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.     

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。     

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。     

肿瘤血管形成机理研究进展

肿瘤血管形成是非常活跃的领域,新进展层出不穷。本文仅就近几年血管形成机理方面的进展进行综述。主要进展包括：内皮细胞表面整合素表达及其调节通路上新的分子机理;调节VEGF／VEGFR通路的新分子机理;内皮细胞表面其他分子活化与血管形成;细胞代谢产物及一些细胞因子、黏附分子通过非常规途径影响内皮细胞迁移;非甾醇类抗炎药物、磺胺药、血管紧张素转化酶抑制剂等老药也在血管形成中扮演新角色;淋巴细胞、浆细胞、单核细胞等也在血管形成过程中发挥特殊作用。     

放疗联合抗血管疗法在肿瘤治疗中的研究进展

随着对肿瘤病理机制的深入了解和放射增敏研究的发展，抗血管治疗联合放疗已成为当前肿瘤治疗研究的热点。Teicher等首先报道抗血管治疗能增加患者对放疗的反应，而后有大量的临床前研究证明抗血管治疗能增加放疗的敏感性。由于新的血管靶向药物的不断问世，许多新的联合治疗方法和结果不断见诸报道。     

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...     

抗血管生成抑制剂疗法研究进展

1　抗血管生成抑制剂的研究　　肿瘤血管形成的主要过程目前认为是:诱发因素→肿瘤细胞被活化分泌可能性血管生成刺激因子,如VEGF(血管内皮生长因子)、FGF(成纤维细胞生长因子)→激活内皮细胞和金属蛋白酶→基底膜被破坏,内皮细胞收缩,趋化,迁移,增殖,形成血管芽→血管芽吻合成血管。因为肿瘤血管及其生长过程的某些特殊性使得其更有利于肿瘤生长和转移,而抗血管生成的所有方法都是靶定内皮细胞而不是肿瘤细胞,这样使得抗血管疗法具有不产生耐药性,而广泛性、毒副作用小等优点。目前抗血管生成抑制剂疗法主要有三种:1.1　“血管生成抑制…     

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…     

DNA疫苗抗肿瘤研究进展

质粒ＤＮＡ或称裸ＤＮＡ疫苗直接肌肉注射后,能表达编码基因的蛋白,并诱导宿主免疫反应。这为肿瘤基因－免疫治疗提供了一种新的途径。近１０年的研究表明,ＤＮＡ疫苗表达质粒骨架中的免疫刺激序列具有佐剂效应和促有丝分裂作用,这与免疫反应的诱导有密切关系。注射部位的肌细胞起着抗原蛋白表达储池作用,通过骨髓来源的抗原呈递细胞,最终诱发宿主体内ＣＴＬ和抗体反应。ＤＮＡ疫苗抗肿瘤的靶向性是由插入表达质粒的编码基因所     

妇科肿瘤围手术期并发下肢深静脉血栓28例诊疗体会

目的探讨妇科肿瘤围手术期并发下肢深静脉血栓的诊断及治疗。方法回顾性分析28例妇科肿瘤围手术期并发下肢深静脉血栓患者的临床资料。结果本组28例患者中恶性肿瘤患者25例，良性肿瘤患者3例，平均年龄51．6岁。经静脉彩色多普勒超声检查并结合D-二聚体监测，确诊后采用全身及局部抗凝、溶栓及活血化淤药物治疗；术前并发中央型、混合型下肢深静脉血栓，及术前或术后并发肺动脉栓塞患者均放置临时性下腔静脉滤器。28例患者均达好转出院，无死亡病例。结论1．妇科肿瘤尤其恶性肿瘤患者围手术期应充分重视LDVT的诊断及治疗。2．下腔静脉滤器可有效预防妇科肿瘤围手术期致命性肺动脉栓塞的发生。     

