Targeting Gli1, a potential diagnostic marker of ESCC stem cells, will have a profound therapeutic and prognostic value.

Background: Online haemodiafiltration (OL-HDF) may improve middle molecular clearance in contrast to conventional haemodialysis (HD). However, OL-HDF requires higher convective flows and cannot sufficiently remove large middle molecules. This study evaluated the efficacy of a medium cutoff (MCO) dialyser in removing large middle molecular uraemic toxins and compared it with that of conventional high-flux (HF) dialysers in HD and predilution OL-HDF. Methods: Six clinically stable HD patients without residual renal function were investigated. Dialyser and treatment efficacies were examined during a single midweek treatment in three consecutive periods: 1) conventional HD using an HF dialyser, 2) OL-HDF using the same HF dialyser, and 3) conventional HD using an MCO dialyser. Treatment efficacy was assessed by calculating the reduction ratio (RR) for β2-microglobulin (β2M), myoglobin, κ and λ free light chains (FLCs), and fibroblast growth factor (FGF)-23 and measuring clearance for FLCs. Results: All three treatments showed comparable RRs for urea, phosphate, creatinine, and uric acid. MCO HD showed greater RRs for myoglobin and λFLC than did HF HD and predilution OL-HDF (myoglobin: 63.1 ± 5.3% vs. 43.5 ± 8.9% and 49.8 ± 7.3%; λFLC: 43.2 ± 5.6% vs. 26.8 ± 4.4% and 33.0 ± 9.2%, respectively; P < 0.001). Conversely, predilution OL-HDF showed the greatest RR for β2M, whereas MCO HD and HF HD showed comparable RRs for β2M (predilution OL-HDF vs.

Non-alcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation of metabolic syndrome and is associated with cardiovascular outcomes. We investigated whether NAFLD was associated with coronary artery calcification (CAC) in participants without a previous history of cardiovascular disease and whether this association differed according to sex and obesity status after adjustment for other atherosclerosis risk factors, alcohol intake, and liver enzyme levels. Among 67,441 participants, data from 8,705 participants who underwent a fatty liver status and CAC assessment during routine health screening were analysed. CAC scores were calculated using computed tomography. NAFLD was diagnosed in patients with evidence of liver steatosis on ultrasonography. Obesity was defined as a body mass index of ≥25 kg/m 2. Multivariate analysis showed a significant association between NAFLD and CAC in non-obese participants (odds ratio, 1.24 [95% confidence interval, 1.01-1.53]), whereas NAFLD and CAC were not associated in obese participants. Interaction analysis showed that the association between NAFLD and CAC was influenced by sex and obesity. Subgroup analysis revealed a significant association between NAFLD and CAC in non-obese male participants (odds ratio, 1.36 [1.07-1.75]), but not in female participants. Our study indicates that non-obese men with NAFLD are prone to CAC. Cardiovascular disease (CVD) is a major cause of death, and its contribution to the overall disease burden is expected to increase. Therefore, there have been worldwide efforts to identify cardiovascular risk factors 1,2. Obesity is a well-established risk factor for CVD and mortality 3 ; however, recent studies have reported the localized distribution of body fat rather than overall obesity 4,5. In one study, regional fat distribution was shown to have a significant association with the risk of coronary heart disease after adjusting for body mass index (BMI) 4. Non-alcoholic fatty liver disease (NAFLD) can progress to liver cirrhosis and liver cancer, but its clinical manifestation is not confined to the liver. Moreover, it has been associated with an increased prevalence and incidence of CVD 6-8. NAFLD is a highly prevalent metabolic abnormality closely linked to the overweight and obesity epidemic 8-10. In tertiary liver centres, a majority of patients with NAFLD also have an increased BMI, but approximately 1 out of 8 NAFLD patients has normal BMI 11. Globally, the prevalence of NAFLD in the non-obese population has been widely reported, ranging from 3% to 30% 12. Coronary artery calcification (CAC) is a non-invasive predictor of the burden of coronary atherosclerosis and is evaluated using computed tomography (CT). CAC scores have been reported to be associated with increased

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The down-regulation of CD99 protein expression is a critical event in the progress of TCC, especially in advanced stage, and it can be explained by the presence of CD99 gene promoter hypermethylation in TCC. And both CD99 protein expression and gene promoter hypermethylation have clinical significance and implication for the diagnosis and target therapy for TCC.

