血管内皮生长因子及其受体在抗肿瘤血管生成中的研究进展

肿瘤生长和转移依赖于血管生成，肿瘤血管生成是一多因素、多步骤的复杂过程，受多种细胞因子、生长因子及其受体调控，其中血管内皮生长因子(VEGF)及其受体(VEGFR)被认为是最关键的调控因子，封闭VEGF功能和以VEGFR为靶点的抗肿瘤血管生成成为抗肿瘤的新策略。     

血管内皮生长因子对肿瘤血管生成影响的研究进展

血管内皮生长因子（VEGF）是血管生成的主要调控因子，其特异性地作用于血管内皮细胞，促进内皮细胞的增殖与迁移，对肿瘤血管的形成意义重大。经过多年研究，VEGF在肿瘤血管生成中的地位已被确定，并将在肿瘤的诊断、治疗、判断预后等方面发挥更加重要的的作用。本文就VEGF与肿瘤血管生成关系的研究作以简单综述。     

血管内皮生长因子的研究进展

血管内皮生长因子（VEGF）是血管生成的主要调控因子，特异性地作用于血管内皮细胞。VEGF受体特异性地分布于血管内皮细胞，促进内皮细胞的增殖和迁移。本文就VEGF的分子特征、VEGF受体及信号转导、VEGF及受体的表达调控作一综述。     

血管内皮生长因子的研究进展

血管内皮生长因子(VEGF)是血管生成的主要调控因子,特异性地作用于血管内皮细胞。VEGF受体特异性地分布于血管内皮细胞,促进内皮细胞的增殖和迁移。本文就VEGF的分子特征、VEGF受体及信号转导、VEGF及受体的表达调控作一综述。     

血管内皮生长因子与抗肿瘤研究进展

血管内皮生长因子(VEGF)在实体瘤的发生、发展及转移过程中起重要作用,并且是实体瘤预后的一项独立指标。恶性肿瘤细胞亦高水平表达VEGF,且与肿瘤血管新生密切相关,VEGF还作用于肿瘤细胞表面特异性受体,促进肿瘤细胞增殖,阻止肿瘤细胞凋亡,也是恶性肿瘤独立的预后指标。抗新生血管治疗的靶点是新生的肿瘤血管,以VEGF及其受体(VEGFR)为靶向的血管新生抑制药物的研发,得到了广泛的重视。随着抑制肿瘤新生血管的基础研究、临床试验技术和其他相关技术的不断发展,抑制肿瘤新生血管的药物开发和临床应用会达到更成熟的阶段。     

血管内皮生长因子及其受体与肿瘤

血管内皮生长因子（VEGF）及其受体（VEGFR）在肿瘤的生长和转移中起着重要的调节作用，已越来越成为人们研究的热点。本文就VEGF和VEGF家族成员，它们与肿瘤生长转移的关系以及VEGF和VEGFR与肿瘤治疗作一综述。     

血管内皮生长因子受体研究进展

血管内皮生长因子 (ＶＥＧＦ)是一类与肝素结合的生长因子 ,对血管内皮细胞具特异的致分裂作用 ,可促使内皮细胞分裂增殖 ,促进新血管的形成 ,同时还可有效地提高血管的通透性。而ＶＥＧＦ的这些生物效应是通过其特异性受体ＶＥＧＦＲ介导的。ＶＥＧＦＲ主要有两种 ,ｆｍｓ样酪氨酸激酶 (ｆｍｓ ｌｉｋｅｔｙｒｏｓｉｎｅｋｉｎａｓｅ ,ｆｌｔ 1 )为第一类受体 ,含激酶插入区受体 (ｋｉｎａｓｅｉｎ ｓｅｒｔｄｏｍａｉｎ ｃｏｎｔａｉｎｉｎｇｒｅｃｅｐｔｏｒ ,ＫＤＲ)为第二类受体。这两类受体属于酪氨酸激酶受体家族 ,在胚胎发育、伤口…     

血管生成、血管内皮生长因子与恶性血液病

恶性血液病发生发展与血管生成和血管内皮生长因子（VEGF）的关系日益受到人们的关注。本文综述了各种类型的白血病、淋巴瘤、多发性骨髓瘤（MM）、骨髓增生异常综合征（MDS）等骨髓血管生成情况、血液VEGF水平的观察结果,及其与疾病的诊断、预后的关系。并介绍了抗血管生成治疗在恶性血液病应用的初步结果。抗血管治疗有可能成为恶性血液病治疗中的一个新的靶点。     

