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1. Autologous anti-GD2 CAR T cells efficiently target primary human glioblastoma

Author

Chiavelli, Chiara, Prapa, Malvina, Rovesti, Giulia, Silingardi, Marco, Neri, Giovanni, Pugliese, Giuseppe, Trudu, Lucia, Dall’Ora, Massimiliano, Golinelli, Giulia, Grisendi, Giulia, Vinet, Jonathan, Bestagno, Marco, Spano, Carlotta, Papapietro, Roberto Vito, Depenni, Roberta, Di Emidio, Katia, Pasetto, Anna, Nascimento Silva, Daniela, Feletti, Alberto, Berlucchi, Silvia, Iaccarino, Corrado, Pavesi, Giacomo, and Dominici, Massimo

Published
2024
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2. A Novel Prognostic Tool in Western and Eastern Biliary Tract Cancer Patients Treated in First-line Setting: the ECSIPOT Index

Author

Rovesti, Giulia, Leone, Francesco, Brandi, Giovanni, Cesario, Silvia, Scartozzi, Mario, Niger, Monica, Yoo, Changhoon, Filippi, Roberto, Casagrande, Mariaelena, Silvestris, Nicola, Santini, Daniele, Faloppi, Luca, Palloni, Andrea, Aglietta, Massimo, Bernardini, Laura, Cho, Hyungwoo, Lai, Eleonora, Fenocchio, Elisabetta, Pircher, Chiara, Iacono, Donatella, De Lorenzo, Stefania, Sperti, Elisa, Massa, Valentina, De Braud, Filippo, Jeong, Jae Ho, Aprile, Giuseppe, Burgio, Valentina, Cascinu, Stefano, and Casadei-Gardini, Andrea

Published
2022
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3. Prognostic Role of a New Index Tested in European and Korean Advanced Biliary Tract Cancer Patients: the PECS Index

Author

Rovesti, Giulia, Leone, Francesco, Brandi, Giovanni, Fornaro, Lorenzo, Scartozzi, Mario, Niger, Monica, Yoo, Changhoon, Caputo, Francesco, Filippi, Roberto, Casagrande, Mariaelena, Silvestris, Nicola, Santini, Daniele, Faloppi, Luca, Palloni, Andrea, Aglietta, Massimo, Vivaldi, Caterina, Cho, Hyungwoo, Lai, Eleonora, Fenocchio, Elisabetta, Nichetti, Federico, Pella, Nicoletta, De Lorenzo, Stefania, Di Maio, Massimo, Vasile, Enrico, de Braud, Filippo, Jeong, Jae Ho, Aprile, Giuseppe, Orsi, Giulia, Cascinu, Stefano, and Casadei-Gardini, Andrea

Published
2022
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7. Prognostic Role of Blood Eosinophil Count in Patients with Sorafenib-Treated Hepatocellular Carcinoma

Author

Orsi, Giulia, Tovoli, Francesco, Dadduzio, Vincenzo, Vivaldi, Caterina, Brunetti, Oronzo, Ielasi, Luca, Conti, Fabio, Rovesti, Giulia, Gramantieri, Laura, Rizzato, Mario Domenico, Pecora, Irene, Argentiero, Antonella, Teglia, Federica, Lonardi, Sara, Salani, Francesca, Granito, Alessandro, Zagonel, Vittorina, Marisi, Giorgia, Cabibbo, Giuseppe, Foschi, Francesco Giuseppe, Benevento, Francesca, Cucchetti, Alessandro, Piscaglia, Fabio, Cascinu, Stefano, Scartozzi, Mario, and Casadei-Gardini, Andrea

Published
2020
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11. Correction to: Prognostic Role of Blood Eosinophil Count in Patients with Sorafenib-Treated Hepatocellular Carcinoma

Author

Orsi, Giulia, Tovoli, Francesco, Dadduzio, Vincenzo, Vivaldi, Caterina, Brunetti, Oronzo, Ielasi, Luca, Conti, Fabio, Rovesti, Giulia, Gramantieri, Laura, Rizzato, Mario Domenico, Pecora, Irene, Argentiero, Antonella, Teglia, Federica, Lonardi, Sara, Salani, Francesca, Granito, Alessandro, Zagonel, Vittorina, Marisi, Giorgia, Cabibbo, Giuseppe, Foschi, Francesco Giuseppe, Benevento, Francesca, Cucchetti, Alessandro, Piscaglia, Fabio, Cascinu, Stefano, Scartozzi, Mario, and Casadei-Gardini, Andrea

Published
2020
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12. Supplementary Data from Association of NOS3 and ANGPT2 Gene Polymorphisms with Survival in Patients with Hepatocellular Carcinoma Receiving Sorafenib: Results of the Multicenter Prospective INNOVATE Study

Author

Casadei-Gardini, Andrea, primary, Marisi, Giorgia, primary, Dadduzio, Vincenzo, primary, Gramantieri, Laura, primary, Faloppi, Luca, primary, Ulivi, Paola, primary, Foschi, Francesco Giuseppe, primary, Tamburini, Emiliano, primary, Vivaldi, Caterina, primary, Rizzato, Mario Domenico, primary, Ielasi, Luca, primary, Canale, Matteo, primary, Conti, Fabio, primary, Rudnas, Britt, primary, Fornaro, Lorenzo, primary, Silvestris, Nicola, primary, Silletta, Marianna, primary, Cardellino, Giovanni Gerardo, primary, Lonardi, Sara, primary, Fornari, Francesca, primary, Orsi, Giulia, primary, Rovesti, Giulia, primary, Zagonel, Vittorina, primary, Cascinu, Stefano, primary, and Scartozzi, Mario, primary

Published
2023
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13. Soluble TRAIL Armed Human MSC As Gene Therapy For Pancreatic Cancer

Author

Spano, Carlotta, Grisendi, Giulia, Golinelli, Giulia, Rossignoli, Filippo, Prapa, Malvina, Bestagno, Marco, Candini, Olivia, Petrachi, Tiziana, Recchia, Alessandra, Miselli, Francesca, Rovesti, Giulia, Orsi, Giulia, Maiorana, Antonino, Manni, Paola, Veronesi, Elena, Piccinno, Maria Serena, Murgia, Alba, Pinelli, Massimo, Horwitz, Edwin M., Cascinu, Stefano, Conte, Pierfranco, and Dominici, Massimo

Published
2019
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14. Process Development for Adoptive Cell Therapy in Academia: A Pipeline for Clinical-Scale Manufacturing of Multiple TCR-T Cell Products

