118 results on '"Pecciarini L"'
Search Results
2. 55P EGFR variant allele frequency (VAF) impacts on metastatic NSCLC patients outcome during first-line osimertinib
- Author
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Riva, S.T., Ogliari, F.R., Cangi, M.G., Bucci, G., Foggetti, G., Ferrara, R., Pecciarini, L., Oresti, S., Viganò, M.G., Damiano, G., Gandolfi, G., Guzzeloni, V., Valci, S., Ferrara, M., Nuccio, A., Venanzi, F.M., Pilotto, S., Bulotta, A., Milella, M., and Reni, M.
- Published
- 2023
- Full Text
- View/download PDF
3. Prospective Validation of the Italian Alliance Against Cancer Lung Panel in Patients With Advanced Non–Small-Cell Lung Cancer
- Author
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Gregorc, V., Mazzarella, L., Lazzari, C., Graziano, P., Vigneri, P., Genova, C., Toschi, L., Ciliberto, G., Bonanno, L., Delmonte, A., Bucci, G., Rossi, A., Motta, G., Coco, S., Marinello, A., Buglioni, S., Cangi, M. G., Di Micco, C., Bandiera, A., Bonfiglio, S., Pecciarini, L., Guida, A., Ceol, A., Frige', G., De Maria Marchiano, Ruggero, Pelicci, P. G., De Maria R. (ORCID:0000-0003-2255-0583), Gregorc, V., Mazzarella, L., Lazzari, C., Graziano, P., Vigneri, P., Genova, C., Toschi, L., Ciliberto, G., Bonanno, L., Delmonte, A., Bucci, G., Rossi, A., Motta, G., Coco, S., Marinello, A., Buglioni, S., Cangi, M. G., Di Micco, C., Bandiera, A., Bonfiglio, S., Pecciarini, L., Guida, A., Ceol, A., Frige', G., De Maria Marchiano, Ruggero, Pelicci, P. G., and De Maria R. (ORCID:0000-0003-2255-0583)
- Abstract
Background: The deeper knowledge of non–small-cell lung cancer (NSCLC) biology and the discovery of driver molecular alterations have opened the era of precision medicine in lung oncology, thus significantly revolutionizing the diagnostic and therapeutic approach to NSCLC. In Italy, however, molecular assessment remains heterogeneous across the country, and numbers of patients accessing personalized treatments remain relatively low. Nationwide programs have demonstrated that the creation of consortia represent a successful strategy to increase the number of patients with a molecular classification. Patients and Methods: The Alliance Against Cancer (ACC), a network of 25 Italian Research Institutes, has developed a targeted sequencing panel for the detection of genomic alterations in 182 genes in patients with a diagnosis of NSCLC (ACC lung panel). One thousand metastatic NSCLC patients will be enrolled onto a prospective trial designed to measure the sensitivity and specificity of the ACC lung panel as a tool for molecular screening compared to standard methods. Results and Conclusion: The ongoing trial is part of a nationwide strategy of ACC to develop infrastructures and improve competences to make the Italian research institutes independent for genomic profiling of cancer patients.
- Published
- 2021
4. Stress und Frühgeburt: Neuroendokriner Hintergrund von akutem und chronischem Stress als Auslöser für eine Frühgeburt
- Author
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Petraglia, F., Florio, P., Torricelli, M., Guidoni, C., Ignacchiti, E., Picciolini, E., Ciarmela, P., Fiore, G., Rossi, M., Severi, F. M., and Pecciarini, L.
- Published
- 2003
- Full Text
- View/download PDF
5. Chlamydia psittaci-eradicating antibiotic therapy in patients with advanced-stage ocular adnexal MALT lymphoma
- Author
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Ferreri, A. J. M., Dognini, G. P., Ponzoni, M., Pecciarini, L., Cangi, M. G., Santambrogio, G., Resti, A. G., De Conciliis, C., Magnino, S., Pasini, E., Vicari, N., Dolcetti, R., and Doglioni, C.
- Published
- 2008
6. Relationship between mode of delivery and neonatal calcium homeostasis
- Author
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Bagnoli, F., Bruchi, S., Garosi, G., Pecciarini, L., and Bracci, R.
- Published
- 1990
- Full Text
- View/download PDF
7. Modeling multiple myeloma-bone marrow interactions and response to drugs in a 3d surrogate microenvironment
- Author
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Belloni, D, Heltai, S, Ponzoni, M, Villa, A, Vergani, B, Pecciarini, L, Marcatti, M, Girlanda, S, Tonon, G, Ciceri, F, Caligaris-Cappio, F, Ferrarini, M, Ferrero, E, Belloni, Daniela, Heltai, Silvia, Ponzoni, Maurilio, Villa, Antonello, Vergani, Barbara, Pecciarini, Lorenza, Marcatti, Magda, Girlanda, Stefania, Tonon, Giovanni, Ciceri, Fabio, Caligaris-Cappio, Federico, Ferrarini, Marina, Ferrero, Elisabetta, Belloni, D, Heltai, S, Ponzoni, M, Villa, A, Vergani, B, Pecciarini, L, Marcatti, M, Girlanda, S, Tonon, G, Ciceri, F, Caligaris-Cappio, F, Ferrarini, M, Ferrero, E, Belloni, Daniela, Heltai, Silvia, Ponzoni, Maurilio, Villa, Antonello, Vergani, Barbara, Pecciarini, Lorenza, Marcatti, Magda, Girlanda, Stefania, Tonon, Giovanni, Ciceri, Fabio, Caligaris-Cappio, Federico, Ferrarini, Marina, and Ferrero, Elisabetta
- Abstract
Multiple myeloma develops primarily inside the bone marrow microenvironment, that confers pro-survival signals and drug resistance. 3D cultures that reproduce multiple myeloma-bone marrow interactions are needed to fully investigate multiple myeloma pathogenesis and response to drugs. To this purpose, we exploited the 3D Rotary Cell Culture System bioreactor technology for myelomabone marrow co-cultures in gelatin scaffolds. The model was validated with myeloma cell lines that, as assessed by histochemical and electronmicroscopic analyses, engaged contacts with stromal cells and endothelial cells. Consistently, pro-survival signaling and also cell adhesionmediated drug resistance were significantly higher in 3D than in 2D parallel co-cultures. The contribution of the VLA-4/VCAM1 pathway to resistance to bortezomib was modeled by the use of VCAM1 transfectants. Soluble factor-mediated drug resistance could be also demonstrated in both 2D and 3D co-cultures. The system was then successfully applied to co-cultures of primary myeloma cells-primary myeloma bone marrow stromal cells from patients and endothelial cells, allowing the development of functional myeloma-stroma interactions and MM cell long-term survival. Significantly, genomic analysis performed in a highrisk myeloma patient demonstrated that culture in bioreactor paralleled the expansion of the clone that ultimately dominated in vivo. Finally, the impact of bortezomib on myeloma cells and on specialized functions of the microenvironment could be evaluated. Our findings indicate that 3D dynamic culture of reconstructed human multiple myeloma microenvironments in bioreactor may represent a useful platform for drug testing and for studying tumor-stroma molecular interactions.
- Published
- 2018
8. Human malignant mesothelioma is recapitulated in immunocompetent BALB/c mice injected with murine AB cells
- Author
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Mezzapelle, R, Rrapaj, E, Gatti, E, Ceriotti, C, De Marchis, F, Preti, A, Spinelli, A, Perani, L, Venturini, M, Valtorta, S, Moresco, R, Pecciarini, L, Doglioni, C, Frenquelli, M, Crippa, L, Recordati, C, Scanziani, E, De Vries, H, Berns, A, Frapolli, R, Boldorini, R, D'Incalci, M, Bianchi, M, Crippa, M, Crippa, M., Valtorta, Silvia, MORESCO, ROSA MARIA, Mezzapelle, R, Rrapaj, E, Gatti, E, Ceriotti, C, De Marchis, F, Preti, A, Spinelli, A, Perani, L, Venturini, M, Valtorta, S, Moresco, R, Pecciarini, L, Doglioni, C, Frenquelli, M, Crippa, L, Recordati, C, Scanziani, E, De Vries, H, Berns, A, Frapolli, R, Boldorini, R, D'Incalci, M, Bianchi, M, Crippa, M, Crippa, M., Valtorta, Silvia, and MORESCO, ROSA MARIA
- Abstract
Malignant Mesothelioma is a highly aggressive cancer, which is difficult to diagnose and treat. Here we describe the molecular, cellular and morphological characterization of a syngeneic system consisting of murine AB1, AB12 and AB22 mesothelioma cells injected in immunocompetent BALB/c mice, which allows the study of the interplay of tumor cells with the immune system. Murine mesothelioma cells, like human ones, respond to exogenous High Mobility Group Box 1 protein, a Damage-Associated Molecular Pattern that acts as a chemoattractant for leukocytes and as a proinflammatory mediator. The tumors derived from AB cells are morphologically and histologically similar to human MM tumors, and respond to treatments used for MM patients. Our system largely recapitulates human mesothelioma, and we advocate its use for the study of MM development and treatment.
