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7. Homotypic and Heterotypic Activation of the Notch Pathway in Multiple Myeloma–Enhanced Angiogenesis: A Novel Therapeutic Target?

Author

Saltarella, Ilaria, Frassanito, Maria Antonia, Lamanuzzi, Aurelia, Brevi, Arianna, Leone, Patrizia, Desantis, Vanessa, Di Marzo, Lucia, Bellone, Matteo, Derudas, Daniele, Ribatti, Domenico, Chiaramonte, Raffaella, Palano, Maria Teresa, Neri, Antonino, Mariggiò, Maria Addolorata, Fumarulo, Ruggiero, Dammacco, Franco, Racanelli, Vito, Vacca, Angelo, and Ria, Roberto

Published
2019
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10. Prognostic or predictive value of circulating cytokines and angiogenic factors for initial treatment of multiple myeloma in the GIMEMA MM0305 randomized controlled trial

Author

Saltarella, Ilaria, Morabito, Fortunato, Giuliani, Nicola, Terragna, Carolina, Omedè, Paola, Palumbo, Antonio, Bringhen, Sara, De Paoli, Lorenzo, Martino, Enrica, Larocca, Alessandra, Offidani, Massimo, Patriarca, Francesca, Nozzoli, Chiara, Guglielmelli, Tommasina, Benevolo, Giulia, Callea, Vincenzo, Baldini, Luca, Grasso, Mariella, Leonardi, Giovanna, Rizzo, Manuela, Falcone, Antonietta Pia, Gottardi, Daniela, Montefusco, Vittorio, Musto, Pellegrino, Petrucci, Maria Teresa, Dammacco, Franco, Boccadoro, Mario, Vacca, Angelo, and Ria, Roberto

Published
2019
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18. Giant Cell Arteritis: The Experience of Two Collaborative Referral Centers and an Overview of Disease Pathogenesis and Therapeutic Advancements

Author

Dammacco, Rosanna, Alessio, Giovanni, Giancipoli, Ermete, Leone, Patrizia, Cirulli, Anna, Resta, Leonardo, Vacca, Angelo, and Dammacco, Franco

Subjects
tocilizumab, glucocorticoids, pathogenetic advances, giant cell arteritis, diagnostic imaging, Clinical Ophthalmology, ocular manifestations, Original Research
Abstract

Rosanna Dammacco,1 Giovanni Alessio,1 Ermete Giancipoli,2 Patrizia Leone,3 Anna Cirulli,3 Leonardo Resta,4 Angelo Vacca,3 Franco Dammacco3 1Department of Ophthalmology and Neuroscience, University of Bari “Aldo Moro”, Medical School, Bari, Italy; 2Department of Biomedical Sciences, Ophthalmology Unit, University of Sassari, Sassari, Italy; 3Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, Medical School, Bari, Italy; 4Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Medical School, Bari, ItalyCorrespondence: Franco DammaccoDepartment of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, Medical School, Polyclinic, Piazza Giulio Cesare, 11, Bari 70124, ItalyTel +39 080 5478 863Fax +39 080 5478 820Email francesco.dammacco@uniba.itPurpose: Giant cell arteritis (GCA), a chronic vasculitis of the large and medium-sized arteries, affects people > 50 years of age. This study assessed the prevalence of visual manifestations and other clinical features at presentation in an Italian cohort of GCA patients. Recent advances in the pathophysiology, diagnosis, and therapy of GCA are also reviewed.Methods: This retrospective, single-center study conducted by the ophthalmology and internal medicine clinics of one university recruited 56 patients from 2005 to 2016 and followed them for 11– 54 months.Results: Ocular involvement was diagnosed in 19 patients (33.9%), with permanent vision loss in 19.6% (7.1% of the cohort with bilateral vision loss). Arteritic anterior and posterior ischemic optic neuropathy were diagnosed in 11 patients (57.9%) and 1 patient (5.3%), respectively, cotton wool spots in 3 patients (15.8%), central retinal artery occlusion in 2 patients (10.5%), and anterior segment ischemia and multifocal choroidal ischemia in 1 patient each (5.3%). Polymyalgia rheumatica was associated with GCA in 44.6% of the patients. The most common extra-ocular manifestation was constitutional symptoms (82.1% of the patients). Large-vessel involvement, including of the ascending aorta, aortic arch, and left axillary artery, was diagnosed by magnetic resonance or computed tomography (CT) angiography and 18FDG positron emission/CT. Glucocorticoids (GCs) remain the standard-of-care worldwide, but methotrexate, provided as a steroid-sparing drug in 41% of the patients, resulted in earlier tapering, a lower cumulative dose of GCs, and a lower rate of relapse. Among the combinations of GCs and immunosuppressive drugs proposed to treat GCA, only tocilizumab has effectively induced and maintained disease remission.Conclusion: According to our data and literature reports: a) GCA is a systemic disease; b) its diagnosis is expedited by the adjunct use of imaging techniques; c) insights into the pathogenesis of GCA may allow an improved, differentiated therapeutic approach.Keywords: giant cell arteritis, ocular manifestations, diagnostic imaging, glucocorticoids, pathogenetic advances, tocilizumab

