血管内皮生长因子和微血管密度在食管癌组织中的意义

目的 :探讨血管内皮生长因子 (VEGF)蛋白表达和微血管密度 (MVD)与食管癌临床病理的关系。方法 :应用免疫组织化学SABC法 ,以鼠抗VEGF、兔抗FⅧRAg、UEA 1抗体标记 5 2例食管癌和 5例正常食管黏膜 ,观察其在不同分化程度、浸润深度和有无淋巴结转移食管癌中的表达及MVD情况。结果 :癌组织VEGF阳性 2 8例 (5 3 9% ) ,MVD平均为 5 1 3± 14 8。VEGF蛋白表达和MVD与癌组织分化程度、淋巴结转移有关 (P <0 0 5 ,P <0 0 1) ;与癌组织浸润深度无关 (P >0 0 5 )。结论 :提示VEGF与癌组织血管发生密切相关 ,VEGF蛋白表达和MVD可作为判断食管癌的恶性程度和预后的生物学指标     

血管内皮生长因子与肿瘤坏死因子-α在佐剂关节炎大鼠滑膜中表达

目的:探讨血管内皮生长因子(VEGF)和肿瘤坏死因子-α(TNF-α)在佐剂关节炎(AA)大鼠滑膜组织中的表达及其与关节病理积分的关系。方法:建立AA大鼠模型,常规HE染色,计算关节病理积分,并用免疫组织化学染色检测VEGF和TNF-α蛋白表达。结果:AA组大鼠滑膜VEGF和TNF-α蛋白表达在3周、8周及20周时均明显高于健康对照组(均P<0.01),且二者均与关节病理积分呈显著正相关(均P<0.01),二者之间亦呈显著正相关(均P<0.01)。结论:VEGF和TNF-α在关节炎的形成及发展过程中起重要作用,二者互相作用并影响滑膜新生血管的形成。     

血管内皮生长因子,微血管密度与乳腺癌淋巴结转移及预后？…

目的　探讨血管内皮生长因子 (VEGF)、微血管密度 (MVD)与乳腺癌淋巴结转移和预后的关系。方法　应用逆转录 聚合酶链反应 (RT PCR)与免疫组织化学SP法 ,检测 92例乳腺癌、12例癌旁组织V组织VEGF表达、MVD以及 2 1例乳腺癌、12例癌旁组织VEGFmRNA的表达。结果　乳腺癌组织 ,VEGF12 1(1.16 %± 0 1% )和VEGF165(1.0 1%± 0 .1% )表达高于癌旁组织 (0 .96 %± 0 .14% )、(0 .88%± 0 .1% ) ,P <0 .0 5～ 0 .0 1。此外 ,MVD与VEGF表达具有显著的正相关关系 (r =0 .70 2 ,P <0 .0 1)。VEGF表达和MVD与乳腺癌淋巴结转移、肿瘤复发关系密切 (P <0 .0 5～ 0 .0 1)。VEGF高表达组和高MVD组的无复发存活时间低于VEGF低表达组和低MVD组 ,差异具有非常显著性 (P <0 0 1)。结论　VEGF与乳腺癌血管生成密切相关 ;VEGF和MVD表达的增高对乳腺癌淋巴结转移、肿瘤复发有促进作用 ;VEGF和MVD对乳腺癌患者的无复发存活时间能起到预测作用     

人肝癌组织中CD34和血管内皮生长因子的表达及微血管密度的 …

目的 探讨ＣＤ３４和血管内皮生长因子（ＶＥＧＦ）在人肝癌组织中的表达及微血管密度（ＭＶＤ）的病理意义。方法 对３０例人肝细胞肝癌９ＨＣＣ）及相应癌旁组织,１０例肝硬化,５例轻度慢性肝炎和４例正常肝组织,进行了ＣＤ３４、ＶＥＧＦ免疫组织化学ＳＰ法检测,对ＣＤ３４阳性血管进行ＭＶＤ计数,对ＶＥＧＦ进行半定量计数,并结合肝癌的病理特征进行分析。结果 ＨＣＣ组织中ＣＤ３４呈广泛,窦隙状阳性表达,而在正常及     

