43 results on '"Bizzozero L"'
Search Results
2. Environmental occurrence of organophosphate esters and micro-plastics in sediments and benthic organisms from the Loire Estuary (France)
- Author
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Castro-Jimenez, Javier, Aminot, Y, Pollono, C, Idjaton, B, Bizzozero, L, Pierre-Duplessix, O, Phuong, N.N., Gasperi, Johnny, and Cadic, Ifsttar
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ORGANOPHOSPHATE ESTER (OPE) FLAME RETARDANT ,MICROPLASTIQUE ,POLLUTION DES EAUX ,[SDE.MCG] Environmental Sciences/Global Changes ,MICROPLASTIC ,LOIRE ,PHOSPHORE ,ESTUAIRE ,POLLUTION CHIMIQUE ,PLASTIQUE - Abstract
Organophosphate ester (OPE) flame retardants and plasticizers and microplastics (MPs) are emerging threats to the marine environment, presenting multiple sources in the environment and being widely distributed in sea and ocean of the planet. Marine sediments are thought to be a sink for both OPEs and MPs. In addition, leaching from MPs could constitute in-situ sources of OPEs. Therefore, determining their environmental occurrence in sediments becomes crucial to better understand their current stocks, the exposure of benthic organisms, and possible impacts on the global functioning of marine ecosystems. The Loire is the longest river in France representing an important freshwater discharge to the North-East Atlantic Ocean. Its estuary is considered as an ecosystem of high ecological value as well as an ocean/land interface for sea trade and associated industrial activities. The overall objectives of this work were: (1) to determine the current environmental levels of OPEs and MPs in sediments and selected benthic organisms from the Loire estuary; (2) to investigate the OPE bioaccumulation (transfer sediment-benthos); and (3) to explore the links between MPs abundance and OPE concentrations in the study area. Two sampling campaigns conducted in September 2021 and November 2022 allowed the collection of surface sediments and the deposit feeder clam Scrobicularia plana (SP) in four study areas subjected to different anthropogenic pressures. Preliminary results from the first campaign in September are presented in this poster.
- Published
- 2022
3. Aneurysms of the vertebro-basilar junction area: Preliminary experience in endovascular and surgical management
- Author
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Collice, M., Arena, O., D’Aliberti, G., Todaro, C., Branca, V., Boccardi, E., Versari, P. P., Bizzozero, L., and Talamonti, G.
- Published
- 1997
- Full Text
- View/download PDF
4. Acid sphingomyelinase determines melanoma progression and metastatic behaviour via the microphtalmia-associated transcription factor signalling pathway
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Bizzozero, L, Cazzato, D, Cervia, D, Assi, E, Simbari, F, Pagni, F, De Palma, C, Monno, A, Verdelli, C, Querini, P, Russo, V, Clementi, E, Perrotta, C, PAGNI, FABIO, Querini, PR, Perrotta, C., Bizzozero, L, Cazzato, D, Cervia, D, Assi, E, Simbari, F, Pagni, F, De Palma, C, Monno, A, Verdelli, C, Querini, P, Russo, V, Clementi, E, Perrotta, C, PAGNI, FABIO, Querini, PR, and Perrotta, C.
- Abstract
Melanoma is a rapidly growing and highly metastatic cancer with high mortality rates, for which a resolutive treatment is lacking. Identification of novel therapeutic strategies and biomarkers of tumour stage is thus of particular relevance. We report here on a novel biomarker and possible candidate therapeutic target, the sphingolipid metabolising enzyme acid sphingomyelinase (A-SMase). A-SMase expression correlates inversely with tumour stage in human melanoma biopsies. Studies in a mouse model of melanoma and on cell lines derived from mouse and human melanomas demonstrated that A-SMase levels of expression actually determine the malignant phenotype of melanoma cells in terms of pigmentation, tumour progression, invasiveness and metastatic ability. The action of A-SMase is mediated by the activation of the extracellular signal-regulated kinase, the subsequent proteasomal degradation of the Microphtalmia-associated transcription factor (Mitf) and inhibition of cyclin-dependent kinase 2, Bcl-2 and c-Met, downstream targets of Mitf involved in tumour cell proliferation, survival and metastatisation
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- 2014
5. Identifying patients at risk for microalbuminuria via interaction of the components of the metabolic syndrome: a cross-sectional analytic study
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Gentile, L., Cichero, P., Di Berardino, P., Di Petta, C., Montani, V., Poli, M., Grosso, J., De Marco, F., Perticone, F., Mattace, A., Vatrano, M., Ventura, G., Sprovieri, M., Spagnuolo, V., Mastropasqua, A., Marenco, P., Caruso, M., D’Ugo, E., Squadrone, M. R., Pupillo, M., Minnucci, A., De Luca, A., Tagliaferri, M., Vitale, C., Sciangula, L., Banfi, E., Cucinotta, D., Dibenedetto, A., Previti, M., Tiengo, A., Avogaro, A., Bettio, M., Dekreuzenberg, S., Galluzzo, A., Camilleri, C., Merlino, S., Sinagra, D., Provenzano, V., Fleres, M., Carnovali, M., Crespi, E., Sommariva, M., Vecchio, C., Consoli, A., Ciccarone, E., Devangelio, E., Formoso, G., Taraborrelli, M., Seghieri, G., Alviggi, L., Bardini, G., De Bellis, A., Porro, T., Bianchi, A., Dagani, R., Di Battista, R., Ferrario, A., Ottaviano, R., Gambardella, S., Bracaglia, D., Testa, G., Mancini, A., Giannini, D., Monesi, G., Mollo, F., Osti, M., Di Michele, D., Lattanzi, E., Piersanti, C., Ghigo, E., Camanni, F., Destefanis, S., Gaia, D., Gasco, V., Maccario, M., Carretta, R., Fiammengo, F., Gerloni, R., Macaluso, L., Donnini, P., Alvaro, S., Ambrosio, G. B., Leprotti, C., Moro, E., Pais, M., Pianetti, S., Garbin, A., Frascone, V., Marmo, P., Munari, G. F., Cataldi, B., Filiani, M. L., Ursini, G., Augello, M., Tassan, P., Giraldi, D., Berarducci, G., Braggion, M., Novelletto, B. F., Dell’Orco, R. L., Baj, A., Pardo, S., Persia, M., Bellini, F., Nistico, F., Rossi, C. L., Quinzii, G., Ferrigato, A., Zaramella, M. L., Crisante, E., Biundo, G., Serughetti, G., Sofra, D., Trono, L., Arduino, G., Chiappetta, S., Novarese, I., Monari, M., Cappello, I., Lipari, L., Bersani, G. P., Marcomini, G., Felici, M. G., Bragiotto, A., Felice, L., Caberletti, I., Vergani, P., Orecchia, E., Ferracin, F., Cavallo, G., Giardina, L., Felloni, L., Cesarone, L., Albanese, V., Bizzozero, L., Cerati, C., Mauri, L., Ratti, C., Alecci, U., Alibrando, A., Forastiere, G., Petrella, G., Di Mattia, Q., Grimaldi, N., Olivieri, I., Cardella, M. C., Duren, B., Falzone, A., Furlan, G., Nesladek, N., Novel, N., Pasquariello, M., Russo, M., Veglia, D., Fusello, M., Baldi, C., Seller, R., Tosi, G., Barberio, S., Tonon, R., Cardinale, G., Lombardo, F. P., Magliozzo, F., Merlino, G., Merlino, N., Quartetti, G., Bolognese, F., Baglieri, S., Giarrusso, P., Speciale, S., Buffone, M., Di Domizio, O., Panzieri, F., Perfetto, G., Granati, A., Lattari, P. R., Potenti, P. G., Quattrocchi, M., Vannucci, R., Daddi, L., Dallatorre, G., Guido, G. P., Orlando, F., Santoro, A., Zagni, R., Genova, O., Alaimo, A., Canfora, M., Cappelli, C., Caracciolo, F., Casimirri, R., Crestini, A. M., Daniele, G., De Lucia, L., Demarchis, A., Di Masi, A., Di Rosa, F., Filabozzi, A., Levati, M., Lucente, A., Manzo, G., Marchionne, M., Marino, G. A., Paolini, E., Quaresima, M., Scala, P., Scotto, M., Scotto, R., Simeoni, A., Chieregato, G., Sparesato, S., Cavallo, E., Ceglia, G., Chiarini, T., Visentini, E., Sammarone, R., Di Giambattista, P., Fumagalli, M. A., Milanese, F., Santoro, L., Giusti, P., Nafra, G., Romito, G., Balsamo, R., Rinaldi, M., Biondo, F., Consiglio, G., Arbore, G., Garione, I., Merlini, C., Pizzini, A., Titta, G., Vitali, S., Rotondo, G., Berardi, A., Castellani, G., Cova, L. V., Lamberti, C., Granzotto, S., Mazzi, P. A., Bergamasco, G., Autiero, V., and L. Ghiraldelli.
