16 results on '"Orecchia V"'
Search Results
2. Unplanned pregnancy in women with beta-thalassaemia treated with luspatercept.
- Author
-
Zaccheddu E, Zappu A, Barella S, Clemente MG, Orecchia V, Pilia MP, Piras S, Pitturru C, Scarano M, and Origa R
- Subjects
- Humans, Female, Pregnancy, Adult, Immunoglobulin Fc Fragments therapeutic use, Immunoglobulin Fc Fragments adverse effects, Activin Receptors, Type II therapeutic use, Pregnancy Complications, Hematologic drug therapy, beta-Thalassemia drug therapy, beta-Thalassemia therapy, beta-Thalassemia complications, Recombinant Fusion Proteins therapeutic use, Pregnancy, Unplanned
- Published
- 2024
- Full Text
- View/download PDF
3. Nephrological Complications in Hemoglobinopathies: SITE Good Practice.
- Author
-
Ruffo GB, Russo R, Casini T, Lombardini L, Orecchia V, Voi V, Origa R, Forni GL, Marchetti M, Gigante A, Garibotto G, Maggio A, and De Franceschi L
- Abstract
Background: Hemoglobinopathies, among which thalassemic syndromes (transfusion-dependent and non-transfusion dependent thalassemias) and sickle cell disease (SCD), are the most widespread monogenic diseases worldwide. Hemoglobinopathies are endemic and spread-out all-over Italy, as result of internal and external migration flows. Nowadays, the increase therapeutic options associated to the general aging of patients with hemoglobinopathies related to the improvement in clinical management, contribute to the abnormalities in kidney function going from blood and urine test alterations to chronic kidney disease and end stage renal disease., Methods: Here, we carried out a revision of the literature as panel of recognized experts in hemoglobinopathies with the consultancy and the revision of two nephrologists on kidney alteration and kidney disease in patients with TDT, NTDT and SCD. This is part of the action of the Italian society for the study of thalassemia and hemoglobinopties (SITE). The purpose of this "good practice (GP)" is to provide recommendations for follow-up and therapy for the management of kidney alterations in patients with TDT, NTDT and SCD. The literature review covers the period 1.1.2016 to 31.12.2022. In consideration of the rarity of these diseases, the analysis was extended from 5 to 7 years. Moreover, in the absence of relevant scientific papers in the identified time frame, we referred to pivotal or population studies, when available. Finally, in the absence of evidence-based data from prospective and randomized trials, the authors had to refer to expert opinion (expert consensus) for many topics., Results: We generated question and answer boxes to offer a friendly consultation, using color code strategy and focused answers., Conclusions: The present GP will help in improving the clinical management, and the quality of care of patients with hemoglobinopathies.
- Published
- 2023
- Full Text
- View/download PDF
4. Long-Term Health-Related Quality of Life and Clinical Outcomes in Patients with β-Thalassemia after Splenectomy.
- Author
-
Caocci G, Mulas O, Barella S, Orecchia V, Mola B, Costa A, Efficace F, and La Nasa G
- Abstract
Few data are available on the efficacy and safety of splenectomy in patients with transfusion-dependent Beta-Thalassemia Major (β-TM) and on its impact on a patient's health-related quality of life (HRQoL). We examined the long-term HRQoL of adult patients with β-TM in comparison with those treated with medical therapy by using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). We also evaluated the safety and efficacy of splenectomy. Overall, 114 patients with a median age of 41 years (range 18-62) were enrolled in this cross-sectional study. Twenty-nine patients underwent splenectomy (25.4%) at a median age of 12 years (range 1-32). The median follow-up after splenectomy was 42 years (range 6-55). No statistically significant differences were observed in any of the scales of the SF-36 between splenectomized and not-splenectomized patients. The majority of surgical procedures (96.6%) were approached with open splenectomy. Post-splenectomy complications were reported in eight patients (27.5%): four overwhelming infections, three with pulmonary hypertension, and one with thrombosis. A significantly higher prevalence of cardiovascular comorbidities (58.6 vs. 21.2%, p < 0.001) and diabetes (17.2 vs. 3.5%, p = 0.013) was observed in splenectomized patients. These patients, however, required fewer red blood cell units per month, with only 27.6% of them transfusing more than 1 unit per month, compared with 72.9% of the not-splenectomized group. Overall, our data suggest that physicians should carefully consider splenectomy as a possible treatment option in patients with β-TM.
