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1. Assessing the safety and activity of cabozantinib combined with lanreotide in gastroenteropancreatic and thoracic neuroendocrine tumors: rationale and protocol of the phase II LOLA trial

Author

Corti, Francesca, Brizzi, Maria Pia, Amoroso, Vito, Giuffrida, Dario, Panzuto, Francesco, Campana, Davide, Prinzi, Natalie, Milione, Massimo, Cascella, Tommaso, Spreafico, Carlo, Randon, Giovanni, Oldani, Simone, Leporati, Rita, Scotto, Giulia, Pulice, Iolanda, Stocchetti, Benedetta Lombardi, Porcu, Luca, Coppa, Jorgelina, Di Bartolomeo, Maria, de Braud, Filippo, and Pusceddu, Sara

Published
2023
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2. Preclinical in vivo antitumor activity experiments : methodological pitfalls and a new framework for their design and analysis

Author

Porcu, Luca

Subjects
616.99
Abstract

Aims: Poorly designed, analyzed and reported preclinical in vivo experiments (inVivoExp) raise ethical as well as scientific concerns. It could be hypothesized that the recurring failure of apparently promising interventions to improve outcome in clinical trials has been partially caused by poor quality of statistical design and analysis (QoStat) of inVivoExp. This project aimed to assess and correlate QoStat with clinical activity, and to improve the statistical framework used in inVivoExp. Methods: A systematic search of Medline and EMBASE databases was carried out to identify epithelial ovarian cancer clinical trials assessing the antitumor activity of candidate compounds (CC) as monotherapy. For each eligible CC, a systematic search was carried out to identify scientific papers reporting inVivoExp on rats and mice, in which the CC was administered as monotherapy. An ad hoc checklist was used to assess QoStat of inVivoExp. QoStat was correlated to the clinical activity. Results: Fifty-two eligible CCs and 121 inVivoExp were identified. In 45 out of 120 (37.5%) inVivoExp the method of treatment assignment was not specified. The randomization type was specified in 3 out of 74 (4.1%) inVivoExp and sample size was justified in 9 (7.4%) inVivoExp. If the primary outcome was tumor volume, the antitumor activity endpoint was declared in 14 out of 106 (13.2%) inVivoExp. The length of follow-up was specified in 43 (35.5%) inVivoExp. Outcome assessor was blinded in 5 (4.1%) inVivoExp. Inefficient statistical methods were often applied to analyze tumor growth data. A new statistical framework based on the Mann-Whitney statistic was proposed and applied to a specific tumor model. Conclusions: QoStat of inVivoExp was so poor that the correlation with clinical activity was impossible. The magnitude of the biological signal was poorly estimated. The new statistical framework should be considered for the design and analysis of in vivo tumor growth studies.

Published
2020
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3. Guideline Application in Real world: multi-Institutional Based survey of Adjuvant and first-Line pancreatic Ductal adenocarcinoma treatment in Italy. Primary analysis of the GARIBALDI survey

Author

Reni, Michele, Macchini, Marina, Orsi, Giulia, Peretti, Umberto, Valente, Mariamaddalena, Giommoni, Elisa, Antonuzzo, Lorenzo, Di Costanzo, Francesco, Bergamo, Francesca, Zagonel, Vittorina, Lonardi, Sara, Buggin, Federica, Milella, Michele, Palmerio, Silvia, Cavanna, Luigi, Di Nunzio, Camilla, Di Marco, Maria Cristina, Grassi, Elisa, Spada, Massimiliano, Messina, Marco, Cordio, Stefano, Avola, Francesco, Aprile, Giuseppe, Pagano, Salvatore, Simionato, Francesca, Cardellino, Giovanni Gerardo, Majer, Federica, Maiello, Evaristo, Latiano, Tiziana Pia, Chiarazzo, Cinzia, Artioli, Fabrizio, Razzini, Giorgia, Pasqualini, Antonella, Ghidini, Michele, Binda, Elisa, Lazzarelli, Silvia, Bozzarelli, Silvia, Sala, Simona, Luppi, Gabriele, Pettorelli, Elisa, Spallanzani, Andrea, Vicario, Giovanni, Salmaso, Flavia, Basso, Marco, Silvestris, Nicola, Del Curatolo, Sabina, Zustovich, Fable, Bongiovanni, Francesca, Longobardi, Ciro, Sandi, Ilenia, Fontanella, Caterina, Montelatici, Silvia, Giordano, Monica, Luchena, Giovanna, Gilardoni, Micol, Tamburini, Emiliano, Rudnas, Britt, Venturini, Barbara, Merelli, Barbara, Negrini, Giorgia, Vici, Elio Maria, Marabese, Alessandra, Garetto, Cristina, Curcio, Paola, Cinieri, Saverio, Cinefra, Margherita, Ferrara, Pasqualinda, Cantore, Maurizio, Morselli, Patrizia, Fumi, Guglielmo, Isidori, Agnese, Ciccarese, Giovanni, Paolo Frassineti, Giovanni Luca, Pagan, Flavia, Vaccaro, Vanja, Spoto, Chiara, Ferrara, Marianna, Garufi, Carlo, Caporale, Marta, Vasile, Enrico, Salani, Francesca, Barone, Elisa, Berardi, Rossana, Onofri, Azzurra, Ballatore, Zelmira, Lucarelli, Alessandra, Barucca, Alessandra, Pancotti, Amedeo, Scipioni, Teresa, Bencardino, Katia, Marrapese, Giovanna, Idotta, Laura, Petrelli, Fausto, Lonati, Veronica, Ceribelli, Anna, Giuli, Angelo, Zannori, Cristina, Bassanelli, Maria, Mambrini, Andrea, Ginocchi, Laura, Orlandi, Massimo, Celio, Luigi, Niger, Monica, Biamonte, Lavinia, Tamberi, Stefano, Piancastelli, Alessandra, Papiani, Giorgio, Valli, Irene, Allione, Paolo, Boe, Maria Giovanna, Scartozzi, Mario, Lai, Eleonora, Pireddu, Annagrazia, Ziranu, Pina, Demurtas, Laura, Puzzoni, Marco, Mariani, Stefano, Pretta, Andrea, Liscia, Nicole, Savastano, Clementina, Malaspina, Valentina, Tonini, Giuseppe, Grassani, Teresa, Barco, Barbara, Pierosandro, Tagliaferri, Ciliberto, Domenico, Ierardi, Antonella, Calandruccio, Natale Daniele, Minotti, Vincenzo, Matocci, Roberta, Torri, Valter, Porcu, Luca, Rulli, Erica, De Simone, Irene, Carlucci, Luciano, Rulli, Eliana, Poli, Davide, Tonto, Paola, Scellato, Francesca, Pinto, Carmine, Reni, M., Giommoni, E., Bergamo, F., Milella, M., Cavanna, L., Di Marco, M.C., Spada, M., Cordio, S., Aprile, G., Cardellino, G.G., Maiello, E., Bernardini, I., Ghidini, M., Bozzarelli, S., Macchini, M., Orsi, G., De Simone, I., Rulli, Er., Porcu, L., Torri, V., and Pinto, C.

