SCI 발표논문

전체 4,588편

21282016

제1저자 조유리 · 교신저자 윤정환

, , , , , ,
Fucoidan-induced ID-1 suppression inhibits the in vitro and in vivo invasion of hepatocellular carcinoma cells.
Biomed Pharmacother. 2016;83:607-616.

Abstract
Hepatocellular carcinoma (HCC) is a fast growing tumor associated with a high tendency for vascular invasion and distant metastasis. Recently, we reported that fucoidan displays inhibitory effect on proliferation and invasion of HCC cells. In this study, we investigated the anti-metastatic effect of fucoidan on HCC cells and the key signal that modulates metastasis. The anti-metastatic effect of fucoidan was evaluated in vitro using an invasion assay with human HCC cells (Huh-7, SNU-761, and SNU-3085) under both normoxic (20% O₂ and 5% CO₂, at 37°C) and hypoxic (1% O_2, 5% CO₂, and 94% N_2, at 37°C) conditions. Complementary DNA (cDNA) microarray analysis was performed to find the molecule which is significantly suppressed by fucoidan. In vivo study using a distant metastasis model by injecting SNU-761 cells into spleen via portal vein was performed to confirm the inhibitory effect by small interfering RNA (siRNA) transfection. Immunoblot analyses were used to investigate the signaling pathway. Fucoidan significantly suppressed the invasion of human HCC cells (Huh-7, SNU-761, and SNU-3085). Using cDNA microarray analysis, we found the molecule, ID-1, which was significantly suppressed by fucoidan treatment. Downregulation of ID-1 by siRNA significantly decreased invasion of HCC cells, both in vitro and in vivo (both P<0.05) in a NDRG-1/CAP43-dependent manner. In immunoblot assay, downregulation of ID-1 by siRNA decreased the expressions of epithelial-mesenchymal transition markers including CK19, vimentin, MMP2, and fibronectin. Immunofluorescence study also revealed that actin rearrangement was inhibited when ID-1 was down-regulated in HCC cells. Interestingly, in SNU-761 cells, the ID-1 expressions under hypoxic conditions were lower as compared to those under normoxic conditions. Under hypoxic conditions, HIF-1α up-regulated NDRG-1/CAP43, while HIF-2α down-regulated ID-1, which might be a compensatory phenomenon against hypoxia-induced HCC invasion. In conclusion, NDRG-1/CAP43-dependent down-regulation of ID-1 suppressed HCC invasion both in vitro and in vivo, which was modulated by fucoidan treatment. Moreover, the compensatory down-regulation of ID-1 against hypoxia-induced HCC invasion was observed. ID-1 is a novel therapeutic target for the treatment of metastatic HCC.
PubMed IF 7.5 소화기내과
21272016

제1저자 박진주,윤창환 · 교신저자 채인호, 최동주

, , , , , ,
Reduction of Ischemic Time for Transferred STEMI Patients Using a Smartphone Social Network System.
J Am Coll Cardiol. 2016;68(13):1490-1492.

PubMed IF 22.3 순환기내과
21262016

제1저자 최윤정 · 교신저자 김나영

, , , , , , , , , , , , ,
PMK-S005 Alleviates Age-Related Gastric Acid Secretion, Inflammation, and Oxidative Status in the Rat Stomach.
Gut Liver. 2016;10(5):749-56.

Abstract
BACKGROUND/AIMS The aim of this study was to evaluate the effect of the synthetic S-allyl-L-cysteine (SAC) PMK-S005 on gastric acid secretion, inflammation, and antioxidant enzymes in aging rats.
METHODS The rats were divided into four groups at 31 weeks of age and were continuously fed a diet containing a vehicle control, PMK-S005 (5 or 10 mg/kg), or lansoprazole (5 mg/kg). Gastric acid secretion and connective tissue thickness of the lamina propria were evaluated at 74 weeks and 2 years of age. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and COX-2 levels were measured by using enzyme-linked immunosorbent assays (ELISAs) or Western blot assays. Levels of antioxidant enzymes, including heme oxyganase 1 (HO-1) and
NAD(P)H quinone oxidoreductase 1 (NQO-1), were also measured.
RESULTS As the rats aged, gastric acid secretion significantly decreased, and the connective tissue of the lamina propria increased. However, 74-week-old rats in the PMK-S005 group exhibited greater levels of gastric acid secretion than those of the control and lansoprazole groups. The increase of TNF-α, IL-1β, and COX- 2 expression in 74-week and 2-year-old control rats were inhibited by PMK-S005. In addition, the decrease in HO-1 and NQO-1 protein expression that occurred with aging was inhibited by PMK-S005 in the 74-week-old rats.
CONCLUSIONS These results suggest that PMK-S005 has therapeutic potential as an antiaging agent to ameliorate age-related gastric acid secretion, inflammation, and oxidative stress in the stomach.
PubMed IF 4.1 소화기내과
21252016

제1저자 김재환 · 교신저자 류지곤

, , ,
MicroRNA 141 Expression Is a Potential Prognostic Marker of Biliary Tract Cancers.
Gut Liver. 2016;10(5):836-41.

Abstract
BACKGROUND/AIMS In recent years, a large number of microribonucleic acids (miRNAs) have been identified as putative prognostic biomarkers for solid cancers because of their role in controlling the expression of oncogenes and tumor suppressor genes. The aim of this study was to verify the utility of miRNA 141 as a prognostic biomarker of biliary tract cancers.
METHODS From June 2010 to June 2012, common bile duct cancer tissue samples and matched noncancerous tissues from the ampulla of Vater were obtained from patients with biliary tract cancer undergoing endoscopic retrograde cholangiopancreatography. Using quantitative real-time polymerase chain reaction assays, we measured the mean relative expression levels of miRNA 141 in both groups of tissues. Overexpression of miRNA 141 was defined as a greater than 2-fold increase in expression levels as determined by the 2(-ΔΔCt) method.
RESULTS In a cohort of 38 patients with biliary tract cancers (seven gallbladder, 13 hilar, and 18 distal bile duct cancers), 26 patients (68.4%) were male, and the median age was 69.5 (52 to 85) years. Nineteen patients (50%) had undergone R0 resection procedures, including three Whipple operations, seven pylorus-preserving pancreaticoduodenectomies, six bile duct resections, and three extended lobectomies. Among the patients who had undergone R0 resection, the overexpression of miRNA 141 was significantly associated with shorter disease-free survival and a greater risk of angiolymphatic invasion. Among the patients who did not undergo R0 resection, miRNA 141 overexpression was significantly associated with reduced overall survival.
CONCLUSIONS Overexpression of miRNA 141 is an indicator of a poor prognosis in patients with biliary tract cancer, suggesting that miRNA 141 may be a valuable prognostic biomarker of this disease.
PubMed IF 4.1 소화기내과
21242016

제1저자 서재빈 · 교신저자 김효수

, , , , , , , , , , , , , , ,
Predictors for Side Branch Failure During Provisional Strategy of Coronary Intervention for Bifurcation Lesions (from the Korean Bifurcation Registry).
Am J Cardiol. 2016;118(6):797-803.

