Immunity to melanoma mediated by 4‐1BB is associated with enhanced activity of tumour‐infiltrating lymphocytes

Ju, Seong‐,A,Lee, Sang‐,Chul,Kwon, Tae‐,Hyoung,Heo, Sook‐,Kyoung,Park, Sang‐,Min,Paek, Ha‐,Na,Suh, Jae‐,Hee,Cho, Hong Rae,Kwon, Byungsuk,Kwon, Byoung S,Kim, B Nature Publishing Group 2005 Immunology and Cell Biology Vol.83 No.4

<P>4‐1BB costimulates T cells to carry out effector functions such as eradication of established tumours. 4‐1BB (CD137) is a member of the TNF receptor family, and its triggering by either 4‐1BB ligand or antibody ligation induces T‐cell activation and growth. We analysed tumour‐infiltrating lymphocytes (TIL) in the experimental B16F10 melanoma model to determine the mechanisms involved in 4‐1BB‐mediated tumour suppression. 4‐1BB<SUP>+/+</SUP> mice survived longer than 4‐1BB<SUP>–/–</SUP> mice, and survival was further prolonged by triggering 4‐1BB with an agonistic mAb. The number of metastatic B16F10 colonies in the lung was much greater in 4‐1BB<SUP>–/–</SUP> mice than in their 4‐1BB<SUP>+/+</SUP> littermates. Administration of agonistic anti‐4‐1BB mAb increased the number of TIL in the tumour masses in the lungs of 4‐1BB<SUP>+/+</SUP> mice. The numbers of CD4<SUP>+</SUP> T, CD8<SUP>+</SUP> T and CD11b<SUP>+</SUP> TIL increased in these mice. Anti‐4‐1BB mAb induced not only CD8<SUP>+</SUP> 4‐1BB<SUP>+</SUP> T cells but also a CD8<SUP>+</SUP> IFN‐γ<SUP>+</SUP> T‐cell population. B16F10 cells from the lungs of anti‐4‐1BB‐treated mice showed enhanced expression of MHC class Ι and II antigens compared with the same cells from control IgG‐treated mice. Thus, the increase in number of CD8<SUP>+</SUP> T cells and enhanced MHC Ι and II expression in B16F10 cells that result from augmented IFN‐γ production in response to anti‐4‐1BB mAb may lead to suppression of tumour growth and metastasis.</P>

난소과자극 증후군 1예

이병석,박기현,박찬규,허갑범,이현철,임승길,조용욱,김유곤 대한내분비학회 1988 Endocrinology and metabolism Vol.3 No.2

Ovarian hyperstimulation syndrome (OHS) is a rare complication in the use of human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG) for ovulation induction. The pathophysiology is unclear and treatments are mainly conservative. We presented a case of ovulation induction with HMG and HCG in secondary amenorrhea due to hypogonadotropic hypogonadism after brain surgery for craniopharyngeoma with abscess formation. A brief review on the literatures was made in comment.

선택적 남성 호르몬 분비 부신피질 종양 1예

김동수,박정수,이상주,이병석,박기현,박찬규,허갑범,이현철,이관우,김미림,이명래 대한내분비학회 1989 Endocrinology and metabolism Vol.4 No.2

Hepatitis C Virus Nonstructural 4B Protein Modulates Sterol Regulatory Element-binding Protein Signaling via the AKT Pathway

Park, Chul-Yong,Jun, Hyun-Jeong,Wakita, Takaji,Cheong, Jae Hun,Hwang, Soon B. American Society for Biochemistry and Molecular Bi 2009 The Journal of biological chemistry Vol.284 No.14

<P>Hepatitis C virus (HCV) infection is often associated with hepatic steatosis and yet the molecular mechanisms of HCV-associated steatosis are poorly understood. Because sterol regulatory element-binding proteins (SREBPs) are the major transcriptional factors in lipogenic gene expression including fatty acid synthase (FAS), we examined the effects of HCV nonstructural proteins on the signaling pathways of SREBP. In this study, we demonstrated that HCV nonstructural 4B (NS4B) protein increased the transcriptional activities of SREBPs. We also showed that HCV NS4B enhanced the protein expression levels of SREBPs and FAS. This was further confirmed in the context of viral RNA replication and HCV infection. The up-regulation of both SREBP and FAS by NS4B protein required phosphatidylinositol 3-kinase activity. We also demonstrated that NS4B protein induced a lipid accumulation in hepatoma cells. In addition, NS4B protein synergistically elevated the transcriptional activity of HCV core-mediated SREBP-1. These results strongly suggest that NS4B may play an important role in HCV-associated liver pathogenesis by modulating the SREBP signaling pathway.</P>

Nitrogen doped BiFeO₃ with enhanced magnetic properties and photo-Fenton catalytic activity for degradation of bisphenol A under visible light

Jia, Yuefa,Wu, Changjin,Kim, Deok-Hyeon,Lee, B.W.,Rhee, S.J.,Park, Yun Chang,Kim, Chul Sung,Wang, Q.J.,Liu, Chunli Elsevier 2018 CHEMICAL ENGINEERING JOURNAL -LAUSANNE- Vol.337 No.-

