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102. Tonicity-responsive enhancer-binding protein promotes hepatocellular carcinogenesis, recurrence and metastasis

Author

Lee, Jun Ho, Suh, Jae Hee, Choi, Soo Youn, Kang, Hyun Je, Lee, Hwan Hee, Ye, Byeong Jin, Lee, Gap Ryol, Jung, Seok Won, Kim, Chang Jae, Lee-Kwon, Whaseon, Park, Jiyoung, Myung, Kyungjae, Park, Neung Hwa, and Kwon, Hyug Moo

Abstract

ObjectivesHepatocellular carcinoma (HCC) is a common cancer with high rate of recurrence and mortality. Diverse aetiological agents and wide heterogeneity in individual tumours impede effective and personalised treatment. Tonicity-responsive enhancer-binding protein (TonEBP) is a transcriptional cofactor for the expression of proinflammatory genes. Although inflammation is intimately associated with the pathogenesis of HCC, the role of TonEBP is unknown. We aimed to identify function of TonEBP in HCC.DesignTumours with surrounding hepatic tissues were obtained from 296 patients with HCC who received completion resection. TonEBP expression was analysed by quantitative reverse transcription–quantitative real-time PCR (RT-PCR) and immunohfistochemical analyses of tissue microarrays. Mice with TonEBP haplodeficiency, and hepatocyte-specific and myeloid-specific TonEBP deletion were used along with HCC and hepatocyte cell lines.ResultsTonEBP expression is higher in tumours than in adjacent non-tumour tissues in 92.6% of patients with HCC regardless of aetiology associated. The TonEBP expression in tumours and adjacent non-tumour tissues predicts recurrence, metastasis and death in multivariate analyses. TonEBP drives the expression of cyclo-oxygenase-2 (COX-2) by stimulating the promoter. In mouse models of HCC, three common sites of TonEBP action in response to diverse aetiological agents leading to tumourigenesis and tumour growth were found: cell injury and inflammation, induction by oxidative stress and stimulation of the COX-2 promoter.ConclusionsTonEBP is a key component of the common pathway in tumourigenesis and tumour progression of HCC in response to diverse aetiological insults. TonEBP is involved in multiple steps along the pathway, rendering it an attractive therapeutic target as well as a prognostic biomarker.

Published
2019
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104. Oral Administration of Gintonin Attenuates Cholinergic Impairments by Scopolamine, Amyloid-β Protein, and Mouse Model of Alzheimer’s Disease

Author

Kim, Hyeon-Joong, primary, Shin, Eun-Joo, additional, Lee, Byung-Hwan, additional, Choi, Sun-Hye, additional, Jung, Seok-Won, additional, Cho, Ik-Hyun, additional, Hwang, Sung-Hee, additional, Kim, Joon Yong, additional, Han, Jung-Soo, additional, Chung, ChiHye, additional, Jang, Choon-Gon, additional, Rhim, Hyewon, additional, Kim, Hyoung-Chun, additional, and Nah, Seung-Yeol, additional

Published
2015
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108. Clinical Course of Partial Virologic Response with Prolonged Tenofovir Therapy in Nuclos(t)ides-Naïve Patients with Chronic Hepatitis B.

Author

Jeong, In, Jung, Seok, Park, Bo, Lee, Byung, Park, Jae, Kim, Byung, Bang, Sung-Jo, Shin, Jung, Park, Neung, Du Jeong, In, Jung, Seok Won, Park, Bo Ryung, Lee, Byung Uk, Park, Jae Ho, Kim, Byung Gyu, Shin, Jung Woo, and Park, Neung Hwa

Subjects
HEPATITIS B, TENOFOVIR, CHRONIC diseases, NUCLEOSIDES, REGRESSION analysis, DNA, DRUG administration, HEPATITIS viruses, MULTIVARIATE analysis, TIME, LOGISTIC regression analysis, VIRAL load, TREATMENT effectiveness, RETROSPECTIVE studies, REVERSE transcriptase inhibitors, CHRONIC hepatitis B, ODDS ratio, DIAGNOSIS
Abstract

