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写真a

ナカシマ ケンタロウ
中島 健太郎
NAKASHIMA KENTARO
所属
医学研究院 助教
職名
助教
プロフィール
小児科 教育主任

学位

  • 博士(九州大学、日本)

研究テーマ・研究キーワード

  • 研究テーマ:ダウン症候群の免疫異常および造血器疾患の病態解明

    研究キーワード:ダウン症候群, 白血病, 樹状細胞

    研究期間: 2024年4月 - 2026年3月

論文

  • Azacitidine treatment for myeloid leukemia associated with Down syndrome: A nationwide retrospective study in Japan 査読 国際誌

    Kato, S; Nakashima, K; Yamato, G; Saito, S; Taneyama, Y; Yamamoto, N; Miyamura, T; Kato, K; Sato, Y; Yamada, A; Kamiya, T; Nishikawa, T; Uemura, S; Tomizawa, D; Moritake, H; Terui, K; Taga, T; Hasegawa, D

    PEDIATRIC BLOOD & CANCER   71 ( 10 )   e31244   2024年10月   ISSN:1545-5009 eISSN:1545-5017

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    記述言語:英語   出版者・発行元:Pediatric Blood and Cancer  

    Hypomethylating agent treatment for myeloid leukemia associated with Down syndrome (ML-DS) has been scarcely reported. Herein, we collected information on azacitidine treatment for ML-DS in Japan. Forty-eight cycles of azacitidine treatment were performed for 12 patients, including 11 relapsed or refractory (R/R) patients. In 40 cycles, azacitidine was used as monotherapy. No azacitidine-related death was observed. One cycle concurrently administered with methotrexate-based intrathecal therapy was discontinued due to toxicities. Only 4 of the 19 cycles given in non-remission achieved complete or partial remission. In conclusion, although most toxicities were acceptable, azacitidine monotherapy might be insufficient for R/R ML-DS cases.

    DOI: 10.1002/pbc.31244

    Web of Science

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  • The immunoreactive signature of monocyte-derived dendritic cells from patients with Down syndrome 査読 国際誌

    Nakashima, K; Imai, T; Shiraishi, A; Unose, R; Goto, H; Nagatomo, Y; Kojima-Ishii, K; Mushimoto, Y; Nishiyama, K; Yamamura, K; Nagata, H; Ishimura, M; Kusuhara, K; Koga, Y; Sakai, Y; Ohga, S

    CLINICAL AND EXPERIMENTAL IMMUNOLOGY   217 ( 3 )   291 - 299   2024年6月   ISSN:0009-9104 eISSN:1365-2249

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    担当区分:筆頭著者   記述言語:英語   出版者・発行元:Clinical and Experimental Immunology  

    The clinical spectrum of Down syndrome (DS) ranges from congenital malformations to premature aging and early-onset senescence. Excessive immunoreactivity and oxidative stress are thought to accelerate the pace of aging in DS patients; however, the immunological profile remains elusive. We investigated whether peripheral blood monocyte-derived dendritic cells (MoDCs) in DS patients respond to lipopolysaccharide (LPS) distinctly from non-DS control MoDCs. Eighteen DS patients (age 2–47 years, 12 males) and 22 controls (age 4–40 years, 15 males) were enrolled. CD14-positive monocytes were immunopurified and cultured for 7 days in the presence of granulocyte-macrophage colony-stimulating factor and IL-4, yielding MoDCs in vitro. After the LPS-stimulation for 48 hours from days 7 to 9, culture supernatant cytokines were measured by multiplex cytokine bead assays, and bulk-prepared RNA from the cells was used for transcriptomic analyses. MoDCs from DS patients produced cytokines/chemokines (IL-6, IL-8, TNF-α, MCP-1, and IP-10) at significantly higher levels than those from controls in response to LPS. RNA sequencing revealed that DS-derived MoDCs differentially expressed 137 genes (74 upregulated and 63 downregulated) compared with controls. A gene enrichment analysis identified 5 genes associated with Toll-like receptor signaling (KEGG: hsa04620, P = 0.00731) and oxidative phosphorylation (hsa00190, P = 0.0173) pathways. MoDCs obtained from DS patients showed higher cytokine or chemokine responses to LPS than did control MoDCs. Gene expression profiles suggest that hyperactive Toll-like receptor and mitochondrial oxidative phosphorylation pathways configure the immunoreactive signature of MoDCs in DS patients.

