2025/10/23 更新

写真a

ハセイ ジョウ
長谷井 嬢
HASEI Joe
所属
医歯薬学域 教授(特任)
職名
教授(特任)

学位

  • 医学博士 ( 2013年6月   岡山大学大学院 )

研究分野

  • ライフサイエンス / 整形外科学

  • 情報通信 / ロボティクス、知能機械システム

経歴

  • 岡山大学学術研究院医歯薬学域, 医療情報化診療支援技術開発講座   教授

    2024年9月 - 現在

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  • 岡山大学学術研究院医歯薬学域   医療情報化診療支援技術開発講座   准教授

    2022年9月 - 現在

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  • 岡山市立市民病院   整形外科   医長

    2020年10月 - 2022年8月

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  • 岡山大学大学院医歯薬学総合研究科   運動器スポーツ医学講座   助教

    2018年4月 - 2020年9月

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  • 岡山大学病院   整形外科   医員

    2016年4月 - 2018年3月

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  • スクリプス研究所   Professional Scientific Collaborator

    2015年4月 - 2016年3月

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    国名:アメリカ合衆国

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  • スクリプス研究所   Research Associate

    2014年2月 - 2015年3月

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    国名:アメリカ合衆国

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  • 岡山大学病院   整形外科   医員

    2012年4月 - 2014年1月

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  • 岡山大学大学院医歯薬学総合研究科 博士課程   Ph.D.

    2009年4月 - 2013年6月

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  • 岡山大学医学部・歯学部附属病院   整形外科   レジデント

    2009年4月 - 2012年3月

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  • 水和会 水島中央病院   初期研修医

    2007年4月 - 2009年3月

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  • 杏林大学医学部医学科卒業

    2007年3月

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▼全件表示

 

論文

  • Mohawk is a transcription factor that promotes meniscus cell phenotype and tissue repair and reduces osteoarthritis severity. 査読 国際誌

    Kwang Il Lee, Ramya Gamini, Merissa Olmer, Yasunari Ikuta, Joe Hasei, Jihye Baek, Oscar Alvarez-Garcia, Shawn P Grogan, Darryl D D'Lima, Hiroshi Asahara, Andrew I Su, Martin K Lotz

    Science translational medicine   12 ( 567 )   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Meniscus tears are common knee injuries and a major osteoarthritis (OA) risk factor. Knowledge gaps that limit the development of therapies for meniscus injury and degeneration concern transcription factors that control the meniscus cell phenotype. Analysis of RNA sequencing data from 37 human tissues in the Genotype-Tissue Expression database and RNA sequencing data from meniscus and articular cartilage showed that transcription factor Mohawk (MKX) is highly enriched in meniscus. In human meniscus cells, MKX regulates the expression of meniscus marker genes, OA-related genes, and other transcription factors, including Scleraxis (SCX), SRY Box 5 (SOX5), and Runt domain-related transcription factor 2 (RUNX2). In mesenchymal stem cells (MSCs), the combination of adenoviral MKX (Ad-MKX) and transforming growth factor-β3 (TGF-β3) induced a meniscus cell phenotype. When Ad-MKX-transduced MSCs were seeded on TGF-β3-conjugated decellularized meniscus scaffold (DMS) and inserted into experimental tears in meniscus explants, they increased glycosaminoglycan content, extracellular matrix interconnectivity, cell infiltration into the DMS, and improved biomechanical properties. Ad-MKX injection into mouse knee joints with experimental OA induced by surgical destabilization of the meniscus suppressed meniscus and cartilage damage, reducing OA severity. Ad-MKX injection into human OA meniscus tissue explants corrected pathogenic gene expression. These results identify MKX as a previously unidentified key transcription factor that regulates the meniscus cell phenotype. The combination of Ad-MKX with TGF-β3 is effective for differentiation of MSCs to a meniscus cell phenotype and useful for meniscus repair. MKX is a promising therapeutic target for meniscus tissue engineering, repair, and prevention of OA.

    DOI: 10.1126/scitranslmed.aan7967

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  • Utility of Same-Modality, Cross-Domain Transfer Learning for Malignant Bone Tumor Detection on Radiographs: A Multi-Faceted Performance Comparison with a Scratch-Trained Model

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

    Cancers   2025年9月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/cancers17193144

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  • Metaverse Support Groups for LGBTQ+ Youth: An Observational Study on Safety, Self-Expression, and Early Intervention 査読

    Joe Hasei

    Journal of Metaverse   abs/2507.21079   2025年6月

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    担当区分:筆頭著者, 責任著者   掲載種別:研究論文(学術雑誌)  

    DOI: 10.48550/arXiv.2507.21079

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  • Osteosarcoma cell-derived CCL2 facilitates lung metastasis via accumulation of tumor-associated macrophages. 国際誌

    Hiroya Kondo, Hiroshi Tazawa, Tomohiro Fujiwara, Aki Yoshida, Miho Kure, Koji Demiya, Nobuhiko Kanaya, Toshiaki Hata, Koji Uotani, Joe Hasei, Toshiyuki Kunisada, Shunsuke Kagawa, Yusuke Yoshioka, Toshifumi Ozaki, Toshiyoshi Fujiwara

    Cancer immunology, immunotherapy : CII   74 ( 7 )   193 - 193   2025年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Osteosarcoma (OS) is the most common malignant tumor of bone in children and adolescents. Although lung metastasis is a major obstacle to improving the prognosis of OS patients, the underlying mechanism of lung metastasis of OS is poorly understood. Tumor-associated macrophages (TAMs) with M2-like characteristics are reportedly associated with lung metastasis and poor prognosis in OS patients. In this study, we investigated the metastasis-associated tumor microenvironment (TME) in orthotopic OS tumor models with non-metastatic and metastatic OS cells. Non-metastatic and metastatic tumor cells derived from mouse OS (Dunn and LM8) and human OS (HOS and 143B) were used to analyze the TME associated with lung metastasis in orthotopic OS tumor models. OS cell-derived secretion factors were identified by cytokine array and enzyme-linked immunosorbent assay (ELISA). Orthotopic tumor models with metastatic LM8 and 143B cells were analyzed to evaluate the therapeutic potential of a neutralizing antibody in the development of primary and metastatic tumors. Metastatic OS cells developed metastatic tumors with infiltration of M2-like TAMs in the lungs. Cytokine array and ELISA demonstrated that metastatic mouse and human OS cells commonly secreted CCL2, which was partially encapsulated in extracellular vesicles. In vivo experiments demonstrated that while primary tumor growth was unaffected, administration of CCL2-neutralizing antibody led to a significant suppression of lung metastasis and infiltration of M2-like TAMs in the lung tissue. Our results suggest that CCL2 plays a crucial role in promoting the lung metastasis of OS cells via accumulation of M2-like TAMs.

    DOI: 10.1007/s00262-025-04051-x

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  • Comparative analysis of a standard (GPT-4o) and reasoning-enhanced (o1 pro) large language model on complex clinical questions from the Japanese orthopaedic board examination. 査読

    Joe Hasei, Ryuichi Nakahara, Koichi Takeuchi, Aki Yoshida, Takuto Itano, Tomohiro Fujiwara, Eiji Nakata, Toshiyuki Kunisada, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   30 ( 3 )   565 - 568   2025年5月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jos.2025.03.005

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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 査読 国際誌

    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   1543543 - 1543543   2025年2月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元: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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  • The Three-Class Annotation Method Improves the AI Detection of Early-Stage Osteosarcoma on Plain Radiographs: A Novel Approach for Rare Cancer Diagnosis 査読 国際誌

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

    Cancers   17 ( 1 )   2024年12月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    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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  • Identification of ENO-1 positive extracellular vesicles as a circulating biomarker for monitoring of Ewing sarcoma. 国際誌

    Koji Uotani, Tomohiro Fujiwara, Koji Ueda, Aki Yoshida, Shintaro Iwata, Takuya Morita, Masahiro Kiyono, Toshiyuki Kunisada, Ken Takeda, Joe Hasei, Yusuke Yoshioka, Takahiro Ochiya, Toshifumi Ozaki

    Cancer science   115 ( 11 )   3660 - 3671   2024年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The lack of circulating biomarkers for tumor monitoring is a major problem in Ewing sarcoma management. The development of methods for accurate tumor monitoring is required, considering the high recurrence rate of drug-resistant Ewing sarcoma. Here, we describe a sensitive analytical technique for tumor monitoring of Ewing sarcoma by detecting circulating extracellular vesicles secreted from Ewing sarcoma cells. Proteomic analysis of Ewing sarcoma cell-derived extracellular vesicles identified 564 proteins prominently observed in extracellular vesicles from three Ewing sarcoma cell lines. Among these, CD99, SLC1A5, and ENO-1 were identified on extracellular vesicles purified from sera of patients with Ewing sarcoma before treatment but not on extracellular vesicles from those after treatment and healthy individuals. Notably, not only Ewing sarcoma-derived extracellular vesicles but also Ewing sarcoma cells demonstrated proteomic expression of CD99 and ENO-1 on their surface membranes. ENO-1+CD63+ extracellular vesicle detection was reduced after tumor resection while both CD99+CD63+ and ENO-1+CD63+ extracellular vesicles were detected in serum from Ewing sarcoma-bearing mice. Finally, the accuracy of liquid biopsy targeting these candidates was assessed using extracellular vesicles from the sera of patients with Ewing sarcoma. Elevated ENO-1+CD81+ extracellular vesicles in the serum of patients before treatments distinguished patients with Ewing sarcoma from healthy individuals with an area under the curve value of 0.92 (P < 0.001) and reflected the tumor burden in patients with Ewing sarcoma during multidisciplinary treatments. Collectively, circulating ENO-1+CD81+ extracellular vesicle detection could represent a novel tool for tumor monitoring of Ewing sarcoma.

    DOI: 10.1111/cas.16343

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  • p53-armed oncolytic virotherapy induces abscopal effect in osteosarcoma by promoting immunogenic cell death. 査読 国際誌

    Koji Demiya, Hiroshi Tazawa, Hiroya Kondo, Miho Kure, Yusuke Mochizuki, Tadashi Komatsubara, Aki Yoshida, Koji Uotani, Joe Hasei, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

    Molecular therapy. Oncology   32 ( 3 )   200845 - 200845   2024年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Osteosarcoma (OS), the most frequent primary malignant tumor of bone in children and adolescents, is refractory to immune checkpoint inhibitors due to its poor antitumor immune response. Chemotherapy and virotherapy induce immunogenic cell death (ICD) and antitumor immune responses, leading to the abscopal effect in untreated tumors. We previously demonstrated the antitumor activity of the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 in human OS cells. Here, we show the therapeutic potential of chemotherapeutic drugs (doxorubicin, cisplatin) and telomerase-specific oncolytic adenoviruses (OBP-301, p53-armed OBP-702) to induce ICD in human OS cells (U2OS, MNNG/HOS, SaOS-2) and murine OS cells (NHOS). OBP-702 induced more profound ICD via the secretion of adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1) compared with chemotherapy and OBP-301 in human OS cells. Murine NHOS cells were also more sensitive to OBP-702 than OBP-301. Subcutaneous NHOS tumor models demonstrated that intratumoral injection of OBP-702 significantly increased the tumor infiltration of cytotoxic CD8+ T cells and induced the abscopal effect against non-treated tumors compared with OBP-301. Our results suggest that OBP-702 is a promising antitumor reagent to induce ICD with secretion of ATP and HMGB1 and the abscopal effect against OS.

    DOI: 10.1016/j.omton.2024.200845

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  • High-quality expert annotations enhance artificial intelligence model accuracy for osteosarcoma X-ray diagnosis. 査読 国際誌

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

    Cancer science   115 ( 11 )   3695 - 3704   2024年9月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Primary malignant bone tumors, such as osteosarcoma, significantly affect the pediatric and young adult populations, necessitating early diagnosis for effective treatment. This study developed a high-performance artificial intelligence (AI) model to detect osteosarcoma from X-ray images using highly accurate annotated data to improve diagnostic accuracy at initial consultations. Traditional models trained on unannotated data have shown limited success, with sensitivities of approximately 60%-70%. In contrast, our model used a data-centric approach with annotations from an experienced oncologist, achieving a sensitivity of 95.52%, specificity of 96.21%, and an area under the curve of 0.989. The model was trained using 468 X-ray images from 31 osteosarcoma cases and 378 normal knee images with a strategy to maximize diversity in the training and validation sets. It was evaluated using an independent dataset of 268 osteosarcoma and 554 normal knee images to ensure generalizability. By applying the U-net architecture and advanced image processing techniques such as renormalization and affine transformations, our AI model outperforms existing models, reducing missed diagnoses and enhancing patient outcomes by facilitating earlier treatment. This study highlights the importance of high-quality training data and advocates a shift towards data-centric AI development in medical imaging. These insights can be extended to other rare cancers and diseases, underscoring the potential of AI in transforming diagnostic processes in oncology. The integration of this AI model into clinical workflows could support physicians in early osteosarcoma detection, thereby improving diagnostic accuracy and patient care.

