血管内皮生长因子及其受体在白血病中的表达及作用

血管内皮生长因子(VEGF)及其受体的表达,在白血病细胞的增殖和存活中发挥了重要作用.几乎所有类型的白血病均可见VEGF及其受体的表达,VEGF及其受体与白血病的预后及分期等密切相关.     

血管内皮生长因子在急性白血病患者中表达的研究

目的:探讨血管内皮生长因子在急性白血病患者的表达及其与各临床病理特征的关系.方法:采用免疫组织化学的方法检测40例自愿急性白血病患者治疗前后骨髓细胞VEGF的表达.结果:VEGF在急性白血病患者中表达明显高于对照组,治疗后缓解组VEGF表达水平明显下降.有髓外转移组VEGF表达明显高于无髓外转移组.结论:急性白血病患者中存在VEGF高表达,可能与急性白血病的发病、转移及疾病的预后有关.     

血管内皮生长因子及其受体在急性髓系白血病骨髓细胞中的变化

用免疫组化方法对20例初治急性髓系白血病（AML）患儿化疗前后骨髓中血管内皮生长因子（VEGF）及其受体（VEGFR）的表达进行了研究。     

血管内皮生长因子及其受体与白血病的研究进展

血管新生 (ａｎｇｉｏｇｅｎｅｓｉｓ)是血管内皮细胞通过出芽方式形成新的血管的生理过程 ,该过程受到多种正负调控因子的严格调控 ,正调控因子包括血管内皮生长因子 (Ｖａｓｃｕｌａｒｅｎ ｄｏｔｈｅｌｉａｌｇｒｏｗｔｈｆａｃｔｏｒＶＥＧＦ)、成纤维细胞生长因子 (ｂＦＧ     

成人急性白血病患者细胞血管内皮生长因子及其受体FLT-1、KDR的表达

目的　探讨成人急性白血病 (AL )患者细胞血管内皮生长因子 (VEGF)及其受体 FL T- 1(fm s- like tyro-sine kinase)、KDR(kinase- dom ain insert containing receptor)的表达。方法　采用 RT- PCR方法检测骨髓单个核细胞 (BM MNCs) VEGF及其受体 FL T- 1、KDR m RNA的表达水平。结果　 (1)初发未治患者、骨髓缓解患者 (BMR)和正常对照者 BM MNCs VEGF m RNA阳性表达例数的差异无显著性 (P>0 .0 5 ) ,而 BM MNCs VEGF/β- actin相对表达量 ,在初发未治组显著高于 BMR组和正常对照组 (P值均 <0 .0 1) ,后两组之间的差异无显著性 (P>0 .0 5 ) ;AML组高于 AL L患者 (P<0 .0 5 )。 (2 )初发未治患者 BM MNCs FL T- 1、KDR m RNA阳性表达例数较 BMR及正常对照者高 (P值均 <0 .0 5 ) ,后两组之间的差异无显著性 (P>0 .0 5 ) ;AML组 BM MNCs KDR m RNA阳性表达例数高于 AL L组 (P<0 .0 5 ) ;应用 FL T- 1/β- actin、KDR/β- actin相对表达量分析与上述结果一致。 (3) BM MNCsVEGF的相对表达量与其受体 FL T- 1和 KDR的相对表达量呈相关性 (P值均 <0 .0 5 )。结论　 AL细胞 VEGF、FL T- 1和 KDR m RNA呈过表达 ;VEGF和 KDR m RNA表达强度 ,在 AML明显高于 AL L。应用半定量方法更能反映患者细胞 VEGF m RNA表达     

血管内皮生长因子在急性白血病患者中表达的研究

目的：探讨血管内皮生长因子在急性白血病患者的表达及其与各临床病理特征的关系。方法：采用免疫组织化学的方法检测40例自愿急性白血病患者治疗前后骨髓细胞VEGF的表达。结果：VEGF在急性白血病患者中表达明显高于对照组，治疗后缓解组VEGF表达水平明显下降。有髓外转移组VEGF表达明显高于无髓外转移组。结论：急性白血病患者中存在VEGF高表达，可能与急性白血病的发病、转移及疾病的预后有关。     

血管内皮生长因子-C在急性白血病中表达的意义

 目的　探讨血管内皮生长因子-C（VEGF-C）在急性白血病中的表达及其临床意义。方法　采用免疫细胞化学方法检测48例急性白血病患者及46例非白血病对照患者VEGF-C的表达水平。结果　急性白血病患者VEGF-C阳性率为45.9 %,明显高于对照组的2.2 %;两者差异有统计学意义（P＝0.000）;VEGF-C表达阴性组白血病患者化疗疗效明显优于阳性组患者（P＝0.036）。结论　VEGF-C与急性白血病的发病有关,并对其预后判断有重要的意义。     

