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An experimental study on the theory of lymph node-mediated hematogenous metastasis

Research Project

Project/Area Number 19K22941
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 90:Biomedical engineering and related fields
Research InstitutionTohoku University

Principal Investigator

KODAMA Tetsuya  東北大学, 医工学研究科, 教授 (40271986)

Co-Investigator(Kenkyū-buntansha) 山口 匡  千葉大学, フロンティア医工学センター, 教授 (40334172)
Project Period (FY) 2019-06-28 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywordsリンパ節転移 / 転移 / 解剖 / 血流欠損 / 転移理論 / リンパ節 / 全身転移 / センチネルリンパ節 / 遠隔転移 / 血行性
Outline of Research at the Start

本研究では, リンパ節介在血行性転移理論の実験的検証を目的とする.この理論では, 腫瘍細胞が輸入リンパ管からリンパ節の辺縁洞に侵入する段階において, 辺縁洞を貫通する静脈に浸潤し, 腫瘍細胞は血行性として遠隔臓器に転移するものと考える. 実験では, リンパ節腫脹マウスを用いて, リンパ節に転移を誘導し, この転移を来たしたリンパ節内の腫瘍細胞の動態を3D蛍光顕微解析および病理像で解析する.

Outline of Final Research Achievements

This proposal is to experimentally verify the theory of lymph node-mediated hematogenous metastasis, which considers that the sentinel lymph node can be the origin of systemic metastasis. The results of this study can be summarized in the following two points. (1) A perfusion defect is formed in the early stage of lymph node metastasis. (2) The pathological images of lymph nodes in patients with head and neck cancer were carefully examined, and the presence of perforating branches penetrating the lymph node capsule was confirmed. The lymph node-mediated hematogenous metastasis theory accurately describes hematogenous metastasis in the early stage when tumor cells have metastasized and proliferated in the marginal sinuses of lymph nodes. In the future, it is necessary to accumulate experimental evidence for this theory.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は, 本理論が適用される転移リンパ節のステージを明らかにした. 本理論に基づきセンチネルリンパ節からの遠隔転移を予防するには, 原発巣が確認された段階で, 原発巣周囲に確認される全てのリンパ節に対して予防的治療を実施することが求められる. 本研究成果は, 本理論の学術的根拠ならびに転移初期段階にあるリンパ節の予防的治療の理論的根拠を提示するものである.

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (37 results)

All 2021 2020 2019 Other

All Journal Article (9 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Open Access: 9 results) Presentation (26 results) (of which Int'l Joint Research: 10 results,  Invited: 1 results) Remarks (2 results)

  • [Journal Article] Study of the physicochemical properties of drugs suitable for administration using a lymphatic drug delivery system2021

    • Author(s)
      Fukumura Ryoichi、Sukhbaatar Ariunbuyan、Mishra Radhika、Sakamoto Maya、Mori Shiro、Kodama Tetsuya
    • Journal Title

      Cancer Science

      Volume: - Issue: 5 Pages: 1-11

    • DOI

      10.1111/cas.14867

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optimization of the delivery of molecules into lymph nodes using a lymphatic drug delivery system with ultrasound2021

    • Author(s)
      Kato Shigeki、Yoshiba Shota、Mori Shiro、Kodama Tetsuya
    • Journal Title

      International Journal of Pharmaceutics

      Volume: 597 Pages: 120324-120324

    • DOI

      10.1016/j.ijpharm.2021.120324

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intranodal pressure of a metastatic lymph node reflects the response to lymphatic drug delivery system2020

    • Author(s)
      Kato Shigeki、Takeda Kazu、Sukhbaatar Ariunbuyan、Sakamoto Maya、Mori Shiro、Shiga Kiyoto、Kodama Tetsuya
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 11 Pages: 4232-4241

    • DOI

      10.1111/cas.14640

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo delivery of an exogenous molecule into murine T lymphocytes using a lymphatic drug delivery system combined with sonoporation.2020

    • Author(s)
      Kato S, Shirai Y, Motozono C, Kanzaki H, Mori S, Kodama T
    • Journal Title

      Biochem Biophys Res Commun

      Volume: - Issue: 4 Pages: 1025-1031

    • DOI

      10.1016/j.bbrc.2020.02.174

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of tumor vascularization in a mouse model of metastatic lung cancer.2019

    • Author(s)
      Sukhbaatar A, Sakamoto M, Mori S, Kodama T.
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 16029-16029

