المؤلفون: Rita Emilena Saladino, Rocco Giannicola, Rita Agostino, Nicoletta Staropoli, Alessandra Strangio, Teresa Del Giudice, Maria Altomonte, Paolo Tini, Antonia Consuelo Falzea, Natale Imbesi, Valentina Arcati, Giuseppa Romeo, Daniele Caracciolo, Amalia Luce, Michele Caraglia, Antonio Giordano, Alois Necas, Evzen Amler, Vito Barbieri, Pierfrancesco Tassone

المصدر: Journal for ImmunoTherapy of Cancer, Vol 8, Iss 1 (2020)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background Nivolumab is a human monoclonal antibody against programmed cell death receptor-1 (PD-1) able to rescue quiescent tumor infiltrating cytotoxic T lymphocytes (CTLs) restoring their ability to kill target cells expressing specific tumor antigen-derived epitope peptides bound to homologue human leukocyte antigen (HLA) molecules. Nivolumab is currently an active but expensive therapeutic agent for metastatic non-small cell lung cancer (mNSCLC), producing, in some cases, immune-related adverse events (irAEs). At the present, no reliable biomarkers have been validated to predict either treatment response or adverse events in treated patients.Methods We performed a retrospective multi-institutional analysis including 119 patients with mNSCLC who received PD-1 blockade since November 2015 to investigate the predictive role of germinal class I HLA and DRB1 genotype. We investigated the correlation among patients’ outcome and irAEs frequency with specific HLA A, B, C and DRB1 alleles by reverse sequence-specific oligonucleotide (SSO) DNA typing.Results A poor outcome in patients negative for the expression of two most frequent HLA-A alleles was detected (HLA: HLA-A*01 and or A*02; progression-free survival (PFS): 7.5 (2.8 to 12.2) vs 15.9 (0 to 39.2) months, p=0.01). In particular, HLA-A*01-positive patients showed a prolonged PFS of 22.6 (10.2 to 35.0) and overall survival (OS) of 30.8 (7.7 to 53.9) months, respectively. We also reported that HLA-A and DRB1 locus heterozygosis (het) were correlated to a worse OS if we considered het in the locus A; in reverse, long survival was correlated to het in DRB1.Conclusions This study demonstrate that class I and II HLA allele characterization to define tumor immunogenicity has relevant implications in predicting nivolumab efficacy in mNSCLC and provide the rationale for further prospective trials of cancer immunotherapy.

وصف الملف: electronic resource

العلاقة: https://jitc.bmj.com/content/8/1/e000733.fullTest; https://doaj.org/toc/2051-1426Test

الوصول الحر: https://doaj.org/article/903b06629eeb4b71bbf87b7168ef20f5Test

المؤلفون: Valerio Nardone, Pierpaolo Pastina, Rocco Giannicola, Rita Agostino, Stefania Croci, Paolo Tini, Luigi Pirtoli, Antonio Giordano, Pierosandro Tagliaferri, Pierpaolo Correale

المصدر: Frontiers in Immunology, Vol 9 (2018)

مصطلحات موضوعية: NSCLC, radiation therapy, immunotherapy, HNSCC, chemotherapy, Immunologic diseases. Allergy, RC581-607

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fimmu.2018.02941/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/543c0c2eca674be697007e77d6ae499cTest

