神经电生理检查在肌萎缩侧索硬化症中的应用

目的:观察神经电生理检查在肌萎缩侧索硬化症(amyotrophic lateral sclerosis,ALS)中的应用价值。方法:分别对28例临床确诊ALS、6例临床拟诊ALS、4例临床可能ALS患者进行4个区域的共8块肌肉肌电图(EMG)分析,四肢的磁运动诱发电位(MEP),上肢正中神经、尺神经、下肢胫神经F波检查,在双侧腓肠肌记录H波,四肢远端神经传导测定,包括运动传导速度(MCV)、感觉传导速度(SCV)、复合运动神经动作电位(CMAP)、感觉神经动作电位(SNAP)以及运动末梢潜伏期(DML)进行测定并分析,并与健康对照组30例进行比较。结果:临床确诊ALS的神经电生理测定各值异常均高于拟诊ALS和可能ALS(P<0.05),拟诊ALS和可能ALS组比较没有明显统计学差异。ALS组EMG异常率85%,MEP异常率72.4%,神经传导异常主要表现为CMAP降低36.2%,SCV基本正常,F波出波率下降33.3%,F波振幅增高26.3%,H波振幅增高26.3%。结论:EMG对ALS患者下运动神经元损害有定位诊断价值,EMG是ALS诊断的重要依据;MEP对ALS患者上运动神经元损害有诊断价值,但特异性不高;F波、H波对ALS患者上下神经元神经损害定位有补充诊断价值,神经传导测定用于ALS的鉴别诊断。     

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。     

Validation of anti-vascular endothelial growth factor (anti-VEGF) antibodies for immunohistochemical localization of VEGF in tissue sections: expression of VEGF in the human endometrium

Transient transfection of COS-1 cells followed by fixation, embedding in paraffin, and immunohistochemistry has identified anti-vascular endothelial growth factor (anti-VEGF) mouse monoclonal antibodies that efficiently immunostain VEGF in paraffin-embedded tissue sections. Immunohistochemical localization of VEGF in 34 specimens of normal human endometrium that had been collected at different stages of the menstrual cycle was then performed. VEGF was present at all stages of the cycle, but both the pattern and the intensity of staining varied. Thus, VEGF expression occurred predominantly in the endometrial epithelium and while weak in the proliferative phase, was strong in the secretory phase. VEGF expression in the stroma was weaker than in the proliferative phase glands and did not change throughout the cycle. These findings are in agreement with reports of VEGF mRNA expression in the endometrium, but disagree with previous immunohistochemical studies that employed an immunohistochemically unvalidated antiserum. This study has shown that the commercially available anti-VEGF monoclonal antibody M293 is excellent for the immunohistochemical localization of VEGF in paraffin sections. © 1998 John Wiley & Sons, Ltd.     

Peripheral blood mononuclear cells from patients with systemic sclerosis spontaneously secrete increased amounts of vascular endothelial growth factor (VEGF) already in the early stage of the disease

PurposeTo investigate the capacity of the peripheral blood mononuclear cells (PBMC) from patients with systemic sclerosis (SSc) to produce vascular endothelial growth factor (VEGF), and to identify clinical associations of altered production of VEGF by PBMC in SSc. In addition, correlation with another pro-angiogenic cytokine, TNF-related weak inducer of apoptosis (TWEAK), was evaluated.MethodsPBMC were isolated from 25 patients with SSc and 17 healthy controls (HC). VEGF and TWEAK were measured in the supernatants of cultured PBMC using commercially available ELISA kits.ResultsPBMC from SSc patients spontaneously released significantly greater amounts of VEGF as compared with HC. Production of VEGF was comparable between patients with early SSc and those with longer disease duration, and in both SSc groups higher than in HC. Patients without active digital ulcers produced significantly greater amounts of VEGF as compared with HC, while there was no significant difference in the production of VEGF between SSc patients with active digital ulcers and HC. VEGF/TWEAK ratio was significantly higher in PBMC from SSc patients than in HC indicating that high production of VEGF is not paralleled by increased release of TWEAK in SSc.ConclusionsPBMC form SSc patients produce increased amounts of VEGF already in the early stage of disease. There is an imbalance in the profile of pro-angiogenic mediators produced by PBMC in SSc which might contribute to the pathogenesis of SSc. Further studies should address clinical significance of our findings.     

