Importance of hypoxic regions as cancer stem cell niche; in vivo analyses using a novel mouse model
| Project/Area Number |
26670555
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Radiation science
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| Research Institution | Kyoto University |
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Principal Investigator |
Hiraoka Masahiro 京都大学, 医学(系)研究科(研究院), 教授 (70173218)
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| Co-Investigator(Kenkyū-buntansha) |
HARADA Hiroshi 京都大学, 白眉センター, 特定准教授 (80362531)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | がん / 放射線治療 / がん幹細胞 / 低酸素 / HIF-1 / 腫瘍内低酸素 / 放射線抵抗性 |
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| Outline of Final Research Achievements |
Accumulating evidence has suggested that cancer cells acquire radioresistance in hypoxic regions of solid tumors with the help of a transcription factor, HIF-1. However, there is no direct evidence for the involvement of HIF-1-active cancer cells in tumor recurrence after radiotherapy so far. Here, we established a novel system to specifically eliminate HIF-1-active hypoxic cells from a tumor xenograft by combining a HIF-1-dependent promoter (5HRE) with a diphtheria toxin receptor (DTR) and establishing breast cancer cell line, EMT6, with the plasmid (EMT6/5HRE-DTR), and approached the problem. Immunohistochemical analyses demonstrated that, when xenografted into immunodeficient nude mice, the EMT6/5HRE-DTR stable transfectant exhibited TUNEL-positive nuclei after DT treatment in HIF-1-active hypoxic regions. Growth delay assay demonstrated a possibility that the tumor recurrence after radiotherapy is influenced by the elimination of HIF-1-active hypoxic cells from tumor xenografts.
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Report
(3 results)
Research Products
(34 results)
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[Journal Article] UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1alpha2015
Author(s)
Goto Y, Zeng L, YeomCJ, Zhu Y, Morinibu A, Shinoyam K, Kobayashi M, Hirota K, Itasaka S, Yoshimura M, Tanimoto K, Sowa T, Menju T, Sonobe M, Kakeya H, Toi M, Date H, Hammond EM, Hiraoka M, Harada H.
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Journal Title
Nat Commun
Volume: 6
Issue: 1
Pages: 1-10
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Aberrant IDH3α expression promotes malignant tumor growth by inducing HIF-1-mediated metabolic reprogramming and angiogenesis.2014
Author(s)
Zeng L, Morinibu A, Kobayashi M, Zhu Y, Wang X, Goto Y, Yeom CJ, Zhao T,Hirota K, Shinomiya K, Itasaka S, Yoshimura M, Guo G, Hammond EM, Hiraoka M, Harada H.
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Journal Title
Oncogene
Volume: epub
Issue: 36
Pages: 4758-4766
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Near-infraredfluorescence imaging of cancer mediated by tumor hypoxia and HIF1α/OATPs signaling axis.2014
Author(s)
Wu JB, Shao C, Li X, Shi C, Li Q, Hu P, Chen YT, Dou X, Sahu D, Li W, Harada H, Zhang Y, Wang R, Zhau HE, Chung LW.
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Journal Title
Biomaterials
Volume: 35
Issue: 28
Pages: 8175-8185
DOI
Related Report
Peer Reviewed
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