Search

Your search keyword '"Ciotti, M."' showing total 9 results
Start Over Author "Ciotti, M." Publication Type Electronic Resources
9 results on '"Ciotti, M."'

1. Physics basis for the divertor tokamak test facility

Author

Crisanti, F, Ambrosino, R, Falessi, M, Gabellieri, L, Giruzzi, G, Granucci, G, Innocente, P, Mantica, P, Ramogida, G, Vlad, G, Albanese, R, Alessi, E, Angioni, C, Agostinetti, P, Aucone, L, Auriemma, F, Baiocchi, B, Balbinot, L, Balestri, A, Barberis, T, Baruzzo, M, Bolzonella, T, Bonanomi, N, Bonfiglio, D, Brezinsek, S, Calabro, G, Cani, F, Casiraghi, I, Castaldo, A, Castaldo, C, Cavedon, M, Ceccuzzi, S, Cichocki, F, Ciotti, M, Day, C, De Piccoli, C, Dose, G, Emanueli, E, Frassinetti, L, Figini, L, Fusco, V, Giovannozzi, E, Gobbin, M, Koechi, F, Kryzhanovskyy, A, Li, Y, Lombroni, R, Luda, T, Mariani, A, Martin, P, Meineri, C, Murari, A, Muscente, P, Napoli, F, Nardon, E, Neu, R, Nocente, M, Notazio, M, Nowak, S, Pigatto, L, Piron, C, Porcelli, F, Roccella, S, Rubino, G, Scarpari, M, Sozzi, C, Spizzo, G, Subba, F, Taccogna, F, Tantos, C, Terranova, D, Tsitrone, E, Uccello, A, Van Eester, D, Vianello, N, Vincenzi, P, Wischmeier, M, Zonca, F, Crisanti F., Ambrosino R., Falessi M. V., Gabellieri L., Giruzzi G., Granucci G., Innocente P., Mantica P., Ramogida G., Vlad G., Albanese R., Alessi E., Angioni C., Agostinetti P., Aucone L., Auriemma F., Baiocchi B., Balbinot L., Balestri A., Barberis T., Baruzzo M., Bolzonella T., Bonanomi N., Bonfiglio D., Brezinsek S., Calabro G., Cani F., Casiraghi I., Castaldo A., Castaldo C., Cavedon M., Ceccuzzi S., Cichocki F., Ciotti M., Day C., De Piccoli C., Dose G., Emanueli E., Frassinetti L., Figini L., Fusco V., Giovannozzi E., Gobbin M., Koechi F., Kryzhanovskyy A., Li Y., Lombroni R., Luda T., Mariani A., Martin P., Meineri C., Murari A., Muscente P., Napoli F., Nardon E., Neu R., Nocente M., Notazio M., Nowak S., Pigatto L., Piron C., Porcelli F., Roccella S., Rubino G., Scarpari M., Sozzi C., Spizzo G., Subba F., Taccogna F., Tantos C., Terranova D., Tsitrone E., Uccello A., Van Eester D., Vianello N., Vincenzi P., Wischmeier M., Zonca F., Crisanti, F, Ambrosino, R, Falessi, M, Gabellieri, L, Giruzzi, G, Granucci, G, Innocente, P, Mantica, P, Ramogida, G, Vlad, G, Albanese, R, Alessi, E, Angioni, C, Agostinetti, P, Aucone, L, Auriemma, F, Baiocchi, B, Balbinot, L, Balestri, A, Barberis, T, Baruzzo, M, Bolzonella, T, Bonanomi, N, Bonfiglio, D, Brezinsek, S, Calabro, G, Cani, F, Casiraghi, I, Castaldo, A, Castaldo, C, Cavedon, M, Ceccuzzi, S, Cichocki, F, Ciotti, M, Day, C, De Piccoli, C, Dose, G, Emanueli, E, Frassinetti, L, Figini, L, Fusco, V, Giovannozzi, E, Gobbin, M, Koechi, F, Kryzhanovskyy, A, Li, Y, Lombroni, R, Luda, T, Mariani, A, Martin, P, Meineri, C, Murari, A, Muscente, P, Napoli, F, Nardon, E, Neu, R, Nocente, M, Notazio, M, Nowak, S, Pigatto, L, Piron, C, Porcelli, F, Roccella, S, Rubino, G, Scarpari, M, Sozzi, C, Spizzo, G, Subba, F, Taccogna, F, Tantos, C, Terranova, D, Tsitrone, E, Uccello, A, Van Eester, D, Vianello, N, Vincenzi, P, Wischmeier, M, Zonca, F, Crisanti F., Ambrosino R., Falessi M. V., Gabellieri L., Giruzzi G., Granucci G., Innocente P., Mantica P., Ramogida G., Vlad G., Albanese R., Alessi E., Angioni C., Agostinetti P., Aucone L., Auriemma F., Baiocchi B., Balbinot L., Balestri A., Barberis T., Baruzzo M., Bolzonella T., Bonanomi N., Bonfiglio D., Brezinsek S., Calabro G., Cani F., Casiraghi I., Castaldo A., Castaldo C., Cavedon M., Ceccuzzi S., Cichocki F., Ciotti M., Day C., De Piccoli C., Dose G., Emanueli E., Frassinetti L., Figini L., Fusco V., Giovannozzi E., Gobbin M., Koechi F., Kryzhanovskyy A., Li Y., Lombroni R., Luda T., Mariani A., Martin P., Meineri C., Murari A., Muscente P., Napoli F., Nardon E., Neu R., Nocente M., Notazio M., Nowak S., Pigatto L., Piron C., Porcelli F., Roccella S., Rubino G., Scarpari M., Sozzi C., Spizzo G., Subba F., Taccogna F., Tantos C., Terranova D., Tsitrone E., Uccello A., Van Eester D., Vianello N., Vincenzi P., Wischmeier M., and Zonca F.

