In orthopaedic and trauma surgery, implant-associated infections are increasingly treated with local application of antibiotics, which allows a high local drug concentration to be reached without eliciting systematic adverse effects. While ceftriaxone is a widely used antibiotic agent that has been shown to be effective against musculoskeletal infections, high local concentrations may harm the surrounding tissue. This study investigates the acute and subacute cytotoxicity of increasing ceftriaxone concentrations as well as their influence on the osteogenic differentiation of human bone progenitor cells. Human preosteoblasts were cultured in presence of different concentrations of ceftriaxone for up to 28 days and potential cytotoxic effects, cell death, metabolic activity, cell proliferation, and osteogenic differentiation were studied.Aims
Methods
In osteosarcoma, local control of the tumour is absolutely critical otherwise the chances of long term survival are <10% and may effectively approach zero. Radiotherapy is used in case of non-resectable tumours. Histone deacetylase inhibitors (HDACIs) can enhance the sensitivity of cells to photon radiation (XRT) by altering numerous molecular pathways. Therefore, we investigated the effect of the pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) on radiation response in osteosarcoma (OS) and rhabdomyosarcoma (RMS) cell lines. Clonogenic survival, cell cycle analysis, apoptosis and gammaH2AX phosphorylation as a marker of DNA double strand breaks (DSBs) were examined in two OS (KHOS-24OS, SAOS2) and two RMS (A-204, RD) cell lines treated with SAHA alone and SAHA plus XRT, respectively. Protein expression was investigated via immunoblot analysis, cell cycle analysis, measurement of apoptosis and gammaH2AX expression were performed using flow cytometry.Aim
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