Contributions to drug resistance in glioblastoma derived from malignant cells in the sub-ependymal zone.

Contributions to drug resistance in glioblastoma derived from malignant cells in the sub-ependymal zone.
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DOI:
10.1158/0008-5472.can-13-3131
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发表时间:
2015-01-01
期刊:
影响因子:
11.2
通讯作者:
Watts C
Watts C
中科院分区:
医学1区
文献类型:
--
作者:
Piccirillo SG;Spiteri I;Sottoriva A;Touloumis A;Ber S;Price SJ;Heywood R;Francis NJ;Howarth KD;Collins VP;Venkitaraman AR;Curtis C;Marioni JC;Tavaré S;Watts C

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胶质母细胞瘤(GB)是最常见和最具侵袭性的成人脑肿瘤,其特征在于极端的表型多样性和治疗失败。通过荧光引导切除,我们确定了GB患者室管膜下区(SEZ)的荧光组织。组织学分析和基因组表征显示,SEZ窝藏具有肿瘤起始能力的恶性细胞,类似于从荧光肿瘤块(T)分离的细胞。我们观察到对超大化疗剂量的耐药性沿着T和SEZ在同一肿瘤中的不同药物反应模式。我们的研究结果揭示了GB生长动力学的新见解,对理解和限制治疗抗性具有重要意义。
Glioblastoma (GB), the most common and aggressive adult brain tumor, is characterized by extreme phenotypic diversity and treatment failure. Through fluorescence-guided resection, we identified fluorescent tissue in the sub-ependymal zone (SEZ) of GB patients. Histological analysis and genomic characterization revealed that the SEZ harbors malignant cells with tumor-initiating capacity, analogous to cells isolated from the fluorescent tumor mass (T). We observed resistance to supra-maximal chemotherapy doses along with differential patterns of drug response between T and SEZ in the same tumor. Our results reveal novel insights into GB growth dynamics, with implications for understanding and limiting treatment resistance.