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AIM expression, mutation and function in canine histiocytic sarcoma

Research Project

Project/Area Number 18H02340
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 42020:Veterinary medical science-related
Research InstitutionThe University of Tokyo

Principal Investigator

Yonezawa Tomohiro  東京大学, 大学院農学生命科学研究科(農学部), 准教授 (10433715)

Co-Investigator(Kenkyū-buntansha) 盆子原 誠  日本獣医生命科学大学, 獣医学部, 教授 (50343611)
角田 茂  東京大学, 大学院農学生命科学研究科(農学部), 准教授 (80345032)
前田 真吾  東京大学, 大学院農学生命科学研究科(農学部), 助教 (80755546)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Keywords組織球 / アポトーシス / 腫瘍 / AIM / macrophage / 病態 / 内科 / 免疫
Outline of Final Research Achievements

The molecular pathogenesis of canine histiocytic sarcoma remains unclear. In this study, the relationship of AIM, apoptosis inhibitor of macrophage to this disease was investigated. When recombinant canine AIM was added to the media of canine histiocytic sarcoma cell line, the cell number decreased dose-dependently via apoptosis. When AIM overexpressed cell line was transferred to the nude mice, the tumor growth speed was significantly lower. The AIM genes of the patients had missense mutations with high probability. These results suggest that AIM intrinsically induce the apoptosis of histiocytes in dogs and AIM gene mutation could be one of the triggers of histiocytic sarcoma progression.

Academic Significance and Societal Importance of the Research Achievements

これまでAIMの脂質代謝、肝硬変、腎不全との関連については活発に研究されてきたが、マクロファージや組織球に関わる研究はいわば盲点になっていた。応募者は獣医学的な視点からAIM研究に取り組んだため、定説の盲点をついた仮説にいち早く到達し、独自性のある研究を展開できた。また、マクロファージと腫瘍といえば、腫瘍関連性マクロファージ(TAM)がよく知られている。TAMの分化制御機構は明らかになっておらず、また臨床例においてTAMを駆逐する方法も見つかっていない。本研究の成果はTAMの分化制御機構の解明につながることが期待される。

Report

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

Research Products

(30 results)

All 2021 2020 2019 2018

All Journal Article (16 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 16 results,  Open Access: 4 results) Presentation (14 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] BRAFV595E Mutation Associates CCL17 Expression and Regulatory T Cell Recruitment in Urothelial Carcinoma of Dogs2021

    • Author(s)
      Maeda Shingo、Yoshitake Ryohei、Chambers James K.、Uchida Kazuyuki、Eto Shotaro、Ikeda Namiko、Nakagawa Takayuki、Nishimura Ryohei、Goto-Koshino Yuko、Yonezawa Tomohiro、Momoi Yasuyuki
    • Journal Title

      Veterinary Pathology

      Volume: 18 Pages: 030098582-030098582

    • DOI

      10.1177/0300985820967449

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protease-Activated Receptor-2 Is Associated With Adverse Outcomes in Canine Mammary Carcinoma2021

    • Author(s)
      Kaji Kenjiro、Kaji Noriyuki、Hori Masatoshi、Sakai Kosei、Yonezawa Tomohiro、Maeda Shingo
    • Journal Title

      Veterinary Pathology

      Volume: 58 Pages: 53-62

    • DOI

      10.1177/0300985820963087

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isolated growth hormone deficiency in a Chihuahua with a mutation in GH1.2021

    • Author(s)
      Iio, A., Maeda, S., Yonezawa, T., Momoi, Y. and Motegi, T.
    • Journal Title

      Journal of Veterinary Diagnostic Investigation

      Volume: 32 Pages: 733-736

    • DOI

      10.1177/1040638720938671

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Expression analysis of protease-activated receptor-2 in cats2020

    • Author(s)
      Iio Aki、Kaji Kenjiro、Kaji Noriyuki、Hori Masatoshi、Yonezawa Tomohiro、Momoi Yasuyuki、Maeda Shingo
    • Journal Title

      Veterinary Immunology and Immunopathology

      Volume: 229 Pages: 110115-110115

    • DOI

      10.1016/j.vetimm.2020.110115

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Foxp3+ Regulatory T Cells Associated With CCL17/CCR4 Expression in Carcinomas of Dogs.2020

    • Author(s)
      Maeda S, Nakazawa M, Uchida M, Yoshitake R, Nakagawa T, Nishimura R, Miyamoto R, Bonkobara M, Yonezawa T, Momoi Y
    • Journal Title

      Veterinary Pathology

      Volume: 29 Pages: 1-10

    • DOI

      10.1177/0300985820921535

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ErbB2 Copy Number Aberration in Canine Urothelial Carcinoma Detected by a Digital Polymerase Chain Reaction Assay.2020

