本帖最后由 jiandong2001 于 2011-1-8 13:56 编辑 3 c: I a# P1 R- z' g, p+ u ' `* [, i; x5 b. B: j' |1.原文来自STEM CELLS 2010;28:1019–1029，由干细胞之家会员jiandong2001翻译。& T+ M" [# z) l" B1 X5 T
2.译文：抑制胶质母细胞瘤Notch信号通路可通过内皮细胞介导靶向作用于肿瘤干细胞2 T) ~4 F3 J- k/ q( S 摘要：胶质母细胞瘤（GBM）是一种高度异质性的恶性肿瘤。近来的研究资料提示GBM细胞中存在等级性的细胞，包括具有类似干细胞样性质的的肿瘤细胞，可重新形成肿瘤并与治疗耐药有关。肿瘤干细胞被认为存在于可提供结构及功能支持的血管微环境中。然而，多数有关GBM的研究在不同的培养条件下分离肿瘤细胞。本文中，作者使用了一种新的三维的器官样的“体外移植”体系，用于培养外科手术获得的GBM标本，这种标本保留了细胞结构与肿瘤间质及肿瘤细胞的关系。体外移植物Notch信号通路的抑制导致了肿瘤细胞增殖及自我更新的下降，同时也减少了内皮细胞。当使用偶联的毒性物质选择性清除体外移植物内皮细胞的时候，同样也观察到了肿瘤干细胞自我更新的下调。这一发现支持了肿瘤内皮细胞在GBM干细胞维持中的重要作用，至少部分经由Notch信号通路调节。体外移植物体系还进一步突出了其与分离的肿瘤细胞球对放疗应答的差别。联合使用阻断Notch通路与放疗的方法可从根本上降低体外移植肿瘤细胞的增殖与自我更新能力，而单独使用放射治疗则要差很多。这些数据提示Notch信号通路在联系血管生成与肿瘤干细胞自我更新中起着重要的作用，因而可成为一个潜在的治疗靶点。三维体外移植体系则提供了一种新的途径用于研究肿瘤与微环境的相互作用。& K, \! B1 W2 ? a4 _
3.原文：Inhibition of Notch Signaling in Glioblastoma Targets Cancer Stem Cells via an Endothelial Cell Intermediate , e- q$ ]- z+ } ABSTRACT Glioblastoma multiforme (GBM) is a highly heterogeneous malignant tumor. Recent data suggests the presence of a hierarchical organization within the GBM cell population that involves cancer cells with stem-like behavior, capable of repopulating the tumor and contributing to its resistance to therapy. Tumor stem cells are thought to reside within a vascular niche that provides structural and functional support. However, most GBM studies involve isolated tumor cells grown under various culture conditions. Here, we use a novel three-dimensional organotypic ‘‘explant’’ system of surgical GBM specimens that preserves cytoarchitecture and tumor stroma along with tumor cells. Notch inhibition in explants results in decreased proliferation and self-renewal of tumor cells but is also associated with a decrease in endothelial cells. When endothelial cells are selectively eliminated from the explants via a toxin conjugate, we also observed a decrease in self-renewal of tumor stem cells. These findings support a critical role for tumor endothelial cells in GBM stem cell maintenance, mediated at least in part by Notch signaling. The explant system further highlighted differences in the response to radiation between explants and isolated tumor neurospheres. Combination treatment with Notch blockade and radiation resulted in a substantial decrease in proliferation and in self-renewal in tumor explants while radiation alone was less effective. This data suggests that the Notch pathway plays a critical role in linking angiogenesis and cancer stem cell self-renewal and is thus a potential therapeutic target. Three-dimensional explant systems provide a novel approach for the study of tumor and microenvironment interactions. _9 I5 J1 m9 P6 [
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