血管内皮生长因子在恶性胸腔积液中的作用

血管内皮生长因子（vascular endothelial growth factor，VEGF）在恶性胸腔积液发生机制中起重要作用，VEGF在胸腔积液中的作用是一个有前途的迅速发展的研究领域，有可能提供胸腔积液形成病理生理学的新视点。阻断VEGF信号传导有可能是恶性胸腔积液治疗的新方向。本文就VEGF在恶性胸腔积液诊断、治疗的进展作一综述。     

血管内皮生长因子与恶性胸腔积液的关系

临床上恶性胸腔积液是肿瘤常见的并发症,多项研究表明血管内皮生长因子(vascular endothelial growth factor,VEGF)在恶性胸腔积液中明显升高,其调控肿瘤的生长、血管的密度和渗透性及肿瘤的转移,从而影响恶性胸腔积液的产生.VEGF通过不同机制调控血管的通透性,还与炎症、凝血等途径相互作用.VEGF联合其他指标可作为辅助诊断及鉴别诊断的依据,同时部分VEGF/VEGFR对恶性胸腔积液有明确疗效.     

血管内皮生长因子及内皮抑素检测对结核性和癌性胸腔积液的诊断价值

研究结果表明,胸腔积液中血管内皮生长因子(VEGF)的检测有助于结核性和癌性胸腔积液的诊断与鉴别[1-2],有关胸腔积液中内皮抑素(endostatin)的研究还很少[3],因此,我们同时检测胸腔积液中VEGF和内皮抑素水平,探讨VEGF和内皮抑素对结核性与癌性胸腔积液的诊断及鉴别诊断.     

血管内皮生长因子、基质金属蛋白酶-2对良恶性胸腔积液的诊断价值

目的探讨胸腔积液中血管内皮生长因子(VEGF)和基质金属蛋白酶-2(MMP-2)水平对恶性胸腔积液及结核性胸腔积液(良性)的鉴别诊断价值。方法采用ELISA法,检测40例恶性胸腔积液、40例结核性胸腔积液病人胸腔积液中VEGF和MMP-2表达水平,并进行比较。结果恶性胸腔积液组VEGF和MMP-2水平均明显高于结核性胸腔积液组,差异有显著性(P<0.01)。良恶性胸腔积液中VEGF和MMP-2表达水平呈正相关。VEGF和MMP-2联合检测可提高敏感性和特异性,分别为:86.5%、95.6%。若VEGF、MMP-2和CEA联合检测其敏感性和特异性分别为:92.1%、100%。结论联合检测胸腔积液VEGF和MMP-2对鉴别结核性和恶性胸腔积液具有重要的临床价值。     

血管内皮生长因子联合基质金属蛋白酶-9对老年人恶性胸腔积液的诊断价值

血管内皮生长因子(vascular endothelial growth factor,VEGF)和基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)均与肿瘤转移有关.有研究显示,VEGF在癌性胸腔积液中高于结核性胸腔积液[1],但对VEGF在胸腔积液中的诊断价值还有争论[2].MMP-9在不同病因的胸腔积液中变异较大[3-5].本研究旨在探讨VEGF联合MMP-9在恶性胸腔积液临床诊断中的价值.     

联合检测血管内皮生长因子、血管生成素-2、癌胚抗原对恶性胸腔积液的诊断价值

目的探讨血管内皮生长因子(VEGF)、血管生成素-2(Ang-2)、癌胚抗原(CEA)联合检测对于恶性胸腔积液的诊断价值。方法选取2011年10月至2014年5月于山西大同大学附属医院呼吸内科住院的胸腔积液患者67例。根据确诊结果,分为恶性胸腔积液35例,良性胸腔积液32例。采用酶联免疫吸附试验检测胸腔积液中VEGF、Ang-2、CEA的含量。结果恶性组胸腔积液中VEGF、Ang-2、CEA含量高于良性胸腔积液,差异具有统计学意义(P0.05)。单独检测VEGF、Ang-2、CEA的AUC(ROC曲线下面积)分别是0.844,0.837,0.905,灵敏度74.3%,77.1%,85.7%,特异度87.5%,81.2%,90.6%。联合检测胸腔积液中VEGF、Ang-2、CEA的AUC,灵敏度和特异度分别为0.990,99.2%和100.0%。结论联合检测胸腔积液中的VEGF、Ang-2、CEA对鉴别良、恶性胸腔积液有较好的临床价值。     

