塞来昔布诱导人胃癌细胞凋亡抑制新生血管形成

目的 探讨环氧合酶2(COX-2)抑制剂塞来昔布对人胃癌细胞增殖和新生血管形成的抑制作用.方法 将59例胃癌患者随机分为试验组(37例)和对照组(22例),试验组术前给予常规剂量塞来昔布,共7d,然后行手术治疗;对照组行单纯手术治疗.免疫组化法检测胃癌组织中COX-2和血管内皮生长因子(VEGF)的表达及微血管密度(MVD),DNA末端原位标记染色法检测胃癌细胞凋亡.以20例健康人作为正常对照.结果 试验组胃癌细胞凋亡率为7.1%±1.0%,显著高于对照组(6.2%±0.9%,P<0.05).试验组和对照组中,COX-2阳性表达分别为16例(43.2%)和17例(77.3%),VEGF阳性表达分别为17例(45.9%)和16例(72.7%),差异均有统计学意义(P<0.05).试验组MVD为30.48±5.02,显著低于对照组(38.98±4.58,P<0.05).结论 塞来昔布可诱导人胃癌细胞凋亡,抑制胃癌新生血管形成.     

Clinicopathological significance of E-cadherin, VEGF, and MMPs in gastric cancer

E-cadherin, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs) are important molecules involved in tumor metastasis. In this study, we examined the expressions of E-cadherin, VEGF, MMP-1, MMP-2, and microvessel density (MVD), as well as microlymphatic vessel density (MLVD) in 200 cases of gastric cancer tissues, and determined the relationship between these parameters and the clinicopathological features and patient survival. Protein expressions, MVD, and MLVD were detected by immunohistochemistry. The correlation between the expression levels of these molecules and the clinicopathological features was analyzed. Patient survival was estimated by Kaplan and Meier analysis. Compared to normal gastric mucosa, expression of E-cadherin was reduced in 78% of gastric cancer tissues and 44.6% of adjacent non-cancerous gastric tissues. VEGF was positive in 81.5% of gastric cancer tissues, 35.7% of adjacent non-cancerous gastric tissues, and 10% of normal gastric mucosa. MMP-1 was positive in 80.5% of gastric cancer tissues, 69.6% of adjacent non-cancerous gastric tissues, and 20% of normal gastric mucosa. Reduced expression of E-cadherin was closely correlated with poor tumor differentiation and a deeper tumor invasion. Increased expressions of VEGF and MMP-1 were closely linked with poor differentiation and Lauren classification. Increased expression of MMP-2 was closely correlated with more lymph node metastasis, a deeper invasion, and a larger tumor size. More MVD was observed in VEGF-positive tissues than in VEGF negative tissues. Therefore, abnormal expressions of E-cadherin, VEGF, MMP-1, and MMP-2 are widely present in gastric cancer tissues. Abnormal expressions of E-cadherin, VEGF, and MMP-2 may represent the early molecular changes in the development of gastric cancer. Positive expression of E-cadherin and negative expression of VEGF and MMP-2 are correlated with a better patient survival.     

Positive correlation of osteopontin, cyclooxygenase-2 and vascular endothelial growth factor in gastric cancer

Osteopontin (OPN), cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are overexpressed in various experimental models of malignancy. However, the correlation and role of the three molecules in gastric cancer is unclear. In the present study, we found that OPN, COX-2 and VEGF were overexpressed in 53 cancerous tissues with gastric cancer compared with 40 normal mucosa tissues by immunohistochemistry method. Moreover, the results indicated co-expression of OPN, COX-2, and VEGF in gastric cancer. Levels of OPN, COX-2, and VEGF were all significantly correlated with TNM stage, lymph node metastasis and distant metastasis (P < 0.05), while not related to prognosis of patients. In addition, individual levels of OPN, COX-2, and VEGF were all significantly correlated with microvessel density (MVD), valued by CD34 staining directly with r-values of 0.416, 0.400, and 0.566, respectively (P < 0.01). Both OPN and COX-2 levels showed a positive correlation with VEGF (P < 0.05). Meanwhile, expression of COX-2 is in relation to OPN (P < 0.01). Overall, survival for patients with high MVD was significantly lower than for patients with low MVD (P < 0.05). Our findings indicate that OPN, COX-2, and VEGF synergically promote angiogenesis and metastasis in gastric cancer. It may be an important and useful strategy to target these molecules for prevention and therapy of tumor.     

