The history of small extracellular vesicles and their implication in cancer drug resistance

Small extracellular vesicles (EVs) in the last 20 years are demonstrated to possess promising properties as potential new drug delivery systems, biomarkers, and therapeutic targets. Moreover, EVs are described to be involved in the most important steps of tumor development and progression including drug resistance. The acquired or intrinsic capacity of cancer cells to resist chemotherapies is one of the greatest obstacles to overcome to improve the prognosis of many patients. EVs are involved in this mechanism by exporting the drugs outside the cells and transferring the drug efflux pumps and miRNAs in recipient cells, in turn inducing drug resistance. In this mini-review, the main mechanisms by which EVs are involved in drug resistance are described, giving a rapid and clear overview of the field to the readers

Composizione e attività biologica di “idrolati” di agrumi

Gli idrolati, o acque aromatiche, sono prodotti naturali ricavati dalla distillazione di piante o parti di piante fresche che conservano intatte le loro proprietà e possono essere utilizzati a diverso scopo1. Essi sono comunemente considerati un sottoprodotto degli oli essenziali, ma in realtà, data la diversa composizione e la conseguente maggiore delicatezza, hanno un loro apprezzabile utilizzo, legato comunque al mantenimento delle proprietà delle piante da cui derivano. Nell’industria agrumaria gli idrolati sono il risultato della produzione degli oli essenziali attraverso spremitura a freddo delle bucce degli agrumi e sono considerati un rifiuto da smaltire. Lo studio della composizione chimica dell’idrolato è poco noto: gli idrolati sono comunque ricchi di composti prevalentemente ossigenati che oltre a conferire un gradevole profumo, possono donargli numerose proprietà biologiche. Abbiamo quindi deciso di intraprenderne uno studio di caratterizzazione LC-MS e GC-MS sull’idrolato dell’arancia di Ribera per identificare sostanze di interesse farmaceutico, cosmetico, ecc. e di possibile attività biologica. Questo potrebbe rappresentare per l’industria agrumaria un valore aggiunto nel valorizzare un prodotto attualmente di scarto. I risultati biologici preliminari hanno indicato che l’estratto organico inibisce la crescita di forme planctoniche di S. Aureus ATCC 25923 ad una concentrazione 5 mg/mL. Sono in corso ulteriori studi per valutare l’attività contro ceppi Gram-negativi e di inibizione di biofilm di Gram-positivi e Gram-negativi. Bibliografia 1 Lante, A.; Tinello, F. Innovative Food Science and Emerging Technologies, 2015, 27, 154–15

DNA nanotechnology for cancer therapy

DNA nanotechnology is an emerging and exciting field, and represents a forefront frontier for the biomedical field. The specificity of the interactions between complementary base pairs makes DNA an incredible building material for programmable and very versatile two- and three-dimensional nanostructures called DNA origami. Here, we analyze the DNA origami and DNA-based nanostructures as a drug delivery system. Besides their physical-chemical nature, we dissect the critical factors such as stability, loading capability, release and immunocompatibility, which mainly limit in vivo applications. Special attention was dedicated to highlighting the boundaries to be overcome to bring DNA nanostructures closer to the bedside of patients

Il fenomeno delle dipendenze patologiche nella Provincia di Ragusa. Anno 2005. I Rapporto

Report on the state of legal and illegal substances use in the territory of Ragusa ProvinceIl Report analizza il fenomeno delle dipendenze nel territorio della Provincia di Ragusa. La descrizione del fenomeno si sviluppa intorno all\u27analisi degli indicatori individuati dall\u27Osservatorio Europeo delle Dipendenze di Lisbona (OEDT): 1-uso di sostanze nella popolazione generale (questo indicatore va a rilevare i comportamenti nei confronti di alcol e sostanze psicoattive da parte della popolazione generale); 2-prevalenza d\u27uso problematico delle sostanze psicoattive; 3-domanda di trattamento degli utilizzatori di sostanze; 4-mortalit? degli utilizzatori di sostanze; 5-malattie infettive. Altri due importanti indicatori che si stanno sviluppando, e che vengono qui illustrati, sono l\u27analisi delle Schede di Dimissione Ospedaliera (SDO) e gli indicatori relativi alle conseguenza sociali dell\u27uso di droghe (criminalit? droga correlata). Inoltre sono state applicate diverse metodologie standard di stima sia per quantificare la quota parte sconosciuta di utilizzatori di sostanze che non afferiscono ai servizi, sia per identificarne alcune caratteristiche

Impact of gastrointestinal side effects on patients’ reported quality of life trajectories after radiotherapy for prostate cancer: Data from the prospective, observational pros-it CNR study