- Published
- 2016
9. Bcl2, Bcl6, MYC, MALT 1 and Bcl10 rearrangements in nodal diffuse large B-cell lymphomas: A multicenter evaluation of a new set of fish probes and correlation with clinical outcome
- Author
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Tibiletti, M., Martin, V., Bernasconi, B., Del Curto, B., Pecciarini, L., Uccella, S., Giancarlo Pruneri, Ponzoni, M., Mazzucchelli, L., Martinelli, G., Pinotti, G., Ferreri, A., Doglioni, C., Zucca, E., Capella, C., Bertoni, F., Tibiletti, M, Martin, V, Bernasconi, B, Del Curto, B, Pecciarini, L, Uccella, S, Pruneri, G, Ponzoni, Maurilio, Mazzucchelli, L, Martinelli, G, Pinotti, G, Ferreri, A, Doglioni, Claudio, Zucca, E, Capella, C, and Bertoni, F.
- Published
- 2008
10. Immunoglobulin Gene Repertoire in Ocular Adnexa Lymphomas (OAL): Hints on the Nature of the Antigenic Stimulation
- Author
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Dagklis A, Ponzoni M, Ferreri AJM, Giulia M, Pecciarini L, Dolcetti R, Stamatopoulos K, Doglioni C, Ghia P, Dagklis, A, Ponzoni, M, Ferreri, Ajm, Giulia, M, Pecciarini, L, Dolcetti, R, Stamatopoulos, K, Doglioni, C, and Ghia, P
- Published
- 2008
11. CHLAMYDOPHILA PSITTACI (CP) IS VIABLE AND INFECTIOUS IN THE CONJUNCTIVA AND PERIPHERAL BLOOD OF PATIENTS WITH OCULAR ADNEXAL MALT LYMPHOMA (OAML): RESULTS OF A PROSPECTIVE CASE-CONTROL STUDY
- Author
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Ferreri, J. M., Riccardo Dolcetti, Dognini, P., Malabarba, L., Vicari, N., Pasini, E., Ponzoni, M., Cangi, M. G., Pecciarini, L., Resti, A. Giordano, Rossini, S., Doglioni, C., Magnino, S., Ferreri, Jm, Dolcetti, R, Dognini, P, Malabarba, L, Vicari, N, Pasini, E, Ponzoni, Maurilio, Cangi, Mg, Pecciarini, L, Resti, Ag, Rossini, S, Doglioni, C, and Magnino, S.
- Published
- 2008
12. Prevalence of Chlamydia psittaci infection in nodal and extranodal non-Hodgkin lymphomas
- Author
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Ferreri, J. M., Dolcetti, R., Guidoboni, M., Maria Giulia Cangi, Pecciarini, L., Dognini, G. P., Ghia, P. P., Malnati, M., Pasini, E., Doglioni, C., Ponzoni, M., Ferreri, Jm, Dolcetti, R, Guidoboni, M, Cangi, Mg, Pecciarini, L, Dognini, Gp, Ghia, Pp, Malnati, M, Pasini, E, Doglioni, C, and Ponzoni, M
- Published
- 2007
13. HER-2/neu borderline nel carcinoma della mammella: una nuova categoria in FISH
- Author
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Balzarini, Piera, LO CONSULO, C., Cangi, M. G., Benerini, L., Grigolato, Pier Giovanni, Iuzzolino, P., Doglioni, C., and Pecciarini, L.
- Published
- 2008
14. Characterization of t(6,11)(p21;q12) in renal cell carcinoma of an adult patient
- Author
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Pecciarini, L, Cangi, M, LO CUNSOLO, C, Macri', E, DAL CIN, E, Martignoni, Guido, and Doglioni, C.
- Published
- 2007
15. Carcinomi con traslocazioni coinvolgenti i geni della famiglia MiTF/TFE
- Author
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Gobbo, S, Tardanico, R, Martignoni, Guido, Pea, Maurizio, Pecciarini, L, Brunelli, Matteo, Balzarini, P, Macri, E, Cossu Rocca, P, Chilosi, Marco, Menestrina, Fabio, and Doglioni, C.
- Published
- 2005
16. Neuroendocrinology of human placenta
- Author
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Petraglia, F., Florio, P., Luisi, S., Severi, F. M., Bocchi, C., Torricelli, M., Cobellis, L., Centini, G., Guidoni, G., Pecciarini, L., Cito, G., and Picciolini, E.
- Published
- 2003
17. Inhibins and activins in pregnancy
- Author
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Petraglia, F., Florio, P., Luisi, S., Severi, F. M., Ciarmela, P., Picciolini, E., Pecciarini, L., Cobellis, L., Bocchi, C., Bagnoli, F., and Buonocore, G.
- Published
- 2003
18. p53-p63 cross-talk in lymphomas
- Author
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Doglioni, C, Cangi, G, Pecciarini, L, Zamo', Alberto, Canal, F, and Chilosi, Marco
- Published
- 2002
19. Absent C-reactive response in early-onset neonatal sepsi. Relation to clinical characteristics and outcome
- Author
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De Felice, C., Liberatori, S., Bini, Luca, Stabile, M. E., Magi, Barbara, Marzocchi, Barbara, Pecciarini, L., Pallini, V., and Bracci, R.
- Published
- 1997
20. Estroprogestinici e mammella: indicazioni e controindicazioni nelle adolescenti
- Author
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Franchi, F, Vanni, A, Funicelli, V, Cresti, M, Giovani, M, Pecciarini, L, and Gioffre', WALTER RENATO
- Published
- 1992
21. A Woman and Her Canary: A Tale of Chlamydiae and Lymphomas
- Author
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Ferreri, A. J. M., primary, Dolcetti, R., additional, Magnino, S., additional, Doglioni, C., additional, Cangi, M. G., additional, Pecciarini, L., additional, Ghia, P., additional, Dagklis, A., additional, Pasini, E., additional, Vicari, N., additional, Dognini, G. P., additional, Resti, A. G., additional, and Ponzoni, M., additional
- Published
- 2007
- Full Text
- View/download PDF
22. Stress und Frühgeburt
- Author
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Petraglia, F., primary, Florio, P., additional, Torricelli, M., additional, Guidoni, C., additional, Ignacchiti, E., additional, Picciolini, E., additional, Ciarmela, P., additional, Fiore, G., additional, Rossi, M., additional, Severi, F. M., additional, and Pecciarini, L., additional
- Published
- 2003
- Full Text
- View/download PDF
23. Identifying the primary sites of metastatic carcinoma: the increasing role of immunohistochemistry
- Author
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Pecciarini, L., primary, Giulia Cangi, M., additional, and Doglioni, C., additional
- Published
- 2001
- Full Text
- View/download PDF
24. Syndecan-1 (CD138) expression in human breast carcinoma is associated with an aggressive phenotype and appears related to a poor prognosis and low response to adjuvant chemotherapy
- Author
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Galligioni, E., primary, Barbareschi, M., additional, Aldovini, D., additional, Maisonneuuve, P., additional, Cangi, M.G., additional, Pecciarini, L., additional, Caffo, O., additional, Arcuri, C., additional, Dalla Palma, P., additional, and Doglioni, C., additional
- Published
- 2001
- Full Text
- View/download PDF
25. Interphase cytogenetics of gastric adenocarcinomas
- Author
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Gargano, D., primary, Galli, M., additional, Matucci, M., additional, Palli, D., additional, Parenti, A., additional, Pecciarini, L., additional, Rubeca, T., additional, and Turco, P., additional
- Published
- 1996
- Full Text
- View/download PDF
26. SAFETY AND EFFICACY OF THE “CARMEN” REGIMEN, A NEW DOSE‐DENSE SHORT‐TERM THERAPY IN PATIENTS WITH AGGRESSIVE B‐CELL LYMPHOMA AND MYC REARRANGEMENT.
