95 results on '"Desantis V"'
Search Results
2. Folates dysmetabolism promotes atrial cardiomyopathy/fibrillation through a cardiac-bone marrow networking involving endothelial progenitor cell dysfunction and erythropoiesis diversion
- Author
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Sgarra, L, primary, Caccavo, VP, additional, Katsouras, G, additional, Di Monaco, A, additional, Quadrini, F, additional, Vitulano, N, additional, Troisi, F, additional, Solimando, A, additional, Cicco, S, additional, Nacci, C, additional, Potenza, MA, additional, Desantis, V, additional, Vacca, A, additional, Montagnani, M, additional, and Grimaldi, M, additional
- Published
- 2022
- Full Text
- View/download PDF
3. Neoformazione osteolitica ed esofitica mandibolare = Mandibular osteolytic and exophytic mass
- Author
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Pispero, A., Franchini, R., Sacilotto, G., Desantis, V., and Lombardi, N.
- Subjects
Oral surgery ,GCG intraosseous ,Giant-cell granuloma ,Osteolytic lesion ,Settore MED/28 - Malattie Odontostomatologiche ,Oral medicine - Published
- 2022
4. Accuracy comparison between the three-dimensional position of planned and placed implants with flapless fully-guided surgery: 1-year follow-up from a single-cohort retrospective study
- Author
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Passarelli, Pier Carmine, Ferro, M., De Angelis, Paolo, Papi, P., Piccirillo, G. B., Desantis, V., Papa, R., Pompa, G., and D'Addona, Antonio
- Subjects
Settore MED/28 - MALATTIE ODONTOSTOMATOLOGICHE ,Flapless surgery ,Dental implants ,Computer-guided implant dentistry ,Guided surgery - Published
- 2020
5. Study of cellular toxicity in vitro of two resins for orthodontic use
- Author
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Passarelli, Pier Carmine, Saccomanno, Sabina, De Angelis, Paolo, Romeo, Antonino, Piccirillo, G. B., Desantis, V., Grippaudo, Cristina, and D'Addona, Antonio
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Settore MED/28 - MALATTIE ODONTOSTOMATOLOGICHE ,citotoxicity ,composites - Published
- 2020
6. Quality of Life of Patients with Mandibular Third Molars and Mild Pericoronitis. A Comparison between Two Different Treatments: Extraction or Periodontal Approach
- Author
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Passarelli, P. C., primary, Lopez, M. A., additional, Desantis, V., additional, Piccirillo, G. B., additional, Rella, E., additional, Giovannini, V., additional, Speranza, A., additional, De Leonardis, M., additional, Manicone, P. F., additional, Casale, M., additional, and D’Addona, A., additional
- Published
- 2020
- Full Text
- View/download PDF
7. Autophagy: A New Mechanism of Prosurvival and Drug Resistance in Multiple Myeloma
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Desantis, V., primary, Saltarella, I., additional, Lamanuzzi, A., additional, Mariggiò, M.A., additional, Racanelli, V., additional, Vacca, Angelo, additional, and Frassanito, M.A., additional
- Published
- 2018
- Full Text
- View/download PDF
8. DARPin® molecule MP0250, a new antiangiogenic drug in multiple myeloma: An in vitro and in vivo study
- Author
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De Veirman, Kim, Rao, Luigia, Frassanito, Ma, Desantis, V, Giannico, D, Di Marzo, L., Fiedler, U, Harstrick, A, Ribatti, D., Vanderkerken, Karin, Vacca, Angelo, Hematology, Basic (bio-) Medical Sciences, and Faculty of Medicine and Pharmacy
- Subjects
multiple myeloma ,angiogenesis - Published
- 2017
9. Study of cellular toxicity in vitro of two resins for orthodontic use.
- Author
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PASSARELLI, P. C., SACCOMANNO, S., DE ANGELIS, P., ROMEO, A., PICCIRILLO, G. B., DESANTIS, V., GRIPPAUDO, C., and D'ADDONA, A.
- Abstract
OBJECTIVE: The objective of this work is to compare cellular toxicity in vitro of two resins for orthodontic use: an auto-polymerizable composite and a photo-polymerizable composite. MATERIALS AND METHODS: Samples were obtained by joining a couple of steel orthodontic brackets by using auto-polymerizing or photo-polymerizing resin. We used a halogen lamp, a mini LED lamp and a fast LED lamp used for orthodontics cure for 40 seconds. The 3T3 Swiss cellular line of fibroblasts was used. The samples obtained were used to determine the cellular toxicity in vitro using the Neutral Red Up-take (NRU) and the 3-(4,5-dimethylthiazol- 2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: Toxicity of the extract appraised at a low level at MTT and NRU assays. There were statistically relevant differences between the toxicity induced by the auto-polymerizing material and the toxicity induced by the photo-polymerizing composite material, polymerized with the blue-light lamp (p < 0.001) and with the mini LED lamp (p < 0.05). CONCLUSIONS: From the data collected in this study, we can conclude that both resins show a low level of cytotoxicity that, in the case of photochemical polymerizing resin, depends on the characteristics of the lamp. [ABSTRACT FROM AUTHOR]
- Published
- 2020
10. Belimumab restores Treg/Th17 balance in patients with refractory systemic lupus erythematosus
- Author
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Prete, M, primary, Leone, P, additional, Frassanito, M A, additional, Desantis, V, additional, Marasco, C, additional, Cicco, S, additional, Dammacco, F, additional, Vacca, A, additional, and Racanelli, V, additional
- Published
- 2018
- Full Text
- View/download PDF
11. JAM-A as a prognostic factor and new therapeutic target in multiple myeloma
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Solimando, A G, primary, Brandl, A, additional, Mattenheimer, K, additional, Graf, C, additional, Ritz, M, additional, Ruckdeschel, A, additional, Stühmer, T, additional, Mokhtari, Z, additional, Rudelius, M, additional, Dotterweich, J, additional, Bittrich, M, additional, Desantis, V, additional, Ebert, R, additional, Trerotoli, P, additional, Frassanito, M A, additional, Rosenwald, A, additional, Vacca, A, additional, Einsele, H, additional, Jakob, F, additional, and Beilhack, A, additional
- Published
- 2017
- Full Text
- View/download PDF
12. Some limits of the method of the diffraction hyperbolas and a proposal for its overcoming
- Author
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Persico, R., primary, Matera, L., additional, Desantis, V., additional, Congedo, F., additional, Lambot, S., additional, and Got, J. B., additional
- Published
- 2016
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13. Halting pro-survival autophagy by TGFβ inhibition in bone marrow fibroblasts overcomes bortezomib resistance in multiple myeloma patients
- Author
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Frassanito, M A, primary, De Veirman, K, additional, Desantis, V, additional, Marzo, L Di, additional, Vergara, D, additional, Ruggieri, S, additional, Annese, T, additional, Nico, B, additional, Menu, E, additional, Catacchio, I, additional, Ria, R, additional, Racanelli, V, additional, Maffia, M, additional, Angelucci, E, additional, Derudas, D, additional, Fumarulo, R, additional, Dammacco, F, additional, Ribatti, D, additional, Vanderkerken, K, additional, and Vacca, A, additional
- Published
- 2015
- Full Text
- View/download PDF
14. LIVELLI SIERICI DI VITAMINA D IN PAZIENTI CON IPERTENSIONE ARTRIOSA DI 1 GRADO
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Polidoro, L, Struglia, M, Desantis, V, Scipioni, R, DEL PINTO, R, Casale, R, Properzi, Giuliana, and Ferri, Claudio
- Published
- 2011
15. JAM-A as a prognostic factor and new therapeutic target in multiple myeloma
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Solimando, A G, Brandl, A, Mattenheimer, K, Graf, C, Ritz, M, Ruckdeschel, A, Stühmer, T, Mokhtari, Z, Rudelius, M, Dotterweich, J, Bittrich, M, Desantis, V, Ebert, R, Trerotoli, P, Frassanito, M A, Rosenwald, A, Vacca, A, Einsele, H, Jakob, F, and Beilhack, A
- Abstract
Cell adhesion in the multiple myeloma (MM) microenvironment has been recognized as a major mechanism of MM cell survival and the development of drug resistance. Here we addressed the hypothesis that the protein junctional adhesion molecule-A (JAM-A) may represent a novel target and a clinical biomarker in MM. We evaluated JAM-A expression in MM cell lines and in 147 MM patient bone marrow aspirates and biopsies at different disease stages. Elevated JAM-A levels in patient-derived plasma cells were correlated with poor prognosis. Moreover, circulating soluble JAM-A (sJAM-A) levels were significantly increased in MM patients as compared with controls. Notably, in vitro JAM-A inhibition impaired MM migration, colony formation, chemotaxis, proliferation and viability. In vivo treatment with an anti-JAM-A monoclonal antibody (aJAM-A moAb) impaired tumor progression in a murine xenograft MM model. These results demonstrate that therapeutic targeting of JAM-A has the potential to prevent MM progression, and lead us to propose JAM-A as a biomarker in MM, and sJAM-A as a serum-based marker for clinical stratification.
