International Institute of Anticancer Research Acta Medica Okayama 0250-7005 46 1 2025 P53-Armed Oncolytic Virotherapy Promotes the Efficacy of PD1 Blockade in Murine Osteosarcoma Tumors 69 84 EN MIHO KURE 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 KOJI DEMIYA 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 YUSUKE MOCHIZUKI 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 AKI YOSHIDA Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences KOJI UOTANI 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 TOMOHIRO FUJIWARA 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 Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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 Background/Aim: Osteosarcoma (OS) is refractory to immune checkpoint inhibitors targeting programmed cell death 1 (PD1)/PD ligand 1 (PD-L1) due to poor immune response. We previously developed telomerase-specific, replication-competent oncolytic adenoviruses non-armed OBP-301 and P53-armed OBP-702 that exert antitumor efficacy against human OS cells. Recently, we demonstrated that P53-armed OBP-702 induces more profound immunogenic cell death and antitumor immune response against human and murine OS cells than does non-armed OBP-301. In the present study, we assessed the combined efficacy of PD1 blockade and P53-armed OBP-702 against murine OS cells. Materials and Methods: Three murine OS cell lines (K7M2, NHOS, NHOS-LM4) were used to assess the cytopathic effect of non-armed OBP-301 and P53-armed OBP-702 by XTT assay. Virus-induced immunogenic cell death was assessed by analyzing the levels of extracellular adenosine triphosphate and high-mobility group box protein B1. The expression of PD-L1 and PD-L2 was analyzed by flow cytometry. The malignant potential of NHOS-LM4 cells was analyzed by a migration and invasion assay. An orthotopic NHOS-LM4 tumor model was used to evaluate the antitumor efficacy of combination therapy with P53-armed OBP-702 and anti-PD1. Results: P53-armed OBP-702 exhibited antitumor potential for the induction of immunogenic cell death, apoptosis, autophagy, and PD-L1/2 upregulation in K7M2 and NHOS cells. NHOS-LM4 cells showed increased migratory and invasive ability compared to NHOS cells. P53-armed OBP-702 significantly suppressed the malignant potential of NHOS-LM4 cells. Combination dosing showed that P53-armed OBP-702 significantly promoted the antitumor effect of PD1 blockade against NHOS-LM4 tumors. Conclusion: Our results suggest that P53-armed OBP-702 is a promising agent for improving the antitumor effect of PD1 blockade in treating invasive OS. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6694 17 19 2025 Utility of Same-Modality, Cross-Domain Transfer Learning for Malignant Bone Tumor Detection on Radiographs: A Multi-Faceted Performance Comparison with a Scratch-Trained Model 3144 EN Joe Hasei Department of Medical Informatics and Clinical Support Technology Development, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryuichi Nakahara Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yujiro Otsuka Department of Radiology, Juntendo University School of Medicine Koichi Takeuchi Graduate School of Environmental, Life Natural Science and Technology, Okayama University Yusuke Nakamura Plusman LCC Kunihiro Ikuta Department of Orthopedic Surgery, Graduate School of Medicine, Nagoya University Shuhei Osaki Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital Hironari Tamiya Department of Musculoskeletal Oncology Service, Osaka International Cancer Institute, Shinji Miwa Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University Shusa Ohshika Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine Shunji Nishimura Department of Orthopaedic Surgery, Kindai University Hospital Naoaki Kahara Department of Orthopedic Surgery, Mizushima Central Hospital Aki Yoshida Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroya Kondo Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Fujiwara Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyuki Kunisada Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshifumi Ozaki Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Developing high-performance artificial intelligence (AI) models for rare diseases