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101. Concurrent and orthogonal gold(I) and ruthenium(II) catalysis inside living cells

Author

Universidade de Santiago de Compostela. Centro de Investigación en Química Biolóxica e Materiais Moleculares, Universidade de Santiago de Compostela. Departamento de Química Orgánica, Vidal Vides, Cristian, Tomás Gamasa, María, Destito, Paolo, López García, Fernando, Mascareñas Cid, José Luis, Universidade de Santiago de Compostela. Centro de Investigación en Química Biolóxica e Materiais Moleculares, Universidade de Santiago de Compostela. Departamento de Química Orgánica, Vidal Vides, Cristian, Tomás Gamasa, María, Destito, Paolo, López García, Fernando, and Mascareñas Cid, José Luis

Abstract

The viability of building artificial metabolic pathways within a cell will depend on our ability to design biocompatible and orthogonal catalysts capable of achieving non-natural transformations. In this context, transition metal complexes offer unique possibilities to develop catalytic reactions that do not occur in nature. However, translating the potential of metal catalysts to living cells poses numerous challenges associated to their biocompatibility, and their stability and reactivity in crowded aqueous environments. Here we report a goldmediated C–C bond formation that occurs in complex aqueous habitats, and demonstrate that the reaction can be translated to living mammalian cells. Key to the success of the process is the use of designed, water-activatable gold chloride complexes. Moreover, we demonstrate the viability of achieving the gold-promoted process in parallel with a ruthenium-mediated reaction, inside living cells, and in a bioorthogonal and mutually orthogonal manner

Published
2018

102. Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study

Author

Porreca, A., Noale, M., Artibani, W., Bassi, P. F., Bertoni, F., Bracarda, S., Conti, G. N., Corvo, R., Gacci, M., Graziotti, P., Magrini, S. M., Mirone, V., Montironi, R., Muto, G., Pecoraro, S., Ricardi, U., Russi, E., Tubaro, A., Zagonel, V., Crepaldi, G., Maggi, S., Alitto, A. R., Ambrosi, E., Antonelli, A., Aristei, C., Barbieri, M., Bardari, F., Bardoscia, L., Barra, S., Bartoncini, S., Basso, U., Becherini, C., Bellavita, R., Bergamaschi, F., Berlingheri, S., Berruti, A., Borghesi, M., Bortolus, R., Borzillo, V., Bosetti, D., Bove, G., Bove, P., Maurizio, B., Alessio, B., Giorgio, B., Eugenio, B., Alberto, B., Michela, B., Consuelo, B., Giovanni, C., Michela, C., Giuseppe, C., Giorgio, C., Emanuele, C., Elisabetta, C., Gianpiero, C., Susanna, C., Catucci, F., Dario, C. F., Ofelia, C., Antonio, C., Francesco, C., Tommaso, C., Claudia, C., Devis, C., Franco, C., Matteo, C., Paolo, C., Fiorenza, C., Luigi, C., Cosimo, N., Cristiano, O., D'angelillo, R. M., Da Pozzo, L., D'agostino, D., D'elia, C., Dandrea, M., De Angelis, M., De Angelis, P., De Cobelli, O., De Concilio, B., De Lisa, A., De Luca, S., De Stefani, A., Deantoni, C. L., Degli, E. C., Destito, A., Detti, B., Di Muzio, N., Di Stasio, A., Di Stefano, C., Di Trapani, D., Difino, G., Falivene, S., Farullo, G., Fedelini, P., Ferrari, I., Ferrau, F., Ferro, M., Fodor, A., Fontanta, F., Francesca, F., Francolini, G., Frata, P., Frezza, G., Gabriele, P., Galeandro, M., Garibaldi, E., Gennari, P. G., Gentilucci, A., Giacobbe, A., Giussani, L., Giusti, G., Gontero, P., Guarneri, A., Guida, C., Gurioli, A., Huqi, D., Imbimbo, C., Ingrosso, G., Iotti, C., Italia, C., La Mattina, P., Lamanna, E., Lastrucci, L., Lazzari, G., Liberale, F., Liguori, G., Lisi, R., Lohr, F., Lombardo, R., Lovisolo, J. A. J., Ludovico, G. M., Macchione, N., Maggio, F., Malizia, M., Manasse, G., Mandoliti, G., Mantini, G., Marafioti, L., Marciello, L., Marconi, A. M., Martilotta, A., Marzano, S., Masciullo, S., Maso, G., Massenzo, A., Mazzeo, E., Mearini, L., Medoro, S., Mole, R., Monesi, G., Montanari, E., Montefiore, F., Montesi, G., Morgia, G., Moro, G., Muscas, G., Musio, D., Muto, P., Muzzonigro, G., Napodano, G., Negro, C. L. A., Nidini, M., Ntreta, M., Orsatti, M., Palazzolo, C., Palumbo, I., Parisi, A., Parma, P., Pavan, N., Pericolini, M., Pinto, F., Pistone, A., Pizzuti, V., Platania, A., Polli, C., Pomara, G., Ponti, E., Porcaro, A. B., Porpiglia, F., Pugliese, D., Pycha, A., Raguso, G., Rampini, A., Randone, D. F., Roboldi, V., Roscigno, M., Ruggieri, M. P., Ruoppo, G., Sanseverino, R., Santacaterina, A., Santarsieri, M., Santoni, R., Scagliarini, S., Scagliotti, G. V., Scanzi, M., Scarcia, M., Schiavina, R., Sciarra, A., Sciorio, C., Scolaro, T., Scuzzarella, S., Selvaggio, O., Serao, A., Serni, S., Signor, M. A., Silvani, M., Silvano, G., Silvestris, F., Simeone, C., Simone, V., Spagnoletti, G., Spinelli, M. G., Squillace, L., Tombolini, V., Toninelli, M., Triggiani, L., Trinchieri, A., Trodella, L. E., Trodella, L., Trombetta, C., Tronnolone, L., Tucci, M., Urzi, D., Valdagni, R., Valeriani, M., Vanoli, M., Vitali, E., Volpe, A., Zaramella, S., Zeccolini, G., Zini, G., Porreca A., Bassi P. F. (ORCID:0000-0002-4313-8427), Alitto A. R., Bove P., D'angelillo R. M., Guarneri A., Mantini G. (ORCID:0000-0001-5303-4499), Porreca, A., Noale, M., Artibani, W., Bassi, P. F., Bertoni, F., Bracarda, S., Conti, G. N., Corvo, R., Gacci, M., Graziotti, P., Magrini, S. M., Mirone, V., Montironi, R., Muto, G., Pecoraro, S., Ricardi, U., Russi, E., Tubaro, A., Zagonel, V., Crepaldi, G., Maggi, S., Alitto, A. R., Ambrosi, E., Antonelli, A., Aristei, C., Barbieri, M., Bardari, F., Bardoscia, L., Barra, S., Bartoncini, S., Basso, U., Becherini, C., Bellavita, R., Bergamaschi, F., Berlingheri, S., Berruti, A., Borghesi, M., Bortolus, R., Borzillo, V., Bosetti, D., Bove, G., Bove, P., Maurizio, B., Alessio, B., Giorgio, B., Eugenio, B., Alberto, B., Michela, B., Consuelo, B., Giovanni, C., Michela, C., Giuseppe, C., Giorgio, C., Emanuele, C., Elisabetta, C., Gianpiero, C., Susanna, C., Catucci, F., Dario, C. F., Ofelia, C., Antonio, C., Francesco, C., Tommaso, C., Claudia, C., Devis, C., Franco, C., Matteo, C., Paolo, C., Fiorenza, C., Luigi, C., Cosimo, N., Cristiano, O., D'angelillo, R. M., Da Pozzo, L., D'agostino, D., D'elia, C., Dandrea, M., De Angelis, M., De Angelis, P., De Cobelli, O., De Concilio, B., De Lisa, A., De Luca, S., De Stefani, A., Deantoni, C. L., Degli, E. C., Destito, A., Detti, B., Di Muzio, N., Di Stasio, A., Di Stefano, C., Di Trapani, D., Difino, G., Falivene, S., Farullo, G., Fedelini, P., Ferrari, I., Ferrau, F., Ferro, M., Fodor, A., Fontanta, F., Francesca, F., Francolini, G., Frata, P., Frezza, G., Gabriele, P., Galeandro, M., Garibaldi, E., Gennari, P. G., Gentilucci, A., Giacobbe, A., Giussani, L., Giusti, G., Gontero, P., Guarneri, A., Guida, C., Gurioli, A., Huqi, D., Imbimbo, C., Ingrosso, G., Iotti, C., Italia, C., La Mattina, P., Lamanna, E., Lastrucci, L., Lazzari, G., Liberale, F., Liguori, G., Lisi, R., Lohr, F., Lombardo, R., Lovisolo, J. A. J., Ludovico, G. M., Macchione, N., Maggio, F., Malizia, M., Manasse, G., Mandoliti, G., Mantini, G., Marafioti, L., Marciello, L., Marconi, A. M., Martilotta, A., Marzano, S., Masciullo, S., Maso, G., Massenzo, A., Mazzeo, E., Mearini, L., Medoro, S., Mole, R., Monesi, G., Montanari, E., Montefiore, F., Montesi, G., Morgia, G., Moro, G., Muscas, G., Musio, D., Muto, P., Muzzonigro, G., Napodano, G., Negro, C. L. A., Nidini, M., Ntreta, M., Orsatti, M., Palazzolo, C., Palumbo, I., Parisi, A., Parma, P., Pavan, N., Pericolini, M., Pinto, F., Pistone, A., Pizzuti, V., Platania, A., Polli, C., Pomara, G., Ponti, E., Porcaro, A. B., Porpiglia, F., Pugliese, D., Pycha, A., Raguso, G., Rampini, A., Randone, D. F., Roboldi, V., Roscigno, M., Ruggieri, M. P., Ruoppo, G., Sanseverino, R., Santacaterina, A., Santarsieri, M., Santoni, R., Scagliarini, S., Scagliotti, G. V., Scanzi, M., Scarcia, M., Schiavina, R., Sciarra, A., Sciorio, C., Scolaro, T., Scuzzarella, S., Selvaggio, O., Serao, A., Serni, S., Signor, M. A., Silvani, M., Silvano, G., Silvestris, F., Simeone, C., Simone, V., Spagnoletti, G., Spinelli, M. G., Squillace, L., Tombolini, V., Toninelli, M., Triggiani, L., Trinchieri, A., Trodella, L. E., Trodella, L., Trombetta, C., Tronnolone, L., Tucci, M., Urzi, D., Valdagni, R., Valeriani, M., Vanoli, M., Vitali, E., Volpe, A., Zaramella, S., Zeccolini, G., Zini, G., Porreca A., Bassi P. F. (ORCID:0000-0002-4313-8427), Alitto A. R., Bove P., D'angelillo R. M., Guarneri A., and Mantini G. (ORCID:0000-0001-5303-4499)

