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胶质瘤血管生成评估模型。

Models for assessment of angiogenesis in gliomas.

作者信息

Goldbrunner R H, Wagner S, Roosen K, Tonn J C

机构信息

Department of Neurosurgery, University of Wuerzburg, Germany.

出版信息

J Neurooncol. 2000 Oct-Nov;50(1-2):53-62. doi: 10.1023/a:1006462504447.

Abstract

In the last two decades, much attention has been focussed on mechanisms of glioma vascularization including the investigation of growth factors and receptors involved. Recently, these efforts resulted in various approaches for antiangiogenic treatment of experimental brain tumors. These basic science and preclinical trials need an assortment of models, which should allow investigating a variety of questions. Several objectives concerning basic endothelial cell (EC) characteristics can adequately be studied in vitro using EC monolayer assays. Three-dimensional spheroid techniques respect the more complex cell-cell and cell-environment interplay within a three-dimensional culture. To optimize the imitation of the crucial interaction of human gliomas with host endothelial cells, immunological cells and extracellular matrix, animal models are mandatory. An essential rule is to utilize an orthotopic model, since tumor-host interaction is organ specific. To avoid alloimmunogenic responses, it is desirable to use weakly or not immunogenic glioma grafts, what is best accomplished in a syngeneic model. However, since rat gliomas poorly resemble human glioma growth patterns, human glioma xenografting into immunocompromized animals should be considered. In vivo monitoring techniques like videoscopy via a cranial window or magnetic resonance imaging (MRI) allow for functional studies and improve the validity of the model employed. Finally, it is essentially to recognize the limitations of each model considered and to select that model, which seems to be most appropriate for the objectives to be investigated.

摘要

在过去二十年中,人们对胶质瘤血管生成机制给予了高度关注,包括对相关生长因子和受体的研究。最近,这些研究成果催生了多种针对实验性脑肿瘤的抗血管生成治疗方法。这些基础科学和临床前试验需要各种各样的模型,以便能够研究各种问题。关于内皮细胞(EC)基本特性的几个目标可以通过体外EC单层试验进行充分研究。三维球体技术考虑到了三维培养中更复杂的细胞间和细胞与环境之间的相互作用。为了优化对人类胶质瘤与宿主内皮细胞、免疫细胞和细胞外基质之间关键相互作用的模拟,动物模型是必不可少的。一个重要原则是使用原位模型,因为肿瘤与宿主的相互作用具有器官特异性。为了避免同种免疫反应,最好使用弱免疫原性或无免疫原性的胶质瘤移植物,这在同基因模型中最容易实现。然而,由于大鼠胶质瘤与人类胶质瘤的生长模式差异较大,因此应考虑将人类胶质瘤异种移植到免疫缺陷动物体内。诸如通过颅骨窗口进行的视频显微镜检查或磁共振成像(MRI)等体内监测技术有助于进行功能研究,并提高所采用模型的有效性。最后,必须认识到所考虑的每个模型的局限性,并选择最适合待研究目标的模型。

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