This Article Abstract 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 Chan, G. Articles by Dannenberg, A. J. Search for Related Content PubMed PubMed Citation Articles by Chan, G. Articles by Dannenberg, A. J.

Cyclooxygenase-2 Expression Is Up-Regulated in Squamous Cell Carcinoma of the Head and Neck¹

Departments of Medicine [G. C., E. K. Y., A. J. D.], Thoracic Surgery [F. Z.], and Pathology [R. A. S.], New York Presbyterian Hospital and Weill Medical College of Cornell University, Strang Cancer Prevention Center [F. Z., A. J. D.], Head and Neck Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center [J. O. B., P. G. S., J. P. S.], and Manhattan Eye, Ear, and Throat Hospital [D. E.], New York, NY 10021, and Searle Discovery Research, Monsanto Company, St. Louis, Missouri 63017 [A. T. K., B. M. W., J. L. M.]

	ABSTRACT

Top ABSTRACT Introduction Materials and Methods Results Discussion REFERENCES

 
The purpose of this study was to determine whether cyclooxygenase-2 (COX-2) was overexpressed in squamous cell carcinoma of the head and neck (HNSCC). Quantitative reverse transcription-PCR, immunoblotting, and immunohistochemistry were used to assess the expression of COX-2 in head and neck tissue. Mean levels of COX-2 mRNA were increased by nearly 150-fold in HNSCC (n = 24) compared with normal oral mucosa from healthy volunteers (n = 17). Additionally, there was about a 50-fold increase in amounts of COX-2 mRNA in normal-appearing epithelium adjacent to HNSCC (n = 10) compared with normal oral mucosa from healthy volunteers. Immunoblotting demonstrated that COX-2 protein was present in six of six cases of HNSCC but was undetectable in normal oral mucosa from healthy subjects. Immunohistochemical analysis showed that COX-2 was expressed in both HNSCC and adjacent normal-appearing epithelium. Taken together, these results suggest that COX-2 may be a target for the prevention or treatment of HNSCC.

	Introduction

Top ABSTRACT Introduction Materials and Methods Results Discussion REFERENCES

 
Head and neck cancer is a major, worldwide cause of morbidity and mortality. Over 40,000 cases of HNSCC³ occur per year in the United States alone (1) . Despite recent advances in radiotherapy and chemotherapy, the survival of patients with HNSCC has not improved significantly. Moreover, patients who have been cured of one cancer of the head and neck develop second primary carcinomas of the head and neck, lung, or esophagus at a rate approaching 4% per year (2) . Hence, new molecular targets are needed for the prevention and treatment of HNSCC and related cancers.

COXs catalyze the synthesis of PGs from arachidonic acid. There are two isoforms of COX. One is constitutively expressed (COX-1), and the other is inducible (COX-2; Ref. 3 ). The COX-2 gene is an immediate, early-response gene that is induced by growth factors, oncogenes, carcinogens, and tumor-promoting phorbol esters (3, 4, 5) . The constitutive isoform, COX-1, is essentially unaffected by these factors.

A large body of evidence from a variety of experimental systems suggests that COX-2 is important in carcinogenesis. COX-2 is up-regulated in transformed cells (3 , 6) and in malignant tissue (7, 8, 9, 10) . Oshima et al. (11) showed that knocking out the COX-2 gene caused a marked reduction in the number and size of intestinal polyps in a murine model of familial adenomatous polyposis, i.e., APC⁷¹⁶ knockout mice. COX-2 knockout mice also develop about 75% fewer chemically induced skin papillomas than control mice (12) . In addition to the genetic evidence implicating COX-2 in tumorigenesis, recently developed selective inhibitors of COX-2 inhibit intestinal tumor formation in experimental animals (11 , 13) . In this study, we investigated whether COX-2 was overexpressed in HNSCC compared with normal mucosa from healthy volunteers. Our data show that levels of COX-2 are increased in HNSCC and raise the possibility that selective inhibitors of COX-2 may be useful in the chemoprevention and/or treatment of this disease.

	Materials and Methods

Top ABSTRACT Introduction Materials and Methods Results Discussion REFERENCES

 
Materials.
COX-2 primers were from Life Technologies, Inc. (Grand Island, NY). RNeasy Mini kits were from Qiagen, Inc. (Santa Clarita, CA). GeneAmp RNA PCR kits were from Perkin-Elmer (Norwalk, CT). GenElute Agarose Spin Columns were from Supelco (Bellefonte, PA). Lowry protein assay kits and secondary antibody to IgG conjugated to horseradish peroxidase were from Sigma Chemical Co. (St. Louis, MO). The COX-2 standard for immunoblotting was from Cayman Chemical Co. (Ann Arbor, MI). The COX-2 polyclonal antibody, PG-27, was from Oxford Biomedical Research, Inc. (Oxford, MI). Western blotting detection reagents (ECL) were from Amersham Pharmacia Biotech. Streck tissue fixative was from Streck Laboratories, Inc. (Omaha, NE). The tyramide signal and amplification kit was from NEN Life Science. The Vector Blocking kit was from Vector Laboratory, Inc. (Burlingame, CA).

Patient Samples.
HNSCC was obtained from 24 patients who underwent resection of their tumors at Memorial Sloan-Kettering Cancer Center. Pieces (2 x 2-mm) of HNSCC were sharply excised, placed in sterile tubes, and frozen immediately in liquid nitrogen. In some cases, clinically normal contralateral or adjacent mucosa was also collected. These latter samples, which were histologically normal, are referred to as normal-appearing epithelium. Some samples were bisected before freezing; one-half of this tissue was used for immunohistochemistry, and the other half was used for quantitative RT-PCR and/or immunoblotting. Normal oral mucosa was obtained from 17 subjects; these individuals were nonsmoking, nondrinking healthy volunteers and patients undergoing ear, nose, and throat procedures for benign disease. All tissue samples for RT-PCR and Western blotting were stored at -80°C until analysis. Tissue for immunohistochemistry was placed in 5 ml of Streck tissue fixative for 12–24 h before processing. Informed consent was obtained from each patient. The study was approved by the Committees on Human Rights in Research at the participating institutions.

Western Blotting.
Frozen tissue was thawed in ice-cold lysis buffer containing 150 mM NaCl, 100 mM Tris-buffered saline (pH 8), 1% Tween 20, 50 mM diethyldithiocarbamate, 1 mM EDTA, and 1 mM phenylmethylsulfonyl fluoride. Tissues were sonicated for 20 s on ice and centrifuged at 10,000 x g for 10 min at 4°C to remove the particulate material. The protein concentration of the supernatant was measured using the Lowry protein assay kit. Immunoblot analysis for COX-2 was performed as in previous studies (4 , 5) .

