一种血管内皮生长因子变异体的结构与功能的初步探讨

目的针对发现的一种血管内皮生长因子变异基因(h′VEGF),利用计算机软件模拟预测其空间结构,并对其功能进行初步探讨。方法将pCD-hVEGF165及pCD-h′VEGF165重组真核表达载体导入CHO细胞,收集培养上清,进行ELISA分析、血管通透性实验(Miles实验)、内皮细胞增殖实验(MTT法)。结果h′VEGF165能使豚鼠的血管通透性增高,并促进ECV-304细胞增殖,但ELISA实验结果显示h′VEGF165与抗hVEGF165单抗未发生抗原抗体反应。结论h′VEGF165与hVEGF165在空间结构上可能存在差异,但现有的实验结果未见两者在功能上的明显差异。     

Immunohistochemical Expression of Vascular Endothelial Growth Factor in Canine Mammary Tumours

The histopathological and clinical aspects of canine mammary tumours (CMTs) have been widely studied, but the variation in the biological behaviour of these neoplasms hampers the identification of prognostic factors. Sustained angiogenesis has been suggested to be one of the most important factors underlying tumour growth and invasion. This process involves the action of several growth factors including vascular endothelial growth factor (VEGF). The present study characterizes the relationship between immunohistochemical expression of VEGF and gross (e.g. size and tissue fixation) and microscopical (e.g. type, growth, necrosis, lymphoid infiltration, lymph node metastasis, histological grade and proliferation index) features of CMTs. Forty-eight benign and 64 malignant CMTs were evaluated. Statistical analysis failed to show a significant relationship between VEGF expression and the pathological features, suggesting that VEGF expression occurs in both benign and malignant tumours and is independent of histological type, proliferation, tissue invasion or local metastatic capacity.     

2型糖尿病肾病患者血管内皮生长因子检测的临床意义

目的 :探讨了 2型糖尿病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例无糖尿病肾病和 5 5例糖尿病肾病患者血管内皮生长因子含量 ,并与 35名正常健康人作对照。结果 :2型糖尿病无肾病组和有肾病组血管内皮生长因子水平均高于正常人组 ,尤以糖尿病肾病为甚 (p <0 0 1 ) ,糖尿病肾病组与无糖尿病肾病组比较 ,差异也有显著性 (p <0 0 1 )。 结论 :2型糖尿病肾病的发生与发展与血管内皮生长因子水平密切相关。     

恶性肿瘤患者血清VEGF、IL-8水平与化疗疗效关系的研究

探讨血管内皮生长因子(VEGF)、白介素-8(IL-8)水平与恶性肿瘤临床分期、组织学分型等因素及化疗近期疗效之间的关系.采用定量ELISA方法分别检测53例恶性肿瘤患者化疗前血清VEGF与IL-8水平,其中25例经正规化疗后复查上述指标;10例对照为健康志愿者;同期还有CEA、CA125及CYFRA21-1或CEA及CA19-9两种肿瘤标志物组合检测.恶性肿瘤组化疗前血清VEGF及IL-8含量均明显高于对照组(P＜ 0.01),且随临床分期的进展而上升,但与肿瘤组织学类型及性别无明显相关性.化疗后血清VEGF及IL-8均显著下降(P＜ 0.01).VEGF、IL-8诊断肿瘤的阳性率高于瘤标组合并随临床分期进展而上升,联合检测可提高阳性率.VEGF和IL-8是肿瘤的发生、发展和转移的有效生物学指标.动态检测VEGF和IL-8化疗前后浓度变化能在一定程度上反映化疗近期疗效,可为临床选择治疗措施及判断预后提供有效帮助.     

Expression of Vascular Endothelial Growth Factor Isoforms in the Japanese Quail Embryo

Vascular endothelial growth factor (VEGF) is required for vascular development. In the quail, four VEGF isoforms formed by alternative splicing, are translated into proteins with 122, 146, 166, and 190 amino acids. VEGF isoforms differ biochemically, with variable affinities for heparan sulfate proteoglycans, the extracellular matrix and VEGF receptors. There are few data on the functional significance of VEGF isoforms. RT-PCR was used to examine isoform expression during quail vascular development. Our results suggest that all quail isoforms are expressed during establishment of the vascular pattern in whole embryos and extraembryonic tissues at apparently equal levels. No isoform-specific expression patterns were detected in isolated endoderm or between embryo halves.     

