Faculty Profiles - OZAKI Toshifumi

Papers - OZAKI Toshifumi

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Comparison of posterior root remnant cells and horn cells of the medial meniscus. International journal

Ximing Zhang, Takayuki Furumatsu, Yuki Okazaki, Takaaki Hiranaka, Haowei Xue, Keisuke Kintaka, Shinichi Miyazawa, Toshifumi Ozaki

Connective tissue research 1 - 10 2021.5

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

Purpose/Aim of the study: Previous studies have noted distinctions between medial meniscus posterior root and horn cells. However, the characteristics of root remnant cells have not been explored in detail. The purpose of this study was to evaluate the gene expression levels, proliferation, and resistance to mechanical stress of remnant and horn cells.Materials and Methods: Medial meniscus tissue samples were obtained from patients who underwent total or uni-compartmental knee arthroplasty. Cellular morphology, sry-type HMG box 9, type II collagen, and chondromodulin-I gene expression levels were analyzed. Collagen synthesis was assessed by immunofluorescence staining. Proliferation analysis after 4 h-cyclic tensile strain was performed.Results: Horn cells displayed triangular morphology, whereas root remnant cells appeared fibroblast-like. sry-type HMG box 9 mRNA expression levels were similar in both cells, but type II collagen and chondromodulin-I mRNA expressions were observed only in horn cells. The ratio of type II collagen-positive cells in horn cells was about 10-fold higher than that in root remnant cells, whereas the ratio of sry-type HMG box 9-positive cells was similar. A significant increase in proliferation was observed in root remnant cells compared to that in horn cells. Further, under cyclic tensile strain, the survival rate was higher in root remnant cells than in horn cells.Conclusions: Medial meniscus root remnant cells showed higher proliferation and resistant properties to cyclic tensile strain than horn cells and showed no chondromodulin-I expression. Preserving the medial meniscus posterior root remnant during pullout repair surgery might maintain mechanical stress-resistant tissue and support healing.

DOI： 10.1080/03008207.2021.1920935

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A retro-odontoid pseudotumor treated with fixation and tumor resection by the lateral approach: illustrative case. International journal

Yoshiaki Oda, Takamitsu Tokioka, Toshifumi Ozaki

Journal of neurosurgery. Case lessons 1 ( 19 ) CASE20160 2021.5

Language：English

BACKGROUND: A retro-odontoid pseudotumor is not a condition that requires resection. However, pathological diagnosis is required when a tumor such as a meningeal tumor or chordoma is suspected. The authors report a case of a large lesion treated with posterior fixation and tumor resection using a lateral approach. OBSERVATIONS: A 77-year-old man visited the authors' department complaining of neck pain and decreased dexterity of the upper extremities. Magnetic resonance imaging showed a large, beak-shaped lesion behind the dens and severe compression of the spinal cord. Surgery consisted of occipitocervical-C2 fixation, followed by tumor resection with a left lateral approach. The pathological diagnosis was consistent with a retro-odontoid pseudotumor. The tumor was resected to a relatively large extent and shrank over time, leading to complete disappearance. LESSONS: Pathological examination is also possible with a posterior approach if the tumor can be reached through the lateral edge of the dura. In that situation, the amount of resection is limited, and there is a risk of spinal cord compression. Intradural dissemination of tumors is a concern with the transdural approach. If tumor resection by the posterior approach is difficult, the lateral approach can facilitate tumor resection.

DOI： 10.3171/CASE20160

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Risk factors of postoperative delayed wound healing in patients with rheumatoid arthritis treated with a biological agent. International journal

Shunji Okita, Hajime Ishikawa, Asami Abe, Satoshi Ito, Kiyoshi Nakazono, Akira Murasawa, Keiichiro Nishida, Toshifumi Ozaki

