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Analysis of oncogene addiction and development of molecular-targeted therapy for small animal tumours

Research Project

Project/Area Number 24380173
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Clinical veterinary science
Research InstitutionNippon Veterinary and Life Science University

Principal Investigator

BONKOBARA Makoto  日本獣医生命科学大学, 獣医学部, 准教授 (50343611)

Co-Investigator(Kenkyū-buntansha) TAZAKI Hiroyuki  日本獣医生命科学大学, 獣医学部, 教授 (80231405)
OMI Toshinori  日本獣医生命科学大学, 獣医学部, 教授 (40296091)
TOMIHARI Mizuki  帯広畜産大学, 畜産学部, 講師 (00552754)
Co-Investigator(Renkei-kenkyūsha) SHIMADA Takashi  日本医科大学, 医学部, 教授 (20125074)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2014: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2012: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Keywords犬 / 組織球性肉腫 / oncogene addiction / キナーゼ / ダサチニブ / Oncogene addiction
Outline of Final Research Achievements

To establish foundation of molecular-targeted therapy for small animal tumours, we sought canine tumour-derived cell lines that have “oncogene addiction” and analysed signalling pathway(s) on which they depend. A kinase inhibitor, dasatinib, was found to have potent growth inhibitory activity against some histiocytic sarcoma (HS) lines in vitro and in vivo. We then performed kinome analysis using HS lines and found that 14-3-3 protein gamma is constitutively activated in some HS lines that are sensitive to dasatinib. Because 14-3-3 protein gamma does not have kinase activity, it was considered that dasatinib targeted kinase in upper JNK pathway. From these findings, dasatinib could be a potential therapeutic drug for certain HS cases whose tumour cells have constitutively phosphorylated 14-3-3 protein gamma.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (32 results)

All 2015 2014 2013 2012 Other

All Journal Article (18 results) (of which Peer Reviewed: 16 results,  Acknowledgement Compliant: 2 results,  Open Access: 5 results) Presentation (13 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] Molecular changes associated with the development of resistance to imatinib in an imatinib-sensitive canine neoplastic mast cell line carrying a KIT c.1523A>T mutation2015

    • Author(s)
      Kobayashi M, Kuroki S, Tanaka Y, Moriya Y, Kozutumi Y, Uehara Y, Ono K, Tamura K, Washizu T, Bonkobara M.
    • Journal Title

      Eur J Haematol.

      Volume: In press Issue: 6 Pages: 524-31

    • DOI

      10.1111/ejh.12526

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Dysregulation of tyrosine kinases and use of imatinib in small animal practice2015

    • Author(s)
      Bonkobara M.
    • Journal Title

      Vet J.

      Volume: In press Issue: 2 Pages: 180-188

    • DOI

      10.1016/j.tvjl.2014.12.015

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Molecular Cloning and Gene Expression of Canine Apoptosis Inhibitor of Macrophage2014

    • Author(s)
      Tomura S, Uchida M, Yonezawa T, Kobayashi M, Bonkobara M, Arai S, Miyazaki T, Tamahara S, Matsuki N.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 76 Issue: 12 Pages: 1641-1645

    • DOI

      10.1292/jvms.14-0166

    • NAID

      130004684872

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The genetic association study between polymorphisms in uncoupling protein 2 and uncoupling protein 3 and metabolic data in dogs.2014

    • Author(s)
      Udagawa C, Tada N, Asano J, Ishioka K, Ochiai K, Bonkobara M, Tsuchida S, Omi T.
    • Journal Title

      BMC Res Notes.

      Volume: 7 Issue: 1 Pages: 904-904

    • DOI

      10.1186/1756-0500-7-904

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Decreased Gene Expressions of Insulin Signal Molecules in Canine Hyperadrenocorticism2014

    • Author(s)
      Nozawa S, Oda H, Akiyama R, Ueda K, Saeki K, Shono S, Maruyama N, Murata A, Tazaki H, Mori A, Momota Y, Azakami D, Sako T, Ishioka K.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 76 Issue: 8 Pages: 1177-1182

    • DOI

      10.1292/jvms.14-0033

    • NAID

      130004432193

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Silicon Concentration in Cat Urine and Its Relationship with Other Elements2014

    • Author(s)
      Takahashi F, Mochizuki M, Yogo T, Ishioka K, Yumoto N, Sako T, Ueda F, Tagawa M, Tazaki H
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 76 Issue: 4 Pages: 569-572

    • DOI

      10.1292/jvms.13-0356

    • NAID

      130003382405

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low blood cell counts in wild Japanese monkeys after the Fukushima Daiichi nuclear disaster.2014

    • Author(s)
      Ochiai K, Hayama S, Nakiri S, Nakanishi S, Ishii N, Uno T, Kato T, Konno F, Kawamoto Y, Tsuchida S, Omi T.
    • Journal Title

      Sci Rep.

