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[Cancer Research 59, 198-204, January 1, 1999]
© 1999 American Association for Cancer Research

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[Cancer Research 59, 198-204, January 1, 1999]
© 1999 American Association for Cancer Research


Tumor Biology

Cyclooxygenase-2 Expression in Human Esophageal Carcinoma1

Katja C. Zimmermann, Mario Sarbia2, Artur-Aron Weber, Franz Borchard, Helmut E. Gabbert and Karsten Schrör

Institut für Pharmakologie [K. C. Z., A-A. W., K. S.] and Institut für Pathologie [M. S., H. E. G.], Heinrich-Heine-Universität, 40225 Düsseldorf, and Institut für Pathologie, Klinikum Aschaffenburg, 63739 Aschaffenburg [F. B.], Germany

On the basis of epidemiological observations that nonsteroidal anti-inflammatory drugs reduce the risk of esophageal carcinoma, we studied the expression of cyclooxygenase-2 (COX-2) in esophageal squamous cell carcinomas (SCCs; n = 172) and in esophageal adenocarcinomas (ADCs; n = 27). Using immunohistochemistry, we observed COX-2 expression in 91% of the SCCs and in 78% of the ADCs. Western blot analysis showed enhanced expression of the COX-2 protein in some tumors as compared with normal esophageal squamous epithelium, whereas similar amounts of the COX-1 protein were found in normal and cancerous tissues. COX expression was also studied in two esophageal cancer cell lines (OSC-1 and OSC-2) to evaluate the functional relevance of COX-2-derived prostaglandins (PGs). OSC-2 cells expressed COX-2 but not COX-1, whereas OSC-1 cells expressed high levels of COX-1 but showed only a very weak COX-2 expression. Accordingly, PGE2 synthesis was 600 times higher in the OSC-2 cells as compared with the OSC-1 cells. Treatment of OSC-2 cells with the selective COX-2 inhibitors flosulide and NS-398 concentration dependently suppressed PGE2 synthesis and proliferation and also induced apoptosis. In contrast, no effect of the COX-2 inhibitors was seen in OSC-1 cells. Our data demonstrate that COX-2 is expressed in the majority of esophageal SCCs and ADCs and that COX-2-derived PGs play an important role in the regulation of proliferation and apoptosis of esophageal tumor cells. It is concluded that inhibition of COX-2 may be useful in the therapy of esophageal cancer.




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Carcinogenesis, February 1, 2002; 23(2): 245 - 256.
[Abstract] [Full Text] [PDF]


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J. Pharmacol. Exp. Ther.Home page
E. Fritsche, S. J. Baek, L. M. King, D. C. Zeldin, T. E. Eling, and D. A. Bell
Functional Characterization of Cyclooxygenase-2 Polymorphisms
J. Pharmacol. Exp. Ther., November 1, 2001; 299(2): 468 - 476.
[Abstract] [Full Text] [PDF]


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CarcinogenesisHome page
G. D. Stoner and A. Gupta
Etiology and chemoprevention of esophageal squamous cell carcinoma
Carcinogenesis, November 1, 2001; 22(11): 1737 - 1746.
[Abstract] [Full Text] [PDF]


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Clin. Cancer Res.Home page
K. Saukkonen, O. Nieminen, B. van Rees, S. Vilkki, M. Harkonen, M. Juhola, J.-P. Mecklin, P. Sipponen, and A. Ristimaki
Expression of Cyclooxygenase-2 in Dysplasia of the Stomach and in Intestinal-type Gastric Adenocarcinoma
Clin. Cancer Res., July 1, 2001; 7(7): 1923 - 1931.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
T. Shono, P. J. Tofilon, J. M. Bruner, O. Owolabi, and F. F. Lang
Cyclooxygenase-2 Expression in Human Gliomas: Prognostic Significance and Molecular Correlations
Cancer Res., June 1, 2001; 61(11): 4375 - 4381.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
S. Murono, H. Inoue, T. Tanabe, I. Joab, T. Yoshizaki, M. Furukawa, and J. S. Pagano
Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor production in nasopharyngeal carcinoma cells
PNAS, May 24, 2001; (2001) 121016998.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
K. J. Sales, A. A. Katz, M. Davis, S. Hinz, R. P. Soeters, M. D. Hofmeyr, R. P. Millar, and H. N. Jabbour
Cyclooxygenase-2 Expression and Prostaglandin E2 Synthesis Are Up-Regulated in Carcinomas of the Cervix: A Possible Autocrine/Paracrine Regulation of Neoplastic Cell Function via EP2/EP4 Receptors
J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2243 - 2249.
[Abstract] [Full Text]


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CarcinogenesisHome page
Z. Li, Y. Shimada, A. Kawabe, F. Sato, M. Maeda, I. Komoto, T. Hong, Y. Ding, J. Kaganoi, and M. Imamura
Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in F344 rats by JTE-522, a selective COX-2 inhibitor
Carcinogenesis, April 1, 2001; 22(4): 547 - 551.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
F. Biramijamal, A. Allameh, P. Mirbod, H.-J. Groene, R. Koomagi, and M. Hollstein
Unusual Profile and High Prevalence of p53 Mutations in Esophageal Squamous Cell Carcinomas from Northern Iran
Cancer Res., April 1, 2001; 61(7): 3119 - 3123.
[Abstract] [Full Text]


