This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sano, H. Articles by Hla, T. Search for Related Content PubMed PubMed Citation Articles by Sano, H. Articles by Hla, T.

Expression of Cyclooxygenase-1 and -2 in Human Colorectal Cancer¹

First Department of Internal Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602, Japan [H. S., Y. K., A. H., S. M., K. A., S. K., H. K., M. K.]; Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland 20892 [R. L. W.]; and Department of Molecular Biology, Holland Laboratory, American Red Cross, Rockville, Maryland 20855 [T. H.]

Several studies indicate that nonsteroidal anti-inflammatory drugs including indomethacin, aspirin, sulindac, and piroxicam reduce the risk of colon cancer. Furthermore, nonsteroidal anti-inflammatory drugs that inhibit the cyclooxygenase (COX) enzyme were shown to inhibit the development of colon cancer in animal models of carcinogenesis. Nonsteroidal anti-inflammatory drugs inhibit the enzymatic activity of both the constitutive (COX-1) and inducible (COX-2) isoforms of COX enzyme. We have investigated the expression of COX-1 and COX-2 polypeptides in human colon cancer tissues using immunohistochemistry. Enhanced COX-2 expression was observed in colon cancer tissues from 15 subjects with clinically diagnosed colorectal cancer. Marked COX-2 expression was observed in cancer cells, inflammatory cells, vascular endothelium, and fibroblasts of the lesional tissues compared with the nonlesional and normal colon tissues. The extent and intensity of the immunoreactive COX-2 in cancer cells was much greater than that of the other cell types. In contrast, the expression of COX-1 polypeptide was weak in both normal and cancerous specimens. These data suggest that the enhanced expression of the COX-2 gene in colon cancer tissues may contribute to the enhanced synthesis of prostaglandin E₂ by the colon cancer tissues. Enhanced expression of COX-2 may play a role in the pathogenesis of colon cancer. Furthermore, selective inhibition of COX-2 may prove to be more efficacious in the retardation of colon cancer development.

¹ This work was supported by a Grant-in-Aid for scientific research from the Ministry of Education, Science, and Culture of Japan, by the Inamori Foundation, and by the Japan Rheumatism Foundation (H. S.) and NIH Grants HL 49094 and DK 45659 (T. H.).

² To whom requests for reprints should be addressed.

Received 4/18/95. Accepted 7/ 5/95.

This article has been cited by other articles:

				R. Sirianni, A. Chimento, A. De Luca, F. Zolea, A. Carpino, V. Rago, M. Maggiolini, S. Ando, and V. Pezzi Inhibition of Cyclooxygenase-2 Down-regulates Aromatase Activity and Decreases Proliferation of Leydig Tumor Cells J. Biol. Chem., October 16, 2009; 284(42): 28905 - 28916. [Abstract] [Full Text] [PDF]

				E. L. Barry, L. B. Sansbury, M. V. Grau, I. U. Ali, S. Tsang, D. J. Munroe, D. J. Ahnen, R. S. Sandler, F. Saibil, J. Gui, et al. Cyclooxygenase-2 Polymorphisms, Aspirin Treatment, and Risk for Colorectal Adenoma Recurrence--Data from a Randomized Clinical Trial Cancer Epidemiol. Biomarkers Prev., October 1, 2009; 18(10): 2726 - 2733. [Abstract] [Full Text] [PDF]

				G. Heiduschka, B. M. Erovic, L. Vormittag, C. Skoda, H. Martinek, M. Brunner, K. Ehrenberger, and D. Thurnher 7{beta}-Hydroxycholesterol Induces Apoptosis and Regulates Cyclooxygenase 2 in Head and Neck Squamous Cell Carcinoma Arch Otolaryngol Head Neck Surg, March 1, 2009; 135(3): 261 - 267. [Abstract] [Full Text] [PDF]

				T. Nakagawa, H. Tanaka, T. Shirakawa, A. Gotoh, Y. Hayashi, K. Hamada, M. Tsukuda, and K.-i. Nibu Cyclooxygenase 2 Promoter-Based Replication-Selective Adenoviral Vector for Hypopharyngeal Cancer Arch Otolaryngol Head Neck Surg, March 1, 2009; 135(3): 282 - 286. [Abstract] [Full Text] [PDF]

				A. Greenhough, H. J.M. Smartt, A. E. Moore, H. R. Roberts, A. C. Williams, C. Paraskeva, and A. Kaidi The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment Carcinogenesis, March 1, 2009; 30(3): 377 - 386. [Abstract] [Full Text] [PDF]

				D G Binion, M F Otterson, and P Rafiee Curcumin inhibits VEGF-mediated angiogenesis in human intestinal microvascular endothelial cells through COX-2 and MAPK inhibition Gut, November 1, 2008; 57(11): 1509 - 1517. [Abstract] [Full Text] [PDF]

				L. Mastrangelo, A. Cassidy, F. Mulholland, W. Wang, and Y. Bao Serotonin Receptors, Novel Targets of Sulforaphane Identified by Proteomic Analysis in Caco-2 Cells Cancer Res., July 1, 2008; 68(13): 5487 - 5491. [Abstract] [Full Text] [PDF]

