Updated on 2025/05/01

写真a

 
KUNISADA Toshiyuki
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Special-Appointment Professor
Position
Special-Appointment Professor
Other name(s)
国定俊之
External link

Research Interests

  • 関節外科学

  • 画像診断

  • 骨軟部腫瘍治療

  • 整形外科学

  • リハビリテーション

Research Areas

  • Life Science / Orthopedics

Education

  • Okayama University   医学研究科  

    - 1997

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    Country: Japan

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  • Nagasaki University   医学部  

    - 1993

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    Country: Japan

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Research History

  • 岡山大学学術研究院医歯薬学域   准教授

    2021.4

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  • 岡山大学医歯薬学総合研究科   准教授

    2007 - 2021

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  • Okayama University   整形外科

    2005 - 2007

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  • Okayama University   整形外科   Research Assistant

    2002 - 2005

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  • 岡山医療センター

    2001 - 2002

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Professional Memberships

 

Papers

  • Methotrexate, Doxorubicin, and Cisplatin Versus Methotrexate, Doxorubicin, and Cisplatin + Ifosfamide in Poor Responders to Preoperative Chemotherapy for Newly Diagnosed High-Grade Osteosarcoma (JCOG0905): A Multicenter, Open-Label, Randomized Trial

    Hiroaki Hiraga, Ryunosuke Machida, Akira Kawai, Toshiyuki Kunisada, Tsukasa Yonemoto, Makoto Endo, Yoshihiro Nishida, Akihito Nagano, Keisuke Ae, Shinichirou Yoshida, Kunihiro Asanuma, Junya Toguchida, Taisuke Furuta, Robert Nakayama, Toshihiro Akisue, Toru Hiruma, Takeshi Morii, Hideki Nishimura, Koji Hiraoka, Masanobu Takeyama, Makoto Emori, Satoshi Tsukushi, Hiroshi Hatano, Hiroyuki Kawashima, Kazuo Isu, Kazuhiro Tanaka, Tomoko Kataoka, Haruhiko Fukuda, Yukihide Iwamoto, Toshifumi Ozaki

    Journal of Clinical Oncology   2025.3

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    Publishing type:Research paper (scientific journal)   Publisher:American Society of Clinical Oncology (ASCO)  

    PURPOSE

    Our previous NECO phase II studies on high-grade osteosarcoma suggested that administering ifosfamide (IF; 16 g/m 2 [4g/m 2 once on day 1, then 2g/m 2 once on days 2-7] × six) to patients showing a poor response (PrRsp) to preoperative chemotherapy with methotrexate, doxorubicin, and cisplatin (MAP) improves their prognoses. In this Japan Clinical Oncology Group (JCOG) study, JCOG0905, we aimed to investigate the efficacy and safety of IF in patients with PrRsp.

    METHODS

    JCOG0905 is a multicenter, open-label, multi-institutional, randomized trial. Eligible patients (50 years and younger) had resectable, high-grade osteosarcoma (stage II or III, Union for International Cancer Control TNM) of the extremities, limb girdles, and thoracic wall. After two MAP cycles and tumor resection, patients with PrRsp were randomly assigned to either the MAP or MAP plus 15 g/m 2 (3g/m 2 once daily on days 1-5) × six IF (MAP + IF [MAPIF]) group. The primary end point was disease-free survival (DFS); secondary end points were overall survival (OS) and safety. The planned sample size was 100 patients with a one-sided α of .1 and a power of 0.7, assuming a 3-year DFS of 50% and 65% for MAP and MAPIF, respectively. This trial is registered with the Japan Registry of Clinical Trials (jRCT; jRCTs031180126).

    RESULTS

    Of the 287 patients registered between February 2010 and August 2020, 51 and 52 patients with PrRsp were assigned to the MAP and MAPIF groups, respectively. As of March 2022, DFS did not differ between groups (hazard ratio [HR], 1.05 [95% CI, 0.55 to 1.98]) and OS was numerically inferior in the MAPIF group (HR, 1.48 [95% CI, 0.68 to 3.22]). Nine and zero patients in the MAPIF and MAP groups discontinued treatment because of adverse events, respectively.

    CONCLUSION

    Evidence from JCOG0905 does not support the addition of IF for patients with PrRsp.

