血管生成素在人脑胶质瘤中的表达及其临床意义

目的　研究血管生成素 (Ang)家族中Ang 1、Ang 2蛋白在人脑胶质瘤组织中的表达水平 ,探讨其与脑胶质瘤临床病理特征的关系。方法　采用免疫组化方法 ,检测 42例人脑胶质瘤组织中Ang 1和Ang 2蛋白的表达。 结果　Ang 1、Ang 2蛋白在胶质瘤细胞和血管内皮细胞中均有表达。Ang 1的表达水平与患者临床病理特征无明显相关性 (P >0 .0 5 )。Ang 2蛋白表达水平与胶质瘤的临床病理分级、瘤周脑水肿程度显著相关 (P <0 .0 1) ,而与患者性别、年龄、肿瘤大小无关。结论　Ang 2过表达与临床病理分级和瘤周脑水肿密切相关 ,可能成为判断胶质瘤恶性进展和预后的重要指标     

胶质瘤促血管生成素2基因表达的临床意义（附52例分析）

目的　探讨胶质瘤促血管生成素2 (Ang2) 基因在脑胶质瘤的表达及其临床意义。方法　采用逆转录聚合酶链反应(RT PCR) 和链酶亲和素过氧化物酶复合物SABC法检测52例人脑胶质瘤和8例正常脑组织中Ang2基因表达。结果　50 例脑胶质瘤和8 例正常脑组织均可表达Ang2 mRNA片段。高恶度胶质瘤Ang2 mRNA及蛋白表达显著高于低恶度胶质瘤(P<0 01); 低恶度胶质瘤Ang2 mRNA及蛋白表达显著高于正常脑组织(P<0 05)。免疫组化染色显示, Ang2蛋白主要分布在高恶度胶质瘤组织的瘤细胞和内皮细胞, 低恶度胶质瘤呈低水平表达, 正常脑组织不表达。结论　Ang2的表达与胶质瘤的分级密切相关, 可能对胶质瘤的恶性演进起促进作用。     

结直肠肿瘤中血管生成素的表达及其与微血管密度的关系

目的:探讨结直肠肿瘤中血管生成素(ang iopo ietin,A ng)的表达及其与微血管密度(m icrovessel density,MVD)的关系。方法:采用免疫组化法,检测91例结直肠腺癌、20例结直肠腺瘤、24例正常结直肠组织中A ng-1和A ng-2的蛋白表达,以F-Ⅷ单克隆抗体标记血管内皮细胞,并计数MVD。结果:A ng-1在正常组织(7.07±2.00)的表达明显高于结直肠腺瘤(1.75±1.98)和腺癌(1.40±1.22),P<0.01;结直肠腺癌的A ng-2阳性表达率高于结直肠腺瘤、正常组织(P<0.01)。A ng-2的表达与结直肠腺癌的分化程度、有无脉管侵犯密切相关;在135例组织中,A ng-1表达与A ng-2表达(r=-0.338,P<0.01)、A ng-1表达与MVD(r=-0.388,P<0.01)、A ng-2表达与MVD(r=0.594,P<0.01)均有相关性。结论:A ng-2在结直肠腺癌中的过度表达对血管新生起重要作用,可能是评估结直肠腺癌恶性程度和预后的可靠指标。     

Targeting angiogenesis in ovarian cancer

Results of standard chemotherapy in ovarian cancer are hampered by the development of drug resistance leading to disease recurrence. This prompted interest in the development of therapies targeting critical pathways responsible for tumor progression. Angiogenesis is a key process that enables ovarian cancer growth and metastasis in the peritoneal space. Its regulation relies on signaling mechanisms initiated by the vascular endothelial growth factor, the platelet-derived growth factor, the fibroblast growth factor, angiopoietins, and others. These pathways are not only important to the modulation of the tumor microenvironment and vasculature, but also control cancer cell proliferation and survival. In this review, we discuss preclinical evidence supporting the rationale for inhibiting these pathways and provide an overview for the clinical development of agents targeting them. Clinical trials evaluating such agents alone and in combination with chemotherapy are ongoing. Early clinical results position antiangiogenic therapy at the forefront of change to the standard treatment of difficult to treat ovarian cancer.     

