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2. Predictive Value of CD8 Expression and FoxP3 Methylation in Nasopharyngeal Carcinoma Patients Treated with Chemoradiotherapy in a Non-endemic Area

Author

Muraro, E., Vaccher, E., Furlan, C., Fratta, E., Fanetti, G., Fae’, D. A., Martorelli, D., Cangemi, M., Polesel, J., Navarria, F., Gobitti, C., Comaro, E., Scaini, C., Pratesi, C., Zanussi, S., Lupato, V., Grando, G., Giacomarra, V., Sulfaro, S., Barzan, L., Dolcetti, R., Steffan, A., Canzonieri, V., and Franchin, G.

Published
2020
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3. Genomic instability analysis in DNA from Papanicolaou test provides proof-of-principle early diagnosis of high-grade serous ovarian cancer

Author

Paracchini, L, Mannarino, L, Romualdi, C, Zadro, R, Beltrame, L, Nerini, I, Zola, P, Laudani, M, Pagano, E, Giordano, L, Fruscio, R, Landoni, F, Franceschi, S, Dalessandro, M, Canzonieri, V, Bocciolone, L, Lorusso, D, Bosetti, C, Raspagliesi, F, Garassino, I, D'Incalci, M, Marchini, S, Grassi, T, Bianchi, T, Cursano, G, Mangili, G, Scambia, G, Marchetti, C, Boldorini, R, De Rosa, G, Ferrero, A, Feyles, E, Goia, M, Manini, C, Orlassino, R, Surico, D, Volante, M, Greggi, S, Jaconi, M, Bella, C, Vitobello, D, di Loreto, C, Pizzolitto, S, Zanconati, F, Ciccone, G, Armaroli, P, Larato, C, Rizzolo, R, Paracchini L., Mannarino L., Romualdi C., Zadro R., Beltrame L., Nerini I. F., Zola P., Laudani M. E., Pagano E., Giordano L., Fruscio R., Landoni F., Franceschi S., Dalessandro M. L., Canzonieri V., Bocciolone L., Lorusso D., Bosetti C., Raspagliesi F., Garassino I. M. G., D'Incalci M., Marchini S., Grassi T., Bianchi T., Cursano G., Mangili G., Scambia G., Marchetti C., Boldorini R., De Rosa G., Ferrero A., Feyles E., Goia M., Manini C., Orlassino R., Surico D., Volante M., Greggi S., Jaconi M., Bella C. D., Vitobello D., di Loreto C., Pizzolitto S., Zanconati F., Ciccone G., Armaroli P., Larato C., Rizzolo R., Paracchini, L, Mannarino, L, Romualdi, C, Zadro, R, Beltrame, L, Nerini, I, Zola, P, Laudani, M, Pagano, E, Giordano, L, Fruscio, R, Landoni, F, Franceschi, S, Dalessandro, M, Canzonieri, V, Bocciolone, L, Lorusso, D, Bosetti, C, Raspagliesi, F, Garassino, I, D'Incalci, M, Marchini, S, Grassi, T, Bianchi, T, Cursano, G, Mangili, G, Scambia, G, Marchetti, C, Boldorini, R, De Rosa, G, Ferrero, A, Feyles, E, Goia, M, Manini, C, Orlassino, R, Surico, D, Volante, M, Greggi, S, Jaconi, M, Bella, C, Vitobello, D, di Loreto, C, Pizzolitto, S, Zanconati, F, Ciccone, G, Armaroli, P, Larato, C, Rizzolo, R, Paracchini L., Mannarino L., Romualdi C., Zadro R., Beltrame L., Nerini I. F., Zola P., Laudani M. E., Pagano E., Giordano L., Fruscio R., Landoni F., Franceschi S., Dalessandro M. L., Canzonieri V., Bocciolone L., Lorusso D., Bosetti C., Raspagliesi F., Garassino I. M. G., D'Incalci M., Marchini S., Grassi T., Bianchi T., Cursano G., Mangili G., Scambia G., Marchetti C., Boldorini R., De Rosa G., Ferrero A., Feyles E., Goia M., Manini C., Orlassino R., Surico D., Volante M., Greggi S., Jaconi M., Bella C. D., Vitobello D., di Loreto C., Pizzolitto S., Zanconati F., Ciccone G., Armaroli P., Larato C., and Rizzolo R.

Abstract

Late diagnosis and the lack of screening methods for early detection define high-grade serous ovarian cancer (HGSOC) as the gynecological malignancy with the highest mortality rate. In the work presented here, we investigated a retrospective and multicentric cohort of 250 archival Papanicolaou (Pap) test smears collected during routine gynecological screening. Samples were taken at different time points (from 1 month to 13.5 years before diagnosis) from 113 presymptomatic women who were subsequently diagnosed with HGSOC (pre-HGSOC) and from 77 healthy women. Genome instability was detected through low-pass whole-genome sequencing of DNA derived from Pap test samples in terms of copy number profile abnormality (CPA). CPA values of DNA extracted from Pap test samples from pre-HGSOC women were substantially higher than those in samples from healthy women. Consistently with the longitudinal analysis of clonal pathogenic TP53 mutations, this assay could detect HGSOC presence up to 9 years before diagnosis. This finding confirms the continual shedding of tumor cells from fimbriae toward the endocervical canal, suggesting a new path for the early diagnosis of HGSOC. We integrated the CPA score into the EVA (early ovarian cancer) test, the sensitivity of which was 75% (95% CI, 64.97 to 85.79), the specificity 96% (95% CI, 88.35 to 100.00), and the accuracy 81%. This proof-of-principle study indicates that the early diagnosis of HGSOC is feasible through the analysis of genomic alterations in DNA from endocervical smears.

