9 research outputs found
TRAP1 favor glycolytic metabolism and resistance to EGFR inhibitors in human colorectal carcinoma through regulation of PFK.
No full textTRAP1 enhances Warburg metabolism through modulation of PFK1 expression/activity and favors resistance to EGFR inhibitors in human colorectal carcinomas
No full textMetabolic rewiring is a mechanism of adaptation to unfavorable environmental conditions and tumor progression. TRAP1 is an HSP90 molecular chaperone upregulated in human colorectal carcinomas (CRCs) and responsible for downregulation of oxidative phosphorylation (OXPHOS) and adaptation to metabolic stress. The mechanism by which TRAP1 regulates glycolytic metabolism and the relevance of this regulation in resistance to EGFR inhibitors were investigated in patient-derived CRC spheres, human CRC cells, samples, and patients. A linear correlation was observed between TRAP1 levels and 18F-fluoro-2-deoxy-glucose (18F-FDG) uptake upon PET scan or GLUT1 expression in human CRCs. Consistently, TRAP1 enhances GLUT1 expression, glucose uptake, and lactate production and downregulates OXPHOS in CRC patient-derived spheroids and cell lines. Mechanistically, TRAP1 maximizes lactate production to balance low OXPHOS through the regulation of the glycolytic enzyme phosphofructokinase-1 (PFK1); this depends on the interaction between TRAP1 and PFK1, which favors PFK1 glycolytic activity and prevents its ubiquitination/degradation. By contrast, TRAP1/PFK1 interaction is lost in conditions of enhanced OXPHOS, which results in loss of TRAP1 regulation of PFK1 activity and lactate production. Notably, TRAP1 regulation of glycolysis is involved in resistance of RAS-wild-type CRCs to EGFR monoclonals. Indeed, either TRAP1 upregulation or high glycolytic metabolism impairs cetuximab activity in vitro, whereas TRAP1 targeting and/or inhibition of glycolytic pathway enhances cell response to cetuximab. Finally, a linear correlation between 18F-FDG PET uptake and poor response to cetuximab in first-line therapy in human metastatic CRCs was observed. These results suggest that TRAP1 is a key determinant of CRC metabolic rewiring and favors resistance to EGFR inhibitors through regulation of glycolytic metabolism
Gene copy number and post-transductional mechanisms regulate TRAP1 expression in human colorectal carcinomas
No full textTumor Necrosis Factor Receptor-Associated Protein 1 (TRAP1) is a heat shock protein 90 (HSP90) molecular chaperone overexpressed in 60–70% human colorectal carcinomas (CRCs) and the co-upregulation of TRAP1 and associated 6-related proteins identifies metastatic CRCs with poor prognosis. Since the molecular mechanisms responsible for TRAP1 regulation are still unknown, the significance of TRAP1 gene copy number (CN) and the role of post-transductional protein modifications were addressed. TRAP1 gene aneuploidy accounted for 34.5% of cases in a cohort of 58 human CRCs and TRAP1 CN correlated with its mRNA and protein expression, suggesting that transcriptional mechanisms are responsible for TRAP1 upregulation. Furthermore, the analysis of the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium/The Cancer Genome Atlas (CPTAC/TCGA) CRC database showed that TRAP1 polysomy significantly correlates with lymph node involvement. However, a subgroup of tumors showed TRAP1 protein levels independent from its CN. Of note, a direct correlation was observed between TRAP1 protein levels and the expression of S-nitrosoglutathione reductase (GSNOR), a denitrosylase involved in the regulation of protein S-nitrosylation. Furthermore, CRC cell lines exposed to hypoxia or dichloroacetate treatment showed the downregulation of TRAP1 upon GSNOR silencing and this resulted in increased TRAP1 mono/polyubiquitination. These data suggest that transcriptional and post-transductional mechanisms account for TRAP1 expression in human CRCs and GSNOR protects TRAP1 from S-nitrosylation and consequent proteasome degradation mostly in conditions of stress
TRAP1 favors glycolytic metabolism and resistance to EGFR inhibitors in human colorectal carcinoma through regulation of PFK.
No full textTRAP1 controls cell cycle progression through the regulation of CDK1 and MAD2 expression/ubiquitination in human breast, colon and lung carcinomas.
No full textElectrophysiologic effects of oral encainide in A-V nodal reentrant tachycardia (slow-fast type).
