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San Fedele Superiore, Italy

Abdel-Haq H.,Istituto Superiore di Sanita
Journal of General Virology | Year: 2015

Development of numerous advanced techniques in recent years have allowed detection of the pathological prion protein (PrPTSE), the unique marker of transmissible spongiform encephalopathies (TSEs, or prion diseases), in the blood of animals and humans; however, an ante mortem screening test that can be used for the routine diagnosis of human prion diseases remains unavailable. A critical, analytical review of all the diagnostic assays developed to date will allow an evaluation of progress in this field and may facilitate the identification of the possible reasons for this delay. Thus, in this review, I provide a detailed overview of the techniques currently available for detecting PrPTSE and other markers of the disease in blood, as well as an analysis of the significance, feasibility, reliability and application spectrum for these methods. I highlight that factors intrinsic and extrinsic to blood may interfere with the detection of PrPTSE/prions, and that this is not yet taken into account in current tests. This may inspire researchers in this field to not only aspire to increase test sensitivity, but also to adopt other strategies in order to identify and overcome the limitations that hamper the development of a successful routine blood test for prion diseases. © 2015 The Author. Source

Rezza G.,Istituto Superiore di Sanita
BMC Public Health | Year: 2012

Dengue is a vector-borne disease that is estimated to affect millions of individuals each year in tropical and subtropical areas, and it is reemerging in areas that have been disease-free for relatively long periods of time. In this issue of the journal, Peng et al. report on a Dengue outbreak in a city in southern China that had been disease-free for more than two decades. The infection, which was due to serotype 1, was introduced by a traveler from South-east Asia and transmitted by Aedes albopictus, the Asian tiger mosquito. Compared to Aedes aegypti, which is the most important vector of Dengue, Ae albopictus is a less competent vector of arboviruses, and the epidemics it causes are milder. However, Ae albopictus is becoming an increasingly important vector because of its rapidly changing global distribution. In particular, the worldwide trade in second hand tires, which often contain water and are an ideal place for eggs and larvae, has been a key factor in the large-scale conquest of Ae albopictus, which easily adapts to new environments, even in a temperate climate. This expansion is creating new opportunities for viruses to circulate in new areas, becoming a common cause of epidemics in Ae aegypti-free countries, from Hawaii to Mauritius. The outbreak in China, like similar events, was mild and short-lived. Because epidemics due to Ae albopictus are milder, the replacement of Ae aegypti with the tiger mosquito could even result in public-health benefits. However, there is no solid evidence of this, and the milder course of the outbreak could be in part explained by the relatively short duration of the hot season in some affected areas. Since it is almost impossible to prevent Ae albopictus from being introduced in a country, mosquito-control measures at local level remain the most effective means of controlling arbovirus outbreaks. © 2012 Rezza; BioMed Central Ltd. Source

Di Paola L.,Biomedical University of Rome | Giuliani A.,Istituto Superiore di Sanita
Current Opinion in Structural Biology | Year: 2015

Protein molecules work as a whole, so that any local perturbation may resonate on the entire structure: allostery deals with this general property of protein molecules. It is worth noting a perturbation does not necessarily involve a conformational change but, more generally, it travels across the structure as an 'energy signal'. The atomic interactions within the network provide the structural support for this 'signaling highway'. Network descriptors, capturing network signaling efficiency, explain allostery in terms of signal transmission.In this review we will survey the key applications of graph theory to protein allostery. The complex network approach introduces a new perspective in biochemistry; as for applications, the development of new drugs relying on allosteric effects (allo-network drugs) represents a promising avenue of contact network formalism. © 2015 Elsevier Ltd. Source

Henssen A.,Istituto Superiore di Sanita
Oncotarget | Year: 2013

Medulloblastoma is the most common malignant brain tumor of childhood, and represents a significant clinical challenge in pediatric oncology, since overall survival currently remains under 70%. Patients with tumors overexpressing MYC or harboring a MYC oncogene amplification have an extremely poor prognosis. Pharmacologically inhibiting MYC expression may, thus, have clinical utility given its pathogenetic role in medulloblastoma. Recent studies using the selective small molecule BET inhibitor, JQ1, have identified BET bromodomain proteins, especially BRD4, as epigenetic regulatory factors for MYC and its targets. Targeting MYC expression by BET inhibition resulted in antitumoral effects in various cancers. Our aim here was to evaluate the efficacy of JQ1 against preclinical models for high-risk MYC-driven medulloblastoma. Treatment of medulloblastoma cell lines with JQ1 significantly reduced cell proliferation and preferentially induced apoptosis in cells expressing high levels of MYC. JQ1 treatment of medulloblastoma cell lines downregulated MYC expression and resulted in a transcriptional deregulation of MYC targets, and also significantly altered expression of genes involved in cell cycle progression and p53 signalling. JQ1 treatment prolonged the survival of mice harboring medulloblastoma xenografts and reduced the tumor burden in these mice. Our preclinical data provide evidence to pursue testing BET inhibitors, such as JQ1, as molecular targeted therapeutic options for patients with high-risk medulloblastomas overexpressing MYC or harboring MYC amplifications. Source

Mason Inc and Istituto Superiore Di Sanita | Date: 2014-09-04

Disclosed herein are: 1) methods for determining the appropriate drug therapy for a patient with colorectal cancer that has metastasized to the patients liver and/or lung; 2) methods for treating such a patient; and 3) pharmaceutical compositions for such treatment.

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