Public Library of Science Acta Medica Okayama 1932-6203 19 2 2024 Fluorescence-guided assessment of bone and soft-tissue sarcomas for predicting the efficacy of telomerase-specific oncolytic adenovirus e0298292 EN Koji Uotani Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Center for Innovative Clinical Medicine, Okayama University Hospital Joe Hasei Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aki Yoshida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuaki Yamakawa Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshinori Omori Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhisa Sugiu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Komatsubara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroya Kondo Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Morita Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiro Kiyono Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Suguru Yokoo Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Hata Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Kunisada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Takeda Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 1 2023 Ipsilateral Periprosthetic Fractures above and below the Knee Associated with Navigation Tracker Pin and Bone Fragility 71 74 EN Yasuaki Yamakawa Department of Orthopedic Surgery, Kochi Health Sciences Center Yusuke Kamatsuki Department of Orthopedic Surgery, Kochi Health Sciences Center Tomoyuki Noda Department of Orthopaedic Surgery, Okayama University Hospital Miho Kure Department of Orthopaedic Surgery, Okayama University Hospital Shinichi Miyazawa Department of Orthopaedic Surgery, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital Case Report 10.18926/AMO/64364 We report a case of ipsilateral periprosthetic fractures above and below the knee that occurred at different times due to navigation tracker pin and bone fragility. A 66-year-old Japanese woman with rheumatoid arthritis (RA) underwent a total knee arthroplasty. Four months post-surgery, a periprosthetic fracture above the knee at the navigation pin hole was detected. She underwent osteosynthesis and could walk independently, but she developed an ipsilateral tibial component fracture. Conservative treatment with a splint was followed by bone union. Patients with RA treated with oral steroids tend to develop ipsilateral periprosthetic fractures around the knee due to bone fragility. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4426 13 1 2022 Reliability of the Garden Alignment Index and Valgus Tilt Measurement for Nondisplaced Femoral Neck Fractures 53 EN Yasuaki Yamakawa Department of Orthopedic Surgery, Kochi Health Sciences Center Norio Yamamoto Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yosuke Tomita Department of Physical Therapy, Faculty of Health Care, Takasaki University of Health and Welfare Ryuichiro Okuda Department of Orthopedic Surgery, Kochi Health Sciences Center Yasutaka Masada Department of Orthopedic Surgery, Kochi Health Sciences Center Akihiro Shiroshita Scientific Research Works Peer Support Group (SRWS-PSG) Toshiyuki Matsumoto Department of Orthopedic Surgery, Kochi Health Sciences Center Anteroposterior (AP) alignment assessment for nondisplaced femoral neck fractures is important for determining the treatment strategy and predicting postoperative outcomes. AP alignment is generally measured using the Garden alignment index (GAI). However, its reliability remains unknown. We compared the reliability of GAI and a new AP alignment measurement (valgus tilt measurement [VTM]) using preoperative AP radiographs of nondisplaced femoral neck fractures. The study was designed as an intra- and inter-rater reliability analysis. The raters were four trauma surgeons who assessed 50 images twice. The main outcome was the intraclass correlation coefficient (ICC). To calculate intra- and inter-rater reliability, we used a mixed-effects model considering rater, patient, and time. The overall ICC (95% CI) of GAI and VTM for intra-rater reliability was 0.92 (0.89-0.94) and 0.86 (0.82-0.89), respectively. The overall ICC of GAI and VTM for inter-rater reliability was 0.92 (0.89-0.95), and 0.85 (0.81-0.88), respectively. The intra- and inter-rater reliability of GAI was higher in patients aged <80 years than in patients aged >= 80 years. Our results showed that GAI is a more reliable measurement method than VTM, although both are reliable. Variations in patient age should be considered in GAI measurements. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0344-5704 88 3 2021 Oncolytic virotherapy reverses chemoresistance in osteosarcoma by suppressing MDR1 expression 513 524 EN Kazuhisa Sugiu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joe Hasei Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuaki Yamakawa Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshinori Omori Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Komatsubara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Mochizuki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroya Kondo Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Osaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Fujiwara Center for Innovative Clinical Medicine, Okayama University Hospital Aki Yoshida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Kunisada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Ueda Project for Personalized Cancer Medicine, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research Yasuo Urata Oncolys BioPharma, Inc Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background <br>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.<br><br> Materials and methods <br>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.<br><br> Results <br>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.<br><br> Conclusion <br>Our results suggest that MDR1 is 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. No potential conflict of interest relevant to this article was reported.

