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1. Mismatch Repair system protein deficiency as a resistance factor for locally advanced rectal adenocarcinoma patients receiving neoadjuvant chemo-radiotherapy

Author

Pretta, Andrea, Ziranu, Pina, Giampieri, Riccardo, Pinna, Giovanna, Randon, Giovanni, Donisi, Clelia, Ravarino, Alberto, Loi, Francesco, Deias, Giulia, Palmas, Enrico, Pretta, Gianluca, Morano, Federica, Semonella, Francesca, Mariani, Stefano, Deidda, Maria Assunta, Pusceddu, Valeria, Puzzoni, Marco, Lai, Eleonora, Solinas, Cinzia, Restivo, Angelo, Zorcolo, Luigi, Barbara, Raffaele, Berardi, Rossana, Faa, Gavino, Pietrantonio, Filippo, and Scartozzi, Mario

Published
2023
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2. CDX-2 expression correlates with clinical outcomes in MSI-H metastatic colorectal cancer patients receiving immune checkpoint inhibitors

Author

Ziranu, Pina, Pretta, Andrea, Pozzari, Marta, Maccioni, Antonio, Badiali, Manuela, Fanni, Daniela, Lai, Eleonora, Donisi, Clelia, Persano, Mara, Gerosa, Clara, Puzzoni, Marco, Bardanzellu, Fabio, Ambu, Rossano, Pusceddu, Valeria, Dubois, Marco, Cerrone, Giulia, Migliari, Marco, Murgia, Sara, Spanu, Dario, Pretta, Gianluca, Aimola, Valentina, Balconi, Francesca, Murru, Stefania, Faa, Gavino, and Scartozzi, Mario

Published
2023
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3. Clinical score for colorectal cancer patients with lung-limited metastases undergoing surgical resection: Meta-Lung Score

Author

Ziranu, Pina, Ferrari, Paolo Albino, Guerrera, Francesco, Bertoglio, Pietro, Tamburrini, Alessandro, Pretta, Andrea, Lyberis, Paraskevas, Grimaldi, Giulia, Lai, Eleonora, Santoru, Massimiliano, Bardanzellu, Fabio, Riva, Laura, Balconi, Francesca, Della Beffa, Eleonora, Dubois, Marco, Pinna-Susnik, Matteo, Donisi, Clelia, Capozzi, Enrico, Pusceddu, Valeria, Murenu, Alessandro, Puzzoni, Marco, Mathieu, Federico, Sarais, Sabrina, Alzetani, Aiman, Luzzi, Luca, Solli, Piergiorgio, Paladini, Piero, Ruffini, Enrico, Cherchi, Roberto, and Scartozzi, Mario

Published
2023
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4. A new prognostic tool for metastatic colorectal cancer patients receiving anti-angiogenic treatment, the PALM score: A single-center experience.

Author

Lai, Eleonora, primary, Palmas, Enrico, additional, Loi, Francesco, additional, Ziranu, Pina, additional, Mariani, Stefano, additional, Pretta, Andrea, additional, D'Agata, Alessandra Pia, additional, Dell'Utri, Veronica, additional, Papalexis, Giulia, additional, Deias, Giulia, additional, Rizzo, Daiana, additional, Spanu, Dario, additional, Sanna, Giorgia, additional, Moledda, Giusy, additional, Cadoni, Andrea, additional, Cucca, Mattia, additional, Donisi, Clelia, additional, Pusceddu, Valeria, additional, Puzzoni, Marco, additional, and Scartozzi, Mario, additional

Published
2024
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6. Prediction of Response to Anti-Angiogenic Treatment for Advanced Colorectal Cancer Patients: From Biological Factors to Functional Imaging

Author

Corrias, Giuseppe, primary, Lai, Eleonora, additional, Ziranu, Pina, additional, Mariani, Stefano, additional, Donisi, Clelia, additional, Liscia, Nicole, additional, Saba, Giorgio, additional, Pretta, Andrea, additional, Persano, Mara, additional, Fanni, Daniela, additional, Spanu, Dario, additional, Balconi, Francesca, additional, Loi, Francesco, additional, Deidda, Simona, additional, Restivo, Angelo, additional, Pusceddu, Valeria, additional, Puzzoni, Marco, additional, Solinas, Cinzia, additional, Massa, Elena, additional, Madeddu, Clelia, additional, Gerosa, Clara, additional, Zorcolo, Luigi, additional, Faa, Gavino, additional, Saba, Luca, additional, and Scartozzi, Mario, additional

Published
2024
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7. BRCA-mutant pancreatic ductal adenocarcinoma

Author

Lai, Eleonora, Ziranu, Pina, Spanu, Dario, Dubois, Marco, Pretta, Andrea, Tolu, Simona, Camera, Silvia, Liscia, Nicole, Mariani, Stefano, Persano, Mara, Migliari, Marco, Donisi, Clelia, Demurtas, Laura, Pusceddu, Valeria, Puzzoni, Marco, and Scartozzi, Mario

Published
2021
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8. The Role of p53 Expression in Patients with RAS/BRAF Wild-Type Metastatic Colorectal Cancer Receiving Irinotecan and Cetuximab as Later Line Treatment

Author

Ziranu, Pina, Lai, Eleonora, Schirripa, Marta, Puzzoni, Marco, Persano, Mara, Pretta, Andrea, Munari, Giada, Liscia, Nicole, Pusceddu, Valeria, Loupakis, Fotios, Demurtas, Laura, Libertini, Michela, Mariani, Stefano, Migliari, Marco, Dubois, Marco, Giampieri, Riccardo, Sotgiu, Giovanni, Dei Tos, Angelo Paolo, Lonardi, Sara, Zaniboni, Alberto, Fassan, Matteo, and Scartozzi, Mario

Published
2021
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9. Introducing immunotherapy for advanced hepatocellular carcinoma patients: Too early or too fast?