المؤلفون: Antonio Clavenna, Massimo Cartabia, Maurizio Bonati, Federico Marchetti, Giorgio Tamburlini, Antonio Addis, Michele Valente, Rita Campi, Stefania Manetti, Valeria Carraro, Sergio Conti Nibali, Renato Sansone, Patrizia Rogari, Annalisa Campomori, Luca De Fiore, Renata Bortolus, Sergio Cattani, Cristiana Piloni, Valeria Renzetti, Rosario Cavallo, Gherardo Rapisardi, Giacomo Toffol, Vicenza Briscioli, Carla Cafaro, Cristoforo Cocchiara, Isodiana Crupi, Patrizia Del Balzo, Laura Dell’edera, Chiara Di Francesco, Alberto Ferrando, Francesca Grassa, Chiara Guidoni, Claudio Mangialavori, Stefano Marinoni, Francesca Marongiu, Fausta Matera, Paolo Moretti, Laura Olimpi, Angela Pasinato, Ilaria Porro, Ippolita Roncoroni, Raffaella Schiro’, Patrizia Seppia, Federica Zanetto, Anna Aloisio, Elisabetta Anedda, Giuliana Apuzzo, Giovanna Argo, Anna Armenio, Emanuela Ballerini, Monica Benedetti, Daniela Bertoli, Stefano Bollettini, Chiara Bottalico, Aurora Bottiglieri, Vincenza Briscioli, Antonella Bruno, Laura Brusadin, Mariantonietta Caiazzo, Patrizia Calamita, Miriana Callegari, Rosaria Cambria, Maria Cristina Cantù, Domenico Capomolla, Anna Caracciolo, Maria Concetta Carbone, Gaetano Carrassi, Maria Laura Cartiglia, Sara Casagranda, Ornella Castiglione, Rosario Salvatore Cavallo, Teresa Cazzato, Maria Angela Cazzuffi, Jennifer Chiarolanza, Rosaria China, Nicoletta Cimadamore, Roberto Cionini, Cristina Ciuffo, Damiano Colazzo, Anna Maria Costantini, Claudio Cravidi, Marialuisa Criscione, Rita D’Agostino, Daniela Danieli, Luigi De Carlo, Marina De Sanctis, Giuseppina De Santes, Gian Piero Del Bono, Maria Elisabetta Di Pietro, Maria Chiara Dini, Paolo Fiammengo, Micaela Foco, Maria Teresa Fonte, Maria Frigeri, Andrea Galvagno, Matteo Gaudino, Stefania Genoni, Silvia Girotto, Gianluca Gornati, Marta Gozzi, Enrica Heritier, Antonella Lavagetto, Raffaele Limauro, Alessandra Magnelli, Maria Gabriella Maiolino, Monica Malventano, Silvia Marchi, Natale Maresca, Federico Marolla, Agata Martinelli, Chiara Martinez, Nicoletta Mascarello, Carla Matiotti, Elisabetta Mazzucchi, Donatella Moggia, Manuela Musetti, Paolo Nardini, Alberto Neri, Patrizia Neri, Flavia Nicoloso, Laura Maria Olimpi, Giancarlo Ottonello, Giacinta Padula, Paolo Maria Paganuzzi, Rosanna Palazzi, Alessandra Palmero, Maria Chiara Parisini, Giovannina Pastorelli, Marilena Pavoni, Lucia Peccarisi, Antonella Pellacani, Cristina Perrera, Michela Picciotti, Ivo Picotto, Tiziana Piunti, Francesca Preziosi, Giuseppe Primavera, Miriam Prodi, Maria Letizia Rabbone, Innocenza Rafele, Laura Reali, Franziska Stefanie Rempp, Ada Riundi, Paolo Rosas, Annarita Russo, Mariagrazia Saccà, Elisabetta Sala, Francesca Sala, Francesca Santus, Vittoria Sarno, Alessandra Savino, Raffaella Schirò, Giuseppa Scornavacca, Maria Francesca Siracusano, Adelisa Spalla, Gloria Sturaro, Maria Grazia Toma, Ettore Tomagra, Maria Tortorella, Fausta Trentadue, Marina Trevisan, Silvia Tulisso, Roberta Usella, Anna Valente, Mariangela Valera, Edda Vernile, Valeria Vicario, Lucia Vignutelli, Paolo Vinci, Lucia Vizziello, Rosette Zand, Marco Zanette, Graziano Zucchi, Maria Luisa Zuccolo, Eleonora Morabito, Chiara Liz Pandolfini, Chiara Segre’, Rossella Claudia Cannavo’, Melania Maria Cera, Emma Maria Giugnini, Giovanni Giuliano Semprini

المصدر: BMJ Paediatrics Open, Vol 7, Iss 1 (2023)

مصطلحات موضوعية: Pediatrics, RJ1-570

الوصف: Objective To estimate the prevalence of overweight at 12 months in an Italian birth cohort and to identify factors related to an increased likelihood of being overweight.Methods The Italian NASCITA birth cohort was analysed. Infants were classified as underweight (

وصف الملف: electronic resource

العلاقة: https://bmjpaedsopen.bmj.com/content/7/1/e001622.fullTest; https://doaj.org/toc/2399-9772Test

