15 results on '"Rivella, Stefano"'
Search Results
2. Inclusion of a short hairpin RNA targeting BCL11A into a β-globin expressing vector allows concurrent synthesis of curative adult and fetal hemoglobin
- Author
-
Pires Lourenco, Silvia, primary, Jarocha, Danuta, additional, Ghiaccio, Valentina, additional, Guerra, Amaliris, additional, Abdulmalik, Osheiza, additional, La, Ping, additional, Zezulin, Alexandra, additional, Smith-Whitley, Kim, additional, Kwiatkowski, Janet L., additional, Guzikowski, Virginia, additional, Nakamura, Yukio, additional, Raabe, Tobias, additional, Breda, Laura, additional, and Rivella, Stefano, additional
- Published
- 2021
- Full Text
- View/download PDF
3. Recommendations regarding splenectomy in hereditary hemolytic anemias
- Author
-
Iolascon, Achille, Andolfo, Immacolata, Barcellini, Wilma, Corcione, Francesco, Garçon, Loïc, De Franceschi, Lucia, Pignata, Claudio, Graziadei, Giovanna, Pospisilova, Dagmar, Rees, David C., Montalembert, Mariane, Rivella, Stefano, Gambale, Antonella, Russo, Roberta, Ribeiro, Leticia, Vives-Corrons, Jules, Martinez, Patricia Aguilar, Kattamis, Antonis, Gulbis, Beatrice, Cappellini, Maria Domenica, Roberts, Irene, Tamary, Hannah, Cells, Working Study Group, EHA, Iron, Chair of Medical Genetics, Department of Molecular Medicine and Medical Biotechnologies, University Federico II, Naples, and CEINGE-Advanced Biotechnologies, Naples, Italy, Internal Medicine, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Dept. of Pediatrics, Palacky University Olomouc, Department of Paediatric Haematology, Kings College Hospital, Service de pédiatrie générale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Centre de Référence de la Drépanocytose-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), First Department of Paediatrics, Athens University, Thalassaemia Unit, 'Aghia Sofia' Children's Hospital, Pediatric Hematology Unit (Pediatric Hematology Unit), Schneider Children's Medical Center of Israel, Palacky University, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Centre de Référence de la Drépanocytose, Iolascon, Achille, Andolfo, Immacolata, Barcellini, Wilma, Corcione, Francesco, Garçon, Loïc, DE FRANCESCHI, Lucia, Pignata, Claudio, Graziadei, Giovanna, Pospisilova, Dagmar, Rees, David C, de Montalembert, Mariane, Rivella, Stefano, Gambale, Antonella, Russo, Roberta, Ribeiro, Leticia, Vives Corrons, Jule, Aguilar Martinez, Patricia, Kattamis, Antoni, Gulbis, Beatrice, Cappellini, MARIA DOMENICA, Roberts, Irene, and Tamary, Hannah
- Subjects
medicine.medical_specialty ,Pediatrics ,Anemia ,[SDV]Life Sciences [q-bio] ,medicine.medical_treatment ,Thalassemia ,Red Cells ,Splenectomy ,Guidelines as Topic ,Disease ,Antithrombotic Therapy ,Anemia, Hemolytic, Congenital ,Hereditary Hemolytic Anemia ,Hereditary spherocytosis ,Guideline Article ,03 medical and health sciences ,Therapeutic approach ,0302 clinical medicine ,Red Cell Membrane Disorder ,Internal medicine ,medicine ,Humans ,Infectious Disorder ,Hematology ,business.industry ,Thrombosis ,medicine.disease ,3. Good health ,Surgery ,Red Cell Enzyme Abnormalitie ,030220 oncology & carcinogenesis ,business ,Hématologie ,030215 immunology - Abstract
Hereditary hemolytic anemias are a group of disorders with a variety of causes, including red cell membrane defects, red blood cell enzyme disorders, congenital dyserythropoietic anemias, thalassemia syndromes and hemoglobinopathies. As damaged red blood cells passing through the red pulp of the spleen are removed by splenic macrophages, splenectomy is one possible therapeutic approach to the management of severely affected patients. However, except for hereditary spherocytosis for which the effectiveness of splenectomy has been well documented, the efficacy of splenectomy in other anemias within this group has yet to be determined and there are concerns regarding short- and long-term infectious and thrombotic