- Author
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Ferreri, A. J. M, Angelillo, P, Erbella, F, Liberatore, C, Cattaneo, C, Verga, L, Lleshi, A, Allione, B, Facchetti, F, Ponzoni, M, Pagani, C, Foppoli, M, Pecciarini, L, Sassone, M. C, Flospergher, E, Rossi, G, Spina, M, and A. Re
- Published
- 2021
- Full Text
- View/download PDF
27. A screening study of Chlamydia psittaci infection in 172 cases of nodal and extranodal non-hodgkin lymphomas
- Author
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Ferren, A. J. M., Dolcetti, R., Guidoboni, M., Maria Giulia Cangi, Pecciarini, L., Dognini, G. P., Ghia, P., Malnati, M., Pasini, E., Doglioni, C., Ponzoni, M., Ferren, Ajm, Dolcetti, R, Guidoboni, M, Cangi, Mg, Pecciarini, L, Dognini, Gp, Ghia, P, Malnati, M, Pasini, E, Doglioni, C, and Ponzoni, M
28. Malformazioni fetali riscontrate con ultrasuoni in un solo gemello in corso di gravidanze plurime. Considerazioni medico legali su 4 casi [Fetal malformations detected by ultrasonics in a twin in multiple pregnancies. Medico-legal considerations on 4 cases]
- Author
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Norelli, G. A., Centini, G., Calvelli, P., Pecciarini, L., Monti, E., and Severi, F. M.
- Published
- 1988
29. Range di normalità dell'alpha-fetoproteina nel liquido amniotico e nel plasma materno [Normal range of alpha-fetoprotein in amniotic fluid and maternal plasma]
- Author
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Monti, E., gabriele centini, Landi, D., Pecciarini, L., Pasqui, L., and Severi, Filiberto Maria
- Published
- 1987
30. High incidence of histologic chorioamnionitis in women with gestational vaginal bleeding [1]
- Author
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Claudio De Felice, Toti, P., Picciolini, E., Massafra, C., Pecciarini, L., Palmeri, M. L. D., and Bracci, R.
31. p63, a p53 analogue, is a selective myoepithelial nuclear marker in human breast tissue and neoplasms
- Author
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Barbareschi, M., Pecciarini, L., Maria Giulia Cangi, Macri, E., Rizzo, A., Viale, G., and Doglioni, C.
32. Teriparatide acetate (hsPTH 1-34): A candidate drug for the prevention of preterm labor? [1]
- Author
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Bagnoli, F., Molina, E., Felice, C., Castelli, M. C., Pecciarini, L., and Vincenzo De Leo
33. Stress and preterm birth. Neuro-endocrine background of acute and chronic stress initiating preterm delivery | Stress und frühgeburt: Neuroendokriner hintergrund von akutem und chronischem stress als auslöser für eine frühgeburt
- Author
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Petraglia, F., Florio, P., Torricelli, M., Guidoni, C., Ignacchiti, E., Picciolini, E., Ciarmela, P., Fiore, G., Rossi, M., Filiberto Maria SEVERI, and Pecciarini, L.
34. The role of immunohistochemistry in the differential diagnosis of serous effusions
- Author
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Maria Giulia Cangi, Pecciarini, L., and Doglioni, C.
35. Alterations of β-Catenin Pathway in Non-Melanoma Skin Tumors: Loss of α-ABC Nuclear Reactivity Correlates with the Presence of β-Catenin Gene Mutation
- Author
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Doglioni, C., Piccinin, S., Demontis, S., Cangi, M. G., Pecciarini, L., Chiarelli, C., Armellin, M., Vukosavljevic, T., Boiocchi, M., and Roberta Maestro
36. Small thymus in very low birth weight infants born to mothers with subclinical chorioamnionitis
- Author
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De Felice, C., Toti, P., Santopietro, R., Stumpo, M., Pecciarini, L., and Bagnoli, F.
- Abstract
Chorioamnionitis, a major cause of preterm birth with significant neonatal morbidity and mortality, frequently occurs in mothers who are free of symptoms. A combined clinical, radiologic, and pathologic study of 129 very low birth weight infants indicated a significant association between a markedly decreased thymic size at birth and subclinical chorioamnionitis. (J Pediatr 1999;135:384-6)
- Published
- 1999
- Full Text
- View/download PDF
37. Establishment and Characterization of PCL12, a Novel CD5+ Chronic Lymphocytic Leukaemia Cell Line
- Author
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Pamela Ranghetti, Maria Teresa Sabrina Bertilaccio, Gabriella Leone, Benedetta Apollonio, Federica Barbaglio, Cristina Scielzo, Maurilio Ponzoni, Lydia Scarfò, Andreas Agathangelidis, Paolo Ghia, Lorenza Pecciarini, Valeria De Pascali, Federico Caligaris-Cappio, Agathangelidis, A, Scarfò, L, Barbaglio, F, Apollonio, B, Bertilaccio, Mt, Ranghetti, P, Ponzoni, M, Leone, G, De Pascali, V, Pecciarini, L, Ghia, PAOLO PROSPERO, Caligaris Cappio, F, Scielzo, C., Agathangelidis, A., Scarfo', L., Barbaglio, F., Apollonio, B., Bertilaccio, M. T., Ranghetti, P., Ponzoni, M., Leone, G., De Pascali, V., Pecciarini, L., Ghia, P., and Caligaris-Cappio, F.
- Subjects
Chronic lymphocytic leukemia ,lcsh:Medicine ,Biology ,CD5 Antigens ,CD19 ,Mice ,immune system diseases ,Cell Line, Tumor ,hemic and lymphatic diseases ,Calcium flux ,medicine ,Animals ,Humans ,lcsh:Science ,Gene Rearrangement ,CD20 ,ZAP-70 Protein-Tyrosine Kinase ,Multidisciplinary ,ZAP70 ,lcsh:R ,hemic and immune systems ,Gene rearrangement ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Phenotype ,biology.protein ,Cancer research ,lcsh:Q ,CD5 ,Immortalised cell line ,Neoplasm Transplantation ,Research Article - Abstract
Immortalized cell lines representative of chronic lymphocytic leukemia (CLL) can assist in understanding disease pathogenesis and testing new therapeutic agents. At present, very few representative cell lines are available. We here describe the characterization of a new cell line (PCL12) that grew spontaneously from the peripheral blood (PB) of a CLL patient with progressive disease and EBV infection. The CLL cell origin of PCL12 was confirmed after the alignment of its IGH sequence against the “original” clonotypic sequence. The IGH gene rearrangement was truly unmutated and no CLL-related cytogenetic or genetic lesions were detected. PCL12 cells express CD19, CD20, CD5, CD23, low levels of IgM and IgD and the poor-outcome-associated prognostic markers CD38, ZAP70 and TCL1. In accordance with its aggressive phenotype the cell line is inactive in terms of LYN and HS1 phosphorylation. BcR signalling pathway is constitutively active and anergic in terms of p-ERK and Calcium flux response to α-IgM stimulation. PCL12 cells strongly migrate in vitro in response to SDF-1 and form clusters. Finally, they grow rapidly and localize in all lymphoid organs when xenotrasplanted in Rag2-/-γc-/- mice. PCL12 represents a suitable preclinical model for testing pharmacological agents.
- Published
- 2015
38. Intratumoral cellular heterogeneity: Implications for drug resistance in patients with non-small cell lung cancer
- Author
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Maria Grazia Viganò, Vanesa Gregorc, Francesca Rita Ogliari, Greta Grassini, Lorenza Pecciarini, Aurora Mirabile, Gianluigi Arrigoni, Alessandra Bulotta, Maria Giulia Cangi, Claudio Doglioni, Chiara Lazzari, Abdelrahman Khater, Stefania Ippati, Mario Mandalà, Giulia Veronesi, Gregorc, V., Lazzari, C., Mandala, M., Ippati, S., Bulotta, A., Cangi, M. G., Khater, A., Vigano, M. G., Mirabile, A., Pecciarini, L., Ogliari, F. R., Arrigoni, G., Grassini, G., Veronesi, G., and Doglioni, C.
