No abstract

Gastrointestinal cancer represents one of the most diagnosed types of cancer. Cancer is a genetic and multifactorial disease, influenced by the host and environmental factors. It has been stated that 20% of cancer is caused by microorganisms such as Helicobacter pylori, hepatitis B and C virus, and human papillomavirus. In addition to these well-known microorganisms associated with cancer, it has been shown differences in the composition of the microbiota between healthy individuals and cancer patients. Some studies have suggested the existence of the selected microorganisms and their metabolites that can promote or inhibit tumorigenesis via some mechanisms. Recent findings have shown that gut microbiome and their metabolites can act as cancer promotors or inhibitors. It has been shown that gastrointestinal cancer can be caused by a dysregulation of the expression of non-coding RNA (ncRNA) through the gut microbiome. This review will summarize the latest reports regarding the relationship among gut microbiome, ncRNAs, and gastrointestinal cancer. The potential applications of diagnosing and cancer treatments will be discussed.

Background and Purpose: A critical role for sphingosine kinase/sphingosine-1phosphate (S1P) pathway in the control of airway function has been demonstrated in respiratory diseases. Here, we address S1P contribution in a mouse model of mild chronic obstructive pulmonary disease (COPD).Experimental Approach: C57BL/6J mice have been exposed to room air or cigarette smoke up to 11 months and killed at different time points. Functional and molecular studies have been performed.Key Results: Cigarette smoke caused emphysematous changes throughout the lung parenchyma coupled to a progressive collagen deposition in both peribronchiolar and peribronchial areas. The high and low airways showed an increased reactivity to cholinergic stimulation and α-smooth muscle actin overexpression. Similarly, an increase in airway reactivity and lung resistances following S1P challenge occurred in smoking mice. A high expression of S1P, Sph-K 2 , and S1P receptors (S1P 2 and S1P 3 ) has been detected in the lung of smoking mice. Sphingosine kinases inhibition reversed the increased cholinergic response in airways of smoking mice.Conclusions and Implications: S1P signalling up-regulation follows the disease progression in smoking mice and is involved in the development of airway hyperresponsiveness. Our study defines a therapeutic potential for S1P inhibitors in management of airways hyperresponsiveness associated to emphysema in smokers with both asthma and COPD.

Cigarette smoking is the leading risk factor for COPD and lung cancer establishment. Epidemiologically, COPD patients are 6.35 times more likely to develop lung cancer.To mimic COPD, we exposed mice to nose-only cigarette smoke and used human samples of lung adenocarcinoma patients according to the smoking and COPD status.Smoking C57Bl/6N mice had higher enlargement of alveoli, deposition of collagen and mucus production, associated to the release of IL-1-like cytokines, such as IL-1α and IL-1β at early time points and IL-18 at later time points. AIM2 expression was higher in lung recruited dendritic cells and macrophages in smoking mice, associated to the activation of caspase-11, rather than caspase-1. In support,129Sv mice, which are dysfunctional for caspase-11, had lower collagen deposition and mucus production, associated to lower release of IL-1-like and fibrotic TGFβ. Interestingly, higher expression of AIM2 in non-cancerous tissue of smoking COPD adenocarcinoma patients was correlated to a higher hazard ratio of poor survival rate than in patients who presented lower levels of AIM2.We found that AIM2 inflammasome is at the crossroad between COPD and lung cancer in that its higher presence is correlated to lower survival rate of smoking COPD adenocarcinoma patients.

No abstract