Author

Silva, Daniela Nascimento, primary, Chrobok, Michael, additional, Rovesti, Giulia, additional, Healy, Katie, additional, Wagner, Arnika Kathleen, additional, Maravelia, Panagiota, additional, Gatto, Francesca, additional, Mazza, Massimiliano, additional, Mazzotti, Lucia, additional, Lohmann, Volker, additional, Sällberg Chen, Margaret, additional, Sällberg, Matti, additional, Buggert, Marcus, additional, and Pasetto, Anna, additional

Published
2022
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17. A prognostic model in patients with advanced biliary tract cancer receiving first-line chemotherapy

Author

Filippi, Roberto, primary, Montagnani, Francesco, additional, Lombardi, Pasquale, additional, Fornaro, Lorenzo, additional, Aprile, Giuseppe, additional, Casadei-Gardini, Andrea, additional, Faloppi, Luca, additional, Palloni, Andrea, additional, Satolli, Maria Antonietta, additional, Scartozzi, Mario, additional, Citarella, Fabrizio, additional, Lutrino, Stefania Eufemia, additional, Vivaldi, Caterina, additional, Silvestris, Nicola, additional, Rovesti, Giulia, additional, Rimini, Margherita, additional, Aglietta, Massimo, additional, Brandi, Giovanni, additional, and Leone, Francesco, additional

Published
2021
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18. A Novel Prognostic Tool in Western and Eastern Biliary Tract Cancer Patients Treated in First-line Setting: the ECSIPOT Index

Author

Rovesti, Giulia, primary, Leone, Francesco, additional, Brandi, Giovanni, additional, Cesario, Silvia, additional, Scartozzi, Mario, additional, Niger, Monica, additional, Yoo, Changhoon, additional, Filippi, Roberto, additional, Casagrande, Mariaelena, additional, Silvestris, Nicola, additional, Santini, Daniele, additional, Faloppi, Luca, additional, Palloni, Andrea, additional, Aglietta, Massimo, additional, Bernardini, Laura, additional, Cho, Hyungwoo, additional, Lai, Eleonora, additional, Fenocchio, Elisabetta, additional, Pircher, Chiara, additional, Iacono, Donatella, additional, De Lorenzo, Stefania, additional, Sperti, Elisa, additional, Massa, Valentina, additional, De Braud, Filippo, additional, Jeong, Jae Ho, additional, Aprile, Giuseppe, additional, Burgio, Valentina, additional, Cascinu, Stefano, additional, and Casadei-Gardini, Andrea, additional

Published
2021
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19. Prognostic Role of a New Index Tested in European and Korean Advanced Biliary Tract Cancer Patients: the PECS Index

Author

Rovesti, Giulia, primary, Leone, Francesco, additional, Brandi, Giovanni, additional, Fornaro, Lorenzo, additional, Scartozzi, Mario, additional, Niger, Monica, additional, Yoo, Changhoon, additional, Caputo, Francesco, additional, Filippi, Roberto, additional, Casagrande, Mariaelena, additional, Silvestris, Nicola, additional, Santini, Daniele, additional, Faloppi, Luca, additional, Palloni, Andrea, additional, Aglietta, Massimo, additional, Vivaldi, Caterina, additional, Cho, Hyungwoo, additional, Lai, Eleonora, additional, Fenocchio, Elisabetta, additional, Nichetti, Federico, additional, Pella, Nicoletta, additional, De Lorenzo, Stefania, additional, Di Maio, Massimo, additional, Vasile, Enrico, additional, de Braud, Filippo, additional, Jeong, Jae Ho, additional, Aprile, Giuseppe, additional, Orsi, Giulia, additional, Cascinu, Stefano, additional, and Casadei-Gardini, Andrea, additional

Published
2021
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22. Effects of Metformin and Vitamin D on Clinical Outcome in Cholangiocarcinoma Patients

Author

Casadei-Gardini, Andrea, primary, Filippi, Roberto, additional, Rimini, Margherita, additional, Rapposelli, Ilario Giovanni, additional, Fornaro, Lorenzo, additional, Silvestris, Nicola, additional, Aldrighetti, Luca, additional, Aimar, Giacomo, additional, Rovesti, Giulia, additional, Bartolini, Giulia, additional, Vivaldi, Caterina, additional, Brunetti, Oronzo, additional, Sperti, Elisa, additional, La Face, Rosa, additional, Ratti, Francesca, additional, Andrikou, Kalliopi, additional, Valgiusti, Martina, additional, Bernardini, Laura, additional, Argentiero, Antonella, additional, Fenocchio, Elisabetta, additional, Frassineti, Giovanni Luca, additional, Cesario, Silvia, additional, Giovannelli, Francesco, additional, Quarà, Virginia, additional, Leone, Francesco, additional, and Cascinu, Stefano, additional

Published
2021
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23. Retrospective survival analysis in patients with metastatic pancreatic ductal adenocarcinoma with insulin-treated type 2 diabetes mellitus

Author

Pretta, Andrea, primary, Ziranu, Pina, additional, Puzzoni, Marco, additional, Lai, Eleonora, additional, Orsi, Giulia, additional, Liscia, Nicole, additional, Molinaro, Eleonora, additional, Mariani, Stefano, additional, Riggi, Laura, additional, Rovesti, Giulia, additional, Dubois, Marco, additional, Migliari, Marco, additional, Persano, Mara, additional, Saba, Giorgio, additional, Impera, Valentino, additional, Musio, Francesca, additional, Batzella, Erich, additional, Demurtas, Laura, additional, Pusceddu, Valeria, additional, Astara, Giorgio, additional, Faloppi, Luca, additional, Casadei Gardini, Andrea, additional, Andrikou, Kalliopi, additional, Cascinu, Stefano, additional, and Scartozzi, Mario, additional

Published
2020
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26. Association of NOS3 and ANGPT2 Gene Polymorphisms with Survival in Patients with Hepatocellular Carcinoma Receiving Sorafenib: Results of the Multicenter Prospective INNOVATE Study

Author

Casadei-Gardini, Andrea, primary, Marisi, Giorgia, additional, Dadduzio, Vincenzo, additional, Gramantieri, Laura, additional, Faloppi, Luca, additional, Ulivi, Paola, additional, Foschi, Francesco Giuseppe, additional, Tamburini, Emiliano, additional, Vivaldi, Caterina, additional, Rizzato, Mario Domenico, additional, Ielasi, Luca, additional, Canale, Matteo, additional, Conti, Fabio, additional, Rudnas, Britt, additional, Fornaro, Lorenzo, additional, Silvestris, Nicola, additional, Silletta, Marianna, additional, Cardellino, Giovanni Gerardo, additional, Lonardi, Sara, additional, Fornari, Francesca, additional, Orsi, Giulia, additional, Rovesti, Giulia, additional, Zagonel, Vittorina, additional, Cascinu, Stefano, additional, and Scartozzi, Mario, additional

