COX-2及其选择性抑制剂在胃癌中的研究进展

环氧合酶-2(COX-2)是花生四烯酸合成前列腺素的关键限速酶.近年来大量研究表明,COX-2的高表达在胃癌肿瘤细胞进展中发挥着重要作用,其选择性抑制剂能够降低胃癌的发生率.     

COX-1和COX-2在结直肠腺瘤中的表达

目的观察COX-1和COX-2在结直肠腺瘤中的表达情况。方法16例经病理证实的散发性结直肠腺瘤活组织检查标本，15例肠镜检查无明显病变的IBS患者肠黏膜活组织检查标本。免疫组化染色观察COX-1和COX-2表达水平的变化。结果COX-2在结直肠腺瘤组织中的表达异常增高（P〈0．05），而COX-1在正常组织和腺瘤中的表达水平没有明显的变化。结论在结直肠腺瘤组织中，COX-2表达明显升高，提示COX-2参与结直肠腺瘤的发生和发展。     

5-LOX mRNA和COX-2 mRNA在结直肠癌中的表达及二者的相互关系

目的 研究5脂氧合酶(5-LOX)和环氧合酶2(COX-2)在结直肠癌中的表达及二者的相互关系.方法 用RT-PCR检测39例结直肠癌标本中5-LOX mRNA和COX-2 mRNA的表达.结果 5-LOX mRNA和COX-2 mRNA在结直肠癌组织中的表达率分别为84.6%(33/39)及76.9%(30/39),均与结直肠癌临床分期、肿瘤大小、肿瘤分化程度有关.但两者无相关性(P＞0.05).结论 5-LOX mRNA和COX-2 mRNA在结直肠癌组织中表达增高,提示了在研究结直肠癌治疗和预防时可采取对代谢途径抑制这一新方向.     

环氧合酶2及其抑制剂与动脉粥样硬化的研究进展

动脉粥样硬化(AS)所致的心、脑、肾血管疾病是严重危害人类健康的重大疾病.目前认为AS是一种炎症性疾病[1].其病理变化具有炎症的基本特征,各种炎症细胞和炎性介质参与了其发病.     

环氧合酶-2与幽门螺杆菌感染

环氧合酶-2(COX-2)与胃癌关系研究的初步成果引起了国内外研究者的广泛关注，业已明确幽门螺杆菌(Hp)感染是胃癌发生的重要病因，Hp感染可诱导胃粘膜COX-2表达上调，而COX-2表达与胃癌形成密切相关，Hp根除治疗对COX-2表达的长期影响值得关注。Hp感染导致胃癌的发病机制可能与COX-2活性升高有关。     

环氧合酶-2抑制剂在抗结肠癌中的研究进展

环氧合酶(COX)是花生四烯酸合成前列腺素及血栓素的关键酶,其中COX-2为诱导酶,在机体炎性反应、肿瘤细胞刺激时可高表达,从而促进肿瘤细胞增殖,加速恶性肿瘤患者病情进展。故调控COX-2表达,已成为防治恶性肿瘤的新途径。近年来,COX-2抑制剂逐渐应用于抗结肠癌治疗中,该文就COX-2抑制剂在抗结肠癌中的研究进展作一综述。     

环氧合酶-2及其抑制剂与肝癌关系的研究进展

环氧合酶-2与肿瘤发生和发展关系的研究日益增多,它与肝癌的关系同样受到关注.本文就环氧合酶-2的结构、功能、与肿瘤(尤其是肝癌)发生的关系及其抑制剂干预的相关研究进展予以综述.     

环氧合酶-2抑制剂吡罗昔康对结肠癌细胞生长的影响

目的观察非甾体类抗炎药、环氧合酶(COX)-2抑制剂吡罗昔康(Piroxicam)对结肠癌细胞的影响，并结合COX-2蛋白表达和细胞凋亡情况探讨结肠癌的预防。方法细胞株选用SW1116结肠腺癌细胞；细胞增殖实验时，用MTT法测定细胞增殖活性；用免疫组化及Western Blot方法检测细胞内COX-2蛋白表达；用DNA云梯电泳法检测细胞凋亡。结果吡罗昔康能够抑制结肠腺癌细胞的增殖，其效应与浓度呈正相关；浓度≥1．0mmol／L时呈现细胞毒作用。吡罗昔康作用12h即可显著抑制COX-2蛋白的表达；作用24h后，蛋白水平恢复程度与浓度成负相关。吡罗昔康浓度≥0．1mmol／L时可以诱导SW1116细胞的凋亡。结论吡罗昔康抑制结肠腺癌细胞的增殖与抑制COX-2过度表达和促进细胞凋亡有关，由于吡罗昔康的效应呈现浓度和时间依赖性，在进行预防或治疗结肠癌的临床研究时，要考虑其有效剂量和用药间隔。     