OSAHS患者腭咽组织血管内皮生长因子水平与微血管密度相关性分析

目的 探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者腭咽组织中血管内皮生长因子(VEGF)水平与微血管密度(MVD)的相关性.方法 选择经多导睡眠监测仪(PSG)确诊的40例OSAHS患者组织标本(其中轻度7例,中度12例,重度21例),其中男性36例,女性4例;年龄29～62岁.6例无鼾症患者的软腭组织作为对照组,其中男性5例,女性1例;年龄18-58岁.采用苏木精-伊红(HE)染色法染色腭咽部组织,用光学显微镜观察其病理组织学改变,酶联免疫吸附分析检测血浆、腭咽组织匀浆中VEGF的含量,免疫组织化学技术检测MVD的表达情况.结果 酶联免疫吸附分析显示,OSAHS患者血浆及腭咽组织匀浆中VEGF水平均明显高于对照组,差异有显著统计学意义(P＜0.01);中、重度OSA HS组与对照组比较,MVD表达差异均有显著统计学意义(P＜0.01),轻度组与对照组比较差异无统计学意义(P＞0.05);组织匀浆中VEGF水平与MVD呈正相关(P＜0.01).结论 OSAHS患者腭咽部存在新生血管生成,与缺氧程度有关,VEGF在其发生发展过程中可能起到重要作用.     

血管内皮生长因子-D、 微血管密度及微淋巴管密度的表达与乳腺癌临床病理特征的相关性

目的 探讨乳腺癌中血管内皮生长因子D(vascular endothelial growth factor-D,VEGF-D)及微血管密度(microvessel density,MVD)、微淋巴管密度(Lymphatic vessel density,MLD)表达情况及意义.方法 收集2009年1月至2016年5月在临沂市肿瘤医院病理科存档病例,其中乳腺癌61例,乳腺增生症23例.采用免疫组化法检测各组织VEGF-D、MVD和MLD表达.结果 乳腺癌组织中VEGF-D蛋白阳性率为62.30%,明显高于乳腺增生组织,差异有统计学意义(χ2=16.215,P<0.05);乳腺癌组织中MVD和MLD分别为(17.70±7.10)和(2.41±0.85),明显高于乳腺增生组织,差异有统计学意义(t=10.900、t=8.795,P<0.05);VEGF-D表达与乳腺癌患者年龄、肿瘤大小以及淋巴结转移无明显关系(χ2=0.394、0.032、0.244,P>0.05);MVD和MLD密度与乳腺癌患者年龄和肿瘤大小无明显差异(χ2=0.081,0.126,0.219,0.196,P>0.05);VEGF-D、MVD和MLD密度与乳腺癌组织学分级相关(χ2=13.076、23.892、10.082,P<0.05),随着组织学分级递增,VEGF-D、MVD和MLD密度明显增高;MVD和MLD在乳腺癌伴淋巴结转移中密度明显高于无淋巴结转移(t=2.481、5.791,P<0.05).结论 VEGF-D在乳腺癌组织中呈高表达,可能在乳腺癌的发生发展中起重要作用,而MVD和MLD与乳腺癌肿瘤分化、转移有一定的关系.     

血管内皮生长因子C和nm23表达与微血管密度及宫颈癌转移的关系

目的探讨血管内皮生长因子-C(vascular endothelial growth factor-C,VEGF-C)和nm23(non-metastasis23)表达与微血管密度(microvessel density,MVD)及宫颈癌转移的关系。方法采用免疫组化SABC法检测16例正常宫颈上皮及68例宫颈癌中VEGF-C、nm23的表达。并用CD105标记新生血管内皮细胞,计算肿瘤内MVD。结果VEGF-C在宫颈癌组织中的阳性表达率显著高于正常组织(P<0.01),淋巴结转移组VEGF-C阳性率高于无淋巴结转移组(P<0.05),VEGF-C表达强度与MVD呈正相关(P<0.05)。nm23蛋白表达率显著低于正常组织(P<0.01),淋巴结转移组nm23阳性率低于无淋巴结转移组(P<0.05)。nm23在宫颈癌中的表达与VEGF-C呈负相关(P<0.01)。结论宫颈癌组织VEGF-C呈高表达、nm23呈低表达,可能在宫颈癌血管生长、肿瘤浸润转移过程中起重要作用。检测宫颈癌中VEGF-C、nm23表达对进一步了解宫颈癌局部血管生成情况及判断预后有一定的应用价值。     

