SCI 발표논문

1. 792012

   제1저자 정우경 · 교신저자 김세중

   Chung W, Jung ES, Shin D, Choi SH, Jung JY, Chang JH, Lee HH, Kim DK, Kim S

   Low resistin level is associated with poor hospitalization-free survival in hemodialysis patients.

   J Korean Med Sci. 2012;27(4):377-81.

   Abstract

   Malnutrition and inflammation are related to high rates of morbidity and mortality in hemodialysis patients. Resistin is associated with nutrition and inflammation. We attempted to determine whether resistin levels may predict clinical outcomes in hemodialysis patients. We conducted a prospective evaluation of 100 outpatients on hemodialysis in a single dialysis center (male, 46%; mean age, 53.7 ± 16.4 yr). We stratified the patients into 4 groups according to quartiles of serum resistin levels. During the 18-month observational period, patients with the lowest quartile of serum resistin levels had poor hospitalization-free survival (log rank test, P = 0.016). After adjustment of all co-variables, patients with the lowest quartile of serum resistin levels had poor hospitalization-free survival, compared with reference resistin levels. Higher levels of interleukin-6 were an independent predictor of poor hospitalization-free survival. In contrast, serum resistin levels were not correlated with interleukin-6 levels. The current data showed that low resistin levels may independently predict poor hospitalization free survival in hemodialysis patients.

   PubMed IF 3.2 신장내과
2. 782012

   제1저자 김진원 · 교신저자 임석아

   Kim JW, Im SA, Kim M, Cha Y, Lee KH, Keam B, Kim MA, Han SW, Oh DY, Kim TY, Kim WH, Bang YJ

   The prognostic significance of HER2 positivity for advanced gastric cancer patients undergoing first-line modified FOLFOX-6 regimen.

   Anticancer Res. 2012;32(4):1547-53.

   Abstract

   AIM We aimed to clarify the prognostic significance of HER2 positivity in advanced gastric cancer.

   PATIENTS AND METHODS The cohort included patients with initially metastatic or recurrent gastric cancer treated with first-line modified FOLFOX-6. The HER2 status was analyzed according to modified scoring criteria specific for gastric cancer.

   RESULTS HER2 positivity was shown in 10 out of 114 patients (9.0%). The median time-to-progression (TTP) (4.3 months, 95% confidence interval (CI)=3.6-4.9) and the overall survival (OS) (7.5 months, 95% CI=6.1-8.8) of patients with HER2-positive gastric cancer tended to be shorter than the median TTP (5.9 months, 95% CI=4.5-7.2) and OS (10.8 months, 95% CI=9.2-12.3) of those with HER2-negative gastric cancer (TTP, p=0.177; OS, p=0.068). Particularly in the subgroup of patients without diffuse-type histology, HER2-positive gastric cancer had a worse TTP than those with HER2-negative gastric cancer (p=0.024). In multivariate analysis of this subgroup, HER2 positivity and ECOG performance status of 2 were associated with shorter TTP (hazard ratio (HR)=2.926, p=0.014; HR=2.489, p=0.035, respectively).

   CONCLUSION HER2-positive gastric cancer seems to confer poorer prognosis, particularly in patients without diffuse-type tumor, treated with modified FOLFOX-6.

   PubMed IF 1.8 혈액종양내과
3. 772012

   제1저자 박은주 · 교신저자 방영주/오도연

   Park E, Park J, Han SW, Im SA, Kim TY, Oh DY, Bang YJ

   NVP-BKM120, a novel PI3K inhibitor, shows synergism with a STAT3 inhibitor in human gastric cancer cells harboring KRAS mutations.

   Int J Oncol. 2012;40(4):1259-66.

   Abstract

   Aberrations of Phosphoinositide 3-kinase (PI3K)/AKT signaling are frequently observed in many types of cancer, promoting its emergence as a promising target for cancer treatment. PI3K can become activated by various pathways, one of which includes RAS. RAS can not only directly activate the PI3K/AKT pathway via binding to p110 of PI3K, but also regulates mTOR via ERK or RSK independently of the PI3K/AKT pathway. Thus, actively mutated RAS can constitutively activate PI3K signaling. Additionally, in RAS tumorigenic transformation, signal transducer and activator of transcription 3 (STAT3) has been known also to be required. In this study, we examined the efficacy of NVP-BKM120, a pan-class I PI3K inhibitor in human gastric cancer cells and hypothesized that the combined inhibition of PI3K and STAT3 would be synergistic in KRAS mutant gastric cancer cells. NVP-BKM120 demonstrated anti-proliferative activity in 11 human gastric cancer cell lines by decreasing mTOR downstream signaling. But NVP-BKM120 treatment increased p-AKT by subsequent abrogation of feedback inhibition by stabilizing insulin receptor substrate-1. In KRAS mutant gastric cancer cells, either p-ERK or p-STAT3 was also increased upon treatment of NVP-BKM120. The synergistic efficacy study demonstrated that dual PI3K and STAT3 blockade showed a synergism in cells harboring mutated KRAS by inducing apoptosis. The synergistic effect was not seen in KRAS wild-type cells. Together, these findings suggest for the first time that the dual inhibition of PI3K and STAT3 signaling may be an effective therapeutic strategy for KRAS mutant gastric cancer patients.

   PubMed IF 7.3 혈액종양내과
4. 762012

   제1저자 전희중 · 교신저자 김동기

   Jeon HJ, Kim YS, Lee SM, Ahn C, Ha J, Kim SJ, Kim DK

   The effect of recurrent glomerulonephritis and acute rejection episodes in zero human leukocyte antigen-mismatched kidney transplantation.

   Transplant Proc. 2012;44(3):600-6.

   Abstract

   BACKGROUND Although human leukocyte antigen (HLA)-identical renal transplantation achieves superior graft outcomes, it does not uniformly allow indefinite graft survival. Recurrence of the original disease and effects of acute rejection episodes (ARE) may preclude indefinite survival. Herein, we have analyzed the factors that affect the graft outcomes among HLA zero-mismatch cases.

   METHODS We performed a retrospective, single-center study to evaluate the effect of recurrent glomerulonephritis (GN) and ARE on outcomes of grafts with zero HLA-mismatches (n = 122) versus three to four mismatches (n = 317), and five to six mismatches (n = 102). Forty-one percent of patients had GN as underlying disease.

   RESULTS Overall graft survival was 92.4% at 5 years and 79.6% at 10 years. HLA incompatibility did not affect graft survival: zero versus three to four versus five to six mismatches = 92.8% versus 90.8% versus 95.8% at 5 years and 82.5% versus 74.3% versus 85.1% at 10 years, respectively (P = .399). Subgroup analysis for subjects with GN revealed that ARE (P = .001) and recurrent GN (P = .003) were the risk factors for graft loss, whereas living donation was protective (P = .029). ARE was more prevalent with greater HLA incompatibility [0 (reference) < three to four < five to six mismatches; P = .047 and P = .014]. However, recurrent GN showed the opposite trend [0 (reference) > three to four > five to six mismatches; P = .106 and P = .022]. Furthermore, graft loss due to recurrent GN was significant among the HLA zero versus the three- to four-mismatch group (P = .047).

   CONCLUSIONS Graft survival was not affected by the degree of HLA incompatibility, which was mainly due to the recurrence of underlying disease. Therefore, a main focus should be the management of recurrence, especially among HLA-identical kidney transplantations.

