• Title/Summary/Keyword: Tissue microarray

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Comparative Gene-Expression Analysis of Periodontal Ligament and Dental Pulp in the Human Permanent Teeth (사람 영구치에서 치주인대 및 치수 조직의 유전자 발현에 대한 비교 연구)

  • Lee, Suk Woo;Jeon, Mijeong;Lee, Hyo-Seol;Song, Je Seon;Son, Heung-Kyu;Choi, Hyung-Jun;Jung, Han-Sung;Moon, Seok-Jun;Park, Wonse;Kim, Seong-Oh
    • Journal of the korean academy of Pediatric Dentistry
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    • v.43 no.2
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    • pp.166-175
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    • 2016
  • There is no genetic activity information with the functions of dental pulp and periodontal ligament in human. The purpose of this study was to identify the gene-expression profiles of, and the molecular biological differences between periodontal ligament and dental pulp obtained from human permanent teeth. cDNA microarray analysis identified 347 genes with a fourfold or greater difference in expression level between the two tissue types 83 and 264, of which were more plentiful in periodontal ligament and dental pulp, respectively. Periodontal ligament exhibited strong expression of genes related to collagen synthesis (FAP), collagen degradation (MMP3, MMP9, and MMP13), and bone development and remodeling (SSP1, BMP3, ACP5, CTSK, and PTHLH). Pulp exhibited strong expression of genes associated with calcium ions (CALB1, SCIN, and CDH12) and the mineralization and formation of enamel and dentin (SPARC/SPOCK3, PHEX, AMBN, and DSPP). Among these genes, SPP1, SPARC/SPOCK3, AMBN, and DSPP were well known in dental research. However, the other genes are the newly found and it may help to find a good source of regenerative therapy if further study is performed.

Application of Differential Expression of Genetic Profiles in Brain Tumors with Variable [$^{18}F$]-fluorodeoxyglucose Uptake

  • Lee, Seung-Ho;Yun, Mi-Jin;Kim, Ki-Nam;Seo, Sang-Hui;Sohn, Sung-Hwa;Kim, Yu-Ri;Kim, Hye-Won;Kim, In-Kyoung;Shim, Boo-Im;Lee, Seung-Min;Kim, Meyoung-Kon
    • Molecular & Cellular Toxicology
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    • v.3 no.3
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    • pp.198-207
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    • 2007
  • [ $^{18}F$ ]-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan has been found to reflect tumor aggressiveness and prognosis in various types of cancer. In this study, the gene expression profiles of glial tumors were evaluated to determine whether glial tumors with high $^{18}F$-FDG uptake have more aggressive biological potential than with low uptake. Surgical specimens were obtained from the 12 patients with glial tumors (4 males and 8 females, age range 42-68 years). The tumor samples were divided into two groups based on the $^{18}F$-FDG uptake PET scan findings: high $^{18}F$-FDG uptake (n=4) and low $^{18}F$-FDG uptake (n=8). The pathological tumor grade was closely correlated with the $^{18}F$-FDG uptake pattern: Glial tumors with high $^{18}F$-FDG uptake were pathologically Edmondson-Steiner grade III, while those with low uptake were grade II. The total RNA was extracted from the frozen tissues of all glial tumors (n=12), and adjacent non-cancerous tissue (n=3). The gene expression profiles were evaluated using cDNA microarray. The glial tumors with high $^{18}F$-FDG uptake showed increase expression of 15 genes compared to those with low uptake (P<0.005). Nine genes were down-regulated. Gene expression is closely related to cell survival, cell-to-cell adhesion or cell spreading; therefore, glial tumors with high $^{18}F$-FDG uptake appear to have more aggressive biological properties than those with low uptake.