Published
2023

5. Analysis of A Disintegrin and Metalloprotease 17 (ADAM17) Expression as a Prognostic Marker in Ovarian Cancer Patients Undergoing First-Line Treatment Plus Bevacizumab

Author

Fabbi, M, Costa, D, Russo, D, Arenare, L, Gaggero, G, Signoriello, S, Scambia, G, Pisano, C, Colombo, N, Losito, N, Filaci, G, Spina, A, Califano, D, Scognamiglio, G, Gadducci, A, Mezzanzanica, D, Bagnoli, M, Ferrini, S, Canzonieri, V, Chiodini, P, Perrone, F, Pignata, S, Fabbi M., Costa D., Russo D., Arenare L., Gaggero G., Signoriello S., Scambia G., Pisano C., Colombo N., Losito N. S., Filaci G., Spina A., Califano D., Scognamiglio G., Gadducci A., Mezzanzanica D., Bagnoli M., Ferrini S., Canzonieri V., Chiodini P., Perrone F., Pignata S., Fabbi, M, Costa, D, Russo, D, Arenare, L, Gaggero, G, Signoriello, S, Scambia, G, Pisano, C, Colombo, N, Losito, N, Filaci, G, Spina, A, Califano, D, Scognamiglio, G, Gadducci, A, Mezzanzanica, D, Bagnoli, M, Ferrini, S, Canzonieri, V, Chiodini, P, Perrone, F, Pignata, S, Fabbi M., Costa D., Russo D., Arenare L., Gaggero G., Signoriello S., Scambia G., Pisano C., Colombo N., Losito N. S., Filaci G., Spina A., Califano D., Scognamiglio G., Gadducci A., Mezzanzanica D., Bagnoli M., Ferrini S., Canzonieri V., Chiodini P., Perrone F., and Pignata S.

Abstract

To find prognostic factors for advanced ovarian cancer patients undergoing first-line therapy with carboplatin, paclitaxel and bevacizumab, we investigated the expression of a disintegrin and metalloprotease 17 (ADAM17) in cancer tissues. ADAM17 has been involved in ovarian cancer development, progression and cell resistance to cisplatin. Tissue microarrays from 309 ovarian cancer patients enrolled in the MITO16A/MANGO-OV2 clinical trial were analyzed by immunohistochemistry for ADAM17 protein expression. Intensity and extent of staining were combined into a semi-quantitative visual grading system (H score) which was related to clinicopathological characteristics of cases and the clinical outcome of patients by univariate and multivariate Cox regression models. ADAM17 immunostaining was detected in most samples, mainly localized in the tumor cells, with variable intensity across the cohort. Kaplan–Meier survival curves, generated according to the best cut-off value for the ADAM17 H score, showed that high ADAM17 expression was associated with worse prognosis for PFS and OS. However, after the application of a shrinkage procedure to adjust for overfitting hazard ratio estimates, the ADAM17 value as prognostic factor was lost. As subgroup analysis suggested that ADAM17 expression could be prognostically relevant in cases with no residual disease at baseline, further studies in this patient category may be worth planning.

Published
2022

6. OC.15.2 SMALL BOWEL CARCINOMAS MAY COMPLICATE COELIAC DISEASE DESPITE STRICT ADHERENCE TO GLUTEN-FREE DIET: A CASE SERIES FROM THE SMALL BOWEL CANCER ITALIAN CONSORTIUM

Author

Bianchi, P.I., primary, Vanoli, A., additional, Lenti, M., additional, Guerini, C., additional, Arpa, G., additional, Quaquarini, E., additional, Aronico, N., additional, Grillo, F., additional, Nesi, G., additional, Furlan, D., additional, Latella, G., additional, Sessa, F., additional, Mescoli, C., additional, Rugge, M., additional, Ferrero, S., additional, Macciomei, M., additional, Santini, D., additional, Volta, U., additional, De Giorgio, R., additional, Caio, G., additional, Calabro, A., additional, Ciacci, C., additional, D'Armiento, M., additional, Villanacci, V., additional, Cannizzaro, R., additional, Canzonieri, V., additional, Florena, A., additional, Ciardi, A., additional, Elli, L., additional, Vecchi, M., additional, Zingone, F., additional, Reggiani Bonetti, L., additional, Astegiano, M., additional, Sandri, G., additional, Silano, M., additional, Usai, P., additional, Perfetti, V., additional, Giannone, A., additional, Barresi, V., additional, Ciccocioppo, R., additional, Biletta, E., additional, Corazza, G., additional, and Di Sabatino, A., additional

Published
2023
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7. PC.01.9 HYPOMETHYLATION OF LINE-1 IN SMALL BOWEL CARCINOMAS AND COELIAC DISEASE

Author

Guerini, C., primary, Bianchi, P.I., additional, Libera, L., additional, Vanoli, A., additional, Arpa, G., additional, Aronico, N., additional, Furlan, D., additional, Grillo, F., additional, Nesi, G., additional, Sampietro, G., additional, Ardizzone, S., additional, Fociani, P., additional, Fiocca, R., additional, Latella, G., additional, Sessa, F., additional, D'Errico, A., additional, Malvi, D., additional, Mescoli, C., additional, Rugge, M., additional, Ferrero, S., additional, Poggioli, G., additional, Rizzello, F., additional, Macciomei, M., additional, Santini, D., additional, Volta, U., additional, De Giorgio, R., additional, Caio, G., additional, Calabro, A., additional, Ciacci, C., additional, D'Armiento, M., additional, Rizzo, A., additional, Solina, G., additional, Tonelli, F., additional, Villanacci, V., additional, Cannizzaro, R., additional, Canzonieri, V., additional, Florena, A., additional, Biancone, L., additional, Monteleone, G., additional, Caronna, R., additional, Ciardi, A., additional, Elli, L., additional, Caprioli, F., additional, Vecchi, M., additional, D'Inca, R., additional, Zingone, F., additional, D'Odorico, A., additional, Oreggia, B., additional, Reggiani Bonetti, L., additional, Astegiano, M., additional, Cantoro, L., additional, Papi, C., additional, Sandri, G., additional, Silano, M., additional, Usai, P., additional, Perfetti, V., additional, Quaquarini, E., additional, Giannone, A., additional, Orlandi, A., additional, Barresi, V., additional, Ciccocioppo, R., additional, Amodeo, G., additional, Biletta, E., additional, and Di Sabatino, A., additional