Abstract

Background: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care.

Published
2018

103. Concurrent and orthogonal gold(I) and ruthenium(II) catalysis inside living cells

Author

European Commission, Xunta de Galicia, Ministerio de Economía, Industria y Competitividad (España), Vidal, Cristina, Tomás-Gamasa, María, Destito, Paolo, López, Fernando, Mascareñas, José L., European Commission, Xunta de Galicia, Ministerio de Economía, Industria y Competitividad (España), Vidal, Cristina, Tomás-Gamasa, María, Destito, Paolo, López, Fernando, and Mascareñas, José L.

Abstract

The viability of building artificial metabolic pathways within a cell will depend on our ability to design biocompatible and orthogonal catalysts capable of achieving non-natural transformations. In this context, transition metal complexes offer unique possibilities to develop catalytic reactions that do not occur in nature. However, translating the potential of metal catalysts to living cells poses numerous challenges associated to their biocompatibility, and their stability and reactivity in crowded aqueous environments. Here we report a gold-mediated C-C bond formation that occurs in complex aqueous habitats, and demonstrate that the reaction can be translated to living mammalian cells. Key to the success of the process is the use of designed, water-activatable gold chloride complexes. Moreover, we demonstrate the viability of achieving the gold-promoted process in parallel with a ruthenium-mediated reaction, inside living cells, and in a bioorthogonal and mutually orthogonal manner.

Published
2018

104. Canine parvovirus-like particles, a novel nanomaterial for tumor targeting

Author

Destito Giuseppe, Singh Pratik, Schneemann Anette, and Manchester Marianne

Subjects
Biotechnology, TP248.13-248.65, Medical technology, R855-855.5
Abstract

Abstract Specific targeting of tumor cells is an important goal for the design of nanotherapeutics for the treatment of cancer. Recently, viruses have been explored as nano-containers for specific targeting applications, however these systems typically require modification of the virus surface using chemical or genetic means to achieve tumor-specific delivery. Interestingly, there exists a subset of viruses with natural affinity for receptors on tumor cells that could be exploited for nanotechnology applications. For example, the canine parvovirus (CPV) utilizes transferrin receptors (TfRs) for binding and cell entry into canine as well as human cells. TfRs are over-expressed by a variety of tumor cells and are widely being investigated for tumor-targeted drug delivery. We explored whether the natural tropism of CPV to TfRs could be harnessed for targeting tumor cells. Towards this goal, CPV virus-like particles (VLPs) produced by expression of the CPV-VP2 capsid protein in a baculovirus expression system were examined for attachment of small molecules and delivery to tumor cells. Structural modeling suggested that six lysines per VP2 subunit are presumably addressable for bioconjugation on the CPV capsid exterior. Between 45 and 100 of the possible 360 lysines/particle could be routinely derivatized with dye molecules depending on the conjugation conditions. Dye conjugation also demonstrated that the CPV-VLPs could withstand conditions for chemical modification on lysines. Attachment of fluorescent dyes neither impaired binding to the TfRs nor affected internalization of the 26 nm-sized VLPs into several human tumor cell lines. CPV-VLPs therefore exhibit highly favorable characteristics for development as a novel nanomaterial for tumor targeting.

Published
2006
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105. Ruthenium-Catalyzed Azide–Thioalkyne Cycloadditions in Aqueous Media: A Mild, Orthogonal, and Biocompatible Chemical Ligation

Author

José L. Mascareñas, Hélio Faustino, Fernando López, José R. Couceiro, Paolo Destito, Universidade de Santiago de Compostela. Centro de Investigación en Química Biolóxica e Materiais Moleculares, Universidade de Santiago de Compostela. Departamento de Química Orgánica, European Commission, Xunta de Galicia, and Ministerio de Economía, Industria y Competitividad (España)

Subjects
Azides, chemistry.chemical_element, 010402 general chemistry, 01 natural sciences, Catalysis, Ruthenium, chemistry.chemical_compound, Organic chemistry, Cycloaddition, Aqueous solution, Chemistry, 010405 organic chemistry, Click chemistry, Communication, Regioselectivity, General Chemistry, General Medicine, Communications, 0104 chemical sciences, Alkynes, Chemical ligations, Chemical ligation, Azide, Bioorthogonal chemistry
Abstract

The development of efficient metal-promoted bioorthogonal ligations remains as a major scientific challenge. Demonstrated herein is that azides undergo efficient and regioselective room-temperature annulations with thioalkynes in aqueous milieu when treated with catalytic amounts of a suitable ruthenium complex. The reaction is compatible with different biomolecules, and can be carried out in complex aqueous mixtures such as phosphate buffered saline, cell lysates, fetal bovine serum, and even living bacteria (E. coli). Importantly, the reaction is mutually compatible with the classical CuAAC., This work has received financial support from Spanish grants (SAF2016-76689-R and SAF2013-41943-R), the Xunta de Galicia (2015-CP082 and Centro Singular de Investigaciln de Galicia accreditation 2016-2019 ED431G/09), the European Union (European Regional Development Fund - ERDF), and the ERC (Adv. Grant 340055). We also thank the Orfeo- Cinqa network CTQ2016-81797-REDC, and T. Seedat and V. Fraga for preliminary experiments

Published
2017

106. Correction: Generation and Improvement of Effector Function of a Novel Broadly Reactive and Protective Monoclonal Antibody against Pneumococcal Surface Protein A of Streptococcus pneumoniae

Author

Lilia Koriazova, Cécile Martin, Tsuguo Kubota, Takayuki Ota, Yutaka Kanda, Sarah Sunrise Bubeck, Tomoyuki Tahara, Sascha A. Kristian, Brian C. Groff, Rebecca Cho, Giuseppe Destito, and John Laudenslager

