Updated on 2025/07/04

写真a

 
TAZAWA Hiroshi
 
Organization
Scheduled update Associate Professor
Position
Associate Professor
External link

Degree

  • 医学博士 ( 秋田大学 )

Research Interests

  • Gastroenterological Surgery

  • Gene therapy

Research Areas

  • Life Science / Digestive surgery

  • Life Science / Tumor diagnostics and therapeutics

Education

  • Akita University   大学院   医学研究科

    1996.4 - 2000.3

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  • Akita University   医学部   医学科

    1989.4 - 1995.3

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  • 富山県立高岡高等学校     普通科

    1986.4 - 1989.3

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Research History

  • Okayama University   新医療研究開発センター 探索的医薬品開発室   Associate Professor

    2016.7

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  • Okayama University   新医療研究開発センター 探索的医薬品開発室   Assistant Professor

    2011.10 - 2016.6

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  • Okayama University   遺伝子・細胞治療センター   Assistant Professor

    2010.4 - 2011.9

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  • Okayama University   Graduate School of Medicine , Dentistry and Pharmaceutical Sciences

    2007.12 - 2010.3

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  • 国立がんセンター研究所   研究員

    2005.2 - 2007.11

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Professional Memberships

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Committee Memberships

  • 日本バイオセラピィ学会   評議員  

    2022.6   

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  • 日本癌学会   評議員  

    2019.1   

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    Committee type:Academic society

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  • 日本遺伝子細胞治療学会   評議員  

    2017.7   

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    Committee type:Academic society

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Papers

  • Grafting Islets to a Prevascularized Subcutaneous Site to Improve Transplant Survival and Function: A Mouse Model. Reviewed International journal

    Tsuyoshi Okada, Takashi Kuise, Kenjiro Kumano, Hiroshi Tazawa, Toshiyoshi Fujiwara

    Transplantation proceedings   2025.6

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    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: The subcutaneous space is regarded as a potential site for islet transplantation; however, hypoxic conditions are a major drawback. We hypothesized that islet transplantation into a prevascularized subcutaneous space created using in-body tissue architecture technology would improve islet engraftment and contribute to maintaining the function of transplanted islets. METHODS: Five hundred syngeneic islets were transplanted into the prevascularized subcutaneous space (PSS) constructed by the implantation of a silicone rod for 2 weeks in C57BL/6J diabetic mice. Diabetic mice transplanted with islets into the unmodified subcutaneous space (USS) were used as the controls. After transplantation, nonfasting blood glucose levels were monitored for 8 weeks, and an intraperitoneal glucose tolerance test and histological evaluation were performed. RESULTS: Five of the 10 recipients in the PSS group and two of the nine recipients in the USS group returned to normoglycemia. Engraftment of the transplanted islets was detected in nine of the 10 recipients in the PSS group, and the engraftment rate in the PSS group was significantly higher than that in the USS group (P = .005). Intraperitoneal glucose tolerance test results showed that the glucose tolerance of recipient mice in the PSS group was significantly better than that of the diabetic mice. Histological analysis revealed that the density of capillary vessels in the connective tissue surrounding the engrafted islets in the PSS group was significantly higher than that in the USS group (41.7/mm2 vs 7.2/mm2, P < .01). CONCLUSION: Islet transplantation into the PSS using in-body tissue architecture technology has the potential to improve graft survival.

    DOI: 10.1016/j.transproceed.2025.05.019

    PubMed

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  • [Development of Oncolytic Viruses against Cancer]. Invited Reviewed

    Hiroshi Tazawa, Shinji Kuroda, Shunsuke Kagawa, Toshiyoshi Fujiwara

    Gan to kagaku ryoho. Cancer & chemotherapy   52 ( 6 )   431 - 437   2025.6

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    Authorship:Lead author, Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)  

    Oncolytic virotherapy is a novel antitumor therapy using genetically modified oncolytic viruses(OVs)that specifically replicate and induce lytic cell death in tumor cells. OVs directly induce tumor cell death and indirectly enhance the antitumor efficacy of chemoradiotherapy by suppressing cell survival signaling. Moreover, OVs activate antitumor immunity by inducing immunogenic cell death and enhance the antitumor effect of immune checkpoint inhibitors. OVs including herpes simplex virus and adenovirus have been widely developed for clinical application. This review focuses on the therapeutic potential of OVs in monotherapy and combination therapy with conventional cancer treatment and summarizes representative OVs that are in the phases of clinical trials.

