| 1. |
- Bettiga, Arianna, et al.
(författare)
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Bladder cancer cell growth and motility implicate cannabinoid 2 receptor-mediated modifications of sphingolipids metabolism
- 2017
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The inhibitory effects demonstrated by activation of cannabinoid receptors (CB) on cancer proliferation and migration may also play critical roles in controlling bladder cancer (BC). CB expression on human normal and BC specimens was tested by immunohistochemistry. Human BC cells RT4 and RT112 were challenged with CB agonists and assessed for proliferation, apoptosis, and motility. Cellular sphingolipids (SL) constitution and metabolism were evaluated after metabolic labelling. CB1-2 were detected in BC specimens, but only CB2 was more expressed in the tumour. Both cell lines expressed similar CB2. Exposure to CB2 agonists inhibited BC growth, down-modulated Akt, induced caspase 3-activation and modified SL metabolism. Baseline SL analysis in cell lines showed differences linked to unique migratory behaviours and cytoskeletal re-arrangements. CB2 activation changed the SL composition of more aggressive RT112 cells by reducing (p amp;lt; 0.01) Gb3 ganglioside (-50 +/- 3%) and sphingosine 1-phosphate (S1P, -40 +/- 4%), which ended up to reduction in cell motility (-46 +/- 5%) with inhibition of p-SRC. CB2-selective antagonists, gene silencing and an inhibitor of SL biosynthesis partially prevented CB2 agonist-induced effects on cell viability and motility. CB2 activation led to ceramide-mediated BC cell apoptosis independently of SL constitutive composition, which instead was modulated by CB2 agonists to reduce cell motility.
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| 2. |
- Gambardella, Chiara, et al.
(författare)
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New insights into the impact of leachates from in-field collected plastics on aquatic invertebrates and vertebrates
- 2024
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Ingår i: Environmental Pollution. - : Springer. - 0269-7491 .- 1873-6424.
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Tidskriftsartikel (refereegranskat)abstract
- The impact of leachates from micronized beached plastics of the Mediterranean Sea and Atlantic Ocean on coastal marine ecosystems was investigated by using a multidisciplinary approach. Chemical analysis and ecotoxicological tests on phylogenetically distant species were performed on leachates from the following plastic categories: bottles, pellets, hard plastic (HP) containers, fishing nets (FN) and rapido trawling rubber (RTR). The bacteria Alivibrio fischeri, the nauplii of the crustaceans Amphibalanus amphitrite and Acartia tonsa, the rotifer Brachionus plicatilis, the embryos of the sea urchin Paracentrotus lividus, the ephyrae of the jellyfish Aurelia sp. and the larvae of the medaka Oryzias latipes were exposed to different concentrations of leachates to evaluate lethal and sub-lethal effects. Thirty-one additives were identified in the plastic leachates; benzophenone, benzyl butyl phthalate and ethylparaben were present in all leachates. Ecotoxicity of leachates varied among plastic categories and areas, being RTR, HP and FN more toxic than plastic bottles and pellets to several marine invertebrates. The ecotoxicological results based on 13 endpoints were elaborated within a quantitative weight of evidence (WOE) model, providing a synthetic hazard index for each data typology, before their integrations in an environmental risk index. The WOE assigned a moderate and slight hazard to organisms exposed to leachates of FN and HP collected in the Mediterranean Sea respectively, and a moderate hazard to leachates of HP from the Atlantic Ocean. No hazard was found for pellet, bottles and RTR. These findings suggest that an integrated approach based on WOE on a large set of bioassays is recommended to get a more reliable assessment of the ecotoxicity of beached-plastic leachates. In addition, the additives leached from FN and HP should be further investigated to reduce high concentrations and additive types that could impact marine ecosystem health.
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| 3. |
- Maclachlan, Kylee, et al.
(författare)
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Second malignancies in multiple myeloma; emerging patterns and future directions
- 2020
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Ingår i: Best Practice and Research: Clinical Haematology. - : Elsevier BV. - 1521-6926. ; 33:1
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Forskningsöversikt (refereegranskat)abstract
- The changing landscape of treatment options for multiple myeloma has led to a higher proportion of patients achieving deep, long-lasting responses to therapy. With the associated improvement in overall survival, the development of subsequent second malignancies has become of increased significance. The risk of second malignancy after multiple myeloma is affected by a combination of patient-, disease- and therapy-related risk factors. This review discusses recent data refining our knowledge of these contributing factors, including current treatment modalities which increase risk (i.e. high-dose melphalan with autologous stem cell transplant and lenalidomide maintenance therapy). We highlight emerging data towards individualized risk- and response-adapted treatment strategies and discuss key areas requiring future research.
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| 4. |
- Meli, Valeri, et al.
