妇科肿瘤的血管形成和抗血管形成治疗研究进展

肿瘤的生长和转移需要新生血管提供血液,抗肿瘤血管形成是一种新的抗肿瘤策略。本文对妇科肿瘤领域中有关肿瘤微血管密度的检测及其预后价值、肿瘤组织血管形成活性分子的检测、血清血管形成分子的检测、抗肿瘤血管形成治疗尝试及其在妇科肿瘤治疗中的地位等问题进行了综述。     

肿瘤血管形成抑制物的研究

血管形成对于原发瘤的持续生长和继发瘤的形成、生长起到关键的作用。小于１～２ｍ的肿瘤主要通过弥散获取营养,若继续生长则需依赖新生毛细血管的形成来提供充足的血液,否则肿瘤组织将发生退化［１］。早在１９７１年,Ｆｏｌｋｍａｎ就首先提出了控制肿瘤生长的新途径—抗血管     

肿瘤淋巴管形成与肿瘤转移关系的研究进展

恶性肿瘤是严重危害人类健康的常见疾病 ,造成恶性肿瘤治疗困难的主要原因之一是恶性肿瘤常发生远处部位的转移。如果肿瘤只局限在原发部位 ,则通过手术等方法可使患者治愈 ,转移是肿瘤患者死亡的主要原因。肿瘤发生播散和转移的途径主要有 :(1)局部浸润 ,体腔、体表种植 ;(2 )通过血管的血行转移 ;(3)通过淋巴管的淋巴转移等。其中通过淋巴管常常是某些肿瘤初始转移阶段的最主要途径 ,肿瘤细胞进入引流淋巴结 ,继而再进入血流 ,造成更广泛的远处转移 ,威胁患者的生命。在过去的 10余年中 ,肿瘤新生血管的研究成为肿瘤研究的一个热点。自 19…     

肿瘤血管形成的生物学特性和临床意义

肿瘤血管形成的生物学特性和临床意义＊１陈莉综述２宗永生审校＊美国中华医学会（ＣＭＢ）资助课题（Ｎｏ．１３７２９）作者单位：１南通医学院病理解剖教研室，南通２２６００１２中山医科大学病理解剖教研室，广州５１００８９肿瘤是典型的血管依赖性病变〔１〕，血管...     

肿瘤血管拟态形成机制研究进展

<正>血管生成拟态(vasculogenic Mimicry,VM)是近年来提出的一个肿瘤微循环的全新概念。与经典的血管生成途径完全不同,VM是高侵袭性肿瘤为了满足自身的血液供应,通过自身表型和细胞外基质重塑而围成的一种类血管样的管道,是不依赖血管内皮细胞的一种肿瘤微循环模式,VM的发现解释了以抑制肿瘤血管生成为主要作用靶点的抗肿     

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…     

以抑制肿瘤新生血管为靶点的抗肿瘤药物研究进展

恶性肿瘤的生长和转移与肿瘤区域的血管密切相关,肿瘤区域的新生毛细血管是肿瘤赖以生长和生存的物质基础,肿瘤细胞需要新生血管为迅速生长的肿瘤提供营养物质和排出废物。早在七十年代初就有人提出把抑制肿瘤血管形成作为肿瘤治疗的一种途径,以后这种以肿瘤血管为靶标的治疗策     

肿瘤间质肌纤维母细胞的促血管形成作用

肌纤维母细胞是肿瘤性间质最主要成员之一，在肿瘤性血管形成中起重要作用。间质肌纤维母细胞通过旁分泌或自分泌的形式参与肿瘤间质重构和促血管形成因子的产生，直接或间接促使内皮细胞和血管周细胞的分化、增殖以及募集，促进肿瘤性血管形成。     

一氧化氮与肿瘤血管形成关系的研究进展

一氧化氮 (NO)是一种信使分子和细胞毒性因子 ,对于肿瘤细胞生长具有双重作用 ,本文介绍NO作为多种血管生长因子 (VEGF、bFGF等 )的信号转导物 ,通过介导肿瘤血管形成发挥促进肿瘤生长、发展、转移的作用。     

