL-10. J Immunol, 154: 3383-3390
[51]Tsutomu, et al. Relation between COX-2 expression and tumor invasiveness and patient survival in transitional cell carcinoma of the urinany bladder. 2001, 92: 188-193
[52]Prescott SM. Intimate connections between APC and prostaglandin H synthase-2 . Cell, 1996,87:783-786
[53]Attiga FA,et al.Effect of the cyclooxygenase-2(COX-2)-selective inhibitor NS398on the secretion of matrix metalloproteinases(MMP-2 and MMP-9)and tissue inhibitors of metalloproteinases(TIMP-1 and TIMP-2)from human prostate tumor cells.Peoc AM Assco Cancer Res,41:131-132
[54]蒋代华,郭德玉,刘友生等.环氧化酶-2在肿瘤研究中的应用进展.临床医药杂志,2004,17(1)32-34.
[55]Gallo O,Masini E,Bianchi B,et al.Hum Pathol,2002,33(7):708-714
[56]Tan KB,Putti TC.Cyclooxygenase-2 expression in nasopharyngeal carcinoma:immunohistochemical findings and potential implications.J ClAn Pathol,2005,58(5):545-538.
[57]Steinbach G,Lynch PM,Philips RK,et al.The effect of celecoxib,a cyclooxegenase-2inhibitor,in familial adenomatous polyposis[J].N Engl J Med,2000,342(26):1946-1952.
[58]Lanza-Jacoby S,Miller S,Flynn J,Gallatig K,et al.The Cyclooxygenase-2 Inhibitor,Celecoxib,Prevents the Development of Mammary Tumors in HER-2/neu Mice[J].Cancer Epidemiol Biomarkers Prey,2003 Dec 1,12(12):1486-1491
[59]Soo R,Putti T,Tao Q,et al.Over expression of cyclooxygenase-2 in nasopharyngeal carcinoma and association with epidermal growth factor receptor expression.Arch Otolaryngol Head Neck Surg,2005,131(2):147-152
[60]Nathan CA,Leskov IL,Lin N,et al.COX-2 expression in dysplasia of the head and neck correlation with eIF4e.Cancer,2001,9(7):1888-1895
[61]Chen WC,McBride WH,then SM,et al.Prediction of poor survival by cyclooxygenase-2in patients with T_4 nasopharyngeal carcer treated by radiation therapy:clinical and in vitro studies.Head Neck,2005,27(6):503-512
[62]邓刚,杨成章,陈望燕.环氧化酶-2与Ki-67在喉鳞状细胞癌中表达的特点及其临床意义.中国现代医学杂志,2005,15(17):2632-2635
[63]Masunaga R,Klhno H,et al.Cyclooxygenase-2 expression correlates with tumor neovacularization and prognosis in human colorectal carcinoma patients[J].Clin Cancer Res,2002,6(10):4064-4068
[64]马长春,李德锐等.EB病毒潜伏膜蛋白l的基础研究进展与临床意义.汕头大学医学院学报,2004,1(17),62-64
[65]胡利福.EBV标码的潜伏膜蛋白[J].癌症,2002,21(5):559-566.
[66]Teramoto N,Maeda A,Kobayashi K,et al.Epstein-Barr vitus infection to Epstein-Barr vitus-negative nasooharyngeal carcinoma cell line TWO_3 enhances its tumorigenicity.Lab Invest,2000,80(3):303-312
[67]李智,宗永生.鼻咽癌组织中潜伏膜蛋白1的表达对癌细胞增殖和凋亡的影响.中华病理学杂志,1999,28(5):340-343
[68]王承兴,邓锡云,李小艳,等.EB病毒LMP1在鼻咽癌细胞系中通过NF-κB、AP-1促进MMP9表达.中华肿瘤杂志,2002,24(1):9-13
[69]Yoshizaki T.Promotion of metastasis in nasopharngeal carcinoma by Epstein-Barr virus latent membrane protein-1.Histol Histopathol,2002,17(3):845-50
[70]Murono S,Inone H,Tanabe T,et al.Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor in nasopharyngeal carcinoma cell.Proc Natl Acad Sci LSA,2001,98(12):6905-6910
[71]Aeckel EC,Raja S,Tan J,et al.Correlation of expression of cyclooxygenase-2,Vasular endothelial growth factor,and peroxisome proliferator-activated receptor delta with head and neck squamous cell carcinoma.Arch Otolaryngol Head Neck Surg,2001,127(10):1253-1259
[2]Daxies G,Salter J,Hills M,et al.Coorelation between cyclooxygenase-2 expression and angiogenesis in human breast cancer[J].Clin Cancer Res.2003,9(7):2651-2656.
