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      • Acute disseminated encephalomyelitis caused by Epstein-Barr virus infection in an immunocompetent adult woman

        Oh, Hyunjoo,Yoo, Jeong Rae,Heo, SangTaek,Oh, Jung-Hwan,Lee, Ho Kyu Institute for Medical Science 2019 The Journal of Medicine and Life Science Vol.16 No.1

        Epstein-Barr virus(EBV) infection is common and usually asymptomatic in young infants and children. However, EBV infections in transplant recipients and other immunosuppressed patients can be fatal. EBV-related neurological complications in immunocompetent adults are extremely rare and self-limited. Acute disseminated encephalomyelitis(ADEM) may also follow EBV infection; ADEM is characterized by abrupt onset and rapid progression. We report an immunocompetent adult patient who developed diffuse meningoencephalitis with ADEM-like features caused by EBV infection. A 35-year-old Vietnamese woman was admitted presenting with urinary retention, altered mental status, and paraplegia. PCR of the patient's cerebrospinal fluid showed positive results for EBV. Brain and spine magnetic resonance imaging showed ADEM-like features. She was treated with acyclovir, steroid, and immunoglobulins. We report the case of an immunocompetent adult Vietnamese woman who presented with rapidly progressive diffuse meningoencephalitis associated with EBV infection and was treated with antivirals, corticosteroids, and immunoglobulins.

      • Identification of an evolutionarily conserved, functional noncoding element regulated by Six1 homeoprotein

        Jeong, Yongsu,Oh, Sangtaek The Genetics Society of Japan 2010 Genes & genetic systems Vol.85 No.3

        <P>Six1, which belongs to the <I>sine oculis</I> homeobox (<I>Six</I>) protein family, is an evolutionarily conserved transcription factor found in diverse organisms ranging from flatworms to humans. <I>Six1</I> is expressed in various tissues including the nervous system during ontogenesis and has been implicated in cell differentiation, morphogenesis, and organogenesis of the ganglia and sensory placodes. However, the molecular mechanisms by which Six1 influences these events at the transcriptional level remain largely unknown. In this study, we used ChIP-Display to discover genomic regions occupied <I>in vivo</I> by Six1 homeoprotein in the developing mouse embryo. To validate Six1 occupancy at each of Six1-bound regions, ChIP - Quantitative PCR was performed using locus-specific primers, and it showed robust enrichment of the Six1-bound sequences. To address their regulatory potential, each of the Six1-bound sequences was cloned into a reporter cassette containing beta-globin minimal promoter and <I>lacZ</I> gene and assayed for enhancer activity in transgenic mouse embryos. One of the novel sequences, which was designated Six1-bound Regulatory Element 1 (SRE1), was sufficient to activate <I>lacZ</I> reporter expression in the cranial and spinal ganglia. Comparative genomic analysis identified SRE1 sequences from a number of vertebrate phyla. Transgenic embryos carrying SRE1 sequences from human, chicken and frog showed reporter expression in a pattern similar to that of mouse SRE1, indicating their functional conservation. Through mutational analysis, we further showed that a conserved binding site matching the consensus for Six1/2/4/5 is required for the SRE1 regulatory activity. These data suggest that SRE1 is a functionally conserved transcriptional enhancer regulated by Six1.</P>

      • KCI등재SCISCIE
      • SCISCIESCOPUS

        CGK062, a small chemical molecule, inhibits cancer upregulated gene 2-induced oncogenesis through NEK2 and β-catenin

        Kaowinn, Sirichat,Oh, Sangtaek,Moon, Jeong,Yoo, Ah Young,Kang, Ho Young,Lee, Mi Rim,Kim, Ji Eun,Hwang, Dae Youn,Youn, So Eun,Koh, Sang Seok,Chung, Young-Hwa D.A. Spandidos 2019 International journal of oncology Vol.54 No.4

