• Tuberculosis and Respiratory Diseases
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• v.56 no.5
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• pp.465-484
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• 2004

Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.

• Journal of Preventive Medicine and Public Health
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• v.49 no.5
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• pp.275-287
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• 2016

Objectives: C-reactive protein (CRP), an inflammatory biomarker, has been widely used as a preclinical marker predictive of morbidity and mortality. Although many studies have reported a positive association between CRP and mortality, uncertainty still remains about this association in various populations, especially in rural Korea. Methods: A total of 23 233 middle-aged participants (8862 men and 14 371 women) who were free from cardiovascular disease, cancer, and acute inflammation (defined by a CRP level ${\geq}10mg/L$) were drawn from 11 rural communities in Korea between 2005 and 2011. Blood CRP concentration was analyzed as a categorical variable (low: 0.0-0.9 mg/L; intermediate: 1.0-3.0 mg/L; high: 3.1-9.9 mg/L) as well as a continuous variable. Each participant's vital status through December 2013 was confirmed by death statistics from the National Statistical Office. Cox proportional hazard models were used to assess the independent association between CRP and mortality after adjusting for other risk factors. Results: The total quantity of observed person-years was 57 975 for men and 95 146 for women, and the number of deaths was 649 among men and 367 among women. Compared to the low-CRP group, the adjusted hazard ratio for all-cause mortality of the intermediate group was 1.17 (95% confidence interval [CI], 0.98 to 1.40) for men and 1.27 (95% CI, 1.01 to 1.61) for women, and the corresponding values for the high-CRP group were 1.98 (95% CI, 1.61 to 2.42) for men and 1.41 (95% CI, 1.03 to 1.95) for women. Similar trends were found for CRP evaluated as a continuous variable and for cardiovascular mortality. Conclusions: Higher CRP concentrations were associated with higher mortality in a rural Korean population, and this association was more prominent in men than in women.

• Development and Reproduction
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• v.8 no.1
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• pp.1-9
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• 2004

The potential importance of proteomic approaches has been clearly demonstrated in other fields of human medical research, including liver and heart disease and certain forms of cancer. However, reproductive researches have been applied to proteomics poorly. Proteomics can be defined as the systematic analysis of proteins for their identity, quantity, and function. It could increase the predictability of early drug development and identify non-invasive biomarkers of toxicity or efficacy. Proteome analysis is most commonly accomplished by the combination of two-dimensional gel electrophoresis(2DE) and MALDI-TOF(matrix-assisted laser desorption ionization-time of flight) MS(mass spectrometry) or protein chip array and SELDI-TOF(surface-enhanced laser desorption ionization-time of flight) MS. In addition understanding the possessing knowledge of the developing biomarkers used to assess reproductive biology will also be essential components relevant to the topic of reproduction. The continued integration of proteomic and genomic data will have a fundamental impact on our understanding of the normal functioning of cells and organisms and will give insights into complex cellular processes and disease and provides new opportunities for the development of diagnostics and therapeutics. The challenge to researchers in the field of reproduction is to harness this new technology as well as others that are available to a greater extent than at present as they have considerable potential to greatly improve our understanding of the molecular aspects of reproduction both in health and disease.

• Tuberculosis and Respiratory Diseases
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• v.75 no.1
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• pp.25-27
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• 2013

Carbohydrate antigen 19-9 (CA 19-9) is a widely-used tumor marker in patients with pancreatic cancer. However, some patients with respiratory disease also exhibit elevated serum CA 19-9 levels. We report a case of normalization of elevated serum CA 19-9 levels after treatment of the nodular bronchiectatic form of Mycobacterium abscessus lung disease. A 40-year-old man visited our hospital because of chronic cough and sputum. A computed tomography scan revealed severe bronchiectasis in the right upper and right middle lobes. Nontuberculous mycobacteria were repeatedly isolated and identified as M. abscessus. The serum CA 19-9 level was elevated to 142.35 U/mL (normal range, <37 U/mL). Surgical resection was performed because of failure of sputum conversion after antibiotic treatment. The serum CA 19-9 level returned to the normal range after surgery. This case suggested that serum CA 19-9 levels could be elevated in patients with the nodular bronchiectatic form of M. abscessus lung disease.