Published
2023
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8. Evaluation of angiogenesis-related genes as prognostic biomarkers of bevacizumab treated ovarian cancer patients: Results from the phase iv mito16a/mango ov-2 translational study

Author

Califano, D, Gallo, D, Vinciguerra, G, De Cecio, R, Arenare, L, Signoriello, S, Russo, D, Ferrandina, G, Citron, F, Losito, N, Gargiulo, P, Simeon, V, Scambia, G, Cecere, S, Montella, M, Colombo, N, Tognon, G, Bignotti, E, Zannoni, G, Canzonieri, V, Ciucci, A, Spina, A, Scognamiglio, G, Del Sesto, M, Schettino, C, Piccirillo, M, Perrone, F, Chiodini, P, Pignata, S, Baldassarre, G, Califano D., Gallo D., Vinciguerra G. L. R., De Cecio R., Arenare L., Signoriello S., Russo D., Ferrandina G., Citron F., Losito N. S., Gargiulo P., Simeon V., Scambia G., Cecere S. C., Montella M., Colombo N., Tognon G., Bignotti E., Zannoni G. F., Canzonieri V., Ciucci A., Spina A., Scognamiglio G., Del Sesto M., Schettino C., Piccirillo M. C., Perrone F., Chiodini P., Pignata S., Baldassarre G., Califano, D, Gallo, D, Vinciguerra, G, De Cecio, R, Arenare, L, Signoriello, S, Russo, D, Ferrandina, G, Citron, F, Losito, N, Gargiulo, P, Simeon, V, Scambia, G, Cecere, S, Montella, M, Colombo, N, Tognon, G, Bignotti, E, Zannoni, G, Canzonieri, V, Ciucci, A, Spina, A, Scognamiglio, G, Del Sesto, M, Schettino, C, Piccirillo, M, Perrone, F, Chiodini, P, Pignata, S, Baldassarre, G, Califano D., Gallo D., Vinciguerra G. L. R., De Cecio R., Arenare L., Signoriello S., Russo D., Ferrandina G., Citron F., Losito N. S., Gargiulo P., Simeon V., Scambia G., Cecere S. C., Montella M., Colombo N., Tognon G., Bignotti E., Zannoni G. F., Canzonieri V., Ciucci A., Spina A., Scognamiglio G., Del Sesto M., Schettino C., Piccirillo M. C., Perrone F., Chiodini P., Pignata S., and Baldassarre G.

Abstract

Background. Epithelial ovarian cancer (EOC) is a rare, highly lethal disease. In a subset of high grade EOC patients, maintenance therapy with the antiangiogenic drug Bevacizumab (BEV) is a valuable option. To date, no validated predictive or prognostic biomarkers exist for selecting EOC patients that might benefit from BEV treatment. Methods. Immunohistochemistry and RT-qPCR evaluated the expression of seven angiogenesis-related proteins and of a twelve microRNAs angio-signature in EOC patients, treated in first line with chemotherapy plus BEV (MITO16A/ManGO OV-2 phase IV trial). Centralized statistical analyses assessed the associations between each biomarker, clinical prognostic factors and survival outcomes. Results. High miR-484 expression was associated with longer progression-free and overall survival. Notably, the combined expression of miR-484 and its target VEGFB identified a subset of patients that might mostly benefit from BEV treatment. No other significant correlations were found between the other analyzed biomarkers and patients’ survival. The application of a shrinkage procedure to adjust for over-fitting hazard ratio estimates reduced the association significance. Conclusions. The analysis of angiogenesis related biomarkers in EOC patients homogenously treated with BEV in first line provides novel insight in their prognostic value and suggests that some of them might merit to be tested as predictive markers of drug activity in dedicated randomized trials.

Published
2021

10. A Green Synthesis of Carbene-Metal-Amides (CMAs) and Carboline-Derived CMAs with Potent in vitro and ex vivo Anticancer Activity

Author

Tzouras, N.V. Scattolin, T. Gobbo, A. Bhandary, S. Rizzolio, F. Cavarzerani, E. Canzonieri, V. Van Hecke, K. Vougioukalakis, G.C. Cazin, C.S.J. Nolan, S.P.

Abstract

The modularity and ease of synthesis of carbene-metal-amide (CMA) complexes based on the coinage metals (Au, Ag, Cu) and N-heterocyclic carbenes (NHCs) as ancillary ligands pave the way for the expansion of their applications beyond photochemistry and catalysis. Herein, we further improve the synthesis of such compounds by circumventing the use of toxic organic solvents which were previously required for their purification, and we expand their scope to include complexes incorporating carbolines as the amido fragments. The novel complexes are screened both in vitro and ex vivo, against several cancer cell lines and high-grade serous ovarian cancer (HGSOC) tumoroids, respectively. Excellent cytotoxicity values are obtained for most complexes, while the structural variety of the CMA library screened thus far, provides promising leads for future developments. Variations of all three components (NHC, metal, amido ligand), enable the establishment of trends regarding cytotoxicity and selectivity towards cancerous over normal cells. © 2022 Wiley-VCH GmbH.

Published
2022

12. P301 Non-familial small bowel carcinomas in Crohnʼs disease: clinico-pathological, molecular and prognostic features

Author

Di Sabatino, A., Vanoli, A., Furlan, D., Giuffrida, P., Klersy, C., Grillo, F., Fiocca, R., Mescoli, C., Rugge, M., Nesi, G., Fociani, P., Sampietro, G., Ardizzone, S., Luinetti, O., Calabrò, A., Tonelli, F., Volta, U., Santini, D., Caio, G., Elli, L., Ferrero, S., Latella, G., Ciardi, A., Solina, G., Rizzo, A., Ciacci, C., DʼArmiento, F.P., Salemme, M., Villanacci, V., Cannizzaro, R., Canzonieri, V., Reggiani Bonetti, L., Biancone, L., Monteleone, G., Orlandi, A., Santeusanio, G., Macciomei, M.C., DʼIncà, R., Perfetti, V., Sandri, G., Silano, M., Florena, A.M., Giannone, A.G., Papi, C., Coppola, L., Usai, P., Maccioni, A., Astegiano, M., Migliora, P., Manca, R., Martino, M., Trapani, D., Cerutti, R., Alberizzi, P., Riboni, R., Sessa, F., Paulli, M., Solcia, E., and Corazza, G.R.

