血管内皮生长因子和碱性成纤维细胞生长因子在急性白血病患儿血清中的表达及意义

目的:探讨血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子( bFGF)急性白血病(AL)患儿血清中的表达及其与临床意义.方法:采用ELISA方法检测40例初治AL患儿化疗前及治疗1疗程后37例患儿和40例健康儿童血清中VEGF和bFGF的水平.结果:治疗前,AL组以及ALL组、ANLL组血清VEGF和bFGF水平均显著高于对照组(P＜0.05),而血清VEGF和bFGF水平在AL不同类型之间差异无统计学意义(P＞0.05).治疗前,AL缓解(CR)和未缓解(NR)患儿血清VEGF和bFGF水平差异无统计学意义;治疗后,CR患儿血清VEGF和bFGF水平显著下降,与治疗前和NR患儿比较均有显著性差异(P＜0.05);而NR患儿治疗前后血清VEGF和bFGF水平差异无统计学意义.结论:VEGF和bFGF在AL患儿血清中呈高表达,血清VEGF和bFGF水平可作为AL患儿疗效观察指标,并且与患儿的预后有关.     

碱性成纤维细胞生长因子的生物活性分析

本文报告以人脐带内皮细胞原代培养技术,CAM及多聚物载体技术检测bFGF生物活性,结果表明bFGF是机体血管新生的强烈刺激剂。bFGF对血管、神经、结缔组织、骨与软骨细胞具有多向作用,深入研究其生物效应,对于促血管新生,动脉硬化及肿瘤防治,中枢神经创伤后修复,肢体再生,晶体再生,促创伤愈合,以及人工血管的开发应用等均具有重要的实际意义。     

碱性成纤维细胞生长因子缓释体系诱导脂肪移植体早期血运重建

背景：脂肪移植吸收及其不可预测性直接影响该技术的临床应用,利用各种细胞因子来促进脂肪移植体早期血运重建,从而减少移植体吸收的技术在目前也有待提高。效果不稳定在于这些细胞因子在术后随血液和渗出液的流失而不能在较长时间内有效作用于血管内皮细胞。 目的：探讨碱性成纤维细胞生长因子与葡聚糖颗粒形成缓释体对脂肪移植体早期血运重建的影响。 方法：制备2 mg/L的碱性成纤维细胞生长因子溶液及其同浓度的碱性成纤维细胞生长因子-葡聚糖缓释颗粒。SD大鼠12只取腹股沟脂肪行自体脂肪移植,左侧背部皮下植入脂肪珠加入重组型碱性成纤维细胞生长因子溶液(对照组),右侧背部皮下植入脂肪珠加碱性成纤维细胞生长因子-葡聚糖缓释颗粒(缓释组),在7,14 d随机方法处死动物各1只,用墨汁灌注微血管显像法观察移植体内部和包膜血管早期生成密度。移植后90 d,将剩余大鼠处死,取移植体测量体积。 结果与结论：在植入后7,14 d,包膜和移植体内血管计数缓释组均高于对照组(P < 0.01)。90 d后缓释组移植体的体积大于对照组(P < 0.05)。碱性成纤维细胞生长因子缓释体可以更好地促进脂肪移植体早期血运重建。实验结果说明,碱性成纤维细胞生长因子缓释体有利于减少术后脂肪移植体的吸收。     

碱性成纤维细胞生长因子对移植的胚胎脊髓组织存活与生长的影响

用胚胎脊髓腹侧组织块植入缺损运动神经元的大鼠脊髓内；同时把带有神经的拇长伸肌移放到脊髓移植物旁，其神经的断端插入移植的部位。应用碱性成纤维细胞生长因子作用脊髓移植物，经ＨＲＰ逆行追踪、乙酰胆碱酯酶和琥珀酸脱氢酶组化染色等方法显示：碱性成纤维细胞生长因子对移植的胚胎脊髓神经元的存活与生长有促进作用。     

