| Project/Area Number |
18H02630
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | Kobe University |
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Principal Investigator |
Zen Yoh 神戸大学, 医学研究科, 医学研究員 (90377416)
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| Co-Investigator(Kenkyū-buntansha) |
小松 正人 神戸大学, 医学部附属病院, 助教 (50531753)
藤倉 航平 神戸大学, 医学研究科, 医学研究員 (50773751)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
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| Keywords | 胆管癌 / 前癌病変 / 自己免疫性膵炎 / IgG4 / エクソーム / プロテオーム / プロテオーム解析 / リン酸化 / IPNB / 硬化性胆管炎 / Exome / Proteome / Exome解析 / 胆管内乳頭状腫瘍 / 胆管内管状腫瘍 / 粘液性嚢胞腫瘍 / Repertoire / エクソーム解析 / 胆嚢内乳頭状腫瘍 / APC / CTNNB1 / STK11 |
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| Outline of Final Research Achievements |
Global gene analysis of intraductal papillary neoplasm of the bile duct (IPNB) and intracholecystic papillary neoplasm (ICPN) identified recurrent mutations in APC, CTNNB1 and STK11. Intraductal tubulopapillary neoplasm of the bile duct (biliary ITPN) had mutations in CTNNB1, SF3B1, BAP1 and BRCA1. Those neoplasms shared activated pathways with cholangiocarcinomas, but the degrees of activation in pathways appeared to differ between those neoplasms and cholangiocarcinoma. The repertoire analysis in non-neoplastic disorders including IgG4-related disease indicated a polyclonal pattern of lymphocyte induction. According to phosphoproteomic data, signaling pathways related to B-cells or immunoglobulins were significantly activated in IgG4-related disease.
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| Academic Significance and Societal Importance of the Research Achievements |
希少疾患は頻度が低いため研究対象とするのが困難である．そのため，その病態解析は進まず，診断，治療法の進歩が遅れることが問題とされてきた．本研究では，胆膵領域の希少疾患を対象に最新の技術を用いた研究を行い，腫瘍性疾患では特徴的な遺伝子異常や，活性化している分子経路が明らかとなった．非腫瘍性疾患でも活性化している分子経路が明らかとなり，今後の診断や治療に関連したより臨床的な研究につながる結果が得られた．
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