Src family kinases as therapeutic targets in advanced solid tumors. What we have learned so far

Src is the prototypal member of Src Family tyrosine Kinases (SFKs), a large non-receptor kinase class that controls multiple signaling pathways in animal cells. SFKs activation is necessary for the mitogenic signal from many growth factors, but also for the acquisition of migratory and invasive phenotype. Indeed, oncogenic activation of SFKs has been demonstrated to play an important role in solid cancers; promoting tumor growth and formation of distant metastases. Several drugs targeting SFKs have been developed and tested in preclinical models and many of them have successfully reached clinical use in hematologic cancers. Although in solid tumors SFKs inhibitors have consistently confirmed their ability in blocking cancer cell progression in several experimental models; their utilization in clinical trials has unveiled unexpected complications against an effective utilization in patients. In this review, we summarize basic molecular mechanisms involving SFKs in cancer spreading and metastasization; and discuss preclinical and clinical data highlighting the main challenges for their future application as therapeutic targets in solid cancer progression

Tau oligomers accumulation sensitizes prostate cancer cells to docetaxel treatment

Purpose: Human tau is a highly dynamic, multifunctional protein expressed in different isoforms and conformers, known to modulate microtubule turnover. Tau oligomers are considered pathologic forms of the protein able to initiate specific protein accumulation diseases, called tauopathies. In our study, we investigated the potential association between autophagy and tau oligomers accumulation and its role in the response of prostate cancer cells to docetaxel. Methods: We evaluated in vitro the expression of tau oligomers in prostate cancer cell lines, PC3 and DU145, in presence of autophagy inhibitors and investigated the role of tau oligomers accumulation in resistance to docetaxel treatment. Results: Tau protein was basally expressed in prostate cancer lines as several monomeric and oligomeric forms. The pharmacologic inhibition of autophagy induced in cancer cells the accumulation of tau protein, with a prevalent expression of oligomeric forms. Immunofluorescence analysis of untreated cells revealed that tau was visible mainly in dividing cells where it was localized on the mitotic spindle. Inhibition of autophagy determined an evident upregulation of tau signal in dividing cells and the presence of aberrant monoastral mitotic spindles. The accumulation of tau oligomers was associated with DNA DSB and increased cytotoxic effect by docetaxel. Conclusions: Our data indicate that autophagy could exert a promoting role in cancer growth and during chemotherapy facilitating degradation of tau protein and thus blocking the antimitotic effect of accumulated tau oligomers. Thus, therapeutic strategies aimed at stimulating tau oligomers formation, such as autophagy inhibition, could be an effective adjuvant in cancer therapy

ITACA (ITalian ACcelerometric Archive): a Web Portal for the Dissemination of the Italian Strong Motion Data

The Italian strong-motion database contains 2182 three component waveforms generated by 1004 earthquakes with a maximum magnitude of 6.9 (1980 Irpinia earthquake) covering the period range from 1972 to 2004. The database is devoted to serving the seismological and engineering communities. The database can be accessed on-line at the site http://itaca.mi.ingv.it, where a wide range of search tools enables the user to interactively search events, recording stations and retrieve waveforms with particular characteristics, whose parameters can be specified, as needed, through a graphical user interface. A range of display options allows users to view data in different contexts, extract and download time series and spectral data. The database was created during a joint project between Istituto Nazionale di Geofisica e Vulcanologia (INGV, Italian institute for geophysics and vulcanology) and Dipartimento della Protezione Civile (DPC, Italian civil protection). The aim of the project was the collection, homogenization and distribution of data acquired over the time period 1972-2004 in Italy by different Italian institutions, namely Ente Nazionale per l’Energia Elettrica (ENEL, Italian electricity company), Ente per le Nuove tecnologie, l’Energia e l’Ambiente (ENEA, Italian energy and environment organization) and DPC. The project had multiple purposes, such as permanent strong motion monitoring and temporary monitoring during seismic sequences or before permanent installation. This database brings up to date the ENEA strong motion data collection which ended in 1993 and the European database where the most recent Italian data pertain to the Umbria-Marche sequence of 1997-1998 (Ambraseys at al., 2002). In addition effort was spent reviewing strong motion metadata and data processing to increase data quality and reliability. This article describes the steps that led to the completion of the project and provides an overview of the search capabilities available at the database interface website

The effect of quarantine due to Covid-19 pandemic on seizure frequency in 102 adult people with epilepsy from Apulia and Basilicata regions, Southern Italy