    DOI: 10.1111/cas.16330

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  • Utilizing the Metaverse to Provide Innovative Psychosocial Support for Pediatric, Adolescent, and Young Adult Patients with Rare Cancer 査読 国際誌

    Joe Hasei, Hisashi Ishida, Hideki Katayama, Naoko Maeda, Akihito Nagano, Motoharu Ochi, Masako Okamura, Shintaro Iwata, Kunihiro Ikuta, Shinichirou Yoshida, Tomohiro Fujiwara, Eiji Nakata, Ryuichi Nakahara, Toshiyuki Kunisada, Toshifumi Ozaki

    Cancers   16 ( 15 )   2617 - 2617   2024年7月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    This study investigated the potential of the metaverse in providing psychological support for pediatric and AYA cancer patients, with a focus on those with rare cancers. The research involved ten cancer patients and survivors from four distinct regions in Japan, who participated in metaverse sessions using customizable avatars, facilitating interactions across geographical and temporal barriers. Surveys and qualitative feedback were collected to assess the psychosocial impact of the intervention. The results demonstrated that the metaverse enabled patients to connect with peers, share experiences, and receive emotional support. The anonymity provided by avatars helped reduce appearance-related anxiety and stigma associated with cancer treatment. A case study of a 19-year-old male with spinal Ewing’s sarcoma highlighted the profound emotional relief fostered by metaverse interactions. The findings suggest that integrating virtual spaces into healthcare models can effectively address the unique needs of pediatric and AYA cancer patients, offering a transformative approach to delivering psychosocial support and fostering a global patient community. This innovative intervention has the potential to revolutionize patient care in the digital age.

    DOI: 10.3390/cancers16152617

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  • 大規模言語モデルの外部文書読み込み(RAG)を用いた医療文書の自動Q&A開発

    那須 義久, 竹内 孔一, 中原 龍一, 長谷井 嬢, 西田 圭一郎, 尾崎 敏文

    日本関節病学会誌   43 ( 2 )   251 - 251   2024年6月

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    記述言語:日本語   出版者・発行元:(一社)日本関節病学会  

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  • マルチモーダル大規模言語を用いた自動病理画像解析

    中原 龍一, 竹内 孔一, 那須 義久, 長谷井 嬢, 高橋 康, 西田 圭一郎, 尾崎 敏文

    日本関節病学会誌   43 ( 2 )   252 - 252   2024年6月

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    記述言語:日本語   出版者・発行元:(一社)日本関節病学会  

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  • p53-Armed Oncolytic Virotherapy Improves Radiosensitivity in Soft-Tissue Sarcoma by Suppressing BCL-xL Expression. 査読

    Tadashi Komatsubara, Hiroshi Tazawa, Joe Hasei, Toshinori Omori, Kazuhisa Sugiu, Yusuke Mochizuki, Koji Demiya, Aki Yoshida, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

    Acta medica Okayama   78 ( 2 )   151 - 161   2024年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities including radiotherapy, STSs are often refractory to antitumor modalities, and novel strategies that improve the prognosis of STS patients are needed. We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. Here, we demonstrate in vitro and in vivo antitumor effects of OBP-702 in combination with ionizing radiation against human STS cells (HT1080, NMS-2, SYO-1). OBP-702 synergistically promoted the antitumor effect of ionizing radiation in the STS cells by suppressing the expression of B-cell lymphoma-X large (BCL-xL) and enhancing ionizing radiation-induced apoptosis. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors' growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors.

    DOI: 10.18926/AMO/66924

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  • Fluorescence-guided assessment of bone and soft-tissue sarcomas for predicting the efficacy of telomerase-specific oncolytic adenovirus. 査読 国際誌

    Koji Uotani, Hiroshi Tazawa, Joe Hasei, Tomohiro Fujiwara, Aki Yoshida, Yasuaki Yamakawa, Toshinori Omori, Kazuhisa Sugiu, Tadashi Komatsubara, Hiroya Kondo, Takuya Morita, Masahiro Kiyono, Suguru Yokoo, Toshiaki Hata, Toshiyuki Kunisada, Ken Takeda, Yasuo Urata, Toshiyoshi Fujiwara, Toshifumi Ozaki

    PloS one   19 ( 2 )   e0298292   2024年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Bone and soft-tissue sarcomas are rare malignancies with histological diversity and tumor heterogeneity, leading to the lack of a common molecular target. Telomerase is a key enzyme for keeping the telomere length and human telomerase reverse transcriptase (hTERT) expression is often activated in most human cancers, including bone and soft-tissue sarcomas. For targeting of telomerase-positive tumor cells, we developed OBP-301, a telomerase-specific replication-competent oncolytic adenovirus, in which the hTERT promoter regulates adenoviral E1 gene for tumor-specific viral replication. In this study, we present the diagnostic potential of green fluorescent protein (GFP)-expressing oncolytic adenovirus OBP-401 for assessing virotherapy sensitivity using bone and soft-tissue sarcomas. OBP-401-mediated GFP expression was significantly associated with the therapeutic efficacy of OBP-401 in human bone and soft-tissue sarcomas. In the tumor specimens from 68 patients, malignant and intermediate tumors demonstrated significantly higher expression levels of coxsackie and adenovirus receptor (CAR) and hTERT than benign tumors. OBP-401-mediated GFP expression was significantly increased in malignant and intermediate tumors with high expression levels of CAR and hTERT between 24 and 48 h after infection. Our results suggest that the OBP-401-based GFP expression system is a useful tool for predicting the therapeutic efficacy of oncolytic virotherapy on bone and soft-tissue sarcomas.

    DOI: 10.1371/journal.pone.0298292

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  • Computer assisted orthopaedic surgeryがもたらす整形外科の次世代診療 希少疾患に対するAI開発戦略

    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   97 ( 8 )   S1783 - S1783   2023年8月

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    担当区分:筆頭著者, 責任著者   記述言語:日本語   出版者・発行元:(公社)日本整形外科学会  

    J-GLOBAL

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  • LRRC15 expression indicates high level of stemness regulated by TWIST1 in mesenchymal stem cells. 査読 国際誌

    Kensuke Toriumi, Yuta Onodera, Toshiyuki Takehara, Tatsufumi Mori, Joe Hasei, Kanae Shigi, Natsumi Iwawaki, Toshifumi Ozaki, Masao Akagi, Mahito Nakanishi, Takeshi Teramura

    iScience   26 ( 7 )   106946 - 106946   2023年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Mesenchymal stem cells (MSCs) are used as a major source for cell therapy, and its application is expanding in various diseases. On the other hand, reliable method to evaluate quality and therapeutic properties of MSC is limited. In this study, we focused on TWIST1 that is a transcription factor regulating stemness of MSCs and found that the transmembrane protein LRRC15 tightly correlated with the expression of TWIST1 and useful to expect TWIST1-regulated stemness of MSCs. The LRRC15-positive MSC populations in human and mouse bone marrow tissues highly expressed stemness-associated transcription factors and therapeutic cytokines, and showed better therapeutic effect in bleomycin-induced pulmonary fibrosis model mice. This study provides evidence for the important role of TWIST1 in the MSC stemness, and for the utility of the LRRC15 protein as a marker to estimate stem cell quality in MSCs before cell transplantation.

    DOI: 10.1016/j.isci.2023.106946

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  • 骨盤悪性骨腫瘍に対する股関節包内切除術と包外切除術の腫瘍学的予後および機能的予後の比較検討

    藤原 智洋, Stevenson Jonathan, Parry Michael, Grimer Robert, 津田 祐輔, 長谷井 嬢, 中田 英二, 国定 俊之, 尾崎 敏文, Jeys Lee

    日本整形外科学会雑誌   97 ( 6 )   S1443 - S1443   2023年6月

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    記述言語:日本語   出版者・発行元:(公社)日本整形外科学会  

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  • 骨・軟部腫瘍診療におけるデジタルトランスフォーメーションとプレシジョン・メディシン AIを用いた骨肉腫X線読影における転移学習の効果

    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   97 ( 3 )   S611 - S611   2023年3月

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    記述言語:日本語   出版者・発行元:(公社)日本整形外科学会  

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  • Measurement of Lag-Screw Anteversion With an iPhone During Trochanteric Fracture Surgery 査読 国際誌

    Yo Kinami, Joe Hasei, Kazuo Fujiwara

    Cureus   14 ( 12 )   e33110   2022年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Cureus, Inc.  

    Introduction  A useful way to easily evaluate femoral rotation during surgery for trochanteric fractures is not known. Hence, this pilot study aimed to develop an intraoperative indicator to evaluate anteversion in femoral trochanteric fractures. Material and methods Prospectively, from June 2021 to January 2022, all patients with femoral trochanteric fractures (Orthopaedic Trauma Association classification: 31A1-3) treated using a cephalo-medullary nail with a lag-screw neck-shaft angle of 125° were included in this study. During surgery, lag-screw anteversion (LS-AV) was measured using the goniometer application in an iPhone with the fractured femur table-top-plane level with the traction table floor. Accuracy was analyzed by comparing axial-projected lag-screw anteversion (AxP-LS-AV) and three-dimensional computed tomography lag-screw anteversion (3DCT-LS-AV) measurements after surgery. Results Fifty patients (14 males and 36 females) were included in the study. The mean age was 87 (range; 69-98) years; the Orthopaedic Trauma Association classifications were A1 (28 patients), A2 (18 patients), and A3 (4 patients). The mean LS-AV was 10.7° ± 6.9°, the mean AxP-LS-AV was 12.8° ± 8.3°, and the mean 3DCT-LS-AV was 13.1° ± 8.6°. The median difference between AxP-LS-AV and 3DCT-LS-AV was 3.0° (range: 0°-12°), and 40 (80%) patients had differences of ≤5° (Bland-Altman plot: inside of limit of agreement = 86%, paired t-test p = 0.7, Pearson correlation coefficient r = 0.817, p <0.001). Conclusion Femur malrotation is defined as a deformity of >15° relative to the normal contralateral limb. Intraoperative LS-AV iPhone measurement on table-top-plane standard had sufficient accuracy as an indicator of anteversion in femoral trochanteric fractures.

    DOI: 10.7759/cureus.33110

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  • AIと診断・治療 AIによる骨肉腫X線読影システムの偽陽性対策

    長谷井 嬢, 中原 龍一, 藤原 智洋, 中田 英二, 国定 俊之, 木浪 陽, 藤原 一夫, 臼井 正明, 尾崎 敏文

    日本整形外科学会雑誌   96 ( 8 )   S1741 - S1741   2022年9月

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    記述言語:日本語   出版者・発行元:(公社)日本整形外科学会  

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  • AIを用いた骨端線の年齢変化の学習と単純X線画像自動生成

    中原 龍一, 西田 圭一郎, 長谷井 嬢, 中澤 慎二, 韓 昌煕, 藏品 豊, 那須 義久, 尾崎 敏文

    日本整形外科学会雑誌   96 ( 2 )   S427 - S427   2022年3月

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    記述言語:日本語   出版者・発行元:(公社)日本整形外科学会  

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  • BAPGAN: GAN-based bone age progression of femur and phalange x-ray images. 査読

    Shinji Nakazawa, Changhee Han, Joe Hasei, Ryuichi Nakahara, Toshifumi Ozaki

    Medical Imaging: Computer-Aided Diagnosis   2022年

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    掲載種別:研究論文(国際会議プロシーディングス)  

    DOI: 10.1117/12.2608065

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    その他リンク: https://dblp.uni-trier.de/db/conf/micad/micad2022.html#NakazawaHHNO22

  • AIを用いた単純X線画像における骨端線変化の自動生成

    中原 龍一, 西田 圭一郎, 長谷井 嬢, 中澤 慎二, 韓 昌煕, 藏品 豊, 那須 義久, 尾崎 敏文

    日本関節病学会誌   40 ( 3 )   308 - 308   2021年11月

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    記述言語:日本語   出版者・発行元:(一社)日本関節病学会  

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  • Sub-deltoid approach for removal of large lipoma around the proximal humerus: A report of three cases. 査読

    Joe Hasei, Toshiyuki Kunisada, Eiji Nakata, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   26 ( 6 )   1147 - 1151   2021年11月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jos.2018.12.030

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  • Oncolytic virotherapy reverses chemoresistance in osteosarcoma by suppressing MDR1 expression. 査読 国際誌

    Kazuhisa Sugiu, Hiroshi Tazawa, Joe Hasei, Yasuaki Yamakawa, Toshinori Omori, Tadashi Komatsubara, Yusuke Mochizuki, Hiroya Kondo, Shuhei Osaki, Tomohiro Fujiwara, Aki Yoshida, Toshiyuki Kunisada, Koji Ueda, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

    Cancer chemotherapy and pharmacology   88 ( 3 )   513 - 524   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Osteosarcoma (OS) is a malignant bone tumor primarily affecting children and adolescents. The prognosis of chemotherapy-refractory OS patients is poor. We developed a tumor suppressor p53-expressing oncolytic adenovirus (OBP-702) that exhibits antitumor effects against human OS cells. Here, we demonstrate the chemosensitizing effect of OBP-702 in human OS cells. MATERIALS AND METHODS: The in vitro and in vivo antitumor activities of doxorubicin (DOX) and OBP-702 were assessed using parental and DOX-resistant OS cells (U2OS, MNNG/HOS) and a DOX-resistant MNNG/HOS xenograft tumor model. RESULTS: DOX-resistant OS cells exhibited high multidrug resistant 1 (MDR1) expression, which was suppressed by OBP-702 or MDR1 siRNA, resulting in enhanced DOX-induced apoptosis. Compared to monotherapy, OBP-702 and DOX combination therapy significantly suppressed tumor growth in the DOX-resistant MNNG/HOS xenograft tumor model. CONCLUSION: Our results suggest that MDR1 is an attractive therapeutic target for chemoresistant OS. Tumor-specific virotherapy is thus a promising strategy for reversing chemoresistance in OS patients via suppression of MDR1 expression.