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Cancer Res.Home page
C. A. Eads, R. V. Lord, K. Wickramasinghe, T. I. Long, S. K. Kurumboor, L. Bernstein, J. H. Peters, S. R. DeMeester, T. R. DeMeester, K. A. Skinner, et al.
Epigenetic Patterns in the Progression of Esophageal Adenocarcinoma
Cancer Res., April 1, 2001; 61(8): 3410 - 3418.
[Abstract] [Full Text]


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Clin. Cancer Res.Home page
M. Li, X. Wu, and X.-C. Xu
Induction of Apoptosis in Colon Cancer Cells by Cyclooxygenase-2 Inhibitor NS398 through a Cytochrome c-dependent Pathway
Clin. Cancer Res., April 1, 2001; 7(4): 1010 - 1016.
[Abstract] [Full Text]


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GutHome page
S Chariyalertsak, V Sirikulchayanonta, D Mayer, A Kopp-Schneider, G Furstenberger, F Marks, and K Muller-Decker
Aberrant cyclooxygenase isozyme expression in human intrahepatic cholangiocarcinoma
Gut, January 1, 2001; 48(1): 80 - 86.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
R. F. Souza, K. Shewmake, D. G. Beer, B. Cryer, and S. J. Spechler
Selective Inhibition of Cyclooxygenase-2 Suppresses Growth and Induces Apoptosis in Human Esophageal Adenocarcinoma Cells
Cancer Res., October 1, 2000; 60(20): 5767 - 5772.
[Abstract] [Full Text]


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Clin. Cancer Res.Home page
R. Masunaga, H. Kohno, D. K. Dhar, S. Ohno, M. Shibakita, S. Kinugasa, H. Yoshimura, M. Tachibana, H. Kubota, and N. Nagasue
Cyclooxygenase-2 Expression Correlates with Tumor Neovascularization and Prognosis in Human Colorectal Carcinoma Patients
Clin. Cancer Res., October 1, 2000; 6(10): 4064 - 4068.
[Abstract] [Full Text]


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J. Clin. Endocrinol. Metab.Home page
A. Kirschenbaum, D. R. Liotta, S. Yao, X.-H. Liu, A. P. Klausner, P. Unger, E. Shapiro, I. Leav, and A. C. Levine
Immunohistochemical Localization of Cyclooxygenase-1 and Cyclooxygenase-2 in the Human Fetal and Adult Male Reproductive Tracts
J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3436 - 3441.
[Abstract] [Full Text]


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Cancer Res.Home page
T. Joki, O. Heese, D. C. Nikas, L. Bello, J. Zhang, S.-K. Kraeft, N. T. Seyfried, T. Abe, L. B. Chen, R. S. Carroll, et al.
Expression of Cyclooxygenase 2 (COX-2) in Human Glioma and in Vitro Inhibition by a Specific COX-2 Inhibitor, NS-398
Cancer Res., September 1, 2000; 60(17): 4926 - 4931.
[Abstract] [Full Text]


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Am. J. Pathol.Home page
J. J. Y. Sung, W. K. Leung, M. Y. Y. Go, K. F. To, A. S. L. Cheng, E. K. W. Ng, and F. K. L. Chan
Cyclooxygenase-2 Expression in Helicobacter pylori-Associated Premalignant and Malignant Gastric Lesions
Am. J. Pathol., September 1, 2000; 157(3): 729 - 735.
[Abstract] [Full Text] [PDF]


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CarcinogenesisHome page
M. Takahashi, M. Mutoh, T. Kawamori, T. Sugimura, and K. Wakabayashi
Altered expression of {beta}-catenin, inducible nitric oxide synthase and cyclooxygenase-2 in azoxymethane-induced rat colon carcinogenesis
Carcinogenesis, July 1, 2000; 21(7): 1319 - 1327.
[Abstract] [Full Text] [PDF]


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Cancer Epidemiol. Biomarkers Prev.Home page
M. Li, R. Lotan, B. Levin, E. Tahara, S. M. Lippman, and X.-C. Xu
Aspirin Induction of Apoptosis in Esophageal Cancer: A Potential for Chemoprevention
Cancer Epidemiol. Biomarkers Prev., June 1, 2000; 9(6): 545 - 549.
[Abstract] [Full Text]


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J. Biol. Chem.Home page
A.-L. Hsu, T.-T. Ching, D.-S. Wang, X. Song, V. M. Rangnekar, and C.-S. Chen
The Cyclooxygenase-2 Inhibitor Celecoxib Induces Apoptosis by Blocking Akt Activation in Human Prostate Cancer Cells Independently of Bcl-2
J. Biol. Chem., April 6, 2000; 275(15): 11397 - 11403.
[Abstract] [Full Text] [PDF]


