• Journal of Breast Disease
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• v.6 no.2
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• pp.52-59
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• 2018

Purpose: This study aimed to determine whether clinicopathological factors are potentially associated with successful breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NAC) and develop a nomogram for predicting successful BCS candidates, focusing on those who are diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative tumors during the pre-NAC period. Methods: The training cohort included 239 patients with an HR-positive, HER2-negative tumor (${\geq}3cm$), and all of these patients had received NAC. Patients were excluded if they met any of the following criteria: diffuse, suspicious, malignant microcalcification (extent >4 cm); multicentric or multifocal breast cancer; inflammatory breast cancer; distant metastases at the time of diagnosis; excisional biopsy prior to NAC; and bilateral breast cancer. Multivariate logistic regression analysis was conducted to evaluate the possible predictors of BCS eligibility after NAC, and the regression model was used to develop the predicting nomogram. This nomogram was built using the training cohort (n=239) and was later validated with an independent validation cohort (n=123). Results: Small tumor size (p<0.001) at initial diagnosis, long distance from the nipple (p=0.002), high body mass index (p=0.001), and weak positivity for progesterone receptor (p=0.037) were found to be four independent predictors of an increased probability of BCS after NAC; further, these variables were used as covariates in developing the nomogram. For the training and validation cohorts, the areas under the receiver operating characteristic curve were 0.833 and 0.786, respectively; these values demonstrate the potential predictive power of this nomogram. Conclusion: This study established a new nomogram to predict successful BCS in patients with HR-positive, HER2-negative breast cancer. Given that chemotherapy is an option with unreliable outcomes for this subtype, this nomogram may be used to select patients for NAC followed by successful BCS.

• Journal of Periodontal and Implant Science
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• v.35 no.2
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• pp.427-436
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• 2005

Objective: MMP-8 is a neutrophil enzyme and its level increases in some inflammatory diseases, including periodontal disease. We knew that the lipopolysaccharide of E.coli(E-LPS) induced MMP-8 release from human neutrophils. E-LPS is known to induce the production and release of inflammatory cytokines through CD14, Toll-like receptor(TLR). In the present study, we investigated whether MMP-8 release by E-LPS is induced via CD14-TLR pathway and the cellular mechanism of MMP-8 release in human neutrophils. Material and methods: Human neutrophils were isolated from the peripheral blood of healthy donors and pre-incubated in medium containing antibodies against CD14, anti-TLR2 and anti-TLR4 or several inhibitors of microtubules and microfilaments and then incubated with E-LPS. The cells were treated TPCK and E-LPS simultaneously. The MMP-8amount in the culture medium was determined using ELISA. Results: E-LPS increased MMP-8release from neutrophils and its induction was inhibited by anti-CD14 and anti-TLR4 but not by anti-TLR2 antibodies. The inhibitors of microtubule and microfilament polymerization significantly decreased E-LPS-induced MMP-8release. TPCK inhibited E-LPS-induced MMP-8 release. Conclusion: These results suggest that MMP-8 release is induced by E-LPS via the CD14-TLR4 signal pathway in human neutrophils and may be depedent on microtubule and microfilament systems and $NF-{\kappa}B$ pathway.

• Journal of Ginseng Research
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• v.22 no.1
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• pp.22-31
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• 1998

Antiulcer effects of ginseng saponin, acidic polysaccharide and methanol extract of Panax ginseng in the patients and experimental animals were reported. Postulated action mechanisms of ginseng were histamine-Ht receptor blocking and increasing gastric blood flow In the present study, the effect of ginsenosides, the biologically active glycosides of ginseng, on gastric acid secretion was examined using gastric cells isolated from human and rabbit gastric mucosa. Ginseng saponin, ginsenoside $Rb_1$, $Rb_2$, $Rg_1$ and $Rh_2$ were tested in unstimulated as well as stimulated gastric cells. Histamine ($10^4$M) and 3-isobutyl-1-methylxanthine ($10^4$M) were used as secretagogues. To investigate the mechanism of ginsenosides on acid secretion, the levels of cAMP and cGMP were monitored in gastric cells. As a result, high concerltration(1mg/ml) of ginseng saponin showed 73-75% of stimulated acid secretion in control gastric cells. However, ginseng saponin had no effect on unstimulated acid secretion and the levels of cGMP and cAMP in gastric cells. Ginsenoside $Rb_1$, $Rb_2$ and $Rh_2$ significantly inhibited stimulated acid secretion. Gastric cGMP levels were increased by all ginsenosides tested while cAMP levels were increased by all ginsenosides in unstimulated state of gastric cells, but increased by ginsenosides ginsenoside $Rg_1$ and $Rh_2$in stimulated state of gastric cells. The results suggest that inhibition of ginseng saponin on gastric acid secretion represents a complex effect of individual ginsenosides, which produce a range of effect on acid secretion. The inhibition site of ginseng saponin on stimulated acid secretion is postulated as post cAMP levels in acid secretary pathway such as protein phosphorylation or proton pump. Nitric oxide may not be involved in the inhibitory effect of ginseng saponin on stimulated acid secretion.

