Cell transformation induced by epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) is a critical event in cancer initiation and progression, and understanding the underlying mechanisms is essential for the development of new therapeutic strategies. Licorice extract contains various bioactive compounds, which have been reported to have anticancer and anti-inflammatory effects. This study investigated the cancer preventive efficacy of licochalcone D (LicoD), a chalcone derivative in licorice extract, in EGF and TPA-induced transformed skin keratinocyte cells. LicoD effectively suppressed EGF-induced cell proliferation and anchorage-independent colony growth. EGF and TPA promoted the S phase of cell cycle, while LicoD treatment caused G1 phase arrest and down-regulated cyclin D1 and up-regulated p21 expression associated with the G1 phase. LicoD also induced apoptosis and increased apoptosis-related proteins such as cleaved-caspase-3, cleaved-caspase-7, and Bax (Bcl-2-associated X protein). We further investigated the effect of LicoD on the AKT signaling pathway involved in various cellular processes and found decreased p-AKT, p-GSK3β, and p-NFκB expression. Treatment with MK-2206, an AKT pharmacological inhibitor, suppressed EGF-induced cell proliferation and transformed colony growth. In conclusion, this study demonstrated the potential of LicoD as a preventive agent for skin carcinogenesis.

BACKGROUND: Early recognition of the signs and symptoms of clinical deterioration could diminish the incidence of cardiopulmonary arrest. The present study investigates outcomes with respect to cardiopulmonary arrest rates in institutions with and without rapid response systems (RRSs) and the current level of cardiopulmonary arrest rate in tertiary hospitals. METHODS: This was a retrospective study based on data from 14 tertiary hospitals. Cardiopulmonary resuscitation (CPR) rate reports were obtained from each hospital to include the number of cardiopulmonary arrest events in adult patients in the general ward, the annual adult admission statistics, and the structure of the RRS if present. RESULTS: Hospitals with RRSs showed a statistically significant reduction of the CPR rate between 2013 and 2015 (odds ratio [OR], 0.731; 95% confidence interval [CI], 0.577 to 0.927; P = 0.009). Nevertheless, CPR rates of 2013 and 2015 did not change in hospitals without RRS (OR, 0.988; 95% CI, 0.868 to 1.124; P = 0.854). National university-affiliated hospitals showed less cardiopulmonary arrest rate than private university-affiliated in 2015 (1.92 vs. 2.40; OR, 0.800; 95% CI, 0.702 to 0.912; P = 0.001). High-volume hospitals showed lower cardiopulmonary arrest rates compared with medium-volume hospitals in 2013 (1.76 vs. 2.63; OR, 0.667; 95% CI, 0.577 to 0.772; P < 0.001) and in 2015 (1.55 vs. 3.20; OR, 0.485; 95% CI, 0.428 to 0.550; P < 0.001). CONCLUSIONS: RRSs may be a feasible option to reduce the CPR rate. The discrepancy in cardiopulmonary arrest rates suggests further research should include a nationwide survey to tease out factors involved in in-hospital cardiopulmonary arrest and differences in outcomes based on hospital characteristics.
Adult ; Cardiopulmonary Resuscitation ; Heart Arrest* ; Hospitals, High-Volume ; Humans ; Incidence ; Motivation* ; Patient Safety ; Patients' Rooms ; Pilot Projects* ; Quality of Health Care ; Retrospective Studies ; Tertiary Care Centers

BACKGROUND: Early recognition of the signs and symptoms of clinical deterioration could diminish the incidence of cardiopulmonary arrest. The present study investigates outcomes with respect to cardiopulmonary arrest rates in institutions with and without rapid response systems (RRSs) and the current level of cardiopulmonary arrest rate in tertiary hospitals. METHODS: This was a retrospective study based on data from 14 tertiary hospitals. Cardiopulmonary resuscitation (CPR) rate reports were obtained from each hospital to include the number of cardiopulmonary arrest events in adult patients in the general ward, the annual adult admission statistics, and the structure of the RRS if present. RESULTS: Hospitals with RRSs showed a statistically significant reduction of the CPR rate between 2013 and 2015 (odds ratio [OR], 0.731; 95% confidence interval [CI], 0.577 to 0.927; P = 0.009). Nevertheless, CPR rates of 2013 and 2015 did not change in hospitals without RRS (OR, 0.988; 95% CI, 0.868 to 1.124; P = 0.854). National university-affiliated hospitals showed less cardiopulmonary arrest rate than private university-affiliated in 2015 (1.92 vs. 2.40; OR, 0.800; 95% CI, 0.702 to 0.912; P = 0.001). High-volume hospitals showed lower cardiopulmonary arrest rates compared with medium-volume hospitals in 2013 (1.76 vs. 2.63; OR, 0.667; 95% CI, 0.577 to 0.772; P < 0.001) and in 2015 (1.55 vs. 3.20; OR, 0.485; 95% CI, 0.428 to 0.550; P < 0.001). CONCLUSIONS: RRSs may be a feasible option to reduce the CPR rate. The discrepancy in cardiopulmonary arrest rates suggests further research should include a nationwide survey to tease out factors involved in in-hospital cardiopulmonary arrest and differences in outcomes based on hospital characteristics.
Adult ; Cardiopulmonary Resuscitation ; Heart Arrest ; Hospitals, High-Volume ; Humans ; Incidence ; Motivation ; Patient Safety ; Patients' Rooms ; Pilot Projects ; Quality of Health Care ; Retrospective Studies ; Tertiary Care Centers

