TFPI-2与VEGF在胰腺癌中的表达

目的探讨胰腺癌中TFPI-2表达对胰腺癌肿瘤血管生成的影响.方法采用免疫组织化学方法检测41例胰腺癌组织中TFPI-2、VEGF的表达及CD34单克隆抗体标记的微血管密度(MVD).结果Ⅰ、Ⅱ期胰腺癌及无远处转移的胰腺癌组织中TFPI-2阳性表达率分别为65.4%和57.1%,Ⅲ、Ⅳ期及有远处转移的胰腺癌组织中的TFPI-2阳性表达率分别为13.3%和23.1%,TFPI-2表达率,Ⅰ、Ⅱ期高于Ⅲ、Ⅳ期,无远处转移高于有远处转移,差异有统计学意义(P＜0.05);VEGF阳性表达率在Ⅰ、Ⅱ期及无远处转移的胰腺癌组织分别为23.0%和32.1%,在Ⅲ、Ⅳ期及有远处转移的胰腺癌组织分别为66.7%和61.5%,两者比较,差异有统计学意义(P＜0.05);Ⅲ、Ⅳ期及有远处转移的胰腺癌组织MVD值分别为28.47±2.23和19.00±2.58,高于Ⅰ、Ⅱ期的26.92±1.06及无远处转移的16.68±1.79,差异有统计学意义(P＜0.05);胰腺癌组织中的TFPI-2的表达与VEGF的表达呈负相关(r=-0.54),差异有统计学意义(P＜0.05);MVD与TFPI-2表达有关,TFPI-2阳性表达的胰腺癌组织MVD值为33.33±3.23,低于TFPI-2阴性表达的胰腺癌组织36.00±3.17,两者比较,差异有统计学意义(P＜0.05).结论胰腺癌中TFPI-2可能通过下调VEGF的表达抑制肿瘤新生血管的形成,从而抑制胰腺癌的生长、转移.     

视网膜新生血管性疾病与血管生长促进因子

视网膜新生血管性疾病是世界范围最严重致盲性眼病之一，其发病机制尚未明了，但近年来生长因子在视网膜新生血管形成中的作用已形成共识。本文就与视网膜新生血管相关的血管生长促进因子作一综述。     

食管鳞状细胞癌抑制蛋白-1的表达与血管生成的关系

目的 通过观察DNA结合抑制蛋白-1(ID-1)在食管鳞状细胞癌(ESCC)中的表达及其与微血管密度(MVD)的关系,探讨ID-1在ESCC发生、发展及血管生成中的作用.方法 应用SP法对102份ESCC组织、30份切缘正常组织进行ID-1和CD34免疫组织化学染色,检测癌组织、正常食管黏膜组织中ID-1的表达和MVD值,并分析ID-1的表达与ESCC临床病理特征及MVD之间的关系.结果 ESCC组织中ID-1的表达显著高于切缘正常组织(P＜0.01),ID-1的表达与MVD呈正相关(P＜0.01),在ID-1高表达组中病例MVD值高于ID-1低表达组(P＜0.01),ID-1表达与患者的年龄、性别、浸润深度及是否伴淋巴结转移均无明显相关.结论 ID-1可能在ESCC的发生、血管生成和侵袭转移中起重要作用,可能是ESCC的重要促血管生成因子之一.     

小鼠视网膜新生血管模型的简易制备

目的:采用简便易行的方法制备小鼠视网膜新生血管动物模型。方法:新生小鼠20只随机分为两组,实验组于出生后第7~12 d置于75%氧箱内饲养,对照组于正常环境饲养。至第17 d时处死小鼠,摘取眼球,固定切片,行苏木精-伊红(H-E)染色,计数突破视网膜内界膜的内皮细胞核数,免疫组化法观察视网膜各层血管内皮生长因子(VEGF)的表达。结果:实验组平均每个切面突破视网膜内界膜的内皮细胞核数为(25.70±4.90)个,对照组平均为(0.85±1.02)个,两者比较差异有显著性意义(P<0.01);对照组VEGF染色较实验组减弱。结论:该方法能建立稳定的视网膜新生血管动物模型。     