血管内皮生长因子及其受体对类风湿关节炎新生血管的影响

目的:探讨血管内皮生长因子及其受体与类风湿关节炎新生血管的关系。资料来源:应用计算机检索Pubmed2000-01/2005-02有关血管内皮生长因子及其受体对类风湿关节炎血管新生的影响的文献,检索词“vascularendothelialgrowthfactor,vascularendothelialgrowthfactorreceptor,rheumatoidarthritis,angiogenesis”,并限定文章语言种类为English。资料选择:对检索到的血管内皮生长因子及其受体与类风湿关节炎血管新生方面的相关信息进行整理,选取针对性强的文章。同一领域的文献则选择近期发表或权威杂志的文章。资料提炼:共检索到37篇相关文献,其中19篇文章符合要求。排除18篇,其中15篇系重复同一研究,3篇为Meta分析。资料综合:血管内皮生长因子通过与其受体结合发挥生物学作用,促进内皮细胞有丝分裂,进一步增殖分化、迁移,导致血管新生,形成血管翳,在类风湿关节炎的病理过程中起关键作用。针对血管内皮生长因子从不同水平进行抗血管新生治疗类风湿关节炎取得了显著效果,为治疗类风湿关节炎提供了新的策略。结论:血管内皮生长因子在类风湿关节炎病理性新生血管化过程中所起的作用已基本肯定,但其作用途径尚未完全明确。抗血管新生从理论上为治愈类风湿关节炎提供了可能,但该类药物的安全性及更为精细的治疗靶点都有待于进一步探索。     

血管内皮生长因子及其受体对类风湿关节炎新生血管的影响

目的：探讨血管内皮生长因子及其受体与类风湿关节炎新生血管的关系.资料来源：应用计算机检索Pubmed 2000-01/2005-02有关血管内皮生长因子及其受体对类风湿关节炎血管新生的影响的文献,检索词＂vascular endothelial growth factor,vascular endothelial growth factor receptor,rheumatoid arthritis,angiogenesis＂,并限定文章语言种类为Ennlish.资料选择：对检索到的血管内皮生长因子及其受体与类风湿关节炎血管新生方面的相关信息进行整理,选取针对性强的文章.同一领域的文献则选择近期发表或权威杂志的文章.资料提炼：共检索到37篇相关文献,其中19篇文章符合要求.排除18篇,其中15篇系重复同一研究,3篇为Meta分析.资料综合：血管内皮生长因子通过与其受体结合发挥生物学作用,促进内皮细胞有丝分裂,进一步增殖分化、迁移,导致血管新生,形成血管翳,在类风湿关节炎的病理过程中起关键作用.针对血管内皮生长因子从不同水平进行抗血管新生治疗类风湿关节炎取得了显著效果,为治疗类风湿关节炎提供了新的策略.结论：血管内皮生长因子在类风湿关节炎病理性新生血管化过程中所起的作用已基本肯定,但其作用途径尚未完全明确.抗血管新生从理论上为治愈类风湿关节炎提供了可能,但该类药物的安全性及更为精细的治疗靶点都有待于进一步探索.     

Role of vascular endothelial growth factor receptor 1 and vascular endothelial growth factor receptor 2 in the vasodilator response to vascular endothelial growth factor in the neonatal piglet lung

