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2010 Fiscal Year Final Research Report

Development of comprehensive methods for diagnosis/therapy by optic bio-imaging

Research Project

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Project/Area Number 20249060
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionHokkaido University

Principal Investigator

OZAKI Michitaka  北海道大学, 大学院・医学研究科, 特任教授 (80256510)

Co-Investigator(Kenkyū-buntansha) OZAWA Takeaki  東京大学, 理学研究科, 教授 (40302806)
MORITA Naoki  産業技術総合研究所, 分子生物工学研究グループ, 研究グループ長 (60371085)
Project Period (FY) 2008 – 2010
Keywords生体イメージング / 光イメージング / 発光 / caspase-3 / アポトーシス
Research Abstract

In the present study, we performed two major experiments.
Theme A) Development of bio-imaging method for qualitative/quantitative evaluation of tumors and drug sensitivity : luciferase-based new optic prove for in vivo molecular function. We developed optic probe for caspase-3 activity and adenovirus vector encoding for the probe. By using this, we performed cellular and mice experiments, successfully showing apoptosis in the tissue. Especially, in hypoxia/reoxygenation (ischemia/reperfusion) and post-hepatectomy liver regeneration, we succeeded in imaging the dynamism of oxidative stress-induced apoptotic liver injury.
Theme B) Development of a new diagnostic/therapeutic method for tumor detection and characterization by the newly developed optic probe (in vivo/ex vivo imaging). We mounted the optic probe to various antibodies including Dlk-1/CEA/EMA/Ep-CAM. Also, we checked expressions of Dlk-1/CEA/EMA/Ep-CAM in various cell lines by FACS/Western Blot, and performed subcutaneous tumor cell implantation in nu/nu mice. In the experiments using hepatoma cell line (Huh-7) expressing Dlk-1, we proved the efficacy of our new optic probe in vivo. We measured enough signals from implanted liver tumor as well as subcutaneous tumor in mice without UV exposure. We are now challenging other antibodies to ensure clinical relevance.

  • Research Products

    (41 results)

All 2012 2011 2010 2009 2008 Other

All Journal Article (15 results) (of which Peer Reviewed: 13 results) Presentation (24 results) Book (1 results) Remarks (1 results)

  • [Journal Article] 生体イメージング法による細胞・臓器のリアルタイム評価法の開発(Development of the innovative in vivo imaging technique for cell/organ functions)2012

    • Author(s)
      芳賀早苗、尾崎倫孝
    • Journal Title

      Organ Biology

      Volume: vol.19 No.1(掲載予定)

  • [Journal Article] In vivo monitoring of liver damage by caspase-3 probe2012

    • Author(s)
      Michitaka Ozaki, Sanae Haga, Takeaki Ozawa
    • Journal Title

      Theranostics

      Volume: 2(2) Pages: 207-14

    • Peer Reviewed
  • [Journal Article] 移植臓器の非侵襲的モニタリング法の開発2011

    • Author(s)
      尾崎倫孝、芳賀早苗、森田直樹、深井原、藤堂省、小澤岳昌、近江谷克裕
    • Journal Title

      Organ Biology18

      Pages: 134-140

    • Peer Reviewed
  • [Journal Article] 移植臓器の非侵襲的モニタリング法の開発2011

    • Author(s)
      尾崎倫孝、芳賀早苗、森田直樹、深井原、藤堂省、小澤岳昌、近江谷克祐
    • Journal Title

      Organ Biology 18(1)

      Pages: 134-140

    • Peer Reviewed
  • [Journal Article] Inhibition of nuclear factor-kappa B (NF-κB)suppresses peritoneal dissemination of gastric cancer by blocking cancer cell adhesion2010

    • Author(s)
      Mino K, Ozaki M, Nakanishi K, Haga S, Sato M, Kina M, Takahashi M, Takahashi N, Kataoka A, Yanagihara K, Ochiya T, Kamiyama T, Umezawa K, Todo S
    • Journal Title

      Cancer Sci

      Volume: 102(5) Pages: 1052-1058

    • Peer Reviewed
  • [Journal Article] p66Shc plays a pivotal role in impaired liver regeneration in aged mice by a redox-dependent mechanism2010

    • Author(s)
      Sanae Haga, Naoki Morita, Kaikobad Irani, Masato Fujiyoshi, Tetsuya Ogino, Michitaka Ozaki
    • Journal Title

      Laboratory Investigation

      Volume: 90 Pages: 1718-1726

    • Peer Reviewed
  • [Journal Article] In vivo far-red luminescence imaging of a biomarker based on BRET from Cypridina bioluminescence to an organic dye2009

