SCI 발표논문

전체 4,588편

11682013

제1저자 박경우 · 교신저자 김효수

, , , , , , , , , , , , ,
Paraoxonase 1 gene polymorphism does not affect clopidogrel response variability but is associated with clinical outcome after PCI.
PLoS One. 2013;8(2):e52779.

Abstract
BACKGROUND Paraoxonase (PON) is a high-density-lipoprotein (HDL) associated enzyme with antioxidative and anti-atherogenic property. Its function is associated with coronary artery disease and its activity genetically controlled. We evaluated whether genetic variation of PON-1 is associated with clinical outcome in a large cohort of Korean patients with drug-eluting stents implantation.
METHODS A total of 1676 patients with drug-eluting stent implantation were enrolled in the prospective CROSS-VERIFY cohort from June 2006 to June 2010. We genotyped the PON1-Q192R gene, measured clopidogrel on-treatment platelet reactivity (OPR), and analyzed lipid profiles. The primary endpoint was the composite of cardiac death, myocardial infarction, and stent thrombosis at 12 months.
RESULTS PON-1 genotyping data were available in 1336 patients. Since the Q-allele is associated with decreased PON-activity, we analyzed the outcome between patients with QQ/QR (815 patients, 61%) and those with RR-genotype (521 patients, 39%). After adjustment for common cardiac risk factors, the QQ/QR-genotype was an independent predictor of the primary thrombotic endpoint with an 11-fold increased risk (HR 11.6, 95% CI: 1.55-87.0), but not repeat revascularization (HR 1.12, 95% CI: 0.78-1.61). The QQ/QR-genotype was not associated with OPR (QQ/QR: 231±86 PRU vs. RR 236±82 PRU, p = 0.342) but higher small-dense LDL levels (1.20±0.12 mg/dL vs. 0.76±0.15 mg/dL, p = 0.027). The increased risk of thrombotic outcomes was more profound in acute coronary syndrome (ACS) patients compared with non-ACS patients.
CONCLUSION PON1 Q-allele is an independent predictor of worse cardiovascular outcome independent of platelet function and is associated with significantly higher levels of small dense LDL-C.
PubMed IF 2.8 순환기내과
11672013

제1저자 박진주, 박경우 · 교신저자 김효수

, , , , , , , , , , , , , , ,
Genetic determinants of clopidogrel responsiveness in Koreans treated with drug-eluting stents.
Int J Cardiol. 2013;163(1):79-86.

Abstract
BACKGROUND Variations of genes encoding cytochrome enzymes, drug transporters, and paraoxonase have recently been reported to be associated with clopidogrel response variability besides the well-known CYP2C19 loss-of-function (LOF) alleles. We determined whether newly reported genetic variations are associated with clopidogrel on-treatment platelet reactivity (OPR) in Korean patients.
METHODS OPR was measured in 1264 consecutive patients who underwent percutaneous coronary intervention using the VerifyNowP2Y12 assay system and genotyping of PON-1 Q192R, ABCB1 C3435T, CYP1A2*1F, CYP2B6*6, CYP2C19*2, CYP2C19*3, CYP2C19*17, CYP3A4 (IVS10+12G>A), and CYP3A5*3 was performed. We applied two different cutoffs, i.e. 240 P2Y12 reaction units (PRU) and 253 PRU, to define high OPR.
RESULTS Mean OPR of the entire population was 231±83 PRU. Genetic variations of ABCB1 and PON-1 genes as well as that of CYP1A2, 2B6, 3A4, and 3A5 were not associated with clopidogrel response variability. As for CYP2C19, patients were classified into 4 metabolism genotypes: 0.6% ultrarapid (UM), 40.3% extensive (EM), 48.8% intermediate (IM), and 10.3% poor metabolizers (PM). After adjustment for possible confounders, CYP2C19 metabolism genotype was associated with a significant increase in OPR: effect on OPR-difference: +27 PRU, p=0.015 for EM, +53 PRU, p<0.001 for IM, and +74 PRU, p=0.006 for PM compared with UM. In multivariable analysis, the CYP2C19 genotype was the only independent predictor of high-OPR among genetic variations using two different cutoffs.
CONCLUSIONS Among genes postulated to be involved in clopidogrel metabolism, only the CYP2C19 genotype is associated with response variability and emerged as an independent predictor of high-OPR using two different cutoffs. PON-1 and ABCB1 genetic variants do not affect clopidogrel OPR in Korean patients.
PubMed IF 3.3 순환기내과
11662013

제1저자 박경우 · 교신저자 김효수

, , , , , , , , , , , , , , ,
CYP3A4 genetic status may be associated with increased vulnerability to the inhibitory effect of calcium-channel blockers on clopidogrel.
Circ J. 2013;77(5):1289-96.

Abstract
BACKGROUND Calcium-channel blockers (CCBs) inhibit the CYP3A4 enzyme, which is involved in clopidogrel activation. Studies have shown conflicting results regarding the effect of concomitant CCB administration on clopidogrel response. We investigated the relationship between CYP3A4 genotype and the inhibitory effect of CCBs on clopidogrel response.
METHODS AND RESULTS Clopidogrel on-treatment platelet reactivity (OPR) was measured and CYP3A4 (IVS10+12G>A) genotyped in 1,247 consecutive patients with drug-eluting stent implantation. The mean OPR was 231±83 (P2Y12 reaction units: PRU). In total, 332 (26.6%) CCB users had higher OPR compared with 915 (73.4%) non-CCB users (245±84 vs. 227±83 PRU, P=0.001). The distribution of CYP3A4 (IVS10+12G>A) genotype was 63.6%, 32.6% and 3.8% for GG, GA and AA genotypes, respectively. After adjustment for possible confounding factors, the number of A-alleles was associated with increased vulnerability to CCB use (effect of CCB use ΔPRU: +8 PRU, P=0.210, +24 PRU, P=0.012, +50 PRU, P=0.025, for patients with 0, 1, and 2 A-alleles, respectively, +24 PRU, P=0.005 for GA/AA genotypes). Furthermore, only in the GA/AA-genotype did CCB use result in a significantly increased risk for high-OPR (odds ratio 1.84, 95% confidence interval 1.15-2.92, P=0.010).
CONCLUSIONS CCB use is associated with increased OPR. The number of CYP3A4 (IVS10+12G>A) A-alleles may be associated with an increased vulnerability to the effects of CCBs on clopidogrel response variation.
PubMed IF 5.8 순환기내과
11652013

제1저자 박상돈/윤창환 · 교신저자 채인호

, , , , , , ,
Comparison of a drug-eluting balloon first and then bare metal stent with a drug-eluting stent for treatment of de novo lesions: study protocol of a randomized controlled trial.
Trials. 2013;14:38.

