血管内皮生长因子及其受体在抗肿瘤治疗应用的研究进展

肿瘤的生长依赖肿瘤新生血管的形成。血管内皮生长因子（VEGF）是一类能促进血管生成的细胞因子，能诱导细胞的有丝分裂和调节内皮细胞的通透性。VEGF及其受体介导的肿瘤血管新生在肿瘤的生长和转移中具有重要的作用。本文综述了VEGF及其受体的分类、作用机制及在抗肿瘤治疗中的应用。     

Bcl-2在肺癌中的表达及其与VEGF和血管新生关系的研究

目的探讨63例人肺癌中Bcl-2蛋白的表达与VEGF和血管新生的关系。方法采用免疫组织化学方法,以抗CD34单抗标记血管内皮细胞以测定血管新生,抗Bcl-2单抗标记Bcl-2蛋白,抗VEGF165单克隆抗体检测VEGF的表达。结果所有肺癌组织均有不同程度血管新生,iMVD4～138.7(44.5±29)/×400,Bcl-2蛋白表达率44.4%(28/63),VEGF的表达率50.8%(32/63)。Bcl-2表达在Ⅰ、Ⅱ期(55.3%)明显高于Ⅲ、Ⅳ期(28%)(P<0.05),而与组织类型无关;VEGF与组织类型、临床分期、患者性别、年龄等临床参数无关;所有肺癌组织中Bcl-2蛋白表达与VEGF和血管新生未见明显相关。结论Bcl-2蛋白表达与VEGF和血管新生未见相关;人肺癌的发生发展Bcl-2蛋白过度表达有关;Bcl-2蛋白表达可能为肺癌早期事件,可作为评定预后的生物学指标。     

VEGF受体酪氨酸激酶抑制剂的研究进展

肿瘤的生长和侵袭、转移依赖于新生血管的形成.抑制肿瘤介导的血管生成,阻断癌细胞的营养途径,就可有效抑制癌细胞增殖.血管内皮生长因子(VEGF)是肿瘤新生血管形成中的关键性促血管生长因子,它与特异性高表达在新生血管内皮细胞表面的受体酪氨酸激酶结合,激活酪氨酸激酶从而发挥生物学功能.因而以VEGF受体酪氨酸激酶为靶点的肿瘤血管靶向性治疗已成为近几年肿瘤治疗的新途径[1-3].     

舌癌组织中P53和血管内皮生长因子的表达及其与肿瘤血管形成的关系

<正>新生血管形成是肿瘤生长和转移的基础,血管内皮生长因子(VEGF)能刺激血管内皮细胞增殖,对肿瘤血管形成有重要作用。Mukhopadhyay等[1]和Fontanini等[2]认为,p53基因突变可通过调控VEGF的表达水平来影响肿瘤血管的形成。为了解突变型P53、VEGF和肿瘤内微血管密度     

角膜新生血管形成中血管内皮生长因子的表达

为探讨角膜新生血管形成中血管内皮生长因子（VEGF）的表达，建立家兔角膜碱烧模型后3天，7天、11天，14天处死动物，分别观察与测量新生血管数量与长度，VEGF表达，微血管数量，结果表明，角膜碱烧伤后不同时间内，VEGF蛋白染色强度与宏观观察新生儿血管长度及镜下测量微血管数量是同表变化；VEGF表达与新生血管发生位置一致，结论：VEGF是一种重要的新生血管形成因子，其表达与新生血管形成有密切关系。     

Bevacizumab在肿瘤治疗中的现状

<正>新生血管的形成是肿瘤增殖、侵袭和转移的必要条件,在影响它的诸多因子中血管内皮生长因子 (VEGF)是最重要的因素之一。VEGF家族成员主要包括VEGFA、VEGFB、VEGFC、VEGFD、VEG-     

双氯酚酸钠抑制VEGF对角膜新生血管调控作用的研究

目的探讨双氯酚酸钠抑制血管内皮生长因子(VEGF)对调控角膜新生血管的作用。方法建立化学伤后大鼠角膜新生血管动物模型,随机分为双氯酚酸钠组和生理盐水组。计算两组各个阶段新生血管面积,免疫组织化学染色方法检测VEGF蛋白在角膜各层中的分布,测定积分光密度确定表达的蛋白量。结果正常SD大鼠角膜中表达极低的VEGF蛋白;各个时段实验组的血管生长速度和面积均小于对照组(P<0.05);各个时段实验组VEGF表达少于对照组(P<0.01),均具有显著差异;各组内VEGF表达和角膜新生血管生成具有显著正相关(P<0.05)。结论双氯酚酸钠可以抑制碱烧伤后角膜VEGF的表达,从而可以调控角膜修复和炎症性新生血管生成过程。     

