• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6721-6726
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• 2013

Background: Changes in DNA methylation patterns are believed to be early events in hepatocarcinogenesis. A better understanding of methylation states and how they correlate with disease progression will aid in finding potential strategies for early detection of HCC. The aim of our study was to analyze the methylation frequency of tumor suppressor genes, P14, P15, and P73, and a mismatch repair gene (O6MGMT) in HCV related chronic liver disease and HCC to identify candidate epigenetic biomarkers for HCC prediction. Materials and Methods: 516 Egyptian patients with HCV-related liver disease were recruited from Kasr Alaini multidisciplinary HCC clinic from April 2010 to January 2012. Subjects were divided into 4 different clinically defined groups - HCC group (n=208), liver cirrhosis group (n=108), chronic hepatitis C group (n=100), and control group (n=100) - to analyze the methylation status of the target genes in patient plasma using EpiTect Methyl qPCR Array technology. Methylation was considered to be hypermethylated if >10% and/or intermediately methylated if >60%. Results: In our series, a significant difference in the hypermethylation status of all studied genes was noted within the different stages of chronic liver disease and ultimately HCC. Hypermethylation of the P14 gene was detected in 100/208 (48.1%), 52/108 (48.1%), 16/100 (16%) and 8/100 (8%) among HCC, liver cirrhosis, chronic hepatitis and control groups, respectively, with a statistically significant difference between the studied groups (p-value 0.008). We also detected P15 hypermethylation in 92/208 (44.2%), 36/108 (33.3%), 20/100 (20%) and 4/100 (4%), respectively (p-value 0.006). In addition, hypermethylation of P73 was detected in 136/208 (65.4%), 72/108 (66.7%), 32/100 (32%) and 4/100 (4%) (p-value <0.001). Also, we detected O6MGMT hypermethylation in 84/208 (40.4%), 60/108 (55.3%), 20/100 (20%) and 4/100 (4%), respectively (p value <0.001. Conclusions: The epigenetic changes observed in this study indicate that HCC tumors exhibit specific DNA methylation signatures with potential clinical applications in diagnosis and prognosis. In addition, methylation frequency could be used to monitor whether a patient with chronic hepatitis C is likely to progress to liver cirrhosis or even HCC. We can conclude that methylation processes are not just early events in hepatocarcinogenesis but accumulate with progression to cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3395-3402
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• 2015

Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. Materials and Methods: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. Results: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5033-5036
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• 2012

Objective: To study the relationship between expression of $p57^{KIP2}$ and prognosis and other clinicopathological parameters in invasive breast cancers. Methods: We assessed the expression of $p57^{KIP2}$ in 89 cases of invasive breast cancer and 20 cases of normal breast tissue by immunohistochemical methods and analyzed the results with SPSS software (ver. 16.0). Result: The positive expression rates of $p57^{KIP2}$ protein in the invasive breast cancers and surrounding normal tissue were 30.3% (27/89) and 65% (13/20), respectively. Cases with no $p57^{KIP2}$ expression exhibited a significantly higher post-operative distant metastasis rate than those with $p57^{KIP2}$ expression (37.9% vs. 14.8%; P = 0.01). DFS analysis showed that $p57^{KIP2}$-/C-erbB-2+ tumors also exhibited a significantly higher post-operative distant metastasis rate than the other groups (66.7% vs. 29.2%; P = 0.007), as did $p57^{KIP2}$-/p53+ tumors (64.3% vs. 22.7%; P = 0.001). Survival analysis revealed that $p57^{KIP2}$ was associated with breast cancer-specific survival overall (P = 0.045, log-rank test). Subgroup analysis demonstrated that individuals with $p57^{KIP2}$-/C-erbB-2+tumors experienced significantly worse post-operative survival than those with $p57^{KIP2}$-/C-erbB-2- or other tumors (P = 0.006, log-rank test). $p57^{KIP2}$-/p53+ tumors were associated with significantly worse post-operative survival than $p57^{KIP2}$-/p53- or other tumors (P = 0.001, log-rank test). Cox regression analysis showed that $p57^{KIP2}$ was a non-independent prognostic factor for breast cancer (P = 0.303). Conclusions: $p57^{KIP2}$ is expressed at low levels in invasive breast cancer and is associated with better overall survival rate and disease-free survival in breast cancer patients, but it was a non-independent prognostic factor for breast cancer. Thus, the connection between $p57^{KIP2}$/p53 and $p57^{KIP2}$/C-erbB-2 may provide biomarkers for breast cancer.

