SCI 발표논문

2009년 146편

1162009

제1저자 Jizhe Jin · 교신저자 김연수

, , , , , ,
Fragile maintenance of allograft tolerance induced by lymphocyte sequestration and co-stimulation blockade.
Transpl Immunol. 2009;21(4):221-7.

Abstract
The induction of long-term graft survival has been a goal for the last decade. Nevertheless, the issues of stable maintenance of allograft have not yet been evaluated thoroughly. Here, we studied new approaches for induction of tolerance by lymphocyte sequestration (FTY720) and co-stimulatory blockade (MR1) in skin graft model (DBA/2 to BALB/c), thus evaluating the mechanisms incorporated into the maintenance of allograft in proper function. FTY720+MR1 treatment significantly prolonged graft survival than single agent treatment did, and induced long-term graft survival in 60% of recipients expressing the up-regulation of IL-4 and FoxP3. To assess the stability of graft maintenance, we performed the second transplantation on recipients that had shown long-term graft survival. While recipients accepted the second graft from the same strain of first donor, the recipients not only rejected the third-party skin (C57BL/6) promptly but also rejected the first graft soon after the third-party skin was transplanted. The expression patterns of IL-4 and FoxP3 were changed according to the strains of second graft in lymph nodes and in the first graft. T(reg) cells from tolerant recipients effectively suppressed allo-antigen driven T cell proliferation, but T(reg) cells from recipients primed with third-party antigen had significantly hampered suppressive capacity against previously tolerant antigens. Our data indicate that the combination treatment provides effective tool for the induction of long-term graft survival, and the maintenance of allograft in proper function is an actively regulated process.
PubMed IF 1.6 신장내과
1152009

제1저자 차란희 · 교신저자 김연수

, , , , , ,
Genetic interactions between the donor and the recipient for susceptibility to acute rejection in kidney transplantation: polymorphisms of CCR5.
Nephrol Dial Transplant. 2009;24(9):2919-25.

Abstract
BACKGROUND Acute rejection (AR) contributes to the development of chronic allograft nephropathy that is the major cause of graft failure. We analyzed the 59029G>A polymorphism and an internal 32 bp deletion (CCR5 32) of CCR chemokine receptor 5 (CCR5) Delta and tried to prove the hypothesis that genetic interactions between the donor and the recipient influence the development of AR.
METHODS We detected genetic polymorphisms by the TaqMan(R) method and by sizing PCR amplicons (n = 486). The primary outcomes were early acute rejection (EAR) and repeated early acute rejection (RR). We defined EAR as the occurrence of a biopsy-proven AR within 3 months after transplantation.
RESULTS The development of EAR was dependent on the number of A alleles in recipients and showed a dose-response relationship (P = 0.002). When we combined the number of A alleles in both donor and recipient, episodes of EAR and RR were more prevalent as the allelic number increased (A allelic number 0 & 1, 2 versus 3 & 4, P = 0.048; 0 & 1 versus 3 & 4, P = 0.006). Statistical significance was preserved after multivariate analysis of sex, HLA mismatch and type of donor with the recipient's age as the continuous term. Also, graft survival was different according to the presence of the A allele, i.e. recipients carrying A allele (+) grafts showed poor graft survival (P = 0.008 by a log-rank test). Again, the number of A alleles affected graft survival as the recipients who carried more A alleles had poor graft survival (A allele number 0 & 1 versus 2 versus 3 & 4, P = 0.011; 0 & 1 versus 3 & 4, P = 0.08; 0 & 1 versus 2, P = 0.002; by a log-rank test). All of the participants were wild-type homozygotes for CCR5Delta32.
CONCLUSIONS The A allele of CCR5 59029G>A was a risk factor for EAR and RR. As the number of A alleles increased, episodes of EAR were more frequently observed.
PubMed IF 8.3 신장내과
1142009

제1저자 김세중 · 교신저자 오국환

, , , , , ,
Benefits of biocompatible PD fluid for preservation of residual renal function in incident CAPD patients: a 1-year study.
Nephrol Dial Transplant. 2009;24(9):2899-908.

Abstract
BACKGROUND In vitro studies of peritoneal dialysis (PD) solutions demonstrated that a biocompatible fluid with neutral-pH and low glucose degradation products (LF) has better biocompatibility than a conventional acidic lactate-buffered fluid (CF). However, few clinical trials have investigated the effects of the biocompatible solution on residual renal function (RRF). We performed a prospective, randomized trial with patients starting continuous ambulatory peritoneal dialysis (CAPD).
METHODS Ninety-one incident patients started CAPD for 12-month treatment with either LF (Balance, Fresenius, n = 48) or CF (CAPD/DPCA, Fresenius, n = 43). RRF, peritoneal solute transport rate and solute clearance were measured every 6 months.
RESULTS LF had a significant effect on the change of glomerular filtration rate (GFR) (P = 0.048 by the mixed model). In per-protocol analysis, GFR in the LF group did not decrease over a 12-month period, while GFR in the control group significantly decreased (0.13 +/- 33.4 L/ week/1.73 m(2) for LF versus -13.6 +/- 19.4 L/week/1.73 m(2) for CF, P = 0.049). Subgroup analysis for patients with initial GFR of 2 mL/min/1.73 m(2) or above showed a significantly higher GFR for the LF group over the 12-month period. At Month 13, serum total CO(2) levels were higher and serum albumin levels were lower in the LF group. No differences between the two groups were observed for the C-reactive protein. Over the 12-month period, effluent cancer antigen-125 levels significantly increased in the LF group, compared with those of the CF group, while effluent interleukin-6 levels were not different between the two groups.
CONCLUSION Our study suggests that LF may better preserve RRF over the 12-month treatment period in incident CAPD patients.
PubMed IF 8.3 신장내과
1132009

제1저자 장성아 · 교신저자 김용진

, , , , , , , ,
Effect of rosuvastatin on cardiac remodeling, function, and progression to heart failure in hypertensive heart with established left ventricular hypertrophy.
Hypertension. 2009;54(3):591-7.