血管形成以及VEGF-Nrp 1 信号通路调控皮肤肿瘤干细胞的形成

肿瘤的发生、转移与组织内血管形成有着极其密切的关联。通过不同途径阻断血管内皮细胞生长因子（VEGF）及其受体的结合,达到抑制肿瘤组织中新生血管形成,并发挥治疗肿瘤的作用是公认的治疗模式。近期的研究发现,皮肤鳞状细胞癌组织中存在一定数量的肿瘤干细胞,VEGF在靠近血管的肿瘤干细胞中高表达。     

血管内皮细胞生长因子与抗肿瘤转移治疗的研究

血管内皮细胞生长因子(VEGF)是最重要的刺激血管新生的细胞因子。VEGF的生物学效应是通过其特异性的膜受体即VEGF受体介导实现的。本文就VEGF及其受体的基因和蛋白结构、生物学作用、信号转导通路及在抗肿瘤血管新生治疗方面的研究进展作一综述。     

鼻咽癌患者放疗前后测定血清VEGF的临床意义

众多的研究证实，实体肿瘤的生长依赖新生血管的形成。新生血管即为肿瘤细胞的生长、增殖提供营养供应及代谢产物排除途径，也促进肿瘤细胞的恶性演变，对肿瘤局部生物学行为起重要影响。研究表明，VEGF对内皮细胞的增生有强烈的刺激作用，     

临床实习护士学生就业压力源的调查

目的了解实习护士学生就业压力源因素。方法利用自编的实习护士学生就业压力源调查问卷对67位临床实习护士学生进行调查。结果实习护士学生就业压力源以学校因素最高,其次依次为社会环境因素、家庭因素、专业因素、个人因素。学生学历除了在压力源中社会环境因素有差异外,其余各因素均无差异。父母职业是否与医疗卫生事业相关在压力源因素中除了学校因素没有差异外,在其余四个因素都有差异,是否独生子女在压力源中个人因素和家庭因素有差异,其余因素都无差异。结论临床实习护士学生就业压力与社会环境因素、家庭因素、专业因素、个人因素均有相关,临床教学老师应该了解学生就业压力源因素,帮助学生解除心理压力,明确就业方向。     

Factor analysis shows that female rat behaviour is characterized primarily by activity, male rats are driven by sex and anxiety

This experiment explored sex differences in behaviour using factor analysis to describe the relationship between different behavioral variables. A principal component solution with an orthogonal rotation of the factor matrix was used, ensuring that the extracted factors are independent of one another, and thus reflect separate processes. In the elevated plus-maze test of anxiety, in male rats factor 1 accounted for 75% of the variance and reflected anxiety, factor 2 represented activity, and accounted for 24% of the variance. This contrasted with the finding in female rats in which factor 1 was activity, accounting for 57% of the variance, with the anxiety factor accounting for only 34% of the variance. When behaviour in both the plus-maze and holeboard were analysed, a similar sex difference was found with anxiety emerging as factor 1 in males and holeboard activity as factor 1 in females. Locomotor activity in the inner portion of the holeboard loaded on the anxiety factor for males, but on activity for females. When behaviours in the plus-maze and sexual orientation tests were analysed, anxiety emerged as factor 1 in males, sexual preferences factor 2, and activity factor 3. In females, activity was factor 1, sexual preference factor 2, anxiety factor 3, and social interest factor 4. These results suggest caution should be exercised in interpreting the results from female rats in tests validated on males because the primary controlling factor may be different.     

基于PRECEDE-PROCEED模型的药剂师工作行为影响因素

目的：研究药剂师工作行为的影响因素,促进药剂师工作行为的规范化。方法：基于PRECEDE-PROCEED模型,将影响药剂师工作行为的因素分为倾向因素、促成因素及加强因素,对浙江省15家医院,共计132名药剂师进行实地调研。结果：倾向因素平均分最高,其中最高分为4.51,最低分为4.32;促成因素处于中间水平,其中最高分为4.04,最低分为3.30;加强因素平均分最低,其中最高分为4.17,最低分为3.21。结论：倾向因素对于药剂师工作行为的影响最大,促成因素次之,加强因素的影响效用最小。建议进一步发挥倾向因素的积极影响作用,同时改善促成因素与加强因素,使药剂师工作行为向更加高效、优质的方向改进。     

Activation of bovine factor V by an activator purified from the venom of Naja naja oxiana.

