Updated on 2025/09/30

写真a

 
KANO Mitsunobu
 
Organization
Faculty of Interdisciplinary Science and Engineering in Health Systems Professor
Position
Professor
Profile
臨床医の経験を通じて、身近に見出した課題を、基礎科学的に解き明かしていく研究やマネジメントを進めています。臨床、すなわち、身体症状という課題を抱えた方々を、科学という新しい知恵を確実にする方法を通じて、どうして差し上げたらよいか、という経験が原点にあるためです。現在の大きな柱は、主に研究面では1)膵がんをはじめとする薬物治療不応性の原因を、病巣組織構築に関連させナノテクノロジーや三次元培養等の新技術を応用し解析していく研究、2)医療ビッグデータを活用して、医療や疾病の全国的な状況を記述していく研究、そして主にマネジメント面では3)身近な疑問の集合体ともいえる国連のSDGs(持続可能な発展のための目標)を今後の研究活動の原動力としていくための大学運営、4)さらにこうした発想での研究活動も支援していくような政策の在り方を考える公的活動、などを進めています。
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Research Interests

  • Nano-pathophysiology

  • Science and Technology Policy

  • Issue-driven sciences

  • Epidemiology

Research Areas

  • Life Science / Experimental pathology

  • Life Science / Medical management and medical sociology

  • Life Science / Biomedical engineering

  • Life Science / General internal medicine

  • Life Science / Pharmacology

  • Life Science / Tumor diagnostics and therapeutics

  • Life Science / Biomaterials

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Education

  • The University of Tokyo    

    2002 - 2005

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  • The University of Tokyo    

    1995 - 1999

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  • The University of Tokyo    

    1993 - 1995

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Research History

  • Okayama University

    2024.4

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  • Okayama University

    2023.4

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  • International Science Council (ISC)   Fellow

    2023.3

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  • 文部科学省   主査

    2023.2

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  • 文部科学省   委員

    2023.2

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  • 文部科学省   主査代理

    2023.2

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  • Okayama University   Faculty of Pharmaceutical Sciences   Dean, Faculty of Pharmaceutical Sciences

    2022.4 - 2024.3

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  • Organization for Economic Cooperation and Development   Committee for Scientific and Technological Policy   Advisor, Transformative Agenda for STI Policy

    2021.3

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  • Science Council of Japan, Cabinet Office   第二部   Council Member

    2020.10

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  • Honda Foundation   Executive Director

    2019.4

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  • National Institutes for Quantum and Radiological Science and Technology

    2019.4

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  • Science and Technology Co-Advisor to the Minister for Foreign Affairs of Japan

    2019.4 - 2022.3

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  • Okayama University

    2018.4

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  • Okayama University Graduate School of Interdisciplinary Sciences and Engineering in Health Systems   Department of Pharmaceutical Biomedicine   Professor

    2018.4

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  • 文部科学省   委員

    2018.4

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  • Okayama University

    2017 - 2018

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  • 岡山大学医歯薬学総合研究科 副研究科長

    2016 - 2017

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  • 岡山大学医歯薬学総合研究科 教授

    2012 - 2018.3

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  • - Professor,Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,Okayama University

    2012

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  • 東京大学 医学部 MD研究者育成プログラム室・分子病理学 講師

    2008 - 2012

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  • Senior Assistant Professor

    2008 - 2012

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  • Assistant Professor

    2007 - 2008

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  • 東京大学 ナノバイオ・インテグレーション研究拠点・医学系研究科分子病理学 特任教員(助手・助教)

    2006 - 2008

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  • Research Associate

    2006 - 2007

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  • The University of Tokyo   Graduate School of Medicine

    2005 - 2006

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  • 東京大学医学部附属病院 (老年病学) 診療登録医

    2002 - 2005

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  • St. Luke's International University   St.Luke's International Hospital

    2002 - 2003

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  • St. Luke's International University   St.Luke's International Hospital

    1999 - 2002

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Professional Memberships

Committee Memberships

  • 文部科学省   科学技術・学術審議会 委員  

    2023.2   

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    Committee type:Government

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  • 文部科学省   科学技術・学術審議会 国際戦略委員会 主査代理  

    2023.2   

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    Committee type:Government

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  • 文部科学省   科学技術・学術審議会 人材委員会 主査  

    2023.2   

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    Committee type:Government

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  • 公益財団法人 アジア人口開発協会(APDA)   評議員  

    2023.6   

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    Committee type:Other

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  • JST   Program Officer on the STS Forum in the International Science and Technology Cooperation Infrastructure Development Programme  

    2022.7   

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    Committee type:Government

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  • Ministry of Foreign Affairs of Japan   Member, Science and Technology Diplomacy Advisory Committee  

    2022.4   

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    Committee type:Government

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  • The Japan Society of Drug Delivery System   President, Annual General Conference 2022, The Japan Society of Drug Delivery System  

    2021.6 - 2022.6   

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    Committee type:Academic society

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  • Science Council of Japan, Cabinet Office   Editorial Board, Trends in the Sciences  

    2020.10   

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    Committee type:Government

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  • Science Council of Japan, Cabinet Office   Secretary, Public Relations Committee  

    2020.10   

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    Committee type:Government

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  • Science Council of Japan, Cabinet Office   Head, Committee for strengthening national and international communications  

    2020.10   

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    Committee type:Government

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  • Ministry of Foreign Affairs   the Advisory Board for Promoting Science and Technology Diplomacy  

    2019.4 - 2022.3   

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    Committee type:Government

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  • Ministry of Foreign Affairs of Japan   Science and Technology Co-Advisor to Minister of Foreign Affairs  

    2019.4 - 2022.3   

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    Committee type:Government

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  • 京都大学   若手研究者戦略育成拠点(L-INSIGHT)アドバイザリーボード委員  

    2019   

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    Committee type:Other

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  • 日本DDS学会   理事  

    2018   

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    Committee type:Academic society

    日本DDS学会

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  • JST   External member, the Self Evaluation Committee  

    2018   

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  •   文部科学省 科学技術・学術政策局 科学技術イノベーション政策における「政策のための科学」アドバイザリー委員会 委員  

    2018   

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    Committee type:Government

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  •   外務省 科学技術外交委員会 SDGsスタディグループ メンバー(2018)  

    2018   

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  •   文部科学省 科学技術・学術審議会 臨時委員  

    2017 - 2023.2   

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    Committee type:Government

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  •   政策研究大学院大学 客員研究員  

    2017 - 2019   

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  •   文部科学省 基礎研究医養成活性化プログラム ペーパーレフェリー(2017-2018)  

    2017 - 2018   

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  •   文部科学省 ゲノム医療実現のための研究基盤の充実・強化に関する検討会(研究振興局ライフサイエンス課) 委員 (2017-2018)  

    2017 - 2018   

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  •   東北大学 学際科学フロンティア研究所 客員教授  

    2017 - 2018   

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  •   - 科学と社会研究会(日本学術協力財団) 会員(2017-)  

    2017   

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  • 日本学術協力財団   「学術の動向」編集委員  

    2016 - 2020.10   

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    Committee type:Academic society

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  •   公益財団法人国際高等研究所 基幹プログラム「将来の地球社会を考えたときの科学技術の在り方」 参加研究員(2015-2018)  

    2015 - 2018   

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  •   熊本大学大学院生命科学研究部 柴三郎プログラム 外部評価委員(2015-2017)  

    2015 - 2017   

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  • 科学技術振興機構(JST)   研究戦略開発センター(CRDS) 特任フェロー  

    2014 - 2024.3   

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  •   厚生労働省 戦略研究モニタリング 委員(2014-2017)  

    2014 - 2017   

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  •   日本学術会議 特任連携会員 ・若手アカデミー 副代表(2014-2017)  

    2014 - 2017   

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  •   JST バイオデータベースセンター(NDBC) 統合化推進プログラム 研究アドバイザー  

    2014 - 2017   

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  • 日本癌学会   評議員  

    2013   

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    Committee type:Academic society

    日本癌学会

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  •   文部科学省 未来医療研究人材養成推進委員会 ペーパーレフェリー(2013-2014)  

    2013 - 2014   

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  •   PLoS One アカデミックエディター(2012-2016)  

    2012 - 2016   

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  •   内閣府総合科学技術会議 ライフイノベーション戦略協議会 構成員  

    2012 - 2014   

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  •   文部科学省 新学術領域研究専門委員会 ナノメディシン専門委員会 委員(2012-2013)  

    2012 - 2013   

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  •   日本学術会議 連携会員  

    2011 - 2020.9   

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  •   Global Young Academy 委員(2014 執行委員)(2011-2017)  

    2011 - 2017   

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  •   Global Young Academy Member(2014 Member of the Executive Committee)(2011-2017)  

    2011 - 2017   

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  •   日本学術会議 特任連携会員 ・ 若手アカデミー委員会 副委員長 (2011-2014)  

    2011 - 2014   

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  • 日本DDS学会   評議員  

    2011   

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    Committee type:Academic society

    日本DDS学会

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  •   日本学術会議 特任連携会員 ・ 若手アカデミー委員会 若手アカデミー活動検討分科会幹事(2010-2011)  

    2010 - 2011   

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Papers

  • Targeting ROCK2 improves macromolecular permeability in a 3D fibrotic pancreatic cancer microenvironment model

    Hiroyoshi Y. Tanaka, Takuya Nakazawa, Takuya Miyazaki, Horacio Cabral, Atsushi Masamune, Mitsunobu R. Kano

    Journal of Controlled Release   369   283 - 295   2024.5

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    Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.jconrel.2024.03.041

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  • 肺動脈性肺高血圧症において肺動脈平滑筋細胞の過剰増殖に関わるPDGFシグナル経路の体系的解析

    中澤 拓也, 橋田 真穂, 木山 和子, 松原 広己, 狩野 光伸, 田中 啓祥

    国立病院総合医学会講演抄録集   77回   440 - 440   2023.10

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    Language:Japanese   Publisher:国立病院総合医学会  

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  • 積層培養技術による肺動脈壁の立体培養モデルの開発と肺高血圧症の病態進展機序の解析への応用

    和田 笑里, 木山 和子, 松原 広己, 狩野 光伸, 田中 啓祥

    国立病院総合医学会講演抄録集   77回   440 - 440   2023.10

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    Language:Japanese   Publisher:国立病院総合医学会  

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  • 慢性血栓塞栓性肺高血圧症(CTEPH)における器質化血栓の形成機序の解析および標的化法の開発

    桐石 奈月, 木山 和子, 松原 広己, 田中 啓祥, 狩野 光伸

    国立病院総合医学会講演抄録集   77回   440 - 440   2023.10

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    Language:Japanese   Publisher:国立病院総合医学会  

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  • Relationships between physical and immunological tumor microenvironment in pancreatic ductal adenocarcinoma

    Yu Igata, Motohiro Kojima, Toshiyuki Suzuki, Genichiro Ishii, Ryo Morisue, Toshihiro Suzuki, Masashi Kudo, Motokazu Sugimoto, Shin Kobayashi, John D. Martin, Triantafyllos Stylianopoulos, Horacio Cabral, Mitsunobu R. Kano, Masaru Konishi, Naoto Gotohda

    Cancer Science   114 ( 9 )   3783 - 3792   2023.9

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    Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/cas.15853

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  • Trends in Head and Neck Cancer Mortality from 1999 to 2019 in Japan: An Observational Analysis. International journal

    Tsukasa Higashionna, Keisaku Harada, Akinari Maruo, Takahiro Niimura, Elizabeth Tan, Quynh Thi Vu, Takayoshi Kawabata, Soichiro Ushio, Hirofumi Hamano, Makoto Kajizono, Yoshito Zamami, Keisuke Ishizawa, Ko Harada, Shiro Hinotsu, Mitsunobu R Kano, Hideharu Hagiya, Toshihiro Koyama

    Cancers   15 ( 15 )   2023.7

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    Language:English   Publishing type:Research paper (scientific journal)  

    Globally, the numbers of head and neck cancer (HNC) cases and related deaths have recently increased. In Japan, few studies have examined crude or age-adjusted HNC mortality rates. Therefore, this study aimed to determine the trends in crude and age-adjusted mortality rates for HNC per million individuals in Japan from 1999 to 2019. Data on HNC-associated deaths were extracted from the national death certificate database using the International Classification of Diseases, Tenth Revision (n = 156,742). HNC mortality trends were analysed using joinpoint regression models to estimate annual percentage change (APC) and average APC (AAPC). Among men, no significant change was observed in the age-adjusted death rate trend from 1999 to 2014; however, a marked decrease was observed from 2014 to 2019. No changing point was observed in women. Age-adjusted mortality rates continuously decreased over the 21-year period, with an AAPC of -0.7% in men and -0.6% in women. In conclusion, the overall trend in age-adjusted rates of HNC-associated deaths decreased, particularly among men, in the past 5 years. These results will contribute to the formulation of medical policies to develop targeted screening and prevention programmes for HNC in Japan and determine the direction of treatment strategies.

