乳腺癌淋巴管密度与血管内皮生长因子C相关性分析

目的 探讨乳腺癌组织内淋巴管密度（LVD）与血管内皮生长因子C（VEGF-C）的相关性。方法收集我院2006至2009年乳腺癌患者标本40例,另取乳腺纤维瘤组织标本5例,正常乳腺组织标本5例;采用酶组织化学双重染色法,对50例乳腺组织标本的LVD进行了检测和分析。同时采用免疫组化SP法检测50例乳腺组织标本VEGF-C的表达。结果乳腺癌组织的LVD、VEGF-C阳性表达率明显高于对照组（P〈0．05）。乳腺癌淋巴结转移阳性组LVD、VEGF．C阳性表达率均明显高于淋巴结转移阴性组（P〈0．05）。乳腺癌LVD与VEGF．C的表达成正相关（P〈0．05）。结论乳腺癌组织中LVD、VEGF—C表达水平增高,LVD与VEGF-C的表达促进乳腺癌淋巴结的转移。     

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。     

血管内皮生长因子C表达与宫颈鳞状细胞癌局部淋巴管血管生成和浸润转移及预后的关系

目的 探讨血管内皮生长因子C（VEGF-C）表达与宫颈鳞状细胞癌局部淋巴管血管生成、浸润转移及预后的关系.方法 采用免疫组织化学法检测28例正常宫颈上皮、36例宫颈上皮内瘤变和68例宫颈鳞状细胞癌组织VEGF-C表达,同时检测血管内皮生长因子受体3（VEGFR-3）标记的微淋巴管密度、Ki-67标记的增殖指数和CD34标记的微血管密度.结果 VEGF-C在正常宫颈上皮组、宫颈上皮内瘤变组和宫颈鳞状细胞癌组的阳性表达率分别为21.43%、61.11%和72.06%,从正常宫颈上皮组到宫颈上皮内瘤变组及宫颈鳞状细胞癌,VEGF-C表达明显升高（P＜0.01）.在宫颈上皮内瘤变组,VEGF-C表达与微血管密度明显正相关（r=0.199,P=0.048）,VEGF-C阳性表达者微血管密度明显高于VEGF-C阴性表达者（F=4.112,P=0.049）.在宫颈鳞状细胞癌组,VEGF-C表达与微淋巴管密度显著正相关（r=0.288,P=0.017）,VEGF-C阳性表达者微淋巴管密度显著高于VEGF-C阴性表达者（F=6.488,P=0.013）.VEGF-C在宫颈鳞状细胞癌组表达与增殖指数及微血管密度均无显著相关性（增殖指数：r=0.085,P=0.489 微血管密度：r=0.181,P=0.139）.VEGF-C在宫颈鳞状细胞癌组表达与盆腔淋巴结转移、脉管浸润及生存率密切相关（P＜0.05）,而与患者年龄、国际妇产科协会（FIGO）分期、组织学分级及间质浸润深度无关（P＞0.05）.VEGF-C阳性表达者盆腔淋巴结转移及脉管浸润的发生率分别明显高于VEGF-C阴性表达者（P＜0.05）,而VEGF-C阳性表达者生存率明显低于VEGF-C阴性表达者（Log rank检验,P=0.0357）.结论 宫颈鳞状细胞癌VEGF-C过度表达可能促进局部淋巴管生成及肿瘤转移,可能提示预后不良.     

血管内皮生长因子

血管内皮生长因子是一类能够特异地作用于血管内皮细胞,通过特异性受体发挥生物学作用的血管生长调控因子。促进内皮细胞增生;增加细胞质钙离子浓度;增加血管渗透性,改变细胞外基质,促进血管生成,其中一些因子还在淋巴管生成中起作用。本文对血管内皮生长因子的特征、生物学作用等进行了综述。     