The crude venom of many elapid snakes appeared to contain proteins that activated blood coagulation factor V. The factor V activator present in the venom of Naja naja oxiana was purified to homogeneity by chromatography on a mono-S column. The activator was a single chain protein with an apparent mol. wt of 48,000, as judged by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and by gel permeation chromatography on Sephacryl S200. Activation of bovine factor V by the purified venom activator was accompanied by proteolytic cleavage of factor V and resulted in the formation of two major polypeptide chains with mol. wts of about 90,000 and 77,000. The final product obtained was compared with thrombin-activated factor V for its ability to function as cofactor in factor Xa-catalysed prothrombin activation in the presence of negatively charged phospholipid vesicles (5 mole% phosphatidylserine/95 mole% phosphatidylcholine). The Km for prothrombin obtained at a saturating amount of venom-activated factor Va was nine-fold higher than with thrombin-activated factor V (0.83 microM vs 0.09 microM, respectively) whereas both factor Va molecules stimulated the Vmax of thrombin formation some 6000-fold. Both forms of factor Va promoted the binding factor Xa to negatively charged phospholipid vesicles. However, the apparent Kd for factor Xa was less favorable in the presence of venom-activated factor V (0.67 x 10(-9) M) than in the presence of thrombin-activated factor V (0.043 x 10(-9) M). Thrombin cleaved a peptide bond in the 77,000 mol. wt polypeptide chain of venom-activated factor V, which resulted in the formation of a normal factor Va light chain. This peptide bond cleavage was, however, not associated with a change of cofactor activity. Venom treatment of thrombin-activated factor V, on the other hand, did remove a small fragment (mol. wt approximately 4000) from the heavy chain of factor Va (94,000), yielding a molecule with reduced cofactor activity. The diminished cofactor activity of venom-activated factor V is, therefore, likely due to the fact that a small peptide fragment, involved in the interaction with prothrombin and factor Xa, is missing from the heavy chain of venom-activated factor V.     

猪凝血因子V的制备及其活性分析

从猪血浆中制备猪凝血因子V,并分析凝血因子V加速凝血酶原活化的促凝活性。采用聚乙二醇沉淀、柠檬酸钡吸附、DEAE纤维素离子交换层析等方法,制备了猪凝血因子V。经SDSPAGE检测,猪凝血因子V得以成功制备,收率为每升血浆收90.2mg,纯度为64.4%。经纤维蛋白凝结实验分析,采用上述方法制备的猪凝血因子V具有较高的促凝血酶原活化活性。     

Recent advances in the discovery of tissue factor/factor VIIa inhibitors and dual inhibitors of factor VIIa/factor Xa

The search for an ideal anticoagulant has spanned decades and has taken several approaches to the identification of novel target molecules for preventing and treating thrombosis. In the group of anticoagulants acting through direct inhibition of coagulation factors, most research has focused on thrombin and factor Xa inhibitors. Attention has been drawn most recently to factor VIIa as a promising anticoagulation target, because of its role in complex with tissue factor, in initiating the coagulation cascade following blood vessel damage. Several reports suggest that inhibitors of the tissue factor/factor VIIa complex prevent thrombosis with a lower bleeding risk than other types of inhibitors. Accordingly, there is increasing interest in the generation of potent and selective small-molecule factor VIIa inhibitors that can be safely administered once or twice daily in an oral formulation with no need for routine coagulation monitoring. The emphasis of this review will be placed on recent advances in the development of the small-molecule inhibitors of factor VIIa complexed with tissue factor. The role of factor VIIa and tissue factor as initiators of the coagulation cascade following blood vessel damage is described, along with the structure of the active site of factor VIIa.     

