Faculty Profiles - OZAKI Toshifumi

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

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

Scientific reports 7 43604 - 43604 2017.2

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

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.

DOI： 10.1038/srep43604

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Phase 2 study of eribulin in patients with previously treated advanced or metastatic soft tissue sarcoma. International journal

Akira Kawai, Nobuhito Araki, Yoichi Naito, Toshifumi Ozaki, Hideshi Sugiura, Yasuo Yazawa, Hideo Morioka, Akihiko Matsumine, Kenichi Saito, Shun Asami, Kazuo Isu

Japanese journal of clinical oncology 47 ( 2 ) 137 - 144 2017.2

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

Objective: Eribulin, a microtubule dynamics inhibitor, is approved for the treatment of patients with breast cancer and soft tissue sarcoma. We investigated the efficacy and safety of eribulin in Japanese patients with soft tissue sarcoma. Methods: This open-label, multicenter, nonrandomized, Phase 2 study enrolled Japanese patients with measurable, advanced/metastatic soft tissue sarcoma of high/intermediate grade and ≥1 prior chemotherapy for advanced disease. Patients received eribulin mesilate 1.4 mg/m2 intravenously over 2–5 minutes on Days 1 and 8 of a 21-day cycle. The primary endpoint was progression-free rate at 12 weeks. Secondary endpoints included overall survival, progression-free survival and safety. Efficacy analyses were stratified by histology (liposarcoma or leiomyosarcoma, and other subtypes). Results: Overall, 52 patients were enrolled and 51 patients were treated. Patients with liposarcoma/leiomyosarcoma (n = 35) had similar characteristics to those with other subtypes (n = 16), except for a higher proportion of women (63% vs 38%, respectively) and patients with Eastern Cooperative Oncology Group performance status 0 (57% vs 44%). Progression-free rate at 12 weeks was 60% in liposarcoma/leiomyosarcoma patients, 31% in other subtypes and 51% overall. Median progression-free survival was 5.5 months in liposarcoma/leiomyosarcoma patients, 2.0 months in other subtypes and 4.1 months overall. Median overall survival was 17.0 months in liposarcoma/leiomyosarcoma patients, 7.6 months in other subtypes and 13.2 months overall. The most common Grade 3–4 adverse events were neutropenia (86%), leukopenia (75%), lymphopenia (33%), anemia (14%) and febrile neutropenia (8%). Conclusion: Eribulin showed clinical activity with a manageable safety profile in previously treated Japanese patients with advanced/metastatic soft tissue sarcoma.

DOI： 10.1093/jjco/hyw175

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Results of Total Elbow Arthroplasty with Cementless Implantation of an Alumina Ceramic Elbow Prosthesis for Patients with Rheumatoid Arthritis.

Keiichiro Nishida, Kenzo Hashizume, Masatsugu Ozawa, Ayumu Takeshita, Daisuke Kaneda, Ryuichi Nakahara, Yoshihisa Nasu, Yasunori Shimamura, Hajime Inoue, Toshifumi Ozaki

Acta medica Okayama 71 ( 1 ) 41 - 47 2017.2

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

We investigated the long-term clinical results of total elbow arthroplasty (TEA) by cementless fixation of alumina ceramic unlinked elbow prostheses (J-alumina ceramic elbows: JACE) for the reconstruction of elbow joints with rheumatoid arthritis (RA). Seventeen elbows in 17 patients (aged 44-72 years, average 54.8) replaced by JACE TEA without bone cement were investigated. The average follow-up period was 10.7 (range, 1.0-19.3) years. Clinical conditions of each elbow before and after surgery were assessed according to the Mayo Elbow Performance Index (MEPI). Radiographic loosening was defined as a progressive radiolucent line of more than 1 mm that was completely circumferential around the intramedullary stem. The average MEPI significantly improved from 46.8 points preoperatively to 66.8 points at final follow-up (p=0.0226). However, aseptic loosening was noted in 10 of 17 elbows (58.8%) and revision surgery was required in 7 (41.2%). Most loosening was observed on the humeral side. With radiographic loosening and revision surgery defined as the end points, the likelihoods of prosthesis survival were 41.2% and 51.8%, respectively, up to 15 years by Kaplan-Meier analysis. The clinical results of JACE implantation without bone cement were disappointing, with high revision and loosening rates of the humeral component.

DOI： 10.18926/AMO/54824

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Verification of Implant Surface Modification by a Novel Processing Method.

Yoshiki Okada, Nobuhiro Abe, Noriyuki Hisamori, Toshiaki Kaneeda, Shigeaki Moriyama, Hitoshi Ohmori, Masayoshi Mizutani, Hiroyuki Yanai, Yoshio Nakashima, Yusuke Yokoyama, Toshifumi Ozaki

Acta medica Okayama 71 ( 1 ) 49 - 57 2017.2

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

Metals have been used clinically as biomaterials, especially in the orthopaedic and dental fields. Metals used as implants wear at contact surfaces, producing metal particles and metal ions that may be harmful. Newly developed metal implants and methods of implant surface modification are currently under scrutiny. We evaluated the use of electrolytic in-process dressing (ELID) as a surface finishing method for metal implants. Metal implants processed using the ELID method (ELID group) or not processed (Non-ELID group) were inserted surgically into rabbit femurs. The rabbits were sacrificed postoperatively over a 24-week period. We assessed the concentrations of the cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, the resistance to implant pull-out, and histopathology at the implant site. There was no significant difference between the groups regarding the cytokine concentrations or implant pull-out resistance. Many particles indicating wear around the implant were noted in the Non-ELID group (n=10) but not the ELID group (n=13), while a fibrous membrane adhering to the every implant was noted in the ELID group. The formation of a fibrous membrane rather than metal particles in the ELID group may indicate improved biocompatibility, and it suggests that ELID may prevent corrosion in the areas of contact.

DOI： 10.18926/AMO/54825

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肘関節投球障害に対する関節造影ストレス撮影の有用性

島村安則, 内野崇彦, 島村好信, 中道亮, 井上博登, 名越充, 雑賀建多, 古松毅之, 野田知之, 尾崎敏文

日本肘関節学会雑誌 24 ( 1 ) S106 - S106 2017.1

上腕骨小頭離断性骨軟骨炎に対する内側支持機構のゆるみの影響

内野崇彦, 島村安則, 島村好信, 中道亮, 井上博登, 名越充, 雑賀建多, 古松毅之, 野田知之, 尾崎敏文

日本肘関節学会雑誌 24 ( 1 ) S18 - S18 2017.1

Calcar femorale in patients with osteoarthritis of the hip secondary to developmental dysplasia Reviewed

Tomonori Tetsunaga, Kazuo Fujiwara, Hirosuke Endo, Tomoko Tetsunaga, Naofumi Shiota, Toru Sato, Toshifumi Ozaki

CiOS Clinics in Orthopedic Surgery 9 ( 4 ) 413 - 419 2017

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Papers - OZAKI Toshifumi