| Project/Area Number |
20249060
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Hokkaido University |
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Principal Investigator |
OZAKI Michitaka 北海道大学, 大学院・医学研究科, 特任教授 (80256510)
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| 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)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥49,010,000 (Direct Cost: ¥37,700,000、Indirect Cost: ¥11,310,000)
Fiscal Year 2010: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2009: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Fiscal Year 2008: ¥24,830,000 (Direct Cost: ¥19,100,000、Indirect Cost: ¥5,730,000)
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| 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 / 分子機能 / 抗体診断・治療 / ライブ診断 / 発光イメージング / 光プローブ / ストレスイメージング / カスパーゼ / トランスジェニックマウス / 肝腫瘍 / 抗体診断 / Dlk-1 |
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| 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.
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