Publishing type：Research paper (scientific journal)   Publisher：Cureus, Inc.  

DOI： 10.7759/cureus.33110

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(一社)日本関節病学会  

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Language：English  

DOI： 10.1016/j.jos.2018.12.030

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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 an 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.

DOI： 10.1007/s00280-021-04310-5

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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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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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Publishing type：Research paper (scientific journal)  

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Other Link： https://dblp.uni-trier.de/db/journals/corr/corr2110.html#abs-2110-08509

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

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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Unidirectional porous hydroxyapatite (UDPHAp) was developed as an excellent scaffold with unidirectional pores oriented in the horizontal direction with interpore connections. The purpose of this study was to assess radiographic changes and clinical outcomes and complications following UDPHAp implantation to treat benign bone tumors. We retrospectively analyzed 44 patients treated with intralesional resection and UDPHAp implantation for benign bone tumors between 2010 and 2015. Clinical and radiographic findings were evaluated postoperatively at regular follow-up visits. The mean follow-up was 49 months. Radiographic changes were classified into five stages based on bone formation in the implanted UDPHAp according to Tamai's classification. All patients showed excellent bone formation inside and around implanted UDPHAp. Absorption of UDPHAp and bone marrow cavity remodeling was identified in 20 patients at a mean of 17 months postoperatively, and was significantly more common in young patients. Preoperative cortical thinning was completely regenerated in 26 of 31 patients on average 10 months after surgery. There were no cases of delayed wound healing, postoperative infection, or allergic reaction related to implanted UDPHAp. UDPHAp is a useful bone-filling substitute for treating benign bone tumor, and the use of this material has a low complication rate.

DOI： 10.1038/s41598-020-78409-9

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BACKGROUND: Dedifferentiated liposarcoma (DDLPS) is a rare malignancy that transitions from an atypical lipomatous tumor to a sarcoma with a variable morphologic appearance. The behavior of this tumor in the retroperitoneum is aggressive, but the behavior of DDLPS in the extremities is less well-defined because it is rare. Few reports have assessed the imaging features and clinical outcomes of primary DDLPS in the extremities. QUESTIONS/PURPOSES: In patients with primary DDLPS of the extremity, we asked the following questions: (1) How frequently do additional primary malignancies occur in patients with DDLPS? (2) What is the rate of overall survival, metastases, and local recurrence in DDLPS? (3) What factors are associated with metastasis-free survival and local recurrence in DDLPS? METHODS: We defined DDLPS as a biphasic neoplasm that transitions from an atypical lipomatous tumor (ALT) to a sarcoma of variable morphologic appearance and histologic grades. We retrospectively evaluated the medical records of patients with DDLPS of the extremities who underwent surgery in our institution between 2003 and 2017. During that time, 16 patients were treated for this diagnosis; one was excluded from this study because the patient did not have an MRI, leaving 15 patients (nine men, six women; their median [range] age was 67 years [42 to 87]) for evaluation. All had a minimum of 2 years follow-up (median [range] 54 months [25 to 136]); 14 of 15 have been seen in the last 5 years (one patient, who was doing well at the time, was lost after 9 years of follow-up). In 11 patients, MRI demonstrated two components: an ALT component with high intensity on both T1-weighed and T2-weighted sequences and a dedifferentiated component low-to-intermediate intensity on T1-weighed and heterogeneous hyperintensity on T2-weighted sequence. Nine patients were evaluated using 2-deoxy-2-18F-fluoro-D-glucose positron emission tomography (FDG-PET) combined with CT (PET/CT). PET/CT showed a biphasic pattern with a close relationship to MRI findings. The dedifferentiated component presented with high FDG uptake (median [range] maximum standardized uptake value 5.1 [1.9 to 22.6]), while the atypical lipomatous tumor component showed almost no FDG uptake. In all patients, immunohistochemical studies of p16 and cyclin-dependent kinase-4 (CDK4) were investigated. Positive staining for both p16 and CDK4 were seen in 13 of 15 patients.We retrospectively evaluated the electronic medical records of all patients in our institution for the presence of additional primary malignancies, local recurrence-free survival, metastasis-free survival, and overall survival. The survival rate was estimated using the Kaplan-Meier method. The Wilcoxon exact test was used to determine the prognostic importance of the following survival variables: age, sex, maximum tumor size, radiotherapy, and surgical margin. RESULTS: Seven additional primary malignancies developed in five of 15 patients (two lung cancers, two sarcomas, one renal cell cancer, one uterine cancer, and one non-Hodgkin lymphoma). The 3- and 5-year metastasis-free survival rates were 86% (95% CI 0.67 to 1.00) and 75% (95% CI 0.49 to 1.00), respectively. With the numbers available, we found no factors associated with metastasis-free survival. The 3- and 5-year overall survival rates were 100% (95% CI 1.00 to 1.00) and 88% (95% CI 0.65 to 1.00), respectively. Three of 15 patients had local recurrence. The 3- and 5-year local recurrence-free survival rates were 86% (95% CI 0.67 to 1.00) and 75% (95% CI 0.49 to 1.00), respectively. Large (> 15 cm) tumors were more likely to have a local recurrence (p = 0.04). CONCLUSIONS: In this small series, we found that the extremities are a favorable site for DDLPS compared with the retroperitoneum, although we did not directly compare the two sites. This rare tumor has a relatively high likelihood of being associated with other malignancies. We believe patients should be assessed and monitored carefully for this possibility. In the future, larger studies are needed to better define predictors of local recurrence, although the tumor's size may be associated with a greater propensity for local recurrence. LEVEL OF EVIDENCE: Level II, prognostic study.