Abstract

This paper is dealing with the physics basis used for the design of the Divertor Tokamak Test facility (DTT), under construction in Frascati (DTT 2019 DTT interim design report (2019)) Italy, and with the description of the main target plasma scenarios of the device. The main goal of the facility will be the study of the power exhaust, intended as a fully integrated core-edge problem, and eventually to propose an optimized divertor for the European DEMO plant. The approach used to design the facility is described and their main features are reported, by using simulations performed by state-of-the-art codes both for the bulk and edge studies. A detailed analysis of MHD, including also the possibility to study disruption events and Energetic Particles physics is also reported. Eventually, a description of the ongoing work to build-up a Research Plan written and shared by the full EUROfusion community is presented.

Published
2024

2. Community engagement in public health emergency preparedness

Author

Takacs, J., Ciotti, M., Tsolova, S., Wiltshire, E., Baka, A., Kinsman, John, de Vries, D., Cremers, L., Rios, M., Angren, J., Takacs, J., Ciotti, M., Tsolova, S., Wiltshire, E., Baka, A., Kinsman, John, de Vries, D., Cremers, L., Rios, M., and Angren, J.

Abstract

Background Communities that could be affected by infectious disease outbreaks are increasingly recognised as resources that may be effectively utilized by the authorities during public health emergencies. Methods This case study project, aiming to identify synergies between communities and authorities, was based on qualitative sources of evidence, including document and media review, stakeholder mapping, interviews and FGDs (N = 137). Four countries were selected for inclusion: Spain and the Netherlands on the basis of emerging tick-born disease incidents; Iceland and Ireland on the basis of acute gastroenteritis outbreaks. Results In the Netherlands and Spain strong synergies were identified in tick surveillance activities, and the value of pre-existing networks of interest groups for preparedness and response activities was recognised. The Icelandic norovirus event was unexpected and fast-moving, while VTEC in Ireland is a familiar and slower-burning challenge. As a relatively common disease in Ireland, VTEC-protocols are closely followed, while a generic all-hazards approach was taken in Iceland. There was considerable community support in the responses in both countries., and in Iceland community representatives also actively participated in producing institutional post-event evaluations. Conclusions An over-riding principle emerging from this study is that an informed, at-risk community understands the challenges to adopting effective preventive practices for themselves better than anyone. Additional good practices included the utilisation of pre-existing stakeholder networks for information dissemination; and of monitoring community perceptions of any public health incident, including through social media, in order to identify and manage misperceptions. Efforts to build on the community engagement activities that are already in place in the four countries could contribute to better preparedness planning and more efficient and timely responses in future outbrea

Published
2019
Full Text
View/download PDF

3. The medial septum is insulin resistant in the AD presymptomatic phase: rescue by nerve growth factor-driven IRS1 activation.