Published
2020
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27. Validation and refinement of PROSASH model using the neutrophil‐to‐lymphocyte ratio in patients with HCC receiving sorafenib

Author

Casadei‐Gardini, Andrea, primary, Cabibbo, Giuseppe, additional, Dadduzio, Vincenzo, additional, Orsi, Giulia, additional, Vukotic, Ranka, additional, Rizzato, Mario Domenico, additional, Rossi, Margherita, additional, Guarneri, Valeria, additional, Lonardi, Sara, additional, D'Agostino, Dario, additional, Celsa, Ciro, additional, Rovesti, Giulia, additional, Rimini, Margherita, additional, Andreone, Pietro, additional, Zagonel, Vittorina, additional, Scartozzi, Mario, additional, Johnson, Philip, additional, Cascinu, Stefano, additional, and Cucchetti, Alessandro, additional

Published
2020
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28. 1H-NMR Based Serum Metabolomics Highlights Different Specific Biomarkers between Early and Advanced Hepatocellular Carcinoma Stages

Author

Casadei-Gardini, Andrea, primary, Del Coco, Laura, additional, Marisi, Giorgia, additional, Conti, Fabio, additional, Rovesti, Giulia, additional, Ulivi, Paola, additional, Canale, Matteo, additional, Frassineti, Giovanni Luca, additional, Foschi, Francesco Giuseppe, additional, Longo, Serena, additional, Fanizzi, Francesco Paolo, additional, and Giudetti, Anna Maria, additional

Published
2020
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29. Prognostic role of a new index (multi inflammatory index) in patients with metastatic colorectal cancer: results from the randomized ITACa trial

Author

Casadei Gardini, Andrea, primary, Scarpi, Emanuela, additional, Valgiusti, Martina, additional, Monti, Manlio, additional, Ruscelli, Silvia, additional, Matteucci, Laura, additional, Bartolini, Giulia, additional, Vertogen, Bernadette, additional, Pagan, Flavia, additional, Rovesti, Giulia, additional, Frassineti, Giovanni Luca, additional, and Passardi, Alessandro, additional

Published
2020
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30. ANGPT2 and NOS3 Polymorphisms and Clinical Outcome in Advanced Hepatocellular Carcinoma Patients Receiving Sorafenib

Author

Marisi, Giorgia, primary, Petracci, Elisabetta, additional, Raimondi, Francesco, additional, Faloppi, Luca, additional, Foschi, Francesco Giuseppe, additional, Lauletta, Gianfranco, additional, Iavarone, Massimo, additional, Canale, Matteo, additional, Valgiusti, Martina, additional, Neri, Luca Maria, additional, Ulivi, Paola, additional, Orsi, Giulia, additional, Rovesti, Giulia, additional, Vukotic, Ranka, additional, Conti, Fabio, additional, Cucchetti, Alessandro, additional, Ercolani, Giorgio, additional, Andrikou, Kalliopi, additional, Cascinu, Stefano, additional, Scartozzi, Mario, additional, and Casadei-Gardini, Andrea, additional

Published
2019
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31. Multicentric prospettive study of validation of angiogenesis-related gene polymorphisms in hepatocellular carcinoma patients treated with sorafenib: Interim analysis of INNOVATE study.

Author

Casadei Gardini, Andrea, primary, Marisi, Giorgia, additional, Dadduzio, Vincenzo, additional, Faloppi, Luca, additional, Ielasi, Luca, additional, Vivaldi, Caterina, additional, Rizzato, Mario Domenico, additional, Fornaro, Lorenzo, additional, Lonardi, Sara, additional, Gramantieri, Laura, additional, Pecora, Irene, additional, Foschi, Giuseppe Francesco, additional, Silvestris, Nicola, additional, Fornari, Francesca, additional, Orsi, Giulia, additional, Rovesti, Giulia, additional, Santini, Daniele, additional, Zagonel, Vittorina, additional, Cascinu, Stefano, additional, and Scartozzi, Mario, additional

Published
2019
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32. Retrospective survival analysis in patients with metastatic pancreatic ductal adenocarcinoma with insulin-treated type 2 diabetes mellitus

Author

Pretta, Andrea, Ziranu, Pina, Puzzoni, Marco, Lai, Eleonora, Orsi, Giulia, Liscia, Nicole, Molinaro, Eleonora, Mariani, Stefano, Riggi, Laura, Rovesti, Giulia, Dubois, Marco, Migliari, Marco, Persano, Mara, Saba, Giorgio, Impera, Valentino, Musio, Francesca, Batzella, Erich, Demurtas, Laura, Pusceddu, Valeria, Astara, Giorgio, Faloppi, Luca, Casadei Gardini, Andrea, Andrikou, Kalliopi, Cascinu, Stefano, and Scartozzi, Mario

Abstract

Introduction: The association between pancreatic ductal adenocarcinoma (PDAC) and type 2 diabetes mellitus (DM2) has long been evaluated and the role of antidiabetic medications such as metformin has also been investigated. The objective of this study was to examine the association between insulin use and overall survival (OS) in patients with advanced PDAC and DM2.Methods: We retrospectively collected data from 164 patients, including an exploratory cohort of 96 patients from Medical Oncology Unit, University Hospital and University of Cagliari, Italy, and a validation cohort of 68 patients from Medical Oncology of Modena University Hospital. Patients had metastatic disease and received a first-line gemcitabine-based chemotherapy and, subsequently, a second-line fluoropyrimidines-based chemotherapy. We performed univariate analysis to evaluate correlation between long-term diabetes and overall survival. Then we performed multivariate analysis, adjusting for sex, metastatic sites, Eastern Cooperative Oncology Group Performance Status, Ca19.9 levels, N/L ratio, and lactate dehydrogenase levels at diagnosis, to confirm the independence of the variable.Results: In the exploratory cohort, DM2 was significantly associated with higher median OS at univariate analysis (16 vs 10 months; p= 0.004). This result was confirmed by validation cohort (11 months vs 6 months; p= 0.01). In multivariate analysis, insulin-treated patients compared with non diabetic patients showed a significantly increased survival of 4.6 months (p= 0.03).Conclusions: Patients with insulin-treated metastatic PDAC showed better OS than non diabetic patients, as demonstrated by both cohorts. The correlation between OS and insulin-treated DM2 should be investigated further through a prospective clinical trial.