Modern rheumatology 31 ( 3 ) 587 - 592 2021.5

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: This retrospective study aimed to investigate the risk factors associated with delayed wound healing (DWH) after orthopedic surgery in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: We reviewed medical records of 276 orthopedic procedures for 187 RA patients treated with bDMARDs. As a preoperative nutritional status assessment, we evaluated body mass index, prognostic nutritional index (PNI), and controlling nutritional status (CONUT). We evaluated DAS28-CRP, DAS28-ESR, face scale, global health, and HAQ-DI to assess the disease activity. Univariate and multivariate logistic regression analyses were performed to evaluate the risk factors for DWH. RESULTS: In 276 procedures, DWH was identified in 24 patients (8.7%). Disease duration, foot and ankle surgery, and preoperative use of tocilizumab were significant in the univariate analyses. These variables were entered into a multivariate model, and it was revealed that preoperative use of tocilizumab and procedures in the foot and ankle were associated with an increased risk of DWH. CONCLUSION: The current retrospective study suggested that preoperative use of tocilizumab and procedures in the foot and ankle were risk factors for DWH.

DOI： 10.1080/14397595.2020.1790138

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Telomerase-specific oncolytic immunotherapy for promoting efficacy of PD-1 blockade in osteosarcoma. 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

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

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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High body mass index is a risk factor for unfavorable clinical outcomes after medial meniscus posterior root repair in well-aligned knees.

Ximing Zhang, Takayuki Furumatsu, Yuki Okazaki, Takaaki Hiranaka, Yuya Kodama, Haowei Xue, Yoshiki Okazaki, Toshifumi Ozaki

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 26 ( 3 ) 430 - 434 2021.5

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Severe chondral lesions and varus knee alignment are associated with poor outcomes following transtibial pullout repair for medial meniscus posterior root tears and meniscus tear is strongly associated with body mass index. The prognostic factors in well-aligned knees (femorotibial angle < 180°) with mild chondral lesions are unknown. Therefore, we investigated the prognostic factors in these patients. We hypothesized that high body mass index would lead to poor clinical outcomes following pullout repair of medial meniscus posterior root tears. METHODS: We retrospectively reviewed the files of 28 patients who had undergone pullout repair of medial meniscus posterior root tears between October 2016 and December 2017. We recorded the baseline characteristics (age, gender, height, weight, and body mass index) and the time between injury and surgery. We recorded the International Knee Documentation Committee scores, Knee injury and Osteoarthritis Outcome Scores, and pain visual analog scale scores. Using magnetic resonance imaging preoperatively and 1 year after surgery, we measured the medial meniscus body width and absolute and relative medial meniscus extrusion. Pearson correlation and multivariate linear regression analyses were used to assess potential associations between these factors and clinical outcomes. RESULTS: Age positively correlated (coefficient = 0.49, P < 0.01) and body mass index negatively correlated with the postoperative International Knee Documentation Committee score (coefficient = -0.64, P < 0.01). In multivariate linear regression analysis, body mass index was a significant factor leading to poor postoperative International Knee Documentation Committee score (R2 = 0.29, P < 0.05). CONCLUSIONS: Body mass index > 30 kg/m2 is a risk factor for unfavorable clinical outcomes following pullout repair of medial meniscus posterior root tears in well-aligned knees. LEVEL OF EVIDENCE: III, Comparative retrospective study.

DOI： 10.1016/j.jos.2020.04.018

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脊椎転移に対する集学的治療麻痺を認めない脊椎SREに対する保存的治療の成績

中田英二, 国定俊之, 藤原智洋, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) JSY39 - 1 2021.5

中等度特発性手根管症候群患者に対する、電気生理学的検査による機能的予後予測の検討

伊勢真人, 本郷匡一, 堅山佳美, 濱田全紀, 千田益生, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) 3 - 2 2021.5

肺癌・食道癌患者の術前におけるがんロコモ・サルコペニアの発生頻度

堅山佳美, 千田益生, 濱田全紀, 中田英二, 伊勢真人, 本郷匡一, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) 2 - 9 2021.5

65歳以下の慢性疼痛患者におけるロコモティブシンドロームと体組成及び運動機能評価

辻寛謙, 三澤治夫, 千田益生, 西田圭一郎, 濱田全紀, 堅山佳美, 鉄永智紀, 小田孔明, 伊勢真人, 梶木裕矢, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) 2 - 7 2021.5

慢性疼痛患者に対するロコモティブシンドローム診断における診断時の特徴及び注意点

辻寛謙, 三澤治夫, 千田益生, 西田圭一郎, 濱田全紀, 堅山佳美, 鉄永智紀, 小田孔明, 伊勢真人, 梶木裕矢, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) 2 - 6 2021.5

