Cyclooxygenase-2

环氧合酶 - 2
  • 文章类型: Journal Article
    COX-2基因的单核苷酸多态性,也被称为PTGS2,它编码一种促炎因子环氧合酶-2,改变发生多种肿瘤的风险,但是这些发现对于肺癌并不一致。我们先前报道纯合COX-2-1195A基因型与日本人慢性阻塞性肺疾病(COPD)的风险增加有关。由于对香烟烟雾的遗传易感性,COPD是肺癌的重要危险因素。在这项研究中,我们调查了日本人群中COX-2-1195G/A多态性与肺癌易感性之间的关系.我们使用聚合酶链反应-限制性片段长度多态性测定法评估了330例新诊断的肺癌患者和162例健康对照的COX-2-1195G/A的基因型分布。我们的结果表明,COX-2-1195G/A多态性与患肺癌的风险之间没有关系。然而,与对照组相比,纯合COX-2-1195A基因型增加肺鳞状细胞癌的风险(比值比=2.902;95%置信区间,1.171-7.195;p=0.021),而未观察到与腺癌风险相关。此外,Kaplan-Meier分析表明,纯合子COX-2-1195A的基因型分布与肺鳞癌患者的总体生存率无关。因此,我们得出的结论是,在日本个体中,纯合COX-2-1195A基因型增加了患肺鳞状细胞癌的风险,可作为早期发现肺鳞状细胞癌的预测因子.
    The single nucleotide polymorphisms of COX-2 gene, also known as PTGS2, which encodes a pro-inflammatory factor cyclooxygenase-2, alter the risk of developing multiple tumors, but these findings are not consistent for lung cancer. We previously reported that the homozygous COX-2 -1195A genotype is associated with an increased risk for chronic obstructive pulmonary disease (COPD) in Japanese individuals. COPD is a significant risk factor for lung cancer due to genetic susceptibility to cigarette smoke. In this study, we investigated the association between COX-2 -1195G/A polymorphism and lung cancer susceptibility in the Japanese population. We evaluated the genotype distribution of COX-2 -1195G/A using a polymerase chain reaction-restriction fragment length polymorphism assay for 330 newly diagnosed patients with lung cancer and 162 healthy controls. Our results show that no relationship exists between the COX-2 -1195G/A polymorphism and the risk of developing lung cancer. However, compared to the control group, the homozygous COX-2 -1195A genotype increased the risk for lung squamous cell carcinoma (odds ratio = 2.902; 95% confidence interval, 1.171-7.195; p = 0.021), whereas no association is observed with the risk for adenocarcinoma. In addition, Kaplan-Meier analysis shows that the genotype distribution of homozygous COX-2 -1195A does not correlate with the overall survival of patients with lung squamous cell carcinoma. Thus, we conclude that the homozygous COX-2 -1195A genotype confers an increased risk for lung squamous cell carcinoma in Japanese individuals and could be used as a predictive factor for early detection of lung squamous cell carcinoma.
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  • 文章类型: Case Reports
    背景:盆腔脂肪瘤病(PL)是一种罕见的良性疾病,具有组织学上良性脂肪的特征性过度生长以及盆腔器官的侵袭和压迫,通常导致非特异性下尿路症状(LUTS)。大约40%的PL患者患有腺性膀胱炎(CG)。PL与CG结合的原因知之甚少,目前尚无有效的治疗方法。难治性CG伴上尿路梗阻甚至需要部分或根治性膀胱切除术。
    方法:在这种情况下,一名患有PL伴CG的患者通过经尿道膀胱肿瘤切除术(TUR-BT)和口服塞来昔布治疗,选择性环氧合酶-2(COX-2)抑制剂。LUTS缓解了,膀胱镜检查结果明显改善。免疫组织化学显示TUR-BT样品的上皮中COX-2表达上调,提示COX-2可能参与PL合并CG的病理生理过程。
    结论:我们首次报道塞来昔布可能是PL合并难治性CG的有效治疗策略。
    BACKGROUND: Pelvic lipomatosis (PL) is a rare benign condition with characteristic overgrowth of histologically benign fat and invasion and compression of pelvic organs, often leading to non-specific lower urinary tract symptoms (LUTS). Approximately 40% of patients with PL have cystitis glandularis (CG). The cause of PL combined with CG is poorly understood, and there is currently no effective treatment. Refractory CG with upper urinary tract obstruction even requires partial or radical bladder resection.
