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 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.
The resistance of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been brought into focus. COX-2 signal pathway was found to be closely related to EGFR signal pathway by recent researches, and there has been a growing interest to focus the researches on whether COX-2 pathway inhibition improves the efficacy of EGFR-TKIs in treating advanced NSCLC. In this review, we will illustrate recent advances of combined inhibition of EGFR and COX-2 signal pathways in NSCLC therapy.
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.
目的 探讨环氧化酶-2（COX-2）在幽门螺杆菌（Hp）感染与非感染性胃溃疡及胃癌的表达。 方法 选择绵阳市404医院消化内科2011年2月－2012年2月的门诊及住院患者，用免疫组织化学方法检测196例经胃镜和组织病理学检查明确为胃溃疡（病理分型：肠上皮化生、异型增生）、胃癌及正常胃黏膜者的胃黏膜COX-2蛋白的表达，比较各病理分类之间及Hp感染与非感染之间COX-2蛋白表达的差异。 结果 胃溃疡（肠上皮化生、异型增生）、胃癌组的炎症细胞、腺上皮细胞、癌细胞及极少量正常黏膜上皮细胞中有COX-2表达。从正常胃黏膜-胃溃疡（肠上皮化生、异型增生）-胃癌COX-2的阳性表达有逐渐增强的趋势（P＜0.05）。Hp阳性组COX-2的阳性表达高于Hp阴性组（P＜0.05），胃癌组COX-2的阳性表达高于胃溃疡组（P＜0．05）。 结论 COX-2在胃癌的表达高于胃溃疡。Hp感染可诱导COX-2过度表达。
ObjectiveTo systemically evaluate the efficacy and safety of cyclooxygenase-2 (COX-2) signal pathway inhibition in treating advanced non-small cell lung cancer (NSCLC). MethodsA systematic literature search in PubMed, EMbase, Cochrane Library, ASCO databases, CNKI and Wanfang database was conducted to identify relevant randomized controlled trials (RCTs) from the time of database establishment to June 2015. RCTs of COX-2 inhibitors treating advanced NSCLC were included. We assessed the methodology quality of the included studies by using Jadad's scale, and performed this meta-analysis by using stata12.0 software. ResultsTwelve RCTs involving three different COX-2 inhibitors with a total of 1 828 patients were identified including 8 studies of high quality and 4 studies of low quality. We found that COX-2 signal pathway inhibition could significantly increase overall response rate at RR=1.27 with 95%CI1.10 to 1.46 (P=0.001). While our present data could not confirm the efficacy of COX-2 inhibitors in improving progression-free survival (PFS) at HR=0.93 with 95%CI0.81 to 1.08 (P=0.334), overall survival (OS) at HR=0.95 with 95%CI0.84 to 1.08 (P=0.461), or one-year survival rate at RR=1.08 with 95%CI0.90 to 1.24 (P=0.29). As for toxicities, only increased risk of thrombocytopenia at RR=1.28 with 95%CI 1.03 to 1.85 (P=0.03) was observed in the patients treated with COX-2 inhibitors. ConclusionCOX-2 signal pathway inhibition is effective in improving the overall response rate of the patients with advanced NSCLC, and is well tolerated. Whether COX-2 signal pathway inhibition is effective in improving long-term survival of the patients with advanced NSCLC still needs to be confirmed via further clinical trials.
Objectives To evaluate the expression and clinical significance of COX-2 in gastric carcinoma. Methods Such databases as PubMed, CNKI, WanFang Data and VIP were searched for the studies on the association between COX-2 and gastric carcinoma from inception to January 2017. Two researchers independently screened literature, extracted data and evaluate the risk of bias of included studies. RevMan 5.3 software were used to analyze the data. Results Eleven case-control studies involving 1 366 patients were included. The results of meta-analysis showed that, there were significant differences of COX-2 expression in the following comparisons: gastric carcinoma vs. normal esophageal tissues (RR=1.69, 95%CI 1.39 to 2.06, P<0.000 01), with serosa invasivevs. without serosa invasive (RR=1.37, 95%CI 1.14 to 1.66, P=0.001), clinical stages Ⅰ-Ⅱ vs. clinical stages Ⅲ-Ⅳ (RR=0.78, 95%CI 0.69 to 0.90, P=0.000 3), as well as lymph node metastasis vs. non-lymph node metastasis (RR=1.48, 95%CI 1.34 to 1.63, P<0.000 01). While no significant difference was found between well/general differentiation group and poorly differentiation group (RR=0.84, 95%CI 0.51 to 1.38,P=0.48). Conclusion COX-2 expression is associated with depth of invasion, clinical stage and lymph node metastasis, which prompts that COX-2 may play an important role in the occurrence and development of gastric carcinoma. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.
