UP－REGULATION OF CYCLOOXYGENASE－2 GENE EXPRESSION CORRELATES WITH TUMOR ANGIOGENESIS IN HUMAN BREAST CANCER

Prostaglandins(PGs) play a critical role in tumor development and growth by regulating numerous biologic processes, including tumor angiogenesis[1]. Cyclooxygenase-2 (COX-2) is an inducible enzyme that converts arachidonic acid to PGs. Overexpression of the COX-2 gene in mammary glands of transgenic mice was sufficient to induce tumorigenesis[2]. COX-2expression may contribute to the synthesis of PGs, which have been related to carcinogenesis and tumor progression. Recent studies have sh…     

Correlation between cyclooxygenase-2 and tumor angiogenesis in non-small cell lung cancer

The role of COX-2 expression and angiogenesis of lung cancer is yet to be delineated. Eighty four non-small cell lung cancer (NSCLC) specimens were evaluated for COX-2 expression, microvessel density (MVD), and vascular endothelial growth factor (VEGF) expression by immunohistochemical methods. The relationships between COX-2 expression and MVD, VEGF expression, and survival time were analyzed. COX-2 expression was observed in the cytoplasm and membrane of the carcinoma cells, and premalignant cells. COX-2 was positive in 67 cases (79.8%). There was a statistically significant correlation between COX-2 expression and tumor size, TNM stage, tumor type, VEGF expression, and vascular pattern with survival in univariate analysis. No significant correlation was seen between COX-2, VEGF expression and MVD. A lack of expression of either COX-2 or VEGF expression or both, however, was associated with lower MVD than the group with both expressed. The difference was statistically significant (P=0.005). Statistically significant differences were also observed according to TNM stage, vascular pattern, COX-2 expression, and VEGF expression. With multivariate analysis, only TNM stage and COX-2 expression retained their significance as independent predictors of survival. COX-2 expression takes part in tumor angiogenesis and is a significant poor prognostic factor in the surgically resected NSCLC. COX-2 inhibitor, either in combination therapy with other agents, or for chemoprevention, may be effective via suppression of angiogenesis in this fatal disease.     

Association of cyclooxygenase-2 and matrix metalloproteinase-2 expression in human breast cancer

Summary Expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-2 (MMP-2) associates with reduced survival in human breast cancer. COX-2 may be directly involved with mammary carcinogenesis, since expression of COX-2 is sufficient for formation of breast tumors in transgenic mice, and COX-2 selective inhibitors can suppress tumorigenesis in rodent models of breast cancer. MMP-2 is an extracellular matrix degrading proteolytic enzyme that bas been linked to invasion and metastasis. A direct link between COX-2 and MMP-2 may exist, since inhibition of COX-2 activity can result in reduction of MMP-2 expression and activity. In this study we analyzed protein expression of COX-2 and MMP-2 in tissue array specimens of 278 invasive breast cancers by immunohistochemistry. Immunopositivity of these two markers was correlated with each other and with various clinicopathological parameters including survival. We found high COX-2 expression in 30% and high MMP-2 expression in 83% of the breast cancer specimens, and there was a positive association between the expression of these two factors (p=0.003). It was especially evident that whenever COX-2 expression was high, MMP-2 expression was almost invariably high (95%). Furthermore, high expression of either COX-2 or MMP-2 associated with decreased disease specific survival when compared with the COX-2 or MPP-2 low group (p=0.026 and p=0.021, respectively). Taken together, our results indicate that expression of COX-2 protein is associated with expression of MMP-2 protein in human breast cancer and that both COX-2 and MMP-2 are markers of poor prognosis in breast cancer.     

The association between a mutated ras gene and cyclooxygenase-2 expression in human breast cancer cell lines.

Cyclooxygenase (COX) is rate-limiting for arachidonic acid metabolism to the prostanoid family of eicosanoids. Some human breast cancers, notably those which are estrogen receptor (ER)-negative with high metastatic potential, produce high levels of prostaglandin E2 (PGE2). In some cell types, expression of the inducible COX-2 isoform occurred in association with a ras gene mutation. We determined COX-1 and COX-2 expression, and the corresponding PGE2 secretions, in 4 ER-negative human breast cancer cell lines, the MCF10A breast epithelial cell line, and the same non-cancerous line transfected with a mutated ras gene. The highly invasive MDA-MB-231 and Hs578T cancer cell lines, which possess a mutated Ki-ras and H-ras, respectively, expressed constitutive and inducible COX-2, and produced high PGE2 levels; the less invasive MDA-MB-435 and SK-BR-3 lines, without a mutated ras, possessed only low levels of COX-2, and secreted correspondingly low PGE2 levels. Similarly, the ras transfectant, but not parental MCF10A cells, expressed inducible COX-2. Chemosuppression with a selective COX-2 inhibitor may be effective only in that minority of breast cancers which have a mutated ras gene.     