      Volume: 4 Issue: 1 Pages: 5793-5793

    • DOI

      10.1038/srep05793

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The proteasome inhibitor bortezomib inhibits the growth of canine malignant melanoma cells in vitro and in vivo.2013

    • Author(s)
      Ito K, Kobayashi M, Kuroki S, Sasaki Y, Iwata T, Mori K, Kuroki T, Ozawa Y, Tetsuka M, Nakagawa T, Hiroi T, Yamamoto H, Ono K, Washizu T, Bonkobara M.
    • Journal Title

      Vet J.

      Volume: 3 Issue: 3 Pages: 577-582

    • DOI

      10.1016/j.tvjl.2013.08.003

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Analysis of mitochondrial DNA HVR1 haplotype of pure-bred domestic dogs in Japan.2013

    • Author(s)
      Sugiyama S, Chong YH, Shito M, Kasuga M, Kawakami T, Udagawa C, Aoki H, Bonkobara M, Tsuchida S, Sakamoto A, Okuda H, Nagai A, Omi T.
    • Journal Title

      Leg Med (Tokyo).

      Volume: 15 Issue: 6 Pages: 303-309

    • DOI

      10.1016/j.legalmed.2013.08.005

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Imatinib-associated tumour response in a dog with a non-resectable gastrointestinal stromal tumour harbouring a c-kit exon 11 deletion mutation.2013

    • Author(s)
      Kobayashi M, Kuroki S, Ito K, Yasuda A, Sawada H, Ono K, Washizu T, Bonkobara M.
    • Journal Title

      Vet J.

      Volume: 198 Issue: 1 Pages: 271-274

    • DOI

      10.1016/j.tvjl.2013.05.035

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular cloning and tumour suppressor function analysis of canine REIC/Dkk-3 in mammary gland tumours2013

    • Author(s)
      Ochiai, K., Watanabe, M., Azakami, D., Michishita, M., Yoshikawa, Y., Udagawa, C., Metheenukul, P., Chahomchuen, T., Aoki, H., Kumon, H., Morimatsu, M., Omi, T.
    • Journal Title

      Vet. J

      Volume: 197(3) Issue: 3 Pages: 769-775

    • DOI

      10.1016/j.tvjl.2013.04.024

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Semiquantitative multi-analysis of plasma obtained from Romney lambs (Ovis aries) by inductively coupled plasma mass spectrometry, and the classification according to feed type2013

    • Author(s)
      Takahashi F, Mochizuki M, Sato T, Katayama K, Kenyon PR, Morris ST, Kemp PD, Ozawa, T, Ueda F, Tazaki H
    • Journal Title

      Animal Science Journal

      Volume: in press Issue: 6 Pages: 496-501

    • DOI

      10.1111/asj.12027

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of dasatinib as an in vitro potent growth inhibitor of canine histiocytic sarcoma cells2013

    • Author(s)
      Ito K, Kuroki S, Kobayashi M, Ono K, Washizu T, Bonkobara M
    • Journal Title

      Veterinary Journal

      Volume: (In press) Issue: 3 Pages: 536-540

    • DOI

      10.1016/j.tvjl.2012.12.016

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Validation of the prognostic value of histopathological grading or c-kit mutation in canine cutaneous mast cell tumours: a retrospective cohort study2013

    • Author(s)
      Takeuchi Y, Fujino Y, Watanabe M, Takahashi M, Nakagawa T, Takeuchi A, Bonkobara M, Kobayashi T, Ohno K, Uchida K, Asano K, Nishimura R, Nakayama H, Sugano S, Ohashi Y, Tsujimoto H
    • Journal Title

      Vet J

      Volume: 196 Issue: 3 Pages: 492-498

    • DOI

      10.1016/j.tvjl.2012.11.018

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The DC-HIL ligand syndecan-4 is a negative regulator of T-cell allo-reactivity responsible for graft-versus-host disease.2013

    • Author(s)
      Chung JS, Tomihari M, Tamura K, Kojima T, Cruz PD Jr, Ariizumi K
    • Journal Title

      Immunology.

      Volume: 138(2) Issue: 2 Pages: 173-182

    • DOI

      10.1111/imm.12027

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Non-targeted analyses of animal plasma : betaine and choline represent the nutritional and metabolic status2012

    • Author(s)
      Katayama K, Sato T, Arai T, Amao H, Ohta Y, Ozawa T, Kenyon PR, Tazaki H
    • Journal Title

      Journal of Animal Physiology and Animal Nutrition

      Volume: 97 Issue: 1 Pages: 119-125

    • DOI

      10.1111/j.1439-0396.2011.01250.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Investigation of cadmium contamination using hair of the Japanese macaque (Macaca fuscata) from Shimokita Peninsula, Aomori Prefecture in Japan.2012

    • Author(s)
      Mariko MOCHIZUKI
    • Journal Title

      Bulltein of Environemtal Contamination and Toxicology

      Volume: 89 Issue: 3 Pages: 577-579

    • DOI

      10.1007/s00128-012-0694-8

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of a PCR analysis method for canine BRCA22012

    • Author(s)
      Yoshikawa Y, Morimatsu M, Ochiai K, Okuda K, Taoda T, Chikazawa S, Shimamura A, Omi T, Bonkobara M, Orino K, Watanabe K.
    • Journal Title

