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当前鉴定神经胶质瘤干细胞的策略:足够或不满意?

Current strategies for identification of glioma stem cells: adequate or unsatisfactory?

机构信息

Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy.

出版信息

J Oncol. 2012;2012:376894. doi: 10.1155/2012/376894. Epub 2012 May 23.

DOI:10.1155/2012/376894
PMID:22685459
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3366252/
Abstract

Cancer stem cells (CSCs) were isolated in multiple tumor types, including human glioblastomas, and although the presence of surface markers selectively expressed on CSCs can be used to isolate them, no marker/pattern of markers are sufficiently robust to definitively identify stem cells in tumors. Several markers were evaluated for their prognostic value with promising early results, however none of them was proven to be clinically useful in large-scale studies, leading to outstanding efforts to identify new markers. Given the heterogeneity of human glioblastomas further investigations are necessary to identify both cancer stem cell-specific markers and the molecular mechanisms sustaining the tumorigenic potential of these cells to develop tailored treatments. Markers for glioblastoma stem cells such as CD133, CD15, integrin-α6, L1CAM might be informative to identify these cells but cannot be conclusively linked to a stem cell phenotype. Overlap of expression, functional state and morphology of different subpopulations lead to carefully consider the techniques employed so far to isolate these cells. Due to a dearth of methods and markers reliably identifying the candidate cancer stem cells, the isolation/enrichment of cancer stem cells to be therapeutically targeted remains a major challenge.

摘要

癌症干细胞 (CSC) 已在多种肿瘤类型中被分离出来,包括人类脑胶质瘤,尽管可以使用选择性表达在 CSC 上的表面标志物来分离它们,但没有一种标志物/标志物模式足够强大,可以明确鉴定肿瘤中的干细胞。已经评估了几种标记物的预后价值,早期结果有希望,但在大规模研究中没有一种被证明具有临床实用性,因此需要付出巨大努力来识别新的标记物。鉴于人类脑胶质瘤的异质性,需要进一步研究以鉴定癌症干细胞特异性标记物和维持这些细胞肿瘤发生潜力的分子机制,以开发针对性的治疗方法。用于鉴定脑胶质瘤干细胞的标志物,如 CD133、CD15、整合素-α6、L1CAM,可能有助于识别这些细胞,但不能明确与干细胞表型相关联。不同亚群的表达、功能状态和形态的重叠导致需要仔细考虑迄今为止用于分离这些细胞的技术。由于缺乏可靠地鉴定候选癌症干细胞的方法和标志物,因此,分离/富集癌症干细胞以进行治疗性靶向仍然是一个主要挑战。

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本文引用的文献

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Self-renewal does not predict tumor growth potential in mouse models of high-grade glioma.自我更新并不能预测高级别神经胶质瘤小鼠模型的肿瘤生长潜力。
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High levels of PROM1 (CD133) transcript are a potential predictor of poor prognosis in medulloblastoma.PROM1(CD133)转录本水平高是成神经管细胞瘤预后不良的潜在预测指标。
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Prognostic impact of CD133 mRNA expression in 48 glioblastoma patients treated with concomitant radiochemotherapy: a prospective patient cohort at a single institution.48 例胶质母细胞瘤患者同期放化疗后 CD133mRNA 表达的预后影响:单中心前瞻性患者队列研究。
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L1CAM regulates DNA damage checkpoint response of glioblastoma stem cells through NBS1.L1CAM 通过 NBS1 调节神经胶质瘤干细胞的 DNA 损伤检查点反应。
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TGF-β Receptor Inhibitors Target the CD44(high)/Id1(high) Glioma-Initiating Cell Population in Human Glioblastoma.TGF-β 受体抑制剂靶向人胶质母细胞瘤中的 CD44(high)/Id1(high) 神经胶质瘤起始细胞群。
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Glioblastoma stem-like cells give rise to tumour endothelium.胶质母细胞瘤干细胞可产生肿瘤内皮细胞。
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Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is reversible and not hierarchically organized.肿瘤发生性黑色素瘤细胞在患者之间存在表型异质性,这种异质性是可逆的,且不是层次组织的。
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Expressions and clinical significances of CD133 protein and CD133 mRNA in primary lesion of gastric adenocacinoma.胃腺癌原发灶中 CD133 蛋白和 CD133mRNA 的表达及其临床意义。
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