血管内皮生长因子和垂体瘤

原癌基因活化导致基因突变而引发肿瘤细胞的发生,各类原癌基因通过各种途径诱导血管生成相关因子诸如血管内皮生长因子(VEGF)、碱性纤维母细胞生长因子(bFGF)、转化生长因子(TEF)等的高度表达,而进一步促进肿瘤的生长。VEGF是肿瘤组织中促血管生成最主要的血管生长因子,目前发现二十余种以上生长因子作用于血管内皮,其中许多生长因子是通过     

基于血管生成的VEGFR酪氨酸激酶抑制剂的研究进展

血管内皮生长因子受体（VEGFR）是新生血管生成中的关键性促血管生长因子,VEGFR的异常活动会导致一些疾病的发生,例如癌症。本文针对血管生成与血管内皮生长因子受体（VEGFR）的关系以及近年来文献报道的血管内皮生长因子受体（VEGFR）抑制剂按其结构类别进行综述。     

VEGF受体酪氨酸激酶抑制剂的研究进展

肿瘤的生长和侵袭、转移依赖于新生血管的形成.抑制肿瘤介导的血管生成,阻断癌细胞的营养途径,就可有效抑制癌细胞增殖.血管内皮生长因子(VEGF)是肿瘤新生血管形成中的关键性促血管生长因子,它与特异性高表达在新生血管内皮细胞表面的受体酪氨酸激酶结合,激活酪氨酸激酶从而发挥生物学功能.因而以VEGF受体酪氨酸激酶为靶点的肿瘤血管靶向性治疗已成为近几年肿瘤治疗的新途径[1-3].     

VEGF、BFGF在肝海绵状血管瘤中的表达及意义

目的：检测VEGF及bFGF在肝海棉状血管瘤（CHL）中的表达，探讨CHL的生长机制。方法：CHL30例，CHL瘤旁正常肝组织10例，VEGF及bEFGF的检测采用免疫组化S-P法。结果：VEGF、BFGF阳性表达于CHL血窦内皮细胞浆，阳性率分别为46.7%和56.7%，而瘤旁正常肝组织中未见表达。结论：CHL生长可能与VEGF和BFGF有关。     

VEGF165_b的抗血管生成作用在肾癌发生、发展中的研究进展

肾癌是一种高度血管化的恶性实性肿瘤,其生长和转移依赖于新生血管的形成,而血管形成主要是由促血管生成因子和抑制因子调控失衡、促血管生成因子增多所致。血管内皮生长因子(VEGF)亚型VEGF165是机体内含量最多,生物活性最强的促血管生成因子,且在肾癌组织中高表达,与肿瘤的生长、转移密切相关。最新研究发现一种新的VEGF异构体VEGF165b具有抑制VEGF165介导的血管生成作用,有可能成为肾癌治疗过程中新的作用靶点,具有重要的临床应用价值。本文对VEGF165b的结构、作用机制进行综述。     

靶向血小板源生长因子受体酪氨酸激酶抑制剂的临床研究进展

随着血小板源生长因子(platelet-derived growth factor,PDCF)及其受体(platelet-derived growth factor receptor,PDGFR)在抗肿瘤作用中研究的深入,通过阻断PDGF/PDGFR信号转导通路来抑制肿瘤的生长,为治疗肿瘤提供了新的方法和策略。本文对进入临床研究的PDGFR激酶抑制剂的研究进展作一综述。     

VEGFR酪氨酸激酶抑制剂的临床应用与研究进展

血管内皮生长因子（ VEGF ）可诱导肿瘤的血管新生,在肿瘤生长中起到了关键作用。抑制血管内皮生长因子受体（ VEGFR）酪氨酸激酶能在一定程度上抑制肿瘤的生长, VEGFR酪氨酸激酶抑制剂已成为现在研究的热点之一。该文对VEGF和VEGFR进行了简要介绍,并简述了VEGFR酪氨酸激酶抑制剂的临床应用和主要化学结构类型。     

抗血管生成剂Aflibercept

异常的血管生成被认为是某些疾病,如癌症和湿性老年性黄斑变性（AMD）的病理基础,而抑制血管生成的最有效方法之一就是靶向阻断血管内皮生长因子（VEGF）信号通路,包括直接靶向VEGF、     

血管内皮生长因子与肿瘤的抗血管生成治疗

血管生成在肿瘤的生长和转移过程中起重要作用，肿瘤血管生成研究是近年来的热点，抗肿瘤血管生成治疗是目前探讨治疗肿瘤的新策略之一。在众多的肿瘤血管生成因子当中，血管内皮生长因子（vascular endothelial growth factor，VEGF）家族是最重要的一员。     

