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-β (TGF-β), siRNA against DEC2, or a combination of TGF-β 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-β-treated BxPC-3 cells. In the presence of TGF-β, DEC2 overexpression decreased the migration and invasion of BxPC-3 cells. Knockdown of DEC2 by siRNA in the presence of TGF-β 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-β and slug.

BackgroundDenosumab 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 presentationWe 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.ConclusionsThe 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.

Low-rank approximation by QR decomposition with pivoting (pivoted QR) is known to be less accurate than singular value decomposition (SVD); however, the calculation amount is smaller than that of SVD. The least upper bound of the ratio of the truncation error, defined by $$\Vert A-BC\Vert _2$$ ‖ A - B C ‖ 2 , using pivoted QR to that using SVD is proved to be $$\sqrt{\frac{4^k-1}{3}(n-k)+1}$$ 4 k - 1 3 ( n - k ) + 1 for $$A\in {\mathbb {R}}^{m\times n}$$ A ∈ R m × n $$(m\ge n)$$ ( m ≥ n ) , approximated as a product of $$B\in {\mathbb {R}}^{m\times k}$$ B ∈ R m × k and $$C\in {\mathbb {R}}^{k\times n}$$ C ∈ R k × n in this study.