Published
2017
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13. Epstein-Barr virus BART microRNAs in EBV- associated Hodgkin lymphoma and gastric cancer

Author

De Re, V., Caggiari, L., De Zorzi, M., Fanotto, V., Miolo, G., Puglisi, F., Cannizzaro, R., Canzonieri, V., Steffan, A., Farruggia, P., Lopci, E., D'Amore, E. S. G., Burnelli, R., Mussolin, L., Mascarin, M., De Re, V., Caggiari, L., De Zorzi, M., Fanotto, V., Miolo, G., Puglisi, F., Cannizzaro, R., Canzonieri, V., Steffan, A., Farruggia, P., Lopci, E., D'Amore, E. S. G., Burnelli, R., Mussolin, L., and Mascarin, M.

Subjects
Cancer Research, Cell type, Micro RNA, Epidemiology, HL, Review, medicine.disease_cause, Gastric carcinoma cancer, lcsh:RC254-282, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, Immune system, EBV, hemic and lymphatic diseases, microRNA, Hodgkin lymphoma, GC, Medicine, Epstein-Barr virus, lcsh:RC109-216, 030304 developmental biology, miRNA, 0303 health sciences, Tumor microenvironment, BamHI fragment a rightward transcript, business.industry, Autophagy, Cancer, Epstein-Barr viru, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Epstein–Barr virus, Microvesicles, Infectious Diseases, Oncology, 030220 oncology & carcinogenesis, Cancer research, BART, business
Abstract

Background EBV produces miRNAs with important functions in cancer growth, tumor invasion and host immune surveillance. The discovery of EBV miR-BARTs is recent, and most of their functions are still unknown. Nonetheless, some new studies underline their key roles in EBV-associated malignancies. Main body In EBV-associated tumors, the expression profile of miR-BARTs varies according to the cell type, autophagic process and signals received from the tumor microenvironment. By the same way of interest is the interaction between tumor cells and the tumor environment by the release of selected EBV miR-BARTs in addition to the tumor proteins trough tumor exosomes. Conclusion In this review, we discuss new findings regarding EBV miR-BARTs in Hodgkin lymphoma and gastric cancer. The recent discovery that miRNAs are released by exosomes, including miR-BARTs, highlights the importance of tumor and microenvironment interplay with more specific effects on the host immune response.

Published
2020

15. Upconversion-mediated Boltzmann thermometry in double-layered Bi2SiO5:Yb3+,Tm3+@SiO2 hollow nanoparticles

Author

Casagrande, E., Back, M., Cristofori, D., Ueda, J., Tanabe, S., Palazzolo, S., Rizzolio, F., Canzonieri, V., Trave, E., and Riello, P.

Subjects
Thermal equilibrium, Materials science, Band gap, business.industry, Settore FIS/01 - Fisica Sperimentale, Settore CHIM/07 - Fondamenti Chimici delle Tecnologie, Nanoparticle, General Chemistry, Atmospheric temperature range, Photon upconversion, Boltzmann distribution, Thermalisation, Excited state, Materials Chemistry, Optoelectronics, business, Settore CHIM/02 - Chimica Fisica
Abstract

Ratiometric optical thermometry is one of the most promising techniques for contactless temperature sensing. However, despite the efforts devoted in the last decades, the development of nanothermometers characterized by high reliability along with suitable sensitivity (Sr > 1% K−1) and thermal resolution (δT < 0.5 K) in the physiological temperature range is still a critical challenge in the biological field. Here, we propose uniform Yb,Tm co-doped crystalline Bi2SiO5@SiO2 hollow upconverting nanoparticles as red-NIR emitting nanophosphors for ratiometric optical thermometry. The synthetic procedure leads to double-layered Bi2SiO5:Yb,Tm@SiO2 hollow nanoparticles. The thermometric performances are investigated in a wide temperature range (80–800 K) demonstrating the reliability of the thermometer based on the emission ratio between the 1G4 → 3F4 (∼650 nm) and 3F2,3 → 3H6 (∼700 nm) transitions. Despite the impossibility to be in thermal equilibrium due to the large energy gap between 1G4 and 3F2,3 excited states, their relative populations are demonstrated to follow the Boltzmann distribution, reflecting, through the upconversion processes, the thermalization between the 3F2,3 and 3H4 excited states. Consequently, the system features high thermal sensitivity (Sr = 1.95% K−1 at 300 K) and excellent thermal resolution (0.28 K at 300 K) for a highly reliable system following the Boltzmann-distribution. In addition, the superior performances of the investigated system in comparison with other NIR-to-NIR thermometers such as Nd3+-based ones and the biocompatibility of the NPs prove its potential in the physiological temperature range.

Published
2020
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16. Probe-based confocal laser endomicroscopy (pCLE) is a suitable method for extrapulmonary high grade neuroendocrine rectal carcinoma (HGNEC) evaluation

Author

Cannizzaro R, Maiero S, Fornasarig M, Canzonieri V, Magris R, Guarnieri G, Urbani M, Buonadonna A, Baresic T, and Spessotto P

Subjects
neoangiogenesis, Probe-based confocal endomicroscopy, poorly differentiated adenocarcinoma, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, extrapulmonary high grade neuroendocrine carcinoma
Abstract