    • Author(s)
      Chun Wu, Kazuhiro Mino, Hidetoshi Akimoto, Makiko Kawabata, KojiNakamura, Michitaka Ozaki, Yoshihiro Ohmiya
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America

      Volume: 106(37) Pages: 15599-15603

    • Peer Reviewed
  • [Journal Article] Hepatic Ischemia Induced Immediate Oxidative Stress after Reperfusion and Determined the Severity of the Reperfusion-induced Damage2009

    • Author(s)
      Sanae Haga, S. James Remington, Naoki Morita, Keita Terui, and Michitaka Ozaki
    • Journal Title

      Antioxidants & Redox Signaling

      Volume: 11 Pages: 2563-2572

    • Peer Reviewed
  • [Journal Article] Activation of c-Jun N-terminal kinase is essential for oxidative stress-induced Jurkat cell apoptosis by monochloramine2009

    • Author(s)
      Ogino T, Ozaki M, Hosako M, Omori M, Okada S, Matsukawa A
    • Journal Title

      Leukemia Research

      Volume: 33(1) Pages: 151-158

    • Peer Reviewed
  • [Journal Article] In vivo bioluminescence imaging of bone marrow-derived cells in brain inflammation2009

    • Author(s)
      Hidetoshi Akimoto, Hyuck Joon Kwon, Michitaka Ozaki, Kazunori Yasuda, Ken-ichi Honma, Yoshihiro Ohmiya
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 380 Pages: 844-849

    • Peer Reviewed
  • [Journal Article] The survival pathwaysphosphatidylinositol-3 kinase(PI3-K)/phosphoinositide-dependent protein kinase 1 (PDK1)/Akt modulate liver regeneration through hepatocyte size rather than proliferation2009

    • Author(s)
      Sanae Haga, Michitaka Ozaki, HiroshiInoue, Yasuo Okamoto, Wataru Ogawa, Kiyoshi Takeda, Shizuo Akira, Satoru Todo
    • Journal Title

      Hepatology

      Volume: 49 Pages: 204-214

    • Peer Reviewed
  • [Journal Article] 光る生物の応用研究最前線-光イメージングでストレスを診る2009

    • Author(s)
      尾崎倫孝
    • Journal Title

      ビオフィリア

      Volume: Vol.5 No.4

    • Peer Reviewed
  • [Journal Article] Preventing hypoxia/reoxygenation damage to hepatocytes by p66SHC ablation : up-regulation of anti-oxidant and anti-apoptotic proteins2008

    • Author(s)
      Sanae Haga, Keita Terui, Moto Fukai, YukoOikawa, Kaikobad Irani, Hiroyuki Furukawa, Satoru Todo, Michitaka Ozaki.
    • Journal Title

      Journal of Hepatology

      Volume: 48 Pages: 422-432

    • Peer Reviewed
  • [Journal Article] 細胞・臓器機能の生体イメージング2008

    • Author(s)
      芳賀早苗、尾崎倫孝
    • Journal Title

      Organ Biology

      Volume: 15(4) Pages: 369-376

    • Peer Reviewed
  • [Journal Article] Rapid Methods of Detecting the Target Molecule in immunohistology using a Bioluminescence Probe

    • Author(s)
      Chun Wu, Ke-Yong Wang, Xin Guo, Masanori Sato, Michitaka Ozaki, Shyohei Shimajiri, Yoshihiro Ohmiya, Yasuyuki Sasaguri
    • Journal Title

      Luminescence : The Journal of Biological and Chemical Luminescence

      Volume: (in press)

  • [Presentation] Molecular analysis of liver regeneration in mouse : roles of cell proliferation and growth2011

    • Author(s)
      MichitakaOzaki, SanaeHaga, HiroshiInoue, Wataru Ogawa
    • Organizer
      MBSJ2011第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      20111213-16
  • [Presentation] Analysis of different cellular responses of cells in hyperglycemic condition or steatotic hepatocytes- a simulated study of stress response in metabolic syndrome2011

    • Author(s)
      Sanae Haga, Takeaki Ozawa, Takako Aoyama, Naoki Morita, S.James Remington, RiichiroAbe, Michitaka Ozaki
    • Organizer
      MBSJ2011第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      20111213-16
  • [Presentation] 生体イメージング法による細胞・臓器のリアルタイム評価法の開発2011

    • Author(s)
      尾崎倫孝
    • Organizer
      第38回日本臓器保存生物医学会学術集会
    • Place of Presentation
      江陽グランドホテル(仙台)
    • Year and Date
      20111125-26
  • [Presentation] Age-associated p66Shcinduced redox-dependent liver damage and impaired regeneration after hepatectomy in aged mice2011

