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Faculty of Medicine School of Medicine Department of Internal Medicine, Hematology, Diabetes, and Endocrinology |
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SHIMODA Kazuya
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Degree 【 display / non-display 】
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博士（医学） ( 1994.5 九州大学 )
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医学士 ( 1987.3 九州大学 )
Research Areas 【 display / non-display 】
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Life Science / Hematology and medical oncology
Papers 【 display / non-display 】
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Fauzi Y.R., Nakahata S., Shimoda K., Matsuura T., Hagiwara S., Inoue K., Moritake H., Morishita K.
Biochemical and Biophysical Research Communications 756 151564 2025.4
Language：English Publishing type：Research paper (scientific journal) Publisher：Biochemical and Biophysical Research Communications
Previously, we developed a complete human IgG TFR1 antibody (JST-TFR09/PPMX-T003) that showed a potentially practical therapeutic effect against adult T-cell leukemia/lymphoma (ATLL) in vitro and in vivo. In the present study, to elucidate the molecular mechanism underlying ATLL cell death induced by anti-TFR1 antibodies, we performed comprehensive gene expression analysis and mass spectrometry on ATLL cells treated with PPMX-T003 antibody. These results suggest that PPMX-T003 antibody treatment of ATLL cell lines induces ferroptosis mediated by ferritin degradation. PPMX-T003 antibody-treated ATLL cell lines showed a decrease in ferritin proteins, an increase in ferrous iron (Fe2+), reactive oxygen species (ROS) generation, and malondialdehyde as induction of lipid peroxidation. Moreover, treatment with a ferroptosis inhibitor (ferroportin-1) inhibited the cell death induced by PPMX-T003 antibody in ATLL cells. Furthermore, NCO4A and LC3-II were induced following antibody treatment, and ferritin degradation was inhibited by lysosomal inhibitors, suggesting that ferritin degradation depends on autolysosomal system activation. Here, we introduce ferroptosis as one of the potential mechanisms of PPMX-T003 antibody, which is promising for future therapeutic antibodies targeting a wide range of leukemia and cancers, including ATLL.
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Effects of tucidinostat in adult T-cell leukemia/lymphoma in clinical practice Reviewed
Kamiunten A., Kameda T., Sekine M., Kawano H., Toyama T., Akizuki K., Kawano N., Maeda K., Sato S., Takeuchi M., Ishizaki J., Nagamine K., Kuroki A., Ikeda R., Matsumoto K., Karasawa M., Tahira Y., Uchida T., Shimoda H., Hidaka T., Yamashita K., Yamaguchi H., Kubuki Y., Shimoda K., Shide K.
International Journal of Hematology 2025.3
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy with a poor prognosis. We conducted a retrospective study across six institutions in Miyazaki Prefecture, Japan, to assess the efficacy of tucidinostat in patients with relapsed/refractory ATL who had not undergone transplantation. Between October 2021 and July 2023, 24 patients aged 41 to 88 years (median, 73.4 years) who had undergone prior therapies, including intensive chemotherapy (79.2%) and mogamulizumab immunotherapy (79.2%), received tucidinostat. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated as key outcomes. ORR and DCR reached 54.2% and 91.7%, respectively. The median PFS was 3.95 months, and OS was 8.04 months, which were not inferior to the results of a phase IIb study. The influential factors for PFS were age ≥ 75 years and high soluble IL-2 receptor (sIL-2R) levels above 5000 U/mL at the start of treatment. Favorable patients without these factors achieved a PFS of 11.4 months. Treatment-related adverse events were mainly hematologic but were managed over the course of treatment. Our findings indicate that tucidinostat provides survival benefits in patients with relapsed/refractory ATL in clinical practice and highlight key clinical factors for better outcomes.
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Takahashi N., Takenaka K., Iriyama N., Kirito K., Kawaguchi T., Kimura S., Shimoda K.
International Journal of Hematology 121 ( 1 ) 5 - 38 2025.1
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
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Yoshikawa N., Ehara Y., Yamada Y., Matsusaki Y., Shimoda K., Ikeda R.
