• Title/Summary/Keyword: B-cell depletion

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Development of Tumor Screening ELISA kit by Using Novel Tumor Antigen, CM1 (새로운 종양항원인 CM1을 이용한 종양 진단 ELISA kit의 개발)

  • Kang, Jae-Seung;Kim, Dae-Jin;Kim, Young-In;Chang, Ka-Young;Lee, Wang-Jae
    • IMMUNE NETWORK
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    • v.5 no.2
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    • pp.124-129
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    • 2005
  • Background: CM1 (centrocyte/-blast marker 1) is originally defined as a germinal center B cell marker. It is known that CM1 plays a critical role on B cell development in germinal center. In addition, we have found that CM1 is expressed on lymphoma cell lines, such as Raji, Ramos and IM-9. This means that CM1 might be served as a tumor marker as well. In the present study, we examined the expression of CM1 on the surface of the other tumors and the possibility of the development of tumor screening ELISA kit by using CM1. Methods: First, we have examined the expression of CM1 on stomach cancer and hepatoma, which are predominantly (discovered) occurred in Korean, by flow cytometry analysis. After purifying of CM1 antigen from Raji and Ramos, the optimal ELISA condition was determined. And then we compared the level of CM1 between normal individuals and cancer patients by ELISA. To decrease the non-specific binding of anti-CM1 mAb with serum components except CM1 and to enhance the diagnostic accuracy, albumin depletion spin column was used. Results: CM1 was highly expressed on stomach cancer and hepatoma cell lines. In addition, we have also confirmed the increased CM1 expression on cancer patients. The difference of CM1 expression between normal individuals and cancer patients were more clearly observed, after deletion of serum albumin by using albumin depletion spin column. Conclusion: Based on the results from this study, CM1 might be a useful molecule for the early diagnosis of cancer. In addition, further studies for the increase of ELISA sensitivity and appropriate albumin depletion methods should be needed.

Improvement and verification of the DeCART code for HTGR core physics analysis

  • Cho, Jin Young;Han, Tae Young;Park, Ho Jin;Hong, Ser Gi;Lee, Hyun Chul
    • Nuclear Engineering and Technology
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    • v.51 no.1
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    • pp.13-30
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    • 2019
  • This paper presents the recent improvements in the DeCART code for HTGR analysis. A new 190-group DeCART cross-section library based on ENDF/B-VII.0 was generated using the KAERI library processing system for HTGR. Two methods for the eigen-mode adjoint flux calculation were implemented. An azimuthal angle discretization method based on the Gaussian quadrature was implemented to reduce the error from the azimuthal angle discretization. A two-level parallelization using MPI and OpenMP was adopted for massive parallel computations. A quadratic depletion solver was implemented to reduce the error involved in the Gd depletion. A module to generate equivalent group constants was implemented for the nodal codes. The capabilities of the DeCART code were improved for geometry handling including an approximate treatment of a cylindrical outer boundary, an explicit border model, the R-G-B checker-board model, and a super-cell model for a hexagonal geometry. The newly improved and implemented functionalities were verified against various numerical benchmarks such as OECD/MHTGR-350 benchmark phase III problems, two-dimensional high temperature gas cooled reactor benchmark problems derived from the MHTGR-350 reference design, and numerical benchmark problems based on the compact nuclear power source experiment by comparing the DeCART solutions with the Monte-Carlo reference solutions obtained using the McCARD code.

Methyl Donor Status Influences DNMT Expression and Global DNA Methylation in Cervical Cancer Cells

  • Poomipark, Natwadee;Flatley, Janet E;Hill, Marilyn H;Mangnall, Barbara;Azar, Elnaz;Grabowski, Peter;Powers, Hilary J
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3213-3222
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    • 2016
  • Background: Methyl donor status influences DNA stability and DNA methylation although little is known about effects on DNA methyltransferases. The aim of this study was to determine whether methyl-donor status influences DNA methyltransferase (Dnmt) gene expression in cervical cancer cells, and if so, whether there are associated effects on global DNA methylation. Materials and Methods: The human cervical cancer cell line, C4-II, was grown in complete medium and medium depleted of folate (F-M+) and folate and methionine (F-M-). Growth rate, intracellular folate, intracellular methionine and homocysteine in the extracellular medium were measured to validate the cancer cell model of methyl donor depletion. Dnmt expression was measured by qRT-PCR using relative quantification and global DNA methylation was measured using a flow cytometric method. Results: Intracellular folate and methionine concentrations were significantly reduced after growth in depleted media. Growth rate was also reduced in response to methyl donor depletion. Extracellular homocysteine was raised compared with controls, indicating disturbance to the methyl cycle. Combined folate and methionine depletion led to a significant down-regulation of Dnmt3a and Dnmt3b; this was associated with an 18% reduction in global DNA methylation compared with controls. Effects of folate and methionine depletion on Dnmt3a and 3b expression were reversed by transferring depleted cells to complete medium. Conclusions: Methyl donor status can evidently influence expression of Dnmts in cervical cancer cells, which is associated with DNA global hypomethylation. Effects on Dnmt expression are reversible, suggesting reversible modulating effects of dietary methyl donor intake on gene expression, which may be relevant for cancer progression.