蛋白酪氨酸激酶抑制剂的进展与临床评价

目的：归结于药学和生物工程技术的进步,把对肿瘤细胞的攻击锁定于表皮生长因子和血管内皮生长因子等靶位,使药物治疗的切入点由细胞水平向分子水平过度,提高肿瘤联合治疗的效果,成为肿瘤综合治疗策略。由此应运而生蛋白酪氨酸激酶抑制剂独树一帜,对其研究和评价日趋活跃,本文总结其作用优势和临床评价。方法：采用国内、外文献综述方法。结果及结论：酪氨酸激酶抑制剂疗效确切、特异性强、不良反应和耐药性小,无疑是药学研究领域中的巨大突破。     

Nintedanib for the treatment of idiopathic pulmonary fibrosis

Introduction: Idiopathic Pulmonary Fibrosis (IPF) is an interstitial lung disease characterized by the progressive loss of pulmonary function, ultimately leading to respiratory failure and death. Two novel compounds, nintedanib and pirfenidone, have shown efficacy in reducing the rate of decline of lung function in IPF patients. The multiple tyrosine kinase inhibitor nintedanib has extensively being studied as a potential angiogenesis inhibitor in clinical against various neoplastic disorders. Afterwards, this compound was successfully tested in IPF.

Areas covered: Herein, the authors review the working mechanisms of nintedanib, its pharmacological profile, and its efficacy and safety for patients with IPF.

Expert opinion: Nintedanib has shown to be safe and effective in patients with IPF, with a favorable long-term safety profile. There is a lack of comparative trials of pirfenidone and nintedanib, and the choice of treatment is left to the physicians’ judgement. Future directions of nintedanib use are represented by the treatment of progressive fibrosing interstitial lung disease other than IPF, IPF with advanced functional impairment, and lung fibrosis secondary to connective tissue diseases. A promising safety profile for the combinational use of nintedanib and pirfenidone in IPF has also recently emerged.     

Nintedanib for the treatment of non-small-cell lung cancer

Introduction: In NSCLC, increased microvessel count, often used as a measure of angiogenesis, has been correlated with poor prognosis and associated with advanced disease and inferior outcomes. In the clinical development of antiangiogenic therapies, two approaches have been used; the first has been to inhibit ligand binding and receptor activation using targeted antibodies, whereas the second has been to inhibit receptor activation using tyrosine kinase inhibitors that target VEGF receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and/or fibroblast growth factor receptor (FGFR). Nintedanib is a triple angiokinase inhibitor that simultaneously acts on VEGFR, PDGFR and FGFR. It has shown significant antiangiogenic and antineoplastic activities in vitro, in preventing tumor growth and overcoming drug resistance.

Areas covered: Medline search was used with the following keywords: non-small-cell lung cancer and nintedanib or BIBF 1120, ASCO abstracts 2013 with nintedanib, and Phase I and Phase II abstracts lung cancer and nintedanib.

Expert opinion: Recent Phase III trials have shown promising efficacy results of nintedanib in NSCLC; however, many questions still need to be answered before it is put into routine use.     

BIBF 1120/nintedanib: a new triple angiokinase inhibitor-directed therapy in patients with non-small cell lung cancer

Introduction: Several new targeted agents with anti-angiogenic properties have been developed recently, including vandetanib, sunitinib, sorafenib, bevacizumab and others. Tumor development, progression, metastasis are strongly linked to angiogenesis. Targeted agents like bevacizumab, a monoclonal antibody which targets VEGF, have been fully developed in several solid tumors. These new agents strongly advocate that targeting angiogenesis is one of the best approaches for cancer therapy.

Areas covered: Those agents that target additional pro-angiogenic intracellular signaling pathways beyond VEGF signaling have also the potential to contribute to anticancer therapies. The authors present here nintedanib (BIBF 1120), a triple angiokinase inhibitor. It targets not only VEGFRs, but also FGFR and PDGFR. All the available clinical information regarding Phase I – II trials and the toxicity and efficacy of BIBF 1120 both as single agent and in combination with cytotoxic agents in non-small cell lung cancer (NSCLC) is reviewed and discussed here.

Expert opinion: Up till now, Phase I and II trials with nintedanib showed an improvement for survival of advanced NSCLC patients. Tolerability profile seems to be acceptable in these clinical trials. However, Phase III trials are mandatory to translate these findings into clinical practice. The research for predictive biomarkers could improve the success of these anti-angiogenic agents.     

