SCCA、FIB和VEGF水平在宫颈鳞癌中表达水平和病理分期的相关性分析

目的 探讨鳞状细胞癌抗原(squamous cell carcinoma antigen, SCCA)、纤维蛋白原(fibrinogen,FIB)和血管内皮生长因子(vascular endothelial growth factor,VEGF)水平在宫颈鳞癌中表达水平变化.方法 2018年1月—2019年12月期间收...     

VEGF蛋白表达及VEGF-2578C/A等位基因频率与非小细胞肺癌临床特征、预后的关系

目的 探讨血管内皮生长因子(vascular endothelial growth factor,VEGF)蛋白表达及VEGF-2578C/A等位基因频率与非小细胞肺癌(non-small cell lung cancer,NSCLC)临床特征、预后的关系.方法 纳入中国人民解放军海军安庆医院2018年3月-2020年...     

宫颈鳞癌中血管内皮生长因子-C、血管内皮生长因子受体-3的表达与人乳头瘤病毒16/18感染的相关性分析

目的 分析宫颈鳞癌中血管内皮生长因子(vascular endothelial growth factor,VEGF)-C、VEGF受体(VEGF receptor,VEGFR)-3的表达与人乳头瘤病毒(human papillomavirus,HPV)16/18感染的相关性.方法 收集2017年3月至2019年3月德...     

血管内皮生长因子及其受体在胃癌研究中的进展

血管内皮生长因子（vascular endothelial growth factor,VEGF）又称血管通秀因子（vascular permeability factor,VPF）是1989年由Connolly等发现并命名的一种糖蛋白,为血管生成的主要调控因子,通过与内皮细胞表面上的特异性受体结合而发挥其生物学活性.随着对VEGF研究的不断深入,在肿瘤诊疗中的应用日趋受到临床重视.本文就VEGF及其受体在胃癌研究中的进展概述如下.     

血管内皮生长因子与卵巢癌临床病理联系的研究进展

血管内皮生长因子(vascular endothelial growth factor,VEGF)在多种实体肿瘤的发生发展中都发挥着重要的作用.近年对卵巢癌血清VEGF的研究已取得了长足的进步.为卵巢癌的早期诊断、治疗及预后评价提供了新的思路.     

血管内皮生长因子在肿瘤血管形成中的作用及其靶向治疗研究进展

肿瘤发展依赖于组织周围新生血管的形成。在众多促进血管生成的内源性因子中,血管内皮生长因子(vascular endothelial growth factor,VEGF)发挥了关键性作用,因此,以VEGF为靶点进行抗肿瘤血管生成成为抗癌治疗的重要策略。截至目前,大量靶向VEGF信号转导系统的抗血管生成药物已应用于临床或处于临床试验阶段,包括VEGF单克隆抗体、VEGF受体激酶抑制剂及作用于其下游信号通路的小分子抑制剂等。本文针对VEGF的信号转导系统及其靶向治疗现状予以综述,并简要阐述抗肿瘤血管生成治疗过程中耐药现象的产生机制。     

血管内皮生长因子及其受体与妇科肿瘤

血管内皮生长因子(vascular endothelial growth factor, VEGF)及其受体通过刺激血管内皮细胞分裂增生形成新生血管而促进肿瘤细胞生长、侵袭和转移.如何对其进一步研究来为临床肿瘤诊断与治疗提供一定的帮助已成为近年来肿瘤研究领域的热点之一.本文就两者与妇科肿瘤的发病关系进行综述.     

甘草素对人脐静脉内皮细胞血管生成的作用及其机制探讨

目的研究甘草素(liquirigenin,LQ)对人脐静脉内皮细胞(HUVECs)血管生成的作用及其分子机制。方法采用四甲基氮唑兰MTT比色法检测甘草素对HUVEC细胞增殖的影响;划痕试验观察甘草素对细胞迁移的影响;蛋白质印迹法分析甘草素对血管生成相关蛋白和通路的影响。结果甘草素可抑制HUVEC细胞增殖,75μmol/L时,存活率为76.8%;甘草素可降低HUVEC细胞的迁移能力,随剂量浓度增加,细胞迁移能力减弱;甘草素可阻断磷脂酰肌醇3-激酶/蛋白激酶B/p70S6激酶(PI3K/AKT/p70S6K)信号通路,并下调血管内皮生长因子(vascular endothelial growth factor,VEGF)和缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)蛋白的表达。结论甘草素抑制人脐静脉内皮细胞增殖和迁移,并可经PI3K/AKT/p70S6K信号通路介导抑制血管生成靶向因子VEGF和HIF-1α的表达。     

血管内皮生长因子及其在心血管疾病中的研究进展

血管内皮生长因子(vascular endothelial growth factor,VEGF)是由Ferrara和Henzel[1]于1989年从培养的牛垂体滤泡星状细胞中分离出的一种多肽,具有特异性促血管内皮细胞增殖分裂、促进新生血管形成和侧支循环开放等作用.由于其众多的生理、病理作用而被人们广泛研究,尤其在心血管和外周血管疾病、肾脏疾病以及肿瘤等领域颇受关注.现就VEGF的生物学特点及其在常见心血管疾病中的研究进展作一综述.     