Abstract
Hypertensive patients with left ventricular hypertrophy (LVH) are the most common high-risk group to develop heart failure with preserved ejection fraction. Recent reports have noted the favorable effect of statins on LVH. We evaluated the effect of rosuvastatin on cardiac remodeling, function, and progression to heart failure in a hypertensive rat model with established LVH. Dahl salt-sensitive rats were fed a high-salt diet until 13 weeks of age. After LVH was confirmed by echocardiography, rats were randomly assigned to control and statin treatment (n=18 each group). The statin-treated group was treated with rosuvastatin until 21 weeks of ages. Serial echocardiography, blood pressure monitoring, and miniaturized conductance catheter hemodynamic monitoring were performed at 21 weeks. Echocardiographic parameters were not significantly different between the groups. On hemodynamic monitoring, systolic performance parameters were similar between the groups, whereas end diastolic pressure-volume relationships were lower in the statin-treated group (0.014+/-0.008 versus 0.008+/-0.004 mm Hg/muL, P<0.05), suggesting improvement in myocardial stiffness. Pathological analysis showed attenuation of perivascular and interstitial fibrosis in the statin-treated group (P<0.02). Rosuvastatin therapy did not alleviate LVH in hypertensive rats with established LVH, but it attenuated myocardial fibrosis and LV stiffness. It seems that rosuvastatin has limited therapeutic value when used to prevent progression from LVH to heart failure in hypertensive hearts.
PubMed IF 9.8 순환기내과
1122009

제1저자 이근욱 · 교신저자 허대석

, , , , , , , , , , , , , ,
Risk factors for poor treatment outcome and central nervous system relapse in diffuse large B-cell lymphoma with bone marrow involvement.
Ann Hematol. 2009;88(9):829-38.

Abstract
Although several studies have described the prognostic implication of bone marrow (BM) involvement (BMI) in lymphoma, studies focused on BM-involved diffuse large B-cell lymphoma (DLBCL) are very rare and small-sized. This study was performed to examine the prognostic impact of morphologic findings of BMI by lymphoma and risk factors for central nervous system (CNS) relapse in BM-involved DLBCL. Between 1993 and 2005, 675 patients were diagnosed with DLBCL, and 88 patients who had BMI at initial diagnosis were eligible for this study. The median overall survival (OS) and failure-free survival (FFS) of 88 patients were 36.6 and 20.1 months, respectively. When three variables from BM morphologic findings (the pattern of BM infiltration, extent of BMI by lymphoma, and percentage of large cells in the infiltrate) were simultaneously included into multivariate model, the increased extent of BMI by lymphoma (> or =10%) in BM area was the only negative prognostic factor, independent of the International Prognostic Index (IPI). Patients with both lower IPI scores and less extent of BMI showed an excellent prognosis with chemotherapy alone (5-year OS and FFS rates, 80% and 69%). However, morphologic BM features were not independent predictive factors for CNS recurrences. An increased lactate dehydrogenase (LDH) level at initial diagnosis was the only independent predictive factor for CNS relapse. Further efforts should be directed toward finding optimal treatment modalities based on the IPI and the extent of BMI by lymphoma. CNS prophylaxis may be considered only in patients with initial elevated LDH levels.
PubMed IF 2.3 혈액종양내과
1112009

제1저자 강은하 · 교신저자 송영욱

, , , , ,
Downregulation of heat shock protein 70 protects rheumatoid arthritis fibroblast-like synoviocytes from nitric oxide-induced apoptosis.
Arthritis Res Ther. 2009;11(4):R130.

Abstract
INTRODUCTION Heat shock protein 70 (Hsp70) is a well-known anti-apoptotic protein that blocks multiple steps in the stress-induced apoptotic pathway. Enhanced Hsp70 expression has previously been demonstrated in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs). The authors investigated the role of Hsp70 in the survival of RA FLSs in a sodium nitroprusside (SNP)-treated environment.
METHODS Targeted knock-down of Hsp70 was performed by RNA interference in RA FLSs at passage 3-7. After SNP treatment, the morphological features of apoptosis were observed by phase-contrast microscopy. Cell survival was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays and by flow cytometric analysis after propidium iodide (PI) staining. Bcl-2 expression and signaling pathways (Akt, extracellular signal-regulated kinase, p38, c-Jun N-terminal kinase) were examined with or without Hsp70 downregulation.
RESULTS Hsp70 downregulation in RA FLSs, induced by small interfering RNA (siRNA), was confirmed by reverse transcriptase-polymerase chain reaction and Western blotting. When treated with SNP, Hsp70 downregulated cells showed markedly less cell blebbing, cytoplasmic condensation, and nuclear shrinkage than non-downregulated control cells. Furthermore, Hsp70 downregulated cells were found to survive better than control cells in MTT assays (mean of absorbance ratio, 4.39 in target cells versus 1.00 in control siRNA-treated cells versus 1.09 in lipofectamine-treated cells, P = 0.001) and according to PI staining results (mean M1 ratio, 0.21 in target cells versus 1.00 in control siRNA-treated cells versus 1.03 in lipofectamine-treated cells, P = 0.001). Bcl-2 expression and Akt phosphorylation were higher in Hsp70 downregulated RA FLSs than in control cells. When cells were treated with LY294002, a potent phosphoinositide 3-kinase inhibitor, Akt phosphorylation and Bcl-2 levels were reduced and Hsp70 downregulation no longer had a cytoprotective effect.
CONCLUSIONS Knock-down of Hsp70 protects RA FLSs from nitric oxide-induced apoptosis by activating the Akt signaling pathway. These results suggest that Hsp70 has a pro-apoptotic role in RA FLSs.
PubMed IF 5.4 류마티스내과
1102009

제1저자 정혜승 · 교신저자 김광원

, , , , , ,
Enhancement of beta-cell regeneration by islet transplantation after partial pancreatectomy in mice.
Transplantation. 2009;88(3):354-9.

Abstract
BACKGROUND Pancreatic beta cells are known to regenerate, especially when insulin requirements are increased. Islet transplantation (ITx) is one strategy for insulin replacement in patients with diabetes. ITx can provide not only insulin in a physiological manner but also can exert additional effects such as beta-cell regeneration. This study examined the effects of ITx on endogenous beta-cell mass in mice.
METHODS Male Balb/c mice were 70% pancreatectomized and transplanted with syngeneic islets, then compared with pancreatectomized mice with or without insulin treatment. Blood glucose levels and weight were evaluated for 10 days, with remnant pancreas obtained for evaluation of beta-cell mass and turnover.
RESULTS Hyperglycemia and weight loss were induced after pancreatectomy (Px). After ITx or insulin treatment, blood glucose levels recovered to normal, and body weight started to increase. At 10 days after Px, fasting serum insulin levels, beta-cell mass, and insulin content in the remnant pancreas were higher in the ITx group than they were in the Px group. Insulin treatment after Px also increased beta-cell mass, but did not increase pancreatic insulin content compared with those in the Px group. The enhanced beta-cell mass and insulin content in the remnant pancreas of the ITx group resulted from increased beta-cell proliferation/neogenesis and from prevention of beta-cell apoptosis.
CONCLUSIONS These findings suggest that ITx after partial Px in mice enhances endogenous beta-cell regeneration and survival, rendering beta-cell mass increased and glucose homeostasis improved.
PubMed IF 4.9 내분비대사내과
1092009

제1저자 조구영 · 교신저자 조구영

, , , , ,
Global 2-dimensional strain as a new prognosticator in patients with heart failure.
J Am Coll Cardiol. 2009;54(7):618-24.