血管内皮生长因子及转化生长因子-β联合检测在老年结核性与恶性胸腔积液中的价值

目的 监测老年结核性胸腔积液和老年恶性胸腔积液中血管内皮生长因子（VEGF）和转化生长因子-β（TGF-β）在鉴别老年结核性和老年恶性胸腔积液中的价值。方法 老年结核性胸腔积液组31例，老年恶性胸腔积液组30例，分别行胸腔闭式引流术。采用酶联免疫吸附法（ELISA）法检测2组患者的胸液中VEGF及TGF-β的水平。结果 恶性胸腔积液中VEGF及TGF-β的水平呈正相关（r=0．438，P〈0．05）。恶性胸腔积液中VEGF及TGF-β水平[（269±62）ng／L，（125．5±12．0）mg／L]较结核性胸腔积液[（104±55）ng／L，（81±23）mg／L]升高，差异有统计学意义（P〈0．05）。结论 VEGF及TGF-β在老年恶性胸腔积液的形成起重要作用，对恶性胸腔积液与结核性胸腔积液的鉴别具有重要价值。     

血管内皮生长因子、肿瘤坏死因子和水溶性上皮细胞钙黏蛋白在鉴别良恶胸腔积液中的临床意义

目的 探讨血管内皮生长因子(VEGF)、肿瘤坏死因子(TNF-α)和水溶性上皮细胞钙黏蛋白(sE-cadherin)在鉴别良恶性胸腔积液中的临床意义.方法 收集2008年6月-2010年8月我院住院患者的胸腔积液80份,应用酶联免疫法分别检测VEGF、TNF-α和sE-cadherin的浓度.结果 3者渗出液的浓度均明显高于漏出液,恶性胸腔积液中VEGF、sE-cadherin的浓度明显高于结核性,而恶性胸腔积液中TNF-α浓度明显低于结核性胸腔积液,两两比较差异均有统计学意义(P＜0.05).结论 VEGF、TNF-α在渗出液中浓度较高,恶性胸腔积液中sE-cadherin明显升高,3者的检测在胸腔积液的鉴别诊断中具有重要的临床意义.     

VEGF、hs-CRP及TNF-α在鉴别肺结核及肺癌胸腔积液的应用价值

目的探讨血管内皮生长因子(VEGF)、超敏C-反应蛋白(hs-CRP)及肿瘤坏死因子-α(TNF-α)在鉴别肺结核及肺癌胸腔积液的应用价值。方法检测52例肺结核患者及50例肺癌患者胸腔积液的VEGF、hs-CRP及TNF-α水平。结果与肺癌患者相比,肺结核患者胸腔积液的VEGF水平降低,而hs-CRP及TNF-α水平显著升高(P<0.05);VEGF、hs-CRP及TNF-α三者联合检测诊断恶性胸腔积液的敏感性显著提高,敏感度与特异度分别为88.0%和82.7%。结论胸腔积液VEGF、hs-CRP及TNF-α的检测可作为鉴别肺结核及肺癌患者的临床参考指标,三者的联合检测可显著提高诊断的敏感性。     