الوصول الحر: https://doaj.org/article/4c6e00ed22404ddbbf94da42ce7eabd5Test

المؤلفون: Antonio Clavenna, Massimo Cartabia, Maurizio Bonati, Federico Marchetti, Giorgio Tamburlini, Antonio Addis, Michele Valente, Stefania Manetti, Valeria Carraro, Renato Sansone, Patrizia Rogari, Annalisa Campomori, Renata Bortolus, Sergio Cattani, Cristiana Piloni, Valeria Renzetti, Chiara Segré, Rosario Cavallo, Gherardo Rapisardi, Giacomo Toffol, Vicenza Briscioli, Carla Cafaro, Cristoforo Cocchiara, Isodiana Crupi, Laura Dell’edera, Alberto Ferrando, Francesca Grassa, Chiara Guidoni, Claudio Mangialavori, Stefano Marinoni, Francesca Marongiu, Fausta Matera, Paolo Moretti, Laura Olimpi, Angela Pasinato, Ilaria Porro, Ippolita Roncoroni, Raffaella Schiro’, Patrizia Seppia, Federica Zanetto, Anna Aloisio, Elisabetta Anedda, Giuliana Apuzzo, Giovanna Argo, Anna Armenio, Emanuela Ballerini, Monica Benedetti, Daniela Bertoli, Stefano Bollettini, Chiara Bottalico, Aurora Bottiglieri, Vincenza Briscioli, Antonella Bruno, Laura Brusadin, Mariantonietta Caiazzo, Patrizia Calamita, Miriana Callegari, Rosaria Cambria, Domenico Capomolla, Anna Caracciolo, Gaetano Carrassi, Sara Casagranda, Ornella Castiglione, Teresa Cazzato, Jennifer Chiarolanza, Rosaria China, Nicoletta Cimadamore, Roberto Cionini, Cristina Ciuffo, Damiano Colazzo, Claudio Cravidi, Marialuisa Criscione, Rita D’Agostino, Daniela Danieli, Paolo Fiammengo, Micaela Foco, Maria Frigeri, Andrea Galvagno, Matteo Gaudino, Stefania Genoni, Silvia Girotto, Gianluca Gornati, Marta Gozzi, Enrica Heritier, Antonella Lavagetto, Raffaele Limauro, Alessandra Magnelli, Monica Malventano, Silvia Marchi, Natale Maresca, Federico Marolla, Agata Martinelli, Chiara Martinez, Nicoletta Mascarello, Carla Matiotti, Elisabetta Mazzucchi, Donatella Moggia, Manuela Musetti, Paolo Nardini, Alberto Neri, Patrizia Neri, Flavia Nicoloso, Giancarlo Ottonello, Giacinta Padula, Rosanna Palazzi, Alessandra Palmero, Giovannina Pastorelli, Marilena Pavoni, Lucia Peccarisi, Antonella Pellacani, Cristina Perrera, Michela Picciotti, Ivo Picotto, Tiziana Piunti, Francesca Preziosi, Giuseppe Primavera, Miriam Prodi, Maria Letizia Rabbone, Innocenza Rafele, Laura Reali, Ada Riundi, Paolo Rosas, Annarita Russo, Mariagrazia Saccà, Elisabetta Sala, Francesca Sala, Francesca Santus, Vittoria Sarno, Alessandra Savino, Raffaella Schirò, Giuseppa Scornavacca, Giovanni GiulianoSemprini, Adelisa Spalla, Gloria Sturaro, Ettore Tomagra, Maria Tortorella, Fausta Trentadue, Marina Trevisan, Silvia Tulisso, Roberta Usella, Anna Valente, Mariangela Valera, Edda Vernile, Valeria Vicario, Lucia Vignutelli, Paolo Vinci, Lucia Vizziello, Rosette Zand, Marco Zanette, Graziano Zucchi, Giulia Segre, Luca DeFiore, Sergio ContiNibali, Patrizia DelBalzo, Chiara DiFrancesco, Rossella ClaudiaCannavò, Maria CristinaCantù, Maria ConcettaCarbone, Maria LauraCartiglia, Rosario SalvatoreCavallo, Maria AngelaCazzuffi, MelaniaMaria GiuseppinaCera, Anna MariaCostantini, Luigi DeCarlo, Marina DeSanctis, Giuseppina DeSantes, GianPiero DelBono, MariaElisabetta DiPietro, Maria ChiaraDini, Maria TeresaFonte, EmmaMaria LetiziaGiugnini, Maria GabriellaMaiolino, Laura MariaOlimpi, Paolo MariaPaganuzzi, Maria ChiaraParisini, Franziska StefanieRempp, Maria FrancescaSiracusano, Maria GraziaToma, Maria LuisaZuccolo

المصدر: BMJ Open, Vol 13, Iss 6 (2023)

مصطلحات موضوعية: Medicine

الوصف: Objective To assess the feasibility of the family paediatrician’s (FP) role in identifying the signs of postpartum depression in parents in time to guarantee child well-being.Design, setting and participants Data for this observational prospective study were collected within the NASCITA (NAscere e creSCere in ITAlia) cohort. During the first visit, paediatricians collected sociodemographic data regarding the parents and information about their health status, the pregnancy and the delivery. Whooley questions were administered during the first and second visits (scheduled 60–90 days after childbirth). Moreover, on the third visit (5–7 months after childbirth) the FP was asked to answer ‘yes’ or ‘no’ to a question on the parental postpartum depression, based on his knowledge and on the acquired information.Results In 2203 couples who completed the assessment, 529 mothers (19.9%), 141 fathers (6.3%) and 110 (5%) couples reported any depressive symptomatology. Of these, 141 mothers (5.3% of the total sample) and 18 fathers (0.8% of the total sample) were classified as ‘likely depressed’. An association was found between maternal postnatal depressive symptoms and having a diagnosed psychiatric disorder during pregnancy (OR 9.49, 95% CI: 3.20 to 28.17), not exclusively breastfeeding at hospital discharge (OR 1.76, 95% CI: 1.19 to 2.61) and the presence of child sleeping disorders at 3 (OR 2.46, 95% CI: 1.41 to 4.28) and 6 months (OR 2.18, 95% CI: 1.37 to 3.47). Another significant predictor of postpartum depression was being primiparous (OR 1.99, 95% CI: 1.31 to 3.02). Concerning the fathers, a significant association was reported only between likely depressed fathers and child sleeping disorders at 3 months (OR 7.64, 95% CI: 2.92 to 19.97). Moreover, having a likely depressed partner was strongly associated with depressive symptoms in fathers (OR 85.53, 95% CI 26.83 to 272.69).Conclusions The findings of this study support the feasibility of an active screening programme for parental postnatal depression during well-child visits as an integral part of postpartum care.Trial registration number NCT03894566; Pre-results.

