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Comprehensive study on precise diagnosis and new chemotherapy for micrometastatic lymph nodes

Research Project

Project/Area Number 18H03544
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 90130:Medical systems-related
Research InstitutionTohoku University

Principal Investigator

SAKAMOTO Maya  東北大学, 歯学研究科, 大学院非常勤講師 (90157686)

Co-Investigator(Kenkyū-buntansha) 小玉 哲也  東北大学, 医工学研究科, 教授 (40271986)
宮澤 正顯  近畿大学, 医学部, 教授 (60167757)
伊藤 康一  東北大学, 情報科学研究科, 准教授 (70400299)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywordsリンパ節転移 / 精密診断 / 化学療法 / 超音波 / 早期診断 / リンパ行性薬剤送達法
Outline of Final Research Achievements

In order to develop a precise diagnostic imaging method and minimally invasive local chemotherapy using lymphatic drug delivery system (LDDS) for early metastatic lymph nodes, we conducted experiments using a mouse model of lymph node metastasis.
The results showed that lymphatic sinus contrast imaging using micro-CT was useful as an imaging method for the diagnosis of metastatic lymph nodes in the clinical N0 state, because tumor cells proliferating in the lymphatic sinus blocked the flow of contrast medium from upstream lymph nodes, indicating a focal defect of contrast medium. We also found that the optimal infusion rate of drugs into upstream lymph nodes using LDDS was 10-80 μL/min, and that administration of anticancer agents using LDDS had an antitumor effect on metastatic lymph nodes in the model of clinical N0 stage.

Academic Significance and Societal Importance of the Research Achievements

リンパ節転移の有無は,患者の生命予後に大きく関与する.しかし,腫大する前の臨床的N0状態の初期のリンパ節転移を高精度に診断できる画像診断法は確立されていない.また,転移初期のリンパ節では腫瘍新生血管が形成されず, EPR効果にもとづく高分子薬剤治療の効果が期待できないことなどから,全身化学療法の奏効率には限界がある.
本研究は,転移初期段階のリンパ節を対象とした高精度な画像診断法,およびリンパ行性薬剤送達法(LDDS)を用いた新規化学療法の開発を目的とする.低侵襲,低コスト,奏効性の高い転移リンパ節治療が期待でき,高齢者や有病者,あるいは経済的に困窮している世界中のがん患者の救済に繋がる.

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (38 results)

All 2021 2020 2019 2018

All Journal Article (14 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 14 results,  Open Access: 12 results) Presentation (24 results) (of which Int'l Joint Research: 4 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
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High detection sensitivity and reliable morphological correlation of PET with a silicon photomultiplier for primary tongue squamous cell carcinoma2020

    • Author(s)
      Kojima I, Takanami K, Ogawa T, Sakamoto M, Nagai H, Miyashita H, Iikubo M.
    • Journal Title

      Ann Nucl Med

      Volume: 34 Issue: 9 Pages: 643-352

    • DOI

      10.1007/s12149-020-01489-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical utility of apparent diffusion coefficient and diffusion-weighted magnetic resonance imaging for resectability assessment of head and neck tumors with skull base invasion2020

    • Author(s)
      Ogawa T, Kojima I, Wakamori S, Yoshida T, Murata T, Sakamoto M, Ohkoshi A, Nakanome A, Endo H, Endo T, Usubuchi H, Katori Y.
    • Journal Title

      Head Neck

      Volume: 42 Issue: 10 Pages: 2896-2904

    • DOI

      10.1002/hed.26336

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of tumor vascularization in a mouse model of metastatic lung cancer2019

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

      Sci Rep.

      Volume: 9 Pages: 16029-16029

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Use of a lymphatic drug delivery system and sonoporation to target malignant metastatic breast cancer cells proliferating in the marginal sinuses2019

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

      Scientific Reports.

