Multipotent DFCs can be induced to differentiate towards osteoblasts, adipocytes or chondrocytes in vitro. Runx2 over-expression up-regulated expression levels of osteoblast/cementoblast-related genes and in vitro enhanced osteogenic differentiation of DFCs. In addition, mutant Runx2-induced changes in DFCs were more prominent than those induced by full-length Runx2.

Background and Objective The majority of experiments show that tumor necrosis factor‐alpha (TNF‐α) inhibits osteogenic differentiation of mesenchymal stem cells and pre‐osteoblasts by activated nuclear factor‐kappaB (NF‐κB) signaling. However, the underlying mechanisms by which NF‐κB signaling inhibits osteogenic differentiation are not fully understood. The aim of the present study was to investigate whether EphB4 signaling inhibition mediates the effects of TNF‐α‐activated NF‐κB signaling on osteogenic differentiation of pre‐osteoblasts. Material and Methods Murine MC3T3‐E1 pre‐osteoblasts were treated with 10 ng/mL of TNF‐α. NF‐κB inhibitor, pyrrolidine dithiocarbamate, was used to achieve NF‐κB signaling inhibition. EphB4 signaling was activated using ephrinB2‐fc. The mRNA expressions of runt related transcription factor 2 (Runx2), bone sialoprotein (BSP) and EphB4 were determined using reverse transcription‐polymerase chain reaction. The protein levels of Runx2, BSP, Col Ia1, osteopontin, EphB4, p‐NF‐κB p65 and NF‐κB p65 were evaluated using western blot assays. Alkaline phosphatase (ALP) activity in MC3T3‐E1 cells was evaluated by ALP activity kit, and mineral nodule formation was evaluated by Alizarin Red S staining. Results TNF‐α inhibited EphB4 expression, while it suppressed Runx2, BSP expression from gene and protein levels as well as ALP activity and mineral nodule formation in MC3T3‐E1 cells. Activation of EphB4 signaling by ephrinB2‐fc promoted osteogenic differentiation of MC3T3‐E1 cells, whereas TNF‐α impaired the osteogenic differentiation enhanced by ephrinB2‐fc. Pyrrolidine dithiocarbamate blocked the activation of NF‐κB signaling induced by TNF‐α, while it prevented the downregulation of Runx2, BSP and EphB4, induced by TNF‐α. Conclusion TNF‐α inhibits osteogenic differentiation of pre‐osteoblasts by downregulation of EphB4 signaling via activated NF‐κB signaling pathway.

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Intrathecal n ¼ 2), and ventriculo-peritoneal (VP) shunt (n ¼ 1), were performed. The median overall survival time from diagnosis for all patients was 56 days. Number (single vs multiple) of BM (p ¼ 0.03), tumor location of GC (P ¼ 0.05), and treatment method (p ¼ 0.004) were significant factors in univariate analysis, and treatment method was a significant factor in multivariate analysis. The outcome of the aggressive treatment methods (77.5 day) was better than of the conservative approach (19.5 day). Conclusions: Aggressive treatment to control BM and LMC may have a positive effect on prognosis. VP shunt for LMC may be beneficial in reducing cerebrospinal pressure in an emergency. Tumor resection had only done for patients with solitaly metastasis. WBRT has a late adverse effect, and SRS provides excellent results in select patients with a few BM. Lastly, it is believed that molecularly-targeted therapies such as trastuzumab, cannot penetrate the blood-brain barrier, but newer drugs like ramucirumab are expected to be superior in this regard for BM of hematogenous metastasis.Legal entity responsible for the study: N/A Funding: None Disclosure: All authors have declared no conflicts of interest.220P Retrospective analysis of paclitaxel and ramucirumab for unresectable gastric cancer. Hypertension during 1st cycle has possibility of predictive factor