• Proceedings of the Korean Society for Bioinformatics Conference
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• 2001.10a
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• pp.29-44
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• 2001

DNA damage by physical insult including UV and g-radiation might provoke genetic alterations in cells, which is followed by either acute cell death or tumorigenesis. The responsiveness to g-radiation depends on cellular context of target cells. To understand the mechanisms of checkpoint control, repair and cell death following genotoxic stimu]i, cDNA microarray can provide the gene expression profile. To make a profile of gene expression in irradiated Jurkat T cells, we hybridized the cDNA microarray using cDNA from g-irradiated Jurkat T cells. Jurkat T cells were exposed to 4Gy to 16Gy, and total RNA were extracted at 4 to 24 hrs after irradiation. The hybridization of the microarray to fluorescence-labeled cDNA from treated and untreated cells was analyzed by bioinformatic analysis to address relative changes in expression levels of the genes present in the array. Responses varied widely in different time points, suggesting acute stress response and chronic restoration or cell death. From these results we could select 384 genes related to radiation response in Tcells, and radiation response might be different in various types of cells. Using Radchip, we could separate "the exposed" from control PBMCs. We propose that Radchip might be useful to check the radiation research as well as radiation carcinogenesis.

• BMB Reports
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• v.42 no.5
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• pp.245-259
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• 2009

The process by which adult neural stem cells generate new and functionally integrated neurons in the adult mammalian brain has been intensely studied, but much more remains to be discovered. It is known that neural progenitors progress through distinct stages to become mature neurons, and this progression is tightly controlled by cell-cell interactions and signals in the neurogenic niche. However, less is known about the cell-intrinsic signaling required for proper progression through stages of adult neurogenesis. Techniques have recently been developed to manipulate genes specifically in adult neural stem cells and progenitors in vivo, such as the use of inducible transgenic mice and viral-mediated gene transduction. A critical mass of publications utilizing these techniques has been reached, making it timely to review which molecules are now known to play a cell-intrinsic role in regulating adult neurogenesis in vivo. By drawing attention to these isolated molecules (e.g. Notch), we hope to stimulate a broad effort to understand the complex and compelling cascades of intrinsic signaling molecules important to adult neurogenesis. Understanding this process opens the possibility of understanding brain functions subserved by neurogenesis, such as memory, and also of harnessing neural stem cells for repair of the diseased and injured brain.

• Molecules and Cells
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• v.20 no.3
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• pp.331-338
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• 2005

Ionizing radiation and doxorubicin both produce oxidative damage and double-strand breaks in DNA. Double-strand breaks and oxidative damage are highly toxic and cause cell cycle arrest, provoking DNA repair and apoptosis in cancer cell lines. To investigate the response of normal human cells to agents causing oxidative damage, we monitored alterations in gene expression in F65 normal human fibroblasts. Treatment with ${\gamma}$-irradiation and doxorubicin altered the expression of 23 and 68 known genes, respectively, with no genes in common. Both agents altered the expression of genes involved in cell cycle arrest, and arrested the treated cells in $G_2M$ phase 12 h after treatment. 24 h after ${\gamma}$-irradiation, the percentage of $G_1$ cells increased, whereas after doxorubicin treatment the percentage of $G_2M$ cells remained constant for 24 h. Our results suggest that F65 cells respond differently to ${\gamma}$-irradiation- and doxorubicin-induced DNA damage, probably using entirely different biochemical pathways.

• Tuberculosis and Respiratory Diseases
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• v.52 no.1
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• pp.5-13
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• 2002

Background: DNA repair plays a crucial role in protecting the genome from cancer-causing agents. Therefore, a reduced DNA repair capacity can increase the susceptibility to cancer. The human OGG1 (hOGG1) gene encodes DNA glycosylase/apurinic lyase and excise 8-hydroxyguanine, one of the major premutagenic DNA lesions, which is produced by oxygen radical forming agents including smoking. Recently several polymorphisms in the hOGG1 gene were identified, and it is possible that these polymorphism') may affect the DNA repair capacity and thus modulate cancer susceptibility. The relationship between the codon 326 polymorphism (Ser to Cys) in the hOGG1 gene and lung cancer risk was investigated. Materials and Method: The Ser326Cys genotypes were determined using PCR-RFLP analysis in 299 primary lung cancer patients and 186 healthy controls who were frequency (case:control=3:2) matched according to age and sex. Result: The frequencies of the Ser326Cys genotypes (Ser/Ser, Ser/Cys and Cys/Cys) among cases (23.4%, 51.8%, and 24.7%, respectively) were not significantly different from those among the controls (22.6%,52.1% and 25.3%, respectively). When the analyses were stratified according to age, sex, smoking status and packyears of smoking, no significant association between this polymorphism and lung cancer risk was found. Moreover, the Ser326Cys genotype showed no apparent relationship with any of the histological types of lung cancer. Conclusion: These result suggest that the hOGG1 Ser326Cys polymorphism is not a major contributor to individual lung cancer susceptibility in Koreans.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2917-2922
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• 2014