        <P>The mechanisms through which cancer-upregulated gene 2 (CUG2), a novel oncogene, affects Wnt/β-catenin signaling, essential for tumorigenesis, are unclear. In this study, we aimed to elucidate some of these mechanisms in A549 lung cancer cells. Under the overexpression of CUG2, the protein levels and activity of β-catenin were evaluated by western blot analysis and luciferase assay. To examine a biological consequence of β-catenin under CUG2 overexpression, cell migration, invasion and sphere formation assay were performed. The upregulation of β-catenin induced by CUG2 overexpression was also accessed by xenotransplantation in mice. We first found that CUG2 overexpression increased β-catenin expression and activity. The suppression of β-catenin decreased cancer stem cell (CSC)-like phenotypes, indicating that β-catenin is involved in CUG2-mediated CSC-like phenotypes. Notably, CUG2 overexpression increased the phosphorylation of β-catenin at Ser33/Ser37, which is known to recruit E3 ligase for β-catenin degradation. Moreover, CUG2 interacted with and enhanced the expression and kinase activity of never in mitosis gene A-related kinase 2 (NEK2). Recombinant NEK2 phosphorylated β-catenin at Ser33/Ser37, while NEK2 knockdown decreased the phosphorylation of β-catenin, suggesting that NEK2 is involved in the phosphorylation of β-catenin at Ser33/Ser37. Treatment with CGK062, a small chemical molecule, which promotes the phosphorylation of β-catenin at Ser33/Ser37 through protein kinase C (PKC)α to induce its degradation, reduced β-catenin levels and inhibited the CUG2-induced features of malignant tumors, including increased cell migration, invasion and sphere formation. Furthermore, CGK062 treatment suppressed CUG2-mediated tumor formation in nude mice. Taken together, the findings of this study suggest that CUG2 enhances the phosphorylation of β-catenin at Ser33/Ser37 by activating NEK2, thus stabilizing β-catenin. CGK062 may thus have potential for use as a therapeutic drug against CUG2-overexpressing lung cancer cells.</P>

      • KCI등재

        Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation

        Nam TaeKyung,Kang Wonku,Oh Sangtaek 한국미생물·생명공학회 2023 Journal of microbiology and biotechnology Vol.33 No.9

        Kinetin riboside is a naturally produced cytokinin that displays strong antiproliferative activity in various human cancer cells. However, the mechanism of chemoprevention in colorectal cancer cells has not been elucidated. We used a cell-based reporter system to identify kinetin riboside as an antagonist of the Wnt/β-catenin pathway, which is aberrantly upregulated in colorectal cancer. Kinetin riboside suppressed β-catenin response transcription (CRT) by accelerating the degradation of intracellular β-catenin via a proteasomal degradation pathway. Pharmacological inhibition of glycogen synthase kinase-3β did not affect CRT downregulation. Kinetin riboside decreased the intracellular β-catenin levels in colorectal cancer cells with mutations in adenomatous polyposis coli (APC) and β-catenin. Consistently, kinetin riboside repressed expression of c-Myc and cyclin D1, βcatenin/T-cell factor (TCF)-dependent genes, and inhibited the proliferation of colorectal cancer cells. In addition, kinetin riboside stimulated apoptosis, as measured by an increase in annexin VFITC-stained cells. These findings suggest that kinetin riboside exerts its anti-cancer activity by promoting β-catenin degradation and has significant potential as a chemopreventive agent for colorectal cancer cells.

