Faculty Profiles - NAKADA Eiji

Papers - NAKADA Eiji

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多職種から見た骨・軟部腫瘍治療の現状と課題肉腫発生ハイリスク患者に対する遺伝性骨・軟部腫瘍外来の取り組み

二川摩周, 中田英二, 山本英喜, 深野智華, 加藤芙美乃, 大住理沙, 藤原智洋, 国定俊之, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1579 - S1579 2024.6

中田英二, 二川摩周, 平沢晃, 山本英喜, 国定俊之, 板野拓人, 藤原智洋, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1614 - S1614 2024.6

Clinical Application of Unidirectional Porous Hydroxyapatite to Bone Tumor Surgery and Other Orthopedic Surgery. International journal

Toshiyuki Kunisada, Eiji Nakata, Tomohiro Fujiwara, Toshiaki Hata, Kohei Sato, Haruyoshi Katayama, Ayana Kondo, Toshifumi Ozaki

Biomimetics (Basel, Switzerland) 9 ( 5 ) 2024.5

Language：English Publishing type：Research paper (scientific journal)

Unidirectional porous hydroxyapatite (UDPHAp) was developed as a remarkable scaffold characterized by a distinct structure with unidirectional pores oriented in the horizontal direction and connected through interposes. We evaluated the radiographic changes, clinical outcomes, and complications following UDPHAp implantation for the treatment of bone tumors. Excellent bone formation within and around the implant was observed in all patients treated with intralesional resection and UDPHAp implantation for benign bone tumors. The absorption of UDPHAp and remodeling of the bone marrow space was observed in 45% of the patients at a mean of 17 months postoperatively and was significantly more common in younger patients. Preoperative cortical thinning was completely regenerated in 84% of patients at a mean of 10 months postoperatively. No complications related to the implanted UDPHAp were observed. In a pediatric patient with bone sarcoma, when the defect after fibular resection was filled with UDPHAp implants, radiography showed complete resorption of the implant and clear formation of cortex and marrow in the resected part of the fibula. The patient could walk well without crutches and participate in sports activities. UDPHAp is a useful bone graft substitute for the treatment of benign bone tumors, and the use of this material has a low complication rate. We also review and discuss the potential of UDPHAp as a bone graft substitute in the clinical setting of orthopedic surgery.

DOI： 10.3390/biomimetics9050294

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PRRX1-TOP2A interaction is a malignancy-promoting factor in human malignant peripheral nerve sheath tumours. International journal

Shota Takihira, Daisuke Yamada, Tatsunori Osone, Tomoka Takao, Masakiyo Sakaguchi, Michiyuki Hakozaki, Takuto Itano, Eiji Nakata, Tomohiro Fujiwara, Toshiyuki Kunisada, Toshifumi Ozaki, Takeshi Takarada

British journal of cancer 2024.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Paired related-homeobox 1 (PRRX1) is a transcription factor in the regulation of developmental morphogenetic processes. There is growing evidence that PRRX1 is highly expressed in certain cancers and is critically involved in human survival prognosis. However, the molecular mechanism of PRRX1 in cancer malignancy remains to be elucidated. METHODS: PRRX1 expression in human Malignant peripheral nerve sheath tumours (MPNSTs) samples was detected immunohistochemically to evaluate survival prognosis. MPNST models with PRRX1 gene knockdown or overexpression were constructed in vitro and the phenotype of MPNST cells was evaluated. Bioinformatics analysis combined with co-immunoprecipitation, mass spectrometry, RNA-seq and structural prediction were used to identify proteins interacting with PRRX1. RESULTS: High expression of PRRX1 was associated with a poor prognosis for MPNST. PRRX1 knockdown suppressed the tumorigenic potential. PRRX1 overexpressed in MPNSTs directly interacts with topoisomerase 2 A (TOP2A) to cooperatively promote epithelial-mesenchymal transition and increase expression of tumour malignancy-related gene sets including mTORC1, KRAS and SRC signalling pathways. Etoposide, a TOP2A inhibitor used in the treatment of MPNST, may exhibit one of its anticancer effects by inhibiting the PRRX1-TOP2A interaction. CONCLUSION: Targeting the PRRX1-TOP2A interaction in malignant tumours with high PRRX1 expression might provide a novel tumour-selective therapeutic strategy.

