• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1015-1018
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• 2016

Background: Overexpression or amplification of human epidermal growth factor receptor-2 (HER2) is associated with grade of malignancy and a poor prognosis in breast cancer (BC). The aim of this study was to evaluate of value of HER2 as a prognostic marker, and to analyze associations with common histopathological parameters in BC cases. Materials and Methods: Between of 2007 to 2014, 260 patients with BC referred to Oncology Clinic provided cancer tissue samples which underwent immunohistochemistry (IHC) for markers. ER and PR positivity was defined as ${\geq}10%$ positive tumor cells with nuclear staining. HER2-positive was defined as either HER2 gene amplification by fluorescent in situ hybridization (FISH) or scored as 3+ by IHC. For HER2 (2+), FISH was performed to determine HER2 positivity. Results: The mean age at diagnosis for the patients with HER2-negative was significantly higher than in HER2-positive cases. Also, there were significant correlations between histological grade, nuclear grade, lymph node metastasis, tumor size, ER status, PR status, p53 overexpression and Ki-67 index with HER2 expression. HER2-negative lesions were of higher grade and more likely to be ER-negative, PR-negative, p53-positive, lymph node metastasis, with a tumor size<2cm and also $Ki-67{\geq}20%$ as compared to the HER2-positive group. Conclusions: Contrary to the results of other studies, HER2-positive tumors in our study had a lower Ki-67 index and were p53-positive. Also, Ki-67 proliferation index ${\geq}20%$ in more studies was associated with p53-positive.Therefore, tumors which are HER2-positive and have a Ki-$67{\geq}20%$ had a more aggressive behavior compared to HER2-positive and Ki-67<20% lesions.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6127-6130
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• 2013

This study aimed to investigate the association between p53 Arg72Pro polymorphism and the risk of human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) by conducting meta-analysis. The PubMed database was searched for relevant studies until May 30, 2013. Relevant studies were selected and data were extracted by two independent authors. Overall, subgroup, and sensitivity analyses were then conducted using the Comprehensive Meta-Analysis v2.2 software. Wild-genotype ArgArg was considered as reference [odds ratio (OR) = 1.00]. Nine studies involving 1071 HNSCC cases were obtained. Meta-analysis results indicated no association between p53 Arg72Pro polymorphism and the risk of HPV-related HNSCC: for Pro/Pro vs. Arg/Arg, OR = 1.17, 95% confidence interval (CI) = 0.70-1.98; for Arg/Pro vs. Arg/Arg, OR = 1.25, 95% CI = 0.97-1.72; and for (Pro/Pro + Arg/Pro) vs. Arg/Arg, OR = 1.28, 95% CI = 0.95-1.70. These meta-analysis results were supported by subgroup and sensitivity analysis results. In conclusions, p53 Arg72Pro polymorphism is a potential marker of HP infection-related HNSCC rather than a susceptibility gene polymorphism.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.3
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• pp.219-227
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• 2005

Purpose: Abnormalities in the p53 gene are regarded as the most consistent genetic abnormalities detected in head and neck squamous cell carcinogenesis. Two new members of the p53 gene family, p73 and p63 have recently been identified. They share considerable sequence homology with p53 in the transactivation, DNA binding, and oligomerization domains, indicating possible involvement in carcinogenesis. Disruption of the homeostatic balance between proliferation and apoptosis is widely believed to contribute to human oral carcinogenesis. The aim of this study was to analyze expression of p63 in squamous cell carcinogenesis and to compare with immunochemical markers representing cell proliferation and apoptosis. Materials and Methods: Using the Syrian hamster oral cancer model, the fraction of apoptotic (apoptotic index-AI), proliferating (mitotic index-MI) and p63 expressing keratinocytes were examined at normal, dysplastic and malignant oral epithelium using the TUNEL assay, PCNA and p63 immunostaining. Results: p63 significantly increased between normal and dysplastic epithelium and between dysplastic and malignant epithelium. PCNA significantly increased between normal and dysplastic epithelium and between normal and malignant epithelium. However, increase between dysplastic and malignant epithelium, though still increasing, was not statistically significant. The percentage of TUNEL positive cells increased from normal to dysplastic epithelium and returned to normal keratinocyte level in the malignant epithelium. However, differences between tissue types were not significant. The ratio of MI:AI increased significantly only in the dysplastic-malignant epithelial transition. The increase of p63 expression closely reflected the change in the MI:AI ratio during oral carcinogenesis. Conclusion: The p63 may be associated with the regulation of epithelial proliferation and apoptosis in DMBA-induced hamster buccal pouch squamous cell carcinogenesis. Further study is required to investigate which p63 isoforms are involved in hamster buccal pouch carcinogenesis.