complications. In light of the priorities identified by the European Hematology Association Roadmap we generated specific recommendations for each disorder, except thalassemia syndromes for which there are other, recent guidelines. Our recommendations are intended to enable clinicians to achieve better informed decisions on disease management by splenectomy, on the type of splenectomy and the possible consequences. As no randomized clinical trials, case control or cohort studies regarding splenectomy in these disorders were found in the literature, recommendations for each disease were based on expert opinion and were subsequently critically revised and modified by the Splenectomy in Rare Anemias Study Group, which includes hematologists caring for both adults and children., SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2017
4. Minihepcidins improve ineffective erythropoiesis and splenomegaly in a new mouse model of adult β-thalassemia major
- Author
-
Casu, Carla, primary, Chessa, Roberta, additional, Liu, Alison, additional, Gupta, Ritama, additional, Drakesmith, Hal, additional, Fleming, Robert, additional, Ginzburg, Yelena Z., additional, MacDonald, Brian, additional, and Rivella, Stefano, additional
- Published
- 2019
- Full Text
- View/download PDF
5. New potential players in hepcidin regulation
- Author
-
Chappell, Maxwell, primary and Rivella, Stefano, additional
- Published
- 2019
- Full Text
- View/download PDF
6. Genetic loss of Tmprss6 alters terminal erythroid differentiation in a mouse model of β-thalassemia intermedia
- Author
-
Stagg, David B., primary, Whittlesey, Rebecca L., additional, Li, Xiuqi, additional, Lozovatsky, Larisa, additional, Gardenghi, Sara, additional, Rivella, Stefano, additional, and Finberg, Karin E., additional
- Published
- 2019
- Full Text
- View/download PDF
7. Short-term administration of JAK2 inhibitors reduces splenomegaly in mouse models of β-thalassemia intermedia and major
- Author
-
Casu, Carla, primary, Presti, Vania Lo, additional, Oikonomidou, Paraskevi Rea, additional, Melchiori, Luca, additional, Abdulmalik, Osheiza, additional, Ramos, Pedro, additional, and Rivella, Stefano, additional
- Published
- 2017
- Full Text
- View/download PDF
8. Minihepcidins improve ineffective erythropoiesis and splenomegaly in a new mouse model of adult β-thalassemia major.
- Author
-
Casu C, Chessa R, Liu A, Gupta R, Drakesmith H, Fleming R, Ginzburg YZ, MacDonald B, and Rivella S
- Subjects
- Animals, Disease Models, Animal, Erythropoiesis, Mice, Hepcidins therapeutic use, Iron Overload drug therapy, Iron Overload etiology, Splenomegaly drug therapy, Splenomegaly etiology, beta-Thalassemia therapy
- Abstract
Minihepcidins are hepcidin agonists that have been previously shown to reverse iron overload and improve erythropoiesis in mice affected by non-transfusion-dependent thalassemia. Given the extreme anemia that occurred with the previous model of transfusion-dependent thalassemia, that model was inadequate for investigating whether minihepcidins can improve red blood cell quality, lifespan and ineffective erythropoiesis. To overcome this limitation, we generated a new murine model of transfusion-dependent thalassemia with severe anemia and splenomegaly, but sufficient red cells and hemoglobin production to test the effect of minihepcidins. Furthermore, this new model demonstrates cardiac iron overload for the first time. In the absence of transfusions, minihepcidins improved red blood cell morphology and lifespan as well as ineffective erythropoiesis. Administration of a minihepcidin in combination with chronic red blood cell transfusion further improved the ineffective erythropoiesis and splenomegaly and reversed cardiac iron overload. These studies indicate that drugs such as minihepcidins have therapeutic potential for patients with transfusion-dependent thalassemia., (Copyright© 2020 Ferrata Storti Foundation.)
