基本情報
- 所属
- 日本獣医生命科学大学 獣医学部 獣医保健看護学科 応用部門 病態病理学研究分野 准教授
- 学位
- 博士(獣医学)(北海道大学)
- J-GLOBAL ID
- 200901028845574383
- researchmap会員ID
- 0000014920
研究キーワード
3委員歴
3-
2020年4月 - 現在
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2019年10月 - 現在
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2015年12月 - 現在
受賞
2-
1997年1月
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1995年1月
主要な論文
85-
Journal of Comparative Pathology 201 23-27 2023年2月 査読有り
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Oncology reports 47(4) 2022年4月 査読有りHemangiosarcoma (HSA) is a malignant neoplasm that occurs in humans and canines with a poor prognosis owing to metastatic spread, despite effective treatment. The frequency of spontaneous HSA development is higher in canines than in humans. Therefore, canine HSA is a useful model of intractable human disease, which requires early detection and an effective therapeutic strategy. A high frequency of the p110α phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit alpha (PIK3CA) mutations is detected in a comprehensive genome‑wide analysis of canine cases of HSA. The present cloned the full‑length cDNA of canine PIK3CA and identified a mutation in codon 1047 from canine cases of HSA and cell lines that were established from these. The enforced expression of the 1047th histidine residue (H1047)R or L mutants of canine PIK3CA in HeLa cells enhanced epidermal growth factor receptor (EGFR) signaling via Akt phosphorylation. PIK3CA mutant canine HSA cell lines exhibited the hyperphosphorylation of Akt upon EGF stimulation as well. Alpelisib, a molecular targeted drug against PIK3CA activating mutations, exerted a significant antitumor effect in canine PIK3CA‑mutated HSA cell lines. By contrast, it had no significant effect on canine mammary gland tumor cell lines harboring PIK3CA mutations. On the whole, the findings of the present study suggest that alpelisib may be highly effective against PIK3CA mutations that occur frequently in canine HSA.
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Cancer science 109(5) 1480-1492 2018年5月 査読有り筆頭著者Previously no mouse gastric cancer cell lines have been available for transplantation into C57BL/6 mice. However, a gastric cancer model in immunocompetent mice would be useful for analyzing putative therapies. N-Methyl-N-nitrosourea (MNU) was given in drinking water to C57BL/6 mice and p53 heterozygous knockout mice. Only 1 tumor from a p53 knockout mouse could be cultured and the cells s.c. transplanted into a C57BL/6 mouse. We cultured this s.c. tumor, and subcloned it. mRNA expression in the most aggressive YTN16 subline was compared to the less aggressive YTN2 subline by microarray analysis, and fibroblast growth factor receptor 4 (FGFR4) in YTN16 cells was knocked out with a CRISPR/Cas9 system and inhibited by an FGFR4 selective inhibitor, BLU9931. These transplanted cell lines formed s.c. tumors in C57BL/6 mice. Four cell lines (YTN2, YTN3, YTN5, YTN16) were subcloned and established. Their in vitro growth rates were similar. However, s.c. tumor establishment rates, metastatic rates, and peritoneal dissemination rates of YTN2 and YTN3 were lower than for YTN5 and YTN16. YTN16 established 8/8 s.c. tumors, 7/8 with lung metastases, 3/8 with lymph node metastases and 5/5 with peritoneal dissemination. FGFR4 expression by YTN16 was 121-fold higher than YTN2. FGFR4-deleted YTN16 cells failed to form s.c. tumors and showed lower rates of peritoneal dissemination. BLU9931 significantly inhibited the growth of peritoneal dissemination of YTN16. These studies present the first transplantable mouse gastric cancer lines. Our results further indicate that FGFR4 is an important growth signal receptor in gastric cancer cells with high FGFR4 expression.
MISC
46書籍等出版物
2講演・口頭発表等
146-
第14回アジア保全医学会/第27回日本野生動物医学会 2021合同大会 2021年9月21日 北海道大学
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第14回アジア保全医学会/第27回日本野生動物医学会 2021合同大会 2021年9月21日 北海道大学
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第14回アジア保全医学会/第27回日本野生動物医学会 2021合同大会 2021年9月21日 北海道大学
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第14回アジア保全医学会/第27回日本野生動物医学会 2021合同大会 2021年9月21日 北海道大学
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日本毒性病理学会講演要旨集 2010年2月
所属学協会
6共同研究・競争的資金等の研究課題
5-
2024年4月 - 2025年3月
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2021年4月 - 2022年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2019年4月 - 2022年3月
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日本学術振興会 科学研究費助成事業 若手研究(B) 2014年4月 - 2017年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2011年4月 - 2017年3月
学術貢献活動
1-
企画立案・運営等日本獣医生命科学大学 獣医保健看護学科 病態病理学研究分野 × 付属博物館 共催