OBJECTIVE: Vascular endothelial growth factor (VEGF) regulates vascular proliferation and causes vasodilation. In the pulmonary circulation, the vasorelaxing effect of VEGF has been attributed to nitric oxide, whereas in other vascular beds, prostacyclin and other mechanisms are also involved. This vascular effect follows binding to two receptors, VEGF receptor 1 (VEGFR1) and VEGF receptor 2 (VEGFR2), the latter of which is thought to be the main receptor responsible for the vasorelaxing effect of VEGF. The role of VEGFR1 in the neonatal pulmonary vasculature remains to be determined. DESIGN: Prospective randomized laboratory investigation. SETTING: Animal laboratory. SUBJECTS: Newborn Yorkshire-Landrace piglets. INTERVENTIONS: To determine the mechanisms of action of VEGF in the neonatal pulmonary vasculature, the effect of VEGF (10-10 M) was tested in isolated perfused piglet lungs, alone and in the presence of a VEGFR2 kinase inhibitor, N-nitro-l-arginine (L-NNA), indomethacin (Indo), L-NNA + Indo, and GF109203X, a protein kinase C inhibitor. The effect of a VEGFR1 agonist, placenta growth factor (PlGF), was also studied with or without L-NNA. Perfusate was collected, and cyclic guanosine monophosphate (cGMP), as well as 6-keto prostaglandin F1alpha and thromboxane B2, the stable metabolites of prostacyclin and thromboxane, respectively, was measured. MEASUREMENTS AND MAIN RESULTS: VEGF caused vasorelaxation with a concomitant increase in cGMP. PlGF also decreased vascular tone and increased cGMP. VEGFR2 kinase inhibitor did not prevent the reduction in perfusion pressure seen with VEGF but blocked the increase in cGMP. Pretreatment with L-NNA completely inhibited VEGF and PlGF vasodilation and prevented the increase in cGMP seen with both agonists. Pretreatment with Indo or GF109203X did not reduce the dilator response to VEGF. CONCLUSIONS: VEGF vasodilation may follow nitric oxide release in the piglet pulmonary circulation. VEGF vasorelaxation may not only occur through binding to VEGFR2, since PlGF, the specific VEGFR1 agonist, also causes vasodilation. Therefore, vasodilator response to VEGF may involve both types of receptor in the neonatal piglet pulmonary vasculature.     

血管内皮生长因子及其受体在肺损伤中作用的研究进展

血管内皮生长因子(VEGF)既是一种多能性的生长因子,又是一种通透因子,在正常肺组织中大量表达,通过血管内皮生长因子受体(VEGFR)发挥其生理作用,具有促有丝分裂、血管生成和内皮细胞存活,增加血管通透性等作用,在急性肺损伤的发生、发展及转归中是一把双刃剑,其作用日益引起人们的重视.通过对VEGF在ALI/ARDS不同阶段中的作用的研究,有望为ALI/ARDS的药物治疗提供理论依据.     

真核表达载体血管内皮生长因子转染血管内皮细胞及对新生血管形成的影响

背景:血管内皮生长因子(vascular endothelial growth factor,VEGF)能与存在内皮细胞表面的特异性受体结合,刺激体内新生血管形成,但在体内半衰期极短,在移植局部难以维持足够的浓度,限制了其临床应用.目的:观察VEGF与增强绿色荧光蛋白(enhanced green fluorescent,EGFP)共表达载体转染对大鼠血管内皮细胞形成新生血管的影响.设计、时间及地点:随机分组设计、对照动物实验,于2004-09/2005-01在中国医科大学附属第一医院器官移植实验室完成.材料:30只雄性Wistar大鼠按随机数字表法分为3组,每组10只.质粒pIRES2-EGFP/VEGF165由第四军医大学提供.方法:采用层析法大量提取pIRES2-EGFPNEGF165质粒,采用阳性脂质体法进行转染,计数1×106血管内皮细胞植入雄性Wiser大鼠肾被膜下.实验组:植入转染质粒pIRES2-EGFP/VEGF165的内皮细胞:空白转染组:植入转染质粒pIRES2-EGFP的内皮细胞:对照组:植入正常大鼠血管内皮细胞.主要观察指标:①转染72 h后观察EGFP及VEGF表达情况.②流式细胞仪检测转染效率.③植入后14 d苏木精-伊红染色观察植入血管内皮细胞处组织形态学变化.结果:30只大鼠均进入结果分析.①荧光显微镜下实验组内皮细胞有特异性的EGFP表达.②流式细胞仪分析转染效率为13.06%.③实验组血管内皮细胞胞核和胞浆中均有VEGF表达.反转录-聚合酶链反应显示实验组大鼠血管内皮细胞中有人源化VEGF165基因在mRNA水平表达.④移植后14 d.实验组大鼠肾被膜下可见成团的新生毛细血管网形成,而对照组及空白转染组虽血管内皮细胞仍存活,但未形成明显血窦.结论:转染VEGF基因是促进内皮细胞早期(14d内)形成新生血管的有效途径.     

