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IPMN as a risk factor for pancreatic ductal adenocarcinoma; challenge for early diagnosis of pancreatic cancer by the assessment of clonal expansion

Research Project

Project/Area Number 20K21633
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research InstitutionKagoshima University

Principal Investigator

Ohtsuka Takao  鹿児島大学, 医歯学域医学系, 教授 (20372766)

Co-Investigator(Kenkyū-buntansha) 山口 浩  東京医科大学, 医学部, 兼任准教授 (20510697)
三森 功士  九州大学, 大学病院, 教授 (50322748)
又木 雄弘  鹿児島大学, 鹿児島大学病院, 特任講師 (10444902)
蔵原 弘  鹿児島大学, 医歯学域医学系, 准教授 (70464469)
Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords膵癌 / IPMN / ゲノム / 予防 / ゲノム医療 / クローン拡大 / 早期診断
Outline of Research at the Start

膵癌の危険因子である膵管内乳頭粘液性腫瘍(IPMN; Intraductal Papillary Mucinous Neoplasm)に注目し、同一膵内に膵癌と膵IPMNが発症する機序を遺伝子解析に基づくクローン拡大(慢性刺激→共通のドライバー遺伝子変異による臓器全体の遺伝子変異と前癌病変の蓄積→別のドライバー遺伝子変異による膵癌とIPMNの選択と拡大)から解明し、膵癌早期診断に有用なバイオマーカーを探索する事を目的とする。本研究は、膵癌発癌過程の機序を一気に解明する学問的意義のみならず、内視鏡で癌の早期診断を得意とする本邦の技術を世界へ向けて発信し社会的意義も有する極めて挑戦的な研究である。

Outline of Final Research Achievements

We found the driver gene mutation namely XXX (unpublished data) which lead sustained benign intraductal papillary mucinous neoplasm (IPMN). The preliminary experiments demonstrated that this mutation was observed only in IPMN having concomitant pancreatic ductal adenocarcinoma (PDAC), but not in IPMN without PDAC. This finding indicates that there possibly exists the clonal expansion in whole pancreatic parenchyma having IPMN with concomitant PDAC.

Academic Significance and Societal Importance of the Research Achievements

危険因子を有する膵癌発癌過程の機序を解明する学問的意義のみならず、膵癌早期診断法の技術を世界へ向けて発信し、広く世界人類の健康に大きく寄与する社会的意義も有する

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (17 results)

All 2022 2021 2020

All Journal Article (13 results) (of which Peer Reviewed: 9 results,  Open Access: 5 results) Presentation (4 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] 特集「診療ガイドライン改訂後の膵炎診療」 慢性膵炎における膵癌スクリーニングはどのように行うべきか2022

    • Author(s)
      保坂優斗、蔵原弘、田上聖徳、大井秀之、伊地知徹也、山崎洋一、川崎洋太、中条哲浩、又木雄弘、大塚隆生
    • Journal Title

      肝胆膵

      Volume: 84 Pages: 375-378

    • Related Report
      2021 Annual Research Report
  • [Journal Article] The novel driver gene ASAP2 is a potential druggable target in pancreatic cancer2021

    • Author(s)
      Fujii A, Masuda T et al
    • Journal Title

      Cancer Sci

      Volume: 112 Issue: 4 Pages: 1655-1668

    • DOI

      10.1111/cas.14858

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bone marrow-derived macrophages converted into cancer-associated fibroblast-like cells promote pancreatic cancer progression2021

    • Author(s)
      Iwamoto Chika、Ohuchida Kenoki、Shinkawa Tomohiko、Okuda Sho、Otsubo Yoshiki、Okumura Takashi、Sagara Akiko、Koikawa Kazuhiro、Ando Yohei、Shindo Koji、Ikenaga Naoki、Nakata Kohei、Moriyama Taiki、Miyasaka Yoshihiro、Ohtsuka Takao、Eto Masatoshi、Akashi Koichi、Nakamura Masafumi
    • Journal Title

      Cancer Letters

      Volume: 512 Pages: 15-27

    • DOI

      10.1016/j.canlet.2021.04.013

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical Utility and Limitation of Diagnostic Ability for Different Degrees of Dysplasia of Intraductal Papillary Mucinous Neoplasms of the Pancreas Using 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography2021

    • Author(s)
      Hozaka Yuto、Kurahara Hiroshi、Oi Hideyuki、Idichi Tetsuya、Yamasaki Yoichi、Kawasaki Yota、Tanoue Kiyonori、Jinguji Megumi、Nakajo Masatoyo、Tani Atsushi、Nakajo Akihiro、Mataki Yuko、Fukukura Yoshihiko、Noguchi Hirotsugu、Higashi Michiyo、Yoshiura Takashi、Tanimoto Akihide、Ohtsuka Takao
    • Journal Title