Published
2020

31. Homotypic and Heterotypic Activation of the Notch Pathway in Multiple Myeloma–Enhanced Angiogenesis: A Novel Therapeutic Target?1

Author

Saltarella, Ilaria, Frassanito, Maria Antonia, Lamanuzzi, Aurelia, Brevi, Arianna, Leone, Patrizia, Desantis, Vanessa, Di Marzo, Lucia, Bellone, Matteo, Derudas, Daniele, Ribatti, Domenico, Chiaramonte, Raffaella, Palano, Maria Teresa, Neri, Antonino, Mariggiò, Maria Addolorata, Fumarulo, Ruggiero, Dammacco, Franco, Racanelli, Vito, Vacca, Angelo, and Ria, Roberto

Subjects
Vascular Endothelial Growth Factor A, Original article, Neovascularization, Pathologic, Receptors, Notch, Immunohistochemistry, Monoclonal Gammopathy of Undetermined Significance, Vascular Endothelial Growth Factor Receptor-2, Xenograft Model Antitumor Assays, Disease Models, Animal, Mice, Cell Line, Tumor, Benzene Derivatives, Animals, Humans, RNA Interference, Sulfones, Propionates, RNA, Small Interfering, Multiple Myeloma, Signal Transduction
Abstract

Interactions of multiple myeloma (MM) cells with endothelial cells (ECs) enhance angiogenesis and MM progression. Here, we investigated the role of Notch signaling in the cross talk between ECs and MM cells enabling angiogenesis. MMECs showed higher expression of Jagged1/2 ligands, of activated Notch1/2 receptors, and of Hes1/Hey1 Notch target genes than ECs from monoclonal gammopathy of undetermined significance patients, suggesting that homotypic activation of Notch pathway occurs in MM. MM cells co-cultured with MMECs triggered Notch activation in these cells through a cell-to-cell contact-dependent way via Jagged1/2, resulting in Hes1/Hey1 overexpression. The angiogenic effect of Notch pathway was analyzed through Notch1/2·siRNAs and the γ-secretase inhibitor MK-0752 by in vitro (adhesion, migration, chemotaxis, angiogenesis) and in vivo (Vk12598/C57B/6 J mouse model) studies. Activated Notch1/2 pathway was associated with the overangiogenic MMEC phenotype: Notch1/2 knockdown or MK-0752 treatment reduced Hes1/Hey1 expression, impairing in vitro angiogenesis of both MMECs alone and co-cultured with MM cells. MM cells were unable to restore angiogenic abilities of treated MMECs, proving that MMEC angiogenic activities closely rely on Notch pathway. Furthermore, Notch1/2 knockdown affected VEGF/VEGFR2 axis, indicating that the Notch pathway interferes with VEGF-mediated control on angiogenesis. MK-0752 reduced secretion of proangiogenic/proinflammatory cytokines in conditioned media, thus inhibiting blood vessel formation in the CAM assay. In the Vk12598/C57B/6 J mouse, MK-0752 treatment restrained angiogenesis by reducing microvessel density. Overall, homotypic and heterotypic Jagged1/2-mediated Notch activation enhances MMECs angiogenesis. Notch axis inhibition blocked angiogenesis in vitro and in vivo, suggesting that the Notch pathway may represent a novel therapeutic target in MM.

Published
2018

40. Giant Cell Arteritis: The Experience of Two Collaborative Referral Centers and an Overview of Disease Pathogenesis and Therapeutic Advancements

Author

Dammacco,Rosanna, Alessio,Giovanni, Giancipoli,Ermete, Leone,Patrizia, Cirulli,Anna, Resta,Leonardo, Vacca,Angelo, Dammacco,Franco, Dammacco,Rosanna, Alessio,Giovanni, Giancipoli,Ermete, Leone,Patrizia, Cirulli,Anna, Resta,Leonardo, Vacca,Angelo, and Dammacco,Franco

