Ethacrynic acid suppresses B7-H4 expression involved in epithelial-mesenchymal transition of lung adenocarcinoma cells via inhibiting STAT3 pathway.

Lung cancer is characterized by high incidence and mortality. 90% of cancer deaths are caused by metastases. The epithelial-mesenchymal transition (EMT) process in cancer cells is a prerequisite for the metastatic process. Ethacrynic acid (ECA) is a loop diuretic that inhibits the EMT process in lung cancer cells. EMT has been related to the tumour immunemicroenvironment. However, the effect of ECA on immune checkpoint molecules in the context of cancer has not been fully identified. In the present study, we found that sphingosylphosphorylcholine (SPC) and TGF-ß1, awell-known EMT inducer, induced the expression of B7-H4 in lung cancer cells. We also investigated the involvement of B7-H4 in the SPC-induced EMT process. Knockdown of B7-H4 suppressed SPC-induced EMT, while B7-H4 overexpression enhanced EMT of lung cancer cells. ECA inhibited SPC/TGF-ß1-induced B7-H4 expression via suppression of STAT3 activation. Moreover, ECA inhibits the colonization of mice lung by tail vein-injected LLC1 cells. ECA-treated mice increased the CD4-positive T cells in lung tumour tissues. In summary, these results suggested that ECA inhibits B7-H4 expression via STAT3 inhibition, leading to SPC/TGF-ß1-induced EMT. Therefore, ECA might be an immune oncological drug for B7-H4-positive cancer, especially lung cancer.

Analysis of injury mechanism of the elderly and non-elderly groups in minor motor vehicle accidents.

OBJECTIVE: The purpose of this study is to investigate the injury patterns of noncatastrophic accidents by individual age groups. METHODS: Data were collected from the Korean In-Depth Accident Study database based on actual accident investigation. The noncatastrophic criteria were classified according to U.S. experts from the Centers for Disease Control and Prevention's recommendations for field triage guidelines of high-risk automobile crash criteria by vehicle intrusions more than 12 in. on occupant sites (including the roof) and more than 18 in. on any site. The Abbreviated Injury Scale (AIS) was used to determine injury patterns for each body region. Severely injured patients were classified as Maximum Abbreviated Injury Scale (MAIS) 3 or higher. RESULTS: In this study, the most significant injury regions were the head and neck, extremities, and thorax. In addition, the incidence of severe injury among elderly patients was nearly 1.6 times higher than that of non-elderly patients. According to age group, injured body regions among the elderly were the thorax, head and neck, and extremities, in that order. For the non-elderly groups, these were head and neck, extremities, and thorax. Severe injury rates were slightly different for the elderly group (head and neck, abdomen) and non-elderly group (thorax, head and neck). CONCLUSIONS: In both age groups, the rate of severe injury is proportional to an increase in crush extent zone. Front airbag deployment may have a relatively significant relationship to severe injuries.