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115 results on '"Pesenti Gritti A"'

1. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial

Author

Accurso, Antonello, Agostara, Biagio, Aieta, Michele, Alabiso, Oscar, Alicicco, Maria Grazia, Amadori, Dino, Amaducci, Laura, Amiconi, Gianna, Antuzzi, Giustino, Ardine, Mara, Ardizzoia, Antonio, Aversa, Caterina, Badalamenti, Giuseppe, Barni, Sandro, Basurto, Carlo, Berardi, Rossana, Bergamasco, Cinzia, Bidoli, Paolo, Bighin, Claudia, Biondi, Edoardo, Bisagni, Giancarlo, Boni, Corrado, Borgonovo, Karen, Botta, Mario, Bravi, Stefano, Bruzzi, Paolo, Buono, Giuseppe, Butera, Alfredo, Caldara, Alessia, Candeloro, Giampiero, Cappelletti, Claudia, Cardalesi, Cinzia, Carfora, Elisabetta, Cariello, Anna, Carrozza, Francesco, Cartenì, Giacomo, Caruso, Michele, Casadei, Virginia, Casanova, Claudia, Castori, Luigi, Cavanna, Luigi, Cavazzini, Giovanna, Cazzaniga, Marina, Chilelli, Mario, Chiodini, Paolo, Chiorrini, Silvia, Ciardiello, Fortunato, Ciccarese, Mariangela, Cinieri, Saverio, Clerico, Mario, Coccaro, Mariarosa, Comande, Mario, Corbo, Claudia, Cortino, Giuseppina, Cusenza, Stefania, Daniele, Gennaro, D'arco, Alfonso Maria, D'auria, Giuliana, Dazzi, Claudio, De Angelis, Carmine, de Braud, Filippo, De Feo, Gianfranco, De Matteis, Andrea, De Tursi, Michele, Di Blasio, Anna, di Lucca, Giuseppe, Di Lullo, Liberato, Di Rella, Francesca, Di Renzo, Gianfranco, Di Stefano, Pia, Di Stefano, Aida, Diana, Anna, Donati, Sara, Fabbri, Agnese, Fabi, Alessandra, Faedi, Marina, Farina, Gabriella, Farris, Antonio, Febbraro, Antonio, Fedele, Palma, Federico, Piera, Ferraù, Francesco, Ferretti, Gianluigi, Ferro, Antonella, Floriani, Irene, Forcignanò, Rosachiara, Forciniti, Samantha, Forestieri, Valeria, Fornari, Gianni, Frisinghelli, Michela, Fusco, Vittorio, Gallizzi, Giulia, Galvano, Antonio, Gambardella, Antonio, Gambi, Angelo, Gebbia, Vittorio, Gervasi, Erika, Ghilardi, Mara, Giacobino, Alice, Giardina, Giovanni, Giotta, Francesco, Giraudi, Sara, Giuliano, Mario, Grassadonia, Antonino, Grasso, Donatella, Grosso, Federica, Guizzaro, Lorenzo, Incoronato, Pasquale, Incorvaia, Lorena, Iodice, Giovanni, La Verde, Nicla, Labonia, Vincenzo, Landi, Gabriella, Latorre, Agnese, Leonardi, Vita, Levaggi, Alessia, Limite, Gennaro, Lina Bascialla, Linda, Livi, Lorenzo, Maiello, Evaristo, Mandelli, Daniela, Marcon, Ilaria, Menon, Daniela, Montedoro, Michele, Moraca, Lucia, Moretti, Anna, Morritti, Maria Grazia, Morselli, Patrizia, Mura, Antonella, Mura, Silvia, Musacchio, Michela, Muzio, Alberto, Natale, Donato, Natoli, Clara, Nigro, Cinzia, Nisticò, Cecilia, Nuzzo, Antonio, Orditura, Michele, Orlando, Laura, Pacilio, Carmen, Palumbo, Giuliano, Palumbo, Raffaella, Pasini, Felice, Paterno, Emanuela, Pazzola, Antonio, Pelliccioni, Silvia, Pensabene, Matilde, Perroni, Davide, Pesenti Gritti, Angela, Petrelli, Fausto, Piccirillo, Maria Carmela, Pinotti, Graziella, Pogliani, Claudia, Poli, Davide, Prader, Sonia, Recchia, Francesco, Rizzi, Daniele, Romano, Carmen, Rossello, Rosalba, Rossini, Chiara, Salvucci, Giuseppina, Sanna, Valeria, Santini, Alessandra, Saracchini, Silvana, Savastano, Clementina, Scambia, Giovanni, Schettini, Francesco, Schiavone, Paola, Schirone, Alessio, Seles, Elena, Signoriello, Simona, Signoriello, Giuseppe, Silva, Rosa Rita, Silvestri, Antonia, Simeon, Vittorio, Spagnoletti, Ilaria, Tamberi, Stefano, Teragni, Cristina, Thalmann, Verena, Thomas, Renato, Thomas, Guglielmo, Tienghi, Amelia, Tinari, Nicola, Tinessa, Vincenza, Tomei, Federica, Tonini, Giuseppe, Torri, Valter, Traficante, Divina, Tudini, Marianna, Turazza, Monica, Vignoli, Roberto, Vitale, Maria Giuseppa, Zacchia, Alessandra, Zagarese, Pasquale, Zanni, Alda, Zavallone, Laura, Zavettieri, Maria, Zoboli, Alessandra, De Placido, Sabino, Gallo, Ciro, De Laurentiis, Michelino, Arpino, Grazia, Sarobba, Maria Giuseppa, Riccardi, Ferdinando, Russo, Antonio, Del Mastro, Lucia, Cogoni, Alessio Aligi, Cognetti, Francesco, Gori, Stefania, Foglietta, Jennifer, Frassoldati, Antonio, Amoroso, Domenico, Laudadio, Lucio, Moscetti, Luca, Montemurro, Filippo, Verusio, Claudio, Bernardo, Antonio, Lorusso, Vito, Gravina, Adriano, Moretti, Gabriella, Lauria, Rossella, Lai, Antonella, Mocerino, Carmela, Rizzo, Sergio, Nuzzo, Francesco, Carlini, Paolo, and Perrone, Francesco

Published
2018
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2. Multicenter, randomised, open-label, non-comparative phase 2 trial on the efficacy and safety of the combination of bevacizumab and trabectedin with or without carboplatin in women with partially platinum-sensitive recurrent ovarian cancer

Author

Colombo, Nicoletta, Zaccarelli, Eleonora, Baldoni, Alessandra, Frezzini, Simona, Scambia, Giovanni, Palluzzi, Eleonora, Tognon, Germana, Lissoni, Andrea A., Rubino, Daniela, Ferrero, Annamaria, Farina, Gabriella, Negri, Emanuele, Pesenti Gritti, Angela, Galli, Francesca, Biagioli, Elena, Rulli, Eliana, Poli, Davide, Gerardi, Chiara, Torri, Valter, Fossati, Roldano, and D‘Incalci, Maurizio

Published
2019
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9. A General Population Twin Study of the CBCL/6-18 DSM-Oriented Scales

Author

Spatola, Chiara A. M., Fagnani, Corrado, Pesenti-Gritti, Paola, Ogliari, Anna, Stazi, Maria-Antonietta, and Battaglia, Marco

Abstract

Objective: To explore the contributions of genetic and environmental influences to individual variation and covariation of the Child Behavior Checklist (CBCL) DSM-oriented scales (DOS) originally proposed by Achenbach and associates in 2001. Method: A classic twin study of 398 twin pairs ages 8 to 17 years belonging to the population-based Italian Twin Registry, assessed by parents using the CBCL for Ages 6 to 18 (CBCL/6-18). Results: Univariate analyses showed that compared with the classic CBCL/6-18 empirical subscales, the DOS have higher heritability (lowest 0.54 for Anxiety Problems, highest 0.71 for Conduct Problems) and simpler causal structure in that the phenotypic variance was satisfactorily explained by additive genetic and unique environmental factors only. Multivariate analyses showed that the causes of phenotypic correlation among the different DOS can be attributed to one common genetic factor and to two idiosyncratic environmental factors, each loading differently on the Internalizing (Anxiety and Affective Problems) and the Externalizing(Attention-Deficit/Hyperactivity, Oppositional Defiant, and Conduct Problems) CBCL/6-18 DOS. Conclusions: Several common risk factors of both genetic and environmental nature can simultaneously affect a child's proneness to develop the psychopathological signs and symptoms captured by the CBCL/6-18 DOS. (Contains 4 tables and 1 figure.)

Published
2007

14. Multicenter, randomised, open-label, non-comparative phase 2 trial on the efficacy and safety of the combination of bevacizumab and trabectedin with or without carboplatin in women with partially platinum-sensitive recurrent ovarian cancer

Author

Colombo, N, Zaccarelli, E, Baldoni, A, Frezzini, S, Scambia, G, Palluzzi, E, Tognon, G, Lissoni, A, Rubino, D, Ferrero, A, Farina, G, Negri, E, Pesenti Gritti, A, Galli, F, Biagioli, E, Rulli, E, Poli, D, Gerardi, C, Torri, V, Fossati, R, D'Incalci, M, Colombo, Nicoletta, Zaccarelli, Eleonora, Baldoni, Alessandra, Frezzini, Simona, Scambia, Giovanni, Palluzzi, Eleonora, Tognon, Germana, Lissoni, Andrea A, Rubino, Daniela, Ferrero, Annamaria, Farina, Gabriella, Negri, Emanuele, Pesenti Gritti, Angela, Galli, Francesca, Biagioli, Elena, Rulli, Eliana, Poli, Davide, Gerardi, Chiara, Torri, Valter, Fossati, Roldano, D'Incalci, Maurizio, Colombo, N, Zaccarelli, E, Baldoni, A, Frezzini, S, Scambia, G, Palluzzi, E, Tognon, G, Lissoni, A, Rubino, D, Ferrero, A, Farina, G, Negri, E, Pesenti Gritti, A, Galli, F, Biagioli, E, Rulli, E, Poli, D, Gerardi, C, Torri, V, Fossati, R, D'Incalci, M, Colombo, Nicoletta, Zaccarelli, Eleonora, Baldoni, Alessandra, Frezzini, Simona, Scambia, Giovanni, Palluzzi, Eleonora, Tognon, Germana, Lissoni, Andrea A, Rubino, Daniela, Ferrero, Annamaria, Farina, Gabriella, Negri, Emanuele, Pesenti Gritti, Angela, Galli, Francesca, Biagioli, Elena, Rulli, Eliana, Poli, Davide, Gerardi, Chiara, Torri, Valter, Fossati, Roldano, and D'Incalci, Maurizio

