Analysis of the epigenetic changes in canine lymphoma cells

• Project/Area Number: 24580460
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Clinical veterinary science
• Research Institution: Yamaguchi University
• Principal Investigator: OKUDA Masaru 山口大学, 獣医学部, 教授 (10325243)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: リンパ腫 / 犬 / エピジェネティック / メチル化 / アセチル化 / 抗癌剤 / 造血器腫瘍 / HAT / HDAC

Outline of Final Research Achievements

To improve the treatment of the canine lymphoma patients, we focused on the epigenetic changes of the canine lymphoma cells. Our first study suggests that the detection of H3K18Ac/27Ac by the western blotting may be an appropriate method for the detection of the acetylation status in canine lymphoma cells, and if it presents, the mRNA and protein analysis of CREBBP/EP300 should be explored.
In the second study, we showed that MGMT was strongly correlated with the resistance of canine lymphoma cell lines to an anti-cancer agent, lomustine. Moreover, we show that there were two types of lymphoma cells; ones that possess the MGMT activity and show low sensitivity to lomustine, and others that do not possess the MGMT activity and show high sensitivity to lomustine. However, the canine lymphoma cell lines did not show significant correlation between the methylation status and the MGMT suppression levels.

Research Products

• [Journal Article] O6-Methylguanine-DNA methyltransferase expression causes lomustine resistance in canine lymphoma cells (2015)
  • Author(s): S. Kambayashi, K. Minami, Y. Ogawa, T. Hamaji, C. C. Hwang, M. Igase, H. Hiraoka, T. Shimokawa Miyama, S. Noguchi, K. Baba, T. Mizuno and M. Okuda
  • Journal Title: Canadian Journal of Veterinary Research Volume: 79
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Oncolytic reovirus in canine mast cell tumor. (2013)
  • Author(s): Hwang CC, Umeki S, Kubo M, Hayashi T, Shimoda H, Mochizuki M, Maeda K, Baba K, Hiraoka H, Coffey M, Okuda M, Mizuno T
  • Journal Title: Plos One Volume: 8 Issue: 9 Pages: e73555-e73555
  • DOI: 10.1371/journal.pone.0073555
  • Peer Reviewed
• [Journal Article] Establishment of Five Canine Lymphoma Cell Lines and Tumor Formation in a Xenotransplantation Model (2013)
  • Author(s): Umeki, S., Ema, Y., Suzuki, R., Kubo, M., Hayashi, T., Okamura, Y., Yamazaki, J., Tsujimoto, H., Tani, K., Hiraoka, H., Okuda, M. and Mizuno, T
  • Journal Title: Journal of Veterinary Medical Science Volume: 75 Issue: 4 Pages: 467-474
  • DOI: 10.1292/jvms.12-0448
  • NAID: 130002502194
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed
• [Journal Article] Development of high-grade B-cell lymphoma concurrent with T-cell chronic lymphocytic leukemia in a dog. (2012)
  • Author(s): Okawa T, Hiraoka H, Wada Y, Baba K, Itamoto K, Mizuno T, Okuda M.
  • Journal Title: J Vet Med Sci Volume: 5 Pages: 677-680
  • NAID: 130001879878
  • Peer Reviewed
• [Presentation] Role of Hypoxia Iducible Factor (HIF)-1a in canine lymphoma. (2013)
  • Author(s): Kambayashi S, Hamaji T, Igase M, Mizuno T, Okuda M
  • Organizer: The 3rd Asian Meeting of Animal Medicine Specialties
  • Place of Presentation: Bogor, Indonesia
• [Presentation] 犬リンパ腫における低酸素誘導因子1a（HIF-1a）の解析 (2013)
  • Author(s): 上林聡之，浜地雄大，伊賀瀬雅也，馬場健司，水野拓也，奥田優
  • Organizer: 第156回日本獣医学会学術集会
  • Place of Presentation: 岐阜大学（岐阜市）