SCI 발표논문
2008년 130편
- 102008
제1저자 이해영 · 교신저자 김효수
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FOXO3a turns the tumor necrosis factor receptor signaling towards apoptosis through reciprocal regulation of c-Jun N-terminal kinase and NF-kappaB.Arterioscler Thromb Vasc Biol. 2008;28(1):112-20.
PubMed IF 8.8 순환기내과Abstract
OBJECTIVE We evaluated the full range effects of FOXO3a in endothelial cells (ECs) by microarray analysis and investigated the role of FOXO3a regulating TNF receptor signaling pathway.
METHODS AND RESULTS Human umbilical vein endothelial cells (HUVECs) were transfected with adenoviral vectors expressing constitutively active FOXO3a (Ad-TM-FOXO3a). Ad-TM-FOXO3a transfection caused remarkable apoptosis, which were accompanied with upregulation of genes related with TNF receptor signaling, such as TNF-alpha, TANK (TRAF-associated NF-kappaB activator), and TTRAP (TRAF and TNF receptor-associated protein). Furthermore, kappaB-Ras1 (IkappaB-interacting Ras-like protein-1) which is known to block IkappaB degradation was found increased, and intranuclear translocation of NF-kappaB was inhibited. GADD45beta and XIAP, negative regulators of c-Jun N-terminal kinase (JNK), were suppressed and JNK activity was increased. Attenuation of TNF signaling pathway either by blocking antibody for TNF receptor or by blocking JNK with DMAP (6-dimethylaminopurine) or Ad-TAM67 (dominant negative c-Jun) cotransfection, significantly reduced FOXO3a-induced apoptosis. Finally, treatment of vasculature with heat shock, an activator of endogenous FOXO3a, resulted in EC apoptosis, which was completely rescued by Ad-TAM67.
CONCLUSIONS FOXO3a promotes apoptosis of ECs, through activation of JNK and suppression of NF-kappaB. These data identify a novel role of FOXO3a to turn TNF receptor signaling to a proapoptotic JNK-dependent pathway.
- 92008
제1저자 김선영 · 교신저자 방영주
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Trastuzumab inhibits the growth of human gastric cancer cell lines with HER2 amplification synergistically with cisplatin.Int J Oncol. 2008;32(1):89-95.
PubMed IF 7.3 혈액종양내과Abstract
HER2 has been found to be amplified in 10-20% of gastric cancers, and is correlated with poor outcome. The aims of this study were to recognize HER2 amplification in gastric cancer cell lines via fluorescence in situ hybridization and to evaluate the growth inhibitory effect of trastuzumab in HER2-amplified cell lines. To elucidate the mechanism of the growth inhibition, we performed cell cycle analysis and immunoblotting of downstream molecules. We also conducted drug interaction studies of trastuzumab with other chemotherapeutic agents. HER2 amplification was newly identified only in SNU-216 cells, and trastuzumab moderately inhibited the growth of SNU-216 cells and positive controls. Trastuzumab-mediated G1 arrest occurred with increased expression of p27(KIP1) and decreased cyclins. Phosphorylation of HER2 and downstream molecules, STAT3, AKT, and ERK, was also inhibited by trastuzumab. Treatment of SNU-216 cells with trastuzumab plus cisplatin resulted in a synergistic inhibitory effect, whereas treatment of SNU-216 cells with trastuzumab plus 5-FU, or trastuzumab plus oxaliplatin produced an additive effect. These results suggest that trastuzumab combined with chemotherapeutic agents can be active against gastric cancer with HER2 amplification.
- 82008
제1저자 우상명 · 교신저자 류지곤
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Survival and prognosis of invasive intraductal papillary mucinous neoplasms of the pancreas: comparison with pancreatic ductal adenocarcinoma.Pancreas. 2008;36(1):50-5.
PubMed IF 2.2 소화기내과Abstract
OBJECTIVES Invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas is often considered to have a better prognosis than pancreatic ductal adenocarcinoma. The aim of this study was to evaluate and compare the prognosis and clinicopathologic features between 2 groups.
METHODS Clinicopathologic features and long-term outcome of 32 patients with invasive IPMN were retrospectively evaluated and compared with those of 332 patients with pancreatic ductal adenocarcinoma.
