Purpose: Pancreatic cancer (PC) is one of the most lethal cancers worldwide, but there are currently no effective treatments. The DNA damage response (DDR) is under investigation for the development of novel anti-cancer drugs. Since DNA repair pathway alterations have been found frequently in PC, the purpose of this study was to test the DDR-targeting strategy in PC using WEE1 and ATM inhibitors. Materials and Methods: We performed in vitro experiments using a total of ten human PC cell lines to evaluate antitumor effect of AZD1775 (WEE1 inhibitor) alone or combination with AZD0156 (ATM inhibitor). We established Capan-1–mouse model for in vivo experiments to confirm our findings. Results: In our research, we found that WEE1 inhibitor (AZD1775) as single agent showed anti-tumor effects in PC cells, however, targeting WEE1 upregulated p-ATM level. Here, we observed that co-targeting of WEE1 and ATM acted synergistically to reduce cell proliferation and migration, and to induce DNA damage in vitro. Notably, inhibition of WEE1 or WEE1/ATM downregulated programmed cell death ligand 1 expression by blocking glycogen synthase kinase-3β serine 9 phosphorylation and decrease of CMTM6 expression. In Capan-1 mouse xenograft model, AZD1775 plus AZD0156 (ATM inhibitor) treatment reduced tumor growth and downregulated tumor expression of programmed cell death ligand 1, CMTM6, CD163, and CXCR2, all of which contribute to tumor immune evasion. Conclusion Dual blockade of WEE1 and ATM might be a potential therapeutic strategy for PC. Taken toget

PURPOSE: The purpose of this study was to validate the Korean version of the TNO-AZL Preschool Children Quality of Life (TAPQOL) questionnaire for children aged 18-60 months. METHODS: The participants were 223 mothers of healthy children from nurseries and kindergartens, and 54 mothers of hospitalized children from a university children's hospital in Korea. Data were collected in 2011. Principal component factor analysis and known-groups method were used to confirm construct validity, and internal consistency was used to determine reliability. RESULTS: According to the factor analysis, 11 factors with an eigenvalue over 1 were extracted, and these factors explained 73.5% of the variance. All dimensions except two had Cronbach's alpha coefficients greater than .7. The mean TAPQOL scores of the hospitalized group were significantly lower than those of the healthy group (p=.001) for all four functions (physical, emotional, social, and cognitive). CONCLUSIONS: The TAPQOL showed acceptable validity and reliability, and can be used to measure children's health-related quality of life in Korea, and can be considered for use in other Asian countries.
Asian Continental Ancestry Group ; Child* ; Child, Hospitalized ; Child, Preschool ; Humans ; Korea ; Mothers ; Nurseries ; Quality of Life* ; Reproducibility of Results ; Translations ; Surveys and Questionnaires

