VEGF及其受体KDR在垂体腺瘤中的表达与肿瘤血管形成的关系

 目的　探讨血管内皮生长因子(VEGF) 及其受体( KDR) 的表达与垂体腺瘤血管生成的关系。方法　应用免疫组织化学S2P 法检测58 例人垂体腺瘤中的V E GF 及KD R 的表达,并对血管进行染色、计数。结果　其中54 例有VEGF 的表达(占93. 1 %) ,阳性表达主要位于肿瘤细胞胞膜及胞浆; KD R 在47 例中有阳性表达(占81. 0 %) ,阳性表达位于肿瘤血管内皮细胞、肿瘤细胞胞膜及胞浆。VEGF 和KD R 表达与垂体腺瘤的侵袭性密切相关;V E GF 和KD R 高表达组微血管密度明显高于低表达组( P <0. 01) 。结论　VEGF 以旁分泌、自分泌形式协同KDR 促进垂体腺瘤血管的生成,并与垂体腺瘤的侵袭密切相关。     

胃癌中血管内皮生长因子的表达及其意义

目的探讨胃癌组织中血管内皮生长因子（Vascular endothelial growth factor,VEGF）的表达及其与临床病理学之间的关系。方法应用免疫组织化学方法检测55例胃癌组织、12例癌旁胃组织和正常胃组织中的VEGF蛋白的表达及微血管密度（MVD）。结果胃癌组织的VEGF阳性表达率为78．2％,主要集中于肿瘤细胞胞质内;胃癌组织中微血管分布不均,血管密集区主要集中在癌灶边缘。VEGF蛋白表达及MVD在胃癌组织中均显著高于癌旁胃组织及正常胃组织（P〈0．05）;胃癌中VEGF表达与浸润深度、淋巴结转移、病理分期、肿瘤分化程度密切相关（P〈0．05）,而与患者的性别、年龄、肿瘤直径无关（P〉0．05）。结论VEGF在胃癌的发生、发展中起重要作用,有望作为胃癌抗血管治疗的靶标。     

促血管生成素-2对胃癌血管生成的双向效应

目的　探讨促血管生成素 2 (Ang 2 )在胃癌血管生成中的作用。方法　运用RT PCR和S P免疫组化方法检测Ang 2mRNA、血管内皮生长因子 (VEGF)、CD34蛋白在 36例胃癌及其相应癌旁胃黏膜组织中的表达。结果　胃癌组织及其相应癌旁胃黏膜组织均见有Ang 2mRNA阳性表达 ,胃癌组织Ang 2mRNA的总体表达水平与微血管密度 (MVD)未见明显相关。胃癌组织Ang 2mRNA表达水平低于癌旁胃黏膜组织者 2 7例 ,其癌组织中 ,Ang 2mRNA的表达水平与MVD呈正相关 (r=0 .4 11,P <0 .0 5 ) ;同时 ,VEGF阳性表达者的MVD(45 .4 5± 10 .30 )明显高于VEGF阴性染色者 (30 .15± 8.6 9,P <0 .0 5 ) ,即在Ang 2表达上调的情况下VEGF促进血管生成。胃癌组织Ang 2mRNA表达水平高于癌旁组织者 9例 ,其癌组织中Ang 2mRNA的表达水平与肿瘤组织的MVD呈负相关 (r =- 0 .75 8,P <0 .0 5 ) ,VEGF的阳性表达者与阴性染色者间 ,MVD差异无显著性 ,即Ang 2抑制血管生成与VEGF的表达无相关性。结论　Ang 2对胃癌血管生成具有双向调节作用。     