氩激光诱导色素兔脉络膜新生血管的实验研究

目的:研究氩激光诱导色素兔脉络膜新生血管(CNV)的实验条件。方法:分别对3组动物实验眼用不同功率(0.4,0.8,1W)的氩激光光凝视网膜,光凝后3,7,14,28,56及91d行光学相干断层扫描(opticalcoherencetomography,OCT)、荧光素眼底血管造影(fundusfluoresceinangiography,FFA)和吲哚菁绿血管造影(indocyaninegreenangiography,ICGA)后处死动物,取光凝区眼球壁制作标本,进行光镜和透射电镜观察。结果:第1组未见CNV生长,第2,3组光凝后7d出现CNV,28d达高峰,56d后开始减少。结论:高功率(0.8～1W)的氩激光能有效诱导色素兔CNV,是较好的动物模型。     

Cyclooxygenase-2 promotes angiogenesis by increasing vascular endothelial growth factor and predicts prognosis in gallbladder carcinoma

AIM: To investigate the relationships between the expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and the degree of vascularization, clinicopathologic feature, survival time of patients with gallbladder carcinomas. METHODS: Sixty-four gallbladder carcinoma specimens were evaluated for COX-2, VEGF expression by immunohi stochemical methods. Microvessel counts (MVC) were determined using CD34. The relationships between COX-2, VEGF expression, CD34-stained MVC, clinicopathologic features and survival time were analyzed. The correlations between COX-2 and VEGF expression, CD34-stained MVC were also investigated. RESULTS: COX-2, VEGF immunoreactivity were observed in 71.9% (46/64) and 54.7% (35/64) specimens, respectively. The average MVC in 64 cases of gallbladder carcinoma was 57±14 per high power vision field. The status of MVC was closely correlated with Nevin staging, tumor differentiation and lymph node metastasis (P<0.01, 0.002, and 0.003, 0.000, respectively). Increased VEGF expression was significantly correlated with tumor differentiation (poorly and moderately>well differentiated, P<0.05, P = 0.016). Clinical stages had no relation with the expression of VEGF (P>0.05, P = 0.612). There was a positive correlation between COX-2 expression and clinical stages. The positive rate of COX-2 was higher in cases of Nevin stages S4-S5 (81.8%) than in those of Nevin stages S1-S3 (50.0%) with a statistical significance (P0.01, P = 0.009). The expression of COX-2 did not vary with differentiation (P>0.05, P= 0.067). Statistically significant differences were also observed according to lymph node metastasis, COX-2 expression and VEGF expression (P<0.01,0.000, and 0.001, respectively). There was no relation between VEGF, COX-2 expression, MVC and the age and sex of patients. MVC and VEGF positive rate in the COX-2 positive gallbladder carcinoma tissue was higher than that in the COX-2 negative tissue (P<0.05, 0.000, and 0.032, respectively). Patients with VEGF, COX-2 positive tumors had a significantly shorter survival time than those with negative tumors (P<0.05,0.004, 0.01, respectively). CONCLUSION: Augmented tumor neovascularization induced by VEGF may be one of the several effects of COX-2 responsible for poor prognosis of human gallbladder carcinoma. COX-2 inhibitor, either in combination therapy with other agents, or for chemoprevention, may be effective via suppression of angiogenesis in this fatal disease.     

Intravitreal triamcinolone does not alter basal vascular endothelial growth factor mRNA expression in rat retina

Intravitreal triamcinolone inhibits choroidal neovascularization. To investigate if vascular endothelial growth factor (VEGF) is affected, we examined VEGF expression after intravitreal triamcinolone administration in rat retina. Using in situ hybridization, we have found dense clustered VEGF mRNA signals in the retinal pigment epithelium, moderate patchy signals in the inner nuclear layer, and positive labeling in a sub-population of ganglion cells. Densitometry and northern blot analysis revealed no significant alteration of VEGF mRNA expression pattern and level 3-21 days after triamcinolone injection. Our data indicate that intravitreal triamcinolone does not affect basal VEGF mRNA expression in normal adult rat retina.     