- Published
- 2018
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- View/download PDF
16. Fetal MR Imaging
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D'Aprile, P., primary, Strada, A., additional, Tarantino, A., additional, Daddario, V., additional, Marotta, V., additional, Aquilino, P., additional, Desantis, V., additional, Brindicci, D., additional, and Girard, N., additional
- Published
- 2004
- Full Text
- View/download PDF
17. Step-feed operation at short detention times – a cost effective method for improving wastewater treatment
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Adamski, R.E., primary, DeSantis, V., additional, Spangel, A., additional, Pynn, J., additional, Betty, L., additional, Koch, C.M., additional, and Gyory, S.A., additional
- Published
- 2000
- Full Text
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18. America and Europe, 1775-1992
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DeSantis, V. P., primary
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- 1992
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19. Fetal MR Imaging
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D'Aprile, P., Strada, A., Tarantino, A., Daddario, V., Marotta, V., Aquilino, P., Desantis, V., Brindicci, D., and Girard, N.
- Abstract
Although sonography (US) is the first imaging technique for evaluating the developing fetus, significant limitations exist in the sonographic prenatal diagnosis of many brain disorders and in the evaluation of cerebral anatomy. At present, the role of MR imaging in the diagnosis of prenatal anomalies is confined to determining the underlying cause of non-specific fetal abnormalities detected sonographically, especially in fetal brain malformations, or when US is equivocal or limited. In particular, the major indication for MR study is ventriculomegaly, because this sign could be associated with different anomalies (malformations, ischemic disease and cerebral destructive lesions); other indications for MRI include maternal infections and genetic syndromes. MR imaging is an important adjunctive tool for prenatal imaging in those instances where complex anomalies are suspected by US, when fetal surgery is contemplated, or when a definitive diagnosis cannot be determined. In this work we report our experience of fetal MRI in fetuses with suspect cerebral anomalies previously detected by US.
- Published
- 2004
- Full Text
- View/download PDF
20. How frequent are postoperative complications after an impacted mandibular third molar extraction?
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Passarelli, P. C., Rella, E., Piccirillo, G. B., Desantis, V., Giovannini, V., Speranza, A., Leonardis, M., Papi, P., Pompa, G., Paolo Francesco Manicone, and D’addona, A.
- Subjects
Settore MED/28 - MALATTIE ODONTOSTOMATOLOGICHE ,Pain, Postoperative ,Postoperative Complications ,complications ,Tooth Extraction ,Tooth, Impacted ,extraction ,Humans ,Molar, Third ,Mandible ,third molar ,Molar ,oral surgery
21. Evaluation of the periodontal healing of the second mandibular molar distal site following insertion of PRF in the third molar post extraction alveolus
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Passarelli, P. C., Antonino Romeo, Lopez, M. A., Angelis, P., Desantis, V., Piccirillo, G. B., Papa, R., Papi, P., Pompa, G., Moffa, A., Casale, M., and D’addona, A.
- Subjects
Settore MED/28 - MALATTIE ODONTOSTOMATOLOGICHE ,Settore MED/29 - CHIRURGIA MAXILLOFACCIALE ,Platelet-rich fibrin
22. Targeting the immune microenvironment in Waldenström Macroglobulinemia via halting the CD40/CD40-ligand axis
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Antonio Sacco, Vanessa Desantis, Jon Celay, Viviana Giustini, Fabio Rigali, Francesco D Savino, Michele Cea, Debora Soncini, Antonia Cagnetta, Antonio Giovanni Solimando, Deborah D'Aliberti, Silvia Spinelli, Daniele Ramazzotti, Camillo Almici, Katia Todoerti, Antonino Neri, Antonella Anastasia, Alessandra Tucci, Marina Motta, Marco Chiarini, Yawara Kawano, Jose-Al Martinez-Climent, Rocco Piazza, Aldo M Roccaro, Sacco, A, Desantis, V, Celay, J, Giustini, V, Rigali, F, Savino, F, Cea, M, Soncini, D, Cagnetta, A, Solimando, A, D'Aliberti, D, Spinelli, S, Ramazzotti, D, Almici, C, Todoerti, K, Neri, A, Anastasia, A, Tucci, A, Motta, M, Chiarini, M, Kawano, Y, Martinez-Climent, J, Piazza, R, and Roccaro, A
- Subjects
Immunology ,Cell Biology ,Hematology ,Waldenström Macroglobulinemia ,Biochemistry - Abstract
Recent investigations have improved our understanding of the molecular aberrations supporting Waldenström macroglobulinemia (WM) biology; however, whether the immune microenvironment contributes to WM pathogenesis remains unanswered. First, we showed how a transgenic murine model of human-like lymphoplasmacytic lymphoma/WM exhibits an increased number of regulatory T cells (Tregs) relative to control mice. These findings were translated into the WM clinical setting, in which the transcriptomic profiling of Tregs derived from patients with WM unveiled a peculiar WM-devoted messenger RNA signature, with significant enrichment for genes related to nuclear factor κB–mediated tumor necrosis factor α signaling, MAPK, and PI3K/AKT, which was paralleled by a different Treg functional phenotype. We demonstrated significantly higher Treg induction, expansion, and proliferation triggered by WM cells, compared with their normal cellular counterpart; with a more profound effect within the context of CXCR4C1013G-mutated WM cells. By investigating the B-cell–to–T-cell cross talk at single-cell level, we identified the CD40/CD40-ligand as a potentially relevant axis that supports WM cell–Tregs interaction. Our findings demonstrate the existence of a Treg-mediated immunosuppressive phenotype in WM, which can be therapeutically reversed by blocking the CD40L/CD40 axis to inhibit WM cell growth.
