• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.18
• /
• pp.8247-8252
• /
• 2016

Background: The ubiquitin-proteasome system (UPS) degrades a variety of proteins which attach to specific signals. The ubiquitination pathway facilitates degradation of damaged proteins and regulates growth and stress responses. This pathway is altered in various cancers, including acute lymphoblastic leukemia, head and neck squamous cell carcinoma and breast cancer. Recently it has been reported that expression of newly characterized human genes, UBE2Q1 and UBE2Q2, putative members of ubiquitin-conjugating enzyme family (E2), has been also changed in colorectal cancer. Epigenetics is one of the fastest-growing areas of science and nowadays has become a central issue in biological studies of diseases. According to the lack of information about the role of epigenetic changes on gene expression profiling of UBE2Q1 and UBE2Q2, and the presence of CpG islands in the promoter of these two human genes, we decided to evaluate the promoter methylation status of these genes as a first step. Materials and Methods: The promoter methylation status of UBE2Q1 and UBE2Q2 was studied by methylation-specific PCR (MSP) in tumor samples of 60 colorectal cancer patients compared to adjacent normal tissues and 20 non-malignant controls. The frequency of the methylation for each gene was analyzed by chi-square method. Results: MSP results revealed that UBE2Q2 gene promoter were more unmethylated, while a higher level of methylated allele was observed for UBE2Q1 in tumor tissues compared to the adjacent normal tissues and the non malignant controls. Conclusions: UBE2Q1 and UBE2Q2 genes show different methylation profiles in CRC cases.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.17
• /
• pp.7819-7824
• /
• 2015

Purpose: To subtype breast cancer (BC) in Saudi women according to the recent molecular classification and to correlate these subtypes with available clinicopathological parameters. Materials and Methods: Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (Her2/neu) immunostaining was semi-quantitatively assessed to define molecular subtypes of luminal A and B, HER-2 and triple negative (basal-like) in BC paraffin embedded sections from 115 Saudi female patients diagnosed between 2005 to 2015 at the Department of Pathology, King Fahd Hospital, Almadinah, Saudi Arabia. Results: The most common subtypes were luminal A (47%), followed by luminal B (27.8%) and basal like subtypes (18.3%), whereas HER-2 was the least common subtype (6.9%). Luminal A was predominantly found in the old age group, with low tumor grade (p<0.001) and small tumor size, whereas HER-2 and basal-like subtypes were significantly associated with young age, high tumor grade, lymph node metastasis and lymphovascular invasion (p<0.03, 0.004, 0.05 and 0.04 respectively). All subtypes showed advanced clinical stage at the time of presentation. Conclusions: Molecular subtypes of Saudi BC patients in Almadinah region are consistent with most of the worldwide subtyping. The biological behaviour of each molecular subtype could be expected based on its characteristic clinicopathological features. Along with other prognostic indicators, molecular subtyping would be helpful in predicting prognosis and management of our BC patients. We recommend screening and early diagnosis of BC in our population.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.8
• /
• pp.4157-4162
• /
• 2012

Background: Novel prognostic biomarkers or therapeutic molecular targets for laryngeal squamous cell carcinoma (LSCC) are an urgent priority. We here sought to identify multiple novel LSCC-associated genes. Methods: Using high-density microarray expression profiling, we identified multiple genes that were significantly altered between human LSCCs and paired normal tissues. Potential oncogenic functions of one such gene, DCUN1D5, were further characterized in vitro. Results: Our results demonstrated that DCUN1D5 was highly expressed in LSCCs. Overexpression of DCUN1D5 in vitro resulted in 2.7-fold increased cellular migration, 67.5% increased invasive capacity, and 2.6-fold increased proliferation. Endogenous DCUN1D5 expression was decreased in a time-dependent manner after genotoxic stress, and silencing of DCUN1D5 by siRNA decreased the number of cells in the S phase by 10.2% and increased apoptosis by 11.7%. Conclusion: Our data suggest that DCUN1D5 in vitro might have vital roles in DNA damage response, but further studies are warranted to assess its significance in vivo.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.4
• /
• pp.1675-1679
• /
• 2014

