SCI 발표논문

1. 652010

   제1저자 이세원 · 교신저자 임재준/전경만

   Lee SW, Jang YS, Park CM, Kang HY, Koh WJ, Yim JJ, Jeon K

   The role of chest CT scanning in TB outbreak investigation.

   Chest. 2010;137(5):1057-64.

   Abstract

   BACKGROUND In TB outbreaks, detecting active cases is the key step in stopping transmission of the disease. The aim of this study was to evaluate the role of high-resolution CT (HRCT) scanning of the chest in the investigation of a TB outbreak that developed in a cohort of 92 soldiers in the South Korean army.

   METHODS Outbreak investigation, including tuberculin skin test (TST), QuantiFERON TB Gold In-Tube (QFT) test, and simple chest radiograph (CXR), was performed. For participants with any abnormal findings in these tests, HRCT scanning was done. Active pulmonary TB was diagnosed based on sputum studies or HRCT scan findings. In addition, participants with positive results in both TST and QFT were treated as having a latent TB infection (LTBI). TST and QFT were repeated in participants with a positive result in one of these tests. CXR was repeated in all participants at 3 and 6 months of follow-up.

   RESULTS Eighty-seven participants completed the study protocol. Among them, 18 active TB cases were diagnosed. Nine of these had normal CXR, but had lesions that were suggestive of active TB on HRCT scan. Twenty-two participants with normal HRCT scans and positive results with TST and QFT at initial investigation were treated as LTBI. Among 13 participants with normal CXR and positive results in either TST or QFT, nine completed a 3-month investigation. All but one of nine participants revealed positive results in both tests.

   CONCLUSION Inclusion of HRCT scanning in the outbreak investigation of TB may be helpful in differentiating active TB from LTBI more reliably.

   TRIAL REGISTRATION clinicaltrials.gov; Identifier: NCT00889759.

   PubMed IF 9.8 호흡기내과
2. 642010

   제1저자 박미영 · 교신저자 이춘택

   Park MY, Kim DR, Jung HW, Yoon HI, Lee JH, Lee CT

   Genetic immunotherapy of lung cancer using conditionally replicating adenovirus and adenovirus-interferon-beta.

   Cancer Gene Ther. 2010;17(5):356-64.

   Abstract

   Genetic immunotherapy is considered an ideal treatment modality for cancer because of its systemic nature. This study was designed to develop a potent novel genetic immunotherapy by combining conditionally replicating adenovirus (CRAd) and replication-defective adenovirus expressing interferon-beta (ad-IFN-beta). We investigated the efficacy of this therapy in an immunocompetent mouse tumor model. Transduction with CRAd (Delta24RGD) induced cytolysis in a mouse lung cancer cell line (Lewis lung carcinoma (LLC)). Combined transduction of ad-IFN-beta and Delta24RGD in the LLC cells induced a greater and more prolonged production of IFN-beta. Media transfer from the LLC-Delta24RGD-ad-IFN-beta to untransduced LLC cells induced the production of IFN-beta; these results confirmed the replication and release of ad-IFN-beta. LLC cells transduced with ad-IFN-beta and Delta24RGD had decreased tumorigenicity in syngeneic mice. Tumor vaccination with irradiated LLC-ad-IFN-beta-Delta24RGD showed a significant increase in the survival of tumor-bearing syngeneic mice compared with mice with a single transduced LLC vaccination; this was mediated by an enhanced cytotoxic T-lymphocyte response against the LLC cells. The results of this study showed that cotransduced Delta24RGD to ad-IFN-beta aided the replication of ad-IFN-beta in the LLC cells. A high local concentration of IFN-beta and local release of tumor antigen by CRAd induced strong antitumor immunity. This combination strategy might provide a powerful means by which ad-cytokines and CRAd can be combined and other adenoviruses expressing different cytokines might also be used.

   PubMed IF 6.4 호흡기내과
3. 632010

   제1저자 김지현 · 교신저자 방영주

   Kim JH, Lee KW, Kim YH, Lee KH, Oh DY, Kim J, Yang SH, Im SA, Choi SH, Bang YJ

   Individualized tumor response testing for prediction of response to Paclitaxel and Cisplatin chemotherapy in patients with advanced gastric cancer.

   J Korean Med Sci. 2010;25(5):684-90.

   Abstract

   The purpose of our study was to determine the most accurate analytic method to define in vitro chemosensitivity, using clinical response as reference standard in prospective clinical trial, and to assess accuracy of adenosine triphosphate-based chemotherapy response assay (ATP-CRA). Forty-eight patients with chemo-naïve, histologically confirmed, locally advanced or metastatic gastric cancer were enrolled for the study and were treated with combination chemotherapy of paclitaxel 175 mg/m(2) and cisplatin 75 mg/m(2) for maximum of six cycles after obtaining specimen for ATP-CRA. We performed the receiver operator characteristic curve analysis using patient responses by WHO criteria and ATP-CRA results to define the method with the highest accuracy. Median progression free survival was 4.2 months (95% confidence interval [CI]: 3.4-5.0) and median overall survival was 11.8 months (95% CI: 9.7-13.8) for all enrolled patients. Chemosensitivity index method yielded highest accuracy of 77.8% by ROC curve analysis, and the specificity, sensitivity, positive and negative predictive values were 95.7%, 46.2%, 85.7%, and 75.9%. In vitro chemosensitive group showed higher response rate (85.7% vs. 24.1%) (P=0.005) compared to chemoresistant group. ATP-CRA could predict clinical response to paclitaxel and cisplatin chemotherapy with high accuracy in advanced gastric cancer patients. Our study supports the use of ATP-CRA in further validation studies.

   PubMed IF 3.2 혈액종양내과
4. 622010

   제1저자 김민주 · 교신저자 김인호

   Kim MJ, Kim I, Bae HM, Seo K, Park N, Yoon SS, Park S, Kim BK

   Hematopoietic stem cell transplantation after posttransplant lymphoproliferative disorder.

   J Korean Med Sci. 2010;25(5):781-4.

   Abstract

   A 16-yr-old girl received liver transplantation for fulminant hepatitis. Aplastic anemia developed, and she received hematopoietic stem cell transplantation (HSCT). Eleven months after liver transplantation, abdominal lymph node enlargement and colon ulcers were observed, and colon biopsy showed posttransplant lymphoproliferative disorder (PTLD). Immunosuppression reduction was attempted, but it produced no therapeutic effect. Fourteen months after liver transplantation, she received a second HSCT due to engraftment failure, and PTLD resolved completely. The second HSCT can serve as cellular therapy for PTLD.

   PubMed IF 3.2 혈액종양내과
5. 612010

   제1저자 박효은 · 교신저자 오세일

   Park HE, Kim KH, Kim KB, Ahn H, Choi YS, Oh S

   Characteristics of P wave in patients with sinus rhythm after maze operation.

   J Korean Med Sci. 2010;25(5):712-5.