    • DOI

      10.1038/s41598-019-52144-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Use of a lymphatic drug delivery system and sonoporation to target malignant metastatic breast cancer cells proliferating in the marginal sinuses.2019

    • Author(s)
      Kato S, Shirai Y, Sakamoto M, Mori S, Kodama T
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 13242-13242

    • DOI

      10.1038/s41598-019-49386-5

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A model system for studying superselective radiotherapy of lymph node metastasis in mice with swollen lymph nodes2019

    • Author(s)
      Kikuchi R, Sukhbaatar A, Sakamoto M, Mori S, Kodama T
    • Journal Title

      Clin Transl Radiat Oncol

      Volume: 20 Pages: 53-57

    • DOI

      10.1016/j.ctro.2019.05.002

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Treatment of false‐negative metastatic lymph nodes by a lymphatic drug delivery system with 5‐fluorouracil2019

    • Author(s)
      Fujii Honoka、Horie Sachiko、Sukhbaatar Ariunbuyan、Mishra Radhika、Sakamoto Maya、Mori Shiro、Kodama Tetsuya
    • Journal Title

      Cancer Medicine

      Volume: 印刷中 Issue: 5 Pages: 2241-2251

    • DOI

      10.1002/cam4.2125

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Imaging of the Mouse Lymphatic Sinus during Early Stage Lymph Node Metastasis Using Intranodal Lymphangiography with X-ray Micro-computed Tomography2019

    • Author(s)
      Iwamura Ryo、Sakamoto Maya、Mori Shiro、Kodama Tetsuya
    • Journal Title

      Molecular Imaging and Biology

      Volume: 印刷中 Issue: 5 Pages: 825-834

    • DOI

      10.1007/s11307-018-01303-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Lymph node metastasis mouse model and its treatment2020

    • Author(s)
      S Ariunbuyan, Sakamoto M, Mori S, Kodama T
    • Organizer
      International Joint Symposium 2020(The 15th International Workshop on Biomaterials in Interface Science, The 11th Symposium on Innovative Dental-Engineering Alliance (IDEA))
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Imaging of the mouse lymphatic sinus during lymphatic administration of high osmotic pressure solutions using a contrast-enhanced high-frequency ultrasound imaging system2020

    • Author(s)
      Fukumura R, Mishra R, S Ariunbuyan, Mori S, Kodama T
    • Organizer
      World Molecular Imaging Congress (WMIC) virtual 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Optimized fluid parameters for enhanced treatment efficacy for drug delivery using the Lymphatic Drug Delivery System2020

    • Author(s)
      Mishra R, Fukumura R, S Ariunbuyan, Mori S, Kodama T
    • Organizer
      World Molecular Imaging Congress (WMIC) virtual 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Does radiotherapy metastatic lymph nodes induce an abscopal effect?2020

    • Author(s)
      Sora S, S Ariunbuyan, Sakamoto M, Mori S, Kodama T
    • Organizer
      World Molecular Imaging Congress (WMIC) virtual 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 浸透圧にともなうリンパ節の形態変化に関する研究2020

    • Author(s)
      福村凌一,Radhika Mishra, Ariunbuyan Sukhbaatar, 森士朗,小玉哲也
    • Organizer
      日本超音波医学会第93回学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Improvement of chemotherapy for the lymph node metastasis2020

    • Author(s)
      S Ariunbuyan,Kodama T, Mori S
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Importance of drug osmotic pressure and viscosity for enhancing treatment effect using lymphatic drug delivery system2020

    • Author(s)
      Mishra R, Fukumura R, S Ariunbuyan, Mori S, Kodama T
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] マウスの転移リンパ節治療における超選択的放射線治療2020

    • Author(s)
      空翔太,スフバートル アリウンブヤン,森士朗,小玉哲也
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 複数の転移リンパ節モデルマウスの開発2020

    • Author(s)
      永松大輝,アリウンブヤン スフバートル,ラディカ ミシュラ,森士朗,小玉哲也
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] リンパ行性薬物送達法におけるリンパ節への分子集積の定量解析2020

    • Author(s)
      鈴木健大,アリウンブヤン スフバートル,森士朗,伊藤明宏,小玉哲也
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] リンパ行性薬剤送達法を用いた抗がん剤投与時における浸透圧の治療依存性2020

