环氧化酶-2在胃癌中的作用研究进展

体外研究证实,COX抑制剂作为单一药物可能有预防肿瘤发生的作用。同样的,环氧化酶（COX）抑制剂或非甾体抗炎药（NSAID,如阿司匹林）能够减少恶性肿瘤的发生和发展,但关于COX抑制剂抗肿瘤的作用机制还需要更加深入的研究。在此,我们将COX-2在肿瘤中的作用及COX-2抑制剂抗肿瘤的可能作用机制综述如下：     

新型非甾体类消炎药治疗消化道肿瘤研究进展

大量的实验室资料及流行病学资料表明非甾体类消炎药（NSAIDs）对消化道肿瘤具有防治作用。其可能的机制如下：（1）抑制环氧合酶-2(COX-2)的活性和前列腺素（PGs）的合成；（2）诱导细胞凋亡；（3）其它机制如下：抑制转录因子核因子KB(Nuclear Factor-KB，NF-KB)、抑制幽门螺杆菌、改变细胞周期及激活三叶肽等。近年来，开发出了更为安全有效的新型非甾体类消炎药，有望应用于临床消化道肿瘤的化学预防及化学治疗。     

非甾体抗炎药肾损害

非甾体抗炎药（NSAIDs）通过抑制环氧化酶（cyclooxygenase，COX），减少前列腺素（pG）的产生而发挥作用，具有抗炎、解热、镇痛等作用，因此，在发热、疼痛以及风湿性疾病等疾病的治疗中广泛应用。按照对环氧化酶的两种异构酶（COX-1和COX-2）的作用特性，可将NSAIDs分为传统的NSAIDs和选择性COX-2抑制剂两大类。     

非甾体抗炎药在消化系肿瘤中的应用

非甾体抗炎药(NSAIDs)为常用的解热镇痛剂,临床应用已有100多年的历史。70年初,发现阿斯匹林(aspirin)等NSDIDs具有抑制前列腺素(PG)合成及抗肿瘤作用,随后对此进行了较广泛的研究,并取得了一定成绩。本文综述NSAIDs在消化系肿瘤中的实验研究与临床应用。一、NSAIDs的抗肿瘤作用机理环氧化酶(COX)是催化花生四烯酸产生的关键限速酶,     

COX-2抑制剂在消化道肿瘤防治中的研究进展

环氧合酶(cyclooxygenase，COX)是前列腺素(PGs)合成过程中的一个重要限速酶，目前发现其主要存在两种亚型：COX-1和COX-2。近年来研究发现COX-2与消化系肿瘤关系密切，其不仅在消化道肿瘤中有较高表达，并可能参与肿瘤的增殖、转移及分化。传统的非甾体类消炎药(NSAIDs)和COX-2抑制剂均已被证实可防治结肠癌、胃癌和家族性结肠息肉病的发生、发展，因而COX-2抑制剂很可能作为预防和辅助治疗消化道肿瘤的重要药物。     

美洛昔康治疗类风湿关节炎的疗效观察与评价

类风湿关节炎（rheumatoid arthritis,RA）是一种主要累及外周关节的多系统、炎症性自身免疫疾病。流行病学的调查结果证实风湿病愈来愈成为影响人们健康的主要疾病之一。目前治疗RA主要使用以下四类药物：非甾体类抗炎药（Non—steroidal anti—inflammatory drugs,NSAIDs）、改善病情的慢作用抗风湿药（DMABDs）、糖皮质激素和植物药。NSAIDs因抑制环氧化酶（COX）而达到镇痛抗炎的效果。     

环氧化酶-2与鼻咽癌的研究进展

环氧化酶（cyclooxygenase，cox）是人体内催化花生四烯酸转化为前列腺素（prostaglandins，PGS）的一种关键酶，细胞内的花生四烯酸在COX催化下形成垂体生长激素2（PGH2）。然后PGH2又在相应PG异构酶作用下合成PGE、PGF、PGD、PGI等新生物，这些新生物中，现在已肯定PGE2与肿瘤的发生、发展和转移密切相关。目前发现环氧化酶有两种亚型：     

胃肠肿瘤中信号转导蛋白的表达及其与环氧化酶-2的关系

流行病学资料显示 :在胃肠道肿瘤组织中还氧化酶 - 2 (COX - 2 )呈高表达状态 ,长期服用COX -2抑制剂可降低消化道肿瘤的发病危险性 ,具有一定的化学预防作用。近期研究表明 ,使用COX - 2抑制剂可能通过细胞信号转导通路来诱导肿瘤细胞凋亡和抑制肿瘤细胞生长、增殖 ,这为临床肿瘤治疗又提供了一新的抗癌思路。现就在胃肠肿瘤组织中COX - 2的表达 ,细胞信号转导和肿瘤干预治疗的最新进展作一综述。1　细胞信号转导通路及其在胃肠道肿瘤中的表达1.1　MAPKs信号转导通路丝裂原活化蛋白激酶 (mitigen -activatedpro teinkinases ,MAPKs…     