COX-2、VEGF在胃癌中的表达及其预后意义

目的 :研究COX 2、VEGF表达对胃癌的预后意义。方法 :收集我院 1990～ 1999年早、中期胃癌 2 81例 ,对有完整存档蜡块资料的 2 32例进行免疫组织化学染色。检测COX 2、VEGF及MVD在胃癌组织中的表达 ,并分析其预后意义。结果 :胃癌组织中COX 2、VEGF阳性表达的MVD值均显著高于COX 2、VEGF阴性表达者(P <0 0 1) ;COX 2、VEGF阳性表达及MVD值与胃癌淋巴结转移、血管浸润均密切相关 (P <0 0 1) ;COX 2、VEGF阳性表达者五年生存率明显低于阴性者 (P <0 0 1)。多因素分析显示 ,VEGF表达、淋巴结转移、COX 2表达、浸润深度、血管浸润均为胃癌独立的预后因素。结论 :COX 2、VEGF在胃癌组织呈过度表达状态 ,与胃癌的生长和浸润转移关系密切 ,可以作为反映胃癌生物学行为和判断预后的有效指标。     

胃癌组织中COX-2和VEGF表达及其相关性研究

目的探讨环氧合酶2(cyclooxygenase-2,COX-2)和血管内皮生长因子(vascularendothelial growthfactor,VEGF)在人胃癌组织中表达及其相关性。方法应用免疫组织化学SABC法检测53例人胃癌组织中COX-2、VEGF和CD34的表达,并以40例正常胃粘膜标本作为对照。对CD34阳性血管进行微血管密度(microvesseldensity,MVD)计数。对COX-2和VEGF的表达采用半定量计分法判定,并结合临床资料进行统计学分析。结果53例人胃癌组织中,COX-2表达阳性者44例,阳性率为83.0%;VEGF表达阳性者45例,阳性率为84.9%。COX-2表达与VEGF表达相关显著(P<0.05)。并且,COX-2和VEGF的表达与TNM分期(P<0.05,P<0.05)、淋巴结转移(P<0.01,P<0.05)和远处转移(P<0.01,P<0.05)相关。COX-2/VEGF同高表达组中MVD值(79.5±25.8)高于COX-2/VEGF同低表达组中的MVD值(45.0±13.9),差异非常显著(P<0.01)。结论胃癌组织中COX-2与VEGF共表达,并相互协同促进肿瘤血管生成和转移。     

Antitumor and anti-metastatic effects of cyclooxygenase-2 inhibition by celecoxib on human colorectal carcinoma xenografts in nude mouse rectum

We examined the effects of the preferential cyclooxygenase-2 (COX-2) inhibitor celecoxib on tumorigenesis, angiogenesis, apoptosis, vascular endothelial growth factor (VEGF) protein expression and metastasis in HT-29 human colorectal carcinoma cell xenografts in nude mouse rectum. COX-2 mRNA expression was examined in the xenograft and metastatic sites. The antitumor effect of celecoxib in the xenografts was evaluated by measuring the weight of the peri-ano-rectal tumor. The anti-metastatic effect of celecoxib was assessed by quantification of lymph node and lung metastases by amplification of a cancer-related human DNA by TaqMan PCR. The effects of celecoxib on angiogenesis, apoptosis, prostaglandin E2 (PGE2) production and VEGF protein expression in the xenografts were evaluated by means of microvessel density (MVD) counting, terminal deoxynucleotidyl transferase-mediated nick end labeling assay, quantitative enzyme-linked immunosorbent assay and western blotting, respectively. The rectal xenograft model showed lymph node and lung metastases with enhanced expression of COX-2 mRNA in each organ. Celecoxib inhibited rectal xenograft growth in a dose-dependent manner as follows: 150?ppm, 33.0% (p=0.000220); 750?ppm, 46.4% (p=0.0000292); 1500?ppm, 63.4% (p=0.0000109). Celecoxib inhibited lymph node metastasis in a dose-dependent manner as follows: 150?ppm, 86.7% (p=0.0263); 750?ppm, 90.3% (p=0.00638); 1500?ppm, 96.0% (p=0.000894). Celecoxib also inhibited lung metastasis as follows: 750?ppm, 53.3% (p=0.0107); 1500?ppm, 78.3% (p=0.00022). Celecoxib (1500?ppm) significantly inhibited PGE2 production by 68.4% (p=0.000157) and MVD counting by 48.2% (p=1.3x10-12) and induced apoptosis 2.5-fold (p=3.0x10-14) in the rectal xenograft. Celecoxib suppressed VEGF protein expression in the rectal xenograft. These studies demonstrate that celecoxib reduces the growth and metastatic potential of colorectal carcinoma in mice through COX-2 inhibition, anti-angiogenesis and apoptosis induction. The studies using HT-29 human colorectal carcinoma cell xenografts in nude mouse rectum also provide important information that supports that the COX-2 inhibitor celecoxib has a high potential for use as a clinical agent for inhibition of hematological and lymphatic metastases of colorectal cancer.     

