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2. Author Correction: Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B

Author

Musella, Martina, Guarracino, Andrea, Manduca, Nicoletta, Galassi, Claudia, Ruggiero, Eliana, Potenza, Alessia, Maccafeo, Ester, Manic, Gwenola, Mattiello, Luca, Soliman Abdel Rehim, Sara, Signore, Michele, Pietrosanto, Marco, Helmer-Citterich, Manuela, Pallocca, Matteo, Fanciulli, Maurizio, Bruno, Tiziana, De Nicola, Francesca, Corleone, Giacomo, Di Benedetto, Anna, Ercolani, Cristiana, Pescarmona, Edoardo, Pizzuti, Laura, Guidi, Francesco, Sperati, Francesca, Vitale, Sara, Macchia, Daniele, Spada, Massimo, Schiavoni, Giovanna, Mattei, Fabrizio, De Ninno, Adele, Businaro, Luca, Lucarini, Valeria, Bracci, Laura, Aricò, Eleonora, Ziccheddu, Giovanna, Facchiano, Francesco, Rossi, Stefania, Sanchez, Massimo, Boe, Alessandra, Biffoni, Mauro, De Maria, Ruggero, Vitale, Ilio, and Sistigu, Antonella

Published
2024
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3. Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B

Author

Musella, Martina, Guarracino, Andrea, Manduca, Nicoletta, Galassi, Claudia, Ruggiero, Eliana, Potenza, Alessia, Maccafeo, Ester, Manic, Gwenola, Mattiello, Luca, Soliman Abdel Rehim, Sara, Signore, Michele, Pietrosanto, Marco, Helmer-Citterich, Manuela, Pallocca, Matteo, Fanciulli, Maurizio, Bruno, Tiziana, De Nicola, Francesca, Corleone, Giacomo, Di Benedetto, Anna, Ercolani, Cristiana, Pescarmona, Edoardo, Pizzuti, Laura, Guidi, Francesco, Sperati, Francesca, Vitale, Sara, Macchia, Daniele, Spada, Massimo, Schiavoni, Giovanna, Mattei, Fabrizio, De Ninno, Adele, Businaro, Luca, Lucarini, Valeria, Bracci, Laura, Aricò, Eleonora, Ziccheddu, Giovanna, Facchiano, Francesco, Rossi, Stefania, Sanchez, Massimo, Boe, Alessandra, Biffoni, Mauro, De Maria, Ruggero, Vitale, Ilio, and Sistigu, Antonella

Published
2022
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6. Antiviral and immunomodulatory interferon-beta in high-risk COVID-19 patients: a structured summary of a study protocol for a randomised controlled trial

Author

Aricò, Eleonora, Castiello, Luciano, Bracci, Laura, Urbani, Francesca, Lombardo, Flavia, Bacigalupo, Ilaria, Ancidoni, Antonio, Vanacore, Nicola, Falcione, Alessandro, Reggiani, Chiara, Dutti, Giovanni Marco, Maglie, Maria Grazia, Papa, Ombretta, Bartoletti, Pier Luigi, Ozzella, Giuseppina, Bevilacqua, Nazario, Nicastri, Emanuele, Belardelli, Filippo, and Sconocchia, Giuseppe

Published
2021
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10. Supplementary Figure 1 from Disruption of IFN-I Signaling Promotes HER2/Neu Tumor Progression and Breast Cancer Stem Cells

Author

Castiello, Luciano, primary, Sestili, Paola, primary, Schiavoni, Giovanna, primary, Dattilo, Rosanna, primary, Monque, Domenica M., primary, Ciaffoni, Fiorella, primary, Iezzi, Manuela, primary, Lamolinara, Alessia, primary, Sistigu, Antonella, primary, Moschella, Federica, primary, Pacca, Anna Maria, primary, Macchia, Daniele, primary, Ferrantini, Maria, primary, Zeuner, Ann, primary, Biffoni, Mauro, primary, Proietti, Enrico, primary, Belardelli, Filippo, primary, and Aricò, Eleonora, primary