Abstract
BACKGROUND The use of a drug-eluting balloon for the treatment of de novo coronary artery lesions remains to be evaluated. A previous trial in patients with stable and unstable angina comparing a bare metal stent mounted on a drug-eluting balloon with a sirolimus-eluting stent failed to meet the prespecified non-inferiority criteria versus the sirolimus-eluting stent. The stent struts of a bare metal stent pre-mounted on a drug-eluting balloon may prevent the appropriate delivery of drugs to the vessel wall and may result in reduced efficacy. In the present study we will therefore evaluate the efficacy of a drug-eluting balloon for treating de novo coronary artery lesions using a strategy designed to uniformly deliver drug to the vessel with a bare metal stent.
METHODS/DESIGN The Comparison of Drug-Eluting Balloon first study is a prospective, randomized, open-label trial designed to demonstrate the non-inferiority of first using a drug-eluting balloon (Sequent please; B. Braun, Melsungen, Germany) followed by a bare metal stent (Coroflex Blue; B. Braun) compared with using a drug-eluting stent (Resolute Integrity; Boston Scientific, Natick, MA, USA) for de novo coronary artery lesions. The primary endpoint of the study is in-segment late loss at 9 months measured by quantitative coronary angiography. Secondary endpoints include angiographic findings such as angiographic success, device success, binary angiographic restenosis, and clinical outcomes such as procedural success, all-cause death, myocardial infarction, target vessel revascularization, target lesion revascularization, and stent thrombosis. A total of 180 patients will be enrolled in the study.
DISCUSSION The Comparison of Drug-Eluting Balloon first study will evaluate the clinical efficacy, angiographic outcomes and safety of a drug-eluting balloon first followed by a bare metal stent compared with a drug-eluting stent for the treatment of de novo coronary artery lesions.
TRIAL REGISTRATION Clinical Trials.gov: NCT01539603.
PubMed IF 2.1 순환기내과
11642013

제1저자 조선욱 · 교신저자 박영주

, , , , , , , , , , ,
Dickkopf-1 inhibits thyroid cancer cell survival and migration through regulation of β-catenin/E-cadherin signaling.
Mol Cell Endocrinol. 2013;366(1):90-8.

Abstract
Wnt/β-catenin signaling plays a role in tumorigenesis of human papillary thyroid cancer (PTC). Dickkopf-1 (Dkk-1) is an inhibitor of Wnt/β-catenin signaling. We investigated the therapeutic potential of Dkk-1 in human PTC cell lines, SNU-790, B-CPAP, and BHP10-3. Dkk-1 reversed the aberrant expression of β-catenin from nucleus to membrane and inhibited basal levels of TCF/LEF-dependent transcriptional activities. Furthermore, Dkk-1 inhibited cell viability in a dose-dependent manner and adenoviral transduction of constitutively active β-catenin blocked these effects, thus suggesting that the Dkk-1 anti-tumoral effect is mediated by Wnt/β-catenin signaling. Bromodeoxyuridine assay showed minimal effects of Dkk-1 on cell proliferation. Flow cytometric analysis with Annexin V staining showed marked induction of cell apoptosis by Dkk-1 treatment. Dkk-1 also restored the loss of membranous E-cadherin expression with consequent inhibition of cell migration and invasion. In conclusion, Dkk-1 inhibited the survival and migration of human PTC cells by regulating Wnt/β-catenin signaling and E-cadherin expression.
PubMed IF 3.4 내분비대사내과
11632013

제1저자 박경우 · 교신저자 김효수

, , , , , , , , , , , , , , , ,
Safety and efficacy of second-generation everolimus-eluting Xience V stents versus zotarolimus-eluting resolute stents in real-world practice: patient-related and stent-related outcomes from the multicenter prospective EXCELLENT and RESOLUTE-Korea registries.
J Am Coll Cardiol. 2013;61(5):536-44.

Abstract
OBJECTIVES This study sought to compare the safety and efficacy of the Xience V/Promus everolimus-eluting stent (EES) (Abbott Vascular, Temecula, California) with the Endeavor Resolute zotarolimus-eluting stent (ZES-R) (Medtronic Cardiovascular, Santa Rosa, California) in "all-comer" cohorts.
BACKGROUND Only 2 randomized controlled trials have compared these stents.
METHODS The EXCELLENT (Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting) and RESOLUTE-Korea registries prospectively enrolled 3,056 patients treated with the EES and 1,998 patients treated with the ZES-R, respectively, without exclusions. Stent-related composite outcomes (target lesion failure [TLF]) and patient-related composite outcomes were compared in crude and propensity score-matched analyses.
RESULTS Of 5,054 patients, 3,830 (75.8%) had off-label indication (2,217 treated with EES and 1,613 treated with ZES-R). The stent-related outcome (82 [2.7%] vs. 58 [2.9%], p = 0.662) and the patient-related outcome (225 [7.4%] vs. 153 [7.7%], p = 0.702) did not differ between EES and ZES-R, respectively, at 1 year, which was corroborated by similar results from the propensity score-matched cohort. The rate of definite or probable stent thrombosis (18 [0.6%] vs. 7 [0.4%], p = 0.306) also was similar. In multivariate analysis, off-label indication was the strongest predictor of TLF (adjusted hazard ratio: 2.882; 95% confidence interval: 1.226 to 6.779; p = 0.015).
CONCLUSIONS In this robust real-world registry with unrestricted use of EES and ZES-R, both stents showed comparable safety and efficacy at 1-year follow-up. Overall incidences of TLF and definite stent thrombosis were low, even in the patients with off-label indication, suggesting excellent safety and efficacy of both types of second-generation drug-eluting stents.
PubMed IF 22.3 순환기내과
11622013

제1저자 박영식 · 교신저자 유철규

, , , , , , , , ,
Clinical implication of protease-activated receptor-2 in idiopathic pulmonary fibrosis.
Respir Med. 2013;107(2):256-62.

Abstract
Idiopathic pulmonary fibrosis (IPF) is a lethal pulmonary disease which is characterized by progressive fibrosis. In general, the exaggerated activation of the coagulation cascade has been observed during initiation or maintenance of the fibrotic disease. In a recent study, protease-activated receptor (PAR)-2, which plays a key role in coagulation cascade, was up-regulated in IPF patients, however, its clinical implications have not been understood. The objective of the present study was to evaluate the clinical significance of PAR-2 expression in the alveolar epithelial cells of IPF patients. PAR-2 expression was evaluated by immunohistochemical method in formalin-fixed and paraffin-embedded tissues of surgical lung biopsies from patients with IPF. Fibrosis scores from hematoxylin and eosin-stained lung sections and honeycombing scores in chest CT were calculated. Medical records were retrospectively reviewed and the correlation between the expression of PAR-2 and clinical profiles were assessed. Among thirty-three IPF patients, PAR-2 expression was observed in 25 (75.8%). The lymphocyte counts in peripheral blood (2317 vs. 1753, p = 0.044) and honeycombing scores in chest CT (4.0 vs. 3.0 p = 0.046) were higher in PAR-2 positive group compared with PAR-2 negative group. During a follow-up duration of median 40.3 months, 7 (21.2%) patients died and they were all included in the PAR-2 positive group (p = 0.113). We conclude that PAR-2 is expressed in the alveolar epithelial cells of a substantial number of IPF patients, and the expression of PAR-2 significantly correlates with the extent of honeycombing shown in chest CT.
PubMed IF 3.3 호흡기내과
11612013

제1저자 이승표 · 교신저자 손대원

, , , ,
Apically displaced papillary muscles mimicking apical hypertrophic cardiomyopathy.
Eur Heart J Cardiovasc Imaging. 2013;14(2):128-34.

