Limited antitumor effect of everolimus in an in vitro Hepg2 cell line study

Eunyoung Tak,Shin Hwang,Dae-Young Jun,Gi-Won Song,Sung-Gyu Lee 한국간담췌외과학회 2016 한국간담췌외과학회 학술대회지 Vol.2016 No.4

Apoptosis of Hepatitis B Virus-expressing Liver Tumor Cells Induced by a High Concentration of Nucleos(t)ide Analogue

TAK, EUNYOUNG,HWANG, SHIN,LEE, HAN CHU,KO, GI-YOUNG,AHN, CHUL-SOO,YOON, YOUNG-IN,LIM, YOUNG-SUK,JUN, DAE-YOUNG,KIM, KI-HUN,SONG, GI-WON,MOON, DEOG-BOK,RYOO, BAEK-YEOL,KIM, NAYOUNG,LEE, SUNG-GYU Potamitis Press 2016 Anticancer research Vol.36 No.11

<P>Background/Aim: We investigated the expression of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and HBV X protein (HBx) in human hepatocellular carcinoma (HCC) and evaluated the effect of high-concentration nucleos(t)ide analogs (NUCs) on liver tumor cell lines. Materials and Methods: This study consisted of three parts: part I used human blood and non-tumor liver tissues; part II used human HCC and adjacent liver tissues; and part III used an HBV-expressing liver tumor cell line. Results: There were close correlations among blood and liver HBV DNA and liver cccDNA. HBV cccDNA and HBx were highly up-regulated in HCC compared to adjacent liver tissues despite NUC therapy. HBV cccDNA and HBx were highly up-regulated in the cccDNA-expressing HepG2.2.15 cell line. Their expression was down-regulated and apoptosis was induced by a very high concentration of NUCs in dose-and time-dependent manner. Conclusion: Very high concentrations of NUCs may have a novel potential to kill replicating HBV-expressing liver tumor cells.</P>

Human carbonyl reductase 1 upregulated by hypoxia renders resistance to apoptosis in hepatocellular carcinoma cells

Tak, Eunyoung,Lee, Seonmin,Lee, Jisun,Rashid, M.A.,Kim, Youn Wha,Park, Jae-Hoon,Park, Won Sang,Shokat, Kevan M.,Ha, Joohun,Kim, Sung Soo Elsevier 2011 Journal of hepatology Vol.54 No.2

<P><B>Background & Aims</B></P><P>Human carbonyl reductase1 (CBR1) has been reported to protect cells against lipid peroxidation. Since human hepatocellular carcinoma (HCC) cells are under oxidative stress in hypoxic conditions, we tested if CBR1 is upregulated by hypoxia inducible factor (HIF)-1α, helps tumor growth under hypoxia, and renders chemoresistance to cisplatin and doxorubicin in HCC.</P><P><B>Methods</B></P><P>Luciferase, EMSA, and chromatin immunoprecipitation (ChIP) assays were performed to analyze whether HIF-1α transactivates CBR1 promoter. CBR1 overexpression, siRNA, and inhibitors were used to study the role of CBR1 in tumor survival under hypoxia and chemoresistance to cisplatin and doxorubicin in HCC. FACS and Western blot analysis for oxidative stress markers were performed to measure ROS. Immunohistochemistry (IHC) was performed to analyze CBR1 expression in 78 cases of HCC and 123 cases of colon cancer tissues.</P><P><B>Results</B></P><P>The <I>CBR1</I> promoter was activated by HIF-1α. CBR1 overexpression enhanced cell survival by decreasing oxidative stress under hypoxia, cisplatin, and doxorubicin treatment. <I>CBR1</I>-siRNA increased apoptosis via increasing oxidative stress. Combinational therapy of CBR1 inhibitors with cisplatin or doxorubicin enhanced cell death in HCC cells. IHC showed CBR1 overexpression in 56 (72%) out of 78 HCC and 88 (72%) out of 123 colon cancer cases.</P><P><B>Conclusions</B></P><P>Overexpressed CBR1 by HIF-1α plays important roles in tumor growth under hypoxia and chemoresistance to anticancer drugs. The inhibition of CBR1 by specific inhibitors enhances anticancer drug efficacy in HCC. Therefore, we concluded that CBR1 is a good molecular target for the development of anticancer drugs for HCC patients.</P>

Predictors of Alcohol Use in Korean Adolescents

Eunyoung Lee,Youngran Tak 한국간호과학회 2005 한국간호과학회 학술대회 Vol.2005 No.10

Peer and Parental Influences on Adolescent Smoking

Eunyoung Lee,Youngran Tak 한국간호과학회 2005 Journal of Korean Academy of Nursing Vol.35 No.4