Author

Lai, Eleonora, Astara, Giorgio, Ziranu, Pina, Pretta, Andrea, Migliari, Marco, Dubois, Marco, Donisi, Clelia, Mariani, Stefano, Liscia, Nicole, Impera, Valentino, Persano, Mara, Tolu, Simona, Balconi, Francesca, Pinna, Giovanna, Spanu, Dario, Pireddu, Annagrazia, Saba, Giorgio, Camera, Silvia, Musio, Francesca, Puzzoni, Marco, Pusceddu, Valeria, Madeddu, Clelia, Casadei Gardini, Andrea, and Scartozzi, Mario

Published
2021
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11. Clinical characteristics and outcomes in patients with early-onset locally advanced rectal cancer.

Author

Pretta, Andrea, Ziranu, Pina, Giampieri, Riccardo, Donisi, Clelia, Randon, Giovanni, Moledda, Giusy, Morano, Federica, Spanu, Dario, Cadoni, Andrea, Cimbro, Erika, Dell'Utri, Veronica, Rizzo, Daiana, Codipietro, Claudia, Semonella, Francesca, Puzzoni, Marco, Pusceddu, Valeria, Zorcolo, Luigi, Berardi, Rossana, Pietrantonio, Filippo, and Scartozzi, Mario

Published
2024
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12. Clinical and prognostic characteristics of early onset metastatic pancreatic cancer.

Author

Pretta, Andrea, primary, Giampieri, Riccardo, additional, Nichetti, Federico, additional, Ziranu, Pina, additional, Lupi, Alessio, additional, Cimbro, Erika, additional, Andena, Paola, additional, Felicetti, Cristiano, additional, Pircher, Chiara Carlotta, additional, Gusmaroli, Eleonora, additional, Donisi, Clelia, additional, Balconi, Francesca, additional, Mariani, Stefano, additional, Lai, Eleonora, additional, Puzzoni, Marco, additional, Pusceddu, Valeria, additional, Berardi, Rossana, additional, Niger, Monica, additional, and Scartozzi, Mario, additional

Published
2024
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13. Comparison between different therapeutic sequences in patients affected by metastatic pancreatic ductal adenocarcinoma.

Author

Pretta, Andrea, primary, Giampieri, Riccardo, additional, Nichetti, Federico, additional, Ziranu, Pina, additional, Lupi, Alessio, additional, Moledda, Giusy, additional, Andena, Paola, additional, Felicetti, Cristiano, additional, D'Agata, Alessandra Pia, additional, Pircher, Chiara Carlotta, additional, Codipietro, Claudia, additional, Rota, Simone, additional, Rizzo, Daiana, additional, Sanna, Giorgia, additional, Lai, Eleonora, additional, Puzzoni, Marco, additional, Pusceddu, Valeria, additional, Berardi, Rossana, additional, Niger, Monica, additional, and Scartozzi, Mario, additional

Published
2024
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14. Prognostic factors for anti-angiogenic treatment in patients with metastatic colorectal cancer: New insights for an old issue from a single institution experience.

Author

Lai, Eleonora, primary, Ziranu, Pina, additional, Mariani, Stefano, additional, Loi, Francesco, additional, Palmas, Enrico, additional, D'Agata, Alessandra Pia, additional, Dell'Utri, Veronica, additional, Deias, Giulia, additional, Balconi, Francesca, additional, Rizzo, Daiana, additional, Papalexis, Giulia, additional, Codipietro, Claudia, additional, Sanna, Giorgia, additional, Moledda, Giusy, additional, Donisi, Clelia, additional, Spanu, Dario, additional, Pretta, Andrea, additional, Pusceddu, Valeria, additional, Puzzoni, Marco, additional, and Scartozzi, Mario, additional

Published
2024
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15. Early onset metastatic colorectal cancer: Clinical-prognostic characteristics and correlation to molecular profile.

Author

Pretta, Andrea, primary, Ziranu, Pina, additional, Perissinotto, Eleonora, additional, Ciracì, Paolo, additional, Giuliani, Lorenzo, additional, Pusceddu, Valeria, additional, De Grandis, Maria Caterina, additional, Taravella, Ada, additional, Puzzoni, Marco, additional, Piva, Vittoria Matilde, additional, Boccaccio, Chiara, additional, Lai, Eleonora, additional, Prete, Alessandra Anna Anna, additional, Cerma, Krisida, additional, Marmorino, Federica, additional, Giampieri, Riccardo, additional, Lonardi, Sara, additional, Cremolini, Chiara, additional, Bergamo, Francesca, additional, and Scartozzi, Mario, additional

Published
2024
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16. CD44: A New Prognostic Marker in Colorectal Cancer?

Author

Ziranu, Pina, Pretta, Andrea, Aimola, Valentina, Cau, Flaviana, Mariani, Stefano, D'Agata, Alessandra Pia, Codipietro, Claudia, Rizzo, Daiana, Dell'Utri, Veronica, Sanna, Giorgia, Moledda, Giusy, Cadoni, Andrea, Lai, Eleonora, Puzzoni, Marco, Pusceddu, Valeria, Castagnola, Massimo, Scartozzi, Mario, and Faa, Gavino

Subjects
PROTEINS, EPITHELIAL-mesenchymal transition, LIGANDS (Chemistry), CELL proliferation, HYALURONIC acid, COLORECTAL cancer, TUMOR markers, CELLULAR signal transduction, GENE expression, MEMBRANE glycoproteins, STEM cells, PATHOGENESIS, CELL receptors
Abstract

