VEGF家族新成员:VEGF-B,VEGF-C和VEGF

血管内皮生长因子（ Ｖ Ｅ Ｇ Ｆ） 近年又发现了下列新成员： Ｖ Ｅ Ｇ Ｆ Ｂ, Ｖ Ｅ Ｇ Ｆ Ｃ 及 Ｖ Ｅ Ｇ Ｆ Ｄ,三种因子与 Ｖ Ｅ Ｇ Ｆ 具有相似的结构、功能及分布。 Ｖ Ｅ Ｇ Ｆ Ｂ 的受体尚未明确,该因子具有促进内皮细胞生长的功能; Ｖ Ｅ Ｇ Ｆ Ｃ 主要作用于淋巴管内皮,其受体为 Ｖ Ｅ Ｇ Ｆ Ｒ２ 和 Ｖ Ｅ Ｇ Ｆ Ｒ３ ; Ｖ Ｅ Ｇ Ｆ Ｄ 与 Ｖ Ｅ Ｇ Ｆ Ｃ 的作用及结构相似,受体相同。     

人乳腺癌组织中VEGF-C和iNOS的表达及意义

目的研究人乳腺癌组织中血管内皮生长因子-C(vascular endothelial growth factor-C,VEGF-C)和诱生型一氧化氮合酶(inducible nitiric oxide synthase,iNOS)的表达并探讨两者的相关性。方法采用免疫组织化学SABC法检测50例乳腺癌组织和癌旁正常乳腺组织中VEGF-C和iNOS的表达,并分析其相互关系。结果 VEGF-C和iNOS在乳腺癌组织中均呈强阳性表达,而在癌旁正常组织则不表达。VEGF-C的表达与患者年龄、肿瘤大小、分化程度及临床分期无关(P>0.05),而与淋巴结转移密切相关(P<0.05)。iNOS的表达与患者年龄及肿瘤大小无关(P>0.05),而与分化程度、临床分期及淋巴结转移密切相关(P<0.05)。VEGF-C和iNOS的表达呈正相关(γ=0.43,P<0.05)。结论 VEGF-C和iNOS蛋白在乳腺癌的发生中具有协同作用,两者可能共同参与肿瘤淋巴管的生成。     

多发性浅表膀胱移行细胞癌中VEGF的表达及意义

目的:探讨单发性和多发性浅表膀胱移行细胞癌组织中血管内皮生长因子(VEGF)的表达及意义。方法:采用免疫组化方法对60例浅表膀胱移行细胞癌组织及10例正常膀胱组织进行血管内皮生长因子(VEGF)的检测,观察单发性和多发性浅表膀胱移行细胞癌组织中VEGF表达的关系。结果:多发性浅表膀胱移行细胞癌VEGF的高表达明显高于单发者的高表达;VEGF高表达的浅表膀胱移行细胞癌的患者的复发率明显高于低表达者的复发率。结论:VEGF表达的高低与浅表膀胱移行细胞癌的生物学行为有关。     

喉癌组织中VEGF—C和VEGF-D的研究新进展

目的：探讨喉癌中VEGF—C与VEGF—D的表达及其与淋巴转移的关系。方法：搜集整理新近发表的相关文献,进行归纳总结。结果：VEGF—C及VEGF—D在各种肿瘤组织中的表达均显著增高。喉癌中二者的表达高于癌周及正常组织,且有淋巴转移组的表达高于无淋巴转移组。结论：喉癌的淋巴转移和VEGF-C及VEGF-D的表达相关,阻断VEGF—C／VEGF-D／VEGFR-3通路的表达有望成为抗肿瘤淋巴转移的新手段。     

乳腺癌组织中VEGF的表达及临床意义

目的：探讨乳腺癌组织中血管内皮生长因子（VEGF）的表达及其临床病理意义。方法：采用快捷免疫组化MaxVisionTM法，对68例乳腺癌组织和22例乳腺良性病变组织中VEGF的表达进行检测，结合临床及病理形态学资料进行统计分析。结果：VEGF的阳性表达率为乳腺癌42．6，乳腺良性病变组织中为5．02，两者比较，差异均有统计学意义（均P〈0．05）。VEGF的表达与乳腺癌患者年龄、肿瘤大小及组织学分型无关，而与乳腺癌组织学分级、临床分期和腋窝淋巴结转移有关（P〈0．05）。结论：VEGF可能与乳腺癌的进展、转移及预后有关，作为独立的指标对判定预后和制定治疗方案具有参考意义。     