    DOI: 10.1200/jco-24-01281

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  • Empowering pediatric, adolescent, and young adult patients with cancer utilizing generative AI chatbots to reduce psychological burden and enhance treatment engagement: a pilot study

    Joe Hasei, Mana Hanzawa, Akihito Nagano, Naoko Maeda, Shinichirou Yoshida, Makoto Endo, Nobuhiko Yokoyama, Motoharu Ochi, Hisashi Ishida, Hideki Katayama, Tomohiro Fujiwara, Eiji Nakata, Ryuichi Nakahara, Toshiyuki Kunisada, Hirokazu Tsukahara, Toshifumi Ozaki

    Frontiers in Digital Health   7   2025.2

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    Publishing type:Research paper (scientific journal)   Publisher:Frontiers Media SA  

    Background

    Pediatric and adolescent/young adult (AYA) cancer patients face profound psychological challenges, exacerbated by limited access to continuous mental health support. While conventional therapeutic interventions often follow structured protocols, the potential of generative artificial intelligence (AI) chatbots to provide continuous conversational support remains unexplored. This study evaluates the feasibility and impact of AI chatbots in alleviating psychological distress and enhancing treatment engagement in this vulnerable population.

    Methods

    Two age-appropriate AI chatbots, leveraging GPT-4, were developed to provide natural, empathetic conversations without structured therapeutic protocols. Five pediatric and AYA cancer patients participated in a two-week intervention, engaging with the chatbots via a messaging platform. Pre- and post-intervention anxiety and stress levels were self-reported, and usage patterns were analyzed to assess the chatbots’ effectiveness.

    Results

    Four out of five participants reported significant reductions in anxiety and stress levels post-intervention. Participants engaged with the chatbot every 2–3 days, with sessions lasting approximately 10 min. All participants noted improved treatment motivation, with 80% disclosing personal concerns to the chatbot they had not shared with healthcare providers. The 24/7 availability particularly benefited patients experiencing nighttime anxiety.

    Conclusions

    This pilot study demonstrates the potential of generative AI chatbots to complement traditional mental health services by addressing unmet psychological needs in pediatric and AYA cancer patients. The findings suggest these tools can serve as accessible, continuous support systems. Further large-scale studies are warranted to validate these promising results.

    DOI: 10.3389/fdgth.2025.1543543

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  • Radiographic and Clinical Assessment of Unidirectional Porous Beta-Tricalcium Phosphate to Treat Benign Bone Tumors. International journal

    Toshiyuki Kunisada, Eiji Nakata, Tomohiro Fujiwara, Haruyoshi Katayama, Takuto Itano, Takanao Kurozumi, Teruhiko Ando, Toshifumi Ozaki

    Biomimetics (Basel, Switzerland)   10 ( 2 )   2025.2

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

    The purpose of this study was to evaluate radiographic changes, clinical outcomes, and complications following unidirectional porous beta-tricalcium phosphate (UDPTCP) implantation for the treatment of benign bone tumors. We retrospectively analyzed 46 patients who underwent intralesional resection. The patients were divided into two cohorts: Cohort 1 (n = 32), which included all bones except the phalanges and metacarpal/tarsal bones, and Cohort 2 (n = 14), which included the phalanges and metacarpal/tarsal bones. Radiographic changes were assessed at each reading based on resorption of the implanted UDPTCP and bone trabeculation through the defect. UDPTCP resorption and bone trabeculation were observed on radiographs within 3 months of surgery in all patients. Bone remodeling in the cavity progressed steadily for up to 3 years postoperatively. In Cohort 1, resorption and trabeculation progressed significantly in young patients, and trabeculation developed significantly in small lesions. The rates of resorption and trabeculation at 3 months postoperatively correlated statistically with their increased rates at one year. There was no statistical difference in resorption and trabeculation rates between Cohort 1 and Cohort 2. There were no cases of postoperative deep infections or allergic reactions related to the implant. UDPTCP is a useful bone-filling substitute for the treatment of benign bone tumors and has a low complication rate.