Published
2023
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11. Supplementary Table 1 from Disruption of IFN-I Signaling Promotes HER2/Neu Tumor Progression and Breast Cancer Stem Cells

Author

Castiello, Luciano, primary, Sestili, Paola, primary, Schiavoni, Giovanna, primary, Dattilo, Rosanna, primary, Monque, Domenica M., primary, Ciaffoni, Fiorella, primary, Iezzi, Manuela, primary, Lamolinara, Alessia, primary, Sistigu, Antonella, primary, Moschella, Federica, primary, Pacca, Anna Maria, primary, Macchia, Daniele, primary, Ferrantini, Maria, primary, Zeuner, Ann, primary, Biffoni, Mauro, primary, Proietti, Enrico, primary, Belardelli, Filippo, primary, and Aricò, Eleonora, primary

Published
2023
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12. Data from Disruption of IFN-I Signaling Promotes HER2/Neu Tumor Progression and Breast Cancer Stem Cells

Author

Castiello, Luciano, primary, Sestili, Paola, primary, Schiavoni, Giovanna, primary, Dattilo, Rosanna, primary, Monque, Domenica M., primary, Ciaffoni, Fiorella, primary, Iezzi, Manuela, primary, Lamolinara, Alessia, primary, Sistigu, Antonella, primary, Moschella, Federica, primary, Pacca, Anna Maria, primary, Macchia, Daniele, primary, Ferrantini, Maria, primary, Zeuner, Ann, primary, Biffoni, Mauro, primary, Proietti, Enrico, primary, Belardelli, Filippo, primary, and Aricò, Eleonora, primary

Published
2023
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13. Supplementary Figure 2 from Disruption of IFN-I Signaling Promotes HER2/Neu Tumor Progression and Breast Cancer Stem Cells

Author

Castiello, Luciano, primary, Sestili, Paola, primary, Schiavoni, Giovanna, primary, Dattilo, Rosanna, primary, Monque, Domenica M., primary, Ciaffoni, Fiorella, primary, Iezzi, Manuela, primary, Lamolinara, Alessia, primary, Sistigu, Antonella, primary, Moschella, Federica, primary, Pacca, Anna Maria, primary, Macchia, Daniele, primary, Ferrantini, Maria, primary, Zeuner, Ann, primary, Biffoni, Mauro, primary, Proietti, Enrico, primary, Belardelli, Filippo, primary, and Aricò, Eleonora, primary

Published
2023
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14. Supplementary figures legend from Disruption of IFN-I Signaling Promotes HER2/Neu Tumor Progression and Breast Cancer Stem Cells

Author

Castiello, Luciano, primary, Sestili, Paola, primary, Schiavoni, Giovanna, primary, Dattilo, Rosanna, primary, Monque, Domenica M., primary, Ciaffoni, Fiorella, primary, Iezzi, Manuela, primary, Lamolinara, Alessia, primary, Sistigu, Antonella, primary, Moschella, Federica, primary, Pacca, Anna Maria, primary, Macchia, Daniele, primary, Ferrantini, Maria, primary, Zeuner, Ann, primary, Biffoni, Mauro, primary, Proietti, Enrico, primary, Belardelli, Filippo, primary, and Aricò, Eleonora, primary

Published
2023
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15. Supplementary Figure 3 from Disruption of IFN-I Signaling Promotes HER2/Neu Tumor Progression and Breast Cancer Stem Cells

Author

Castiello, Luciano, primary, Sestili, Paola, primary, Schiavoni, Giovanna, primary, Dattilo, Rosanna, primary, Monque, Domenica M., primary, Ciaffoni, Fiorella, primary, Iezzi, Manuela, primary, Lamolinara, Alessia, primary, Sistigu, Antonella, primary, Moschella, Federica, primary, Pacca, Anna Maria, primary, Macchia, Daniele, primary, Ferrantini, Maria, primary, Zeuner, Ann, primary, Biffoni, Mauro, primary, Proietti, Enrico, primary, Belardelli, Filippo, primary, and Aricò, Eleonora, primary