<P><B>Abstract</B></P> <P>In the present work, N doped BiFeO<SUB>3</SUB> (N-BFO) nanoparticles have been synthesized via a sol-gel rapid calcination technique using melamine (C<SUB>3</SUB>H<SUB>6</SUB>N<SUB>6</SUB>) as the N precursor. It is found that N-doping could effectively narrow the band gap of BFO, which obviously enhanced the visible light adsorption capability. Meanwhile, N-doping could lead to significant increase in the magnetization of BFO. Particularly, the saturation magnetization (<I>M<SUB>s</SUB> </I>) was increased up to 0.35 emu/g (as compared to that of pure BFO: 0.07 emu/g) when 12.5 mmol N doping precursor was used (12.5N-BFO). The catalytic performance of N-BFO nanoparticles was evaluated through the degradation of bisphenol A (BPA) under visible light irradiation. 12.5N-BFO was found to be an efficient catalyst of BPA, and the addition of H<SUB>2</SUB>O<SUB>2</SUB> (10 mmol/L) or H<SUB>2</SUB>O<SUB>2</SUB> (10 mmol/L)/<SMALL>L</SMALL>-cysteine (0.25 mmol/L) can further enhance the degradation efficiency up to 60% and 94% within 120 min, respectively. The 12.5N-BFO nanoparticles were very stable during photocatalytic processes and their photo-Fenton catalytic activity can be retained even after three recycling processes.</P> <P><B>Highlights</B></P> <P> <UL> <LI> N doped BiFeO<SUB>3</SUB> have been synthesized using melamine as the N precursor. </LI> <LI> The band gap and saturation magnetization of N doped BiFeO<SUB>3</SUB> is tunable. </LI> <LI> N doped BiFeO<SUB>3</SUB>/H<SUB>2</SUB>O<SUB>2</SUB> shows enhanced efficient degradation of bisphenol A. </LI> <LI> Addition of <SMALL>L</SMALL>-cysteine can further enhanced photodegradation performance. </LI> <LI> A mechanism of bisphenol A degradation was proposed. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Hepatitis delta virus large antigen sensitizes to TNF-α-induced NF-κB signaling

Park, Chul-Yong,Oh, Sang-Heun,Kang, Sang Min,Lim, Yun-Sook,Hwang, Soon B. Springer-Verlag 2009 Molecules and cells Vol.28 No.1

<P>Hepatitis delta virus (HDV) infection causes fulminant hepatitis and liver cirrhosis. To elucidate the molecular mechanism of HDV pathogenesis, we examined the effects of HDV viral proteins, the small hepatitis delta antigen (SHDAg) and the large hepatitis delta antigen (LHDAg), on NF-kappaB signaling pathway. In this study, we demonstrated that TNF-alpha-induced NF-kappaB transcriptional activation was increased by LHDAg but not by SHDAg in both HEK293 and Huh7 cells. Furthermore, LHDAg promoted TRAF2-induced NF-kappaB activation. Using coimmunoprecipitation assays, we demonstrated that both SHDAg and LHDAg interacted with TRAF2 protein. We showed that isoprenylation of LHDAg was not required for the increase of NF-kappaB activity. We further showed that only LHDAg but not SHDAg increased the TNF-alpha-mediated nuclear translocation of p65. This was accomplished by activation of IkappaBalpha degradation by LHDAg. Finally, we demonstrated that LHDAg augmented the COX-2 expression level in Huh7 cells. These data suggest that LHDAg modulates NF-kappaB signaling pathway and may contribute to HDV pathogenesis.</P>

WIG1 is crucial for AGO2-mediated <i>ACOT7</i> mRNA silencing via miRNA-dependent and -independent mechanisms

Lee, Hyung Chul,Jung, Seung Hee,Hwang, Hyun Jung,Kang, Donghee,De, Supriyo,Dudekula, Dawood B.,Martindale, Jennifer L.,Park, Byungkyu,Park, Seung Kuk,Lee, Eun Kyung,Lee, Jeong-Hwa,Jeong, Sunjoo,Han, K Oxford University Press 2017 Nucleic acids research Vol.45 No.11

<P><B>Abstract</B></P><P>RNA-binding proteins (RBPs) are involved in mRNA splicing, maturation, transport, translation, storage and turnover. Here, we identified <I>ACOT7</I> mRNA as a novel target of human WIG1. <I>ACOT7</I> mRNA decay was triggered by the microRNA miR-9 in a WIG1-dependent manner via classic recruitment of Argonaute 2 (AGO2). Interestingly, AGO2 was also recruited to <I>ACOT7</I> mRNA in a WIG1-dependent manner in the absence of miR-9, which indicates an alternative model whereby WIG1 controls AGO2-mediated gene silencing. The WIG1–AGO2 complex attenuated translation initiation via an interaction with translation initiation factor 5B (eIF5B). These results were confirmed using a WIG1 tethering system based on the MS2 bacteriophage coat protein and a reporter construct containing an MS2-binding site, and by immunoprecipitation of WIG1 and detection of WIG1-associated proteins using liquid chromatography-tandem mass spectrometry. We also identified WIG1-binding motifs using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation analyses. Altogether, our data indicate that WIG1 governs the miRNA-dependent and the miRNA-independent recruitment of AGO2 to lower the stability of and suppress the translation of <I>ACOT7</I> mRNA.</P>