    METHODS: In this case, a patient suffering from PL with CG was treated by transurethral resection of bladder tumour (TUR-BT) and oral administration of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor. The LUTS were alleviated, and the cystoscopy results improved significantly. Immunohistochemistry showed up-regulated COX-2 expression in the epithelium of TUR-BT samples, suggesting that COX-2 may participate in the pathophysiological process of PL combined with CG.
    CONCLUSIONS: We report for the first time that celecoxib may be an effective treatment strategy for PL combined with refractory CG.
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  • 文章类型: Journal Article
    UNASSIGNED: The association between cyclooxygenase-2 (COX-2) gene polymorphisms and hepatocellular carcinoma (HCC) has been widely reported, but the results are still controversial. To clarify the effect of COX-2 -1195G/A (rs689466), -765G/C (rs20417), and +8473T/C (rs5275) polymorphisms on HCC risk, a meta-analysis was performed.
    UNASSIGNED: The PubMed, Embase, Cochrane Library, Web of Science, Chinese BioMedical Literature, Wanfang, and Chinese National Knowledge Infrastructure databases were systematically searched to identify potential studies published up to October 10, 2014. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association. A total of eight studies with 2060 HCC cases and 2610 controls for -1195G/A, six studies with 1295 cases and 2193 controls for -765G/C, and four studies with 1477 cases and 1747 controls for +8473T/C were included in this meta-analysis.
    UNASSIGNED: Overall, the COX-2 -1195G/A, and +8473T/C polymorphisms were both significantly associated with an increased risk of HCC (rs689466 GA + AA vs. GG: OR = 1.390, P = 0.006, 95% CI: 1.099-1.759, I2 = 50.7%, Pheterogeneity = 0.048; rs5275 CC vs. TT + TC: OR = 1.484, P = 0.041, 95% CI: 1.017-2.165, I2 = 0.0%, Pheterogeneity = 0.416). In the subgroup analyses stratified by ethnicity, the COX-2 -1195G/A, -765G/C, and +8473T/C were all associated with an increased HCC risk in Asian populations (rs689466 A vs. G: OR = 1.346, P = 0.001, 95% CI: 1.137-1.595, I2 = 0.0%, Pheterogeneity = 0.869; rs20417 CC vs. GG + GC: OR = 3.069, P = 0.013, 95% CI: 1.265-7.447; rs5275 CC vs. TT + TC: OR = 1.626, P = 0.020, 95% CI: 1.079-2.452, I2 = 0.0%, Pheterogeneity = 0.495).
    UNASSIGNED: Our meta-analysis suggests that -1195G/A, -765G/C, and +8473T/C in COX-2 may contribute significantly to HCC risk.
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    文章类型: Journal Article
    The current meta-analysis incorporating 15 case-control studies involving 4,138 cases and 4,269 controls was performed on the basis of a systematical search in electronic databases for a more precise estimation on the associations of three common polymorphisms -765 G>C (rs20417), -1195G>A (rs689466) and +8473 C>T (rs5275) in Cyclooxygenase-2 (Cox-2) gene with the susceptibility to bladder cancer. The results showed that there was a significant association between rs5275 polymorphism and bladder cancer risk (C vs. T; OR=0.84; CC vs. TT: OR=0.76), especially among Chinese (CC vs. TC+TT: OR=0.48) and American (C vs. T; OR=0.83; TC vs. TT: OR=0.73; CC+TC vs. TT: OR=0.73). and the rs20417 polymorphism was significantly associated with an increased risk of bladder cancer among Chinese (C vs. G: OR=1.46; GC vs. GG: OR=1.49; CC+GC vs. GG: OR=1.51) and Indian (GC vs. GG: OR=1.63; CC+GC vs. GG: OR=1.46), but a reduced risk among American (C vs. G: OR=0.81; GC vs. GG: OR=0.76; CC+GC vs. GG: OR=0.76). Additionally, we found that the rs689466 polymorphism was associated with a decreased risk of bladder cancer in Indian (GA vs. GG: OR=0.68; AA vs. GG: OR=0.39).The present meta-analysis suggests that Cox-2 rs5275 polymorphism may contribute to the risk of bladder cancer, particularly among Chinese and American. The rs20417 polymorphism may play a protective role in the development of bladder cancer in Indian and Chinese but act as a risk factor among American, while the rs689466 polymorphism was more likely to be associated with a decreased risk of bladder cancer in Indian.