Published
2023
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4. Evaluation of Major Pathologic Response and Pathologic Complete Response as Surrogate End Points for Survival in Randomized Controlled Trials of Neoadjuvant Immune Checkpoint Blockade in Resectable in NSCLC

Author

Hines, Jacobi B., primary, Cameron, Robert B., additional, Esposito, Alessandra, additional, Kim, Leeseul, additional, Porcu, Luca, additional, Nuccio, Antonio, additional, Viscardi, Giuseppe, additional, Ferrara, Roberto, additional, Veronesi, Giulia, additional, Forde, Patrick M., additional, Taube, Janis, additional, Vokes, Everett, additional, Bestvina, Christine M., additional, Dolezal, James M., additional, Sacco, Matteo, additional, Monteforte, Marta, additional, Cascone, Tina, additional, Garassino, Marina C., additional, and Torri, Valter, additional

Published
2024
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5. From Tumor Macroenvironment to Tumor Microenvironment: The Prognostic Role of the Immune System in Oral and Lung Squamous Cell Carcinoma.

Author

Battista, Rosa Alessia, Pini, Giacomo Maria, Finco, Alex, Corso, Filippo, Galli, Andrea, Arrigoni, Gianluigi, Doglioni, Claudio, Callea, Marcella, Paccagnella, Matteo, Porcu, Luca, Filipello, Federica, Mazzola, Marco, Foggetti, Giorgia, Gregorc, Vanesa, Giordano, Leone, Bussi, Mario, Mirabile, Aurora, and Veronesi, Giulia

Subjects
ANTIGEN analysis, SQUAMOUS cell carcinoma, NEUTROPHIL lymphocyte ratio, REFERENCE values, INFLAMMATORY mediators, RESEARCH funding, IMMUNE system, LYMPHOCYTES, RETROSPECTIVE studies, TREATMENT effectiveness, PLATELET lymphocyte ratio, ANTIGENS, MONOCYTE lymphocyte ratio, LUNG tumors, TUMOR classification, PROGRESSION-free survival, COMORBIDITY, OVERALL survival, EVALUATION
Abstract

Simple Summary: This study explores the involvement of the immune system in oral and lung squamous cell carcinoma. Given the increasing recognition of the immune system's significance in cancer, the study analyzes key components of both tumor macroenvironment and microenvironment. In detail, the focus is on systemic inflammation markers, such as Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Monocyte-to-Lymphocyte Ratio (MLR). Additionally, this study investigates Tumor-Infiltrating Lymphocytes (TILs) and CD8+ cells in the tumor microenvironment. We aimed to better understand the impact of these prognostic factors on overall survival (OS) and disease-free survival (DSF) in order to enhance cancer risk stratification and guide therapeutic decisions. Background: The interplay between cancer cells and the immune system is crucial in cancer progression and treatment. In this regard, the tumor immune microenvironment and macroenvironment, marked by systemic inflammation markers and TILs, could be considered key prognostic factors in tumors, including oral and lung squamous cell carcinoma. Methods: We conducted a retrospective clinical study on patients with Oral Squamous Cell Carcinoma (OSCC) and Lung Squamous Cell Carcinoma (LUSCC), examining stages, comorbidities, treatments, and outcomes. We evaluated the prognostic significance of pre-surgical systemic inflammation markers and tumor microenvironment composition. Results: Associations were found between systemic inflammation markers—NLR, MLR, and PLR—and tumor microenvironment factors, such as TILs and CD8+ cell prevalence—elevated inflammation markers correlated with advanced stages. Specifically, NLR was prognostic in OSCC, whereas PLR was prognostic in LUSCC. Using a cutoff value, we divided our tumor samples into two prognostic groups. Moreover, TILs levels >15% of tumor stroma correlated with prolonged overall survival in both OSCC and LUSCC, while increased CD8+ expression was linked to extended disease-free survival in LUSCC. Discussion: Systemic inflammation markers and TILs can be valuable prognostic factors of survival, highlighting the immune response's role in OSCC and LUSCC. Despite limited clinical integration of the presented cohorts due to a lack of standardization, we concluded that analyzing tumor immune profiles may offer novel prognostic insights. Conclusions: Future integration into cancer classification could improve risk stratification and treatment guidance. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Long-term safety and efficacy of left atrial appendage occlusion in dialysis patients with atrial fibrillation: a multi-center, prospective, open label, observational study

Author

Genovesi, Simonetta, primary, Porcu, Luca, additional, Rebora, Paola, additional, Slaviero, Giorgio, additional, Casu, Gavino, additional, Bertoli, Silvio, additional, Airoldi, Flavio, additional, Buskermolen, Monique, additional, Gallieni, Maurizio, additional, Pieruzzi, Federico, additional, Rovaris, Giovanni, additional, Montoli, Alberto, additional, Piccaluga, Emanuela, additional, Molon, Giulio, additional, Alberici, Federico, additional, Adamo, Marianna, additional, Gaspardone, Achille, additional, D'Angelo, Giuseppe, additional, Merella, Pierluigi, additional, Vezzoli, Giuseppe, additional, Trezzi, Barbara, additional, and Mazzone, Patrizio, additional

Published
2023
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11. A Ten-Year Real-Life Experience with Pazopanib in Uterine Leyomiosarcoma in Two High-Specialized Centers in Italy: Effectiveness and Safety.

Author

Mantiero, Mara, Bini, Marta, Polignano, Maggie, Porcu, Luca, Sanfilippo, Roberta, Fabbroni, Chiara, Parma, Gabriella, Lapresa, Mariateresa, Calidona, Carmelo, Silvestri, Cecilia, Franza, Andrea, Raspagliesi, Francesco, Colombo, Nicoletta, and Ducceschi, Monika

Subjects
THERAPEUTIC use of antineoplastic agents, LEIOMYOSARCOMA, DRUG efficacy, RESEARCH, HYPERTENSION, HEALTH facilities, DIARRHEA, NAUSEA, UTERINE tumors, RETROSPECTIVE studies, EXPERIENCE, VOMITING, DESCRIPTIVE statistics, DRUG side effects, PATIENT safety, OVERALL survival, DRUG toxicity, EVALUATION
Abstract

Simple Summary: Pazopanib is an oral drug for metastatic pretreated uterine leiomyosarcoma that received approval in 2012, but poor data have been reported on its activity in real life since the disease is very rare. Uterine leiomyosarcoma has a poor objective response rate to other agents. We assessed the effectiveness and safety of pazopanib in everyday clinical practice, showing its activity and tolerability in patients. Background: Uterine leiomyosarcoma (uLMS) is characterized by aggressive behavior associated with a high risk of relapse and mortality. Several therapeutic agents have been employed in the treatment of metastatic disease, with a poor objective response rate. Pazopanib, approved in 2012, is a multi-targeted, orally active small molecule that exerts its effects by inhibiting several tyrosine kinases. To date, poor research on real-life data has been conducted. We aimed to assess the effectiveness and safety of the drug in everyday clinical practice. Methods: We present results of multicenter retrospective data on 38 patients with heavily pretreated metastatic uLMS who underwent oral pazopanib during their therapeutic journey. Results: At a median follow-up of 8.6 months, the disease control rate was 55.2%, with 17% partial responses and 15 patients (39.5%) with stable disease. At a median follow-up of 8.6 months, median progression-free survival was 4 months, and median overall survival was 19.8 months. The most common grade 3 adverse events (AEs) drug-related were hepatic toxicities, diarrhea, hypertension, nausea, and vomiting (all of them with an incidence of 5% considering the whole study cohort). No grade 4 AEs occurred. Conclusions: Pazopanib in everyday clinical practice is safe and shows a good disease control rate with prolonged survival. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Radiological imaging markers predicting clinical outcome in patients with metastatic colorectal carcinoma treated with regorafenib: post hoc analysis of the CORRECT phase III trial (RadioCORRECT study)