Radiotherapy (RT) represents an important therapeutic option for the treatment of localized prostate cancer. The aim of the current study is to examine trajectories in patients’ reported quality of life (QoL) aspects related to bowel function and bother, considering data from the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study, analyzed with growth mixture models. Data for patients who underwent RT, either associated or not associated with androgen deprivation therapy, were considered. QoL outcomes were assessed over a 2-year period from the diagnosis, using the Italian version of the University of California Los Angeles-Prostate Cancer Index (Italian-UCLA-PCI). Three trajectories were identified for the bowel function; having three or more comorbidities and the use of 3D-CRT technique for RT were associated with the worst trajectory (OR = 3.80, 95% CI 2.04–7.08; OR = 2.17, 95% CI 1.22–3.87, respectively). Two trajectories were identified for the bowel bother scores; diabetes and the non-Image guided RT method were associated with being in the worst bowel bother trajectory group (OR = 1.69, 95% CI 1.06–2.67; OR = 2.57, 95% CI 1.70–3.86, respectively). The findings from this study suggest that the absence of comorbidities and the use of intensity modulated RT techniques with image guidance are related with a better tolerance to RT in terms of bowel side effects

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study

Background: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care

Engineered DNA nanostructures for targeted breast cancer therapy

In this work, I am presenting my PhD project accomplished during three years in nanotechnology. In this dissertation, we address the challenge of developing a drug delivery system based on DNA nanotechnology effective at preclinical stage on breast cancer (BC). In the last decades, DNA has drawn attention of many research groups as a smart nanomaterial. High stability, easy custom synthesis, mechanical rigidity and high loading efficiency are strong suitable properties of DNA to setup a drug delivery system. Unfortunately, the application of DNA nanotechnology in vivo is limited. Once in the bloodstream, DNA is fastly recognized as exogenous material by the immune system and DNAse that favors its rapid degradation. To answer this challenge, we developed a new DDS based on short tube DNA origami (STDO) of 30 nm in length, precisely designed to fit inside pegylated liposomes (LSTDO). This hybrid system combines the properties of stealth liposome to freely circulate in the blood stream and DNA origami to interact with doxorubicin, an anthracycline utilized in the treatment of BC. In vitro and in vivo antitumor efficacy of LSTDOdoxo was assessed showing an effective improvement of the therapeutic index of doxorubicin. In particular, the LSTDOdoxo accumulates in the tumor taking advantage from the EPR effect and reduces the tumor burden. It was also demonstrated that the encapsulation of DNA origami inside pegylated liposomes allowed us to develop a safe drug delivery system, which avoid the immune response induced by the administration of exogenous DNA

An Effective Multi-Stage Liposomal DNA Origami Nanosystem for In Vivo Cancer Therapy

DNA origami systems could be important candidates for clinical applications. Unfortunately, their intrinsic properties such as the activation of non-specific immune system responses leading to inflammation, instability in physiological solutions, and a short in vivo lifetime are the major challenges for real world applications. A compact short tube DNA origami (STDO) of 30 nm in length and 10 nm in width was designed to fit inside the core of a stealth liposome (LSTDO) of about 150 nm to remote load doxorubicin. Biocompatibility was tested in three-dimensional (3D) organoid cultures and in vivo. Efficacy was evaluated in different cell lines and in a xenograft breast cancer mouse model. As described in a previous work, LSTDO is highly stable and biocompatible, escaping the recognition of the immune system. Here we show that LSTDO have an increased toleration in mouse liver organoids used as an ex vivo model that recapitulate the tissue of origin. This innovative drug delivery system (DDS) improves the antitumoral efficacy and biodistribution of doxorubicin in tumor-bearing mice and decreases bone marrow toxicity. Our application is an attractive system for the remote loading of other drugs able to interact with DNA for the preparation of liposomal formulations

Simbolicità e emotività negli animali non umani: un tema attuale con radici lontane

Are the communication systems of non-human animals endowed with the property of symbolism or are they merely expressions of emotional states? The question has pervaded the philosophical debate at least since the time of Descartes and is now abundantly discussed in the field of cognitive ethology. In this paper, the topic is summarized both from the philosophical point of view (reconsidering Brentan’s notion of 'intentionality', often referred to by ethologists, too) and from the experimental point of view, referring to some well-known case-studies of the last decades. It is suggested that a dichotomous, all-or-nothing, vision of the relationship between symbolism and emotionality is, today, outdated in both conceptual and methodological terms. Available evidence on the communication of different primate species shows that the two components interact closely. An embodied approach to animal communication seems to represent an effective way out also from a theoretical point of view