止痛剂可能是抗癌药的新来源

来自美国俄亥俄州哥伦比亚大学的Ching-Shih Chen博士及其同事在2002年11月的《国家肿瘤协会会刊》上发表文章称,环氧化酶(COX)-2抑制剂将可能被研制成抗癌药。 COX-2抑制剂是一种非甾体类抗炎药(NSAIDs)。传统的NSAIDs同时阻滞COX-2和COX-1。COX-1可以保护胃黏膜,阻滞它会引起胃的刺激。COX-2抑制剂仅仅阻滞COX-2,不影响COX-1的活性。     

COX2与非小细胞肺癌相关性的研究进展

环氧化酶（COX）是催化花生四烯酸转化为前列腺素和血栓烷素的限速酶,主要包括COX1和COX2两个亚型,两者虽结构相似,但在组织中的分布和功能却不尽相同。选择性抑制COX2在肿瘤组织中的表达有可能成为预防和治疗非小细胞肺癌（NSCLC）的新靶点。本文将近年来关于COX2在肺癌中的表达与肺癌的发生、转移和预后的关系及COX2抑制剂在NSCLC治疗方面的应用等研究进行综述。     

阿司匹林等环氧化酶抑制剂对食管癌发病风险影响的系统评价与Meta分析

目的系统评价阿司匹林等环氧化酶抑制剂(COX抑制剂)对食管癌发病风险的影响,以阐明两者间的关系。方法通过检索PubMed、EMBASE、Cochrane library、CNKI数据库,搜索关于使用阿司匹林/NSAIDs与食管癌发病风险影响的临床研究,使用Stata24.0软件进行Meta分析。结果使用COX抑制剂可降低人群患食管癌/食管高度异型增生风险[相对风险RR=0.64,95%CI(0.53～0.77),P=0.512],阿司匹林同样能够降低人群患食管癌/食管高度异型增生的风险[RR=0.63,95%CI(0.43～0.94),P=0.642],非阿司匹林环氧化酶抑制剂也有效果[RR=0.50,95%CI(0.32～0.78),P=0.492],这种化学性预防食管癌作用可能与用药时间相关。结论使用阿司匹林/COX抑制剂可以有效降低食管癌的发生率,但目前报道的相关文献仍然较少,需要更多高质量的研究来佐证。     

COX-2和iNOS在宫颈癌的表达及其预后价值

目的 :研究COX 2和iNOS在宫颈癌发生发展中的作用及其预后价值。方法 :采用免疫组化SP法检测6 4例宫颈癌组织及 31例CIN和 30例正常宫颈组织中COX 2和iNOS的表达水平。结果 :①宫颈癌组织COX 2和i NOS阳性表达率分别为 4 8.4 4 %和 85 .94 % ,明显高于正常宫颈组织 ;②宫颈癌组织COX 2和iNOS的表达水平与临床分期、组织学分型及分化程度无关 (P >0 .0 5 ) ,与高危因素 (淋巴结转移、肿瘤大小、宫旁浸润或脉管浸润 )有关 ;③宫颈癌组织COX 2和iNOS的表达之间未发现相关性 (P >0 .0 5 ) ;④宫颈癌组织COX 2阳性表达与无瘤生存时间缩短和总生存率降低有关。多因素分析表明 ,COX 2阳性表达是宫颈癌患者复发的一个显著预后因素。结论 :宫颈癌组织中COX 2和iNOS表达水平明显上调与宫颈癌的发生发展有关 ;宫颈癌患者预后不良与COX 2表达有关 ,而与iNOS表达无关 ,免疫组化检测COX 2表达可用作预测宫颈癌患者预后的一个分子标志物     

Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer

Context  Randomized trials of short-term aspirin use for prevention of recurrent colorectal adenoma have provided compelling evidence of a causal relationship between aspirin and colorectal neoplasia. However, data on long-term risk of colorectal cancer according to dose, timing, or duration of therapy with aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) remain limited. Objective  To examine the influence of aspirin and NSAIDs in prevention of colorectal cancer. Design, Setting, and Participants  Prospective cohort study of 82 911 women enrolled in the Nurses’ Health Study providing data on medication use biennially since 1980 and followed up through June 1, 2000. Main Outcome Measure  Incident colorectal cancer. Results  Over a 20-year period, we documented 962 cases of colorectal cancer. Among women who regularly used aspirin (2 standard [325-mg] tablets per week), the multivariate relative risk (RR) for colorectal cancer was 0.77 (95% confidence interval [CI], 0.67-0.88) compared with nonregular users. However, significant risk reduction was not observed until more than 10 years of use (P.001 for trend). The benefit appeared related to dose: compared with women who reported no use, the multivariate RRs for cancer were 1.10 (95% CI, 0.92-1.31) for women who used 0.5 to 1.5 standard aspirin tablets per week, 0.89 (95% CI, 0.73-1.10) for 2 to 5 aspirin per week, 0.78 (95% CI, 0.62-0.97) for 6 to 14 aspirin per week, and 0.68 (95% CI, 0.49-0.95) for more than 14 aspirin per week (P<.001 for trend). Notably, women who used more than 14 aspirin per week for longer than 10 years in the past had a multivariate RR for cancer of 0.47 (95% CI, 0.31-0.71). A similar dose-response relationship was found for nonaspirin NSAIDs (P = .007 for trend). The incidence of reported major gastrointestinal bleeding events per 1000 person-years also appeared to be dose-related: 0.77 among women who denied any aspirin use; 1.07 for 0.5 to 1.5 standard aspirin tablets per week; 1.07 for 2 to 5 aspirin per week; 1.40 for 6 to 14 aspirin per week; and 1.57 for more than 14 aspirin per week. Conclusions  Regular, long-term aspirin use reduces risk of colorectal cancer. Nonaspirin NSAIDs appear to have a similar effect. However, a significant benefit of aspirin is not apparent until more than a decade of use, with maximal risk reduction at doses greater than 14 tablets per week. These results suggest that optimal chemoprevention for colorectal cancer requires long-term use of aspirin doses substantially higher than those recommended for prevention of cardiovascular disease, but the dose-related risk of gastrointestinal bleeding must also be considered.      

Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk

Context  Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with a decrease in the risk of several cancers, including breast cancer. NSAIDs inhibit cyclooxygenase activity and thereby reduce prostaglandin synthesis; prostaglandins stimulate aromatase gene expression and thereby stimulate estrogen biosynthesis. Given the importance of estrogen in the pathogenesis of breast cancer, the ability of aspirin and other NSAIDs to protect against breast cancer could vary according to hormone receptor status. Objectives  To determine the association between the frequency and duration of use of aspirin and other NSAIDs and breast cancer risk and to investigate whether any observed association is more pronounced for women with hormone receptor–positive breast cancers. Design, Setting, and Patients  Population-based case-control study of women with breast cancer, including in-person interviews conducted on Long Island, NY, during 1996-1997 (1442 cases and 1420 controls). Main Outcome Measure  Incident invasive and in situ breast cancer by aspirin and NSAID use and hormone receptor status. Results  Ever use of aspirin or other NSAIDs at least once per week for 6 months or longer was reported in 301 cases (20.9%) and 345 controls (24.3%) (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.66-0.97 for ever vs nonusers). The inverse association was most pronounced among frequent users (=" BORDER="0">7 tablets per week) (OR, 0.72; 95% CI, 0.58-0.90). The results for ibuprofen, which was used by fewer women on a regular basis, were generally weaker (OR, 0.78; 95% CI, 0.55-1.10 for <3 times per week vs OR, 0.92; 95% CI, 0.70-1.22 for =" BORDER="0">3 times per week). Use of acetaminophen, an analgesic that does not inhibit prostaglandin synthesis, was not associated with a reduction in the incidence of breast cancer. The reduction in risk with aspirin use was seen among those with hormone receptor–positive tumors (OR, 0.74; 95% CI, 0.60-0.93) but not for women with hormone receptor–negative tumors (OR, 0.97; 95% CI, 0.67-1.40). Conclusion  These data add to the growing evidence that supports the regular use of aspirin and other NSAIDs (which may operate through inhibition of estrogen biosynthesis) as effective chemopreventive agents for breast cancer.      

河南食管癌高发区食管癌组织中COX-2的表达

目的：探讨河南食管癌高发区食管癌组织中COX－2表达变化与食管癌细胞分化程度及淋巴结转移的关系。方法：免疫组化ABC方法检测31例食管鳞癌组织中COX－2的表达，以活检正常食管粘膜10例为对照。结果：COX－2免疫阳性反应主要定位于食管癌细胞的细胞质，正常对照组无COX－2表达。31例食管癌组织中有16例（51．6％）表达COX－2；食管癌组织分化的恶性程度与COX－2免疫反应的强度呈负相关（r=-0.564;P=0.001);伴淋巴结转移者61．9％COX－2阳性（13／21），但统计分析未发现COX－2的免疫反应程度与有无淋巴结转移间存在相关性（K－S Z＝0．830；P＝0．496）。结论：COX－2过度表达可能与食管癌细胞分化程度有关，可能成为食管癌防治，特别是高分化食管癌治疗的新靶点。     

