• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.1
• /
• pp.355-358
• /
• 2013

XRCC1 genetic polymorphisms could be associated with increased risk of various cancer, including hepatocellular carcinoma (HCC), the fifth most common cancer. We here conducted a study to explore the role of selective SNPs of the XRCC1 and XPD genes in the prognosis of HCC. A total of 231 cases were collected, and genotyping of XRCC1 Arg194Trp, XRCC1 Arg399Gln, XPD Lys751Gln and XPD Asp312Asn was performed by duplex polymerase-chain-reaction with the confronting-two-pair primer method. Our findings indicated XRCC1 399Gln/Gln genotype was associated with a significant difference in the median survival time compared with patients carrying Arg/Trp and Arg/Arg genotypes, and individuals with XPD 751 Gln/ Gln genotype had a significantly greater survival time than patients carrying Lys/Lys and Lys/Gln genotypes. The Cox's regression analysis showed individuals carrying XRCC1 399Trp/Trp genotype had 0.55 fold risk of death from HCC than Arg/Arg genotype. Similarly, XPD 751Gln/Gln had a strong decreasein comparison to XPD Lys/Lys carriers with an HR of 0.34. These results suggest that polymorphisms in XRCC1 and XPD may have functional significance in the prognosis of HCC.

• Natural Product Sciences
• /
• v.19 no.1
• /
• pp.49-53
• /
• 2013

Paeonia lactiflora Pall (PL) has been used as a traditional herbal medicine in China, Korea, and Japan for more 1,200 years. PL has reported to have antioxidant activity and protective effect of cells from oxidative stress, although the mechanism has not been verified. FOXO3a is a transcription factor that binds to its target gene's consensus FOXO binding site. FOXO3a protein modulates the various biological functions including cell cycle control, apoptosis, DNA repair, and ROS detoxification. Therefore, FOXO3a activity is associated with cancer, aging, diabetes, infertility, neurodegeneration, and immune system dysfunction. Here we found that FOXO3a was activated by PL extract. Transcriptional target genes such as MnSOD, p27, and GADD45 were activated by PL extract. Protein levels of MnSOD and catalase were increased, consequently, ROS level was reduced in HEF cells by PL extract. These findings suggest that PL extract has an antioxidant activity through FOXO activation and thereby activation of FOXO target genes, MnSOD and catalase.

• The Journal of Natural Sciences
• /
• v.11 no.1
• /
• pp.45-54
• /
• 1999

In epistatic grouping of uvs genes in A. nidulans based on the sensitivities to 4-NQO, the same epistatic grouping was obtained as those for UV and MMS-sensitivities. Based on the MMS-sensitivities, uvsA demonstrated synergistic interactions to uvsF and uvsH, the UvsF group genes, but exhibited epistatic interactions to uvsB and uvsC. The same epistatic grouping was also seen for uvsI when UV was irradiated after 4h germination of conidia, showing synergistic interactions to uvsH, uvsC, and uvsB. However, epistatic interactions were observed with uvsF, which were different from those obtained in quiescent conidia by UV. Intergenic and intragenic recombination frequencies were normal in uvsI compared with wild type.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.4
• /
• pp.1725-1727
• /
• 2016

Breast cancer contributes to approximately 23% of the cancer cases identified and 14% of cancer related deaths worldwide. Including a strong association between genetic and environmental factors, breast cancer is a complex and multi factorial disorder. Two high penetration breast cancer susceptibility genes (BRCA1 and BRCA2) have been identified, and germ line mutations in these are thought to account for between 5% and 10% of all breast cancer cases. The human BRCA1 gene, located on 17q, is involved in the regulation of cell proliferation by aiding in DNA repair, transcriptional responses to DNA damage and cell cycle check points. Mutations in this gene enhance cell proliferation and facilitate formation of tumors. Two mutations, the 185 deletion of AG and the 4627 substitution from C to A, are founder mutations in the BRCA1 gene for breast cancer in Asian populations. Allele specific PCR was performed to detect these selected mutations in 120 samples. No mutation of 4627 C to A was detected in the samples and only one of the patients had the 185 del AG mutation in the heterozygous condition. Our collected samples had lower consanguinity and family history indicating the greater involvement of environmental as compared to genetic factors.

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

• BMB Reports
• /
• v.44 no.5
• /
• pp.317-322
• /
• 2011

Hereditary non-polyposis Colorectal Cancer (HNPCC) is an autosomal dominant inheritance syndrome. HNPCC is the most common hereditary variant of colorectal cancer (CRC), which accounts for 2-5% CRCs, mainly due to hMLH1 and hMSH2 mutations that impair DNA repair functions. Our study aimed to identify the patterns of hMSH2 and hMLH1 mutations in Chinese HNPCC patients. Ninety-eight unrelated families from China meeting Amsterdam or Bethesda criteria were included in our study. Germline mutations in MLH1 and MSH2 genes, located in the exons and the splice-site junctions, were screened in the 98 probands by direct sequencing. Eleven mutations were found in ten patients (11%), with six in MLH1 (54.5%) and five in MSH2 (45.5%) genes. One patient had mutations in both MLH1 and MSH2 genes. Three novel mutations in MLH1 gene (c.157_160delGAGG, c.2157dupT and c.-64G>T) were found for the first time, and one suspected hotspot in MSH2 (c.1168C>T) was revealed.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.17
• /
• pp.7413-7417
• /
• 2014