Subjects
0301 basic medicine, Multidisciplinary, biology, medicine.drug_class, Effector, lcsh:R, lcsh:Medicine, medicine.disease, Monoclonal antibody, medicine.disease_cause, Immunoglobulin G, Microbiology, Complement system, 03 medical and health sciences, Pneumococcal infections, 030104 developmental biology, Epitope mapping, Streptococcus pneumoniae, Immunology, medicine, biology.protein, lcsh:Q, Antibody, lcsh:Science
Abstract

A proof-of-concept study evaluating the potential of Streptococcus pneumoniae Pneumococcal Surface Protein A (PspA) as a passive immunization target was conducted. We describe the generation and isolation of several broadly reactive mouse anti-PspA monoclonal antibodies (mAbs). MAb 140H1 displayed (i) 98% strain coverage, (ii) activity in complement deposition and opsonophagocytic killing (OPK) assays, which are thought to predict the in vivo efficacy of anti-pneumococcal mAbs, (iii) efficacy in mouse sepsis models both alone and in combination with standard-of-care antibiotics, and (iv) therapeutic activity in a mouse pneumonia model. Moreover, we demonstrate that antibody engineering can significantly enhance anti-PspA mAb effector function. We believe that PspA has promising potential as a target for the therapy of invasive pneumococcal disease by mAbs, which could be used alone or in conjunction with standard-of-care antibiotics.

Published
2017

110. Correction to Discovery of the Hemifumarate and (α-l-Alanyloxy)methyl Ether as Prodrugs of an Antirheumatic Oxindole: Prodrugs for the Enolic OH Group

Author

Robinson, Ralph P., primary, Reiter, Lawrence A., additional, Barth, Wayne E., additional, Campeta, Anthony M., additional, Cooper, Kelvin, additional, Cronin, Brian J., additional, Destito, Rosalina, additional, Donahue, Kathleen M., additional, Falkner, Fred C., additional, Fiese, Eugene F., additional, Johnson, Diane L., additional, Kuperman, Alexander V., additional, Liston, Theodore E., additional, Malloy, Deborah, additional, Martin, John J., additional, Mitchell, David Y., additional, Rusek, Frank W., additional, Shamblin, Sheri L., additional, and Wright, Charles F., additional

Published
2018
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112. Ruthenium-Catalyzed Azide–Thioalkyne Cycloadditions in Aqueous Media: A Mild, Orthogonal, and Biocompatible Chemical Ligation

Author

Universidade de Santiago de Compostela. Centro de Investigación en Química Biolóxica e Materiais Moleculares, Universidade de Santiago de Compostela. Departamento de Química Orgánica, Destito, Paolo, Rodríguez Couceiro, José, Faustino, Hélio, López García, Fernando, Mascareñas Cid, José Luis, Universidade de Santiago de Compostela. Centro de Investigación en Química Biolóxica e Materiais Moleculares, Universidade de Santiago de Compostela. Departamento de Química Orgánica, Destito, Paolo, Rodríguez Couceiro, José, Faustino, Hélio, López García, Fernando, and Mascareñas Cid, José Luis

Abstract

The development of efficient metal-promoted bioorthogonal ligations remains as a major scientific challenge. Demonstrated herein is that azides undergo efficient and regioselective room-temperature annulations with thioalkynes in aqueous milieu when treated with catalytic amounts of a suitable ruthenium complex. The reaction is compatible with different biomolecules, and can be carried out in complex aqueous mixtures such as phosphate buffered saline, cell lysates, fetal bovine serum, and even living bacteria (E. coli). Importantly, the reaction is mutually compatible with the classical CuAAC

Published
2017

113. Ruthenium-Catalyzed Azide–Thioalkyne Cycloadditions in Aqueous Media: A Mild, Orthogonal, and Biocompatible Chemical Ligation

Author

European Commission, Xunta de Galicia, Ministerio de Economía, Industria y Competitividad (España), Destito, Paolo, Couceiro, José R., Faustino, Helio, López, Fernando, Mascareñas, José L., European Commission, Xunta de Galicia, Ministerio de Economía, Industria y Competitividad (España), Destito, Paolo, Couceiro, José R., Faustino, Helio, López, Fernando, and Mascareñas, José L.

Abstract

The development of efficient metal-promoted bioorthogonal ligations remains as a major scientific challenge. Demonstrated herein is that azides undergo efficient and regioselective room-temperature annulations with thioalkynes in aqueous milieu when treated with catalytic amounts of a suitable ruthenium complex. The reaction is compatible with different biomolecules, and can be carried out in complex aqueous mixtures such as phosphate buffered saline, cell lysates, fetal bovine serum, and even living bacteria (E. coli). Importantly, the reaction is mutually compatible with the classical CuAAC.