This study was performed to identify association between nutritional status and health risks of the elderly. This was a cross-sectional study involving low income elderly women in Gwangju, Korea (> or = 65y, n = 92). Socio-demographics, life style characteristics, health conditions, dietary intakes based on 24h-recall method, anthropometric measures, and clinical biochemistry parameters were examined. Anthropometric and clinical parameters included wt, ht, waist, hip, body protein, body fat, abdominal fat, total cholesterol, HDL-cholesterol, triglyceride, total protein, albumin, hemoglobin, hematocrit, fasting blood glucose, ferritin, IL-2, IL-6, TNF-alpha, CRP, TAS, TBARS, systolic blood pressure, and diastolic blood pressure. The subjects were divided into three groups based on age (65-74y, 75-84y, 85y < or =) and were divided into two groups according to the sum of the Nutrition Screening Initiative (NSI) checklist score (adequate nutritional status, NSI score < or = 3; at risk of malnutrition, NSI score > 3). Mean and frequency of variables were estimated. Analysis of Variance, Tukey test, Chi-square test, and Multiple linear regression analyses were performed. Mean BMI and body fat were 25.1 kg/m2 and 40.0%, respectively. However, for over 80% of subjects, the intakes of energy, fiber, thiamin, riboflavin, niacin, folate, Ca, K, and Zn were less than the Korean DRI (EAR or AI). The subjects who had lower NSI score tended to have better health status, eat meals frequently, have less depression, and exercise regularly. The subjects who had higher NSI score tended to have tooth problems, to eat alone most of time, and to be physically unable to cook or feed. Serum IL-6 and TNF-alpha were significantly related with nutritional status which suggested higher tendency of inflammatory response. Serum IL-2, TAS, and glucose were significantly correlated with body fat (%) or abdominal fat (%). These results suggest that improving the nutritional status, increasing regular exercise, maintaining normal weight are beneficial to health care of low income elderly women.
Abdominal Fat ; Adipose Tissue ; Aged ; Biochemistry ; Blood Glucose ; Blood Pressure ; Checklist ; Cholesterol ; Cross-Sectional Studies ; Delivery of Health Care ; Depression ; Fasting ; Female ; Ferritins ; Folic Acid ; Glucose ; Hematocrit ; Hemoglobins ; Hip ; Humans ; Interleukin-2 ; Interleukin-6 ; Korea ; Life Style ; Linear Models ; Malnutrition ; Mass Screening ; Meals ; Niacin ; Nutritional Status ; Riboflavin ; Thiobarbituric Acid Reactive Substances ; Tooth ; Tumor Necrosis Factor-alpha

No abstract available.
Carcinoma, Basal Cell ; Nose

This study investigated the effects of soyoligosaccharide consumption on lipid profile of plasma, liver and feces and immune responses in Sprague-Dawley male rats. Sixty male Sprague-Dawley rats 4-wk-old were provided the soyoligosaccharide containing diets for 4 weeks (0, 100 g/kg diet); each of these diets was supplemented with either 70 or 200 g fat/kg diet, giving a total of 4 experimental groups. The effect of weight reduction was most significantly observed in the group fed low fat and soyoligosacchairde diet. The plasma total lipid and cholesterol contents were not changed by either fat proportion or soyoligosaccharide supplementation in the diets. Also the plasma triglyceride lowering effect by soyoligosaccharide was not observed in rats fed either low fat or high fat diet. However, the significant decrease in TG contents was found with rats fed high fat diets compared to the control/no soyoligosaccharide diet. Elevation of plasma LDL-cholesterol and reduction of HDL-cholesterol by feeding high fat diet was not altered by supplementing soyoligosaccharide. This was also applied to the liver lipid profiles. The significant increases in liver total lipid, triglycerides and cholesterol by high fat diet was not abolished by feeding soyoligosaccharide. However, the desirable effects of feeding soyoligosaccharide were found with total lipid and cholesterol excretion through feces in rats fed high fat diets. Immune organ weights and spleen cell proliferations did not affected by experimental diets. These results demonstrated that soyoligosaccharide intakes increased the lipid output via feces, especially in rats fed the high fat diet, but more researches are needed on immune responses.
Animals ; Cholesterol ; Diet* ; Diet, High-Fat ; Feces ; Humans ; Lipid Metabolism* ; Liver ; Male ; Organ Size ; Plasma ; Rats* ; Rats, Sprague-Dawley ; Spleen ; Triglycerides ; Weight Loss