Author

Ricotta, Riccardo, Verrioli, Antonella, Ghezzi, Silvia, Porcu, Luca, Grothey, A., Falcone, Alfredo, Van Cutsem, Eric, Argilés, Guillem, Adenis, Antoine, Ychou, Marc, Barone, Carlo, Bouché, Olivier, Peeters, Marc, Humblet, Yves, Mineur, Laurent, Sobrero, Alberto F., Hubbard, Joleen M., Cremolini, Chiara, Prenen, Hans, Tabernero, Josep, Jarraya, Hajer, Mazard, Thibault, Deguelte-Lardiere, Sophie, Papadimitriou, Konstantinos, Van den Eynde, Marc, Pastorino, Alessandro, Redaelli, Daniela, Bencardino, Katia, Funaioli, Chiara, Amatu, Alessio, Carlo-Stella, Giulia, Torri, Valter, Sartore-Bianchi, Andrea, Vanzulli, Angelo, and Siena, Salvatore

Published
2016
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13. Longitudinal changes of SARA scale in Friedreich ataxia: Strong influence of baseline score and age at onset.

Author

Porcu, Luca, Fichera, Mario, Nanetti, Lorenzo, Rulli, Eliana, Giunti, Paola, Parkinson, Michael H., Durr, Alexandra, Ewenczyk, Claire, Boesch, Sylvia, Nachbauer, Wolfgang, Indelicato, Elisabetta, Klopstock, Thomas, Stendel, Claudia, Rodríguez de Rivera, Francisco Javier, Schöls, Ludger, Fleszar, Zofia, Giordano, Ilaria, Didszun, Claire, Castaldo, Anna, and Rai, Myriam

Subjects
*AGE of onset, *ATAXIA, *DISEASE duration, *DISEASE progression, *STATISTICAL models
Abstract

Background: The Scale for Assessment and Rating of Ataxia (SARA) is widely used in different types of ataxias and has been chosen as the primary outcome measure in the European natural history study for Friedreich ataxia (FA). Methods: To assess distribution and longitudinal changes of SARA scores and its single items, we analyzed SARA scores of 502 patients with typical‐onset FA (<25 years) participating in the 4‐year prospective European FA Consortium for Translational Studies (EFACTS). Pattern of disease progression was determined using linear mixed‐effects regression models. The chosen statistical model was re‐fitted in order to estimate parameters and predict disease progression. Median time‐to‐change and rate of score progression were estimated using the Kaplan–Meier method and weighted linear regression models, respectively. Results: SARA score at study enrollment and age at onset were the major predictive factors of total score progression during the 4‐year follow‐up. To a less extent, age at evaluation also influenced the speed of SARA progression, while disease duration did not improve the prediction of the statistical model. Temporal dynamics of total SARA and items showed a great variability in the speed of score increase during disease progression. Gait item had the highest annual progression rate, with median time for one‐point score increase of 1 to 2 years. Interpretation: Analyses of statistical properties of SARA suggest a variable sensitivity of the scale at different disease stages, and provide important information for population selection and result interpretation in future clinical trials. [ABSTRACT FROM AUTHOR]

Published
2023
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14. What is the ideal endpoint in early-stage immunotherapy neoadjuvant trials in lung cancer?

Author

Cameron, Robert B., Hines, Jacobi B., Torri, Valter, Porcu, Luca, Donington, Jessica, Bestvina, Christine M., Vokes, Everett, Dolezal, James M., Esposito, Alessandra, and Garassino, Marina C.

Abstract

Numerous clinical trials investigating neoadjuvant immune checkpoint inhibitors (ICI) have been performed over the last 5 years. As the number of neoadjuvant trials increases, attention must be paid to identifying informative trial endpoints. Complete pathologic response has been shown to be an appropriate surrogate endpoint for clinical outcomes, such as event-free survival or overall survival, in breast cancer and bladder cancer, but it is less established for non-small-cell lung cancer (NSCLC). The simultaneous advances reported with adjuvant ICI make the optimal strategy for early-stage disease debatable. Considering the long time required to conduct trials, it is important to identify optimal endpoints and discover surrogate endpoints for survival that can help guide ongoing clinical research. Endpoints can be grouped into two categories: medical and surgical. Medical endpoints are measures of survival and drug activity; surgical endpoints describe the feasibility of neoadjuvant approaches at a surgical level as well as perioperative attrition and complications. There are also several exploratory endpoints, including circulating tumor DNA clearance and radiomics. In this review, we outline the advantages and disadvantages of commonly reported endpoints for clinical trials of neoadjuvant regimens in NSCLC. [ABSTRACT FROM AUTHOR]

Published
2023
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16. Molecular isoforms of high-mobility group box 1 are mechanistic biomarkers for epilepsy

Author

Walker, Lauren Elizabeth, Frigerio, Federica, Ravizza, Teresa, Ricci, Emanuele, Tse, Karen, Jenkins, Rosalind E., Sills, Graeme John, Jorgensen, Andrea, Porcu, Luca, Thippeswamy, Thimmasettappa, Alapirtti, Tiina, Peltola, Jukka, Brodie, Martin J., Park, Brian Kevin, Marson, Anthony Guy, Antoine, Daniel James, Vezzani, Annamaria, and Pirmohamed, Munir

Subjects
Epilepsy -- Physiological aspects, Bioassay -- Methods, Biological markers -- Health aspects, Health care industry
Abstract

Approximately 30% of epilepsy patients do not respond to antiepileptic drugs, representing an unmet medical need. There is evidence that neuroinflammation plays a pathogenic role in drug-resistant epilepsy. The high-mobility group box 1 (HMGB1)/TLR4 axis is a key initiator of neuroinflammation following epileptogenic injuries, and its activation contributes to seizure generation in animal models. However, further work is required to understand the role of HMGB1 and its isoforms in epileptogenesis and drug resistance. Using a combination of animal models and sera from clinically well-characterized patients, we have demonstrated that there are dynamic changes in HMGB1 isoforms in the brain and blood of animals undergoing epileptogenesis. The pathologic disulfide HMGB1 isoform progressively increased in blood before epilepsy onset and prospectively identified animals that developed the disease. Consistent with animal data, we observed early expression of disulfide HMGB1 in patients with newly diagnosed epilepsy, and its persistence was associated with subsequent seizures. In contrast with patients with well-controlled epilepsy, patients with chronic, drug-refractory epilepsy persistently expressed the acetylated, disulfide HMGB1 isoforms. Moreover, treatment of animals with antiinflammatory drugs during epileptogenesis prevented both disease progression and blood increase in HMGB1 isoforms. Our data suggest that HMGB1 isoforms are mechanistic biomarkers for epileptogenesis and drug-resistant epilepsy in humans, necessitating evaluation in larger-scale prospective studies., Introduction Epileptogenesis is a dynamic process of molecular, cellular, and functional reorganization following precipitating events that leads to brain pathology capable of generating spontaneous seizures (1). Currently used antiepileptic drugs [...]

