环氧化酶-2与肺癌

环氧化酶-2（ cyclooxygenase-2, COX-2 ）是环氧化酶的诱导型,在肺癌及其转移灶中高表达,以多环节参与肺癌的发生发展,且与肺癌患者的预后有关。COX-2抑制剂的临床应用有预防和抑制肺癌的作用。     

胃癌中环氧化酶-2的研究进展

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环氧化酶-2抑制剂在肺癌治疗中的研究进展

现已证实,环氧化酶2（COX-2）不仅参与炎症反应,在各种恶性肿瘤亦有不同程度的表达。目前许多临床前期实验皆证实COX-2通过多种致癌机制在肺肿瘤的发生、发展、转移和预后扮演很重要的角色。因此,COX-2抑制剂为当前研究治疗肺癌的新靶点之一。现国外学者已针对COX-2抑制剂在肺癌治疗的应用进行临床实验。本文就COX-2与肺癌的关系和COX-2抑制剂在肺癌临床应用中的研究进展综述如下。     

环氧合酶-2与胃癌

环氧合酶(COX)是合成前列腺素(PG)过程中一个重要的限速酶,有COX-1和COX-2两种异构体.近年来的研究表明,COX-2与多种肿瘤的发生发展密切相关.此文就COX-2与胃癌的关系以及COX-2抑制剂治疗胃癌的研究进展作一综述.     

环氧化酶-2基因多态性与回族人群胃癌易感性的关联

目的: 探讨环氧化酶-2(COX-2)-765G>C的单核昔酸多态性与回族人群胃癌易感性的关系.方法: 以PCR-限制性片段长度多态性方法对回族人群中胃癌组( n = 100)、癌前病变组( n =102)和正常对照组( n = 105)进行基因分型. 使用ELISA法检测H pylori感染.结果: COX-2-765GC+CC在胃癌组显著增高( P = 0.021). 交互作用分析显示: 食腌菜的-765GC+CC携带者患胃癌的风险是不食腌菜的-765GG携带者的5.038倍( P = 0.000);H pylori感染阳性的-765GC+CC携带者患胃癌的风险是H pylori感染阴性-765 GG携带者的3.520倍( P = 0.002).结论: COX-2-765G>C和中国甘肃地区回族人群胃癌易感性增高相关. -765 GC+CC分别与食腌菜、H pylori感染在胃癌的发病风险中存在着加乘交互效应.     

环氧化酶-2及其抑制剂与Barrett食管和食管癌关系的研究进展

环氧化酶(COX)是花生四烯酸合成前列腺素(PG)过程中一个重要的限速酶。普遍认为COX-1为生理酶,由它产生的PG参与机体正常生理过程和保护功能,如保护胃肠黏膜完整性、调节血小板功能和脏器血流。而COX-2在生理情况下几乎不表达,在许多促炎症和致突变因素的刺激下,COX-2可被诱导出来,表现在炎症部位的巨噬、滑膜和内皮等细胞,参与病理过程,它产生PG参与炎症反应。已有的研究结果表明,COX-2与Barrett食管(Bar-rett’s esophagus)的癌变,食管癌的发生、发展有着密切关系。现就其研究进展综述如下。1 COX-2在Barrett食管、食管癌中的…     

环氧化酶-2在胃癌和胃炎中的表达及其与幽门螺杆菌感染的关系

目的探讨环氧化酶-2（Cyclooxygense-2，COX-2）在胃癌和胃炎中的表达及其与幽门螺杆菌（Helicobacter pylori，Hp）感染的关系，为胃癌的预防和治疗提供有价值的实验和理论依据。方法采用免疫组化技术检测COX-2、Hp在胃癌以及各型胃炎中的表达。结果胃癌和萎缩性胃炎伴不典型增生组织中COX-2的表达率明显高于浅表性胃炎（P〈0.05），COX-2在Hp感染阳性萎缩性胃炎伴不典型增生病人中的表达率明显高于Hp感染阴性组（P〈0．05），高、中分化胃癌COX-2表达率高于低分化胃癌（P〈0．05）。结论COX-2在胃癌组织中存在过表达，Hp感染可使萎缩性胃炎伴不典型增生组织中COX-2表达增强，COX-2表达与胃癌分化程度有关。     