染料木黄酮对MDA-MB-453乳腺癌细胞uPA表达及PTK活性的影响研究

目的: 观察染料木黄酮(亦称三羟异黄酮,genistein,Gen)对MDA-MB-453乳腺癌细胞尿激酶型纤维蛋白溶酶原激活剂(urokinase-type plasminogen activator,uPA)表达及蛋白酪氨酸激酶(protein tyrosine kinase,PTK)活性的影响,探讨Gen抗HER-2/neu高表达乳腺癌血管生成的分子机制。方法: 5×10-5mol/L Gen处理MDA-MB-453细胞24、48、72 h后,应用Western blot、免疫沉淀、RT-PCR及激酶活性分析法检测Gen对MDA-MB-453乳腺癌细胞uPA表达、HER-2/neu受体蛋白磷酸化水平及PTK活性变化。结果: Gen处理MDA-MB-453细胞后,uPA的mRNA和蛋白表达量下调,HER-2/neu受体蛋白磷酸化水平降低,PTK活性下降,且这种作用具有时效性。结论: Gen能有效抑制乳腺癌细胞HER-2/neu受体的PTK活性和蛋白磷酸化水平,在转录和翻译水平下调uPA的表达,从而抑制HER-2/neu高表达乳腺癌血管生成。     

染料木黄酮对MDA-MB-453乳腺癌细胞VEGF表达的影响

目的:观察染料木黄酮(genistein,Gen)对MDA-MB-453乳腺癌细胞血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)表达的影响,探讨Gen抗HER-2/neu高表达乳腺癌血管生成的分子机制。方法:5×10-5mol/LGen处理MDA-MB-453细胞24、48、72h后,应用免疫组织化学、Westernblot及RT-PCR法检测MDA-MB-453乳腺癌细胞VEGF的表达变化。结果:Gen处理MDA-MB-453细胞24、48、72h后,VEGF的mRNA和蛋白表达量随着处理时间的延长逐渐下降。结论:Gen能在转录和翻译水平下调HER-2/neu高表达乳腺癌细胞VEGF的表达,这可能是Gen抑制HER-2/neu高表达乳腺癌血管生成的机制之一。     

环境雌激素对大鼠乳腺癌VEGF和CXCR4影响

目的 研究环境雌激素辛基酚(OP)和三羟异黄酮(GEN)对大鼠乳腺癌中血管内皮生长因子(VEGF)及其受体(flk-1)和血小板源性因子受体-4(CXCR4)表达的影响.方法 雌性SD大鼠随机分为对照组(Con)、模型组(Mod)及3个实验组:GEN、OP和GP(GEN+OP).二甲基苯蒽启动致乳腺癌(Con组除外),第210d处死大鼠,用免疫组化和免疫印迹检测大鼠乳腺及乳腺癌组织中VEGF、flk-1和CXCR4表达.结果 与Mod组比较,GEN组VEGF、flk-1和CXCR4蛋白表达均降低,OP组VEGF、flk-1和CXCR4表达增高,GP组CXCR4降低.结论 GEN通过下调乳腺癌组织中VEGF、flk-1和CXCR4的表达量,降低大鼠乳腺癌的发生,OP则通过上调VEGF、flk-1和CXCR4的表达使乳腺癌的发生率增加.     