Abstract

Background: Trabectedin, in addition to its antiproliferative effect, can modify the tumour microenvironment and this could be synergistic with bevacizumab. The efficacy and safety of trabectedin and bevacizumab ± carboplatin have never been investigated. Methods: In this phase 2 study, women progressing between 6 and 12 months since their last platinum-based therapy were randomised to Arm BT: bevacizumab, trabectedin every 21 days, or Arm BT+C: bevacizumab, trabectedin and carboplatin every 28 days, from cycles 1 to 6, then trabectedin and bevacizumab as in Arm BT. Primary endpoints were progression-free survival rate (PFS-6) and severe toxicity rate (ST-6) at 6 months, assuming a PFS-6 ≤35% for BT and ≤40% for BT+C as not of therapeutic interest and, for both arms, a ST-6 ≥ 30% as unacceptable. Results: BT+C (21 patients) did not meet the safety criteria for the second stage (ST-6 45%; 95%CI: 23%–69%) but PFS-6 was 85% (95%CI: 62%–97%). BT (50 patients) had 75% PFS-6 (95%CI: 60%–87%) and 16% ST-6 (95%CI 7%–30%). Conclusions: BT compared favourably with other platinum- and non-platinum-based regimens. The combination with carboplatin needs to be assessed further in a re-modulated safer schedule to confirm its apparent strong activity. Clinical Trial Registration: NCT01735071 (Clinicaltrials.gov)

Published
2019

15. A genetically informed study of the association between childhood separation anxiety, sensitivity to CO(sub 2), panic disorder, and the effect of childhood parental loss

Author

Battaglia, Marco, Pesenti-Gritti, Paola, Medland, Sarah E., Ogliari, Anna, Tambs, Kristian, and Spatola, Chiara A.M.

Subjects
Separation anxiety (Child psychology) -- Genetic aspects, Separation anxiety (Child psychology) -- Research, Anxiety in children -- Genetic aspects, Anxiety in children -- Research, Panic attacks -- Genetic aspects, Panic attacks -- Research, Panic disorders -- Genetic aspects, Panic disorders -- Research, Carbon dioxide -- Health aspects, Allergic reaction -- Genetic aspects, Allergy -- Genetic aspects, Health, Psychology and mental health
Published
2009

17. Human iPSC-based neurodevelopmental models of globoid cell leukodystrophy uncover patient- and cell type-specific disease phenotypes

Author

Angela Bachi, Elisabeth Mangiameli, Vittoria Matafora, Angela Pesenti Gritti, Lucrezia della Volpe, Lucia Susani, Daniela Gnani, Marianna Paulis, Francesca Sanvito, Sabata Martino, Anna Cecchele, Raffaella Di Micco, Francesco Morena, and Angela Cattaneo

Subjects
0301 basic medicine, Senescence, leukodystrophy, senescence, Genetic enhancement, lysosomal enzymes, Induced Pluripotent Stem Cells, oligodendrocytes, neurons, neural progenitors, Biology, Biochemistry, Article, 03 medical and health sciences, 0302 clinical medicine, Pluripotent stem cells, Genetics, Lysosomal storage disease, medicine, Humans, Genetic Predisposition to Disease, Progenitor cell, Induced pluripotent stem cell, Cells, Cultured, Stem Cells, Neurodegeneration, Leukodystrophy, Psychosine, Cell Differentiation, Cell Biology, Genetic Therapy, medicine.disease, Phenotype, gene therapy, Cell biology, Leukodystrophy, Globoid Cell, Oligodendroglia, 030104 developmental biology, GALC activity, Krabbe disease, 030217 neurology & neurosurgery, Developmental Biology, Galactosylceramidase
Abstract

Summary Globoid cell leukodystrophy (GLD) is a rare neurodegenerative lysosomal storage disease caused by an inherited deficiency of β-galactocerebrosidase (GALC). GLD pathogenesis and therapeutic correction have been poorly studied in patient neural cells. Here, we investigated the impact of GALC deficiency and lentiviral vector-mediated GALC rescue/overexpression in induced pluripotent stem cell (iPSC)-derived neural progenitors and neuronal/glial progeny obtained from two GLD patients. GLD neural progeny displayed progressive psychosine storage, oligodendroglial and neuronal defects, unbalanced lipid composition, and early activation of cellular senescence, depending on the disease-causing mutation. The partial rescue of the neural differentiation program upon GALC reconstitution and psychosine clearance suggests multiple mechanisms contributing to neural pathology in GLD. Also, the pathological phenotype associated to supraphysiological GALC levels highlights the need of regulated GALC expression for proper human neural commitment/differentiation. These data have important implications for establishing safe therapeutic strategies to enhance disease correction of GLD., Highlights • GLD hiPSC-derived neural progenitors show defective neuronal/glial differentiation • GLD neural progeny displays psychosine storage and modest lysosomal impairment • Lipidome unbalance and cellular senescence contribute to the GLD phenotype • Restoring GALC activity partially rescues the GLD phenotypic defects, In this article, Mangiameli et al. study the impact of GALC deficiency and lentiviral vector-mediated GALC rescue/overexpression in GLD hiPSC-derived neural progenitors and their neuronal/glial progeny. The study uncovers unforeseen mutation- and cell type-specific early pathogenic events (i.e. lipid unbalance and activation of a senescence program) that may contribute to GLD neuropathology along with psychosine storage, with important therapeutic implications.

Published
2020

20. Unstable maternal environment, separation anxiety, and heightened CO2 sensitivity induced by gene-by-environment interplay.

Author

Francesca R D'Amato, Claudio Zanettini, Valentina Lampis, Roberto Coccurello, Tiziana Pascucci, Rossella Ventura, Stefano Puglisi-Allegra, Chiara A M Spatola, Paola Pesenti-Gritti, Diego Oddi, Anna Moles, and Marco Battaglia

Subjects
Medicine, Science
Abstract

In man, many different events implying childhood separation from caregivers/unstable parental environment are associated with heightened risk for panic disorder in adulthood. Twin data show that the occurrence of such events in childhood contributes to explaining the covariation between separation anxiety disorder, panic, and the related psychobiological trait of CO(2) hypersensitivity. We hypothesized that early interference with infant-mother interaction could moderate the interspecific trait of response to CO(2) through genetic control of sensitivity to the environment.Having spent the first 24 hours after birth with their biological mother, outbred NMRI mice were cross-fostered to adoptive mothers for the following 4 post-natal days. They were successively compared to normally-reared individuals for: number of ultrasonic vocalizations during isolation, respiratory physiology responses to normal air (20%O(2)), CO(2)-enriched air (6% CO(2)), hypoxic air (10%O(2)), and avoidance of CO(2)-enriched environments.Cross-fostered pups showed significantly more ultrasonic vocalizations, more pronounced hyperventilatory responses (larger tidal volume and minute volume increments) to CO(2)-enriched air and heightened aversion towards CO(2)-enriched environments, than normally-reared individuals. Enhanced tidal volume increment response to 6%CO(2) was present at 16-20, and 75-90 postnatal days, implying the trait's stability. Quantitative genetic analyses of unrelated individuals, sibs and half-sibs, showed that the genetic variance for tidal volume increment during 6%CO(2) breathing was significantly higher (Bartlett χ = 8.3, p = 0.004) among the cross-fostered than the normally-reared individuals, yielding heritability of 0.37 and 0.21 respectively. These results support a stress-diathesis model whereby the genetic influences underlying the response to 6%CO(2) increase their contribution in the presence of an environmental adversity. Maternal grooming/licking behaviour, and corticosterone basal levels were similar among cross-fostered and normally-reared individuals.A mechanism of gene-by-environment interplay connects this form of early perturbation of infant-mother interaction, heightened CO(2) sensitivity and anxiety. Some non-inferential physiological measurements can enhance animal models of human neurodevelopmental anxiety disorders.

Published
2011
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21. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial

