New treatment for cancer metastasis targeting tumor hypoxia

2011 Fiscal Year Final Research Report

• Project/Area Number: 22791190
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Radiation science
• Research Institution: Kyoto University
• Principal Investigator: ITASAKA Satoshi 京都大学, 医学研究科, 助教 (90378654)
• Project Period (FY): 2010 – 2011
• Keywords: 放射線治療生物学 / 転移 / 放射線治療 / 低酸素 / イメージング / 肺転移モデル

Research Abstract

We have developed the mouse lung metastasis model that allows us to monitor intra-tumor hypoxia during the formation of lung metastasis. We found that progress of lung metastasis was accelerated by transient up-regulation of HIF-1 activity that was dependent upon reactive oxygen species(ROS). This lead to a cellular metabolic reprogramming, that is a change from mitochondrial oxidative phosphorylation to lactic acid fermentation. The use of HIF-1 inhibitor significantly decreased the formation of lung metastasis.

Research Products

• [Journal Article] Clinical practice and outcome of radiotherapy for esophageal cancer between 1999 and 2003 (2012)
  • Author(s): Nishimura Y, Koike R, Ogawa K, Sasamoto R, Murakami Y, Itoh Y, Negoro Y, Itasaka S, Sakayauchi T, Tamamoto T.
  • Journal Title: International Journal of Clincal Oncology Volume: 17(1) Pages: 48-54
  • DOI: DOI:10.1007/s10147-011-0254-y
• [Journal Article] Delayed initial radioactive iodine therapy resulted in poor survival in patients with metastatic differentiated thyroid carcinomaa retrospective statistical analysis of 198 cases (2011)
  • Author(s): Higashi T, Nishii R, Yamada S, Nakamoto Y, Ishizu K, Kawase S, Togashi K, Itasaka S, Hiraoka M, Misaki T, Konishi J.
  • Journal Title: The Journal of Nuclear Medicine Volume: 52(5) Pages: 683-689
  • DOI: DOI:10.2967/jnumed.110.081059
• [Journal Article] A novel strategy to tag matrix metalloproteinases-positive cells for in vivo imaging of invasive and metastatic a ctivity of tumor cells (2010)
  • Author(s): Zhao T, Harada H, Teramura Y, Tanaka SItasaka S, Morinibu A, Shinomiya K, Zhu Y, Hanaoka H, Iwata H, Saji H, Hiraoka M
  • Journal Title: Journal of Controlled Release Volume: 144 Pages: 109-114
  • DOI: DOI:10.1016/j.jconrel.2010.01.023
• [Presentation] Influe nce of glucose-deprivati on cell cycle status and cellular radio resistance under hypoxic conditions (2011)
  • Author(s): Zhao T, Zhu Y, Itasaka S, Ogura M, Y oshimura M, Harada H, Hiraoka M.
  • Organizer: 第13回癌治療増感研究シンポジウム
  • Place of Presentation: 奈良
  • Year and Date: 2011-02-12
• [Presentation] Optical imaging probe for matrix metalloproteinases activity in malignant tumors (2010)
  • Author(s): Zhao T, Harada H, Teramura Y, Tanaka S, Itasaka S, Morinibu A, Shinomiya K, Zhu Y, Hanaoka H, Iwata H, SAji H, Hiraoka M
  • Organizer: 2010 World Molecular Imaging Congress
  • Place of Presentation: 京都
  • Year and Date: 2010-09-09