[3]Harris R C,Mckanna J A,Akai Y,et al.Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restrixtion.J Clin Invest,1994,94(6):2504.
[4]Stephen MP,Prescott FA.Cyclooxygenase-2 and carcinogenesis.Biochim Biophys Acta,2000,1470M69-M78.
[5]Oshima M,Dinchuk Je,Kargman SL,et al.Suppression of intestinal polyposis in Apc delta 716 knockout micc by inhibition of cyclooxygenase-2(COX-2).Cell,1996,87:803-809.
[6]Tsujii M,Dubios RN.Alterlations is cellular adhesion and apoptosis in epithelial cells overexpression COX-2.Cell,1995,83:493.
[7]Fahraeus R,then W,Truvedi P,et al.Decreased expression of E-cadherin and increased invasive capacity in EBV-LMP-transfected human epithelial and murine adenocarcinoma cells[J].Int J Cancer,1992,52(5):834.
[8]李智,宗永生.鼻咽癌组织中LMP-1的表达对癌细胞增殖和凋亡的影响[J].中华病理学杂志,1999,28(5):21.
[9]罗容珍,钟碧玲,宗永生,等.高发区鼻咽癌病理组织学类型构成的特点[J].中国肿瘤,2001,10(8):473.
[10]Knox PG,Li QX,Rickinson AB,et al.In vitro production of stable Epstein-Barr virus-positive epithelial cell clones which resemble the virus-cell interaction observed in nasopharyngeal carcinoma[J].Virology,1996,215:40.
[11]Teramoto N,Maeda A,Kobayashi K,et al.Epstein-Barr vitus infection to Epstein-Barr virus-negative nasooharyngeal carcinoma cell line TWO3 enhances its tumorigenicity.Lab Invest,2000,80(3):303-312.
[12]李玉林,唐建武主编.病理学,第6版.北京:人民卫生出版社,2005:180.
[13]Dong Y,Sui L,Watanabe Y,et al.Survivin expression in laryngeal squamous cell carcinoma and its prognostic imlication[J].Anticancer Res,2002,22:2377-2383.
[14]Soslow RA,Dannenberg AJ,Rush D,et al.COX-2 is expressed in human pulmomary,colonic,and mammary tumors[J].Cancer,2000,89(12):2637-2645.
[15]Williams CS,et al.Prostaglandin endoperoxide synthese:Why two isoforms? Am J Physiol,1996,270(3Pt1):6393-400
[16]Lindsay M.Shafer,Lee W.Slice.Anisomycin induces COX-2 mRNA expression through P38MAPK and CREB independent of small GTPases in intestinal epithelial cells.Biochimica et Biophysica Acta 1745(2005)393-400
[17]lecomet M,Laneuville Q,Ji C,et al.Acetylation of human prostagland in-endoperoxid synthase-2 by aspirin.J Biol them,1994,269:13207
[18]Kazuhito Tatsu,et al.Cyclooxygenase-2 in sporiadic colorectal polyps:Immunohistochemical study and its importance in the early stsges of colorectal tumorigenesis.Pathology-Research and Practice,201(2005)427-433
[19]Masferrer Jh,leahy KM,Koki AT,et al.Antiangiogenic and antitumor activities of eyclooxygenase-2 inhibitors[J].Can Res,2000,60(5):1306-1311
[20]You-Cheng Hseu,et al.Anti-inflammatory potential of Antrodia Camphorata through inhibition of iNOS,COX-2 and cytokines via the NF-κB pathway.Intemational Immunopharmacology 5(2005)1914-1925
[21]Mark A.Hull.Cyclooxygenase-2:How good is it as a target for cancer chemoprevention? European Journal of Cancer 41(2005)1854-1863
[22]T HIa,K Neilson.Human cyclooxygenase-2 cDNA.Proc Natl Acad Sci USA,1992,89:7384-7388
[23]Wei Liu,Steven Dubinett,Simie Lavern A.Patterson,Kathleen A.Kelly.COX-2inhibition affects growth rate of Chlamydia muridarum within epithelial cells.Microbes and Infection(2005)2626-2635
