BACKGROUND/AIMS: To investigate the degree of cyclooxygenase-2 (COX-2) protein expression in chronic hepatitis and cirrhosis. METHODS: COX-2 protein expression was evaluated in 43 cases of chronic hepatitis and 24 cases of cirrhosis using immunohistochemical techniques. The COX-2 immunohistochemical staining score was assessed using the scoring systems of Pazirandeh et al and Qiu et al. and each scoring system was based on a sum of the parameters of staining intensity and distribution. RESULTS: The mean COX-2 expression scores in chronic hepatitis and cirrhosis were 2.5 +/- 1.3 vs. 3.3 +/- 1.1 (p = 0.008), and 3.2 +/- 2.0 vs. 4.5 +/- 1.7 (p = 0.006), respectively, based on the Pazirandeh et al. and Qiu et al. scoring systems. The percentage samples of high COX-2 expression score (4 to 5) in chronic hepatitis and cirrhosis were 16.3% vs. 45.8% (p = 0.022), and 23.3% vs. 50% (p = 0.021), respectively, based on the two scoring systems. The mean COX-2 expression scores based on the severity of hepatic fibrosis scored using Ishak's modified staging system (fibrosis score 0 to 3 vs. 4 to 6) were 2.4 +/- 1.3 vs. 3.2 +/- 1.1 (p = 0.009), and 3.1 +/- 2.0 vs. 4.3 +/- 1.8 (p = 0.009), respectively, based on the two scoring systems. CONCLUSIONS: COX-2 expression was significantly higher in liver cirrhosis group than in chronic hepatitis. COX-2 expression scores according to Ishak's staging was significantly higher in the advanced fibrosis group. COX-2 may play a role in the progression of hepatic fibrosis.
Adult ; Aged ; Cyclooxygenase 2/analysis/*physiology ; Cyclooxygenase 2 Inhibitors/therapeutic use ; Disease Progression ; Female ; Hepatitis, Chronic/enzymology ; Humans ; Immunohistochemistry ; Liver Cirrhosis/drug therapy/*enzymology ; Male ; Middle Aged

PURPOSE: This study was undertaken to evaluate the significance of cyclooxygenase-2 (COX2) overexpression and the expression of somatostatin receptor (SSTR) subtypes in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). MATERIALS AND METHODS: Two hundred and forty-seven cases of GEP-NET, comprising 86 foregut and 156 hindgut primary NETs, and 5 metastatic NETs in the liver, were studied retrospectively with immunohistochemistry for COX2, chromogranin A, Ki-67, SSTR1, SSTR2, and SSTR5. RESULTS: COX2 overexpression was observed in 54%(126 of 234), and SSTR1, SSTR2, and SSTR5 positivity in 84%(196 of 233), 72%(168 of 233), and 55%(128 of 232), respectively. COX2 overexpression was found to be positively correlated with Ki-67 labeling index and inversely correlated with the expression of SSTR subtypes. In addition, the expression of SSTR subtypes was tightly correlated in any comparative pairs. A significant inverse correlation was found between COX2 and SSTR2 expression in the foregut, but not hindgut NETs. Kaplan-Meier analyses showed that COX2 overexpression (p=0.003) and high Ki-67 labeling index (p<0.001) were associated with poor overall survival (OS), whereas expression of SSTR2 (p<0.001) was associated with better OS of GEP-NET patients. Multivariate analysis revealed negative SSTR2 expression as an independent prognostic marker in GEP-NET patients (p<0.001). CONCLUSION: Our results suggest that expression of SSTR subtypes is associated with favorable prognosis, whereas COX2 overexpression is associated with poor prognosis in GEP-NETs. Taken together, COX2 could be a possible therapeutic target in some subsets of GEP-NETs.
Chromogranin A ; Cyclooxygenase 2 ; Humans ; Immunohistochemistry ; Liver ; Multivariate Analysis ; Neuroendocrine Tumors ; Prognosis ; Receptors, Somatostatin ; Retrospective Studies ; Somatostatin

