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从床边到实验台:基于近期分类更新及脑肿瘤网络动物模型对癫痫相关肿瘤的新见解

From bedside to bench: New insights in epilepsy-associated tumors based on recent classification updates and animal models on brain tumor networks.

作者信息

Cases-Cunillera Silvia, Friker Lea L, Müller Philipp, Becker Albert J, Gielen Gerrit H

机构信息

INSERM U1266, Neuronal Signaling in Epilepsy and Glioma, Institute of Psychiatry and Neuroscience of Paris (IPNP), Université Paris Cité, Paris, France.

Section for Translational Epilepsy Research, Institute of Neuropathology, University Hospital Bonn, Bonn, Germany.

出版信息

Mol Oncol. 2024 Dec;18(12):2951-2965. doi: 10.1002/1878-0261.13680. Epub 2024 Jun 20.

DOI:10.1002/1878-0261.13680
PMID:38899375
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11619802/
Abstract

Low-grade neuroepithelial tumors (LGNTs), particularly those with glioneuronal histology, are highly associated with pharmacoresistant epilepsy. Increasing research focused on these neoplastic lesions did not translate into drug discovery; and anticonvulsant or antitumor therapies are not available yet. During the last years, animal modeling has improved, thereby leading to the possibility of generating brain tumors in mice mimicking crucial genetic, molecular and immunohistological features. Among them, intraventricular in utero electroporation (IUE) has been proven to be a valuable tool for the generation of animal models for LGNTs allowing endogenous tumor growth within the mouse brain parenchyma. Epileptogenicity is mostly determined by the slow-growing patterns of these tumors, thus mirroring intrinsic interactions between tumor cells and surrounding neurons is crucial to investigate the mechanisms underlying convulsive activity. In this review, we provide an updated classification of the human LGNT and summarize the most recent data from human and animal models, with a focus on the crosstalk between brain tumors and neuronal function.

摘要

低级别神经上皮肿瘤(LGNTs),尤其是那些具有神经胶质神经元组织学特征的肿瘤,与药物抵抗性癫痫高度相关。针对这些肿瘤性病变的研究日益增多,但尚未转化为药物研发成果;目前尚无抗惊厥或抗肿瘤疗法。在过去几年中,动物模型得到了改进,从而使得在小鼠体内生成模仿关键遗传、分子和免疫组织学特征的脑肿瘤成为可能。其中,子宫内脑室电穿孔(IUE)已被证明是生成LGNTs动物模型的一种有价值的工具,它能使肿瘤在小鼠脑实质内自然生长。癫痫ogenicity主要由这些肿瘤的缓慢生长模式决定,因此反映肿瘤细胞与周围神经元之间的内在相互作用对于研究惊厥活动的潜在机制至关重要。在这篇综述中,我们提供了人类LGNT的最新分类,并总结了来自人类和动物模型的最新数据,重点关注脑肿瘤与神经元功能之间的相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0593/11619802/e646a9391acb/MOL2-18-2951-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0593/11619802/1cbe29097c3f/MOL2-18-2951-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0593/11619802/e646a9391acb/MOL2-18-2951-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0593/11619802/1cbe29097c3f/MOL2-18-2951-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0593/11619802/e646a9391acb/MOL2-18-2951-g003.jpg

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Molecular Profiling in Neuro-Oncology: Where We Are, Where We're Heading, and How We Ensure Everyone Can Come Along.神经肿瘤学中的分子谱分析:我们身在何处,我们将去往何方,以及我们如何确保每个人都能参与其中。
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Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology.
多组学生物标志物神经病理学提高儿科神经肿瘤学的诊断准确性。
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Low-grade epilepsy-associated neuroepithelial tumors: Tumor spectrum and diagnosis based on genetic alterations.低级别癫痫相关神经上皮肿瘤:基于基因改变的肿瘤谱及诊断
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Neurochemical Profile of BRAFV600E/AktT308D/S473D Mouse Gangliogliomas Reveals Impaired GABAergic System Inhibition.BRAFV600E/AktT308D/S473D 基因突变型小鼠神经节神经胶质瘤的神经化学特征显示 GABA 能系统抑制受损。
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