社区糖尿病危险因素与慢性并发症的关联性

目的了解社区2型糖尿病(T2dM)人群发病危险因素的聚集与慢性并发症变化的关系。方法在城市社区就诊患者中选取159例2型糖尿患者,进行糖尿病人群危险因素调查、体格指标测量和生化指标检测。结果①在159例糖尿病者中,诊断具有糖尿病危险因素者103人(占64.8%),其慢性并发症发生率明显高于不伴有糖尿病危险因素者(P<0.01)。②logistic回归分析结果显示,以不伴糖尿病危险因素和只有一个危险因素组为参照,有2个危险因素组、3个危险因素组、4个危险因素组和5个危险因素组增加慢性并发症发生率的OR值分别为1.401(95%CI:0.811～3.014),2.614(95%CI:1.822～7.012)、3.241(95%CI:2.128～8.652)和4.991(95%CI:3.019～9.662)。结论糖尿病发病危险因素影响慢性并发症的变化,且随着危险因素的增加,慢性并发症有增多的趋势。     

Determination of factor VIII-coagulation antigen in factor VIII concentrates using an inhibitor test

The method of determination of factor VIII coagulation antigen (VIIICAg) here described is based on the well established factor VIII inhibitor test. Highly concentrated inhibitors to factor VIII in factor VIII substituted hemophiliacs are the most frequent among inhibitors to clotting factors. If such an inhibitor is used in an inhibitor assay its reaction depends on the VIIICAg concentration in the test system. The slope of the reaction curve is proportional to VIIICAg if the inhibitor titer is known. VIIICAg was measured in one cryoprecipitate and 5 different factor VIII concentrates of medium to high purity using this assay. In addition factor VIII related antigen and factor VIII ristocetin cofactor were determined by routine methods. VIIICAg fairly corresponded to factor VIII coagulation activity. Only cryoprecipitate contained significantly more VIIICAg.     

Activation of human vascular endothelial cells by factor Xa: effect of specific inhibitors

Recently, human umbilical vein endothelial cells (HUVEC) have been shown to express functional high-affinity receptors for factor Xa, which may be of importance in the regulation of coagulation and homeostasis of the vascular wall. In this paper, we demonstrate that when added to cultured HUVEC, factor Xa was a potent mitogen, stimulating an increase in cell number at a 0.3 to 100 nM concentration. The same doses of factor Xa also increased intracellular free calcium levels and phosphoinositide turnover. When added to confluent HUVEC, factor Xa induced the expression of tissue factor and the release of tissue-type plasminogen activator and plasminogen activator inhibitor-1 without affecting urokinase expression. Indirect (antithrombin-pentasaccharide) and direct (DX9065) inhibitors of factor Xa affected all these activities of factor Xa in a dose-dependent manner. Taken together, these data show that the activities induced by factor Xa on HUVEC were dependent on its catalytic activity and could be inhibited by both direct and indirect factor Xa inhibitors.     

Recombinant factor VIIa (Eptacog Alfa): a review of its use in congenital or acquired haemophilia and other congenital bleeding disorders

Recombinant factor VIIa (NovoSeven) [also known as recombinant activated factor VII or eptacog alfa] is a vitamin K-dependent glycoprotein that is structurally similar to human plasma-derived factor VIIa. It is a recombinant product, manufactured using DNA biotechnology. Intravenous recombinant factor VIIa has been evaluated in the treatment of bleeding episodes and for providing haemostasis cover during surgery in patients with certain bleeding disorders. Large, well controlled trials of recombinant factor VIIa have not been performed because of the rarity of these bleeding disorders. However, the efficacy of recombinant factor VIIa has been investigated in these patients in double-blind dose-finding or noncomparative clinical trials and worldwide compassionate-use programmes. Recombinant factor VIIa is effective and generally well tolerated in patients with haemophilia A or B with inhibitors, those with acquired haemophilia or Glanzmann's thrombasthenia. Also, recombinant factor VIIa is a treatment of choice in patients with haemophilia B with high-responding inhibitors and those with factor VII deficiency. Direct head-to-head comparisons and robust pharmacoeconomic data are required to fully determine the position of recombinant factor VIIa in relation to other therapies. Importantly though, the product appears to be relatively free of antigenicity, thrombogenicity and risk of viral transmission that, in the past, have limited the utility of blood products. Given that these characteristics are important determinants of the place of a treatment in bleeding disorders, recombinant factor VIIa provides a valuable treatment alternative in patients with haemophilia with inhibitors, platelet-refractory Glanzmann's thrombasthenia or congenital factor VII deficiency.