No full textCorrection to: Safety and efficacy of COVID-19 vaccines in patients on dialysis: a multicentre cohort study in Italy
No full textThe COVIDVaxDia Study Group in html which currently reads Francesca Menniti-Ippolito, Roberto Da Cas, Flavia Chiarotti, Massimo Fabiani, Giuseppe Traversa, Piergiorgio Messa, Alfonso Mele, Salvatore De Masi, Francesca Colavita, Concetta Castilletti, Carmine Zoccali, Aldo Pietro Maggioni, Andrea Lorimer, Martina Ceseri, Ester Baldini, Francesca Bianchini, Laura Sarti, Giovanni Baglio, Andrea Mariano and Eva Alessi. It should read as: Francesca Menniti-Ippolito, Roberto Da Cas, Flavia Chiarotti, Massimo Fabiani, Giuseppe Traversa, Piergiorgio Messa, Alfonso Mele, Salvatore De Masi, Francesca Colavita, Concetta Castilletti, Carmine Zoccali, Aldo Pietro Maggioni, Andrea Lorimer, Martina Ceseri, Ester Baldini, Francesca Bianchini, Laura Sarti, Giovanni Baglio, Andrea Mariano & Eva Alessi, Lorenzo Di Liberato, Luigi Amoroso, Nicola Spetrino, Milva Di Giovanni, Carlo Sapio, Irma Figlia, Roberto Pititto, Teresa Papalia, Rosita Greco, Francesca Leone, Francesco Maria D’Agostino, Mariangela Campolo, Maria Rosa La Gamba, Francesca Mallamaci, Vincenzo Panuccio, Giovanna Parlongo, Giuseppe Natale, Domenico Tramontana, Ivania Maria Figliano, Santo Vitiello, Anna Maria Frangiosa, Domenico Caserta, Pasqualina Acconcia, Nunzia Paudice, Alfonso De Maio, Salvatore Cascone, Marilina Siani, Mario Cioffi, Nataliya Romanyuk, Franca Pagnano, Antonio De Donato, Ersilia Satta, Alessandra Perna, Francesco Trepiccione, Alessandro Cerrone, Gianluca Garofalo, Giancarlo Marinelli, Roberta D’Amato, Enrico De Felice, Alfredo Vacca, Salvatore Coppola, Vincenzo Cuomo, Maria Palma Iavarone, Annalisa Ciotola, Vincenzo Puglia, Pio Granato, Carla Lamberti, Giorgio Capasso, Domenico Bonanno, Marco Ventre, Veronica Amendola, Fabio Cappabianca, Elena Mancini, Davide Ricci, Daniela Cecilia Cannarile, Roberta Benevento, Bianca Perciaccante, Alda Storari, Yuri Battaglia, Giovanni Piva, Giovanni Mosconi, Alessandra Spazzoli, Paolo Ferdinando Bruno, Katia Ambri, Barbara Veterani, Sara Signorotti, Marcora Mandreoli, Renato Mario Rapanà, Maria Teresa Benedetto, Laura Patregnani, Maddalena Zambelli, Gaetano Alfano, Mariacristina Gregorini, Silvia Mattei, Francesca Iannuzzella, Elena Pelizzaro, Luca Camparini, Giuseppe Battaglino, Dino Romanini, Antonio Irlando, Lojze Celik, Giuseppa Natale, Maria Cristina Torre, Ilaria Umbro, Nicola Pirozzi, Loredana Fazzari, Lucia Pantano, Antonio Paone, Marco Galliani, Veronica Baglio, Eleonora Moscaritolo, Sabrina Fierimonte, Maria De Cristofaro, Elena Nebuloso, Paolo Menè, Francesca Romana Festuccia, Giulia Talarico, Claudia Fofi, Maria Elena Bracaccia, Ernesto Anselmo Cioffi, Fabio Mazza, Pasquale Polito, David Micarelli, Roberto Addesse, Lida Tartaglione, Sandro Feriozzi, Francesca Romana Della Rovere, Natalia Chipilova, Micol Manzuoli, Paolo Sacco, Francesca Ansaldo, Chiara Bottaro, Sonia Marre, Francesc Viazzi, Valeria Falqui, Novella Conti, Angelica Parodi, Valentina Zanetti, Francesca Cappadona, Andrea Speciale, Giancarlo Mancuso, Monica Repetto, Emanuela Chiara Vigo, Cairo Montenotte, Anna Maria Murgia, Piero Ruggenenti, Patrizia Ondei, Carmela