[24]Lucrecia Ma'rquez-Rosado,et al.Celecoxib,a cyclooxygenase-2 inhibitor,prevents induction of liver preneoplastic lesions in rats.Journal of Hepatology 43(2005)653-660
[25]Andreas D.Ebert,Julia Bartley,Matthias David.Aromatase inhibitors and cyclooxygenase-2(COX-2)inhibitors in endometriosis:New questions—old answers?European Journal of Obstetrics & Gynecology and Reproductive Biology 122(2005)144-150
[26]Langenbach R,Loftin Ch.Cyclooxygenase knockout mice models for elucidating isoform-specific functions.Biochem Pharmacol,1999,58(8):1237-1246
[27]Ridley SH,Sarsfieid SJ,Lee Je,et al.Actions of IL-1 are selectively controlled by P38 mitogen-actived protein kinase.J Immunol,1997,158:3165
[28]Jen-Hao Chen,et al.Effects of COX-2 inhibitor on growth of human gastric cancer cells and its relation to hepatocyte growth factor.Cancer Letters 12(2005)1-8
[29]Mei-Hua Li,Jung-Hee Jang,Young-Joon Surh.Nitric oxide induces apoptosis via AP-1 driven upregulation of COX-2 in rat pheochromocytoma cells.Free Radical Biology &Medicine 39(2005)890-899
[30]Vattoly J.Majo,et al.A general method for the synthesis of aryl[11C]methylsulfones:Potential PET probes for imaging cyclooxygenase-2expression.Bioorg.Med.Chem.Lett,15(2005)4268-4271
[31]Guang-Zhi Yang,Li Li,Hua-Ye Ding,Jin-Song Zhou.Cyclooxygenase-2 is over-expressed in Chinese esophageal squamous cell carcinoma,and correlated with NF-κB:An immunohistochemical study.Expreimetal and Moleculal Pathlogy 79(2005)214-218
[32]蒋代华,郭德玉,刘友生等.环氧化酶-2在肿瘤研究中的应用进展.临床医药杂志,2004:17(1)32-34
[33]Gallo O,Masini E,Bianchi B,et al.Hum Pathol,2002,33(7):708-714
[34]Tan KB,Putti TC.Cyclooxygenase-2 expression in nasopharyngeal carcinoma:immunohistochemical findings and potential implications.J ClAn Pathol,2005,58(5):545-538
[35]Soo R,Putti T,Tao Q,et al.Overexpression of cyclooxygenase-2 in nasopharyngeal carcinoma and associstion with epidermal growth factor receptor expression.Arch Otolaryngol Head Neck Surg,2005,131(2):147-152
[36]Nathan CA,Leskov IL,Lin N,et al.CoX-2 expression in dysplasia of the head and neck correlation with eIF4e.Cancer,2001,9(7):1888-1895
[37]Chen WC,McBride WH,Chen SM,et al.Prediction of poor survival by cyclooxygenase-2in patients with T_4 nasopharyngeal cancer treated by radiation therapy:clinical and in vitro studies.Head Neck,2005,27(6):503-512
[38]马长春、李德锐等.EB病毒潜伏膜蛋白1的基础研究进展与临床意义.汕头大学医学院学报,2004.17:62-64
[39]胡利福.EBV标码的潜伏膜蛋白.癌症,2002,21:559-566
[40]李智,宗永生.鼻咽癌组织中潜伏膜蛋白1的表达对癌细胞增殖和凋亡的影响.中华病理学杂志,1999,28(5):340-343.
[41]Murono S,Yoshizaki T,Park CS.Association of Epstein-Barr vitus infection with p53 protein accumulation but not bcl-2 protein in nasopharngeat carcinoma.Histopathology,1999,34(5):432-438.
[42]Eliopoulos AG,Waites ER,Blake SM,et al.TRAF1 is a critical regulator of JNK signaling by the TRAF-binding domain of the Epstein-Barr virus-encoded latent infection membrance protein 1 but not CD40.J Viros,2003,77(2):1316-1328.