    DOI: 10.3390/cancers15153786

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  • Therapeutic Strategies to Overcome Fibrotic Barriers to Nanomedicine in the Pancreatic Tumor Microenvironment. International journal

    Hiroyoshi Y Tanaka, Takuya Nakazawa, Atsushi Enomoto, Atsushi Masamune, Mitsunobu R Kano

    Cancers   15 ( 3 )   2023.1

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    Pancreatic cancer is notorious for its dismal prognosis. The enhanced permeability and retention (EPR) effect theory posits that nanomedicines (therapeutics in the size range of approximately 10-200 nm) selectively accumulate in tumors. Nanomedicine has thus been suggested to be the "magic bullet"-both effective and safe-to treat pancreatic cancer. However, the densely fibrotic tumor microenvironment of pancreatic cancer impedes nanomedicine delivery. The EPR effect is thus insufficient to achieve a significant therapeutic effect. Intratumoral fibrosis is chiefly driven by aberrantly activated fibroblasts and the extracellular matrix (ECM) components secreted. Fibroblast and ECM abnormalities offer various potential targets for therapeutic intervention. In this review, we detail the diverse strategies being tested to overcome the fibrotic barriers to nanomedicine in pancreatic cancer. Strategies that target the fibrotic tissue/process are discussed first, which are followed by strategies to optimize nanomedicine design. We provide an overview of how a deeper understanding, increasingly at single-cell resolution, of fibroblast biology is revealing the complex role of the fibrotic stroma in pancreatic cancer pathogenesis and consider the therapeutic implications. Finally, we discuss critical gaps in our understanding and how we might better formulate strategies to successfully overcome the fibrotic barriers in pancreatic cancer.

    DOI: 10.3390/cancers15030724

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  • 多様な臓器から考える線維化治療への最先端アプローチ 三次元培養法による膵がん線維化組織のモデル化および筋線維芽細胞分化機序の解析

    中澤 拓也, 田中 啓祥, 狩野 光伸

    日本薬学会年会要旨集   142年会   GS02 - 3   2022.3

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  • “Issues” in clinical medicine and in society

    狩野光伸

    Drug Delivery System   37 ( 1 )   2022

  • 臨床試験実施可能性調査における被験者候補の効率的な絞り込み手法の検討

    岡崎 理紗, 奥田 浩人, 濱野 裕章, 難波 志穂子, 神川 邦久, 宇野 秀樹, 牛尾 聡一郎, 黒田 智, 座間味 義人, 狩野 光伸, 森田 瑞樹

    日本臨床薬理学会学術総会抄録集   43   3-C-P-095   2022

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    Language:Japanese   Publisher:一般社団法人 日本臨床薬理学会  

    【背景】臨床試験は新薬・新医療機器等の開発のみならず診療の最適化においても必要であり、文部科学省と厚生労働省は継続して臨床試験の活性化に取り組んできた。臨床試験の成功率を上げるために、臨床試験の受託前に、被験者となりうる患者の数(候補患者数)の見積もり調査が実施される。このような調査を行っているにも関わらず、調査に十分なリソースが割けないなどの理由から見積もりの精度が低くなり、臨床試験開始後に想定通り被験者が集まらないケースがある。このことが、臨床試験全体の遅れや中止による医薬品開発費の増大や科研費等の浪費につながっている。そこで、電子カルテのデータを用いた機械的な絞り込みを行うことによって被験者の候補者数の見積もりを効率化することで、被験者が想定通り集まらない事態を回避できるのではないかと考え、検討を行った。【目的】本研究では、電子カルテのデータを用いた機械的な患者絞り込みによって、候補患者数の見積もりが効率化されるか検討することを目的とした。【方法】一型糖尿病および潰瘍性大腸炎の臨床試験を対象とし、適格基準を満たす患者を以下の2つの方法で抽出した。(1)電子カルテのデータを用いた機械的な絞り込みを実施する。(2)臨床研究コーディネーター(CRC)によるカルテ調査を実施する。本研究では、(2)の方法で抽出された患者群を正解データとし、(1)の機械的な絞り込みの精度を求めた。【結果・考察】一型糖尿病では感度が37.5%となり、本来被験者候補とすべき症例をすべて網羅することができなかった。一方、潰瘍性大腸炎では感度が100%となり、被験者候補とすべき症例を漏れることなく抽出し、加えてカルテ調査をすべき症例数を約1/10に絞り込むことに成功した。このことから、CRCによるカルテ調査の前に機械的な絞り込みを実施するという運用を想定すると、被験者候補の抽出に要する時間を約1/10に短縮できる計算となった。【結論】潰瘍性大腸炎では、電子カルテのデータを用いた機械的な絞り込みが成功し、候補患者数の見積もりの効率化につながる結果が得られた。一方で、一型糖尿病に対する適応は困難であった。今後本研究手法の適合性を高めるために、成否に影響を与える疾患、臨床試験または適格基準の特徴について更なる調査と分析が必要である。

    DOI: 10.50993/jsptsuppl.43.0_3-c-p-095

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  • Trends in hepatitis C virus-associated mortality rates in Japan, 1998-2017. International journal

    Hideharu Hagiya, Toshihiro Koyama, Matsuo Deguchi, Yusuke Minato, Satomi Miura, Tomoko Funahashi, Yusuke Teratani, Yoshito Zamami, Kazuaki Shinomiya, Yoshihisa Kitamura, Toshiaki Sendo, Shiro Hinotsu, Mitsunobu Kano

    Journal of gastroenterology and hepatology   36 ( 9 )   2486 - 2492   2021.9

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    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND AND AIM: The current prevalence of hepatitis C virus infection and hepatitis C virus-associated mortality in Japan falls short of the World Health Organization goal of viral hepatitis elimination by 2030. We aimed to evaluate the trends in hepatitis C virus-associated mortality in Japan. METHODS: This nationwide observational study used the Japanese Vital Statistics from 1998 to 2017 and included all Japanese hepatitis C virus-associated deaths (84 936) of adults aged ≥ 40 years. We calculated the crude and age-standardized mortality rates per 100 000 persons by age and sex. Joinpoint regression analysis was used to identify significant changing points in trends and to estimate the annual percentage changes and the average annual percentage changes for the entire study period. RESULTS: The crude mortality rate per 100 000 persons (annual death number) increased from 5.5 (3548) in 1998 to 7.0 (4843) in 2005 and decreased to 4.0 (3095) in 2017. By 2017, the crude mortality rates per 100 000 persons among men and women had dropped to 3.6 and 4.3, respectively. The age-standardized mortality rate was higher in women than in men. The average annual percentage change was -3.8% (95% confidence interval: -5.0 to -2.5). The declining trend was more rapid in men (-4.5%, 95% confidence interval: -5.3 to -3.6) than in women (-2.7%, 95% confidence interval: -3.8 to -1.6). CONCLUSIONS: Trends in hepatitis C virus-associated mortality rates have declined in an accelerating manner in Japan, especially among men.

    DOI: 10.1111/jgh.15517

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  • Fibrotic elements within the tumor microenvironment and its implications for nano-drug delivery systems

    田中啓祥, 狩野光伸

    Drug Delivery System   36 ( 4 )   232 - 240   2021.9

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    Language:Japanese  

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  • 線維化量を制御可能なヒト膵がん微小環境の三次元培養モデルの確立・解析とナノDDS研究への応用

    田中 啓祥, 狩野 光伸

    日本DDS学会学術集会プログラム予稿集   37回   115 - 115   2021.6

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  • Population-Based Observational Study of Adverse Drug Event-Related Mortality in the Super-Aged Society of Japan. International journal

    Tomoko Funahashi, Toshihiro Koyama, Hideharu Hagiya, Ko Harada, Syunya Iinuma, Soichiro Ushio, Yoshito Zamami, Takahiro Niimura, Kazuaki Shinomiya, Keisuke Ishizawa, Toshiaki Sendo, Shiro Hinotsu, Mitsunobu R Kano

    Drug safety   44 ( 5 )   531 - 539   2021.5

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    INTRODUCTION: Adverse drug events (ADEs) are a major cause of mortality. OBJECTIVE: We examined long-term trends for ADE-related deaths in Japan. METHODS: This observational study was conducted using the Japanese Vital Statistics from 1999 to 2016. Data for all ADE-related deaths were extracted using International Classification of Diseases, Tenth Revision codes. We analysed ADE-related deaths by age and sex and calculated crude and age-standardised mortality rates (ASMR) per 100,000 people. We used Joinpoint regression analysis to identify significant changing points in mortality trends and to estimate annual percentage change (APC). RESULTS: In total, 16,417 ADE-related deaths were identified. The crude mortality rate for individuals aged ≥ 65 years was higher than that of young individuals. The ASMR per 100,000 people increased from 0.44 in 1999 to 0.64 in 2016. The crude mortality rate increased from 0.44 in 1999 to 1.01 in 2016. The APC of ASMR increased at a rate of 2.8% (95% confidence interval [CI] 1.4-4.2) throughout the study period. In addition, crude mortality increased at a rate of 5.7% (95% CI 4.2-7.3) annually from 1999 to 2016. The ADE-related mortality rate was higher for men than for women during the study period. CONCLUSIONS: The number of and trend in ADE-related deaths increased in Japan from 1999 to 2016, particularly in the older population.

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  • Biomaterials from the Perspective of SDGs: How can Science Contribute to the SDGs?

    狩野光伸

    バイオマテリアル(Web)   39 ( 3 )   2021

  • p53発現による線維性微小環境の再プログラム化は膵臓癌における腫瘍融解ウイルス療法の治療効果を増強する

    西山岳芳, 田澤大, 田澤大, 梶原義典, 庄司良平, 永井康雄, 菊地覚次, 黒田新士, 黒田新士, 野間和広, 吉田龍一, 西崎正彦, 田中啓祥, 狩野光伸, 浦田泰生, 香川俊輔, 藤原俊義

    日本癌学会学術総会抄録集(Web)   80th   2021

  • 難治性呼吸器疾患・肺高血圧症に関する調査研究 三次元培養技術による肺動脈性肺高血圧症の新規治療薬探索

    小川愛子, 森井千春, 田中啓祥, 出石恭久, 中尾なつみ, 山本雅哉, 松原広己, 狩野光伸

    難治性呼吸器疾患・肺高血圧症に関する調査研究 令和2年度 研究報告書(Web)   2021

  • Selection of Tumor models

    Hiroki Takashima, Yoshikatsu Koga, Ryo Tsumura, Hirobumi Fuchigami, Yasuhiro Matsumura, Masahiro Yasunaga, Hiroyoshi Y. Tanaka, Tsuyoshi Kurihara, Mitsunobu R. Kano

    Drug Delivery System   35 ( 5 )   443 - 447   2020.11

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    DOI: 10.2745/dds.35.443

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  • 線維化量を自在に可変なヒト膵がん微小環境の三次元培養モデルの確立および解析

    田中 啓祥, 正宗 淳, 狩野 光伸

    日本癌学会総会記事   79回   OE14 - 8   2020.10

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  • 膵臓がん線維化組織の3D培養モデルを利用したナノ薬剤送達効率の解析

    田中 啓祥, 狩野 光伸

    日本DDS学会学術集会プログラム予稿集   36回   172 - 172   2020.8

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  • 日本人高齢者における転倒関連死 死亡統計データを用いた20年間のトレンド解析

    萩谷 英大, 小山 敏広, 樂木 宏実, 狩野 光伸

    日本老年医学会雑誌   57 ( Suppl. )   68 - 68   2020.7

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  • Trends in the nontuberculous mycobacterial disease mortality rate in Japan: A nationwide observational study, 1997-2016. Reviewed International journal

    Ko Harada, Hideharu Hagiya, Tomoko Funahashi, Toshihiro Koyama, Mitsunobu R Kano, Fumio Otsuka

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America   73 ( 2 )   e321-e326   2020.6

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    BACKGROUND: The incidence of nontuberculous mycobacterial (NTM) infections has been increasing worldwide, becoming a significant healthcare burden especially among elderly people. This study aimed to evaluate the trends in NTM-associated mortality in Japan. METHODS: This study used vital statistics data and data on all NTM-associated deaths (N=18,814) among individuals aged ≥40 years in Japan from 1997 to 2016. We calculated the crude and age-adjusted mortality rates by age and sex and used joinpoint regression to analyze trends and estimate the average annual percentage change (AAPC). We compared crude NTM- and tuberculosis (TB)-associated mortality rates by sex. RESULTS: The overall crude annual mortality rate increased from 0.63/100,000/year in 1997 to 1.93/100,000/year in 2016 and was the highest among individuals aged 80-84 years. The AAPC of the crude mortality rates among males of all ages and females aged 40-59 years were stable but increased among females aged 60-79 years (3.5%, 95% confidence interval [CI]: 2.8-4.3%) and ≥80 years (4.3%, 95% CI: 3.7-4.9%). Among males, the age-adjusted mortality rates did not show a significant trend, while among females, the rates increased over the study period (AAPC: 4.6%, 95% CI: 2.7-6.6%). In females, the crude NTM-associated mortality rate exceeded the TB mortality rate in 2014, 2015, and 2016. CONCLUSIONS:  NTM mortality increased in Japan between 1997 and 2016, especially among the elderly female population. Given the increasing NTM-associated mortality and susceptible aging population, public health authorities in Japan should pay greater attention to NTM infections.

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  • 3D in vitro Model of Vascular Medial Thickening in Pulmonary Arterial Hypertension International journal

    Chiharu Morii, Hiroyoshi Y. Tanaka, Yasuhisa Izushi, Natsumi Nakao, Masaya Yamamoto, Hiromi Matsubara, Mitsunobu R. Kano, Aiko Ogawa

    FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY   8   482 - 482   2020.5

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    DOI: 10.3389/fbioe.2020.00482

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  • Heterotypic 3D pancreatic cancer model with tunable proportion of fibrotic elements. Reviewed International journal

    Hiroyoshi Y Tanaka, Tsuyoshi Kurihara, Takuya Nakazawa, Michiya Matsusaki, Atsushi Masamune, Mitsunobu R Kano

    Biomaterials   251   120077 - 120077   2020.4

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    Pancreatic ductal adenocarcinoma (PDAC) is an often lethal disease characterized by a dense, fibrotic stroma. However, the lack of relevant preclinical models that recapitulate the characteristic histopathology of human PDAC in vitro impedes the development of novel therapies. The amount of stromal elements differ largely within and between patients, but in vitro models of human PDAC often do not account for this heterogeneity. Indeed, analyses of human PDAC histopathology revealed that the proportion of stroma ranged from 40 to 80% across patients. We, therefore, generated a novel 3D model of human PDAC, consisting of co-cultured human PDAC tumor cells and fibroblasts/pancreatic stellate cells, in which the proportion of fibrotic elements can be tuned across the clinically observed range. Using this model, we analyzed the signaling pathways involved in the differentiation of myofibroblasts, a characteristic subpopulation of fibroblasts seen in PDAC. We show that both YAP and SMAD2/3 in fibroblasts are required for myofibroblastic differentiation and that both shared and distinct signaling pathways regulate the nuclear localization of these factors during this process. Our novel model will be useful in promoting the understanding of the complex mechanisms by which the fibrotic stroma develops and how it might be therapeutically targeted.