Scientific Reports 15 ( 1 ) 3364 2025.1
Language：English Publishing type：Research paper (scientific journal) Publisher：Scientific Reports
Intra-patient variability in immunosuppressive blood drug concentrations is a potential biomarker in managing organ transplant patients. However, the association between the time in therapeutic range of tacrolimus blood concentrations and its efficacy in preventing graft-versus-host disease remains unknown. In this study, we analyzed the relationship between the time in therapeutic range of tacrolimus blood concentrations and its efficacy in acute graft-versus-host disease prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation. Eligible patients administered tacrolimus were categorized into two groups based on the grade of acute graft-versus-host disease, and propensity score matching was performed using graft-versus-host disease prophylaxis protocols and days to the disease onset to compare time in therapeutic range. In patients with tacrolimus blood concentration therapeutic range ≥ 10 ng/mL, time in therapeutic range during the first 4 weeks post-transplantation was significantly lower in the Grade II–III than in the Grade 0–I group. Among propensity score matching-extracted patients, the Grade II–III group had significantly lower time in therapeutic range during the first 2 and 4 weeks post-transplantation. Our results suggest that high time in therapeutic range early post-transplantation, particularly within 4 weeks, may avert the severity of acute graft-versus-host disease.
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C-Mannosyl tryptophan is a novel biomarker for thrombocytosis of myeloproliferative neoplasms Reviewed
Tabata S., Yamashita Y., Inai Y., Morita S., Kosako H., Takagi T., Shide K., Manabe S., Matsuoka T.A., Shimoda K., Sonoki T., Ihara Y., Tamura S.
Scientific Reports 14 ( 1 ) 18858 2024.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Scientific Reports
C-Mannosyl tryptophan (CMW), a unique glycosylated amino acid, is considered to be produced by degradation of C-mannosylated proteins in living organism. Although protein C-mannosylation is involved in the folding and secretion of substrate proteins, the pathophysiological function in the hematological system is still unclear. This study aimed to assess CMW in the human hematological disorders. The serum CMW levels of 94 healthy Japanese workers were quantified using hydrophilic interaction liquid chromatography. Platelet count was positively correlated with serum CMW levels. The clinical significance of CMW in thrombocytosis of myeloproliferative neoplasms (T-MPN) including essential thrombocythemia (ET) were investigated. The serum CMW levels of the 34 patients with T-MPN who presented with thrombocytosis were significantly higher than those of the 52 patients with control who had other hematological disorders. In patients with T-MPN, serum CMW levels were inversely correlated with anemia, which was related to myelofibrosis (MF). Bone marrow biopsy samples were obtained from 18 patients with ET, and serum CMW levels were simultaneously measured. Twelve patients with bone marrow fibrosis had significantly higher CMW levels than 6 patients without bone marrow fibrosis. Collectively, these results suggested that CMW could be a novel biomarker to predict MF progression in T-MPN.
Books 【 display / non-display 】
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WHO分類第5版による白血病・リンパ系腫瘍の病態学
久冨木庸子、下田和哉 他（ Role： Contributor , 骨髄性／リンパ性腫瘍）