Public Library Science Acta Medica Okayama 1932-6203 16 4 2021 Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression e0250643 EN Toshinori Omori Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuaki Yamakawa Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Osaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joe Hasei Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhisa Sugiu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Komatsubara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aki Yoshida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Kunisada Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Urata Oncolys BioPharma, Inc. Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 71 5 2017 Occult Sources of Bleeding in Blunt Trauma : A Narrative Review 363 368 EN Tetsuya Yumoto Advanced Emergency and Critical Care Medical Center, Okayama University Hospital Yoshinori Kosaki Advanced Emergency and Critical Care Medical Center, Okayama University Hospital Yasuaki Yamakawa Advanced Emergency and Critical Care Medical Center, Okayama University Hospital Atsuyoshi Iida Advanced Emergency and Critical Care Medical Center, Okayama University Hospital Hirotsugu Yamamoto Advanced Emergency and Critical Care Medical Center, Okayama University Hospital Taihei Yamada Advanced Emergency and Critical Care Medical Center, Okayama University Hospital Kohei Tsukahara Advanced Emergency and Critical Care Medical Center, Okayama University Hospital Hiromichi Naito Advanced Emergency and Critical Care Medical Center, Okayama University Hospital Takaaki Osako Advanced Emergency and Critical Care Medical Center, Okayama University Hospital Atsunori Nakao Advanced Emergency and Critical Care Medical Center, Okayama University Hospital Review 10.18926/AMO/55433 Worldwide, hemorrhagic shock in major trauma remains a major potentially preventable cause of death. Controlling bleeding and subsequent coagulopathy is a big challenge. Immediate assessment of unidentified bleeding sources is essential in blunt trauma patients with hemorrhagic shock. Chest/pelvic X-ray in conjunction with ultrasonography have been established classically as initial diagnostic imaging modalities to identify the major sources of internal bleeding including intra-thoracic, intra-abdominal, or retroperitoneal hemorrhage related to pelvic fracture. Massive soft tissue injury, regardless of whether isolated or associated with multiple injuries, occasionally causes extensive hemorrhage and acute traumatic coagulopathy. Specific types of injuries, including soft tissue injury or retroperitoneal hemorrhage unrelated to pelvic fracture, can potentially be overlooked or be considered “occult” causes of bleeding because classical diagnostic imaging often cannot exclude such injuries. The purpose of this narrative review article is to describe “occult” or unusual sources of bleeding associated with blunt trauma. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 70 5 2016 The Clinical Application of Hydrogen as a Medical Treatment 331 337 EN Atsuyoshi Iida Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuyuki Nosaka Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tetsuya Yumoto Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Emily Knaup Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromichi Naito Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chihiro Nishiyama Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuaki Yamakawa Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Tsukahara Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Michihisa Terado Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiji Sato Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toyomu Ugawa Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsunori Nakao Department of Emergency and Critical Care Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/54590 In recent years, it has become evident that molecular hydrogen is a particularyl effective treatment for various disease models such as ischemia-reperfusion injury; as a result, research on hydrogen has progressed rapidly. Hydrogen has been shown to be effective not only through intake as a gas, but also as a liquid medication taken orally, intravenously, or locally. Hydrogenʼs effectiveness is thus multifaceted. Herein we review the recent research on hydrogen-rich water, and we examine the possibilities for its clinical application. Now that hydrogen is in the limelight as a gaseous signaling molecule due to its potential ability to inhibit oxidative stress signaling, new research developments are highly anticipated. No potential conflict of interest relevant to this article was reported.