Original Articles : Effect of aldosterone on the amplification of oncolytic vaccinia virus in human cancer Lines

( Hyun Ju Lee ),( Ja Sung Rho ),( Shao Ran Gui ),( Mi Kyung Kim ),( Yu Kyoung Lee ),( Yeon Sook Lee ),( Jeong Eun Kim ),( Eu Na Cho ),( Mong Cho ),( Tae Ho Hwang ) 대한간학회 2011 Clinical and Molecular Hepatology(대한간학회지) Vol.17 No.3

Background/Aims: JX-594 is an oncolytic virus derived from the Wyeth vaccinia strain that causes replication-dependent cytolysis and antitumor immunity. Starting with a cross-examination of clinical-trial samples from advanced hepatocellular carcinoma patients having high levels of aldosterone and virus amplification in JX-594 treatment, we investigated the association between virus amplification and aldosterone in human cancer cell lines. Methods: Cell proliferation was determined by a cell-counting-kit-based colorimetric assay, and vaccinia virus quantitation was performed by quantitative polymerase chain reaction (qPCR) and a viral plaque assay. Also, the intracellular pH was measured using a pH-sensitive dye. Results: Simultaneous treatment with JX-594 and aldosterone significantly increased viral replication in A2780, PC-3, and HepG2 cell lines, but not in U2OS cell lines. Furthermore, the aldosterone treatment time altered the JX-594 replication according to the cell line. The JX-594 replication peaked after 48 and 24 hours of treatment in PC-3 and HepG2 cells, respectively. qPCR showed that JX-594 entry across the plasma membrane was increased, however, the changes are not significant by the treatment. This was inhibited by treatment with spironolactone (an aldosterone-receptor inhibitor). JX-594 entry was significantly decreased by treatment with EIPA [5-(N-ethyl-N-isopropyl)amiloride; a Na+/H+-exchange inhibitor], but aldosterone significantly restored JX-594 entry even in the presence of EIPA. Intracellular alkalization was observed after aldosterone treatment but was acidified by EIPA treatment. Conclusions: Aldosterone stimulates JX-594 amplification via increased virus entry by affecting the H+ gradient. (Korean J Hepatol 2011;17:213-219)

Cell death induction and intracellular vesicle formation in human colorectal cancer cells treated with Δ9-Tetrahydrocannabinol

Hwang Yu-Na,Kwon In-Seo,Park Ju-Hee,Na Han-Heom,Kwon Tae-Hyung,Park Jin-Sung,Kim Keun-Cheol 한국유전학회 2023 Genes & Genomics Vol.45 No.12

Background Δ9-Tetrahydrocannabinol (Δ9-THC) is a principal psychoactive extract of Cannabis sativa and has been traditionally used as palliative medicine for neuropathic pain. Cannabidiol (CBD), an extract of hemp species, has recently attracted increased attention as a cancer treatment, but Δ9-THC is also requiring explored pharmacological application. Objective This study evaluated the pharmacological effects of Δ9-THC in two human colorectal cancer cell lines. We investigated whether Δ9-THC treatment induces cell death in human colorectal cancer cells. Methods We performed an MTT assay to determine the pharmacological concentration of Δ9-THC. Annxein V and Western blot analysis confirmed that Δ9-THC induced apoptosis in colorectal cancer cells. Metabolic activity was evaluated using MitoTracker staining and ATP determination. We investigated vesicle formation by Δ9-THC treatment using GW9662, known as a PPARγ inhibitor. Results The MTT assay showed that treatment with 40 μM Δ9-THC and above inhibited the proliferation of colorectal cancer cells. Multiple intracytoplasmic vesicles were detected upon microscopic observation, and fluorescence-activated cell sorting analysis showed cell death via G1 arrest. Δ9-THC treatment increased the expression of cell death marker proteins, including p53, cleaved PARP-1, RIP1, and RIP3, suggesting that Δ9-THC induced the death of colorectal cancer cells. Δ9-THC treatment also reduced ATP production via changes in Bax and Bcl-2. Δ9-THC regulated intracytoplasmic vesicle formation by modulating the expression of PPARγ and clathrin, adding that antiproliferative activity of Δ9-THC was also affected. Conclusion In conclusion, Δ9-THC regulated two functional mechanisms, intracellular vesicle formation and cell death. These findings can help to determine how cannabinoids can be used most effectively to improve the efficacy of cancer treatment.