VEGF在翼状胬肉发病与复发中的作用

目的：探讨血管内皮生长因子（VEGF）在翼状胬肉发病与复发中的作用。方法：采用免疫组织化学方法检测42例初发与30例复发翼状胬肉标本中VEGF的表达情况,并与30例正常对照组比较。结果：VEGF表达阳性率：对照组为6.7%（2/30）,初发组为61.9%（26/42）,复发组为93.3%（28/30）,对照组低于初发组（P〈0.01）,初发组低于复发组（P〈0.05）。VEGF表达强阳性率：对照组为0%（0/30）,初发组为26.2%（11/42）,复发组为63.3%（19/30）,对照组低于初发组（P〈0.01）,初发组低于复发组（P〈0.01）。结论：VEGF的高水平表达是翼状胬肉发病与复发的重要原因。     

血管内皮生长因子与甲状腺疾病研究进展

血管内皮生长因子(VEGF)的基本功能是促进血管生长。近年研究表明,VEGF通过影响病灶处血管或癌细胞自身的生成从而在多种甲状腺疾病中发挥着重要作用。但VEGF的功能以及在不同甲状腺疾病中的具体变化情况仍然需要进一步探索。本文对VEGF的分子生物学及生物学特性、在多种甲状腺疾病中的作用及其临床应用进行简要综述。     

Isoflavone regulates Vascular Endothelial Growth Factor Expression in urinary tract of castrated rats

Objective

The purpose of this study was to investigate Vascular Endothelial Growth Factor Expression (VEGF) gene regulation by isoflavone in urinary tract tissues of castrated adult rats.

Design

Forty-five adult rats, 90 days old, weighting 200 g were used, receiving a soy-free ration. The animals were castrated for drug administration for 30 days (125 μg genisteine/g body weight/day) and sacrificed, divided into three groups: Group I—control; Group II—started isoflavone administration on the 5th day after castration; Group III—started isoflavone administration on the 28th day after castration. RNA was isolated from each bladder and urethra. Determination of VEGF gene regulated by isoflavone was obtained using a semiquantitative RT-PCR and immunohistochemistry of total RNA isolated from bladder and urethra.

Results

Our results demonstrate that isoflavone was able to upregulate mRNA level of the VEGF gene in the lower urinary tract of rats in Group II, where isoflavone administration was started at an early phase of estrogen deprivation, while in Group III, where isoflavone administration was started in the late phase of hypoestrogenism, did not show alteration of bladder and urethra VEGF gene expression, compared to placebo, maintaining the same level of the castrated rats without treatment.

Conclusions

The data indicate that VEGF expression in rats is also regulated by isoflavone in early phase of hypoestrogenism.     

Estradiol Down-Regulates LPS-Induced Cytokine Production and NFkB Activation in Murine Macrophages

PROBLEM: In vivo and in vitro studies have indicated that estradiol can affect cytokine production in different cell types. This study examines whether estradiol affects inflammatory cytokine production by murine splenic macrophages. METHODS: Mouse splenic macrophages were first treated with 17β-estradiol, followed by lipopolysaccharide (LPS) stimulation. The production of cytokines by macrophages with or without estradiol treatment was determined at both the protein and mRNA levels. The nuclear factor-kB (NFkB) activity of activated mouse splenic macrophages was also evaluated by electrophoretic mobility shift assay. RESULT: Our results show that 17β-estradiol decreases LPS-induced IL-1α, IL-6, and TNF-α production but not IL-10, IL-12, and macrophage inflammatory protein (MIP) production by splenic macrophages. Furthermore, inhibition of cytokine production by 17β-estradiol was associated with a decreased LPS-induced NFkB-binding activity. CONCLUSION: Because cytokines are important mediators of immune function, the alteration of cytokine production by 17β-estradiol may thus have a profound effect on the outcome of immune response during inflammation.     

Presence of HLA-G-Expressing Cells Modulates the Ability of Peripheral Blood Mononuclear Cells to Release Cytokines

PROBLEM: Human leukocyte antigen-G (HLA-G) is thought to be at play in maternal-fetal immune interplay during pregnancy. Whether the expression of HLA-G protein on the target cells altered the release of cytokines from effector mononuclear cells was questioned. METHOD OF STUDY: The amounts of cytokines released from peripheral blood mononuclear cells (PBMC) cocultured with or without HLA-G-expressing target cells were compared. RESULTS: When cocultured with HLA-G-expressing target cell lines, the amounts of interleukin-3 (IL-3) and interleukin-lβ (IL-1β) released from PBMC were increased, whereas the amounts of tumor necrosis factor-α (TNF-α) were decreased. CONCLUSIONS: Mononuclear cells, if cultured with HLA-G-expressing cells, modulate their ability to release cytokines, suggesting a role of HLA-G in triggering maternal-fetal immune interplay and thereby maintaining pregnancy.     