DOI： 10.1097/CORR.0000000000001338

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Meniscus tears are common knee injuries and a major osteoarthritis (OA) risk factor. Knowledge gaps that limit the development of therapies for meniscus injury and degeneration concern transcription factors that control the meniscus cell phenotype. Analysis of RNA sequencing data from 37 human tissues in the Genotype-Tissue Expression database and RNA sequencing data from meniscus and articular cartilage showed that transcription factor Mohawk (MKX) is highly enriched in meniscus. In human meniscus cells, MKX regulates the expression of meniscus marker genes, OA-related genes, and other transcription factors, including Scleraxis (SCX), SRY Box 5 (SOX5), and Runt domain-related transcription factor 2 (RUNX2). In mesenchymal stem cells (MSCs), the combination of adenoviral MKX (Ad-MKX) and transforming growth factor-β3 (TGF-β3) induced a meniscus cell phenotype. When Ad-MKX-transduced MSCs were seeded on TGF-β3-conjugated decellularized meniscus scaffold (DMS) and inserted into experimental tears in meniscus explants, they increased glycosaminoglycan content, extracellular matrix interconnectivity, cell infiltration into the DMS, and improved biomechanical properties. Ad-MKX injection into mouse knee joints with experimental OA induced by surgical destabilization of the meniscus suppressed meniscus and cartilage damage, reducing OA severity. Ad-MKX injection into human OA meniscus tissue explants corrected pathogenic gene expression. These results identify MKX as a previously unidentified key transcription factor that regulates the meniscus cell phenotype. The combination of Ad-MKX with TGF-β3 is effective for differentiation of MSCs to a meniscus cell phenotype and useful for meniscus repair. MKX is a promising therapeutic target for meniscus tissue engineering, repair, and prevention of OA.

DOI： 10.1126/scitranslmed.aan7967

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Infiltrative tumor growth into adjacent soft tissues is a major cause of the frequent recurrence and tumor-related death of myxofibrosarcoma (MFS), but no useful biomarkers reflecting tumor burden and infiltrative growth are available. While emerging evidence suggests a diagnostic and functional role of extracellular/circulating microRNA (miRNA) in various malignant diseases, their significance in MFS patients remains unknown. Global miRNA profiling identified four upregulated miRNAs in MFS patient sera and culture media of MFS cells. Among these, serum miR-1260b level was significantly upregulated in patient serum discriminating from healthy individuals and closely correlated with clinical status and tumor dynamics in MFS-bearing mice. In addition, high miR-1260b expression in serum was correlated with radiological tail-like patterns, characteristic of the infiltrative MFS. The extracellular miR-1260b was embedded in tumor-derived extracellular vesicles (EVs) and promoted cellular invasion of MFS through the downregulation of PCDH9 in the adjacent normal fibroblasts. Collectively, circulating miR-1260b expression may represent a novel diagnostic target for tumor monitoring of this highly aggressive sarcoma. Moreover, EV-miR-1260b could act as a transfer messenger to adjacent cells and mediate the infiltrative growth of MFS, providing new insights into the mechanism of infiltrative nature via crosstalk between tumor cells and their microenvironment.

DOI： 10.1038/s41598-020-66120-8

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Adenovirus serotype 5 (Ad5) is widely and frequently used as a virus vector in cancer gene therapy and oncolytic virotherapy. Oncolytic virotherapy is a novel antitumor treatment for inducing lytic cell death in tumor cells without affecting normal cells. Based on the Ad5 genome, we have generated three types of telomerase-specific replication-competent oncolytic adenoviruses: OBP-301 (Telomelysin), green fluorescent protein (GFP)-expressing OBP-401 (TelomeScan), and tumor suppressor p53-armed OBP-702. These viruses drive the expression of the adenoviral E1A and E1B genes under the control of the hTERT (human telomerase reverse transcriptase-encoding gene) promoter, providing tumor-specific virus replication. This review focuses on the therapeutic potential of three hTERT promoter-driven oncolytic adenoviruses against bone and soft-tissue sarcoma cells with telomerase activity. OBP-301 induces the antitumor effect in monotherapy or combination therapy with chemotherapeutic drugs via induction of autophagy and apoptosis. OBP-401 enables visualization of sarcoma cells within normal tissues by serving as a tumor-specific labeling reagent for fluorescence-guided surgery via induction of GFP expression. OBP-702 exhibits a profound antitumor effect in OBP-301-resistant sarcoma cells via activation of the p53 signaling pathway. Taken together, telomerase-specific oncolytic adenoviruses are promising antitumor reagents that are expected to provide novel therapeutic options for the treatment of bone and soft-tissue sarcomas.