The Tie2 Receptor Antagonist Angiopoietin-2 in Systemic Lupus Erythematosus: Its Correlation with Various Disease Activity Parameters

Background: Systemic lupus erythematosus is one of the autoimmune diseases characterized by multisystem involvement associated with autoantibody and immune complex vasculitis along with endothelial cell damage. Objective: to study the possible role of Angiopoietin- 2 (Ang-2) as a recently highlighted inflammatory and angiogenic mediator in the pathogenesis of SLE and its correlation with the state of another inflammatory marker, P-Selectin, as well as with various markers of the disease activity. Patients and methods: The present study included 3 main groups: active SLE patients (group I), inactive SLE patients (group II) and healthy normal control subjects (group III). Groups I and II were subjected to disease activity assessment using the SLEDAI scoring system and measurement of plasma Ang-2 and P-Selectin by ELISA in addition to various laboratory investigations to assess disease activity as: Complete blood count, ESR, serum creatinine, C3, C4 and 24-h urinary proteins. Results: The mean level of Plasma Ang-2 and P-selectin showed a high significant increase in active group compared to inactive SLE patients and control subjects (p < 0.001).There was a significant positive correlation between Ang-2, P-Selectin, and each of SLEDAI score and 24-h urinary proteins in all SLE patients as well as in the active group, and Ang-2 was a significant independent marker for proteinuria. A significant negative correlation was found between Ang-2, P-Selectin and each of C3, C4. Ang-2 and P-Selectin showed a high sensitivity and specificity in the patients with SLE. Conclusion: Our study suggests that Ang-2 may be a more useful marker than P-Selectin, C3 and C4 in the assessment of disease activity.     

血管生成素样蛋白1和2水平在急性心肌梗死患者中的表达及临床意义

目的 探讨血管生成素样蛋白1（Ang-1）和血管生成素样蛋白2（Ang-2水平）在急性心肌梗死（AMI）患者中的表达以及与肌钙蛋白T（cTnT）的相关性.方法 选取AMI患者75例,同期选择健康体检者50例为对照组,采用酶联免疫吸附试验（ELISA）和化学发光法分别检测研究对象中Ang-1、Ang-2和cTnT水平,并与对照组作比较.结果 AMI患者Ang-2、Ang-2/Ang-1水平分别为（2310.2±131.6） ng/L和（11.9±1.3）,显著高于对照组的（905.8±171.4） ng/L和（4.6±1.8）,差异有统计学意义（P＜ 0.05）;AMI患者Ang-1水平为（19 589.3±2033.4） ng/L,对照组为（19 612.1±1824.1） ng/L,差异无统计学意义（P＞0.05）.Ang-2水平和Ang-2/Ang-1与cTnT均呈正相关（r=0.597,0.604,P＜0.05）.结论 高Ang-2水平和Ang-2/Ang-1是心肌梗死的危险因素,并与cTnT正相关.     

Expression and significance of Tie-1 and Tie-2 receptors, and angiopoietins-1, 2 and 4 in colorectal adenocarcinoma： Immunohistochemical analysis and correlation with clinicopathological factors

AIM: There is strong evidence that tyrosine kinases are involved in the regulation of tumor progression, cellular growth and differentiation. Recently, many kinds of tyrosine kinase receptors have been reported, among them Tie-1 and Tie-2 receptors constitute a major class. Angiopoietin (Ang)-1 is known as a ligand of Tie-2 tyrosine kinase receptor. The objective of this study was to establish a comprehensive Tie-1 and Tie-2 and Ang-1, 2 and 4 expression profile in human colorectal adenocarcinomas. METHODS: We examined 96 cases of surgically resected human colorectal adenocarcinoma by immunohistochemistry and investigated the statistical correlation between the expressions of Ties and Angs and clinicopathological factors. RESULTS: Among the 96 cases of adenocarcinoma, 87 (90.6%), 92 (95.8%), 83 (86.5%), 89 (92.7%), and 76 cases (79.2%) showed positive staining in the cytoplasm of carcinoma cells for the Tie-1 and Tie-2 and Ang-1, 2 and 4 proteins, respectively. Histologically, the expressions of Ties and Angs were variable. The expressions of Ties and Angs were correlated with several clinicopathological factors, but did not correlate with the presence of lymph node metastasis. Ties and Angs were highly expressed in human colorectal adenocarcinoma cells. CONCLUSION: These findings suggest that the Tie-Ang receptor-ligand complex is one of the factors involved in the cellular differentiation and progression of human colorectal adenocarcinoma.     