PURPOSE: The use of hepatitis B core antibody (HBcAb)-positive grafts is increasing, especially where hepatitis B is endemic. However, this remains controversial because of the risk of development of de novo HBV infection. METHODS: We collected information obtained between January 2000 and December 2012 and retrospectively analyzed data on 187 HBsAg-negative donors and recipients were analyzed retrospectively. De novo HBV infection was defined as development of HBsAg positivity with or without detection of HBV DNA. RESULTS: Forty patients (21.4%) received HBcAb-positive grafts. Survival rate did not differ by donor HBcAb status (P = 0.466). De novo HBV infection occurred in five patients (12.5%) who were not treated with anti-HBV prophylaxis, and was significantly more prevalent in hepatitis B surface antibody (HBsAb)- and HBcAb-negative than HBsAb- and HBcAb-positive recipients (50% vs. 4.2%, P = 0.049). All patients except one were treated with entecavir with/without antihepatitis B immunoglobulin and four were negative in terms of HBV DNA seroconversion. No patient died. CONCLUSION: HBcAb-positive grafts are safe without survival difference. However, the risk of de novo hepatitis B virus infection was significantly increased in HBsAb- and HBcAb-negative recipients. All patients were successfully treated even after recurrence.
DNA ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis* ; Humans ; Immunoglobulins ; Liver Transplantation* ; Liver* ; Prognosis ; Recurrence ; Retrospective Studies ; Survival Rate ; Tissue Donors ; Transplants*

Angiotensin II type 1 receptor blocker (ARB), which is frequently prescribed in patients with glomerulonephritis (GN), is suggested to increase the risk of cancer. We registered 3,288 patients with renal biopsy and analyzed the relationship between the use of renin-angiotensin-aldosterone system (RAAS) blockade and the incidence of cancer or cancer mortality. After renal biopsy, cancer developed in 33 patients with an incidence rate of 1.0% (95% of CI for incidence: 0.7%-1.3%). There was no difference in the cancer incidence among the groups according to the use of angiotensin-converting enzyme inhibitors (ACEI) or ARB: 1.2% in the None (23/1960), 0.7% in the ARB-only (5/748), 0.4% in the ACEI-only (1/247), and 1.2% in the ACEI-ARB (4/333) (P = 0.487) groups. The cancer mortality was 2.1%, 0.4%, 0.0%, and 0.3% in None, ACEI-only, ARB-only, and ACEI-ARB group, respectively (P < 0.001). The risk of cancer mortality in patients with ARB was only 0.124 (0.034-0.445) compared to that of non-users of ARB by Cox's hazard proportional analysis. In conclusion, prescription of ACEI or ARB in patients with GN does not increase cancer incidence and recipients of ARB show rather lower rates of all-cause mortality and cancer mortality.
Adult ; Aged ; Angiotensin II Type 1 Receptor Blockers/*therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/*therapeutic use ; Female ; Follow-Up Studies ; Glomerulonephritis/complications/diagnosis/*drug therapy ; Humans ; Incidence ; Kidney/pathology ; Male ; Middle Aged ; Neoplasms/complications/*epidemiology/mortality ; Renin-Angiotensin System/*drug effects ; Retrospective Studies ; Risk Factors