特发性肺纤维化治疗药物的研究进展

特发性肺纤维化(IPF)是一种不可逆、进展性、致死性的慢性肺纤维化疾病,其进展较快,存活率较低,缺乏有效诊疗手段和治疗药物。近年来随着对其发病机制的了解,IPF治疗药物的开发也取得了一定进展。全球新批准并上市的治疗药物有吡非尼酮和尼达尼布,处于研发I、II期的有10多种,另外也有一些曾经有希望但已经不推荐用于IPF治疗的药物。     

特发性肺纤维化药物治疗进展

目的:介绍治疗特发性肺纤维化的药物及进展。方法:查询近几年国内外关于特发性肺纤维化药物治疗文献并进行分析。结果和结论:治疗特发性肺纤维化的药物有糖皮质激素+N-乙酰半胱氨酸+硫唑嘌呤、单用N-乙酰半胱氨酸、抗凝药物等,但均被随机临床对照试验(RCT)所否定,近年出现的新药吡非尼酮、尼达尼布可以改善患者肺功能下降速度,延缓疾病进展,但仍不能阻止疾病进展。     

Pirfenidone for the treatment of idiopathic pulmonary fibrosis

Although multidrug therapy is required in order to achieve good blood pressure control in many hypertensives, there are no studies directly comparing fixed-dose combinations as initial therapy. The Avoiding Cardiovascular events through COMbination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial compares regimens of benazepril plus amlodipine versus benazepril plus hydrochlorothiazide, force-titrated to 40/10 and 40/25mg, respectively. A total of 12,600 high-risk hypertensives have been randomised and will be followed for 3 – 5years, during which cardiovascular events will be monitored. The investigators hypothesise that the benazepril plus amlodipine regimen will decrease cardiovascular events by 15% compared with benazepril plus hydrochlorothiazide. Recruitment began in 2003, and the trial is expected to end in 2008. The ACCOMPLISH trial shares important limitations with many other recent trials that will make it difficult to apply the results in clinical practice. These include the focus on high-risk hypertensive patients, in whom significant reductions in relative risk will translate into meaningful reductions in absolute risk: in lower-risk hypertensives with a low absolute risk, similar relative risk reductions may not be of great impact on the population disease burden. In ACCOMPLISH, as in most industry-sponsored clinical trials, the main goal appears to be market-driven: doses of drugs tested are not those available for clinical practice. The question asked, whether the combination of benazepril with either diuretic or dihydropyridine calcium channel blocker is more efficacious, is not a clinically compelling one. Finally, the univariate subgroup analyses proposed are unlikely to lead to an understanding of whether either combination has specific advantages for patients encountered clinically, most of whom have multiple risk factors. Thus, it appears that ACCOMPLISH, as with many recent pharmacological trials, will not greatly impact the treatment of hypertension.     

Pirfenidone for the treatment of idiopathic pulmonary fibrosis

Introduction: Idiopathic pulmonary fibrosis (IPF) is a diffuse parenchymal lung disease with no cure. Up until recently, no treatment had been proven to alter its natural history as judged by rate of lung function decline. In 2014 however, the emergence of two novel anti-fibrotic agents, Pirfenidone and Nintedanib revolutionized the management of this condition. Both have demonstrated the ability to deliver a major reduction in the rate of chronic IPF progression.

Areas Covered: This review article focuses on Pirfenidone – a pyridone derivative initially designed as an analgesic and anti-pyretic agent. Here we describe the history of the drug from its inception through to exploratory pre-clinical in-vitro and in-vivo studies where its anti-fibrotic potential was identified, and eventually to large multicenter randomized controlled trials.

Expert Commentary: This article also summarizes some of the difficulties surrounding clinical end-point selection in IPF trials and addresses some of the challenges facing the IPF community over the coming years.     

肝纤维化中星状细胞促血管生成分子机制的研究

肝纤维化进程中存在明显的病理性血管生成与重构,阻碍了肝纤维化的逆转与恢复。血管生成及其信号调控系统已成为肝纤维化治疗的潜在靶标,血管生成抑制剂在一些实验研究中已显示出较好的抗肝纤维化疗效。肝星状细胞是肝脏中的周细胞,可以表达血管内皮生长因子、血小板衍生生长因子、瘦素、血管生成素-1等多种血管生成因子,多途径地促进病理性血管生成过程。该文对近年来肝星状细胞促进肝纤维化血管生成分子机制的研究作一综述,可以为抗肝纤维化研究提供新的视角,有助于发现新的治疗靶标。     

Somatostatin analogs for idiopathic pulmonary fibrosis therapy

Background: Idiopathic pulmonary fibrosis (IPF) is a potentially lethal disease characterized by diffuse multifocal fibrosis. SOM230 (also known as pasireotide), a somatostatin analog, is a potential antifibrotic therapy in early evaluative phase. Objective: Evaluation of data on the role of somatostatin receptors in pulmonary fibrosis and of in vivo and in vitro SOM230 antifibrotic activities. Methods/results: This study assessed somatostatin receptor expression in human normal and IPF lungs, and in animal lungs with bleomycin-induced fibrosis, as well as the effects of SOM230. The overall overexpression of somatostatin receptor subtype 2 and the anti-inflammatory/antifibrotic activities of SOM230 were demonstrated. Conclusion: These results are promising for further preclinical and clinical testing of SOM230 as an antifibrotic therapy.