   PubMed IF 0.8 신장내과
5. 752012

   제1저자 정재우 · 교신저자 강혜련

   Jung JW, Ju YS, Kang HR

   Association between parental smoking behavior and children's respiratory morbidity: 5-year study in an urban city of South Korea.

   Pediatr Pulmonol. 2012;47(4):338-45.

   Abstract

   INTRODUCTION After intensive tobacco control efforts in recent decades, the prevalence of active smoking has decreased. However, the hazardous effect of indirect exposure to cigarette smoke is often underestimated, especially in children. We aimed to investigate the effect of parental smoking on the respiratory morbidity of the children of parents who smoke by evaluating the relationship between parental smoking behavior and children's respiratory symptoms.

   METHODS We conducted a cross-sectional follow-up study of 31,584 children aged 6-11 in an urban community in Anyang City, Korea. The children's parents were asked about their smoking status and completed questionnaires regarding their children's symptoms related to asthma and other upper or lower respiratory illnesses. Our analysis focused on a comparison of the frequency of respiratory and ocular symptoms according to parental smoking status, whether it was non-smoking (Non-S), indirect passive smoking (third-hand smoking, THS) or direct passive smoking (second-hand smoking, SHS).

   RESULTS The children with Non-S patients were 40.9%, THS group 40.6%, and SHS group 18.5%. THS group showed lower ORs for most respiratory symptoms when compared with those of SHS group, however, THS group revealed increased ORs compared with Non-S in cough-related symptoms. There was a linear trend in frequencies of cough and sputum-related symptoms according to the degree of exposure to cigarette smoke (P < 0.05).

   CONCLUSION The prevalence of respiratory symptoms increased in children exposed to parental smoking including SHS and THS. To avoid the risk of respiratory and allergic disease by environmental tobacco smoke, absolute smoking cessation by parents is strongly recommended.

   PubMed IF 2.4 알레르기내과
6. 742012

   제1저자 김세훈 · 교신저자 조상헌

   Kim SH, Kim TW, Kwon JW, Kang HR, Lee YW, Kim TB, Kim SH, Park HW, Park SW, Chang YS, Cho YS, Park JW, Cho YJ, Yoon HJ, Cho SH, Choi BW, Moon HB, Min KU

   Economic costs for adult asthmatics according to severity and control status in Korean tertiary hospitals.

   J Asthma. 2012;49(3):303-9.

   Abstract

   OBJECTIVE The prevalence of asthma is increasing, and asthma causes considerable socioeconomic burden worldwide. Few studies have been conducted to evaluate the risk factors associated with economic cost of asthma in Korea. This study evaluated asthma cost according to severity, control, and patient factors in Korean tertiary hospitals.

   METHODS Direct and indirect costs were assessed in physician-diagnosed adult asthmatics recruited from eight tertiary hospitals in Korea. Official direct medical costs were derived from the analysis of 1-year expenditures related to hospital care utilization and asthma medication. Nonofficial medical costs, nonmedical direct costs, and indirect costs were investigated using a questionnaire designed specifically for the study.

   RESULTS A total of 314 patients with persistent asthma were recruited. Both direct and indirect costs were significantly higher for patients with severe persistent asthma than for those with mild and moderate persistent asthma ($2214 vs. $871 and $978, p < .001; $2927 vs. $490 and $443, p < .001, respectively). Costs of asthma increased significantly in poorly controlled compared with somewhat controlled and well-controlled asthma ($7009.8 vs. $2725.3 vs. $1517.3, respectively; p < .001). After stratification for severity, a significant cost increase in the poorly controlled asthma group was observed only for indirect costs and not for direct costs. A multivariate analysis showed that female gender was a risk factor for increased indirect costs.

   CONCLUSION The burden of asthma was higher both for patients with severe persistent asthma and for patients with poorly controlled asthma. More effective strategies are needed to improve control status, particularly targeting patients with severe asthma.

   PubMed IF 1.6 알레르기내과
7. 732012

   제1저자 고진신 · 교신저자 구본권

   Koh JS, Koo BK, Kim JH, Yang HM, Park KW, Kang HJ, Kim HS, Oh BH, Park YB

   Relationship between fractional flow reserve and angiographic and intravascular ultrasound parameters in ostial lesions: major epicardial vessel versus side branch ostial lesions.

   JACC Cardiovasc Interv. 2012;5(4):409-15.

   Abstract

   OBJECTIVES This study sought to assess the relationship of coronary angiography, intravascular ultrasound (IVUS) and fractional flow reserve (FFR) between major epicardial vessel (MV) and side branch (SB) ostial lesions.

   BACKGROUND Evaluation of ostial lesions is clinically very important. However, anatomical parameters have limitations in the prediction of the functional significance of coronary stenoses.

   METHODS IVUS and FFR measurement were performed in 93 lesions (MV: 38, SB: 55). Optimal angiographic and IVUS criteria and their diagnostic accuracy for functionally significant stenoses (FFR ≤0.8) were assessed.

   RESULTS In MV ostial lesions, FFR had correlation with angiographic percent diameter stenosis (r = -0.68, p < 0.001), minimum lumen area (MLA) by IVUS (r = 0.55, p < 0.001), percent plaque burden (r = -0.42, p = 0.011), and percent area stenosis (r = -0.49, p = 0.003). Meanwhile, FFR had no correlation with angiographic percent diameter stenosis (r = -0.067, p = 0.635) and weak correlation with MLA (r = 0.30, p = 0.026) in SB ostial lesions. In MV ostial lesions, best cutoff value of angiographic percent diameter stenosis, MLA, percent plaque burden, and percent area stenosis to determine the functional significance was 53%, 3.5 mm(2), 70%, and 50%. However, a statistically significant cutoff value of percent diameter stenosis and MLA could not be found in SB ostial lesions.

   CONCLUSIONS The relations between angiographic/IVUS parameters and FFR were different between MV and SB ostial lesions. Angiographic and IVUS parameters had poor diagnostic accuracy in predicting the functional significance of SB ostial lesions. (Main Branch Versus Side Branch Ostial Lesion; NCT01335659).

   PubMed IF 12.7 순환기내과
8. 722012

   제1저자 박경일 · 교신저자 김효수

   Park K, Park KW, Rha SW, Bae JH, Hur SH, Park JS, Yoon JH, Jang Y, Jeong MH, Kim HS

   Comparison of 5-year clinical outcomes between sirolimus-versus paclitaxel-eluting stent: Korean multicenter network analysis of 9000-patient cohort.

   Circ Cardiovasc Interv. 2012;5(2):174-84.

   Abstract

   BACKGROUND The paclitaxel-eluting stent (PES) and sirolimus-eluting stent (SES) are first-generation drug-eluting stents (DES) that have been the most widely used; however, it is unclear whether there are differences in the long-term safety and efficacy between the 2 stents. The long-term effectiveness of DES in unselected people with diabetes is also currently unclear. Moreover, the possibility of late catch-up is suggested in the DES population.

   METHODS AND RESULTS This study is an 8-center collaborative network analysis of all comers who received SES and PES. All patients who received SES and PES from February 2003 to October 2006 were enrolled. We analyzed 9315 patients (33.3% with diabetes) treated with SES or PES in the major 8 centers representing whole area of Korea. The primary end point was a major adverse cardiac event (MACE) composite of overall death, myocardial infarction, and target lesion revascularization. All analyses were performed using multivariable, adjusted models and propensity score-matching methods. Long-term MACE for 5 years were significantly lower in the SES than the PES group (13.3% versus 15.6%; hazard ratio, 0.82; 95% confidence interval, 0.71 to 0.96; P=0.01), which was mainly driven by the difference of MACE within the first year (hazard ratio, 0.73; 95% CI, 0.59 to 0.90; P=0.003), but the rate of MACE between 1 and 5 years in the landmark analysis was not different between the 2 stents (1.9 versus 2.0%/yr). In the subpopulation of people with diabetes, in contrast to the whole population, PES was comparable to SES in terms of any clinical outcome, both within the first year and from 1 to 5 years (MACE for 5 years, 20.3 versus 17.9%; MACE within the first year, 9.6 versus 8.2%; MACE 1 to 5 years, 2.9 versus 2.6%/yr).