Angiotensin II type 1 receptor blocker (ARB), which is frequently prescribed in patients with glomerulonephritis (GN), is suggested to increase the risk of cancer. We registered 3,288 patients with renal biopsy and analyzed the relationship between the use of renin-angiotensin-aldosterone system (RAAS) blockade and the incidence of cancer or cancer mortality. After renal biopsy, cancer developed in 33 patients with an incidence rate of 1.0% (95% of CI for incidence: 0.7%-1.3%). There was no difference in the cancer incidence among the groups according to the use of angiotensin-converting enzyme inhibitors (ACEI) or ARB: 1.2% in the None (23/1960), 0.7% in the ARB-only (5/748), 0.4% in the ACEI-only (1/247), and 1.2% in the ACEI-ARB (4/333) (P = 0.487) groups. The cancer mortality was 2.1%, 0.4%, 0.0%, and 0.3% in None, ACEI-only, ARB-only, and ACEI-ARB group, respectively (P < 0.001). The risk of cancer mortality in patients with ARB was only 0.124 (0.034-0.445) compared to that of non-users of ARB by Cox's hazard proportional analysis. In conclusion, prescription of ACEI or ARB in patients with GN does not increase cancer incidence and recipients of ARB show rather lower rates of all-cause mortality and cancer mortality.
Adult ; Aged ; Angiotensin II Type 1 Receptor Blockers/*therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/*therapeutic use ; Female ; Follow-Up Studies ; Glomerulonephritis/complications/diagnosis/*drug therapy ; Humans ; Incidence ; Kidney/pathology ; Male ; Middle Aged ; Neoplasms/complications/*epidemiology/mortality ; Renin-Angiotensin System/*drug effects ; Retrospective Studies ; Risk Factors

BACKGROUND: Many AML patients have received hematopoietic stem cell transplantation (HSCT) from HLA-matched unrelated donors. According to many of the previous reports, those patients could achieve long-term, disease-free survival after HSCT from multinational unrelated donors with tolerable transplant-related complications, even when there are HLA-mismatches. METHODS: We present the results of 35 unrelated hematopoietic stem cell transplantations from multiple international donor banks including the Korean (n=24), and Japan Marrow Donor Program (n=3), the Taiwan Tzu Chi Marrow Donation Registry (n=6), as well as using Caucasian donors from the National Marrow Donor Program (n=2), for the treatment of AML patients. RESULTS: The median age of patients was 36 (range: 16~53) and the median follow-up duration was 21 months (range: 5~60). Also, the median age of the donors was 28 (range: 20~53). The majority of the patients had intermediate or unfavorable cytogenetic features. The main conditioning regimen we used consisted of cyclophosphamide plus TBI (n=31) with our standard GvHD prophylaxis that contained tacrolimus plus a short course of methotrexate. Some patients (n=10) received an additional two-day course of ATG (thymoglobulin, Sangstat) in addition to the standard regimen. All the transplanted patients achieved engraftment. The incidence of acute GvHD was 42%, and that of chronic GvHD was 56%. Four (11%) patients have relapsed to date. The two-year non-relapse transplant-related mortality was 26%. The estimated probability of DFS and the event-free survival at five-years were 80% and 53%, respectively. CONCLUSION: These results suggest that multinational unrelated donors HSCT may provide a feasible option for the treatment of high-risk Korean AML patients.
Bone Marrow ; Cyclophosphamide ; Cytogenetics ; Disease-Free Survival ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Humans ; Incidence ; Japan ; Leukemia, Myeloid, Acute* ; Methotrexate ; Mortality ; Tacrolimus ; Taiwan ; Tissue Donors ; Unrelated Donors*

OBJECTIVES: Incresed gamma-glutamyltransferase (GGT) concentration has mainly been used as a biologic marker of alcohol drinking and liver diseases. However, some recent reports have suggested that serum GGT concentration may be an early biomarker of oxidative stress and associated with chronic diseases like hypertension, DM, hyperlipidemia, CHD, stroke etc. In this study, we analysed the factors associated with increased serum GGT level and evaluated the clinical application of serum GGT in predicting the risk of chronic diseases. METHODS: The data were collected from 15,546 periodic health examinations, 9,660 males and 5,886 females, done at one university hospital from 2001 to 2003. We analysed self-questionnaire, physical examination and laboratory data. Statistical analyses(t-test, ANOVA, Pearson's correlation analysis, multiple regression analysis and logistic regression analysis) were done by SPSS for windows 10.0. RESULTS: Mean serum GGT levels were quite different according to age, sex, BMI, smoking and alcohol drinking (all P-value < 0.001), but were not different by regular vitamin intake or not (P-value=0.117). There was significant correlation between serum GGT level and the variables (of age, BMI, blood pressure, Hb, fasting blood sugar, total cholesterol, AST and ALT) (all P-value < 0.001). In sex-specific multiple regression analysis, increased serum GGT level was significantly associated with age, alcohol drinking, smoking, blood pressure, fasting blood sugar and ALT in males (all P-value < 0.001), and with age, alcohol drinking, smoking, Hb, blood pressure, total cholesterol and ALT in females (all P-value < 0.05). In sex-specific logistic regression analysis, increased serum GGT level was significantly associated with risk of 'clinical abnormalities'. This risk increased about 13-fold in males and 4.6-fold in females for serum GGT level over the third quatile, compared with under the first quartile. CONCLUSIONS: Serum GGT level is increased not only by alcohol drinking or liver diseases, but also by many other factors associated with chronic diseases and behavioral factors. Thus many factors should be considered in evaluating an increase in GGT level, even when within the upper normal range. Serum GGT level may be a predictor for the early development of chronic diseases.
Alcohol Drinking ; Biological Markers ; Blood Glucose ; Blood Pressure ; Cholesterol ; Chronic Disease ; Fasting ; Female ; gamma-Glutamyltransferase* ; Humans ; Hyperlipidemias ; Hypertension ; Liver Diseases ; Logistic Models ; Male ; Oxidative Stress ; Physical Examination ; Reference Values ; Smoke ; Smoking ; Stroke ; Vitamins