[43]Godd JD,Salisbury JR,Packham G,et al.A20 RNA expression is associated with undeferentiated nasopharygeal carcinoma and poorly differentiated head and neck squamous cell carcinoma.J Pathol,1999,187(5):549-555.
[44]王承兴,邓锡云,李小艳,等.EB病毒LMP1在鼻咽癌绌胞系中通过NF-κB、AP-1促进MMP9表达.中华肿瘤杂志,2002,24(1):9-13.
[45]Yoshizaki T.Promotion of metastasis in nasopharngeal carcinoma by Epstein-Barr vitus latent membrane protein-1.Histol Histopathol,2002,17(3):845-850.
[46]蔡朝阳,汤建国,李旋,等.基质金属蛋白酶-9和IL8在鼻咽癌中的表达及其与潜伏膜蛋白1的相关性研究.临床耳鼻咽喉头颈外科杂志,2007,21(21):966-969.
[47]Murono S,Inone H,Tanabe T,et al.Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor in nasopharyngeal carcinoma cell.Proc Natl Acad Sci LSA,2001,98(12):6905-6910.
[48]Aeckel EC,Naja S,Tan J,et al.Correlation of expression of cyclooxygenase-2,Vasular endothelial growth factor,and peroxisome proliferator-activated receptor delta with head and neck squamous cell carcinoma.Arch Otolaryngol Head Neck Surg,2001,127(10):1253-1259.
[1]Yoshimura R, Sano H, Masuda C, et al. Expression of cyclooxygenase-2 in prostate carcinoma [J]. Cancer, 2000, 89(3): 589-596
[2]Williams CS, et al. Prostaglandin endoperoxide synthese: Why two isoforms? Am J Physiol, 1996, 270(3 Pt 1): G393-400
[3]Lindsay M. Shafer, Lee W. Slice. Anisomycin induces COX-2 mRNA expression through P38MAPK and CREB independent of small GTPases in intestinal epithelial cells. Biochimica et Biophysica Acta 1745(2005)393-400
[4]lecomet M, Laneuville Q, Ji C, et al. Acetylation of human prostagland in-endoperoxid synthase-2 by aspirin. J Biol Chem, 1994, 269: 13207
[5]Kazuhito Tatsu, et al. Cyclooxygenase-2 in sporiadic colorectal polyps: Immunohistochemical study and its importance in the early stsges of colorectal tumorigenesis. Pathology-Research and Practice, 201(2005)427-433
[6]Masferrer JL, leahy KM, Koki AT, et al. Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors [J]. Can Res, 2000, 60(5): 1306-1311
[7]You-Cheng Hseu, et al. Anti-inflammatory potential of Antrodia Camphorata through inhibition of iNOS, COX-2 and cytokines via the NF-κB pathway. International Immunopharmacology 5 (2005) 1914-1925
[8]Mark A. Hull. Cyclooxygenase-2: How good is it as a target for cancer chemoprevention? European Journal of Cancer 41 (2005) 1854 - 1863
[9]T HIa, K Neilson. Human cyclooxygenase-2 cDNA. Proc Natl Acad Sci USA, 1992, 89: 7384-7388
[10]Vezza R, Habib A, Li H, et al. Regulation of cyclooxygenases by protein Kinase C. Evidence against the importance of direct enzyme phosphorylation. J Biol Chem, 1996, 271: 30028-30033
[11]MillerC, Zhang M, He Y, et al. Transcriptional induction of cyclooxygenase-2 gene by okadaic acid inhibition of Phosphatase activity in human chondrocytes: Co-stimulation of AP-1 and CRE nuclear binding proteins. J Cell Biochen, 1998, 69(4): 392-413
[12]M Gophelt-Struebe, A Huhn, M Stroebel, et al. Independent regulation of cyclooxygenase-2 expression by p42/44 mitogen-activated protein kinases and Ca2+/calmodulin-dependent kinase. Biochem J, 1999, 339: 329-334
[13]WW Lin, B Chen. Induction of cyclooxyenase-2 expression by nethyl arachidonyl fluorophosphonate in murine J774 macrophages: roles of protein kinase C, ERKs and p38 MAPK. Br J Pharmacol, 1999, 126: 1419-1425
[14]Sheng HM, Shao TY, Dubois RN. K-Ras-mediated increase in cyclooxygenase-2 mRNA stability involves activation of the protein Kinase B. Cancer Res, 2001, 61(6): 2670-2675
[15]Wei Liu, Steven Dubinett, Simie Lavern A. Patterson, Kathleen A. Kelly . COX-2 inhibition affects growth rate of Chlamydia muridarum within epithelial cells. Microbes and Infection (2005) 2626-2635
