In Stent Restenosis Predictors after Carotid Artery Stenting

Purpose. The long-term efficacy of carotid artery stenting is debated. Predictors of stent restenosis are not fully investigated. Our aim was to assess the incidence of long term restenosis after CAS and to identify some predictors of restenosis. Methods. We retrospectively selected 189 treated patients and we obtained the survival Kaplan-Meier curves for overall survival, for freedom from stroke or death and from restenosis. To correlate clinical, radiological, and procedural variables to stent restenosis, an univariate analysis was performed while to determine independent predictors of restenosis, a multivariate analysis was applied. Results. At 1, 3, and 5 years, the cumulative overall survival rate was 98%, 94%, and 92% with a cumulative primary patency rate of 87%, 82.5%, and 82.5%. The percentage residual stenosis after CAS and multiple stents deployment were independent predictors of restenosis, while diabetes and tumors are suggestive but not significant predictors of restenosis. Conclusions. In our CAS experience, encouraging long-term results seem to derive from both neurological event free rate and restenosis incidence. Adequate recanalization of the treated vessel is important to limit the development of stent restenosis. Multiple stents deployment, and with less evidence, diabetes, or neoplasms has to be considered to facilitate restenosis

Natural products from aquatic eukaryotic microorganisms for cancer therapy: Perspectives on anti-tumour properties of ciliate bioactive molecules

Several modern drugs, including those for cancer therapy, have been isolated from natural sources, are based on natural products and its derivatives, or mime natural products. Some of them are in clinical use, others in clinical trials. The success of natural products in drug discovery is related to their biochemical characteristics and to the technologic methods used to study their feature. Natural compounds may acts as chemo-preventive agents and as factors that increase therapeutic efficacy of existing drugs, thus overcoming cancer cell drug resistance that is the main factor determining the failure in conventional chemotherapy. Water environment, because of its physical and chemical conditions, shows an extraordinary collec- tion of natural biological substances with an extensive structural and functional diversity. The isolation of bioactive molecules has been reported from a great variety of aquatic organisms; however, the thera- peutic application of molecules from eukaryotic microorganisms remains inadequately investigated and underexploited on a systematic basis. Herein we describe the biological activities in mammalian cells of selected substances isolated from ciliates, free-living protozoa common almost everywhere there is water, focusing on their anti-tumour actions and their possible therapeutic activity. In particular, we unveil the cellular and molecular machine mediating the effects of cell type-specific signalling protein pheromone Er-1 and secondary metabolites, i.e. euplotin C and climacostol, in cancer cells. To support the feasibility of climacostol-based approaches, we also present novel findings and report additional mechanisms of action using both in vitro and in vivo models of mouse melanomas, with the scope of highlighting new frontiers that can be explored also in a therapeutic perspective. The high skeletal chemical difference of ciliate compounds, their sustainability and availability, also through the use of new organic synthesis/modifications processes, and the results obtained so far in biological studies provide a rationale to consider some of them a potential resource for the design of new anti-cancer drugs

Exposure to the Natural Compound Climacostol Induces Cell Damage and Oxidative Stress in the Fruit Fly <i>Drosophila melanogaster</i>

The ciliate Climacostomum virens produces the metabolite climacostol that displays antimicrobial activity and cytotoxicity on human and rodent tumor cells. Given its potential as a backbone in pharmacological studies, we used the fruit fly Drosophila melanogaster to evaluate how the xenobiotic climacostol affects biological systems in vivo at the organismal level. Food administration with climacostol demonstrated its harmful role during larvae developmental stages but not pupation. The midgut of eclosed larvae showed apoptosis and increased generation of reactive oxygen species (ROS), thus demonstrating gastrointestinal toxicity. Climacostol did not affect enteroendocrine cell proliferation, suggesting moderate damage that does not initiate the repairing program. The fact that climacostol increased brain ROS and inhibited the proliferation of neural cells revealed a systemic (neurotoxic) role of this harmful substance. In this line, we found lower expression of relevant antioxidant enzymes in the larvae and impaired mitochondrial activity. Adult offsprings presented no major alterations in survival and mobility, as well the absence of abnormal phenotypes. However, mitochondrial activity and oviposition behavior was somewhat affected, indicating the chronic toxicity of climacostol, which continues moderately until adult stages. These results revealed for the first time the detrimental role of ingested climacostol in a non-target multicellular organism