    DOI: 10.3390/biomimetics10020101

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  • Clinicopathological background of local recurrence in high grade sarcoma of the extremity with preoperative chemotherapy: a supplementary analysis of JCOG0304. International journal

    Satoshi Tsukushi, Kazuhiro Tanaka, Toshiyuki Kunisada, Ryunosuke Machida, Satoshi Takenaka, Akira Kawai, Hirohisa Katagiri, Masanobu Takeyama, Makoto Endo, Katsuhiro Hayashi, Robert Nakayama, Hiroshi Hatano, Makoto Emori, Shinichirou Yoshida, Toshio Kojima, Akio Sakamoto, Jungo Imanishi, Ryosuke Kita, Toshifumi Ozaki, Yukihide Iwamoto

    Japanese journal of clinical oncology   2025.2

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

    BACKGROUND: The mainstay of treatment for soft-tissue sarcomas is complete resection with negative surgical margins. However, treatment strategies for local control including the frequency of adjuvant radiotherapy (RT) and surgical margin differ greatly between Japan and other countries, and the optimal strategy of local control remains controversial. METHODS: A total of 70 patients with high-grade sarcoma who underwent surgery of the 72 patients enrolled in JCOG0304, were included. The primary endpoint was the proportion of local recurrence, and we investigated the clinicopathological background of local recurrence cases, including the surgical margins according to the Japanese Orthopedic Association (JOA) margin classification or histological margin, and use of adjuvant RT. RESULTS: Local recurrence occurred in five patients, with a 5-year local recurrence proportion of 7.1% (95% confidence interval, 2.6%-14.8%) in 70 patients. The histological subtype were four cases of undifferentiated pleomorphic sarcoma (UPS) and 1 case of liposarcoma. The 5-year local recurrence proportions for UPS and non-UPS were 19.0% and 2.0%, respectively. Two of the five recurrent cases (40%) had adjuvant RT. The recurrent cases were four males and one female, median age 54 years (range: 33-66), JOA margin classification showed wide resection in four cases and marginal resection in one case, and histological margin showed negative in all five cases. CONCLUSION: Despite the low proportion of adjuvant RT, local control of high-grade soft tissue sarcoma with preoperative chemotherapy in JCOG0304 was good. However, more detailed surgical margin evaluation and the use of adjuvant RT should be further investigated in the future for UPS.

    DOI: 10.1093/jjco/hyaf027

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  • The Three-Class Annotation Method Improves the AI Detection of Early-Stage Osteosarcoma on Plain Radiographs: A Novel Approach for Rare Cancer Diagnosis. International journal

    Joe Hasei, Ryuichi Nakahara, Yujiro Otsuka, Yusuke Nakamura, Kunihiro Ikuta, Shuhei Osaki, Tamiya Hironari, Shinji Miwa, Shusa Ohshika, Shunji Nishimura, Naoaki Kahara, Aki Yoshida, Tomohiro Fujiwara, Eiji Nakata, Toshiyuki Kunisada, Toshifumi Ozaki

    Cancers   17 ( 1 )   2024.12

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

    Background/Objectives: Developing high-performance artificial intelligence (AI) models for rare diseases is challenging owing to limited data availability. This study aimed to evaluate whether a novel three-class annotation method for preparing training data could enhance AI model performance in detecting osteosarcoma on plain radiographs compared to conventional single-class annotation. Methods: We developed two annotation methods for the same dataset of 468 osteosarcoma X-rays and 378 normal radiographs: a conventional single-class annotation (1C model) and a novel three-class annotation method (3C model) that separately labeled intramedullary, cortical, and extramedullary tumor components. Both models used identical U-Net-based architectures, differing only in their annotation approaches. Performance was evaluated using an independent validation dataset. Results: Although both models achieved high diagnostic accuracy (AUC: 0.99 vs. 0.98), the 3C model demonstrated superior operational characteristics. At a standardized cutoff value of 0.2, the 3C model maintained balanced performance (sensitivity: 93.28%, specificity: 92.21%), whereas the 1C model showed compromised specificity (83.58%) despite high sensitivity (98.88%). Notably, at the 25th percentile threshold, both models showed identical false-negative rates despite significantly different cutoff values (3C: 0.661 vs. 1C: 0.985), indicating the ability of the 3C model to maintain diagnostic accuracy at substantially lower thresholds. Conclusions: This study demonstrated that anatomically informed three-class annotation can enhance AI model performance for rare disease detection without requiring additional training data. The improved stability at lower thresholds suggests that thoughtful annotation strategies can optimize the AI model training, particularly in contexts where training data are limited.