Giuseppina Condemi, Sivia Bernardi, Francesco Scolari, Paola Gaggia, Federico Alberico, Chiara Manenti, Brunella Valzorio, Corrado Camerini, Agnese Gallico, Michela Tonoli, Federico Daffara, Roberto Zubbani, Simona Guerini, Mattia Zappa, Nicole Zambetti, Alessandra Dalla Gassa, Paola Baldan, Luca Fraizzoli, Sergio Bisegna, Nicola Palmieri, Marco Petrilli, Giusy Mandanici, Francesca Serena Stefani, Valeria Ogliari, Cristina Tantardini, Fabio Malberti, Paola Pecchini, Vincenzo La Milia, Carlo Maria Guastoni, Annalisa Neri, Marina Cornacchiari, Marco Farina, Francesco Barbisoni, Milena Maggio, Mario Cozzolino, Matthias Cassia, Michela Frittoli, Lorenza Magagnoli, Rossella De Leonardis, Roberta Casazza, Simone Vettoretti, Emanuele Grimaldi, Matteo Abinti, Francesca Maria Ida Carminati, Silvia Giuliani, Matteo Benedetti, Nicholas Delfrate, Elisa Colombo, Angela Cervesato, Enrico Eugenio Minetti, Alberto Montoli, Chiara Brunati, Valerae Li Bergolis, Maurizio Galllieni, Cristina Airaghi, Monique Buskermolen, Laura Cosmai, Maria Antonietta Orani, Cristina De Salvo, Giuseppe Vezzoli, Giorgio Slaviero, Chiara Lanzani, Federico Pieruzzi, Gina Contaldo, Barbara Trezzi, Teresa Rampino, Fabrizio Grosjean, Paola Borille, Ciro Esposito, Giuseppe Sileno, Marta Arazzi, Gianvincenzo Melfa, Mariagiulia Tettamanti, Anna Tosetti, Marco D’Amico, Maria Giulia Magatti, Silvia Peiti, Luciano Pedrini, Annalisa Feliciani, Elena Pezzini, Silvio Volmer Bertoli, Daniele Ciurlino, Silvia Tedoldi, Vania Prettico, Giulia Maria Magni, Antonietta Gazo, Maurizio Nai, Silvia Muciaccia, Graziana Battini, Lino Merlino, Paola Casanova, Federica Lencia, Maddalena Ricci, Andrea Ranghino, Mauro Valente, Carolina Finale, Eleonora Guerrini, Marta Canonici, Stefano Santarelli, Rosa Maria Agostinelli, Marina Di Luca, Mauro Martello, Cristina Silvestri, Veronica Bertuzzi, Assunta Cardillo, Valentina Nastasi, Sara Belcastro, Marco Manganaro, Emanuele Luigi Parodi, Valentina Vaccaro, Antonella Giolito, Stefano Cusinato, Michele Battista, Elena Ragazzoni, Paola Marcella Carpani, Emanuele Stramignoni, Silvana Savoldi, Guido Martina, Chiara Deagostini, Marica Magnetti, Stefania Bussolino, Federica Ventrella, Sonia Santi, Marita Marengo, Daniela Falconi, Ilaria Serra, Luca Besso, Davide Diena, Doriana Chiari Notti, Paola David, Luciana Gravellone, Corrado Vitale, Silvia Berutti, Silvia Ganci, Federica Neve Vigotti, Giulio Cesano, Maurizio Borzumati, Patrizia Bio, Stefania Gioira, Oliviero Filiberti, fabiola Pagani, Simonetta Ottone, Carlo Lomonte, Vincenzo Montinaro, Vito Pepe, Elisabetta Manno, Salvatore Di Paolo, Luigi Natalicchio, Carmela Gallo, Francesca pansini, Rossella Varvara, Filomena D’Elia, NIcola Coviello, Concetta Prisciandaro, Lucia Vernò, Fernanda Misceo, Pierfelice Zazzera, Antonella Matrella, Loreto Gesualdo, Anna Maria Di Palma, Virginia Pronzo, Federica Cassone, Salvatore Di Paolo, Tiziana Piccolo, Dora Porcelluzzi, Antonella Di Franco, Mario Giannetto, Chiara Villani, Luigi Vernaglione, Angelo Specchio, Laura Stoico, Giovanni Stallone, Vincenzo Losappio, Barbara Infante, Luigi Morrone, Anna Lisa Marangi, Angela Rodio, Christian D’Altri, Paolo Venerito, Francesca Cianciotta, Filippo Aucella, Gaetano Ferrara, Anna