Author

Sposato, V., Canu, N., Fico, E., Fusco, Salvatore, Bolasco, G., Ciotti, M. T., Spinelli, Matteo, Mercanti, D., Grassi, Claudio, Triaca, V., Calissano, P., Fusco S. (ORCID:0000-0003-3294-0016), Spinelli M., Grassi C. (ORCID:0000-0001-7253-1685), Sposato, V., Canu, N., Fico, E., Fusco, Salvatore, Bolasco, G., Ciotti, M. T., Spinelli, Matteo, Mercanti, D., Grassi, Claudio, Triaca, V., Calissano, P., Fusco S. (ORCID:0000-0003-3294-0016), Spinelli M., and Grassi C. (ORCID:0000-0001-7253-1685)

Abstract

Basal forebrain cholinergic neurons (BFCN) are key modulators of learning and memory and are high energy-demanding neurons. Impaired neuronal metabolism and reduced insulin signaling, known as insulin resistance, has been reported in the early phase of Alzheimer's disease (AD), which has been suggested to be "Type 3 Diabetes." We hypothesized that BFCN may develop insulin resistance and their consequent failure represents one of the earliest event in AD. We found that a condition reminiscent of insulin resistance occurs in the medial septum of 3 months old 3×Tg-AD mice, reported to develop typical AD histopathology and cognitive deficits in adulthood. Further, we obtained insulin resistant BFCN by culturing them with high insulin concentrations. By means of these paradigms, we observed that nerve growth factor (NGF) reduces insulin resistance in vitro and in vivo. NGF activates the insulin receptor substrate 1 (IRS1) and rescues c-Fos expression and glucose metabolism. This effect involves binding of activated IRS1 to the NGF receptor TrkA, and is lost in presence of the specific IRS inhibitor NT157. Overall, our findings indicate that, in a well-established animal model of AD, the medial septum develops insulin resistance several months before it is detectable in the neocortex and hippocampus. Remarkably, NGF counteracts molecular alterations downstream of insulin-resistant receptor and its nasal administration restores insulin signaling in 3×Tg-AD mice by TrkA/IRS1 activation. The cross-talk between NGF and insulin pathways downstream the insulin receptor suggests novel potential therapeutic targets to slow cognitive decline in AD and diabetes-related brain insulin resistance.

