【Abstract】Objective To study the expression of cyclooxygenase-2 (COX-2) in hepatic inflammatory reaction of rats with sepsis, and to explore a new way of protecting hepatic cell. Methods Fifty-four Wistar rats were randomly divided into 3 groups: sham operation group, sepsis group and NS398 group. All rats were subjected to cecal ligation and puncture (CLP) or sham operation. RT-PCR was used to determine COX-2 mRNA expression, serum IL-6, TNF-α and IL-10 were determined by ELISA; and ALT and AST and liver pathological changes were determined in 3 groups and at different times (3, 6, 12 and 24 h) respectively. Results ①The expression of COX-2 mRNA of hepatic tissue was low in sham operation group. It obviously enhanced after CLP at 3 h and peaked at 6 h. High expressions were showed at 12 and 24 h. In NS398 group, it was lower than that of sepsis group at the same time, but higher than that of sham operation group. ②Serum ALT, AST and IL-6, TNF-α were increased in sepsis group than those of sham operation and NS398 group (P＜0.05)； Serum IL-10 was higher in NS398 group than that of sham operation and sepsis group (P＜0.05). ③Hepatic pathological injury extenuate after injected with NS398. Conclusion COX-2 may play an important role in hepatic injury with sepsis.
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.
Objective To investigate the expression and clinical significance of cyclooxygenase-2 (COX-2) in human breast cancer with meta-analyses. Methods The published studies were searched in the CBM, CNKI, VIP and WanFang databases, and other relevant journals were also handsearched 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 8 studies were recruited. As for the positive rate of COX-2 expression, significant differences were tested between breast cancer vs. normal breast tissues, cell differentiation G1 vs. cell differentiation G2-G3 with OR (95%CI) at 16.36 (9.18, 29.15) and 0.34 (0.18, 0.63), respectively. No significant difference was tested between lymph node metastasi vs. non-lymph node metastasi, clinical stages I-II vs. clinical stages III-IV with OR (95%CI) at 1.36 (0.61, 3.03) and 0.61 (0.34, 1.10), respectively. Conclusion According to the domestic evidence, COX-2 may be participated the whole course of carcinogenesis of breast cancer, but is not the absolute factor for estimating the survival rate of the patients with breast cancer, and more high-quality studies are expected for further study.
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.
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.
ObjectiveTo systematically review the association between -765 G > C (rs20417) polymorphism of cyclooxygenase-2 (COX-2) gene and the risk of gastric cancer (GC).
MethodsSuch databases as PubMed, EMbase, The Cochrane Library (Issue 10, 2015), CBM, CNKI, VIP and WanFang Data were searched from inception to October 2015 to collect case-control studies about the correlation between -765 G > C (rs20417) polymorphism of COX-2 gene and GC. Two reviewers independently screened literature, extracted data and evaluated the quality of included studies. Meta-analysis was performed using Stata 12.0 software.
ResultsA total of 15 case-control studies were included in this meta-analysis, including 2 891 cases and 4 967 controls. Meta-analysis showed that the -765 G > C (rs20417) polymorphism was significantly associated with the risk of GC (OR=1.70, 95%CI 1.21 to 2.38, P=0.002). Subgroup analysis showed there was a significant association between the -765 G > C (rs20417) polymorphism and GC in Asians (OR=2.24, 95%CI 1.70 to 2.96, P=0.000); However, no association was found in the Caucasians and Americans. In the subgroup analysis by Helicobacter pylori (H. pylori) status, there were statistical significances between helicobacter pylori (+) and helicobacter pylori (-) with the risk of GC in COX-2 polymorphism of CC/CG vs. GG (OR=2.11, 95%CI 1.41 to 3.14, P < 0.001).
ConclusionThe COX-2-765 G > C (rs20417) polymorphism may be significantly associated with an increased risk of GC, especially among Asians.
【Abstract】Objective To investigate the relationship of expressions of cylooxygenase-2 (COX-2) and hypoxia-inducible factor-1α (HIF-1α) in hepatocelluar carcinoma (HCC) and the possible antineoplastic mechanism of selective COX-2 inhibitor. Methods The expressions of COX-2 and HIF-1α in 53 cases of HCC tissues were detected immunohistochemically. Western blot was employed to evaluate the effects of variant concentration of COX-2 inhibitor meloxicam on expression of HIF-1α in Cobaltchloridestimulated SMMC-7721 cell. ResultsOf 53 tumor tissues, the expression of COX-2 was 22/53 (41.5%) bly positive stained, 11/53 (20.8%) positive stained, and 20/53 (37.7%) negative stained. Meanwhile the expression of HIF-1α was 18/53 （34.0%） bly positive stained, 18/53 （34.0%）positive stained, 17/53（32.1%） negative stained. The expression of COX-2 was correlated positively with HIF-1α in HCC （r=0.440, P＜0.01）. The expression of HIF-1α increased sharply from 0.185±0.057 (no Cobaltchloride-stimulated) to 1.011±0.131 (Cobaltchloride-stimulated), and meloxicam could inhibit the expression of HIF-1α at either condition (P＜0.05). ConclusionMeloxicam could inhibit the expression of HIF-1α in a concentration-dependent manner in the Cobaltchloridestimulated SMMC-7721 cell. The antineoplastic activity of selective COX-2 inhibitor was possibly, at least in part, mediated by HIF-1α.