DOI： 10.3390/cancers12020478

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BACKGROUND: The choice of reconstructive procedure to restore limb function is challenging after internal hemipelvectomy. Hip transposition arthroplasty, also known as resection arthroplasty, removes a malignant or aggressive tumor of the pelvis and acetabulum after which the remaining femoral head is moved proximally to the lateral surface side of the sacrum or the underside of the resected ilium after internal hemipelvectomy. It may provide reasonable functional results and have some advantages such as lowering the risk of an infected implant compared with other reconstructions because no foreign implants are used. Hip transposition is generally managed with prolonged bed rest or immobilization postoperatively to stabilize the soft tissue surrounding the remaining femur. Because enabling patients to be mobile while the soft tissues heal might be advantageous, we reviewed our experience with an external fixation for this procedure. QUESTIONS/PURPOSES: (1) Does temporary external fixation facilitate postoperative physiotherapy in patients who undergo hip transposition arthroplasty? (2) What functional Musculoskeletal Tumor Society (MSTS) scores were achieved at short term in a small series of patients treated with hip transposition and temporary external fixation? (3) What were the complications of using external fixation in a small series of patients who received it for malignant tumors? METHODS: Between 2008 and 2012, we treated seven patients (three men and four women; median age, 37 years; age range, 18-53 years) with acetabular resection for malignant bone tumors; all were managed with a hip transposition, initially stabilized using external fixation. No other types of procedures were used for this indication in this period. Minimum followup in this retrospective study was 45 months, except for one patient who died at 18 months (range of followup duration, 18-90 months; median followup, 57 months), and no patients were lost to followup. The pins for external fixation were inserted into the affected side of the femur and the healthy contralateral ilium. External fixation was removed 6 weeks postoperatively and weightbearing was started at that time. Preoperative chemotherapy was administrated in four patients, but postoperative chemotherapy was delayed since it was given after external fixation removal in three patients. The postoperative rehabilitation course and functional results were assessed by chart review, functional results were determined using MSTS scores, tallied by physiotherapists who were not part of the surgical team, and complications were ascertained through chart review. Major complications were defined as complications that were treated with additional operations, such as deep infection, or ones that could cause severe postoperative dysfunction, such as nerve injury. RESULTS: With temporary external fixation, standing next to a bed was achieved in median 7 days (range, 6-9 days) postoperatively, transferring to a wheel chair in median 8 days (range, 6-28 days), and gait training using parallel bars in median 15 days (range, 7-48 days). At most recent followup, three patients could walk without a crutch or cane, three could walk with a cane, and one could walk with a crutch. The median MSTS score at most recent followup (median, 57 months) was 63%. Two patients had complications that resulted in reoperations; one had a wound dehiscence, and one had an abdominal herniation that gradually developed, and which was reconstructed using polypropylene mesh 2 years after pelvic resection. Two patients had nerve palsies that recovered by the end of the first year. All patients had pin tract infections that resolved with nonsurgical approaches. CONCLUSIONS: Hip transposition with temporary external fixation can stabilize the bone soft tissue after pelvic resection. Although we did not have a comparison group of patients, we believe that external fixation facilitates early postoperative physiotherapy and rehabilitation and provides good functional results without major surgical complications. Because it delays the resumption of chemotherapy, more patients with longer followup are needed to determine whether this will be associated with poorer oncologic results. LEVEL OF EVIDENCE: Level IV, therapeutic study.

DOI： 10.1097/CORR.0000000000000764

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A disintegrin and metalloproteinase 12 (ADAM12) is known to be involved in chondrocyte proliferation and maturation; however, the mechanisms are not fully understood. In this study, expression and localization of ADAM12 during chondrocyte differentiation were examined in the mouse growth plate by immunohistochemistry. Adam12 expression during ATDC5 chondrogenic differentiation was examined by real-time PCR and compared with the expression pattern of type X collagen. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system was used to generate Adam12-knockout (KO) ATDC5 cells. Adam12-KO and Adam12 overexpressing cells were used for analyses of ADAM12 expression with or without TGF-β1 stimulation. ADAM12 was identified predominantly in chondrocytes of the proliferative zone in mouse growth plates by immunohistochemistry. Adam12 was upregulated prior to Col10a1 during chondrogenic differentiation in wild-type ATDC5 cells. In Adam12-KO ATDC5 cells, following initiation of chondrogenic differentiation, we observed a reduction in Igf-1 expression along with an upregulation of hypertrophy-associated Runx2, Col10a1, and type X collagen protein expressions. In ATDC5 wild-type cells, stimulation with TGF-β1 upregulated the expressions of Adam12 and Igf-1 and downregulated the expression of Runx2. In contrast, in Adam12-KO ATDC5 cells, these TGF-β1-induced changes were suppressed. Adam12 overexpression resulted in an upregulation of Igf-1 and downregulation of Runx2 expression in ATDC5 cells. The findings suggest that ADAM12 has important role in the regulation of chondrocyte differentiation, potentially by regulation of TGF-β1-dependent signaling and that targeting of ADAM12 may have a role in management of abnormal chondrocyte differentiation.