Abstract
AIMS Apical hypertrophic cardiomyopathy (ApHCM) is a subtype of hypertrophic cardiomyopathy, which is clinically suspected by a characteristic giant negative T (GNT) wave on electrocardiogram (ECG) and diagnosed by demonstrating apical hypertrophy on ECG. However, GNT may not always be specific for ApHCM as in this report of apically displaced papillary muscle (ADPM).
METHODS AND RESULTS By retrospectively collecting 12-lead ECGs with a GNT wave and apical hypertrophy on 2D-ECG from 2008 to 2010, we identified 55 patients with both of these findings. ADPM was defined to be present when the base of the papillary muscle originated from the apical one-third of the left ventricle. A diagnosis of ApHCM in patients with apical hypertrophy but without evidence of ADPM was given otherwise. Careful evaluations of 2D-ECGs suggested that 20% (11/55) of all patients had an ADPM mimicking ApHCM. Baseline clinical and echocardiography data were not different between the two except for the maximal T wave on 12-lead ECG and apicoseptal hypertrophy, suggesting that the differentiation of these two groups may be subtle and difficult. In addition, patients with ADPM frequently showed abnormal insertion of papillary muscle into the left ventricular outflow tract or into the base of mitral valve leaflet.
CONCLUSION These findings suggest that ADPM may also be present with GNT on 12-lead ECG and emphasizes the careful evaluation of the left ventricular apex for proper diagnosis and discrimination of ApHCM.
PubMed IF 6.1 순환기내과
11602013

제1저자 김은정 · 교신저자 허대석

, , , , ,
Ex vivo activation and expansion of natural killer cells from patients with advanced cancer with feeder cells from healthy volunteers.
Cytotherapy. 2013;15(2):231-241.e1.

Abstract
BACKGROUND AIMS Culturing natural killer (NK) cells from patients with advanced cancer is difficult and has restricted the generation of sufficient cell numbers for autologous adoptive NK-cell therapy. The aim of this study was to establish a novel method for ex vivo NK-cell expansion from patients with cancer.
METHODS NK cells (CD3(-)CD56(+)) were isolated from peripheral blood mononuclear cells from healthy volunteers and cancer patients, and NK(-) fractions were used as feeder cells. Purified NK cells were co-cultured with feeder cells in AIM-V medium (Invitrogen, Carlsbad, CA, USA) supplemented with 5% human serum and 1000 units/mL human interleukin-2.
RESULTS NK cells co-cultured with feeder cells from healthy volunteers (feeder-HV) expanded more than NK cells co-cultured with feeder cells from cancer patients (feeder-CP). During the 14-day culture period, NK cells from patients with advanced cancer co-cultivated with feeder-HV expanded on average 300-fold. NK cells co-cultivated with feeder-CP expanded on average 169.4-fold. Cultures grown in the presence of feeder-HV contained 93.8 ± 7.0% (mean ± standard deviation; n = 6) CD3(-)CD56(+) NK cells, and cultures grown in the presence of feeder-CP contained 83.6 ± 15.9% CD3(-)CD56(+) NK cells. Feeder-HV caused a relative increase in CD3(+)CD4(+) T cells, whereas feeder-CP did not induce changes. Interleukin-15, a cytokine that induces NK-cell proliferation, was detected in the culture supernatants of feeder-HV but not in those of feeder-CP.
CONCLUSIONS Feeder cells obtained from healthy volunteers have the potential to expand and activate NK cells from patients with advanced cancer. The novel NK-cell expansion method described here provides a technique for acquiring the large numbers of highly active NK cells from patients with cancer for autologous adoptive immunotherapy.
PubMed IF 4.5 혈액종양내과
11592013

제1저자 박경우 · 교신저자 김효수

, , , , , , , , , , , , , , ,
Safety and efficacy of everolimus- versus sirolimus-eluting stents: a systematic review and meta-analysis of 11 randomized trials.
Am Heart J. 2013;165(2):241-50.e4.

Abstract
BACKGROUND While EES have proven superior to paclitaxel-eluting stents, it remains uncertain whether EES improve clinical outcomes compared to SES, which are the most efficacious among the first-generation drug-eluting stents. We performed a meta-analysis of randomized trials comparing the efficacy and safety of everolimus-eluting stents (EES) versus sirolimus-eluting stents (SES) in patients undergoing percutaneous coronary intervention.
METHODS From online and offline search until December 2011, we identified 11 randomized trials (total 12,869 patients). The primary endpoint was major adverse cardiac events.
RESULTS The risk of major adverse cardiac events did not differ significantly between the patients treated with EES versus SES [OR, 0.90 (95% CI, 0.77-1.04); P = .162]. However, we found a significant reduction in the risk of repeat revascularization in the EES arm [OR, 0.85 (95% CI, 0.71-1.00); P = .047]. There were no significant differences regarding the risk of cardiac death [OR, 0.97 (95% CI, 0.74-1.27); P = .834], or myocardial infarction [OR, 0.95 (95% CI, 0.75-1.20), P = .656]. The risk of definite or probable stent thrombosis tended to be lower [OR, 0.68 (95% CI, 0.45-1.02); P = .065], while definite ST was significantly lower [OR, 0.44 (95% CI, 0.25-0.80); P = .007] with EES.
CONCLUSIONS In a large systematic overview of comparative trials involving percutaneous revascularization with drug-eluting stents, treatment with EES significantly reduced the risk of repeat revascularization and definite ST compared to SES. We found no significant differences in the risk of cardiac death or myocardial infarction.
PubMed IF 3.4 순환기내과
11582013

제1저자 이정환 · 교신저자 주권욱

, , , , , , , , ,
Rapid correction rate of hyponatremia as an independent risk factor for neurological complication following liver transplantation.
Tohoku J Exp Med. 2013;229(2):97-105.

Abstract
Hyponatremia is prevalent before liver transplantation and generally corrected immediately after transplantation. However, the clinical significance of correction rate of hyponatremia is not well investigated. The prognostic impact of pre-transplant serum sodium concentrations and post-transplant correction rate of hyponatremia were assessed. A total of 512 patients who received orthotopic liver transplants were enrolled. The correction rate of hyponatremia (delta sodium, ΔNa) was calculated based on the data collected during the first 48 hours following liver transplantation. Outcomes, including in-hospital mortality, delirium, neurological complications, acute kidney injury, and infections, were compared according to the serum sodium levels (sNa < 125, 125-135, and ≥ 135 mmol/L), and the risk factors for in-hospital mortality and neurological complications were analyzed using multivariate logistic regression methods. Patients with severe hyponatremia (sNa < 125 mmol/L) had higher rates of in-hospital mortality (9.6%, P = 0.010), delirium (54.8%, P = 0.003), neurological complications (24.7%, P = 0.003), and acute kidney injury (57.5%, P = 0.005). In multivariate analysis, serum sodium levels (OR = 0.975, P = 0.402) and delta sodium (OR = 1.097, P = 0.066) were not independent risk factors for in-hospital mortality. However, delta sodium (OR = 1.093, P = 0.003) and fast correction rate of hyponatremia (ΔNa ≥ 12 mmol/L/24h, OR = 3.397, P = 0.023) were significantly associated with post-transplant neurological complications. Pre-transplantation hyponatremia was not independently associated with clinical outcomes. However, rapid correction of hyponatremia is an independent risk factor for the development of post-transplant neurological complications.
PubMed IF 1.5 신장내과
11572013

제1저자 김효철, 이정훈 · 교신저자 정진욱

, , , , , , , ,
Transarterial chemoembolization with additional cisplatin infusion for hepatocellular carcinoma invading the hepatic vein.
J Vasc Interv Radiol. 2013;24(2):274-83.