ObjectiveTo explore the correlation between -765G/C polymorphism of cyclooxygenase-2 (COX-2) gene and the risk of ischemic stroke (IS).
MethodsPubMed, CBM, The Cochrane Library (Issue 3, 2015), CNKI, CBM, VIP and WanFang Data were searched from inception to March 2015 to collect case-control or nested case-control studies about -765G/C polymorphism of COX-2 gene and the risk of IS. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.1 software and Stata 12.0 software.
ResultsA total of 10 studies involving 2611 cases and 18589 controls were included. The results of meta-analysis showed that, there was no correlation between -765G/C polymorphism and the risk of IS (GC+CC vs. GG: OR=1.05, 95%CI 0.88 to 1.25, P=0.620; CC vs. GG+GC: OR=1.04, 95%CI 0.83 to 1.30, P=0.730; GC vs. GG: OR=1.04, 95%CI 0.87 to 1.25, P=0.630; CC vs. GG: OR=1.09, 95%CI 0.86 to 1.36, P=0.480; C vs. G: OR=1.03, 95%CI 0.89 to 1.20, P=0.700). Subgroup analysis results showed that, the COX-2 gene -765G/C polymorphism was a risk factor for IS in African-Americans (GC+CC vs. GG: OR=1.42, 95%CI 1.12 to 1.78, P=0.003; GC vs. GG: OR=1.39, 95%CI 1.09 to 1.78, P=0.008; CC vs. GG: OR=1.51, 95%CI 1.04 to 2.18, P=0.030; C vs. G: OR=1.27, 95%CI 1.08 to 1.51, P=0.004), but not in Asians and Caucasians.
ConclusionCurrent evidence shows that -765G/C polymorphism of COX-2 gene may be a genetic risk factor for IS in African-Americans, but not in Asians and Caucasians. Due to the limited quantity and quality of the included studies, more high quality studies are needed to verify the above conclusion.
【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.
ObjectiveTo investigate the expression of keratinocyte growth factor (KGF) and cyclooxygen-ase-2 (COX-2) protein and microvessel density (MVD), and to explore their function and mechanism in the multistep process of gastric cancer. MethodsThe expressions of KGF and COX-2 protein in 64 samples of gastric cancer and 30 cases of normal gastric mucosa tissues were detected by immunohistochemistry. The MVD was detected by staining the endothelial cells in microvessles using anti-CD34 antibody. ResultsThe positive rate of KGF and COX-2 protein expression in gastric cancer were 65.6% (42/64) and 79.7% (51/64), respectively, which was significantly higher than that in normal gastric mucosa tissues 〔(23.3%, 7/30), P=0.046; (13.3%, 4/30), P=0.008〕. The MVD of gastric cancer was 31.8±8.0, which was significantly higher than that of normal gastric mucosa tissues (14.3±6.1), P=0.000. The MVD in gastric cancer with coexpressive KGF and COX-2 protein was 35.9±5.7, which was significant higher than that with non-coexpressive KGF and COX-2 protein (25.7±7.0), P=0.000. Both the expression of KGF and COX-2 protein were related to the invasion of serosa, lymph node metastasis and TNM staging (Plt;0.05, Plt;0.01). The MVD of gastric cancer tissues was related to lymph node metastasis and TNM staging (Plt;0.05), but unrelated to patient’s age, gender, and differentiation of tumor (Pgt;0.05). The co-expression of KGF and COX-2 protein was frequently found in patients with deeper invasion of serosa, lymph node metastasis, and higher TNM staging (Plt;0.05), but which was not associated withpatient’sage, gender, and differentiation of tumor (Pgt;0.05). The expression of KGF protein was positively correlated to the expression of COX-2 protein (r=0.610, P=0.000). There was positive correlation between MVD and the expression of KGF (r=0.675, P=0.000) and COX-2 protein (r=0.657, P=0.000) in gastric cancer, respectively. ConclusionKGF and COX-2 highly expressed by gastric cancer, which may be involved in the invasion and metastasis of gastric cancer by synergisticly promoting the angiogenesis.
