基本情報
研究分野
1経歴
6-
2015年4月 - 現在
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2011年4月 - 2015年3月
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2005年4月 - 2011年3月
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2000年10月 - 2005年3月
学歴
2-
- 1997年
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- 1993年
委員歴
11-
2020年5月 - 現在
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2014年 - 現在
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2009年 - 現在
受賞
3論文
88-
Legal medicine (Tokyo, Japan) 70 102472-102472 2024年6月15日 査読有りSimilar to that in Europe and the United States, the need for forensic DNA identification in dogs is increasing in Japan. As few studies have used commercial genotyping kits, the effectiveness of the Canine GenotypesTM Panel 2.1 Kit for individual DNA identification in dogs bred in Japan was examined. We genotyped 150 unrelated dogs (50 Golden Retrievers, 50 Miniature Dachshunds, and 50 Shiba Inu) at 18 canine short tandem repeat loci by the Kit. The allele frequency, expected heterozygosity, observed heterozygosity, p-value, power of the discriminant, and of exclusion, polymorphic information content, and random matching probability were calculated for each marker. The random matching probability was subsequently estimated to be 4.394×10-22 in the 150 dogs of the three pure-bred groups based on 18 STR loci; 3.257 × 10-16 in the Golden Retriever, 3.933 × 10-18 in the Miniature Dachshund, and 2.107 × 10-18 in the Shiba Inu breeds. In addition, principal component analysis based on genotype data revealed the Golden Retrievers, Miniature Dachshunds, and Shiba Inus separated into three clusters. The results of the genotype analysis showed that the Canine GenotypesTM Panel 2.1 Kit could be useful for identity testing and tool of population study of canines in Japan.
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Scientific Reports 13(1) 2023年5月25日 査読有りAbstract Histiocytic sarcoma (HS) is an incurable aggressive tumor, and no consensus has been made on the treatment due to its rare occurrence. Since dogs spontaneously develop the disease and several cell lines are available, they have been advocated as translational animal models. In the present study, therefore, we explored gene mutations and aberrant molecular pathways in canine HS by next generation sequencing to identify molecular targets for treatment. Whole exome sequencing and RNA-sequencing revealed gene mutations related to receptor tyrosine kinase pathways and activation of ERK1/2, PI3K-AKT, and STAT3 pathways. Analysis by quantitative PCR and immunohistochemistry revealed that fibroblast growth factor receptor 1 (FGFR1) is over-expressed. Moreover, activation of ERK and Akt signaling were confirmed in all HS cell lines, and FGFR1 inhibitors showed dose-dependent growth inhibitory effects in two of the twelve canine HS cell lines. The findings obtained in the present study indicated that ERK and Akt signaling were activated in canine HS and drugs targeting FGFR1 might be effective in part of the cases. The present study provides translational evidence that leads to establishment of novel therapeutic strategies targeting ERK and Akt signaling in HS patients.
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Veterinary and comparative oncology 2023年2月6日 査読有りCanine prostate cancer (cPCa) is a malignant neoplasm with no effective therapy. The BRAF V595E mutation, corresponding to the human BRAF V600E mutation, is found frequently in cPCa. Activating BRAF mutations are recognized as oncogenic drivers, and blockade of MAPK/ERK phosphorylation may be an effective therapeutic target against BRAF-mutated tumors. The aim of this study was to establish a novel cPCa cell line and to clarify the antitumor effects of MEK inhibitors on cPCa in vitro and in vivo. We established the novel CHP-2 cPCa cell line that was derived from the prostatic tissue of a cPCa patient. Sequencing of the canine BRAF gene in two cPCa cell lines revealed the presence of the BRAF V595E mutation. MEK inhibitors (trametinib, cobimetinib, and mirdametinib) strongly suppressed cell proliferation in vitro, and trametinib showed the highest efficacy against cPCa cells with minimal cytotoxicity to non-cancer COPK cells. Furthermore, we orally administered 0.3 or 1.0 mg/kg trametinib to CHP-2 xenografted mice and examined its antitumor effects in vivo. Trametinib reduced tumor volume, decreased phosphorylated ERK levels, and lowered Ki-67 expression in xenografts in a dose-dependent manner. Although no clear adverse events were observed with administration, trametinib-treated xenografts showed osteogenesis that was independent of dosage. Our results indicate that trametinib induces cell cycle arrest by inhibiting ERK activation, resulting in cPCa tumor regression in a dose-dependent manner. MEK inhibitors, in addition to BRAF inhibitors, may be a targeted agent option for cPCa with the BRAF V595E mutation. This article is protected by copyright. All rights reserved.