Published
2017

114. Pros-IT CNR: an Italian prostate cancer monitoring project

Author

Bassi, Pierfrancesco, Maggi, Ilaria Stefania, Artibani, Walter, Bassi, Pier Francesco, Bertoni, Filippo, Bracarda, Sergio, Conti, Giario Natale, Corvò, Renzo, Gacci, Mauro, Graziotti, Pierpaolo, Magrini, Stefano Maria, Maurizi Enrici, Riccardo, Mirone, Vincenzo, Montironi, Rodolfo, Muto, Giovanni, Pecoraro, Stefano, Porreca, Angelo, Ricardi, Umberto, Tubaro, Andrea, Zagonel, Vittorina, Zattoni, Filiberto, Crepaldi, Gaetano, Noale, Marianna, Alitto, Anna Rita, Ambrosi, Enrica, Antonelli, Alessandro, Aristei, Cynthia, Barbieri, Michele, Bardari, Franco, Bardoscia, Lilia, Barra, Salvina, Bartoncini, Sara, Basso, Umberto, Becherini, Carlotta, Bellavita, Rita, Bergamaschi, Franco, Berlingheri, Stefania, Berruti, Alfredo, Borghesi, Marco, Bortolus, Roberto, Borzillo, Valentina, Bosetti, Davide, Bove, Giuseppe, Bove, Pierluigi, Brausi, Maurizio, Bruni, Alessio, Baldari, Giorgio Bruno Cristiano, Brunocilla, Eugenio, Buffoli, Alberto, Buglione, Michela, Buttigliero, Consuelo, Cacciamani, Giovanni, Caldiroli, Michela, Cardo, Giuseppe, Carmignani, Giorgio, Carrieri, Giuseppe, Castelli, Emanuele, Castrezzati, Elisabetta, Catalano, Gianpiero, Cattarino, Susanna, Catucci, Francesco, Cavallini Francolini, Dario, Ceccarini, Ofelia, Celia, Antonio, Chiancone, Francesco, Chini, Tommaso, Cianci, Claudia, Cisternino, Antonio, Collura, Devi, Corbella, Franco, Corinti, Matteo, Corsi, Paolo, Cortese, Fiorenza, Corti, Luigi, de Nunzio, Cosimo, Cristiano, Olga, D'Angelillo, Rolando Maria, Da Pozzo, Luigi, D'Agostino, Daniele, D’Andrea, David, Dandrea, Matteo, De Angelis, Michele, De Cobelli, Ottavio, De Concilio, Bernardino, De Lisa, Antonello, De Luca, Stefano, De Stefani, Agostina, Deantoni, Chiara Lucrezia, Degli Esposti, Claudio, Destito, Anna, Detti, Beatrice, Di Muzio, Nadia, Di Stasio, Andrea, Di Stefano, Calogero, Di Trapani, Danilo, Difino, Giuseppe, Falivene, Sara, Farullo, Giuseppe, Fedelini, Paolo, Ferrari, Ilaria, Ferrau, Francesco, Ferro, Matteo, Fodor, Andrei, Fontana, Francesco, Francesca, Francesco, Giulio, Francolini, Frata, Paolo, Frezza, Giovanni, Gabriele, Pietro, Galeandro, Maria, Garibaldi, Ida Marina Elisabetta, Gennari, Pietro, Gentilucci, Alessandro, Giacobbe, Alessandro, Giussani, Laura, Giusti, Giuseppe, Gontero, Paolo, Guarneri, Alessia, Guida, Cesare, Gurioli, Alberto, Huqi, Dorijan, Imbimbo, Ciro, Ingrosso, Gianluca, Iotti, Cinzia, Italia, Corrado, La Mattina, Pierdaniele, Lamanna, Enza, Lastrucci, Luciana, Lazzari, Grazia, Liberale, Fabiola, Liguori, Giovanni, Lisi, Roberto, Lohr, Frank, Lombardo, Riccardo, Lovisolo, Jon, Ludovico, Giuseppe Mario, Macchione, Nicola, Maggio, Francesca, Malizia, Michele, Manasse, Gianluca, Mandoliti, Giovanni, Mantini, Giovanna, Marafioti, Luigi, Marciello, Luisa, Marconi, Alberto Mario, Martillotta, Antonietta, Marzano, Salvino, Masciullo, Stefano, Maso, Gloria, Massenzo, Adele, Mazzeo, Ercole, Mearini, Luigi, Medoro, Serena, Molè, Rosa, Monesi, Giorgio, Montanari, Emanuele, Montefiore, Franco, Montesi, Giampaolo, Morgia, Giuseppe, Moro, Gregorio, Muscas, Giorgio, Musio, Daniela, Muto, Paolo, Muzzonigro, Giovanni, Napodano, Giorgio, Negro, Carlo Luigi Augusto, Nidini, Mattia, Ntreta, Maria, Orsatti, Marco, Palazzolo, Carmela, Palumbo, Isabella, Parisi, Alessandro, Parma, Paolo, Pavan, Nicola, Pericolini, Martina, Pinto, Francesco, Pistone, Antonio, Pizzuti, Valerio, Platania, Angelo, Polli, Caterina, Pomara, Giorgio, Ponti, Elisabetta, Porcaro, Antonio Benito, Porpiglia, Francesco, Pugliese, Dario, Pycha, Armin, Raguso, Giuseppe, Rampini, Andrea, Randone, Donato Franco, Roscigno, Marco, Ruggieri, Maria Paola, Ruoppo, Giuseppe, Sanseverino, Roberto, Santacaterina, Anna, Santarsieri, Michele, Santoni, Riccardo, Scagliarini, Sarah, Scagliotti, Giorgio Vittorio, Scanzi, Mauro, Scarcia, Marcello, Schiavina, Riccardo, Sciarra, Alessandro, Sciorio, Carmine, Scolaro, Tindaro, Scuzzarella, Salvatore, Selvaggio, Oscar, Serao, Armando, Serni, Sergio, Signor, Marco Andrea, Silvani, Mauro, Silvano, Giovanni, Silvestris, Franco, Simeone, Claudio, Simone, Valeria, Spagnoletti, Girolamo, Spinelli, Matteo Giulio, Squillace, Luigi, Tombolini, Vincenzo, Toninelli, Mariastella, Triggiani, Luca, Trinchieri, Alberto, Trodella, Luca Eolo, Trodella, Lucio, Trombetta, Carlo, Tronnolone, Lidia, Tucci, Marcello, Urzì, Daniele, Valdagni, Riccardo, Valeriani, Maurizio, Vanoli, Maurizio, Vitali, Elisabetta, Zaramella, Stefano, Zeccolini, Guglielmo, Zini, Giampaolo, Noale, Marianna (ORCID:0000-0002-4313-8427), Maggi, Stefania, D’Angelillo, Rolando, D’agostino, Daniele, Mantini, Giovanna (ORCID:0000-0001-5303-4499), Bassi, Pierfrancesco, Maggi, Ilaria Stefania, Artibani, Walter, Bassi, Pier Francesco, Bertoni, Filippo, Bracarda, Sergio, Conti, Giario Natale, Corvò, Renzo, Gacci, Mauro, Graziotti, Pierpaolo, Magrini, Stefano Maria, Maurizi Enrici, Riccardo, Mirone, Vincenzo, Montironi, Rodolfo, Muto, Giovanni, Pecoraro, Stefano, Porreca, Angelo, Ricardi, Umberto, Tubaro, Andrea, Zagonel, Vittorina, Zattoni, Filiberto, Crepaldi, Gaetano, Noale, Marianna, Alitto, Anna Rita, Ambrosi, Enrica, Antonelli, Alessandro, Aristei, Cynthia, Barbieri, Michele, Bardari, Franco, Bardoscia, Lilia, Barra, Salvina, Bartoncini, Sara, Basso, Umberto, Becherini, Carlotta, Bellavita, Rita, Bergamaschi, Franco, Berlingheri, Stefania, Berruti, Alfredo, Borghesi, Marco, Bortolus, Roberto, Borzillo, Valentina, Bosetti, Davide, Bove, Giuseppe, Bove, Pierluigi, Brausi, Maurizio, Bruni, Alessio, Baldari, Giorgio Bruno Cristiano, Brunocilla, Eugenio, Buffoli, Alberto, Buglione, Michela, Buttigliero, Consuelo, Cacciamani, Giovanni, Caldiroli, Michela, Cardo, Giuseppe, Carmignani, Giorgio, Carrieri, Giuseppe, Castelli, Emanuele, Castrezzati, Elisabetta, Catalano, Gianpiero, Cattarino, Susanna, Catucci, Francesco, Cavallini Francolini, Dario, Ceccarini, Ofelia, Celia, Antonio, Chiancone, Francesco, Chini, Tommaso, Cianci, Claudia, Cisternino, Antonio, Collura, Devi, Corbella, Franco, Corinti, Matteo, Corsi, Paolo, Cortese, Fiorenza, Corti, Luigi, de Nunzio, Cosimo, Cristiano, Olga, D'Angelillo, Rolando Maria, Da Pozzo, Luigi, D'Agostino, Daniele, D’Andrea, David, Dandrea, Matteo, De Angelis, Michele, De Cobelli, Ottavio, De Concilio, Bernardino, De Lisa, Antonello, De Luca, Stefano, De Stefani, Agostina, Deantoni, Chiara Lucrezia, Degli Esposti, Claudio, Destito, Anna, Detti, Beatrice, Di Muzio, Nadia, Di Stasio, Andrea, Di Stefano, Calogero, Di Trapani, Danilo, Difino, Giuseppe, Falivene, Sara, Farullo, Giuseppe, Fedelini, Paolo, Ferrari, Ilaria, Ferrau, Francesco, Ferro, Matteo, Fodor, Andrei, Fontana, Francesco, Francesca, Francesco, Giulio, Francolini, Frata, Paolo, Frezza, Giovanni, Gabriele, Pietro, Galeandro, Maria, Garibaldi, Ida Marina Elisabetta, Gennari, Pietro, Gentilucci, Alessandro, Giacobbe, Alessandro, Giussani, Laura, Giusti, Giuseppe, Gontero, Paolo, Guarneri, Alessia, Guida, Cesare, Gurioli, Alberto, Huqi, Dorijan, Imbimbo, Ciro, Ingrosso, Gianluca, Iotti, Cinzia, Italia, Corrado, La Mattina, Pierdaniele, Lamanna, Enza, Lastrucci, Luciana, Lazzari, Grazia, Liberale, Fabiola, Liguori, Giovanni, Lisi, Roberto, Lohr, Frank, Lombardo, Riccardo, Lovisolo, Jon, Ludovico, Giuseppe Mario, Macchione, Nicola, Maggio, Francesca, Malizia, Michele, Manasse, Gianluca, Mandoliti, Giovanni, Mantini, Giovanna, Marafioti, Luigi, Marciello, Luisa, Marconi, Alberto Mario, Martillotta, Antonietta, Marzano, Salvino, Masciullo, Stefano, Maso, Gloria, Massenzo, Adele, Mazzeo, Ercole, Mearini, Luigi, Medoro, Serena, Molè, Rosa, Monesi, Giorgio, Montanari, Emanuele, Montefiore, Franco, Montesi, Giampaolo, Morgia, Giuseppe, Moro, Gregorio, Muscas, Giorgio, Musio, Daniela, Muto, Paolo, Muzzonigro, Giovanni, Napodano, Giorgio, Negro, Carlo Luigi Augusto, Nidini, Mattia, Ntreta, Maria, Orsatti, Marco, Palazzolo, Carmela, Palumbo, Isabella, Parisi, Alessandro, Parma, Paolo, Pavan, Nicola, Pericolini, Martina, Pinto, Francesco, Pistone, Antonio, Pizzuti, Valerio, Platania, Angelo, Polli, Caterina, Pomara, Giorgio, Ponti, Elisabetta, Porcaro, Antonio Benito, Porpiglia, Francesco, Pugliese, Dario, Pycha, Armin, Raguso, Giuseppe, Rampini, Andrea, Randone, Donato Franco, Roscigno, Marco, Ruggieri, Maria Paola, Ruoppo, Giuseppe, Sanseverino, Roberto, Santacaterina, Anna, Santarsieri, Michele, Santoni, Riccardo, Scagliarini, Sarah, Scagliotti, Giorgio Vittorio, Scanzi, Mauro, Scarcia, Marcello, Schiavina, Riccardo, Sciarra, Alessandro, Sciorio, Carmine, Scolaro, Tindaro, Scuzzarella, Salvatore, Selvaggio, Oscar, Serao, Armando, Serni, Sergio, Signor, Marco Andrea, Silvani, Mauro, Silvano, Giovanni, Silvestris, Franco, Simeone, Claudio, Simone, Valeria, Spagnoletti, Girolamo, Spinelli, Matteo Giulio, Squillace, Luigi, Tombolini, Vincenzo, Toninelli, Mariastella, Triggiani, Luca, Trinchieri, Alberto, Trodella, Luca Eolo, Trodella, Lucio, Trombetta, Carlo, Tronnolone, Lidia, Tucci, Marcello, Urzì, Daniele, Valdagni, Riccardo, Valeriani, Maurizio, Vanoli, Maurizio, Vitali, Elisabetta, Zaramella, Stefano, Zeccolini, Guglielmo, Zini, Giampaolo, Noale, Marianna (ORCID:0000-0002-4313-8427), Maggi, Stefania, D’Angelillo, Rolando, D’agostino, Daniele, and Mantini, Giovanna (ORCID:0000-0001-5303-4499)