      • KCI등재후보

        참그물 바탕말 추출물에 의한 Wnt/${\beta}$-Catenin 신호전달체계 저해

        조문주,오상택,Cho, Munju,Oh, Sangtaek 한국해양바이오학회 2006 한국해양바이오학회지 Vol.1 No.4

        Wnt/${\beta}$-catenin 신호전달계의 비정상적인 활성화는 ${\beta}$-catenin response transcription (CRT)를 증가시킬 뿐 아니라 대장암의 발생과 밀접한 관련이 있다. 따라서 Wnt/${\beta}$-catenin 신호전달계는 대장암에 대한 항암제 개발 및 대장암 치료에 중요한 표적이 된다. 본 연구에서는 세포기반 초고속 스크리닝 기법을 사용하여 Wnt/${\beta}$-catenin 신호를 저해하는 참그물 바탕말 추출물을 발굴하였다. 참그물 바탕말 추출물은 세포내 ${\beta}$-catenin 단백질 수준에는 영향을 미치지 않았으며 ${\beta}$-catenin/TCF에 의해 조절되는 유전자 중의 하나인 cyclin D1의 발현을 저해하였다. 또한 참그물 바탕말 추출물은 다양한 대장암의 증식을 저해하였다. 본 연구의 결과들로부터 참그물 바탕말 추출물이 잠재적으로 대장암을 포함하는 새로운 암 예방 및 치료제로 사용될 수 있을 것이다. Abnormal activation of the Wnt/${\beta}$-catenin pathway and subsequent up-regulation of ${\beta}$-catenin response transcription (CRT) are associated with the development of colon cancer. Thus, the Wnt/${\beta}$-catenin pathway is an attractive target for chemoprevention and treatment of this cancer. In this study, we used a cell-based screen to identify a methanol extract of Dictyota dichotoma (EDD) that suppresses the Wnt/${\beta}$-catenin pathway without altering the level of ${\beta}$-catenin protein and reduces the expression of cyclin D1, which is a known ${\beta}$-catenin/T cell factor (TCF)-dependent gene. EDD inhibited the growth of various colon cancer cells. Our findings suggest that EDD can potentially be used as a chemopreventive agent against colon cancer.

      • SCISCIESCOPUS

        Cytotoxic Activity of Rearranged Drimane Meroterpenoids against Colon Cancer Cells via Down-Regulation of β-Catenin Expression

        Hwang, In Hyun,Oh, Joonseok,Zhou, Wei,Park, Seoyoung,Kim, Joo-Hyun,Chittiboyina, Amar G.,Ferreira, Daneel,Song, Gyu Yong,Oh, Sangtaek,Na, MinKyun,Hamann, Mark T. American Chemical Society and American Society of 2015 Journal of natural products Vol.78 No.3

        <P/><P>Colorectal cancer has emerged as a major cause of death in Western countries. Down-regulation of β-catenin expression has been considered a promising approach for cytotoxic drug formulation. Eight 4,9-friedodrimane-type sesquiterpenoids (<B>1</B>–<B>8</B>) were acquired using the oxidative potential of <I>Verongula rigida</I> on bioactive metabolites from two <I>Smenospongia</I> sponges. Compounds <B>3</B> and <B>4</B> contain a 2,2-dimethylbenzo[<I>d</I>]oxazol-6(2<I>H</I>)-one moiety as their substituted heterocyclic residues, which is unprecedented in such types of meroterpenoids. Gauge-invariant atomic orbital NMR chemical shift calculations were employed to investigate stereochemical details with support of the application of advanced statistics such as CP3 and DP4. Compounds <B>2</B> and <B>8</B> and the mixture of <B>3</B> and <B>4</B> suppressed β-catenin response transcription (CRT) via degrading β-catenin and exhibited cytotoxic activity on colon cancer cells, implying that their anti-CRT potential is, at least in part, one of their underlying antineoplastic mechanisms.</P>

      • KCI등재

        Effect of SKL2001 on the neuronal survival mechanism in Parkinson’s disease

        Pyung jun Choi,Sangtaek Oh,Hyunjeong Liew,S. Oh,H. Liew 대한독성 유전단백체 학회 2017 Molecular & cellular toxicology Vol.13 No.2

        The Wnt/β-catenin pathway affects the differentiation of various cell types including mesenchymal stem cells. Previously, we evaluated SKL2001 as a novel agonist of the Wnt/β-catenin pathway. SKL2001 upregulated β-catenin-responsive transcription by increasing the intracellular β-catenin protein level and inhibiting the phosphorylation of β-catenin. Furthermore, SKL2001 disrupted Axin/β-catenin interaction and induced an increase in survivin, an inhibitor of apoptosis. We investigated the effect of SKL2001 on a Parkinson’s disease cell model consisting of SHSY5Y cells induced by 6-hydroxydopamine. Consequently, we discovered that SKL2001 is effective in promoting neuronal survival and functional recovery by activation of the Wnt/β-catenin signaling pathway

      • KCI등재후보

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