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Park S.H.,Gangnam Medical Center | Song J.-Y.,Korea University | Kim Y.-K.,Korea University | Heo J.H.,CHA Medical University | And 7 more authors.
International Journal of Oncology | Year: 2014

Fascin1 (FSCN1) involved in cell motility and filopodia assembly plays important roles in biological processes such as cancer invasion and metastasis of multiple epithelial tumors. High-grade serous ovarian carcinoma (HGSOC) is aggressive and metastatic by acquiring an invasive phenotype and this step requires remodeling of the actin cytoskeleton. Thus, the present study aimed to investigate the expression of fascin1 in HGSOC tissues as well as its clinical significance such as prognostic predictors and its utility of therapeutic target. Fascin1 and β-catenin were evaluated using immunohistochemistry on a tissue microarray of 79 HGSOC. Small interfering RNA (siRNA) approach was used to knock down fascin1 expression in ovarian cancer cell lines to determine whether fascin1 contributes to tumor cell proliferation, migration and invasion. Fascin1 expression levels were determined by western blot analysis after siRNA transfection using two human ovarian cancer cell lines (SKOV3 and OVCAR3). Fascin1 overexpression was significantly correlated with lymph node involvement, distance metastasis and high International Federation of Gynecology and Obstetrics (FIGO) stage (III/IV) (P<0.05). A Kaplan-Meier analysis showed that the fascin1 expression group was significantly associated with poor overall survival (P=0.010). We showed that inactivation of fascin1 by siRNA transfection led to a drop in cell viability, and significantly decreased tumor cell proliferation, migration and invasiveness compared to untransfected cells. We found that fascin1 expression is a potential poor marker of prognosis for patients with HGSOC and knockdown of fascin1 suppresses ovarian cancer cell proliferation and migration, this could be applied for therapeutic targets in ovarian cancer treatment.

Cho Y.,Gangnam Medical Center | Kim J.O.,Institute for Clinical Research | Lee J.H.,Bundang Medical Center | Park H.M.,Institute for Clinical Research | And 6 more authors.
PLoS ONE | Year: 2015

Stroke is the second leading cause of death in the world and in South Korea. Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vascular diseases, including stroke and SBI. Folate and vitamin B12 are important regulators of homocysteine metabolism. Reduced folate carrier (RFC), a bidirectional anion exchanger, mediates folate delivery to a variety of cells. We selected three known RFC-1 polymorphisms (-43C>T, 80A>G, 696T>C) and investigated their relationship to cerebral infarction in the Korean population. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze associations between the three RFC-1 polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. The frequencies of the RFC-1 -43TT, 80GG, and 696CC genotypes differed significantly between the stroke and control groups. The RFC-1 80A>G substitution was also associated with small artery occlusion and SBI. In a gene-environment analysis, the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms in the ischemic stroke group had combined effects with all environmental factors. In summary, we found that the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms may be risk factors for ischemic stroke. © 2015 Cho et al.

Oh B.,Cancer Research Institute | Kim T.Y.,Cancer Research Institute | Min H.J.,Cancer Research Institute | Kang M.S.,Gangnam Medical Center | And 4 more authors.
Anti-Cancer Drugs | Year: 2013

The antiproliferative effect of simvastatin on tumor cells has been speculated to be by intracellular signal inhibition through 3-hydroxy-3- methylglutaryl acetyl coenzyme A reductase. We examined the killing effect of simvastatin on imatinib-sensitive and resistant chronic myelogenous leukemia (CML) cells (three kinds of CML cell lines representative of each hematopoietic lineage: K562, KCL22, and LAMA84) and T315I and E255K site-directed mutant cells (Ba/F3). The in-vivo effect of simvastatin was determined in K562-xenografted nude mice. Cotreatment with imatinib and simvastatin in imatinib-resistant CML cells showed a synergistic killing effect in K562-R, KCL22-R, LAMA84-R, and E255K mutant cells, but only an additive effect in the T315I mutant cell, although a single treatment of simvastatin strongly inhibited T315I mutant cells. Mechanisms of killing were an induction of apoptosis and cell cycle arrest, through inhibition of tyrosine phosphorylation, and activated STAT5 and STAT3. Simvastatin suppressed the growth of K562-transplanted tumors, and cotreatment with imatinib was more effective in reducing tumor size. Simvastatin also killed primary CD34 cells from patients with CML more efficiently, compared with CD34 CML cells. Our study shows a synergic effect of imatinib and simvastatin both in imatinib-sensitive and imatinib-resistant cells, but more effective synergism in resistant cells. On the basis of these findings, we suggest that a combination of simvastatin and imatinib may be a potential candidate for the treatment of imatinib-resistant CML. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Park H.J.,CHA Medical University | Kim S.H.,CHA Medical University | Jung Y.W.,CHA Medical University | Shim S.S.,CHA Medical University | And 7 more authors.
BMC Pregnancy and Childbirth | Year: 2014