    DOI: 10.3390/cancers17010029

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Books

  • 今日の整形外科治療指針 第8版

    国定俊之( Role: Contributor ,  Ewing 肉腫)

    医学書院  2021.10  ( ISBN:9784260042604

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    Total pages:xxvii, 964p   Responsible for pages:182   Language:Japanese

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  • 整形外科学レビュー 2021-'22

    国定 俊之, 中田 英二, 尾﨑 敏文( Role: Contributor ,  Ⅳ章 骨軟部 1 骨腫瘍 10-2. 原発性悪性骨腫瘍の治療指針)

    総合医学社  2021.3  ( ISBN:9784883787340

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    Total pages:281p   Responsible for pages:228-232   Language:Japanese

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  • がん患者の運動器疾患の診かた

    中田 英二, 国定 俊之, 尾﨑 敏文( Role: Joint author ,  骨転移の臨床症状とがんロコモ.)

    中外医学社  2019.10 

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    Responsible for pages:pp63-67   Language:Japanese

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  • スタンダード小児がん手術-臓器別アプローチと手技のポイント-

    国定 俊之, 藤原 智洋, 長谷井 嬢, 尾﨑 敏文( Role: Joint author ,  VI 術中の対応,処置 ナビゲーション手術:四肢,脊椎)

    メジカルビュー社  2017.8 

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    Responsible for pages:117-120   Language:Japanese

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  • New Mook 整形外科 18号

    尾﨑 敏文, 国定 俊之(腫瘍用人工関節による患肢温存手術)

    金原出版,東京  2005.4 

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    Responsible for pages:97-107  

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MISC

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Presentations

  • 術中 CT ナビゲーションを用いた類骨骨腫に対する低侵襲手術

    藤原 智洋, 国定 俊之, 中田 英二, 尾﨑 敏文

    第32回日本小児整形外科学会学術集会 

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    Event date: 2021.12.2 - 2021.12.3

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

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  • 類骨骨種に対する RFA

    冨田 晃司, 馬越 紀行, 宇賀 麻由, 藤原 智洋, 松井 裕輔, 中田 英二, 生口 俊浩, 国定 俊之, 平木 隆夫, 尾﨑 敏文

    第32回日本小児整形外科学会学術集会 

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    Event date: 2021.12.2 - 2021.12.3

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

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  • 術前がん患者におけるがんロコモ・サルコペニアの有病率

    堅山 佳美, 中田 英二, 濱田 全紀, 国定 俊之, 藤原 智洋, 千田 益生, 尾﨑 敏文

    第54回中国・四国整形外科学会 

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    Event date: 2021.11.20 - 2021.12.5

    Language:Japanese   Presentation type:Oral presentation (general)  

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  • 肉腫におけるがんゲノム医療の意義

    中田 英二, 国定 俊之, 藤原 智洋, 尾﨑 敏文

    第36回日本整形外科学会基礎学術集会 

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    Event date: 2021.10.14 - 2021.10.15

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  • Pexidartinib の骨肉腫に対する前臨床的検討: CSF-1/CSF-1R 阻害は肉腫微小環境の免疫細胞構成分画を変化させ抗腫瘍効果を発揮する

    藤原 智洋, 吉田 晶, 近藤 宏也, 畑 利彰, 佐藤 浩平, 棏平 将太, 中田 英二, 国定 俊之, 尾﨑 敏文, Yakoub M, Healey J

    第36回日本整形外科学会基礎学術集会 

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    Event date: 2021.10.14 - 2021.10.15

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Awards

  • 論文賞

    2005   第27回日本応用物理学会  

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  • 最優秀ポスター賞

    2004   第19回日本整形外科学会 基礎学術集会  

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  • 岡山医学会賞(山田賞)

    2000  

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    Country:Japan

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Research Projects

  • がん遺伝子パネル検査の全国登録データを利用した悪性骨軟部腫瘍の網羅的遺伝子解析

    Grant number:23K08632  2023.04 - 2026.03

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    國定 俊之, 中田 英二, 藤原 智洋

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    Grant amount:\4550000 ( Direct expense: \3500000 、 Indirect expense:\1050000 )

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  • Basic research for the establishment of adequate sequence of chemotherapy in the treatment of advanced soft tissue sarcoma

    Grant number:22K09436  2022.04 - 2025.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    山根 弘路, 中西 秀和, 瀧川 奈義夫, 國定 俊之, 越智 宣昭