   CONCLUSIONS The PES was inferior to the SES in the clinical follow-up of more than 9000 patients' cohort for 5 years, which was mainly driven by the difference in the first year. In the subpopulation of people with diabetes that showed higher MACE than people without diabetes, however, PES was comparable to SES in any clinical outcome for 5 years. Although these 2 stents are not frequently used as before, the data would be useful to expect the long-term clinical course of the current DES.

   PubMed IF 7.2 순환기내과
9. 712012

   제1저자 김동기 · 교신저자 강신욱

   Kim DK, Nam BY, Li JJ, Park JT, Lee SH, Kim DH, Kim JY, Kang HY, Han SH, Yoo TH, Han DS, Kang SW

   Translationally controlled tumour protein is associated with podocyte hypertrophy in a mouse model of type 1 diabetes.

   Diabetologia. 2012;55(4):1205-17.

   Abstract

   AIMS/HYPOTHESIS Translationally controlled tumour protein (TCTP) is thought to be involved in cell growth by regulating mTOR complex 1 (mTORC1) signalling. As diabetes characteristically induces podocyte hypertrophy and mTORC1 has been implicated in this process, TCTP may have a role in the pathogenesis of diabetes-induced podocyte hypertrophy.

   METHODS We investigated the effects and molecular mechanisms of TCTP in diabetic mice and in high glucose-stimulated cultured podocytes. To characterise the role of TCTP, we conducted lentivirus-mediated gene silencing of TCTP both in vivo and in vitro.

   RESULTS Glomerular production of TCTP was significantly higher in streptozotocin induced-diabetic DBA/2J mice than in control animals. Double-immunofluorescence staining for TCTP and synaptopodin revealed that podocyte was the principal cell responsible for this increase. TCTP knockdown attenuated the activation of mTORC1 downstream effectors and the overproduction of cyclin-dependent kinase inhibitors (CKIs) in diabetic glomeruli, along with a reduction in proteinuria and a decrease in the sizes of podocytes as well as glomeruli. In addition, knockdown of TCTP in db/db mice prevented the development of diabetic nephropathy, as indicated by the amelioration of proteinuria, mesangial expansion, podocytopenia and glomerulosclerosis. In accordance with the in vivo data, TCTP inhibition abrogated high glucose-induced hypertrophy in cultured podocytes, which was accompanied by the downregulation of mTORC1 effectors and CKIs.

   CONCLUSIONS/INTERPRETATION These findings suggest that TCTP might play an important role in the process of podocyte hypertrophy under diabetic conditions via the regulation of mTORC1 activity and the induction of cell-cycle arrest.

   PubMed IF 10.4 신장내과
10. 702012

    제1저자 김충종 · 교신저자 김남중

    Kim CJ, Song KH, Park WB, Kim ES, Park SW, Kim HB, Oh MD, Kim NJ

    Microbiologically and clinically diagnosed vertebral osteomyelitis: impact of prior antibiotic exposure.

    Antimicrob Agents Chemother. 2012;56(4):2122-4.

    Abstract

    We retrospectively reviewed medical records to identify the factors that affect the results of culture in patients with pyogenic vertebral osteomyelitis. In multivariate analysis, the presence of paravertebral abscess was associated with positive results of microbiologic culture. Prior antibiotic exposure, especially of longer duration, was strongly associated with negative results.

    PubMed IF 4.2 감염내과
11. 692012

    제1저자 강신애 · 교신저자 박경수

    Kang S, Park HS, Jo A, Hong SH, Lee HN, Lee YY, Park JS, Jung HS, Chung SS, Park KS

    Endothelial progenitor cell cotransplantation enhances islet engraftment by rapid revascularization.

    Diabetes. 2012;61(4):866-76.

    Abstract

    Impaired revascularization of transplanted islets is a critical problem that leads to progressive islet loss. Since endothelial progenitor cells (EPCs) are known to aid neovascularization, we aimed to enhance islet engraftment by cotransplanting EPCs with islets. Porcine islets, with (islet-EPC group) or without (islet-only group) human cord blood-derived EPCs, were transplanted into diabetic nude mice. The islet-EPC group reached euglycemia by ∼11 days posttransplantation, whereas the islet-only group did not. Also, the islet-EPC group had a higher serum porcine insulin level than the islet-only group. Islets from the islet-EPC group were more rapidly revascularized at the early period of transplantation without increment of final capillary density at the fully revascularized graft. Enhanced revascularization rate in the islet-EPC group was mainly attributed to stimulating vascular endothelial growth factor-A production from the graft. The rapid revascularization by EPC cotransplantation led to better graft perfusion and recovery from hypoxia. EPC cotransplantation was also associated with greater β-cell proliferation, probably by more basement membrane production and hepatocyte growth factor secretion. In conclusion, cotransplantation of EPCs and islets induces better islet engraftment by enhancing the rate of graft revascularization. These findings might provide a directly applicable tool to enhance the efficacy of islet transplantation in clinical practice.

    PubMed IF 9.3 내분비대사내과
12. 682012

    제1저자 임주현, 김상균 · 교신저자 김지원

    Lim JH, Kim SG, Kim JW, Choi YJ, Kwon J, Kim JY, Lee YB, Choi J, Im JP, Kim JS, Jung HC, Song IS

    Do antiplatelets increase the risk of bleeding after endoscopic submucosal dissection of gastric neoplasms?

    Gastrointest Endosc. 2012;75(4):719-27.

    Abstract

    BACKGROUND It is rarely known whether antiplatelets increase the risk of bleeding after endoscopic submucosal dissection (ESD).

    OBJECTIVE To evaluate the effect of antiplatelets on post-ESD bleeding.

    DESIGN Retrospective study.

    SETTING Single, tertiary-care referral center.

    PATIENTS This study involved 1591 gastric neoplasms (815 adenomas and 776 early gastric cancers) in 1503 patients who had ESD between April 2005 and April 2010.

    INTERVENTION ESD.

    MAIN OUTCOME MEASUREMENTS Overt hematemesis/hematochezia, a drop of hemoglobin >2 g/dL from baseline, or requirement of endoscopic hemostasis, angiographic embolization, and/or transfusion.

    RESULTS Of 1591 subjects, 274 took antiplatelets, among whom 102 discontinued them for 7 days or more before ESD. Post-ESD bleeding occurred in 94 subjects including 20 from the continuation group, 6 from the withdrawal group, and 68 from the no-antiplatelet group. In univariate analysis, antiplatelets, early gastric cancer (EGC), comorbidity, and specimen diameter were related to post-ESD bleeding. In multivariate analysis, EGC (odds ratio [OR] 1.839; 95% confidence interval [CI], 1.168-2.896; P = .009), comorbidity (OR 2.246; 95% CI, 1.280-3.939; P = .005), and specimen diameter (OR 2.315; 95% CI, 1.282-4.180; P = .005) were independent risk factors of post-ESD bleeding, whereas antiplatelet usage was not (OR 1.596; 95% CI, 0.877-2.903; P = .126). In subgroup analysis, continuous antiplatelet usage was not found to be an independent risk factor of post-ESD bleeding in multivariate analysis (OR 2.027; P = .146). Among 102 subjects who discontinued antiplatelets, 1 developed an acute cerebral infarction (1.0%).

