• Molecular & Cellular Toxicology
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• v.1 no.2
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• pp.78-86
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• 2005

Dioxins, especially 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin), are ubiquitous environmental contaminants. TCDD is known that it has toxic effects in animals and humans, including chloracne, immune, reproductive and developmental toxicities, carcinogenicity, wasting syndrome and death. TCDD induces a broad spectrum of biological responses, including disruption of normal hormone signaling pathways, reproductive and developmental defects, immunotoxicity, liver damage, wasting syndrome and cancer. Many researches showed that TCDD induces gene expression of transcriptional factors related cell proliferation, signal transduction, immune system and cell cycle arrest at molecular and cellular levels. These toxic actions of TCDD are usually mediated with AhR (receptor, resulted from cell culture, animal and clinical studies). cDNA microarray can be used as a highly sensitive and informative marker for toxicity. Additionally, microarray analysis of dioxin-toxicity is able to provide an opportunity for the development of candidate bridging biomarkers of dioxin-toxicity. Through microarray technology, it is possible to understand the therapeutic effects of agonists within the context of toxic effects, classify new chemicals as to their complete effects on biological systems, and identify environmental factors that may influence safety.

• Journal of the Korean Data and Information Science Society
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• v.23 no.1
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• pp.1-11
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• 2012

When the microarray experiment developed, main interest was limited to detect differentially expressed genes associated with a phenotype of interest. However, as human diseases are thought to occur through the interactions of multiple genes within a same functional category, the unit of analysis of the microarray experiment expanded to the set of genes. For the phenotype of censored survival time, Gene Set Enrichment Analysis(GSEA), Global test and Wald type test are widely used. In this paper, we modified the Wald type test by adopting normal score transformation of gene expression values and developed a parametric test which requires much less computation than others. The proposed method is compared with other methods using a real data set of ovarian cancer and a simulation data set.

• Journal of Interdisciplinary Genomics
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• v.4 no.2
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• pp.31-34
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• 2022

Background: Arteriovenous malformations (AVMs) are rare diseases comprising abnormally dilated arteries and veins with an absence of a capillary network. Since these diseases are intractable after diagnosis, various treatment strategies have been examined, with continuous efforts to identify target genes. Here, we report relevant new target genes selected via gene microarray. Methods: Endothelial cells were isolated from samples collected from three patients with AVM and three healthy individuals, followed by microarray analysis. Additionally, quantitative PCR was performed to select genes highly relevant to AVM. Results: In the vascular endothelial cells derived from the tissues of patients with AVM, the expression of ANGPT1, ANGPT2, DLL4, IL6, NRG1, TGFBR1, and VEGFA was typically higher compared to those derived from normal tissues. Conclusion: Seven candidate genes were selected to analyze the pathophysiological mechanism of AVM. These results may aid in future directions of diagnosis and treatment.

• BMB Reports
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• v.35 no.4
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• pp.420-427
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• 2002

Partial nerve injury is the main cause of neuropathic pain disorders in humans. Acupuncture has long been used to relieve pain. It is known to relieve pain by controlling the activities of the autonomic nervous system. Although the mechanism of neuropathic pain and analgesic effects of electroacupuncture (EA) have been studied in a rat model system, its detailed mechanism at the molecular level remains unclear. To identify genes that might serve as either markers or explain these distinct biological functions, a cDNA microarray analysis was used to compare the expression of 8,400 genes among three sample groups. Messenger RNAs that were pooled from the spinal nerves of 7 normal. 7 neuropathic pain, and 7 EA treatment rat models were compared. Sixty-eight genes were differentially expressed more than 2-fold in the neuropathic rat model when compared to the normal, and restored to the normal expression level after the EA treatment. These genes are involved in a number of biological processes, including the signal transduction, gene expression, and nociceptive pathways. Confirmation of the differential gene expression was performed by a dot-blot analysis. Dot-blotting results showed that the opioid receptor sigma was among those genes. This indicates that opioid-signaling events are involved in neuropathic pain and the analgesic effects of EA. The potential application of these data include the identification and characterization of signaling pathways that are involved in the EA treatment, studies on the role of the opioid receptor in neuropathic pain, and further exploration on the role of selected identified genes in animal models.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4553-4557
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• 2013