PURPOSE: This study was conducted to identify risk factors in hospitalized children, and to develop and validate a fall-risk assessment tool for hospitalized children. METHODS: A retrospective chart review was performed at one university children's hospital, and an analysis was done of the characteristics of all patients who fell during a 44-month period (n=48). These patients were compared with another 149 hospitalized children who did not fall. RESULTS: Significant predictors of falls as identified in a multivariate logistic regression analyses were age of less than 3 years old, neurological diagnosis including epilepsy, children's dependency of ADL, physical developmental delay, multiple usage of fall-risk-increasing drugs. The respective odds ratios ranged from 2.4 to 7.1 with 95% confidence interval (p<0.05). Accordingly, defining patients with either 5 risk factors as fall-prone hospitalized children provided a sensitivity of 93.6% and specificity of 16.2%. CONCLUSION: The results show that this tool has an acceptable level of sensitivity to assess the risk factors of fall in hospitalized children even though the specificity was low, suggesting that this tool may enable nurses to predict the risk level of childhood falls, and develop preventive strategies against pediatric falls in children's units.
Accidental Falls ; Activities of Daily Living ; Child ; Child, Hospitalized* ; Diagnosis ; Epilepsy ; Humans ; Logistic Models ; Odds Ratio ; Retrospective Studies ; Risk Factors ; Sensitivity and Specificity

Although congenital syphilis can be prevented with prenatal screening, the disease remains problematic. Currently, there are no cases that describe hematuria and pneumonia related to congenital syphilis. We report a case of congenital syphilis that involved nephrotic syndrome and pneumonia alba in a 22-day-old male infant whose mother did not receive adequate prenatal care. The congenital syphilis diagnosis was confirmed with a serologic test and the patient recovered with penicillin treatment. Clinical findings may be subtle in neonates and delayed recognition occurs frequently, thus complete prenatal screening is critical for congenital syphilis prevention. Immediate serologic testing should be performed to obtain a differential diagnosis if an infant is delivered by a mother that has not received appropriate prenatal examinations.
Diagnosis ; Diagnosis, Differential ; Exanthema* ; Hematuria* ; Humans ; Infant ; Infant, Newborn ; Male ; Mothers ; Nephrotic Syndrome ; Penicillins ; Pneumonia* ; Prenatal Care ; Prenatal Diagnosis ; Serologic Tests ; Syphilis, Congenital*

Purpose: Currently, the DNA damage response (DDR) pathway represents a key target for new cancer drug development. Advanced biliary tract cancer (BTC) has a poor prognosis because of the lack of efficacious treatment options. Although DNA repair pathway alterations have been reported in many patients with BTC, little is known regarding the effects of DDR-targeted agents against BTC. Materials and Methods: In this study, nine BTC cell lines were exposed to the WEE1 inhibitor (AZD1775). In vitro, MTT assay, colony-forming assay, cell cycle analysis, phospho-histone H3 staining assay, Transwell migration assay, and western blot were performed. Then, to enhance the antitumor effect of AZD1775, the combination treatment of WEE1 inhibitor and ataxia telangiectasia mutated and Rad3 related (ATR) inhibitor (AZD6738) was conducted using MTT assay and comet assay. Finally, HuCCT-1 and SNU2670 xenograft models were established to confirm the anti-tumor effect of AZD1775 alone. Furthermore, the combination treatment was also evaluated in SNU2670 xenograft models. Results: AZD1775 blocked the phosphorylation of CDC2 and CDC25C in all cell lines, but significantly increased apoptosis and S phase arrest in sensitive cells. However, increased p-ATR and phosphorylated ataxia telangiectasia mutated levels were observed in less sensitive cells. In addition, in vitro and in vivo data illustrated that AZD1775 combined with AZD6738 exerted more potent anti-tumor effects than either drug alone. Although WEE1 inhibition has promising anti-tumor effects in some BTC cells, the addition of ATR inhibitors could enhance its efficacy. Conclusion Taken together, this study supports further clinical development of DDR-targeted strategies as monotherapy or combination regimens for BTC.