Simple Summary: CD44 is a crucial factor in colorectal cancer, with specific isoforms demonstrating their significance in the development, progression, metastasis, and resistance to therapy. Given the clinical and pathological impact of CD44, it represents a promising molecular target for cancer therapy. In this review, we aim to highlight the predictive and prognostic significance of CD44 in various cancer types, with a particular focus on colorectal cancer. Moreover, we evaluate current therapeutic interventions that target CD44 or reduce its expression, thereby highlighting its potential as an effective therapeutic strategy. Cluster of differentiation 44 (CD44) is a non-kinase cell surface glycoprotein. It is overexpressed in several cell types, including cancer stem cells (CSCs). Cells overexpressing CD44 exhibit several CSC traits, such as self-renewal, epithelial–mesenchymal transition (EMT) capability, and resistance to chemo- and radiotherapy. The role of CD44 in maintaining stemness and the CSC function in tumor progression is accomplished by binding to its main ligand, hyaluronan (HA). The HA-CD44 complex activates several signaling pathways that lead to cell proliferation, adhesion, migration, and invasion. The CD44 gene regularly undergoes alternative splicing, resulting in the standard (CD44s) and variant (CD44v) isoforms. The different functional roles of CD44s and specific CD44v isoforms still need to be fully understood. The clinicopathological impact of CD44 and its isoforms in promoting tumorigenesis suggests that CD44 could be a molecular target for cancer therapy. Furthermore, the recent association observed between CD44 and KRAS-dependent carcinomas and the potential correlations between CD44 and tumor mutational burden (TMB) and microsatellite instability (MSI) open new research scenarios for developing new strategies in cancer treatment. This review summarises current research regarding the different CD44 isoform structures, their roles, and functions in supporting tumorigenesis and discusses its therapeutic implications. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Immunotherapy and Cancer: The Multi-Omics Perspective.

Author

Donisi, Clelia, Pretta, Andrea, Pusceddu, Valeria, Ziranu, Pina, Lai, Eleonora, Puzzoni, Marco, Mariani, Stefano, Massa, Elena, Madeddu, Clelia, and Scartozzi, Mario

Subjects
MULTIOMICS, IMMUNOTHERAPY, CANCER treatment, TUMOR microenvironment, IMMUNE response
Abstract

Immunotherapies have revolutionized cancer treatment approaches. Because not all patients respond positively to immune therapeutic agents, it represents a challenge for scientists who strive to understand the mechanisms behind such resistance. In-depth exploration of tumor biology, using novel technologies such as omics science, can help decode the role of the tumor immune microenvironment (TIME) in producing a response to the immune blockade strategies. It can also help to identify biomarkers for patient stratification and personalized treatment. This review aims to explore these new models and highlight their possible pivotal role in changing clinical practice. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Immunonutrition supplementation for resectable gastric cancer during standard perioperative chemotherapy (CT) FLOT: A pivotal study, I–SUPPLY.

Author

Pusceddu, Valeria, primary, Donisi, Clelia, additional, Loi, Francesco, additional, Pretta, Andrea, additional, Mariani, Stefano, additional, Ziranu, Pina, additional, Puzzoni, Marco, additional, Lai, Eleonora, additional, Pozzari, Marta, additional, Cimbro, Erika, additional, Maccioni, Antonio, additional, Rizzo, Daiana, additional, Codipietro, Claudia, additional, Dell'Utri, Veronica, additional, D'Agata, Alessandra Pia, additional, Cadeddu, Michela, additional, and Scartozzi, Mario, additional

Published
2023
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19. Multimodal treatment of resectable pancreatic ductal adenocarcinoma

Author

Silvestris, Nicola, Brunetti, Oronzo, Vasile, Enrico, Cellini, Francesco, Cataldo, Ivana, Pusceddu, Valeria, Cattaneo, Monica, Partelli, Stefano, Scartozzi, Mario, Aprile, Giuseppe, Casadei Gardini, Andrea, Morganti, Alessio Giuseppe, Valentini, Vincenzo, Scarpa, Aldo, Falconi, Massimo, Calabrese, Angela, Lorusso, Vito, Reni, Michele, and Cascinu, Stefano

Published
2017
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20. Hepatocellular carcinoma and microbiota: Implications for clinical management and treatment

Author

Spanu, Dario, Pretta, Andrea, Lai, Eleonora, Persano, Mara, Donisi, Clelia, Mariani, Stefano, Dubois, Marco, Migliari, Marco, Saba, Giorgio, Ziranu, Pina, Pusceddu, Valeria, Puzzoni, Marco, Astara, Giorgio, and Scartozzi, Mario

Subjects
Science & Technology, Gastroenterology & Hepatology, Hepatology, Hepatocellular carcinoma, Gut-liver axis, Carcinogenesis, TRANSPLANTATION, TOLL-LIKE RECEPTOR-4, BREAST-CANCER CELLS, Gut microbiota, METABOLISM, CLOSTRIDIUM-DIFFICILE INFECTION, GUT MICROBIOME, Fecal microbiota transplantation, Immune checkpoint inhibitors, ALCOHOLIC LIVER-DISEASE, INTESTINAL MICROBIOTA, OBESITY, FECAL MICROBIOTA, Life Sciences & Biomedicine
Abstract

Gut microbiota plays an essential role in host homeostasis. It is involved in several physiological processes such as nutrients digestion and absorption, maintenance of intestinal epithelial barrier integrity and immune system self-tolerance. Especially the gut microbiota is assumed to play a crucial role in many gastrointestinal, pancreatic and liver disorders. Its role in hepatic carcinogenesis is also gaining increasing interest, especially regarding the development of therapeutic strategies. Different studies are highlighting a link between some bacterial strains and liver disease, including hepatocellular carcinoma (HCC). Indeed, HCC represents an interesting field of research in this perspective, due to the gut-liver axis, to the implication of microbiota in the immune system and to the increasing number of immunotherapy agents investigated in this tumour. Thus, the assessment of the role of microbiota in influencing clinical outcome for patients treated with these drugs is becoming of increasing importance. Our review aims to give an overview on the relationship between microbiota and HCC development/progression and treatment. We focus on potential implications on the available treatment strategies and those under study in the various stages of disease. We highlight the pathogenic mechanisms and investigate the underlying molecular pathways involved. Moreover, we investigate the potential prognostic and/or predictive role of microbiota for target therapies, immune checkpoint inhibitors and loco-regional treatment. Finally, given the limitation of current treatments, we analyze the gut microbiota-mediated therapies and its potential options for HCC treatment focusing on fecal microbiota transplantation. ispartof: WORLD JOURNAL OF HEPATOLOGY vol:14 issue:7 pages:1319-1332 ispartof: location:United States status: published