      Cancers

      Volume: 13 Issue: 18 Pages: 4633-4633

    • DOI

      10.3390/cancers13184633

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 特集「肝胆膵疾患におけるバイオマーカーの意義を探る」 膵癌の膵液miRNA解析とバイオマーカーの意義2021

    • Author(s)
      保坂優斗、蔵原弘、大井秀之、伊地知徹也、米盛圭一、山崎洋一、川﨑洋太、田上聖徳、又木雄弘、大塚隆生
    • Journal Title

      肝胆膵

      Volume: 83 Pages: 659-663

    • Related Report
      2021 Annual Research Report
  • [Journal Article] 特集「胆道・膵管上皮内腫瘍の総整理:診断と治療の現状」 膵管上皮内腫瘍(IPMN, IOPN, ITPN, MCN)に対する外科治療の現状と課題2021

    • Author(s)
      保坂優斗、大塚隆生、大井秀之、平瀬雄規、伊地知徹也、田上聖徳、又木雄弘、蔵原弘
    • Journal Title

      胆と膵

      Volume: 42 Pages: 567-571

    • Related Report
      2021 Annual Research Report
  • [Journal Article] 特集「分枝型IPMNの長期予後と進展様式」 全国多施設共同研究によるIPMN長期予後2021

    • Author(s)
      井手野昇、守田真規子、大塚隆生、中村雅史
    • Journal Title

      肝胆膵

      Volume: 82 Pages: 773-778

    • Related Report
      2021 Annual Research Report
  • [Journal Article] 特集「グローバルな視点からみた膵疾患update」 IPMN国際診療ガイドライン-次期改訂に向けて-2021

    • Author(s)
      大塚隆生、田中雅夫
    • Journal Title

      膵臓

      Volume: 36 Pages: 238-244

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FoundationOne CDx gene profiling in Japanese pancreatic ductal adenocarcinoma patients: a single-institution experience2020

    • Author(s)
      Kimura R, Ohtsuka T, Kubo M, Kajihara A, Fujii A, Watanabe Y, Mori Y, Ikenaga N, Nakata K, Shindo K, Ohuchida K,Nakamura M
    • Journal Title

      Surgery Today

      Volume: 51 Issue: 4 Pages: 619-626

    • DOI

      10.1007/s00595-020-02123-2

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Early detection of pancreatic cancer: role of biomarkers in pancreatic fluid samples.2020

    • Author(s)
      Ideno N, Mori Y, Nakamura M, Ohtsuka T.
    • Journal Title

      Diagnostics

      Volume: 10 Issue: 12 Pages: 1056-1056

    • DOI

      10.3390/diagnostics10121056

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Remnant pancreatic cancer after pancreatic resection for early-stage pancreatic cancer: Is it more frequent compared to advanced-stage cancer?2020

    • Author(s)
      Miyasaka Y, Ohtsuka T, Kimura R, Matsuda R, Mori Y, Nakata K, Watanabe M, Oda Y, Nakamura M.
    • Journal Title

      Annals of Gastroenterological Surgery.

      Volume: 4 Issue: 4 Pages: 448-454

    • DOI

      10.1002/ags3.12340

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Concomitant intraductal papillary mucinous neoplasm in pancreatic ductal adenocarcinoma is an independent predictive factor for the occurrence of new cancer in the remnant pancreas.2020

    • Author(s)
      Matsuda R, Miyasaka Y, Ohishi Y, Yamamoto T, Saeki K, Mochidome N, Abe A, Ozono K, Shindo K, Ohtsuka T, Kanetake C, Nakamura M, Oda Y.
    • Journal Title

      Annals of Surgery

      Volume: 271 Issue: 5 Pages: 941-948

    • DOI

      10.1097/sla.0000000000003060

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] High-risk lesions in the remnant pancreas: fate of the remnant pancreas after pancreatic resection for pancreatic cancer and intraductal papillary mucinous neoplasms.2020

    • Author(s)
      Miyasaka Y, Ohtsuka T, Matsuda R, Mori Y, Nakata K, Ohuchida K, Nakamura M.
    • Journal Title

      Surgery Today

      Volume: 50 Issue: 8 Pages: 832-840

    • DOI

      10.1007/s00595-019-01852-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] Guidelines for the management of IPMN of the pancreas2021

    • Author(s)
      Ohtsuka T
    • Organizer
      第33回日本肝胆膵外科学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 「慢性膵炎診療ガイドライン2021改訂の要点と課題」 慢性膵炎の予後2021

    • Author(s)
      大塚隆生
    • Organizer
      第53回日本膵臓学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Multifocal lesions in IPMNs; Intraoperative pancreatic juice cytology.2021

    • Author(s)
      Ohtsuka T
    • Organizer
      BP Surgical Wekk in Korea 2021(招待講演)(国際学会)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] IPMN; Surveillance? Surgery? Search for the scientific truth?2020

    • Author(s)
      Ohtsuka T
    • Organizer
      2nd PAHPBS International Symposium.(招待講演)(国際学会)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2020-08-03   Modified: 2023-01-30  

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