Expression Levels of GABA-A Receptor Subunit Alpha 3, Gabra3 and Lipoprotein Lipase, Lpl Are Associated with the Susceptibility to Acetaminophen-Induced Hepatotoxicity

  • Kim, Minjeong;Yun, Jun-Won;Shin, Kyeho;Cho, Yejin;Yang, Mijeong;Nam, Ki Taek;Lim, Kyung-Min
    • Biomolecules & Therapeutics
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    • v.25 no.2
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    • pp.112-121
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    • 2017
  • Drug-induced liver injury (DILI) is the serious and fatal drug-associated adverse effect, but its incidence is very low and individual variation in severity is substantial. Acetaminophen (APAP)-induced liver injury accounts for >50% of reported DILI cases but little is known for the cause of individual variations in the severity. Intrinsic genetic variation is considered a key element but the identity of the genes was not well-established. Here, pre-biopsy method and microarray technique was applied to uncover the key genes for APAP-induced liver injury in mice, and a cause and effect experiment employing quantitative real-time PCR was conducted to confirm the correlation between the uncovered genes and APAP-induced hepatotoxicity. We identified the innately and differentially expressed genes of mice susceptible to APAP-induced hepatotoxicity in the pre-biopsied liver tissue before APAP treatment through microarray analysis of the global gene expression profiles (Affymetrix $GeneChip^{(R)}$ Mouse Gene 1.0 ST for 28,853 genes). Expression of 16 genes including Gdap10, Lpl, Gabra3 and Ccrn4l were significantly different (t-test: FDR <10%) more than 1.5 fold in the susceptible animals than resistant. To confirm the association with the susceptibility to APAP-induced hepatotoxicity, another set of animals were measured for the expression level of selected 4 genes (higher two and lower two genes) in the liver pre-biopsy and their sensitivity to APAP-induced hepatotoxicity was evaluated by post hoc. Notably, the expressions of Gabra3 and Lpl were significantly correlated with the severity of liver injury (p<0.05) demonstrating that these genes may be linked to the susceptibility to APAP-induced hepatotoxicity.

MicroRNA Expression Profiling in Cell and Mouse Models of Fabry Disease to Identify Biomarkers for Fabry Disease Nephropathy (파브리병의 바이오마커 발굴을 위한 파브리 마우스와 세포모델에서의 microRNA 발현 분석)

  • Jung, Namhee;Park, Saeyoung;Jeon, Yeo Jin;Choi, Yoonyoung;Jung, Sung-Chul
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.15 no.3
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    • pp.127-137
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    • 2015
  • Purpose: The main aim of this study was to compare and analyze expression profiles of microRNAs (miRNAs) to establish miRNA signature of Fabry nephropathy related epithelial mesenchymal transition (EMT). Methods: Expression profiles of miRNAs in kidney tissue samples and cell lines from normal and Fabry disease mouse model were examined by miRNA expression microarray analysis followed by quantitative real-time polymerase chain reaction analysis (qRT-PCR). Results: In the miRNA expression microarray analysis of Fabry mouse kidney tissues compared to wild type mouse, 5 and 3 miRNAs among 1,247 miRNAs examined were up- and down-regulated, respectively. Among them, miR-149-5p was down-regulated about 2-fold in Fabry kidney samples. The down-regulations of miR-149-5p were observed in kidney tissues of under 35 week-old-Fabry mice. However, this down-regulation was not observed in kidney tissues of 42 week-old Fabry mice. In SV40 MES 13 cells, mouse mesangial cells, treated with globotriaosylsphingosine (lyso-Gb3), miR-149-5p was also downregulated. The down-regulation of miR-149-5p induced up-regulation of its target genes related to EMT. Conclusion: The miRNA expression array and qRT-PCR results show that miR-149-5p expression was decreased in kidney tissues of Fabry mice compared to wild type mice under 35 weeks of age. Along with the observation of miR-149-5p expression in Fabry disease cell models, these results indicate that the down-regulated miR-149-5p were related to the biological response of mesangial cells to lyso-Gb3 and also have influence to the transcriptional up-regulation of its target genes. These results suggest miR-149-5p might play important roles in the Fabry nephropathy.

Low Expression of the FoxO4 Gene may Contribute to the Phenomenon of EMT in Non-small Cell Lung Cancer

