Introduction: Metformin is a drug of choice in the therapy of type II Diabetes mellitus. There is a growing evidence of metformin's antitumor activity, but the suggested mechanisms of such activity are still not fully elucidated. Aim: To investigate the effect of therapeutic doses of metformin on viability and mitochondrial status of human non-small cell lung carcinoma (NCI-H460) and human immortalized lung fibroblasts (MRC-5) cell lines. Material and methods: Acid phosphatase and Crystal Violet assays were used for the determination of NCI-H460 and MRC-5 cell viability after the treatment with metformin (10-60 µM) for 1-7 days. Mitochondrial membrane potential, production of reactive oxygen species and superoxide anion, as well as mitochondrial mass were measured using flow cytometry after the treatment of the cells for 3, 24 and 120 h, followed by staining with appropriate fluorochromes: JC-1, DHR, DHE and Mitotracker Red. Results: Metformin did not change the viability of both NCI-H460 and MRC-5 cells in all investigated time-points and all used concentrations. Depolarization of mitochondrial membrane was observed 3 h post-treatment in MRC-5 cells. Prolonged treatment (120 h) increased superoxide anion production and mitochondrial mass in NCI-H460 cells. No significant changes in production of reactive oxygen species were observed in both cells lines after short or extended exposure to metformin. Conclusion: : Therapeutic concentrations of metformin do not influence the viability of NCI-H460 and MRC-5 cells, but induce mitochondrial depolarization after short-term exposure in lung fibroblasts and increase production of superoxide anion and mitochondrial mass in lung carcinoma cells after prolonged treatment.

Out of the all newly diagnosed lung cancers, non-small cell lung carcinoma (NSCLC) comprises 80-85%. When treating advanced stages of the disease, conventional therapy shows poor results, which implies that there is a need for new drugs that will improve the response to current therapy. Metformin, drug used to threat Diabetes mellitus showed promising results in preclinical and retrospective clinical studies. We have analyzed prospective clinical trials investigating the combined effect of conventional therapy and metformin in treating lung cancer, as well as preclinical studies investigating its possible mechanisms of action published in PubMed database in the last 10 years. Several studies indicated that combination therapy with metformin led to the improvement in categories like overal survival (OS) and progression-free survival (PFS). However, the number of studies is limited and is characterized by a low number of subjects, as well as by a reduced compliance in subjects using metformin. Preclinical studies suggest cytotoxic effects of metformin, activation of apoptosis, as well as synergistic effect with chemotherapeutics, radiotherapy and biological agents used. The relevance of determined results is questionable, taking into account high metformin concentrations used in vitro. Based on the clinical studies published in the last ten years, there is insufficient data to conclude whether metformin improves prognostic factors in comparison to the conventional therapy. It is also not clear which mechanisms are responsible for possible beneficial effects of metformin. Future preclinical studies thus have to be better designed in order to increase their translational potential, while clinical studies have to be better controlled with improved selection and higher number of subjects enrolled.

Introduction: Cardiovascular diseases (CVD) represent the leading cause of morbidity and mortality (46 - 60%) among patients with chronic kidney disease (CKD). Three methods are used for kidney function replacement in patients with end-stage renal disease: hemodialysis, pertioneal dialysis and kidney transplantation. About 40% of the dialysis population develop coronary artery disease (CAD) due to chronic metabolic and inflammatory disorders. Risk factors for developing CAD in this group of patients include chronic anemia, secondary hyperparathyroidism, chronic inflammation, insulin resistance and volume overload. Aim: To determine the impact of metabolic and inflammatory disorders in developing CAD in patients with CKD that are chronically treated with hemodialysis. Material and methods: This case-control study included 115 patients with end-stage renal disease that were treated in Hemodialysis ward, Clinic for Nephrology, University Clinical Centre of Serbia. Data were collected for the period from January 2015 to December 2020. Elective coronarography was used to determine the presence and the characteristics of CAD. We also analyzed patient's laboratory findings, their demographic and clinical characteristics, as well as primary renal disease that led to the development of CKD in these patients. Additional parameters used in this study included the presence of Diabetes mellitus (DM) and duration of hemodialysis. Results: Coronary artery disease was diagnosed in 19 out of 115 patients (16.5%). Patients with CAD had a significantly higher levels of serum calcium (2.3 to 2.2 mmol/L) (p = 0.039), while other laboratory parameters did not show significant correlation. Most of the patients with CAD were male (16 of 19 patients, 84.3%, p = 0.01), while 31.6% (6 of 19 patients) with CAD were diagnosed with Diabetes mellitus (p = 0.009). Conclusion: The presence of Diabetes mellitus, higher calcium level, as well as male gender signicifantly increase the risk of developing CAD in patients chronically treated with hemodialysis.