Prostaglandin E2 plays a role in an array of pathophysiological responses, including inflammation, carcinogenesis and so on. Prostaglandin E2 is synthesized from arachidonic acid by the enzymes cyclooxygenase and prostaglandin E synthase. In some pathological conditions, the isozymes cyclooxygenase-2 and microsomal prostaglandin E synthase-1 are transiently induced, leading to prostaglandin E2 overproduction. The present study showed that Dioscorea japonica extract suppresses mRNA expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in human non-small-cell lung carcinoma A549 cells in a dose-dependent manner. The suppressive effects of Dioscorea japonica extract on the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 were confirmed by Western blotting, cyclooxygenase activity and prostaglandin E2 production. Dioscorea japonica extract induced the translocation of nuclear factor-κB from the nucleus to the cytosol and inhibited the activity of the cyclooxygenase-2 promoter. Furthermore Dioscorea japonica extract suppressed the expression of the anti-apoptotic factor B-cell chronic lymphocytic leukemia/lymphoma 2 and enhanced apoptotic terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive intensity in A549 cells. These results suggest that Dioscorea japonica extract suppresses the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1, with the regulation of the transcriptional activity of cyclooxygenase-2, and induces apoptosis in cancer cells. Thus, Dioscorea japonica may contribute to the prevention of prostaglandin E2-mediated pathophysiological responses such as carcinogenesis and inflammation.

Rheumatoid arthritis (RA), one of the most common articular diseases, is characterized by chronic inflammation, hyperproliferation of synovial cells, and bone destruction. CD81, which belongs to a family of cell-surface proteins (tetraspanin), is known to be up-regulated in RA synoviocytes. Recently, we showed the therapeutic effect of using small interfering RNA in targeting CD81 (CD81 siRNA) for RA. Here we show how tumor necrosis factor-alpha (TNF-α) can induce the expression of synoviolin, which is decreased by the addition of CD81 siRNA in SW982 cells. In addition, CD81 siRNA decreases the expression of TNF-α in SW982 cells, suggesting that TNF-α stimulates the expression of synoviolin via CD81. Furthermore, knock down of CD81 by the addition of CD81 siRNA decreases the expression of TNF-α, and TNF-α-induces expression of synoviolin in direct and indirect ways. These results in SW982 cells might explain the therapeutic effect of CD81 siRNA in animal models.

BackgroundUnintended exposure to antitumor agents from an oral medicine may place healthcare workers and patients taking medicine at risk. In this study, the exposure to blister pack by CP (cyclophosphamide) and appropriate preventive procedures were examined.FindingsCP detected inside the blister pack of the tested seven lots by LC-MS/MS ranged from 8.2 to 199.6 ng. Raman imaging clearly showed that CP ingredient was completely covered by the tablet coating layer and had not leached out of the tablet. In addition, the amount of CP detected inside the vials was suppressed under the lower detection limit until day 28, and only 6.0 ng was detected only at day 56.ConclusionsVarious amounts of CP were contaminated to not only the inside of the blister pack but also the outside. This contamination may be caused not only by the manufacturing environment but also by the CP oral tablets themselves through volatilization of CP. Refrigerated storage of CP oral tablets may protect healthcare workers and patients from contact with CP.Electronic supplementary materialThe online version of this article (doi:10.1186/s40780-015-0020-9) contains supplementary material, which is available to authorized users.

We recently reported that various amounts of cyclophosphamide (CP) had contaminated both the inside and outside of the blister pack, and refrigerated storage of CP oral tablets can protect healthcare workers and patients from contact CP exposure. However, the contamination from a non-volatile agent, fluorouracil (FU), and its preventive procedures are not elucidated. Here we showed high levels of FU were detected from inside the blister pack. Raman imaging showed that the FU ingredient was not attached to the surface of the tablet coating layer and had not leached out of the tablet. In addition, the amount of FU detected inside the blister pack had no significant change by physical loading including shaking and heating. Thus, the FU contamination could be because of the manufacturing environment rather than the FU oral tablets themselves. We suggest that the pharmacists should instruct the patients to administer or handle tablets and capsules containing antitumor agents without direct hand contact. In addition, pharmacists should provide information about the contamination state and effective decontamination procedures for antitumor agents.