- Published
- 2023
- Full Text
- View/download PDF
5. Safety and Efficacy of the New Combination Iron Chelation Regimens in Patients with Transfusion-Dependent Thalassemia and Severe Iron Overload.
- Author
-
Origa R, Cinus M, Pilia MP, Gianesin B, Zappu A, Orecchia V, Clemente MG, Pitturru C, Denotti AR, Corongiu F, Piras S, and Barella S
- Abstract
The aim of this study is the evaluation of the safety and the efficacy of long-term combination therapy deferasirox plus desferrioxamine and deferasirox plus deferiprone in a large group of transfusion-dependent thalassemia patients with high values of serum ferritin and/or magnetic resonance, indicative of severe liver and cardiac iron accumulation. Sixteen adults with transfusion-dependent thalassemia were treated simultaneously with deferasirox plus desferrioxamine, while another 42 patients (seven children) were treated with deferasirox plus deferiprone. The hepatic and cardiac iron overload was assessed prior to treatment and then annually with magnetic resonance imaging, and the serum ferritin was measured monthly. Adverse events were checked at each transfusion visit. The safety of both the combinations was consistent with established monotherapies. Both treatments were able to decrease the serum ferritin and liver iron concentration over time, depending on the level of compliance with therapy. Cardiac iron measured as R2* did not significantly change in patients treated with deferasirox plus desferrioxamine. Most patients with MRI indicative of myocardial siderosis at the beginning of treatment reached normal values of cardiac iron at the last determination if treated with deferasirox plus desferrioxamine. The greatest limitation of these therapies was low patient adherence to the two drugs, which is not surprising considering that the need for an intensive chelation is generally linked to previous issues of compliance.
- Published
- 2022
- Full Text
- View/download PDF
6. STAT3 localizes to the ER, acting as a gatekeeper for ER-mitochondrion Ca 2+ fluxes and apoptotic responses.
- Author
-
Avalle L, Camporeale A, Morciano G, Caroccia N, Ghetti E, Orecchia V, Viavattene D, Giorgi C, Pinton P, and Poli V
- Subjects
- Calcium metabolism, Cell Death genetics, Cell Nucleus genetics, Cell Nucleus metabolism, Endoplasmic Reticulum genetics, Endoplasmic Reticulum Stress genetics, Energy Metabolism genetics, Gene Expression genetics, Humans, Mitochondria genetics, Mitochondria metabolism, Proteolysis, Apoptosis genetics, Calcium Signaling genetics, Inositol 1,4,5-Trisphosphate Receptors genetics, STAT3 Transcription Factor genetics
- Abstract
STAT3 is an oncogenic transcription factor exerting its functions both as a canonical transcriptional activator and as a non-canonical regulator of energy metabolism and mitochondrial functions. While both activities are required for cell transformation downstream of different oncogenic stimuli, they rely on different post-translational activating events, namely phosphorylation on either Y705 (nuclear activities) or S727 (mitochondrial functions). Here, we report the discovery of the unexpected STAT3 localization to the endoplasmic reticulum (ER), from where it modulates ER-mitochondria Ca
2+ release by interacting with the Ca2+ channel IP3R3 and facilitating its degradation. The release of Ca2+ is of paramount importance for life/death cell decisions, as excessive Ca2+ causes mitochondrial Ca2+ overload, the opening of the mitochondrial permeability transition pore, and the initiation of the intrinsic apoptotic program. Indeed, STAT3 silencing enhances ER Ca2+ release and sensitivity to apoptosis following oxidative stress in STAT3-dependent mammary tumor cells, correlating with increased IP3R3 levels. Accordingly, basal-like mammary tumors, which frequently display constitutively active STAT3, show an inverse correlation between IP3R3 and STAT3 protein levels. These results suggest that STAT3-mediated IP3R3 downregulation in the ER crucially contributes to its anti-apoptotic functions via modulation of Ca2+ fluxes.- Published
- 2019
- Full Text
- View/download PDF
7. SP1 and STAT3 Functionally Synergize to Induce the RhoU Small GTPase and a Subclass of Non-canonical WNT Responsive Genes Correlating with Poor Prognosis in Breast Cancer.
