Companion diagnostics and risk management on mast cell tumors in dogs

• Project/Area Number: 15H02478
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: Tanaka Akane 東京農工大学, (連合)農学研究科(研究院), 教授 (80418673)
• Co-Investigator(Kenkyū-buntansha): 古市 達哉 岩手大学, 農学部, 教授 (30392103) ; 永岡 謙太郎 東京農工大学, (連合)農学研究科(研究院), 教授 (60376564) ; 種田 久美子 東京農工大学, (連合)農学研究科(研究院), 研究員 (40750469)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥42,510,000 (Direct Cost: ¥32,700,000、Indirect Cost: ¥9,810,000); Fiscal Year 2018: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000); Fiscal Year 2017: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000); Fiscal Year 2016: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000); Fiscal Year 2015: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
• Keywords: 肥満細胞腫 / 病態 / 診断 / 検査 / 遺伝子 / 肥満細胞 / 増殖 / 分化 / 小胞体ストレス / 低酸素応答 / 診断・検査

Outline of Final Research Achievements

Using in vitro experiments, we showed that protein expression levels of GR were closely related to glucocorticoid sensitivity of the host dog.By the analysis of GR protein expression levels in clinical samples, we found the significant correlation between GR protein levels and glucocorticoid sensitivity of the host. Thus, detecting GR protein levels may predict glucocorticoid sensitivity in the treatment of dogs with mast cell tumors. We also established the flow cytometric method for detecting circulating mast cell tumor cells for early diagnosis for recurrence of mast cell tumors in dogs.

Academic Significance and Societal Importance of the Research Achievements

臨床獣医学、中でも小動物臨床への社会的要請は高い。小動物臨床の現場における、伴侶動物の死因のトップは悪性腫瘍であり、発見や診断が遅れた場合の予後は悪い。肥満細胞腫は、ヒトには少ないが、小動物、とりわけイヌに好発し、初期治療が遅れると極めて悪性の転機をたどることから、厄介な腫瘍と考えられてきた。しかしながら代表者らが中心となって実施してきた分子生物学的手法を用いた解析研究から、イヌ肥満細胞腫に対する理解が深まり、様々な治療プロトコル、とりわけ分子標的治療という選択肢が付加されたことは、この腫瘍の攻略に大きく貢献した。さらに肥満細胞が関与するアレルギーの制御についても知見を提供した。

