Basic research for the optimization of stereotactic radiotherapy

• Project/Area Number: 24659563
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Kyoto University
• Principal Investigator: ITASAKA SATOSHI 京都大学, 医学(系)研究科(研究院), 非常勤講師 (90378654)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 放射線治療 / 腫瘍内低酸素 / 定位放射線治療

Outline of Final Research Achievements

In this study, changes of intra-tumoral hypoxia, HIF-1 activity, and vasculature after a large dose single irradiation were evaluated, sequentially. Effects of large dose irradiation on tumors and normal tissues were evaluated at the same time. It was also tried to find factors that enhance the therapeutic effects. Human lung cancer cell line H441 transfected with HIF-1 responsible luciferase gene were implanted into the nude mice, subcutaneously. The temporal changes of intra-tumoral hypoxia were observed as HIF-1 activity change by optical imaging. Optimal timing of the second irradiation was evaluated using the HIF-1 imaging to maximize the therapeutic effects of irradiation. We could not identify new therapeutic targets that can enhance the effect of radiation therapy.

Research Products

• [Journal Article] UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1alpha (2015)
  • 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.
  • Journal Title: Nat Commun Volume: 6 Issue: 1 Pages: 1-10
  • DOI: 10.1038/ncomms7153
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: Oncogene Volume: epub Issue: 36 Pages: 4758-4766
  • DOI: 10.1038/onc.2014.411
  • Peer Reviewed / Open Access
• [Journal Article] HIF-1-mediated metabolic reprogramming reduces ROS levels and facilitates the metastatic colonization of cancers in lungs. (2014)
  • Author(s): 1. Zhao T, Zhu Y, Morinibu A, Kobayashi M, Shinomiya K, Itasaka S, Yoshimura M, Guo G, Hiraoka M, Harada H.
  • Journal Title: Scientific Reports Volume: 4.3793 Issue: 1 Pages: 1-7
  • DOI: 10.1038/srep03793
  • Peer Reviewed / Open Access
• [Journal Article] Microenvironment and radiation therapy (2013)
  • Author(s): M Yoshimura, S Itasaka, H Harada,
  • Journal Title: Biomed Res Int Volume: 2013 Pages: 685308-685308
  • DOI: 10.1155/2013/685308
  • NAID: 120005243745
  • Peer Reviewed
• [Journal Article] Evaluation of novel orthotopic nude mouse models for human small-cell lung cancer (2013)
  • Author(s): T Isobe, A Onn, D Morgensztern, JJ Jacoby, W Wu, T Shintani, S Itasaka, K Shibuya, PJ Koo, MS O'Reilly, RS Herbst
  • Journal Title: J Thorac Oncol Volume: 8(2) Issue: 2 Pages: 140-6
  • DOI: 10.1097/jto.0b013e3182725ff9
  • Peer Reviewed