- Author
-
Monteleone E, Orecchia V, Corrieri P, Schiavone D, Avalle L, Moiso E, Savino A, Molineris I, Provero P, and Poli V
- Abstract
Breast cancer is a heterogeneous disease whose clinical management is very challenging. Although specific molecular features characterize breast cancer subtypes with different prognosis, the identification of specific markers predicting disease outcome within the single subtypes still lags behind. Both the non-canonical Wingless-type MMTV Integration site (WNT) and the Signal Transducer and Activator of Transcription (STAT)3 pathways are often constitutively activated in breast tumors, and both can induce the small GTPase Ras Homolog Family Member U RhoU . Here we show that RhoU transcription can be triggered by both canonical and non-canonical WNT ligands via the activation of c-JUN N-terminal kinase (JNK) and the recruitment of the Specificity Protein 1 (SP1) transcription factor to the RhoU promoter, identifying for the first time SP1 as a JNK-dependent mediator of WNT signaling. RhoU down-regulation by silencing or treatment with JNK, SP1 or STAT3 inhibitors leads to impaired migration and invasion in basal-like MDA-MB-231 and BT-549 cells, suggesting that STAT3 and SP1 can cooperate to induce high RhoU expression and enhance breast cancer cells migration. Moreover, in vivo concomitant binding of STAT3 and SP1 defines a subclass of genes belonging to the non-canonical WNT and the Interleukin (IL)-6/STAT3 pathways and contributing to breast cancer aggressiveness, suggesting the relevance of developing novel targeted therapies combining inhibitors of the STAT3 and WNT pathways or of their downstream mediators.
- Published
- 2019
- Full Text
- View/download PDF
8. Quality of life in Sardinian patients with transfusion-dependent Thalassemia: a cross-sectional study.
- Author
-
Floris F, Comitini F, Leoni G, Moi P, Morittu M, Orecchia V, Perra M, Pilia MP, Zappu A, Casini MR, and Origa R
- Subjects
- Adolescent, Adult, Aged, Cross-Sectional Studies, Female, Humans, Italy, Male, Middle Aged, Patient Compliance, Surveys and Questionnaires, World Health Organization, Young Adult, Blood Transfusion, Quality of Life psychology, Thalassemia pathology, Thalassemia psychology, Thalassemia therapy
- Abstract
Purpose: The aim of this study has been to evaluate the physical, psychological, and social well-being in a large group of Sardinian adult patients with transfusion-dependent beta-Thalassemia when compared with a group of healthy subjects of the same age and geographical extraction., Methods: Male or female patients ≥ 18 years of age with Thalassemia major on regular transfusion at Thalassemia Center in Cagliari (Italy) were requested to complete the World Health Organization Quality of life-BREF (WHOQOL-BREF) questionnaire. The WHOQOL-BREF was also made available online to age- and sex-matched non-thalassemic adult subjects living in Sardinia., Results: Two hundred and seven subjects with Thalassemia were invited to participate in the study. The questionnaire was also completed by 211 age- and sex-matched non-thalassemic subjects living in Sardinia. Scores suggestive of a good quality of life were obtained in all the areas investigated. Thalassemia patients had scores at least as good as those of non-thalassemic subjects in all items and the percentage of those with a score ≥ 60 was higher among patients. The analysis of demographic actually highlights that the disease has a little effect on their personal and social lives. There was a positive association between subjective well-being and effective clinical conditions. Moreover, the association between health perception and adherence to treatment suggests that compliance with treatment contributes to the well-being of the patient, both physically and psychologically., Conclusions: Adult subjects with Thalassemia who live in Western countries have a good quality of life in accordance with the advances in the management of the disease.