Abstract

Rosanna Dammacco,1 Giovanni Alessio,1 Ermete Giancipoli,2 Patrizia Leone,3 Anna Cirulli,3 Leonardo Resta,4 Angelo Vacca,3 Franco Dammacco3 1Department of Ophthalmology and Neuroscience, University of Bari “Aldo Moro”, Medical School, Bari, Italy; 2Department of Biomedical Sciences, Ophthalmology Unit, University of Sassari, Sassari, Italy; 3Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, Medical School, Bari, Italy; 4Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Medical School, Bari, ItalyCorrespondence: Franco DammaccoDepartment of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, Medical School, Polyclinic, Piazza Giulio Cesare, 11, Bari 70124, ItalyTel +39 080 5478 863Fax +39 080 5478 820Email francesco.dammacco@uniba.itPurpose: Giant cell arteritis (GCA), a chronic vasculitis of the large and medium-sized arteries, affects people > 50 years of age. This study assessed the prevalence of visual manifestations and other clinical features at presentation in an Italian cohort of GCA patients. Recent advances in the pathophysiology, diagnosis, and therapy of GCA are also reviewed.Methods: This retrospective, single-center study conducted by the ophthalmology and internal medicine clinics of one university recruited 56 patients from 2005 to 2016 and followed them for 11– 54 months.Results: Ocular involvement was diagnosed in 19 patients (33.9%), with permanent vision loss in 19.6% (7.1% of the cohort with bilateral vision loss). Arteritic anterior and posterior ischemic optic neuropathy were diagnosed in 11 patients (57.9%) and 1 patient (5.3%), respectively, cotton wool spots in 3 patients (15.8%), central retinal artery occlusion in 2 patients (10.5%), and anterior segment ischemia and multifocal choroidal ischemia in 1 patient each (5.3%). Polymyalgia rheumatica was associate

Published
2020

41. Intermediate-dose melphalan improves survival of myeloma patients aged 50 to 70: results of a randomized controlled trial

Author

Palumbo, Antonio, Bringhen, Sara, Petrucci, Maria Teresa, Musto, Pellegrino, Rossini, Fausto, Nunzi, Martina, Lauta, Vito Michele, Bergonzi, Cesare, Barbui, Anna, Caravita, Tommaso, Capaldi, Antonio, Pregno, Patrizia, Guglielmelli, Tommasina, Grasso, Mariella, Callea, Vincenzo, Bertola, Alessandra, Cavallo, Federica, Falco, Patrizia, Rus, Cecilia, Massaia, Massimo, Mandelli, Franco, Carella, Angelo Michele, Pogliani, Enrico, Liberati, Anna Marina, Dammacco, Franco, Ciccone, Giovannino, and Boccadoro, Mario

Published
2004
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45. Additional file 1: of Prognostic or predictive value of circulating cytokines and angiogenic factors for initial treatment of multiple myeloma in the GIMEMA MM0305 randomized controlled trial

Author

Saltarella, Ilaria, Morabito, Fortunato, Giuliani, Nicola, Terragna, Carolina, Omedè, Paola, Palumbo, Antonio, Bringhen, Sara, Paoli, Lorenzo De, Martino, Enrica, Larocca, Alessandra, Offidani, Massimo, Patriarca, Francesca, Nozzoli, Chiara, Guglielmelli, Tommasina, Benevolo, Giulia, Callea, Vincenzo, Baldini, Luca, Grasso, Mariella, Leonardi, Giovanna, Rizzo, Manuela, Falcone, Antonietta, Gottardi, Daniela, Montefusco, Vittorio, Musto, Pellegrino, Petrucci, Maria, Dammacco, Franco, Boccadoro, Mario, Vacca, Angelo, and Ria, Roberto

Abstract

Table S1. CAF levels in serum and bone marrow plasma of MM patients. Table S2. Cutoff for serum levels of cytokines and angiogenic factors (CAFs). Table S3. PFS and OS correlation with CAF levels (PDF 460 kb)

Published
2019
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47. Early echocardiographic detection of left ventricular diastolic dysfunction in patients with systemic lupus erythematosus asymptomatic for cardiovascular disease

Author

Leone, Patrizia, primary, Cicco, Sebastiano, additional, Prete, Marcella, additional, Solimando, Antonio Giovanni, additional, Susca, Nicola, additional, Crudele, Lucilla, additional, Buonavoglia, Alessio, additional, Colonna, Paolo, additional, Dammacco, Franco, additional, Vacca, Angelo, additional, and Racanelli, Vito, additional

Published
2019
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48. Correction: Resveratrol Exerts Antiproliferative Activity and Induces Apoptosis in Waldenström Macroglobulinemia

Author

Roccaro, Aldo M., primary, Leleu, Xavier, additional, Sacco, Antonio, additional, Moreau, Anne-Sophie, additional, Hatjiharissi, Evdoxia, additional, Jia, Xiaoying, additional, Xu, Lian, additional, Ciccarelli, Bryan, additional, Patterson, Christopher J., additional, Ngo, Hai T., additional, Russo, Domenico, additional, Vacca, Angelo, additional, Dammacco, Franco, additional, Anderson, Kenneth C., additional, Ghobrial, Irene M., additional, and Treon, Steven P., additional

Published
2019
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