Basic research for development of the DDS system considering tissue and intracellular drug distribution
| 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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Report
(3 results)
Research Products
(18 results)
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[Journal Article] SOCS1 gene therapy has antitumor effects in imatinib-resistant gastrointestinal stromal tumor cells through FAK/PI3K signaling.2018
Author(s)
Sugase T, Takahashi T, Serada S, Fujimoto M, Ohkawara T, Hiramatsu K, Nishida T, Hirota S, Saito Y, Tanaka K, Miyazaki Y, Makino T, Kurokawa Y, Yamasaki M, Nakajima K, Hanasaki K, Kishimoto T, Mori M, Doki Y, Naka T.
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Journal Title
Gastric Cancer.
Volume: epub
Issue: 6
Pages: 968-976
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Downregulation of miR-186 is associated with metastatic recurrence of gastrointestinal stromal tumors.2017
Author(s)
Niinuma T, Kai M, Kitajima H, Yamamoto E, Harada T, Maruyama R, Nobuoka T, Kanda T, Hasegawa T, Tokino T, Sugai T, Shimomura Y, Nakase H, Suzuki H
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Journal Title
Oncology Letters
Volume: 14
Pages: 5703-5710
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinicopathological characteristics, surgery, and survival outcomes of duodenal gastrointestinal stromal tumors.2016
Author(s)
Sugase T, Takahashi T, Nakajima K, Hirota H, Masuzawa T, Nishida T, Kimura Y, Miyazaki Y, Makino T, Kurokawa Y, Yamasaki M, Takiguchi S, Mori M, Doki Y.
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Journal Title
Digestion
Volume: 94
Issue: 11
Pages: 30-36
DOI
Related Report
Peer Reviewed
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[Journal Article] Asian Consensus Guidelines for the Diagnosis and Management of Gastrointestinal Stromal Tumor.2016
Author(s)
Koo DH, Ryu MH, Kim KM, Yang HK, Sawaki A, Hirota S, Zheng J, Zhang B, Tzen CY, Yeh CN, Nishida T, Shen L, Chen LT, Kang YK.
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Journal Title
Cancer Res Treat
Volume: 48
Issue: 4
Pages: 1155-1166
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] 食道非上皮性腫瘍の治療2016
Author(s)
西田俊朗
Organizer
第70回日本食道学会学術集会
Place of Presentation
ザ・プリンス パークタワー東京（東京都港区）
Year and Date
2016-07-05
Related Report
Invited
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