Role Of Cyclooxygenase-2 In Carcinogenesis Research Articles

Cyclooxygenase-2 (COX-2) Expression in Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma: An Immunohistochemical Study.

Introduction:Growing evidence has shown that cyclooxygenase-2 (COX-2), an enzyme capable of catalyzing prostaglandin production, plays a key role in carcinogenesis. Selective COX-2 inhibitors have been shown to reduce the establishment of tumors such as oral squamous cell carcinoma (OSCC) and premalignant conditions such oral submucous fibrosis (OSMF) in experimental models. The aim of this study was to investigate the immunohistochemical expression of COX-2 in OSCC and OSMF with the normal oral mucosa as control.Material and Methods:Forty-five formalin-fixed paraffin-embedded samples comprising 20 OSCC, 20 OSMF, and 5 normal oral mucosa specimens were withdrawn from the archives of the Department of Oral and Maxillofacial Pathology for immunohistochemical examination for COX-2 expression. Negative and less than 5% COX-2 positivity was considered negative expressions, while greater than or equal to 5% COX-2 positivity was considered positive expression. The data obtained were statistically analyzed.Results:The difference in percentages of expression in normal mucosa, OSCC, and OSMF was highly significant (P < 0.01). In comparison to normal mucosa, OSCC and OSMF had an increased level of COX-2 expression. However, there was an insignificant difference between the various histological gradings of OSCC and OSMF.Conclusion:The results of the present study confirm the role of COX-2 in carcinogenesis and in the progression of premalignant conditions to malignancy.

The Effect of Cyclooxygenase-2 Expression in Uterine Carcinosarcoma on Survival

To reassess the effect cyclooxygenase-2 (COX-2) expression in carcinosarcoma on survival based on mature 5-year survival data. A comparison of 5-year survival of 27 patients with carcinosarcoma according to the presence of COX-2 immunohistochemical staining and staining score was performed. The 5-year survival of those with positive and negative COX-2 staining was statistically not different. However, there was a clear trend for more favorable 5-year survival in patients with a high staining score than in those with a low score, and the difference was of borderline significance (38.5% vs 7.1%; P = 0.06). In view of the role of COX-2 in carcinogenesis, our finding that COX-2 expression may confer a better survival in patients with carcinosarcoma is intriguing. Larger studies are indicated to elucidate the effect of COX-2 expression on survival in patients with carcinosarcoma because this may have therapeutic implications.

Cyclo-oxygenase-2 expression in oral squamous cell carcinoma.

Many evidences showed that cyclooxygenase-2 (COX-2), an enzyme that catalyzes the synthesis of prostaglandins, has an important role in carcinogenesis. It has been observed in experimental models that selective COX-2 inhibitors suppress the formation of tumors including tongue carcinoma. The aim of this study was to investigate the immunohistochemical expression of COX-2 in oral squamous cell carcinoma (OSCC) compared to normal oral mucosa and oral dysplasia. A total of 60 paraffined blocks (20 cases of OSCC, 20 cases of oral epithelial dysplasia and 20 cases of normal oral mucosa were included in this study and immunohistochemical staining was done for COX-2 expression. From each sample, 5 high power fields were assessed to determine the percentage of stained cells and staining intensity. Immunoreactivity was obtained by multiplying the above two cases. Data were analyzed with using the Kruskal-Wallis test ANOVA, Mann-Whitney test and least significant difference and P<0.05 was declared as significant. High level of COX-2 expression was found in OSCC and dysplasia compared to normal mucosa. Furthermore, a positive correlation was found between COX-2 expression and severity of dysplasia. However, no significant difference between low grade and high grade tumors was found. The result of the present study supports from the role of COX-2 in carcinogenesis and progression of premalignant lesion to malignancy.

Cyclooxygenase-2 (COX-2) in Carcinogenesis and Selective COX-2 Inhibitors for Chemoprevention in Gastrointestinal Cancers

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to have a property to inhibit tumor development in some cancers while it shows various side effects such as gastrointestinal bleeding and renal disorder. Selective cyclooxygenase (COX)-2 inhibitors (coxibs) were originally developed as one of anti-inflammatory drugs to avoid side effect of NSAIDs. Fortunately, the coxibs was also proved to have an inhibiting effect on tumorigenesis by many experimental studies using cell lines and animal models like NSAIDs. Since a randomized study for polyp chemoprevention by celecoxib in familial adenomatous polyposis (FAP) patients demonstrated a significant reduction in the number of colorectal polyps, the clinical use of celecoxib was approved for FAP patients. Three large trials using celecoxib (the Adenoma Prevention with Celebrex and the Prevention of Spontaneous Adenomatopus Polyps) or refecoxib (the Adenomatous Polyp Prevention on Vioxx) for the recurrence of colorectal polyps in patients with a history of colorectal adenoma polypectomized confirmed chemopreventive effects on colorectal adenoma but two of three trails alerted us a hazard of cardiovascular (CV) events. Thereafter, some coxibs were withdrawn from the market because they showed to increase risk of serious CV events including heart attacks and strokes. But recent reports concluded that a merit of the reduction in gastrointestinal events by coxibs exceeded a demerit of the increase in serious CV events. In this review, a role of COX-2 in carcinogenesis of gastrointestinal tract and a future of coxibs for chemoprevention are discussed.

Role of COX-2 in carcinogenesis of colorectal cancer and its relationship with tumor biological characteristics and patients' prognosis.

Recent clinical epidemiological studies have demonstrated the preventive effect of non-steroidal anti-inflammatory drugs (NSAIDs) against colorectal cancer. The underlying mechanism might be the inhibition of rate-limiting enzyme cyclooxygenase-2 (COX-2) in metabolism of arachidonic acid. The role of COX-2 in carcinogenesis of colorectal cancer and its relationship with tumor biological characteristics and patients' prognosis still remain unclear. This study was to investigate the role of COX-2 expression in carcinogenesis of colorectal cancer and its relationship with tumor biological characteristics and patients' prognosis. A total of 139 colorectal cancers and 19 adenomas surgically treated in School of Oncology, Peking University, from January 1993 to September 2001 were retrospectively studied. COX-2 expression was detected with tissue microarray (TMA) and immunohistochemistry (IHC) procedure. The association between COX-2 expression and clinicopathological features and its influence on patients' prognosis were studied. COX-2 expression was strong in colorectal cancer, moderate in adenoma and weak in normal mucosa, which demonstrated statistically significant difference (chi(2)=46.997, P<0.001). COX-2 expression had no association with clinicopathological features such as gross type, differentiation, invasion depth, vessel emboli and TNM staging. Cox proportional hazards modeling analysis and Log rank test revealed no prognostic role of COX-2 expression in colorectal cancer patients. COX-2 may play an important role in the early stage of carcinogenesis, and its expression in colorectal cancer is not associated with clinicopathological features and patients' prognosis.