Published
2017
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18. EOSC-Life Methodology framework to enhance reproducibility within EOSC-Life – revised version

Author

Bietrix, Florence, Carazo, José Maria, Capella-Gutierrez, Salvador, Coppens, Frederik, Chiusano, Maria Luisa, David, Romain, Fernandez, Jose Maria, Fratelli, Maddalena, Heriche, Jean-Karim, Goble, Carole, Gribbon, Philip, Holub, Petr, P. Joosten, Robbie, Leo, Simone, Owen, Stuart, Parkinson, Helen, Pieruschka, Roland, Pireddu, Luca, Porcu, Luca, Raess, Michael, Rodriguez-Navas, Laura, Scherer, Andreas, Soiland-Reyes, Stian, Tang, Jing, and Saunders, Gary

Subjects
Open Science, Life science research infrastructures, Data sharing, Data sharing tools, Reproducibility
Abstract

The original scope of task 8.3 is to develop a framework to assess the impact on reproducibility of the availability of life-science open data and workflows in the cloud. Such a framework should include the understanding of the tools and services produced and made available, the gaps they are filling up and their expected impact. A great part of the activities within EOSC-Life is actually related to reproducibility and provides in several ways tools that will have an impact. We describe here such activities and explain why and how they will have an impact on reproducibility in life sciences. In addition, for each action, we provide an indication of how we could measure its impact in practical ways, using adequate proxies. For these reasons, we changed the title of the deliverable, from “framework to assess ...” to “framework to enhance reproducibility”. First of all, we reasoned on what can be the contribution of open science to improve the reproducibility of research. Publicly sharing data, protocols, tools and computational workflows makes it possible to compare or combine the data and outcomes from different studies within a discipline as well as integrate data across scientific domains. It allows conclusions to be validated and possibly corrected as well as being reinforced by meta-analyses. Replication data and test/training data can also be used in many applications to contribute to reproducible research. Moreover, new hypotheses, different from the original aims of the study, can be explored. Datasets can be re-used to develop and test new methods, to conduct scientific and technical benchmarking activities and to support training activities. Therefore, in addition to generating more value from research investments, data sharing has the potential to increase confidence in research outcomes and increase knowledge dissemination. These benefits of open sharing have long been recognized in some fields such as bioinformatics, which has a long history of publicly sharing data with, for example, public repositories for nucleotide sequences going back 30 years and the Protein Data Bank (PDB), a repository of information about the 3D structures of proteins, nucleic acids, and complex assemblies, that celebrates its 50th birthday this year. In this notion, any improvement in sharing of data, tools and workflows among scientists and across disciplines, which is the aim of EOSC-Life and the wider EOSC, will contribute to reproducible science. In addition to this general scope, several specific actions to frame transparency in the reporting of experimental protocols, data and analytical workflows warrant the reproducibility of every single object (experimental results, data, or workflows) that is made available on the cloud. We describe here the initiatives in EOSC-Life to implement existing tools for reproducibility as well as to develop new tools for its enhancement. As the final goal of EOSC-Life is to make data resources available to the wider community of life scientists, although necessarily technical in several points, this document aims at a general readership, including experimental in addition to data scientists.

Published
2022

19. Cholesterol 24-hydroxylase is a novel pharmacological target for anti-ictogenic and disease modification effects in epilepsy

Author

Salamone, Alessia, primary, Terrone, Gaetano, additional, Di Sapia, Rossella, additional, Balosso, Silvia, additional, Ravizza, Teresa, additional, Beltrame, Luca, additional, Craparotta, Ilaria, additional, Mannarino, Laura, additional, Cominesi, Sara Raimondi, additional, Rizzi, Massimo, additional, Pauletti, Alberto, additional, Marchini, Sergio, additional, Porcu, Luca, additional, Zimmer, Till S., additional, Aronica, Eleonora, additional, During, Matthew, additional, Abrahams, Brett, additional, Kondo, Shinichi, additional, Nishi, Toshiya, additional, and Vezzani, Annamaria, additional

Published
2022
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22. Soluble stroma‐related biomarkers of pancreatic cancer

Author

Resovi, Andrea, Bani, Maria Rosa, Porcu, Luca, Anastasia, Alessia, Minoli, Lucia, Allavena, Paola, Cappello, Paola, Novelli, Francesco, Scarpa, Aldo, Morandi, Eugenio, Falanga, Anna, Torri, Valter, Taraboletti, Giulia, Belotti, Dorina, and Giavazzi, Raffaella

Published
2018
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24. A Definitive Prognostication System for Patients With Thoracic Malignancies Diagnosed With Coronavirus Disease 2019: An Update From the TERAVOLT Registry

Author

Whisenant, Jennifer G., primary, Baena, Javier, additional, Cortellini, Alessio, additional, Huang, Li-Ching, additional, Lo Russo, Giuseppe, additional, Porcu, Luca, additional, Wong, Selina K., additional, Bestvina, Christine M., additional, Hellmann, Matthew D., additional, Roca, Elisa, additional, Rizvi, Hira, additional, Monnet, Isabelle, additional, Boudjemaa, Amel, additional, Rogado, Jacobo, additional, Pasello, Giulia, additional, Leighl, Natasha B., additional, Arrieta, Oscar, additional, Aujayeb, Avinash, additional, Batra, Ullas, additional, Azzam, Ahmed Y., additional, Unk, Mojca, additional, Azab, Mohammed A., additional, Zhumagaliyeva, Ardak N., additional, Gomez-Martin, Carlos, additional, Blaquier, Juan B., additional, Geraedts, Erica, additional, Mountzios, Giannis, additional, Serrano-Montero, Gloria, additional, Reinmuth, Niels, additional, Coate, Linda, additional, Marmarelis, Melina, additional, Presley, Carolyn J., additional, Hirsch, Fred R., additional, Garrido, Pilar, additional, Khan, Hina, additional, Baggi, Alice, additional, Mascaux, Celine, additional, Halmos, Balazs, additional, Ceresoli, Giovanni L., additional, Fidler, Mary J., additional, Scotti, Vieri, additional, Métivier, Anne-Cécile, additional, Falchero, Lionel, additional, Felip, Enriqueta, additional, Genova, Carlo, additional, Mazieres, Julien, additional, Tapan, Umit, additional, Brahmer, Julie, additional, Bria, Emilio, additional, Puri, Sonam, additional, Popat, Sanjay, additional, Reckamp, Karen L., additional, Morgillo, Floriana, additional, Nadal, Ernest, additional, Mazzoni, Francesca, additional, Agustoni, Francesco, additional, Bar, Jair, additional, Grosso, Federica, additional, Avrillon, Virginie, additional, Patel, Jyoti D., additional, Gomes, Fabio, additional, Ibrahim, Ehab, additional, Trama, Annalisa, additional, Bettini, Anna C., additional, Barlesi, Fabrice, additional, Dingemans, Anne-Marie, additional, Wakelee, Heather, additional, Peters, Solange, additional, Horn, Leora, additional, Garassino, Marina Chiara, additional, and Torri, Valter, additional

