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端粒酶抑制可诱导人星形细胞瘤发生急性 ATM 依赖性生长停滞。

Telomerase inhibition induces acute ATM-dependent growth arrest in human astrocytomas.

作者信息

Wong Vincent C H, Ma Jing, Hawkins Cynthia E

机构信息

Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, Ont., Canada M5G 1X8.

出版信息

Cancer Lett. 2009 Feb 8;274(1):151-9. doi: 10.1016/j.canlet.2008.09.012. Epub 2008 Oct 21.

Abstract

The purpose of the study was to examine the degree of hTERT, the catalytic subunit of telomerase, expression in paediatric high-grade astrocytoma and to explore the potential of telomerase inhibition as a therapy for these tumours. hTERT was expressed at high levels in 36 of 44 paediatric astrocytomas. Telomerase inhibition induced acute DNA damage and ATM-pathway-dependent G2/M cell cycle arrest in astrocytomas in vitro, both occurring prior to telomere shortening itself. Our data suggest that telomerase inhibition could be a useful adjuvant therapy for high-grade astrocytomas, potentially inducing tumour growth arrest following short-term treatment.

摘要

该研究的目的是检测端粒酶的催化亚基hTERT在小儿高级别星形细胞瘤中的表达程度,并探索抑制端粒酶作为这些肿瘤治疗方法的潜力。在44例小儿星形细胞瘤中,有36例hTERT呈高水平表达。在体外,抑制端粒酶可诱导星形细胞瘤发生急性DNA损伤以及ATM通路依赖性G2/M期细胞周期阻滞,这两种情况均发生在端粒自身缩短之前。我们的数据表明,抑制端粒酶可能是高级别星形细胞瘤一种有效的辅助治疗方法,短期治疗后可能诱导肿瘤生长停滞。

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