姜黄素对佐剂性关节炎大鼠滑膜血管新生的影响

<正>目的:观察佐剂性关节炎大鼠血清血管内皮生长因子水平,滑膜血管新生和血管内皮生长因子及其受体的表达及姜黄素对其干预作用,探讨姜黄素治疗类风湿关节炎的可能机制。方法:取SD大鼠,制成佐剂性关节炎模型,设正常组、模型组、姜黄素组、甲氨喋呤组。造模后第9天起分别予以腹腔注射姜黄素50mg/     

脑星形细胞肿瘤中PTEN、血管内皮细胞生长因子表达与微血管密度

一、材料和方法 1.材料:人星形细胞肿瘤标本43例(患者中男28,女15)取自南通医学院附属医院病理科1987～2000年存档的手术标本。患者年龄14～69岁,平均年龄40.4岁,按WHO胶质瘤分级标准,Ⅰ级3例(均为毛细胞型),Ⅱ级18例(原浆型14例,纤维型4例),Ⅲ级12例(肥胖型3例,间变型9例)Ⅳ级10例(为胶质母细胞瘤),均经病理诊断证实为星形细胞肿瘤。即用型兔抗人PTEN、第Ⅷ因子相关抗原(FⅧ     

CD147分子通过VEGF促进类风湿关节炎滑膜组织中的血管新生

目的观察类风湿关节炎(RA)滑膜组织中CD147表达强度与血管内皮生长因子(VEGF)表达水平间的相关性,并探讨成纤维样滑膜细胞(FLS)表面CD147的水平变化对VEGF表达的影响。方法收集15例RA患者滑膜,以4例骨关节炎(OA)患者滑膜作对照,采用免疫组织化学SP染色方法检测滑膜组织中CD147和VEGF的表达;体外原代培养FLS细胞,分别加入CD147抗体,PI3K通路阻断剂,MAPK通路的ERK1/2、P38及JNK阻断剂等作用FLS细胞,ELISA检测细胞培养上清中VEGF的表达水平。结果与4例OA滑膜组织CD147和VEGF表达相比,15例RA滑膜组织中均有CD147、VEGF均高表达。其中,表达CD147的细胞主要为成纤维样滑膜细胞、单核-巨噬细胞和淋巴细胞;表达VEGF的细胞主要为成纤维样滑膜细胞、微血管周围成纤维样细胞及血管平滑肌细胞。滑膜组织中CD147和VEGF的表达强度间具有统计学意义。ELISA结果显示,在使用LY294002或抗HAb18GmAb阻断CD147表达后,VEGF的表达量显著下降(P<0.05);而MAPK阻断剂(PD98059、SP600125和SB203580)等对VEGF表达水平无统计学意义(P>0.05)。结论CD147经PI3K-Akt信号通路在RA滑膜组织中上调VEGF促进血管新生。提示CD147在RA血管新生和血管翳形成中有重要意义。     

Expression of vascular endothelial growth factor by synovial fluid neutrophils in rheumatoid arthritis (RA)

Most of the leucocytes infiltrating rheumatoid synovial fluid (SF) are neutrophils capable of producing a variety of inflammatory mediators known to contribute significantly to the disease process during active RA. In the present study, we investigated the contribution made by SF neutrophils to the elevated levels of vascular endothelial growth factor (VEGF) seen in rheumatoid SF. Rheumatoid SF neutrophils were found to contain significantly larger amounts of both VEGF protein and its mRNA than peripheral blood neutrophils from either RA patients or healthy controls. Levels of cell-associated VEGF were well correlated with free VEGF in SF, which was significantly higher than in SF from osteoarthritis patients. Levels of SF neutrophil-associated VEGF also correlated with RA disease activity and cell surface integrin expression. Thus, SF neutrophil-associated VEGF may be considered an indicator of both local and systemic inflammation of RA, contributing to the neovascularization seen during RA synovitis.     

