Updated on 2025/08/21

写真a

 
Mochizuki Yusuke
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Special-Appointment Assistant Professor
Position
Special-Appointment Assistant Professor
External link
 

Papers

  • 脛骨高原骨折の治療戦略 脛骨近位端骨折に対するプレート固定 単顆骨折および両顆骨折に対する使用の基本と応用

    依光 正則, 望月 雄介, 長谷川 翼, 奥田 龍一郎, 安藤 輝彦, 尾崎 敏文

    中部日本整形外科災害外科学会雑誌   68 ( 秋季学会 )   59 - 59   2024.10

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    Language:Japanese   Publisher:(一社)中部日本整形外科災害外科学会  

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  • p53-armed oncolytic virotherapy induces abscopal effect in osteosarcoma by promoting immunogenic cell death. Reviewed International journal

    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   2024.9

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

    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   2024.4

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    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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  • Five cases of atypical ulnar fractures associated with long-term bisphosphonate use: An anatomical and mechanical analysis using a finite element model

    Shunji Okita, Taichi Saito, Norio Yamamoto, Yusuke Mochizuki, Ryuichi Nakahara, Yasunori Shimamura, Toshiyuki Kunisada, Keiichiro Nishida, Toshifumi Ozaki

    Journal of Orthopaedic Science   2022.11

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.jos.2022.09.017

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  • Effectiveness of Cement Augmentation on Early Postoperative Mobility in Patients Treated for Trochanteric Fractures with Cephalomedullary Nailing: A Prospective Cohort Study. Reviewed International journal

    Yusuke Mochizuki, Norio Yamamoto, Tatsuya Fujii, Yosuke Tomita

    Journal of personalized medicine   12 ( 9 )   2022.8

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    Fixation using cephalomedullary nails (CMNs) with additional cement augmentation (CA) was developed as a novel treatment option for the osteosynthesis of osteoporotic trochanteric fractures, though the effectiveness of CA on early postoperative mobility remains uncertain. This multicenter prospective cohort study aimed to estimate the effectiveness of CA on early postoperative mobility in patients with trochanteric fractures. We enrolled patients with femoral trochanteric fractures aged >60 years who were able to walk independently before the injury. The primary outcome was the postoperative 3-day cumulated ambulation score (CAS); the secondary outcome was the visual analog scale (VAS) pain score at rest and during movement on postoperative days 1−3. The outcomes of the patients treated using CMNs with or without CA were compared. Sixty-three eligible patients were categorized into CA (n = 32) and control (n = 31) groups. In univariate analysis, the CA group had significantly higher CAS values, lower VAS scores at rest on day 1 postoperatively, and lower VAS scores during movement on day 3. In multivariable linear regression analyses, the CA group had significantly higher CAS values (beta, 2.1; 95% confidence interval, 0.5 to 3.6; p = 0.01). The CA group had a negative adjusted beta value in their VAS scores during movement. This study indicated that CA was associated with a high CAS value in patients with geriatric trochanteric fractures. However, CA was not associated with pain reduction at rest and during movement during the initial postoperative days.

    DOI: 10.3390/jpm12091392

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  • Hip Fractures after Intramedullary Nailing Fixation for Atypical Femoral Fractures: Three Cases.

    Norio Yamamoto, Tomoo Inoue, Yusuke Mochizuki, Tomoyuki Noda, Keisuke Kawasaki, Toshifumi Ozaki

    Acta medica Okayama   76 ( 3 )   317 - 321   2022.6

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    Secondary hip fractures (SHFs) rarely occur after intramedullary nailing (IMN) fixation without femoral neck fixation for atypical femoral fractures (AFFs). We report three cases of older Japanese women who sustained SHFs presumably caused by osteoporosis and peri-implant stress concentration around the femoral neck after undergoing IMN without femoral neck fixation for AFF. All cases were fixed with malalignment. In AFF patients, postoperative changes due to postoperative femoral bone malalignment may affect the peri-implant mechanical environment around the femoral neck, which can result in insufficiency fractures. At the first AFF surgery, we recommend femoral neck fixation after adequate reduction is achieved.