RESULTS Asymptomatic patients were more frequently observed in the group of invasive IPMN than ductal adenocarcinoma (28% vs 11%, P = 0.013). The distribution of stages of invasive IPMN was as follows: stage I (n = 10, 31%), II (n = 8, 25%), III (n = 3, 9%), and IV (n = 11, 34%). Among 19 patients who underwent resection for invasive IPMN, 10 (53%), 1 (5%), 1 (5%), and 2 (11%) had T1 stage tumors and tumor with lymph node metastasis, lymphatic, and perineural invasions, respectively, which were significantly infrequently observed compared with those with ductal adenocarcinoma. The 5-year survival rate of invasive IPMN was 33.9% compared with 9% of ductal adenocarcinoma (P = 0.011). The difference in the mean survival rates between invasive IPMN and ductal adenocarcinoma in patients without metastasis was also significant but not in patients with metastasis. During the median follow-up period of 18.4 months, 3 patients (16%) had a recurrence after resection for invasive IPMN.
CONCLUSIONS Both the less aggressive pathological factors concerned with tumor invasiveness and early diagnosis of invasive IPMN contribute to higher survival rates of invasive IPMN than ductal adenocarcinoma. However, the prognosis of metastatic invasive IPMN is as poor as that of ductal adenocarcinoma.
- 72008
제1저자 강형민 · 교신저자 김나영
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Effects of Helicobacter pylori Infection on gastric mucin expression.J Clin Gastroenterol. 2008;42(1):29-35.
PubMed IF 2.7 소화기내과Abstract
AIMS This study was performed to determine the gastric distributions of MUC5AC and MUC6 depending on Helicobacter pylori (H. pylori) infection, and to evaluate whether the expressions of MUC5 and MUC6 change in H. pylori-associated gastroduodenal diseases. In addition, MUC5AC and MUC6 expressional changes were investigated before and after H. pylori eradication.
METHODS In the 224 individuals (136 H. pylori-positive and 88 H. pylori-negative) who came from control (N=48), duodenal ulcer (N=35), benign gastric ulcer (N=61), dysplasia plus stomach cancer (N=80) groups, MUC5AC and MUC6 expressions were determined by immunohistochemical staining in the antrum and body, respectively. This staining for MUC5AC and MUC6 were reperformed in 113 of the 136 H. pylori-positive patients after successful H. pylori eradication by proton pump inhibitor-based triple therapy.
RESULTS (1) No difference was found between the H. pylori-positive and negative groups in terms of MUC5AC expression. In contrast, MUC6 expression was significantly lower in the H. pylori-positive group than in the H. pylori-negative group in the gastric body. Moreover, reduced MUC6 expression increased to the H. pylori-negative level after eradication. (2) Expressions of MUC5AC and MUC6 were significantly lower in the dysplasia plus cancer group than those of control in case of H. pylori positive. Similarly, MUC5AC and MUC6 expressions were significantly lower in the presence of atrophic gastritis with intestinal metaplasia in case of H. pylori positive. (3) Aberrant expressions of MUC6 in foveolar cells were observed in both antrum (11.3%) and body (5.3%) only in the H. pylori-positive group, but this reverted to normal after H. pylori eradication.
CONCLUSION These results suggest that H. pylori infection causes alterations of mucin expression, closely related with the development of gastric atrophy with intestinal metaplasia, probably contributing to carcinogenesis.
- 62008
제1저자 김나영 · 교신저자 김나영
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Helicobacter pylori infection and development of gastric cancer in Korea: long-term follow-up.J Clin Gastroenterol. 2008;42(5):448-54.
PubMed IF 2.7 소화기내과Abstract
BACKGROUND AND AIM Infection of Helicobacter pylori is viewed as a major driver of progression to the precancerous state or to gastric cancer. This study was performed to investigate the effect of H. pylori infection on gastric cancer development and to determine to what extent H. pylori eradication is likely to reduce the prevalence of gastric cancer.
METHODS Gastric cancer development was investigated in 1790 Korean subjects who underwent gastroscopy and H. pylori testing between 1992 and 1998. The effects of H. pylori-positive and eradicated states on gastric cancer development were analyzed.
RESULTS Gastric cancer developed in 5 of the study cohort during a mean follow-up period of 9.4 years. All of these patients were positive for H. pylori infection, and 4 of the 5 had antral intestinal metaplasia (IM) at the time of study enrollment. One of these 5 patients was in an eradicated state when the gastric cancer was diagnosed, and had histologic IM before eradication therapy was performed. Gastric cancer was found to develop 10.9 times more frequently in the presence of IM than in its absence.