    LIMITATION A retrospective, single-center analysis.

    CONCLUSION In ESD for antiplatelet users, continuous administration was not found to have an independent significant association with bleeding.

    PubMed IF 8 소화기내과
13. 672012

    제1저자 박경우 · 교신저자 김효수

    Park KW, Park BE, Kang SH, Park JJ, Lee SP, Cha KS, Rhew JY, Jeon HK, Shin ES, Oh JH, Jeong MH, Kim S, Hwang KK, Yoon JH, Lee SY, Park TH, Moon KW, Kwon HM, Chae IH, Kim HS, HOST investigators

    The 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial: study protocol for a randomized controlled trial.

    Trials. 2012;13:29.

    Abstract

    BACKGROUND Second-generation drug-eluting stents (DES) have raised the bar of clinical performance. These stents are mostly made from cobalt chromium alloy. A newer generation DES has been developed from platinum chromium alloy, but clinical data regarding the efficacy and safety of the platinum chromium-based everolimus-eluting stent (PtCr-EES) is limited, with no comparison data against the cobalt chromium-based zotarolimus-eluting stent (CoCr-ZES). In addition, an antiplatelet regimen is an integral component of medical therapy after percutaneous coronary intervention (PCI). A 1-week duration of doubling the dose of clopidogrel (double-dose antiplatelet therapy (DDAT)) was shown to improve outcome at 1 month compared with conventional dose in acute coronary syndrome (ACS) patients undergoing PCI. However in Asia, including Korea, the addition of cilostazol (triplet antiplatelet therapy (TAT)) is used more commonly than doubling the dose of clopidogrel in high-risk patients.

    METHODS In the 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial, approximately 3,750 patients are being prospectively and randomly assigned in a 2 × 2 factorial design according to the type of stent (PtCr-EES vs CoCr-ZES) and antiplatelet regimen (TAT vs DDAT). The first primary endpoint is target lesion failure at 1 year for the stent comparison, and the second primary endpoint is net clinical outcome at 1 month for comparison of antiplatelet therapy regimen.

    DISCUSSION The HOST-ASSURE trial is the largest study yet performed to directly compare the efficacy and safety of the PtCr-EES versus CoCr-ZES in an 'all-comers' population. In addition, this study will also compare the clinical outcome of TAT versus DDAT for 1-month post PCI.

    TRIAL REGISTRATION ClincalTrials.gov number NCT01267734.

    PubMed IF 2.1 순환기내과
14. 662012

    제1저자 진종화 · 교신저자 박경수/김영수

    Jin J, Ku YH, Kim Y, Kim Y, Kim K, Lee JY, Cho YM, Lee HK, Park KS, Kim Y

    Differential proteome profiling using iTRAQ in microalbuminuric and normoalbuminuric type 2 diabetic patients.

    Exp Diabetes Res. 2012;2012:168602.

    Abstract

    Diabetic nephropathy (DN) is a long-term complication of diabetes mellitus that leads to end-stage renal disease. Microalbuminuria is used for the early detection of diabetic renal damage, but such levels do not reflect the state of incipient DN precisely in type 2 diabetic patients because microalbuminuria develops in other diseases, necessitating more accurate biomarkers that detect incipient DN. Isobaric tags for relative and absolute quantification (iTRAQ) were used to identify urinary proteins that were differentially excreted in normoalbuminuric and microalbuminuric patients with type 2 diabetes where 710 and 196 proteins were identified and quantified, respectively. Some candidates were confirmed by 2-DE analysis, or validated by Western blot and multiple reaction monitoring (MRM). Specifically, some differentially expressed proteins were verified by MRM in urine from normoalbuminuric and microalbuminuric patients with type 2 diabetes, wherein alpha-1-antitrypsin, alpha-1-acid glycoprotein 1, and prostate stem cell antigen had excellent AUC values (0.849, 0.873, and 0.825, resp.). Moreover, we performed a multiplex assay using these biomarker candidates, resulting in a merged AUC value of 0.921. Although the differentially expressed proteins in this iTRAQ study require further validation in larger and categorized sample groups, they constitute baseline data on preliminary biomarker candidates that can be used to discover novel biomarkers for incipient DN.

    PubMed IF 1.528 내분비대사내과
15. 652012

    제1저자 강현재 · 교신저자 김효수

    Kang HJ, Yoon EJ, Lee EJ, Kim MK, Suh JW, Park KW, Lee HY, Park KU, Cho YS, Koo BK, Chae IH, Choi DJ, Han KS, Kim HS, Park YB

    Cotreatment with darbepoetin and granulocyte colony-stimulating factor is efficient to recruit proangiogenic cell populations in patients with acute myocardial infarction.

    Cell Transplant. 2012;21(5):1055-61.

    Abstract

    UNLABELLED To determine whether newer combination cytokine treatment with granulocyte colony-stimulating factor (G-CSF) and darbepoetin can improve efficacy of stem cell therapy, we evaluated safety and peripheral blood stem/progenitor cell (PBSC) mobilizing effects of combination cytokine in comparison with G-CSF alone in patients with acute myocardial infarction (AMI). We randomized 60 patients with AMI into two groups under 2:1 ratio; combination treatment with darbepoetin and G-CSF (n = 41: Combicytokine group) and the G-CSF alone (n = 19: G-CSF group). After coronary angioplasty, G-CSF was treated for 3 days with dose of 10 μg/kg/day in both groups. Only in the combicytokine group, additional single intravenous injection of 4.5 μg/kg of darbepoetin was administrated immediate after coronary angioplasty. Combination cytokine treatment was well tolerated as was G-CSF alone. PBSCs were obtained by apheresis for intracoronary infusion after completion of cytokine treatment and were analyzed by flow cytometry. The purity of proangiogenic cells was higher in combination cytokine group than the G-CSF group. Specifically, proportion of CD34(+)/KDR(+) endothelial progenitor cells, CD3(+)/CD31(+) angiogenic T cells and Tie2(+)/CXCR4(+) cells in apheresis products were higher in the combicytokine group. These meant that the combicytokine treatment recruited PBSCs in higher purity and fewer unwanted inflammatory cells than G-CSF alone in apheresis products. Combination treatment with darbepoetin and G-CSF is safe and more efficient to mobilize and recruit proangiogenic cells than G-CSF alone in patients with AMI. (

    TRIAL REGISTRATION www.ClinicalTrials. gov identifier: NCT00501917).

    PubMed IF 3.7 순환기내과
16. 642012

    제1저자 최의근 · 교신저자 Peng-Sheng Chen

    Choi EK, Chang PC, Lee YS, Lin SF, Zhu W, Maruyama M, Fishbein MC, Chen Z, Rubart-von der Lohe M, Field LJ, Chen PS

    Triggered firing and atrial fibrillation in transgenic mice with selective atrial fibrosis induced by overexpression of TGF-β1.

    Circ J. 2012;76(6):1354-62.

    Abstract

    BACKGROUND Calcium transient triggered firing (CTTF) is induced by large intracellular calcium (Ca(i)) transient and short action potential duration (APD). We hypothesized that CTTF underlies the mechanisms of early afterdepolarization (EAD) and spontaneous recurrent atrial fibrillation (AF) in transgenic (Tx) mice with overexpression of transforming growth factor β1 (TGF-β1).