Author

Sabino De Placido, Ciro Gallo, Michelino De Laurentiis, Giancarlo Bisagni, Grazia Arpino, Maria Giuseppa Sarobba, Ferdinando Riccardi, Antonio Russo, Lucia Del Mastro, Alessio Aligi Cogoni, Francesco Cognetti, Stefania Gori, Jennifer Foglietta, Antonio Frassoldati, Domenico Amoroso, Lucio Laudadio, Luca Moscetti, Filippo Montemurro, Claudio Verusio, Antonio Bernardo, Vito Lorusso, Adriano Gravina, Gabriella Moretti, Rossella Lauria, Antonella Lai, Carmela Mocerino, Sergio Rizzo, Francesco Nuzzo, Paolo Carlini, Francesco Perrone, Antonello Accurso, Biagio Agostara, Michele Aieta, Oscar Alabiso, Maria Grazia Alicicco, Dino Amadori, Laura Amaducci, Gianna Amiconi, Giustino Antuzzi, Mara Ardine, Antonio Ardizzoia, Caterina Aversa, Giuseppe Badalamenti, Sandro Barni, Carlo Basurto, Rossana Berardi, Cinzia Bergamasco, Paolo Bidoli, Claudia Bighin, Edoardo Biondi, Corrado Boni, Karen Borgonovo, Mario Botta, Stefano Bravi, Paolo Bruzzi, Giuseppe Buono, Alfredo Butera, Alessia Caldara, Giampiero Candeloro, Claudia Cappelletti, Cinzia Cardalesi, Elisabetta Carfora, Anna Cariello, Francesco Carrozza, Giacomo Cartenì, Michele Caruso, Virginia Casadei, Claudia Casanova, Luigi Castori, Luigi Cavanna, Giovanna Cavazzini, Marina Cazzaniga, Mario Chilelli, Paolo Chiodini, Silvia Chiorrini, Fortunato Ciardiello, Mariangela Ciccarese, Saverio Cinieri, Mario Clerico, Mariarosa Coccaro, Mario Comande, Claudia Corbo, Giuseppina Cortino, Stefania Cusenza, Gennaro Daniele, Alfonso Maria D'arco, Giuliana D'auria, Claudio Dazzi, Carmine De Angelis, Filippo de Braud, Gianfranco De Feo, Andrea De Matteis, Michele De Tursi, Anna Di Blasio, Giuseppe di Lucca, Liberato Di Lullo, Francesca Di Rella, Gianfranco Di Renzo, Pia Di Stefano, Aida Di Stefano, Anna Diana, Sara Donati, Agnese Fabbri, Alessandra Fabi, Marina Faedi, Gabriella Farina, Antonio Farris, Antonio Febbraro, Palma Fedele, Piera Federico, Francesco Ferraù, Gianluigi Ferretti, Antonella Ferro, Irene Floriani, Rosachiara Forcignanò, Samantha Forciniti, Valeria Forestieri, Gianni Fornari, Michela Frisinghelli, Vittorio Fusco, Giulia Gallizzi, Antonio Galvano, Antonio Gambardella, Angelo Gambi, Vittorio Gebbia, Erika Gervasi, Mara Ghilardi, Alice Giacobino, Giovanni Giardina, Francesco Giotta, Sara Giraudi, Mario Giuliano, Antonino Grassadonia, Donatella Grasso, Federica Grosso, Lorenzo Guizzaro, Pasquale Incoronato, Lorena Incorvaia, Giovanni Iodice, Nicla La Verde, Vincenzo Labonia, Gabriella Landi, Agnese Latorre, Vita Leonardi, Alessia Levaggi, Gennaro Limite, Linda Lina Bascialla, Lorenzo Livi, Evaristo Maiello, Daniela Mandelli, Ilaria Marcon, Daniela Menon, Michele Montedoro, Lucia Moraca, Anna Moretti, Maria Grazia Morritti, Patrizia Morselli, Antonella Mura, Silvia Mura, Michela Musacchio, Alberto Muzio, Donato Natale, Clara Natoli, Cinzia Nigro, Cecilia Nisticò, Antonio Nuzzo, Michele Orditura, Laura Orlando, Carmen Pacilio, Giuliano Palumbo, Raffaella Palumbo, Felice Pasini, Emanuela Paterno, Antonio Pazzola, Silvia Pelliccioni, Matilde Pensabene, Davide Perroni, Angela Pesenti Gritti, Fausto Petrelli, Maria Carmela Piccirillo, Graziella Pinotti, Claudia Pogliani, Davide Poli, Sonia Prader, Francesco Recchia, Daniele Rizzi, Carmen Romano, Rosalba Rossello, Chiara Rossini, Giuseppina Salvucci, Valeria Sanna, Alessandra Santini, Silvana Saracchini, Clementina Savastano, Giovanni Scambia, Francesco Schettini, Paola Schiavone, Alessio Schirone, Elena Seles, Simona Signoriello, Giuseppe Signoriello, Rosa Rita Silva, Antonia Silvestri, Vittorio Simeon, Ilaria Spagnoletti, Stefano Tamberi, Cristina Teragni, Verena Thalmann, Renato Thomas, Guglielmo Thomas, Amelia Tienghi, Nicola Tinari, Vincenza Tinessa, Federica Tomei, Giuseppe Tonini, Valter Torri, Divina Traficante, Marianna Tudini, Monica Turazza, Roberto Vignoli, Maria Giuseppa Vitale, Alessandra Zacchia, Pasquale Zagarese, Alda Zanni, Laura Zavallone, Maria Zavettieri, Alessandra Zoboli, De Placido, S., Gallo, C., De Laurentiis, M., Bisagni, G., Arpino, G., Sarobba, M. G., Riccardi, F., Russo, A., Del Mastro, L., Cogoni, A. A., Cognetti, F., Gori, S., Foglietta, J., Frassoldati, A., Amoroso, D., Laudadio, L., Moscetti, L., Montemurro, F., Verusio, C., Bernardo, A., Lorusso, V., Gravina, A., Moretti, G., Lauria, R., Lai, A., Mocerino, C., Rizzo, S., Nuzzo, F., Carlini, P., Perrone, F., Accurso, A., Agostara, B., Aieta, M., Alabiso, O., Alicicco, M. G., Amadori, D., Amaducci, L., Amiconi, G., Antuzzi, G., Ardine, M., Ardizzoia, A., Aversa, C., Badalamenti, G., Barni, S., Basurto, C., Berardi, R., Bergamasco, C., Bidoli, P., Bighin, C., Biondi, E., Boni, C., Borgonovo, K., Botta, M., Bravi, S., Bruzzi, P., Buono, G., Butera, A., Caldara, A., Candeloro, G., Cappelletti, C., Cardalesi, C., Carfora, E., Cariello, A., Carrozza, F., Carteni, G., Caruso, M., Casadei, V., Casanova, C., Castori, L., Cavanna, L., Cavazzini, G., Cazzaniga, M., Chilelli, M., Chiodini, P., Chiorrini, S., Ciardiello, F., Ciccarese, M., Cinieri, S., Clerico, M., Coccaro, M., Comande, M., Corbo, C., Cortino, G., Cusenza, S., Daniele, G., D'Arco, A. M., D'Auria, G., Dazzi, C., De Angelis, C., de Braud, F., De Feo, G., De Matteis, Ma., De Tursi, M., Di Blasio, A., di Lucca, G., Di Lullo, L., Di Rella, F., Di Renzo, G., Di Stefano, P., Di Stefano, A., Diana, A., Donati, S., Fabbri, A., Fabi, A., Faedi, M., Farina, G., Farris, A., Febbraro, A., Fedele, P., Federico, P., Ferrau, F., Ferretti, G., Ferro, A., Floriani, I., Forcignano, R., Forciniti, S., Forestieri, V., Fornari, G., Frisinghelli, M., Fusco, V., Gallizzi, G., Galvano, A., Gambardella, A., Gambi, A., Gebbia, V., Gervasi, E., Ghilardi, M., Giacobino, A., Giardina, G., Giotta, F., Giraudi, S., Giuliano, M., Grassadonia, A., Grasso, D., Grosso, F., Guizzaro, L., Incoronato, P., Incorvaia, L., Iodice, G., La Verde, N., Labonia, V., Landi, G., Latorre, A., Leonardi, V., Levaggi, A., Limite, G., Lina Bascialla, L., Livi, L., Maiello, E., Mandelli, D., Marcon, I., Menon, D., Montedoro, M., Moraca, L., Moretti, A., Morritti, M. G., Morselli, P., Mura, A., Mura, S., Musacchio, M., Muzio, A., Natale, D., Natoli, C., Nigro, C., Nistico, C., Nuzzo, A., Orditura, M., Orlando, L., Pacilio, C., Palumbo, G., Palumbo, R., Pasini, F., Paterno, E., Pazzola, A., Pelliccioni, S., Pensabene, M., Perroni, D., Pesenti Gritti, A., Petrelli, F., Piccirillo, M. C., Pinotti, G., Pogliani, C., Poli, D., Prader, S., Recchia, F., Rizzi, D., Romano, C., Rossello, R., Rossini, C., Salvucci, G., Sanna, V., Santini, A., Saracchini, S., Savastano, C., Scambia, G., Schettini, F., Schiavone, P., Schirone, A., Seles, E., Signoriello, S., Signoriello, G., Silva, R. R., Silvestri, A., Simeon, V., Spagnoletti, I., Tamberi, S., Teragni, C., Thalmann, V., Thomas, R., Thomas, G., Tienghi, A., Tinari, N., Tinessa, V., Tomei, F., Tonini, G., Torri, V., Traficante, D., Tudini, M., Turazza, M., Vignoli, R., Vitale, M. G., Zacchia, A., Zagarese, P., Zanni, A., Zavallone, L., Zavettieri, M., Zoboli, A., De Placido, Sabino, Gallo, Ciro, De Laurentiis, Michelino, Bisagni, Giancarlo, Arpino, Grazia, Sarobba, Maria Giuseppa, Riccardi, Ferdinando, Russo, Antonio, Del Mastro, Lucia, Cogoni, Alessio Aligi, Cognetti, Francesco, Gori, Stefania, Foglietta, Jennifer, Frassoldati, Antonio, Amoroso, Domenico, Laudadio, Lucio, Moscetti, Luca, Montemurro, Filippo, Verusio, Claudio, Bernardo, Antonio, Lorusso, Vito, Gravina, Adriano, Moretti, Gabriella, Lauria, Rossella, Lai, Antonella, Mocerino, Carmen, Rizzo, Sergio, Nuzzo, Francesco, Carlini, Paolo, Perrone, Francesco, Accurso, Antonello, Agostara, Biagio, Aieta, Michele, Alabiso, Oscar, Alicicco, Maria Grazia, Amadori, Dino, Amaducci, Laura, Amiconi, Gianna, Antuzzi, Giustino, Ardine, Mara, Ardizzoia, Antonio, Aversa, Caterina, Badalamenti, Giuseppe, Barni, Sandro, Basurto, Carlo, Berardi, Rossana, Bergamasco, Cinzia, Bidoli, Paolo, Bighin, Claudia, Biondi, Edoardo, Boni, Corrado, Borgonovo, Karen, Botta, Mario, Bravi, Stefano, Bruzzi, Paolo, Buono, Giuseppe, Butera, Alfredo, Caldara, Alessia, Candeloro, Giampiero, Cappelletti, Claudia, Cardalesi, Cinzia, Carfora, Elisabetta, Cariello, Anna, Carrozza, Francesco, Cartenì, Giacomo, Caruso, Michele, Casadei, Virginia, Casanova, Claudia, Castori, Luigi, Cavanna, Luigi, Cavazzini, Giovanna, Cazzaniga, Marina, Chilelli, Mario, Chiodini, Paolo, Chiorrini, Silvia, Ciardiello, Fortunato, Ciccarese, Mariangela, Cinieri, Saverio, Clerico, Mario, Coccaro, Mariarosa, Comande, Mario, Corbo, Claudia, Cortino, Giuseppina, Cusenza, Stefania, Daniele, Gennaro, D'arco, Alfonso Maria, D'auria, Giuliana, Dazzi, Claudio, De Angelis, Carmine, de Braud, Filippo, De Feo, Gianfranco, De Matteis, Andrea, De Tursi, Michele, Di Blasio, Anna, di Lucca, Giuseppe, Di Lullo, Liberato, Di Rella, Francesca, Di Renzo, Gianfranco, Di Stefano, Pia, Di Stefano, Aida, Diana, Anna, Donati, Sara, Fabbri, Agnese, Fabi, Alessandra, Faedi, Marina, Farina, Gabriella, Farris, Antonio, Febbraro, Antonio, Fedele, Palma, Federico, Piera, Ferraù, Francesco, Ferretti, Gianluigi, Ferro, Antonella, Floriani, Irene, Forcignanò, Rosachiara, Forciniti, Samantha, Forestieri, Valeria, Fornari, Gianni, Frisinghelli, Michela, Fusco, Vittorio, Gallizzi, Giulia, Galvano, Antonio, Gambardella, Antonio, Gambi, Angelo, Gebbia, Vittorio, Gervasi, Erika, Ghilardi, Mara, Giacobino, Alice, Giardina, Giovanni, Giotta, Francesco, Giraudi, Sara, Giuliano, Mario, Grassadonia, Antonino, Grasso, Donatella, Grosso, Federica, Guizzaro, Lorenzo, Incoronato, Pasquale, Incorvaia, Lorena, Iodice, Giovanni, La Verde, Nicla, Labonia, Vincenzo, Landi, Gabriella, Latorre, Agnese, Leonardi, Vita, Levaggi, Alessia, Limite, Gennaro, Lina Bascialla, Linda, Livi, Lorenzo, Maiello, Evaristo, Mandelli, Daniela, Marcon, Ilaria, Menon, Daniela, Montedoro, Michele, Moraca, Lucia, Moretti, Anna, Morritti, Maria Grazia, Morselli, Patrizia, Mura, Antonella, Mura, Silvia, Musacchio, Michela, Muzio, Alberto, Natale, Donato, Natoli, Clara, Nigro, Cinzia, Nisticò, Cecilia, Nuzzo, Antonio, Orditura, Michele, Orlando, Laura, Pacilio, Carmen, Palumbo, Giuliano, Palumbo, Raffaella, Pasini, Felice, Paterno, Emanuela, Pazzola, Antonio, Pelliccioni, Silvia, Pensabene, Matilde, Perroni, Davide, Pesenti Gritti, Angela, Petrelli, Fausto, Piccirillo, Maria Carmela, Pinotti, Graziella, Pogliani, Claudia, Poli, Davide, Prader, Sonia, Recchia, Francesco, Rizzi, Daniele, Romano, Carmen, Rossello, Rosalba, Rossini, Chiara, Salvucci, Giuseppina, Sanna, Valeria, Santini, Alessandra, Saracchini, Silvana, Savastano, Clementina, Scambia, Giovanni, Schettini, Francesco, Schiavone, Paola, Schirone, Alessio, Seles, Elena, Signoriello, Simona, Signoriello, Giuseppe, Silva, Rosa Rita, Silvestri, Antonia, Simeon, Vittorio, Spagnoletti, Ilaria, Tamberi, Stefano, Teragni, Cristina, Thalmann, Verena, Thomas, Renato, Thomas, Guglielmo, Tienghi, Amelia, Tinari, Nicola, Tinessa, Vincenza, Tomei, Federica, Tonini, Giuseppe, Torri, Valter, Traficante, Divina, Tudini, Marianna, Turazza, Monica, Vignoli, Roberto, Vitale, Maria Giuseppa, Zacchia, Alessandra, Zagarese, Pasquale, Zanni, Alda, Zavallone, Laura, Zavettieri, Maria, Zoboli, Alessandra, Mocerino, Carmela, D'Arco, Alfonso Maria, D'Auria, Giuliana, De Placido, S, Gallo, C, De Laurentiis, M, Bisagni, G, Arpino, G, Sarobba, M, Riccardi, F, Russo, A, Del Mastro, L, Cogoni, A, Cognetti, F, Gori, S, Foglietta, J, Frassoldati, A, Amoroso, D, Laudadio, L, Moscetti, L, Montemurro, F, Verusio, C, Bernardo, A, Lorusso, V, Gravina, A, Moretti, G, Lauria, R, Lai, A, Mocerino, C, Rizzo, S, Nuzzo, F, Carlini, P, Perrone, F, Accurso, A, Agostara, B, Aieta, M, Alabiso, O, Alicicco, M, Amadori, D, Amaducci, L, Amiconi, G, Antuzzi, G, Ardine, M, Ardizzoia, A, Aversa, C, Badalamenti, G, Barni, S, Basurto, C, Berardi, R, Bergamasco, C, Bidoli, P, Bighin, C, Biondi, E, Boni, C, Borgonovo, K, Botta, M, Bravi, S, Bruzzi, P, Buono, G, Butera, A, Caldara, A, Candeloro, G, Cappelletti, C, Cardalesi, C, Carfora, E, Cariello, A, Carrozza, F, Carteni, G, Caruso, M, Casadei, V, Casanova, C, Castori, L, Cavanna, L, Cavazzini, G, Cazzaniga, M, Chilelli, M, Chiodini, P, Chiorrini, S, Ciardiello, F, Ciccarese, M, Cinieri, S, Clerico, M, Coccaro, M, Comande, M, Corbo, C, Cortino, G, Cusenza, S, Daniele, G, D'Arco, A, D'Auria, G, Dazzi, C, De Angelis, C, de Braud, F, De Feo, G, De Matteis, A, De Tursi, M, Di Blasio, A, di Lucca, G, Di Lullo, L, Di Rella, F, Di Renzo, G, Di Stefano, P, Di Stefano, A, Diana, A, Donati, S, Fabbri, A, Fabi, A, Faedi, M, Farina, G, Farris, A, Febbraro, A, Fedele, P, Federico, P, Ferrau, F, Ferretti, G, Ferro, A, Floriani, I, Forcignano, R, Forciniti, S, Forestieri, V, Fornari, G, Frisinghelli, M, Fusco, V, Gallizzi, G, Galvano, A, Gambardella, A, Gambi, A, Gebbia, V, Gervasi, E, Ghilardi, M, Giacobino, A, Giardina, G, Giotta, F, Giraudi, S, Giuliano, M, Grassadonia, A, Grasso, D, Grosso, F, Guizzaro, L, Incoronato, P, Incorvaia, L, Iodice, G, La Verde, N, Labonia, V, Landi, G, Latorre, A, Leonardi, V, Levaggi, A, Limite, G, Lina Bascialla, L, Livi, L, Maiello, E, Mandelli, D, Marcon, I, Menon, D, Montedoro, M, Moraca, L, Moretti, A, Morritti, M, Morselli, P, Mura, A, Mura, S, Musacchio, M, Muzio, A, Natale, D, Natoli, C, Nigro, C, Nistico, C, Nuzzo, A, Orditura, M, Orlando, L, Pacilio, C, Palumbo, G, Palumbo, R, Pasini, F, Paterno, E, Pazzola, A, Pelliccioni, S, Pensabene, M, Perroni, D, Pesenti Gritti, A, Petrelli, F, Piccirillo, M, Pinotti, G, Pogliani, C, Poli, D, Prader, S, Recchia, F, Rizzi, D, Romano, C, Rossello, R, Rossini, C, Salvucci, G, Sanna, V, Santini, A, Saracchini, S, Savastano, C, Scambia, G, Schettini, F, Schiavone, P, Schirone, A, Seles, E, Signoriello, S, Signoriello, G, Silva, R, Silvestri, A, Simeon, V, Spagnoletti, I, Tamberi, S, Teragni, C, Thalmann, V, Thomas, R, Thomas, G, Tienghi, A, Tinari, N, Tinessa, V, Tomei, F, Tonini, G, Torri, V, Traficante, D, Tudini, M, Turazza, M, Vignoli, R, Vitale, M, Zacchia, A, Zagarese, P, Zanni, A, Zavallone, L, Zavettieri, M, and Zoboli, A

