• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2953-2958
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• 2015

Although associations between thioredoxin interacting protein (TXNIP) and cancers have been recognized, the effects of TXNIP on non-small cell lung cancer (NSCLC) prognosis remained to be determined in detail. In addition, while hypoxia is a key characteristic of tumor cell growth microenvironment, the effect of hypoxia on TXNIP expression is controversial. In this study, formaldehyde fixed and paraffin embedded (FFPE) samples of 70 NSCLC patients who underwent resection between January 2010 and December 2011 were obtained. Evaluation of TXNIP and hypoxia inducible factor-$1{\alpha}$ ($HIF-1{\alpha}$) protein expression in FFPE samples was made by immunohistochemistry. By Kaplan-Meier method, patients with high TXNIP expression demonstrated a significantly shorter progression free survival (PFS) compared with those with low TXNIP expression (18.0 months, 95%CI: 11.7, 24.3 versus 23.0 months, 95%CI: 17.6, 28.4, P=0.02). High TXNIP expression level was also identified as an independent prognostic factor by Cox regression analysis (adjusted hazard ratio: 2.46; 95%CI: 1.08, 5.56; P=0.03). Furthermore, TXNIP expression was found to be significantly correlated with $HIF-1{\alpha}$ expression (Spearman correlation=0.67, P=0.000). To further confirm correlations, we established a tumor cell hypoxic culture model. Expression of TXNIP was up-regulated in all three NSCLC cell lines (A549, SPC-A1, and H1299) under hypoxic conditions. This study suggests that hypoxia induces increased TXNIP expression in NSCLC and high TXNIP expression could be a poor prognostic marker.

• Tuberculosis and Respiratory Diseases
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• v.75 no.2
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• pp.52-58
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• 2013

Background: More than half of cases for advanced non-small-cell lung cancer (NSCLC) occur in elderly patients with a median age at diagnosis of 70 years. The aim of our study was to examine the clinical features and prognostic factors contributing to mortality in elderly patients with advanced NSCLC. Methods: Following a retrospective review of clinical data, 122 patients aged 70 years and over with a histopathological diagnosis of locally advanced (stage IIIB, n=32) and metastatic (stage IV, n=90) NSCLC between 2005 and 2011 were enrolled. Results: The median age was 76 years (interquartile range, [IQR], 72-80 years), and 85 (70%) patients were male. Fifty-seven (46%) patients had never smoked, and 17 (19%) were in a malnourished state with a body mass index (BMI) of <$18.5kg/m^2$. The initial treatments included chemotherapy (40%) and radiotherapy (7%), but 57% of the patients received supportive care only. The 1-year survival rate was 32%, and the 3-year survival rate was 4%, with a median survival duration of 6.2 months (IQR, 2.5-15.3 months). Male gender (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.3-3.9; p=0.005), low BMI (HR, 2.3; 95% CI, 1.3-3.9; p=0.004), and supportive care only (HR, 1.9; 95% CI, 1.2-2.9; p=0.007) were independent predictors of shorter survival based on a Cox proportional hazards model. Conclusion: Elderly patients with advanced NSCLC had a poor prognosis, particularly male patients, those with a low BMI, and those who received supportive care only.

• Journal of Gastric Cancer
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• v.2 no.1
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• pp.5-11
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• 2002

Purpose: The purpose of this study is to identify immunohistochemical evidence of lymph-node micrometastasis in histologic node-negative gastric cancer patients and to evaluate the prognostic significance of lymph-node micrometastasis.Materials and Methods: A retrospective study of 50 gastric cancer patients who underwent curative resections from October 1990 to November 1994 was performed. Two consecutive sections were prepared: one for ordinary hematoxylin and eosin staining, and the other for immunohistochemical staining with Pan cytokeratin antibody (Novocastra, UK). In the univariate analysis, the survival rate was calculated using the Life Table Method, and the multivariate analysis was determined using a Cox Proportional HazardsModel. The statistical analyses of the relationships between the clinicopathologic factors and micrometastases were performed by using a Chi-square test. Results: Of 2522 harvested lymph nodes, 81 ($4.1\%$) nodes and 19 ($38\%$) of 50 patients were identified as having lymphnode micrometastases by using immunohistochemical staining for cytokeratin. The incidence of lymph-node micrometastases was significantly higher in diffuse type carcinomas ($54\%$, P=0.024) and in patients with serosal invasion ($52.2\%$, P=0.05). For patients with lymph-node micrometastases (n=19), the 5-year survival rate was significantly decreased ($73.7\%$, P=0.015). The Lauren's classirication (P=0.021) and the depth of invasion (P=0.035) were shown by multivariate analysis to have a significant relationship with the presence of micrometastases. Multivariate analysis revealed that lymph-node micrometastasis was independently correlated with survival in histologic node-negative gastic cancer patients. Conclusion: The presence of cytokeratin detected lymphnode micrometastases correlates with the worse prognosis for patients with histologic node-negative gastric cancer.