Published
2022
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25. A definitive prognostication system for patients with thoracic malignancies diagnosed with COVID-19: an update from the TERAVOLT registry

Author

Whisenant, Jennifer G, Baena, Javier, Cortellini, Alessio, Huang, Li-Ching, Lo Russo, Giuseppe, Porcu, Luca, Wong, Selina K, Bestvina, Christine M, Hellmann, Matthew D, Roca, Elisa, Rizvi, Hira, Monnet, Isabelle, Boudjemaa, Amel, Rogado, Jacobo, Pasello, Giulia, Leighl, Natasha B, Arrieta, Oscar, Aujayeb, Avinash, Batra, Ullas, Azzam, Ahmed Y, Unk, Mojca, Azab, Mohammed A, Zhumagaliyeva, Ardak N, Gomez-Martin, Carlos, Blaquier, Juan B, Geraedts, Erica, Mountzios, Giannis, Serrano-Montero, Gloria, Reinmuth, Niels, Coate, Linda, Marmarelis, Melina, Presley, Carolyn J, Hirsch, Fred R, Garrido, Pilar, Khan, Hina, Baggi, Alice, Mascaux, Celine, Halmos, Balazs, Ceresoli, Giovanni L, Fidler, Mary J, Scotti, Vieri, Métivier, Anne-Cécile, Falchero, Lionel, Felip, Enriqueta, Genova, Carlo, Mazieres, Julien, Tapan, Umit, Brahmer, Julie, Bria, Emilio, Puri, Sonam, Popat, Sanjay, Reckamp, Karen L, Morgillo, Floriana, Nadal, Ernest, Mazzoni, Francesca, Agustoni, Francesco, Bar, Jair, Grosso, Federica, Avrillon, Virginie, Patel, Jyoti D, Gomes, Fabio, Ibrahim, Ehab, Trama, Annalisa, Bettini, Anna C, Barlesi, Fabrice, Dingemans, Anne-Marie, Wakelee, Heather, Peters, Solange, Horn, Leora, Garassino, Marina Chiara, and Torri, Valter

Subjects
TERAVOLT, Lung Neoplasms, thoracic, SARS-CoV-2, COVID-19, NSCLC, cancer, mortality, registry, Thoracic Neoplasms, Prognosis, C-Reactive Protein, COVID-19 Testing, Humans, Original Article, Registries, Retrospective Studies
Abstract

Patients with thoracic malignancies are at increased risk for mortality from coronavirus disease 2019 (COVID-19), and a large number of intertwined prognostic variables have been identified so far.Capitalizing data from the Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry, a global study created with the aim of describing the impact of COVID-19 in patients with thoracic malignancies, we used a clustering approach, a fast-backward step-down selection procedure, and a tree-based model to screen and optimize a broad panel of demographics and clinical COVID-19 and cancer characteristics.As of April 15, 2021, a total of 1491 consecutive eligible patients from 18 countries were included in the analysis. With a mean observation period of 42 days, 361 events were reported with an all-cause case fatality rate of 24.2%. The clustering procedure screened 73 covariates in 13 clusters. A further multivariable logistic regression for the association between clusters and death was performed, resulting in five clusters significantly associated with the outcome. The fast-backward step-down selection procedure then identified the following seven major determinants of death: Eastern Cooperative Oncology Group-performance status (ECOG-PS) (OR = 2.47, 1.87-3.26), neutrophil count (OR = 2.46, 1.76-3.44), serum procalcitonin (OR = 2.37, 1.64-3.43), development of pneumonia (OR = 1.95, 1.48-2.58), C-reactive protein (OR = 1.90, 1.43-2.51), tumor stage at COVID-19 diagnosis (OR = 1.97, 1.46-2.66), and age (OR = 1.71, 1.29-2.26). The receiver operating characteristic analysis for death of the selected model confirmed its diagnostic ability (area under the receiver operating curve = 0.78, 95% confidence interval: 0.75-0.81). The nomogram was able to classify the COVID-19 mortality in an interval ranging from 8% to 90%, and the tree-based model recognized ECOG-PS, neutrophil count, and c-reactive protein as the major determinants of prognosis.From 73 variables analyzed, seven major determinants of death have been identified. Poor ECOG-PS was found to have the strongest association with poor outcome from COVID-19. With our analysis, we provide clinicians with a definitive prognostication system to help determine the risk of mortality for patients with thoracic malignancies and COVID-19.

Published
2022

26. Association of Upfront Peptide Receptor Radionuclide Therapy With Progression-Free Survival Among Patients With Enteropancreatic Neuroendocrine Tumors

Author

Pusceddu, Sara, primary, Prinzi, Natalie, additional, Tafuto, Salvatore, additional, Ibrahim, Toni, additional, Filice, Angelina, additional, Brizzi, Maria Pia, additional, Panzuto, Francesco, additional, Baldari, Sergio, additional, Grana, Chiara M., additional, Campana, Davide, additional, Davì, Maria Vittoria, additional, Giuffrida, Dario, additional, Zatelli, Maria Chiara, additional, Partelli, Stefano, additional, Razzore, Paola, additional, Marconcini, Riccardo, additional, Massironi, Sara, additional, Gelsomino, Fabio, additional, Faggiano, Antongiulio, additional, Giannetta, Elisa, additional, Bajetta, Emilio, additional, Grimaldi, Franco, additional, Cives, Mauro, additional, Cirillo, Fernando, additional, Perfetti, Vittorio, additional, Corti, Francesca, additional, Ricci, Claudio, additional, Giacomelli, Luca, additional, Porcu, Luca, additional, Di Maio, Massimo, additional, Seregni, Ettore, additional, Maccauro, Marco, additional, Lastoria, Secondo, additional, Bongiovanni, Alberto, additional, Versari, Annibale, additional, Persano, Irene, additional, Rinzivillo, Maria, additional, Pignata, Salvatore Antonio, additional, Rocca, Paola Anna, additional, Lamberti, Giuseppe, additional, Cingarlini, Sara, additional, Puliafito, Ivana, additional, Ambrosio, Maria Rosaria, additional, Zanata, Isabella, additional, Bracigliano, Alessandra, additional, Severi, Stefano, additional, Spada, Francesca, additional, Andreasi, Valentina, additional, Modica, Roberta, additional, Scalorbi, Federica, additional, Milione, Massimo, additional, Sabella, Giovanna, additional, Coppa, Jorgelina, additional, Casadei, Riccardo, additional, Di Bartolomeo, Maria, additional, Falconi, Massimo, additional, and de Braud, Filippo, additional