周術期のリハビリテーション医療

千田益生, 濱田全紀, 堅山佳美, 伊勢真人, 本郷匡一, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) SL41 - SL41 2021.5

中等度特発性手根管症候群患者に対する、電気生理学的検査による機能的予後予測の検討

伊勢真人, 本郷匡一, 堅山佳美, 濱田全紀, 千田益生, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) 3 - 2 2021.5

肺癌・食道癌患者の術前におけるがんロコモ・サルコペニアの発生頻度

堅山佳美, 千田益生, 濱田全紀, 中田英二, 伊勢真人, 本郷匡一, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) 2 - 9 2021.5

65歳以下の慢性疼痛患者におけるロコモティブシンドロームと体組成及び運動機能評価

辻寛謙, 三澤治夫, 千田益生, 西田圭一郎, 濱田全紀, 堅山佳美, 鉄永智紀, 小田孔明, 伊勢真人, 梶木裕矢, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) 2 - 7 2021.5

慢性疼痛患者に対するロコモティブシンドローム診断における診断時の特徴及び注意点

辻寛謙, 三澤治夫, 千田益生, 西田圭一郎, 濱田全紀, 堅山佳美, 鉄永智紀, 小田孔明, 伊勢真人, 梶木裕矢, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) 2 - 6 2021.5

周術期のリハビリテーション医療

千田益生, 濱田全紀, 堅山佳美, 伊勢真人, 本郷匡一, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) SL41 - SL41 2021.5

脊椎転移に対する集学的治療麻痺を認めない脊椎SREに対する保存的治療の成績

中田英二, 国定俊之, 藤原智洋, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) JSY39 - 1 2021.5

Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression International journal

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 - e0250643 2021.4

Language：English Publishing type：Research paper (scientific journal) Publisher：Public Library of Science (PLoS)

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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A posterior shiny-corner lesion of the tibia is observed in the early phase after medial meniscus posterior root tear. International journal

Yuki Okazaki, Takayuki Furumatsu, Yuya Kajiki, Takaaki Hiranaka, Keisuke Kintaka, Yuya Kodama, Yusuke Kamatsuki, Toshifumi Ozaki

European journal of orthopaedic surgery & traumatology : orthopedie traumatologie 2021.4

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUNDS: Medial meniscus (MM) posterior root tear (PRT) results in joint overloading and degenerative changes in the knee, and pullout repair is recommended to prevent subsequent osteoarthritis. Diagnosing MMPRT is sometimes difficult, especially in the case of an incomplete tear. A posterior shiny-corner lesion (PSCL) is reported to be useful for diagnosis, although the association between MMPRT and PSCL is unknown. This study aimed to investigate the properties of PSCL, such as the location, volume, and duration from injury to the time of MRI (duration). We hypothesized that PSCL is observed in the early phase after the MMPRT onset. METHODS: T2-weighted fat-suppression magnetic resonance imaging (MRI) was obtained from 55 patients with MMPRT preoperatively. The prevalence of the PSCL; giraffe neck, cleft, and ghost signs; severe MM extrusion (> 3 mm); and the PSCL volume were evaluated. The PSCL lesion elliptical volume (mm3) was calculated by measuring the anteroposterior, transverse, and craniocaudal dimensions. RESULTS: PSCL was observed in 34 (62%) cases. The mean volume of the PSCL was 102.0 mm3. A significantly shorter duration was observed in the PSCL-positive group (5.6 weeks) than that in the PSCL-negative group (40.9 weeks, P < 0.01), although no significant correlation was observed between the PSCL volume and duration. The sensitivity for the MMPRT was 90.5% when the cut-off duration value was 3 weeks and 81.8% when the cut-off value was 8 weeks. CONCLUSIONS: MRI examination may detect PSCL if it is performed early following MMPRT onset. Detecting PSCL may be useful in diagnosing MMPRT with high sensitivity.

DOI： 10.1007/s00590-021-02968-4

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Liquid Biopsy Targeting Monocarboxylate Transporter 1 on the Surface Membrane of Tumor-Derived Extracellular Vesicles from Synovial Sarcoma. International journal

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 ) 2021.4

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

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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Papers - OZAKI Toshifumi