Identification of blood biomarkers predicting clinical efficacy of molecular targeting agents in multiple myeloma
Project/Area Number |
16K09855
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
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Research Institution | Nagoya City University |
Principal Investigator |
Iida Shinsuke 名古屋市立大学, 医薬学総合研究院(医学), 教授 (50295614)
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Co-Investigator(Kenkyū-buntansha) |
桶本 和男 名古屋市立大学, 大学院薬学研究科, 助教 (50415486)
前川 京子 同志社女子大学, 薬学部, 教授 (70270626)
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Project Period (FY) |
2016-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 多発性骨髄腫 / 分子標的薬 / バイオマーカー / マイクロRNA / セルフリーDNA / 脂質 / 血液 / 病態進展 / 血液中バイオマーカー / cell free DNA / 脂質メタボロミクス / ボルテゾミブ / 臨床効果 / 末梢神経障害 / リキッドバイオプシー / microRNA / 脂質メタボローム / 効果予測 / miRNA / 脂質メタボローム解析 / エキソソーム / 遊離核酸 / 医療 / トランスレーショナルリサーチ / 骨髄腫 |
Outline of Final Research Achievements |
The purpose of this study is to explore predictive or prognostic biomarkers in blood in patients with multiple myeloma (MM). Cell free nuclear acids such as microRNA and cfDNA isolated from peripheral blood were analyzed by next generation sequencing in association with clinical information including patients’ prognosis and sensitivity to molecular targeting agents. Our study identified several serum microRNAs associated with sensitivity to bortezomib therapy. Sequential genetic analysis of cfDNAs in the same patients could identify some specific mutations relevant to the disease progression in MM. As well, serum lipid metabolites were comprehensively analyzed. It identified some lipid metabolites which might predict poor response to bortezomib plus dexamethasone therapy and occurrence of grade 2 or higher bortezomib-induced peripheral neuropathy. Further studies are needed to validate such candidate biomarkers in prospective large-scale studies.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、採取が簡便で臨床応用しやすい血液サンプルから診断マーカーとして血清中の遊離核酸と脂質代謝物を検討した点が特色である。これまでの造血器腫瘍、特に多発性骨髄腫領域では、その測定系や評価法は十分に確立されていない。本研究により、リキッドバイオプシーの臨床応用に向けた新たな基盤を形成できたと考えている。
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Report
(5 results)
Research Products
(10 results)
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[Journal Article] Low expression of neural adhesion molecule, CD56, is associated with poor efficacy of bortezomib plus dexamethasone therapy in multiple myeloma.2018
Author(s)
Yoshida T, Ri M, Kinoshita S, Narita T, Totani H, Ashour R, Ito A, Kusumoto S, Ishida T, Komatsu H, Iida S
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Journal Title
PLos One
Volume: 13
Issue: 5
Pages: e0196780-e0196780
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] 1.Lipidomic profiling of plasma samples in patients with newly diagnosed multiple myeloma; a biomarker study for predicting the response and toxicity of Melphalan, Prednisolone, and Bortezomib (MPB) regimen: an ancillary study of JCOG1105 (JCOG1105A1)2019
Author(s)
Masaki Ri, Shinsuke Iida, Dai Maruyama, Kosuke Saito, Yoshiro Saito, Satoshi Osaga, Masahiro Tohkin, Naoki Miyata, Noriko Fukuhara, Kana Miyazaki, Norifumi Tsukamoto, Hideki Tsujimura, Makoto Yoshimitsu, Kenichi Miyamoto, Kunihiro Tsukasaki, and Hirokazu Nagai
Organizer
61st. Annual Meeting of American Society of Hematology
Related Report
Int'l Joint Research
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[Presentation] Comprehensive genetic analysis of multiple myeloma in Japan2019
Author(s)
Kanamori T, Sanada M, Ri M, Ueno H, Nishijima D, Yasuda T, Aoki S, Asano A, Tachita T, Kinoshita S, Narita T, Ito A, Kusumoto S, Masuda Y, Kobayashi N, Shiozawa Y, Yoshida K, Nakagawa M, Nannya Y, Shiraishi Y, Chiba K, Tanaka H, Komatsu H, Miyano S, Handa H, Ogawa S, Iida S
Organizer
24th. Congress of European Hematology Association
Related Report
Int'l Joint Research
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[Presentation] Analysis of expression levels, mutations, and methylation status of CRBN-related genes pre- and post-lenalidomide treatment in multiple myeloma2019
Author(s)
Tachita T, Kinoshita S, Ri M, Aoki S, Asano A, Kanamori T, Totani H, Asao Y, Narita T, Ito A, Kusumoto S, Komatsu H, Iida S
Organizer
24th. Congress of European Hematology Association
Related Report
Int'l Joint Research
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[Presentation] Identification of circulating serum microRNAs as novel biomarkers predicting disease progression and sensitivity to bortezomib treatment in multiple myeloma.2016
Author(s)
Narita T, Ri M, Kinoshita S, Yoshida T, Totani H, Ashour R, Masaki A, Ito A, Kusumoto S, Ishida T, Komatsu H, Osabe M, Tohkin M, Iida S
Organizer
58th Annual Meeting of American Society of Hematology
Place of Presentation
San Diego, (USA)
Related Report
Int'l Joint Research