Faculty Profiles - KUNISADA Toshiyuki

Papers - KUNISADA Toshiyuki

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骨肉腫における細胞内外microRNA-25-3p発現の機能解析

吉田晶, 藤原智洋, 魚谷弘二, 森田卓也, 清野正普, 横尾賢, 長谷井嬢, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 92 ( 8 ) S1813 - S1813 2018.8

骨肉腫の細胞内外microRNA-25-3p発現異常の腫瘍学的意義

吉田晶, 藤原智洋, 魚谷弘二, 森田卓也, 清野正普, 横尾賢, 長谷井嬢, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 92 ( 6 ) S1460 - S1460 2018.6

前腕悪性腫瘍に対する術後の作業療法を施行した1例

岡佳純, 松山宜之, 堅山佳美, 国定俊之, 千田益生

The Japanese Journal of Rehabilitation Medicine 55 ( 特別号 ) 3 - 1 2018.5

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

Yoshida A, Fujiwara T, Uotani K, Morita T, Kiyono M, Yokoo S, Hasei J, Nakata E, Kunisada T, Ozaki T

Acta medica Okayama 72 ( 2 ) 165 - 174 2018.4

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

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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【運動器画像診療の最前線】部位別・疾患別画像診療の最前線骨腫瘍の画像診療

中田英二, 国定俊之, 長谷井嬢, 藤原智洋, 尾崎敏文

関節外科 37 ( 4月増刊 ) 130 - 143 2018.4

Language：Japanese Publisher：(株)メジカルビュー社

＜画像診療のポイント＞●骨腫瘍の診療において、画像検査は鑑別診断や治療効果判定だけではなく、手術にも有用である。●鑑別診断について、初診医は一般整形外科医であることが多く、悪性を疑う所見を見逃さないことが重要である。●骨腫瘍にはそれぞれ特徴的な年齢分布や好発部位があり、年齢や既往歴などの臨床情報も踏まえ、複数の画像検査の情報を組み合わせて診断を行う。●単純X線像の読影では、腫瘍の局在と性状に注目する。●CTは、単純X線検査では評価が困難な部位の診断、微細な石灰化や骨化の有無の検出などを調べるのに適している。また、三次元的に骨病変を評価することができ、術前計画にも有用である。さらに、近年はコンピュータ支援手術により術中に短時間で高画質の2D・3D画像が取得でき、画像データをナビゲーションシステムに送信することで、より低侵襲かつ安全で確実な手術が可能となっている。●MRIは優れたコントラスト分解能をもち、腫瘍の進展や質的診断、治療効果判定などに有用である。●PET/CTは、良悪性の鑑別診断、病期診断、治療効果判定に有用である。●各画像検査には長所と短所があるため、その特徴を理解しておくことが重要である。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00282&link_issn=&doc_id=20180406150013&doc_link_id=10.18885%2FJ00282.2018192551&url=https%3A%2F%2Fdoi.org%2F10.18885%2FJ00282.2018192551&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

脊椎に原発した骨肉腫の5例

塩崎泰之, 瀧川朋亨, 三澤治夫, 尾崎敏文, 中田英二, 国定俊之

中国・四国整形外科学会雑誌 30 ( 1 ) 79 - 82 2018.4

Language：Japanese Publisher：中国・四国整形外科学会

当院で経験した脊椎原発の骨肉腫5例(男性2例、女性3例、診断時平均年齢52歳)について検討した。発生高位はT1が1例、L2が1例、L3が1例、L5が2例であった。初診時の症状は腰椎発生の3例では全例に腰痛が認められ、2例に下肢不全麻痺が合併していた。胸椎発生の2例では、それぞれ背部痛と上肢痛を認められた。治療は全摘出術を2例、重粒子線治療を3例に行った。また、化学療法は4例に行った。予後は、治療中の2例を除き、3例は診断後平均66ヵ月で死亡していた。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J02438&link_issn=&doc_id=20180621090018&doc_link_id=%2Fcm4ortho%2F2018%2F003001%2F018%2F0079-0082%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcm4ortho%2F2018%2F003001%2F018%2F0079-0082%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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 2018.3

Patients with osteosarcoma and soft tissue sarcoma might become “cancer refugees” in some japanese regional cities Reviewed

Hiromichi Yamane, Toshiyuki Kunisada, Toshifumi Ozaki, Nobuaki Ochi, Yoshihiro Honda, Yasunari Nagasaki, Nozomu Nakagawa, Tomoko Yamagishi, Hidekazu Nakanishi, Nagio Takigawa

Cancer Management and Research 10 353 - 359 2018.2

Language：English Publishing type：Research paper (scientific journal) Publisher：Dove Medical Press Ltd