Published
2019

4. HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels

Author

Di Maio, V, Cento, V, Di Paolo, D, Aragri, M, De Leonardis, F, Tontodonati, M, Micheli, V, Bellocchi, M, Antonucci, F, Bertoli, A, Lenci, I, Milana, M, Gianserra, L, Melis, M, Di Biagio, A, Sarrecchia, C, Sarmati, L, Landonio, S, Francioso, S, Lambiase, L, Nicolini, L, Marenco, S, Nosotti, L, Giannelli, V, Siciliano, M, Romagnoli, D, Pellicelli, A, Vecchiet, J, Magni, C, Babudieri, S, Mura, M, Taliani, G, Mastroianni, C, Vespasiani-Gentilucci, U, Romano, M, Morisco, F, Gasbarrini, A, Vullo, V, Bruno, S, Baiguera, C, Pasquazzi, C, Tisone, G, Picciotto, A, Andreoni, M, Parruti, G, Rizzardini, G, Angelico, M, Perno, C, Ceccherini-Silberstein, F, Mariani, R, Paoloni, M, Iapadre, N, Grimaldi, A, Menzaghi, B, Quirino, T, Bruzzone, B, De Maria, A, Viscoli, C, Casinelli, K, Delle Monache, M, Lichtner, M, Aghemo, A, Cerrone, M, Colombo, M, D'Arminio Monforte, A, Danieli, E, Donato, F, Gubertini, G, Mancon, A, Monico, S, Niero, F, Puoti, M, Russo, M, Alfieri, R, Gnocchi, M, Orro, A, Milanesi, L, Baldelli, E, Bertolotti, M, Borghi, V, Mussini, C, Brancaccio, G, Caporaso, N, Gaeta, G, Lembo, V, Calvaruso, V, Craxi, A, Di Marco, V, Mazzola, A, Petta, S, D'Amico, E, Cacciatore, P, Consorte, A, Pace Palitti, V, Pieri, A, Polilli, E, Antenucci, F, Armenia, D, Baiocchi, L, Biliotti, E, Biolato, M, Carioti, L, Cerasari, G, Cerva, C, Ciotti, M, D'Ambrosio, C, D'Ettorre, G, De Sanctis, A, Furlan, C, Gallo, P, Grieco, A, Grieco, S, Lattanzi, B, Malagnino, V, Manuelli, M, Merli, M, Miglioresi, L, Palazzo, D, Santopaolo, F, Santoro, M, Sforza, D, Sorbo, M, Spaziante, M, Svicher, V, Teti, E, Mangia, A, Maida, I, Falconi, L, Di Giammartino, D, Tarquini, P, Di Maio V. C., Cento V., Di Paolo D., Aragri M., De Leonardis F., Tontodonati M., Micheli V., Bellocchi M. C., Antonucci F. P., Bertoli A., Lenci I., Milana M., Gianserra L., Melis M., Di Biagio A., Sarrecchia C., Sarmati L., Landonio S., Francioso S., Lambiase L., Nicolini L. A., Marenco S., Nosotti L., Giannelli V., Siciliano M., Romagnoli D., Pellicelli A., Vecchiet J., Magni C. F., Babudieri S., Mura M. S., Taliani G., Mastroianni C., Vespasiani-Gentilucci U., Romano M., Morisco F., Gasbarrini A., Vullo V., Bruno S., Baiguera C., Pasquazzi C., Tisone G., Picciotto A., Andreoni M., Parruti G., Rizzardini G., Angelico M., Perno C. F., Ceccherini-Silberstein F., Mariani R., Paoloni M., Iapadre N., Grimaldi A., Menzaghi B., Quirino T., Bruzzone B., De Maria A., Viscoli C., Casinelli K., Delle Monache M., Lichtner M., Aghemo A., Cerrone M., Colombo M., D'Arminio Monforte A., Danieli E., Donato F., Gubertini G., Mancon A., Monico S., Niero F., Puoti M., Russo M. L., Alfieri R., Gnocchi M., Orro A., Milanesi L., Baldelli E., Bertolotti M., Borghi V., Mussini C., Brancaccio G., Caporaso N., Gaeta G. B., Lembo V., Calvaruso V., Craxi A., Di Marco V., Mazzola A., Petta S., D'Amico E., Cacciatore P., Consorte A., Pace Palitti V., Pieri A., Polilli E., Antenucci F., Armenia D., Baiocchi L., Biliotti E., Biolato M., Carioti L., Cerasari G., Cerva C., Ciotti M., D'Ambrosio C., D'Ettorre G., De Sanctis A., Furlan C., Gallo P., Grieco A., Grieco S., Lattanzi B., Malagnino V., Manuelli M., Merli M., Miglioresi L., Palazzo D., Santopaolo F., Santoro M. M., Sforza D., Sorbo M. C., Spaziante M., Svicher V., Teti E., Mangia A., Maida I., Falconi