				I. M. Macias-Perez, R. Zent, M. Carmosino, M. D. Breyer, R. M. Breyer, and A. Pozzi Mouse EP3 {alpha}, {beta}, and {gamma} Receptor Variants Reduce Tumor Cell Proliferation and Tumorigenesis in Vivo J. Biol. Chem., May 2, 2008; 283(18): 12538 - 12545. [Abstract] [Full Text] [PDF]

				M. N. Hall, J. E. Chavarro, I-M. Lee, W. C. Willett, and J. Ma A 22-year Prospective Study of Fish, n-3 Fatty Acid Intake, and Colorectal Cancer Risk in Men Cancer Epidemiol. Biomarkers Prev., May 1, 2008; 17(5): 1136 - 1143. [Abstract] [Full Text] [PDF]

				M.-R. Pan, M.-F. Hou, H.-C. Chang, and W.-C. Hung Cyclooxygenase-2 Up-regulates CCR7 via EP2/EP4 Receptor Signaling Pathways to Enhance Lymphatic Invasion of Breast Cancer Cells J. Biol. Chem., April 25, 2008; 283(17): 11155 - 11163. [Abstract] [Full Text] [PDF]

				V. A. Papadimitrakopoulou, W. N. William Jr., A. J. Dannenberg, S. M. Lippman, J. J. Lee, F. G. Ondrey, D. E. Peterson, L. Feng, A. Atwell, A. K. El-Naggar, et al. Pilot Randomized Phase II Study of Celecoxib in Oral Premalignant Lesions Clin. Cancer Res., April 1, 2008; 14(7): 2095 - 2101. [Abstract] [Full Text] [PDF]

				A. B. Kunnumakkara, P. Diagaradjane, S. Guha, A. Deorukhkar, S. Shentu, B. B. Aggarwal, and S. Krishnan Curcumin Sensitizes Human Colorectal Cancer Xenografts in Nude Mice to {gamma}-Radiation by Targeting Nuclear Factor-{kappa}B-Regulated Gene Products Clin. Cancer Res., April 1, 2008; 14(7): 2128 - 2136. [Abstract] [Full Text] [PDF]

				M. T. Accioly, P. Pacheco, C. M. Maya-Monteiro, N. Carrossini, B. K. Robbs, S. S. Oliveira, C. Kaufmann, J. A. Morgado-Diaz, P. T. Bozza, and J. P.B. Viola Lipid Bodies Are Reservoirs of Cyclooxygenase-2 and Sites of Prostaglandin-E2 Synthesis in Colon Cancer Cells Cancer Res., March 15, 2008; 68(6): 1732 - 1740. [Abstract] [Full Text] [PDF]

				R. H. Nakamoto, H. Uetake, S. Iida, Y. V. Kolev, L. T. Soumaoro, Y. Takagi, M. Yasuno, and K. Sugihara Correlations between Cyclooxygenase-2 Expression and Angiogenic Factors in Primary Tumors and Liver Metastases in Colorectal Cancer Jpn. J. Clin. Oncol., September 10, 2007; (2007) hym080v1. [Abstract] [Full Text] [PDF]

				N. Iwase, T. Higuchi, T. Gonda, H. Kobayashi, H. Uetake, M. Enomoto, and K. Sugihara The Effect of Meloxicam, a Selective COX-2 Inhibitor, on the Microvasculature of Small Metastatic Liver Tumors in Rats Jpn. J. Clin. Oncol., September 1, 2007; 37(9): 673 - 678. [Abstract] [Full Text] [PDF]

				B. Samuelsson, R. Morgenstern, and P.-J. Jakobsson Membrane Prostaglandin E Synthase-1: A Novel Therapeutic Target Pharmacol. Rev., September 1, 2007; 59(3): 207 - 224. [Abstract] [Full Text] [PDF]

				T. Hall-Pogar, S. Liang, L. K. Hague, and C. S. Lutz Specific trans-acting proteins interact with auxiliary RNA polyadenylation elements in the COX-2 3'-UTR RNA, July 1, 2007; 13(7): 1103 - 1115. [Abstract] [Full Text] [PDF]

				K. Xu and H.-K. G. Shu EGFR Activation Results in Enhanced Cyclooxygenase-2 Expression through p38 Mitogen-Activated Protein Kinase-Dependent Activation of the Sp1/Sp3 Transcription Factors in Human Gliomas Cancer Res., July 1, 2007; 67(13): 6121 - 6129. [Abstract] [Full Text] [PDF]

				J.-Y. Liou, D. Ghelani, S. Yeh, and K. K. Wu Nonsteroidal Anti-inflammatory Drugs Induce Colorectal Cancer Cell Apoptosis by Suppressing 14-3-3{varepsilon} Cancer Res., April 1, 2007; 67(7): 3185 - 3191. [Abstract] [Full Text] [PDF]