PURPOSE: The soluble programmed death-ligand 1 (sPDL1) has immunosuppressive activity and is a candidate biomarker for immuno-oncology drug development. In this study, we measured sPDL1 at pre- and post-chemotherapy and at disease progression to uncover the dynamics of sPDL1 during treatment in biliary tract cancer (BTC) patients. MATERIALS AND METHODS: From 90 BTC patients (training cohort, 53; validation cohort, 37) who were candidates for palliative first-line chemotherapy, blood was collected at pre- and post-chemotherapy (at the time of best response) and at disease progression. The sPDL1 levels were measured using an enzyme-linked immunosorbent assay. Responses to chemotherapy, overall survival (OS), and other prognostic factors including the neutrophil-lymphocyte ratio (NLR) were analyzed. RESULTS: The OS of all patients was 11.5 months (confidence interval [CI], 9.7 to 16.2). The best response was complete response in seven (7.8%), partial response in 20 (22.2%), stable disease in 52 (57.8%), and disease progression (PD) in 11 patients (12.2%). Patients with high pre-chemotherapy sPDL1 (≥ 1.30 ng/mL) showed worse OS than patients with low prechemotherapy sPDL1 (9.1 months vs. 12.5 months, p=0.003). In multivariate analyses, high pre-chemotherapy sPDL1 (hazard ratio [HR], 1.96; 95% CI, 1.2 to 3.9; p=0.011) and high pre-chemotherapy NLR (HR, 1.82; 95% CI, 1.1 to 3.0; p=0.020) were independent poor prognostic factors for OS. At the time of PD, sPDL1 was increased significantly compared with pre-chemotherapy sPDL1 (1.59 ng/mL vs. 0.72 ng/mL, p=0.003). CONCLUSION: The sPDL1 at pre-chemotherapy confers the prognostic value for OS in BTC patients under palliative chemotherapy. The dynamics of sPDL1 during chemotherapy correlate with disease burden and have prognostic value.
Biliary Tract Neoplasms ; Biomarkers ; Cohort Studies ; Disease Progression ; Drug Therapy ; Enzyme-Linked Immunosorbent Assay ; Humans ; Multivariate Analysis ; Prognosis

PURPOSE: The DNA damage response (DDR) is a multi-complex network of signaling pathways involved in DNA damage repair, cell cycle checkpoints, and apoptosis. In the case of biliary tract cancer (BTC), the strategy of DDR targeting has not been evaluated, even though many patients have DNA repair pathway alterations. The purpose of this study was to test the DDR-targeting strategy in BTC using an ataxia-telangiectasia and Rad3-related (ATR) inhibitor. MATERIALS AND METHODS: A total of nine human BTC cell lines were used for evaluating anti-tumor effect of AZD6738 (ATR inhibitor) alone or combination with cytotoxic chemotherapeutic agents through MTT assay, colony-forming assays, cell cycle analyses, and comet assays. We established SNU478-mouse model for in vivo experiments to confirm our findings. RESULTS: Among nine human BTC cell lines, SNU478 and SNU869 were the most sensitive to AZD6738, and showed low expression of both ataxia-telangiectasia mutated (ATM) and p53. AZD6738 blocked p-Chk1 and p-glycoprotein and increased γH2AX, a marker of DNA damage, in sensitive cells. AZD6738 significantly increased apoptosis, G2/M arrest and p21, and decreased CDC2. Combinations of AZD6738 and cytotoxic chemotherapeutic agents exerted synergistic effects in colony-forming assays, cell cycle analyses, and comet assays. In our mouse models, AZD6738 monotherapy decreased tumor growth and the combination with cisplatin showed more potent effects on growth inhibition, decreased Ki-67, and increased terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling than monotherapy with each drug. CONCLUSION: In BTC, DDR targeting strategy using ATR inhibitor demonstrated promising antitumor activity alone or in combination with cytotoxic chemotherapeutic agents. This supports further clinical development of DDR targeting strategy in BTC.
Animals ; Apoptosis ; Ataxia Telangiectasia ; Biliary Tract Neoplasms ; Biliary Tract ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Line ; Cisplatin ; Comet Assay ; DNA Damage ; DNA Repair ; DNA ; Humans ; Mice ; P-Glycoprotein