肿瘤血管生成拟态作用及其靶向治疗药物研究现状

肿瘤的发生发展是一复杂的生物学过程,实体肿瘤的生长和转移需要新生血管形成以获取血供。目前面市的抗血管生成药物主要针对的是以内皮细胞为靶向的抗肿瘤药物。然而,在肿瘤的临床治疗中该类分子靶向抑制剂对肿瘤的作用不理想。近年发现于高侵袭性肿瘤中的血管生成拟态（vasculogenic mimicry,VM）,是一种与经典肿瘤血管生成完全不同的肿瘤微循环模式,VM的发现有助于解释以抑制肿瘤血管生成为主要作用靶点的抗肿瘤药物疗效不佳的原因。     

蛋白酶激活受体在肿瘤血管生成中的作用及其靶向抗肿瘤药物研究进展

肿瘤血管生成是肿瘤生长过程中一个重要的步骤,可以为肿瘤细胞提供氧气和营养物质,也与肿瘤细胞转移有关。目前,抗血管生成被认为是肿瘤治疗的一个重要靶点。蛋白酶激活受体（PAR）是G蛋白偶联受体家族成员之一,已被证明可以作为癌基因,在多种肿瘤细胞中高表达。研究发现,PARs可被凝血酶激活,诱导血管内皮生长因子（VEGF）表达,参与肿瘤血管生成,可作为抗肿瘤血管生成的靶点。本文主要介绍了PARs的活化机制及其在肿瘤血管生成中的作用,并对近年来靶向PARs抑制肿瘤血管生成的抗肿瘤药物的结构、药理活性的研究进展进行总结。     

血管内皮细胞生长因子及其受体——抗血管生成抗肿瘤药物的新靶点

血管生成是肿瘤发展、转移所必需的，抗血管生成是目前基于生物靶点的抗肿瘤研究热点之一。血管内皮细胞生长因子(VEGF)在肿瘤血管生成中处于核心地位，因此阻断VEGF的作用可以达到抗血管生成的目的。VEGF及其受体的结构特征和生物学特性，以及结合后产生的作用机制目前巳经比较清楚，巳有多种作用于不同环节的阻断手段在临床试验，但均有缺陷。计算机辅助药物设计可以根据生物靶分子的晶体结构设计出结合力高、专属性强的小分子抑制剂巳有成功应用。因此，选择不同的部位设计作用更强更优的小分子抑制剂是新药创制的重要方向。     

血管内皮细胞生长因子受体酪氨酸激酶抑制剂

血管生成是人体肿瘤生长和转移的必要条件，抑制肿瘤细胞介导的血管生成已成为近年来寻找新型抗肿瘤药物的一个主要研究方向，血管内皮细胞生长因子（VEGF）是体内活性最强，专属性最高的促血管生成因子，故成为寻找血管生成抑制剂的重要靶点，其中靶向VEGF受体酪氨酸激酶的抑制剂令人最为关注，本文综述VEGF及其受体酪氨酸酶抑制剂的研究进展，探讨了各类抑制剂的构效关系。     

肿瘤血管生成机制及抗血管生成药物的研究进展

目的：介绍肿瘤血管生成的机制及其抑制剂的研究进展.方法：查阅国内外相关文献进行总结和归纳.结果：肿瘤血管生成的机制目前发现的有5类：芽生式、套叠式、充塞式、内皮祖细胞的参与、马赛克式及血管生成拟态.目前有一批FDA批准上市的血管生成抑制剂（如贝伐单抗、sunitinib malate和sorafenib等）已用于肿瘤的治疗,还有更多的药物正在研究之中.结论：研究肿瘤血管生成的机制对进一步研究肿瘤血管生成抑制剂有着重要的指导作用.     

苯丙素类化合物的抗血管生成的研究概况

血管生成是肿瘤发生发展的重要因素,新生血管不仅为肿瘤提供营养和氧气,还为其恶性转移提供必要条件;抗血管生成疗法治疗肿瘤已得到广泛的研究.近年来发现许多苯丙素类化合物具有显著的抗血管生成特性,从而为抗肿瘤血管生成提供了新的药物来源.本文综述了一些得到最为广泛研究的几种苯丙素类抗血管生成化合物的研究概况,并总结归纳了其作用的分子机理.     