血管内皮生长因子及其受体与白血病的关系

 血管内皮生长因子（vascular endothelial growth factor ,VEGF）是作用最强,特异性最高的血管新生调节因子,研究表明,白血病细胞不仅高表达VEGF,而且不同程度的表达VEGF受体,VEGF 与白血病的发生、发展相关,影响白血病的预后。研究VEGF 与白血病的关系,为白血病的抗血管增生治疗提供依据。     

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。     

卵巢肿瘤组织中血管内皮生长因子及其受体表达与临床病理的关系

目的:探讨卵巢肿瘤组织中VEGF表达及其受体与临床病理的关系。方法:对54例卵巢恶性肿瘤、14例卵巢良性肿瘤和16例正常卵巢组织采用免疫组织化学方法测定其VEGF及受体蛋白表达,并分析与临床病理的关系。结果:1)恶性肿瘤组织中VEGF及其受体蛋白表达阳性率明显高于良性肿瘤和正常卵巢组织,均有显著性差异(P<0.01)。2)恶性肿瘤内的VEGF表达阳性率与临床分期无明显相关(P>0.05)。但VEGF受体蛋白表达阳性率在晚期患者组织中明显高于早期患者(P<0.05)。3)VEGF受体表达阳性与其患者的腹水量、大网膜转移和盆腹腔淋巴结转移阳性呈正相关(P<0.05)。4)恶性肿瘤组织中VEGF及其受体蛋白共表达阳性者的平均总生存期明显低于不表达者。Kaplan-Meier生存曲线分析显示,二者累积生存率有显著性差异(P<0.05)。结论:恶性肿瘤组织中的VEGF及其受体蛋白阳性表达明显增高,其受体表达与患者的临床分期、腹水量、大网膜和盆腹腔淋巴结转移相关,VEGF及其受体蛋白共表达为卵巢癌患者的不良预后。     

肺癌血管内皮生长因子(VEGF)及其受体KDR、Flt1的表达与患者预后的关系

背景与目的 血管内皮生长因子（VEGF）及其受体与肺癌血管生成关系密切，但与肺癌患者预后的关系尚不明确。本研究的目的是对VEGF及其受体KDR、Flt1的表达与肺癌患者预后的关系进行探讨。方法 应用免疫组织化学PV-9000法检测75例具有完整随访资料的肺癌标本中VEGF及其受体KDR、Flt1的表达。结果 VEGF、KDR、Flt1在肺癌组织中的表达较为广泛，主要位于肿瘤细胞、血管内皮细胞、纤维母细胞胞质中，且其表达呈异质性，肺癌组织周边部及坏死区周围的肺癌细胞中表达较强，三者在肿瘤细胞中的阳性率均高于间质纤维母细胞（P〈0．01，P〈0．02，P〈0．02）。肺癌细胞及纤维母细胞VEGF、KDR和Flt1的阳性表达率在术后不同生存时间的三组间差异均具统计学意义（P〈0．01，P〈0．01，P〈0．01；P〈0．01，P〈0．01，P〈0．05）；肺癌细胞VEGF、KDR、Flt1阳性组患者的生存时间均显著低于各相应指标阴性者（P〈0．0001，P〈0．0005，P〈0．0005）。肺癌细胞中VEGF与Flt1受体的表达呈正相关（P〈0．01），纤维母细胞中VEGF与肺癌细胞中Flt1受体的表达呈正相关（P〈0．01），纤维母细胞中VEGF与KDR、Flt1表达分别呈正相关（P〈0．01，P〈0．01）。结论 VEGF可能是促进肺癌细胞生长的重要因子，主要以自分泌途径并附以旁分泌途径通过Flt1发挥作用；VEGF及受体KDR、Flt1对肺癌患者的预后有重要的影响作用。     

血管内皮细胞生长因子影响难治性急性髓系白血病发生发展的作用研究

背景和目的:难治性白血病的发生发展机制非常复杂,近年来发现白血病患者骨髓过度表达血管内皮细胞生长因子(vascularendothelialgrowthfactor,VEGF),但VEGF如何影响难治性白血病尚未明确。本研究探讨高表达VEGF对人急性髓系白血病细胞株HL-60增殖及三尖杉酯碱诱导HL-60细胞凋亡影响;观察难治性急性髓系白血病(acutemyeloidleukemia,AML)中VEGF蛋白表达与疾病发展的相关性。方法:采用脂质体转染VEGF165cDNA入HL-60细胞,通过RT-PCR及ELISA方法鉴定转染克隆HL-60/VEGF165细胞中VEGFmRNA及蛋白的表达,MTT法、集落形成实验比较HL-60/VEGF165及转染pcDNA3.1-neo空载体的HL-60/neo细胞增殖活性,流式细胞仪观察三尖杉酯碱诱导的细胞凋亡。用ELISA法检测难治性与非难治性AML患者血浆中VEGF蛋白浓度。结果:HL-60/VEGF165细胞培养上清中VEGF蛋白浓度为(399.07±12.45)ng/L,高于HL-60/neo细胞(184.45±10.53)ng/L(P<0.01)。HL-60/VEGF165细胞与HL-60/neo细胞相比生长速度明显加快,集落形成能力明显增加,集落数分别为(157.00±17.00)/500细胞和(110.00±12.90)/500细胞(P<0.05);而细胞凋亡率减少,分别为(3.18±0.33)%和(6.61±0.50)%,三尖杉酯碱诱导HL-60/VEGF165细胞凋亡率低于HL-60/neo细胞。难治性AML患者血浆中VE     