DOI： 10.1007/s00223-019-00549-6

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BACKGROUND: Although osteoid osteomas have traditionally been treated by surgical excision, radiofrequency ablation (RFA) has gained favor as a less invasive procedure. However, RFA is contraindicated for osteoid osteomas close to the skin or crucial neurovascular structures, and is not covered by national health insurance in Japan. The aim of the present study was to evaluate the efficacy of surgical excision of osteoid osteomas using intraoperative navigation. METHODS: We performed a retrospective review of five patients with osteoid osteoma who underwent a mini-open excision using O-arm/Stealth navigation at our institution. The osteoid osteomas were excised using a cannulated cutter or curetted out with the assistance of navigation. RESULTS: Complete excision was achieved in all patients, which was confirmed by pathological examination. The mean skin incision was 2.1 cm (range, 1.5 to 3.0 cm) and the mean duration required for setup three-dimensional image was 15 min (range, 12 to 20 min). Although the mean visual analog scale score was 7 (range, 4 to 8) before surgery, all patients experienced relief from their characteristic pain immediately after surgery, with the mean scores of 2.2 (range, 1 to 3) and 0 at 2 days and 4 weeks after surgery, respectively. There was no intra-operative complication related to the navigation and no recurrence was observed during the mean follow-up period of 25 months (range, 13 to 33 months). CONCLUSIONS: Mini-open excision using intraoperative O-arm/Stealth navigation is a safe and accurate procedure for patients with osteoid osteoma, which could cover the limitation of RFA.

DOI： 10.1016/j.jos.2018.09.017

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DOI： 10.1016/j.jos.2016.12.011

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INTRODUCTION: Medial meniscus posterior root tear (MMPRT) can occur in middle-aged patients who have a posteromedial painful popping during light activities. MMPRTs are more common in patients with increased age, female gender, sedentary lifestyle, obesity, and varus knee alignment. However, injury mechanisms of minor traumatic MMPRTs are still unclear. We hypothesized that high flexion activities are the major cause of MMPRTs. The aim of this study was to clarify injury patterns of MMPRTs. MATERIALS AND METHODS: One hundred patients were diagnosed having MMPRTs after posteromedial painful popping episodes. Details of posteromedial painful popping episode, situation of injury, and position of injured leg were obtained from the patients by careful interviews. Injury patterns were divided into 8 groups: descending knee motion, walking, squatting, standing up action, falling down, twisting, light exercise, and minor automobile accident. RESULTS: A descending knee motion was the most common cause of MMPRTs (38%) followed by a walking injury pattern (18%) and a squatting action related to high flexion activities of the knee (13%). The other injury patterns were less than 10%. DISCUSSION: Descending knee motions associated with descending stairs, step, and downhill slope are the most common injury pattern of MMPRTs. High flexion activities of the knee are not the greatest cause of MMPRTs. Our results suggest that the descending action with a low knee flexion angle may trigger minor traumatic MMPRTs. LEVEL OF EVIDENCE: IV, retrospective cohort study.

DOI： 10.1016/j.otsr.2018.10.001

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A fibula graft is one of the most common orthopedic procedures for reconstruction of a bone defect, and some complications related to persistent defects of the fibula have been reported previously. We believe that regeneration of the fibula may be critical for postoperative function and prevention of complications. This report describes a 9-year-old female with Ewing sarcoma of the pelvis who was treated with the double-barrel fibula grafts for pelvic bone defect following tumor resection. The defect after fibular resection was filled with unidirectional porous hydroxyapatite (UDPHAp) implants. A plain radiograph revealed new bone formation and a callus-like structure at one month after surgery and bony union between each UDPHAp implant 5 months after surgery. Resorption of implanted UDPHAp was identified, and partial remodeling of the bone marrow cavity could be seen 1 year 2 months after surgery. A radiograph at final follow-up (5 years 10 months after surgery) demonstrated almost complete absorption of the implanted UDPHAp and clear formation of the cortex and bone marrow in the resected part of the fibula. The patient is able to walk well without any walking supports and to take part in sports activities.

DOI： 10.1155/2019/9024643

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Language：English   Publisher：WILEY  

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BACKGROUND: Although emerging evidence has suggested that computer-assisted navigation allows surgeons to plan the optimal level of resection without compromising the surgical margins, the precise accuracy of the procedures has been unclear. The aim of this study was to investigate the accuracy and safety of the musculoskeletal tumor resection using O-arm/Stealth intraoperative navigation assistance. METHODS: A retrospective study of six patients with bone and soft tissue tumors who underwent surgical resection using O-arm/Stealth navigation system was performed. The histological diagnosis was osteosarcoma, metastatic bone tumor, leiomyosarcoma, undifferentiated sarcoma, and synovial sarcoma, respectively. Tumor resection was performed according to planned osteotomy planes determined on O-arm/Stealth three-dimensional intraoperative images. The resection accuracy, length of time for the procedures, surgical margins, and perioperative complications were evaluated. RESULTS: The distances between the entry and exit points for the planned and actual cuts were 1.5 ± 0.3 mm and 2.3 ± 0.3 mm, respectively, and the mean discrepancy of the osteotomy angle was 2.8 ± 1.2°. The mean length of time required for navigation was 14 min. A histological examination revealed clear margins in all patients. There were no complications related to navigation, and no patients developed local recurrence during a mean follow-up of 30.6 months. CONCLUSIONS: The O-arm/Stealth intraoperative CT navigation system provides safe and accurate osteotomy in musculoskeletal tumor resections. However, surgeons should keep in mind and be careful of minimal errors during osteotomy, which are around 2 mm from the planned line.