    DOI: 10.1007/s00280-021-04310-5

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  • Telomerase-specific oncolytic immunotherapy for promoting efficacy of PD-1 blockade in osteosarcoma. 査読 国際誌

    Yusuke Mochizuki, Hiroshi Tazawa, Koji Demiya, Miho Kure, Hiroya Kondo, Tadashi Komatsubara, Kazuhisa Sugiu, Joe Hasei, Aki Yoshida, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

    Cancer immunology, immunotherapy : CII   70 ( 5 )   1405 - 1417   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Immune checkpoint inhibitors including anti-programmed cell death 1 (PD-1) antibody have recently improved clinical outcome in certain cancer patients; however, osteosarcoma (OS) patients are refractory to PD-1 blockade. Oncolytic virotherapy has emerged as novel immunogenic therapy to augment antitumor immune response. We developed a telomerase-specific replication-competent oncolytic adenovirus OBP-502 that induces lytic cell death via binding to integrins. In this study, we assessed the combined effect of PD-1 blockade and OBP-502 in OS cells. The expression of coxsackie and adenovirus receptor (CAR), integrins αvβ3 and αvβ5, and programmed cell death ligand 1 (PD-L1) was analyzed in two murine OS cells (K7M2, NHOS). The cytopathic activity of OBP-502 in both cells was analyzed using the XTT assay. OBP-502-induced immunogenic cell death was assessed by analyzing the level of extracellular ATP and high-mobility group box protein B1 (HMGB1). Subcutaneous tumor models for K7M2 and NHOS cells were used to evaluate the antitumor effect and number of tumor-infiltrating CD8+ cells in combination therapy. K7M2 and NHOS cells showed high expression of integrins αvβ3 and αvβ5, but not CAR. OBP-502 significantly suppressed the viability of both cells, in which PD-L1 expression and the release of ATP and HMGB1 were significantly increased. Intratumoral injection of OBP-502 significantly augmented the efficacy of PD-1 blockade on subcutaneous K2M2 and NHOS tumor models via enhancement of tumor-infiltrating CD8+  T cells. Our results suggest that telomerase-specific oncolytic virotherapy is a promising antitumor strategy to promote the efficacy of PD-1 blockade in OS.

    DOI: 10.1007/s00262-020-02774-7

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  • Liquid Biopsy Targeting Monocarboxylate Transporter 1 on the Surface Membrane of Tumor-Derived Extracellular Vesicles from Synovial Sarcoma. 査読 国際誌

    Suguru Yokoo, Tomohiro Fujiwara, Aki Yoshida, Koji Uotani, Takuya Morita, Masahiro Kiyono, Joe Hasei, Eiji Nakata, Toshiyuki Kunisada, Shintaro Iwata, Tsukasa Yonemoto, Koji Ueda, Toshifumi Ozaki

    Cancers   13 ( 8 )   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The lack of noninvasive biomarkers that can be used for tumor monitoring is a major problem for soft-tissue sarcomas. Here we describe a sensitive analytical technique for tumor monitoring by detecting circulating extracellular vesicles (EVs) of patients with synovial sarcoma (SS). The proteomic analysis of purified EVs from SYO-1, HS-SY-II, and YaFuSS identified 199 common proteins. DAVID GO analysis identified monocarboxylate transporter 1 (MCT1) as a surface marker of SS-derived EVs, which was also highly expressed in SS patient-derived EVs compared with healthy individuals. MCT1+CD9+ EVs were also detected from SS-bearing mice and their expression levels were significantly correlated with tumor volume (p = 0.003). Furthermore, serum levels of MCT1+CD9+ EVs reflected tumor burden in SS patients. Immunohistochemistry revealed that MCT1 was positive in 96.7% of SS specimens and its expression on the cytoplasm/plasma membrane was significantly associated with worse overall survival (p = 0.002). Silencing of MCT1 reduced the cellular viability, and migration and invasion capability of SS cells. This work describes a new liquid biopsy technique to sensitively monitor SS using circulating MCT1+CD9+ EVs and indicates the therapeutic potential of MCT1 in SS.

    DOI: 10.3390/cancers13081823

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  • BAPGAN: GAN-based Bone Age Progression of Femur and Phalange X-ray Images.

    Shinji Nakazawa, Changhee Han, Joe Hasei, Ryuichi Nakahara, Toshifumi Ozaki

    CoRR   abs/2110.08509   2021年

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    掲載種別:研究論文(学術雑誌)  

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    その他リンク: https://dblp.uni-trier.de/db/journals/corr/corr2110.html#abs-2110-08509

  • Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression. 国際誌

    Toshinori Omori, Hiroshi Tazawa, Yasuaki Yamakawa, Shuhei Osaki, Joe Hasei, Kazuhisa Sugiu, Tadashi Komatsubara, Tomohiro Fujiwara, Aki Yoshida, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

    PloS one   16 ( 4 )   e0250643   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Soft tissue sarcoma (STS) is a rare cancer that develops from soft tissues in any part of the body. Despite major advances in the treatment of STS, patients are often refractory to conventional radiotherapy, leading to poor prognosis. Enhancement of sensitivity to radiotherapy would therefore improve the clinical outcome of STS patients. We previously revealed that the tumor-specific, replication-competent oncolytic adenovirus OBP-301 kills human sarcoma cells. In this study, we investigated the radiosensitizing effect of OBP-301 in human STS cells. The in vitro antitumor effect of OBP-301 and ionizing radiation in monotherapy or combination therapy was assessed using highly radiosensitive (RD-ES and SK-ES-1) and moderately radiosensitive (HT1080 and NMS-2) STS cell lines. The expression of markers for apoptosis and DNA damage were evaluated in STS cells after treatment. The therapeutic potential of combination therapy was further analyzed using SK-ES-1 and HT1080 cells in subcutaneous xenograft tumor models. The combination of OBP-301 and ionizing radiation showed a synergistic antitumor effect in all human STS cell lines tested, including those that show different radiosensitivity. OBP-301 was found to enhance irradiation-induced apoptosis and DNA damage via suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1), which was expressed at higher levels in moderately radiosensitive cell lines. The combination of OBP-301 and ionizing radiation showed a more profound antitumor effect compared to monotherapy in SK-ES-1 (highly radiosensitive) and HT1080 (moderately radiosensitive) subcutaneous xenograft tumors. OBP-301 is a promising antitumor reagent to improve the therapeutic potential of radiotherapy by increasing radiation-induced apoptosis in STS.

    DOI: 10.1371/journal.pone.0250643

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  • Pyoderma gangrenosum complicated by myopathy after tumor resection surgery: a rare case report. 査読

    Joe Hasei, Toshiyuki Kunisada, Eiji Nakata, Toshifumi Ozaki

    Ann Case Report.   6 ( 1 )   645   2021年

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    担当区分:筆頭著者   記述言語:英語  

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  • Radiographic and clinical assessment of unidirectional porous hydroxyapatite to treat benign bone tumors. 国際誌

    Toshiyuki Kunisada, Joe Hasei, Tomohiro Fujiwara, Eiji Nakata, Suguru Yokoo, Koji Demiya, Toshifumi Ozaki

    Scientific reports   10 ( 1 )   21578 - 21578   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Unidirectional porous hydroxyapatite (UDPHAp) was developed as an excellent scaffold with unidirectional pores oriented in the horizontal direction with interpore connections. The purpose of this study was to assess radiographic changes and clinical outcomes and complications following UDPHAp implantation to treat benign bone tumors. We retrospectively analyzed 44 patients treated with intralesional resection and UDPHAp implantation for benign bone tumors between 2010 and 2015. Clinical and radiographic findings were evaluated postoperatively at regular follow-up visits. The mean follow-up was 49 months. Radiographic changes were classified into five stages based on bone formation in the implanted UDPHAp according to Tamai's classification. All patients showed excellent bone formation inside and around implanted UDPHAp. Absorption of UDPHAp and bone marrow cavity remodeling was identified in 20 patients at a mean of 17 months postoperatively, and was significantly more common in young patients. Preoperative cortical thinning was completely regenerated in 26 of 31 patients on average 10 months after surgery. There were no cases of delayed wound healing, postoperative infection, or allergic reaction related to implanted UDPHAp. UDPHAp is a useful bone-filling substitute for treating benign bone tumor, and the use of this material has a low complication rate.

    DOI: 10.1038/s41598-020-78409-9

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  • What Are the Results of Resection of Localized Dedifferentiated Liposarcomas in the Extremities? 国際誌

    Eiji Nakata, Toshiyuki Kunisada, Joe Hasei, Ryuichi Nakahara, Hiroyuki Yanai, Tomohiro Toji, Hirofumi Inoue Ct, Toshifumi Ozaki

    Clinical orthopaedics and related research   478 ( 11 )   2550 - 2561   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Dedifferentiated liposarcoma (DDLPS) is a rare malignancy that transitions from an atypical lipomatous tumor to a sarcoma with a variable morphologic appearance. The behavior of this tumor in the retroperitoneum is aggressive, but the behavior of DDLPS in the extremities is less well-defined because it is rare. Few reports have assessed the imaging features and clinical outcomes of primary DDLPS in the extremities. QUESTIONS/PURPOSES: In patients with primary DDLPS of the extremity, we asked the following questions: (1) How frequently do additional primary malignancies occur in patients with DDLPS? (2) What is the rate of overall survival, metastases, and local recurrence in DDLPS? (3) What factors are associated with metastasis-free survival and local recurrence in DDLPS? METHODS: We defined DDLPS as a biphasic neoplasm that transitions from an atypical lipomatous tumor (ALT) to a sarcoma of variable morphologic appearance and histologic grades. We retrospectively evaluated the medical records of patients with DDLPS of the extremities who underwent surgery in our institution between 2003 and 2017. During that time, 16 patients were treated for this diagnosis; one was excluded from this study because the patient did not have an MRI, leaving 15 patients (nine men, six women; their median [range] age was 67 years [42 to 87]) for evaluation. All had a minimum of 2 years follow-up (median [range] 54 months [25 to 136]); 14 of 15 have been seen in the last 5 years (one patient, who was doing well at the time, was lost after 9 years of follow-up). In 11 patients, MRI demonstrated two components: an ALT component with high intensity on both T1-weighed and T2-weighted sequences and a dedifferentiated component low-to-intermediate intensity on T1-weighed and heterogeneous hyperintensity on T2-weighted sequence. Nine patients were evaluated using 2-deoxy-2-18F-fluoro-D-glucose positron emission tomography (FDG-PET) combined with CT (PET/CT). PET/CT showed a biphasic pattern with a close relationship to MRI findings. The dedifferentiated component presented with high FDG uptake (median [range] maximum standardized uptake value 5.1 [1.9 to 22.6]), while the atypical lipomatous tumor component showed almost no FDG uptake. In all patients, immunohistochemical studies of p16 and cyclin-dependent kinase-4 (CDK4) were investigated. Positive staining for both p16 and CDK4 were seen in 13 of 15 patients.We retrospectively evaluated the electronic medical records of all patients in our institution for the presence of additional primary malignancies, local recurrence-free survival, metastasis-free survival, and overall survival. The survival rate was estimated using the Kaplan-Meier method. The Wilcoxon exact test was used to determine the prognostic importance of the following survival variables: age, sex, maximum tumor size, radiotherapy, and surgical margin. RESULTS: Seven additional primary malignancies developed in five of 15 patients (two lung cancers, two sarcomas, one renal cell cancer, one uterine cancer, and one non-Hodgkin lymphoma). The 3- and 5-year metastasis-free survival rates were 86% (95% CI 0.67 to 1.00) and 75% (95% CI 0.49 to 1.00), respectively. With the numbers available, we found no factors associated with metastasis-free survival. The 3- and 5-year overall survival rates were 100% (95% CI 1.00 to 1.00) and 88% (95% CI 0.65 to 1.00), respectively. Three of 15 patients had local recurrence. The 3- and 5-year local recurrence-free survival rates were 86% (95% CI 0.67 to 1.00) and 75% (95% CI 0.49 to 1.00), respectively. Large (> 15 cm) tumors were more likely to have a local recurrence (p = 0.04). CONCLUSIONS: In this small series, we found that the extremities are a favorable site for DDLPS compared with the retroperitoneum, although we did not directly compare the two sites. This rare tumor has a relatively high likelihood of being associated with other malignancies. We believe patients should be assessed and monitored carefully for this possibility. In the future, larger studies are needed to better define predictors of local recurrence, although the tumor's size may be associated with a greater propensity for local recurrence. LEVEL OF EVIDENCE: Level II, prognostic study.