血管内皮生长因子受体在骨巨细胞瘤中的表达及其与肿瘤增殖和血管生成关系的研究

目的 探讨血管内皮生长因子受体(KDR)在骨巨细胞瘤中的表达情况,及其与肿瘤血管生成和增殖状态的关系,并分析各种因素在骨GCT预后中的作用。方法 对58例患者之石蜡切片采用SP法检测VEGF/KDR、CD34及MIB-1的表达,同时收集临床及随访资料。分析VEGF、KDR与微血管密度(MVD)、增殖指数(PI)、临床因素及预后的关系。结果(1)骨GCT中新生血管主要位于肿瘤浸润边缘。VEGF阳性率为53.6％,KDR阳性率高达96.4％。(2)VEGF阳性组和KDR高表达组MVD均值分别高于VEGF阴性组和KDR低表达组(P<0.05)。VEGF/KDR与MVD呈正相关。KDR高表达组PI值高于KDR低表达组(P<0.05),二者呈正相关。VEGF与PI无显著相关性。(3)VEGF/KDR表达及MVD与PI与各临床因素无关(P>0.05)。(4)多因素logistic回归分析表明MVD、KDR以及手术方式与预后有关。KDR、MVD是影响其复发的危险因素。结论 VEGF及其受体与骨GCT的增殖和血管生成密切相关。VEGF能通过KDR以旁分泌或自分泌形式作用,间接或直接刺激肿瘤细胞增殖。MVD、KDR以及手术方式与预后有关,可作为判断患者预后的指标,并为骨GCT的抗血管生成治疗提供了实验依据。     

VEGF及其受体KDR在非小细胞肺癌中的表达及与肿瘤血管形成关系

目的：探讨血管内皮生长因子（VEGF）及其受体（KDR）的表达与非小细胞肺癌（NSCLC）血管形成的关系。方法：分别应用免疫组织化学S-P法和原位分子杂交法检测62例NSCLC组织和16例肺的良性瘤样病变组织中的VEGF和KDR mRNA的表达，并对血管进行染色、计数。结果：62例肺癌组织中46例有VEGF的表达（占74．29％），阳性表达位于肿瘤细胞胞膜及胞质；KDR mRNA在49例中有阳性表达（占79．03％），阳性表达位于肿瘤血管内皮细胞、肿瘤细胞胞膜及胞质。VEGF和KDR mRNA的表达与有无淋巴结转移和临床病理分期密切相关；VEGF和KDR mRNA阳性表达组微血管密度明显高于阴性表达组，P〈0．01。结论：VEGF和KDR的表达与NSCLC的发生、发展和转移可能密切相关，可作为评估NSCLC患者预后的一项指标。     

胃癌生长与血管内皮生长因子及受体有关

第四军医大学西京医院消化科刘都户博士等,近日完成的一项研究认为,胃癌的生长与血管内皮生长因子及其受体有关。刘都户博士在导师张学庸教授的指导下,采用免疫组织化学妞C法,对扣例人胃癌组织中的血管内皮生长因子及其受体的表达与分布进行研究。结果显示,50％的胃癌组织表达血管内皮生长因子,阳性物质主要位于肿瘤细胞膜及胞浆,受体染色阳性物质主要位于癌组织及癌组织旁的血管内皮细胞上。m、w期胃癌组织血管内皮生长因子的阳性率（分别为cd．67％、sl．82％）,均高于I、11期的胃癌组织（分别为20％、18．18％,P＜0．05）;不…     

促血管生成因子及受体在肝癌生长中的作用

目的　探讨不同的促血管生成分子及受体在肝癌血管生成中的作用。方法　收集临床切除的肝癌标本 15例 ,应用RP PCR和Westernblot方法检测肝癌标本中不同部位的血管内皮生长因子 (VEGF)及其受体 (KDR)和血管生成素 (Ang1、Ang2 )及其受体 (Tie2 )的表达。以免疫组织化学检测内皮细胞特异性的标志分子CD34,并且分析血管密度与促血管生成因子表达的关系。结果　在肝癌组织中 ,VEGF和Ang2的表达水平与其他部位比较 ,差异有显著性 (P <0 .0 1) ;血管的分布以癌组织及癌旁组织中密度最高。KDR、Ang1和Tie2的表达虽然在各部位间差异无显著性 ,但在癌组织和癌旁组织中的表达存在不同程度的升高。结论　在肝癌的生长过程中 ,VEGF/KDR和Angiopietins/Tie2两条通路均有不同程度的活化 ,但不协调 ,使得肝癌组织中的血管处于不成熟状态 ,这为进一步开发抑制血管生成的抗肿瘤生长药物提供了科学依据     

