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.
Objective To investigate the relationship between cyclooxygenase-2 (COX-2) gene polymorphism and genetic susceptibility to esophageal cancer. Methods The PubMed and EMbase databases were searched from the date of their establishment to January 1st, 2011 to collect the case-control studies on COX-2 polymorphism and susceptibility to esophageal cancer. For the population genotype distributions of both esophagus cancer group and control group, their odds ratios (ORs) and 95% confidence intervals (CIs) were taken as the effect indexes, either the fixed or random effect model was applied to conducted Meta-analysis in homozygote comparison, dominant and recessive genetic models, and the publication bias was assessed then. All statistical analyses were conducted with Stata11.0 software. Results A total of five case-control studies were included. The results of meta-analyses showed for the COX-2-765Ggt;C polymorphism, the CC+GC genotype was associated with the risk of esophageal cancer in a dominant genetic model (CC+GC vs. GG: OR=1.806, 95% CI 1.050 to 3.106); for the COX-2-1195Ggt;A polymorphism, the AA genotype was associated with the risk of esophageal cancer in homozygote comparison and recessive genetic models, the AA+GA genotype was associated with the risk of esophageal cancer in a dominant genetic model. Conclusion It is suggested that COX-2 polymorphism may be associated with genetic susceptibility to esophageal 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.
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 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 investigate the efficacy of sequential treatment with adductor canal nerve block (ACNB) and cyclooxygenase 2 (COX-2) selective inhibitor (parecoxib and celecoxib) after primary total knee arthroplasty (TKA). MethodsBetween January 2015 and December 2015, 90 osteoarthritis patients who met the inclusion criteria were treated, and randomly divided into 3 groups:ACNB+COX-2 group (group A, n=30), COX-2 group (group B, n=30), and control group (group C, n=30). There was no significant difference in gender, age, body mass index, side, and osteoarthritis duration between groups (P > 0.05), and the data were comparable. ACNB was used in group A at the end of TKA. Intravenous injection of parecoxib (40 mg per 12 hours) was administrated at the first three postoperative days, and followed by oral celecoxib (200 mg per 12 hours) until 6 weeks after operation in groups A and B; while placebo was given at the same time point in group C. Oral tramadol or intravenous morphine, as remedial measures, were introduced when patients had a visual analogue scale (VAS) score more than 4. The following indicators were compared between groups:the operative time, drainage volume at 24 hours after operation, length of hospital stay, and incidence of side effect; VAS pain scores, morphine consumption, range of motion (ROM) of the knee joint, and inflammatory cytokines levels at pre-operation and at 1 day, 2 days, 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks after operation; morphine consumption within first 24 hours and at 24 hours to 6 weeks after operation; the American Hospital for Special Surgery (HSS) score at 1, 2, 4, and 6 weeks after operation; and the serum coagulation parameters at pre-operation, and at 1, 3, and 14 days after operation. ResultsThe length of hospital stay was significantly shorter and the incidence of postoperative nausea and vomiting was significantly lower in groups A and B than group C (P < 0.05). The VAS scores at rest (VASR) of groups A and B were significantly lower than that of group C at 1, 2, and 3 days after operation (P < 0.05); difference in the VAS scores at walking (VASW) was significant between groups at 1 day after operation (P < 0.05), and group A had the lowest VASW; and the VASW of groups A and B were significantly lower than that of group C at 2 and 3 days and at 1, 2, 4, and 6 weeks after operation (P < 0.05). The difference in morphine consumption was significant between groups within the first 24 hours after operation (P < 0.05), and group A exhibited the lowest consumption; and the morphine consumption in groups A and B was significantly lower than that in group C at 24 hours to 6 weeks after operation (P < 0.05). Significant difference was found in HSS scores between groups at 1, 2, 4, and 6 weeks after operation, and group A showed the highest score (P < 0.05). At 1 and 2 days after operation, group A showed the highest ROM (P < 0.05), and ROM of groups A and B was significantly higher that of group C at 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks after operation (P < 0.05). Groups A and B were significantly lower than group C in the serum erythrocyte sedimentation rate at 2 days, 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks, in C-reactive protein levels at 1, 2, and 3 days, in interleukin 6 (IL-6) and TNF-α levels at 1 day to 6 weeks, and in IL-8 level at 2 and 3 days (P < 0.05). The drainage volume within the first 24 hours and the serum coagulation parameters within the 2 weeks after operation showed no significant difference between groups (P > 0.05). ConclusionSequential treatment with ACNB and COX-2 selective inhibitor is a safe and effective approach for postoperative pain management after primary TKA, and it can alleviate postoperative pain, promote the joint function recovery, and reduce the risk of adverse reactions.
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.