• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4393-4398
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• 2013

Background: Chromosomal translocations are genetic aberrations associated with specific non-Hodgkin lymphoma (NHL) subtypes. This study investigated the differential gene expression profile of Egyptian NHL cases based on a microarray approach. Materials and Methods: The study included tissue samples from 40 NHL patients and 20 normal lymph nodes used as controls. Total RNA was extracted and used for cDNA microarray assays. The quantitative real time polymerase chain reaction was used to identify the aberrantly expressed genes in cancer. Results: Significant associations of 8 up-regulated and 4 down-regulated genes with NHL were observed. Aberrant expression of a new group of genes not reported previously was apparent, including down-regulated NAG14 protein, 3 beta hydroxy-delta 5-c27 steroid oxi-reductase, oxi-glutarate dehydrogenase (lipo-amide), immunoglobulin lambda like polypeptide 3, protein kinase x linked, Hmt1, and caveolin 2 Tetra protein. The up-regulated genes were Rb binding protein 5, DKFZP586J1624 protein, protein kinase inhibitor gamma, zinc finger protein 3, choline ethanolamine phospho-transferase CEPT1, protein phosphatase, and histone deacetylase-3. Conclusions: This study revealed that new differentially expressed genes that may be markers for NHL patients and individuals who are at high risk for cancer development.

• Animal cells and systems
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• v.2 no.3
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• pp.403-410
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• 1998

The Tcf-1 (T cell specific factor-1) is a transcription factor uniquely expressed in T-lineage cells. Its expression is developmentally regulated, which is high in the specific stage of immature thymocytes, but is much lower in mature T cells. We cloned the Tcf-1 gene by subtractive hybridization and found it to be highly expressed in the thymus compared to the mRNA level in the spleen as expected. Since apoptosis occurs enormously in the thymus, we were interested in whether Tcf-1 gene expression could be regulated by such a high level of apoptotic assault. By using T cell hybridoma 70.7 cells, we induced apoptosis by incubating cells with anti-CD3 antibody in vitro. After apoptosis induction, Tcf-1 mRNA level was found to be significantly reduced compared to normal cells. Since Tcf-1 is a transcription factor for the CD3-e gene, we tested how CD3-e expression is regulated in apoptotic cells. The surface level of CD3-e protein is also down-regulated after apoptosis induction. Such a down-modulation of CD3-e protein would reduce the TCR/CD3 complex on the cell surface, which would be an important regulator for T cell apoptosis.

• Journal of Radiation Industry
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• v.6 no.3
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• pp.281-287
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• 2012

The model plant, Arabidopsis thaliana is the subject of an international genome research project. Massive doses of ionizing radiation have been shown to induce physiological changes in plants. The wild-type (Ler) Arabidopsis plants were irradiated with 100 Gy and 800 Gy of gamma-ray. Gibberellin (GA) affects developmental processes and responses according to the various environment conditions in diverse plant. The 13 GA isomers were analyzed at vegetative (VE) and reproductive (RE) stages by HPLC. Total GA contents were reduced with the increase in radiation doses at VE and RE stages. Specifically, levels of GA3, GA4, GA12, and GA34 were significantly reduced with the increase of radiation doses. Oligonucleotide microarrays analysis was performed with Arabidopsis plants at different developmental stages and doses of gamma-ray. Through the microarray data, we isolated 41 genes related to GA biosynthesis and signaling transduction. Expression of these genes was also decreased as the reduction of GA contents. Interestingly, in GA signaling related gene expression, gibberellin-responsive protein, putative (At2g18420) was down-regulated at VE and RE stages. Myb21 (At3g27810), Myb24 (At5g40350), and Myb57 (At3g01530) was down-regulated at RE stage. In GA biosynthesis related gene expression, YAP169 (At5g07200) and GA20ox2 (At5g51810) were down-regulated at 100 Gy treatment of VE stage and 800 Gy treatment of RE stage in cytoplasm, respectively. However, exceptively, GA3ox2 (At1g80340) was up-regulated at 100 Gy treatment of RE stage in cytoplasm. In this study, the wild type (Ler) Arabidopsis plants showed differences in response with development stage at the various doses of gamma-rays. GA contents change was reported in gamma irradiated plant.