VEGF及其受体KDF在宫颈癌的联合表达与局部肿瘤血管生成的关系

目的:探讨血管内皮生长因子及其受体KDR在早期宫颈癌的表达及其对宫颈癌肿瘤血管生成的作用.方法:采用免疫组织化学SP法检测18例宫颈上皮内瘤样病变(cervical intraepithelial neoplasm,CIN)、75例早期宫颈癌(invasive carcinoma of cervix,ICC)和15例正常宫颈上皮(normal cervical epithelium,NCE)中VEGF和KDR的表达情况,并检测其中微血管密度(CD34标记).结果:在ICC中,VEGF和KDR主要表达于癌细胞膜和(或)细胞浆;而CD34主要表达于癌巢间质血管内皮细胞.从NCE到CIN再到ICC,VEGF与KDR的阳性表达率以及MVD均显著升高(P<0.01).在ICC中,VEGF、KDR阳性表达者其MVD分别显著高于VEGF、KDR阴性表达者(P＜0.05).VEGF在ICC的表达与KDR显著正相关(r=0.56,P<0.01),并且两者均与MVD显著正相关(前者r=0.60,P<0.01;后者r=0.33,P<0.01).VEGF与KDR均阳性表达者,其微血管密度显著高于两者均阴性表达者(P<0.01).结论:VEGF及其受体KDR表达在宫颈癌肿瘤血管生成中起上调作用,两者均过度表达,肿瘤血管生成显著增加.检测VEGF及其受体KDR的联合表达对进一步了解宫颈癌血管生成情况以及寻找抗肿瘤血管生成治疗新靶点有一定价值.     

血管内皮生长因子及其受体在喉鳞癌中的表达

目的探讨血管内皮生长因子（VEGF）及其受体Fit-1及KDR在喉鳞癌生长、转移过程中的作用及机制。方法采用Western—blotting法和RT-PCR法检测20例喉鳞癌组织及18例癌旁组织中VEGF、Fit-1及KDR的蛋白和mRNA的表达水平。结果VEGF、Fit—1及KDR蛋白和mRNA在喉鳞癌组织中的表达分别为4．32±2．21、2．00±0．91,1．20±0．55、0．29±0．31,2．50±1．69、0．85±0．28,差异有统计学意义（均P〈0．01）;VEGF、Flt-1及KDR蛋白和mRNA在颈淋巴结转移组与非颈淋巴结转移组差异有统计学意义（P〈0．01或P〈0．05）;VEGF与KDR在喉鳞癌及癌旁组织中的表达水平之间呈正相关（P〈0．01）,而VEGF与Flt-1在喉鳞癌组织中的表达水平之间则无相关性（P〉0．05）。结论VEGF及其受体Flt-1、KDR参与了喉鳞癌新生血管增生过程,与喉鳞癌的生长、浸润和淋巴结转移密切相关,KDR是喉鳞癌组织中VEGF发挥作用的重要受体。     

VEGF及其受体KDR在宫颈癌的联合表达与局部肿瘤血管生成的关系

目的:探讨血管内皮生长因子及其受体KDR在早期宫颈癌的表达及其对宫颈癌肿瘤血管生成的作用。方法:采用免疫组织化学SP法检测18例宫颈上皮内瘤样病变(cervicalintraepithelialneoplasm,CIN)、75例早期宫颈癌(invasivecarcinomaofcervix,ICC)和15例正常宫颈上皮(normalcervicalepithelium,NCE)中VEGF和KDR的表达情况,并检测其中微血管密度(CD34标记)。结果:在ICC中,VEGF和KDR主要表达于癌细胞膜和(或)细胞浆;而CD34主要表达于癌巢间质血管内皮细胞。从NCE到CIN再到ICC,VEGF与KDR的阳性表达率以及MVD均显著升高(P<0.01)。在ICC中,VEGF、KDR阳性表达者其MVD分别显著高于VEGF、KDR阴性表达者(P<0.05)。VEGF在ICC的表达与KDR显著正相关(r=0.56,P<0.01),并且两者均与MVD显著正相关(前者r=0.60,P<0.01;后者r=0.33,P<0.01)。VEGF与KDR均阳性表达者,其微血管密度显著高于两者均阴性表达者(P<0.01)。结论:VEGF及其受体KDR表达在宫颈癌肿瘤血管生成中起上调作用,两者均过度表达,肿瘤血管生成显著增加。检测VEGF及其受体KDR的联合表达对进一步了解宫颈癌血管生成情况以及寻找抗肿瘤血管生成治疗新靶点有一定价值。     