CONCLUSIONS The present study shows a close relationship between H. pylori infection and IM, and between IM and the development of gastric cancer. In addition, our finding suggests that chronic H. pylori infection looks like an important risk factor for the development of gastric cancer in Korea, where the prevalence of H. pylori remains high. This study indicates that to prevent gastric cancer H. pylori eradication is best performed before the development of IM.
- 52008
제1저자 최인호 · 교신저자 김재영,안규리
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Xenogeneic interaction between human CD40L and porcine CD40 activates porcine endothelial cells through NF-kappaB signaling.Mol Immunol. 2008;45(2):575-80.
PubMed IF 3.7 신장내과Abstract
Xenotransplantation is a promising alternative to overcome donor shortage in transplantation. CD40 molecule plays an important role in the interaction of T cells with antigen-presenting cells and in the activation of vascular endothelial cells. We investigated whether the xenogeneic interaction between human CD40L (hCD40L) on T cells and porcine endothelial CD40 (pCD40) can activate porcine endothelial cells (PECs). The interaction between hCD40L and pCD40 induced the expression of chemokines on PECs as well as MHC and adhesion molecules. Furthermore, NF-kappaB signaling was activated in HEK 293 cells expressing pCD40 and PECs by stimulation with hCD40L+ Jurkat T clones. Both anti-CD40L neutralizing antibodies and NF-kappaB signal inhibitors interfered with immune activation of PECs. Overall, this study shows that xenogeneic interaction between hCD40L and pCD40 can activate PECs through NF-kappaB signaling, and therefore may contribute to acute vascular rejection in xenotransplantation.
- 42008
제1저자 김성한 · 교신저자 오명돈
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Outcome of vancomycin treatment in patients with methicillin-susceptible Staphylococcus aureus bacteremia.Antimicrob Agents Chemother. 2008;52(1):192-7.
PubMed IF 4.2 감염내과Abstract
Limited data on the clinical outcome of vancomycin treatment compared with that of beta-lactam treatment in patients with methicillin-susceptible Staphylococcus aureus bacteremia (MSSA-B) are available. We used different and complementary approaches: (i) a retrospective cohort study using a propensity score to adjust for confounding by treatment assignment and (ii) a matched case-control study. Of all patients with S. aureus bacteremia (SAB) in two university-affiliated hospitals over a 7-year period, 294 patients with MSSA-B were enrolled in the cohort study. The cases for the case-control study were defined as patients who received vancomycin treatment for MSSA-B; the controls, who were patients that received beta-lactam treatment for MSSA-B, were selected at a 1:2 (case:control) ratio according to the objective matching scoring system and the propensity score system. In the cohort study, SAB-related mortality in patients with vancomycin treatment (37%, 10/27) was significantly higher than that in those with beta-lactam treatment (18%, 47/267) (P = 0.02). In addition, multivariate analysis revealed that vancomycin treatment was associated with SAB-related mortality when independent predictors for SAB-related mortality and propensity score were considered (adjusted odds ratio of 3.3, 95% confidence interval of 1.2 to 9.5). In the case-control study using the objective matching scoring system and the propensity score system, SAB-related mortality in case patients was 37% (10/27) and in control patients 11% (6/54) (P < 0.01). Our data suggest that vancomycin is inferior to beta-lactam in the treatment of MSSA-B.
- 32008
제1저자 이상협 · 교신저자 이동호
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Submucosal saline-epinephrine injection in colon polypectomy: appropriate indication.Hepatogastroenterology. 2008;55(86-87):1589-93.
PubMed IF 0.904 소화기내과Abstract
BACKGROUND/AIMS Opinions vary among endoscopists concerning the indications for submucosal saline-epinephrine injection for the prevention of postpolypectomy complications after colonic snare polypectomy. This study was performed to determine the appropriate indications for submucosal saline-epinephrine injection.
METHODOLOGY Clinical characteristics and complications (hemorrhage and perforation) in polypectomies were retrospectively evaluated. Postpolypectomy complications were analyzed in terms of demographic characteristics (age, gender), polyp characteristics (size, configuration, location, and histopathology), and the administration of submucosal saline-epinephrine injection.