وصف الملف: electronic resource

العلاقة: https://bmjopen.bmj.com/content/13/6/e069797.fullTest; https://doaj.org/toc/2044-6055Test

الوصول الحر: https://doaj.org/article/20ac1ffb4b5640d7b0cf721f0f7c222bTest

المؤلفون: Antonio Clavenna, Massimo Cartabia, Maurizio Bonati, Federico Marchetti, Giorgio Tamburlini, Antonio Addis, Michele Valente, Rita Campi, Stefania Manetti, Valeria Carraro, Chiara Pandolfini, Sergio Conti Nibali, Renato Sansone, Patrizia Rogari, Annalisa Campomori, Luca De Fiore, Renata Bortolus, Sergio Cattani, Cristiana Piloni, Valeria Renzetti, Chiara Segré, Rosario Cavallo, Gherardo Rapisardi, Giacomo Toffol, Vicenza Briscioli, Carla Cafaro, Cristoforo Cocchiara, Isodiana Crupi, Patrizia Del Balzo, Laura Dell’edera, Chiara Di Francesco, Alberto Ferrando, Francesca Grassa, Chiara Guidoni, Claudio Mangialavori, Stefano Marinoni, Francesca Marongiu, Fausta Matera, Paolo Moretti, Laura Olimpi, Angela Pasinato, Ilaria Porro, Ippolita Roncoroni, Raffaella Schiro’, Patrizia Seppia, Federica Zanetto, Anna Aloisio, Elisabetta Anedda, Giuliana Apuzzo, Giovanna Argo, Anna Armenio, Emanuela Ballerini, Monica Benedetti, Daniela Bertoli, Stefano Bollettini, Chiara Bottalico, Aurora Bottiglieri, Vincenza Briscioli, Antonella Bruno, Laura Brusadin, Mariantonietta Caiazzo, Patrizia Calamita, Miriana Callegari, Rosaria Cambria, Rossella Claudia Cannavò, Maria Cristina Cantù, Domenico Capomolla, Anna Caracciolo, Maria Concetta Carbone, Gaetano Carrassi, Maria Laura Cartiglia, Sara Casagranda, Ornella Castiglione, Rosario Salvatore Cavallo, Teresa Cazzato, Maria Angela Cazzuffi, Melania MariaGiuseppina Cera, Jennifer Chiarolanza, Rosaria China, Nicoletta Cimadamore, Roberto Cionini, Cristina Ciuffo, Damiano Colazzo, Anna Maria Costantini, Claudio Cravidi, Marialuisa Criscione, Rita D’Agostino, Daniela Danieli, Luigi De Carlo, Marina De Sanctis, Giuseppina De Santes, Gian Piero Del Bono, Maria Elisabetta Di Pietro, Maria Chiara Dini, Paolo Fiammengo, Micaela Foco, Maria Teresa Fonte, Maria Frigeri, Andrea Galvagno, Matteo Gaudino, Stefania Genoni, Silvia Girotto, Emma MariaLetizia Giugnini, Gianluca Gornati, Marta Gozzi, Enrica Heritier, Antonella Lavagetto, Raffaele Limauro, Alessandra Magnelli, Maria Gabriella Maiolino, Monica Malventano, Silvia Marchi, Natale Maresca, Federico Marolla, Agata Martinelli, Chiara Martinez, Nicoletta Mascarello, Carla Matiotti, Elisabetta Mazzucchi, Donatella Moggia, Manuela Musetti, Paolo Nardini, Alberto Neri, Patrizia Neri, Flavia Nicoloso, Laura Maria Olimpi, Giancarlo Ottonello, Giacinta Padula, Paolo Maria Paganuzzi, Rosanna Palazzi, Alessandra Palmero, Maria Chiara Parisini, Giovannina Pastorelli, Marilena Pavoni, Lucia Peccarisi, Antonella Pellacani, Cristina Perrera, Michela Picciotti, Ivo Picotto, Tiziana Piunti, Francesca Preziosi, Giuseppe Primavera, Miriam Prodi, Maria Letizia Rabbone, Innocenza Rafele, Laura Reali, Franziska Stefanie Rempp, Ada Riundi, Paolo Rosas, Annarita Russo, Mariagrazia Saccà, Elisabetta Sala, Francesca Sala, Francesca Santus, Vittoria Sarno, Alessandra Savino, Raffaella Schirò, Giuseppa Scornavacca, Giovanni GiulianoSemprini, Maria Francesca Siracusano, Adelisa Spalla, Gloria Sturaro, Maria Grazia Toma, Ettore Tomagra, Maria Tortorella, Fausta Trentadue, Marina Trevisan, Silvia Tulisso, Roberta Usella, Anna Valente, Mariangela Valera, Edda Vernile, Valeria Vicario, Lucia Vignutelli, Paolo Vinci, Lucia Vizziello, Rosette Zand, Marco Zanette, Graziano Zucchi, Maria Luisa Zuccolo