- Subjects
Male ,medicine.medical_specialty ,Multivariate analysis ,endocrine system diseases ,Epidemiology ,Population ,urologic and male genital diseases ,Critical Care and Intensive Care Medicine ,Impaired glucose tolerance ,Insulin resistance ,Risk Factors ,Diabetes mellitus ,Internal medicine ,medicine ,Albuminuria ,Humans ,education ,Aged ,Metabolic Syndrome ,Transplantation ,education.field_of_study ,business.industry ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,female genital diseases and pregnancy complications ,Endocrinology ,Cross-Sectional Studies ,Nephrology ,Homogeneous ,Microalbuminuria ,Female ,Metabolic syndrome ,business - Abstract
The objective of this study was to investigate correlates of risk for having microalbuminuria in individuals with one or more cardiovascular risk factors.The study involved 1919 individuals who attended general practice settings, were aged 55 to 75 yr, and did not have a history of cardiovascular events or diabetes but had one or more cardiovascular risk factors. A tree-based regression technique and multivariate analysis were used to identify distinct, homogeneous subgroups of patients with different likelihood of having microalbuminuria; interaction between correlates of microalbuminuria and risk for microalbuminuria was also investigated.The prevalence of microalbuminuria was 5.9%. Patients who did not have hypertension and had postload glycemia140 mg/dl showed the lowest prevalence of microalbuminuria (1.9%) and represented the reference class. The likelihood of microalbuminuria was seven times higher in men with hypertension and homeostatic model assessment levels in the upper tertile and four times higher in women with the same characteristics. Individuals with hypertension and lower homeostatic model assessment levels and normotensive individuals with postload glycemiaor = 140 mg/dl had a more than three-fold increased likelihood of having microalbuminuria. Treatment with statins was associated with a 54% reduction in the likelihood of having microalbuminuria, whereas levels of triglycerides150 mg/dl and fibrinogen levels in the upper tertile were associated with a significantly higher risk for microalbuminuria.The likelihood of having microalbuminuria in a population-based study of elderly individuals is strongly related to the interaction between the components of the metabolic syndrome, particularly hypertension, insulin resistance, and impaired glucose tolerance.
- Published
- 2007
6. Use of the Diabetes Risk Score for Opportunistic Screening of Undiagnosed Diabetes and Impaired Glucose Tolerance: The IGLOO (Impaired Glucose Tolerance and Long-Term Outcomes Observational) study
- Author
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Muggeo, M., Caimi, V., Capani, F., Cucinotta, D., Grimaldi, N., Montanari, P., Mocarelli, P., Signorini, S., Dinardo, B., Ferrari, S., Piaggione, M., Gentile, L., Cichero, P., Di Berardino, P., Di Petta, C., Montani, V., Poli, M., Grosso, J., De Marco, F., Perticone, F., Mattace, A., Vatrano, M., Ventura, G., Sprovieri, M., Spagnuolo, V., Mastropasqua, A., Marenco, P., D’Ugo, E., Squadrone, M. R., Pupillo, M., De Luca, A., Mennucci, A., Tagliaferri, M., Vitale, C., Sciangula, L., Banfi, E., Di Benedetto, A., Previti, M., Tiengo, A., Avogaro, A., Bettio, De Kreuzenberg, S., Galluzzo, A., Camilleri, C., Merlino, S., Sinagra, D., Provenzano, V., Fleres, M., Spano, L., Carnovali, M., Crespi, E., Sommariva, M., Vecchio, C., Consoli, A., Ciccarone, E., Devangelio, E., Formoso, G., Seghieri, G., Alviggi, L., Bardini, G., De Bellis, A., Porro, T., Bianchi, A., Dagani, R., Di Battista, R., Ferrario, Gambardella, S., Bracaglia, D., Testa, G., Giannini, D., Mancini, A., Monesi, G., Mollo, F., Osti, M., Di Michele, D., Lattanzi, E., Piersanti, C., Ghigo, E., Camanni, F., Destefanis, S., Gaia, D., Gasco, V., Maccario, M., Carretta, R., Fiammengo, F., Gerloni, R., Macaluso, L., Donnini, P., Alvaro, S., Ambrosio, G. B., Leprotti, C., Moro, E., Pais, M., Pianetti, S., Garbin, A., Frascone, V., Marmo, P., Munari, G. F., Cataldi, B., Ursini, G., Augello, M., Braggion, M., Baj, A., Persia, M., Nistico’, F., Rossi, C. L., Quinzii, G., Ferrigato, A., Zaramella, M. L., Serughetti, G., Sofra, D., Arduino, G., Chiappetta, S., Novarese, I., Monari, M., Cappello, I., Lipari, L., Marcomini, G., Felice, L., Caberletti, I., Vergani, P., Orecchia, E., Ferracin, F., Cavallo, G., Giardina, L., Felloni, L., Cesarone, L., Bizzozero, L., Ratti, C., Alecci, U., Marino, S., Forastiere, G., Petrella, G., Olivieri, I., Cardella, M. C., Duren, B., Furlan, G., Novel, N., Pasquariello, M., Russo, M., Baldi, C., Seller, R., Tosi, G., Barberio, S., Cardinale, G., Lombardo, F. P., Magliozzo, F., Merlino, G., Merlino, N., Quartetti, G., Bolognese, F., Baglieri, S., Speciale, S., Buffone, M., Di Domizio, O., Panzieri, F., Perfetto, G., Potenti, P. G., Quattrocchi, M., Vannucci, R., Daddi, L., Guido, G. P., Orlando, F., Santoro, A., Zagni, R., Canfora, M., Cappelli, C., Caracciolo, F., Casimirri, R., Crestini, A. M., De Marchis, A., Di Masi, A., Lucente, A., Manzo, G., Marchionne, M., Marino, G. A., Paolini, E., Scala, P., Scotto, M., Scotto, R., Simeoni, A., Chieregato, G., Cavallo, E., Ceglia, G., Chiarini, T., Visentini, E., Sammarone, R., Fumagalli, M. A., Milanese, F., Giusti, P., Balsamo, R., Rinaldi, M., Biondo, F., Consiglio, G., Garione, I., Merlini, C., Pizzini, A., Titta, G., Vitali, S., Rotondo, G., Cova, L. V., Lamberti, C., Granzotto, S., Mazzi, P. A., and Ghiraldelli, L.
- Published
- 2005
7. Acid sphingomyelinase determines melanoma progression and metastatic behaviour via the microphtalmia-associated transcription factor signalling pathway
- Author
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Bizzozero, L, primary, Cazzato, D, additional, Cervia, D, additional, Assi, E, additional, Simbari, F, additional, Pagni, F, additional, De Palma, C, additional, Monno, A, additional, Verdelli, C, additional, Querini, P R, additional, Russo, V, additional, Clementi, E, additional, and Perrotta, C, additional
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- 2013
- Full Text
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8. Head-Injured Patients Who Talk and Deteriorate
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Versari Pp, Giuseppe Talamonti, Bizzozero L, Romero A. Fontana, and Massimo Collice
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medicine.medical_specialty ,Physical medicine and rehabilitation ,business.industry ,Head (linguistics) ,medicine ,business - Published
- 1992
9. Dermoid cyst mimicking hematoma in the posterior fossa
- Author
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Bizzozero, L., primary, Talamonti, G., additional, D'Angelo, V.A., additional, Casadei, G.P., additional, Arrigoni, G.L., additional, and Collice, M., additional
- Published
- 1992
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10. Cerebral metastasis from an epithelioid malignant schwannoma
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D??Angelo, V, primary, Casadei, G, additional, and Bizzozero, L, additional
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- 1991
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11. Nitric Oxide Boosts Chemoimmunotherapy via Inhibition of Acid Sphingomyelinase in a Mouse Model of Melanoma
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Alessandro Prinetti, Angelo A. Manfredi, Sestina Falcone, Emilio Clementi, Laura Bizzozero, Patrizia Rovere-Querini, Edward H. Schuchman, Sandro Sonnino, Cristiana Perrotta, Perrotta, C, Bizzozero, L, Falcone, S, ROVERE QUERINI, Patrizia, Prinetti, A, Schuchman, Eh, Sonnino, S, Manfredi, ANGELO ANDREA M. A., and Clementi, E.