Published
2023
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16. Supplementary Figure 1 from Clinical and Antitumor Immune Responses in Relapsed/Refractory Follicular Lymphoma Patients after Intranodal Injections of IFNα-Dendritic Cells and Rituximab: a Phase I Clinical Trial

Author

Cox, M. Christina, primary, Castiello, Luciano, primary, Mattei, Mauro, primary, Santodonato, Laura, primary, D'Agostino, Giuseppina, primary, Muraro, Elena, primary, Martorelli, Debora, primary, Lapenta, Caterina, primary, Di Napoli, Arianna, primary, Di Landro, Francesca, primary, Cangemi, Michela, primary, Pavan, Antonio, primary, Castaldo, Paolo, primary, Hohaus, Stefan, primary, Donati, Simona, primary, Montefiore, Enrica, primary, Berdini, Cinzia, primary, Carlei, Davide, primary, Monque, Domenica M., primary, Ruco, Luigi, primary, Prosperi, Daniela, primary, Tafuri, Agostino, primary, Spadaro, Francesca, primary, Sestili, Paola, primary, Spada, Massimo, primary, Dolcetti, Riccardo, primary, Santini, Stefano M., primary, Rozera, Carmela, primary, Aricò, Eleonora, primary, Capone, Imerio, primary, and Belardelli, Filippo, primary

Published
2023
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17. Supplementary Figure 2 from Clinical and Antitumor Immune Responses in Relapsed/Refractory Follicular Lymphoma Patients after Intranodal Injections of IFNα-Dendritic Cells and Rituximab: a Phase I Clinical Trial

Author

Cox, M. Christina, primary, Castiello, Luciano, primary, Mattei, Mauro, primary, Santodonato, Laura, primary, D'Agostino, Giuseppina, primary, Muraro, Elena, primary, Martorelli, Debora, primary, Lapenta, Caterina, primary, Di Napoli, Arianna, primary, Di Landro, Francesca, primary, Cangemi, Michela, primary, Pavan, Antonio, primary, Castaldo, Paolo, primary, Hohaus, Stefan, primary, Donati, Simona, primary, Montefiore, Enrica, primary, Berdini, Cinzia, primary, Carlei, Davide, primary, Monque, Domenica M., primary, Ruco, Luigi, primary, Prosperi, Daniela, primary, Tafuri, Agostino, primary, Spadaro, Francesca, primary, Sestili, Paola, primary, Spada, Massimo, primary, Dolcetti, Riccardo, primary, Santini, Stefano M., primary, Rozera, Carmela, primary, Aricò, Eleonora, primary, Capone, Imerio, primary, and Belardelli, Filippo, primary

Published
2023
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18. Supplementary Tables from Clinical and Antitumor Immune Responses in Relapsed/Refractory Follicular Lymphoma Patients after Intranodal Injections of IFNα-Dendritic Cells and Rituximab: a Phase I Clinical Trial

Author

Cox, M. Christina, primary, Castiello, Luciano, primary, Mattei, Mauro, primary, Santodonato, Laura, primary, D'Agostino, Giuseppina, primary, Muraro, Elena, primary, Martorelli, Debora, primary, Lapenta, Caterina, primary, Di Napoli, Arianna, primary, Di Landro, Francesca, primary, Cangemi, Michela, primary, Pavan, Antonio, primary, Castaldo, Paolo, primary, Hohaus, Stefan, primary, Donati, Simona, primary, Montefiore, Enrica, primary, Berdini, Cinzia, primary, Carlei, Davide, primary, Monque, Domenica M., primary, Ruco, Luigi, primary, Prosperi, Daniela, primary, Tafuri, Agostino, primary, Spadaro, Francesca, primary, Sestili, Paola, primary, Spada, Massimo, primary, Dolcetti, Riccardo, primary, Santini, Stefano M., primary, Rozera, Carmela, primary, Aricò, Eleonora, primary, Capone, Imerio, primary, and Belardelli, Filippo, primary