    • Author(s)
      Sakai K, Maeda S, Saeki K, Yoshitake R, Goto-Koshino Y, Nakagawa T, Nishimura R, Yonezawa T, Matsuki N
    • Journal Title

      Veterinary Pathology

      Volume: 57 Pages: 56-65

    • DOI

      10.1177/0300985819879445

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Assessment of HER2 Expression in Canine Urothelial Carcinoma of the Urinary Bladder2019

    • Author(s)
      Tsuboi Masaya、Sakai Kosei、Maeda Shingo、Chambers James K.、Yonezawa Tomohiro、Matsuki Naoaki、Uchida Kazuyuki、Nakayama Hiroyuki
    • Journal Title

      Veterinary Pathology

      Volume: 56 Pages: 369-376

    • DOI

      10.1177/0300985818817024

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Expression of apoptosis inhibitor of macrophages in tissue macrophages, leukocytes and vascular endothelial cells of dogs2019

    • Author(s)
      Uchida M.、Uchida K.、Maeda S.、Yonezawa T.
    • Journal Title

      Tissue and Cell

      Volume: 58 Pages: 112-120

    • DOI

      10.1016/j.tice.2019.05.002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CCR4 Blockade Depletes Regulatory T Cells and Prolongs Survival in a Canine Model of Bladder Cancer2019

    • Author(s)
      Shingo Maeda, Kohei Murakami, Akiko Inoue, Tomohiro Yonezawa, Naoaki Matsuki
    • Journal Title

      Cancer Immunology Research

      Volume: 7 Pages: 1175-1187

    • DOI

      10.1158/2326-6066.cir-18-0751

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Duodenal expression of antimicrobial peptides in dogs with idiopathic inflammatory bowel disease and intestinal lymphoma2019

    • Author(s)
      Nakazawa M.、Maeda S.、Omori M.、Kaji K.、Yokoyama N.、Nakagawa T.、Chambers J.K.、Uchida K.、Ohno K.、Yonezawa T.、Matsuki N.
    • Journal Title

      The Veterinary Journal

      Volume: 249 Pages: 47-52

    • DOI

      10.1016/j.tvjl.2019.05.006

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sphingosine-1-phosphate (S1P) signaling regulates the production of intestinal IgA and its potential role in the pathogenesis of canine inflammatory bowel disease2019

    • Author(s)
      NAKAZAWA Maho、MAEDA Shingo、YOKOYAMA Nozomu、NAKAGAWA Taisuke、YONEZAWA Tomohiro、OHNO Koichi、MATSUKI Naoaki
    • Journal Title

      J. Vet. Med. Sci.

      Volume: 81 Issue: 9 Pages: 1249-1258

    • DOI

      10.1292/jvms.19-0016

    • NAID

      130007701676

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical usefulness of flash glucose monitoring system in dogs with diabetes mellitus2019

    • Author(s)
      Tamamoto T, Kumano M, Igarashi H, Yonezawa T
    • Journal Title

      J Vet Sci Med Diagn

      Volume: 8(4) Pages: 1-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Excitatory and inhibitory amino acids in cerebrospinal fluid of familial spontaneous epileptic cats.2019

    • Author(s)
      Ogawa F, Hasegawa D, Mizoguchi S, Yonezawa T, Matsuki N.
    • Journal Title

      J Vet Sci Med Diagn.

      Volume: 8(1) Pages: 1-6

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Decreased plasma amino acid concentrations in cats with chronic gastrointestinal diseases and their possible contribution in the inflammatory response.2018

    • Author(s)
      Sakai K, Maeda S, Yonezawa T, Matsuki N.
    • Journal Title

      Veterinary Immunology and Immunopathology

      Volume: 195 Pages: 1-6

    • DOI

      10.1016/j.vetimm.2017.11.001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of tumour-infiltrating regulatory T cells with adverse outcomes in dogs with malignant tumours2018

    • Author(s)
      Sakai K., Maeda S., Yamada Y., Chambers J. K., Uchida K., Nakayama H., Yonezawa T., Matsuki N.
    • Journal Title

      Veterinary and Comparative Oncology

      Volume: 印刷中 Pages: 330-336

    • DOI

      10.1111/vco.12383

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Multiple acquired portosystemic shunts secondary to primary hypoplasia of the portal vein in a cat2018

    • Author(s)
      SUGIMOTO Satoko、MAEDA Shingo、TSUBOI Masaya、SAEKI Kohei、CHAMBERS James K.、YONEZAWA Tomohiro、FUKUSHIMA Kenjiro、FUJIWARA Reina、UCHIDA Kazuyuki、TSUJIMOTO Hajime、MATSUKI Naoaki、OHNO Koichi
    • Journal Title