DOI： 10.1016/j.jos.2018.06.012

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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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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：English   Publisher：WILEY  

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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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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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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Oncolytic virotherapy has recently emerged as a promising strategy for inducing tumor-specific cell death. Adenoviruses are widely and frequently used in oncolytic virotherapy. The mechanism of oncolytic adenovirus-mediated tumor suppression involves virus-induced activation of the autophagic machinery in tumor cells. Autophagy is a cytoprotective process that produces energy via lysosomal degradation of intracellular components as a physiologic response to various stresses, including hypoxia, nutrient deprivation, and disruption of growth signaling. However, infection with oncolytic adenoviruses induces autophagy and subsequent death of tumor cells rather than enhancing their survival. In this review, we summarize the beneficial role of autophagy in oncolytic adenoviral therapy, including the roles of infection, replication, and cell lysis. Numerous factors are involved in the promotion and inhibition of oncolytic adenovirus-mediated autophagy. Furthermore, recent evidence has shown that oncolytic adenoviruses induce autophagy-related immunogenic cell death (ICD), which enhances the antitumor immune response by inducing the activation of danger signal molecules and thus represents a novel cancer immunotherapy. Understanding the precise role of oncolytic adenovirus-induced autophagy and ICD could enhance the therapeutic potential of oncolytic adenoviral therapy for treating various cancers.

DOI： 10.3390/ijms18071479

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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

PubMed

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

The objective was to investigate the levels of TWIST1 in normal and OA cartilage and examine its role in regulating gene expression in chondrocytes. Human cartilage tissues and chondrocytes were obtained at autopsy from normal knee joints and from OA-affected joints at the time of total knee arthroplasty. TWIST1 expression was increased in human OA knee cartilage compared to normal knee cartilage. TWIST1 induced matrix metalloproteinase 3 (MMP3) expression without direct binding to MMP3 promoter and increased the 5-hydroxymethylcytosine (5hmC) level at the MMP3 promoter. The effect of TWIST1 on expression of TET family (TET1, 2 and 3) was measured in stable TWIST1 transfected TC28 cells, and TET1 expression was up-regulated. TWIST1 dependent upregulation of Mmp3 expression was suppressed in Tet triple KO fibroblast derived from mouse ES cells. Increased TWIST1 expression is a feature of OA-affected cartilage. We identified a novel mechanism of catabolic reaction where TWIST1 up-regulates MMP3 expression by enriching 5hmC levels at the MMP3 promoter via TET1 induction. These findings implicate TWIST1 as an important factor regulating OA related gene expression. Clarifying epigenetic mechanisms of 5hmC induced by TWIST1 is a critical molecule to understanding OA pathogenesis.

DOI： 10.1038/srep42990

Web of Science

PubMed

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

Osteosarcoma is a rare disease diagnosed as malignant bone tumor. It is generally refractory to chemotherapy, which contributes to its poor prognosis. The reversal of chemoresistance is a major clinical challenge to improve the prognostic outcome of osteosarcoma patients. We developed a tumor-specific replication-competent oncolytic adenovirus, OBP-301 (telomelysin) and assessed its synergistic effects with chemotherapeutic agents (cisplatin and doxorubicin) using human osteosarcoma cell lines and a xenograft tumor model. The molecular mechanism underlying the chemosensitizing effect of OBP-301 was evaluated in aspects of apoptosis induction. OBP-301 inhibits anti-apoptotic myeloid cell leukemia 1 (MCL1) expression, which in turn leads to chemosensitization in human osteosarcoma cells. The siRNA-mediated knockdown of MCL1 expression sensitized human osteosarcoma cells to common chemotherapeutic agents. We also found that upregulation of microRNA-29 targeting MCL1 via virally induced transcriptional factor E2F-1 activation was critical for the enhancement of chemotherapy-induced apoptosis in osteosarcoma cells. Telomerase-specific oncolytic adenovirus synergistically suppressed the viability of human osteosarcoma cells in combination with chemotherapeutic agents. The combination treatment also significantly inhibited tumor growth, as compared to monotherapy, in an osteosarcoma xenograft tumor model. Our data suggest that replicative virus-mediated tumor-specific MCL1 ablation may be a promising strategy to attenuate chemoresistance in osteosarcoma patients.

DOI： 10.1038/srep28953

PubMed

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Background: The surgical management of soft tissue sarcoma (STS) in elderly patients has only been addressed in a few studies. The objective of the current study was to assess surgical outcomes in patients with STS aged 70 years and older and the association of older age with the survival after complete resection.
Methods: A retrospective analysis was conducted in 158 elderly patients with localized STS who visited 11 institutions participating in Japanese Musculoskeletal Oncology Group between 1995 and 2006 and were treated by surgical resection. Univariate and multivariate analyses were performed to identify prognostic factors.
Results: Median follow-up period was 38 months. Histologically high-grade tumors were detected in 71% of the patients. Wide resection with adequate margins was performed in 66% of the cases. Systemic chemotherapy was performed in only 5 patients. Univariate analysis identified histological grade and gender as statistically significant prognostic factors for sarcoma-specific survival. Multivariate analysis did not identify significant prognostic factors for sarcoma-specific survival, although high grade sarcoma emerged as a potentially significant prognostic factor (P = 0.050). Local recurrence was detected in 19% of the patients. Multivariate analysis of local recurrence-free survival showed that tumor site and surgical margins were statistically significant prognostic factors.
Conclusions: Older age was not identified as a prognostic factor for sarcoma-specific survival, which is not consistent with the findings of previous studies showing that older age was associated with decreased sarcoma-specific survival. Complete resection should be indicated and can lead to optimal treatment outcome for properly selected elderly patients. (C) 2013 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.ejso.2013.09.004