• Journal of Microbiology and Biotechnology
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• v.19 no.2
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• pp.208-214
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• 2009

Steroid hormones have long been known to have a profound influence on the immune system. Although the functions of the nuclear receptors in the development of T cells are fairly well studied, the differential expression of these receptors in T helper cells is poorly understood. Here, we investigated the differential expression of nuclear receptors and coregulators in Th1 and Th2 cells by genome-wide micro array analysis. The result showed that several nuclear receptors and coregulators are differentially expressed in these cells. The result was confirmed by RT-PCR. The result showed that $RXR{\alpha}$ is highly expressed in Th2 cells. Overexpression of $RXR{\alpha}$ in a Jurkat human T cell line induced IL4 but not IFN-${\gamma}$ gene expression, suggesting that $RXR{\alpha}$ plays a selective role in Th1 and Th2 differentiation. In summary, these results suggest that Th1/Th2 differentiation is influenced by differential regulation of nuclear receptors and coregulators.

• Journal of Life Science
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• v.19 no.3
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• pp.299-304
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• 2009

Interleukin 27 (IL-27) was discovered as a heterodimeric cytokine of the IL-12 family, and is composed of two subunits - Epstein-Barr virus induced gene 3 (EBI3) and p28. It acts as a versatile cytokine in the early regulation of Th1 initiation and in the negative regulation of the Th2 factor GATA binding protein 3 (GATA-3). This cytokine is mediated by the IL-27 receptor (WSX-1), which is highly expressed on $CD4^+$ T lymphocytes and NK cells. We previously identified four polymorphisms in the human IL-27p28 gene and suggested that the polymorphism of IL-27p28 is associated with susceptibility to asthma. To determine whether these IL-27p28 SNPs are associated with susceptibility to allergic rhinitis, the genotype and allele frequencies of IL-27p28 SNPs were analyzed between allergic rhinitis patients and healthy controls. Although the genotype and allele frequencies of IL-27p28 SNPs in allergic rhinitis patients were not significantly different from those of the control group, there was a suggestive difference (P=0.037) between these groups in total serum IgE levels in the g.2905T>G SNP of the IL-27p28 gene. Our result implies that the g.2905T>G SNP of the IL-27p28 gene might have an affect on IgE production in allergic rhinitis patients.

• BMB Reports
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• v.56 no.6
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• pp.359-364
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• 2023

KAI1/CD82, a membrane tetraspanin protein, can prevent various cancers and retinal disorders through its anti-angiogenic and anti-metastatic capacity. However, little is known about its anti-inflammatory effect and molecular mechanism. Therefore, the present study aimed to inLPSvestigate effect of a recombinant protein of the large extracellular domain of human KAI1 (Gly 111-Leu 228, rhKAI1) on lipopolysaccharides (LPS)-stimulated RAW264.7 macrophage-like cells and mouse bone marrow-derived macrophages (BMDM) and to identify its underlying mechanism. Our data showed that rhKAI1 suppressed expression levels of classically macrophages (M1) phenotype-related surface markers F4/80+CD86+ in LPS-stimulated BMDM and RAW264.7 cells. In addition, LPS markedly increased mRNA expression and release levels of pro-inflammatory cytokines and mediators such as interleukin (IL)-1β, IL-6, tumor necrosis factor-α, cyclooxygenase-2, nitric oxide and prostaglandin E2, whereas these increases were substantially down-regulated by rhKAI1. Furthermore, LPS strongly increased expression of NF-κB p65 in the nuclei and phosphorylation of ERK, JNK, and p38 MAPK. However, nuclear translocation of NF-κB p65 and phosphorylation of JNK were greatly reversed in the presence of rhKAI1. Especially, rhKAI1 markedly suppressed expression of toll-like receptor (TLR4) and prevented binding of LPS with TLR4 through molecular docking predict analysis. Importantly, Glu 214 of rhKAI1 residue strongly interacted with Lys 360 of TLR4 residue, with a binding distance of 2.9 Å. Taken together, these findings suggest that rhKAI1 has an anti-inflammatory effect on LPS-polarized macrophages by interacting with TLR4 and down-regulating the JNK/NF-κB signaling pathway.

