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Aberrant Signaling in Astrocytomas and Glioblastoma Multiforme (GBM): Utilizing Inhibitors of Proliferation as Potential Therapies.

机译:星形细胞瘤和胶质母细胞瘤(GBM)中的异常信号:利用增殖抑制剂作为潜在疗法。

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摘要

Glioblastomas (GBMs), the most aggressive malignant astrocytomas, are recurrent, infiltrative, and fatal. In GBMs, receptor tyrosine kinases (RTKs) are often activated by mutations, leading to the dysregulation of cell signaling pathways. The PI3K/Akt1/mTOR pathway, which plays a role in many biological processes such as proliferation, survival, invasion, migration and angiogenesis, is often deregulated in malignant cancers, often by the simultaneous loss of tumor suppressor PTEN, and the hyperactivation of the kinase Akt. Therefore, pharmacological inhibition of the PI3K/Akt1/mTOR pathway may prove beneficial in arresting the growth of astrocytomas and glioblastomas. In order to determine if the candidate molecules Choloroquine, Nelfinivir, PIA-6, OSU03012, Rapamycin, Tricribine (TCN), and PI-103 inhibit the PI3K/Akt-1/mTOR pathway, we used the Alamar blue assay as a measure of cell viability and cytotoxicity in mouse astrocytoma cell lines K1861-10 Grade II; KR158 Grade III; K130G
机译:胶质母细胞瘤(GBMs)是最具侵袭性的恶性星形细胞瘤,复发,浸润和致命。在GBM中,受体酪氨酸激酶(RTK)通常被突变激活,从而导致细胞信号通路的失调。 PI3K / Akt1 / mTOR通路在许多生物学过程中发挥作用,例如增殖,存活,侵袭,迁移和血管生成,在恶性肿瘤中常常被调节失调,通常是由于肿瘤抑制因子PTEN的同时丧失和PTEN的过度活化。激酶Akt。因此,对PI3K / Akt1 / mTOR途径的药理抑制作用可能在阻止星形细胞瘤和胶质母细胞瘤的生长方面被证明是有益的。为了确定候选分子Choloroquine,Nelfinivir,PIA-6,OSU03012,Rapamycin,Tricribine(TCN)和PI-103是否抑制PI3K / Akt-1 / mTOR途径,我们使用了Alamar蓝测定法来衡量小鼠星形细胞瘤细胞系K1861-10 II级的细胞活力和细胞毒性; KR158 III级; K130G

著录项

  • 作者

    Connell-Albert, Yvette S.;

  • 作者单位

    George Mason University.;

  • 授予单位 George Mason University.;
  • 学科 Biology Molecular.;Health Sciences Oncology.
  • 学位 Ph.D.
  • 年度 2013
  • 页码 200 p.
  • 总页数 200
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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