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Irinotecan, an analogue of camptothecin, is frequently used as a single agent or in combination with other anticancer drugs for the treatment of colorectal cancer. However, the drug resistance of tumors is a major obstacle to successful cancer treatment. In this study, we established that cells acquire chronic resistance to irinotecan. We profiled their differential gene expression using microarray. After gene ontology (GO) and KEGG pathway analysis of the microarray data, we specifically investigated whether Sestrin3 could decrease irinotecan resistance. Our results revealed that Sestrin3 enhanced the anticancer effect of irinotecan in vitro in LoVo cells that had acquired resistance to irinotecan. Irinotecan-resistant LoVo cells showed lower reactive oxygen species (ROS) production than their irinotecan-sensitive parental cells. ROS production was increased by Sestrin3 knockdown in irinotecan-resistant LoVo cells. Our results indicate that Sestrin3 might be a good target to develop therapeutics that can help to overcome resistance to irinotecan. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) which is caused by obesity and insulin resistance, is well known for its predictive capability for the risk of type 2 diabetes mellitus and cardiovascular disease. The development of MetS is associated with multiple genetic factors, environmental factors and lifestyle. We performed a genome-wide association study to identify single-nucleotide polymorphism (SNP) related to MetS in large Korean population based samples of 1,362 subjects with MetS and 6,061 controls using the Axiom® Korean Biobank Array 1.0. We replicated the data in another sample including 502 subjects with MetS and 1,751 controls. After adjusting for age and sex, rs662799 located in the APOA5 gene were significantly associated with MetS. 15 SNPs in GCKR, C2orf16, APOA5, ZPR1, and BUD13 were associated with high triglyceride (TG). 14 SNPs in APOA5, ALDH1A2, LIPC, HERPUD1, and CETP, and 2 SNPs in MTNR1B were associated with low high density lipoprotein cholesterol (HDL-C) and high fasting blood glucose respectively. Among these SNPs, 6 TG SNPs: rs1260326, rs1260333, rs1919127, rs964184, rs2075295 and rs1558861 and 11 HDL-C SNPs: rs4775041, rs10468017, rs1800588, rs72786786, rs173539, rs247616, rs247617, rs3764261, rs4783961, rs708272, and rs7499892 were first discovered in Koreans. Additional research is needed to confirm these 17 novel SNPs in Korean population. [ABSTRACT FROM AUTHOR]

Background: Changes in head and neck position may significantly affect the performance of supraglottic airway devices (SADs) by altering the pharyngeal structure. Purpose: This systematic review and meta-analysis aimed to elucidate the effect of changes in head and neck position on performance of SADs. Data source: Bibliographic databases, including PubMed, EMBASE, the Cochrane library, and the Web of Science. Study eligibility criteria: Prospective studies investigating the effects of head and neck positions on the performance of SADs. Methods: A random effect model was applied in the all analyses. Subgroup analysis was performed according to the type of device and the age of patient. The oropharyngeal leak pressure was the primary outcome measure. Secondary outcome measures included peak inspiratory pressure, fibreoptic view, and ventilation score (PROSPERO, CRD42017076971). Results: Seventeen studies met the eligibility criteria. Overall, the oropharyngeal leak pressure significantly increased (mean difference 4.07 cmH2O; 95% confidence interval 3.30 to 4.84) during neck flexion with adverse effects on ventilation and fibreoptic view. Conversely, the oropharyngeal leak pressure decreased (mean difference −4.05; 95% confidence interval −4.90 to −3.20) during neck extension with no significant effect on ventilation or fibreoptic view. Rotation of the head and neck did not significantly affect SAD performance. Conclusions: The reduced oropharyngeal leak pressure in the extended neck position was not associated with impaired ventilation except with the air-Q self-pressurizing airway. The flexed neck position significantly worsens ventilation and the alignment between the SAD and glottis despite improving the seal except with the air-Q self-pressurizing airway and LMA Proseal. [ABSTRACT FROM AUTHOR]

Epidemiologic evidence indicates that the prevalence and severity of coronary artery disease vary depending on ethnicity. In this study, a genome-wide association study for coronary artery calcification (CAC) was performed in a Korean population-based sample of 400 subjects without prior coronary artery disease and replicated in another of 1,288 subjects. CAC score, as assessed by multi-detector computed tomography, was evaluated in volunteers for screening purposes as part of a routine health examination. CAC score greater than the 90th percentile across the age in each sex group was considered severe CAC. Single nucleotide polymorphisms (SNPs) associated with severe CAC after adjusting for age, sex, hypertension, and diabetes were investigated using the additive model of logistic regression. One SNP (rs10757272 in the intronic region of the CDKN2B-AS1 gene in chromosome 9p21.3) met Bonferroni correction in the discovery set (p = 7.55E-08) and was also significant in the validation set by TaqMan assay (p = 0.036). Subjects with rs10757272 were found to have an increased odds ratio (OR) of having severe CAC in multivariate logistic regression analysis after adjusting for age, sex, hypertension, and diabetes (adjusted OR 3.24 and 95% CI 2.11–4.97). In conclusion, SNP rs10757272 in chromosome 9p21.3 was associated with severe CAC based on age and sex in an asymptomatic community-based Korean population. Therefore, it was associated with promotion of coronary artery calcification in subclinical state. [ABSTRACT FROM AUTHOR]

