Towards In Vivo Imaging of Cancer Sialylation

In vivo assessment of tumor glucose catabolism by positron emission tomography (PET) has become a highly valued study in the medical management of cancer. Emerging technologies offer the potential to evaluate in vivo another aspect of cancer carbohydrate metabolism related to the increased anabolic use of monosaccharides like sialic acid (Sia). Sia is used for the synthesis of sialylated oligosaccharides in the cell surface that in cancer cells are overexpressed and positively associated to malignancy and worse prognosis because of their role in invasion and metastasis. This paper addresses the key points of the different strategies that have been developed to image Sia expression in vivo and the perspectives to translate it from the bench to the bedside where it would offer the clinician highly valued complementary information on cancer carbohydrate metabolism that is currently unavailable in vivo

EFFETTI CITOTOSSICI DEL PARTENOLIDE IN CELLULE DI CARCINOMA MAMMARIO UMANO MDA-MB231

Il carcinoma mammario triplo negativo è una forma di carcinoma mammario particolarmente aggressiva, a prognosi spesso infausta. Tale forma tumorale è resistente alle terapie tradizionalmente impiegate per il trattamento del carcinoma mammario, pertanto risulta strettamente necessario individuare una valida strategia terapeutica. In questa tesi viene valutato l’effetto del Partenolide (PN), un composto di origine naturale, sulle cellule di carcinoma mammario umano triplo negativo MDA-MB231. I risultati ottenuti evidenziano che il PN induce morte delle cellule MDA-MB231 mediante un meccanismo caspasi-indipendente, infatti l’inibitore generale delle caspasi z-VAD non è in grado di prevenire gli effetti citotossici del composto. Durante le prime ore di trattamento (1-3 h) il PN induce l’attivazione dell’enzima NADPH ossidasi con conseguente produzione di specie reattive dell’ossigeno (ROS). I ROS mediano diversi effetti indotti dal PN quali la deplezione dei gruppi tiolici e del GSH, l’attivazione di JNK e l’inibizione del fattore di trascrizione NF-kB. Durante questa fase il PN determina anche la comparsa di segni di autofagia, evidenziati dalla positività alla monodansilcadaverina e dall’incremento di noti marker autofagici quali LC3II e beclina-1. Prolungando il trattamento (16 h) lo stress ossidativo indotto dal PN determina una caduta del potenziale di membrana mitocondriale e la comparsa di segni di necrosi, evidenziata da un’elevata percentuale di cellule positive allo ioduro di propidio. In conclusione i dati ottenuti suggeriscono che il PN possa essere un ottimo candidato per il trattamento del carcinoma mammario triplo negativo

Superoxide Dismutase (SOD)-mimetic M40403 is protective in cell and fly models of paraquat toxicity: Implications for Parkinson disease

Parkinson disease is a debilitating and incurable neurodegenerative disorder affecting 3c1-2% of people over 65 years of age. Oxidative damage is considered to play a central role in the progression of Parkinson disease and strong evidence links chronic exposure to the pesticide paraquat with the incidence of the disease, most probably through the generation of oxidative damage. In this work, we demonstrated in human SH-SY5Y neuroblastoma cells the beneficial role of superoxide dismutase (SOD) enzymes against paraquat-induced toxicity, as well as the therapeutic potential of the SOD-mimetic compound M40403. Having verified the beneficial effects of superoxide dismutation in cells, we then evaluated the effects using Drosophila melanogaster as an in vivo model. Besides protecting against the oxidative damage induced by paraquat treatment, our data demonstrated that in Drosophila M40403 was able to compensate for the loss of endogenous SOD enzymes, acting both at a cytosolic and mitochondrial level. Because previous clinical trials have indicated that the M40403 molecule is well tolerated in humans, this study may have important implication for the treatment of Parkinson disease

KNOWLEDGE MANAGEMENT: THE PROPOSAL OF A THEORETICAL MODEL

The current organizations present a common feature: the knowledge is their most important asset and simultaneously, one of the trickiest to manage. The organizations do not always count with systematic ways to encode the possessed knowledge, which leads them to suffer with losses native from specialties and expertise from a personal level. Here we present the knowledge management, study field that purposes the formalization of the organizational knowledge. This paper intends to propose a knowledge management theoretical model to be used in profit and non profit making organizations. The paper was developed through a methodological approach using a theoretical proposition alongside literature review and theoretical discussion. With the obtained results, it was possible to realize that the presence of technological and non-technological mechanisms can aid the knowledge management. At the same time,the presence of facilitator and inhibitor factors impacts in the knowledge management practices, where these should be properly treated. Lastly, it was possible to observe several actions that might be fulfilled, so the effective knowledge management can happen

Reprint of: Proteomics in cardiovascular diseases::Unveiling sex and gender differences in the era of precision medicine

Cardiovascular diseases (CVDs) represent the most important cause of mortality in women and in men. Contrary to the long-standing notion that the effects of the major risk factors on CVD outcomes are the same in both sexes, recent evidence recognizes new, potentially independent, sex/gender-related risk factors for CVDs, and sex/gender-differences in the clinical presentation of CVDs have been demonstrated. Furthermore, some therapeutic options may not be equally effective and safe in men and women. In this context, proteomics offers an extremely useful and versatile analytical platform for biomedical researches that expand from the screening of early diagnostic and prognostic biomarkers to the investigation of the molecular mechanisms underlying CDVs. In this review, we summarized the current applications of proteomics in the cardiovascular field, with emphasis on sex and gender-related differences in CVDs

Erratum to "Double-blind Randomized Trial of tDCS Versus Sham in Parkinson Patients With Mild Cognitive Impairment Receiving Cognitive Training" Brain Stimulation 8 (2015) 1223-1225.