染料木黄酮对脂多糖诱导的RAW264.7细胞炎症因子、腺苷酸激活蛋白激酶磷酸化的影响

目的研究染料木黄酮(genistein,Gen)对脂多糖(LPS)诱导的巨噬细胞炎症因子产生和腺苷酸激活蛋白激酶(AMPK)磷酸化的影响。方法体外培养RAW 264.7小鼠单核巨噬细胞,加入1、5、10、50、100 mol/L的Gen共同培养,MTT法检测其对细胞活性的影响。将RAW264.7细胞随机分为4组:空白对照组不加任何药物,模型组加入终浓度为1 g/ml的LPS进行刺激,Gen高、低剂量组分别加入终浓度为10、5 mol/L的Gen预处理1h后,再加入终浓度为1 g/ml的LPS刺激,24h后收取细胞上清用酶联免疫(ELISA)方法检测TNF-α、IL-6含量,Westernblot检测AMPKα蛋白及其磷酸化的表达水平。结果 100 mol/L的Gen对体外培养RAW264.7细胞的增殖有影响,而其他浓度则无。LPS处理的RAW 264.7细胞与对照组比较,TNF-α、IL-6生成显著增多(P<0.01)、AMPKα磷酸化水平显著降低(P<0.01),而AMPKα总蛋白表达水平无差异(P>0.05)。Gen干预可减少LPS诱导的TNF-α、IL-6生成,上调AMPKα磷酸化水平的表达,与LPS组相比,差异均有统计学意义(P<0.01)。结论 Gen能抑制LPS诱导巨噬细胞的炎症反应,减少TNF-α、IL-6生成,这可能与Gen促进AMPKα磷酸化,从而激活AMPKα有关。     

Pro-Apoptotic and Anti-Angiogenesis Effects of Olive Leaf Extract on Spontaneous Mouse Mammary Tumor Model by Balancing Vascular Endothelial Growth Factor and Endostatin Levels

It has been proven that olive associated products such as olive leaf extract (OLE) causes significant reduction in cancer cells viability and proliferation. Female BALB/c adult mice were divided into four groups. Three days prior to oral treatments, tumors were transplanted. First group were treated with distilled water and other three groups were received, respectively, 75, 150, and 225?mg/kg/day of OLE for three weeks. For assessment of anti-angiogenesis and pro-apoptotic effect of OLE on tumor tissue, tumor volume, cell mitosis and apoptosis, and also vascular endothelial growth factor (VEGF) and endostatin levels were assessed. OLE treatment with 150 and 225?mg/kg/day lead to significant reduction in tumor volume and cell mitosis compared with the control group, while the same doses significantly increase tumor cell apoptosis. OLE treatment with 150?mg/kg/day increase endostatin levels, while the same dose did not significantly decrease VEGF levels. The VEGF level is significantly reduced by the treatment with OLE 225?mg/kg/day for three?weeks. Although, further studies are needed to clarify anti-angiogenesis and anti-apoptotic mechanism of OLE, consumption of OLE polyphenols after tumor transplantation reduced spontaneous mouse mammary tumor growth.     

Mechanisms of action and antiproliferative properties of Brassica oleracea juice in human breast cancer cell lines

Cruciferous vegetables are an important source of compounds that may be useful for chemoprevention. In this study, we evaluated the antiproliferative activity of juice obtained from leaves of several varieties of Brassica oleracea on both estrogen receptor (ER)-positive (ER+; MCF-7 and BT474) and ER-negative (ER-; MDA-MB-231 and BT20) human breast cancer cell lines. The effect of juice on cell proliferation was evaluated on DNA synthesis and on cell cycle-related proteins. Juice markedly reduced DNA synthesis, evaluated by [3H]thymidine incorporation, starting from low concentrations (final concentration 5-15 mL/L), and this activity was independent of ER. All cauliflower varieties tested suppressed cell proliferation in a dose-dependent manner. Cell growth inhibition was accompanied by significant cell death at the higher juice concentrations, although no evidence of apoptosis was found. Interestingly, the juice displayed a preferential activity against breast cancer cells compared with other mammalian cell lines investigated (ECV304, VERO, Hep2, 3T3, and MCF-10A) (P < 0.01). At the molecular level, the inhibition of proliferation was associated with significantly reduced CDK6 expression and an increased level of p27 in ER+ cells but not in ER- cells, whereas a common feature in all cell lines was significantly decreased retinoblastoma protein phosphorylation. These results suggest that the edible part of Brassica oleracea contains substances that can markedly inhibit the growth of both ER+ and ER- human breast cancer cells, although through different mechanisms. These results suggest that the widely available cruciferous vegetables are potential chemopreventive agents.     

香烟烟雾提取物对MIN6细胞JNK及p38MAPK表达影响

目的 探讨体外香烟烟雾提取物（CSE）对胰岛MIN6细胞形态及活力的影响,及对胞内丝裂原活化蛋白激酶（MAPKs）信号转导通路ERK、JNK、p38MAPK表达的影响。方法 体外培养MIN6细胞至生长对数期后,设不同浓度CSE（20、50、100和200 μg/mL）实验组,同时设对照组,48 h后,镜下观察MIN6细胞形态学改变,并应用CCK-8法检测CSE对MIN6细胞的增殖抑制率;同时应用蛋白印迹法（WB）检测细胞内ERK、JNK、p38MAPK蛋白及磷酸化程度。结果 与对照组比较,100和200 μg/mL剂量下的细胞形态出现明显异常,胞核固缩,细胞呈梭形样改变;与对照组比较,MIN6细胞活力出现下降,20、50、100、200 μg/mL各组细胞活力分别为（97.32±2.67）%、（94.67±5.33）%、（87.71±12.3）%和（74.23±25.8）%;与对照组相比,ERK、JNK、p38MAPK蛋白表达变化不大,但随着CSE剂量的增加,p-JNK和p-p38MAPK磷酸化程度明显增加（与对照组相比,P<0.05）,并呈一定的剂量-效应关系。结论 CSE能够导致MIN6细胞形态异常、抑制其细胞增殖活力,其机制可能与JNK和p38MAPK信号通路的激活相关。     

