非小细胞肺癌组织中VEGF、PEDF的表达变化及意义

目的 观察非小细胞肺癌组织中血管内皮生长因子（VEGF）与色素上皮衍生因子（PEDF）的表达变化,并探讨其意义.方法 采用免疫组化法对50例非小细胞肺癌组织中的VEGF、PEDF进行检测,以CD31标记免疫组化法检测微血管密度（MVD）.结果 VEGF、PEDF在肺癌组织中的阳性表达率分别为64%、44%,二者的表达呈负相关（r=-0.599,P＜0.01）.MVD值在PEDF阴性组高于阳性组（P＜0.05）,在VEGF阳性组则高于阴性组（P＜0.05）.VEGF和PEDF的表达与肺癌远处转移、分化程度、临床分期有关（P均＜0.05）.结论 在非小细胞肺癌组织中VEGF、PEDF的表达有相关性,且与MVD关系密切,PEDF可能通过抑制MVD生成而起抑癌作用;检测VEGF和PEDF有助于肺癌远处转移、分化程度、临床分期的判断.     

CT灌注成像预测吉非替尼治疗非小细胞肺癌的敏感性

目的探讨非小细胞肺癌(NSCLC)患者CT灌注成像(CTP)参数特点对吉非替尼疗效的预测价值。方法回顾性分析29例经病理证实的晚期NSCLC患者应用吉非替尼治疗前的CT容积灌注资料及临床资料,根据RECIST标准将患者分为缓解组和未缓解组,对比分析两组治疗前病灶CT容积灌注参数。结果缓解组19例患者,未缓解组10例患者,缓解组血容量(BV)值、血流量(BF)值、表面通透性(PS)值高于未缓解组,缓解组肿瘤组织的对比剂平均通过时间(MTT)较未缓解组缩短(P<0.05)。结论 CTP可以量化反映肿瘤微血管的代谢功能,可以为预测吉非替尼治疗NSCLC的疗效提供参考。     

非小细胞肺癌组织中VEGF表达的Meta分析

目的探讨血管内皮生长因子(VEGF)的表达与非小细胞肺癌的关系。方法计算机检索Cochrane、PubMed、CNKI等数据库,辅以手工检索,收集2005年至今的相关文献,按照纳入与排除标准选择独立病例对照研究,最终纳入文献9篇,非小细胞肺癌807例(NSCLC组),对照组305例,应用Rev-Man5.1分析软件进行Meta分析。结果 VEGF在NSCLC组中的表达水平高于对照组(P<0.01);VEGF表达与非小细胞肺癌分化程度、淋巴结转移、TNM分期有关(P均<0.01),但与其病理分型及患者年龄、性别无关(P均>0.05)。结论 VEGF的表达水平是评估非小细胞肺癌生物学行为的重要指标,可作为抗血管生成靶向治疗过程中指导治疗、疗效判断及监测病情的生物标记物。     

Twist蛋白在非小细胞肺癌中的表达水平及其与VEGF的关系

目的 探讨转录调节因子Twist在非小细胞肺癌(NSCLC)中的表达水平及其与血管内皮生长因子(VEGF)关系.方法 采用链霉素抗生物素蛋白-过氧化物酶(SP)免疫组织化学方法检测50例NSCLC及15例癌旁正常肺组织中Twist蛋白、VEGF的表达,并分析两者与临床病理特征的关系.结果 NSCLC组织中Twist阳性率44%,明显高于癌旁正常肺组织,其表达与肿瘤分化程度有关.VEGF在肺癌、癌旁正常肺组织中的阳性率分别为50%和26.67% (P ＜0.05),其表达与肿瘤分化程度、TNM分期及淋巴结转移有关.Twist蛋白与VEGF的表达之间存在显著正相关(r=0.560 2,P＜0.01).结论 在NSCLC中Twist蛋白、VEGF表达明显增高,其表达与肿瘤分化、分期有关.NSCLC组织中Twist与VEGF表达的上调对肿瘤的发生、发展起着重要作用.     

