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The Epidermal Growth Factor Receptor Signalings in Human Cholangiocarcinomas
( Geum Youn Gwak ),( Jung Hwan Yoon ),( Kang Mo Kim ),( Hyo Suk Lee ),( Chung Yong Kim ) 대한소화기학회 2003 대한소화기학회 추계학술대회 Vol.2003 No.-
<Background & Aims> We have recently demonstrated that bile acids appear to participate in the genesis and progression of cholangiocarcinoma via activation of the epidermal growth factor receptor (EGFR). However, the characteristics of EGFR signaling in c
Bile Acid-induced JNK Activation Directly Initiates Mitochondrial Cytochrome C Release
( Geum Youn Gwak ),( Jung Hwan Yoon ),( Kang Mo Kim ),( Hyo Suk Lee ),( Chung Yong Kim ) 대한소화기학회 2003 대한소화기학회 추계학술대회 Vol.2003 No.-
<Background & Aims> In cholestasis, elevated bile acid concentrations within the liver promote liver injury by inducing hepatocyte apoptosis. Bile acid-induced apoptotic process primarily involves death receptor-mediated signaling cascades. Bile acids can
Gwak, Geum-Youn,Yoon, Jung-Hwan,Yu, Su Jong,Park, Su Cheol,Jang, Ja June,Lee, Kyoung Bun,Lee, Sung-Hee,Lee, Soo-Mi,Shin, Chan Soo,Suh, Kyung-Suk,Lee, Hyo-Suk National Hellenic Research Foundation 2006 Oncology reports Vol.15 No.5
<P>N-cadherin signaling has recently been implicated in the progression of certain epithelial tumors by promoting invasion and dissemination of cancer cells. N-cadherin has also been reported to exert an anti-apoptotic effect. In this study, we attempted to evaluate the participation of this adhesion molecule in the progression of human hepatocellular carcinomas (HCCs) by analyzing its anti-apoptotic signaling as well as its prognostic implication in HCC patients. N-cadherin was found to be expressed in human HCCs. We established a stable human HCC cell line expressing a truncated N-cadherin, NCaddeltaC, with a dominant-negative action. NCaddeltaC-expressing cells were more susceptible to bile acid-induced apoptosis than control cells. N-cadherin was found to complex with procaspase-8, and this association was diminished in NCaddeltaC-expressing cells, leading to enhanced procaspase-8 recruitment to death-inducing signaling complex following bile acid treatment. A clinicopathological analysis in patients who had undergone surgical resection for HCC revealed that tumoral N-cadherin up-regulation was significantly related to poor recurrence-free and overall survival. Our findings implicate N-cadherin signaling as contributing to HCC progression by exerting anti-apoptotic effects. Thus, we suggest that the selective interruption of this signaling may have therapeutic potential.</P>
( Geum-youn Gwak ),( Young-suk Lim ),( Kwan Soo Byun ),( Yoon Jun Kim ),( Byung Chul Yoo ),( So Young Kwon ),( Jonggi Choi ),( Jihyun An ),( Han Chu Lee ),( Yung Sang Lee ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: Tenofovir disoproxil fumarate (TDF) monotherapy for 48 weeks displayed non-inferior efficacy to TDF plus entecavir (ETV) combination therapy in hepatitis B virus (HBV) patients resistant to ETV and lamivudine (LAM). However, whether prolonged TDF monotherapy would be safe and increase the virologic response rate in these patients is unclear. Methods: Among 90 patients with HBV resistant to ETV and LAM who were randomized to receive TDF monotherapy (n=45) or TDF/ETV combination therapy (n=45) for 48 weeks, 89 agreed to continue the study on TDF monotherapy, and 84 (93.3%) completed 144 weeks. Results: At baseline, all patients had various HBV mutations resistant to ETV and LAM (rtT184A/C/F/G/I/L/S, rtS202G, and rtM250L/V, in addition to rtM204V/I). By intention-to-treat analysis, 71.1% in the TDF-TDF group and 73.3% in the TDF/ETV-TDF group had serum HBV DNA <15 IU/mL at week 48 (P=0.81). At week 144, the proportion increased to 82.2% and 88.9%, respectively (P=0.37). By on-treatment analysis, 95.1% and 93.0%, respectively, had HBV DNA < 60 IU/mL at week 144 (P=0.68). Virologic breakthrough occurred in 2 patients in TDF-TDF group at week 48 and 120 due to poor drug adherence. At week 144, 5 patients who had HBV DNA >60 IU/mL qualified for HBV genotypic resistance tests, and 2 patients retained some of their baseline resistance mutations. No patients developed additional resistance mutations throughout the study period. Treatment was generally well tolerated. The mean change in estimated GFR from baseline was not significant at week 144 (2.07 mL/min/1.73 m2, P=0.18). The mean change in bone mineral density from baseline at week 144 was 0.32% at spine (P=0.59) and -0.92% at femur (P=0.02). Conclusions: TDF monotherapy was safe and efficacious in patients with ETV-resistant HBV for up to 144 weeks.