• Molecular & Cellular Toxicology
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• v.2 no.3
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• pp.193-201
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• 2006

Cephalexin, one of most widely prescribed cephalosporin, has been reported to cause acute renal failure as a side effect in human and experimental animals. Although numerous animal studies have been reported for the cephalosporin nephrotoxicity, the molecular and cellular nephrotoxic mechanisms of cephalexin are still unknown. This investigation evaluated the time-dependent gene expression profile of kidney in mouse during cephalexin induced nephrotoxicity. C57BL/6 female mice were administered either saline or 1,000 mg/kg cephalexin intraperitoneally. Mice were sacrificed at 3, 6, and 24 hr after administration. Blood biochemical and histopathological results indicated cephalexin induced nephrotoxicity. Microarray experiment carried out using Affymetrix $GeneChip^{(R)}$. There were 198 informative genes that were significantly expressed >5-fold versus control at 3, 6, and 24 hr (p<0.01), of which 156 and 42 were up-and down-regulated, respectively. Major classes of up-regulated genes at 3, 6 hr included those involved in MAPK/Jak-STAT signaling pathway and immune response such as cytokine-cytokine receptor interaction and complement and coagulation cascades. At 24 hr, up-regulated genes were mainly involved in regeneration/repair and immune response; down-regulated genes were generally associated with transporters and intermediary metabolism. Among the up-regulated genes at 24 hr, several potential biomarkers on nephrotoxicity such as Kim-1, Fga, Timp1, and Slc34a2 were clustered in a same category. In addition, Tnfrsf12a and Lcn2 which were consistently up-regulated (>5 fold) were also included as potential biomarkers. These results may provide clues for elucidating the mechanism of cephalexin induced nephrotoxicity and evaluating potential biomarkers to assess nephrotoxicity.

• Proceedings of the Korean Society of Crop Science Conference
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• 2022.10a
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• pp.229-229
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• 2022

Rapeseed is a crop that is waterlogging sensitive, and it is necessary to breed waterlogging tolerance varieties. Our study presents the comparative transcriptome changes in two rapeseed lines, i.e., waterlogging-tolerant (tJ8634-B-30,) and - sensitive ('EMS26') lines under control and waterlogging stress treatments at the flowering stage. RNA-sequencing analysis revealed 13,279 differentially expressed genes (DEGs) for 'J8634-B-30' and 8,682 DEGs for 'EMS26' under waterlogging stress condition compared to control. Among DEGs of 'J8634-B-30', 6,818 were up-regulated and 6,461 were down-regulated. On the other hand, among the DEGs of 'EMS26', the number of down-regulated genes (5,240) were higher than that of up-regulated genes (3,442). Gene ontology enrichment analysis showed that DEGs related to glucan metabolic, cell wall, and oxidoreductase activity were significantly changed in 'J8634-B-30'. Kyoto Encyclopedia of Genes and Genomes (KEGG)-based analysis in 'J8634-B-30' identified up-regulated DEGs being involved in MAPK signaling pathways. In addition, the DEGs belonging to mechanisms responding to waterlogging stress, i.e., plant hormones, carbon metabolism, Reactive oxygen species (ROS), Nitric oxide (NO) etc. were compared in rapeseed lines. Several DEGs including ethylene-responsive transcription factor (ERF), constitutive triple response (CTR) (in ethylene signaling pathway), monodehydroascorbate Reductase (MDAR), NADPH oxidase (in ROS pathway), cytochrome c oxidase assembly protein (COX) (in NO pathway) up-regulated in 'J8634-B-30'. These outcomes provided the valuable information for further exploring the genetic mechanism of waterlogging tolerance in rapeseed.