- Published
- 2020
- Full Text
- View/download PDF
9. 2'-O-methoxyethyl splice-switching oligos correct splicing from IVS2-745 β-thalassemia patient cells restoring HbA production and chain rebalance.
- Author
-
Dong A, Ghiaccio V, Motta I, Guo S, Peralta R, Freier SM, Watt A, Damle S, Ikawa Y, Jarocha D, Chappell M, Stephanou C, Delbini P, Chen C, Christou S, Kleanthous M, Smith-Whitley K, Manwani D, Casu C, Abdulmalik O, Cappellini MD, Rivella S, and Breda L
- Abstract
β-thalassemia is a disorder caused by altered hemoglobin protein synthesis and affects individuals worldwide. Severe forms of the disease, left untreated, can result in death before the age of 3 years (1). The standard of care consists of chronic and costly palliative treatment by blood transfusion combined with iron chelation. This dual approach suppresses anemia and reduces iron-related toxicities in patients. Allogeneic bone marrow transplant is an option, but limited by the availability of a highly compatible HSC donor. While gene therapy is been explored in several trials, its use is highly limited to developed regions with centers of excellence and well-established healthcare systems (2). Hence, there remains a tremendous unmet medical need to develop alternative treatment strategies for β-thalassemia (3). Occurrence of aberrant splicing is one of the processes that affects β-globin synthesis in β-thalassemia. The (C>G) IVS-2-745 is a splicing mutation within intron 2 of the β-globin gene. It leads to an aberrantly spliced mRNA that incorporates an intron fragment. This results in an in-frame premature termination codon that inhibits β-globin production. Here, we propose the use of uniform 2'-O-methoxyethyl (2'-MOE) splice switching oligos (SSOs) to reverse this aberrant splicing in the pre-mRNA. With these lead SSOs we show aberrant to wild type splice switching. This switching leads to an increase of adult hemoglobin (HbA) up to 80% in erythroid cells from patients with the IVS-2-745 mutation. Furthermore, we demonstrate a restoration of the balance between β-like- and α-globin chains, and up to an 87% reduction in toxic α-heme aggregates. While examining the potential benefit of 2'-MOE-SSOs in a mixed sickle-thalassemic phenotypic setting, we found reduced HbS synthesis and sickle cell formation due to HbA induction. In summary, 2'-MOE-SSOs are a promising therapy for forms of β-thalassemia caused by mutations leading to aberrant splicing.
- Published
- 2019
- Full Text
- View/download PDF
10. Short-term administration of JAK2 inhibitors reduces splenomegaly in mouse models of β-thalassemia intermedia and major.
- Author
-
Casu C, Presti VL, Oikonomidou PR, Melchiori L, Abdulmalik O, Ramos P, and Rivella S
- Subjects
- Animals, Blood Transfusion, Mice, Splenomegaly prevention & control, Janus Kinase 2 antagonists & inhibitors, Protein Kinase Inhibitors therapeutic use, Splenomegaly drug therapy, beta-Thalassemia pathology
- Published
- 2018
- Full Text
- View/download PDF
11. Increased hepcidin in transferrin-treated thalassemic mice correlates with increased liver BMP2 expression and decreased hepatocyte ERK activation.