Published
2022
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27. Neuroinflammation, body temperature and behavioural changes in CD1 male mice undergoing acute restraint stress: An exploratory study

Author

Redaelli, Veronica, primary, Bosi, Alice, additional, Luzi, Fabio, additional, Cappella, Paolo, additional, Zerbi, Pietro, additional, Ludwig, Nicola, additional, Di Lernia, Daniele, additional, Roughan, John Vincent, additional, Porcu, Luca, additional, Soranna, Davide, additional, Parati, Gianfranco, additional, and Calvillo, Laura, additional

Published
2021
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28. CXCL1-CXCR1/2 signaling is induced in human temporal lobe epilepsy and contributes to seizures in a murine model of acquired epilepsy

Author

Di Sapia, Rossella, primary, Zimmer, Till S., additional, Kebede, Valentina, additional, Balosso, Silvia, additional, Ravizza, Teresa, additional, Sorrentino, Diletta, additional, Castillo, Manuel Alejandro Montano, additional, Porcu, Luca, additional, Cattani, Franca, additional, Ruocco, Anna, additional, Aronica, Eleonora, additional, Allegretti, Marcello, additional, Brandolini, Laura, additional, and Vezzani, Annamaria, additional

Published
2021
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29. Doxycycline rescues recognition memory and circadian motor rhythmicity but does not prevent terminal disease in fatal familial insomnia mice

Author

Lavigna, Giada, primary, Masone, Antonio, additional, Bouybayoune, Ihssane, additional, Bertani, Ilaria, additional, Lucchetti, Jacopo, additional, Gobbi, Marco, additional, Porcu, Luca, additional, Zordan, Stefano, additional, Rigamonti, Mara, additional, Imeri, Luca, additional, Restelli, Elena, additional, and Chiesa, Roberto, additional

Published
2021
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32. EOSC-Life Methodology framework to enhance reproducibility within EOSC-Life

Author

Bietrix, Florence, Carazo, José Maria, Capella-Gutierrez, Salvador, Coppens, Frederik, Chiusano, Maria Luisa, David, Romain, Fernandez, Jose Maria, Fratelli, Maddalena, Heriche, Jean-Karim, Goble, Carole, Gribbon, Philip, Holub, Petr, P. Joosten, Robbie, Leo, Simone, Owen, Stuart, Parkinson, Helen, Pieruschka, Roland, Pireddu, Luca, Porcu, Luca, Raess, Michael, Rodriguez- Navas, Laura, Scherer, Andreas, Soiland-Reyes, Stian, and Tang, Jing

Subjects
Data sharing, Open science, Data sharing tools, Reproducibility
Abstract

The original scope of task 8.3 is to develop metrics to assess the impact on reproducibility of the availability of life-science open data and workflows in the cloud. A great part of the activities within EOSC-Life is actually related to reproducibility and provides in several ways tools that will have an impact. Therefore, we decided that it would be more informative to describe such activities and to explain why and how they will have an impact on reproducibility in life sciences, instead of providing abstract metrics for such an impact. For these reasons, we changed the title of the deliverable, from “framework to assess ...” to “framework to enhance reproducibility”. First of all, we reasoned on what can be the contribution of open science to improve the reproducibility of research. Publicly sharing data, protocols, tools and computational workflows makes it possible to compare or combine the data and outcomes from different studies within a discipline as well as integrate data across scientific domains. It allows conclusions to be validated and possibly corrected as well as being reinforced by meta-analyses. Replication data and test/training data can also be used in many applications to contribute to reproducible research. Moreover, new hypotheses, different from the original aims of the study, can be explored. Data sets can be re-used to develop and test new methods, to conduct scientific and technical benchmarking activities and to support training activities. Therefore, in addition to generating more value from research investments, data sharing has the potential to increase confidence in research outcomes and increase knowledge dissemination. These benefits of open sharing have long been recognized in some fields such as bioinformatics, which has a long history of publicly sharing data with, for example, public repositories for nucleotide sequences going back 30 years and the Protein Data Bank (PDB), a repository of information about the 3D structures of proteins, nucleic acids and complex assemblies, that celebrates its 50th birthday this year. In this notion, any improvement in sharing of data, tools and workflows among scientists and across disciplines, that is the aim of EOSC-Life and the wider EOSC, will contribute to reproducible science. In addition to this general scope, several specific actions to frame transparency in the reporting of experimental protocols, data and analytical workflows warrant the reproducibility of each single object (experimental results, data or workflows) that is made available on the cloud. We will describe here the initiatives in EOSC-Life to implement existing tools for reproducibility as well as to develop new tools for its enhancement. As the final goal of EOSC-Life is to make data resources available to the wider community of life scientists, although necessarily technical in several points, this document aims at a general readership, including experimental in addition to data scientists.

Published
2021

33. Drug Holidays and Overall Survival of Patients with Metastatic Colorectal Cancer

Author

Garattini, Silvio Ken, primary, Basile, Debora, additional, Bonotto, Marta, additional, Ongaro, Elena, additional, Porcu, Luca, additional, Corvaja, Carla, additional, Cattaneo, Monica, additional, Andreotti, Victoria Josephine, additional, Lisanti, Camilla, additional, Bertoli, Elisa, additional, Pelizzari, Giacomo, additional, Iacono, Donatella, additional, Miolo, Gianmaria, additional, Cardellino, Giovanni Gerardo, additional, Buonadonna, Angela, additional, Aprile, Giuseppe, additional, Fasola, Gianpiero, additional, Puglisi, Fabio, additional, and Pella, Nicoletta, additional

Published
2021
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34. Additional file 1 of PEGylated recombinant human hyaluronidase (PEGPH20) pre-treatment improves intra-tumour distribution and efficacy of paclitaxel in preclinical models

Author

Morosi, Lavinia, Meroni, Marina, Ubezio, Paolo, Fuso Nerini, Ilaria, Minoli, Lucia, Porcu, Luca, Panini, Nicolò, Colombo, Marika, Blouw, Barbara, Kang, David W., Davoli, Enrico, Zucchetti, Massimo, D’Incalci, Maurizio, and Frapolli, Roberta

Abstract

Additional file 1. Additional methods and results sections.