• Archives of Pharmacal Research
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• v.27 no.4
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• pp.442-448
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• 2004

Wogonin (5,7-dihydroxy-8-methoxyflavone) is a down-regulator of cyclooxygenase-2 and inducible nitric oxide synthase expression, contributing to anti-inflammatory activity in vivo. For further characterization of modulatory activity on ploinflammatory gene expression in vivo, the effect of wogonin was examined in this experiment using animal models of skin inflammation. By topical application, wogonin inhibited an edematic response as well as ploinflammatory gene expression against contact dermatitis In mice. Wogonin inhibited ear edema ($19.4-22.6\%$) at doses of $50-200\;{\mu}g$/ear and down-regulated interleukin-$1{\beta}$ induction ($23.1\%$) at $200{\mu}g$/ear in phenol-induced simple irritation. Wogonin ($2{\times}50-2{\times}200{\mu}g$/ear) also inhibited edematic response ($51.2-43.9\%$) and down-regulated ploinflammatory gene expression of cyclooxygenase-2, interleukin-$1{\beta}$, interferon-$\gamma$, intercellular adhesion molecule-1 and inducible nitric oxide synthase with some different sensitivity against picryl chloride-induced delayed hypersensitivity reaction. All these results clearly demonstrate that wogonin is a down-regulator of ploinflammatory gene expression in animal models of skin inflammation. Therefore, wogonin may have potential for a new anti-inflammatory agent against skin inflammation.

• Archives of Pharmacal Research
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• v.18 no.5
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• pp.301-307
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• 1995

In the particulate fraction obtained from PKC-down regulated K562 cells by treatment for 24 h with 200nM TPA, phosphorylation of two proteins with molecular weight, 100 kDa and 23 kDa (designated p100 and p23, respectvely) was depleted and addition of exogenous purified PKC to this fraction failed to testore their phosphorylation. However, in the soluble fraction, all of phosphoproteins abolished by long-term treatment with TPA were restored by exogenously added PKC. Phosphorylation of two proteins was increased by short-term tretment (20 min), and diminished with the persistant exposure to TPA as well as at a concentration as low as 1nM. When K562 cells were treated with 1 nM and 200 nM TPA for 24 h, phosphorylation of p100 was restored with or without exogenous PKC on 2-3day and 6day after removal of treated TPA, respectively. Two-dimensional electrophoresis of phosphoproteins revealed that phosphorylated p100 (pl=5.9) and p66 species were completely absent from the particulate fraction of K562 cells treated with 200nM TPA for 24 h. These results suggest that the interaction of sensitive endogenous substrates, p100 and p23 with the plasma membrane might be regulated by PKC-down regulation without displacement to the cytosol and the interaction of p100 with the membrane might be reveersible.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4003-4007
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• 2016

Long interspersed elements-1s (LINE-1s) are dispersed all over the human genome. There is evidence that hypomethylation of LINE-1s and levels of sex steroids regulate gene expression leading to cancer development. Here, we compared mRNA levels of genes containing an intragenic LINE-1 in breast cancer cells treated with various sex steroids from Gene Expression Omnibus (GEO), with the gene expression database using chi-square analysis (http://www.ncbi.nlm.nih.gov/geo). We evaluated whether sex steroids influence expression of genes containing an intragenic LINE-1. Three sex steroids at various concentrations, 1 and 10 nM estradiol (E2), 10 nM progesterone (PG) and 10 nM androgen (AN), were assessed. In breast cancer cells treated with 1 or 10 nM E2, a significant percentage of genes containing an intragenic LINE-1 were down-regulated. A highly significant percentage of E2-regulated genes containing an intragenic LINE-1 was down-regulated in cells treated with 1 nM E2 for 3 hours (p<3.70E-25; OR=1.91; 95% CI=2.16-1.69). Similarly, high percentages of PG or AN-regulated genes containing an intragenic LINE-1 wwere also down-regulated in cells treated with 10 nM PG or 10 nM AN for 16 hr (p=9.53E-06; OR=1.65; 95% CI=2.06-1.32 and p=3.81E-14; OR=2.01; 95% CI=2.42-1.67). Interestingly, a significant percentage of AN-regulated genes containing an intragenic LINE-1 was up-regulated in cells treated with 10 nM AN for 16 hr (p=4.03E-02; OR=1.40; 95% CI=1.95-1.01). These findings suggest that intragenic LINE-1s may play roles in sex steroid mediated gene expression in breast cancer cells, which could have significant implications for the development and progression of sex steroid-dependent cancers.

