2020 Fiscal Year Final Research Report
Real-time and non-invasive imaging of tumor cell death and its application to radiation treatment
| Project/Area Number |
18K07768
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52040:Radiological sciences-related
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| Research Institution | Kitasato University |
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Principal Investigator |
Kagiya Go 北里大学, 医療衛生学部, 准教授 (30524243)
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| Co-Investigator(Kenkyū-buntansha) |
小川 良平 富山大学, 学術研究部医学系, 准教授 (60334736)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 細胞死 / ネクローシス / プロテインスプライシング / リアルタイムイメージング / 放射線治療 |
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| Outline of Final Research Achievements |
Necrosis, a form of cell death, not only occurs with the development of various diseases but also with a tumor tissue response to cancer treatment. Therefore, pursuing the progress for cancer therapy through induction of necrosis may be one of the most effective approaches for cancer eradication. We herein describe the development of a real-time imaging system to visualize intratumoral necrosis. The system is composed of two types of cells expressing either one of two necrosis imaging reporters that consist of two split-luciferase fragments. When necrosis occurs in a tumor composed of both of the cells, the two types of leaked reporters can reconstitute the enzymatic activity as a result of protein trans-splicing, and thereby emit bioluminescence. This system allowed in vitro imaging of necrosis. We further confirmed real-time imaging of intratumoral necrosis caused by physical or chemical tissue disruption, validating its application in in vivo necrosis imaging.
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| Free Research Field |
放射線生物学
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| Academic Significance and Societal Importance of the Research Achievements |
腫瘍内で誘発される細胞死（アポトーシス，ネクローシス）を低侵襲かつリアルタイムに可視化するシステムは，腫瘍内細胞死の動態解析を簡便にし，放射線治療条件の最適化および抗がん剤を併用した放射線化学療法の開発等，治療への応用に有用な手段となる。これまで我々は,放射線や抗がん剤治療に対し抵抗性である腫瘍内低酸素細胞のアポトーシスを可視化するシステム構築に成功している。本研究課題では，もう一つの細胞死，ネクローシスを可視化するシステム構築を目的とした。その結果, 腫瘍内で誘発されるネクローシスの低侵襲かつリアルタイム可視化に成功した。今後は構築した細胞死可視化システムを用い，がん治療への還元を目指す。
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