  • Xu, Ming-Ming;Mao, Guo-Xin;Liu, Jian;Li, Jian-Chao;Huang, Hua;Liu, Yi-Fei;Liu, Jun-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.9
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    • pp.4013-4018
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    • 2014
  • Because of its importance in tumor invasion and metastasis, the epithelial-mesenchymal transition (EMT) has become a research focus in the field of cancer. Recently, evidence has been presented that FoxO4 might be involved in EMT. Our study aimed to detect the expression of FoxO4, E-cadherin and vimentin in non-small cell lung cancers (NSCLCs). We also investigated clinical features and their correlations with the markers. In our study, FoxO4, E-cadherin and vimentin were assessed by immunohistochemistry in a tissue microarray (TMA) containing 150 cases of NSCLC. In addition, the expression level of FoxO4 protein was determined by Western blotting. The percentages of FoxO4, E-cadherin and vimentin positive expression in NSCLCs were 42.7%, 38.7% and 55.3%, respectively. Immunoreactivity of FoxO4 was low in NSCLC when compared with paired normal lung tissues. There were significant correlations between FoxO4 and TNM stage (P<0.001), histological differentiation (P=0.004) and lymph node metastasis (P<0.001), but no significant links with age (P=0.323), gender (P=0.410), tumor size (P=0.084), smoking status (P=0.721) and histological type (P=0.281). Our study showed that low expression of FoxO4 correlated with decreased expression of E-cadherin and elevated expression of vimentin. Cox regression analysis indicated FoxO4 to be an independent prognostic factor in NSCLC (P=0.046). These data suggested that FoxO4 might inhibit the process of EMT in NSCLC, and might therefore be a target for therapy.

Expression Analysis of miRNAs in Porcine Fetal Skeletal Muscle on Days 65 and 90 of Gestation

  • Chen, Jian-hai;Wei, Wen-Juan;Xiao, Xiao;Zhu, Meng-Jin;Fan, Bin;Zhao, Shu-Hong
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.7
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    • pp.954-960
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    • 2008
  • MiRNAs (microRNAs) are a class of small non-coding RNA molecules of ~21 nucleotides that down- regulate the expression of target genes at post-transcriptional level. In this study, we first accomplished a preliminary scan of miRNA expression using 65 and 90 day fetal pig skeletal muscle samples by microarray hybridization, and 34 miRNAs showed strong positive signals. Five of these miRNAs were selected for further investigation by real-time RT-PCR. The statistical analyses indicated that three miRNAs exhibited significant differential expression (p<0.05) during porcine muscle development from 65 to 90 days of gestation, e.g., miR-24 and miR-424 were down-regulated while miR-133a was up-regulated. Multi-tissue RT-PCR was performed to detect the expression patterns of the five miRNA precursors. The results showed that most of these precursor miRNAs were ubiquitously expressed in different porcine tissues.

Classifying Cancer Using Partially Correlated Genes Selected by Forward Selection Method (전진선택법에 의해 선택된 부분 상관관계의 유전자들을 이용한 암 분류)

  • 유시호;조성배
    • Journal of the Institute of Electronics Engineers of Korea SP
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    • v.41 no.3
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    • pp.83-92
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    • 2004
  • Gene expression profile is numerical data of gene expression level from organism measured on the microarray. Generally, each specific tissue indicates different expression levels in related genes, so that we can classify cancer with gene expression profile. Because not all the genes are related to classification, it is needed to select related genes that is called feature selection. This paper proposes a new gene selection method using forward selection method in regression analysis. This method reduces redundant information in the selected genes to have more efficient classification. We used k-nearest neighbor as a classifier and tested with colon cancer dataset. The results are compared with Pearson's coefficient and Spearman's coefficient methods and the proposed method showed better performance. It showed 90.3% accuracy in classification. The method also successfully applied to lymphoma cancer dataset.

Co-Expression of Putative Cancer Stem Cell Markers, CD133 and Nestin, in Skin Tumors

  • Sabet, Mehrdad Nasrollahzadeh;Rakhshan, Azadeh;Erfani, Elham;Madjd, Zahra
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8161-8169
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    • 2014
  • Background: Cancer stem cells (CSC) are populations of cells responsible for tumor initiation, progression and therapeutic resistance in many cancers. In the present study, we aimed to investigate the expression pattern and clinical significance of two CSC markers, CD133 and Nestin, in a series of skin tumors. Materials and Methods: One hundred and thirteen paraffin blocks from skin cancers including 16 (14%) cases of melanoma, 37 (33%) of squamous cell cancer (SCC) and 60 (53%) of basal cell cancer (BCC) were collected and assembled in a tissue microarray (TMA). The samples were immunohistochemically examined for the expression of CD133 and Nestin. Expression of these markers was also correlated with clinicopathological parameters. Results: A significant difference was observed in the expression of CD133 and Nestin in melanomas, SCC and BCC (p value=0.001). Furthermore, the level of expression was significantly higher in the melanomas compared to the SCC and BCC tumors. Expression of CD133 in the melanoma was significantly associated with increased tumor invasiveness (p value=0.05), a higher rate of metastasis (p value=0.04) and the presence of ulceration (p value=0.02). Increased expression of Nestin was observed in metastatic melanoma (p value=0.04), while no statistically significant correlation was found with other clinicopathological parameters including Breslow thickness, Clark level and ulceration. Conclusions: Elevated expression levels of CD133 and Nestin in the melanomas are associated with advanced disease, with more aggressive and metastatic skin tumors. Therefore, these markers could be potential therapeutic targets for malignant tumors of the skin.

