Targeting Brain Tumor Stem Cells with Oncolytic Adenoviruses
Targeting Brain Tumor Stem Cells with Oncolytic Adenoviruses
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DOI：
10.1007/978-1-61779-340-0_9
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Fueyo, Juan
中科院分区：
文献类型：
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作者：
Alonso, Marta M.;Jiang, Hong;Fueyo, Juan
在2004年，脑肿瘤干细胞（BTSC）从外科手术的人类恶性神经胶质瘤中分离。这种癌细胞群已被确定为肿瘤起始和对治疗耐药的根源。因此，必须开发新的治疗方法，可以根除这一亚群，以改善脑肿瘤患者的预后。我们的小组先前报道了肿瘤选择性溶瘤腺病毒Delta-24-RGD的抗胶质瘤作用，目前正在对恶性胶质瘤患者进行I期临床试验。我们还表明，Delta-24-RGD感染，复制，并诱导BTSC中的细胞死亡。有趣的是，我们观察到腺病毒感染的细胞经历自噬，自噬相关的胞质空泡化可能是旧的溶解过程的一部分。在此，我们总结了本研究中使用的材料和方法，包括：从人多形性胶质母细胞瘤手术标本中建立神经球培养物;评估干细胞标志物;检查BTSC中的腺病毒受体;评估溶瘤腺病毒诱导的细胞毒性;以及体外溶瘤腺病毒感染的BTSC中自噬的评估，最后，我们描述了一种检测用Delta-24-RGD处理的肿瘤中自噬相关蛋白Atg 5上调的方法。
In 2004, brain tumor stern cells (BTSCs) were isolated from surgical human malignant gliomas. This cancer cell population has been identified as the root for tumor initiation and resistance to therapies. Thus, it is imperative to develop new therapies that can eradicate this subpopulation to improve the prognosis of patients with brain tumors. Our group previously reported the antiglioma effect of the tumor-selective oncolytic adenovirus Delta-24-RGD that is now being tested in a phase I clinical trial for patients with malignant gliomas. We also showed that Delta-24-RGD infects, replicates in, and induces cell death in BTSCs. Interestingly, we observed that adenoviral-infected cells undergo autophagy and that autophagy-related cytoplasmic vacuolization might be part oldie lysis process. Here, we summarize the materials and methods used in our study as follows: establishment of neurosphere cultures from surgical samples of human glioblastoma multiformes; assessment of stem cell markers; examination of adenoviral receptors in BTSCs; evaluation of the cytotoxicity induced by oncolytic adenoviruses; and assessment of autophagy in oncolytic adenovirus-infected BTSCs in vitro, and finally we describe a method to detect upregulation of the autophagy-related protein Atg5 in tumors treated with Delta-24-RGD.