Abstract

Aims: The Pros-IT CNR project aims to monitor a sample of Italian males ≥18 years of age who have been diagnosed in the participating centers with incident prostate cancer, by analyzing their clinical features, treatment protocols and outcome results in relation to quality of life. Methods: Pros-IT CNR is an observational, prospective, multicenter study. The National Research Council (CNR), Neuroscience Institute, Aging Branch (Padua) is the promoting center. Ninety-seven Italian centers located throughout Italy were involved. The field study began in September 1, 2014. Subjects eligible were diagnosed with biopsy-verified prostate cancer, naà ̄ve. A sample size of 1500 patients was contemplated. A baseline assessment including anamnestic data, clinical history, risk factors, the initial diagnosis, cancer staging information and quality of life (Italian UCLA Prostate Cancer Index; SF-12 Scale) was completed. Six months after the initial diagnosis, a second assessment evaluating the patient’s health status, the treatment carried out, and the quality of life will be made. A third assessment, evaluating the treatment follow-up and the quality of life, will be made 12 months after the initial diagnosis. The 4th, 5th, 6th and 7th assessments, similar to the third, will be completed 24, 36, 48 and 60 months after the initial diagnosis, respectively, and will include also a Food Frequency Questionnaire and the Physical Activity Scale for the Elderly. Discussion: The study will provide information on patients’ quality of life and its variations over time in relation to the treatments received for the prostate cancer.

Published
2017

115. EP-1436: The superior vena cava syndrome (SVCS): role of the radiotherapy

Author

N.C. Natascia Costantino, A.D. Anna Destito, L.R.F. Lucia Rachele Fabiano, M.L. Marianna Lacaria, D.P. Domenicantonio Pingitore, M.S. Mariaquila Santoro, V.M. Vita Margheriti, and M.A.M. Maria Angela Molinaro

Subjects
Radiation therapy, medicine.medical_specialty, Superior vena cava syndrome, Oncology, business.industry, Radiology Nuclear Medicine and imaging, medicine.medical_treatment, Medicine, Radiology, Nuclear Medicine and imaging, Radiology, Hematology, medicine.symptom, business
Published
2016
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116. Management of Head and Neck Paragangliomas: A Series of 9 Cases and Review of the Literature

Author

Sebastiano Bucolo, Carmelo Quattrocchi, Alessandra Florio, and Domenico Destito

Subjects
Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Diagnosis, Differential, Paraganglioma, medicine.artery, medicine, Humans, Head and neck, Retrospective Studies, Paraganglioma, Extra-Adrenal, business.industry, Retrospective cohort study, Vagus Nerve Paraganglioma, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Surgery, Radiation therapy, Treatment Outcome, medicine.anatomical_structure, Otorhinolaryngology, Head and Neck Neoplasms, Population study, Female, Carotid body, Internal carotid artery, business
Abstract

We conducted a retrospective study of the long-term functional results of surgery for head and neck paragangliomas. Our study population was made up of 9 patients—4 men and 5 women, aged 22 to 59 years (mean: 46.6; median: 51)—who had undergone surgical excision of a head and neck paraganglioma from January 2002 through December 2006 in the ENT Department at Pugliese-Ciaccio Hospital in Catanzaro, Italy. Of the 9 paragangliomas, 4 were carotid body tumors, 2 were glomus tympanicum tumors, and 3 were glomus vagale tumors. None of the cases was bilateral or hereditary. Complete tumor resection was achieved in 8 patients; in the remaining patient, a small amount of intradural residual vagus nerve paraganglioma had to be left in situ. The internal carotid artery was preserved in all 4 resections of carotid body tumors. There was only 1 case of postoperative lower cranial nerve deficits, which occurred in a patient with a carotid body tumor. Follow-up ranged from 12 to 53 months (mean: 37.2; median: 36), and no recurrences were documented. Our small sample showed that surgical treatment of head and neck paragangliomas provided excellent tumor control with low postoperative morbidity, even in patients with large tumors. A wait-and-scan policy may be more appropriate for patients at an advanced age or who are otherwise at high surgical risk, as well as for those whose tumors have recurred following radiotherapy.

Published
2012

117. Interaction of cowpea mosaic virus nanoparticles with surface vimentin and inflammatory cells in atherosclerotic lesions

Author

Diane Thomas, Emily M. Plummer, Marianne Manchester, Leah P. Shriver, and Giuseppe Destito

Subjects
Male, Pathology, medicine.medical_specialty, viruses, Comovirus, Biomedical Engineering, Medicine (miscellaneous), Bioengineering, Vimentin, Development, Article, Cell Line, Lesion, Mice, medicine, Animals, Macrophage, General Materials Science, Cells, Cultured, Foam cell, biology, Macrophages, Cowpea mosaic virus, Endothelial Cells, Arteries, Atherosclerosis, biology.organism_classification, Ligand (biochemistry), Plaque, Atherosclerotic, In vitro, Lipoproteins, LDL, Mice, Inbred C57BL, Cell culture, biology.protein, Nanoparticles, medicine.symptom, Foam Cells
Abstract

Aims: Detection of atherosclerosis has generally been limited to the late stages of development, after cardiovascular symptoms present or a clinical event occurs. One possibility for early detection is the use of functionalized nanoparticles. The aim of this study was the early imaging of atherosclerosis using nanoparticles with a natural affinity for inflammatory cells in the lesion. Materials & methods: We investigated uptake of cowpea mosaic virus by macrophages and foam cells in vitro and correlated this with vimentin expression. We also examined the ability of cowpea mosaic virus to interact with atherosclerotic lesions in a murine model of atherosclerosis. Results & conclusion: We found that uptake of cowpea mosaic virus is increased in areas of atherosclerotic lesion. This correlated with increased surface vimentin in the lesion compared with nonlesion vasculature. In conclusion, cowpea mosaic virus and its vimentin-binding region holds potential for use as a targeting ligand for early atherosclerotic lesions, and as a probe for detecting upregulation of surface vimentin during inflammation. Original submitted 5 August 2011; Revised submitted 30 November 2011; Published online 6 March 2012

Published
2012

118. Correction to Discovery of the Hemifumarate and (α-<scp>l</scp>-Alanyloxy)methyl Ether as Prodrugs of an Antirheumatic Oxindole: Prodrugs for the Enolic OH Group