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.     

Neuropathology of Olfactory Ensheathing Cell Transplantation into the Brain of Two Amyotrophic Lateral Sclerosis (ALS) Patients

Although a large number of amyotrophic lateral sclerosis (ALS) patients have undergone transplantation procedures with olfactory ensheathing cells (OECs) in the Bejing Hospital, to our knowledge, no post‐mortem neuropathologic analyses have been performed. We examined the post‐mortem brain of two Italian patients affected by ALS who underwent cellular transplantation in Beijing with their consent. Our aim was to assess the events following the graft procedure to possibly support the rationale of the treatment strategy. The neuropathologic findings were analyzed on the basis of the limited awareness of the experimental conditions and discussed in relation to the safety, efficacy and long‐term outcome of the transplanted cells. Islands of quiescent, undifferentiated cells within the delivery track persisting for up to 12 months–24 months were found. Prominent glial and inflammatory reaction around the delivery track strongly supports the encasement of the graft. Evidence of axonal regeneration, neuronal differentiation and myelination was not seen. The surgical procedure of implantation was not compatible with a neurotrophic effect. The OEC transplantation did not modify the neuropathology of ALS in the two patients. In conclusion, the present neuropathologic analysis does not support a beneficial effect of fetal OEC implantation into the frontal lobes of ALS patients.     

血管内皮生长因子的神经保护作用

血管内皮生长因子(vascularendothelial growth factor,VEGF)是内皮细胞特异性的生长因子,大多数关于VEGF的研究都是致力于其在血管生长方面的作用,而近年来有大量文献报道VEGF具有神经营养和促神经发生作用,它能够直接作用于神经元细胞和神经胶质细胞甚至是神经干细胞,促进其生长及存活。VEGF的多种功能使其和多种神经退行性疾病相关,如阿茨海默病,肌萎缩侧索硬化症,帕金森病等。导入VEGF基因能够改善肌萎缩侧索硬化症、帕金森病动物模型的病情。     

乳腺癌患者血清Leptin和VEGF的表达

目的：研究瘦素（Leptin）、血管内皮生长因子（VEGF）在乳腺癌患者血清中的表达，探讨其在乳腺癌诊断中的意义。方法：选择乳腺癌患者36例，乳腺良性增生病变患者31例，另选56例健康女性作为对照。分别用放射免疫分析（RIA）和酶联免疫吸附试验（ELISA）测定这些患者术前血清Leptin、VEGF。结果：正常对照组与良性病变组、乳腺癌组Leptin存在明显差异，正常对照组与乳腺癌组，良性病变组与乳腺癌组VEGF存在明显差异。乳腺癌患者术前血清Leptin、VEGF含量与有无淋巴结转移具有相关性。结论：乳腺癌患者术前血清Leptin、VEGF可作为鉴别乳腺良恶性肿瘤有无转移的指标。     

血管内皮生长因子及其可溶性血管内皮生长因子受体-1水平与胎儿出生体重

目的本研究通过对比血管内皮生长因子(VEGF)、可溶性血管内皮生长因子受体-1(sFlt-1)水平差异与新生儿出生体重的关系,以探讨其在胎儿出生体重发生中的作用。方法采用免疫组织化学法检测40例分娩正常出生体重儿组(AGA组)、30例高出生体重儿组(LGA组)及30例低出生体重儿组(SGA组)胎盘组织中VEGF、sFlt-1的表达水平。结果①LGA组胎盘组织中VEGF的表达高于AGA组,sFlt-1的表达水平低于AGA组,差异有统计学意义(χ2=21.17,P<0.01)。SGA组胎盘组织中VEGF的表达低于AGA组,sFlt-1的表达水平高于AGA组,差异有统计学意义(χ2=8.44,P=0.04)。②胎盘组织中VEGF的表达水平与胎儿出生体重呈正相关(r=0.427,P<0.01),胎盘组织中sFlt-1的表达水平与胎儿出生体重呈负相关(r=-0.569,P<0.01)。结论孕妇胎盘组织中VEGF及sFlt-1表达水平的变化可能与胎儿出生体重有关。     