Background: Development of gastric cancer (GC) is a multistep process that requires alterations in the expression of oncogenes and tumor suppressor genes, occurring over several decades. The p53 tumor suppressor protein is involved in cell-cycle control, apoptosis and DNA repair. One of the most important regulators of p53 is MDM2, which acts as a negative regulator in the p53 pathway. Based on the key role of p53 and MDM2 in tumor suppression, polymorphisms that cause change in their function might affect cancer risk. We therefore elevated associations of the polymorphisms of p53 (R72P) and MDM2 (SNP309) with GC in Iran. Materials and Methods: A total of 104 patients with gastric cancer and 100 controls were recruited. Genomic DNA was extracted from fresh gastric samples. Genotyping of the p53 and MDM2 genes was performed using allele specific PCR (AS-PCR). Results: There was no significant difference between the p53 codon 72 polymorphism distribution in control and patient groups (p=0.54), but the G allele of MDM2 was found to be over-represented in patients (p=0. 01, Odds Ratio=2. 08, 95% Confidence Interval= 1.37-4.34). Conclusions: The p53 R72P seems not to be a potential risk factor for development of GC among Iranian patients, but our data suggest that MDM2 SNP309 might modify the risk related to GC.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.22 no.2
• /
• pp.60-78
• /
• 2009

Purpose: These experiments were undertaken to evaluate the effect of administration of Evodiae Fructus on ovarian functions and differential gene expressions related caspase-3, MAPK and MPG in female mice. Methods: We administered the Evodiae Fructus to 6-week-old female ICR mice for 4, 8, or 12 days. With different concentration of Evodiae Fructus, the female mice were injected PMSG and hCG for ovarian hyperstimulation. The mice divided into 3 groups for each experiment. We chose the caspase-3 for cell apoptosis, MAPK and MPG genes for cell viability and DNA repair. Results: In case of 4, 8, 12 day of Evodiae Fructus, we were examined the mean number of total ovulated oocytes and the number of morphologically normal oocytes. We were also examined the embryonic developmental competence in vitro. In addition we were also examined the differential expression of cell viability related genes, caspase-3, MAPK and MPG according to concentration and duration of Evodiae Fructus administration. MPG gene expressions for cell viability and DNA repaie were increased in dose dependent manner than that of control group in 4-day administration group. Conclusion: It is suggested that the medication of Evodiae Fructus has beneficial effect on reproductive functions of female mice via promotion of cell proliferation.

• Journal of Life Science
• /
• v.29 no.5
• /
• pp.514-523
• /
• 2019

We investigated the gene expression patterns and the mechanisms of action of the apoptotic response by microarray analysis of human keratinocyte HaCaT cells treated with ginsenoside Rb1, a saponin of Panax ginseng C. A. Meyer. Genes related to apoptosis, the G2/M transition of the mitotic cell cycle, cell division, mitotic nuclear division, and intracellular protein transport were 2-fold up-regulated in HaCaT cells treated with the ginsenoside Rb1, whereas genes related to DNA repair, regeneration fission, and extracellular matrix organization were 2-fold down-regulated. Apoptosis signaling may be mediated by FAS and PLA2G4A, and pathway analysis indicated that STAT3 might be an upstream regulator of these genes. The activity of FAS and PLA2G4A was verified by qPCR, which showed that FAS was increased about 2-fold in HaCaT cells treated with $10{\mu}g/ml$ of ginsenoside Rb1 for 24 hr, PLA2G4A was increased about twice after 6 hours, and gene expression was increased more than 2-fold after 24 hr. Knockdown of STAT3 with siRNA decreased FAS expression and increased PLA2G4A expression but only FAS was passed from the upstream regulator STAT3. These results indicate that STAT3, which is an upstream regulator, induces apoptosis via FAS during treatment with ginsenoside Rb1.

• Journal of Life Science
• /
• v.19 no.8
• /
• pp.1159-1163
• /
• 2009

It has been postulated that endoplasmic (ER) stress is involved in the development of several diseases. However, the detailed molecular mechanisms have not been fully understood. Therefore, we characterized a genetic network of genes induced by ER stress using cDNA microarray and gene set expression coherence analysis (GSECA), and identified gene function as well as several transcription regulators associated with ER stress. We analyzed time-dependent gene expression profiles in thapsigargin-treated Sk-Hep1 using an oligonucleotide expression chip, and then selected functional gene sets with significantly high expression coherence which was processed into functional clusters according to the expression similarities. The functions related to sugar binding, lysosome, ribosomal protein, ER lumen, and ER to golgi transport increased, whereas the functions with mRNA processing, DNA replication, DNA repair, cell cycle, electron transport chain and helicase activity decreased. Furthermore, functional clusters were investigated for the enrichment of regulatory motifs using GSECA, and several transcriptional regulators associated with regulation of ER-induced gene expression were found.