• Journal of Gastric Cancer
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• v.4 no.3
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• pp.137-142
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• 2004

Purpose: There have been some controversies over the therapeutic principles of advanced gastric cancer, and the results of treatment have been variable, especially for stage III disease. This study was conducted to define the prognostic factors of stage III gastric cancer. Materials and Methods: This retrospective study was based on the medical records of 179 patients with stage III disease who received a gastrectomy from January 1990 to December 1994. The 5-year survival rate was analyzed according to the age, sex, tumor location, tumor size, Borrmann's type, depth of invasion, lymph-node metastasis, ratio of metastatic lymph nodes, type of surgical resection, extent of lymphnode dissection, curability of resection, postoperative chemotherapy, and pathological stage. The statistical analysis was done by using the Kaplan-Meier method, the log-rank test, and the Cox proportional hazards model. Results: The overall 5-year survival rate was $61.6\%$ the 5-year survival rates according to subgroup were $69.7\%$ for stage IIIa ($100\%$ for $T_{2}N_{2}$, $70.0\%$ for $T_{3}N_{1}$, $68.6\%$ for $T_{4}N_{0}$), and $54.1\%$ for stage IIIb ($T_{3}N_{2}$) (P<0.05). Among various clinicopathologic factors of stage III gastric cancer, the age of the patient, the tumor location, the gross type of tumor, the type of gastric resection, the extent of lymph-node dissection, the curability of resection, and the subgroups of stage III were statistically significant in the univariate survival analysis. The multivariate analysis defined the curability of resection, the extent of lymph-node dissection, the type of operation, the stage of disease, and the age of the patient as independent prognostic factors. Conclusion: A curative surgical resection and an extended lymph-node dissection are thought to be most important for improving the survival rate in stage III gastric cancer patients.

• BMB Reports
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• v.48 no.11
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• pp.618-623
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• 2015

FK506 binding protein 12 (FK506BP) is a small peptide with a single FK506BP domain that is involved in suppression of immune response and reactive oxygen species. FK506BP has emerged as a potential drug target for several inflammatory diseases. Here, we examined the protective effects of directly applied cell permeable FK506BP (PEP-1-FK506BP) on corneal alkali burn injury (CAI). In the cornea, there was a significant decrease in the number of cells expressing pro-inflammation, apoptotic, and angiogenic factors such as TNF-α, COX-2, and VEGF. Both corneal opacity and corneal neovascularization (CNV) were significantly decreased in the PEP-1-FK506BP treated group. Our results showed that PEP-1-FK506BP can significantly inhibit alkali burn-induced corneal inflammation in rats, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors and inflammatory cytokines. These results suggest that PEP-1-FK506BP may be a potential therapeutic agent for CAI.