Author

Charles F Wright, Theodore E. Liston, Rosalina Destito, Alexander V. Kuperman, Lawrence A. Reiter, Kelvin Cooper, Deborah Malloy, Fiese Eugene F, Anthony Michael Campeta, David Young Mitchell, Wayne E. Barth, Sheri L. Shamblin, Fred C. Falkner, John J. Martin, Frank W. Rusek, Diane Lynn Johnson, Ralph P. Robinson, B. J. Cronin, and Kathleen M. Donahue

Subjects
Aqueous solution, Ether, Nuclear magnetic resonance spectroscopy, Prodrug, Chemical synthesis, Combinatorial chemistry, Bioavailability, chemistry.chemical_compound, chemistry, Drug Discovery, Molecular Medicine, Organic chemistry, Oxindole, Chemical stability
Abstract

Ether, ester, and carbonate derivatives of the antirheumatic oxindole 1 were prepared and screened as potential prodrugs of 1. This effort led to the discovery of the (alpha-L-alanyloxy)-methyl ether and hemifumarate derivatives of 1 which deliver the drug efficiently into the circulation of test animals, are stable in the solid state, and possess good stability in solution at low pH as required to ensure gastric stability. Success in achieving acceptable bioavailabilities of 1 across species (rats, dogs, and monkeys) followed the inclusion of ionizable functionality within the promoiety to compensate for masking the polar enolic OH group of the free drug. However, the introduction of ionizable functionality was often associated with decreased stability, as demonstrated by the hemisuccinate, hemiadipate, hemisuberate, and alpha-amino ester derivatives of 1 which could not be isolated. A clear exception was the hemifumarate derivative of 1 which was not only isolable but actually more stable at neutral pH than the nonionizable ester analogues. The solution and solid state stability of the hemifumarate, together with its activity as a prodrug of 1, suggests that hemifumarate be considered as an alternative to hemisuccinate as a prodrug derivative for alcohols, particularly in situations where solution state stability is an issue.

Published
2018

119. Investigational Drug Therapies for Overactive Bladder Syndrome: The Potential Alternatives to Anticolinergics

Author

A. Destito, Emilio Sacco, D. Tienforti, Francesco Pinto, Marco Racioppi, Francesco Marangi, Mario Gardi, Pierfrancesco Bassi, and A. Volpi

Subjects
0301 basic medicine, medicine.medical_specialty, Investigational drug, business.industry, Urology, Urinary incontinence, General Medicine, Disease, medicine.disease, Overactive bladder syndrome, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Pharmacotherapy, Quality of life (healthcare), Overactive bladder, medicine, medicine.symptom, Intensive care medicine, business, Medical therapy, 030217 neurology & neurosurgery
Abstract

Background Overactive bladder is a high prevalent and quality of life affecting disease. The mainstay of the medical therapy is represented by antimuscarinic drugs, but their side effects markedly affect patient compliance and prompt studies on novel investigational drugs. Methods A systematic literature search of peer-reviewed papers and meeting abstracts published by December 2008 was performed. PubMed databank was searched for original English articles, by using the following search terms: “overactive bladder” or “detrusor overactivity” or “urinary incontinence” and “treatment”, alone and linked to any potential molecular target or novel drug cited in the literature. Results Effective alternative pharmacological treatments are currently scarce, but many new promising compounds are emerging which target key molecular pathways involved in micturition control. The most promising potential therapeutic targets include central nervous system GABAergic inhibitory pathway, dopaminergic and serotoninergic systems, b-adrenoceptors and cAMP metabolism, nonadrenergic-noncholinergic mechanisms such as purinergic and neuropeptidergic systems, vanilloid receptor, bladder sensory nervous terminals, nonneuronal bladder signalling systems including urothelium and interstitial cells, prostanoids, Rho-kinase and different subtypes of potassium and calcium channels. Conclusions Despite the enormous amount of new biologic insight, very few novel pharmacological therapies seems to have passed the proof-of-concept clinical stage. The ultimate clinical utility of new drugs will depend on the ability to exploit tissue-specific differences and disease-related changes in molecular expression/function and to improve storage phase dysfunctions without interfering with the emptying phase. Further preclinical investigations and controlled clinical trials are urgently needed in this challenging field.

Published
2009

122. Correction: Generation and Improvement of Effector Function of a Novel Broadly Reactive and Protective Monoclonal Antibody against Pneumococcal Surface Protein A of Streptococcus pneumoniae

Author

Kristian, Sascha A., primary, Ota, Takayuki, additional, Bubeck, Sarah S., additional, Cho, Rebecca, additional, Groff, Brian C., additional, Kubota, Tsuguo, additional, Destito, Giuseppe, additional, Martin, Cécile, additional, Laudenslager, John, additional, Koriazova, Lilia, additional, Tahara, Tomoyuki, additional, and Kanda, Yutaka, additional

Published
2017
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123. Viral nanoparticles as tools for intravital vascular imaging

Author

Andries Zijlstra, Marianne Manchester, John D. Lewis, Giuseppe Destito, James P. Quigley, Heidi Stuhlmann, and Maria J. Gonzalez

Subjects
Diagnostic Imaging, Pathology, medicine.medical_specialty, Time Factors, Endothelium, Comovirus, Nanoparticle, Chick Embryo, Biology, Chorioallantoic Membrane, Article, General Biochemistry, Genetics and Molecular Biology, Polyethylene Glycols, Veins, Microcirculation, Neovascularization, Mice, In vivo, Neoplasms, medicine, Animals, Humans, Fluorescent Dyes, Tumor microenvironment, Neovascularization, Pathologic, Cowpea mosaic virus, Arteries, General Medicine, biology.organism_classification, Nanostructures, Chorioallantoic membrane, medicine.anatomical_structure, Biophysics, Endothelium, Vascular, medicine.symptom
Abstract

A significant impediment to the widespread use of noninvasive in vivo vascular imaging techniques is the current lack of suitable intravital imaging probes. We describe here a new strategy to use viral nanoparticles as a platform for the multivalent display of fluorescent dyes to image tissues deep inside living organisms. The bioavailable cowpea mosaic virus (CPMV) can be fluorescently labeled to high densities with no measurable quenching, resulting in exceptionally bright particles with in vivo dispersion properties that allow high-resolution intravital imaging of vascular endothelium for periods of at least 72 h. We show that CPMV nanoparticles can be used to visualize the vasculature and blood flow in living mouse and chick embryos to a depth of up to 500 microm. Furthermore, we show that the intravital visualization of human fibrosarcoma-mediated tumor angiogenesis using fluorescent CPMV provides a means to identify arterial and venous vessels and to monitor the neovascularization of the tumor microenvironment.

Published
2006

124. Sarcomatoid carcinoma of the adrenal gland: A case report and review of literature.

Author

Coli, A, Di Giorgio, A, Castri, F, Destito, C, Marin, Aw, Bigotti, G, Coli A (ORCID:0000-0001-6366-3993), Di Giorgio A, Castri F, Destito C, Bigotti G (ORCID:0000-0001-5065-2574), Coli, A, Di Giorgio, A, Castri, F, Destito, C, Marin, Aw, Bigotti, G, Coli A (ORCID:0000-0001-6366-3993), Di Giorgio A, Castri F, Destito C, and Bigotti G (ORCID:0000-0001-5065-2574)

Abstract

Reports about adrenocortical carcinomas (AC) mixed with sarcomatous areas are very rare. The terminology and pathogenesis of such biphasic tumors remain controversial. Herein, we report a case of sarcomatoid carcinoma of the adrenal gland in a 75-year-old woman who presented with left abdominal pain of one month's standing. The results of abdominal ultrasonography and computed tomography (CT) showed the presence of a large heterogeneous adrenal mass. A left adrenalectomy and complete splenectomy were performed. Histologically, the neoplasm showed areas of adrenocortical carcinoma and areas of sarcomatoid spindle cell proliferation. When examined immunohistochemically, the carcinomatous cells stained positively for S-100 protein, Melan-A protein, and neuron-specific enolase (NSE), and focally for vimentin and the cytokeratin marker MNF 116. Also, the carcinomatous cells were immunoreactive to the monoclonal antibody HMB-45. The sarcomatous component expressed vimentin, as well as other smooth and skeletal muscle markers. Liver metastases appeared 3 months postoperatively. Twelve months after removal of the primary tumor, the patient died of her disease. To the best of our knowledge, only seven cases of adrenal sarcomatoid carcinoma have been reported in the medical literature. We review the reported cases according to the 2004 classification of the World Health Organization (WHO) of lung tumors, and highlight the histogenesis, diagnosis, and clinical course of this very aggressive tumor.