- Published
- 2023
23. Art. 11 Decisione sulle questioni di giurisdizione
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SQUAZZONI, A, Allena, M, Avanzini, G, Averardi, A: Bartolini, A, Berti, N, Biancardi, B, Bombardelli, M, Boschetti, B, Calabrò, M, Calegari, A, Caranta, R, Carruccio, L, Cassatella, A, Corvaja, F, Cusenza, G, De Goetzen, S, De Lucia, L, Del Gatto, S, Delsignore, M, Desantis, V, Ferrazzi, C, Figorilli, F, Franca, S, Giannelli, A, Giardino, E, Giusti, A, Magliari, A, Manganaro, F, Mannucci, G, Marcovecchio, A, Marra, A, Mazzarolli, L, Micchiché, C, Midiri, F, Mirate, S, Occhiena, M, Pantalone, P, Parona, L, Pellizzari, S, Piazza, I, Piscitelli, L, Police, A, Posteraro, N, Primerano, G, Ramajoli, M, Renna, M, Romeo, A, Saitta, F, Sessa, V, Silvestri, M, Simonati, A, Squazzoni, A, Taccogna, G, Tonoletti, B, Torchia, L, Tropea, G, Vaccari, S, Valaguzza, S, Vernile, S, Falcon, G, Cortese, F, and Marchetti, B
- Subjects
translatio iudicii - Published
- 2021
24. Art. 8 Cognizione incidentale e questioni pregiudiziali
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SQUAZZONI, A, Allena, M, Avanzini, G, Averardi, A: Bartolini, A, Berti, N, Biancardi, B, Bombardelli, M, Boschetti, B, Calabrò, M, Calegari, A, Caranta, R, Carruccio, L, Cassatella, A, Corvaja, F, Cusenza, G, De Goetzen, S, De Lucia, L, Del Gatto, S, Delsignore, M, Desantis, V, Ferrazzi, C, Figorilli, F, Franca, S, Giannelli, A, Giardino, E, Giusti, A, Magliari, A, Manganaro, F, Mannucci, G, Marcovecchio, A, Marra, A, Mazzarolli, L, Micchiché, C, Midiri, F, Mirate, S, Occhiena, M, Pantalone, P, Parona, L, Pellizzari, S, Piazza, I, Piscitelli, L, Police, A, Posteraro, N, Primerano, G, Ramajoli, M, Renna, M, Romeo, A, Saitta, F, Sessa, V, Silvestri, M, Simonati, A, Squazzoni, A, Taccogna, G, Tonoletti, B, Torchia, L, Tropea, G, Vaccari, S, Valaguzza, S, Vernile, S, Falcon, G, Cortese, F, and Marchetti, B
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cognizione incidentale questioni pregiudiziali ,IUS/10 - DIRITTO AMMINISTRATIVO - Published
- 2021
25. Art. 10 Regolamento preventivo di giurisdizione
- Author
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SQUAZZONI, A, Allena, M, Avanzini, G, Averardi, A: Bartolini, A, Berti, N, Biancardi, B, Bombardelli, M, Boschetti, B, Calabrò, M, Calegari, A, Caranta, R, Carruccio, L, Cassatella, A, Corvaja, F, Cusenza, G, De Goetzen, S, De Lucia, L, Del Gatto, S, Delsignore, M, Desantis, V, Ferrazzi, C, Figorilli, F, Franca, S, Giannelli, A, Giardino, E, Giusti, A, Magliari, A, Manganaro, F, Mannucci, G, Marcovecchio, A, Marra, A, Mazzarolli, L, Micchiché, C, Midiri, F, Mirate, S, Occhiena, M, Pantalone, P, Parona, L, Pellizzari, S, Piazza, I, Piscitelli, L, Police, A, Posteraro, N, Primerano, G, Ramajoli, M, Renna, M, Romeo, A, Saitta, F, Sessa, V, Silvestri, M, Simonati, A, Squazzoni, A, Taccogna, G, Tonoletti, B, Torchia, L, Tropea, G, Vaccari, S, Valaguzza, S, Vernile, S, Falcon, G, Cortese, F, and Marchetti, B
- Subjects
regolamento giurisdizione ,IUS/10 - DIRITTO AMMINISTRATIVO - Published
- 2021
26. Art. 9 Difetto di giurisdizione
- Author
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Squazzoni, A, Allena, M, Avanzini, G, Averardi, A: Bartolini, A, Berti, N, Biancardi, B, Bombardelli, M, Boschetti, B, Calabrò, M, Calegari, A, Caranta, R, Carruccio, L, Cassatella, A, Corvaja, F, Cusenza, G, De Goetzen, S, De Lucia, L, Del Gatto, S, Delsignore, M, Desantis, V, Ferrazzi, C, Figorilli, F, Franca, S, Giannelli, A, Giardino, E, Giusti, A, Magliari, A, Manganaro, F, Mannucci, G, Marcovecchio, A, Marra, A, Mazzarolli, L, Micchiché, C, Midiri, F, Mirate, S, Occhiena, M, Pantalone, P, Parona, L, Pellizzari, S, Piazza, I, Piscitelli, L, Police, A, Posteraro, N, Primerano, G, Ramajoli, M, Renna, M, Romeo, A, Saitta, F, Sessa, V, Silvestri, M, Simonati, A, Squazzoni, A, Taccogna, G, Tonoletti, B, Torchia, L, Tropea, G, Vaccari, S, Valaguzza, S, Vernile, S, Falcon, G, Cortese, F, and Marchetti, B
- Subjects
difetto giurisdizione ,IUS/10 - DIRITTO AMMINISTRATIVO - Published
- 2021
27. Halting pro-survival autophagy by TGFβ inhibition in bone marrow fibroblasts overcomes bortezomib resistance in multiple myeloma patients
- Author
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F. Dammacco, Maria Antonia Frassanito, Domenico Ribatti, Vito Racanelli, K De Veirman, Ruggiero Fumarulo, Beatrice Nico, Ivana Catacchio, Vanessa Desantis, Simona Ruggieri, Michele Maffia, Angelo Vacca, Roberto Ria, Daniele Derudas, Daniele Vergara, Tiziana Annese, Emanuele Angelucci, L. Di Marzo, Eline Menu, Karin Vanderkerken, Hematology, Basic (bio-) Medical Sciences, Frassanito, Ma, De Veirman, K, Desantis, V, Di Marzo, L, Vergara, Daniele, Ruggieri, S, Annese, T, Nico, B, Menu, E, Catacchio, I, Ria, R, Racanelli, V, Maffia, Michele, Angelucci, E, Derudas, D, Fumarulo, Ruggiero, Dammacco, F, Ribatti, D, Vanderkerken, K, and Vacca, Angelo
- Subjects
0301 basic medicine ,Male ,Cancer Research ,medicine.medical_treatment ,RNA-Binding Protein ,Pyrrole ,Antineoplastic Agent ,Bortezomib ,Bort ,Mice ,Transforming Growth Factor beta ,Drug Combination ,Aged, 80 and over ,biology ,TOR Serine-Threonine Kinase ,TOR Serine-Threonine Kinases ,RNA-Binding Proteins ,Hematology ,Middle Aged ,Gene Expression Regulation, Neoplastic ,Drug Combinations ,medicine.anatomical_structure ,Oncology ,Bone Marrow Cell ,Fibroblast ,Plasma Cell ,Female ,Survival Analysi ,Multiple Myeloma ,Microtubule-Associated Proteins ,medicine.drug ,Human ,Signal Transduction ,Xenograft Model Antitumor Assay ,Plasma Cells ,Primary Cell Culture ,Antineoplastic Agents ,Bone Marrow Cells ,03 medical and health sciences ,medicine ,Autophagy ,Animals ,Humans ,Pyrroles ,Aged ,Animal ,Growth factor ,Microtubule-Associated Protein ,Transforming growth factor beta ,Fibroblasts ,Molecular biology ,Survival Analysis ,Xenograft Model Antitumor Assays ,030104 developmental biology ,Apoptosis ,Drug Resistance, Neoplasm ,Pyrazole ,biology.protein ,Cancer research ,Pyrazoles ,Bone marrow ,Transforming growth factor - Abstract
Bortezomib (bort) has improved overall survival in patients with multiple myeloma (MM), but the majority of them develop drug resistance. In this study, we demonstrate that bone marrow (BM) fibroblasts (cancer-associated fibroblasts; CAFs) from bort-resistant patients are insensitive to bort and protect the RPMI8226 and patients' plasma cells against bort-induced apoptosis. Bort triggers CAFs to produce high levels of interleukin (IL)-6, IL-8, insulin-like growth factor (IGF)-1 and transforming growth factor (TGF) β. Proteomic studies on CAFs demonstrate that bort resistance parallels activation of oxidative stress and pro-survival autophagy. Indeed, bort induces reactive oxygen species in bort-resistant CAFs and activates autophagy by increasing light chain 3 protein (LC3)-II and inhibiting p62 and phospho-mammalian target of rapamycin. The small-interfering RNA knockdown of Atg7, and treatment with 3-methyladenine, restores bort sensitivity in bort-resistant CAFs and produces cytotoxicity in plasma cells co-cultured with CAFs. In the syngeneic 5T33 MM model, bort-treatment induces the expansion of LC3-II(+) CAFs. TGFβ mediates bort-induced autophagy, and its blockade by LY2109761, a selective TβRI/II inhibitor, reduces the expression of p-Smad2/3 and LC3-II and induces apoptosis in bort-resistant CAFs. A combination of bort and LY2109761 synergistically induces apoptosis of RPMI8226 co-cultured with bort-resistant CAFs. These data define a key role for CAFs in bort resistance of plasma cells and provide the basis for a novel targeted therapeutic approach.