Abstract
OBJECTIVES We sought to evaluate whether global 2-dimensional (2D) strain offers additional benefit over left ventricular ejection fraction (LVEF) to predict clinical events in heart failure.
BACKGROUND Although 2D strain based on speckle tracking has been proposed as a simple and reproducible tool to detect systolic dysfunction, the relationship of 2D strain and prognosis has not been studied.
METHODS Two hundred one patients (age 63 +/- 11 years, 34% female, LVEF 34 +/- 13%) hospitalized for acute heart failure underwent clinical evaluation and conventional and tissue Doppler echocardiography. Using dedicated software, we measured the global longitudinal strain (GLS) in apical 4- and 2-chamber views and the global circumferential strain (GCS) in a parasternal short-axis view. Cardiac events were defined as readmission for heart failure or cardiac death.
RESULTS There were 23.4% clinical events during 39 +/- 17 months of follow-up. In univariate analysis, age, left atrial volume, left ventricular volume, LVEF, ratio of early transmitral flow to early diastolic annular velocity (E/e'), and both GLS and GCS were predictive of cardiac events. In multivariate Cox models, age (hazard ratio [HR]: 1.06, 95% confidence interval [CI]: 1.01 to 1.10, p = 0.017) and GCS (HR: 1.15, 95% CI: 1.04 to 1.28; p = 0.006) were independently associated with cardiac events. By Cox proportional hazards model, the addition of GCS markedly improved the prognostic utility of a model containing ejection fraction, E/e', and GLS.
CONCLUSIONS GCS is a powerful predictor of cardiac events and appears to be a better parameter than ejection fraction in patients with acute heart failure.
PubMed IF 22.3 순환기내과
1082009

제1저자 최수연 · 교신저자 김동희

, , , , , , , , , , , , , , ,
The relation between non-alcoholic fatty liver disease and the risk of coronary heart disease in Koreans.
Am J Gastroenterol. 2009;104(8):1953-60.

Abstract
OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is known to be related to factors that predict the development of coronary heart disease (CHD), such as dyslipidemia, central obesity, and metabolic syndrome (MS). The aim of this study was to determine whether individuals with NAFLD have an elevated risk of CHD, as estimated using the Framingham risk score (FRS).
METHODS A total of 21,130 individuals who underwent a voluntary general health examination were recruited. NAFLD was diagnosed among these individuals on the basis of typical sonographic findings and a level of alcohol consumption of <20 g/day. Of the 21,130 individuals, 3,780 were excluded because they had known causes of liver disease (1,690 were alcoholics, 975 had hepatitis B virus, 242 had hepatitis C virus, 91 had other hepatitis history, and 593 were taking medication known to produce fatty liver) or a history of heart disease (189).
RESULTS NAFLD was diagnosed in 5,769 of the 17,350 individuals (33.3%). The 11,581 normal individuals constituted the control group. The 5,769 individuals with NAFLD were split into two groups on the basis of ultrasonographic findings, that is, into a mild NAFLD group (n=3,278) and a moderate-severe NAFLD group (n=2,491). Individuals with NAFLD had an elevated risk of CHD, as estimated using FRS. Multivariable regression analysis, adjusted for confounding factors, showed a strong association between a higher FRS and NAFLD.
CONCLUSIONS Individuals with ultrasonographically detected NAFLD have an elevated 10-year risk of developing CHD as estimated using FRS. Furthermore, NAFLD was found to be independently related to the risk of developing CHD, regardless of classical risk factors and other components of MS.
PubMed IF 7.6 소화기내과
1072009

제1저자 이정옥 · 교신저자 오도연

, , , , , ,
Combination chemotherapy with capecitabine and cisplatin for patients with metastatic hepatocellular carcinoma.
Ann Oncol. 2009;20(8):1402-7.

Abstract
BACKGROUND We evaluated the efficacy and toxicity of combination chemotherapy with capecitabine and cisplatin (XP) in patients with metastatic hepatocellular carcinoma (HCC).
PATIENTS AND METHODS From September 2003 to July 2007, we enrolled patients with HCC who had more than one measurable extrahepatic metastatic lesion. Patients received oral capecitabine (2000 mg/m(2)/day) with a schedule of 2 weeks on and 1 week off and cisplatin (60 mg/m(2)) on the first day of the 3-week cycle.
RESULTS The study cohort consisted of 32 patients with a median age of 53 years. Overall response rate was 6.3% and disease control rate was 34.4%. The median time to progression (TTP) was 2.0 months [95% confidence interval (CI) 1.5-2.4] and the median overall survival (OS) time was 12.2 months (95% CI 6.5-17.8). The grade 3/4 hematologic toxic effects included thrombocytopenia (7.6%), neutropenia (4.3%) and anemia (2.1%). The grade 3/4 non-hematologic toxic effects included elevated hepatic aminotransferase (12.9%), jaundice (3.2%), mucositis (3.2%) and nausea (3.2%). There was no treatment-related mortality.
CONCLUSIONS Based on the observed response rate and TTP, XP combination chemotherapy showed modest antitumor efficacy in patients with metastatic HCC as systemic first-line treatment. However, XP combination chemotherapy showed tolerable toxicity and demonstrated favorable OS time.
PubMed IF 80.4 혈액종양내과
1062009

제1저자 고영일 · 교신저자 이세훈

, , , , , , , , , , , ,
Class III beta-tubulin, but not ERCC1, is a strong predictive and prognostic marker in locally advanced head and neck squamous cell carcinoma.
Ann Oncol. 2009;20(8):1414-9.

Abstract
BACKGROUND Recent researches revealed that class III beta-tubulin (TUBB3) is a prognostic marker in various tumors and role of TUBB3 in head and neck squamous cell carcinoma (HNSCC) is not defined yet. We analyzed the significance of TUBB3 expression along with p53 and ERCC1 in locally advanced HNSCC patients receiving cisplatin-based induction chemotherapy.
MATERIALS AND METHODS Retrospective review of medical records at Seoul National University Hospital between 1998 and 2007 was carried out. Immunohistochemical stain of TUBB3, p53, and ERCC1 was done in paraffin-embedded tumor tissue. We assessed response to treatment, progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS).
RESULTS Eighty-five patients with oropharyngeal, hypopharyngeal, and laryngeal cancers received induction chemotherapy with 5-fluorouracil (5-FU) and cisplatin (n = 55), or 5-FU, cisplatin, and docetaxel (Taxotere) (n = 30). Eighty-three received definitive treatment after induction chemotherapy, where 62 received radiotherapy and 21 received surgery. TUBB3-positive patients showed lower response rate than TUBB3-negative patients (69% versus 88%, P = 0.039). Shorter median PFS was observed in TUBB3-positive group (12 versus 47 months, P = 0.001). Shorter median OS was observed in TUBB-positive group not reaching statistical significance (30 versus 59 months, P = 0.072). TUBB3 status significantly influenced CSS (35 months versus not reached, P = 0.017). Positive p53 status was related to poorer OS and CSS. ERCC1 showed no influence on chemotherapy response, PFS, OS, and CSS.
CONCLUSION TUBB3 is a predictive and prognostic marker along with well-known p53 in HNSCC patients receiving cisplatin-based induction chemotherapy. Clinical impact of ERCC1 is not evident in this setting.
PubMed IF 80.4 혈액종양내과
1052009

제1저자 안화영 · 교신저자 조영민

, , , , , , ,
Predictive factors associated with the reversibility of post-transplantation diabetes mellitus following liver transplantation.
J Korean Med Sci. 2009;24(4):567-70.