Construction of a COX-2 Competitor Template Containing a Nucleotide Deletion.
A competitive RT-PCR deletion construct (mimic) for COX-2 was synthesized using a mutant sense primer (nucleotides 932–955 attached to nucleotides 1111–1130; 5'-GGTCTGGTGCCTGGTCTGATGATGGAGTGGCTATCACT TCAAAC-3') and an antisense primer (nucleotides 1634–1655; 5'-GTCCTTTCAAGGAGAA TGGTGC-3'), producing a 569-bp PCR product. The mutant sense primer contains the primer-binding sequence of endogenous target (from nucleotide 932 to 955) attached to the end of an intervening DNA sequence (a 156-bp deletion from nucleotides 956 to 1110). Thus, the mimic DNA has primer binding sequences identical to the target cDNA. The 569-bp mimic was further amplified using the sense primer (5'-GGTCTGGTGCCTGGTCTGATGATG-3') and the antisense primer (5'-GTCCTTTCAAGGAGAATGGTGC-3') in a reaction mixture containing 10 mM Tris-HCl (pH 8.3), 50 mM KCl, 2 mM MgCl₂, 0.2 mM deoxynucleotide triphosphate, 2.5 units AmpliTaq DNA polymerase, and 400 nM primers for 35 cycles consisting of denaturation at 94°C for 20 s, annealing at 60°C for 20 s, and extension at 72°C for 30 s in a Perkin-Elmer 2400 thermal cycler. The PCR products were electrophoresed on 1% agarose gels and gel-purified using GenElute Agarose Spin Columns according to the manufacturer’s protocol.

RNA Isolation and Reverse Transcription.
Total RNA was isolated from head and neck tissue (50 mg) using RNeasy Mini kits from Qiagen. Total RNA (0.6 µg) was reverse transcribed using the GeneAmp RNA PCR kit according to the manufacturer’s protocol.

Quantitative PCR for COX-2 in Human Head and Neck Tissue.
Each PCR was carried out in 25 µl of a reaction mix, containing 10 mM Tris-HCl (pH 8.3), 50 mM KCl, 2 mM MgCl₂, 0.2 mM deoxynucleotide triphosphate, 2.5 units AmpliTaq DNA polymerase, and 400 nM primers (sense primer, 5'-GGTCTGGTGCCTGGTCTGATGATG-3'; antisense primer, 5'-GTCCTTTCAAGGAGAATGGTGC-3'). Five-µl aliquots of the reverse-transcribed cDNA samples and various known amounts of COX-2 mimic (between 0.001 and 0.05 pg), adjusted to the abundance of the target cDNA, were added to the reaction mix and coamplified for 35 cycles: denaturation at 94°C for 20 s, annealing at 65°C for 20 s, extension at 72°C for 90 s, and final extension at 72°C for 10 min. Ten µl of PCR products, 724-bp fragments from endogenous target cDNA, and 569-bp fragments from mimic COX-2 were then separated by electrophoresis on 1% agarose gels and visualized by ethidium bromide staining. A computer densitometer (Eagle Eye II; Stratagene, La Jolla, CA) was used to determine the density of the bands. A comparison of the band densities yielded the quantity of COX-2 mRNA in the reaction.

Immunohistochemistry.
Tissues from 10 patients with HNSCC were fixed in Streck’s solution, embedded in paraffin, cut into 4-µm sections, and mounted onto polylysine-coated slides. Sections were dewaxed in xylene, rehydrated in descending alcohols, and blocked for endogenous peroxidase (3% H₂O₂ in methanol) and avidin/biotin (Vector Blocking kit). The sections were permeabilized in TNB-BB [0.1 M Tris (pH 7.5), 0.15 M NaCl, 0.5% blocking agent, 0.3% Triton-X, and 0.2% saponin] and incubated in primary antibody overnight at 4°C. The polyclonal antiserum to COX-2 (PG-27; Oxford Biomedical Research, Inc.) was used at a 1:500 dilution in TNB-BB. Control sections were incubated with antisera in the presence of a 100-fold excess of human recombinant COX-2 protein or with isotype-matched IgG normal rabbit serum. Immunoreactive complexes were detected using tyramide signal amplification (TSA-indirect) and visualized with the peroxidase substrate, AEC. Slides were then counterstained in aqueous hematoxylin, mounted in crystal mount, and coverslipped in 50:50 xylene/Permount.

Statistics.
Comparisons between groups were made by the Student’s t test. A difference between groups of P < 0.05 was considered significant.

	Results

Top ABSTRACT Introduction Materials and Methods Results Discussion REFERENCES

 
To analyze the expression of COX-2, we developed a sensitive competitive RT-PCR assay in which the amount of COX-2 mRNA could be measured from small quantities of RNA. This method relies on the coamplification in the same tube of known amounts of competitor DNA with COX-2 cDNA obtained after reverse transcription from total tissue RNA. The competitor and target use the same PCR primers but yield amplicons with a different size (Fig. 1A) , allowing their separation on a gel at the end of the reaction. There was nearly a 150-fold increase in amounts of COX-2 mRNA in HNSCC (mean, 350 fg/µg total RNA) versus normal mucosa (mean, 2.4 fg/µg total RNA; Fig. 1B ). Interestingly, levels of COX-2 mRNA were also increased, although to a lesser degree, in normal-appearing epithelium adjacent to HNSCC (mean, 106 fg/µg total RNA) compared with normal mucosa. We also compared levels of COX-2 mRNA in paired samples of HNSCC and the adjacent normal-appearing epithelium. As shown in Fig. 1C , levels of COX-2 mRNA were consistently higher in HNSCC. Increased expression of COX-2 was detected in HNSCC from all sites in the head and neck (Table 1) .

View larger version (22K): [in this window] [in a new window] [Download PPT slide]   Fig. 1. Increased levels of COX-2 mRNA in HNSCC. A, representative quantitative RT-PCR in a case of HNSCC. Ten µl of endogenous cDNA and known concentrations (0.001–0.05 pg) of hCOX-2 mimic are competing for a fixed amount of hCOX-2 primer in each reaction lane, giving rise to relative proportions of 569-bp mimic product and 724-bp target cDNA product. In this case, there are equal amounts of both products formed at the mimic concentration of 0.01 pg, indicating that 10 µl of target cDNA are equivalent to 0.01 pg of COX-2 mimic. This is calculated to be 340 fg of COX-2 mRNA/µg of total RNA. B, quantitative RT-PCR was used to determine the amounts of COX-2 mRNA in 24 cases of HNSCC (mean, 350 fg/µg of total RNA; SD, 394 fg/µg of total RNA) and 17 cases of normal oral mucosa (mean, 2.4 fg/µg; SD, 4 fg/µg of total RNA). Nearly a 150-fold increase in amounts of COX-2 mRNA was detected in HNSCC versus normal oral mucosa (P < 0.001). C, quantitative RT-PCR was used to determine amounts of COX-2 mRNA in 10 pairs of HNSCC and in adjacent normal-appearing epithelium (Nontumor). Lines connect values for samples of HNSCC and adjacent normal-appearing epithelium from the same patients.