- Author
-
Chen H, Choesang T, Li H, Sun S, Pham P, Bao W, Feola M, Westerman M, Li G, Follenzi A, Blanc L, Rivella S, Fleming RE, and Ginzburg YZ
- Subjects
- Animals, Antibodies, Neutralizing pharmacology, Bone Morphogenetic Protein 2 agonists, Bone Morphogenetic Protein 2 antagonists & inhibitors, Bone Morphogenetic Protein 2 metabolism, Bone Morphogenetic Protein 6 genetics, Bone Morphogenetic Protein 6 metabolism, Butadienes pharmacology, Cytokines genetics, Cytokines metabolism, Disease Models, Animal, Gene Expression Regulation, Hepatocytes drug effects, Hepatocytes metabolism, Hepcidins agonists, Hepcidins antagonists & inhibitors, Hepcidins metabolism, Humans, Liver drug effects, Liver metabolism, Mice, Mice, Transgenic, Mitogen-Activated Protein Kinase 1 antagonists & inhibitors, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 antagonists & inhibitors, Mitogen-Activated Protein Kinase 3 metabolism, Muscle Proteins genetics, Muscle Proteins metabolism, Nitriles pharmacology, Phosphorylation drug effects, RNA, Messenger antagonists & inhibitors, RNA, Messenger genetics, RNA, Messenger metabolism, Signal Transduction, Smad Proteins genetics, Smad Proteins metabolism, beta-Thalassemia metabolism, beta-Thalassemia pathology, Apoproteins pharmacology, Bone Morphogenetic Protein 2 genetics, Hepcidins genetics, Mitogen-Activated Protein Kinase 1 genetics, Mitogen-Activated Protein Kinase 3 genetics, Transferrin pharmacology, beta-Thalassemia genetics
- Abstract
Iron overload results in significant morbidity and mortality in β-thalassemic patients. Insufficient hepcidin is implicated in parenchymal iron overload in β-thalassemia and approaches to increase hepcidin have therapeutic potential. We have previously shown that exogenous apo-transferrin markedly ameliorates ineffective erythropoiesis and increases hepcidin expression in Hbb(th1/th1) (thalassemic) mice. We utilize in vivo and in vitro systems to investigate effects of exogenous apo-transferrin on Smad and ERK1/2 signaling, pathways that participate in hepcidin regulation. Our results demonstrate that apo-transferrin increases hepcidin expression in vivo despite decreased circulating and parenchymal iron concentrations and unchanged liver Bmp6 mRNA expression in thalassemic mice. Hepatocytes from apo-transferrin-treated mice demonstrate decreased ERK1/2 pathway and increased serum BMP2 concentration and hepatocyte BMP2 expression. Furthermore, hepatocyte ERK1/2 phosphorylation is enhanced by neutralizing anti-BMP2/4 antibodies and suppressed in vitro in a dose-dependent manner by BMP2, resulting in converse effects on hepcidin expression, and hepatocytes treated with MEK/ERK1/2 inhibitor U0126 in combination with BMP2 exhibit an additive increase in hepcidin expression. Lastly, bone marrow erythroferrone expression is normalized in apo-transferrin treated thalassemic mice but increased in apo-transferrin injected wild-type mice. These findings suggest that increased hepcidin expression after exogenous apo-transferrin is in part independent of erythroferrone and support a model in which apo-transferrin treatment in thalassemic mice increases BMP2 expression in the liver and other organs, decreases hepatocellular ERK1/2 activation, and increases nuclear Smad to increase hepcidin expression in hepatocytes., (Copyright© Ferrata Storti Foundation.)
- Published
- 2016
- Full Text
- View/download PDF
12. Combination of Tmprss6- ASO and the iron chelator deferiprone improves erythropoiesis and reduces iron overload in a mouse model of beta-thalassemia intermedia.
- Author
-
Casu C, Aghajan M, Oikonomidou PR, Guo S, Monia BP, and Rivella S
- Subjects
- Animals, Deferiprone, Disease Models, Animal, Erythropoiesis genetics, Membrane Proteins genetics, Membrane Proteins metabolism, Mice, Serine Endopeptidases genetics, Serine Endopeptidases metabolism, beta-Thalassemia genetics, beta-Thalassemia metabolism, Erythropoiesis drug effects, Iron Chelating Agents pharmacology, Membrane Proteins antagonists & inhibitors, Pyridones pharmacology, beta-Thalassemia drug therapy
- Published
- 2016
- Full Text
- View/download PDF
13. β-thalassemias: paradigmatic diseases for scientific discoveries and development of innovative therapies.