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BMC veterinary research 18(1) 384-384 2022年11月3日 査読有り最終著者責任著者BACKGROUND: Multiple myeloma (MM) is an uncommon neoplasm in cats. There is no established standard of treatment due to the rare occurrence of this disease in cats. Bortezomib is a proteasome inhibitor that serves as the first-line drug for MM in humans, but its effectiveness currently is unknown in feline MM. We present here the case report of a feline MM that exhibited a favorable response to bortezomib. CASE PRESENTATION: The case was an 11-year-old non-castrated male domestic cat with light-chain MM presenting with clinical symptoms (anorexia, fatigue, and vomiting), mild azotemia, and pancytopenia. The cat failed on melphalan with prednisolone (MP), so bortezomib (Velcade) was initiated on Day 88. A total of 6 cycles of the treatment was performed, with each treatment cycle consisting of twice-weekly subcutaneous administration for 2 weeks followed by a 1-week rest. The dose of bortezomib was 0.7 mg/m2 for first week and 1.0 mg/m2 for second week in the first cycle. A dose of 0.7 mg/m2 was used for subsequent cycles. Prednisolone was used concomitantly in the first 2 cycles. Following treatment with bortezomib, clinical symptoms disappeared and a decrease in serum globulin and recovery of pancytopenia were noted. A monoclonal gammopathy, overproduction of serum immunoglobulin light chain, and Bence-Jones proteinuria that existed at diagnosis were undetectable on Day 123. A monoclonal gammopathy also was not detectable at the end of the bortezomib treatment (Day 213). Anorexia, fatigue, and marked bone marrow toxicity were experienced when bortezomib was administrated at a dose of 1.0 mg/m2, while no recognizable toxicity was observed at a dose of 0.7 mg/m2 throughout the treatment period. The case was placed on follow-up and there was no evidence of relapse as of Day 243. CONCLUSIONS: Bortezomib was effective and durable for the treatment of this case of feline MM after failure with MP. Bortezomib was well-tolerated in this cat at a dose of 0.7 mg/m2, but not at 1.0 mg/m2. Bortezomib appears to be a drug worthy of further study for the treatment of feline MM.
MISC
15担当経験のある科目(授業)
3-
- 現在獣医臨床腫瘍学 (日本獣医生命科学大学)
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- 現在獣医血液病・免疫病学 (日本獣医生命科学大学)
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- 現在獣医臨床病理学 (日本獣医生命科学大学)
所属学協会
3Works(作品等)
2共同研究・競争的資金等の研究課題
21-
日本学術振興会 科学研究費助成事業 基盤研究(C) 2022年4月 - 2025年3月
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文部科学省: 科学研究費補助金(基盤研究(B)) 2019年 - 2022年
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日本学術振興会 科学研究費助成事業 基盤研究(B) 2018年4月 - 2021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(B) 2015年4月 - 2018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(B) 2014年4月 - 2017年3月
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文部科学省 科学研究費補助金(基盤研究(B)) 2015年 - 2017年
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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) 2013年4月 - 2016年3月
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文部科学省 科学研究費補助金(挑戦的萌芽研究) 2014年 - 2014年
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文部科学省 科学研究費補助金(基盤研究(B)) 2012年 - 2014年
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文部科学省 科学研究費補助金(挑戦的萌芽研究) 2013年 - 2013年
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文部科学省 科学研究費補助金(基盤研究(C)) 2009年 - 2011年
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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) 2007年 - 2008年
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文部科学省 科学研究費補助金(基盤研究(C)) 2006年 - 2007年
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日本学術振興会 科学研究費助成事業 基盤研究(A) 2004年 - 2007年
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日本学術振興会 科学研究費助成事業 基盤研究(B) 2004年 - 2006年
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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) 2004年 - 2005年
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伊藤記念財団助成 2004年 - 2005年
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文部科学省 科学研究費補助金(若手研究(B)) 2004年 - 2005年
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森永奉仕会助成 2003年 - 2004年
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伊藤記念財団助成 2003年 - 2004年
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文部科学省 科学研究費補助金(若手研究(B)) 2002年 - 2004年