14 results on '"Nozza E"'
Search Results
2. Splicing factor 3B subunit 1 (SF3B1) role in PRL-secreting PitNETs
- Author
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Mangili, Federica, primary, Muro, Genesio Di, additional, Arlati, Federico, additional, Barbieri, Anna Maria, additional, E., G-Garcia Miguel, additional, Esposito, Emanuela, additional, Treppiedi, Donatella, additional, Catalano, Rosa, additional, Marra, Giusy, additional, Nozza, E mma, additional, Locatelli, Marco, additional, Lania, Andrea, additional, Ferrante, Emanuele, additional, Sala, Elisa, additional, P., Castano Justo, additional, M., Luque Raul, additional, Arosio, Maura, additional, Peverelli, Erika, additional, and Mantovani, Giovanna, additional more...
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- 2023
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Catalog
3. Study of the toxicological effect of winter and summer PM1 on BEAS-2B
- Author
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Melzi, G., Nozza, E., Crova, F., Valentini, S., Forello, A., Valli, G., Vecchi, R., Costabile, F., Marinovich, M., and Corsini, E.
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particulate matter ,oxidative stress ,genotoxicity ,inflammation ,BEAS-2B ,Settore BIO/14 - Farmacologia - Published
- 2022
4. P07-30 Study of the toxicological effect of winter and summer PM1 on BEAS-2B
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Melzi, G., primary, Nozza, E., additional, Crova, F., additional, Valentini, S., additional, Forello, A., additional, Valli, G., additional, Vecchi, R., additional, Costabile, F., additional, Marinovich, M., additional, and Corsini, E., additional more...
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- 2022
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5. Air Liquid Interface (ALI) system: genotoxic and inflammatory profile of BEAS-2B exposed in Bologna, Italy
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Nozza, E., primary, Melzi, G., additional, Gualtieri, M., additional, Corsini, E., additional, Costabile, F., additional, Moretto, A., additional, Vecchi, R., additional, and Marinovich, M., additional more...
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- 2021
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6. In vitro characterization of genotoxic damage induced by various PM sources on the bronchial epithelial cell line BEAS-2B
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Melzi, G., primary, Nozza, E., additional, A, M.A., additional, Canepari, S., additional, Corsini, E., additional, Vecchi, R., additional, and Marinovich, M., additional
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- 2021
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7. Therapeutic potential of targeting the FLNA-regulated Wee1 kinase in adrenocortical carcinomas.
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Esposito E, Marra G, Catalano R, Maioli S, Nozza E, Barbieri AM, Hantel C, Di Dalmazi G, Sigala S, Geginat J, Cassinotti E, Baldari L, Palmieri S, Mangone A, Berruti A, Ferrante E, Mantovani G, and Peverelli E more...
- Abstract
Filamin A (FLNA) is poorly expressed in adrenocortical carcinomas (ACC) compared to adenomas (ACA). Its presence is associated to a less aggressive tumour behaviour, potentially due to its role in negatively regulating IGF1R signalling. Upregulation of G2/M Wee1 kinase was shown in FLNA-deficient mouse neural progenitor cells, and it has been reported in several tumours. This study explored Wee1 expression in ACC and its regulation by FLNA, the effects of Wee1 inhibitor AZD1775, and the impact of FLNA on its efficacy in ACC cell lines and primary cells. Analysis of FLNA and Wee1 proteins revealed elevated Wee1 and reduced FLNA in ACC compared to normal adrenal gland. FLNA knockdown increased Wee1 protein in NCI-H295R, MUC-1, and in primary ACC cells. Higher p-CDK1 and cyclin B1 were shown in FLNA-silenced MUC-1, while decreased Wee1, p-CDK1 and cyclin B1 resulted after FLNA overexpression. Wee1 reduction was reverted by lactacystin treatment and FLNA transfection increased p-Wee1 (Ser123), suggesting FLNA's role in targeting Wee1 for degradation. AZD1775 dose-dependently reduced proliferation and viability in ACC cell lines and primary cultures, and it triggered MUC-1 cell death. Similar effects were induced by Wee1 silencing. FLNA depletion augmented AZD1775's efficacy in reducing proliferation and potentiating apoptosis in MUC-1 and primary cells. In conclusion, we demonstrated that FLNA regulates Wee1 expression by promoting its degradation, suggesting that low FLNA typical of ACC leads to increased Wee1 with consequent cancer cells growth. It proposes Wee1 inhibition as a new potential therapeutic approach for ACC, particularly for those lacking FLNA., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.) more...
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- 2024
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8. Redox-activity and in vitro effects of regional atmospheric aerosol pollution: Seasonal differences and correlation between oxidative potential and in vitro toxicity of PM 1 .