A case report of disseminated malignant mesothelioma of peritoneum responding remarkably to thalidomide, celecoxib, vinorelbine and CDDP

Malignant mesothelioma (MM) is a rare neoplasm that is commonly fatal within 12-17 months after diagnosis. There are no widely accepted curative approaches. It recurs even after the most aggressive surgical resection. MM is resistant to chemotherapy and radiation. Most of the chemotherapeutics have been evaluated in MM, however, no drugs have a response rate greater than 20%. The combination of drugs has no increased efficacy compared with single agents. Vinorelbine has useful clinical activity against MM with a response rate of 24%. Vascular endothelial growth factor (VEGF) is expressed in MM and pleural effusion of MM. There is a significant inverse correlation between serum VEGF levels and MM patient survival. Cyclooxygenase-2 (COX-2) is expressed in MM. COX-2 plays an important role in tumor growth, invasion, and angiogenesis. VEGF and COX-2 are potential targets in MM. The downregulation of bFGF, VEGF, and maybe some other angiogenesis stimulators, is one of the antiangiogenic mechanisms of thalidomide. Celecoxib is a potent selective COX-2 inhibitor. Here we report a case of disseminated malignant mesothelioma of peritoneum responding remarkably to thalidomide, celecoxib, vinorelbine and CDDP.     

Cyclooxygenase-2 upregulates vascular endothelial growth factor expression and angiogenesis in human gastric carcinoma

Although gastric cancer with cyclooxygenase (COX)-2 overexpression is associated with poor prognosis, the mechanistic pathway remains unknown. We examined the associations between expressions of COX-2 and vascular endothelial growth factor (VEGF) in both gastric cancer cells and in human gastric cancer. The gastric cell line, Kato III, was transiently transfected with cox-2 expressing vector. The levels of COX-2, prostaglandin (PG) E2 and VEGF expression were measured post-transfection. Additionally, expressions of COX-2 and VEGF in human gastric cancer were determined by immunohistochemistry in archive gastrectomy specimens. Tumor angiogenesis was assessed by the microvessel density (MVD), which was determined by anti-CD34 immunostaining. Transient transfection of Kato III with cox-2 was associated with increased COX-2 expression, higher PGE2 production and upregulated VEGF expressions. Treatment with NS398, a specific COX-2 inhibitor, reduced VEGF expression in COX-2 expressing Kato III cells by 25%. Among the 67 gastric cancers examined, COX-2 overexpression was found in 45 (67%) cases whereas increased VEGF expression was detected in 46 (69%) cases. There was a significant association between COX-2 and VEGF expressions in gastric cancer (r=0.25, p=0.041). Additionally, tumor MVD was associated with both COX-2 (r=0.32, p=0.008) and VEGF (r=0.39, p=0.001) expressions. Our results showed that overexpression of COX-2 in both gastric cells and primary gastric cancer is associated with upregulation of VEGF and angiogenesis. Future studies should evaluate the potential anti-angiogenic effect of COX-2 inhibitors on human gastric cancer.     

COX-2、VEGF在NSCLC中的表达及与微血管生成的关系

目的探讨肺癌组织中COX-2、VEGF的表达及与血管生成和临床病理特征的关系。方法收集85例肺癌和20例肺良性病变标本,免疫组化S-P法检测COX-2、VEGF蛋白及MVD的表达并作相关分析。结果COX-2、VEGF、MVD在肺癌中的阳性表达率显著高于肺良性病变组织(P<0.05);COX-2表达与肺癌的组织学类型、分化程度和淋巴结转移相关(P<0.05);VEGF表达与肺癌分化程度和淋巴结转移相关(P<0.05);COX-2、VEGF、MVD呈两两正相关。结论COX-2、VEGF参与了肺癌的发生发展过程,COX-2可能通过上调VEGF促进肺癌的血管新生和发生发展。     

