| Project/Area Number |
16K20070
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Juntendo University |
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Principal Investigator |
OKUBO TAKETO 順天堂大学, 医学部, 助教 (90732884)
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| Research Collaborator |
SUEHARA Yoshiyuki
Saito Tsuyoshi
Hayashi Takuo
Kubota Daisuke
Mukaihara Kenta
Akaike Keisuke
Tanabe Yu
Ishii Midori
Kurihara Taisei
Sano Kei
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 骨巨細胞腫 / Denosumab / バイオマーカー / denosumab / 骨軟部腫瘍 / プロテオミクス / 遺伝子変異解析 |
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| Outline of Final Research Achievements |
Giant cell tumors of bone (GCTB) are locally aggressive osteolytic bone tumors. Some studies have recently reported that denosumab is a novel and effective therapeutic option for GCTB. But, the prediction of treatment effect and the mechanism in GCTB are still unknown. Therefore, we constructed a profiling database of biological characteristics related to the grade of GCTB and the denosumab therapeutic response.
Histologically, the post-denosumab-treated samples were characterized by two lesions: SL-lesion, and FO-lesion. In this study, to clarify the differences in the protein expression between two lesions, we conducted comparative proteomic studies (12 pairs of pre- and post-denosumab treatment samples). We succeeded in constructing a protein expression database related to the fibro-osseous reactions by denosumab treatment. Based on the results, we also succeeded in determining the potential proteins that could be the biomarker for treatment evaluation and prognosis prediction.
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| Academic Significance and Societal Importance of the Research Achievements |
骨巨細胞腫の新規治療薬であるDenosumabの治療反応性に関わる生物学的特徴のタンパク質プロファイリング・データベース構築と治療効果判定や予後予測のバイオマーカー候補となりうるタンパク質同定の成功の報告は世界初であり、今後の骨巨細胞腫の病態理解と治療法開発に道筋を示しうる有力な成果である。
本研究より開発されたバイオマーカーによりDenosumab治療の効果判定や予後予測が可能になるのみならず、データベースより同定されたタンパク質が骨巨細胞腫のさらなる新規治療薬開発に結びつく可能性もあり、骨巨細胞腫患者の治療成績向上に期待ができると考えている。
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