				M. N. Hall, H. Campos, H. Li, H. D. Sesso, M. J. Stampfer, W. C. Willett, and J. Ma Blood Levels of Long-Chain Polyunsaturated Fatty Acids, Aspirin, and the Risk of Colorectal Cancer Cancer Epidemiol. Biomarkers Prev., February 1, 2007; 16(2): 314 - 321. [Abstract] [Full Text] [PDF]

				T Andre, C Tournigand, L Mineur, R Fellague-Chebra, M Flesch, M Mabro, M Hebbar, S Postel Vinay, F. Bidard, C Louvet, et al. Phase II study of an optimized 5-fluorouracil-oxaliplatin strategy (OPTIMOX2) with celecoxib in metastatic colorectal cancer: a GERCOR study Ann. Onc., January 1, 2007; 18(1): 77 - 81. [Abstract] [Full Text] [PDF]

				A. Mahipal, K. E. Anderson, P. J. Limburg, and A. R. Folsom Nonsteroidal Anti-inflammatory Drugs and Subsite-Specific Colorectal Cancer Incidence in the Iowa Women's Health Study. Cancer Epidemiol. Biomarkers Prev., October 1, 2006; 15(10): 1785 - 1790. [Abstract] [Full Text] [PDF]

				A. M. Monjazeb, K. P. High, A. Connoy, L. S. Hart, C. Koumenis, and F. H. Chilton Arachidonic acid-induced gene expression in colon cancer cells Carcinogenesis, October 1, 2006; 27(10): 1950 - 1960. [Abstract] [Full Text] [PDF]

				J. S. Munday, M. M. Brennan, and M. Kiupel Altered Expression of {beta}-catenin, E-cadherin, Cycloxygenase-2, and p53 Protein by Ovine Intestinal Adenocarcinoma Cells. Vet. Pathol., September 1, 2006; 43(5): 613 - 621. [Abstract] [Full Text] [PDF]

				O. K. Glebov, L. M. Rodriguez, P. Lynch, S. Patterson, H. Lynch, K. Nakahara, J. Jenkins, J. Cliatt, C.-J. Humbyrd, J. DeNobile, et al. Celecoxib treatment alters the gene expression profile of normal colonic mucosa. Cancer Epidemiol. Biomarkers Prev., July 1, 2006; 15(7): 1382 - 1391. [Abstract] [Full Text] [PDF]

				K J Schmitz, R Callies, J Wohlschlaeger, R Kimmig, F Otterbach, J Bohr, H-S Lee, A Takeda, K W Schmid, and H A Baba Overexpression of cyclo-oxygenase-2 is an independent predictor of unfavourable outcome in node-negative breast cancer, but is not associated with protein kinase B (Akt) and mitogen-activated protein kinase (ERK1/2, p38) activation or with Her-2/neu signalling pathways J. Clin. Pathol., July 1, 2006; 59(7): 685 - 691. [Abstract] [Full Text] [PDF]

				G. Cohen, R. Mustafi, A. Chumsangsri, N. Little, J. Nathanson, S. Cerda, S. Jagadeeswaran, U. Dougherty, L. Joseph, J. Hart, et al. Epidermal Growth Factor Receptor Signaling Is Up-regulated in Human Colonic Aberrant Crypt Foci Cancer Res., June 1, 2006; 66(11): 5656 - 5664. [Abstract] [Full Text] [PDF]

				H. Zhi, L. Wang, J. Zhang, C. Zhou, F. Ding, A. Luo, M. Wu, Q. Zhan, and Z. Liu Significance of COX-2 expression in human esophageal squamous cell carcinoma Carcinogenesis, June 1, 2006; 27(6): 1214 - 1221. [Abstract] [Full Text] [PDF]

				J. Vanamala, T. Leonardi, B. S. Patil, S. S. Taddeo, M. E. Murphy, L. M. Pike, R. S. Chapkin, J. R. Lupton, and N. D. Turner Suppression of colon carcinogenesis by bioactive compounds in grapefruit Carcinogenesis, June 1, 2006; 27(6): 1257 - 1265. [Abstract] [Full Text] [PDF]

				K. Nagata, K. Wada, A. Tatsuguchi, S. Futagami, K. Gudis, K. Miyake, T. Tsukui, and C. Sakamoto Heregulin-{alpha} and heregulin-beta expression is linked to a COX-2-PGE2 pathway in human gastric fibroblasts Am J Physiol Gastrointest Liver Physiol, June 1, 2006; 290(6): G1243 - G1251. [Abstract] [Full Text] [PDF]

				L. B. Sansbury, A. W. Bergen, K. L. Wanke, B. Yu, N. E. Caporaso, N. Chatterjee, L. Ratnasinghe, A. Schatzkin, T. A. Lehman, A. Kalidindi, et al. Inflammatory cytokine gene polymorphisms, nonsteroidal anti-inflammatory drug use, and risk of adenoma polyp recurrence in the polyp prevention trial. Cancer Epidemiol. Biomarkers Prev., March 1, 2006; 15(3): 494 - 501. [Abstract] [Full Text] [PDF]

				R. Kaul, S. C. Verma, M. Murakami, K. Lan, T. Choudhuri, and E. S. Robertson Epstein-Barr Virus Protein Can Upregulate Cyclo-Oxygenase-2 Expression through Association with the Suppressor of Metastasis Nm23-H1 J. Virol., February 1, 2006; 80(3): 1321 - 1331. [Abstract] [Full Text] [PDF]