Gene Expression of Hyperthyroid Rats treated by Scrophularia buergeriana Miquel (현삼(玄蔘)이 갑상선기능항진증(甲狀腺機能亢進症) 유발(誘發) 흰쥐의 유전자(遺傳子) 발현(發顯)에 미치는 영향(影響))

  • Cho, Chung-Sik;Kim, Dae-Bok;Kim, Cheol-Jung
    • The Korea Journal of Herbology
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    • v.22 no.4
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    • pp.9-19
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    • 2007
  • Objective : The study was done to investigate Scrophularia buergeriana Miquel's effects in the genomic level, by measuring gene expression in hyperthyroid induced rats using cDNA micro array. Methods : Spargue-Dawley rats were separated into three groups(each with 10 rats). Except normal group, the other two groups were treated with Sodium levothyroxine $160{\mu}g$/kg/days for 5 days by oral administration. After 2 hours of the last intake of Sodium levothyroxine on two experimental group, one group was treated Scrophularia buergeriana Miquel extract 1.0g/kg/days for 3 days. The other groups(normal group, administration group) was treated normal saline 1.0g/kg/days for 3 days. Gene expression of hyperthyroid rats were measured after medication of solid extract of Scrophularia buergeriana Miquel with cDNA microarray. Results : In thyroid tissue, the numbers of the genes showed over twice increase and decrease in the control group compared to the normal group were 296, in the Scrophularia buergeriana Miquel administration group compared to the normal group were 859 and in the hypothalamus, the numbers of the genes showed over twice increase and decrease in the control group compared to the normal group were 416, in the Scrophularia buergeriana Miquel administration group compared to the normal group were 391. Conclusion : According to the above results, it is suggested that Scrophulari buergeriana Miquel suppress hyperthyroidism effectively and regulate the gene expression in the thyroid and brain.

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Immunohistochemical Expression and Prognostic Value of VEGF, HIF-$1{\alpha}$, EGFR in Non-Small Cell Lung Cancer (비소세포 폐암에서 VEGF, HIF-$1{\alpha}$, EGFR의 면역조직화학적 발현과 예후 인자로서의 역할)

  • Kim, Myung-Sook;Park, Sung-Hak
    • Tuberculosis and Respiratory Diseases
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    • v.68 no.1
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    • pp.22-28
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    • 2010
  • Background: Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis. VEGF production is regulated by HIF-$1{\alpha}$ and EGFR. This study examined the relationship between the clinicopathological factors and VEGF, HIF-$1{\alpha}$ and EGFR protein overexpression, and evaluated their prognostic value in patients with a surgically resected non-small cell lung cancer (NSCLC). Methods: Patients who underwent a surgical resection at Kangnam St. Mary's hospital were reviewed retrospectively. The core biopsy samples from 54 patients with NSCLC were assembled on a tissue microarray (TMA), and immunohistochemical staining for the VEGF, HIF-$1{\alpha}$ and EGFR proteins was performed. The overexpression of these proteins was evaluated in relation to age, gender, histology and staging by univariate analysis. The clinicopathological prognostic factors were analyzed. Results: Multivariate analysis performed by Cox regression (odds ratio 2.8, 95% CI 1.0~8.2, p=0.046) revealed HIF-$1{\alpha}$ overexpression to be an unfavorable factor. There was no correlation between the overexpression of these proteins and the clinicopathological factors. VEGF showed a positive relationship with EGFR, but there was no statistical significance [$p(x^2)=0.06$]. Conclusion: HIF-$1{\alpha}$ overexpression predicts shorter survival in patients with a surgically resected NSCLC. Therefore, HIF-$1{\alpha}$ may be a poor prognostic factor in NSCLC.