Vascular Endothelial Growth Factor D and Intratumoral Lymphatics as Independent Prognostic Factors in Epithelial Ovarian Carcinoma

Lymph node metastasis is an important prognostic indicator for disease progression and is crucial for therapeutic strategies of epithelial ovarian carcinoma. Vascular endothelial growth factor (VEGF)‐D has been confirmed to have potent lymphangiogenic function in experimental models, but the role in the progression of human ovarian carcinoma remains presently controversial. The purpose of this study was to investigate the prognostic significance of VEGF‐D and the presence of intratumoral lymphatics in patients with epithelial ovarian carcinoma. The VEGF‐D expression was evaluated by immunohistochemistry in 78 specimens of epithelial ovarian carcinoma and tumoral lymphatic vessels were measured by D2‐40. The expression of VEGF‐D protein was detected in the cytoplasm of the tumor cells and in stroma occasionally. The high expression of VEGF‐D was closely associated with the FIGO stage, intratumoral lymphatic vessels, tumoral lymphatic invasion, and lymph node metastasis as well as a shorter overall survival. Univariate and multivariate analysis indicated that VEGF‐D, intratumoral lymphatics, and lymphatic invasion were independent prognostic factors for overall survival and disease‐free survival in patients with epithelial ovarian carcinoma. We conclude that VEGF‐D plays an essential role in tumoral lymphangiogenesis and lymphatic spread, VEGF‐D expression, and the intratumoral lymphatics may be clinically useful indicators for prognostic evaluation in patients with epithelial ovarian carcinoma. Anat Rec, 2009. © 2009 Wiley‐Liss, Inc.     

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。     

The Angiogenic Peptide Vascular Endothelial Growth Factor–Basic Fibroblast Growth Factor Signaling is Up‐Regulated in a Rat Pressure Ulcer Model

The purpose of this study is to investigate the mRNA and protein expression levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in pressure ulcers, and to elucidate the molecular mechanism by which VEGF and bFGF are involved in pressure ulcer formation. A rat model of ischemia‐reperfusion pressure ulcer was established by magnetic disk circulating compression method. Real‐time fluorescence quantitative PCR and Western blot assays were conducted to detect the mRNA and protein expression of VEGF and bFGF in the tissues of rat I‐, II‐, and III‐degree pressure ulcers, the surrounding tissues, and normal skin. Our study confirmed that the mRNA and protein expression levels of VEGF and bFGF in the tissues of rat I‐degree pressure ulcer were significantly higher than that in the II‐ and III‐degree pressure ulcer tissues (P < 0.05). The expression of VEGF and bFGF in the tissues surrounding I‐ and II‐degree pressure ulcers were higher than the rats with normal skin. The expression of VEGF and bFGF in the tissues of rat III‐degree pressure ulcer was lower than that in the surrounding tissues and normal skin (P < 0.05). There was a significant positive correlation between change in the VEGF and bFGF. The results showed that with an increase in the degree of pressure ulcers, the expression of VEGF and bFGF in pressure ulcers tissue are decreased. This leads to a reduction in angiogenesis and may be a crucial factor in the formation of pressure ulcers. Anat Rec, 2013. © 2013 Wiley Periodicals, Inc.     

The Angiogenic and Lymphangiogenic Factor Vascular Endothelial Growth Factor-D Exhibits a Paracrine Mode of Action in Cancer

Vascular endothelial growth factor-D (VEGF-D) promotes angiogenesis, lymphangiogenesis and metastatic spread via the lymphatics, however, the mode of VEGF-D action (e.g. paracrine vs. autocrine) was unknown. We analyzed VEGF-D action in human tumors and a mouse model of metastasis. VEGF-D was localized in tumor cells and endothelium in human non-small cell lung carcinoma and breast ductal carcinoma in situ. Tumor vessels positive for VEGF-D were also positive for its receptors, VEGF receptor-2 (VEGFR-2) and/or VEGFR-3 but negative for VEGF-D mRNA, indicating that VEGF-D is secreted by tumor cells and subsequently associates with endothelium via receptor-mediated uptake. The mature form of VEGF-D was detected in tumors demonstrating that VEGF-D is proteolytically processed and bioactive. In a mouse model of metastasis, VEGF-D synthesized in tumor cells became localized on the endothelium and thereby promoted metastatic spread. These data indicate that VEGF-D promotes tumor angiogenesis, lymphangiogenesis and metastatic spread by a paracrine mechanism.     