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。     

Altered angiogenesis in the tumor microenvironment

Tumor blood vessels play an important role in tumor progression and metastasis. Thus, targeting the tumor blood vessels is an important strategy in cancer therapy. Tumor blood vessels generally arise from pre-existing vessels and have been thought to be genetically normal. However, they have been shown to differ from their normal counterparts, e.g. with regard to the morphological changes. We isolated tumor endothelial cells (TEC) from mouse tumor xenografts and showed that they were abnormal. TEC up-regulate many genes, proliferate more rapidly and migrate more than normal endothelial cells (NEC). Furthermore, the TEC in our study were cytogenetically abnormal. We concluded that TEC can acquire cytogenetic abnormalities while in the tumor microenvironment. In order to develop ideal antiangiogenic therapies, understanding the crosstalk between blood vessels and the tumor microenvironment is important. This review considers the current studies on TEC abnormalities and discusses the possible mechanism by which the tumor microenvironment produces abnormal TEC.     

蛋白多糖在肿瘤血管生成中的作用

血管生成是肿瘤进展中的一个重要环节。蛋白多糖(proteoglycans,PGs)由核心蛋白和不同的糖胺聚糖(glycosaminoglycans,GAGs)侧链构成,属于细胞外基质(extracellular matrix,ECM)的非胶原重要成分。研究显示PGs与肿瘤的发生发展密切相关,可参与肿瘤血管生成过程。由于其侧链的不同,功能上也会出现差异,表现出促进或抑制肿瘤血管生成的作用。本文就PGs在肿瘤血管生成中的作用研究现状作一综述。     

Progress of EGFL6 in angiogenesis and tumor development

The epidermal growth factor (EGF) superfamily includes the protein 6 with an epidermal growth factor-like protein (EGFL6). EGFL6 has a signal peptide domain with an amino terminus and a MAM domain with a carboxy terminus. There are four whole EGF-like repeat regions and one partial EGF-like repeat region. Three of these regions include calcium-binding structures and an arg-gly-asp (RGD) integrin interaction motif. The epidermal growth factor-like (EGFL) and EGF domains have identical amino acid residues. Cell division, differentiation, mortality, cell adhesion, and migration are all affected by EGFL6. EGFL proteins are involved in a broad range of biological activities, making it important in tumor development and angiogenesis. We highlighted the latest development of EGFL6 research on tumor proliferation, invasion, and migration in this review.     

Robo家族蛋白在神经元轴突发育和肿瘤血管生成中的作用

Robo家族（Roundabout family）是与发育有关的保守跨膜蛋白家族,主要表达于神经系统并在神经元轴突发育中发挥重要作用。近期,人们研究发现Robo家族的一个新成员Robo4(又称magic roundabout,MRB)特异表达于血管生成活跃的内皮细胞表面,并参与调控内皮细胞迁移。成年人正常组织中不表达MRB,而肿瘤组织相对特异性高表达,MRB有望成为抑制血管生成治疗肿瘤的新靶点。     

骨髓来源免疫细胞对肿瘤血管生成的调节及临床应用研究进展

 近年来研究发现髓系细胞在肿瘤血管生成中发挥关键的调控作用。髓系细胞可以通过多种途径促进血管生成,包括分泌VEGF及不依赖于VEGF的方式,后者参与介导了抗血管生成治疗中肿瘤抵抗性的形成。此外,髓系细胞还限制了放化疗的治疗效果,促进复发。最后,本文初步探讨了其临床应用前景。     

Inhibitory effects of roxithromycin on tumor angiogenesis, growth and metastasis of mouse B16 melanoma cells