胃癌患者血清VEGF、COX-2表达的检测及临床意义

目的：检测胃癌患者血清中血管内皮生长因子（VEGF）、环氧合酶2（COX-2）的表达水平,探讨二者相关性及临床意义.方法：采用酶联免疫吸附试验（ELISA法）定量检测60例胃癌患者和30例健康人血清VEGF和COX-2水平.比较胃癌患者与健康人血清VEGF、COX-2浓度的差异.同时比较不同分期肿瘤患者血清VEGF、COX-2浓度的差异,并进行二者相关性分析.结果：胃癌患者血清VEGF水平（424.07±81.85pg/ml）明显高于健康人（117.23±20.09pg/ml） （P ＜0.01）.其水平与肿瘤大小、浸润深度、分化程度、有无转移、TNM分期有关（P＜0.05）.血清COX-2水平（41.43±9.52ng/ml）也明显高于健康人（16.88±6.27ng/ml）（P＜0.05）.其含量与胃癌分化程度、有无转移、TNM分期有关（P＜0.05）.二者的表达呈显著正相关（r=0.618,P＜0.01）.结论：胃癌患者血清中VEGF和COX-2高表达,其表达水平与肿瘤的分期相关,提示VEGF和COX-2在胃癌的发生和发展中发挥重要的作用.二者密切相关,在胃癌的诊断、治疗和预后评价中具有一定价值.     

CT增强时间密度曲线与肺癌血管生成关系的研究

背景与目的 新生血管形成与肿瘤细胞无限增殖密切相关.本研究的目的是分析肺癌组织中环氧化酶-2(COX-2)、血管内皮生长因子(VEGF)表达,微血管密度(MVD)与CT增强表现的相关性.方法 对经病理证实的25例肺癌及35例肺良性疾病患者行CT增强扫描,并应用PV法对病理标本进行免疫组化分析.结果 肺癌组COX-2(P＜0.05)、VEGF(P＜0.05)、MVD(P＜0.05)及CT强化峰值(P＜0.01)均明显高于肺良性肿瘤组.肺癌组织中COX-2、VEGF、MVD与组织学类型、临床分期、淋巴结转移及CT强化峰值之间有密切关系,与肺癌的分化程度无明显关系.结论 COX-2、VEGF、MVD可作为临床评价肿瘤发展、估计肿瘤预后的重要分子生物学指征.CT增强检查可以反映肺癌的血供特点,可根据CT增强峰值来推测肿瘤的侵袭、转移及预后情况.     

bFGF和celecoxib对胃癌BGC-823细胞株生长的影响及其机制

目的：探讨bFGF和celecoxib对人胃癌BGC-823细胞增殖及凋亡的作用及对COX-2、NF-κB、VEGF蛋白表达的影响.方法：bFGF和celecoxib作用于BGC-823人胃癌细胞后，MTT比色法测定细胞的增殖，使用流式细胞仪检测细胞凋亡率，荧光显微镜观察细胞凋亡形态，应用Western印迹分析法检测COX-2、NF-κB和VEGF蛋白的表达.结果：25ng/ml bFGF对BGC-823细胞有促增殖作用，能增强COX-2、NF-κB、VEGF蛋白表达，呈时间依赖性（P＜0.01）.不同浓度的celecoxib对BGC-823人胃癌细胞均有增殖抑制作用，并能促进细胞凋亡，使COX-2、NF-κB、VEGF蛋白表达明显减弱，呈浓度依赖性（P＜0.01）.结论：bFGF对BGC-823细胞具有促进增殖和COX-2、NF-κB、VEGF蛋白表达的作用.celecoxib对BGC-823细胞具有促进凋亡和抑制COX-2、NF-κB、VEGF蛋白表达的作用.COX-2、NF-κB、VEGF之间具有相关性（r分别为0.852、0.908、0.930，P＜0.01）.     

环氧化酶-2及其抑制剂与结直肠癌微血管和淋巴管生成的研究

目的 探讨环氧化酶-2(COX-2)在结直肠癌组织的表达与肿瘤生物学特征、微血管生成及淋巴管生成的关系及其抑制剂塞来昔布的抗肿瘤作用和机制.方法 应用免疫组化方法 检测64例结直肠癌组织中COX-2的表达、微血管形成及淋巴管生成,分析其相关性及与临床病理参数联系.临床晚期直肠癌患者7例,给予塞来昔布灌肠治疗15天,对活检肿瘤组织微血管及淋巴管进行对比.结果 COX-2的表达与结直肠癌的分期(P=0.003)和组织学类型(P=0.004)相关;COX-2高表达组微血管密度(MVD)和淋巴管密度(LVD)均高于COX-2低表达组(P<0.05).塞来昔布灌肠治疗后直肠癌微血管密度下降,淋巴管密度无差异.结论 COX-2可能通过促进淋巴管及微血管生成参与了结直肠癌的发生与发展.COX-2抑制剂塞来昔布可抑制直肠癌微血管生成.     

