• Genomics & Informatics
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• v.4 no.4
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• pp.161-166
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• 2006

The establishment of DNA microarray technology has enabled high-throughput analysis and molecular profiling of various types of cancers. By using the gene expression data from microarray analysis we are able to investigate diagnostic applications at the molecular level. The most important step in the application of microarray technology to cancer diagnostics is the selection of specific markers from gene expression profiles. In order to select markers of Immortalization and transformation we used c-myc and $H-ras^{V12}$ oncogene-transfected NIH3T3 cells as our model system. We have identified 8751 differentially expressed genes in the immortalization/transformation model by multivariate permutation F-test (95% confidence, FDR<0.01). Using the support vector machine algorithm, we selected 13 discriminative genes which could be used to predict immortalization and transformation with perfect accuracy. We assayed $H-ras^{V12}$-transfected 'transformed' cells to validate our immortalization/transformation dassification system. The selected molecular markers generated valuable additional information for tumor diagnosis, prognosis and therapy development.

• Clinical and Experimental Pediatrics
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• v.60 no.11
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• pp.359-364
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• 2017

Purpose: The risk of cardiovascular disease (CVD) has been shown to be associated with systemic inflammation in obese adults with metabolic syndrome (MetS). The aims of this study were to evaluate the prevalence of MetS and its relation to inflammatory markers in obese Thai children. Methods: A cross-sectional study was conducted. Children with history of endogenous obesity, chronic diseases, drug ingestion, and any acute illness within 2 weeks prior to enrollment were excluded. Their fasting blood glucose (FBG) levels, oral glucose tolerance tests, insulin, lipid profiles, and selected inflammatory markers, including interleukin-6, tumor necrosis factor-alpha, and high-sensitivity C-reactive protein (hs-CRP) levels, were tested. Results: In this study, 58 obese Thai children (female, 20; male, 38) with a mean body mass index z score of $5.1{\pm}2.2$ were enrolled. The prevalence of MetS and prediabetes was 31% and 17.2%, respectively. None of the children had diabetes. FBG levels, 2-hour glucose levels, and lipid profiles were not statistically different between those with and without MetS. However, obese children with MetS had higher insulin levels and homeostasis model assessment of insulin resistance values. Elevated hs-CRP levels were found in 69% of the cases, although it was not statistically different between the 2 groups. Conclusion: We described a substantial prevalence of MetS in Thai obese children. Regardless of MetS status, two-thirds of the obese children had elevated hs-CRP level, indicating subtle ongoing inflammatory process. This chronic inflammation feasibly predisposes them to CVD in the future, even in children without MetS.

• Journal of Ginseng Research
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• v.44 no.4
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• pp.593-602
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• 2020

Background: Heat stress orchestrates neurodegenerative disorders and results in the formation of reactive oxygen species that leads to cell death. Although the immunomodulatory effects of ginseng are well studied, the mechanism by which ginseng alleviates heat stress in the brain remains elusive. Methods: Rats were exposed to intermittent heat stress for 6 months, and brain samples were examined to elucidate survival and antiinflammatory effect after Korean Red Ginseng (KRG) treatment. Results: Intermittent long-term heat stress (ILTHS) upregulated the expression of cyclooxygenase 2 and inducible nitric oxide synthase, increasing infiltration of inflammatory cells (hematoxylin and eosin staining) and the level of proinflammatory cytokines [tumor necrosis factor α, interferon gamma (IFN-γ), interleukin (IL)-1β, IL-6], leading to cell death (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay) and elevated markers of oxidative stress damage (myeloperoxidase and malondialdehyde), resulting in the downregulation of antiapoptotic markers (Bcl-2 and Bcl-x_L) and expression of estrogen receptor beta and brain-derived neurotrophic factor, key factors in regulating neuronal cell survival. In contrast, KRG mitigated ILTHS-induced release of proinflammatory mediators, upregulated the mRNA level of the antiinflammatory cytokine IL-10, and increased myeloperoxidase and malondialdehyde levels. In addition, KRG significantly decreased the expression of the proapoptotic marker (Bax), did not affect caspase-3 expression, but increased the expression of antiapoptotic markers (Bcl-2 and Bcl-x_L). Furthermore, KRG significantly activated the expression of both estrogen receptor beta and brain-derived neurotrophic factor. Conclusion: ILTHS induced oxidative stress responses and inflammatory molecules, which can lead to impaired neurogenesis and ultimately neuronal death, whereas, KRG, being the antioxidant, inhibited neuronal damage and increased cell viability.

