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Affiliation |
Faculty of Medicine School of Medicine Department of Internal Medicine, Hematology, Diabetes, and Endocrinology |
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Professor |
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External Link |
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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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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.
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Clinical characteristics in adolescents and young adults with polycythemia vera and essential thrombocythemia in Japan. Reviewed
Sugimoto Y, Nagaharu K, Ohya E, Ohishi K, Tawara I, Ito T, Gotoh A, Nakamae M, Kimura F, Koike M, Kirito K, Wada H, Usuki K, Tanaka T, Mori T, Wakita S, Saito TI, Saito AM, Shimoda K, Kurokawa T, Tomita A, Edahiro Y, Hashimoto Y, Kiyoi H, Akashi K, Matsumura I, Takenaka K, Komatsu N
International journal of hematology 2024.10
Language：English Publishing type：Research paper (scientific journal)
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Abu-Zeinah G., Qin A., Gill H., Komatsu N., Mascarenhas J., Shih W.J., Zagrijtschuk O., Sato T., Shimoda K., Silver R.T., Mesa R.
Annals of Hematology 103 ( 9 ) 3573 - 3583 2024.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Annals of Hematology
Primary myelofibrosis (PMF) is the most aggressive of the myeloproliferative neoplasms and patients require greater attention and likely require earlier therapeutic intervention. Currently approved treatment options are limited in their selective suppression of clonal proliferation resulting from driver- and coexisting gene mutations. Janus kinase inhibitors are approved for symptomatic patients with higher-risk PMF. Additionally, most ongoing clinical studies focus on patients with higher-risk disease and/or high rates of transfusion dependency. Optimal treatment of early/lower-risk PMF remains to be identified and needs randomized clinical trial evaluations. Pegylated interferon alfa is recommended for symptomatic lower-risk PMF patients based on phase 2 non-randomized studies and expert opinion. Ropeginterferon alfa-2b (ropeg) is a new-generation pegylated interferon-based therapy with favorable pharmacokinetics and safety profiles, requiring less frequent injections than prior formulations. This randomized, double-blind, placebo-controlled phase 3 trial will assess its efficacy and safety in patients with “early/lower-risk PMF”, defined as pre-fibrotic PMF or PMF at low or intermediate-1 risk according to Dynamic International Prognostic Scoring System-plus. Co-primary endpoints include clinically relevant complete hematologic response and symptom endpoint. Secondary endpoints include progression- or event-free survival, molecular response in driver or relevant coexisting gene mutations, bone marrow response, and safety. Disease progression and events are defined based on the International Working Group criteria and well-published reports. 150 eligible patients will be randomized in a 2:1 ratio to receive either ropeg or placebo. Blinded sample size re-estimation is designed. Ropeg will be administered subcutaneously with a tolerable, higher starting-dose regimen. The study will provide important data for the treatment of early/lower-risk PMF for which an anti-clonal, disease-modifying agent is highly needed.
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Nagaharu K., Ohya E., Edahiro Y., Hashimoto Y., Ito T., Gotoh A., Nakamae M., Kimura F., Koike M., Kirito K., Wada H., Usuki K., Tanaka T., Mori T., Wakita S., Saito T.I., Saito A.M., Shimoda K., Kurokawa T., Tomita A., Kiyoi H., Akashi K., Matsumura I., Takenaka K., Komatsu N., Ohishi K., Tawara I., Sugimoto Y.
Annals of Hematology 103 ( 9 ) 3535 - 3541 2024.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Annals of Hematology
Thrombosis in myeloproliferative neoplasms (MPNs) is an important clinical problem, and risk-stratified management is essential. To identify the clinical characteristics of thrombosis in patients with MPNs, a nationwide multi-institutional retrospective analysis (JSH-MPN-R18) was conducted. The aim of the present study was to perform a sub-analysis of JSH-MPN-R18 findings to clarify the predictive parameters for thrombosis among complete blood count (CBC) results. Among the patients enrolled in JSH-MPN-R18, those with essential thrombocythemia (ET; n = 1152) and polycythemia vera (PV; n = 456) were investigated. We analyzed and compared CBC parameters between patients with and those without any thrombotic events using Welch’s T-test. Statistical analyses were performed using the R statistical software. Thrombotic events were observed in 74 patients with ET. In multivariate analysis, only the neutrophil ratio was slightly but significantly higher for ET patients with thrombosis than for those without (p < 0.05). Of note, the absolute neutrophil count (aNeu) was considered a useful predictive tool for thrombosis among patients classified as low-risk according to the revised International Prognostic Score of Thrombosis for Essential Thrombocythemia. Among PV patients, those with thrombosis showed significantly higher hematocrit and aNeu than did those without thrombosis. As a thrombosis-associated factor, the neutrophil ratio was slightly but significantly elevated in patients with ET. This myeloid skew might reflect a higher value of JAK2 V617F allelic frequency in patients with ET with thrombosis; this was not clarified in JSH-MPN-R18. Further accumulation of evidence, including genetic information for JAK2 and other passenger mutations, is warranted.
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Shimoda K., Komatsu N., Matsumura I., Ikeda K., Hino M., Hidaka M., Maeda Y., Kondo T., Fujisaki T., Shoshi K., Azuma K., Fukushima R., Kawashima J., Kosugi H.