Numerical Study on Oxygen Depletion Characteristics of Porous Cathodes in Anode-Supported Solid Oxide Fuel Cells (음극지지 고체산화물 연료전지 다공성 양극에서의 산소고갈 특성에 관한 수치해석 연구)

  • Shin, Dongwoo;Nam, Jin Hyun;Kim, Charn-Jung
    • Transactions of the Korean Society of Mechanical Engineers B
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    • v.41 no.4
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    • pp.257-268
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    • 2017
  • This paper proposes an efficient two-dimensional simulation model for solid oxide fuel cells (SOFCs) based on the electrochemical effectiveness model. The effectiveness model is known to accurately predict the current generation performance of SOFC electrodes, by considering the complex reaction/transport processes that occur within thin active functional layers near the electrolyte. After validation tests, the two-dimensional simulation model was used to calculate the distribution of current density and oxygen concentration transverse to the flow channel in anode-supported SOFCs, with which the oxygen depletion characteristics were investigated in detail. In addition, simulations were also conducted to determine the minimum number of grids required in the transverse direction to efficiently obtain accurate results.

Targeted Immunotherapy for Autoimmune Disease

  • Seung Min Jung;Wan-Uk Kim
    • IMMUNE NETWORK
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    • v.22 no.1
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    • pp.9.1-9.23
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    • 2022
  • In the past few decades, biological drugs and small molecule inhibitors targeting inflammatory cytokines, immune cells, and intracellular kinases have become the standard-of-care to treat autoimmune diseases. Inhibition of TNF, IL-6, IL-17, and IL-23 has revolutionized the treatment of autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, and psoriasis. B cell depletion therapy using anti-CD20 mAbs has shown promising results in patients with neuroinflammatory diseases, and inhibition of B cell survival factors is approved for treatment of systemic lupus erythematosus. Targeting co-stimulatory molecules expressed on Ag-presenting cells and T cells is also expected to have therapeutic potential in autoimmune diseases by modulating T cell function. Recently, small molecule kinase inhibitors targeting the JAK family, which is responsible for signal transduction from multiple receptors, have garnered great interest in the field of autoimmune and hematologic diseases. However, there are still unmet medical needs in terms of therapeutic efficacy and safety profiles. Emerging therapies aim to induce immune tolerance without compromising immune function, using advanced molecular engineering techniques.

The Effect of Cortisol on Proliferative Properties of Flounder (Paralychthys Olivaceus) B Lymphocytes

  • Choi, Sang-Hoon;Oh, Chan-Ho
    • Animal cells and systems
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    • v.7 no.1
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    • pp.57-62
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    • 2003
  • Flounder B lymphocytes isolated from different tissues were studied in terms of cell proliferation, apoptosis and the effects of cortisol on these processes. B lymphocytes, isolated from the flounder head kidney and spleen, were characterized by higher proliferation and lower intracellular calcium ($Ca^2$) response to lgcrosslinking compared with peripheral blood B lymphocytes. Cortisol induced high levels of apoptosis (150% of control levels) in peripheral blood B lymphocytes, in combination with a stimulatory LPS signal. Head kidney and to a lesser extent spleen B lymphocytes, although less sensitive than their equivalent in peripheral blood, underwent cortisol-induced apoptosis irrespective of extra stimulation up to 142% of control levels. Also proliferation with and without LPS stimulation was suppressed by cortisol (compared to plasma values measured during stress conditions) that is effective in inducing a significant increase in apoptosis in all three populations of B-cells, suggesting that cortisol may be important for immunoregulation in both stressed and non-stressed conditions. This implies possible severe impact of stress on lymphocyte development and activity, Different sensitivity of B-cells to the corticosteroid, with respect to developmental stage and activity, may prevent excessive and long lasting depletion of B-lymphocytes.

Biological Activity of Tumor Necrosis Factor-α Secreted from Smooth Muscle Cell Overexpressing FADD (FADD 과발현 평활근세포에서 분비하는 Turner Necrosis Factor-α의 작용)

  • Kim, Sun-Mi;Lee, Kyeong-Ah;Kim, Koan-Hoi
    • Journal of Life Science
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    • v.17 no.1 s.81
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    • pp.45-50
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    • 2007
  • This study investigated biological activity of tumor necrosis factor $(TNF)-\alpha$ secreted from smooth muscle cell (SMC) destined for death by expressing Fas associated death domain containing protein (FADD) (FADD-SMC) when the cells are grown without tetracycline in culture medium. In the absence of tetracycline the FADD-SMC secreted approximately 1000 pg/ml $TNF-\alpha$, whereas hardly detectable amount of the cytokine existed in the presence of tetracycline. The culture medium collected from the FADD-SMC grown in the absence of tetracycline increased phosphorylated form of p38 MAPK and up-regulated nuclear factor kappa B (NF-kB). The medium collected without tetracycline also caused death of L929 cells. Depletion of $TNF-\alpha$ with the soluble TNF receptor (sTNFR) inhibited the phosphorylation of p38 MAPK, the up-regulation of NF-kB activity and the death activity of the medium collected from FADD-SMC in the absence of tetracycline. These results indicate that $TNF-\alpha$ secreted from SMC undergoing death is biologically active and can affect cellular function.