Renato Cannizzaro,1 Stefania Maiero,1 Mara Fornasarig,1 Vincenzo Canzonieri,2 Raffaella Magris,1 Giovanni Guarnieri,1 Martina Urbani,3 Angela Buonadonna,4 Tanja Baresic,5 Paola Spessotto61Oncological Gastroenterology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy; 2Pathology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy; 3Oncologic Radiation Therapy and Diagnostic Imaging, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy; 4Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy; 5Nuclear Medicine, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy; 6Molecular Oncology, Department of Translational Research, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, ItalyAbstract: The potential role of the probe-based confocal laser endomicroscopy (pCLE) has been analyzed in different pathologic conditions of the gastrointestinal tract. Here, we analyzed a case of extrapulmonary high grade neuroendocrine rectal carcinoma (HGNEC) using, for the first time, the pCLE system. A 72-year old man was diagnosed with an 8 cm diameter rectal HGNEC by standard colonoscopy integrated with the pCLE system. The diagnosis of neuroendocrine carcinoma was confirmed by immunohistochemical analyses. By using the pCLE system, we well defined and resolved vascular structures and mucosal architecture. An altered mucosal pattern and vascular defects, peculiar for HGNEC, were observed at high magnification, allowing the identification of a pattern which was quite different from that observed in poorly differentiated adenocarcinomas (PDA) where tissues appear darker, very irregular, even if glandular structures can still be recognized. This underlines the usefulness of pCLE in discriminating HGNECs from PDAs. In conclusion, pCLE could represent a valid and helpful method for in vivo HGNEC diagnosis, allowing prompt and careful management of the patient.Keywords: probe-based confocal endomicroscopy, neoangiogenesis, extrapulmonary high grade neuroendocrine carcinoma, poorly differentiated adenocarcinoma

Published
2019

18. 800P Tailoring adjuvant treatments in high-risk early stage endometrial cancer: Clinical outcomes of sequential chemoradiation in a real-word scenario

Author

de Scordilli, M., primary, Bartoletti, M., additional, Palazzari, E., additional, Mazzeo, R., additional, Michelotti, A., additional, Alberti, M., additional, Gerratana, L., additional, Nicoloso, M.S., additional, Corsetti, S., additional, Scalone, S., additional, Gigante, M., additional, Forte, S., additional, Clemente, N., additional, Del Fabro, A., additional, Lucia, E., additional, Ganis, A., additional, Giorda, G., additional, Canzonieri, V., additional, Sorio, R., additional, and Puglisi, F., additional

Published
2021
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22. Palladium(II)-η3-Allyl Complexes Bearing N-Trifluoromethyl N-Heterocyclic Carbenes: A New Generation of Anticancer Agents that Restrain the Growth of High-Grade Serous Ovarian Cancer Tumoroids

Author

Scattolin, T., Bortolamiol, E., Visentin, F., Palazzolo, S., Caligiuri, I., Perin, T., Canzonieri, V., Demitri, N., Rizzolio, F., Togni, A., Scattolin, T., Bortolamiol, E., Visentin, F., Palazzolo, S., Caligiuri, I., Perin, T., Canzonieri, V., Demitri, N., Rizzolio, F., and Togni, A.

Subjects
organoid, palladium allyl complexe, Ligand, Antineoplastic Agents, Ligands, Cell Line, palladium allyl complexes, Antineoplastic Agent, Coordination Complexes, Cell Line, Tumor, Humans, allylation, organoids, Cell Proliferation, Settore CHIM/03 - Chimica Generale e Inorganica, Ovarian Neoplasms, N-trifluoromethyl N-heterocyclic carbenes, Tumor, N-trifluoromethyl N-heterocyclic carbene, Coordination Complexe, Ovarian Neoplasm, ovarian cancer, Cisplatin, Female, Palladium, Human
Abstract

The first palladium organometallic compounds bearing N-trifluoromethyl N-heterocyclic carbenes have been synthesized. These η3-allyl complexes are potent antiproliferative agents against different cancer lines (for the most part, IC50 values fall in the range 0.02–0.5 μm). By choosing 1,3,5-triaza-7-phosphaadamantane (PTA) as co-ligand, we can improve the selectivity toward tumor cells, whereas the introduction of 2-methyl substituents generally reduces the antitumor activity slightly. A series of biochemical assays, aimed at defining the cellular targets of these palladium complexes, has shown that mitochondria are damaged before DNA, thus revealing a behavior substantially different from that of cisplatin and its derivatives. We assume that the specific mechanism of action of these organometallic compounds involves nucleophilic attack on the η3-allyl fragment. The effectiveness of a representative complex, 4 c, was verified on ovarian cancer tumoroids derived from patients. The results are promising: unlike carboplatin, our compound turned out to be very active and showed a low toxicity toward normal liver organoids.

Published
2020

23. PROGNOSTIC CORRELATION OF CELL-OF-ORIGIN AND MYC, BCL-2 AND BCL-6 STATUS IN HIV-ASSOCIATED DIFFUSE LARGE B-CELL LYMPHOMAS

Author

Rusconi, C, Crucitti, L, Re, A, Bandiera, L, Spina, M, Gini, G, Paulli, M, Lucioni, M, Facchetti, F, Goteri, G, Canzonieri, V, Lorenzi, L, Balzarini, P, Fisogni, S, Riboni, R, Malfitano, A, Bonfichi, M, Moioli, M, Nichelatti, M, Melle, F, Motta, G, Pileri, S, Cairoli, R, Rusconi C, Crucitti L, Re A, Bandiera L, Spina M, Gini G, Paulli M, Lucioni M, Facchetti F, Goteri G, Canzonieri V, Lorenzi L, Balzarini P, Fisogni S, Riboni R, Malfitano A, Bonfichi M, Moioli MC, Nichelatti M, Melle F, Motta G, Pileri SA, Cairoli R, Rusconi, C, Crucitti, L, Re, A, Bandiera, L, Spina, M, Gini, G, Paulli, M, Lucioni, M, Facchetti, F, Goteri, G, Canzonieri, V, Lorenzi, L, Balzarini, P, Fisogni, S, Riboni, R, Malfitano, A, Bonfichi, M, Moioli, M, Nichelatti, M, Melle, F, Motta, G, Pileri, S, Cairoli, R, Rusconi C, Crucitti L, Re A, Bandiera L, Spina M, Gini G, Paulli M, Lucioni M, Facchetti F, Goteri G, Canzonieri V, Lorenzi L, Balzarini P, Fisogni S, Riboni R, Malfitano A, Bonfichi M, Moioli MC, Nichelatti M, Melle F, Motta G, Pileri SA, and Cairoli R

Published
2019

24. Correction to: Long-Term Outcomes of Local Excision Following Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer (Annals of Surgical Oncology, (2021), 28, 5, (2801-2808), 10.1245/s10434-020-09243-6)

Author

D'Alimonte, L., Bao, Q. R., Spolverato, G., Capelli, Giovanni, Del Bianco, P., Albertoni, L., De Paoli, A., Guerrieri, M., Mantello, G., Gambacorta, Maria Antonietta, Canzonieri, V., Valentini, Vincenzo, Coco, Claudio, and Pucciarelli, S.