				G. Waris and A. Siddiqui Hepatitis C Virus Stimulates the Expression of Cyclooxygenase-2 via Oxidative Stress: Role of Prostaglandin E2 in RNA Replication J. Virol., August 1, 2005; 79(15): 9725 - 9734. [Abstract] [Full Text] [PDF]

				R. Fux, M. Schwab, K.-P. Thon, C. H. Gleiter, and P. Fritz Cyclooxygenase-2 Expression in Human Colorectal Cancer Is Unrelated to Overall Patient Survival Clin. Cancer Res., July 1, 2005; 11(13): 4754 - 4760. [Abstract] [Full Text] [PDF]

				L. Maggio-Price, H. Bielefeldt-Ohmann, P. Treuting, B. M. Iritani, W. Zeng, A. Nicks, M. Tsang, D. Shows, P. Morrissey, and J. L. Viney Dual Infection with Helicobacter bilis and Helicobacter hepaticus in P-Glycoprotein-Deficient mdr1a-/- Mice Results in Colitis that Progresses to Dysplasia Am. J. Pathol., June 1, 2005; 166(6): 1793 - 1806. [Abstract] [Full Text] [PDF]

				L. A.A. Brosens, C. A. Iacobuzio-Donahue, J. J. Keller, S. R. Hustinx, R. Carvalho, F. H. Morsink, L. M. Hylind, G. J. Offerhaus, F. M. Giardiello, and M. Goggins Increased Cyclooxygenase-2 Expression in Duodenal Compared with Colonic Tissues in Familial Adenomatous Polyposis and Relationship to the -765G -> C COX-2 Polymorphism Clin. Cancer Res., June 1, 2005; 11(11): 4090 - 4096. [Abstract] [Full Text] [PDF]

				T. Hall-Pogar, H. Zhang, B. Tian, and C. S. Lutz Alternative polyadenylation of cyclooxygenase-2 Nucleic Acids Res., May 4, 2005; 33(8): 2565 - 2579. [Abstract] [Full Text] [PDF]

				J. N. Davis, M. T. McCabe, S. W. Hayward, J. M. Park, and M. L. Day Disruption of Rb/E2F Pathway Results in Increased Cyclooxygenase-2 Expression and Activity in Prostate Epithelial Cells Cancer Res., May 1, 2005; 65(9): 3633 - 3642. [Abstract] [Full Text] [PDF]

				J. R. Brown and R. N. DuBois COX-2: A Molecular Target for Colorectal Cancer Prevention J. Clin. Oncol., April 20, 2005; 23(12): 2840 - 2855. [Abstract] [Full Text] [PDF]

				K. Oh, W. C. Willett, C. S. Fuchs, and E. Giovannucci Dietary Marine n-3 Fatty Acids in Relation to Risk of Distal Colorectal Adenoma in Women Cancer Epidemiol. Biomarkers Prev., April 1, 2005; 14(4): 835 - 841. [Abstract] [Full Text] [PDF]

				K. Oyama, T. Fujimura, I. Ninomiya, T. Miyashita, S. Kinami, S. Fushida, T. Ohta, and M. Koichi A COX-2 inhibitor prevents the esophageal inflammation-metaplasia-adenocarcinoma sequence in rats Carcinogenesis, March 1, 2005; 26(3): 565 - 570. [Abstract] [Full Text] [PDF]

				R. A. Lubet, K. Huebner, L. Y.Y. Fong, D. C. Altieri, V. E. Steele, L. Kopelovich, C. Kavanaugh, M.M. Juliana, S.-j. Soong, and C. J. Grubbs 4-Hydroxybutyl(butyl)nitrosamine-induced urinary bladder cancers in mice: characterization of FHIT and survivin expression and chemopreventive effects of indomethacin Carcinogenesis, March 1, 2005; 26(3): 571 - 578. [Abstract] [Full Text] [PDF]

				N. Niho, M. Mutoh, M. Takahashi, K. Tsutsumi, T. Sugimura, and K. Wakabayashi Concurrent suppression of hyperlipidemia and intestinal polyp formation by NO-1886, increasing lipoprotein lipase activity in Min mice PNAS, February 22, 2005; 102(8): 2970 - 2974. [Abstract] [Full Text] [PDF]

				T. Kawamori, T. Kitamura, K. Watanabe, N. Uchiya, T. Maruyama, S. Narumiya, T. Sugimura, and K. Wakabayashi Prostaglandin E receptor subtype EP1 deficiency inhibits colon cancer development Carcinogenesis, February 1, 2005; 26(2): 353 - 357. [Abstract] [Full Text] [PDF]

				P. Palozza, S. Serini, N. Maggiano, G. Tringali, P. Navarra, F. O. Ranelletti, and G. Calviello {beta}-Carotene Downregulates the Steady-State and Heregulin-{alpha}-Induced COX-2 Pathways in Colon Cancer Cells J. Nutr., January 1, 2005; 135(1): 129 - 136. [Abstract] [Full Text] [PDF]