PURPOSE: This study was undertaken to evaluate the significance of cyclooxygenase-2 (COX2) overexpression and the expression of somatostatin receptor (SSTR) subtypes in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). MATERIALS AND METHODS: Two hundred and forty-seven cases of GEP-NET, comprising 86 foregut and 156 hindgut primary NETs, and 5 metastatic NETs in the liver, were studied retrospectively with immunohistochemistry for COX2, chromogranin A, Ki-67, SSTR1, SSTR2, and SSTR5. RESULTS: COX2 overexpression was observed in 54%(126 of 234), and SSTR1, SSTR2, and SSTR5 positivity in 84%(196 of 233), 72%(168 of 233), and 55%(128 of 232), respectively. COX2 overexpression was found to be positively correlated with Ki-67 labeling index and inversely correlated with the expression of SSTR subtypes. In addition, the expression of SSTR subtypes was tightly correlated in any comparative pairs. A significant inverse correlation was found between COX2 and SSTR2 expression in the foregut, but not hindgut NETs. Kaplan-Meier analyses showed that COX2 overexpression (p=0.003) and high Ki-67 labeling index (p<0.001) were associated with poor overall survival (OS), whereas expression of SSTR2 (p<0.001) was associated with better OS of GEP-NET patients. Multivariate analysis revealed negative SSTR2 expression as an independent prognostic marker in GEP-NET patients (p<0.001). CONCLUSION: Our results suggest that expression of SSTR subtypes is associated with favorable prognosis, whereas COX2 overexpression is associated with poor prognosis in GEP-NETs. Taken together, COX2 could be a possible therapeutic target in some subsets of GEP-NETs.
Chromogranin A ; Cyclooxygenase 2 ; Humans ; Immunohistochemistry ; Liver ; Multivariate Analysis ; Neuroendocrine Tumors ; Prognosis ; Receptors, Somatostatin ; Retrospective Studies ; Somatostatin

PURPOSE: Epidemiologic studies have indicated that the use of nonsteroidal anti-inflammatory drugs, which inhibit cyclooxygenase activity, reduce the risk of colorectal cancer. In addition, several studies have demonstrated the increased expression of cyclooxygenase-2 (COX-2) in human colorectal cancer tissues. However, the role of COX-2 in colorectal cancer has not been fully established. The aim of this study was to clarify the clinicopathologic significance of COX-2 expression in human colorectal cancer. METHODS: We performed immunohistochemical straining for COX-2 expression in 124 human colorectal cancer specimens. COX-2 expression was then compared with clinicopathologic factors and survival outcomes. RESULTS: COX-2 was expressed in the cytoplasm of the cancer cells. COX-2 expression was noted in 86.3% of the cancer patients and significantly correlated with the histologic type. The depth of invasion, tumor size, lymph node metastasis and stage were not correlated with COX-2 expression. Multivariate analysis for the factors associated with survival showed that serum CEA, size, depth and lymph node involvement correlated with survival, but COX-2 expression had no correlation. CONCLUSION: These data suggest that COX-2 expression in primary lesion of colorectal cancer may not be a useful marker for evaluating prognosis. However, further studies are necessary for identification of the roles in colorectal carcinogenesis.
Carcinogenesis ; Colorectal Neoplasms* ; Cyclooxygenase 2* ; Cytoplasm ; Epidemiologic Studies ; Humans ; Immunohistochemistry ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Prostaglandin-Endoperoxide Synthases*

PURPOSE: The aim of this study was to investigate the relationship of cyclooxygenase (COX)-2 expression and microvessel density (MVD), a reflection of angiogenesis, with prognosis in patients with transitional cell carcinoma of the upper urinary tract (TCC-UUT). MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissue sections of TCC-UUT from 91 patients, who had undergone radical nephroureterectomy, were examined immunohistochemically using antibodies against COX-2 and CD34. MVD was determined with CD34-stained slides. The expression patterns of COX-2 and MVD were compared with the clinicopathological variables. RESULTS: The COX-2 expression was significantly correlated with T stage (p=0.002), N stage (p=0.010), and grade (p=0.027). MVD was also significantly correlated with T stage (p<0.001), N stage (p=0.002), and grade (p=0.001). The COX-2 expression was significantly correlated with MVD (p=0.001). The survival rate of patients with COX-2 positive tumors or high MVD was significantly lower than that of patients with COX-2 negative tumors or low MVD, respectively (p=0.0013, p=0.0312). Univariate analyses identified T stage, N stage, grade, COX-2 expression, and MVD as significant prognostic factors for cancer-specific survival; multivariate analyses indicated that T stage was the only independent prognostic factor. CONCLUSIONS: The increased expression of COX-2 and MVD is associated with a worse prognosis in TCC-UUT. The COX-2 expression is correlated with MVD. These results suggest that COX-2 may play an important role in the progression of TCC-UUT and angiogenesis may be affected by COX-2 during the progression of TCC-UUT.
Antibodies ; Carcinoma, Transitional Cell* ; Cyclooxygenase 2* ; Humans ; Microvessels* ; Multivariate Analysis ; Prognosis* ; Prostaglandin-Endoperoxide Synthases ; Survival Rate ; Urinary Tract*