Dual Cytotoxic Responses Induced by Treatment of A549 Human Lung Cancer Cells with Sweet Bee Venom in a Dose-Dependent Manner

Yu-Na Hwang,In-Seo Kwon,나한흠,박진성,김근철 대한약침학회 2022 Journal of pharmacopuncture Vol.25 No.4

Objectives: Sweet bee venom (sBV) is purified from Apis mellifera, containing a high level of melittin—its main component. It has been used as a therapeutic agent for pain relief and anti-inflammation, as well as for treating neuronal abnormalities. Recently, there have been studies on the therapeutic application of sBV for anticancer treatment. In the present study, we investigated the pharmacological effect of sBV treatment in A549 human lung cancer cells. Methods: We used microscopic analysis to observe the morphological changes in A549 cells after sBV treatment. The MTT assay was used to examine the cytotoxic effect after dose-dependent sBV treatment. Molecular changes in sBV were evaluated by the expression of apoptosis marker proteins using western blot analysis. Results: Microscopic analysis suggested that the growth inhibitory effect occurred in a dose-dependent manner; however, cell lysis occurred at a concentration over 20 μg/mL of sBV. The MTT assay indicated that sBV treatment exhibited a growth inhibitory effect at a concentration over 5 μg/mL. On fluorescence activated cell sorting analysis, G0 dead cells were observed after G1 arrest at treatment concentrations up to 10 μg/mL. However, rapid cell rupture was observed at a concentration of 20 μg/mL. Western blot analysis demonstrated that sBV treatment modulated the expression of multiple cell death-related proteins, including cleaved-PARP, cleaved-caspase 9, p53, Bcl2, and Bax. Conclusion: sBV induced cell death in A549 human lung cancer cells at a pharmacological concentration, albeit causing hemolytic cell death at a high concentration.

Detection of Nosema ceranae from Bombus terrestris via Quantitative Real-Time PCR

Na Rae Choi,Yun Jeong Hwang,Young Bin Jeon,Yu Ni Seo,Chuleui Chung,Dae-Weon Lee 한국응용곤충학회 2013 한국응용곤충학회 학술대회논문집 Vol.2013 No.10

The bumblebee, Bombus terrestris, has played an important role as one of the alternative pollinators since the outbreak of honeybee collapse disorder. Recently, pathogens and parasites such as viruses, bacteria and mites, which affect the life span and fecundity of their host, have been discovered in B. terristris. In order to detect the microsporidian pathogen, Nosema Spp. in the field populations of B. terristris, we collected adults and isolated their genomic DNA for diagnostic PCR. The PCR primers specific for Nosema Spp. were newly designed and applied to gene amplification for cloning. Only small subunit ribosomal RNA(SSU rRNA) gene of N. ceranae was successfully amplified and sequenced among examined genes, which indicates that N. ceranae mainly infects the examined field population of B. terristris. To detect of SSU rRNA gene, two regions of SSU rRNA gene were selected by primary PCR analysis and further analyzed in quantitative real-time PCR(qRT-PCR). The qRT-PCR analysis demonstrated that SSU rRNA of N. ceranae was detected at concentrations as low as 0.85 ng/μl genomic DNA. This result suggests that the detection via qRT-PCR can be applied for the rapid and sensitive diagnosis of N. ceranae infection in the field population as well as risk assessment of B. terristris.

MHY451 induces cell cycle arrest and apoptosis by ROS generation in HCT116 human colorectal cancer cells

Hwang, Na Lam,Kang, Yong Jung,Sung, Bokyung,Hwang, Seong Yeon,Jang, Jung Yoon,Oh, Hye Jin,Ahn, Yu Ra,Kim, Do Hyun,Kim, Su Jeong,Ullah, Sultan,Hossain, Mohammad Akbar,Moon, Hyung Ryong,Chung, Hae Young Spandidos Publications 2017 Oncology Reports Vol.38 No.3