Abstract
The most favored strategy for bifurcation lesion is stenting main vessel with provisional side branch (SB) stenting. This study was performed to elucidate predictors for SB failure during this provisional strategy. The study population was patients from 16 centers in Korea who underwent drug-eluting stent implantation for bifurcation lesions with provisional strategy (1,219 patients and 1,236 lesions). On multivariate analysis, the independent predictors for SB jailing after main vessel stenting were SB calcification, large SB reference diameter, severe stenosis of SB, and not taking clopidogrel. Regarding SB compromise, however, the independent predictors were true bifurcation lesion and small SB reference diameter, whereas possible predictors were parent vessel thrombus and parent vessel total occlusion. In addition, SB predilation helps us to get favorable SB outcome. The diameter of SB ostium after main vessel stenting became similar between severe SB lesions treated with predilation and mild SB lesions not treated with predilation. In conclusion, SB calcification, less clopidogrel use, large SB reference diameter, and high SB diameter stenosis are independent predictors for SB jailing, and true bifurcation and small SB reference diameter are independent predictors for SB compromise after main vessel stenting.
PubMed IF 2.5 순환기내과
21232016

제1저자 남아롱, 김지원 · 교신저자 오도연

, , , , , , , , , , , , ,
Therapeutic implication of HER2 in advanced biliary tract cancer.
Oncotarget. 2016;7(36):58007-58021.

Abstract
Currently, there is no validated therapeutic target for biliary tract cancer (BTC). This study aimed to investigate the pre-clinical and clinical implication of HER2 as a therapeutic target in BTC. We established two novel HER2-amplified BTC cell lines, SNU-2670 and SNU-2773, from gallbladder cancer patients. SNU-2670 and SNU-2773 cells were sensitive to trastuzumab, dacomitinib, and afatinib compared with nine HER2-negative BTC cell lines. Dacomitinib and afatinib led to G1 cell cycle arrest in SNU-2773 cells and apoptosis in SNU-2670 cells. Furthermore, dacomitinib, afatinib, and trastuzumab showed synergistic cytotoxicity when combined with some cytotoxic drugs including gemcitabine, cisplatin, paclitaxel, and 5-fluorouracil. In a SNU-2670 mouse xenograft model, trastuzumab demonstrated a good anti-tumor effect as a monotherapy and in combination with gemcitabine increasing apoptosis. In our clinical data, 13.0% of patients with advanced BTC were defined as HER2-positive. Of these, three patients completed HER2-targeted chemotherapy. Two of them demonstrated a partial response, and the other one showed stable disease for 18 weeks. In summary, these pre-clinical and clinical data suggest that HER2 could be a therapeutic target, and that a HER2-targeting strategy should be developed further in patients with HER2-positive advanced BTC.
PubMed IF 5.008 혈액종양내과
21222016

제1저자 임선영, 이정훈 · 교신저자 백승운

, , , , , , , , , , , , , , ,
Subclinical Ascites Does Not Affect the Long-term Prognosis in Hepatitis B Virus-related Cirrhosis Patients Receiving Antivirals.
J Clin Gastroenterol. 2016;50(8):676-85.

Abstract
BACKGROUND AND AIMS This study evaluated the clinical significance of subclinical ascites in patients with hepatitis B virus-related cirrhosis treated with lamivudine (LMV) or entecavir (ETV).
METHODS This multicenter retrospective study involved 8 hospitals. Patients were classified by degree of ascites: (1) no ascites (no ascites on imaging, no diuretics), (2) subclinical ascites (small amount of ascites on imaging, no diuretics), and (3) clinical ascites (moderate to severe ascites or diuretics).
RESULTS Out of 501 patients, 336 (68%), 51 (10%), and 114 (23%) patients were classified as no-ascites, subclinical ascites, and clinical ascites, respectively. In all, 100 (20%) and 401 (80%) were treated with LMV and ETV, respectively. Over 58±24 months of follow-up, 105 patients (21%) developed hepatocellular carcinoma. The cumulative incidence of hepatocellular carcinoma did not differ between LMV-treated and ETV-treated patients (P=0.61); it was higher in the clinical-ascites group than the no-ascites (P=0.054) and subclinical-ascites (P=0.03) groups, but it was comparable between the latter 2 (P=0.225). Forty-five patients (9%) died during follow-up. Survival was significantly shorter in the clinical-ascites group than the other 2 (both P<0.005), but it was comparable between no-ascites and subclinical-ascites groups (P=0.444). Multivariate analysis showed that mortality was significantly associated with prothrombin time [hazard ratio (HR)=2.42; 95% confidence interval (CI), 1.59-3.70], serum albumin (HR=0.54; 95% CI, 0.29-0.99), and presence of clinical ascites (HR=3.58; 95% CI, 1.54-8.30).
CONCLUSIONS Subclinical ascites did not affect prognosis in patients with hepatitis B virus-related cirrhosis receiving antiviral treatment.
PubMed IF 2.7 소화기내과
21212016

제1저자 김정현 · 교신저자 윤성수

, , , , , , ,
SLC29A1 (ENT1) polymorphisms and outcome of complete remission in acute myeloid leukemia.
Cancer Chemother Pharmacol. 2016;78(3):533-40.

Abstract
PURPOSE The solute carrier family 29 (equilibrative nucleoside transporter), member 1 (SLC29A1) is known to be involved in the transportation and resistance of the nucleoside analog cytosine arabinoside (AraC), one of the most effective drugs in the treatment of acute myeloid leukemia (AML).
METHODS In vitro functional analysis in AML cells and genetic association study were performed.
RESULTS Our functional analysis of SLC29A1 on anticancer effects of AraC showed that cytotoxic effects of AraC in AML cell lines were decreased by the reduction of SLC29A1 expression (P < 0.05). To investigate whether SLC29A1 polymorphisms could affect the achievement of complete remission (CR) in AML, we genotyped a total of six common single nucleotide polymorphisms on SLC29A1 in 103 AML patients, including 17 successes and 86 failures in CR. As a result, rs3734703 in 3'-untranslated region was significantly associated with CR even after correction for multiple testing (Fisher's exact test, P = 0.008; P corr = 0.04). A haplotype, ht3 (A-G-G-T-C-A; frequency = 0.294 in success group; frequency = 0.120 in failure group), also revealed a significant association with CR (P = 0.01; simulated P sim = 0.02).
CONCLUSIONS Although further replication in larger subjects and further functional evaluations are required, our results suggest the contribution of SLC29A1 to cytotoxic effects of AraC. In addition, genetic variations of SLC29A1 could be a potential marker for the achievement of CR of cancers of white blood cells including AML.
PubMed IF 2.5 혈액종양내과
21202016

제1저자 서원우 · 교신저자 김학령

, , , , , , , , ,
Incremental prognostic value of high-sensitive C-reactive protein in patients undergoing coronary computed tomography angiography.
J Cardiol. 2016;68(3):222-8.