• Molecules and Cells
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• v.28 no.6
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• pp.529-536
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• 2009

Genome sequencing of the pig is being accelerated because of its importance as an evolutionary and biomedical model animal as well as a major livestock animal. However, information on expressed porcine genes is insufficient to allow annotation and use of the genomic information. A series of expressed sequence tags of 5' ends of five full-length enriched cDNA libraries (SUSFLECKs) were functionally characterized. SUSFLECKs were constructed from porcine abdominal fat, induced fat cells, loin muscle, liver, and pituitary gland, and were composed of non-normalized and normalized libraries. A total of 55,658 ESTs that were sequenced once from the 5′ ends of clones were produced and assembled into 17,684 unique sequences with 7,736 contigs and 9,948 singletons. In Gene Ontology analysis, two significant biological process leaf nodes were found: gluconeogenesis and translation elongation. In functional domain analysis based on the Pfam database, the beta transducin repeat domain of WD40 protein was the most frequently occurring domain. Twelve genes, including SLC25A6, EEF1G, EEF1A1, COX1, ACTA1, SLA, and ANXA2, were significantly more abundant in fat tissues than in loin muscle, liver, and pituitary gland in the SUSFLECKs. These characteristics of SUSFLECKs determined by EST analysis can provide important insight to discover the functional pathways in gene networks and to expand our understanding of energy metabolism in the pig.

• Journal of Preventive Medicine and Public Health
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• v.38 no.2
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• pp.203-207
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• 2005

Objectives: Recently, the American Diabetes Association (ADA) redefined the criteria of prediabetes, which has lowered the diagnostic level of fasting plasma glucose (FPG) from 110 to 125 mg/dl, down to levels between 100 to 125mg/dl. The purpose of this study was to determine the predictive cutoff level of FPG as a risk for the development of diabetes mellitus in Korean men. Methods: A retrospective cohort study was conducted on 11,423 (64.5%) out of 17,696 males $\leq$30 years of age, and who met the FPG of $\leq$125 mg/dl and hemoglobin A1c of $\leq$ 6.4% criteria, without a history of diabetes, and who were enrolled at the screening center of a certain university hospital between January and December 1999. The subjects were followed from January 1999 to December 2002 (mean follow-up duration; 2.3(${\pm}0.7$) years). They were classified as normal (FPG <100mg/dl), high glucose (FPG $\geq$100mg/dl and <110mg/dl) and impaired fasting glucose (FPG $\geq$110mg/dl and $\leq$125mg/dl) on the basis of their fasting plasma glucose level measured in 1999. We compared the incidence of diabetes between the 3 groups by performing Cox proportional hazards model and used receiver operating characteristic analyses of the FPG level, in order to estimate the optimal cut-off values as predictors of incident diabetes. Results: At the baseline, most of the study subjects were in age in their 30s to 40s (mean age, 41.8(${\pm}7.1$) year). The incidence of diabetes mellitus in this study was 1.19 per 1,000 person-years (95% CI=0.68-1.79), which was much lower than the results of a community-based study that was 5.01 per 1,000 person-years. The relative risks of incident diabetes in the high glucose and impaired fasting glucose groups, compared with the normal glucose group, were 10.3 (95% CI=2.58-41.2) and 95.2 (95% CI= 29.3-309.1), respectively. After adjustment for age, body mass index, and log triglyceride, a FPG greater than 100mg/dl remained significant predictors of incident diabetes. Using the receiver operating characteristic (ROC) curve, the optimal cutoff level of FPG as a predictor of incident diabetes was 97.5 mg/dl, with a sensitivity and a specificity of 81.0% and 86.0%, respectively. Conclusion: These results suggest that lowering the criteria of impaired fasting glucose is needed in Korean male adults. Future studies on community-based populations, including women, will be required to determine the optimal cutoff level of FPG as a predictor of incident diabetes.

• Journal of Preventive Medicine and Public Health
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• v.40 no.1
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• pp.23-28
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• 2007

Objectives : Chronic infections with hepatitis B or C and alcoholic cirrhosis are three well-known major risk factors for liver cancer. Diabetes has also been suggested as a potential risk factor. However, the findings of previous studies have been controversial in terms of the causal association. Therefore, the aim of this study was to evaluate the association between serum glucose levels and liver cancer development in a Korean cohort. Methods : Thirty-six liver cancer cases were identified in the Korean Multi-Center Cancer Cohort (KMCC). Baseline information on lifestyle characteristics was obtained via questionnaire. Serum glucose levels were measured at the study's enrollment. Relative risks (RRs) were estimated using a Cox proportional hazard regression model. The adjusting variables included age, gender, smoking history, alcohol consumption, body mass index, and hepatitis B surface antigen (HBsAg) seropositivity. Results : The RRs of serum glucose for liver caner were 1.20 (95% CI = 0.48-2.99) for the category of 100 to 125 mg/dL of serum glucose and 2.77 (95% CI = 1.24-6.18) for the >126 mg/dL serum glucose category (both compared to the <100 mg/dL category). In a subgroup analysis, the RR of serum glucose among those who were both HBsAg seronegative and non-drinkers was 4.46 (95% CI = 1.09-18.28) for those with glucose levels >100 mg/dL. Conclusions : The results of this study suggest that a high level of serum glucose can increase liver cancer risk independently of hepatitis infection and drinking history in Koreans. This study implies that glucose intolerance may be an independent risk factor for liver cancer.