    DOI: 10.1016/j.biomaterials.2020.120077

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  • Antibiotic prescriptions for Japanese outpatients with acute respiratory tract infections (2013-2015): A retrospective Observational Study. Reviewed International journal

    Toshihiro Koyama, Hideharu Hagiya, Yusuke Teratani, Yasuhisa Tatebe, Ayako Ohshima, Mayu Adachi, Tomoko Funahashi, Yoshito Zamami, Hiroyoshi Y Tanaka, Ken Tasaka, Kazuaki Shinomiya, Yoshihisa Kitamura, Toshiaki Sendo, Shiro Hinotsu, Mitsunobu R Kano

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   26 ( 7 )   660 - 666   2020.3

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    OBJECTIVES: Appropriate antibiotic prescriptions for outpatients with acute respiratory tract infections (ARTIs) are urgently needed in Japan. However, the empirical proof of this need is under-documented. Therefore, we aimed to determine antibiotic prescription rates, and the proportions of antibiotic classes prescribed for Japanese patients with ARTIs. METHODS: We analysed health insurance claims data over 2013-2015 among Japanese patients aged <75 years and determined the following indicators: 1) visit rates for patients with ARTIs and antibiotic prescription rates per 1000 person-years, and 2) proportion of visits by antibiotic-prescribed patients with ARTIs. We defined broad-spectrum antibiotics using the WHO Anatomical Therapeutic Chemical classification 4 level codes. RESULTS: Among 8.65 million visits due to ARTIs at 6859 hospitals and 62,024 physicians' offices, the visit rate and antibiotic prescription rate per 1000 person-years were 990.6 (99% confidence interval [CI], 989.4-991.7) and 532.4 (99% CI, 531.6-533.3), respectively. The visit rates for patients aged 0-17, 18-59, and 60-74 years were 2410.0 (99% CI, 2407.2-2412.9), 683.6 (99% CI, 682.7-684.6), and 682.1 (99% CI, 678.2-686.0), and antibiotic prescription rates were 1093.3 (99% CI, 1091.4-1095.2), 434.1 (99% CI, 433.4-434.9), and 353.4 (99% CI, 350.7-356.1), respectively. The overall proportion of antibiotic prescriptions for ARTI visits was 52.7% and 91.3% of the antibiotics prescribed were broad-spectrum. CONCLUSIONS: Both the visit rates and antibiotic prescription rates for ARTIs were high in this Japanese cohort. The proportion of antibiotic prescriptions exceeded that recommended in the clinical guidelines. Thus, there might be a scope for reducing the current antibiotic prescription rate in Japan.

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  • A nationwide observational study of mortality trends related to adverse drug reactions in Japan

    船橋智子, 小山敏広, 萩谷英大, 原田洸, 寺谷祐亮, 座間味義人, 建部泰尚, 三上奈緒子, 大島礼子, 大島礼子, 四宮一昭, 北村佳久, 千堂年昭, 樋之津史郎, 狩野光伸

    日本薬学会年会要旨集(CD-ROM)   140年会   28X - am11   2020.3

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  • Trends in Place of Death in a Super-Aged Society: A Population-Based Study, 1998-2017. Reviewed International journal

    Toshihiro Koyama, Hideharu Hagiya, Tomoko Funahashi, Yoshito Zamami, Miyu Yamagishi, Hiroshi Onoue, Yusuke Teratani, Naoko Mikami, Kazuaki Shinomiya, Yoshihisa Kitamura, Toshiaki Sendo, Shiro Hinotsu, Mitsunobu R Kano

    Journal of palliative medicine   23 ( 7 )   950 - 956   2020.2

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    Background:
    Globally, the number of deaths is estimated to increase to 74 million per year by 2030. Place of death (PoD) is increasingly being recognized as an important aspect of end-of-life care. However, recent trends in PoD in Japan, one of the super-aged societies, are unknown.
    Objective:
    To analyze trends in PoD in Japan over two decades.
    Design:
    Population-based retrospective observational study.
    Setting:
    All deaths reported in Japan, 1998-2017. PoD was defined as hospital, nursing home, or own home.
    Results:
    All Japanese decedents (∼22.6 million) over the past 20 years were analyzed. The proportion of hospital deaths was consistently high (>80%), with a significant decreasing trend from the mid-2000s. Although the proportion of deaths at home decreased in the first half of the study period, they later increased. There was a low proportion of deaths in nursing homes compared to other places of death; however, the proportion increased continually throughout the study period, particularly among women. In 2015, more women died in nursing homes than at home. Although the proportion of hospital deaths declined in the second half of the study period, their overall number continued to increase, reflecting an increase in total deaths in Japan.
    Conclusions:
    This study highlighted rapid changes in trends in PoD in Japan, and the need to consider affordable end-of-life care in Japan as well as other countries with aging populations. The findings from this long-term epidemiological study provide important insights on this issue.

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  • Stromal barriers within the tumor microenvironment and obstacles to nanomedicine

    Hiroyoshi Y. Tanaka, Mitsunobu R. Kano

    Cancer Drug Delivery Systems Based on the Tumor Microenvironment   57 - 89   2020.1

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    DOI: 10.1007/978-4-431-56880-3_4

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  • Place of death trends among patients with dementia in Japan: a population-based observational study. Reviewed International journal

    Toshihiro Koyama, Misato Sasaki, Hideharu Hagiya, Yoshito Zamami, Tomoko Funahashi, Ayako Ohshima, Yasuhisa Tatebe, Naoko Mikami, Kazuaki Shinomiya, Yoshihisa Kitamura, Toshiaki Sendo, Shiro Hinotsu, Mitsunobu R Kano

    Scientific reports   9 ( 1 )   20235 - 20235   2019.12

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    Dementia is a major public health concern in ageing societies. Although the population of Japan is among the most aged worldwide, long-term trends in the place of death (PoD) among patients with dementia is unknown. In this Japanese nationwide observational study, we analysed trends in PoD using the data of patients with dementia who were aged ≥65 years and died during 1999-2016. Trends in the crude death rates and PoD frequencies were analysed using the Joinpoint regression model. Changes in these trends were assessed using the Joinpoint regression analysis in which significant change points, the annual percentage change (APC) and average APCs (AAPC) in hospitals, homes, or nursing homes were estimated. During 1999-2016, the number of deaths among patients with dementia increased from 3,235 to 23,757 (total: 182,000). A trend analysis revealed increased mortality rates, with an AAPC of 8.2% among men and 9.3% among women. Most patients with dementia died in the hospital, although the prevalence of hospital deaths decreased (AAPC: -1.0%). Moreover, the prevalence of nursing home deaths increased (AAPC: 5.6%), whereas the prevalence of home deaths decreased (AAPC: -5.8%). These findings support a reconsideration of the end-of-life care provided to patients with dementia.

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  • Fall-related mortality trends in older Japanese adults aged ≥65 years: a nationwide observational study. Reviewed International journal

    Hideharu Hagiya, Toshihiro Koyama, Yoshito Zamami, Yasuhisa Tatebe, Tomoko Funahashi, Kazuaki Shinomiya, Yoshihisa Kitamura, Shiro Hinotsu, Toshiaki Sendo, Hiromi Rakugi, Mitsunobu R Kano

    BMJ open   9 ( 12 )   e033462   2019.12

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    OBJECTIVES: Fall-related mortality among older adults is a major public health issue, especially for ageing societies. This study aimed to investigate current trends in fall-related mortality in Japan using nationwide population-based data covering 1997-2016. DESIGN: We analysed fall-related deaths among older persons aged ≥65 years using the data provided by the Japanese Ministry of Health, Labour and Welfare. RESULTS: The crude and age-standardised mortality rates were calculated per 100 000 persons by stratifying by age (65-74, 75-84 and ≥85 years) and sex. To identify trend changes, a joinpoint regression model was applied by estimating change points and annual percentage change (APC). The total number of fall-related deaths in Japan increased from 5872 in 1997 to 8030 in 2016, of which 78.8% involved persons aged ≥65 years. The younger population (65-74 years) showed continuous and faster-decreasing trends for both men and women. Average APC among men aged ≥75 years did not decrease. Among middle-aged and older women (75-84 and ≥85 years) decreasing trends were observed. Furthermore, the age-adjusted mortality rate of men was approximately twice that of women, and it showed a faster decrease for women. CONCLUSIONS: Although Japanese healthcare has shown improvement in preventing fall-related deaths over the last two decades, the crude mortality for those aged over 85 years remains high, indicating difficulty in reducing fall-related deaths in the super-aged population. Further investigations to uncover causal factors for falls in older populations are required.

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  • Oral anticoagulants usage in Japanese patients aged 18-74 years with non-valvular atrial fibrillation: a retrospective analysis based on insurance claims data. Reviewed International journal

    Ayako Ohshima, Toshihiro Koyama, Aiko Ogawa, Yoshito Zamami, Hiroyoshi Y Tanaka, Yoshihisa Kitamura, Toshiaki Sendo, Shiro Hinotsu, Michael W Miller, Mitsunobu R Kano

    Family practice   36 ( 6 )   685 - 692   2019.11

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    BACKGROUND: Oral anticoagulants use has increased rapidly, internationally. Here we look at risks and benefits, based on Japanese data, of therapy with low risk non-valvular atrial fibrillation patients. OBJECTIVES: Using a health insurance claims data set we assessed: (i) oral anticoagulants usage in Japan, and (ii) efficacy and safety of dabigatran compared with warfarin, in Japanese patients with non-valvular atrial fibrillation, aged 18-74 years. METHODS: We identified 4380 non-valvular atrial fibrillation patients treated with anticoagulants between 1 January 2005, and 28 February 2014, and estimated the adjusted hazard ratio for stroke or systemic embolism, and any hemorrhagic event (Cox proportional hazards regression model with stabilized inverse probability treatment weighting). RESULTS: The data included 101 989 anticoagulant prescriptions for 4380 patients, of which direct oral anticoagulants increased to 40.0% of the total by the end of the study. After applying exclusion criteria, 1536 new non-valvular atrial fibrillation patients were identified, including 1071 treated with warfarin and 465 with dabigatran. Mean ages were 56.11 ± 9.70 years for warfarin, and 55.80 ± 9.65 years for dabigatran. The adjusted hazard ratio (95% confidence interval), comparing dabigatran with warfarin, was 0.48 (0.25-0.91) for stroke or systemic embolism, and 0.91 (0.60-1.39) for any hemorrhage including intracranial and gastrointestinal. CONCLUSIONS: Number of patients prescribed direct oral anticoagulants steadily increased, and incidence of all-cause bleeding related to dabigatran was similar to warfarin, in our study population of younger non-valvular atrial fibrillation patients. Dabigatran, compared with warfarin, generally reduced risk of all-cause stroke and systemic embolism.

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  • ヒト膵がん由来膵星状細胞を用いた三次元膵がん線維化モデルの構築ならびに異常ECM改築の機序の解析(Pancreatic stellate cells from human pancreatic cancer show aberrant ECM remodeling in 3D engineered fibrotic tissue)

    田中 啓祥, 西原 広史, 正宗 淳, 狩野 光伸

    日本癌学会総会記事   78回   E - 3005   2019.9

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  • Pattern of antibiotic prescriptions for outpatients with acute respiratory tract infections in Japan, 2013-15: a retrospective observational study. Reviewed International journal

    Yusuke Teratani, Hideharu Hagiya, Toshihiro Koyama, Mayu Adachi, Ayako Ohshima, Yoshito Zamami, Hiroyoshi Y Tanaka, Yasuhisa Tatebe, Ken Tasaka, Naoko Mikami, Kazuaki Shinomiya, Yoshihisa Kitamura, Mitsunobu R Kano, Shiro Hinotsu, Toshiaki Sendo

    Family practice   36 ( 4 )   402 - 409   2019.7

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    BACKGROUND: In this age of antimicrobial resistance, unnecessary use of antibiotics to treat non-bacterial acute respiratory tract infections (ARTIs) and inappropriate use of antibiotics in treating bacterial ARTIs are public health concerns. PURPOSE: Our aim is to identify the pattern of oral antibiotic prescriptions for outpatients with ARTIs in Japan. METHODS: We analysed health insurance claims data of patients (aged ≤74 years) from 2013 to 2015, to determine the pattern of antibiotic prescriptions for outpatient ARTIs and calculated the proportion of each antibiotic. RESULTS: Data on 4.6 million antibiotic prescriptions among 1559394 outpatients with ARTIs were analysed. The most commonly prescribed classes of antibiotics included cephalosporins (41.9%), macrolides (32.8%) and fluoroquinolones (14.7%). The proportion of first-, second- and third-generation cephalosporins was 1.0%, 1.7% and 97.3%, respectively. Fluoroquinolones accounted for a quarter of the prescriptions for ARTIs in patients aged >20 years. In contrast, penicillins accounted for just 8.0% of the total number of antibiotic prescriptions for ARTIs. CONCLUSIONS: According to clinical guidelines, penicillins are first-line antibiotics against ARTIs. However, third-generation cephalosporins, macrolides and fluoroquinolones are more frequently prescribed in Japan. Although we could not assess the extent to which appropriate antibiotics are selected, our results support the necessity of improving antibiotic choices in the treatment of ARTIs.