• Nutrition Research and Practice
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• v.11 no.4
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• pp.290-299
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• 2017

BACKGROUND/OBJECTIVES: Spirulina is a known a functional food related to lipid profiles, immune functions, and antioxidant capacity. Circulating monocyte chemoattractant protein-1 (MCP-1) level is associated with inflammation markers. Single nucleotide polymorphism in the MCP-1 promoter region -2518 have been identified and shown to affect gene transcription. Gene variation may also impact functional food supplementary effects. The current study investigated the interaction of MCP-1 -2518 polymorphism with spirulina supplements on anti-inflammatory capacity in Korean elderly. SUBJECTS/METHODS: After genotyping, healthy elderly subjects (n = 78) were included in a randomized, double blind, and placebo controlled study. Baseline characteristic, body composition, and dietary intake were measured twice (baseline vs. week 16). For 16 weeks, subjects consumed 8 g either spirulina or placebo daily. Plasma MCP-1, interleukin (IL) -2, IL-6, tumor necrosis factor (TNF)-${\alpha}$, complement (C) 3, immunoglobulin (Ig) G, and Ig A concentrations and lymphocyte proliferation rate (LPR) were analyzed as inflammatory markers. RESULTS: In the placebo group with A/A genotype, MCP-1 level was significantly increased, but the spirulina group with A/A genotype was unchanged. IL-2 was significantly increased only in subjects with spirulina supplementation. TNF-${\alpha}$ was significantly reduced in subjects with the G carrier. C3 was significantly increased in the placebo group, particularly when A/A increased more than G, but not when spirulina was ingested. LPR was significantly different only in subjects with A/A genotype; there was a significant increase in phytohemagglutinin and lipopolysaccharide induced LPR in the spirulina group. CONCLUSION: In healthy Korean elderly, spirulina supplementation may influence different inflammatory markers by the MCP-1 genotype. These results may be useful for customized dietary guidelines to improve immune function in Koreans.

• Animal Bioscience
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• v.36 no.10
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• pp.1578-1583
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• 2023

Objective: This study was conducted to evaluate the effects of vitamin K (VK) supplementation on reproductive performance and bone metabolism-related biochemical markers in sows. Methods: Twenty-four Large White×Landrace sows (mean parity 4.04) were randomly assigned to two dietary treatments (NC diet, a basal diet with 0.5 mg/kg of VK₃; VK diet, a basal diet with 5 mg/kg of VK₃) with twelve replicates per treatment and one sow per replicate according to parity. The experiment started on day 107 of gestation and lasted until day 21 of lactation (weaning). Results: We observed that there were no differences (p>0.05) in average daily feed intake, backfat loss of sows, live piglet number at birth and weaning, average birth weight, average weaning weight, and average daily gain of piglets between two treatments. The apparent total tract digestibility of phosphorus was increased (p<0.05) in VK sows compared with NC sows. The serum bone alkaline phosphatase, osteocalcin, type I procollagen amino-terminal peptide, and type I procollagen carboxyl-terminal peptide on day of farrowing were higher (p<0.05) in VK sows than in NC sows. The serum phosphorus, parathyroid hormone, tartrate-resistant acid phosphatase, and tumor necrosis factor-alpha on day of weaning were lower (p<0.05) in VK sows compared with NC sows. Conclusion: Therefore, the overall results suggested that increasing dietary VK₃ (0.5 to 5 mg/kg) during lactation improved the apparent total tract digestibility of phosphorus and serum bone metabolism biochemical markers in sows.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.3
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• pp.209-217
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• 2008

Purpose: To date, anatomical imaging modalities of the pelvis and tumor markers have been the mainstay of surveillance for recurrent ovary cancer. This study aimed to assess the role of $^{18}F$-FDG PET/CT in evaluation of ovary cancer recurrences, especially in comparison with enhanced a and tumor marker CA 125. Materials and methods: 73 patients who had PET/CT scan for restaging of confirmed ovary cancer, and additional imaging with enhanced a of the pelvis within one month were included. CA 125 level was available in all patients. From the PET/CT images, maximum standard uptake values (SUVmax) of suspected recurrence sites were recorded. Confirmation was available through re-operation or biopsy in 26 cases, and clinical assessment with series of follow-up images in 47. Results: PET/CT had 93% sensitivity and 88% specificity for detecting recurrent ovary cancer. Enhanced a of pelvis had sensitivity and specificity of 83% and 88%, and CA 125 50% and 95%. Conclusion: PET/CT has higher sensitivity for detecting recurrent ovary cancer compared to enhanced a though the differences were not significant. PET/CT has significantly higher sensitivity than CA 125. However, the three tests all agreed in only 43% of the recurrence cases, and recurrence should be suspected when any of the tests, especially PET/CT, show positive findings.