The Incidence of Cardiovascular Events Is Comparable Between Normoalbuminuric and Albuminuric Diabetic Patients With Chronic Kidney Disease

Lee, Eunyoung,Oh, Hyung Jung,Park, Jung Tak,Han, Seung Hyeok,Ryu, Dong-Ryeol,Kang, Shin-Wook,Yoo, Tae-Hyun Wolters Kluwer Health 2016 Medicine Vol.95 No.15

<P><B>Abstract</B></P><P>Diabetic kidney disease leads to microalbuminuria and gradually progresses to overt proteinuria with renal insufficiency. Recent studies have demonstrated that 20% to 40% of patients with diabetic kidney disease are normo- to microalbuminuric, despite reduced renal function. We investigated renal and cardiovascular outcomes in patients with diabetes and renal insufficiency who were normo-, micro-, and macroalbuminuric.</P><P>Patients with diabetes and stage III or IV chronic kidney disease were recruited and divided into normoalbuminuric, microalbuminuric, and macroalbuminuric groups. New-onset cardiovascular events and renal outcomes, defined by end-stage renal disease or a 50% decline in estimated glomerular filtration rate, were evaluated.</P><P>Among the 1136 study patients, 255 (22.4%) were normoalbuminuric. During a mean follow-up duration of 44 months, the incidence of cardiovascular disease was similar among groups (<I>P</I> = 0.68). However, renal outcomes were significantly more common in patients with macroalbuminuria than in those who were normoalbuminuric or microalbuminuric (<I>P</I> < 0.001). Multivariate Cox analysis identified macroalbuminuria and estimated glomerular filtration rate as independent predictors of renal outcomes. The amount of albuminuria was not associated with cardiovascular events in this population.</P><P>Although cardiovascular events were similar in patients with diabetic kidney disease and renal insufficiency, renal outcomes differed significantly according to the amount of albuminuria.</P>

Peer and Parental Influences on Adolescent Smoking

Lee Eunyoung,Tak Youngran Korean Society of Nursing Science 2005 Journal of Korean Academy of Nursing Vol.35 No.4

Purpose. The purpose of this study was to determine the relationship between peer and parental factors and smoking behavior of adolescents in urban cities and to investigate whether there are gender differences. Methods. A stratified and random cluster sampling design was used to obtain a cross-sectional sample of high school students in two urban cities. The sample consisted of 512 Korean adolescents (256 boys and 256 girls) aged 15 to 18 (mean age 16.7$\pm$.58). Self-reported questionnaire consisted of adolescent smoking behavior, peer smoking and alcohol use, parental smoking and alcohol use, father-mother-peer relationships and perceived social support from peers and parents. Multiple logistic regression analysis was used to examine the hypothesized model. Results. The findings showed that peer and parental factors accounted for $30.3\%$ of the variance in adolescent smoking and peer smoking was most strongly associated with adolescent smoking behavior (OR = 10.18). In addition, peer smoking (OR = 4.71), peer alcohol use (OR = 4.21), and peer relationships (OR = 1.03) were significantly associated with boys' smoking behavior. In girls, peer smoking (OR = 26.50) and parent smoking (OR = 5.48) were significantly associated with smoking behavior. Conclusions. Consistent with previous findings, peer smoking is a significant factor on adolescent smoking. Specifically, boys would be more influenced from peers than girls. Therefore, smoking prevention programs for adolescents might be focused on the social context such as, resisting to peer pressure and enhancing the self-efficacy to control.

A multifunctional composite of an antibacterial higher-valent silver metallopharmaceutical and a potent wound healing polypeptide: a combined killing and healing approach to wound care

Pal, Sukdeb,Tak, Yu Kyung,Han, Eunyoung,Rangasamy, Sabarinathan,Song, Joon Myong The Royal Society of Chemistry 2014 NEW JOURNAL OF CHEMISTRY Vol.38 No.8