DOI： 10.1038/s41416-024-02632-8

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Role of catecholamine synthases in the maintenance of cancer stem-like cells in malignant peripheral nerve sheath tumors. International journal

Haruyoshi Katayama, Atsushi Fujimura, Rongsheng Huang, Yusuke Otani, Takuto Itano, Tomohiro Fujiwara, Toshiyuki Kunisada, Eiji Nakata, Toshifumi Ozaki

Cancer science 115 ( 3 ) 871 - 882 2024.3

Language：English Publishing type：Research paper (scientific journal)

Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that are derived from Schwann cell lineage around peripheral nerves. As in many other cancer types, cancer stem cells (CSCs) have been identified in MPNSTs, and they are considered the cause of treatment resistance, recurrence, and metastasis. As an element defining the cancer stemness of MPNSTs, we previously reported a molecular mechanism by which exogenous adrenaline activates a core cancer stemness factor, YAP/TAZ, through β2 adrenoceptor (ADRB2). In this study, we found that MPNST cells express catecholamine synthases and that these enzymes are essential for maintaining cancer stemness, such as the ability to self-renew and maintain an undifferentiated state. Through gene knockdown and inhibition of these enzymes, we confirmed that catecholamines are indeed synthesized in MPNST cells. The results confirmed that catecholamine synthase knockdown in MPNST cells reduces the activity of YAP/TAZ. These data suggest that a mechanism of YAP/TAZ activation by de novo synthesized adrenaline, as well as exogenous adrenaline, may exist in the maintenance of cancer stemness of MPNST cells. This mechanism not only helps to understand the pathology of MPNST, but could also contribute to the development of therapeutic strategies for MPNST.

DOI： 10.1111/cas.16077

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悪性末梢神経鞘腫瘍において転写因子PRRX1はTOP2Aと相互作用し悪性化を促進させる

たき平将太, 中田英二, 板野拓人, 藤原智洋, 国定俊之, 大曽根達則, 山田大祐, 高尾知佳, 宝田剛志, 尾崎敏文

日本整形外科学会雑誌 98 ( 2 ) S76 - S76 2024.3

肉腫におけるがん遺伝子パネルによるfusion gene同定の意義

中田英二, 藤原智洋, 板野拓人, 片山晴喜, 二川摩周, 山元英崇, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 98 ( 3 ) S1246 - S1246 2024.3

AIとDXを用いた骨・軟部腫瘍診療への新たな挑戦

長谷井嬢, 中原龍一, 藤原智洋, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 98 ( 3 ) S1371 - S1371 2024.3

術前がん患者の各ロコモ度テストにおける関連因子

堅山佳美, 中田英二, 近藤彩奈, 濱田全紀, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 98 ( 3 ) S1321 - S1321 2024.3

悪性末梢神経鞘腫瘍において転写因子PRRX1はTOP2Aと相互作用し悪性化を促進させる

たき平将太, 中田英二, 板野拓人, 藤原智洋, 国定俊之, 大曽根達則, 山田大祐, 高尾知佳, 宝田剛志, 尾崎敏文

日本整形外科学会雑誌 98 ( 2 ) S76 - S76 2024.3

神経線維腫症1型患者由来ヒトiPS細胞株の樹立

大澤太郎, 中田英二, 岡本真幸, 山田大祐, 二川摩周, 高尾知佳, 平沢晃, 尾崎敏文, 宝田剛志

日本レックリングハウゼン病学会学術大会プログラム・抄録集 15回 24 - 24 2024.2

遺伝性骨・軟部腫瘍外来における肉腫発生at-risk者への取り組み

二川摩周, 中田英二, 山本英喜, 深野智華, 加藤芙美乃, 大住理沙, 藤原智洋, 国定俊之, 平沢晃, 尾崎敏文

日本レックリングハウゼン病学会学術大会プログラム・抄録集 15回 25 - 25 2024.2

神経線維腫症1型患者由来ヒトiPS細胞株の樹立

大澤太郎, 中田英二, 岡本真幸, 山田大祐, 二川摩周, 高尾知佳, 平沢晃, 尾崎敏文, 宝田剛志

日本レックリングハウゼン病学会学術大会プログラム・抄録集 15回 24 - 24 2024.2

Changes in Spinal Instability After Conventional Radiotherapy for Painful Vertebral Bone Metastases