bFGFR、COX-2和MVD在胃癌中的表达及其与浸润转移的关系

目的 探讨碱性成纤维生长因子受体（bFGFR）、环氧合酶-2（COX-2）和微血管密度（MVD）与胃癌浸润、转移的关系。方法 选择80例手术切除的胃癌标本为观察组,40例慢性浅表性胃炎为对照组,应用免疫组织化学方法检测组织中bFGFR、COX-2和MVD的表达情况。结果 bFGFR及COX-2在胃癌患者中的阳性率为50.0%和52.5%。在对照组的阳性率分别为5.0%和0,差异均有统计学意义(P<0.01)。MVD在胃癌及对照组中的表达分别为（46.9±2.2）和（26.2±2.3）,差异有统计学意义（P<0.01）。三者的表达与肿瘤的浸润、淋巴及远处转移呈正相关(P<0.01或P<0.05),与肿瘤大小、分化程度无关(P>0.05)。bFGFR阳性和COX 2阳性组MVD值（48.7±10.2、49.6±11.6）均高于bFGFR阴性和COX-2阴性组（33.6±5.2、32.7±4.5,P<0.01）。bFGFR与COX-2的表达呈正相关（γ=0.700,P=0.0000）,二者在胃癌组织中的阳性表达强度与淋巴、远处转移呈正相关（P<0.01）。）结论 胃癌组织中bFGFR、COX-2和MVD的表达与胃癌的浸润、转移密切相关,三者在肿瘤血管形成中可能存在相互协同作用。三者的阳性表达可作为胃癌生长,转移的重要判定指标。     

环氧合酶-2对人SGC-7901胃癌细胞E-cadherin的表达及迁移能力的影响

目的 研究环氧合酶-2（COX-2）通过调控E-钙黏素（E-cadherin）对胃癌细胞侵袭迁移能力的影响。方法 分别应用塞来昔布（Celecoxib）及前列腺素E2(PGE2)对体外培养的人胃癌细胞SGC-7901进行干预,采用实时荧光定量反转录PCR检测COX-2、E-cadherin mRNA的表达;运用免疫荧光标记法结合激光共聚焦荧光显微镜分析E-cadherin的蛋白表达量;应用Transwell法检测细胞迁移能力的变化。结果 实时荧光定量反转录PCR检测塞来昔布明显抑制体外培养人胃癌细胞SGC-7901中COX-2 mRNA的表达（P＜0.01）,而E-cadherin mRNA的表达随着COX-2的表达下降而呈浓度与时间依赖性升高（P＜0.01）;运用PGE2干预后E-cadherin mRNA表达呈浓度与时间依赖性下降（P＜0.05或P＜0.01）。塞来昔布30 μmol/L干预人胃癌细胞SGC-7901 24、36、48 h后,激光共聚焦荧光显微镜检测E-cadherin的蛋白表达量明显升高（P＜0.05）;PGE2 1 μmol/L干预24、48 h后,E-cadherin蛋白表达量明显下降（P＜0.05）。塞来昔布组穿过Transwell小室的细胞数明显少于对照组（P＜0.01）,PGE2组穿过Transwell小室的细胞数明显高于对照组（P＜0.05）。结论 COX-2特异性抑制塞来昔布通过抑制COX-2的表达,上调E-cadherin表达量,抑制体外培养人胃癌细胞SGC-7901的迁移能力;外源性PGE2能够下调SGC-7901胃癌细胞E-cadherin表达量从而促进肿瘤细胞的迁移能力。     

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.     