碱性成纤维细胞生长因子促进大鼠随意皮瓣成活的实验 …

目的：研究碱性成纤维细胞生长因子（ｂＦＧＦ）对促进大比例超长随意皮瓣成活的作用。方法：采用大鼠背部随意皮瓣动物模型，自身对照，于术后第一天实验组一次性局部应用ｂＧＦＧ４００ＩＵ。应用ＲＰＭ＾２镭射多普勒血流仪数字温度计对随意皮瓣的成活进行动态监测，并结合墨汁注制作透明标本进行形态学观察。结果：实验组皮瓣成秒同于对照组（Ｐ〈０．０５）；血流值从术后第二天实验组皮瓣末端显著高于对照组（Ｐ〈０．０５，Ｐ     

VEGF基因转染脂肪干细胞后上清液对皮肤成纤维细胞及脐静脉血管内皮细胞的影响

目的:通过慢病毒将血管内皮生长因子(VEGF)基因转染于人脂肪干细胞(HADSCs),检测其上清液(CM)中生长因子的表达,并用其上清液作用于人皮肤成纤维细胞(HDFs)及人脐静脉内皮细胞(HUVECs),观察对这2种细胞活力和迁移的影响。方法:准备HADSCs、HDFs及HUVECs 3种细胞并鉴定;将携带VEGF165基因的慢病毒转染于HADSCs,定时收集上清液;ELISA法检验上清中生长因子分泌情况;将VEGF-CM与完全培养液以一定比例混合分为5组,分别培养HDFs及HUVECs,CCK-8法检验对2种细胞活力的影响;将最佳比例的VEGF-CM、正常CM(Nor-CM)和完全培养液分别作用于HDFs及HUVECs,划痕法测试出对2种细胞迁移的影响。结果:ELISA结果表明VEGF-CM中VEGF及碱性成纤维细胞生长因子(bFGF)的表达均较Nor-CM组提高;相对于其它比例,当完全培养液与VEGF-CM以1∶2的比例混合时,HDFs和HUVECs的活力显著增强(P0.05);VEGF-CM与其它培养液相比可显著提高HDFs和HUVECs的迁移能力(P0.05)。结论:转染VEGF165基因后的HADSCs可同时增强VEGF及bFGF的分泌,其上清液可提高成纤维细胞及血管内皮细胞的活力和迁移能力。     

碱性成纤维细胞生长因子与卵巢癌的关系

目的　探讨碱性成纤维细胞生长因子 (basic fibroblast growth factor,b FGF)对卵巢癌细胞增殖、浸润和肿瘤血管生成的影响 ,及 b FGF单克隆抗体 (b FGF monoclonal antibody,b FGF- MAb)的治疗作用。　方法　将人卵巢癌细胞株 SKOV3接种于 2 4孔板 ,加入不同浓度的 b FGF,每日行结晶紫染色后测定光密度 (D4 90 )值 ,绘制细胞生长曲线 ;将 SKOV3细胞团接种于铺设有细胞外基质凝胶的 4孔板 ,每日测定癌细胞在凝胶中的浸润距离 ;建立 SKOV3细胞裸鼠皮下移植瘤模型 ,每周两次分别将 b FGF、b FGF-MAb和生理盐水注射于移植瘤周围 ,8周后测量肿瘤体积 ;对移植瘤组织切片行 因子的免疫组化染色、测定肿瘤内微血管密度 (microvessel density,MVD)。　结果　 b FGF能促进 SKOV3细胞增殖并呈浓度依赖 ,实验第 5天 ,5 ng/ml、10 ng/ml组细胞 D4 90 值是对照组的 1.0 9倍和 1.2 1倍 ;b FGF能促进 SKOV3细胞浸润并呈浓度依赖 (P<0 .0 5 ) ,第 7天 ,5 ng/ml、10 ng/ml组细胞浸润距离分别是对照组的 1.5 3倍和2 .4 5倍 ;b FGF组移植瘤体积和 MVD分别是对照组的 1.80倍和 1.4 6倍 (P<0 .0 5 ) ,b FGF- MAb组移植瘤体积和 MVD分别是对照组的 6 3.7%和 6 2 .8% (P<0 .0 5 )。　结论　b FGF能明显促进卵巢癌细胞的增殖、     