Background: The p53-binding protein 1 (TP53BP1) gene may be involved in the development of cancer through disrupting DNA repair. However, investigation of associations between TP53BP1 rs2602141 A/C polymorphism and cancer have yielded contradictory and inconclusive outcomes. We therefore performed a meta-analysis to evaluate the association between the TP53BP1 rs2602141 A/C polymorphism and cancer susceptibility. Materials and Methods: Published literature from PubMed, Medline, the Cochrane Library, EMbase, Web of Science, Google (scholar), CBMDisc, Chongqing VIP database, and CNKI database were retrieved. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed or random-effects models. Publication bias was estimated using funnel plots, Begg's and Egger's test. Results: A total of seven studies (3,018 cases and 5,548 controls) were included in the meta-analysis. Our results showed that the genotype distribution of TP53BP1 rs2602141 A/C was not associated with cancer risk overall. However, on subgroup analysis, we found that TP53BP1 rs2602141 A/C was associated with cancer risk within an allele model (A vs C, OR=1.14, 95%CI: 1.01-1.29) and a codominant model (AA vs CC, OR=1.36, 95%CI: 1.06-1.74) in Asians rather than in Caucasians. Subgroup analysis by cancer type, genotype, and with or without adjustment for controls showed no significant association. Conclusions: The findings suggested an association between rs2602141 A/C polymorphism in TP53BP1 gene and increased risk of cancer in Asians.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4153-4158
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• 2014

Background: This study was aimed to establish a novel method to simultaneously detect expression of four genes, ribonucleotide reductase subunit M1(RRM1), X-ray repair cross-complementing gene 1 (XRCC1), thymidylate synthase (TS) and class III ${\beta}$-tubulin (TUBB3), and to assess their application in the clinic for prediction of response of non-small cell lung cancer (NSCLC) to chemoradiotherapy. Materials and Methods: We have designed four gene molecular beacon (MB) probes for multiplex quantitative real-time polymerase chain reactions to examine RRM1, XRCC1, TUBB3 and TS mRNA expression in paraffin-embedded specimens from 50 patients with advanced or metastatic carcinomas. Twenty one NSCLC patients receiving cisplatin-based first-line treatment were analyzed. Results: These molecular beacon probes could specially bind to their target genes in homogeneous solutions. Patients with low RRM1 and XRCC1 mRNA levels were found to have apparently higher response rates to chemoradiotherapy compared with those with high levels of RRM1 and XRCC1 expression (p<0.05). The TS gene expression level was not significantly associated with chemotherapy response (p>0.05). Conclusions: A method of simultaneously detecting four molecular markers was successfully established and applied for evaluation of chemoradiotherapy response. It may be a useful tool in personalized cancer therapy.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.33 no.4
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• pp.308-313
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• 2011

Purpose: Beta-tricalcium phosphate (${\beta}$-TCP) is a synthetic calcium phosphate ceramic that has widely been used as a bone material to repair bone defects. Despite many clinical studies, the molecular mechanism whereby this biomaterial alters the gene expression in osteoblasts to promote bone formation is poorly understood. Thus, we attempted to address this question by using microarray techniques to identify the genes that are differentially regulated in osteoblasts exposed to ${\beta}$-TCP. Methods: By using DNA microarrays, we identified several genes whose expression levels were significantly up- or down-regulated in osteoblast-likeMG-63cells cultured with ${\beta}$-TCP at a concentration of 100 mg/10 ml for 24 hours. Results: The differentially expressed genes covered a broad range of functional activities: signal transduction, transcription, cell cycle regulation, vesicular transport, apoptosis, immunity, cytoskeletal elements and cell proliferation and differentiation. Conclusion: The gene expression changes related to cell proliferation and differentiation, vesicle transport, immunity and defense could affect the osteogenic activities of osteoblasts for bone regeneration. However, further studies will be required to verify the relative importance of these genes in bone formation, their temporal and spatial expression patterns and their interactions with each other.

