Ecotoxicological effects of ciprofloxacin on freshwater species: data integration and derivation of toxicity thresholds for risk assessment

Although antibiotics have been increasingly used and detected in natural samples, their ecotoxicological effects on aquatic wildlife are not yet extensively studied. Considering the environmental threat posed by the biological activity of antibiotics it is quite relevant to assess the resulting impact, especially on sub-lethal endpoints. As such, this study evaluated the effects of ciprofloxacin on Pseudokirchneriella subcapitata and Lemna minor growth, on the survival and reproduction of Daphnia magna and on Gambusia holbrooki survival. The risks associated with ciprofloxacin effects on non-target organisms were quantified through the calculation of the PEC/PNEC ratio. Overall, the toxicity values obtained (at the mg L(-1) level) were higher than the environmental concentrations. P. subcapitata and L. minor were more sensitive under short-term exposures than D. magna and G. holbrooki. No acute toxicity was observed for fish. The chronic assay with D. magna evidenced that long term exposures to lower concentrations of this antibiotic induced impairments on its life-history parameters. Such outcome may pre-empt potential damages on the long-term maintenance of natural populations continuously exposed to the input of antibiotics. Indeed, the PEC/PNEC ratios showed that ciprofloxacin represents a risk for the most sensitive aquatic organisms, since the defined threshold of an acceptable risk was considerably surpassed.publishe

Targeted therapies in bladder cancer: an overview of in vivo research

Survival of patients with muscle-invasive bladder cancer is poor and new therapies are needed. Currently, none of the targeted agents that are approved for cancer therapy have been approved for the treatment of bladder cancer and the few clinical trials that have been performed had limited success, often owing to a lack of efficacy and toxic effects. However, many other novel targeted agents have been investigated in animal models of bladder cancer. EGFR, FGFR-3, VEGF, mTOR, STAT3, the androgen receptor and CD24 are molecular targets that could be efficiently inhibited, resulting in reduced tumour growth, and that have been investigated in multiple independent studies. Several other targets, for example COX-2, IL-12, Bcl-xL, livin and choline kinase a, have also been observed to inhibit tumour growth, but these findings have not been replicated to date. Limitations of several studies include the use of cell lines with mutations downstream of the target, providing resistance to the tested therapy. Furthermore, certain technologies, such as interfering RNAs, although effective in vitro, are not yet ready for clinical applications. Further preclinical research is needed to discover and evaluate other possible targets, but several validated targets are now available to be studied in clinical trials