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Mathematical analysis of the mechanism of cancer initiation with the aging of stem cells

Planned Research

Project AreaEstablishing a new paradigm of the pathogenesis of diseases through the understanding of stem cell aging
Project/Area Number 26115006
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionNational Cancer Center Japan (2018)
Kyushu University (2014-2017)

Principal Investigator

HAENO HIROSHI  国立研究開発法人国立がん研究センター, 先端医療開発センター, 特任研究員 (70706754)

Project Period (FY) 2014-07-10 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥43,810,000 (Direct Cost: ¥33,700,000、Indirect Cost: ¥10,110,000)
Fiscal Year 2018: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2017: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2016: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2015: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2014: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Keywords数理モデル / 確率過程 / シミュレーション解析 / がん進化 / 幹細胞老化 / ステムセルエイジング / 発がん過程 / 数理モデル研究
Outline of Final Research Achievements

We constructed a mathematical model of a hierarchical tissue from a stem cell population to functional cell populations. By performing comprehensive stochastic simulations, the process of cancer initiation through the tissue collapse was thoroughly investigated. We also obtained experimental data about tissue kinetics of hematopoietic tissue and colon tissue, and incorporated them to the model. As a result, we found that when the number and the cell division rate of a stem cell population is small and low, respectively, the time until cancer initiation becomes long. Finally we revealed the relationship between the complexity of a tissue and the feasibility of cancer initiation.

Academic Significance and Societal Importance of the Research Achievements

老化関連疾患としてのがんについて、組織構造と発症のし易さの関係性を明らかにすることができた。このことによって、組織ごとに、加齢による細胞の代謝(入れ替わり)の変化と発がんリスクの関係を予測し、予防的措置を講じる必要性や最適な治療標的を示すことで、発症率の減少や治療奏功率の上昇に役立つことが期待される。また、疾患の数理モデル研究の特集雑誌が日本で出版され始め、多くの特集に執筆を行うことで、ゲノム解析・細胞培養実験と合わせた数理モデル研究が注目を浴びることに貢献した。

Report

(6 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (29 results)

All 2019 2018 2017 2016 2015 2014 Other

All Int'l Joint Research (6 results) Journal Article (12 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 10 results,  Open Access: 8 results,  Acknowledgement Compliant: 3 results) Presentation (10 results) (of which Int'l Joint Research: 4 results) Book (1 results)

  • [Int'l Joint Research] Dana-Farber Cancer Institute/Massachusetts General Hospital(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Dana-Farber Cancer Institute(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Dana-Farber Cancer Institute/Memorial Sloan Kettering Cancer Center/Johns Hopkins Hospital(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Rutgers University(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] University of Southampton(United Kingdom)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Dana-Farbar Cancer Institute(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Computational modeling of pancreatic cancer patients receiving FOLFIRINOX and gemcitabine-based therapies identifies optimum intervention strategies2019

    • Author(s)
      Yamamoto Kimiyo N.、Nakamura Akira、Liu Lin L.、Stein Shayna、Tramontano Angela C.、Kartoun Uri、Shimizu Tetsunosuke、Inoue Yoshihiro、Asakuma Mitsuhiro、Haeno Hiroshi、Kong Chung Yin、Uchiyama Kazuhisa、Gonen Mithat、Hur Chin、Michor Franziska
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 4 Pages: e0215409-e0215409

    • DOI

      10.1371/journal.pone.0215409

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Stochastic Evolution of Pancreatic Cancer Metastases During Logistic Clonal Expansion2019

    • Author(s)
      Yamamoto Kimiyo N.、Liu Lin L.、Nakamura Akira、Haeno Hiroshi、Michor Franziska
    • Journal Title

      JCO Clinical Cancer Informatics

      Volume: 3 Issue: 3 Pages: 1-11

    • DOI

      10.1200/cci.18.00079

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mathematical modeling identifies optimum lapatinib dosing schedules for the treatment of glioblastoma patients2018

    • Author(s)
      Stein Shayna、Zhao Rui、Haeno Hiroshi、Vivanco Igor、Michor Franziska
    • Journal Title

      PLOS Computational Biology

      Volume: 14 Issue: 1 Pages: e1005924-e1005924

    • DOI

      10.1371/journal.pcbi.1005924

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Personalized Management of Pancreatic Ductal Adenocarcinoma Patients through Computational Modeling.2017

    • Author(s)
      Yamamoto KN, Yachida S, Nakamura A, Niida A, Oshima M, De S, Rosati LM, Herman JM, Iacobuzio-Donahue CA, Haeno H.
    • Journal Title

      Cancer Res.