Subjects
N/A, Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA
Published
2021

26. OC-0623 SMAD3 expression and genetic variation could predict response to chemoradiation in rectal cancer

Author

Palazzari, E., primary, Cecchin, E., additional, De Mattia, E., additional, Polesel, J., additional, Innocente, R., additional, Navarria, F., additional, Belluco, C., additional, Lauretta, A., additional, Canzonieri, V., additional, Buonadonna, A., additional, Spolverato, G., additional, Pucciarelli, S., additional, Franchin, G., additional, Toffoli, G., additional, and De Paoli, A., additional

Published
2021
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27. GENETIC AND PHENOTYPIC ATTRIBUTES OF SPLENIC MARGINAL ZONE LYMPHOMA

Author

Bonfiglio, F., primary, Bruscaggin, A., additional, Guidetti, F., additional, Terzi di Bergamo, L., additional, Faderl, M., additional, Spina, V., additional, Condoluci, A., additional, Bonomini, L., additional, Forestieri, G., additional, Koch, R., additional, Piffaretti, D., additional, Pini, K., additional, Pirosa, M. C., additional, Cittone, M. G., additional, Arribas, A., additional, Lucioni, M., additional, Ghilardi, G., additional, Wu, W., additional, Arcaini, L., additional, Baptista, M. J., additional, Bastidas, G., additional, Bea, S., additional, Boldorini, R., additional, Broccoli, A., additional, Canzonieri, V., additional, Cascione, L., additional, Ceriani, L., additional, Cogliatti, S., additional, Derenzini, E., additional, Devizzi, L., additional, Dietrich, S., additional, Elia, A. R., additional, Facchetti, F., additional, Gaidano, G., additional, Garcia, J. F., additional, Gerber, B., additional, Ghia, P., additional, Silva, M. G., additional, Gritti, G., additional, Guidetti, A., additional, Hitz, F., additional, Inghirami, G., additional, Ladetto, M., additional, Lopez‐Guillermo, A., additional, Lucchini, E., additional, Maiorana, A., additional, Marasca, R., additional, Matutes, E., additional, Meignin, V., additional, Merli, M., additional, Moccia, A., additional, Mollejo, M., additional, Montalban, C., additional, Novak, U., additional, Oscier, D. G., additional, Passamonti, F., additional, Piazza, F., additional, Pizzolitto, S., additional, Sabattini, E., additional, Salles, G., additional, Santambrogio, E., additional, Scarfó, L., additional, Stathis, A., additional, Stüssi, G., additional, Geyer, J. T., additional, Tapia, G., additional, Thieblemont, C., additional, Tousseyn, T., additional, Tucci, A., additional, Visco, C., additional, Vitolo, U., additional, Zenz, T., additional, Zinzani, P. L., additional, Khiabanian, H., additional, Calcinotto, A., additional, Bertoni, F., additional, Bhagat, G., additional, Campo, E., additional, Leval, L., additional, Dirnhofer, S., additional, Pileri, S. A., additional, Piris, M. Án., additional, Traverse‐Glehen, A., additional, Tzankov, A., additional, Paulli, M., additional, Ponzoni, M., additional, Mazzucchelli, L., additional, Cavalli, F., additional, Zucca, E., additional, and Rossi, D., additional

Published
2021
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28. Long-Term Outcomes of Local Excision Following Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

Author

D'Alimonte, L., Bao, Q. R., Spolverato, G., Capelli, Giovanni, Del Bianco, P., Albertoni, L., De Paoli, A., Guerrieri, M., Mantello, G., Gambacorta, Maria Antonietta, Canzonieri, V., Valentini, Vincenzo, Coco, Claudio, Pucciarelli, S., Capelli G., Gambacorta M. A. (ORCID:0000-0001-5455-8737), Valentini V. (ORCID:0000-0003-4637-6487), Coco C. (ORCID:0000-0002-4713-7093), D'Alimonte, L., Bao, Q. R., Spolverato, G., Capelli, Giovanni, Del Bianco, P., Albertoni, L., De Paoli, A., Guerrieri, M., Mantello, G., Gambacorta, Maria Antonietta, Canzonieri, V., Valentini, Vincenzo, Coco, Claudio, Pucciarelli, S., Capelli G., Gambacorta M. A. (ORCID:0000-0001-5455-8737), Valentini V. (ORCID:0000-0003-4637-6487), and Coco C. (ORCID:0000-0002-4713-7093)

Abstract

Background: Local excision might represent an alternative to total mesorectal excision for patients with locally advanced rectal cancer who achieve a major or complete clinical response after neoadjuvant chemoradiotherapy. Methods: Between August 2005 and July 2011, 63 patients with mid-low rectal adenocarcinoma who had a major/complete clinical response after neoadjuvant chemoradiotherapy were enrolled in a multicenter prospective phase 2 trial and underwent transanal full thickness local excision. The main endpoint of this study was to evaluate the 5- and 10-year overall, relapse-free, local, and distant relapse-free survival, which were calculated by applying the Kaplan–Meier method. The rate of patients with rectum preserved and without stoma were also calculated. Results: Of 63 patients, 38 (60%) were male and 25 (40%) were female, with a median (range) age of 64 (25–82) years. At baseline, the following clinical stages were found: cT2, n = 21 (33.3%); cT3, n = 42 (66.6%), 39 (61.9%) patients were cN+. At a median (range) follow-up of 108 (32–166) months, the estimated cumulative 5- and 10-year overall survival, relapse-free survival, local recurrence-free survival, and distant recurrence-free survival were 87% (95% CI 76–93) and 79% (95% CI 66–87), 89% (95% CI 78–94) and 82% (95% CI 66–91), both 91% (95% CI 81–96), and 90% (95% CI 80–95) and 86% (95% CI 73–93), respectively. Overall, 49 (77.8%) patients had their rectum preserved, and 54 (84.1%) were stoma-free. Conclusion: In highly selected patients, the local excision approach after neoadjuvant chemoradiotherapy is associated with excellent long-term outcomes, high rates of rectum preservation and absence of permanent stoma.