View larger version (18K): [in this window] [in a new window] [Download PPT slide]   Fig. 2. Levels of COX-2 protein are increased in HNSCC. Immunoblotting was performed on HNSCC from six patients (odd lanes) and normal oral mucosa from six healthy volunteers (even lanes). Equal amounts of protein (100 µg/lane) were loaded onto a 10% SDS-polyacrylamide gel, electrophoresed, and subsequently transferred onto nitrocellulose. The immunoblot was probed with antibody specific for COX-2. Purified ovine COX-2 was used as a standard.

View larger version (128K): [in this window] [in a new window] [Download PPT slide]   Fig. 3. COX-2 is expressed in malignant epithelial cells in HNSCC. A, this invasive, moderately differentiated squamous cell carcinoma shows diffuse and intense granular cytoplasmic immunoreactivity with anti-COX-2 antibody (x100). B, severe dysplasia shows moderately intense cytoplasmic COX-2 expression that is most apparent in the superficial strata of this squamous epithelium (x100).

	Discussion

Top ABSTRACT Introduction Materials and Methods Results Discussion REFERENCES

Deregulated signaling through the EGFR pathway is recognized to be an early event in the development of head and neck cancers (23) . Previously, we reported that EGF, a ligand of EGFR, induced COX-2 and PG synthesis in oral epithelial cells (24) . It is reasonable to postulate, therefore, that activation of the EGFR/Ras pathway contributes to the up-regulation of COX-2 in HNSCC. Additional studies are needed to confirm this mechanism.

Nonselective inhibitors of COX-1 and COX-2, such as piroxicam and indomethacin, prevent HNSCC in experimental animals (25) . Recently, selective inhibitors of COX-2 have been developed. These compounds possess anticancer properties (11 , 13) and appear to be safer than traditional nonsteroidal anti-inflammatory drugs. Based on the results of this study, it will be important to establish whether selective inhibitors of COX-2 are useful in preventing or treating HNSCC.

	FOOTNOTES

 
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by a grant from the Singapore Cancer Society.

² To whom requests for reprints should be addressed, at New York Presbyterian Hospital-Cornell Campus, Room F-231, 525 East 68th Street, New York, NY 10021. Phone: (212) 746-4403; Fax: (212) 746-8447; E-mail: ajdannen{at}mail.med.cornell.edu

³ The abbreviations used are: HNSCC, squamous cell carcinoma of the head and neck; COX-2, cyclooxygenase-2; PG, prostaglandin; RT-PCR, reverse transcription polymerase chain reaction; EGFR, epidermal growth factor receptor.

Received 12/15/98. Accepted 1/18/99.

	REFERENCES

Top ABSTRACT Introduction Materials and Methods Results Discussion REFERENCES

 

1. Landis S. H., Murray T., Bolen S., Wingo P. A. Cancer statistics, 1998. CA Cancer J. Clin., 48: 6-29, 1998.[Abstract]
2. Day G. L., Blot W. J. Second primary tumors in patients with oral cancer. Cancer (Phila.), 70: 14-19, 1992.[Medline]
3. Herschman H. R. Prostaglandin synthase 2. Biochim. Biophys. Acta., 1299: 125-140, 1996.[Medline]
4. Subbaramaiah K., Telang N., Ramonetti J. T., Araki R., DeVito B., Weksler B. B., Dannenberg A. J. Transcription of cyclooxygenase-2 is enhanced in transformed mammary epithelial cells. Cancer Res., 56: 4424-4429, 1996.[Abstract/Free Full Text]
5. Kelley D. J., Mestre J. R., Subbaramaiah K., Sacks P. G., Schantz S. P., Tanabe T., Inoue H., Ramonetti J. T., Dannenberg A. J. Benzo[a]pyrene up-regulates cyclooxygenase-2 gene expression in oral epithelial cells. Carcinogenesis (Lond.), 18: 795-799, 1997.[Abstract/Free Full Text]
6. Kutchera W., Jones D. A., Matsunami N., Groden J., McIntyre T. M., Zimmerman G. A., White R. L., Prescott S. M. Prostaglandin H synthase-2 is expressed abnormally in human colon cancer: evidence for a transcriptional effect. Proc. Natl. Acad. Sci. USA, 93: 4816-4820, 1996.[Abstract/Free Full Text]
7. Eberhart C. E., Coffey R. J., Radhika A., Giardiello F. M., Ferrenbach S., DuBois R. N. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology, 107: 1183-1188, 1994.[Medline]
8. Ristimaki A., Honkanen N., Jankala H., Sipponen P., Harkonen M. Expression of cyclooxygenase-2 in human gastric carcinoma. Cancer Res., 57: 1276-1280, 1997.[Abstract/Free Full Text]
9. Wilson K. T., Fu S., Ramanujam K. S., Meltzer S. J. Increased expression of inducible nitric oxide and cyclooxygenase-2 in Barrett’s esophagus and associated adenocarcinomas. Cancer Res., 58: 2929-2934, 1998.[Abstract/Free Full Text]
10. Hida T., Yatabe Y., Achiwa H., Muramatsu H., Kozaki K., Nakamura S., Ogawa M., Mitsudomi T., Sugiura T., Takahashi T. Increased expressed of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Res., 58: 3761-3764, 1998.[Abstract/Free Full Text]
11. Oshima M., Dinchuk J. E., Kargman S. L., Oshima H., Hancock B., Kwong E., Trzaskos J. M., Evans J. F., Taketo M. M. Suppression of intestinal polyposis in Apc⁷¹⁶ knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell, 87: 803-809, 1996.[Medline]
12. Tiano H., Chulada P., Spalding J., Lee C., Loftin C., Mahler J., Morham S., Langenbach R. Effects of cyclooxygenase deficiency on inflammation and papilloma development in mouse skin. Proc. Am. Assoc. Cancer Res., 38: 1727 1997.
13. Kawamori T., Rao C. V., Seibert K., Reddy B. S. Chemopreventive activity of Celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res., 58: 409-412, 1998.[Abstract/Free Full Text]
14. Karmali R. A., Wustrow T., Thaler H. T., Strong E. W. Prostaglandins in carcinomas of the head and neck. Cancer Lett., 22: 333-336, 1984.[Medline]
15. Jung T. T. K., Berlinger N. T., Juhn S. K. Prostaglandins in squamous cell carcinoma of the head and neck: a preliminary study. Laryngoscope, 95: 307-312, 1985.[Medline]
16. Sheng H., Shao J., Morrow J. D., Beauchamp R. D., DuBois R. N. Modulation of apoptosis and Bcl-2 expression by prostaglandin E₂ in human colon cancer cells. Cancer Res., 58: 362-366, 1998.[Abstract/Free Full Text]
17. Tsujii M., Kawano S., Tsuji S., Sawaoka H., Hori M., DuBois R. N. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell, 93: 705-716, 1998.[Medline]
18. Huang M., Stolina M., Sharma S., Mao J. T., Zhu L., Miller P. W., Wollman J., Herschman H., Dubinett S. M. Non-small cell lung cancer cyclooxygenase-2-dependent regulation of cytokine balance in lymphocytes and macrophages: up-regulation of interleukin 10 and down-regulation of interleukin 12 production. Cancer Res., 58: 1208-1216, 1998.[Abstract/Free Full Text]
19. Tsujii M., DuBois R. N. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell, 83: 493-501, 1995.[Medline]
20. Tsujii M., Kawano S., DuBois R. N. Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc. Natl. Acad. Sci. USA, 94: 3336-3340, 1997.[Abstract/Free Full Text]
21. Janot F., Massaad L., Ribrag V., de Waziers I., Beaune P. H., Luboinski B., Parise O., Gouyette A., Chabot G. G. Principal xenobiotic-metabolizing enzyme systems in human head and neck squamous cell carcinoma. Carcinogenesis (Lond.), 14: 1279-1283, 1993.[Abstract/Free Full Text]
22. Eling T. E., Thompson D. C., Foureman G. L., Curtis J. F., Hughes M. F. Prostaglandin H synthase and xenobiotic oxidation. Annu. Rev. Pharmacol. Toxicol., 30: 1-45, 1990.[Medline]
23. Shin D. M., Ro J. Y., Hong W. K., Hittelman W. N. Dysregulation of epidermal growth factor receptor expression in premalignant lesions during head and neck tumorigenesis. Cancer Res., 54: 3153-3159, 1994.[Abstract/Free Full Text]
24. Mestre J. R., Subbaramaiah K., Sacks P. G., Schantz S. P., Tanabe T., Inoue H., Dannenberg A. J. Retinoids suppress epidermal growth factor-induced transcription of cyclooxygenase-2 in human oral squamous carcinoma cells. Cancer Res., 57: 2890-2895, 1997.[Abstract/Free Full Text]
25. Tanaka T., Nishikawa A., Mori Y., Morishita Y., Mori H. Inhibitory effects of non-steroidal anti-inflammatory drugs, piroxicam and indomethacin on 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in male ACI/N rats. Cancer Lett., 48: 177-182, 1989.[Medline]