Overexpression of vascular endothelial growth factor (VEGF) and its cellular receptor KDR (VEGFR-2) in the bone marrow of patients with acute myeloid leukemia.

Vascular endothelial growth factor (VEGF) and its cellular receptor VEGFR-2 have been implicated as the main endothelial pathway required for tumor neovascularization. However, the importance of the VEGF/VEGFR-2 system for angiogenesis in hematologic malignancies such as AML remains to be elucidated. In 32 patients with newly diagnosed untreated AML, we observed by immunohistochemical analysis of bone marrow biopsies significantly higher levels of VEGF and VEGFR-2 expression than in 10 control patients (P <0.001). In contrast, VEGFR-1 staining levels in AML patients were in the same range as in the controls. Expression of VEGF and VEGFR-2 was significantly higher in patients with a high degree of microvessel density compared to those with a low degree (VEGF: P =0.024; VEGFR-2: P =0.040) and correlated well with bone marrow microvessel density (r(s)=0.566 and 0.609, respectively; P <0.001). Furthermore, in patients who achieved a complete remission following induction chemotherapy VEGFR-2 staining levels decreased into the normal range. In conclusion, our results provide evidence for increased expression of VEGF/VEGFR-2 of leukemic blasts and correlation with angiogenesis in the bone marrow of AML patients. Thus, VEGF/VEGFR-2 might constitute promising targets for antiangiogenic and antileukemic treatment strategies in AML.     

VEGF及其受体Flt和KDR水平变化与胶质瘤关系及临床意义

 目的 探讨胶质瘤患者血清血管内皮生长因子（VEGF）及其受体Flt-1和KDR水平变化，为评价胶质瘤治疗效果，判断预后寻找一种科学的生物学标志物。方法 收集治疗前后胶质瘤患者、脑转移癌患者和健康对照者血清，进行VEGF，Flt-1和KDR水平的检测，SPSS11.5统计软件包对数据进行t检验和相关分析。结果 （1）治疗前脑胶质瘤和脑转移瘤患者血清VEGF水平明显高于健康对照组； 脑胶质瘤患者组和脑转移瘤患者组血清Flt-1水平明显高于健康对照组；脑胶质瘤患者组血清KDR水平明显高于健康对照组； 治疗后缓解的胶质瘤患者组VEGF和Flt-1水平明显低于治疗前。差异均有统计学意义。（2） VEGF与Flt-1和KDR有显著的相关性。结论 胶质瘤患者血清中VEGF及其受体的检测，可作为胶质瘤辅助诊断、治疗效果监测和预后判断的重要生物学指标。     

Increased expression of vascular endothelial growth factor (VEGF) in bone marrow of patients with myeloproliferative disorders (MPD)

Angiogenesis is a multistep process of the development of capillaries from established blood vessels. Angiogenesis probably plays a significant role in the development and progression of hematopoietic malignancies. Higher microvascular density and increased serum levels of proangiogenic factors such as vascular endothelial growth factor (VEGF) or basic fibroblasts growth factor (bFGF) have been reported in acute and chronic leukemias, myeloproliferative and myelodysplastic disorders, multiple myeloma and lymphomas. The microvessel density of bone marrow stroma in myeloproliferative disorders is increased and VEGF is considered as the most potent endothelial cell activator. The purpose of this study was to examine the expression of VEGF in bone marrow of patients with MPD. 60 paraffinembedded bone marrow core biopsy specimens from newly diagnosed patients with MPD were evaluated. In addition 10 bone marrow core biopsy specimens from adult patients without evidence of malignancy were used as controls. Bone marrow sections were stained immunohistochemically for VEGF (PharMingen, USA). Obtained data show that MPD are associated with an increased expression of VEGF in the bone marrow. This observation support previous studies suggesting that angiogenesis may play a role in the pathophysiology of myeloproliferative disorders. Clinical significance of this phenomenon needs further investigation however thus provides rationale for use of angiogenesis inhibitors in MPD therapy.     