Differences of vascular endothelial growth factor (VEGF) expression between liver and abdominal metastases from colon cancer. Implications for the treatment with VEGF inhibitors

The vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis, and it is the target of innovative anti-cancer therapies. In colorectal carcinomas, differences in the VEGF expression have been found between the primary tumor and its metastases. We postulated that differences in the VEGF expression may also exist between liver and abdominal metastases from colon cancer. Consecutive colon cancer patients with liver or abdominal metastases were considered eligible for the study. Biopsies had to be performed before chemotherapy and the VEGF analysis were conducted through immunohistochemistry. The staining results were correlated to the metastatic pattern. The study population consisted of 41 patients with a metastatic site in the liver in 19 patients and the abdomen in 22 patients. A positive VEGF staining was found in 19 of the 41 metastatic samples (46%). Cases with positive VEGF expression were found more frequently in abdominal (15 out of 22 patients; 68%) than in liver metastases (4 out of 19 patients; 21%). Also, the degree of VEGF immunoreactivity was significantly higher in abdominal than in liver metastases. Evidence is supported that the VEGF expression may be different between colon cancer metastatic sites. The efficacy of anti-VEGF treatments may depend on the VEGF expression status, and this finding deserves further investigation. This revised version was published online in July 2006 with corrections to the Cover Date.     

血管内皮生长因子及其受体在肝癌细胞中的表达及意义

目的 探讨人肝癌细胞株血管内皮生长因子（VEGF）及其受体的表达,进一步认识VEGF在肝癌血管形成中的作用机制,方法 以人脐静脉血管内皮细胞系ECV304和小鼠成纤维细胞系L929作为对照,采用免疫组化染色及RT-PCR,检测体外培养的人肝细胞肝癌细胞系SMMC7721、HHCC和HepG2中VEGF及其受体的表达。结果 SMMC7721、HHCC和HepG2细胞均有VEGF的表达。同时VEGF受体1（Flt-1)在SMMC7721细胞中也有表达;而HHCC和HepG2细胞则表达VEGF的受体2（KDR）。结论 在肝癌的血管形成中可能存在VEGF的自分泌机制。     

VEGF与血液学恶性疾病

VEGF作为一种血管新生的主要病理生理性调节因子，触发了白血病细胞及多发性骨髓瘤细胞的生长、存活及移动，在造血过程中起重要作用。VEGF的表达及其信号转导，对血液学恶性疾病，尤其是对多发性骨髓瘤的发病机制及临床特性都有重要作用。针对VEGF及其受体直接或间接的治疗，有可能为临床提供一种新的有效的治疗方法。     

Expression of vascular endothelial growth factor (VEGF) and its two receptors (VEGF-R1-Flt1 and VEGF-R2-Flk1/KDR) in non-small cell lung carcinomas (NSCLCs): correlation with angiogenesis and survival

