Curcumin for the Prevention of Epithelial-Mesenchymal Transition in Endoxifen-Treated MCF-7 Breast Cancer Cells

Background: Curcumin was shown to reduce epithelial-mesenchymal transition (EMT) markers in previous shortterm studies. This study was aimed to investigate the potential of curcumin in the prevention of EMT activation inMCF-7 cells induced by endoxifen. Methods: MCF-7 breast cancer cells were treated with Endoxifen 1000 nM+betaestradiol1 nM with or without curcumin (8.5μM or 17 μM). Cells treated with dimethyl sulfoxide (DMSO) 0.001%were used as negative control. After 8 weeks of continuous treatment, the cells were counted, analyzed for mRNAE-cadherin, vimentin, TGF-β expression, total reactive oxygen species (ROS) and observed for morphological changesusing confocal microscope and transmission electron microscope. Result: MCF-7 cell viability was increased inendoxifen + β-estradiol group. Cell viability was significantly decreased in curcumin 17 μM, but not in curcumin8.5 μM group. Analysis of EMT markers at week 8 indicates that there were increase in vimentin and TGF-β mRNAexpressions, while E-cadherin mRNA expressions and TGF-β1 protein concentrations were shown to decrease. Theresults showed that administration of curcumin in all the dose administered were incapable improving the expressionsof vimentin, TGF-β1 and E-cadherin. There was a decrease in ROS concentration in curcumin treated cells (8.5 μM)while in curcumin 17 μM, ROS concentration was increased. Morphological observation using confocal microscopeand TEM showed the presence of mesenchymal cells and adherens junction. Conclusion: endoxifen treatments foreight weeks resulted in upregulation of EMT markers and changes in morphology of MCF-7 breast cancer cells. Theaddition of curcumin did not prevent the activation of EMT.     

Heart transplantation in pediatric patients: twelve-year experience of the Asan Medical Center

Heart transplantation is a standard treatment for end-stage heart disease. Pediatric heart transplantation, however, is not frequently performed due to the shortage of pediatric heart donors. This is the first report of pediatric heart transplantation in Korea. Our retrospective study included 37 patients younger than 18 yr of age who underwent heart transplantation at Asan Medical Center between August 1997 and April 2009. Preoperative diagnosis was either cardiomyopathy (n = 29, 78.3%) or congenital heart disease (n = 8, 22.7%). Mean follow up period was 56.9 ± 44.6 months. There were no early death, but 7 late deaths (7/37, 18.9%) due to rejection after 11, 15, 41 months (n = 3), infection after 5, 8, 10 months (n = 3), suspicious ventricular arrhythmia after 50 months (n = 1). There was no significant risk factor for survival. There were 25 rejections (25/37, 67.6%); less than grade II occurred in 17 patients (17/25, 68%) and more than grade II occurred in 8 patients (8/25, 32%). Actuarial 1, 5, and 10 yr survival was 88.6%, 76.8%, and 76.8%. Our midterm survival of pediatric heart transplantation showed excellent results. We hope this result could be an encouraging message to do more pediatric heart transplantation in Korean society.     

The CCR5 (−2135C/T) Polymorphism may be Associated with the Development of Kawasaki Disease in Korean Children

Background  Kawasaki disease (KD) is an acute vasculitis syndrome of unknown etiology that frequently affects small to medium size arteries. C-C chemokine receptor 5 (CCR5) is a chemokine receptor that binds C-C chemokines. This study investigated the association of the CCR5 (−2135C/T) polymorphism with KD in Korean children. Methods  The study population consisted 189 Korean children with KD and 194 Korean children with congenital heart disease (CHD). CCR5 (−2135C/T) polymorphism genotypes were determined using the single-base extension method. Results  The allele frequencies of the CCR5 (−2135C/T) polymorphism differed significantly between CHD children and KD children (−2135T/T, 16.75% vs. 30.05%, aOR 2.14, 95% CI 1.31–3.51). The tested laboratory parameters differed significantly between the KD and CHD groups. The development of coronary artery aneurysm in KD patients was not associated with the CCR5 polymorphism. Conclusions  Our findings suggest that the T allele at the CCR5 (−2135C/T) polymorphism might be associated with the development of KD in Korean children but does not appear to be associated with the development of coronary artery aneurysm.     