Rachele Nardella, Luigi Francesco Pio Morrone, Maria Grazia Corallo, Giuseppina D’Ettorre, Francesco Caccetta, Davide Gianfreda, Antonello Pani, Gianfranca Cabiddu, Stefania Caria, Maria Maddalena Romano, Ciro Adamo, Giovanni Giorgio Battaglia, Barbara Pocorobba, Emanuela Prencipe, Margherita Saraceno, Luana Scuderi, Salvatore Randone, Francesca Bruno, Rossella Rita Marchese, Antonio Granata, Daniela Puliatti, Carmelita Marcantoni, Luca Zanoli, Ambra D’anca, Domenico Santoro, Guido Gembillo, Alfio Eduardo Giuffrida, Vincenzo Labbozzetta, Angelo Tralongo, Gioacchino Li Cavoli, Carmela Zaggarigo, Paolo Conti, Sofia Giovannini, Silvia Farsetti, Pietro Claudio Giovanni Dattolo, Aris Tsalouchos, Stefano Michelassi, Marco Gallo, Irene Bandor, Nadia Sami, Daniela Riccomi, Lorena Traversari, Maria Grazia Tabbi, Maria Luisa Bonincontro, Vera Bonell, Giuliano Brunori, Diana Zarantonello, Alessandro Laudon, Antonio Selvi, Stefania Santoni, Davide Massimiani, Davide Rossi, Lorenzo Calò, Barbara Rossi, Giuseppe Scaparrotta, Fulvio Fiorini, Valentina Iacono, Carlo Rugiu, Monica Slaviero, Maurizio Nordio, Riccarda Maria Puggia, Adriana Caberlotto, Flavio Scanferla, Vincenzo Casoria, Federica Gramegna, Gina Meneghel, Ilenia Filippi, Anna Giacomini, Claudio Ronco, Anna Giuliani, Sabrina Milan Manani, Monica Zanella
Safety and efficacy of COVID-19 vaccines in patients on dialysis: a multicentre cohort study in Italy
No full textBackground: The aim of this study was to evaluate the efficacy and safety of COVID-19 vaccines in patients undergoing haemodialysis in Italy compared to the general population. Methods: In this cohort study, 118 dialysis centres from 18 Italian Regions participated. Individuals older than 16 years on dialysis treatment for at least 3 months, who provided informed consent were included. We collected demographic and clinical information, as well as data on vaccination status, hospitalisations, access to intensive care units and adverse events. We calculated the incidence, hospitalisation, mortality, and fatality rates in the vaccinated dialysis cohort, adjusted for several covariates. The incidence rates of infection in the dialysis cohort and the general population were compared through Standardised Incidence Rate Ratio. Results: The study included 6555 patients vaccinated against SARS-CoV-2 infection according to the schedule recommended in Italy. Between March 2021 and May 2022, there were 1096 cases of SARS-CoV-2 infection, with an incidence rate after completion of the three-dose vaccination cycle of 37.7 cases per 100 person-years. Compared to the general population, we observed a 14% reduction in the risk of infection for patients who received three vaccine doses (Standardised Incidence Rate Ratio: 0.86; 95% Confidence Interval: 0.81–0.91), whereas no statistically significant differences were found for COVID-19-related hospitalisations, intensive care unit admissions or death. No safety signals emerged from the reported adverse events. Conclusions: The vaccination program against SARS-CoV-2 in the haemodialysis population showed an effectiveness and safety profile comparable to that seen in the general population. Graphical abstract: [Figure not available: see fulltext.