中外医学社 2024.12
Book type：Scholarly book
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イヤーノート2025 内科・外科編
下田和哉 他（ Role： Joint author , 血液学総論（造血幹細胞移植~脾摘術）、白血球系の異常(白血球増加症～骨髄異形成症候群)、白血球系の異常（悪性リンパ腫以外の成熟B細胞腫瘍～成熟T細胞腫瘍））
株式会社メディックメディア 2024.3
Book type：Scholarly book
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別冊日本臨牀 血液症候群（第3版）ーその他の血液疾患を含めてーⅣ
亀田拓郎、幣光太郎、下田和哉（ Role： Joint author , 本態性血小板血症）
株式会社 日本臨牀社 2024.2
Responsible for pages：27-32頁 Language：Japanese Book type：Scholarly book
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血液専門医テキスト(改訂第4版)
下田和哉 他（ Role： Joint author , その他の骨髄増殖性疾患 252-254頁）
株式会社 南江堂 2023.10
Language：Japanese Book type：Textbook, survey, introduction
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造血器腫瘍診療ガイドライン2023年版
下田和哉、入山規良、川口辰哉、木村晋也、桐戸敬太、髙橋直人、竹中克斗（ Role： Joint author , 慢性骨髄性白血病/骨髄増殖性腫瘍（chronic myeloid leukemia/myeloproliferative neoplasms:CML/MPN））
金原出版 2023.7 （ ISBN:978-4-307-10224-7 ）
Total pages：484 Responsible for pages：50 Book type：Scholarly book
MISC 【 display / non-display 】
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【白血病・リンパ腫 臨床現場で役立つ白血病・リンパ腫の最新の知識】さまざまな白血病・リンパ腫病型における診療のポイント 骨髄増殖性腫瘍の診断と治療
亀田拓郎、下田和哉：
Medical Practice 42 ( 2 ) 219 - 223 2025.2
Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
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【アンメットニーズに対するJAK阻害薬の可能性】骨髄増殖性腫瘍に対するJAK阻害薬の治療効果
幣光太郎、下田和哉
炎症と免疫 32 ( 2 ) 129 - 132 2024.2
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
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治療法の再整理とアップデートのために 専門家による私の治療 原発性骨髄線維症(PMF)
下田和哉
日本医事新報 ( 5203 ) 34 - 35 2024.1
Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
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【JAK阻害薬の効果・安全性と展望】骨髄線維症,真性多血症の病態と,JAK阻害薬の効果・安全性・展望
幣光太郎、下田和哉
リウマチ科 70 ( 6 ) 608 - 614 2023.12
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
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【実診療において治療に難渋する造血器腫瘍の病態と新たな治療戦略】二次性骨髄線維症の治療 新規治療薬開発の動向も踏まえて
秋月渓一、下田和哉
血液内科 87 ( 2 ) 193 - 198 2023.8
Publishing type：Rapid communication, short report, research note, etc. (scientific journal)
Presentations 【 display / non-display 】
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Phase I Safety Study of Anti-Transferrin Receptor 1 Antibody (PPMX-T003) in Patients with Polycythemia Vera and Erythrocythemia. International conference
Tomoki Ito, MD, PhD ,Teruhito Takakuwa, MD, PhD , Masayuki Hino, MD, PhD , Hirohisa Nakamae, MD, PhD , Kazunori Murai, MD, PhD , Yoko Kubuki, MD, PhD , Kazuya Shimoda, M.D., Ph.D. , Yuji Kumagai, MD, PhD , Yukiya Yamamoto, MD, PhD and Tadashi Matsuura, PhD:
The American society of Hematology 66th Annual Meeting and Exposition 2024.12.9
Event date： 2024.12.7 - 2024.12.10
Presentation type：Oral presentation (general)
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1805 Impact of Cooperating Myeloid Gene Mutations on Disease Progression and Survival in Japanese MPN Patients: A Multicenter Study. International conference
Saki Ogawa, Kotaro Shide, Masami Takeuchi, Kosei Matsue, Takuro Kameda, Masato Yasumi, Takahiro Karasuno, Taizo Shimomura, Hitoshi Suzushima, Kiyoshi Yamashita, Noriaki Kawano, Osamu Imataki, Norimitsu Kadowaki, Akihito Yonezawa, Eiichi Otsuka, Yoshio Saburi, Yuki Tahira, Ayako Kamiunten, Keiichi Akizuki, Masayoshi Karasawa, Ryoma Ikeda, Kengo Matsumoto, Ayuka Kuroki, Koshiro Nagamine, Yoko Kubuki, Kazuya Shimoda:
The American society of Hematology 66th Annual Meeting and Exposition 2024.12.7
Event date： 2024.12.7 - 2024.12.10
Presentation type：Poster presentation