Research Products

• [Int'l Joint Research] University of Manchester(英国)
• [Int'l Joint Research] Medical University of Vienna(Austria)
• [Int'l Joint Research] ウイーン獣医科大学/ウイーン医科大学(オーストリア)
• [Int'l Joint Research] ウイーン医科大学(オーストリア)
• [Journal Article] Gene Expression Profile of Olfactory Transduction Signaling in an Animal Model of Human Multiple Sclerosis (2019)
  • Author(s): Kim Jeongtae、Ahn Meejung、Choi Yuna、Ekanayake Poornima、Park Chul Min、Moon Changjong、Jung Kyungsook、Tanaka Akane、Matsuda Hiroshi、Shin Taekyun
  • Journal Title: Experimental Neurobiology Volume: 28 Issue: 1 Pages: 74-84
  • DOI: 10.5607/en.2019.28.1.74
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cloning and Detection of Equine Histidine-Rich Glycoprotein (2019)
  • Author(s): Muko Ryo、Amagai Yosuke、Matsuda Kenshiro、Matsuda Hiroshi、Tanaka Akane
  • Journal Title: Journal of Equine Veterinary Science Volume: 73 Pages: 121-126
  • DOI: 10.1016/j.jevs.2018.12.009
  • Peer Reviewed / Open Access
• [Journal Article] Oral Administration of Meloxicam Suppresses Low-Dose Endotoxin Challenge?Induced Pain in Thoroughbred Horses (2019)
  • Author(s): Urayama Shuntaro、Tanaka Akane、Kusano Kanichi、Sato Hiroaki、Nagashima Tsuyoshi、Fukuda Ippei、Fujisawa Chihiro、Matsuda Hiroshi
  • Journal Title: Journal of Equine Veterinary Science Volume: 77 Pages: 139-143
  • DOI: 10.1016/j.jevs.2019.03.001
  • Peer Reviewed / Open Access
• [Journal Article] Reduction in the colonization of Staphylococcus aureus on the skin surface under calcium-/magnesium-depleted conditions. Letters in Applied Microbiology. (2018)
  • Author(s): Amagai Y, Makita Y, Takai M, Muko R, Matsuda H, Tanaka A.
  • Journal Title: Letters in Applied Microbiology Volume: - Issue: 4 Pages: 343-347
  • DOI: 10.1111/lam.13037
  • Peer Reviewed / Open Access
• [Journal Article] Molecular allergen profiling in horses by microarray reveals Fag e 2 from buckwheat as a frequent sensitizer (2018)
  • Author(s): Einhorn L.、Hofstetter G.、Brandt S.、Hainisch E. K.、Fukuda I.、Kusano K.、Scheynius A.、Mittermann I.、Resch-Marat Y.、Vrtala S.、Valenta R.、Marti E.、Rhyner C.、Crameri R.、Satoh R.、Teshima R.、Tanaka A.、Sato H.、Matsuda H.、Pali-Scholl I.、Jensen-Jarolim E.
  • Journal Title: Allergy Volume: 73 Issue: 7 Pages: 1436-1446
  • DOI: 10.1111/all.13417
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mast cell hyperactivity underpins the development of oxygen-induced retinopathy. (2017)
  • Author(s): Matsuda K, Okamoto N, Kondo M, Arkwright PD, Karasawa K, Ishizaka S, Yokota S, Matsuda A, Jung K, Oida K, Amagai Y, Jang H, Noda E, Kakinuma R, Yasui K, Kaku U, Mori Y, Onai N, Ohteki T, Tanaka A, Matsuda H
  • Journal Title: J. Clin. Invest. Volume: 127 Issue: 11 Pages: 3987-4000
  • DOI: 10.1172/jci89893
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effective induction of death in mesothelioma cells with magnetite nanoparticles under an alternating magnetic field (2017)
  • Author(s): Matsuda Shofu、Nakajima Eri、Nakanishi Takuya、Hitsuji Airi、Zhang Hong、Tanaka Akane、Matsuda Hiroshi、Momma Toshiyuki、Osaka Tetsuya
  • Journal Title: Materials Science and Engineering: C Volume: 81 Pages: 90-96
  • DOI: 10.1016/j.msec.2017.07.023
  • Peer Reviewed / Open Access
• [Journal Article] Amelioration of atopic-like skin conditions in NC/Tnd mice by topical application with distilled Alpinia intermedia Gagnep extracts (2017)
  • Author(s): Amagai Yosuke、Katsuta Chihiro、Nomura Yoshihiro、Oida Kumiko、Matsuda Kenshiro、Jang Hyosun、Ahn Ginnae、Hamasaki Tetsuyoshi、Matsuda Hiroshi、Tanaka Akane
  • Journal Title: The Journal of Dermatology Volume: 44 Issue: 11 Pages: 1238-1247
  • DOI: 10.1111/1346-8138.13995
  • NAID: 40022167303
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Development of new therapy for canine mammary cancer with recombinant measles virus (2016)
  • Author(s): Shoji Koichiro、Yoneda Misako、Fujiyuki Tomoko、Amagai Yosuke、Tanaka Akane、Matsuda Akira、Ogihara Kikumi、Naya Yuko、Ikeda Fusako、Matsuda Hiroshi、Sato Hiroki、Kai Chieko