المصدر: BMJ Open, Vol 12, Iss 11 (2022)

مصطلحات موضوعية: Medicine

الوصف: Purpose The NASCITA Study, a national-level, population-based, prospective cohort study, was set up to better understand the early health status of Italian children, comprising their physical, cognitive and psychological development, and how it is affected by social and health determinants, including nurturing care. NASCITA will also assess geographical differences and disparities in healthcare.Participants Participating family paediatricians from throughout Italy enrolled infants born during the enrolment period (April 2019–July 2020). The 5054 newborns seen by the 139 paediatricians for at least two visits, including the first well-child visit, and for whom parental consent was given, make up the baseline population.Findings to date Mothers had a mean age at delivery of 33.0 years and tended to have a high or medium level of education (42.5% university and 41.7% high school degrees) and to be employed (69.7%). One-third (36.1%) took folic acid supplementation appropriately, and 6.5% smoked or consumed alcohol (10.0%) during pregnancy. One-third (31.7%) of deliveries were caesarean deliveries. Concerning the newborns, 5.8% had a low birth weight and 6.2% were born prematurely. The majority (87.7%) slept in the supine position, and 63.6% were exclusively breast fed at 1 month, with a decreasing north to south prevalence (χ2t 52; p

وصف الملف: electronic resource

العلاقة: https://bmjopen.bmj.com/content/12/11/e063394.fullTest; https://doaj.org/toc/2044-6055Test

الوصول الحر: https://doaj.org/article/d72a4d84028240b39f768bf6f3d54f3dTest

المؤلفون: Valerio Nardone, Rita Emilena Saladino, Pierosandro Tagliaferri, Rita Agostino, Luigi Pirtoli, Rocco Giannicola, Ciro Botta, Michele Caraglia, Pierpaolo Correale

المساهمون: Correale P., Saladino R.E., Nardone V., Giannicola R., Agostino R., Pirtoli L., Caraglia M., Botta C., Tagliaferri P., Correale, P., Saladino, R. E., Nardone, V., Giannicola, R., Agostino, R., Pirtoli, L., Caraglia, M., Botta, C., Tagliaferri, P.

المصدر: Immunotherapy. 11:1523-1526

مصطلحات موضوعية: Drug-Related Side Effects and Adverse Reactions, Programmed Cell Death 1 Receptor, Immunology, Antibodies, Monoclon al, Human leukocyte antigen, B7-H1 Antigen, Immune system, HLA Antigens, irAE, Neoplasms, Humans, Immunology and Allergy, Medicine, PD-1/PDL-1-blockade, business.industry, Antibodies, Monoclonal, Biomarker, Signature (logic), Haplotypes, Oncology, outcome, Immunotherapy, HLA allele, Drug-Related Side Effects and Adverse Reaction, business, Biomarkers

الوصف: The outstanding clinical expansion of monoclonal antibodies (mAbs) to programmed cell death receptor-1 (PD-1) (nivolumab and pembrolizumab) and PD-1 ligand-1 (PDL-1) (atezolizumab, avelumab and durvalumab) has received an increasing level of interest regarding immunotherapy and multidrug combinations, for the treatment of a number of common human malignancies. Some patients treated with these agents receive remarkable benefits in term of quality of life, progression-free (PFS) and overall survival (OS). However, a significant percentage of these patients experience immune-related adverse events (irAEs), while others present with an ultra-rapid disease progression, defined as hyperprogression. Research in to the mechanisms related to these events is an active field of investigation worldwide, whose results are expected to provide new insights to design new combinations, to identify potentially responsive patients and to prevent irAEs’ occurrence

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c70213e3b3eb8b72144bf5a6bb289900Test
https://doi.org/10.2217/imt-2019-0160Test

المؤلفون: Roberto Maisano, Giovanna Orizzonte, Giorgio Restifo, Pierpaolo Correale, Michele Caraglia, Vincenzo Dattola, Cirino Botta, Rita Agostino, Rita Emilena Saladino, Domenico Mazzacuva, Rocco Giannicola, Antonia Consuelo Falzea, Natale Daniele Calandruccio, Antonino Mafodda, Umberto Aguglia, Giovanna Bianco, Eleonora Iuliano, Vittoria Cianci