Published
2022

22. New Horizons in Metastatic Colorectal Cancer: Prognostic Role of CD44 Expression

Author

Ziranu, Pina, primary, Aimola, Valentina, additional, Pretta, Andrea, additional, Dubois, Marco, additional, Murru, Raffaele, additional, Liscia, Nicole, additional, Cau, Flaviana, additional, Persano, Mara, additional, Deias, Giulia, additional, Palmas, Enrico, additional, Loi, Francesco, additional, Migliari, Marco, additional, Pusceddu, Valeria, additional, Puzzoni, Marco, additional, Lai, Eleonora, additional, Cascinu, Stefano, additional, Faa, Gavino, additional, and Scartozzi, Mario, additional

Published
2023
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24. Influence of antidiabetic drugs on glucose metabolism and immune response in patients with metastatic pancreatic ductal adenocarcinoma receiving gemcitabine plus nab-paclitaxel as first-line treatment

Author

Pretta, Andrea, primary, Ziranu, Pina, additional, Giampieri, Riccardo, additional, Donisi, Clelia, additional, Cimbro, Erika, additional, Spanu, Dario, additional, Lai, Eleonora, additional, Pecci, Federica, additional, Balconi, Francesca, additional, Lupi, Alessio, additional, Pozzari, Marta, additional, Persano, Mara, additional, Murgia, Sara, additional, Pusceddu, Valeria, additional, Puzzoni, Marco, additional, Berardi, Rossana, additional, and Scartozzi, Mario, additional

Published
2022
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25. CDX-2 expression correlates with clinical outcomes in MSI-H metastatic colorectal cancer patients receiving immune checkpoint inhibitors

Author

Ziranu, Pina, primary, Pretta, Andrea, additional, Pozzari, Marta, additional, Maccioni, Antonio, additional, Badiali, Manuela, additional, Fanni, Daniela, additional, Lai, Eleonora, additional, Donisi, Clelia, additional, Persano, Mara, additional, Gerosa, Clara, additional, Puzzoni, Marco, additional, Bardanzellu, Fabio, additional, Ambu, Rossano, additional, Pusceddu, Valeria, additional, Dubois, Marco, additional, Cerrone, Giulia, additional, Migliari, Marco, additional, Murgia, Sara, additional, Spanu, Dario, additional, Pretta, Gianluca, additional, Aimola, Valentina, additional, Balconi, Francesca, additional, Murru, Stefania, additional, Faa, Gavino, additional, and Scartozzi, Mario, additional

Published
2022
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26. Influence of type 2 diabetes mellitus and concomitant anti-diabetic medications in patients with metastatic pancreatic ductal adenocarcinoma.

Author

Pretta, Andrea, primary, Cimbro, Erika, additional, Giampieri, Riccardo, additional, Spanu, Dario, additional, Lai, Eleonora, additional, Pecci, Federica, additional, Balconi, Francesca, additional, Lupi, Alessio, additional, Pozzari, Marta, additional, Murgia, Sara, additional, Bardanzellu, Fabio, additional, Maccioni, Antonio, additional, Contu, Fabiana, additional, Persano, Mara, additional, Donisi, Clelia, additional, Pusceddu, Valeria, additional, Puzzoni, Marco, additional, Ziranu, Pina, additional, Berardi, Rossana, additional, and Scartozzi, Mario, additional

Published
2022
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28. Influence of antidiabetic drugs on glucose metabolism and immune response in patients with metastatic pancreatic ductal adenocarcinoma receiving gemcitabine plus nab-paclitaxel as first-line treatment.

Author

Pretta, Andrea, Ziranu, Pina, Giampieri, Riccardo, Donisi, Clelia, Cimbro, Erika, Spanu, Dario, Lai, Eleonora, Pecci, Federica, Balconi, Francesca, Lupi, Alessio, Pozzari, Marta, Persano, Mara, Murgia, Sara, Pusceddu, Valeria, Puzzoni, Marco, Berardi, Rossana, and Scartozzi, Mario

Abstract

Association between pancreatic ductal adenocarcinoma (PDAC) and type 2 diabetes mellitus (DM2) has long been evaluated. Indeed, DM2 can be both an epiphenomenon of PDAC and a risk factor. The present study aimed to investigate the correlation between overall survival (OS) and antidiabetic drugs in patients with metastatic pancreatic ductal adenocarcinoma and DM2. Data from 232 patients were collected retrospectively from 2014 to 2021. 174 from AOU Cagliari Medical Oncology and 58 from AOU Ancona Medical Oncology. All patients received gemcitabine plus nab-paclitaxel first-line chemotherapy. We aimed to evaluate the correlation between DM2, anti-diabetic medications and overall survival. Survival distribution was assessed by Kaplan-Meier curves. Median age was 68±9, 127 (55%) were male. 138/232 (59%) patients were not affected by DM2, 94/232 (41%) were affected by DM2. 57 were insulin-treated and 37 were metformin-treated. DM2 treated patients showed an higher median overall survival (26 vs 12 months, p = 0,0002). Among DM2 patients insulin-treated and metformin-treated showed an mOS of 21 months and 33 months, respectively. Results showed a correlation between treated DM2 and higher mOS in patients with mPDAC. Limitations due to retrospective data collection must be considered. Further studies in this setting are needed. [ABSTRACT FROM AUTHOR]

Published
2023
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30. Liquid Biopsy-Driven Cetuximab Rechallenge Strategy in Molecularly Selected Metastatic Colorectal Cancer Patients