• Microbiology and Biotechnology Letters
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• v.38 no.4
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• pp.442-447
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• 2010

We investigated anti-cancer and anti-proliferative activity of allicin and analyzed global gene expression changes by allicin treatment in human colorectal HCT116 cells. As a result, allicin decreased cell viabilities in a dose and time-dependent manner and induced apoptosis. Oligo DNA microarray analysis, we found that 7,840 genes were up-regulated more than 2-folds, whereas 10,010 genes were down-regulated more than 2-folds by $50\;{\mu}M$ allicin treatment. To confirm specific gene expressions, we performed RT-PCR. Consistent with the results of DNA microarray analysis, allicin dramatically induced ATF3 and NAG1 gene expression. Interestingly, NAG-1 protein expression was dependent on p53 presence. Taken together, our present results increase the knowledge of the molecular mechanism of anti-cancer and anti-proliferative activity mediated by allciin in human colorectal cancer cell.

• Journal of Animal Science and Technology
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• v.53 no.1
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• pp.15-22
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• 2011

The purpose of this study was to analyse of association between growth traits and single nucleotide polymorphisms (SNPs) polymorphism of phosphoglycerate kinase 2 (PGK 2) gene in pigs. The birth weight of piglet influences on weaning weight and survival rate that are import economic traits in pig industry. Also, these growth traits are representative factor to decrease a period getting to marketing weight as well as growth rate in pig. The PGK 2 is an isozyme that catalyzes the first ATP-generating step in the glycolytic pathwayand important enzyme related with energy metabolism. Twenty of SNPs were discoveredby genome structure analysis that compares the sequence on promoter and transcription region of PGK 2 gene in porcine chromosome 7. An association between PGK 2 SNPs and growth traits was analyzed in $F_2$ reciprocal-crossbred population between korean native pig (KNP) and Landrace. Association analysis indicated that polymorphism of the PGK 2 gene promoter region has significant effects on weight at birth (p<0.01) and weight at 3 weeks of age (p<0.0001). These results suggest that PGK 2 gene polymorphism was associated with energy metabolism and physiological function of growth in pig.

• Journal of Animal Science and Technology
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• v.53 no.1
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• pp.7-13
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• 2011

The aim of this study was to identify the polymorphism on exostosin-1 (EXT1) gene and to associate with economic traits in Hanwoo (Korean cattle). We sequenced for detection of single nucleotide polymorphism (SNP) with 24 unrelated individuals and identified four SNPs (T272196A, C272359T, G290964A and A302092G). Relationship between the genotypes of 583 Hanwoo individuals by PCR-RFLP and economic traits were analyzed by general linear model. In EXT1 gene, there were four SNPs associated with economic traits such as eye muscle area breeding value, marbling score breeding value, backfat and thickness breeding value (p<0.05 to p<0.01). In conclusion, this study indicates an important role of EXT1 gene in determining the meat quality or economic characteristics in Hanwoo.

• Radiation Oncology Journal
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• v.15 no.3
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• pp.187-195
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• 1997

Purpose : To analyze the involvement of apoptosis regulatory genes p53, $p21^{wart/cip1}$ bax and bcl-2 in induction of apoptosis by radiation in murine tumors. Materials and methods : The radiation-sensitive ovarian carcinoma OCa-1, and the radiation-resistant hepatocarcinorna HCa-I were used. Tumors, 8 mm in diameter, were irradiated with 25 Gy and at various times after irradiation, ranging from 1 to 48 h, were analyzed histologically for apoptosis and by western blot for alterations in the expression of these genes. The p53 status of the tumors were determined by the polymerase chain reaction-single strand conformation polymorphism assay. Results : Both tumors were positive for wild-type p53. Radiation inducesd apoptosis in OCa-1 but not in HCa-1. Apoptosis developed rapidly, peaked at 2 h after irradiation and returned to almost the background level at 48 h In OCa-1 radiation upregulated the expression of p53, $p21^{wart/cip1}$. and the bcl-2/bax ratio was decreased. In HCa-1 radiation increased the expression of both p53 and $p21^{wart/cip1}$, although the increase of the latter was small The bcl-2/bax ratio was greatly increased. In general the observed changes occurred within a few hours after irradiation, and either preceded or coincided with development of apoptosis Conclusions : The development of apoptosis required upregulation of both p53 and $p21^{wart/cip1}$ as well as a decrease in bcl-2/bax ratio. In contrast, an increase in bcl-2/bax ratio Prevented apoptosis in the presence of upregulated p53 and $p21^{wart/cip1}$ . These findings indentified the involvement of multiple oncogenes in apoptosis regulation in vivo and demonstrate the complexity that may be associated with the use of a single oncogene assessment for Predicting the outcome of cancer therapy with cytotoxic agents.