    METHODS AND RESULTS MHC-TGFcys(33)ser Tx mice develop atrial fibrosis because of elevated levels of TGF-β1. We studied membrane potential and Ca(i)transients of isolated superfused atria from Tx and wild-type (Wt) littermates. Short APD and persistently elevated Ca(i) transients promoted spontaneous repetitive EADs, triggered activity and spontaneous AF after cessation of burst pacing in Tx but not Wt atria (39% vs. 0%, P=0.008). We were able to map optically 4 episodes of spontaneous AF re-initiation. All first and second beats of spontaneous AF originated from the right atrium (4/4, 100%), which is more severely fibrotic than the left atrium. Ryanodine and thapsigargin inhibited spontaneous re-initiation of AF in all 7 Tx atria tested. Western blotting showed no significant changes of calsequestrin or sarco/endoplasmic reticulum Ca(2+)-ATPase 2a.

    CONCLUSIONS Spontaneous AF may occur in the Tx atrium because of CTTF, characterized by APD shortening, prolonged Ca(i) transient, EAD and triggered activity. Inhibition of Ca(2+) release from the sarcoplasmic reticulum suppressed spontaneous AF. Our results indicate that CTTF is an important arrhythmogenic mechanism in TGF-β1 Tx atria.

    PubMed IF 5.8 순환기내과
17. 632012

    제1저자 김경희 · 교신저자 김용진

    Kim KH, Kim YJ, Ohn JH, Yang J, Lee SE, Lee SW, Kim HK, Seo JW, Sohn DW

    Long-term effects of sildenafil in a rat model of chronic mitral regurgitation: benefits of ventricular remodeling and exercise capacity.

    Circulation. 2012;125(11):1390-401.

    Abstract

    BACKGROUND We tested the hypothesis that chronic treatment with sildenafil attenuates left ventricular (LV) remodeling and prevents exercise intolerance in chronic mitral regurgitation (MR).

    METHODS AND RESULTS MR was created in Sprague-Dawley rats by making a hole on the mitral leaflet. Two weeks after MR creation, MR and LV dilatation were confirmed by echocardiography, and rats were randomly assigned to sildenafil treatment (MR+sildenafil group; 50 mg/kg PO twice a day; n=16) or normal saline only (MR group; n=16) and continued for 4 months. Sixteen sham rats were compared with MR rats. After 4 months, LV size was smaller in the MR+sildenafil compared with the MR group (LV end-systolic dimension, 4.7±0.3 for sham versus 5.9±0.3 for MR+sildenafil versus 7.4±0.5 mm for MR; P<0.05; LV end-diastolic dimension, 8.3±0.4 versus 10.5±0.2 versus 11.7±0.61 mm, respectively; P<0.05). LV ejection fraction was greater in the MR+sildenafil group than in the MR group (70.2±2.2 for sham versus 67.0±4.2 for MR+sildenafil versus 58.9±2.5 for MR; P=0.01). Serial treadmill test revealed that exercise capacity was reduced in the MR but not in the MR+sildenafil group. Transcriptional profiling of cardiac apical tissues revealed that gene sets related to inflammatory response, DNA damage response, cell cycle checkpoint, and cellular signaling pathways were significantly enriched by genes with reciprocal changes. Pathological analysis showed that perivascular fibrosis was more prominent in the MR than in the MR+sildenafil group and that the percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells was 2-fold greater in the MR compared with the MR+sildenafil group.

    CONCLUSIONS Sildenafil significantly attenuates LV remodeling and prevents exercise intolerance in a rat model of chronic MR. This benefit may be associated with the antiapoptotic, anti-inflammatory effects of sildenafil.

    PubMed IF 41.3 순환기내과
18. 622012

    제1저자 김준규 · 교신저자 김태유

    Kim JG, Kang MJ, Yoon YK, Kim HP, Park J, Song SH, Han SW, Park JW, Kang GH, Kang KW, Oh DY, Im SA, Bang YJ, Yi EC, Kim TY

    Heterodimerization of glycosylated insulin-like growth factor-1 receptors and insulin receptors in cancer cells sensitive to anti-IGF1R antibody.

    PLoS One. 2012;7(3):e33322.

    Abstract

    BACKGROUND Identification of predictive biomarkers is essential for the successful development of targeted therapy. Insulin-like growth factor 1 receptor (IGF1R) has been examined as a potential therapeutic target for various cancers. However, recent clinical trials showed that anti-IGF1R antibody and chemotherapy are not effective for treating lung cancer.

    METHODOLOGY/PRINCIPAL FINDINGS In order to define biomarkers for predicting successful IGF1R targeted therapy, we evaluated the anti-proliferation effect of figitumumab (CP-751,871), a humanized anti-IGF1R antibody, against nine gastric and eight hepatocellular cancer cell lines. Out of 17 cancer cell lines, figitumumab effectively inhibited the growth of three cell lines (SNU719, HepG2, and SNU368), decreased p-AKT and p-STAT3 levels, and induced G 1 arrest in a dose-dependent manner. Interestingly, these cells showed co-overexpression and altered mobility of the IGF1R and insulin receptor (IR). Immunoprecipitaion (IP) assays and ELISA confirmed the presence of IGF1R/IR heterodimeric receptors in figitumumab-sensitive cells. Treatment with figitumumab led to the dissociation of IGF1-dependent heterodimeric receptors and inhibited tumor growth with decreased levels of heterodimeric receptors in a mouse xenograft model. We next found that both IGF1R and IR were N-linked glyosylated in figitumumab-sensitive cells. In particular, mass spectrometry showed that IGF1R had N-linked glycans at N913 in three figitumumab-sensitive cell lines. We observed that an absence of N-linked glycosylation at N913 led to a lack of membranous localization of IGF1R and figitumumab insensitivity.

    CONCLUSION AND SIGNIFICANCE The data suggest that the level of N-linked glycosylated IGF1R/IR heterodimeric receptor is highly associated with sensitivity to anti-IGF1R antibody in cancer cells.

    PubMed IF 2.8 혈액종양내과
19. 612012

    제1저자 강시혁 · 교신저자 최동주

    Kang SH, Suh JW, Yoon CH, Cho MC, Kim YJ, Chae SC, Yoon JH, Gwon HC, Han KR, Kim JH, Ahn YK, Jeong MH, Kim HS, Choi DJ, KAMIR/KorMI Registry

    Sex differences in management and mortality of patients with ST-elevation myocardial infarction (from the Korean Acute Myocardial Infarction National Registry).

    Am J Cardiol. 2012;109(6):787-93.

    Abstract

    There has been controversy over the disparity between men and women with regard to the management and prognosis of acute myocardial infarction. Analyzing nationwide multicenter prospective registries in Korea, the aim of this study was to determine whether female gender independently imposes a risk for mortality. Data from 14,253 patients who were hospitalized for ST-segment elevation myocardial infarction from November 2005 to September 2010 were extracted from registries. Compared to men, women were older (mean age 56 ± 12 vs 67 ± 10 years, p < 0.001), and female gender was associated with a higher frequency of co-morbidities, including hypertension, diabetes, and dyslipidemia. Women had longer pain-to-door time and more severe hemodynamic status than men. All-cause mortality rates were 13.6% in women and 7.0% in men at 1 year after the index admission (hazard ratio for women 2.01, 95% confidence interval 1.80 to 2.25, p < 0.001). The risk for death after ST-segment elevation myocardial infarction corresponded highly with age. Although the risk remained high after adjusting for age, further analyses adjusting for medical history, clinical performance, and hemodynamic status diminished the gender effect (hazard ratio 1.00, 95% confidence interval 0.86 to 1.17, p = 0.821). Propensity score matching, as a sensitivity analysis, corroborated the results. In conclusion, this study shows that women have a comparable risk for death after ST-segment elevation myocardial infarction as men. The gender effect was accounted for mostly by the women's older age, complex co-morbidities, and severe hemodynamic conditions at presentation.