   Abstract

   Maze operation could alter P wave morphology in electrocardiogram (ECG), which might prevent exact diagnosis of the cardiac rhythm of patients. However, characteristics of P wave in patients with sinus rhythm after the operation have not been elucidated systematically. Consecutive patients who underwent the modified Cox Maze operation from January to December 2007 were enrolled. The standard 12-lead ECG and echocardiography were evaluated in patients who had sinus rhythm at 6 months after the operation. The average axis of P wave was 65+/-30 degrees. The average amplitude of P wave was less than 0.1 mV in all 12-leads, with highest amplitude in V(1). The most common morphology of P wave was monophasic with positive polarity (49%), except aVR lead, which was different from those in patients with enlarged left atrium, characterized by large P-terminal force in the lead V(1). There were no significant differences in P-wave characteristics and echocardiographic parameters between patients with LA activity (30.6%) versus without LA activity (69.4%) at 6 months after the operation. In conclusion, the morphology of P wave in patients after Maze operation shows loss of typical ECG pattern of P mitrale: P wave morphology is small in amplitude, monophasic and with positive polarity.

   PubMed IF 3.2 순환기내과
6. 602010

   제1저자 오국환 · 교신저자 안규리

   Oh KH, Jung JY, Yoon MO, Song A, Lee H, Ro H, Hwang YH, Kim DK, Margetts P, Ahn C

   Intra-peritoneal interleukin-6 system is a potent determinant of the baseline peritoneal solute transport in incident peritoneal dialysis patients.

   Nephrol Dial Transplant. 2010;25(5):1639-46.

   Abstract

   BACKGROUND Interleukin-6 (IL-6) is a key player in modulating inflammation. IL-6 and soluble IL-6 receptor (sIL-6R) complex induces the synthesis and secretion of various chemokines, adhesion molecules and angiogenic molecules. We hypothesized that the baseline peritoneal solute transport rate (PSTR) early after commencing peritoneal dialysis (PD) may depend largely on the IL-6/sIL-6R system. We also hypothesized that the dialysate concentrations of IL-6/sIL-6R could be closely related to local inflammation or angiogenesis in the peritoneal cavity.

   METHODS Fifty incident patients with a modified peritoneal equilibration test result within 3 months after commencing PD and without a previous history of peritonitis were enrolled. Clinical parameters such as age, sex, comorbid disease, body mass index, residual renal function and C-reactive protein were assessed. Serum and dialysate markers including CA125, IL-6, sIL-6R, monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) were measured and correlated with PSTR.

   RESULTS Dialysate concentrations of IL-6 (r = 0.576, P < 0.001), MCP-1 (r = 0.408, P = 0.003) and Ang-2 (r = 0.408, P = 0.003) correlated with mass transfer area coefficient for creatinine (MTAC(cr)), respectively. Dialysate appearance rate (AR) of albumin correlated with dialysate concentrations of CA125 (r = 0.751, P < 0.001), IL-6 (r = 0.303, P = 0.039), sIL-6R (r = 0.497, P < 0.001), MCP-1 (r = 0.488, P < 0.001), VEGF (r = 0.443, P = 0.004) and Ang-2 (r = 0.488, P < 0.001). Neither MTAC(cr) nor AR of albumin was associated with systemic markers. Multivariate analysis showed that MTAC(cr) is independently associated with dialysate IL-6 and serum albumin. It also showed that AR of albumin is independently predicted by dialysate sIL-6R. Dialysate IL-6 correlated with dialysate concentrations of CA125 MCP-1, VEGF and Ang-2.

   CONCLUSION Our study from incident PD patients suggested that (i) dialysate the IL-6 system is a potent determinant of baseline PSTR and (ii) elevation of IL-6 in the dialysate is associated with up-regulation of intra-peritoneal inflammatory and angiogenic molecules.

   PubMed IF 8.3 신장내과
7. 592010

   제1저자 진호준 · 교신저자 채동완

   Chin HJ, Fu YY, Ahn JM, Na KY, Kim YS, Kim S, Chae DW

   Omacor, n-3 polyunsaturated fatty acid, attenuated albuminuria and renal dysfunction with decrease of SREBP-1 expression and triglyceride amount in the kidney of type II diabetic animals.

   Nephrol Dial Transplant. 2010;25(5):1450-7.

   Abstract

   BACKGROUND We assumed that n-3 polyunsaturated fatty acid (n-3 PUFA) would attenuate the tissue dyslipidemic condition through suppression of sterol regulatory element-binding protein (SREBP-1) in the kidney and would prevent renal progression in diabetic animals.

   METHODS We gavaged Omacor, composed of docosahexaenoic acid and eicosapentaenoic acid, to db/db mice for 2 weeks (0.2 g/100 g/day). We measured the markers of renal function, triglyceride amount and expressions of SREBP-1, liver X-activated receptor alpha (LXRalpha), collagen IV and TGFbeta-1 in kidney lysate, and performed immunohistochemical staining for SREBP-1, desmin and WT-1 in the renal sections. We measured collagen IV in primary mesangial cells cultured with high glucose media (25 mM), both with and without a transient transfection of small interfering RNA (siRNA) SREBP-1.

   RESULTS Omacor decreased the concentration of serum free fatty acid, and the amount of renal triglyceride, which was associated with decreased expression of SREBP-1 in the kidney, albuminuria and renal dysfunction in db/db mice. Omacor attenuated the expansion of mesangial matrix and the expression of desmin, preserved the WT-1 positive cells, and inhibited the phosphorylation of nuclear factor kappaB in renal tissue. In mesangial cells cultured in high glucose media, the suppression of SREBP-1 expression decreased the collagen IV in the cells.

   CONCLUSIONS Our study results demonstrated that n-3 PUFA prevented renal progression with attenuation of SREBP-1 and reduction of triglyceride in the diabetic kidney. This suggests that the regulation of dyslipidemic signals in the kidney could be a possible mechanism by which PUFA preserves renal function in the diabetic condition.

   PubMed IF 8.3 신장내과
8. 582010

   제1저자 박효은 · 교신저자 김형관

   Park HE, Chang SA, Kim HK, Shin DH, Kim JH, Seo MK, Kim YJ, Cho GY, Sohn DW, Oh BH, Park YB

   Impact of loading condition on the 2D speckle tracking-derived left ventricular dyssynchrony index in nonischemic dilated cardiomyopathy.

   Circ Cardiovasc Imaging. 2010;3(3):272-81.

   Abstract

   BACKGROUND The effects of left ventricular (LV) loading conditions on LV dyssynchrony have not been elucidated. We modified LV loading conditions to reveal their effects on echocardiography-derived LV dyssynchrony index (LVdys) in patients with documented nonischemic dilated cardiomyopathy.