Published
2021
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33. Prognostic Role of a New Index (RAPID Index) in Advanced Hepatocellular Carcinoma Patients Receiving Sorafenib: Training and Validation Cohort

Author

Casadei-Gardini, Andrea, primary, Solaini, Leonardo, additional, Riggi, Laura, additional, Molinaro, Eleonora, additional, Dadduzio, Vincenzo, additional, Rizzato, Mario Domenico, additional, Pellino, Antonio, additional, Faloppi, Luca, additional, Marisi, Giorgia, additional, Ulivi, Paola, additional, Canale, Matteo, additional, Orsi, Giulia, additional, Rovesti, Giulia, additional, Andrikou, Kalliopi, additional, Spallanzani, Andrea, additional, Gelsomino, Fabio, additional, Foschi, Francesco Giuseppe, additional, Conti, Fabio, additional, Cucchetti, Alessandro, additional, Ercolani, Giorgio, additional, Biason, Paola, additional, Lonardi, Sara, additional, Cascinu, Stefano, additional, and Scartozzi, Mario, additional

Published
2019
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34. MSC-Delivered Soluble TRAIL and Paclitaxel as Novel Combinatory Treatment for Pancreatic Adenocarcinoma

Author

Rossignoli, Filippo, primary, Spano, Carlotta, additional, Grisendi, Giulia, additional, Foppiani, Elisabetta Manuela, additional, Golinelli, Giulia, additional, Mastrolia, Ilenia, additional, Bestagno, Marco, additional, Candini, Olivia, additional, Petrachi, Tiziana, additional, Recchia, Alessandra, additional, Miselli, Francesca, additional, Rovesti, Giulia, additional, Orsi, Giulia, additional, Veronesi, Elena, additional, Medici, Gregorio, additional, Petocchi, Benedetta, additional, Pinelli, Massimo, additional, Horwitz, Edwin M., additional, Conte, Pierfranco, additional, and Dominici, Massimo, additional

Published
2019
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35. Impact of Baseline Characteristics on the Overall Survival of HCC Patients Treated with Sorafenib: Ten Years of Experience

Author

Rovesti, Giulia, primary, Orsi, Giulia, additional, Kalliopi, Andrikou, additional, Vivaldi, Caterina, additional, Marisi, Giorgia, additional, Faloppi, Luca, additional, Foschi, Francesco Giuseppe, additional, Silvestris, Nicola, additional, Pecora, Irene, additional, Aprile, Giuseppe, additional, Molinaro, Eleonora, additional, Riggi, Laura, additional, Ulivi, Paola, additional, Canale, Matteo, additional, Cucchetti, Alessandro, additional, Tamburini, Emiliano, additional, Ercolani, Giorgio, additional, Fornaro, Lorenzo, additional, Andreone, Pietro, additional, Zavattari, Patrizia, additional, Scartozzi, Mario, additional, Cascinu, Stefano, additional, and Casadei-Gardini, Andrea, additional

Published
2019
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37. Could Inflammatory Indices and Metabolic Syndrome Predict the Risk of Cancer Development? Analysis from the Bagnacavallo Population Study.

Author

Rimini, Margherita, Casadei-Gardini, Andrea, Ravaioli, Alessandra, Rovesti, Giulia, Conti, Fabio, Borghi, Alberto, Dall'Aglio, Anna Chiara, Bedogni, Giorgio, Domenicali, Marco, Giacomoni, Pierluigi, Tiribelli, Claudio, Bucchi, Lauro, Falcini, Fabio, and Foschi, Francesco Giuseppe

Subjects
METABOLIC syndrome, CANCER, INVASIVE diagnosis, UNIVARIATE analysis, PHYSICAL activity
Abstract

Background: Despite the robust data available on inflammatory indices (neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)) and clinical outcome in oncological patients, their utility as a predictor of cancer incidence in the general population has not been reported in literature. Methods: The Bagnacavallo study was performed between October 2005 and March 2009. All citizens of Bagnacavallo (Ravenna, Emilia-Romagna, Italy) aged 30–60 years as of January 2005 were eligible and were invited by written letter to participate to the study. All participants underwent a detailed clinical history and physical examination following the model of the Dionysos Study. All blood values included in the analysis were obtained the day of physical examination. Cancer incidence data were obtained from the population-based Romagna Cancer Registry, which operates according to standard methods. The aim of this analysis was to examine the association between metabolic syndrome and baseline SII, NLR, and PLR levels, and the diagnosis of an invasive cancer in the Bagnacavallo study cohort. Results: At univariate analysis, metabolic syndrome was not associated with an increase of cancer incidence (HR 1.30; p = 0.155). High glucose (HR 1.49; p = 0.0.16), NLR HR 1.54, p = 0.002), PLR (HR 1.58, p = 0.001), and SII (HR 1.47, p = 0.006) were associated with an increase of cancer incidence. After adjusting for clinical covariates (smoking, physical activity, education, age, and gender) SII, PLR, and NLR remained independent prognostic factors for the prediction of cancer incidence. Conclusions: Inflammatory indices are promising, easy to perform, and inexpensive tools for identifying patients with higher risk of cancer in cancer-free population. [ABSTRACT FROM AUTHOR]

Published
2020
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38. Child Pugh and ALBI grade: past, present or future?

Author

Andrea Casadei-Gardini, Margherita Rimini, Giulia Rovesti, Rimini, Margherita, Rovesti, Giulia, and Casadei-Gardini, Andrea

Subjects
medicine.medical_specialty, Text mining, Editorial, business.industry, Family medicine, MEDLINE, Medicine, General Medicine, business
Published
2020

39. Prognostic Role of Blood Eosinophil Count in Patients with Sorafenib-Treated Hepatocellular Carcinoma

Author

Fabio Piscaglia, Irene Pecora, Luca Ielasi, Giulia Rovesti, Vittorina Zagonel, Vincenzo Dadduzio, Mario Domenico Rizzato, Alessandro Granito, Francesca Benevento, Giorgia Marisi, Oronzo Brunetti, Francesco Tovoli, Fabio Conti, Federica Teglia, Giuseppe Cabibbo, Giulia Orsi, Mario Scartozzi, Andrea Casadei-Gardini, Alessandro Cucchetti, Francesco Giuseppe Foschi, Laura Gramantieri, Francesca Salani, Stefano Cascinu, Sara Lonardi, Antonella Argentiero, Caterina Vivaldi, Orsi, G., Tovoli, F., Dadduzio, V., Vivaldi, C., Brunetti, O., Ielasi, L., Conti, F., Rovesti, G., Gramantieri, L., Rizzato, M. D., Pecora, I., Argentiero, A., Teglia, F., Lonardi, S., Salani, F., Granito, A., Zagonel, V., Marisi, G., Cabibbo, G., Foschi, F. G., Benevento, F., Cucchetti, A., Piscaglia, F., Cascinu, S., Scartozzi, M., Casadei-Gardini, A., Orsi G., Tovoli F., Dadduzio V., Vivaldi C., Brunetti O., Ielasi L., Conti F., Rovesti G., Gramantieri L., Rizzato M.D., Pecora I., Argentiero A., Teglia F., Lonardi S., Salani F., Granito A., Zagonel V., Marisi G., Cabibbo G., Foschi F.G., Benevento F., Cucchetti A., Piscaglia F., Cascinu S., Scartozzi M., Casadei-Gardini A., Orsi, Giulia, Tovoli, Francesco, Dadduzio, Vincenzo, Vivaldi, Caterina, Brunetti, Oronzo, Ielasi, Luca, Conti, Fabio, Rovesti, Giulia, Gramantieri, Laura, Rizzato, Mario Domenico, Pecora, Irene, Argentiero, Antonella, Teglia, Federica, Lonardi, Sara, Salani, Francesca, Granito, Alessandro, Zagonel, Vittorina, Marisi, Giorgia, Cabibbo, Giuseppe, Foschi, Francesco Giuseppe, Benevento, Francesca, Cucchetti, Alessandro, Piscaglia, Fabio, Cascinu, Stefano, Scartozzi, Mario, and Casadei-Gardini, Andrea

