【Abstract】 Objective To study the expressions of cyclooxygenase-2 (Cox-2) and angiopoietin-2 (Ang-2) in colorectal cancer tissues, cancer adjacent tissues and normal colorectal tissues, and the relationship between these expressions and the clinicopathologic features of colorectal cancer. Methods Forty-five excised samples of colorectal adenocarcinoma were confirmed pathologically and 39 of them were of well or moderately differentiated and 6 of poorly differentiated. Lymph nodes metastasis developed in 30 patients. And 15 cases were in stage of A or B and the rest were in the stage of C or D according to the Dukes stage. Taken PBS as the negative control and the verified Cox-2 or Ang-2 positive sections as positive controls, this study detected the expressions of Cox-2 and Ang-2 protein in 45 colorectal cancer tissues, 45 cancer adjacent tissues and 15 normal colorectal tissues by using immunohistochemical SP technique method. Results Cox-2 and Ang-2 were expressed in colorectal cancer tissues and cancer adjacent tissues, but were not expressed in normal colorectal tissues. In 45 colorectal cancer tissues, the positive expression rates of Cox-2 and Ang-2 were 80.0% and 66.7%; in 45 cancer adjacent tissues, the positive expression rates of Cox-2 and Ang-2 were 35.6% and 11.1%, respectively. The positive expression rates of both Cox-2 and Ang-2 in colorectal cancer tissues were significantly higher than those in cancer adjacent and normal colorectal tissues. There were close correlations between the expressions of Cox-2 and Ang-2 and some pathologic features, such as lymph node metastasis and Dukes stage; whereas there were no significant association between the expressions and gender, histological type and position of tumor. There was also a close correlation between the expressions of Cox-2 and Ang-2 themselves. Conclusion Cox-2 and Ang-2 play an important role in the occurrence and development of colorectal cancer. The use of specific inhibitor of Cox-2 as a treatment for colorectal cancer may become feasible and necessary.
ObjectiveTo investigate the expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in human pancreatic adenocarcinoma and their correlation with clinicobiological behavior.MethodsThe expression of COX-2 and VEGF in 51 cases of human pancreatic ductal adenocarcinoma were detected with immunohistochemistry of Envision.ResultsExpression of COX-2 and VEGF in pancreatic ductal adenocarcinoma were 74.5% and 68.6%, respectively; no expression of COX-2 and VEGF in adjacent normal tissue was detected. Both COX-2 and VEGF expression in clinical stage Ⅲ-Ⅳ were much higher than those in clinical stage Ⅰ-Ⅱ, and also higher in positive group of lymph node metastasis than in negative group as well (Plt;0.05). None of them had relation with histological grades, age, sex, tumor size and location. The expression of COX-2 was closely correlated with VEGF (r=0.411, Plt;0.01).ConclusionCOX-2 and VEGF may play a pivotal role in tumorigenesis and tumor progression in pancreatic cancer, they may provide new targets for therapy of pancreatic cancer.
Objective To study the interaction and mechanism of prostaglandin I2 (PGI2) receptor/thromboxane A2 (TxA2) receptor (IP/TP) and cyclooxygenase-2 (COX-2) in ischemia reperfusion injury after liver transplantation of rat. Methods Rats were randomly divided into three groups: control group （n=16), orthotropic liver transplantation group （n=32) and nimesulide intervention group （n=32). The samples were obtained at 3 h, 6 h, 12 h and 24 h after operation. The expressions of COX-2, IP and TP mRNA were detected by RT-PCR. Immunohistochemistry was used to detect the localization and expression of COX-2. Hematoxylin Eosin staining was used to classify the injury extent of liver. Serum ALT and AST levels were detected to evaluate the changes of liver enzyme. Results COX-2 protein expression detected by immunohistochemistry in orthotropic liver transplantation group mainly distributed in the district of liver sinusoidal endothelial cells, liver cells and macrophage cells, which was significantly higher than control group and nimesulide intervention group. Expressions of IP mRNA, TP mRNA and COX-2 mRNA in the orthotropic liver transplantation group were significantly increased than those in control group (P＜0.05), and the ratio of IP/TP increased (P＜0.05). Expressions of IP mRNA and TP mRNA in nimesulide intervention group were significantly lower than that in the orthotropic liver transplantation group at 6 h and 12 h after operation (P＜0.05), and the ratio of IP/TP decreased at 3 h, 6 h and 24 h after operation (P＜0.05). The expression of COX-2 mRNA in nimesulide intervention group was significantly lower than that in the orthotropic liver transplantation group at 6 h, 12 h and 24 h after operation. In orthotropic liver transplantation group liver injury was obvious by HE staining, and more severve than that in nimesulide intervention group. Serum AST (each time) and ALT (3 h, 6 h and 12 h) levels in the orthotropic liver transplantation group were significantly higher than that in control group and nimesulide intervention group (P＜0.05) and peaked at 6 h after operation. Conclusion The balance of IP/TP takes part in and plays an important role in the ischemia reperfusion injury of liver transplantation. Changing imbalance of IP/TP may reduce liver transplantation ischemia reperfusion injury by inhibiting COX-2 expression.