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  • In vivo rendezvous of small nucleic acid drugs with charge-matched block catiomers to target cancers. Reviewed International journal

    Sumiyo Watanabe, Kotaro Hayashi, Kazuko Toh, Hyun Jin Kim, Xueying Liu, Hiroyuki Chaya, Shigeto Fukushima, Keisuke Katsushima, Yutaka Kondo, Satoshi Uchida, Satomi Ogura, Takahiro Nomoto, Hiroyasu Takemoto, Horacio Cabral, Hiroaki Kinoh, Hiroyoshi Y Tanaka, Mitsunobu R Kano, Yu Matsumoto, Hiroshi Fukuhara, Shunya Uchida, Masaomi Nangaku, Kensuke Osada, Nobuhiro Nishiyama, Kanjiro Miyata, Kazunori Kataoka

    Nature communications   10 ( 1 )   1894 - 1894   2019.4

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    Stabilisation of fragile oligonucleotides, typically small interfering RNA (siRNA), is one of the most critical issues for oligonucleotide therapeutics. Many previous studies encapsulated oligonucleotides into ~100-nm nanoparticles. However, such nanoparticles inevitably accumulate in liver and spleen. Further, some intractable cancers, e.g., tumours in pancreas and brain, have inherent barrier characteristics preventing the penetration of such nanoparticles into tumour microenvironments. Herein, we report an alternative approach to cancer-targeted oligonucleotide delivery using a Y-shaped block catiomer (YBC) with precisely regulated chain length. Notably, the number of positive charges in YBC is adjusted to match that of negative charges in each oligonucleotide strand (i.e., 20). The YBC rendezvouses with a single oligonucleotide in the bloodstream to generate a dynamic ion-pair, termed unit polyion complex (uPIC). Owing to both significant longevity in the bloodstream and appreciably small size (~18 nm), the uPIC efficiently delivers oligonucleotides into pancreatic tumour and brain tumour models, exerting significant antitumour activity.

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  • Association between rapid antigen detection tests and antibiotics for acute pharyngitis in Japan: A retrospective observational study. Reviewed International journal

    Yusuke Teratani, Hideharu Hagiya, Toshihiro Koyama, Ayako Ohshima, Yoshito Zamami, Yasuhisa Tatebe, Ken Tasaka, Kazuaki Shinomiya, Yoshihisa Kitamura, Toshiaki Sendo, Shiro Hinotsu, Mitsunobu R Kano

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   25 ( 4 )   267 - 272   2019.4

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    The application and clinical impact of rapid antigen detection test (RADT) in the treatment of acute pharyngitis is unknown in Japan. We aimed to examine the proportions of RADT usage to identify Group A β-hemolytic Streptococcus (GAS) in outpatients with acute pharyngitis and evaluate the association between RADT and antibiotic treatment. We analyzed health insurance claims data from 2013 to 2015. Logistic regression models were used to analyze associated factors with RADT, overall antibiotic prescription, or penicillin use. We analyzed 1.27 million outpatient visits with acute pharyngitis, in which antibiotics were prescribed in 59.3% of visits. Of the total visits, 5.6% of patients received RADT, and 10.8% of the antibiotics were penicillin. Penicillin selection rates were higher in cases with RADT (25.4%) than those without RADT (9.7%). Compared to large-scale facilities, antibiotic prescription rates were higher in physicians' offices. For factor analysis, age (3-15 years), diagnosis code (streptococcal pharyngitis), size of the medical facility (large-scale hospitals), and physician's specialty (pediatrics) were associated with RADT use. Penicillin selection rate increased with RADT implementation (25.4% vs. 9.7%: adjusted odds ratio 1.55; 95% CI, 1.50-1.60). At 63% of the facilities, the RADT implementation rate was <5% of acute pharyngitis visits prescribed antibiotics. In conclusion, the proportion of RADT usage for outpatients with acute pharyngitis was low in Japan. With appropriate indication and evaluation, we expect that more utilization of RADT can help promote antimicrobial stewardship for outpatients with acute pharyngitis by prompting penicillin therapy. Further investigation with detailed clinical data are warranted.

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  • Pancreatic stellate cells derived from human pancreatic cancer demonstrate aberrant SPARC-dependent ECM remodeling in 3D engineered fibrotic tissue of clinically relevant thickness. Reviewed International journal

    Hiroyoshi Y Tanaka, Kentaro Kitahara, Naoki Sasaki, Natsumi Nakao, Kae Sato, Hirokazu Narita, Hiroshi Shimoda, Michiya Matsusaki, Hiroshi Nishihara, Atsushi Masamune, Mitsunobu R Kano

    Biomaterials   192   355 - 367   2019.2

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    Desmoplasia is a hallmark of pancreatic cancer and consists of fibrotic cells and secreted extracellular matrix (ECM) components. Various in vitro three-dimensional (3D) models of desmoplasia have been reported, but little is known about the relevant thickness of the engineered fibrotic tissue. We thus measured the thickness of fibrotic tissue in human pancreatic cancer, as defined by the distance from the blood vessel wall to tumor cells. We then generated a 3D fibrosis model with a thickness reaching the clinically observed range using pancreatic stellate cells (PSCs), the main cellular constituent of pancreatic cancer desmoplasia. Using this model, we found that Collagen fiber deposition was increased and Fibronectin fibril orientation drastically remodeled by PSCs, but not normal fibroblasts, in a manner dependent on Transforming Growth Factor (TGF)-β/Rho-Associated Kinase (ROCK) signaling and Matrix Metalloproteinase (MMP) activity. Finally, by targeting Secreted Protein, Acidic and Rich in Cysteine (SPARC) by siRNA, we found that SPARC expression in PSCs was necessary for ECM remodeling. Taken together, we developed a 3D fibrosis model of pancreatic cancer with a clinically relevant thickness and observed aberrant SPARC-dependent ECM remodeling in cancer-derived PSCs.

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  • Search for Therapeutic Agents for Cardiac Arrest Using a Drug Discovery Tool and Large-Scale Medical Information Database. Reviewed International journal

    Yoshito Zamami, Takahiro Niimura, Toshihiro Koyama, Yuta Shigemi, Yuki Izawa-Ishizawa, Mizuki Morita, Ayako Ohshima, Keisaku Harada, Toru Imai, Hiromi Hagiwara, Naoto Okada, Mitsuhiro Goda, Kenshi Takechi, Masayuki Chuma, Yutaka Kondo, Koichiro Tsuchiya, Shiro Hinotsu, Mitsunobu R Kano, Keisuke Ishizawa

    Frontiers in pharmacology   10   1257 - 1257   2019

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    The survival rate of cardiac arrest patients is less than 10%; therefore, development of a therapeutic strategy that improves their prognosis is necessary. Herein, we searched data collected from medical facilities throughout Japan for drugs that improve the survival rate of cardiac arrest patients. Candidate drugs, which could improve the prognosis of cardiac arrest patients, were extracted using "TargetMine," a drug discovery tool. We investigated whether the candidate drugs were among the drugs administered within 1 month after cardiac arrest in data of cardiac arrest cases obtained from the Japan Medical Data Center. Logistic regression analysis was performed, with the explanatory variables being the presence or absence of the administration of those candidate drugs that were administered to ≥10 patients and the objective variable being the "survival discharge." Adjusted odds ratios for survival discharge were calculated using propensity scores for drugs that significantly improved the proportion of survival discharge; the influence of covariates, such as patient background, medical history, and treatment factors, was excluded by the inverse probability-of-treatment weighted method. Using the search strategy, we extracted 165 drugs with vasodilator activity as candidate drugs. Drugs not approved in Japan, oral medicines, and external medicines were excluded. Then, we investigated whether the candidate drugs were administered to the 2,227 cardiac arrest patients included in this study. The results of the logistic regression analysis showed that three (isosorbide dinitrate, nitroglycerin, and nicardipine) of seven drugs that were administered to ≥10 patients showed significant association with improvement in the proportion of survival discharge. Further analyses using propensity scores revealed that the adjusted odds ratios for survival discharge for patients administered isosorbide dinitrate, nitroglycerin, and nicardipine were 3.35, 5.44, and 4.58, respectively. Thus, it can be suggested that isosorbide dinitrate, nitroglycerin, and nicardipine could be novel therapeutic agents for improving the prognosis of cardiac arrest patients.

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  • 大学はSDGs達成にどのようにかかわれるか

    狩野光伸

    日本生物工学会大会講演要旨集   71st   2019

  • To Be Supported, or Not to Be: Images of Older People in Policy and the Reality in Local Communities in Japan. International journal

    Ken Aoo, Noriko Abe, Mitsunobu R Kano

    Frontiers in sociology   4   16 - 16   2019

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    Social innovation is not only about tangible new products, services, policies, and laws, but also about changes in societal perceptions, values, and norms. In Japan, current policies for older people, including Long-Term Care Insurance, tend to focus on medical and long-term care and other forms of "support" for older adults such as a pension. Naturally, these policies depict older adults as the "beneficiaries," or the ones in need of support. However, when we look back at pre-modern Japan, it was not always like that. Although older adults did depend on support from family and community members, they also played an active role as a laborer and caretaker as well as providing useful knowledge for their family and community. Moreover, currently, in different areas suffering from a sharp decline in population, such as Okayama prefecture in western Japan, older people are actually playing the role of the supporter for groups of people who are in need, not only the aged population but also other demographics including young children and parents. Based on this historic "tradition" and the present reality, this paper argues that we need to reestablish the image of (at least some) older people as capable of taking a more active and responsible role in society, and position them as such in the new "welfare society" systems in order to replace the conventional "welfare state" model.

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  • Trends in Polypharmacy in Japan: A Nationwide Retrospective Study. Reviewed International journal

    Hiroshi Onoue, Toshihiro Koyama, Yoshito Zamami, Hideharu Hagiya, Yasuhisa Tatebe, Naoko Mikami, Kazuaki Shinomiya, Yoshihisa Kitamura, Shiro Hinotsu, Toshiaki Sendo, Yasuyoshi Ouchi, Mitsunobu R Kano

    Journal of the American Geriatrics Society   66 ( 12 )   2267 - 2273   2018.12

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    OBJECTIVES: To describe and examine trends in polypharmacy according to age in Japan from 2010 to 2016. DESIGN: Retrospective observational study. SETTING: Outpatient settings. PARTICIPANTS: Japanese individuals aged 20 and older. MEASUREMENTS: We analyzed pharmacy claims data that the Japanese Ministry of Health, Labor, and Welfare provided in the Survey of Medical Care Activities in Public Health Insurance from 2010 to 2016. The use of 5 or more oral prescription medications per month was defined as polypharmacy and of 10 or more as excessive polypharmacy. Regression analysis was used to estimate trends in polypharmacy with annual percentage changes. Using number of medications (polypharmacy vs excessive polypharmacy), trends in polypharmacy and crude and age-adjusted rates of polypharmacy per 1,000 persons were calculated according to year and age group (20-34, 35-49, 50-64, 65-79, ≥ 80). RESULTS: We analyzed 240 million pharmacy claims data. The age-adjusted monthly prevalence rate of polypharmacy increased from 85.2 to 93.8 per 1,000 persons per month and of excessive polypharmacy from 13.6 to 14.0 per 1,000 persons per month from 2010 to 2016 in the entire study population. The highest rate of polypharmacy (per 1,000 persons) was observed in 2016 in those aged 80 and older (326.8), followed by those aged 65 to 79 (167.3). The polypharmacy rate increased by 6.3% (95% confidence interval (CI)=4.0-8.7) per year from 2010 to 2012, then decreased by 0.7% (95% CI=-1.3-0.0) per year from 2012 to 2016. The rate of excessive polypharmacy increased by 4.5% (95% CI=1.1-8.0) per year from 2010 to 2013 and then decreased by 3.7% (95% CI=-6.7 to -0.6) per year from 2013 to 2016. CONCLUSION: The overall trend of polypharmacy in Japan increased during the study period, although the increase ceased in 2013 and then declined from 2013 to 2016. Policy changes in Japan might be responsible for some of the changes. J Am Geriatr Soc 66:2267-2273, 2018.

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  • Trends in incidence and mortality of tuberculosis in Japan: a population-based study, 1997-2016. Reviewed International journal

    H Hagiya, T Koyama, Yoshito Zamami, Y Minato, Y Tatebe, N Mikami, Y Teratani, A Ohshima, K Shinomiya, Y Kitamura, T Sendo, S Hinotsu, K Tomono, R M Kano

    Epidemiology and infection   147   e38   2018.11

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    Japan is still a medium-burden tuberculosis (TB) country. We aimed to examine trends in newly notified active TB incidence and TB-related mortality in the last two decades in Japan. This is a population-based study using Japanese Vital Statistics and Japan Tuberculosis Surveillance from 1997 to 2016. We determined active TB incidence and mortality rates (per 100 000 population) by sex, age and disease categories. Joinpoint regression was applied to calculate the annual percentage change (APC) in age-adjusted mortality rates and to identify the years showing significant trend changes. Crude and age-adjusted incidence rates reduced from 33.9 to 13.9 and 37.3 to 11.3 per 100 000 population, respectively. Also, crude and age-adjusted mortality rates reduced from 2.2 to 1.5 and 2.8 to 1.0 per 100 000 population, respectively. Average APC in the incidence and mortality rates showed significant decline both in men (-6.2% and -5.4%, respectively) and women (-5.7% and -4.6%, respectively). Age-specific analysis demonstrated decreases in incidence and mortality rates for every age category, except for the incidence trend in the younger population. Although trends in active TB incidence and mortality rates in Japan have favourably decreased, the rate of decline is far from achieving TB elimination by 2035.