Objective: The purpose of this study was to identify genes related to bladder cancer with samples from normal and disease cases by microarray chip. Methods: After downloading the gene expression profile GSE3167 from Gene Expression Omnibus database which includes 50 bladder samples, comprising 9 normal and 41 disease samples, differentially expressed genes were identified with packages in R language. The selected differentially expressed genes were further analyzed using bioinformatics methods. Firstly, molecular functions, biological processes and cell component analysis were researched by software Gestalt. Then, software String was used to search interaction relationships among differentially expressed genes, and hub genes of the network were selected. Finally, by using plugins of software Cytoscape, Mcode and Bingo, module analysis of hub-genes was performed. Results: A total of 221 genes were identified as differentially expressed by comparing normal and disease bladder samples, and a network as well as the hub gene C1QBP was obtained from the network. The C1QBP module had the closest relationship to production of molecular mediators involved in inflammatory responses. Conclusion: We obtained differentially expressed genes of bladder cancer by microarray, and both PRDX2 and YWHAZ in the module with hub gene C1QBP were most significantly related to production of molecular mediators involved in inflammatory responses. From knowledge of inflammatory responses and cancer, our results showed that, the hub gene and its module could induce inflammation in bladder cancer. These related genes are candidate bio-markers for bladder cancer diagnosis and might be helpful in designing novel therapies.

• Environmental Mutagens and Carcinogens
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• v.22 no.3
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• pp.142-148
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• 2002

Although ionizing radiation (IR) has been used to treat the various human cancers, IR is cytotoxic not only to cancer cells but to the adjacent normal tissue. Since normal tissue complications are the limiting factor of cancer radiotherapy, one of the major concerns of IR therapy is to maximize the cancer cell killing and to minimize the toxic side effects on the adjacent normal tissue. As an attempt to develop a method to monitor the degree of radiation exposure to normal tissues during radiotherapy, we investigated the transcriptional responses of human peripheral blood lymphocytes (PBL) following IR using cDNA microarray chip containing 1,221 (1.2 K) known genes. Since conventional radiotherapy is delivered at about 24 h intervals at 180 to 300 cGy/day, we analyzed the transcriptional responses ex-vivo irradiated human PBL at 200 cGy for 24 h-period. We observed and report on 1) a group of genes transiently induced early after IR at 2 h, 2) of genes induced after IR at 6 h, 3) of genes induced after IR at 24 h and on 4) a group of genes whose expression patters were not changed after IR. Since Biological consequences of IR involve generation of various reactive oxygen species (ROS) and thus oxidative stress induced by the ROS is known to damage normal tissues during radiotherapy, we further tested the temporal expression profiles of genes involved in ROS modulation by RT-PCR. Specific changes of 6 antioxidant genes were identified in irradiated PBL among 9 genes tested. Our results suggest the potential of monitoring post-radiotherapy changes in temporal expression profiles of a specific set of genes as a measure of radiation effects on normal tissues. This type of approach should yield more useful information when validated in in vivo irradiated PBL from the cancer patients.

• Genomics & Informatics
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• v.6 no.4
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• pp.210-222
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• 2008

Due to the polygenic nature of cancer, it is believed that breast cancer is caused by the perturbation of multiple genes and their complex interactions, which contribute to the wide aspects of disease phenotypes. A systems biology approach for the identification of subnetworks of interconnected genes as functional modules is required to understand the complex nature of diseases such as breast cancer. In this study, we apply a 3-step strategy for the interpretation of microarray data, focusing on identifying significantly perturbed metabolic pathways rather than analyzing a large amount of overexpressed and underexpressed individual genes. The selected pathways are considered to be dysregulated functional modules that putatively contribute to the progression of disease. The subnetwork of protein-protein interactions for these dysregulated pathways are constructed for further detailed analysis. We evaluated the method by analyzing microarray datasets of breast cancer tissues; i.e., normal and invasive breast cancer tissues. Using the strategy of microarray analysis, we selected several significantly perturbed pathways that are implicated in the regulation of progression of breast cancers, including the extracellular matrix-receptor interaction pathway and the focal adhesion pathway. Moreover, these selected pathways include several known breast cancer-related genes. It is concluded from this study that the present strategy is capable of selecting interesting perturbed pathways that putatively play a role in the progression of breast cancer and provides an improved interpretability of networks of protein-protein interactions.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.6
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• pp.1393-1403
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• 2003