• Toxicological Research
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• v.23 no.4
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• pp.321-330
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• 2007

Garlic (Allium sativum L.) with the food supplement material and medicine was used traditionally in Asia and Europe. Epidemiological studies revealed that the intake of garlic reduced incidences of various cancer including digestive system. The present study was designed to investigate the effect of garlic ethanol extract on the development of colonic aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH) in male F344 rats. Five-week-old rats were given four times for two weeks to subcutaneous injections by DMH (30 mg/kg body weight) to induce ACF. The animals were divided into groups that fed diet containing garlic ethanol extract at five different doses (0.1, 0.2, 0.5, 2, 5%), respectively, animals were evaluated for the total number of ACF and total aberrant crypts (AC) per colon detected from methylene blue-stained rat colon. ACF were formed in animals in DMH-treated group. The feeding suppressed potently the appearance ACF in the colon of rats. Especially, fed diet containing garlic ethanol extract at intermediate dose (0.5%) significantly reduced the number of ACF and AC per colon (p < 0.05). Garlic ethanol extract inhibited DMH-induced overexpression of Activator Protein-1 (AP-1) and ${\beta}-catenin$ genes related to cell proliferation that also upregulated the expression of p21Waf1/Cip1 mRNA, a cell cycle-regulating gene. These results suggested that garlic ethanol extract may inhibit ACF formation, ${\beta}-catenin$ gene as the early preneoplastic marker of malignant potential in the process of colon carcinogenesis.

• Journal of Chest Surgery
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• v.43 no.5
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• pp.506-512
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• 2010

Background: This study was designed to evaluate the FDG uptake ratio of mediastinal node and primary tumors using integrated PET/CT imaging combined with Glut-1 expression of the primary tumor in order to predict the N2 status more accurately in NSCLC patients. Material and Method: Patients who underwent integrated PET/CT scanning with a detectable mSUV for both primary tumors and mediastinal lymph nodes were eligible for this study. The FDG uptake ratio between the mediastinal node and the primary tumor was calculated. Result: The average mSUV of primary tumors and mediastinal nodes were, respectively, $7.4{\pm}2.2$ and $4.2{\pm}2.2$ in N2-positive patients and $7.6{\pm}3.7$ and $2.8{\pm}6.9$ in N2-negative patients. The mean FDG uptake ratio of mediastinal node to primary tumor were $0.58{\pm}0.23$ for malignant N2 lymph nodes and $0.45{\pm}0.20$ for benign lymph nodes (p<0.05). Models which combined Glut-1 expression with an FDG ratio have better diagnostic power than models that use the FDG uptake ratio alone. Conclusion: In some patients with a previous history of pulmonary tuberculosis or other inflammatory lung diseases, an FDG uptake ratio combined with Glut-1 expression may be useful in diagnosing mediastinal node metastasis more exactly.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.35 no.3
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• pp.143-154
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• 2013

Purpose: This study was to find efficacy of integrin alpha2 (${\alpha}_2$) and epidermal growth factor receptor (EGFR) as tumor marker of oral squamous cell carcinoma (SCC) and clarify the selective cell death effect of anti-integrin ${\alpha}_2$ and anti-EGFR on SCC cells, additionally testify conjugated gold nanoparticles (GNP) with air plasma for selective cell death of oral SCC. Methods: Expression of integrin ${\alpha}_2$, EGFR on human SCC cells (SCC25) were examined by western blot. SCC25 cells were treated with anti-integrin ${\alpha}_2$, anti-EGFR and analysed by Hemacolor staining, immunoflorescence staining, FACS flow cytometry. Conjugated GNP with integrin ${\alpha}_2$, EGFR antibody were treated by air plasma on SCC cells. Results: Integrin ${\alpha}_2$ and EGFR were over-expressed on SCC25 cells than normal lung WI-38 cells. The cell viability rate of SCC25 cells treated with anti-integrin ${\alpha}_2$, anti-EGFR was lower than WI-38 cells. The concentration changes of nucleus, releasing cytochrome c and apoptosis inducing factor (AIF) from mitochondria to cytosol were observed. The changes of proteins related with apoptosis were observed. Increase of bax, bcl-xL, activation of caspase-3, -7, -9, and fragmentation of PARP, DFF45 and decrease of lamin A/C in SCC25 cells were observed. In FACS, increase of sub-$G_1$ and S phase was observed. Cell cycle related proteins, Such as cyclin D1, cyclin dependent kinase (CDK) 4, cyclin A, cyclin E, CDK 2, p27 were decreased. After SCC25 cells treated with conjugatged GNP-Integrin ${\alpha}_2$, GNP-EGFR, additionally air plasma, the cell death rate was significantly increased. Conclusion: Integrin ${\alpha}_2$, EGFR were over-expressed in oral SCC cells. Anti-integrin ${\alpha}_2$, anti-EGFR in SCC25 cells induced apoptosis selectively. When GNP-anti integrin ${\alpha}_2$, GNP-anti EGFR were treated with air plasma on SCC25 cells, cancer cells were died more selectively. GNP-anti integrin ${\alpha}_2$, GNP-anti EGFR with air plasma could be treatment choice of oral SCC.