环氧合酶2反义寡核苷酸对胰腺癌新生血管生成的抑制作用

目的 研究环氧合酶-2反义寡核苷酸（COX-2 AS-ODN）对胰腺癌新生血管生成的抑制作用,探讨前列腺素E2（PGE2）在胰腺癌新生血管生成中的调节作用。方法 设计、合成特异性靶向COX-2 AS-ODN。人胰腺癌PC-3细胞进行体外培养,转染COX-2 AS-ODN后0、12、24、40和72h以荧光显微镜观察细胞情况。第二批PC-3细胞用于研究量-效关系,分为5组：对照组、Lipo组（接种Lopofectin脂质体）、C1组（1μg COX-2 AS-ODN Lipo/孔）。第三批PC-3细胞用于研究时-效关系,接种3μg COX-2 AS-ODN Lipo/孔后观察0、12、24、48和72h。用RT-PCR观察COX-2 mRNA的表达。以Western印迹观察分别加入3μg和9μg COX-2 AS-ODN/瓶后PC-3细胞COX-2蛋白质的表达。18只鸡胚分3组,其绒毛尿囊（CAM）分别接种PC-3细胞以及Lipo、Lipo COX-2 AS-ODN、Lipo COX-2 AS-ODN 前列腺素E2（PGE2）,另6只鸡胚仅接种PC3细胞用作对照。用Leica体视显微镜观察新生血管生成情况。结果 RT-PCR示随转染COX-2 AS-ODN浓度的增加,PC3细胞的COX-2 mRNA表达逐渐下调（直到COX-2 AS-ODN浓度为0.2μmol/L时）。COX-2 AS-ODN的作用于12h后最强,以后渐弱,48h后基本消失。Western印迹表明COX-2 AS-ODN转染组的COX-2蛋白质表达受抑制,9μg COX-2 AS-ODN/瓶组的抑制强于3μg COX-2 AS-ODN/瓶组。Lipo COX-2 AS-ODN组鸡胚CAM移植肿瘤中的新生血管生成密度明显低于Lipo组;Lipo COX-2 AS-ODN PGE2组的新生血管密度介于以上两组之间。结论 COX-2 AS-ODN显著抑制胰腺癌新生血管的生成。内源性COX-2参与对胰腺癌新生血管生成的调节,PGE2在该过程中起重要的介导作用。     

Monocyte chemotactic protein 1 increases homing of mesenchymal stem cell to injured myocardium and neovascularization following myocardial infarction

Objective：To investigate the effect of MCP-1 on mesenchymal stem cells（MSCs） homing to injured myocardium in a rat myocardial infarction（MI） model. Methods：Rat myocardial infarction model was established by permanent left anterior descending branch ligation. Mesenchymal stem cells from donor rats were cultured in IMDM and labeled with BrdU. The Rats were divided into two groups. Monocyte chemotactic protein I（MCP-1） expression were measured by in situ hybridization and immunohistochemistry in the sham operated or infarcted hearts at 1, 2, 4, 7, 14 and 28 days post operation in MCP-1 detection group. The rats were injected with MCP-1, anti-MCP-1 antibody or saline 4 days after myocardial infarction in intervention group. Then, a total of 5 × 10^6 cells in 2.5 ml of PBS were injected through the tail vein. The number of the labeled MSCs in the infarcted hearts was counted 3 days post injection. Cardiac function and blood vessel density were assessed 28 days post injection. Results：Self-generating MCP-1 expression was increased at the first day, peaked at the 7^th day and decreased thereafter post MI and remained unchanged in sham operated hearts. The MSCs enrichment in the host hearts were more abundant in the MI groups than that in the non-MI group（P= 0.000）, the MSCs enrichment in the host hearts were more abundant in the MCP-1 injected group than that in the anti-MCP-1 antibody and saline injected groups （P = 0.000）. Cardiac function was improved more in MCP-1 injected group than anti-MCP-1 antibody and saline injected groups（P= 0.000）. Neovascularization in MCP-1 injected group significantly increased compared with that of other groups（P = 0.000）. Conclusion： Myocardial MCP-1 expression was increased only in the early phase post MI. MCP-1 may enhance MSCs homing to the injured heart and improve cardiac function by promoting neovascularization.     

血管内皮生长因子在非小细胞肺癌中的表达及其意义

探讨血管内皮生长因子在肺癌中的表达及与肿瘤生长转移,预后和新生血管形成的关系。方法对５３例周围型非小细胞肺癌患者,采用免疫组织化学法,进行ＶＥＧＦ抗体标记和肿瘤组织ＶＥＧＦ表达;用Ｆ８因子抗体标记瘤组织的血管生成。