肿瘤血管生成抑制剂

恶性肿瘤的发展与侵袭均依赖于新生血管生成。肿瘤新生血管的生成受多种调节因子作用,这些调控因子主要有：血管内皮生长因子、血管生成素,成纤维细胞生长因子,血管抑素,内皮抑素,thrombospondin(TSP-1)等。通过抑制肿瘤新生血管的生成可以阻止肿瘤的发展和转移,甚至使肿瘤消退。抗血管生成药物为肿瘤的治疗提供了一个全新的思路,本文简单讨论了肿瘤血管生成与调节机制并着重介绍肿瘤血管生成抑制剂的研究进展。     

血管内皮生长因子受体及其小分子抑制剂的研究进展

目前抗血管生成治疗是抗肿瘤研究的热点.血管内皮生长因子(VEGF)是刺激血管生成的重要因子之一,血管内皮生长因子受体(VEGFR)在肿瘤新生血管中高表达,因此成为肿瘤靶向治疗的理想靶点.以VEGF、VEGFR为靶点的抗肿瘤药物除了常见的单克隆抗体药物阿伐斯汀外,小分子抑制剂舒尼替尼、索拉非尼等也已经广泛使用;另外,一些...     

血管生成抑制因子抗肿瘤作用的研究进展

病理性血管生成是肿瘤生长和转移的关键步骤之一,因而阻断或抑制新血管生成是抗肿瘤的有效策略[1]。近年来人们对肿瘤血管的形成机制进行了广泛研究,已证明血管的生成受多种促进和抑制因子的调节,相继有多种促血管生成分子和抗血管生成分子被分离鉴定[2]。以血管生成为靶点治疗肿瘤已成为肿瘤治疗研究的热点,有多种血管生成抑制剂已进入临床试验阶段。本文对几种很有应用前景的血管生成抑制因子的研究现状作一综述。EndostatinEndostatin即血管内皮抑素,是1997年在鼠内皮细胞瘤细胞培养液中提取并命名的一种蛋白。它由胶原ⅩⅧC末端区内18…     

中药抗肿瘤血管生成的研究进展

目的介绍抗肿瘤血管生成的中药研究进展。方法广泛查阅有关资料，综述具有抗肿瘤血管生成作用的单味中药、中药单体成分和中药复方的研究概况。结果目前已有多种中药的单体或复方制剂表现出良好的抗肿瘤血管生成，从而抑制生长与转移的作用。结论从中药中筛选抗具有肿瘤血管生成作用的活性成分或单体，将是未来抗肿瘤药物研发的重要方向之一.     

Development of angiogenesis inhibitors for cancer therapy

Abundant literature exists demonstrating that tumors are dependent on angiogenesis for both tumor growth and invasion. The extent of angiogenesis in primary tumors has been demonstrated to be associated with a negative prognosis in several tumors including non-small cell lung carcinoma, prostate cancer, and in node-negative breast cancer, where angiogenesis is an independent negative prognostic factor. These data demonstrate the significance of angiogenesis in tumor biology and indicate that it can be utilized as a target for novel therapeutic strategies. The recent expansion of knowledge into the specific pathways of tumor angiogenesis has provided reagents which can now be utilized to provide markers of efficacy of antiangiogenic agents in cancer patients. A critical part of the development of angiogenesis inhibitors for cancer therapy is the clinical trial strategy. Since these agents are primarily thought to be cytostatic, carefully designed trials must be conducted which focus on appropriate endpoints and integrate relevant biologic markers to support efficacy.     

An overview of clinical trials involving inhibitors of angiogenesis and their mechanism of action

Angiogenesis is a biologic process whereby endothelial cells divide and migrate to form new blood vessels. This process is required in physiological conditions, but is also a necessary requirement for solid tumors to grow and metastasize. Over the last several years, the growth factors that have both a positive and negative influence on tumor angiogenesis have been delineated. Interfering with tumor angiogenesis was considered a potential therapeutic strategy 25 years ago, but only recently have compounds with an ability to interfere with angiogenesis entered clinical trials. This review will discuss the first generation of angiogenesis inhibitors, their mechanism of action and data from clinical trials.     