- Subjects
Cancer Research ,Ceramide ,Melanoma, Experimental ,Isosorbide Dinitrate ,Immunotherapy, Adoptive ,Nitric oxide ,Mice ,chemistry.chemical_compound ,In vivo ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Animals ,Nitric Oxide Donors ,Cytotoxicity ,Cisplatin ,Drug Synergism ,Dendritic Cells ,Combined Modality Therapy ,Enzyme Activation ,Mice, Inbred C57BL ,Sphingomyelin Phosphodiesterase ,Oncology ,chemistry ,Apoptosis ,Immunology ,Cancer research ,Female ,Acid sphingomyelinase ,Ex vivo ,Nitroso Compounds ,medicine.drug - Abstract
Cisplatin is one of the most effective anticancer drugs, but its severe toxic effects, including depletion of immune-competent cells, limit its efficacy. We combined the systemic treatment with cisplatin with intratumor delivery of dendritic cells (DC) previously treated ex vivo with a pulse of nitric oxide (NO) released by the NO donors (z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]-diazen-1-ium-1,2-diolate or isosorbide dinitrate. We found that this chemoimmunotherapy, tested in the B16 mouse model of melanoma, was significantly more efficacious than cisplatin alone, leading to tumor regression and animal survival at low doses of cisplatin that alone had no effect. Tumor cure was not observed when combining cisplatin with DCs not exposed to NO donors, indicating the key role of the pretreatment with NO. We investigated the mechanisms responsible for the synergic effect of NO-treated DCs and cisplatin and found that NO-treated DCs were protected both in vitro and in vivo from cisplatin-induced cytotoxicity. Cisplatin triggered DC apoptosis through increased expression and activation of acid sphingomyelinase; pretreatment of DCs with NO donors prevented such activation and inhibited activation of the downstream proapoptotic events, including generation of ceramide, activation of caspases 3 and 9, and mitochondrial depolarization. The effects of NO were mediated through generation of its physiologic messenger, cyclic GMP. We conclude that NO and NO generating drugs represent promising tools to increase the efficacy of chemoimmunotherapies in vivo, promoting the survival and increasing the function of injected cells by targeting a key pathway in cisplatin-induced cytotoxicity. [Cancer Res 2007;67(16):7559–64]
- Published
- 2007
12. Acid sphingomyelinase determines melanoma progression and metastatic behaviour via the microphtalmia-associated transcription factor signalling pathway
- Author
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C. De Palma, Fabio Pagni, C. Verdelli, Emma Assi, V. Russo, Fabio Simbari, A. Monno, Cristiana Perrotta, P.R. Querini, Emilio Clementi, Davide Cervia, Laura Bizzozero, Denise Cazzato, Bizzozero, L, Cazzato, D, Cervia, D, Assi, E, Simbari, F, Pagni, F, De Palma, C, Monno, A, Verdelli, C, Querini, P, Russo, V, Clementi, E, and Perrotta, C
- Subjects
Lung Neoplasms ,Melanoma, Experimental ,Down-Regulation ,Biology ,Mice ,Cell Movement ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Molecular Biology ,Transcription factor ,Melanoma ,Cell Proliferation ,Microphthalmia-Associated Transcription Factor ,Original Paper ,Cell growth ,Pigmentation ,Cyclin-dependent kinase 2 ,Cyclin-Dependent Kinase 2 ,Cancer ,Cell Biology ,Proto-Oncogene Proteins c-met ,medicine.disease ,Microphthalmia-associated transcription factor ,Mice, Inbred C57BL ,Sphingomyelin Phosphodiesterase ,Proto-Oncogene Proteins c-bcl-2 ,Cancer research ,biology.protein ,Disease Progression ,Female ,Signal transduction ,Acid sphingomyelinase ,medicine.drug ,Signal Transduction - Abstract
Melanoma is a rapidly growing and highly metastatic cancer with high mortality rates, for which a resolutive treatment is lacking. Identification of novel therapeutic strategies and biomarkers of tumour stage is thus of particular relevance. We report here on a novel biomarker and possible candidate therapeutic target, the sphingolipid metabolising enzyme acid sphingomyelinase (A-SMase). A-SMase expression correlates inversely with tumour stage in human melanoma biopsies. Studies in a mouse model of melanoma and on cell lines derived from mouse and human melanomas demonstrated that A-SMase levels of expression actually determine the malignant phenotype of melanoma cells in terms of pigmentation, tumour progression, invasiveness and metastatic ability. The action of A-SMase is mediated by the activation of the extracellular signal-regulated kinase, the subsequent proteasomal degradation of the Microphtalmia-associated transcription factor (Mitf) and inhibition of cyclin-dependent kinase 2, Bcl-2 and c-Met, downstream targets of Mitf involved in tumour cell proliferation, survival and metastatisation.
- Published
- 2013
13. Talniflumate abrogates mucin immune suppressive barrier improving efficacy of gemcitabine and nab-paclitaxel treatment in pancreatic cancer.
- Author
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Agostini A, Guerriero I, Piro G, Quero G, Roberto L, Esposito A, Caggiano A, Priori L, Scaglione G, De Sanctis F, Sistigu A, Musella M, Larghi A, Rizzatti G, Lucchetti D, Alfieri S, Sgambato A, Bria E, Bizzozero L, Arena S, Ugel S, Corbo V, Tortora G, and Carbone C
- Subjects
- Humans, Animals, Mice, Mucins, Gemcitabine, Pancreatic Intraductal Neoplasms, Pancreatic Neoplasms pathology, Carcinoma, Pancreatic Ductal pathology
- Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. This is due to its aggressive course, late diagnosis and its intrinsic drugs resistance. The complexity of the tumor, in terms of cell components and heterogeneity, has led to the approval of few therapies with limited efficacy. The study of the early stages of carcinogenesis provides the opportunity for the identification of actionable pathways that underpin therapeutic resistance., Methods: We analyzed 43 Intraductal papillary mucinous neoplasms (IPMN) (12 Low-grade and 31 High-grade) by Spatial Transcriptomics. Mouse and human pancreatic cancer organoids and T cells interaction platforms were established to test the role of mucins expression on T cells activity. Syngeneic mouse model of PDAC was used to explore the impact of mucins downregulation on standard therapy efficacy., Results: Spatial transcriptomics showed that mucin O-glycosylation pathway is increased in the progression from low-grade to high-grade IPMN. We identified GCNT3, a master regulator of mucins expression, as an actionable target of this pathway by talniflumate. We showed that talniflumate impaired mucins expression increasing T cell activation and recognition using both mouse and human organoid interaction platforms. In vivo experiments showed that talniflumate was able to increase the efficacy of the chemotherapy by boosting immune infiltration., Conclusions: Finally, we demonstrated that combination of talniflumate, an anti-inflammatory drug, with chemotherapy effectively improves anti-tumor effect in PDAC., (© 2023. The Author(s).)
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- 2023
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14. An Overview of the Molecular Cues and Their Intracellular Signaling Shared by Cancer and the Nervous System: From Neurotransmitters to Synaptic Proteins, Anatomy of an All-Inclusive Cooperation.
- Author
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Arese M, Bussolino F, Pergolizzi M, and Bizzozero L
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- Humans, Neurotransmitter Agents, Nervous System metabolism, Signal Transduction physiology, Neoplasms metabolism
- Abstract
We propose an overview of the molecular cues and their intracellular signaling involved in the crosstalk between cancer and the nervous system. While "cancer neuroscience" as a field is still in its infancy, the relation between cancer and the nervous system has been known for a long time, and a huge body of experimental data provides evidence that tumor-nervous system connections are widespread. They encompass different mechanisms at different tumor progression steps, are multifaceted, and display some intriguing analogies with the nervous system's physiological processes. Overall, we can say that many of the paradigmatic "hallmarks of cancer" depicted by Weinberg and Hanahan are affected by the nervous system in a variety of manners.
- Published
- 2022
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15. The neuronal protein Neuroligin 1 promotes colorectal cancer progression by modulating the APC/β-catenin pathway.