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  • In vitro 3D blood/lymph-vascularized human stromal tissues for preclinical assays of cancer metastasis. Reviewed International journal

    Akihiro Nishiguchi, Michiya Matsusaki, Mitsunobu R Kano, Hiroshi Nishihara, Daisuke Okano, Yoshiya Asano, Hiroshi Shimoda, Satoko Kishimoto, Soichi Iwai, Mitsuru Akashi

    Biomaterials   179   144 - 155   2018.10

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    DOI: 10.1016/j.biomaterials.2018.06.019

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  • Trends in Polypharmacy in Japan: A Nationwide Retrospective Study. Reviewed

    Onoue H, Koyama T, Zamami Y, Hagiya H, Tatebe Y, Mikami N, Shinomiya K, Kitamura Y, Hinotsu S, Sendo T, Ouchi Y, Kano MR

    Journal of the American Geriatrics Society   2018.10

  • Stromal barriers to nanomedicine penetration in the pancreatic tumor microenvironment. Reviewed International journal

    Hiroyoshi Y Tanaka, Mitsunobu R Kano

    Cancer science   109 ( 7 )   2085 - 2092   2018.7

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    DOI: 10.1111/cas.13630

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  • Stromal barriers to nanomedicine penetration in the pancreatic tumor microenvironment Reviewed

    Hiroyoshi Y. Tanaka, Mitsunobu R. Kano

    Cancer Science   109 ( 7 )   2085 - 2092   2018.7

  • Okayama University's Collective Response to Advance the SDGs Reviewed

    KANO Mitsunobu, INO Hideo, YOKOI Atsufumi, SATO Norito, TAKAHASHI Kayo, MAKINO Hirofumi

    TRENDS IN THE SCIENCES   23 ( 1 )   1_44 - 1_47   2018

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  • Hydrocortisone administration was associated with improved survival in Japanese patients with cardiac arrest. Reviewed International journal

    Takahiro Niimura, Yoshito Zamami, Toshihiro Koyama, Yuki Izawa-Ishizawa, Masashi Miyake, Tadashi Koga, Keisaku Harada, Ayako Ohshima, Toru Imai, Yutaka Kondo, Masaki Imanishi, Kenshi Takechi, Keijo Fukushima, Yuya Horinouchi, Yasumasa Ikeda, Hiromichi Fujino, Koichiro Tsuchiya, Toshiaki Tamaki, Shiro Hinotsu, Mitsunobu R Kano, Keisuke Ishizawa

    Scientific reports   7 ( 1 )   17919 - 17919   2017.12

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    DOI: 10.1038/s41598-017-17686-3

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  • Desmoplastic Reaction in 3D-Pancreatic Cancer Tissues Suppresses Molecular Permeability. Reviewed International journal

    Michiya Matsusaki, Misaki Komeda, Simona Mura, Hiroyoshi Y Tanaka, Mitsunobu R Kano, Patrick Couvreur, Mitsuru Akashi

    Advanced healthcare materials   6 ( 15 )   739 - 744   2017.8

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  • Regulation of endothelial Fas expression as a mechanism of promotion of vascular integrity by mural cells in tumors

    Ryosuke Kamei, Hiroyoshi Y. Tanaka, Takao Kawano, Chiharu Morii, Sayaka Tanaka, Hiroshi Nishihara, Caname Iwata, Mitsunobu R. Kano

    Cancer Science   108 ( 5 )   1080 - 1088   2017.5

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    DOI: 10.1111/cas.13216

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  • Regulation of endothelial Fas expression as a mechanism of promotion of vascular integrity by mural cells in tumors. Reviewed International journal

    Ryosuke Kamei, Hiroyoshi Y Tanaka, Takao Kawano, Chiharu Morii, Sayaka Tanaka, Hiroshi Nishihara, Caname Iwata, Mitsunobu R Kano

    Cancer science   108 ( 5 )   1080 - 1088   2017.5

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  • Vascular bursts enhance permeability of tumour blood vessels and improve nanoparticle delivery

    Yu Matsumoto, Joseph W. Nichols, Kazuko Toh, Takahiro Nomoto, Horacio Cabral, Yutaka Miura, R. James Christie, Naoki Yamada, Tadayoshi Ogura, Mitsunobu R. Kano, Yasuhiro Matsumura, Nobuhiro Nishiyama, Tatsuya Yamasoba, You Han Bae, Kazunori Kataoka

    NATURE NANOTECHNOLOGY   11 ( 6 )   533 - +   2016.6

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    DOI: 10.1038/NNANO.2015.342

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  • Vascular bursts enhance permeability of tumour blood vessels and improve nanoparticle delivery. Reviewed International journal

    Yu Matsumoto, Joseph W Nichols, Kazuko Toh, Takahiro Nomoto, Horacio Cabral, Yutaka Miura, R James Christie, Naoki Yamada, Tadayoshi Ogura, Mitsunobu R Kano, Yasuhiro Matsumura, Nobuhiro Nishiyama, Tatsuya Yamasoba, You Han Bae, Kazunori Kataoka

    Nature nanotechnology   11 ( 6 )   533 - 538   2016.6

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  • Increased fibrosis and impaired intratumoral accumulation of macromolecules in a murine model of pancreatic cancer co-administered with FGF-2. Reviewed International journal

    Satoshi Sakai, Caname Iwata, Hiroyoshi Y Tanaka, Horacio Cabral, Yasuyuki Morishita, Kohei Miyazono, Mitsunobu R Kano

    Journal of controlled release : official journal of the Controlled Release Society   230   109 - 15   2016.5

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  • Systemically Injectable Enzyme-Loaded Polyion Complex Vesicles as In Vivo Nanoreactors Functioning in Tumors. Reviewed International journal

    Yasutaka Anraku, Akihiro Kishimura, Mako Kamiya, Sayaka Tanaka, Takahiro Nomoto, Kazuko Toh, Yu Matsumoto, Shigeto Fukushima, Daiki Sueyoshi, Mitsunobu R Kano, Yasuteru Urano, Nobuhiro Nishiyama, Kazunori Kataoka

    Angewandte Chemie (International ed. in English)   55 ( 2 )   560 - 5   2016.1

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  • Systemically injectable enzyme-loaded polyion complex vesicles as in vivo nanoreactors functioning in tumors Reviewed

    Y. Anraku, A. Kishimura, M. Kamiya, S. Tanaka, T. Nomoto, K. Toh, Y. Matsumoto, S. Fukushima, D. Sueyoshi, M. R. Kano, Y. Urano, N. Nishiyama, K. Kataoka

    Angewandte Chemie International Edition   128 ( 2 )   570 - 575   2016.1

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  • Authentic Vascular and Stromal Structure in Animal Disease Model for Nanomedicine

    Hiroshi Nishihara, Mitsunobu R. Kano

    Intracellular Delivery III   149 - 160   2016

  • Density-tunable conjugation of cyclic RGD ligands with polyion complex vesicles for the neovascular imaging of orthotopic glioblastomas Reviewed

    Wataru Kawamura, Yutaka Miura, Daisuke Kokuryo, Kazuko Toh, Naoki Yamada, Takahiro Nomoto, Yu Matsumoto, Daiki Sueyoshi, Xueying Liu, Ichio Aoki, Mitsunobu R. Kano, Nobuhiro Nishiyama, Tsuneo Saga, Akihiro Kishimura, Kazunori Kataoka

    SCIENCE AND TECHNOLOGY OF ADVANCED MATERIALS   16 ( 3 )   035004   2015.6

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    DOI: 10.1088/1468-6996/16/3/035004

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  • Systemic Targeting of Lymph Node Metastasis through the Blood Vascular System by Using Size-Controlled Nano carriers Reviewed

    Horacio Cabral, Jun Makino, Yu Matsumoto, Peng Mi, Hailiang Wu, Takahiro Nomoto, Kazuko Toh, Naoki Yamada, Yuriko Higuchi, Satoshi Konishi, Mitsunobu R. Kano, Hiroshi Nishihara, Yutaka Miura, Nobuhiro Nishiyama, Kazunori Kataoka

    ACS NANO   9 ( 5 )   4957 - 4967   2015.5

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  • Secretions from placenta, after hypoxia/reoxygenation, can damage developing neurones of brain under experimental conditions Reviewed

    Daniel J. Curtis, Aman Sood, Tom J. Phillips, Veronica H. L. Leinster, Akihiro Nishiguchi, Christopher Coyle, Lizeth Lacharme-Lora, Oliver Beaumont, Helena Kemp, Roberta Goodall, Leila Cornes, Michele Giugliano, Rocco A. Barone, Michiya Matsusaki, Mitsuru Akashi, Hiroyoshi Y. Tanaka, Mitsunobu Kano, Jennifer McGarvey, Nagaraj D. Halemani, Katja Simon, Robert Keehan, William Ind, Tracey Masters, Simon Grant, Sharan Athwal, Gavin Collett, Dionne Tannetta, Ian L. Sargent, Emma Scull-Brown, Xun Liu, Kristian Aquilina, Nicki Cohen, Jon D. Lane, Marianne Thoresen, Jon Hanley, Andrew Randall, C. Patrick Case

    EXPERIMENTAL NEUROLOGY   261   386 - 395   2014.11

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  • Polymeric micelles loaded with platinum anticancer drugs target preangiogenic micrometastatic niches associated with inflammation Reviewed

    Hailiang Wu, Horacio Cabral, Kazuko Toh, Peng Mi, Yi-Chun Chen, Yu Matsumoto, Naoki Yamada, Xueying Liu, Hiroaki Kinoh, Yutaka Miura, Mitsunobu R. Kano, Hiroshi Nishihara, Nobuhiro Nishiyama, Kazunori Kataoka

    JOURNAL OF CONTROLLED RELEASE   189   1 - 10   2014.9

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    DOI: 10.1016/j.jconrel.2014.06.018

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  • Nanotechnology and tumor microcirculation Reviewed

    Mitsunobu R. Kano

    ADVANCED DRUG DELIVERY REVIEWS   74   2 - 11   2014.7

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  • Nano-pathophysiology: A novel integrated approach to disease through application of nanotechnology Preface Reviewed

    Mitsunobu R. Kano

    ADVANCED DRUG DELIVERY REVIEWS   74   1 - 1   2014.7

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  • SPIO-PICsome: Development of a highly sensitive and stealth-capable MRI nano-agent for tumor detection using SPIO-loaded unilamellar polyion complex vesicles (PICsomes) (vol 169, pg 220, 2013) Reviewed

    Daisuke Kokuryo, Yasutaka Anraku, Akihiro Kishimura, Sayaka Tanaka, Mitsunobu R. Kano, Jeff Kershaw, Nobuhiro Nishiyama, Tsuneo Saga, Ichio Aoki, Kazunori Kataoka

    JOURNAL OF CONTROLLED RELEASE   178   125 - 125   2014.3

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  • Targeted gene delivery by polyplex micelles with crowded PEG palisade and cRGD moiety for systemic treatment of pancreatic tumors Reviewed

    Zhishen Ge, Qixian Chen, Kensuke Osada, Xueying Liu, Theofilus A. Tockary, Satoshi Uchida, Anjaneyulu Dirisala, Takehiko Ishii, Takahiro Nomoto, Kazuko Toh, Yu Matsumoto, Makoto Oba, Mitsunobu R. Kano, Keiji Itaka, Kazunori Kataoka

    BIOMATERIALS   35 ( 10 )   3416 - 3426   2014.3

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  • Building Experimental System Modeling Fibrotic Tissue in Human Pancreatic Cancer by Three-Dimensional Layer-by-Layer Culture

    Mitsunobu R. Kano

    Engineered Cell Manipulation for Biomedical Application.   175 - 181   2014

  • Cyclic RGD-Linked Polymeric Micelles for Targeted Delivery of Platinum Anticancer Drugs to Glioblastoma through the Blood-Brain Tumor Barrier Reviewed

    Yutaka Miura, Tomoya Takenaka, Kazuko Toh, Shourong Wu, Hiroshi Nishihara, Mitsunobu R. Kano, Yasushi Ino, Takahiro Nomoto, Yu Matsumoto, Hiroyuki Koyama, Horacio Cabral, Nobuhiro Nishiyama, Kazunori Kataoka

    ACS NANO   7 ( 10 )   8583 - 8592   2013.10

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  • SPIO-PICsome: Development of a highly sensitive and stealth-capable MRI nano-agent for tumor detection using SPIO-loaded unilamellar polyion complex vesicles (PICsomes) Reviewed

    Daisuke Kokuryo, Yasutaka Anraku, Akihiro Kishimura, Sayaka Tanaka, Mitsunobu R. Kano, Jeff Kershaw, Nobuhiro Nishiyama, Tsuneo Saga, Ichio Aoki, Kazunori Kataoka

    JOURNAL OF CONTROLLED RELEASE   169 ( 3 )   220 - 227   2013.8

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  • Targeted therapy of spontaneous murine pancreatic tumors by polymeric micelles prolongs survival and prevents peritoneal metastasis Reviewed

    Horacio Cabral, Mami Murakami, Hironori Hojo, Yasuko Terada, Mitsunobu R. Kano, Ung-Il Chung, Nobuhiro Nishiyama, Kazunori Kataoka

    Proceedings of the National Academy of Sciences of the United States of America   110 ( 28 )   11397 - 11402   2013.7

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  • SPIO-loaded unilamellar polyion complex vesicles (SPIO-Cy5-PICsomes) as a high relaxivity contrast agent for tumor detection Reviewed

    D. Kokuryo, Y. Anraku, A. Kishimura, M. R Kano, S. Tanaka, T. Saga, I. Aoki, K. Kataoka

    Proc. 21th ISMRM Scientific Meeting and Exhibition   1869 - 1869   2013.4

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  • Transcription Factor YY1 Contributes to Tumor Growth by Stabilizing Hypoxia Factor HIF-1 alpha in a p53-Independent Manner Reviewed

