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Anti-angiogenic and lymphangiogenic therapy improves the tumor microenvironment and enhances the effectiveness of immunotherapy

Research Project

Project/Area Number 18K08133
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionTohoku University

Principal Investigator

Okazaki Tatsuma  東北大学, 大学病院, 講師 (40396479)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsリンパ管 / がん免疫療法 / 血管 / 癌微小環境 / 腫瘍 / 壁側胸膜 / リンパ管新生阻害 / 血管新生阻害 / 免疫療法 / 抗腫瘍免疫療法 / 抗脈管療法 / 抗血管新生療法 / 抗リンパ管新生療法
Outline of Final Research Achievements

In this study, we identified a previously unknown normal anatomy of lymphatics and blood vessels in the pleura covering the mouse chest wall and diaphragm. We immuno-stained the chest wall and diaphragm with markers for lymphatics and blood vessels. We observed and identified and their anatomy using a microscope.
Lymphatics include initial and collecting lymphatics. We identified their distribution in the pleura. We also confirmed the distribution of blood vessel networks of arteries, veins, and capillaries in the pleura. Next, we developed a disseminated metastatic mouse tumor model on the pleura of the chest wall and diaphragm. We immuno-stained this model with lymphatic and blood vessel markers. We were able to clearly observe the flowing out lymphatics and flowing in blood vessels of each tumor using a microscope. In this model, each tumor was small, and lymphangiogenesis and angiogenesis from the surrounding vasculatures to the tumor could be identified.

Academic Significance and Societal Importance of the Research Achievements

癌や肺炎等の合併症に胸水貯留がある。胸水は肺を圧排し呼吸苦等を引き起こし患者さんの予後を悪化させる。胸水は胸膜の血管から産生されリンパ管から排出される。しかし、胸膜のリンパ管や血管の正常解剖、及び癌による病理学的変化はこれまで不明だった。本研究はこれらの不明な点を同定し、新規胸水対策の可能性を示した。また、本腫瘍モデルでは明瞭に脈管系を観察できるため、免疫細胞の腫瘍リンパ管や血管への分布を観察できる。癌免疫療法の効果を確認する際に、本モデルは腫瘍と脈管における免疫細胞の分布の確認を可能とした。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (27 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 6 results) Presentation (12 results) (of which Int'l Joint Research: 1 results,  Invited: 8 results) Book (2 results)

  • [Int'l Joint Research] Tianjin Medical University(中国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Frequent Onsets of Cellulitis in Lower Limbs with Lymphedema Following COVID-19 mRNA Vaccination2022

    • Author(s)
      51.Okazaki, T., Matashiro, M., Kodama, G., Tshubota, T., Furusawa, Y., and Izumi, S.
    • Journal Title

      Vaccines

      Volume: 10 Issue: 4 Pages: 517-517

    • DOI

      10.3390/vaccines10040517

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characteristics of aspiration pneumonia patients in acute care hospitals: A multicenter, retrospective survey in Northern Japan2021

    • Author(s)
      1.Suzuki J, Okazaki T, Katori Y., et al.,
    • Journal Title

      PLos One

      Volume: 16(7) Issue: 7 Pages: e0254261-e0254261

    • DOI

      10.1371/journal.pone.0254261

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Respiratory Muscle Weakness as a Risk Factor for Pneumonia in Older People2021

    • Author(s)
      Okazaki Tatsuma、Suzukamo Yoshimi、Miyatake Midori、Komatsu Riyo、Yaekashiwa Masahiro、Nihei Mayumi、Izumi Shinichi、Ebihara Takae
    • Journal Title

      Gerontology

      Volume: Feb 23 Issue: 5 Pages: 1-10

    • DOI

      10.1159/000514007

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Questionnaire survey on pharyngolaryngeal sensation evaluation regarding dysphagia in Japan2021

    • Author(s)
      Kambayashi Tomonori、Kato Kengo、Ikeda Ryoukichi、Suzuki Jun、Honkura Yohei、Hirano-Kawamoto Ai、Ohta Jun、Kagaya Hitoshi、Inoue Makoto、Hyodo Masamitsu、Omori Koichi、Suehiro Atsushi、Okazaki Tatsuma、Izumi Shin-Ichi、Katori Yukio
    • Journal Title

      Auris Nasus Larynx

      Volume: Feb14 Issue: 4 Pages: 41-49

    • DOI

      10.1016/j.anl.2021.01.022

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 2.Association between sarcopenia and pneumonia in older people.2020

    • Author(s)
      Okazaki T, Ebihara S, Mori T, Izumi S, Ebihara T.
    • Journal Title

      Geriatr Gerontol Int.

      Volume: 20(1) Issue: 1 Pages: 7-13

    • DOI

      10.1111/ggi.13839

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 1.Ultrasonography to detect age-related changes in swallowing muscles2019

    • Author(s)
      Takashi Mori, Shinichi Izumi,Y oshimi Suzukamo, Tatsuma Okazaki, Susumu Iketani
    • Journal Title

      European Geriatric Medicine

      Volume: 10(5) Pages: 753-760

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 誤嚥性肺炎防止の知恵2019

    • Author(s)
      1.岡崎達馬、出江紳一
    • Journal Title

      日本脳卒中協会会報 JSA News

      Volume: 56 Pages: 2-2

    • Related Report
      2018 Research-status Report
  • [Journal Article] 嚥下障害症例における呼吸機能訓練の役割2019

    • Author(s)
      2.岡崎達馬、黒澤一、出江伸一
    • Journal Title

      JOHNS

      Volume: 35 Pages: 365367-365367

    • Related Report
      2018 Research-status Report
  • [Journal Article] Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor52018

    • Author(s)
      Yoko Tsukita, Tatsuma Okazaki, Satoru Ebihara, Riyo Komatsu, Mayumi Nihei, Makoto Kobayashi, Taizou Hirano, Hisatoshi Sugiura, Tsutomu Tamada, Nobuyuki Tanaka, Yasufumi Sato, Hideo Yagita, Masakazu Ichinose
    • Journal Title

      OncoImmunology.