人血管生成素1真核表达载体的构建及在兔骨髓间充质干细胞的表达

目的 探索构建人血管生成素1(human angiopoietin 1，hAng-1)真核表达载体，转染体外培养兔骨髓间充质干细胞(marrow mesenchymal stemcells，MSCs)修复骨缺损的可能性。方法 基因重组和限制性内切酶酶切构建真核表达载体pcDNA3-hAng 1，经脂质体DOTAP介导质粒转染兔MSCs，G418筛选阳性克隆，RTPCR及免疫印迹杂交检测hAng-1 mRNA及蛋白表达。结果 重组真核表达载体pcDNA3-hAng-1经限制性内切酶Xho-I和BamH-I酶切后，电泳显示1．4kb hAng-1目的片段和5．4kb pcDNA3载体片段，转染兔MSCs后，RT-PCR检测出目的基因mRNA，免疫印迹杂交检出hAng-1的蛋白表达。结论 构建的真核表达载体pcDNA3-hAng-1能在转染的兔MSCs中表达，可以为组织工程骨修复奠定基础。     

血管生成素1在大鼠急性射线皮肤损伤创面愈合过程中的表达

目的研究大鼠急性射线皮肤损伤创面愈合过程中血管生成素1（Ang-1）的表达情况。方法将雄性SD清洁级大鼠54只分为3组。照射组（=24）,直线加速器产生射线（45 Gy）单次照射大鼠臀部皮肤40 mm×40 mm,建立急性射线皮肤损伤模型;烧伤组（=24）,将直径30 mm铜柱于100℃沸水中放置15min,取出后在无外界压力下置于大鼠臀部皮肤8 s,建立深Ⅱ°热力烧伤模型;对照组（=6）,无特殊处理。取不同时期创面皮肤组织,采用免疫组织化学（SP法）检测不同时相点各组大鼠创面组织中Ang-1的表达。结果免疫组化显示,烧伤组在伤后1、2及3周Ang-1表达积分吸光度值均要大于照射组,差异均有统计学意义（〈0.05）。结论急性射线皮肤损伤创面愈合过程中Ang-1持续低表达,不能形成峰值,可能是其损伤创面难愈合的机制之一。     

The changing face of sympathetic overactivity in hypertension

Background. The precise pathophysiological processes underlying the prothrombotic or hypercoagulable state in atrial fibrillation (AF) remain uncertain. We hypothesized a relationship between abnormal endothelial damage/dysfunction, coagulation, and angiogenic factors, thereby contributing to increased thrombogenicity.

Methods. Plasma levels of von Willebrand factor (vWF, an index of endothelial damage/dysfunction) and tissue factor (TF, an index of coagulation), as well as the angiogenic factors, vascular endothelial growth factor (VEGF), angiopoietin‐1 (Ang‐1) and angiopoietin‐2 (Ang‐2), were measured by enzyme‐linked immunosorbant assay (ELISA) in 59 chronic AF patients. Data were compared to 40 age‐ and sex‐matched healthy controls in sinus rhythm.

Results. Plasma vWF, VEGF and Ang‐2 were significantly higher in AF patients compared to healthy controls (P = 0.005, P = 0.0055 and P<0.0001 respectively) but there were no significant differences in plasma Ang‐1 or TF levels between the two groups (P = 0.925 and P = 0.121 respectively). Significant correlations were found between VEGF and vWF levels (Spearman, r = 0.262, P = 0.011) and between VEGF and Ang‐2 (r = 0.333, P = 0.001).

Conclusions. Raised VEGF in association with Ang‐2 and vWF may reflect a link between abnormal endothelial damage/dysfunction and angiogenic factors. These may act together to alter TF expression and endothelial integrity, thereby contributing to the prothrombotic state in AF.