- Subjects
0301 basic medicine ,Oncology ,Genome instability ,Genomic instability ,Cancer Research ,medicine.medical_specialty ,Tumor heterogeneity ,Review ,Drug resistance ,NSCLC ,03 medical and health sciences ,0302 clinical medicine ,Non-small cell lung cancer ,Internal medicine ,medicine ,In patient ,Epigenetics ,Lung cancer ,RC254-282 ,Targeted agents ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer cell ,Non small cell ,business - Abstract
Simple Summary The number of druggable tumor-specific molecular alterations in the treatment of non-small cell lung cancer (NSCLC) has grown significantly in the past decade. Emerging technologies such as liquid biopsy and single-cell methods allow for studying targetable drivers and develop personalized treatments. However, although new therapies confer prolonged disease control and high tumor response rates, most patients eventually progress on targeted treatments. Intratumoral heterogeneity is a frequent event in NSCLC, driving the tumor cells to develop adaptive or new resistance mechanisms within the drug environment. This review summarizes the current and upcoming research on the biological role of tumor heterogeneity, highlighting the link between early and acquired drug resistance and tumoral heterogeneity in targetable driver mutated NSCLC. Abstract Tailored therapies based on the identification of molecular targets currently represent a well-established therapeutic scenario in the treatment of non-small cell lung cancer (NSCLC) patients. However, while aiming to improve patients’ response to therapy, development of resistance is frequently observed in daily clinical practice. Intratumoral heterogeneity is a frequent event in NSCLC, responsible for several critical issues in patients’ diagnosis and treatment. Advances in single-cell sequencing technologies have allowed in-depth profiling of tumors and attributed intratumoral heterogeneity to genetic, epigenetic, and protein modification driven diversities within cancer cell populations. This review highlights current research on the biological role of tumor heterogeneity and its impact on the development of acquired resistance in NSCLC patients.
- Published
- 2021
39. Evidence of a common cell origin in a case of pancreatic mixed intraductal papillary mucinous neoplasm–neuroendocrine tumor
- Author
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Lorenza Pecciarini, Greta Grassini, Claudio Doglioni, Renaud Maire, Marco Schiavo Lena, Aurel Perren, Maria Giulia Cangi, Ilaria Francaviglia, Massimo Falconi, Stefano Partelli, Schiavo Lena, M., Cangi, M. G., Pecciarini, L., Francaviglia, I., Grassini, G., Maire, R., Partelli, S., Falconi, M., Perren, A., and Doglioni, C.
- Subjects
0301 basic medicine ,Male ,Pathology ,medicine.medical_specialty ,KRAS and GNAS mutation ,Adenoma ,Cell ,DNA Mutational Analysis ,Pancreatic Intraductal Neoplasms ,medicine.disease_cause ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,CDKN2A ,Pancreatic neuroendocrine tumor ,medicine ,GNAS complex locus ,Biomarkers, Tumor ,Humans ,Cyclin D1 amplification ,610 Medicine & health ,Molecular Biology ,biology ,Intraductal papillary mucinous neoplasm ,Precursor lesion ,Mixed neuroendocrine non-neuroendocrine neoplasms ,Cell Biology ,General Medicine ,Middle Aged ,medicine.disease ,Adenocarcinoma, Mucinous ,CDKN2A mutation ,Carcinoma, Papillary ,Pancreatic Neoplasms ,stomatognathic diseases ,Neuroendocrine Tumors ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,biology.protein ,570 Life sciences ,KRAS ,Who classification ,Carcinoma, Pancreatic Ductal - Abstract
Recently, the term mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) has been proposed as an umbrella definition covering different possible combinations of mixed neuroendocrine-exocrine neoplasms. Among these, the adenoma plus neuroendocrine tumor (NET) combination is among the rarest and not formally recognized by the 2019 WHO Classification. In this setting, the debate between either collision tumors or true mixed neoplasms is still unsolved. In this report, a pancreatic intraductal papillary mucinous neoplasm (IPMN) plus a NET is described, and the molecular investigations showed the presence in both populations of the same KRAS, GNAS, and CDKN2A mutations and the amplification of the CCND1 gene. These data prove clonality and support a common origin of both components, therefore confirming the true mixed nature. For this reason, mixed neuroendocrine-exocrine neoplasms, in which the exocrine component is represented by a glandular precursor lesion (adenoma/IPMN) only, should be included into the MiNEN family.
- Published
- 2020
40. Identification and monitoring of somatic mutations in circulating cell-free tumor DNA in lung cancer patients
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Emanuela Brunetto, Greta Grassini, Chiara Lazzari, Lorenza Pecciarini, Ilaria Francaviglia, Vanesa Gregorc, Daniela Medicina, Alessandra Bulotta, Elena Dal Cin, Maria Giulia Cangi, Salvatore Girlando, Claudio Doglioni, Chanel Smart, Gilda Magliacane, Francaviglia, I., Magliacane, G., Lazzari, C., Grassini, G., Brunetto, E., Dal Cin, E., Girlando, S., Medicina, D., Smart, C. E., Bulotta, A., Gregorc, V., Pecciarini, L., Doglioni, C., and Cangi, M. G.
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Drug resistance ,Target therapy ,Molecular diagnostic ,Circulating Tumor DNA ,03 medical and health sciences ,T790M ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Internal medicine ,Positron Emission Tomography Computed Tomography ,Biopsy ,medicine ,Biomarkers, Tumor ,Humans ,Molecular Targeted Therapy ,Lung cancer ,Lung ,Protein Kinase Inhibitors ,In Situ Hybridization, Fluorescence ,Aged ,Aged, 80 and over ,Massive parallel sequencing ,medicine.diagnostic_test ,business.industry ,Liquid Biopsy ,High-Throughput Nucleotide Sequencing ,ctDNA ,DNA, Neoplasm ,Middle Aged ,medicine.disease ,Molecular diagnostics ,Resistance mutation ,030104 developmental biology ,NGS ,030220 oncology & carcinogenesis ,Mutation ,Female ,EGFR Activating Mutation ,business - Abstract
Objectives Circulating cell-free tumor DNA (ctDNA) isolated from the peripheral blood of non-small-cell lung cancer (NSCLC) patients provides biomarkers for both therapeutic target selection, particularly when direct tumor biopsy is unfeasible, and also for drug resistance monitoring. This study evaluates the reliability and feasibility of ctDNA analysis in an in-house clinical molecular diagnostic workflow. Materials and methods Mutation profiling by both standard methods and Next-Generation sequencing (NGS) was carried out and compared on 2 independent lung cancer patient cohorts. Cohort 1 consisted of 50 EGFR-mutated NSCLC patients, established on tumour biopsy, for whom ctDNA was collected at disease progression after TKI-inhibitor treatment and could be used to monitor drug resistance. Cohort 2 consisted of 50 newly diagnosed lung cancer patients for whom tumour biopsy was not possible and only ctDNA was available, providing the possibility of biomarker identification. Results ctDNA analysis of Cohort 1 verified the persistence of the tumour-detected EGFR activating mutation at disease progression by both standard and NGS methods, in 84% and 92% of the cases respectively. The T790M EGFR resistance mutation was identified in 71% of the ctDNA EGFR mutated samples providing vital information for their disease management. In newly diagnosed Cohort 2 patients, EGFR activating mutations were detected in 16% of the patients by both standard and NGS analysis of ctDNA in peripheral blood, providing indication to targeted-therapy otherwise unavailable for this group of patients. Conclusion The presented study investigated lung cancer ctDNA analysis, comparing conventional methods versus NGS sequencing, and demonstrated the successful use of plasma ctDNA as a template for targeted NGS tumor gene panel in an in-house routine clinical practice. More importantly, these data underline the advantages of the clinical application of ctDNA NGS analysis for identification of therapeutic targets, real-time monitoring of therapy, and resistance mechanisms in lung cancer patients.
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- 2019
41. MYD88 L265P MUTATION DETECTION IN THE AQUEOUS HUMOR OF PATIENTS WITH VITREORETINAL LYMPHOMA
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Chiara Giuffrè, Elisabetta Miserocchi, Francesco Bandello, Maurilio Ponzoni, Teresa Calimeri, Giulio Modorati, Lorenza Pecciarini, Andrés J.M. Ferreri, Ilaria Francaviglia, Maria Giulia Cangi, Miserocchi, E., Ferreri, A. J. M., Giuffre, C., Cangi, M. G., Francaviglia, I., Calimeri, T., Ponzoni, M., Pecciarini, L., Bandello, F. M., and Modorati, G. M.