端粒酶血管内皮生长因子粘附分子基质金属蛋白酶检测对胸腔积液性质鉴别的临床意义

目的 通过对良恶性胸腔积液中端粒酶、血管内皮生长因子(VEGF)、粘附分子(CD44V6)、基质金属蛋白酶(MMP2、MMP9)单项和联合检测,探讨它们在胸腔积液性质鉴别诊断中的价值.方法 选取2004年9月至2005年6月浙江省舟山市人民医院60例胸腔积液患者,其中30例为恶性胸腔积液,30例为良性胸腔积液.抽取胸腔积液后采用反转录-聚合酶链反应(RT-PCR)及酶联免疫吸附试验(ELISA)方法进行端粒酶、VEGF、CD44V6、MMP2、MMP9检测,计算出单项和联合检测的敏感性、特异性.结果 在单项检测指标中,VEGF的诊断效能最好,其诊断分界点为181.1μg/L,敏感性为90.0%,特异性为86.7%.联合检测中,以(VEGF+CD44V6)和(VEGF+MMP2)的诊断效能较好.VEGF+CD44V6联合检测的敏感性为83.3%,特异性为90.0%.VEGF+MMP2联合检测的敏感性为80.0%,特异性93.3%.结论 恶性胸腔积液中的端粒酶、VEGF、CD44V6、MMP2、MMP9水平明显高于良性胸腔积液,差异有统计学意义.单项检测中VEGF对于恶性胸腔积液的诊断有较高的敏感性和特异性;联合检测则以VEGF+CD44V6和VEGF+MMP2的敏感性和特异性为最高.     

肺癌患者胸水中VEGF含量的测定及临床意义

目的探讨肺癌患者胸水中VEGF含量的测定及临床意义。方法选择于我院就诊治疗的70例胸水患者,观察两组患者胸水中VEGF含量的差异情况及阳性表达情况和临床病理特征的联系。结果恶性肿瘤患者胸水中VEGF的含量明显高于良性胸水VEGF的含量;胸液中VEGF含量用以诊断恶性胸水的最佳界值为1732.65 pg/ml;恶性胸水中VEGF阳性表达率为86.11%,高于良性胸水26.47%(χ2=25.40,P0.05);VEGF含量在肺癌的各种临床病理状态下,无显著性差异(P0.05)。结论肺癌患者胸水中VEGF含量的测定具有一定的临床诊断价值,对良、恶性胸水患者具有鉴别诊断意义。     

Vascular endothelial growth factor: the key mediator in pleural effusion formation

Pleural effusion is common in clinical practice. Increased vascular permeability and leakage play a principal role in the development of exudative pleural effusions. In vitro and in vivo evidence have solidly established vascular endothelial growth factor (VEGF), a potent inducer of vascular permeability, as a crucial mediator in pleural fluid formation. VEGF is present in high quantities in human effusions. In the pleural space, mesothelial cells, infiltrating inflammatory cells, and (in malignant pleuritis) cancer cells contribute to the VEGF accumulation in the pleural fluids. Pleural fluid VEGF is biologically active and may promote tumor growth and chemotaxis. Strategies to antagonize the VEGF activity at various target points of its signaling pathway have shown success in vitro and in animal models of malignant pleural or peritoneal effusions. Novel agents targeting VEGF activities are undergoing clinical trials. Regulation of VEGF activity and vascular permeability represent a rapidly expanding field of research, which is likely to provide further insight in the pathophysiology of pleural fluid formation.     

VEGF在胸腔积液病因鉴别诊断中的临床应用

目的探讨VEGF在胸腔积液病因鉴别诊断中的临床应用价值。方法观察我院100例并发胸腔积液患者,均明确引起胸腔积液病因,检测胸腔积液中VEGF水平。结果对比恶性肿瘤组和对照组的胸腔积液VEGF水平,恶性肿瘤组(387±98.05 ng/L)较对照组(102±65.24 ng/L)高,存在显著差异,具有统计学意义。结论胸腔积液VEGF检测简单易行,通过其水平的高低,可以在分析胸腔积液病因时籍此指导鉴别诊断。     

Vascular endothelial growth factor in pleural fluid.