肺CT灌注成像与非小细胞肺癌患者肿瘤恶性分子表达水平的相关性

目的探讨肺CT灌注成像与非小细胞肺癌(NSCLC)患者肿瘤恶性分子表达水平的相关性。方法 64例NSCLC患者为研究组,另选取同期64例肺良性疾病患者为对照组。两组均行肺CT灌注成像检查,并通过免疫组化法测定肺组织微管相关蛋白轻链(MAPLC)3、自噬基因(Beclin)1、增殖细胞核抗原(PCNA)、CD44v6、钙依赖黏附蛋白(E-cad)和干细胞转录因子(OCT4);以酶联免疫吸附法测定血清血管内皮生长因子(VEGF)、色素上皮衍生因子(PEDF)和DNA甲基化转移酶(DNMT)1水平;以酶联免疫吸附法测定胸膜腔冲洗液醛缩酶(ALDO)A、甲状腺转录因子(TTF)-1和Napsin A水平,分析不同预后患者肺CT灌注成像参数值与肿瘤恶性分子表达水平的相关联。结果研究组Ⅰ期血容量(BV)值与表面通适性(PS)值显著高于对照组,Ⅱ期BV值与PS值显著高于Ⅰ期,Ⅲ期BV值与PS值显著高于Ⅱ期,Ⅳ期BV值与PS值显著高于Ⅲ期(均P<0.05)。研究组未复发56例,复发8例,复发组PS值及BV值显著高于未复发组(均P<0.05)。研究组MAPLC3、Beclin1、E-cad阳性率及血清PEDF、DNMT1水平显著低于对照组,PCNA、CD44v6、OCT4阳性率、血清VEGF、胸膜腔冲洗液ALDOA、TTF-1、Napsin A水平显著高于对照组(P<0.05)。BV值、PS值均和ALODA、TTF-1、Napsin A、VEGF、PCNA、CD44v6、OCT4水平呈正相关(P<0.05),与PEDF、DNMT1、MAPLC3、Beclin1、E-cad呈负相关(P<0.05)。结论肺CT灌注成像参数与NSCLC患者肿瘤恶性分子表达水平相关,可为肿瘤分期、预后评估提供参考。     

非小细胞肺癌患者血清血管内皮生长因子和一氧化氮的水平及临床意义

目的 研究非小细胞肺癌(NSCLC)患者血清血管内皮生长因子(VEGF)和一氧化氮(NO)水平的变化及其与临床分期和病理类型的关系.方法 NSCLC患者40例,对照组50例,采用酶联免疫吸附试验( ELISA)检测血清VEGF和NO的水平.结果 NSCLC组血清VEGF和NO水平显著高于对照组(P＜0.01);NSCLC组血清VEGF和NO两者之间呈明显正相关;NSCLC患者血清VEGF和NO水平随临床分期的递增而逐步升高,不同分期间比较VEGF和NO水平比较差异有统计学意义(P＜0.05);不同病理类型的NSCLC患者血清的VEGF和NO水平比较差异无统计学意义(P＞0.05).结论 NSCLC患者的血清VEGF和NO表达水平对其临床分期和预后有重要意义.     

肝癌组织中PEDF、VEGF的表达及意义

目的探讨色素衍生上皮因子（PEDF）、血管内皮生长因子（VEGF）在肝癌发生、发展中的作用。方法采用免疫组化法检测72份肝癌组织标本中PEDF、VEGF的表达,用CD31标记免疫组化法检测微血管密度（MVD）。结果PEDF、VEGF在肝癌组织中的阳性率分别为41．67％（30／72）、83．33％（60／72）;MVD值PEDF阴性者高于阳性者、VEGF阳性者高于阴性者;PEDF、VEGF表达均与术后复发、肝外转移、临床分期、门静脉癌栓有关;两者表达呈负相关。结论PEDF、VEGF在血管生成过程中具有拮抗作用;PEDF可能通过抑制MVD生成起抑癌作用。     