    PubMed IF 2.5 순환기내과
20. 602012

    제1저자 강효재 · 교신저자 임재준

    Kang HJ, Park JS, Kim DW, Lee J, Jeong YJ, Choi SM, Lee SM, Yang SC, Yoo CG, Kim YW, Han SK, Yim JJ

    Adverse pulmonary reactions associated with the use of monoclonal antibodies in cancer patients.

    Respir Med. 2012;106(3):443-50.

    Abstract

    BACKGROUND The incidence and clinical characteristics of adverse pulmonary reactions resulting from anticancer monoclonal antibody (mAbs) therapy have not been well described. We determined the incidence and clinical characteristics of adverse pulmonary reactions in patients treated with anticancer chemotherapy including mAbs.

    METHODS A retrospective cohort study was performed including patients who were treated with a chemotherapeutic regimen that included rituximab, trastuzumab, cetuximab, or bevacizumab at Seoul National University Hospital between January 1, 2004 and December 31, 2008. Rates of adverse pulmonary reactions classified as non-infectious and infectious complications were compared with those among patients treated with comparable regimens without mAbs.

    RESULTS In total, 1078 patients were included (418 for rituximab, 329 for trastuzumab, 122 for cetuximab, 209 for bevacizumab). Adverse pulmonary reactions were identified in 36 patients (3.5%) and the incidence differed among agents: cetuximab (9%), rituximab (5.3%), trastuzumab (0.6%), bevacizumab (0.5%). Infectious pulmonary complications occurred in 28 patients, and eight patients experienced non-infectious pulmonary complications, most commonly interstitial lung disease (6 patients). In a multivariate analysis, low serum albumin level was associated with the development of pulmonary complications. The incidence of overall adverse pulmonary reactions did not differ between the mAbs users and the 1012 patients treated with comparable regimens other than mAbs (3.5% vs. 2.8%, P=0.53).

    CONCLUSIONS Infectious and non-infectious adverse pulmonary reactions occur in patients with cancer who are administered a regimen including mAbs. Clinicians should be alert for the possibility of pulmonary adverse reactions, particularly among patients with low serum albumin levels.

    PubMed IF 3.3 호흡기내과
21. 592012

    제1저자 김민혜 · 교신저자 장윤석

    Kim MH, Park CH, Kim DI, Kim KM, Kim HK, Lim KH, Song WJ, Lee SM, Kim SH, Kwon HS, Park HW, Yoon CJ, Cho SH, Min KU, Kim YY, Chang YS

    Surveillance of contrast-media-induced hypersensitivity reactions using signals from an electronic medical recording system.

    Ann Allergy Asthma Immunol. 2012;108(3):167-71.

    Abstract

    BACKGROUND Contrast-media (CM) hypersensitivity is a well-known adverse drug reaction. Surveillance of adverse drug reactions usually depends on spontaneous reports. However, the rate of spontaneous reports is low. Recent progress in information technology enables the electronic search on signals of adverse drug reactions from electronic medical recording (EMR) systems.

    OBJECTIVES To analyze the incidence and clinical characteristics of CM hypersensitivity using an EMR-based surveillance system.

    METHODS The surveillance system used signals from standardized terms within the international classification of nursing practice terms that can indicate symptoms of CM hypersensitivity and from the order codes for procedures that used contrast media, antihistamine, and epinephrine. The search strategy was validated by allergists comparing the electronic search strategy versus manually reviewing medical charts over one month. The main study covered for one year period.

    RESULTS Detection rate of the electronic search method was 0.9% (7/759), while that of the manual search method was 0.8% (6/759). EMR-based electronic search method was highly efficient: reduced the charts that needed to be reviewed by 96% (28/759). The sensitivity of electronic screening was 66.7%, specificity was 99.6%, and the negative predictive value was 99.7%. CM hypersensitivity reactions were noted in 266 among 12,483 cases (2.1%). Urticaria was the most frequent symptom (74.4%). CT was the most frequent procedure (3.6%) that induced CM hypersensitivity.

    CONCLUSION A surveillance system using EMR may be a useful tool in the study of drug hypersensitivity epidemiology and may be used in an adverse drug reaction alarm system and as a clinical, decision making support system.

    PubMed IF 7.1 알레르기내과
22. 582012

    제1저자 김의석 · 교신저자 김백남

    Kim ES, Park SW, Lee CS, Gyung Kwak Y, Moon C, Kim BN

    Impact of a national hospital evaluation program using clinical performance indicators on the use of surgical antibiotic prophylaxis in Korea.

    Int J Infect Dis. 2012;16(3):e187-92.

    Abstract

    OBJECTIVES Clinical performance measurement in surgical antibiotic prophylaxis (SAP) was implemented as part of a national hospital evaluation program (NHEP) in Korea in 2007. This study investigated changes in SAP quality before and after the implementation of clinical performance measurement.

    METHODS The medical records of patients who underwent three types of surgery that were included for assessment in the NHEP (NHEP surgery) - arthroplasty, gastrectomy, and hysterectomy - and two other types of non-NHEP assessment surgery - craniotomy and spine surgery (non-NHEP surgery) - at six hospitals, from August to October in 2006-2008, were retrospectively reviewed. Three clinical indicators of SAP (antibiotic selection, timing of administration of the first dose, and duration) and the development of surgical site infections (SSIs) were compared before and after implementation.

    RESULTS A total of 1949 patients were enrolled: 356 arthroplasty, 273 gastrectomy, 615 hysterectomy, 168 craniotomy, and 537 spinal surgery. There were no significant changes in age, gender, wound class, or ASA score for each surgery during the study period. From 2007, SAP quality was significantly improved in NHEP surgery for the three clinical indicators. The timing of administration of the first dose was most markedly improved. SAP quality was also improved in non-NHEP surgery, but not as much as in NHEP surgery. Changes in the SSI rates for each surgery were not significant.

    CONCLUSIONS Hospital evaluation using clinical performance indicators can considerably improve the use of SAP. Further studies are warranted to investigate whether this hospital evaluation will decrease the development of SSIs.

    PubMed IF 4.6 감염내과
23. 572012

    제1저자 윤창환 · 교신저자 최동주

    Yoon CH, Youn TJ, Ahn S, Choi DJ, Cho GY, Chae IH, Choi J, Cho H, Han S, Cho MC, Jeon ES, Chae SC, Kim JJ, Ryu KH, Oh BH, Korean Heart Failure Registry

    Low serum total cholesterol level is a surrogate marker, but not a risk factor, for poor outcome in patients hospitalized with acute heart failure: a report from the Korean Heart Failure Registry.

    J Card Fail. 2012;18(3):194-201.

    Abstract

    BACKGROUND Hypercholesterolemia is a major risk factor for incident coronary artery disease and the prevalence of heart failure (HF). The causal relationship between low total cholesterol (TC) levels and poor clinical outcome in patients with acute HF has not been investigated. This study evaluated the effect of cholesterol levels on the long-term outcome in patients hospitalized due to acute HF.