重视环氧合酶—2与消化系肿瘤关系的研究

环氧合酶（cyclooxygenas,COX）是催化花生四烯酸转化为前列腺素（PGs）的关键酶,有COX－1和COX－2两种异构酶。COX－1存在于大多数细胞和组织中,产生具有重要生理作用的PGs,在胃肠道具有细胞保护作用;相反,COX-2在许多组织中几乎不能测得,在组织损伤、炎症或细胞恶性转化时表达增强。COX－1和COX-2的生物活性均能被阿司匹林和其他非好甾体类抗炎药（NSAIDS）所抑制,而选择性COX-2抑制剂N4主要抑制COX－2。410年来大量研究表明,COX-2的过度表达与肿瘤,特别是消化系肿瘤的发生、发展密切相关,现就这方面的研究进…     

COX-2与卵巢癌的相关性研究进展

环氧化酶（COX）是前列腺素H2合成的限速酶,在花生四稀酸转变成前列腺素（PGS）的过程中发挥着重要作用,包括COX-1和COX-2两种同工酶。研究发现。COX-2与绝大多数恶性肿瘤的发生发展有关。现将其与卵巢癌的相关性研究进展情况综述如下。     

环氧化酶2在大肠癌中的表达及其与大肠癌生物学特性的关系

[目的]通过观察环氧化酶2（Cyclooxygenase-2,COX-2）在大肠腺瘤、大肠癌中的表达及其与大肠癌生物学特性的关系,初步探讨其在大肠癌发生、发展过程中的作用机制。[方法]应用免疫组织化学染色法对78例大肠癌组织、21例大肠腺瘤组织和13例正常大肠黏膜组织进行免疫组化染色;应用它检验分析COX-2的表达情况及其与大肠癌临床病理特征的关系。[结果]大肠癌组织中COX-2阳性表达率为78．21％,明显高于大肠腺瘤的52．38％和正常大肠黏膜组织的7．69％（P〈0．05）;COX-2表达与大肠癌的Duke＇s分期、分化程度、淋巴结转移有相关性（P〈0．05）,而与大肠癌患者的性别、组织学类型无关（P〉0．05）。[结论]COX-2在大肠癌组织中表达率明显高于大肠腺瘤,而正常大肠黏膜中表达率极低或不表达;COX-2表达与大肠癌生物学特性有明显相关性。     

Targeting cyclooxygenase-2 with sodium butyrate and NSAIDs on colorectal adenoma／carcinoma cells

AIM: The protective effects of sodium butyrate and NSAIDs (especially the highly selective COX-2 inhibitors) have attracted considerable interest recently. In this study, primary adenoma cells and HT-29 were used to investigate whether the above drugs would be effective for reducing proliferation and inducing apoptosis. Additionally, it was investigated whether NSAIDs would strengthen the effects of sodium butyrate and its possible mechanisms. METHODS: In vitro primary cell culture of colorectal adenomas and HT-29 were used for this investigation. PGE2 isolated from HT-29 cell culture supernatants was investigated by ELISA. MTT was employed to detect the anti-proliferative effects on both adenoma and HT-29 culture cells. FCM was used for apoptosis rate and cell cycle analysis. The morphology of apoptotic cells was investigated by means of electromicroscopy. RESULTS: Sodium butyrate could stimulate the secretion of PGE2, while NSAIDs inhibited it to below 30 pg/10(6) cells. Both butyrate and NSAIDs could inhibit cell proliferation and induce apoptosis. The effects were time- and dose-dependent (P<0.05). Aspirin and NS-398 could enhance the effects of sodium butyrate. The effects were stronger while sodium butyrate was used in combination with NS-398 than it was used in combination with aspirin. CONCLUSION: Butyrate and NSAIDs could inhibit cell proliferation and induce apoptosis respectively. NSAIDs could enhance the effects of sodium butyrate by down-regulating COX-2 expression. Selective COX-2 inhibitor is better than traditional NSAIDs.     