like malignant bone tumors is limited by scarce annotated data. This study evaluates same-modality cross-domain transfer learning by comparing an AI model pretrained on chest radiographs with a model trained from scratch for detecting malignant bone tumors on knee radiographs. Methods: Two YOLOv5-based detectors differed only in initialization (transfer vs. scratch). Both were trained/validated on institutional data and tested on an independent external set of 743 radiographs (268 malignant, 475 normal). The primary outcome was AUC; prespecified operating points were high-sensitivity (≥0.90), high-specificity (≥0.90), and Youden-optimal. Secondary analyses included PR/F1, calibration (Brier, slope), and decision curve analysis (DCA). Results: AUC was similar (YOLO-TL 0.954 [95% CI 0.937–0.970] vs. YOLO-SC 0.961 [0.948–0.973]; DeLong p = 0.53). At the high-sensitivity point (both sensitivity = 0.903), YOLO-TL achieved higher specificity (0.903 vs. 0.867; McNemar p = 0.037) and PPV (0.840 vs. 0.793; bootstrap p = 0.030), reducing ~17 false positives among 475 negatives. At the high-specificity point (~0.902–0.903 for both), YOLO-TL showed higher sensitivity (0.798 vs. 0.764; p = 0.0077). At the Youden-optimal point, sensitivity favored YOLO-TL (0.914 vs. 0.892; p = 0.041) with a non-significant specificity difference. Conclusions: Transfer learning may not improve overall AUC but can enhance practical performance at clinically crucial thresholds. By maintaining high detection rates while reducing false positives, the transfer learning model offers superior clinical utility. Same-modality cross-domain transfer learning is an efficient strategy for developing robust AI systems for rare diseases, supporting tools more readily acceptable in real-world screening workflows. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1341-9625 2025 Advances in liquid biopsy for bone and soft-tissue sarcomas EN Yilang Wang 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 Takanao Kurozumi Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Teruhiko Ando Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takahiko Ishimaru 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 Eiji Nakata 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 Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Bone and soft-tissue sarcomas are a heterogeneous group of malignant tumors originating from mesenchymal tissues, accounting for approximately 1% of adult solid malignancies and 20% of pediatric solid malignancies. While blood-based tumor markers are available in major types of cancers, evidence demonstrating useful circulating biomarkers is limited in bone and soft-tissue sarcomas. Despite the development of combined modality treatments, a significant proportion of sarcoma patients respond poorly to chemotherapy or radiotherapy, leading to local relapse or distant metastasis. However, imaging methods, such as X-ray, computed tomography, positron emission tomography, magnetic resonance imaging, and scintigraphy, are mostly used to detect or monitor tumor development. Liquid biopsy is an emerging minimally invasive diagnostic technique that detects tumor-derived molecules in body fluids, including circulating tumor cells, circulating tumor DNA (ctDNA), circulating tumor RNA (ctRNA), and circulating extracellular vesicles. This method offers new possibilities for early tumor detection, prognostic evaluation, and therapeutic monitoring and may serve as a benchmark for treatment modification. This review focuses on the current technological advances in liquid biopsy for bone and soft-tissue sarcoma and explores its potential role in guiding personalized treatments. If these modalities could determine resistance to ongoing therapy or the presence of minimal residual disease at the end of the treatment protocol, the obtained data would be important for determining whether to change treatment approaches or add adjuvant therapies. No potential conflict of interest relevant to this article was reported.

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.

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 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 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.