    METHODS AND RESULTS We analyzed a cohort of 2,797 HF patients who were eligible for analysis in 3,200 patients of the Korean Heart Failure Registry. Patients were stratified into quartiles of TC (Q1 <133, Q2 133-158, Q3 159-190, and Q4 >190 mg/dL). Propensity score matching was performed with the patients in Q1 and Q4. Patients with lower serum TC had lower blood pressure, lower hemoglobin, lower serum sodium, and higher natriuretic peptide levels than patients with higher TC levels. Low TC was associated with increased risks for death and readmission due to HF; the adjusted hazard ratio (HR) of Q1 compared with Q4 was 1.57 (95% confidence interval [CI] 1.30-1.90). However, propensity score matching analysis revealed that low cholesterol itself did not affect outcome (HR 1.12, 95% CI 0.85-1.48).

    CONCLUSIONS Low TC is strongly associated with mortality and morbidity in patients with HF. However, low TC seemed to be a secondary result of the patient's state rather than an independent risk factor for poor outcome.

    PubMed IF 9.9 순환기내과
24. 562012

    제1저자 정성수 · 교신저자 박경수

    Chung SS, Lee JS, Kim M, Ahn BY, Jung HS, Lee HM, Kim JW, Park KS

    Regulation of Wnt/β-catenin signaling by CCAAT/enhancer binding protein β during adipogenesis.

    Obesity (Silver Spring). 2012;20(3):482-7.

    Abstract

    Activation of the Wnt/β-catenin signaling pathway inhibits adipogenesis, while disruption of Wnt signaling leads to spontaneous adipogenesis. CCAAT/enhancer binding protein β (C/EBPβ) is rapidly induced in early stages of adipogenesis and is responsible for transcriptional induction of two major adipogenic transcription factors, peroxisome proliferator-activated receptor γ (PPARγ) and C/EBPα. In this study, we examined whether C/EBPβ is involved in the suppression of Wnt/β-catenin signaling during adipogenesis. Knockdown of C/EBPβ expression not only inhibited adipogenesis but also maintained active Wnt/β-catenin signaling, after addition of adipogenic inducers. In contrast, overexpression of C/EBPβ substantially inhibited Wnt signaling. Interestingly, our data showed that C/EBPβ is involved in the expression of Wnt10b, a major Wnt ligand in preadipocytes, even though C/EBPβ is not an essential factor to regulate Wnt10b expression during adipogenesis, and that C/EBPβ inhibits Wnt10b promoter activity by directly binding to specific regions of the promoter. These results suggest a dual function of C/EBPβ: stimulating expression of adipogenic genes and inhibiting Wnt signaling.

    PubMed IF 4.9 내분비대사내과
25. 552012

    제1저자 오세원 · 교신저자 나기영

    Oh SW, Ahn JM, Lee YM, Kim S, Chin HJ, Chae DW, Na KY

    Activation of hypoxia-inducible factor by cobalt is associated with the attenuation of tissue injury and apoptosis in cyclosporine-induced nephropathy.

    Tohoku J Exp Med. 2012;226(3):197-206.

    Abstract

    Hypoxia-inducible factor (HIF) is a transcription factor that regulates cellular hypoxic responses. Despite the therapeutic benefits of cyclosporine A (CsA) in organ transplantation, its clinical use is limited due to chronic nephropathy. We investigated whether HIF activation by cobalt could improve CsA-induced nephropathy, and investigated the related mechanism. In animal experiments, rats were kept on a 0.05% low-salt diet and administered CsA subcutaneously for 28 days (15 mg/kg/day). They also received cobalt (10 mg/kg/day) during the entire experimental period. The administration of cobalt significantly increased HIF-1α expression in the kidney. The increased expression of HIF-1α ameliorated CsA-induced afferent arteriolopathy and tubulointerstitial injury in the kidney. Cobalt significantly reduced the infiltration of macrophages/monocytes into the renal tubulointerstitium. In addition, HIF activation by cobalt reduced the number of CsA-induced apoptotic cells in the kidney. Subsequently, HK-2 human renal tubular epithelial cells were used for in vitro experiments. They were pre-treated with 150 µM of cobalt to activate HIF, and then exposed to 10 µM CsA. HIF activation by cobalt decreased the CsA-induced apoptosis in HK-2 cells, as judged by the decreases in the number of apoptotic cells, pro-apoptotic caspase-3 activity, and the expression level of cleaved caspase-3, together with the increase in the expression of anti-apoptotic bcl-2. Cobalt pretreatment also reduced the CsA-induced phosphorylation of NF-κB and the CsA-induced expression of vimentin and α-smooth muscle actin, suggesting the attenuation of inflammation and fibrosis. In conclusion, the activation of HIF by cobalt may ameliorate the CsA-induced nephropathy by inhibiting apoptosis, inflammation, and fibrosis.

    PubMed IF 1.5 신장내과
26. 542012

    제1저자 신철민 · 교신저자 김나영

    Shin CM, Kim N, Park JH, Kang GH, Kim JS, Jung HC, Song IS

    Prediction of the risk for gastric cancer using candidate methylation markers in the non-neoplastic gastric mucosae.

    J Pathol. 2012;226(4):654-65.

    Abstract

    Aberrant DNA methylation is frequently found during gastric carcinogenesis. Recently, we identified potential methylation markers important for Helicobacter pylori-induced gastric carcinogenesis using an Illumina methylation chip assay. In this study, we evaluated the candidate genes as markers for gastric cancer (GC) in a large Korean population. DNA methylation of PTPN6, MOS, DCC, CRK, and VAV1 was evaluated in non-neoplastic gastric specimens using quantitative methylation-specific PCR in patients with GC (n = 207) and their age- and gender-matched controls (n = 207). Methylation levels in 125 GC samples were also compared. H. pylori infection status was categorized as negative, active, or past infection according to the results of endoscopy-based tests (CLOtest, histology, and culture), H. pylori serology, and serum pepsinogen test. In the controls, active H. pylori infection increased methylation levels in DCC, CRK, MOS, and VAV1 but decreased methylation levels in PTPN6 (all p < 0.05); the methylation levels in MOS remained increased in patients with past H. pylori infection compared to H. pylori-negative subjects (p < 0.001). Methylation levels in MOS in non-neoplastic gastric mucosae increased in the presence of GC, regardless of H. pylori infection status (p < 0.01). Methylation levels in all genes but DCC decreased significantly in GC specimens compared to neoplastic gastric mucosae (p < 0.01); however, methylation levels in GC tissues were not correlated with those in their background gastric mucosae. Hypomethylation of MOS in GC tissues was associated with tumour invasion, nodal metastasis, and undifferentiated histology (p < 0.05). To summarize, among the candidate genes, DNA methylation of MOS may reflect the duration of H. pylori exposure and may be a marker for the development of GC.

    PubMed IF 5.4 소화기내과
27. 532012

    제1저자 김혜진 · 교신저자 방영주

    Kim HJ, Kim HP, Yoon YK, Kim MS, Lee GS, Han SW, Im SA, Kim TY, Oh DY, Bang YJ

    Antitumor activity of HM781-36B, a pan-HER tyrosine kinase inhibitor, in HER2-amplified breast cancer cells.

    Anticancer Drugs. 2012;23(3):288-97.