BACKGROUND AND OBJECTIVES: Hyperglycemia on hospital admission is a known important risk factor in patients with acute myocardial infarction. The purpose of this study was to investigate the relation between the level of hemoglobin A1c (HbA1c) and major adverse cardiac events (MACE) in non-diabetic acute myocardial infarction patients who underwent primary percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: Of the 105 acute myocardial infarction patients who underwent primary PCI between January 2002 and December 2002, 68 non diabetic patients were analyzed. The patients were divided into two groups: group I (n=46, 58.7+/-12.5 years, 37 male) with low levels of HbA1c (<6%) and group II (n=22, 64.6+/-13.1 years, 18 male) with elevated levels of HbA1c (6% to 7%). MACE was observed during the six-month clinical follow-up. RESULTS: There were no differences in the risk factors for atherosclerosis and angiographic characteristics between the two groups. Group II had a significantly higher rate of MACE (13% vs. 36%, p=0.026) compared to Group I. Logistic regression analysis disclosed that an elevated level of HbA1c, between 6 and 7%, was a significant independent predictor of MACE. CONCLUSION: An elevated level of HbA1c is a significant prognostic factor in non-diabetic acute myocardial infarction patients after primary PCI.
Angioplasty ; Atherosclerosis ; Diabetes Mellitus ; Follow-Up Studies ; Humans ; Hyperglycemia ; Logistic Models ; Myocardial Infarction* ; Percutaneous Coronary Intervention* ; Prognosis ; Risk Factors

BACKGROUND AND OBJECTIVES: Treating coronary in-stent restenosis (ISR) has become one of the major challenges for the interventional cardiologist. The aim of this study was to determine the feasibility and safety of treating ISR with drug eluting stents (DESs), and we also wanted to determine the effect of DESs on the prevention of recurrent restenosis. SUBJECTS AND METHODS: Eighty patients (age range: 60.9+/-6.4 year-old, males:females=63:17) with 82 ISR lesions that were treated successfully with DES (sirolimus- and paclitaxel-eluting stents) were enrolled in our study. Five patients received 2 stents for a total mean of 1.1+/-0.3 stents per lesion. The major adverse cardiac events (MACEs) during hospitalization, at 30 days and at 6 months after the stenting were analyzed along with the coronary angiographic findings. RESULTS: At the time of DES implantation, the mean number of ISRs was 1.4+/-0.9, and the patterns of ISR according to the Mehran classification were IB in 9 lesions (10.5%), IC in 3 lesions (3.7%), ID in 6 lesions (7.3%), II in 19 lesions (23.2%), III in 30 lesions (36.7%), and IV in 15 lesions (18.3%). The mean stent length was 27.1+/-5.6 mm and the mean acute gain was 2.58+/-0.67 mm. No in-hospital MACE was observed. During the 30-day clinical follow-up, one patient developed acute myocardial infarction due to a subacute stent thrombosis. Forty two patients with 43 lesions underwent a 6-month follow-up coronary angiogram. The mean late loss at 6 months was 0.30+/-0.74 mm. The binary restenosis rate was 9.3% (4/43 lesion). The restenosed lesions were treated by balloon angioplasty in three lesions and by additional DES implantation in one lesion. CONCLUSION: Our results demonstrated that DES was a safe and very effective method for the treatment of ISR.
Angioplasty, Balloon ; Classification ; Coronary Disease ; Coronary Restenosis ; Drug-Eluting Stents* ; Follow-Up Studies ; Hospitalization ; Humans ; Myocardial Infarction ; Stents ; Thrombosis