المساهمون: Botta, C., Agostino, R. M., Dattola, V., Cianci, V., Calandruccio, N. D., Bianco, G., Mafodda, A., Maisano, R., Iuliano, E., Orizzonte, G., Mazzacuva, D., Falzea, A. C., Saladino, R. E., Giannicola, R., Restifo, G., Aguglia, U., Caraglia, M., Correale, P., Botta C., Agostino R.M., Dattola V., Cianci V., Calandruccio N.D., Bianco G., Mafodda A., Maisano R., Iuliano E., Orizzonte G., Mazzacuva D., Falzea A.C., Saladino R.E., Giannicola R., Restifo G., Aguglia U., Caraglia M., Correale P.

المصدر: International Journal of Molecular Sciences, Vol 22, Iss 6246, p 6246 (2021)
International Journal of Molecular Sciences

مصطلحات موضوعية: 0301 basic medicine, Oncology, Male, Case Report, Autoimmunity, Pembrolizumab, PD1-checkpoint inhibitors, medicine.disease_cause, 0302 clinical medicine, Antineoplastic Agents, Immunological, Biology (General), HLA Antigen, Myositi, PD1-checkpoint inhibitor, Spectroscopy, Myositis, General Medicine, Computer Science Applications, Myasthenia Gravi, Chemistry, Pyridostigmine, urothelial cancer, 030220 oncology & carcinogenesis, Urinary Bladder Neoplasm, Class-I/II HLA, Myasthenia, medicine.drug, Human, medicine.medical_specialty, QH301-705.5, Prognosi, Human leukocyte antigen, Antibodies, Monoclonal, Humanized, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Internal medicine, medicine, Physical and Theoretical Chemistry, Adverse effect, Molecular Biology, QD1-999, Aged, business.industry, Organic Chemistry, Cancer, medicine.disease, Discontinuation, 030104 developmental biology, business

الوصف: Pembrolizumab (mAb to PD-1) has been recently approved for the therapy of pretreated urothelial cancer. Despite the efficacy, it is often accompanied by unpredictable and sometime severe immune-related (ir) adverse events (AEs). Here, we report the clinical and immune–biological characterization of a patient with a metastatic bladder cancer who developed myositis signs (M) and a myasthenia-like syndrome (MLS) during treatment with pembrolizumab. The patient presented an autoimmunity-associated HLA haplotype (HLA-A*02/HLA-B*08/HLA-C*07/HLA-DRB1*03) and experienced an increase in activated CD8 T-cells along the treatment. The symptomatology regressed after pembrolizumab discontinuation and a pyridostigmine and steroids-based therapy. This is the first report of concurrent M and MLS appearance in cancer patients receiving pembrolizumab. More efforts are needed to define early the risk and the clinical meaning of irAEs in this setting.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3d5f1730fa5ddbbe610ba6d945569661Test
http://hdl.handle.net/11591/462420Test

المؤلفون: Laura Ridolfi, Edoardo Francini, Pierpaolo Pastina, Guido Francini, Domenico Azzarello, Enrico Mini, Rocco Giannicola, Antonia Consuelo Falzea, Pierfrancesco Tassone, Alessandra Strangio, Luigi Pirtoli, Rita Agostino, Valerio Nardone, Nicoletta Staropoli, Antonio Giordano, Cirino Botta, P. Correale, Pierosandro Tagliaferri, Domenico Ciliberto

المصدر: Annals of Oncology. 30:v492-v493

مصطلحات موضوعية: Oncology, medicine.medical_specialty, business.industry, Phases of clinical research, Hematology, Chemotherapy regimen, Gemcitabine, Clinical trial, Regimen, FOLFOX, Median follow-up, Aldesleukin, Internal medicine, medicine, business, medicine.drug