Abstract
BACKGROUND This study was performed to investigate whether combined use of high-sensitivity C-reactive protein (hs-CRP) levels and coronary computed tomography angiography (CCTA) results have additional prognostic value for predicting cardiovascular events in patients with suspected coronary artery disease (CAD).
METHODS A total of 445 patients (61.6±9.3 years and 62.9% men) with suspected CAD who underwent both CCTA and hs-CRP measurement within one month were evaluated. Information on cardiovascular events, including cardiac death, non-fatal myocardial infarction, unstable angina and late (≥six months after CCTA) coronary revascularization was assessed.
RESULTS One hundred and eighty-five patients (41.6%) had obstructive CAD on CCTA (stenosis ≥50%). Both high hs-CRP (≥2.25mg/L) and obstructive CAD were the independent predictors of cardiovascular events. Kaplan-Meier analysis showed that event rates were significantly different according to the presence of obstructive CAD and hs-CRP levels. Addition of hs-CRP levels to combined information of clinical factors and CCTA results further increased the predictive power for cardiovascular events (global chi-square ratio, from 13.51 to 19.14, p=0.022). Event risks were approximately 21.0-fold higher in the highest-risk group with both obstructive CAD and high hs-CRP levels than in the lowest-risk group with both insignificant CAD and low hs-CRP levels (p=0.007).
CONCLUSIONS Combined use of hs-CRP levels and CCTA results provided a significant improvement in prognostic power for cardiovascular events in patients with suspected CAD. hs-CRP measurement may be a simple and useful method for determining risk stratification and treatment strategy in patients undergoing CCTA.
PubMed IF 3.5 순환기내과
21192016

제1저자 조재영 · 교신저자 이춘택

, , , , , , , ,
Long-Term Follow-up of Small Pulmonary Ground-Glass Nodules Stable for 3 Years: Implications of the Proper Follow-up Period and Risk Factors for Subsequent Growth.
J Thorac Oncol. 2016;11(9):1453-9.

Abstract
INTRODUCTION How long persistent and stable ground-glass nodules (GGNs) should be followed is uncertain, although a minimum of 3 years is suggested. Here, we evaluated a group of GGNs that had remained stable for an initial period of 3 years with the aim of determining the proportion of GGNs showing subsequent growth after the initial 3 years and identifying the clinical and radiologic factors associated with subsequent growth.
METHODS We retrospectively analyzed patients who underwent further computed tomography (CT) after the initial 3-year follow-up period showing a persistent and stable GGN (at least 5 years of follow-up from the initial CT).
RESULTS Between May 2003 and June 2015, 453 GGNs (438 pure GGNs and 15 part-solid GGNs) were found in 218 patients. Of the 218 patients, 14 had 15 GGNs showing subsequent growth after the initial 3 years during the median follow-up period of 6.4 years. For the person-based analysis, the frequency of subsequent growth of GGNs that had been stable during the initial 3 years was 6.7% (14 of 218). For the nodule-based analysis, the frequency was 3.3% (15 of 453). In a multivariate analysis, age 65 years or older (OR = 5.51, p = 0.012), history of lung cancer (OR = 6.44, p = 0.006), initial size 8 mm or larger (OR = 5.74, p = 0.008), presence of a solid component (OR = 16.58, p = 0.009), and air bronchogram (OR = 5.83, p = 0.015) were independent risk factors for subsequent GGN growth.
CONCLUSIONS For the individuals with GGNs having the aforementioned risk factors, the longer follow-up period is required to confirm subsequent GGN growth.
PubMed IF 23.3 호흡기내과
21182016

제1저자 정재우 · 교신저자 강혜련

, , , , ,
Outcomes of corticosteroid prophylaxis for hypersensitivity reactions to low osmolar contrast media in high-risk patients.
Ann Allergy Asthma Immunol. 2016;117(3):304-309.e1.

Abstract
BACKGROUND Corticosteroid prophylaxis has been widely adopted for the prevention of acute allergic-like reactions to iodinated contrast media, but its use is still controversial because there is no strong evidence supporting its efficacy before administration of nonionic low osmolar contrast media (LOCM).
OBJECTIVE To assess the outcomes of premedication in patients with previous acute allergic-like reactions to LOCM in clinical practice.
METHODS A retrospective study was performed on 322 high-risk patients who were reexposed to LOCM after premedication composed of antihistamines and/or systemic corticosteroids because of a previous history of acute allergic-like reactions to LOCM.
RESULTS After premedication, 275 patients (85.4%) did not experience any reaction, but 47 patients (14.6%) still experienced a breakthrough reaction. The premedication rate and amount of corticosteroid administered were significantly higher in the nonrecurrence group than in the recurrence group (P = .04 and P = .04, respectively), and a linear trend was observed in the use of corticosteroid premedication and the efficacy of prevention (P for trend = .02). Multivariate binary logistic regression revealed that corticosteroid premedication was effective in preventing recurrence (odds ratio, 0.284; 95% confidence interval, 0.103-0.784). Nonetheless, despite corticosteroid premedication, 3.4% of high-risk patients still experienced moderate to severe reactions, and 14.3% of patients with a severe index reaction again had a severe reaction.
CONCLUSION Premedication with corticosteroids seems to be helpful in reducing the overall rate of recurrence of acute allergic-like reactions to LOCM in high-risk patients, but patients with severe index reactions are still at risk of developing severe reactions despite corticosteroid premedication.
PubMed IF 7.1 알레르기내과
21172016

제1저자 강지훈 · 교신저자 박경우

, , , , , ,
Usefulness of the Baseline Syntax Score to Predict 3-Year Outcome After Complete Revascularization by Percutaneous Coronary Intervention.
Am J Cardiol. 2016;118(5):641-6.

Abstract
Although we strive to achieve complete revascularization (CR) in those receiving percutaneous coronary intervention, it is uncertain which of these patients are at increased risk of clinical events. In this study, we aimed to investigate whether the baseline SYNTAX score (bSS) can predict adverse clinical events in patients receiving CR. From the Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss After Stenting registry, the 3-year patient-oriented composite end point (POCE; all cause death, any myocardial infarction, and any revascularization) was compared according to bSS tertiles (1 ≤ low bSS < 6, 6 ≤ mid-bSS < 10, high bSS ≥ 10). Of the 5,088 patients, CR was achieved in 2,173 by percutaneous coronary intervention. The 3-year POCE increased significantly along with bSS tertile (7.3% vs 8.4% vs 14.8%, p <0.001). Multivariate analysis showed that, despite having the same residual SS of 0, the bSS was an independent predictor of 3-year POCE (hazard ratio 1.038, 95% confidence interval 1.018 to 1.058, p <0.001 per bSS point). In subgroup analysis, bSS was a predictor for 3-year POCE in multivessel diseases (hazard ratio 1.029, 95% confidence interval 1.004 to 1.054, p = 0.025 per bSS point), whereas in single-vessel diseases, the discriminative value of bSS was less significant. Also the clinical SYNTAX score, which added age, creatinine level, and ejection fraction to the bSS, was superior to the bSS in predicting 3-year POCE (area under the curve 0.595 vs 0.649, p = 0.008). In conclusion, the bSS was an independent predictor of long-term clinical outcomes in patients receiving CR, especially in those with multivessel coronary artery disease. Adding clinical factors to the bSS could increase the predictive power of clinical outcomes.
PubMed IF 2.5 순환기내과
21162016

제1저자 강지훈, 박종한 · 교신저자 박진주

, , , ,
The effects of erythropoiesis stimulating therapy for anemia in chronic heart failure: A meta-analysis of randomized clinical trials.
Int J Cardiol. 2016;218:12-22.