[16]Lucrecia Ma'rquez-Rosado, et al. Celecoxib, a cyclooxygenase-2 inhibitor, prevents induction of liver preneoplastic lesions in rats. Journal of Hepatology 43 (2005) 653 - 660
[17]Andreas D. Ebert, Julia Bartley, Matthias David. Aromatase inhibitors and cyclooxygenase-2 (COX-2) inhibitors in endometriosis: New questions-old answers? European Journal of Obstetrics & Gynecology and Reproductive Biology 122 (2005) 144-150
[18]Langenbach R,Loftin Ch.Cyclooxygenase knockout mice models for elucidating isoform-specific functions.Biochem Pharmacol,1999,58(8):1237-1246
[19]Ridley SH,Sarsfieid SJ,Lee Je,et al.Actions of IL-1 are selectively controlled by P38 mitogen-actived protein kinase.J Immunol,1997,158:3165
[20]Jen-Hao Chen,et al.Effects of COX-2 inhibitor on growth of human gastric cancer cells and its relation to hepatocyte growth factor.Cancer Letter 12(2005)1-8
[21]Mei-Hua Li,Jung-Hee JanE,Young-Joon Surh.Nitric oxide induces apoptosis via AP-1 driven upregulation of COX-2 in rat pheochromocytoma cells.Free Radical Biology & Medicine 39(2005)890-899
[22]Vattoly J.Majo,et al.A general method for the synthesis of ary[11C]methylsulfones:Potential PET probes for imaging cyclooxygenase-2 expression.Bioorg.Med.Chem.Lett.15(2005)4268-4271
[23]Olaf Buchweitz,Annette Staebler,Pia Wu ifing,Erik Hauzman,Robert Greb,Ludwig Kiesel.COX-2 overexpression in peritoneal lesions is correlated with nonmenstrual chronic pelvic pain.European Journal of Obstetrics & Gynecology and Reproductive Biology(2005)121-125
[24]Guang-Zhi Yang,Li Li,Hua-Ye Ding,Jin-Song Zhou.Cyclooxygenase-2 is over-expressed in Chinese esophageal squamous cell carcinoma,and correlated with NF-κB:An immunohistochemical study,Expreimetal and Moleculal Pathlogy 79(2005)214-218
[25]Mitchell JA,Akarasereen out P,Thiemermann C,et al.Selectivity of nonsteroidal anti-inflammatony drugs as inhibitors of constitutive and inducible cyclooxygenase[J].Proc Natl Acad Sci USA,1994,90:11693
[26]Engelhardt G,Bogel R,Schnitzer C,et al.Meloxican influence on arachidonic acid metabolism in vitro findings[J].Biochem Pharmacol,1996,51:21
[27]Tsujii M.COX-2 expression in humun colon cancer increases metastatic peotential.Proc Natl Acid Sci USA,1997,94:3336-3340
[28]J.Rubioa,D.Ramos,J.A.Lo'pez-Guerrero,I.Iborra,A.Colladoa,E.Solsona,S.Almenar,A.Llombart-Bosch.Immunohistochemical Expression of Ki-67 Antigen,COX-2and Bax/Bcl-2 in Prostate Cancer.Prognostic value in Biopsies and Radical Prostatectomy Specimens.European Urology 48(2005)745- 751
[29]Helen,H.W,Chert M.D,et al.Incresed expression of nitric oxide synthase and cyclooxygenase-2 is associated with poor survival in cancer treated with radiotherapy,doi:10.1016/j,ijrobp.2005.03.062
[30]Zoshihisa Ohta,Mami Takahashi,Atsushi Ochiai.Increased protein expression of both inducible nitric oxide synthase and cyclooxygenase-2 in human colon cancers.Cancer Letters(2005)1-8
[31]Induction of Angiopoietin-2 gene expression by COX-2:A novel role for COX-2inhibitors during hepatocarcinogenesis.Journal of Hepatology(2005)1-2
[32]Jyh-Ping Peng,Hui-Chiu Chang,Chung-Feng Hwang,Wen-Chun Hung.Overexpression of cyclooxygenase-2 in nasopharyngeal carcinoma and association with lymph node metastasis.Oral Oncology(2005)41,903-908
[33]Tucker,O.N.,Dannenberg,A.J.,Yang,E.K.et al.Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer.Cancer Res,59:987,1999
[34]Elder,D.J.,Halton,D.E.,Playle,L.C.et al.The MEK/ERK pathway mediates COX-2-selective NSAID-induced apoptosis and induced COX-2 protein expression in colorectal carcinoma cells. Int J Cancer, 99: 323, 2002