- Author
-
Rivella S
- Subjects
- Animals, Erythropoiesis genetics, Humans, Iron metabolism, Phenotype, Therapies, Investigational, beta-Globins metabolism, beta-Thalassemia diagnosis, beta-Globins genetics, beta-Thalassemia etiology, beta-Thalassemia therapy
- Abstract
β-thalassemias are monogenic disorders characterized by defective synthesis of the β-globin chain, one of the major components of adult hemoglobin. A large number of mutations in the β-globin gene or its regulatory elements have been associated with β-thalassemias. Due to the complexity of the regulation of the β-globin gene and the role of red cells in many physiological processes, patients can manifest a large spectrum of phenotypes, and clinical requirements vary from patient to patient. It is important to consider the major differences in the light of potential novel therapeutics. This review summarizes the main discoveries and mechanisms associated with the synthesis of β-globin and abnormal erythropoiesis, as well as current and novel therapies., (Copyright© Ferrata Storti Foundation.)
- Published
- 2015
- Full Text
- View/download PDF
14. Non-transfusion-dependent thalassemias.
- Author
-
Musallam KM, Rivella S, Vichinsky E, and Rachmilewitz EA
- Subjects
- Blood Transfusion, Gene-Environment Interaction, Humans, Phenotype, Thalassemia diagnosis, Thalassemia etiology, Thalassemia therapy
- Abstract
Non-transfusion-dependent thalassemias include a variety of phenotypes that, unlike patients with beta (β)-thalassemia major, do not require regular transfusion therapy for survival. The most commonly investigated forms are β-thalassemia intermedia, hemoglobin E/β-thalassemia, and α-thalassemia intermedia (hemoglobin H disease). However, transfusion-independence in such patients is not without side effects. Ineffective erythropoiesis and peripheral hemolysis, the hallmarks of disease process, lead to a variety of subsequent pathophysiologies including iron overload and hypercoagulability that ultimately lead to a number of serious clinical morbidities. Thus, prompt and accurate diagnosis of non-transfusion-dependent thalassemia is essential to ensure early intervention. Although several management options are currently available, the need to develop more novel therapeutics is justified by recent advances in our understanding of the mechanisms of disease. Such efforts require wide international collaboration, especially since non-transfusion-dependent thalassemias are no longer bound to low- and middle-income countries but have spread to large multiethnic cities in Europe and the Americas due to continued migration.
- Published
- 2013
- Full Text
- View/download PDF
15. The murine growth differentiation factor 15 is not essential for systemic iron homeostasis in phlebotomized mice.
- Author
-
Casanovas G, Vujić Spasic M, Casu C, Rivella S, Strelau J, Unsicker K, and Muckenthaler MU
- Subjects
- Animals, Bone Marrow metabolism, Erythrocyte Indices, Female, Growth Differentiation Factor 15 genetics, Hepcidins genetics, Hepcidins metabolism, Iron blood, Liver metabolism, Male, Mice, Mice, Knockout, Phlebotomy, RNA, Messenger genetics, RNA, Messenger metabolism, Spleen metabolism, Growth Differentiation Factor 15 metabolism, Homeostasis, Iron metabolism
- Abstract
In conditions of increased erythropoiesis, expression of hepcidin, the master regulator of systemic iron homeostasis, is decreased to allow for the release of iron into the blood stream from duodenal enterocytes and macrophages. It has been suggested that hepcidin suppression is controlled by growth differentiation factor 15 (GDF15), a member of the transforming growth factor-β superfamily of cytokines that is secreted from developing erythroblasts. In this study, we analyzed iron-related parameters in mice deficient for GDF15 under steady-state conditions and in response to increased erythropoietic activity induced by blood loss. We demonstrate that GDF15 suppresses the hepatic mRNA expression of some BMP/TGFβ target genes but not of hepcidin, and show that GDF15 is not required to balance iron homeostasis in response to blood loss.
- Published
- 2013
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.