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首页> 外文学位 >Poly-ADP-Ribose-Polymerase as a Therapeutic Target in Paediatric Diffuse Intrinsic Pontine Glioma and Paediatric High Grade Astrocytoma.
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Poly-ADP-Ribose-Polymerase as a Therapeutic Target in Paediatric Diffuse Intrinsic Pontine Glioma and Paediatric High Grade Astrocytoma.

机译：聚-ADP-核糖聚合酶作为小儿弥漫性固有性脑胶质瘤和小儿高级星形细胞瘤的治疗靶标。

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摘要

Paediatric high-grade astrocytomas (pHGA) and diffuse-intrinsic-pontine-gliomas (DIPG) are devastating paediatric malignancies for which there are no effective therapies. Previous evidence found Poly-ADP-Ribose-Polymerase 1 (PARP1) over-expressed in DIPG and pHGA. Immunohistochemical and western-blot analysis was performed on pHGA and DIPG patient tumour samples and cell lines to establish PARP1 expression. Three PARP inhibitors, Veliparib, Olaparib, and Niraparib, were used to study PARP inhibition in multiple pHGA and DIPG cell lines and intracranial xenografts. PARP1 was expressed in the majority of pHGA and DIPG patient samples and cell lines and PARP inhibition in vitro resulted in growth arrest and/or apoptosis. Niraparib was the most effective monotherapeutic agent. Niraparib reduced the rate of DNA repair and sensitized cells in vitro to ionizing radiation (IR). In vivo, Niraparib when combined with IR, inhibited PARP1 and extended survival by 40%. Therefore, PARP1 may serve as a potential therapeutic target in pHGA and DIPG.
机译：儿科高级星形细胞瘤（pHGA）和弥漫性桥脑神经胶质瘤（DIPG）是破坏性的小儿恶性肿瘤，目前尚无有效的治疗方法。先前的证据发现DIPG和pHGA中过表达的Poly-ADP-核糖聚合酶1（PARP1）。对pHGA和DIPG患者的肿瘤样品和细胞系进行了免疫组织化学和蛋白质印迹分析，以建立PARP1表达。三种PARP抑制剂Veliparib，Olapaparib和Niraparib用于研究多种pHGA和DIPG细胞系以及颅内异种移植物中的PARP抑制作用。 PARP1在大多数pHGA和DIPG患者样品和细胞系中表达，体外PARP抑制导致生长停滞和/或凋亡。 Niraparib是最有效的单药治疗药物。 Niraparib降低了DNA修复率，并使体外细胞对电离辐射（IR）敏感。在体内，尼拉帕单抗与IR联用可抑制PARP1并延长生存期40％。因此，PARP1可以作为pHGA和DIPG中潜在的治疗靶标。

著录项

  • 作者

    Chornenkyy, Yevgen.;

  • 作者单位

    University of Toronto (Canada).;

  • 授予单位 University of Toronto (Canada).;
  • 学科 Biology.
  • 学位 M.Sc.
  • 年度 2015
  • 页码 76 p.
  • 总页数 76
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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