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Male ,genetic structures ,medicine.medical_treatment ,DNA Mutational Analysis ,Vitrectomy ,Polymerase Chain Reaction ,anterior chamber paracentesis ,law.invention ,0302 clinical medicine ,Intraocular Lymphoma ,law ,Paracentesis ,Medicine ,Prospective Studies ,Prospective cohort study ,Polymerase chain reaction ,Aged, 80 and over ,medicine.diagnostic_test ,Primary central nervous system lymphoma ,vitreoretinal lymphoma ,General Medicine ,DNA, Neoplasm ,Middle Aged ,MYD88 L265P mutation ,030220 oncology & carcinogenesis ,Mutation (genetic algorithm) ,Female ,Waldenstrom Macroglobulinemia ,medicine.medical_specialty ,Aqueous humor ,Slit Lamp Microscopy ,Aqueous Humor ,03 medical and health sciences ,Ophthalmology ,Biomarkers, Tumor ,Humans ,Aged ,primary central nervous system lymphoma ,business.industry ,medicine.disease ,eye diseases ,Vitreous Body ,Mutation ,Myeloid Differentiation Factor 88 ,030221 ophthalmology & optometry ,sense organs ,business ,Vitreoretinal lymphoma - Abstract
Purpose To detect the presence of MYD88 L265P mutation in the aqueous humor of patients with cytologically proven vitreoretinal lymphoma. Methods Eight consecutive patients with bilateral vitreoretinal lymphoma (16 eyes) were prospectively evaluated. Genomic DNA was extracted from aqueous samples after paracentesis and vitreous humor samples after diagnostic vitrectomy. MYD88 codon 265 mutation was investigated by both amplification-refractory mutation system polymerase chain reaction approach and pyrosequencing assay in the aqueous humor of all patients and in the vitreous of 6 patients. A control group of 8 age-matched patients with established diagnosis of noninfectious uveitis was also tested for the presence of MYD88 L265P mutation in the aqueous humor. Results Eight patients (three men, five women) with mean age of 69.5 years (range 50-85 years) were considered. All the patients tested for MYD88 L265P in the vitreous (six) were positive, and this result was consistent with cytological examination in all samples but one. The MYD88 L265P mutation was found in the aqueous of 6 patients (75%), and in 3 of them, the mutation was present in both eyes. Results of MYD88 L265P mutation in aqueous and vitreous sample were consistent in 7 of the 8 eyes with available samples. The aqueous humor of the noninfectious uveitis control group was negative for the detection of MYD88 L265P mutation. Conclusion MYD88 mutation was detected in the aqueous humor of 75% of patients with cytologically proven vitreoretinal lymphoma. This technique may be considered as an additional diagnostic tool in the detection of the disease.
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- 2018
42. Modeling multiple myeloma-bone marrow interactions and response to drugs in a 3d surrogate microenvironment
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Stefania Girlanda, Marina Ferrarini, Lorenza Pecciarini, Elisabetta Ferrero, Federico Caligaris-Cappio, Magda Marcatti, Giovanni Tonon, Maurilio Ponzoni, Antonello Villa, Silvia Heltai, Barbara Vergani, Fabio Ciceri, Daniela Belloni, Belloni, D, Heltai, S, Ponzoni, M, Villa, A, Vergani, B, Pecciarini, L, Marcatti, M, Girlanda, S, Tonon, G, Ciceri, F, Caligaris-Cappio, F, Ferrarini, M, Ferrero, E, Belloni, Daniela, Heltai, Silvia, Ponzoni, Maurilio, Villa, Antonello, Vergani, Barbara, Pecciarini, Lorenza, Marcatti, Magda, Girlanda, Stefania, Tonon, Giovanni, Ciceri, Fabio, Caligaris-Cappio, Federico, Ferrarini, Marina, and Ferrero, Elisabetta
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0301 basic medicine ,3D model ,medicine.medical_specialty ,Stromal cell ,Cell Survival ,Cell Culture Techniques ,Drug Resistance ,Cell Communication ,Models, Biological ,Article ,Plasma Cell Disorders ,Bortezomib ,03 medical and health sciences ,Bioreactors ,0302 clinical medicine ,Bone Marrow ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Cell Adhesion ,Tumor Microenvironment ,medicine ,Humans ,Multiple myeloma ,Tumor microenvironment ,Hematology ,Chemistry ,Endothelial Cells ,medicine.disease ,Coculture Techniques ,Bone Marrow Microenvironment ,030104 developmental biology ,medicine.anatomical_structure ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,Gelatin ,Bone marrow ,Stromal Cells ,Clone (B-cell biology) ,Multiple Myeloma ,medicine.drug - Abstract
Multiple myeloma develops primarily inside the bone marrow microenvironment, that confers pro-survival signals and drug resistance. 3D cultures that reproduce multiple myeloma-bone marrow interactions are needed to fully investigate multiple myeloma pathogenesis and response to drugs. To this purpose, we exploited the 3D Rotary Cell Culture System bioreactor technology for myeloma-bone marrow co-cultures in gelatin scaffolds. The model was validated with myeloma cell lines that, as assessed by histochemical and electron-microscopic analyses, engaged contacts with stromal cells and endothelial cells. Consistently, pro-survival signaling and also cell adhesion-mediated drug resistance were significantly higher in 3D than in 2D parallel co-cultures. The contribution of the VLA-4/VCAM1 pathway to resistance to bortezomib was modeled by the use of VCAM1 transfectants. Soluble factor-mediated drug resistance could be also demonstrated in both 2D and 3D co-cultures. The system was then successfully applied to co-cultures of primary myeloma cells-primary myeloma bone marrow stromal cells from patients and endothelial cells, allowing the development of functional myeloma-stroma interactions and MM cell long-term survival. Significantly, genomic analysis performed in a high-risk myeloma patient demonstrated that culture in bioreactor paralleled the expansion of the clone that ultimately dominated in vivo. Finally, the impact of bortezomib on myeloma cells and on specialized functions of the microenvironment could be evaluated. Our findings indicate that 3D dynamic culture of reconstructed human multiple myeloma microenvironments in bioreactor may represent a useful platform for drug testing and for studying tumor-stroma molecular interactions.
