Cyclooxygenase-2 Expression Is Up-Regulated in Human Pancreatic Cancer

EMT and Cancer Progression and Treatment

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Cyclooxygenase-2 Expression Is Up-Regulated in Human Pancreatic Cancer¹

Olga N. Tucker, Andrew J. Dannenberg, Eun K. Yang, Fan Zhang, Lisong Teng, John M. Daly, Robert A. Soslow, Jaime L. Masferrer, Bryan M. Woerner, Alane T. Koki and Thomas J. Fahey, III²

Departments of Surgery [O. N. T., A. J. D., L. T., J. M. D., T. J. F.], Medicine [A. J. D., E. K. Y.], and Pathology [R. A. S.], New York Presbyterian Hospital and Weill Medical College of Cornell University, and Strang Cancer Prevention Center [A. J. D., F. Z., T. J. F.], New York, New York 10021; and Searle Discovery Research, Monsanto Company, St. Louis, Missouri 63017 [J. L. M., B. M. W., A. T. K.]

A large body of evidence suggests that cyclooxygenase-2 (COX-2)is important in gastrointestinal cancer. The purpose of thisstudy was to determine whether COX-2 was expressed in adenocarcinomaof the human pancreas. Quantitative reverse transcription-PCR,immunoblotting, and immunohistochemistry were used to assessthe expression of COX-2 in pancreatic tissue. Levels of COX-2mRNA were increased by >60-fold in pancreatic cancer comparedto adjacent nontumorous tissue. COX-2 protein was present in9 of 10 cases of adenocarcinoma of the pancreas but was undetectablein nontumorous pancreatic tissue. Immunohistochemical analysisshowed that COX-2 was expressed in malignant epithelial cells.In cultured human pancreatic cancer cells, levels of COX-2 mRNAand protein were induced by treatment with tumor-promoting phorbolesters. Taken together, these results suggest that COX-2 maybe a target for the prevention or treatment of pancreatic cancer.

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Clin. Cancer Res., November 1, 2001; 7(11): 3349 - 3355.
[Abstract] [Full Text] [PDF]

A. H. Klimp, H. Hollema, C. Kempinga, A. G. J. van der Zee, E. G. E. de Vries, and T. Daemen
Expression of Cyclooxygenase-2 and Inducible Nitric Oxide Synthase in Human Ovarian Tumors and Tumor-associated Macrophages
Cancer Res., October 1, 2001; 61(19): 7305 - 7309.
[Abstract] [Full Text] [PDF]

H. Pyo, H. Choy, G. P. Amorino, J.-s. Kim, Q. Cao, S. K. Hercules, and R. N. DuBois
A Selective Cyclooxygenase-2 Inhibitor, NS-398, Enhances the Effect of Radiation in Vitro and in Vivo Preferentially on the Cells That Express Cyclooxygenase-2
Clin. Cancer Res., October 1, 2001; 7(10): 2998 - 3005.
[Abstract] [Full Text] [PDF]

M. T. Yip-Schneider, C. J. Sweeney, S.-H. Jung, P. L. Crowell, and M. S. Marshall
Cell Cycle Effects of Nonsteroidal Anti-Inflammatory Drugs and Enhanced Growth Inhibition in Combination with Gemcitabine in Pancreatic Carcinoma Cells
J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 976 - 985.
[Abstract] [Full Text]

E. M. P. de Almeida, C. Piche, J. Sirois, and M. Dore
Expression of Cyclo-oxygenase-2 in Naturally Occurring Squamous Cell Carcinomas in Dogs
J. Histochem. Cytochem., July 1, 2001; 49(7): 867 - 876.
[Abstract] [Full Text] [PDF]

S. Kern, R. Hruban, M. A. Hollingsworth, R. Brand, T. E. Adrian, E. Jaffee, and M. A. Tempero
A White Paper: The Product of a Pancreas Cancer Think Tank
Cancer Res., June 1, 2001; 61(12): 4923 - 4932.
[Full Text] [PDF]

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]

K. Subbaramaiah, P. Bulic, Y. Lin, A. J. Dannenberg, and D. S. Pasco
Development and Use of a Gene Promoter-Based Screen to Identify Novel Inhibitors of Cyclooxygenase-2 Transcription
J Biomol Screen, April 1, 2001; 6(2): 101 - 110.
[Abstract] [PDF]

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]

T. Shirahama and C. Sakakura
Overexpression of Cyclooxygenase-2 in Squamous Cell Carcinoma of the Urinary Bladder
Clin. Cancer Res., March 1, 2001; 7(3): 558 - 561.
[Abstract] [Full Text]