      Volume: 77 Issue: 12 Pages: 3325-3335

    • DOI

      10.1158/0008-5472.can-16-1208

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Personalized Management of Pancreatic Ductal Adenocarcinoma Patients Through Computational Modeling.2017

    • Author(s)
      1.Yamamoto KN, Yachida S, Nakamura A, Niida A, Oshima M, De S, Rosati LM, Herman JM, Iacobuzio-Donahue CA, Haeno H
    • Journal Title

      Cancer Research

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Prediction of postoperative liver regeneration from clinical information using a data-led mathematical model.2016

    • Author(s)
      Yamamoto KN Ishii M, Inoue Y, Hirokawa F, MacArthur BD, Nakamura A, Haeno H, Uchiyama K.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 34214-34214

    • DOI

      10.1038/srep34214

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution.2016

    • Author(s)
      Uchi R, Takahashi Y, Niida A, Shimamura T, Hirata H, Sugimachi K, Sawada G, Iwaya T, Kurashige J, Shinden Y, Iguchi T, Eguchi H, Chiba K, Shiraishi Y, Nagae G, Yoshida K, Nagata Y, Haeno H et al.
    • Journal Title

      PLoS Genetics

      Volume: 12

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bacterial c-di-GMP affects hematopoietic stem/progenitors and their niches through STING.2015

    • Author(s)
      Kobayashi H, Kobayashi CI, Nakamura-Ishizu A, Karigane D, Haeno H, Yamamoto KN, Sato T, Ohteki T, Hayakawa Y, Barber GN, Kurokawa M, Suda T, and Takubo K.
    • Journal Title

      Cell Reports

      Volume: 111 Issue: 1 Pages: 71-84

    • DOI

      10.1016/j.celrep.2015.02.066

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The evolution of tumor metastasis during clonal expansion with alterations in metastasis driver genes2015

    • Author(s)
      Yamamoto KN, Nakamura A, Haeno H.
    • Journal Title

      Sci Rep

      Volume: 30:5 Issue: 1 Pages: 15886-15886

    • DOI

      10.1038/srep15886

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Evolution of Pre-Existing versus Acquired Resistance to Platinum Drugs and PARP Inhibitors in BRCA Associated Cancers2014

    • Author(s)
      Kimiyo N Yamamoto, Kouji Hirota, Shunichi Takeda, Hiroshi Haeno
    • Journal Title

      PLoS One

      Volume: 9

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] がんにおける突然変異蓄積過程の数理モデル解析2014

    • Author(s)
      波江野洋、山本君代
    • Journal Title

      実験医学増刊

      Volume: 32 Pages: 208-213

    • Related Report
      2014 Annual Research Report
  • [Journal Article] がん進展過程における薬剤耐性獲得の数理モデル2014

    • Author(s)
      波江野洋、山本君代
    • Journal Title

      がん分子標的薬治療

      Volume: 12 Pages: 72-77

    • Related Report
      2014 Annual Research Report
  • [Presentation] Computational modeling identifies optimal use of EGFR tyrosine kinase inhibitors for lung cancer patients with EGFR mutations2019

    • Author(s)
      Hiroshi Haeno
    • Organizer
      11th AACR-JCA Joint Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] データを用いたがんの数理モデル研究2018

    • Author(s)
      波江野洋
    • Organizer
      第15回生物数学の理論とその応用
    • Related Report
      2018 Annual Research Report
  • [Presentation] 個別化治療に向けた膵癌進展の数理モデル研究2018

    • Author(s)
      波江野洋
    • Organizer
      第29回日本消化器がん発生学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Personalized Management of Pancreatic Ductal Adenocarcinoma Patients Through Computational Modeling2017

    • Author(s)
      波江野洋
    • Organizer
      日本数理生物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Mathematical modeling of cancer and Cancer evolution2016

    • Author(s)
      Hiroshi Haeno
    • Organizer
      2016 Japanese Society for Mathematical Biology annual meeting
    • Place of Presentation
      九州大学
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 膵がん進行の数理モデル解析2016

    • Author(s)
      波江野洋
    • Organizer
      生命医薬情報学連合大会
    • Place of Presentation
      東京国際交流館プラザ平成
    • Related Report
      2016 Annual Research Report
  • [Presentation] Mathematical analysis on the genetic evolution from primary to metastatic tumor2015

    • Author(s)
      Hiroshi Haeno, Kimiyo N. Yamamoto, Subhajyoti De
    • Organizer
      The 74th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      日本・名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mathematical modeling of telomere length attrition in hematopoietic tissue2015

    • Author(s)
      Hiroshi Haeno, Honda Haruki
    • Organizer
      2015 Joint Meeting of The 5th China-Japan-Korea Colloquium on Mathematical Biology and The Japanese Society for Mathematical Biology
    • Place of Presentation
      日本・京都
    • Year and Date
      2015-08-26
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mathematical analysis on the genetic evolution from primary to metastatic tumor2014

    • Author(s)
      波江野洋、Subhojyoti De
    • Organizer
      日本消化器癌学会
    • Place of Presentation
      日本・福岡
    • Year and Date
      2014-11-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Genetic Evolution from primary to metastatic tumor2014

    • Author(s)
      Hiroshi Haeno, Subhojyoti De
    • Organizer
      Annual Meeting of the Japanese Society for Mathematical Biology and the Society for Mathematical Biology
    • Place of Presentation
      日本・大阪
    • Year and Date
      2014-07-28
    • Related Report
      2014 Annual Research Report
  • [Book] 実験医学増刊2017

    • Author(s)
      巌佐庸 波江野洋
    • Total Pages
      4
    • Publisher
      羊土社
    • Related Report
      2016 Annual Research Report

URL: 

Published: 2014-11-20   Modified: 2022-01-28  

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