    • Author(s)
      福村凌一,ミシュラ ラディカ,スフバートル アリウンブヤン,永松大輝,森士朗,小玉哲也
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] リンパ行性薬剤送達法における薬剤浸透圧変化にともなう転移リンパ節の治療評価に関する研究2020

    • Author(s)
      福村凌一,Radhika Mishra,Ariunbuyan Sukhbaatar,森士朗,小玉哲也
    • Organizer
      日本超音波医学会第60回東北地方会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 深層学習を用いた乳癌造影超音波定量解析における客観的病変範囲評価2020

    • Author(s)
      樋口賢一, 森菜緒子, 伊藤康一, 小玉哲也, 高瀬圭
    • Organizer
      日本超音波医学会第93回学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] リンパ節転移モデルマウスの3次元in vivo超音波定量評価の基礎検討2020

    • Author(s)
      大村眞朗, 永松大輝, 小玉哲也, 佐藤悠佑, 吉田憲司, 山口匡
    • Organizer
      日本超音波医学会第93回学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Effect of drug osmotic pressure on the delivery efficiency for a Lymphatic Drug Delivery System2019

    • Author(s)
      Fukumura R, Mishra R, Sukhbaatar A, Mori S, Kodama T
    • Organizer
      Tohoku University Forum for Creativity Thematic 2019, Cancer - from Biology to Acceptance
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Enhancement of Epirubicin Anticancer Activity by LDDS in Metastatic Lymph Node Mouse Model2019

    • Author(s)
      Sukhbaatar A, Mori S, Kodama T
    • Organizer
      16th International Conference on Flow Dynamics
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Optimized Physiochemical Properties for Lymphatic Drug Delivery System2019

    • Author(s)
      Fukumura R, Mishra R, Sukhbaatar A, Yadav N, Shrivastava S, Saurav S, Shiga K, Mori S, Kodama T
    • Organizer
      16th International Conference on Flow Dynamics
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Flow Visualization and Lymphatic Vessel Characterization for Lymphatic Drug Delivery System2019

    • Author(s)
      Mishra R, Sukhbaatar A, Shrivastava S, Saurav S, Yadav N, Neetu K, Shiga K, Mori S, Kodama T
    • Organizer
      16th International Conference on Flow Dynamics
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effect of Osmotic Pressure of drug on treatment efficacy for a Lymphatic Drug Delivery System2019

    • Author(s)
      Mishra R, Sukhbaatar A, Mori S, Kodama T
    • Organizer
      The 4th International Symposium on Creation of Life Innovation Materials for Interdisciplinary and International Researcher Development(iLIM-4)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effect of drug osmotic pressure on the therapeutic effect using a lymphatic drug delivery system2019

    • Author(s)
      Fukumura R, Mishra R, Sukhbaatar A, Mori S, Kodama T
    • Organizer
      The 4th International Symposium on Creation of Life Innovation Materials for Interdisciplinary and International Researcher Development(iLIM-4)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] リンパ行性薬物送達法に関する研究2019

    • Author(s)
      小玉哲也
    • Organizer
      第41回生体膜と薬物の相互作用シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Removal of lymph nodes increases the incidence of metastasis2019

    • Author(s)
      Ariunbuyan S, Takahashi T, Mori S, Kodama T
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] リンパ系薬物送達システムに必要な薬物の浸透圧と粘度の最適範囲2019

    • Author(s)
      福村凌一,ラディカ ミシュラ,アリウンブヤン スフバートル,阪本真弥,森士朗,志賀清人,小玉哲也
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Importance of osmotic pressure for lymphatic drug delivery system2019

    • Author(s)
      Mishra R, Fukumura R, Ariunbuyan S, Sakamoto M, Mori S, Shiga K, Kodama T
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Therapeutic effect of epirubicin at different osmotic pressure in metastatic lymph nodes at the early stage using lymphatic drug delivery system2019

    • Author(s)
      Sukhbaatar Ariunbuyan, 森士朗,小玉哲也
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Flow dynamics of lymphatic drug delivery system in in mice2019

    • Author(s)
      Mishra Radhika, Sukhbaatar Ariunbuyan, 阪本真弥,森士朗,小玉哲也
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Research-status Report
  • [Remarks] 小玉研究室ホームページ

    • URL

      https://web.tohoku.ac.jp/kodama/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 小玉研究室ホームページ

    • URL

      https://web.tohoku.ac.jp/kodama/achievement/

    • Related Report
      2019 Research-status Report

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Published: 2019-07-04   Modified: 2022-01-27  

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