1.Dynamic relocalization of NHERF1 mediates chemotactic migration of ovarian cancer cells toward lysophosphatidic acid stimulation.
Yong Seok OH ; Kyun HEO ; Eung Kyun KIM ; Jin Hyeok JANG ; Sun Sik BAE ; Jong Bae PARK ; Yun Hee KIM ; Minseok SONG ; Sang Ryong KIM ; Sung Ho RYU ; In Hoo KIM ; Pann Ghill SUH
Experimental & Molecular Medicine 2017;49(7):e351-
NHERF1/EBP50 (Na⁺/H⁺ exchanger regulating factor 1; Ezrin-binding phosphoprotein of 50 kDa) organizes stable protein complexes beneath the apical membrane of polar epithelial cells. By contrast, in cancer cells without any fixed polarity, NHERF1 often localizes in the cytoplasm. The regulation of cytoplasmic NHERF1 and its role in cancer progression remain unclear. In this study, we found that, upon lysophosphatidic acid (LPA) stimulation, cytoplasmic NHERF1 rapidly translocated to the plasma membrane, and subsequently to cortical protrusion structures, of ovarian cancer cells. This movement depended on direct binding of NHERF1 to C-terminally phosphorylated ERM proteins (cpERMs). Moreover, NHERF1 depletion downregulated cpERMs and further impaired cpERM-dependent remodeling of the cell cortex, suggesting reciprocal regulation between these proteins. The LPA-induced protein complex was highly enriched in migratory pseudopodia, whose formation was impaired by overexpression of NHERF1 truncation mutants. Consistent with this, NHERF1 depletion in various types of cancer cells abolished chemotactic cell migration toward a LPA gradient. Taken together, our findings suggest that the high dynamics of cytosolic NHERF1 provide cancer cells with a means of controlling chemotactic migration. This capacity is likely to be essential for ovarian cancer progression in tumor microenvironments containing LPA.
Cell Membrane
;
Cell Movement
;
Cytoplasm
;
Cytosol
;
Epithelial Cells
;
Membranes
;
Ovarian Neoplasms*
;
Pseudopodia
;
Tumor Microenvironment
2.Fermented Pueraria Lobata extract ameliorates dextran sulfate sodium-induced colitis by reducing pro-inflammatory cytokines and recovering intestinal barrier function.
Seungho CHOI ; Jong Kyu WOO ; Yeong Su JANG ; Ju Hee KANG ; Jung Eun JANG ; Tae Hoo YI ; Sang Yong PARK ; Sun Yeou KIM ; Yeo Sung YOON ; Seung Hyun OH
Laboratory Animal Research 2016;32(3):151-159
Inflammatory bowel disease is a chronic inflammatory disorder occurring in the gastrointestinal track. However, the efficacy of current therapeutic strategies has been limited and accompanied by side effects. In order to eliminate the limitations, herbal medicines have recently been developed for treatment of IBD. Peuraria Lobata (Peuraria L.) is one of the traditional herbal medicines that have anti-inflammatory effects. Bioavailability of Peuraria L., which is rich in isoflavones, is lower than that of their fermented forms. In this study, we generated fermented Peuraria L. extracts (fPue) and investigated the role of fPue in inflammation and intestinal barrier function in vitro and in vivo. As the mice or intestinal epithelial cells were treated with DSS/fPue, mRNA expression of pro-inflammatory cytokines was reduced and the architecture and expression of tight junction proteins were recovered, compared to the DSS-treated group. In summary, fPue treatment resulted in amelioration of DSS-induced inflammation in the colon, and the disrupted intestinal barrier was recovered as the expression and architecture of tight junction proteins were retrieved. These results suggest that use of fPue could be a new therapeutic strategy for treatment of IBD.
Animals
;
Biological Availability
;
Colitis*
;
Colon
;
Cytokines*
;
Dextran Sulfate*
;
Dextrans*
;
Epithelial Cells
;
In Vitro Techniques
;
Inflammation
;
Inflammatory Bowel Diseases
;
Isoflavones
;
Mice
;
Pueraria*
;
RNA, Messenger
;
Tight Junction Proteins
3.Korean Pharmacological Treatment Guideline for Child-Adolescent Depression: The Efficacy and Choice of Antidepressant.