碱性成纤维细胞生长因子对瘢痕成纤维细胞生物学行为的影响

目的探讨碱性成纤维细胞生长因子（bFGF）对瘢痕成纤维细胞生物学特性的影响。方法采用细胞培养、MTT、ELISA法、氯胺T和RT—PCR法检测bFGF在不同作用剂量下对瘢痕来源的成纤维细胞生长增殖和细胞外基质（ECM）合成的影响。结果（1）MTT检测bFGF对瘢痕成纤维细胞有明确的促增殖作用，并具有剂量相关性；（2）氯胺T法显示实验组和对照组HPr含量无显著性差异，RT—PCR法显示各组Ⅰ、Ⅲ型胶原蛋白mRNA表达水平无明显变化；说明bFGF对瘢痕成纤维细胞胶原蛋白的合成无促进作用；（3）ELISA法表明随着bFGF作用浓度的升高，FN的表达表现为增高趋势，且以100ng／ml浓度下作用最显著。结论bFGF可以促进创面愈合，但不引起瘢痕的过度形成。     

碱性成纤维细胞生长因子的研究进展

bFGF是一种作用广泛的细胞因子，其最显著的作用是促进细胞分裂，因此在肿瘤的发生发展、促进损伤组织修复等方面受到关注。除了通过经典的受体途径发挥作用外，高分子量bFGF还具有核转位现象，其核转位只发生在G1-S过渡期。应用酵母双杂交系统发现了能与bFGF发生相互作用的蛋白质，为研究bFGF作用的分子机制提供了有益的线索。     

碱性成纤维细胞生长因子的基础与应用研究

碱性成纤维细胞生长因子（ｂＦＧＦ）是一个促有丝分裂的蛋白质分子，是ＦＧＦ家族中最具代表性的成员。它具有高亲合力和低亲合力两类受体，以极微的含量正常存在哺乳动物和人体的中枢神经组织和外周其他组织中，对中胚层和神经外胚层来源的组织细胞有很强的促生长作用。当炎症或外伤时，浸润的巨噬细胞和受损伤的细胞可以释放以ｂＦＧＦ为主的细胞生长因子以促进创伤的修复。而ｂＦＧＦ广谱的神经营养活性将为多种神经系统疾病的治疗提供理论依据。     

Expression of vascular endothelial growth factor and basic fibroblast growth factor in extramammary Paget disease

Extramammary Paget’s disease (EMPD) is a special type of cancers. The etiology of the disease is still unclear. We aimed to study the expression differences of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in EMPD tissues and corresponding adjacent normal tissues. The mRNA expression was detected by RT-PCR and the protein expression was explored by immunohistochemistry. Higher immunostaining signal scores of bFGF and VEGF in EMPD tissues had been found (z = -3.827, P < 0.001, z = -3.729, P < 0.001, respectively). In addition, the mRNA expression of bFGF and VEGF was higher in EMPD tissues, which had been validated by RT-PCR (t = 5.771, P < 0.001, t = 3.304, P = 0.004, respectively). The VEGF and bFGF might be the key signaling proteins in angiogenesis of EMPD. How to block the VEGF and bFGF in EMPD and to destroy the blood supply of the tumor cells becomes the focus of our future research.     

Plasma concentrations of vascular endothelial growth factor and basic fibroblast growth factor in lymphoproliferative disorders

Angiogenesis plays a major role in the development and progression of haematological malignancies. In our study we measured plasma concentrations of key angiogenic activators vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) using comercially available sandwich enzyme-linked immunosorbent assay (ELISA) in 37 patients with lymphoid malignancies and 20 healthy donors. We found a statistically significant increase in bFGF concentrations in patients with B-cell chronic lymphocytic leukemia (B-CLL, n=18) compared to the control group (median 118.8 vs. 9.3 pg/ml, p<0.001). However, we didn't find any significant difference in VEGF concentrations between B-CLL patients and the control group. There was also no significant increase in bFGF or VEGF in patients with multiple myeloma (n=7) and non-Hodgkin's lymphoma (n=12). Our pilot study shows that measurement of angiogenic activators in plasma is a feasible and reproducible method of angiogenesis assessment. Larger studies are needed for correlation between serum and plasma concentrations and detailed statistical evaluation including the impact on patients' survival.     

Localization of basic fibroblast growth factor and vascular endothelial growth factor in human glial neoplasms.