    Abstract

    HM781-36B is an orally administered pan-human epidermal growth factor receptor (HER) inhibitor. To explore the role of pan-HER inhibitor in breast cancer, we investigated the antitumor effect and mechanisms of HM781-36B in breast cancer cell lines. Six breast cancer cell lines (BT474, MDA-MB-453, SK-BR-3, T47D, MCF-7, and MDA-MB-231) were tested. The growth inhibitory effect was assessed using the tetrazolium bromide [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide] assay. The cell cycle at various concentrations of HM781-36B was analyzed by flow cytometry, and analysis of downstream molecules was performed by western blot analysis. Interaction of HM781-36B with cytotoxic chemotherapeutic agents was analyzed by combination index using CalcuSyn. The HER2-amplified cells (SK-BR-3, BT474, and MDA-MB-453) were sensitive to HM781-36B (IC50=0.001 μmol/l, 0.0012 μmol/l, and 0.0095 μmol/l, respectively). HM781-36B induced G1 arrest and resulted in apoptosis. It reduced the level of p-HER2, p-AKT, p-ERK, and p-STAT3. HM781-36B combined with 5-fluorouracil, cisplatin, paclitaxel, or gemcitabine showed a synergistic inhibitory effect on the HER2-amplified and on some of the HER2-nonamplified breast cancer cells. HM781-36B could be a promising treatment for HER2-amplified breast cancer as a single agent or in combination with cytotoxic agents and can be a candidate for treatment of HER2-nonamplified breast cancer in combination with cytotoxic agents.

    PubMed IF 2 혈액종양내과
28. 522012

    제1저자 오홍상 · 교신저자 이동호

    Oh HS, Lee DH, Seo JY, Cho YR, Kim N, Jeoung SH, Kim JW, Hwang JH, Park YS, Lee SH, Shin CM, Cho HJ, Jung HC, Song IS

    Ten-day sequential therapy is more effective than proton pump inhibitor-based therapy in Korea: a prospective, randomized study.

    J Gastroenterol Hepatol. 2012;27(3):504-9.

    Abstract

    BACKGROUND AND AIMS The eradication rate of proton pump inhibitor (PPI)-based triple therapy for Helicobacter pylori (H. pylori) infection has decreased, mainly due to increasing antibiotic resistance, especially against clarithromycin. It has been reported that a 10-day sequential strategy can produce good outcomes. The aim of this prospective study was to assess the efficacy of sequential therapy as the first-line treatment for the eradication of H. pylori in Korea.

    METHODS A total of 116 patients with proven H. pylori infection received 10-day sequential therapy (20 mg rabeprazole and 1 g amoxicillin, twice daily for the first 5 days, followed by 20 mg rabeprazole, 500 mg clarithromycin, and 500 mg metronidazole, twice daily for the remaining 5 days); 130 patients received 7-day triple therapy (20 mg rabeprazole, 500 mg clarithromycin, and 1 g amoxicillin, twice daily for 7 days). Eradication was evaluated by the (13) C-urea breath test, 4 weeks after the completion of treatment. Compliance and adverse events were assessed.

    RESULTS The eradication rates of 10-day sequential therapy and PPI-based triple therapy were 79.3% (92/116) and 63% (82/130) by intention-to-treat analysis, respectively (P = 0.005), and 81.9% (91/111) and 64.5% (82/127) by per protocol analysis, respectively (P = 0.003). Mild adverse events occurred in both therapy groups (27.5% vs 23.8%), but both treatments were well tolerated.

    CONCLUSION The eradication rate of the 10-day sequential therapy regimen was significantly higher than that of PPI-based triple therapy in the Korean population. Ten-day sequential therapy might be effective as a first-line treatment for H. pylori infection in Korea.

    PubMed IF 3.5 소화기내과
29. 512012

    제1저자 김재환 · 교신저자 류지곤

    Kim J, Ryu JK, Ahn DW, Park JK, Yoon WJ, Kim YT, Yoon YB

    Results of repeat endoscopic retrograde cholangiopancreatography after initial biliary cannulation failure following needle-knife sphincterotomy.

    J Gastroenterol Hepatol. 2012;27(3):516-20.

    Abstract

    BACKGROUND AND AIM After failed biliary cannulation with needle knife sphincterotomy (NKS), endoscopic retrograde cholangiopancreatography (ERCP) is sometimes repeatedly performed in clinically stable patients; however, there are few reports about the results. This study assessed the results of repeated ERCPs after failure with NKS.

    METHODS After failed NKS, patients who underwent repeated ERCP for the same purpose within 3 days were retrospectively identified. Success was defined as deep placement of a catheter into the common bile duct.

    RESULTS Sixty-nine patients underwent a second ERCP procedure and, of those, six underwent a third ERCP. Of the 69 patients, cannulation was successful in 76.8% (53/69): 46 of 58 patients without additional NKS and 7 of 11 with additional NKS. Success increased to 79.7% (55/69) after the results of the third ERCP were included. Common causes of failed NKS were biliary deep cannulation failure (78.3%) and blocking of the endoscopic view due to bleeding (13.0%). There was a significant difference in success rates between the one day (65.7%) and the combined 2-3 day (88.2%) cases (P = 0.027). Except for the interval between ERCPs, there were no other factors associated with success rates. Complications occurred in 8, 11, and one patient after initial, second, and third ERCP and there was no difference of complication rates between each ERCPs.

    CONCLUSIONS In cases with biliary cannulation failure with NKS, it is more worthwhile repeating ERCP 2 or 3 days after such failure than one day after, if the patient's condition permits delay of procedure.

    PubMed IF 3.5 소화기내과
30. 502012

    제1저자 주경돈 · 교신저자 오국환

    Ju KD, Shin EK, Cho EJ, Yoon HB, Kim HS, Kim H, Yang J, Hwang YH, Ahn C, Oh KH

    Ethyl pyruvate ameliorates albuminuria and glomerular injury in the animal model of diabetic nephropathy.

    Am J Physiol Renal Physiol. 2012;302(5):F606-13.

    Abstract

    Pyruvate is an endogenous antioxidant and anti-inflammatory substance. The present study was implemented to investigate the protective effect of ethyl pyruvate (EP) against the development and progression of diabetic nephropathy in an in vivo and in vitro model. Diabetic rats were prepared by injecting streptozotocin (65 mg/kg). Those that developed diabetes after 72 h were treated with EP (40 mg/kg) intraperitoneally. Diabetic rats without pyruvate treatment and nondiabetic rats were used for control. As an in vitro experiment, rat mesangial cells cultured primarily from Sprague-Dawley rats were treated in high-glucose (HG; 50 mM) or normal-glucose (NG; 5 mM) conditions and with or without pyruvate. Pyruvate-treated diabetic rats exhibited decreased albuminuria and attenuated NADPH-dependent reactive oxygen species generation. Immunohistochemistry showed reduced laminin, type IV collagen, and fibronectin deposition in the glomeruli compared with nontreated diabetic rats. Parallel changes were shown in tissue mRNA and protein expression levels of monocyte chemoattractant protein-1, transforming growth factor-β1, laminin, fibronectin, and type IV collagen in the kidney. Concordantly, protective effects were also exhibited in the mesangial cell culture system. These findings suggest that pyruvate protects against kidney injury via NADPH oxidase inhibition. The present study established that activation of NADPH oxidase plays a crucial role in diabetes-induced oxidative stress, glomerular hypertrophy, and ECM molecule expression. Pyruvate exhibited a renoprotective effect in the progression of experimental diabetic nephropathy. Future research is warranted to investigate the protective mechanism of pyruvate more specifically in relation to NADPH oxidase in diabetic nephropathy.

    PubMed IF 3.6 신장내과

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