Updated on 2025/06/18

Information

 

写真a

 
NAKASHIMA KENTARO
 
Organization
Kyushu University Hospital Pediatrics Assistant Professor
School of Medicine Department of Medicine(Concurrent)
Title
Assistant Professor
Profile
小児科 教育主任

Degree

  • Ph.D (Kyushu University, Japan)

Education

  • Kyushu University   医学部   医学科

    1999.4 - 2005.3

Research Interests・Research Keywords

  • Research theme: Analysis of immune and hematopoietic abnormalities in Down syndrome

    Keyword: Down syndrome, leukemia, Dendritic cell

    Research period: 2024.4 - 2026.3

Papers

  • Azacitidine treatment for myeloid leukemia associated with Down syndrome: A nationwide retrospective study in Japan Reviewed International journal

    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   2024.10   ISSN:1545-5009 eISSN:1545-5017

     More details

    Language:English   Publisher: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

    Scopus

    PubMed

  • The immunoreactive signature of monocyte-derived dendritic cells from patients with Down syndrome Reviewed International journal

    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   2024.6   ISSN:0009-9104 eISSN:1365-2249

     More details

    Authorship:Lead author   Language:English   Publisher: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

    Web of Science

    Scopus

    PubMed

  • Survival outcomes of children with relapsed or refractory myeloid leukemia associated with Down syndrome Reviewed International journal

    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   2023.11   ISSN:2473-9529 eISSN:2473-9537

     More details

    Language:English   Publisher: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

    Web of Science

    Scopus

    PubMed

  • POT1a deficiency in mesenchymal niches perturbs B-lymphopoiesis Reviewed International journal

    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   2023.9   eISSN:2399-3642

     More details

    Authorship:Lead author   Language:English   Publisher: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

    Web of Science

    Scopus

    PubMed

  • Parental occupational exposure to anticancer drugs and radiation: Risk of fetal loss and physical abnormalities in The Japan Environment and Children's Study

    Yamamoto, S; Sanefuji, M; Inoue, H; Inoue, M; Shimo, Y; Toya, S; Suzuki, M; Abe, N; Hamada, N; Oba, U; Nakashima, K; Ochiai, M; Suga, R; Koga, Y; Tsuji, M; Kato, K; Ohga, S

    EARLY HUMAN DEVELOPMENT   201   106195   2025.2   ISSN:0378-3782 eISSN:1872-6232

     More details

    Language:English   Publisher:Early Human Development  

    Background: Many studies have indicated an association between maternal occupational exposure to hazardous agents, such as anticancer drugs and ionizing radiation, and an increased risk of adverse pregnancy outcomes, including stillbirths or miscarriages and physical abnormalities in offspring. However, the effects of recent advancements in protective measures to reduce these risks have not been clarified. Aim To investigate the current impact of parental occupational exposure to anticancer drugs and ionizing radiation on stillbirths or miscarriages as well as physical abnormalities under the circumstances of the developed safety protocols. Methods: This cohort study utilized The Japan Environment and Children's Study dataset, which included 96,606 fetuses born between January 2011 and March 2014. This study focused on the association between occupational exposure to these agents during pregnancy and the incidence of stillbirths or miscarriages and physical abnormalities in offspring, employing Poisson regression models for adjusted relative risk. Results: From the study population, 471 cases of stillbirths or miscarriages and 4493 infants with physical abnormalities were identified. Fisher's exact tests indicated no significant differences in fetal loss or physical abnormalities between the exposure groups. A multivariable analysis also found no significant association between maternal exposure to anticancer drugs and ionizing radiation and these adverse outcomes. Conclusion: Under improved safety measures, maternal occupational exposure to anticancer drugs and ionizing radiation does not significantly affect the occurrence of stillbirths or miscarriages and physical abnormalities in offspring. These findings highlight the critical role of current safety practices and indicate lower reproductive risks with proper precautions.