• Radiation Oncology Journal
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• v.34 no.3
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• pp.223-229
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• 2016

Purpose: This study is to investigate the effect of captopril when combined with irradiation. Materials and Methods: 4T1 (mouse mammary carcinoma) cells were injected in the right hind leg of Balb/c mice. Mice were randomized to four groups; control (group 1), captopril-treated (group 2), irradiated (group 3), irradiated and captopril-treated concurrently (group 4). Captopril was administered by intraperitoneal injection (10 mg/kg) daily and irradiation was delivered on the tumor-bearing leg for 15 Gy in 3 fractions. Surface markers of splenic neutrophils (G-MDSCs) and intratumoral neutrophils (tumor-associated neutrophils [TANs]) were assessed using flow cytometry and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha ($HIF-1{\alpha}$) of tumor was evaluated by immunohistochemical (IHC) staining. Results: The mean tumor volumes (${\pm}$standard error) at the 15th day after randomization were $1,382.0({\pm}201.2)mm^3$ (group 1), $559.9({\pm}67.8)mm^3$ (group 3), and $370.5({\pm}48.1)mm^3$ (group 4), respectively. For G-MDSCs, irradiation reversed decreased expression of CD101 from tumor-bearing mice, and additional increase of CD101 expression was induced by captopril administration. Similar tendency was observed in TANs. The expression of tumor-necrosis factor-associated molecules, CD120 and CD137, are increased by irradiation in both G-MDSCs and TANs. Further increment was observed by captopril except CD120 in TANs. For IHC staining, VEGF and $HIF-1{\alpha}$ positivity in tumor cells were decreased when treated with captopril. Conclusion: Captopril is suggested to have additional effect when combined to irradiation in a murine tumor model by modulation of MDSCs and angiogenesis.

• Journal of Gastric Cancer
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• v.4 no.2
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• pp.109-120
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• 2004

Purpose: Individual gastric cancers demonstrate complicated genetic alterations. The PCR-based analysis of polymorphic microsatellite sequences on cancer-related chromosomes has been used to detect chromosomal loss and microsatellite instability. For the purpose of preoperative usage, we analyzed the correspondance rate of the microsatellite genotype between endoscopic biopsy and surgical specimens. Materials and Methods: Seventy-three pairs of biopsy and surgical specimens were examined for loss of heterozygosity and microsatellite instability by using 40 microsatellite markers on eight chromosomes. Microsatellite alterations in tumor DNAs were classified into a high-risk group (baselinelevel loss of heterozygosity: 1 chromosomal loss in diffuse type and high-level loss of heterozygosity: 4 or more chromosomal losses) and a low-risk group (microsatellite instability and low-level loss of heterozygosity: 2 or 3 chromosomal losses in diffuse type or $1\∼3$ chromosomal losses in intestinal type) based on the extent of chromosomal loss and microsatellite instability. Results: The chromosomal losses of the biopsy and the surgical specimens were found to be different in 21 of the 73 cases, 19 cases of which were categorized into a genotype group of similar extent. In 100 surgical specimens, the high-risk genotype group showed a high incidence of nodal involvement (19 of 23 cases: $\leq$5 cm; 23 of 24 cases: >5 cm) irrespective of tumor size while the incidence of nodal involvement for the low-risk genotype group depended on tumor size (5 of 26 cases: $\leq$5 cm; 18 of 27 cases: >5 cm). Extraserosal invasion was more frequent in large-sized tumor in both the high-risk genotype group ($\leq$5 cm: 12 of 23 cases; >5 cm: 23 of 24 cases) and the low-risk genotype group ($\leq$5 cm: 7 of 26 cases; >5 cm: 16 of 27 cases). The preoperative prediction of tumor invasion and nodal involvement based on tumor size and genotype corresponded closely to the pathologic tumor stage (ROC area >0.7). Conclusion: An endoscopic biopsy specimen of gastric cancer can be used to make a preoperative genetic diagnosis that accurately reflect the genotype of the corresponding surgical specimen.