Background: Our primary objective was to establish a cutoff value for the soluble fms-like tyrosine kinase 1(sFlt-1)/placental growth factor (PlGF) ratio measured using the Elecsys assay to predict late-onset preeclampsia in low-risk pregnancies. Our secondary objective was to evaluate the ability of combination models using Elecsys data, second trimester uterine artery (UtA) Doppler ultrasonography measurements, and the serum fetoplacental protein levels used for Down's syndrome screening, to predict preeclampsia.Methods: This prospective cohort study included 262 pregnant women with a low risk of preeclampsia. Plasma levels of pregnancy-associated plasma protein-A (PAPP-A) and serum levels of alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and inhibin-A were measured, and sFlt-1/PlGF ratios were calculated. All women underwent UtA Doppler ultrasonography at 20 to 24 weeks of gestation.Results: Eight of the 262 women (3.0%) developed late-onset preeclampsia. Receiver operating characteristic curve analysis showed that the third trimester sFlt-1/PlGF ratio yielded the best detection rate (DR) for preeclampsia at a fixed false-positive rate (FPR) of 10%, followed by the second trimester sFlt-1/PlGF ratio, sFlt-1 level, and PlGF level. Binary logistic regression analysis was used to determine the five best combination models for early detection of late-onset preeclampsia. The combination of the PAPP-A level and the second trimester sFlt-1/PlGF ratio yielded a DR of 87.5% at a fixed FPR of 5%, the combination of second and third trimester sFlt-1/PlGF ratios yielded a DR of 87.5% at a fixed FPR of 10%, the combination of body mass index and the second trimester sFlt-1 level yielded a DR of 87.5% at a fixed FPR of 10%, the combination of the PAPP-A and inhibin-A levels yielded a DR of 50% at a fixed FPR of 10%, and the combination of the PAPP-A level and the third trimester sFlt-1/PlGF ratio yielded a DR of 62.5% at a fixed FPR of 10%.Conclusions: The combination of the PAPP-A level and the second trimester sFlt-1/PlGF ratio, and the combination of the second trimester sFlt-1 level with body mass index, were better predictors of late-onset preeclampsia than any individual marker. © 2014 Park et al.; licensee BioMed Central Ltd.

Lee H.-J.,Seoul National University | Ahn H.S.,Seoul National University | Choi Y.B.,Asan Medical Center | Han S.-M.,Gangnam Medical Center | And 12 more authors.
Obesity Surgery | Year: 2016

A survey to evaluate the current status of bariatric and metabolic operations in Korea was conducted. Data from 5467 cases (32 hospitals) were collected. The annual numbers of bariatric and metabolic operations increased each year, from 139 in 2003 to 1686 in 2013. Adjustable gastric band (AGB, 67.2 %) was the most common operation, followed by sleeve gastrectomy (SG, 14.2 %), and Roux-en-Y gastric bypass (RYGB, 12.7 %). Mean patient age and body mass index (BMI) were 35.4 years and 35.9 kg/m2, respectively. In-hospital morbidity and mortality rates were 6 % (114/2305) and 0.25 % (5/2176), respectively. In Korea, AGB was the most common operation because of the availability and activity of specialized bariatric clinics. These national survey results established a baseline for future data collection. © 2015, The Author(s).

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