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。     

环氧化酶-2与胃癌的研究进展

环氧化酶（COX）-2是花生四烯酸合成前列腺素的限速酶,在胃癌高表达,其表达与炎性因子、肿瘤促进子及幽门螺杆菌感染等多种因素有关。COX-2的高表达通过抑制细胞凋亡、促进新生血管的形成及帮助肿瘤细胞逃逸机体免疫监视等多种作用促进肿瘤的发生及发展。COX-2可以降低肿瘤细胞间的黏附性、促进基底膜的降解及新生淋巴管的形成,促进肿瘤的浸润和转移。COX-2有望成为胃癌治疗的新靶点。     

幽门螺杆菌感染与胃粘膜环氧化酶-2表达的关系

环氧化酶(COX)是合成前列腺素的限速酶。该酶有两种异构体，即COX-1和COX-2。最近研究显示，COX-2表达与胃肠道肿瘤的发生有关。幽门螺杆菌(Hp)感染是慢性活动性胃炎的主要病因，也是胃癌发生的危险因素。2000～2001年，我们对97例胃病患者进行了Hp及胃粘膜COX-2检测，旨在探讨Hp感染与胃粘膜COX-2表达的关系。     

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…     

幽门螺杆菌感染诱导胃粘膜环氧化酶-2表达

1983年发现幽门螺杆菌(Hp)以来,有关Hp在慢性活动性胃炎、慢性萎缩性胃炎和消化性溃疡发病中的作用已引起国内外学的高度重视,并且认为,Hp是胃腺癌发生的一种Ⅰ类(肯定)致癌物。流行病学资料提示,Hp感染人群胃癌发生危险性显高于对照人群。动物实验证实,Hp慢性感染易引起胃粘膜组织恶性转化,但其致癌机制尚不清楚。     

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。     

围术期口服环氧化酶-2抑制剂对术后镇痛效果的影响

目的通过围术期口服选择性环氧化酶（COX）-2抑制剂,观察妇科术后患者的镇痛效果与血清中血栓素（TX）B2、前列腺素（PG）E2与脑脊液中PG水平的变化。方法60例择期行妇科手术者,随机分为3组,每组20例。A组：麻醉前1h至术后48h口服选择性COX-2抑制剂尼美舒利100mg,1次／12h;B组：麻醉前1h至术后48h内口服非选择性COX抑制剂布洛芬400mg,1次／6h;C组：不服用任何药物。分别于麻醉前,术后24、48h测定脑脊液中6-酮PGF1α和血清中TXB2、PGE2水平。3组术后均采用静脉自控止痛泵（PCA）注射吗啡进行术后止痛,记录术后2、6、12、24、48h的视觉模拟评分（VAS）和术后48h累计吗啡需要量。结果术后48hA组脑脊液中6-酮PGF1α水平与术前比较无差异,但明显低于B、C组（P〈0．05）;术后6、12、24h,A组VAS评分和术后48h累计吗啡总需要量明显低于B,C组（P〈0．05）。结论围术期口服选择性COX-2抑制剂比其他非甾体类抗炎药（NSAIDs）的镇痛效果好。     

质子泵抑制剂联合氯吡格雷在心血管疾病治疗中的研究进展

抗血小板药物可有效减少血栓事件的发生,但增加胃肠道出血风险,通常加用质子泵抑制剂(PPI)来避免抗血小板药物所导致的黏膜损害。PPI具有与氯吡格雷相同的肝脏的代谢途径,可能降低氯吡格雷的抗血小板疗效并导致发生不良心血管事件的危险增加。氯吡格雷与PPI联合应用是否影响抗血小板药物治疗效果,目前对这一现象尚无定论,该文就氯吡格雷与PPI相互作用的机制和临床研究进展作一综述。     

Association of proton pump inhibitors with the occurrence of gut-derived bacteraemia in patients with haematological malignancy after chemotherapy

Background: Gut-derived bacteraemia is a major complication in patients with haematological malignancy after chemotherapy.

Objective: Our study aimed to investigate the role of proton pump inhibitors (PPIs) in the occurrence of gut-derived bacteraemia.

Methods: We compared data from 92 hospitalized haematological malignancy patients after chemotherapy with gut-derived bacteraemia, collected from January 2009 to July 2015, with those of 92 contemporaneous, hospitalized haematological malignancy patients without bacteraemia. We evaluated PPIs use and analysed the effects of covariates.