الوصف: Background Immune-checkpoint blockade has shown anti-tumor activity in MSI mCRC patients only, thus, the research of more efficacious immunological strategies for colon cancer treatment is still open. GOLFIG, is a safe and active chemo-immunotherapy regimen designed on the basis of preclinical immune-oncological findings and evaluated in two subsequent Phase II and III trials in mCRC patients (J Clin Oncol, 2005,23:8950; J Immunother, 2014;37:26). This regimen combines gemcitabine + FOLFOX poly-chemotherapy with salgramostim (GM-CSF) and low dose sc. aldesleukin, to improve both cross-priming and T-cell effector anti-tumor response. Here we report a fifteen-year retrospective analysis of all patients undergone this therapeutic approach. Methods This is a multi-institutional real-life study including one hundred-seventy-nine mCRC patients receiving GOLFIG regimen between October 2001 and November 2018 with a median follow up of 120 months. The treatment was administered to 62 patients (GOLFIG-2 trial, EUDRACT: 2005-003458-81) as a first-line and to 117 patients as second/third-line (49 enrolled in the GOLFIG-1 phase II trial and 68 as real life). Kaplan-Meier and Cox-regression were carried-out to relate their PFS and OS with sex, age, sidedness, RAS mutational status, previous treatment lines, baseline clinical parameters and treatment-related irAEs. Results We recorded a PFS and OS of 15.3 (95%CI:10.4-20.2) and 24.6 (95%CI:19.07-30.14) months, respectively, with 10% of the patients surviving more than ten years. Patients’ outcome did not correlate with sex, sidedness and RAS. First line GOLFIG confirmed superiority over FOLFOX in term of PFS (HR = 0.58 p = 0.006) and OS (HR = 0.69, P = 0.06) (updated from GOLFIG-2 trial). Patients in first-line showed a longer PFS (HR = 0.69; p = 0.041) compared with the others, with no difference in OS. On the overall, a longer PFS and OS correlated with baseline neutrophil counts ≤ 4,500 cells/µl (HR:0.32; P = 0.003) and occurrence of irAEs (HR = 0.36; P = 0.0001) recorded in 24% of the cases. Conclusions These results confirm that the GOLFIG regimen is a reliable therapy for pretreated mCRC patients and offer the rationale to design combination trials with immune-checkpoint blockade. Clinical trial identification 1) GOLFIG-2 phase III trial; EudraCT: 2005-003458-81 2) GOLFIG-1 phase II trial; EudraCT no available, start July 2001. Legal entity responsible for the study The authors. Funding Italian Ministry of Education and Research (MIUR) (2009EHW394). Private grant from the “Associazione Culturale Federico II,” and from the “Associazione Riuniti Calabria Oncologia (ARCO)”. Disclosure All authors have declared no conflicts of interest.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::e9f1fb38259c4cbdd8f10d39572110f6Test
https://doi.org/10.1093/annonc/mdz253.030Test

المؤلفون: Antonia Consuelo Falzea, Valerio Nardone, Rocco Giannicola, Vito Barbieri, Nicoletta Staropoli, Graziella Calabrese, Graziella D'Arrigo, Marika Monoriti, Cirino Botta, Pierfrancesco Tassone, Pierosandro Tagliaferri, Pietro Del Medico, Pierpaolo Correale, Giovanni Tripepi, Pierpaolo Pastina, Teresa Del Giudice, Rita Agostino, Luigi Pirtoli

المساهمون: Giannicola R., D'arrigo G., Botta C., Agostino R., Del Medico P., Falzea A.C., Barbieri V., Staropoli N., Del Giudice T., Pastina P., Nardone V., Monoriti M., Calabrese G., Tripepi G., Pirtoli L., Tassone P., Tagliaferri P., Correale P., Giannicola, R, D'Arrigo, G, Botta, C, Agostino, R, Del Medico, P, Falzea, Ac, Barbieri, V, Staropoli, N, Del Giudice, T, Pastina, P, Nardone, V, Monoriti, M, Calabrese, G, Tripepi, G, Pirtoli, L, Tassone, P, Tagliaferri, P, Correale, P

مصطلحات موضوعية: Oncology, Cancer Research, medicine.medical_specialty, IrAE, Extractable nuclear antigens, medicine.medical_treatment, Salvage therapy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Lung cancer, Adverse effect, MNSCLC, Chemotherapy, Auto-antibodie, PD-1/PDL-1-blockade, business.industry, Hazard ratio, Cancer, Articles, medicine.disease, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Nivolumab, business

الوصف: Immune-checkpoint blockade by Nivolumab, a human monoclonal antibody to programmed cell death receptor-1, is an emerging treatment for metastatic non-small cell lung cancer (mNSCLC). In order to prolong patient survival, this treatment requires a continuous cross-priming of tumor derived-antigens to supply fresh tumor-specific immune-effectors; a phenomenon that may also trigger auto-immune-related adverse events (irAEs). The present study therefore investigated the prognostic value of multiple autoimmunity- associated parameters in patients with mNSCLC who were undergoing Nivolumab treatment. This retrospective study included 92 mNSCLC patients who received salvage therapy with Nivolumab (3 mg/kg, biweekly) between September 2015 and June 2018. Log-rank test, Mantel-Cox and McPherson analyses were conducted to correlate patient progression-free survival (PFS) and overall survival (OS) with different parameters including blood cell counts, serum inflammatory markers and auto-antibodies (AAbs). A median PFS and OS of 10 [inter-quartile range (IQR): 5.8-14.2] and 16 [IQR: 6.2-25.8] months, respectively, were recorded, which did not correlated with age, histology or the number of previous chemotherapy lines. Male gender, the type of therapeutic regimens received prior to Nivolumab, and the occurrence of irAEs were revealed to be positive predictors of prolonged survival (P1AAbs among anti-nuclear antigens (ANAs), extractable nuclear antigens (ENAs) and anti-smooth cell antigens (ASMAs) correlated with prolonged PFS [hazard ratio (HR)=0.23; 95% confidence interval (CI): 0.08-0.62; P=0.004] and OS [HR=0.28 (95% CI: 0.09-0.88), P=0.03], with the type of treatment received prior to nivolumab (P=0.007) and with the risk of irAEs (P=0.002). In conclusion, increased serum levels of ANA, ENA and/or ASMA are consequential to Nivolumab administration and are predictive of a positive outcome in mNSCLC patients.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2ea65fae89e1e2a8e0f0281ab68e9397Test
http://hdl.handle.net/10447/512790Test