贲门腺癌中VEGF-C、VEGF-D和D2-40的表达及意义

目的 以一种新的淋巴管特异标记物D2-40标记贲门腺癌(gastric cardiac adenocarcinoma, GCA)及癌周组织淋巴管,并进行淋巴管计数,研究其与VEGF-C 、VEGF-D表达的关系及其临床病理意义.方法应用免疫组化SP法检测贲门癌、癌旁及正常黏膜组织中VEGF-C、VEGF-D、D2-40的表达情况.结果 癌及癌旁组中淋巴管密度(lymphatic vessel density,LVD)明显高于正常组(P<0.05),而癌组与癌旁组间LVD统计学无明显差异.癌组织中LVD与淋巴结转移、TNM分期及肿瘤浸润深度呈正相关(P<0.01),而与分化程度无关;VEGF-C、VEGF-D在贲门癌中的表达明显高于癌旁组和正常组(P<0.01);癌组织中LVD在VEGF-C和VEGF-D表达阳性组中高于阴性组(P<0.05);LVD与VEGF-C、VEGF-D的表达呈正相关(P<0.05).结论 贲门癌及癌周间质中D2-40标记的LVD升高可能增加了贲门癌淋巴结转移的风险;D2-40、 VEGF-C、VEGF-D的联合检测可作为评估贲门癌淋巴结转移潜能的标志物,并且对其预后评估有一定的价值.     

VEGF-B和VEGF-C的研究进展

ＶＥＧＦＢ 和ＶＥＧＦＣ 是近来发现的血管内皮生长因子（ＶＥＧＦ） 家族的两个新成员,ＶＥＧＦＢ有两种存在形式,即ＶＥＧＦＢ１６７ 和ＶＥＧＦＢ１６８ ,主要表达于胚胎及成人的肌肉组织（ 心肌及平滑肌） ,可通过与ＶＥＧＦＲ１／ＦＬＴ１ 结合发挥促血管生成的作用。ＶＥＧＦＣ 主要表达于胚胎中富含淋巴管的区域及成人的心脏、胎盘、卵巢、小肠和甲状腺等,能通过与ＶＥＧＦＲ２ 及ＶＥＧＦＲ３／ＦＬＴ４ 结合,发挥促血管、淋巴管形成及维持淋巴内皮细胞功能的作用。二者的发现使ＶＥＧＦ家族的成员进一步扩大并说明了内皮细胞功能调节的复杂性。     

血浆VEGF水平在维吾尔族妇女子宫内膜癌中表达及意义

目的探索血浆血管内皮生长因子（VEGF）在子宫内膜癌中的表达。方法收集新疆地区50例维吾尔族子宫内膜样腺癌患者血浆,收集40例健康维吾尔族妇女血浆为正常对照。用酶联免疫法测血浆VEGF含量,分析子宫内膜癌同血管内皮生长因子的相关性。分析子宫内膜癌各临床分期及分化程度血浆VEGF的变化状况。结果子宫内膜样腺癌血浆VEGF水平同正常对照血浆相比差异有统计学意义（P〈0．01）;晚期（Ⅲ期、Ⅳ期）子宫内膜样腺癌血浆VEGF增高的水平与早期（Ⅰ期、Ⅱ期）子宫内膜样腺癌相比差异有统计学意义（P〈0．01）,在不同分化程度的子宫内膜样腺癌中,随着分化程度的加重,血浆VEGF水平增高,各组相比差异有统计学意义（P〈0．05）。结论子宫内膜癌与血浆VEGF水平增高相关,血浆VEGF水平与临床分期、分化程度相关,临床分期晚的和分化程度低的血浆VEGF水平增高更加明显。     

VEGF和C-myc表达在胆囊癌形成、发展和转移中的作用

应用免疫组化ABC法对30例胆囊癌的癌组织VEGF和C－myc的表达进行检测，以探讨VEGF和C－myc在胆囊癌中的表达和二者之间的相关性以及胆囊癌形成，发展和转移中的作用。结果发现VEGF和C－myc二者在胆囊癌组织和正常胆囊组织中的阳性表达率均有显著性差异（P＜0．05），VEGF与C－myc的表达呈非常显著的相关性（P＜0．01），二者的表达与胆囊癌的转移行为有关，而与肿瘤的分化程度无关，VEGF与C－myc基因协同作用在胆囊癌形成，发展和转移中起着重要作用。     

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。     

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.     