环氧化酶—2与肺癌

环氧化酶-2(COX-2)是内源性前列腺素(PGs)合成中的限速酶。它通过多种途径参与肺癌的发生发展和转移，并与肺癌患者的预后有关。一些体内外研究表明COX-2抑制剂能够抑制肺癌细胞的生长与转移临床上选择性COX-2抑制剂有可能成为肺癌预防和化学治疗的新靶点。     

环氧化酶-2与肺癌

环氧化酶 2 (COX 2 )是内源性前列腺素 (PGs)合成中的限速酶。它通过多种途径参与肺癌的发生、发展和转移 ,并与肺癌患者的预后有关。一些体内外研究表明COX 2抑制剂能够抑制肺癌细胞的生长与转移。临床上选择性COX 2抑制剂有可能成为肺癌预防和化学治疗的新靶点     

环氧化酶-2抑制剂对非小细胞肺癌抗肿瘤作用机制的研究进展

肺癌目前位于全世界癌症死因的首位,约占全部恶性肿瘤的19％。每年约有超过100万人死于肺癌,严重威胁着人类的健康和生命。其中,非小细胞肺癌约占80％～85％。研究显示环氧化酶-2（cycl00xygenase-2,COX-2）在非小细胞肺癌组织中表达上调,并且与肿瘤细胞的增殖、侵袭和远处转移有关。近年来COX-2抑制剂在非小细胞肺癌治疗中的作用日益受到关注。特异性COX～2抑制剂（尼美舒利、塞来昔布、罗非昔布、NS398等）和非特异性COX-2抑制剂（吲哚美辛、布洛芬等）对非小细胞肺癌均有抗肿瘤作用,可增加非小细胞肺癌化疗及放疗的敏感性。实验研究表明COX-2抑制剂可抑制非小细胞肺癌细胞的增殖,诱导细胞的凋亡,抑制肿瘤新生血管的生成,抑制肿瘤远处转移等。国外临床研究表明COX-2抑制剂可提高化疗药物的临床疗效,并减弱化疗不良反应。COX-2抑制剂显著的抗肿瘤作用为非小细胞肺癌的治疗带来了新的曙光。     

Mechanism and clinical significance of cyclooxygenase-2 expression in gastric cancer

AIM: To determine the correlation between methylation status of 5' CpG island of cyclooxygenase-2 (COX-2) gene and protein expression in gastric cancer tissues for distinguishing the molecular characters of gastric cancers. METHODS: Methylation status of 5' CpG island of COX-2 gene was studied by PCR amplification after HpaⅡ and Hha I restrictive enzyme digestion;COX-2 expression was evaluated by immunohistochemical method. RESULTS: Hpa Ⅱ and HhaI site were all methylated in 12 normal gastric mucosa tissues, whereas they were demethylated in 77.27% (34/44) and 84.09% (37/44) gastric cancer tissues,respectively.Expression of COX-2 was detected in 68.18% (30/44) gastric cancer tissues, but no expression was found in normal gastric mucosa tissues. In gastric cancer tissues, COX-2 expression was correlated significantly with HpaⅡ site demethylation (29/30 vs 5/14, P<0.001 and HhaI site demethylation (28/30 vs 9/14,P<0.05). CONCLUSION: The demethylation of 5' CpG island of gene is necessary for COX-2 expression in human gastric cancer. The expression status of COX-2 may provide theoretical basis for COX-2 targeting gastric cancer treatments.     

Role of cyclooxygenase-2 in gastric cancer development and progression

Although the incidence of gastric cancer has been declining in recent decades,it remains a major public health issue as the second leading cause of cancer death worldwide.In China,gastric cancer is still the main cause of death in patients with malignant tumors.Most patients are diagnosed at an advanced stage and mortality is high.Cyclooxygenase-2(COX-2)is a ratelimiting enzyme in prostanoid synthesis and plays an important role in the development and progression of gastric cancer.The expression of COX-2 in gastric cancer is upregulated and its molecular mechanisms have been investigated.Helicobacter pylori infection,tumor suppressor gene mutation and the activation of nuclear factor-kappa B may be responsible for the elevated expression of COX-2 in gastric cancer.The mechanisms of COX-2 in the development and progression of gastric cancer are probably through promoting the proliferation of gastric cancer cells,while inhibiting apoptosis,assisting angiogenesis and lymphatic metastasis,and participating in cancer invasion and immunosuppression.This review is intended to discuss,comment and summarize recent research progress on the role of COX-2 in gastric cancer development and progression,and elucidate the molecular mechanisms which might be involved in the carcinogenesis.     