- Author
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Pergolizzi M, Bizzozero L, Maione F, Maldi E, Isella C, Macagno M, Mariella E, Bardelli A, Medico E, Marchiò C, Serini G, Di Nicolantonio F, Bussolino F, and Arese M
- Subjects
- Adenomatous Polyposis Coli Protein genetics, Adenomatous Polyposis Coli Protein metabolism, Animals, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Humans, Mice, Wnt Signaling Pathway, beta Catenin genetics, beta Catenin metabolism, Cell Adhesion Molecules, Neuronal genetics, Cell Adhesion Molecules, Neuronal metabolism, Colorectal Neoplasms pathology
- Abstract
Background: Colorectal cancer (CRC) remains largely incurable when diagnosed at the metastatic stage. Despite some advances in precision medicine for this disease in recent years, new molecular targets, as well as prognostic/predictive markers, are highly needed. Neuroligin 1 (NLGN1) is a transmembrane protein that interacts at the synapse with the tumor suppressor adenomatous polyposis Coli (APC), which is heavily involved in the pathogenesis of CRC and is a key player in the WNT/β-catenin pathway., Methods: After performing expression studies of NLGN1 on human CRC samples, in this paper we used in vitro and in vivo approaches to study CRC cells extravasation and metastasis formation capabilities. At the molecular level, the functional link between APC and NLGN1 in the cancer context was studied., Results: Here we show that NLGN1 is expressed in human colorectal tumors, including clusters of aggressive migrating (budding) single tumor cells and vascular emboli. We found that NLGN1 promotes CRC cells crossing of an endothelial monolayer (i.e. Trans-Endothelial Migration or TEM) in vitro, as well as cell extravasation/lung invasion and differential organ metastatization in two mouse models. Mechanistically, NLGN1 promotes APC localization to the cell membrane and co-immunoprecipitates with some isoforms of this protein stimulates β-catenin translocation to the nucleus, upregulates mesenchymal markers and WNT target genes and induces an "EMT phenotype" in CRC cell lines CONCLUSIONS: In conclusion, we have uncovered a novel modulator of CRC aggressiveness which impacts on a critical pathogenetic pathway of this disease, and may represent a novel therapeutic target, with the added benefit of carrying over substantial knowledge from the neurobiology field., (© 2022. The Author(s).)
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- 2022
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16. Tumoral Neuroligin 1 Promotes Cancer-Nerve Interactions and Synergizes with the Glial Cell Line-Derived Neurotrophic Factor.
- Author
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Bizzozero L, Pergolizzi M, Pascal D, Maldi E, Villari G, Erriquez J, Volante M, Serini G, Marchiò C, Bussolino F, and Arese M
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- Actin Depolymerizing Factors metabolism, Animals, Cell Line, Tumor, Cell Movement, Glial Cell Line-Derived Neurotrophic Factor Receptors metabolism, Mice, Inbred C57BL, Neoplasm Invasiveness, Neoplasms pathology, Nerve Tissue pathology, Protein Binding, Pseudopodia metabolism, Mice, Cell Adhesion Molecules, Neuronal metabolism, Glial Cell Line-Derived Neurotrophic Factor metabolism, Neoplasms metabolism, Nerve Tissue metabolism
- Abstract
Many nervous proteins are expressed in cancer cells. In this report, we asked whether the synaptic protein neuroligin 1 (NLGN1) was expressed by prostatic and pancreatic carcinomas; in addition, given the tendency of these tumors to interact with nerves, we asked whether NLGN1 played a role in this process. Through immunohistochemistry on human tissue microarrays, we showed that NLGN1 is expressed by prostatic and pancreatic cancer tissues in discrete stages and tumor districts. Next, we performed in vitro and in vivo assays, demonstrating that NLGN1 promotes cancer cell invasion and migration along nerves. Because of the established role of the neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) in tumor-nerve interactions, we assessed a potential NLGN1-GDNF cooperation. We found that blocking GDNF activity with a specific antibody completely inhibited NLGN1-induced in vitro cancer cell invasion of nerves. Finally, we demonstrated that, in the presence of NLGN1, GDNF markedly activates cofilin, a cytoskeletal regulatory protein, altering filopodia dynamics. In conclusion, our data further prove the existence of a molecular and functional cross-talk between the nervous system and cancer cells. NLGN1 was shown here to function along one of the most represented neurotrophic factors in the nerve microenvironment, possibly opening new therapeutic avenues.
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- 2022
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17. Modulation of Angiopoietin 2 release from endothelial cells and angiogenesis by the synaptic protein Neuroligin 2.
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Pergolizzi M, Bizzozero L, Riccitelli E, Pascal D, Samarelli AV, Bussolino F, and Arese M
- Subjects
- Animals, Cell Adhesion Molecules, Neuronal deficiency, Cell Adhesion Molecules, Neuronal genetics, Endothelial Cells metabolism, Endothelial Cells physiology, Humans, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Neovascularization, Pathologic, Nerve Tissue Proteins deficiency, Nerve Tissue Proteins genetics, Retinal Vessels cytology, Retinal Vessels physiology, Rho Guanine Nucleotide Exchange Factors physiology, Vascular Endothelial Growth Factor A physiology, Weibel-Palade Bodies physiology, von Willebrand Factor metabolism, Angiopoietin-2 metabolism, Cell Adhesion Molecules, Neuronal physiology, Neovascularization, Physiologic, Nerve Tissue Proteins physiology
- Abstract
The synaptic protein Neuroligin 2, similarly to its isoform Neuroligin 1, is produced by endothelial cells, but its activity in the vascular context remains unknown. This study aimed at verifying the hypothesis that Neuroligin 2, in parallel with its extraneuronal involvement in pancreatic beta cells exocytosis, modulated cytokine release from endothelial cells and consequently angiogenesis. We used in vitro approaches to modulate Neuroligin 2 expression and Neuroligin 2 null mice to test our hypotheses. In vitro, upon VEGF stimulation, Neuroligin 2 silencing strongly reduces Angiopoietin 2 release in the medium and increases the endothelial cell retention of Weibel Palade Bodies, the specialized organelles that store Angiopoietin 2 and various other cytokines. On the contrary, Neuroligin 2 overexpression almost depletes cells of Weibel Palade Bodies, independent of VEGF. In vivo, both the retina and tumor xenografts grown in NLGN2- null mice display an immature vasculature, with lower pericyte coverage and lower Tie2 phosphorylation. At the molecular level NLGN2 colocalizes with its neuronal partner collibystin, a CDC42 guanine nucleotide exchange factor, which is also expressed by endothelial cells and in turn modulates Angiopoietin 2 release. Neuroligin 2, an inhibitory synaptic protein, modulates a peculiar aspect of vascular function and could represent a novel target of therapy in various fields, from tumor angiogenesis to vascular diseases., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
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18. Tumor progression: the neuronal input.
- Author
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Arese M, Bussolino F, Pergolizzi M, Bizzozero L, and Pascal D
- Abstract
One of the challenges of cancer is its heterogeneity and rapid capacity to adapt. Notwithstanding significant progress in the last decades in genomics and precision medicine, new molecular targets and therapies appear highly necessary. One way to approach this complex problem is to consider cancer in the context of its cellular and molecular microenvironment, which includes nerves. The peripheral nerves, the topic of this review, modulate the biological behavior of the cancer cells and influence tumor progression, including the events related to the metastatic spread of the disease. This mechanism involves the release of neurotransmitters directly into the microenvironment and the activation of the corresponding membrane receptors. While this fact appears to complicate further the molecular landscape of cancer, the neurotransmitters are highly investigated molecules, and often are already targeted by well-developed drugs, a fact that can help finding new therapies at a fraction of the cost and time needed for new medicines (through the so-called drug repurposing). Moreover, the modulation of tumor progression by neurotransmitters can probably explain the long-recognized effects of psychological factors on the burden of cancer. We begin with an introduction on the tumor-nervous-connections and a description of the perineural invasion and neoneurogenesis, the two most important interaction patterns of cancer and nerves. Next, we discuss the most recent data that unequivocally demonstrate the necessity of the nervous system for tumor onset and growth. We introduce the molecular players of the tumor-nervous-connections by citing the role of three main families: neurotropic factors, axon guidance molecules, and neurotransmitters. Finally, we review the role the most important neurotransmitters in tumor biology and we conclude by analyzing the significance of the presented data for cancer therapy, with all the potential advantages and caveats., Competing Interests: Conflicts of Interest: The authors have no conflict of interest to declare.
- Published
- 2018
- Full Text
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19. Essential role for acid sphingomyelinase-inhibited autophagy in melanoma response to cisplatin.