This article has been cited by other articles:

				V. D. Kekatpure, J. O. Boyle, X. K. Zhou, A. J. Duffield-Lillico, N. D. Gross, N. Y. Lee, K. Subbaramaiah, J. D. Morrow, G. Milne, S. M. Lippman, et al. Elevated Levels of Urinary Prostaglandin E Metabolite Indicate a Poor Prognosis in Ever Smoker Head and Neck Squamous Cell Carcinoma Patients Cancer Prevention Research, November 1, 2009; 2(11): 957 - 965. [Abstract] [Full Text] [PDF]

				E. S. Antonarakis, E. I. Heath, J. R. Walczak, W. G. Nelson, H. Fedor, A. M. De Marzo, M. L. Zahurak, S. Piantadosi, A. J. Dannenberg, R. T. Gurganus, et al. Phase II, Randomized, Placebo-Controlled Trial of Neoadjuvant Celecoxib in Men With Clinically Localized Prostate Cancer: Evaluation of Drug-Specific Biomarkers J. Clin. Oncol., October 20, 2009; 27(30): 4986 - 4993. [Abstract] [Full Text] [PDF]

				P. Arun, M. S. Brown, R. Ehsanian, Z. Chen, and C. Van Waes Nuclear NF-{kappa}B p65 Phosphorylation at Serine 276 by Protein Kinase A Contributes to the Malignant Phenotype of Head and Neck Cancer Clin. Cancer Res., October 1, 2009; 15(19): 5974 - 5984. [Abstract] [Full Text] [PDF]

				Role of Cyclooxygenase-2 in Tumor Progression and Survival of Head and Neck Squamous Cell Carcinoma Cancer Prevention Research, September 1, 2009; 2(9): 823 - 829.

				M. Sahin, E. Sahin, and S. Gumuslu Cyclooxygenase-2 in Cancer and Angiogenesis Angiology, April 1, 2009; 60(2): 242 - 253. [Abstract] [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]

				C. Husvik, C. Khuu, M. Bryne, and T.S. Halstensen PGE2 Production in Oral Cancer Cell Lines is COX-2-dependent Journal of Dental Research, February 1, 2009; 88(2): 164 - 169. [Abstract] [Full Text] [PDF]

				W. Zhang, N. Bhola, S. Kalyankrishna, W. Gooding, J. Hunt, R. Seethala, J. R. Grandis, and J. M. Siegfried Kinin B2 Receptor Mediates Induction of Cyclooxygenase-2 and Is Overexpressed in Head and Neck Squamous Cell Carcinomas Mol. Cancer Res., December 1, 2008; 6(12): 1946 - 1956. [Abstract] [Full Text] [PDF]

				A. Shibata, K. Nakagawa, P. Sookwong, T. Tsuduki, S. Tomita, H. Shirakawa, M. Komai, and T. Miyazawa Tocotrienol Inhibits Secretion of Angiogenic Factors from Human Colorectal Adenocarcinoma Cells by Suppressing Hypoxia-Inducible Factor-1{alpha} J. Nutr., November 1, 2008; 138(11): 2136 - 2142. [Abstract] [Full Text] [PDF]

				S. R. Mallery, J. C. Zwick, P. Pei, M. Tong, P. E. Larsen, B. S. Shumway, B. Lu, H. W. Fields, R. J. Mumper, and G. D. Stoner Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral Lesions Cancer Res., June 15, 2008; 68(12): 4945 - 4957. [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]

				S. Choi and J.N. Myers Molecular Pathogenesis of Oral Squamous Cell Carcinoma: Implications for Therapy Journal of Dental Research, January 1, 2008; 87(1): 14 - 32. [Abstract] [Full Text] [PDF]

				M. K. Sackett, I. Bairati, F. Meyer, E. Jobin, S. Lussier, A. Fortin, M. Gelinas, A. Nabid, F. Brochet, and B. Tetu Prognostic Significance of Cyclooxygenase-2 Overexpression in Glottic Cancer Clin. Cancer Res., January 1, 2008; 14(1): 67 - 73. [Abstract] [Full Text] [PDF]

				T. Onda, K. Uzawa, D. Nakashima, K. Saito, Y. Iwadate, N. Seki, T. Shibahara, and H. Tanzawa Lin-7C/VELI3/MALS-3: An Essential Component in Metastasis of Human Squamous Cell Carcinoma Cancer Res., October 15, 2007; 67(20): 9643 - 9648. [Abstract] [Full Text] [PDF]

				C. Bergmann, L. Strauss, R. Zeidler, S. Lang, and T. L. Whiteside Expansion of Human T Regulatory Type 1 Cells in the Microenvironment of Cyclooxygenase 2 Overexpressing Head and Neck Squamous Cell Carcinoma Cancer Res., September 15, 2007; 67(18): 8865 - 8873. [Abstract] [Full Text] [PDF]