				L. T. Soumaoro, H. Uetake, T. Higuchi, Y. Takagi, M. Enomoto, and K. Sugihara Cyclooxygenase-2 Expression: A Significant Prognostic Indicator for Patients With Colorectal Cancer Clin. Cancer Res., December 15, 2004; 10(24): 8465 - 8471. [Abstract] [Full Text] [PDF]

				H.-P. Lin, S. K. Kulp, P.-H. Tseng, Y.-T. Yang, C.-C. Yang, C.-S. Chen, and C.-S. Chen Growth inhibitory effects of celecoxib in human umbilical vein endothelial cells are mediated through G1 arrest via multiple signaling mechanisms Mol. Cancer Ther., December 1, 2004; 3(12): 1671 - 1680. [Abstract] [Full Text] [PDF]

				K. T. Nam, K.-B. Hahm, S.-Y. Oh, M. Yeo, S.-U. Han, B. Ahn, Y.-B. Kim, J. S. Kang, D. D. Jang, K.-H. Yang, et al. The Selective Cyclooxygenase-2 Inhibitor Nimesulide Prevents Helicobacter pylori-Associated Gastric Cancer Development in a Mouse Model Clin. Cancer Res., December 1, 2004; 10(23): 8105 - 8113. [Abstract] [Full Text] [PDF]

				A. E. Moran, D. H. Hunt, S. H. Javid, M. Redston, A. M. Carothers, and M. M. Bertagnolli Apc Deficiency Is Associated with Increased Egfr Activity in the Intestinal Enterocytes and Adenomas of C57BL/6J-Min/+ Mice J. Biol. Chem., October 8, 2004; 279(41): 43261 - 43272. [Abstract] [Full Text] [PDF]

				W.-C. Huang, S.-T. Chan, T.-L. Yang, C.-C. Tzeng, and C.-C. Chen Inhibition of ICAM-1 gene expression, monocyte adhesion and cancer cell invasion by targeting IKK complex: molecular and functional study of novel {alpha}-methylene-{gamma}-butyrolactone derivatives Carcinogenesis, October 1, 2004; 25(10): 1925 - 1934. [Abstract] [Full Text] [PDF]

				D. L. Simmons, R. M. Botting, and T. Hla Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition Pharmacol. Rev., September 1, 2004; 56(3): 387 - 437. [Abstract] [Full Text] [PDF]

				P. A. Adegboyega, O. Ololade, J. Saada, R. Mifflin, J. F. Di Mari, and D. W. Powell Subepithelial Myofibroblasts Express Cyclooxygenase-2 in Colorectal Tubular Adenomas Clin. Cancer Res., September 1, 2004; 10(17): 5870 - 5879. [Abstract] [Full Text] [PDF]

				C. M. Holland, S. A. Saidi, A. L. Evans, A. M. Sharkey, J. A. Latimer, R. A.F. Crawford, D. S. Charnock-Jones, C. G. Print, and S. K. Smith Transcriptome analysis of endometrial cancer identifies peroxisome proliferator-activated receptors as potential therapeutic targets Mol. Cancer Ther., August 1, 2004; 3(8): 993 - 1001. [Abstract] [Full Text] [PDF]

				T. Shirakawa, K. Hamada, Z. Zhang, H. Okada, M. Tagawa, S. Kamidono, M. Kawabata, and A. Gotoh A Cox-2 Promoter-Based Replication-Selective Adenoviral Vector to Target the Cox-2-Expressing Human Bladder Cancer Cells Clin. Cancer Res., July 1, 2004; 10(13): 4342 - 4348. [Abstract] [Full Text] [PDF]

				F. A. Sinicrope, E. Half, J. S. Morris, P. M. Lynch, J. D. Morrow, B. Levin, E. T. Hawk, D. S. Cohen, G. D. Ayers, and L. C. Stephens Cell Proliferation and Apoptotic Indices Predict Adenoma Regression in a Placebo-Controlled Trial of Celecoxib in Familial Adenomatous Polyposis Patients Cancer Epidemiol. Biomarkers Prev., June 1, 2004; 13(6): 920 - 927. [Abstract] [Full Text] [PDF]

				T. KUWANO, S. NAKAO, H. YAMAMOTO, M. TSUNEYOSHI, T. YAMAMOTO, M. KUWANO, and M. ONO Cyclooxygenase 2 is a key enzyme for inflammatory cytokine-induced angiogenesis FASEB J, February 1, 2004; 18(2): 300 - 310. [Abstract] [Full Text] [PDF]

				J.-L. Su, J.-Y. Shih, M.-L. Yen, Y.-M. Jeng, C.-C. Chang, C.-Y. Hsieh, L.-H. Wei, P.-C. Yang, and M.-L. Kuo Cyclooxygenase-2 Induces EP1- and HER-2/Neu-Dependent Vascular Endothelial Growth Factor-C Up-Regulation: A Novel Mechanism of Lymphangiogenesis in Lung Adenocarcinoma Cancer Res., January 15, 2004; 64(2): 554 - 564. [Abstract] [Full Text] [PDF]