Eiji Nakata, Shinsuke Sugihara, Ryuichi Nakahara, Haruyoshi Katayama, Takuto Itano, Toshifumi Ozaki

Cancer Control 31 2024.1

Publishing type：Research paper (scientific journal) Publisher：SAGE Publications

Objective: Precise assessment of spinal instability is critical before and after radiotherapy (RT) for evaluating the effectiveness of RT. Therefore, we retrospectively evaluated the efficacy of RT in spinal instability over a period of 6 months after RT, utilizing the spinal instability neoplastic score (SINS) in patients with painful spinal metastasis. We retrospectively evaluated 108 patients who received RT for painful vertebral metastasis in our institution. Mechanical pain at metastatic vertebrae, radiological responses of irradiated vertebrae, and spinal instability were assessed. Follow-up assessments were done at the start of and at intervals of 1, 2, 3, 4, and 6 months after RT, with the pain disappearing in 67%, 85%, 93%, 97%, and 100% of the patients, respectively. The median SINS were 8, 6, 6, 5, 5, and 4 at the beginning and after 1, 2, 3, 4, and 6 months of RT, respectively. Multivariate analysis revealed that posterolateral involvement of spinal elements (PLISE) was the only risk factor for continuous potentially unstable/unstable spine at 1 month. In conclusion, there was improvement of pain, and recalcification results in regaining spinal stability over time after RT although vertebral body collapse and malalignment occur in some irradiated vertebrae. Clinicians should pay attention to PLISE in predicting continuous potentially unstable/unstable spine.

DOI： 10.1177/10732748241250219

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Other Link： https://journals.sagepub.com/doi/full-xml/10.1177/10732748241250219

Comparison between Cases of Total Hip Arthroplasty Followed by Colonna Capsular Arthroplasty and Lorenz Cast Reduction in Patients with Developmental Dysplasia of the Hip.

Hirosuke Endo, Kazuki Yamada, Tomonori Tetsunaga, Yoshifumi Namba, Yoshihisa Sugimoto, Shigeru Mitani, Eiji Nakata, Toshifumi Ozaki

Acta medica Okayama 77 ( 6 ) 655 - 663 2023.12

Language：English Publishing type：Research paper (scientific journal)

Most patients with developmental dysplasia of the hip (DDH) now receive closed-reduction treatment within 6 months after birth. The long-term outcomes of patients with late-detection DDH have remained unclear. We reviewed the clinical records of 18 patients who underwent Colonna capsular arthroplasty (n=8) or closed reduction (n=10) for developmental dysplasia of the hip as infants or young children and underwent total hip arthroplasty approximately in midlife. Both the Colonna capsular arthroplasty and closed reduction groups achieved good clinical results after total hip arthroplasty. However, the operating time was longer and the improvements of hip range of motion and clinical score were significantly worse in the Colonna capsular arthroplasty group than in the closed reduction group.

DOI： 10.18926/AMO/66159

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【がん時代の整形外科必携! 骨転移診療アップデート】骨転移治療総論骨転移におけるロコモティブシンドローム

中田英二, 堅山佳美, 明崎禎輝, 濱田全紀, 藤原智洋, 国定俊之, 尾崎敏文

臨床整形外科 58 ( 12 ) 1431 - 1438 2023.12

Language：Japanese Publisher：(株)医学書院

＜文献概要＞がんは高齢者に多いため,ロコモティブシンドロームが発生しやすい.がんの切除を行う患者の約9割は,ロコモを合併している.したがって,がん患者では,適切ながんロコモのスクリーニングが重要である.また,最近,がん治療は外来に移行しつつあり,がん患者が日常生活動作を維持することが求められ,がんロコモ予防に対する社会のニーズが増えている.したがって,各施設において,診療科横断的にがんロコモ予防に取り組む体制を構築することが重要である.