Published
2023
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29. Chronic Isolation Stress Affects Central Neuroendocrine Signaling Leading to a Metabolically Active Microenvironment in a Mouse Model of Breast Cancer

Author

Berry, Alessandra, primary, Collacchi, Barbara, additional, Capoccia, Sara, additional, D'Urso, Maria Teresa, additional, Cecchetti, Serena, additional, Raggi, Carla, additional, Sestili, Paola, additional, Aricò, Eleonora, additional, Pontecorvi, Giada, additional, Puglisi, Rossella, additional, Ortona, Elena, additional, and Cirulli, Francesca, additional

Published
2021
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30. Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B

Author

Sistigu, Antonella, primary, Musella, Martina, additional, Galassi, Claudia, additional, Guarracino, Andrea, additional, Manic, Gwenola, additional, Manduca, Nicoletta, additional, Pietrosanto, Marco, additional, Helmer-Citterich, Manuela, additional, Pallocca, Matteo, additional, Fanciulli, Maurizio, additional, Benedetto, Anna Di, additional, Ercolani, Cristiana, additional, Pescarmona, Edoardo, additional, Pizzuti, Laura, additional, Sperati, Francesca, additional, Signore, Michele, additional, Vitale, Sara, additional, Schiavoni, Giovanna, additional, Mattei, Fabrizio, additional, De Ninno, Adele, additional, Businaro, Luca, additional, Lucarini, Valeria, additional, Bracci, Laura, additional, Aricò, Eleonora, additional, Ziccheddu, Giovanna, additional, Facchiano, Francesco, additional, Rossi, Stefania, additional, Sanchez, Massimo, additional, Boe, Alessandra, additional, Biffoni, Mauro, additional, De Maria, Ruggero, additional, and Vitale, Ilio, additional

Published
2021
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31. Anticancer Effects of Sublingual Type I IFN in Combination with Chemotherapy in Implantable and Spontaneous Tumor Models

Author

Ciccolella, Maria, primary, Andreone, Sara, additional, Mancini, Jacopo, additional, Sestili, Paola, additional, Negri, Donatella, additional, Pacca, Anna Maria, additional, D’Urso, Maria Teresa, additional, Macchia, Daniele, additional, Canese, Rossella, additional, Pang, Ken, additional, SaiYing Ko, Thomas, additional, Decadt, Yves, additional, Schiavoni, Giovanna, additional, Mattei, Fabrizio, additional, Belardelli, Filippo, additional, Aricò, Eleonora, additional, and Bracci, Laura, additional

Published
2021
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34. Clinical and antitumor immune responses In Relapsed/Refractory Follicular Lymphoma patients after intranodal injections of IFNα-Dendritic Cells and Rituximab

Author

Cox, Maria Christina, Castiello, Luciano, Mattei, Mauro, Santodonato, Laura, D'Agostino, Giuseppina, Muraro, Elena, Martorelli, Debora, Lapenta, Caterina, Di Napoli, Arianna, Di Landro, Francesca, Cangemi, Michela, Pavan, Antonio, Castaldo, Paolo, Hohaus, Stefan, Donati, Simona, Montefiore, Enrica, Berdini, Cinzia, Carlei, Davide, Monque, Domenica M, Ruco, Luigi, Prosperi, Daniela, Tafuri, Agostino, Spadaro, Francesca, Sestili, Paola, Spada, Massimo, Dolcetti, Riccardo, Santini, Stefano Maria, Rozera, Carmela, Aricò, Eleonora, Capone, Imerio, and Belardelli, Filippo

