CXC趋化因子与肿瘤血管新生

趋化因子在免疫调节、血管新生以及介导肿瘤的器官特异性转移中发挥重要作用。其中CXC趋化因子超家族由于N-端谷氨酸-亮氨酸-精氨酸基序（Glu—Leu-Arg,ELR motif）的有无使其在血管新生过程中具有了促进或者抑制血管新生的不同作用：含有ELR（ELR^＋）的CXC趋化因子经血管内皮组织上CXCR2介导血管新生促进作用;而不含有ELR（ELR^-）的CXC趋化因子通过血管内皮组织上CXCR3介导血管新生抑制作用。     

肿瘤血管新生的数值模拟

利用Overture开发肿瘤血管新生模型的计算程序,使用有限差分法模拟肿瘤血管新生过程中,血管内皮细胞在细胞间基质中的增生和迁徙,阐明了血管内皮生长因子和血管新生因子的调节机制.针对三种调节因子的不同组合下的模型进行数值模拟,对比说明三种因子在肿瘤血管新生中的不同作用.模型计算结果与病理学现象实验一致.     

肿瘤干细胞与血管新生的研究进展

肿瘤生长及转移依赖于新生血管的形成,大量研究认为肿瘤干细胞与血管新生之间存在密切联系,肿瘤干细胞可能转分化为内皮细胞参与新生血管生成,并通过分泌促血管生长因子、基质衍生因子和低氧诱导因子参与对血管新生的调控。     

新生血管靶向肽NGR与肿瘤靶向治疗

NGR(Asn-Gly-Arg)是通过噬菌体展示技术筛选出来的能够和肿瘤新生血管特异结合的三肽模体,可以通过内皮细胞上的氨肽酶N(aminopeptidase N,亦称CD13)与新生血管发生特异性的结合。NGR多肽可以将多种药物分子和病毒载体靶向运输到肿瘤或者进行血管再生的组织中。NGR模体上的天冬酰胺脱酰胺后生成异天冬氨酸-甘氨酸-精氨酸异构体(isoDGR)。isoDGR是整联蛋白αvβ3的配体,可以作为一种新的肿瘤新生血管靶向肽用于肿瘤靶向治疗的研究。本文主要对NGR模体的结构和功能以及其在肿瘤靶向治疗中的应用作一综述。     

具新生血管抑制及血管阻断双重作用的肿瘤血管靶向药物研究进展

以血管新生抑制剂和血管阻断剂为代表的肿瘤血管靶向药物作为一种新的抗肿瘤疗法,其研究与开发已取得显著进展,尤其是二者联用已在临床实践中获得更好疗效。因而,近年来具有新生血管抑制和血管阻断双重作用的肿瘤血管靶向药物研究备受关注。这种具双重作用的肿瘤血管靶向药物因同时保持了血管新生抑制剂和血管阻断剂的各自作用特点,在临床肿瘤治疗上更具优势,不仅能一药多靶,增强抗肿瘤疗效,同时还可降低用药剂量,减少毒副作用,提高用药耐受性,故临床应用前景广阔。综述新生血管抑制剂和血管阻断剂的作用机制及特点,介绍具代表性的兼有新生血管抑制和血管阻断双重作用的肿瘤血管靶向药物研究进展。     

靶向肿瘤新生血管纳米粒的构建和质量控制

目的：制备F56多肽修饰的长春新碱纳米粒（F56-VCR-NP）,并建立其质量控制方法。方法：乳化－溶剂挥发法优化制备F56．VCR-NP：HPLC法测定其载药量、包封率,透射电镜下观察其形态,激光粒度分析仪测定其粒径和Zeta电位,CBQCA试剂盒测定纳米粒表面多肽密度,XPS进行表面元素分析。结果：优化制备的F56－VCR-NP粒径约为153nm,Zeta电位为－20．8mv,包封率为21．4％,载药量为1．9％,多肽连接效率为26．3％。结论：以聚乙二醇－聚乳酸（PEG-PLA）为原料,长春新碱为模型药物,成功制备出纳米粒子,并建立起有效的质量控制方法,对该实验样品进行了表征。结果表明此类纳米粒子尺寸均匀,表面多价连接F56多肽,载药量和包封率稳定可控,工艺成熟。     

肿瘤转移中的淋巴管新生

肿瘤转移是肿瘤致死的重要原因,临床发现,肿瘤最初的生长主要通过诱导血管新生(angiogenesis)来提供所需的营养,但是肿瘤转移的主要途径并不是通过新生血管,而是通过肿瘤诱导的新生淋巴管进行转移.淋巴管新生(1ymphangiogenesis)是在原来淋巴管的基础上长出新的毛细淋巴管的过程,毛细淋巴管仅由一层内皮细胞组成,几乎不被周细胞或平滑肌细胞包被,它是肿瘤细胞转移和扩散的重要途径.因此,肿瘤细胞通过新生淋巴管转移至淋巴结可被视为肿瘤转移的预后指标,抑制肿瘤的淋巴管新生被认为是肿瘤诊断和决定医治的重要治疗方法.但是由于缺乏淋巴特异性标记和对淋巴管新生知识的匮乏,淋巴管新生并没有像血管新生那样得到关注.近年来,淋巴管新生信号途径的阐明,淋巴内皮细胞(1ymphatic endothelial cell,LEC)分子标记物如Prox-l、LYVE-1和podoplanin等的发现和淋巴内皮细胞的成功分离和培养,使得淋巴管新生方面的研究更深入.     

