The effects of histone deacetylase (HDAC) inhibitors on epithelial-mesenchymal transition (EMT) differ in various types of cancers. We investigated the EMT phenotype in four colon cancer cell lines when challenged with HDAC inhibitors trichostatin A (TSA) and valproic acid (VPA) with or without transforming growth factor-β1 (TGF-β1) treatment. Four colon cancer cell lines with different phenotypes in regards to tumorigenicity, microsatellite stability and DNA mutation were used. EMT phenotypes were assessed by the expression of E-cadherin and vimentin using western blot analysis, immunofluorescence, quantitative real-time RT-PCR following treatment with TSA (100 or 200 nM) or VPA (0.5 mM) with or without TGF-β1 (5 ng/ml) for 24 h. Biological EMT phenotypes were also evaluated by cell morphology, migration and invasion assays. TSA or VPA induced mesenchymal features in the colon carcinoma cells by a decrease in E-cadherin and an increase in vimentin expression at the mRNA and protein levels. Confocal microscopy revealed membranous attenuation or nuclear translocation of E-cadherin and enhanced expression of vimentin. These responses occurred after 6 h and increased until 24 h. Colon cancer cells changed from a round or rectangular shape to a spindle shape with increased migration and invasion ability following TSA or VPA treatment. The susceptibility to EMT changes induced by TSA or VPA was comparable in microsatellite stable (SW480 and HT29) and microsatellite unstable cells (DLD1 and HCT116). TSA or VPA induced a mesenchymal phenotype in the colon carcinoma cells and these effects were augmented in the presence of TGF-β1. HDAC inhibitors require careful caution before their application as new anticancer drugs for colon cancers.
Ceftriaxone is widely used in patients for the treatment of serious gram-negative infections. Ceftriaxone can induce some potential side effects, including neurotoxicity, however, nonconvulsive status epilepticus has rarely been reported. We report a case of acute reversible neurotoxicity associated with ceftriaxone. A 65-yr-old woman with chronic kidney disease developed altered consciousness during ceftriaxone treatment for urinary tract infection. The electroencephalogram demonstrated continuous bursts of generalized, high-voltage, 1 to 2 Hz sharp wave activity. Neurologic symptoms disappeared following withdrawal of ceftriaxone. The possibility of ceftriaxone-induced neurotoxicity should be considered in patients developing neurological impairment during ceftriaxone use, and the discontinuation of the drug could lead to complete neurological improvement.
A standardized small bowel (SB) cleansing scale is currently not available. The aim of this study was to develop an automated calculation software for SB cleansing score using deep learning. Consecutively performed capsule endoscopy cases were enrolled from three hospitals. A 5-step scoring system based on mucosal visibility was trained for deep learning in the training set. Performance of the trained software was evaluated in the validation set. Average cleansing score (1.0 to 5.0) by deep learning was compared to clinical grading (A to C) reviewed by clinicians. Cleansing scores decreased as clinical grading worsened (scores of 4.1, 3.5, and 2.9 for grades A, B, and C, respectively, P < 0.001). Adequate preparation was achieved for 91.7% of validation cases. The average cleansing score was significantly different between adequate and inadequate group (4.0 vs. 2.9, P < 0.001). ROC curve analysis revealed that a cut-off value of cleansing score at 3.25 had an AUC of 0.977. Diagnostic yields for small, hard-to-find lesions were associated with high cleansing scores (4.3 vs. 3.8, P < 0.001). We developed a novel scoring software which calculates objective, automated cleansing scores for SB preparation. The cut-off value we suggested provides a standard criterion for adequate bowel preparation as a quality indicator.
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