Subjects
Oncology, Receptor, ErbB-2, Settore MED/06 - Oncologia Medica, letrozole, law.invention, Adjuvant anastrozole, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, Exemestane, law, exemestane, tamoxifen, breast cancer, Antineoplastic Combined Chemotherapy Protocols, 030212 general & internal medicine, Aromatase Inhibitors, Letrozole, Hazard ratio, Middle Aged, Receptors, Estrogen, Tolerability, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, Receptors, Progesterone, Breast Neoplasm, Human, medicine.drug, medicine.medical_specialty, Socio-culturale, Anastrozole, Breast Neoplasms, Disease-Free Survival, Drug Administration Schedule, 03 medical and health sciences, Breast cancer, Internal medicine, medicine, Aromatase Inhibitor, Humans, Aged, Antineoplastic Combined Chemotherapy Protocol, Androstadiene, business.industry, medicine.disease, Androstadienes, chemistry, business, Tamoxifen
Abstract

Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is registered with the European Clinical Trials Database, number 2006-004018-42, and ClinicalTrials.gov, number NCT00541086. Findings: Between March 9, 2007, and July 31, 2012, 3697 patients were enrolled into the study. After a median follow-up of 60 months (IQR 46–72), 401 disease-free survival events were reported, including 211 (11%) of 1850 patients allocated to the switch strategy and 190 (10%) of 1847 patients allocated to upfront treatment. 5-year disease-free survival was 88·5% (95% CI 86·7–90·0) with the switch strategy and 89·8% (88·2–91·2) with upfront treatment (hazard ratio 0·89, 95% CI 0·73–1·08; p=0·23). 5-year disease-free survival was 90·0% (95% CI 87·9–91·7) with anastrozole (124 events), 88·0% (85·8–89·9) with exemestane (148 events), and 89·4% (87·3 to 91·1) with letrozole (129 events; p=0·24). No unexpected serious adverse reactions or treatment-related deaths occurred. Musculoskeletal side-effects were the most frequent grade 3–4 events, reported in 130 (7%) of 1761 patients who received the switch strategy and 128 (7%) of 1766 patients who received upfront treatment. Grade 1 musculoskeletal events were more frequent with the upfront schedule than with the switch schedule (924 [52%] of 1766 patients vs 745 [42%] of 1761 patients). All other grade 3–4 adverse events occurred in less than 2% of patients in either group. Interpretation: 5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors. None of the three aromatase inhibitors was superior to the others in terms of efficacy. Therefore, patient preference, tolerability, and financial constraints should be considered when deciding the optimal treatment approach in this setting. Funding: Italian Drug Agency.