In vitro effects of soy phytoestrogens on rat L6 skeletal muscle cells

Soy isoflavones display estrogenic activity in humans and animals, and thus are referred to as phytoestrogens. This study was performed to observe the effects of the soy isoflavones genistein, daidzein, and glycitein on cell cultures of rat skeletal muscles. [3H]Thymidine incorporation was used to determine cell proliferation, while protein synthesis and degradation were determined by tracking radiolabeled leucine. For the proliferation studies, insulin, estradiol, genistein, daidzein, or glycitein was supplemented at 0, 0.04, 0.08, 0.16, 0.31, 0.63, 1.25, 2.5, 5, 10, or 20 microM, respectively, or in combinations with final concentrations of 0, 0.1, 1, or 10 microM. Genistein reacted most similarly to estradiol, inhibiting proliferation at > or = 1 microM (P < .001). A combination of phytoestrogens resulted in significant inhibition of cell proliferation, but not to the extent observed with genistein alone. For the protein synthesis and degradation experiments, treatments of 0.1 microM dexamethasone or 1 microM concentrations of insulin, genistein, daidzein, or glycitein were used. Phytoestrogens did not inhibit or stimulate protein degradation or synthesis (P > .05). A one-tailed univariate analysis of variance revealed a trend (P < or = .1) in protein stimulation with genistein and glycitein treatments. These results suggest that the tyrosine kinase inhibiting activity of genistein may be affecting phosphorylation of the mitosis-promoting factor, preventing the advancement of the mitotic cell cycle. In addition, at higher total combined concentrations, daidzein and glycitein may be able to outcompete genistein for receptor sites. These results suggest that soy isoflavones in the diet may potentially modulate normal growth and development in humans and animals that ingest soy-based products.     

黄芪对高糖环境下细胞膜流动性影响

目的 探讨黄芪注射液(RA)对高糖环境下ECV304细胞膜流动性的影响,为RA在糖尿病治疗中的应用提供实验依据。方法 体外实验中利用葡萄糖建立高糖环境,体外培养ECV304细胞,将细胞随机分为正常组、高糖组、黄芪保护组(RA)组和甘露醇高渗对照组(简称甘露醇组)。加入处理因素24 h后,收集细胞,测定各组细胞的细胞膜流动性和各组细胞产生OH,O₂^-、和丙二醛(MDA)水平。结果 高糖组细胞产生MDA水平明显升高,显著高于正常组、RA组和甘露醇组细胞(P<0.01);RA组细胞产生MDA水平显著低于甘露醇组(P<0.01),与正常组细胞比较,差异无统计学意义。高糖组细胞抑制OH、O₂^-的能力显著低于正常组、RA组和甘露醇组细胞(P<0.01);RA组细胞抑制OH、O₂^-的能力显著高于甘露醇组细胞(P<0.01),与正常组细胞比较,差异无统计学意义。高糖组细胞超氧化物歧化酶(SOD)活性显著低于正常组、RA组和甘露醇组细胞(P<0.01);RA细胞SOD活性与正常组细胞比较,差异无统计学意义。RA组细胞的细胞膜流动性显著高于高糖组细胞(P<0.01),与正常组细胞比较,差异无统计学意义。结论 黄芪通过抗氧化作用,可保护高糖环境下ECV 304细胞的细胞膜流动性。     

重组人内皮抑素的表达纯化及对内皮细胞增殖的影响

目的探讨融合表达的重组人内皮抑素对人脐带静脉血管内皮细胞（ECV304）增殖的影响。方法将pTRX—endo质粒转化大肠杆菌BL21（DE3）,IPTG诱导表达,经纯化后加入ECV304细胞培养,MTT法检测对内皮细胞增殖的影响。结果经SDS—PAGE分析,出现特异性蛋白质条带,纯化后得到纯度在95％以上的重组人内皮抑素蛋白,明显抑制ECV304的增殖。结论内皮抑素可明显抑制内皮细胞增殖,存在剂量效应关系,本实验为探索内皮抑素抑制血管生成的机制及应用研究打下基础。