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涉及多形性胶质母细胞瘤放射抵抗的分子途径:细胞外囊泡的作用是什么?

Molecular Pathways Implicated in Radioresistance of Glioblastoma Multiforme: What Is the Role of Extracellular Vesicles?

机构信息

Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90133 Palermo, Italy.

Department of Human Anatomy, Institute of Medicine, Penza State University, 440026 Penza, Russia.

出版信息

Int J Mol Sci. 2023 Mar 2;24(5):4883. doi: 10.3390/ijms24054883.

Abstract

Glioblastoma multiforme (GBM) is a primary brain tumor that is very aggressive, resistant to treatment, and characterized by a high degree of anaplasia and proliferation. Routine treatment includes ablative surgery, chemotherapy, and radiotherapy. However, GMB rapidly relapses and develops radioresistance. Here, we briefly review the mechanisms underpinning radioresistance and discuss research to stop it and install anti-tumor defenses. Factors that participate in radioresistance are varied and include stem cells, tumor heterogeneity, tumor microenvironment, hypoxia, metabolic reprogramming, the chaperone system, non-coding RNAs, DNA repair, and extracellular vesicles (EVs). We direct our attention toward EVs because they are emerging as promising candidates as diagnostic and prognostication tools and as the basis for developing nanodevices for delivering anti-cancer agents directly into the tumor mass. EVs are relatively easy to obtain and manipulate to endow them with the desired anti-cancer properties and to administer them using minimally invasive procedures. Thus, isolating EVs from a GBM patient, supplying them with the necessary anti-cancer agent and the capability of recognizing a specified tissue-cell target, and reinjecting them into the original donor appears, at this time, as a reachable objective of personalized medicine.

摘要

多形性胶质母细胞瘤(GBM)是一种原发性脑肿瘤,具有很强的侵袭性、对治疗有抵抗力,并且具有高度的间变和增殖特征。常规治疗包括消融手术、化疗和放疗。然而,GBM 会迅速复发并产生放射抗性。在这里,我们简要回顾了放射抗性的机制,并讨论了阻止放射抗性和安装抗肿瘤防御的研究。参与放射抗性的因素多种多样,包括干细胞、肿瘤异质性、肿瘤微环境、缺氧、代谢重编程、伴侣蛋白系统、非编码 RNA、DNA 修复和细胞外囊泡(EVs)。我们将注意力集中在 EVs 上,因为它们作为诊断和预后工具以及作为开发用于将抗癌剂直接递送到肿瘤块的纳米器件的基础,正在成为有前途的候选物。EVs 相对容易获得和操作,可赋予它们所需的抗癌特性,并通过微创程序进行给药。因此,从 GBM 患者中分离 EVs,为它们提供必要的抗癌剂和识别特定组织细胞靶标的能力,并将它们重新注入原始供体,目前似乎是个性化医疗的一个可实现的目标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d947/10003080/bafd8e6de34f/ijms-24-04883-g001.jpg

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