				R. Benoliel, J. Epstein, E. Eliav, R. Jurevic, and S. Elad Orofacial Pain in Cancer: Part I--Mechanisms Journal of Dental Research, June 1, 2007; 86(6): 491 - 505. [Abstract] [Full Text] [PDF]

				P. Sinha, V. K. Clements, A. M. Fulton, and S. Ostrand-Rosenberg Prostaglandin E2 Promotes Tumor Progression by Inducing Myeloid-Derived Suppressor Cells Cancer Res., May 1, 2007; 67(9): 4507 - 4513. [Abstract] [Full Text] [PDF]

				J. M. Bock, S. G. Menon, L. L. Sinclair, N. S. Bedford, P. C. Goswami, F. E. Domann, and D. K. Trask Celecoxib Toxicity Is Cell Cycle Phase Specific Cancer Res., April 15, 2007; 67(8): 3801 - 3808. [Abstract] [Full Text] [PDF]

				E. I. Heath, M. I. Canto, S. Piantadosi, E. Montgomery, W. M. Weinstein, J. G. Herman, A. J. Dannenberg, V. W. Yang, A. O. Shar, E. Hawk, et al. Secondary Chemoprevention of Barrett's Esophagus With Celecoxib: Results of a Randomized Trial J Natl Cancer Inst, April 4, 2007; 99(7): 545 - 557. [Abstract] [Full Text] [PDF]

				H. Makita, M. Mutoh, T. Maruyama, K. Yonemoto, A. Kobayashi, H. Fujitsuka, M. Toida, T. Shibata, S. Miyamoto, Y. Yasui, et al. A prostaglandin E2 receptor subtype EP1-selective antagonist, ONO-8711, suppresses 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis Carcinogenesis, March 1, 2007; 28(3): 677 - 684. [Abstract] [Full Text] [PDF]

				X. Tong, R. T. Van Dross, A. Abu-Yousif, A. R. Morrison, and J. C. Pelling Apigenin Prevents UVB-Induced Cyclooxygenase 2 Expression: Coupled mRNA Stabilization and Translational Inhibition Mol. Cell. Biol., January 1, 2007; 27(1): 283 - 296. [Abstract] [Full Text] [PDF]

				A. Jimeno, M. L. Amador, P. Kulesza, X. Wang, B. Rubio-Viqueira, X. Zhang, A. Chan, J. Wheelhouse, H. Kuramochi, K. Tanaka, et al. Assessment of celecoxib pharmacodynamics in pancreatic cancer Mol. Cancer Ther., December 1, 2006; 5(12): 3240 - 3247. [Abstract] [Full Text] [PDF]

				V. Jayaprakash, N. R. Rigual, K. B. Moysich, T. R. Loree, M. A. S. Nasca, R. J. Menezes, and M. E. Reid Chemoprevention of head and neck cancer with aspirin: a case-control study. Arch Otolaryngol Head Neck Surg, November 1, 2006; 132(11): 1231 - 1236. [Abstract] [Full Text] [PDF]

				L. Y.Y. Fong, Y. Jiang, and J. L. Farber Zinc deficiency potentiates induction and progression of lingual and esophageal tumors in p53-deficient mice Carcinogenesis, July 1, 2006; 27(7): 1489 - 1496. [Abstract] [Full Text] [PDF]

				S. Grosch, T. J. Maier, S. Schiffmann, and G. Geisslinger Cyclooxygenase-2 (COX-2)-independent anticarcinogenic effects of selective COX-2 inhibitors. J Natl Cancer Inst, June 7, 2006; 98(11): 736 - 747. [Abstract] [Full Text] [PDF]

				S. M. Lippman and J. J. Lee Reducing the "Risk" of Chemoprevention: Defining and Targeting High Risk--2005 AACR Cancer Research and Prevention Foundation Award Lecture. Cancer Res., March 15, 2006; 66(6): 2893 - 2903. [Abstract] [Full Text] [PDF]

				T. Chen, H. Hwang, M. E. Rose, R. G. Nines, and G. D. Stoner Chemopreventive Properties of Black Raspberries in N-Nitrosomethylbenzylamine-Induced Rat Esophageal Tumorigenesis: Down-regulation of Cyclooxygenase-2, Inducible Nitric Oxide Synthase, and c-Jun. Cancer Res., March 1, 2006; 66(5): 2853 - 2859. [Abstract] [Full Text] [PDF]

				R. Suzuki, H. Kohno, M. Suzui, N. Yoshimi, H. Tsuda, K. Wakabayashi, and T. Tanaka An animal model for the rapid induction of tongue neoplasms in human c-Ha-ras proto-oncogene transgenic rats by 4-nitroquinoline 1-oxide: its potential use for preclinical chemoprevention studies Carcinogenesis, March 1, 2006; 27(3): 619 - 630. [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]

				H. Dalwadi, K. Krysan, N. Heuze-Vourc'h, M. Dohadwala, D. Elashoff, S. Sharma, N. Cacalano, A. Lichtenstein, and S. Dubinett Cyclooxygenase-2-Dependent Activation of Signal Transducer and Activator of Transcription 3 by Interleukin-6 in Non-Small Cell Lung Cancer Clin. Cancer Res., November 1, 2005; 11(21): 7674 - 7682. [Abstract] [Full Text] [PDF]

				C.-G. Liu, L. Zhang, Y. Jiang, D. Chatterjee, C. M. Croce, K. Huebner, and L. Y.Y. Fong Modulation of Gene Expression in Precancerous Rat Esophagus by Dietary Zinc Deficit and Replenishment Cancer Res., September 1, 2005; 65(17): 7790 - 7799. [Abstract] [Full Text] [PDF]

				R. Wu, A. L. Abramson, M. J. Shikowitz, A. J. Dannenberg, and B. M. Steinberg Epidermal Growth Factor-Induced Cyclooxygenase-2 Expression Is Mediated through Phosphatidylinositol-3 Kinase, Not Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase Kinase, in Recurrent Respiratory Papillomas Clin. Cancer Res., September 1, 2005; 11(17): 6155 - 6161. [Abstract] [Full Text] [PDF]

				X. Zhang, Z. Chen, M. S. Choe, Y. Lin, S.-Y. Sun, H. S. Wieand, H. J. C. Shin, A. Chen, F. R. Khuri, and D. M. Shin Tumor Growth Inhibition by Simultaneously Blocking Epidermal Growth Factor Receptor and Cyclooxygenase-2 in a Xenograft Model Clin. Cancer Res., September 1, 2005; 11(17): 6261 - 6269. [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]

				S. Sharma, L. Zhu, S. C. Yang, L. Zhang, J. Lin, S. Hillinger, B. Gardner, K. Reckamp, R. M. Strieter, M. Huang, et al. Cyclooxygenase 2 Inhibition Promotes IFN-{gamma}-Dependent Enhancement of Antitumor Responses J. Immunol., July 15, 2005; 175(2): 813 - 819. [Abstract] [Full Text] [PDF]

