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3. Dissecting the genetic heterogeneity of gastric cancer

Author

Hess, Timo, Maj, Carlo, Gehlen, Jan, Borisov, Oleg, Haas, Stephan L., Gockel, Ines, Vieth, Michael, Piessen, Guillaume, Alakus, Hakan, Vashist, Yogesh, Pereira, Carina, Knapp, Michael, Schüller, Vitalia, Quaas, Alexander, Grabsch, Heike I., Trautmann, Jessica, Malecka-Wojciesko, Ewa, Mokrowiecka, Anna, Speller, Jan, Mayr, Andreas, Schröder, Julia, Hillmer, Axel M., Heider, Dominik, Lordick, Florian, Pérez-Aísa, Ángeles, Campo, Rafael, Espinel, Jesús, Geijo, Fernando, Thomson, Concha, Bujanda, Luis, Sopeña, Federico, Lanas, Ángel, Pellisé, María, Pauligk, Claudia, Goetze, Thorsten Oliver, Zelck, Carolin, Reingruber, Julian, Hassanin, Emadeldin, Elbe, Peter, Alsabeah, Sandra, Lindblad, Mats, Nilsson, Magnus, Kreuser, Nicole, Thieme, René, Tavano, Francesca, Pastorino, Roberta, Arzani, Dario, Persiani, Roberto, Jung, Jin-On, Nienhüser, Henrik, Ott, Katja, Schumann, Ralf R., Kumpf, Oliver, Burock, Susen, Arndt, Volker, Jakubowska, Anna, Ławniczak, Małgorzta, Moreno, Victor, Martín, Vicente, Kogevinas, Manolis, Pollán, Marina, Dąbrowska, Justyna, Salas, Antonio, Cussenot, Olivier, Boland-Auge, Anne, Daian, Delphine, Deleuze, Jean-Francois, Salvi, Erika, Teder-Laving, Maris, Tomasello, Gianluca, Ratti, Margherita, Senti, Chiara, De Re, Valli, Steffan, Agostino, Hölscher, Arnulf H., Messerle, Katharina, Bruns, Christiane Josephine, Sīviņš, Armands, Bogdanova, Inga, Skieceviciene, Jurgita, Arstikyte, Justina, Moehler, Markus, Lang, Hauke, Grimminger, Peter P., Kruschewski, Martin, Vassos, Nikolaos, Schildberg, Claus, Lingohr, Philipp, Ridwelski, Karsten, Lippert, Hans, Fricker, Nadine, Krawitz, Peter, Hoffmann, Per, Nöthen, Markus M., Veits, Lothar, Izbicki, Jakob R., Mostowska, Adrianna, Martinón-Torres, Federico, Cusi, Daniele, Adolfsson, Rolf, Cancel-Tassin, Geraldine, Höblinger, Aksana, Rodermann, Ernst, Ludwig, Monika, Keller, Gisela, Metspalu, Andres, Brenner, Hermann, Heller, Joerg, Neef, Markus, Schepke, Michael, Dumoulin, Franz Ludwig, Hamann, Lutz, Cannizzaro, Renato, Ghidini, Michele, Plaßmann, Dominik, Geppert, Michael, Malfertheiner, Peter, Gehlen, Olivier, Skoczylas, Tomasz, Majewski, Marek, Lubiński, Jan, Palmieri, Orazio, Boccia, Stefania, Latiano, Anna, Aragones, Nuria, Schmidt, Thomas, Dinis-Ribeiro, Mário, Medeiros, Rui, Al-Batran, Salah-Eddin, Leja, Mārcis, Kupcinskas, Juozas, García-González, María A., Venerito, Marino, and Schumacher, Johannes

Published
2023
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6. The potential of retinoic acid receptors as prognostic biomarkers and therapeutic targets in gastric cancer.

Author

Garattini, Silvio Ken, Basile, Debora, De Re, Valli', Brisotto, Giulia, Miolo, Gianmaria, Canzonieri, Vincenzo, Aprile, Giuseppe, Corvaja, Carla, Buriolla, Silvia, Garattini, Enrico, and Puglisi, Fabio

Subjects
GENE expression, RETINOIC acid receptors, STOMACH tumors, STOMACH cancer, ACUTE myeloid leukemia
Abstract