TFPI-2、VEGF在非小细胞肺癌中的表达及相关性研究

目的研究组织因子途径抑制物-2(tissue factor pathway inhibitor-2,TFPI-2)、血管内皮生长因子(vascular endotheli-al growth factor,VEGF)在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达及其间的相关性。方法采用免疫组化法检测60例NSCLC组织TFPI-2、VEGF的表达及CD31单克隆抗体标记的微血管密度(MVD)。结果 NSCLC中临床分期为Ⅰ、Ⅱ、Ⅲ期的患者中TFPI-2表达阳性率分别为75.8%、25.0%和40.0%(P=0.003),无淋巴结转移和有淋巴结转移的患者中TF-PI-2表达阳性率分别为66.7%、38.1%(P=0.033)。临床分期为Ⅰ、Ⅱ、Ⅲ期的患者中EVGF表达阳性率分别为60.6%、88.3%和93.3%(P=0.040),无淋巴结转移和有淋巴结转移的患者中VEGF表达阳性率分别为64.1%、90.5%(P=0.028)。NSCLC组织中的TFPI-2的表达与VEGF的表达呈负相关(r=-0.351),差异有统计学意义(P=0.004)。高、低MVD组中的TFPI-2阳性表达率分别为41.2%、76.9%(P=0.006)。高、低MVD组中的VEGF阳性表达率分别为76.5%、30.87%(P=0.000)。结论 NSCLC中TFPI-2可能通过下调VEGF的表达抑制肿瘤新生血管的形成,从而抑制NSCLC的生长、浸润及转移。     

PEDF对人肾小球系膜细胞VEGF表达及活性氧簇产生的影响

观察不同浓度高糖培养下及人重组色素上皮衍生因子(PEDF)干预后人肾小球系膜细胞活性氧簇水平、血管内皮生长因子(VEGF)mRNA和蛋白的改变.结果 显示活性氧簇水平、VEGF mRNA和蛋白的表达随糖浓度的升高而增加;PEDF干预后,高糖环境下活性氧簇水平及VEGF的表达明显下降,且呈浓度依赖性.提示PEDF可能通过改善血管通透性和抑制氧化应激延缓糖尿病肾病的进展.     

血清VEGF和p53抗体与非小细胞肺癌的相关性研究

目的分析非小细胞肺癌（NSCLC）患者血清VEGF、p53抗体表达水平及其诊断价值。方法采用酶联免疫吸附法（ELISA）检测69例初诊为NSCLC的患者血清VEGF和p53抗体浓度,另有45例健康志愿者作为对照。结果 NSCLC患者血清VEFG和p53抗体均明显高于对照组健康人群（P〈0.001）,两者在病理分型中腺癌最高（P〈0.001）,临床分期中以Ⅳ期最高（P〈0.001）;VEGF与p53抗体浓度值呈正相关（r=0.762,P〈0.001）;两项联合检测全部NSCLC的敏感性为86.9%,高于单项检测（P〈0.001）。结论 NSCLC患者血清VEFG和p53抗体显著增高,检测患者血清这两项指标对于肺癌的临床辅助诊断有着重要意义。     

Clinical significance of vascular endothelial growth factor in patients with primary lung cancer

