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小児に発生する固形腫瘍について、基礎研究から臨床研究まで幅広く研究を行っています。また、基礎研究で得られた知見を臨床に生かせるように、当研究室の研究成果を、全国的な臨床試験に組み込んでその有用性を検討しています。

臨床研究

神経芽腫において、JNBSG（日本神経芽腫研究グループ、現JCCG神経芽腫委員会）のメンバーとして臨床試験に積極的に関わっています。JNBSG臨床試験では、家原知子教授が中間リスク神経芽腫に対する臨床試験の主任研究者を務めています。さらに、再発神経芽腫に対する抗GD2抗体とイリノテカン、テモゾロミド併用の有効性を検証する医師主導治験の治験調整医師を務めています。また、柳生茂希講師が、低・中間リスク群の新しい観察研究の主任研究者を務めています。

横紋筋肉腫については、細井 創名誉教授がJRSG（日本横紋筋肉腫研究グループ）の立ち上げに当初より関わり、リスク群層別化治療システムの導入や、遺伝子診断を含む中央病理診断システムの構築の中心として、日本最初の本格的な全国的小児がん臨床試験の開始に多大な貢献をしてきました。現在、JRSGの後継となる日本小児がん研究グループJCCGの横紋筋肉腫委員会では、主任研究医師として土屋邦彦准教授、宮地　充講師が携わり、低リスク群には晩期障害を軽減し、治療成績の不良な高リスク群には新たな治療による成績の改善を目指しています。

腎芽腫に対しては、JWiTS（日本ウィルムス腫瘍研究グループ、現JCCG腎腫瘍委員会）と共同で、小児がん患者の腎機能障害について研究を行っております。また、肝芽腫についてはJPLT（日本小児肝癌スタディグループ、現JCCG肝腫瘍委員会）の臨床研究に参加しております。

小児固形腫瘍にしばしば認められる融合遺伝子解析や、骨髄中、末梢血幹細胞液中に混入する微量の腫瘍細胞の検出、神経芽腫患者の血清中MYCN遺伝子解析によるMYCN遺伝子増幅診断や治療効果判定、横紋筋肉腫患者の血清中micro RNA解析による診断など、当科で開発した研究結果による小児がんの診断を積極的に行っており、診断や治療方針に迷われる症例について、全国の施設から多数の依頼を受け、診断に役立てていただいております。

基礎研究

研究メンバー

教授 家原 知子
名誉教授・特任教授 細井 創
准教授 土屋 邦彦
講師 柳生 茂希
講師 宮地 充
学内講師 吉田 秀樹
助教 富田 晃正
助教 末松 正也
助教 大矢 暁
助教 杉立 有弥
特任講師 菊地 顕
特任講師 勝見 良樹
大学院生 生嶋 諒
大学院生 池村 高明
大学院生 内藤 優樹
大学院生 喜多 優介
大学院生 馬奈木 彰弘

関係学会

  • 日本癌学会
  • 日本癌治療学会
  • 日本小児血液・がん学会
  • 日本造血・免疫細胞療法学会
  • 日本がん検診・診断学会
  • 米国癌学会（American Association for Cancer Research）
  • 米国臨床腫瘍学会（American Society of Clinical Oncology）など

学会認定施設

  • 日本小児血液・がん専門医研修施設

業績

  1. Kondo H, Kikuchi K, Tomida A, Yoshida H, Miyachi M, Katsumi Y, Yagyu S, Tsuchiya K, Iehara T. Identifying miRNAs as predictive markers of good prognosis in neuroblastoma. Pediatr Int. 2025 Jan-Dec;67(1):e70154. doi: 10.1111/ped.70154. PMID: 40613527.

  2. Oya S, Yoshida H, Tomida A, Miyachi M, Yagyu S, Katsumi Y, Kikuchi K, Tsuchiya K, Konishi E, Subramanian S, Yamamoto M, Iehara T. A novel conditionally replicative oncolytic adenovirus under the control of the SALL4 promoter inhibits the growth of rhabdoid tumors. Mol Cancer Ther. 2025 May 19. doi: 10.1158/1535-7163.MCT-24-0710. Epub ahead of print. PMID: 40386952.

  3. Miyachi M, Sugimoto Y, Sugitatsu Y, Tomida A, Yoshida H, Tsuchiya K, Umebayashi D, Yamanaka T, Hashimoto N, Shishido-Hara Y, Konishi E, Iehara T. Entrectinib treatment induces a durable response against ARHGEF11::NTRK1 fusion gene-positive spinal cord diffuse pediatric-type high-grade glioma. Pediatr Blood Cancer. 2023 Oct;70(10):e30513. doi: 10.1002/pbc.30513. Epub 2023 Jul 1. PMID: 37393426.

