Association between arachidonate lipoxygenase 15,c.-292 C > T gene polymorphism and non-cystic fibrosis bronchiectasis in children: a pilot study on the effects on airway lipoxin A4 and disease phenotype.

BACKGROUND: Persistent airway inflammation is a central feature of bronchiectasis. Arachidonate 15-lipoxygenase (ALOX-15) controls production of endogenous lipid mediators, including lipoxins that regulate airway inflammation. Mutations at various positions in ALOX-15 gene can influence airway disease development. We investigated association between ALOX-15,c.-292 C > T gene polymorphism and bronchiectasis unrelated to cystic fibrosis in Egyptian children. Also, lipoxin A4 (LXA4) level in bronchoalveolar lavage (BAL) was studied in relation to polymorphism genotypes and disease phenotypes determined by clinical, pulmonary functions, and radiological severity parameters. METHODS: This was an exploratory study that included 60 participants. Thirty children with non-cystic fibrosis bronchiectasis (NCFB) were compared with 30 age and sex-matched controls. ALOX-15,c.-292 C > T polymorphism was genotyped using TaqMan-based Real-time PCR. LXA4 was measured in BAL using ELISA method. RESULTS: There was no significant difference between patients and controls regarding ALOX-15,c.-292 C > T polymorphism genotypes and alleles (OR = 1.75; 95% CI (0.53-5.7), P = 0.35) (OR = 1; 95% CI (0.48-2), p = 1). BAL LXA4 level was significantly lower in patients, median (IQR) of 576.9 (147.6-1510) ng/ml compared to controls, median (IQR) of 1675 (536.8-2542) (p = 0.002). Patients with severe bronchiectasis had a significantly lower LXA4 level (p < 0.001). There were significant correlations with exacerbations frequency (r=-0.54, p = 0.002) and FEV1% predicted (r = 0.64, p = 0.001). Heterozygous CT genotype carriers showed higher LXA4 levels compared to other genotypes(p = 0.005). CONCLUSIONS: Low airway LXA4 in children with NCFB is associated with severe disease phenotype and lung function deterioration. CT genotype of ALOX-15,c.-292 C > T polymorphism might be a protective genetic factor against bronchiectasis development and/or progression due to enhanced LXA4 production.

Wild-Type Isocitrate Dehydrogenase 1 Over-Expression is Related to Cancer Stem Cells Survival in Lung Adenocarcinoma.

Altered metabolism is one of the characteristics of cancer cells. We evaluated the expression of wild-type Isocitrate Dehydrogenase 1 (IDH1) and the cancer stem cells (CSCs) marker CD44 by real-time PCR and levels of reduced form of glutathione in lung biopsies of 32 adenocarcinoma patients and 18 control subjects. We found that IDH1 and CD44 expression and the levels of reduced form of glutathione were significantly higher in lung adenocarcinoma patients. IDH1 was positively correlated with CD44 and reduced form of glutathione. In conclusion, wild-type IDH1 is over-expressed in lung adenocarcinoma which probably promoted tumor progression via increasing CSCs survival.

Prenatal Exposure to Endocrine Disruptors and Reprogramming of Adipogenesis: An Early-Life Risk Factor for Childhood Obesity.

Obesity is a global health problem. It is characterized by excess adipose tissue that results from either increase in the number of adipocytes or increase in adipocytes size. Adipocyte differentiation is a highly regulated process that involves the activation of several transcription factors culminating in the removal of adipocytes from the cell cycle and induction of highly specific proteins. Several other factors, including hormones, genes, and epigenetics, are among the most important triggers of the differentiation process. Although the main contributing factors to obesity are high caloric intake, a sedentary lifestyle, and genetic predisposition, strong evidence supports a role for life exposure to environmental pollutants. Endocrine-disrupting chemicals are exogenous, both natural and man-made, chemicals that disrupt the body signaling processes, thus interfering with the endocrine system. Several studies have shown that prenatal exposure to endocrine disruptors modulates the mechanisms, by which multipotent mesenchymal stem cells differentiate into adipocytes. This review discusses adipocytes differentiation and highlights the possible mechanisms of prenatal exposure to endocrine disruptors in reprogramming of adipogenesis and induction of obesity later in life. Therefore, this review provides knowledge that reduction of early life exposure to these chemicals could open the door for new strategies in the prevention of obesity, especially during childhood.

The diagnostic efficacy of nectin 4 expression in ovarian cancer patients.

CONTEXT: Nectin 4 plays a significant role in cancer cell growth and invasion. OBJECTIVE: To explore its diagnostic role in ovarian cancer. MATERIALS AND METHODS: Evaluation of nectin 4 expression in ovarian biopsies by real-time PCR and serum nectin 4 and CA-125 by ELISA in 39 ovarian cancer patients, 21 females with benign ovarian neoplasms and 25 control females. RESULTS: Nectin 4 expression was significantly higher in ovarian cancer patients and it was significantly correlated to serum nectin 4 and CA-125. CONCLUSIONS: Ovarian tissue expression and serum nectin 4 appear to be potential markers in ovarian cancer.

Evaluation of nestin in lung adenocarcinoma: relation to VEGF and Bcl-2.

CONTEXT: Nestin is a marker of multipotent precursor cells that is up regulated in cancer. OBJECTIVE: To explore its diagnostic role and its relationship to vascular endothelial growth factor (VEGF) and Bcl-2 in lung adenocarcinoma. MATERIALS AND METHODS: Evaluation of nestin expression in lung biopsies by real-time PCR and serum VEGF and Bcl-2 by ELISA in 27 adenocarcinoma patients and 15 control subjects. RESULTS: Nestin was significantly higher in lung adenocarcinoma patients especially with advanced grade and stage and it was significantly correlated to VEGF and Bcl-2. CONCLUSION: Nestin can be considered as a potential diagnostic marker in lung adenocarcinoma.