促血管生成素与肿瘤性血管生成的关系

促血管生成素 (Ang)家族有 4个成员 ,其中Ang1和Ang2目前研究比较多 ,被认为与血管形成有关。体内、体外研究表明 ,Ang参与生理性和病理性血管生成。Ang家族与VEGF等其它促血管生成因子相互作用 ,共同促进肿瘤性血管生成。     

Angiostatin及其结构类似物在血管生成中的作用

Angiostatin及其结构类似物是一大类重要的内源性血管生成抑制因子 ,在机体生理、病理性血管生成的调节中起重要作用。对其结构及作用机制的深入研究将有助于新的具有临床应用价值的抗血管生成药物的研制     

血管生成素与肿瘤新生血管生成

血管生成素Angiopoietin是特异性作用于血管内皮细胞的生长因子,主要由Angiopoietin-1和Angiopoietin-2组成.Tie-2是其共同受体.Angiopoietin-1能保持血管内膜的稳定性,与VEGF协同作用,促使血管成熟.Angiopoietin-2能拮抗Angiopoietin-1的作用,破坏血管的稳态.在肿瘤血管生成过程中,Angiopoietin-2表达于肿瘤侵袭的最前沿,是血管产生的早期信号.阻断Angiopoietin/Tie-2通路可能拮抗肿瘤的血管生成.     

血管生成素及其受体与肿瘤的血管生成

血管生成素 (Ang)家族是唯一含受体激动剂及抑制剂的促血管生成因子 ,编码四种结构相似的蛋白质 ,包括Ang 1,Ang 2 ,Ang 3和Ang 4 ,均能与内皮细胞上的酪氨酸激酶受体Tie 2结合 ,参与生理性及病理性的血管生成。Ang 1激活Tie 2 ,促进血管生成 ,维持血管稳定 ;Ang 2的作用呈VEGF依赖性 ,VEGF存在时 ,可促进血管出芽 ,VEGF缺乏时 ,则促进血管退化。Ang家族在不同的肿瘤中表达水平及分布形式不一。应用sTie 2或以Ang家族为靶标可抑制肿瘤性血管生成 ,对肿瘤的治疗有潜在的应用前景。     

血管形成和抗血管形成在医学中的应用

肿瘤的生长与肿瘤血管形成密切相关,抑制肿瘤血管生成就能抑制肿瘤的生长、浸润和转移,抗肿瘤血管形成治疗近年来备受关注,导致了一种新的肿瘤治疗方法和一类新的抗肿瘤药物的出现.在闭塞性血管疾病中血管形成治疗也开始应用于临床.     

促血管生成素及其受体TEK在血管形成中的调节作用

促血管生成素（angiopoietins，ANGPT）及其受体TEK是新发现在机体的生理、病理性血管形成中发挥重要调节作用的信息途径。生理情况下，ANGPT1激活TEK受体，促进血管生成、维持血管完整稳定；ANGVF2则竞争性拮抗ANGPT1的作用，当血管内皮生长因子存在时，可促进血管重建，血管内皮生长因子缺乏时，则促进血管退化。肿瘤发生时，ANGPT及TEK受体在肿瘤组织中表达明显增高，特别是ANGPT2特异表达于肿瘤新生血管区，参与肿瘤血管新生的起始及延续过程。阻断ANGPT及TEK信号传导途径可抑制肿瘤生长，有望为肿瘤的临床治疗提供一种新途径。     

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…     

胶质瘤血管新生及其调控机制

体内外研究表明实体性肿瘤的生长是依赖血管的,其直径一旦超过2 mm,若没有新生的血管供血则肿瘤的生长就会停止。胶质瘤是人体内血管化程度最高恶性的肿瘤之一。胶质瘤的血管发生与其他实体性肿瘤血管发生一样,由血管形成及血管新生两种方式构成：前者由内皮祖细胞或者血管母细胞形成新的血管;而后者是由组织中既存的成熟血管的内皮细胞发生增殖和游走形成小血管。血管新生是肿瘤血管生成的主要形式,胶质瘤血管新生的机制研究以及抑制其血管生成是胶质瘤治疗的一个新途径,成为近年来的研究热点,本文就胶质瘤血管新生及其调控机制作一综述。     

血管生成及靶向治疗

血管是胚胎发育第一器官并形成人体最大网络系统。正常血管生成受到各种细胞因子的严格控制。异常的血管生成导致各种疾病,例如肿瘤、糖尿病、免疫病、先兆子痫、肢体缺血等。因此,血管生成已成为治疗这些疾病的药物靶点。2004年,第一个抗血管生成药物用于结肠癌的治疗,标志着抗血管生成疗法的成功。然而,随着血管生成药物的临床应用,新的问题也逐渐显露出来。这不仅给我们提出了新的挑战,而且展现出新的希望。     