Background: Gastric cancer is a heterogeneous collection of tumors characterized by low survival rates. All-trans retinoic acid (retinoic-acid) is a clinically useful therapeutic agent belonging to the chemical family of retinoids, which consists of both natural and synthetic derivatives of vitamin-A. Retinoids are essential components of the normal diet and they regulate different physiological processes. From a therapeutic point of view, retinoic-acid is the first example of clinically useful differentiating agent. Indeed, the differentiating properties of this compound have promoted the use of retinoic-acid as a standard of care in Acute-Promyelocytic-Leukemia, a rare form of acute myeloid leukemia. In this study, we determine the RNA expression of the six isoforms of Retinoic-Acid-Receptors (RARα/RAR#946;/RAR#947;/RXR#945;/RXR#946;/RXR#947;) in view of their potential use as gastric cancer progression markers and/or therapeutic targets. In addition, we evaluate associations between the expression of these receptors and a simplified molecular classification of stomach tumors as well as the clinical characteristics of the cohort of patients analyzed. Finally, we define the prognostic value of the various Retinoic-Acid- Receptors in gastric cancer. Methods: In this single institution and retrospective RAR-GASTRIC study, we consider 55 consecutive gastric cancer patients. We extract total RNA from the pathological specimens and we perform a NanoString Assay using a customized panel of genes. This allows us to determine the expression levels of the RAR and RXR mRNAs as well as other transcripts of interest. Results: Our data demonstrate ubiquitous expression of the RAR and RXR mRNAs in gastric cancers. High levels of RAR#945;, RAR#946;, RXR#945; and RXR#946; show a significant association with stage IV tumors, "de novo" metastatic disease, microsatellite-stable-status, epithelial-to-mesenchymal-transition, as well as PIK3CA and TP53 expression. Finally, we observe a worse overall-survival in gastric cancer patients characterized by high RARα/RARβ/RARγ/RXRβ mRNA levels. Conclusions: In gastric cancer, high expression levels of RARa/RARb/RARg/RXRb transcripts are associated with poor clinical and molecular characteristics as well as with reduced overall-survival. Our data are consistent with the idea that RARα, RARβ, RARγ and RXRβ represent potential prognostic markers and therapeutic targets of gastric cancer. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Corrigendum to “Dissecting the genetic heterogeneity of gastric cancer”

Author

Hess, Timo, primary, Maj, Carlo, additional, Gehlen, Jan, additional, Borisov, Oleg, additional, Haas, Stephan L., additional, Gockel, Ines, additional, Vieth, Michael, additional, Piessen, Guillaume, additional, Alakus, Hakan, additional, Vashist, Yogesh, additional, Pereira, Carina, additional, Knapp, Michael, additional, Schüller, Vitalia, additional, Quaas, Alexander, additional, Grabsch, Heike I., additional, Trautmann, Jessica, additional, Malecka-Wojciesko, Ewa, additional, Mokrowiecka, Anna, additional, Speller, Jan, additional, Mayr, Andreas, additional, Schröder, Julia, additional, Hillmer, Axel M., additional, Heider, Dominik, additional, Lordick, Florian, additional, Pérez-Aísa, Ángeles, additional, Campo, Rafael, additional, Espinel, Jesús, additional, Geijo, Fernando, additional, Thomson, Concha, additional, Bujanda, Luis, additional, Sopeña, Federico, additional, Lanas, Ángel, additional, Pellisé, María, additional, Pauligk, Claudia, additional, Goetze, Thorsten Oliver, additional, Zelck, Carolin, additional, Reingruber, Julian, additional, Hassanin, Emadeldin, additional, Elbe, Peter, additional, Alsabeah, Sandra, additional, Lindblad, Mats, additional, Nilsson, Magnus, additional, Kreuser, Nicole, additional, Thieme, René, additional, Tavano, Francesca, additional, Pastorino, Roberta, additional, Arzani, Dario, additional, Persiani, Roberto, additional, Jung, Jin-On, additional, Nienhüser, Henrik, additional, Ott, Katja, additional, Schumann, Ralf R., additional, Kumpf, Oliver, additional, Burock, Susen, additional, Arndt, Volker, additional, Jakubowska, Anna, additional, Ławniczak, Małgorzta, additional, Moreno, Victor, additional, Martín, Vicente, additional, Kogevinas, Manolis, additional, Pollán, Marina, additional, Dąbrowska, Justyna, additional, Salas, Antonio, additional, Cussenot, Olivier, additional, Boland-Auge, Anne, additional, Daian, Delphine, additional, Deleuze, Jean-Francois, additional, Salvi, Erika, additional, Teder-Laving, Maris, additional, Tomasello, Gianluca, additional, Ratti, Margherita, additional, Senti, Chiara, additional, De Re, Valli, additional, Steffan, Agostino, additional, Hölscher, Arnulf H., additional, Messerle, Katharina, additional, Bruns, Christiane Josephine, additional, Sīviņš, Armands, additional, Bogdanova, Inga, additional, Skieceviciene, Jurgita, additional, Arstikyte, Justina, additional, Moehler, Markus, additional, Lang, Hauke, additional, Grimminger, Peter P., additional, Kruschewski, Martin, additional, Vassos, Nikolaos, additional, Schildberg, Claus, additional, Lingohr, Philipp, additional, Ridwelski, Karsten, additional, Lippert, Hans, additional, Fricker, Nadine, additional, Krawitz, Peter, additional, Hoffmann, Per, additional, Nöthen, Markus M., additional, Veits, Lothar, additional, Izbicki, Jakob R., additional, Mostowska, Adrianna, additional, Martinón-Torres, Federico, additional, Cusi, Daniele, additional, Adolfsson, Rolf, additional, Cancel-Tassin, Geraldine, additional, Höblinger, Aksana, additional, Rodermann, Ernst, additional, Ludwig, Monika, additional, Keller, Gisela, additional, Metspalu, Andres, additional, Brenner, Hermann, additional, Heller, Joerg, additional, Neef, Markus, additional, Schepke, Michael, additional, Dumoulin, Franz Ludwig, additional, Hamann, Lutz, additional, Cannizzaro, Renato, additional, Ghidini, Michele, additional, Plaßmann, Dominik, additional, Geppert, Michael, additional, Malfertheiner, Peter, additional, Glehen, Olivier, additional, Skoczylas, Tomasz, additional, Majewski, Marek, additional, Lubiński, Jan, additional, Palmieri, Orazio, additional, Boccia, Stefania, additional, Latiano, Anna, additional, Aragones, Nuria, additional, Schmidt, Thomas, additional, Dinis-Ribeiro, Mário, additional, Medeiros, Rui, additional, Al-Batran, Salah-Eddin, additional, Leja, Mārcis, additional, Kupcinskas, Juozas, additional, García-González, María A., additional, Venerito, Marino, additional, and Schumacher, Johannes, additional