Web of Science

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

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC CANCER RESEARCH  

Tumor suppressor p53 is a multifunctional transcription factor that regulates diverse cell fates, including apoptosis and autophagy in tumor biology. p53 overexpression enhances the antitumor activity of oncolytic adenoviruses; however, the molecular mechanism of this occurrence remains unclear. We previously developed a tumor-specific replication-competent oncolytic adenovirus, OBP-301, that kills human osteosarcoma cells, but some human osteosarcoma cells were OBP-301-resistant. In this study, we investigated the antitumor activity of a p53-expressing oncolytic adenovirus, OBP-702, and the molecular mechanism of the p53-mediated cell death pathway in OBP-301-resistant human osteosarcoma cells. The cytopathic activity of OBP-702 was examined in OBP-301-sensitive (U2OS and HOS) and OBP-301-resistant (SaOS-2 and MNNG/HOS) human osteosarcoma cells. The molecular mechanism in the OBP-702-mediated induction of two cell death pathways, apoptosis and autophagy, was investigated in OBP-301-resistant osteosarcoma cells. The antitumor effect of OBP-702 was further assessed using an orthotopic OBP-301-resistant MNNG/HOS osteosarcoma xenograft tumor model. OBP-702 suppressed the viability of OBP-301-sensitive and -resistant osteosarcoma cells more efficiently than OBP-301 or a replication-deficient p53-expressing adenovirus (Ad-p53). OBP-702 induced more profound apoptosis and autophagy when compared with OBP-301 or Ad-p53. E1A-mediated miR-93/106b upregulation induced p21 suppression, leading to p53-mediated apoptosis and autophagy in OBP-702-infected cells. p53 overexpression enhanced adenovirus-mediated autophagy through activation of damage-regulated autophagy modulator (DRAM). Moreover, OBP-702 suppressed tumor growth in an orthotopic OBP-301-resistant MNNG/HOS xenograft tumor model. These results suggest that OBP-702-mediated p53 transactivation is a promising antitumor strategy to induce dual apoptotic and autophagic cell death pathways via regulation of miRNA and DRAM in human osteosarcoma cells. Mol Cancer Ther; 12(3); 314-25. (C)2012 AACR.

DOI： 10.1158/1535-7163.MCT-12-0869

Web of Science

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

Adenovirus serotype 5 (Ad5) is frequently used as an effective vector for induction of therapeutic transgenes in cancer gene therapy or of tumor cell lysis in oncolytic virotherapy. Ad5 can infect target cells through binding with the coxsackie and adenovirus receptor (CAR). Thus, the infectious ability of Ad5-based vectors depends on the CAR expression level in target cells. There are conventional methods to evaluate the CAR expression level in human target cells, including flow cytometry, western blotting and immunohistochemistry. Here, we show a simple system for detection and assessment of functional CAR expression in human tumor cells, using the green fluorescent protein (GFP)-expressing telomerase-specific replication-competent adenovirus OBP-401. OBP-401 infection induced detectable GFP expression in CAR-expressing tumor cells, but not in CAR-negative tumor cells, nor in CAR-positive normal fibroblasts, 24 h after infection. OBP-401-mediated GFP expression was significantly associated with CAR expression in tumor cells. OBP-401 infection detected tumor cells with low CAR expression more efficiently than conventional methods. OBP-401 also distinguished CAR-positive tumor tissues from CAR-negative tumor and normal tissues in biopsy samples. These results suggest that GFP-expressing telomerase-specific replication-competent adenovirus is a very potent diagnostic tool for assessment of functional CAR expression in tumor cells for Ad5-based antitumor therapy. Gene Therapy (2013) 20, 112-118; doi:10.1038/gt.2011.213; published online 12 January 2012

DOI： 10.1038/gt.2011.213

Web of Science

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

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Language：Japanese   Publisher：(一社)日本骨折治療学会  

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Language：Japanese   Publisher：(一社)日本骨折治療学会  

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Language：Japanese   Publisher：日本創外固定・骨延長学会  

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Language：Japanese   Publisher：(一社)日本骨折治療学会  