Abstract
Post-transplantation diabetes mellitus (PTDM) is reversible in a considerable number of patients. We examined the prevalence and predictive factors of transient PTDM following liver transplantation. Forty-two of 74 PTDM patients showed the clinical features of transient PTDM. Compared with the persistent PTDM patients, they were characterized by younger age at the time of transplantation (49+/-7 vs. 53+/-8 yr, P<0.05), longer time before the development of PTDM (44+/-59 vs. 13+/-20 days, P<0.05), lower rate of hepatitis c virus seropositivity (0.0 vs. 9.4%, P<0.05), and use of mycophenolate mofetil (59.5 vs. 28.1%, P<0.05). Among these risk factors, age at the time of transplantation is the single independent predictive factor associated with the reversibility of PTDM.
PubMed IF 3.2 내분비대사내과
1042009

제1저자 최동현,서정원 · 교신저자 김효수

, , , ,
Assessment of the bioequivalence of brand and biogeneric formulations of abciximab for the treatment of acute coronary syndrome: a prospective, open-label, randomized, controlled study in Korean patients.
Clin Ther. 2009;31(8):1804-11.

Abstract
BACKGROUND Abciximab has been found to reduce major adverse cardiovascular events in patients with acute coronary syndrome (ACS). A previous study reported on the tolerability of biogeneric abciximab in patients with ACS. This formulation has been approved by the Korea Food and Drug Administration and is currently being marketed. Its ex vivo antiplatelet effect, however, has not been compared with that of branded abciximab.
OBJECTIVE The purpose of the present study was to compare ex vivo antiplatelet activity, angiographic outcome, and bleeding complications between biogeneric and branded abciximab.
METHODS This prospective, open-label, randomized, controlled study was conducted in Korea. Patients with ACS who underwent percutaneous coronary intervention (PCI) were randomized to receive biogeneric abciximab or branded abciximab. All patients received intracoronary unfractionated heparin 70 IU/kg and either biogeneric or branded abciximab 0.25 mg/kg IV bolus approximately 10 minutes before undergoing PCI, followed by a 0.125 microg/kg/min 12-hour infusion of the same formulation. The antiplatelet effect of both drugs was assessed at 3 time points (at baseline, and 10 minutes and 24 hours after the end of the bolus infusion) using a validated rapid platelet-function assay.
RESULTS In total, 37 patients (30 men and 7 women; 19 receiving biogeneric abciximab and 18 receiving branded abciximab) were included. Patient demographics did not differ significantly between the 2 groups (16 men [84.2%] and 3 women [15.8%] in the biogeneric group vs 14 men [77.8%] and 4 women [22.2%] in the branded group; mean [SD] age, 65 [11] vs 60 [10] years; weight, 64.6 [8.7] vs 67.9 [10.1] kg, respectively). The bolus and the continuous infusion of the biogeneric and branded formulations achieved similar levels of platelet inhibition, with a mean (SD) inhibition of platelet aggregation >90% at 10 minutes after the end of the bolus infusion (94.7% [8.2%] vs 92.6% [16.9%], respectively; P = NS) and >65% at 24 hours (68.1% [9.8%] vs 70.9% [9.7%]; P = NS) compared with baseline. One thrombolysis in myocardial infarction major bleeding complication (retro-peritoneal hemorrhage) was reported in a patient who received biogeneric abciximab.
CONCLUSION There were no statistically significant differences in the antiplatelet effects of these 2 formulations in this small, selected population of Korean patients with ACS.
PubMed IF 3.7 순환기내과
1032009

제1저자 심기남 · 교신저자 김나영

, , , , , , , , , , , , , , , , , , , , , , , , , ,
Clinical spectrum of reflux esophagitis among 25,536 Koreans who underwent a health check-up: a nationwide multicenter prospective, endoscopy-based study.
J Clin Gastroenterol. 2009;43(7):632-8.

Abstract
BACKGROUND Gastroesophageal reflux is a commonly encountered condition, but detailed data on reflux symptoms in Asian countries are lacking.
GOALS To evaluate the prevalence and to document the clinical spectrum of endoscopic reflux esophagitis (RE).
STUDY A total 25,536 subjects underwent an upper gastrointestinal endoscopic examination as part of a health check, and completed a gastroesophageal reflux questionnaire. Endoscopic findings classified according to the Los Angeles (LA) classification and the data from gastroesophageal reflux questionnaire were analyzed.
RESULTS On the basis of endoscopic findings, 2019 subjects (7.91%) were found to have RE: 5.87% in LA-A; 1.84% in LA-B; 0.18% in LA-C; and 0.02% in LA-D. Heartburn, acid regurgitation, chest pain, hoarseness, globus sensation, cough, and epigastric soreness were found to be associated with RE (P<0.05). Heartburn, acid regurgitation, and epigastric soreness were more frequent in LA-B than in LA-A (P<0.05). Epigastric soreness was most bothersome in LA-A and LA-B, and acid regurgitation was most bothersome in LA-C and LA-D (P<0.01). Heartburn, hoarseness, and globus sensation were more frequent in men with RE, and acid regurgitation was most common in women.
CONCLUSIONS The prevalence of RE was found to be 7.91% in Korea, and the profiles of reflux symptoms were found to depend on grade of RE and sex.
PubMed IF 2.7 소화기내과
1022009

제1저자 장희창 · 교신저자 오명돈

, , , , , , , , , , , , ,
Salvage treatment for persistent methicillin-resistant Staphylococcus aureus bacteremia: efficacy of linezolid with or without carbapenem.
Clin Infect Dis. 2009;49(3):395-401.