Abstract
PURPOSE To evaluate retrospectively the efficacy of transarterial chemoembolization in patients with hepatocellular carcinoma (HCC) with hepatic vein invasion by comparing the results of conventional transarterial chemoembolization and modified transarterial chemoembolization.
MATERIALS AND METHODS From January 2000 to December 2009, 107 patients with HCC and hepatic vein invasion and Child-Pugh class A were treated by transarterial chemoembolization. Modified transarterial chemoembolization (conventional transarterial chemoembolization followed by additional infusion of 50-100 mg of cisplatin) has been undertaken since 2005. Clinical and radiologic data were reviewed and analyzed retrospectively. The overall survival rates were obtained by the Kaplan-Meier method and compared by the log-rank test.
RESULTS Conventional transarterial chemoembolization was performed in 60 patients, and modified transarterial chemoembolization was performed in 47 patients. No significant differences were observed in major complications between the groups. The median survival was longer in the modified group compared with the conventional group (9.7 mo, 95% confidence interval [CI], 4.3-15.1, vs 6.7 mo, 95% CI, 4.8-8.5; P = .047). By subgroup analysis, modified transarterial chemoembolization increased survival of patients with a diffuse tumor type (8.9 mo, 95% CI, 5.9-11.9, vs 3.8 mo, 95% CI, 2.5-5.0; P = .000) and patients without metastasis (20.9 mo, 95% CI, 12.2-29.5, vs 7.3 mo, 95% CI, 4.1-10.5; P = .005). Multivariate analysis identified three independent predictive factors for mortality: diffuse tumor type (P = .001), metastasis (P = .009), and modified transarterial chemoembolization protocol (P = .003).
CONCLUSIONS A survival benefit was suggested with transarterial chemoembolization with additional cisplatin infusion over conventional transarterial chemoembolization in patients with HCC invading the hepatic vein.
PubMed IF 3.1 소화기내과
11562013

제1저자 민보영 · 교신저자 김진욱

, , , , , , , , , ,
Ethanol potentiates hepatitis B virus replication through oxidative stress-dependent and -independent transcriptional activation.
Biochem Biophys Res Commun. 2013;431(1):92-7.

Abstract
Excessive alcohol intake accelerates disease progression in chronic hepatitis B virus (HBV) infection, but the mechanisms by which ethanol worsens the prognosis of chronic hepatitis B (CHB) are not fully understood. The aim of this study was to investigate whether HBV replication is augmented by alcohol or alcohol-induced cytochrome p450 2E1 (CYP2E1), and if so, whether oxidative stress is involved in the process. Ethanol treatment promoted HBV replication in HepAD38 cells that permit the conditional viral replication. Luciferase reporter assays confirmed that HBV core, preS1 and preS2/S promoter activities were augmented by ethanol. Ethanol did not induce oxidative stress in HepAD38 cells with minimal expression of CYP2E1. However, over-expression of CYP2E1 induced oxidative stress and amplified transcriptional activation of HBV by ethanol. Antioxidant glutathione treatment attenuated CYP2E1-mediated augmentation of HBV replication in ethanol-treated cells. In conclusion, ethanol enhances transcriptional activity of HBV promoters in human hepatoma cells in an oxidative stress-independent manner; and CYP2E1-mediated oxidative stress potentiates the ethanol-induced transactivation of HBV.
PubMed IF 2.5 소화기내과
11552013

제1저자 김광일 · 교신저자 진호준

, , , , , , , ,
Differential white blood cell count and all-cause mortality in the Korean elderly.
Exp Gerontol. 2013;48(2):103-8.

Abstract
The circulating white blood cell (WBC) count has been considered a good biomarker of systemic inflammation, but the predictive value of this inexpensive and universally obtained test result has not been fully explored in the elderly. The objective of this study was to assess the independent association of WBC count and its individual components with mortality in an elderly population. We studied a total of 9996 participants (age ≥65 years) who underwent routine health examinations at the 2 healthcare centers affiliated with Seoul National University. Mortality data were obtained from the National Statistics Office of Korea. The mean age of the study population was 69.7 (SD 4.3) years, and 5491 of the subjects (54.9%) were male. The median length of follow-up was 44.9 months (range, 1.2-78.7 months). There were 118 deaths (1.2%) during the follow-up period. The leading cause of death was cancer. Compared with the survivors, the deceased subjects were older, predominantly male, had increased levels of inflammatory markers, and had poor nutritional status. A significant difference in mortality was identified among patients in different WBC and WBC subtype quartile groups. Cox proportional hazards analysis indicated that monocyte count (HR: 5.18, 95% CI: 2.44-11.02) was a strongest predictor of all-cause mortality than total WBC count (HR: 1.57, 95% CI: 0.88-2.80), granulocyte count (HR: 2.11, 95% CI: 1.15-3.88), and lymphocyte count (HR: 1.11, 95% CI: 0.66-1.86), even after adjusting for possible confounding variables. Monocyte counts were associated with an increased risk of cardiovascular and cancer-related mortality in the elderly population. In conclusion, the total WBC count is an independent predictor of mortality in older adults, but the monocyte subtype provides greater predictive ability.
PubMed IF 5.1 신장내과
11542013

제1저자 김경임, 김지원 · 교신저자 윤성수, 오정미

, , , , , , , , , ,
Recombinant human epidermal growth factor on oral mucositis induced by intensive chemotherapy with stem cell transplantation.
Am J Hematol. 2013;88(2):107-12.

Abstract
Oral mucositis (OM) is one of the most common and debilitating complications in patients undergoing intensive chemotherapy followed by hematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) oral spray for OM induced by intensive chemotherapy followed by HSCT. Patients were randomly assigned to either the rhEGF group or placebo group. The severity of OM and self-reported quality of life (QOL) were assessed daily. A total of 58 patients were analyzed. Baseline characteristics were similar between the two groups. The incidence of NCI grade ≥ 2 OM was higher in the rhEGF group (78.6% vs. 50%, P = 0.0496). However, the duration of OM in patients with NCI grade ≥ 2 tended to be shorter in the rhEGF group (8.5 days vs. 14.5 days, P = 0.262). The QOL analysis in patients with World Health Organization (WHO) grade ≥ 3 OM showed that rhEGF significantly reduced limitations in swallowing (P = 0.039) and drinking (P = 0.042). The duration of hospitalization (P = 0.047), administration of total parenteral nutrition (P = 0.012), and the usage of opioid analgesics (P = 0.018) were significantly shorter in the rhEGF group with WHO grade ≥ 3 OM. Adverse events were mild and similar between the two groups. In conclusion, this analysis showed that rhEGF did not reduce the incidence of NCI grade ≥ 2 OM. However, the patients with WHO grade ≥ 3 OM in the rhEGF group showed better results compared to the placebo group for several secondary endpoints.
PubMed IF 9.4 혈액종양내과
11532013

제1저자 김도형 · 교신저자 이정표

, , , , , , , ,
Early referral to a nephrologist improved patient survival: prospective cohort study for end-stage renal disease in Korea.
PLoS One. 2013;8(1):e55323.