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- 2018
43. Establishment, characterization and long-term culture of human endocrine pancreas-derived microvascular endothelial cells
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Augusto Pessina, Emilio Ciusani, Lorenza Pecciarini, Giulio Alessandri, Anna Ferri, Rita Nano, Silvia Pellegrini, Lorenzo Piemonti, Erica Dugnani, Luisa Pascucci, Valeria Sordi, Valentina Ceserani, Sordi, V., Ferri, A., Ceserani, V., Ciusani, E., Dugnani, E., Pellegrini, S., Nano, R., Pecciarini, L., Pessina, A., Pascucci, L., Piemonti, Lorenzo, Alessandri, G., and Pathology/molecular and cellular medicine
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0301 basic medicine ,CD31 ,Vascular Endothelial Growth Factor A ,Cancer Research ,medicine.medical_specialty ,Endothelium ,Angiogenesis ,endothelial cell line ,islets ,pancreas ,primary culture ,Immunology ,Biology ,03 medical and health sciences ,chemistry.chemical_compound ,Islets of Langerhans ,Antigens, CD ,Internal medicine ,von Willebrand Factor ,Journal Article ,medicine ,Immunology and Allergy ,Humans ,Genetics (clinical) ,Cells, Cultured ,Transplantation ,Vascular Endothelial Growth Factor Receptor-1 ,Research Support, Non-U.S. Gov't ,Pancreatic islets ,Interleukin-8 ,Endothelial Cells ,Cell Biology ,Cadherins ,Cell biology ,Vascular endothelial growth factor ,Endothelial stem cell ,Vascular endothelial growth factor A ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Oncology ,Vascular endothelial growth factor C ,chemistry ,Microvessels ,Endothelium, Vascular - Abstract
Background In vitro primary cultures of microvascular endothelial cells from endocrine pancreas are difficult to obtain, but can be a very helpful tool for studies of islet biology, transplantation and regenerative medicine. Methods We applied a protocol recently described for the isolation and culture of brain microvascular endothelial cells (EC) on human pancreatic islets. EC obtained were characterized in terms of morphological (light and transmission electron microscopy), phenotypical (by immunofluorescence and flow cytometry) and functional (cord formation assay and protein secretion by multiplex bead-based assay) characteristics. Results EC were obtained from 25% of islet preparations processed. Two primary endothelial cell lines showed high proliferative potential and were deeply characterized: they presented endothelial cell morphology and expressed CD31, CD49a, CD49e, CD34, von Willebrand Factor (vWF), Vascular Endothelial CAdherin (VE-CAD), Tyrosine Kinase with Ig and EGF Homology Domains-2 (TIE2), Vascular Endothelial Growth Factor Receptor 1 (VEGFR1), Ulex lectin and the endothelium endocrine-specific marker nephrin. Besides, they were able to form cordons in vitro and secreted factors involved in the process of angiogenesis such as Vascular Endothelial Growth Factor (VEGF), Monocyte Chemotactic Protein 1 (MCP-1), interleukin (IL)-8 and Melanoma Growth Stimulatory Activity Alpha (GROα). These cell lines were termed Human Islet Microvascular Endothelial Cells (HIMEC). Discussion This study establishes a simple and effective strategy for isolation and long-term culture of EC derived from human pancreatic islet. HIMEC in culture preserve phenotype and functional properties and are, therefore, a useful tool for future experiments of in vitro pancreas modelling, co-transplantation with pancreatic islets, re-vascularization of scaffold or matrix for regenerative medicine purposes. © 2017 International Society for Cellular Therapy
- Published
- 2016
44. Human malignant mesothelioma is recapitulated in immunocompetent BALB/c mice injected with murine AB cells
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Hilda de Vries, Roberta Frapolli, Elena Gatti, Camilla Recordati, Michela Frenquelli, Maurizio D'Incalci, Marco Bianchi, Massimo Venturini, Antonello E. Spinelli, Francesco De Marchis, Luca Crippa, Renzo Boldorini, Eltjona Rrapaj, Rosanna Mezzapelle, Eugenio Scanziani, Claudio Doglioni, Massimo P. Crippa, Chiara Ceriotti, Laura Perani, Silvia Valtorta, Lorenza Pecciarini, Alessandro Preti, Rosa Maria Moresco, Anton Berns, Mezzapelle, R, Rrapaj, E, Gatti, E, Ceriotti, C, De Marchis, F, Preti, A, Spinelli, A, Perani, L, Venturini, M, Valtorta, S, Moresco, R, Pecciarini, L, Doglioni, C, Frenquelli, M, Crippa, L, Recordati, C, Scanziani, E, De Vries, H, Berns, A, Frapolli, R, Boldorini, R, D'Incalci, M, Bianchi, M, Crippa, M, Spinelli, Ae, Moresco, Rm, Doglioni, Claudio, de Vries, H, D’Incalci, M, Bianchi, MARCO EMILIO, and Crippa, Mp
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Mesothelioma ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Antineoplastic Agents ,Pemetrexed ,HMGB1 ,Deoxycytidine ,Article ,Proinflammatory cytokine ,BALB/c ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Malignant Mesotheliom ,Cell Line, Tumor ,medicine ,Mesothelioma, HMGB1, in vivo, imaging ,cancer ,Animals ,Humans ,HMGB1 Protein ,Cisplatin ,Mice, Inbred BALB C ,Multidisciplinary ,biology ,business.industry ,Mesothelioma, Malignant ,biology.organism_classification ,medicine.disease ,Survival Analysis ,Gemcitabine ,030104 developmental biology ,Cell culture ,mesothelioma ,030220 oncology & carcinogenesis ,biology.protein ,Female ,business ,Immunocompetence ,Neoplasm Transplantation ,medicine.drug - Abstract
Malignant Mesothelioma is a highly aggressive cancer, which is difficult to diagnose and treat. Here we describe the molecular, cellular and morphological characterization of a syngeneic system consisting of murine AB1, AB12 and AB22 mesothelioma cells injected in immunocompetent BALB/c mice, which allows the study of the interplay of tumor cells with the immune system. Murine mesothelioma cells, like human ones, respond to exogenous High Mobility Group Box 1 protein, a Damage-Associated Molecular Pattern that acts as a chemoattractant for leukocytes and as a proinflammatory mediator. The tumors derived from AB cells are morphologically and histologically similar to human MM tumors, and respond to treatments used for MM patients. Our system largely recapitulates human mesothelioma, and we advocate its use for the study of MM development and treatment. Malignant Mesothelioma is a highly aggressive cancer, which is difficult to diagnose and treat. Here we describe the molecular, cellular and morphological characterization of a syngeneic system consisting of murine AB1, AB12 and AB22 mesothelioma cells injected in immunocompetent BALB/c mice, which allows the study of the interplay of tumor cells with the immune system. Murine mesothelioma cells, like human ones, respond to exogenous High Mobility Group Box 1 protein, a Damage-Associated Molecular Pattern that acts as a chemoattractant for leukocytes and as a proinflammatory mediator. The tumors derived from AB cells are morphologically and histologically similar to human MM tumors, and respond to treatments used for MM patients. Our system largely recapitulates human mesothelioma, and we advocate its use for the study of MM development and treatment
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- 2016
45. General population low-count CLL-like MBL persists over time without clinical progression, although carrying the same cytogenetic abnormalities of CLL
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Antonis Dagklis, Lorenza Pecciarini, Agnieszka Janus, Francesca Cottini, Paolo Ghia, Cinzia Sala, Daniela Toniolo, Lydia Scarfò, Federico Caligaris-Cappio, Cristina Scielzo, Claudia Fazi, Anna Talarico, Fazi, C, Scarfò, L, Pecciarini, L, Cottini, F, Dagklis, A, Janus, A, Talarico, A, Scielzo, C, Sala, C, Toniolo, D, CALIGARIS CAPPIO, Federico, and Ghia, PAOLO PROSPERO
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Adult ,Male ,Lymphocytosis ,Receptors, Antigen, T-Cell, alpha-beta ,T-Lymphocytes ,Chronic lymphocytic leukemia ,Immunology ,Population ,chemical and pharmacologic phenomena ,Biology ,Biochemistry ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Humans ,Lymphocyte Count ,education ,In Situ Hybridization, Fluorescence ,Aged ,Aged, 80 and over ,Chromosome Aberrations ,B-Lymphocytes ,education.field_of_study ,Chromosomes, Human, Pair 12 ,Chromosomes, Human, Pair 13 ,Cell Biology ,Hematology ,Middle Aged ,Flow Cytometry ,bacterial infections and mycoses ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,V(D)J Recombination ,Leukemia ,Monoclonal ,Disease Progression ,Chromosome abnormality ,Monoclonal B-cell lymphocytosis ,Female ,medicine.symptom ,CD5 ,Chromosomes, Human, Pair 17 ,Follow-Up Studies - Abstract
Monoclonal B-cell lymphocytosis (MBL) is classified as chronic lymphocytic leukemia (CLL)–like, atypical CLL, and CD5− MBL. The number of B cells per microliter divides CLL-like MBL into MBL associated with lymphocytosis (usually detected in a clinical setting) and low-count MBL detected in the general population (usually identified during population screening). After a median follow-up of 34 months we reevaluated 76 low-count MBLs with 5-color flow cytometry: 90% of CLL-like MBL but only 44.4% atypical CLL and 66.7% CD5− MBL persisted over time. Population-screening CLL-like MBL had no relevant cell count change, and none developed an overt leukemia. In 50% of the cases FISH showed CLL-related chromosomal abnormalities, including monoallelic or biallelic 13q deletions (43.8%), trisomy 12 (1 case), and 17p deletions (2 cases). The analysis of the T-cell receptor β (TRBV) chains repertoire showed the presence of monoclonal T-cell clones, especially among CD4highCD8low, CD8highCD4low T cells. TRBV2 and TRBV8 were the most frequently expressed genes. This study indicates that (1) the risk of progression into CLL for low-count population-screening CLL-like MBL is exceedingly rare and definitely lower than that of clinical MBL and (2) chromosomal abnormalities occur early in the natural history and are possibly associated with the appearance of the typical phenotype.
