Expression of Cyclooxygenase-2 in Human Transitional Cell Carcinoma of the Urinary Bladder

Abstract

Recent studies suggest that expression of cyclooxygenase-2 (Cox-2) is elevated in transitional cell carcinoma (TCC) of the urinary bladder and that inhibition of Cox-2 activity suppresses bladder cancer in experimental animal models. We have investigated the expression of Cox-2 protein in human TCCs (n = 85), in in situ carcinomas (Tis) of the urinary bladder (n = 17), and in nonneoplastic urinary bladder samples (n = 16) using immunohistochemistry. Cox-2 immunoreactivity was detected in 66% (67 of 102) of the carcinomas, whereas only 25% (4 of 16) of the nonneoplastic samples were positive (P: < 0.005). Cox-2 immunoreactivity localized to neoplastic cells in the carcinoma samples. The rate of positivity was the same in invasive (T1-3; 70%, n = 40) and in noninvasive (Tis and Ta; 65%, n = 62) carcinomas, but noninvasive tumors had a higher frequency (32%) of homogenous pattern of staining (>90% of the tumor cells positive) than the invasive carcinomas (10%) (P: < 0.05). However, several invasive TCCs exhibited the strongest intensity of Cox-2 staining in the invading cells, whereas other parts of the tumor were virtually negative. Finally, strong Cox-2 positivity was also found in nonneoplastic ulcerations (2 of 2) and in inflammatory pseudotumors (2 of 2), in which the immunoreactivity localized to the nonepithelial cells. Taken together, our data suggest that Cox-2 is highly expressed in noninvasive bladder carcinomas, whereas the highest expression of invasive tumors associated with the invading cells, and that Cox-2 may also have a pathophysiological role in nonneoplastic conditions of the urinary bladder, such as ulcerations and inflammatory pseudotumors.

Mn‐SOD antisense upregulates in vivo apoptosis of squamous cell carcinoma cells by anticancer drugs and γ‐rays regulating expression of the BCL‐2 family proteins, COX‐2 and p21

“…[45][46][47] Although one study reported that COX-2 expression was positively correlated with ROI production and decreased by antioxidants, 48,49 the present study indicated that COX-2 expression was decreased by Mn-SOD antisense in correlation with Bcl-2 expression. The mechanism of the decrease of COX-2 expression is not clear, but high levels of NO have been reported to suppress COX-2 expression.…”

Cyclooxygenase‐2 expression in human pituitary tumors

“…10,38 Although the potential therapeutic efficacy of NSAIDs was related exclusively to tumors located in the digestive tract, some studies have suggested that COX-2 may be the target for the prevention and treatment of other carcinomas, including those of the prostate, 8,39 breast, 13,40,41 pancreas, 12,42 head and neck, 43 and the urinary bladder. 44,45 To our knowledge, no epidemiologic studies have been performed to determine the protective effects of COX-2 inhibitors on the development and progression of pituitary tumors. Our observations of higher COX-2 expression in pituitary tumor specimens compared with normal tissue specimens are consistent with previous findings reporting COX-2 overexpression in tumor specimens.…”

Enhanced inhibitive effects of combination of rofecoxib and octreotide on the growth of human gastric cancer

“…Accumulative evidence has shown that overexpression of cyclooxygenase-2 (COX-2) in gastric adenocarcinoma might play a crucial role in invasive tumor growth and offer a new strategy against cancer by the use of COX-2 inhibitors. [1][2][3][4] The inhibitive effect of aspirin or rofecoxib, a higher selective COX-2 inhibitor 5 on the proliferation of gastric cancer, has been observed in our previous studies. 6,7 Various studies have demonstrated that the growth of normal cells and malignant tumor may be regulated by gut peptides.…”

“…Interaction of the 2 drugs is quantitatively determined by the combination index (CI), which is calculated as follows: 2 , where D X is the dose that is required to produce X% inhibition of 3 H-TdR incorporation. When CI ϭ 1, summation is indicated; when CI Ͻ 1, synergism is indicated; when CI Ͼ 1, antagonism is indicated.…”