- Published
- 2016
28. CARBONIZATION OF PLASTICS AND REFRACTORY MATERIALS RESEARCH. VOLUME II. REFRACTORY MATERIALS. Seventh Quarterly Progress Report, January 1, 1962-March 31, 1962
- Author
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DeSantis, V
- Published
- 1962
29. REFRACTORY MATERIALS RESEARCH. Ninth Quarterly Progress Report, October 1, 1962 to December 31, 1962
- Author
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DeSantis, V
- Published
- 1962
30. REFRACTORY MATERIALS RESEARCH
- Author
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DeSantis, V
- Published
- 1963
31. New Generation Customized Titanium Meshes for the Guided Bone Regeneration of Severe Alveolar Ridge Defects: Preliminary Results of a Retrospective Case Series.
- Author
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Ronda M, Desantis V, Bruno D, Veneriano L, Elli C, and Pispero A
- Published
- 2024
- Full Text
- View/download PDF
32. Decoding the Intricate Landscape of Pancreatic Cancer: Insights into Tumor Biology, Microenvironment, and Therapeutic Interventions.
- Author
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Argentiero A, Andriano A, Caradonna IC, de Martino G, and Desantis V
- Abstract
Pancreatic ductal adenocarcinoma (PDAC) presents significant oncological challenges due to its aggressive nature and poor prognosis. The tumor microenvironment (TME) plays a critical role in progression and treatment resistance. Non-neoplastic cells, such as cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), contribute to tumor growth, angiogenesis, and immune evasion. Although immune cells infiltrate TME, tumor cells evade immune responses by secreting chemokines and expressing immune checkpoint inhibitors (ICIs). Vascular components, like endothelial cells and pericytes, stimulate angiogenesis to support tumor growth, while adipocytes secrete factors that promote cell growth, invasion, and treatment resistance. Additionally, perineural invasion, a characteristic feature of PDAC, contributes to local recurrence and poor prognosis. Moreover, key signaling pathways including Kirsten rat sarcoma viral oncogene (KRAS), transforming growth factor beta (TGF-β), Notch, hypoxia-inducible factor (HIF), and Wnt/β-catenin drive tumor progression and resistance. Targeting the TME is crucial for developing effective therapies, including strategies like inhibiting CAFs, modulating immune response, disrupting angiogenesis, and blocking neural cell interactions. A recent multi-omic approach has identified signature genes associated with anoikis resistance, which could serve as prognostic biomarkers and targets for personalized therapy.
- Published
- 2024
- Full Text
- View/download PDF
33. Comprehensive analysis of clinical outcomes, infectious complications and microbiological data in newly diagnosed multiple myeloma patients: a retrospective observational study of 92 subjects.
- Author
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Desantis V, Borrelli P, Panebianco T, Fusillo A, Bochicchio D, Solito A, Pappagallo F, Mascolo A, Ancona A, Cicco S, Cerchione C, Romano A, Montagnani M, Ria R, Vacca A, and Solimando AG
- Subjects
- Humans, Retrospective Studies, Male, Female, Aged, Middle Aged, Italy epidemiology, Aged, 80 and over, Adult, Tertiary Care Centers, Multiple Myeloma complications, Multiple Myeloma microbiology, Sepsis microbiology
- Abstract
Patients with multiple myeloma (MM) have an increased risk of sepsis due to underlying disease- and treatment-related immunosuppression. However, data on sepsis incidence, causative pathogens, and impact on outcomes in newly diagnosed MM (NDMM) are limited. We conducted a retrospective observational study of 92 NDMM patients who developed sepsis between 2022 and 2023 at a tertiary care center in Italy. Patient characteristics, sepsis criteria [Quick Sequential Organ Failure Assessment, Systemic Inflammatory Response Syndrome (SIRS)], microbiology results, and associations with progression-free survival (PFS) were analyzed. In this cohort of 92 critically-ill patients, pathogenic organisms were identified via microbiological culture in 74 cases. However, among the remaining 18 culture-negative patients, 9 exhibited a SIRS score of 2 and another 9 had a SIRS score of 4, suggestive of a clinical presentation consistent with sepsis despite negative cultures. Common comorbidities included renal failure (60%), anemia (71%), and bone disease (83%). Gram-negative (28%) and Gram-positive (23%) bacteria were frequent causative organisms, along with fungi (20%). Cox Univariate analyses for PFS showed statically significant HR in patients with albumin ≥ 3.5 vs < 3.5 (HR = 5.04, p < 0.001), Karnofsky performance status ≥ 80 vs < 80 (HR = 2.01, p = 0.002), and early-stage vs late-stage disease by International Staging System (HR = 4.76 and HR = 12.52, both p < 0.001) and Revised International Staging System (R-ISS III vs R-ISS I, HR = 7.38, p < 0.001). Sepsis is common in NDMM and associated with poor outcomes. Risk stratification incorporating sepsis severity, comorbidities, and disease stage may help guide preventive strategies and optimize MM management., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
34. Navigating Lymphomas through BCR Signaling and Double-Hit Insights: Overview.
- Author
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Argentiero A, Andriano A, Marziliano D, and Desantis V
- Abstract
Non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of lymphoproliferative disorders originating from B, T, or NK lymphocytes. They represent approximately 4-5% of new cancer cases and are classified according to the revised WHO system based on cell lineage, morphology, immunophenotype, and genetics. Diagnosis requires adequate biopsy material, though integrated approaches are used for leukemic presentations. Molecular profiling is improving classification and identifying prognostic markers. Indolent NHLs, such as follicular lymphoma and marginal zone lymphoma, typically pursue a non-aggressive clinical course with long survival. Aggressive diffuse large B-cell lymphoma (DLBCL) is the most common subtype. Recent studies have elucidated pathogenic mechanisms like MYC translocations and BCR pathway mutations. "Double hit" lymphomas with MYC and BCL2/BCL6 alterations confer a poor prognosis. Treatment approaches are evolving, with chemoimmunotherapy remaining standard for many indolent cases while intensified regimens and targeted agents show promise for refractory or high-risk aggressive disease. Continued elucidation of the genetic and microenvironmental underpinnings of lymphomagenesis is critical for developing personalized therapeutic strategies.