Abstract
The timing of referral to a nephrologist may influence the outcome of chronic kidney disease patients, but its impact has not been evaluated thoroughly. The results of a recent study showing an association between early referral and patient survival are still being debated. A total of 1028 patients newly diagnosed as end-stage renal disease (ESRD) from July 2008 to October 2011 were enrolled. Early referral (ER) was defined as patients meeting with a nephrologist more than a year before dialysis and dialysis education were provided, and all others were considered late referral (LR). The relationship of referral pattern with mortality in ESRD patients was explored using a Cox proportional hazards regression models. Time from referral to dialysis was significantly longer in 599 ER patients than in 429 LR patients (62.3 ± 58.9 versus 2.9 ± 3.4 months, P<0.001). Emergency HD using a temporary vascular catheter was required in 485 (47.2%) out of all patients and in 262 (43.7%) of ER compared with 223 (52.0%) of LR (P = 0.009). After 2 years of follow-up, the survival rate in ER was better than that in LR (hazard ratio [HR] 2.38, 95% confidence interval [CI] 1.27-4.45, P = 0.007). In patients with diabetes nephropathy, patient survival was also significantly higher in ER than in LR (HR 4.74, 95% CI 1.73-13.00, P = 0.002). With increasing age, HR also increased. Timely referral to a nephrologist in the predialytic stage is associated with reduced mortality.
PubMed IF 2.8 신장내과
11522013

제1저자 이하정 · 교신저자 허남주

, , , , , ,
Potassium intake and the prevalence of metabolic syndrome: the Korean National Health and Nutrition Examination Survey 2008-2010.
PLoS One. 2013;8(1):e55106.

Abstract
Lower potassium intake is considered to be correlated with diabetes incidence. However, few studies have investigated the effect of potassium intake on metabolic syndrome (MetS). Data was taken from the Korean National Health and Nutritional Examination Survey (2008-2010) using weighted adjustment. MetS was defined as per the revised National Cholesterol Education Program criteria. Homeostasis model assessment indices were calculated to diagnosis insulin resistance (IR). A total of 16,637 participants (44 ± 0.25 years) were included. Women ingested lower amounts of potassium (2.71 ± 0.02 g/day) than men (3.45 ± 0.03 g/day). A curvilinear association between potassium intake and MetS prevalence was found among women. Women with less than the Adequate Intake (4.7 g/day) of potassium had an 11% risk reduction for MetS (adjusted odds ratio [OR], 0.89; 95% confidence interval [CI], 0.82-0.96; P = 0.004) and a 10% risk reduction for IR (OR, 0.90; 95% CI, 0.82-0.99; P = 0.026) for every 1 g/day potassium increase. Compared with the reference group (3.5-4.5 g/day), potassium intake was inversely associated with an increased risk of MetS (1.5-2.5 g/day; OR, 1.29; 95% CI, 1.02-1.63; P = 0.035; <1.5 g/day; OR, 1.40; 95% CI, 1.06-1.85; P = 0.017) and IR (<1.5 g/day; OR, 1.36; 95% CI, 1.05-1.76; P = 0.021). This relationship was more prominent in postmenopausal women, but not observed among men. Higher potassium intake is significantly associated with a lower MetS prevalence in women, and IR is believed to be connected.
PubMed IF 2.8 신장내과
11512013

제1저자 이하정 · 교신저자 진호준

, , , , , , ,
Mortality and renal outcome of primary glomerulonephritis in Korea: observation in 1,943 biopsied cases.
Am J Nephrol. 2013;37(1):74-83.

Abstract
BACKGROUND Previous epidemiological studies have focused on the prevalence of primary glomerulonephritis (GN), but few have explored long-term patient outcomes. This study was conducted to investigate the long-term patient and renal outcomes of primary GN.
METHODS A total of 1,943 biopsy-proven primary GN patients were included. The outcomes were mortality and end-stage renal disease (ESRD) progression. The relative mortality rate was expressed by the standardized mortality ratio (SMR) and the 95% confidence interval (CI).
RESULTS During the median follow-up of 90 months, 325 (16.7%) patients progressed to ESRD and 164 (8.4%) patients died. Patients with minimal change disease exhibited the best renal and patient outcomes, whereas those with membranoproliferative GN had the worst. IgA nephropathy patients appeared to have a good survival rate in spite of their considerable progression to ESRD, and focal segmental glomerulosclerosis patients showed poor renal and patient outcomes. Mortality was 67% higher in primary GN patients than in the age- and sex-matched general population (SMR, 1.67; 95% CI, 1.42-1.95). The difference was more prominent in women (SMR, 2.95; 95% CI, 2.27-3.77) than in men (SMR, 1.31; 95% CI, 1.07-1.60). Renal risk factors, e.g. hypertension, proteinuria and initial renal dysfunction, were all associated with higher mortality, and the relative mortality rate increased with the number of risk factors.
CONCLUSIONS In patients with primary GN, mortality is significantly higher than in the age-/sex-matched general population, especially in women. Moreover, the presence of renal risk factors is positively associated with both relative mortality and progression to ESRD.
PubMed IF 3.8 신장내과
11502013

제1저자 명선정 · 교신저자 박완범

, , , ,
Effect of enhanced analytic reasoning on diagnostic accuracy: a randomized controlled study.
Med Teach. 2013;35(3):248-50.

Abstract
BACKGROUND Diagnostic error can be caused by several types of cognitive bias, which may be reversed by enhancing analytic reasoning.
AIMS To evaluate whether enhancing analytic reasoning can increase diagnostic accuracy in objective structured clinical examination (OSCE) in medical students.
METHODS All fourth-year medical students, randomly assigned to the analytic reasoning or control groups, undertook the OSCE with four cases using standardized patients. The analytic reasoning group was requested to list differential diagnoses and findings compatible or not compatible with each diagnosis prior to providing a diagnosis, while the control group provided a diagnosis without these processes. Mean diagnostic accuracy scores (perfect score, 4.0) from four cases of OSCE were compared between the two groups.
RESULTS One hundred forty-five students were randomly assigned to the analytic reasoning group (n = 65) or the control group (n = 80). The baseline characteristics, including grade point average and the scores from each patient encounter, were comparable between groups. Mean diagnostic accuracy scores were significantly higher in the analytic reasoning group than in the control group (3.40 ± 0.66 versus 3.05 ± 0.98; p = 0.011).
CONCLUSION Enhancement of analytic reasoning may improve diagnostic accuracy in novice doctors.
PubMed IF 4 소화기내과
11492013

제1저자 김정목 · 교신저자 김주성

, , , , , , ,
The guggulsterone derivative GG-52 inhibits NF-κB signaling in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice.
Am J Physiol Gastrointest Liver Physiol. 2013;304(2):G193-202.