L., Di Giammartino D., Tarquini P., Di Maio, V, Cento, V, Di Paolo, D, Aragri, M, De Leonardis, F, Tontodonati, M, Micheli, V, Bellocchi, M, Antonucci, F, Bertoli, A, Lenci, I, Milana, M, Gianserra, L, Melis, M, Di Biagio, A, Sarrecchia, C, Sarmati, L, Landonio, S, Francioso, S, Lambiase, L, Nicolini, L, Marenco, S, Nosotti, L, Giannelli, V, Siciliano, M, Romagnoli, D, Pellicelli, A, Vecchiet, J, Magni, C, Babudieri, S, Mura, M, Taliani, G, Mastroianni, C, Vespasiani-Gentilucci, U, Romano, M, Morisco, F, Gasbarrini, A, Vullo, V, Bruno, S, Baiguera, C, Pasquazzi, C, Tisone, G, Picciotto, A, Andreoni, M, Parruti, G, Rizzardini, G, Angelico, M, Perno, C, Ceccherini-Silberstein, F, Mariani, R, Paoloni, M, Iapadre, N, Grimaldi, A, Menzaghi, B, Quirino, T, Bruzzone, B, De Maria, A, Viscoli, C, Casinelli, K, Delle Monache, M, Lichtner, M, Aghemo, A, Cerrone, M, Colombo, M, D'Arminio Monforte, A, Danieli, E, Donato, F, Gubertini, G, Mancon, A, Monico, S, Niero, F, Puoti, M, Russo, M, Alfieri, R, Gnocchi, M, Orro, A, Milanesi, L, Baldelli, E, Bertolotti, M, Borghi, V, Mussini, C, Brancaccio, G, Caporaso, N, Gaeta, G, Lembo, V, Calvaruso, V, Craxi, A, Di Marco, V, Mazzola, A, Petta, S, D'Amico, E, Cacciatore, P, Consorte, A, Pace Palitti, V, Pieri, A, Polilli, E, Antenucci, F, Armenia, D, Baiocchi, L, Biliotti, E, Biolato, M, Carioti, L, Cerasari, G, Cerva, C, Ciotti, M, D'Ambrosio, C, D'Ettorre, G, De Sanctis, A, Furlan, C, Gallo, P, Grieco, A, Grieco, S, Lattanzi, B, Malagnino, V, Manuelli, M, Merli, M, Miglioresi, L, Palazzo, D, Santopaolo, F, Santoro, M, Sforza, D, Sorbo, M, Spaziante, M, Svicher, V, Teti, E, Mangia, A, Maida, I, Falconi, L, Di Giammartino, D, Tarquini, P, Di Maio V. C., Cento V., Di Paolo D., Aragri M., De Leonardis F., Tontodonati M., Micheli V., Bellocchi M. C., Antonucci F. P., Bertoli A., Lenci I., Milana M., Gianserra L., Melis M., Di Biagio A., Sarrecchia C., Sarmati L., Landonio S., Francioso S., Lambiase L., Nicolini L. A., Marenco S., Nosotti L., Giannelli V., Siciliano M., Romagnoli D., Pellicelli A., Vecchiet J., Magni C. F., Babudieri S., Mura M. S., Taliani G., Mastroianni C., Vespasiani-Gentilucci U., Romano M., Morisco F., Gasbarrini A., Vullo V., Bruno S., Baiguera C., Pasquazzi C., Tisone G., Picciotto A., Andreoni M., Parruti G., Rizzardini G., Angelico M., Perno C. F., Ceccherini-Silberstein F., Mariani R., Paoloni M., Iapadre N., Grimaldi A., Menzaghi B., Quirino T., Bruzzone B., De Maria A., Viscoli C., Casinelli K., Delle Monache M., Lichtner M., Aghemo A., Cerrone M., Colombo M., D'Arminio Monforte A., Danieli E., Donato F., Gubertini G., Mancon A., Monico S., Niero F., Puoti M., Russo M. L., Alfieri R., Gnocchi M., Orro A., Milanesi L., Baldelli E., Bertolotti M., Borghi V., Mussini C., Brancaccio G., Caporaso N., Gaeta G. B., Lembo V., Calvaruso V., Craxi A., Di Marco V., Mazzola A., Petta S., D'Amico E., Cacciatore P., Consorte A., Pace Palitti V., Pieri A., Polilli E., Antenucci F., Armenia D., Baiocchi L., Biliotti E., Biolato M., Carioti L., Cerasari G., Cerva C., Ciotti M., D'Ambrosio C., D'Ettorre G., De Sanctis A., Furlan C., Gallo P., Grieco A., Grieco S., Lattanzi B., Malagnino V., Manuelli M., Merli M., Miglioresi L., Palazzo D., Santopaolo F., Santoro M. M., Sforza D., Sorbo M. C., Spaziante M., Svicher V., Teti E., Mangia A., Maida I., Falconi L., Di Giammartino D., and Tarquini P.