Interleukin‐32 enhances cytotoxic effect of natural killer cells to cancer cells via activation of death receptor 3

Park, Mi H.,Song, Min J.,Cho, Min‐,Chul,Moon, Dong C.,Yoon, Do Y.,Han, Sang B.,Hong, Jin T. Blackwell Publishing Ltd 2012 Immunology Vol.135 No.1

<P><B>Summary</B></P><P>Studies have demonstrated that the anti‐tumour effect of natural killer (NK) cells is successful for patients with several cancers. Although interleukin‐32 (IL‐32) is endogenously expressed in NK cells, cytolytic function of NK cells against cancer cells has not been fully demonstrated. In the present study, we found that the growth of cancer cells was suppressed when colon cancer cells or prostate cancer cells were co‐cultured with NK‐92 cells, an NK cell line. We also found that the expression of tumour necrosis factor receptor 2 and death receptor 3 (DR3) was increased in PC3 cells, and the expression of FAS and DR3 was increased in SW620 cells by co‐culture with NK‐92 cells. However, cancer cell growth inhibition and IL‐32 expression were abolished when cancer cells were co‐cultured with NK cells transfected with small interfering (si) RNA of IL‐32. DR3 expression was also diminished by co‐culture with IL‐32‐specific siRNA‐transfected NK‐92 cells. Expression of APO3L, a ligand of DR3, was elevated in NK cells that were co‐cultured with cancer cells. It was also found that expression of apoptosis‐related proteins such as cleaved caspase‐3 and bax was increased in cancer cells co‐cultured with NK‐92 cells, but their expression was abolished by co‐culture with IL‐32 siRNA‐transfected NK‐92 cells. Moreover, knockdown of DR3 in co‐culture of NK‐92 cells with cancer cells by siRNA or antibodies of DR3 and APO3L reversed the growth inhibitory effect of NK‐92 cells. In conclusion, our study showed that IL‐32 enhanced the cytotoxic effect of NK‐92 cells on the cancer cells through activation of DR3 and caspase‐3.</P>

Hepatitis Delta Virus Large Antigen Sensitizes to TNF-α-Induced NF-κB Signaling

Chul-Yong Park,Sang-Heun Oh,Sang Min Kang,Yun-Sook Lim,Soon B. Hwang 한국분자세포생물학회 2009 Molecules and cells Vol.28 No.1

Hepatitis delta virus (HDV) infection causes fulminant hepatitis and liver cirrhosis. To elucidate the molecular mechanism of HDV pathogenesis, we examined the effects of HDV viral proteins, the small hepatitis delta antigen (SHDAg) and the large hepatitis delta antigen (LHDAg), on NF-κB signaling pathway. In this study, we demonstrated that TNF-α-induced NF-κB transcriptional activation was increased by LHDAg but not by SHDAg in both HEK293 and Huh7 cells. Furthermore, LHDAg promoted TRAF2-induced NF-κB activation. Using coimmunoprecipitation assays, we demonstrated that both SHDAg and LHDAg interacted with TRAF2 protein. We showed that isoprenylation of LHDAg was not required for the increase of NF-κB activity. We further showed that only LHDAg but not SHDAg increased the TNF-α-mediated nuclear translocation of p65. This was accomplished by activation of IκBα degradation by LHDAg. Finally, we demonstrated that LHDAg augmented the COX-2 expression level in Huh7 cells. These data suggest that LHDAg modulates NF-κB signaling pathway and may contribute to HDV pathogenesis.

Computer-Assisted Image Processing Techniques for Quantitative Analysis of Cell Migrations on Collagen-Coated Glass

Park, B.J.,Kim, Seok Cheol,Lee, D.H.,Son, Hyun Joo,Nam, K.C.,Takatori, K.,Aihara, M.,Park, Jong Chul Trans Tech Publications, Ltd. 2005 Key Engineering Materials Vol.288 No.-

<P>In this study, a computer-assisted cell tracking system including an automatic image processing program for rapid and precise analysis of cell migration in various conditions was self-designed and L-929 cell migration on the glass coated with type I collagen was examined using this cell tracking system. Furthermore, computer-based image processing software, with the capture program to choose the capture interval and period, and analysis techniques were developed for quantitative analysis of the cell migration on extracellular matrices. The results showed that the migration speed of L-929 cells on the collagen-coated glass was significantly (p < 0.05) increased compared to the non-coated control. On the morphological observations, it was showed that the cells on the collagen-coated glass looked much healthier than those on the control. These results suggested that this cell tracking system would provide tools for the analysis of cell migration in various in vitro conditions and might be effective enough to evaluate various biological events including embryonic development as well as physiological and pathological tissue reorganization.</P>