Subjects
follicular lymphoma, immunotherapy, dendritic cells
Published
2019

37. Clinical and Antitumor Immune Responses in Relapsed/Refractory Follicular Lymphoma Patients after Intranodal Injections of IFNα-Dendritic Cells and Rituximab: a Phase I Clinical Trial

Author

Cox, M. Christina, primary, Castiello, Luciano, additional, Mattei, Mauro, additional, Santodonato, Laura, additional, D'Agostino, Giuseppina, additional, Muraro, Elena, additional, Martorelli, Debora, additional, Lapenta, Caterina, additional, Di Napoli, Arianna, additional, Di Landro, Francesca, additional, Cangemi, Michela, additional, Pavan, Antonio, additional, Castaldo, Paolo, additional, Hohaus, Stefan, additional, Donati, Simona, additional, Montefiore, Enrica, additional, Berdini, Cinzia, additional, Carlei, Davide, additional, Monque, Domenica M., additional, Ruco, Luigi, additional, Prosperi, Daniela, additional, Tafuri, Agostino, additional, Spadaro, Francesca, additional, Sestili, Paola, additional, Spada, Massimo, additional, Dolcetti, Riccardo, additional, Santini, Stefano M., additional, Rozera, Carmela, additional, Aricò, Eleonora, additional, Capone, Imerio, additional, and Belardelli, Filippo, additional

Published
2019
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39. Concomitant detection of IFNα signature and activated monocyte/dendritic cell precursors in the peripheral blood of IFNα-treated subjects at early times after repeated local cytokine treatments

Author

Rizza Paola, Panelli Monica C, Urbani Francesca, Castiello Luciano, Aricò Eleonora, Wang Ena, Marincola Francesco M, and Belardelli Filippo

Subjects
Medicine
Abstract

Abstract Background Interferons alpha (IFNα) are the cytokines most widely used in clinical medicine for the treatment of cancer and viral infections. Among the immunomodulatory activities possibly involved in their therapeutic efficacy, the importance of IFNα effects on dendritic cells (DC) differentiation and activation has been considered. Despite several studies exploiting microarray technology to characterize IFNα mechanisms of action, there is currently no consensus on the core signature of these cytokines in the peripheral blood of IFNα-treated individuals, as well as on the existence of blood genomic and proteomic markers of low-dose IFNα administered as a vaccine adjuvant. Methods Gene profiling analysis with microarray was performed on PBMC isolated from melanoma patients and healthy individuals 24 hours after each repeated injection of low-dose IFNα, administered as vaccine adjuvant in two separate clinical trials. At the same time points, cytofluorimetric analysis was performed on CD14+ monocytes, to detect the phenotypic modifications exerted by IFNα on antigen presenting cells precursors. Results An IFNα signature was consistently observed in both clinical settings 24 hours after each repeated administration of the cytokine. The observed modulation was transient, and did not reach a steady state level refractory to further stimulations. The molecular signature observed ex vivo largely matched the one detected in CD14+ monocytes exposed in vitro to IFNα, including the induction of CXCL10 at the transcriptional and protein level. Interestingly, IFNα ex vivo signature was paralleled by an increase in the percentage and expression of costimulatory molecules by circulating CD14+/CD16+ monocytes, indicated as natural precursors of DC in response to danger signals. Conclusions Our results provide new insights into the identification of a well defined molecular signature as biomarker of IFNα administered as immune adjuvants, and for the characterization of new molecular and cellular players, such as CXCL10 and CD14+/CD16+ cells, mediating and possibly predicting patient response to these cytokines.

