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Enhancing the Therapeutic Effects of Low Doses of Ionizing Radiation in Non-Small Cell Lung Cancers Using a Combination of PARP Inhibitors and DNA Demethylating Agents.

机译:使用PARP抑制剂和DNA去甲基化剂的组合增强非小细胞肺癌低剂量电离辐射的治疗效果。

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摘要

Lung cancer (LC) is the leading cause of cancer related deaths and treatment with ionizing radiation (IR) and platinum based DNA damaging agents has had minimal advances. Additionally, patients suffer acute and chronic side-effects due to the high doses of IR that severely limit their quality of life. Therefore, new treatment methods are needed in combination with lower doses of radiation. The Rassool laboratory has recently shown that Poly (ADP-Ribose) Polymerase (PARP) and DNA methyltransferase (DNMT) interact, and inhibition of these proteins increased cytotoxicity in vitro and in vivo in breast, ovarian, and leukemia cancer models. We show here that treatment of LC tumors with both PARP and DNMT inhibitors is effective at reducing viability and clonogenicity, and reducing tumorigenicity in vivo. Moreover, combining the two inhibitors with low radiation doses further decreases tumor growth. This suggests that this therapy can potentially target tumors, while improving effects on normal tissues.
机译:肺癌(LC)是与癌症相关的死亡的主要原因,电离辐射(IR)和铂基DNA破坏剂的治疗进展甚微。此外,由于高剂量的IR严重限制了他们的生活质量,患者会遭受急性和慢性副作用。因此,需要结合较低剂量的放射线的新治疗方法。 Rassool实验室最近发现,聚(ADP-核糖)聚合酶(PARP)和DNA甲基转移酶(DNMT)相互作用,并且在乳腺癌,卵巢癌和白血病癌症模型中,抑制这些蛋白质可提高体内和体外的细胞毒性。我们在这里显示,使用PARP和DNMT抑制剂治疗LC肿瘤可有效降低生存力和克隆性,并降低体内致瘤性。此外,将两种抑制剂与低辐射剂量结合使用可进一步降低肿瘤的生长。这表明该疗法可以潜在地靶向肿瘤,同时改善对正常组织的作用。

著录项

  • 作者单位

    University of Maryland, Baltimore.;

  • 授予单位 University of Maryland, Baltimore.;
  • 学科 Oncology.;Medical imaging.
  • 学位 M.S.
  • 年度 2016
  • 页码 83 p.
  • 总页数 83
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 地球物理学;
  • 关键词

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