• Korean Journal of Clinical Laboratory Science
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• v.50 no.4
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• pp.462-469
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• 2018

HSP90 regulates various proteins involved in differentiation and cell survival. Levels of HSP90 tend to increase during development of squamous cell carcinoma in the head and neck including the mouth. Thus, many studies have been conducted to treat these cancers through suppression of HSP90. This study investigated the effect of two HSP90 inhibitors, geldanamycin and 17-AAG, on the proliferation, apoptosis, and invasion of human oral squamous cell carcinoma cells. Cell survival and cell cycle analyses, as well as western blot analysis, were performed with oral cancer cell lines, YD-10B and YD-38. After treatment with HSP90 inhibitors, cell proliferation was significantly inhibited. When YD-10B and YD-38 cells were treated with various concentrations of geldanamycin and 17-AAG (0, 0.1, 0.3, 1 and $10{\mu}M$) for 24 hr, the growth of YD-10B cells was markedly reduced compared to that of YD-38 cells. Thereafter, the cells were subjected to flow cytometry, which revealed G2 arrest. These results demonstrated that geldanamycin induced G2 arrest and inhibited cell proliferation through the $p-GSK-3{\beta}$ pathway in YD-10B and YD-38 cells, thus inhibiting cell survival. HSP90 inhibitors are therefore expected to have a therapeutic effect on various cancer cell lines.

• IMMUNE NETWORK
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• v.13 no.5
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• pp.205-212
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• 2013

Dectin-1, which specifically recognizes ${\beta}$-glucan of fungal cell walls, is a non-Toll-like receptor (TLR) pattern recognition receptor and a representative of C-type lectin receptors (CLRs). The importance of Dectin-1 in innate immune cells, such as dendritic cells and macrophages, has previously been well studied. However, the function of Dectin-1 in B cells is very poorly understood. To determine the role of Dectin-1 in B cell activation, we first investigated whether mouse B cells express Dectin-1 and then assessed the effect of Dectin-1 stimulation on B cell proliferation and antibody production. Mouse B cells express mRNAs encoding CLRs, including Dectin-1, and surface Dectin-1 was expressed in B cells of C57BL/6 rather than BALB/c strain. Dectin-1 agonists, heat-killed Candida albicans (HKCA) and heat-killed Saccharomyces cerevisiae (HKSC), alone induced B cell proliferation but not antibody production. Interestingly, HKSC, HKCA, and depleted zymosan (a selective Dectin-1 agonist) selectively enhanced LPS-driven IgG1 production. Taken together, these results suggest that, during fungal infection, ${\beta}$-glucan-stimulated Dectin-1 may cooperate with TLR4 to specifically enhance IgG1 production by mouse B cells.

• Journal of Microbiology and Biotechnology
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• v.28 no.10
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• pp.1760-1768
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• 2018

The type strain Bacillus subtilis subsp. subtilis KCTC $3135^T$ was deeply sequenced and annotated, replacing a previous draft genome in this study. The tar and tag genes were involved in synthesizing wall teichoic acids (WTAs), and these genes and their products were previously regarded as the distinguishing difference between B. s. subtilis and B. s. spizizenii. However, a comparative genomic analysis of B. subtilis spp. revealed that both B. s. subtilis and B. s. spizizenii had various types of cell walls. These tar and tag operons were mutually exclusive and the tar genes from B. s. spizizenii were very similar to the genes from non-Bacillus bacteria, unlike the tag genes from B. s. subtilis. The results and previous studies suggest that the tar genes and the tag genes are not inherited after subspecies speciation. The phylogenetic tree based on whole genome sequences showed that each subspecies clearly formed a monophyletic group, while the tree based on tar genes showed that monophyletic groups were formed according to the cell wall type rather than the subspecies. These findings indicate that the tar genes and the presence of ribitol as a cell-wall constituent were not the distinguishing difference between the subspecies of B. subtilis and that the description of subspecies B. s. spizizenii should be updated.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1299-1308
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• 2016