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- 2024
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35. A Novel Automatic Algorithm to Support Lung Ultrasound Non-Expert Physicians in Interstitial Pneumonia Evaluation: A Single-Center Study.
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Marozzi MS, Cicco S, Mancini F, Corvasce F, Lombardi FA, Desantis V, Loponte L, Giliberti T, Morelli CM, Longo S, Lauletta G, Solimando AG, Ria R, and Vacca A
- Abstract
Introduction: Lung ultrasound (LUS) is widely used in clinical practice for identifying interstitial lung diseases (ILDs) and assessing their progression. Although high-resolution computed tomography (HRCT) remains the gold standard for evaluating the severity of ILDs, LUS can be performed as a screening method or as a follow-up tool post-HRCT. Minimum training is needed to better identify typical lesions, and the integration of innovative artificial intelligence (AI) automatic algorithms may enhance diagnostic efficiency., Aim: This study aims to assess the effectiveness of a novel AI algorithm in automatic ILD recognition and scoring in comparison to an expert LUS sonographer. The "SensUS Lung" device, equipped with an automatic algorithm, was employed for the automatic recognition of the typical ILD patterns and to calculate an index grading of the interstitial involvement., Methods: We selected 33 Caucasian patients in follow-up for ILDs exhibiting typical HRCT patterns (honeycombing, ground glass, fibrosis). An expert physician evaluated all patients with LUS on twelve segments (six per side). Next, blinded to the previous evaluation, an untrained operator, a non-expert in LUS, performed the exam with the SensUS device equipped with the automatic algorithm ("SensUS Lung") using the same protocol. Pulmonary functional tests (PFT) and DLCO were conducted for all patients, categorizing them as having reduced or preserved DLCO. The SensUS device indicated different grades of interstitial involvement named Lung Staging that were scored from 0 (absent) to 4 (peak), which was compared to the Lung Ultrasound Score (LUS score) by dividing it by the number of segments evaluated. Statistical analyses were done with Wilcoxon tests for paired values or Mann-Whitney for unpaired samples, and correlations were performed using Spearman analysis; p < 0.05 was considered significant., Results: Lung Staging was non-inferior to LUS score in identifying the risk of ILDs (median SensUS 1 [0-2] vs. LUS 0.67 [0.25-1.54]; p = 0.84). Furthermore, the grade of interstitial pulmonary involvement detected with the SensUS device is directly related to the LUS score (r = 0.607, p = 0.002). Lung Staging values were inversely correlated with forced expiratory volume at first second (FEV1%, r = -0.40, p = 0.027), forced vital capacity (FVC%, r = -0.39, p = 0.03) and forced expiratory flow (FEF) at 25th percentile (FEF25%, r = -0.39, p = 0.02) while results directly correlated with FEF25-75% (r = 0.45, p = 0.04) and FEF75% (r = 0.43, p = 0.01). Finally, in patients with reduced DLCO, the Lung Staging was significantly higher, overlapping the LUS (reduced median 1 [1-2] vs. preserved 0 [0-1], p = 0.001), and overlapping the LUS (reduced median 18 [4-20] vs. preserved 5.5 [2-9], p = 0.035)., Conclusions: Our data suggest that the considered AI automatic algorithm may assist non-expert physicians in LUS, resulting in non-inferior-to-expert LUS despite a tendency to overestimate ILD lesions. Therefore, the AI algorithm has the potential to support physicians, particularly non-expert LUS sonographers, in daily clinical practice to monitor patients with ILDs. The adopted device is user-friendly, offering a fully automatic real-time analysis. However, it needs proper training in basic skills.
- Published
- 2024
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36. The Complexity of the Tumor Microenvironment in Hepatocellular Carcinoma and Emerging Therapeutic Developments.
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Argentiero A, Delvecchio A, Fasano R, Andriano A, Caradonna IC, Memeo R, and Desantis V
- Abstract
This review explores various aspects of the HCC TME, including both cellular and non-cellular components, to elucidate their roles in tumor development and progression. Specifically, it highlights the significance of cancer-associated fibroblasts (CAFs) and their contributions to tumor progression, angiogenesis, immune suppression, and therapeutic resistance. Moreover, this review emphasizes the role of immune cells, such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and regulatory T-cells (Tregs), in shaping the immunosuppressive microenvironment that promotes tumor growth and immune evasion. Furthermore, we also focused only on the non-cellular components of the HCC TME, including the extracellular matrix (ECM) and the role of hypoxia-induced angiogenesis. Alterations in the composition of ECM and stiffness have been implicated in tumor invasion and metastasis, while hypoxia-driven angiogenesis promotes tumor growth and metastatic spread. The molecular mechanisms underlying these processes, including the activation of hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF) signaling, are also discussed. In addition to elucidating the complex TME of HCC, this review focuses on emerging therapeutic strategies that target the TME. It highlights the potential of second-line treatments, such as regorafenib, cabozantinib, and ramucirumab, in improving overall survival for advanced HCC patients who have progressed on or were intolerant to first-line therapy. Furthermore, this review explores the implications of the Barcelona Clinic Liver Cancer (BCLC) staging and classification system in guiding HCC management decisions. The BCLC system, which incorporates tumor stage, liver function, and performance status, provides a framework for treatment stratification and prognosis prediction in HCC patients. The insights gained from this review contribute to the development of novel therapeutic interventions and personalized treatment approaches for HCC patients, ultimately improving clinical outcomes in this challenging disease.
- Published
- 2023
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37. Changes in Lipids in Granulomatosis with Polyangiitis Relates to Glucocorticoids and History of Hypertension.
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Marozzi MS, Vacca A, Desantis V, Panebianco T, Catena C, Brosolo G, Noviello S, Cirulli A, Solimando AG, Sechi LA, Cicco S, and Ria R
- Abstract
Granulomatosis with polyangiitis (GPA) is an ANCA-associated small-vessel vasculitis. Vessel wall inflammation induces multiple vascular damages, leading to accelerated atherosclerosis. Metabolic profile and cardiovascular risk are somewhat understood in GPA patients. Cardiovascular atherosclerotic disease (ASCVD) may represent a risk for outcomes. Our purpose is to evaluate ASCVD risk in GPA patients. Thirty-six patients received GPA diagnosis (T0) and were evaluated after 1 (T1) and 2 (T2) years follow-up. All patients were treated with high-dose glucocorticoid, one-year tapered, along with immunosuppressants. Total cholesterol significantly increased in T1 vs. T0 and T2. LDL exhibited the same trend, while triglycerides increased in both T1 and T2 vs. T0. No difference was found in HDL. A significant hsCRP decrease was detected at T1 and T2 vs. T0, but not between T2 and T1. Moreover, we found a significant reduction in ESR at T2 compared with T1 and T0 and at T1 compared to T0. Hypertensive patients presented a pronounced increase in lipids, while inflammation reduced slowly compared to normotensives. Our data suggest that the increase in cholesterol and LDL in T1 is a consequence of glucocorticoids. These data can be useful in the evaluation of both CV diseases and lipid metabolism, which are closely related to vessel inflammation.
- Published
- 2023
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38. STAT1 overexpression triggers aplastic anemia: a pilot study unravelling novel pathogenetic insights in bone marrow failure.
