肿瘤血管生成和抗血管生成治疗的研究进展

肿瘤组织中的新生血管是保证肿瘤持续生长所必需的,也是肿瘤转移的重要途径之一.针对促进肿瘤血管生成和血管生成抑制物制定新策略,采用合适手段与方法,抑制肿瘤内血管新生,消除或减少肿瘤内原有血管,可达到治愈肿瘤的目的.     

肿瘤血管生成研究进展

血管生成是肿瘤生长和转移的重要原因，如能找到有效调节血管生成的途径，则有望控制肿瘤的生长和转移。本文综述了血管生成的分子生物学机制，以及几种有前途的抗血管生成药物的基础和临床研究进展。     

肿瘤血管生成因子的研究进展

许多肿瘤的生长和转移与微血管生成密切相关,它们通过各种机制降解血管基底膜和周围细胞外基质,促进内皮细胞分裂、游走和增殖,诱导宿主毛细血管新生并长入瘤组织。现已分离、克隆、鉴定了２０ 多种肿瘤血管生成因子,对其深入研究可为肿瘤的诊断、治疗提供理论和实践依据。     

肿瘤血管生成抑制剂的研究进展

70年代初，Folkman提出肿瘤生长依赖于血管形成的概念。随之国内外大量研究证明肿瘤血管生成与肿瘤生长、侵袭和转移等特性密切相关，从而产生了肿瘤血管生成抑制疗法。因此，以肿瘤血管生成为靶点，开发肿瘤血管生成抑制剂（tumor angiogenesis inhibitor）在抗肿瘤治疗中已成为一个研究热点。目前大部分肿瘤血管抑制剂仍处于Ⅰ、期临床实验阶段，部分进入Ⅲ期临床实验，并取得较理想的疗效。本文对几类常用的肿瘤血管生成抑制剂作一介绍。     

血管生成拟态的研究进展

1971年Folkman[1]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。在深入的研究中发现,肿瘤直径达到1～2 mm后,若无新生血管生成来提供营养,则不能继续增长。因此,抑制肿瘤血管生成可望成为治疗肿瘤的新途径。     

抗血管生成疗法治疗肿瘤的研究进展

目前肿瘤的抗血管生成治疗已成为肿瘤研究的热点及肿瘤治疗的新策略。本文就肿瘤抗血管治疗的基本理论、常用抗血管生成抑制剂的种类、以及目前的应用进展作一综述。     

血管内皮生长因子与肿瘤血管生成的研究进展

肿瘤的无限制侵袭性生长及转移依赖于血管的生成。肿瘤血管生成是一个复杂的多步骤过程,且有众多生长因子的参与,其中血管内皮生长因子(Vascular endothelial growth factor,VEGF)是最重要的促血管生长因子,与肿瘤的生长、转移及预后有关,也是抗肿瘤血管生成治疗的重要靶点之一。本文旨在对VEGF与肿瘤血管生成的研究进展作一综述。     

DLL4／Notch信号传导途径调节肿瘤血管生成的研究进展

Folkman[1]于1971年提出的"肿瘤血管生成依赖学说"使人们对肿瘤生长与新生血管形成的关系有了较为深刻的认识,抗肿瘤新生血管形成成为肿瘤综合治疗的重要策略之一。其中,研究较多、也最有价值的是通过阻断血管内皮生长因子(vascular endothelial growth factor,VEGF)及其主要受体(VEGFR2)来     

整合素与肿瘤血管生成及抗血管生成作用

肿瘤血管生成不仅与肿瘤的生长和转移密切相关 ,而且在肿瘤病理分级、治疗和预后判断上具有重要的评估价值。研究表明 ,细胞粘附分子介导的细胞粘附行为异常在肿瘤的浸润和转移中有重要作用。近年 ,随着免疫和分子生物学的发展 ,肿瘤血管生成及抗血管生成逐渐成为肿瘤研究的重点和热点之一 ,细胞粘附分子与血管生成的关系也日益受到关注〔1〕。现就其中整合素家族在肿瘤血管生成及抗血管生成中的作用作一简要综述。1　整合素分子的基本结构整合素家族 (ｉｎｔｅｇｒｉｎｆａｍｉｌｙ)为细胞粘附分子家族的重要成员之一 ,是一组广泛分布于细…     

肿瘤血管生成抑制剂

人体任何组织细胞的生存、增殖均需要血管供应充足的营养物质和排除代谢产物。肿瘤特别是恶性肿瘤由于其增殖新生比正常细胞快 ,比正常细胞需求更多的营养物 ,对缺乏营养物质及氧更为敏感。因此 ,肿瘤的发生、发展和转移与血管的生成密切相关。研究证明原发瘤和转移瘤生长到0 2ｃｍ时 ,如果没有新生血管供应营养 ,肿瘤将停止生长并死亡〔1〕。肿瘤细胞也不可能通过血管而转移。断绝或减少肿瘤血管供养 ,抑制肿瘤血管的生成成了近 10年来抗肿瘤发生、发展与转移研究的热点。国内外已有报道 ,乳腺癌、结肠癌、肾细胞癌等瘤区微血管的密度与癌…     

Matrix-degrading proteases and angiogenesis during development and tumor formation

Embryonic development and tumor progression both require the exquisite coordination of programs for extracellular matrix (ECM) formation and remodeling, and those for angiogenesis and vascular development. Without a vascular supply the normal tissue or tumor is limited in size and organization. Without ECM remodeling the alteration of tissue and tumor boundaries and cellular migrations are limited. Recent insights into the molecular mechanisms regulating the extracellular environment of the growing embryonic tissue or tumors have implicated proteases, the matrix metalloproteinases (MMPs) in particular, in both the process of ECM remodeling and angiogenesis, and in a potential causal relationship between these processes. This review focuses on the roles that MMPs play in regulating three processes in which both proteolysis and vascular development are tightly coordinated: embryo implantation, bone development and tumor progression.     