International Journal of Hematology 120 ( 3 ) 314 - 324 2024.9
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Hematology
Momelotinib, an oral Janus kinase (JAK) 1/2 and activin A receptor type 1 inhibitor, improved symptoms, splenomegaly, and anemia in patients with myelofibrosis (MF). This sub-analysis of SIMPLIFY-1 evaluated the efficacy and safety of momelotinib versus ruxolitinib in Japanese patients with JAK inhibitor (JAKi)-naïve MF. Patients were randomized 1:1 to receive momelotinib 200 mg once daily or ruxolitinib 20 mg twice daily (or modified based on label) for 24 weeks, after which patients could receive open-label momelotinib. The primary endpoint was splenic response rate (SRR; ≥ 35% reduction in spleen volume) at 24 weeks; main secondary endpoints were total symptom score (TSS) response (≥ 50% reduction) and transfusion independence (TI) rates. Fifteen Japanese patients (momelotinib, n = 6; ruxolitinib, n = 9) were enrolled; all completed treatment. At Week 24, SRR was 50.0% with momelotinib and 44.4% with ruxolitinib. TSS response rates were 33.3% and 0%, and TI rates were 83.3% and 44.4%. Any-grade treatment-related adverse event (TRAE) rates were 83.3% with momelotinib and 88.9% with ruxolitinib. Grade 3/4 TRAE rates were 0% and 55.6%, with specific events being anemia (55.6%) and vertigo (11.1%) with ruxolitinib. Momelotinib was well tolerated, improved spleen and symptom responses, and reduced transfusion requirements in Japanese patients with JAKi-naïve MF.
Books 【 display / non-display 】
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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（悪性腫瘍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
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イヤーノート2024 内科・外科編
下田和哉 他（ Role： Contributor , 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、悪性腫瘍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 2023.3
Language：Japanese Book type：Scholarly book
MISC 【 display / non-display 】
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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)
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Uchida T., Ueno H., Konagata A., Taniguchi N., Kogo F., Nagatomo Y., Shimizu K., Yamaguchi H., Shimoda K.
Diabetes Therapy 14 ( 6 ) 1075 - 1076 2023.6
Language：English Publishing type：Rapid communication, short report, research note, etc. (scientific journal) Publisher：Diabetes Therapy
Presentations 【 display / non-display 】
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ネフローゼ症候群を呈した非典型的慢性GVHD
長嶺宏士朗、松本健吾、幣光太郎、秋月渓一、池田涼馬、唐澤賢祥、上運天綾子、田平優貴、亀田拓郎、久冨木庸子、下田和哉
第14回日本血液学会九州地方会 2024.3.9
Event date： 2024.3.9
Presentation type：Oral presentation (general)
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ATL新規治療標的同定と、個別化診療への展開
下田和哉
HTLV-1 関連疾患研究領域 研究班合同発表会 2024.2.17 厚生労働省 新興・再興感染症及び予防接種政策推進研究事業「HTLV-1総合対策」推進におけるキャリア対策の基盤整備と適正な研究開発の推進に資する包括的評価と提言のための研究、AMED
Event date： 2024.2.17
Presentation type：Oral presentation (general)
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NS-018, a potent novel JAK2 inhibitor,effectively treats murine MPN induced by the Janus kinase 2 (JAK2) V617F mutant. International conference
Yuki Tahira, Kotaro Shide, MD, PhD, Takuro Kameda, MD, Ayako Kamiunten, Keiichi Akizuki, MD, Masayoshi Karasawa, Ryoma Ikeda, Kengo Matsumoto, Yoko Kubuki, MD, PhD, Kazuya Shimoda, MD, PhD
The American society of Hematology 65th Annual Meeting and Exposition (San Diego, California, USA) 2023.12.11
Event date： 2023.12.9 - 2023.12.12
Language：English Presentation type：Oral presentation (general)
Venue：San Diego, California, USA Country：United States
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チルゼパチド投与3か月後にインスリン60単位/日を中止できた一例
上野浩晶、水田雅也、古郷芙美子、中村孝之、内田泰介、与那嶺真一、積島愛加理、積島宏昴、清水浩一郎、山口秀樹、下田和哉
第61回日本糖尿病学会九州地方会 2023.12.2
Event date： 2023.12.1 - 2023.12.2
Presentation type：Oral presentation (general)
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２型糖尿病に対するチルゼパチドの短期使用効果の検討
与那嶺真一、上野浩晶、古郷芙美子、中村孝之、内田泰介、積島愛加理、積島宏昴、清水浩一郎、山口秀樹、下田和哉
第61回日本糖尿病学会九州地方会 2023.12.2
Event date： 2023.12.1 - 2023.12.2
Presentation type：Oral presentation (general)
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：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：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 -
TET2変異による造血器腫瘍の発症と進展メカニズムの解明
Grant number：26461408 2014.04 - 2017.03
科学研究費補助金 基盤研究(C)
Authorship：Principal investigator
TET2変異による造血器腫瘍の発症と進展メカニズムの解明
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骨髄増殖性腫瘍における病型の進展と急性転化メカニズムの解明
Grant number：24591401 2012.04 - 2015.03
科学研究費補助金 基盤研究(C)
Authorship：Coinvestigator(s)
骨髄増殖性腫瘍における病型の進展と急性転化メカニズムの解明
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