microRNAs (miRs) play an important role in tumor initiation and progression in many types of cancer, including cholangiocarcinoma (CC). miR-138 dysregulation is frequently observed in a variety of tumors. In the present study, miR-138 was found to be downregulated in CC tissues by quantitative real-time RT-PCR. Furthermore, its potential target molecule, Ras homolog gene family, member C (RhoC) protein, was found to be highly expressed in CC tissues examined by western blot analysis. Luciferase reporter assay further demonstrated that miR-138 directly targeted RhoC. We found that the introduction of miR-138 mimics to RBE and QBC939 CC cells could reduced RhoC mRNA and protein expression, and suppressed the proliferation, G1/S transition, migration and invasion of CC cells. However, transfection with a miR-138 inhibitor induced an inverse effect in CC cells. The expression of phosphorylated extracellular signal-regulated kinase (p-ERK), matrix metalloproteinase (MMP)-2 and MMP-9 decreased following transfection with miR-138, and increased following transfection with miR-138 inhibitor in CC cells. In conclusion, RhoC upregulation induced by miR-138 downregulation promotes the malignant progression of CC cells and the underlying mechanisms of this effect involve the increase in the expression of p-ERK/MMP-2/MMP-9. Consequently, miR-138/RhoC is a potential target for the clinical diagnosis and treatment of CC.
Ostericum citriodorum is a plant with a native range in China used in herbal medicine for treating angina pectoris. In this study, we investigated the vasodilatory effects of isodillapiolglycol (IDG), which is one of the main ingredients isolated from O. citriodorum ethyl acetate extract, in Sprague–Dawley rat aortic rings, and measured intracellular Ca2+ ([Ca2+]in) using a molecular fluo-3/AM probe. The results show that IDG dose-dependently relaxed endothelium-intact or -denuded aortic rings pre-contracted with noradrenaline (NE) or potassium chloride (KCl), and inhibited CaCl2-induced contraction in high K+ depolarized aortic rings. Tetraethyl ammonium chloride (a Ca2+-activated K+ channel blocker) or verapamil (an L-type Ca2+ channel blocker) significantly reduced the relaxation of IDG in aortic rings pre-contracted with NE. In vascular smooth muscle cells, IDG inhibited the increase in [Ca2+]in stimulated by KCl in Krebs solution; likewise, IDG also attenuated the increase in [Ca2+]in induced by NE or subsequent supplementation of CaCl2. These findings demonstrate that IDG relaxes aortic rings in an endothelium-independent manner by reducing [Ca2+]in, likely through inhibition of the receptor-gated Ca2+ channel and the voltage-dependent Ca2+ channel, and through opening of the Ca2+-activated K+ channel.
Introduction: Systemic treatment for metastatic breast cancer has typically been determined by the immunohistochemistry (IHC) characteristics of the primary tumor. However, recent studies have shown that the immunophenotype of distant breast cancer metastases may be different from that of the primary tumor (receptor conversion). Methods: From August 5, 2010 to November 1, 2012 atotal of 121 metastatic breast cancer tissues from different sites, bone metastases excluded, (56 liver, 37 lymph node, 20 chest wall, 7 contralateral breast, 1 abdominal nodule) were IHC stained for estrogen receptorα (ERα), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). For the 108 cases with primary tissue slides, expression was compared to the reviewed IHC of the primary tumors. This comparison is our emphasis to avoid the difference between centers. For the other 13 cases whose primary tumors can not be acquired, the primary pathology reports were taken as reference. HER2 fluorescence in situ hybridization (FISH) was used in the case of HER2 2+ results. Results: At a 10% threshold, receptor conversion as determined by IHC for ERα and PR occurred in 25.0% and 25.9% of cases, respectively. Conversion from ER+ or PR+ to ER–/PR–occurred in 14.1% of cases, and from ER–/PR– to ER+ or PR+ in 7.7%. At a 1% threshold, receptor conversion by IHC for ERα and PR occurred in 23.2% and 27.7% of cases, respectively. Conversion from ER+ or PR+ to ER–/PR–occurred in 14.1% of cases and from ER–/PR– to ER+ or PR+ 9.0%. HER2 conversion occurred in 12.1% of patients, and was mainly from negative in he primary tumor to positive in metastases.
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