[35]Eibl, G., Reber, H. A., Wente, M. N. et al. The selective cyclooxygenase-2 inhibitor nimesulide induces apoptosis in pancreatic cancer cells independent of COX-2. Pancreas, 26: 33, 2003
[36]Tardieu, D., Jaeg, J. P., Deloly, A. et al. The COX-2 inhibitor nimesulide suppresses superoxide and 8-hydroxy-deoxyguanosine formation, and stimulates poptosis in mucosa during early colonic inflammation in rats. Carcinogenesis, 21: 937, 2000
[37]Yao, R., Rioux, N., Castonguay, A. et al. Inhibition of COX-2 and induction of apoptosis: two determinants of nonsteroidal anti-inflammatory drugs' chemopreventive efficacies in mouse lung tumorigenesis. Exp Lung Res, 26:731, 2000
[38]Li, M., Wu, X., Xu, X. C. Induction of apoptosis in colon cancer by cyclooxygenase-2 inhibitor NS398 through a cytochrome c-dependent pathway. Clin Cancer Res, 7: 1010, 2001
[39]Li, M., Wu, X., Xu, X. C. Induction of apoptosis by cyclooxygenase-2 inhibitor NS398 through a cytochrome C-dependent pathway in esophageal cancer cells. Int J Cancer, 93: 218, 2001
[40]Tsujii M, et al. Alterations in cellular adhesion and apoptosis inepithelial cells over expressing prostaglandin endospreroxide synthase 2. Cell, 1995, 83: 493-501
[41]Sheng H. Modulation of apoptosis and bcl-2 expression by prostaglantin E_2 in human colon cancer cells. Cancer Res, 1998, 58: 326-336
[42] Jones MK, Wang H, Peskar BM Levin E, Itani RM, sarfdh IJ, Tarnawski AS Inhibition of angiogenesis by nonsteroidal anti-in-flammatory drugs: insight into mechanisms and implications for cancer growth and ulcer healing. Nat Med, 1995, 5: 1418-1423
[43]Gilhooly EM, Rose DP. The association between a mutated ras gene and cyclooxygenase-2 expression in human breast cancer cell lines. 1999,15:267-270
[44]Chan G, Boyle Jo, Yang EK, et al. Mechanisms underlying nonseroidal anti-inflammatory grug-mediated apoptosis. Cancer Res, 1999, 59(5): 991-994
[45]Castonguay A, Rioux N. Inhibition of Lung tumorigenesis by sulindac: comparison of two experimental protocols. 1997, Carcinogenesis 18: 491-496
[46]Lin XH, Yao S, Kirschenbaum A, Levine AC. NS398, a selective cyclooxygenase-2 inhibitor, induces apoptosis, and down-regulates bcl-2 expression in LNCap cells. Cancer Res, 1998, 58: 4245-4249
[47]Tsujii M, kawano S, DuBosi RN. Cyclooxygenase-2 expression in human colon cancer cells increases metastasic potential. Proc Natl Acad Sci USA, 1997, 94: 3336— 3340
[48]Koga H, Sakisaka S, Ohishi M, et al. Expression of COX-2 in human hepatocellular carinoma:releance to tumor dedifferentiation [J]. Hepatolony, 1999, 29(3): 688-696
[49]Stolina M, et al. Specific inhibition of IL-10 and IL-12 synthesis. J Immunol, 2000, 164: 361-370
[50]Kambayashi T. Potential involvement of IL-10 in suppression tumor associated macrophages colon-26-derived PGE_2 inhibits TNP-α release via a mechanism involving IL-10. J Immunol, 154: 3383-3390
[51]Tsutomu, et al. Relation between COX-2 expression and tumor invasiveness and patient survival in transitional cell carcinoma of the urinany bladder. 2001, 92: 188-193
[52]Prescott SM. Intimate connections between APC and prostaglandin H synthase-2 . Cell, 1996,87:783-786
[53]Attiga FA,et al.Effect of the cyclooxygenase-2(COX-2)-selective inhibitor NS398on the secretion of matrix metalloproteinases(MMP-2 and MMP-9)and tissue inhibitors of metalloproteinases(TIMP-1 and TIMP-2)from human prostate tumor cells.Peoc AM Assco Cancer Res,41:131-132
[54]蒋代华,郭德玉,刘友生等.环氧化酶-2在肿瘤研究中的应用进展.临床医药杂志,2004,17(1)32-34.