   METHODS AND RESULTS Thirty-seven patients were consecutively enrolled. After baseline measurements, pneumatic compression of the lower extremities (Pcom) was used to increase LV afterload. Subsequently, sublingual nitroglycerin (SL-NG) was administered to modify preload. Conventional echocardiographic parameters, LVdys (by speckle-tracking radial strain analysis) and LV end-systolic wall stress (LV-ESWS), were calculated under each condition. LVdys-6 (defined as the maximal difference in time-to-peak radial strain between 6 myocardial segments) and LV-ESWS increased under Pcom (for LVdys-6, 159+/-117 at baseline versus 239+/-140 ms under Pcom, P<0.05; for LV-ESWS, 191+/-63 versus 228+/-80 g/m(2), P<0.05) After SL-NG application, both parameters decreased significantly (for LVdys-6, 239+/-140 under Pcom versus 147+/-103 ms after SL-NG, P<0.05; for LV-ESWS, 228+/-80 under Pcom versus 189+/-67 g/m(2) after SL-NG, P<0.05). When the presence of LV dyssynchrony was defined as the absolute difference in time-to-peak radial strain between the anteroseptal and posterior segments (LVdys-2), the results were unchanged. Using 130 ms as a cutoff value, the proportion of patients with LV dyssynchrony changed significantly (29.7% at baseline, 45.9% under Pcom, and 35.1% after SL-NG). When the presence of LV dyssynchrony was defined as standard deviation of the time to peak radial strain for 6 segments (LVdys-SD), the results were same. LVdys and LV-ESWS showed a modest but significant association with each other (r=0.47, P<0.001 for LVdys-6; r=0.41, P<0.001 for LVdys-2; r=0.46, P<0.001 for LVdys-SD).

   CONCLUSIONS To the best of our knowledge, the present study provides the first evidence of a significant association between LVdys and LV loading status, reflective of a dynamic nature of LVdys. Accordingly, LV loading conditions should be taken into account when echocardiographic LVdys is used for clinical decision-making of selecting candidates for cardiac resynchronization therapy or when it is used as a surrogate marker of prognosis.

   PubMed IF 9.1 순환기내과
9. 572010

   제1저자 정성수 · 교신저자 박경수

   Chung SS, Ahn BY, Kim M, Choi HH, Park HS, Kang S, Park SG, Kim YB, Cho YM, Lee HK, Chung CH, Park KS

   Control of adipogenesis by the SUMO-specific protease SENP2.

   Mol Cell Biol. 2010;30(9):2135-46.

   Abstract

   Here, we demonstrate that SENP2, a desumoylating enzyme, plays a critical role in the control of adipogenesis. SENP2 expression was markedly increased upon the induction of adipocyte differentiation, and this increase was dependent on protein kinase A activation. Remarkably, knockdown of SENP2 led to a dramatic attenuation of adipogenesis with a marked decrease in PPARgamma and C/EBPalpha mRNA levels. Knockdown of SENP2 also caused a marked reduction in the level of C/EBPbeta protein but not in that of C/EBPbeta mRNA. Interestingly, sumoylation of C/EBPbeta dramatically increased its ubiquitination and destabilization, and this increase could be reversed by SENP2. In addition, overexpression of C/EBPbeta could overcome the inhibitory effect of SENP2 knockdown on adipogenesis. Furthermore, SENP2 was absolutely required for adipogenesis of preadipocytes implanted into mice. These results establish a critical role for SENP2 in the regulation of adipogenesis by desumoylation and stabilization of C/EBPbeta and in turn by promoting the expression of its downstream effectors, such as PPARgamma and C/EBPalpha.

   PubMed IF 2.8 내분비대사내과
10. 562010

    제1저자 Alisher E. · 교신저자 김나영

    Eshmuratov A, Nah JC, Kim N, Lee HS, Lee HE, Lee BH, Uhm MS, Park YS, Lee DH, Jung HC, Song IS

    The correlation of endoscopic and histological diagnosis of gastric atrophy.

    Dig Dis Sci. 2010;55(5):1364-75.

    Abstract

    PURPOSE Gastric atrophy is a premalignant condition. The aim of this study was to evaluate the correlation between histological and endoscopic findings of atrophy, and to analyze the affecting factors.

    METHODS Atrophy was graded by endoscopy, and biopsy was performed in the antrum and body for the diagnosis of atrophy according to the Sydney system in the 1,330 subjects.

    RESULTS Both endoscopic and histological atrophy increased in proportion to age (P < 0.001). The prevalence of endoscopic atrophy was significantly lower than that of histological atrophy especially below 50 years of age. The sensitivity and specificity of endoscopy for the diagnosis of atrophy based on histological diagnosis of atrophy were 61.5 and 57.7% in the antrum, and were 46.8 and 76.4% in the body of the stomach. Multivariate analysis showed that an age <50 (OR 0.38, 95% CI 0.25-0.61) and a PG I/II ratio >3 (OR 0.50, 95% CI 0.35-0.71) in the antrum, and an age < 50 (OR 0.43, 95% CI 0.19-1.00) and a CRP > 5 mg/dl (OR 0.53, 95% CI 0.30-0.94) decreased the sensitivity of the endoscopic diagnosis of atrophy in the body.

    CONCLUSIONS A high index of suspicion of gastric atrophy is important in the young age group, and confirmation of the diagnosis by histology is necessary.

    PubMed IF 2.8 소화기내과
11. 552010

    제1저자 박영식 · 교신저자 양석철

    Park YS, Kim SH, Park SK, Park BJ, Kim YT, Lee SM, Yim JJ, Yoo CG, Kim YW, Han SK, Shim YS, Yang SC

    Costs for 5-year lung cancer survivors in a tertiary care hospital in South Korea.

    Lung Cancer. 2010;68(2):299-304.

    Abstract

    INTRODUCTION As the population of patients with lung cancer increases, the expenditure on lung cancer treatment will become a huge economic burden in many countries. To support public health services for the treatment of lung cancer, the calculation of lung cancer-specific costs is important.

    METHODS This study included newly diagnosed 76 lung cancer patients who had survived for at least 5 years after the diagnosis in a tertiary care hospital in South Korea. Direct medical costs were calculated from health care claims obtained from Seoul National University Hospital, which included out-of-pocket expenditures. Direct non-medical and indirect costs were calculated from national statistics.

    RESULTS Mean direct medical costs, direct non-medical costs, and indirect costs amounted to $21,321, $6444 and $4943 respectively, based on an exchange rate of Korean Won 1200=US $1. The average cost for treatment of one lung cancer patient for all 5 years was $32,708. This constituted 44.7% of the per capita income during the same 5-year period.

    CONCLUSION The economic burden of lung cancer treatment is significant in Korea.

    PubMed IF 5.3 호흡기내과
12. 542010

    제1저자 박혜인조 · 교신저자 오윤규

    Park HC, Yoon HB, Son MJ, Jung ES, Joo KW, Chin HJ, Oh KH, Lim CS, Kim YS, Ahn C, Han JS, Kim S, Hahm BJ, Oh YK

    Depression and health-related quality of life in maintenance hemodialysis patients.

    Clin Nephrol. 2010;73(5):374-80.

    Abstract

    BACKGROUND This study was designed to determine the prevalence of depression among hemodialysis (HD) patients from urban hospitals in Korea, to illustrate demographic factors and biomarkers associated with depression and health-related quality of life (HRQOL), and to demonstrate association between depression and HRQOL.

    PATIENTS AND METHODS For this multicenter, cross-sectional study, 160 HD patients from 3 university teaching hospitals and 3 local dialysis units in Korea were enrolled. Korean Beck's depression inventory and Korean version of Kidney Disease Quality of Life short form, version 1.3 (KDQOL-SFTM 1.3) were used to evaluate depression and quality of life, respectively.