• Journal of the East Asian Society of Dietary Life
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• v.18 no.6
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• pp.918-926
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• 2008

It is well known non-drug therapy for hypertension patients can reduce blood pressure. These types of therapy include maintaining ones ideal body weight, quitting smoking, consuming large amounts of fruits and vegetables consuming low levels of saturated fat and salt and regular exercise. Fermented milk protein derived biologically active peptides such as isoleucine-proline-proline_(IPP) or valine-proline-proline_(VPP) have been shown to lower blood pressure in hypertensive subjects. This study was conducted to investigate the antihypertensive effects of medical nutritional therapy _(MNT) in accordance with the consumption of fermented milk enriched with IPP and VPP. To accomplish this, we conducted a randomized case-controlled study of 43 subjects who had blood pressure levels greater than 120/80 mmHg. The subjects in the study group were randomly allocated into two groups, an MNT + fermented milk (100mL/day) group (n=21) and an MNT+L. helveticus fermented milk with tripeptides (IPP=2.2mg, VPP=2.6mg/100mL) group (n=22). The MNT included weight management, reduction of sodium, total fat and saturated fat intake, increased intake of fruits and vegetables, and increased intake of low fat dairy products. The treatments were administered for 12 weeks during which time no drug interventions were conducted. The daily intakes of total calories, fats, cholesterol and Na decreased significantly after 12 weeks of MNT in the control and the experimental groups. In addition, the systolic blood pressure de creased significantly in the control and experimental groups; however, the diastolic blood pressure only decreased significantly in the experimental group. Overall, the results of this study indicate that the intake of fermented milk containing IPP and VPP in conjunction with MNT exerted positive effects on the blood pressure of pre- and hypertensive subjects.

• Archives of Craniofacial Surgery
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• v.10 no.2
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• pp.67-70
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• 2009

Purpose: Anatomical basis around orbit can be helpful in periorbital surgery, and there are many articles about measurement between periorbital reference points. In 1967, Jones and Evans measured the orbital wall thickness of Asian cadavers and this article has been cited more than 50 times. But there is no research in orbital thickness in Vivo. Author's idea was based on difference between live human and human cadaver. Material & Method: We conducted this study from 63 consecutive blow out fracture patients between January, 2000 to june, 2005 by collecting the bone fragments and measured the thickness of that fragment using vernia calipers. Anatomically, orbital floor is separated two area by inferior orbital fissure and we measured each area. Three areas were zone I (medial wall), zone II (medial to inferior orbital fissure) and zone III (lateral to inferior orbital fissure). Result: When the overall results were considered, the thickness of Zone I (medial wall of orbit) was average $0.131{\pm}0.006mm$ in male and $0.129{\pm}0.007mm$ in female and Zone II (medial side of orbital floor) was $0.251{\pm}0.005mm$ in male and $0.245{\pm}0.006mm$ in female, Zone III (lateral side of orbital floor) was $0.237{\pm}0.006mm$ in male and $0.226{\pm}0.006mm$ in female. There were no statistical difference between orbital wall thickness of male and female. Also, orbital wall thickness of adults measured $0.130{\pm}0.005mm$, $0.250{\pm}0.005mm$, $0.232{\pm}0.006mm$ in Zone I, Zone II, Zone III and $0.128{\pm}0.006mm$, $0.233{\pm}0.005mm$, $0.215{\pm}0.007mm$ in Zone I, Zone II, Zone III from childs, and there were no statistical difference between adult and child. Conclusion: This article is the first study about Korean orbital wall thickness, and can be helpful to periocular surgery.

• IMMUNE NETWORK
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• v.2 no.2
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• pp.86-90
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• 2002

Background: Host genetic polymorphisms in the HIV-1 co-receptor CCR5 and CCR2b and SDF-1, ligand for co-receptor CXCR4, have been known to be associated with the resistance of HIV infection and/or the delayed disease progression in HIV-infected patients. Methods: We examined the frequencies of SDF1-3'A and CCR2b-64I alleles of 354 Koreans including 100 HIV-uninfected persons, 13 discordant spouses of HIV-infected persons, and 241 HIV-infected persons. The genotyping assays of SDF1 and CCR2b genes were carried out by polymerase chain reaction-restriction fragment length polymorphism. Results: The frequencies of CCR2b-64I and SDF1-3'A alleles in Koreans were very high compared with Caucasians and blacks. Observed frequencies of CCR2b-64I and SDF1-3'A allelic variants were 25.1% and 28.7%, respectively. The frequency of the CCR2b-64I allele in Koreans was 2~4 times higher than those of other ethnic groups with the exception of Asian. The frequencies of CCR2b-64I and SDF1-3'A genotypes did not show the significant difference between HIV-infected and uninfected Koreans. However, the prevalence of CCR2b-64I genotype of the LTNP group was about two times higher than that of the remainder group (P< 0.05). Four (45%) out of 9 LTNPs (long-term nonprogressors) showed having the SDF1-3'A allele and 7 (78%) out of 9 LTNPs carried the CCR2b-64I allele. 3 (33%) out of 9 LTNPs had both SDF1-3'A and CCR2b-64I alleles. But none of 5 RPs (rapid progressors) appeared to have both SDF1-3'A and CCR2b-64I alleles. Conclusion: The different genetic backgrounds in study populations may affect the disease progression and the AIDS epidemic in each country. Further studies need to define whether high frequencies of CCR2b-64I and SDF1-3'A allelic variants may affect the HIV disease progression.