ЭКСПРЕССИЯ МАРКЕРОВ CD44 И CD24 В БИОПСИЙНОМ МАТЕРИАЛЕ БОЛЬНЫХ ТРОЙНЫМ НЕГАТИВНЫМ РАКОМ МОЛОЧНОЙ ЖЕЛЕЗЫ ДО ЛЕЧЕНИЯ
No full textThe role of the expression of CD44 and CD24 in breast cancer (BC) has been explored in many laboratories around the world to identify predictive markers of tumor aggressiveness and patient’s response to anticancer therapy. These proteins participate in the process of tumor growth, metastasis and formation of cancer stem cells (CSCs). The study of CD44 and CD24 expression in triple negative (TN) BC, which is the most aggressive breast cancer subtype, is of particular interest. The aim of this study was to determine the relationship between the expression of CD44 and CD24 markers in biopsy samples of TNBC patients before treatment and clinical/ morphological characteristics of the tumors. Material and Methods. The study group included 67 patients with stage I–IV TNBC. Flow cytometry was used to determine the proportion of cells with CSC immunophenotype (CD44+/CD24-/low) in biopsy samples from the primary tumor of 65 patients and lymph nodes of 6 patients. In addition, the proportion of cells with all possible combinations of expression of these surface proteins was estimated. Results. Cells with CSC immunophenotype were detected in all patients with a wide individual variability of CSC proportion from 0.4 % to 77.0 % (median – 10.9 %). There were no differences in the proportion of CSCs in the primary tumor and lymph nodes. No statistically significant correlation between the proportion of CSCs in the primary tumor and the clinical/morphological parameters, including tumor size and differentiation grade, evidence of regional or distant metastases, tumor, size of the fraction of proliferating cells estimated by Ki67 expression, was found in either single or multivariate analysis. There was also no association of the above parameters (except Ki67) with immunophenotypes. A high proportion of Ki67-positive cells in the primary tumor was associated with the CD44-CD24-phenotype. Conclusion. The expression of CD44 and CD24 in biopsy samples of TNBC before treatment did not correlate with the clinical and morphological characteristics of the tumors, excepting Ki67 expression.Индивидуальные особенности экспрессии CD44 и CD24 при раке молочной железы (РМЖ) изучаются во многих лабораториях мира в рамках поиска прогностических маркеров агрессивности опухолевого процесса и эффективности противоопухолевой терапии, что во многом обусловлено участием этих белков в процессах опухолевого роста, метастазирования и формирования популяции опухолевых стволовых клеток (ОСК), которые составляют наиболее резистентную часть злокачественных новообразований к радиационным и многим химиотерапевтическим воздействиям. Особый интерес представляет исследование экспрессии CD44 и CD24 в случае тройного негативного (ТН) РМЖ – наиболее агрессивного среди различных молекулярных подтипов злокачественных новообразований данной локализации. Цель исследования – выяснение возможной взаимосвязи экспрессии маркеров CD44 и CD24 в биопсийном материале больных ТН РМЖ до лечения с клинико-морфологическими характеристиками опухоли. Материал и методы. В исследование включено 67 больных ТН РМЖ I–IV стадии. С помощью проточной цитометрии в биоптатах из первичного опухолевого очага 65 больных и лимфоузлов 6 больных определяли долю клеток с иммунофенотипом ОСК, которые характеризуются наличием на клеточной мембране CD44 при низкой экспрессии CD24 или отсутствии таковой (CD44+/ CD24-/low). Кроме того, оценивали долю клеток со всеми возможными комбинациями экспрессии этих поверхностных белков. Результаты. Клетки с иммунофенотипом ОСК выявлены в первичном очаге всех больных при широкой индивидуальной вариабельности их доли – от 0,4 до 77,0 % (медиана – 10,9 %). Не обнаружено различий доли ОСК в первичном очаге и в лимфоузлах. Ни при одно-, ни при многофакторном анализе не установлено значимой корреляции доли ОСК ни с одним из клинико-морфологических показателей, включая размер и степень дифференцировки опухоли, наличие регионарных и отдаленных метастазов, размер фракции пролиферирующих клеток, оцениваемый по экспрессии Ki67. Также не установлено ассоциации указанных показателей (кроме Ki67) ни с одним из преобладающих в исследованном материале иммунофенотипов. В первичном опухолевом очаге высокая доля Ki67-позитивных клеток была ассоциирована с фенотипом CD44-CD24-. Заключение. Экспрессия маркеров CD44 и CD24 в клетках биопсийного материала больных ТН РМЖ до лечения не коррелирует с клинико-морфологическими характеристиками опухоли, кроме экспрессии Ki67