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  • Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma. 国際誌

    Takuya Morita, Tomohiro Fujiwara, Aki Yoshida, Koji Uotani, Masahiro Kiyono, Suguru Yokoo, Joe Hasei, Toshiyuki Kunisada, Toshifumi Ozaki

    Scientific reports   10 ( 1 )   9414 - 9414   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Infiltrative tumor growth into adjacent soft tissues is a major cause of the frequent recurrence and tumor-related death of myxofibrosarcoma (MFS), but no useful biomarkers reflecting tumor burden and infiltrative growth are available. While emerging evidence suggests a diagnostic and functional role of extracellular/circulating microRNA (miRNA) in various malignant diseases, their significance in MFS patients remains unknown. Global miRNA profiling identified four upregulated miRNAs in MFS patient sera and culture media of MFS cells. Among these, serum miR-1260b level was significantly upregulated in patient serum discriminating from healthy individuals and closely correlated with clinical status and tumor dynamics in MFS-bearing mice. In addition, high miR-1260b expression in serum was correlated with radiological tail-like patterns, characteristic of the infiltrative MFS. The extracellular miR-1260b was embedded in tumor-derived extracellular vesicles (EVs) and promoted cellular invasion of MFS through the downregulation of PCDH9 in the adjacent normal fibroblasts. Collectively, circulating miR-1260b expression may represent a novel diagnostic target for tumor monitoring of this highly aggressive sarcoma. Moreover, EV-miR-1260b could act as a transfer messenger to adjacent cells and mediate the infiltrative growth of MFS, providing new insights into the mechanism of infiltrative nature via crosstalk between tumor cells and their microenvironment.

    DOI: 10.1038/s41598-020-66120-8

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  • Bone and Soft-Tissue Sarcoma: A New Target for Telomerase-Specific Oncolytic Virotherapy. 国際誌

    Hiroshi Tazawa, Joe Hasei, Shuya Yano, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

    Cancers   12 ( 2 )   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Adenovirus serotype 5 (Ad5) is widely and frequently used as a virus vector in cancer gene therapy and oncolytic virotherapy. Oncolytic virotherapy is a novel antitumor treatment for inducing lytic cell death in tumor cells without affecting normal cells. Based on the Ad5 genome, we have generated three types of telomerase-specific replication-competent oncolytic adenoviruses: OBP-301 (Telomelysin), green fluorescent protein (GFP)-expressing OBP-401 (TelomeScan), and tumor suppressor p53-armed OBP-702. These viruses drive the expression of the adenoviral E1A and E1B genes under the control of the hTERT (human telomerase reverse transcriptase-encoding gene) promoter, providing tumor-specific virus replication. This review focuses on the therapeutic potential of three hTERT promoter-driven oncolytic adenoviruses against bone and soft-tissue sarcoma cells with telomerase activity. OBP-301 induces the antitumor effect in monotherapy or combination therapy with chemotherapeutic drugs via induction of autophagy and apoptosis. OBP-401 enables visualization of sarcoma cells within normal tissues by serving as a tumor-specific labeling reagent for fluorescence-guided surgery via induction of GFP expression. OBP-702 exhibits a profound antitumor effect in OBP-301-resistant sarcoma cells via activation of the p53 signaling pathway. Taken together, telomerase-specific oncolytic adenoviruses are promising antitumor reagents that are expected to provide novel therapeutic options for the treatment of bone and soft-tissue sarcomas.

    DOI: 10.3390/cancers12020478

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  • Molecular radiosensitization of soft tissue sarcoma by oncolytic virus-mediated MCL1 ablation

    Omori T, Tazawa H, Yamakawa Y, Osaki S, Hasei J, Sugiu K, Komatsubara T, Fujiwara T, Yoshida A, Kunisada T, Urata Y, Kagawa S, Ozaki T, Fujiwara T

    2020年1月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.21203/rs.2.20608/v1

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  • Temporary External Fixation Can Stabilize Hip Transposition Arthroplasty After Resection of Malignant Periacetabular Bone Tumors. 国際誌

    Toshiyuki Kunisada, Tomohiro Fujiwara, Joe Hasei, Eiji Nakata, Masuo Senda, Toshifumi Ozaki

    Clinical orthopaedics and related research   477 ( 8 )   1892 - 1901   2019年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The choice of reconstructive procedure to restore limb function is challenging after internal hemipelvectomy. Hip transposition arthroplasty, also known as resection arthroplasty, removes a malignant or aggressive tumor of the pelvis and acetabulum after which the remaining femoral head is moved proximally to the lateral surface side of the sacrum or the underside of the resected ilium after internal hemipelvectomy. It may provide reasonable functional results and have some advantages such as lowering the risk of an infected implant compared with other reconstructions because no foreign implants are used. Hip transposition is generally managed with prolonged bed rest or immobilization postoperatively to stabilize the soft tissue surrounding the remaining femur. Because enabling patients to be mobile while the soft tissues heal might be advantageous, we reviewed our experience with an external fixation for this procedure. QUESTIONS/PURPOSES: (1) Does temporary external fixation facilitate postoperative physiotherapy in patients who undergo hip transposition arthroplasty? (2) What functional Musculoskeletal Tumor Society (MSTS) scores were achieved at short term in a small series of patients treated with hip transposition and temporary external fixation? (3) What were the complications of using external fixation in a small series of patients who received it for malignant tumors? METHODS: Between 2008 and 2012, we treated seven patients (three men and four women; median age, 37 years; age range, 18-53 years) with acetabular resection for malignant bone tumors; all were managed with a hip transposition, initially stabilized using external fixation. No other types of procedures were used for this indication in this period. Minimum followup in this retrospective study was 45 months, except for one patient who died at 18 months (range of followup duration, 18-90 months; median followup, 57 months), and no patients were lost to followup. The pins for external fixation were inserted into the affected side of the femur and the healthy contralateral ilium. External fixation was removed 6 weeks postoperatively and weightbearing was started at that time. Preoperative chemotherapy was administrated in four patients, but postoperative chemotherapy was delayed since it was given after external fixation removal in three patients. The postoperative rehabilitation course and functional results were assessed by chart review, functional results were determined using MSTS scores, tallied by physiotherapists who were not part of the surgical team, and complications were ascertained through chart review. Major complications were defined as complications that were treated with additional operations, such as deep infection, or ones that could cause severe postoperative dysfunction, such as nerve injury. RESULTS: With temporary external fixation, standing next to a bed was achieved in median 7 days (range, 6-9 days) postoperatively, transferring to a wheel chair in median 8 days (range, 6-28 days), and gait training using parallel bars in median 15 days (range, 7-48 days). At most recent followup, three patients could walk without a crutch or cane, three could walk with a cane, and one could walk with a crutch. The median MSTS score at most recent followup (median, 57 months) was 63%. Two patients had complications that resulted in reoperations; one had a wound dehiscence, and one had an abdominal herniation that gradually developed, and which was reconstructed using polypropylene mesh 2 years after pelvic resection. Two patients had nerve palsies that recovered by the end of the first year. All patients had pin tract infections that resolved with nonsurgical approaches. CONCLUSIONS: Hip transposition with temporary external fixation can stabilize the bone soft tissue after pelvic resection. Although we did not have a comparison group of patients, we believe that external fixation facilitates early postoperative physiotherapy and rehabilitation and provides good functional results without major surgical complications. Because it delays the resumption of chemotherapy, more patients with longer followup are needed to determine whether this will be associated with poorer oncologic results. LEVEL OF EVIDENCE: Level IV, therapeutic study.

    DOI: 10.1097/CORR.0000000000000764

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  • Involvement of ADAM12 in Chondrocyte Differentiation by Regulation of TGF-β1-Induced IGF-1 and RUNX-2 Expressions. 国際誌

    Masahiro Horita, Keiichiro Nishida, Joe Hasei, Takayuki Furumatsu, Miwa Sakurai, Yuta Onodera, Kanji Fukuda, Donald M Salter, Toshifumi Ozaki

    Calcified tissue international   105 ( 1 )   97 - 106   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A disintegrin and metalloproteinase 12 (ADAM12) is known to be involved in chondrocyte proliferation and maturation; however, the mechanisms are not fully understood. In this study, expression and localization of ADAM12 during chondrocyte differentiation were examined in the mouse growth plate by immunohistochemistry. Adam12 expression during ATDC5 chondrogenic differentiation was examined by real-time PCR and compared with the expression pattern of type X collagen. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system was used to generate Adam12-knockout (KO) ATDC5 cells. Adam12-KO and Adam12 overexpressing cells were used for analyses of ADAM12 expression with or without TGF-β1 stimulation. ADAM12 was identified predominantly in chondrocytes of the proliferative zone in mouse growth plates by immunohistochemistry. Adam12 was upregulated prior to Col10a1 during chondrogenic differentiation in wild-type ATDC5 cells. In Adam12-KO ATDC5 cells, following initiation of chondrogenic differentiation, we observed a reduction in Igf-1 expression along with an upregulation of hypertrophy-associated Runx2, Col10a1, and type X collagen protein expressions. In ATDC5 wild-type cells, stimulation with TGF-β1 upregulated the expressions of Adam12 and Igf-1 and downregulated the expression of Runx2. In contrast, in Adam12-KO ATDC5 cells, these TGF-β1-induced changes were suppressed. Adam12 overexpression resulted in an upregulation of Igf-1 and downregulation of Runx2 expression in ATDC5 cells. The findings suggest that ADAM12 has important role in the regulation of chondrocyte differentiation, potentially by regulation of TGF-β1-dependent signaling and that targeting of ADAM12 may have a role in management of abnormal chondrocyte differentiation.

    DOI: 10.1007/s00223-019-00549-6

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  • Mini-open excision of osteoid osteoma using intraoperative O-arm/Stealth navigation.

    Tomohiro Fujiwara, Toshiyuki Kunisada, Ken Takeda, Joe Hasei, Eiji Nakata, Yusuke Mochizuki, Masahiro Kiyono, Aki Yoshida, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   24 ( 2 )   337 - 341   2019年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Although osteoid osteomas have traditionally been treated by surgical excision, radiofrequency ablation (RFA) has gained favor as a less invasive procedure. However, RFA is contraindicated for osteoid osteomas close to the skin or crucial neurovascular structures, and is not covered by national health insurance in Japan. The aim of the present study was to evaluate the efficacy of surgical excision of osteoid osteomas using intraoperative navigation. METHODS: We performed a retrospective review of five patients with osteoid osteoma who underwent a mini-open excision using O-arm/Stealth navigation at our institution. The osteoid osteomas were excised using a cannulated cutter or curetted out with the assistance of navigation. RESULTS: Complete excision was achieved in all patients, which was confirmed by pathological examination. The mean skin incision was 2.1 cm (range, 1.5 to 3.0 cm) and the mean duration required for setup three-dimensional image was 15 min (range, 12 to 20 min). Although the mean visual analog scale score was 7 (range, 4 to 8) before surgery, all patients experienced relief from their characteristic pain immediately after surgery, with the mean scores of 2.2 (range, 1 to 3) and 0 at 2 days and 4 weeks after surgery, respectively. There was no intra-operative complication related to the navigation and no recurrence was observed during the mean follow-up period of 25 months (range, 13 to 33 months). CONCLUSIONS: Mini-open excision using intraoperative O-arm/Stealth navigation is a safe and accurate procedure for patients with osteoid osteoma, which could cover the limitation of RFA.

    DOI: 10.1016/j.jos.2018.09.017

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  • A rare manifestation of extraskeletal myxoid chondrosarcoma with a huge expanding hematoma.

