• Journal of Life Science
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• v.17 no.7 s.87
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• pp.996-1001
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• 2007

To investigate whether sulindac, sulindac sulfone, and sulindac sulfide could affect cancer cell viabilities, human colorectal HCTl16 cells were treated with 10 ${\mu}M$ of each NSAID. Among treated NSAms, sulindac sulfide dramatically decreased the cell viabilities detected by MTS and the cytotoxic effect showed dose-dependent manner. To understand the molecular mechanism of cell death in response to sulindac sulfide treatment, we performed oligo DNA microarray analysis. We found that 23 genes were up-regulated more than 2 folds, whereas 33 genes were down-regulated more than 2 folds by treatment of 10 ${\mu}M$ sulindac sulfide. Among the up-regulated genes, we selected 3 genes (NAG-1, DDIT3, PCK2) and performed RT-PCR and quantitative real-time PCR to cofirm microarray data. The results of RT-PCR and real-time PCR were highly accorded with those of microarray experiment. As NAG-1 is well-known gene as tumor suppressor, we detected changes of NAG-1 expression by 10 ${\mu}M$ of sulindac, sulindac sulfone, and sulindac sulfide. The results of RT-PCR and quantitacve real-time PCR indicated that sulindac sulfide was the strongest inducer of NAG-1 among treated NSAIDS. This result implies that induction of NAG-1 by sulindac sulfide plays important role in cell death of colorectal cancer. Overall, we speculate that these results may be helpful in understanding the molecular mechanism of the cancer chemoprevention by sulindac sulfide in human colorectal cancer.

• Genomics & Informatics
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• v.4 no.1
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• pp.23-32
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• 2006

In order to investigate the molecular basis of the aging process in brain, we have employed high-density oligonucleotide microarrays providing data on 10,108 gene clusters to define transcriptional patterns in three brain regions, cerebral cortex, cerebellum, and hippocampus. Comparison of the expression patterns between young (6-week-old) and aged (17-month-old) C57BL/6 male micerevealed that about ten percent (1098) of the genes showed a significant change in the expression level in at least one of the three tissues. Among them, 23 genes were upregulated and 62 genes were downregulated in all three tissues of the old mice. The number of genes upregulated exclusively in hippocampus (337) was much larger compared to other tissues. Gene ontology-based analysis showed the genes related with signal transduction or molecular transports are more likely to be upregulated than downregulated in the aging process of hippocampus. These data may provide some useful means for elucidating the molecular aspect of aging in hippocampus and other regions in brain.

• The Korean Journal of Applied Statistics
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• v.25 no.2
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• pp.269-277
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• 2012

In microarray data analysis, recent efforts have focused on the discovery of gene sets from a pathway or functional categories such as Gene Ontology terms(GO terms) rather than on individual gene function for its direct interpretation of genome-wide expression data. We introduce a meta-analysis method that combines $p$-values for changes of each gene in the group. The method measures the significance of overall treatment-induced change in a gene group. An application of the method to a real data demonstrates that it has benefits over other statistical methods such as Fisher's exact test and permutation methods. The method is implemented in a SAS program and it is available on the author's homepage(http://cafe.daum.net/go.analysis).

• Clinical and Experimental Reproductive Medicine
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• v.39 no.2
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• pp.87-93
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• 2012

Objective: Lin28 has been known to control the proliferation and pluripotency of embryonic stem cells. The purpose of this study was to determine the downstream effectors of Lin28 in mouse embryonic stem cells (mESCs) by RNA interference and microarray analysis. Methods: The control siRNA and Lin28 siRNA (Dharmacon) were transfected into mESCs. Total RNA was prepared from each type of transfected mESC and subjected to reverse transcription-polymerase chain reaction (RT-PCR) analysis to confirm the downregulation of Lin28. The RNAs were labeled and hybridized with an Affymetrix Gene-Chip Mouse Genome 430 2.0 array. The data analysis was accomplished by GenPlex 3.0 software. The expression levels of selected genes were confirmed by quantitative real-time RT-PCR. Results: According to the statistical analysis of the cDNA microarray, a total of 500 genes were altered in Lin28-downregulated mESCs (up-regulated, 384; down-regulated, 116). After differentially expressed gene filtering, 31 genes were selected as candidate genes regulated by Lin28 downregulation. Among them, neuropeptide Y5 receptor and oocyte-specific homeobox 5 genes were significantly upregulated in Lin28-downregulated mESCs. We also showed that the families of neuropeptide Y receptor (Npyr) and oocyte-specific homeobox (Obox) genes were upregulated by downregulation of Lin28. Conclusion: Based on the results of this study, we suggest that Lin28 controls the characteristics of mESCs through the regulation of effectors such as the Npyr and Obox families.

• Genomics & Informatics
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• v.17 no.4
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• pp.45.1-45.3
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• 2019

To identify pathways associated with survival phenotypes using gene expression data, we recently proposed the hierarchical structural component model for pathway analysis of gene expression data (HisCoM-PAGE) method. The HisCoM-PAGE software can consider hierarchical structural relationships between genes and pathways and analyze multiple pathways simultaneously. It can be applied to various types of gene expression data, such as microarray data or RNA sequencing data. We expect that the HisCoM-PAGE software will make our method more easily accessible to researchers who want to perform pathway analysis for survival times.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2375-2382
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• 2016

Cancer is a major health problem in Oman. It is reported that cancer incidence in Oman is the second highest after Saudi Arabia among Gulf Cooperation Council countries. Based on GLOBOCAN estimates, Oman is predicted to face an almost two-fold increase in cancer incidence in the period 2008-2020. However, cancer research in Oman is still in its infancy. This is due to the fact that medical institutions and infrastructure that play central roles in data collection and analysis are relatively new developments in Oman. We believe the country requires an organized plan and efforts to promote local cancer research. In this paper, we discuss current research progress in cancer diagnosis using machine learning techniques to optimize computer aided cancer detection and classification (CAD). We specifically discuss CAD using two major medical data, i.e., medical imaging and microarray gene expression profiling, because medical imaging like mammography, MRI, and PET have been widely used in Oman for assisting radiologists in early cancer diagnosis and microarray data have been proven to be a reliable source for differential diagnosis. We also discuss future cancer research directions and benefits to Oman economy for entering the cancer research and treatment business as it is a multi-billion dollar industry worldwide.