The formation of new vessels (angiogenesis) is essential for primary tumour growth and metastasis and is induced by several angiogenic factors, including vascular endothelial growth factor (VEGF). The microvascular density (MVD) in tumours was assessed and the expression of VEGF and its receptors VEGF-R1-Flt1 and VEGF-R2-KDR/Flk1 was investigated in the different cellular compartments in vivo, in order to establish their interrelationship and their prognostic influence. Immunohistochemical study of 69 stage I–II non-small cell lung carcinomas (NSCLCs) was performed on paraffin sections with CD34 antibody to estimate MVD, using a Chalkley eye-piece graticule and VEGF, VEGF-R1, and VEGF-R2 antibodies. There was strong expression of VEGF and its receptors in tumour cells, endothelial cells, and stromal fibroblasts. In tumour cells, the level of VEGF was correlated with that of VEGF-R1 ( p = 0·018) but not that of VEGF-R2. In fibroblasts, high expression of VEGF was correlated with that of VEGF-R1 ( p = 0·0001) and VEGF-R2 ( p = 0·0001). In endothelial cells, expression of VEGF was correlated with that of VEGF-R1 ( p < 0·0001) and VEGF-R2 ( p = 0·04). The level of VEGF in fibroblasts was correlated with that of VEGF-R1 ( p = 0·0028) and VEGF-R2 ( p = 0·01) in endothelial cells. There was no correlation between the level of MVD and that of VEGF or VEGF-R1 or VEGF-R2. Neither the level of MVD, nor the level of expression of VEGF and VEGF receptors in any compartment influenced the patient's survival. In conclusion, although angiogenesis is essential for tumour growth, this study failed to demonstrate that MVD, VEGF, VEGF-R1, and VEGF-R2 are prognostic markers for stage I–II NSCLC. VEGF, however, might act as a direct autocrine growth factor for tumour cells via VEGF-R1 and angiogenesis could be promoted in a paracrine loop, where VEGF is produced by fibroblasts and tumour cells and then binds to endothelial cells via induced VEGF receptors. VEGF and its receptors thus appear as relevant therapeutic targets in NSCLC. Copyright © 1999 John Wiley & Sons, Ltd.     

Expression of VEGF and VEGF-R3 receptor by placental endothelial cells in health and gestosis

We carried out a comparative analysis of changes in VEGF secretion and expression of VEGF-R3 receptor by placental endothelial cells in health and gestosis and of changes in VEGF-R3 expression by EA.hy926 human endothelial cells during culturing with supernatants conditioned by placental explants from women with normal pregnancy and patients with gestosis. Reduced secretion of VEGF and expression of VEGF-R3 by placental endothelial cells in gestosis can be caused by functional deficiency of the endothelial cells and low viability of endothelial cells. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 3, pp. 321–325, March, 2008     

血管内皮细胞生长因子及其受体2在慢性砷染毒大鼠睾丸中的表达及其意义*

目的：研究血管内皮细胞生长因子（ VEGF）及其受体2（ VEGFR2）在慢性砷中毒大鼠睾丸中的表达及意义。 方法：健康清洁级雄性SD大鼠随机分为高、中、低剂量砷染毒组和对照（ 蒸馏水）组,采用经口自由饮用方式 进行染毒,连续染毒6 个月。H-E 染色观察睾丸一般形态学变化,免疫荧光化学法对睾丸组织VEGF 和VEGFR2 的表达进行定位,采用实时荧光定量PCR法检测睾丸组织VEGF 和VEGFR2 的mRNA表达变化,流式细胞术观 察精子的凋亡率。结果：与对照组比较,中、高剂量砷组大鼠体质量明显降低,睾丸组织质量也明显降低,而低 剂量砷组大鼠体质量、睾丸质量、睾丸脏器系数差异无统计学意义。对照组睾丸结构正常,染砷组大鼠睾丸组织 上皮结构疏松,层次排列紊乱,层次逐渐减少,精原细胞出现空泡样改变,睾丸间质充血、渗出等,尤其中、高 剂量砷组有较明显的变化。与对照组比较,各染毒组VEGF 和VEGFR2 的mRNA表达水平均较低,砷染毒组大鼠 精子凋亡率较高,差异均有统计学意义。结论：慢性砷中毒时,VEGF 可能通过旁分泌- 自分泌的方式参与调控 大鼠睾丸的功能,VEGF 及其受体2 在砷中毒大鼠精子发生和发育过程中起重要作用。     