MDPI Acta Medica Okayama 2072-6694 13 5 2021 Role of Tumor-Associated Macrophages in Sarcomas 1086 EN Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences John Healey Department of Surgery, Orthopaedic Service, Memorial Sloan Kettering Cancer Center Koichi Ogura Department of Surgery, Orthopaedic Service, Memorial Sloan Kettering Cancer Center Aki Yoshida 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 Toshiaki Hata Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Miho Kure 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 Eiji Nakata 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 Toshiyoshi Fujiwara Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Hospital Simple Summary Recent studies have shown the pro-tumoral role of tumor-associated macrophages (TAMs) not only in major types of carcinomas but also in sarcomas. Several types of TAM-targeted drugs have been investigated under clinical trials, which may represent a novel therapeutic approach for bone and soft-tissue sarcomas. Sarcomas are complex tissues in which sarcoma cells maintain intricate interactions with their tumor microenvironment. Tumor-associated macrophages (TAMs) are a major component of tumor-infiltrating immune cells in the tumor microenvironment and have a dominant role as orchestrators of tumor-related inflammation. TAMs promote tumor growth and metastasis, stimulate angiogenesis, mediate immune suppression, and limit the antitumor activity of conventional chemotherapy and radiotherapy. Evidence suggests that the increased infiltration of TAMs and elevated expression of macrophage-related genes are associated with poor prognoses in most solid tumors, whereas evidence of this in sarcomas is limited. Based on these findings, TAM-targeted therapeutic strategies, such as inhibition of CSF-1/CSF-1R, CCL2/CCR2, and CD47/SIRP alpha, have been developed and are currently being evaluated in clinical trials. While most of the therapeutic challenges that target sarcoma cells have been unsuccessful and the prognosis of sarcomas has plateaued since the 1990s, several clinical trials of these strategies have yielded promising results and warrant further investigation to determine their translational benefit in sarcoma patients. This review summarizes the roles of TAMs in sarcomas and provides a rationale and update of TAM-targeted therapy as a novel treatment approach for sarcomas. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0340-7004 70 2020 Telomerase-specific oncolytic immunotherapy for promoting efficacy of PD-1 blockade in osteosarcoma 1405 1417 EN Yusuke Mochizuki Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Demiya Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Miho Kure Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroya Kondo Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadashi Komatsubara Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhisa Sugiu Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Joe Hasei Sports Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Aki Yoshida Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyuki Kunisada Medical Materials for Musculoskeletal Reconstruction, Okayama University Graduate School of Medicine Yasuo Urata Oncolys BioPharma, Inc, Shunsuke Kagawa Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Departments of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 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. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 23526440 25 2020 The Masquelet technique for septic arthritis of the small joint in the hands: Case reports 100268 EN Taichi Saito Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Tomoyuki Noda Department of Musculoskeletal Traumatology, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Hiroya Kondo Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Koji Demiya Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Satoshi Nezu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Suguru Yokoo Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Minami Matsuhashi Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Takenori Uehara Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Yasunori Shimamura Department of Sports Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Masayuki Kodama Mizushima Central Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Septic arthritis in distal interphalangeal (DIP) joints sometimes occurs in association with mucous cysts or after the surgical treatment of mallet fingers. Recently, several studies have demonstrated the effectiveness of the Masquelet technique in the treatment of bone defects caused by trauma or infection. However, only few studies have reported the use of this technique for septic arthritis in small joints of the hand, and its effectiveness in treating septic arthritis in DIP joints remains unclear. We report the clinical and radiological outcomes of three patients who were treated with the Masquelet technique for septic arthritis in DIP joints. One patient had uncontrolled diabetes and another had rheumatoid arthritis treated with methotrexate and prednisolone. The first surgical stage involved thorough debridement of the infection site, including the middle and distal phalanx. We placed an external fixator from the middle to the distal phalanx and then packed the cavity of the DIP joint with antibiotic cement bead of polymethylmethacrylate (40 g) including 2 g of vancomycin and 200 mg of minocycline. At 4-6 weeks after the first surgical stage, the infection had cleared, and the second surgical stage was performed. The external fixator and cement bead were carefully removed while carefully preserving the surrounding osteo-induced membrane. The membrane was smooth and nonadherent to the cement block. In the second surgical stage, an autogenous bone graft was harvested from the iliac bone and inserted into the joint space, within the membrane. The bone graft, distal phalanx, and middle phalanx were fixed with Kirschner wires and/or a soft wire. Despite the high risk of infection, bone union was achieved in all patients without recurrence of infection. Although the Masquelet technique requires two surgeries, it can lead to favorable clinical and radiological outcomes for infected small joints of the hand. No potential conflict of interest relevant to this article was reported.