Published
2011
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40. Immature monocyte derived dendritic cells gene expression profile in response to Virus-Like Particles stimulation

Author

Marincola Francesco M, Lewis George K, Tagliamonte Maria, Tornesello Maria, Wang Ena, Aricò Eleonora, Buonaguro Franco M, and Buonaguro Luigi

Subjects
Medicine
Abstract

Abstract We have recently developed a candidate HIV-1 vaccine model based on HIV-1 Pr55gag Virus-Like Particles (HIV-VLPs), produced in a baculovirus expression system and presenting a gp120 molecule from an Ugandan HIV-1 isolate of the clade A (HIV-VLPAs). The HIV-VLPAs induce in Balb/c mice systemic and mucosal neutralizing Antibodies as well as cytotoxic T lymphocytes, by intra-peritoneal as well as intra-nasal administration. Moreover, we have recently shown that the baculovirus-expressed HIV-VLPs induce maturation and activation of monocyte-derived dendritic cells (MDDCs) which, in turn, produce Th1- and Th2-specific cytokines and stimulate in vitro a primary and secondary response in autologous CD4+ T cells. In the present manuscript, the effects of the baculovirus-expressed HIV-VLPAs on the genomic transcriptional profile of MDDCs obtained from normal healthy donors have been evaluated. The HIV-VLPA stimulation, compared to both PBS and LPS treatment, modulate the expression of genes involved in the morphological and functional changes characterizing the MDDCs activation and maturation. The results of gene profiling analysis here presented are highly informative on the global pattern of gene expression alteration underlying the activation of MDDCs by HIV-VLPAs at the early stages of the immune response and may be extremely helpful for the identification of exclusive activation markers.

Published
2005
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41. High Response Rate in Relapsed/Refractory Follicular Lymphoma Following Personalised Immunotherapy with Intranodal IFN-Alfa-Dendritic-Cell and Rituximab

Author

Cox, M. Christina Christina, primary, Rozera, Carmela, additional, Mattei, Mauro, additional, Muraro, Elena, additional, Aricò, Eleonora, additional, Di Napoli, Arianna, additional, Pavan, Antonio, additional, Di Landro, Francesca, additional, Santodonato, Laura, additional, Martorelli, Debora, additional, D'Agostino, Giuseppina, additional, Lapenta, Caterina, additional, Hohaus, Stefan, additional, Cuccaro, Annarosa, additional, Cantonetti, Maria, additional, Zoli, Valerio, additional, Berdini, Cinzia, additional, Sonia, Borgioni, additional, Pupo, Livio, additional, Prosperi, Daniela, additional, Donati, Simona, additional, Napolitano, Mariarosaria, additional, Michela, Cangemi, additional, Montefiore, Enrica, additional, Carlei, Davide, additional, Monque, Domenica, additional, Ruco, Luigi, additional, Tafuri, Agostino, additional, Dolcetti, Riccardo, additional, Santini, Stefano Maria, additional, Capone, Imerio, additional, and Belardelli, Filippo, additional

Published
2018
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42. Disruption of IFN-I Signaling Promotes HER2/Neu Tumor Progression and Breast Cancer Stem Cells

Author

Castiello, Luciano, primary, Sestili, Paola, additional, Schiavoni, Giovanna, additional, Dattilo, Rosanna, additional, Monque, Domenica M., additional, Ciaffoni, Fiorella, additional, Iezzi, Manuela, additional, Lamolinara, Alessia, additional, Sistigu, Antonella, additional, Moschella, Federica, additional, Pacca, Anna Maria, additional, Macchia, Daniele, additional, Ferrantini, Maria, additional, Zeuner, Ann, additional, Biffoni, Mauro, additional, Proietti, Enrico, additional, Belardelli, Filippo, additional, and Aricò, Eleonora, additional

Published
2018
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43. Social threat exposure in juvenile mice promotes cocaine-seeking by altering blood clotting and brain vasculature.