Hoo Rim SONG ; Young Hwa LEE ; Sujin YANG ; Ji Young LEE ; Jeong Won JANG ; Sona JEONG ; Hyunsuk JEONG ; Sun Jin JO ; Hyeon Woo YIM ; So Young LEE ; Tae Youn JUN
Korean Journal of Psychopharmacology 2014;25(4):175-185
OBJECTIVE: The purpose of this guideline was to suggest recommendations for appropriate use of antidepressants in the child-adolescent depression. The differences of efficacy among antidepressants were evaluated. METHODS: Four kinds of reliable guidelines for the treatments of child-adolescent depression had been selected, and evidences and recommendations were extracted by the executive committee under the peer review. All the process was applied to the Manual for Guideline Adaptation version 2.0 by National Evidence-based Healthcare Collaborating Agency. RESULTS: Selective serotonin reuptake inhibitor (SSRI) could be considered for the treatments of moderate to severe child-adolescent depression. Among SSRIs, fluoxetine, sertraline, and escitalopram were recommended as having antidepressant efficacy compared with placebo, while paroxetine, venlafaxine, and tricyclic antidepressant were not recommended owing to lack of evidence. Another recommendation was to use combined treatment with cognitive behavioral therapy. CONCLUSION: This guideline, which was made through former and strict process of guideline adaptation, would contribute toward improving the quality of child-adolescent depression treatment by providing useful recommendations for the choice of antidepressant.
Adolescent
;
Antidepressive Agents
;
Child
;
Citalopram
;
Cognitive Therapy
;
Delivery of Health Care
;
Depression*
;
Fluoxetine
;
Humans
;
Paroxetine
;
Peer Review
;
Serotonin
;
Sertraline
;
Venlafaxine Hydrochloride
4.Risk Factors for Failure of Early Catheter Removal After Greenlight HPS Laser Photoselective Vaporization Prostatectomy in Men With Benign Prostatic Hyperplasia.
Woong Jin BAE ; Sun Gook AHN ; Jun Ho BANG ; Jang Ho BAE ; Yong Sun CHOI ; Su Jin KIM ; Hyuk Jin CHO ; Sung Hoo HONG ; Ji Youl LEE ; Tae Kon HWANG ; Sae Woong KIM
Korean Journal of Urology 2013;54(1):31-35
PURPOSE: To assess the risk factors for developing urinary retention after removal of the urethral catheter on postoperative day 1 in benign prostatic hyperplasia patients who underwent Greenlight HPS laser photoselective vaporization prostatectomy (PVP). MATERIALS AND METHODS: The study included 427 men who underwent Greenlight HPS laser PVP between 2009 and 2012, excluding patients in whom a catheter was maintained for more than 1 day because of urethral procedures. In all patients, a voiding trial was performed on postoperative day 1; if patients were unable to urinate, the urethral catheter was replaced before hospital discharge. The patients were divided into two groups: early catheter removal (postoperative day 1) and late catheter removal (urethral catheter reinsertion). Preoperative and perioperative parameters were compared between the groups. RESULTS: Catheters were successfully removed in 378 (88.6%) patients on postoperative day 1. In 49 patients, the catheters were reinserted and removed a mean of 6.45+/-0.39 days after surgery. In a multivariate analysis, a history of diabetes was the most significant predictor (p=0.028) of failure of early catheter removal, followed by operative time (p=0.039). There were no significant differences in age, prostate volume, International Prostate Symptom Score, or urodynamic parameters between the two groups. CONCLUSIONS: It is feasible, safe, and cost-effective to remove the urethral catheter on postoperative day 1 after Greenlight HPS laser PVP, but the procedure should be done carefully in patients who have history of diabetes or an extended operative time.
Catheters
;
Humans
;
Laser Therapy
;
Male
;
Multivariate Analysis
;
Operative Time
;
Prostate
;
Prostatectomy
;
Prostatic Hyperplasia
;
Risk Factors
;
Urinary Catheterization
;
Urinary Catheters
;
Urinary Retention
;
Urodynamics
;
Volatilization
5.Influence of Intravesical Prostatic Protrusion on Preoperative Lower Urinary Tract Symptoms and Outcomes after 120 W High Performance System Laser Treatment in Men with Benign Prostatic Hyperplasia.
Jang Ho WEE ; Yong Sun CHOI ; Woong Jin BAE ; Su Jin KIM ; Hyuk Jin CHO ; Sung Hoo HONG ; Ji Youl LEE ; Sae Woong KIM
Korean Journal of Urology 2012;53(7):472-477
PURPOSE: To evaluate the efficacy of photoselective vaporization of the prostate (PVP) with the 120 W Greenlight high performance system (HPS) laser for the treatment of benign prostatic hyperplasia (BPH) with intravesical prostatic protrusion (IPP). MATERIALS AND METHODS: This study was conducted on 389 BPH patients who underwent PVP with the 120 W HPS laser from April 2009 to August 2011. The patients were divided into groups according to IPP: group I was defined as IPP of 0 to 5 mm (n=216), group II as IPP of 5 to 10 mm (n=135), and group III as IPP above 10 mm (n=38). Prostate volume, prostate-specific antigen, International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), and postvoid residual volume (PVR) were assessed and checked at postoperative 1, 3, 6, and 12 months. RESULTS: There was a significant difference in the mean prostate size in each group (p<0.05). The preoperative total IPSS score, IPSS voiding symptom score, and quality of life score were not significantly different. However, the IPSS storage symptom score was significantly different between groups 1 and 2 and group 3. IPSS scores, Qmax, and PVR at postoperative 1, 3, 6, and 12 months showed significant improvement compared with preoperative values. CONCLUSIONS: The degree of IPP can affect storage symptoms. However, there is no significant correlation between the degree of IPP and postoperative results. Also, the degree of IPP does not affect short- and long-term PVP results. Proper elimination of bladder outlet obstruction is important for symptomatic relief.