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Monitoring indoor temperatures of places of worship : a first step towards energy sustainability

This paper attempts to investigate the status quo of the indoor climate of some churches in Malta, ranging from large and small Baroque buildings to more contemporary buildings, during the winter season. This is carried out through an investigation of measured temperature and humidity, as a first step towards understanding and evaluating the extent of comfort issues in these buildings. It was found that the thermal mass of buildings plays a very important role in controlling indoor temperature in such free running structures. A contemporary church that was built of concrete showed extreme diurnal variations in indoor temperature during the winter season, which temperature was outside the comfort zone. On the other hand, Baroque churches had a relatively stable indoor temperature and they had fewer days where the temperature dropped below 18 °C.peer-reviewe

The oxygen radicals involved in the toxicity induced by parthenolide in MDA-MB-231 cells

It has been shown that the sesquiterpene lactone parthenolide lowers the viability of MDA-MB-231 breast cancer cells, in correlation with oxidative stress. The present report examined the different radical species produced during parthenolide treatment and their possible role in the toxicity caused by the drug. Time course experiments showed that in the first phase of treatment (0-8 h), and in particular in the first 3 h, parthenolide induced dichlorofluorescein (DCF) signal in a large percentage of cells, while dihydroethidium (DHE) signal was not stimulated. Since the effect on DCF signal was suppressed by apocynin and diphenyleneiodonium (DPI), two inhibitors of NADPH oxidase (NOX), we suggest that parthenolide rapidly stimulated NOX activity with production of superoxide anion (O2•-), which was converted by superoxide dismutase 1 (SOD1) into hydrogen peroxide (H2O2). In the second phase of treatment (8-16 h), parthenolide increased the number of positive cells to DHE signal. Since this event was not prevented by apocynin and DPI and was associated with positivity of cells to MitoSox Red, a fluorochrome used to detect mitochondrial production of O2•-, we suggest that parthenolide induced production of O2•- at the mitochondrial level independently by NOX activity in the second phase of treatment. Finally, in this phase, most cells became positive to hydroxyphenyl fluorescein (HPF) signal, a fluorescent probe to detect highly reactive oxygen species (hROS), such as hydroxyl radical and peroxynitrite. Therefore, parthenolide between 8-16 h of treatment induced generation of O2•- and hROS, in close correlation with a marked reduction in cell viability

Intra-abdominal desmoid tumors in familial adenomatous polyposis: How much do clinical and surgical variables interfere with their development?

Objective: Familial Adenomatous Polyposis is a complex hereditary disease that exposes the carrier to a great risk of Colorectal Cancer (CRC). After prophylactic surgery, intra-abdominal desmoid tumors are known to be one the most important cause of death. Therefore, recognition of increased-risk patients and modification of operative strategy may be crucial. Aim: The objective of this study was to estimate the desmoid tumor risk in relation to various surgical and clinical variables. Methods: Patients who had undergone polyposis since 1958 were included in the study. After exclusion criteria were met, those who had developed desmoid tumors were selected to undergo further evaluation. Results: The study revealed that the risk of developing desmoid tumors was associated with various factors such as sex ratio, colectomy, and reoperations. On the other hand, the type of surgery, family history, and surgical approach did not affect the risk of developing desmoid tumors. The data collected from 146 polyposis patients revealed that 16% had desmoid polyps. The sex ratio was 7:1, and the median age at colectomy was 28.6 years. Family history, multiple abdominal operations, and reoperations were some of the characteristics that were common in desmoid patients. Conclusion: Recognition of clinical (female sex) and surgical (timing of surgery and previous reoperations) data as unfavorable variables associated with greater risk may be useful during the decision-making process

Glomus Tumor of the Stomach: A Rare Cause of Upper Gastrointestinal Bleeding

Introduction. Glomus tumors (GTs) are benign neoplasm originating from the glomus body, commonly described in subungual region. The involvement abdominal is rare. Our aim is to describe a case of glomus tumor of the stomach that presented upper gastrointestinal bleeding. A 34-year-old woman was admitted with upper gastrointestinal bleeding and underwent an upper endoscopy that showed bleeding arising from an ulcerated lesion, treated by sclerosis therapy. A new endoscopy confirmed a submucosal lesion in upper portion of the stomach. During the laparotomy, a tumor at the upper anterior wall of gastric body was found and resected by a vertical gastrectomy. The pathological exam revealed hyperplastic smooth muscle fibers of the muscularis propria of the stomach wall, surrounded by hyaline stroma. The immunohistochemistry panel was positive for smooth muscle actin and type IV collagen, with low rate of mitosis studied by Ki-67 which allowed the final diagnosis of a gastric glomus tumor. Discussion. The majority of intraperitoneal glomus tumors occur in the stomach, and it is phenotypically similar to those localized in peripheral sites. Gastric GT generally is a benign tumor although it can be malignant and have the potential to metastasize. Conclusion. Even though gastric glomus tumor is rarely described, it should be considered as a possible cause of a major upper gastrointestinal bleeding