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Melzi G, Massimi L, Frezzini MA, Iulini M, Tarallo N, Rinaldi M, Paglione M, Nozza E, Crova F, Valentini S, Valli G, Costabile F, Canepari S, Decesari S, Vecchi R, Marinovich M, and Corsini E
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- Humans, Italy, Environmental Monitoring methods, THP-1 Cells, Reactive Oxygen Species metabolism, Particle Size, Cell Survival drug effects, Particulate Matter toxicity, Seasons, Oxidative Stress drug effects, Air Pollutants toxicity, Oxidation-Reduction, DNA Damage drug effects, Aerosols
- Abstract
Particulate Matter (PM) is a complex and heterogeneous mixture of atmospheric particles recognized as a threat to human health. Oxidative Potential (OP) measurement is a promising and integrative method for estimating PM-induced health impacts since it is recognized as more closely associated with adverse health effects than ordinarily used PM mass concentrations. OP measurements could be introduced in the air quality monitoring, along with the parameters currently evaluated. PM deposition in the lungs induces oxidative stress, inflammation, and DNA damage. The study aimed to compare the OP measurements with toxicological effects on BEAS-2B and THP-1 cells of winter and summer PM
1 collected in the Po Valley (Italy) during 2021. PM1 was extracted in deionized water by mechanical agitation and tested for OP and, in parallel, used to treat cells. Cytotoxicity, genotoxicity, oxidative stress, and inflammatory responses were assessed by MTT test, DCFH-DA assay, micronucleus, γ-H2AX, comet assay modified with endonucleases, ELISA, and Real-Time PCR. The evaluation of OP was performed by applying three different assays: dithiothreitol (OPDTT ), ascorbic acid (OPAA ), and 2',7'-dichlorofluorescein (OPDCFH ), in addition, the reducing potential was also analysed (RPDPPH ). Seasonal differences were detected in all the parameters investigated. The amount of DNA damage detected with the Comet assay and ROS formation highlights the presence of oxidative damage both in winter and in summer samples, while DNA damage (micronucleus) and genes regulation were mainly detected in winter samples. A positive correlation with OPDCFH (Spearman's analysis, p < 0.05) was detected for IL-8 secretion and γ-H2AX. These results provide a biological support to the implementation in air quality monitoring of OP measurements as a useful proxy to estimate PM-induced cellular toxicological responses. In addition, these results provide new insights for the assessment of the ability of secondary aerosol in the background atmosphere to induce oxidative stress and health effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) more...- Published
- 2024
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9. The Novel SSTR3 Agonist ITF2984 Exerts Antimitotic and Proapoptotic Effects in Human Non-Functioning Pituitary Neuroendocrine Tumor (NF-PitNET) Cells.
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Di Muro G, Catalano R, Treppiedi D, Barbieri AM, Mangili F, Marra G, Di Bari S, Esposito E, Nozza E, Lania AG, Ferrante E, Locatelli M, Modena D, Steinkuhler C, Peverelli E, and Mantovani G
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- Humans, Octreotide pharmacology, Octreotide therapeutic use, Receptors, Somatostatin genetics, Antimitotic Agents, Neuroendocrine Tumors drug therapy, Pituitary Neoplasms drug therapy, Pituitary Neoplasms genetics
- Abstract
Somatostatin receptor ligands (SRLs) with high affinity for somatostatin receptors 2 and 5 (SSTR2 and SSTR5) are poorly efficacious in NF-PitNETs, expressing high levels of SSTR3. ITF2984 is a pan-SSTR ligand with high affinity for SSTR3, able to induce SSTR3 activation and to exert antitumoral activity in the MENX rat model. The aim of this study was to test ITF2984's antiproliferative and proapoptotic effects in NF-PitNET primary cultured cells derived from surgically removed human tumors and to characterize their SSTR expression profile. We treated cells derived from 23 NF-PitNETs with ITF2984, and a subset of them with octreotide, pasireotide (SRLs with high affinity for SSTR2 or 5, respectively), or cabergoline (DRD2 agonist) and we measured cell proliferation and apoptosis. SSTR3, SSTR2, and SSTR5 expression in tumor tissues was analyzed by qRT-PCR and Western blot. We demonstrated that ITF2984 reduced cell proliferation (-40.8 (17.08)%, p < 0.001 vs. basal, n = 19 NF-PitNETs) and increased cell apoptosis (+41.4 (22.1)%, p < 0.001 vs. basal, n = 17 NF-PitNETs) in all tumors tested, whereas the other drugs were only effective in some tumors. In our model, SSTR3 expression levels did not correlate with ITF2984 antiproliferative nor proapoptotic effects. In conclusion, our data support a possible use of ITF2984 in the pharmacological treatment of NF-PitNET. more...