				H. Tanaka, T. Shirakawa, Z. Zhang, K. Hamada, A. Gotoh, and K.-i. Nibu A Replication-Selective Adenoviral Vector for Head and Neck Cancers Arch Otolaryngol Head Neck Surg, July 1, 2005; 131(7): 630 - 634. [Abstract] [Full Text] [PDF]

				N. K. Altorki, J. L. Port, F. Zhang, D. Golijanin, H. T. Thaler, A. J. Duffield-Lillico, K. Subbaramaiah, and A. J. Dannenberg Chemotherapy Induces the Expression of Cyclooxygenase-2 in Non-Small Cell Lung Cancer Clin. Cancer Res., June 1, 2005; 11(11): 4191 - 4197. [Abstract] [Full Text] [PDF]

				M. I. Patel, K. Subbaramaiah, B. Du, M. Chang, P. Yang, R. A. Newman, C. Cordon-Cardo, H. T. Thaler, and A. J. Dannenberg Celecoxib Inhibits Prostate Cancer Growth: Evidence of a Cyclooxygenase-2-Independent Mechanism Clin. Cancer Res., March 1, 2005; 11(5): 1999 - 2007. [Abstract] [Full Text] [PDF]

				D. Moraitis, B. Du, M. S. De Lorenzo, J. O. Boyle, B. B. Weksler, E. G. Cohen, J. F. Carew, N. K. Altorki, L. Kopelovich, K. Subbaramaiah, et al. Levels of Cyclooxygenase-2 Are Increased in the Oral Mucosa of Smokers: Evidence for the Role of Epidermal Growth Factor Receptor and Its Ligands Cancer Res., January 15, 2005; 65(2): 664 - 670. [Abstract] [Full Text] [PDF]

				A. J. Dannenberg, S. M. Lippman, J. R. Mann, K. Subbaramaiah, and R. N. DuBois Cyclooxygenase-2 and Epidermal Growth Factor Receptor: Pharmacologic Targets for Chemoprevention J. Clin. Oncol., January 10, 2005; 23(2): 254 - 266. [Abstract] [Full Text] [PDF]

				L. Y. Y. Fong, L. Zhang, Y. Jiang, and J. L. Farber Dietary Zinc Modulation of COX-2 Expression and Lingual and Esophageal Carcinogenesis in Rats J Natl Cancer Inst, January 5, 2005; 97(1): 40 - 50. [Abstract] [Full Text] [PDF]

				K. Krysan, H. Dalwadi, S. Sharma, M. Pold, and S. Dubinett Cyclooxygenase 2-Dependent Expression of Survivin Is Critical for Apoptosis Resistance in Non-Small Cell Lung Cancer Cancer Res., September 15, 2004; 64(18): 6359 - 6362. [Abstract] [Full Text] [PDF]

				Z. Chen, X. Zhang, M. Li, Z. Wang, H. S. Wieand, J. R. Grandis, and D. M. Shin Simultaneously Targeting Epidermal Growth Factor Receptor Tyrosine Kinase and Cyclooxygenase-2, an Efficient Approach to Inhibition of Squamous Cell Carcinoma of the Head and Neck Clin. Cancer Res., September 1, 2004; 10(17): 5930 - 5939. [Abstract] [Full Text] [PDF]

				Y.-K. Won, C.-N. Ong, X. Shi, and H.-M. Shen Chemopreventive activity of parthenolide against UVB-induced skin cancer and its mechanisms Carcinogenesis, August 1, 2004; 25(8): 1449 - 1458. [Abstract] [Full Text] [PDF]

				R. C.K. Panguluri, L. O. Long, W. Chen, S. Wang, A. Coulibaly, F. Ukoli, A. Jackson, S. Weinrich, C. Ahaghotu, W. Isaacs, et al. COX-2 gene promoter haplotypes and prostate cancer risk Carcinogenesis, June 1, 2004; 25(6): 961 - 966. [Abstract] [Full Text] [PDF]

				H. E. Zeytin, A. C. Patel, C. J. Rogers, D. Canter, S. D. Hursting, J. Schlom, and J. W. Greiner Combination of a Poxvirus-Based Vaccine with a Cyclooxygenase-2 Inhibitor (Celecoxib) Elicits Antitumor Immunity and Long-Term Survival in CEA.Tg/MIN Mice Cancer Res., May 15, 2004; 64(10): 3668 - 3678. [Abstract] [Full Text] [PDF]

				P. Nix, M. Lind, J. Greenman, N. Stafford, and L. Cawkwell Expression of Cox-2 protein in radioresistant laryngeal cancer Ann. Onc., May 1, 2004; 15(5): 797 - 801. [Abstract] [Full Text] [PDF]

				J.-L. Roh, M.-W. Sung, S.-W. Park, D.-S. Heo, D. W. Lee, and K. H. Kim Celecoxib Can Prevent Tumor Growth and Distant Metastasis in Postoperative Setting Cancer Res., May 1, 2004; 64(9): 3230 - 3235. [Abstract] [Full Text] [PDF]

				T. Almahmeed, J. O. Boyle, E. G. Cohen, J. F. Carew, B. Du, N. K. Altorki, L. Kopelovich, J.-L. Fang, P. Lazarus, K. Subbaramaiah, et al. Benzo[a]pyrene phenols are more potent inducers of CYP1A1, CYP1B1 and COX-2 than benzo[a]pyrene glucuronides in cell lines derived from the human aerodigestive tract Carcinogenesis, May 1, 2004; 25(5): 793 - 799. [Full Text] [PDF]

				S. Lanza-Jacoby, A. P. Dicker, S. Miller, F. E. Rosato, J. T. Flynn, S. N. Lavorgna, and R. Burd Cyclooxygenase (COX)-2-dependent effects of the inhibitor SC236 when combined with ionizing radiation in mammary tumor cells derived from HER-2/neu mice Mol. Cancer Ther., April 1, 2004; 3(4): 417 - 424. [Abstract] [Full Text] [PDF]

				J. P. Russell, J. B. Engiles, and J. L. Rothstein Proinflammatory Mediators and Genetic Background in Oncogene Mediated Tumor Progression J. Immunol., April 1, 2004; 172(7): 4059 - 4067. [Abstract] [Full Text] [PDF]

				D. Wei, L. Wang, Y. He, H. Q. Xiong, J. L. Abbruzzese, and K. Xie Celecoxib Inhibits Vascular Endothelial Growth Factor Expression in and Reduces Angiogenesis and Metastasis of Human Pancreatic Cancer via Suppression of Sp1 Transcription Factor Activity Cancer Res., March 15, 2004; 64(6): 2030 - 2038. [Abstract] [Full Text] [PDF]

				K. Temma, K. Shimoya, Q. Zhang, T. Kimura, K. Wasada, T. Kanzaki, C. Azuma, M. Koyama, and Y. Murata Effects of 4-hydroxy-2-nonenal, a marker of oxidative stress, on the cyclooxygenase-2 of human placenta in chorioamnionitis Mol. Hum. Reprod., March 1, 2004; 10(3): 167 - 171. [Abstract] [Full Text] [PDF]