      Volume: 9 Pages: 13242-13242

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Annual Research 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
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Superselective Drug Delivery Using Doxorubicin-Encapsulated Liposomes and Ultrasound in a Mouse Model of Lung Metastasis Activation2018

    • Author(s)
      Ouchi Tomoki、Sukhbaatar Ariunbuyan、Horie Sachiko、Sakamoto Maya、Shiga Kiyoto、Mori Shiro、Kodama Tetsuya
    • Journal Title

      Ultrasound in Medicine & Biology

      Volume: 44 Issue: 8 Pages: 1818-1827

    • DOI

      10.1016/j.ultrasmedbio.2018.04.003

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tumor cell invasion from the marginal sinus into extranodal veins during early-stage lymph node metastasis can be a starting point for hematogenous metastasis2018

    • Author(s)
      Kodama Tetsuya、Mori Shiro、Nose Masato
    • Journal Title

      Journal of Cancer Metastasis and Treatment

      Volume: 4 Issue: 11 Pages: 56-56

    • DOI

      10.20517/2394-4722.2018.61

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical utility of dynamic-enhanced MRI in salivary gland tumors: retrospective study and literature review.2018

    • Author(s)
      Ogawa T, Kojima I, Ishii R, Sakamoto M, Murata T, Suzuki T, Kato K, Nakanome A, Ohkoshi A, Ishida E, Kakehata S, Shiga K, Katori Y.
    • Journal Title

      Eur Arch Otorhinolaryngol.

      Volume: 印刷中 Issue: 6 Pages: 1613-1621

    • DOI

      10.1007/s00405-018-4965-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Lymph node metastasis mouse model and its treatment.2020

    • 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 system.2020

    • 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 System.2020

    • 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] 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] Improvement of chemotherapy for the lymph node metastasis.2020

    • 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 system.2020

    • 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] 半導体検出器を搭載した新PET装置による舌がん原発腫瘍の検出能および腫瘍サイズとの相関に関する検討2020

    • Author(s)
      小嶋郁穂、阪本真弥、飯久保正弘.
    • Organizer
      第33回日本口腔診断学会・第30回日本口腔内科学会・第13回日本口腔検査学会合同学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 半導体検出器を搭載した新PET装置による口腔がんリンパ節転移の診断精度2019

    • Author(s)
      小嶋郁穂、高浪健太郎、小川武則、外山由貴、齋藤美穂子、阪本真弥、飯久保正弘、髙橋 哲
    • Organizer
      日本歯科放射線学会第60回学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Flow dynamics of lymphatic drug delivery system in in mice.2019

    • 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 Annual Research Report
  • [Presentation] Efficacy of the positron emission tomography scanner with semiconductor photomultiplier in diagnosis of lymph node metastases in oral cancer2019

    • Author(s)
      Kojima I, Iikubo M, Nishioka T, Sakamoto M
    • Organizer
      22th International Congress of Dental and Maxillofacial Radiology
    • Related Report
      2019 Annual Research 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 Annual Research Report
  • [Presentation] Importance of osmotic pressure for lymphatic drug delivery system.2019

    • 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 Annual Research Report
  • [Presentation] 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 Annual Research Report
  • [Presentation] メソトレキセートを用いたリンパ行性薬剤送達法によるリンパ節転移の治療.2018

    • Author(s)
      石橋亮太,伹野晃介,和室昂佑,森士朗,小玉哲也.
    • Organizer
      日本機械学会 第31回バイオエンジニアリング講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 転移リンパ節に対するニムスチンを用いたリンパ行性薬剤送達法に関する研究.2018

    • Author(s)
      伹野晃介,石橋亮太,和室昂佑,森士朗,小玉哲也.
    • Organizer
      日本機械学会 第31回バイオエンジニアリング講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 口腔癌頸部リンパ節転移の節外進展診断における3 テスラblack-blood MR imaging法の有用性.2018

    • Author(s)
      阪本真弥,小嶋郁穂,飯久保正弘,西岡貴志,笹野高嗣,伊藤康一,青木孝文,小川武則,森士朗,小玉哲也.
    • Organizer
      日本歯科放射線学会第59回学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 半導体検出器を搭載した新PET装置による舌がん原発腫瘍の検出能の検討2018

    • Author(s)
      小嶋郁穂、阪本真弥、飯久保正弘、高浪健太郎、外山由貴、古内 壽、小川武則、永井宏和、宮下 仁、髙橋 哲
    • Organizer
      第23回日本歯科放射線学会臨床画像大会
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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