中药抗肿瘤血管生成研究述略

血管生成是实体瘤生长、浸润和转移的一个重要因素，因此肿瘤血管生成已成为抗肿瘤治疗的新靶点。与传统的肿瘤治疗相比，抗肿瘤血管生成药物主要针对已经启动的新生血管，故具有特异性。而且血管内皮细胞暴露于血流中，药物能直接发挥作用，故有剂量小、疗效高、一般不造成骨髓抑制、胃     

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。     

血管内皮细胞生长因子及其阻断在抗肿瘤中的应用

血管新生是实体瘤生长和转移的必要条件。血管内皮细胞生长因子(VEGF)及其受体在肿瘤血管新生中起重要作用，阻断VEGF的生成已成为抗肿瘤治疗的新靶点。     

内源性血管生成抑制因子Arresten研究进展

早在1971年,Folkman就提出,肿瘤的生长与转移依赖于新生血管的生成。新生血管沟通循环系统,为肿瘤提供氧气及营养物质,并及时运走代谢产物,促使肿瘤快速生长;新生血管内皮细胞还可以分泌多种生长因子,以旁分泌方式刺激肿瘤细胞增殖;同时通过血液循环将原发癌细胞输送至远处靶器官,为癌细胞提供播散路径。肿瘤血管新生是涉及血管通透性增加、局部基底膜降解、内皮细胞迁移、毛细血管芽生、侵袭周围基质、新血管腔形成等一系列变化的一个多项过程。机体通过调节血管生成因子和抑制因子之间的平衡状态来影响内皮细胞的活动状态,调控血管生成过程。近年来,通过抑制血管生成而抗肿瘤的治疗方法引起人们的广泛关注。     

整合素αvβ3拮抗剂的研究进展

肿瘤生长初期没有新血管生成（无血管期）,其生长到一定程度时依赖新生血管的维持.肿瘤血管生成是肿瘤生长和转移的形态学基础,它不仅向肿瘤提供营养,也向宿主输出大量的肿瘤细胞导致肿瘤的生长和转移.因此对以抑制肿瘤血管生成为目的的抗肿瘤药物的研究方兴未艾,有很多具有抑制肿瘤血管生成作用的化合物如大黄素与青蒿琥酯等被发现.整合素αvβ3介导血管内皮细胞和肿瘤细胞的黏附,参与血管生成和肿瘤转移,在肿瘤生长中起重要作用.当其功能受到抑制时,血管内皮细胞出现凋亡,肿瘤生长受到抑制,甚至肿瘤消退.整合素αvβ3受体拮抗剂作为抗新生血管肿瘤药物的同时,对骨质流失、血栓、风湿性关节炎的治疗也起了重要作用.     

作用于VEGF信号通路的血管生成抑制剂

分类介绍作用于血管内皮细胞生长因子信号通路的血管生成抑制剂研究近况以及该类药物存在的缺陷。血管生长促进因子和血管抑制因子的活性及其表达水平对肿瘤的发生和发展具有关键性的作用,所以,针对于血管生成,尤其是靶向于血管内皮细胞生长因子的药物已成为近年来抗肿瘤药物研究的热点之一。     

靶向血管内皮生长因子及受体治疗肿瘤的研究进展

肿瘤的体积超过2～3mm~3时必须依赖新生血管的形成。血管生成(angiogenesis)是肿瘤生长转移的必须步骤,它是一个复杂的过程受多种促或抑血管生长因子的调控。其中血管内皮生长因子(vascular endothelial growth factor,VEGF)是已知作用最强,特异性最高的促血管生成因子。它是高度特异性的血管内皮细胞有丝分裂原,通过与血管内皮细胞特异性表达的受体Flt-1、Flk-1/KDR等结合,可显著增加血管通透性,刺激内皮细胞的增殖,直接诱导肿瘤新生血管的形成,从而为抗肿瘤提供了一种很有发展前途的治疗方法。现就抑制VEGF及其受体治疗肿瘤的研究现状作简要综述。     

血管生成抑制因子与抗癌治疗

药物耐受性是肿瘤化疗面临的主要问题之一 ,其原因是肿瘤细胞的异质性、遗传不稳定和突变率高。血管内皮细胞均质 ,遗传稳定 ,突变率较低 ,是较为理想的靶细胞。控制肿瘤内部血管生成 ,就能抑制肿瘤生长和肿瘤转移灶的形成。经过近 2 0年的努力 ,有关研究已取得了重大进展。血管生成抑制因子已显示出良好的抗肿瘤前景。1　血管生成是肿瘤转移的基础1 .1血管生成是肿瘤转移的必要途径　血管生成为肿瘤生长提供必要的营养物质和氧气 ,是肿瘤细胞进入血液的有效通道。新生血管几乎没有基底膜 ,细胞间连结复合物少 ,渗透能力强 ,1 cm3 肿瘤组织…     