Author

Mariani, Stefano, primary, Puzzoni, Marco, additional, Giampieri, Riccardo, additional, Ziranu, Pina, additional, Pusceddu, Valeria, additional, Donisi, Clelia, additional, Persano, Mara, additional, Pinna, Giovanna, additional, Cimbro, Erika, additional, Parrino, Alissa, additional, Spanu, Dario, additional, Pretta, Andrea, additional, Lai, Eleonora, additional, Liscia, Nicole, additional, Lupi, Alessio, additional, Giglio, Enrica, additional, Palomba, Grazia, additional, Casula, Milena, additional, Pisano, Marina, additional, Palmieri, Giuseppe, additional, and Scartozzi, Mario, additional

Published
2022
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31. The interconnection between cellular metabolism and lymphocyte activation as a prognostic factor in patients affected by metastatic pancreatic ductal adenocarcinoma treated with gemcitabine and nab-paclitaxel as first line

Author

Andrea Pretta, Clelia Donisi, Riccardo Giampieri, Pina Ziranu, Erika Cimbro, Dario Spanu, Federica Pecci, Marco Migliari, Francesca Balconi, Alessio Lupi, Enrico Palmas, Giulia Deias, Benedetta Congiu, Marta Pozzari, Sara Murgia, Pusceddu Valeria, Marco Puzzoni, Eleonora Lai, Rossana Berardi, and Mario Scartozzi

Subjects
Cancer Research, Oncology
Abstract

752 Background: Glucose and other metabolites (lactates and glutamine) in the tumor microenvironment (TME) may alter the activity of the immune system cells. Cancer cells consume glucose and its decrease in the TME affects the function of tumour-infiltrating lymphocytes (TILs). Moreover, tumor-infiltrated immunosuppressive cells and vascular endothelial cells also deplete nutrients, in the TME, enhancing an immunosuppressive environment. On the basis of the results coming from our previous works regarding lymphocytes to monocytes ratio (LMr) and diabetes, suggesting a role for each of them as predictors of better outcomes, in this study we evaluate both of them in order to establish a possible role of them as outcomes predictive factors. Methods: Data from 228 patients (pts) were collected retrospectively from 2016 to 2021: 175 from the Medical Oncology Unit of University Hospital of Cagliari; 53 from the Medical Oncology Unit, AOU Ospedali Riuniti di Ancona. All pts had stage IV disease and received gemcitabine plus nab-paclitaxel 1st line chemotherapy. Statistical analysis was performed with the MedCalc package. We aimed to evaluate the correlation between treated DM2 and lymphocytes to monocytes ratio (LMr) ≥ 4 with outcomes. Survival distribution was assessed by Kaplan-Meier curves. Multivariate analysis was performed taking into consideration the following prognostic factors: sex, ECOG-PS, LMr, NLr, LDH, Ca19.9, and metastatic sites. Results: Median age was 68 (±9), 123/228 (54%) were male, 94/232 (40,6%) were affected by DM2 (insulin or metfomin-treated) and 138 (59,4%) pts were not affected by DM2. 52/228 (23%) pts had a LMr ≥ 4, 176/228 (77%) pts had a LMr < 4. In multivariate analysis, DM2 and LM ratio ≥ 4 were found to be independent factors associated with higher overall survival. Therefore, we divided the pts into 3 groups: co-presence DM2 and LM ≥ 4 (DM+LM+); absence of DM2 and LM ≥ 4 (DM-LM-); presence of DM2 or LM ≥ 4 (DM+LM- or DM-LM+). DM+LM+ demonstrated statistically significantly higher median OS than DM+LM-/DM-LM+ and DM-LM- (not reached versus 21 versus 9 months, respectively, p < 0.0001). Furthermore, DM+LM+ showed a statistically significant better median PFS than DM+LM-/DM-LM+ and DM-LM- (11 versus 9 versus 6 months, respectively, p = 0,0036). Conclusions: Results showed a correlation between pts with DM2/LMr ≥ 4 and better outcomes. This may suggest the presence of a link between glucose metabolism and lymphocytes activation. Antidiabetic medications could promote the inhibition of Warburg effect in tumor cells, and, consequently, provide a better glucose intake to extracellular microenvironment, and immune cells, including T lymphocytes. This process leads to a higher activity of T-cells and a better treatment response. Further studies are warranted.

Published
2023

32. Mismatch repair proteins (MMR) expression as predictive factor in locally advanced rectal cancer.

Author

Pretta, Andrea, primary, Donisi, Clelia, additional, Persano, Mara, additional, Pinna, Giovanna, additional, Cimbro, Erika, additional, Parrino, Alissa, additional, Aimola, Valentina, additional, Spanu, Dario, additional, Cerrone, Giulia, additional, Deidda, Simona, additional, Deidda, Maria Assunta, additional, Lai, Eleonora, additional, Pusceddu, Valeria, additional, Puzzoni, Marco, additional, Ziranu, Pina, additional, Barbara, Raffaele, additional, Restivo, Angelo, additional, Zorcolo, Luigi, additional, Faa, Gavino, additional, and Scartozzi, Mario, additional

Published
2022
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33. Uncovering key targets of success for immunotherapy in pancreatic cancer

Author

Pretta, Andrea, primary, Lai, Eleonora, additional, Persano, Mara, additional, Donisi, Clelia, additional, Pinna, Giovanna, additional, Cimbro, Erika, additional, Parrino, Alissa, additional, Spanu, Dario, additional, Mariani, Stefano, additional, Liscia, Nicole, additional, Dubois, Marco, additional, Migliari, Marco, additional, Impera, Valentino, additional, Saba, Giorgio, additional, Pusceddu, Valeria, additional, Puzzoni, Marco, additional, Ziranu, Pina, additional, and Scartozzi, Mario, additional

Published
2021
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34. Molecular-driven treatment for biliary tract cancer: the promising turning point

