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胶质母细胞瘤的细胞与分子机制以及用于发现新疗法的斑马鱼模型

Cellular and Molecular Mechanisms Underlying Glioblastoma and Zebrafish Models for the Discovery of New Treatments.

作者信息

Reimunde Pedro, Pensado-López Alba, Carreira Crende Martín, Lombao Iglesias Vanesa, Sánchez Laura, Torrecilla-Parra Marta, Ramírez Cristina M, Anfray Clément, Torres Andón Fernando

机构信息

Department of Medicine, Campus de Oza, Universidade da Coruña, 15006 A Coruña, Spain.

Department of Neurosurgery, Hospital Universitario Lucus Augusti, 27003 Lugo, Spain.

出版信息

Cancers (Basel). 2021 Mar 3;13(5):1087. doi: 10.3390/cancers13051087.

DOI:10.3390/cancers13051087
PMID:33802571
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7961726/
Abstract

Glioblastoma (GBM) is the most common of all brain malignant tumors; it displays a median survival of 14.6 months with current complete standard treatment. High heterogeneity, aggressive and invasive behavior, the impossibility of completing tumor resection, limitations for drug administration and therapeutic resistance to current treatments are the main problems presented by this pathology. In recent years, our knowledge of GBM physiopathology has advanced significantly, generating relevant information on the cellular heterogeneity of GBM tumors, including cancer and immune cells such as macrophages/microglia, genetic, epigenetic and metabolic alterations, comprising changes in miRNA expression. In this scenario, the zebrafish has arisen as a promising animal model to progress further due to its unique characteristics, such as transparency, ease of genetic manipulation, ethical and economic advantages and also conservation of the major brain regions and blood-brain-barrier (BBB) which are similar to a human structure. A few papers described in this review, using genetic and xenotransplantation zebrafish models have been used to study GBM as well as to test the anti-tumoral efficacy of new drugs, their ability to interact with target cells, modulate the tumor microenvironment, cross the BBB and/or their toxicity. Prospective studies following these lines of research may lead to a better diagnosis, prognosis and treatment of patients with GBM.

摘要

胶质母细胞瘤(GBM)是所有脑恶性肿瘤中最常见的;在目前的标准综合治疗下,其平均生存期为14.6个月。高度异质性、侵袭性和浸润性行为、无法完成肿瘤切除、药物给药限制以及对当前治疗的耐药性是这种疾病所呈现的主要问题。近年来,我们对GBM生理病理学的认识有了显著进展,产生了关于GBM肿瘤细胞异质性的相关信息,包括癌症和免疫细胞,如巨噬细胞/小胶质细胞,以及遗传、表观遗传和代谢改变,包括miRNA表达的变化。在这种情况下,斑马鱼因其独特的特性,如透明度、易于基因操作、伦理和经济优势,以及与人类结构相似的主要脑区和血脑屏障(BBB)的保留,已成为一种有前途的动物模型,可进一步推动研究进展。本综述中描述的几篇论文,使用基因和异种移植斑马鱼模型来研究GBM,以及测试新药的抗肿瘤疗效、它们与靶细胞相互作用的能力、调节肿瘤微环境、穿过BBB的能力和/或它们的毒性。遵循这些研究方向的前瞻性研究可能会带来对GBM患者更好的诊断、预后和治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2945/7961726/21e6666382ca/cancers-13-01087-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2945/7961726/f9f86390f7c3/cancers-13-01087-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2945/7961726/2c689625d90d/cancers-13-01087-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2945/7961726/21e6666382ca/cancers-13-01087-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2945/7961726/f9f86390f7c3/cancers-13-01087-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2945/7961726/2c689625d90d/cancers-13-01087-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2945/7961726/21e6666382ca/cancers-13-01087-g003.jpg

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