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  • Osteosarcoma cell-derived CCL2 facilitates lung metastasis via accumulation of tumor-associated macrophages. Reviewed International journal

    Hiroya Kondo, Hiroshi Tazawa, Tomohiro Fujiwara, Aki Yoshida, Miho Kure, Koji Demiya, Nobuhiko Kanaya, Toshiaki Hata, Koji Uotani, Joe Hasei, Toshiyuki Kunisada, Shunsuke Kagawa, Yusuke Yoshioka, Toshifumi Ozaki, Toshiyoshi Fujiwara

    Cancer immunology, immunotherapy : CII   74 ( 7 )   193 - 193   2025.5

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    Osteosarcoma (OS) is the most common malignant tumor of bone in children and adolescents. Although lung metastasis is a major obstacle to improving the prognosis of OS patients, the underlying mechanism of lung metastasis of OS is poorly understood. Tumor-associated macrophages (TAMs) with M2-like characteristics are reportedly associated with lung metastasis and poor prognosis in OS patients. In this study, we investigated the metastasis-associated tumor microenvironment (TME) in orthotopic OS tumor models with non-metastatic and metastatic OS cells. Non-metastatic and metastatic tumor cells derived from mouse OS (Dunn and LM8) and human OS (HOS and 143B) were used to analyze the TME associated with lung metastasis in orthotopic OS tumor models. OS cell-derived secretion factors were identified by cytokine array and enzyme-linked immunosorbent assay (ELISA). Orthotopic tumor models with metastatic LM8 and 143B cells were analyzed to evaluate the therapeutic potential of a neutralizing antibody in the development of primary and metastatic tumors. Metastatic OS cells developed metastatic tumors with infiltration of M2-like TAMs in the lungs. Cytokine array and ELISA demonstrated that metastatic mouse and human OS cells commonly secreted CCL2, which was partially encapsulated in extracellular vesicles. In vivo experiments demonstrated that while primary tumor growth was unaffected, administration of CCL2-neutralizing antibody led to a significant suppression of lung metastasis and infiltration of M2-like TAMs in the lung tissue. Our results suggest that CCL2 plays a crucial role in promoting the lung metastasis of OS cells via accumulation of M2-like TAMs.

    DOI: 10.1007/s00262-025-04051-x

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  • HIF-PH inhibitors induce pseudohypoxia in T cells and suppress the growth of microsatellite stable colorectal cancer by enhancing antitumor immune responses. Reviewed International journal

    Yuehua Chen, Toshiaki Ohara, Yusuke Hamada, Yuze Wang, Miao Tian, Kazuhiro Noma, Hiroshi Tazawa, Masayoshi Fujisawa, Teizo Yoshimura, Akihiro Matsukawa