Author

Persano, Mara, primary, Puzzoni, Marco, additional, Ziranu, Pina, additional, Pusceddu, Valeria, additional, Lai, Eleonora, additional, Pretta, Andrea, additional, Donisi, Clelia, additional, Pinna, Giovanna, additional, Spanu, Dario, additional, Cimbro, Erika, additional, Parrino, Alissa, additional, Liscia, Nicole, additional, Mariani, Stefano, additional, Dubois, Marco, additional, Migliari, Marco, additional, and Scartozzi, Mario, additional

Published
2021
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35. Lymphocyte to monocyte ratio in metastatic pancreatic ductal adenocarcinoma as a prognostic factor and its potential role in identifying a subset of patients with a favorable response to therapy

Author

Andrea Pretta, Dario Spanu, Riccardo Giampieri, Eleonora Lai, Erika Cimbro, Federica Pecci, Francesca Balconi, Alessio Lupi, Marta Pozzari, Sara Murgia, Fabio Bardanzellu, Antonio Maccioni, Fabiana Contu, Mara Persano, Clelia Donisi, Pusceddu Valeria, Marco Puzzoni, Pina Ziranu, Rossana Berardi, and Mario Scartozzi

Subjects
Cancer Research, Oncology
Abstract

4153 Background: Despite the most recent therapeutic achievements, pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognosis and response to treatments. Among the most investigated prognostic biomarkers, the lymphocyte to monocyte ratio (LMr) is gaining increasing interest in literature, mostly in hematological malignancies, breast cancer, bladder cancer, non-small cell lung cancer, colorectal cancer, and resected pancreatic adenocarcinoma. In these settings, a higher LMr allows identifying a subset of patients with a better prognosis. Our study aimed to evaluate the role of the LMr as a prognostic factor in patients affected by metastatic PDAC and to find a cut-off value able to identify a subset of patients with better prognosis and possibly susceptible to other therapeutic options. Methods: Data from 228 patients were collected retrospectively from 2014 to 2021. 175 from the Department of Medical Oncology of the University Hospital of Cagliari and 53 from the Oncology Clinic - University Hospital of Ospedali Riuniti of Ancona. All patients had metastatic PDAC and blood samples were collected before starting first-line chemotherapy. The cut-off value for LMr was calculated according to the ROC curves at 6, 12, and 18 months. Kaplan-Meier curves were then obtained for the evaluation of survivals. Finally, multivariate analysis was performed, taking into consideration the following prognostic factors: sex, ECOG-PS, NL ratio, metastatic sites, Ca19.9 and LDH. Results: The median age was 68 y.o. (range 39-84 y.o.), 123 (54%) were males. Cut off value obtained for LMR, was 4. 156 (68,4%) patients had an LMr < 4 and 72 (31,6%) patients had an LMR ≥ 4. Patients with a ratio ≥ 4 showed a statistically significant difference in terms of median overall survival compared to patients with a ratio < 4 (23 months versus 11 months, p < 0.0001). First-line median progression-free survival was also different in patients with a value greater than or equal to 4 (11 months versus 6 months, p = 0.005), suggesting a better treatment response in the first group of patients. Finally, multivariate analysis showed that LMR ≥ 4 is an independent prognostic factor for OS ( p = 0.0005). Conclusions: The results of our study show that the lymphocyte to monocyte ratio could be an important prognostic factor in patients with metastatic pancreatic ductal adenocarcinoma, although the limitations of a retrospective study should be considered. Furthermore, these findings suggest the active role of the immune response in limiting disease progression, indicating a group of patients who could benefit most from a target or combined immunotherapy treatment.

Published
2022

36. Liquid biopsy-driven anti-EGFR rechallenge in patients with metastatic colorectal cancer.

Author

Mariani, Stefano, primary, Puzzoni, Marco, additional, Liscia, Nicole, additional, Impera, Valentino, additional, Pretta, Andrea, additional, Tolu, Simona, additional, Pireddu, Anna Grazia, additional, Persano, Mara, additional, Musio, Francesca, additional, Donisi, Clelia, additional, Pinna, Giovanna, additional, Lai, Eleonora, additional, Demurtas, Laura, additional, Ziranu, Pina, additional, Pusceddu, Valeria, additional, Pisano, Marina, additional, Palomba, Grazia, additional, Casula, Milena, additional, Palmieri, Giuseppe, additional, and Scartozzi, Mario, additional

Published
2021
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37. Oxaliplatin plus fluoropyrimidines as adjuvant therapy for colon cancer in older patients: A subgroup analysis from the TOSCA trial