Placenta growth factor (PlGF) induces vascular endothelial growth factor (VEGF) secretion from mononuclear cells and is co-expressed with VEGF in synovial fluid

The aims of this study were (i) to determine whether PlGF, VEGF and PlGF/VEGF heterodimers are detected in synovial fluid (SF) and plasma samples from patients with a range of arthropathies; (ii) to describe whether any correlation exists between SF PlGF, VEGF and PlGF/VEGF heterodimer levels and the total and differential SF leucocyte counts; and (iii) to investigate the regulation of peripheral blood mononuclear cell (PBMC) VEGF secretion by stimuli relevant to inflammatory joints. PlGF, VEGF and PlGF/VEGF heterodimer levels were measured in the SF and plasma of patients with a range of arthropathies and normal controls by ELISA. Western blotting for PlGF was performed on SF from three patients with rheumatoid arthritis (RA) and primary inflammatory arthropathies. VEGF was quantified in cell culture supernatants after stimulation with lipopolysaccharide (LPS), PlGF or cobalt ions of PBMC isolated from RA patients and controls. PlGF and VEGF were detected in all SF samples. PlGF/VEGF heterodimers were detected in 10.2% of SF samples, most frequently in RA samples. Western blotting confirmed the presence of PlGF in RA SF. PlGF was detected in 52% of RA and 31% of control plasma samples, and VEGF was detected in 38% of RA and 38% of control plasma samples. PlGF/VEGF heterodimers were detected in 21% of RA samples and none of the control samples. In primary inflammatory arthropathy patients, SF PlGF and VEGF levels correlated significantly with the SF total leucocyte count and the neutrophil count. PlGF was the most potent inducer of PBMC VEGF production in both RA and control subjects. This is the first report of the detection of PlGF and PlGF/VEGF heterodimers in the SF of patients with inflammatory arthropathies, and we have shown for the first time that PlGF up-regulates PBMC VEGF production. PlGF may therefore play a key role in the production of VEGF in the inflammatory joint.     

Identification of the major fibroblast growth factors released spontaneously in inflammatory arthritis as platelet derived growth factor and tumour necrosis factor-alpha.

Rheumatoid arthritis is characterized by chronic inflammation and proliferation of a number of important elements within the joint including the synovial fibroblasts. Elevated levels of a number of cytokines such as Il-1, IL-2, IL-6, interferon-gamma (IFN-gamma), transforming growth factor-beta and tumour necrosis factor-alpha (TNF-alpha) have been detected in the synovial fluid of patients with rheumatoid arthritis and other inflammatory arthritides. It seems likely that local release of such mediators may be responsible for the proliferation and overgrowth of connective tissue elements in these disorders. In order to ascertain whether there was evidence to suggest local production or release of fibroblast growth factors in the joint in inflammatory arthritis, and to determine their identity, cells were obtained from the synovial fluid of 15 patients with chronic inflammatory arthritides. All subjects' synovial fluid cells spontaneously released growth factor activity for fibroblasts. This was present in large amounts, being detectable in culture supernatants diluted to a titre of at least 1/625. By a series of depletion experiments using solid-phase bound antibodies to cytokines, it was possible to demonstrate that this activity was due to TNF-alpha and platelet-derived growth factor (PDGF). Thus, this study showed for the first time that functionally active PDGF was released from synovial fluid cells. Both PDGF and TNF-alpha appeared to contribute in approximately equal amounts to this fibroblast growth factor activity, and were synergistic in effect. Thus this study provides evidence for the local production and release of these two cytokines and suggests that together they are the dominant factors in fibroblast proliferation within the synovial cavity.     