    Cancer immunology, immunotherapy : CII   74 ( 7 )   192 - 192   2025.5

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    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Recent studies have revealed that CD8+ T cells can be activated via genetic upregulation of HIF-1α, thereby augmenting antitumor effector functions. HIF-1α upregulation can be attained by inhibiting HIF-prolyl hydroxylase (HIF-PH) under normoxic conditions, termed pseudohypoxia. This study investigated whether pseudohypoxia induced by HIF-PH inhibitors suppresses Microsatellite stable (MSS) colorectal cancer (CRC) by affecting tumor immune response. METHODS: The HIF-PH inhibitors Roxadustat and Vadadustat were utilized in this study. In vitro, we assessed the effects of HIF-PH inhibitors on human and murine colon cancer cell lines (SW480, HT29, Colon26) and murine T cells. In vivo experiments were performed with mice bearing Colon26 tumors to evaluate the effect of these inhibitors on tumor immune responses. Tumor and spleen samples were analyzed using immunohistochemistry, RT-qPCR, and flow cytometry to elucidate potential mechanisms. RESULTS: HIF-PH inhibitors demonstrated antitumor effects in vivo but not in vitro. These inhibitors enhanced the tumor immune response by increasing the infiltration of CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs). HIF-PH inhibitors induced IL-2 production in splenic and intratumoral CD4+ T cells, promoting T cell proliferation, differentiation, and immune responses. Roxadustat synergistically enhanced the efficacy of anti-PD-1 antibody for MSS cancer by increasing the recruitment of TILs and augmenting effector-like CD8+ T cells. CONCLUSION: Pseudohypoxia induced by HIF-PH inhibitors activates antitumor immune responses, at least in part, through the induction of IL-2 secretion from CD4+ T cells in the spleen and tumor microenvironment, thereby enhancing immune efficacy against MSS CRC.

    DOI: 10.1007/s00262-025-04067-3

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  • [Development of Oncolytic Virus Immunotherapy to Improve the Immunosuppressive Microenvironment in Pancreatic Cancer]. Invited Reviewed

    Kanto Suemori, Hiroshi Tazawa, Motohiko Yamada, Naohiro Okada, Satoru Kikuchi, Shinji Kuroda, Kazuhiro Noma, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara

    Gan to kagaku ryoho. Cancer & chemotherapy   52 ( 5 )   399 - 401   2025.5

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    Immunotherapy resistance in pancreatic ductal adenocarcinoma(PDAC)limits treatment outcomes; therefore, improving the immunosuppressive microenvironment is important for PDAC treatment. We developed an oncolytic adenovirus, OBP-702, carrying the tumor suppressor gene p53, and report its therapeutic potential to induce cytopathic effects and activate antitumor immunity via p53 induction. In the present study, we investigated the therapeutic potential of epigenetic modulators in oncolytic viral immunotherapy combined with a dendritic cell vaccine.

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Books

  • 分子細胞治療フロンティア2025

    田澤大, 黒田新士, 菊地覚次, 垣内慶彦, 金谷信彦, 橋本将志, 浦田泰生, 香川俊輔, 藤原俊義( Role: Joint author ,  膵臓がんの免疫療法抵抗性を克服するp53武装化腫瘍融解ウイルス療法の開発)

    外科分子細胞治療研究会  2025.4  ( ISBN:9784991346613

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  • 入門腫瘍内科学 改訂第4版

    田澤大( Role: Contributor ,  E 新規治療 1) ウイルス療法, 2) 光免疫療法)

    日本臨床腫瘍学会  2025.3 

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  • 分子細胞治療フロンティア 2020

    香川俊輔, 野間和広, 田澤 大, 藤原俊義( Role: Joint author ,  がん治療の新たなmodalityとしての近赤外線光免疫療法)

    外科分子細胞治療研究会  2020.4  ( ISBN:9784990253196

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    Total pages:243p   Language:Japanese

    CiNii Books

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  • 分子細胞治療フロンティア 2020

    黒田新士, 金谷信彦, 田澤 大, 浦田泰生, 藤原俊義( Role: Joint author ,  テロメラーゼ特異的腫瘍融解アデノウイルス製剤の臨床開発と今後の展望)

    外科分子細胞治療研究会  2020.4  ( ISBN:9784990253196

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    Total pages:243p   Language:Japanese

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  • いま、本格化する遺伝子治療 遺伝性疾患・がんと戦う新たな一手(実験医学 増刊)

    藤原俊義, 田澤 大, 田邊俊介, 白川靖博( Role: Joint author ,  食道がんに対する放射線併用遺伝子組換えウイルス療法)

    羊土社  2020.2 

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MISC

  • Pseudohypoxia by HIF-PHD inhibitors activates tumor immune response for MSS colorectal cancer.