Our previous studies clearly demonstrated that a combination of WP 631 and Epo B has higher activity against ovarian cancer cells than either of these compounds used separately. In order to fully understand the exact mechanism of action in combination, we assessed effects on the cell cycle of SKOV-3 cells. We evaluated three control points essential for WP 631 and Epo B action to determine which cell cycle-regulating proteins (CDK1/cyclin B complex, EpCAM or HMGB1) mediate activity. The effects of the drug on the cell cycle were measured based on the nuclear DNA content using flow cytometry. Expression of cell cycle-regulating genes was analyzed using real-time PCR. It was discovered that WP 631, at the tested concentration, did not affect the SKOV-3 cell cycle. Epo B caused significant G2/M arrest, whereas the drug combination induced stronger apoptosis and lower mitotic arrest than Epo B alone. This is very important information from the point of view of the fight against cancer, as, while mitotic arrest in Epo B-treated cells could be overcame after DNA damage repair, apoptosis which occurs after mitotic slippage in combination-treated cells is irreversible. It clearly explains the higher activity of the drug combination in comparison to Epo B alone. Epo B acts via the CDK1/cyclin B complex and has the ability to inhibit CDK1, which may be a promising strategy for ovarian cancer treatment in the future. The drug combination diminishes EpCAM and HMGB1 expression to a greater degree than either WP 631 and Epo B alone. Owing to the fact that the high expression of these two proteins is a poor prognostic factor for ovarian cancer, a decrease in their expression, observed in our studies, may result in improved efficacy of cancer therapy. The presented findings show that the combination of WP 631 and Epo B is a better therapeutic option than either of these drugs alone.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.28 no.1
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• pp.114-122
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• 1995

Defining the mechanisms of B cell diversification which establish the immune repertoire is fundamental to understand how the immune response is regulated. In this report, B cell differentiation and diversification focused on the regulation of immunoglobulin $V_H$ gene expression during ontogeny were analyzed by in situ hybridization technique. Fetal liver B cells in .different gestational days from 16d to 20d showed the predominant expression of $V_H7183$ and $V_HQ52$ without transition of repertoire during the observed gestation days. The two subsets of fetal liver B cells separated according to different differentiation stages based on the presence of tell surface immunoglobulin also did not indicate apparent difference in expressed $V_H$ gene family profiles. B cells in fetal spleen as an another hematopoietic lymphoid tissue in fetus also expressed similar $V_H$ gene repertoire to that in fetal liver B cells. This distinct pattern of $V_H$ gene expression in fetal B cells from that of adult B cells were not changed even after four weeks contact with adult bone marrow microenvironment supplied by the established adult bone marrow stromal cell layers. Thus, the restricted $V_H$ gene repertoire of B cells in fetus which is distinct from that in adult appears to be associated more with the genetic potential of fetal B cell progenitors and less with environmental influences or differentiation stages or compartmentalization.

• BMB Reports
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• v.43 no.12
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• pp.807-812
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• 2010

$NF{\kappa}B$ and ZAS3 are transcription factors that control important cellular processes including immunity, cell survival and apoptosis. Although both proteins bind the ${\kappa}B$-motif, they produce opposite physiological consequences; $NF{\kappa}B$ activates transcription, promotes cell growth and is often found to be constitutively expressed in cancer cells, while ZAS3 generally represses transcription, inhibits cell proliferation and is downregulated in some cancers. Here, we show that ZAS3 inhibits $NF{\kappa}B$-dependent transcription by competing with $NF{\kappa}B$ for the ${\kappa}B$-motif. Transient transfection studies show that N-terminal 645 amino acids is sufficient to repress transcription activated by $NF{\kappa}B$, and that the identical region also possesses intrinsic repression activity to inhibit basal transcription from a promoter. Finally, in vitro DNA-protein interaction analysis shows that ZAS3 is able to displace $NF{\kappa}B$ by competing with $NF{\kappa}B$ for the ${\kappa}B$-motif. It is conceivable that ZAS3 has therapeutic potential for controlling aberrant activation of $NF{\kappa}B$ in various diseases.

• BMB Reports
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• v.51 no.11
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• pp.602-607
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• 2018

Aberrant expression of microRNAs (miRNAs) plays important roles in carcinogenesis and tumor progression. However, the expression and biological role of miR-301b in triple-negative breast cancer (TNBC) remains unclear. Here we aimed to evaluate the roles and mechanisms of miR-301b in TNBC cells. miR-301b expression was assessed in TNBC specimens and cell lines by quantitative Real-Time PCR (qRT-PCR). TNBC cells were transfected with miR-301b mimics, inhibitors or Cylindromatosis (CYLD) small interfering RNA (siRNA) using Lipofectamine 2000. The functional roles of miR-301b were determined by cell proliferation, colony formation, and apoptosis assays. Western blots and qRT-PCR were used to measure the expression of mRNAs and proteins in the cells. We found that miR-301b was upregulated in TNBC specimens and cell lines. Overexpression of miR-301b promoted cell proliferation in TNBC cells, while inhibited the apoptosis induced by 5-FU. CYLD was downregulated by miR-301b at both mRNA and protein levels in TNBC cells. Dual-luciferase report assay confirmed that miR-301b downregulated CYLD by direct interaction with the 3'-untranslated region(3'-UTR) of CYLD mRNA. $NF-{\kappa}B$ activation was mechanistically associated with miR-301b-mediated downregulation of CYLD. However, inhibition of miR-301b reversed all the effects of miR-301b. In conclusion, miR-301b plays an oncogenic role in TNBC possibly by downregulating CYLD and subsequently activating $NF-{\kappa}B$ p65, and this may provide a novel therapeutic approach for TNBC.