目的 构建沉默环氧化酶-2（COX-2）基因重组慢病毒，观察其体外侵袭的抑制作用，从而探讨干扰COX-2抑制喉癌细胞增殖的作用机理，为喉癌的治疗提供新的思路。 方法 逆转录聚合酶链反应（RT-PCR）检测COX-2基因在人表皮样喉癌细胞（Hep-2）中的表达情况。利用上海吉凯公司RNA干扰（RNAi）慢病毒表达载体系统，构建针对COX-2基因慢病毒RNAi表达载体。转染Hep-2细胞，干扰COX-2基因的表达，实时定量PCR检测干扰前后基因表达变化。利用生长曲线测定干扰载体转染前后细胞生长速度变化。流式细胞仪检测细胞的生长周期。Boyden侵袭小室法测定体外侵袭力。 结果 成功构建了COX-2慢病毒RNAi表达载体，并建立了干扰COX-2基因的Hep-2细胞系。实时定量PCR检测COX-2基因在Hep-2细胞系中过表达被显著抑制。生长曲线测定，COX-2基因干扰后细胞增殖明显变慢。流式细胞仪检测细胞的生长周期可见干扰组诱导Hep-2细胞凋亡，转染G0～G1期细胞数量明显上升，S期细胞减少，表明siRNA干扰Hep-2细胞后，细胞由G0～G1期进入到S期受到阻滞，细胞增殖速度下降。体外侵袭实验中，Hep-2-AS侵袭细胞数（31.0 ± 1.8）显著低于Hep-2细胞（104.0 ± 2.6）及Hep-2-P细胞（99.0 ± 2.7），差异有统计学意义（P＜0.05）。 结论 喉癌中过表达的COX-2基因被干扰后表达明显降低并显著抑制细胞的生长速度和侵袭能力。同时验证了COX-2基因RNA干扰在进行抗肿瘤的治疗中潜在的应用前景。
Objective To evaluate correlation between –765G>C polymorphism of cyclooxygenase-2 (COX-2) gene and susceptibility to colorectal cancer. Methods The PubMed, Embase, The Cochrane Library, CNKI, CBM, VIP, and Wanfang databases were searched from inception to May 2016 to collect case-control studies about the –765G>C polymorphism of COX-2 gene and the susceptibility to colorectal cancer. Two reviewers independently screened the literatures and extracted data of included studies. The meta-analysis was performed using Stata 12.0 software. Results A total of 13 studies involving 4 998 cases and 7 750 controls were included in this meta-analysis. The overall meta-analysis showed that all the genotypes of the –765G>C polymorphism of COX-2 gene were not associated with the susceptibility to colorectal cancer 〔GGvs. GC: OR=0.98, 95% CI (0.89, 1.07), P=0.590; GC vs. CC: OR=0.85, 95% CI (0.65, 1.11), P=0.236; GG vs. CC: OR=0.86, 95% CI (0.66, 1.12), P=0.275; GG+GC vs. CC:OR=0.87, 95% CI (0.67, 1.13), P=0.288; GG vs. GC+CC:OR=0.97, 95% CI (0.89, 1.05), P=0.425〕. The stratification analysis by ethnicity showed that, the GG vs. GC and GG vs. GC+CC modes of COX-2 gene –765G>C polymorphism might be associated with the susceptibility to colorectal cancer in Asians 〔GGvs. GC: OR=0.70, 95%CI (0.58, 0.86), P=0.001; GG vs. GC+CC: OR=0.71, 95% CI (0.58, 0.87), P=0.001〕, but the other modes were not associated with it 〔GC vs. CC: OR=1.74, 95% CI (0.61, 5.00), P=0.301; GG vs. CC: OR=1.18, 95% CI (0.40, 3.45), P=0.762; GG+GC vs. CC: OR=1.50, 95% CI (0.53, 4.23), P=0.440〕. The genotypes of the –765G>C polymorphism of COX-2 gene were not associated with the susceptibility to colorectal cancer in Caucasians 〔GGvs. GC: OR=1.05, 95% CI (0.95, 1.16), P=0.321; GC vs. CC: OR=0.80, 95% CI (0.61, 1.01), P=0.129; GG vs. CC: OR=0.85, 95% CI (0.64, 1.11), P=0.228; GG+GC vs. CC: OR=0.83, 95% CI (0.64, 1.09), P=0.198; GG vs. GC+CC: OR=1.03, 95% CI (0.94, 1.13), P=0.526〕. Conclusion Current evidence shows that –765G>C polymorphism of COX-2 gene might be a genetic risk factor for colorectal cancer in Asians, but not in Caucasians.