Published
2010

125. A Soluble Receptor Decoy Protects Rats against Anthrax Lethal Toxin Challenge

Author

Giuseppe Destito, John A. T. Young, Darran J. Wigelsworth, R. John Collier, Marianne Manchester, Heather M. Scobie, Diane Thomas, and John M. Marlett

Subjects
Male, Time Factors, Receptors, Peptide, Anthrax toxin, Bacterial Toxins, CHO Cells, medicine.disease_cause, complex mixtures, Neutralization, Microbiology, Antigen, Cricetinae, medicine, Animals, Immunology and Allergy, Receptor, Antigens, Bacterial, biology, Toxin, fungi, Membrane Proteins, biology.organism_classification, Survival Analysis, Rats, Inbred F344, Rats, Bacillus anthracis, Infectious Diseases, Antitoxin, Bacteria, Protein Binding
Abstract

Successful postexposure treatment for inhalation anthrax is thought to include neutralization of anthrax toxin. The soluble anthrax toxin receptor/tumor endothelial marker 8 and capillary morphogenesis protein 2 (sATR/TEM8 and sCMG2, respectively) receptor decoys bind to anthrax toxin protective antigen (PA) and compete with cellular receptors for binding. Here, we show that, in a tissue-culture model of intoxication, sCMG2 is a 11.4-fold more potent antitoxin than sATR/TEM8 and that this increased activity corresponds to an approximately 1000-fold higher PA-binding affinity. Stoichiometric concentrations of sCMG2 protect rats against lethal toxin challenge, making sCMG2 one of the most effective anthrax antitoxins described to date.

Published
2005

126. Organic and Inorganic Nanoparticle Hybrids

Author

Anette Schneemann, Sumit Chaudhary, Krishna V. Singh, Mihrimah Ozkan, Nathaniel G. Portney, Marianne Manchester, and Giuseppe Destito

Subjects
Quantitative Biology::Biomolecules, Materials science, viruses, Comovirus, Nanoparticle, Mutagenesis (molecular biology technique), Nanotechnology, Surfaces and Interfaces, Conjugated system, Condensed Matter Physics, Quantitative Biology::Subcellular Processes, Capsid, Inorganic Chemicals, Quantum dot, Mutagenesis, Site-Directed, Electrochemistry, Quantitative Biology::Populations and Evolution, Nodaviridae, General Materials Science, Organic Chemicals, Nanoscopic scale, Spectroscopy
Abstract

Viruses are exemplary models in nanoassembly for their regular geometries, well characterized surface properties, and nanoscale dimensions. Armed with versatile tools aimed at site-directed mutagenesis to modify the virion's surface, conjugation chemistry for capsid coupling, and manipulation of nanoparticles, we have demonstrated nanoscale assembly of inorganic carbon nanotubes and quantum dots with engineered viruses to produce an intimate array of hybrid structures.

Published
2005

130. EP-1125: Survival, clinical response and prognostic factors in the reirradiation of recurrent brain tumors

Author

A.D. Anna Destito, L.R.F. Lucia Rachele Fabiano, A.S. Angela Saccomanno, M.S. Mariaquila Santoro, A.P. Armando Pingitore, M.L. Marianna Lacaria, E.M. Elvira Mazzei, R.M. Rosa Molè, M.A.M. Maria Angela Molinaro, L.P. Luigi Perrone, A.C. Angelo Chirillo, and D.P. DomenicantonioP ingitore

Subjects
Oncology, medicine.medical_specialty, business.industry, Radiology Nuclear Medicine and imaging, Internal medicine, Recurrent brain tumors, medicine, Radiology, Nuclear Medicine and imaging, Hematology, business
Published
2016
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131. EP-1083: Usefulness of PET/CT in definition of treatment volumes of head and neck tumors

Author

A.D. Anna Destito, M.S. Mariaquila Santoro, D.P. Domenicantonio Pingitore, R.M. Rosa Molè, L.P. Luigi Perrone, C.B. Cataldo Bianco, E.M. Elvira Mazzei, and M.A.M. Maria Angela Molinaro

Subjects
PET-CT, medicine.medical_specialty, Oncology, Radiology Nuclear Medicine and imaging, business.industry, Head and neck tumors, Medicine, Radiology, Nuclear Medicine and imaging, Hematology, Radiology, business
Published
2016

132. Abordaje translaberíntico para resección de neurinomas de gran tamaño y gigantes del nervio acústico

Author

D. Destito, A. Mincione, S. Righini, A. Falco Raucci, Roberto Pareschi, and S. Colombo

Subjects
medicine.medical_specialty, Otorhinolaryngology, Translabyrinthine approach, business.industry, Bone removal, medicine, ENT department, Nuclear medicine, business, Viiith nerve, Surgery
Abstract

The standard translabyrinthine approach for acoustic neuromas removal was introduced by W. House in 1964. After several years of experience the original translabyrinthine approach has been progressively modified into the current "enlarged" approach by extending the area of bone removal. This increased surgical field has made the translabyrinthine approach suitable for the removal of tumours of all sizes. We present our serie of 71 large (52) and giant (19) neuromas of the VIIIth nerve removed through a translabyrinthine approach between 1993 and 1998 at the ENT Department of Legnano.

Published
2002

136. GWAS of human bitter taste perception identifies new loci and reveals additional complexity of bitter taste genetics

Author

Amabilene Zamboni, Mirko Ledda, Sven Bergmann, Koichi Sameshima, Johannes le Coutre, Ulrich K. Genick, Jacques S. Beckmann, Zoltán Kutalik, Cintia A. Cirillo, Edgard Morya, Maria C. Souza Destito, Milena Monteiro de Souza, and Nathalie Martin

Subjects
Adult, Male, Taste, Adolescent, genetic structures, media_common.quotation_subject, Genome-wide association study, Biology, Coffee, Polymorphism, Single Nucleotide, Young Adult, Bitter taste perception, stomatognathic system, Perception, Genetics, medicine, Humans, SNP, Molecular Biology, Genetics (clinical), media_common, Quinine, Chromosomes, Human, Pair 12, Association Studies Articles, Genetic Variation, Reproducibility of Results, Taste Perception, General Medicine, Middle Aged, Bitter taste, TAS2R38, Genetic Loci, Female, Brazil, psychological phenomena and processes, Genome-Wide Association Study, medicine.drug
Abstract

Human perception of bitterness displays pronounced interindividual variation. This phenotypic variation is mirrored by equally pronounced genetic variation in the family of bitter taste receptor genes. To better understand the effects of common genetic variations on human bitter taste perception, we conducted a genome-wide association study on a discovery panel of 504 subjects and a validation panel of 104 subjects from the general population of São Paulo in Brazil. Correction for general taste-sensitivity allowed us to identify a SNP in the cluster of bitter taste receptors on chr12 (10.88- 11.24 Mb, build 36.1) significantly associated (best SNP: rs2708377, P = 5.31 × 10(-13), r(2) = 8.9%, β = -0.12, s.e. = 0.016) with the perceived bitterness of caffeine. This association overlaps with-but is statistically distinct from-the previously identified SNP rs10772420 influencing the perception of quinine bitterness that falls in the same bitter taste cluster. We replicated this association to quinine perception (P = 4.97 × 10(-37), r(2) = 23.2%, β = 0.25, s.e. = 0.020) and additionally found the effect of this genetic locus to be concentration specific with a strong impact on the perception of low, but no impact on the perception of high concentrations of quinine. Our study, thus, furthers our understanding of the complex genetic architecture of bitter taste perception.