幽门螺杆菌cagA菌株感染与胃癌组织中环氧化酶-Ⅱ表达的相关性研究

目的：探讨幽门螺杆菌cagA(Hp-cagA)菌株感染与胃癌组织中环氧化酶－Ⅱ（COX-2）表达之间的关系,为胃癌的早期预防提供有价值的实验和理论依据。方法：采用流式细胞术定量检测及分析31例胃癌组织及相应的癌旁正常胃组织中COX－2的表达水平,并通过PCR技术对胃癌组织中cagA基因进行扩增检测。结果：31例胃癌组织中,有26例COX－2过表达,相应的26例癌旁正常组织基本上无表达或弱表达。18例cagA阳性的胃癌组织中COX－2的表达水平明显高于13例cagA阴性的胃癌组织。结论：COX－2在胃癌组织中过度表达,cagA菌株感染可上调胃癌组织中COX-2绵表达水平。可能存在cagA菌株感染之外的其他因素或机制调节COX－2的表达。因此,在根治Hp感染的同时,应用COX－2特异性抑制剂可能是一种有效预防胃癌发生、发展的新路。     

阿司匹林抵抗与环氧化酶基因多态性研究进展

阿司匹林目前被认为是预防心脑血管疾病再发的最有效的血小板聚集抑制物,其通过抑制环氧化酶(COX)活性发挥作用。但随访发现一些长期规律口服常规剂量阿司匹林的患者仍发生血栓栓塞事件,即存在"阿司匹林抵抗"现象。COX有三种同工酶,其中COX-1、COX-2存在广泛的基因多态性,其基因突变影响COX的转录及酶活性,从而干扰阿司匹林的抗血小板作用。     

膜结合型透明质酸酶PH-20 mRNA在消化道肿瘤表达的意义

目的研究膜结合型透明质酸酶(PH-20)mRNA表达与消化道肿瘤侵袭能力及淋巴结转移的关系,探讨其预测肿瘤侵袭危险度的意义。方法采用逆转录聚合酶链反应(RT-PCR)检测59例消化道肿瘤患者的原发癌、癌旁组织、淋巴结转移癌(其中13例)及4例消化道良性病变和各种细胞系(SGC-7901、BGC823、LS-174-T、HCT8、95-D、A549、HFL、HEPG2、L-02)中PH-20mRNA的表达水平。结果PH-20mRNA在上述组织中均有表达,消化道原发癌和淋巴结转移癌均明显高于癌旁组织(P<0.05)。消化道肿瘤PH-20mRNA表达与肿瘤浸润程度有关,浸润性肿瘤的PH-20mRNA表达量高于浅表性肿瘤(P<0.01)。结论PH-20mRNA表达改变可能与消化道肿瘤的发展有关,高表达PH-20mRNA的肿瘤细胞具有高侵袭潜能。     

The effect of folic acid on the development of stomach and other gast rointestinal cancers

Objective To evaluate the roles of folic acid and β-carotene in the chemoprevention of gastric and other gastrointestinal(GI)cancers.Methods In a randomized,double-blind,placebo-controlled trial,a total of 216 patients with atrophic gastritis were randomly assigned to one of the four groups:①folate(FA),20 mg per day plus vitamin B12 1 mg,intramuscularty,per month for one year,then 20 mg two times a week plus 1 mg per three months for the next year);②naural β-carotene(N-βC,30mg per day for first year,then 30mg two times a week for the next);③synthetic β-carotene(S-βC,administered as in N-βC);and ④placebo.Follow-ups continued from 1994 to 2001.Results A total of 7new cases of gastrointestinal cancers were diagnosed with 3 stomach,1 colon and 1 esophageal cancers occurring in the placebo group;1 stomach cancer in both of the N-βC and S-βC groups,and no cancer occurring if FA group.In terms of GI cancers,there was a significant reduction in the FA group,compared with the placebo group(P=0.04).A similar trend was observed in both N-βC and S-βC groups(P=0.07-0.08),Taken together,the three intervention groups displayed a highly significant decrease in occurrence(P=0.04,vs placebo),and a lower risk for GI cancers(OR=0.12;95?confidence interval,0.03-0.51).For development of gastric cancer,any one of the three active-treated groups did not reach statistically significant reduction.The FA group showed obvious improvement of the gastric mucosal lesions with more patients displaying lesions reversed or stable atrophy and inflammation(P=0.04).reversed intestinal metaplasia(P=0.06)at the end of follow-up,and reversed displasia(P=0.017)at 12 months.Two cases of false jaundice were found in β-carotene groups with no influence on administration,and no side-effects were reported in FA group. Conclusions This trial revealed the interventional effect of folic acid on the development of GI cancers,a similar effect of β-carotene was also detected.Also,folic acid may be of use to treat atrophic gastritis by preventing or reversing the precancerous lesions.