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- 2011
46. Chlamydophila psittaciis viable and infectious in the conjunctiva and peripheral blood of patients with ocular adnexal lymphoma: Results of a single‐center prospective case–control study
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Antonio Giordano Resti, S. Magnino, Lorenza Pecciarini, Riccardo Dolcetti, Lucia Malabarba, Maria Giulia Cangi, Maurilio Ponzoni, Elisa Pasini, Nadia Vicari, G.P. Dognini, Andrés J.M. Ferreri, Silvano Rossini, Claudio Doglioni, Ferreri, Ajm, Dolcetti, R, Dognini, Gp, Malabarba, L, Vicari, N, Pasini, E, Ponzoni, Maurilio, Cangi, Mg, Pecciarini, L, Resti, Ag, Doglioni, Claudio, Rossini, S, and Magnino, S.
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Adult ,DNA, Bacterial ,Male ,Conjunctival Neoplasm ,Cancer Research ,Conjunctiva ,Conjunctival Neoplasms ,Polymerase Chain Reaction ,Peripheral blood mononuclear cell ,Ocular Adnexal Lymphoma ,Risk Factors ,Occupational Exposure ,medicine ,Humans ,Prospective Studies ,Animal Husbandry ,Aged ,Aged, 80 and over ,Chlamydia psittaci ,Infectivity ,biology ,business.industry ,MALT lymphoma ,Environmental Exposure ,Lymphoma, B-Cell, Marginal Zone ,Environmental exposure ,Chlamydia Infections ,Middle Aged ,Conjunctivitis ,biology.organism_classification ,medicine.disease ,medicine.anatomical_structure ,Chlamydophila psittaci ,Oncology ,Case-Control Studies ,Chronic Disease ,Immunology ,Leukocytes, Mononuclear ,Orbital Neoplasms ,Female ,business - Abstract
Ocular adnexal MALT lymphoma (OAML) is linked to Chlamydophila psittaci (Cp) infection. Viability and infectivity of Cp, demonstrated by growth in culture, has not been yet investigated in these patients. We conducted a single-center prospective case-control study to assess the prevalence, viability and infectivity of Cp in 20 OAML patients and 42 blood donors registered in a 6-month period. The presence of Cp in conjunctival swabs and peripheral blood mononuclear cells (PBMC) of patients and donors was assessed by TETR-PCR and in vitro cultures. From an epidemiological point of view, OAML patients often resided in rural areas, and reported a history of chronic conjunctivitis and prolonged contact with household animals (85% vs. 38% of donors; p = 0.00001). Cp was detected in lymphoma tissue in 15 (75%) patients. Cp DNA was detected in conjunctival swabs and/or PBMC from 10 (50%) patients and in PBMC from 1 (2%) donor (p = 0.01). Viability and infectivity of Cp, demonstrated by growth in culture, were confirmed in conjunctival swabs and/or PBMC from 5 (25%) patients, but not in donors (p = 0.002). This prospective study demonstrates, for the first time, that Cp present in the conjunctiva and PBMC of OAML patients is capable to grow and be isolated in cell cultures. Cp infection is common in OAML patients and exceptional in blood donors. Epidemiological data of OAML patients (prolonged contact with household animals and chronic conjunctivitis) are consistent with Cp exposure risk. (C) 2008 Wiley-Liss, Inc. Ocular adnexal MALT lymphoma (OAML) is linked to Chlamydophila psittaci (Cp) infection. Viability and infectivity of Cp, demonstrated by growth in culture, has not been yet investigated in these patients. We conducted a single-center prospective case-control study to assess the prevalence, viability and infectivity of Cp in 20 OAML patients and 42 blood donors registered in a 6-month period. The presence of Cp in conjunctival swabs and peripheral blood mononuclear cells (PBMC) of patients and donors was assessed by TETR-PCR and in vitro cultures. From an epidemiological point of view, OAML patients often resided in rural areas, and reported a history of chronic conjunctivitis and prolonged contact with household animals (85% vs. 38% of donors; p = 0.00001). Cp was detected in lymphoma tissue in 15 (75%) patients. Cp DNA was detected in conjunctival swabs and/or PBMC from 10 (50%) patients and in PBMC from 1 (2%) donor (p = 0.01). Viability and infectivity of Cp, demonstrated by growth in culture, were confirmed in conjunctival swabs and/or PBMC from 5 (25%) patients, but not in donors (p = 0.002). This prospective study demonstrates, for the first time, that Cp present in the conjunctiva and PBMC of OAML patients is capable to grow and be isolated in cell cultures. Cp infection is common in OAML patients and exceptional in blood donors. Epidemiological data of OAML patients (prolonged contact with household animals and chronic conjunctivitis) are consistent with Cp exposure risk. (C) 2008 Wiley-Liss, Inc.
- Published
- 2008
47. Characterization of t(6;11)(p21;q12) in a renal-cell carcinoma of an adult patient
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Claudio Doglioni, Ettore Macrì, Crocifissa Lo Cunsolo, Lorenza Pecciarini, Guido Martignoni, Elena Dal Cin, M. Giulia Cangi, Pecciarini, L, Cangi, Mg, LO CUNSOLO, C, Macri', E, DAL CIN, E, Martignoni, G, and Doglioni, Claudio
- Subjects
Cancer Research ,Molecular Sequence Data ,Chromosomal translocation ,Biology ,Polymerase Chain Reaction ,Translocation, Genetic ,Fusion gene ,Renal cell carcinoma ,Genetics ,medicine ,Carcinoma ,Humans ,Amino Acid Sequence ,Carcinoma, Renal Cell ,In Situ Hybridization, Fluorescence ,DNA Primers ,Base Sequence ,Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ,Chromosomes, Human, Pair 11 ,Helix-Loop-Helix Motifs ,breakpoint cluster region ,Chromosome Mapping ,Chromosome ,Middle Aged ,medicine.disease ,Molecular biology ,Fusion protein ,Kidney Neoplasms ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Karyotyping ,TFEB ,Chromosomes, Human, Pair 6 ,Female ,Gene Fusion - Abstract
Renal-cell carcinoma (RCC) constitutes a heterogeneous group of tumors with specific chromosome aberrations. Recently, a new small group of RCC, occurring in children and young adults, has been described as characterized by t(6;11)(p21;q12). It has been shown that this translocation results in the fusion of the 5′ portion of the ALPHA gene (11q12) with the transcription factor gene TFEB (6p21). Herewith, we report the first complete cytogenetic and molecular characterization of a t(6;11)-positive RCC of an adult patient, a 54-year-old woman. The tumor was histologically defined as RCC with peculiar features and it was negative for epithelial markers and positive for melanocytic markers. Chromosome QFQ banding analysis of short-term cultured cells from the RCC showed t(6;11)(p21;q12) as the sole cytogenetic abnormality. The translocation was confirmed by FISH analysis. RT-PCR analysis, performed on total RNA isolated from both neoplastic and normal tissue samples, revealed an ALPHA–TFEB chimeric transcript in the tumor sample; sequencing of the RT-PCR product defined a novel TFEB gene breakpoint cluster region, broader than the one reported thus far. Western blot analysis showed a band at the expected size of wild-type TFEB in the neoplastic tissue compared to the normal sample, supporting that the fusion gene does not encode for a chimeric protein but it causes an upregulation of the wild-type TFEB. Our data contribute to define better this rare RCC type, which is typical not only of childhood but can also be found in adulthood. © 2007 Wiley-Liss, Inc.
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- 2007
48. Uterine inflammatory myofibroblastic tumor in a 10-year-old girl presenting as polypoid mass
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Lorenza Pecciarini, Paolo Scollo, Maurilio Ponzoni, Paolo Amico, Giuseppe Pelosi, Filippo Fraggetta, Massimo Ippolito, Claudio Doglioni, Fraggetta, F, Doglioni, C, Scollo, P, Pecciarini, L, Ippolito, M1, Amico, P, Pelosi, G, and Ponzoni, Maurilio
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Inflammation ,Cancer Research ,medicine.medical_specialty ,business.industry ,media_common.quotation_subject ,Dermatology ,Immunohistochemistry ,Diagnosis, Differential ,Neoplasms, Muscle Tissue ,Polyps ,Oncology ,Lymphatic Metastasis ,Uterine Neoplasms ,medicine ,Biomarkers, Tumor ,Humans ,Female ,Girl ,business ,Child ,Watchful Waiting ,media_common - Published
- 2015
49. A 'twist box' code of p53 inactivation: twist box: p53 interaction promotes p53 degradation
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Lorenza Pecciarini, Sara Piccinin, Sabrina Rossi, Camillo Rosano, Flavia Pivetta, Angelo Paolo Dei Tos, Sara Sessa, Claudio Doglioni, Alessandra Grizzo, Elena Tonin, Lucia Zanatta, Maura Sonego, Roberta Maestro, Silvia Demontis, Piccinin, S, Tonin, E, Sessa, S, Demontis, S, Rossi, S, Pecciarini, L, Zanatta, L, Pivetta, F, Grizzo, A, Sonego, M, Rosano, C, Dei Tos, Ap, Doglioni, Claudio, and Maestro, R.
