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Fractionated radiation-induced nitric oxide promotes expansion of glioma stem-like cells

Authors
 Rae-Kwon Kim  ;  Yongjoon Suh  ;  Yan-Hong Cui  ;  Eunji Hwang  ;  Eun-Jung Lim  ;  Ki-Chun Yoo  ;  Ga-Haeng Lee  ;  Joo-Mi Yi  ;  Seok-Gu Kang  ;  Su-Jae Lee 
Citation
 Cancer Science, Vol.104(9) : 1172-1177, 2013 
Journal Title
 Cancer Science 
ISSN
 1347-9032 
Issue Date
2013
MeSH
Aged ; Brain Neoplasms/genetics ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology* ; Brain Neoplasms/radiotherapy* ; Cell Line, Tumor ; Dose Fractionation ; Down-Regulation ; Drug Resistance, Neoplasm/genetics ; Female ; Glioblastoma/genetics ; Glioblastoma/metabolism ; Glioblastoma/pathology* ; Glioblastoma/radiotherapy* ; Humans ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/metabolism ; Neoplasm Recurrence, Local/pathology ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology* ; Neoplastic Stem Cells/radiation effects* ; Nitric Oxide/biosynthesis* ; Nitric Oxide/genetics ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type II/genetics ; Nitric Oxide Synthase Type II/metabolism ; Radiotherapy/adverse effects ; Up-Regulation
Keywords
Aged ; Brain Neoplasms/genetics ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology* ; Brain Neoplasms/radiotherapy* ; Cell Line, Tumor ; Dose Fractionation ; Down-Regulation ; Drug Resistance, Neoplasm/genetics ; Female ; Glioblastoma/genetics ; Glioblastoma/metabolism ; Glioblastoma/pathology* ; Glioblastoma/radiotherapy* ; Humans ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/metabolism ; Neoplasm Recurrence, Local/pathology ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology* ; Neoplastic Stem Cells/radiation effects* ; Nitric Oxide/biosynthesis* ; Nitric Oxide/genetics ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type II/genetics ; Nitric Oxide Synthase Type II/metabolism ; Radiotherapy/adverse effects ; Up-Regulation
Abstract
Glioblastoma remains an incurable brain disease due to the prevalence of its recurrence. Considerable evidence suggests that glioma stem-like cells are responsible for glioma relapse after treatment, which commonly involves ionizing radiation. Here, we found that fractionated ionizing radiation (2 Gy/day for 3 days) induced glioma stem-like cell expansion and resistance to anticancer treatment such as cisplatin (50 μM) or taxol (500 nM), or by ionizing radiation (10 Gy) in both glioma cell lines (U87, U373) and patient-derived glioma cells. Of note, concomitant increase of nitric oxide production occurred with the radiation-induced increase of the glioma stem-like cell population through upregulation of inducible nitric oxide synthase (iNOS). In line with this observation, downregulation of iNOS effectively reduced the glioma stem-like cell population and decreased resistance to anticancer treatment. Collectively, our results suggest that targeting iNOS in combination with ionizing radiation might increase the efficacy of radiotherapy for glioma treatment.
Full Text
http://onlinelibrary.wiley.com/doi/10.1111/cas.12207/abstract
DOI
10.1111/cas.12207
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Gu(강석구) ORCID logo https://orcid.org/0000-0001-5676-2037
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/87649
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