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Solimando AG, Desantis V, Palumbo C, Marasco C, Pappagallo F, Montagnani M, Ingravallo G, Cicco S, Di Paola R, Tabares P, Beilhack A, Dammacco F, Ria R, and Vacca A
- Subjects
- Female, Humans, Adult, Pilot Projects, Janus Kinases metabolism, Prospective Studies, Signal Transduction, STAT Transcription Factors, STAT1 Transcription Factor genetics, STAT1 Transcription Factor metabolism, Anemia, Aplastic genetics, Pancytopenia
- Abstract
We identified STAT1 gain of function (GOF) in a 32-year-old female with pallor, weakness, cough, and dyspnea admitted to our Division of Medicine. She had severe oral ulcers (OU), type 1 diabetes (T1DM), and pancytopenia. Bone marrow (BM) biopsy showed the absence of erythroid precursors. Peripheral blood parameters such as neutrophils < 500/mL, reticulocytes < 2%, and BM hypo-cellularity allowed to diagnose severe aplastic anemia. A heterozygous variant (p.520T>C, p.Cys174Arg) of STAT1 was uncovered. Thus, p.Cys174Arg mutation was investigated as potentially responsible for the patient's inborn immunity error and aplastic anemia. Although STAT1 GOF is rare, aplastic anemia is a more common condition; therefore, we explored STAT1 functional role in the pathobiology of BM failure. Interestingly, in a cohort of six patients with idiopathic aplastic anemia, enhanced phospho-STAT1 levels were observed on BM immunostaining. Next, the most remarkable features associated with STAT1 signaling dysregulation were examined: in both pure red cell aplasia and aplastic anemia, CD8
+ T cell genetic variants and mutations display enhanced signaling activities related to the JAK-STAT pathway. Inborn errors of immunity may represent a paradigmatic condition to unravel crucial pathobiological mechanisms shared by common pathological conditions. Findings from our case-based approach and the phenotype correspondence to idiopathic aplastic anemia cases prompt further statistically powered prospective studies aiming to elucidate the exact role and theragnostic window for JAK/STAT targeting in this clinical context. Nonetheless, we demonstrate how a comprehensive study of patients with primary immunodeficiencies can lead to pathophysiologic insights and potential therapeutic approaches within a broader spectrum of aplastic anemia cases., (© 2023. The Author(s).)- Published
- 2023
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39. Immune disturbance leads to pulmonary embolism in COVID-19 more than classical risk factors: a clinical and histological study.
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Cicco S, Vacca A, Albanese F, Susca N, Desantis V, Magistro A, Cazzato G, Cicco G, Sablone S, Cariddi C, Marozzi MS, Catena C, Brosolo G, Marcante S, Ingravallo G, Dalfino L, Lauletta G, Pappagallo F, Solimando AG, Grasso S, Maiorano E, Introna F, Sechi LA, and Ria R
- Subjects
- Male, Female, Humans, Arteries, Oxygen, Research Design, Retrospective Studies, COVID-19 complications, Pulmonary Embolism epidemiology, Pulmonary Embolism etiology
- Abstract
COVID-19 induces endotheliitis and one of the main complications is enhanced coagulation. The incidence of pulmonary embolism (PE) in COVID-19 (CPE) has increased and clinical features for a rigorous analysis still need to be determined. Thus, we evaluated the clinical characteristics in CPE and the immune infiltration that occurred. Between January 1 and December 31, 2021, 38 patients were affected by CPE (9 ICU, 19 males/19 females, 70.18 ± 11.24 years) out of 459 COVID-19 cases. Controls were subjects who were evaluated for PE between January 1 2015, and December 31, 2019 (92 patients, 9 ICU, 48 males/45 females, 69.55 ± 16.59 years). All patients underwent complete physical examination, pulmonary computed tomography, laboratory tests, D-dimer, and blood gas analysis. There were no differences in laboratory tests or D-dimer. In patients with CPE, pO2, alveolar-arterial oxygen difference (A-aDO2), oxygen saturation %, and the ratio between arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2), P/F, were significantly increased. There were no differences in PaCO2. Platelet count was inversely correlated to P/F (r = - 0.389, p = 0.02) but directly to A-aDO2 (r = 0.699, p = 0.001) only in patients with CPE. Histology of lung biopsies (7 CPE/7 controls) of patients with CPE showed an increase in CD15
+ cells, HMGB1, and extracellular MPO as a marker of NETosis, while no significant differences were found in CD3+ , CD4+ , CD8+ , and intracellular MPO. Overall, data suggest that CPE has a different clinical setting. Reduced oxygen content and saturation described in Patients with CPE should not be considered a trustworthy sign of disease. Increased A-aDO2 may indicate that CPE involves the smallest vessels as compared to classical PE. The significant difference in NETosis may suggest the mechanism related to thrombi formation., (© 2023. The Author(s).)- Published
- 2023
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40. Breaking through Multiple Myeloma: A Paradigm for a Comprehensive Tumor Ecosystem Targeting.
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Solimando AG, Krebs M, Desantis V, Marziliano D, Caradonna IC, Morizio A, Argentiero A, Shahini E, and Bittrich M
- Abstract
Multiple myeloma (MM) is a cancerous condition characterized by the proliferation of plasma cells within the hematopoietic marrow, resulting in multiple osteolytic lesions. MM patients typically experience bone pain, kidney damage, fatigue due to anemia, and infections. Historically, MM was an incurable disease with a life expectancy of around three years after diagnosis. However, over the past two decades, the development of novel therapeutics has significantly improved patient outcomes, including response to treatment, remission duration, quality of life, and overall survival. These advancements include thalidomide and its derivatives, lenalidomide and pomalidomide, which exhibit diverse mechanisms of action against the plasma cell clone. Additionally, proteasome inhibitors such as bortezomib, ixazomib, and carfilzomib disrupt protein degradation, proving specifically toxic to cancerous plasma cells. Recent advancements also involve monoclonal antibodies targeting surface antigens, such as elotuzumab (anti-CS1) and daratumumab (anti-CD38), bispecific t-cell engagers such as teclistamab (anti-BCMA/CD3) and Chimeric antigen receptor T (CAR-T)-based strategies, with a growing focus on drugs that exhibit increasingly targeted action against neoplastic plasma cells and relevant effects on the tumor microenvironment.
- Published
- 2023
- Full Text
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41. The Effect of Diabetes and Hyperglycemia on Horizontal Guided Bone Regeneration: A Clinical Prospective Analysis.
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De Angelis P, Rella E, Manicone PF, De Rosa G, Gallottini S, Liguori MG, Papi P, Desantis V, Passarelli PC, and D'Addona A
- Abstract
Guided bone regeneration (GBR) is a reconstructive procedure for treating atrophic alveolar ridges. This study aims to assess the correlation between different glycemic control levels and clinical findings in patients undergoing horizontal GBR before implant placement. The study population consisted of all patients requiring horizontal GBR. Patients were divided into three groups based on HbA1c levels: non-diabetic normoglycemic patients (HbA1c < 5.7%), non-diabetic hyperglycaemic patients (HbA1c < 6.5%), and patients with controlled diabetes (HbA1c < 7%). The primary outcomes were the horizontal (mm) and vertical (mm) dimensional changes of the alveolar ridge 6 months after the procedure. The study sample consisted of 54 patients. Sixty-eight implants (95.8%) were classified as "successful," meaning the possibility of inserting a standard-sized implant following the GBR (diameter ≥ 4 mm). There was a statistically significant difference between the three groups in terms of horizontal gain at 6 months: in particular, there was a statistically significant difference between group 1 and group 2 ( p = 0.026) and between group 1 and group 3 ( p = 0.030). The present investigation showed that patients with HbA1c levels below 7% could undergo GBR and obtain a statistically significant horizontal bone gain.
- Published
- 2023
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42. Targeting the immune microenvironment in Waldenström macroglobulinemia via halting the CD40/CD40-ligand axis.