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01554&link_issn=&doc_id=20231129020009&doc_link_id=10.11477%2Fmf.1408202843&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1408202843&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

ヒトiPS細胞由来肢芽間葉系細胞から作製した軟骨組織体を用いた骨再生

中田英二, 佐藤浩平, 高尾知佳, 藤澤祐樹, 山田大祐, 上原健敬, 藤原智洋, 尾崎敏文, 宝田剛志

移植 58 ( 3 ) 293 - 293 2023.12

Factors associated with survival in patients with clear cell sarcoma. International journal

Tomohiro Fujiwara, Toshiyuki Kunisada, Eiji Nakata, Toshiharu Mitsuhashi, Toshifumi Ozaki, Akira Kawai

The bone & joint journal 105-B ( 11 ) 1216 - 1225 2023.11

Language：English Publishing type：Research paper (scientific journal)

AIMS: Clear cell sarcoma (CCS) of soft-tissue is a rare melanocytic subtype of mesenchymal malignancy. The aim of this study was to investigate the clinical and therapeutic factors associated with increased survival, stratified by clinical stage, in order to determine the optimal treatment. METHODS: The study was a retrospective analysis involving 117 patients with histologically confirmed CCS, between July 2016 and November 2017, who were enrolled in the Bone and Soft Tissue Tumour Registry in Japan. RESULTS: The five- and ten-year survival rates were 41% (95% confidence interval (CI) 29 to 52) and 37% (95% CI 25 to 49), respectively. On multivariable analysis, the size of the tumour of > 10 cm (p = 0.006), lymph node metastasis at the time of diagnosis (p < 0.001), distant metastases at the time of diagnosis (p < 0.001), and no surgery for the primary tumour (p = 0.019) were independently associated with a poor survival. For N0M0 CCS (n = 68), the development of distant metastases was an independent prognostic factor for survival (early (< 12 months), hazard ratio (HR) 116.78 (95% CI 11.69 to 1,166.50); p < 0.001; late (> 12 months), HR 14.79 (95% CI 1.66 to 131.63); p = 0.016); neoadjuvant/adjuvant chemotherapy (p = 0.895) and/or radiotherapy (p = 0.216) were not significantly associated with survival. The five-year cumulative incidence of local recurrence was 19% (95% CI 8 to 35) and the size of the tumour was significantly associated with an increased rate of local recurrence (p = 0.012). For N1M0 CCS (n = 18), the risk of mortality was significantly lower in patients who underwent surgery for both the primary tumour and lymph node metastases (HR 0.03 (95% CI 0.00 to 0.56); p = 0.020). For M1 CCS (n = 31), excision of the primary tumour was independently associated with better survival (HR 0.26 (95% CI 0.09 to 0.76); p = 0.013). There was no significant difference in survival between the different types of systemic treatment (p = 0.523). CONCLUSION: Complete excision of the primary tumour and lymph nodes is associated with a better survival in patients with CCS. Systemic treatment appears to provide limited benefits, demonstrating a pressing need for novel systemic agents.

DOI： 10.1302/0301-620X.105B11.BJJ-2022-0743.R3

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神経線維腫症1型による叢状神経線維腫に対するセルメチニブの有効性

中田英二, 藤原智洋, 国定俊之, 二川摩周, 山本英喜, 十川麗美, 加藤芙美乃, 片山晴喜, 板野拓人, 近藤彩奈, 平沢晃, 尾崎敏文

中国・四国整形外科学会雑誌 35 ( 3 ) 428 - 428 2023.11

著明な疼痛を伴う椎間板発生の仙骨脊索腫の一例

藤原智洋, 魚谷弘二, 国定俊之, 中田英二, 小田孔明, 三澤治夫, 尾崎敏文

中国・四国整形外科学会雑誌 35 ( 3 ) 423 - 423 2023.11

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