				B. W. Chang, D. H. Kim, D. P. Kowalski, J. A. Burleson, Y. H. Son, L. D. Wilson, and B. G. Haffty Prognostic Significance of Cyclooxygenase-2 in Oropharyngeal Squamous Cell Carcinoma Clin. Cancer Res., March 1, 2004; 10(5): 1678 - 1684. [Abstract] [Full Text] [PDF]

				S. K. Kulp, Y.-T. Yang, C.-C. Hung, K.-F. Chen, J.-P. Lai, P.-H. Tseng, J. W. Fowble, P. J. Ward, and C.-S. Chen 3-Phosphoinositide-Dependent Protein Kinase-1/Akt Signaling Represents a Major Cyclooxygenase-2-Independent Target for Celecoxib in Prostate Cancer Cells Cancer Res., February 15, 2004; 64(4): 1444 - 1451. [Abstract] [Full Text] [PDF]

				G. E. Kim, Y. B. Kim, N. H. Cho, H.-C. Chung, H. R. Pyo, J. D. Lee, T. K. Park, W. S. Koom, M. Chun, and C. O. Suh Synchronous Coexpression of Epidermal Growth Factor Receptor and Cyclooxygenase-2 in Carcinomas of the Uterine Cervix: A Potential Predictor of Poor Survival Clin. Cancer Res., February 15, 2004; 10(4): 1366 - 1374. [Abstract] [Full Text] [PDF]

				M. S. Shaik, A. Chatterjee, and M. Singh Effect of a Selective Cyclooxygenase-2 Inhibitor, Nimesulide, on the Growth of Lung Tumors and Their Expression of Cyclooxygenase-2 and Peroxisome Proliferator- Activated Receptor-{gamma} Clin. Cancer Res., February 15, 2004; 10(4): 1521 - 1529. [Abstract] [Full Text] [PDF]

				D. Golijanin, J.-Y. Tan, A. Kazior, E. G. Cohen, P. Russo, G. Dalbagni, K. J. Auborn, K. Subbaramaiah, and A. J. Dannenberg Cyclooxygenase-2 and Microsomal Prostaglandin E Synthase-1 Are Overexpressed in Squamous Cell Carcinoma of the Penis Clin. Cancer Res., February 1, 2004; 10(3): 1024 - 1031. [Abstract] [Full Text] [PDF]

				S. Lanza-Jacoby, S. Miller, J. Flynn, K. Gallatig, C. Daskalakis, J. L. Masferrer, B. S. Zweifel, H. Sembhi, and I. H. Russo The Cyclooxygenase-2 Inhibitor, Celecoxib, Prevents the Development of Mammary Tumors in HER-2/neu Mice Cancer Epidemiol. Biomarkers Prev., December 1, 2003; 12(12): 1486 - 1491. [Abstract] [Full Text] [PDF]

				M. ROMANO and J. CLARIA Cyclooxygenase-2 and 5-lipoxygenase converging functions on cell proliferation and tumor angiogenesis: implications for cancer therapy FASEB J, November 1, 2003; 17(14): 1986 - 1995. [Abstract] [Full Text] [PDF]

				M. S. De Lorenzo, K. Yamaguchi, K. Subbaramaiah, and A. J. Dannenberg Bryostatin-1 Stimulates the Transcription of Cyclooxygenase-2: Evidence for an Activator Protein-1-Dependent Mechanism Clin. Cancer Res., October 15, 2003; 9(13): 5036 - 5043. [Abstract] [Full Text] [PDF]

				H. Choy and L. Milas Enhancing Radiotherapy With Cyclooxygenase-2 Enzyme Inhibitors: A Rational Advance? J Natl Cancer Inst, October 1, 2003; 95(19): 1440 - 1452. [Abstract] [Full Text] [PDF]

				Q.-T. Le and A. J. Giaccia Therapeutic Exploitation of the Physiological and Molecular Genetic Alterations in Head and Neck Cancer Clin. Cancer Res., October 1, 2003; 9(12): 4287 - 4295. [Abstract] [Full Text] [PDF]

				K. Subbaramaiah, T. P. Marmo, D. A. Dixon, and A. J. Dannenberg Regulation of Cyclooxgenase-2 mRNA Stability by Taxanes: EVIDENCE FOR INVOLVEMENT OF p38, MAPKAPK-2, and HuR J. Biol. Chem., September 26, 2003; 278(39): 37637 - 37647. [Abstract] [Full Text] [PDF]

				K.-T. Kuo, K.-C. Chow, Y.-C. Wu, C.-S. Lin, H.-W. Wang, W.-Y. Li, and L.-S. Wang Clinicopathologic significance of cyclooxygenase-2 overexpression in esophageal squamous cell carcinoma Ann. Thorac. Surg., September 1, 2003; 76(3): 909 - 914. [Abstract] [Full Text] [PDF]

				P. K. Ha and J. A. Califano THE MOLECULAR BIOLOGY OF MUCOSAL FIELD CANCERIZATION OF THE HEAD AND NECK Critical Reviews in Oral Biology & Medicine, September 1, 2003; 14(5): 363 - 369. [Abstract] [Full Text] [PDF]

				E. G. Cohen, T. Almahmeed, B. Du, D. Golijanin, J. O. Boyle, R. A. Soslow, K. Subbaramaiah, and A. J. Dannenberg Microsomal Prostaglandin E Synthase-1 Is Overexpressed in Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., August 1, 2003; 9(9): 3425 - 3430. [Abstract] [Full Text] [PDF]

				J.-H. Jeng, Y.-J. Wang, B.-L. Chiang, P.-H. Lee, C.-P. Chan, Y.-S. Ho, T.-M. Wang, J.-J. Lee, L.-J. Hahn, and M.-C. Chang Roles of keratinocyte inflammation in oral cancer: regulating the prostaglandin E2, interleukin-6 and TNF-{alpha} production of oral epithelial cells by areca nut extract and arecoline Carcinogenesis, August 1, 2003; 24(8): 1301 - 1315. [Abstract] [Full Text] [PDF]

				D. Y. Zhang, J. Wu, F. Ye, L. Xue, S. Jiang, J. Yi, W. Zhang, H. Wei, M. Sung, W. Wang, et al. Inhibition of Cancer Cell Proliferation and Prostaglandin E2 Synthesis by Scutellaria Baicalensis Cancer Res., July 15, 2003; 63(14): 4037 - 4043. [Abstract] [Full Text] [PDF]

				N.K. Altorki, R.S. Keresztes, J.L. Port, D.M. Libby, R.J. Korst, D.B. Flieder, C.A. Ferrara, D.F. Yankelevitz, K. Subbaramaiah, M.W. Pasmantier, et al. Celecoxib, a Selective Cyclo-Oxygenase-2 Inhibitor, Enhances the Response to Preoperative Paclitaxel and Carboplatin in Early-Stage Non-Small-Cell Lung Cancer J. Clin. Oncol., July 15, 2003; 21(14): 2645 - 2650. [Abstract] [Full Text] [PDF]