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

PURPOSE: Tumor-specific replication-selective oncolytic virotherapy is a promising antitumor therapy for induction of cell death in tumor cells but not of normal cells. We previously developed an oncolytic adenovirus, OBP-301, that kills human epithelial malignant cells in a telomerase-dependent manner. Recent evidence suggests that nonepithelial malignant cells, which have low telomerase activity, maintain telomere length through alternative lengthening of telomeres (ALT). However, it remains unclear whether OBP-301 is cytopathic for nonepithelial malignant cells. Here, we evaluated the antitumor effect of OBP-301 on human bone and soft tissue sarcoma cells. EXPERIMENTAL DESIGN: The cytopathic activity of OBP-301, coxsackie and adenovirus receptor (CAR) expression, and telomerase activity were examined in 10 bone (OST, U2OS, HOS, HuO9, MNNG/HOS, SaOS-2, NOS-2, NOS-10, NDCS-1, and OUMS-27) and in 4 soft tissue (CCS, NMS-2, SYO-1, and NMFH-1) sarcoma cell lines. OBP-301 antitumor effects were assessed using orthotopic tumor xenograft models. The fiber-modified OBP-301 (termed OBP-405) was used to confirm an antitumor effect on OBP-301-resistant sarcomas. RESULTS: OBP-301 was cytopathic for 12 sarcoma cell lines but not for the non-CAR-expressing OUMS-27 and NMFH-1 cells. Sensitivity to OBP-301 was dependent on CAR expression and not on telomerase activity. ALT-type sarcomas were also sensitive to OBP-301 because of upregulation of human telomerase reverse transcriptase (hTERT) mRNA following virus infection. Intratumoral injection of OBP-301 significantly suppressed the growth of OST and SYO-1 tumors. Furthermore, fiber-modified OBP-405 showed antitumor effects on OBP-301-resistant OUMS-27 and NMFH-1 cells. CONCLUSIONS: A telomerase-specific oncolytic adenovirus is a promising antitumor reagent for the treatment of bone and soft tissue sarcomas.

DOI： 10.1158/1078-0432.CCR-10-2066

PubMed

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Language：Japanese   Publisher：(一社)日本人工関節学会  

54歳女。変形性股関節症で、10年前に右股関節に対しセメントTHAを施行し、今回、左股関節に対しTHAを施行した。Cup挿入にはnavigationを使用し、Stemは術前CTプランニングと同サイズをnavigation非使用で術中骨折等の合併症なく挿入した。術後2日で荷重歩行を開始し、術後1週のCTで骨折などは認めず経過良好であったが、術後2週で2mmのsubsidenceを認めた。荷重制限は行わず、術後3週でT字杖一本歩行で自宅退院し経過観察していたところ、徐々に骨萎縮が進行し、術後1年では著明な跛行およびX線上約4mmのsubsidenceと大腿骨の膨化を認めた。再置換術は希望されず、更に術後2年では約2cmのsubsidenceが生じ、術後2年6ヵ月にはステム遠位部での骨形成がみられた。術後2年以降、subsidenceの進行は認めていない。

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Language：Japanese   Publisher：(一社)日本骨折治療学会  

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

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：The Chugoku-Shikoku Orthopaedic Association  

DOI： 10.11360/jcsoa.34.237

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Language：Japanese   Publisher：The Chugoku-Shikoku Orthopaedic Association  

DOI： 10.11360/jcsoa.34.273

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Language：Japanese   Publisher：The Chugoku-Shikoku Orthopaedic Association  

DOI： 10.11360/jcsoa.34.233

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Language：Japanese   Publisher：The Chugoku-Shikoku Orthopaedic Association  

DOI： 10.11360/jcsoa.34.213

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Language：Japanese   Publisher：THE CENTRAL JAPAN ASSOCIATION OF ORTHOPAEDIC SURGERY AND TRAUMATOLOGY  

DOI： 10.11359/chubu.2021.799

CiNii Article

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00831&link_issn=&doc_id=20220113030029&doc_link_id=10.11359%2Fchubu.2021.799&url=https%3A%2F%2Fdoi.org%2F10.11359%2Fchubu.2021.799&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：Japanese   Publisher：(一社)日本関節病学会  

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

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

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Language：Japanese   Publisher：THE CENTRAL JAPAN ASSOCIATION OF ORTHOPAEDIC SURGERY AND TRAUMATOLOGY  

DOI： 10.11359/chubu.2021.707

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00831&link_issn=&doc_id=20211201120051&doc_link_id=10.11359%2Fchubu.2021.707&url=https%3A%2F%2Fdoi.org%2F10.11359%2Fchubu.2021.707&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

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

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：日本運動器科学会  

J-GLOBAL

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：(一社)日本移植学会  

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Publisher：南江堂  

DOI： 10.15106/j_seikei72_140

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Language：Japanese   Publisher：(株)東京医学社  

DOI： 10.24479/j00645.2021085583

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Publisher：メジカルビュー社  

DOI： 10.18885/jjs.0000000479

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

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

J-GLOBAL

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

J-GLOBAL

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)   Publisher：(株)日本臨床社  

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)   Publisher：(株)日本臨床社  

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Language：English   Publishing type：Research paper, summary (national, other academic conference)   Publisher：(一社)日本癌学会  

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Language：Japanese   Publishing type：Research paper, summary (national, other academic conference)   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Publisher：南江堂  

DOI： 10.15106/j_seikei71_786

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Publisher：(株)メジカルビュー社  

DOI： 10.18885/j00282.2020041696

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Language：English   Publisher：(一社)日本癌治療学会  

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

J-GLOBAL

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

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：English   Publisher：(一社)日本癌学会  

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J-GLOBAL

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Language：Japanese   Publisher：先端医学社  

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Other Link： https://search.jamas.or.jp/link/ui/2020037329

Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：日本運動器科学会  

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Language：Japanese   Publisher：日本運動器科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

J-GLOBAL

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

J-GLOBAL

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：日本がん免疫学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：日本運動器科学会  

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Publisher：(株)メジカルビュー社  

DOI： 10.18885/j00282.2018192551

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY  

Web of Science

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：The Japanese Association of Rehabilitation Medicine  