- Author
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Cervia D, Assi E, De Palma C, Giovarelli M, Bizzozero L, Pambianco S, Di Renzo I, Zecchini S, Moscheni C, Vantaggiato C, Procacci P, Clementi E, and Perrotta C
- Subjects
- Animals, Drug Resistance, Neoplasm physiology, Humans, Melanoma pathology, Mice, TOR Serine-Threonine Kinases metabolism, Antineoplastic Agents pharmacology, Autophagy drug effects, Cisplatin pharmacology, Melanoma enzymology, Sphingomyelin Phosphodiesterase metabolism
- Abstract
The sphingolipid metabolising enzyme Acid Sphingomyelinase (A-SMase) has been recently shown to inhibit melanoma progression and correlate inversely to tumour grade. In this study we have investigated the role of A-SMase in the chemo-resistance to anticancer treatmentusing mice with melanoma allografts and melanoma cells differing in terms of expression/activity of A-SMase. Since autophagy is emerging as a key mechanism in tumour growth and chemo-resistance, we have also investigated whether an action of A-SMase in autophagy can explain its role. Melanoma sensitivity to chemotherapeutic agent cisplatin in terms of cell viability/apoptosis, tumour growth, and animal survival depended directly on the A-SMase levels in tumoural cells. A-SMase action was due to inhibition of autophagy through activation of Akt/mammalian target of rapamycin (mTOR) pathway. Treatment of melanoma-bearing mice with the autophagy inhibitor chloroquine restored sensitivity to cisplatin of tumours expressing low levels of A-SMase while no additive effects were observed in tumours characterised by sustained A-SMase levels. The fact that A-SMase in melanomas affects mTOR-regulated autophagy and plays a central role in cisplatin efficacy encourages pre-clinical testing on the modulation of A-SMase levels/activity as possible novel anti-neoplastic strategy., Competing Interests: The authors declare they have no known conflicts of interest in this work.
- Published
- 2016
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20. Modulation of Acid Sphingomyelinase in Melanoma Reprogrammes the Tumour Immune Microenvironment.
- Author
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Assi E, Cervia D, Bizzozero L, Capobianco A, Pambianco S, Morisi F, De Palma C, Moscheni C, Pellegrino P, Clementi E, and Perrotta C
- Subjects
- Animals, CD8-Positive T-Lymphocytes immunology, Cell Proliferation, Female, Immune Tolerance, Melanoma, Experimental pathology, Mice, Mice, Inbred C57BL, Cellular Reprogramming, Melanoma, Experimental immunology, Sphingomyelin Phosphodiesterase physiology, Tumor Microenvironment
- Abstract
The inflammatory microenvironment induces tumours to acquire an aggressive and immunosuppressive behaviour. Since acid sphingomyelinase (A-SMase) downregulation in melanoma was shown to determine a malignant phenotype, we aimed here to elucidate the role of A-SMase in the regulation of tumour immunogenic microenvironment using in vivo melanoma models in which A-SMase was either downregulated or maintained at constitutively high levels. We found high levels of inflammatory factors in low A-SMase expressing tumours, which also displayed an immunosuppressive/protumoural microenvironment: high levels of myeloid-derived suppressor cells (MDSCs) and regulatory T lymphocytes (Tregs), as well as low levels of dendritic cells (DCs). In contrast, the restoration of A-SMase in melanoma cells not only reduced tumour growth and immunosuppression, but also induced a high recruitment at tumour site of effector immune cells with an antitumoural function. Indeed, we observed a poor homing of MDSCs and Tregs and the increased recruitment of CD8(+) and CD4(+) T lymphocytes as well as the infiltration of DCs and CD8(+)/CD44(high) T lymphocytes. This study demonstrates that change of A-SMase expression in cancer cells is sufficient per se to tune in vivo melanoma growth and that A-SMase levels modulate immune cells at tumour site. This may be taken into consideration in the setting of therapeutic strategies.
- Published
- 2015
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21. Neuroligin 1 induces blood vessel maturation by cooperating with the α6 integrin.
- Author
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Samarelli AV, Riccitelli E, Bizzozero L, Silveira TN, Seano G, Pergolizzi M, Vitagliano G, Cascone I, Carpentier G, Bottos A, Primo L, Bussolino F, and Arese M
- Subjects
- Animals, Antigens, CD genetics, Antigens, CD metabolism, Cadherins genetics, Cadherins metabolism, Cell Adhesion physiology, Cell Adhesion Molecules, Neuronal genetics, Cell Movement physiology, Cell Proliferation, Endothelial Cells cytology, Human Umbilical Vein Endothelial Cells, Humans, Integrin alpha6 genetics, Mice, Mice, Mutant Strains, Retinal Vessels cytology, Cell Adhesion Molecules, Neuronal metabolism, Endothelial Cells metabolism, Integrin alpha6 metabolism, Neovascularization, Physiologic physiology, Retinal Vessels metabolism
- Abstract
The synaptic protein Neuroligin 1 (NLGN1), a cell adhesion molecule, is critical for the formation and consolidation of synaptic connectivity and is involved in vascular development. The mechanism through which NLGN1 acts, especially in vascular cells, is unknown. Here, we aimed at deepening our knowledge on the cellular activities and molecular pathways exploited by endothelial NLGN1 both in vitro and in vivo. We analyzed the phenotypic consequences of NLGN1 expression modulation in endothelial cells through in vitro angiogenesis assays and the mouse postnatal retinal angiogenesis model. We demonstrate that NLGN1, whereas not affecting endothelial cell proliferation or migration, modulates cell adhesion to the vessel stabilizing protein laminin through cooperation with the α6 integrin, a specific laminin receptor. Finally, we show that in vivo, NLGN1 and α6 integrin preferentially colocalize in the mature retinal vessels, whereas NLGN1 deletion causes an aberrant VE-cadherin, laminin and α6 integrin distribution in vessels, along with significant structural defects in the vascular tree., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Published
- 2014
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22. Acid sphingomyelinase determines melanoma progression and metastatic behaviour via the microphtalmia-associated transcription factor signalling pathway.
- Author
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Bizzozero L, Cazzato D, Cervia D, Assi E, Simbari F, Pagni F, De Palma C, Monno A, Verdelli C, Querini PR, Russo V, Clementi E, and Perrotta C
- Subjects
- Animals, Cell Line, Tumor, Cell Movement, Cell Proliferation, Cyclin-Dependent Kinase 2 metabolism, Disease Progression, Down-Regulation, Female, Humans, Lung Neoplasms pathology, Lung Neoplasms secondary, Melanoma metabolism, Melanoma, Experimental metabolism, Melanoma, Experimental mortality, Melanoma, Experimental pathology, Mice, Mice, Inbred C57BL, Pigmentation, Proto-Oncogene Proteins c-bcl-2 metabolism, Proto-Oncogene Proteins c-met metabolism, Sphingomyelin Phosphodiesterase antagonists & inhibitors, Sphingomyelin Phosphodiesterase genetics, Melanoma pathology, Microphthalmia-Associated Transcription Factor metabolism, Signal Transduction, Sphingomyelin Phosphodiesterase metabolism
- Abstract
Melanoma is a rapidly growing and highly metastatic cancer with high mortality rates, for which a resolutive treatment is lacking. Identification of novel therapeutic strategies and biomarkers of tumour stage is thus of particular relevance. We report here on a novel biomarker and possible candidate therapeutic target, the sphingolipid metabolising enzyme acid sphingomyelinase (A-SMase). A-SMase expression correlates inversely with tumour stage in human melanoma biopsies. Studies in a mouse model of melanoma and on cell lines derived from mouse and human melanomas demonstrated that A-SMase levels of expression actually determine the malignant phenotype of melanoma cells in terms of pigmentation, tumour progression, invasiveness and metastatic ability. The action of A-SMase is mediated by the activation of the extracellular signal-regulated kinase, the subsequent proteasomal degradation of the Microphtalmia-associated transcription factor (Mitf) and inhibition of cyclin-dependent kinase 2, Bcl-2 and c-Met, downstream targets of Mitf involved in tumour cell proliferation, survival and metastatisation.
- Published
- 2014
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23. Syntaxin 4 is required for acid sphingomyelinase activity and apoptotic function.
- Author
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Perrotta C, Bizzozero L, Cazzato D, Morlacchi S, Assi E, Simbari F, Zhang Y, Gulbins E, Bassi MT, Rosa P, and Clementi E
- Subjects
- Caspase 3 metabolism, Caspase 9 metabolism, Enzyme Activation physiology, Humans, Protein Transport physiology, Proto-Oncogene Proteins c-akt metabolism, Sphingomyelins metabolism, U937 Cells, Apoptosis physiology, Cell Membrane enzymology, Exocytosis physiology, Qa-SNARE Proteins metabolism, Sphingomyelin Phosphodiesterase metabolism, fas Receptor metabolism
- Abstract
Acid sphingomyelinase (A-SMase) is an important enzyme in sphingolipid metabolism and plays key roles in apoptosis, immunity, development, and cancer. In addition, it mediates cytotoxicity of cisplatin and some other chemotherapeutic drugs. The mechanism of A-SMase activation is still undefined. We now demonstrate that, upon CD95 stimulation, A-SMase is activated through translocation from intracellular compartments to the plasma membrane in an exocytic pathway requiring the t-SNARE protein syntaxin 4. Indeed, down-regulation of syntaxin 4 inhibits A-SMase translocation and activation induced by CD95 stimulation. This leads to inhibition of the CD95-triggered signaling events, including caspase 3 and 9 activation and apoptosis, activation of the survival pathway involving the protein kinase Akt, and important changes in cell cycle and proliferation. The molecular interaction between A-SMase and syntaxin 4 was not known and clarifies the mechanism of A-SMase activation. The novel actions of syntaxin 4 in sphingolipid metabolism and exocytosis we describe here define signaling mechanisms of broad relevance in cell pathophysiology.