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Background: Sarcopenia involves an age-related decline in skeletal muscle mass with functional disability or low muscle strength. Vascular calcification (VC) occurs commonly in patients with chronic kidney disease, in whom it is associated with cardiovascular disease. We aimed to investigate the correlations of low muscle mass with the quantified vascular calcification score (VCS) of the arm of vascular access, as well as whether low muscle mass is associated with the incidence of vascular access failure. Methods: The VCS was measured on non-contrast, arm computed tomography using the Agatston method. The lower muscle mass (LMM) group comprised subjects whose skeletal muscle mass of the lower extremities, as measured using bioelectrical impedance, was lower than the median. Higher VC was defined as a score of 500 or above, corresponding to the highest 40% of VCS. The relationship between LMM and VC was explored using univariate and multivariate logistic regression analyses. Results: Seventy-five patients were included, of whom forty-two (56.0%) were men. The median age was 64 years (interquartile range 58–72 years). Of the 75 patients, 73 satisfied the diagnostic criteria for sarcopenia. The median hemodialysis vintage was 49.4 months (range 32.1–99.2 months). No significant differences were found between the non-LMM and LMM groups in sex, end-stage renal disease etiology, and type of vascular access, although the LMM group showed significantly older age and hemodialysis vintage. LMM presented a significant association with VC (hazard ratio (HR) 3.562; 95% CI, 1.341–9.463; p = 0.011). Upon adjustment for hemodialysis vintage, diabetes, and systolic blood pressure, LMM demonstrated an independent association with VC (HR, 10.415; 95% CI, 2.357–46.024; p = 0.002). The risk of vascular access failure was higher in the LMM group (HR, 3.652; 95%, CI 1.135–11.749; p = 0.03). VC was a full mediator in the relationship of LMM with recurrent vascular access failure. Conclusions: We quantified LMM via bioimpedance analysis and found a heretofore-unreported association between LMM and vascular access failure. LMM increases the risk of VC and has the potential to predict vascular access failure.

Background: The EGFR (epidermal growth factor receptor) TKI (tyrosine kinase inhibitor) has become the standard treatment in lung cancer patients with EGFR mutations. When these patients are treated with EGFR TKI, 80~90% of the patients show responses to the drug. However the tumor begins to progress again following the development of resistance about 1 year later on average. About a half of resistance mechanisms are caused by the additional mutation of the EGFR gene (T790M), and the other half of the resistance mechanisms are caused by various mechanisms, with one of them being the overexpression of the AXL protein. Confirming AXL overexpression in circulating tumor cells (CTCs) can be an alternative method for tissue biopsy, but almost no research has been conducted on this so far. Here, we evaluate the AXL expression in CTC in case resistance occurs after the EGFR inhibitor treatment. Materials and Methods: The blood samples (10 ml) were collected from 10 EGFR TKI treated and relapsed lung cancer patients (TKI group) and 10 non-treated patients (control group). The blood samples were processed through Cytogen protocol to enrich CTCs. The enriched cells were immunofluorescent stained for CTC markers (EpCAM or Vimentin), AXL and WBC marker (CD45). The immunofluorescent stained cells were analyzed for each markers using Image Analysis program. Result: CTCs were detected by CTC markers in all patients from TKI group (range 0-210) and control group (range 1-42). AXL positive CTCs were detected in 9 out of 10 cases from TKI group and in all cases from control group. Interestingly, the quantification of AXL staining intensity in CTCs showed that AXL overexpression (3 fold or greater than baseline) was in 50% of TKI group and 20 % of control group. Conclusion: We have tested a new approach to evaluate the AXL overexpression in tumor cells of EGFR TKI resistant patients, and showed the feasibility of the this method. Most of lung cancer patients who undergo biopsy require hospitalization and some degree of complication due to biopsy is inevitable. Here we suggested that the blood-based method as a good alternative to the tissue biopsy in patients with tolerance. Citation Format: Young Hun Kim, Myoung Shin Kim, Jun Sup Lee, Hyun Kyung Lee, Jae Hyuk Lee, Young Woong Sohn, Koichi Tazaki, Kenji Nakamaru, Kenichi Wakita, Byung Hee Jeon, Seokhyung Kim, Se-Hoon Lee. Evaluation of AXL expression on circulating tumor cells from EGFR mutated lung cancer patients who have relapsed after the EGFR TKI treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1586.