Published
2023
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14. Preliminary Study of the Relationship between Osteopontin and Relapsed Hodgkin's Lymphoma.

Author

De Re, Valli, Lopci, Egesta, Brisotto, Giulia, Elia, Caterina, Mussolin, Lara, Mascarin, Maurizio, and d'Amore, Emanuele Stefano Giovanni

Subjects
HODGKIN'S disease, OSTEOPONTIN, POSITRON emission tomography, DENDRITIC cells
Abstract

The primary objective of this study was to investigate the potential role of tissue osteopontin, also known as secreted phosphoprotein 1 (SPP1), as a contributing factor to an unfavorable prognosis in classical Hodgkin's lymphoma (HL) patients who received the same treatment protocol. The study involved 44 patients aged 4–22 years, with a median follow-up period of 3 years. Patients with higher levels of SPP1 were associated with tissue necrosis and inflammation, and there was a trend toward a poorer prognosis in this group. Before therapy, we found a correlation between positron emission tomography (PET) scans and logarithmic SPP1 levels (p = 0.035). However, the addition of SPP1 levels did not significantly enhance the predictive capacity of PET scans for recurrence or progression. Elevated SPP levels were associated with tissue mRNA counts of chemotactic and inflammatory chemokines, as well as specific monocyte/dendritic cell subtypes, defined by IL-17RB, PLAUR, CXCL8, CD1A, CCL13, TREM1, and CCL24 markers. These findings contribute to a better understanding of the potential factors influencing the prognosis of HL patients and the potential role of SPP1 in the disease. While the predictive accuracy of PET scans did not substantially improve during the study, the results underscore the complexity of HL and highlight the relationships between SPP1 and other factors in the context of HL relapse. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Molecular Features Distinguishing Gastric Cancer Subtypes

Author

De Re, Valli

Abstract

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Stomach cancers are 90% adenocarcinoma; lymphoma, carcinoid, and stromal tumours may occur. Adenocarcinoma can be subdivided into histological Lauren and the World Health Organization (WHO) classifications, but this information has not led to the development of histologic subtype-specific treatment options. One way to potentially improve treatment for gastric cancers is to better understand the pathogenesis of this disease, the contribution of Helicobacter pylori infection, and host immune response to lead to the development of integrated histological and molecular classification schemes for gastric cancer. The hope is that these studies may facilitate the development of clinical trials to explore therapies in defined sets of patients, ultimately improving survival from this deadly disease.