OBJECTIVE: The aim of this study was to identify the relation between HPV infection and cyclooxygenase 2 (COX-2) overexpression in cervical carcinoma in situ (CIS) and carcinoma. METHODS: Fourteen patients with CIS, 14 patients with invasive cervical carcinoma, and 14 patients with myoma as control were enrolled. Polymerase chain reaction was used to detect high risk types of HPV, and immunohistochemistry was used to detect COX-2 expression. RESULTS: The frequencies of high risk types of HPV infections in CIS or carcinoma were significantly higher than control [CIS: 11 (78.6%), carcinoma: 14 (100%), control: 1 (7.1%), P-value>0.001]. COX-2 expressions in CIS were higher than control (P=0.037), and those in carcinoma were higher than CIS (P=0.002). Three patients with CIS did not show HPV infection and showed lower COX-2 expression than the other patients with HPV infection in CIS group (P=0.013). There was strong correlation between COX-2 expression and HPV infection (P>0.001). However, in multivariate analysis, disease progression from normal to invasive carcinoma was the only independent factor to affect COX-2 overexpression. CONCLUSION: Disease progression from normal to invasive carcinoma might be more important factor to affect COX-2 overexpression than high risk types of HPV infection.
Carcinoma in Situ ; Cyclooxygenase 2 ; Disease Progression ; Humans ; Immunohistochemistry ; Multivariate Analysis ; Myoma ; Polymerase Chain Reaction ; Prostaglandin-Endoperoxide Synthases ; Uterine Cervical Neoplasms

OBJECTIVETo study the relation between cyclooxygenase-2 (COX-2) protein expression and biologic behavior of ovarian carcinoma.

METHODSThe level of COX-2 protein expression was detected by Western Blot assay in 54 biopsy specimens from ovarian serous tumor patients and 10 normal ovarian samples.

RESULTSThe level of COX-2 protein expression and relative quantity in ovarian serous carcinoma (81.8%, 20.08 +/- 3.53) were statistically higher than those in the benign ovarian serous tumor (0, 15.04 +/- 0.12) and in the normal ovary (0, 15.33 +/- 0.60) (P < 0.05). The level of COX-2 protein expression and relative quantity in borderline ovarian serous tumor (90.0%, 20.61 +/- 3.03) were statistically higher than those in benign ovarian serous tumor and the normal ovary (P < 0.05). The level of COX-2 protein expression and relative quantity were not significantly different from ovarian serous carcinoma and borderline ovarian serous tumor (P > 0.05); as they were between the benign ovarian serous tumor and the normal ovary (P > 0.05). The level of COX-2 protein expression and relative quantity were not significantly different among different clinical stages (I + II and III + IV), different histological grades, with or without ascites or lymphatic metastasis either.

CONCLUSIONCOX-2 overexpression may be significantly related to the oncogenesis and development of ovarian serous carcinoma, which may be an early diagnostic parameter and, hence, an attractive target for chemopreventive strategy in the treatment of ovarian serous carcinoma.

Adult ; Aged ; Blotting, Western ; Cyclooxygenase 2 ; analysis ; genetics ; physiology ; Female ; Humans ; Middle Aged ; Ovarian Neoplasms ; enzymology ; etiology