Fibroblast growth factors (FGFs) are widely recognized as a family of molecules that can influence cell proliferation and tissue neovascularization. Although the basic form of FGF (bFGF) has been found to enhance the growth of primary cell cultures made from human glial tumors, its exact role in vivo has been unclear. Likewise, vascular endothelial growth factor (VEGF) is a newly discovered addition to the growing list of angiogenic factors but, unlike bFGF, VEGF has a unique specificity for endothelial cells and possesses the properties required for secretion. In this study, we localized both basic FGF and VEGF in human gliomas to assess their possible role in the pathogenesis of these neoplasms. Retrospective analysis was performed using glial neoplasms that were fixed in 10% neutral buffered formalin and embedded in paraffin. The immunocytochemical procedures were performed using specific polyclonal antibodies raised against the amino terminus of bFGF and VEGF, respectively. Immunoreactive (IR) basic FGF was localized in normal, reactive, and neoplastic astrocytes as well as selected populations of normal neurons. IR VEGF, in contrast, was present primarily in neurons of normal brain, but was also found in both reactive and neoplastic astrocytes. In adjacent 4-microns tissue sections, strong immunoreactivity for VEGF and bFGF was found within the same populations of cells. In areas of endothelial proliferation, the strongest immunoreactivity for both growth factors was found within large anaplastic astrocytes that surrounded abnormal blood vessels. Our data support the hypothesis that VEGF may complement the actions of basic FGF in glial neoplasia.     

Coexpression of heparanase, basic fibroblast growth factor and vascular endothelial growth factor in human esophageal carcinomas

Heparan sulfate (HS), which is degraded by heparanase, plays an important role in cell adhesion, insolubility of the extracellular matrix (ECM) and as a reservoir for various growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). In the present study, we examined the immunohistochemical expression of heparanase, bFGF and VEGF, and evaluated the correlation between their expression and microvessel density (MVD) in human esophageal carcinomas. Heparanase, bFGF and VEGF were immunolocalized predominantly to the carcinoma cells, but they were also localized to the endothelial cells of microvessels near the carcinoma cell nests. In carcinomas with invasion of the muscular layer or adventitia, heparanase staining was stronger at the invasive areas of carcinomas than the intraepithelial spread. Expression of heparanase and bFGF and the degree of MVD were associated with tumor invasion, lymph node metastasis and pathological stages. Cases with positive staining for heparanase, bFGF or VEGF tended to have a higher MVD than those without staining, and carcinomas with concomitant expression of heparanase, bFGF and VEGF showed the highest MVD. The level of heparanase mRNA expression was directly correlated with the MVD. In addition, heparanase-positive cases had a higher positive ratio of bFGF and VEGF compared with the heparanase-negative cases. These data suggest the possibility that heparanase may contribute to not only cancer cell invasion but also angiogenesis probably through degradation of HS in the ECM and release of bFGF and VEGF from the HS-containing ECM.     

人脐带血内皮祖细胞与血管内皮生长因子和碱性成纤维细胞生长因子共培养及其增殖和迁移能力

背景：目前组织工程心脏瓣膜再内皮化种子细胞主要来源于成熟内皮细胞,内皮祖细胞作为内皮细胞的前体细胞越来越受到人们的关注。 目的：分离和扩增人脐带血内皮祖细胞,观测其体外生物学特性。 方法：密度梯度离心法分离新鲜的脐血中单个核细胞,在含血管内皮生长因子和碱性成纤维细胞生长因子的培养液中培养扩增,通过形态学、免疫荧光和流式细胞仪等对贴壁细胞进行鉴定;并与脐静脉内皮细胞进行增殖和迁移能力比较。 结果与结论：随着培养和诱导时间延长,贴壁细胞形态发生明显的改变,从小圆形变成梭形,逐渐分化成典型成熟内皮细胞的鹅卵石样形态,并可形成特征性的克隆;体外诱导7 d后90%以上贴壁细胞呈Dil-ac-LDL和FITC-UEA-I双阳性;贴壁细胞流式细胞仪分析显示：培养7 d的细胞VEGFR-2、CD34和CD133表达分别占(77.4±4.9)%、(52.4±6.6)%和(19.4±2.1)%,培养28 d的细胞VEGFR-2和CD34表达分别占(81.1±7.4)%和(7.6±3.1)%,而未检测到CD133表达;人内皮祖细胞增殖和迁移能力明显高于人脐静脉内皮细胞(P < 0.05),并且细胞数量可扩增达10⁹ L^-1。结果显示用密度梯度离心法和贴壁筛选法,可从人脐带血分离、纯化内皮祖细胞;内皮祖细胞可诱导分化为内皮细胞,增殖和迁移能力都很强。     