    Toshinori Omori, Tomohiro Fujiwara, Toshiyuki Kunisada, Ken Takeda, Joe Hasei, Aki Yoshida, Hiroyuki Yanai, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   24 ( 2 )   377 - 381   2019年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.jos.2016.12.011

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  • Injury patterns of medial meniscus posterior root tears. 国際誌

    Takayuki Furumatsu, Yuki Okazaki, Yoshiki Okazaki, Tomohito Hino, Yusuke Kamatsuki, Shin Masuda, Shinichi Miyazawa, Eiji Nakata, Joe Hasei, Toshiyuki Kunisada, Toshifumi Ozaki

    Orthopaedics & traumatology, surgery & research : OTSR   105 ( 1 )   107 - 111   2019年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: Medial meniscus posterior root tear (MMPRT) can occur in middle-aged patients who have a posteromedial painful popping during light activities. MMPRTs are more common in patients with increased age, female gender, sedentary lifestyle, obesity, and varus knee alignment. However, injury mechanisms of minor traumatic MMPRTs are still unclear. We hypothesized that high flexion activities are the major cause of MMPRTs. The aim of this study was to clarify injury patterns of MMPRTs. MATERIALS AND METHODS: One hundred patients were diagnosed having MMPRTs after posteromedial painful popping episodes. Details of posteromedial painful popping episode, situation of injury, and position of injured leg were obtained from the patients by careful interviews. Injury patterns were divided into 8 groups: descending knee motion, walking, squatting, standing up action, falling down, twisting, light exercise, and minor automobile accident. RESULTS: A descending knee motion was the most common cause of MMPRTs (38%) followed by a walking injury pattern (18%) and a squatting action related to high flexion activities of the knee (13%). The other injury patterns were less than 10%. DISCUSSION: Descending knee motions associated with descending stairs, step, and downhill slope are the most common injury pattern of MMPRTs. High flexion activities of the knee are not the greatest cause of MMPRTs. Our results suggest that the descending action with a low knee flexion angle may trigger minor traumatic MMPRTs. LEVEL OF EVIDENCE: IV, retrospective cohort study.

    DOI: 10.1016/j.otsr.2018.10.001

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  • Regeneration of the Fibula with Unidirectional Porous Hydroxyapatite. 国際誌

    Koji Demiya, Toshiyuki Kunisada, Eiji Nakata, Joe Hasei, Toshifumi Ozaki

    Case reports in orthopedics   2019   9024643 - 9024643   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A fibula graft is one of the most common orthopedic procedures for reconstruction of a bone defect, and some complications related to persistent defects of the fibula have been reported previously. We believe that regeneration of the fibula may be critical for postoperative function and prevention of complications. This report describes a 9-year-old female with Ewing sarcoma of the pelvis who was treated with the double-barrel fibula grafts for pelvic bone defect following tumor resection. The defect after fibular resection was filled with unidirectional porous hydroxyapatite (UDPHAp) implants. A plain radiograph revealed new bone formation and a callus-like structure at one month after surgery and bony union between each UDPHAp implant 5 months after surgery. Resorption of implanted UDPHAp was identified, and partial remodeling of the bone marrow cavity could be seen 1 year 2 months after surgery. A radiograph at final follow-up (5 years 10 months after surgery) demonstrated almost complete absorption of the implanted UDPHAp and clear formation of the cortex and bone marrow in the resected part of the fibula. The patient is able to walk well without any walking supports and to take part in sports activities.

    DOI: 10.1155/2019/9024643

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  • Injury patterns of medial meniscus posterior root tears,Traumatisme causal des lésions de la racine postérieure du ménisque médial

    Furumatsu, T., Okazaki, Y., Okazaki, Y., Hino, T., Kamatsuki, Y., Masuda, S., Miyazawa, S., Nakata, E., Hasei, J., Kunisada, T., Ozaki, T.

    Revue De Chirurgie Orthopedique Et Traumatologique   105 ( 1 )   58 - 58   2019年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.rcot.2018.10.008

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  • Identification of Circulating Exosomal Marker in Synovial Sarcoma

    Suguru Yokoo, Tomohiro Fujiwara, Aki Yoshida, Masahiro Kiyono, Yusuke Mochizuki, Koji Demiya, Joe Hasei, Toshiyuki Kunisada, Yusuke Yoshioka, Koji Ueda, Takahiro Ochiya, Toshifumi Ozaki

    CANCER SCIENCE   109   570 - 570   2018年12月

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    記述言語:英語  

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  • Intraoperative O-arm-navigated resection in musculoskeletal tumors.

    Tomohiro Fujiwara, Toshiyuki Kunisada, Ken Takeda, Joe Hasei, Eiji Nakata, Ryuichi Nakahara, Aki Yoshida, Toshifumi Ozaki

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   23 ( 6 )   1045 - 1050   2018年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Although emerging evidence has suggested that computer-assisted navigation allows surgeons to plan the optimal level of resection without compromising the surgical margins, the precise accuracy of the procedures has been unclear. The aim of this study was to investigate the accuracy and safety of the musculoskeletal tumor resection using O-arm/Stealth intraoperative navigation assistance. METHODS: A retrospective study of six patients with bone and soft tissue tumors who underwent surgical resection using O-arm/Stealth navigation system was performed. The histological diagnosis was osteosarcoma, metastatic bone tumor, leiomyosarcoma, undifferentiated sarcoma, and synovial sarcoma, respectively. Tumor resection was performed according to planned osteotomy planes determined on O-arm/Stealth three-dimensional intraoperative images. The resection accuracy, length of time for the procedures, surgical margins, and perioperative complications were evaluated. RESULTS: The distances between the entry and exit points for the planned and actual cuts were 1.5 ± 0.3 mm and 2.3 ± 0.3 mm, respectively, and the mean discrepancy of the osteotomy angle was 2.8 ± 1.2°. The mean length of time required for navigation was 14 min. A histological examination revealed clear margins in all patients. There were no complications related to navigation, and no patients developed local recurrence during a mean follow-up of 30.6 months. CONCLUSIONS: The O-arm/Stealth intraoperative CT navigation system provides safe and accurate osteotomy in musculoskeletal tumor resections. However, surgeons should keep in mind and be careful of minimal errors during osteotomy, which are around 2 mm from the planned line.

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  • Clinical and Functional Significance of Intracellular and Extracellular microRNA-25-3p in Osteosarcoma.

    Aki Yoshida, Tomohiro Fujiwara, Koji Uotani, Takuya Morita, Masahiro Kiyono, Suguru Yokoo, Joe Hasei, Eiji Nakata, Toshiyuki Kunisada, Toshifumi Ozaki

    Acta medica Okayama   72 ( 2 )   165 - 174   2018年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Although there is considerable evidence indicating that the dysregulation of microRNAs (miRNAs) in malignant tumors plays a role in tumor development, the overall function of miRNAs and their clinicopathological significance are not well understood. In this retrospective analysis of 45 biopsy specimens from osteosarcoma (OS) patients, we investigated the functional and clinical significance of miR-25-3p in OS, which we previously identified as a highly expressed miRNA in OS patients' serum. We observed that miR-25-3p dysregulation in human OS tissues was negatively correlated with the clinical prognosis, whereas the expression level of its target gene, Dickkopf WNT Signaling Pathway Inhibitor 3 (DKK3), was positively correlated with the clinical prognosis. Endogenous miR-25-3p upregulation promoted tumor growth, invasion, and drug resistance, which was consistent with DKK3 silencing in OS cells. In addition, secretory miR-25-3p was embedded in tumor-derived exosomes, where it promoted capillary formation and the invasion of vascular endothelial cells. Overall, our results show that miR-25-3p has intracellular and extracellular oncogenic functions as well as clinicopathological relevance in OS, indicating its potential as a novel diagnostic and therapeutic tool for the clinical management of this disease.

    DOI: 10.18926/AMO/55857

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  • 肉腫進行例の新しい診療システム サルコーマセンター設立と腫瘍内科医との連携

    国定 俊之, 田端 雅弘, 山根 弘路, 中田 英二, 長谷井 嬢, 尾崎 敏文

    中部日本整形外科災害外科学会雑誌   61 ( 春季学会 )   88 - 88   2018年3月

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    記述言語:日本語   出版者・発行元:(一社)中部日本整形外科災害外科学会  

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  • Liquid biopsy using tumor-derived exosomes for Ewing sarcoma patients

    Aki Yoshida, Tomohiro Fujiwara, Koji Uotani, Shintaro Iwata, Yusuke Yoshioka, Koji Ueda, Takuya Morita, Masahiro Kiyono, Suguru Yokoo, Joe Hasei, Toshiyuki Kunisada, Takahiro Ochiya, Toshifumi Ozaki

    CANCER SCIENCE   109   312 - 312   2018年1月

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    記述言語:英語  

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  • Circulating MicroRNA-92b-3p as a Novel Biomarker for Monitoring of Synovial Sarcoma. 国際誌

    Koji Uotani, Tomohiro Fujiwara, Aki Yoshida, Shintaro Iwata, Takuya Morita, Masahiro Kiyono, Suguru Yokoo, Toshiyuki Kunisada, Ken Takeda, Joe Hasei, Kunihiko Numoto, Yutaka Nezu, Tsukasa Yonemoto, Takeshi Ishii, Akira Kawai, Takahiro Ochiya, Toshifumi Ozaki

    Scientific reports   7 ( 1 )   14634 - 14634   2017年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The lack of useful biomarkers is a crucial problem for patients with soft tissue sarcomas (STSs). Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel impact as biomarkers for patients with malignant diseases, but their significance in synovial sarcoma (SS) patients remains unknown. Initial global miRNA screening using SS patient serum and SS cell culture media identified a signature of four upregulated miRNAs. Among these candidates, miR-92b-3p secretion from SS cells was confirmed, which was embedded within tumour-derived exosomes rather than argonaute-2. Animal experiments revealed a close correlation between serum miR-92b-3p levels and tumour dynamics. Clinical relevance was validated in two independent clinical cohorts, and we subsequently identified that serum miR-92b-3p levels were significantly higher in SS patients in comparison to that in healthy individuals. Moreover, serum miR-92b-3p was robust in discriminating patients with SS from the other STS patients and reflected tumour burden in SS patients. Overall, liquid biopsy using serum miR-92b-3p expression levels may represent a novel approach for monitoring tumour dynamics of SS.

    DOI: 10.1038/s41598-017-12660-5

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  • Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction. 国際誌

    Yasuaki Yamakawa, Hiroshi Tazawa, Joe Hasei, Shuhei Osaki, Toshinori Omori, Kazuhisa Sugiu, Tadashi Komatsubara, Kouji Uotani, Tomohiro Fujiwara, Aki Yoshida, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

    Cancer science   108 ( 9 )   1870 - 1880   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Osteosarcoma is an aggressive malignant bone tumor that causes bone destruction. Although tumor-specific replicating oncolytic adenovirus OBP-301 induces an antitumor effect in an osteosarcoma tumor, it cannot prevent bone destruction. Zoledronic acid (ZOL) is a clinically available agent that inhibits bone destruction. In this study, we investigated the potential of combination therapy with OBP-301 and ZOL against osteosarcomas with bone destruction. The antitumor activity of OBP-301 and ZOL in monotherapy or combination therapy was assessed using three human osteosarcoma cell lines (143B, MNNG/HOS, SaOS-2). The cytotoxic effect of OBP-301 and/or ZOL was measured by assay of cell apoptosis. The effect of OBP-301 and ZOL on osteoclast activation was investigated. The potential of combination therapy against tumor growth and bone destruction was analyzed using an orthotopic 143B osteosarcoma xenograft tumor model. OBP-301 and ZOL decreased the viability of human osteosarcoma cells. Combination therapy with OBP-301 and ZOL displayed a synergistic antitumor effect, in which OBP-301 promoted apoptosis through suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1). Combination therapy significantly inhibited tumor-mediated osteoclast activation, tumor growth and bone destruction compared to monotherapy. These results suggest that combination therapy of OBP-301 and ZOL suppresses osteosarcoma progression via suppression of MCL1 and osteoclast activation.

    DOI: 10.1111/cas.13316

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  • 軟骨分化制御による骨棘形成過程へのADAM12の関与

    堀田 昌宏, 西田 圭一郎, 長谷井 嬢, 古松 毅之, 宮澤 慎一, 那須 義久, 中原 龍一, 竹下 歩, 兼田 大輔, 大橋 秀基, 尾崎 敏文

    日本整形外科学会雑誌   91 ( 8 )   S1597 - S1597   2017年8月

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    記述言語:日本語   出版者・発行元:(公社)日本整形外科学会  

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  • Impact of Autophagy in Oncolytic Adenoviral Therapy for Cancer. 国際誌

    Hiroshi Tazawa, Shinji Kuroda, Joe Hasei, Shunsuke Kagawa, Toshiyoshi Fujiwara

    International journal of molecular sciences   18 ( 7 )   2017年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Oncolytic virotherapy has recently emerged as a promising strategy for inducing tumor-specific cell death. Adenoviruses are widely and frequently used in oncolytic virotherapy. The mechanism of oncolytic adenovirus-mediated tumor suppression involves virus-induced activation of the autophagic machinery in tumor cells. Autophagy is a cytoprotective process that produces energy via lysosomal degradation of intracellular components as a physiologic response to various stresses, including hypoxia, nutrient deprivation, and disruption of growth signaling. However, infection with oncolytic adenoviruses induces autophagy and subsequent death of tumor cells rather than enhancing their survival. In this review, we summarize the beneficial role of autophagy in oncolytic adenoviral therapy, including the roles of infection, replication, and cell lysis. Numerous factors are involved in the promotion and inhibition of oncolytic adenovirus-mediated autophagy. Furthermore, recent evidence has shown that oncolytic adenoviruses induce autophagy-related immunogenic cell death (ICD), which enhances the antitumor immune response by inducing the activation of danger signal molecules and thus represents a novel cancer immunotherapy. Understanding the precise role of oncolytic adenovirus-induced autophagy and ICD could enhance the therapeutic potential of oncolytic adenoviral therapy for treating various cancers.

