The present study evaluated the anti-cancer activity of histone deacetylase (HDAC)-inhibiting CKD-581 in multiple myeloma (MM) and its pharmacological mechanisms. CKD-581 potently inhibited a broad spectrum of HDAC isozymes. It concentration-dependently inhibited proliferation of hematologic cancer cells including MM (MM.1S and RPMI8226) and T cell lymphoma (HH and MJ). It increased the expression of the dishevelled binding antagonist of β-catenin 3 (DACT3) in T cell lymphoma and MM cells, and decreased the expression of c-Myc and β-catenin in MM cells. Additionally, it enhanced phosphorylated p53, p21, cleaved caspase-3 and the subG1 population, and reversely, downregulated cyclin D1, CDK4 and the anti-apoptotic BCL-2 family. Finally, administration of CKD-581 exerted a significant anti-cancer activity in MM.1S-implanted xenografts. Overall, CKD-581 shows anticancer activity via inhibition of the Wnt/β-catenin signaling pathway in hematologic malignancies. This finding is evidence of the therapeutic potential and rationale of CKD-581 for treatment of MM.

BACKGROUND AND PURPOSE: Elucidating the factors that predict the quality of life (QOL) in stroke patients is important. However, the residual sensory symptoms that are common in stroke patients have not usually been included as factors that influence the QOL. The purpose of the present study was to elucidate the factors that predict the QOL of chronic-stage patients with special attention to residual sensory symptoms. METHODS: We examined 214 patients who had experienced a first-time stroke during the subacute (i.e., approximately 3 months poststroke) stage; 151 patients from this group were followed up by telephone interview during the chronic (i.e., approximately 3 years poststroke) stage. Physical disabilities, including motor dysfunction, sensory symptoms that included central poststroke pain (CPSP, described using a standardized questionnaire with a visual analogue scale), activities of daily living (ADL, measured by the Barthel index score), as well as the presence of depression (using the DSM IV criteria), were assessed during both the subacute and chronic stages. Economic and job statuses during the chronic stage were also assessed. QOL ratings were determined by the World Health Organization QOL scale. RESULTS: The following factors at 3 months poststroke were related to low QOL at 3 years poststroke: dependency in ADL, motor dysfunction, depression, and CPSP. At 3 years poststroke, dependency in ADL, depression, CPSP, poor economic status, and unemployment were all factors that were related to low QOL. Multiple regression analysis showed that dependency in ADL (19%), presence of CPSP (12%), and poor economic status (10%) were important explanatory factors for overall QOL. In the analysis of QOL subdomains, the most important explanatory factors were CPSP for both physical and psychological domains, dependency in ADL for both independence and social-relationships domains, economic status for the environmental domain, and female sex for the spiritual domain. CONCLUSIONS: We conclude that dependency in ADL, depression, low socioeconomic status, and the presence of CPSP either at 3 months or 3 years poststroke are factors that are related to a low QOL at 3 years poststroke. The recognition of these factors may allow strategies to be developed to improve the QOL for stroke patients.
Activities of Daily Living ; Depression ; Female ; Humans ; Interviews as Topic ; Quality of Life* ; Social Class ; Stroke ; Unemployment ; World Health Organization ; Surveys and Questionnaires

OBJECTIVES: Previous studies have been limited to the use of cross sectional data to identify the relationships between nicotine dependence and smoking. Therefore, it is difficult to determine a causal direction between the two variables. The purposes of this study were to 1) test whether nicotine dependence or average smoking was a more influential factor in smoking cessation; and 2) propose effective ways to quit smoking as determined by the causal relations identified. METHODS: This study used a panel dataset from the central computerized management systems of community-based smoking cessation programs in Korea. Data were stored from July 16, 2005 to July 15, 2008. 711,862 smokers were registered and re-registered for the programs during the period. 860 of those who were retained in the programs for three years were finally included in the dataset. To measure nicotine dependence, this study used a revised Fagerstrom Test for Nicotine Dependence. To examine the relationship between nicotine dependence and average smoking, an autoregressive cross-lagged model was explored in the study. RESULTS: The results indicate that 1) nicotine dependence and average smoking were stable over time; 2) the impact of nicotine dependence on average smoking was significant and vice versa; and 3) the impact of average smoking on nicotine dependence is greater than the impact of nicotine dependence on average smoking. CONCLUSIONS: These results support the existing data obtained from previous research. Collectively, reducing the amount of smoking in order to decrease nicotine dependence is important for evidence-based policy making for smoking cessation.
Community Health Centers ; Health Policy ; Korea ; Nicotine ; Policy Making ; Smoke ; Smoking ; Smoking Cessation ; Tobacco Use Disorder

OBJECTIVES: Previous studies have been limited to the use of cross sectional data to identify the relationships between nicotine dependence and smoking. Therefore, it is difficult to determine a causal direction between the two variables. The purposes of this study were to 1) test whether nicotine dependence or average smoking was a more influential factor in smoking cessation; and 2) propose effective ways to quit smoking as determined by the causal relations identified. METHODS: This study used a panel dataset from the central computerized management systems of community-based smoking cessation programs in Korea. Data were stored from July 16, 2005 to July 15, 2008. 711,862 smokers were registered and re-registered for the programs during the period. 860 of those who were retained in the programs for three years were finally included in the dataset. To measure nicotine dependence, this study used a revised Fagerstrom Test for Nicotine Dependence. To examine the relationship between nicotine dependence and average smoking, an autoregressive cross-lagged model was explored in the study. RESULTS: The results indicate that 1) nicotine dependence and average smoking were stable over time; 2) the impact of nicotine dependence on average smoking was significant and vice versa; and 3) the impact of average smoking on nicotine dependence is greater than the impact of nicotine dependence on average smoking. CONCLUSIONS: These results support the existing data obtained from previous research. Collectively, reducing the amount of smoking in order to decrease nicotine dependence is important for evidence-based policy making for smoking cessation.
Community Health Centers ; Health Policy ; Korea ; Nicotine ; Policy Making ; Smoke ; Smoking ; Smoking Cessation ; Tobacco Use Disorder