Characteristics of synovial fluid effusion in collagen-induced arthritis (CIA) in the DA rat; a comparison of histology and antibody reactivities in an experimental chronic arthritis model and rheumatoid arthritis (RA)

We have characterized the cellular content and some antibody reactivities in synovial fluid (SF) from DA rats with CIA. Since CIA is widely used as a model for RA, in which many studies concerning immune responses are performed on SF samples, we considered it important to describe the local, disease-causing immune reactions in CIA. At the peak of disease (day 22 after immunization), the major cell population in CIA SF was granulocytes (72%), but macrophages (17.9%), plasma cells (2.6%) and lymphocytes (7.7%) were also present. The CIA synovial membrane (SM) obtained at the same time was mainly infiltrated by monocytes, with granulocytes, lymphocytes and plasma cells also present. Cell populations in blood did not differ between arthritic and normal DA rats. Equally, high anti-collagen type II (CII) and rheumatoid factor (RF) levels could be detected both in SF and in sera. Notably, RF levels were also increased in normal DA rats. Moderate levels of anti-heat shock protein 65 kD (hsp) antibodies were recorded systemically in both normal and diseased animals. In conclusion, the cellular composition in SF and in SM are similar in rat CIA and in RA. The morphological differences between SF and SM that are characteristic for RA could also be demonstrated in CIA. The antibody data indicate systemic production of anti-CII and anti-hsp antibodies as well as RF, but they give no support for local production of these antibodies in the joints, which is the case in RA.     

兔VX2肝癌超声造影定量指标与肿瘤微血管密度及血管内皮生长因子的相关性分析

目的研究肝癌超声造影定量指标与肿瘤微血管密度（MVD）及血管内皮生长因子（VEGF）的相关性。方法25只VX2成年兔肝癌模型,兔龄3个月,体质量（2．9±0．1）kg。行超声造影检查,利用Qkab软件对造影动态图像进行时间-强度分析,得出肝癌组织与周边正常肝组织曲线增强上升斜率（AS）、开始增强时间（AT）、达峰时间（TTP）、峰值强度（PI）、曲线下面积（AUC）及相对参数,造影后对标本做MVD和VEGF检测,分析超声造影各定量指标与肝癌组织内部MVD及VEGF的相关性。结果在超声造影定量指标中,肝癌组织的AT、TTP及PI与周边正常肝组织相比[（7．29±0．73）svs（10．15±0．44）s,（10．02±0．73）s vs（17．01±0．81）S,24．24±4．29YS16．83±1．511,差异有显著统计学意义（P〈0．01）。肝癌组织的各项定量指标中,相对TTP与MVD、VEGF呈正相关（r分别为0．517、0．528,P〈0．05）,相对PI与MVD呈正相关（r=0．564,P〈0．01）。MVD与VEGF表达呈正相关,相关系数为0．641（P=0．01）。结论超声造影定量指标可在一定程度上反映肝癌组织内部微血管分布情况。有一定临床实用价值。     

甲状腺癌组织中VEGF和VEGF-C的表达及意义

目的　探讨血管内皮生长因子(VEGF)、VEGF- C在甲状腺癌中的表达及其意义。方法　应用免疫组化S P法检测44例甲状腺癌中VEGF、VEGF C的表达情况,并以17例癌旁正常甲状腺组织作对照。结果　VEGF、VEGF- C在甲状腺癌中呈高水平表达(88. 6%、81. 8% )。VEGF表达随癌组织分化程度的减低而增高, 9例死亡病例均为阳性表达;VEGF- C表达随癌组织分化程度的减低而减低,乳头状癌阳性表达(88 .9% )高于其它类型,VEGF- C阳性率在有淋巴结转移组(92. 0% )明显高于无淋巴结转移组(68. 4% ) (P<0. 05)。9例死亡病例中7例为阳性表达,且7例同时VEGF呈阳性表达。结论　VEGF、VEGF- C表达与甲状腺癌病理分型及预后可能有一定关系,VEGF- C与甲状腺癌淋巴结转移密切相关。