  4. Shoji C, Kikuchi K, Yoshida H, Miyachi M, Yagyu S, Tsuchiya K, Nakaya T, Hosoi H, Iehara T. In ovo chorioallantoic membrane assay as a xenograft model for pediatric rhabdomyosarcoma. Oncol Rep. 2023 Apr;49(4):76. doi: 10.3892/or.2023.8513. Epub 2023 Mar 3. PMID: 36866753; PMCID: PMC10018452.

  5. Kaneda D, Iehara T, Kikuchi K, Sugimoto Y, Nakagawa N, Yagyu S, Miyachi M, Konishi E, Sakai T, Hosoi H. The histone deacetylase inhibitor OBP-801 has in vitro/in vivo anti-neuroblastoma activity. Pediatr Int. 2022 Jan;64(1):e15159. doi: 10.1111/ped.15159. PMID: 35727889.

  6. Tomida A, Chiyonobu T, Tokuda S, Miyachi M, Murashima K, Hirata M, Nakagawa M, Iehara T, Kuroda J, Takayama K. Pleomorphic rhabdomyosarcoma in a young adult harboring a novel germline MSH2 variant. Hum Genome Var. 2022 Mar 8;9(1):8. doi: 10.1038/s41439-022-00185-x. PMID: 35260566; PMCID: PMC8904467.

  7. Suematsu M, Yagyu S, Hosoi H, Iehara T. Infantile mediastinal neuroblastoma presenting as an oncologic emergency: usefulness of serum-based MYCN gene amplification analysis for risk stratification. BMJ Case Rep. 2021 Dec 31;14(12):e246889. doi: 10.1136/bcr-2021-246889. PMID: 34972781; PMCID: PMC8720954.

  8. Katsumi Y, Iehara T, Kuwahara Y, Tsuchiya K, Konishi E, Hosoi H. Diverse outcomes in extra-cranial rhabdoid tumors: A single institute experience. Pediatr Hematol Oncol. 2022 Apr;39(3):278-285. doi: 10.1080/08880018.2021.1986614. Epub 2021 Oct 20. PMID: 34668815.

  9. Kanayama T, Miyachi M, Sugimoto Y, Yagyu S, Kikuchi K, Tsuchiya K, Iehara T, Hosoi H. Reduced B7-H3 expression by PAX3-FOXO1 knockdown inhibits cellular motility and promotes myogenic differentiation in alveolar rhabdomyosarcoma. Sci Rep. 2021 Sep 22;11(1):18802. doi: 10.1038/s41598-021-98322-z. PMID: 34552155; PMCID: PMC8458399.

  10. Miyagaki S, Kikuchi K, Mori J, Lopaschuk GD, Iehara T, Hosoi H. Inhibition of lipid metabolism exerts antitumor effects on rhabdomyosarcoma. Cancer Med. 2021 Sep;10(18):6442-6455. doi: 10.1002/cam4.4185. Epub 2021 Sep 2. PMID: 34472721; PMCID: PMC8446407.

  11. Tomida A, Yagyu S, Nakamura K, Kubo H, Yamashima K, Nakazawa Y, Hosoi H, Iehara T. Inhibition of MEK pathway enhances the antitumor efficacy of chimeric antigen receptor T cells against neuroblastoma. Cancer Sci. 2021 Oct;112(10):4026-4036. doi: 10.1111/cas.15074. Epub 2021 Aug 24. PMID: 34382720; PMCID: PMC8486218.

  12. Kubo H, Yagyu S, Nakamura K, Yamashima K, Tomida A, Kikuchi K, Iehara T, Nakazawa Y, Hosoi H. Development of non-viral, Ligand-dependent, EPHB4-specific chimerc antigen receptor T cells for treatment of rhabdomyosarcoma. Molecular Therapy Oncolytics. 20:646-658, 2021.

  13. Sugimoto Y, Katsumi Y, Iehara T, Kaneda D, Tomoyasu C, Ouchi K, Yoshida H, Miyachi M, Yagyu S, Kikuchi K, Tsuchiya K, Kuwahara Y, Sakai T, Hosoi H. The novel histone deacetylase inhibitor OBP-801 induces apoptosis in rhabdoid tumors by releasing the silencing of NOXA. Mol Cancer Ther. 2020 Aug 26:molcanther.0243.2020. doi: 10.1158/1535-7163.