The genetic effects of restraint stress challenge on HPA axis and the therapeutic effect of Boshimgeonbi-Tang on the stress were studied with cDNA microarray analyses on hypothalamus using an immobilization-stress mouse as stress model. Male CD-1 mice were restrained in a tightly fitted and ventilated vinyl holder for 2hours once a day, and this challenge was repeated for seven consecutive days. The body weights of the immobilization-stress mice were diminished about 25 percent degree as compared to normal ones. Seven days later, total RNA was extracted from the organs of the mouse, body-labeled with CyDye/sup TM/ fluorescence dyes (Amersham Bioscience Co., NJ), and then hybridized to cDNA microarray chip. Scanning and analyzing the array slides were carried out using GenePix 4000 series scanner and GenePix Pro/sup TM/ analyzing program, respectively. The expression profiles of 109 genes out of 6000 genes on the chip were significantly modulated in hypothalamus by the immobilization stress. Energy metabolism-, lipid metabolism-, apoptosis- and signal transduction-related genes were transcriptionally activated whereas DNA repair-, protein biosynthesis-, and structure integrity-related genes were down-regulated in hypothalamus. The 58 genes were up-regulated by the mRNA expression folds of 1.5 to 7.9. and the 51 genes were down-regulated by 1.5 - 3.5 fold. The 20 genes among them were selected to confirm the expression profiles by RT-PCR. The mRNA expression levels of Tnfrsf1a (apoptosis), Calm2 (cell cycle), Bag3 (apoptosis), Hspe1 (protein folding), Aatk (apoptosis), Dffa (apoptosis), Itgb1 (cell adhesion), Vcam1 (cell adhesion), Fkbp5 (protein folding), BDNF (neuron survival) were restored to the normal one by the treatment of Boshimgeonbi-Tang.

• Journal of the Korean Institute of Intelligent Systems
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• v.18 no.4
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• pp.471-475
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• 2008

Microarray technology in biological science enables molecular level observations and analyses on the biological phenomina by allowing to measure the RNA expression profiles in cells. Microarray data analysis is applied in various purposes such as identifying significant genes which react to drug treatment, understanding the genome scale phenomina. In drug response experiments, the microarray-based gene expression analysis could provide meaningful information. It is sometimes needed to identify the genes which shows different expression behavior for treatment group and normal group each other. When the normal group shows the medium level expression, it is not easy to discriminate the group just by expression level comparison. This paper proposes a method which selects group-wise representative values for each gene and sets the value range of the groups in order to filter out the genes with specific pattern. It also shows some experiment results.

• Proceedings of the Korean Statistical Society Conference
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• 2002.05a
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• pp.175-181
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• 2002

cDNA microarray experiments permit us to investigate the expression levels of thousands of genes simultaneously and to make it easy to compare gene expression from different populations. However, researchers are asked to be cautious in interpreting the results because of the unexpected sources of variation such as systematic errors from the microarrayer and the difference of cDNA dye intensity. And the scanner itself calculates both of mean and median of the signal and background pixels, so it follows a selection which raw data will be used in analysis. In this paper, we compare the results in each case of using mean and median from the raw data and normalization methods in reducing the systematic errors with arm's skin cells of old and young males. Using median is preferable to mean because the distribution of the test statistic (t-statistic) from the median is more close to normal distribution than that from mean. Scaled print tip normalization is better than global or lowess normalization due to the distribution of the test-statistic.