				F. ZHANG, S. P. ENGEBRETSON, R. S. MORTON, P. F. CAVANAUGH JR., K. SUBBARAMAIAH, and A. J. DANNENBERG The overexpression of cyclo-oxygenase-2 in chronic periodontitis J Am Dent Assoc, July 1, 2003; 134(7): 861 - 867. [Abstract] [Full Text] [PDF]

				H. A. Minter, J. W. Eveson, S. Huntley, D. J. E. Elder, and A. Hague The Cyclooxygenase 2-selective Inhibitor NS398 Inhibits Proliferation of Oral Carcinoma Cell Lines by Mechanisms Dependent and Independent of Reduced Prostaglandin E2 Synthesis Clin. Cancer Res., May 1, 2003; 9(5): 1885 - 1897. [Abstract] [Full Text] [PDF]

				M. Dohadwala, R. K. Batra, J. Luo, Y. Lin, K. Krysan, M. Pold, S. Sharma, and S. M. Dubinett Autocrine/Paracrine Prostaglandin E2 Production by Non-small Cell Lung Cancer Cells Regulates Matrix Metalloproteinase-2 and CD44 in Cyclooxygenase-2-dependent Invasion J. Biol. Chem., December 20, 2002; 277(52): 50828 - 50833. [Abstract] [Full Text] [PDF]

				M. A. C. Sabino, J. R. Ghilardi, J. L. M. Jongen, C. P. Keyser, N. M. Luger, D. B. Mach, C. M. Peters, S. D. Rogers, M. J. Schwei, C. de Felipe, et al. Simultaneous Reduction in Cancer Pain, Bone Destruction, and Tumor Growth by Selective Inhibition of Cyclooxygenase-2 Cancer Res., December 15, 2002; 62(24): 7343 - 7349. [Abstract] [Full Text] [PDF]

				A. G. Banerjee, V. K. Gopalakrishnan, I. Bhattacharya, and J. K. Vishwanatha Deregulated Cyclooxygenase-2 Expression in Oral Premalignant Tissues Mol. Cancer Ther., December 1, 2002; 1(14): 1265 - 1271. [Abstract] [Full Text] [PDF]

				B. S. Zweifel, T. W. Davis, R. L. Ornberg, and J. L. Masferrer Direct Evidence for a Role of Cyclooxygenase 2-derived Prostaglandin E2 in Human Head and Neck Xenograft Tumors Cancer Res., November 15, 2002; 62(22): 6706 - 6711. [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]

				C Costa, R Soares, J S Reis-Filho, D Leitao, I Amendoeira, and F C Schmitt Cyclo-oxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer J. Clin. Pathol., June 1, 2002; 55(6): 429 - 434. [Abstract] [Full Text] [PDF]

				K. Subbaramaiah, L. Norton, W. Gerald, and A. J. Dannenberg Cyclooxygenase-2 Is Overexpressed in HER-2/neu-positive Breast Cancer. EVIDENCE FOR INVOLVEMENT OF AP-1 AND PEA3 J. Biol. Chem., May 17, 2002; 277(21): 18649 - 18657. [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]

				K. Subbaramaiah, P. A. Cole, and A. J. Dannenberg Retinoids and Carnosol Suppress Cyclooxygenase-2 Transcription by CREB-binding Protein/p300-dependent and -independent Mechanisms Cancer Res., May 1, 2002; 62(9): 2522 - 2530. [Abstract] [Full Text] [PDF]

				J. M. Wallace Nutritional and Botanical Modulation of the Inflammatory Cascade--Eicosanoids, Cyclooxygenases, and Lipoxygenases-- As an Adjunct in Cancer Therapy Integr Cancer Ther, March 1, 2002; 1(1): 7 - 37. [Abstract] [PDF]

				C. Denkert, M. Kobel, S. Pest, I. Koch, S. Berger, M. Schwabe, A. Siegert, A. Reles, B. Klosterhalfen, and S. Hauptmann Expression of Cyclooxygenase 2 Is an Independent Prognostic Factor in Human Ovarian Carcinoma Am. J. Pathol., March 1, 2002; 160(3): 893 - 903. [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]

				A. Denda, W. Kitayama, A. Murata, H. Kishida, Y. Sasaki, O. Kusuoka, T. Tsujiuchi, M. Tsutsumi, D. Nakae, H. Takagi, et al. Increased expression of cyclooxygenase-2 protein during rat hepatocarcinogenesis caused by a choline-deficient, L-amino acid-defined diet and chemopreventive efficacy of a specific inhibitor, nimesulide Carcinogenesis, February 1, 2002; 23(2): 245 - 256. [Abstract] [Full Text] [PDF]

				V. de Ledinghen, H. Liu, F. Zhang, C. R. Lo, K. Subbaramaiah, A. J. Dannenberg, and M. J. Czaja Induction of cyclooxygenase-2 by tumor promoters in transformed and cytochrome P450 2E1-expressing hepatocytes Carcinogenesis, January 1, 2002; 23(1): 73 - 79. [Abstract] [Full Text] [PDF]

				Y. Cao, K. B. Dave, T. P. Doan, and S. M. Prescott Fatty Acid CoA Ligase 4 Is Up-Regulated in Colon Adenocarcinoma Cancer Res., December 1, 2001; 61(23): 8429 - 8434. [Abstract] [Full Text] [PDF]

				K. Yoshimatsu, D. Golijanin, P. B. Paty, R. A. Soslow, P.-J. Jakobsson, R. A. DeLellis, K. Subbaramaiah, and A. J. Dannenberg Inducible Microsomal Prostaglandin E Synthase Is Overexpressed in Colorectal Adenomas and Cancer Clin. Cancer Res., December 1, 2001; 7(12): 3971 - 3976. [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]

				A. Onn, J. E. Tseng, and R. S. Herbst Thalidomide, Cyclooxygenase-2, and Angiogenesis: Potential for Therapy Clin. Cancer Res., November 1, 2001; 7(11): 3311 - 3313. [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]

				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]

				E. C. Jaeckel, S. Raja, J. Tan, S. K. Das, S. K. Dey, D. A. Girod, T. T. Tsue, and T. R. Sanford Correlation of Expression of Cyclooxygenase-2, Vascular Endothelial Growth Factor, and Peroxisome Proliferator-Activated Receptor {delta} With Head and Neck Squamous Cell Carcinoma Arch Otolaryngol Head Neck Surg, October 1, 2001; 127(10): 1253 - 1259. [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]

				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]

				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]

				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]

This Article Abstract 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 Chan, G. Articles by Dannenberg, A. J. Search for Related Content PubMed PubMed Citation Articles by Chan, G. Articles by Dannenberg, A. J.