    DOI: 10.1093/cei/uxae048

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  • Survival outcomes of children with relapsed or refractory myeloid leukemia associated with Down syndrome 査読 国際誌

    Raghuram, N; Hasegawa, D; Nakashima, K; Rahman, S; Antoniou, E; Skajaa, T; Merli, P; Verma, A; Rabin, KR; Aftandilian, C; Kotecha, RS; Cheuk, D; Jahnukainen, K; Kolenova, A; Balwierz, W; Norton, A; O'Brien, M; Cellot, S; Chopek, A; Arad-Cohen, N; Goemans, B; Rojas-Vasquez, M; Ariffin, H; Bartram, J; Kolb, EA; Locatelli, F; Klusmann, JH; Hasle, H; Mcguire, B; Hasnain, A; Sung, LL; Hitzler, J

    BLOOD ADVANCES   7 ( 21 )   6532 - 6539   2023年11月   ISSN:2473-9529 eISSN:2473-9537

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    記述言語:英語   出版者・発行元:Blood Advances  

    Children with Down syndrome (DS) are at a significantly higher risk of developing acute myeloid leukemia, also termed myeloid leukemia associated with DS (ML-DS). In contrast to the highly favorable prognosis of primary ML-DS, the limited data that are available for children who relapse or who have refractory ML-DS (r/r ML-DS) suggest a dismal prognosis. There are few clinical trials and no standardized treatment approach for this population. We conducted a retrospective analysis of international study groups and pediatric oncology centers and identified 62 patients who received treatment with curative intent for r/r ML-DS between year 2000 to 2021. Median time from diagnosis to relapse was 6.8 (range, 1.1-45.5) months. Three-year event-free survival (EFS) and overall survival (OS) were 20.9 ± 5.3% and 22.1 ± 5.4%, respectively. Survival was associated with receipt of hematopoietic stem cell transplantation (HSCT) (hazard ratio [HR], 0.28), duration of first complete remission (CR1) (HR, 0.31 for > 12 months) and attainment of remission after relapse (HR, 4.03). Patients who achieved complete remission (CR) before HSCT, had an improved OS and EFS of 56.0 ± 11.8% and 50.5 ± 11.9%, respectively compared to those who underwent HSCT without CR (3-year OS and EFS of 10.0 ± 9.5%). Treatment failure after HSCT was predominantly

    DOI: 10.1182/bloodadvances.2022009381

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  • POT1a deficiency in mesenchymal niches perturbs B-lymphopoiesis 査読 国際誌

    Nakashima, K; Kunisaki, Y; Hosokawa, K; Gotoh, K; Yao, H; Yuta, R; Semba, Y; Nogami, J; Kikushige, Y; Stumpf, PS; MacArthur, BD; Kang, D; Akashi, K; Ohga, S; Arai, F

    COMMUNICATIONS BIOLOGY   6 ( 1 )   996   2023年9月   eISSN:2399-3642

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    担当区分:筆頭著者   記述言語:英語   出版者・発行元:Communications Biology  

    Protection of telomeres 1a (POT1a) is a telomere binding protein. A decrease of POT1a is related to myeloid-skewed haematopoiesis with ageing, suggesting that protection of telomeres is essential to sustain multi-potency. Since mesenchymal stem cells (MSCs) are a constituent of the hematopoietic niche in bone marrow, their dysfunction is associated with haematopoietic failure. However, the importance of telomere protection in MSCs has yet to be elucidated. Here, we show that genetic deletion of POT1a in MSCs leads to intracellular accumulation of fatty acids and excessive ROS and DNA damage, resulting in impaired osteogenic-differentiation. Furthermore, MSC-specific POT1a deficient mice exhibited skeletal retardation due to reduction of IL-7 producing bone lining osteoblasts. Single-cell gene expression profiling of bone marrow from POT1a deficient mice revealed that B-lymphopoiesis was selectively impaired. These results demonstrate that bone marrow microenvironments composed of POT1a deficient MSCs fail to support B-lymphopoiesis, which may underpin age-related myeloid-bias in haematopoiesis.