• Journal of Life Science
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• v.27 no.3
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• pp.267-274
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• 2017

The patient with end-stage renal disease show several nervous complications. The factors contributing to the nervous complications are still incompletely characterized. Cyanate, known as one of the uremic toxins, is derived spontaneously from urea. To investigate the mechanism of cyanate-induced effect on C6 glioma cells, the glioma cells were treated with 0, 1, 5, 10, 20 and 40 mM cyanate. There was a dose-dependent decrease in cell viability and the decreased number of cell was observed in glioma cells by treatment with cyanate. Western blot showed the down- regulation of procaspase-3, which means up-regulation of caspase-3, and the up-regulation of caspase-8, but the down-regulation by cyanate. In addition, cDNA microarray showed 934 down-regulated genes and 165 up-regulated genes on 1,099 genes in cyanate treated group. Treatment with cyanate led to 16 down-regulated genes and 6 up-regulated genes on apoptosis category, and especially heat shock 70 kD protein 1A gene on the category of apoptosis was significantly up-regulated. These results suggest that cyanate can induce apoptosis through caspase-8 and caspase-3 in glioma cells and decrease of gene expression including apoptosis category in glioma cells. These effects of cyanate may play a role in the nervous complications of patient with end-stage renal disease.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8893-8900
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• 2014

Dysregulated expression of microRNAs (miRNAs) has been shown to be closely associated with tumor development, progression, and carcinogenesis. However, their clinical implications for gastric cancer remain elusive. To investigate the hypothesis that genome-wide alternations of miRNAs differentiate gastric cancer tissues from those matched adjacent non-tumor tissues (ANTTs), miRNA arrays were employed to examine miRNA expression profiles for the 5-pair discovery stage, and the quantitative real-time polymerase chain reaction (qRTPCR) was applied to validate candidate miRNAs for 48-pair validation stage. Furthermore, the relationship between altered miRNA and clinicopathological features and prognosis of gastric cancer was explored. Among a total of 1,146 miRNAs analyzed, 16 miRNAs were found to be significantly different expressed in tissues from gastric cancer compared to ANTTs (p<0.05). qRT-PCR further confirmed the variation in expression of miR-193b and miR-196a in the validation stage. Down-expression of miR-193b was significantly correlated with Lauren type, differentiation, UICC stage, invasion, and metastasis of gastric cancer (p<0.05), while over-expression of miR-196a was significantly associated with poor differentiation (p=0.022). Moreover, binary logistic regression analysis demonstrated that the UICC stage was a significant risk factor for down-expression of miR-193b (adjusted OR=8.69; 95%CI=1.06-56.91; p=0.043). Additionally, Kaplan-Meier survival curves indicated that patients with a high fold-change of down-regulated miR-193b had a significantly shorter survival time (n=19; median survival=29 months) compared to patients with a low fold-change of down-regulated miR-193b (n=29; median survival=54 months) (p=0.001). Overall survival time of patients with a low fold-change of up-regulated miR-196a (n=27; median survival=52 months) was significantly longer than that of patients with a high fold-change of up-regulated miR-196a (n=21; median survival=46 months) (p=0.003). Hence, miR-193b and miR-196a may be applied as novel and promising prognostic markers in gastric cancer.