Background/aims: The clinical course of chronic hepatitis B (CHB) patients with partial virologic response (PVR) during tenofovir disoproxil fumarate (TDF) therapy remains unclear.Methods: We retrospectively investigated the long-term clinical outcomes of TDF treatment in nucleos(t)ides-naïve CHB patients, particularly in those with PVR.Results: A total of 391 patients treated with TDF therapy for more than 12 months were included. Virologic response (VR) was achieved in 341 patients (87.2%). PVR was evident in 127 (45.3%) of the 391 patients. Multivariate logistic regression analysis using selected baseline factors identified absolute HBV DNA levels at baseline (OR 0.496; 95% CI 1.369-1.969) and HBeAg positivity (OR 0.622; 95% CI 1.096-3.167) as factors significantly associated with PVR. During continuous prolonged TDF therapy, 127 (71.8%) of 177 patients with PVR achieved VR. The cumulative rates of VR in patients with PVR at 12, 24, and 36 months were 42.4, 79.7, and 90.2%, respectively. Serum HBV DNA level at week 24 was significantly associated with VR in patients with PVR.Conclusions: The vast majority of CHB patients with PVR achieved VR through prolonged TDF therapy, although the time to achieve VR was delayed in those with PVR. This suggests that adjustment of TDF therapy in patients with PVR is unnecessary. [ABSTRACT FROM AUTHOR]

Published
2017
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111. Ginseng Gintonin Activates the Human Cardiac Delayed Rectifier K+ Channel: Involvement of Ca2+/Calmodulin Binding Sites

Author

Choi, Sun-Hye, primary, Lee, Byung-Hwan, additional, Kim, Hyeon-Joong, additional, Jung, Seok-Won, additional, Kim, Hyun-Sook, additional, Shin, Ho-Chul, additional, Lee, Jun-Hee, additional, Kim, Hyoung-Chun, additional, Rhim, Hyewhon, additional, Hwang, Sung-Hee, additional, Ha, Tal soo, additional, Kim, Hyun-Ji, additional, Cho, Hana, additional, and Nah, Seung-Yeol, additional

Published
2014
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112. Reply

Author

Park, Neung Hwa, primary, Jung, Seok Won, additional, Shin, Eun‐Soon, additional, and Chung, Young‐Hwa, additional

Published
2014
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115. Resveratrol Inhibits Glycine Receptor-Mediated Ion Currents

Author

Lee, Byung-Hwan, primary, Hwang, Sung-Hee, additional, Choi, Sun-Hye, additional, Kim, Hyeon-Joong, additional, Jung, Seok-Won, additional, Kim, Hyun-Sook, additional, Lee, Joon-Hee, additional, Kim, Hyung-Chun, additional, Rhim, Hyewhon, additional, and Nah, Seung-Yeol, additional

Published
2014
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116. Panaxginseng as an adjuvant treatment for Alzheimer's disease

Author

Kim, Hyeon-Joong, Jung, Seok-Won, Kim, Seog-Young, Cho, Ik-Hyun, Kim, Hyoung-Chun, Rhim, Hyewhon, Kim, Manho, and Nah, Seung-Yeol

Abstract

Longevity in medicine can be defined as a long life without mental or physical deficits. This can be prevented by Alzheimer's disease (AD). Current conventional AD treatments only alleviate the symptoms without reversing AD progression. Recent studies demonstrated that Panaxginseng extract improves AD symptoms in patients with AD, and the two main components of ginseng might contribute to AD amelioration. Ginsenosides show various AD-related neuroprotective effects. Gintonin is a newly identified ginseng constituent that contains lysophosphatidic acids and attenuates AD-related brain neuropathies. Ginsenosides decrease amyloid β-protein (Aβ) formation by inhibiting β- and γ-secretase activity or by activating the nonamyloidogenic pathway, inhibit acetylcholinesterase activity and Aβ-induced neurotoxicity, and decrease Aβ-induced production of reactive oxygen species and neuroinflammatory reactions. Oral administration of ginsenosides increases the expression levels of enzymes involved in acetylcholine synthesis in the brain and alleviates Aβ-induced cholinergic deficits in AD models. Similarly, gintonin inhibits Aβ-induced neurotoxicity and activates the nonamyloidogenic pathway to reduce Aβ formation and to increase acetylcholine and choline acetyltransferase expression in the brain through lysophosphatidic acid receptors. Oral administration of gintonin attenuates brain amyloid plaque deposits, boosting hippocampal cholinergic systems and neurogenesis, thereby ameliorating learning and memory impairments. It also improves cognitive functions in patients with AD. Ginsenosides and gintonin attenuate AD-related neuropathology through multiple routes. This review focuses research demonstrating that ginseng constituents could be a candidate as an adjuvant for AD treatment. However, clinical investigations including efficacy and tolerability analyses may be necessary for the clinical acceptance of ginseng components in combination with conventional AD drugs.