Interaction between cyclooxygenase-2,Snail,and E-cadherin in gastric cancer cells

AIM:To investigate the mechanisms of how cyclooxygenase-2(COX-2)regulates E-cadherin in gastric cancer cells.METHODS:COX-2 expression in human gastric cancer cell lines SGC-7901,BGC-823,MGC-803 and AGS were measured at the mRNA and protein level.COX-2 rich cell line SGC-7901 was chosen for subsequent experiments.siRNA mediated gene knockdown was used to investigate the impact of COX-2 on nuclear factor-κB (NF-κB),Snail,and E-cadherin in gastric cancer cells.Gene expression was determined by Western blot and real-time polymerase chain reaction.To analyze whether NF-κB inhibition could interrupt the modulatory effect of COX-2 or prostaglandin E2(PGE2)on E-cadherin,gastric cancer cells were treated with celecoxib or PGE2,in the presence of NF-κB specific siRNA.RESULTS:Highest expression level of COX-2 was found in SGC-7901 cells,both at mRNA and protein levels.siRNA mediated down-regulation of COX-2 led to a reduced expression of NF-κB and Snail,but an increased expression of E-cadherin in SGC-7901 cells.siRNA mediated down-regulation of NF-κB also led to a reduced expression of E-cadherin and Snail in SGC-7901 cells.However,COX-2 expression did not alter after cells were treated with NF-κB specific siRNA in SGC-7901 cells.Treatment of SGC-7901 cells with celecoxib led to a reduced expression of Snail but an increased expression of E-cadherin.In contrast,treatment of SGC-7901 cells with PGE2 led to an increased Snail and a decreased E-cadherin.However,siRNAmediated knockdown of NF-κB partially abolished the effect of celecoxib and PGE2 on the regulation of E-cadherin and Snail in SGC-7901 cells.CONCLUSION:COX-2 likely functions upstream of NF-κB and regulates the expression of E-cadherin via NF-κB/Snail signaling pathway in gastric cancer cells.     

胃癌及非癌组织中环氧合酶-2和人胃癌相关MG7抗原表达及意义

目的 研究胃癌中环氧合酶-2(COX-2)和人胃癌相关抗原(MG7-Ag)表达的相关性及意义。方法 采用ABC免疫组化法检测l00例藏族胃癌手术患者癌组织及其相应非癌组织和部分远处脏器转移灶中COX-2和MG7-Ag的表达；用甲苯胺蓝染色和改良Giemsa染色法同时检测胃癌组织中幽门螺杆菌(Hp)感染状况。结果胃癌中C0X9-2和MG7-Ag的阳性检出率分别为88．0％和92．0％；在非癌组织中COX-2和MG7-Ag的阳性检出率从慢性浅表性胃炎、慢性萎缩性胃炎、肠上皮化生到不典型增生均呈递增趋势；伴淋巴结和远处脏器转移的胃癌中COX-2的阳性表达率高于无淋巴结转移(P＜0．05)和无远处脏器转移的胃癌组织(P＜0．05)；4l例Hp阳性胃癌组织中COX-2阳性表达率明显高于Hp阴性的胃癌组织(P＜0．05)；COX-2和MG7-Ag在胃癌中的表达呈正相关(r=0．48，P＜0．01)。结论 COX-2与MG7-Ag可能在胃癌的演进过程中起着既独立又相瓦协同的作用。     

环氧合酶-2在胰腺癌治疗中的作用

在众多实体瘤中,胰腺癌的预后最差,炎症是其发展过程中的重要影响因素。环氧合酶-2（COX-2）在大多数胰腺癌中高表达并调控其发生发展过程。COX-2在肿瘤细胞生成、凋亡、血管生成方面有着重要作用,因此它是治疗胰腺癌极好的分子靶点。大量的实验证明阻滞COX-2的表达对治疗胰腺癌有良好的效果,治疗方法主要包括COX-2抑制剂、基因治疗、抗氧化剂、生长因子受体抑制剂、生物碱等。本综述主要讨论各种治疗方法的应用和不足,总结COX-2在胰腺癌治疗中的作用。     

Increased expression of cyclooxygenase-2 in first-degree relatives of gastric cancer patients