Author

Lo Iacono, Luisa, Valzania, Alessandro, Visco‐Comandini, Federica, Aricò, Eleonora, Viscomi, Maria Teresa, Castiello, Luciano, Oddi, Diego, D'Amato, Francesca R., Bisicchia, Elisa, Ermakova, Olga, Puglisi‐Allegra, Stefano, Carola, Valeria, Visco-Comandini, Federica, Aricò, Eleonora, and Puglisi-Allegra, Stefano

Subjects
BLOOD coagulation disorders, SUBSTANCE-induced disorders, DRUG abuse, DRUG abstinence, CHILD abuse, ASPIRIN, LABORATORY mice, ANIMAL behavior, ANIMAL experimentation, ANIMALS, BIOLOGICAL models, BLOOD coagulation, BRAIN, COCAINE, MICE, SOCIAL skills, PSYCHOLOGICAL stress, SUBSTANCE abuse
Abstract

Childhood maltreatment is associated with increased severity of substance use disorder and frequent relapse to drug use following abstinence. However, the molecular and neurobiological substrates that are engaged during early traumatic events and mediate the greater risk of relapse are poorly understood and knowledge of risk factors is to date extremely limited. In this study, we modeled childhood maltreatment by exposing juvenile mice to a threatening social experience (social stressed, S-S). We showed that S-S experience influenced the propensity to reinstate cocaine-seeking after periods of withdrawal in adulthood. By exploring global gene expression in blood leukocytes we found that this behavioral phenotype was associated with greater blood coagulation. In parallel, impairments in brain microvasculature were observed in S-S mice. Furthermore, treatment with an anticoagulant agent during withdrawal abolished the susceptibility to reinstate cocaine-seeking in S-S mice. These findings provide novel insights into a possible molecular mechanism by which childhood maltreatment heightens the risk for relapse in cocaine-dependent individuals. [ABSTRACT FROM AUTHOR]

Published
2017
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46. Social threat exposure in juvenile mice promotes cocaine-seeking by altering blood clotting and brain vasculature

Author

Lo Iacono, Luisa, primary, Valzania, Alessandro, additional, Visco-Comandini, Federica, additional, Aricò, Eleonora, additional, Viscomi, Maria Teresa, additional, Castiello, Luciano, additional, Oddi, Diego, additional, D'Amato, Francesca R., additional, Bisicchia, Elisa, additional, Ermakova, Olga, additional, Puglisi-Allegra, Stefano, additional, and Carola, Valeria, additional

Published
2016
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47. Engineered exosomes emerging from muscle cells break immune tolerance to HER2 in transgenic mice and induce antigen-specific CTLs upon challenge by human dendritic cells.

Author

Anticoli, Simona, Aricò, Eleonora, Arenaccio, Claudia, Manfredi, Francesco, Chiozzini, Chiara, Olivetta, Eleonora, Ferrantelli, Flavia, Lattanzi, Laura, D’Urso, Maria Teresa, Proietti, Enrico, and Federico, Maurizio

Subjects
*EXOSOMES, *MUSCLE cells, *IMMUNOLOGICAL tolerance, *CYTOTOXIC T cells, *DENDRITIC cells, *LABORATORY mice
Abstract

We recently described a novel biotechnological platform for the production of unrestricted cytotoxic T lymphocyte (CTL) vaccines. It relies on in vivo engineering of exosomes, i.e., nanovesicles constitutively released by all cells, with full-length antigens of choice upon fusion with an exosome-anchoring protein referred to as Nef. They are produced upon intramuscular injection of a DNA vector and, when uploaded with a viral tumor antigen, were found to elicit an immune response inhibiting the tumor growth in a model of transplantable tumors. However, for a possible application in cancer immunotherapy, a number of key issues remained unmet. Among these, we investigated: (i) whether the immunogenic stimulus induced by the engineered exosomes can break immune tolerance, and (ii) their effectiveness when applied in human system. As a model of immune tolerance, we considered mice transgenic for the expression of activated rat HER2/neu which spontaneously develop adenocarcinomas in all mammary glands. When these mice were injected with a DNA vector expressing the product of fusion between Nef and the extracellular domain of HER2/neu, antigen-specific CD8 T lymphocytes became readily detectable. This immune response associated with a HER2-directed CTL activity and a significant delay in tumor development. On the other hand, through cross-priming experiments, we demonstrated the effectiveness of the engineered exosomes emerging from transfected human primary muscle cells in inducing antigen-specific CTLs. We propose our CTL vaccine platform as part of new immunotherapy strategies against tumors expressing self-antigens, i.e., products highly expressed in oncologic lesions but tolerated by the immune system. Key messages: [ABSTRACT FROM AUTHOR]

