Isoproterenol increases histone deacetylase 6 expression and cell migration by inhibiting ERK signaling via PKA and Epac pathways in human lung cancer cells

Stress conditions are correlated with tumor growth, progression and metastasis. We hypothesized that stress signals might affect tumor progression via epigenetic control of gene expression and investigated the effects of stress signals on the expression levels of histone deacetylases (HDACs) and the underlying mechanisms of these effects in lung cancer cells. Treatment with isoproterenol (ISO), an analog of the stress signal epinephrine, increased the expression of HDAC6 protein and mRNA in H1299 lung cancer cells. ISO caused the deacetylation of α-tubulin and stimulated cell migration in an HDAC6-dependent manner. HDAC6 expression was increased by treatment with selective activators of cAMP-dependent protein kinase (PKA) or exchange protein activated by cAMP (Epac). ISO activated Rap1 via Epac, and constitutively active Rap1A increased the HDAC6 level; however, the knockdown of Rap1A decreased the 8-(4-cholorophenylthio)-2′-O-methyl-cAMP-induced increase in HDAC6 expression. Both PKA and Rap1A decreased c-Raf activation to inhibit extracellular signal-regulated kinase (ERK) signaling. Inhibition of ERK caused an increase in HDAC6 expression, and constitutively active MEK1 decreased the ISO-induced HDAC6 expression. We concluded that ISO increases HDAC6 expression via a PKA/Epac/ERK-dependent pathway that stimulates the migration of lung cancer cells. This study suggests that stress signals can stimulate the migration of cancer cells by inducing HDAC6 expression in lung cancer cells.

Development of a Critical Pathway for Patients with Uterine Artery Embolization / 여성건강간호학회지

PURPOSE: The purpose of this study was to develop a Critical Pathway for Uterine Artery Embolization patients. METHOD: There were 6 steps that were taken. Step 1 was selecting a diagnosis, and Step 2 was organizing a development team consisting of 7 experts. Step 3 analyzed the medical records, and Step 4 drew up a preliminary Critical Pathway. Step 5 tested the clinical validity of the preliminary Critical Pathway, and Step 6 developed the final Critical Pathway. RESULT: The contents of the medical practices observed in the medical records were investigated in seven areas: monitoring/assessment, treatment, medication, diet, activity, consults, and education/discharge plan; and a total of 73 items was identified. The validity of the 73 items was examined by a group of specialists. 68 items were adopted, 4 items revised, 1 item removed, and 1 item was added. Using the results, a preliminary Critical Pathway was drawn up. According to the results from examining the clinical validity of the preliminary Critical Pathway with five patients for five weeks, 3 items which showed discrepancy were revised and another 3 items were added. Then, the final Critical Pathway was completed. CONCLUSION: This Critical Pathway needs to be clinically applied and continuously to measure its effects in terms of the length of stay, cost?effectiveness, and the patients' and staffs' satisfaction.