• BMB Reports
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• v.53 no.8
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• pp.425-430
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• 2020

Tumor necrosis factor-inducible gene 6 protein (TSG-6) is a cytokine secreted by mesenchymal stem cells (MSCs) and regulates MSC stemness. We previously reported that TSG-6 changes primary human hepatic stellate cells (pHSCs) into stem-like cells by activating yes-associated protein-1 (YAP-1). However, the molecular mechanism behind the reprogramming action of TSG-6 in pHSCs remains unknown. Cluster of differentiation 44 (CD44) is a transmembrane protein that has multiple functions depending on the ligand it is binding, and it is involved in various signaling pathways, including the Wnt/β-catenin pathway. Given that β-catenin influences stemness and acts downstream of CD44, we hypothesized that TSG-6 interacts with the CD44 receptor and stimulates β-catenin to activate YAP-1 during TSG-6-mediated transdifferentiation of HSCs. Immunoprecipitation assays showed the interaction of TSG-6 with CD44, and immunofluorescence staining analyses revealed the colocalization of TSG-6 and CD44 at the plasma membrane of TSG-6-treated pHSCs. In addition, TSG-6 treatment upregulated the inactive form of phosphorylated glycogen synthase kinase (GSK)-3β, which is a negative regulator of β-catenin, and promoted nuclear accumulation of active/nonphosphorylated β-catenin, eventually leading to the activation of YAP-1. However, CD44 suppression in pHSCs following CD44 siRNA treatment blocked the activation of β-catenin and YAP-1, which inhibited the transition of TSG-6-treated HSCs into stem-like cells. Therefore, these findings demonstrate that TSG-6 interacts with CD44 and activates β-catenin and YAP-1 during the conversion of TSG-6-treated pHSCs into stem-like cells, suggesting that this novel pathway is an effective therapeutic target for controlling liver disease.

• Korean Journal of Agricultural Science
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• v.22 no.2
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• pp.163-169
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• 1995

This study was carried out to examine the genetic constitution of serum proteins and enzymes in Holstein Friesian cattle population. The genetic variants of post-transferrin-2(pTf-2), transferrin(Tf), post-albumin(pAlb), ceruloplasmin(Cp) and amylase-I(Am-I) were analyzed by using PAGE(polyacrylamide gel electrophoresis) and STAGE(starch gel electrophoresis). In serum proteins, the pTf-2 locus were observed to be controlled by codominant alleles designated F and S, and the distribution of genotypes were 76.34, 14.50 and 9.10% for pTf-2 FF, FS and SS types, respectively. The gene frequencies of the pTf-2 F and S allele were 0.836 and 0.164. The Tf locus were found to be controlled by four alleles, Tf A, D1, D2 and E at a single locus, and the distribution of genotypes were 6.11, 32.06, 19.08, 1.53, 10.69, 18.32, 9.92 and 2.29% for Tf AA, AD1, AD2, AE, D1D1, D1D2, D2D2 and D2E type, respectively. The gene frequencies of the Tf A, D1, D2 and E wee 0.321, 0.359, 0.298 and 0.019. The pAlb locus were identified to be genetically controlled by two alleles, pAlb F and S allele, and the distribution of genotypes were 32.06, 29.77 and 38.17% for pAlb FF, FS and SS types, respectively. The gene frequencies of the pAlb F and S allele were 0.461 and 0.531. The Alb locus were observed to be controlled by Alb A and B allele, and the gene frequencies of these were 0.996 and 0.004. In serum enzymes, the Cp locus were found to be controlled by F and S allele, and the distribution of genotypes were 46.57, 27.48 and 25.95% for Cp FF, FS and SS types, respectively. The gene frequencies of F and S allele were 0.603 and 0.394. The Am-I locus were observed to be controlled by Am-I B and C allele, and the distribution of genotypes were 39.69, 21.73 and 38.93% for Am-I BB, BC and CC types, the gene frequencies of Am-I B and C were 0.503 and 0.497, respectively.

• Korean Journal of Pharmacognosy
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• v.40 no.2
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• pp.118-122
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• 2009

Methanol extracts of Orostachys japonicus A. Berger (OAB) were found to exhibit apoptosis induction of HL60 human acute promyelocytic leukemia cells. Treatment of OAB exerted strong cytotoxicity against HL60 cells. OAB induced DNA fragmentation of HL60 cells in a dose dependent manner. Nitric oxide production were also increased in OAB-treated RAW264.7 macrophage cell lines. Treatment of OAB increased the expression of p53 and iNOS gene and the expression of p53, $NF-{\kappa}B$ and iNOS protein in cultured HL60 and RAW264.7 cells. These results suggest that OAB are effective on strong anti-cancer properties and can be useful as a chemo-preventive agents.