OBJECTIVE: Vascular endothelial growth factor (VEGF) is an angiogenesis factor closely associated with the growth and metastasis of malignant tumours. METHODOLOGY: In the present study, we measured plasma VEGF levels in 20 normal subjects (N), 35 patients with benign lung diseases (B), 28 patients with untreated advanced lung cancer (NT) and 10 patients with treated lung cancer (T). In addition, we measured the VEGF levels in pleural effusions from five patients with primary lung cancer and two patients with active infectious diseases. Vascular endothelial growth factor was measured by ELISA. RESULTS: The mean (+/-SD) plasma VEGF level in NT patients (160.8 +/- 177.4 pg/mL) was fivefold higher than that in other patient groups (T, 17.7 +/- 4.9 pg/mL; B, 28.3 +/- 17.6 pg/mL) and the N group (14.9 +/- 7.0 pg/mL; P < 0.01). Vascular endothelial growth factor from lung cancer pleural effusions (17 526.0 +/- 22 498.2 pg/mL) was 25-fold higher than that from patients with active infectious diseases (665.5 +/- 259.0 pg/mL). CONCLUSIONS: Plasma VEGF may be a good clinical indicator for the assessment of primary lung cancer and pleural effusion VEGF in primary lung cancer is higher than pleural effusion VEGF in patients with inflammatory diseases.     

VEGF表达及其与非小细胞肺癌转移、预后关系的研究

目的　探讨血管内皮生长因子 (VEGF)在非小细胞肺癌 (NSCL C)组织中的表达及其与转移、预后的关系。方法　应用免疫组织化学 (S- P)法检测 96例肺癌组织、 31例癌旁组织及 2 0例肺良性瘤样组织的VEGF表达水平 ,并对其与临床、病理特征的关系进行分析。结果　肺癌、癌旁及肺良性瘤样病变组织中 VEGF阳性表达率分别为 72 .9%、 4 5 .2 %和 2 5 % ,三者之间具有显著性差异 (P <0 .0 5 ) ;VEGF在肺癌组织中的表达与患者的年龄、性别、吸烟、临床分期、分化程度、肿瘤直径及血行转移无关 ,与肺癌的组织学类型、淋巴结转移有关 ;VEGF表达阳性患者生存时间明显短于阴性患者 ,VEGF的表达与生存时间呈负相关。结论　不同性质的肺病变组织中 VEGF表达不同 ,可以作为 NSCL C临床诊断的可靠指标 ;VEGF和 NSCL C的转移、预后有关 ,可以作为判断预后的独立指标     

肺癌患者血清VEGF的表达及其临床意义

目的探讨血管内皮生长因子（VEGF）在肺癌患者血清中的表达及其临床意义。方法采用酶联免疫吸附法（ELISA）检测114例确诊的肺癌患者及87例对照者血清VEGF浓度,分别计算VEGF的灵敏度、特异度,分析其与临床特征的关系。结果肺癌患者血清VEGF平均浓度为203.70 ng/L,明显高于对照组的75.21 ng/L;以200.60 ng/L为医学参考值上限,其灵敏度为59.65%,特异度为95.40%;有瘤负荷组患者灵敏度可达到74.68%,而无负荷者仅为25.71%,其差别均有统计学意义（P〈0.001）。结论血清VEGF在肺癌中表达较高,可能在肿瘤的增殖、转移中发挥重要作用,是一个有价值的肺癌标记物。     

Serum levels of the angiogenic cytokines basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in multiple myeloma

Angiogenesis is a crucial process in growth and progression of cancer and there is growing evidence that neovascularisation is important in hematological malignancies. Since an increased angiogenic potential has been identified in multiple myeloma, we simultaneously measured circulating serum levels of the cytokines bFGF, VEGF, HGF and IL-6 by ELISA in 67 patients with multiple myeloma or monoclonal gammopathies of undetermined significance (MGUS) and in 20 controls. Median values of bFGF were 4.7 pg/ml in healthy volunteers, 6.2 in MGUS, 6.3 in myeloma stage I, 13.4 in stage II and 21.7 in stage III. Myeloma patients had significantly higher bFGF serum levels than controls (p<0.001). Pretreatment bFGF levels differed significantly in the Salmon and Durie stages I-III (p=0.02) and were significantly elevated in stage II-III compared to stage I myeloma (p=0.02). In patients responding to chemotherapy according to the CLMTF criteria, a significant decrease in serum bFGF, VEGF and HGF levels occurred (median pretreatment values for bFGF 23.9 pg/ml, post-treatment 6.5 pg/ml; p<0.001, for VEGF 223 pg/ml versus 105 pg/ml; p=0.02 and for HGF 1429 pg/ml versus 1077 pg/ml; p=0.02, respectively). In 11 patients who did not achieve a remission, there was no significant decrease in bFGF, VEGF and HGF levels. These data show that myeloma in stages II and III is associated with an increase in serum bFGF concentrations and give the first report that effective chemo-therapy is accompanied by a significant decrease in the angiogenic factors bFGF, VEGF and HGF, while no decrease of these factors could be found in nonresponders.     