We examined the effects of roxithromycin, a 14-membered ring macrolide antibiotic, on tumor angiogenesis, tumor growth and metastasis of mouse B16BL6 melanoma cells. The inhibitory effect of roxithromycin on angiogenesis using mouse dorsal air sac model was dose-dependent, and 100 mg/kg of roxithromycin administered intraperitoneally twice a day reduced the dense capillary network area to about 20% of the control. Administration of roxithromycin histologically reduced the development of microvessels and mononuclear cell infiltration. In vivo tumor growth studies demonstrated that intraperitoneal administration of roxithromycin at 20 mg/kg/day and 50 mg/kg/day reduced tumor size of B16BL6 melanoma to about 56% and 33% (experiment 1), 71% and 48% (experiment 2) of that in the respective controls. Roxithromycin also significantly inhibited pulmonary metastasis of B16BL6 cells in a spontaneous system. The inhibitory activities of roxithromycin on angiogenesis, tumor growth and metastasis were compared with those of a potent angiogenesis inhibitor, TNP-470. These data demonstrated that roxithromycin has potent antiangiogenic and antitumor effects and might have possible therapeutic applications.     

Implication of tumstatin in tumor progression of human bronchopulmonary carcinomas

The NC1 domain of alpha3 chain of type IV collagen, namely tumstatin, has been shown to display specific anti-angiogenic properties by inhibiting endothelial cells' proliferation and inducing their apoptosis via an interaction with alphavbeta3 integrin. Until now, the tumstatin anti-angiogenic effect has only been shown by in vitro studies or mouse xenograft experiments. In the present study, we examined the expression of tumstatin in relationship with tumor vascularization in 34 bronchopulmonary human carcinomas. We observed a clear association between tumstatin expression and tumor vascularization. Indeed, a strong expression of tumstatin in the tumor environment correlated with a mildly developed vascular network. In contrast, tumstatin was absent or poorly detected in highly vascularized tumors. Moreover, alphavbeta3 integrin and tumstatin colocalized in capillary endothelial cells, suggesting a potential interaction between these 2 molecules. Thus, our results plead in favor of an in vivo anti-angiogenic effect of tumstatin. This factor, largely expressed in well-differentiated lung carcinomas, could indeed reduce tumor vascularization and thereby limit tumor progression.     

Mechanisms of tumor angiogenesis and therapeutic implications: angiogenesis inhibitors

Angiogenesis is the development of new blood vessels from the existing vascular bed. In normal conditions this tightly regulated process occurs only during embryonic development, the female reproductive cycle and wound repair. In contrast, in pathological conditions such as malignant growth, atherosclerosis and diabetic retinopathy, angiogenesis becomes persistent due to an imbalance in the interplay between the positive and negative regulatory signals controlling the process. Thus, the control of tumor neovascularization may lead to new therapeutic approaches. Indeed, several anti-angiogenic drugs are currently undergoing preclinical characterization and/or clinical investigation. Recent achievement has clarified the mechanisms of action leading to pathological angiogenesis and has highlighted the role of hypoxia, growth factors, growth factor-receptors, enzymes and cell adhesion molecules involved in the process. This knowledge has permitted the design of receptor antagonists, adhesion molecule blockers and new targeted vascular approaches including gene therapy.     

羟基红花黄色素A抑制H22小鼠肝癌移植瘤血管生成及减少MMP-3的表达

目的研究红花组分羟基红花黄色素A(HSYA)对H22小鼠肝癌移植瘤组织新血管生成的抑制作用及对基质金属蛋白酶-3(MMP-3)的影响。方法建立H22小鼠肝癌移植瘤模型,第2天将小鼠随机分为对照组、索拉非尼组及HSYA组(1.125和2.25 mg/kg),HE观察肝癌移植瘤组织病理;用免疫组织化学法检测肿瘤组织中CD34的表达,计数微血管密度(MVD);免疫组化和Western blot分别检测瘤组织中MMP-3的表达。结果与对照组相比,HSYA组(1.125和2.25 mg/kg)的MVD显著降低(P0.01),MMP-3蛋白在移植瘤组织中的表达明显减少(P0.01),以HSYA组(2.25 mg/kg)效果最为显著,但不及索拉非尼组。结论 HSYA在一定浓度范围内抑制H22小鼠肝癌移植瘤血管生成,其作用可能与降低基质金属蛋白酶-3的蛋白表达有关。