Published
2018

18. Supplementary Figure 1 from IGKV3 Proteins as Candidate “Off-the-Shelf” Vaccines for Kappa-Light Chain–Restricted B-Cell Non-Hodgkin Lymphomas

Author

Martorelli, Debora, primary, Guidoboni, Massimo, primary, De Re, Valli, primary, Muraro, Elena, primary, Turrini, Riccardo, primary, Merlo, Anna, primary, Pasini, Elisa, primary, Caggiari, Laura, primary, Romagnoli, Luca, primary, Spina, Michele, primary, Mortarini, Roberta, primary, Gasparotto, Daniela, primary, Mazzucato, Mario, primary, Carbone, Antonino, primary, Rosato, Antonio, primary, Anichini, Andrea, primary, and Dolcetti, Riccardo, primary

Published
2023
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19. Supplementary Figure Legend and Tables 1 - 5 from IGKV3 Proteins as Candidate “Off-the-Shelf” Vaccines for Kappa-Light Chain–Restricted B-Cell Non-Hodgkin Lymphomas

Author

Martorelli, Debora, primary, Guidoboni, Massimo, primary, De Re, Valli, primary, Muraro, Elena, primary, Turrini, Riccardo, primary, Merlo, Anna, primary, Pasini, Elisa, primary, Caggiari, Laura, primary, Romagnoli, Luca, primary, Spina, Michele, primary, Mortarini, Roberta, primary, Gasparotto, Daniela, primary, Mazzucato, Mario, primary, Carbone, Antonino, primary, Rosato, Antonio, primary, Anichini, Andrea, primary, and Dolcetti, Riccardo, primary

Published
2023
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20. Supplementary Figure 2 from IGKV3 Proteins as Candidate “Off-the-Shelf” Vaccines for Kappa-Light Chain–Restricted B-Cell Non-Hodgkin Lymphomas

Author

Martorelli, Debora, primary, Guidoboni, Massimo, primary, De Re, Valli, primary, Muraro, Elena, primary, Turrini, Riccardo, primary, Merlo, Anna, primary, Pasini, Elisa, primary, Caggiari, Laura, primary, Romagnoli, Luca, primary, Spina, Michele, primary, Mortarini, Roberta, primary, Gasparotto, Daniela, primary, Mazzucato, Mario, primary, Carbone, Antonino, primary, Rosato, Antonio, primary, Anichini, Andrea, primary, and Dolcetti, Riccardo, primary

Published
2023
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27. Prospective Evaluation of Different Methods for Volumetric Analysis on [18F]FDG PET/CT in Pediatric Hodgkin Lymphoma

Author

Lopci, Egesta, primary, Elia, Caterina, additional, Catalfamo, Barbara, additional, Burnelli, Roberta, additional, De Re, Valli, additional, Mussolin, Lara, additional, Piccardo, Arnoldo, additional, Cistaro, Angelina, additional, Borsatti, Eugenio, additional, Zucchetta, Pietro, additional, Bianchi, Maurizio, additional, Buffardi, Salvatore, additional, Farruggia, Piero, additional, Garaventa, Alberto, additional, Sala, Alessandra, additional, Vinti, Luciana, additional, Mauz-Koerholz, Christine, additional, and Mascarin, Maurizio, additional

Published
2022
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28. Quantitative Plasma Proteomics to Identify Candidate Biomarkers of Relapse in Pediatric/Adolescent Hodgkin Lymphoma

Author

Repetto, Ombretta, primary, Caggiari, Laura, additional, De Zorzi, Mariangela, additional, Elia, Caterina, additional, Mussolin, Lara, additional, Buffardi, Salvatore, additional, Pillon, Marta, additional, Muggeo, Paola, additional, Casini, Tommaso, additional, Steffan, Agostino, additional, Mauz-Körholz, Christine, additional, Mascarin, Maurizio, additional, and De Re, Valli, additional

Published
2022
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33. HER2–CDH1 Interaction via Wnt/B-Catenin Is Associated with Patients’ Survival in HER2-Positive Metastatic Gastric Adenocarcinoma

Author

De Re, Valli, primary, Alessandrini, Lara, additional, Brisotto, Giulia, additional, Caggiari, Laura, additional, De Zorzi, Mariangela, additional, Casarotto, Mariateresa, additional, Miolo, Gianmaria, additional, Puglisi, Fabio, additional, Garattini, Silvio Ken, additional, Lonardi, Sara, additional, Cannizzaro, Renato, additional, Canzonieri, Vincenzo, additional, Fassan, Matteo, additional, and Steffan, Agostino, additional

Published
2022
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38. Prospective Evaluation of Different Methods for Volumetric Analysis on [ 18 F]FDG PET/CT in Pediatric Hodgkin Lymphoma.