血管内皮生长因子C表达与宫颈鳞状细胞癌局部淋巴管血管生成和浸润转移及预后的关系

Objective To examine the relation among the expression of vascular endothelial growth factor C (VEGF-C) and regional lymphangiogenesis, invasion, metastasis and prognosis in squamous cell carcinoma of cervix.Methods The expression of VEGF-C, lymphatic microvessel density(LMVD) labeled by VEGFR-3, proliferation index (PI) of cancer cells labeled by Ki-67 and microvessel density (MVD) labeled by CD34 in 28 cases of normal cervical epithelium( NCE), 36 cases of cervical intraepithelial neoplasm( CIN ) and 68 cases of squamous carcinoma of cervix (SCC)were detected by immunohistochemistry method. Results The positive rates of expressions of VEGF-C in NCE, CIN and SCC group were 21.43% , 61.11% and 72.06%, respectively. The positive expression of VEGF-C increased remarkably from NCE to CIN and SCC accordingly ( P ＜ 0. 01 ). The expression of VEGF-C in CIN significantly related to MVD ( r =0. 199, P =0. 048). The MVD in the cases with positively expressed VEGF-C in CIN was significantly higher than that with negatively VEGF-C expressed (F =4.112, P = 0. 049 ). The expression of VEGF-C in SCC significantly correlated with LMVD(r=0.288,P=0.017), but not with PI(r=0.085, P=0.489) and MVD(r=0. 181, P=0. 139). The LMVD in the cases with positively expressed VEGF-C in SCC was remarkably higher than that with negatively VEGF-C expressed ( F =6.488, P =0. 013 ). The expression of VEGF-C in SCC significantly related to pelvic lymph node metastasis, intravascular infiltration and survival rate (P ＜0.05 ), but not to patients' age, FIGO staging, histological grading, and depth of stroma infiltration (P ＞0.05 ). In the cases with VEGF-C positive expression in SCC group, the rate of pelvic lymph node metastasis and intravascular infiltration was significantly higher than that in those without the conditions mentioned above ( P ＜0.05 ). The patients' survival rate in the VEGF-C positively expressed cases in SCC group was significantly lower compared with the negative cases ( log rank test, P = 0.0357 ). Conclusion The overexpression of VEGF-C in SCC may result in rapid regional lymphangiogenesis and tumor metastasis, showing a bad prognosis.     

血管内皮生长因子C表达与宫颈鳞状细胞癌局部淋巴管血管生成和浸润转移及预后的关系

Objective To examine the relation among the expression of vascular endothelial growth factor C (VEGF-C) and regional lymphangiogenesis, invasion, metastasis and prognosis in squamous cell carcinoma of cervix.Methods The expression of VEGF-C, lymphatic microvessel density(LMVD) labeled by VEGFR-3, proliferation index (PI) of cancer cells labeled by Ki-67 and microvessel density (MVD) labeled by CD34 in 28 cases of normal cervical epithelium( NCE), 36 cases of cervical intraepithelial neoplasm( CIN ) and 68 cases of squamous carcinoma of cervix (SCC)were detected by immunohistochemistry method. Results The positive rates of expressions of VEGF-C in NCE, CIN and SCC group were 21.43% , 61.11% and 72.06%, respectively. The positive expression of VEGF-C increased remarkably from NCE to CIN and SCC accordingly ( P ＜ 0. 01 ). The expression of VEGF-C in CIN significantly related to MVD ( r =0. 199, P =0. 048). The MVD in the cases with positively expressed VEGF-C in CIN was significantly higher than that with negatively VEGF-C expressed (F =4.112, P = 0. 049 ). The expression of VEGF-C in SCC significantly correlated with LMVD(r=0.288,P=0.017), but not with PI(r=0.085, P=0.489) and MVD(r=0. 181, P=0. 139). The LMVD in the cases with positively expressed VEGF-C in SCC was remarkably higher than that with negatively VEGF-C expressed ( F =6.488, P =0. 013 ). The expression of VEGF-C in SCC significantly related to pelvic lymph node metastasis, intravascular infiltration and survival rate (P ＜0.05 ), but not to patients' age, FIGO staging, histological grading, and depth of stroma infiltration (P ＞0.05 ). In the cases with VEGF-C positive expression in SCC group, the rate of pelvic lymph node metastasis and intravascular infiltration was significantly higher than that in those without the conditions mentioned above ( P ＜0.05 ). The patients' survival rate in the VEGF-C positively expressed cases in SCC group was significantly lower compared with the negative cases ( log rank test, P = 0.0357 ). Conclusion The overexpression of VEGF-C in SCC may result in rapid regional lymphangiogenesis and tumor metastasis, showing a bad prognosis.     

血管内皮生长因子C水平对膀胱癌诊断和预后评估的临床价值

目的分析探讨血管内皮生长因子C(VEGF-C)水平对膀胱癌诊断和预后评估的临床价值。方法 73例膀胱癌患者作为试验组,选择同期的健康体检者50例作为对照组,采用酶联免疫吸附法测定两组的血清VEGF-C水平。结果试验组患者的血清VEGF-C水平为(8.1±1.3)μg/L,对照组患者的血清VEGF-C水平为(4.1±0.8)μg/L,两组比较,差异具有统计学意义(P<0.05);血清低VEGF-C水平的膀胱癌患者其生存率高于血清高VEGF-C水平膀胱癌患者,比较差异具有统计学意义(P<0.05)。结论血清VEGF-C水平可作为膀胱癌病症的早期诊断以及判断预后的指标。     