膀胱移行细胞癌VEGF和VEGFR的表达及相关性的探讨

目的　探讨膀胱移行细胞癌 (BTCC)中血管内皮生长因子 (VEGF)及其受体 (VEGFR)的表达及与两者之间的关系。方法　采用免疫组织化学链霉菌抗生物素 过氧化物酶连接法 (S P法 )对 30例BTCC及 1 0例正常膀胱黏膜组织中VEGF及VEGFR的表达进行检测。结果　VEGF和VEGFR在绝大多数BTCC中呈阳性表达 ,平均表达率分别为 87%和 73 %。随肿瘤分期和分级的升高其表达水平升高 ,但在正常膀胱组织中未见表达。结论　BTCC中VEGF和VEGFR表达阳性 ,提示其在BTCC的血管生成和侵袭进展过程中起着重要作用 ,并将有可能为BTCC抗血管形成治疗及预防提供新的思路     

Role of vascular endothelial growth factor (VEGF) and placenta-derived growth factor (PlGF) in regulating human haemopoietic cell growth

Vascular endothelial growth factor (VEGF) and placental derived growth factor (PlGF) stimulate cell proliferation and differentiation by binding to their specific receptors, Flk-1/KDR and Flt-1 respectively. Flk-1/KDR-deficient murine embryos manifest failure of blood-island formation and vasculogenesis. The aim of this study was to directly evaluate the importance of VEGF, PlGF/Flt-1 and Flk-1/KDR receptor ligand interactions in regulating normal and malignant human haemopoiesis. Addition of VEGF and PlGF failed to enhance survival or cloning efficiency of human haemopoietic progenitors isolated from adult bone marrows, fetal livers or cord blood samples. This finding may be explained by the apparent absence of mRNA encoding Flt-1 and Flk-1/KDR receptors on stem cell rich CD34⁺ c-kit-R⁺ Rh123^low cells. Further studies revealed that Flt-1 R mRNA, but not Flk-1/KDR mRNA was first detectable in the more mature cells isolated from haemopoietic colonies. Accordingly, VEGF receptors are either absent, or expressed at very low level, on human haemopoietic stem/progenitor cells. Of interest, normal and malignant human haemopoietic cells appeared to secrete VEGF protein. However, in contrast to normal haemopoietic progenitors, VEGF co-stimulated HEL cell proliferation as well as CFU-GM colony formation from ∼15% of the chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) patients studied. Therefore, although VEGF appeared to have minimal effects on normal haemopoietic cell growth it would appear to drive malignant haemopoietic cell proliferation to some degree. Of more importance, however, we speculate that VEGF may play an very important role in leukaemogenesis by stimulating growth of vascular endothelium, thereby providing a sufficient blood supply to feed the growing haematological tumour.     

Vascular endothelial growth factor (VEGF) gene (VEGFA) polymorphism can predict the prognosis in acute myeloid leukaemia patients