    Shourong Wu, Vivi Kasim, Mitsunobu R. Kano, Sayaka Tanaka, Shinsuke Ohba, Yutaka Miura, Kanjiro Miyata, Xueying Liu, Ako Matsuhashi, Ung-il Chung, Li Yang, Kazunori Kataoka, Nobuhiro Nishiyama, Makoto Miyagishi

    CANCER RESEARCH   73 ( 6 )   1787 - 1799   2013.3

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    DOI: 10.1158/0008-5472.CAN-12-0366

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  • PDGFR beta expression in tumor stroma of pancreatic adenocarcinoma as a reliable prognostic marker Reviewed

    Sayaka Yuzawa, Mitsunobu R. Kano, Takahiro Einama, Hiroshi Nishihara

    MEDICAL ONCOLOGY   29 ( 4 )   2824 - 2830   2012.12

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    DOI: 10.1007/s12032-012-0193-0

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  • Homo-catiomer integration into PEGylated polyplex micelle from block-catiomer for systemic anti-angiogenic gene therapy for fibrotic pancreatic tumors Reviewed

    Qixian Chen, Kensuke Osada, Takehiko Ishii, Makoto Oba, Satoshi Uchida, Theofilus A. Tockary, Taisuke Endo, Zhishen Ge, Hiroaki Kinoh, Mitsunobu R. Kano, Keiji Itaka, Kazunori Kataoka

    BIOMATERIALS   33 ( 18 )   4722 - 4730   2012.6

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    DOI: 10.1016/j.biomaterials.2012.03.017

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  • Pericyte-Coverage of Human Tumor Vasculature and Nanoparticle Permeability Reviewed

    Liuzhe Zhang, Hiroshi Nishihara, Mitsunobu R. Kano

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   35 ( 5 )   761 - 766   2012.5

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  • Polymeric micelles incorporating (1,2-diaminocyclohexane)platinum (II) suppress the growth of orthotopic scirrhous gastric tumors and their lymph node metastasis Reviewed

    Md Rafi, H. Cabral, M. R. Kano, P. Mi, C. Iwata, M. Yashiro, K. Hirakawa, K. Miyazono, N. Nishiyama, K. Kataoka

    JOURNAL OF CONTROLLED RELEASE   159 ( 2 )   189 - 196   2012.4

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  • Engineering fibrotic tissue in pancreatic cancer: A novel three-dimensional model to investigate nanoparticle delivery Reviewed

    Hitomi Hosoya, Koji Kadowaki, Michiya Matsusaki, Horacio Cabral, Hiroshi Nishihara, Hideaki Ijichi, Kazuhiko Koike, Kazunori Kataoka, Kohei Miyazono, Mitsuru Akashi, Mitsunobu R. Kano

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   419 ( 1 )   32 - 37   2012.3

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    DOI: 10.1016/j.bbrc.2012.01.117

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  • NC-6301, a polymeric micelle rationally optimized for effective release of docetaxel, is potent but is less toxic than native docetaxel in vivo Reviewed

    Mitsunori Harada, Caname Iwata, Hiroyuki Saito, Kenta Ishii, Tatsuyuki Hayashi, Masakazu Yashiro, Kosei Hirakawa, Kohei Miyazono, Yasuki Kato, Mitsunobu R. Kano

    INTERNATIONAL JOURNAL OF NANOMEDICINE   7   2713 - 2727   2012

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    DOI: 10.2147/IJN.S31247

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  • NC-6301, a polymeric micelle rationally optimized for effective release of docetaxel, is potent but is less toxic than native docetaxel in vivo Reviewed

    Mitsunori Harada, Caname Iwata, Hiroyuki Saito, Kenta Ishii, Tatsuyuki Hayashi, Masakazu Yashiro, Kosei Hirakawa, Kohei Miyazono, Yasuki Kato, Mitsunobu R. Kano

    International Journal of Nanomedicine   7   2713 - 2727   2012

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    DOI: 10.2147/IJN.S31247

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  • Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size Reviewed

    H. Cabral, Y. Matsumoto, K. Mizuno, Q. Chen, M. Murakami, M. Kimura, Y. Terada, M. R. Kano, K. Miyazono, M. Uesaka, N. Nishiyama, K. Kataoka

    NATURE NANOTECHNOLOGY   6 ( 12 )   815 - 823   2011.12

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    DOI: 10.1038/NNANO.2011.166

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  • High Expression of IL-22 Suppresses Antigen-Induced Immune Responses and Eosinophilic Airway Inflammation via an IL-10-Associated Mechanism Reviewed

    Kazuyuki Nakagome, Mitsuru Imamura, Kimito Kawahata, Hiroaki Harada, Katsuhide Okunishi, Taku Matsumoto, Oh Sasaki, Ryoichi Tanaka, Mitsunobu R. Kano, He Chang, Haruo Hanawa, Jun-ichi Miyazaki, Kazuhiko Yamamoto, Makoto Dohi

    JOURNAL OF IMMUNOLOGY   187 ( 10 )   5077 - 5089   2011.11

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    DOI: 10.4049/jimmunol.1001560

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  • Transforming growth factor-beta decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells Reviewed

    S. Ehata, E. Johansson, R. Katayama, S. Koike, A. Watanabe, Y. Hoshino, Y. Katsuno, A. Komuro, D. Koinuma, M. R. Kano, M. Yashiro, K. Hirakawa, H. Aburatani, N. Fujita, K. Miyazono

    ONCOGENE   30 ( 14 )   1693 - 1705   2011.4

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    DOI: 10.1038/onc.2010.546

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  • Antiangiogenic gene therapy of experimental pancreatic tumor by sFlt-1 plasmid DNA carried by RGD-modified crosslinked polyplex micelles Reviewed

    Yelena Vachutinsky, Makoto Oba, Kanjiro Miyata, Shigehiro Hiki, Mitsunobu R. Kano, Nobuhiro Nishiyama, Hiroyuki Koyama, Kohei Miyazono, Kazunori Kataoka

    JOURNAL OF CONTROLLED RELEASE   149 ( 1 )   51 - 57   2011.1

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    DOI: 10.1016/j.jconrel.2010.02.002

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  • Improving Drug Potency and Efficacy by Nanocarrier-Mediated Subcellular Targeting Reviewed

    Mami Murakami, Horacio Cabral, Yu Matsumoto, Shourong Wu, Mitsunobu R. Kano, Takao Yamori, Nobuhiro Nishiyama, Kazunori Kataoka

    SCIENCE TRANSLATIONAL MEDICINE   3 ( 64 )   64ra2   2011.1

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    DOI: 10.1126/scitranslmed.3001385

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  • Polyplex micelles prepared from omega-cholesteryl PEG-polycation block copolymers for systemic gene delivery Reviewed

    Makoto Oba, Kanjiro Miyata, Kensuke Osada, R. James Christie, Mai Sanjoh, Weidong Li, Shigeto Fukushima, Takehiko Ishii, Mitsunobu R. Kano, Nobuhiro Nishiyama, Hiroyuki Koyama, Kazunori Kataoka

    BIOMATERIALS   32 ( 2 )   652 - 663   2011.1

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    DOI: 10.1016/j.biomaterials.2010.09.022

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  • 当院ICUにおける重症急性膵炎に対する栄養管理の工夫と問題点

    阿部克幸, 中村光伸, 宮崎大, 佐川俊彦, 木村恵美子, 金井郁実, 高橋由里子, 伊東七奈子, 山本淳子, 狩野江利加, 薊典代, 榎田泰明, 田中俊行, 小川哲史

    静脈経腸栄養   26 ( 1 )   2011

  • LPA(4) regulates blood and lymphatic vessel formation during mouse embryogenesis Reviewed

    Hayakazu Sumida, Kyoko Noguchi, Yasuyuki Kihara, Manabu Abe, Keisuke Yanagida, Fumie Hamano, Shinichi Sato, Kunihiko Tamaki, Yasuyuki Morishita, Mitsunobu R. Kano, Caname Iwata, Kohei Miyazono, Kenji Sakimura, Takao Shimizu, Satoshi Ishii

    BLOOD   116 ( 23 )   5060 - 5070   2010.12

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    DOI: 10.1182/blood-2010-03-272443

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  • Induction of Endothelial Nitric Oxide Synthase, SIRT1, and Catalase by Statins Inhibits Endothelial Senescence Through the Akt Pathway Reviewed

    Hidetaka Ota, Masato Eto, Mitsunobu R. Kano, Tomoaki Kahyo, Mitsutoshi Setou, Sumito Ogawa, Katsuya Iijima, Masahiro Akishita, Yasuyoshi Ouchi

    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY   30 ( 11 )   2205 - U411   2010.11

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    DOI: 10.1161/ATVBAHA.110.210500

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  • Exogenous introduction of tissue inhibitor of metalloproteinase 2 reduces accelerated growth of TGF-beta-disrupted diffuse-type gastric carcinoma Reviewed

    Erik Johansson, Akiyoshi Komuro, Caname Iwata, Akifumi Hagiwara, Yuma Fuse, Akira Watanabe, Yasuyuki Morishita, Hiroyuki Aburatani, Keiko Funa, Mitsunobu R. Kano, Kohei Miyazono

    CANCER SCIENCE   101 ( 11 )   2398 - 2403   2010.11

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    DOI: 10.1111/j.1349-7006.2010.01688.x

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  • Exogenous introduction of tissue inhibitor of metalloproteinase 2 reduces accelerated growth of TGF-β-disrupted diffuse-type gastric carcinoma Reviewed

    Erik Johansson, Akiyoshi Komuro, Caname Iwata, Akifumi Hagiwara, Yuma Fuse, Akira Watanabe, Yasuyuki Morishita, Hiroyuki Aburatani, Keiko Funa, Mitsunobu R. Kano, Kohei Miyazono

    International Journal of Psychoanalysis   91 ( 5 )   2398 - 2403   2010.10

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    DOI: 10.1111/j.1349-7006.2010.01688.x

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  • Enhanced in vivo Magnetic Resonance Imaging of Tumors by PEGylated Iron-Oxide-Gold Core-Shell Nanoparticles with Prolonged Blood Circulation Properties Reviewed

    Michiaki Kumagai, Tridib Kumar Sarma, Horacio Cabral, Sachiko Kaida, Masaki Sekino, Nicholas Herlambang, Kensuke Osada, Mitsunobu R. Kano, Nobuhiro Nishiyama, Kazunori Kataoka

    MACROMOLECULAR RAPID COMMUNICATIONS   31 ( 17 )   1521 - 1528   2010.9

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    DOI: 10.1002/marc.201000341

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  • Antiangiogenic Gene Therapy of Solid Tumor by Systemic Injection of Polyplex Micelles Loading Plasmid DNA Encoding Soluble Flt-1 Reviewed

    Makoto Oba, Yelena Vachutinsky, Kanjiro Miyata, Mitsunobu R. Kano, Sorato Ikeda, Nobuhiro Nishiyama, Keiji Itaka, Kohei Miyazono, Hiroyuki Koyama, Kazunori Kataoka

    MOLECULAR PHARMACEUTICS   7 ( 2 )   501 - 509   2010.3

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    DOI: 10.1021/mp9002317

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  • Treating "intractable" tumours using nanoDDS and TGF-beta inhibitor Reviewed

    Kano M.R, Nishihara H, Kataoka K, Miyazono K

    European Cells and Materials   20 ( SUPPL.3 )   2010

  • Enhanced magnetic resonance imaging of experimental pancreatic tumor in vivo by block copolymer-coated magnetite nanoparticles with TGF-beta inhibitor Reviewed

    Michiaki Kumagai, Mitsunobu R. Kano, Yasuyuki Morishita, Motomi Ota, Yutaka Imai, Nobuhiro Nishiyama, Masaki Sekino, Shoogo Ueno, Kohei Miyazono, Kazunori Kataoka

    JOURNAL OF CONTROLLED RELEASE   140 ( 3 )   306 - 311   2009.12

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    DOI: 10.1016/j.jconrel.2009.06.002

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  • Autophagy Is Activated by TGF-beta and Potentiates TGF-beta-Mediated Growth Inhibition in Human Hepatocellular Carcinoma Cells Reviewed

    Kunihiko Kiyono, Hiroshi I. Suzuki, Hironori Matsuyama, Yasuyuki Morishita, Akiyoshi Komuro, Mitsunobu R. Kano, Koichi Sugimoto, Kohei Miyazono

    CANCER RESEARCH   69 ( 23 )   8844 - 8852   2009.12

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    DOI: 10.1158/0008-5472.CAN-08-4401

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  • c-Ski overexpression promotes tumor growth and angiogenesis through inhibition of transforming growth factor-beta signaling in diffuse-type gastric carcinoma Reviewed

    Kunihiko Kiyono, Hiroshi I. Suzuki, Yasuyuki Morishita, Akiyoshi Komuro, Caname Iwata, Masakazu Yashiro, Kosei Hirakawa, Mitsunobu R. Kano, Kohei Miyazono

    CANCER SCIENCE   100 ( 10 )   1809 - 1816   2009.10

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    DOI: 10.1111/j.1349-7006.2009.01248.x

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  • Enhanced Percolation and Gene Expression in Tumor Hypoxia by PEGylated Polyplex Micelles Reviewed

    Muri Han, Makoto Oba, Nobuhiro Nishiyama, Mitsunobu R. Kano, Shinae Kizaka-Kondoh, Kazunori Kataoka

    MOLECULAR THERAPY   17 ( 8 )   1404 - 1410   2009.8

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    DOI: 10.1038/mt.2009.119

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  • Angiogenesis through Silencing Prolyl Hydroxylase Domain-2 Using Biocompatible Polyplex Nanocarrier Reviewed