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Cancer Research ,Epithelial-Mesenchymal Transition ,animal structures ,DNA Copy Number Variations ,Mice, Nude ,Biology ,Tp53 mutation ,Mice ,medicine ,Animals ,Humans ,Phosphorylation ,RNA, Small Interfering ,Twist ,Genetics ,C-terminus ,Twist-Related Protein 1 ,Nuclear Proteins ,Proto-Oncogene Proteins c-mdm2 ,Sarcoma ,Cell Biology ,Cancer treatment ,Cell biology ,Repressor Proteins ,Cell Transformation, Neoplastic ,Mechanism of action ,Oncology ,biology.protein ,Mdm2 ,RNA Interference ,Cancer development ,Tumor Suppressor Protein p53 ,medicine.symptom - Abstract
Twist proteins have been shown to contribute to cancer development and progression by impinging on different regulatory pathways, but their mechanism of action is poorly defined. By investigating the role of Twist in sarcomas, we found that Twist1 acts as a mechanism alternative to TP53 mutation and MDM2 overexpression to inactivate p53 in mesenchymal tumors. We provide evidence that Twist1 binds p53 C terminus through the Twist box. This interaction hinders key posttranslational modifications of p53 and facilitates its MDM2-mediated degradation. Our study suggests the existence of a Twist box code of p53 inactivation and provides the proof of principle that targeting the Twist box:p53 interaction might offer additional avenues for cancer treatment. Twist proteins have been shown to contribute to cancer development and progression by impinging on different regulatory pathways, but their mechanism of action is poorly defined. By investigating the role of Twist in sarcomas, we found that Twist1 acts as a mechanism alternative to TP53 mutation and MDM2 overexpression to inactivate p53 in mesenchymal tumors. We provide evidence that Twist1 binds p53 C terminus through the Twist box. This interaction hinders key posttranslational modifications of p53 and facilitates its MDM2-mediated degradation. Our study suggests the existence of a Twist box code of p53 inactivation and provides the proof of principle that targeting the Twist box:p53 interaction might offer additional avenues for cancer treatment.
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- 2012
50. Chlamydia infection and lymphomas: association beyond ocular adnexal lymphomas highlighted by multiple detection methods
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Elena Dal Cin, Maurilio Ponzoni, S. Magnino, Lorenza Pecciarini, Riccardo Dolcetti, Elisa Pasini, Stefano Grassi, Luciano Sacchi, Rosalba Stefano, Antonia A. Lettini, Massimo Guidoboni, Claudio Doglioni, Maria Giulia Cangi, Andrés J.M. Ferreri, Ponzoni, Maurilio, Ferreri, Ajm, Guidoboni, M, Lettini, Aa, Cangi, Mg, Pasini, E, Sacchi, L, Pecciarini, L, Grassi, S, Dal Cin, E, Stefano, R, Magnino, S, Dolcetti, R, and Doglioni, Claudio
- Subjects
DNA, Bacterial ,Cancer Research ,Pathology ,medicine.medical_specialty ,Lymphoma ,Immunofluorescence ,Eye neoplasm ,Polymerase Chain Reaction ,Monocytes ,medicine ,Humans ,Microdissection ,Chlamydia psittaci ,Chlamydia ,medicine.diagnostic_test ,biology ,Eye Neoplasms ,Macrophages ,MALT lymphoma ,Chlamydia Infections ,Psittacosis ,medicine.disease ,biology.organism_classification ,Oncology ,Chlamydophila psittaci ,Immunology ,Immunohistochemistry - Abstract
Purpose: Chlamydia psittaci (Cp) has been associated to ocular adnexal lymphomas (OAL) with variable geographic distribution. Herein, we used multiple Chlamdia detection tools to identify Cp elementary bodies-containing cell and to assess Cp prevalence in both nodal and extranodal lymphomas. Experimental Design: TETR-PCR, immunohistochemistry, immunofluorescence, electron microscopy, and laser-capture microdissection were done in 35 OALs to define their effect in Chlamydia detection and, moreover, to identify the Cp cellular carrier. Cp prevalence was screened by TETR-PCR in 205 extraorbital lymphomas and 135 nonneoplastic controls. Results: Twenty-six (74%) OALs were associated with Cp infection: immunohistochemistry, immunofluorescence, and laser-capture microdissection-assisted PCR showed that monocytes/macrophages were the Cp carriers; electron microscopy showed the presence of intact CP elementary bodies into these cells. Immunohistochemistry and TETR-PCR showed a 70% concordance rate (P = 0.001). Cp DNA was equally prevalent in non-OAL, nodal, and extranodal lymphomas: among the latter, it was more common in diffuse large B-cell lymphomas of the skin (P = 0.03) and Waldeyer's ring. Conclusions: This multiparametric approach shows, for the first time, that monocytes/macrophages are the carriers of Cp, Cp seems preferentially associated with lymphomas arising in organs primarily exposed to antigens. The clinical implications of these findings deserve to be prospectively investigated. Purpose: Chlamydia psittaci (Cp) has been associated to ocular adnexal lymphomas (OAL) with variable geographic distribution. Herein, we used multiple Chlamdia detection tools to identify Cp elementary bodies-containing cell and to assess Cp prevalence in both nodal and extranodal lymphomas. Experimental Design: TETR-PCR, immunohistochemistry, immunofluorescence, electron microscopy, and laser-capture microdissection were done in 35 OALs to define their effect in Chlamydia detection and, moreover, to identify the Cp cellular carrier. Cp prevalence was screened by TETR-PCR in 205 extraorbital lymphomas and 135 nonneoplastic controls. Results: Twenty-six (74%) OALs were associated with Cp infection: immunohistochemistry, immunofluorescence, and laser-capture microdissection-assisted PCR showed that monocytes/macrophages were the Cp carriers; electron microscopy showed the presence of intact CP elementary bodies into these cells. Immunohistochemistry and TETR-PCR showed a 70% concordance rate (P = 0.001). Cp DNA was equally prevalent in non-OAL, nodal, and extranodal lymphomas: among the latter, it was more common in diffuse large B-cell lymphomas of the skin (P = 0.03) and Waldeyer's ring. Conclusions: This multiparametric approach shows, for the first time, that monocytes/macrophages are the carriers of Cp, Cp seems preferentially associated with lymphomas arising in organs primarily exposed to antigens. The clinical implications of these findings deserve to be prospectively investigated. PURPOSE: Chlamydia psittaci (Cp) has been associated to ocular adnexal lymphomas (OAL) with variable geographic distribution. Herein, we used multiple Chlamydia detection tools to identify Cp elementary bodies-containing cell and to assess Cp prevalence in both nodal and extranodal lymphomas. EXPERIMENTAL DESIGN: TETR-PCR, immunohistochemistry, immunofluorescence, electron microscopy, and laser-capture microdissection were done in 35 OALs to define their effect in Chlamydia detection and, moreover, to identify the Cp cellular carrier. Cp prevalence was screened by TETR-PCR in 205 extraorbital lymphomas and 135 nonneoplastic controls. RESULTS: Twenty-six (74%) OALs were associated with Cp infection: immunohistochemistry, immunofluorescence, and laser-capture microdissection-assisted PCR showed that monocytes/macrophages were the Cp carriers; electron microscopy showed the presence of intact Cp elementary bodies into these cells. Immunohistochemistry and TETR-PCR showed a 70% concordance rate (P = 0.001). Cp DNA was equally prevalent in non-OAL, nodal, and extranodal lymphomas: among the latter, it was more common in diffuse large B-cell lymphomas of the skin (P = 0.03) and Waldeyer's ring. CONCLUSIONS: This multiparametric approach shows, for the first time, that monocytes/macrophages are the carriers of Cp, Cp seems preferentially associated with lymphomas arising in organs primarily exposed to antigens. The clinical implications of these findings deserve to be prospectively investigated.
- Published
- 2008
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