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    Grant amount:\4030000 ( Direct expense: \3100000 、 Indirect expense:\930000 )

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  • 新規肉腫バイオマーカーを利用したリキッドバイオプシーの臨床応用

    Grant number:19K09650  2019.04 - 2022.03

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    國定 俊之

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    Grant amount:\4290000 ( Direct expense: \3300000 、 Indirect expense:\990000 )

    粘液線維肉腫(MFS)患者、非MFS肉腫患者、健常人の血清RNAを用いてmicroarray解析を行った。細胞株はNMFH-1、NMFH-2、およびヒト間葉系幹細胞(hMSC)を用いた。患者血清、細胞株培養上清由来RNA、NMFH-1の担癌マウス血清由来RNAを用いてqRT-PCR解析を行い、MFSにおける分泌型miRNAを検討した。microarray解析により5種類、qRT-PCRにより5種類のうち3種類のmiRNAが健常人よりMFS患者の血清において有意に高く発現していた。さらに術後にも低下するmiRNAを選別した。このmiRNAはMFS細胞株培養上清、担癌マウス血清においてcontrolと比較し有意に発現が高く、腫瘍サイズと有意な相関関係を認めた。次に、MFS細胞株培養上清より抽出したexosome分画の解析を行い、これらを用いmigration assay、ヒト由来正常線維芽細胞(NF)を用いたinvasion assayによる機能解析を行った。MFS細胞株培養上清由来exosome分画においてもその発現は高かった。migration assayではexosome投与による肉腫細胞自身の移動能増加は認めなかったが、invasion assayではNFに腫瘍由来exosomeを暴露した群でコントロール群より肉腫細胞の浸潤性が増強された。MFSの患者血清・培養上清から分泌型miRNAを特定し、新規バイオマーカーとなりうる可能性が示された。さらにこのmiRNAは肉腫由来exosomeに内包されることが示され、肉腫細胞自身に作用するのではなく、周囲正常細胞に作用することで易浸潤環境を作っていると考えられた。すなわち腫瘍由来exosomeによるパラクライン効果の存在が示唆された。

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  • Elucidation of the molecular mechanism of invasion and metastasis of human sarcomas via tumor-derived exosomes and its applicaion to novel therapies.

    Grant number:17K10969  2017.04 - 2020.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Morita Takuya

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    Grant amount:\4680000 ( Direct expense: \3600000 、 Indirect expense:\1080000 )

    Infiltrative tumor growth into adjacent soft tissues is a major cause of the frequent recurrence of sarcoma, and no useful biomarkers are available for tumor monitoring. The aim of the present study was to identify fibroblasts.
    Serum miRNA expression may represent a novel diagnostic target for monitoring of highly aggressive sarcoma. Furthermore, exosomal miRNA could act as a transfer messenger to adjacent cells and mediate the infiltrative nature of sarcoma, revealing a crosstalk between tumor cells and normal cells in the tumor microenvironment.

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  • Identification of diagnostic biomarker and novel fusion genes of bone and soft tissue sarcoma

    Grant number:16H02676  2016.04 - 2021.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)  Grant-in-Aid for Scientific Research (A)

    Matsuda Koichi

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    Grant amount:\46410000 ( Direct expense: \35700000 、 Indirect expense:\10710000 )

    In this research project, we conduced genome analysis and functional analysis of bone and soft tissue tumors to elucidate their molecular pathogenesis and developing new therapeutics. Through a collaborative network of Japan sarcoma genome consortium consisting of 28 medical institutions and 14 research institutes, pairs of tumor and normal tissue of 20 target diseases (dedifferentiated liposarcoma, giant synovial cell tumor, epithelial sarcoma, and osteoblastoma etc) were collected and RNA sequence and whole exome sequence of more than 400 samples was performed. As a result, CTDSP1 / 2-DNM3OS fusion (dedifferentiated liposarcoma) was identified as a disease-specific fusion gene. We also identified frequent CBL mutations in tenosynovial giant cell tumors and useful prognostic markers for Desmoid tumors.

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Class subject in charge

  • Locomotor System (2024academic year) special  - その他

  • Orthopaedic Surgery (2021academic year) 1st semester  - 月1

  • Orthopaedic Surgery (2020academic year) 1st semester  - 月1