血管内皮生长因子C及其受体表达与乳腺癌淋巴结转移的相关性研究

目的本研究旨在检测乳腺癌组织中VEGF-C/VEGFR-3、LVD的表达情况,探讨其表达水平淋巴结转移的相互关系,进一步研究肿瘤转移的机制,为抗淋巴管形成、进而为抗乳腺癌淋巴转移的治疗提供理论依据。方法应用免疫组织化学(SP)法检测83例乳腺癌手术标本的原发灶的VEGF-C及其受体VEGFR-3的表达及LVD。结果83例乳腺癌组织VEGF- C阳性表达者36例(43.3%),淋巴结转移组的VEGF-C阳性表达率为59.4%(24/44),显著高于无淋巴结转移组30.8%(24/44),(P<0.05);在VEGF-C表达阳性组、阴性组中LVD统计学上差异显著(P<0.05),结论乳腺癌组织VEGF-C表达可能促进肿瘤内淋巴管的生成;乳腺癌的淋巴结转移和VEGF-C的高表达密切相关。     

血管内皮生长因子与子宫内膜癌

血管内皮生长因子(vascular endothelial growth factor,VEGF)是一组功能强大且能产生多种效应的细胞因子.它可诱导血管及淋巴管生成,不仅在胚胎发育、创伤愈合中发挥重要作用,而且与肿瘤的生长、浸润和转移关系密切.子宫内膜癌是女性生殖道常见的三大恶性肿瘤之一,占女性生殖道恶性肿瘤的20%～30%,其发病率持续上升,且发病年龄有降低趋势[1].近年的研究表明,VEGF可能在子宫内膜癌的发生、发展、转移以及预后方面发挥重要作用.     

靶向血管内皮生长因子/血管内皮生长因子受体-2的血管生成抑制剂

血管内皮生长因子(VEGF)及血管内皮生长因子受体-2(VEGFR-2)是调节血管生成、内皮细胞增殖和迁移等的关键调控因子。通过阻断VEGF与VEGFR-2的结合可抑制新生血管形成,而新生血管的形成是肿瘤生长和转移的基础。介绍VEGF/VEGFR-2在血管形成中的作用,以及具有抗肿瘤作用的靶向VEGF/VEGFR-2的血管生成抑制剂的研究近况。     

反义核酸药物抑制大鼠C6胶质瘤生长的研究

目的：探讨血管内皮生长因子(VEGF)反义寡核苷酸(AODN)作为胶质瘤辅助治疗新途径的可能性.方法：在细胞培养和大鼠皮下胶质瘤模型中给予VEGF AODN处理后,S P法检测VEGF蛋白的表达,TUNEL法和电镜技术检测瘤细胞凋亡.结果：在体外AODN可抑制C6细胞VEGF蛋白的表达,其抑制作用随AODN浓度升高而增强,对照组的浓度为1.0,2.5,5.0,10.0 μmol·L 1 AODN的VEGF阳性率分别为82.10%,73.10%,70.00%,57.85%,53.20%.体内AODN使皮下肿瘤体积缩小,瘤细胞凋亡增加,瘤内坏死区扩大;电镜表明AODN治疗组微血管基膜增厚,管径变小.结论：VEGF AODN可作为胶质瘤治疗的一种辅助手段,具有临床应用前景.     

血管内皮生长因子与子宫内膜异位症

随着子宫内膜异位症（endometriosis,EMs）病因及发病机制研究的深入,备受大多数学者支持的内膜种植学说已无法合理解释绝大多数妇女经期存在经血逆流却只有少数发病这一现象。近年来,大量研究表明子宫内膜异位症的发生与种植部位新生血管的形成密切相关,认为经血逆流可能只是子宫内膜异位症发生的一个前提条件,而血供的建立和维持才是其发生的基本。而血管内皮生长因子作为目前所知作用最强的促血管生长因子,其与子宫内膜异位症的关系也因此成为人们研究的热点。     