Abstract
BACKGROUND Although anemia is common in chronic heart failure (CHF), the use of erythropoiesis stimulating agents (ESAs) in CHF patients remains controversial. In this meta-analysis, we sought to clarify the efficacy and safety of ESAs in anemic patients with CHF.
METHODS We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, the U.S. National Institutes of Health registry of clinical trials. We included 13 randomized clinical trials (RCTs) in the meta-analysis. The co-primary outcome was all-cause mortality and rehospitalization. The safety analysis outcome was thromboembolic events.
RESULTS Preliminary analysis showed that ESA-treatment did not have any effect for all-cause mortality and rehospitalization. However, we revealed a significant small-study bias, and used the trim-and-fill method to reduce this bias. The summary effect of ESA-treatment was insignificant for all-cause mortality (risk ratio [RR] 0.91, 95% confidence interval [CI] 0.59-1.42, p=0.69) and for rehospitalization (RR 0.91, 95% CI 0.67-1.23, p=0.53). Regarding symptoms, ESA-treatment improved dyspnea (NYHA grade improvement: 1.63, 95% CI 0.65-2.62, p<0.001) and quality-of-life measured by subjective questionnaires. However, in safety analysis, ESAs increased the over-all risk for thromboembolic events (RR 1.28, 95% CI 1.03-1.58, p=0.026), however, no specific increase was observed in severe thromboembolic events. Subgroup analysis showed no difference in ESA-treatment according to the type of ESAs (darbepoetin vs. erythropoietin) and between studies of different follow-up durations (<6months or ≥6months).
CONCLUSION Among CHF patients with anemia, ESA-treatment has a neutral effect on all-cause mortality and rehospitalization and improves symptoms, but has harmful effects on thromboembolic events.
PubMed IF 3.3 순환기내과
21152016

제1저자 이도영 · 교신저자 박영주, 하정훈

, , , , , , , ,
Recurrence and Survival After Gross Total Removal of Resectable Undifferentiated or Poorly Differentiated Thyroid Carcinoma.
Thyroid. 2016;26(9):1259-68.

Abstract
BACKGROUND This study aimed to evaluate the recurrence and survival after initial curative-intent surgery of resectable anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC).
METHODS A retrospective analysis was conducted on patients with ATC and PDTC who had been treated between 1985 and 2013. Among them, 119 patients who had undergone surgery with curative intent were included in this study. The outcome measures included the clinical response to treatment and the recurrence rates of three separate thyroid cancer groups: ATC, differentiated thyroid cancer (DTC) with anaplastic foci, and PDTC.
RESULTS Initial remission was achieved in 100 (84.0%) patients, with higher percentages in patients with DTC with anaplastic foci (97.8%) and PDTC (96.7%) compared with ATC (60.5%). The overall recurrence rate after initial remission was 30.8% in ATC, 25.9% in PDTC, and 6.7% in DTC with anaplastic foci. Pathologic diagnosis, preexisting goiter or tumors, along with tracheal and lymphatic/vascular invasion were correlated with recurrence (p < 0.001; p = 0.001, 0.006, 0.003, and 0.016, respectively). All patients without initial remission died due to local failure, and most patients with recurrence, apart from two PDTC patients, had distant metastasis. Overall mortality after initial curative-intent surgery was 58.1% in ATC, 8.7% in DTC with anaplastic foci, and 20% in PDTC.
CONCLUSIONS The initial remission of resectable tumors was higher and the recurrence rate was lower in DTC with anaplastic foci and PDTC compared with ATC. Careful monitoring of the development of distant metastasis is necessary, especially in patients with aggressive pathology with tracheal and lymphovascular invasion.
PubMed IF 6.6 내분비대사내과
21142016

제1저자 박준빈 · 교신저자 김형관

, , , , , , , , , , , , , ,
Prognostic Value of Cardiac MR Imaging for Preoperative Assessment of Patients with Severe Functional Tricuspid Regurgitation.
Radiology. 2016;280(3):723-34.

Abstract
Purpose To explore the prognostic value of cardiac magnetic resonance (MR) imaging in predicting postoperative cardiac death in patients with severe functional tricuspid regurgitation (TR). Materials and Methods This study was approved by the institutional review board, and written informed consent was obtained from all patients. Prospectively collected data included cardiac MR images, New York Heart Association (NYHA) functional class, a comprehensive laboratory test, and clinical events over the follow-up period in 75 consecutive patients (61 women and 14 men; mean age ± standard deviation, 59 years ± 9) undergoing corrective surgery for severe functional TR. Cox proportional hazards models were used to assess the association between cardiac MR parameters and outcomes. Results During a median follow-up period of 57 months (range, 21-82 months), cardiac mortality and all-cause mortality were 17.3% and 26.7%, respectively, with a surgical mortality of 6.7%. Cardiac death risk was lower with a higher right ventricular (RV) ejection fraction (EF) on cardiac MR images (hazard ratio per 5% higher EF = 0.790, P = .048). By adjusting for confounding variables, RV EF remained a significant predictor for cardiac death (P < .05) and major postoperative cardiac events (P < .05). The area under the receiver operating characteristic curve (AUC) confirmed the incremental role of RV EF on cardiac MR images in the prediction of postoperative cardiac death (AUC, 0.681-0.771; P = .041) and major postoperative cardiac events (AUC, 0.660-0.745; P = .044) on top of NYHA class. RV end-systolic volume index was also independently associated with these outcomes but failed to increase the AUC significantly. Conclusion Preoperative assessment of cardiac MR imaging-based RV EF provides independent and incremental prognostic information in patients undergoing corrective surgery for severe functional TR. (©) RSNA, 2016 Online supplemental material is available for this article.
PubMed IF 17.6 순환기내과
21132016

제1저자 김정현 · 교신저자 이진우

, , , , , , , , ,
Factors influencing the initiation of intensive care in elderly patients and their families: A retrospective cohort study.
Palliat Med. 2016;30(8):789-99.

Abstract
BACKGROUND The number of elderly patients admitted to the intensive care unit is constantly growing. However, a decision regarding intensive care in these populations remains a challenge.
AIM To identify factors that influences the decision of elderly patients and their families about whether to initiate intensive care in case of an acute event.
DESIGN/PARTICIPANTS Medical records of patients (>80 years), who were admitted to general wards and referred for intensive care, were retrospectively reviewed. Patients who received intensive care were compared with those not agreeing to the initiation of intensive care.
RESULTS Among the 125 patients, 45 agreed to receiving intensive care. Baseline characteristics at the time of intensive care unit referral were similar between the intensive care and non-intensive care groups. Only one patient had advance directives before the intensive care unit referral. Lower economic status (odds ratio = 0.27, 95% confidence interval = 0.08-0.94) and cognitive impairment (odds ratio = 0.20, 95% confidence interval = 0.07-0.56) were found associated with a lower likelihood of agreeing to intensive care, while a large number of participants involved in the decision-making process were associated with a higher likelihood of intensive care unit use (odds ratio = 1.82, 95% confidence interval = 1.08-3.09). Mean duration of hospital stay was longer for the intensive care group as compared with the non-intensive care group (28.8 days and 19.8 days, respectively, p = 0.03). However, there was no significant difference in the survival rate.
CONCLUSION The initiation of intensive care in elderly patients was influenced not only by medical conditions but also by the patient's economic status and the number of family members involved in the decision-making process.
PubMed IF 6.4 호흡기내과
21122016

제1저자 최선미, 장안희 · 교신저자 김영환

, , , ,
Metformin Reduces Bleomycin-induced Pulmonary Fibrosis in Mice.
J Korean Med Sci. 2016;31(9):1419-25.