Purpose: “Rare cancer” is defined as malignancy with a disease prevalence (age-adjusted incidence rate) of less than six per 100,000 population. Proper treatments which these patients need cannot always be performed unless they find dedicated facilities. Patients tend to be desperate, searching for advice and care. Thus, they are called “cancer refugees”. Osteosarcoma and soft tissue sarcoma (OS/STS) are representative rare cancers in Japan. We conducted a retrospective analysis of patients with OS/STS to improve the current treatment modalities in a Japanese regional city. Patients and methods: Twenty-one patients with OS/STS who were hospitalized to receive standard chemotherapy or palliative treatment were enrolled between October 2011 and January 2017. Patients with non-Hodgkin’s lymphoma (NHL) and advanced cancer who were treated in the palliative care unit (PCU) of the Kawasaki Medical School General Medical Center were recruited as the control groups. We analyzed the difference in residential area between patients with OS/STS and the control groups. Results: Approximately one-third of patients with OS/STS were referred from hospitals outside of Okayama prefecture. The ratio of patients with OS/STS referred from Okayama city and/or the same medical administration area of Okayama prefecture was lower than that of patients with NHL and advanced cancer who were treated in the PCU. Conclusion: Because the medical environment of patients with OS/STS in Japanese local cities has not been consolidated, completing medical care within the patient’s own medical administration area is difficult. Thus, some patients with OS/STS may become “cancer refugees” who are unable to receive standard therapy near their residence.

DOI： 10.2147/CMAR.S155282

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Molecular radiosensitization of p53-armed telomerase-dependent oncolytic adenovirus against human soft-tissue sarcoma

Tadashi Komatsubara, Hiroshi Tazawa, Yusuke Mochizuki, Kazuhisa Sugiu, Toshinori Omori, Yasuaki Yamakawa, Syuhei Osaki, Joe Hasei, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara

CANCER SCIENCE 109 454 - 454 2018.1

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 2018.1

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

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

Journal of Orthopaedic Science 2018

Circulating MicroRNA-92b-3p as a Novel Biomarker for Monitoring of Synovial Sarcoma Reviewed

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 2017.11

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

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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地方都市における希少がん標準的化学療法の取り組み骨軟部腫瘍化学療法の現状

山根弘路, 越智宣昭, 本多宣裕, 山岸智子, 中川望, 長崎泰有, 国定俊之, 藤原智洋, 長谷井嬢, 尾崎敏文, 瀧川奈義夫

日本癌治療学会学術集会抄録集 55回 P42 - 4 2017.10

Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction Reviewed

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 2017.9

Language：English Publishing type：Research paper (scientific journal) Publisher：Blackwell Publishing Ltd

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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Factors associated with the decision of operative procedure for proximal femoral bone metastasis: Questionnaire survey to institutions participating the Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group Reviewed

Nobuhito Araki, Hirokazu Chuman, Tomoya Matsunobu, Kazuhiro Tanaka, Hirohisa Katagiri, Toshiyuki Kunisada, Toru Hiruma, Hiroaki Hiraga, Hideo Morioka, Hiroshi Hatano, Kunihiro Asanuma, Yoshihiro Nishida, Koji Hiraoka, Takeshi Okamoto, Satoshi Abe, Munenori Watanuki, Takeshi Morii, Hideshi Sugiura, Yukihiro Yoshida, Takatoshi Ohno, Hidetatsu Outani, Koichiro Yokoyama, Shoji Shimose, Haruhiko Fukuda, Yukihide Iwamoto

JOURNAL OF ORTHOPAEDIC SCIENCE 22 ( 5 ) 938 - 945 2017.9

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER JAPAN KK

Background: Pathological fracture of the proximal femur is a main cause of cancer patients losing their ability to walk. Although both osteosynthetic devices (predominantly intramedullary nails) and prosthetic replacement have been widely performed for treatment, controversies exist regarding which procedure should be used for the various conditions. In order to decide the eligibility criteria of a planned randomized prospective study about the treatment of pathological fractures of the proximal femur, we assessed the factors affecting the selection of operative procedures using questionnaires sent to the members of the Bone and Soft Tissue Tumor Study Group (BSTTSG) of the Japan Clinical Oncology Group (JCOG).
Methods: Questionnaire surveys to evaluate (1) the priority levels of the factors, (2) the equipoise range of each factor in situations where either procedure could be applied, (3) risk and benefit of each procedure, and (4) the degree of bone destruction affecting the selection of operative procedures, were sent to 26 institutions.
Results: Over 80% of the institutions answered. Orthopaedic surgeons of BSTTSG decided on the procedure according to the following factors in descending order: life expectancy, performance status before fracture, the degree of bone destruction, walking ability before fracture, general complications, the number of bone metastases in other sites, and the visceral metastasis status. With regard to bone destruction, (1) the involvement of the head, neck, calcar, and intertrochanteric region, (2) transverse destruction >1/2, and (3) soft-tissue tumor extension, were the factors that led to the choice of prosthesis treatment.
Conclusions: Using these identified factors, the inclusion criteria for the prospective randomized study of the surgical treatment of metastatic bone tumors of the proximal femur were optimized. The evaluation system about the bone destruction of metastases needs to be refined through the following prospective randomized study. (C) 2017 The Authors. Published by Elsevier B.V. on behalf of The Japanese Orthopaedic Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

DOI： 10.1016/j.jos.2017.05.012

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Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction Reviewed

CANCER SCIENCE 108 ( 9 ) 1870 - 1880 2017.9

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

DOI： 10.1111/cas.13316

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悪性骨軟部腫瘍に対する治療の進歩術中ナビゲーションシステムを併用した悪性骨軟部腫瘍手術

国定俊之, 藤原智洋, 長谷井嬢, 瀧川朋亨, 尾崎敏文