血小板微颗粒对人脐静脉内皮细胞VEGF表达的影响

目的:探讨血小板微颗粒( PMPs)影响内皮细胞血管内皮生长因子(VEGF)释放的可能机制及其临床意义.方法:常规培养人脐静脉内皮细胞(HUVECs)CRL-1730,配制不同干预浓度的PMPs与HUVECs共培养不同时间,应用半定量逆转录聚合酶链反应技术测定内皮细胞VEGF、VEGFⅡ型受体Fh/KDR、磷脂酰肌醇-3激酶(PI3K)以及胞外信号调节激酶(ERK)mRNA的表达水平.结果:(1)VEGF mRNA的表达水平在0mg/L组高于PMPs10、30、50、100 mg/L干预组(均P＜0.05),VEGFⅡ型受体Flt/KDR mRNA表达水平在0mg/L组低于PMPs10、30、50、100 mg/L(均P＜ 0.05).ERK mRNA表达水平在PMPs50mg/L组高于0mg/L组(P=0.004),PI3K mRNA表达水平在PMPs100 mg/L组高于0 mg/L组(P=0.004).(2)50 mg/L PMPs干预细胞,VEGF mRNA的表达水平在0h组高于4h、24 h组(P＜0.05),KDR mRNA的表达水平在0h组低于4h、24h组(均P＜0.05),PI3K mRNA的表达水平在0h组低于24 h组(P=0.004).结论:PMPs可能通过VEGF受体,激活其下游信号转导通路,发挥促进血管和血管发生为基础的生物学效应.     

重组血管内皮生长因子的研究进展

血管内皮生长因子（Ｖａｓｃｕｌａｒ ｅｎｄｏｔｈｅｌｉａｌ ｇｒｏｗｔｈ ｆａｃｔｏｒ,ＶＥＧＦ）是１９８９年Ｆｅｒｒａｒａ等在牛垂体滤泡星状细胞体外培养液中首先纯化出来的。到目前为止已经发现了六个ＶＥＧＦ异构体,包括ＶＥＧＦ１２１,ＶＥＧＦ１４５,ＶＥＧＦ１６５,ＶＥＧＦ１８３,ＶＥＧＦ１８９,ＶＥＧＦ２０６。已经发现高亲和力的ＶＥＧＦ受体有两类,分别为Ｆｌｔ－１（Ｆｍｓ－ｌｉｋｅ ｔｙｒｏｓｉ     

Co-Expression of Vascular Endothelial Growth Factor and Interleukin-1 Receptor Antagonist Improves Human Islet Survival and Function

Purpose Ex vivo gene therapy approaches can improve the outcome of islet transplantation for treating type I diabetes. We have previously shown the improvement in islet function and vascularization following ex vivo transfection for human vascular endothelial growth factor (hVEGF) gene expression. In this study, we tested the hypothesis that co-expression of two genes, which target different challenges faced by islets post-transplantation, supplement each other to improve the survival and function of islets. We determined whether there is an additive effect of hVEGF and human interleukin-1 receptor antagonist (hIL-1Ra) gene expression in human islets.Materials and Methods Human islets were co-infected with adenoviral vectors encoding hVEGF and hIL-1Ra. Islets were then incubated with a cocktail of inflammatory cytokines (IL-1β+TNFα+IFNγ), and islet viability and function were determined. In vivo function was evaluated by transplanting islets under the kidney capsules of streptozotocin-induced non-obese diabetic severe combined immunodeficient (NOD-SCID) mice.Results Infection of human islets with Adv-hVEGF and/or Adv-hIL-1Ra inhibited expression of inducible nitric oxide synthase (iNOS), decreased the production of nitric oxide (NO), and prevented the loss of in vitro glucose-stimulated insulin response and viability. Moreover, co-expression of hVEGF and hIL-1Ra reduced the blood glucose level of mice, and increased the level of blood insulin and c-peptide upon glucose challenge.Conclusions Our results indicated that co-expression of genes that target different insults to transplanted islets can improve the outcome of islet transplantation better than either gene alone.     

Vascular Endothelial Growth Factor Signaling in Hypoxia and Inflammation

Infection, cancer and cardiovascular diseases are the major causes for morbidity and mortality in the United States according to the Center for Disease Control. The underlying etiology that contributes to the severity of these diseases is either hypoxia induced inflammation or inflammation resulting in hypoxia. Therefore, molecular mechanisms that regulate hypoxia-induced adaptive responses in cells are important areas of investigation. Oxygen availability is sensed by molecular switches which regulate synthesis and secretion of growth factors and inflammatory mediators. As a consequence, tissue microenvironment is altered by re-programming metabolic pathways, angiogenesis, vascular permeability, pH homeostasis to facilitate tissue remodeling. Hypoxia inducible factor (HIF) is the central mediator of hypoxic response. HIF regulates several hundred genes and vascular endothelial growth factor (VEGF) is one of the primary target genes. Understanding the regulation of HIF and its influence on inflammatory response offers unique opportunities for drug development to modulate inflammation and ischemia in pathological conditions.     