Intramyocardial injection of low-dose basic fibroblast growth factor or vascular endothelial growth factor induces angiogenesis in the infarcted rabbit myocardium.

BACKGROUND: Myocardial angiogenesis after the systemic administration of basic fibroblast growth factor or vascular endothelial growth factor at high therapeutic doses has been implicated in the occurrence of side effects that may undermine their safety. The aim of this study was to investigate the angiogenic effects of the intramyocardial administration of recombinant human basic fibroblast growth factor or vascular endothelial growth factor protein, at low doses, in the infarcted rabbit myocardium. METHODS AND RESULTS: Twenty-five New Zealand White rabbits were divided into five groups (n=5) and subjected to coronary artery ligation after lateral thoracotomy, inducing acute myocardial infarction. Five minutes later, the following substances were injected intramyocardially into the infarcted area: (a) normal saline (controls); (b) 6.25 or 12.5 mug of recombinant human basic fibroblast growth factor protein (basic fibroblast growth factor-1 group or basic fibroblast growth factor-2 group); or (c) 5 or 10 microg of recombinant human vascular endothelial growth factor 165 protein (vascular endothelial growth factor-1 group or vascular endothelial growth factor-2 group). On the 21st postoperative day, the animals were euthanized, and their hearts were subjected to histopathological examination and immunohistochemical assessment of vascular density in the infarcted area. The alkaline phosphatase anti-alkaline phosphatase procedure and the primary monoclonal antibody JC70 were used. Histopathological examination confirmed the induction of myocardial infarction. Vascular density was significantly increased (P<.004) in all treatment groups (in mean+/-S.E. vessels/x 200 optical field: basic fibroblast growth factor-1: 85.8+/-10.9; basic fibroblast growth factor-2: 76.6+/-3.7; vascular endothelial growth factor-1: 73.4+/-3.2; vascular endothelial growth factor-2: 89.5+/-5.2) compared to that in controls (58.9+/-4.9 vessels/x 200 optical field). Vascular density in the vascular endothelial growth factor-2 group was significantly higher than that in the vascular endothelial growth factor-1 group (P<.001). CONCLUSIONS: Low doses of recombinant human basic fibroblast growth factor or vascular endothelial growth factor protein, when administered intramyocardially, stimulate angiogenesis in the infarcted myocardium.     

碱性成纤维细胞生长因子共聚物缓释微球与兔跨区轴型皮瓣的成活

背景：研究表明使用生长因子直接或间接刺激新生血管形成可以促进皮瓣远端缺血部分的成活。 目的：观察碱性成纤维细胞生长因子-聚乳酸-聚羟基乙酸共聚物缓释微球对家兔侧腹制作跨区轴型皮瓣成活的影响。 方法：取24只健康家兔制作侧腹壁跨区轴型皮瓣,随机分组：实验组术前5 d皮内注入碱性成纤维细胞生长因子-聚乳酸-聚羟基乙酸共聚物微球,对照组术前5 d皮内注入碱性成纤维细胞生长因子+空微球悬浊液,空白对照组术前5 d皮内注入生理盐水。5 d后掀起皮瓣原位缝合。 结果与结论：①皮瓣成活率：实验组显著高于对照组和空白对照组(P < 0.01),②皮瓣组织学变化：实验组新生血管增生明显,以毛细血管为主。③CD34+免疫组织化学结果：实验组新生血管大量形成,平均血管数目高于对照组和空白对照组(P < 0.05)。表明术前5 d局部注射碱性成纤维细胞生长因子-聚乳酸-聚羟基乙酸共聚物缓释球可促进皮瓣新生血管形成,增加皮瓣血运,促进皮瓣成活。     