Gwak, Geum-Youn,Yoon, Jung-Hwan,Kim, Kang Mo,Lee, Hyo-Suk,Chung, Jin Wook,Gores, Gregory J. Elsevier 2005 Journal of hepatology Vol.42 No.3
<P><B>Background/Aims</B></P><P>In a hypoxic state, a glycolytic system is operating as a salvage pathway of generating ATP, and hexokinase II, the first enzyme in this system, might be over-expressed in hepatocellular carcinomas (HCCs). This study was to evaluate if hexokinase II is participating in HCC cell survival in a hypoxic state, and to analyze the mechanism of cell death caused by hexokinase II-specific inhibition.</P><P><B>Methods</B></P><P>Human hepatoma cell lines were grown either in a normoxic or hypoxic condition. Hexokinase II and hypoxia-inducible factor-1α (HIF-1α) expression were evaluated using immunoblot techniques. Cell growth was assessed using the MTS assay. Apoptotic signaling cascades were explored by immunoblot analysis.</P><P><B>Results</B></P><P>Hypoxia stimulated HCC cellular growth through HIF-1α-dependent induction of hexokinase II expression. The hexokinase II-specific inhibitor, 3-bromopyruvate, significantly suppressed cellular growth in a hypoxic state compared to cells in a normoxic condition. This suppression was due to the induction of apoptosis through activating mitochondrial apoptotic signaling cascades.</P><P><B>Conclusions</B></P><P>This study demonstrates that hypoxia stimulates HCC cellular growth through hexokinase II induction, and its inhibition induces apoptotic cell death. Therefore, hexokinase II induction may participate in HCC progression and the blockage of this enzyme may therapeutically be efficacious in human HCCs.</P>
( Geum-youn Gwak ),( Young-suk Lim ),( Jonggi Choi ),( Kwan Soo Byun ),( Yoon Jun Kim ),( Byung Chul Yoo ),( So Young Kwon ),( Han Chu Lee ),( Yung Sang Lee ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: To demonstrate whether tenofovir alafenamide (TAF) is efficacious in patients with hepatitis B virus (HBV) resistant to multiple drugs Methods: This was a randomized trial to assess whether switching tenofovir disoproxil fumarate (TDF) to TAF shows non-inferior efficacy and better safety profile in patients with multidrug-resistant HBV compared to continuing TDF. Patients with HBV resistant to entecavir and/or adefovir under TDF monotherapy for at least 96 weeks were randomized 1:1 to switch to TAF or continue TDF for 48 weeks. The primary efficacy endpoint was the proportion of patients with HBV DNA <60 IU/mL in the full analysis set. Results: Of 174 eligible patients under TDF monotherapy, 87 switched to TAF and 87 continued TDF. At baseline, 163 (93.7%) patients had HBV DNA less than 60 IU/mL (96.6% in TAF group vs. 90.8% in TDF group). At week 48, the proportion of patients with HBV DNA <60 IU/mL was 98.9% in TAF group, which was non-inferior to TDF group (97.8%; P=0.99). The proportion of patients with normal ALT (<=40 IU/L) at week 48 tended to be higher in TAF group compared with TDF group (92.0% vs. 79.3%; P=0.06). TAF group showed a significantly higher increase in bone mineral density (BMD) at spine compared with TDF group at week 48 (mean% change, +1.84% vs. 0.08%; P=0.01). TAF group, compared to TDF group, tended to show a larger increase in estimated glomerular filtration rate from baseline as measured by Cockcroft-Gault formula (mean % change, +8.2% vs. +4.5%; P=0.06). Conclusions: In CHB patients with multidrug-resistant HBV, switching TDF to TAF was as effective as TDF in virologic response with improved bone and renal safety.
특 집 -C형 간염의 치료 : 특수한 경우의 C형 간염 치료: 간경변증
곽금연 ( Geum Youn Gwak ) 대한내과학회 2015 대한내과학회지 Vol.88 No.6
Acquiring a sustained virological response (SVR) in patients with cirrhosis or advanced hepatic fibrosis reduces liver disease- related mortality and the incidence of hepatocellular carcinoma. However, the SVR rate of the current standard of care, which is combination therapy with peg-interferon-alpha and ribavirin, is significantly lower, and treatment-related complications occur more frequently in patients with cirrhosis. Thus, antiviral treatment should be individualized in this population. This review highlights the issues associated with anti-hepatitis C virus treatment in patients with compensated and decompensated cirrhosis. (Korean J Med 2015;88:643-646)