2,3-吲哚醌对血管内皮细胞生长因子的影响及作用机制研究

目的:研究2,3-吲哚醌在体外对人神经母瘤细胞(SH-SY5Y)分泌血管内皮细胞生长因子(VEGF)的影响,探讨其作用机制。方法:采用酶联免疫吸附测定法检测VEGF蛋白分泌水平;反转录-聚合酶链反应测定VEGF信使核糖核酸(mRNA)的相对表达水平;Western-blot测定磷酸化的有丝分裂原激活的蛋白激酶(pp42/pp44)的相对表达量。结果:2,3-吲哚醌作用细胞24h后,VEGF分泌量明显降低,mRNA相对表达水平下降,pp42/pp44的相对表达量降低。结论:2,3-吲哚醌能抑制SH-SY5Y细胞分泌VEGF蛋白和mRNA的表达,其作用可能与改变有丝分裂原激活的蛋白激酶磷酸化水平有关。     

Inhibition of Tumor Growth and Metastasis by Targeting Tumor-Associated Angiogenesis with Antagonists to the Receptors of Vascular Endothelial Growth Factor

Angiogenesis, the formation of new blood vessels, is essential for both tumor growth and metastasis. Recent advances in our understanding of the molecular mechanisms underlying the angiogenesis process and its regulation have led to the discovery of a variety of pharmaceutical agents with anti-angiogenic activity. The potential application of these angiogenesis inhibitors is currently under intense clinical and pre-clinical investigation. Compelling evidence suggests that vascular endothelial growth factor (VEGF) and its receptors play critical roles in tumor-associated angiogenesis, and that they represent good targets for therapeutic intervention. This has been demonstrated in a variety of animal tumor models in which disabling the function of VEGF and its receptors was shown to inhibit both tumor growth and metastasis. We have produced a panel of antibodies directed against the VEGF receptor 2, KDR/Flk-1. These antibodies potently block VEGF/KDR/Flk-1 interaction, and inhibit VEGF-stimulated activation of the receptor and proliferation of human endothelial cells. Further, the antibodies significantly inhibited tumor-associated angiogenesis in several animal models. Antagonists of VEGF and/or its receptors may offer higher specificity towards tumors with reduced side effects, and may be less likely to elicit drug resistance compared to conventional therapy. Anti-angiogenesis therapy represents a novel strategy for the treatment of cancer and other human disorders where pathological angiogenesis is involved.     

SREBPS及VEGF调节辛伐他汀对血管平滑肌细胞的作用

目的观察辛伐他汀对血管平滑肌细胞作用,是否通过SREBPs及VEGF的调节起作用,SREBPs与VEGF之间相互关系。方法①体外培养大鼠血管平滑肌细胞(VSMCs),观察辛伐他汀对VSMCs增殖、迁移的影响及SREBPs、VEGF的mRNA表达。②建立大鼠动脉粥样硬化血管损伤模型,分为NC组、AI,组、LS组和HS组。药物干预4周后测定各组血脂、胸主动脉内膜/(内膜+中膜)比值及血管SREBPs、VEGF的mRNA表达。结果实验证明,大剂量辛伐他汀明显抑制VSMCs增殖和迁移,VSMCs的SREBP-1、SREBP-2的mRNA表达显著增加同时VEGF的表达显着减少,SREBPs与VEGF之间有一定的相关性。结论辛伐他汀抑制血管平滑肌细胞增殖和迁移机制可能是通过增加VSMCs的SREBPs的表达进而减少VEGF表达。     

舌癌血管内皮细胞生长因子-D表达与淋巴结转移的关系

目的:检测血管内皮生长因子-D(VEGF-D)在舌癌中的表达,探讨其与淋巴管密度及淋巴转移的关系.方法:采用免疫组化法检测62例舌癌中VEGF-D和淋巴管内皮细胞透明质酸受体(LYVE-1)的表达及定位.结果:VEGF-D在肿瘤细胞胞质中表达,LYVE-1在癌周淋巴管内皮细胞表达.62例舌癌中,VEGF-D的阳性表达率为74.2%(46/62),LYVE-1阳性表达率为83.9%(52/62),随着VEGF-D表达强度的增加,LYVE-1阳性淋巴管密度也增加(r=0.632,P＜0.05).中低分化舌癌VEGF-D的表达明显高于高分化(P＜0.05),有淋巴转移组VEGF-D的表达要高于无淋巴转移组(P＜0.05),但VEGF-D的表达与患者年龄、性别及临床分期无关.结论:VEGF-D由肿瘤细胞分泌,诱导舌癌癌周淋巴管增殖,促进肿瘤细胞淋巴转移.