Abstract
Metformin has anti-inflammatory and anti-fibrotic effects. We investigated whether metformin has an inhibitory effect on bleomycin (BLM)-induced pulmonary fibrosis in a murine model. A total of 62 mice were divided into 5 groups: control, metformin (100 mg/kg), BLM, and BLM with metformin (50 mg/kg or 100 mg/kg). Metformin was administered to the mice orally once a day from day 1. We sacrificed half of the mice on day 10 and collected the bronchoalveolar lavage fluid (BALF) from their left lungs. The remaining mice were sacrificed and analyzed on day 21. The right lungs were harvested for histological analyses. The messenger RNA (mRNA) levels of epithelial-mesenchymal transition markers were determined via analysis of the harvested lungs on day 21. The mice treated with BLM and metformin (50 mg/kg or 100 mg/kg) showed significantly lower levels of inflammatory cells in the BALF compared with the BLM-only mice on days 10 and 21. The histological examination revealed that the metformin treatment led to a greater reduction in inflammation than the treatment with BLM alone. The mRNA levels of collagen, collagen-1, procollagen, fibronectin, and transforming growth factor-β in the metformin-treated mice were lower than those in the BLM-only mice on day 21, although statistical significance was observed only in the case of procollagen due to the small number of live mice in the BLM-only group. Additionally, treatment with metformin reduced fibrosis to a greater extent than treatment with BLM alone. Metformin suppresses the inflammatory and fibrotic processes of BLM-induced pulmonary fibrosis in a murine model.
PubMed IF 3.2 호흡기내과
21112016

제1저자 이하정, 이재욱 · 교신저자 양승희

, , , , , , , ,
Cln 3-requiring 9 is a negative regulator of Th17 pathway-driven inflammation in anti-glomerular basement membrane glomerulonephritis.
Am J Physiol Renal Physiol. 2016;311(3):F505-19.

Abstract
T helper 17 (Th17) lymphocytes promote renal inflammation in anti-glomerular basement membrane glomerulonephritis (anti-GBM GN), and signal transducer and activator of transcription 3 (STAT3) mediates activation of Th17 lymphocytes by IL-6 and transforming growth factor-β (TGF-β). Cln 3-requiring 9 (Ctr9), a subunit of RNA polymerase-associated factor complex (PAFc), regulates the transcription of IL-6/STAT3-dependent genes. Here, we investigated the role of Ctr9 in regulating Th17-driven inflammation in anti-GBM GN. In mice, STAT3β or IL-17 knockout ameliorated anti-GBM autoantibody-induced renal injury. This phenomenon was associated with decreases in retinoic acid receptor-related orphan receptor γt (RORγt), IL-17, phosphorylated STAT3, and proinflammatory cytokines. Compared with wild-type mice, Ctr9 increased in both STAT3β(-/-) and IL-17(-/-) mice injected with anti-GBM IgG, showing a negative correlation with Th17-related transcripts. Small interfering RNA (siRNA)-mediated knockdown of Ctr9 in intrarenal lymphocytes further upregulated Th17-related transcripts, consistent with repression of Th17 differentiation by Ctr9. Interestingly, Ctr9 was also expressed in human and mouse mesangial cells and downregulated in response to anti-GBM IgG or to TGF-β plus IL-17. Ctr9 in mesangial cells was even more repressed in the presence of both anti-GBM IgG and Th17-activating cytokines. Consistent with these findings, renal biopsies obtained from patients with anti-GBM GN showed consistent downregulation of Ctr9 and upregulation of phosphorylated STAT3 and IL-17 in the glomerulus. We conclude that Ctr9 is a negative regulator of Th17 differentiation in anti-GBM GN and repressed by anti-GBM IgG and IL-17 in mesangial cells.
PubMed IF 3.6 신장내과
21102016

제1저자 장미경 · 교신저자 김상완

, , , , , , , ,
Intermittent PTH treatment can delay the transformation of mature osteoblasts into lining cells on the periosteal surfaces.
J Bone Miner Metab. 2016;34(5):532-9.

Abstract
Mature osteoblasts have three fates: as osteocytes, quiescent lining cells, or osteoblasts that undergo apoptosis. However, whether intermittent parathyroid hormone (PTH) can modulate the fate of mature osteoblasts in vivo is uncertain. We performed a lineage-tracing study using an inducible gene system. Dmp1-CreERt2 mice were crossed with Rosa26R reporter mice to obtain targeted mature osteoblasts and their descendants, lining cells or osteocytes, which were detected using X-gal staining. Rosa26R:Dmp1-CreERt2(+) mice were injected with 0.25 mg 4-OH-tamoxifen (4-OHTam) on postnatal days 5, 7, 9, 16, and 23. In a previous study, at 22 days after the last 4-OHTam, most LacZ+ cells on the periosteal surface were inactive lining cells. On day 25 (D25), the mice were challenged with an injection of human PTH (1-34, 80 μg/kg) or vehicle daily for 10 (D36) or 20 days (D46). We evaluated the number and thickness of LacZ+ osteoblast descendants in the calvaria and tibia. In the vehicle group, the number and thickness of LacZ+ osteoblast descendants at both D36 and D46 significantly decreased compared to D25, which was attenuated in the PTH group. In line with these results, PTH inhibited the decrease in the number of LacZ+/osteocalcin-positive cells compared to vehicle at both D36 and D46. As well, the serum levels of sclerostin decreased, as did the protein expression of sclerostin in the cortical bone. These results suggest that intermittent PTH treatment can increase the number of periosteal osteoblasts by preventing mature osteoblasts from transforming into lining cells in vivo.
PubMed IF 2.9 내분비대사내과
21092016

제1저자 조유리 · 교신저자 윤정환

, , , , , ,
Hypoxia Enhances Tumor-Stroma Crosstalk that Drives the Progression of Hepatocellular Carcinoma.
Dig Dis Sci. 2016;61(9):2568-77.

Abstract
BACKGROUND Crosstalk between tumor cells and their microenvironment plays a crucial role in the progression of hepatocellular carcinoma (HCC). Hypoxia, a common feature of advanced HCC, has been shown to modulate the evolution of the tumor microenvironment. In this study, we investigated the effect of hypoxia on tumor-stroma crosstalk in HCC.
METHODS Human HCC cell lines (Huh-BAT, SNU-475) were cocultured with an activated human hepatic stellate cell line (HSCs; LX-2) under either normoxic or hypoxic conditions. Cell growth was evaluated with the MTS assay. Apoptotic signaling cascades were assessed by immunoblot analysis. Expression of CD31 and phosphorylated (p-) Akt in HCC tissues was detected by immunohistochemistry.
RESULTS Coculturing HCC cells with HSCs under hypoxic conditions enhanced their proliferation, migration, and resistance to bile acid (BA)-induced apoptosis compared to coculturing under normoxic conditions. Under hypoxia, of various HSC-derived growth factors, PDGF-BB was the most up-regulated, leading to the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in HCC cells. Immunohistochemical study also revealed that p-Akt was highly expressed in hypoxic, hypovascular HCC as compared to hypervascular HCC. Neutralizing antisera to PDGF-BB or a PI3K inhibitor attenuated the proliferation of HCC cells cocultured with HSCs, and sensitized HCC cells to BA-induced apoptosis, especially under hypoxic conditions.
CONCLUSIONS In conclusion, hypoxic HSC-derived PDGF-BB stimulates the proliferation of HCC cells through activation of the PI3K/Akt pathway, while the inhibition of PDGF-BB or PI3K/Akt pathways enhances apoptotic cell death. Targeting tumor-stroma crosstalk might be a novel therapy in the management of human HCCs.
PubMed IF 2.8 소화기내과
21082016

제1저자 이주명 · 교신저자 구본권, 천기정

, , , , , , , , , , , , , , ,
Integrated Myocardial Perfusion Imaging Diagnostics Improve Detection of Functionally Significant Coronary Artery Stenosis by 13N-ammonia Positron Emission Tomography.
Circ Cardiovasc Imaging. 2016;9(9):CIRCIMAGING.116.004768.