- Published
- 2010
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24. Nitric oxide boosts chemoimmunotherapy via inhibition of acid sphingomyelinase in a mouse model of melanoma.
- Author
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Perrotta C, Bizzozero L, Falcone S, Rovere-Querini P, Prinetti A, Schuchman EH, Sonnino S, Manfredi AA, and Clementi E
- Subjects
- Animals, Cisplatin administration & dosage, Combined Modality Therapy, Drug Synergism, Enzyme Activation drug effects, Female, Isosorbide Dinitrate administration & dosage, Melanoma, Experimental drug therapy, Melanoma, Experimental enzymology, Melanoma, Experimental immunology, Mice, Mice, Inbred C57BL, Nitric Oxide Donors administration & dosage, Nitroso Compounds administration & dosage, Sphingomyelin Phosphodiesterase metabolism, Antineoplastic Combined Chemotherapy Protocols pharmacology, Dendritic Cells immunology, Immunotherapy, Adoptive methods, Melanoma, Experimental therapy, Sphingomyelin Phosphodiesterase antagonists & inhibitors
- Abstract
Cisplatin is one of the most effective anticancer drugs, but its severe toxic effects, including depletion of immune-competent cells, limit its efficacy. We combined the systemic treatment with cisplatin with intratumor delivery of dendritic cells (DC) previously treated ex vivo with a pulse of nitric oxide (NO) released by the NO donors (z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]-diazen-1-ium-1,2-diolate or isosorbide dinitrate. We found that this chemoimmunotherapy, tested in the B16 mouse model of melanoma, was significantly more efficacious than cisplatin alone, leading to tumor regression and animal survival at low doses of cisplatin that alone had no effect. Tumor cure was not observed when combining cisplatin with DCs not exposed to NO donors, indicating the key role of the pretreatment with NO. We investigated the mechanisms responsible for the synergic effect of NO-treated DCs and cisplatin and found that NO-treated DCs were protected both in vitro and in vivo from cisplatin-induced cytotoxicity. Cisplatin triggered DC apoptosis through increased expression and activation of acid sphingomyelinase; pretreatment of DCs with NO donors prevented such activation and inhibited activation of the downstream proapoptotic events, including generation of ceramide, activation of caspases 3 and 9, and mitochondrial depolarization. The effects of NO were mediated through generation of its physiologic messenger, cyclic GMP. We conclude that NO and NO generating drugs represent promising tools to increase the efficacy of chemoimmunotherapies in vivo, promoting the survival and increasing the function of injected cells by targeting a key pathway in cisplatin-induced cytotoxicity.
- Published
- 2007
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25. Transbasal approaches to aneurysms of the vertebro-basilar junction.
- Author
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Collice M, Arena O, D'Aliberti G, Bizzozero L, Fontana RA, Irace C, Todaro CA, Car PG, and Talamonti G
- Subjects
- Adult, Cerebral Angiography, Disabled Persons, Female, Humans, Intracranial Aneurysm diagnostic imaging, Middle Aged, Neurosurgery methods, Postoperative Complications mortality, Postoperative Complications surgery, Reoperation, Treatment Outcome, Basilar Artery, Intracranial Aneurysm surgery, Vertebral Artery
- Abstract
The most difficult aneurysms to be surgically treated are those of the vertebro-basilar junction area. This is due to their deep location and the proximity of brain stem and cranial nerves. Recently, new transbasal surgical approaches have been developed in order to realize a shorter and more direct access. Clival lesions, such as neoplasms, angiomas, and aneurysms, can now be safely faced through these routes. In this paper, we report our recent experience in transbasal approaches for the management of six consecutive patients, with aneurysms in this area. In four of these patients, the initial treatment consisted of an attempt at endovascular aneurysm obliteration using the Guglielmi Detachable Coil system, whereas, in the other two patients (basing on age, aneurysm size and neurological conditions), surgery was considered as the treatment of choice. Unfortunately, the endovascular treatment failed in all cases, and all patients had to be eventually operated on. In all cases, surgical clipping was performed through the combination of a transmastoid (asterional) approach with the suboccipital lateral approach. By this route, in all cases, parent arteries proved well delineated, the aneurysms could always be correctly clipped. Good long-term results were achieved in all cases but one. When surgery is to be performed, the importance of a thorough wide exposure of the whole vertebro-basilar junction area, as well as the importance of having multiple accesses to the lesion, cannot be overemphasized.
- Published
- 1998
26. Multidisciplinary (surgical and endovascular) approach to intracranial aneurysms.
- Author
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Collice M, D'Aliberti G, Arena O, Fontana RA, Bizzozero L, Solaini C, Villa F, Talamonti G, Levati A, Scialfa G, Boccardi E, and Branca V
- Subjects
- Aged, Aneurysm, Ruptured surgery, Aneurysm, Ruptured therapy, Glasgow Coma Scale, Humans, Intracranial Aneurysm physiopathology, Intracranial Aneurysm surgery, Middle Aged, Postoperative Complications, Retreatment, Retrospective Studies, Subarachnoid Hemorrhage surgery, Subarachnoid Hemorrhage therapy, Treatment Outcome, Embolization, Therapeutic methods, Intracranial Aneurysm therapy, Patient Care Team
- Abstract
In spite of the availability of the new endovascular technique (GDC) to manage cerebral aneurysms, to date, the crucial question "which is the proper treatment in a given patient?" still remains unsettled. In order to check whether an answer is possible, we retrospectively reviewed a personal series of 192 consecutive patients with cerebral aneurysms (1993-1995). We found 164 patients who had been considered eligible for active aneurysm treatment. Treatment modality has been chosen case by case on the basis of patient conditions, and aneurysm size and location. Four groups of patients were identified: Group 1: 104 patients (63.4%) with subarachnoid hemorrhage (SAH) in whom the treatment of choice was surgery; Group 2: 27 SAH patients (16.4%) in whom the first choice was GDC; Group 3: 7 SAH patients (4.2%) who died before the scheduled treatment; Group 4: 26 patients (15%) with not ruptured aneurysm who had either surgery or GDC. Based on the results of this series (improvement of the overall results through the multidisciplinary approach), we have developed the guidelines to prospectively manage future cases of cerebral aneurysms with the purpose to rationalize the management, thus further improving the overall results.
- Published
- 1998
27. Comparison of pediatric and adult cerebral arteriovenous malformations.
- Author
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D'Aliberti G, Talamonti G, Versari PP, Todaro C, Bizzozero L, Arena O, and Collice M
- Subjects
- Adolescent, Adult, Aged, Cerebral Hemorrhage etiology, Child, Combined Modality Therapy, Embolization, Therapeutic, Female, Humans, Intracranial Arteriovenous Malformations diagnostic imaging, Male, Middle Aged, Radiography, Radiosurgery, Retrospective Studies, Seizures etiology, Treatment Outcome, Intracranial Arteriovenous Malformations physiopathology, Intracranial Arteriovenous Malformations therapy
- Abstract
The authors report 19 consecutive children with cerebral arteriovenous malformations over the period 1978-1992. These patients are compared with a series of 120 consecutive adult patients with the same pathology, managed during the same period. The main clinical and angiographic features, as well as the treatment modalities and outcome are reviewed and compared. Children seem to harbour smaller and simpler lesions than adults. Furthermore, despite a more severe clinical presentation, children appears to fare better than adults. The possibility of evolution of brain arteriovenous malformations is discussed.
- Published
- 1997
28. Cavernous hemangioma of the skull. Case report and review of the literature.
- Author
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Bizzozero L, Solaining Talamonti C, Villa F, Brusamolino R, and Collice M
- Subjects
- Adult, Blood Vessels pathology, Hemangioma, Cavernous blood supply, Hemangioma, Cavernous pathology, Humans, Male, Skull Neoplasms blood supply, Skull Neoplasms pathology, Hemangioma, Cavernous diagnosis, Hemangioma, Cavernous surgery, Skull Neoplasms diagnosis, Skull Neoplasms surgery
- Abstract
Osseous hemangiomas are rare skeletal tumors that constitute 0.7% of all osseous neoplasms. The most common site is the vertebral column while involvement of the calvarium is extremely rare accounting for 0.2% of all bone neoplasm. The authors present a case of a 35-years-old man who was admitted with right parietal swelling and review the gross appearance, pathogenesis, histopathology, radiological features and treatment of this neoplasm.