Subjects
0301 basic medicine, Oncology, Sorafenib, Adult, Male, Cancer Research, medicine.medical_specialty, Multivariate analysis, Carcinoma, Hepatocellular, Inflammation, Aged, Aged, 80 and over, Eosinophils, Female, Humans, Liver Neoplasms, Middle Aged, Prognosis, Survival Analysis, Young Adult, Capecitabine, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Regorafenib, 80 and over, medicine, Pharmacology (medical), Settore MED/12 - Gastroenterologia, business.industry, Carcinoma, Hepatocellular, hepatocellular carcinoma, Eosinophil, medicine.disease, Confidence interval, 030104 developmental biology, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, medicine.symptom, business, medicine.drug
Abstract

Background: Inflammation is a long-established hallmark of liver fibrosis and carcinogenesis. Eosinophils are emerging as crucial components of the inflammatory process influencing cancer development. The role of blood eosinophils in patients with hepatocellular carcinoma receiving systemic treatment is an unexplored field. Objective: The objective of this study was to analyse the prognostic role of the baseline eosinophil count in patients with sorafenib-treated hepatocellular carcinoma. Patients and Methods: A training cohort of 92 patients with advanced- or intermediate-stage sorafenib-treated hepatocellular carcinoma and two validation cohorts of 65 and 180 patients were analysed. Overall survival and progression-free survival in relation to baseline eosinophil counts were estimated by the Kaplan–Meier method. Univariate and multivariate analyses were performed. Results: A negative prognostic impact of low baseline eosinophil counts (< 50*109/L) was demonstrated in all cohorts (training cohort: hazard ratio = 50.1, 95% confidence interval 11.6–216.5, p < 0.0001 for low vs high eosinophil counts; first validation cohort: hazard ratio = 4.55, 95% confidence interval 1.24–16.65, p = 0.022; second validation cohort: hazard ratio = 3.21, 95% confidence interval 1.83–5.64, p < 0.0001). Moreover, low eosinophil counts had a negative prognostic role in patients progressing on or intolerant to sorafenib who received second-line regorafenib, but not capecitabine or best supportive care. Conclusions: Our analysis identified baseline blood eosinophil counts as a new prognostic factor in patients with sorafenib-treated hepatocellular carcinoma. Concerning second-line therapies, eosinophil counts were associated with survival outcomes only in regorafenib-treated patients, suggesting a possible predictive role in this setting.

Published
2020

40. Could Inflammatory Indices and Metabolic Syndrome Predict the Risk of Cancer Development? Analysis from the Bagnacavallo Population Study

Author

Margherita Rimini, Andrea Casadei-Gardini, Alessandra Ravaioli, Giulia Rovesti, Fabio Conti, Alberto Borghi, Anna Chiara Dall’Aglio, Giorgio Bedogni, Marco Domenicali, Pierluigi Giacomoni, Claudio Tiribelli, Lauro Bucchi, Fabio Falcini, Francesco Giuseppe Foschi, Bagnacavallo Study Group, Rimini, Margherita, Casadei-Gardini, Andrea, Ravaioli, Alessandra, Rovesti, Giulia, Conti, Fabio, Borghi, Alberto, Dall'Aglio, Anna Chiara, Bedogni, Giorgio, Domenicali, Marco, Giacomoni, Pierluigi, Tiribelli, Claudio, Bucchi, Lauro, Falcini, Fabio, Foschi, Francesco Giuseppe, Bagnacavallo Study Group, null, and Bagnacavallo Study Group, Null

Subjects
Metabolic Syndrome, lung cancer, breast cancer, cancer incidence, colon cancer, Inflammatory indices, lcsh:R, lcsh:Medicine, PLR, Inflammatory indice, Article, SII, NLR
Abstract

Background: Despite the robust data available on inflammatory indices (neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)) and clinical outcome in oncological patients, their utility as a predictor of cancer incidence in the general population has not been reported in literature. Methods: The Bagnacavallo study was performed between October 2005 and March 2009. All citizens of Bagnacavallo (Ravenna, Emilia-Romagna, Italy) aged 30–60 years as of January 2005 were eligible and were invited by written letter to participate to the study. All participants underwent a detailed clinical history and physical examination following the model of the Dionysos Study. All blood values included in the analysis were obtained the day of physical examination. Cancer incidence data were obtained from the population-based Romagna Cancer Registry, which operates according to standard methods. The aim of this analysis was to examine the association between metabolic syndrome and baseline SII, NLR, and PLR levels, and the diagnosis of an invasive cancer in the Bagnacavallo study cohort. Results: At univariate analysis, metabolic syndrome was not associated with an increase of cancer incidence (HR 1.30, p = 0.155). High glucose (HR 1.49, p = 0.0.16), NLR HR 1.54, p = 0.002), PLR (HR 1.58, p = 0.001), and SII (HR 1.47, p = 0.006) were associated with an increase of cancer incidence. After adjusting for clinical covariates (smoking, physical activity, education, age, and gender) SII, PLR, and NLR remained independent prognostic factors for the prediction of cancer incidence. Conclusions: Inflammatory indices are promising, easy to perform, and inexpensive tools for identifying patients with higher risk of cancer in cancer-free population.

Published
2020

41. Management of adverse events with tailored sorafenib dosing prolongs survival of hepatocellular carcinoma patients

Author

Alessandro Granito, Francesco Giuseppe Foschi, Giulia Rovesti, Giulia Negrini, Andrea Casadei-Gardini, Francesco Tovoli, Fabio Piscaglia, Giulia Orsi, Matteo Renzulli, Luca Ielasi, Tovoli, Francesco, Ielasi, Luca, CASADEI GARDINI, Andrea, Granito, Alessandro, Foschi, Francesco Giuseppe, Rovesti, Giulia, Negrini, Giulia, Orsi, Giulia, Renzulli, Matteo, Piscaglia, Fabio, Tovoli F., Ielasi L., Casadei-Gardini A., Granito A., Foschi F.G., Rovesti G., Negrini G., Orsi G., Renzulli M., and Piscaglia F.