血管生成实验模型研究进展

抗血管生成已经成为治疗肿瘤转移、糖尿病视网膜病变、风湿性关节炎等疾病的重要策略之一。血管生成模型作为一种研究工具在探讨血管形成机制、发现促进或抑制血管生成药物等研究中发挥十分积极的作用。如何寻找适合的血管生成模型是研究人员在研究中常遇到的问题。该文就主要常用模型做较全面的介绍,并对其优缺点进行评价。     

紫金砂总香豆素的超声辅助提取工艺研究

目的研究超声辅助提取紫金砂中总香豆素的最佳提取工艺。方法以总香豆素提取率为指标,考察超声提取温度、提取功率、提取时间、料液比、提取次数对紫金砂总香豆素提取的影响。选用正交试验设计法对紫金砂的超声辅助提取工艺进行优选。结果超声辅助提取紫金砂中总香豆素的最佳工艺为：65℃,超声功率90w,以1：18的料液比加入丙酮,超声提取50min,提取4次。结论通过验证实验,表明所选的工艺条件可行,在该工艺条件下每克紫金砂平均可提取总香豆素27．4mg。     

The preclinical evaluation of angiogenesis inhibitors

Angiogenesis is a fundamental process which is required for a number of physiological and pathophysiological processes. The field of angiogenesis therefore has many therapeutic implications and has progressed rapidly. Many strategies have been devised to regulate angiogenesis and several endogenous and synthetic inhibitors of angiogenesis have now been identified. These inhibitors can be used to treat a number of angiogenesis-dependent diseases and they offer a novel means of potently inhibiting tumor growth without significant toxicity or drug resistance. Recently, some of these inhibitors have entered clinical trials. In this article, I will review methods currently employed in the preclinical evaluation of angiogenesis inhibitors and I will discuss some of the implications of angiogenesis research.     

Peroxisome proliferator-activated receptor-γ ligands as investigational modulators of angiogenesis

PPAR-γ ligands constitute important insulin sensitizers that have already been approved for the treatment of human metabolic disorders. They also exert pleiotropic effects on cell proliferation and cancer and are now being explored in preclinical studies. Angiogenesis constitutes a multifaceted process that is implicated in tumor development and other benign disease states that are associated with diabetes. Recent data have further extended the crucial role of PPAR-γ ligands as potential angiogenesis modulators, in vitro and in vivo. This review summarizes the latest knowledge of the role of PPAR-γ ligands in angiogenesis that are related to both malignant and non-malignant disease states. Taking into careful consideration the data so far, PPAR-γ could be considered as a therapeutic target for diverse disease states in which excessive angiogenesis is implicated, including cancer and diabetes complications.     

成年脑血管新生与抑郁症

成年脑神经元再生障碍是抑郁症发生的重要的细胞生物学基础之一。近年研究发现,成年脑血管新生与神经元再生存在密切关系,成年脑血管新生(angiogenesis)是指原有的血管萌生出新的微血管,再形成新的血管的过程。多种血管新生因子尤其是血管内皮生长因子(vascular endothelial growth factor,VEGF)不仅具有促血管新生作用,还具有神经营养和神经保护以及促神经元再生的作用,可能参与抑郁症的发生与恢复,该文就脑血管新生与抑郁症关系的最新研究进展进行综述。     

Regulators of colon cancer angiogenesis

Folkman’s discovery that the growth and spread of tumours depend on angiogenesis has created new avenues of research designed to better understand cancer biology and facilitate the development of new therapeutic strategies. The survival and metastasis of tumours depend on a shift in the normal balance among myriad endogenous angiogenic and anti-angiogenic factors in favour of increased angiogenesis. Several growth factors that regulate angiogenesis in colon cancer have been identified, including the pro-angiogenic factors vascular endothelial growth factor (VEGF), platelet-derived endothelial cell growth factor (PD-ECGF) and the anti-angiogenic factor, thrombospondin. A thorough understanding of the roles that these factors play in the angiogenic process has led to the development of agents intended to inhibit tumour angiogenesis. However, the complexity and redundancy of the angiogenic process continue to present substantial challenges to the development of anticancer therapies.