• Journal of Preventive Medicine and Public Health
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• v.32 no.3
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• pp.306-316
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• 1999

Objectives: In Korea, as in most countries, there will be a sharp increase in the number of dementia patients in the near future. However basic data on dementia prevalence, which is important in defining epidemiologic characteristics and in implementing preventive strategy, are limited. This study was conducted to estimate the prevalence rate of dementia in the urban elderly aged 65 or older in Kwangmyung, Korea. Methods: A two phase design was used for case finding and case identification. In phase I, a representative sample aged 65 or older was selected and interviewed by door-to-door survey with a Korean version of the Mini-Mental State Examination (K-MMSE). In phase II, Of the 946 subjects interviewed in phase 1,356 elderly were randomly selected disproportionately according to K-MMSE score. Of these elderly, 223 (61.5%) underwent standardized clinical evaluations, including psychiatric interview, neurological examination, and neuropsychological assessment. Dementia was diagnosed by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. The diagnosis of Alzheimer's disease (AD) was made by National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and feinted Disorders Association(NINCDS-ADRDA) criteria and vascular dementia (VD) by DSM-IV. Results: The overall weighted prevalence rate of all dementia among Kwangmyung residents aged 65 or older was 12,8%(age-adjusted rate: 13,0%, 95% Confidence Interval[CI]: 10.6-15.3%). Women had much higher prevalence rate than men even when age was controlled(15.9%[95% CI 12.6-19.2%] vs 7.5%[95% CI 4.0-10.4%]), The rates of dementia were 5.2%, 12.2%, 17.0%, and 34.3% for the age groups of 65-69, 70-74, 75-79 and 80 and over, respectively. The rate of AD appeared to be slightly higher than that of VD(5.2% vs 4.8%), though not statistically significant. Most of the cases(69%) were mild dementia according to CDR(<1) in these subjects. Conclusions : These results showed that the prevalence rate of dementia among urban elderly in Korea appears to be higher than those of other Asian countries.

• Journal of the korean academy of Pediatric Dentistry
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• v.39 no.3
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• pp.306-313
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• 2012

Class III malocclusion or anterior crossbite is commonly seen in Asian. This problem is easily recognized by dentists and parents. During the primary dentition period, anterior crossbite with functional shift and deep overbite could develop to skeletal protrusive mandible. So, early and proper diagnosis of anterior crossbite which needs prompt treatment is important. These cases showed the early management of crossbite with functional shift in primary dentition using intraoral removable appliance resulting in improvement of intermaxillary relationship. And I analyzed the positional change and the dimensional change during treatment with lateral cephalometric x-ray analysis. Our patients showed vertical dimensional change of lower anterior facial height and clockwise rotation which results crossbite correction in 1 year of treatment period.

• Journal of Life Science
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• v.24 no.2
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• pp.181-185
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• 2014

We identified SNPs (single nucleotide polymorphisms) for endothelial nitric oxide synthase (eNOS) genes in the Korean genome. eNOS is present in the vascular endothelium, platelets, and several other cell types that continuously produce modest amounts of NO. Endothelium-derived NO plays a key role in the regulation of vascular tone, and the impaired effects of NO on the cardiovascular system appear to be responsible for coronary atherosclerosis and thrombosis. In recent studies, a missense variant within exon 7 of the eNOS gene in patients with coronary spastic angina-GAG to GAT substitution, which results in the replacement of glutamic acid by aspartic acid (Glu298Asp [G894T])-has been identified and is known to be significantly associated with coronary spasm. We prepared PCR primers based on sequences in Genbank. Primers were prepared for normal and SNPs separately, as reported for other Asian countries, such as G894T. Their sequences were different only at the 3' ends so that primer extension could only by possible when base pairs between templates and primers matched. We also employed ARMS (Amplification Refractory Mutation System) technology to improve the specificity of the PCR reaction. In conclusion, we were able to demonstrate the eNOS G894A polymorphism in Korean gemone. This study should facilitate research on the cause of myocardial infarction and development on further therapy at the genetic level.

• Journal of fish pathology
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• v.24 no.3
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• pp.255-268
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• 2011

For detection of noroviruses (NVs), we compared various PCR primer sets based on reverse transcription nested PCR (RT-nested PCR) in the water samples from Dong brook in Busan, South Korea. We designed various new primer sets based on the most conserved sequences of the capsid protein gene that react with diverse NVs found in Korea. Designed primer sets (KG1F/KG1R and KG2F/KG2R, named as PNK) for the respective genogroups of NVs, genogroup I and II (GI and GII), were applied to detect NVs in the water samples from Dong brook concentrated with ultracentrifugation. In the application to the water samples, proportion of GI (76.47%) and GII (70.59%) in water samples of Dong brook in RT-nested PCR with the primer sets of this study. However, no significant differences of the proportion of the positive samples were not found between RT-nested PCRs with reported and newly designed primer sets. From the nucleotide sequencing, GI and GII of NVs present in Dong brook were appeared to be the members of 1/2/4/5/9/10 genotypes, and 3/4/5/11/13 genotypes respectively. Appeared genotype 4 of GII known as an one of main genotype found in patients of many Asian countries warned us to consider the risks of norovirus in aquatic environments in southern part of Korea.