EphA2与肿瘤血管生成拟态的研究进展

肿瘤血管生成是实体瘤侵袭转移的关键步骤．1971年Folkman提出了肿瘤生长依赖血管新生的假说．由此拉开了近代关于肿瘤血管生成研究的序幕。随着本世纪基因技术的飞速进展及靶向治疗的广泛应用．研究者越来越多的将抗肿瘤治疗的目光集中在抑制肿瘤新生血管生成方面．抗血管生成治疗已成为当前研究的焦点。     

血管内皮生长因子及其受体在抗肿瘤治疗应用的研究进展

肿瘤的生长依赖肿瘤新生血管的形成。血管内皮生长因子（VEGF）是一类能促进血管生成的细胞因子，能诱导细胞的有丝分裂和调节内皮细胞的通透性。VEGF及其受体介导的肿瘤血管新生在肿瘤的生长和转移中具有重要的作用。本文综述了VEGF及其受体的分类、作用机制及在抗肿瘤治疗中的应用。     

Tumor angiogenesis--a potential target in cancer chemoprevention.

Tumor angiogenesis is critically important for the growth of solid tumors as tumors remain in dormant phase for a long time in the absence of the initiation of blood vessel formation. Tumors can grow up to approximately 2mm size without requirement of blood supply as diffusion is sufficient at this level to support the removal of wastes from and supply of nutrients to tumor cells. Therefore, angiogenesis process could be an important target to suppress tumor growth and metastasis. Angiogenesis is required at almost every step of tumor progression and metastasis, and tumor vasculature has been identified as strong prognostic marker for tumor grading. Endothelial cells are the main players of angiogenesis process and could be peculiar target for antiangiogenic therapy because they are non-transformed and easily accessible to achievable concentrations of antiangiogenic agents, and also are unlikely to acquire drug resistance. Several antiangiogenic strategies have been developed to inhibit tumor growth by targeting different components of tumor angiogenesis. Chemopreventive agents have been shown to target and inhibit different aspects and components of angiogenesis process and can be used conveniently as they are mostly non-toxic natural compounds and could be part of our daily diet. However, a risk assessment for the use of antiangiogenic phytochemicals is needed as they can also disrupt normal physiologic angiogenesis such as wound healing and endometrium development processes. This review focuses on how different chemopreventive phytochemicals target various components of angiogenesis, including angiogenic signaling, which usually starts from tumor cells producing angiogenic factors and affecting endothelial cells growth, migration and capillary vessel organization for tumor angiogenesis.     

Inhibition of Tumor Growth and Metastasis by Targeting Tumor-Associated Angiogenesis with Antagonists to the Receptors of Vascular Endothelial Growth Factor

Angiogenesis, the formation of new blood vessels, is essential for both tumor growth and metastasis. Recent advances in our understanding of the molecular mechanisms underlying the angiogenesis process and its regulation have led to the discovery of a variety of pharmaceutical agents with anti-angiogenic activity. The potential application of these angiogenesis inhibitors is currently under intense clinical and pre-clinical investigation. Compelling evidence suggests that vascular endothelial growth factor (VEGF) and its receptors play critical roles in tumor-associated angiogenesis, and that they represent good targets for therapeutic intervention. This has been demonstrated in a variety of animal tumor models in which disabling the function of VEGF and its receptors was shown to inhibit both tumor growth and metastasis. We have produced a panel of antibodies directed against the VEGF receptor 2, KDR/Flk-1. These antibodies potently block VEGF/KDR/Flk-1 interaction, and inhibit VEGF-stimulated activation of the receptor and proliferation of human endothelial cells. Further, the antibodies significantly inhibited tumor-associated angiogenesis in several animal models. Antagonists of VEGF and/or its receptors may offer higher specificity towards tumors with reduced side effects, and may be less likely to elicit drug resistance compared to conventional therapy. Anti-angiogenesis therapy represents a novel strategy for the treatment of cancer and other human disorders where pathological angiogenesis is involved.     

靶向血管内皮生长因子及其受体的抗肿瘤药物研究进展

血管生成对肿瘤的生长和转移起着关键作用,血管内皮生长因子（VEGF）及其受体信号通路是调节肿瘤新生血管生成的重要途径,因此,近年来以VEGF及其受体为作用靶标的抗肿瘤血管生成治疗已经成为研究热点,目前已有多种药物上市或处于临床试验阶段。本文主要综述了VEGF及其受体在肿瘤血管生成调节机制中的作用,同时着重介绍靶向VEGF及其受体的抗肿瘤药物的新近研究进展、临床应用及存在的问题。     

Near-infrared light-activated IR780-loaded liposomes for anti-tumor angiogenesis and Photothermal therapy

Tumor angiogenesis is a key step in the process of tumor development, and antitumor angiogenesis has a profound influence on tumor growth. Herein we report a dual-function drug delivery system comprising a Near-infrared (NIR) dye and an anti-angiogenic drug within liposomes (Lip-IR780-Sunitinib) for enhanced antitumor therapy. The hydrophobic NIR dye IR780 was loaded into the liposome phospholipid bilayer, and the bilayer would be disrupted by laser irradiation so that anti-angiogenic drug sunitinib release would be activated remotely at the tumor site. The released hydrophilic sunitinib could potentially target multiple VEGF receptors on the tumor endothelial cell surface to inhibit angiogenesis. Meanwhile, IR780-loaded liposomes kill the cancer cells by photothermal therapy. Lip-IR780-Sunitinib exhibited enhanced anti-tumor and anti-angiogenic effects in vitro and in vivo. This system facilitates easy and controlled release of cargos to achieve anti-tumor angiogenesis and photothermal therapy.     