乳腺癌组织中HER-2的表达与肿瘤超声声像图特征的相关性

目的:探讨乳腺癌组织中HER-2的表达与肿瘤超声声像图特征及其弹性硬度的相关性。方法:收集2016年5月至2019年5月于我院就诊并确诊的282例乳腺癌患者,采用免疫组化法检测HER-2的表达水平,所有乳腺癌均行常规超声及弹性超声检查。分析乳腺癌二维声像图、血流及弹性特征与HER-2表达的相关性,并比较它们在HER-2阳性和HER-2阴性组之间的差异。统计学方法采用Pearson相关性分析及卡方检验。结果:乳腺癌的声像图特征多呈现为形态不规则、边缘不光整,以后方衰减、微小钙化发生、血流分级0-2级、淋巴结转移、组织弹性硬为主。相关性分析显示,HER-2表达阳性与乳腺癌肿瘤边缘光整程度、肿瘤边界、后方衰减具有显著的正相关性（P＜0.05）。结论:HER-2阳性表达与乳腺癌患者的乳腺超声特征显著相关,可作为乳腺癌诊断的指标。     

肝细胞癌COX-2表达与新生血管生成关系的研究

目的:探讨环氧合酶2(cyclooxygenase2,COX2)表达上调与人肝细胞癌(HCC)新生血管生成的关系。方法:2002～2003年本院病理诊断为HCC的80例手术标本,采用免疫组化方法,检测癌组织中COX2和血管内皮生长因子(Vascularendothelialgrowthfactor,VEGF)和CD34的表达情况,使用Weidner分析方法来计算CD34标记的肿瘤微血管密度(microvasculardensity,MVD)。结果:COX2和VEGF在HCC中表达率分别为75.00%(60/80)和62.50%(50/80)。VEGF在COX2强阳性组和中弱阳性组的免疫染色积分分别是5.98±1.16和3.30±0.22;VEGF在COX2强阳性组和中弱阳性组的表达率分别是71.43%(25/35)和28.00%(7/25),两组间差异非常显著(P<0.01),COX2与VEGF表达有明显相关性(P<0.01)。MVD在COX2强阳性组和中弱阳性组的评分分别为73.81±12.43和33.42±7.52,两组间差异非常显著(P<0.01),COX2与MVD有明显相关性(P<0.01)。结论:COX2高表达与HCC血管生成密切相关。     

Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer

Cyclooxygenase-2 (Cox-2) expression can induce mammary tumorigenesis in transgenic mice, and selective Cox-2 inhibitors are both chemopreventive and chemotherapeutic in rat models of breast cancer. We analyzed the expression of Cox-2 protein by immunohistochemistry in tissue array specimens of 1576 invasive breast cancers. Moderate to strong (elevated) expression of Cox-2 protein was observed in 37.4% of the tumors, and it was associated with unfavorable distant disease-free survival (P < 0.0001). Elevated Cox-2 expression was associated with a large tumor size, a high histological grade, a negative hormone receptor status, a high proliferation rate (identified by Ki-67), high p53 expression, and the presence of HER-2 oncogene amplification (P < 0.0001 for all comparisons), along with axillary node metastases and a ductal type of histology (P = 0.0001 and P = 0.0017, respectively). Interestingly, association with the unfavorable outcome was especially apparent in the subgroups defined by estrogen receptor positivity, low p53 expression, and no HER-2 amplification (P < 0.0001 for all comparisons). These results indicate that elevated Cox-2 expression is more common in breast cancers with poor prognostic characteristics and is associated with an unfavorable outcome. The present findings support efforts to initiate clinical trials on the efficacy of Cox-2 inhibitors in adjuvant treatment of breast cancer.     

乳腺癌组织中COX-2与MDR1/P-gp表达的相关性研究

目的:探讨环氧化酶-2(COX-2)蛋白与P糖蛋白(P-gp)在乳腺癌组织中表达的相关性。方法:应用免疫组织化学染色法,检测32例乳腺癌组织中COX-2蛋白与P-gp蛋白的表达情况。结果:32例乳腺癌组织中COX-2表达阳性率为62·5%(20/32),P-gp表达阳性率为46·9%(15/32),两者表达呈正相关性(r=0·598,P<0·05)。结论:乳腺癌组织中COX-2与P-gp表达呈正相关,COX-2可干预P-gp的表达并参与乳腺癌多药耐药(MDR)的调节。     