血管内皮生长因子家族及其受体与肿瘤血管生成研究进展

血管内皮生长因子(vascular endothelial growth factor,VEGF),又名血管通透性因子(vascular permeability factor,VPF)是重要的血管生成正性调节因子,是目前抗癌治疗的研究靶点之一。现已发现的VEGF家族成员包括VEGF—A、VEGF—B、VEGF—C、VEGF—D、VEGF—E和胎盘生长因子(placenta growth factor,PLGF)。VEGF的受体有VEGFR—1(fit—1)、VEGFR-2(flk-1／KDR)、VEGFR-3(fit-4)、neuropilin(NPR1／NPR2)。该家族的成员可以选择性地增强血管和／或淋巴管内皮细胞的有丝分裂,刺激内皮细胞增殖并促进血管生成,提高血管特别是微小血管的通透性,使血浆大分子外渗沉积在血管外的基质中,促进新生毛细血管网的建立,为肿瘤细胞的生长提供营养等。作者对VEGF家族成员及其受体的理化特征、VEGF与肿瘤的关系、VEGF抑制剂的研制作一综述。     

血管内皮生长因子和抗肿瘤血管新生药物研究进展

肿瘤的生长与迁移离不开新血管的形成,这使得抗血管新生成为肿瘤治疗的重要途径之一。血管内皮生长因子（VEGF）是针对内皮细胞作用最强、特异性最高的血管新生促进因子,因而VEGF是抗肿瘤治疗的重要靶点。我们简要介绍了VEGF的一些生物学特点及肿瘤血管新生,着重介绍了一些抗血管新生药物的最新研究成果及其临床应用。     

Optical imaging and tumor angiogenesis

Tumor angiogenesis is essential for tumor growth and progression. Therefore, targeting tumor blood vessels is a promising approach for cancer therapy. Angiogenesis, the formation of blood vessels, is a multistep process, and strongly influenced by the microenvironment. There are no in vitro assays that can resemble this dynamic process in vivo. For this reason, animal models and imaging technologies are critical for studying tumor angiogenesis, identifying therapeutic targets as well as validating the targets. Non-invasive molecular imaging in animal models presents an unprecedented opportunity and ability for us to perform repetitive observations and analysis of the biological processes underlying tumor angiogenesis and tumor progression in living animals in real time. As we gain a better understanding of the fundamental molecular nature of cancer, these techniques will be an important adjunct in translating the knowledge into clinical practice. This important information may elucidate how the tumor blood vessels behave and respond to certain treatments and therapies.     

糖基磷脂酰肌醇锚定蛋白质与肿瘤血管生成的关系

肿瘤血管生成是一个非常复杂的过程,涉及到多种因子的调节。目前,已发现多种糖基磷脂酰肌醇锚定蛋白质与肿瘤血管生成密切相关。尿激酶型纤溶酶原激活剂受体(urokinase plasminogen activator receptor,uPAR/CD87)、CD55、基质金属蛋白酶、T-钙黏着蛋白、RECK、Eph家族受体作用蛋白A(Eph family receptor interacting protein A,ephrin A)等均能调节肿瘤血管生成过程。本文对糖基磷脂酰肌醇锚定的调节因子如何影响肿瘤血管生成,以及它们作为肿瘤治疗的主要靶标研究进行综述,为肿瘤治疗的抗血管生成新靶标的设计提供信息。     

Immunotherapy of tumor by targeting angiogenesis

Tumor growth and metastasis are angiogenesis-dependent. Anti-angiogenic therapy represents a new strategy for the development of anti-cancer therapies. In recent years, there has been made great progress in anti-angiogenic therapy. As far as the passive immunotherapy is concerned, a recombinant humanized antibody to vascular endothelial growth factor (VEGF)-Avastin has been approved by FDA as the first angiogenesis inhibitor to treat colorectal cancer. For active specific immunotherapy, various strategies for cancer vaccines, including whole endothelial cell vaccines, dendritic cell vaccines, DNA vaccines, and peptides or protein vaccines, have been developed to break immune tolerance against important molecules associated with tumor angiogenesis and induce angiogenesis-specific immune responses. This article reviews the angiogenesis-targeted immunotherapy of tumor from the above two aspects.     