    DOI: 10.3390/ijms18071479

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  • Inflammation-induced miRNA-155 inhibits self-renewal of neural stem cells via suppression of CCAAT/enhancer binding protein β (C/EBPβ) expression. 国際誌

    Kayoko Obora, Yuta Onodera, Toshiyuki Takehara, John Frampton, Joe Hasei, Toshifumi Ozaki, Takeshi Teramura, Kanji Fukuda

    Scientific reports   7   43604 - 43604   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Intracerebral inflammation resulting from injury or disease is implicated in disruption of neural regeneration and may lead to irreversible neuronal dysfunction. Analysis of inflammation-related microRNA profiles in various tissues, including the brain, has identified miR-155 among the most prominent miRNAs linked to inflammation. Here, we hypothesize that miR-155 mediates inflammation-induced suppression of neural stem cell (NSC) self-renewal. Using primary mouse NSCs and human NSCs derived from induced pluripotent stem (iPS) cells, we demonstrate that three important genes involved in NSC self-renewal (Msi1, Hes1 and Bmi1) are suppressed by miR-155. We also demonstrate that suppression of self-renewal genes is mediated by the common transcription factor C/EBPβ, which is a direct target of miR-155. Our study describes an axis linking inflammation and miR-155 to expression of genes related to NSC self-renewal, suggesting that regulation of miR-155 may hold potential as a novel therapeutic strategy for treating neuroinflammatory diseases.

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  • TWIST1 induces MMP3 expression through up-regulating DNA hydroxymethylation and promotes catabolic responses in human chondrocytes 査読

    Joe Hasei, Takeshi Teramura, Toshiyuki Takehara, Yuta Onodera, Takuro Horii, Merissa Olmer, Izuho Hatada, Kanji Fukuda, Toshifumi Ozaki, Martin K. Lotz, Hiroshi Asahara

    Scientific Reports   7   42990   2017年2月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/srep42990

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  • Ablation of MCL1 expression by virally induced microRNA-29 reverses chemoresistance in human osteosarcomas. 国際誌

    Shuhei Osaki, Hiroshi Tazawa, Joe Hasei, Yasuaki Yamakawa, Toshinori Omori, Kazuhisa Sugiu, Tadashi Komatsubara, Tomohiro Fujiwara, Tsuyoshi Sasaki, Toshiyuki Kunisada, Aki Yoshida, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

    Scientific reports   6   28953 - 28953   2016年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Osteosarcoma is a rare disease diagnosed as malignant bone tumor. It is generally refractory to chemotherapy, which contributes to its poor prognosis. The reversal of chemoresistance is a major clinical challenge to improve the prognostic outcome of osteosarcoma patients. We developed a tumor-specific replication-competent oncolytic adenovirus, OBP-301 (telomelysin) and assessed its synergistic effects with chemotherapeutic agents (cisplatin and doxorubicin) using human osteosarcoma cell lines and a xenograft tumor model. The molecular mechanism underlying the chemosensitizing effect of OBP-301 was evaluated in aspects of apoptosis induction. OBP-301 inhibits anti-apoptotic myeloid cell leukemia 1 (MCL1) expression, which in turn leads to chemosensitization in human osteosarcoma cells. The siRNA-mediated knockdown of MCL1 expression sensitized human osteosarcoma cells to common chemotherapeutic agents. We also found that upregulation of microRNA-29 targeting MCL1 via virally induced transcriptional factor E2F-1 activation was critical for the enhancement of chemotherapy-induced apoptosis in osteosarcoma cells. Telomerase-specific oncolytic adenovirus synergistically suppressed the viability of human osteosarcoma cells in combination with chemotherapeutic agents. The combination treatment also significantly inhibited tumor growth, as compared to monotherapy, in an osteosarcoma xenograft tumor model. Our data suggest that replicative virus-mediated tumor-specific MCL1 ablation may be a promising strategy to attenuate chemoresistance in osteosarcoma patients.

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  • 上腕骨近位部発生の悪性骨腫瘍に対する患肢温存術の治療成績

    武田 健, 国定 俊之, 大森 敏規, 上原 健敬, 山川 泰明, 尾崎 修平, 長谷井 嬢, 尾崎 敏文

    日本整形外科学会雑誌   88 ( 6 )   S1134 - S1134   2014年6月

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    記述言語:日本語   出版者・発行元:(公社)日本整形外科学会  

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  • 神経線維腫症1型に合併した巨大血腫に対して動脈塞栓術による止血を行った2例

    武田 健, 篠原 健介, 長谷井 嬢, 平木 隆夫, 国定 俊之, 尾崎 敏文

    日本整形外科学会雑誌   88 ( 6 )   S1252 - S1252   2014年6月

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    記述言語:日本語   出版者・発行元:(公社)日本整形外科学会  

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  • 骨盤Ewing肉腫に対して創外固定術を併用し腓骨移植術(non-vascularized)で再建した1例

    大森 敏規, 武田 健, 上原 健敬, 山川 泰明, 長谷井 嬢, 吉田 晶, 国定 俊之, 尾崎 敏文

    日本整形外科学会雑誌   88 ( 6 )   S1294 - S1294   2014年6月

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    記述言語:日本語   出版者・発行元:(公社)日本整形外科学会  

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  • 骨・軟部腫瘍切除術時のstaple使用は創合併症に影響しない

    国定 俊之, 上原 健敬, 武田 健, 長谷井 嬢, 山川 泰明, 井上 円加, 尾崎 敏文

    日本整形外科学会雑誌   88 ( 6 )   S1242 - S1242   2014年6月

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    記述言語:日本語   出版者・発行元:(公社)日本整形外科学会  

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  • 大腿骨遠位骨幹部骨折偽関節(infraisthmal fracture nonunion)の治療経験

    山川 泰明, 野田 知之, 井上 円加, 金澤 智子, 長谷井 嬢, 斎藤 太一, 中原 龍一, 島村 安則, 尾崎 敏文

    中国・四国整形外科学会雑誌   26 ( 1 )   155 - 155   2014年4月

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    記述言語:日本語   出版者・発行元:中国・四国整形外科学会  

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  • 骨肉腫患者治療後の長期的問題点

    武田 健, 国定 俊之, 長谷井 嬢, 上原 健敬, 大森 敏規, 尾崎 敏文

    日本整形外科学会雑誌   88 ( 2 )   S131 - S131   2014年3月

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    記述言語:日本語   出版者・発行元:(公社)日本整形外科学会  

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  • Favorable outcome after complete resection in elderly soft tissue sarcoma patients: Japanese Musculoskeletal Oncology Group study 査読

    Y. Yoneda, T. Kunisada, N. Naka, Y. Nishida, A. Kawai, T. Morii, K. Takeda, J. Hasei, Y. Yamakawa, T. Ozaki

    EJSO   40 ( 1 )   49 - 54   2014年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.ejso.2013.09.004

    Web of Science

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  • 埋込型中心静脈カテーテルの断裂を来した2例

    上原 健敬, 武田 健, 兒島 聡一, 長谷井 嬢, 郷原 英夫, 国定 俊之, 尾崎 敏文

    中国・四国整形外科学会雑誌   25 ( 3 )   509 - 509   2013年10月

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    記述言語:日本語   出版者・発行元:中国・四国整形外科学会  

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  • 骨線維性異形成の治療成績

    武田 健, 国定 俊之, 上原 健敬, 大森 敏規, 長谷井 嬢, 尾崎 敏文

    中部日本整形外科災害外科学会雑誌   56 ( 秋季学会 )   56 - 56   2013年9月

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    記述言語:日本語   出版者・発行元:(一社)中部日本整形外科災害外科学会  

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  • 長期生存が得られた胸椎原発Ewing肉腫の2例

    上原 健敬, 国定 俊之, 武田 健, 長谷井 嬢, 田中 雅人, 尾崎 敏文

    日本整形外科学会雑誌   87 ( 6 )   S1170 - S1170   2013年6月

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    記述言語:日本語   出版者・発行元:(公社)日本整形外科学会  

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  • 上腕三頭筋切除を要した軟部肉腫の術後患肢機能

    武田 健, 国定 俊之, 長谷井 嬢, 井上 円加, 大森 敏規, 上原 健敬, 山川 泰明, 尾崎 修平, 吉田 晶, 尾崎 敏文

    日本整形外科学会雑誌   87 ( 6 )   S1190 - S1190   2013年6月

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    記述言語:日本語   出版者・発行元:(公社)日本整形外科学会  

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  • 骨盤骨腫瘍

    武田 健, 上原 健敬, 大森 敏規, 原田 遼三, 長谷井 嬢, 吉田 晶, 尾崎 敏文, 国定 俊之

    中国・四国整形外科学会雑誌   25 ( 1 )   239 - 239   2013年4月

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    記述言語:日本語   出版者・発行元:中国・四国整形外科学会  

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  • Dual Programmed Cell Death Pathways Induced by p53 Transactivation Overcome Resistance to Oncolytic Adenovirus in Human Osteosarcoma Cells 査読 国際誌

    Joe Hasei, Tsuyoshi Sasaki, Hiroshi Tazawa, Shuhei Osaki, Yasuaki Yamakawa, Toshiyuki Kunisada, Aki Yoshida, Yuuri Hashimoto, Teppei Onishi, Futoshi Uno, Shunsuke Kagawa, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara

    Molecular Cancer Therapeutics   12 ( 3 )   314 - 325   2013年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1158/1535-7163.MCT-12-0869

    Web of Science

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  • A simple detection system for adenovirus receptor expression using a telomerase-specific replication-competent adenovirus 国際誌

    T. Sasaki, H. Tazawa, J. Hasei, S. Osaki, T. Kunisada, A. Yoshida, Y. Hashimoto, S. Yano, R. Yoshida, S. Kagawa, F. Uno, Y. Urata, T. Ozaki, T. Fujiwara

    GENE THERAPY   20 ( 1 )   112 - 118   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/gt.2011.213

    Web of Science

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  • 大腿骨遠位骨幹部骨折偽関節の治療経験

    山川 泰明, 野田 知之, 井上 円加, 金澤 智子, 長谷井 嬢, 斎藤 太一, 中原 龍一, 島村 安則, 尾崎 敏文, 木浪 陽, 皆川 寛, 高城 康師, 川上 和秀

    中国・四国整形外科学会雑誌   24 ( 3 )   503 - 503   2012年10月

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    記述言語:日本語   出版者・発行元:中国・四国整形外科学会  

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  • 後内側剪断骨片を有する脛骨近位部関節内骨折に対する固定方法の検討

    小澤 正嗣, 野田 知之, 山川 泰明, 金澤 智子, 長谷井 嬢, 齋藤 太一, 中原 龍一, 木浪 陽, 島村 安則, 国定 俊之, 尾崎 敏文

    骨折   34 ( Suppl. )   S170 - S170   2012年6月

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    記述言語:日本語   出版者・発行元:(一社)日本骨折治療学会  

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  • 関節内骨折の克服 治療成績の向上を目指して 関節内骨折の克服 治療成績の向上を目指して 足関節内骨折

    野田 知之, 島村 安則, 中原 龍一, 齋藤 太一, 金澤 智子, 長谷井 嬢, 井上 円加, 山川 泰明, 国定 俊之, 尾崎 敏文, 木浪 陽

    骨折   34 ( Suppl. )   S9 - S9   2012年6月

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    記述言語:日本語   出版者・発行元:(一社)日本骨折治療学会  

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  • 下肢長管骨関節近傍骨折に対する一時的創外固定の有用性

    野田 知之, 島村 安則, 西山 武, 中原 龍一, 雑賀 建多, 斉藤 太一, 金澤 智子, 長谷井 嬢, 尾崎 敏文

    日本創外固定・骨延長学会雑誌   23   207 - 207   2012年1月

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    記述言語:日本語   出版者・発行元:日本創外固定・骨延長学会  

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  • 脛骨近位部関節内骨折の関節面骨折形態のCTによる評価

    小澤 正嗣, 野田 知之, 金澤 智子, 長谷井 嬢, 齋藤 太一, 中原 龍一, 島村 安則, 国定 俊之, 尾崎 敏文

    骨折   33 ( Suppl. )   S212 - S212   2011年7月

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    記述言語:日本語   出版者・発行元:(一社)日本骨折治療学会  

