8 research outputs found
Synthetic Lethal Interaction with BCL-XL Blockade Deepens Response to Cetuximab in Patient-Derived Models of Metastatic Colorectal Cancer
LâOT nella prospettiva di unâanalisi costi-benefici sul settore spazio: i satelliti Cosmo-Skymed dellâASI
Nellâultimo decennio, un crescente numero di immagini satellitari ad alta risoluzione si Ăš reso accessibile per amministrazioni pubbliche, policymakers e scienziati, incrementando la quantitĂ e la qualitĂ di informazioni disponibili. Lâosservazione terrestre fornisce informazioni preziose sia al settore pubblico che a quello privato, consentendo di affrontare â al tempo stesso e con strumenti nuovi â sfide sociali globali come il cambiamento climatico e lâinquinamento dellâaria o applicazioni locali quali lâimplementazione di tecniche di agricoltura di precisione e monitoraggio delle infrastrutture urbane e di trasporto.
Il presente articolo si propone, attraverso lo studio della letteratura che utilizza dati di osservazione terrestre e unâanalisi bibliografica relativa a Cosmo SkyMed (CSM), di aprire la strada ad una efficace valutazione dellâimpatto socioeconomico dellâattivitĂ dellâAgenzia Spaziale Italiana (ASI) con riguardo alla creazione di prodotti e servizi innovativi generati dallâOsservazione Terrestre. Buona parte dei benefici legati alla disponibilitĂ di dati di osservazione della terra restano potenziali, inespressi e sottovalutati. La presente analisi prevede lâidentificazione delle barriere organizzative e istituzionali che limitano il pieno sfruttamento delle informazioni da dati OT, cosĂŹ come la formulazione di solide raccomandazioni di policy al fine di valorizzare il settore downstream spaziale italiano, soprattutto in materia di economia pubblica e fiscal compliance (e.g. accertamento degli abusivismi edilizi)
Accounting for the impact of space policies: The case of the Italian Space Agency
The purpose of this work is assessing the impact of the Italian Space Agency (ASI) on the performance of the Italian space stakeholders through three specific policies, i.e. public procurement, public investment in Earth observation, and collaboration with the scientific community. This article explores multiple surveys targeting upstream and downstream companies, universities, and research centres in the space economy to estimates the cost-benefit ratio. We find that the socio-economic benefit of ASI policies is positive and, when considering upstream companies and downstream intermediate users in the field of Earth observation (EO), the impact is particularly high in the EO sector. The surveys show evidence of a positive effect of public procurement and EO data on the Italian space economy, both in terms of innovation and economic performance. Finally, we observe a significant impact of ASI also on the scientific community
INKA, an integrative data analysis pipeline for phosphoproteomic inference of active kinases
Abstract Identifying hyperactive kinases in cancer is crucial for individualized treatment with specific inhibitors. Kinase activity can be discerned from global protein phosphorylation profiles obtained with mass spectrometryâbased phosphoproteomics. A major challenge is to relate such profiles to specific hyperactive kinases fueling growth/progression of individual tumors. Hitherto, the focus has been on phosphorylation of either kinases or their substrates. Here, we combined labelâfree kinaseâcentric and substrateâcentric information in an Integrative Inferred Kinase Activity (INKA) analysis. This multipronged, stringent analysis enables ranking of kinase activity and visualization of kinaseâsubstrate networks in a single biological sample. To demonstrate utility, we analyzed (i) cancer cell lines with known oncogenes, (ii) cell lines in a differential setting (wildâtype versus mutant, +/â drug), (iii) preâ and onâtreatment tumor needle biopsies, (iv) cancer cell panel with available drug sensitivity data, and (v) patientâderived tumor xenografts with INKAâguided drug selection and testing. These analyses show superior performance of INKA over its components and substrateâbased singleâsample tool KARP, and underscore target potential of highâranking kinases, encouraging further exploration of INKA's functional and clinical value
INKA, an integrative data analysis pipeline for phosphoproteomic inference of active kinases
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Phosphoproteomics of patient-derived xenografts identifies targets and markers associated with sensitivity and resistance to EGFR blockade in colorectal cancer
Epidermal growth factor receptor (EGFR) is a well-exploited therapeutic target in metastatic colorectal cancer (mCRC). Unfortunately, not all patients benefit from current EGFR inhibitors. Mass spectrometry-based proteomics and phosphoproteomics were performed on 30 genomically and pharmacologically characterized mCRC patient-derived xenografts (PDXs) to investigate the molecular basis of response to EGFR blockade and identify alternative drug targets to overcome resistance. Both the tyrosine and global phosphoproteome as well as the proteome harbored distinctive response signatures. We found that increased pathway activity related to mitogen-activated protein kinase (MAPK) inhibition and abundant tyrosine phosphorylation of cell junction proteins, such as CXADR and CLDN1/3, in sensitive tumors, whereas epithelial-mesenchymal transition and increased MAPK and AKT signaling were more prevalent in resistant tumors. Furthermore, the ranking of kinase activities in single samples confirmed the driver activity of ERBB2, EGFR, and MET in cetuximab-resistant tumors. This analysis also revealed high kinase activity of several members of the Src and ephrin kinase family in 2 CRC PDX models with genomically unexplained resistance. Inhibition of these hyperactive kinases, alone or in combination with cetuximab, resulted in growth inhibition of ex vivo PDX-derived organoids and in vivo PDXs. Together, these findings highlight the potential value of phosphoproteomics to improve our understanding of anti-EGFR treatment and response prediction in mCRC and bring to the forefront alternative drug targets in cetuximab-resistant tumors.</p