- Published
- 2018
- Full Text
- View/download PDF
9. Hematological phenotypes in children according to the α-globin genotypes.
- Author
-
Origa R, Barella S, Paglietti ME, Anni F, Danjou F, Denotti AR, Desogus MF, Loi D, Orecchia V, Sollaino MC, and Moi P
- Subjects
- Adolescent, Biomarkers, Child, Child, Preschool, Erythrocyte Indices, Female, Fetal Hemoglobin genetics, Genetic Predisposition to Disease, Humans, Infant, Male, alpha-Thalassemia blood, alpha-Thalassemia diagnosis, alpha-Thalassemia genetics, Genetic Association Studies, Genotype, Hematopoiesis genetics, Phenotype, alpha-Globins genetics
- Abstract
Limited information is available on the hematological characterization of the α-thalassemia carrier in pediatric age. The objective of this report was to evaluate the red cell indices according to the α-globin genotype in a cohort of children evaluated in Sardinia. Moreover, we verified the frequency of different α-globin genotypes in this cohort. A total of 453 subjects were investigated for hematological indices and for the most common α-globin defects present in Sardinia. Of them, 352 with HbA2≤3.2%, and no iron deficiency anemia were taken into consideration to evaluate the red cell indices according to the α-globin genotype in pediatric age. A total of 11 different α-genotypes were detected, confirming the wide heterogeneity of α-thalassemia in Sardinia. Moreover, our results showed that the hematological parameters in normal children may be conditioned by the clinically occult coinheritance of mild α-thalassemia alleles as already described in the adult population while microcytosis and hypocromia in children without iron deficiency should suggest the coexistence of two α-globin defects. We concluded that recognizing the α-globin gene mutations for a particular population with their particular red cell indices may help pediatricians to perform a correct diagnosis distinguishing among physiological and pathological types of microcytosis and hypocromia., (Copyright © 2017. Published by Elsevier Inc.)
- Published
- 2018
- Full Text
- View/download PDF
10. Earlier initiation of transfusional and iron chelation therapies in recently born children with transfusion-dependent thalassemia.
- Author
-
Origa R, Tatti F, Zappu A, Leoni GB, Dessì C, Moi P, Morittu M, Orecchia V, Denotti AR, Pilia MP, Anni F, Perra M, Casini MR, and Barella S
- Subjects
- Adolescent, Adult, Age Factors, Child, Child, Preschool, Female, Humans, Infant, Male, Thalassemia mortality, Blood Transfusion, Iron Chelating Agents administration & dosage, Thalassemia therapy
- Published
- 2017
- Full Text
- View/download PDF
11. Causes of hospital admission in children and adults with transfusion-dependent thalassemia in Sardinia, 2000-2015.
- Author
-
Origa R, Anni F, Mereu L, Follesa I, Campus S, Dessì C, Foschini ML, Leoni G, Moi P, Morittu M, Orecchia V, Perra M, Zappu A, and Podda RA
- Subjects
- Adolescent, Adult, Age Factors, Child, Child, Preschool, Comorbidity, Diagnosis-Related Groups, Female, Heart Diseases epidemiology, Heart Diseases etiology, Heart Diseases prevention & control, Humans, Infant, Iron Chelating Agents adverse effects, Iron Chelating Agents therapeutic use, Iron Overload drug therapy, Iron Overload etiology, Italy epidemiology, Male, Mesenteric Lymphadenitis etiology, Middle Aged, Retrospective Studies, Thalassemia complications, Thalassemia therapy, Yersinia Infections etiology, Young Adult, Blood Transfusion, Hospitalization, Patient Admission, Thalassemia epidemiology
- Published
- 2017
- Full Text
- View/download PDF
12. Current growth patterns in children and adolescents with thalassemia major.
- Author
-
Origa R, Danjou F, Orecchia V, Zappu A, Dessì C, Foschini ML, Leoni GB, Moi P, Morittu M, Demurtas A, and Loche S
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Male, Adolescent Development, Blood Transfusion, Body Height, Child Development, Deferoxamine administration & dosage, beta-Thalassemia physiopathology, beta-Thalassemia therapy
- Published
- 2016
- Full Text
- View/download PDF
13. A relaxometric method for the assessment of intestinal permeability based on the oral administration of gadolinium-based MRI contrast agents.
