环氧化酶-2与食管癌的研究进展

环氧化酶-2(COX-2)在恶性肿瘤中的作用日益受到重视,多数食管癌COX-2蛋白高表达,与食管癌发生发展和预后密切相关.COX-2通过诱导肿瘤血管生成、促进细胞增殖、抑制细胞凋亡、增加肿瘤侵袭力、抑制免疫及诱导前致癌物的活性等机制促进食管癌的生长和浸润,选择性COX-2抑制剂的开发和应用有望为食管癌预防和治疗开辟新的途径,成为食管癌分子靶向治疗新的方向.     

环氧化酶-2与食管癌

环氧化酶-2(COX-2)在恶性肿瘤中的作用日趋受到重视,但其确切作用机制尚不清楚.COX-2高表达可通过抑制细胞凋亡、诱导肿瘤血管生成等途径促进食管癌的生长和浸润,选择性COX-2抑制剂的开发和应用有望为食管癌预防和治疗开辟新的途径.     

环氧化酶-2与食管癌

环氧化酶-2（COX-2）在恶性肿瘤中的作用日趋受到重视，但其确切作用机制尚不清楚。COX-2高表达可通过抑制细胞凋亡、诱导肿瘤血管生成等途径促进食管癌的生长和浸润，选择性COX-2抑制剂的开发和应用有望为食管癌预防和治疗开辟新的途径。     

环氧化酶-2抑制剂治疗胰腺癌机制研究进展

环氧化酶-2(COX-2)在胰腺癌发生、浸润和转移中起着重要作用,选择性COX-2抑制剂治疗胰腺癌的作用机制包括减少前列腺素的合成、抑制细胞增殖、诱导细胞凋亡和抑制肿瘤血管生成等.     

环氧化酶-2抑制剂治疗胰腺癌机制研究进展

环氧化酶-2（COX-2）在胰腺癌发生、浸润和转移中起着重要作用，选择性COX-2抑制剂治疗胰腺癌的作用机制包括减少前列腺素的合成、抑制细胞增殖、诱导细胞凋亡和抑制肿瘤血管生成等。     

环氧合酶-2及其抑制剂与子宫内膜癌

环氧合酶-2(COX-2)参与子宫内膜癌的发生、发展,可能影响其预后.COX-2在子宫内膜癌中的表达诱导肿瘤细胞增殖,抑制细胞凋亡,促进肿瘤细胞侵袭和转移.因此,COX-2抑制剂有望成为子宫内膜癌新的防治方法.     

炎症在食管癌发生发展中作用的研究进展

食管癌是消化道常见的恶性肿瘤之一,食管癌根据组织形态学特点主要分为食管鳞状细胞癌和食管腺癌。目前有较多的研究发现,食管癌的发生发展与炎症因素密切相关。环氧化酶-2（COX-2）、前列腺素E2（PGE2）、表皮生长因子受体（EGFR）等均在食管癌中存在过度表达,并与肿瘤的侵袭和转移及预后密切相关。选择性COX-2抑制剂的开发和应用有望为食管癌预防和治疗开辟新的途径。在临床上可能为食管癌分子靶向治疗提供一定的科学依据。     

戊地昔布对人食管癌细胞凋亡及COX-2表达的影响

目的:探讨戊地昔布对人食管癌Eca109细胞系凋亡及环氧化酶-2表达的影响。方法:采用MTT法检测戊地昔布对人食管癌Eca109细胞生长的作用,流式细胞术检测细胞凋亡和细胞周期分布,电子显微镜进一步检测细胞凋亡,RT-PCR及流式细胞术检测COX-2mRNA及蛋白的表达。结果:戊地昔布(25～400μmol/L)依时间和浓度依赖性抑制人食管癌Eca109细胞的生长,作用72h后,对细胞生长的抑制率可达85.95%,凋亡率由(2.38±0.42)%增加到(48.46±0.73)%;50～400μmol/L时增殖指数和S期的细胞比例则明显降低,G0/G1期的细胞比例增加;同时,低浓度的戊地昔布对COX-2mRNA及蛋白的表达均没有影响,随着浓度的增加明显抑制COX-2mRNA及蛋白的表达。结论:戊地昔布可诱导人食管癌Eca109细胞发生凋亡,其诱导凋亡的机制可能与抑制COX-2的表达有关。     

环氧合酶-2与肿瘤的侵袭和转移

环氧合酶-2是花生四稀酸转化为前列腺素过程的关键限速酶，近几年的研究表明，它在肿瘤组织中均有表达。其与肿瘤的侵袭和转移的关系受到越来越多的关注。本文从NCBI检索文献，查阅相关的资料对COX-2与肿瘤的侵袭和转移的关系进行了综述。主要从细胞凋亡、肿瘤的血管生成、肿瘤细胞的侵袭性及细胞外机制四方面进行了综述。发现COX-2的表达可抑制细胞的凋亡、促进肿瘤的血管生成而促进肿瘤细胞的生长。COX-2的表达可直接促进肿瘤细胞的侵袭。COX-2的表达与细胞外机制的改变也有明显的相关关系。COX-2的表达可上调MMP-2及MMP-9，给予COX-2抑制剂可抑制基质金属蛋白酶的表达。COX-2的表达还可影响黏附分子的表达，促进内皮细胞的伸展。COX-2的这些作用可被COX-2的抑制剂，尤其是选择性抑制剂所抑制．这就为将C0X-2抑制剂用于肿瘤的抗转移治疗和化学预防提供了广阔的前景。     