• Journal of Preventive Medicine and Public Health
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• v.41 no.4
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• pp.249-254
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• 2008

Objectives: To investigate whether smoking and the smoking status are predictors of the incident impaired fasting glucose (IFG) or type 2 diabetes in Korean men. Methods: A cohort of 1,717 Korean men without IFG or diabetes, who underwent annual periodic health examinations for 4 years (2002-2006), were retrospectively investigated. IFG and diabetes were defined as a serum fasting glucose concentration of 100-125 mg/dL and more than 126 mg/dL, respectively. Cox's proportional hazards model was used to evaluate the association between smoking and development of IFG or type 2 diabetes. Results: A total of 558 cases (32.5%) of incident IFG and 50 cases (2.9%) of diabetes occurred. After controlling for the potential predictors of diabetes, the relative risk for IFG, compared with the never smokers, was 1.02 (95% CI=0.88 to 1.19) for the ever-smokers, 0.96 (95% CI=0.79-1.16) for those who smoked 1-9 cigarettes/d, 1.15 (95% CI=1.01 to 1.30) for those who smoked 10-19 cigarettes/d, and 1.31 (95% CI=1.10 to 1.57) for those who smoked 20 or more cigarettes/d (the P value for the current smokers was only p<0.002). The respective multivariate adjusted relative risks for type 2 diabetes, compared with the never-smokers, were 1.07 (95% CI=0.64 to 1.92), 1.47 (95% CI=0.71 to 3.04), 1.84 (95% CI=0.92-3.04), and 1.87 (95% CI=1.13-3.67), respectively (the P value for the current smokers was only p=0.004). Conclusions: The smoking status and the number of cigarettes smoked daily are associated with an increased risk for developing IFG or type 2 diabetes in Korean men.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1437-1443
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• 2016

Background: We investigated four factors, height, weight gain since age 20, physical activity, and alcohol drinking, for associations with risk of breast cancer (BC) according to menopausal status, using the latest data of the Japan Collaborative Cohort Study (JACC Study). Materials and Methods: We confined the analysis to 24 areas available of cancer incidence information, excluding women with a previous diagnosis of BC. Baseline data were collected from 38,610 (9,367 premenopausal, and 29,243 postmenopausal) women during 1988 and 1990. The study subjects were followed-up at the end of 2009, and 273 (84 premenopausal, and 189 postmenopausal) cases of BC were newly diagnosed in 501,907 person-years. The Cox model was used to estimate a hazards ratio (HR) and its 95% confidence interval (CI) of BC risk. Results: As a result of the multivariate analysis adjusting for age at baseline survey, age at menarche, number of live births, and, age at first delivery, weight gain since age 20 of 6.7 kg-9.9 kg, and ${\geq}10.0kg$ were significantly associated with increased risk for postmenopausal BC (HR=2.48, 95% CI 1.40-4.41, and, HR=2.94, 95% CI 1.84-4.70, respectively). Significantly increased trend of BC risk was also observed in weight gain since age 20 (p for trend, p<0.001). Amount of ethanol intake per day${\geq}15.0g$ was significantly associated with increased risk for postmenopausal BC in the multivariable-adjusted analysis (HR=2.74, 95% CI 1.32-5.70). Conclusions: Higher weight gain in adulthood and larger amounts of ethanol intake were significantly associated with increased risk of BC in Japanese postmenopausal women. None of the investigated factors were significantly associated with BC risk in Japanese premenopausal women.