  14. Iehara T, Manabe A, Hosoi H. Statement on the prevention and treatment of COVID-19 in patients with pediatric cancer in Japan. Pediatr Blood Cancer. 2020 Jun 22:e28440. doi: 10.1002/pbc.28440.

  15. Ouchi K, Miyachi M, Yagyu S, Kikuchi K, Kuwahara Y, Tsuchiya K, Iehara T, Hosoi H. Oncogenic role of HMGA2 in fusion-negative rhabdomyosarcoma cells.Cancer Cell Int. 2020 May 24;20:192. doi: 10.1186/s12935-020-01282-z.

  16. Iehara T, Yoneda A, Kikuta A, Muraji T, Tokiwa K, Takahashi H, Teramukai S, Takimoto T, Yagyu S, Hosoi H, Tajiri T; Japan Children’s Cancer Group Neuroblastoma Committee. A phase II JN-I-10 efficacy study of IDRF-based surgical decisions and stepwise treatment intensification for patients with intermediate-risk neuroblastoma: a study protocol. BMC Pediatr. 2020 May 12;20(1):212. doi: 10.1186/s12887-020-02061-5.

  17. Hiramaoto R, Miyachi M, Nitta Y, Yoshida H, Kuwahara Y, Tsuchiya K, Iehara T, Yarita K, Kamei K, Hosoi H. Detection of circulating fungal DNA by polymerase chain reaction in a fatal case of Cunninghamella bertholletiae infection. IDCases Volume 20, 2020, e00760

  18. Iehara T, Yoneda A, Yokota I, Takahashi H, Teramukai S, Kamijyo T, Nakazawa A, Takimoto T, Kikuta A, Yagyu S, Ikeda H, Nakagawara A, Tajiri T; Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG). Results of a prospective clinical trial JN-L-10 using image-defined risk factors to inform surgical decisions for children with low-risk neuroblastoma disease: A report from the Japan Children's Cancer Group Neuroblastoma Committee. Pediatr Blood Cancer. 2019 Jul 24:e27914. doi: 10.1002/pbc.27914.

  19. Iehara T, Yagyu S, Gotoh T, Ouchi K, Yoshida H, Miyachi M, Kikuchi K, Sugimoto T, Hosoi H. A prospective evaluation of liquid biopsy for detecting MYCN amplification in neuroblastoma patients. Jpn J Clin Oncol. 49(8): 743-748, 2019.

  20. Sugimoto T, Kuroda H, Yagyu S, Gotoh T, Osone S, Tamura S, Iehara T, Hosoi H. Cellular and molecular characteristics of established neuroblastoma cell lines. Journal of Cnacer Research and Therapeutic Oncology 7:1-15.2019

  21. Tomoyasu C, Kikuchi K, Kaneda D, Yagyu S, Miyachi M, Tsuchiya K, Iehara T,Sakai T, Hosoi H. OBP‑801, a novel histone deacetylase inhibitor, induces M‑phase arrest and apoptosis in rhabdomyosarcoma cells. Oncol Rep. 41(4):2601. 2019Otabe O, Kikuchi K, Tsuchiya K, Katsumi Y, Yagyu S, Miyachi M, Iehara T, Hosoi H. MET/ERK2 pathway regulates the motility of human alveolar rhabdomyosarcoma cells. Oncol Rep. 2017; 37: 98-104.

  22. Nitta Y, Miyachi M, Tomida A, Sugimoto Y, Nakagawa N, Yoshida H, Ouchi K,Tsuchiya K, Iehara T, Konishi E, Umeda K, Okamoto T, Hosoi H. Identification of a novel BOC-PLAG1 fusion gene in a case of lipoblastoma. Biochem Biophys Res Commun.;512(1):49-52. 2019.

  23. Nakagawa N, Kikuchi K, Yagyu S, Miyachi M, Iehara T, Tajiri T, Sakai T, Hosoi H. Mutations in the RAS pathway as potential precision medicine targets in treatment of rhabdomyosarcoma. Biochem Biophys Res Commun.;512(3):524-530. 2019.