Abstract
BACKGROUND Recent evidence suggests that the diagnostic accuracy of myocardial perfusion imaging is improved by quantifying stress myocardial blood flow (MBF) in absolute terms. We evaluated a comprehensive quantitative (13)N-ammonia positron emission tomography ((13)NH3-PET) diagnostic panel, including stress MBF, coronary flow reserve (CFR), and relative flow reserve (RFR) in conjunction with relative perfusion defect (PD) assessments to better detect functionally significant coronary artery stenosis.
METHODS AND RESULTS A total of 130 patients (307 vessels) with coronary artery disease underwent both (13)NH3-PET and invasive coronary angiography with fractional flow reserve (FFR) measurement. Diagnostic accuracy, optimal cut points, and discrimination indices of respective (13)NH3-PET quantitative measures were compared, with FFR as standard reference. The capacity to discern disease with stepwise addition of stress MBF, CFR, and RFR to qualitatively assessed relative PD was also gauged, using the category-free net reclassification index. All quantitative measures showed significant correlation with FFR (PET-derived CFR, r=0.388; stress MBF, r=0.496; and RFR, r=0.780; all P<0.001). Optimal respective cut points for FFR ≤0.8 and ≤0.75 were 1.99 and 1.84 mL/min per g for stress MBF and 2.12 and 2.00 for PET-derived CFR. Discrimination indices of quantitative measures that correlated with FFR ≤0.8 were all significantly higher than that of relative PD (area under the curve: 0.626, 0.730, 0.806, and 0.897 for relative PD, CFR, stress MBF, and RFR, respectively; overall comparison P<0.001). The capacity for functionally significant coronary stenosis was incrementally improved by the successive addition of CFR (net reclassification index=0.629), stress MBF (net reclassification index=0.950), and RFR (net reclassification index=1.253; all P<0.001) to relative PD.
CONCLUSIONS Integrating quantitative (13)NH3-PET measures with qualitative myocardial perfusion assessment provides superior diagnostic accuracy and improves the capacity to detect functionally significant coronary artery stenosis.
CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01621438 and NCT01366404.
PubMed IF 9.1 순환기내과
21072016

제1저자 서기현, 김민재 · 교신저자 송경호

, , , , , , , , , , ,
Cancer-specific incidence rates of tuberculosis: A 5-year nationwide population-based study in a country with an intermediate tuberculosis burden.
Medicine (Baltimore). 2016;95(38):e4919.

Abstract
Population-based studies of the incidence of tuberculosis in cancer patients according to the type of cancer are limited. We investigated the cancer-specific incidence of tuberculosis in a nationwide population-based cohort in a country with an intermediate burden of tuberculosis.We used mandatory National Health Insurance claims data to construct a cancer cohort of adults (aged 20-99 years) with newly diagnosed malignancies other than lung cancer, from January 2008 to December 2012. Patients who developed tuberculosis in this period were identified in the cancer cohort and the general population. Standardized incidence ratios (SIRs) of tuberculosis in the cancer cohort according to type of cancer and time after cancer diagnosis were calculated by comparing the observed incidence rates with those inferred from the age- and gender-specific incidence rates in the general population.A total of 855,382 cancer patients and 1589,876 person-years (py) were observed. A total of 5745 patients developed tuberculosis; the mean incidence rate was 361.3 per 100,000 py, and the SIR was 2.22 (95% confidence interval [CI], 2.17-2.27). The incidence rate was highest for hematologic malignancy and lowest for thyroid cancer. It was also highest as 650.1 per 100,000 py, with SIR of 3.70 (CI, 3.57-3.83) for the first 6 months after diagnosis of malignancy and then declined. However, it still remained higher than that of the general population after 24 months (SIR = 1.43, CI, 1.36-1.51).The incidence of tuberculosis increases after diagnosis in patients with malignancies. The risk of tuberculosis differs according to the type of cancer and remains elevated even 24 months after cancer diagnosis. Tuberculosis should be considered an important comorbidity in patients with malignancies.
PubMed IF 2 감염내과
21062016

제1저자 김윤기 · 교신저자 서정원

, , , , , , , , ,
Cigarette Smoking Does Not Enhance Clopidogrel Responsiveness After Adjusting VerifyNow P2Y12 Reaction Unit for the Influence of Hemoglobin Level.
JACC Cardiovasc Interv. 2016;9(16):1680-90.

Abstract
OBJECTIVES The authors performed this analysis to examine whether the enhanced clopidogrel responsiveness in current smokers is maintained after adjusting the influence of hemoglobin on VerifyNow P2Y12 reaction unit (PRU).
BACKGROUND PRU is consistently reported to be lower in current smokers. However, PRU has a significant inverse relationship with hemoglobin level, and smokers have higher hemoglobin levels. Because the association between PRU and hemoglobin is likely to be an in vitro phenomenon, we hypothesized that the observed difference in PRU between nonsmokers and current smokers is the result of confounding effect of hemoglobin rather than true difference in platelet reactivity.
METHODS Three cohorts were combined for the analysis (SNUBH [Seoul National University Bundang Hospital], n = 459; CILON-T [influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation], n = 715; HOST-ASSURE [Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen], n = 1,357). The final combined cohort consisted of 1,314 patients who underwent percutaneous coronary intervention and had VerifyNow P2Y12 assay results. General linear model (analysis of covariance) was used to control the effect of hemoglobin on PRU.
RESULTS A significant inverse correlation was observed between PRU and hemoglobin (r = -0.389; p < 0.001). Current smokers showed a significantly higher hemoglobin level (13.5 ± 1.6 vs. 14.4 ± 1.5; p < 0.001) but lower PRU level (230.1 ± 90.7 vs. 212.2 ± 83.6; p < 0.001). After adjusting the influence of hemoglobin on PRU, there was no difference in PRU between nonsmokers and current smokers (224.1 [95% confidence interval: 218.7 to 229.5] vs. 225.3 [95% confidence interval: 217.2 to 233.3]; p = 0.813).
CONCLUSIONS The observed difference in PRU between nonsmokers and current smokers is largely attributable to the difference in hemoglobin level. Enhanced clopidogrel responsiveness in cigarette smokers is not confirmed in this study and the concept of the smokers' paradox needs further validation.
PubMed IF 12.7 순환기내과
21052016

제1저자 김문석 · 교신저자 송경호

, , , , , , , , , , , ,
Electronic Alerts with Automated Consultations Promote Appropriate Antimicrobial Prescriptions.
PLoS One. 2016;11(8):e0160551.