Abstract
BACKGROUND Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with high mortality rates, but no treatment strategy has yet been established. We performed this study to evaluate the efficacy of linezolid with or without carbapenem in salvage treatment for persistent MRSA bacteremia.
METHODS All adult patients with persistent MRSA bacteremia for 7 days from January 2006 through March 2008 who were treated at Seoul National University Hospital were studied. The results of linezolid salvage therapy with or without carbapenem were compared with those of salvage therapy with vancomycin plus aminoglycosides or rifampicin.
RESULTS Thirty-five patients with persistent MRSA bacteremia were studied. The early microbiological response (ie, negative results for follow-up blood culture within 72 hours) was significantly higher in the linezolid-based salvage therapy group than the comparison group (75% vs 17%; P =.006). Adding aminoglycosides or rifampicin to vancomycin was not successful in treating any of the patients, whereas linezolid-based therapy gave an 88% salvage success rate P =.001). The S. aureus-related mortality rate was lower for patients treated with a linezolid salvage regimen than for patients continually treated with a vancomycin-based regimen (13% vs 53%; P =.030).
CONCLUSIONS Linezolid-based salvage therapy effectively eradicated S. aureus from the blood for patients with persistent MRSA bacteremia. The salvage success rate was higher for linezolid therapy than for vancomycin-based combination therapy.
PubMed IF 8.3 감염내과
1012009

제1저자 김홍빈 · 교신저자 David C. Hooper

, , , , ,
oqxAB encoding a multidrug efflux pump in human clinical isolates of Enterobacteriaceae.
Antimicrob Agents Chemother. 2009;53(8):3582-4.

Abstract
The genes for multidrug efflux pump OqxAB, which is active on fluoroquinolones, were found in human clinical isolates on a plasmid in Escherichia coli and on the chromosome of Klebsiella pneumoniae. IS26-like sequences flanked the plasmid-mediated oqxAB genes, suggesting that they had been mobilized as part of a composite transposon.
PubMed IF 4.2 감염내과
1002009

제1저자 오국환 · 교신저자 안규리,장인진

, , , , , , , , ,
Pharmacokinetics of intravenous piperacillin administration in patients undergoing on-line hemodiafiltration.
Antimicrob Agents Chemother. 2009;53(8):3266-8.

Abstract
The pharmacokinetic characteristics of piperacillin sodium were studied in five volunteers undergoing on-line hemodiafiltration (HDF). The subjects were given 2 g of piperacillin sodium intravenously over 1 min and placed on on-line HDF for 4 h starting at 60 min after the piperacillin infusion. Noncompartmental models were employed for estimation of the pharmacokinetic parameters, and intradialytic piperacillin clearance was calculated by the recovery method. The mean volume of distribution and the elimination half-life were 0.27 +/- 0.13 liter/kg (mean +/- standard deviation) and 1.1 +/- 0.6 h, respectively. The total body clearance of piperacillin was 0.19 +/- 0.08 liter/h/kg. Piperacillin clearance through on-line HDF was 0.11 +/- 0.06 liter/h/kg. The mean serum piperacillin concentration was 4.0 +/- 1.9 microg/ml at the end of the 4-h on-line HDF session. The concentration of infused piperacillin recovered in the dialysate was 527 +/- 236 mg (26.3% +/- 11.8%). We suggest the replacement of 500 mg of piperacillin after each on-line HDF session.
PubMed IF 4.2 신장내과
992009

제1저자 김원 · 교신저자 윤정환

, , , , , ,
Synergistic anti-tumor efficacy of lovastatin and protein kinase C-beta inhibitor in hepatocellular carcinoma.
Cancer Chemother Pharmacol. 2009;64(3):497-507.

Abstract
PURPOSE Hepatocellular carcinoma (HCC) is characterized by hypervascularity and chemoresistance. Protein kinase C (PKC) participates in cancer progression by enhancing anti-apoptotic signals, angiogenesis, and chemoresistance. Statins have a selective anti-cancer effect due to over-expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR) in cancer cells, but statins may also activate PKC. Thus, we hypothesized that simultaneous treatment with statin and PKC inhibitor might synergistically enhance their anti-tumor efficacies against HCCs.
METHODS Hepatocellular carcinoma cell growth was assessed using MTS assays, apoptotic cell death by DAPI staining, and apoptotic signaling cascades were explored by immunoblotting. An in vivo model of HCC was established in C3H mice intradermally implanted with MH134 cells. Lovastatin and/or a PKC inhibitor (enzastaurin) was subsequently administered. Anti-tumor efficacies were evaluated by measuring tumor volumes and quantifying apoptotic cells and microvessel densities (MVD).
RESULTS Co-treatment with lovastatin and enzastaurin was found to synergistically suppress HCC cell growth in vitro. Lovastatin induced HCC cellular apoptosis by activating mitochondrial apoptotic signals, and although enzastaurin alone did not induce apoptosis, its addition significantly enhanced lovastatin-induced apoptosis. This enhanced apoptosis was attributed to increased caspase-9 activation in these cells. Moreover, tumor growth was significantly suppressed in mice co-treated with lovastatin and enzastaurin, and percentages of TUNEL-positive cells were significantly increased and MVDs were significantly decreased in those mice.
CONCLUSION Combinatorial treatment with statin and PKC inhibitor was found to enhance anti-tumor efficacy in vivo and in vitro. Further studies are warranted to prove anti-tumor efficacy of this potential therapy in human HCCs.
PubMed IF 2.5 소화기내과
982009

제1저자 심성훈 · 교신저자 김동완

, , , , , , , , , , ,
Erlotinib after Gefitinib failure in female never-smoker Asian patients with pulmonary adenocarcinoma.
Lung Cancer. 2009;65(2):204-7.

Abstract
The activity of erlotinib after gefitinib failure in non-small cell lung cancer patients with all four favorable clinical factors including female, never smoker, Asian, and adenocarcinoma histology for tyrosine kinase inhibitors (TKIs) is not well known. Treatment efficacy of erlotinib (150mg daily) after progression on gefitinib (250mg daily) was analyzed in patients exhibiting the four clinically favorable factors. Sixteen consecutive female, never smoker, Korean (Asian), adenocarcinoma patients who received erlotinib after gefitinib failure were analyzed. The disease control rate for gefitinib was 68.8% (95% CI, 0.44-0.86) while the disease control rate for erlotinib following gefitinib failure was 25.0% (95% CI, 0.10-0.50) comprised of one partial response and three stable disease patients. The median progression free survival was 6.3 months for gefitinib treatment and 1.7 months for erlotinib treatment following gefitinib failure. The efficacy of erlotinib after progression on gefitinib is unsatisfactory in patients with four favorable clinical factors for TKIs. Novel treatment approaches such as the use of irreversible TKIs or anti-cMET agents for those patients are warranted.
PubMed IF 5.3 혈액종양내과
972009

제1저자 김희준 · 교신저자 김유정

, , , , , , , , , , ,
Patterns of palliative procedures and clinical outcomes in patients with advanced non-small cell lung cancer.
Lung Cancer. 2009;65(2):242-6.

