au:"Longhitano, Lucia" (12)
Osteosclerose (1)
Focus on Osteosclerotic Progression in Primary Myelofibrosis.
Spampinato, Mariarita; Giallongo, Cesarina; Romano, Alessandra; Longhitano, Lucia; La Spina, Enrico; Avola, Roberto; Scandura, Grazia; Dulcamare, Ilaria; Bramanti, Vincenzo; Di Rosa, Michelino; Vicario, Nunzio; Parenti, Rosalba; Li Volti, Giovanni; Tibullo, Daniele; Palumbo, Giuseppe A.
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hematopoietic stem-cell-derived clonal proliferation, leading to bone marrow (BM) fibrosis. Hematopoiesis alterations are closely associated with modifications of the BM microenvironment, characterized by defective interactions between vascular and endosteal niches. As such, neoangiogenesis, megakaryocytes hyperplasia and extensive bone marrow fibrosis, followed by osteosclerosis and bone damage, are the most relevant consequences of PMF. Moreover, bone tissue deposition, together with progressive fibrosis, represents crucial mechanisms of disabilities in patients. Although the underlying mechanisms of bone damage observed in PMF are still unclear, the involvement of cytokines, growth factors and bone marrow microenvironment resident cells have been linked to disease progression. Herein, we focused on the role of megakaryocytes and their alterations, associated with cytokines and chemokines release, in modulating functions of most of the bone marrow cell populations and in creating a complex network where impaired signaling strongly contributes to progression and disabilities.
Progressão da Doença , Osteosclerose/parasitologia , Mielofibrose Primária/patologia , Animais , Medula Óssea , Humanos , Monócitos/patologia , Transdução de Sinais
The Role of Inflammation and Inflammasome in Myeloproliferative Disease.
Longhitano, Lucia; Li Volti, Giovanni; Giallongo, Cesarina; Spampinato, Mariarita; Barbagallo, Ignazio; Di Rosa, Michelino; Romano, Alessandra; Avola, Roberto; Tibullo, Daniele; Palumbo, Giuseppe Alberto.
Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are rare hematological conditions known as myeloproliferative neoplasms (MPNs). They are characterized for being BCR-ABL negative malignancies and affected patients often present with symptoms which can significantly impact their quality of life. MPNs are characterized by a clonal proliferation of an abnormal hematopoietic stem/progenitor cell. In MPNs; cells of all myeloid lineages; including those involved in the immune and inflammatory response; may belong to the malignant clone thus leading to an altered immune response and an overexpression of cytokines and inflammatory receptors; further worsening chronic inflammation. Many of these cytokines; in particular, IL-1ß and IL-18; are released in active form by activating the inflammasome complexes which in turn mediate the inflammatory process. Despite this; little is known about the functional effects of stem cell-driven inflammasome signaling in MPN pathogenesis. In this review we focused on the role of inflammatory pathway and inflammasome in MPN diseases. A better understanding of the inflammatory-state-driving MPNs and of the role of the inflammasome may provide new insights on possible therapeutic strategies.
Proteasome Inhibitors as a Possible Therapy for SARS-CoV-2.
Longhitano, Lucia; Tibullo, Daniele; Giallongo, Cesarina; Lazzarino, Giacomo; Tartaglia, Nicola; Galimberti, Sara; Li Volti, Giovanni; Palumbo, Giuseppe Alberto; Liso, Arcangelo.
The COVID-19 global pandemic is caused by SARS-CoV-2, and represents an urgent medical and social issue. Unfortunately, there is still not a single proven effective drug available, and therefore, current therapeutic guidelines recommend supportive care including oxygen administration and treatment with antibiotics. Recently, patients have been also treated with off-label therapies which comprise antiretrovirals, anti-inflammatory compounds, antiparasitic agents and plasma from convalescent patients, all with controversial results. The ubiquitin-proteasome system (UPS) is important for the maintenance of cellular homeostasis, and plays a pivotal role in viral replication processes. In this review, we discuss several aspects of the UPS and the effects of its inhibition with particular regard to the life cycle of the coronaviruses (CoVs). In fact, proteasome inhibition by various chemical compounds, such as MG132, epoxomycin and bortezomib, may reduce the virus entry into the eucariotic cell, the synthesis of RNA, and the subsequent protein expression necessary for CoVs. Importantly, since UPS inhibitors reduce the cytokine storm associated with various inflammatory conditions, it is reasonable to assume that they might be repurposed for SARS-CoV-2, thus providing an additional tool to counteract both virus replication as well as its most deleterious consequences triggered by abnormal immunological response.
Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Inibidores de Proteassoma/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/epidemiologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Oligopeptídeos/farmacologia , Oligopeptídeos/uso terapêutico , Pandemias , Pneumonia Viral/epidemiologia , Inibidores de Proteassoma/farmacologia , SARS-CoV-2
Effects of micronised microencapsulated ferric pyrophosphate supplementation in patients with advanced cancer and iron deficiency: a single-centre cohort pilot study.
Pappalardo, Alessandro; Currenti, Walter; Ponzio, Rossella; Mellini, Giulio; Nicolosi, Daniela; Longhitano, Lucia; Tibullo, Daniele; Castorina, Sergio; Palumbo, Giuseppe.