      Volume: 8(2) Issue: 2 Pages: 1543526-1543526

    • DOI

      10.1080/2162402x.2018.1543526

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aspiration pneumonia induces muscle atrophy in the respiratory, skeletal, and swallowing systems.2018

    • Author(s)
      Riyo Komatsu, Tatsuma Okazaki, Satoru Ebihara, Makoto Kobayashi, Yoko Tsukita, Mayumi Nihei, Hisatoshi Sugiura, Kaijun Niu, Takae Ebihara, Masakazu Ichinose.
    • Journal Title

      Journal of Cachexia, Sarcopenia and Muscle.

      Volume: 9(4) Issue: 4 Pages: 643653-643653

    • DOI

      10.1002/jcsm.12297

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Physical inactivity is associated with decreased growth differentiation factor 11 in chronic obstructive pulmonary disease2018

    • Author(s)
      Rie Tanaka, Hisatoshi Sugiura, Mitsuhiro Yamada, Tomohiro Ichikawa, Akira Koarai, Naoya Fujino, Satoru Yanagisawa, Katsuhiro Onodera, Tadahisa Numakura, Kei Sato, Yorihiko Kyogoku, Hirohito Sano, Shun Yamanaka, Tatsuma Okazaki, Tsutomu Tamada, Motohiko Miura, Tsuneyuki Takahashi, Masakazu Ichinose
    • Journal Title

      Int J Chron Obstruct Pulmon Dis.

      Volume: 13 Pages: 1333-1342

    • DOI

      10.2147/copd.s157035

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 呼吸器疾患とサルコペニア・フレイル2018

    • Author(s)
      海老原 覚、 岡崎達馬
    • Journal Title

      日本内科学会雑誌

      Volume: 107(9) Pages: 1708-1712

    • Related Report
      2018 Research-status Report
  • [Presentation] 高齢者肺炎のサルコペニア とリハビリテーション医療2022

    • Author(s)
      岡崎達馬
    • Organizer
      第5回日本リハビリテーション医学会秋季学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 誤嚥性肺炎とサルコペニア の関係2022

    • Author(s)
      岡崎達馬
    • Organizer
      第63回日本老年医学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] サルコペニア 、嚥下障害、誤嚥生肺炎をめぐる最新の知見2022

    • Author(s)
      岡崎達馬
    • Organizer
      第58回日本リハビリテーション医学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 呼吸筋のサルコペニアと低栄養は高齢者肺炎発症と再発の危険因子である~横断コホート研究~2020

    • Author(s)
      岡崎達馬 鈴鴨よしみ 宮武ミドリ 八重柏政宏 二瓶真由美 出江紳一  海老原孝枝
    • Organizer
      日本呼吸器学会
    • Related Report
      2020 Research-status Report
  • [Presentation] サルコペニアと高齢者肺炎2020

    • Author(s)
      岡崎達馬 鈴鴨よしみ 森隆行 出江紳一
    • Organizer
      日本臨床医療福祉学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 炎症とサルコペニア~高齢者肺炎との関係を中心に~2020

    • Author(s)
      岡崎達馬
    • Organizer
      日本リハビリテーション栄養学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Sarcopenia in respiratory muscles and malnutrition induce onset and relapse of pneumonia in aged people2020

    • Author(s)
      Tatsuma Okazaki, Midori Miyatake, Yoshimi Suzukamo, Shinichi Izumi, Koichi Kozaki, Takae Ebihara
    • Organizer
      International Conference on Frailty and Sarcopenia Research
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 1.高齢者誤嚥性肺炎へのサルコペニアの関与2019

    • Author(s)
      岡崎達馬 海老原孝枝 永井久美子 庄司真美 小松理世 八重柏政宏 二瓶真由美 出江伸一
    • Organizer
      日本老年医学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 誤嚥性肺炎発症へのサルコペニアの関与2019

    • Author(s)
      岡崎達馬 海老原孝枝 永井久美子 庄司真美 小松理世 八重柏政宏 二瓶真由美 出江伸一
    • Organizer
      日本リハビリテーション医学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 高齢者筋萎縮、低栄養、嚥下障害の現状と課題 超高齢者社会における医療の取り組みーロコモ・フレイル・サルコペニア2019

    • Author(s)
      出江伸一, 岡崎達馬
    • Organizer
      日本医学会シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 超高齢化社会における sarcopenic dysphasia について ~嚥下関連肺炎との関係~2019

    • Author(s)
      岡崎達馬
    • Organizer
      日本摂食嚥下リハビリテーション学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 嚥下障害関連肺炎とサルコペニア及びマイオカインの関係2019

    • Author(s)
      岡崎達馬
    • Organizer
      日本頭頸部外科学会総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Book] 内部障害のリハビリテーション医学・医療テキスト2022

    • Author(s)
      海老原覚 岡崎達馬
    • Total Pages
      275
    • Publisher
      医学書院
    • ISBN
      9784260045919
    • Related Report
      2021 Annual Research Report
  • [Book] 呼吸器系と健康長寿・フレイル対策2020

    • Author(s)
      岡崎達馬他
    • Total Pages
      136
    • Publisher
      先端医学社
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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