Humans
;
Indoles
;
Laser Therapy
;
Lower Urinary Tract Symptoms
;
Male
;
Prostate
;
Prostate-Specific Antigen
;
Prostatic Hyperplasia
;
Quality of Life
;
Residual Volume
;
Urinary Bladder Neck Obstruction
;
Volatilization
6.The Socioeconomic Burden of Coronary Heart Disease in Korea.
Hoo Sun CHANG ; Han Joong KIM ; Chung Mo NAM ; Seung Ji LIM ; Young Hwa JANG ; Sera KIM ; Hye Young KANG
Journal of Preventive Medicine and Public Health 2012;45(5):291-300
OBJECTIVES: We aimed to estimate the annual socioeconomic burden of coronary heart disease (CHD) in Korea in 2005, using the National Health Insurance (NHI) claims data. METHODS: A prevalence-based, top-down, cost-of-treatment method was used to assess the direct and indirect costs of CHD (International Classification of Diseases, 10th revision codes of I20-I25), angina pectoris (I20), and myocardial infarction (MI, I21-I23) from a societal perspective. RESULTS: Estimated national spending on CHD in 2005 was 2.52 billion dollar . The majority of the spending was attributable to medical costs (53.3%), followed by productivity loss due to morbidity and premature death (33.6%), transportation (8.1%), and informal caregiver costs (4.9%). While medical cost was the predominant cost attribute in treating angina (74.3% of the total cost), premature death was the largest cost attribute for patients with MI (66.9%). Annual per-capita cost of treating MI, excluding premature death cost, was 3183 dollar, which is about 2 times higher than the cost for angina (1556 dollar). CONCLUSIONS: The total insurance-covered medical cost (1.13 billion dollar) of CHD accounted for approximately 6.02% of the total annual NHI expenditure. These findings suggest that the current burden of CHD on society is tremendous and that more effective prevention strategies are required in Korea.
Adult
;
Age Factors
;
Aged
;
Aged, 80 and over
;
Angina Pectoris/economics/epidemiology
;
Coronary Disease/*economics/epidemiology
;
*Cost of Illness
;
Female
;
Health Care Costs/statistics & numerical data
;
Humans
;
Insurance, Health/statistics & numerical data
;
Male
;
Middle Aged
;
Myocardial Infarction/economics/epidemiology
;
Prevalence
;
Republic of Korea/epidemiology
;
Sex Factors
;
Socioeconomic Factors
;
Young Adult
7.Sustainability of Korean National Health Insurance.
Myoung Sheen KANG ; Hoo Sun JANG ; Minjee LEE ; Eun Cheol PARK
Journal of Korean Medical Science 2012;27(Suppl):S21-S24
Korean National Health Insurance (NHI) was established during only 12 yr from its inception (1977-1989), providing universal medical coverage to the entire nation and making a huge contribution to medical security. However, the program now faces many challenges in terms of sustainability. The low birth rates, aging population, low economic growth, and escalating demands for welfare, as well as unification issues, all add pressure to the sustainability of NHI. The old paradigm of low contribution - low benefits coverage - low NHI's fee schedule needs to be replaced by a new paradigm of proper contribution - adequate benefit coverage - fair NHI's fee schedule. This new paradigm will require reform of NHI's operating system, funding, and spending.
Health Care Reform
;
Humans
;
National Health Programs/*economics
;
Program Evaluation
;
Republic of Korea
;
Risk Factors
;
Universal Coverage/economics
8.Expression of the Transmembrane Glycoprotein CD44s Is Potentially an Independent Predictor of Recurrence in Hepatocellular Carcinoma.