Author

Rosati, Gerardo, primary, Lonardi, Sara, additional, Galli, Fabio, additional, Di Bartolomeo, Maria, additional, Ronzoni, Monica, additional, Zampino, Maria G., additional, Banzi, Maria, additional, Zaniboni, Alberto, additional, Pasini, Felice, additional, Bozzarelli, Silvia, additional, Garattini, Silvio K., additional, Ferrari, Daris, additional, Montesarchio, Vincenzo, additional, Mambrini, Andrea, additional, Ciuffreda, Libero, additional, Galli, Francesca, additional, Pusceddu, Valeria, additional, Carlomagno, Chiara, additional, Bidoli, Paolo, additional, Amoroso, Domenico, additional, Bochicchio, Anna M., additional, Frassineti, Luca, additional, Corsi, Domenico, additional, Bilancia, Domenico, additional, Pastorino, Alessandro, additional, De Stefano, Alfonso, additional, Labianca, Roberto, additional, Bilancia, D., additional, Rosati, G., additional, Montesarchio, V., additional, Iaffaioli, R.V., additional, Nasti, G., additional, Daniele, B., additional, Zagonel, V., additional, Lonardi, S., additional, Pella, N., additional, Aprile, G., additional, Pasini, F., additional, Marchetti, Roma P., additional, Romiti, A., additional, Ciuffreda, L., additional, Ferrari, D., additional, Foa, P., additional, Zaniboni, A., additional, Labianca, R., additional, Mosconi, S., additional, Sobrero, A., additional, Bidoli, P., additional, Cazzaniga, M., additional, Beretta, G.D., additional, Corsi, D.C., additional, Cortesi, E., additional, Barni, S., additional, Petrelli, F., additional, Allione, P., additional, D'Arco, A.M., additional, Valmadre, G., additional, Piazza, E., additional, Veltri, E., additional, Ramus, G. Vietti, additional, Giustini, L., additional, Tumulo, S., additional, Cascinu, S., additional, Granetto, C., additional, Testore, F., additional, Giordano, M., additional, Moroni, M., additional, Di Seri, M., additional, Nuzzo, A., additional, Angelelli, L., additional, Gori, S., additional, Farina, G., additional, Aglietta, M., additional, Franchi, R., additional, Comandé, M., additional, Giordani, P., additional, Tonini, G., additional, Bucci, E., additional, Ballestrero, A., additional, Benasso, M., additional, Graiff, C., additional, Bravi, S., additional, Caffo, O., additional, Silva, R.R., additional, Frontini, L., additional, Rota, S., additional, Cozzi, L., additional, Cantore, M., additional, Maiello, E., additional, Cinieri, S., additional, Silvestris, N., additional, Romito, S., additional, Gebbia, V., additional, Banzi, M., additional, Santoro, A., additional, Artioli, F., additional, Mattioli, R., additional, Contu, A., additional, Di Costanzo, F., additional, Leonardi, F., additional, Cavanna, L., additional, Passalacqua, R., additional, Amoroso, D., additional, Sozzi, P., additional, D'Amico, M., additional, Amadori, D., additional, Frassineti, L., additional, Turci, D., additional, Ravaioli, A., additional, Pasquini, E., additional, Gambi, A., additional, Faedi, M., additional, Cruciani, G., additional, Bajetta, E., additional, Di Bartolomeo, M., additional, Gianni, L., additional, Ronzoni, M., additional, Ionta, M.T., additional, Massidda, B., additional, Scartozzi, M., additional, Zampino, M.G., additional, Bochicchio, A.M., additional, Ciarlo, A., additional, Di Leo, A., additional, Frustaci, S., additional, Rangoni, G., additional, Arizzoia, A., additional, Pavesi, L., additional, Verusio, C., additional, Pinotti, G., additional, Iop, A., additional, De Placido, S., additional, Carlomagno, C., additional, Adamo, V., additional, Ficorella, C., additional, Natale, D., additional, Greco, E., additional, Rulli, E., additional, Galli, F., additional, Poli, D., additional, Porcu, L., additional, and Torri, V., additional

Published
2021
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38. 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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39. From CENTRAL to SENTRAL (SErum aNgiogenesis cenTRAL): Circulating Predictive Biomarkers to Anti-VEGFR Therapy

Author

Giampieri, Riccardo, primary, Ziranu, Pina, additional, Daniele, Bruno, additional, Zizzi, Antonio, additional, Ferrari, Daris, additional, Lonardi, Sara, additional, Zaniboni, Alberto, additional, Cavanna, Luigi, additional, Rosati, Gerardo, additional, Casagrande, Mariaelena, additional, Pella, Nicoletta, additional, Demurtas, Laura, additional, Zampino, Maria Giulia, additional, Sozzi, Pietro, additional, Pusceddu, Valeria, additional, Germano, Domenico, additional, Lai, Eleonora, additional, Zagonel, Vittorina, additional, Codecà, Carla, additional, Libertini, Michela, additional, Puzzoni, Marco, additional, Labianca, Roberto, additional, Cascinu, Stefano, additional, and Scartozzi, Mario, additional

Published
2020
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40. Molecular-Biology-Driven Treatment for Metastatic Colorectal Cancer

Author

Lai, Eleonora, primary, Liscia, Nicole, additional, Donisi, Clelia, additional, Mariani, Stefano, additional, Tolu, Simona, additional, Pretta, Andrea, additional, Persano, Mara, additional, Pinna, Giovanna, additional, Balconi, Francesca, additional, Pireddu, Annagrazia, additional, Impera, Valentino, additional, Dubois, Marco, additional, Migliari, Marco, additional, Spanu, Dario, additional, Saba, Giorgio, additional, Camera, Silvia, additional, Musio, Francesca, additional, Ziranu, Pina, additional, Puzzoni, Marco, additional, Demurtas, Laura, additional, Pusceddu, Valeria, additional, Dettori, Manuela, additional, Massa, Elena, additional, Atzori, Francesco, additional, Dessì, Mariele, additional, Astara, Giorgio, additional, Madeddu, Clelia, additional, and Scartozzi, Mario, additional

Published
2020
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41. Assessment of Duration and Effects of 3 vs 6 Months of Adjuvant Chemotherapy in High-Risk Stage II Colorectal Cancer

Author

Petrelli, Fausto, primary, Labianca, Roberto, additional, Zaniboni, Alberto, additional, Lonardi, Sara, additional, Galli, Fabio, additional, Rulli, Eliana, additional, Rosati, Gerardo, additional, Corallo, Salvatore, additional, Ronzoni, Monica, additional, Cardellino, Giovanni Gerardo, additional, Mattioli, Rodolfo, additional, Mambrini, Andrea, additional, Ciuffreda, Libero, additional, Banzi, Maria, additional, Pusceddu, Valeria, additional, Maiello, Evaristo, additional, Zampino, Maria, additional, Zagonel, Vittorina, additional, Marchetti, Paolo, additional, Corsi, Domenico, additional, Rimassa, Lorenza, additional, Cinieri, Saverio, additional, and Sobrero, Alberto, additional

Published
2020
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42. New therapeutic targets in pancreatic cancer