[55]Gallo O,Masini E,Bianchi B,et al.Hum Pathol,2002,33(7):708-714
[56]Tan KB,Putti TC.Cyclooxygenase-2 expression in nasopharyngeal carcinoma:immunohistochemical findings and potential implications.J ClAn Pathol,2005,58(5):545-538.
[57]Steinbach G,Lynch PM,Philips RK,et al.The effect of celecoxib,a cyclooxegenase-2inhibitor,in familial adenomatous polyposis[J].N Engl J Med,2000,342(26):1946-1952.
[58]Lanza-Jacoby S,Miller S,Flynn J,Gallatig K,et al.The Cyclooxygenase-2 Inhibitor,Celecoxib,Prevents the Development of Mammary Tumors in HER-2/neu Mice[J].Cancer Epidemiol Biomarkers Prey,2003 Dec 1,12(12):1486-1491
[59]Soo R,Putti T,Tao Q,et al.Over expression of cyclooxygenase-2 in nasopharyngeal carcinoma and association with epidermal growth factor receptor expression.Arch Otolaryngol Head Neck Surg,2005,131(2):147-152
[60]Nathan CA,Leskov IL,Lin N,et al.COX-2 expression in dysplasia of the head and neck correlation with eIF4e.Cancer,2001,9(7):1888-1895
[61]Chen WC,McBride WH,then SM,et al.Prediction of poor survival by cyclooxygenase-2in patients with T_4 nasopharyngeal carcer treated by radiation therapy:clinical and in vitro studies.Head Neck,2005,27(6):503-512
[62]邓刚,杨成章,陈望燕.环氧化酶-2与Ki-67在喉鳞状细胞癌中表达的特点及其临床意义.中国现代医学杂志,2005,15(17):2632-2635
[63]Masunaga R,Klhno H,et al.Cyclooxygenase-2 expression correlates with tumor neovacularization and prognosis in human colorectal carcinoma patients[J].Clin Cancer Res,2002,6(10):4064-4068
[64]马长春,李德锐等.EB病毒潜伏膜蛋白l的基础研究进展与临床意义.汕头大学医学院学报,2004,1(17),62-64
[65]胡利福.EBV标码的潜伏膜蛋白[J].癌症,2002,21(5):559-566.
[66]Teramoto N,Maeda A,Kobayashi K,et al.Epstein-Barr vitus infection to Epstein-Barr vitus-negative nasooharyngeal carcinoma cell line TWO_3 enhances its tumorigenicity.Lab Invest,2000,80(3):303-312
[67]李智,宗永生.鼻咽癌组织中潜伏膜蛋白1的表达对癌细胞增殖和凋亡的影响.中华病理学杂志,1999,28(5):340-343
[68]王承兴,邓锡云,李小艳,等.EB病毒LMP1在鼻咽癌细胞系中通过NF-κB、AP-1促进MMP9表达.中华肿瘤杂志,2002,24(1):9-13
[69]Yoshizaki T.Promotion of metastasis in nasopharngeal carcinoma by Epstein-Barr virus latent membrane protein-1.Histol Histopathol,2002,17(3):845-50
[70]Murono S,Inone H,Tanabe T,et al.Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor in nasopharyngeal carcinoma cell.Proc Natl Acad Sci LSA,2001,98(12):6905-6910
[71]Aeckel EC,Raja S,Tan J,et al.Correlation of expression of cyclooxygenase-2,Vasular endothelial growth factor,and peroxisome proliferator-activated receptor delta with head and neck squamous cell carcinoma.Arch Otolaryngol Head Neck Surg,2001,127(10):1253-1259