研究者データベース

出口 辰弥(デグチ タツヤ)
獣医学研究院 附属動物病院
特任助教

基本情報

所属

  • 獣医学研究院 附属動物病院

職名

  • 特任助教

学位

  • 獣医学博士(北海道大学)

J-Global ID

研究キーワード

  • 免疫療法   獣医学   ミトコンドリア   がん幹細胞   放射線腫瘍学   

研究分野

  • ライフサイエンス / 腫瘍生物学 / 放射線治療

職歴

  • 2019年04月 - 現在 北海道大学 大学院獣医学研究院附属動物病院 特任助教

学歴

  • 2015年04月 - 2019年03月   北海道大学   大学院獣医学研究科   獣医外科学教室
  • 2007年04月 - 2013年03月   麻布大学   獣医学部   獣医学科

所属学協会

  • 日本獣医がん学会   日本獣医師会   日本癌学会   

研究活動情報

論文

  • Tatsuya Deguchi, Kenji Hosoya, Shango Kim, Yusuke Murase, Kumiko Yamamoto, Tomoki Bo, Hironobu Yasui, Osamu Inanami, Mahiro Okumura
    Molecular therapy oncolytics 22 143 - 151 2021年09月24日 
    Metformin has many anti-cancer effects, alone or in combination with radiation. However, the mechanism underlying its radio-sensitized effect is still unclear, especially for cancer stem-like cells (CSCs). Here, the radio-sensitized effect of metformin was investigated, and its mechanism was revealed in CSCs derived from canine osteosarcoma cell line (HMPOS), a canine osteosarcoma cell line. Spheroid cells (SCs) were used as CSCs-rich cells derived from sphere formation, and SCs were compared with normal adherent culture cells (ACs). The radio-sensitizing effect of metformin using clonogenic assay and tumor growth in mice xenograft model were evaluated, and the mechanism of its radio-sensitization focusing on mitochondrial function was revealed. Metformin significantly enhanced radio-sensitivity of SCs through its inhibition of the mitochondrial function, as shown by decreased oxygen consumption, decreased mitochondrial membrane potential, and decreased ATP production. Additionally, SCs had a higher ability of mitochondrial respiration than ACs, which may have caused difference of their sensitivity of metformin and irradiation. In conclusion, mitochondrial function might play an important role in the sensitivity of metformin and irradiation, and drugs that target mitochondrial respiration, such as metformin, are promising radio-sensitizers to target CSCs.
  • Sangho Kim, Kenji Hosoya, Natsuki Fukayama, Tatsuya Deguchi, Masahiro Okumura
    Veterinary medicine and science 7 4 1120 - 1130 2021年07月 
    Allogeneic hematopoietic cell transplantation (HCT) has been an effective treatment for human patients with haematological malignancies (Baron & Storb, 2006; Bair et al., 2020; Copelan et al., 2019). However, the optimal pretransplant conditioning treatment is unclear in canine allogeneic HCT. This pilot study aimed to evaluate the safety and efficacy of total lymphoid irradiation (TLI) with volumetric modulated arc therapy (VMAT) for a nonmyeloablative HCT conditioning. Six healthy dogs were treated with 8 or 12 Gy TLI using VMAT. Haematological and physical changes were recorded over 8 weeks. To assess the effect of peripheral lymphocyte condition, lymphocyte subset and proliferative ability were examined. At the end of the experiment, necropsy was performed. All dogs showed mild-to-moderate neutropenia and thrombocytopenia, and these haematological changes resolved spontaneously. One dog treated with 8 Gy TLI developed transient cutaneous infection. No major complication was seen in the other seven dogs. Myelocytes and erythroblast cytopenia of bone marrow were detected in two dogs treated with 12 Gy TLI. This study is the first report of TLI using VMAT in dogs, and results suggest that this regimen is a feasible nonmyeloablative treatment.
  • Naoya Maekawa, Satoru Konnai, Maki Nishimura, Yumiko Kagawa, Satoshi Takagi, Kenji Hosoya, Hiroshi Ohta, Sangho Kim, Tomohiro Okagawa, Yusuke Izumi, Tatsuya Deguchi, Yukinari Kato, Satoshi Yamamoto, Keiichi Yamamoto, Mikihiro Toda, Chie Nakajima, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
    NPJ precision oncology 5 1 10 - 10 2021年02月12日 
    Immunotherapy targeting programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1) represents promising treatments for human cancers. Our previous studies demonstrated PD-L1 overexpression in some canine cancers, and suggested the therapeutic potential of a canine chimeric anti-PD-L1 monoclonal antibody (c4G12). However, such evidence is scarce, limiting the clinical application in dogs. In the present report, canine PD-L1 expression was assessed in various cancer types, using a new anti-PD-L1 mAb, 6C11-3A11, and the safety and efficacy of c4G12 were explored in 29 dogs with pulmonary metastatic oral malignant melanoma (OMM). PD-L1 expression was detected in most canine malignant cancers including OMM, and survival was significantly longer in the c4G12 treatment group (median 143 days) when compared to a historical control group (n = 15, median 54 days). In dogs with measurable disease (n = 13), one dog (7.7%) experienced a complete response. Treatment-related adverse events of any grade were observed in 15 dogs (51.7%). Here we show that PD-L1 is a promising target for cancer immunotherapy in dogs, and dogs could be a useful large animal model for human cancer research.
  • Deguchi T, Hosoya K, Murase Y, Koangyong S, Kim S, Okumura M
    Veterinary and comparative oncology 2018年12月 [査読有り][通常論文]
  • Takagi S, Kagawa Y, Hanazono K, Murakami S, Deguchi T, Izumi Y, Hosoya K, Kim S, Okumura M
    The Journal of veterinary medical science 80 9 1456 - 1458 2018年09月 [査読有り][通常論文]
  • Takagi S, Takamura D, Deguchi T, Izumi Y, Takeuchi R, Hoshi K, Takeuchi K
    Open veterinary journal 8 4 441 - 444 2018年 [査読有り][通常論文]
  • Naoya Maekawa, Satoru Konnai, Satoshi Takagi, Yumiko Kagawa, Tomohiro Okagawa, Asami Nishimori, Ryoyo Ikebuchi, Yusuke Izumi, Tatsuya Deguchi, Chie Nakajima, Yukinari Kato, Keiichi Yamamoto, Hidetoshi Uemura, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
    SCIENTIFIC REPORTS 7 1 8951  2017年08月 [査読有り][通常論文]
     