调节环氧化酶-2治疗肿瘤的前景

环氧化酶-2(cyclooxygenase，COX-2)高表达与肠癌、乳腺癌、卵巢癌和头颈癌等恶性肿瘤的发生、发展有关。研究发现，COX-2通过抑制细胞凋亡和促进肿瘤血管增生，参与肿瘤的发生、发展。目前研究结果显示，化疗、放疗与COX-2抑制剂以及其他有关因素结合的综合治疗具有很大的发展前途。     

食管癌组织中COX-2、p53和PCNA的表达及意义

目的 :研究食管癌组织中环氧合酶 2 (COX 2 )、p53和增殖细胞核抗原 (PCNA)的表达及意义。方法 :采用免疫组化染色 (EnVision及S P)法 ,检测 82例食管鳞状细胞癌、2 0例食管炎和 1 6例正常食管粘膜组织标本中COX 2、P53和PCNA的表达。结果 :82例食管癌组织中COX 2、p53和PCNA的阳性表达率分别为 87.8% (72 82 ) ,82 .9% (68 82 )和 95 .1 % (78 82 ) ,而癌旁及正常组织中均呈阴性表达。COX 2在高分化和中分化食管癌中的表达率显著高于低分化癌 (P <0 .0 1 ) ;无淋巴结转移者表达率高于有淋巴结转移者 (P <0 .0 5)。p53的过表达与浸润深度和淋巴结转移呈正相关 (P <0 .0 1 )。结论 :COX 2、P53和PCNA的过表达可能均参与了食管癌的发生发展过程     

卵巢上皮恶性肿瘤组织中环氧合酶-2的表达及其意义

目的:探讨环氧合酶-2 蛋白(COX-2)在卵巢上皮癌组织中的表达及与临床病理参数的关系。方法:应用免疫组织化学方法检测石蜡切片的27例卵巢上皮癌组织中COX-2蛋白的表达。结果:正常卵巢上皮组织中未显示COX-2蛋白的表达;在66.7 %(18/27)卵巢上皮癌组织中COX-2蛋白呈高表达。COX-2表达与卵巢上皮癌临床分期、组织类型及有无淋巴结转移无关(P>0.05)。高分化卵巢上皮癌组织COX-2蛋白的表达显著高于低分化的癌组织(P<0.05)。结论:COX-2蛋白可能主要参与高分化卵巢上皮癌的致癌过程。     

A study on cyclooxygenase -2 protein expression in esophageal caiconogenesis

To investigate cyclooxygenesis-2(Cox-2) protein expression in esophageal carcinogenesis, especially in esophageal squamous-cell carcinoma, and discuss the infeasibility with the nonsteroidal anti-inflammatory drug(NSAIDS) for the high-risk population of esophageal carcinomas, two hundred sixty three biopsy and esophaectomy specimens which include the normal esophageal mucosa, hyperplasia, displasia from mild to severe, carcinoma in situ and invasive cancer were examined for Cox-2 protein exp…     

上消化道肿瘤端粒酶活性研究

目的 探讨端粒酶活性与消化道肿瘤发生的关系。方法 采用ＥＬＩＳＡ免疫组化法检测端粒酶的活性,对８７例上消化道癌和２７例癌旁正常粘膜进行对比性研究。结果 食管癌端粒酶检测的阳性率为８１．５％（４４／５５）,癌旁正常粘膜为１７．６％（３／１７）;贲门癌阳性率为１００．０％（１２／１２）;胃癌阳性率为８５．７％（１８／２１）,癌旁正常粘膜为２０．０％（２／１０）。结果表明食管癌及胃癌与其相应的癌旁组织中     

食管癌发生发展过程中环氧合酶-2蛋白表达的研究

目的 研究环氧合酶－2（Cox-2)蛋白在食管癌及癌前病变组织中的表达,探讨非类固醇抗炎药在食管癌高危人群中化学预防的可能性。方法 应用免疫组织化学方法检测120例食管癌（原位癌30例,鳞状细胞癌60例,腺癌30例）及其113例增生性病变（单纯增生29例,轻、中、重度不典型增生分别为31例、30例、23例）和27例正常食管黏膜鳞状上皮,以及3例Barrett食管组织中Cox-2蛋白的表达情况。结果 在正常食管黏膜上皮,单纯增生,轻、中、重度不典型增生,原位癌未发现有Cox-2蛋白表达;在6％（4／60）侵袭性鳞状细胞癌和70％（21／30）的食管腺癌中,Cox-2蛋白表达阳性。结论 Cox-2蛋白表达可能与食管腺癌的形成有关,而与鳞状细胞癌的发生发展无关。     