    • Author(s)
      Michitaka Ozaki, Sanae Haga, KaikobadIrani, NaokiMorita, Yoshimi Kaneshima, Takeaki Ozawa
    • Organizer
      62th Annual meeting of AASLD
    • Place of Presentation
      Moscone West Convention Center, San Francisco, USA
    • Year and Date
      20111104-08
  • [Presentation] 脂肪肝におけるFas過剰発現および細胞内酸化的ストレスによる肝再生不全の検討2011

    • Author(s)
      芳賀早苗,森田直樹,青山貴子,小澤岳昌,Remington S. James,阿部理一郎,尾崎倫孝
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      20110921-24
  • [Presentation] Bio-imaging of Surgical Stresses-Dynamic Analyses of Liver Oxidative Stress and Damage2011

    • Author(s)
      M. Ozaki, S. Haga, T. Ozawa, N. Morita, Y.Kaneshima, J. Remington
    • Organizer
      5^<TH> European Conference of the International Federation for Medical and Biological Engineering Bdapest Congress & World Trade Center
    • Place of Presentation
      Bdapest, Hungary
    • Year and Date
      20110914-18
  • [Presentation] Collagen Vitrigel Sheet as a Novel Drug Delivery Bio-material2011

    • Author(s)
      Sanae Haga, Toshiaki Takezawa,TakeakiOzawa,James Remington, Naoki Morita andMichitaka Ozaki
    • Organizer
      5^<TH> European Conference of the International Federation for Medical and Biological Engineering Budapest Congress & World Trade Center
    • Place of Presentation
      Budapest, Hungary
    • Year and Date
      20110914-18
  • [Presentation] 脂肪肝における肝再生不全機序の解析2011

    • Author(s)
      芳賀早苗、森田直樹、小澤岳昌、レミントンジェームズ、尾崎倫孝
    • Organizer
      第18回肝細胞研究会
    • Place of Presentation
      東京ガーデンパレス
    • Year and Date
      20110624-25
  • [Presentation] 種々の病態における肝再生の分子制御機構の解析(細胞増殖・細胞成長・細胞死の観点から)2011

    • Author(s)
      尾崎倫孝、芳賀早苗、森田直樹、金島由実、James Remington、小澤岳昌、井上啓、松本道宏
    • Organizer
      第18回肝細胞研究会
    • Place of Presentation
      東京ガーデンパレス
    • Year and Date
      20110624-25
  • [Presentation] 外科治療による肝細胞ストレスと障害・再生への影響(生体イメージング法をもちいた動的解析)2011

    • Author(s)
      尾崎倫孝、芳賀早苗、森田直樹、青山貴子、金島由実、Kaikobad Irani、James Remington
    • Organizer
      第18回細胞研究会
    • Place of Presentation
      東京ガーデンパレス
    • Year and Date
      20110624-25
  • [Presentation] Oxidative stress-mediated liver damage and impaired liver regeneration in partial hepatectomy model of fatty mouse2010

    • Author(s)
      Sanae Haga, Naoki Morita, Takeaki Ozawa,Remington S. James, Michitaka Ozaki
    • Organizer
      BMB2010(第33回日本分子生物学会年会・第83回日本生化学会大会合同大会)
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      20101207-10
  • [Presentation] 重水を付加した新規保存液と光プローブによる臓器・細胞評価・治療法の開発2010

    • Author(s)
      尾崎倫孝
    • Organizer
      第37回日本臓器保存生物医学会学術集会
    • Place of Presentation
      新潟グランドホテル
    • Year and Date
      2010-11-20
  • [Presentation] A novel NF-κB inhibitor DHMEQ sensitized pancreatic cancer cells to gemcitabine treatment in vitro and in a mouse model2010

    • Author(s)
      佐藤正法、尾崎倫孝、中西一彰、渡邉俊之、永生高広、馬場基、藤好真人、芳賀早苗、三野和宏、梅澤一夫、近江谷克裕、神山俊哉、藤堂省
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2010-09-22
  • [Presentation] Hepatic ischemia induced immediate oxidative stress after reperfusion and determined the severity of the reperfusion-induced damage. in vivo dynamic analysis of liver oxidative stress and damage2009

    • Author(s)
      Sanae Haga, S. James Remington, Takeaki Ozawa, Naoki Morita, Keita Terui, Michitaka Ozaki
    • Organizer
      60th Annual meeting of AASLD
    • Place of Presentation
      Boston, USA
    • Year and Date
      20091030-1103
  • [Presentation] A novel NF-κB in hibitor DHMEQ suppressed peritoneal dissemination of pancreatic cancer in mouse xenograftmodel2009