Han Suk RYU ; Sun Hoo PARK ; Kyung Bun LEE ; Eun SHIN ; Ja June JANG
Gut and Liver 2011;5(2):204-209
BACKGROUND/AIMS: Cluster differentiation 44 standard isoform (CD44s) is a transmembrane glycoprotein. CD44s is a known prognostic factor in various cancers, due to its involvement in tumor cell growth, invasion and metastasis. Its prognostic role, however, is debated because it can be a positive or negative prognostic factor depending on tumor type and is still an ambiguous prognostic indicator in other cancers, especially hepatocellular carcinoma (HCC). We investigated the relationship between CD44s expression and survival in HCC patients. METHODS: A total of 260 HCC samples were collected to generate a tissue microarray. Staining of the arrays with a primary mouse CD44s monoclonal antibody was followed by evaluation of the relationship between CD44s expression and tumor differentiation. The effect of CD44s expression on patient survival was analyzed. RESULTS: CD44s protein expression correlated with histological grade (most and worst Edmondson grade) of the HCC (p=0.029 and p=0.039, respectively) and adversely affected the disease free survival period based on univariate and multivariate analyses (p=0.038 and p=0.077, respectively). CONCLUSIONS: High CD44s protein expression correlates with shorter disease free survival and poorly differentiated HCC. CD44s-targeted therapy may be efficacious for HCC treatment in the future.
Animals
;
Antigens, CD44
;
Carcinoma, Hepatocellular
;
Disease-Free Survival
;
Glycoproteins
;
Humans
;
Mice
;
Multivariate Analysis
;
Neoplasm Metastasis
;
Protein Array Analysis
;
Recurrence
9.Focal-Type Autoimmune Pancreatitis Mimicking Cholangiocarcinoma.
Young Joo JANG ; Ki Young YANG ; Sang Bum KIM ; Sun Hoo PARK ; Young AHN ; Jae Hyun YANG ; Jong Hwan LEE
Korean Journal of Medicine 2011;80(Suppl 2):S121-S125
Autoimmune pancreatitis (AIP) is a rare pancreatic disorder of autoimmune etiology. It has characteristic clinical features, such as pancreatic parenchymal swelling and irregular narrowing of the main pancreatic duct due to plasma cell infiltration. It occurs mostly in Far East Asia. Although it generally involves whole pancreatic parenchyma, some cases demonstrate focal involvement of the pancreas or adjacent organs, which are often mistaken for cancer. We report a case of AIP that was confused with cholangiocarcinoma of the distal common bile duct (CBD). The patient experienced sudden development of jaundice with vague abdominal discomfort. Abdominal computed tomography revealed a well-enhanced lesion, and positron emission tomography showed high standard uptake value at the distal CBD, indicating malignant disease. However, pathological examination by surgical excision indicated focal-type AIP. This is believed to be the first case of focal-type AIP mimicking cholangiocarcinoma.
Asia
;
Autoimmunity
;
Cholangiocarcinoma
;
Common Bile Duct
;
Far East
;
Humans
;
Jaundice
;
Pancreas
;
Pancreatic Ducts
;
Pancreatitis
;
Plasma Cells
;
Positron-Emission Tomography
10.Socioeconomic Costs of Stroke in Korea: Estimated from the Korea National Health Insurance Claims Database.
Seung ji LIM ; Han joong KIM ; Chung mo NAM ; Hoo sun CHANG ; Young Hwa JANG ; Sera KIM ; Hye Young KANG
Journal of Preventive Medicine and Public Health 2009;42(4):251-260
OBJECTIVES: To estimate the annual socioeconomic costs of stroke in Korea in 2005 from a societal perspective. METHODS: We identified those 20 years or older who had at least one national health insurance (NHI) claims record with a primary or a secondary diagnosis of stroke (ICD-10 codes: I60-I69, G45) in 2005. Direct medical costs of the stroke were measured from the NHI claims records. Direct non-medical costs were estimated as transportation costs incurred when visiting the hospitals. Indirect costs were defined as patients' and caregivers' productivity loss associated with office visits or hospitalization. Also, the costs of productivity loss due to premature death from stroke were calculated. RESULTS: A total of 882,143 stroke patients were identified with prevalence for treatment of stroke at 2.44%. The total cost for the treatment of stroke in the nation was estimated to be 3,737 billion Korean won (KRW) which included direct costs at 1,130 billion KRW and indirect costs at 2,606 billion KRW. The per-capita cost of stroke was 3 million KRW for men and 2 million KRW for women. The total national spending for hemorrhagic and ischemic stroke was 1,323 billion KRW and 1,553 billion KRW, respectively, which together consisted of 77.0% of the total cost for stroke. Costs per patient for hemorrhagic and ischemic stroke were estimated at 6 million KRW and 2 million KRW, respectively. CONCLUSIONS: Stroke is a leading public health problem in Korea in terms of the economic burden. The indirect costs were identified as the largest component of the overall cost.
Adult
;
Aged
;
Aged, 80 and over
;
Female
;
*Health Care Costs
;
*Health Expenditures
;
Humans
;
Insurance Claim Review
;
Korea
;
Male
;
Middle Aged
;
Prevalence
;
Socioeconomic Factors
;
Stroke/*economics
;
Young Adult

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