Results: Patients with gut-derived bacteraemia had a significantly higher incidence of PPIs use (69.6%) than that of controls (47.8%). Of the patients with gut-derived bacteraemia, only 44.6% had a documented indication for PPIs therapy. The antibacterial prophylaxis rate was 38.0% in the bacteraemia group and 58.7% in the non-antibacterial group. Based on multivariable logistic regression analysis, only PPIs use (P?=?0.00, odds ratio (OR)?=?0.546) was found to be associated with the risk of bacteraemia whereas antibacterial prophylaxis (P?=?0.00, OR?=?0.652) was protective. There were no significant differences in demographics, malignancy status, length of neutropenia, complications, or steroid use between the gut-derived bacteraemia and control group.

Conclusions: This study suggests a potential association between PPIs use and development of gut-derived bacteraemia in haematological malignancy patients after chemotherapy.     

In vivo effect of proton-pump inhibitors on gastric plasmin-dependent fibrinolysis: A study in a porcine model

Introduction

Alkalization of gastric fluids could inhibit plasmin-mediated and/or pepsin-mediated fibrinolysis. We evaluated the gastric antifibrinolytic effect of proton pump inhibitors in a live porcine model.

Material and methods

Six pigs were randomly assigned to treatment with proton pump inhibitors vs no treatment. After endoscopic mucosal resection, 8 μm sections were incubated on fibrin films. Fibrinolytic activity was assessed through focal lysis time. One-hundred-and-forty-two mucosal sections and 129 submucosal sections were analysed. Twenty-four additional sections were analysed on plates containing tranexamic acid to explore pepsin-mediated fibrinolysis.

Results

Focal lysis times in treated vs control groups were 21.0 min vs 21.2 min (p = 0.39) in the mucosa, and 22.2 min vs 20.2 min (p = 0.56) in the submucosa. No lysis could be seen on the plasmin-inhibited fibrin plates.

Conclusion

Only plasmin-mediated fibrinolysis was observed. Proton pump inhibitors had no significant plasmin-dependant antifibrinolytic effect. They may enhance haemostasis through different pathways.     

Effects of NC-1300, a gastric proton pump inhibitor,on healing of acetic acid-induced gastric ulcers in rats

Effects of NC-1300 (a gastric proton pump inhibitor) on healing of experimental chronic gastric ulcers induced in rats were studied. Gastric ulcers were induced by the submucosal injection of 20% acetic acid (0.03 ml) into the antral-oxyntic border of the anterior wall of male Donryu rats (260–280 g). The healing of acetic acid ulcers was delayed by the daily subcutaneous administration of indomethacin (1 mg/kg) for two or four weeks after ulceration. Aggravation of healed ulcers was evoked by subcutaneous administration of indomethacin (1 mg/kg) once daily for four weeks to rats with four-week-old ulcers. Oral administration of NC-1300 (10, 30, or 100 mg/kg) once daily for two or four weeks after ulceration dose-dependently accelerated both natural and delayed healing of acetic acid ulcers. When the period of administration was extended from two to four weeks, the ED₅₀ values (the dose reducing the ulcerated area by 50%) were decreased from 36.5 to 13.5 mg/ kg in natural healing and from 76.0 to 23.0 mg/kg in delayed healing. Aggravation of four-week-old ulcers by indomethacin was significantly prevented by daily administration of NC-1300 (30 or 100 mg/kg) for four weeks. Acetic acid ulcers that were healed with NC-1300 given for four weeks after ulceration remained healed for four to eight weeks after the cessation of drug administration. A single administration of NC-1300 to normal rats and repeated administration of NC-1300 to rats with acetic acid ulcers for four weeks after ulceration caused the same degree of inhibition of gastric acid secretion. Reduction in the area of ulceration and inhibition of gastric acid secretion by NC-1300 were significantly correlated in the indomethacin-treated animals. We conclude that NC-1300 markedly accelerates the healing of chronic gastric ulcers and prevents aggravation of the healed ulcers, presumably through antisecretory activities.     

