Low Dose Ionizing Radiation Responses and Knockdown of ATM Kinase Activity in Glioma Stem Cells
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概要
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Genesis of new cells in the mammalian brain has previously been regarded as a negligible event; an assumption that long prevented our understanding in the development of neoplasias. The recent discovery of perpetual lineages derived from neural stem cells has resulted in a new approach to studying the cellular behaviour of potential cancer stem cells in the brain. Glioblastoma multiforme (GBM), the most aggressive and lethal brain tumour is derived from such a group of cancerous stem cells known as glioma stem cells. GBM cells are impervious to conventional therapies such as surgical resection and ionizing radiation because of their pluripotent and radioresistant properties. Thus in our study, we aim to investigate whether a combination of chemo- and radio- therapies is an effective treatment for glioma stem cells. The study utilizes a specific kinase inhibitor (ATMi) of the ATM (Ataxia-telangiectasia mutated) protein which is an essential protein in DNA-damage responses. In the presence of both low dose radiation and ATMi, glioma stem cells have rapid onset of cell death and reduction in growth. Since DNA damage can be inherited through cell division, accumulated DNA breaks in later generations may also lead to cell death. The limitation of conventional radiation therapy is that administration of fractionated (low) doses to reduce any potential harm to the surrounding healthy cells in the brain outweighs the benefits of high radiation doses to induce actual arrest in the propagation of malignant cells. Our study demonstrates a benefit in using low dose radiation combined with chemotherapy resulting in a reduction in malignancy of glioma stem cells.
著者
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Yi Chieh
The Queensland Institute of Medical Research, Radiation Biology and Oncology Laboratory
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Roberts Tara
The Queensland Institute of Medical Research, Leukaemia Foundation Laboratory
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Harding Angus
School of Medicine, University of Queensland
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Day Bryan.
Queensland Brain Institute, Neurogenesis Laboratory, University of Queensland
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Yi Chieh
The Queensland Institute Of Medical Research Radiation Biology And Oncology Laboratory
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Day Bryan.
Queensland Brain Institute Neurogenesis Laboratory University Of Queensland
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Roberts Tara
The Queensland Institute Of Medical Research Leukaemia Foundation Laboratory
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Harding Angus
School Of Medicine University Of Queensland
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Lim Yi
The Queensland Institute of Medical Research, Radiation Biology and Oncology Laboratory
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Day Bryan
Queensland Brain Institute, Neurogenesis Laboratory, University of Queensland