Subjects
0301 basic medicine, Male, adverse events, hepatocellular carcinoma, learning curve, outcome, prognosis, sorafenib, Hepatocellular carcinoma, 0302 clinical medicine, Practice Patterns, Physicians', Outcome, Liver Neoplasms, Middle Aged, Sorafenib, Tolerability, Italy, 030211 gastroenterology & hepatology, Female, medicine.drug, Adverse event, medicine.medical_specialty, Carcinoma, Hepatocellular, Drug-Related Side Effects and Adverse Reactions, Medication Therapy Management, Prognosi, Antineoplastic Agents, 03 medical and health sciences, Internal medicine, medicine, Humans, Dosing, Adverse effect, Learning curve, No-Observed-Adverse-Effect Level, Duration of Therapy, Hepatology, Dose-Response Relationship, Drug, business.industry, Off-Label Use, medicine.disease, Survival Analysis, Discontinuation, Clinical trial, 030104 developmental biology, Sample size determination, business
Abstract

Sorafenib is associated with multiple adverse events (AEs), potentially causing its permanent interruption. The impact of the physicians experience on the management of these AEs and the relative implications on clinical outcomes are unknown. We verified if the AEs management changed over time and if these modifications impacted on treatment duration and overall survival (OS). Background & Aims: Sorafenib is associated with multiple adverse events (AEs), potentially causing its permanent interruption. It is unknown how physicians’ experience has impacted on the management of these AEs and consequently on clinical outcomes. We aimed to assess whether AE management changed over time and if these modifications impacted on treatment duration and overall survival (OS). Methods: We analysed the prospectively collected data of 338 consecutive patients who started sorafenib between January 2008 and December 2017 in 3 tertiary care centres in Italy. Patients were divided according to the starting date: Group A (2008–2012; n = 154), and Group B (2013–2017, n = 184). Baseline and follow-up data were compared. In the OS analysis, patients who received second-line treatments were censored when starting the new therapy. Results: Baseline characteristics, AEs, and radiological response were consistent across groups. Patients in Group B received a lower median daily dose (425 vs. 568 mg/day, p

Published
2019

42. Impact of Baseline Characteristics on the Overall Survival of HCC Patients Treated with Sorafenib: Ten Years of Experience

Author

Luca Faloppi, Francesco Giuseppe Foschi, Andrea Casadei-Gardini, Alessandro Cucchetti, Nicola Silvestris, Pietro Andreone, Matteo Canale, Laura Riggi, Giulia Rovesti, Irene Pecora, Emiliano Tamburini, Andrikou Kalliopi, Giulia Orsi, Stefano Cascinu, Caterina Vivaldi, Mario Scartozzi, Giuseppe Aprile, Giorgia Marisi, Patrizia Zavattari, Eleonora Molinaro, Lorenzo Fornaro, Giorgio Ercolani, Paola Ulivi, Rovesti, Giulia, Orsi, Giulia, Kalliopi, Andrikou, Vivaldi, Caterina, Marisi, Giorgia, Faloppi, Luca, Foschi, Francesco Giuseppe, Silvestris, Nicola, Pecora, Irene, Aprile, Giuseppe, Molinaro, Eleonora, Riggi, Laura, Ulivi, Paola, Canale, Matteo, Cucchetti, Alessandro, Tamburini, Emiliano, Ercolani, Giorgio, Fornaro, Lorenzo, Andreone, Pietro, Zavattari, Patrizia, Scartozzi, Mario, Cascinu, Stefano, Casadei-Gardini, Andrea, Rovesti, G, Orsi, G, Kalliopi, A, Vivaldi, C, Marisi, G, Faloppi, L, Foschi, Fg, Silvestris, N, Pecora, I, Aprile, G, Molinaro, E, Riggi, L, Ulivi, P, Canale, M, Cucchetti, A, Tamburini, E, Ercolani, G, Fornaro, L, Andreone, P, Zavattari, P, Scartozzi, M, Cascinu, S, and Casadei-Gardini, A

Subjects
Sorafenib, medicine.medical_specialty, Etiologies, Child-Pugh, Pharmaceutical Science, Aspartate transaminase, Etiologie, Gastroenterology, ECOG, ALBI grade, Baseline factors, Internal medicine, medicine, Lactate dehydrogenase, Neutrophil-to-lymphocyte ratio, Prognostic factor, Real-life conditions, Transaminases, Neutrophil to lymphocyte ratio, neoplasms, Real-life condition, Univariate analysis, biology, business.industry, medicine.disease, BCLC Stage, digestive system diseases, Portal vein thrombosis, Baseline factor, Hepatocellular carcinoma, biology.protein, Liver function, business, medicine.drug, Research Article
Abstract

Background: Sorafenib has been established as the standard of care for patients with advanced hepatocellular carcinoma (HCC) since 2007 on the basis of two landmark trials (SHARP and Asia-Pacific). Ten years have passed since then and, despite much research in the field, still no validated real-life prognostic markers are available for HCC patients treated with this drug. Therefore, going through 10 years of research into sorafenib of several Italian Cancer Centers, we conducted a field-practice study aimed at identifying baseline clinical factors that could be significantly associated with overall survival (OS). Method: Univariate/multivariate analyses were conducted to retrospectively identify the impact of baseline characteristics on the OS of 398 advanced HCC patients treated with sorafenib. Results: Based on univariate analysis, α-fetoprotein (AFP), albumin, AST, bilirubin, Child-Pugh, ECOG, systemic immune-inflammation index (SII), albumin-bilirubin (ALBI) grade, and portal vein thrombosis were significantly associated with shorter OS. Following adjustment for clinical covariates positive in univariate analysis, the multivariate analysis including AFP, age, etiology, albumin, aspartate transaminase (AST), bilirubin, Child-Pugh, LDH, platelet-to-lymphocyte ratio, ECOG, ALBI grade, portal vein thrombosis, SII, and BCLC stage identified increase in LDH, age >70 years, no viral etiologies, ECOG >0, albumin 40 as prognostic factors for poorer OS based on the 5% significance level. Conclusion: Our study highlights that baseline hepatic function, patient-centered variables, and etiology have prognostic value. These findings might have implications in terms of therapeutic decision-making and patient counseling.