<P>Colorectal cancer (CRC) is the third most frequently diagnosed cancer and cause of cancer-related deaths. Despite advancements in conventional therapeutic approaches to CRC, most patients with CRC die of their disease. There is a need to develop novel therapeutic agents for this malignancy. Therefore, the present study aimed to examine the anticancer effects and elucidate the underlying mechanism of MHY451 in HCT116 human colorectal cancer cells. Treatment with MHY451 inhibited cell growth in a time- and concentration-dependent manner. MHY451 increased the accumulation of cell cycle progression at the G2/M phase. This agent decreased the protein level of cyclin B1 and its activating partners, Cdc25c and Cdc2, whereas it increased the cell cycle inhibitor p21WAF/CIP. The induction of apoptosis was observed by decreased viability, cleavage of poly(ADP-ribose) polymerase (PARP), alteration in the ratio of Bax/Bcl-2 protein expression and reduction of procaspase-8 and -9. Pretreatment with Z-VAD-FMK, a pan-caspase inhibitor, inhibited MHY451-induced apoptosis, indicating that apoptotic cell death by MHY451 was mediated through caspases. Moreover, the apoptotic effect of MHY451 was reactive oxygen species (ROS)-dependent, evidenced by the inhibition of MHY451-induced PARP cleavage and ROS generation by N-acetylcysteine-induced ROS scavenging. Taken together, these results demonstrate that MHY451 exerts anticancer effects by regulating the cell cycle, inducing apoptosis through caspase activation and generating ROS. These results suggest that MHY451 has considerable potential for chemoprevention or treatment of CRC or both.</P>

New-onset of palmoplantar pustulosis while on adalimumab treatment for ankylosing spondylitis

( Yu Na Lee ),( Ho Jung Jung ),( Yu Ri Kim ),( Jae Wook Jung ),( Hyun Jung Park ),( Hyung Jin Hahn ),( Young Ji Hwang ),( Ji Young Kim ),( Yang Won Lee ),( Yong Beom Choe ),( Kyu Joong Ahn ) 대한피부과학회 2012 대한피부과학회 학술발표대회집 Vol.64 No.1

Physical and chemical properties of experimental mixture of mineral trioxide aggregate and glass ionomer cement

Jeong, Yu-Na,Yang, So-Young,Park, Bum-Jun,Park, Yeong-Joon,Hwang, Yun-Chan,Hwang, In-Nam,Oh, Won-Mann 大韓齒科保存學會 2010 Restorative Dentistry & Endodontics Vol.35 No.5

Objectives: The purpose of this study was to determine the setting time, compressive strength, solubility, and pH of mineral trioxide aggregate (MTA) mixed with glass ionomer cement (GIC) and to compare these properties with those of MTA, GIC, IRM, and SuperEBA. Materials and Methods: Setting time, compressive strength, and solubility were determined according to the ISO 9917 or 6876 method. The pH of the test materials was determined using a pH meter with specified electrode for solid specimen. Results: The setting time of MTA mixed with GIC was significantly shorter than that of MTA. Compressive strength of MTA mixed with GIC was significantly lower than that of other materials at all time points for 7 days. Solubility of 1 : 1 and 2 : 1 specimen from MTA mixed with GIC was significantly higher than that of other materials. Solubility of 1 : 2 specimen was similar to that of MTA. The pH of MTA mixed with GIC was 2-4 immediately after mixing and increased to 5-7 after 1 day. Conclusions: The setting time of MTA mixed with GIC was improved compared with MTA. However, other properties such as compressive strength and pH proved to be inferior to those of MTA. To be clinically feasible, further investigation is necessary to find the proper mixing ratio in order to improve the drawbacks of MTA without impairing the pre-existing advantages and to assess the biocompatibility. 연구목적: 본 연구의 목적은 glass ionomer cement (GIC)와 혼합한 mineral trioxide aggregate (MTA)의 경화 시간, 압축 강도, 용해도, pH를 평가하고 이것을 MTA, GIC, IRM, SuperEBA와 비교하는 것이다. 연구 재료 및 방법: 경화 시간과 압축 강도는 ISO 9917, 그리고 용해도는 ISO 6876 기준에 따라 측정하였다. pH는 고체시편 전용 전극이 연결된 pH meter를 이용하여 측정하였다. 결과: GIC와 혼합한 MTA의 경화시간은 MTA보다 유의하게 짧았으며 압축 강도는 7일간 모든 시점에서 다른 재료보다 유의하게 낮았다. GIC와 혼합한 MTA 중에서 1 : 1과 2 : 1 시편의 용해도는 다른 실험군보다 유의하게 높았다. 또한 GIC와 혼합한 MTA의 pH는 혼합직후 2-4의 범위에서 1일 후 5-7 사이로 증가하였다. 결론: GIC와 혼합한 MTA의 경화시간은 MTA에 비해 개선되었으나 압축강도 및 pH와 같은 다른 성질들은 MTA에 비해 오히려 열등한 것으로 밝혀졌다. 임상적 사용이 가능하려면, MTA의 기존 장점을 저해하지 않으면서 단점을 개선하기 위한 적절한 혼합비를 찾아내고 생체친화성을 평가하는 추가적인 연구가 필수적이다.