    Toshiaki Ohara, Yuehua Chen, Yusuke Hamada, Hajime Kashima, Satoru Kikuchi, Kazuhiro Noma, Hiroshi Tazawa, Masayoshi Fujisawa, Toshiyoshi Fujiwara, Akihiro Matsukawa

    CANCER SCIENCE   116   663 - 663   2025.1

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    Language:English   Publishing type:Research paper, summary (international conference)  

    Web of Science

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  • 腫瘍融解アデノウイルス製剤の免疫賦活薬としての有用性と免疫チェックポイント阻害剤との複合免疫療法の可能性

    黒田新士, 金谷信彦, 橋本将志, 垣内慶彦, 菊地覚次, 田澤大, 香川俊輔, 藤原俊義

    日本外科学会定期学術集会(Web)   125th   2025

  • RNA編集酵素ADAR1に基づく大腸癌肝転移の残肝再発リスク層別化の検討

    高橋 利明, 重安 邦俊, 中村 峻輔, 高橋 政史, 萱野 真史, 新田 薫, 森分 和也, 安井 和也, 松三 雄騎, 藤 智和, 近藤 喜太, 寺石 文則, 田澤 大, 藤原 俊義

    日本癌治療学会学術集会抄録集   62回   P80 - 2   2024.10

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    Language:English   Publisher:(一社)日本癌治療学会  

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  • 潰瘍性大腸炎においてRNA編集解析が発癌予測バイオマーカーとなりうる

    森分 和也, 重安 邦俊, 萱野 真史, 新田 薫, 中村 峻輔, 高橋 利明, 高橋 政史, 金谷 信彦, 松三 雄騎, 近藤 喜太, 寺石 文則, 田澤 大, 藤原 俊義

    日本癌治療学会学術集会抄録集   62回   P43 - 2   2024.10

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    Language:English   Publisher:(一社)日本癌治療学会  

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  • FAPを標的とした近赤外線光免疫療法によるCAF-rich腫瘍への化学療法抵抗性の克服

    西村 星多郎, 野間 和広, 松本 佑, 竹田 泰茂, 高橋 達也, 松本 聖, 河崎 健人, 國友 知義, 賀島 肇, 加藤 卓也, 菊地 覚次, 大原 利章, 田澤 大, 藤原 俊義

    日本癌治療学会学術集会抄録集   62回   O76 - 2   2024.10

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Awards

  • がん研究奨励賞

    2013.6   岡山医学会  

    田澤 大

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  • アンジェスMG賞

    2012.6   日本遺伝子治療学会  

    田澤 大

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  • とやま賞(医薬部門)

    2010.5   財団法人 富山県ひとづくり財団  

    田澤 大

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  • 優秀発表賞

    2007.9   日本疾患モデル学会  

    田澤 大

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Research Projects

  • 原発性脊椎腫瘍に対する腫瘍融解ウイルス療法の確立

    Grant number:24K12352  2024.04 - 2027.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    鷹取 亮, 吉田 晶, 小田 孔明, 魚谷 弘二, 篠原 健介, 藤原 智洋, 田澤 大

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    Grant amount:\4550000 ( Direct expense: \3500000 、 Indirect expense:\1050000 )

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  • 脊椎脊髄腫瘍に対する腫瘍融解ウイルス療法の確立

    Grant number:23K08589  2023.04 - 2026.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    魚谷 弘二, 吉田 晶, 尾崎 敏文, 藤原 智洋, 田澤 大, 三澤 治夫, 小田 孔明

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    Grant amount:\4810000 ( Direct expense: \3700000 、 Indirect expense:\1110000 )

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  • Immune molecular mechanism for enhancing antitumor potency of a next-generation oncolytic virus by pre-immunization