				T. Sato, K. Yoshinaga, S. Okabe, T. Okawa, T. Higuchi, M. Enomoto, T. Takizawa, and K. Sugihara Cyclooxygenase-2 Expression and its Relationship with Proliferation of Colorectal Adenomas Jpn. J. Clin. Oncol., December 1, 2003; 33(12): 631 - 635. [Abstract] [Full Text] [PDF]

				B. V.V. Pardhasaradhi, A. M. Ali, A. L. Kumari, P. Reddanna, and A. Khar Phycocyanin-mediated apoptosis in AK-5 tumor cells involves down-regulation of Bcl-2 and generation of ROS Mol. Cancer Ther., November 1, 2003; 2(11): 1165 - 1170. [Abstract] [Full Text] [PDF]

				J. M Herendeen and C. Lindley Use of NSAIDs for the Chemoprevention of Colorectal Cancer Ann. Pharmacother., November 1, 2003; 37(11): 1664 - 1674. [Abstract] [Full Text] [PDF]

				S.-J. Yeo, J.-G. Yoon, and A.-K. Yi Myeloid Differentiation Factor 88-dependent Post-transcriptional Regulation of Cyclooxygenase-2 Expression by CpG DNA: TUMOR NECROSIS FACTOR-{alpha} RECEPTOR-ASSOCIATED FACTOR 6, A DIVERGING POINT IN THE Toll-LIKE RECEPTOR 9-SIGNALING J. Biol. Chem., October 17, 2003; 278(42): 40590 - 40600. [Abstract] [Full Text] [PDF]

				J. Y. Lee, J. Ye, Z. Gao, H. S. Youn, W. H. Lee, L. Zhao, N. Sizemore, and D. H. Hwang Reciprocal Modulation of Toll-like Receptor-4 Signaling Pathways Involving MyD88 and Phosphatidylinositol 3-Kinase/AKT by Saturated and Polyunsaturated Fatty Acids J. Biol. Chem., September 26, 2003; 278(39): 37041 - 37051. [Abstract] [Full Text] [PDF]

				K.-S. Chun, Y.-S. Keum, S. S. Han, Y.-S. Song, S.-H. Kim, and Y.-J. Surh Curcumin inhibits phorbol ester-induced expression of cyclooxygenase-2 in mouse skin through suppression of extracellular signal-regulated kinase activity and NF-{kappa}B activation Carcinogenesis, September 1, 2003; 24(9): 1515 - 1524. [Abstract] [Full Text] [PDF]

				H. Nishihara, S. Kizaka-Kondoh, P. A. Insel, and L. Eckmann Inhibition of apoptosis in normal and transformed intestinal epithelial cells by cAMP through induction of inhibitor of apoptosis protein (IAP)-2 PNAS, July 22, 2003; 100(15): 8921 - 8926. [Abstract] [Full Text] [PDF]

				W. Liu, N. Reinmuth, O. Stoeltzing, A. A. Parikh, C. Tellez, S. Williams, Y. D. Jung, F. Fan, A. Takeda, M. Akagi, et al. Cyclooxygenase-2 Is Up-Regulated by Interleukin-1{beta} in Human Colorectal Cancer Cells via Multiple Signaling Pathways Cancer Res., July 1, 2003; 63(13): 3632 - 3636. [Abstract] [Full Text] [PDF]

				R. N. DuBois Evaluation of the Whole Prostaglandin Biosynthetic Pathway in Lung Cancer Clin. Cancer Res., May 1, 2003; 9(5): 1577 - 1578. [Full Text] [PDF]

				T. Inaba, H. Sano, Y. Kawahito, T. Hla, K. Akita, M. Toda, I. Yamashina, M. Inoue, and H. Nakada Induction of cyclooxygenase-2 in monocyte/macrophage by mucins secreted from colon cancer cells PNAS, March 4, 2003; 100(5): 2736 - 2741. [Abstract] [Full Text] [PDF]

				J. Y. Lee, A. Plakidas, W. H. Lee, A. Heikkinen, P. Chanmugam, G. Bray, and D. H. Hwang Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids J. Lipid Res., March 1, 2003; 44(3): 479 - 486. [Abstract] [Full Text] [PDF]

				R. K. Wali, S. Khare, M. Tretiakova, G. Cohen, L. Nguyen, J. Hart, J. Wang, M. Wen, A. Ramaswamy, L. Joseph, et al. Ursodeoxycholic Acid and F6-D3 Inhibit Aberrant Crypt Proliferation in the Rat Azoxymethane Model of Colon Cancer: Roles of Cyclin D1 and E-Cadherin Cancer Epidemiol. Biomarkers Prev., December 1, 2002; 11(12): 1653 - 1662. [Abstract] [Full Text] [PDF]

				H. J. Lin, K. M. Lakkides, T. O. Keku, S. T. Reddy, A. D. Louie, I. H. Kau, H. Zhou, J. S. Y. Gim, H. L. Ma, C. F. Matthies, et al. Prostaglandin H Synthase 2 Variant (Val511Ala) in African Americans May Reduce the Risk for Colorectal Neoplasia Cancer Epidemiol. Biomarkers Prev., November 1, 2002; 11(11): 1305 - 1315. [Abstract] [Full Text] [PDF]