VEGF及其受体KDR在非小细胞肺癌中的表达及与肿瘤血管形成关系

目的:探讨血管内皮生长因子(VEGF)及其受体(KDR)的表达与非小细胞肺癌(NSCLC)血管形成的关系。方法:分别应用免疫组织化学S-P法和原位分子杂交法检测62例NSCLC组织和16例肺的良性瘤样病变组织中的VEGF和KDRmRNA的表达,并对血管进行染色、计数。结果:62例肺癌组织中46例有VEGF的表达(占74·29%),阳性表达位于肿瘤细胞胞膜及胞质;KDR mRNA在49例中有阳性表达(占79·03%),阳性表达位于肿瘤血管内皮细胞、肿瘤细胞胞膜及胞质。VEGF和KDR mRNA的表达与有无淋巴结转移和临床病理分期密切相关;VEGF和KDR mRNA阳性表达组微血管密度明显高于阴性表达组,P<0·01。结论:VEGF和KDR的表达与NSCLC的发生、发展和转移可能密切相关,可作为评估NSCLC患者预后的一项指标。     

VEGF receptor antisense therapy inhibits angiogenesis and peritoneal dissemination of human gastric cancer in nude mice

The efficacy of a phosphorothioate antisense oligonucleotide (ASO) for KDR/Flk-1 (KDR/Flk-1-ASO), an endothelial cell-specific vascular endothelial growth factor (VEGF) receptor, was investigated on the peritoneal dissemination and angiogenesis of a human gastric cancer cell line in nude mice. Green fluorescent protein (GFP)-transduced NUGC-4 (NUGC-4-GFP) human gastric cancer cells were implanted into the peritoneal cavity of nude mice. KDR/Flk-1-ASO, -SO, or phosphate-buffered saline was administrated from days 7 to 14, 200 microg/mouse, once a day. The mice were sacrificed on day 28. Disseminated peritoneal tumor nodules expressing GFP were visualized by fluorescence microscopy. KDR/Flk-1-ASO significantly decreased the extent of peritoneal dissemination of the tumors. The number of cells undergoing apoptosis was significantly increased in the KDR/Flk-1-ASO-treated tumors. Microvessel density was significantly reduced in the KDR/Flk-1-ASO-treated tumor nodules. The KDR/Flk-1 antisense strategy, therefore, decreases tumor dissemination apparently by inhibiting angiogenesis.     

Expression and localization of vascular endothelial growth factor receptors in human hepatocellular carcinoma and non-HCC tissues

Flt-1 (VEGF receptor-1) and KDR/Flk-1 (VEGF receptor-2) are the high-affinity receptors for the angiogenesis factor, vascular endothelial growth factor (VEGF). VEGF expression has been confirmed in human hepatocellular carcinoma (HCC), and VEGF is thought to be involved in the angiogenesis within HCC tissues. However, expressions of VEGF receptors in HCC have not been reported. We immunohistochemically examined expressions and localizations of Flt-1 and KDR in 28 surgically resected HCC tissues. In non-cancerous area, Flt-1 and KDR were mainly found in macrophages including Kupffer cells; both receptors were found in vascular endothelial cells in the portal veins and arteries within portal tracts; and KDR was also found in some sinusoidal endothelial cells. In cancerous area, Flt-1 and KDR were found in some macrophages, and also in the endothelial cells of intratumoral blood vessels. In 25 moderately and/or poorly differentiated HCCs, KDR expression in the blood space endothelial cells was clear and continuous in 20 cases, and focal in 5 cases. These results suggest that there would be an angiogenesis mechanism via VEGF/Flt-1 or VEGF/KDR in HCC, and the VEGF/KDR system would take a more important role.     

EGCG对胃癌血管新生中VEGF信号通路的多靶点作用

目的：探讨EGCG对胃癌血管生成抑制作用及其信号通路。方法：建立裸鼠异位胃癌模型,经腹腔注射EGCG,检测肿瘤生长及肿瘤组织微血管密度;不同浓度EGCG处理胃癌细胞24 h,检测胃癌VEGF蛋白和mRNA表达及VEGF分泌;同时不同浓度EGCG处理脐静脉内皮细胞,检测内皮细胞生长、迁移和体外小管形成。结果：EGCG显著抑制胃癌生长和肿瘤血管生成,平均肿瘤抑制率60.4%;EGCG显著抑制胃癌VEGF蛋白、mRNA表达和VEGF分泌;EGCG时间和剂量依赖性地抑制VEGF诱导的内皮细胞增殖,同时也剂量依赖性地抑制VEGF诱导的内皮细胞的迁移和小管生成。结论：EGCG多靶点作用于VEGF信号通路,抑制胃癌生长和血管生成。     

