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。

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、委員長、事務局として土屋邦彦講師、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。神経芽腫に対しては、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、家原知子准教授が低リスク神経芽腫に対する臨床試験と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。

腎芽腫に対しては、JWiTS（日本ウィルムス腫瘍研究グループ）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）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キメラ遺伝子解析や、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。

• 横紋筋肉腫研究について
• 神経芽腫研究について
• 悪性ラブドイド腫瘍研究について

• 日本癌学会
• 日本癌治療学会
• 日本小児血液・がん学会
• 日本造血細胞移植学会
• 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

• 日本小児血液・がん専門医研修施設

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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

7. 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.

8. 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.

9. 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

10. 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.

11. 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.

12. 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.

13. 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

14. 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

15. 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.

16. 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.

17. 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.

18. 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.

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

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.