				K.-i. Sunayama, H. Konno, T. Nakamura, H. Kashiwabara, T. Shoji, T. Tsuneyoshi, and S. Nakamura The role of cyclooxygenase-2 (COX-2) in two different morphological stages of intestinal polyps in APC{Delta}474 knockout mice Carcinogenesis, August 1, 2002; 23(8): 1351 - 1359. [Abstract] [Full Text] [PDF]

				P. S. Carlton, R. Gopalakrishnan, A. Gupta, B. W. Liston, S. Habib, M. A. Morse, and G. D. Stoner Piroxicam Is an Ineffective Inhibitor of N-Nitrosomethylbenzylamine-induced Tumorigenesis in the Rat Esophagus Cancer Res., August 1, 2002; 62(15): 4376 - 4382. [Abstract] [Full Text] [PDF]

				M. Tamura, S. Sebastian, S. Yang, B. Gurates, K. Ferrer, H. Sasano, K. Okamura, and S. E. Bulun Up-regulation of Cyclooxygenase-2 Expression and Prostaglandin Synthesis in Endometrial Stromal Cells by Malignant Endometrial Epithelial Cells. A PARACRINE EFFECT MEDIATED BY PROSTAGLANDIN E2 AND NUCLEAR FACTOR-kappa B J. Biol. Chem., July 12, 2002; 277(29): 26208 - 26216. [Abstract] [Full Text] [PDF]

				M. F. McEntee, J. M. Cates, and N. Neilsen Cyclooxygenase-2 Expression in Spontaneous Intestinal Neoplasia of Domestic Dogs Vet. Pathol., July 1, 2002; 39(4): 428 - 436. [Abstract] [Full Text] [PDF]

				H. Tsunozaki, K. Yoshinaga, J. Kumagai, and K. Sugihara Cyclooxygenase-2 Overexpression in Colorectal Cancer is Associated with Non-polypoid Growth Jpn. J. Clin. Oncol., May 1, 2002; 32(5): 167 - 171. [Abstract] [Full Text] [PDF]

				A. R. Munkarah, R. Morris, P. Baumann, G. Deppe, J. Malone, M. P. Diamond, and G. M. Saed Effects of Prostaglandin E2 on Proliferation and Apoptosis of Epithelial Ovarian Cancer Cells Reproductive Sciences, May 1, 2002; 9(3): 168 - 173. [Abstract] [PDF]

				S. Chu, S. Rushdi, E.T. Zumpe, P. Mamers, D.L. Healy, T. Jobling, H.G. Burger, and P.J. Fuller FSH-regulated gene expression profiles in ovarian tumours and normal ovaries Mol. Hum. Reprod., May 1, 2002; 8(5): 426 - 433. [Abstract] [Full Text] [PDF]

				G. Davies, L.-A. Martin, N. Sacks, and M. Dowsett Cyclooxygenase-2 (COX-2), aromatase and breast cancer: a possible role for COX-2 inhibitors in breast cancer chemoprevention Ann. Onc., May 1, 2002; 13(5): 669 - 678. [Abstract] [Full Text] [PDF]

				D. K. Bol, R. B. Rowley, C.-P. Ho, B. Pilz, J. Dell, M. Swerdel, K. Kiguchi, S. Muga, R. Klein, and S. M. Fischer Cyclooxygenase-2 Overexpression in the Skin of Transgenic Mice Results in Suppression of Tumor Development Cancer Res., May 1, 2002; 62(9): 2516 - 2521. [Abstract] [Full Text] [PDF]

				C. Waskewich, R. D. Blumenthal, H. Li, R. Stein, D. M. Goldenberg, and J. Burton Celecoxib Exhibits the Greatest Potency amongst Cyclooxygenase (COX) Inhibitors for Growth Inhibition of COX-2-negative Hematopoietic and Epithelial Cell Lines Cancer Res., April 1, 2002; 62(7): 2029 - 2033. [Abstract] [Full Text] [PDF]

				T. Asano, J. Shoda, T. Ueda, T. Kawamoto, T. Todoroki, M. Shimonishi, T. Tanabe, Y. Sugimoto, A. Ichikawa, M. Mutoh, et al. Expressions of Cyclooxygenase-2 and Prostaglandin E-Receptors in Carcinoma of the Gallbladder: Crucial Role of Arachidonate Metabolism in Tumor Growth and Progression Clin. Cancer Res., April 1, 2002; 8(4): 1157 - 1167. [Abstract] [Full Text] [PDF]

				D. Sample, M. Wargovich, S. M. Fischer, N. Inamdar, P. Schwartz, X. Wang, K.-A. Do, F. A. Sinicrope, N. E. Day, D. E. G. Shuker, et al. A Dose-finding Study of Aspirin for Chemoprevention Utilizing Rectal Mucosal Prostaglandin E2 Levels as a Biomarker Cancer Epidemiol. Biomarkers Prev., March 1, 2002; 11(3): 275 - 279. [Abstract] [Full Text] [PDF]