小儿肾病患者治疗前后VEGF检测的临床意义

目的 :探讨了小儿肾病患者血管内皮生长因子的水平。方法 :应用酶联双抗体夹心法测定了 31例小儿肾病患者血管内皮生长因子的含量 ,并以 35名正常健康人作比较。结果 :小儿肾病患者血浆中血管内皮生长因子水平非常显著地高于正常人组 (P <0 0 1) ,经治疗一个月后与正常人比较仍有差异 (P <0 0 5 )。结论 :小儿肾病的发生、发展与血管内皮生长因子水平密切相关。     

Gender-specific association between polymorphism of vascular endothelial growth factor (VEGF 936C>T) gene and patients with stomach cancer

Purpose

Angiogenesis plays an important role in the growth, progression, and metastasis of tumors. Vascular endothelial growth factor (VEGF) overexpression has been associated with advanced stage and poor survival in several cancers. We investigated the present case-control study to determine whether there is an association between the VEGF 936C > T polymorphism and stomach cancer.

Patients and Methods

The association of functional single nucleotide polymorphisms (SNPs) of the VEGF gene with stomach cancer development was evaluated in a case-control study of 154 Korean stomach cancer patients. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.

Results

Our results revealed significant association of T allele-bearing genotypes with increased risk for stomach cancer development. Genotype frequencies of the VEGF 936C > T polymorphisms were significantly different between patient and control groups (CT, AOR: 2.007, 95% CI: 1.277 - 3.156, TT, AOR: 4.790, 95% CI: 1.174 - 19.539, CT + TT, AOR: 2.147, 95% CI: 1.382 - 3.337). When stratified by gender and age, genotype frequencies were significantly different for stomach cancer in women and in patients younger than 55 years (in women, CT, OR: 3.049, 95% CI: 1.568 - 5.930, CT+TT, OR: 3.132, 95% CI: 1.638 - 5.990; in < 55 years, CT, OR: 3.306, 95% CI: 1.413 - 7.732, CT + TT, OR: 3.967, 95% CI: 1.729 - 9.104). In addition, this association partially remained in cases with intestinal and diffuse-type stomach cancer.

Conclusion

Our present study suggests that the VEGF 936C > T polymorphism is a susceptibility factor for stomach cancer, at least in Korean.     

小儿隐睾症手术治疗前后VEGF检测的临床意义

目的:探讨了小儿隐睾症患者血管内皮生长因子水平。方法:应用酶联双抗体夹心法测定了30例小儿隐睾症患者血管内皮生长因子的含量,并以35名正常健康儿童作比较。结果:小儿隐睾症患者血浆中血管内皮生长因子水平非常显著地高于正常人组(P<0.01),经手术治疗3个月后与正常人比较无显著性差异(P>0.05)。结论:小儿隐睾症的发生、发展与血管内皮生长因子水平密切相关。     

Angiogenesis in craniopharyngiomas: Microvascular density and tissue expression of the vascular endothelial growth factor (VEGF) and endostatin

Craniopharyngiomas are benign tumors of the sellar region generally associated with endocrine abnormality and often locally aggressive. Several studies have demonstrated that angiogenesis or neovascularization plays an important role in tumoral growth. The microvascular density (MVD) of craniopharyngiomas was determined in tumor tissue samples from a reference neurosurgery center located in southern Brazil using immunohistochemical methods for two endothelial markers, CD34 and CD105 (endoglin). In addition, tissue expression was determined for an angiogenesis stimulatory factor and for one of its inhibitors, the vascular endothelial growth factor (VEGF) and endostatin, respectively. Endothelial cell immunoreactivity for CD34 and CD105 was observed scattered within the stroma. MVD determined using CD105 antigen was significantly lower than the results obtained by using CD34 antigen. There was no association between the two endothelial markers and tumor extension. The epithelial component showed different degrees of immunoreactivity for VEGF and endostatin in all samples analyzed. We were not able to establish a relationship between angiogenesis in craniopharyngiomas and tumor extension with the endothelial markers used in this study. The investigated vascularization stimulatory and inhibitory factors showed no relation with MVD. We believe that CD105 antigen can be a more specific endothelial marker for tumor angiogenesis than CD34 antigen.