Objective: following the COVID-19 pandemic, a quarantine was imposed to all of regions Italy by 9th March until 3rd May 2020. We investigated the effect of COVID-19 infection and quarantine on seizure frequency in adult people with epilepsy (PwE) of Apulia and Basilicata regions, Southern Italy. Methods: This is an observational, retrospective study based on prospective data collection of 102 successive PWE. The frequency of seizures was evaluated during pre-quarantine (January- February), quarantine (March-April), and post-quarantine period (May-June), while PwE were divided into A) cases responding to treatment with ≤ 1 seizure per year; B) cases responding to treatment with 2-5 seizure per year; C) cases with drug-resistant epilepsy with ≤ 4 seizures per month; D) cases with drug-resistant epilepsy with 5-10 seizures per month. PwE underwent several self-report questionnaires regarding therapeutic compliance, mood, stress and sleep during quarantine period. Results: Approximately 50 % of PwE showed seizure frequency changes (22.55 % an increase and 27.45 % a reduction) during quarantine. Seizure frequency significantly (p < 0.05) increased in PwE responding to treatment with ≤ 1 seizure per year, while significantly (p < 0.05) reduced in PwE with drug-resistant epilepsy with 5-10 seizures per month. The data was not influenced by therapeutic adherence, sleep and depression. The analysis of anxiety showed a moderate level of anxiety in PwE responding to treatment with < 1 seizure per year, while moderate stress was perceived by all PwE. Seizure frequency changes were related to quarantine, but not to COVID-19 infection. In fact, unlike other regions of Italy, particularly Northern Italy, Apulia and Basilicata regions were less affected by COVID-19 infection, and almost all PwE recognized the quarantine as a stressful event. Emotional distress and anxiety due to social isolation, but also the relative reduction of triggers for epileptic seizures were the most important factors for changes in seizure frequency. Conclusions: Our study adds to the growing concern that the indirect effects of COVID-19 pandemic will far outstrip the direct consequences of the infection

Overview of the Italian strong Motion database ITACA 1.0

The Italian Strong Motion Database, ITACA, was developed within projects 2 S6 and S4, funded in the framework of the agreements between the Italian Department of 3 Civil Protection (Dipartimento della Protezione Civile, DPC) and the Istituto Nazionale di 4 Geofisica e Vulcanologia (INGV), starting from 2005. The alpha version of the database 5 was released in 2007 and subsequently upgraded to version 1.0 after: (i) including the most 6 recent strongmotion data (from2005 to 2007) recorded in Italy, in addition to the 2008 Parma 7 earthquake, M 5.4, and the M 4.0, 2009 Abruzzo seismic events; (ii) processing the raw 8 strong motion data using an updated procedure; (iii) increasing the number of stations with a 9 measured shear wave velocity profile; (iv) improving the utilities to retrieve time series and 10 ground motion parameters; (v) implementing a tool for selecting time series in agreement 11 with design-response spectra; (vi) compiling detailed station reports containing miscella12 neous information such as photo, maps and site parameters; (vii) developing procedures for 13 the automatic generation of station reports and for the updating of the header files. After such 14 improvements, ITACA 1.0 was published at the web site http://itaca.mi.ingv.it, in 2010. It 15 presently contains 3,955 three-component waveforms, comprising the most complete cata16 logue of the Italian accelerometric records in the period 1972–2007 (3,562 records) and the 17 strongest events in the period 2008–2009. Records were mainly acquired by DPC through its 18 Accelerometric National Network (RAN) and, in few cases, by local networks and temporary 19 stations or networks. This paper introduces the published version of the Italian StrongMotion 20 database (ITACA version 1.0) together with main improvements and new functionalities

Mapping litter decomposition by remote-detected indicators

Leaf litter decomposition is a key process for the functioning of natural ecosystems. An important limiting factor for this process is detritus availability, which we have estimated by remote sensed indices of canopy green biomass (NDVI). Here, we describe the use of multivariate geostatistical analysis to couple in situ measures with hyper-spectral and multi-spectral remote-sensed data for producing maps of litter decomposition. A direct relationship between the decomposition rates in four different CORINE habitats and NDVI, calculated at different scales from Landsat ETM+ multi-spectral data and MIVIS hyper-spectral data was found. Variogram analysis was used to evaluate the spatial properties of each single variable and their common interaction. Co-variogram and co-kriging analysis of the two variables turned out to be an effective approach for decomposition mapping from remote-sensed spatial explicit data

Bioactive potential of minor italian olive genotypes from apulia, sardinia and abruzzo

This research focuses on the exploration, recovery and valorization of some minor Italian olive cultivars, about which little information is currently available. Autochthonous and unexplored germplasm has the potential to face unforeseen changes and thus to improve the sustainability of the whole olive system. A pattern of nine minor genotypes cultivated in three Italian regions has been molecularly fingerprinted with 12 nuclear microsatellites (SSRs), that were able to unequivocally identify all genotypes. Moreover, some of the principal phenolic compounds were determined and quantified in monovarietal oils and the expression levels of related genes were also investigated at different fruit developmental stages. Genotypes differed to the greatest extent in the content of oleacein (3,4-DHPEA-EDA) and total phenols. Thereby, minor local genotypes, characterized by stable production and resilience in a low-input agro-system, can provide a remarkable contribution to the improvement of the Italian olive production chain and can become very profitable from a socio-economic point of view