Published
2021

29. Evaluation of angiogenesis-related genes as prognostic biomarkers of bevacizumab treated ovarian cancer patients: Results from the phase iv mito16a/mango ov-2 translational study

Author

Califano, D., Gallo, D., Vinciguerra, G. L. R., De Cecio, R., Arenare, L., Signoriello, S., Russo, D., Ferrandina, Maria Gabriella, Citron, F., Losito, N. S., Gargiulo, P., Simeon, V., Scambia, Giovanni, Cecere, S. C., Montella, M., Colombo, N., Tognon, G., Bignotti, E., Zannoni, Gian Franco, Canzonieri, V., Ciucci, A., Spina, A., Scognamiglio, G., Del Sesto, M., Schettino, C., Piccirillo, M. C., Perrone, F., Chiodini, Paola Maddalena, Pignata, S., Baldassarre, Gaetano, Ferrandina G. (ORCID:0000-0003-4672-4197), Scambia G. (ORCID:0000-0003-2758-1063), Zannoni G. F. (ORCID:0000-0003-1809-129X), Chiodini P., Baldassarre G., Califano, D., Gallo, D., Vinciguerra, G. L. R., De Cecio, R., Arenare, L., Signoriello, S., Russo, D., Ferrandina, Maria Gabriella, Citron, F., Losito, N. S., Gargiulo, P., Simeon, V., Scambia, Giovanni, Cecere, S. C., Montella, M., Colombo, N., Tognon, G., Bignotti, E., Zannoni, Gian Franco, Canzonieri, V., Ciucci, A., Spina, A., Scognamiglio, G., Del Sesto, M., Schettino, C., Piccirillo, M. C., Perrone, F., Chiodini, Paola Maddalena, Pignata, S., Baldassarre, Gaetano, Ferrandina G. (ORCID:0000-0003-4672-4197), Scambia G. (ORCID:0000-0003-2758-1063), Zannoni G. F. (ORCID:0000-0003-1809-129X), Chiodini P., and Baldassarre G.

Abstract

Background. Epithelial ovarian cancer (EOC) is a rare, highly lethal disease. In a subset of high grade EOC patients, maintenance therapy with the antiangiogenic drug Bevacizumab (BEV) is a valuable option. To date, no validated predictive or prognostic biomarkers exist for selecting EOC patients that might benefit from BEV treatment. Methods. Immunohistochemistry and RT-qPCR evaluated the expression of seven angiogenesis-related proteins and of a twelve microRNAs angio-signature in EOC patients, treated in first line with chemotherapy plus BEV (MITO16A/ManGO OV-2 phase IV trial). Centralized statistical analyses assessed the associations between each biomarker, clinical prognostic factors and survival outcomes. Results. High miR-484 expression was associated with longer progression-free and overall survival. Notably, the combined expression of miR-484 and its target VEGFB identified a subset of patients that might mostly benefit from BEV treatment. No other significant correlations were found between the other analyzed biomarkers and patients’ survival. The application of a shrinkage procedure to adjust for over-fitting hazard ratio estimates reduced the association significance. Conclusions. The analysis of angiogenesis related biomarkers in EOC patients homogenously treated with BEV in first line provides novel insight in their prognostic value and suggests that some of them might merit to be tested as predictive markers of drug activity in dedicated randomized trials.

Published
2021

36. PO-1112: Total neoadjuvant therapy in high risk rectal cancer: a feasibility pilot study

Author

Palazzari, E., primary, Buonadonna, A., additional, Lauretta, A., additional, Navarria, F., additional, Ongaro, E., additional, Foltran, L., additional, Innocente, R., additional, Belluco, C., additional, Ubiali, P., additional, Canzonieri, V., additional, Urbani, M., additional, Colombo, C., additional, Bertola, G., additional, and De Paoli, A., additional

Published
2020
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37. PROGNOSTIC CORRELATION OF CELL-OF-ORIGIN AND MYC, BCL-2 AND BCL-6 STATUS IN HIV-ASSOCIATED DIFFUSE LARGE B-CELL LYMPHOMAS

Author

Rusconi C, Crucitti L, Re A, Bandiera L, Spina M, Gini G, Paulli M, Lucioni M, Facchetti F, Goteri G, Canzonieri V, Lorenzi L, Balzarini P, Fisogni S, Riboni R, Malfitano A, Bonfichi M, Moioli MC, Nichelatti M, Melle F, Motta G, Pileri SA, Cairoli R, Rusconi, C, Crucitti, L, Re, A, Bandiera, L, Spina, M, Gini, G, Paulli, M, Lucioni, M, Facchetti, F, Goteri, G, Canzonieri, V, Lorenzi, L, Balzarini, P, Fisogni, S, Riboni, R, Malfitano, A, Bonfichi, M, Moioli, M, Nichelatti, M, Melle, F, Motta, G, Pileri, S, and Cairoli, R

Subjects
Hematology
Published
2019

39. Cell-of-Origin Identification and Prognostic Correlation in HIV-Associated Diffuse Large B-Cell Lymphomas: Results of an Italian Multicentric Study