    Shourong Wu, Nobuhiro Nishiyama, Keiji Itaka, Mitsunobu R. Kano, Yasuyuki Morishita, Kohei Miyazono, Ung-Il Chung, Kazunori Kataoka

    MOLECULAR THERAPY   17   S390 - S390   2009.5

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  • Diffuse-Type Gastric Carcinoma: Progression, Angiogenesis, and Transforming Growth Factor beta Signaling Reviewed

    Akiyoshi Komuro, Masakazu Yashiro, Caname Iwata, Yasuyuki Morishita, Erik Johansson, Yoshiko Matsumoto, Akira Watanabe, Hiroyuki Aburatani, Hiroyuki Miyoshi, Kunihiko Kiyono, Yo-taro Shirai, Hiroshi I. Suzuki, Kosei Hirakawa, Mitsunobu R. Kano, Kohei Miyazono

    JOURNAL OF THE NATIONAL CANCER INSTITUTE   101 ( 8 )   592 - 604   2009.4

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    DOI: 10.1093/jnci/djp058

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  • Comparison of the effects of the kinase inhibitors imatinib, sorafenib, and transforming growth factor-beta receptor inhibitor on extravasation of nanoparticles from neovasculature Reviewed

    Mitsunobu R. Kano, Yukari Komuta, Caname Iwata, Masako Oka, Yo-taro Shirai, Yasuyuki Morishita, Yasuyoshi Ouchi, Kazunori Kataoka, Kohei Miyazono

    CANCER SCIENCE   100 ( 1 )   173 - 180   2009.1

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    DOI: 10.1111/j.1349-7006.2008.01003.x

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  • Polyplex Micelles from Triblock Copolymers Composed of Tandemly Aligned Segments with Biocompatible, Endosomal Escaping, and DNA-Condensing Functions for Systemic Gene Delivery to Pancreatic Tumor Tissue Reviewed

    Kanjiro Miyata, Makoto Oba, Mitsunobu R. Kano, Shigeto Fukushima, Yelena Vachutinsky, Muri Han, Hiroyuki Koyama, Kohei Miyazono, Nobuhiro Nishiyama, Kazunori Kataoka

    PHARMACEUTICAL RESEARCH   25 ( 12 )   2924 - 2936   2008.12

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    DOI: 10.1007/s11095-008-9720-2

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  • Cilostazol inhibits oxidative stress-induced premature senescence via upregulation of Sirt1 in human endothelial cells Reviewed

    Hidetaka Ota, Masato Eto, Mitsunobu R. Kano, Sumito Ogawa, Katsuya Iijima, Masahiro Akishita, Yasuyoshi Ouchi

    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY   28 ( 9 )   1634 - 1639   2008.9

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    DOI: 10.1161/ATVBAHA.108.164368

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  • Enhancement of angiogenesis through stabilization of hypoxia-inducible factor-1 by silencing prolyl hydroxylase domain-2 gene Reviewed

    Shourong Wu, Nobuhiro Nishiyama, Mitsunobu R. Kano, Yasuyuki Morishita, Kohei Miyazono, Keiji Itaka, Ung-il Chung, Kazunori Kataoka

    MOLECULAR THERAPY   16 ( 7 )   1227 - 1234   2008.7

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    DOI: 10.1038/mt.2008.90

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  • Inhibition of endogenous TGF-beta signaling enhances lymphangiogenesis Reviewed

    Masako Oka, Caname Iwata, Hiroshi I. Suzuki, Kunihiko Kiyono, Yasuyuki Morishita, Tetsuro Watabe, Akiyoshi Kornuro, Mitsunobu R. Kano, Kohei Miyazono

    BLOOD   111 ( 9 )   4571 - 4579   2008.5

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    DOI: 10.1182/blood-2007-10-120337

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  • Inhibition of cyclooxygenase-2 suppresses lymph node metastasis via reduction of lymphangiogenesis Reviewed

    Caname Iwata, Mitsunobu R. Kano, Akiyoshi Komuro, Masako Oka, Kunihiko Kiyono, Erik Johansson, Yasuyuki Morishita, Masakazu Yashiro, Kosei Hirakawa, Michio Kaminishi, Kohei Miyazono

    CANCER RESEARCH   67 ( 21 )   10181 - 10189   2007.11

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    DOI: 10.1158/0008-5472.CAN-07-2366

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  • IL-5-induced hypereosinophilia suppiresses the antigen-induced immune response via a TGF-beta-dependent mechanism Reviewed

    Kazuyuki Nakagome, Makoto Dohi, Katsuhide Okunishi, Ryoichi Tanaka, Taku Kouro, Mitsunobu R. Kano, Kohei Miyazono, Jun-ichi Miyazaki, Kiyoshi Takatsu, Kazuhiko Yamamoto

    JOURNAL OF IMMUNOLOGY   179 ( 1 )   284 - 294   2007.7

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    DOI: 10.4049/jimmunol.179.1.284

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  • IL-5-induced hypereosinophilia suppiresses the antigen-induced immune response via a TGF-beta-dependent mechanism Reviewed

    Kazuyuki Nakagome, Makoto Dohi, Katsuhide Okunishi, Ryoichi Tanaka, Taku Kouro, Mitsunobu R. Kano, Kohei Miyazono, Jun-ichi Miyazaki, Kiyoshi Takatsu, Kazuhiko Yamamoto

    JOURNAL OF IMMUNOLOGY   179 ( 1 )   284 - 294   2007.7

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  • IL-5-induced hypereosinophilia suppiresses the antigen-induced immune response via a TGF-beta-dependent mechanism Reviewed

    Kazuyuki Nakagome, Makoto Dohi, Katsuhide Okunishi, Ryoichi Tanaka, Taku Kouro, Mitsunobu R. Kano, Kohei Miyazono, Jun-ichi Miyazaki, Kiyoshi Takatsu, Kazuhiko Yamamoto

    JOURNAL OF IMMUNOLOGY   179 ( 1 )   284 - 294   2007.7

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  • Improvement of cancer-targeting therapy, using nanocarriers for intractable solid tumors by inhibition of TGF-beta signaling Reviewed

    Mitsunobu R. Kano, Younsoo Bae, Caname Iwata, Yasuyuki Morishita, Masakazu Yashiro, Masako Oka, Tomoko Fujii, Akiyoshi Komuro, Kunihiko Kiyono, Michio Kaminishi, Kosei Hirakawa, Yasuyoshi Ouchi, Nobuhiro Nishiyama, Kazunori Kataoka, Kohei Miyazono

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   104 ( 9 )   3460 - 3465   2007.2

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    DOI: 10.1073/pnas.0611660104

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  • VEGF-A and FGF-2 synergistically promote neoangiogenesis through enhancement of endogenous PDGF-B-PDGFR beta signaling Reviewed

    MR Kano, Y Morishita, C Iwata, S Iwasaka, T Watabe, Y Ouchi, K Miyazono, K Miyazawa

    JOURNAL OF CELL SCIENCE   118 ( 16 )   3759 - 3768   2005.8

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    DOI: 10.1242/jcs.02483

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Books

  • SDGsの時代に探究・研究を進めるガイドブック : 社会からはじまり社会にめぐる、科学の考え方

    狩野, 光伸

    培風館  2022.6  ( ISBN:9784563019334

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    Total pages:xiv, 206p   Language:Japanese

    CiNii Books

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  • 論理的な考え方伝え方 : 根拠に基づく正しい議論のために

    狩野, 光伸

    慶應義塾大学出版会  2015.10  ( ISBN:9784766422672

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    Total pages:viii, 164p   Language:Japanese

    CiNii Books

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  • 論理的な考え方 伝え方 根拠に基づく正しい議論のために

    慶應義塾大学出版会  2015 

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Research Projects

  • Development of Functional Vascular Connected Organoid Transplantation Technology for Next Generation Regenerative Medicine

    Grant number:24H00787  2024.04 - 2028.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    山本 雅哉, 木村 剛, 長田 健介, 江草 宏, 狩野 光伸

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    Grant amount:\47710000 ( Direct expense: \36700000 、 Indirect expense:\11010000 )

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  • 膵がんの線維化障壁を克服するナノ薬物送達システム増強戦略の開発

    Grant number:23H02653  2023.04 - 2027.03

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    狩野 光伸, 正宗 淳

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    Grant amount:\18720000 ( Direct expense: \14400000 、 Indirect expense:\4320000 )

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  • Overcoming fibrotic barriers to nanomedicine delivery in pancreatic cancer

    Grant number:23K27344  2023.04 - 2027.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    狩野 光伸, 正宗 淳

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    Grant amount:\18720000 ( Direct expense: \14400000 、 Indirect expense:\4320000 )

    線維化は膵がんの特徴であり、病態進展や治療成績の重要な規定因子である。実際、異常増殖した膵臓星状細胞(Pancreatic Stellate Cell: PSC)とPSCが産生する多量のcollagen I等の細胞外基質(Extracellular Matrix: ECM)から成る線維化組織が、ナノ薬剤送達システム(ナノDDS)通過を妨げ、治療効果を弱めることを代表者らはこれまでに実証してきた。本研究では、こうした「線維化障壁」を克服する戦略の開発・確立を目指す。特に、膵がん線維化組織において高発現するマトリセルラーECMタンパク質と、PSCにおけるその受容体を介したシグナルに着目する。実際、R5年度には、マトリセルラーECMタンパク質が線維化障壁形成に関わることを示し、マトリセルラーECMタンパク質のシグナル伝達機序についての解析を推進した(投稿準備中)。当初計画していた内容に加え、線維化障壁形成に関わるPSCの細胞内伝達機序の解析も進捗があった。PSCにおいてキナーゼROCK2が線維化障壁形成に関わること、その標的化により薬剤送達効率を改善しうることを見出し、報告した(J Control Release 2024;369:283-95)。これらの知見を基盤に、線維化障壁の形成機序とその標的化法の確立に引き続き取り組んでいく。

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  • Development of a vascularized organoids transplantation technology for next-generation regenrative medicine

    Grant number:21H03814  2021.04 - 2024.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    山本 雅哉, 江草 宏, 狩野 光伸

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    Grant amount:\17680000 ( Direct expense: \13600000 、 Indirect expense:\4080000 )

    オルガノイドは、臓器機能の一部をもつミニ器官であり、再生医療や創薬を変革する技術として学術的・社会的に注目されている。一方、オルガノイドを患者の治療に利用する次世代再生医療を実現するためには、オルガノイド移植に対する技術革新が必要不可欠である。本研究では、体内におけるオルガノイド内の微小血管循環と機能維持とを高める方法論(血管連結オルガノイド移植技術)を学術的「問い」と定め、次世代再生医療における学術的課題を解決することを目指す。
    本研究目的を達成するために、研究期間を通じて、オルガノイドに対する微小血管導入技術、およびこの微小血管に対する体内微小血管連結技術を開発し、オルガノイド内の微小血管循環と機能維持とを評価する。具体的には、①サイズの小さいオルガノイドに対する微小血管導入技術、②可視化できない微小血管を連結するために、狙った位置に新しく血管を形成させることで位置を特定する細胞動員に基づく体内微小血管連結技術、③オルガノイド内の微小血管循環と機能維持との相関性の解明である。
    本研究目的を達成するために、以下の3つの研究課題について、それぞれ検討を進める。
    研究課題①オルガノイドに対する微小血管導入、研究課題②オルガノイドに対する体内微小血管連結、ならびに研究課題③血管連結オルガノイドの機能維持である。
    2021年度は、刺激応答性ハイドロゲルとして、細胞傷害性の低い糖が結合することによって水可溶化される糖刺激応答性ハイドロゲルを調製し、それから分岐構造をもつ鋳型を作製した。また、鋳型に対して血管内皮細胞を播種し、コラーゲンゲル内で血管内皮細胞を管腔状に維持したまま鋳型を除去できることを確認した。また、オルガノイドの前段階として、細胞凝集体を利用して、その内部に低分子化合物をデリバリーするための分子デリバリーシステムについても検討を行った。

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  • Clinical epidemiological study on disease structure and quality assessment of healthcare for the older population by utilizing healthcare big data

    Grant number:19K10533  2019.04 - 2022.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Koyama Toshihiro

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    Grant amount:\4290000 ( Direct expense: \3300000 、 Indirect expense:\990000 )

    The purpose of this study was to analyze the actual situation of medical care for the elderly from a long-term perspective by utilizing medical big data covering the entire population and integrating clinical epidemiological methods. As studies utilizing medical big data of the entire population targeting the elderly, we have clarified diseases that could be targeted, and published clinical epidemiological studies on influenza, heptitis C, adverse reaction-related deaths, amyloidosis, and sarcoidosis in international journals, respectively.

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  • Establishing a 3D model of fibrosis in pancreatic cancer and analysis of interaction between tumor cells and stellate cells

    Grant number:18H02797  2018.04 - 2022.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Kano Mitsunobu

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    Grant amount:\17160000 ( Direct expense: \13200000 、 Indirect expense:\3960000 )

    Our hypothesis is that fibrosis within tumour tissue is an important determinant of clinical drug efficacy. We worked on the verification of this hypothesis through three-dimensional culture of its constituent cells, pancreatic stellate cells (PSCs). Specifically, the thickness of fibrotic tissue was measured in human cases and three-dimensional cultured tissue with equivalent thickness was created. The ECM proteins involved in fibrosis were visualised and analysed in the fibrotic tissue model, and differences between pancreatic cancer-derived PSCs and normal fibroblasts were revealed. We developed a three-dimensional co-culture model between PSCs and pancreatic cancer cells, and succeeded in creating three-dimensional co-cultured tissue that reproduced the range of tumour tissue occupancy rates observed clinically. Consequently, we were able to reproduce and analyse mechanism of the acquisition of PSC trait abnormalities by co-culturing with pancreatic cancer cells.