- Published
- 1997
29. Tumour suppressor genes, immunology and local manifestations of neurofibromatosis phenotypes.
- Author
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Gerosa PL, Spinelli M, Iannarelli S, Giussani G, Canepari C, Fontana A, Vai C, and Bizzozero L
- Subjects
- Adolescent, Adult, Aged, Biopsy, Child, Female, Humans, Male, Middle Aged, Neurofibromatosis 1 pathology, Neurofibromatosis 2 pathology, Phenotype, Genes, Tumor Suppressor, Neurofibromatosis 1 genetics, Neurofibromatosis 1 immunology, Neurofibromatosis 2 genetics, Neurofibromatosis 2 immunology
- Abstract
Research on Neurofibromatosis (NF) has been directed at understanding what determines disease quiescence, exacerbation, and the possible malignant evolution. Studies on NF have examined the role of genetic oncosuppression in the evolution of the defence against the non-self. Paraffin fixed specimens of benign and malignant neoplasia, occurring in patients with NF1 and NF2, were tested for the presence of p53: a reliable marker of genetic oncosupression. The wild type variant of p53 is expressed in malignant neoplasia, and is usually not expressed in benign tumors. Contrariwise, an immune reaction it is seen in benign tumors and is practically absent in malignant tumors. Evidence of protein p53 in the various malignant neoplasias studied by our group seems to reflect the up-regulation on the oncosuppresive genetic potential that occurs while there is a lack of immunological defence. In the presence of an immunological defence, the expression p53 is normally not seen e.g. plexiform neurofibromas. The evolution of the various neoplastic types here reported was the same as that reported by current clinical and experimental models: the cell's defective genes are no longer suppressed and after activation the genes undergo initiation, promotion, and the cell sustains inflammatory-immune reactions that lead to fibrosis; what follows is a variable period of apparent quiescence. Severe pathogenic stimuli may act on predisposed cells and deteriorate pre-existing genetic damage, casting the cell into a phase of dysplastic or neoplastic proliferation that overcomes the body's defences. Hope for future therapy lies in the development of drugs that can either mimic the immune system or the proteins encoded by the oncosuppressor genes.
- Published
- 1996
30. "High risk" anterior basal skull fractures. Surgical treatment of 64 consecutive cases.
- Author
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Talamonti G, Fontana R, Villa F, D'Aliberti G, Arena O, Bizzozero L, Versari P, and Collice M
- Subjects
- Aged, Craniocerebral Trauma diagnostic imaging, Humans, Middle Aged, Risk Factors, Skull Fractures diagnostic imaging, Tomography, X-Ray Computed, Craniocerebral Trauma surgery, Skull Fractures surgery
- Abstract
Anterior Basal Skull Fractures (ABSFs) may be complicated by Cerebrospinal Fluid (CSF) fistulae and intracranial infections. An initially non-operative management is usually suggested since most fistulae spontaneously stop within a few days thus requiring no surgical repair. However, if the fistula fails to stop or recurs, surgical treatment is to be considered. Furthermore, if the fracture is complicated by meningitis, there is a relative risk of recurring infections and surgical repair may be also considered. Finally, surgical repair may be suggested in cases of compound, comminuted, depressed, largely extended cranio-facial fractures (the so-called "fracas craniofaciaux") where spontaneous healing is considered unlikely and risk of infection is high. Accordingly we termed "high risk" fractures those associated with active (persistent or recurring) cerebrospinal fluid fistula, those with meningitis and the so-called "fracas craniofaciaux". In this paper, we report our personal experience in surgical treatment of 64 consecutive "high risk" anterior basal skull fractures. Thirty-seven patients had persistent or recurring fistulae, ten had intracranial infections and seventeen had severe bone derangement of the anterior skull base. The osteodural repairs were performed through bilateral or unilateral subfrontal approach. In 59 cases the initial procedure was successful whereas 4 patient needed additional surgery but were ultimately successfully treated. One patient died. No major permanent neurologic or neuropsychologic impairments were reported. On the basis of our experience, we think that intracranial repair is a very suitable treatment modality in facing "high risk" anterior basal skull fractures.
- Published
- 1995
31. Intramedullary spinal cord metastasis. Case report.
- Author
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Bizzozero L, Ferrara M, Villa F, Fontana R, Brusamolino R, and Collice M
- Subjects
- Adenocarcinoma diagnosis, Animals, Breast Neoplasms diagnosis, Female, Follow-Up Studies, Gadolinium, Humans, Magnetic Resonance Imaging methods, Middle Aged, Pituitary Gland pathology, Pituitary Neoplasms pathology, Pituitary Neoplasms secondary, Spinal Cord Neoplasms diagnosis, Adenocarcinoma pathology, Breast Neoplasms pathology, Spinal Cord Neoplasms secondary
- Abstract
The authors report a case of intramedullary spinal cord tumor in a 52-years old woman operated, 5 years before the beginning of medullary syndrome, for mammary carcinoma. Intramedullary metastasis was associated to another secondary localization in the pituitary stalk. The importance of magnetic resonance image and aggressive treatment is stressed.
- Published
- 1994
32. [The clinico-immunological surveillance of neurofibromatosis].
- Author
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Gerosa P, Vai C, Canepari C, Fontana A, Bizzozero L, Giussani G, and Spinelli M
- Subjects
- Adolescent, Adult, Biomarkers blood, Child, Diseases in Twins, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neurofibromatosis 1 epidemiology, Twins, Dizygotic, Neurofibromatosis 1 immunology, Population Surveillance
- Abstract
Considering the more recent physiopathogenetic advancements in neurofibromatosis (NF), we propose to employ novel instrumental and laboratory procedures for the immunological and clinical surveillance of NF. In NF the evolution of the non-self can lead to disease expansion, at times transforming into malignancy. Contemporarily, the resulting immunological reactivity can either lead to the type of fibrosis that one sees in paraneoplastic connective tissue disease or be deficient. Through interdisciplinary biohumoral analyses were carried out contemporarily so as to gain comparative insight into the eventual unfolding of immunological and fibrotic phenomena. The range of the clinical follow-up varied from one to four years with periodic day hospital admissions. We studied ten NF patients that originated from southern Italy and belonged to middle and lower middle class status; we also studied one healthy subject who had the same HLA haplotype as his NF affected twin. We performed biohumoral analyses in clinical stable patients and saw moderate variations in induces useful for monitoring the evolution of this dysplastic-neoplastic condition, e.g. procollagens, interleukin-2, NSE (assayed with radioimmunological methods) and complement these parameters proved to be of use in monitoring the fibrotic evolution of NF. The intent of our work was to complete the earlier studies on NF surveillance, especially during periods of disease evolution and immuno-fibrotic alteration.
- Published
- 1994
33. Inflammatory meningioma of the fourth ventricle. Case report.
- Author
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Ferrara M, Bizzozero L, D'Aliberti G, Fontana R, Branca V, Barberis M, and Brusamolino R
- Subjects
- Adult, Cerebral Ventricle Neoplasms pathology, Humans, Magnetic Resonance Imaging, Male, Meningeal Neoplasms pathology, Meningioma pathology, Cerebral Ventricle Neoplasms diagnosis, Cerebral Ventricle Neoplasms surgery, Meningeal Neoplasms diagnosis, Meningeal Neoplasms surgery, Meningioma diagnosis, Meningioma surgery
- Abstract
A case of meningioma with inflammatory reaction within the fourth ventricle in a 37 year-old man is described. The differential diagnosis between inflammatory meningioma, plasma cell granuloma and a possible collision of a meningioma with a plasmacytoma is discussed. The immunohistochemical examination of plasma cell population is emphasized. This is the first case reported of inflammatory meningioma located in the fourth ventricle.
- Published
- 1994
34. Immunological and clinical surveillance in Recklinghausen's neurofibromatosis (NF1).
- Author
-
Gerosa PL, Vai C, Bizzozero L, Fontana A, Giussani G, and Spinelli M
- Subjects
- Adolescent, Adult, Aged, Antigen-Antibody Complex blood, Complement C3 metabolism, Female, Humans, Immune System physiopathology, Immunoglobulins blood, Leukocyte Count, Male, Middle Aged, Neurofibromatosis 1 blood, Neurofibromatosis 1 immunology
- Abstract
Neurofibromatosis evolution is described in relation to the factors that may favour its expansion and immune modifications. NF1 monitorization should employ periodic clinical and immune surveillance. Such an approach would allow the application of immunomodulating treatment (e.g. adapted therapy) only when indicated, thereby reducing its duration and potentiating its efficacy.
