| Project/Area Number |
16K15600
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
General surgery
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
NISHIDA TOSHIROU 国立研究開発法人国立がん研究センター, 中央病院, 病院長 (40263264)
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| Co-Investigator(Kenkyū-buntansha) |
安永 正浩 国立研究開発法人国立がん研究センター, 先端医療開発センター, ユニット長 (80450576)
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| Research Collaborator |
KUROKAWA Kazuo 理化学研究所, 光量子工学研究領域 (40333504)
MANABE Shino 理化学研究所, 伊藤細胞制御化学研究室 (60300901)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | Drug-Delivery System / 分子標的治療薬 / イマチニブ / 消化管間質腫瘍 / 細胞株 / DDS / 薬物動態 / 薬剤動態 |
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| Outline of Final Research Achievements |
It is important to develop DDS which efficiently and specifically delivers anti-cancer agents to cancer cells. The purpose of this research is to develop basic technology to measure accurately drug distribution at cellular and organellar levels using GIST-imatinib as a model. We have studied using xenograft model and GIST cell lines. Imatinib distribution in tumor tissues was measured with mass-microscopes whose sensitivity was enhanced nearly 10-hold.
Although tumor vascular density greatly decreased after imatinib therapy, there was no change in tumor tissue distribution of imatinib in xenograft models. Intracellular imatinib distribution was measured by fluorescent-tagged imatinib, Turn-ON method, and using anti-imatinib antibody. When imatinib entered into tumor cells, it rapidly accumulated mainly in the secondary lysosome, and partly distributed ER-like structures. Taken together, imatinib was accumulated mainly in lysosome and partly in ER-like structures of tumor cells.
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