Obesity, particularly abdominal obesity, might be related to decreased lung function. We aimed to investigate whether obesity indices are associated with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in asymptomatic non-smokers through a longitudinal cohort study. The clinical records of 1,145 subjects (428 males, mean age 52.3 years) who underwent a comprehensive health evaluation, including spirometry and abdominal fat computed tomography, at least twice between 2007 and 2014 were retrospectively reviewed and analysed. The mean follow-up period was 1,105 days (over 3.0 years). The baseline total adipose tissue (TAT) and visceral adipose tissue (VAT) were inversely associated with both FEV1 and FVC (P < 0.05). The longitudinal study found that increasing TAT and VAT were significantly related to decreasing FEV1 and FVC, whereas decreasing TAT and VAT were related to increasing FEV1 and FVC in both males and females (P < 0.05). The strength and consistency of these associations were clearer in males than in females. However, no significant relationship was found between changes in subcutaneous adipose tissue and changes in lung function. In Korean non-smokers, longitudinal changes in abdominal visceral fat were found to be inversely related to changes in lung function over a mean period of three years. These results suggest that decreasing abdominal visceral obesity could increase lung function despite ageing. [ABSTRACT FROM AUTHOR]

Background and aim: Tumor burden is important to predict clinical behaviors of cancer such as lymph node metastasis (LNM). Tumor size has been used as a parameter of tumor burden such as indication of endoscopic resection in early gastric cancer (EGC) to predict LNM. Thus, we aimed to investigate whether tumor area can be more helpful to predict clinical behaviors than longest diameter of tumor in EGC. Patients and methods: 3,059 patients who underwent gastrectomy for EGC were reviewed retrospectively. Tumor area was calculated by multiplying long and short diameter of the tumor in surgical specimen. Longest diameter means maximal longitudinal diameter of tumor in specimen. Clinicopathologic features were compared between longest diameter and area using area under receiver operating characteristic (AUROC) curves. Results: Longest diameter and area of tumor showed a strong correlation (correlation coefficient 0.859, p<0.01). The cutoff value for prediction of LNM was 20 mm of longest diameter of tumor and 270 mm2 of tumor area. There was no significant difference between longest diameter and area for prediction of LNM (AUC 0.850 vs. 0.848, respectively). In differentiated-type EGC and undifferentiated-type EGC, there was no significant difference between longest diameter and area for prediction of LNM. Among mucosal or submucosal cancer prediction value of LNM between longest diameter and area was not significantly different. Conclusion: Tumor area may not be more helpful to predict LNM than longest diameter in EGC. Therefore, the longest diameter of tumor may be sufficient as an indicator of tumor burden in EGC. [ABSTRACT FROM AUTHOR]

Background: The presence of ulcer in early gastric cancer (EGC) is important for the feasibility of endoscopic resection, only a few studies have examined the clinicopathological implications of endoscopic ulcer in EGC. Objectives: To determine the role of endoscopic ulcer as a predictor of clinical behaviors in EGC. Methods: Data of 3,270 patients with EGC who underwent surgery between January 2005 and December 2012 were reviewed. Clinicopathological characteristics were analyzed in relation to the presence and stage of ulcer in EGC. Based on endoscopic findings, the stage of ulcer was categorized as active, healing, or scar. Logistic regression analysis was performed to analyze factors associated with lymph node metastasis (LNM). Results: 2,343 (71.7%) patients had endoscopic findings of ulceration in EGC. Submucosal (SM) invasion, LNM, lymphovascular invasion (LVI), perineural invasion, and undifferentiated-type histology were significantly higher in ulcerative than non-ulcerative EGC. Comparison across different stages of ulcer revealed that SM invasion, LNM, and LVI were significantly associated with the active stage, and that these features exhibited significant stage-based differences, being most common at the active stage, and least common at the scar stage. The presence of endoscopic ulcer and active status of the ulcer were identified as independent risk factors for LNM. Conclusions: Ulcerative EGC detected by endoscopy exhibited more aggressive behaviors than non-ulcerative EGC. Additionally, the endoscopic stage of ulcer may predict the clinicopathological behaviors of EGC. Therefore, the appearance of ulcers should be carefully evaluated to determine an adequate treatment strategy for EGC. [ABSTRACT FROM AUTHOR]

Background: Treatment strategy for early gastric cancer depends on the probability of lymph node metastasis. The aim of this study is to develop a nomogram predicting lymph node metastasis in early gastric cancer using clinicopathological factors and biomarkers. Methods: A literature review was performed to identify biomarkers related to lymph node metastasis in gastric cancer. Seven markers were selected and immunohistochemistry was performed in 336 early gastric cancer tissues. Based on the multivariable analysis, a prediction model including clinicopatholgical factors and biomarkers was developed, and benefit of adding biomarkers was evaluated using the area under the receiver operating curve and net reclassification improvement. Functional study in gastric cancer cell line was performed to evaluate mechanism of biomarker. Results: Of the seven biomarkers studied, α1 catenin and CD44v6 were significantly associated with lymph node metastasis. A conventional prediction model, including tumor size, histological type, lymphatic blood vessel invasion, and depth of invasion, was developed. Then, a new prediction model including both clinicopathological factors and CD44v6 was developed. Net reclassification improvement analysis revealed a significant improvement of predictive performance by the addition of CD44v6, and a similar result was shown in the internal validation using bootstrapping. Prediction nomograms were then constructed based on these models. In the functional study, CD44v6 was revealed to affect cell proliferation, migration and invasion. Conclusions: Overexpression of CD44v6 was a significant predictor of lymph node metastasis in early gastric cancer. The prediction nomograms incorporating CD44v6 can be useful to determine treatment plans in patients with early gastric cancer. [ABSTRACT FROM AUTHOR]