Objectives: MicroRNAs (miRNAs) are important regulators of many physiological and pathological processes, including tumorigenesis and metastasis. In this study, we sought to determine the underlying molecular mechanisms of metastatic cervical carcinoma by performing miRNA profiling. Methods: Tissue samples were collected from ten cervical squamous cancer patients who underwent hysterectomy and pelvic lymph node (PLN) dissection in our hospital, including four PLN-positive (metastatic) cases and six PLN-negative (non-metastatic) cases. A miRNA microarray platform with 1223 probes was used to determine the miRNA expression profiles of these two tissue types and case groups. MiRNAs having at least 4-fold differential expression between PLN-positive and PLN-negative cervical cancer tissues were bioinformatically analyzed for target gene prediction. MiRNAs with tumor-associated target genes were validated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Results: Thirty-nine miRNAs were differentially expressed (>4-fold) between the PLN-positive and PLN-negative groups, of which, 22 were up-regulated and 17 were down-regulated. Sixty-nine percent of the miRNAs (27/39) had tumor-associated target genes, and the expression levels of six of those (miR-126, miR-96, miR-144, miR-657, miR-490-5p, and miR-323-3p) were confirmed by quantitative (q)RT-PCR. Conclusions: Six MiRNAs with predicted tumor-associated target genes encoding proteins that are known to be involved in cell adhesion, cytoskeletal remodeling, cell proliferation, cell migration, and apoptosis were identified. These findings suggest that a panel of miRNAs may regulate multiple and various steps of the metastasis cascade by targeting metastasis-associated genes. Since these six miRNAs are predicted to target tumor-associated genes, it is likely that they contribute to the metastatic potential of cervical cancer and may aid in prognosis or molecular therapy.

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

• Journal of the Institute of Electronics Engineers of Korea SD
• /
• v.39 no.1
• /
• pp.1-11
• /
• 2002

In this paper, new simple method for the calculation of depletion region under complex geometry and general purpose numerical simulator that could handle this were developed and applied in the analysis of SCM with nanoscale tip, which is a promising tool for high resolution dopant profiling. Our simple depletion region seeking algorithm alternatively switches material of elements to align ionized element boundary with contour of zero potential. To prove the validity of our method we examined whether our results satisfy the definition of depletion region and compared those with known values of un junction and MOS structure. By modeling of capacitance based on the shape of depletion region and potential distribution, we could calculate the CV curve and dC/dV curve between silicon substrate and nanoscale SCM tip.

• Journal of Ginseng Research
• /
• v.40 no.2
• /
• pp.151-159
• /
• 2016

Background: Ginsenoside-Rg3, the pharmacologically active component of red ginseng, has been found to inhibit tumor growth, invasion, metastasis, and angiogenesis in various cancer models. Previously, we found that 20(R)-ginsenoside-Rg3 (Rg3) could inhibit angiogenesis. Since microRNAs (miRNAs) have been shown to affect many biological processes, they might play an important role in ginsenoside-mediated angiomodulation. Methods: In this study, we examined the underlying mechanisms of Rg3-induced angiosuppression through modulating the miRNA expression. In the miRNA-expression profiling analysis, six miRNAs and three miRNAs were found to be up- or down-regulated in vascular-endothelial-growth-factor-induced human-umbilical-vein endothelial cells (HUVECs) after Rg3 treatment, respectively. Results: A computational prediction suggested that mature hsa-miR-520h (miR-520h) targets ephrin receptor (Eph) B2 and EphB4, and hence, affecting angiogenesis. The up-regulation of miR-520h after Rg3 treatment was validated by quantitative real-time polymerase chain reaction, while the protein expressions of EphB2 and EphB4 were found to decrease, respectively. The mimics and inhibitors of miR- 520h were transfected into HUVECs and injected into zebra-fish embryos. The results showed that overexpression of miR-520h could significantly suppress the EphB2 and EphB4 protein expression, proliferation, and tubulogenesis of HUVECs, and the subintestinal-vessel formation of the zebra fish. Conclusion: These results might provide further information on the mechanism of Rg3-induced angiosuppression and the involvement of miRNAs in angiogenesis.