Progastrin and cyclooxygenase-2 in colorectal cancer

Colorectal cancers (CRCs) are one of the most common forms of cancer in Poland and one of the leading causes of death. The tumors have been attributed to genetic, dietary, and other environmental factors, but recently growth factors such as gastrin have also been implicated in the carcinogenesis. The relationship between plasma amidated and nonamidated gastrin in CRCs is controversial. This study was designed (1) to determine the plasma levels of progastrin and amidated gastrin in 50 CRC patients before and 3–6 months after removal of the tumor, (2) to determine the tumor concentrations of these gastrin peptides and the level of expression for gastrin mRNA and gastrin/CCK_B receptor mRNA, (3) to examine the expression of cyclooxygenase COX-1 and COX-2 mRNA in CRC tissue, and (4) to compare the prevalence of Hp and its cytotoxic protein, CagA, and cytokines (TNF, IL-1, and IL-8) in CRCs, before and after removal of tumor. It was found that the CRC, its resection margin, and the plasma contained severalfold higher levels of progastrin than of amidated gastrins and that the removal of the CRC tumor resulted in a marked reduction in plasma progastrin level without a significant alteration in plasma levels of amidated gastrins. Both gastrin and CCK_B-R mRNA were detected in the cancer tissue and resection margin by RT-PCR, and similarly, COX-1 and COX-2 mRNA were expressed in these tissues of most CRCs. The seroprevalence of Hp, especially that expressing CagA, and levels of IL-1, but not other cytokines, were significantly higher in CRC patients than in 100 age-, gender-, and profession-matched controls and did not change significantly about 3–6 months after tumor resection. We conclude that (1) the CRC and its margin contain large amounts of progastrin and show gene expression of gastrin, CCK_B-R, and COX-2; (2) removal of the CRC markedly reduces the plasma concentrations of progastrin; (3) the Hp infection rate is higher in CRC, and this may contribute to colorectal cancerogenesis via enhancement of progastrin and gastrin release; and (4) plasma progastrin concentrations might serve as a biomarker of CRC.     

Expression of cyclooxygenase-2 protein in colorectal carcinomas

Summary Background. Overexpression of cyclooxygenase-2 (COX-2) has been demonstrated in various human cancers, including colorectal cancer. Thus, overexpression of COX-2 may be involved in the growth and progression of cancer, and this may have prognostic significance. Aim. The aim of our study is to evaluate the expression of COX-2 in colorectal cancer tissue, and to examine the relationship of its expression to various clinicopathological parameters and patient survival. Methods. Formalin-fixed, paraffin-embedded tissue blocks were obtained from 60 patients who underwent surgery for colorectal carcinoma in 1995 at the Chonnam National University Hospital in Gwangju, Korea. We have used an immunohistochemical technique to localize COX-2 in colorectal carcinoma tissues. Results. Immunohistochemical staining of the colorectal cancer specimens demonstrated that COX-2 expression was localized to the carcinoma cells and was not detectable in the stromal compartment of the cancers. The COX-2 immunostaining pattern was predominantly homogenous, and perinuclear cytoplasmic within the tumors. Normal colonic epithelium adjacent to the tumor showed no staining for COX-2. The COX-2 protein was detected in 70% (42/60) of colorectal carcinoma tissues. However, no significant correlation was found between COX-2 expression and various clinicopathological parameters, including histologic grade, tumor size, depth of invasion, lymph node metastasis, distant metastasis, or stage. Furthermore, COX-2 expression did not correlate with patient survival (p=0.401). Conclusion. These results suggest that COX-2 expression may play an important role in the evolution of colon carcinogenesis. However, further studies are needed to determine the prognostic relevance of COX-2.     

COX-2在食管癌中的表达及其意义

目的通过研究COX-2和PGE2在食管癌中的表达,探讨COX-2与食管癌的关系.方法分别采用RT-PCR、免疫组织化学和放射免疫分析等方法研究食管腺癌和食管鳞癌病人内窥镜活检组织中COX-2及其mRNA的表达率以及PGE2在组织中的含量.结果RT-PCR法研究显示,食管腺癌组(88.24%)、食管鳞癌组(72.73%)中COX-2 mRNA表达率与正常组织(25.00%)相比有显著差异(P＜0.01);免疫组织化学研究显示,食管腺癌和食管鳞癌的癌细胞胞浆中COX-2蛋白呈阳性表达,食管腺癌组(76.47%)、食管鳞癌组(72.73%)中COX-2蛋白表达率与正常组织(20.00%)比有显著差异(P＜0.01).放射免疫分析法研究显示,食管腺癌组(559.22±37.77)、食管鳞癌组(563.52±41.12)中PGE2的含量(pg/mg)与对照组(357.10±37.58)相比有显著差异(P＜0.05),前两组中PGE2的含量之间无显著差异(P＞0.05).结论食管腺癌和食管鳞癌中COX-2蛋白及其mRNA均呈高表达,PGE2的含量增高.     