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  • 文章类型: Journal Article
    BACKGROUND: Coal workers\' pneumoconiosis (CWP) is characterized by progressive pulmonary fibrosis. Inflammation is crucial in the host response to silica and it contributes to pulmonary fibrosis. Cyclooxygenase-2 is involved in this process. The association between single-nucleotide polymorphisms in cyclooxygenase-2 gene with pneumoconiosis risk was investigated.
    METHODS: An association study was conducted by analyzing two single-nucleotide polymorphisms of cyclooxygenase-2 (rs689466 and rs20417) in a case-control study involving 90 patients and 90 healthy individuals (controls). Genotyping was performed by the TaqMan method.
    RESULTS: The rs689466 AG and GG and rs689466 GC polymorphisms were significantly less frequent in patients than in controls. Cyclooxygenase-2 rs689466 and rs20417 variant genotypes exhibited 21% and 12% decreased CWP risk, respectively.
    CONCLUSIONS: Cyclooxygenase-2 rs689466 and rs20417 polymorphisms were associated with CWP risk.
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  • 文章类型: Journal Article
    OBJECTIVE: Cyclooxygenase-2 (COX-2) enzyme is a major mediator of inflammation in periodontitis, leading to loss of gingival tissues and alveolar bone supporting the teeth. Previous studies have explored the role of COX-2 polymorphisms with the risk of periodontitis in different ethnic groups; however, findings are inconsistent. So, we aimed to investigate the association of COX-2 polymorphisms (rs20417, rs689466, and rs5275) in susceptibility to chronic periodontitis (CP) in northern Indian population. Meta-analysis was also carried out to precisely estimate the effect of COX-2 polymorphisms in CP.
    METHODS: Genotyping of COX-2 polymorphisms was carried out through PCR-RFLP in 200 CP cases and 200 controls. For risk estimation, binary logistic regression was applied using SPSS, version 15.0, while meta-analysis was carried using MIX 2.0 software.
    RESULTS: None of the COX-2 polymorphisms independently were associated with the risk of CP. Meta-analysis suggested a significant reduced risk of CP with rs5275+8473 C allele and rs20417 in Chinese population.
    CONCLUSIONS: No association was observed in any of the studied COX-2 polymorphisms with CP in North India. But, the study should be replicated in larger sample size to arrive at a definitive conclusion. Meta-analysis suggested a role of rs5275 COX-2 polymorphisms in susceptibility to overall CP, and on ethnic basis, rs20417 showed reduced risk of CP in Chinese population.
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  • 文章类型: Journal Article
    The objective was to measure the impact of exposure to coxibs and non-steroidal antiinflammatory drugs (NSAID) on morbidity and mortality in older patients with acute myocardial infarction (AMI). A nested case-control study was carried out using an exhaustive population-based cohort of patients aged 66 years and older living in Quebec (Canada) who survived a hospitalization for AMI (ICD-9 410) between 1999 and 2002. The main variables were all-cause and cardiovascular (CV) death, subsequent hospital admission for AMI, and a composite end-point including recurrent AMI or CV death. Conditional logistic regressions were used to estimate the risk of mortality and morbidity. A total of 19,823 patients aged 66 years and older survived hospitalization for AMI in the province of Quebec between 1999 and 2002. After controlling for covariables, the risk of subsequent AMI and the risk of composite end-point were increased by the use of rofecoxib. The risk of subsequent AMI was particularly high for new rofecoxib users (HR 2.47, 95% CI 1.57-3.89). No increased risk was observed for celecoxib users. No increased risk of CV death was observed for patients exposed to coxibs or NSAIDs. Patients newly exposed to NSAIDs were at an increased risk of death (HR 2.22, 95% CI 1.30-3.77) and of composite end-point (HR 2.28, 95% CI 1.35-3.84). Users of rofecoxib and NSAIDs, but not celecoxib, were at an increased risk of recurrent AMI and of composite end-point. Surprisingly, no increased risk of CV death was observed. Further studies are needed to better understand these apparently contradictory results.
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