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BackgroundOsteosarcoma (OS) is a highly aggressive bone cancer affecting children and young adults. Growing evidence connects the invasive potential of OS cells with their ability to form invadopodia (structures specialized in extracellular matrix proteolysis).ResultsIn this study, we tested the hypothesis that commonly used in vitro stimulators of mineralization limit the invadopodia formation in OS cells. Here we examined the invasive potential of human osteoblast-like cells (Saos-2) and osteolytic-like (143B) OS cells treated with the stimulators of mineralization (ascorbic acid and B-glycerophosphate) and observed a significant difference in response of the tested cells to the treatment. In contrast to 143B cells, osteoblast-like cells developed a mineralization phenotype that was accompanied by a decreased proliferation rate, prolongation of the cell cycle progression and apoptosis. On the other hand, stimulators of mineralization limited osteolytic-like OS cell invasiveness into collagen matrix. We are the first to evidence the ability of 143B cells to degrade extracellular matrix to be driven by invadopodia. Herein, we show that this ability of osteolytic-like cells in vitro is limited by stimulators of mineralization.ConclusionsOur study demonstrates that mineralization competency determines the invasive potential of cancer cells. A better understanding of the molecular mechanisms by which stimulators of mineralization regulate and execute invadopodia formation would reveal novel clinical targets for treating osteosarcoma.

Nibrin plays an important role in the DNA damage response (DDR) and DNA repair. DDR is a crucial signaling pathway in apoptosis and senescence. To verify whether truncated nibrin (p70), causing Nijmegen Breakage Syndrome (NBS), is involved in DDR and cell fate upon DNA damage, we used two (S4 and S3R) spontaneously immortalized T cell lines from NBS patients, with the founding mutation and a control cell line (L5). S4 and S3R cells have the same level of p70 nibrin, however p70 from S4 cells was able to form more complexes with ATM and BRCA1. Doxorubicin-induced DDR followed by cell senescence could only be observed in L5 and S4 cells, but not in the S3R ones. Furthermore the S3R cells only underwent cell death, but not senescence after doxorubicin treatment. In contrary to doxorubicin treatment, cells from all three cell lines were able to activate the DDR pathway after being exposed to γ-radiation. Downregulation of nibrin in normal human vascular smooth muscle cells (VSMCs) did not prevent the activation of DDR and induction of senescence. Our results indicate that a substantially reduced level of nibrin or its truncated p70 form is sufficient to induce DNA-damage dependent senescence in VSMCs and S4 cells, respectively. In doxorubicin-treated S3R cells DDR activation was severely impaired, thus preventing the induction of senescence.

AIMS: The objective of this study was to investigate inflammatory markers of the postpericardiotomy syndrome (PPS) and to determine individuals prone to develop the PPS. METHODS AND RESULTS: The study included 75 patients with a stable coronary disease that had underwent coronary artery bypass surgery. Serum samples were collected prior to the surgery and on the 5th day after the operation, to measure the concentration of IL-8, IL-6, IL-1β, IL-10, TNF, IL-12p70. All included patients were screened for the PPS before discharge from the hospital and 6 months after the surgery. The 49 patients developed the PPS (65.4%), among them 42 (56%) patients had pleural effusion, and 23 (31%) had pericardial effusion. The cytokine analysis has shown an inverse correlation between IL-8 concentration before the surgery, and the occurrence of the PPS (p = 0.026). There were also positive correlations between the magnitude of increase of IL-8 and IL-1β concentrations on the 5th day after the surgery and the occurrence of the PPS (p = 0.006 and p = 0.049 respectively). Multivariate analysis revealed IL-8 concentration before surgery as an independent risk factor of the PPS development (HR = 0.976; 95%CI: 0.956-0.996, p = 0.02). Cut-off point was established to assess the predictive value of IL-8 concentration (21.1 pg/ml). The test parameters were: sensitivity: 62.5%, specificity: 75%, positive predictive value: 83% and negative predictive value: 50%. Clinical evaluation showed the relationship between the hemoglobin concentration before the surgery and the PPS occurrence (p = 0.01). CONCLUSION: The IL-8 and IL-1β may participate in the postpericardiotomy syndrome pathogenesis, and the IL-8 concentration measurement may select patients with the risk of the PPS development.