Published
2019

43. Soluble TRAIL Armed Human MSC As Gene Therapy For Pancreatic Cancer

Author

Tiziana Petrachi, Malvina Prapa, Giulia Orsi, Olivia Candini, Marco Bestagno, Antonino Maiorana, Edwin M. Horwitz, Giulia Grisendi, Giulia Golinelli, Massimo Pinelli, Alba Murgia, Massimo Dominici, Pierfranco Conte, Giulia Rovesti, Elena Veronesi, Stefano Cascinu, Maria Serena Piccinno, Francesca Miselli, Paola Manni, Filippo Rossignoli, Alessandra Recchia, Carlotta Spano, Spano, Carlotta, Grisendi, Giulia, Golinelli, Giulia, Rossignoli, Filippo, Prapa, Malvina, Bestagno, Marco, Candini, Olivia, Petrachi, Tiziana, Recchia, Alessandra, Miselli, Francesca, Rovesti, Giulia, Orsi, Giulia, Maiorana, Antonino, Manni, Paola, Veronesi, Elena, Piccinno, Maria Serena, Murgia, Alba, Pinelli, Massimo, Horwitz, Edwin M., Cascinu, Stefano, Conte, Pierfranco, and Dominici, Massimo

Subjects
0301 basic medicine, Stromal cell, endocrine system diseases, Genetic enhancement, pancreatic cancer, lcsh:Medicine, Adipose tissue, Apoptosis, TRAIL, Adenocarcinoma, Article, TNF-Related Apoptosis-Inducing Ligand, MSC, Mice, 03 medical and health sciences, 0302 clinical medicine, Pancreatic cancer, Carcinoma, medicine, Animals, Humans, lcsh:Science, TRAIL, pancreatic cancer, gene therapy, MSC, Multidisciplinary, business.industry, lcsh:R, Mesenchymal stem cell, Mesenchymal Stem Cells, Genetic Therapy, medicine.disease, Xenograft Model Antitumor Assays, gene therapy, digestive system diseases, Pancreatic Neoplasms, Receptors, TNF-Related Apoptosis-Inducing Ligand, 030104 developmental biology, Cancer research, lcsh:Q, Stem cell, business, 030217 neurology & neurosurgery, Carcinoma, Pancreatic Ductal
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is still one of the most aggressive adult cancers with an unacceptable prognosis. For this reason novel therapies accounting for PDAC peculiarities, such as the relevant stromal reaction, are urgently needed. Here adipose mesenchymal stromal/stem cells (AD-MSC) have been armed to constantly release a soluble trimeric and multimeric variant of the known anti-cancer TNF-related apoptosis-inducing ligand (sTRAIL). This cancer gene therapy strategy was in vitro challenged demonstrating that sTRAIL was thermally stable and able to induce apoptosis in the PDAC lines BxPC-3, MIA PaCa-2 and against primary PDAC cells. sTRAIL released by AD-MSC relocated into the tumor stroma was able to significantly counteract tumor growth in vivo with a significant reduction in tumor size, in cytokeratin-7+ cells and by an anti-angiogenic effect. In parallel, histology on PDAC specimens form patients (n = 19) was performed to investigate the levels of TRAIL DR4, DR5 and OPG receptors generating promising insights on the possible clinical translation of our approach. These results indicate that adipose MSC can very efficiently vehicle a novel TRAIL variant opening unexplored opportunities for PDAC treatment.

Published
2019

44. Prognostic Role of a New Index (RAPID Index) in Advanced Hepatocellular Carcinoma Patients Receiving Sorafenib: Training and Validation Cohort

Author

Giulia Rovesti, Luca Faloppi, Fabio Gelsomino, Giorgio Ercolani, Eleonora Molinaro, Mario Domenico Rizzato, Andrea Casadei-Gardini, Alessandro Cucchetti, Kalliopi Andrikou, Laura Riggi, Stefano Cascinu, M. Scartozzi, Antonio Pellino, Matteo Canale, Fabio Conti, Giulia Orsi, Francesco Giuseppe Foschi, Sara Lonardi, Vincenzo Dadduzio, Giorgia Marisi, Andrea Spallanzani, Paola Ulivi, Paola Biason, Leonardo Solaini, Casadei-Gardini, A, Solaini, L, Riggi, L, Molinaro, E, Dadduzio, V, Rizzato, Md, Pellino, A, Faloppi, L, Marisi, G, Ulivi, P, Canale, M, Orsi, G, Rovesti, G, Andrikou, K, Spallanzani, A, Gelsomino, F, Foschi, Fg, Conti, F, Cucchetti, A, Ercolani, G, Biason, P, Lonardi, S, Cascinu, S, Scartozzi, M, Casadei-Gardini, Andrea, Solaini, Leonardo, Riggi, Laura, Molinaro, Eleonora, Dadduzio, Vincenzo, Rizzato, Mario Domenico, Pellino, Antonio, Faloppi, Luca, Marisi, Giorgia, Ulivi, Paola, Canale, Matteo, Orsi, Giulia, Rovesti, Giulia, Andrikou, Kalliopi, Spallanzani, Andrea, Gelsomino, Fabio, Foschi, Francesco Giuseppe, Conti, Fabio, Cucchetti, Alessandro, Ercolani, Giorgio, Biason, Paola, Lonardi, Sara, Cascinu, Stefano, and Scartozzi, Mario

Subjects
Sorafenib, medicine.medical_specialty, Index (economics), Lymphocyte, Pharmaceutical Science, Gastroenterology, chemistry.chemical_compound, Internal medicine, Lactate dehydrogenase, medicine, Neutrophil-to-lymphocyte ratio, Platelet-to-lymphocyte ratio, Systemic inflammatory index, α-Fetoprotein, In patient, Neutrophil to lymphocyte ratio, alpha-Fetoprotein, business.industry, medicine.disease, medicine.anatomical_structure, chemistry, Hepatocellular carcinoma, business, Validation cohort, Research Article, medicine.drug
Abstract

Background and Aims: The aim of the present study is to evaluate a new index influenced by the balance between the immune system, α-fetoprotein (AFP), and lactate dehydrogenase (LDH) (RAPID index) as a prognostic factor in patients treated with sorafenib. Methods: This study was conducted on a training cohort of 159 hepatocellular carcinoma (HCC) patients and a validation cohort of 68 HCC patients treated with sorafenib. The RAPID index was calculated as neutrophil/lymphocyte count × LDH × AFP. Results: In the training cohort, the median overall survival (OS) was 23.2 months (95% CI 11–25) and 12.1 months (95% CI 9–15) for patients with a low (≤3,226) and high (>3,226) RAPID index, respectively (ref. p = 0.017). Following adjustment for clinical covariates, multivariate analysis confirmed the RAPID index ≤3,226 versus >3,226 (HR = 0.37, 95% CI 0.18–0.74, p = 0.0054) as an independent prognostic factor for OS. In the validation cohort, the median OS was 26.9 months (95% CI 17.6–26.9) and 7.0 months (95% CI 6.2–9.2) for patients with a low (≤ 3,226) and high (>3,226) RAPID index, respectively (ref. p < 0.0001). Performing the same multivariate analysis of the training cohort (AFP, Eastern Cooperative Oncology Group, aspartate aminotransferase, neutrophil, platelet, systemic inflammatory index and RAPID index), the RAPID index 3,226 (HR = 3.86, 95% CI 1.45–10.29, p = 0.007) was found to be an independent prognostic factor for predicting OS. Conclusion: The low cost, easy assessment, and reproducibility of a full blood count make the RAPID index a promising tool for assessing HCC prognosis in future clinical practice.