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- 2024
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10. High Filamin a Expression in Adrenocortical Carcinomas Is Associated with a Favourable Tumour Behaviour: A European Multicentric Study.
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Catalano R, Altieri B, Angelousi A, Arosio M, Bravi F, Canu L, Croci GA, Detomas M, Esposito E, Ferrante E, Ferrero S, Fuss CT, Kaltsas G, Kimpel O, Landwehr LS, Luconi M, Morelli V, Nesi G, Nozza E, Sbiera S, Serban AL, Ronchi CL, Mantovani G, and Peverelli E more...
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- Humans, Signal Transduction, Prognosis, Adrenal Cortex Neoplasms diagnosis, Adrenocortical Adenoma diagnosis, Adrenocortical Carcinoma diagnosis, Filamins genetics, Filamins metabolism
- Abstract
The insulin-like growth factor 2 (IGF2) promotes cell growth by overactivating the IGF system in an autocrine loop in adrenocortical carcinomas (ACCs). The cytoskeleton protein filamin A (FLNA) acts as a repressor of IGF2 mitogenic signalling in ACC cells. The aims of this study were to test FLNA expression by immunohistochemistry in 119 ACCs and 26 adrenocortical adenomas (ACAs) and to evaluate its relationship with clinicopathological features and outcome in ACCs. We found that 71.4% of ACCs did not express FLNA, whereas FLNA absence was a rare event in ACAs (15.4%, p < 0.001 vs. ACCs). In addition, the expression of FLNA was associated with a less aggressive tumour behaviour in ACCs. Indeed, the subgroup of ACCs with high FLNA showed a lower ENSAT stage, Weiss score, and S-GRAS score compared to ACCs with low FLNA expression ( p < 0.05). Moreover, patients with high FLNA had a longer overall survival than those with low FLNA ( p < 0.05). In conclusion, our data suggest that FLNA may represent a "protective" factor in ACCs, and the integration of FLNA immunohistochemical expression in ACC tissues along with other clinical and molecular markers could be helpful to improve diagnostic accuracy and prognosis prediction in ACCs. more...
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- 2023
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11. A β-Arrestin 2-Biased Dopamine Receptor Type 2 (DRD2) Agonist Is More Efficacious Than Cabergoline in Reducing Cell Proliferation in PRL-Secreting but Not in Non-Functioning Pituitary Tumor Cells.
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Di Muro G, Mangili F, Esposito E, Barbieri AM, Catalano R, Treppiedi D, Marra G, Nozza E, Lania AGA, Ferrante E, Locatelli M, Arosio M, Peverelli E, and Mantovani G
- Abstract
The molecular events underlying the variable effectiveness of dopamine receptor type 2 (DRD2) agonists in pituitary neuroendocrine tumors (PitNETs) are not known. Besides the canonical pathway induced by DRD2 coupling with Gi proteins, the β-arrestin 2 pathway contributes to DRD2's antimitotic effects in PRL- and NF-PitNETs. A promising pharmacological strategy is the use of DRD2-biased agonists that selectively activate only one of these two pathways. The aim of the present study was to compare the effects of two biased DRD2 ligands, selectively activating the G protein (MLS1547) or β-arrestin 2 (UNC9994) pathway, with unbiased DRD2 agonist cabergoline in PRL- and NF-PitNET cells. In rat tumoral pituitary PRL-secreting MMQ cells, UNC9994 reduced cell proliferation with a greater efficacy compared to cabergoline (-40.2 ± 20.4% vs. -21 ± 10.9%, p < 0.05), whereas the G-protein-biased agonist induced only a slight reduction. β-arrestin 2 silencing, but not pertussis toxin treatment, reverted UNC9994 and cabergoline's antiproliferative effects. In a cabergoline-resistant PRL-PitNET primary culture, UNC9994 inhibited cell proliferation and PRL release. In contrast, in NF-PitNET primary cultures ( n = 23), biased agonists did not show better antiproliferative effects than cabergoline. In conclusion, the preferential activation of the β-arrestin 2 pathway by UNC9994 improves DRD2-mediated antiproliferative effects in PRL-PitNETs, suggesting a new pharmacological approach for resistant or poorly responsive tumors. more...
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- 2023
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12. Toxicological Profile of PM from Different Sources in the Bronchial Epithelial Cell Line BEAS-2B.