Immunotherapy of tumor by targeting angiogenesis

As early as 1971, Folkman proposed that thegrowth of and persistence of solid tumors and theirmetastasis depended on an adequate blood supply and,therefore, an anti-angiogenic strategy might be effec-tive as an anticancer therapy. As a strategy for cancertherapy, anti-angiogenic therapy attempts to stop newvessels from forming around a tumor and break up theexisting network of abnormal capillaries that feed thecancerous mass[1,2]. Anti-angiogenic therapy take someadvantages over the convention…     

微核糖核酸在肿瘤血管生成中的调节作用

微核糖核酸（microRNAs,miRNAs）是广泛存在于真核生物中的一类短小的、不编码蛋白质的RNA家族,由18-25个核苷酸组成的单链RNA。研究表明microRNAs对肿瘤的发生发展具有重要的调节作用。肿瘤血管生成是实体瘤侵袭转移的关键步骤,抗肿瘤血管生成的治疗已成为当前研究的焦点,已有研究表明,microRNAs参与肿瘤血管生成的调节作用,通过对肿瘤血管生成相关因子的调控,影响肿瘤生成。     

VEGF与肿瘤血管生成及其在抗肿瘤药物开发中的应用

肿瘤血管生成在肿瘤的形成和转移过程中起到很重要的作用,众多的血管生成因子和抑制因子在肿瘤血管生成中起到调控作用,而血管生成因子（VEGF）是其中很重要的一类,通过研究其在肿瘤血管形成过程的调节机制,找到了一条有效的预防和治疗肿瘤的新途径。本文就肿瘤血管生成、VEGF家族的特性、VEGF在抗肿瘤药物开发中的应用做一综述。     

The involvement of endothelial progenitor cells in tumor angiogenesis

Endothelial progenitor cells (EPCs) have been isolated from peripheral blood CD34, VEGFR-2, or AC 133 (CD133) antigen-positive cells, which may home to site of neovascularization and differentiate into endothelial cells in situ. Endothelial cells contribute to tumor angiogenesis, and can originate from sprouting or co-option of neighbouring pre-existing vessels. Emerging evidence indicate that bone marrow-derived circulating EPCs can contribute to tumor angiogenesis and growth of certain tumors. This review article will summarize the literature data concerning this new role played by EPCs in tumor angiogenesis.     

Perlecan and tumor angiogenesis.

Perlecan is a major heparan sulfate proteoglycan (HSPG) of basement membranes (BMs) and connective tissues. The core protein of perlecan is divided into five domains based on sequence homology to other known proteins. Commonly, the N-terminal domain I of mammalian perlecan is substituted with three HS chains that can bind a number of matrix molecules, cytokines, and growth factors. Perlecan is essential for metazoan life, as shown by genetic manipulations of nematodes, insects, and mice. There are also known human mutations that can be lethal. In vertebrates, new functions of perlecan emerged with the acquisition of a closed vascular system and skeletal connective tissues. Many of perlecan's functions may be related to the binding and presentation of growth factors to high-affinity tyrosine kinase (TK) receptors. Data are accumulating, as discussed here, that similar growth factor-mediated processes may have unwanted promoting effects on tumor cell proliferation and tumor angiogenesis. Understanding of these attributes at the molecular level may offer opportunities for therapeutic intervention.     

New molecular mediators in tumor angiogenesis

Angiogenesis is essential for tumor growth and progression. It has been demonstrated that tumor growth beyond a size 1 to 2 mm³ requires the induction of new vessels. Angiogenesis is regulated by several endogenous stimulators and inhibitors of endothelial cell migration, proliferation and tube formation. Under physiological conditions these mediators of endothelial cell growth are in balance and vessel growth is limited. In fact, within the angiogenic balance endothelial cell turnover is sufficient to maintain a functional vascular wall but does not allow vessel growth. Tumor growth an progression has successfully been correlated to the serum concentration of angiogenic mediators. Furthermore, the vascular density of tumor tissues could be correlated to the clinical course of the disease in several tumor entities. Within the last years several new mediators of endothelial cell growth have been isolated e.g. angiopoietin 1, angiopoietin 2, midkine, pleiotropin, leptin and maspin. In this review we discuss the mechanisms leading to tumor angiogenesis and describe some of the newer mediators of endothelial cell stimulation and inhibition.     

肿瘤血管生成抑制因子在实体瘤治疗中的应用

肿瘤的治疗是近年来广大科研及医务工作者共同关注的问题。本文通过对血管生成与肿瘤生长的关系、血管生成因子和血管生成抑制因子功能的阐述,说明了血管生成抑制因子在肿瘤发生过程中的可能作用,从而为实体瘤的抗血管生成疗法提供了理论依据。