Abstract
BACKGROUND Despite recent progress in palliative chemotherapy for advanced non-small cell lung cancer (NSCLC), the prognosis is still poor. Aside from multiple lines of chemotherapy, many patients need palliative procedures due to disease-related events. The patterns of events requiring palliative procedures and their impact on the clinical course have not been well described.
METHODS We evaluated 162 patients who were diagnosed with stage IIIB (with malignant effusion) or IV NSCLC at Seoul National University Hospital in 2005. The patterns of disease-related events requiring palliative procedures, the palliative procedures given, and the clinical outcomes were retrospectively analyzed.
RESULTS Of the 162 patients, 107 were male (66%) and 55 were female (34%) with a median age of 61 years (range 31-90). Among these patients, 108 patients (66%) received palliative procedures due to disease-related events. Forty-nine patients (30%) needed a palliative procedure at the time of diagnosis, and 59 patients (36%) required palliative procedure later during the course of their treatment. The events requiring palliative procedures were thoracic events (malignant effusion or severe pneumonia requiring intensive care unit care not related to treatment) in 32 (30%), CNS events (brain metastasis or leptomeningeal metastasis) in 37 (34%), skeletal events (bone metastasis requiring radiation, spinal cord compression, hypercalcemia) in 29 (27%), and other events in 10 (9%). The patients who had events at the time of diagnosis showed comparable overall survival to the patients without events at the time of diagnosis (14.6 months vs. 13.3 months, p=0.65). The patients with later events during their course of treatment had a short median survival after the event requiring palliative procedures (median 2.7 months, 95% CI 2.19-3.21).
CONCLUSION A considerable proportion of patients with advanced NSCLC receive palliative procedures apart from chemotherapy. These interventions should be taken into consideration for comprehensive cancer care and timely cooperation with palliative care team.
PubMed IF 5.3 혈액종양내과
962009

제1저자 윤원재 · 교신저자 류지곤

, , , , , , , ,
A comparison of metal and plastic stents for the relief of jaundice in unresectable malignant biliary obstruction in Korea: an emphasis on cost-effectiveness in a country with a low ERCP cost.
Gastrointest Endosc. 2009;70(2):284-9.

Abstract
BACKGROUND In countries where ERCP costs are low relative to those of metal stents (eg, Korea), initial endoscopic retrograde biliary drainage (ERBD) with a plastic stent is thought to be more economical.
OBJECTIVE We conducted this study to compare metal and plastic stent-based ERBD in efficacy, complications, and total cost of biliary drainage.
DESIGN Retrospective study.
SETTING Tertiary referral center.
PATIENTS A total of 112 patients who had not undergone previous biliary drainage procedures and who underwent ERBD for unresectable malignant biliary obstruction.
INTERVENTIONS Endoscopic sphincterotomy was performed, and covered or uncovered Wallstents were used in 56 patients and plastic stents in 56 patients.
RESULTS Stent occlusion occurred in 31 patients after a mean of 278 days in the metal stent group and in 39 patients after a mean of 133 days in the plastic stent group (P = .0004). The incidence of and length of hospitalization for cholangitis were significantly lower in the metal stent group. There was no difference in the total number of drainage procedures between the 2 groups. There was no statistical difference in the mean cost of the relief of jaundice between the 2 groups ($1488.77 in the metal stent group vs $1319.26 in the plastic stent group, P = .422).
LIMITATIONS Nonrandomized, retrospective study.
CONCLUSION Even in countries where ERCP costs are lower than those of metal stents, ERBD with metal biliary stents as the first-line treatment may offer better palliation without a significant increased cost in patients with unresectable malignant biliary obstruction.
PubMed IF 8 소화기내과
952009

제1저자 최훈성 · 교신저자 조영민

, , , , ,
Cerebral white matter hyperintensity is mainly associated with hypertension among the components of metabolic syndrome in Koreans.
Clin Endocrinol (Oxf). 2009;71(2):184-8.

Abstract
BACKGROUND Cerebral white matter hyperintensity (WMH) is a common abnormality in brain magnetic resonance imaging (MRI) and is known to be associated with ischaemic stroke. Previous studies revealed that the risk factors for cerebral WMH were age, female gender, hypertension and diabetes. In this study we examined the association between cerebral WMH and metabolic syndrome, a cluster of hypertension, glucose intolerance, abdominal obesity and dyslipidaemia.
METHODS AND RESULTS We reviewed the results of brain MRI of 5498 subjects who underwent routine check-ups including laboratory tests at the Seoul National University Health Care System. Among the subjects who met the inclusion criteria (n = 5104), 1693 (33.2%) had cerebral WMH. They were characterized by old age, female predominance, higher body mass index (BMI), larger waist circumference, higher blood pressure, higher fasting plasma glucose level, and higher haemoglobin A1c (HbA1c). In multivariate analyses, age, female gender and hypertension were the independent risk factors for cerebral WMH. Metabolic syndrome was associated with cerebral WMH after adjusting for age and gender [odds ratio (OR) 1.20, 95% confidence interval (CI) 1.04-1.39, P = 0.014]. Among the components of metabolic syndrome, hypertension was independently associated with cerebral WMH (OR 1.20, 95% CI 1.05-1.38, P = 0.007).
CONCLUSION Age, female gender and hypertension were risk factors for cerebral WMH in the Korean population. Cerebral WMH was also associated with metabolic syndrome; however, metabolic syndrome offered no advantage over hypertension alone in predicting cerebral WMH.
PubMed IF 2.8 내분비대사내과
942009

제1저자 김용진 · 교신저자 김효수

, , , , , , , , , ,
The effect of granulocyte-colony stimulating factor on endothelial function in patients with myocardial infarction.
Heart. 2009;95(16):1320-5.

Abstract
OBJECTIVE The effects of granulocyte-colony stimulating factor (G-CSF) on endothelial function are unknown. Therefore, we investigated the effects of G-CSF on endothelial function.
METHODS 76 patients participating in the MAGIC-Cell-3-DES trial were enrolled. These were patients with acute myocardial infarction (AMI) or old MI (OMI) who underwent percutaneous coronary intervention (PCI), and were prospectively randomised into a G-CSF group (G-CSF (10 microg/kg/day) injection for 3 days after PCI) or a control group. Additionally, 20 healthy volunteers were also enrolled. These subjects were categorised into five groups: AMI-control (n = 18), AMI-G-CSF (18), OMI-control (20), OMI-G-CSF (20) and healthy-G-CSF (20). Baseline flow-mediated dilation (FMD) of the brachial artery and serum inflammatory biomarkers were performed on day 1, and repeated on day 4 in all groups. G-CSF was injected for 3 days between days 1 and 4 in the AMI-G-CSF, OMI-G-CSF and healthy-G-CSF groups.
RESULTS In both the healthy-G-CSF and OMI-G-CSF groups, G-CSF increased serum high sensitivity C-reactive protein (hsCRP) (0.3 (0.5) mg/l vs 6.1 (3.5) mg/l and 5.6 (3.8) mg/l vs 13.0 (7.7) mg/l, baseline vs post-G-CSF in the healthy and OMI-G-CSF groups, respectively, p<0.001). In the AMI-G-CSF group, G-CSF hindered the decline of hsCRP during the recovery phase, resulting in a relative increase in hsCRP. However, in all three groups, G-CSF did not significantly alter FMD.
CONCLUSION Despite an associated increase in systemic inflammation, G-CSF treatment does not lead to acute impairment of brachial artery endothelial function in either healthy subjects or patients with MI.
PubMed IF 4.4 순환기내과
932009

제1저자 장성아 · 교신저자 김효수

, , , , , , ,
Peripheral blood stem cell mobilisation by granulocyte-colony stimulating factor in patients with acute and old myocardial infarction for intracoronary cell infusion.
Heart. 2009;95(16):1326-30.