• Journal of Ginseng Research
• /
• v.42 no.1
• /
• pp.57-67
• /
• 2018

Background: Ginseng contains many small metabolites such as amino acids, fatty acids, carbohydrates, and ginsenosides. However, little is known about the relationships between microorganisms and metabolites during the entire ginseng fermentation process. We investigated metabolic changes during ginseng fermentation according to the inoculation of food-compatible microorganisms. Methods: Gas chromatography mass spectrometry (GC-MS) datasets coupled with the multivariate statistical method for the purpose of latent-information extraction and sample classification were used for the evaluation of ginseng fermentation. Four different starter cultures (Saccharomyces bayanus, Bacillus subtilis, Lactobacillus plantarum, and Leuconostoc mesenteroide) were used for the ginseng extract fermentation. Results: The principal component analysis score plot and heat map showed a clear separation between ginseng extracts fermented with S. bayanus and other strains. The highest levels of fructose, maltose, and galactose in the ginseng extracts were found in ginseng extracts fermented with B. subtilis. The levels of succinic acid and malic acid in the ginseng extract fermented with S. bayanus as well as the levels of lactic acid, malonic acid, and hydroxypruvic acid in the ginseng extract fermented with lactic acid bacteria (L. plantarum and L. mesenteroide) were the highest. In the results of taste features analysis using an electronic tongue, the ginseng extracts fermented with lactic acid bacteria were significantly distinguished from other groups by a high index of sour taste probably due to high lactic acid contents. Conclusion: These results suggest that a metabolomics approach based on GC-MS can be a useful tool to understand ginseng fermentation and evaluate the fermentative characteristics of starter cultures.

• The Journal of Internal Korean Medicine
• /
• v.34 no.2
• /
• pp.134-146
• /
• 2013

Objectives : Auklandia Lappa (ALE) is one of the herbs used frequently to treat abdominal pain and diarrhea and reported anti-inflammatory activity by suppressing proinflammatory cytokines. This study was designed to investigate whether ALE could show protective activities on experimental colitis induced by dextran sulfate sodium (DSS) models. Methods : Colitis was induced by DSS in Balb/c mice. ALE 10, 30, 100 and 300 mg/kg were orally administered twice a day for 7 days in DSS model. Mice weight was measured daily. Scoring of clinical findings was measured every other day. Colon length, edema, fecal blood and histological damages were assessed at day 7 in DSS model. In histological analysis, we checked cryptal glands, surface epithelium, submucosa, transmural, stroma and scored degree of inflammatory cell damage by modified histological scoring. We also calculated cytokines concentrations including IFN-${\gamma}$, TNF-${\alpha}$, IL-6, IL-$1{\beta}$, IL-17, IL-23, IL-10 and TGF-${\beta}1$ by Biometric Multiplex Cytokine Profiling method. Results : ALE showed the protective effects on DSS-induced experimental colitis. ALE inhibited shortening of colon length and histological damages of colon does-dependently, but it did not inhibit weight loss. ALE also inhibited IFN-${\gamma}$ and IL-6 expression, and upregulated cytokines (IL-10, TGF-${\beta}1$) related to regulatory T cell differentiation and proliferation. Conclusions : The current results demonstrate the clinical utility of ALE in traditional medicine and indicate the possibility of potent drug development of inflammatory bowel diseases from natural products. Further investigations for exact mechanisms will be needed.

• Journal of Gastric Cancer
• /
• v.2 no.4
• /
• pp.213-220
• /
• 2002

Purpose: The cDNA microarray provides a powerful alternative with an unprecedented view in monitoring geneexpression levels and leads to discoveries of regulatory pathways involved in complicated biological processes. Our aim is to explore the different gene-expression patterns in gastric adenocarcinomas. Materials and Methods: By using a cDNA microarray representing 4,600 cDNA clusters, we studied the expression profiling in 10 paired gastric adenocarcinoma samples and in adjacent noncancerous gastric tissues from the same patients. Alterations in the gene-expression levels were confirmed by Vsing Northern blots and reverse-transcription PCR (RT-PCR) in all of 4 randomly selected genes. Results: Genes those were expressed differently in cancer ous and noncancerous tissues were identified. 44 (of which 26 were known) and 92 (of which 43 were known) genes or cDNA were up- and down-regulated, respectively, in more than $80\%$ of the gastric adenocarcinoma samples. In cancer ous tissues, genes related to gene/protein expression, cellcycle regulation, and metabolism were mostly up-regulated whereas genes related to the oncogene/tumor suppressor gene, cell structure/motility, and immunology were mostly down-regulated. The semi-quantitative RT-PCR results for the four genes we tested were consistent with the array findings. Conclusions: These results provide not only a new molecular basis for understanding the biological properties of gastric adenocarcinomas but also a useful resource for future development of therapeutic targets and diagnostic markers for gastric adenocarcinomas.