BACKGROUND: Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer (CRC). We performed a network meta-analysis to summarize such evidence and assess the efficacy and safety of these agents. METHODS: We searched PubMed, Embase, and the Cochrane Library for studies published in English until October 31, 2021 that fit our inclusion criteria. We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of candidate agents (low-dose aspirin [Asp], high-dose Asp, cyclooxygenase-2 inhibitors [coxibs], calcium, vitamin D, folic acid, ursodeoxycholic acid [UDCA], estrogen, and progesterone, alone or in combination) for preventing colorectal adenoma and CRC. Cochrane risk-of-bias assessment tool was employed to evaluate the quality of each included study. RESULTS: Thirty-two randomized controlled trials (278,694 participants) comparing 13 different interventions were included. Coxibs significantly reduced the risk of colorectal adenoma (risk ratio [RR]: 0.59, 95% confidence interval [CI]: 0.44-0.79, six trials involving 5486 participants), advanced adenoma (RR: 0.63, 95% CI: 0.43-0.92, four trials involving 4723 participants), and metachronous adenoma (RR: 0.58, 95% CI: 0.43-0.79, five trials involving 5258 participants) compared with placebo. Coxibs also significantly increased the risk of severe adverse events (RR: 1.29, 95% CI: 1.13-1.47, six trials involving 7109 participants). Other interventions, including Asp, folic acid, UDCA, vitamin D, and calcium, did not reduce the risk of colorectal adenoma in the general and high-risk populations compared with placebo. CONCLUSIONS: Considering the balance between benefits and harms, regular use of coxibs for prevention of colorectal adenoma was not supported by the current evidence. Benefit of low-dose Asp for chemoprevention of colorectal adenoma still requires further evidence. REGISTRATION PROSPERO, No. CRD42022296376.
Humans ; Cyclooxygenase 2 Inhibitors ; Calcium ; Network Meta-Analysis ; Vitamins ; Colorectal Neoplasms/drug therapy* ; Chemoprevention ; Aspirin ; Adenoma/prevention & control* ; Vitamin D

It has been reported that p53 mutation may contribute to upregulate cyclooxygenase (COX)-2 expression that is observed in malignant tissues. These molecules are involved in carcinogenesis by affecting tumor cell proliferation. The aim of this study was to examine the relationship between COX-2 or p53 expression and clinico-pathological characteristics including tumor cell proliferation in gastric cancer. COX-2 and p53 expressions were investigated with immunostaining, in tissue specimens obtained from 119 patients who underwent surgery for gastric cancer. The Ki-67 labeling index (LI) was counted by Ki-67 immunostaining. COX-2 and p53 expressions correlated significantly with depth of tumor invasion. However, there was no association between COX-2 or p53 expression and survival. p53 expression did not correlate with COX-2 expression. There was no significant difference in various clinicopathological variables between Ki-67 LI subgroups. The mean Ki-67 LI value of COX-2 positive tumors was significantly higher than that of negative tumors. The mean Ki-67 LI value of p53 positive tumors was not significantly higher than that of negative tumors. The mean Ki-67 LI value of both COX-2 and p53 positive tumors was significantly higher than that of both negative tumors. These results imply that COX-2 expression is associated with tumor cell proliferation of gastric cancer.
Tumor Suppressor Protein p53/*analysis ; Stomach Neoplasms/*chemistry/mortality/pathology ; Prognosis ; Middle Aged ; Male ; Ki-67 Antigen/*analysis ; Immunohistochemistry ; Humans ; Female ; Cyclooxygenase 2/*analysis ; Aged ; Adult

OBJECTIVETo evaluate the detection of fecal PPAR-delta and COX-2 mRNA in screening of colorectal cancer.

METHODSFifty-one patients with colorectal cancer and 21 healthy controls were included in this study. Total RNA was isolated from the fecal samples. Expression of PPAR-delta and COX-2 mRNA was determined by RT-PCR, and its value in screening of colorectal cancer was investigated.

RESULTSThe positive detection rate of fecal PPAR-delta and COX-2 mRNA in colorectal cancer patients was significantly higher than that in healthy controls. In 47 colorectal cancer patients and 19 healthy controls with positive fecal ACTB mRNA expression, the sensitivity of fecal PPAR-delta mRNA, COX-2 mRNA and PPAR-delta mRNA plus COX-2 mRNA detection in diagnosing colorectal cancer was 76.6%(36/47), 80.9%(38/47) and 91.5%(43/47) respectively; the specificity was 63.2%(12/19), 84.2%(16/19) and 89.5%(17/19) respectively.

CONCLUSIONThe combination detection of fecal PPAR-delta and COX-2 mRNA is effective in screening human colorectal cancer and is better than detection of single marker alone.

Aged ; Case-Control Studies ; Colorectal Neoplasms ; diagnosis ; Cyclooxygenase 2 ; analysis ; Early Detection of Cancer ; Feces ; chemistry ; Female ; Humans ; Male ; Middle Aged ; PPAR delta ; analysis ; RNA, Messenger ; analysis