Neurosphere formation is an independent predictor of clinical outcome in malignant glioma.
Neurosphere formation is an independent predictor of clinical outcome in malignant glioma.
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DOI：
10.1002/stem.15
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发表时间：
2009-04
期刊：
影响因子：
5.2
通讯作者：
Kornblum, Harley I.
中科院分区：
文献类型：
--
作者：
Laks, Dan R.;Masterman-Smith, Michael;Visnyei, Koppany;Angenieux, Brigitte;Orozco, Nicholas M.;Foran, Ian;Yong, William H.;Vinters, Harry V.;Liau, Linda M.;Lazareff, Jorge A.;Mischel, Paul S.;Cloughesy, Timothy F.;Horvath, Steve;Kornblum, Harley I.
关键词：
培养中可再生神经球的形成是某些脑肿瘤起始细胞的定义特征。这项回顾性研究旨在评估培养的人脑胶质瘤中神经球形成、致瘤能力和患者临床结局之间的关系。在神经球条件下培养来自32名神经胶质瘤患者的肿瘤样品，包括15名原发性胶质母细胞瘤患者的亚群。将可再生神经球培养物的子样品异种移植到小鼠脑中以确定它们是否是致瘤性的。我们的研究表明，可再生神经球的形成和致瘤能力与临床结果指标显著相关。培养的人脑胶质瘤中可再生神经球的形成显著预测了患者死亡风险的增加和肿瘤进展的更快。这些结果涉及神经胶质瘤的全部人群和原发性胶质母细胞瘤的亚群。同样，对于具有致瘤能力的胶质瘤患者，存在显著的进展风险。多变量分析表明，神经球形成仍然是独立于Ki67增殖指数的临床结果的重要预测因子。此外，神经球形成、肿瘤分级和患者年龄的多变量分析表明，神经球形成是神经胶质瘤肿瘤进展的一个可靠的独立预测因子。虽然该试验的持续时间较长，可能无法直接应用于临床，但这些结果表明神经球培养如何作为恶性胶质瘤研究的临床相关模型。此外，这项研究表明，脑肿瘤干细胞在体外增殖的能力与临床结果有关。
Renewable neurosphere formation in culture is a defining characteristic of certain brain tumor initiating cells. This retrospective study was designed to assess the relationship between neurosphere formation in cultured human glioma, tumorigenic capacity, and patient clinical outcome. Tumor samples were cultured in neurosphere conditions from 32 patients with glioma, including a subpopulation of 15 patients with primary glioblastoma. A subsample of renewable neurosphere cultures was xenografted into mouse brain to determine if they were tumorigenic. Our study shows that both renewable neurosphere formation and tumorigenic capacity are significantly associated with clinical outcome measures. Renewable neurosphere formation in cultured human glioma significantly predicted an increased hazard of patient death and more rapid tumor progression. These results pertained to both the full population of glioma and the subpopulation of primary glioblastoma. Similarly, there was a significant hazard of progression for patients whose glioma had tumorigenic capacity. Multivariate analysis demonstrated that neurosphere formation remained a significant predictor of clinical outcome independent of Ki67 proliferation index. In addition, multivariate analysis of neurosphere formation, tumor grade and patient age, demonstrated that neurosphere formation was a robust, independent predictor of glioma tumor progression. While the lengthy duration of this assay may preclude direct clinical application, these results exemplify how neurosphere culture serves as a clinically relevant model for the study of malignant glioma. Furthermore, this study suggests that the ability to propagate brain tumor stem cells in vitro is associated with clinical outcome.
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影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
影响因子：
50.3
作者：
Phillips, HS;Kharbanda, S;Aldape, K
通讯作者：
Aldape, K
影响因子：
4.2
作者：
Nakano, Ichiro;Masterman-Smith, Michael;Kornblum, Harley I.
通讯作者：
Kornblum, Harley I.
影响因子：
11.2
作者：
Galli, R;Binda, E;Vescovi, A
通讯作者：
Vescovi, A
DOI：
10.1073/pnas.77.2.1039
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
CIFONE, MA;FIDLER, IJ
通讯作者：
FIDLER, IJ