Objective To investigate the expression of COX-2 in human cervical cancer and explore their relationship between the COX-2 expression and the clinicopathologic characteristic of cervical cancer. Methods The published studies were searched in the CBMdisc (1979 to 2009), CNKI (1979 to 2009), VIP (1989 to 2009) and WANFANG Database (1982 to 2009), and other relevant journals were also hand searched, to identify all the relevant case-control trials. The quality of the included studies was assessed. The Cochrane Collaboration’s software RevMan 4.2.10 was used to test the heterogeneity, overall effect and publication bias of the combined studies. Results A total of 9 studies were recruited. As for the positive rate of COX-2 expression, significant differences was tested between cervical cancer vs. normal cervical tissues, lymph node metastasi vs. non-lymph node metastasi, clinical stages I-II vs. clinical stages III-IV, cell differentiation G1 vs. cell differentiation G2-G3 and cervical squamous cell carcinoma vs. adenocarcinoma with OR (95%CI) at 28.03 (9.53 to 82.50), 5.16 (3.36 to 7.93), 0.53 (0.33 to 0.84), 3.11 (1.86 to 5.22) and 5.00 (2.68 to 9.35) respectively. Conclusions According to the domestic evidence, higher COX-2 expression might be associated with cervical cancer. However, more high quality case-control studies are expected for further study.
Objective To summarize the research progress in antitumor mechanism of non-steroidal anti-inflam-matory drugs. Methods The domestic and international published literatures about antitumor mechanism of non-steroidal anti-inflammatory drugs in recent years were reviewed. Results The antitumor mechanism of non-steroidal anti-inflam-matory drugs was multistrata and multidigit. Conclusion Non-steroidal anti-inflammatory drugs can be used to prevent the development of colorectal cancer and also be a adjuvant therapy after radical operation for colorectal cancer.
Objective To investigate the expression of cyclooxygenase-2 (COX-2) in liver tissue of severe acute pancreatitis (SAP) rats. Methods A rat model of SAP was induced by retrograde infusion of 3.5% sodium taurocholate into the biliary-pancreatic duct. Eighty rats were randomly divided into SAP group and control group. The levels of serum amylase (AMY), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor (TNF) -α and ascites AMY were detected dynamically at 4 h, 8 h, 16 h and 24 h after operation. The pancreatic and liver injuries were observed by light microscope. The expression of COX-2 in liver tissue was measured by immunohistochemistry. Results Compared with the control group, the levels of serum AMY, ALT, AST, TNF-α and ascites AMY increased significantly at the time point of 4 h, 8 h, 16 h and 24 h (Plt;0.05). These changes were paralleled with the histopathological changes of pancreatic and liver tissue. The expression positive rates of COX-2 at the different time in the SAP group were higer than those of the control group (Plt;0.05). There was a significantly positive correlation between the expression of COX-2 and ALT (rs=0.949, P=0.039), AST (rs=0.972, P=0.016) and serum AMY (rs=0.944, P=0.041), respectively. Conclusion Overexpression of COX-2 may play an important role in liver injury during SAP.
Objective To systematically evaluate the efficacy and safety of injected cyclooxygenase-2 inhibitor for acute postoperative pain. Methods We electronically searched PubMed, EBSCO, Springer, Ovid and CNKI databases from 1999 through Jan. 2009 to identify randomized controlled trials (RCTs) about cyclooxygenase-2 inhibitor or parecoxib sodium for acute postoperative pain. The methodological quality of included RCTs were assessed, and the data was extracted by two reviewers independently according to the Cochrane Handbook. The homogeneous RCTs were pooled using RevMan software, and the non-homogeneous studies evaluted using descriptive qualitative analysis. Results Seven RCTs involving 1939 patients met the inclusion criteria. The results of meta-analyses showed that: ① Efficacy: The comparison of PCA combined parecoxib sodium (successively injected less than 3 days) i.v. with PCA alone: after 24, 48, and 72 hours of the initial dose of parecoxib 40 mg i.v., the percentage of the patients’ global evaluation of study medication (PGESM) described effective (excellent and good) was higher than that of the control group [RR (95%CI) were 1.41 (1.13, 1.75), 1.25 (1.15, 1.35), and 1.30 (1.21, 1.40) respectively]; the percentage of the PGESM described ineffective (fair and poor) was lower than that of the control group [RR (95%CI) were 0.43 (0.26, 0.72), 0.44 (0.34, 0.57), and 0.33 (0.23, 0.48) respectively]. ② Safety: Combination of PCA with parecoxib sodium could lessen the incidence of postoperative fever (RR=0.34, 95%CI 0.22 to 0.53) and nausea and vomiting (RR=0.69, 95%CI 0.57 to 0.83), but not statistically decrease of respiratory depression (RR=0.84, 95%CI 0.38 to 1.83), pruritus (RR=0.91, 95%CI 0.54 to 1.52), and headache (RR=0.77, 95%CI 0.47 to 1.28). Conclusion The combination of PCA with parecoxib sodium successively injected less than 3 days can significantly increase the scores of PGESM, and does not increase the incidence of adverse effects or postoperative complications, and also has the advantage of decreasing postoperative fever, nausea and vomiting.