    Immunotherapy targeting immune checkpoint molecules, programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), using therapeutic antibodies has been widely used for some human malignancies in the last 5 years. A costimulatory receptor, PD-1, is expressed on T cells and suppresses effector functions when it binds to its ligand, PD-L1. Aberrant PD-L1 expression is reported in various human cancers and is considered an immune escape mechanism. Antibodies blocking the PD-1/PD-L1 axis induce antitumour responses in patients with malignant melanoma and other cancers. In dogs, no such clinical studies have been performed to date because of the lack of therapeutic antibodies that can be used in dogs. In this study, the immunomodulatory effects of c4G12, a canine-chimerised anti-PD-L1 monoclonal antibody, were evaluated in vitro, demonstrating significantly enhanced cytokine production and proliferation of dog peripheral blood mononuclear cells. A pilot clinical study was performed on seven dogs with oral malignant melanoma (OMM) and two with undifferentiated sarcoma. Objective antitumour responses were observed in one dog with OMM (14.3%, 1/7) and one with undifferentiated sarcoma (50.0%, 1/2) when c4G12 was given at 2 or 5 mg/kg, every 2 weeks. c4G12 could be a safe and effective treatment option for canine cancers.
  • A. Matsuyama, S. Takagi, K. Hosoya, Y. Kagawa, K. Nakamura, T. Deguchi, M. Takiguchi
    NEW ZEALAND VETERINARY JOURNAL 65 5 227 - 231 2017年 [査読有り][通常論文]
     
    AIMS: To compare the survival of dogs with completely resected massive hepatocellular carcinoma (HCC) with that of dogs in which HCC were incompletely excised. METHODS: A retrospective cohort study was conducted. Dogs that underwent surgical excision of massive HCC between November 2006 and April 2015 were included. Dogs that died in the perioperative period or were lost to follow-up within 2 months after surgery were excluded. Data were collected from the medical records and a single pathologist examined all available histology slides to confirm the diagnosis of HCC. Surgical margins were defined as complete if no neoplastic cells were seen at the edge of excised tissues, based on original histopathology reports. Progression-free survival (PFS) and overall survival (OS) were compared between dogs with complete surgical margins (CM) and those with incomplete margins (IM) using a log-rank test. RESULTS: Of the 37 dogs included in the study, 25 were allocated to the CM group and 12 to the IM group. Progressive local disease developed after surgery in three dogs in the CM group and seven dogs in the IM group. Three dogs in the CM group and five dogs in the IM group died due to tumour progression. Median PFS was longer for dogs in the CM group (1,000 (95% CI=562-1,438) days) compared to dogs in the IM group (521 (95% CI=243-799) days; p=0.007). OS was also longer for dogs in the CM group (>1,836 days) compared to those in the IM group (median 765 (95% CI=474-1,056) days; p=0.02). CONCLUSIONS AND CLINICAL RELEVANCE: Compared with complete resection, incomplete resection decreased PFS and OS in dogs with massive HCC. Dogs with incompletely excised HCC should be closely monitored for local recurrence, although median OS was >2 years following incomplete excision. Further prospective studies are warranted to confirm these findings.
  • A. Tanabe, T. Deguchi, T. Sato, Y. Nemoto, T. Maruo, H. Madarame, T. Shida, Y. Naya, K. Ogihara, H. Sahara
    VETERINARY AND COMPARATIVE ONCOLOGY 14 3 E93 - E101 2016年09月 [査読有り][通常論文]
     
    Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are a small subpopulation of cancer cells that are responsible for the initiation, recurrence and metastasis of cancer. We previously demonstrated that, using the Hoechst 33342 dye-based side population technique, CSCs/CICs in canine lung adenocarcinoma cell line exist. In this study, as CSCs/CICs are known to form spheres in anchorage-independent environment in vitro, we evaluated the stemness of spheroid cells derived from canine lung adenocarcinoma and osteosarcoma cells by expression of stemness markers, and investigated radioresistance. Spheroid cells showed greater expression of stemness markers Oct-4 and CD133 gene than those of adherent-cultured cells. In nude mouse xenograft models, spheroid cells showed higher tumourigenic ability than adherent-cultured cells. In addition, spheroid cells showed significantly resistant against radioactivity as compared with adherent-cultured cells. These results suggest that spheroid cells could possess stemness and provide a CSCs/CICs research tool to investigate CSCs/CICs of canine tumour cells.
  • Y. Nemoto, T. Maruo, T. Sato, T. Deguchi, T. Ito, H. Sugiyama, T. Ishikawa, H. Madarame, T. Watanabe, T. Shida, H. Sahara
    VETERINARY PATHOLOGY 48 5 1029 - 1034 2011年09月 [査読有り][通常論文]
     
    Accumulating evidence supporting the cancer stem cell (CSC) hypothesis is based on the finding that tumors contain a small population of self-renewing cells that generate differentiated progeny and thereby contribute to tumor heterogeneity. CSCs are reported to exist in several human cancers, yet only a few reports demonstrate the existence of CSCs in primary lung cancer in dogs. In this study, the authors established a cancer cell line derived from a canine primary lung adenocarcinoma and identified a side population (SP) of cells that displayed drug-resistant features. To confirm the characteristics of these SP cells, the authors investigated the tumorigenicity of the cells in vivo by using a nude mouse xenograft model. Only 100 SP cells were able to give rise to new tumors, giving a 10-fold enrichment over the main population (MP) of cells, suggesting that these cells have the cancer-initiating ability of CSCs. Further studies characterizing CSCs in canine lung adenocarcinoma might contribute to the elucidation of the mechanisms of tumorigenesis and to the establishment of novel therapeutic strategies.