<P>The present study relates to a combined killing and healing approach for the treatment of infected wounds. Herein we report a multifunctional, including antimicrobial and wound healing, composite containing a conjugate of a bi-valent silver polydiguanide that demonstrated high antibacterial activity <I>in vitro</I> and a potent wound healing polypeptide, histatin-1, for the treatment of infected wounds. The synthesis of silver(<SMALL>II</SMALL>) chlorhexidine [Ag(<SMALL>II</SMALL>)CHX] was accomplished by the oxidation of Ag(<SMALL>I</SMALL>), followed by the complexation of the oxidized metal with chlorhexidine (CHX), whereas the metal complex conjugate of the solid phase-synthesized histatin polypeptide (Hst-1), Hst-1-[Ag(<SMALL>II</SMALL>)CHX], was realized by mixing the starting materials in aqueous solution. The change in the Hst-1 structure upon binding with the silver complex was examined by circular dichroism spectroscopy. The wound healing applicability of the histatin polypeptide and its metal complex conjugate was tested using the synthesized Hst-1 and Hst-1-[Ag(<SMALL>II</SMALL>)CHX] complex on 3T3-L1 preadipocytes in a cell-spreading assay. The antibacterial activity of the silver metal complex and its Hst-1 conjugate was tested against several gram positive and gram negative bacteria, including Methicillin-resistant <I>Staphylococcus aureus</I> (MRSA) and Methicillin-resistant coagulase negative <I>staphylococcus</I> (MRCNS) by a broth microdilution method. The results of these experiments revealed that the polypeptide and silver(<SMALL>II</SMALL>) polydiguanide complex retained their individual wound healing and antimicrobial activity even in their conjugate. The conjugate of an antibacterial higher-valent silver polydiguanide complex with a potent wound healing polypeptide (Hst-1) showed promise as a new multifunctional therapeutic wherein the killing and healing functions of the constituent materials are preserved together for the development of new-generation wound-care agents.</P> <P>Graphic Abstract</P><P>A histatin-1 and silver(<SMALL>II</SMALL>) polydiguanide complex composite demonstrated both antibacterial and wound healing promoting activity. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c4nj00160e'> </P>

Synergistic effect of metformin on sorafenib in in vitro study using hepatocellular carcinoma cell lines

Yong-Gyu Chung,Eunyoung Tak,Shin Hwang,Joo-Young Lee,Ji-Ye Kim,Ye-Young Kim,Gi-Won Song,Kyoung-Jin Lee,Nayoung Kim 한국간담췌외과학회 2018 Annals of hepato-biliary-pancreatic surgery Vol.22 No.3

Backgrounds/Aims: Hepatocellular carcinoma (HCC) recurrence remains a great concern following hepatic resection and liver transplantation. We investigated the metformin-induced cytotoxic effects on sorafenib in an in vitro study using HCC cell lines. Methods: This research was conducted through an in vitro study using one HepG2.2.15 liver tumor and two patient-derived graft HCC cell lines. Results: An in vitro study revealed noticeable cytotoxic effects of metformin as well as noticeable synergistic cytotoxic effects of metformin and sorafenib on cell viability. Assays for the mechanisms of action of antitumor effects revealed that alpha-fetoprotein expression was suppressed by both metformin and sorafenib, but no synergistic effect was observed. LC3-I and LC3-II assays revealed the synergistic upregulation of autophagy and assays for IL-1, IL-6, p53, and TNF- revealed the synergistic upregulation of cell damage and apoptosis. In contrast, metformin did not affect HBx expression, thus no noticeable synergistic effect was considered to be present. Conclusions: Our in vitro study demonstrated cytotoxic effects of metformin and synergistic antitumor effects of sorafenib. These results should be verified in further clinical studies with patients of advanced HCC.

Knock‐Down of Argonaute 2 (AGO2) Induces Apoptosis in Myeloid Leukaemia Cells and Inhibits siRNA‐Mediated Silencing of Transfected Oncogenes in HEK‐293 Cells

Naoghare, Pravin K.,Tak, Yu Kyung,Kim, Min Jung,Han, Eunyoung,Song, Joon Myong Blackwell Publishing Ltd 2011 Basic & Clinical Pharmacology & Toxicology Vol.109 No.4

<P><B>Abstract: </B> Understanding the role of oncomirs allows new insights into the development of modern therapeutic approaches for the repression of multiple oncomirs in cancer cells. At present, no suitable approach is available to repress the development of multiple oncomirs in cancer cells. Herein, we report that argonaute 2 (AGO2) could be a unique molecule to regulate the development of multiple oncomirs in cancer cells. Knock‐down of AGO2 by custom‐made AGO2 siRNA resulted in the induction of apoptosis in myeloid leukaemia cells (HL‐60). Further investigations revealed that knock‐down of AGO2 by custom‐made AGO2 siRNA in HEK‐293 cells resulted in silencing of the expression of target genes vascular endothelial growth factor A and histone deacetylase 2, which are known to be involved in the development of myeloid leukaemia. From these results, it can be predicted that AGO2 could regulate siRNA‐mediated RNAi pathways in cancer cells. Furthermore, we investigated the possible implication of AGO2 in drug‐induced apoptosis. Investigations revealed that treatment with the newly synthesized drug analogue SH‐03[{(7S,7aR,13aS)‐9,10‐dimethoxy‐3,3‐dimethyl‐7,7a,13,13atetrahydro‐3H‐chromeno[3,4‐b]pyrano[2,3‐h]chromen‐7‐ol}] could induce AGO2‐mediated apoptosis in myeloid leukaemia cells via intrinsic apoptotic pathways independent of Dicer.</P>