乙酰肝素酶在乳腺癌组织中的表达与肿瘤血管形成及预后的关系

背景与目的:乙酰肝素酶是一类裂解硫酸乙酰肝素的糖苷内切酶,通过降解肿瘤细胞胞外基质及基底膜和促进新生血管形成加速肿瘤扩散和转移。本研究探讨乳腺癌组织中乙酰肝素酶表达与血管生成及预后的关系。方法:采用免疫组化方法,分别应用乙酰肝素酶抗体及CD34单克隆抗体检测120例浸润性乳腺癌组织中乙酰肝素酶的表达和微血管密度(microvesseldensity,MVD),并与患者年龄、肿瘤大小、组织学分级、腋淋巴结转移、临床分期及5年生存率进行相关分析。统计学分析采用χ2检验和t检验、Kaplan-Meier及log-rank检验。结果:①乳腺癌组织中乙酰肝素酶的阳性率为65%,与正常乳腺组织中的阳性率有显著性差异(P<0.05);乳腺癌组织中MVD值为53.84±13.45,显著高于正常对照组(33.32±8.55)(P<0.01)。②乙酰肝素酶的表达与乳腺癌肿瘤大小、组织学分级及腋淋巴结转移率、临床分期、5年生存率密切相关(P<0.05)。③乙酰肝素酶的表达与乳腺癌血管生成有关,乙酰肝素酶高表达组MVD值大于低表达组(P<0.05),两者呈显著正相关(r=0.358,P<0.05)。结论:乙酰肝素酶与乳腺癌血管形成及预后关系密切。     

乳腺癌微环境中巨噬细胞相关因子与环氧化酶-2的调节

肿瘤微环境中浸润的巨噬细胞(tumor-associated macrophages, TAMs)是近年来癌症治疗的新靶点。TAMs通过分泌大量促癌细胞因子如血管内皮生长因子、白细胞介素、基质金属蛋白酶等, 促进肿瘤细胞增殖、侵袭和转移。炎症因子环氧化酶-2(cyclooxygenase-2, COX-2)参与了微环境中血管形成和免疫调节, 加速肿瘤进程, 也是乳腺癌治疗的有力靶点。而COX-2抑制剂如塞来昔布, 在抑制TAMs活性和改善肿瘤微环境方面具有较大潜力。因此, 本文就乳腺癌微环境中TAMs分泌的重要细胞因子与COX-2的相互关系加以讨论, 分析其对应的拮抗剂单独或与COX-2抑制剂联合的使用价值, 旨在为选择多靶点联合阻断TAMs活性的研究提供理论基础, 也为乳腺癌的生物靶向治疗提供新方向。      

环氧化酶-2与乳腺癌关系的研究进展

最近的研究表明环氧化酶-2(COX-2)的表达不但与乳腺癌的发生、发展相关，而且其表达程度与进展性乳腺癌的病理参数及预后存在相关性，一些应用COX-2抑制剂防治乳腺癌的实验和临床研究也正成为当前的研究热点。     

Clinical implications of expression of cyclooxygenase-2 related to angiogenesis in ovarian cancer

Angiogenesis is essential for the development, growth and advancement of solid tumors. Cyclooxygenase (cox)-2 is recognized as an angiogenic factor in various tumors. This prompted us to study the clinical implications of cox-2 expression and angiogenesis in ovarian cancer. There was a significant correlation between microvessel counts and cox-2 levels. Cox-2 localized in the cancer cells, but not in the stromal cells of ovarian cancer tissue. Cox-2 levels increased with the advancement, and the prognosis of the 30 patients with high cox-2 expression was extremely poor (33%), while the 24-month survival rate of the other 30 patients, those with low cox-2 expression, was 67%. Furthermore, cox-2 levels significantly correlated with VEGF levels. VEGF associated with cox-2 might work on angiogenesis with advancement. Therefore, long-term administration of cox-2 inhibitors might be effective on the suppression of regrowth or recurrence after intensive treatment for advanced ovarian cancer.     

Elevated cyclooxygenase-2 expression correlates with distant metastases in breast cancer

BACKGROUND: Cyclooxygenase-2 (COX-2) overexpression clearly plays an important role in the pathogenesis of breast cancer. In this study, we analysed the relationship between COX-2 expression and various clinicopathological factors in human breast cancer. MATERIALS AND METHODS: Using immunohistochemistry, we analysed archival specimens of human breast cancer (n=29) using antibodies to COX-2, ER, PgR and HER2 and, from medical records, obtained clinicopathological data. RESULTS: We observed a significant association between COX-2 overexpression and distant metastasis. COX-2 expression was not significantly associated with any other clinical or pathological variable. CONCLUSION: These findings lend support to the hypothesis that COX-2 overexpression represents an adverse prognostic event in human breast cancer and are encouraging for proposed strategies of COX-2 suppression to treat the disease.     