Published
2018

24. Multicenter, randomised, open-label, non-comparative phase 2 trial on the efficacy and safety of the combination of bevacizumab and trabectedin with or without carboplatin in women with partially platinum-sensitive recurrent ovarian cancer

Author

Simona Frezzini, Eleonora Zaccarelli, Davide Poli, Giovanni Scambia, Roldano Fossati, E. Negri, Valter Torri, Andrea Lissoni, Nicoletta Colombo, Chiara Gerardi, Francesca Galli, Alessandra Baldoni, Germana Tognon, Gabriella Farina, Eleonora Palluzzi, Elena Biagioli, Angela Pesenti Gritti, Eliana Rulli, Maurizio D'Incalci, Daniela Rubino, Annamaria Ferrero, Colombo, N, Zaccarelli, E, Baldoni, A, Frezzini, S, Scambia, G, Palluzzi, E, Tognon, G, Lissoni, A, Rubino, D, Ferrero, A, Farina, G, Negri, E, Pesenti Gritti, A, Galli, F, Biagioli, E, Rulli, E, Poli, D, Gerardi, C, Torri, V, Fossati, R, and D'Incalci, M

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Bevacizumab, Phases of clinical research, Kaplan-Meier Estimate, Carcinoma, Ovarian Epithelial, Article, Carboplatin, Efficacy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Ovarian cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Progression-free survival, Survival rate, Trabectedin, 030304 developmental biology, Aged, Ovarian Neoplasms, Gynaecological cancer, 0303 health sciences, business.industry, Middle Aged, Progression-Free Survival, Clinical trial, Survival Rate, bevacizumab and trabectedin, chemistry, 030220 oncology & carcinogenesis, Female, business, medicine.drug
Abstract

Background Trabectedin, in addition to its antiproliferative effect, can modify the tumour microenvironment and this could be synergistic with bevacizumab. The efficacy and safety of trabectedin and bevacizumab ± carboplatin have never been investigated. Methods In this phase 2 study, women progressing between 6 and 12 months since their last platinum-based therapy were randomised to Arm BT: bevacizumab, trabectedin every 21 days, or Arm BT+C: bevacizumab, trabectedin and carboplatin every 28 days, from cycles 1 to 6, then trabectedin and bevacizumab as in Arm BT. Primary endpoints were progression-free survival rate (PFS-6) and severe toxicity rate (ST-6) at 6 months, assuming a PFS-6 ≤35% for BT and ≤40% for BT+C as not of therapeutic interest and, for both arms, a ST-6 ≥ 30% as unacceptable. Results BT+C (21 patients) did not meet the safety criteria for the second stage (ST-6 45%; 95%CI: 23%–69%) but PFS-6 was 85% (95%CI: 62%–97%). BT (50 patients) had 75% PFS-6 (95%CI: 60%–87%) and 16% ST-6 (95%CI 7%–30%). Conclusions BT compared favourably with other platinum- and non-platinum-based regimens. The combination with carboplatin needs to be assessed further in a re-modulated safer schedule to confirm its apparent strong activity. Clinical Trial Registration NCT01735071 (Clinicaltrials.gov).

