Rhabdomyosarcoma (RMS) is an aggressive pediatric cancer of musculoskeletal origin. Despite multidisciplinary approaches, such as surgical resection, irradiation, and intensive chemotherapy, adopted for its treatment, the prognosis of patients with high-risk RMS remains poor. Thus, molecularly targeted therapies are required to improve patient survival and minimize side effects. Histone deacetylases (HDACs) modify transcription by deacetylation of the lysine residues in chromatin histone tails and several non-histone proteins. HDAC inhibitors, classes of compounds targeted to various HDAC proteins, are being studied for their roles in several types of cancers in a rigorous manner. This study aimed to investigate the potential of a novel HDAC inhibitor, OBP-801, as a therapeutic agent for the treatment of RMS. We used 8 RMS cell lines in this study. Protein expression patterns, cell proliferation, cell cycle status, and apoptosis in RMS cells after OBP-801 treatment in vitro were investigated. We also studied the antitumor activity of OBP-801 in an in vivo xenograft mouse model. We observed cell cycle arrest at the M-phase and apoptosis in all RMS cell lines after exposure to pharmacological levels of OBP-801 for 24 h. Immunofluorescence staining revealed that OBP-801 may induce mitotic catastrophe via chromosome misalignment and reduced survivin expression, ultimately leading to apoptosis. Our results demonstrated that the novel HDAC inhibitor OBP-801 was an effective inhibitor of RMS cell line proliferation and may be a potent therapeutic option for RMS.

Tofacitinib suppressed mechanical stress-induced expression of ADAMTS4, ADAMTS5, and MMP13 by human chondrocytes through inhibition of the JAK/STAT and MAPK cascades.

Seronegative myasthenia gravis (MG) is a generalized form of MG that is diagnosed on the basis of clinical symptoms, electrophysiological testing, and pharmacological responses, in the absence of a seropositive status for anti-acetylcholine receptor (AChR) antibodies. Generalized MG that is seronegative for anti-AChR, anti-muscle-specific kinase (MuSK), and anti-low density lipoprotein receptor related protein 4 (Lrp4) antibodies is known as triple-seronegative MG. We here describe a case of triple-seronegative MG in an 8-year-old boy. His first symptom was dysphagia, at 3 years of age, and he subsequently developed ptosis, rhinolalia, and a waddling gait. A genetic analysis was conducted to exclude the possibility of congenital myasthenia syndrome due to the patient's resistance to steroid therapy. His condition was successfully managed with tacrolimus therapy over a 5-year follow-up period. Recently, several studies have reported the therapeutic utility of tacrolimus in juvenile seropositive MG; in contrast, a few reports have described tacrolimus treatment in cases of seronegative MG. Our findings suggest that tacrolimus therapy is a safe and effective option for the treatment of juvenile seronegative MG.

Swyer-James syndrome is a rare syndrome that occurs as a result of repeated bronchiolitis and pneumonitis in childhood. Most cases are asymptomatic, and subsequent diagnosis may not occur until adulthood. We present the case of a 7-year-old female with Swyer-James syndrome, which was initially diagnosed and treated as asthma. The patient developed respiratory distress and atelectasis which were treated with biphasic cuirass ventilation. This case suggests that Swyer-James syndrome should be a concern in patients with chronic cough and wheezing, and highlights the importance of taking a careful history and appropriate radiological investigations for diagnosis. Once Swyer-James syndrome is diagnosed, prophylaxis and appropriate management of respiratory infections becomes important.

We investigated the expression and localization of the receptor activator nuclear factor κB ligand (RANKL) in cartilage from patients with rheumatoid arthritis (RA) of relevance to cartilage degeneration. We also examined the role of exogenous lymphotoxin (LT)-α on RANKL expression in human chondrocytes and its effect on in vitro osteoclast differentiation. Cartilage and synovial fluid samples were obtained from 45 patients undergoing total joint replacement surgery or joint puncture, including 24 patients with osteoarthritis (OA) and 21 patients with RA. RANKL expression in articular cartilage was examined by immunohistochemistry. LT-α concentrations in synovial fluid were measured using an enzyme-linked immunosorbent assay (ELISA). Normal human chondrocytes were stimulated with LT-α, and the relative mRNA levels of RANKL, osteoprotegerin (OPG), matrix metalloproteinase-9, and vascular endothelial growth factor were examined by real-time polymerase chain reaction. Soluble RANKL protein in culture media was measured using ELISA, and membrane-bound RANKL protein in cells was examined by western blotting. Co-cultures of human chondrocytes with peripheral blood mononuclear cells (PBMCs) were stimulated with macrophage-colony stimulating factor and LT-α, and osteoclast differentiation was evaluated by staining for tartrate-resistant acid phosphatase. LT-α concentrations were higher in RA synovial fluid than in OA samples. The population of RANKL-positive chondrocytes of RA cartilage was higher than that of OA cartilage, and correlated with cartilage degeneration. Stimulation of cultured human chondrocytes by LT-α increased RANKL expression, the RANKL/OPG ratio, and angiogenic factors. Membrane-bound RANKL in chondrocytes was up-regulated after stimulation of LT-α, whereas soluble RANKL in culture medium did not increase. Co-cultures of human chondrocytes and PBMCs demonstrated that LT-α stimulated human chondrocytes to produce RANKL and induced osteoclastic differentiation of PBMCs. RANKL produced by chondrocytes may contribute to cartilage destruction during RA and LT-α could promote the expression of RANKL in human chondrocytes.