강화되는 총인 방류수 수질기준을 만족하는 친환경 저에너지형 MBR 개발

유하나 ( Ha Na Yu ),나유미 ( Yu Mee Na ),최훈창 ( Hun Chang Choi ),이동진 ( Dong Jin Lee ),윤희성 ( Hee Sung Yoon ),황윤영 ( Yun Young Hwang ),김연국 ( Youn Kook Kim ) 한국물환경학회 ( 구 한국수질보전학회 ) 2012 한국물환경학회·대한상하수도학회 공동 춘계학술발표회 Vol.2012 No.-

A multicenter study of entecavir <i>vs.</i> tenofovir on prognosis of treatment-naïve chronic hepatitis B in South Korea

Kim, Seung Up,Seo, Yeon Seok,Lee, Han Ah,Kim, Mi Na,Lee, Yu Rim,Lee, Hye Won,Park, Jun Yong,Kim, Do Young,Ahn, Sang Hoon,Han, Kwang-Hyub,Hwang, Seong Gyu,Rim, Kyu Sung,Um, Soon Ho,Tak, Won Young,Kweon Elsevier 2019 Journal of hepatology Vol.71 No.3

<P><B>Background & Aims</B></P> <P>It is currently unclear which antiviral agent, entecavir (ETV) or tenofovir disoproxil fumarate (TDF), is superior for improving prognosis in patients with chronic hepatitis B (CHB). Here, we assessed the ability of these 2 antivirals to prevent liver-disease progression in treatment-naïve patients with CHB.</P> <P><B>Methods</B></P> <P>From 2012 to 2014, treatment-naïve patients with CHB who received ETV or TDF as a first-line antiviral agent were recruited from 4 academic teaching hospitals. Patients with decompensated cirrhosis or hepatocellular carcinoma (HCC) at enrollment were excluded. Cumulative probabilities of HCC and death or orthotopic liver transplant (OLT) were assessed.</P> <P><B>Results</B></P> <P>In total, 2,897 patients (1,484 and 1,413 in the ETV and TDF groups, respectively) were recruited. The annual HCC incidence was not statistically different between the ETV and TDF groups (1.92 <I>vs</I>. 1.69 per 100 person-years [PY], respectively; adjusted hazard ratio [HR] 0.975 [<I>p</I> = 0.852] by multivariate analysis). Propensity score (PS)-matched and inverse probability of treatment weighting (ITPW) analyses yielded similar patterns of results (HR 1.021 [<I>p</I> = 0.884] and 0.998 [<I>p</I> = 0.988], respectively). The annual incidence of death or OLT was not statistically different between the ETV and TDF groups (0.52 <I>vs</I>. 0.53 per 100 PY, respectively; adjusted HR 1.202 [<I>p</I> = 0.451]). PS-matched and ITPW analyses yielded similar patterns of results (HR 1.248 [<I>p</I> = 0.385] and 1.239 [<I>p</I> = 0.360], respectively). These findings were consistently reproduced in patients with compensated cirrhosis (all <I>p</I> >0.05).</P> <P><B>Conclusions</B></P> <P>The overall prognosis in terms of HCC and death or OLT was not statistically different between the ETV and TDF groups. Further studies are needed to validate our results.</P> <P><B>Lay summary</B></P> <P>It is currently unclear which antiviral agent, entecavir or tenofovir disoproxil fumarate, is superior for improving prognosis in patients with chronic hepatitis B virus infection. In this analysis we found that there was no difference in terms of overall prognosis, including risk of hepatocellular carcinoma, death, or the need for a liver transplant, in patients receiving either antiviral.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The hepatocellular carcinoma risk was not statistically different between the ETV and TDF groups. </LI> <LI> The death or liver transplant risk was not statistically different between the 2 groups. </LI> <LI> These results were consistently reproduced after adjusting for confounding variables. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

The prognosis of patients less than 40 years with bladder cancer.

Na, Seong Woong,Yu, Seong Hyeon,Kim, Kwang Ho,Hwang, Eu Chang,Jung, Seung Il,Kwon, Dong Deuk,Kang, Taek Won Medknow Publications 2014 Journal of cancer research and therapeutics Vol.10 No.3

<P>Natural history of young patients with bladder cancer has not yet been known. So this study aimed to understand characteristics and prognosis of patients less than 40 years with bladder cancer.</P>