BACKGROUND: Iron deficiency is the most common nutritional deficiency in advanced cancer patients and causes anaemia. Iron deficiency anaemia treatment (i.e. intravenous or oral iron administration) has been demonstrated to be effective but is often associated with adverse reactions. Micronised microencapsulated ferric pyrophosphate (MMFP) is a recently developed formulation characterised by a higher intestinal bioavailability due to the small particle size distribution at nanometer level. The aim of this study was to evaluate the efficacy of an oral administration of 30 mg of MMFP associated with 80 mg of ascorbic acid in advanced cancer patients with hyposideraemia. MATERIALS AND METHODS: This was an observational prospective cohort study (10 months) conducted on 42 adult patients with advanced cancer and serum iron levels lower than 60 µg/dL. All patients received one capsule/day for 30 days of a supplement containing 30 mg of MMFP and 80 mg of ascorbic acid. At enrolment (T0) and at 30 days (T1) patients were subjected to blood sampling for evaluation of serum iron, ferritinaemia and blood count. In addition, any undesirable effects reported by patients were evaluated. RESULTS: MMFP treatment increased sideraemia from 36.1±8.37 µg/dL to 73.22±28.60 µg/dL, haemoglobin from 10.43±1.09 g/dL to 11.52±1.90 g/dL, and ferritinaemia from 42.10±16.90 ng/mL to 123.33±55.79 ng/mL. No adverse effects were noted from the use of MMFP supplementation. DISCUSSION: The supplementation of 30 mg/d of MMFP in combination with 80 mg/d of ascorbic acid in advanced cancer patients with hyposideraemia led to a significant increase in sideraemia and ferritinaemia. Moreover, in some of the patients whose serum iron level did not increase, an increase in haemoglobin was observed.
Anemia Ferropriva , Difosfatos/administração & dosagem , Ferro/administração & dosagem , Neoplasias , Administração Intravenosa , Administração Oral , Idoso , Anemia Ferropriva/sangue , Anemia Ferropriva/tratamento farmacológico , Feminino , Humanos , Ferro/sangue , Ferro/deficiência , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Projetos Piloto , Estudos Prospectivos
Salerno, Monica; Villano, Ines; Nicolosi, Daniela; Longhitano, Lucia; Loreto, Carla; Lovino, Annarita; Sessa, Francesco; Polito, Anna Nunzia; Monda, Vincenzo; Chieffi, Sergio; Messina, Antonietta; Monda, Marcellino; Zammit, Christian; Tafuri, Domenico; Messina, Giovanni; Carotenuto, Marco.
Sistema Nervoso Central/efeitos dos fármacos , Modafinila/farmacologia , Orexinas/metabolismo , Vigília/efeitos dos fármacos , Animais , Atenção/efeitos dos fármacos , Atenção/fisiologia , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/fisiologia , Cognição/efeitos dos fármacos , Cognição/fisiologia , Humanos , Modafinila/metabolismo , Modafinila/farmacocinética , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/fisiologia , Vigília/fisiologia , Promotores da Vigília/metabolismo , Promotores da Vigília/farmacocinética , Promotores da Vigília/farmacologia
Lorusso, Letizia; Salerno, Monica; Sessa, Francesco; Nicolosi, Daniela; Longhitano, Lucia; Loreto, Carla; Carotenuto, Marco; Messina, Antonietta; Monda, Vincenzo; Villano, Ines; Cibelli, Giuseppe; Valenzano, Anna; Monda, Marcellino; Murabito, Paolo; Mollica, Maria Pina; Messina, Giovanni; Viggiano, Andrea.
Longhitano, Lucia; Castracani, Carlo Castruccio; Tibullo, Daniele; Avola, Roberto; Viola, Maria; Russo, Giuliano; Prezzavento, Orazio; Marrazzo, Agostino; Amata, Emanuele; Reibaldi, Michele; Longo, Antonio; Russo, Andrea; Parrinello, Nunziatina Laura; Volti, Giovanni Li.
Uveal melanoma is the most common primary intraocular tumor in adults, with about 1200-1500 new cases occurring per year in the United States. Metastasis is a frequent occurrence in uveal melanoma, and outcomes are poor once distant spread occurs and no clinically significant chemotherapeutic protocol is so far available. The aim of the present study was to test the effect of various σ1 and σ2 receptor ligands as a possible pharmacological strategy for this rare tumor. Human uveal melanoma cells (92.1) were treated with various concentrations of different σ2 ligands (haloperidol and haloperidol metabolite II) and σ1 ligand ((+)-pentazocine) at various concentrations (1, 10 and 25 µM) and time points (0, 4 h, 8 h, 24 h and 48 h). Cell proliferation and migration were evaluated respectively by continuous cell monitoring by xCELLigence analysis, clonogenic assay and wound healing. Apoptosis and autophagy were also measured by cytofluorimetric and microscopy analysis. Our results showed that σ2 receptor ligands significantly reduced cell proliferation whereas (+)-pentazocine exhibited opposite results. All tested ligands showed significant decrease in cell migration. Interestingly, both σ1 and σ2 receptor ligands showed significant increase of autophagy and apoptosis at all concentrations. Taken all together these results suggest that sigma receptors mediates opposite biological effects but they also share common pharmacological effect on apoptosis and autophagy in uveal melanoma. In conclusion, these data provide the first evidence that sigma receptors may represent a "druggable" target to develop new chemotherapic agent for uveal melanoma.
au:"Longhitano, Lucia"