AIM: To study the expression of cydooxygenase-2 (COX-2) in human gastric cancer tissues and their paired adjacent mucosa, as well as mucosa from gastric antrum and corpus of the first-degree relatives of the recruited cancer patients. METHODS: The expression of COX-2 mRNA in 38 patients with gastric cancer and their 29 first-degree relatives and 18 healthy controls was assessed by the real time RT-PCR. The expression of COX-2 protein was determined by Western blot. RESULTS: A marked increase in COX-2 mRNA expression was found in 20 of 37 (54%) cancerous tissues compared to their respective paired normal mucosa (P<0.001). Interestingly, increased COX-2 mRNA expression was also found in mucosa of the corpus (6/29) and antrum (13/29) of their first-degree relatives. Increased COX-2 mRNA expression was more frequently observed in the antrum biopsies from cancer patients than in the antrum biopsies from healthy controls (P<0.05). In addition, 3 of 23 (13%) patients with atrophic mucosa and 6 of 35 (17%) patients with intestinal metaplasia showed increased COX-2 mRNA expression. Furthermore, COX-2 expression increased in H pylori-positive tissues, especially in antrum mucosa. CONCLUSION: Increased COX-2 expression is involved in gastric carcinogenesis, and may be necessary for maintenance of the malignant phenotype and contribute to Helicobacter pylori-associated malignant transformation.     

Genetic variant of cyclooxygenase-2 in gastric cancer: More inflammation and susceptibility

Gastric cancer accounts for the majority cancer-related deaths worldwide. Although various methods have considerably improved the screening, diagnosis, and treatment of gastric cancer, its incidence is still high in Asia, and the 5-year survival rate of advanced gastric cancer patients is only 10%-20%. Therefore, more effective drugs and better screening strategies are needed for reducing the incidence and mortality of gastric cancer. Cyclooxygenase-2 (COX-2) is considered to be the key inducible enzyme in prostaglandins (PGs) synthesis, which is involved in multiple pathways in the inflammatory response. For example, inflammatory cytokines stimulate innate immune responses via Toll-like receptors and nuclear factor-kappa B to induce COX-2/PGE2 pathway. In these processes, the production of an inflammatory microenvironment promotes the occurrence of gastric cancer. Epidemiological studies have also indicated that non-steroidal anti-inflammatory drugs can reduce the risk of malignant tumors of the digestive system by blocking the effect of COX-2. However, clinical use of COX-2 inhibitors to prevent or treat gastric cancer may be limited because of potential side effects, especially in the cardiovascular system. Given these side effects and low treatment efficacy, new therapeutic approaches and early screening strategies are urgently needed. Some studies have shown that genetic variation in COX-2 also play an important role in carcinogenesis. However, the genetic variation analysis in these studies is incomplete and isolated, pointing out only a few single nucleotide polymorphisms (SNPs) and the risk of gastric cancer, and no comprehensive study covering the whole gene region has been carried out. In addition, copy number variation (CNV) is not mentioned. In this review, we summarize the SNPs in the whole COX-2 gene sequence, including exons, introns, and both the 5’ and 3’ untranslated regions. Results suggest that COX-2 does not increase its expression through the CNV and the SNPs in COX-2 may serve as the potential marker to establish risk stratification in the general population. This review synthesizes emerging insights of COX-2 as a biomarker in multiple studies, summarizes the association between whole COX-2 sequence variation and susceptibility to gastric cancer, and discusses the future prospect of therapeutic intervention, which will be helpful for early screening and further research to find new approaches to gastric cancer treatment.     

Role of cyclooxygenase-2 in the carcinogenesis of gastrointestinal tract cancers： A review and report of personal experience

Selective cyclooxygenase (COX)-2 inhibitors (coxibs) were developed as one of the anti-inflammatory drugs to avoid the various side effects of non-steroidal anti-inflammatory drugs (NSAIDs). However, coxibs also have an ability to inhibit tumor development of various kinds the same way that NSAIDs do. Many experimental studies using cell lines and animal models demonstrated an ability to prevent tumor proliferation of COX-2 inhibitors. After performing a randomized study for polyp chemoprevention study in patients with familial adenomatous polyposis (FAP), which showed that the treatment with celecoxib, one of the coxibs, significantly reduced the number of colorectal polyps in 2000, the U.S. Food and Drug Administration (FDA) immediately approved the clinical use of celecoxib for FAP patients. However, some coxibs were recently reported to increase the risk of serious cardiovascular events including heart attack and stroke. In this article we review a role of COX-2 in carcinogenesis of gastrointestinal tract, such as the esophagus, stomach and colorectum, and also analyze the prospect of coxibs for chemoprevention of gastrointestinal tract tumors.