Published
2021
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35. Proposal for a clinical and an echocardiographic score for prediction of left atrial thrombosis in atrial fibrillation patients undergoing early electrical cardioversion

Author

Vincenti, A, Porcu, L, Sonaglioni, A, Genovesi, S, Vincenti, Antonio, Porcu, Luca, Sonaglioni, Andrea, Genovesi, Simonetta, Vincenti, A, Porcu, L, Sonaglioni, A, Genovesi, S, Vincenti, Antonio, Porcu, Luca, Sonaglioni, Andrea, and Genovesi, Simonetta

Abstract

Aims: Left atrial thrombosis (LAT) is usually detected by transesophageal echocardiography (TEE). Aim of the present study was to identify clinical and echocardiographic factors associated with left atrial thrombosis in atrial fibrillation (AF) patients undergoing early electrical cardioversion (ECV) in order to create scores that can predict LAT, in a non-invasive way. Methods: A consecutive cohort of patients with persistent AF scheduled for ECV was evaluated by transthoracic echocardiography and TEE. By a logistic regression model, variables significantly associated with LAT were assessed and introduced in predictive models to develop both a clinical and an echocardiographic prediction score for the presence of LAT. Results: 125 patients [median 71 (range 49-88) years, 60.0% males] were enrolled. Transesophageal echocardiography showed LAT in 35 patients (28%). The clinical variables significantly associated with LAT were previous stroke (OR=4.17), higher CHA2 DS2 -VASc score (OR=1.93), lower estimated glomerular filtration rate (OR=0.80), and higher brain natriuretic peptide levels (OR=1.44). Among echocardiographic parameters, E/e' ratio was directly associated with LAT (OR=2.25), while an inverse correlation was detected with left ventricular ejection fraction (OR=0.43) and total global left atrial strain (OR=0.59). Two prediction scores (clinical and echocardiographic) were developed. The positive predictive values of the clinical and the echocardiographic score were 80% and 100%, respectively, while the negative predictive values were 98% and 94%, respectively. Combined use of the scores reached a positive and negative predictive value of 100%. Conclusions: When providing concordant information the two scores are able to correctly identify patients with or without LAT. An external validation is necessary to demonstrate their usefulness in the clinical practice.

Published
2021

37. Additional file 2 of Effect of body mass index on response to neo-adjuvant therapy in HER2-positive breast cancer: an exploratory analysis of the NeoALTTO trial

Author

Cosimo, Serena Di, Porcu, Luca, Agbor-Tarh, Dominique, Cinieri, Saverio, Franzoi, Maria Alice, Santis, Maria Carmen De, Saura, Cristina, Huober, Jens, Fumagalli, Debora, Izquierdo, Miguel, Piccart, Martine, Daidone, Maria Grazia, and Azambuja, Evandro De

Abstract

Additional file 2: Supp. Figure 1 KM curve of Event free survival by BMI categories.

Published
2020
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38. Additional file 1 of Effect of body mass index on response to neo-adjuvant therapy in HER2-positive breast cancer: an exploratory analysis of the NeoALTTO trial

Author

Cosimo, Serena Di, Porcu, Luca, Agbor-Tarh, Dominique, Cinieri, Saverio, Franzoi, Maria Alice, Santis, Maria Carmen De, Saura, Cristina, Huober, Jens, Fumagalli, Debora, Izquierdo, Miguel, Piccart, Martine, Daidone, Maria Grazia, and Azambuja, Evandro De

Abstract

Additional file 1: Supp. Table 1 pCR rate according to BMI categories and treatment arms.

Published
2020
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39. Progression of Cerebellar Atrophy in Spinocerebellar Ataxia Type 2 Gene Carriers: A Longitudinal MRI Study in Preclinical and Early Disease Stages

Author

Nigri, Anna, primary, Sarro, Lidia, additional, Mongelli, Alessia, additional, Pinardi, Chiara, additional, Porcu, Luca, additional, Castaldo, Anna, additional, Ferraro, Stefania, additional, Grisoli, Marina, additional, Bruzzone, Maria Grazia, additional, Gellera, Cinzia, additional, Taroni, Franco, additional, Mariotti, Caterina, additional, and Nanetti, Lorenzo, additional

Published
2020
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40. Determinants of choice in offering drug holidays during first-line therapy for metastatic colorectal cancer

Author

Garattini, Silvio Ken, primary, Bonotto, Marta, additional, Porcu, Luca, additional, Ongaro, Elena, additional, Gerratana, Lorenzo, additional, Basile, Debora, additional, Parnofiello, Annamaria, additional, Pelizzari, Giacomo, additional, Cortiula, Francesco, additional, Corvaja, Carla, additional, Casagrande, Mariaelena, additional, Cardellino, Giovanni Gerardo, additional, Buonadonna, Angela, additional, Aprile, Giuseppe, additional, Puglisi, Fabio, additional, Fasola, Gianpiero, additional, and Pella, Nicoletta, additional

Published
2020
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43. Correction: Combination of PPARγ Agonist Pioglitazone and Trabectedin Induce Adipocyte Differentiation to Overcome Trabectedin Resistance in Myxoid Liposarcomas

Author

Frapolli, Roberta, primary, Bello, Ezia, additional, Ponzo, Marianna, additional, Craparotta, Ilaria, additional, Mannarino, Laura, additional, Ballabio, Sara, additional, Marchini, Sergio, additional, Carrassa, Laura, additional, Ubezio, Paolo, additional, Porcu, Luca, additional, Brich, Silvia, additional, Sanfilippo, Roberta, additional, Casali, Paolo Giovanni, additional, Gronchi, Alessandro, additional, Pilotti, Silvana, additional, and D'Incalci, Maurizio, additional

Published
2020
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45. Is There an Interplay between Immune Checkpoint Inhibitors, Thromboprophylactic Treatments and Thromboembolic Events? Mechanisms and Impact in Non-Small Cell Lung Cancer Patients

Author

Nichetti, Federico, primary, Ligorio, Francesca, additional, Zattarin, Emma, additional, Signorelli, Diego, additional, Prelaj, Arsela, additional, Proto, Claudia, additional, Galli, Giulia, additional, Marra, Antonio, additional, Apollonio, Giulia, additional, Porcu, Luca, additional, de Braud, Filippo, additional, Lo Russo, Giuseppe, additional, Ferrara, Roberto, additional, and Garassino, Marina Chiara, additional

Published
2019
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46. Combination of PPARγ Agonist Pioglitazone and Trabectedin Induce Adipocyte Differentiation to Overcome Trabectedin Resistance in Myxoid Liposarcomas

Author

Frapolli, Roberta, primary, Bello, Ezia, additional, Ponzo, Marianna, additional, Craparotta, Ilaria, additional, Mannarino, Laura, additional, Ballabio, Sara, additional, Marchini, Sergio, additional, Carrassa, Laura, additional, Ubezio, Paolo, additional, Porcu, Luca, additional, Brich, Silvia, additional, Sanfilippo, Roberta, additional, Casali, Paolo Giovanni, additional, Gronchi, Alessandro, additional, Pilotti, Silvana, additional, and D'Incalci, Maurizio, additional

Published
2019
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47. Interhemispherical Anatomical Disconnection in Disorders of Consciousness Patients

Author

Ferraro, Stefania, Nigri, Anna, Nava, Simone, Rosazza, Cristina Claudia, Sattin, Davide, Sebastiano, Davide Rossi, Porcu, Luca, Bruzzone, Maria Grazia, Marotta, Giorgio, Benti, Riccardo, Redolfi, Alberto, Matilde, Leonardi, D'Incerti, Ludovico, Andronache, Adrian, Fazio, Patrik, Caldiroli, Dario, Ciaraffa, Francesca, Covelli, Venusia, Giovannetti, Ambra, Minati, Ludovico, Molteni, Franco, Pagani, Marco, Panzica, Ferruccio, Parati, Eugenio A, Reggiori, Barbara, Rosazza, Cristina, Varotto, Giulia, Vela Gomez, Vela, and Visani, Elisa