STUDY OBJECTIVES: The purpose of this study was to analyze the relationship of the pleural fluid vascular endothelial growth factor (VEGF) level with the diagnostic category and with the pleural fluid characteristics in a group of 70 patients. DESIGN: The VEGF levels of consecutive patients undergoing therapeutic thoracentesis were determined with an enzyme-linked immunosorbent assay. SETTING: University-affiliated tertiary care center. RESULTS: The median level of pleural fluid VEGF in the patients with congestive heart failure (150 pg/mL) was significantly (p < 0.05) lower than the median level in the patients with coronary artery bypass grafting (357 pg/mL), which in turn was significantly lower (p < 0.05) than the median levels in the patients with malignancy (1,097 pg/mL). The overlap between groups, however, limits the diagnostic usefulness of pleural fluid VEGF levels. The VEGF level was most closely correlated with the lactate dehydrogenase level (r = 0.42, p < 0.001) and was also significantly correlated with the total pleural fluid protein level. The median VEGF levels in the pleural fluid of patients with breast cancer were significantly lower (p = 0.017) than in those with lung cancer. The VEGF level was very high (3,294 pg/mL) in the one patient with pulmonary embolism. CONCLUSIONS: We conclude that the VEGF levels in pleural fluid differ significantly from one diagnostic category to another with the highest median levels occurring in patients with malignant pleural effusions. We speculate that VEGF may be responsible for the pleural fluid accumulation in at least some situations.     

结核性和恶性胸膜炎患者VEGF的水平及意义

目的 通过检测结核性胸膜炎及恶性胸膜炎患者血清和胸水中血管内皮生长因子（VEGF）含量,分析VEGF在两组患者血清、胸水中的差异,探讨VEGF在二者中的意义和诊断价值.方法 对确诊结核性胸膜炎和恶性胸膜炎各30例的患者在同一日留取胸水标本10 ml及静脉血5 ml,采用双抗体夹心酶联免疫吸附试验检测患者胸水及血清中VEGF水平,分析其差异及相关性.结果 结核组血清和胸水VEGF检测值分别为（45.33±18.33） ng/L、（62.73±24.65） ng/L;恶性组血清和胸水VEGF检测值分别为（66.00±29.83） ng/L、（95.54±42.11） ng/L;恶性组血清及胸水中VEGF含量均高于结核组（t值分别为3.9、5.2,P值均＜0.05）.VEGF在两组的血清和胸水中均呈正相关性（r值分别为0.53、0.38,P值均＜0.05）.结论 在结核性胸膜炎及恶性胸膜炎患者血清、胸水中VEGF水平有差异,恶性高于结核性;两组患者胸水中VEGF含量均高于血清,胸水VEGF含量随着血清VEGF含量增高而增高.检测胸腔积液患者血清和胸水中VEGF含量对结核性胸膜炎和恶性胸膜炎的诊断和鉴别诊断有一定的价值.     

Vasoactive mediators (VEGF and TNF-alpha) in patients with malignant and tuberculous pleural effusions

OBJECTIVE: Vascular endothelial growth factor (VEGF) is a potent endothelial cell-specific mitogen that promotes angiogenesis, vascular hyperpermeability, and vasodilatation by autocrine mechanisms involving nitric oxide (NO). This study was undertaken to determine the potential role of VEGF in the pathogenesis of pleural effusions, and its relationship with tumour necrosis factor (TNF)-alpha and NO in the pleural fluid and serum of patients with tuberculous and malignant pleural effusions. METHODOLOGY: Pleural fluid and serum (SE) VEGF, TNF-alpha and NO levels were measured in 30 patients with exudative pleural effusion (15 with malignancies and 15 with tuberculosis). Control pleural fluid was obtained from 10 patients with transudative pleural effusion due to congestive heart failure and control serum samples were obtained from 10 healthy individuals. VEGF and TNF-alpha were measured by enzyme-linked immunosorbent assay and NO by a colorimetric method. Pleural biopsy, cytology or microbiological methods were used to make the final diagnosis. RESULTS: In patients with exudative pleural effusions, the mean pleural fluid and serum VEGF levels and their ratios (P < 0.0001 for all) and TNF-alpha levels (P < 0.01, P < 0.0001 and P < 0.05) were significantly elevated compared to those with transudative pleural effusion. In malignant effusions, pleural fluid and serum VEGF levels were significantly elevated (P < 0.001 and P < 0.0001) while pleural fluid, and serum levels and their ratios of TNF-alpha (P < 0.001, P < 0.01 and P < 0.05) were significantly lower than those in tuberculosis. NO levels did not distinguish between tuberculous and malignant effusions. CONCLUSIONS: In patients with malignant pleural effusions, levels of VEGF were significantly higher, while levels of TNF-alpha were significantly lower, than in patients with tuberculous effusions. In malignant pleural effusions, the elevated pleural fluid levels of VEGF and TNF-alpha are noteworthy. Our data support the hypothesis that blockade of VEGF, might benefit cancer patients with recurrent ascites or pleural fluid accumulation.     