  24. Otabe O, Kikuchi K, Tsuchiya K, Katsumi Y, Yagyu S, Miyachi M, Iehara T, Hosoi H. MET/ERK2 pathway regulates the motility of human alveolar rhabdomyosarcoma cells. Oncol Rep. 2017 Jan;37(1):98-104

  25. Iehara T, Yagyu S, Tsuchiya K, Kuwahara Y, Miyachi M, Tajiri T, Sugimoto T, Sawada T, Hosoi H. Residual tumor in cases of intermediate-risk neuroblastoma did not influence the prognosis. Jpn J Clin Oncol. Jul;46(7):661-6. 2016

  26. Tsuma Y, Miyachi M, Ouchi K, Tsuchiya K, Iehara T, Naitoh Y, Konishi E,Yanagisawa A, Hosoi H. Neoadjuvant Treatment With Cyclooxygenase-2 Inhibitor and Prednisolone Allows Conservative Surgery for Inflammatory Myofibroblastic Tumor of the Bladder. J Pediatr Hematol Oncol. 2016 Jun 17.

  27. Yagyu S, Iehara T, Tanaka S, Gotoh T, Misawa-Furihata A, Sugimoto T, London WB, Hogarty MD, Teramukai S, Nakagawara A, Hiyama E, Maris JM, Hosoi H. Serum-Based Quantification of MYCN Gene Amplification in Young Patients with Neuroblastoma: Potential Utility as a Surrogate Biomarker for Neuroblastoma. PLoS One. 2016 Aug 11;11(8):e0161039. doi: 10.1371/journal.pone.0161039.

  28. Iehara T, Yagyu S, Tsuchiya K, Kuwahara Y, Miyachi M, Tajiri T, Sugimoto T, Sawada T, Hosoi H. Residual tumor in cases of intermediate-risk neuroblastoma did not influence the prognosis. Jpn J Clin Oncol. 2016; 46: 661-6.

  29. Ouchi K, Kuwahara Y, Iehara T, Miyachi M, Katsumi Y, Tsuchiya K, Konishi E, Yanagisawa A, Hosoi H. A NOXA/MCL-1 Imbalance Underlies Chemoresistance of Malignant Rhabdoid Tumor Cells. J Cell Physiol. 2016; 231: 1932-40.

  30. Hosoi H. Current status of treatment for pediatric rhabdomyosarcoma in the USA and Japan. Pediatr Int. 2016; 58: 81-7.

  31. Yoshida H, Miyachi M, Sakamoto K, Ouchi K, Yagyu S, Kikuchi K, Kuwahara Y, Tsuchiya K, Imamura T, Iehara T, Kakazu N, Hojo H, Hosoi H. PAX3-NCOA2 fusion gene has a dual role in promoting the proliferation and inhibiting the myogenic differentiation of rhabdomyosarcoma cells. Oncogene. 2014; 33: 5601-8.

  32. Iehara T, Hamazaki M, Tajiri T, Kawano Y, Kaneko M, Ikeda H, Hosoi H, Sugimoto T, Sawada T; Japanese Infantile Neuroblastoma Cooperative Study Group. Successful treatment of infants with localized neuroblastoma based on their MYCN status. Int J Clin Oncol. 2013; 18: 389-95.

  33. Iehara T, Hiyama E, Tajiri T, Yoneda A, Hamazaki M, Fukuzawa M, Hosoi H, Sugimoto T, Sawada T. Is the prognosis of stage 4s neuroblastoma in patients 12 months of age and older really excellent? Eur J Cancer. 2012; 48: 1707-12.

  34. Katsumi Y, Iehara T, Miyachi M, Yagyu S, Tsubai-Shimizu S, Kikuchi K, Tamura S, Kuwahara Y, Tsuchiya K, Kuroda H, Sugimoto T, Houghton PJ, Hosoi H. Sensitivity of malignant rhabdoid tumor cell lines to PD 0332991 is inversely correlated with p16 expression. Biochem Biophys Res Commun. 2011; 413: 62-8.

  35. Yagyu S, Iehara T, Gotoh T, Miyachi M, Katsumi Y, Kikuchi K, Tsuchiya K, Osone S, Kuroda H, Sugimoto T, Sawada T, Hosoi H. Preoperative analysis of 11q loss using circulating tumor-released DNA in serum: a novel diagnostic tool for therapy stratification of neuroblastoma. Cancer Lett. 2011; 309: 185-9.

  36. Miyachi M, Tsuchiya K, Yoshida H, Yagyu S, Kikuchi K, Misawa A, Iehara T, Hosoi H. Circulating muscle-specific microRNA, miR-206, as a potential diagnostic marker for rhabdomyosarcoma. Biochem Biophys Res Commun. 2010; 400: 89-93.