H. Shiotani, A. Denda, K. Yamamoto, W. Kitayama, T. Endoh, Y. Sasaki, M. Tsutsumi, M. Sugimura, and Y. Konishi
Increased Expression of Cyclooxygenase-2 Protein in 4-Nitroquinoline-1-oxide-induced Rat Tongue Carcinomas and Chemopreventive Efficacy of a Specific Inhibitor, Nimesulide
Cancer Res., February 1, 2001; 61(4): 1451 - 1456.
[Abstract] [Full Text]

S. Kulkarni, J. S. Rader, F. Zhang, H. Liapis, A. T. Koki, J. L. Masferrer, K. Subbaramaiah, and A. J. Dannenberg
Cyclooxygenase-2 Is Overexpressed in Human Cervical Cancer
Clin. Cancer Res., February 1, 2001; 7(2): 429 - 434.
[Abstract] [Full Text]

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]

C. Denkert, M. Köbel, S. Berger, A. Siegert, A. Leclere, U. Trefzer, and S. Hauptmann
Expression of Cyclooxygenase 2 in Human Malignant Melanoma
Cancer Res., January 1, 2001; 61(1): 303 - 308.
[Abstract] [Full Text]

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]

S. H. HONG, F. G. ONDREY, I. M. AVIS, Z. CHEN, E. LOUKINOVA, P. F. CAVANAUGH JR, C. VAN WAES, and J. L. MULSHINE
Cyclooxygenase regulates human oropharyngeal carcinomas via the proinflammatory cytokine IL-6: a general role for inflammation?
FASEB J, August 1, 2000; 14(11): 1499 - 1507.
[Abstract] [Full Text]

R. H. Hruban, M. Goggins, J. Parsons, and S. E. Kern
Progression Model for Pancreatic Cancer
Clin. Cancer Res., August 1, 2000; 6(8): 2969 - 2972.
[Full Text]

M. Komhoff, Y. Guan, H. W. Shappell, L. Davis, G. Jack, Y. Shyr, M. O. Koch, S. B. Shappell, and M. D. Breyer
Enhanced Expression of Cyclooxygenase-2 in High Grade Human Transitional Cell Bladder Carcinomas
Am. J. Pathol., July 1, 2000; 157(1): 29 - 35.
[Abstract] [Full Text] [PDF]

T. Shirahama
Cyclooxygenase-2 Expression Is Up-Regulated in Transitional Cell Carcinoma and Its Preneoplastic Lesions in the Human Urinary Bladder
Clin. Cancer Res., June 1, 2000; 6(6): 2424 - 2430.
[Abstract] [Full Text]

C. Petersen, S. Petersen, L. Milas, F. F. Lang, and P. J. Tofilon
Enhancement of Intrinsic Tumor Cell Radiosensitivity Induced by a Selective Cyclooxygenase-2 Inhibitor
Clin. Cancer Res., June 1, 2000; 6(6): 2513 - 2520.
[Abstract] [Full Text]

R. H. Hruban, R. E. Wilentz, and S. E. Kern
Genetic Progression in the Pancreatic Ducts
Am. J. Pathol., June 1, 2000; 156(6): 1821 - 1825.
[Abstract] [Full Text] [PDF]

K. Subbaramaiah, P. Michaluart, M. B. Sporn, and A. J. Dannenberg
Ursolic Acid Inhibits Cyclooxygenase-2 Transcription in Human Mammary Epithelial Cells
Cancer Res., May 1, 2000; 60(9): 2399 - 2404.
[Abstract] [Full Text]

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]

M. B. Sporn and N. Suh
Chemoprevention of cancer
Carcinogenesis, March 1, 2000; 21(3): 525 - 530.
[Abstract] [Full Text] [PDF]

J. L. Masferrer, K. M. Leahy, A. T. Koki, B. S. Zweifel, S. L. Settle, B. M. Woerner, D. A. Edwards, A. G. Flickinger, R. J. Moore, and K. Seibert
Antiangiogenic and Antitumor Activities of Cyclooxygenase-2 Inhibitors
Cancer Res., March 1, 2000; 60(5): 1306 - 1311.
[Abstract] [Full Text]

, , , , , J. , P. , and
Preferential Enhancement of Tumor Radioresponse by a Cyclooxygenase-2
Cancer Res., March 1, 2000; 60(5): 1326 - 1331.
[Abstract] [Full Text] [PDF]

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]

M. Stolina, S. Sharma, Y. Lin, M. Dohadwala, B. Gardner, J. Luo, L. Zhu, M. Kronenberg, P. W. Miller, J. Portanova, et al.
Specific Inhibition of Cyclooxygenase 2 Restores Antitumor Reactivity by Altering the Balance of IL-10 and IL-12 Synthesis
J. Immunol., January 1, 2000; 164(1): 361 - 370.
[Abstract] [Full Text] [PDF]