(författare)
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Theranostic hexosomes for cancer treatments : an in vitro study
- 2017
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Ingår i: New Journal of Chemistry. - : Royal Society of Chemistry (RSC). - 1144-0546 .- 1369-9261. ; 41:4, s. 1558-1565
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Tidskriftsartikel (refereegranskat)abstract
- We have formulated and investigated innovative lipid-based nanoparticles characterized by a reverse hexagonal liquid crystalline inner structure (hexosomes). These nanoparticles were doped with a potent, highly water insoluble anticancer drug, namely docetaxel, and stabilized by a mixture of commercial and folate- and rhodamine-conjugated Pluronic F108. Thus, they simultaneously possess therapeutic, imaging, and targeting properties toward cancer cells. The morphological and structural aspects of the hexosomes were investigated at different temperatures (10, 25, 37, and 50 °C), and our results demonstrate good performance in terms of stability of these nanoparticles. The latter was furthermore confirmed by the very slow and continuous release profile of docetaxel observed in drug release experiments. Although it was not possible to assess a specific compartmentalization of the dye, this formulation allowed the successful visualization of HeLa cells. Finally, cytotoxic assays showed a 20-fold higher toxic effect of the drug-doped hexosomes against HeLa cells with respect to the free (not loaded in hexosomes) anticancer drug. On the whole, these results indicate that this formulation is a potential theranostic tool in oncology.
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| 5. |
- Montesarchio, Valeria, et al.
(författare)
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Comparison of methodologies for flood rainfall thresholds estimation
- 2015
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Ingår i: Natural Hazards. - : Springer Netherlands. - 0921-030X .- 1573-0840. ; 75:1, s. 909-934
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Tidskriftsartikel (refereegranskat)abstract
- A flood warning system based on rainfall thresholds makes it possible to issue alarms via an off-line approach. This technique is useful for mitigating the effects of flooding in small-to-medium-sized basins characterized by an extremely rapid response to rainfall. Rainfall threshold values specify the amount of precipitation that occurs over a given period of time and are dependent on both the amount of soil moisture and the spatiotemporal distribution of the rainfall. The precipitation generates a critical discharge in a particular river cross section. Exceeding these values can produce a critical situation in river sites that make them susceptible to flooding. In this work, we present a comparison of methodologies for estimating rainfall thresholds. Critical precipitation amounts are evaluated using empirical data, hydrological simulations and probabilistic methods. The study focuses on three small-to-medium-sized basins located in central Italy. For each catchment, historical data are first used to theoretically evaluate the empirical rainfall thresholds. Next, we calibrate a semi-distributed hydrological model that is validated using rain gauge and weather radar data. Critical rainfall depths over 30 min and 1, 3, 6, 12 and 24 h durations are then evaluated using the hydrological simulation. In the probabilistic approach, rainfall threshold values result from a minimization of two different functions, one following the Bayesian decision theory and the other following the informative entropy concept. In order to implement both functions, it is necessary to evaluate the joint probability function. The joint probability function is built up as a bivariate distribution of rainfall depth for a given duration with the corresponding flow peak value. Finally, in order to assess the performance of each methodology, we construct contingency tables to highlight the system performance.
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| 9. |
- Vilke, Juliano M., et al.
(författare)
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Looking beyond the obvious : The ecotoxicological impact of the leachate from fishing nets and cables in the marine mussel Mytilus galloprovincialis
- 2024
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Ingår i: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 473
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Tidskriftsartikel (refereegranskat)abstract
- Once in the marine environment, fishing nets and cables undergo weathering, breaking down into micro and nano-size particles and leaching plastic additives, which negatively affect marine biota. This study aims to unravel the ecotoxicological impact of different concentrations of leachate obtained from abandoned or lost fishing nets and cables in the mussel Mytilus galloprovincialis under long-term exposure (28 days). Biochemical biomarkers linked to antioxidant defense system, xenobiotic biotransformation, oxidative damage, genotoxicity, and neurotoxicity were evaluated in different mussel tissues. The chemical nature of the fishing nets and cables and the chemical composition of the leachate were assessed and metals, plasticizers, UV stabilizers, flame retardants, antioxidants, dyes, flavoring agents, preservatives, intermediates and photo initiators were detected. The leachate severely affected the antioxidant and biotransformation systems in mussels' tissues. Following exposure to 1 mg·L-1 of leachate, mussels' defense system was enhanced to prevent oxidative damage. In contrast, in mussels exposed to 10 and 100 mg·L-1 of leachate, defenses failed to overcome pro-oxidant molecules, resulting in genotoxicity and oxidative damage. Principal component analysis (PCA) and Weight of Evidence (WOE) evaluation confirmed that mussels were significantly affected by the leachate being the hazard of the leachate concentrations of 10 mg·L-1 ranked as major, while 1 and 100 mg·L-1 was moderate. These results highlighted that the leachate from fishing nets and cables can be a threat to the heath of the mussel M. galloprovincialis.
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