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.
ObjectiveTo observe the effect of lentivirus-mediated cyclooxygenase 2 (COX-2) and Aggrecanase-1 silencing and insulin-like growth factor 1 (IGF-1) in BMSCs after injecting into the knee joint cavity in cynomolgus monkeys with knee osteoarthritis (OA). MethodsBMSCs were isolated from the bone marrow of 10 donors. The lentivirus vector expressing genes of COX-2, Aggrecanase-1, and IGF-1 were constructed, and transfected into the third generation human BMSCs at 40 multiplicity of infection (virus group); BMSCs transfected with lentivirus-empty vector served as blank-virus group. The growth status and number of BMSCs were observed under inverted phase contrast microscope, and normal BMSCs were used as normal control group. At 1 week after transfected, the mRNA expressions of COX-2, Aggrecanase-1, and IGF-1 were detected with RT-PCR. Nine 3-year-old cynomolgus monkeys were selected to establish the OA model according to Hulth modeling method, and were randomly divided into 3 groups (n=3). At 6 weeks after remodeling, the right knee joint cavity was injected accordingly with 1 mL BMSCs (about 1×107 cells) in virus group and blank-virus group, with 1 mL of normal saline in the blank control group; the left knee served as normal controls. The general condition was observed after injection; at 1, 4, and 6 weeks, the concentrations of prostaglandin E2 (PGE2), IL-1, Aggrecanase-1, and IGF-1 of double knee liquid were detected with ELISA; at 6 weeks, MRI, general observation, histology method, and immunohistochemistry method were used to detect the knee cartilage changes and the expressions of COX-2, Aggrecanase-1, and IGF-1 were measured with RT-PCR. ResultsNo significant difference was found in cell morphology and growth curve between 2 groups after transfection. By RT-PCR, COX-2, and Aggrecanase-1 expressions were significantly reduced, IGF-1 expression was significantly increased in virus group when compared with normal control group and the blank-virus group (P < 0.05). All monkeys survived to the end of the experiment after injection. When compared with blank-virus group and blank control group, the concentrations of PGE2, Aggrecanase-1, and IL-1 significantly decreased and the concentration of IGF-1 significantly increased in the virus group (P < 0.05), but the indicators in 3 groups were significantly higher than those in the normal control group (P < 0.05). MRI showed that abnormal articular surface with high density could be found in virus group, blank-virus group, and blank control group, while the virus group had the minimum area. Gross observation and histological observation showed that the cartilage morphology of virus group, blank-virus group, and blank control group was accordance with early OA articular cartilage changes, but virus group was better than blank-virus group and blank control group in repair degree, whose improved Pineda score was significantly lower (P < 0.05). Immunohistochemical staining showed that the virus group had deeper dyeing with occasional brown particles and more chondrocytes than blank-virus group and blank control group. By RT-PCR, COX-2 and Aggrecanase-1 mRNA expressions of cartilage in virus group were significantly decreased, and IGF-1 expression was significantly increased when compared with blank control group and the blank-virus group (P < 0.05). ConclusionLentivirus-mediated multi-genes co-transfection in BMSCs can inhibit the expressions of COX-2 mRNA and Aggrecanase-1 mRNA, and enhance the IGF-1 mRNA expression, which decreases the concentration of inflammatory factors, and protects the joint cartilage effectively.
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.
ObjectiveTo explore the expressions of prostaglandin F2α receptor (PTGFR) and cyclooxygenase-2 (COX-2) in tissues of benign bile duct scar and their significances, and investigate the regulating effect of transforming growth factor-β1 (TGF-β1) on the expression of PTGFR in human bile duct fibroblasts cultured in vitro. MethodsThe samples of common bile duct (CBD) scars were collected from 18 patients with benign bile duct scar stricture and 6 cases of normal CBD tissues from liver transplantation donor were collected as control. The expressions of PTGFR and COX-2 were detected by immunohistochemical strept-avidin-biotin complex (SABC) method. Semiquantitative RT-PCR and ELISA methods were used to detect the mRNA and protein levels of PTGFR in bile duct fibroblasts which were effected by TGF-β1 with different concentrations (0, 10, 20, and 30 ng/ml) for 24 h. ResultsThe positive rates of PTGFR and COX-2 were 88.9% (16/18) and 83.3% (15/18) in tissues of benigh CBD scar and 33.3% (2/6) and 0 (0/6) in normal CBD tissues (Plt;0.05). The expressions of the PTGFR mRNA and protein levels became upregulated when the concentrations of the TGF-β1 became higher in human bile duct fibroblasts (Plt;0.05). And the effect was concentration dependant to some extent. ConclusionsThe high expressions of PTGFR and COX-2 play important roles in the process of benign bile duct stricture formation. TGF-β1 is able to induce higher expressions of PTGFR mRNA level and the PTGFR protein level in a concentration dependent manner, and regulate the formation of benign bile duct stricture.