DOI： 10.2490/jjrmc.54.209

CiNii Article

CiNii Books

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Other Link： http://id.ndl.go.jp/bib/028088878

Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(株)東京医学社  

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

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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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

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

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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DOI： 10.18888/j00767.2016321722

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Other Link： https://search.jamas.or.jp/link/ui/2016321722

Language：Japanese   Publisher：(一社)日本骨・関節感染症学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2016-4677

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2015-1794

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(一社)中部日本整形外科災害外科学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2014-342

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2014-725

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

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

J-GLOBAL

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：西日本整形・災害外科学会  

小児大腿骨骨幹部骨折は小児の全骨折の1.4～1.7％と言われており比較的まれな外傷である．治療法は保存的，外科的治療があるが，合併症の観点からみると定まった治療法がないのが現状である．今回我々は自験例を振り返り文献的考察を加え検討したので報告する．対象は4～16歳の7症例，女児2例・男児5例であり，平均観察期間は1.8年であった．保存療法は4歳と10歳の女児2症例，髄内釘は10歳～16歳の4症例，プレート固定は13歳の1症例であった．髄内釘を使用した症例では10歳を除き骨端線閉鎖しかけている患児であった．10歳の髄内釘症例に対してrigid interlocking nailを使用した．その理由は高度な肥満を認めるうえに広範性発達障害があり免荷は困難と考えたためである．プレート固定の症例では合併症なく治癒したが，抜釘時にはbone over growthによる抜釘困難と抜釘後のプレート接触面の皮質の菲薄化を認めた．保存療法を行った10歳女児については機能的合併症は認めないものの4ヶ月と長期の入院を必要とした．小児大腿骨骨幹部骨折の治療においては年齢とともに変化する骨頭への血流支配，自家矯正能力が大きく関与しておりこのことを確実に理解し治療を行っていかなければならない．

DOI： 10.5035/nishiseisai.63.170

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Language：Japanese   Publisher：Okayama Medical Association  

DOI： 10.4044/joma.126.89

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Other Link： http://id.ndl.go.jp/bib/025753178

Language：Japanese   Publisher：THE CENTRAL JAPAN ASSOCIATION OF ORTHOPAEDIC SURGERY AND TRAUMATOLOGY  

DOI： 10.11359/chubu.2014.1295

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2013-3320

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2013-3316

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Language：Japanese   Publisher：日本創外固定・骨延長学会  

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Other Link： https://search.jamas.or.jp/link/ui/2013217235

Language：Japanese   Publisher：西日本整形・災害外科学会  

内側型変形性膝関節症（内側型OA）や，特発性大腿骨内顆骨壊死（OCN）に対して，保存的治療で改善しない症例においては，一般的には単顆人工膝関節置換術（UKA）や高位脛骨骨切術（HTO）などの適応がある．今回我々はそれらの適応があると考えられた患者のうちで，侵襲の高い手術の同意が得られなかったためArthroscopic debridementを施行した5症例（内側型OA2例：OCN3例 全例女性，平均年齢65.3歳 47～76歳）について検討したので報告する．

DOI： 10.5035/nishiseisai.62.469

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Language：Japanese  

DOI： 10.4044/joma.124.105

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Language：Japanese   Publisher：THE CENTRAL JAPAN ASSOCIATION OF ORTHOPAEDIC SURGERY AND TRAUMATOLOGY  

DOI： 10.11359/chubu.2012.1167

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Language：English   Publisher：日本癌学会  

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Language：Japanese   Publisher：(一社)日本骨折治療学会  

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Language：Japanese   Publisher：THE CENTRAL JAPAN ASSOCIATION OF ORTHOPAEDIC SURGERY AND TRAUMATOLOGY  

DOI： 10.11359/chubu.2011.387

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Language：Japanese  

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Language：Japanese   Publisher：THE CENTRAL JAPAN ASSOCIATION OF ORTHOPAEDIC SURGERY AND TRAUMATOLOGY  

DOI： 10.11359/chubu.2010.447

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Language：Japanese   Publisher：The Chugoku-Shikoku Orthopaedic Association  

We report the clinical outcome of surgical treatment for distal radius fracture using external fixation. During the period 2004-2007, 15 patients (5 men and 10 women) with a mean age of 58.0 years (range, 39-75 years) were enrolled in this study. The average follow-up period was 2 years 6 months (range: 3 months to 4 years 7 months).<br>All of the fractures were of the unstable type. X-ray evaluation was performed with ulnar plus variance (UV), volar tilt (VT) and radial inclination (RI). The clinical outcome was evaluated in terms of the Cooney score and Saito's point system. The postoperative VT and RI were markedly improved in comparison with the preoperative values. However, UV shortening deformity gradually regressed to the preoperative state. Clincal evaluation was excellent or good at 56.3% in terms of the Cooney score, and 100% by Saito's point system. Almost all of the patients expressed satisfaction, but the Cooney score was not always good. We consider that external fixation is useful not only for cases of open fracture or marked soft tissue swelling around the wrist joint, but also for severe fracture at the joint surface, and that it is also effective when used with a locking plate, depending on the circumstances.

DOI： 10.11360/jcsoa.21.307

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Presentation type：Symposium, workshop panel (nominated)  

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Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Presentation type：Symposium, workshop panel (nominated)  

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Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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