大肠癌和大肠腺瘤COX-2和BFGF表达的意义

目的:研究COX-2和BFGF在大肠癌及大肠腺瘤组织中的表达及意义．方法:采用免疫组化SP方法检测了手术切除的大肠癌49例,腺瘤性息肉25例,正常大肠黏膜组织20例中的COX-2和BFGF表达．结果:COX-2和BFGF在大肠癌中的表达阳性率分别为59．2％和69．3％,在腺瘤性息肉的表达率为52．0％和56．0％,COX-2和BFGF在大肠癌组织与腺瘤性息肉中表达无显著性差异(P>0．05):正常肠黏膜中未检出COX-2和BFGF．COX-2和BFGF在大肠癌中表达与性别,年龄,肿瘤大小,肿瘤位置,分化程度无关(P>0．05)．但与肿瘤Dukes分期有关,C,D期高于A,B期(81．5％vs 54．5％,P<0．05),淋巴结转移之间具有显著性差,有异淋巴结转移高于无淋巴结转移(81．5％vs 54．5％,P<0．05)．肠癌组织中COX-2、BFGF表达二者间有相关性(r= 0．349,P<0．05)．结论:COX-2、BFGF在大肠癌组织及大肠腺瘤中的表达水平增高,在大肠腺瘤恶变及大肠癌的发生发展过程中起协同作用,共同促进肿瘤的发生．     

Role of cyclooxygenase-2 in the angiogenesis of colorectal cancer

BACKGROUND: Cyclooxygenase (COX) is the rate-limiting enzyme in the synthesis of prostaglandins. It exists in two isoforms: COX-1 which is constitutively expressed and COX-2 which is an inducible form activated by a variety of cytokines during inflammation. DISCUSSION: Interest in this enzyme arose in the early 1990s when, following epidemiological studies, aspirin (which is a COX inhibitor) was found to reduce the risk of colorectal cancer. Since then various studies to decipher the mechanisms by which COX reduces the development of colorectal cancer have been undertaken. One of the mechanisms being studied is its role in the angiogenesis of colorectal cancer. Angiogenesis of its own has been well established as a key factor in the development of tumours. Agents that specifically inhibit COX-2 are now in clinical development and have been licensed to be used in patients with familial adenomatosis polyposis. CONCLUSION: What needs to be determined is whether the antiangiogenic effects of COX-2 inhibitors can be used in the prevention and/or treatment of colorectal cancer and its metastases.     

Genetic polymorphisms in the cyclooxygenase-1 and cyclooxygenase-2 genes and risk of colorectal adenoma

Purpose  Cyclooxygenase (COX) enzymes, COX1 and COX2, are key in converting arachidonic acid (AA) into prostaglandins that have been associated with colorectal carcinogenesis. The aim of our study was to investigate associations of polymorphisms in COX genes, alone and in interaction with exposures known to be related to inflammation and AA metabolism, with risk of colorectal adenomas. Materials and methods  In a community-, colonoscopy-based case–control study with 162 incident, sporadic colorectal adenoma cases and 211 controls, we investigated associations of two promoter polymorphisms (−842 A  > G in COX1 and −765 G > C in COX2) and two polymorphisms in the 3′-UTR of COX2 (8473 T > C and 9850 A > G) with risk of adenomas. Multiple logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) of colorectal adenoma after adjusting for potential confounders. Results  Overall, there was no evidence for an association between any of the four polymorphisms and colorectal adenomas. However, we found a statistically significant interaction between the COX2 8473 T > C polymorphism and nonsteroidal anti-inflammatory drug (NSAIDs) use (P _interaction = 0.03): The greatest reduced risk was observed for individuals with the 8473 C variant allele who also regularly used NSAIDs (OR = 0.35, 95% CI 0.16–0.75). Conclusion  These results suggest that the C allele of COX2 8473 T > C polymorphism may interact with NSAIDs to reduce risk for colorectal adenoma.