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Sacco A, Desantis V, Celay J, Giustini V, Rigali F, Savino FD, Cea M, Soncini D, Cagnetta A, Solimando AG, D'Aliberti D, Spinelli S, Ramazzotti D, Almici C, Todoerti K, Neri A, Anastasia A, Tucci A, Motta M, Chiarini M, Kawano Y, Martinez-Climent JA, Piazza R, and Roccaro AM
- Subjects
- Humans, Animals, Mice, CD40 Ligand genetics, Phosphatidylinositol 3-Kinases, Ligands, Signal Transduction, Tumor Microenvironment, Waldenstrom Macroglobulinemia pathology, Lymphoma, B-Cell complications
- Abstract
Recent investigations have improved our understanding of the molecular aberrations supporting Waldenström macroglobulinemia (WM) biology; however, whether the immune microenvironment contributes to WM pathogenesis remains unanswered. First, we showed how a transgenic murine model of human-like lymphoplasmacytic lymphoma/WM exhibits an increased number of regulatory T cells (Tregs) relative to control mice. These findings were translated into the WM clinical setting, in which the transcriptomic profiling of Tregs derived from patients with WM unveiled a peculiar WM-devoted messenger RNA signature, with significant enrichment for genes related to nuclear factor κB-mediated tumor necrosis factor α signaling, MAPK, and PI3K/AKT, which was paralleled by a different Treg functional phenotype. We demonstrated significantly higher Treg induction, expansion, and proliferation triggered by WM cells, compared with their normal cellular counterpart; with a more profound effect within the context of CXCR4C1013G-mutated WM cells. By investigating the B-cell-to-T-cell cross talk at single-cell level, we identified the CD40/CD40-ligand as a potentially relevant axis that supports WM cell-Tregs interaction. Our findings demonstrate the existence of a Treg-mediated immunosuppressive phenotype in WM, which can be therapeutically reversed by blocking the CD40L/CD40 axis to inhibit WM cell growth., (© 2023 by The American Society of Hematology.)
- Published
- 2023
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43. Uptake-Dependent and -Independent Effects of Fibroblasts-Derived Extracellular Vesicles on Bone Marrow Endothelial Cells from Patients with Multiple Myeloma: Therapeutic and Clinical Implications.
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Lamanuzzi A, Saltarella I, Reale A, Melaccio A, Solimando AG, Altamura C, Tamma G, Storlazzi CT, Tolomeo D, Desantis V, Mariggiò MA, Desaphy JF, Spencer A, Vacca A, Apollonio B, and Frassanito MA
- Abstract
Extracellular vesicles (EVs) have emerged as important players in cell-to-cell communication within the bone marrow (BM) of multiple myeloma (MM) patients, where they mediate several tumor-associated processes. Here, we investigate the contribution of fibroblasts-derived EVs (FBEVs) in supporting BM angiogenesis. We demonstrate that FBEVs' cargo contains several angiogenic cytokines (i.e., VEGF, HGF, and ANG-1) that promote an early over-angiogenic effect independent from EVs uptake. Interestingly, co-culture of endothelial cells from MM patients (MMECs) with FBEVs for 1 or 6 h activates the VEGF/VEGFR2, HGF/HGFR, and ANG-1/Tie2 axis, as well as the mTORC2 and Wnt/β-catenin pathways, suggesting that the early over-angiogenic effect is a cytokine-mediated process. FBEVs internalization occurs after longer exposure of MMECs to FBEVs (24 h) and induces a late over-angiogenic effect by increasing MMECs migration, chemotaxis, metalloproteases release, and capillarogenesis. FBEVs uptake activates mTORC1, MAPK, SRC, and STAT pathways that promote the release of pro-angiogenic cytokines, further supporting the pro-angiogenic milieu. Overall, our results demonstrate that FBEVs foster MM angiogenesis through dual time-related uptake-independent and uptake-dependent mechanisms that activate different intracellular pathways and transcriptional programs, providing the rationale for designing novel anti-angiogenic strategies.
- Published
- 2023
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44. microRNAs as Biomarkers of Endothelial Dysfunction and Therapeutic Target in the Pathogenesis of Atrial Fibrillation.
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Desantis V, Potenza MA, Sgarra L, Nacci C, Scaringella A, Cicco S, Solimando AG, Vacca A, and Montagnani M
- Subjects
- Humans, Heart Atria metabolism, Biomarkers metabolism, Fibrosis, MicroRNAs metabolism, Atrial Fibrillation genetics, Atrial Fibrillation complications, Vascular Diseases complications, Atrial Remodeling
- Abstract
The pathophysiology of atrial fibrillation (AF) may involve atrial fibrosis/remodeling and dysfunctional endothelial activities. Despite the currently available treatment approaches, the progression of AF, its recurrence rate, and the high mortality risk of related complications underlay the need for more advanced prognostic and therapeutic strategies. There is increasing attention on the molecular mechanisms controlling AF onset and progression points to the complex cell to cell interplay that triggers fibroblasts, immune cells and myofibroblasts, enhancing atrial fibrosis. In this scenario, endothelial cell dysfunction (ED) might play an unexpected but significant role. microRNAs (miRNAs) regulate gene expression at the post-transcriptional level. In the cardiovascular compartment, both free circulating and exosomal miRNAs entail the control of plaque formation, lipid metabolism, inflammation and angiogenesis, cardiomyocyte growth and contractility, and even the maintenance of cardiac rhythm. Abnormal miRNAs levels may indicate the activation state of circulating cells, and thus represent a specific read-out of cardiac tissue changes. Although several unresolved questions still limit their clinical use, the ease of accessibility in biofluids and their prognostic and diagnostic properties make them novel and attractive biomarker candidates in AF. This article summarizes the most recent features of AF associated with miRNAs and relates them to potentially underlying mechanisms.
- Published
- 2023
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45. Visualizing the Interactions Shaping the Imaging of the Microenvironment in Human Cancers.
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Solimando AG, Desantis V, and Da Vià MC
- Subjects
- Animals, High-Throughput Nucleotide Sequencing methods, Humans, Mice, RNA, Messenger, Transcriptome, Tumor Microenvironment, Gene Expression Profiling methods, Neoplasms genetics
- Abstract
The Visium Spatial Gene Expression Solution (Visium 10×) allows for the mRNA analysis using high throughput sequencing and maps a transcriptional expression pattern in tissue sections using high-resolution microscope imaging in ex-vivo human and mice samples. The workflow surveys spatial global gene expression in tissue sections, exploiting the whole transcriptome profiling and defining the set of transcripts via targeted gene panels. An automated cell type annotation allows a comparison with control tissue samples. This technique delineates cancerous or diseased tissue boundaries and details gene expression gradients in the tissue surrounding the tumor or pathologic nests. Remarkably, the Visium 10× allows for whole transcriptome and targeted analysis without the loss of spatial information. This approach provides gene expression data within the context of tissue architecture, tissue microenvironments, and cell groups. It can be used in association with therapy, anti-angiogenic therapy, and immunotherapy to improve treatment response., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2023
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46. Mast Cells and Interleukins.
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Solimando AG, Desantis V, and Ribatti D
- Subjects
- Cell Count, Cytokines, Biological Transport, Mast Cells, Interleukins
- Abstract
Mast cells play a critical role in inflammatory diseases and tumor growth. The versatility of mast cells is reflected in their ability to secrete a wide range of biologically active cytokines, including interleukins, chemokines, lipid mediators, proteases, and biogenic amines. The aim of this review article is to analyze the complex involvement of mast cells in the secretion of interleukins and the role of interleukins in the regulation of biological activities of mast cells.