    DOI: 10.1038/s42003-023-05374-0

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  • Pediatric leukemia and maternal occupational exposure to anticancer drugs: the Japan Environment and Children's Study 査読 国際誌

    Yamamoto, S; Sanefuji, M; Suzuki, M; Sonoda, Y; Hamada, N; Kato, W; Ono, H; Oba, U; Nakashima, K; Ochiai, M; Kusuhara, K; Koga, Y; Ohga, S

    BLOOD   143 ( 4 )   311 - 319   2024年1月   ISSN:0006-4971 eISSN:1528-0020

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    記述言語:英語   出版者・発行元:Blood  

    Occupational exposure to medical agents and ionizing radiation has been suggested as a possible risk factor for childhood cancer. However, the relationship between such exposure and pediatric malignant neoplasms has not yet been comprehensively studied. This cohort study aimed to investigate the association between parental occupational exposure to hazardous medical agents or ionizing radiation and the risk of childhood cancer in offspring. Data from a large birth cohort in Japan, which included 104 062 fetuses, were analyzed. The primary outcome was the development of leukemia or brain tumors diagnosed by community physicians during the first 3 years after birth. Exposure factors were medical agents, including anticancer agents, ionizing radiation, and anesthetics, handled by mothers during pregnancy or by fathers for 3 months before conception. The incidence of leukemia, but not of brain tumors, was higher in mothers exposed to anticancer drugs. Multivariable regression analysis showed that maternal exposure to anticancer drugs was associated with an increased risk of leukemia in offspring older than 1 year (adjusted relative risk, 7.99 [95% confidence interval, 1.98-32.3]). Detailed information obtained from medical certificates of patients with identified leukemia revealed no infant leukemia but acute lymphoblastic leukemias in the exposed group. Our findings suggest that maternal occupational exposure to anticancer drugs may be a potential risk factor for acute lymphoblastic leukemia in offspring older than 1 year. Effective prevention methods may be necessary to prevent maternal exposure to anticancer drugs and to reduce the risk of childhood malignant neoplasms.

    DOI: 10.1182/blood.2023021008

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  • TRK-inhibitor control of an <i>NTRK</i>-rearranged spindle cell tumor with malignant transformation in an adolescent 査読 国際誌

    Higuchi, N; Honda, Y; Koga, Y; Asai, H; Ono, H; Kato, W; Nakashima, K; de la Cuesta, E; Tsujino, T; Yamamoto, H; Kusuhara, K; Hisaoka, M; Ohga, S

    PEDIATRIC BLOOD & CANCER   70 ( 9 )   e30379   2023年9月   ISSN:1545-5009 eISSN:1545-5017

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    記述言語:英語   出版者・発行元:Pediatric Blood and Cancer  

    DOI: 10.1002/pbc.30379

    Web of Science

    Scopus

    PubMed

  • INFANTILE NEUROBLASTOMA AND MATERNAL OCCUPATIONAL EXPOSURE TO MEDICAL AGENTS 査読 国際誌

    Koga, Y; Sanefuji, M; Toya, S; Oba, U; Nakashima, K; Ono, H; Yamamoto, S; Suzuki, M; Kusuhara, K; Ohga, S

    PEDIATRIC BLOOD & CANCER   69   2022年11月   ISSN:1545-5009 eISSN:1545-5017

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  • A PRETERM-ONSET JUVENILE MYELOMONOCYTIC LEUKEMIA-LIKE MYELOPROLIFERATION WITH PTPN11 MUTATION 査読 国際誌

    Yamamoto, S; Nakao, S; Koga, Y; Inoue, H; Nakashima, K; Ishii, K; Semba, Y; Maeda, T; Akashi, K; Ohga, S