    RESULTS Depression was found in 51 out of 160 (31.9%) patients. Old age (> 60 years old), low hemoglobin level (< 10 g/dl), and low economic status were associated with depression, and old age (OR 6.138, p = 0.001) was the most important risk factor among them. Old age, female gender, presence of diabetes mellitus, high comorbidity index score (modified Charlson comorbidity index > or = 6), hypoalbuminemia (< 4.0 g/dl), and high CRP (> 0.5 mg/dl) were common factors associated with decreased HRQOL. Depression and HRQOL showed inverse linear relationship.

    CONCLUSIONS Moderate to severe depression was common in maintenance HD patients in Korea. Among factors associated with depression and decreased HRQOL, some characteristics are potentially modifiable by social and medical intervention. Further prospective studies are warranted to see whether depression and HRQOL can be improved by modifying these factors.

    PubMed IF 0.8 신장내과
13. 532010

    제1저자 박효은 · 교신저자 구본권

    Park HE, Koo BK, Lee W, Cho Y, Park JS, Choi JY, Jeong MH, Kim JH, Chae SC, Kim YJ, Nam CW, Lee JH, Choi DH, Hong TJ, Chae JK, Rhew JY, Kim KS, Kim HS, Oh BH, Park YB, KAMIR investigators

    Periodic variation and its effect on management and prognosis of Korean patients with acute myocardial infarction.

    Circ J. 2010;74(5):970-6.

    Abstract

    BACKGROUND The characteristics of the periodic variation in acute myocardial infarction (AMI) and the subsequent effect on management and prognosis have not been fully investigated in a large number of Asian populations.

    METHODS AND RESULTS From a prospective, observational multicenter online registry, 4,573 patients diagnosed as AMI in Korea from January to December 2006 were included. The highest incidence of AMI was between 8 a.m. and noon. The number of cases was highest in the winter and lowest in the autumn (13.6 vs 11.4 patients per day, P<0.001). Patients with symptom onset during working hours had a shorter time to first medical contact (203+/-288 min) compared with out-of-hours onset (230+/-288 min, P=0.003). In patients who underwent primary angioplasty, out-of hours symptom onset was associated with a greater time delay in both the patient's and the medical facility's response (door-to-balloon time out-of hours vs working hours: 101+/-54 min vs 84+/-44 min, P<0.001). In patients with ST-segment elevation myocardial infarction, symptoms to first medical contact showed a significant relationship to in-hospital mortality (for every 10 min of symptoms to first medical contact, odds ratio 1.006, 95% confidence interval 1.001-1.012, P=0.018)

    CONCLUSIONS Circadian and periodic variation in AMI exists in Korean patients, which resulted in different patient behavior, hospital management and outcomes.

    PubMed IF 5.8 순환기내과
14. 522010

    제1저자 장성아 · 교신저자 손대원

    Chang SA, Kim HK, Kim YJ, Cho GY, Oh S, Sohn DW

    Role of pericardium in the maintenance of left ventricular twist.

    Heart. 2010;96(10):785-90.

    Abstract

    BACKGROUND The role of pericardium in left ventricular (LV) twist has not been directly investigated. We sought to determine the role of pericardium in maintenance of LV twist function in an animal experiment, before and after pericardial opening.

    METHODS 13 mongrel dogs were initially operated on, but two dogs were excluded from the final analyses owing to poor speckle tracking. Intraoperative echocardiography for conventional and speckle tracking measurements was performed at baseline with intact pericardium, and after pericardial opening. Using the speckle tracking technique, LV twist and strains were obtained before and after pericardial opening in 11 animals and additionally after pericardial repair in five animals.

    RESULTS LV twist was significantly decreased after pericardial opening (10.1 degrees (5.1 degrees ) to 7.4 degrees (6.4 degrees ), p=0.001). LV twist and untwist rate were also decreased (115.0 degrees (99.6 degrees )/s to 66.7 degrees (42.5 degrees )/s for twist rate, -127.6 degrees (74.3 degrees )/s to -84.2 degrees (734 degrees )/s for untwist rate, p=0.015 and 0.009, respectively). LV stroke volume and ejection fraction were similar irrespective of pericardial opening, but radial strain measured at the mid ventricular level was significantly increased (31.7% (17.4%) to 32.3% (24.0%), p=0.02) after pericardial opening without changes in circumferential and longitudinal strains. LV twist degree was restored after pericardial repair.

    CONCLUSION The pericardium is an important structure for maintaining LV twist. Given no significant impact of the presence or absence of pericardium on LV systolic performance, an increase in LV radial strain serves as a compensatory mechanism to preserve LV systolic function despite a decrease in LV twist in the absence of pericardium.

    PubMed IF 4.4 순환기내과
15. 512010

    제1저자 우현구 · 교신저자 김윤준

    Woo HG, Lee JH, Yoon JH, Kim CY, Lee HS, Jang JJ, Yi NJ, Suh KS, Lee KU, Park ES, Thorgeirsson SS, Kim YJ

    Identification of a cholangiocarcinoma-like gene expression trait in hepatocellular carcinoma.

    Cancer Res. 2010;70(8):3034-41.

    Abstract

    Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major adult liver cancers. The existence of combined hepatocellular-cholangiocarcinoma (CHC), a histopathologic intermediate form between HCC and CC, suggests phenotypic overlap between these tumors. Here, we applied an integrative oncogenomic approach to address the clinical and functional implications of the overlapping phenotype between these tumors. By performing gene expression profiling of human HCC, CHC, and CC, we identified a novel HCC subtype, i.e., cholangiocarcinoma-like HCC (CLHCC), which expressed cholangiocarcinoma-like traits (CC signature). Similar to CC and CHC, CLHCC showed an aggressive phenotype with shorter recurrence-free and overall survival. In addition, we found that CLHCC coexpressed embryonic stem cell-like expression traits (ES signature) suggesting its derivation from bipotent hepatic progenitor cells. By comparing the expression of CC signature with previous ES-like, hepatoblast-like, or proliferation-related traits, we observed that the prognostic value of the CC signatures was independent of the expression of those signatures. In conclusion, we suggest that the acquisition of cholangiocarcinoma-like expression traits plays a critical role in the heterogeneous progression of HCC.

    PubMed IF 22.6 소화기내과
16. 502010

    제1저자 강희경 · 교신저자 김연수

    Kang HG, Lee JE, Yang SH, Lee SH, Gao W, Strom TB, Oh K, Lee DS, Kim YS

    Donor-strain-derived immature dendritic cell pre-treatment induced hyporesponsiveness against allogeneic antigens.

    Immunology. 2010;129(4):567-77.