- Author
-
Gianolio E, Boffa C, Orecchia V, Bardini P, Catanzaro V, Poli V, and Aime S
- Subjects
- Administration, Oral, Animals, Colitis pathology, Colon pathology, Dextran Sulfate, Disease Models, Animal, Mice, Inbred BALB C, Permeability, Reproducibility of Results, Contrast Media administration & dosage, Gadolinium administration & dosage, Intestines pathology, Magnetic Resonance Imaging methods
- Abstract
Herein, a new relaxometric method for the assessment of intestinal permeability based on the oral administration of clinically approved gadolinium (Gd)-based MRI contrast agents (CAs) is proposed. The fast, easily performed and cheap measurement of the longitudinal water proton relaxation rate (R1) in urine reports the amount of paramagnetic probe that has escaped the gastrointestinal tract. The proposed method appears to be a compelling alternative to the available methods for the assessment of intestinal permeability. The method was tested on the murine model of dextran sulfate sodium (DSS)-induced colitis in comparison with healthy mice. Three CAs were tested, namely ProHance®, MultiHance® and Magnevist®. Urine was collected for 24 h after the oral ingestion of the Gd-containing CA at day 3-4 (severe damage stage) and day 8-9 (recovery stage) after treatment with DSS. The Gd content in urine measured by (1)H relaxometry was confirmed by inductively coupled plasma-mass spectrometry (ICP-MS). The extent of urinary excretion was given as a percentage of excreted Gd over the total ingested dose. The method was validated by comparing the results obtained with the established methodology based on the lactulose/mannitol and sucralose tests. For ProHance and Magnevist, the excreted amounts in the severe stage of damage were 2.5-3 times higher than in control mice. At the recovery stage, no significant differences were observed with respect to healthy mice. Overall, a very good correlation with the lactulose/mannitol and sucralose results was obtained. In the case of MultiHance, the percentage of excreted Gd complex was not significantly different from that of control mice in either the severe or recovery stages. The difference from ProHance and Magnevist was explained on the basis of the (known) partial biliary excretion of MultiHance in mice., (Copyright © 2016 John Wiley & Sons, Ltd.)
- Published
- 2016
- Full Text
- View/download PDF
14. The apical ectodermal ridge of the mouse model of ectrodactyly Dlx5;Dlx6-/- shows altered stratification and cell polarity, which are restored by exogenous Wnt5a ligand.
- Author
-
Conte D, Garaffo G, Lo Iacono N, Mantero S, Piccolo S, Cordenonsi M, Perez-Morga D, Orecchia V, Poli V, and Merlo GR
- Subjects
- Animals, Cell Polarity drug effects, Cell Polarity physiology, Disease Models, Animal, Down-Regulation, Ectoderm metabolism, Ectoderm pathology, Homeodomain Proteins metabolism, JNK Mitogen-Activated Protein Kinases metabolism, Limb Deformities, Congenital drug therapy, Limb Deformities, Congenital metabolism, Mesoderm metabolism, Mice, Mice, Knockout, Trans-Activators genetics, Wnt Signaling Pathway, Wnt-5a Protein biosynthesis, Wnt-5a Protein deficiency, Wnt-5a Protein genetics, beta Catenin metabolism, Homeodomain Proteins genetics, Limb Deformities, Congenital genetics, Limb Deformities, Congenital pathology, Wnt-5a Protein pharmacology
- Abstract
The congenital malformation split hand/foot (SHFM) is characterized by missing central fingers and dysmorphology or fusion of the remaining ones. Type-1 SHFM is linked to deletions/rearrangements of the DLX5-DLX6 locus and point mutations in the DLX5 gene. The ectrodactyly phenotype is reproduced in mice by the double knockout (DKO) of Dlx5 and Dlx6. During limb development, the apical ectodermal ridge (AER) is a key-signaling center responsible for early proximal-distal growth and patterning. In Dlx5;6 DKO hindlimbs, the central wedge of the AER loses multilayered organization and shows down-regulation of FGF8 and Dlx2. In search for the mechanism, we examined the non-canonical Wnt signaling, considering that Dwnt-5 is a target of distalless in Drosophila and the knockout of Wnt5, Ryk, Ror2 and Vangl2 in the mouse causes severe limb malformations. We found that in Dlx5;6 DKO limbs, the AER expresses lower levels of Wnt5a, shows scattered β-catenin responsive cells and altered basolateral and planar cell polarity (PCP). The addition of Wnt5a to cultured embryonic limbs restored the expression of AER markers and its stratification. Conversely, the inhibition of the PCP molecule c-jun N-terminal kinase caused a loss of AER marker expression. In vitro, the addition of Wnt5a on mixed primary cultures of embryonic ectoderm and mesenchyme was able to confer re-polarization. We conclude that the Dlx-related ectrodactyly defect is associated with the loss of basoapical and PCP, due to reduced Wnt5a expression and that the restoration of the Wnt5a level is sufficient to partially reverts AER misorganization and dysmorphology., (© The Author 2015. Published by Oxford University Press.)