Abstract

Objectives: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. Methods: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. Results: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA > 3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤ 3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). Conclusions: HCV-NS3 sequencing provides reliable

Published
2016

5. HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels

Author

Di Maio, V. C., Centomini, Vanna, Di Paolo, D., Aragri, M., De Leonardis, F., Tontodonati, M., Micheli, V., Bellocchi, M. C., Antonucci, F. P., Bertoli, Alessia, Lenci, I., Milana, M., Gianserra, L., Milan, Melissa, Di Biagio, Anna, Sarrecchia, C., Sarmati, L., Landonio, S., Francioso, S., Lambiase, L., Nicolini, L. A., Marenco, S., Nosotti, L., Giannelli, V., Siciliano, Massimo, Romagnoli, D., Pellicelli, A., Vecchiet, J., Magni, C. F., Babudieri, S., Mura, M. S., Taliani, G., Mastroianni, C., Vespasiani-Gentilucci, U., Romano, M., Morisco, F., Gasbarrini, Antonio, Vullo, V., Bruno, S., Baiguera, C., Pasquazzi, C., Tisone, G., Picciotto, A., Andreoni, M., Parruti, G., Rizzardini, G., Angelico, M., Perno, C. F., Ceccherini-Silberstein, F., Mariani, R., Paoloni, M., Iapadre, N., Grimaldi, A., Menzaghi, B., Quirino, T., Bruzzone, B., De Maria, A., Viscoli, C., Casinelli, K., Delle Monache, M., Lichtner, M., Aghemo, A., Cerrone, M., Colombo, M., D'Arminio Monforte, A., Danieli, E., Donato, Federica, Gubertini, G., Mancon, A., Monico, S., Niero, F., Puoti, M., Russo, M. L., Alfieri, R., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Brancaccio, G., Caporaso, N., Gaeta, G. B., Lembo, V., Calvaruso, V., Craxí, A., Di Marco, V., Mazzola, A., Petta, S., D'Amico, E., Cacciatore, Pasquale, Consorte, A., Pace Palitti, V., Pieri, A., Polilli, E., Antenucci, F., Armenia, D., Baiocchi, L., Bellocchi, M., Biliotti, E., Biolato, Marco, Carioti, L., Cerasari, G., Cerva, C., Ciotti, M., D'Ambrosio, C., D'Ettorre, G., De Sanctis, A., Furlan, C., Gallo, P., Grieco, Antonio, Grieco, S., Lattanzi, B., Malagnino, V., Manuelli, M., Merli, M., Miglioresi, L., Palazzo, D., Santopaolo, F., Santoro, M. M., Sforza, D., Siciliano, M., Sorbo, M. C., Spaziante, M., Svicher, V., Teti, E., Mangia, A., Maida, I., Falconi, L., Di Giammartino, D., Tarquini, P., Cento, V., Bertoli, A., Melis, M., Di Biagio, A., Gasbarrini, A. (ORCID:0000-0002-7278-4823), Donato, F., Cacciatore, P., Biolato, M., Grieco, A. (ORCID:0000-0002-0544-8993), Di Maio, V. C., Centomini, Vanna, Di Paolo, D., Aragri, M., De Leonardis, F., Tontodonati, M., Micheli, V., Bellocchi, M. C., Antonucci, F. P., Bertoli, Alessia, Lenci, I., Milana, M., Gianserra, L., Milan, Melissa, Di Biagio, Anna, Sarrecchia, C., Sarmati, L., Landonio, S., Francioso, S., Lambiase, L., Nicolini, L. A., Marenco, S., Nosotti, L., Giannelli, V., Siciliano, Massimo, Romagnoli, D., Pellicelli, A., Vecchiet, J., Magni, C. F., Babudieri, S., Mura, M. S., Taliani, G., Mastroianni, C., Vespasiani-Gentilucci, U., Romano, M., Morisco, F., Gasbarrini, Antonio, Vullo, V., Bruno, S., Baiguera, C., Pasquazzi, C., Tisone, G., Picciotto, A., Andreoni, M., Parruti, G., Rizzardini, G., Angelico, M., Perno, C. F., Ceccherini-Silberstein, F., Mariani, R., Paoloni, M., Iapadre, N., Grimaldi, A., Menzaghi, B., Quirino, T., Bruzzone, B., De Maria, A., Viscoli, C., Casinelli, K., Delle Monache, M., Lichtner, M., Aghemo, A., Cerrone, M., Colombo, M., D'Arminio Monforte, A., Danieli, E., Donato, Federica, Gubertini, G., Mancon, A., Monico, S., Niero, F., Puoti, M., Russo, M. L., Alfieri, R., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Brancaccio, G., Caporaso, N., Gaeta, G. B., Lembo, V., Calvaruso, V., Craxí, A., Di Marco, V., Mazzola, A., Petta, S., D'Amico, E., Cacciatore, Pasquale, Consorte, A., Pace Palitti, V., Pieri, A., Polilli, E., Antenucci, F., Armenia, D., Baiocchi, L., Bellocchi, M., Biliotti, E., Biolato, Marco, Carioti, L., Cerasari, G., Cerva, C., Ciotti, M., D'Ambrosio, C., D'Ettorre, G., De Sanctis, A., Furlan, C., Gallo, P., Grieco, Antonio, Grieco, S., Lattanzi, B., Malagnino, V., Manuelli, M., Merli, M., Miglioresi, L., Palazzo, D., Santopaolo, F., Santoro, M. M., Sforza, D., Siciliano, M., Sorbo, M. C., Spaziante, M., Svicher, V., Teti, E., Mangia, A., Maida, I., Falconi, L., Di Giammartino, D., Tarquini, P., Cento, V., Bertoli, A., Melis, M., Di Biagio, A., Gasbarrini, A. (ORCID:0000-0002-7278-4823), Donato, F., Cacciatore, P., Biolato, M., and Grieco, A. (ORCID:0000-0002-0544-8993)

Abstract

Objectives: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. Methods: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. Results: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA > 3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤ 3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). Conclusions: HCV-NS3 sequencing provides reliable

Published
2016

6. HPV-associated lung cancers: An international pooled analysis

Author

Ragin, C. Obikoya-Malomo, M. Kim, S. Chen, Z. Flores-Obando, R. Gibbs, D. Koriyama, C. Aguayo, F. Koshiol, J. Caporaso, N.E. Carpagnano, G.E. Ciotti, M. Dosaka-Akita, H. Fukayama, M. Goto, A. Spandidos, D.A. Gorgoulis, V. Heideman, D.A.M. van Boerdonk, R.A.A. Hiroshima, K. Iwakawa, R. Kastrinakis, N.G. Kinoshita, I. Akiba, S. Landi, M.T. Liu, H. Wang, J.-L. Mehra, R. Khuri, F.R. Lim, W.-T. Owonikoko, T.K. Ramalingam, S. Sarchianaki, E. Syrjanen, K. Tsao, M.-S. Sykes, J. Hee, S.W. Yokota, J. Zaravinos, A. Taioli, E. and Ragin, C. Obikoya-Malomo, M. Kim, S. Chen, Z. Flores-Obando, R. Gibbs, D. Koriyama, C. Aguayo, F. Koshiol, J. Caporaso, N.E. Carpagnano, G.E. Ciotti, M. Dosaka-Akita, H. Fukayama, M. Goto, A. Spandidos, D.A. Gorgoulis, V. Heideman, D.A.M. van Boerdonk, R.A.A. Hiroshima, K. Iwakawa, R. Kastrinakis, N.G. Kinoshita, I. Akiba, S. Landi, M.T. Liu, H. Wang, J.-L. Mehra, R. Khuri, F.R. Lim, W.-T. Owonikoko, T.K. Ramalingam, S. Sarchianaki, E. Syrjanen, K. Tsao, M.-S. Sykes, J. Hee, S.W. Yokota, J. Zaravinos, A. Taioli, E.

