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髓母细胞瘤和其他胚胎性脑肿瘤在形态和分化上同神经干细胞和祖细胞相似。通过人类肿瘤标本的基因表达研究和转基因鼠模型分析,提示多能外胚层小脑干细胞和谱系限制性的祖细胞可以通过基因的改变转化为髓母细胞瘤。这些分子的改变常常涉及到Wnt、Hedgehog和Notch等信号通路的组成性激活,这些信号通路在非肿瘤性神经干细胞中发挥重要作用。通过药物阻断Hedgehog和Notch信号通路在体外培养和体内均可抑制髓母细胞瘤的生长,这个可以证明对于肿瘤的发生和长期增殖所必须的小肿瘤干细胞亚群以上述信号通路为靶点阻滞是有效的。
Medulla and other embryonic brain tumors are similar in morphology and differentiation to neural stem and progenitor cells. Gene expression studies in human tumor specimens and transgenic mouse models suggest that pluripotent ectodermal stem cells and lineage-restricted progenitor cells can be converted to medulloblastomas by genetic alterations. These molecular changes often involve constitutive activation of Wnt, Hedgehog and Notch signaling pathways that play an important role in non-neoplastic neural stem cells. The blockade of Hedgehog and Notch signaling by drugs inhibits the growth of medulloblastoma in vitro and in vivo, demonstrating that the small subpopulation of cancer stem cells necessary for tumorigenesis and long-term proliferation is targeted by these signaling pathways Hysteresis is effective.