Abstract
BACKGROUND To promote appropriate antimicrobial use in bloodstream infections (BSIs), we initiated an intervention program consisting of electronic alerts and automated infectious diseases consultations in which the identification and antimicrobial susceptibility test (ID/AST) results were reported.
METHODS We compared the appropriateness of antimicrobial prescriptions and clinical outcomes in BSIs before and after initiation of the program. Appropriateness was assessed in terms of effective therapy, optimal therapy, de-escalation therapy, and intravenous to oral switch therapy.
RESULTS There were 648 BSI episodes in the pre-program period and 678 in the program period. The proportion of effective, optimal, and de-escalation therapies assessed 24 hours after the reporting of the ID/AST results increased from 87.8% (95% confidence interval [CI] 85.5-90.5), 64.4% (95% CI 60.8-68.1), and 10.0% (95% CI 7.5-12.6) in the pre-program period, respectively, to 94.4% (95% CI 92.7-96.1), 81.4% (95% CI 78.4-84.3), and 18.6% (95% CI 15.3-21.9) in the program period, respectively. Kaplan-Meier analyses and log-rank tests revealed that the time to effective (p<0.001), optimal (p<0.001), and de-escalation (p = 0.017) therapies were significantly different in the two periods. Segmented linear regression analysis showed the increase in the proportion of effective (p = 0.015), optimal (p<0.001), and de-escalation (p = 0.010) therapies at 24 hours after reporting, immediately after program initiation. No significant baseline trends or changes in trends were identified. There were no significant differences in time to intravenous to oral switch therapy, length of stay, and 30-day mortality rate.
CONCLUSION This novel form of stewardship program based on intervention by infectious disease specialists and information technology improved antimicrobial prescriptions in BSIs.
PubMed IF 2.8 감염내과
21042016

제1저자 박진선, 신준한 · 교신저자 김효수

, , , , , , , , , , , , , , , ,
Efficacy and safety of fixed-dose combination therapy with olmesartan medoxomil and rosuvastatin in Korean patients with mild to moderate hypertension and dyslipidemia: an 8-week, multicenter, randomized, double-blind, factorial-design study (OLSTA-D RCT: OLmesartan rosuvaSTAtin from Daewoong).
Drug Des Devel Ther. 2016;10:2599-609.

Abstract
The pill burden of patients with hypertension and dyslipidemia can result in poor medication compliance. This study aimed to evaluate the efficacy and safety of fixed-dose combination (FDC) therapy with olmesartan medoxomil (40 mg) and rosuvastatin (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. This multicenter, randomized, double-blind, factorial-design study included patients aged ≥20 years with mild to moderate essential hypertension and dyslipidemia. Patients were randomly assigned to receive FDC therapy (40 mg olmesartan medoxomil, 20 mg rosuvastatin), 40 mg olmesartan medoxomil, 20 mg rosuvastatin, or a placebo. The percentage change from baseline in low-density lipoprotein cholesterol levels was compared between FDC therapy and olmesartan medoxomil, and the change from baseline in diastolic blood pressure was compared between FDC therapy and rosuvastatin 8 weeks after treatment. A total of 162 patients were included. The least square mean percentage change (standard error) from baseline in low-density lipoprotein cholesterol levels 8 weeks after treatment was significantly greater in the FDC than in the olmesartan medoxomil group (-52.3% [2.8%] vs -0.6% [3.5%], P<0.0001), and the difference was -51.7% (4.1%) (95% confidence interval: -59.8% to -43.6%). The least square mean change (standard error) from baseline in diastolic blood pressure 8 weeks after treatment was significantly greater in the FDC group than in the rosuvastatin group (-10.4 [1.2] mmHg vs 0.1 [1.6] mmHg, P<0.0001), and the difference was -10.5 (1.8) mmHg (95% confidence interval: -14.1 to -6.9 mmHg). There were 50 adverse events in 41 patients (22.7%) and eight adverse drug reactions in five patients (2.8%). The study found that FDC therapy with olmesartan medoxomil and rosuvastatin is an effective, safe treatment for patients with hypertension and dyslipidemia. This combination may improve medication compliance in patients with a large pill burden.
PubMed IF 6.1 순환기내과
21032016

제1저자 박재윤 · 교신저자 이정표

, , , , , , , , , , , ,
Early initiation of continuous renal replacement therapy improves survival of elderly patients with acute kidney injury: a multicenter prospective cohort study.
Crit Care. 2016;20(1):260.

Abstract
BACKGROUND Continuous renal replacement therapy (CRRT) is essential in the management of critically ill patients with acute kidney injury (AKI). However, the optimal timing for initiating CRRT remains controversial, especially in elderly patients. Therefore, we investigated the outcomes of early CRRT initiation in elderly patients with AKI.
METHODS A total of 607 patients ≥65 years of age who started CRRT due to AKI between August 2009 and December 2013 were prospectively enrolled. They were divided into two groups based on the median 6-hour urine output immediately before CRRT initiation. Propensity score matching was used to compare the overall survival rate, CRRT duration, and hospitalization duration.
RESULTS The median age of both groups was 73.0 years, and 60 % of the patients were male. The most common cause of AKI was sepsis. In the early CRRT group, the mean arterial pressure was higher, but the prothrombin time and total bilirubin, aspartate aminotransferase, and alanine aminotransferase levels were lower. The overall cumulative survival rate was higher in the early CRRT group (log-rank P < 0.01). Late CRRT initiation was associated with a higher mortality rate than early initiation after adjusting for age, sex, the Charlson comorbidity index, systolic arterial pressure, prothrombin time, the total bilirubin, aspartate aminotransferase, and alanine aminotransferase levels, cumulative fluid balance and diuretic use (hazard ratio, 1.35; 95 % confidence interval 1.06, 1.71, P = 0.02). Following propensity score matching, patient survival was significantly better in the early CRRT group than in the late CRRT group (P < 0.01). The total duration of hospitalization from the start of CRRT was shorter among the survivors when CRRT was started earlier (26.7 versus 39.1 days, P = 0.04).
CONCLUSION A better prognosis can be expected if CRRT is applied early in the course of AKI in critically ill, elderly patients.
PubMed IF 11.4 신장내과
21022016

제1저자 안정남, 안성복 · 교신저자 김영훈, 임춘수

, , , , , , , , , ,
Pre-Transplant Cardiovascular Risk Factors Affect Kidney Allograft Survival: A Multi-Center Study in Korea.
PLoS One. 2016;11(8):e0160607.