    DOI: 10.18926/AMO/63741

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  • Application of mesh plate for the treatment of an osteochondral fracture of the medial femoral condyle with medial wall fracture: A case report. International journal

    Yusuke Mochizuki, Norio Yamamoto, Tomoyuki Noda, Toshifumi Ozaki

    Acta orthopaedica et traumatologica turcica   56 ( 3 )   228 - 231   2022.5

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    Osteochondral fractures of the medial femoral condyle accompanied by medial wall fracture are rare. Surgeons often have difficulty in selecting the most appropriate treatment, especially the plating technique for internal fixation since the available femoral locking plates are made to fit the femoral lateral condyle and there is no anatomical plate for the medial condyle. We, herein, report a case of a 44-year- old female patient who suffered from an osteochondral fracture of the medial femoral condyle accompanied by medial wall fracture treated by a low-profile mesh plate contoured to fit around the fracture site. Bone union was achieved at postoperative week 12 and the patient was able to return to her normal activities. At the 16-month follow-up exam, the patient's functional and clinical outcomes were satisfactory. Her Oxford knee score was 47 points, and the Western Ontario and McMaster Universities Arthritis Index scores were 2 points for pain and 5 points for physical function. We believe that the mesh plate has several advantages. This is the first report of using a mesh plate for the femur, and we were able to achieve good results. We conclude that treatment with a mesh plate can be applied in well- selected patients with medial femoral condyle osteochondral fracture and has the potential to be applied to the treatment of fractures in various regions in the future.

    DOI: 10.5152/j.aott.2022.21325

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  • Oncolytic virotherapy reverses chemoresistance in osteosarcoma by suppressing MDR1 expression. Reviewed International journal

    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   2021.9

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    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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  • Reduction quality and nail fixation ratio as bone-implant stability factors associated with reoperation for trochanteric fractures. Reviewed International journal

    Norio Yamamoto, Yosuke Tomita, Tomoyuki Noda, Tomoo Inoue, Yusuke Mochizuki, Toshifumi Ozaki

    Injury   52 ( 7 )   1813 - 1818   2021.7

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    INTRODUCTION: Geriatric trochanteric fractures are a major global issue, and their incidence is steadily rising. Bone quality, fracture type, fracture reduction quality, implant selection, and implant placement affect bone-implant stability in osteoporotic fractures. Our aim in this study was to evaluate the association between bone-implant stability factors, including nail construct, and the rate of reoperation in a more extensive case series with comprehensive variables. METHODS: This was a retrospective cohort study of 390 patients with trochanteric fractures aged ≥60 years and treated with intramedullary nailing. The primary outcome was the rate of reoperation due to any cause. Univariate and multivariable logistic regression analyses were used to identify factors associated with reoperation. RESULTS: In this study, 15 patients (3.8%) required reoperation. Univariate analysis showed that the following variables were significantly different between patients who required reoperation and those who did not: T-score at the total hip and lumbar spine, cortical thickness index, fracture type, and reduction quality. Multivariable logistic regression analysis showed that the odds ratio (OR) for A3 fracture type was 2.76 (95% confidence interval [CI], 0.77-9.76; p=0.116) and that for inadequate reduction, assessed by computed tomography, was 2.94 (95% CI, 0.89-9.69; p=0.076). These were independent predictors of reoperation. There was only one case (6.7%) of reoperation among patients with a distal femoral fragment fixation ratio (FR) >0.8. Considering the intraoperative decision-making process, the combination of inadequate reduction and an FR ≤0.8 were associated with the highest reoperation at a rate of 9.3% (OR, 3.327; 95% CI, 1.091-10.142; p=0.043). CONCLUSIONS: Risk factors on bone-implant stability for reoperation were the reduction quality and fracture type. Regarding the intraoperative decision-making process, the selection of a nail length with an FR >0.8 is a better option when the intramedullary reduction has been maintained intraoperatively.

