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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >Cellular immortality in brain tumours: an integration of the cancer stem cell paradigm.
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Cellular immortality in brain tumours: an integration of the cancer stem cell paradigm.

机译：脑肿瘤中的细胞永生：癌症干细胞范例的整合。

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Brain tumours are a diverse group of neoplasms that continue to present a formidable challenge in our attempt to achieve curable intervention. Our conceptual framework of human brain cancer has been redrawn in the current decade. There is a gathering acceptance that brain tumour formation is a phenotypic outcome of dysregulated neurogenesis, with tumours viewed as abnormally differentiated neural tissue. In relation, there is accumulating evidence that brain tumours, similar to leukaemia and many solid tumours, are organized as a developmental hierarchy which is maintained by a small fraction of cells endowed with many shared properties of tissue stem cells. Proof that neurogenesis persists throughout adult life, compliments this concept. Although the cancer cell of origin is unclear, the proliferative zones that harbour stem cells in the embryonic, post-natal and adult brain are attractive candidates within which tumour-initiation may ensue. Dysregulated, unlimited proliferation and an ability to bypass senescence are acquired capabilities of cancerous cells. These abilities in part require the establishment of a telomere maintenance mechanism for counteracting the shortening of chromosomal termini. A strategy based upon the synthesis of telomeric repeat sequences by the ribonucleoprotein telomerase, is prevalent in approximately 90% of human tumours studied, including the majority of brain tumours. This review will provide a developmental perspective with respect to normal (neurogenesis) and aberrant (tumourigenesis) cellular turnover, differentiation and function. Within this context our current knowledge of brain tumour telomere/telomerase biology will be discussed with respect to both its developmental and therapeutic relevance to the hierarchical model of brain tumourigenesis presented by the cancer stem cell paradigm.
机译：脑肿瘤是各种各样的肿瘤，它们在我们试图实现可治愈的干预中继续面临着巨大的挑战。在最近十年中，我们对人脑癌的概念框架进行了重新设计。人们日益接受大脑肿瘤的形成是神经发生失调的表型结果，肿瘤被视为异常分化的神经组织。与此相关的是，越来越多的证据表明，类似于白血病和许多实体瘤的脑肿瘤被组织为一个发育等级，由一小部分具有组织干细胞共有特性的细胞所维持。神经生成在整个成年生活中持续存在的证据补充了这一概念。尽管癌细胞的来源尚不清楚，但在胚胎，出生后和成年大脑中藏有干细胞的增殖区是诱人的候选物，在其中可能会引发肿瘤。失调，无限增殖以及绕过衰老的能力是癌细胞的获得能力。这些能力部分地需要建立端粒维持机制以抵消染色体末端的缩短。基于核糖核蛋白端粒酶合成端粒重复序列的策略在大约90％的人类肿瘤（包括大部分脑肿瘤）中普遍存在。这项审查将提供有关正常（神经发生）和异常（肿瘤发生）细胞更新，分化和功能的发展前景。在此背景下，我们将就脑肿瘤端粒/端粒酶生物学的当前发展知识和与癌症干细胞范式呈现的脑肿瘤发生分级模型的治疗相关性进行讨论。

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