• Animal cells and systems
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• v.1 no.4
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• pp.657-663
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• 1997

The CD4 and CDS coreceptors, in conjunction with the T cell receptor (TCR) , make important contributions to the differentiation of thymocytes. They have been shown to be involved in the clonal deletion and positive selection processes during T cell development in thymus. To further analyze the role of CD4 and CDS proteins during T cell differentiation, we have generated transgenic mice constitutively expressing high levels of a native CD4 and a CD4{CDSa hybrid protein. The hybrid protein is composed of CD4 extracellular domain linked to the CD8a transmembrane region and cytoplasmic tail. The transgenes were driven by human beta-actin promoter, and therefore, they were expressed in all tissues examined including thymus, spleen, and lymph nodes. The resulting CD4 and CD4{CD8${\alpha}$transgenic mice were found to express the CD4 and CD4{CD8${\alpha}$ respectively, in developing thymocytes and peripheral T cells. The expression levels of transgenic proteins were 5-10 times higher than that of endogenous CD4 in thymus. However, total surface CD4 expression (CD4 or CD4{CD8${\alpha}$ transgenic protein plus endogenous CD4) of the transgenic mice were main. tained at similar levels compared to control littermates. Surface CD4 expression on CDS T cells, however, was significantly lower than that on cells expressing endogenous CD4. These results suggest that a total avidity between developing thymocytes and thymic stromal cells is impor. tant for differentiation of thymocytes.

• Journal of Periodontal and Implant Science
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• v.34 no.3
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• pp.489-498
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• 2004

Recent studies have demonstrated that human periodontal ligament cells express receptor activation of nuclear factor ${\kappa}B$ ligand (RANKL) which enhances the bone resorbing activity of osteoclasts differentiated from hematopoietic preosteoclasts. The purpose of this study is to determine the effects of p38 MAPK and JNK kinase upon regulating RANKL and OPG in response to $IL-1{\beta}$(l ng/ml) in rat periodontal ligament cells. Soluble RANKL was measured by immunoassay. The effects of p38 MAPK on RANKL and OPG expression was determined by RT-PCR. The results were as follows: 1. Periodontal ligament cells which stimulated by $IL-1{\beta}$ increased soluble RANKL synthesis by dose-dependent pattern. 2. p38 MAP kinase inhibitor (SB203580) showed regulation of soluble RANKL expression by dose-dependent manners. 3. p38 MAP kinase inhibitor (SB203580) regulated the expression of RANKL, but it dose regulate the expresseion of OPG. 4. JNK (c-jun $NH_2-terminal$ kinase) inhibitor (PD98059) did not regulate mRANKL and mOPG. These results suggested that p38 MAPK play a significant role in RANKL gene expression.

• Journal of Periodontal and Implant Science
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• v.32 no.4
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• pp.721-731
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• 2002

Recently, soluble TNF receptor homolog osteoprotegerin(OPG) and its membrane-bound ligand osteoclast differentiation factor(ODF) were found to regulate osteoclast formation and function, and bone metabolism. It is now well established that ODF acts via RANK expressed on hematopoietic osteoclast precursor cells to facilitate their differentiation to osteoclasts, and OPG prevents the formation of osteoclasts by interfering the binding of ODF and RANK. Expression of OPG and ODF was believed to be closely related to the pathogenesis of bone resorption and destruction from osteoporosis, periodontal diseases, malignant bone tumor, and arthritis. The periodontal ligament fibroblasts (PDLF), located between the tooth and tooth socket, has been thought to play an important role in maintaining bone homeostasis of periodontal tissues. However, the exact mechanism by which bone formation and resorption are regulated by PDLF is not well understood. In this study we have prepared primary cultures of human PDLF from periodontium of malaligned tooth extracted due to orthodontic reason, and determined steady state or inflammatory signal-induced OPG and ODF expression using RT-PCR and western blot analysis. OPG and ODF mRNA and protein were expressed constitutively in the PDLF and these expression were slightly increased by osteotropic cytokine IL-1 ${\beta}$. Lipopolysaccharide-treated PDLF showed decrease in OPG mRNA and protein expression, and increase in ODF mRNA and protein expression. These results indicated that PDLF influence the osteoclastogenesis by OPG and ODF expression in the inflammatory situation as well as physiological condition, and thereby pathogenesis of periodontal alveolar bone destruction.

• Journal of Life Science
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• v.19 no.2
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• pp.249-255
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• 2009

Esculetin, a coumarin compound, has been known to inhibit proliferation and induce apoptosis in several types of human cancer cells. However, the molecular mechanisms involved in esculetin-induced apoptosis are still uncharacterized in human leukemia cells. In this study, we have investigated whether esculetin exerts anti-proliferative and apoptotic effects on human leukemia U937 cells. It was found that esculetin could inhibit cell viability in a time-dependent manner, which was associated with the induction of apoptotic cell death such as increased populations of apoptotic- sub G1 phase. Apoptosis of U937 cells by esculetin was associated with an inhibition of Bcl-2/Bax binding activity, formation of tBid, down-regulation of X-linked inhibitor of apoptotic protein (XIAP) expression, and up-regulation of death receptor 4 (DR4) and FasL expression. Esculetin treatment also induced the degradation of ${\beta}$-catenin and DNA fragmentation factor 45/inhibitor of caspase-activated DNase (DFF45/ICAD). Furthermore, a caspase-3 specific inhibitor, z-DEVD-fmk, significantly inhibited sub-G1 phase DNA content, morphological changes and degradation of ${\beta}$-catenin and DEE45/ICAD. These results indicated that a key regulator in esculetin-induced apoptosis was caspase-3 in human leukemia U937 cells.