Abstract
Gastric mucosal inflammation can develop after challenge with noxious stimuli such as alcohol. Specially, alcohol stimulates the release of inflammatory cytokines but does not increase gastric acid secretion, leading to gastric mucosal damage. The plant sterol guggulsterone and its novel derivative GG-52 have been reported to inhibit nuclear factor-κB (NF-κB) signaling in intestinal epithelial cells and experimental colitis. In the present study, we investigated the anti-inflammatory effects of GG-52 on gastric epithelial cells and on ethanol-induced gastric mucosal inflammation in mice. GG-52 inhibited the expression of interleukin-8 (IL-8) in gastric epithelial AGS and MKN-45 cell lines stimulated with tumor necrosis factor (TNF)-α in a dose-dependent manner. Pretreatment with GG-52 suppressed TNF-α-induced activation of IκB kinase (IKK) and NF-κB signaling in MKN-45 cells. In contrast, the inactive analog GG-46 did not produce significant changes in IL-8 expression or NF-κB activation. In a model of ethanol-induced murine gastritis, administration of GG-52 significantly reduced the severity of gastritis, as assessed by macroscopic and histological evaluation of gastric mucosal damage. In addition, the ethanol-induced upregulation of chemokine KC, a mouse homolog of IL-8, and phosphorylated p65 NF-κB signals were significantly inhibited in murine gastric mucosa pretreated with GG-52. These results indicate that GG-52 suppresses NF-κB activation in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice, suggesting that GG-52 may be a potential gastroprotective agent.
PubMed IF 3 소화기내과
11482013

제1저자 김학령, 임문순 · 교신저자 조주희

, , , , , ,
The association between arterial stiffness and left ventricular filling pressure in an apparently healthy Korean population.
Cardiovasc Ultrasound. 2013;11(1):2.

Abstract
BACKGROUND The aim of this study is to investigate the association between arterial stiffness and left ventricular filling pressure in an apparently healthy Korean population.
METHODS A total of 115 healthy subjects without known cardiovascular risk factors or overt heart disease who underwent both transthoracic echocardiography and brachial-ankle pulse wave velocity (baPWV) measurement at the same day during their routine check-ups were analyzed.
RESULTS The mean age of study subjects was 52.8 ± 8.4 years, and 78 (67.8%) were men. The mean baPWV value was 1,325 ± 185 cm/s. Study subjects were divided into 3 groups according to E/E' value: subjects with E/E' < 8, 8-12.9 and E/E' ≥ 13. As E/E' increased, baPWV value increased gradually: baPWV in subjects with E/E' < 8, E/E' 8-12.9 and E/E' ≥ 13, were 1,261 ± 163, 1,345 ± 169, 1,569 ± 232 cm/s, respectively (p < 0.001). In multiple linear regression analyses, baPWV was significantly associated with E/E' (β = 0.371, p < 0.001) after controlling confounders including age, sex and body mass index. In receiver-operating characteristic (ROC) curve analysis, the sensitivity and specificity for detection of E/E' ≥ 10 were 78.6% and 59.8%, respectively with mean baPWV of 1,282 cm/s as the cut off value. The discriminatory capacity for predicting E/E' ≥ 10 was improved from an area under the ROC curve of 0.646 with age alone to 0.734 when baPWV was added (p < 0.001).
CONCLUSIONS There is a significant association between baPWV and E/E' in an apparently healthy Korean population. BaPWV is useful as a simple and non-invasive method for early detection of increased LV filling pressure among these people.
PubMed IF 2 순환기내과
11472013

제1저자 조소영 · 교신저자 김나영

, , , , , ,
Comparison of gastroesophageal reflux disease symptoms and proton pump inhibitor response using gastroesophageal reflux disease impact scale questionnaire.
J Neurogastroenterol Motil. 2013;19(1):61-9.

Abstract
BACKGROUND/AIMS To compare gastroesophageal reflux disease (GERD) symptoms and response to proton pump inhibitor (PPI) in patients with erosive esophagitis (EE), non-erosive reflux disease (NERD) or functional heartburn (FH) using GERD impact scale (GIS) questionnaire.
METHODS Total 126 patients with GERD symptoms were diagnosed as EE (n = 62), NERD (n = 34) and FH (n = 30) by endoscopy, 24-hour esophageal pH testing and Bernstein test, prospectively. Analysis of risk factors and GIS questionnaire for GERD symptoms and quality of life were performed before and 8 weeks after PPI treatment.
RESULTS EE group had a higher proportion of men, frequent alcohol consumption, smoking, hiatal hernia, body mass index ≥ 25 kg/m(2) and triglyceride levels (≥ 150 mg/dL) than the other groups (all P < 0.05). On the other hand, both psychiatric treatment and psychopharmacotherapy were more frequent in patients with FH than in those with EE and NERD (both P < 0.05). Among GERD symptoms, chest pain was more frequent in FH group than in EE and NERD groups (P < 0.05). Eating problems and limitation of productive daily activities occurred frequently in FH group and NERD group, respectively. GIS after 8 week PPI treatment showed improvement in all of the GERD symptoms in EE (all P < 0.05) and in acid regurgitation, epigastric pain and hoarseness in NERD group (all P < 0.05). In terms of quality of life, PPI treatment improved sleep disturbance in EE (P = 0.031) and limitation of productive activity in the NERD group (P = 0.001).
CONCLUSIONS GIS questionnaire showed that different characteristics and symptoms improved after PPI therapy among patients with EE, NERD and FH, demonstrating the usefulness of the GIS questionnaire.
PubMed IF 3.7 소화기내과
11462013

제1저자 정고은 · 교신저자 박민정

, , , , ,
Helicobacter pylori seropositivity in diabetic patients is associated with microalbuminuria.
World J Gastroenterol. 2013;19(1):97-102.

Abstract
AIM To investigate the relationship between Helicobacter pylori (H. pylori) seropositivity and the presence of microalbuminuria.
METHODS Between December 2003 and February 2010, asymptomatic individuals who visited the Seoul National University Healthcare System Gangnam Center for a routine check-up and underwent tests for H. pylori immunoglobulin G antibodies and urinary albumin to creatinine ratio (UACR) were included. All study subjects completed a structured questionnaire, anthropometric measurements and laboratory tests. Anti-H. pylori immunoglobulin G was identified using an enzyme-linked immunosorbent assay kit. A random single-void urine sample, collected using a clean-catch technique, was obtained to determine the UACR. The presence of microalbuminuria was defined as a UACR from 30 to 300 μg/mg. The presence of diabetes mellitus (DM) was defined as either a fasting serum glucose level greater than or equal to 126 mg/dL or taking anti-diabetic medication. Multiple logistic regression analysis was performed to identify the risk factors. The dependent variable was microalbuminuria, and the independent variables were the other study variables.
RESULTS A total of 2716 subjects (male, 71.8%; mean age, 54.9 years) were included. Among them, 224 subjects (8.2%) had microalbuminuria and 324 subjects (11.9%) had been diagnosed with DM. Subjects with microalbuminuria had a significantly higher H. pylori seropositivity rate than subjects without microalbuminuria (60.7% vs 52.8%, P = 0.024). Multivariate analysis after adjustment for age, body mass index (BMI), waist circumference, and glucose and triglyceride levels showed that H. pylori seropositivity was significantly associated with microalbuminuria [odds ratio (OR), 1.40, 95% CI, 1.05-1.89, P = 0.024]. After the data were stratified into cohorts by glucose levels (≤ 100 mg/dL, 100 mg/dL < glucose < 126 mg/dL, and ≥ 126 mg/dL or history of DM), H. pylori seropositivity was found to be significantly associated with microalbuminuria in diabetic subjects after adjusting for age, BMI and serum creatinine level (OR, 2.21, 95% CI, 1.20-4.08, P = 0.011). In addition, the subjects were divided into five groups. Those without microalbuminuria (an UACR of < 30 μg/mg) were divided into four groups in accordance with their UACR values, and subjects with microalbuminuria comprised their own group. Notably, H. pylori seropositivity gradually increased with an increase in UACR (P = 0.001) and was highest in subjects with microalbuminuria (OR, 2.41, 95% CI, 1.14-5.11). This suggests that H. pylori seropositivity is positively associated with microalbuminuria in diabetic subjects.
CONCLUSION H. pylori seropositivity was independently associated with microalbuminuria, and the prevalence of H. pylori seropositivity was associated with the severity of UACR in diabetic subjects.
PubMed IF 7.7 소화기내과
11452013