Abstract

Human papillomavirus (HPV) is the etiologic risk factor for cervical cancer. Some studies have suggested an association with a subset of lung tumors, but the etiologic link has not been firmly established. We performed an international pooled analysis of crosssectional studies (27 datasets, n = 3249 patients) to evaluate HPV DNA prevalence in lung cancer and to investigate viral presence according to clinical and demographic characteristics. HPV16/18 were the most commonly detected, but with substantial variation in viral prevalence between geographic regions. The highest prevalence of HPV16/18 was observed in South and Central America, followed by Asia, North America and Europe (adjusted prevalence rates = 22, 5, 4 and 3%, respectively). Higher HPV16 prevalence was noted in each geographic region compared with HPV18, except in North America. HPV16/18-positive lung cancer was less likely observed among White race (adjusted odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.12-0.90), whereas no associations were observed with gender, smoking history, age, histology or stage. Comparisons between tumor and normal lung tissue show that HPV was more likely to be present in lung cancer rather than normal lung tissues (OR = 3.86, 95% CI = 2.87-5.19). Among a subset of patients with HPV16-positive tumors, integration was primarily among female patients (93%, 13/14), while the physical status in male cases (N = 14) was inconsistent. Our findings confirm that HPV DNA is present in a small fraction of lung tumors, with large geographic variations. Further comprehensive analysis is needed to assess whether this association reflects a causal relationship. © The Author 2014. Published by Oxford University Press. All rights reserved.

Published
2014

7. Camptothecin resistance:role of the ATP-binding cassette (ABC), mitoxantrone-resistance half-transporter (MXR), and potential for glucuronidation in MXR-expressing cells

Author

Brangi, M, Litman, Thomas, Ciotti, M, Nishiyama, K, Kohlhagen, G, Takimoto, C, Robey, R, Pommier, Y, Fojo, T, Bates, S E, Brangi, M, Litman, Thomas, Ciotti, M, Nishiyama, K, Kohlhagen, G, Takimoto, C, Robey, R, Pommier, Y, Fojo, T, and Bates, S E

Abstract

The mitoxantrone resistance (MXR) gene encodes a recently characterized ATP-binding cassette half-transporter that confers multidrug resistance. We studied resistance to the camptothecins in two sublines expressing high levels of MXR: S1-M1-80 cells derived from parental S1 colon cancer cells and MCF-7 AdVp3,000 isolated from parental MCF-7 breast cancer cells. Both cell lines were 400- to 1,000-fold more resistant to topotecan, 9-amino-20(S)-camptothecin, and the active metabolite of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), than their parental cell lines. The cell lines demonstrated much less resistance to camptothecin and to several camptothecin analogues. Reduced accumulation and energy-dependent efflux of topotecan was demonstrated by confocal microscopy. A significant reduction in cleavable complexes in the resistant cells could be observed after SN-38 treatment but not after camptothecin treatment. In addition to topotecan and SN-38, MXR-overexpressing cells are highly resistant to mitoxantrone and epirubicin. Because these compounds are susceptible to glucuronidation, we examined UDP-glucurono-syltransferase (UGT) activity in parental and resistant cells by TLC. Glucuronides were found at equal levels in both parental and resistant colon cancer cell lines for epirubicin and to a lesser extent for SN-38 and mitoxantrone. Low levels of glucuronidation could also be detected in the resistant breast cancer cells. These results were confirmed by analysis of the UGT1A family mRNAs. We thus conclude that colon and breast cancer cells have a capacity for glucuronidation that could contribute to intrinsic drug resistance in colon cancer cells and may be acquired in breast cancer cells. The lack of selection for higher levels of UGT capacity in the colon cells suggests that high levels of expression of MXR alone are sufficient to confer resistance to the camptothecins.