- Published
- 2016
- Full Text
- View/download PDF
15. Constitutive STAT3 activation in epidermal keratinocytes enhances cell clonogenicity and favours spontaneous immortalization by opposing differentiation and senescence checkpoints.
- Author
-
Orecchia V, Regis G, Tassone B, Valenti C, Avalle L, Saoncella S, Calautti E, and Poli V
- Subjects
- Animals, Animals, Newborn, Cell Movement, Cell Proliferation, Glycolysis, Hyperplasia metabolism, Keratinocytes cytology, Mice, Mice, Transgenic, Real-Time Polymerase Chain Reaction, Skin metabolism, Skin Aging, Stem Cells cytology, beta-Galactosidase metabolism, Cell Differentiation, Cellular Senescence, Epidermal Cells, Keratinocytes metabolism, STAT3 Transcription Factor metabolism
- Abstract
STAT3, a pleiotropic transcription factor acting downstream of cytokines and growth factors, is known to enhance proliferation, migration, invasion and aerobic glycolysis in tumors upon aberrant activation. In the murine epidermis, STAT3 is necessary for experimentally induced carcinogenesis. Skin tumorigenesis is conversely enhanced by overexpression in keratinocytes of the constitutively active STAT3C mutant, which also induces robust, psoriasis-like epidermal hyperplasia. We show here that STAT3C expression at physiological levels in knock-in mice leads to mild epidermal hyperplasia and attenuated expression of terminal differentiation markers. Altered differentiation is confirmed in isolated primary epidermal keratinocytes in vitro, correlating with enhanced proliferative and clonogenic potential, attenuated senescence and, strikingly, high-frequency spontaneous immortalization. These results suggest that moderate levels of continuous STAT3 activation, which closely resemble those triggered by chronic inflammation or persistent growth factor stimulation, may establish a preneoplastic state in part by promoting the escape of epidermal progenitor cells from differentiation and senescence checkpoints., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2015
- Full Text
- View/download PDF
16. STAT3β controls inflammatory responses and early tumor onset in skin and colon experimental cancer models.
- Author
-
Marino F, Orecchia V, Regis G, Musteanu M, Tassone B, Jon C, Forni M, Calautti E, Chiarle R, Eferl R, and Poli V
- Abstract
Chronic inflammation is a well-recognized pathogenic factor in tumor initiation and progression. Mice lacking the pro-oncogenic transcription factor STAT3 were shown to be protected from both colitis-associated and epidermal cancers induced by the AOM/DSS and DMBA/TPA protocols, respectively. However, these murine models did not distinguish between the two STAT3 isoforms, the full-length STAT3α, believed to exert most pro-oncogenic functions attributed to STAT3, and the shorter STAT3β, often referred to as a dominant-negative, but possessing specific transcriptional activities. Here we assessed the contribution of STAT3β to inflammation-driven tumorigenesis making use of mice lacking this isoform, but still expressing STAT3α (STAT3(Δβ/Δβ)). We show that the lack of STAT3β leads to exacerbated acute responses to both TPA and DSS, thus confirming its anti-inflammatory role. Enhanced inflammation correlates with earlier tumor onset in both the epidermis and the intestine in STAT3(Δβ/Δβ) mice. In contrast, overall tumor development and final tumor burden were unaffected. These results suggest that STAT3β, by limiting inflammation during the initial phases of tumorigenesis, contributes to tissue homeostasis and counteracts malignant transformation and initial tumor growth. Accordingly, the balance between the two STAT3 isoforms, likely determined by the complex signaling networks shaping the tumor microenvironment and driving tumor transformation and progression, is apparently crucial to determine the initial tumor transformation rates in inflammation-associated cancers.
- Published
- 2014
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.