Photodynamic diagnosis of malignant brain tumor: analysis of molecular mechanisms and application to clinical diagnosis
| Project/Area Number |
23650619
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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 |
Tumor diagnosis
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
ISHIKAWA Toshihisa 独立行政法人理化学研究所, ライフサイエンス技術基盤研究センター, 上級研究員 (60193281)
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| Co-Investigator(Kenkyū-buntansha) |
KUROIWA Toshihiko 大阪医科大学, 医学部, 教授 (30178115)
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| Co-Investigator(Renkei-kenkyūsha) |
OGURA Shun-ichiro 東京工業大学, フロンティア研究機構, 特任准教授 (90343160)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 悪性脳腫瘍 / 光線力学診断 / 光線力学治療 / 5-アミノレブリン酸(ALA) / ポルフィリン / ABCG2 / Nrf2 / 5-アミノレブリン酸( ALA) / 癌幹細胞 / 脳腫瘍 / トランスポーター / アミノレブリン酸 / メタボローム解析 / 遺伝子発現 / 代謝 / 光線力学診断法 / 転写制御 / バイオマーカー / 臨床応用 |
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| Research Abstract |
Fluorescence-guided gross-total resection has recently been developed, where 5-aminolevulinic acid (ALA) is administered as the precursor of protoporphyrin IX (PpIX). This study has been undertaken to gain insight into the molecular mechanism underlying ALA-induced PpIX accumulation in malignant brain tumors. By comparing gene expression profiles, PpIX accumulation in brain tumor was found to be regulated by two transporters PEPT and ABCG2 that transport ALA and PpIX, respectively. Transcription factor Nrf2 plays a significant role in regulating ABCG2 gene expression, where one SNP (-617C>A) in the Nrf2 gene is suggested to be critically involved. We therefore developed a rapid and simple method to detect that SNP allele. Furthermore, we identified one drug that is potent for ABCG2-inhibition and may significantly enhance the efficacy of ALA-based photodynamic diagnosis and therapy.
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Report
(4 results)
Research Products
(71 results)
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[Journal Article] Pivotal roles of peptide transporter PEPT1 and ATP-binding cassette (ABC) transporter ABCG2 in 5-aminolevulinic acid (ALA)-based photocytotoxicity of gastric cancer cells in vitro2012
Author(s)
Hagiya Y, Endo Y, Yonemura Y, Takahashi K, Ishizuka M, Abe F, Tanaka T, Okura I, Nakajima M, Ishikawa T, Ogura S
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Journal Title
Photodiagnosis Photodyn Ther
Volume: 9(3)
Issue: 3
Pages: 204-214
DOI
Related Report
Peer Reviewed
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[Presentation] 悪性脳腫瘍の光線力学診断と治療をめざしたABCG2 阻害剤のデザイン2013
Author(s)
井上裕貴, 池上洋二, 佐野和美, 小金井美穂, 吉田久博, 藤城高広, 木村誠吾, 深見竹広, 梶本宜永, 宮武伸一, 黒岩敏彦, 石川智久
Organizer
ポルフィリンALA 学会
Place of Presentation
横浜
Year and Date
2013-04-27
Related Report
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[Presentation] Transporter-mediated drug interaction strategy for ALA-based photodynamic diagnosis of malignant brain tumor : molecular design of ABCG2 inhibitors2012
Author(s)
Takahashi, K., Ikeda, N., Kajimoto, Y., Hagiya, Y., Ogura, S., Miyatake, S., Kuroiwa, T., Ishikawa, T
Organizer
International Forum "Patients and Medicines"
Place of Presentation
横浜
Year and Date
2012-11-16
Related Report
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[Presentation] Transporter-mediated drug interaction strategy for ALA-based photodynamic diagnosis of malignant brain tumor: molecular design of ABCG2 inhibitors2012
Author(s)
Takahashi, K., Ikeda, N., Kajimoto, Y., Hagiya, Y., Ogura, S., Miyatake, S., Kuroiwa, T., Ishikawa, T.
Organizer
International Forum “Patients and Medicines"
Place of Presentation
理化学研究所（横浜）
Related Report
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[Presentation] Molecular fluorescence imaging to assist neurosurgery of malignant brain tumors in humans : from bench to bedside2011
Author(s)
Ishikawa, T., Takahashi, K., Ikeda, N., Kajimoto, Y., Hagiya, Y., Ogura, S., Miyatake, S., Kuroiwa, T
Organizer
第70回日本癌学会学術総会
Place of Presentation
名古屋
Year and Date
2011-10-03
Related Report
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[Presentation] Molecular fluorescence imaging to assist neurosurgery of malignant brain tumors in humans: from bench to bedside2011
Author(s)
Ishikawa, T., Takahashi, K., Ikeda, N., Kajimoto, Y., Hagiya, Y., Ogura, S., Miyatake, S., Kuroiwa, T.
Organizer
13th Japanese-German Cancer Workshop(招待講演)
Place of Presentation
グランドプリンスホテル広島（広島）
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