血管生成素2的研究进展

血管生成素(angiopoietin,Ang)是近年来发现的与血管新生密切相关的一个新家族,包括Ang-1、Ang-2、Ang-3、Ang-4,参与胚胎血管的发生及成年机体生理、病理性血管形成,尤其Ang-2,在肿瘤组织中的表达明显高于周围正常组织。     

Role of mesenchymal cells in the neovascularization of the rabbit phallus

The neovascularization of the rabbit phallus at ages between prenatal days 15 and 21 was investigated by light- and electron microscopy, computer-aided light microscopic reconstruction, and immunocytochemistry. The phalli are embedded by an abundance of mesenchymal cells, which are in contact with the neighboring ones or with the endothelial lining of growing capillaires. They often form solid cell cords that eventually make contact with the growing capillaries. The computer-aided reconstruction of the serial light micrographs reveals that these cell cords are involved in connecting the adjacent capillaries. The incorporation of such mesenchymal cell projections into the endothelial lining, occasionally conjugated with simple attachement devices, is frequently observed by transmission and scanning electron microscopy. The contact areas between the mesenchymal and endothelial cells show immunoreactions of fibronectin. These results indicate the successive transformation of mesenchymal cells to endothelial cells of the growing capillaries. As endothelial cells of the growing capillaries show mitotic proliferation, such vasoformative mesenchymal cells seem to be involved in the acceleration of the neocapillarization of the rabbit phallus. Fibronectin actively produced in the mesenchymal cells may participate in their migration and the mechanical linkage with the endothelial cells. © 1994 Wiley-Liss, Inc.     

Expression of the angiopoietins and their receptor Tie2 in human renal clear cell carcinomas; regulation by the von Hippel-Lindau gene and hypoxia

Angiogenesis is essential for tumour growth and metastasis, and is co-ordinated by several classes of angiogenic factors. To determine the significance and regulation of the angiopoietin (Ang) pathway in highly vascular human renal cell carcinomas (RCCs), this study has investigated the expression of the Ang-1, Ang-2, Ang-4, and Tie2 genes in a series of normal (n = 26) and neoplastic (n = 45; clear cell n = 35, papillary n = 10) human kidney tissues, examined the pattern of Ang-2 and Tie2 protein expression, and correlated expression with clinicopathological variables. The effect of the von Hippel-Lindau (VHL) gene and hypoxia in the renal cell lines RCC786-0 and RCC4 has also been investigated. Ang-1, Ang-2 and Tie2, but not Ang-4 mRNA, were detected in normal and tumour samples. A significant increase in Ang-2 (p < 0.001) and a decrease in Tie2 receptor mRNA (p = 0.001) were observed, but no significant difference was observed in Ang-1 mRNA abundance between normal kidney and RCC (p = 0.37). Immunohistochemistry for Ang-2 showed strong expression in vascular endothelium and weak expression in tumour cells, whereas Tie2 was expressed exclusively on endothelium. Tie2 gene expression was positively correlated with Ang-2 expression in cancers (p = 0.001) and showed a borderline significant association with Ang-1 (p = 0.06), but there was no significant relationship between Ang-1 and Ang-2 (p = 0.69). No significant relationships were observed in clear cell carcinomas between Ang-1, Ang-2 and Tie2 mRNA abundance and patient sex, patient age, or tumour size (p > 0.05). However, there was significantly greater Ang-1 (p = 0.02), Ang-2 (p = 0.03), and Tie2 (p = 0.04) mRNA abundance in clear cell than in chromophil RCCs. Ang-2 gene expression was down-regulated by hypoxia in VHL wild-type RCC786-0 and RCC4 transfectants (p = 0.0002 and p = 0.04, respectively), mirroring the low expression in human tumour cells. These data suggest that it is endothelial induction of Ang-2 in tumours that regulates vessel stability and supports targeting Tie2 as an effective novel anti-angiogenic therapy in clear cell RCCs.     

Not just angiogenesis--wider roles for the angiopoietins

Since the discovery of the angiopoietins, much interest has been focused on their biological actions and their potential use as therapeutic targets. It is generally accepted that the angiopoietins play an important role in angiogenesis and hence are described as angiogenic factors. However, it is becoming increasingly clear that this is not their only role and it is likely that the angiopoietins have important roles in a wider range of biological and pathological functions.     