    • Author(s)
      Masanori Sato, M. Ozaki, K. Nakanishi, T.Watanabe, S. Haga, K. Mino, H. Yokoo, K.Umezawa, Y. Ohmiya, T. Kamiyama, S.Todo
    • Organizer
      ECCO 15/ESMO 34Multidisciplinary Congress
    • Place of Presentation
      Berlin
    • Year and Date
      20090920-24
  • [Presentation] A novel NF-κB inhibitor DHMEQ could suppress peritoneal dissemination of gastric cancer by anti-tumor/-adhesive effects in mice2009

    • Author(s)
      Kazuhiro Mino, Kazuaki Nakanishi, SanaeHaga, Masanori Sato, Masaya Kina, HidekiYokoo, Toshiya Kamiyama, KazuoUmezawa, Michitaka Ozaki, Satoru Todo
    • Organizer
      ECCO 15/ESMO 34Multidisciplinary Congress
    • Place of Presentation
      Berlin
    • Year and Date
      20090920-24
  • [Presentation] #1 molecular mechanism of liver injury, protection and regeneration, #2 bio-imaging of molecular functions and tumor by opticprobes2009

    • Author(s)
      Michitaka Ozaki
    • Organizer
      Japan-Denmark Joint Workshop on Molecular Cancer Research
    • Place of Presentation
      Tokyo
    • Year and Date
      20090119-20
  • [Presentation] Dynamic analysis of surgical liver stress with newly developed optical probes2009

    • Author(s)
      芳賀早苗,小澤岳昌,S. James Remington,森田直樹,尾崎倫孝
    • Organizer
      第32回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-12-11
  • [Presentation] Bio-imagimg of Surgical Stress dynamic analysis of liver oxidative stress and damage2009

    • Author(s)
      Michitaka Ozaki, Sanae Haga, Takeaki Ozawa, S. James Remington, NaokiMorita, Yoshihiro Ohmiya
    • Organizer
      Molecular Imaging for Systems Biology Okazaki
    • Year and Date
      2009-11-06
  • [Presentation] PI3-K/PDK1/Akt pathway is crucial in liver regeneration through hepatocyte cell growth2009

    • Author(s)
      Sanae Haga, Hiroshi Inoue, Yasuo Okamoto, Wataru Ogawa, Keita Terui, MichitakaOzaki
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2009-10-22
  • [Presentation] 光プローブをもちいた虚血/再灌流時肝酸化ストレスと傷害の生体イメージング2008

    • Author(s)
      芳賀早苗、小澤岳昌、James Remington、森田直樹、藤堂省、尾崎倫孝
    • Organizer
      BMB2008
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      20081209-12
  • [Presentation] 虚血・再灌流障害抑制:最近のトピックス2008

    • Author(s)
      尾崎倫孝、芳賀早苗、及川優子、岩垣博己、深井原、藤堂省、小川渉、井上啓、小澤岳昌
    • Organizer
      第35回日本臓器保存生物医学会総会
    • Place of Presentation
      六本木アカデミーヒルズ
    • Year and Date
      20081123-24
  • [Presentation] 生体光イメージング法による臓器移植の新たな展開-分子機能イメージングによるグラフト機能評価・予後予測の可能性2008

    • Author(s)
      尾崎倫孝、芳賀早苗、及川優子、三野和宏、森田直樹、藤堂省、近江谷克裕、小澤岳昌、James Remington
    • Organizer
      第35回日本臓器保存生物医学会総会
    • Place of Presentation
      六本木アカデミーヒルズ
    • Year and Date
      20081123-24
  • [Presentation] Non-invasive real time monitoring of oxidative stress and damage by newly developed optical probes in mouse liver ischemia/reperfusion2008

    • Author(s)
      Michitaka Ozaki, Sanae Haga, S.James Remington, Takeaki Ozawa, Yuko Oikawa, Satoru Todo.
    • Organizer
      AASLD annual meeting
    • Place of Presentation
      San Fransisco
    • Year and Date
      20081101-04
  • [Book] 移植のための臓器摘出と保存2012

    • Author(s)
      深井原、尾崎倫孝
    • Total Pages
      11-20
    • Publisher
      シュプリンガー・ジャパン
  • [Remarks] サイエンスZERO「生体の機能を照らし出せ~光イメージング~」(NHK教育)2009.2.15

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Published: 2013-07-31  

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