    DOI: 10.1016/j.earlhumdev.2025.106195

    Web of Science

    Scopus

    PubMed

  • Infantile neuroblastoma and maternal occupational exposure to medical agents

    Koga Y., Sanefuji M., Toya S., Oba U., Nakashima K., Ono H., Yamamoto S., Suzuki M., Sonoda Y., Ogawa M., Yamamoto H., Kusuhara K., Ohga S., Katoh T., Suganuma N., Kurozawa Y., Shima M., Iso H., Nakayama T., Inadera H., Yamagata Z., Ito S., Mori C., Hashimoto K., Yaegashi N., Kishi R., Ohya Y., Yamazaki S., Kamijima M.

    Pediatric Research   97 ( 1 )   365 - 369   2025.1   ISSN:00313998

     More details

    Language:English   Publisher:Pediatric Research  

    Background: Healthcare workers are often exposed to hazardous agents and are at risk for adverse health consequences that affect not only themselves but also their infants. This study aimed to examine whether such occupational exposure increased the risk of childhood cancer in offspring. Methods: We used the dataset of the Japan Environment and Children’s Study, a nationwide birth cohort involving over 100,000 mother–child pairs. Information was obtained via successive questionnaires that were completed until the child turned 1 year of age. The parents were asked whether they occupationally handled medical agents during pregnancy. Results: A total of 26 infants developed neoplasms: neuroblastoma, leukemia, and brain tumor. The incidence of neuroblastoma was significantly higher in infants whose mothers were exposed to radiation (3/2142: 140.1 per 100,000 population) than in those who were not (12/90,384: 13.3 per 100,000 population). Multivariable regression analyses revealed a close association between maternal irradiation and the development of neuroblastoma (adjusted incident rate ratio: 10.68 [95% confidence interval: 2.98‒38.27]). Conclusions: The present study demonstrated, for the first time, a potential association between maternal occupational exposure and the occurrence of neuroblastoma in offspring. Further studies involving the large pediatric cancer registries are needed to confirm these preliminary results. Impact: Healthcare workers are often exposed to hazardous agents and are at risk for adverse health consequences that affect not only themselves but also their infants. This study examined the association between such occupational exposure and offspring’s cancers that developed until the age of 1 year. Maternal exposure to ionizing radiation was associated with infantile neuroblastoma in offspring. Further studies involving the large pediatric cancer registries are needed to confirm these preliminary results.

    DOI: 10.1038/s41390-021-01634-z

    Scopus

    PubMed

  • Pediatric leukemia and maternal occupational exposure to anticancer drugs: the Japan Environment and Children's Study Reviewed International journal

    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   2024.1   ISSN:0006-4971 eISSN:1528-0020

     More details

    Language:English   Publisher: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

    Web of Science

    Scopus

    PubMed

  • TRK-inhibitor control of an <i>NTRK</i>-rearranged spindle cell tumor with malignant transformation in an adolescent Reviewed International journal

    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   2023.9   ISSN:1545-5009 eISSN:1545-5017

     More details

    Language:English   Publisher:Pediatric Blood and Cancer  

    DOI: 10.1002/pbc.30379

    Web of Science

    Scopus

    PubMed

  • INFANTILE NEUROBLASTOMA AND MATERNAL OCCUPATIONAL EXPOSURE TO MEDICAL AGENTS Reviewed International journal

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

    PEDIATRIC BLOOD & CANCER   69   2022.11   ISSN:1545-5009 eISSN:1545-5017

     More details

  • A PRETERM-ONSET JUVENILE MYELOMONOCYTIC LEUKEMIA-LIKE MYELOPROLIFERATION WITH PTPN11 MUTATION Reviewed International journal

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

    PEDIATRIC BLOOD & CANCER   69   2022.11   ISSN:1545-5009 eISSN:1545-5017

     More details

▼display all

Presentations

▼display all

MISC

Professional Memberships

  • 日本小児科学会

  • 日本小児血液がん学会

  • 日本血液学会

Academic Activities

  • 座長(Chairmanship)

    第486回日本小児科学会福岡地方会例会  ( Japan ) 2015.10

     More details

    Type:Competition, symposium, etc. 

Research Projects

  • 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

    Grant number:26860849  2014 - 2016

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

      More details

    Authorship:Principal investigator  Grant type:Scientific research funding

Educational Activities

  • 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)

Outline of Social Contribution and International Cooperation activities

  • 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

Social Activities

  • 韓国からの医学生実習受け入れ、指導

    2015

     More details

    韓国からの医学生実習受け入れ、指導