Author

Lopci, Egesta, Elia, Caterina, Catalfamo, Barbara, Burnelli, Roberta, De Re, Valli, Mussolin, Lara, Piccardo, Arnoldo, Cistaro, Angelina, Borsatti, Eugenio, Zucchetta, Pietro, Bianchi, Maurizio, Buffardi, Salvatore, Farruggia, Piero, Garaventa, Alberto, Sala, Alessandra, Vinti, Luciana, Mauz-Koerholz, Christine, and Mascarin, Maurizio

Subjects
VOLUMETRIC analysis, CHILDHOOD cancer, HODGKIN'S disease, EVALUATION methodology, ABSOLUTE value
Abstract

Rationale: Therapy response evaluation by 18F-fluorodeoxyglucose PET/CT (FDG PET) has become a powerful tool for the discrimination of responders from non-responders in pediatric Hodgkin lymphoma (HL). Recently, volumetric analyses have been regarded as a valuable tool for disease prognostication and biological characterization in cancer. Given the multitude of methods available for volumetric analysis in HL, the AIEOP Hodgkin Lymphoma Study Group has designed a prospective analysis of the Italian cohort enrolled in the EuroNet-PHL-C2 trial. Methods: Primarily, the study aimed to compare the different segmentation techniques used for volumetric assessment in HL patients at baseline (PET1) and during therapy: early (PET2) and late assessment (PET3). Overall, 50 patients and 150 scans were investigated for the current analysis. A dedicated software was used to semi-automatically delineate contours of the lesions by using different threshold methods. More specifically, four methods were applied: (1) fixed 41% threshold of the maximum standardized uptake value (SUVmax) within the respective lymphoma site (V41%), (2) fixed absolute SUV threshold of 2.5 (V2.5); (3) SUVmax(lesion)/SUVmean liver >1.5 (Vliver); (4) adaptive method (AM). All parameters obtained from the different methods were analyzed with respect to response. Results: Among the different methods investigated, the strongest correlation was observed between AM and Vliver (rho > 0.9; p < 0.001 for SUVmean, MTV and TLG at all scan timing), along with V2.5 and AM or Vliver (rho 0.98, p < 0.001 for TLG at baseline; rho > 0.9; p < 0.001 for SUVmean, MTV and TLG at PET2 and PET3, respectively). To determine the best segmentation method, we applied logistic regression and correlated different results with Deauville scores at late evaluation. Logistic regression demonstrated that MTV (metabolic tumor volume) and TLG (total lesion glycolysis) computation according to V2.5 and Vliver significantly correlated to response to treatment (p = 0.01 and 0.04 for MTV and 0.03 and 0.04 for TLG, respectively). SUVmean also resulted in significant correlation as absolute value or variation. Conclusions: The best correlation for volumetric analysis was documented for AM and Vliver, followed by V2.5. The volumetric analyses obtained from V2.5 and Vliver significantly correlated to response to therapy, proving to be preferred thresholds in our pediatric HL cohort. [ABSTRACT FROM AUTHOR]

Published
2022
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44. Second-line treatments for Advanced Hepatocellular Carcinoma: A Systematic Review and Bayesian Network Meta-analysis

Author

Solimando, Antonio Giovanni, primary, Susca, Nicola, additional, Argentiero, Antonella, additional, Brunetti, Oronzo, additional, Leone, Patrizia, additional, De Re, Valli, additional, Fasano, Rossella, additional, Krebs, Markus, additional, Petracci, Elisabetta, additional, Azzali, Irene, additional, Nanni, Oriana, additional, Silvestris, Nicola, additional, Vacca, Angelo, additional, and Racanelli, Vito, additional

Published
2021
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45. Proteomic Exploration of Plasma Exosomes and Other Small Extracellular Vesicles in Pediatric Hodgkin Lymphoma: A Potential Source of Biomarkers for Relapse Occurrence

Author

Repetto, Ombretta, primary, Lovisa, Federica, additional, Elia, Caterina, additional, Enderle, Daniel, additional, Romanato, Filippo, additional, Buffardi, Salvatore, additional, Sala, Alessandra, additional, Pillon, Marta, additional, Steffan, Agostino, additional, Burnelli, Roberta, additional, Mussolin, Lara, additional, Mascarin, Maurizio, additional, and De Re, Valli, additional

Published
2021
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