Objective To investigate the effect of inducible nitric oxide synth ase (iNOS) or cyclooxygenase－2 (COX－2) on retinal neovascularization and its possible mechanism in oxygen－induced retinopathy （OIR） mouse model. Methods Retinal neovascularization was induced by oxygen with different concentration. The expression of iNOS, COX－2, matrix metalloproteinases 2 (MMP－2) and vascular end othelial growth factor (VEGF) in the retinae of experimental animals were analyzed by immunohistochemistry, realtime polymerase chain reaction and western blotting technologies. Results The inhibition of COX－2 or iNOS obviously attenuated retinal neovascularization and decreased the expression of VEGF and MMP－2. The iNOS inhibition decreased COX－2 expression, and vice versa. Conclusions COX－2 and iNOS may play a role in retinal neovascularization in OIR mouse model, which may act by regulating the expression of VEGF and MMP－2.
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 effects of selective cyclooxygenase-2 (COX-2) inhibitor nimesulide on the proliferation of colon adenocarcinoma cells in vitro and the expression of matrix metalloproteinase-2 (MMP-2). Methods The human colon cancer cell lines HT-29 and HCT-116 were employed in the study, grouped as nimesulide group, DMSO control group and blank control group. After treatment with nimesulide, the inhibitory effect of nimesulide on the proliferation of cancer cells was quantified by MTT assay, and the expression of MMP-2 in the cells was detected by quantitative zymography. Results Nimesulide inhibited the proliferation of HT-29 and HCT-116 cells in time and dosedependent manners. The inhibitory effect on HT-29 cells was ber than that on HCT-116 cells. Nimesulide downregulated the MMP-2 expression in HT-29 cells, whereas the expression in HCT-116 cells remained unchanged. Conclusion Nimesulide can obviously inhibit the growth of colon cancer HT-29 cells with positive COX-2 protein, suggesting that nimesulide may downregulate the expression of MMP-2 by inhibiting the activity of COX-2.
【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 observe the inhibition effect of selective cyclooxygenase2 inhibitor（celecoxib）on the experimental choroidal neovascularization（CNV）. Methods Thirty 8-10 weeks old healthy male Brown-Norway（BN）rats were randomly divided into the control, laser and celecoxib group,with 10 rats in each group. At the dosage of 50 mg/kg, celecoxib was gavaged twice per day. After 7 days, experimental CNV was induced by Krypon laser on laser group and celecoxib group. Fundus fluorescein angiography (FFA) was performed on days 3, 7,14,21,30 after laser photocoagulation.On days 21 after photocoagulation, 5 rats in each group were sacrificed and the relative thickness of CNV membranes, the expression of COX-2, vascular endothelial growth factor(VEGF) and matrix metalloproteinase-2(MMP-2) were studied by histopathologic or immunohistochemistry examination.Results On days 21 after photocoagulation, the incidence of CNV in the celecoxib group is significantly lower than that in the laser group (chi;2=7.1068,P=0.0077); the relative thickness of the CNV membranes in the celecoxib group is reduced 41.38% compared to the laser group, the difference is statistically significant (t=16.760 0，P=0.0000).COX-2,VEGF and MMP-2 expression in the CNV membrane of celecoxib group were significantly lower than in control group (t=5.710 0,5.840 0, 8.020 0; P=0.000 0); the COX-2, VEGF and MMP-2 expressions in choroid and retina of control group were weak. Conclusion Prophylactic celecoxib can reduce the expression of VEGF and MMP-2 by inhibiting COX-2, and prevent the CNV induced by laser photocoagulation.
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.