抗肿瘤新药血管内皮抑制素的研究进展

血管内皮抑制素能特异地抑制血管内皮细胞增殖和迁移,抑制新生血管形成,切断肿瘤生长所需的营养途径,从而有效抑制肿瘤的生长和转移,是目前发现的最为理想的血管形成抑制因子,为肿瘤的治疗提供了新途径。本文对血管内皮抑制素的研究进展作一浅述。     

整合素阻断剂抗肿瘤药物研究进展

整合素是存在于细胞表面的跨膜糖蛋白受体,能介导细胞间的黏附,参与血管生成和肿瘤转移,与肿瘤的发生发展密切相关。以整合素为靶点进行抗肿瘤治疗,可有效抑制肿瘤的生长和转移。本文主要从抗肿瘤生长类药物、抗肿瘤转移类药物、抗血管生成类药物等方面对近年来整合素阻断剂抗肿瘤药物研究进展进行综述,并对整合素靶向给药的剂量问题进行了讨论。     

新的抗血管生成药物阿柏西普治疗转移性结直肠癌研究进展

新生血管生成是结直肠癌发生、生长和转移的重要机制之一。阿柏西普作为血管内皮生长因子 (vascular endothelial growth factor,VEGF)的可溶性诱饵受体,作用于靶点VEGF-A、VEGF-B和胎盘生长因子(placental growth factor,PIGF)抑制肿瘤血管的生成。最近多项研究表明阿柏西普对多种实体瘤尤其转移性结直肠癌(metastatic colorectal cancer,mCRC)有明确的抗肿瘤作用。而且美国食品药品监督管理局和欧洲药物管理局已批准阿柏西普联合5-氟尿嘧啶、亚叶酸钙和伊立替康方案(5-fluorouracil,leucovorin,irinotecan,FOLFIRI)可用于二线治疗对奥沙利铂为基础的化疗方案耐药或进展的mCRC患者。该文就阿柏西普抗血管生成的作用机制和在mCRC中的临床试验作一综述。     

靶向给药在肿瘤治疗中的应用进展

目的：介绍近年来分子靶向药物治疗肿瘤的临床研究和应用。方法：收集国内外近期相关文献对靶向药物治疗肿瘤的现状及关键技术进行评价。结果及结论：分子靶向药物是利用肿瘤细胞与正常细胞之间分子细胞生物学上的差异，采用封闭受体、抑制血管生成、阻断信号传导通路等方法作用于肿瘤细胞特定的靶点，特异性地抑制肿瘤细胞生长，促使肿瘤细胞凋亡。分子靶向治疗比传统的化疗特异性强、毒副反应小，将成为今后肿瘤治疗的新趋势。现代生物技术发展迅猛，针对肿瘤细胞的靶向性治疗面临着前所未有的机遇和挑战，具有新的概念和内涵。现有方法或多或少都存在缺陷。充分利用多学科综合性发展的进步将加速新型靶向载体系统的出现。     

VEGF在肺癌中的表达及相关药物靶向治疗中的研究现状

血管内皮生长因子(VEGF)通过增加血管内皮的有丝分裂,促进血管内皮细胞迁移,重塑细胞外基质并增加血管的通透性,其特异性高,是诱导肿瘤血管生成作用较强的调节因子,与肺癌的发生、发展和转移有密切关系。生物靶向治疗药物中抑制血管内皮细胞生长因子受体(VEGFR)信号通路方面的研究较为广泛,这类药物已经被临床上用于治疗晚期非小细胞肺癌(NSCLC)。进一步研究VEGF及其受体在肺癌中的表达和在生物靶向药物治疗中的作用,为肺癌的发生、组织浸润、远处转移等机制的探索带来了更积极的意义,给肺癌患者带来了新的希望。     

Targeting tumorangiogenesis in lung cancer by suppression of VEGF and its receptor - results from clinical trials and novel experimental approaches

Tumor vascularisation, the formation of blood vessels is a central process to allow tumor growth beyond limited sizes and to facilitate metastasis formation. Angiogenesis is regulated by a balance of stimulatory and inhibitory factors. Angiogenic factors have been the focus of intense research since the prospects of new therapeutic approaches seemed enormous. Vascular endothelial growth factor (VEGF) has emerged as the most potent and most specific growth factor for endothelial cells and therefore a relevant target for novel anticancer therapy. A wide range of agents have been designed for their ability to interfere the VEGF signalling pathway. In addition, several drugs are currently in advanced clinical development. This review describes the current experimental strategies to inhibit VEGF and will also summarize and discuss the results of recent clinical trials involving anti-VEGF compounds either as standalone therapy or in combination with chemotherapy in lung cancer.