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  • Preclinical evaluation of telomerase-specific oncolytic virotherapy for human bone and soft tissue sarcomas. 国際誌

    Tsuyoshi Sasaki, Hiroshi Tazawa, Jo Hasei, Toshiyuki Kunisada, Aki Yoshida, Yuuri Hashimoto, Shuya Yano, Ryosuke Yoshida, Futoshi Uno, Shunsuke Kagawa, Yuki Morimoto, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara

    Clinical cancer research : an official journal of the American Association for Cancer Research   17 ( 7 )   1828 - 38   2011年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: Tumor-specific replication-selective oncolytic virotherapy is a promising antitumor therapy for induction of cell death in tumor cells but not of normal cells. We previously developed an oncolytic adenovirus, OBP-301, that kills human epithelial malignant cells in a telomerase-dependent manner. Recent evidence suggests that nonepithelial malignant cells, which have low telomerase activity, maintain telomere length through alternative lengthening of telomeres (ALT). However, it remains unclear whether OBP-301 is cytopathic for nonepithelial malignant cells. Here, we evaluated the antitumor effect of OBP-301 on human bone and soft tissue sarcoma cells. EXPERIMENTAL DESIGN: The cytopathic activity of OBP-301, coxsackie and adenovirus receptor (CAR) expression, and telomerase activity were examined in 10 bone (OST, U2OS, HOS, HuO9, MNNG/HOS, SaOS-2, NOS-2, NOS-10, NDCS-1, and OUMS-27) and in 4 soft tissue (CCS, NMS-2, SYO-1, and NMFH-1) sarcoma cell lines. OBP-301 antitumor effects were assessed using orthotopic tumor xenograft models. The fiber-modified OBP-301 (termed OBP-405) was used to confirm an antitumor effect on OBP-301-resistant sarcomas. RESULTS: OBP-301 was cytopathic for 12 sarcoma cell lines but not for the non-CAR-expressing OUMS-27 and NMFH-1 cells. Sensitivity to OBP-301 was dependent on CAR expression and not on telomerase activity. ALT-type sarcomas were also sensitive to OBP-301 because of upregulation of human telomerase reverse transcriptase (hTERT) mRNA following virus infection. Intratumoral injection of OBP-301 significantly suppressed the growth of OST and SYO-1 tumors. Furthermore, fiber-modified OBP-405 showed antitumor effects on OBP-301-resistant OUMS-27 and NMFH-1 cells. CONCLUSIONS: A telomerase-specific oncolytic adenovirus is a promising antitumor reagent for the treatment of bone and soft tissue sarcomas.

    DOI: 10.1158/1078-0432.CCR-10-2066

    PubMed

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  • Centpillar stemで著明なゆるみを生じた1例

    長谷井 嬢, 遠藤 裕介, 鉄永 智紀, 藤原 一夫, 三谷 茂, 尾崎 敏文

    日本人工関節学会誌   40   724 - 725   2010年12月

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    記述言語:日本語   出版者・発行元:(一社)日本人工関節学会  

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  • 鎖骨骨幹部骨折に対するMIPOによる治療経験

    島村 安則, 野田 知之, 中原 龍一, 斎藤 太一, 金澤 智子, 長谷井 嬢, 雑賀 建多, 井上 円加, 尾崎 敏文

    骨折   32 ( Suppl. )   S82 - S82   2010年7月

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    記述言語:日本語   出版者・発行元:(一社)日本骨折治療学会  

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▼全件表示

書籍等出版物

  • 肉腫 : 基礎・臨床の最新知見

    日本臨牀社

    日本臨牀社  2020年10月 

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    総ページ数:vii, 692, 11p   記述言語:日本語

    CiNii Books

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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

    田口, 智章, 黒田, 達夫

    メジカルビュー社  2017年8月  ( ISBN:9784758304658

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    総ページ数:313p   記述言語:日本語

    CiNii Books

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  • 小児整形外科テキスト

    日本小児整形外科学会教育研修委員会, 日本小児整形外科学会

    メジカルビュー社  2016年12月  ( ISBN:9784758313742

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    総ページ数:381p   記述言語:日本語

    CiNii Books

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  • 初期研修医・後期研修医のための必修整形外科

    尾崎, 敏文, メジカルビュー社

    メジカルビュー社  2016年10月 

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    総ページ数:235p   記述言語:日本語

    CiNii Books

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  • 分子細胞治療フロンティア2015

    外科分子細胞治療研究会

    飯田橋パピルス,パピルス (販売)  2014年8月  ( ISBN:9784990253141

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    総ページ数:236p   記述言語:日本語

    CiNii Books

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MISC

▼全件表示

講演・口頭発表等

  • 薬事承認を目指した骨肉腫X線画像読影AIの開発 招待

    長谷井嬢, 中原龍一, 藤原智洋, 中田英二, 国定俊之, 尾崎敏

    第58回日本整形外科学会骨・軟部腫瘍学術集会  2025年7月18日 

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    開催年月日: 2025年7月17日 - 2025年7月18日

    会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • 骨・軟部腫瘍診療におけるデジタルトランスフォーメーション 招待

    長谷井嬢, 中原龍一, 藤原智洋, 中田英二, 国定俊之, 尾崎敏

    第58回日本整形外科学会骨・軟部腫瘍学術集会  2025年7月17日 

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    開催年月日: 2025年7月17日 - 2025年7月18日

    会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • 希少疾患に対するAI開発戦略 招待

    長谷井嬢, 中原龍一, 藤原智洋, 中田英二, 国定俊之, 尾崎敏文

    第38回日本整形外科学会基礎学術集会  2023年10月20日 

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    開催年月日: 2023年10月19日 - 2023年10月20日

    会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • AIを用いた骨肉腫X線読影における転移学習の効果 招待

    長谷井嬢, 中原龍一, 藤原智洋, 中田英二, 国定俊之, 尾崎敏文

    第96回 日本整形外科学会学術総会  2023年5月13日 

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    開催年月日: 2023年5月11日 - 2023年5月14日

    会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • 希少疾患を対象としたAI開発における転移学習の有効性 招待

    長谷井 嬢

    第17回 日本CAOS研究会  2023年3月2日 

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    開催年月日: 2023年3月2日 - 2023年3月3日

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  • 孤独から繋がりへ - メタバースが実現する希少がん患者同士の出会い 招待

    長谷井 嬢

    高知大学医学部「医療×VR」学講座・東京大学大学院医学系研究科デジタルメンタルヘルス講座 第3回合同シンポジウム  2025年2月15日 

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    会議種別:公開講演,セミナー,チュートリアル,講習,講義等  

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  • デジタル技術で診療を考えてみる ~現場から始まるイノベーション~ 招待

    長谷井 嬢

    第30回岡山大学外科MCセミナー  2025年2月8日 

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    会議種別:公開講演,セミナー,チュートリアル,講習,講義等  

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  • 生成AIがもたらす医療変革 招待

    長谷井 嬢

    国立大学病院臨床研究推進会議 第13回総会シンポジウムプログラム  2025年1月27日 

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    会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • AIとメタバースを用いた骨軟部腫瘍診療革命-早期診断から患者支援まで- 招待

    長谷井嬢

    第62回日本癌治療学会学術集会  2024年10月26日 

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    会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • 生成AIを使って 小児股関節診療を考えてみる 招待

    長谷井嬢, 藤原智洋, 中田英二, 国定俊之, 尾崎敏

    第63回日本小児股関節研究会  2024年6月7日 

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  • 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

    第97回 日本整形外科学会学術総会  2024年5月26日 

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    会議種別:ポスター発表  

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  • 希少がん患者の孤独感を改善する~メタバースを用いた挑戦~ 招待

    長谷井嬢

    第15回日本臨床試験学会  2024年3月2日 

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  • 骨腫瘍X線読影AIの開発と、医療におけるデジタルツインの可能性 招待

    長谷井 嬢

    第16回四国骨軟部腫瘍研究会  2023年3月18日 

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  • あまり知らない(知りたくもない?)骨軟部腫瘍の世界と医療のDX化 招待

    長谷井 嬢

    水島中央病院 整形外科院内講演会  2022年11月30日 

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  • 人工知能による骨肉腫X線読影システムの開発と骨端線認識への挑戦

    長谷井嬢, 中原龍一, 国定俊之, 中澤慎二, 韓, 藏品, 木浪, 藤原一夫, 臼井正明, 尾崎敏

    第55回 日本整形外科学会 骨・軟部腫瘍学術集会  2022年7月15日 

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  • AIによる骨肉腫X線読影システムの偽陽性対策

    長谷井嬢, 中原龍一, 藤原智洋, 中田英二, 国定俊之, 木浪 陽, 藤原一夫, 臼井正明, 尾崎敏文

    第37回 日本整形外科学会基礎学術集会  2022年 

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    会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • 骨・軟部腫瘍診療におけるAI診断の現状と未来

    長谷井嬢, 中原龍一, 国定俊之, 中澤慎二, 韓 昌煕, 藏品 豊, 木浪 陽, 藤原一夫, 臼井正明

    第95回日本整形外科学会学術総会  2022年 

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    会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • AIの変遷と、腫瘍を含めた股関節周囲疾患における開発動向 招待

    長谷井 嬢

    第48回日本股関節学会学術集会  2021年 

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    会議種別:公開講演,セミナー,チュートリアル,講習,講義等  

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  • 下腿近位部悪性骨軟部腫瘍広範切除後における腓腹筋皮弁の成績

    長谷井嬢, 中田英二, 国定俊之, 尾崎敏文

    第132回 中部日本整形外科災害外科学会・学術集会  2019年 

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    会議種別:シンポジウム・ワークショップ パネル(公募)  

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  • Augmentation of Anti PD-1 Antibody Immunotherapy With Telomerase-Specific Oncolytic Virotherapy in Osteosarcoma 招待

    2nd International Combined Meeting of Orthopaedic Research Societies  2019年 

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    会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • TWIST1はヒト軟骨細胞において、DNAのヒドロキシメチル化によりMMP3発現を誘導し、軟骨異化を促進する

    長谷井 嬢

    第32回 日本軟骨代謝学会  2019年 

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    会議種別:公開講演,セミナー,チュートリアル,講習,講義等  

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  • 広範囲骨欠損症例に対するMasquelet法の有効性

    長谷井嬢, 野田知之, 島村安則, 中原龍一, 木浪陽, 井上円加, 皆川寛, 京英紀, 武富雅則, 尾﨑敏文

    第38回日本骨折治療学会  2012年 

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    会議種別:シンポジウム・ワークショップ パネル(公募)  

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受賞

  • 第61回 山陽放送学術文化・スポーツ振興財団学術奨励賞

    2024年6月   山陽放送学術文化・スポーツ振興財団   メタバースを用いた小児・AYA世代希少がん患者の孤独からの救済

    長谷井嬢, 石田 悠志, 片山 英樹

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  • 岡山大学病院長賞「楷の木賞」

    2024年1月   岡山大学病院   岡山大学病院3Dマップ作成について

    長谷井嬢

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  • 岡山大学ピッチコンテスト2023 中国銀行賞

    2023年9月   岡山大学   骨軟部診療における医師間相談アプリ

    長谷井 嬢

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  • 第14回日本CAOS研究会 web 奨励賞

    2020年9月   第14回日本CAOS研究会   骨肉腫X線画像の読影を目指した人工知能の開発

    長谷井 嬢

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  • 第133回 中部整形外科学会 学会奨励賞

    2019年   第133回 中部整形外科学会   次世代シークエンサーを用いた変形性膝関節症発症メカニズムの解明

    長谷井 嬢

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  • 第32回 日本軟骨代謝学会 学会奨励賞

    2019年   第32回 日本軟骨代謝学会   TWIST1はヒト軟骨細胞において、DNAのヒドロキシメチル化によりMMP3発現を誘導し、軟骨異化を促進する

    長谷井 嬢

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  • 桃整会学術奨励賞

    2018年   岡山大学整形外科   TWIST1 induces MMP3 expression through up-regulating DNA hydroxymethylation and promotes catabolic responses in human chondrocytes

    長谷井 嬢

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  • 第51回 日本整形外科学会 骨・軟部腫瘍学術集会 優秀ポスター賞

    2018年   第51回 日本整形外科学会 骨・軟部腫瘍学術集会   骨肉腫におけるABCトランスポーター遺伝子発現と点塩基変異解析による予後予測

    長谷井 嬢

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  • 研究助成アルケア奨励賞

    2018年   公益財団法人 整形災害外科学研究助成財団  

    長谷井 嬢

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  • がん研究奨励賞(林原賞・山田賞)

    2014年   岡山医学会   p53の転写活性化によって誘導される2種類のプログラム細胞死の誘導機構はヒト骨肉腫細胞における腫瘍融解アデノウイルスへの耐性を克服する

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  • 第46回 日本整形外科学会 骨・軟部腫瘍学術集会 優秀ポスター賞