Published
2019

25. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial

Author

De Placido, S, Gallo, C, De Laurentiis, M, Bisagni, G, Arpino, G, Sarobba, M, Riccardi, F, Russo, A, Del Mastro, L, Cogoni, A, Cognetti, F, Gori, S, Foglietta, J, Frassoldati, A, Amoroso, D, Laudadio, L, Moscetti, L, Montemurro, F, Verusio, C, Bernardo, A, Lorusso, V, Gravina, A, Moretti, G, Lauria, R, Lai, A, Mocerino, C, Rizzo, S, Nuzzo, F, Carlini, P, Perrone, F, Accurso, A, Agostara, B, Aieta, M, Alabiso, O, Alicicco, M, Amadori, D, Amaducci, L, Amiconi, G, Antuzzi, G, Ardine, M, Ardizzoia, A, Aversa, C, Badalamenti, G, Barni, S, Basurto, C, Berardi, R, Bergamasco, C, Bidoli, P, Bighin, C, Biondi, E, Boni, C, Borgonovo, K, Botta, M, Bravi, S, Bruzzi, P, Buono, G, Butera, A, Caldara, A, Candeloro, G, Cappelletti, C, Cardalesi, C, Carfora, E, Cariello, A, Carrozza, F, Carteni, G, Caruso, M, Casadei, V, Casanova, C, Castori, L, Cavanna, L, Cavazzini, G, Cazzaniga, M, Chilelli, M, Chiodini, P, Chiorrini, S, Ciardiello, F, Ciccarese, M, Cinieri, S, Clerico, M, Coccaro, M, Comande, M, Corbo, C, Cortino, G, Cusenza, S, Daniele, G, D'Arco, A, D'Auria, G, Dazzi, C, De Angelis, C, de Braud, F, De Feo, G, De Matteis, A, De Tursi, M, Di Blasio, A, di Lucca, G, Di Lullo, L, Di Rella, F, Di Renzo, G, Di Stefano, P, Di Stefano, A, Diana, A, Donati, S, Fabbri, A, Fabi, A, Faedi, M, Farina, G, Farris, A, Febbraro, A, Fedele, P, Federico, P, Ferrau, F, Ferretti, G, Ferro, A, Floriani, I, Forcignano, R, Forciniti, S, Forestieri, V, Fornari, G, Frisinghelli, M, Fusco, V, Gallizzi, G, Galvano, A, Gambardella, A, Gambi, A, Gebbia, V, Gervasi, E, Ghilardi, M, Giacobino, A, Giardina, G, Giotta, F, Giraudi, S, Giuliano, M, Grassadonia, A, Grasso, D, Grosso, F, Guizzaro, L, Incoronato, P, Incorvaia, L, Iodice, G, La Verde, N, Labonia, V, Landi, G, Latorre, A, Leonardi, V, Levaggi, A, Limite, G, Lina Bascialla, L, Livi, L, Maiello, E, Mandelli, D, Marcon, I, Menon, D, Montedoro, M, Moraca, L, Moretti, A, Morritti, M, Morselli, P, Mura, A, Mura, S, Musacchio, M, Muzio, A, Natale, D, Natoli, C, Nigro, C, Nistico, C, Nuzzo, A, Orditura, M, Orlando, L, Pacilio, C, Palumbo, G, Palumbo, R, Pasini, F, Paterno, E, Pazzola, A, Pelliccioni, S, Pensabene, M, Perroni, D, Pesenti Gritti, A, Petrelli, F, Piccirillo, M, Pinotti, G, Pogliani, C, Poli, D, Prader, S, Recchia, F, Rizzi, D, Romano, C, Rossello, R, Rossini, C, Salvucci, G, Sanna, V, Santini, A, Saracchini, S, Savastano, C, Scambia, G, Schettini, F, Schiavone, P, Schirone, A, Seles, E, Signoriello, S, Signoriello, G, Silva, R, Silvestri, A, Simeon, V, Spagnoletti, I, Tamberi, S, Teragni, C, Thalmann, V, Thomas, R, Thomas, G, Tienghi, A, Tinari, N, Tinessa, V, Tomei, F, Tonini, G, Torri, V, Traficante, D, Tudini, M, Turazza, M, Vignoli, R, Vitale, M, Zacchia, A, Zagarese, P, Zanni, A, Zavallone, L, Zavettieri, M, Zoboli, A, De Placido S., Gallo C., De Laurentiis M., Bisagni G., Arpino G., Sarobba M. G., Riccardi F., Russo A., Del Mastro L., Cogoni A. A., Cognetti F., Gori S., Foglietta J., Frassoldati A., Amoroso D., Laudadio L., Moscetti L., Montemurro F., Verusio C., Bernardo A., Lorusso V., Gravina A., Moretti G., Lauria R., Lai A., Mocerino C., Rizzo S., Nuzzo F., Carlini P., Perrone F., Accurso A., Agostara B., Aieta M., Alabiso O., Alicicco M. G., Amadori D., Amaducci L., Amiconi G., Antuzzi G., Ardine M., Ardizzoia A., Aversa C., Badalamenti G., Barni S., Basurto C., Berardi R., Bergamasco C., Bidoli P., Bighin C., Biondi E., Boni C., Borgonovo K., Botta M., Bravi S., Bruzzi P., Buono G., Butera A., Caldara A., Candeloro G., Cappelletti C., Cardalesi C., Carfora E., Cariello A., Carrozza F., Carteni G., Caruso M., Casadei V., Casanova C., Castori L., Cavanna L., Cavazzini G., Cazzaniga M., Chilelli M., Chiodini P., Chiorrini S., Ciardiello F., Ciccarese M., Cinieri S., Clerico M., Coccaro M., Comande M., Corbo C., Cortino G., Cusenza S., Daniele G., D'arco A. M., D'auria G., Dazzi C., De Angelis C., de Braud F., De Feo G., De Matteis A., De Tursi M., Di Blasio A., di Lucca G., Di Lullo L., Di Rella F., Di Renzo G., Di Stefano P., Di Stefano A., Diana A., Donati S., Fabbri A., Fabi A., Faedi M., Farina G., Farris A., Febbraro A., Fedele P., Federico P., Ferrau F., Ferretti G., Ferro A., Floriani I., Forcignano R., Forciniti S., Forestieri V., Fornari G., Frisinghelli M., Fusco V., Gallizzi G., Galvano A., Gambardella A., Gambi A., Gebbia V., Gervasi E., Ghilardi M., Giacobino A., Giardina G., Giotta F., Giraudi S., Giuliano M., Grassadonia A., Grasso D., Grosso F., Guizzaro L., Incoronato P., Incorvaia L., Iodice G., La Verde N., Labonia V., Landi G., Latorre A., Leonardi V., Levaggi A., Limite G., Lina Bascialla L., Livi L., Maiello E., Mandelli D., Marcon I., Menon D., Montedoro M., Moraca L., Moretti A., Morritti M. G., Morselli P., Mura A., Mura S., Musacchio M., Muzio A., Natale D., Natoli C., Nigro C., Nistico C., Nuzzo A., Orditura M., Orlando L., Pacilio C., Palumbo G., Palumbo R., Pasini F., Paterno E., Pazzola A., Pelliccioni S., Pensabene M., Perroni D., Pesenti Gritti A., Petrelli F., Piccirillo M. C., Pinotti G., Pogliani C., Poli D., Prader S., Recchia F., Rizzi D., Romano C., Rossello R., Rossini C., Salvucci G., Sanna V., Santini A., Saracchini S., Savastano C., Scambia G., Schettini F., Schiavone P., Schirone A., Seles E., Signoriello S., Signoriello G., Silva R. R., Silvestri A., Simeon V., Spagnoletti I., Tamberi S., Teragni C., Thalmann V., Thomas R., Thomas G., Tienghi A., Tinari N., Tinessa V., Tomei F., Tonini G., Torri V., Traficante D., Tudini M., Turazza M., Vignoli R., Vitale M. G., Zacchia A., Zagarese P., Zanni A., Zavallone L., Zavettieri M., Zoboli A., De Placido, S, Gallo, C, De Laurentiis, M, Bisagni, G, Arpino, G, Sarobba, M, Riccardi, F, Russo, A, Del Mastro, L, Cogoni, A, Cognetti, F, Gori, S, Foglietta, J, Frassoldati, A, Amoroso, D, Laudadio, L, Moscetti, L, Montemurro, F, Verusio, C, Bernardo, A, Lorusso, V, Gravina, A, Moretti, G, Lauria, R, Lai, A, Mocerino, C, Rizzo, S, Nuzzo, F, Carlini, P, Perrone, F, Accurso, A, Agostara, B, Aieta, M, Alabiso, O, Alicicco, M, Amadori, D, Amaducci, L, Amiconi, G, Antuzzi, G, Ardine, M, Ardizzoia, A, Aversa, C, Badalamenti, G, Barni, S, Basurto, C, Berardi, R, Bergamasco, C, Bidoli, P, Bighin, C, Biondi, E, Boni, C, Borgonovo, K, Botta, M, Bravi, S, Bruzzi, P, Buono, G, Butera, A, Caldara, A, Candeloro, G, Cappelletti, C, Cardalesi, C, Carfora, E, Cariello, A, Carrozza, F, Carteni, G, Caruso, M, Casadei, V, Casanova, C, Castori, L, Cavanna, L, Cavazzini, G, Cazzaniga, M, Chilelli, M, Chiodini, P, Chiorrini, S, Ciardiello, F, Ciccarese, M, Cinieri, S, Clerico, M, Coccaro, M, Comande, M, Corbo, C, Cortino, G, Cusenza, S, Daniele, G, D'Arco, A, D'Auria, G, Dazzi, C, De Angelis, C, de Braud, F, De Feo, G, De Matteis, A, De Tursi, M, Di Blasio, A, di Lucca, G, Di Lullo, L, Di Rella, F, Di Renzo, G, Di Stefano, P, Di Stefano, A, Diana, A, Donati, S, Fabbri, A, Fabi, A, Faedi, M, Farina, G, Farris, A, Febbraro, A, Fedele, P, Federico, P, Ferrau, F, Ferretti, G, Ferro, A, Floriani, I, Forcignano, R, Forciniti, S, Forestieri, V, Fornari, G, Frisinghelli, M, Fusco, V, Gallizzi, G, Galvano, A, Gambardella, A, Gambi, A, Gebbia, V, Gervasi, E, Ghilardi, M, Giacobino, A, Giardina, G, Giotta, F, Giraudi, S, Giuliano, M, Grassadonia, A, Grasso, D, Grosso, F, Guizzaro, L, Incoronato, P, Incorvaia, L, Iodice, G, La Verde, N, Labonia, V, Landi, G, Latorre, A, Leonardi, V, Levaggi, A, Limite, G, Lina Bascialla, L, Livi, L, Maiello, E, Mandelli, D, Marcon, I, Menon, D, Montedoro, M, Moraca, L, Moretti, A, Morritti, M, Morselli, P, Mura, A, Mura, S, Musacchio, M, Muzio, A, Natale, D, Natoli, C, Nigro, C, Nistico, C, Nuzzo, A, Orditura, M, Orlando, L, Pacilio, C, Palumbo, G, Palumbo, R, Pasini, F, Paterno, E, Pazzola, A, Pelliccioni, S, Pensabene, M, Perroni, D, Pesenti Gritti, A, Petrelli, F, Piccirillo, M, Pinotti, G, Pogliani, C, Poli, D, Prader, S, Recchia, F, Rizzi, D, Romano, C, Rossello, R, Rossini, C, Salvucci, G, Sanna, V, Santini, A, Saracchini, S, Savastano, C, Scambia, G, Schettini, F, Schiavone, P, Schirone, A, Seles, E, Signoriello, S, Signoriello, G, Silva, R, Silvestri, A, Simeon, V, Spagnoletti, I, Tamberi, S, Teragni, C, Thalmann, V, Thomas, R, Thomas, G, Tienghi, A, Tinari, N, Tinessa, V, Tomei, F, Tonini, G, Torri, V, Traficante, D, Tudini, M, Turazza, M, Vignoli, R, Vitale, M, Zacchia, A, Zagarese, P, Zanni, A, Zavallone, L, Zavettieri, M, Zoboli, A, De Placido S., Gallo C., De Laurentiis M., Bisagni G., Arpino G., Sarobba M. G., Riccardi F., Russo A., Del Mastro L., Cogoni A. A., Cognetti F., Gori S., Foglietta J., Frassoldati A., Amoroso D., Laudadio L., Moscetti L., Montemurro F., Verusio C., Bernardo A., Lorusso V., Gravina A., Moretti G., Lauria R., Lai A., Mocerino C., Rizzo S., Nuzzo F., Carlini P., Perrone F., Accurso A., Agostara B., Aieta M., Alabiso O., Alicicco M. G., Amadori D., Amaducci L., Amiconi G., Antuzzi G., Ardine M., Ardizzoia A., Aversa C., Badalamenti G., Barni S., Basurto C., Berardi R., Bergamasco C., Bidoli P., Bighin C., Biondi E., Boni C., Borgonovo K., Botta M., Bravi S., Bruzzi P., Buono G., Butera A., Caldara A., Candeloro G., Cappelletti C., Cardalesi C., Carfora E., Cariello A., Carrozza F., Carteni G., Caruso M., Casadei V., Casanova C., Castori L., Cavanna L., Cavazzini G., Cazzaniga M., Chilelli M., Chiodini P., Chiorrini S., Ciardiello F., Ciccarese M., Cinieri S., Clerico M., Coccaro M., Comande M., Corbo C., Cortino G., Cusenza S., Daniele G., D'arco A. M., D'auria G., Dazzi C., De Angelis C., de Braud F., De Feo G., De Matteis A., De Tursi M., Di Blasio A., di Lucca G., Di Lullo L., Di Rella F., Di Renzo G., Di Stefano P., Di Stefano A., Diana A., Donati S., Fabbri A., Fabi A., Faedi M., Farina G., Farris A., Febbraro A., Fedele P., Federico P., Ferrau F., Ferretti G., Ferro A., Floriani I., Forcignano R., Forciniti S., Forestieri V., Fornari G., Frisinghelli M., Fusco V., Gallizzi G., Galvano A., Gambardella A., Gambi A., Gebbia V., Gervasi E., Ghilardi M., Giacobino A., Giardina G., Giotta F., Giraudi S., Giuliano M., Grassadonia A., Grasso D., Grosso F., Guizzaro L., Incoronato P., Incorvaia L., Iodice G., La Verde N., Labonia V., Landi G., Latorre A., Leonardi V., Levaggi A., Limite G., Lina Bascialla L., Livi L., Maiello E., Mandelli D., Marcon I., Menon D., Montedoro M., Moraca L., Moretti A., Morritti M. G., Morselli P., Mura A., Mura S., Musacchio M., Muzio A., Natale D., Natoli C., Nigro C., Nistico C., Nuzzo A., Orditura M., Orlando L., Pacilio C., Palumbo G., Palumbo R., Pasini F., Paterno E., Pazzola A., Pelliccioni S., Pensabene M., Perroni D., Pesenti Gritti A., Petrelli F., Piccirillo M. C., Pinotti G., Pogliani C., Poli D., Prader S., Recchia F., Rizzi D., Romano C., Rossello R., Rossini C., Salvucci G., Sanna V., Santini A., Saracchini S., Savastano C., Scambia G., Schettini F., Schiavone P., Schirone A., Seles E., Signoriello S., Signoriello G., Silva R. R., Silvestri A., Simeon V., Spagnoletti I., Tamberi S., Teragni C., Thalmann V., Thomas R., Thomas G., Tienghi A., Tinari N., Tinessa V., Tomei F., Tonini G., Torri V., Traficante D., Tudini M., Turazza M., Vignoli R., Vitale M. G., Zacchia A., Zagarese P., Zanni A., Zavallone L., Zavettieri M., and Zoboli A.