Efficacy of anti-angiogenic treatment of tumors in old versus young mice

Cancer treatment in the older population, the most afflicted by the disease, is as yet, inefficient. A reduced aggressiveness of tumors is often observed in the elderly, implying the necessity for therapeutic modalities adjusted to age. A rational design of age-related cancer therapy could be based on the mechanisms of this phenomenon. It is suggested that, in addition to the patient's old age-specific health problems (which prohibit the use of the aggressive cancer treatments now in use), the age-related differential tumor biology (apparently beneficial to the old) should also be considered for the design of treatment modalities suitable for the aged. Based on one mechanism of the reduced aggressiveness of tumors in the old (age-dependent decreased angiogenesis), we compared the effect of an anti-angiogenic treatment in young and old mice. TNP-470 treatment resulted in an inhibitory effect on B16 melanoma in both young and old mice but the effect was more pronounced in old animals. Moreover, a high percentage of long-term surviving animals was observed only in the old-treated mice. Treatment with TNP-470 of the AKR lymphoma produced similar results. We thus found a differential age-dependent therapeutic efficiency of an anti-angiogenic agent on two tumors. Importantly, the anti-angiogenic drug was more efficient against tumors of old animals.     

血管生成抑制蛋白vasohibin的研究进展

血管新生参与机体重要的生理和病理过程。Vasohibin是新近发现的调节血管生成的内皮源性负反馈调节因子,对抑制血管生成起重要作用。Vasohibin因参与肿瘤﹑视网膜疾病及类风湿性关节炎等血管新生异常疾病的发生发展而备受关注,相关研究可望为探索这些疾病的发生机制以及寻找新的治疗措施奠定基础。     

Expression of VEGF and VEGFR2 in tumors during neoadjuvant therapy of patients with breast cancer

We revealed a significant positive correlation between the concentrations of tissue VEGF and its receptor VEGFR2 in the primary tumor. The degree and direction of changes in the content of VEGF and VEGFR2 in cytosols of tumors from patients with locally spread breast cancer during the preoperation therapy depended on initial levels of these parameters. We found that the expression of the studied factors depended on the degree of therapeutic pathomorphosis in the tumor tissue. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 2, pp. 206–209, February, 2008     

Molecular addresses of tumors: selection by in vivo phage display

In vivo phage display has been used extensively to screen for novel targets of tumor therapy. Phage display peptide libraries can express random peptides or protein fragments and the aim of phage display is to identify peptide molecules that bind stably to a given target. Angiogenesis is essential to tumor development. Both blood and lymphatic vessels of tumors are different from those of normal tissues. Phage display has been used to analyze the structure and molecular diversity of tumor vasculature and to select tumor-specific antigens which have revealed stage- and type-specific markers of tumor blood vessels. Furthermore, peptides identified by in vivo phage display also work as vehicles to transport cargo therapeutic reagents to tumors. These peptides and their corresponding cellular proteins and ligands may provide molecular tools to selectively target the addresses of tumors and their pathological blood vessels and might increase the efficacy of therapy while decreasing side effects.     

水通道蛋白与肿瘤血管新生

肿瘤血管新生对于肿瘤的生长具有重要作用。水通道蛋白在肿瘤组织中常出现表达异常，并且可以促进肿瘤血管的新生及包括肿瘤血管内皮在内的多种细胞的迁移，与此同时，水通道蛋白与肿瘤血管的高通透性有关，这可能是肿瘤组织对水通道蛋白缺失具有较高敏感性的原因。鉴于水通道蛋白对于肿瘤特别是肿瘤血管新生的影响，其抑制剂可能成为新的肿瘤治疗的目标靶点。     

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.     

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.     

A reinforced random walk model of tumour angiogenesis and anti-angiogenic strategies.

It is now well accepted that the growth of a tumour beyond approximately 2 mm in diameter is dependent on its ability to induce the growth of new blood vessels, a process called angiogenesis. This has raised hope that an anti-angiogenic treatment may be effective in the fight against cancer. Here we formulate, using the theory of reinforced random walks, an individual cell-based mathematical model of tumour angiogenesis in response to a diffusible angiogenic factor. The early stages of angiogenesis, in which endothelial cells (EC) escape the parent vessel and invade the extra-cellular matrix, are included in the model, as are the action of a proteolytic enzyme, EC proliferation and capillary branching and anastomosis. The anti-angiogenic potential of angiostatin, a known inhibitor of angiogenesis, is also examined. The capillary networks predicted by the model are in qualitative agreement with experimental observations. Proteolysis and proliferation are shown to be crucial for vascularization, whilst angiostatin is seen to be capable of limiting capillary growth.