血管内皮生长因子及其受体在门静脉高压性胃病中的表达及其意义

目的 探讨血管内皮生长因子（VEGF）及其受体FLT-1、FLK-1mRNA在门静脉高压性胃病（PHG）中的作用。方法 采用逆转录聚合酶链反应（RT-PER）对44例肝硬化门静脉高压症患者PHG动态变化过程中病变部位的VEGF、FLT-1及FLK-1mRNA的表达进行检测。结果 轻度胃病组VEGF、FLT-1、FLK-1mRNA的表达量分别为（2．28±0．33）、（0．59±0．17）和（0.56±0．14），与无胃病组及正常对照组比较差异均有显著性（均P〈0．01）；重度胃病组VEGF、FLT-1、FLK-1mRNA分别为（3．48±1．02）、（0．68±0．20）和（0.71±0．18），与轻度胃病组、无胃病组及正常对照组比较差异均有显著性（均P〈0．01）。结论 VEGF及其受体FLT-1、FLK-1过度表达是胃病胃黏膜损害的重要因素之一。     

Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis.

Vascular permeability factor (VPF) is an Mr 40-kD protein that has been purified from the conditioned medium of guinea pig line 10 tumor cells grown in vitro, and increases fluid permeability from blood vessels when injected intradermally. Addition of VPF to cultures of vascular endothelial cells in vitro unexpectedly stimulated cellular proliferation. VPF promoted the growth of new blood vessels when administered into healing rabbit bone grafts or rat corneas. The identity of the growth factor activity with VPF was established in four ways: (a) the molecular weight of the activity in preparative SDS-PAGE was the same as VPF (Mr approximately 40 kD); (b) multiple isoforms (pI greater than or equal to 8) for both VPF and the growth-promoting activity were observed; (c) a single, unique NH2-terminal amino acid sequence was obtained; (d) both growth factor and permeability-enhancing activities were immunoadsorbed using antipeptide IgG that recognized the amino terminus of VPF. Furthermore, 125I-VPF was shown to bind specifically and with high affinity to endothelial cells in vitro and could be chemically cross-linked to a high-molecular weight cell surface receptor, thus demonstrating a mechanism whereby VPF can interact directly with endothelial cells. Unlike other endothelial cell growth factors, VPF did not stimulate [3H]thymidine incorporation or promote growth of other cell types including mouse 3T3 fibroblasts or bovine smooth muscle cells. VPF, therefore, appears to be unique in its ability to specifically promote increased vascular permeability, endothelial cell growth, and angio-genesis.     

乳腺癌中血管内皮生长因子受体KDR的表达及其意义

目的 研究乳腺癌中血管内皮生长因子受体（vascular endothelial growth factor receptor2，VEGFR2）KDR的表达情况及其与微血管密度（microvessel density，MVD）关系。方法对98例乳腺癌患者的病理标本应用CDM，KDR分别进行免疫组化染色。双盲法计数热点内血管测定MVD，并进行统计学分析。结果乳腺癌KDR在血管周围的肿瘤细胞质呈较强阳性表达，在部分血管内皮细胞质内表达呈弱阳性，KDR表达与MVD有统计学意义（P＜0．05）。结论KDR在乳腺癌细胞的高度表达可能参与乳腺癌的发病机制，为乳腺癌的治疗提供新的思路。     

Comparison of vascular endothelial growth factor and basic fibroblast growth factor on angiogenesis in SCID mice.

Therapeutic angiogenesis is a promising approach to treat patients with cardiovascular disease, and will likely be critical to engineering large tissues. Many growth factors have been found to play significant roles in angiogenesis, and vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are the most extensively investigated angiogenic factors to date. However, the appropriate dose to obtain a desired response and the effectiveness of each factor, relative to the other, in promoting angiogenesis at a specific site in the body remains unclear. We have used alginate hydrogels as localized delivery vehicles for VEGF and bFGF, and compared the ability of these factors to promote new blood vessel formation in the subcutaneous tissue of severe combined immunodeficient (SCID) mice. We have found that the thickness of a granulation tissue layer formed around the gel and the number of blood vessels in the layer increased with the dose of VEGF in the gel, but the density of new blood vessels remained relatively constant. Sustained and localized delivery of bFGF from the gels, while similarly leading to an increase in the density of blood vessels in the granulation tissue, did not lead to as high of a blood vessel density as VEGF. The results of this study support previous studies demonstrating the utility of both VEGF and bFGF in promoting angiogenesis, and suggest VEGF is more appropriate for creating a dense bed of new blood vessels in this model.