The efficacy of proton pump inhibitors in nonulcer dyspepsia: a systematic review and economic analysis

BACKGROUND AND AIMS: The evidence that proton pump inhibitor (PPI) therapy affects symptoms of nonulcer dyspepsia is conflicting. We conducted a systematic review to evaluate whether PPI therapy had any effect in nonulcer dyspepsia and constructed a health economic model to assess the cost-effectiveness of this approach. METHODS: Electronic searches were performed using the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL, and SIGLE until September 2002. Dyspepsia outcomes were dichotomized into cured/improved versus same/worse. Results were incorporated into a Markov model comparing health service costs and benefits of PPI with antacid therapy over 1 year. RESULTS: Eight trials were identified that compared PPI therapy with placebo in 3293 patients. The relative risk of remaining dyspeptic with PPI therapy versus placebo was .86 (95% confidence interval, .78-.95; P = .003, random-effects model) with a number needed to treat of 9 (95% confidence interval, 5-25). There was statistically significant heterogeneity between trials (heterogeneity chi(2) = 30.05; df = 7; P < .001). The PPI strategy would cost an extra US dollar 278/month free from dyspepsia if the drug cost US dollar 90/month. If a generic price of US dollar 19.99 is used, then a PPI strategy costs an extra US dollar 57/month free from dyspepsia. A third-party payer would be 95% certain that PPI therapy would be cost-effective, provided they were willing to pay US dollar 94/month free from dyspepsia. CONCLUSIONS: PPI therapy may be a cost-effective therapy in nonulcer dyspepsia, provided generic prices are used.     

Safer endoscopic gastric mucosal resection: preoperative proton pump inhibitor administration

BACKGROUND AND AIM: Control of bleeding is crucial in improving the safety of endoscopic mucosal resection (EMR), and intragastric acidity has a great impact on hemostasis and blood coagulation. Proton pump inhibitors (PPI) are potent suppressors of gastric acid; however, PPI need to be continuously administered orally for several days, and thus initial effects may be insufficient if PPI is only administered immediately after EMR. The aim of this study was to determine whether preoperative administration of PPI prior to EMR can elevate intragastric acidity, facilitate better control of intraoperative bleeding (complete coagulation and hemostasis), prevent postoperative bleeding, and facilitate healing of artificial ulcers. METHODS: A randomized clinical study was conducted in which EMR was performed with or without 1 week of preoperative PPI administration. RESULTS: Artificial ulcers created by EMR healed more rapidly in patients who received preoperative PPI. CONCLUSIONS: The results of the study suggest that preoperative administration of PPI before EMR is useful for controlling and preventing bleeding, and for facilitating the healing of artificial ulcers.     

Severe systemic adverse reaction to proton pump inhibitors in an infant

Episodes of respiratory distress with chest retraction and wheezing, sometimes associated with facial edema, were noted after administering the proton pump inhibitors omeprazole and esomeprazole in an infant with gastroesophageal reflux. The disturbances relieved dramatically after withdrawing the proton pump inhibitor.     

不同质子泵抑制剂对冠脉支架术后氯吡格雷抗血小板功能的影响

目的:观察埃索美拉唑、雷贝拉唑、雷尼替丁或法莫替丁对急性冠脉综合症（ACS）患者冠脉支架术后应用氯吡格雷抗血小板功能的影响。方法: 150例行经皮冠状动脉介入治疗（PCI）的ACS患者,入院后给予阿司匹林300 mg/d,氯吡格雷300 mg负荷剂量继以75 mg/d维持剂量抗血小板治疗,并随机分为质子泵抑制剂（PPI）A组（A1组:埃索美拉唑40 mg/d,n=30,A2组:雷贝拉唑20 mg/d,n=30）、H2受体拮抗剂(H2RA)B组（B1组:雷尼替丁300 mg/d,n=30,B2组:法莫替丁40 mg/d,n=30）和空白对照C组（C组:n=30）。采用ELISA法检测血浆CD62P、GPⅡb/Ⅲa含量及电阻抗法检测血小板聚集功能。结果: PPI或H2RA治疗前后,A组、B组与C组相比,上述指标的差值组间比较均无明显统计学差异,A1组、A2组、B1组、B2组与C组相比,治疗前后上述指标的差值组间比较均无统计学差异。结论: 埃索美拉唑、雷贝拉唑、雷尼替丁或法莫替丁对氯吡格雷的抗血小板活性无明显的影响。