血管内皮生长因子(VEGF)对培养内皮细胞VEGF受体表达的影响

目的 :为探讨VEGF对培养内皮细胞 (EC)VEGF受体表达的影响。方法 :将培养的人脐静脉内皮细胞 (HUVEC)随机分为 4组 :( 1)正常对照组 ;( 2 )低氧培养组 ;( 3)VEGF 10ng/ml组 ;( 4)低氧 +VEGF10ng/ml组。HUVEC低氧培养参照Kuwara等介绍的方法并加以改进。HUVECVEGF受体的检测采用免疫组织化学方法。结果 :采用简易低氧培养法 ,48h内培养液氧分压维持在 5 8mmHg ;与对照组相比 ,低氧培养组、VEGF组和低氧 +VEGF组HUVECVEGF受体Flk 1/KDR阳性细胞数增多 ,强度增加 ;但未检测到VEGF受体Flt 1表达。结论 :低氧可使HUVEC表面的VEGF受体Flk 1/KDR表达增加 ,VEGF同源上调其受体Flk 1/KDR ,低氧和VEGF在调节VEGF受体Flk 1/KDR方面有协调作用。     

Discovery and Functional Assessment of Gene Variants in the Vascular Endothelial Growth Factor Pathway

Angiogenesis is a host‐mediated mechanism in disease pathophysiology. The vascular endothelial growth factor (VEGF) pathway is a major determinant of angiogenesis, and a comprehensive annotation of the functional variation in this pathway is essential to understand the genetic basis of angiogenesis‐related diseases. We assessed the allelic heterogeneity of gene expression, population specificity of cis expression quantitative trait loci (eQTLs), and eQTL function in luciferase assays in CEU and Yoruba people of Ibadan, Nigeria (YRI) HapMap lymphoblastoid cell lines in 23 resequenced genes. Among 356 cis‐eQTLs, 155 and 174 were unique to CEU and YRI, respectively, and 27 were shared between CEU and YRI. Two cis‐eQTLs provided mechanistic evidence for two genome‐wide association study findings. Five eQTLs were tested for function in luciferase assays and the effect of two KRAS variants was concordant with the eQTL effect. Two eQTLs found in each of PRKCE, PIK3C2A, and MAP2K6 could predict 44%, 37%, and 45% of the variance in gene expression, respectively. This is the first analysis focusing on the pattern of functional genetic variation of the VEGF pathway genes in CEU and YRI populations and providing mechanistic evidence for genetic association studies of diseases for which angiogenesis plays a pathophysiologic role.     

急性白血病患者治疗前后血浆VEGF水平的临床意义

目的：探讨急性白血病患者血管内皮生长因子水平的变化。方法：应用酶联双抗体夹心法测定了34例急性白血病患者血管内皮生长因子的含量，并与35名正常健康人作比较。结果：急性白血病患者在治疗前血管内皮生长因子含量非常显著地高于正常人组（P〈0．01），经抗癌和中西医结合治疗三个月后与正常人组比较，仍有显著性差异（P〈0．05）。结论：急性白血病的发生与发展与血管内皮生长因子水平密切相关。     

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。     

血管内皮细胞生长因子VEGF与细胞黏附分子CD15在骨肉瘤中的表达及意义的研究现状

目的 探讨血管内皮细胞生长因子VEGF与细胞黏附分子CD15在骨肉瘤中的表达及意义的研究现状.方法 通过查阅大量文献,对VEGF与CD15的相关性以及两者对骨肉瘤的作用和临床治疗的研究进展做综合分析、评价.结果 VEGF与骨肉瘤的发生密切相关,但与骨肉瘤的转移尚有争论,而CD15与肿瘤的转移有密切关系.特别是已经发生转移的骨肉瘤患者中是否存在VEGF和CD15的高表达,尚待进一步证实.有可能通过针对VEGF与CD15的研究,研发出新的临床药物,以提高高度恶性的骨肉瘤患者的生存率,并对患者的预后作出有效的评估.结论 通过对VEGF和CD15进行实验研究,很有可能找到治疗骨肉瘤的新的基因治疗靶点.