      J. Vet. Med. Sci.

      Volume: 80 Issue: 6 Pages: 874-877

    • DOI

      10.1292/jvms.17-0648

    • NAID

      130007384664

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] 犬の組織球性肉腫の発生・病態におけるApoptosis Inhibitor of Macrophage (AIM)の 遺伝子変異による影響の検討2020

    • Author(s)
      内田萌菜、米澤智洋、茂木朋貴、藤井渉、盆子原誠、原田慶、小林哲也、前田真吾、桃井康行
    • Organizer
      第16回日本獣医内科学アカデミー
    • Related Report
      2019 Annual Research Report
  • [Presentation] ドコサヘキサエン酸を投与した特発性てんかんの犬の5例2020

    • Author(s)
      米澤智洋、松宮佑樹、三澤嘉久、藤原夏樹、茂木朋貴、前田真吾、桃井康行
    • Organizer
      第16回日本獣医内科学アカデミー
    • Related Report
      2019 Annual Research Report
  • [Presentation] 先天性下垂体性矮小症と診断したトイ・プードルの1例2020

    • Author(s)
      後藤 瞬,今井 巡,松宮 佑樹,米澤 智洋
    • Organizer
      第16回日本獣医内科学アカデミー
    • Related Report
      2019 Annual Research Report
  • [Presentation] Impact of thrombocytosis on lung metastasis and survival in dogs with urothelial carcinoma2019

    • Author(s)
      INOUE A, MOTEGI T, YONEZAWA T , MAEDA S
    • Organizer
      The 2nd Asian Small Animal Specialist Veterinary Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 尿道括約筋不全症の避妊雌犬に対するテストステロン製剤投与の臨床評価2019

    • Author(s)
      西 玲央、茂木 朋貴、前田 真吾、玉原 智史、松木 直章、米澤 智洋
    • Organizer
      日本獣医腎泌尿器学会2019年大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Expression and genetic variation of apoptosis inhibitor of macrophage in canine histiocytic sarcoma2019

    • Author(s)
      Mona UCHIDA, Kazuyuki UCHIDA, Hiroyuki TANI, Makoto BONKOBARA, Shingo MAEDA, Tomohiro YONEZAWA
    • Organizer
      American College of Veterinary Internal Medicine
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] イヌにおけるApoptosis Inhibitor of Macrophage (AIM) の 生体内発現分布2019

    • Author(s)
      内田萌菜, 内田和幸, 前田真吾, 米澤智洋
    • Organizer
      日本獣医臨床病理学会2019年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 5-ALAの内服は慢性腎臓病の猫の尿蛋白/クレアチニン比を減少させる2019

    • Author(s)
      西玲央・内田萌菜・中原理人・前田真吾・林明男・岩谷直・田中徹・米澤智洋
    • Organizer
      第9回ポルフィリン‐ALA学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] γ-グルタミルトランスペプチダーゼ活性検出蛍光プローブを用いた犬の乳腺腫瘍の可視化の試み2019

    • Author(s)
      廣瀬結衣、内田萌菜、坪井誠也、中川貴之、栗木優五、神谷真子、浦野泰照、前田真吾、米澤智洋
    • Organizer
      第162回日本獣医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Mona UCHIDA, Kazuyuki UCHIDA, Hiroyuki TANI, Makoto BONKOBARA, Shingo MAEDA, Tomohiro YONEZAWA2019

    • Author(s)
      Function, expression and genetic variation of apoptosis inhibitor of macrophage (AIM) on canine histiocytic sarcoma
    • Organizer
      The 10th Joint Symposium of Veterinary Research in East Asia
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Feasibility of clinical application of gamma-glutamyl hydroxymethyl rhodamine green for detection of canine breast cancer2018

    • Author(s)
      Y. Hirose, M Uchida, Y. Urano, M. Tsuboi, S. Maeda, T. Yonezawa
    • Organizer
      Proceedings of the 18th biennial congress of the international society for animal clinical pathology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Expression of apoptosis inhibitor of macrophage in canine histiocytic sarcoma and its relation to tumor malignancy2018

    • Author(s)
      M. Uchida, Y. Matsumiya, M. Bonkobara, S. Maeda, T. Yonezawa
    • Organizer
      Proceedings of the 18th biennial congress of the international society for animal clinical pathology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 5-ALAの内服が慢性腎臓病の猫の血中・尿中マーカーに与える影響2018

    • Author(s)
      米澤智洋・内田萌菜・中原理人・前田真吾・林明男・岩谷直・田中徹
    • Organizer
      第8回ポルフィリン‐ALA学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A pilot study on abnormal behaviors in Annexin A5 knockout mice2018

    • Author(s)
      陳文、内田萌菜、米澤智洋、小松浩一郎、中島和久、出野 尚、二藤 彰、汾陽光盛
    • Organizer
      第4回 日本アネキシン研究会年会
    • Related Report
      2018 Annual Research Report

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

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