• Korean Journal of Radiology
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• v.24 no.4
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• pp.362-370
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• 2023

Objective: To report the clinical and radiological characteristics of patients with underlying B-cell lymphoma and coronavirus disease 2019 (COVID-19) showing migratory airspace opacities on serial chest computed tomography (CT) with persistent COVID-19 symptoms. Materials and Methods: From January 2020 to June 2022, of the 56 patients with underlying hematologic malignancy who had undergone chest CT more than once at our hospital after acquiring COVID-19, seven adult patients (5 female; age range, 37-71 years; median age, 45 years) who showed migratory airspace opacities on chest CT were selected for the analysis of clinical and CT features. Results: All patients had been diagnosed with B-cell lymphoma (three diffuse large B-cell lymphoma and four follicular lymphoma) and had received B-cell depleting chemotherapy, including rituximab, within three months prior to COVID-19 diagnosis. The patients underwent a median of 3 CT scans during the follow-up period (median 124 days). All patients showed multifocal patchy peripheral ground glass opacities (GGOs) with basal predominance in the baseline CTs. In all patients, follow-up CTs demonstrated clearing of previous airspace opacities with the development of new peripheral and peribronchial GGO and consolidation in different locations. Throughout the follow-up period, all patients demonstrated prolonged COVID-19 symptoms accompanied by positive polymerase chain reaction results from nasopharyngeal swabs, with cycle threshold values of less than 25. Conclusion: COVID-19 patients with B-cell lymphoma who had received B-cell depleting therapy and are experiencing prolonged SARS-CoV-2 infection and persistent symptoms may demonstrate migratory airspace opacities on serial CT, which could be interpreted as ongoing COVID-19 pneumonia.

• The Korean Journal of Zoology
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• v.33 no.4
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• pp.446-453
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• 1990

In order to investigate the retinoic acid indticed-differentiation of F9 teratocarcinoma stem cell, we have analyzed the change of cell morphology and laminin expression after exposure to retinoic add and cyclic AMP. It is shown that undifferentiated F9 stem cells grow as closely packed colonies, and it is difficult to distinguish cell-cell boundaries. After retinoic add and dibutyryl cyclic AMP treatment, F9 cells assume a flat morphology characterized by perinuclear granules and arrest growth. According to Northern blot analysis, laminin expression was increased markedly after retinoic acid treatment. Laminin Bi gene expression was increased at least 30-fold and laminin B2 gene expression was increased approximately 20-fold during differentiation process. Employing immunofluoresence analysis, it was proved that the synthesis of laminin protein was low level in F9 stem cell whereas it became high level in retinoic acid treated F9 cell and the laminin protein was largely accumulated in the cell surface. Our results suggest that induction of laminin Bi and B2 genes m F9 cells is retinoic acid-mediated control, and morphological change and differentiation of F9 cells might be associated with laminin gene expression.

• Journal of Korean Neurosurgical Society
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• v.29 no.12
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• pp.1628-1633
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• 2000

Objective : The incidence of primary CNS lymphoma(PCNSL) has been increasing recently. The purpose of this study is to establish of prognostic factors and treatment options for PCNSL. Methods : Thirty-one PCNSL patients were treated in our institute between 1985 and 1997. All patients were histologically confirmed via stereotactic biopsy or open biopsy. The authors retrospectively analyzed clinical characteristics of PCNSL and prognostic factors, including histological cell types, immunohistological cell types and treatment options of PCNSL. Our data were statistically analyzed using Kaplan Meier survival curve and multivariated ANOVA test. Results : The clinical and radiological characteristics of PCNSL were resembled to those of other reports. The most common histological subtype was diffuse large cell type(55.5%). In immunohistolgical study, the incidence of T-cell lymphoma(35.7%) was very higher than that of others. The radiotherapy could prolonged patients' survival(p=0.021). One-year and 3-year survival rate of PCNSL were 66.9% and 45.9%, respectively. One-year survival rate of B cell and T cell lymphoma were 72.7% and 50.0%, respectively. The patients with B-cell lymphoma showed better prognosis than patients with T-cell lymphoma(p=0.049). Conclusion : On the basis of our data, active radiotherapy could prolong patients' survival. the T-cell lymphoma revealed higher incidence than those of other reports and had poor prognosis than that of B cell lymphoma.