The Profiling of Apoptosis-Associated MicroRNA Expressions of the Lung Adenocarcinoma.

OBJECTIVE: The most common histopathological subtype of lung cancer is adenocarcinoma. MicroRNAs are a class of non-coding RNAs that play roles in the regulation of gene expression. MicroRNAs affecting apoptosis may have different roles in lung adenocarcinoma development, progression, and differentiation. The objective of this study is to profile all known microRNAs linked to apoptosis in normal and lung cancer tissue using real-time polymerase chain reaction. MATERIAL AND METHODS: Tissues with adenocarcinoma and healthy tissues were taken from the same lung. The degree of differentiation of all tumors was determined. Expressions of 84 apoptosis-associated microRNAs in both tissues were analyzed by real-time polymerase chain reaction array. RESULTS: Eleven patients and 22 samples were included in the study. In the comparison of expression levels of apoptosis-associated microRNAs in normal and adenocarcinoma tissue, miR-134, miR-183-5p, miR-192-5p, miR-193b-3, miR-194-5p, miR-200c-3, miR212-3p, miR-25-3p, miR-449a, and miR-9-5p showed significant difference in downregulation. Receiver operating characteristic curve analysis of 10 identified microRNAs was performed, and cut-off values, sensitivity, and specificity were determined. No significant difference was found between microRNA expression levels in adenocarcinoma tissues classified as moderate-well to poorly differentiated. CONCLUSION: Differently, downregulated expressed apoptosis-associated microRNAs were detected in lung adenocarcinoma tissues. MicroRNAs can be used as biomarkers in the diagnosis in lung adenocarcinoma. The expression of microRNAs linked to apoptosis should be investigated in different lung cancer histological subtypes in order to identify potential biomarkers.

Comparative assessment of primary cancer cell culture techniques and cellular composition analysis in non-small cell lung cancer.

Preclinical models are required to study individual therapy responses to improve all cancer treatments, particularly non-small cell lung cancer (NSCLC). Patient-derived explants (PDEs) culture model is of great importance in terms of the possibility of tumor cell culture with the microenvironment, and the development of molecular mechanisms and personalized treatment methods. In our study, primary tumor culture with microenvironment was performed using different methods from tumor tissues obtained from 51 patients with NSCLC. To identify the most efficient method, mechanical, enzymatic, and tumor fluid techniques were applied. While the malignant cell rate was > 95% in 3 of these cases, the cancer-associated fibroblasts (CAF) microenvironment was high in 46 (80-94%) and low in 2 (1-79%). Subtyping of cells obtained from culture was performed using the light microscope and, if necessary, additional immunohistochemical markers. Consequently, using different techniques, here we successfully performed primary cell culture from patients with NSCLC with microenvironment. Depending on the cell type and culture conditions, proliferation rate was shown to be altered.

Capsaicin suppresses ciliary function, while inducing permeability in bronchial epithelial cell cultures of COPD patients.

Take Home Message: Capsaicin modified inflammatory response and caused toxicity in bronchial epithelial cultures from patients with COPD. More importantly, capsaicin decreased ciliary beat frequency and induced epithelial permeability and these effects were partially prevented by formoterol and roflumilast. Tear gas is widely used to halt mass demonstrations. Studies have reported its adverse effects on multiple organ systems; however, its effect on individuals with chronic respiratory diseases and the underlying mechanisms of these effects are unclear. For the first time in the literature, we investigated the effects of capsaicin, the active ingredient of tear gas, on bronchial epithelial cell (BEC) cultures obtained from well-characterized groups of nonsmokers, smokers, and patients with chronic obstructive pulmonary disease (COPD). BEC cultures were incubated with 50-500 µM capsaicin in the absence and presence of formoterol (1µM) and roflumilast (0.1 µM) for 24 h. Ciliary beat frequency (CBF) and transepithelial electrical resistance (TEER) were assessed at T1/4, T1/2, T1, T2, T4, T6, and T24 h, whereas the release of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-8, and lactate dehydrogenase (LDH) was measured at T24 h. Capsaicin (250 µM) significantly decreased CBF of all BEC cultures from T1/4 h to T24 h (p<0.05). Formoterol significantly prevented decreases in CBF induced by capsaicin. Higher concentrations of capsaicin (250-500 µM) significantly reduced TEER of BECs from nonsmokers (T2-T24 h), smokers (T24 h) and COPD patients (T2 and T24 h), which was partially prevented by roflumilast. Capsaicin (500 µM) decreased release of IL-8 (p<0.0001) and GM-CSF (p<0.05) while inducing release of LDH in BECs (p<0.05), and this was more prominent in BEC from patients with COPD. In conclusion, our findings demonstrate that capsaicin can suppress ciliary activity and cytokine release from BECs, induce BEC culture permeability and cellular toxicity and that these effects can be partially prevented by formoterol and roflumilast.