				Y. Kakiuchi, S. Tsuji, M. Tsujii, H. Murata, N. Kawai, M. Yasumaru, A. Kimura, M. Komori, T. Irie, E. Miyoshi, et al. Cyclooxygenase-2 Activity Altered the Cell-Surface Carbohydrate Antigens on Colon Cancer Cells and Enhanced Liver Metastasis Cancer Res., March 1, 2002; 62(5): 1567 - 1572. [Abstract] [Full Text] [PDF]

				T. Niki, T. Kohno, S. Iba, Y. Moriya, Y. Takahashi, M. Saito, A. Maeshima, T. Yamada, Y. Matsuno, M. Fukayama, et al. Frequent Co-Localization of Cox-2 and Laminin-5 {gamma}2 Chain at the Invasive Front of Early-Stage Lung Adenocarcinomas Am. J. Pathol., March 1, 2002; 160(3): 1129 - 1141. [Abstract] [Full Text] [PDF]

				J. D. Wayne, E. K. Abdalla, R. A. Wolff, C. H. Crane, P. W.T. Pisters, and D. B. Evans Localized Adenocarcinoma of the Pancreas: The Rationale for Preoperative Chemoradiation Oncologist, February 1, 2002; 7(1): 34 - 45. [Abstract] [Full Text] [PDF]

				J. Portnow, S. Suleman, S. A. Grossman, S. Eller, and K. Carson A cyclooxygenase-2 (COX-2) inhibitor compared with dexamethasone in a survival study of rats with intracerebral 9L gliosarcomas Neuro-oncol, January 1, 2002; 4(1): 22 - 25. [Abstract] [PDF]

				C. V. Rao, C. Indranie, B. Simi, P. T. Manning, J. R. Connor, and B. S. Reddy Chemopreventive Properties of a Selective Inducible Nitric Oxide Synthase Inhibitor in Colon Carcinogenesis, Administered Alone or in Combination with Celecoxib, a Selective Cyclooxygenase-2 Inhibitor Cancer Res., January 1, 2002; 62(1): 165 - 170. [Abstract] [Full Text] [PDF]

				D. HWANG Modulation of the expression of cyclooxygenase-2 by fatty acids mediated through Toll-like receptor 4-derived signaling pathways FASEB J, December 1, 2001; 15(14): 2556 - 2564. [Abstract] [Full Text] [PDF]

				W. Thomas, Z. K. Ascott, D. Harmey, L. W. Slice, E. Rozengurt, and A. J. Lax Cytotoxic Necrotizing Factor from Escherichia coli Induces RhoA-Dependent Expression of the Cyclooxygenase-2 Gene Infect. Immun., November 1, 2001; 69(11): 6839 - 6845. [Abstract] [Full Text] [PDF]

				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]

				K. Salmenkivi, C. Haglund, A. Ristimaki, J. Arola, and P. Heikkila Increased Expression of Cyclooxygenase-2 in Malignant Pheochromocytomas J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5615 - 5619. [Abstract] [Full Text] [PDF]

				J. Fujita, J. R. Mestre, J. B. Zeldis, K. Subbaramaiah, and A. J. Dannenberg Thalidomide and Its Analogues Inhibit Lipopolysaccharide-mediated Induction of Cyclooxygenase-2 Clin. Cancer Res., November 1, 2001; 7(11): 3349 - 3355. [Abstract] [Full Text] [PDF]

				R. J. Bing, M. Miyataka, K. A. Rich, N. Hanson, X. Wang, H. D. Slosser, and S.-R. Shi Nitric Oxide, Prostanoids, Cyclooxygenase, and Angiogenesis in Colon and Breast Cancer Clin. Cancer Res., November 1, 2001; 7(11): 3385 - 3392. [Abstract] [Full Text] [PDF]

				Z. Han, P. Pantazis, J. H. Wyche, N. Kouttab, V. J. Kidd, and E. A. Hendrickson A Fas-associated Death Domain Protein-dependent Mechanism Mediates the Apoptotic Action of Non-steroidal Anti-inflammatory Drugs in the Human Leukemic Jurkat Cell Line J. Biol. Chem., October 12, 2001; 276(42): 38748 - 38754. [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]

				W.-L. Yang and H. Frucht Activation of the PPAR pathway induces apoptosis and COX-2 inhibition in HT-29 human colon cancer cells Carcinogenesis, September 1, 2001; 22(9): 1379 - 1383. [Abstract] [Full Text] [PDF]

				G. Lal, C. Ash, K. Hay, M. Redston, E. Kwong, B. Hancock, T. Mak, S. Kargman, J. F. Evans, and S. Gallinger Suppression of Intestinal Polyps in Msh2-deficient and Non-Msh2-deficient Multiple Intestinal Neoplasia Mice by a Specific Cyclooxygenase-2 Inhibitor and by a Dual Cyclooxygenase-1/2 Inhibitor Cancer Res., August 1, 2001; 61(16): 6131 - 6136. [Abstract] [Full Text] [PDF]

				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]