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腸内細菌叢に由来するコハク酸セミアルデヒドは ATL 細胞の増殖を促進する
千葉 のどか、鈴木 真也、Enriquez-Vera Daniel、宇都宮 與、久冨木 庸子、日髙 智徳、下田 和哉、中畑 新吾、山田 拓司、森下 和広
第10回日本HTLV-1学会学術集会 (東京都) 2024.11.9 東京大学大学院 新領域創成科学研究科 病態医療科学分野
Event date： 2024.11.8 - 2024.11.10
Presentation type：Oral presentation (general)
Venue：東京都
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宮崎県における再発/難治性 ATL に対する Valemetostat 療法の治療効果
上運天 綾子、亀田 拓郎、長嶺 宏士朗、黒木 安優香、池田 涼馬、松本 健吾、秋月 渓一、関根 雅明、河野 浩、久冨木 庸子、山下 清、外山 孝典、佐藤 誠一、前田 宏一、石崎 淳三、下田 和哉
第10回日本HTLV-1学会学術集会 (東京都) 2024.11.10 東京大学大学院 新領域創成科学研究科 病態医療科学分野
Event date： 2024.11.8 - 2024.11.10
Presentation type：Oral presentation (general)
Venue：東京都
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HTLV-1 キャリアにおける新型コロナウイルスワクチン接種回数の最適化
亀田 拓郎、宇都宮 與、中野 伸亮、徳永 雅仁、宮園 卓宜、伊藤 能清、米倉 健太郎、日髙 道弘、河北 敏郎、幣 光太郎、田平 優貴、秋月 渓一、上運天 綾子、久冨木 庸子、下田 和哉
第10回日本HTLV-1学会学術集会 (東京都) 2024.11.9 東京大学大学院 新領域創成科学研究科 病態医療科学分野
Event date： 2024.11.8 - 2024.11.10
Presentation type：Poster presentation
Venue：東京都
Awards 【 display / non-display 】
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日本白血病研究基金 清水賞
2002.11 日本白血病研究基金
下田和哉
Award type：Award from publisher, newspaper, foundation, etc. Country：Japan
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日本癌学会奨励賞
2002.10 日本がん学会
下田和哉
Award type：Award from Japanese society, conference, symposium, etc. Country：Japan
Grant-in-Aid for Scientific Research 【 display / non-display 】
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新規病態：HTLV-1陽性HRS細胞を伴う成人T細胞白血病/リンパ腫の統合的解析
Grant number：23K27384 2023.04 - 2027.03
独立行政法人日本学術振興会 科学研究費基金 基盤研究(B)
Authorship：Coinvestigator(s)
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新規病態：HTLV-1陽性HRS細胞を伴う成人T細胞白血病/リンパ腫の統合的解析
Grant number：23H02693 2023.04 - 2027.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(B)
Authorship：Coinvestigator(s)
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腫瘍性fibrocyteの本態解明と、骨髄線維症診断・治療への展開
Grant number：23K27629 2023.04 - 2026.03
独立行政法人日本学術振興会 科学研究費基金 基盤研究(B)
Authorship：Principal investigator
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腫瘍性fibrocyteの本態解明と、骨髄線維症診断・治療への展開
Grant number：23H02938 2023.04 - 2026.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(B)
Authorship：Principal investigator
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1007創薬に向けた、CALR変異とfibrocyteに着目する骨髄増殖性腫瘍研究
Grant number：17H04210 2017.04 - 2019.03
科学研究費補助金 基盤研究(B)
下田和哉、久冨木庸子、日髙智徳、幣光太郎
Authorship：Principal investigator
骨髄増殖性腫瘍(MPN)のドライバー変異であるJAK2,CALR変異が同定されMPNの病態が明らかにされつつあるが、CALR変異がMPNを発症させる機序や、骨髄線維症の本態である骨髄線維化細胞の起源、つまり間質の反応性変化なのか、あるいは腫瘍クローン由来fibrocyteなのかは不明である。本研究では以下の3つの方法により、MPNの新たな治療につながる研究を行う。
Ⅰ. MPLとの会合やSTAT活性化に必須な変異CALRの領域同定と、その阻害による治療開発
Ⅱ. 本態性血小板血症から骨髄線維症へ進展する分子イベントの同定
Ⅲ. 腫瘍クローン由来fibrocyteが骨髄線維化に果たす役割の同定と、骨髄線維化を改善することをすでに見出しているMEK阻害剤がfibrocyteに及ぼす影響の解明
Past consigned research fund received 【 display / non-display 】
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A Phase 2b Open-Label Single-Arm Study to Evaluate the Efficacy and Safety of Oral HBI-8000 in Patients with Relapsed or Refractory Adult T Cell Lymphoma(ATL)
2017.01 - 2019.12
Investigational New Drug Test
Consigned research type：Investigational New Drug Test
Available Technology 【 display / non-display 】
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骨髄増殖性腫瘍、病因遺伝子の機能解析と新規治療法開発
白血病細胞のゲノム情報に基づく成人T細胞白血病の克服戦略Home Page： 内科学講座 血液・糖尿病・内分泌学分野
Related fields where technical consultation is available：・血液疾患マウスモデルの作成と解析、治療法開発への応用
・サイトカインシグナル伝達機構の解析
（共同研究が可能なテーマ）骨髄増殖性腫瘍、成人T細胞白血病を対象とした研究