Vitamin D deficiency negatively affects both the intestinal epithelial integrity and bone metabolism in children with Celiac disease

© 2020 Elsevier Masson SASBackground and aim: We aim to evaluate serum vitamin D levels, vitamin D receptor (VDR) expression in the intestinal epithelium, and their relation with epithelial barrier proteins and bone metabolism in children with Celiac disease (CD). Methods: Immunostaining for VDR, Claudin-2 and E-cadherin was performed in duodenal samples of the patients with CD and controls. H-score [∑Pi(I + 1)] where I is the intensity score and Pi is the corresponding percentage of stained cells was calculated for each samples. The clinic, laboratory and histopathological findings were compared between patients and controls. Results: Thirty-six patients with CD and age and sex matched 36 controls were enrolled. 25-OH vitamin D levels were significantly lower in the patient group compared to the control group. The mean bone mineral density (BMD) value was significantly lower in patients with vitamin D deficiency compared to patients with normal vitamin D level. H-scores for both VDR and Claudin-2 were significantly lower in patient group when compared to the control group. H-scores for VDR, Claudin-2 and E-cadherin were significantly lower in patients with vitamin D deficiency compared to patients with normal vitamin D level. There were positive correlations between 25-OH vitamin D level and H-scores for VDR, E-cadherin and Claudin-2 in patient group. Conclusions: Our findings showed that vitamin D deficiency is common among children with CD. Expression of VDR and epithelial barrier proteins Claudin-2 and E-cadherin which have important roles in paracellular pathway, was decreased in children with CD in correlation with histological findings of disease severity. Furthermore, deficiency of vitamin D was related to decreased expression of VDR and epithelial barrier proteins E-cadherin and Claudin-2. These findings indicate that paracellular pathway structures responsible for calcium absorption are disturbed in CD which is aggravated by vitamin D deficiency

Is second-line systemic chemotherapy beneficial in patients with non-small cell lung cancer (NSCLC)? A multicenter data evaluation by the Anatolian Society of Medical Oncology

Patients with advanced non-small cell lung cancer (NSCLC) generally require second-line treatment although their prognosis is poor. In this multicenter study, we aimed to detect the characteristics related to patients and disease that can predict the response to second-line treatments in advanced NSCLC. Data of 904 patients who have progressed after receiving first-line platinum-based chemotherapy in 11 centers with the diagnosis of stage IIIB and IV NSCLC and who were evaluated for second-line treatment were retrospectively analyzed. The role of different factors in determining the benefit of second-line treatment was analyzed. Median age of patients was 57 years (range 19-86). Docetaxel was the most commonly used (20.9 %, n = 189) single agent, while gemcitabine-platinum was the most commonly used (6.7 %, n = 61) combination chemotherapy regimen in second-line setting. According to survival analysis, median progression-free survival after first-line treatment (PFS2) was 3.5 months (standard error (SE) 0.2; 95 % confidence interval (CI), 3.2-3.9), median overall survival (OS) was 6.7 months (SE 0.3; 95 % CI, 6.0-7.3). In multivariate analysis, independent factors affecting PFS2 were found to be hemoglobin (Hb) level over 12 g/dl and treatment-free interval (TFI) longer than 3 months (p = 0.006 and 0.003, respectively). Similarly, in OS analysis, Hb level over 12 g/dl and time elapsed after the first-line treatment that is longer than 3 months were found to be independent prognostic factors (p = 0.0001 and 0.045, respectively). In light of these findings, determining and using the parameters for which the treatment will be beneficial prior to second-line treatment can increase success rate

Vascular endothelial growth factor antagonism restores epithelial barrier dysfunction via affecting zonula occludens proteins

Epithelial barrier dysfunction is important in the pathogenesis of asthma and allergic responses, and is therefore a therapeutic target. The aim of the present study was to investigate the effects of dexamethasone, a classic therapeutic agent, an anti-tumor necrosis factor agent (etanercept), which is used to treat difficult cases of asthma, and an anti-vascular endothelial growth factor (VEGF) agent (bevacizumab), which is an angiogenesis inhibitor, on zonula occludens (ZO) proteins in an experimental asthma model. The experimental model of asthma was developed using intraperitoneal (IP) and inhaled administration of ovalbumin in 38 BALB/c mice, which were divided into four groups. The control group (n=6) did not receive any treatment, while the four remaining groups (n=8 per group) received an IP injection of saline, etanercept, bevacizumab or dexamethasone, respectively. Occludin, claudin and junctional adhesion molecule (JAM) were immunohistochemically stained in the left middle lobe samples using an indirect avidin-peroxidase method, after which the staining was semiquantified with H-scores. Statistically significant differences were observed in the occludin, claudin and JAM H-scores among the four groups (P<0.001). In the untreated asthma, etanercept, bevacizumab and dexamethasone groups, the median H-scores for occludin were 93, 177, 280 and 198, respectively, while the H-scores for claudin were 82, 193.5, 274 and 202.5, respectively, and the median H-scores for JAM were 130, 210, 288 and 210, respectively. Pairwise comparisons revealed that all three ZO protein H-scores were significantly lower in the saline group when compared with each treatment group. However, the H-scores of the ZO proteins were not significantly different between the etanercept and dexamethasone groups. Furthermore, the bevacizumab group exhibited higher H-scores for all the proteins compared with the dexamethasone group. Therefore, antagonism of VEGF with bevacizumab restores the epithelial barrier to a greater extent when compared with dexamethasone treatment. This result may be promising for the development of novel therapeutic agents