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  • Analysis of downstream effectors of PDGF signaling to identify novel therapeutic targets in pulmonary hypertension

    Grant number:18K08128  2018.04 - 2021.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Matsubara Hiromi

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    Grant amount:\4420000 ( Direct expense: \3400000 、 Indirect expense:\1020000 )

    We studied the role of the transcription factor distal-less homeobox 1 (DLX1) in the proliferation of pulmonary arterial smooth muscle cells (PASMCs) isolated from patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Knockdown of DLX1 expression resulted in a marked reduction of PASMC proliferation at baseline as well as in the presence of platelet-derived growth factor (PDGF) ligands. Microarray analyses implicated reduced expression of integrin subunits as a mechanism underlying reduced PASMC proliferation upon DLX1 knockdown. Indeed, knockdown of the integrin subunit resulted in a reduced PASMC proliferation at baseline and in the presence of PDGF ligands. Furthermore, the respective ligand of the integrin subunit was elevated in the sera of PH patients compared to healthy controls. Altogether, our results suggest that DLX1, downstream of PDGF signaling, modulates integrin expression to promote PASMC proliferation in the pathogenesis of PH.

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  • Construction of flow culture system of 3D-Cancer-stromal Tissues for Evaluation of Interaction Between Cancer cells and Immunocytes

    Grant number:17H02099  2017.04 - 2020.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Matsusaki Michiya

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    Grant amount:\17680000 ( Direct expense: \13600000 、 Indirect expense:\4080000 )

    In this study, three-dimensional (3D)-cancer-stromal tissues containing immunocytes for flow culture system has been constructed by cell accumulation technology. Cancer tissue-originated spheroid (CTOS) has been embedded in the 3D tissues together with monocyte-derived dendritic cells for evaluation of CTOS-immunocyte interaction. Furthermore, sacrifacial gelan gum allowed construction of small blood vessel structure in the 3D tissues for flow culture. We also found that norteworthy synergistic effect of anticancer drugs and molecular targeting drugs has been evaluated by the 3D cancer-stromal tissues. Accordingly, this study has been successfully achieved as schedule.

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  • Development of a method for validating epidemiological research results using a large-scale claim database.

    Grant number:16K08910  2016.04 - 2020.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Hinotsu Shiro

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    Grant amount:\4810000 ( Direct expense: \3700000 、 Indirect expense:\1110000 )

    The claim database was obtained from JMDC. Between January 2005 and July 2017, there were 5,767 patients diagnosed prostate cancer. The total number of hospitals was 17,001, of which 14,487 (85.2%) were clinics with 0-19 beds. The total number of medical prescriptions was 1,426,115. Among them, the drugs used for the treatment of prostate cancer, 4,288 cases of Leuplin, 4,220 cases of Casodex tablets (6,680 generic products), 3,155 cases of Zoradex, and 1,028 cases of Odyne tablets (424 generic products). The total number of laboratory tests was 5,225,046, with Creatinine 91,672, AST 85,736, ALT 85,523, and PSA 7,877. It was considered that this large-data could be used to estimate the risk of adverse events occurring in renal and liver functions.

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  • Investigation of intractability of pancreatic cancer by using 3D culture of pancreatic stellate cells

    Grant number:26293119  2014.04 - 2018.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Mitsunobu Kano

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    Grant amount:\16120000 ( Direct expense: \12400000 、 Indirect expense:\3720000 )

    The 5-year survival rate of pancreatic cancer is approximately 10% and has not improved for 30 years. Especially in advanced pancreatic cancer, the prognosis is still less than 6 months. The fact suggests that the efficacy of the administered anti-tumor agents are not enough.
    In this study, we investigated the role of drug delivery pathway: via 1) tumor blood vessel and 2) tumor fibrous tissue.
    For the purpose we constructed a novel three dimensional culture system in this study using cells derived from human pancreatic cancer, especially pancreatic stellate cells (PSC) derived from human patients. We investigated the developed model from the viewpoint of molecular biology and behavior of nanomedicine. As a result, we were able to construct a method of three-dimensional culture / co-culture with reproducibility using PSC, and succeeded in using the model for the analysis of drug delivery.

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  • Fabrication of Innovative Human 3D-Tumor Models for In Vitro Evaluation of Cancer Growth, Invation, and Metastasis

    Grant number:26282138  2014.04 - 2017.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Matsusaki Michiya, KANO Mitsunobu

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    Grant amount:\14690000 ( Direct expense: \11300000 、 Indirect expense:\3390000 )

    In this research, in vitro 3D-human tumor models, reflecting tumor growth, invasion, and metastasis, was constructed by cell accumulation technique via fabrication of nanometer-sized extracellular matrix films on cell surface. This is the first report in the world about 3D-tumor tissue models which allow in vitro evaluation of cancer cell invasion into blood and lymph capillaries. Furthermore, extremely high drug resistance approximately 1000 times against anticancer drugs was found in 3D-tissue models as compared to that in 2D-culture. Since the 3D-models are now applying primary culture of patient's cancer cells, it is expected to apply in pharmaceutical and medical fields.

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  • Molecular Mechanisms in extravasation of nanoDDS

    Grant number:23790433  2011.04 - 2014.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

    KANO Mitsunobu

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    Grant amount:\4030000 ( Direct expense: \3100000 、 Indirect expense:\930000 )

    We have shown that characteristics of tumor vasculature can determine the intractability of tumors, and that manipulation of the vasculature characteristics can improve the efficacy of nanoDDS in the animal models of pancreatic and gastric cancers. In this study we focused on a protein, known to be expressed in neovasculature and stabilizing endothelial-mural cell attachment. The protein was suggested to play an important role in the mechanism of extravasation of nanoDDS from tumor vasculature.

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  • Enhancement of nanoparticle accumulation via regulation of tumor vasculature

    Grant number:19790282  2007 - 2008

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

    KANO Mitsunobu

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    Grant amount:\3780000 ( Direct expense: \3300000 、 Indirect expense:\480000 )

    我々はナノ粒子薬剤とTGF-β阻害剤の併用により難治固形癌の治療効率を高める可能性を示してきたが、本研究でその適応範囲を検討した。その結果、壁細胞被覆の多い新生血管はTGF-β阻害剤で漏出化し高分子物質の貯留が増加したが、被覆の少ない血管は、元来漏出性が高い上にVEGF 阻害剤で貯留が増加した。壁細胞被覆の多い新生血管は腫瘍モデルでは間質量の多い組織型のものに観察された。

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  • Establishment of New Strategies for Treatment of Cancer Using TGF-beta Signaling

    Grant number:17016011  2005 - 2009

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research on Priority Areas

    MIYAZONO Kohei, MIYAZAWA Keiji, IMAMURA Takeshi, MAEDA Shingo, WATABE Tetsuro, SAITOH Masao, KANO Mitsunobu, KOINUMA Daizo, EHATA Shogo

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    Grant amount:\345700000 ( Direct expense: \345700000 )

    TGF-βは強力な増殖抑制因子であるが、一方で上皮-間葉分化転換の促進などによりがんの浸潤・転移を促進する。本研究では、TGF-βシグナルの抑制が乳がんの転移を抑制し、脳腫瘍ではがん幹細胞の分化を促進することを示した。一方、スキルス胃がんではTGF-βは血管新生を抑制してがんの増殖を抑制することを見出した。またTGF-β拮抗剤とミセル型抗がん剤の併用は膵臓がんなどに有効であることを明らかにした。

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  • Lecture & Research Projects: Clinical Evaluation of Pharmaceutical care B II (2021academic year) special  - その他

  • Research Projects & Practicals: Clinical Evaluation of Pharmaceutical care C I (2021academic year) special  - その他

  • Lecture & Research Projects: Clinical Evaluation of Pharmaceutical care C I (2021academic year) special  - その他

  • Research Projects & Practicals: Clinical Evaluation of Pharmaceutical care C II (2021academic year) special  - その他

  • Lecture & Research Projects: Clinical Evaluation of Pharmaceutical care C II (2021academic year) special  - その他

  • Practical Internship (2021academic year) Year-round  - その他

  • Technical Writing and Presentation (2021academic year) Late  - その他

  • Technical Writing and Presentation (2021academic year) Late  - その他

  • Life Science 3 (2021academic year) Late  - その他

  • Introduction to clinical therapeutics (2021academic year) 1st and 2nd semester  - [第1学期]木1~2, [第2学期]木1,木2

  • Introduction to clinical therapeutics (2021academic year) 1st and 2nd semester  - [第1学期]木1~2, [第2学期]木1,木2

  • Introduction to clinical sciences (2021academic year) Summer concentration  - その他

  • Practice in Fundamental Pharmaceutical Sciences III (2021academic year) Second semester  - その他6~9

  • Practice in Fundamental Pharmaceutical Sciences III (2021academic year) Second semester  - その他6~9

  • Practice in Fundamental Pharmaceutical Sciences III (2021academic year) Second semester  - その他6~9

  • Practice in Fundamental Pharmaceutical Sciences III (2021academic year) Second semester  - その他6~9

  • Pharmacotherapeutic 1 (2021academic year) 1st semester  - 水1~2

  • Pharmacotherapeutic 1 (2021academic year) 1st semester  - 水1~2

  • Pharmacotherapeutic 2 (2021academic year) Second semester  - 水1~2

  • Pharmacotherapeutic 2 (2021academic year) Second semester  - 水1~2

  • Pharmacotherapeutic 3 (2021academic year) 1st semester  - 水3~4

  • Pharmacotherapeutic 3 (2021academic year) 1st semester  - 水3~4

  • Pharmacotherapeutic 4 (2021academic year) Second semester  - 水3~4

  • Pharmacotherapeutic 4 (2021academic year) Second semester  - 水3~4

  • Scientific investigation of human beings (2020academic year) Third semester  - 月1,月2

  • Introduction to Human Care Innovation and Health Care (2020academic year) Prophase  - 金5,金6

  • Big Data (2020academic year) Late  - 水1,水2

  • Advanced Internship for Interdisciplinary Medical Sciences and Engineering (2020academic year) Year-round  - その他

  • Internship for Interdisciplinary Medical Sciences and Engineering (2020academic year) Year-round  - その他

  • Technical English for Interdisciplinary Medical Sciences and Engineering (2020academic year) Late  - その他

  • Exercises for Interdisciplinary Medical Sciences and Engineering (2020academic year) Late  - その他

  • Research Works for Interdisciplinary Medical Sciences and Engineering (2020academic year) Year-round  - その他

  • Advanced Interdisciplinary Medical Sciences and Engineering (2020academic year) Prophase  - その他

  • General Exercises for Interdisciplinary Medical Sciences and Engineering (2020academic year) Late  - その他

  • Applying medical sciences and technologies to clinical practice (2020academic year) Late  - その他

  • Pharmaceutical Biomedicine (2020academic year) special  - その他

  • Research Projects & Practicals: Clinical Evaluation of Pharmaceutical care A I (2020academic year) special  - その他

  • Lecture & Research Projects: Clinical Evaluation of Pharmaceutical care A I (2020academic year) special  - その他

  • Research Projects & Practicals: Clinical Evaluation of Pharmaceutical care A II (2020academic year) special  - その他

  • Lecture & Research Projects: Clinical Evaluation of Pharmaceutical care A II (2020academic year) special  - その他

  • Research Projects & Practicals: Clinical Evaluation of Pharmaceutical care B I (2020academic year) special  - その他

  • Lecture & Research Projects: Clinical Evaluation of Pharmaceutical care B I (2020academic year) special  - その他

  • Research Projects & Practicals: Clinical Evaluation of Pharmaceutical care B II (2020academic year) special  - その他

  • Lecture & Research Projects: Clinical Evaluation of Pharmaceutical care B II (2020academic year) special  - その他

  • Research Projects & Practicals: Clinical Evaluation of Pharmaceutical care C I (2020academic year) special  - その他

  • Lecture & Research Projects: Clinical Evaluation of Pharmaceutical care C I (2020academic year) special  - その他

  • Research Projects & Practicals: Clinical Evaluation of Pharmaceutical care C II (2020academic year) special  - その他

  • Lecture & Research Projects: Clinical Evaluation of Pharmaceutical care C II (2020academic year) special  - その他

  • Practical Internship (2020academic year) Year-round  - その他

  • Practical Interdisciplinary Medical Sciences and Engineering (2020academic year) Late  - その他

  • Technical Writing and Presentation (2020academic year) Late  - その他

  • Life Science 3 (2020academic year) special  - その他

  • Introduction to clinical therapeutics (2020academic year) 1st and 2nd semester  - 木1,木2

  • Introduction to clinical sciences (2020academic year) Summer concentration  - その他

  • Practice in Fundamental Pharmaceutical Sciences III (2020academic year) Second semester  - その他

  • Practice in Fundamental Pharmaceutical Sciences III (2020academic year) Second semester  - その他

  • Pharmacotherapeutic 1 (2020academic year) 1st semester  - 水1,水2

  • Pharmacotherapeutic 1 (2020academic year) 1st semester  - 水1,水2

  • Pharmacotherapeutic 2 (2020academic year) Second semester  - 水1,水2

  • Pharmacotherapeutic 2 (2020academic year) Second semester  - 水1,水2

  • Pharmacotherapeutic 3 (2020academic year) 1st semester  - 水3,水4

  • Pharmacotherapeutic 3 (2020academic year) 1st semester  - 水3,水4

  • Pharmacotherapeutic 4 (2020academic year) Second semester  - 水3,水4

  • Pharmacotherapeutic 4 (2020academic year) Second semester  - 水3,水4

  • Pharmacotherapeutic I (2020academic year) 1st and 2nd semester  - 水1,水2

  • Pharmacotherapeutic II (2020academic year) 1st and 2nd semester  - 水3,水4

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