Vascular endothelial growth factor and endometriotic angiogenesis

Peritoneal endometriosis is a significant debilitating gynaecological problem of widespread prevalence. It is now generally accepted that the pathogenesis of peritoneal endometriosis involves the implantation of exfoliated endometrium. Essential for its survival is the generation and maintenance of an extensive blood supply both within and surrounding the ectopic tissue. The vascular endothelial growth factor (VEGF) family of angiogenic molecules is involved in both physiological angiogenesis, and a number of pathological conditions that are characterized by excessive angiogenesis. Increasing evidence suggests that the VEGF family may also be involved with both the aetiology and maintenance of peritoneal endometriosis. Sources of this factor include the eutopic endometrium, ectopic endometriotic tissue and peritoneal fluid macrophages. Important to its aetiology is the correct peritoneal environment in which the exfoliated endometrium is seeded and implants. Established ectopic tissue is then dependent on the peritoneal environment for its survival, an environment that supports angiogenesis. Our increasing knowledge of the involvement of the VEGF family in endometriotic angiogenesis raises the possibility of novel approaches to its medical management, with particular focus on the anti-angiogenic control of the action of VEGF.     

Vascular patterning of the quail coronary system during development

Recent studies have provided insights into specific events that contribute to vasculogenesis and angiogenesis in the developing coronary vasculature. This study focused on the developmental progression of coronary vascularization beginning with tube formation and ending with the establishment of a coronary arterial tree. We used electron microscopy, histology of serial sections, and immunohistochemistry in order to provide a comprehensive view of coronary vessel formation during the embryonic and fetal periods of the quail heart, a species that has been used in a number of studies addressing myocardial vascularization. Our data reveal features of progenitor cells and blood islands, tubular formation, and the anatomical relationship of a transformed periarterial tubular network and sympathetic ganglia to the emergence and branching of the right and left coronary arteries. We have traced the pattern of coronary artery branching and documented its innervation. Finally, our data include the relationship of fibronectin, laminin, and apoptosis to coronary artery growth. Our findings bring together morphological events that occur over the embryonic and fetal periods and provide a baseline for studies into the mechanisms that regulate the various events that occur during these time periods.     

The molecular control of angiogenesis

Angiogenesis is a key event in a broad range of pathological conditions including both diseases with an enhanced and insufficient angiogenesis. Angiogenesis is often initiated with vasodilation accompanied by an increase in vascular permeability. After destabilization of the vessel wall and degradation of the surrounding extracellular matrix, extravasation of plasma proteins provides a provisional scaffold for the migration of endothelial cells. Endothelial cell proliferation and migration themselves are under tight control by a balance of angiogenesis inducers and inhibitors. A large number of angiogenic factors work together in a highly coordinated manner to induce endothelial cell outgrowth and the formation of functional vessels. On the other hand, angiostatic factors may play a critical role in the pathogenesis of ischemic diseases and contribute to the termination of physiological angiogenesis. Angiogenesis ends with the recruitment of pericytes and smooth muscle cells, which stabilize the newly formed vessel. The rapid increase in the knowledge about the molecular mechanisms of angiogenesis has led to first treatment trials in diseases with both enhanced and reduced angiogenesis. Although initial results are promising, much more work has to be done to consider anti-angiogenic or pro-angiogenic approaches as reliable therapeutic tools.     

毛囊形态学发生期的分子调控研究进展

<正>动物的毛囊(hair follicle)是皮肤表皮向真皮下陷而形成的重要附属结构,毛囊的底部可深达皮下组织内,是毛发生长起点。毛囊的生长发育能力很强,而且在动物皮肤中终生成周期性生长变化的器官。毛囊被认为是起源于神经外胚层和中胚层,并且相互作用而形成的微小器官~([1]),毛囊的形态发生起始于早期胚胎阶段,是干细胞研究及系统生物学研究的理想模型~([2])。对于动物来说,其毛发的品质及商品价值的高低主要取决于毛囊的结构和特性,因此,研究毛囊的发育生物学及其分子调控是     

c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression

c-Myc promotes cell growth and transformation by ill-defined mechanisms. c-myc(-/-) mice die by embryonic day 10.5 (E10.5) with defects in growth and in cardiac and neural development. Here we report that the lethality of c-myc(-/-) embryos is also associated with profound defects in vasculogenesis and primitive erythropoiesis. Furthermore, c-myc(-/-) embryonic stem (ES) and yolk sac cells are compromised in their differentiative and growth potential. These defects are intrinsic to c-Myc, and are in part associated with a requirement for c-Myc for the expression of vascular endothelial growth factor (VEGF), as VEGF can partially rescue these defects. However, c-Myc is also required for the proper expression of other angiogenic factors in ES and yolk sac cells, including angiopoietin-2, and the angiogenic inhibitors thrombospondin-1 and angiopoietin-1. Finally, c-myc(-/-) ES cells are dramatically impaired in their ability to form tumors in immune-compromised mice, and the small tumors that sometimes develop are poorly vascularized. Therefore, c-Myc function is also necessary for the angiogenic switch that is indispensable for the progression and metastasis of tumors. These findings support the model wherein c-Myc promotes cell growth and transformation, as well as vascular and hematopoietic development, by functioning as a master regulator of angiogenic factors.