    Abstract

    The maturation of antigen-presenting dendritic cells (DCs) serves as an important determinant for the regulation of immunity, and overall immune response. We hypothesized that a reduced immune response to donor alloantigens and improved allograft survival could be induced by pre-treating recipients with bone-marrow-derived donor-strain fixed immature DCs (FIDCs). Donor-strain-derived mature and immature DCs were fixed before grafting to ensure that they possessed a stable immunogenic phenotype. The fixed mature DCs effectively induced allogeneic T-cell proliferation in recipients, whereas FIDCs were unable to elicit an allogeneic T-cell response. T cells that had previously been exposed to FIDCs maintained naïve phenotypes and were unable to extensively divide after injection into lethally irradiated donor-strain mice. The pre-treatment of recipients with donor-strain FIDCs markedly prolonged the survival of islet as well as skin allografts. However, T-cell hyporesponsiveness induced by FIDC injection was abrogated by the depletion of CD4(+) CD25(+) T cells. Consequently, FIDC-induced T-cell hyporesponsiveness could reflect anergy rather than specific deletion. Our findings suggest that FIDCs of donor strain could be used to induce long-term graft survival.

    PubMed IF 5.4 신장내과
17. 492010

    제1저자 권정희 · 교신저자 이동호

    Kwon JH, Lee DH, Song BJ, Lee JW, Kim JJ, Park YS, Kim N, Jeong SH, Kim JW, Lee SH, Hwang JH, Jung HC, Song IS

    Ten-day sequential therapy as first-line treatment for Helicobacter pylori infection in Korea: a retrospective study.

    Helicobacter. 2010;15(2):148-53.

    Abstract

    BACKGROUND AND AIMS The eradication rate of proton-pump inhibitor-based triple therapy for Helicobacter pylori infection is low due to increasing antibiotics resistance, especially clarithromycin. Recently, it was reported in Europe that a 10-day sequential strategy produced good outcomes. The aim of this study was to assess the efficacy of sequential therapy as first-line treatment for eradication of H. pylori in clinical practice in Korea.

    MATERIALS AND METHODS A total of 98 patients (mean age 55.2 years and male 47, female 51) with proven H. pylori infection received 10-day sequential therapy (20 mg of rabeprazole, and 1 g of amoxicillin, twice daily for the first 5 days, followed by 20 mg of rabeprazole, 500 mg of clarithromycin, and 500 mg of metronidazole, twice daily for the remaining 5 days). Eradication was evaluated 4 weeks later, after completion of treatment by 13(C)-urea breath testing. Eradication rates were calculated by intention-to-treat (ITT) and by per protocol (PP). Compliance and adverse events were also assessed in study group.

    RESULTS The eradication rate of sequential therapy was 91.8% (90/98) by ITT and same result was reported by PP analysis (89/97). The study group consisted of 66 H. pylori associated gastritis, 7 gastric ulcer, and 25 duodenal ulcer patients (67.3%, 7.1%, 25.5%, respectively). Mild adverse events happened frequently (21.4%) but the treatment was well tolerable. The most common adverse event was a bitter taste (9.2%) followed by nausea and diarrhea (4.1%).

    CONCLUSIONS Ten-day sequential therapy is found to effectively eradicate H. pylori infection as first-line treatment in Korea.

    PubMed IF 4.6 소화기내과
18. 482010

    제1저자 임수 · 교신저자 장학철

    Lim S, Yoon JW, Choi SH, Park YJ, Lee JJ, Park JH, Lee SB, Kim KW, Lim JY, Kim YB, Park KS, Lee HK, Cho SI, Jang HC

    Combined impact of adiponectin and retinol-binding protein 4 on metabolic syndrome in elderly people: the Korean Longitudinal Study on Health and Aging.

    Obesity (Silver Spring). 2010;18(4):826-32.

    Abstract

    The prevalence of metabolic syndrome (MS) increases with progressing and is potentially associated with changes in adipose-derived cytokines, including adiponectin and retinol-binding protein 4 (RBP4). We aimed to determine the prevalence of MS, and the relationships between these factors and MS in elderly people. A population-based cohort study, the Korean Longitudinal Study on Health and Aging (KLoSHA), was performed on subjects aged > or =65 years by random stratified sampling in 2005-2006 (439 men and 561 women). Anthropometrics, biochemical factors including adiponectin and RBP4 levels, body composition, and abdominal fat by computed tomography (CT) were measured. The prevalence of MS was 61.0% in women and 39.9% in men. After adjustment for age, gender, smoking, alcohol, and exercise status and muscle mass, participants with the lowest quartile of adiponectin had a higher risk for having MS than those with the highest quartile (odds ratio (OR) = 4.12, P < 0.01). Similarly, subjects with the highest quartile of RBP4 showed an increased risk for having MS (OR = 1.73, P < 0.01). When both the lowest adiponectin and the highest RBP4 quartiles were combined, the OR increased to 6.22 compared with the opposite quartiles (i.e., highest adiponectin and lowest RBP4 concentrations). Furthermore, circulating levels of adiponectin and RBP4 were significantly correlated with visceral fat and insulin resistance index. In this study, the increased prevalence of MS in elderly but relatively lean population was associated with low adiponectin and high RBP4 levels. The combination of these factors might predict older subjects at high risk for having MS.

    PubMed IF 4.9 내분비대사내과
19. 472010

    제1저자 이철환 · 교신저자 김효수

    Lee CW, Baek SH, Hong TJ, Choi YJ, Kim YJ, Ahn TH, Ihm SH, Bae JH, Hong SJ, Kim DI, Ahn YK, Hur SH, Park DG, Choi DJ, Lee SU, Kim BS, Ryu KH, Jang YS, Lee SH, Seung KB, Kim HS

    A multicenter, eight-week treatment, single-step titration, open-label study assessing the percentage of Korean dyslipidemic patients achieving LDL cholesterol target with atorvastatin starting doses of 10 mg, 20 mg and 40 mg.

    Cardiovasc Drugs Ther. 2010;24(2):181-8.

    Abstract

    BACKGROUND This study was designed to evaluate the safety and efficacy of algorithm-based atorvastatin therapy initiated at different starting doses of 10, 20, and 40 mg in Korean dyslipidemic patients.

    METHODS Five hundred seventy-four patients were screened, and 425 were enrolled (low risk, n = 29; intermediate risk, n = 45; high risk, n = 351). The starting dose depended on a patient's cardiovascular risk and LDL-cholesterol (LDL-C) levels.

    RESULTS Of the patients, 253 (59.5%), 63 (14.8%) and 109 (25.6%) patients were assigned at baseline to 10 mg, 20 mg and 40 mg atorvastatin, respectively. 390 patients (91.8%) completed the study, and 35 discontinued prematurely. No patient in the low or intermediate risk groups was titrated to 80 mg at Week 4, whereas, 26 in the high risk group were. 81.9% of patients achieved their LDL-C target at Week 4, which was sustained through to Week 8 (86.0%). 89.1% of patients who were not titrated achieved their LDL-C target at Week 8, and 82.1% of patients who were titrated 1 step up achieved their LDL-C target at Week 8. Overall, about 40% reduction in LDL-C, non-HDL-C levels, and LDL-C/HDL-C ratio was observed during the follow-up. Triglyceride was reduced by approximately 10% by Week 8. HDL cholesterol was slightly increased over 8 weeks (2.6%). Atorvastatin was well tolerated at all dose levels.

    CONCLUSIONS Patient-tailored statin therapy according to an individual's risk category and LDL-C levels was safe and effective with a quick achievement of LDL-C target in Korean dyslipidemic patients.