• Molecular & Cellular Toxicology
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• v.1 no.2
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• pp.73-77
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• 2005

Nickel is the one of potent environmental, the occupational pollutants and the classified human carcinogens. It is a serious hazard to human health, when the metal exposure. To prevent human diseases from the heavy metals, it is seemingly important that understanding of how nickel exerts their toxicity and carcinogenic effect at a molecular and a genomic level. The process of nickel absorption has been demonstrated as phagocytosis, iron channel and diffusion. Uptaked nickel has been suggested to induce carcinogenesis via two pathways, a direct DNA damaging pathway and an indirect DNA damaging pathway. The former was originated from the ability of metal to generate Reactive Oxygen Species (ROS) and the reactive intermediates to interact with DNA directly. Ni-generated ROS or Nickel itself, interacts with DNAs and histones to cause DNA damage and chromosomal abnormality. The latter was originated from an indirect DNA damage via inhibition of DNA repair, or condensation and methylation of DNA. Cells have ability to protect from the genotoxic stresses by changing gene expression. Microarray analysis of the cells treated with nickel or nickel compounds, show the specific altered gene expression profile. For example, HIF-I (Hypoxia-Inducible Factor I) and p53 were well known as transcription factors, which are upregulated in response to stress and activated by both soluble and insoluble nickel compounds. The induction of these important transcription factors exert potent selective pressure and leading to cell transformation. Genes of metallothionein and family of heat shock proteins which have been known to play role in protection and damage control, were also induced by nickel treatment. These gene expressions may give us a clue to understand of the carcinogenesis mechanism of nickel. Further discussions on molecular and genomic, are need in order to understand the specific mechanism of nickel toxicity and carcinogenicity.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3047-3052
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• 2012

The enzyme encoded by the MGMT gene is involved in the repair of alkylated lesions formed in DNA by carcinogenic nitrosamines. Since dietary items consumed by the Kashmiri population contain high concentrations of these agents, it is biologically plausible that MGMT polymorphic variants may be associated with their risk of esophageal cancer. The present study was performed to assess whether non-synonymous SNPS at codon Leu84Phe and codon Ileu143Val of the MGMT gene, close to the active site of the protein, might be linked to predisposition of Kashmiris to esophageal cancer. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism on 92 cases and 77 healthy controls. Codon 84 and codon 143 SNPs of the MGMT gene were not associated with any increase in risk. While the frequency of the Phe allele at codon 84 in cases was (0.16), slightly higher than controls (0.12), the difference was not statistically significant. Similarly, the frequency of Valine allele in cases at codon 143 (0.08) and controls (0.09) was nearly equal. Moreover, no significant association of MGMT genotypes with the clinicopatholgic variables of esophageal cancer patients was observed. In conclusion, MGMT variants at codon 84 and codon143 may not be involved in the susceptibility of the Kashmiri population to esophageal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3667-3673
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• 2014

Background: colorectal cancer (CRC) is the third most common type of cancers and the fourth leading cause of death worldwide. In Saudi Arabia, CRC accounts for 8.5% of all tumors; it ranks first among all cancers in males and third among females. The aim of this study was to link between different PARP-1 mutations and risk of CRC in Saudi population and to determine common variants of PARP-1 in Saudi CRC patients and normal individuals. Materials and Methods: DNA samples were isolated from fifty CRC patients and from a comparable number of control subjects then sequenced to detect different variations present in exons 3, 17, and 21 of the PARP-1 gene. Results and Conclusions: When comparing the genotype and allele frequencies of all detected SNPs in CRC patients with those in controls, we found none were significantly different for all variants even the most common SNP in PARP-1 gene (Val762Ala). However, two novel alterations in exon 21 were found to be associated with increased risk of CRC. The variants identified as (1) Lys933Asn [p-value 0.0318] and (2) Lys945Asn [p-value 0.0257]. Our results suggest that PARP-1 Lys933Asn and Lys945Asn alterations could be associated with increased risk of CRC in the Saudi population.