- Published
- 2022
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47. Implant Placement with Simultaneous Guided Bone Regeneration Using Advanced Platelet-Rich Fibrin and a Deproteinized Bovine Bone Mineral: A 2-Year Retrospective and Comparative Study.
- Author
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De Angelis P, Manicone PF, De Angelis S, Passarelli PC, Desantis V, Romeo A, Liguori MG, and D'Addona A
- Subjects
- Humans, Cattle, Animals, Guided Tissue Regeneration, Periodontal methods, Dental Implantation, Endosseous methods, Retrospective Studies, Bone Regeneration, Minerals therapeutic use, Platelet-Rich Fibrin, Dental Implants, Biological Products
- Abstract
A lack of bone volume may compromise a correct three-dimensional implant placement. This study was designed to evaluate the clinical and radiographic outcomes of simultaneous horizontal guided bone regeneration (GBR) performed using autogenous bone or blood-derived products mixed with a bone xenograft. The study population consisted of patients operated on using one of two clinical protocols for GBR: group A, which used autogenous bone mixed with a bone xenograft, and group B, which used advanced platelet-rich fibrin (A-PRF) mixed with a bone xenograft. The primary outcome was the clinical gain in the peri-implant defect. The secondary outcomes included an analysis of the postoperative healing, periodontal parameters, marginal bone loss, and occurrence of adverse events. All of the surgeries were carried out successfully. One patient in each group experienced a case of early implant loss, and three patients (one in group A and two in group B) presented biologic complications. The mean peri-implant vertical defect heights at baseline in group A and group B were 3.6 ± 0.9 mm and 4 ± 1.5 mm, respectively (P = .382). No statistically significant differences in the mean residual defect heights (P = .521) or in the postoperative wound healing (P = .611) were observed. Stable peri-implant marginal bone levels were recorded after loading in both groups. The use of A-PRF combined with a particulate bone xenograft and covered with a fixed collagen membrane may provide clinical results similar to those obtained via autogenous bone mixed with bone xenograft.
- Published
- 2022
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48. Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance.
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Melaccio A, Reale A, Saltarella I, Desantis V, Lamanuzzi A, Cicco S, Frassanito MA, Vacca A, and Ria R
- Abstract
Multiple myeloma (MM) is the second most common hematological malignancy, and despite the introduction of innovative therapies, remains an incurable disease. Identifying early and minimally or non-invasive biomarkers for predicting clinical outcomes and therapeutic responses is an active field of investigation. Malignant plasma cells (PCs) reside in the bone marrow (BM) microenvironment (BMME) which comprises cells (e.g., tumour, immune, stromal cells), components of the extracellular matrix (ECM) and vesicular and non-vesicular (soluble) molecules, all factors that support PCs' survival and proliferation. The interaction between PCs and BM stromal cells (BMSCs), a hallmark of MM progression, is based not only on intercellular interactions but also on autocrine and paracrine circuits mediated by soluble or vesicular components. In fact, PCs and BMSCs secrete various cytokines, including angiogenic cytokines, essential for the formation of specialized niches called "osteoblastic and vascular niches", thus supporting neovascularization and bone disease, vital processes that modulate the pathophysiological PCs-BMME interactions, and ultimately promoting disease progression. Here, we aim to discuss the roles of cytokines and growth factors in pathogenetic pathways in MM and as prognostic and predictive biomarkers. We also discuss the potential of targeted drugs that simultaneously block PCs' proliferation and survival, PCs-BMSCs interactions and BMSCs activity, which may represent the future goal of MM therapy.
- Published
- 2022
- Full Text
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49. Cardiovascular Risk in Patients With Takayasu Arteritis Directly Correlates With Diastolic Dysfunction and Inflammatory Cell Infiltration in the Vessel Wall: A Clinical, ex vivo and in vitro Analysis.
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Cicco S, Desantis V, Vacca A, Cazzato G, Solimando AG, Cirulli A, Noviello S, Susca C, Prete M, Brosolo G, Catena C, Lamanuzzi A, Saltarella I, Frassanito MA, Cimmino A, Ingravallo G, Resta L, Ria R, and Montagnani M
- Abstract
Background: Takayasu Arteritis (TAK) increases vascular stiffness and arterial resistance. Atherosclerosis leads to similar changes. We investigated possible differences in cardiovascular remodeling between these diseases and whether the differences are correlated with immune cell expression., Methods: Patients with active TAK arteritis were compared with age- and sex-matched atherosclerotic patients (Controls). In a subpopulation of TAK patients, Treg/Th17 cells were measured before (T0) and after 18 months (T18) of infliximab treatment. Echocardiogram, supraaortic Doppler ultrasound, and lymphocytogram were performed in all patients. Histological and immunohistochemical changes of the vessel wall were evaluated as well., Results: TAK patients have increased aortic valve dysfunction and diastolic dysfunction. The degree of dysfunction appears associated with uric acid levels. A significant increase in aortic stiffness was also observed and associated with levels of peripheral T lymphocytes. CD3
+ CD4+ cell infiltrates were detected in the vessel wall samples of TAK patients, whose mean percentage of Tregs was lower than Controls at T0, but increased significantly at T18. Opposite behavior was observed for Th17 cells. Finally, TAK patients were found to have an increased risk of atherosclerotic cardiovascular disease (ASCVD)., Conclusion: Our data suggest that different pathogenic mechanisms underlie vessel damage, including atherosclerosis, in TAK patients compared with Controls. The increased risk of ASCVD in TAK patients correlates directly with the degree of inflammatory cell infiltration in the vessel wall. Infliximab restores the normal frequency of Tregs/Th17 in TAK patients and allows a possible reduction of steroids and immunosuppressants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cicco, Desantis, Vacca, Cazzato, Solimando, Cirulli, Noviello, Susca, Prete, Brosolo, Catena, Lamanuzzi, Saltarella, Frassanito, Cimmino, Ingravallo, Resta, Ria and Montagnani.)- Published
- 2022
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50. The Leading Role of the Immune Microenvironment in Multiple Myeloma: A New Target with a Great Prognostic and Clinical Value.
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Desantis V, Savino FD, Scaringella A, Potenza MA, Nacci C, Frassanito MA, Vacca A, and Montagnani M
- Abstract
Multiple myeloma (MM) is a plasma cell (PC) malignancy whose development flourishes in the bone marrow microenvironment (BMME). The BMME components' immunoediting may foster MM progression by favoring initial immunotolerance and subsequent tumor cell escape from immune surveillance. In this dynamic process, immune effector cells are silenced and become progressively anergic, thus contributing to explaining the mechanisms of drug resistance in unresponsive and relapsed MM patients. Besides traditional treatments, several new strategies seek to re-establish the immunological balance in the BMME, especially in already-treated MM patients, by targeting key components of the immunoediting process. Immune checkpoints, such as CXCR4, T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT), PD-1, and CTLA-4, have been identified as common immunotolerance steps for immunotherapy. B-cell maturation antigen (BCMA), expressed on MMPCs, is a target for CAR-T cell therapy, antibody-(Ab) drug conjugates (ADCs), and bispecific mAbs. Approved anti-CD38 (daratumumab, isatuximab), anti-VLA4 (natalizumab), and anti-SLAMF7 (elotuzumab) mAbs interfere with immunoediting pathways. New experimental drugs currently being evaluated (CD137 blockers, MSC-derived microvesicle blockers, CSF-1/CSF-1R system blockers, and Th17/IL-17/IL-17R blockers) or already approved (denosumab and bisphosphonates) may help slow down immune escape and disease progression. Thus, the identification of deregulated mechanisms may identify novel immunotherapeutic approaches to improve MM patients' outcomes.
- Published
- 2022
- Full Text
- View/download PDF
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