    PubMed IF 3.5 순환기내과
20. 462010

    제1저자 윤원재 · 교신저자 윤용범

    Yoon WJ, Yoon YB, Kim YJ, Ryu JK, Kim YT

    Primary pancreatic lymphoma in Korea--a single center experience.

    J Korean Med Sci. 2010;25(4):536-40.

    Abstract

    The aim of this study was to report a single center experience of primary pancreatic lymphoma (PPL) in Korea. We analyzed the clinicopathological data from four PPL patients (three male, median age 36 yr) diagnosed from 1997 to 2007 at Seoul National University Hospital. The diagnoses were: diffuse large B cell lymphoma (n=2), Ki-1 (+) anaplastic large cell lymphoma (n=1), and Burkitt lymphoma (n=1). Presenting symptoms and signs were: abdominal pain (n=4), pancreatitis (n=2), weight loss (n=2) and abdominal mass (n=1). No patient underwent surgery. The Ann Arbor stages of the patients were: IEA (n=1), IIEA (n=1), and IVEB (n=2). Two patients underwent treatment. The stage IEA patient underwent chemotherapy and radiation therapy that resulted in a complete remission. The stage IVEB patient who underwent chemotherapy relapsed. This patient underwent subsequent peripheral blood stem cell transplantation and is alive at 30 months. Two patients (stages IVEB and IIEA) without treatment died at 0.8 and 7.0 months, respectively. For PPL patients, chemotherapy-based treatment, and addition of radiation therapy, if possible, may offer good prognosis.

    PubMed IF 3.2 소화기내과
21. 452010

    제1저자 박종선 · 교신저자 이재호

    Park JS, Kang YA, Kwon SY, Yoon HI, Chung JH, Lee CT, Lee JH

    Nested PCR in lung tissue for diagnosis of pulmonary tuberculosis.

    Eur Respir J. 2010;35(4):851-7.

    Abstract

    Diagnosis of pulmonary tuberculosis (TB) is difficult in cases with an unusual presentation and often requires a lung biopsy. The goal of this study was to determine the clinical usefulness of nested PCR on lung tissue for the diagnosis of pulmonary TB. Clinical and laboratory data were reviewed from patients who underwent diagnostic lung biopsies, followed by nested TB PCR on formalin-fixed paraffin-embedded lung tissue specimens. The diagnostic yield and clinical impact of nested PCR were investigated. Of the 223 patients studied, 142 were diagnosed with TB. Microbiologically confirmed TB was identified in 71 patients. Compared to culture results, the sensitivity, specificity, positive predictive value and negative predictive value of nested PCR were 85%, 99%, 98% and 88%, respectively. Nested PCR was more sensitive than acid-fast bacilli smear of respiratory specimens and histopathological findings. The PCR results provided an early diagnosis and initiation of treatment for TB. However, negative PCR results did not lead to discontinuation of unnecessary TB treatment in patients on medication. In conclusion, nested PCR on lung tissue specimens is a useful diagnostic test for pulmonary TB in patients with an unusual presentation.

    PubMed IF 23.8 호흡기내과
22. 442010

    제1저자 윤영광 · 교신저자 김태유

    Yoon YK, Kim HP, Han SW, Oh DY, Im SA, Bang YJ, Kim TY

    KRAS mutant lung cancer cells are differentially responsive to MEK inhibitor due to AKT or STAT3 activation: implication for combinatorial approach.

    Mol Carcinog. 2010;49(4):353-62.

    Abstract

    KRAS is frequently mutated in nonsmall cell lung cancer (NSCLC), resulting in the activation of the MAPK/ERK kinase (MEK)/ERK pathway. High-throughput mutation profile has shown that lung cancer frequently harbors comutation of cancer-related genes. Therefore, given that cancer cells have multiple genetic alterations, combinatorial therapeutic strategy is demanded for effective cancer therapy. To address this, we first characterized MEK dependence in four NSCLC cells. Two cells (H358, A549) carried KRAS mutation only, and the other two (H23, H157) harbored comutation of KRAS/PTEN. H358 cells with KRAS mutation only were sensitive to MEK inhibition. However, the other KRAS mutant A549 cells were resistant to MEK inhibition. Previously, we have shown that dual inhibition of EGFR and MEK signaling shows a synergistic effect on KRAS mutant gastric cancer cells by suppressing compensatory activation of AKT. Here we also observed that this combination was effective in KRAS mutant A549 cells. However, the combination was ineffective in H23 and 157 cells with comutation of KRAS/PTEN. Compared to KRAS mutant/PTEN wild-type cells, signal transducer and activator of transcription 3 (STAT3) was significantly activated following MEK inhibition in KRAS/PTEN comutant cells. Combined STAT3 inhibition by a JAK2 inhibitor or gene knockdown with MEK inhibition blocked STAT3 activation, synergistically suppressed cell growth, and induced apoptosis in comutant cells. Taken together, our study provides molecular insights that help explain the heterogeneous response to MEK inhibition in KRAS mutant lung cancers, and presents a rationale for the clinical investigation of combination of MEK and EGFR inhibitor or MEK and JAK2 inhibitor depending on PTEN status.

    PubMed IF 3.5 혈액종양내과
23. 432010

    제1저자 이승표 · 교신저자 김효수

    Lee SP, Kim SY, Park KW, Shin DH, Kang HJ, Koo BK, Suh JW, Cho YS, Yeon TJ, Chae IH, Choi DJ, Kim HS

    Long-term clinical outcome of chronic total occlusive lesions treated with drug-eluting stents: comparison of sirolimus-eluting and paclitaxel-eluting stents.

    Circ J. 2010;74(4):693-700.

    Abstract

    BACKGROUND There are few studies comparing the efficacy of different drug-eluting stents and their long-term clinical outcomes in percutaneous coronary intervention (PCI) of chronic total occlusive (CTO) lesions.

    METHODS AND RESULTS To compare the efficacy of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) for CTO, and to identify predictors of outcome after PCI, 200 patients with at least 1 successfully revascularized CTO were enrolled into either a SES (n=132) or PES (n=71) group. At 6-9-month angiographic follow-up, SES was superior to PES (late loss 0.27+/-0.60 vs 0.53+/-0.62 mm, P=0.04). During mean follow-up of 2 years, the SES group had a significantly lower cumulative target vessel failure (TVF) rate than the PES group (14.9% vs 28.4%, P=0.01), as a consequence of lower target vessel revascularization (9.7% vs 23.9%, P=0.01) and also a partially lower rate of myocardial infarction (MI: 3.1% vs 7.6%, P=0.04). SES was also superior to PES in both early (<or=9 months) and late (>9 months) TVF (P=0.02 for log-rank test, respectively). Predictors for TVF were use of PES (hazard ratio (HR) 3.81, P<0.01), previous history of MI (HR 4.06, P<0.01), diabetes (HR 2.07, P=0.04) and chronic kidney disease (CKD; HR 3.56, P=0.05).

    CONCLUSIONS CTO lesions treated with SES showed better angiographic and long-term clinical outcomes than those treated with PES. Factors such as stent type, infarct-related CTO, diabetes and CKD affect the outcome of CTO intervention.