生物可降解聚合物结合碱性成纤维细胞生长因子与内皮细胞的黏附

背景：可降解材料的应用是体外构建小口径组织工程血管的重要研究部分。如何对可降解材料进行改性,以利于材料本身体外抗凝与促进内皮细胞黏附,是目前血管组织工程研究的热点之一。 目的：利用可降解聚己内酯接枝肝素材料体外负载碱性成纤维细胞生长因子,观察其对于内皮细胞黏附的影响。 方法：应用聚己内酯可降解材料,将肝素活化后并与聚己内酯的端羟基发生酯化反应从而被锚定在聚己内酯两端。经过电纺丝技术,制备血管支架。同时利用肝素和生长因子间的静电吸附作用,使支架负载碱性成纤维细胞生长因子。采用低密度内皮细胞短期静态种植,观察负载细胞生长因子的可降解聚己内酯材料对内皮细胞生长黏附情况的影响。 结果与结论：成功地制备了负载成纤维细胞生长因子的可降解聚己内酯接枝肝素支架。内皮黏附实验证实,该支架利于内皮细胞黏附。提示可降解聚己内酯接枝肝素材料负荷碱性细胞生长因子支架对内皮细胞有很好的体外黏附性。     

Bovine lactoferricin inhibits basic fibroblast growth factor- and vascular endothelial growth factor165-induced angiogenesis by competing for heparin-like binding sites on endothelial cells

Angiogenesis is a complex process whereby new blood vessels form from pre-existing vasculature in response to proangiogenic factors such as basic fibroblast growth factor (bFGF) and the 165-kd isoform of vascular endothelial growth factor (VEGF165). Angiogenesis inhibitors show considerable potential in the treatment of cancer because angiogenesis is necessary for tumor growth beyond a few millimeters in diameter because of the tumor's need for oxygen and nutrient supply, as well as waste removal. Bovine lactoferricin (LfcinB) is a peptide fragment of iron- and heparin-binding lactoferrin obtained from cow's milk. Here we provide in vivo and in vitro evidence that LfcinB has potent antiangiogenic activity. LfcinB strongly inhibited both bFGF- and VEGF165-induced angiogenesis in Matrigel plugs implanted in C57BL/6 mice. In addition, LfcinB inhibited the in vitro proliferation and migration of human umbilical vein endothelial cells (HUVECs) in response to bFGF or VEGF165 but was not cytotoxic to HUVECs. Rather, LfcinB complexed with heparin-like structures on the HUVEC surface that are involved in the binding of bFGF and VEGF165 to their respective receptors, thereby preventing receptor-stimulated angiogenesis. These findings suggest that LfcinB may have utility as an antiangiogenic agent for the treatment of human cancers.     

Importance of vascular phenotype by basic fibroblast growth factor, and influence of the angiogenic factors basic fibroblast growth factor/fibroblast growth factor receptor-1 and ephrin-A1/EphA2 on melanoma progression

The expression of several angiogenic factors and receptors was examined in a series of vertical growth phase cutaneous melanomas using high-throughput tissue microarray technology and immunohistochemistry. The results were correlated with microvessel density, clinicopathological features, and patient survival. Expression of basic fibroblast growth factor (bFGF) was significantly associated with increased microvessel density. Also, we found an independent prognostic importance of vascular phenotype by endothelial cell expression of bFGF; cases with positive vessels had the best prognosis and these tumors revealed a low frequency of vascular invasion (14%) when compared with bFGF-negative vessels (47%). This bFGF-negative phenotype was significantly increased in metastatic lesions. Strong tumor cell expression of FLT-4, ephrin-A1, and EphA2 was associated with increased melanoma thickness, and ephrin-A1 staining was related to decreased survival (P = 0.039). Expression of EphA2 in tumor cells was associated with increased tumor cell proliferation (Ki-67 positivity), indicating possible autocrine growth stimulation. Thus, our findings indicate the presence of phenotypic diversity among tumor-associated vessels, and subgroups defined by bFGF expression may be of clinical importance. bFGF was associated with microvessel density, whereas the ephrin-A1/EphA2 pathway might also be important for tumor cell proliferation and patient survival.