제1저자 김수정 · 교신저자 이근욱

, , , , , ,
Safety, compliance, and predictive parameters for dosage modification in adjuvant S-1 chemotherapy for gastric cancer.
Cancer Sci. 2013;104(1):116-23.

Abstract
This study was performed to investigate the compliance, safety, dosage modifications (dose reduction and/or schedule change [including permanent S-1 withdrawal]), and clinical parameters that predict S-1 dosage modification in gastric cancer patients receiving adjuvant S-1 chemotherapy. One hundred and forty-nine patients who underwent curative D2 surgery and received adjuvant S-1 chemotherapy were enrolled. S-1 was administered orally (40 mg/m(2) twice daily on days 1-28 every 6 weeks) for 1 year. For patients unable to tolerate S-1, the dosage was reduced or the schedule was changed to a 3-weekly schedule of 2 weeks on treatment followed by 1 week off treatment. The planned 1-year treatment was completed in 73.8% of patients; 69 patients required dosage modification because of toxicity. The most frequent cause of dosage modification was enterocolitis (37 patients; defined as ≥ grade 2 abdominal pain and/or ≥ grade 2 diarrhea). Most dosage modification occurred during the early cycles of treatment (within the first 3 months). Severe toxicities (≥ grade 3) included neutropenia (13.4%), abdominal pain (8.1%) and diarrhea (8.1%). In multivariate analyses, decreased relative dose intensity was related to poor disease-free survival independent of stage, and only low creatinine clearance predicted S-1 dosage modification. In conclusion, although adjuvant S-1 therapy has a high compliance rate, meticulous monitoring of adverse events is required in the early period of treatment. Decreased creatinine clearance was the only factor that predicted dosage modification. In patients with creatinine clearance <50 mL/min, dosage reduction should be considered from the initiation of S-1 treatment.
PubMed IF 4.9 혈액종양내과
11442013

제1저자 남현진 · 교신저자 오도연

, , , , , , , , , ,
Antitumor activity of saracatinib (AZD0530), a c-Src/Abl kinase inhibitor, alone or in combination with chemotherapeutic agents in gastric cancer.
Mol Cancer Ther. 2013;12(1):16-26.

Abstract
Src is a nonreceptor tyrosine kinase involved in the cross-talk and mediation of many signaling pathways that promote cell proliferation, adhesion, invasion, migration, and tumorigenesis. Increased Src activity has been reported in many types of human cancer, including gastric cancer. Therefore, this factor has been identified as a promising therapeutic target for cancer treatments, and targeting Src in gastric cancer is predicted to have potent effects. We evaluated the antitumor effect of a c-Src/Abl kinase inhibitor, saracatinib (AZD0530), alone or combined with chemotherapeutic agents in gastric cancer cell lines and a NCI-N87 xenograft model. Among 10 gastric cancer cell lines, saracatinib specifically inhibited the growth and migration/invasion of SNU216 and NCI-N87 cells. Saracatinib blocked the Src/FAK, HER family, and oncogenic signaling pathways, and it induced G(1) arrest and apoptosis in SNU216 and NCI-N87 cells. Apoptosis required induction of the proapoptotic BCL2 family member Bim. Knockdown of Bim using siRNA decreased apoptosis induced by treatment with saracatinib, suggesting that Bim has an important role in saracatinib-induced apoptosis. Saracatinib enhanced the effects of lapatinib, an EGFR/HER2 dual inhibitor, in SNU216 and NCI-N87 cells. Furthermore, combined treatment with saracatinib and 5-fluorouracil (5-FU) or cisplatin exerted synergistic effects in both saracatinib-sensitive and saracatinib-resistant cells. Consistent with our in vitro findings, cotreatment with saracatinib and 5-FU resulted in enhanced antitumor activity in the NCI-N87 xenografts. These data indicate that the inhibition of Src kinase activity by saracatinib alone or in combination with other agents can be a strategy to target gastric cancer.
PubMed IF 6.9 혈액종양내과
11432013

제1저자 임수 · 교신저자 Liguori Gary

, , , , , , ,
Changes in metabolic syndrome in American and Korean youth, 1997-2008.
Pediatrics. 2013;131(1):e214-22.

Abstract
BACKGROUND Metabolic syndrome (MetSyn) in children and adolescence is increasing worldwide; however, its pattern may be different between Asians and Americans. We compare the prevalence and patterns of MetSyn between American and Korean children and adolescents between roughly 1998 and 2007.
METHODS Data from the American and Korean versions of the NHANES (NHANES and KNHANES) were used for this study. The main outcome is prevalence and pattern of MetSyn among participants separately in each country. In each survey, stratified multistage probability sampling designs and weighting adjustments were conducted to represent the entire population. The revised National Cholesterol Education Program criteria were used to define MetSyn.
RESULTS Totals of 934, 1781, and 1690 Americans aged 12 to 19 participated in NHANES 1988-1994, NHANES 1999-2002, and NHANES 2003-2006, respectively; and 1225, 976, 705, and 456 Koreans aged 12 to 19 have participated in KNHANES 1998, 2001, 2005, and 2007. The age-adjusted prevalence of MetSyn in American NHANES decreased from 7.3% to 6.7% and 6.5%, whereas in Korean NHANES there was an increase from 4.0% to 5.9%, 6.6%, and 7.8% in each country's respective study. Increases in dyslipidemia and abdominal obesity contributed to the increased prevalence in Korea, whereas in the United States, decreases in low high-density lipoprotein cholesterolemia and high blood pressure contributed to a decreased prevalence.
CONCLUSIONS Considering different phenotype changes, different approaches should be conducted at the national level to reduce the burden and consequences of MetSyn between Korea and the United States.
PubMed IF 6.1 내분비대사내과
11422013

제1저자 박미영 · 교신저자 이춘택

, , , , , , , ,
Genetic blockade of insulin-like growth factor-1 receptor via recombinant adenovirus in lung cancer can be enhanced by the histone deacetylase inhibitor, vorinostat.
J Gene Med. 2013;15(3-4):115-22.