Abstract

Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is regist

Published
2018

28. CoSMed: A Confidentiality-Verified Social Media Platform

Author

Bauereiß, T., Pesenti Gritti, A., Popescu, A., Raimondi, F., Popescu, Andrei [0000-0001-8747-0619], and Apollo - University of Cambridge Repository

Subjects
46 Information and Computing Sciences, 4604 Cybersecurity and Privacy
Abstract

This paper describes progress with our agenda of formal verification of information flow security for realistic systems. We present CoSMed, a social media platform with verified document confidentiality. The system’s kernel is implemented and verified in the proof assistant Isabelle/HOL. For verification, we employ the framework of Bounded-De- ducibility (BD) Security, previously introduced for the conference system CoCon. CoSMed is a second major case study in this framework. For CoSMed, the static topology of declas- sification bounds and triggers that characterized previous instances of BD Security has to give way to a dynamic integration of the triggers as part of the bounds. We also show that, from a theoretical viewpoint, the removal of triggers from the notion of BD Security does not restrict its expressiveness.

Published
2018

32. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial

Author

De Placido, Sabino, primary, Gallo, Ciro, additional, De Laurentiis, Michelino, additional, Bisagni, Giancarlo, additional, Arpino, Grazia, additional, Sarobba, Maria Giuseppa, additional, Riccardi, Ferdinando, additional, Russo, Antonio, additional, Del Mastro, Lucia, additional, Cogoni, Alessio Aligi, additional, Cognetti, Francesco, additional, Gori, Stefania, additional, Foglietta, Jennifer, additional, Frassoldati, Antonio, additional, Amoroso, Domenico, additional, Laudadio, Lucio, additional, Moscetti, Luca, additional, Montemurro, Filippo, additional, Verusio, Claudio, additional, Bernardo, Antonio, additional, Lorusso, Vito, additional, Gravina, Adriano, additional, Moretti, Gabriella, additional, Lauria, Rossella, additional, Lai, Antonella, additional, Mocerino, Carmela, additional, Rizzo, Sergio, additional, Nuzzo, Francesco, additional, Carlini, Paolo, additional, Perrone, Francesco, additional, Accurso, Antonello, additional, Agostara, Biagio, additional, Aieta, Michele, additional, Alabiso, Oscar, additional, Alicicco, Maria Grazia, additional, Amadori, Dino, additional, Amaducci, Laura, additional, Amiconi, Gianna, additional, Antuzzi, Giustino, additional, Ardine, Mara, additional, Ardizzoia, Antonio, additional, Aversa, Caterina, additional, Badalamenti, Giuseppe, additional, Barni, Sandro, additional, Basurto, Carlo, additional, Berardi, Rossana, additional, Bergamasco, Cinzia, additional, Bidoli, Paolo, additional, Bighin, Claudia, additional, Biondi, Edoardo, additional, Boni, Corrado, additional, Borgonovo, Karen, additional, Botta, Mario, additional, Bravi, Stefano, additional, Bruzzi, Paolo, additional, Buono, Giuseppe, additional, Butera, Alfredo, additional, Caldara, Alessia, additional, Candeloro, Giampiero, additional, Cappelletti, Claudia, additional, Cardalesi, Cinzia, additional, Carfora, Elisabetta, additional, Cariello, Anna, additional, Carrozza, Francesco, additional, Cartenì, Giacomo, additional, Caruso, Michele, additional, Casadei, Virginia, additional, Casanova, Claudia, additional, Castori, Luigi, additional, Cavanna, Luigi, additional, Cavazzini, Giovanna, additional, Cazzaniga, Marina, additional, Chilelli, Mario, additional, Chiodini, Paolo, additional, Chiorrini, Silvia, additional, Ciardiello, Fortunato, additional, Ciccarese, Mariangela, additional, Cinieri, Saverio, additional, Clerico, Mario, additional, Coccaro, Mariarosa, additional, Comande, Mario, additional, Corbo, Claudia, additional, Cortino, Giuseppina, additional, Cusenza, Stefania, additional, Daniele, Gennaro, additional, D'arco, Alfonso Maria, additional, D'auria, Giuliana, additional, Dazzi, Claudio, additional, De Angelis, Carmine, additional, de Braud, Filippo, additional, De Feo, Gianfranco, additional, De Matteis, Andrea, additional, De Tursi, Michele, additional, Di Blasio, Anna, additional, di Lucca, Giuseppe, additional, Di Lullo, Liberato, additional, Di Rella, Francesca, additional, Di Renzo, Gianfranco, additional, Di Stefano, Pia, additional, Di Stefano, Aida, additional, Diana, Anna, additional, Donati, Sara, additional, Fabbri, Agnese, additional, Fabi, Alessandra, additional, Faedi, Marina, additional, Farina, Gabriella, additional, Farris, Antonio, additional, Febbraro, Antonio, additional, Fedele, Palma, additional, Federico, Piera, additional, Ferraù, Francesco, additional, Ferretti, Gianluigi, additional, Ferro, Antonella, additional, Floriani, Irene, additional, Forcignanò, Rosachiara, additional, Forciniti, Samantha, additional, Forestieri, Valeria, additional, Fornari, Gianni, additional, Frisinghelli, Michela, additional, Fusco, Vittorio, additional, Gallizzi, Giulia, additional, Galvano, Antonio, additional, Gambardella, Antonio, additional, Gambi, Angelo, additional, Gebbia, Vittorio, additional, Gervasi, Erika, additional, Ghilardi, Mara, additional, Giacobino, Alice, additional, Giardina, Giovanni, additional, Giotta, Francesco, additional, Giraudi, Sara, additional, Giuliano, Mario, additional, Grassadonia, Antonino, additional, Grasso, Donatella, additional, Grosso, Federica, additional, Guizzaro, Lorenzo, additional, Incoronato, Pasquale, additional, Incorvaia, Lorena, additional, Iodice, Giovanni, additional, La Verde, Nicla, additional, Labonia, Vincenzo, additional, Landi, Gabriella, additional, Latorre, Agnese, additional, Leonardi, Vita, additional, Levaggi, Alessia, additional, Limite, Gennaro, additional, Lina Bascialla, Linda, additional, Livi, Lorenzo, additional, Maiello, Evaristo, additional, Mandelli, Daniela, additional, Marcon, Ilaria, additional, Menon, Daniela, additional, Montedoro, Michele, additional, Moraca, Lucia, additional, Moretti, Anna, additional, Morritti, Maria Grazia, additional, Morselli, Patrizia, additional, Mura, Antonella, additional, Mura, Silvia, additional, Musacchio, Michela, additional, Muzio, Alberto, additional, Natale, Donato, additional, Natoli, Clara, additional, Nigro, Cinzia, additional, Nisticò, Cecilia, additional, Nuzzo, Antonio, additional, Orditura, Michele, additional, Orlando, Laura, additional, Pacilio, Carmen, additional, Palumbo, Giuliano, additional, Palumbo, Raffaella, additional, Pasini, Felice, additional, Paterno, Emanuela, additional, Pazzola, Antonio, additional, Pelliccioni, Silvia, additional, Pensabene, Matilde, additional, Perroni, Davide, additional, Pesenti Gritti, Angela, additional, Petrelli, Fausto, additional, Piccirillo, Maria Carmela, additional, Pinotti, Graziella, additional, Pogliani, Claudia, additional, Poli, Davide, additional, Prader, Sonia, additional, Recchia, Francesco, additional, Rizzi, Daniele, additional, Romano, Carmen, additional, Rossello, Rosalba, additional, Rossini, Chiara, additional, Salvucci, Giuseppina, additional, Sanna, Valeria, additional, Santini, Alessandra, additional, Saracchini, Silvana, additional, Savastano, Clementina, additional, Scambia, Giovanni, additional, Schettini, Francesco, additional, Schiavone, Paola, additional, Schirone, Alessio, additional, Seles, Elena, additional, Signoriello, Simona, additional, Signoriello, Giuseppe, additional, Silva, Rosa Rita, additional, Silvestri, Antonia, additional, Simeon, Vittorio, additional, Spagnoletti, Ilaria, additional, Tamberi, Stefano, additional, Teragni, Cristina, additional, Thalmann, Verena, additional, Thomas, Renato, additional, Thomas, Guglielmo, additional, Tienghi, Amelia, additional, Tinari, Nicola, additional, Tinessa, Vincenza, additional, Tomei, Federica, additional, Tonini, Giuseppe, additional, Torri, Valter, additional, Traficante, Divina, additional, Tudini, Marianna, additional, Turazza, Monica, additional, Vignoli, Roberto, additional, Vitale, Maria Giuseppa, additional, Zacchia, Alessandra, additional, Zagarese, Pasquale, additional, Zanni, Alda, additional, Zavallone, Laura, additional, Zavettieri, Maria, additional, and Zoboli, Alessandra, additional

Published
2018
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34. Psychometric Properties of the Social Phobia and Anxiety Inventory for Children (SPAI-C)

Author

Marco Battaglia, Valentina Lampis, Annalisa Zanoni, Paola Pesenti-Gritti, Simona Scaini, Chiara A. M. Spatola, Michael J. Kofler, Deborah C. Beidel, and Anna Ogliari

Subjects
COMORBIDITY SURVEY REPLICATION, Psychometrics, NORMATIVE DATA, media_common.quotation_subject, Population, CHILDHOOD ANXIETY, Test validity, Settore M-PSI/03 - PSICOMETRIA, Developmental psychology, ADOLESCENTS, medicine, Assertiveness, education, DEVELOPMENTAL ISSUES, Applied Psychology, CONSTRUCT-VALIDITY, media_common, education.field_of_study, DSM-IV DISORDERS, Social anxiety, Construct validity, medicine.disease, DISCRIMINATIVE VALIDITY, RISK-FACTORS, SCREEN, Anxiety, medicine.symptom, Psychology, Anxiety disorder
Abstract

Reliable and valid self-report questionnaires could be useful as initial screening instruments for social phobia in both clinical settings and general populations. The present study investigates the factor structure and psychometric properties of the Social Phobia and Anxiety Inventory for Children (SPAI-C) in a sample of 228 children from the Italian general population aged 8 to 11. The children were asked to complete the Italian version of the SPAI-C and the Screen for Child Anxiety Related Emotional Disorders (SCARED) questionnaire. Confirmatory factor analyses revealed that social phobia can be conceptualized as a unitary construct consisting of five distinct but interrelated symptom clusters named Assertiveness, General Conversation, Physical/Cognitive Symptoms, Avoidance, and Public Performance. Internal consistency of the SPAI-C total scores and two subscales was good; correlations between SPAI-C total scores and SCARED total scores/subscales ranged from moderate to high (Generalized Anxiety Disorder, for social phobia), with the SCARED Social Phobia subscale as the best predictor of SPAI-C total scores. The results indicate that the SPAI-C is a reliable and sensitive instrument suitable for identifying Social Phobia in the young Italian general population.