Abstract
BACKGROUND/AIMS Peripheral blood stem cells (PBSC) are one of the most promising stem cell sources for treatment of ischaemic heart disease. However, the experience of mobilisation and collection of PBSC using granulocyte-colony stimulating factor (G-CSF) in patients with myocardial infarction (MI) is still limited. We report our experiences with the feasibility and safety of collection of mobilised PBSC with G-CSF in MI patients, and the influence of acute ischaemia on efficacy of PBSC collection.
METHODS 74 patients with acute or old myocardial infarction (AMI vs OMI, n = 46 and n = 28) underwent PBSC collection after administration of G-CSF twice a day at a dose of 5 microg/kg for 3 days. Flow cytometric analysis of cell surface markers was performed.
RESULTS No evidence of inflammation or ischaemia was observed during G-CSF mobilisation and PBSC collection. The yield of CD34(+) cells was 12.9 (SD 15.92) x10(9)/l (5.04% (5.30%) of total cells) with a product volume of 37.9 (8.4) ml after 5650 (987) ml of blood were processed during PBSC collection. Stem cell mobilisation and collection by G-CSF is more efficient in AMI than in OMI, and proportions of cells positive for VE-cadherin or KDR/CD34 are significantly greater in AMI than in OMI (p<0.01).
CONCLUSION We could obtain sufficient numbers of PBSC for intracoronary infusion with the G-CSF-based mobilisation strategy without complications even in patients with MI. PBSC collection after mobilisation with G-CSF is a safe and feasible method of stem cell collection for therapeutic purpose in patients with MI.
PubMed IF 4.4 순환기내과
922009

제1저자 김범석 · 교신저자 임석아

, , , , , , , , , , , , , , , ,
Clinical significance of axillary nodal ratio in stage II/III breast cancer treated with neoadjuvant chemotherapy.
Breast Cancer Res Treat. 2009;116(1):153-60.

Abstract
PURPOSE Neoadjuvant chemotherapy may modify the yield of involved axillary lymph nodes. The purpose of this study was to identify the clinical significance of the involved nodal ratios in patients with stage II/III breast cancer treated with neoadjuvant chemotherapy.
METHODS Two hundred and five stage II and III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this prospective study. The patients received three cycles of neoadjuvant chemotherapy followed by curative surgery, either breast-conserving surgery or mastectomy with axillary lymph node dissection, and received three additional cycles of docetaxel/doxorubicin chemotherapy as adjuvant. Adjuvant radiotherapy and hormonal therapy were given after adjuvant chemotherapy when indicated.
RESULTS The median follow-up duration was 28.9 months. The overall response rate (RR) for neoadjuvant chemotherapy was 77.6%. The mean nodal ratio was 0.29 (range, 0-1.0; nodal ratio <or=0.25, 121 [59.0%] vs. >0.25, 84 [41.0%]). Relapse free survival (RFS) of the patients who had a nodal ratio >0.25 was significantly shorter (Hazard Ratio (HR) = 2.701, P = 0.001). A nodal ratio >0.25 was also associated with a shorter overall survival (OS) (HR = 4.109, P = 0.006). However, RFS and OS were not different according to the absolute number of involved nodes (ANIN) (P = 0.166, P = 0.248, respectively). In multivariate analysis, the nodal ratio was an independent prognostic factor for RFS and OS (HR = 4.246, P < 0.001; HR = 7.764, P < 0.001).
CONCLUSION Axillary nodal ratios have an independent prognostic value in stage II/III breast cancer treated with neoadjuvant chemotherapy. Nodal ratio might be a useful tool to identify the patients at high risk of relapse in the neoadjuvant setting.
PubMed IF 3.3 혈액종양내과
912009

제1저자 임수 · 교신저자 장학철

, , , , , , , ,
Comprehensive evaluation of coronary arteries by multidetector-row cardiac computed tomography according to the glucose level of asymptomatic individuals.
Atherosclerosis. 2009;205(1):156-62.

Abstract
BACKGROUND Early detection of atherosclerosis in individuals with diabetes is important because of high cardiovascular mortality in this population. We performed multidetector-row computed tomography (MDCT) in asymptomatic individuals to investigate the status of coronary artery stenosis and plaque characteristics depending on the glucose level.
METHODS AND RESULTS The plaque burden (number of diseased coronary segments), severity of stenosis, plaques characteristics, and coronary artery calcium score (CACS) were assessed by MDCT in 1043 asymptomatic individuals. Anthropometric parameters and metabolic profiles were also acquired. Twenty-one percents of subjects had plaques and 5% had significant stenosis. Mean (+/-S.D.) CACS of study population was 17+/-81. Subjects with impaired fasting glucose (IFG, n=215, 21%) or diabetes (n=112, 11%) had a greater plaque burden, more coronary stenosis (>50% of diameter stenosis) and higher CACS than normal subjects (all, p<0.01). Noncalcified and mixed plaques were observed more in subjects with diabetes (19%) and IFG (11%) than normal (7%). After adjustment for confounding factors, higher fasting glucose was strongly associated with significant coronary stenosis and a greater plaque burden.
CONCLUSIONS More significant coronary stenosis and multivessel involvement, higher CACS, and greater plaque burden were observed in subjects with IFG or diabetes by MDCT, even they are asymptomatic. Proactive screening, irrespective of the imaging modalities used, in asymptomatic subjects with prediabetes and diabetes is helpful to identify those who have a higher cardiovascular morbidity and mortality. Further studies will guide us with respect to which imaging modality is more appropriate.
PubMed IF 7.1 내분비대사내과
902009

제1저자 이은실 · 교신저자 김나영

, , , , , , , ,
Comparison of risk factors and clinical responses to proton pump inhibitors in patients with erosive oesophagitis and non-erosive reflux disease.
Aliment Pharmacol Ther. 2009;30(2):154-64.