Published
2018
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121. Genipin Enhances Kaposi’s Sarcoma-Associated Herpesvirus Genome Maintenance.

Author

Cho, Miyeon, Jung, Seok Won, Lee, Soomin, Son, Kuwon, Park, Gyu Hwan, Jung, Jong-Wha, Shin, Yu Su, Seo, Taegun, Hyosun Cho, null, and Kang, Hyojeung

Subjects
*KAPOSI'S sarcoma-associated herpesvirus, *KAPOSI'S sarcoma, *VIRAL genomes, *LIFE cycles (Biology), *ANTIVIRAL agents, *CELL-mediated cytotoxicity, *IMMUNOPRECIPITATION, *THERAPEUTICS
Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is a Gammaherpesvirus that causes acute infection and establishes life-long latency. KSHV causes several human cancers, including Kaposi's sarcoma, an acquired immune deficiency syndrome (AIDS)-related form of non-Hodgkin lymphoma. Genipin, an aglycone derived from geniposide found in Gardenia jasminoides, is known to be an excellent natural cross-linker, strong apoptosis inducer, and antiviral agent. Although evidence suggests antiviral activity of genipin in several in vitro viral infection systems, no inhibitory effect of genipin on KSHV infection has been reported. Thus, our aim was to determine, using the iSLK-BAC16 KSHV infection system, whether genipin has inhibitory effects on KSHV infection. For this purpose, we evaluated biological effects of genipin on KSHV infection and finally determined the underlying mechanisms responsible for the bioactive effects of genipin. A cytotoxicity assay revealed that genipin caused 50% cytotoxicity at 49.5 μM in iSLK-puro (KSHV-negative) cells and at 72.5 μM in iSLK-BAC16 (KSHV-positive) cells. Caspase 3/7 activities were slightly suppressed by genipin treatment in iSLK-BAC16 cells while significantly induced in iSLK-puro cells. Production of the KSHV latency-associated nuclear antigen (LANA), but not that of the R-transactivator (RTA) protein, was significantly induced by genipin treatment at lower concentration. Consistent with the LANA upregulation, KSHV LANA transcripts, but not RTA transcripts, were expressed at a higher level. Furthermore, KSHV intracellular copy numbers were slightly increased at lower concentration of genipin, while KSHV extracellular copy numbers were significantly increased at higher concentration of genipin. Interestingly, genipin treatment at a lower concentration did induce the expression of DNA (cytosine-5)-methyltransferase 1 (DNMT1); however, a co-immunoprecipitation assay showed that the DNMT1 and LANA induced by genipin did not co-precipitate from iSLK-BAC16 cells. Moreover, a chromatin immunoprecipitation assay demonstrated that genipin treatment enhanced the binding of CCCTC-binding factor (CTCF) to the CTCF-binding site in the KSHV latency control region but suppressed the binding of structural maintenance of chromosomes protein 3 (SMC3) to this site. Genipin treatment also led to the recruitment of additional RNA polymerase to the majority of binding sites of some interesting proteins in the KSHV latency control region, which might be related to the extension of S phase in iSLK-BAC16 cells by genipin treatment. Finally, genipin treatment at lower concentration could promote the KSHV latent replication. In contrast, the treatment at higher concentration could induce the KSHV lytic replication. In conclusion, genipin was shown to be an interesting reagent, which we used to manipulate KSHV life cycle in KSHV latently infected cells. [ABSTRACT FROM AUTHOR]