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CarcinogenesisHome page
A. K. Bauer, L. D. Dwyer-Nield, and A. M. Malkinson
High cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) contents in mouse lung tumors
Carcinogenesis, April 1, 2000; 21(4): 543 - 550.
[Abstract] [Full Text] [PDF]


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Clin. Cancer Res.Home page
A. Shamma, H. Yamamoto, Y. Doki, J. Okami, M. Kondo, Y. Fujiwara, M. Yano, M. Inoue, N. Matsuura, H. Shiozaki, et al.
Up-Regulation of Cyclooxygenase-2 in Squamous Carcinogenesis of the Esophagus
Clin. Cancer Res., April 1, 2000; 6(4): 1229 - 1238.
[Abstract] [Full Text]


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CarcinogenesisHome page
M. T. Yip-Schneider, D. S. Barnard, S. D. Billings, L. Cheng, D. K. Heilman, A. Lin, S. J. Marshall, P. L. Crowell, M. S. Marshall, and C. J. Sweeney
Cyclooxygenase-2 expression in human pancreatic adenocarcinomas
Carcinogenesis, February 1, 2000; 21(2): 139 - 146.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
C.-J. Yuan, A. K. Mandal, Z. Zhang, and A. B. Mukherjee
Transcriptional Regulation of Cyclooxygenase-2 Gene Expression: Novel Effects of Nonsteroidal Anti-Inflammatory Drugs
Cancer Res., February 1, 2000; 60(4): 1084 - 1091.
[Abstract] [Full Text]


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Clin. Cancer Res.Home page
H. Y. Lim, H. J. Joo, J. H. Choi, J. W. Yi, M. S. Yang, D. Y. Cho, H. S. Kim, D. K. Nam, K. B. Lee, and H. C. Kim
Increased Expression of Cyclooxygenase-2 Protein in Human Gastric Carcinoma
Clin. Cancer Res., February 1, 2000; 6(2): 519 - 525.
[Abstract] [Full Text]


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Clin. Cancer Res.Home page
M. Kondo, H. Yamamoto, H. Nagano, J. Okami, Y. Ito, J. Shimizu, H. Eguchi, A. Miyamoto, K. Dono, K. Umeshita, et al.
Increased Expression of COX-2 in Nontumor Liver Tissue Is Associated with Shorter Disease-free Survival in Patients with Hepatocellular Carcinoma
Clin. Cancer Res., December 1, 1999; 5(12): 4005 - 4012.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
S. I. Mohammed, D. W. Knapp, D. G. Bostwick, R. S. Foster, K. N. M. Khan, J. L. Masferrer, B. M. Woerner, P. W. Snyder, and A. T. Koki
Expression of Cyclooxygenase-2 (COX-2) in Human Invasive Transitional Cell Carcinoma (TCC) of the Urinary Bladder
Cancer Res., November 1, 1999; 59(22): 5647 - 5650.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
M. A. Molina, M. Sitja-Arnau, M. G. Lemoine, M. L. Frazier, and F. A. Sinicrope
Increased Cyclooxygenase-2 Expression in Human Pancreatic Carcinomas and Cell Lines: Growth Inhibition by Nonsteroidal Anti-Inflammatory Drugs
Cancer Res., September 1, 1999; 59(17): 4356 - 4362.
[Abstract] [Full Text] [PDF]


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Clin. Cancer Res.Home page
J. Okami, H. Yamamoto, Y. Fujiwara, M. Tsujie, M. Kondo, S. Noura, S. Oshima, H. Nagano, K. Dono, K. Umeshita, et al.
Overexpression of Cyclooxygenase-2 in Carcinoma of the Pancreas
Clin. Cancer Res., August 1, 1999; 5(8): 2018 - 2024.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
L. Du Plessis, E. Dietzsch, M. Van Gele, N. Van Roy, P. Van Helden, M. I. Parker, D. K. Mugwanya, M. De Groot, M. P. Marx, M. J. Kotze, et al.
Mapping of Novel Regions of DNA Gain and Loss by Comparative Genomic Hybridization in Esophageal Carcinoma in the Black and Colored Populations of South Africa
Cancer Res., April 1, 1999; 59(8): 1877 - 1883.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
M.-T. Lin, R.-C. Lee, P.-C. Yang, F.-M. Ho, and M.-L. Kuo
Cyclooxygenase-2 Inducing Mcl-1-dependent Survival Mechanism in Human Lung Adenocarcinoma CL1.0 Cells. INVOLVEMENT OF PHOSPHATIDYLINOSITOL 3-KINASE/Akt PATHWAY
J. Biol. Chem., December 21, 2001; 276(52): 48997 - 49002.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
S. Murono, H. Inoue, T. Tanabe, I. Joab, T. Yoshizaki, M. Furukawa, and J. S. Pagano
Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor production in nasopharyngeal carcinoma cells
PNAS, June 5, 2001; 98(12): 6905 - 6910.
[Abstract] [Full Text] [PDF]




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