The effects of L-748706, a selective cyclooxygenase-2 inhibitor, on N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis

Epidemiological studies suggest that the frequent intake of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a decreased risk of developing esophageal squamous cell carcinoma (SCC). This decrease is thought to correlate with the inhibition of cyclooxygenase (COX) activity. The production of prostaglandin E2 (PGE2), a major metabolite of COX, is increased in numerous human cancers including esophageal SCC, therefore, inhibition of COX activity and subsequent suppression of the formation of PGE2 may be chemopreventive in the esophagus. The objective of the present study was to determine whether L-748706 (L-706), a novel selective COX-2 inhibitor, would prevent N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumor progression in the Fischer 344 (F344) rat. In rats pretreated with a low-dose of NMBA (0.25 mg/kg body weight), L-706 at 100 p.p.m. in the diet significantly reduced tumor multiplicity but not tumor incidence. At 150 p.p.m. in the diet, L-706 alone and in combination with 200 p.p.m. piroxicam produced significant reductions in both tumor incidence and multiplicity. Inhibition of tumor development in low-dose NMBA-treated rats was associated with reductions in esophageal cell proliferation rates and PGE2 levels in preneoplastic tissues. In contrast, in rats treated with a higher dose of NMBA (0.5 mg/kg body weight), neither L-706 alone nor in combination with piroxicam reduced esophageal tumor incidence or multiplicity in spite of the fact that they reduced esophageal PGE2 levels in preneoplastic tissues and in papillomas. Cell proliferation rates were reduced only in animals treated with L-706 + piroxicam. Our data suggest that the chemopreventive treatments were effective in inhibiting tumor development in NMBA-treated animals only when they reduced PGE2 levels in preneoplastic esophageal tissues approximately to those levels found in normal esophagus.     

食管癌中P—糖蛋白表达及其临床病理意义

目的：研究食管癌中Ｐ－糖蛋白表达的意义。方法：采用免疫组化方法检测５２例食管癌、９例鳞状上皮不典型增生及２６例正常食管组织中Ｐ－糖蛋白的表达。结果：６０％的食管癌、３３％的不典型增生及１２％正常食管组织中均有阳性表达。食管癌中Ｐ－糖蛋白表达与组织类型相关。结论：Ｐ－糖蛋白的表达参与了食管癌天然性耐药的产生，可作为指导临床化疗的参考指标     

Piroxicam is an ineffective inhibitor of N-nitrosomethylbenzylamine-induced tumorigenesis in the rat esophagus

Epidemiological studies indicate an association between the frequent use of nonsteroidal anti-inflammatory drugs and decreased risk for esophageal cancer. These studies suggest that limiting excess prostaglandin production, via inhibition of cyclooxygenase (COX)-mediated arachidonic acid metabolism, may be an important strategy for the prevention of this type of malignancy. N-Nitrosomethylbenzylamine (NMBA)-induced tumorigenesis in the rat esophagus is a model of human esophageal squamous cell carcinoma used for investigations of chemical carcinogenesis and for the evaluation of putative chemopreventive agents. In this study, we characterized COX-mediated arachidonic acid metabolism in NMBA-induced rat esophageal tumorigenesis by measuring COX-1 and COX-2 expression and prostaglandin E(2) production. In addition, we evaluated the ability of piroxicam, a potent COX inhibitor, to prevent postinitiation events of NMBA-induced tumorigenesis in the rat esophagus. After a 2-week acclimatization period, groups of 30 male F344 rats received s.c. injections of NMBA (0.5 mg/kg b.w.) three times/week for 5 weeks. Seventy-two h after the final NMBA treatment and for the remainder of the study, piroxicam was administered in the diet at 200 and 400 ppm. Twenty-five weeks after the initiation of NMBA treatment, we observed an elevation in COX mRNA and protein expression and prostaglandin E(2) production in NMBA-treated esophageal tissues compared with normal epithelium. However, these changes were associated with data indicating that a COX inhibitor is not preventive in NMBA-induced rat esophageal tumorigenesis. Administration of piroxicam in the diet produced no significant reductions in esophageal tumor incidence, multiplicity, or size. The reasons for the lack of effect are largely unknown but may be related to the inability of piroxicam to modulate other biochemical pathways involved in NMBA-induced tumorigenesis.     

环氧合酶-2与乳腺癌的研究进展

环氧合酶（cyclcoxygenase,COX）是花生四烯酸合成前列腺素的限速酶。COX-2在多种肿瘤中表达上涮,通过多种机制参与肿瘤的发生、发展和转移。近年来,COX-2与乳腺癌的关系研究逐渐成为乳腺癌治疗的新靶点。