Search

Head and neck squamous cell carcinomas (HNSCC) are a diverse group of tumors with high morbidity and mortality that have remained mostly unchanged over the past decades. The epidermal growth factor receptor (EGFR) is often overexpressed and activated in these tumors and strongly contributes to their pathogenesis. Still, EGFR-targeted therapies such as monoclonal antibodies and kinase inhibitors have demonstrated only limited improvements in the clinical outcome of this disease. Here, we take advantage of the extraordinary affinity of EGF for its cognate receptor to specifically target magnetite-containing nanoparticles to HNSCC cells and mediate, in vitro , their cellular upload. On the basis of this, we show efficient accumulation, in vivo , of such nanoparticles in subcutaneous xenograft tumor tissues in sufficient amounts to be able to mediate visualization by magnetic resonance imaging. Overall, our EGF-coated nanosystem may warrant, in the near future, novel and very efficient theranostic approaches to HNSCC., Competing Interests: The authors declare no competing financial interest.

Auranofin is a gold based drug in clinical use since 1985 for the treatment of rheumatoid arthritis. Beyond its antinflammatory properties, auranofin exhibits other attractive biological and pharmacological actions such as a potent in vitro cytotoxicity and relevant antimicrobial and antiparasitic effects that make it amenable for new therapeutic indications. For instance, auranofin is currently tested as an anticancer agent in four independent clinical trials; yet, its mode of action is highly controversial. With the present study, we explore the effects of auranofin in Saccharomyces cerevisiae and its likely mechanism. Notably, auranofin is reported to induce remarkable yeast growth inhibition. Solid evidence is provided that growth inhibition is the consequence of a direct cytotoxic insult occurring at the mitochondrial level; a profound depression of cell respiration is indeed clearly documented as the main cause of cell death while induction of ROS plays only a secondary role. More in detail, the mitochondrial NADH kinase Pos5 is identified as a primary target for auranofin. The implications of these results are discussed in the frame of current mechanistic knowledge on the cellular effects of auranofin and of its role as a prospective anticancer drug., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The prognosis of colorectal cancer depends on the stage of the disease. However, even within the same stage there may be different outcomes in terms of recurrence and survival. Therefore, it is clear that as well as pathological stage, novel biomarkers that are capable of improving risk stratification and therapeutic decision-making are required. The present study aimed to evaluate the potential roles of two previously proposed biomarkers of tumour status: B-cell lymphoma 2 (Bcl-2) and β-catenin. A total of 412 patients undergoing surgery for primary colorectal cancer were studied. Tumour specimens of the patients were collected, fixed and processed for immunohistochemical detection of Bcl-2 and β-catenin. The data were then analyzed in relation to disease-free survival and overall survival. Pathological stage was the only variable that was significantly correlated with both disease-free and overall survival. The expression levels of neither Bcl-2 nor β-catenin were able to accurately predict prognosis. However, there was a clear association between nuclear β-catenin expression levels and disease-free survival in the three tumour stages. There was an increased hazard ratio in stage I and II nuclear β-catenin positive tumours, whereas there was a marked decrease in risk in stage III positive tumours. A similar effect was also observed with regards to overall survival, however this finding was not significant. The results of the present study suggest that conventional pathological tumour staging is the only accurate prognostic method. Neither Bcl-2 or β-catenin were shown to be useful biomarkers for the prognosis of colorectal cancer. However, the heterogeneous behaviour of nuclear β-catenin expression in the various tumour stages may indicate a possible role in predicting the response of patients to chemotherapy. Therefore, nuclear β-catenin expression may be a biomarker for the prediction of improved responses to chemotherapy.

We used X-rays from a linear accelerator and from a low energy therapeutic source to calibrate the single cell gel electrophoresis (comet assay), a widely used method to measure DNA damage. Gamma-rays from 60Co, with known efficiency in inducing DNA breakage, were used as reference. Human lymphocytes and one murine tumour cell line, F10-M3 cells, were irradiated under different experimental conditions. A similar relationship between radiation dose and induced DNA damage was obtained with gamma- and X-rays. A calibration curve was constructed to convert the comet assay raw data into break frequency. The median levels of DNA breaks and oxidative damage in circulating lymphocytes from healthy volunteers were calculated to be 0.76 and 0.80 breaks/10(9) Da, respectively, (0.50 and 0.52 breaks/10(6) bp). The values of oxidative DNA damage were in the same order of magnitude as those found by others with HPLC methods.