IFN-γ、VEGF联合检测在结核性胸腔积液和恶性胸腔积液鉴别诊断中的价值

目的探讨γ-干扰素(IFN-γ)、血管内皮生长因子(VEGF)联合检测在结核性胸腔积液(胸液)和恶性胸液鉴别诊断中的价值。方法以2004年3月—2005年5月住院的87例胸腔积液患者为研究对象,其中结核性胸液45例,恶性胸液42例,应用酶速率法检测胸液中腺苷酸脱氨酶(ADA)的活性,应用ELISA法检测IFN-γ、癌胚抗原(CEA)和VEGF的浓度。应用受试者工作特征曲线(receiver operating characteristic curve,ROC)计算上述指标及VEGF/IFN-γ比值的诊断敏感性、特异性和准确性。结果结核性胸液组ADA和IFN-γ含量高于恶性胸液组,有显著性差异(P<0.01);恶性胸液组CEA、VEGF含量和VEGF/IFN-γ比值高于结核性胸液组,有显著性差异(P<0.01)。IFN-γ对结核性胸液诊断的敏感性和特异性高于ADA;VEGF/IFN-γ比值对恶性胸液诊断的敏感性和特异性高于CEA和VEGF。结论IFN-γ和VEGF/IFN-γ比值可以作为临床上鉴别结核性胸液和恶性胸液的有效指标。     

Vascular endothelial growth factor and proinflammatory cytokines in pleural effusions

To evaluate the predictive value of vascular endothelial growth factor (VEGF) in the differential diagnosis of pleuritis and its association with other proinflammatory cytokines in pleural effusion, we measured VEGF together with interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha) and soluble intercellular adhesion molecule-1 (sICAM-1) in pleural effusions. We investigated 127 patients with pleural effusion (congestive heart failure: 21; parapneumonic: 27; tuberculous: 41; malignant: 38). We examined standard parameters of pleural effusion and measured pleural effusion VEGF, IL-1beta, TNF-alpha and sICAM-1 using enzyme-linked immunosorbent assay. VEGF level was significantly higher in malignant effusion than in other groups. TNF-alpha level was significantly higher in tuberculous pleurisy than in other groups. In tuberculous pleurisy VEGF level showed significant positive correlations with mononuclear cell counts and all investigated cytokines. The sensitivity and specificity of VEGF in the diagnosis of malignancy was 100 and 84%, respectively (cutoff = 2000 pg/ml). The sensitivity and specificity of VEGF and TNF-alpha in the diagnosis of tuberculous pleurisy (VEGF titer <2000 pg/ml and TNF-alpha titer > 55 pg/ml) was 88.9 and 77.1%, respectively. We propose that measurement of VEGF together with TNF-alpha is helpful in differentiating between tuberculous pleurisy and malignant pleural effusion and that VEGF correlates with proinflammatory cytokines especially in tuberculous pleurisy. We also propose that measurement of pleural VEGF is helpful for the diagnosis of malignant pleural effusion.     

血管内皮生长因子、细胞角蛋白19片段鉴别良恶性胸腔积液的临床价值

目的探讨联合检测血清和胸腔积液中血管内皮生长因子、细胞角蛋白19片段对鉴别结核性与肺癌性胸腔积液的临床价值。方法分别采用双抗体夹心酶联免疫吸附和电化学发光免疫法检测肺癌性和结核性胸腔积液患者血清和胸腔积液中血管内皮生长因子及细胞角蛋白19片段的表达水平。结果肺癌性胸腔积液患者血清和胸腔积液中血管内皮生长因子及细胞角蛋白19片段的表达水平比较有统计学意义（P〈0．01）,联合检测可使敏感性提高至92．00％,特异性提高至86．84％。结论联合检测胸腔积液和血清中血管内皮生长因子、细胞角蛋白19片段,对鉴别肺癌性与结核性胸腔积液具有重要的临床价值。