Author

Rusconi, C, Re, A, Bandiera, L, Crucitti, L, Spina, M, Gini, G, Paulli, M, Lucioni, M, Facchetti, F, Goteri, G, Canzonieri, V, Lorenzi, L, Balzarini, P, Fisogni, S, Malfitano, A, Bonfichi, M, Moioli, M, Nichelatti, M, Melle, F, Motta, G, Pileri, S, Cairoli, R, Rusconi C, Re A, Bandiera L, Crucitti L, Spina M, Gini G, Paulli M, Lucioni M, Facchetti F, Goteri G, Canzonieri V, Lorenzi L, Balzarini P, Fisogni S, Malfitano A, Bonfichi M, Moioli MC, Nichelatti M, Melle F, Motta G, Pileri SA, Cairoli R, Rusconi, C, Re, A, Bandiera, L, Crucitti, L, Spina, M, Gini, G, Paulli, M, Lucioni, M, Facchetti, F, Goteri, G, Canzonieri, V, Lorenzi, L, Balzarini, P, Fisogni, S, Malfitano, A, Bonfichi, M, Moioli, M, Nichelatti, M, Melle, F, Motta, G, Pileri, S, Cairoli, R, Rusconi C, Re A, Bandiera L, Crucitti L, Spina M, Gini G, Paulli M, Lucioni M, Facchetti F, Goteri G, Canzonieri V, Lorenzi L, Balzarini P, Fisogni S, Malfitano A, Bonfichi M, Moioli MC, Nichelatti M, Melle F, Motta G, Pileri SA, and Cairoli R

Published
2018

41. Correction: PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability (Modern Pathology, (2020), 33, 7, (1398-1409), 10.1038/s41379-020-0497-0)

Author

Giuffrida, P., Arpa, G., Grillo, F., Klersy, C., Sampietro, G., Ardizzone, S., Fociani, P., Fiocca, R., Latella, G., Sessa, F., D'Errico, A., Malvi, D., Mescoli, C., Rugge, M., Nesi, G., Ferrero, S., Furlan, D., Poggioli, G., Rizzello, F., Macciomei, M. C., Santini, D., Volta, U., De Giorgio, R., Caio, G., Calabro, A., Ciacci, C., D'Armiento, M., Rizzo, A., Solina, G., Martino, M., Tonelli, F., Villanacci, V., Cannizzaro, R., Canzonieri, V., Florena, A. M., Biancone, L., Monteleone, G., Caronna, R., Ciardi, A., Elli, L., Caprioli, F., Vecchi, M., D'Inca, R., Zingone, F., D'Odorico, A., Lenti, M. V., Oreggia, B., Bonetti, L. R., Astegiano, M., Biletta, E., Cantoro, L., Giannone, A. G., Orlandi, A., Papi, C., Perfetti, V., Quaquarini, E., Sandri, G., Silano, M., Usai, P., Barresi, V., Ciccocioppo, R., Luinetti, O., Pedrazzoli, P., Pietrabissa, A., Viglio, A., Paulli, M., Corazza, G. R., Solcia, E., Vanoli, A., and Di Sabatino, A.

Published
2020

45. BTK inhibitors synergise with 5-FU to treat drug-resistant TP53-null colon cancers

Author

Lavitrano, M, Ianzano, L, Bonomo, S, Cialdella, A, Cerrito, M, Pisano, F, Missaglia, C, Giovannoni, R, Romano, G, Mclean, C, Voest, E, D'Amato, F, Noli, B, Ferri, G, Agostini, M, Pucciarelli, S, Helin, K, Leone, B, Canzonieri, V, Grassilli, E, Lavitrano, Marialuisa, Ianzano, Leonarda, Bonomo, Sara, Cialdella, Annamaria, Cerrito, Maria Grazia, Pisano, Fabio, Missaglia, Carola, Giovannoni, Roberto, Romano, Gabriele, McLean, Chelsea M, Voest, Emile E, D'Amato, Filomena, NOLI, BARBARA, Ferri, Gian Luca, Agostini, Marco, Pucciarelli, Salvatore, Helin, Kristian, Leone, Biagio Eugenio, Canzonieri, Vincenzo, Grassilli, Emanuela, Lavitrano, M, Ianzano, L, Bonomo, S, Cialdella, A, Cerrito, M, Pisano, F, Missaglia, C, Giovannoni, R, Romano, G, Mclean, C, Voest, E, D'Amato, F, Noli, B, Ferri, G, Agostini, M, Pucciarelli, S, Helin, K, Leone, B, Canzonieri, V, Grassilli, E, Lavitrano, Marialuisa, Ianzano, Leonarda, Bonomo, Sara, Cialdella, Annamaria, Cerrito, Maria Grazia, Pisano, Fabio, Missaglia, Carola, Giovannoni, Roberto, Romano, Gabriele, McLean, Chelsea M, Voest, Emile E, D'Amato, Filomena, NOLI, BARBARA, Ferri, Gian Luca, Agostini, Marco, Pucciarelli, Salvatore, Helin, Kristian, Leone, Biagio Eugenio, Canzonieri, Vincenzo, and Grassilli, Emanuela

Abstract

Colorectal cancer (CRC) is the fourth cause of death from cancer worldwide mainly due to the high incidence of drug-resistance. During a screen for new actionable targets in drug-resistant tumours we recently identified p65BTK – a novel oncogenic isoform of Bruton's tyrosine kinase. Studying three different cohorts of patients here we show that p65BTK expression correlates with histotype and cancer progression. Using drug-resistant TP53-null colon cancer cells as a model we demonstrated that p65BTK silencing or chemical inhibition overcame the 5-fluorouracil resistance of CRC cell lines and patient-derived organoids and significantly reduced the growth of xenografted tumours. Mechanistically, we show that blocking p65BTK in drug-resistant cells abolished a 5-FU-elicited TGFB1 protective response and triggered E2F-dependent apoptosis. Taken together, our data demonstrated that targeting p65BTK restores the apoptotic response to chemotherapy of drug-resistant CRCs and gives a proof-of-concept for suggesting the use of BTK inhibitors in combination with 5-FU as a novel therapeutic approach in CRC patients. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Published
2020

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