Abstract
BACKGROUND Pre-transplant cardiovascular (CV) risk factors affect the development of CV events even after successful kidney transplantation (KT). However, the impact of pre-transplant CV risk factors on allograft failure (GF) has not been reported.
METHODS AND FINDINGS We analyzed the graft outcomes of 2,902 KT recipients who were enrolled in a multi-center cohort from 1997 to 2012. We calculated the pre-transplant CV risk scores based on the Framingham risk model using age, gender, total cholesterol level, smoking status, and history of hypertension. Vascular disease (a composite of ischemic heart disease, peripheral vascular disease, and cerebrovascular disease) was noted in 6.5% of the patients. During the median follow-up of 6.4 years, 286 (9.9%) patients had developed GF. In the multivariable-adjusted Cox proportional hazard model, pre-transplant vascular disease was associated with an increased risk of GF (HR 2.51; 95% CI 1.66-3.80). The HR for GF (comparing the highest with the lowest tertile regarding the pre-transplant CV risk scores) was 1.65 (95% CI 1.22-2.23). In the competing risk model, both pre-transplant vascular disease and CV risk score were independent risk factors for GF. Moreover, the addition of the CV risk score, the pre-transplant vascular disease, or both had a better predictability for GF compared to the traditional GF risk factors.
CONCLUSIONS In conclusion, both vascular disease and pre-transplant CV risk score were independently associated with GF in this multi-center study. Pre-transplant CV risk assessments could be useful in predicting GF in KT recipients.
PubMed IF 2.8 신장내과
21012016

제1저자 조유리, 이윤빈 · 교신저자 이정훈, 윤정환

, , , , , , , , , , ,
Modified AS1411 Aptamer Suppresses Hepatocellular Carcinoma by Up-Regulating Galectin-14.
PLoS One. 2016;11(8):e0160822.

Abstract
Aptamers are small synthetic oligonucleotides that bind to target proteins with high specificity and affinity. AS1411 is an aptamer that binds to nucleolin, which is overexpressed in the cytoplasm and occurs on the surface of cancer cells. We investigated the therapeutic potential of aptamers in hepatocellular carcinoma (HCC) by evaluating anti-tumor effects and confirming the affinity and specificity of AS1411- and modified AS1411-aptamers in HCC cells. Cell growth was assessed using the MTS assay, and cell death signaling was explored by immunoblot analysis. Fluorescence-activated cell sorting was performed to evaluate the affinity and specificity of AS1411-aptamers in SNU-761 HCC cells. We investigated the in vivo effects of the AS1411-aptamer using BALB/c nude mice in a subcutaneous xenograft model with SNU-761 cells. Treatment with a modified AS1411-aptamer significantly decreased in vitro (under normoxic [P = 0.035] and hypoxic [P = 0.018] conditions) and in vivo (under normoxic conditions, P = 0.041) HCC cell proliferation compared to control aptamers. AS1411- and control aptamers failed to control HCC cell proliferation. However, AS1411- and the modified AS1411-aptamer did not induce caspase activation. Decrease in cell growth by AS1411 or modified AS1411 was not prevented by caspase or necrosis inhibitors. In a microarray, AS1411 significantly enhanced galectin-14 expression. Suppression of HCC cell proliferation by the modified AS1411-aptamer was attenuated by galectin-14 siRNA transfection. Modified AS1411-aptamer suppressed HCC cell growth in vitro and in vivo by up-regulating galectin-14 expressions. Modified AS1411-aptamers may have therapeutic potential as a novel targeted therapy for HCC.
PubMed IF 2.8 소화기내과
21002016

제1저자 유승근, 이승복, 김수진 · 교신저자 박영주, 이규언, 서정선

, , , , , , , , , , , , , ,
Comprehensive Analysis of the Transcriptional and Mutational Landscape of Follicular and Papillary Thyroid Cancers.
PLoS Genet. 2016;12(8):e1006239.

Abstract
Follicular thyroid carcinoma (FTC) and benign follicular adenoma (FA) are indistinguishable by preoperative diagnosis due to their similar histological features. Here we report the first RNA sequencing study of these tumors, with data for 30 minimally invasive FTCs (miFTCs) and 25 FAs. We also compared 77 classical papillary thyroid carcinomas (cPTCs) and 48 follicular variant of PTCs (FVPTCs) to observe the differences in their molecular properties. Mutations in H/K/NRAS, DICER1, EIF1AX, IDH1, PTEN, SOS1, and SPOP were identified in miFTC or FA. We identified a low frequency of fusion genes in miFTC (only one, PAX8-PPARG), but a high frequency of that in PTC (17.60%). The frequencies of BRAFV600E and H/K/NRAS mutations were substantially different in miFTC and cPTC, and those of FVPTC were intermediate between miFTC and cPTC. Gene expression analysis demonstrated three molecular subtypes regardless of their histological features, including Non-BRAF-Non-RAS (NBNR), as well as BRAF-like and RAS-like. The novel molecular subtype, NBNR, was associated with DICER1, EIF1AX, IDH1, PTEN, SOS1, SPOP, and PAX8-PPARG. The transcriptome of miFTC or encapsulated FVPTC was indistinguishable from that of FA, providing a molecular explanation for the similarly indolent behavior of these tumors. We identified upregulation of genes that are related to mitochondrial biogenesis including ESRRA and PPARGC1A in oncocytic follicular thyroid neoplasm. Arm-level copy number variations were correlated to histological and molecular characteristics. These results expanded the current molecular understanding of thyroid cancer and may lead to new diagnostic and therapeutic approaches to the disease.
PubMed IF 3.9 내분비대사내과
20992016

제1저자 이희선 · 교신저자 윤연이

, , , , , , , , , , ,
The Incremental Prognostic Value of Cardiac Computed Tomography in Comparison with Single-Photon Emission Computed Tomography in Patients with Suspected Coronary Artery Disease.
PLoS One. 2016;11(8):e0160188.

Abstract
BACKGROUND Coronary computed tomographic angiography (CCTA) facilitates comprehensive evaluation of coronary artery disease (CAD), including plaque characterization, and can provide additive diagnostic value to single-photon emission computed tomography (SPECT). However, data regarding the incremental prognostic value of CCTA to SPECT remain sparse. We evaluated the independent and incremental prognostic value of CCTA, as compared with clinical risk factors and SPECT.
MATERIALS AND METHODS A total of 1,077 patients with suspected CAD who underwent both SPECT and cardiac CT between 2004 and 2012 were enrolled retrospectively. Presence of reversible or fixed perfusion defect (PD) and summed stress score were evaluated on SPECT. Presence, extent of coronary atherosclerosis and diameter stenosis (DS) were evaluated on CCTA. Plaque composition was categorized as non-calcified, mixed, or calcified according to the volume of calcified component (>130 Hounsfield Units). Patients were followed up for the occurrence of adverse cardiac events including cardiac death, non-fatal myocardial infarction, unstable angina, and late revascularization (>90 days after imaging studies).
RESULTS During follow-up (median 23 months), adverse cardiac events were observed in 71 patients (6.6%). When adjusted for clinical risk factors and SPECT findings, the presence of any coronary plaque, any plaque in ≥3 segments, coronary artery calcium score (CACS) ≥400, a plaque ≥50% DS, presence of non-calcified plaque (NCP) or mixed plaque (MP), and NCP/MP in ≥2 segments were independent predictors of adverse cardiac events; however, the presence of calcified plaque (CP) was not. Conventional CCTA findings, including CACS ≥400 and a plaque ≥50% DS, demonstrated incremental prognostic value over clinical risk factors and SPECT (χ² 54.19 to 101.03; p <0.001). Addition of NCP/MP in ≥2 segments resulted in further significantly improved prediction (χ² 101.03 to 113.29; p <0.001).
CONCLUSION Comprehensive CCTA evaluation of coronary atherosclerosis provides independent and incremental prognostic value in relation to SPECT evaluation of myocardial ischemia. Specifically, segmentally-analyzed plaque composition with CCTA provides further risk stratification in addition to CACS and DS.
PubMed IF 2.8 순환기내과

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