Stimulation of angiogenesis and survival of endothelial cells by human monoclonal Tie2 receptor antibody

Angiopoietin-1 (Ang1) and its endothelium-specific receptor, tyrosine kinase with Ig and epidermal growth factor homology domain 2 (Tie2), play critical roles in vascular development. Although the Ang1/Tie2 system has been considered a promising target for therapeutic neovascularization, several imitations of large-scale production have hampered the development of recombinant Ang1 for therapeutics. In this study, we produced a fully human agonistic antibody against Tie2, designated 1–4h, and tested the applicability of 1–4h as an alternative to native Ang1 in therapeutic angiogenesis. 1–4h significantly enhanced the phosphorylation of Tie2 in a dose- and time-dependent manner in human Tie2-expressing HEK293 cells and human umbilical vein endothelial cells. Moreover, 1–4h induced the activation of Tie2-mediated intracellular signaling such as AKT, eNOS, MAPK, and Focal Adhesion Kinase p125^FAK. In addition, 1–4h increased the chemotactic motility and capillary-like tube formation of endothelial cells in vitro and enhanced the survival of serum-deprived endothelial cells. Taken together, our data clearly suggest that a human Tie2 agonistic antibody is a potentially useful therapeutic approach for the treatment of several ischemic diseases including delayed-wound healing and ischemic heart and limb diseases.     

Immunohistochemical detection of the angiopoietins during porcine metanephric kidney development

Angiopoietins are growth factors involved in vascular development. They also play an important role in the development of the kidney vasculature. The localization of these growth factors was immunohistochemically investigated in developing porcine metanephric kidneys. Angiopoietin 1 was predominantly present in the maturing glomeruli, while angiopoietin 2 was observed in the early developing glomeruli as well as in maturing glomeruli. Furthermore, angiopoietin 2 was observed in the muscle layer of renal arteries, in the convoluted tubules and in the loops of Henle. In contrast to the situation in the mouse in which angiopoietin 2 has been reported to be mainly expressed in mesangial cells near the glomerular hilus, expression of angiopoietin 2 in the porcine metanephric kidney was observed in the podocytes of early developing glomeruli, but not in the cells near the glomerular hilus. The results of this study support the hypothesis that the angiopoietins play an important role during mammalian metanephric development and during glomerulogenesis in particular, but indicate that species specific characteristics must be taken into account when evaluating their involvement in glomerulogenesis.     

电刺激效应在血管新生中的作用

人体生命活动的不断延续,往往伴随着生物电现象的产生,一旦这种电生理环境发生改变,机体易于陷入疾病状态。那么基于这种电生理环境的改变以及电刺激技术的发展,借助电刺激技术改变疾病状态。从而修复机体结构和功能的治疗手段得到大量研究者的证实。血管新生是一个多因素参与、多步骤演变的过程。多种病变情况下如创伤愈合、组织再生修复和肿瘤生长、转移均牵涉到血管的新生,同时也伴随着生物电现象的变化。就近年来电刺激技术作用于血管新生的研究进展作一综述。     

电磁场与组织工程组织血管形成

组织工程的血管化问题是制约组织工程产品的关键问题之一.为了解决这一问题,一些研究者使用电磁技术作用于内皮细胞或动物体观察血管形成情况.就电磁场对组织工程组织血管形成的影响作一综述.     

骨髓源性血管内皮前体细胞与出生后生理性和病理性血管形成

Endothelial progenitor cells （EPCs） exist in bone marrow, umbilical cord blood and peripheral blood of adult mammals, including humans. Furthermore, the discovery of EPCs has led to the notion of adult vasculogenesis, in which bone marrow (BM)-derived EPCs home to and incorporate into sites of new blood vessel formation, where they differentiate into endothelial cells, which is consistent with postnatal vasculogenesis. It has become apparent that circulating BM-derived EPCs are involved in promoting physiologic andpathologic neovascularization, such as wound healing and tumor growth. They are of great clinical importance in pro-or anti-angiogenic therapies.     

乳腺癌间质新生血管周细胞的形态学特点及其意义

研究乳腺癌间质新生血管周细胞形态学特点、特异性标记及其与内皮的关系,并定量分析周细胞与血管密度的关系。方法应用超微结构、免疫组织化学ＬＳＡＢ法及形态定量,对８９例乳腺癌及４例新鲜内 组织新生血管的周细胞进行系统形态学观察。结果内皮细胞第八因子相关抗原表达阳必 质内含有特征的Ⅷ因子小体（Ｗｅｉｂｅｌ－ｐａｌａｄｅ ｂｏｄｙ）。周细胞α－平滑肌肌动蛋白的表达阳性,胞质内含有丰富的肌丝,与内皮细胞间可见