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 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.
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.
Objective To investigate the effects of celecoxib-poly lactide-co-glycolide microparticles (CEL-PLGA-MS) on rat retina after intravitreal injection. Methods A total of 32 male Brown Norway rats were randomly divided into CEL-PLGA-MS group and celecoxib group, 16 rats in each group. The rats in CEL-PLGA-MS group were divided into four dosage group, four rats in each group, which received intravitreal injection of PLGA with celecoxib at the concentration of 40, 80, 160, 320 mu;mol/L, respectively. The rats in celecoxib group were divided into four dosage group, four rats in each group, which received intravitreal injection of celecoxib at the concentration of 40, 80, 160, 320 mu;mol/L, respectively. Phosphate buffer solution (PBS) was injected in two rats as PBS control group. Two rats as normal control group received no treatment. The difference of retinal thickness among groups was measured by optical coherence tomography (OCT). The morphological and histological change of retina was evaluated under light microscope and transmission electron microscope. Results There was no difference of retinal thickness between normal control group and PBS control group (F=0.12,P＞0.05). At the first week after injection, the retinal thickness of CEL-PLGA-MS group and celecoxib group were thicker than that in normal control group and PBS control group (F=9.62, 46.13;P＜0.01). The retinal thickness of celecoxib group was thicker than that in CEL-PLGA-MS group (F=165.15,P＜0.01). The retinal thickness was estimated equal among 40, 80, 320 mu;mol/L dosage groups in CEL-PLGA-MS group (F=4.79,P＜0.01). The retinal thickness of 160, 320 mu;mol/L dosage group were thicker than that in 40, 80 mu;mol/L dosage group in celecoxib group (F=28.10,P＜0.01). At the second week after injection, there was no difference of retinal thickness between CEL-PLGA-MS and celecoxib group (F=3.79,P＞0.05); the retinal thickness of CEL-PLGA-MS and celecoxib group became thinner gradually compare to the first week after injection (F=7.28, 103.99; P＜0.01). At the fourth week after injection, the retinal thickness of celecoxib group was thicker than that in CEL-PLGA-MS group (F=19.11,P＜0.01). The retinal thickness of CEL-PLGA-MS group was approximately the same to normal control group and PBS control group (F=2.02,P＞0.05). The retinal thickness of celecoxib group was thicker than that in normal control group and PBS control group. No considerable abnormality of the retina was seen by light microscope and the retinal thickness corresponded with the values measured by OCT at the first week after injection. The abnormal structures of the retina were seen in 160, 320 mu;mol/L dosage group of celecoxib group and inner changed evidently by the transmission electron microscope. Disordered arrangement of microfilaments, dilated microtubule and some mitochondria vacuolation were observed in 320mu;mol/L dosage group of celecoxib group. Others changed slightly. Conclusions CEL-PLGA-MS has less toxicity on the retina than free-celecoxib after intravitreal injection. The safety of intravitreal injection with CEL-PLGA-MS is better than celecoxib.
【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.
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.
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 observe the effect of panretinal photocoagulation (PRP) on the expression of cyclooxygenase-2 (COX-2), vascular endothelial cell growth factor (VEGF) in epiretinal membrane of proliferative diabetic retinopathy (PDR). Methods Atotal of 35 patients (35 eyes) with PDR and underwent plana vitrectomy were enrolled in this study. The patients were divided into non-PRP group (19 patients, 19 eyes) and PRP group (16 patients, 16 eyes) depends on if they had received PRP before surgery. The epiretinal membranes stripped during operation were collected for pathological examination. The histopathological features was observed by haematoxylin and eosin stain. The expression of CD34, COX-2 and VEGF, and microvessel density (MVD) were measured by immunohistochemistry method. Results Many new dispersed capillary blood vessels were found in the thick epiretinal membranes of non-PRP group, while scattered small blood vessels were found in the relatively thin epiretinal membranes of PRP group. MVD value was (7.42±1.39) in the non-PRP group and (4.56±1.22) in the PRP group, which was lower than the non-PRP group (t=6.41, P<0.01). The expression of CD34, COX-2 and VEGF in the tissues of epiretinal membrane in PRP group were obviously lower than the non-PRP group (t=6.147, 5.944, 7.445; P<0.01). Conclusion PRP can effectively inhibit the expression of COX-2 and VEGF in epiretinal membrane of PRP patients.
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.