RESULTS Total 1039 polypectomies were performed in 563 patients (age 59.8 +/- 10.1 years), and submucosal saline-epinephrine injection was performed in 679 polypectomies. Twenty seven episodes (2.6%) of hemorrhage and 3 cases (0.2%) of perforation occurred. Malignant adenoma, a rectal polyp, and procedure without submucosal saline-epinephrine injection increased the risk of hemorrhage with odds ratios of 10.48, 4.71, and 3.44, respectively. Furthermore, submucosal saline-epinephrine injection significantly reduced the risk of hemorrhage in sessile polyps and those > 8 mm in size and with odds ratio of 16.41 regardless of location or histopathology. The occurrence of postpolypectomy perforation was not associated with any clinical characteristics and method.
CONCLUSIONS Submucosal saline-epinephrine injection should be performed for sessile polyps and those > 8 mm in size, and might be performed optionally in other cases to prevent postpolypectomy hemorrhage.
- 22008
제1저자 이상협 · 교신저자 황진혁
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Does endoscopic sphincterotomy reduce the recurrence rate of cholangitis in patients with cholangitis and suspected of a common bile duct stone not detected by ERCP?Gastrointest Endosc. 2008;67(1):51-7.
PubMed IF 8 소화기내과Abstract
BACKGROUND It has not been established whether endoscopic sphincterotomy (ES) prevents subsequent cholangitis in patients with cholangitis and with a common bile duct (CBD) stone not documented by ERCP.
OBJECTIVE The aim of this study was to investigate the role of ES on the recurrence of cholangitis in patients with a high probability of having a CBD stone, not demonstrated by ERCP.
DESIGN AND PATIENTS A total of 117 patients who were diagnosed as having cholangitis and a high probability of a CBD stone, not detected by ERCP, were retrospectively reviewed. Cumulative recurrence rates of cholangitis were compared for treatments with and without ES.
SETTING Multicenter, retrospective study.
INTERVENTIONS ES.
MAIN OUTCOME MEASUREMENTS Cumulative recurrence of cholangitis after ERCP.
RESULTS Eighty-three patients underwent ES (ES group) and 34 patients did not (non-ES group). No statistically significant differences between the 2 groups were evident in terms of demographic factors or laboratory findings. The mean (standard deviation) follow-up was 22.1 +/- 17.2 months (range 3-66 months) in the ES group and 23.3 +/- 14.9 months (range 6-84 months) in the non-ES group (P = .72). The cumulative rates of cholangitis were 6.3% (4.8% vs 9.9%) at 1 year, 15.6% (9.2% vs 29.3%) at 3 years, and 19.5% (9.2% vs 52.9%) at 5 years for ES vs non-ES groups, respectively (P = .04). By multivariate analysis, ES reduced cholangitis recurrence, with a hazard ratio of 0.305 (95% CI 0.095-0.975, P = .045).
LIMITATIONS Retrospective study.
CONCLUSIONS ES reduced further episodes of cholangitis in patients with an episode of cholangitis and a high probability of choledocholithiasis, despite the lack of a CBD stone seen on ERCP.
- 12008
제1저자 박정현 · 교신저자 김태유
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Inhibitors of histone deacetylases induce tumor-selective cytotoxicity through modulating Aurora-A kinase.J Mol Med (Berl). 2008;86(1):117-28.
PubMed IF 5 혈액종양내과Abstract
The molecular basis of the antitumor selectivity of histone deacetylase inhibitors (HDIs) remains unclear. Centrosomal Aurora-A kinase regulates chromosomal segregation during mitosis. The overexpression or amplification of Aurora-A leads to genetic instability, and its inhibition has shown significant antitumor effects. In this paper, we report that structurally related hydroxamate LAQ824 and SK-7068 induce tumor-selective mitotic defects by depleting Aurora-A. We found that HDI-treated cancer cells, unlike nontransformed cells, exhibit defective mitotic spindles. After HDI, Aurora-A was selectively downregulated in cancer cells, whereas Aurora-B remained unchanged in both cancer and nontransformed cells. LAQ824 or SK-7068 treatment inhibited histone deacetylase (HDAC) 6 present in Aurora-A/heat shock protein (Hsp) 90 complex. Inhibition of HDAC6 acetylated Hsp90 and resulted in dissociation of acetylated Hsp90 from Aurora-A. As a result, Hsp70 binding to Aurora-A was enhanced in cancer cells, leading to proteasomal degradation of Aurora-A. Overall, these provide a novel molecular basis of tumor selectivity of HDI. LAQ824 and SK-7068 might be more effective HDIs in cancer cells with Aurora-A overexpression.
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