Published
2012
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35. Gene-environment interactions in panic disorder and CO2 sensitivity: Effects of events occurring early in life

Author

Anna Ogliari, Chiara A. M. Spatola, Paola Pesenti-Gritti, Simona Scaini, Kristian Tambs, Sara Moruzzi, Marco Battaglia, and Sarah E. Medland

Subjects
education.field_of_study, Panic disorder, Population, Panic, Context (language use), Biology, medicine.disease, Cellular and Molecular Neuroscience, Psychiatry and Mental health, Endophenotype, Trait, medicine, Young adult, medicine.symptom, education, Genetics (clinical), Anxiety disorder, Demography
Abstract

Heterogeneous life events (LE) precede the onset of-and potentially increase the susceptibility to-panic disorder (PD). It remains unknown whether LE can act as moderators in the context of gene-by-environment interactions (G×E) that alter the susceptibility to PD and the related trait of CO sensitivity, nor it is known whether such moderation may depend on occurrence of events at different epochs in life. In 712 general population twins we analyzed by Maximum Likelihood analyses of ordinal data whether life (major- and stressful) events moderate the genetic risk for PD and CO sensitivity, as indexed by the 35% CO/65% O challenge. For CO sensitivity, best-fitting models encompassed both additive and interactional effects that increased linearly with the cumulative number and severity (SEV) of events in lifetime. By analyzing the moderation effect of cumulative SEV separately for events that had occurred in adulthood (between age 18 and 37) or during childhood-adolescence (before the 18th birthday), we found evidence of G×E only within the childhood-adolescence window of risk, although twins had rated the childhood-adolescence events as significantly (P=0.001) less severe than those having occurred during adulthood. For PD, all interactional terms could be dropped without significant worsening of the models' fit. Consistently with a diathesis-stress model, LE appear to act as moderators of the genetic variance for CO sensitivity. Childhood-adolescence appears to constitute a sensitive period to the action of events that concur to alter the susceptibility to this panic-related trait.

Published
2010
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37. [The ciliopathies--Polycystic Kidney Disease]

Author

Angela Pesenti, Gritti and Alessandra, Boletta

Subjects
Polycystic Kidney Diseases, Humans, Ciliary Motility Disorders
Abstract

The primary cilium is an organelle composed of microtubules that emerges from the cell surface. Its inappropriate structure or function leads to the onset of a series of disease conditions collectively defined as ciliopathies, a class of genetic disorders with a variety of manifestations in different organs. In the kidneys the ciliopathies manifest with renal cysts and propotype diseases are autosomal dominant and autosomal recessive polycystic kidney diseases (ADPKD and ARPKD, respectively) . ADPKD is one of the most frequent genetic disorders affecting 1: 500 to 1: 1000 at birth. It manifests primarily with the formation of cysts in both kidneys that increase in number and size during the life of an individual, eventually causing loss of renal function. ADPKD is caused by mutations in the genes PKD1 (85% of cases) or PKD2 (15% of cases), encoding for polycystin-1 (PC-1) and polycystin-2 (PC-2) respectively. The PC-1/PC-2 complex was found on the primary cilium and elsewhere. Here we summarize recent work from our and other labs suggesting that defective planar cell polarity and cellular shape might underly PKD and additional work suggesting that defective glucose metabolism is a feature of this disease. This is the summary of a presentation delivered during a recent meeting on the genetics of renal diseases.

Published
2015

40. Unstable maternal environment, separation anxiety, and heightened CO2 sensitivity induced by gene-by-environment interplay

Author

Paola Pesenti-Gritti, Francesca R. D'Amato, Rossella Ventura, Roberto Coccurello, Anna Moles, Chiara A. M. Spatola, Claudio Zanettini, Diego Oddi, Tiziana Pascucci, Stefano Puglisi-Allegra, Valentina Lampis, Marco Battaglia, D’Amato, F, Zanettini, C, Lampis, V, Coccurello, R, Pascucci, T, Ventura, R, Puglisi Allegra, S, Spatola, Cam, Pesenti Gritti, P, Oddi, D, Moles, A, and Battaglia, MARCO MARIA

Subjects
Male, Aging, Anatomy and Physiology, Heredity, Mouse, Settore M-PSI/02 - PSICOBIOLOGIA E PSICOLOGIA FISIOLOGICA, Respiratory System, lcsh:Medicine, Physiology, Social and Behavioral Sciences, Mice, Behavioral Neuroscience, Anxiety, Separation, Psychology, panic disorder, lcsh:Science, Tidal volume, Psychiatry, Child Psychiatry, Multidisciplinary, Behavior, Animal, Respiration, Separation anxiety disorder, Animal Models, Anxiety Disorders, Phenotype, Mental Health, Anxiety, Medicine, Female, medicine.symptom, Research Article, Biology, Environment, Model Organisms, Developmental Neuroscience, Neuropsychology, medicine, Tidal Volume, Genetics, Animals, Humans, Respiratory Physiology, Mood Disorders, Panic disorder, lcsh:R, Panic, Reproducibility of Results, panic disorder, separation anxiety, Heritability, Carbon Dioxide, medicine.disease, separation anxiety, Genes, Developmental Psychology, lcsh:Q, Licking, Corticosterone, Animal Genetics, Respiratory minute volume, Neuroscience
Abstract

Background In man, many different events implying childhood separation from caregivers/unstable parental environment are associated with heightened risk for panic disorder in adulthood. Twin data show that the occurrence of such events in childhood contributes to explaining the covariation between separation anxiety disorder, panic, and the related psychobiological trait of CO2 hypersensitivity. We hypothesized that early interference with infant-mother interaction could moderate the interspecific trait of response to CO2 through genetic control of sensitivity to the environment. Methodology Having spent the first 24 hours after birth with their biological mother, outbred NMRI mice were cross-fostered to adoptive mothers for the following 4 post-natal days. They were successively compared to normally-reared individuals for: number of ultrasonic vocalizations during isolation, respiratory physiology responses to normal air (20%O2), CO2-enriched air (6% CO2), hypoxic air (10%O2), and avoidance of CO2-enriched environments. Results Cross-fostered pups showed significantly more ultrasonic vocalizations, more pronounced hyperventilatory responses (larger tidal volume and minute volume increments) to CO2-enriched air and heightened aversion towards CO2-enriched environments, than normally-reared individuals. Enhanced tidal volume increment response to 6%CO2 was present at 16–20, and 75–90 postnatal days, implying the trait's stability. Quantitative genetic analyses of unrelated individuals, sibs and half-sibs, showed that the genetic variance for tidal volume increment during 6%CO2 breathing was significantly higher (Bartlett χ = 8.3, p = 0.004) among the cross-fostered than the normally-reared individuals, yielding heritability of 0.37 and 0.21 respectively. These results support a stress-diathesis model whereby the genetic influences underlying the response to 6%CO2 increase their contribution in the presence of an environmental adversity. Maternal grooming/licking behaviour, and corticosterone basal levels were similar among cross-fostered and normally-reared individuals. Conclusions A mechanism of gene-by-environment interplay connects this form of early perturbation of infant-mother interaction, heightened CO2 sensitivity and anxiety. Some non-inferential physiological measurements can enhance animal models of human neurodevelopmental anxiety disorders.

Published
2010

49. Genetic Study of the Acute Anxious Response to Carbon Dioxide Stimulation in Man

Author

BATTAGLIA, MARCO MARIA, OGLIARI, ANNA LUCIA, HARRIS J, SPATOLA CAM, PESENTI GRITTI P, REICHBORN KJENNERUD T, TORGERSEN S, KRINGLEN E, TAMBS K. A., Battaglia, MARCO MARIA, Ogliari, ANNA LUCIA, Harris, J, Spatola, Cam, PESENTI GRITTI, P, REICHBORN KJENNERUD, T, Torgersen, S, Kringlen, E, and Tambs, K. A.

Published
2007

50. Gene-Environment Interactions in Panic Disorder and CO₂ Sensitivity: Effects of Events Occurring Early in Life

Author

Chiara A M, Spatola, Simona, Scaini, Paola, Pesenti-Gritti, Sarah E, Medland, Sara, Moruzzi, Anna, Ogliari, Kristian, Tambs, and Marco, Battaglia

Subjects
Adult, Models, Genetic, Twins, Settore M-PSI/08 - PSICOLOGIA CLINICA, Environment, Carbon Dioxide, Childhood, Life Change Events, Young Adult, Endophenotype, Genetic, Models, Genetics, Humans, Panic Disorder, Childhood, Endophenotype, Genetics, Twins
Abstract

Heterogeneous life events (LE) precede the onset of-and potentially increase the susceptibility to-panic disorder (PD). It remains unknown whether LE can act as moderators in the context of gene-by-environment interactions (G×E) that alter the susceptibility to PD and the related trait of CO₂ sensitivity, nor it is known whether such moderation may depend on occurrence of events at different epochs in life. In 712 general population twins we analyzed by Maximum Likelihood analyses of ordinal data whether life (major- and stressful) events moderate the genetic risk for PD and CO₂ sensitivity, as indexed by the 35% CO₂ /65% O₂ challenge. For CO₂ sensitivity, best-fitting models encompassed both additive and interactional effects that increased linearly with the cumulative number and severity (SEV) of events in lifetime. By analyzing the moderation effect of cumulative SEV separately for events that had occurred in adulthood (between age 18 and 37) or during childhood-adolescence (before the 18th birthday), we found evidence of G×E only within the childhood-adolescence window of risk, although twins had rated the childhood-adolescence events as significantly (P = 0.001) less severe than those having occurred during adulthood. For PD, all interactional terms could be dropped without significant worsening of the models' fit. Consistently with a diathesis-stress model, LE appear to act as moderators of the genetic variance for CO₂ sensitivity. Childhood-adolescence appears to constitute a sensitive period to the action of events that concur to alter the susceptibility to this panic-related trait.

Published
2011

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