    PEDIATRIC BLOOD & CANCER   69   2022年11月   ISSN:1545-5009 eISSN:1545-5017

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▼全件表示

講演・口頭発表等

  • 顆粒球肉腫の3例

    中島 健太郎, 古賀 友紀

    日本小児血液がん学会  2014年11月 

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    記述言語:日本語  

    国名:日本国  

  • BCOR-CCNB3融合遺伝子が検出された未分化肉腫の2例

    中島 健太郎

    第36回日本小児病理研究会学術集会  2016年8月 

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    開催年月日: 2016年8月

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:九州大学   国名:日本国  

    当院で未分化肉腫と診断された4例のうち2例にBCOR-CCNB3が検出された。症例1は7歳女児。6か月時に腰仙部に腫瘤が出現、生検で悪性神経鞘腫が疑われるも確定診断に至らず、未分化肉腫として腫瘍切除術、放射線療法を行うも再発を繰り返し当院紹介。腫瘍亜全摘術、化学療法、放射線療法を行ったが脳転移をきたし永眠した。症例2は12歳女児。左大腿部痛が出現し、CTで骨盤底に腫瘍を認め、生検で未分化肉腫と診断した。化学療法、放射線療法後に自家末梢血幹細胞移植併用超大量化学療法を施行した。腫瘤は残存しているが、治療終了後3年経過し再増大はない。 未分化肉腫は、「あらゆる解析系を用いてもその分化方向が不明であり、既知のいずれの分類にも該当しないもの」と定義され、2013年版の新WHO分類で再編された。近年、軟部肉腫においてBCOR-CCNB3やCIC-DUX4など新たな融合遺伝子が発見され注目されている。BCOR-CCNB3陽性未分化肉腫のまとまった報告は少なく、その臨床像は不明な点も多いが、予後不良な経過を辿る症例もある一方で、集学的治療により治癒率が向上するとの報告もある。当院で経験したBCOR-CCNB3陽性の未分化肉腫の2例のうち、1例は強力な化学療法と放射線治療により腫瘍残存のまま寛解生存しており、積極的かつ強力な集学的治療が奏効する可能性が示唆された。

  • 脳幹部腫瘍に対しベバシズマブにて症状の改善を認めた3例

    中島 健太郎

    小児血液・がん学会  2015年11月 

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    開催年月日: 2015年11月 - 2016年6月

    記述言語:日本語  

    開催地:山梨県甲府   国名:日本国  

    【はじめに】ベバシズマブは血管内皮細胞増殖因子(VEGF)に対する抗モノクローナル抗体で、腫瘍への新生血管の抑制作用により腫瘍の成長を阻害し、また血管平滑筋に作用して膜透過性を改善することにより浮腫を改善させる機序も報告されている。当科の脳幹部腫瘍小児例に対しベバシズマブを使用し、症状の著明改善を認めた3例について報告する。 【症例】症例1は13歳男児。頸部痛を主訴に近医を受診、生検にて延髄膠芽腫(脊髄播種あり)と診断した。テモゾロミド+放射線療法を施行するも麻痺症状等の進行を認めたため、ベバシズマブ投与

MISC

所属学協会

  • 日本小児科学会

  • 日本小児血液がん学会

  • 日本血液学会

学術貢献活動

  • 座長(Chairmanship)

    第486回日本小児科学会福岡地方会例会  ( 福岡大学 ) 2015年10月

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    種別:大会・シンポジウム等 

共同研究・競争的資金等の研究課題

  • 臍帯血有核赤血球の免疫学的応答性と機能的意義の解明

    研究課題/領域番号:26860849  2014年 - 2016年

    科学研究費助成事業  若手研究(B)

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    担当区分:研究代表者  資金種別:科研費

教育活動概要

  • 医学部医学科5、6年生への実習指導(外来実習、まとめにおける指導)

社会貢献・国際連携活動概要

  • 小児がんサバイバーの社会的自立を支援する目的での小児がんキャンプの企画(にこスマ九州)
    こどもホスピスプロジェクトにおける小児がん終末期患者医療体制への協力

社会貢献活動

  • 韓国からの医学生実習受け入れ、指導

    2015年

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    韓国からの医学生実習受け入れ、指導

学内運営に関わる各種委員・役職等

  • 2015年4月 - 2016年3月   その他 九州大学病院小児科病棟副病棟医長