المؤلفون: Giuseppa Romeo, Rita Agostino, Daniele Caracciolo, Natale Imbesi, Pierfrancesco Tassone, Amalia Luce, Luigi Pirtoli, Alois Nečas, Pierpaolo Correale, Rocco Giannicola, Teresa Del Giudice, Nicoletta Staropoli, Evzen Amler, Pierosandro Tagliaferri, Vito Barbieri, Alessandra Strangio, Pierpaolo Pastina, Rita Emilena Saladino, M. Altomonte, Valerio Nardone, Diana Giannarelli, Paolo Tini, Valentina Arcati, Antonio Giordano, Antonia Consuelo Falzea, Michele Caraglia

المساهمون: Correale, P., Saladino, R. E., Giannarelli, D., Giannicola, R., Agostino, R., Staropoli, N., Strangio, A., Del Giudice, T., Nardone, V., Altomonte, M., Pastina, P., Tini, P., Falzea, A. C., Imbesi, N., Arcati, V., Romeo, G., Caracciolo, D., Luce, A., Caraglia, M., Giordano, A., Pirtoli, L., Necas, A., Amler, E., Barbieri, V., Tassone, P., Tagliaferri, P.

المصدر: Journal for ImmunoTherapy of Cancer, Vol 8, Iss 1 (2020)
Journal for Immunotherapy of Cancer

مصطلحات موضوعية: Male, Cancer Research, Lung Neoplasms, medicine.medical_treatment, Immunology, Human leukocyte antigen, Cancer immunotherapy, HLA Antigens, Carcinoma, Non-Small-Cell Lung, Immunotherapy Biomarkers, medicine, Humans, Immunology and Allergy, Cytotoxic T cell, Lung cancer, Immune Checkpoint Inhibitors, Alleles, Germ-Line Mutation, RC254-282, Aged, Retrospective Studies, Pharmacology, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Survival Analysis, lung neoplasm, Immune checkpoint, HLA-A, antigen presentation, Treatment Outcome, Oncology, tumor biomarkers, B7-H1 antigen, Cancer research, Molecular Medicine, Female, Nivolumab, business, B7-H1 Antigen

الوصف: BackgroundNivolumab is a human monoclonal antibody against programmed cell death receptor-1 (PD-1) able to rescue quiescent tumor infiltrating cytotoxic T lymphocytes (CTLs) restoring their ability to kill target cells expressing specific tumor antigen-derived epitope peptides bound to homologue human leukocyte antigen (HLA) molecules. Nivolumab is currently an active but expensive therapeutic agent for metastatic non-small cell lung cancer (mNSCLC), producing, in some cases, immune-related adverse events (irAEs). At the present, no reliable biomarkers have been validated to predict either treatment response or adverse events in treated patients.MethodsWe performed a retrospective multi-institutional analysis including 119 patients with mNSCLC who received PD-1 blockade since November 2015 to investigate the predictive role of germinal class I HLA and DRB1 genotype. We investigated the correlation among patients’ outcome and irAEs frequency with specific HLA A, B, C and DRB1 alleles by reverse sequence-specific oligonucleotide (SSO) DNA typing.ResultsA poor outcome in patients negative for the expression of two most frequent HLA-A alleles was detected (HLA: HLA-A*01 and or A*02; progression-free survival (PFS): 7.5 (2.8 to 12.2) vs 15.9 (0 to 39.2) months, p=0.01). In particular, HLA-A*01-positive patients showed a prolonged PFS of 22.6 (10.2 to 35.0) and overall survival (OS) of 30.8 (7.7 to 53.9) months, respectively. We also reported that HLA-A and DRB1 locus heterozygosis (het) were correlated to a worse OS if we considered het in the locus A; in reverse, long survival was correlated to het in DRB1.ConclusionsThis study demonstrate that class I and II HLA allele characterization to define tumor immunogenicity has relevant implications in predicting nivolumab efficacy in mNSCLC and provide the rationale for further prospective trials of cancer immunotherapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a1905deaf39a4611f9d4981936aae8b4Test
https://doi.org/10.1136/jitc-2020-000733Test