      BMC Res Notes

      Volume: (in press) Issue: 1 Pages: 173-173

    • DOI

      10.1186/1756-0500-5-173

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 獣医療における分子標的薬の将来展望2015

    • Author(s)
      盆子原誠
    • Organizer
      獣医内科アカデミー
    • Place of Presentation
      横浜
    • Year and Date
      2015-02-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] イマチニブの登場と肥満細胞腫の治療2014

    • Author(s)
      盆子原誠
    • Organizer
      獣医内科アカデミー
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] イマチニブが奏効した犬の消化管間質腫瘍の1症例2013

    • Author(s)
      小林正人、黒木詩織、伊藤慶太、安田暁子、澤田治、美小野憲一郎、鷲巣月美、盆子原誠
    • Organizer
      獣医臨床病理学会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Molecular basis of imatinib therapy in mast cell tumors2013

    • Author(s)
      Makoto BONKOBARA
    • Organizer
      WSAVA FASAVA 2013
    • Place of Presentation
      ニュージーランド
    • Related Report
      2012 Annual Research Report
  • [Presentation] Molecular-targeting therapy with imatinib in mast cell tumors2013

    • Author(s)
      Makoto BONKOBARA
    • Organizer
      WSAVA FASAVA 2013
    • Place of Presentation
      ニュージーランド
    • Related Report
      2012 Annual Research Report
  • [Presentation] In vitro Screening of Compounds led to the Identification of Dasatinib as a Potent Growth Inhibitor for Canine Histiocytic Sarcoma Cells2013

    • Author(s)
      Keita ITO, Shiori KUROKI, Masato KOBAYASHI, Jason Wilson, Tsukimi WASHIZU, Makoto BONKOBARA
    • Organizer
      WSAVA FASAVA 2013
    • Place of Presentation
      ニュージーランド
    • Related Report
      2012 Annual Research Report
  • [Presentation] Molecular targeted therapy with imatinib in canine and feline mast cell tumor2012

    • Author(s)
      Makoto BONKOBARA
    • Organizer
      2012 RIVM International Symposium
    • Place of Presentation
      韓国
    • Related Report
      2012 Annual Research Report
  • [Presentation] Development of Y-chromosomal microsatellite markers in Japanese macaque (Macaca fuscata) population of Fukushima2012

    • Author(s)
      Toshinori OMI, Masayuki SHITOH, Chihiro UDAGAWA, Naomi DADA, Yong Hwa CHONG, Kazuhiko OCHIAI, Atushi SAKAMOTO, Shuichi TSUCHIDA, Shinichi HAYAMA
    • Organizer
      33th International Conference on Animal Genetics
    • Place of Presentation
      オーストラリア
    • Related Report
      2012 Annual Research Report
  • [Presentation] 犬組織球性肉腫に対するダサチニブの増殖抑制効果に関する研究2012

    • Author(s)
      伊藤慶太、池谷早代、竹下恭平、黒木詩織、小林正人、盆子原誠、鷲巣月美
    • Organizer
      第154回日本獣医学会学術集会
    • Place of Presentation
      岩手
    • Related Report
      2012 Annual Research Report
  • [Presentation] 犬の悪性黒色腫細胞に対するBortezomibの増殖抑制効果に関する研究2012

    • Author(s)
      手塚雅典、中川朋子、廣井輝代、山本仁美、小澤佑太、伊藤慶太、黒木詩織、小林正人、盆子原誠、鷲巣月美
    • Organizer
      第154回日本獣医学会学術集会
    • Place of Presentation
      岩手
    • Related Report
      2012 Annual Research Report
  • [Presentation] 犬のイマチニブ耐性肥満細胞腫細胞株の樹立と耐性化機構の解析2012

    • Author(s)
      田中優、小堤友香梨、守谷友加里、上原裕司、小林正人、杉崎修、伊藤慶太、黒木詩織、盆子原誠、鷲巣月美
    • Organizer
      第154回日本獣医学会学術集会
    • Place of Presentation
      岩手
    • Related Report
      2012 Annual Research Report
  • [Presentation] イヌ乳腺腫瘍関連遺伝子BRCA2のBRC repeat 3に存在するSNPsの頻度および機能に及ぼす影響の検討2012

    • Author(s)
      落合和彦、塩入弓絵、染田沙織、大澤有加、宇田川智野、森松正美、吉川泰永、盆子原誠、土田修一、近江俊徳
    • Organizer
      第155回日本獣医学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] イヌUCP2およびUCP3 : SNPディスカバリーと2犬種のSNPジェノタイピング2012

    • Author(s)
      宇田川智野、多田尚美、青木博史、盆子原誠、土田修一、落合和彦、石岡克己、鄭英和、近江俊徳
    • Organizer
      第155回日本獣医学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Remarks] 日本獣医生命科学大学 科学研究費補助金

    • URL

      http://www.nvlu.ac.jp/research/005.html/

    • Related Report
      2014 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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