    DOI: 10.1016/j.injury.2021.04.048

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  • Telomerase-specific oncolytic immunotherapy for promoting efficacy of PD-1 blockade in osteosarcoma. Reviewed International journal

    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   2021.5

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    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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  • Clinical outcomes of treatment with locking compression plates for distal femoral fractures in a retrospective cohort. Reviewed International journal

    Masahiro Kiyono, Tomoyuki Noda, Hiroshi Nagano, Takashi Maehara, Yasuaki Yamakawa, Yusuke Mochizuki, Takahiko Uchino, Suguru Yokoo, Koji Demiya, Kenta Saiga, Yasunori Shimamura, Toshifumi Ozaki

    Journal of orthopaedic surgery and research   14 ( 1 )   384 - 384   2019.11

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    BACKGROUND: Plate fixation is one of the standard surgical treatments for distal femoral fractures. There are few reports on the relationship between the screw position and bone union when fixing by the bridging plate (relative stability) method. METHODS: This retrospective study included 71 distal femoral fractures of 70 patients who were treated with the locking compression plate for distal femur (DePuy Synthes Co., Ltd, New Brunswick, CA, USA). The following measurements were evaluated and analyzed: (1) bone union rate, (2) bridge span length (distance between screws across the fracture), (3) plate span ratio (plate length/bone fracture length), (4) number of empty holes (number of screw holes not inserted around the fracture), and (5) medial fracture distance (bone fracture distance on the medial side of the distal femur). Patient demographics (age), comorbidities (smoking, diabetes, chronic steroid use, dialysis), and injury characteristics (AO type, open fracture, infection) were obtained for all participants. Univariate analysis was performed on them. RESULTS: Of 71 fractures, 26 fractures were simple fractures, 45 fractures were comminuted fractures, and 7 fractures resulted in non-union. Non-union rate was significantly higher in comminuted fractures with bone medial fracture distance exceeding 5 mm. Non-union was founded in simple fractures with bone medial fracture distance exceeding 2 mm, but not significant (p = 0.06). In cases with simple fractures, one non-union case had one empty hole and one non-union case had four empty holes, whereas in cases with comminuted fractures, five non-union cases had two more empty holes. CONCLUSIONS: We concluded that bone fragment distance between fracture fragments is more important than bridge span length of the fracture site and the number of empty holes. Smoking and medial fracture distance are prognostic risk factors of nonunion in distal femoral fractures treated with LCP as bridging plate.

    DOI: 10.1186/s13018-019-1401-9

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

    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   2019.3

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    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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  • Posterior buttress plate with locking compression plate for Hoffa fracture. Reviewed

    Tomonori Tetsunaga, Toru Sato, Naofumi Shiota, Masahiro Yoshida, Yusuke Mochizuki, Tomoko Tetsunaga, Arubi Teramoto, Yoshiki Okazaki, Kazuki Yamada

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association   18 ( 5 )   798 - 802   2013.9

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    BACKGROUND: Many difficulties are associated with treating fractures of the posterior condyle of the femur (Hoffa fractures). Anatomical reduction and internal fixation are optimum for such intra-articular fractures. Some surgeons use anteroposterior screws to achieve direct stability. However, screw fixation is not adequate in some cases. To increase stability, we treat Hoffa fractures with a posterior buttress plate; we use a twisted, 1/3 tubular plate at the posterior surface and a supplementary, locking compression plate (LCP) for additional stability. METHODS: Patients who had sustained Hoffa fractures between January 2006 and March 2009 were included in this study. Patients comprised three males and two females with a mean age of 73.6 years at the time of surgery. A 3.5-mm 1/3 tubular plate was twisted and applied to the posterolateral aspect of the distal femur. This was combined with an LCP on the distal femur to achieve a rafting effect. RESULTS: All fractures were healed within 15 weeks. There were no instances of nonunion, infection, or implant removal. The mean range of motion was -3° to 121°. Four patients had no pain in the treated limb and one had mild pain on weight bearing. The average Oxford Knee Score was 44.6 points. All patients achieved satisfactory joint function and regained their walking ability with good clinical results. CONCLUSIONS: Improved stability associated with this technique enables patients to begin range-of-motion training and return to their normal activities sooner; this resulted in good outcome.

    DOI: 10.1007/s00776-013-0410-5

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