血管内皮生长因子及其受体与骨肉瘤关系的研究进展

血管内皮生长因子（ＶＥＧＦ）是一种序列高度保守、高度特异性的促血管内皮细胞生长因子,广泛分布于人和动物体内的大脑、肾脏、肝脏、脾脏、胰腺和骨骼等组织中,对内皮细胞具有强烈的促有丝分裂作用,刺激血管内皮细胞增殖和血管通透性增加,促进新生血管形成。ＶＥＧＦ通过与血管内皮细胞表面受体（ＶＥＧＦＲ）特异性结合发挥生物学效应。抑制ＶＥＧＦ及ＶＥＧＦＲ的活性可以减缓或阻滞骨肉瘤侵袭和转移。研究表明,ＶＥＧＦ及ＶＥＧＦＲ对肿瘤血管及淋巴管的生成及肿瘤侵袭和转移起重要作用。本文对ＶＥＧＦ及ＶＥＧＦＲ与骨肉瘤血管与淋巴管生成及其侵袭与转移的关系作一综述。     

急性淋巴细胞白血病患者血清ＶＥＧＦ及Ｓｕｒｖｉｖｉｎ的测定及其临床意义

目的：检测血清血管内皮细胞生长因子（ＶＥＧＦ）和凋亡存活蛋白（Ｓｕｒｖｉｖｉｎ）在急性淋巴细胞白血病（ＡＬＬ）患者中的含量变化并探讨其临床意义。方法：应用双抗体夹心酶联免疫吸附法检测５３例ＡＬＬ患者血清ＶＥＧＦ及Ｓｕｒｖｉｖｉｎ在化疗前后含量的变化。结果：与正常成人对照组相比,初治组在化疗前血清ＶＥＧＦ、Ｓｕｒｖｉｖｉｎ含量明显增高,差异均有统计学意义（Ｐ＜０.０１）。未缓解组化疗前血清ＶＥＧＦ及Ｓｕｒｖｉｖｉｎ的含量与完全缓解组化疗前和对照组相比明显升高,差异均有统计学意义（Ｐ＜０.０１）,化疗后血清ＶＥＧＦ和Ｓｕｒｖｉｖｉｎ的含量无明显下降,但均明显高于完全缓解组化疗后（Ｐ＜０.０１）。ＡＬＬ初治患者化疗前血清ＶＥＧＦ与Ｓｕｒｖｉｖｉｎ含量呈正相关（ｒ＝０.５０,Ｐ＜０.０１）。结论：ＶＥＧＦ及Ｓｕｒｖｉｖｉｎ在ＡＬＬ的发病中具有重要作用,可作为了解病情、观察疗效和判断预后的指标之一。     

Co-expression of vascular endothelial growth factor (VEGF) and its receptors (flk-1 and flt-1) in hormone-induced mammary cancer in the Noble rat

Vascular endothelial growth factor (VEGF) is recognized to play a predominant role in breast cancer prognosis. The action of VEGF is mediated by two high-affinity receptors with ligand-stimulated tyrosine kinase activity: VEGFR-1/flt-1 and VEGFR-2/flk-1, which are expressed mainly in vascular endothelial cells. To the best of our knowledge, no previous studies on the expression of these receptors in breast cancer cells has been made. We have established a new animal model for breast cancer, using a combination of 17beta-oestradiol and testosterone as 'carcinogens'. Taking advantage of the animal model, we have demonstrated that mammary cancer cells expressed not only high levels of VEGF but also, surprisingly, its receptors (fit-1 and flk-1) in mammary cancer cells. Intense reactivities to VEGF, flt-1 and flk-1 were observed in mammary cancer cells, especially in invasive mammary carcinoma. Western blot analysis confirmed the increase in flk-1 and flt-1 proteins in induced mammary cancers. Based on these observations, we hypothesize that in mammary cancer, VEGF regulates, in addition to endothelial proliferation and angiogenesis, also growth of cancer cells by an autocrine mechanism mediated through its receptors. To further verify this hypothesis, we investigated the correlation between cellular proliferation and the expression of VEGF, flt-1 and flk-1. Using double-labelling immunocytochemistry, we have shown a correlation between high VEGF activity and Ki-67 expression. The Ki-67 indices in the areas of strong and weak VEGF reactivities were 58.3% and 3.7% respectively. Similarly, there was also a correlation of strong flk-1 and Ki-67 reactivity. The Ki-67 indices for areas of strong and weak flk-1 reactivities were 53.9% and 3.1% respectively. On the other hand, there was a reverse correlation between fit-1 and Ki-67 activities. These results indicate that overexpression of VEGF and flk-1 is correlated with high Ki-67 index. The data, therefore, suggest that VEGF may act as an autocrine growth factor for mammary cancer cells in vivo and this autocrine regulatory role may be mediated through flk-1. The present study is the first report showing that VEGF may act as a growth stimulator for mammary cancer cells.