Author

Lai, Eleonora, primary, Puzzoni, Marco, additional, Ziranu, Pina, additional, Pretta, Andrea, additional, Impera, Valentino, additional, Mariani, Stefano, additional, Liscia, Nicole, additional, Soro, Paolo, additional, Musio, Francesca, additional, Persano, Mara, additional, Donisi, Clelia, additional, Tolu, Simona, additional, Balconi, Francesca, additional, Pireddu, Annagrazia, additional, Demurtas, Laura, additional, Pusceddu, Valeria, additional, Camera, Silvia, additional, Sclafani, Francesco, additional, and Scartozzi, Mario, additional

Published
2019
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44. 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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45. Molecular alterations in key-regulator genes among patients with T4 breast carcinoma

Author

Massidda Bruno, Sini MariaCristina, Budroni Mario, Atzori Francesco, Deidda MariaCristina, Pusceddu Valeria, Perra MariaTeresa, Sirigu Paola, Cossu Antonio, Palomba Grazia, Ionta MariaTeresa, and Palmieri Giuseppe

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Prognostic factors in patients who are diagnosed with T4 breast carcinomas are widely awaited. We here evaluated the clinical role of some molecular alterations involved in tumorigenesis in a well-characterized cohort of T4 breast cancer patients with a long follow-up period. Methods A consecutive series of 53 patients with T4 breast carcinoma was enrolled between 1992 and 2001 in Sardinia, and observed up for a median of 125 months. Archival paraffin-embedded tissue sections were used for immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analyses, in order to assess alterations in expression levels of survivin, p53, and pERK1-2 proteins as well as in amplification of CyclinD1 and h-prune genes. The Kaplan-Meier and Cox regression methods were used for survival assessment and statistical analysis. Results Overall, patients carrying increased expression of pERK1-2 (p = 0.027) and survivin (p = 0.008) proteins as well as amplification of h-prune gene (p = 0.045) presented a statistically-significant poorer overall survival in comparison with cases found negative for such alterations. After multivariate analysis, the pathological response to primary chemotherapy and the survivin overexpression in primary carcinoma represented the main parameters with a role as independent prognostic factors in our series. Conclusions Although retrospective, our study identified some molecular parameters with a significant impact on prediction of the response to therapy or prognosis among T4 breast cancer patients. Further large prospective studies are needed in order to validate the use of such markers for the management of these patients.

Published
2010
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46. Prognostic Value of Thyroid Hormone Ratios in Patients With Advanced Metastatic Colorectal Cancer Treated With Regorafenib: The TOREADOR Study

Author

Schirripa, Marta, primary, Pasqualetti, Giuseppe, additional, Giampieri, Riccardo, additional, Scartozzi, Mario, additional, Lonardi, Sara, additional, Rumanò, Laura, additional, Bergamo, Francesca, additional, Stragliotto, Silvia, additional, Murgioni, Sabina, additional, Alberti, Giulia, additional, Rizzato, Mario Domenico, additional, Prete, Alessandra Anna, additional, Puzzoni, Marco, additional, Pusceddu, Valeria, additional, Ziranu, Pina, additional, Pani, Fabiana, additional, Mariotti, Stefano, additional, Zagonel, Vittorina, additional, Monzani, Fabio, additional, and Loupakis, Fotios, additional

Published
2018
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47. BRAF-mutant colorectal cancer, a different breed evolving

Author

Lai, Eleonora, primary, Pretta, Andrea, additional, Impera, Valentino, additional, Mariani, Stefano, additional, Giampieri, Riccardo, additional, Casula, Laura, additional, Pusceddu, Valeria, additional, Coni, Pierpaolo, additional, Fanni, Daniela, additional, Puzzoni, Marco, additional, Demurtas, Laura, additional, Ziranu, Pina, additional, Faa, Gavino, additional, and Scartozzi, Mario, additional

Published
2018
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48. Sepolture tardo puniche dal Lotto 7 di Tuvixeddu: due storie di bambini mai nati e alcune osservazioni epigrafiche

Author

Salvi, Donatella, Sarigu, Marco, Pusceddu, Valeria, Zamora, José-Ángel, Zamora, José-Ángel [0000-0002-3245-4352], and Zamora, José-Ángel

Subjects
Black glossed ceramics, Punic inscriptions, Iscrizioni puniche, Tuvixeddu, Pregnant women, Necropolis, Necropoli, Ceramica a vernice nera, Donne gravide
Abstract

[EN] The excavation conducted in 2003 on the necropolis of Tuvixeddu identified two graves in which were buried two pregnant women who died before childbirth. Both tombs are part of a complex stratigraphy, with changes of funerary typology. The anthropological study concern the fetuses exceptionally preserved and allowed to establish their age. The next study examines two Punic inscriptions engraved on a bottom of a cup and on a small plate., [IT] In occasione dello scavo condotto nel 2003 alle pendici del colle di Tuvixeddu, sono state individuate due tombe a fossa nelle quali erano state deposte due donne, morte prima della nascita dei bambini che portavano in grembo. Entrambe le tombe fanno parte di una stratigrafia complessa, con modifica delle tipologie funerarie. Lo studio antropologico ha riguardato i feti e ha permesso di stabilirne l'età. Sono infine esaminati due interessanti graffiti punici tracciati su un fondo di coppa e su un piattello

Published
2016

50. The role of primary tumour sidedness, EGFR gene copy number and EGFR promoter methylation in RAS/BRAF wild-type colorectal cancer patients receiving irinotecan/cetuximab

Author

Demurtas, Laura, primary, Puzzoni, Marco, additional, Giampieri, Riccardo, additional, Ziranu, Pina, additional, Pusceddu, Valeria, additional, Mandolesi, Alessandra, additional, Cremolini, Chiara, additional, Masi, Gianluca, additional, Gelsomino, Fabio, additional, Antoniotti, Carlotta, additional, Loretelli, Cristian, additional, Meriggi, Fausto, additional, Zaniboni, Alberto, additional, Falcone, Alfredo, additional, Cascinu, Stefano, additional, and Scartozzi, Mario, additional

Published
2017
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