The Differential Profiling of Ubiquitin‐Proteasome and Autophagy Systems in Different Tissues before the Onset of Huntington's Disease Models

Huntington's disease (HD) is a genetic and neurodegenerative disease, leading to motor and cognitive dysfunction in HD patients. At cellular level, this disease is caused by the accumulation of mutant huntingtin (HTT) in different cells, and finally results in the dysfunction of different cells. To clean these mutant proteins, ubiquitin‐proteasome system (UPS) and autophagy system are two critical pathways in the brain; however, little is known in other peripheral tissues. As mutant HTT affects different tissues progressively and might influence the UPS and autophagy pathways at early stages, we attempted to examine two clearance systems in HD models before the onset. Here, in vitro results showed that the accumulation of UPS signals with time was observed obviously in neuroblastoma and kidney cells, not in other cells. In HD transgenic mice, we observed the impairment of UPS, but not autophagy, over time in the cortex and striatum. In heart and muscle tissues, disturbance of autophagy was observed, whereas dysfunction of UPS was displayed in liver and lung. These results suggest that two protein clearance pathways are disturbed differentially in different tissues before the onset of HD, and enhancement of protein clearance at early stages might provide a potential stratagem to alleviate the progression of HD.     

Treatment Outcomes of Intravesical Botulinum Toxin A Injections on Patients with Interstitial Cystitis/Bladder Pain Syndrome

Botulinum toxin A (BoNT-A) is effective in reducing bladder hypersensitivity and increasing capacity through the effects of anti-inflammation in the bladder urothelium; however, studies on the treatment outcome of interstitial cystitis/bladder pain syndrome (IC/BPS) are lacking. We investigated the treatment outcome in IC/BPS patients receiving intravesical BoNT-A injections. This retrospective study included IC/BPS patients who had 100U BoNT-A intravesical injections in the past 20 years. The treatment outcomes at 6 months following the BoNT-A treatment were evaluated using the global response assessment (GRA) scale. The treatment outcomes according to the GRA scale include clinical symptoms, urodynamic parameters, cystoscopic characteristics, and urinary biomarkers, and it was these predictive factors for achieving satisfactory outcomes which were investigated. Among the 220 enrolled patients (180 women, 40 men) receiving BoNT-A injections, only 87 (40%) had significantly satisfactory treatment outcomes. The satisfactory group showed significantly larger voided volumes, and lower levels of both the urinary inflammatory protein MCP-1 and the oxidative stress biomarker 8-isoprostane in comparison to the unsatisfactory group. The IC severity and detrusor pressure are predictive factors of BoNT-A treatment outcomes. IC/BPS patients with less bladder inflammation showed satisfactory outcomes with intravesical BoNT-A injections. Patients with severe bladder inflammation might require more intravesical BoNT-A injections to achieve a satisfactory outcome.     

Selective Laser Melting of Maraging Steel Using Synchronized Three-Spot Scanning Strategies

The selective laser melting (SLM) process, a kind of metal additive manufacturing method, can produce parts with complex geometries that cannot be easily manufactured using material removal processes. With increasing industrial applications, there are still issues such as part quality and productivity that need to be resolved. In this study, maraging steel parts fabricated by synchronized three-spot scanning strategies, i.e., lateral spatial (LS) and spatial inline (SiL), are firstly presented. The LS and SiL represent the three-spot offset direction is perpendicular and parallel to the scanning direction, respectively. A laboratory SLM machine equipped with a fiber laser and three-spot module is used to fabricate the maraging steel parts with two scanning strategies, i.e., LS and SiL. The influence of these scanning strategies on the surface roughness, relative density, hardness, molten pool shapes, and microstructures are investigated. The relative density (~99.02%) and surface hardness (~34.0 HRC) are experimentally found to be higher than the SiL by the LS scanning strategy.