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Melzi G, Nozza E, Frezzini MA, Canepari S, Vecchi R, Cremonesi L, Potenza M, Marinovich M, and Corsini E
- Abstract
The toxicity of particulate matter (PM) is strictly associated with its physical-chemical characteristics, such as size or chemical composition. While these properties depend on the origin of the particles, the study of the toxicological profile of PM from single sources has rarely been highlighted. Hence, the focus of this research was to investigate the biological effects of PM from five relevant sources of atmospheric PM: diesel exhaust particles, coke dust, pellet ashes, incinerator ashes, and brake dust. Cytotoxicity, genotoxicity, oxidative, and inflammatory response were assessed in a bronchial cell line (BEAS-2B). BEAS-2B cells were exposed to different concentrations (25, 50, 100, and 150 μg/mL medium) of particles suspended in water. The exposure lasted 24 h for all the assays performed, except for reactive oxygen species, which were evaluated after 30 min, 1 h, and 4 h of treatment. The results showed a different action of the five types of PM. All the tested samples showed a genotoxic action on BEAS-2B, even in the absence of oxidative stress induction. Pellet ashes seemed to be the only ones able to induce oxidative stress by boosting the formation of reactive oxygen species, while brake dust resulted in the most cytotoxic. In conclusion, the study elucidated the differential response of bronchial cells to PM samples generated by different sources. The comparison could be a starting point for a regulatory intervention since it highlighted the toxic potential of each type of PM tested. more...
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- 2023
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13. P720R USP8 Mutation Is Associated with a Better Responsiveness to Pasireotide in ACTH-Secreting PitNETs.
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Treppiedi D, Marra G, Di Muro G, Esposito E, Barbieri AM, Catalano R, Mangili F, Bravi F, Locatelli M, Lania AG, Ferrante E, Indirli R, Nozza E, Arlati F, Spada A, Arosio M, Mantovani G, and Peverelli E more...
- Abstract
Somatic mutations in the ubiquitin specific peptidase 8 (USP8) gene have been associated with higher levels of somatostatin (SS) receptor subtype 5 (SSTR5) in adrenocorticotroph hormone (ACTH)-secreting pituitary neuroendocrine tumors (PitNETs). However, a correlation between the USP8 mutational status and favourable responses to pasireotide, the somatostatin multi-receptor ligand acting especially on SSTR5, has not been investigated yet. Here, we studied the impact of USP8 mutations on pasireotide responsiveness in human and murine corticotroph tumor cells. SSTR5 upregulation was observed in USP8 wild-type primary tumor cells transfected with S718del USP8 mutant. However, cell transfection with S718del USP8 and C40-USP8 mutants in in vitro sensitive cultures from USP8 wild-type tumors abolished their ability to respond to pasireotide and did not confer pasireotide responsiveness to the in vitro resistant culture. Pasireotide failed to reduce ACTH secretion in primary cells from one S718P USP8-mutated tumor but exerted a strong antisecretory effect in primary cells from one P720R USP8-mutated tumor. In agreement, AtT-20 cells transfection with USP8 mutants led to SSTR5 expression increase but pasireotide could reduce ACTH production and cyclin E expression in P720R USP8 overexpressing cells, only. In situ Proximity Ligation Assay and immunoflurescence experiments revealed that P720R USP8 mutant is still able to bind 14-3-3 proteins in AtT-20 cells, without affecting SSTR5 localization. In conclusion, P720R USP8 mutation might be considered as a molecular predictor of favourable response to pasireotide in corticotroph tumor cells. more...
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- 2022
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14. Rhus coriaria L. Fruit Extract Prevents UV-A-Induced Genotoxicity and Oxidative Injury in Human Microvascular Endothelial Cells.
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Nozza E, Melzi G, Marabini L, Marinovich M, Piazza S, Khalilpour S, Dell'Agli M, and Sangiovanni E
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Rhus coriaria L. (sumac) is a small plant widely diffused in the Mediterranean region. Its fruit are often consumed as a spice but are also present in traditional medicine of several countries. Recently, interest in this plant has increased and many scientific works reported its beneficial effects including antioxidant and anti-inflammatory properties. Plant extracts can be successfully used against ultraviolet rays, which are able to reach and damage the human skin; however, sumac extracts were never applied to this usage. Thus, in this study, we used a macerated ethanol extract of Rhus coriaria L. dried fruit (mERC) to demonstrate its preventive role against the damage induced by ultraviolet-A rays (UV-A) on microvascular endothelial cells (HMEC-1). In vitro effects of the extract pre-treatment and UV-A exposure were evaluated in detail. The antioxidant capacity was assessed by reactive oxygen species (ROS) formation and cellular antioxidant activity measurement. Genoprotective effects of mERC were investigated as well. Our findings indicate that the extract acts as a cell cycle inhibitor or apoptosis inducer, according to the level of damage. The present work provides new insights into the usage of Rhus coriaria extracts against skin injuries. more...
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- 2020
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