講演・口頭発表等

  • 神経膠腫の脊髄への滴下転移に対して全脊髄照射を実施した犬の1例  [通常講演]
    出口辰弥, 細谷謙次, 柄本浩一, 金 尚昊, 奥村正裕
    第21回日本獣医がん学会 2019年07月
  • イヌ骨肉腫細胞株由来Cancer stem-like cellsのミトコンドリアの放射線反応性の解析
    出口辰弥, 細谷謙次, 金 尚昊, 山本久美子, 房 知輝, 安井博宣, 稲波 修, 奥村正裕
    第72回日本酸化ストレス学会 学術集会 2019年06月 口頭発表(一般)
  • メトホルミンのイヌ骨肉腫細胞株由来のCancer stem-like cellsにおける放射線増感効果の解析  [通常講演]
    出口辰弥, 細谷謙次, 金 尚昊, 山本久美子, 房 知輝, 安井博宣, 稲波 修, 奥村正裕
    第21回癌治療増感研究シンポジウム 2019年02月 口頭発表(一般) 奈良
  • Metformin radio-sensitizes cancer stem-like cells but not no-stem cells in canine osteosarcoma cell line by AMPK/mTOR-independent mechanism.  [通常講演]
    Deguchi T, Hosoya K, Murase Y, Kim S, Okumura M
    2018 Veterinary Cancer Society (VCS) Annual Conference 2018年10月 ポスター発表 Louisville, KY, USA
  • Metformin radio-sensitizes cancer stem-like cells derived from canine osteosarcoma cell line.  [通常講演]
    Deguchi T, Hosoya K, Murase Y, Kim S, Okumura M
    The 6th Sapporo Summer Seminar for One Health (SaSSOH) 2018年09月 口頭発表(一般) Sapporo, Hokkaido, Japan
  • メトホルミンのイヌ骨肉腫細胞株由来のCancer stem-like cellsに対する放射線増感効果の解析  [通常講演]
    出口辰弥, 細谷謙次, 村瀬優介, 金 尚昊, 奥村正裕
    第161回日本獣医学会学術集会 2018年09月 口頭発表(一般) つくば
  • Analysis of radioresistance of cancer stem-like cells derived from canine cancer.  [通常講演]
    Deguchi T, Murase Y, Kim S, Hosoya K, Okumura M
    The 5th Sapporo Summer Seminar for One Health (SaSSOH) 2017年09月 口頭発表(一般) Sapporo, Hokkaido, Japan
  • ヌの腫瘍細胞株由来Cancer stem-like cellsの放射線反応性の解析  [通常講演]
    出口辰弥, 細谷謙次, 村瀬優介, 金 尚昊, 奥村正裕
    第160回日本獣医学会学術集会 2017年09月 口頭発表(一般) 鹿児島
  • リン酸トセラニブ投与を実施した再発性鼻腔腫瘍の犬14例の回顧的研究  [通常講演]
    出口辰弥, 細谷謙次, 金 尚昊, 高木 哲, 星野有希, 奥村正裕
    平成28年度北海道地区三学会 2016年09月 口頭発表(一般) 旭川
  • 上唇組織を用いて吻側鼻部の再建を実施した鼻鏡の扁平上皮癌の犬の1例  [通常講演]
    出口辰弥, 細谷謙次, 高木 哲, 金 尚昊, 奥村正裕
    第15回日本獣医がん学会 2016年06月 口頭発表(一般) 東京
  • 再発性悪性末梢神経腫瘍に対して放射線治療を実施した犬の5例  [通常講演]
    出口辰弥, 細谷謙次, 高木 哲, 越後良介, 金 尚昊, 奥村正裕
    第91回獣医麻酔外科学会 2015年12月 口頭発表(一般) 札幌
  • 異所性副腎皮質腺癌により多飲多尿を認めた犬の1例  [通常講演]
    出口辰弥, 細谷謙次, 松本 隆, 賀川由美子, 高木 哲, 星野有希, 金 尚昊, 奥村正裕
    平成27年度北海道地区三学会 2015年09月 口頭発表(一般) 江別
  • 腹腔内播種を伴う卵巣癌に対して全腹部照射(Whole Abdominal Irradiation:WAI)を行った犬の1例  [通常講演]
    出口辰弥, 細谷謙次, 高木 哲, 中村健介, 金 尚昊, 岩木芳美, 奥村正裕
    第12回日本獣医がん学会 2015年07月 口頭発表(一般) 東京
  • 犬における全腹部照射(Whole Abdominal Irradiation:WAI)プロトコールの検討  [通常講演]
    出口辰弥, 細谷謙次, 高木 哲, 星野有希, 中村健介, 金 尚昊, 奥村正裕
    平成26年度北海道地区三学会 2014年09月 口頭発表(一般) 札幌
  • 教育講演
    出口辰弥

その他活動・業績

受賞

  • 2015年12月 日本獣医麻酔外科学会 優秀賞
     再発性悪性末梢神経腫瘍に対して放射線治療を実施した犬の5例 
    受賞者: 出口 辰弥

共同研究・競争的資金等の研究課題

  • イヌ腫瘍に対するミトコンドリア代謝阻害薬の放射線増感効果に関する臨床研究
    日本学術振興会:科学研究費助成事業 若手研究
    研究期間 : 2020年04月 -2022年03月 
    代表者 : 出口 辰弥
  • イヌ腫瘍の免疫抑制機構阻害剤の放射線増感効果における臨床研究
    日本学術振興会:科学研究費助成事業 研究活動スタート支援
    研究期間 : 2019年08月 -2021年03月 
    代表者 : 出口 辰弥
  • 犬の鼻腔腫瘍に対するテーラーメイド放射線治療に向けた癌幹細胞の性質の同定
    北海道大学:リーディングプログラム大学院学生科研費
    研究期間 : 2016年08月 -2017年03月 
    代表者 : 出口 辰弥

教育活動情報

主要な担当授業

  • 伴侶動物獣医療実習Ⅰ
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 伴侶動物、内科、外科、検査、診断、治療
  • 伴侶動物獣医療実習Ⅱ
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 伴侶動物、内科、外科、検査、診断、治療
  • 総合獣医療実習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 臨床病理、画像診断、細胞診、病理解剖、麻酔
  • 夜間・救急獣医療実習Ⅰ
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 獣医学部
    キーワード : 夜間・休日診療、救急処置


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