Published
1999

8. Camptothecin resistance:role of the ATP-binding cassette (ABC), mitoxantrone-resistance half-transporter (MXR), and potential for glucuronidation in MXR-expressing cells

Author

Brangi, M, Litman, Thomas, Ciotti, M, Nishiyama, K, Kohlhagen, G, Takimoto, C, Robey, R, Pommier, Y, Fojo, T, Bates, S E, Brangi, M, Litman, Thomas, Ciotti, M, Nishiyama, K, Kohlhagen, G, Takimoto, C, Robey, R, Pommier, Y, Fojo, T, and Bates, S E

Abstract

The mitoxantrone resistance (MXR) gene encodes a recently characterized ATP-binding cassette half-transporter that confers multidrug resistance. We studied resistance to the camptothecins in two sublines expressing high levels of MXR: S1-M1-80 cells derived from parental S1 colon cancer cells and MCF-7 AdVp3,000 isolated from parental MCF-7 breast cancer cells. Both cell lines were 400- to 1,000-fold more resistant to topotecan, 9-amino-20(S)-camptothecin, and the active metabolite of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), than their parental cell lines. The cell lines demonstrated much less resistance to camptothecin and to several camptothecin analogues. Reduced accumulation and energy-dependent efflux of topotecan was demonstrated by confocal microscopy. A significant reduction in cleavable complexes in the resistant cells could be observed after SN-38 treatment but not after camptothecin treatment. In addition to topotecan and SN-38, MXR-overexpressing cells are highly resistant to mitoxantrone and epirubicin. Because these compounds are susceptible to glucuronidation, we examined UDP-glucurono-syltransferase (UGT) activity in parental and resistant cells by TLC. Glucuronides were found at equal levels in both parental and resistant colon cancer cell lines for epirubicin and to a lesser extent for SN-38 and mitoxantrone. Low levels of glucuronidation could also be detected in the resistant breast cancer cells. These results were confirmed by analysis of the UGT1A family mRNAs. We thus conclude that colon and breast cancer cells have a capacity for glucuronidation that could contribute to intrinsic drug resistance in colon cancer cells and may be acquired in breast cancer cells. The lack of selection for higher levels of UGT capacity in the colon cells suggests that high levels of expression of MXR alone are sufficient to confer resistance to the camptothecins.

Published
1999

9. Camptothecin resistance:role of the ATP-binding cassette (ABC), mitoxantrone-resistance half-transporter (MXR), and potential for glucuronidation in MXR-expressing cells

Author

Brangi, M, Litman, Thomas, Ciotti, M, Nishiyama, K, Kohlhagen, G, Takimoto, C, Robey, R, Pommier, Y, Fojo, T, Bates, S E, Brangi, M, Litman, Thomas, Ciotti, M, Nishiyama, K, Kohlhagen, G, Takimoto, C, Robey, R, Pommier, Y, Fojo, T, and Bates, S E

Abstract

The mitoxantrone resistance (MXR) gene encodes a recently characterized ATP-binding cassette half-transporter that confers multidrug resistance. We studied resistance to the camptothecins in two sublines expressing high levels of MXR: S1-M1-80 cells derived from parental S1 colon cancer cells and MCF-7 AdVp3,000 isolated from parental MCF-7 breast cancer cells. Both cell lines were 400- to 1,000-fold more resistant to topotecan, 9-amino-20(S)-camptothecin, and the active metabolite of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), than their parental cell lines. The cell lines demonstrated much less resistance to camptothecin and to several camptothecin analogues. Reduced accumulation and energy-dependent efflux of topotecan was demonstrated by confocal microscopy. A significant reduction in cleavable complexes in the resistant cells could be observed after SN-38 treatment but not after camptothecin treatment. In addition to topotecan and SN-38, MXR-overexpressing cells are highly resistant to mitoxantrone and epirubicin. Because these compounds are susceptible to glucuronidation, we examined UDP-glucurono-syltransferase (UGT) activity in parental and resistant cells by TLC. Glucuronides were found at equal levels in both parental and resistant colon cancer cell lines for epirubicin and to a lesser extent for SN-38 and mitoxantrone. Low levels of glucuronidation could also be detected in the resistant breast cancer cells. These results were confirmed by analysis of the UGT1A family mRNAs. We thus conclude that colon and breast cancer cells have a capacity for glucuronidation that could contribute to intrinsic drug resistance in colon cancer cells and may be acquired in breast cancer cells. The lack of selection for higher levels of UGT capacity in the colon cells suggests that high levels of expression of MXR alone are sufficient to confer resistance to the camptothecins.

Published
1999

Catalog

Books, media, physical & digital resources
See catalog results