Objective To summarize the research progress in antitumor mechanism of non-steroidal anti-inflam-matory drugs. Methods The domestic and international published literatures about antitumor mechanism of non-steroidal anti-inflammatory drugs in recent years were reviewed. Results The antitumor mechanism of non-steroidal anti-inflam-matory drugs was multistrata and multidigit. Conclusion Non-steroidal anti-inflammatory drugs can be used to prevent the development of colorectal cancer and also be a adjuvant therapy after radical operation for colorectal cancer.
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.
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.
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.
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.
【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.
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.
【Abstract】 Objective To study the expressions of cyclooxygenase-2 (Cox-2) and angiopoietin-2 (Ang-2) in colorectal cancer tissues, cancer adjacent tissues and normal colorectal tissues, and the relationship between these expressions and the clinicopathologic features of colorectal cancer. Methods Forty-five excised samples of colorectal adenocarcinoma were confirmed pathologically and 39 of them were of well or moderately differentiated and 6 of poorly differentiated. Lymph nodes metastasis developed in 30 patients. And 15 cases were in stage of A or B and the rest were in the stage of C or D according to the Dukes stage. Taken PBS as the negative control and the verified Cox-2 or Ang-2 positive sections as positive controls, this study detected the expressions of Cox-2 and Ang-2 protein in 45 colorectal cancer tissues, 45 cancer adjacent tissues and 15 normal colorectal tissues by using immunohistochemical SP technique method. Results Cox-2 and Ang-2 were expressed in colorectal cancer tissues and cancer adjacent tissues, but were not expressed in normal colorectal tissues. In 45 colorectal cancer tissues, the positive expression rates of Cox-2 and Ang-2 were 80.0% and 66.7%; in 45 cancer adjacent tissues, the positive expression rates of Cox-2 and Ang-2 were 35.6% and 11.1%, respectively. The positive expression rates of both Cox-2 and Ang-2 in colorectal cancer tissues were significantly higher than those in cancer adjacent and normal colorectal tissues. There were close correlations between the expressions of Cox-2 and Ang-2 and some pathologic features, such as lymph node metastasis and Dukes stage; whereas there were no significant association between the expressions and gender, histological type and position of tumor. There was also a close correlation between the expressions of Cox-2 and Ang-2 themselves. Conclusion Cox-2 and Ang-2 play an important role in the occurrence and development of colorectal cancer. The use of specific inhibitor of Cox-2 as a treatment for colorectal cancer may become feasible and necessary.