Published
2014

137. Generation and Improvement of Effector Function of a Novel Broadly Reactive and Protective Monoclonal Antibody against Pneumococcal Surface Protein A of Streptococcus pneumoniae

Author

Kristian, Sascha A., primary, Ota, Takayuki, additional, Bubeck, Sarah S., additional, Cho, Rebecca, additional, Groff, Brian C., additional, Kubota, Tsuguo, additional, Destito, Giuseppe, additional, Laudenslager, John, additional, Koriazova, Lilia, additional, Tahara, Tomoyuki, additional, and Kanda, Yutaka, additional

Published
2016
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138. EP-1125: Survival, clinical response and prognostic factors in the reirradiation of recurrent brain tumors

Author

Mariaquila Santoro, M.S., primary, Maria Angela Molinaro, M.A.M., additional, Armando Pingitore, A.P., additional, Lucia Rachele Fabiano, L.R.F., additional, Angelo Chirillo, A.C., additional, Angela Saccomanno, A.S., additional, Luigi Perrone, L.P., additional, Marianna Lacaria, M.L., additional, Elvira Mazzei, E.M., additional, Rosa Molè, R.M., additional, Anna Destito, A.D., additional, and DomenicantonioP ingitore, D.P., additional

Published
2016
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139. EP-1445: The role of radiotherapy in the conservative treatment in bladder cancer elderly patients

Author

Mariaquila Santoro, M.S., primary, Maria Angela Molinaro, M.A.M., additional, Armando Pingitore, A.P., additional, Lucia Rachele Fabiano, L.R.F., additional, Angelo Chirillo, A.C., additional, Luigi Perrone, L.P., additional, Elvira Mazzei, E.M., additional, Angela Saccomanno, A.S., additional, Rosa Molè, R.M., additional, Anna Destito, A.D., additional, Marianna Lacaria, M.L., additional, and Domenicantonio Pingitore, D.P., additional

Published
2016
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144. Rinosinusite e allergia

Author

D'ANGELO, Luigi, SALZANO FA, SALERNO G, BUONGIORNO G, MANOLA M, DESTITO D, TRICARICO D, ABBAGNALE R., D'Angelo, Luigi, Salzano, Fa, Salerno, G, Buongiorno, G, Manola, M, Destito, D, Tricarico, D, and Abbagnale, R.

Published
2003

145. Contents Vol. 75, 2005

Author

Michael Alschibaja, F. Pinto, Wen-Chi Chen, Ömür Ataoğlu, Ayhan Verit, Jörg Massmann, Angelo Porreca, Ali Unsal, Giampaolo Delicato, Ming-Tsung Lai, Giulio Nicita, Destito A, Tahsin Turunc, Pierre Mongiat-Artus, John P. Gearhart, Muzaffer Eroğlu, Maria Cristina Paoletti, Aylin Kanli, Alessandro D'Addessi, N.S. Johal, Pranjal R Modi, Michele Marzocco, S.N. Jayasena, Francois Desgrandchamps, E. Crucitta, L. Apthorp, Fuu-Jen Tsai, Mete Kilciler, I.M. Tavolini, R.O. Plail, Chung-Hsiung Huang, S. Corvin, Hale Maral Kir, Mustafa Cengiz, Chih-Ming Lu, Eugenio Di Grazia, Rajiv Yadav, Anis Aribogan, Chao-I Wu, Marco Racioppi, Stéphane Milcent, Wolfgang Sturm, Meng-Chu Chung, Fikret Erdemir, Surendra B. Kolla, Dominic Frimberger, Yasar Ozgok, M. Zucchetti, C. Kouriefs, L. Managadze, Zaza Mezvrishvili, Roger Paul, Maria Teresa Filocamo, Oguz Acar, Gagan Gautam, Meltem Ozlen Dillioglugil, Rajiv Goel, D.M.R. Gunawardena, Markus A. Kuczyk, Ersin Çimentepe, V. De Marco, Koray Erten, Armin Funk, M. Derya Balbay, Sharad Dodia, Monish Aron, Jean Marc Duclos, Ercan Yeni, Ashok K. Hemal, Hasan Bakırtaş, Lei Wan, M. V. C. De Silva, Ying-Chin Ko, Donata Villari, Selahattin Bedir, Dario Nicolosi, Aristotelis G. Anastasiadis, Dogan Unal, Rudolf Hartung, F. Longo, Atilla Aridogan, J.T.N. Ariyasinghe, Pierre Teillac, Nazario Foschi, Mathias Wegner, Hsi-Chin Wu, Paul Meria, L. Marini, Hacı Kahya Ozdogan, P. Bassi, S.A.S. Gunawardena, Sule Akin, F. Dal Moro, E. Dattolo, Arnulf Stenzl, Narmada P. Gupta, Vincenzo Li Marzi, Onder Ors, Huey-Yi Chen, Ozdal Dillioglugil, Mehmet Doğan Gülkaç, and Hidayet Coban

Subjects
Traditional medicine, business.industry, Urology, Medicine, business
Published
2005

147. Concurrent and orthogonal gold(I) and ruthenium (II) catalysis inside living cells.

Author

Vidal, Cristian, Tomás-Gamas, María, Destito, Paolo, López, Fernando, and Mascareñas, José L.

Abstract

The viability of building artificial metabolic pathways within a cell will depend on our ability to design biocompatible and orthogonal catalysts capable of achieving non-natural transformations. In this context, transition metal complexes offer unique possibilities to develop catalytic reactions that do not occur in nature. However, translating the potential of metal catalysts to living cells poses numerous challenges associated to their biocompatibility, and their stability and reactivity in crowded aqueous environments. Here we report a gold-mediated C-C bond formation that occurs in complex aqueous habitats, and demonstrate that the reaction can be translated to living mammalian cells. Key to the success of the process is the use of designed, water-activatable gold chloride complexes. Moreover, we demonstrate the viability of achieving the gold-promoted process in parallel with a ruthenium-mediated reaction, inside living cells, and in a bioorthogonal and mutually orthogonal manner. [ABSTRACT FROM AUTHOR]

Published
2018
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148. Discovery of the Hemifumarate and (α-<scp>l</scp>-Alanyloxy)methyl Ether as Prodrugs of an Antirheumatic Oxindole: Prodrugs for the Enolic OH Group

Author

R P, Robinson, L A, Reiter, W E, Barth, A M, Campeta, K, Cooper, B J, Cronin, R, Destito, K M, Donahue, F C, Falkner, E F, Fiese, D L, Johnson, A V, Kuperman, T E, Liston, D, Malloy, J J, Martin, D Y, Mitchell, F W, Rusek, S L, Shamblin, and C F, Wright

Subjects
Indoles, Magnetic Resonance Spectroscopy, Molecular Structure, Anti-Inflammatory Agents, Non-Steroidal, Maleates, Biological Availability, Rats, Rats, Sprague-Dawley, Macaca fascicularis, Dogs, Fumarates, Drug Discovery, Animals, Molecular Medicine, Prodrugs, Ethers
Abstract

Ether, ester, and carbonate derivatives of the antirheumatic oxindole 1 were prepared and screened as potential prodrugs of 1. This effort led to the discovery of the (alpha-L-alanyloxy)-methyl ether and hemifumarate derivatives of 1 which deliver the drug efficiently into the circulation of test animals, are stable in the solid state, and possess good stability in solution at low pH as required to ensure gastric stability. Success in achieving acceptable bioavailabilities of 1 across species (rats, dogs, and monkeys) followed the inclusion of ionizable functionality within the promoiety to compensate for masking the polar enolic OH group of the free drug. However, the introduction of ionizable functionality was often associated with decreased stability, as demonstrated by the hemisuccinate, hemiadipate, hemisuberate, and alpha-amino ester derivatives of 1 which could not be isolated. A clear exception was the hemifumarate derivative of 1 which was not only isolable but actually more stable at neutral pH than the nonionizable ester analogues. The solution and solid state stability of the hemifumarate, together with its activity as a prodrug of 1, suggests that hemifumarate be considered as an alternative to hemisuccinate as a prodrug derivative for alcohols, particularly in situations where solution state stability is an issue.

Published
1996

149. EP-1324: High risk early stage endometrial cancer: lymphadenectomy with brachytherapy as alternative to EBRT

Author

M.S. Mariaquila Santoro, R.L. Fabiano, E.M. Elvira Mazzei, Cataldo Bianco, M.A.M. Maria Angela Molinaro, A.D. Anna Destito, R.M. Rosa Molè, and D.P. Domenicantonio Pingitore

Subjects
Oncology, medicine.medical_specialty, business.industry, Endometrial cancer, medicine.medical_treatment, Brachytherapy, Hematology, medicine.disease, Radiology Nuclear Medicine and imaging, Internal medicine, Medicine, Radiology, Nuclear Medicine and imaging, Lymphadenectomy, Stage (cooking), business
Published
2016

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