Abstract
BACKGROUND There has been no report on the response to proton pump inhibitor (PPI) therapy and on-demand or the relapse rate of non-erosive reflux disease (NERD) and erosive oesophagitis in Korea.
AIM To compare the risk factors, clinical symptoms and PPI responses between patients with erosive oesophagitis and NERD patients.
METHODS A survey was performed prospectively in the erosive oesophagitis (205 patients) and NERD group (200 patients). Clinical symptoms, risk factors and PPI responses were analysed. On-demand therapy and the relapse rate of GERD symptoms were investigated during a one-year follow-up.
RESULTS BMI > or = 25 (OR 3.0, 95% CI 1.1-8.3), alcohol use (OR 2.9, 95% CI 1.0-8.3), hiatal hernia (OR 5.0, 95% CI 1.2-20) and triglyceride > or =150 mg/dL (OR 4.0, 95% CI 1.7-10) were more common in the erosive oesophagitis group than in the NERD group by multivariate analysis. The ratio of oesophageal to extra-oesophageal symptoms was higher in the erosive oesophagitis group compared with the NERD group (P < 0.001). The PPI response rates at 8 weeks were different (P = 0.02); refractory rates were higher in the NERD group (16.7%) compared with the erosive oesophagitis group (6.0%). However, there was no significant difference between the two groups in on-demand therapy or the relapse rate.
CONCLUSION These results suggest that the underlying pathogenic mechanisms of erosive oesophagitis and NERD are distinct.
PubMed IF 6.8 소화기내과
892009

제1저자 명선정 · 교신저자 윤정환

, , , , ,
Heat shock protein 90 inhibitor induces apoptosis and attenuates activation of hepatic stellate cells.
J Pharmacol Exp Ther. 2009;330(1):276-82.

Abstract
Activated hepatic stellate cells (HSCs) are major participants in hepatic fibrosis; thus, the induction of HSC apoptosis has been proposed as an antifibrotic treatment strategy. Heat shock protein (Hsp) 90 is a molecular chaperone that stabilizes major signal transduction proteins, and its inhibitors have antitumor activity. In this study, the susceptibility of HSCs to an Hsp90 inhibitor was evaluated. LX-2 cells, an immortalized human HSC line, 17-(allylamino)-17-demethoxygeldanamycin (17AAG), an Hsp90 inhibitor, and monensin, an acidic sphingomyelinase inhibitor, were used in this study. Cellular apoptosis was quantified by 4',6-diamidino-2-phenylindole dihydrochloride staining, and signaling cascades were explored using immunoblotting and immunoprecipitation techniques. Nuclear factor (NF) kappaB activities were evaluated by immunofluorescent microscopy and enzyme-linked immunosorbent assay. Collagen alpha1 and alpha-smooth muscle actin expressions were determined by real-time reverse transcription-polymerase chain reaction and immunoblotting, respectively. It was found that 17AAG induced HSC apoptosis and that caspase 8 cleavage preceded the downstream activation of apoptotic signaling cascades. Furthermore, this caspase 8 activation was dependent on ceramide generation by acidic sphingomyelinase. In addition, 17AAG prevented NFkappaB nuclear translocation and activation, specifically by inducing complex formation between NFkappaB and the glucocorticoid receptor. In accordance, NFkappaB-dependent cellular FLICE-like inhibitory protein expression level was found to be reduced by 17AAG. Finally, 17AAG down-regulated collagen alpha1 and alpha-smooth muscle actin expression levels in HSCs before inducing apoptosis. These results demonstrate that the Hsp90 inhibitor induces HSC apoptosis via a sphingomyelinase- and NFkappaB-dependent mechanism. Because this inhibitor also reduces HSC activation before apoptosis, Hsp90 inhibitor treatment might be therapeutically useful as an antifibrotic strategy in a variety of liver diseases.
PubMed IF 4.3 소화기내과
882009

제1저자 이현규 · 교신저자 이세훈

, , , , , , , , , , ,
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective for leptomeningeal metastasis from non-small cell lung cancer patients with sensitive EGFR mutation or other predictive factors of good response for EGFR TKI.
Lung Cancer. 2009;65(1):80-4.

Abstract
The purpose of this study was to demonstrate the beneficial effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the treatment of leptomeningeal metastasis (LM) for a select group of non-small cell lung cancer (NSCLC) patients who had a sensitive EGFR mutation or good predictive clinical factors for EGFR TKI treatment. Eleven patients with NSCLC and LM were treated with a standard dose of erlotinib (n=9), or higher than standard dose of gefitinib followed by erlotinib (n=2). They were treated with various therapies including whole brain radiotherapy or intrathecal chemotherapy for CNS lesion previously and concurrently with EGFR TKI. Nine of 11 patients showed overt improvement in ECOG performance status. Six patients were alive >6 months, and 2 additional patients were alive 2.5+ and 4.4+ months with clinical improvement. Two patients showed responses to higher than standard dose of gefitinib. The median overall survival was not reached. In conclusion, EGFR TKIs are effective in the treatment of LM from NSCLC when patients were selected properly.
PubMed IF 5.3 혈액종양내과
872009

제1저자 양기영 · 교신저자 류지곤

, , , , , ,
A comparison of the Niti-D biliary uncovered stent and the uncovered Wallstent in malignant biliary obstruction.
Gastrointest Endosc. 2009;70(1):45-51.

Abstract
BACKGROUND The conformability of uncovered self-expandable metal stents (SEMSs) plays an important role in maintaining stent patency. However, whether increased conformability can prolong the duration of SEMS patency remains to be proved.
OBJECTIVE The aim of this study was to examine the efficacy and complication rates of the Niti-D biliary uncovered metal stent (NDS), which is more conformable than the uncovered Wallstent.
DESIGN Nonrandomized, retrospective study.
SETTING Tertiary-care academic medical center.
PATIENTS From March 2005 to July 2007, 101 patients received an NDS (41 cases) or a Wallstent (60 cases) for malignant biliary obstruction.
INTERVENTIONS SEMS placement.
RESULTS Stent occlusion occurred in 11 patients (26.8%) with the NDS and 17 patients (28.3%) with the Wallstent. The median duration of stent patency tended to be longer for the NDS group (153 days) than for the Wallstent group (124 days); however, the difference was not statistically significant (P = .204). The median duration of overall survival of patients was 160 days for the NDS and 148 days for the Wallstent. The subgroup analysis showed that 27 patients had hilar obstruction (NDS 13, Wallstent 14). The median duration of stent patency was 249 days for the NDS group and 76 days for the Wallstent group; this difference was statistically significant (P = .006). The complications included pancreatitis in 3 NDS cases and 5 Wallstent cases.
LIMITATION The absence of prospective randomized recruitment.
CONCLUSION The results of this study showed no significant differences between the NDS and the Wallstent for the palliative endoscopic management of malignant biliary obstruction. There were no significant differences in patency, complication rates, and patient survival between the more conformable NDS and the conventional Wallstent. However, the NDS, which has good conformability, may be preferred for hilar obstruction.
PubMed IF 8 소화기내과

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