• Proceedings of the Korean Institute of Intelligent Systems Conference
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• 2007.04a
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• pp.417-420
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• 2007

마이크로어레이는 생명과학 분야에서 사용되는 대규모의 유전자 발현정도를 동시에 측정할 수 있는 도구이다. 마이크로어레이 실험은 많은 양의 데이터를 생성하기 때문에, 자동화된 효과적인 분석기법이 필요하다. 이 논문에서는 약물의 영향 분석을 위해 약물의 투여량 및 투여후의 시간대별로 샘플을 추출하여, 마이크로어레이를 이용하여 유전자의 발현량을 분석하는 경우에, 약물에 대해서 반응하는 유전자를 추출하는 데이터 마이닝 기법을 제안한다. 제안한 방법에서는 유전자의 발현정도값을 이전 시간의 값을 기준값으로 하여 증가, 감소, 답보에 해당하는 기호로 매핑하여, 분석자가 원하는 패턴을 보이는 유전자를 추천한다. 한편, 유전자의 상호간에 많은 영향을 주고 받기 때문에 특정 약물을 투여할 때, 이에 직접적인 영향을 받는 것도 있지만, 이와는 전혀 상관없이 동작하는 것도 있기 때문에, 제안한 방법에서는 이러한 약물 투여와 유의성이 있을 가능성이 있는 유전자만을 전처리과정을 통해서 필터링하는 기법을 활용한다. 제안한 방법은 실제 약물 투여 실험 샘플에 대한 마이크로어레이 데이터에 적용하여 활용가능성을 확인하였다.

• Journal of Periodontal and Implant Science
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• v.41 no.1
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• pp.30-43
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• 2011

Purpose: Under different culture conditions, periodontal ligament (PDL) stem cells are capable of differentiating into cementoblast-like cells, adipocytes, and collagen-forming cells. Several previous studies reported that because of the stem cells in the PDL, the PDL have a regenerative capacity which, when appropriately triggered, participates in restoring connective tissues and mineralized tissues. Therefore, this study analyzed the genes involved in mineralization during differentiation of human PDL (hPDL) cells, and searched for candidate genes possibly associated with the mineralization of hPDL cells. Methods: To analyze the gene expression pattern of hPDL cells during differentiation, the hPDL cells were cultured in two conditions, with or without osteogenic cocktails (${\beta}$-glycerophosphate, ascorbic acid and dexamethasone), and a DNA microarray analysis of the cells cultured on days 7 and 14 was performed. Reverse transcription-polymerase chain reaction was performed to validate the DNA microarray data. Results: The up-regulated genes on day 7 by hPDL cells cultured in osteogenic medium were thought to be associated with calcium/iron/metal ion binding or homeostasis (PDE1A, HFE and PCDH9) and cell viability (PCDH9), and the down-regulated genes were thought to be associated with proliferation (PHGDH and PSAT1). Also, the up-regulated genes on day 14 by hPDL cells cultured in osteogenic medium were thought to be associated with apoptosis, angiogenesis (ANGPTL4 and FOXO1A), and adipogenesis (ANGPTL4 and SEC14L2), and the down-regulated genes were thought to be associated with cell migration (SLC16A4). Conclusions: This study suggests that when appropriately triggered, the stem cells in the hPDL differentiate into osteoblasts/cementoblasts, and the genes related to calcium binding (PDE1A and PCDH9), which were strongly expressed at the stage of matrix maturation, may be associated with differentiation of the hPDL cells into osteoblasts/cementoblasts.

• Nutrition Research and Practice
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• v.1 no.1
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• pp.19-28
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• 2007

To identify regulatory molecules which play key roles in the development of obesity, we investigated the transcriptional profiles in 3T3-L1 cells at early stage of differentiation and analyzed the promoter sequences of differentially regulated genes. One hundred and sixty-one (161) genes were found to have significant changes in expression at the 2nd day following treatment with differentiation cocktail. Among them, 86 transcripts were up-regulated and 75 transcripts were down-regulated. The 161 transcripts were classified into 10 categories according to their functional roles; cytoskeleton, cell adhesion, immune, defense response, metabolism, protein modification, protein metabolism, regulation of transcription, signal transduction and transporter. To identify transcription factors likely involved in regulating these differentially expressed genes, we analyzed the promoter sequences of up- or - down regulated genes for the presence of transcription factor binding sites (TFBSs). Based on coincidence of regulatory sites, we have identified candidate transcription factors (TFs), which include those previously known to be involved in adipogenesis (CREB, OCT-1 and c-Myc). Among them, c-Myc was also identified by our microarray data. Our approach to take advantage of the resource of the human genome sequences and the results from our microarray experiments should be validated by further studies of promoter occupancy and TF perturbation.

• 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.