三叶因子3在胃癌组织中的表达及与血管形成的关系

目的　研究三叶肽因子 3(trefoilfactor3,TFF3)在人胃癌组织中的表达及其与胃癌血管形成的关系。方法　应用免疫组织化学S-P法检测 40例原发性胃癌及 10例正常胃粘膜组织中TFF3的表达,同时检测微血管密度(microvesseldensity,MVD),以抗CD34标记。结果　10例正常胃黏膜组织TFF3全部阴性表达, 40例胃癌组织TFF3表达阳性率为 60% (24 /40)。其阳性表达与胃癌的淋巴结转移有关 (P<0. 05),而与性别、肿瘤的浸润程度、细胞的分化程度无关.胃癌组织MVD明显高于正常胃粘膜组织,TFF3阳性及阴性表达组MVD均值分别为 32. 71±8. 04、26. 94±9. 08,两组间MVD均值差异有统计学意义 (P<0. 05)。结论　胃癌组织中TFF3表达增高,其高表达与淋巴结转移,肿瘤微血管形成有关。     

食管鳞癌组织环氧化酶-2表达与血管生成相关性的研究

目的:研究食管鳞状细胞癌组织中环氧化酶-2(COX-2)、碱性成纤维细胞生长因子(b-FGF)表达情况与食管癌病理特征的关系。方法:采用免疫组织化学(SP)法检测58例食管鳞癌组织中COX-2、b-FGF及CD34蛋白的表达。结果:58例患者食管鳞癌组织中,COX-2、b-FGF均高表达,阳性表达率分别为70.6%和75.9%,而MVD为46.71±11.65,COX-2、b-FGF蛋白表达与性别、分期、淋巴结转移无关(P均>0.05),COX-2、CD34与肿瘤的分化程度有关(P均<0.05)。COX-2与b-FGF表达及微血管密度(MVD)无相关(P均>0.05)。结论:COX-2、b-FGF在食管鳞癌组织中高表达,可能在食管癌的发生发展中起关键作用,两者联合检测对食管癌的诊断有一定价值。     

Heparanase、COX-2在肾癌中的表达和肿瘤血管生成的关系

目的:探讨Heparanase、COX-2在肾癌中表达的相关性及与肿瘤血管生成的关系及意义。方法:采用免疫组化PV6000法检测54例肾癌和20例正常肾脏组织中Hpa、COX-2蛋白的表达,以CD34单克隆抗体进行微血管内皮染色,计算微血管密度,分析Hpa、COX-2在肾癌中表达的相关性以及与临床病理特征及微血管密度的关系。结果:Hpa、COX-2在肾癌中的表达均较正常肾脏组织明显增高(P<0.05)。Hpa的表达与肾癌的临床分期、肿瘤大小、远处转移有关(P<0.05),而与患者年龄、性别、肿瘤的分化程度无相关性(P>0.05)。COX-2的表达与肾癌的临床分期、远处转移及分化程度有关(P<0.05),与患者年龄、性别、肿瘤大小无关(P>0.05)。肾癌组织中MVD显著高于正常肾脏组织(P<0.05),高MVD组中Hpa、COX-2表达的阳性率高于低MVD组(P<0.05),Hpa、COX-2阳性表达组中MVD值亦高于阴性表达组(P<0.05)。Hpa、COX-2的表达具有相关性(P<0.05)。结论:Hpa、COX-2可能通过促肿瘤血管生成参与肾癌的恶性生物学行为,并有可能成为判断肾癌预后的指标和靶向治疗的靶点。     

乳腺癌组织中环氧化酶-2 mRNA的表达及其临床病理意义

目的：探讨环氧化酶－2（COX－2）mRNA在乳腺癌中的表达以及与乳腺癌临床病理特征的关系。方法：以β-actin基因为参照,应用逆转录聚合酶链反应（RT－PCR）技术,检测30例乳腺癌组织及癌旁正常腺体中COX－2 mRNA的表达。应用条带密度分析软件,定量分析RT－PCR产物电泳带密度。结果：30例癌组织中,28例COX－2 mRNA表达水平明显增高,全距为0.05-0.91,中位数为0.53;癌旁正常腺体中无表达或表达很弱,全距为0－0.09,中位数为0。癌组织与正常腺体中COX－2的表达差异有显著性（P＜0．05）。COX－2的高表达与淋巴结的转移有关（P＜0．05）,而与年龄、癌肿的大小、临床病理分期、病理类型无关（P＞0．05）。结论：乳腺癌组织中COX－2 mRNA表达水平高于正常腺体,其表达与乳腺癌的发生、发展及淋巴结转移有关。