Efficacy and safety of denosumab treatment in a prepubertal patient with cherubism.

Background Denosumab is an inhibitor of receptor activator of nuclear factor kappa-B ligand, which strongly suppresses osteoclasts. Cherubism is a rare autosomal dominant disorder characterized by symmetrical swelling of the jaws, in which the bone is replaced by a fibrous granuloma containing osteoclast-like giant cells. Case presentation We report the efficacy and safety of denosumab treatment in a prepubertal boy with progressive cherubism. The treatment consisting of eight subcutaneous denosumab injections (120 mg/dose) in 6 months not only suppressed the expansion of the osteolytic lesions but also dramatically ossified them. However, a transiently decreased growth rate and rebounded asymptomatic hypercalcemia were associated with the treatment. Conclusions The present case demonstrated the therapeutic potential of denosumab for treatment of cherubism, although adverse effects, especially those on childhood growth, remain obscure. Further studies are needed to establish a safe and effective protocol for denosumab treatment of children.

[Relationship between alcohol consumption and external causes of death based on the forensic autopsy cases in Yamaguchi].

We analyzed forensic autopsy cases to assess the relationship between alcohol consumption and external causes of death. We divided 605 autopsy cases which had been performed from 2000 to 2011 at our department into Alcohol group (n = 172, 28.4%) and Non-alcohol group (n = 433, 71.6%) according to whether alcohol could be detected in the deceased's blood. The individuals' sex and age, season when the death occurred, cause of death, type of death and circumstances of death were analyzed. Alcohol group had a significantly higher ratio of males and younger ages (both p < 0.05). There was no significant between-group difference regarding the seasons when the deaths occurred. Alcohol group had significantly greater rates of spinal injuries, abdominal injuries, traffic accidents, and accidental drowning. "Bicycling" was revealed as a related factor of the traffic accidents only in Alcohol group. In contrast, "accident on the expressway," "riding a motorcycle," and "a passenger in a vehicle" were related factors only in Non-alcohol group. We concluded that the factors of male gender and middle-to-senior age are responsible for the increased risk of external causes of death after alcohol consumption, and that alcohol consumption is one of the risk factors for accidental death. In Japan, drunk-driving-related accidents have shown a downward trend whereas bicycling-related accidents have shown an upward trend, and similar results were obtained in the present study. The low awareness of drinking-induced pitfalls may be responsible for drinking-related bicycle accidents.

The basic helix-loop-helix transcription factor DEC2 inhibits TGF-ß-induced tumor progression in human pancreatic cancer BxPC-3 cells.

The basic helix loop helix (bHLH) transcription factor DEC2 is associated with the regulation of apoptosis, circadian rhythm and the response to hypoxia. However, the significance of DEC2 in pancreatic cancer remains unknown. Here, we showed for the first time that DEC2 inhibits the progression of human pancreatic cancer. Human pancreatic cancer BxPC-3 cells were treated with or without transforming growth factor-ß (TGF-ß), siRNA against DEC2, or a combination of TGF-ß and DEC2 siRNA or DEC2 overexpression. The cells were analyzed by RT-PCR, real-time PCR, western blotting, immunofluorescent staining and ChIP assay. We also performed immunohistochemical analyses of DEC2 expression in surgically-resected pancreatic cancers. The expression of DEC2 was increased in TGF-ß-treated BxPC-3 cells. In the presence of TGF-ß, DEC2 overexpression decreased the migration and invasion of BxPC-3 cells. Knockdown of DEC2 by siRNA in the presence of TGF-ß significantly increased the expression and nuclear concentration of slug. We also showed that DEC2 siRNA decreased the binding of DEC2 to the E-box of the slug promoter. Immunohistochemically, little DEC2 was detected in pancreatic cancer tissues, whereas significant amounts were detected in the adjacent non-cancerous pancreatic tissues. These results indicate that DEC2 has inhibitory effects against human pancreatic cancer that involve TGF-ß and slug.