Abstract
BACKGROUND Many approaches have been suggested as anti-tumor therapy for targeting insulin-like growth factor 1 receptor (IGF-1R), such as monoclonal antibodies and tyrosine kinase inhibitor. We introduced recombinant adenoviruses expressing antisense, dominant negative or short hairpin RNA to IGF-1R. Moreover, we demonstrated that histone deacetylase inhibitor (vorinostat) can increase the transduction efficiency of adenoviruses by increasing CAR-induced transduction and by enhancing the transcription of the adenoviral transgene. In the present study, we showed that the combination of ad-sh (short hairpin) IGF-1R with vorinostat leads to a synergistic enhancement of IGF-1R blockade.
METHODS We measured the change in IGF-1R upon cotreatment with vorinostat and ad-shIGF-1R. Changes in transduction efficiency of ad-shIGF-1R were measured by fluorescent microscopy. Changes in apoptotic proportion and cell survival after the cotreatment were measured by the sub-G1 assay and cell counts. The effect of nuclear factor (NF)-κB activation was also measured by NF-κB p65 activation enzyme-linked immunosorbent assay. Drug interactions were analyzed upon cotreatment with ad-shIGF-1R, vorinostat and cisplatin.
RESULTS Combined treatment of ad-shIGF-1R and vorinostat synergistically suppressed the IGF-1R expression in lung cancer cell lines and also increased the transduction efficiency of ad-shIGF-1R. Ad-shIGF-1R and vorinostat cotreatment increased apoptotic cell death and synergistically suppressed cell growth compared to ad-shIGF-1R or vorinostat treatment alone. Vorinostat suppressed NF-κB activation, which was activated by ad-shIGF-1R. Moreover, triple combination of ad-shIGF-1R, vorinostat and cisplatin demonstrated synergistic cytotoxicity on lung cancer cells.
CONCLUSIONS Vorinostat enhanced the blocking capability of ad-shIGF-1R. The combined treatment of vorinostat and ad-sh-IGF-1R appears to have promising potential as a new therapeutic approach for lung cancer.
PubMed IF 3 호흡기내과
11412013

제1저자 Maruja Lira/김태민 · 교신저자 김동완/Mao Mao

, , , , , , , , , , , , , , , , ,
Multiplexed gene expression and fusion transcript analysis to detect ALK fusions in lung cancer.
J Mol Diagn. 2013;15(1):51-61.

Abstract
Anaplastic lymphoma kinase gene (ALK) fusions have been identified in approximately 5% of non-small-cell lung carcinomas (NSCLCs) and define a distinct subpopulation of patients with lung cancer who are highly responsive to ALK kinase inhibitors, such as crizotinib. Because of this profound therapeutic implication, the latest National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology recommend upfront ALK screening for all patients with NSCLC. The Food and Drug Administration-approved companion diagnostic test (ie, fluorescence in situ hybridization) for identification of ALK-positive patients, however, is complex and has considerable limitations in terms of cost and throughput, making it difficult to screen many patients. To explore alternative screening modalities for detecting ALK fusions, we designed a combination of two transcript-based assays to detect for presence or absence of ALK fusions using NanoString's nCounter technology. By using this combined gene expression and ALK fusion detection strategy, we developed a multiplexed assay with a quantitative scoring modality that is highly sensitive, reproducible, and capable of detecting low-abundant ALK fusion transcripts, even in samples with a low tumor cell content. In 66 archival NSCLC samples, our results were highly concordant to prior results obtained by fluorescence in situ hybridization and IHC. Our assay offers a cost-effective, easy-to-perform, high-throughput, and FFPE-compatible screening alternative for detection of ALK fusions.
PubMed IF 3.9 혈액종양내과
11402013

제1저자 음영욱, 김용태 · 교신저자 이상협

, , , , , , , , , , ,
Stent patency using competing risk model in unresectable pancreatic cancers inserted with biliary self-expandable metallic stent.
Dig Endosc. 2013;25(1):67-75.

Abstract
BACKGROUND AND AIM Biliary self-expandable metallic stents (SEMS) play an important role in the quality of life and palliative treatment in unresectable pancreatic cancer patients. We aimed to determine the factors affecting the patency of biliary SEMS and the survival in unresectable pancreatic cancer with obstructive jaundice.
METHODS Considering the competing risk and survival, we retrospectively evaluated the patency in 107 unresectable pancreatic cancer patients with obstructive jaundice who were successfully treated with biliary SEMS from January 2000 to April 2010.
RESULTS There were 107 incidents of biliary drainage that were clinically successful and the overall survival period was a median of 133 days. Stent occlusion before death was observed in 36 (33.6%) of 107 patients. Cumulative stent obstruction rates were 4.7%, 16.8%, and 24.4% at 1, 3, and 6 months, respectively. Lower cancer stage (<5 month's hazard ratio [HR] = 2.327, >5 month's HR = 0.108) was only associated with the longer patency of the stents in a multivariable analysis using a Fine and Gray model that considered competing risk. In multivariable analysis, lower cancer stage, uncovered stent and normalized serum bilirubin level were associated with a longer survival period (HR = 2.335, 1.906 and 1.795 respectively, P < 0.05).
CONCLUSION The patency of biliary SEMS in unresectable pancreatic cancers might be affected by the stage. Lower cancer stage and normalized bilirubin are associated with longer survival.
PubMed IF 3.6 소화기내과
11392013

제1저자 김지연 · 교신저자 김상균

, , , ,
Comparison of treatment outcomes of endoscopic stenting for colonic and extracolonic malignant obstruction.
Surg Endosc. 2013;27(1):272-7.

Abstract
BACKGROUND Self-expandable metal stents (SEMS) have been used as a bridging or palliative treatment for malignant colorectal obstruction. Colonic obstruction also may arise from advanced extracolonic malignancy, but the clinical outcomes of stent placement for extracolonic malignancy are unclear. This study compared the clinical outcomes of SEMS between patients with colorectal cancer and those with extracolonic malignancy.
METHODS Patients who underwent endoscopic SEMS placement for a malignant colorectal obstruction were enrolled at Seoul National University Hospital from April 2005 and August 2011. Their medical records were retrospectively reviewed in terms of success rate, complications, and duration of stent patency.
RESULTS Endoscopic SEMS placements were performed for colorectal cancer in 149 patients and for extracolonic malignancy in 60 patients. The causes of obstruction in extracolonic malignancy were advanced gastric cancer in 39 patients (65%), pancreatic cancer in nine patients (15%), ovarian cancer in three patients (5%) and other causes in nine patients (15%). The clinical success rates were similar between the two groups (92.6 vs 86.7%; p = 0.688), and multivariate analysis showed no significant risk factor for unsuccessful endoscopic SEMS placement. Reobstruction in palliative endoscopic SEMS placement occurred for 16 patients with colorectal cancer (21.9%) and 18 patients with extracolonic malignancy (30%) during a median follow-up period of 90 days (p = 0.288). The rates did not differ significantly between the two groups (4.1 vs 8.3%; p = 0.467). The median duration of stent patency was 193 ± 42 days for the patients with colorectal cancer and 186 ± 31 days for the patients with extracolonic malignancy (p = 0.253). The duration of stent patency was not affected by underlying malignancy, previous surgery, or palliative chemotherapy.
CONCLUSIONS Endoscopic SEMS placement is highly effective and comparable for palliation of obstruction in extracolonic malignancy and colorectal cancer in terms of clinical success, complications, and duration of patency.
PubMed IF 3.3 소화기내과

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