Giant cell tumor of bone (GCTB) is an intermediate tumor known to be locally aggressive, but rarely metastasizing. To plan a prospective study of GCTB, we performed a questionnaire survey for institutions participating in the Bone and Soft Tissue Tumor Study Group (BSTTSG) in the Japan Clinical Oncology Group (JCOG) in 2015. We reviewed 158 consecutive patients with primary GCTB treated with curettage without perioperative denosumab from 2008 to 2010 in Japan. We investigated local and distant recurrence rates after definitive curettage. We also investigated the recurrence rate after treatment with preoperative and/or postoperative denosumab with curettage in recent years. There were 40 patients treated with perioperative denosumab, and the factors affecting recurrence in them were investigated. Answers were available from 24 of 30 institutions (80.0%) participating in JCOG BSTTSG. Thirty (19.0%) and 4 (2.5%) of 158 patients developed local and distant recurrence after curettage without perioperative denosumab from 2008 to 2010, respectively. Campanacci grade and embolization before surgery were significantly associated with increasing incidence of local recurrence after curettage (p = 0.034 and p = 0.022, respectively). In patients treated with perioperative desnosumab, 120 mg denosumab was administered subcutaneously for a median 6 (2–41) and 6 (1–14) times in preoperative and postoperative settings, respectively. The recurrence rates were 6 of 21 (28.6%), 2 of 9 (22.2%), and 0 of 10 (0.0%) in the preoperative, postoperative, and both pre- and postoperative denosumab treatment groups, respectively. With all of the preoperative treatments, administration exceeding five times was significantly associated with a decreased incidence of local recurrence after curettage (p < 0.001). The recurrence rate of GCTB was still high after curettage, especially in Campanacci grade III, and improvements in the therapeutic strategy are needed in this cohort. There is a possibility that a sufficient dose of preoperative denosumab can reduce recurrence after curettage. Recently, we have started a clinical trial, JCOG1610, to investigate the efficacy of preoperative denosumab in patients who can be treated with curettage in GCTB.

A number of studies have reported that decreased mitochondrial numbers are linked with neoplastic transformation and/or tumor progression, including resistance to apoptosis. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a multi-functional transcriptional coactivator that regulates the activities of multiple nuclear receptors and transcriptional factors involved in mitochondrial biogenesis. In this study, we observed that the number of mitochondria in sarcoma tissues, such as osteosarcoma and malignant fibrous histiocytoma, is significantly lower than that in normal muscle tissue or benign tumors and that increasing the number of mitochondria by PGC-1α overexpression induces mitochondrial apoptosis in human sarcoma cell lines. The findings suggest that decreased mitochondrial numbers may contribute to musculoskeletal tumor progression and that regulation of mitochondrial numbers by PGC-1α could be a potent therapeutic tool for human malignancies.

This study aimed to investigate the association between abdominal adiposity and change in cognitive function in community-dwelling older adults. This longitudinal study included older adults aged ≥60 years without cognitive impairment who participated in the National Institute for Longevity Sciences - Longitudinal Study of Aging. Cognitive function was evaluated biennially using the Mini-Mental State Examination (MMSE) over 10 years. Waist circumference (WC) was measured at the naval level, and subcutaneous fat area (SFA) and visceral fat area (VFA) were assessed using baseline computed tomography scans. WC, SFA, and VFA areas were stratified into sex-adjusted tertiles. A linear mixed model was applied separately for men and women. This study included 873 older adults. In men, the groups with the highest levels of WC, SFA, and VFA exhibited a greater decline in MMSE score than the groups with the lowest levels (β [95% confidence interval]: WC, -0.12 [-0.23 to -0.01]; SFA, -0.13 [-0.24 to -0.02]; VFA, -0.11 [-0.22 to -0.01]). In women, the group with the highest level of WC and SFA showed a greater decline in MMSE score than the group with the lowest level (WC, -0.12 [-0.25 to -0.01]; SFA, -0.18 [-0.30 to -0.06]), but VFA was not associated with cognitive decline. Higher WC, SFA, and VFA in men and higher WC and SFA in women were identified as risk factors for cognitive decline in later life, suggesting that abdominal adiposity involved in cognitive decline may differ according to sex.

Background: Cancer stem cells (CSCs) are considered to be responsible for tumor initiation, formation, and poor prognosis of cancer patients. However, the rarity of CSCs in clinical samples makes it difficult to elucidate characteristics of CSCs, especially in osteosarcoma (OS). The aim of this study is to verify whether it is possible to generate CSC-like cells by transducing defined factors into an OS cell line.Methods: We retrovirally transduced the Octamer-binding transcription factor 3/4 (OCT3/4), Kruppel-like factor 4 (KLF4), and SRY-box transcription factor 2 (SOX2) genes into the MG-63 human OS cell line (MG-OKS). Parental and GFP-transduced MG-63 cells were used as negative control. We assessed the properties of the generated cells in vitro and in vivo. Multiple comparisons among groups were made using a one-way analysis of variance (ANOVA) followed by post hoc testing with Tukey’s procedure.Results: MG-OKS cells in vitro exhibited the significantly increased mRNA expression levels of CSC markers (CD24,CD26, andCD133), decreased cell growth, increased chemoresistance and cell migration, and enhanced sphere formation. Notably, MG-OKS cells cultured under osteogenic differentiation conditions showed strongly positive staining for both Alizarin Red S and alkaline phosphatase, indicating osteogenesis of the cells. Gene ontology analysis of microarray data revealed significant upregulation of epidermal-related genes. Tumors derived from MG-OKS cells in vivo were significantly larger than those from other cells in μCT analysis, and immunohistochemical staining showed that Ki-67, osteocalcin, and HIF-1α-positive cells were more frequently detected in the MG-OKS-derived tumors.Conclusions: In this study, we successfully generated OS CSC-like cells with significantly enhanced CSC properties following transduction of defined factors.