Increased angiogenesis, mediated by vascular endothelial growth factor (VEGF), was associated with poor prognosis in acute myeloid leukaemia (AML) patients. The current study investigated the impact of VEGF gene ( VEGFA ) single nucleotide polymorphisms (SNPs) on treatment outcomes for AML. Four VEGFA SNPs were analysed for −2578C>A (rs699947), −460T>C (rs833061), +405G>C (rs2010963) and +936 C>T (rs3025039) loci in 138 AML patients. The +936 CC/CT genotype showed strong correlation with favourable leukaemia-free survival (LFS) at 2 years (51·3%) versus with +936 CC genotype (33·6%, P  =   0·03). Strong linkage disequilibrium was noted among loci −2578, −460 and +405, but not with +936. Accordingly, four haplotypes were generated based on the genotypes of −2578, −460 and +405 as follows: CTC (40·2%), CTG (35·0%), ACG (22·0%) and ATC (1·2%). The LFS and event-free survival (EFS) inversely correlated with CTG haplotype ( P  =   0·03 for LFS; P  =   0·05 for EFS). We scored the VEGFA polymorphism marker based on +936 C>T genotype and CTG haplotype for −2578, −460 and +405, which demonstrated a good correlation with the treatment outcomes: LFS ( P  =   0·01), EFS ( P  =   0·03) and overall survival ( P  =   0·01). The VEGFA +936 C>T genotype and CTG haplotype seemed to have an additive effect to predict the prognosis in AML patients.     

高糖环境下VEGF与PEDF在GMC中表达及rAAV-AS基因的干预作用

目的 探讨高糖对大鼠肾小球系膜细胞(GMC)色素上皮细胞衍生因子(PEDF) 和血管内皮生长因子(VEGF)表达影响以及腺相关病毒介导血管抑素(rAAV-AS)基因的干预作用.方法 将培养的大鼠GMC株分为6组,高糖作为刺激因素,rAAV-AS 作为干预因素.分别设低糖组、高糖组、高糖加腺相关病毒(rAAV)组及高糖加rAAV-AS 治疗组.用免疫细胞化学及ELISA法测定各组系膜细胞PEDF 以及VEGF蛋白表达.结果 高糖可下调GMC中PEDF蛋白的表达,上调GMC中VEGF蛋白的表达.rAAV-AS可逆转高糖导致GMC的VEGF蛋白表达的增加及PEDF蛋白表达的降低.结论 rAAV-AS可以一定程度改善高糖诱导的VEGF和PEDF表达失衡而发挥对糖尿病肾病(DN)的保护作用.     

Serum endostatin levels are elevated and correlate with serum vascular endothelial growth factor levels in patients with pituitary adenomas

Endostatin, a cleaved fragment of collagen XVIII, is a potent endogenous angiogenesis inhibitor. Elevated serum endostatin levels have been recently reported in patients with various types of neoplasms. The purpose of our study was to evaluate serum concentrations of endostatin in patients harbouring various pituitary adenoma types and to examine the relationship of serum endostatin levels to circulating vascular endothelial growth factor (VEGF) levels. Preoperative serum endostatin and VEGF concentrations were measured using competitive enzyme immunoassays in 71 patients with pituitary adenomas (20 somatotropinomas, 3 corticotropinomas, 6 prolactinomas and 42 clinically nonfunctioning pituitary adenomas – CNFPAs) and compared with levels from age-matched controls. In 35 patients postoperative immunohistochemical investigations were performed. Serum endostatin concentrations were significantly higher in all pituitary adenoma types, except for prolactinomas (somatotropinomas: 124 ± 16; p < 0.02, corticotropinomas: 157 ± 42; p < 0.02, prolactinomas: 141 ± 37; p > 0.05, CNFPAs: 169 ± 11 ng/ml; p < 0.000005 vs 73 ± 10 ng/ml in controls). There was a significant positive correlation between endostatin and VEGF serum levels in patients with pituitary adenomas (r = +0.322; p = 0.006). In the control group a significant negative correlation xbetween circulating endostatin and VEGF was found (r = −0.653; p = 0.00975). The simultaneous elevation of endostatin and VEGF may attenuate the pro-angiogenic action of VEGF and be responsible for rather weak neovascularization of pituitary adenomas. Prospective studies are required to assess the usefulness of circulating endostatin and VEGF as markers of progression or recurrence of pituitary tumors.