• Korean Journal of Clinical Laboratory Science
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• v.36 no.2
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• pp.178-184
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• 2004

This research focuses on the overall evaluation of tumor protein (p53) and cell growth marker (Ki-67) in their functions as carcinogenic factors in both a HPV-infected group and in a HPV-noninfected group with the precancerous dysplasia of uterine cervix. Histological grades were determined by the H&E staining and the expression level of p53 and Ki-67 were tested by the immunohistochemistry method. The results were as follows. Among the total of 66 cases, p53 (+) was observed in 19 cases (29.0%) from the mild grade group, 22 cases (33.0%) from the moderate grade group, and 19 cases (29.0%) from the severe grade group. The values correlate with the increase of dysplasia intensity in HPV-noninfected group and showed significant correlation (p<0.05), but there were no significant difference from the HPV-infected group. Among a total of 66 cases, the mitotic index of Ki-67 (+) were observed in 19 cases (29.0%) from the mild grade group, 22 cases (33.0%) from the moderate grade group, and 19 cases (29.0%) from the severe grade group. The values were significantly different against dysplasia intensity (p<0.05), but showed no significant difference from HPV infection. After cross comparing the statistical parameters of p53 and ki-67 in their significance, p53 was shown to be statistically significant with Ki-67 while there was no statistically significant difference with Ki-67 (p<0.05). Taken together, tumor protein (p53) and an index of Ki-67 observed in cervical dysplasia and in HPV related dysplasia of cervix uterine did not have any notable significance with HPV infection. The incidence rate of p53, however, had some significant correlation with dysplasia while Ki-67 had no particular statistical significance. As a result, p53 and Ki-67 can be considered as effective diagnostic markers in predicting the disease progression of dysplasia to cervical cancer.

• Journal of Ginseng Research
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• v.13 no.1
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• pp.42-48
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• 1989

The binding of bay region diol-epoxides of polycyclic aromatic hydrocarbons (PAHs) to target tissue DNA is thought to be essential for the initiation of cancer by these compounds. In this study we investigated the effect of polyacetylenes such as panaxynol and panaxydol on the formation of benzo(a)pyreno (BP)-metabolite-DNA adduct in the liver of ICR mice. Treatment of mice by i.p. administration of polyacetylenes produced a marked reduction in BP metabolite binding to DNA in vitro. Following i.v. administration of (3H)BP(300, ${\mu}$Ci/21 nmoles/0.1 nt DMSO) to mice, radioactivity was detected in the DNA of the liver in vivo. The result of tentative identification of the 4 peaks between the two standard markers for high pressure liquid chromatography showed that the peaks. I, II, III, and IV were BP-phenol oxide-DNA adduct (or BP-diol-epoxide-dCyt. adduct), (-) BP$.$diolepoxide I:dGuO adduct, (+) BP-diol-epoxide I: dGuo adduct, and BP-diol-epoxide II:dGuO adduct, respectively. The minor adduct, (-) BP-diol epoxide I: dGuo was reduced to 6971 of the amount of the control, while the major adduct, (+) BP-diolepoxide I: dGuO(peak II) which was produced from (-) BP-7, 8-diol was reduced to 78% of that of the control. The amount of the minor adduct, BP-diol-epoxide II:dGuo adduct(peak IV) which formed from (+) BP-7, 8-diol was 58% of the control. These results show that the panaxydol is more related to inhibition of the formation of the minor ad- ducts than of the major adducts, which were generally produced from ($\pm$) BP-7, 8-dihydro-dials.

• Tuberculosis and Respiratory Diseases
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• v.63 no.2
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• pp.165-172
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• 2007

Background: The pathogenesis of lung cancer includes the accumulation of multiple genetic abnormalities. The CREB-binding protein(CBP) is one of several transcriptional co-activators among various sequence-specific DNA-binding transcription factors. CBP is involved in a wide range of cellular activities, such as DNA repair, cell growth, differentiation, and apoptosis that are suspected of contributing to tumorigenesis. The goal of this study was to evaluate CBP expression in a series of human lung tissues containing normal epithelium, premalignant lesions(hyperplasia and dysplasia) and squamous cell carcinomas. Materials and Methods: Immunohistochemical staining was performed on formalin-fixed paraffin-embedded sections by use of a monoclonal anti-CBP antibody. CBP expression was compared in samples from 120 patients with premalignant and malignant histological types including 20 metaplastic specimens, 40 dysplastic specimens, and 60 squamous cell carcinomas in the lung. Results: CBP expression was seen in 35% (7/20) of the metaplastic specimens. 65% (26/40) of the dysplastic specimens, and 70% (42/60) of the squamous cell carcinomas (p<0.05). According to celluar atypism, CBP expression was 50% (10/20) of the low-grade dysplastic specimens and 80% (16/20) of the high-grade dysplastic specimens(p <0.01). By cellular differentiation, CBP expression was seen in 95% (19/20) of the well differentiated squamous cell carcinomas, 85% (17/20) of the moderately differentiated carcinomas and 30% (6/20) of the poorly differentiated lesions (p <0.05). Conclusion: These results suggest that CBP may have an important role in malignant transformation of precancerous lung lesions and may be a marker for malignancy.