  • Journal Title: Molecular Therapy Oncolytics Volume: 3 Pages: 15022-15022
  • DOI: 10.1038/mto.2015.22
  • Peer Reviewed / Open Access
• [Journal Article] Swing time ratio, a new parameter of gait disturbance, for the evaluation of the severity of neuropathic pain in a rat model of partial sciatic nerve ligation. (2016)
  • Author(s): Matsuda K, Orito K, Amagai Y, Jang H, Matsuda H, Tanaka A.
  • Journal Title: J Pharmacol Toxicol Methods. Volume: 79 Pages: 7-14
  • DOI: 10.1016/j.vascn.2015.12.004
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Linoleic acid salt with ultrapure soft water as an antibacterial combination against dermato-pathogenic Staphylococcus spp. (2016)
  • Author(s): Jang H, Makita Y, Jung K, Ishizaka S, Karasawa K, Oida K, Takai M, Matsuda H, Tanaka A.
  • Journal Title: J Appl Microbiol. Volume: 120 Issue: 2 Pages: 280-288
  • DOI: 10.1111/jam.13012
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Crosstalk of carcinoembryonic antigen and transforming growth factor-β via their receptors: comparing human and canine cancer. (2015)
  • Author(s): Jensen-Jarolim E, Fazekas J, Singer J, Hofstetter G, Oida K, Matsuda H, Tanaka A.
  • Journal Title: Cancer Immunology and Immunotherapy Volume: 64 Issue: 5 Pages: 531-537
  • DOI: 10.1007/s00262-015-1684-6
  • Peer Reviewed / Open Access
• [Journal Article] A point mutation in the extracellular domain of KIT promotes tumorigenesis of mast cells via ligand-independent auto-dimerization (2015)
  • Author(s): Amagai Y, Matsuda A, Jung K, Oida K, Jang H, Ishizaka S, Matsuda H, Tanaka A
  • Journal Title: Scientific Reports Volume: 12 Issue: 1 Pages: 9775-9775
  • DOI: 10.1038/srep09775
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ウマ histidine-rich glycoprotein のクローニング及び検出 (2018)
  • Author(s): 向 亮、松田浩珍、田中あかね
  • Organizer: 第３１回日本ウマ科学会学術集会
• [Presentation] 未熟網膜症病態発現機構の分子解析：マスト細胞の必要性 (2018)
  • Author(s): 松田研史郎、田中あかね、松田浩珍
  • Organizer: 第１６１回日本獣医学会学術集会
• [Presentation] 生体内におけるマスト細胞の低酸素応答機構の解析 (2018)
  • Author(s): 雨貝陽介、松田浩珍、田中あかね
  • Organizer: 第１６１回日本獣医学会学術集会
• [Presentation] 伴侶動物のアレルギーと病態モデルとしての有用性 (2017)
  • Author(s): 田中あかね
  • Organizer: 日本アレルギー学会学術集会
  • Invited
• [Presentation] 皮膚バリアとアレルギー疾患との関係 (2017)
  • Author(s): 田中あかね
  • Organizer: 第６回TOBIRA研究交流フォーラム
  • Invited
• [Presentation] Amelioration of atopic-itch sensation in NC/Tnd mice by beta-pinene, the major component contained in distilled Alpinia intermedia Gagnep extracts. (2017)
  • Author(s): Amagai Y, Matsuda H, Tanaka A
  • Organizer: 9th World Congress on Itch
  • Int'l Joint Research
• [Presentation] NC/Tndマウスにおける皮膚炎誘導によるフィラグリン過発現の検討 (2017)
  • Author(s): 籾山綾子、松田浩珍、田中あかね
  • Organizer: 第２７回国際かゆみシンポジウム
  • Int'l Joint Research
• [Presentation] Pathological proliferation of mast cells resulting from either an extracellular domain mutation or stem cell factor autocrine/paracrine. (2016)
  • Author(s): Amagai Y, Matsuda H, Tanaka A.
  • Organizer: 欧州アレルギー臨床免疫学会2016
  • Place of Presentation: オーストリア・ウイーン
  • Year and Date: 2016-06-12
  • Int'l Joint Research
• [Presentation] 細胞外ドメインの点変異によるKIT活性化機構の解析 (2015)
  • Author(s): 雨貝陽介、松田浩珍、田中あかね
  • Organizer: 第１５８回日本獣医学会学術集会
  • Place of Presentation: 北里大学（青森県・十和田市）
  • Year and Date: 2015-09-08
• [Presentation] Distinct activation of dimerized KIT receptors resulting from a point mutation in the extracellular domain and KIT inhibitor actions (2015)
  • Author(s): 雨貝陽介、松田浩珍、田中あかね
  • Organizer: Conference for BioSignal and Medicine 2015
  • Place of Presentation: エクシブ那須白川（福島県・西白河）
  • Year and Date: 2015-07-01
  • Int'l Joint Research
• [Book] Mast Cell Tumors (Chapter 4 in Canine Medicine) (2016)
  • Author(s): Amagai Y and Tanaka A
  • Total Pages: 16
  • Publisher: INTECH
• [Remarks] 研究室ホームページ
  • URL: http://web.tuat.ac.jp/~mol_path/
• [Remarks] 研究室URL
  • URL: http://web.tuat.ac.jp/~mol_path/
• [Remarks] 研究室のHP
  • URL: http://web.tuat.ac.jp/~mol_path/