【Abstract】ObjectiveTo investigate the effects of nimesulide, a selective cyclooxygenase-2 (COX-2) inhibitor, on human cholangiocarcinoma QBC939 cell line in vitro. MethodsThe effects of nimesulide on QBC939 cells were observed with the following techniques: the influence of nimesulide on the proliferation of QBC939 cells was determined by MTT assay; the apoptosis of QBC939 cells was viewed and measured by transmission electron microscopy and flow cytometry, respectively; the expressions of proliferation cell nuclear antigen (PCNA) and COX-2 of cholangiocarcinoma cells were detected by immunocytochemistry. ResultsNimesulide inhibited the expressions of PCNA and COX-2 and the proliferation of cholangiocarcinoma QBC939 cells, whose effects intensified as the dose increased and time elongated. Flow cytometry showed that the apoptotic rates of QBC939 cells increased significantly as the dose of nimesulide increased. The typical morphologic features of apoptosis were also observed by transmission electron microscopy. ConclusionNimesulide significantly inhibits the proliferation of QBC939 cells in vitro by inducting cell apoptosis, which may be associated with the downregulation of COX-2 expression, and it also presents the features of dose and time dependents.
Objective To detect the expressions of epidermal growth factor receptor (EGFR), epidermal growth factor receptor-2 (C-erbB-2), vascular endothelial growth factor (VEGF) and cyclooxgenase-2 (COX-2) in gastric cancer tissues, and to analyze the relationship among them and the clinicopathologic factors of gastric cancer. Methods The SP immunohistochemical stain was used to detect EGFR, C-erbB-2, VEGF and COX-2 protein expressions in sample of 68 gastric cancer tissues. And their corresponding clinical data were analyzed retrospectively. Results The expression rates of EGFR, C-erbB-2, VEGF and COX-2 protein in gastric cancer tissue were 38.2% (26/68), 42.6% (29/68), 52.9% (36/68) and 60.3% (41/68) corresponding. An obvious increasing tendency as the differentiation of the cancer degraded, invasion depth deepened, lymphatic metastasis occurred and TNM stage upgraded was showed by the positive expression rates of them （P＜0.05，P＜0.01）; but there was no correlation with the patient’s sex, age, tumour site and size （Pgt;0.05）. There was a stable positive correlation among EGFR, C-erbB-2, VEGF and COX-2 expressions in gastric cancer tissue, respectively （P＜0.05）. Conclusion EGFR, C-erbB-2, VEGF and COX-2 expressions participate in the development, invasion and metastasis process of gastric cancer. Joint detection of them can be looked as an important symbol for judging the prognosis of gastric cancer and screening the high-risk metastasis patients, and guiding the molecular targeting therapy of gastric cancer.
ObjectiveTo study the expressions of cyclooxygenase-2(COX-2) and Ki-67 in the invasive ductal carcinoma (IDC) of breast and to analyze its clinical significance. MethodsImmunohistochemical SP method was performed to detect the expressions of COX-2 and Ki-67 in 82 cases of IDC of breast and corresponding tumor-adjacent normal breast tissues, and the relationship of these expressions to clinicopathologic characteristics was analyzed. Results①The positive rates of COX-2 and Ki-67 protein expressions in the IDC of breast tissues were significantly higher than those in the corresponding tumor-adjacent normal breast tissue [COX-2:71.95%(59/82) versus 8.54%(7/82), χ2=68.56, P < 0.001;Ki-67:64.63%(53/82) versus 13.42%(11/82), χ2=45.20, P < 0.001].②The positive rates of COX-2 and Ki-67 protein expressions were positively correlated with TNM staging (COX-2:rs=0.349, P < 0.05;Ki-67:rs=0.305, P < 0.05), lymph node metastasis (COX-2:rs=0.336, P < 0.05;Ki-67:rs=0.419, P < 0.01), vascular invasion (COX-2:rs=0.235, P < 0.05;Ki-67:rs=0.461, P < 0.01), and histological grade (COX-2:rs=0.434, P < 0.01;Ki-67:rs=0.378, P < 0.05).The positive rate of Ki-67 protein expression was positively correlated with tumor diameter (rs=0.365, P < 0.01), but the positive rate of COX-2 protein expression wasn't correlated with it (rs=0.135, P > 0.05).The positive rates of COX-2 and Ki-67 protein expressions weren't correlated with menstrual status (COX-2:rs=0.172, P > 0.05;Ki-67:rs=0.163, P > 0.05).③The positive rate of COX expression was positively correlated with the positive rate of ki-67 expression (rs=0.475, P < 0.01). ConclusionsThere are high-expressions of COX-2 and Ki-67 in IDC of breast.COX-2 and Ki-67 are significantly correlated with the clinicopathologic characteristics in IDC of breast.Combined detection of COX-2 and Ki-67 might calculate the biological behaviors of IDC of breast.COX-2 might be a target of molecular targeted therapy to breast cancer.