    PubMed IF 5.8 순환기내과
24. 422010

    제1저자 한승석 · 교신저자 김연수

    Han SS, Sun HK, Lee JP, Ha JW, Kim SJ, Kim YS

    Outcome of renal allograft in patients with Henoch-Schönlein nephritis: single-center experience and systematic review.

    Transplantation. 2010;89(6):721-6.

    Abstract

    BACKGROUND Henoch-Schönlein nephritis (HSN) is a rare condition resulting in end-stage renal disease. Therefore, graft outcomes and recurrence rates after transplantation are not well studied. Also, the effect of donor type on graft outcome has not been evaluated thoroughly.

    METHODS The graft outcome and recurrence rate in 20 kidney recipients with HSN were compared with age-, sex-, and donor source-matched controls (control A, primary immunoglobulin A nephropathy; control B, other causes; 40 recipients per group). To assess the effect of donor type, we pooled our data with two previous cohort studies where donor type had been described in detail.

    RESULTS Overall graft survival rates were 87.7% at 10 years. The overall recurrence rate of HSN was 15.4% over 10 years. Graft survival and recurrence rates in the HSN group were similar to those of control A and control B. The pooled data showed a 29.4% incidence rate for recurrent HSN. Living related donor transplantation showed a trend of higher recurrence compared with recipients with nonrelated grafts, although it was marginally significant (P=0.059). However, the graft survival rate in related-donor recipients was not inferior to that in the unrelated-donor recipients.

    CONCLUSIONS Long-term graft survival and recurrence rates in kidney recipients with HSN were comparable to those of recipients with primary immunoglobulin A nephropathy. The type of donor did not significantly affect long-term graft survival.

    PubMed IF 4.9 신장내과
25. 412010

    제1저자 한세원 · 교신저자 김태유

    Han SW, Oh DY, Im SA, Park SR, Lee KW, Song HS, Lee NS, Lee KH, Choi IS, Lee MH, Kim MA, Kim WH, Bang YJ, Kim TY

    Epidermal growth factor receptor intron 1 CA dinucleotide repeat polymorphism and survival of advanced gastric cancer patients treated with cetuximab plus modified FOLFOX6.

    Cancer Sci. 2010;101(3):793-9.

    Abstract

    Cetuximab is a monoclonal antibody targeting epidermal growth factor receptor (EGFR). The present study investigated the association between germline genetic polymorphisms and the treatment outcome of cetuximab plus modified leucovovin, fluorouracil, and oxaliplatin (FOLFOX)6 chemotherapy in advanced gastric cancer (AGC). DNA from peripheral blood mononuclear cells of 38 patients enrolled in a phase II study of cetuximab plus modified FOLFOX6 were analyzed for 16 polymorphisms in eight genes (EGFR, epidermal growth factor, transforming growth factor-alpha (TGFA), thymidylate synthase, excision repair cross-complementation group 1, Xeroderma pigmentosum group D, and fragment c gamma receptors (FCGR)2A and 3A). The EGFR intron 1 CA repeat polymorphism was associated with survival. Twenty-one patients had low repeats (sum of both alleles <or=37), and 17 patients had high repeats (sum >or=38). Patients with low CA repeats had longer progression-free survival (adjusted hazard ratio [HR] 0.42 [95% confidence interval [CI] 0.19-0.96], P = 0.040) and overall survival (adjusted HR 0.40 [95% CI 0.16-0.99], P = 0.048) compared with patients with high CA repeats. In addition, the tumor EGFR expression was higher in patients with a lower number of CA repeats. The association between the CA repeat status and survival was not found in a separate cohort of AGC patients (n = 68) treated only with modified FOLFOX6. These results suggest that the EGFR intron 1 CA repeat polymorphism could be a useful, predictive biomarker of cetuximab efficacy in AGC and merits further investigation in randomized studies.

    PubMed IF 4.9 혈액종양내과
26. 402010

    제1저자 박경우,김치훈 · 교신저자 김효수

    Park KW, Kim CH, Lee HY, Kang HJ, Koo BK, Oh BH, Park YB, Kim HS

    Does "late catch-up" exist in drug-eluting stents: insights from a serial quantitative coronary angiography analysis of sirolimus versus paclitaxel-eluting stents.

    Am Heart J. 2010;159(3):446-453.e3.

    Abstract

    BACKGROUND Recent studies have suggested the possibility of late catch-up after drug-eluting stent implantation. There are limited data on whether late catch-up exists in sirolimus-eluting stents (SESs) and paclitaxel-eluting stents (PESs).

    METHODS Consecutive patients were routinely recommended 2 serial angiographic follow-ups (at 6-9 and 18-24 months post-percutaneous coronary intervention). A serial quantitative coronary angiographic analysis was performed in lesions not receiving target lesion revascularization at first follow-up. Early luminal loss (LL) was defined as the difference in minimal luminal diameter between the first angiographic follow-up and immediate post-percutaneous coronary intervention, and delayed LL was defined as the difference in minimal luminal diameter between the second and first angiographic follow-up.

    RESULTS Four hundred twelve lesions in the main cohort (PES 128, SES 284) and 47 lesions in the secondary hybrid cohort (PES 23, SES 24), which received serial angiographic follow-ups without target lesion revascularization, were included. In the main cohort, early LL was higher in PES compared with SES (0.56 vs 0.20 mm, P < .01), whereas delayed LL occurring after the first angiographic follow-up was higher in SES (0.10 vs 0.28 mm, P < .01), suggesting more prominent late catch-up in SES. Early LL showed better correlation with total LL (correlation coefficient 0.82 vs 0.30) in PES, whereas delayed LL showed better correlation with total LL (correlation coefficient 0.42 vs 0.91) in SES. Such observations were reproducible in the hybrid cohort, where both SES and PES were implanted at index procedure.

    CONCLUSION Late catch-up occurs in both PES and SES with greater delayed late loss in SES. Our data suggest that the process of neointima formation after SES and PES implantation may follow a slightly different timeline.

    PubMed IF 3.4 순환기내과
27. 392010

    제1저자 강해연 · 교신저자 김상균

    Kang HY, Kim SG, Kim JS, Jung HC, Song IS

    Clinical outcomes of endoscopic submucosal dissection for undifferentiated early gastric cancer.

    Surg Endosc. 2010;24(3):509-16.

    Abstract

    BACKGROUND Early gastric cancer (EGC) with undifferentiated histology has not been generally accepted as an indication for endoscopic treatment. This study was designed to evaluate the outcomes and clinicopathological factors associated with the complete resection of undifferentiated EGC using endoscopic submucosal dissection (ESD).

    METHODS A retrospective analysis of prospectively collected data was performed on consecutive patients who underwent ESD. Among the 456 EGCs treated using ESD at the Seoul National University Hospital, Seoul, Korea, between April 2005 and June 2008, 60 lesions (13.2%) were diagnosed as undifferentiated gastric cancer (poorly differentiated adenocarcinoma or signet ring cell carcinoma).