STUDY DESIGN: A randomized, controlled animal study. PURPOSE: To investigate the effectiveness of fusion and new bone formation induced by demineralized bone matrix (DBM) strips with jelly strengths. OVERVIEW OF LITERATURE: The form of the DBM can make a difference to the outcome. The effect of different jelly strengths on the ability of DBM to form new bone is not known. METHODS: Forty-eight rabbits were randomized into a control group and two experimental groups. In the control group (group 1), 1.4 g of autologous iliac crest bone was placed bilaterally. In the experimental groups, a high jelly strength DBM-hyaluronic acid (HA)-gelatin strip (group 2) and a low jelly strength DBM-HA-gelatin strip (group 3) were used. The fusion was assessed with manual manipulation and radiographs. The volume of the fusion mass was determined from computed tomographic images. RESULTS: The fusion rates as determined by manual palpation were 37.5%, 93.8% and 50.0% in group 1, group 2, and group 3, respectively (p<0.05). By radiography, the fusion rate of High jelly strength DBM strip was statistically significantly greater than that of the other alternatives (p<0.05). The mean bone volume of the fusion mass as determined by computed tomography was 2,142.2+/-318.5 mm3, 3,132.9+/-632.1 mm3, and 2,741.5+/-380.4 mm3 in group 1, group 2, and group 3, respectively (p<0.05). CONCLUSIONS: These results indicate that differences in the structural and mechanical properties of gelatin that are associated with jelly strength influenced cellular responses such as cell viability and bony tissue ingrowth, facilitating greater bone fusion around high jelly strength implants.
Animals ; Bone Matrix* ; Cell Survival ; Gelatin ; Osteogenesis ; Palpation ; Rabbits ; Radiography ; Spinal Fusion

BACKGROUND: Burden of acute stroke management is increasing according to aging population and advances in the therapeutic time window. However, reduction of resident numbers by the national policy in addition to the underlying low medical charge and reward gradually leaded to a lower rate of application to neurology department. METHODS: We conducted a nationwide survey from May 29, 2017 through July 11, 2017 to evaluate the real-world working conditions and issues of acute stroke management by stroke neurologists in Korea. Of 100 candidates of stroke professors/specialists, a total of 81 physicians participated the survey comprising 40 questionnaires. RESULTS: Stroke care physicians were suffering from heavy work load of inpatient care, outpatient clinic due to shortage of manpower for caring acute stroke. There were only three hospitals (3.7%) where neurologists independently take lead an endovascular therapy. About 43% of the participants were involving in primary duty for acute stroke management stroke, majority of whom (65.7%) were on by themselves. Participants pointed out that the biggest drawbacks were manpower shortage due to lack of residents, and numerous frequencies of primary duty. Approximately 80% of the participants forecasted a dismal future for stroke field. CONCLUSIONS: With the growing incidence of stroke, there is an emerging need for increasing number of neurologists due to contemporary grave shortage of stroke neurologists. It is necessary to investigate the effective demand forecasting for stroke neurologists for the strategy to improve an unmet quality of stroke care with the awareness and help of government.
Aging ; Ambulatory Care ; Brain Infarction ; Forecasting ; Humans ; Incidence ; Inpatients ; Korea ; Neurology ; Reward ; Stroke

BACKGROUND AND PURPOSE: Troponin, a marker of myocardial injury, frequently increases and is related with poor outcome in ischemic stroke patients. However, the long-term outcome of this elevation remains uncertain. We, therefore, investigated the prognostic significance of troponin elevation for long-term mortality, and explored factors affecting troponin elevation after ischemic stroke. METHODS: We retrospectively analyzed the medical data of stroke patients who were admitted within 24 hours of symptom onset and underwent a serum cardiac troponin I test at admission during a five-year period. Information on mortality as the outcome was obtained from the National Death Certificate system. RESULTS: A total of 1,692 patients were eligible for inclusion with 33 months of median follow-up. Troponin elevation that exceeded the 99th percentile (>0.04 ng/mL) of values was detected in 166 patients (9.8%). After adjusting for baseline characteristics, troponin elevation was associated with previous ischemic heart disease and congestive heart failure, comorbid atrial fibrillation and active cancer, and increased National Institutes of Health Stroke Scale score. Patients with troponin elevation had a high risk of overall death (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.40–2.40), including stroke-related (HR 1.71, 95% CI 1.14–2.55), cardiac-related (HR 3.17, 95% CI 1.49–6.74), and cancer-related (HR 1.98, 95% CI 1.14–3.45) death than those without troponin elevation. CONCLUSIONS: Troponin elevation in the acute stage of ischemic stroke was associated with long-term mortality, mainly due to increased stroke- and cancer-related death in the first year and cardiacrelated death in the later period.
Atrial Fibrillation ; Death Certificates ; Follow-Up Studies ; Heart Failure ; Humans ; Mortality* ; Myocardial Ischemia ; National Institutes of Health (U.S.) ; Prognosis ; Retrospective Studies ; Stroke* ; Troponin I ; Troponin*