    Grant number:22H03148  2022.04 - 2025.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    藤原 俊義, 田澤 大, 黒田 新士

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    Grant amount:\17680000 ( Direct expense: \13600000 、 Indirect expense:\4080000 )

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  • Exploration of metabolic factors to inhibit tumor-specific p53 gene therapy in pancreatic cancer

    Grant number:21K07219  2021.04 - 2024.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    田澤 大

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    Grant amount:\4160000 ( Direct expense: \3200000 、 Indirect expense:\960000 )

    遺伝子変異に応じたゲノム医療は癌患者に最適な個別化治療を提供することが期待されている。しかし、KRAS/p53変異膵臓癌への治療法は未だ確立していない。申請者は癌特異的にp53を誘導するアデノウイルス製剤OBP-702を開発し、KRAS/p53変異膵臓癌細胞の腫瘍増殖を抑制することを明らかにし、臨床応用を進めている。しかし、膵臓癌細胞には解糖系と非解糖系の代謝サブタイプが存在し、アデノウイルスに対する感受性が代謝サブタイプによって異なることが示唆されている。
    本研究では、解糖系と非解糖系のヒト膵臓癌細胞を用いてOBP-702に対する感受性を阻害する代謝関連因子を網羅的に解析し、代謝調節剤を併用することでOBP-702抵抗性を改善する最適なOBP-702個別化治療の開発を行う。
    令和3年度は、解糖系のヒト膵臓癌細胞株2種類(MIAPaCa-2、PK-45H)と非解糖系のヒト膵臓癌細胞株2種類(PK-59、Capan-2)における代謝関連因子の発現をウェスタンブロット法で解析し、解糖系のヒト膵臓癌細胞は非解糖系に比べてLDHA、IDH1、GOT1の発現レベルが高いことを確認した。次に、OBP-702に対する感受性をXTTアッセイで解析し、解糖系のヒト膵臓癌細胞は非解糖系に比べてウイルス感受性が高いことを確認した。ウイルス感受性の違いはp53非搭載型のアデノウイルス製剤OBP-301でも同様の結果であった。ウイルス感受性の違いのメカニズムを明らかにするために、細胞表面のウイルス受容体やインテグリンの発現をFACS法で解析したが、大きな違いは認めなかった。一方、ウイルス感染後のE1Aの発現をウェスタンブロット法で解析し、解糖系のヒト膵臓癌細胞は非解糖系に比べてE1Aの発現レベルが高いことを確認した。以上より、代謝関連因子がウイルスの複製効率に大きく関与している可能性が示唆された。

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  • Development of a next-generation viral agent targeting immunosuppression by crosstalk in the pancreatic cancer microenvironment

    Grant number:19H03731  2019.04 - 2022.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Fujiwara Toshiyoshi

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    Grant amount:\17550000 ( Direct expense: \13500000 、 Indirect expense:\4050000 )

    We examined the effect of OBP-702, a next-generation armed adenovirus OBP-702, which carries the multifunctional tumor suppressor p53 gene, on the immunosuppressive pancreatic cancer microenvironment. Pancreatic cancer stromal cells (human pancreatic stellate cells: hPSC) promoted tumor growth by coexisting with pancreatic cancer cells in the pancreatic cancer microenvironment, and OBP-702 produced strong p53 gene expression in hPSC. By inducing selective apoptosis, in addition to the antitumor effect on the pancreatic cancer cells, OBP-702 exhibited a profound antitumor activity through the control of the pancreatic cancer microenvironment.

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Class subject in charge

  • Practicals: Gastroenterological Surgery (2024academic year) special  - その他

  • Research Projects: Gastroenterological Surgery (2024academic year) special  - その他

  • Research Projects and Practicals: Gastroenterological Surgery I (2024academic year) special  - その他

  • Lecture and Research Projects: Gastroenterological Surgery I (2024academic year) special  - その他

  • Research Projects and Practicals: Gastroenterological Surgery II (2024academic year) special  - その他

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