    RESULTS En bloc resection was performed in all lesions without significant complications. The size discrepancy between the pretreatment endoscopy and the resected specimen was significantly higher in undifferentiated EGCs than differentiated EGCs (p = 0.002). The complete resection rate was significantly lower for undifferentiated EGC (55%) cases than differentiated EGC cases (84.1%; p < 0.001). Independent risk factors for incomplete resection of undifferentiated EGC included tumor size >20 mm, submucosal invasion, and presence of ulceration. During a mean observation time of 16 months, no recurrence developed in any of the patients with undifferentiated EGCs thought to be completely resected by ESD.

    CONCLUSIONS ESD might be considered an alternative treatment modality in carefully selected cases of undifferentiated EGC.

    PubMed IF 3.3 소화기내과
28. 382010

    제1저자 오진영 · 교신저자 이춘택

    Oh JY, Park MY, Kim DR, Lee JH, Shim SH, Chung JH, Yoon HI, Lee JH, Sung MW, Kim YS, Lee CT

    Combination gene therapy of lung cancer with conditionally replicating adenovirus and adenovirus-herpes simplex virus thymidine kinase.

    Int J Mol Med. 2010;25(3):369-76.

    Abstract

    A major obstacle to the success of gene therapy strategies that directly target cancer cells is the low gene transfer rate. To address this problem, we had previously proposed a combination adenoviral gene therapy containing a conditionally replicating adenovirus (CRAD) expressing mutant E1 (Delta24RGD), and a replication-defective E1-deleted adenovirus to enhance the efficiency of gene transfer. Suicide/pro-drug gene therapy has an important additional benefit to the therapy of cancer. This relates to the transfer and expression of non-mammalian genes encoding enzymes that convert non-toxic pro-drugs into cellular toxins. We investigated the interaction between CRAD (Delta24RGD) and a replication-defective E1-deleted adenovirus (ad-HSTK) containing a suicide gene (HSTK: herpes simplex virus thymidine kinase gene) with respect to therapeutic gene production and tumor cell killing efficacy. Combined transduction of CRAD and ad-HSTK increased the transduction efficiency of HSTK and increased its sensitivity to ganciclovir (GCV) more efficiently than ad-HSTK alone. Transfer of medium of CRAD and ad-HSTK co-transduced cells induced the transfer of HSTK (media transferable bystander effect), and enhanced its sensitivity to GCV. In an animal tumor model, combined intratumoral injection of CRAD and ad-HSTK followed by GCV administration induced prolonged expression of HSTK and stronger growth suppression of established lung cancer xenografts than single injections. These data demonstrate that the selective replication of ad-HSTK due to the presence of mutant E1, produced by a Delta24RGD and HSTK/GCV suicide gene system, resulted in a striking improvement in anti-tumor effects in vitro and in vivo.

    PubMed IF 8.5 호흡기내과
29. 372010

    제1저자 황성욱 · 교신저자 이동호

    Hwang SW, Lee DH, Lee SH, Park YS, Hwang JH, Kim JW, Jung SH, Kim NY, Kim YH, Lee KH, Kim HH, Park DJ, Lee HS, Jung HC, Song IS

    Preoperative staging of gastric cancer by endoscopic ultrasonography and multidetector-row computed tomography.

    J Gastroenterol Hepatol. 2010;25(3):512-8.

    Abstract

    BACKGROUND AND AIM The aim of this study was to determine the accuracy of endoscopic ultrasonography (EUS) and multidetector-row computed tomography (MDCT) for the locoregional staging of gastric cancer. EUS and computed tomography (CT) are valuable tools for the preoperative evaluation of gastric cancer. With the introduction of new therapeutic options and the recent improvements in CT technology, further evaluation of the diagnostic accuracy of EUS and MDCT is needed.

    METHODS In total, 277 patients who underwent EUS and MDCT, followed by gastrectomy or endoscopic resection at Bundang Hospital, Seoul National University, from July 2006 to April 2008, were analyzed. The results from the preoperative EUS and MDCT were compared to the postoperative pathological findings.

    RESULTS Among the 277 patients, the overall accuracy of EUS and MDCT for T staging was 74.7% and 76.9%, respectively. Among the 141 patients with visualized primary lesions on MDCT, the overall accuracy of EUS and MDCT for T staging was 61.7% and 63.8%, respectively. The overall accuracy for N staging was 66% and 62.8%, respectively. The performance of EUS and MDCT for large lesions and lesions at the cardia and angle had significantly lower accuracy than that of other groups. For EUS, the early gastric cancer lesions with ulcerative changes had significantly lower accuracy than those without ulcerative changes.

    CONCLUSIONS For the preoperative assessment of individual T and N staging in patients with gastric cancer, the accuracy of MDCT was close to that of EUS. Both EUS and MDCT are useful complementary modalities for the locoregional staging of gastric cancer.

    PubMed IF 3.5 소화기내과
30. 362010

    제1저자 김형관 · 교신저자 김형관

    Kim HK, Chang SA, Sohn DW, Kim DH, Kim YJ, Oh BH, Park YB

    Persistent regional diastolic dysfunction after myocardial ischemia and the effect of statin treatment: assessment with two-dimensional radial strain rate.

    Echocardiography. 2010;27(3):244-52.

    Abstract

    BACKGROUND Persistence of regional diastolic dysfunction after ischemic insult remains debatable. With speckle tracking echocardiography (STE), we sought to (1) prove the persistence of regional diastolic dysfunction, (2) assess the feasibility of applying persistent regional diastolic dysfunction to differentiating ischemic and nonischemic chest pain, and finally (3) examine statin effects on postischemic regional diastolic dysfunction.

    METHODS Nineteen patients with variant angina (VA) and 12 normal subjects were enrolled. Comprehensive echocardiographic examinations were performed before and 1 day after coronary angiography (CAG) with ergonovine provocation. Radial systolic (rSRsys) and diastolic (rSRdia) strain rates were obtained and averaged using standard segmentation models corresponding to the three major coronary territories assigned.

    RESULTS No significant changes in rSRsys and rSRdia values were observed for controls and in rSRsys for VA. However, rSRdia for VA demonstrated a weak, but significant, decrease from -2.25 +/- 0.71/sec to -2.04 +/- 0.71/sec (P = 0.003) 1 day after CAG. However, because of the wide overlap between rSRdia values in normal and ischemic segments for VA patients, predictability of remote ischemia based solely on the rSRdia was limited. Subgroup analysis according to statin prescription showed that statin administration contributed to the elimination of rSRdia reduction (-2.28 +/- 0.84/sec on pre-CAG vs. -2.29 +/- 0.77/sec on post-CAG, P = 0.72 for patients without statin premedication; -2.23 +/- 0.64/sec for pre-CAG vs. -1.88 +/- 0.65/sec for post-CAG, P = 0.002 for those without). Expectedly, rSRsys values showed no significant changes in all situations.

    CONCLUSIONS The presence and sustained nature of regional diastolic dysfunction can be demonstrated with STE. Statin minimized the persistence of regional diastolic dysfunction after an acute ischemia. Although the clinical usefulness of rSRdia by STE appears to be limited, its clinical utility requires further consideration, given the brevity of the ischemia provoked during CAG with ergonovine and the protracted regional diastolic dysfunction.

    PubMed IF 1.8 순환기내과

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