胃癌组织EGFR和VEGF的表达及其意义

目的探讨胃癌组织EGFR和VEGF的表达及其与临床病理特征的关系。方法应用免疫组化方法检测正常胃黏膜和胃癌切除标本EGFR和VEGF的表达,并与临床病理参数进行比较分析。结果胃癌组织EGFR和VEGF阳性表达率分别为64.7%和58.8%;正常胃黏膜组织EGFR和VEGF阳性表达率分别为0%和10.0%,差异有统计学意义（P=0.000）;EGFR阳性表达与肿瘤分化程度、浸润深度、淋巴结转移、远处转移及临床TNM分期呈显著相关,VEGF阳性表达与肿瘤分化程度、浸润深度、淋巴结转移、远处转移、脉管内癌栓和临床TNM分期呈显著相关（P〈0.01和P〈0.05）。EGFR表达阳性者有69.7%同时伴有VEGF表达阳性,EGFR和VEGF双阳性表达者的根治切除率仅为30.4%,明显低于阴性表达者（P=0.000）。结论胃癌组织EGFR和VEGF表达上调与肿瘤分化程度、浸润深度、淋巴结转移、远处转移、脉管内癌栓和TNM分期有关,EGFR促进肿瘤血管生长可能通过上调VEGF表达,胃癌组织EGFR和VEGF表达可能成为从同期别病例中甄别靶向治疗获益病例的主要预后指标。     

COX-2 iNOS及VEGF在胃不典型增生胃癌中的表达及其意义

目的:探讨COX-2、iNOS及VEGF在胃不典型增生及胃癌中的表达、相互关系及在胃癌中的作用.方法:采用免疫组化Power visionTM两步法对84例胃癌和54例胃不典型增生组织中COX-2、iNOS及VEGF的表达进行检测.结果:COX-2、iNOS及VECF在胃癌中表达的阳性率分别为66.67%、77.38%、61.90%,均高于胃不典型增生组织(P＜0.05).COX-2、iNOS及VEGF表达与肿瘤的大小、淋巴结转移呈正相关,COX-2、VEGF表达与肿瘤浸润深度呈正相关,VEGF与COX-2、iNOS的表达呈正相关(P＜0.05).结论:COX-2、iNOS及VEGF与胃癌的发生、浸润转移相关,COX-2、iNOS通过增强VEGF的表达而促进肿瘤血管生成及转移.     

CD105 、COX-2 和VEGF 在结直肠癌中的表达及其与血管新生的关系

 目的 探讨结直肠癌中CD105在新生血管中的表达，环氧化酶（COX-2）和血管内皮生长因子（VEGF）表达及其与血管生成的关系。方法 应用免疫组化SP法检测58例结直肠癌CD105表达的微血管密度，以及COX-2、VEGF的表达。结果 58例结直肠癌中，CD105表达的MVD值为（36．50±9．59），COX-2和VEGF的阳性表达率各为69％和67．2％。COX-2或VEGF表达阳性组的MVD值显著高于COX-2或VEGF表达阴性组（P〈0．05）。COX-2和VEGF均阳性组的MVD值显著高于均阴性组（P〈0．01）。COX-2与VEGF表达显著正相关；COX-2、VEGF表达均与MVD显著正相关（P〈0．01）。结论 CD105是结直肠癌新生血管的特异性标记物，COX-2表达与结直肠癌血管生成有关，VEGF可能是COX-2诱导血管生成的重要介质。     

Expression of cyclooxygenase-2 and matrix metalloproteinase-9 in gastric carcinoma and its correlation with angiogenesis

OBJECTIVE: To investigate the expression of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 in gastric carcinomas, and to correlate this expression with clinicopathological parameters and angiogenesis. METHODS: Ninety-six resected tumor specimens from patients with gastric carcinoma were obtained, and 30 corresponding paracancerous normal tissues were randomly selected as a control. Immunohistochemical staining was used for detecting the expression of COX-2 and MMP-9. Monoclonal antibody against CD34 was used for displaying vascular endothelial cells, and microvascular density (MVD) was calculated by counting of CD34-positive vascular endothelial cells. RESULTS: The positive expression rates of COX-2, MMP-9 and MVD in the cancerous tissue were 80.2%, 74.0%, and 32.5 +/- 8.3, respectively, which were significantly higher than those in the normal tissue (P < 0.01). COX-2, MMP-9 expression rates and MVD in the patients with stages III and IV were 91.4%, 84.5% and 34.9 +/- 8.7, respectively, which were significantly higher than those in the patients with stages I and II (P < 0.01). In addition, the Spearman rank correlation test showed that tumor MVD was closely associated with COX-2 (r = 0.311, P < 0.01) and MMP-9 (r = 0.349, P < 0.01) expressions. CONCLUSIONS: Overexpression of COX-2 and MMP-9 is related to tumor invasion and lymph node metastasis in the gastric carcinoma. These results provide evidence that COX-2 contribute to gastric cancer development by promoting MMP-9 expression and angiogenesis.