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- Balossino, I., et al.
(author)
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U-Rania : A neutron detector based on μ-rwell technology
- 2020
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In: Journal of Instrumentation. - 1748-0221. ; 15:9
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Journal article (peer-reviewed)abstract
- In the framework of the ATTRACT-uRANIA project, funded by the European Community, we are developing an innovative neutron imaging detector based on micro-Resistive WELL (μ-RWELL) technology. The μ-RWELL, based on the resistive detector concept, ensuring an efficient spark quenching mechanism, is a highly reliable device. It is composed by two main elements: A readout-PCB and a cathode. The amplification stage for this device is embedded in the readout board through a resistive layer realized by means of an industrial process with DLC (Diamond-Like Carbon). A thin layer of \boro on the copper surface of the catode allows the thermal neutrons detection through the release of \litio and α particles in the active volume. This technology has been developed to be an efficient and convenient alternative to the 3He shortage. The goal of the project is to prove the feasibility of such a novel neutron detector by developing and testing small planar prototypes with readout boards suitably segmented with strip or pad readout, equipped with existing electronics or readout in current mode. Preliminary results from the test with different prototypes, showing a good agreement with the simulation, will be presented together with construction details of the prototypes and the future steps of the project.
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- Firuzi, O, et al.
(author)
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Role of c-MET Inhibitors in Overcoming Drug Resistance in Spheroid Models of Primary Human Pancreatic Cancer and Stellate Cells
- 2019
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In: Cancers. - : MDPI AG. - 2072-6694. ; 11:5
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Journal article (peer-reviewed)abstract
- Pancreatic stellate cells (PSCs) are a key component of tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) and contribute to drug resistance. c-MET receptor tyrosine kinase activation plays an important role in tumorigenesis in different cancers including PDAC. In this study, effects of PSC conditioned medium (PCM) on c-MET phosphorylation (by immunocytochemistry enzyme-linked immunosorbent assay (ELISA)) and drug response (by sulforhodamine B assay) were investigated in five primary PDAC cells. In novel 3D-spheroid co-cultures of cyan fluorescence protein (CFP)-firefly luciferase (Fluc)-expressing primary human PDAC cells and green fluorescence protein (GFP)-expressing immortalized PSCs, PDAC cell growth and chemosensitivity were examined by luciferase assay, while spheroids’ architecture was evaluated by confocal microscopy. The highest phospho-c-MET expression was detected in PDAC5 and its subclone sorted for “stage specific embryonic antigen-4” (PDAC5 (SSEA4)). PCM of cells pre-incubated with PDAC conditioned medium, containing increased hepatocyte growth factor (HGF) levels, made PDAC cells significantly more resistant to gemcitabine, but not to c-MET inhibitors. Hetero-spheroids containing both PSCs and PDAC5 (SSEA4) cells were more resistant to gemcitabine compared to PDAC5 (SSEA4) homo-spheroids. However, c-MET inhibitors (tivantinib, PHA-665752 and crizotinib) were equally effective in both spheroid models. Experiments with primary human PSCs confirmed the main findings. In conclusion, we developed spheroid models to evaluate PSC–PDAC reciprocal interaction, unraveling c-MET inhibition as an important therapeutic option against drug resistant PDAC.
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- Kidiyoor, GR, et al.
(author)
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ATR is essential for preservation of cell mechanics and nuclear integrity during interstitial migration
- 2020
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4828-
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Journal article (peer-reviewed)abstract
- ATR responds to mechanical stress at the nuclear envelope and mediates envelope-associated repair of aberrant topological DNA states. By combining microscopy, electron microscopic analysis, biophysical and in vivo models, we report that ATR-defective cells exhibit altered nuclear plasticity and YAP delocalization. When subjected to mechanical stress or undergoing interstitial migration, ATR-defective nuclei collapse accumulating nuclear envelope ruptures and perinuclear cGAS, which indicate loss of nuclear envelope integrity, and aberrant perinuclear chromatin status. ATR-defective cells also are defective in neuronal migration during development and in metastatic dissemination from circulating tumor cells. Our findings indicate that ATR ensures mechanical coupling of the cytoskeleton to the nuclear envelope and accompanying regulation of envelope-chromosome association. Thus the repertoire of ATR-regulated biological processes extends well beyond its canonical role in triggering biochemical implementation of the DNA damage response.
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