Published
2016
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136. Tristetraprolin regulates expression of VEGF and tumorigenesis in human colon cancer

Author

Lee, Hyun Hee, primary, Son, Young Joon, additional, Lee, Won Hyeok, additional, Park, Young Woo, additional, Chae, Seoung Wan, additional, Cho, Wha Ja, additional, Kim, Young Min, additional, Choi, Hye‐Jeong, additional, Choi, Dae Hwa, additional, Jung, Seok Won, additional, Min, Young Joo, additional, Park, Soon Eun, additional, Lee, Byung Ju, additional, Cha, Hee Jeong, additional, and Park, Jeong Woo, additional

Published
2009
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148. Detecting Trapdoors in Smart Cards Using Timing and Power Analysis.

Author

Khendek, Ferhat, Dssouli, Rachida, Lee, Jung Youp, Jung, Seok Won, and Lim, Jongin

Abstract

For economic reasons, in spite of security problems, the commands of re-initializing the card and writing patch code are widely used in smart cards. The current software tester has difficulty in detecting these trapdoor commands by reason that trapdoors are not published and programmed sophisticatedly. Up to now the effective way to detect them is to completely reveal and analyze the entire code of the COS with applications such as the ITSEC. It is, however, very time-consuming and expensive processes. We propose a new approach of detecting trapdoors in smart cards using timing and power analysis. By experiments, this paper shows that this approach is a more practical method than the current methods. Keywords: Smart Card, Trapdoor, Timing Analysis, Power Analysis [ABSTRACT FROM AUTHOR]

Published
2005
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149. Safety and efficacy of dietary supplement (gintonin-enriched fraction from ginseng) in subjective memory impairment: A randomized placebo-controlled trial

Author

Lee, Woo-Jin, Shin, Yong-Won, Chang, Hyeyeon, Shin, Hye-Rim, Kim, Won-Woo, Jung, Seok-Won, Kim, Manho, and Nah, Seung-Yeol

Abstract

Gintonin inhibits β-amyloid production, increases acetylcholine level in the brain, and promotes neurogenesis. We evaluated the efficacy of gintonin-enriched fraction (GEF) in improving the cognitive performance in subjective memory impairment.

Published
2022
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150. HBV Dna Level at 24 Weeks is the Best Predictor of Virological Response to Adefovir Add-On Therapy in Patients with Lamivudine Resistance

Author

Shin, Jung Woo, Jung, Seok Won, Park, Bo Ryung, Kim, Chang Jae, Eum, Jun Bum, Kim, Byung Gyu, Jeong, In Du, Bang, Sung-Jo, and Park, Neung Hwa

Abstract

Background The aim of this study was to investigate the relationship between HBV DNA levels at baseline and on-treatment and the virological response at 96 weeks after adefovir add-on therapy in chronic hepatitis B (CHB) patients with lamivudine resistance.Methods Lamivudine and adefovir combination therapy was administered to 122 CHB patients for >24 months.Results Virological response (HBV DNA negativity) was achieved in 53 (43.3%) and 62 patients (50.8%) at 48 and 96 weeks, respectively. The receiver operating characteristic curve analysis showed that the HBV DNA level at week 24 had a greater power (area under the receiver operating characteristic curve 0.978; 95% CI 0.949, 1.000; P<0.001) to predict the virological response at week 96 of treatment than did the pre-treatment HBV DNA level (area under the receiver operating characteristic curve 0.771; 95% CI 0.640, 0.902; P<0.001). The best cutoff value for the HBV DNA level, at week 24, for the prediction of the virological response at week 96 was 200 IU/ ml (3 log10copies/ml), with a sensitivity and specificity of 90.3% and 95.0%, respectively. Using this time frame and cutoff value, 56 (90.3%) out of 62 patients that had a virological response at 96 weeks had <200 IU/ml HBV DNA at 24 weeks.Conclusions Although the HBV DNA level at baseline is often used to predict the antiviral potency of lamivudine and adefovir combination treatment in CHB patients with lamivudine resistance, the results of this study suggest that the HBV DNA level at 24 weeks is a better marker for the virological response.

Published
2012
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