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。     

血管内皮生长因子C及其受体3在非小细胞肺癌组织中的表达及意义

目的　探讨血管内皮生长因子C(VEGF C)和受体 (VEGFR) 3在人非小细胞肺癌(NSCLC)组织中的表达及其与微血管、微淋巴管形成、淋巴转移、预后之间的关系。方法　对 76例人NSCLC及相应癌旁组织行VEGF C、VEGFR 3及CD34免疫组织化学染色链霉素抗生物素蛋白 过氧化物酶 (SP)法检测 ,进行淋巴管密度计数、微血管密度 (MVD)计数 ,并结合临床和病理资料进行分析。结果　NSCLC中 ,VEGF C的表达与肺癌分化程度负相关 (P =0 0 0 9)。VEGF C和VEGFR 3的表达水平与淋巴结转移呈正相关 (分别P =0 0 0 8,P =0 0 13) ,与淋巴浸润呈正相关 (分别P =0 0 2 7,P =0 0 2 0 )。VEGF C的表达与VEGFR 3在肺癌细胞中的表达呈正相关 (P =0 0 0 9)。VEGF C与淋巴管密度 (P =0 0 0 6 )、MVD(P =0 0 4 6 )呈正相关。淋巴管密度与淋巴结转移 (P =0 0 10 )、淋巴浸润 (P =0 0 19)、TNM分期 (P =0 0 15 )呈正相关 ,MVD与血行转移 (P <0 0 0 1)、TNM分期 (P <0 0 0 1)呈正相关。VEGF C阳性表达与生存时间、5年生存率呈负相关 (P <0 0 0 1)。结论　NSCLC中 ,VEGF C通过自分泌方式作用于受体VEGFR 3,促进肺癌组织生长 ,抑制分化。VEGF C促使肺癌内淋巴管形成 ,促进肺癌淋巴结转移。VEGF C和VEGFR 3表达增高、淋巴管密度增加     

血管内皮细胞生长因子在肥胖乳腺癌患者乳腺癌组织中的表达及临床意义

 摘要：　目的 探讨肥胖乳腺癌患者乳腺癌组织中血管内皮细胞生长因子（vascular endothelial growth factor,VEGF）的表达及临床意义。方法 采集45例肥胖乳腺癌患者,37例正常体重乳腺癌患者,用RT-PCR和免疫组织化学检测肥胖组和正常体重组乳腺癌组织VEGF的mRNA和蛋白表达。结果 肥胖组乳腺癌组织VEGF的mRNA和蛋白表达均高于正常体重组 (P<0.05),并且VEGF mRNA和蛋白表达之间呈正相关(r=0.785,P<0.05);VEGF在肥胖乳腺癌组织中的表达与组织学分级、5年复发转移有关,与患者年龄无关。结论 VEGF在肥胖乳腺癌患者中具有高表达趋势,提示VEGF可能在肥胖相关性乳腺癌的发生、演变及预后中起重要作用。     

Expression of vascular endothelial growth factor in human gastric carcinomas

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a secreted protein which may play a pivotal role in tumor-associated microvascular angiogenesis and hyperpermeability. The expression of mRNA for VEGF was examined in eight gastric carcinoma cell lines and 30 gastric carcinoma tissues as well as corresponding normal mucosa. All the cell lines expressed VEGF mRNA at various levels that correlated well with the amounts of VEGF secreted into the condition medium. The expression of VEGF mRNA by TMK-1 cells was increased by the treatment of epidermal growth factor (EGF) or interleukin-1α (IL-1α), whereas it was decreased by the treatment of interferon-β (IFN-β). In gastric carcinoma tissues, the level of VEGF mRNA in primary tumors was higher than that in the corresponding normal mucosas in six (46%) of 13 well-differentiated adenocarcinomas and in two (12%) of 17 poorly differentiated adenocarcinomas, respectively. Vessel counts in well-differentiated adenocarcinomas had a tendency to be higher than those in poorly differentiated adenocarcinomas. In well-differentiated adenocarcinomas, the levels of VEGF mRNA expression tended to be higher in carcinomas of advanced stage than in early stage carcinomas. Both in situ mRNA hybridization and immunohistochemistry demonstrated the presence of VEGF expression within the tumor cells. These results suggest that VEGF may confer angiogenesis and progression of human gastric carcinomas, especially of the well-differentiated type.     

乙酰肝素酶、肝细胞生长因子和血管内皮生长因子在非小细胞肺癌组织中的表达及其相关性

目的:研究乙酰肝素酶(HPA)、肝细胞生长因子(HGF)、血管内皮生长因子(VEGF)在非小细胞肺癌(NSCLC)组织中的表达及其与临床特征之间的关系;并分析三者表达的相关性。方法:采用免疫组织化学检测45例非小细胞肺癌组织及10例正常组织中HPA、HGF及VEGF的表达水平。结果:非小细胞肺癌组织中HPA、VEGF的表达与正常组织表达、TNM分期有关。HGF的表达与正常组织的表达有关。三者中任意两者间在非小细胞肺癌组织中的表达均呈正相关性。结论:HPA、HGF与VEGF参与了非小细胞肺癌的发生、发展、浸润与转移;在非小细胞肺癌的发展过程中,三者之间可能存在协同作用。     

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.