The effects of VEGF and VEGFR-2 on survival in patients with gastric cancer

Prognostic criteria of the patients with gastric cancer are of critical importance in their management and follow-up. Angiogenesis is essential for the growth and metastasis of solid tumors. Tumor angiogenesis is a multi-step interactive process, and vascular endothelial growth factor (VEGF) and its receptors have a major role in tumor angiogenesis. Thus, we investigated the effects of VEGF and VEGF receptor-2 (VEGFR-2, KDR) on survival in patients with gastric cancer. We analyzed 51 patients who had undergone total or subtotal gastric resection. The patients were divided into two subgroups according to their VEGF and VEGFR-2 (KDR) expression in resected specimens. There was no significant difference between sex, surgical method, lymph node metastasis, serosal invasion, hematogenous metastasis, chemotherapy status of the two subgroups. Mean follow-up time was 24.22 +/- 15.38 months. We found the survival rates of the patients with VEGF positive tumors to be significantly shorter than those of the patients with VEGF negative tumors. There was no significant difference between the survival rates of VEGFR-2 (KDR) positive and negative patients. It was established that the presence of VEGF expression was significantly associated with the short survival rates in patients with gastric cancer. Analysis of VEGF expression in resected specimens may provide additional guidance in determining the prognosis of such patients. If more extensive studies confirm the significance of VEGF and its receptors in gastric cancer, new therapeutic approaches targeting VEGF and its receptors may be considered in gastric cancer management.     

p53、血管内皮生长因子在大肠癌组织中的表达与血管生成

目的　探讨p53、血管内皮生长因子 (VEGF)在大肠癌组织中的表达及其与血管生成的关系。方法　利用免疫组化SABC法 ,对 1 0 6例大肠癌组织及 2 0例正常大肠组织中的 p53、VEGF的表达及微血管密度 (MVD)进行研究。 结果　p53、VEGF的表达与肿瘤的分化程度及Dukes分期无明显相关性 (P >0 .0 5 )。p53表达阳性或VEGF表达阳性的大肠癌组织MVD明显高于p53表达阴性 (P <0 .0 1 )或VEGF表达阴性者 (P <0 .0 1 )。p53表达阳性的大肠癌组织中VEGF的表达阳性率显著高于 p53表达阴性者 (P <0 .0 1 )。结论　p53、VEGF在大肠癌的发生和发展中起着重要作用 ,可反映大肠癌的恶性程度和进展情况并作为预后的指标 ,p53作用的发挥是通过上调VEGF的表达水平来实现的     

Relationship between Co-expression of Vascular Endothelial Growth Factor and its Receptor, Kinase Insert Domain Containing Receptor and Tumor Angiogenesis in Invasive Carcinoma of the Cervix

Objective The aim of the present study was to determine the expression of vascular endothelial growth factor (VEGF) and its receptor, kinase insert domain containing receptor (KDR), and their significance in regulating tumor angiogenesis in the early stages of cervical cancer. Methods Using the immunohistochemical SP method, the expression of VEGF and KDR was determined in the cancer cells. In addition, the microvessel density (MVD), labeled by CD34 in the tumor stroma, was examined in 18 cases of cervical intraepithelial neoplasms (CIN), 75 cases of early invasive cervix carcinomas (ICC) and 15 specimens of normal cervical epithelium (NCE). Results In ICC cases, VEGF and KDR were mainly expressed in the cellular membrane and/or cytoplasm of tumor cells, while expression of CD34 was found mainly in the vascular epithelial cells of the tumor stroma. The positive expression rate of VEGF and KDR, and the MVD increased remarkably from NCE through CIN to ICC (P< 0.01). For the ICC group, in the patients with positive expression of VEGF and KDR, the MVD was significantly higher than those with negative expression of VEGF and KDR (P<0.05). Expression of VEGF in ICC was positively related to KDR expression (r=0.56,P<0.01 ). The MVD was also positively related to both the expression of VEGF (r=0.60,P<0.01), and KDR (r=0.33,P<0.01). In the cases with both positive expression of VEGF and KDR, the MVD was significantly higher than those in which there was negative expression of both(P<0.01). Conclusion Expression of VEGF and its receptor KDR plays a key role in up-regulating tumor angiogenesis in cervical carcinoma. Co-overexpression of VEGF and KDR results in rapid tumor vasculogenesis. Detection of co-expression of VEGF and KDR may be of value in further understanding tumor angiogenesis and in searching for new targets for anti-angiogenesis therapy in invasive carcinoma of the cervix. This work was supported by the Department of Education of Fujian Province (No. 01B017).