Published
2019

45. Unlocking novel T cell-based immunotherapy for hepatocellular carcinoma through neoantigen-driven T cell receptor isolation.

Author

Maravelia P, Yao H, Cai C, Nascimento Silva D, Fransson J, Nilsson OB, Lu YW, Micke P, Botling J, Gatto F, Rovesti G, Carlsten M, Sallberg M, Stål P, Jorns C, Buggert M, and Pasetto A

Abstract

Background: Tumour-infiltrating T cells can mediate both antitumour immunity and promote tumour progression by creating an immunosuppressive environment. This dual role is especially relevant in hepatocellular carcinoma (HCC), characterised by a unique microenvironment and limited success with current immunotherapy., Objective: We evaluated T cell responses in patients with advanced HCC by analysing tumours, liver flushes and liver-draining lymph nodes, to understand whether reactive T cell populations could be identified despite the immunosuppressive environment., Design: T cells isolated from clinical samples were tested for reactivity against predicted neoantigens. Single-cell RNA sequencing was employed to evaluate the transcriptomic and proteomic profiles of antigen-experienced T cells. Neoantigen-reactive T cells expressing 4-1BB were isolated and characterised through T-cell receptor (TCR)-sequencing., Results: Bioinformatic analysis identified 542 candidate neoantigens from seven patients. Of these, 78 neoantigens, along with 11 hotspot targets from HCC driver oncogenes, were selected for ex vivo T cell stimulation. Reactivity was confirmed in co-culture assays for 14 targets, with most reactive T cells derived from liver flushes and lymph nodes. Liver flush-derived T cells exhibited central memory and effector memory CD4+ with cytotoxic effector profiles. In contrast, tissue-resident memory CD4+ and CD8+ T cells with an exhausted profile were primarily identified in the draining lymph nodes., Conclusion: These findings offer valuable insights into the functional profiles of neoantigen-reactive T cells within and surrounding the HCC microenvironment. T cells isolated from liver flushes and tumour-draining lymph nodes may serve as a promising source of reactive T cells and TCRs for further use in immunotherapy for HCC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Published
2025
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46. TRAIL receptors are expressed in both malignant and stromal cells in pancreatic ductal adenocarcinoma.

Author

Dall'Ora M, Rovesti G, Reggiani Bonetti L, Casari G, Banchelli F, Fabbiani L, Veronesi E, Petrachi T, Magistri P, Di Benedetto F, Spallanzani A, Chiavelli C, Spano MC, Maiorana A, Dominici M, and Grisendi G

Abstract

This study assesses the expression of all TNF-related apoptosis-inducing ligand (TRAIL) receptors in pancreatic ductal adenocarcinoma (PDAC) tumor tissue. We aimed to include TRAIL receptor expression as an inclusion parameter in a future clinical study using a TRAIL-based therapy approach for PDAC patients. Considering the emerging influence of PDAC desmoplastic stroma on the efficacy of anti-PDAC therapies, this analysis was extended to tumor stromal cells. Additionally, we performed PDAC stroma characterization. Our retrospective cohort study (N=50) included patients with histologically confirmed PDAC who underwent surgery. The expression of TRAIL receptors (DR4, DR5, DcR1, DcR2, and OPG) in tumor and stromal cells was evaluated by immunohistochemistry (IHC). The amount of tumor stroma was assessed by anti-vimentin IHC and Mallory's trichrome staining. The prognostic impact was determined by the univariate Cox proportional hazards regression model. An extensive expression of functional receptors DR4 and DR5 and a variable expression of decoy receptors were detected in PDAC tumor and stromal cells. Functional receptors were detected also in metastatic tumor and stromal cells. A poor prognosis was associated with low or absent expression of decoy receptors in tumor cells of primary PDAC. After assessing that almost 80% of tumor mass was composed of stroma, we correlated a cellular-dense stroma in primary PDAC with reduced relapse-free survival. We demonstrated that TRAIL functional receptors are widely expressed in PDAC, representing a promising target for TRAIL-based therapies. Further, we demonstrated that a low expression of DcR1 and the absence of OPG in tumor cells, as well as a cellular-dense tumor stroma, could negatively impact the prognosis of PDAC patients., Competing Interests: MD and GGr hold patents in the field of cell and gene therapy and declare a consultancy role, research funding, and stock ownership with Rigenerand Srl. MCS declares stock ownership with Rigenerand Srl. MDa and MCS are employees of Rigenerand Srl. The other authors do not declare any competing interests., (AJCR Copyright © 2021.)

Published
2021

47. 1 H-NMR Based Serum Metabolomics Highlights Different Specific Biomarkers between Early and Advanced Hepatocellular Carcinoma Stages.

Author

Casadei-Gardini A, Del Coco L, Marisi G, Conti F, Rovesti G, Ulivi P, Canale M, Frassineti GL, Foschi FG, Longo S, Fanizzi FP, and Giudetti AM

Abstract

The application of non-targeted serum metabolomics profiling represents a noninvasive tool to identify new clinical biomarkers and to provide early diagnostic differentiation, and insight into the pathological mechanisms underlying hepatocellular carcinoma (HCC) progression. In this study, we used proton Nuclear Magnetic Resonance ( 1 H-NMR) Spectroscopy and multivariate data analysis to profile the serum metabolome of 64 HCC patients, in early (n = 28) and advanced (n = 36) disease stages. We found that 1 H-NMR metabolomics profiling could discriminate early from advanced HCC patients with a cross-validated accuracy close to 100%. Orthogonal partial least squares discriminant analysis (OPLS-DA) showed significant changes in serum glucose, lactate, lipids and some amino acids, such as alanine, glutamine, 1-methylhistidine, lysine and valine levels between advanced and early HCC patients. Moreover, in early HCC patients, Kaplan-Meier analysis highlighted the serum tyrosine level as a predictor for overall survival (OS). Overall, our analysis identified a set of metabolites with possible clinical and biological implication in HCC pathophysiology.

Published
2020
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