• BMB Reports
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• v.55 no.2
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• pp.81-86
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• 2022

Macrophages are a major cellular component of innate immunity and are mainly known to have phagocytic activity. In the tumor microenvironment (TME), they can be differentiated into tumor-associated macrophages (TAMs). As the most abundant immune cells in the TME, TAMs promote tumor progression by enhancing angiogenesis, suppressing T cells and increasing immunosuppressive cytokine production. N-myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor gene, whose expression is down-regulated in various cancers. However, the effect of NDRG2 on the differentiation of macrophages into TAMs in breast cancer remains elusive. In this study, we investigated the effect of NDRG2 expression in breast cancer cells on the differentiation of macrophages into TAMs. Compared to tumor cell-conditioned medium (TCCM) from 4T1-mock cells, TCCM from NDRG2-over-expressing 4T1 mouse breast cancer cells did not significantly change the morphology of RAW 264.7 cells. However, TCCM from 4T1-NDRG2 cells reduced the mRNA levels of TAM-related genes, including MR1, IL-10, ARG1 and iNOS, in RAW 264.7 cells. In addition, TCCM from 4T1-NDRG2 cells reduced the expression of TAM-related surface markers, such as CD206, in peritoneal macrophages (PEM). The mRNA expression of TAM-related genes, including IL-10, YM1, FIZZ1, MR1, ARG1 and iNOS, was also downregulated by TCCM from 4T1-NDRG2 cells. Remarkably, TCCM from 4T1-NDRG2 cells reduced the expression of PD-L1 and Fra-1 as well as the production of GM-CSF, IL-10 and ROS, leading to the attenuation of T cell-inhibitory activity of PEM. These data showed that compared with TCCM from 4T1-mock cells, TCCM from 4T1-NDRG2 cells suppressed the TAM differentiation and activation. Collectively, these results suggest that NDRG2 expression in breast cancer may reduce the differentiation of macrophages into TAMs in the TME.

• Journal of Periodontal and Implant Science
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• v.34 no.3
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• pp.607-622
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• 2004

Recently epidemiologic studies have indicated that the patients with periodontitis may have increased risk of ischemic cardiovascular events, and have suggested the important roles of blood cytokines and acute reactant proteins in the systemic infection and inflammatory response. Periodontitis and coronary heart disease (CHD) may share the common risk factors and the genetic mechanism associated with interleukin(IL)-1A, B and RA genotype may be involved in the production of IL-1. This study was aimed to investigate the relationship between angiographically defined CHD and periodontitis as chronic Gram-negative bacterial infection and to determine whether the IL-1 gene polymorphism is associated in both diseases. Patients under the age of 60 who had undergone diagnostic coronary angiography were enrolled in this study. Subjects were classified as positive CHD (+CHD, n=37) with coronary artery stenosis more than 50% in at least one of major epicardial arteries, and negative CHD (-CHD, n=30) without significant stenosis. After recording the number of missing teeth, periodontal disease severity was measured by means of plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), and radiographic bone loss around all remaining teeth. Gingival crevicular fluid (GCF) was collected from the 4 deepest periodontal pockets and assessed for cytokine ($IL-1{\beta}$, IL-6, IL-1ra, tumor necrosis $factor-{\alpha}$, and prostaglandin $E_2$). Additionally, blood CHD markers, lipid profile, and blood cytokines were analyzed. IL-1 gene cluster genotyping was performed by polymerase chain reaction and enzyme restriction using genomic DNA from buccal swab, and allele 2 frequencies of IL-1A(+4845), IL-1B(+3954), IL-B(-511), and IL-1RA(intron 2) were compared between groups. Even though there was no significant difference in the periodontal parameters between 2 groups, GCF level of $PGE_2$ was significantly higher in the +CHD group(p<0.05). Correlation analysis showed the positive relationship among PD, CAL and coronary artery stenosis(%) and blood $PGE_2$. There was also significant positive relationship between the periodontal parameters (PI, PD, CAL) and the blood CHD markers (leukocyte count, C-reactive protein, and lactic dehyrogenase). IL-1 gene genotyping showed that IL-1A(+3954) allele 2 frequency was significantly higher in the +CHD group compared with the -CHD group (15% vs. 3.3%, OR 5.118,p=0.043). These results suggested that periodontal inflammation is related to systemic blood cytokine and CHD markers, and contributes to cardiovascular disease via systemic inflammatory reaction. IL-1 gene polymorphism might have an influence on periodontal and coronary heart diseases in Korean patients.