Background:Barrett’s oesophagus is a pre-malignant condition at gastroesophageal junction in which normal squamous epithelium is replaced by columnar shape epithelium, which predisposes oesophageal adenocarcinoma. It is known that Barrett’s oesophagus evolves as a consequence of chronic gastro-oesophageal reflux disease. Although progression of Barrett’s oesophagus to adenocarcinoma is still unclear, increasing incidence of oesophageal cancer and mortality worldwide make its study necessary. Several investigations have been made on the aetiology of oesophageal cancer. Most of them assessed genetical or environmental factors. However, potential role of bacteria in the development of oesophageal adenocarcinoma as a new environmental factor has not been addressed. Previous study on Barrett’s disease detected presence of Campylobacter concisus as a new emerging pathogen on Barrett’s and oesophageal cancer samples compared with healthy individuals. This indicates that this organism might involve in the progression of Barrett’s to oesophageal adenocarcinoma.Objectives:This study aimed to determine the effects of C. concisus on expression of three biomarkers including interleukin-18 (IL-18), tumour necrosis factor-α (TNF-α) and tumour suppressor gene (p53) in three Barrett's cell lines.Materials and Methods:Quantitative real-time PCR assays were developed to measure expression of pro-inflammatory mediators (IL-18 and TNF-α) and gene expression of p53 in Barrett's cell lines in co-culture with C. concisus.Results:The mentioned organism was able to modulate considerably expression of p53, TNF-α and IL-18 in a time-dependent manner.Conclusions:The results showed that microorganism influences expression of carcinogenesis biomarker and cytokines in cell line models and possibility promotes oesophageal adenocarcinoma.
Barrett's oesophagus (BO) is a complicated condition at the gastroesophageal junction in which normal squamous epithelium is changed to columnar and leads to oesophageal adenocarcinoma (OA). In the past decades, the prevalence of Barrett's disease and mortality rate of adenocarcinoma has significantly increased throughout the word. Data has shown that molecular pathogenesis of disease has not been clearly identified. However, a wide-range and successful administration of probiotics in cancer and gastrointestinal diseases has lead to the investigation into the possible inhibitory role of probiotics in oesophageal cancer. This study was conducted to evaluate the inhibitory effect of probiotics on the expression of biomarkers in an in vitro model. Two different Barrett's oesophageal cell lines were selected to co-culture with B. longum and Lactobacillus acidophilus to measure expression of IL-18, TNFa, p53 (tumour suppressor gene), cyclooxygenase 2 and CDX1 (caudal type homeobox 1) genes. In addition, two different aspects of probiotic administration, therapeutic and prophylactic test were also examined. Results showed that micro-organisms could inhibit expression of biomarkers and therapeutic culture conditions were more effective than prophylactic tests. The results obtained suggest that it is possible to incorporate the administration of probiotics in BO and OA prevention. INTRODUCTIONBarrett's oesophagus (BO) is well recognized as a precursor of oesophageal adenocarcinoma (OA), which is usually caused by gastroesophageal reflux disease (GORD). In BO, normal squamous epithelium is replaced by columnar intestinal epithelium because of GORD effects. It is known that progression of BO to OA includes sequence of metaplasia-dysplasia-adenocarcinoma, which is created by the effect of various factors and multiple pathways including environmental and genetic factors. The incidences of both Barrett's and oesophageal cancer have risen in the world particularly in the Western world and the UK by variation between 1/52 and 1/694, respectively (HvidJensen et al., 2011;Werner & Laßmann, 2012;Zimmerman, 2014). Subsequently, different studies have evaluated a range of putative factors that might support risk of progression of BO to OA. Current evidence suggests that progression of Barrett's disease is associated with the changes in bacterial population in GORD, BO and OA patients (Blackett et al., 2013). It has been suggested that Gram-negative bacteria (Lim & Fitzgerald, 2013;Sharma et al., 2013;Thrift et al., 2014). The use of probiotics has been established in the prevention of carcinogenic diseases. Probiotics are described as live micro-organisms applied in adequate amounts for beneficial use in order to strengthen the ordinary defence system and protect the gastrointestinal epithelium against pathogenic bacteria. Probiotics have been used successfully in cases of infant diarrhoea, food allergies, ulcerative colitis, colonic cancer, Crohn's disease and inflammatory bowel disease (Furrie et al., 2005;Steed et al., 2010;Ri...
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