Hepatocyte protection and antioxidant effect of Citri Unshius Pericarpium against cadmium-induced oxidative stress (카드뮴으로 유발된 산화 스트레스에 대한 진피의 간세포 보호 및 항산화 효과)

  • Noh, Gyu Pyo;Byun, Sung Hui;Jung, Dae Hwa;Lee, Jong Rok;Park, Sook Jahr;Kim, Sang Chan
    • Herbal Formula Science
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    • v.28 no.4
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    • pp.327-337
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    • 2020
  • Objective : Citri Unshius Pericarpium is the dried peel of mature fruit of Citrus unshiu Markovich and has been used to treat indigestion, vomiting, and removal of phlegm. This study investigated the hepatoprotective and antioxidant effect of CEE (Ethanol extract of Citri Unshius Pericarpium) in cadmium (CdCl2)-treated HepG2 cells. Methods : Component analysis of Citri Unshius Pericarpium was analyzed by UPLC with C18 column. Cell viability was determined by MTT assay. The enzyme activity of superoxide dismutase (SOD) and the level of reactive oxygen species (ROS) and reduced glutathione (GSH) were analyzed using commercially available kits. Results : Cadmium caused severe HepG2 cell death. Cadmium also increased ROS production, consistent with depletion of GSH and inhibition of the SOD enzyme. However, CEE treatment reduced cell death and relieved oxidative stress caused by cadmium toxicity. CEE lowered ROS levels and improved depletion of GSH levels. CEE also enhanced the enzymatic activity of SOD. In component analysis, hesperidin was the most abundant of the five marker compounds (Narigenin, Narigin, Narirutin, Hesperidin and Hesperidin), which assumes that hesperidin partially contributed to the antioxidant activity of CEE. Conclusion : These results suggested that CEE could be a potential substance to solve heavy metal-related health problems. In particular, inhibition of oxidative stress by CEE can be a way to treat liver damage caused by cadmium.

Experimental Trichothecene (T-2) Toxicosis in Guinea pigs (기니픽그에서의 실험적 trichothecene (T-2) 독소중독증)

  • Kim, Jong-shu;Bak, Ung-bok
    • Korean Journal of Veterinary Research
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    • v.31 no.4
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    • pp.433-440
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    • 1991
  • Guinea pigs were administrated with T-2 toxin at a rate of 1 and 0.6mg/kg body weight per day for 21 days to study the immunological and pathological effects of T-2 toxin in guinea pigs. Blood was collected before T-2 treatment and on days 7, 14 and 21 of the trial for hematological and biological examinations and for the mitogen assay using lymphocytes. Myeloid: erythroid ratios were examined from the fernur bone marrow samples taken a day before T-2 toxin treatment began, on day 12 and at death. Guinea pigs received with 1mg/kg body weight of T-2 toxin daily showed leukopenic, lymphopenic and anemic signs on day 7 and 14. The mitogenic responses to the T-cell mitogen, Concanavalin A and B-cell mitogens, lipopolysaccharide were significantly depressed on day 7. Histologically, marked cellular damages including karyorrhexis and depletion of lymphocytes were observed in the actively dividing cells of the gastrointestinal tract, lymph node, spleen and bone marrow of guinea pigs.

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Exosomes from Murine-derived GL26 Cells Promote Glioblastoma Tumor Growth by Reducing Number and Function of CD8+T Cells

  • Liu, Zhi-Ming;Wang, Yu-Bin;Yuan, Xian-Hou
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.309-314
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    • 2013
  • Aim: Brain tumors almost universally have fatal outcomes; new therapeutics are desperately needed and will only come from improved understandins of glioma biology. Methods: Exosomes are endosomally derived 30~100 nm membranous vesicles released from many cell types. Examples from GL26 cells were here purified using density gradient ultracentrifugation and monitored for effects on GL26 tumor growth in C57BL/6j mice (H-2b). Lactate dehydrogenase release assays were used to detect the cytotoxic activity of CD8+T and NK cells. Percentages of immune cells producing intracellular cytokines were analyzed by FACS. Results: In this study, exosomes from murine-derived GL26 cells significantly promoted in vivo tumor growth in GL26-bearing B6 mice. Then we further analyzed the effects of the GL26 cells-derived exosomes on immune cells including CD8+T, CD4+T and NK cells. Inhibition of CD8+T cell cytotoxic activity was demonstrated by CD8+T cell depletion assays in vivo and LDH release assays in vitro. The treatment of mice with exosomes also led to a reduction in the percentages of CD8+T cells in splenocytes as determined by FACS analysis. Key features of CD8+T cell activity were inhibited, including release of IFN-gamma and granzyme B. There were no effects of exosomes on CD4+T cells and NK cells. Conclusion: Based on our data, for the first time we demonstrated that exosomes from murine derived GL26 cells promote the tumor growth by inhibition of CD8+T cells in vivo and thus may be a potential therapeutic target.