Published
2018
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49. Intratumoral injection of IFN-alpha dendritic cells after dacarbazine activates anti-tumor immunity: results from a phase I trial in advanced melanoma

Author

Rozera, Carmela, primary, Cappellini, Giancarlo Antonini, additional, D’Agostino, Giuseppina, additional, Santodonato, Laura, additional, Castiello, Luciano, additional, Urbani, Francesca, additional, Macchia, Iole, additional, Aricò, Eleonora, additional, Casorelli, Ida, additional, Sestili, Paola, additional, Montefiore, Enrica, additional, Monque, Domenica, additional, Carlei, Davide, additional, Napolitano, Mariarosaria, additional, Rizza, Paola, additional, Moschella, Federica, additional, Buccione, Carla, additional, Belli, Roberto, additional, Proietti, Enrico, additional, Pavan, Antonio, additional, Marchetti, Paolo, additional, Belardelli, Filippo, additional, and Capone, Imerio, additional

Published
2015
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50. Concomitant detection of IFNα signature and activated monocyte/dendritic cell precursors in the peripheral blood of IFNα-treated subjects at early times after repeated local cytokine treatments.

Author

Aricò, Eleonora, Castiello, Luciano, Urbani, Francesca, Rizza, Paola, Panelli, Monica C., Wang, Ena, Marincola, Francesco M., Belardelli, Filippo, and Aricò, Eleonora

Subjects
*INTERFERONS, *CYTOKINES, *LEUCOCYTES, *DENDRITIC cells, *MONOCYTES
Abstract

Background: Interferons alpha (IFNα) are the cytokines most widely used in clinical medicine for the treatment of cancer and viral infections. Among the immunomodulatory activities possibly involved in their therapeutic efficacy, the importance of IFNα effects on dendritic cells (DC) differentiation and activation has been considered. Despite several studies exploiting microarray technology to characterize IFNα mechanisms of action, there is currently no consensus on the core signature of these cytokines in the peripheral blood of IFNα-treated individuals, as well as on the existence of blood genomic and proteomic markers of low-dose IFNα administered as a vaccine adjuvant.Methods: Gene profiling analysis with microarray was performed on PBMC isolated from melanoma patients and healthy individuals 24 hours after each repeated injection of low-dose IFNα, administered as vaccine adjuvant in two separate clinical trials. At the same time points, cytofluorimetric analysis was performed on CD14+ monocytes, to detect the phenotypic modifications exerted by IFNα on antigen presenting cells precursors.Results: An IFNα signature was consistently observed in both clinical settings 24 hours after each repeated administration of the cytokine. The observed modulation was transient, and did not reach a steady state level refractory to further stimulations. The molecular signature observed ex vivo largely matched the one detected in CD14+ monocytes exposed in vitro to IFNα, including the induction of CXCL10 at the transcriptional and protein level. Interestingly, IFNα ex vivo signature was paralleled by an increase in the percentage and expression of costimulatory molecules by circulating CD14+/CD16+ monocytes, indicated as natural precursors of DC in response to danger signals.Conclusions: Our results provide new insights into the identification of a well defined molecular signature as biomarker of IFNα administered as immune adjuvants, and for the characterization of new molecular and cellular players, such as CXCL10 and CD14+/CD16+ cells, mediating and possibly predicting patient response to these cytokines. [ABSTRACT FROM AUTHOR]

Published
2011
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