    2013年   第46回 日本整形外科学会 骨・軟部腫瘍学術集会   p53武装化腫瘍融解アデノウイルスはOBP-301抵抗性骨肉腫細胞株にmicroRNAを介し高率にアポトーシスを誘導する

    長谷井 嬢

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共同研究・競争的資金等の研究

  • 骨軟部腫瘍特化型の対話型AIアプリを利用した骨軟部腫瘍診療相談システムの開発

    研究課題/領域番号:JPMJSF23BB  2023年10月 - 2025年03月

    国立研究開発法人科学技術振興機構(JST)  大学発新産業創出基金事業 可能性検証 

    長谷井 嬢

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    担当区分:研究代表者 

    骨軟部腫瘍特化型の専門医への相談機能を搭載するチャットボットを開発する。医師間で使用するアプリとして、開発後はビジネスモデルを確立し、起業の可能性を検証する。将来的には全診療科の希少疾患に対象疾患を広げ、希少疾患情報と診療医を繋いで相談できるマッチングサービスアプリへと発展するその基盤構築を行う。

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  • 患者体験の最適化と医療技術の進化を目指した医療DX開発

    2023年10月 - 2024年03月

    岡山大学  岡山大学 次世代研究育成グループ事業 

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  • デジタルツインを用いた患者案内と、メタバースを用いたジェンダー患者相談システムの開発

    2023年04月 - 2025年03月

    公益財団法人 橋本財団  福祉助成金 

    長谷井 嬢、松本 洋輔

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  • AIによるCT画像を用いたサルコペニアリスク完全自動解析

    2023年04月 - 2024年03月

    国立研究開発法人日本医療研究開発機構(AMED)  橋渡し研究プログラム シーズA 2022年 

    長谷井 嬢、濱田 全紀、 堅山 佳美、 難波 孝礼

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    担当区分:研究代表者 

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  • AIによる骨腫瘍X線画像読影システムの開発と臨床研究

    研究課題/領域番号:22579674  2022年04月 - 2027年03月

    国立研究開発法人日本医療研究開発機構(AMED)  日本医療研究開発機構研究費 

    尾崎敏文, 長谷井嬢, 中原龍一, 大塚 裕次朗

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    担当区分:研究分担者 

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  • AIによる原発性悪性骨腫瘍X線画像読影システムの開発

    2022年

    国立研究開発法人日本医療研究開発機構(AMED)  橋渡し研究プログラム シーズA 

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  • 人工知能による物体検出を用いた原発性悪性骨腫瘍X線読影システムの開発と臨床応用

    研究課題/領域番号:21K09228  2021年04月 - 2024年03月

    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)

    長谷井 嬢, 中原 龍一, 尾崎 敏文

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    今回の研究では、臨床応用まで見据えた計画としたいため、研究目標として薬事承認を目指すこととした。そのために必要な、国内臨床試験(性能試験)を予定することとなった。そのため、研究をプログラム開発のための探索フェーズと、臨床試験フェーズ(薬事申請提出用データ)に分けて設定することとした。そのため、倫理委員会の申請も分けて行うこととし、岡山大学内にある新医療開発センターへ相談し、倫理委員会の申請から分けて行うことした。新規の倫理委員会申請書類を作成し、新医療開発センターによる書類のレビューを行い申請を行った。また、データ提供いただいている研究協力施設(近畿大学病院、弘前大学附属病院、金沢大学付属病院、大阪国際医療センター、水島中央病院)へも新規に倫理委員会申請となることを説明し了解を得て、これまでの研究については一旦終了扱いとして、新規に当院の認定倫理委員会で一括審査を行っている。また、臨床使用を目指すため、画像データはこれまでの研究ではPNGデータで開発を行ってきたが、DICOMそのもののデータを匿名化したもので再度開発を開始する体制を構築した。匿名化のステータス確認のために、新医療開発センター内において匿名化に問題がないことを確認後、データをクラウドに移行して研究を行うこととしている。また、薬事申請のために、PMDAへの事前相談を予定しており、新規研究計画が承認され次第、資料作成と相談を行う予定である。

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  • 肉腫における体液分子診断技術の開発と標的分子による新たな腫瘍進展機序の解明

    研究課題/領域番号:19H03784  2019年04月 - 2022年03月

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

    尾崎 敏文, 藤原 智洋, 長谷井 嬢, 杉原 進介, 畑 利彰, 横尾 賢, 清野 正普

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    配分額:12870000円 ( 直接経費:9900000円 、 間接経費:2970000円 )

    本研究は、バイオマーカーに極めて乏しい肉腫に対し、近年確立されつつある体液診断技術の手法を検討することにより、最も有効な方法を確立することである。今年度は、骨肉腫細胞、粘液線維肉腫および滑膜肉腫細胞における腫瘍分泌エクソソームの抽出を行い、エクソソームの確認として、ゼータサイザーを用いた動的散乱光や電子顕微鏡(TEM)によるサイズの確認、またエクソソームマーカーであるテトラスパニン蛋白の確認をウエスタンブロット法を用いて行った。
    また、滑膜肉腫由来の分泌エクソソームおよび患者由来の血中エクソソームを抽出し、両者の膜表面タンパクをプロテオーム解析により特定した。さらに患者治療効果に沿った発現変動を追い、感度・特異度に優れた標的タンパクを特定した。
    上記で特定した肉腫由来循環エクソソームが腫瘍自身、腫瘍周囲微小環境、遠隔転移先で腫瘍進展に対しどのような影響を与えているか、in vitroモデルで評価した。骨肉腫転移に深く関わっている正常線維芽細胞・血管内皮細胞・肺微小血管内皮細胞・肺線維芽細胞を用い、in vitro環境下で腫瘍周囲および肺組織微小環境モデルを作成した。各転移能の異なる骨肉腫腫瘍細胞由来エクソソームを添加し、それぞれの細胞株の機能変化を解析した。

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  • ゲノムワイドエンハンサー解析を用いたTWIST1の変形性関節症寄与メカニズム解明

    研究課題/領域番号:18K09065  2018年04月 - 2022年03月

    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)

    長谷井 嬢, 寺村 岳士, 村川 泰裕

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    不死化ヒト軟骨細胞株(TC28)においてTWIST1を強制発現させ、LC-MSでTWIST1と結合するタンパク質を網羅的に測定した。また、TC28にAd-TWIST1-IRES-GFPを用いてTWIST1を高発現させたのち、FACS ariaでGFP発現のある細胞だけをソートし、TWIST1高発現細胞株を集めてRNA抽出を行った。このサンプルを分担施設である理研-HMC臨床オミックス特別ユニットへ送付し、共同研究の形で、CAGE法によりゲノムワイドにエンハンサー領域の検出を行った。この結果は既にデータとして受け取っており、現在は近畿大学と共同でCAGEデータの解析と、インフォマティクス解析によりTWIST1関連エンハンサー領域候補の解析を行っている。また並行して、TC28にMycタグを付加したTWIST1を強制発現したサンプルを用いて、Myc抗体でクロマチンIPを行い、バリデーション作業を行っている。また、確認の為には、2つのguideRNAを用いてCRISPR-deletionにより特異的にエンハンサーの除去を行い、転写に変化が起きるか観察する事が必要である。エンハンサーを抜き取る形でゲノム編集する必要があり、きれいに抜けた細胞のみを選択し解析する工程に多くの時間を要している。現在も実験を継続中である。

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  • NGSを用いたOA関連遺伝子の網羅的解析と、5-hmc変動が解き明かす病態機序

    研究課題/領域番号:16K20075  2016年04月 - 2018年03月

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    長谷井 嬢

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    配分額:3900000円 ( 直接経費:3000000円 、 間接経費:900000円 )

    次世代RNAシークエンスでTWIST1はヒトOA軟骨で高発現している事が示唆され、OA軟骨組織では正常軟骨組織と比較して約10倍にTWIST1が発現上昇していた。TWIST1をヒト軟骨細胞に過剰発現させることでMMP1, MMP3が発現上昇していた。ヒト不死化軟骨細胞株にTWIST1を過剰発現させると、MMP3プロモーターにおける5hmCステータス上昇が確認できた。TWIST1をTC28に恒常的に高発現させると、TET1発現が上昇し、TET triple KO fibroblastにTWIST1を発現誘導させると、TET triple KO 細胞ではMMP3の発現誘導が抑制された。

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  • microRNA-140 による軟骨保護作用の解析と標的遺伝子の解明

    2014年

    上原記念生命科学財団  ポストドクトラルフェローシップ 

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  • 患者の社会参画と医療者支援を両立する生成AIメンタルケアプラットフォームの開発

    2025年03月 - 2026年02月

    公益財団法人 橋本財団  福祉助成金 福祉機器等開発 

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    担当区分:研究代表者 

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  • メタバースで全国を繋ぐ-小児・AYA世代希少がん患者のメンタルヘルス向上を目指した新システムの開発-

    2024年10月 - 2025年09月

    公益財団法人三菱財団  社会福祉事業・研究助成 

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    担当区分:研究代表者 

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  • デジタル技術を介した小児・AYA世代がん患者への教育・メンタルの統合サポート開発

    2024年08月 - 2026年07月

    公益財団法人 日本生命財団  児童・少年の健全育成実践的研究助成 

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    担当区分:研究代表者 

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  • メタバースを用いた小児・AYA世代希少がん患者の孤独からの救済

    2024年06月 - 2025年05月

    山陽放送学術文化・スポーツ振興財団  山陽放送学術文化・スポーツ振興財団研究助成 

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    担当区分:研究代表者 

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  • AIカウンセラーを用いた小児・AYA世代がん患者のメンタルケア

    2024年04月 - 2025年03月

    公益財団法人ウエスコ学術振興財団  研究活動費助成事業 

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    担当区分:研究代表者 

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  • 肉腫治療による長期入院患者のメンタルケアを目指したメタバース活用

    2023年10月 - 2024年09月

    公益財団法人 がんの子どもを守る会  がんの子どもを守る会研究助成 

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    担当区分:研究代表者 

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  • 医療情報化診療支援技術開発講座開設

    2022年 - 2024年

    経済産業省  高等教育機関における共同講座創造支援事業費補助金 

    長谷井 嬢, 大塚 裕次朗、中村 優介

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    担当区分:研究代表者 

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  • 岡山大学病院外来空間のバーチャル化と、メタバース空間によるアバターを用いたジェンダー相談システム

    2022年 - 2023年03月

    岡山大学  Society5.0研究支援プログラム 

    長谷井 嬢, 松本 洋輔

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    担当区分:研究代表者 

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  • CT画像を用いた完全自動サルコペニア診断システムの開発, 病院間骨軟部腫瘍相談アプリの開発, 岡山大学病院外来空間のデジタルツイン作成と、メタバースを用いたジェンダー相談空間の設置.

    2022年 - 2023年03月

    岡山大学  岡山大学 次世代研究育成グループ事業 

    長谷井 嬢

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    担当区分:研究代表者 

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  • Deep learningを用いた原発性悪性骨腫瘍の画像診断技術の開発

    2020年

    特定非営利活動法人 ゴールドリボン  ゴールドリボン研究助成 

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  • 複合現実技術を用いた次世代骨盤手術支援ツールの開発

    2019年

    公益財団法人ウエスコ学術振興財団  ウエスコ学術振興財団研究助成 

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  • TWIST1が5-ヒドロキシメチルシトシンを介して制御する変形性膝関節症の病態解析

    2018年

    公益財団法人 中冨健康科学振興財団  中冨健康科学振興財団研究助成 

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    日本学術振興会  科学研究費助成事業 挑戦的萌芽研究  挑戦的萌芽研究

    尾崎 敏文, 榮川 伸吾, 長谷井 嬢, 上原 健敬, 鵜殿 平一郎, 藤原 智洋

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    配分額:3380000円 ( 直接経費:2600000円 、 間接経費:780000円 )

    本研究ではマウス骨肉腫モデルにおいて,CD11b陽性の免疫細胞主体の抗腫瘍免疫機構の存在が明らかとなった.また,CD8TILs, Tregと同様に骨髄球系細胞においてもメトホルミンが細胞内代謝を制御することで抗腫瘍効果を惹起することが示され,それは細胞内における嫌気的解糖の促進によるものであった.先行研究と合わせると腫瘍微小環境においてメトホルミンがT cells, CD11b陽性細胞の双方で同様に嫌気的解糖を促進しており,腫瘍微小環境におけるglucoseの代謝制御が抗腫瘍免疫と密接に関連していることが示唆された.

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  • ABCトランスポーターに着目した、骨肉腫新規治療戦略と予後予測因子としての有益性の検討

    2015年

    公益財団法人 がんの子どもを守る会  がんの子どもを守る会研究助成 

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  • microRNAによる軟骨保護作用の解析と標的遺伝子の解明

    2012年03月 - 2013年02月

    リウマチ財団  リウマチ疾患研究助成 

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