Subjects
Adult, Male, 030506 rehabilitation, Pathology, medicine.medical_specialty, etiology, Corpus callosum, Corpus Callosum, White matter, corpus callosum, 03 medical and health sciences, 0302 clinical medicine, Level of consciousness, Humans, Medicine, In patient, disorders of consciousness, Aged, Persistent vegetative state, Aged, 80 and over, business.industry, Middle Aged, medicine.disease, diffusion tensor imaging, Magnetic Resonance Imaging, White Matter, brain metabolism, Diffusion Tensor Imaging, medicine.anatomical_structure, Etiology, Consciousness Disorders, Female, Neurology (clinical), Disconnection, 0305 other medical science, business, 030217 neurology & neurosurgery, Diffusion MRI
Abstract

In patients with disorder of consciousness (DOC), the corpus callosum (CC) and subcortical white matter (SWM) integrity were shown to discriminate between diagnostic categories. The aims of the study were: (1) to clarify the link between the integrity of CC and of SWM and the clinical status in DOC patients, disentangling the role played by the different brain injuries (traumatic or hemorrhagic brain injury); (2) to investigate the relationship between the CC integrity and the brain metabolism. We assessed the diagnostic accuracy of the CC and SWM integrity, using diffusion tensor imaging (DTI) and structural magnetic resonance imaging (sMRI), in a sample of DOC individuals, well balanced for diagnosis and etiology. The CC DTI-derived measures were correlated with the brain metabolism, computed with fluorodeoxyglucose positron emission tomography. Our results showed that the CC macrostructural DTI-derived measures discriminate between diagnosis and correlate with the clinical status of DOC patients irrespective of the etiology. Moreover, the CC DTI-derived measures strongly correlate with the metabolism of the right hemisphere. No significant diagnostic accuracy emerged for the CC sMRI evaluation and the SWM measures. Our results indicate that: (1) the degree of the interhemispherical anatomical disconnection is a marker of the level of consciousness independent from the type of brain injury; (2) CC alterations might be the consequence of the reduced brain metabolism. Remarkably, our results suggest that the functional interplay between the two hemispheres is linked tightly to the level of consciousness.

Published
2019

48. Combination of PPARg agonist pioglitazone and trabectedin induce adipocyte differentiation to overcome trabectedin resistance in myxoid liposarcomas

Author

Frapolli, R, Bello, E, Ponzo, M, Craparotta, I, Mannarino, L, Ballabio, S, Marchini, S, Carrassa, L, Ubezio, P, Porcu, L, Brich, S, Sanfilippo, R, Casali, P, Gronchi, A, Pilotti, S, D'Incalci, M, Frapolli, Roberta, Bello, Ezia, Ponzo, Marianna, Craparotta, Ilaria, Mannarino, Laura, Ballabio, Sara, Marchini, Sergio, Carrassa, Laura, Ubezio, Paolo, Porcu, Luca, Brich, Silvia, Sanfilippo, Roberta, Casali, Paolo Giovanni, Gronchi, Alessandro, Pilotti, Silvana, D'Incalci, Maurizio, Frapolli, R, Bello, E, Ponzo, M, Craparotta, I, Mannarino, L, Ballabio, S, Marchini, S, Carrassa, L, Ubezio, P, Porcu, L, Brich, S, Sanfilippo, R, Casali, P, Gronchi, A, Pilotti, S, D'Incalci, M, Frapolli, Roberta, Bello, Ezia, Ponzo, Marianna, Craparotta, Ilaria, Mannarino, Laura, Ballabio, Sara, Marchini, Sergio, Carrassa, Laura, Ubezio, Paolo, Porcu, Luca, Brich, Silvia, Sanfilippo, Roberta, Casali, Paolo Giovanni, Gronchi, Alessandro, Pilotti, Silvana, and D'Incalci, Maurizio

Abstract

Purpose: This study was aimed at investigating whether the PPARg agonist pioglitazone—given in combination with trabectedin—is able to reactivate adipocytic differentiation in myxoid liposarcoma (MLS) patient-derived xenografts, overcoming resistance to trabectedin. Experimental Design: The antitumor and biological effects of trabectedin, pioglitazone, and the combination of the two drugs were investigated in nude mice bearing well-characterized MLS xenografts representative of innate or acquired resistance against trabectedin. Pioglitazone and trabectedin were given by daily oral and weekly i.v. administrations, respectively. Molecular studies were performed by using microarrays approach, real-time PCR, and Western blotting. Results: We found that the resistance of MLS against trabectedin is associated with the lack of activation of adipogenesis. The PPARg agonist pioglitazone reactivated adipogenesis, assessed by histologic and gene pathway analyses. Pioglitazone was well tolerated and did not increase the toxicity of trabectedin. The ability of pioglitazone to reactivate adipocytic differentiation was observed by morphologic examination, and it is consistent with the increased expression of genes such as ADIPOQ implicated in the adipogenesis process. The determination of adiponectin by Western blotting constitutes a good and reliable biomarker related to MLS adipocytic differentiation. Conclusions: The finding that the combination of pioglitazone and trabectedin induces terminal adipocytic differentiation of some MLSs with the complete pathologic response and cure of tumor-bearing mice provides a strong rationale to test the combination of trabectedin and pioglitazone in patients with MLS.

Published
2019

49. Molecular isoforms of high-mobility group box 1 are mechanistic biomarkers for epilepsy

Author

Walker, Lauren Elizabeth, Frigerio, Federica, Ravizza, Teresa, Ricci, Emanuele, Tse, Karen, Jenkins, Rosalind E., Sills, Graeme John, Jorgensen, Andrea, Porcu, Luca, Thippeswamy, Thimmasettappa, Alapirtti, Tiina, Peltola, Jukka, Brodie, Martin J., Park, Brian Kevin, Marson, Anthony Guy, Antoine, Daniel James, Vezzani, Annamaria, and Pirmohamed, Munir

Subjects
Health care industry
Abstract

Following an inquiry at the University of Liverpool, the Editorial Board was recently informed that the mass spectrometry data provided by Daniel J. Antoine is unreliable and likely to be [...]

Published
2019
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50. A refinement approach in a mouse model of rehabilitation research. Analgesia strategy, reduction approach and infrared thermography in spinal cord injury

Author

Redaelli, Veronica, primary, Papa, Simonetta, additional, Marsella, Gerardo, additional, Grignaschi, Giuliano, additional, Bosi, Alice, additional, Ludwig, Nicola, additional, Luzi, Fabio, additional, Vismara, Irma, additional, Rimondo, Stefano, additional, Veglianese, Pietro, additional, Tepteva, Svetlana, additional, Mazzola, Silvia, additional, Zerbi, Pietro, additional, Porcu, Luca, additional, Roughan, John V., additional, Parati, Gianfranco, additional, and Calvillo, Laura, additional

Published
2019
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