- Published
- 1993
35. [Local immune response in neurofibromatosis type 1 and type 2].
- Author
-
Gerosa PL, Vai C, Bizzozero L, Fontana A, Giussani G, and Spinelli M
- Subjects
- Adolescent, Adult, Aged, Child, Female, Humans, Immunoglobulin G metabolism, Immunoglobulin M metabolism, Male, Middle Aged, Neurofibromatosis 1 metabolism, Neurofibromatosis 1 pathology, Neurofibromatosis 2 metabolism, Neurofibromatosis 2 pathology, S100 Proteins metabolism, Neurofibromatosis 1 immunology, Neurofibromatosis 2 immunology
- Abstract
Neurofibromatosis, in all its variant forms, is a hereditary disease characterized by dysplasia, neoplasia, and the tendency to expand and undergo malignant transformation. We underline the presence of chronic inflammation and of immunologic interdependency. The immune reactions against the non-self have been investigated histologically in light of the concepts of immunosurveillance and immunotolerance. Such investigations would ameliorate subsequent studies and favour the employment of immunomodulatory treatments.
- Published
- 1993
36. Head-injured patients who talk and deteriorate.
- Author
-
Talamonti G, Fontana RA, Bizzozero L, Versari P, and Collice M
- Subjects
- Glasgow Coma Scale, Humans, Prognosis, Referral and Consultation, Time Factors, Tomography, X-Ray Computed, Consciousness physiology, Craniocerebral Trauma physiopathology
- Published
- 1992
- Full Text
- View/download PDF
37. Cerebral metastasis from an epithelioid malignant schwannoma: case report.
- Author
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D'Angelo V, Casadei G, and Bizzozero L
- Subjects
- Aged, Brain Neoplasms pathology, Epithelium, Female, Humans, Neurilemmoma pathology, Brain Neoplasms secondary, Neurilemmoma secondary, Peripheral Nervous System Neoplasms pathology
- Abstract
The authors present a case of brain metastasis from an epithelioid malignant schwannoma. The patient previously had undergone a surgical resection of the primary tumor in the right forearm. The neoplasm was composed of nests of cells with an entirely epithelioid appearance without spindle cell areas. Immunohistochemically, the tumor cells stained positive for S100 protein and negative for cytokeratin, neuron-specific enolase, and anti-melanoma antiserum. To our knowledge, this is the first reported case of cerebral metastasis from an epithelioid malignant tumor of the peripheral nerve sheath.
- Published
- 1991
- Full Text
- View/download PDF
38. [Immune reaction in von Recklinghausen's neurofibromatosis].
- Author
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Gerosa PL, Bizzozero L, Fontana A, Giussani G, Spinelli M, and Vai C
- Subjects
- Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Neurofibromatosis 1 blood, Neurofibromatosis 1 immunology
- Abstract
A multidisciplinary study was performed on cases of neurofibromatosis to highlight the immunological reaction using broad-spectrum hematic tests and multiphase evaluation together with clinical and instrumental monitoring. The aim of the study was to focus attention on this rare disease and prompt further sequential immunological studies. A greater knowledge of the disease would allow the promising potential of new drugs to be exploited, in particular selective immunomodulatory drugs, in the hope of controlling the symptoms of disease (and overcoming further obstacles to the surgical removal of any neurofibromas that the patient wishes.
- Published
- 1991
39. Value of magnetic resonance imaging in spontaneous extradural spinal hematoma due to vascular malformation: case report.
- Author
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D'Angelo V, Bizzozero L, Talamonti G, Ferrara M, and Colombo N
- Subjects
- Arteriovenous Malformations surgery, Hematoma, Epidural, Cranial complications, Hematoma, Epidural, Cranial etiology, Hematoma, Epidural, Cranial surgery, Humans, Laminectomy, Magnetic Resonance Imaging, Male, Middle Aged, Spinal Cord pathology, Spinal Cord surgery, Spinal Cord Compression etiology, Spinal Cord Compression surgery, Arteriovenous Malformations complications, Hematoma, Epidural, Cranial diagnosis, Spinal Cord blood supply, Spinal Cord Compression diagnosis
- Abstract
A case of spinal cord compression due to spontaneous extradural spinal hematoma is reported. A spinal arteriovenous malformation was suspected on the basis of magnetic resonance imaging. Early surgical exploration allowed a complete neurological recovery. The vascular malformation was histopathologically confirmed. The role of magnetic resonance imaging in the evaluation of acute spinal cord compression syndromes is stressed.
- Published
- 1990
- Full Text
- View/download PDF
40. Late malignant recurrence of childhood cerebellar astrocytoma.
- Author
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Casadei GP, Arrigoni GL, D'Angelo V, and Bizzozero L
- Subjects
- Adolescent, Adult, Astrocytes pathology, Astrocytoma surgery, Brain Stem pathology, Cerebellar Neoplasms surgery, Cerebellum pathology, Cerebral Ventricles pathology, Child, Female, Follow-Up Studies, Humans, Neoplasm Recurrence, Local surgery, Reoperation, Astrocytoma pathology, Cerebellar Neoplasms pathology, Neoplasm Recurrence, Local pathology
- Abstract
Juvenile pilocytic astrocytoma of the cerebellum has a benign course and a good prognosis. We report a case of juvenile cerebellar astrocytoma in a 6-year-old girl that underwent surgical resection of the tumor and had two recurrences, 13 and 35 years after first removal. After surgery the patient did not receive any radiation therapy. The last relapse showed histological features of an anaplastic astrocytoma. Six months later the patient died with a diffuse leptomeningeal dissemination. Late malignant transformation of a benign cerebellar astrocytoma is very rare and it is thought to be favored by postsurgical irradiation. The possible pathogenetic mechanisms of this evolution are discussed. This case and the few others reported in the literature emphasize the risk of an unpredictable outcome with the low-grade cerebellar astrocytomas of childhood.
- Published
- 1990
41. Chronic subdural hematoma associated with dural metastasis from mammary carcinoma. Case report and review of the literature.
- Author
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D'Angelo V, Bizzozero L, Fontana RA, Colombo N, and Minola E
- Subjects
- Aged, Brain Neoplasms complications, Female, Humans, Brain Neoplasms secondary, Breast Neoplasms, Dura Mater, Hematoma, Subdural etiology
- Published
- 1988
42. "Primary" leptomeningeal dissemination of medulloblastoma. Report of an unusual case.
- Author
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Ferrara M, Bizzozero L, Fiumara E, D'Angelo V, Corona C, and Colombo N
- Subjects
- Brain Neoplasms surgery, Child, Preschool, Humans, Male, Medulloblastoma diagnostic imaging, Medulloblastoma surgery, Meningeal Neoplasms diagnostic imaging, Meningeal Neoplasms surgery, Tomography, X-Ray Computed, Brain Neoplasms diagnostic imaging, Medulloblastoma secondary, Meningeal Neoplasms secondary
- Abstract
The Authors report the case of a 5-year-old boy medulloblastoma presenting with "primary" widespread diffusion in the subarachnoid spaces of the posterior fossa without true mass lesion. The diagnosis, suspected first on the basis of the computed tomography (CT) findings, was confirmed by cytological examination of the cerebrospinal fluid (CSF) and by surgery. The Authors analyse the peculiar clinical features (rapid and severe deterioration of general conditions, hyperacute course of the illness and fatal issue) and the morphological aspects of the tumor (CT and surgical findings). To our knowledge no case of "primary" dissemination of medulloblastoma was previously reported.
- Published
- 1989
43. Intraventricular craniopharyngioma. Clinical and surgical considerations.
- Author
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Ferrara M, Bizzozero L, D'Angelo V, Corona C, and Fiumara E
- Subjects
- Adult, Cerebral Ventricle Neoplasms diagnostic imaging, Craniopharyngioma diagnostic imaging, Female, Humans, Male, Middle Aged, Tomography, X-Ray Computed, Cerebral Ventricle Neoplasms surgery, Craniopharyngioma surgery
- Abstract
The authors present two cases of craniopharyngioma wholly located within the cavity of the third ventricle. The rarity of this condition is outlined. In these cases the computed tomography is not always sufficient to determine the correct surgical approach; therefore the Authors stress the importance of the clinical findings.
- Published
- 1989
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