16 results on '"Finotto, S."'
Search Results
2. P1256: A NOVEL DROP‐OFF DIGITAL PCR ASSAY FOR CXCR4 MUTATION SCREENING IN IGM GAMMOPATHIES: FIRST DATA FROM THE FONDAZIONE ITALIANA LINFOMI BIO‐WM STUDY.
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Drandi, D., Ferrante, M., Zibellini, S., Marcheselli, L., Cappello, E., Borriero, M., Ragaini, S., Dogliotti, I., Varraso, C., Cavallo, F., Ferrari, A., Merli, M., Zamprogna, G., Laurenti, L., Tomasetti, S., Cencini, E., Loseto, G., Finotto, S., Marchetti, M., and Re, F.
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- 2022
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3. NFATc1 deletion in T lymphocytes inhibits the allergic trait in a murine model of asthma.
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Koch, S., Reppert, S., and Finotto, S.
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T cells ,MOUSE leukemia ,ASTHMA ,HOMEOSTASIS ,TRANSCRIPTION factors - Abstract
Background NFATc1 isoforms are highly regulated in peripheral T cells where they contribute to the effector function and cell homeostasis. Objective Here, we investigated the role of NFATc1 in asthma and in T cells. Methods In a murine model of allergic asthma, we analysed differences in T-cell development in this allergic disease model, between wild-type and NFATc1 conditional knockout mice. Thus, we performed quantitative real-time PCR to investigate the mRNA expression of Th2-associated genes as well as genes that are involved in IgE immunoglobulin class-switch. Additionally, we used ELISA, Western blot and flow cytometry ( FACS) to analyse protein concentrations of Th1-, Th2- and Th17-specific transcription factors and cytokines and the Th2 chemokine, thymus and activation-regulated chemokine/chemokine ligand 17 ( TARC/ CCL17) by ELISA. Results Mice lacking NFATc1 in CD4
+ T cells display a significant reduction in lung Th2 and Th17 as well as an increase of Th1 cells in an experimental asthma model. Additionally, Batf gene, a recently described transcription factor of the Th2 and Th17 cell differentiation as well as a key T and B transcription factor involved in the IgE immunoglobulin class-switch, was found decreased in the lungs of these mice. As a consequence, serum OVA-specific IgE and IgG1 levels were found significantly decreased after allergen exposure and in the absence of NFATc1 in T cells in experimental allergic asthma. Conclusions and Clinical Relevance Targeting NFATc1 in T lymphocytes ameliorated the allergic trait in the airways of NFATc1fl/fl x CD4Cre mice. NFATc1 emerges as a novel target for anti-allergy intervention. [ABSTRACT FROM AUTHOR]- Published
- 2015
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4. MICROENVIRONMENTAL CONTROL OF INFLAMMATORY CELL DIFFERENTIATION.
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Denburg, J. A., Dolovich, J., Kanai, N., Finotto, S., Ohno, I., Marshall, J., and Jordana, M.
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CELL differentiation ,INFLAMMATION ,CELLS ,CYTOKINES ,ENDOTOXINS ,MORPHOGENESIS - Abstract
The article presents a discussion related to the microenvironmental control of inflammatory cell differentiation. A wide body of information now exists on hemopoletic and proinflammatory cytokine production by structural cells of the microenvironment included among these are epithelial cells, endothelial cells and fibroblasts which can, either constitutively or upon stimulation with other cytokines lipopolysaccharide, express the genes as well as yet unidentified cytokines with prominent cell differentiation-inducing activities.
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- 1993
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5. Addressing adverse synergies between chemical and biological pollutants at schools-The 'SynAir-G' hypothesis.
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Papadopoulos NG, Akdis CA, Akdis M, Damialis A, Esposito G, Fergadiotou I, Goroncy C, Guitton P, Gotua M, Erotokritou K, Jartti T, Murray C, Nenes A, Nikoletseas S, Finotto S, Pandis SN, Ramiconi V, Simpson A, Soudunsaari A, Stårbröst A, Staiano M, Varriale A, Xepapadaki P, Zuberbier T, and Annesi-Maesano I
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- Child, Humans, Particulate Matter, Environmental Monitoring, Air Pollution, Indoor adverse effects, Environmental Pollutants, Air Pollutants adverse effects, Air Pollutants analysis, Asthma epidemiology, Asthma etiology
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While the number and types of indoor air pollutants is rising, much is suspected but little is known about the impact of their potentially synergistic interactions, upon human health. Gases, particulate matter, organic compounds but also allergens and viruses, fall within the 'pollutant' definition. Distinct populations, such as children and allergy and asthma sufferers are highly susceptible, while a low socioeconomic background is a further susceptibility factor; however, no specific guidance is available. We spend most of our time indoors; for children, the school environment is of paramount importance and potentially amenable to intervention. The interactions between some pollutant classes have been studied. However, a lot is missing with respect to understanding interactions between specific pollutants of different classes in terms of concentrations, timing and sequence, to improve targeting and upgrade standards. SynAir-G is a European Commission-funded project aiming to reveal and quantify synergistic interactions between different pollutants affecting health, from mechanisms to real life, focusing on the school setting. It will develop a comprehensive and responsive multipollutant monitoring system, advance environmentally friendly interventions, and disseminate the generated knowledge to relevant stakeholders in accessible and actionable formats. The aim of this article it to put forward the SynAir-G hypothesis, and describe its background and objectives., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
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- 2024
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6. Effect of Haemophilus influenzae, Streptococcus pneumoniae and influenza vaccinations on infections, immune response and asthma control in preschool children with asthma.
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Gao YD, Xepapadaki P, Cui YW, Stanic B, Maurer DJ, Bachert C, Zhang N, Finotto S, Chalubinski M, Lukkarinen H, Passioti M, Graser A, Jartti T, Kowalski M, Ogulur I, Shi ZW, Akdis M, Papadopoulos NG, and Akdis CA
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- Humans, Child, Preschool, Infant, Streptococcus pneumoniae, Haemophilus influenzae, Prospective Studies, Leukocytes, Mononuclear, Cytokines, Immunity, Vaccination, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Anti-Inflammatory Agents, Influenza, Human prevention & control, Asthma, Respiratory Tract Infections microbiology
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Background: Haemophilus influenzae (H. influenzae), Streptococcus pneumoniae (pneumococcus) and influenza vaccines are administered in children to prevent infections caused by these pathogens. The benefits of vaccination for asthma control in children and the elicited immune response are not fully understood. This study aimed to investigate the impact of these vaccinations on respiratory infections, asthma symptoms, asthma severity and control status, pathogen colonization and in vitro immune responses to different stimulants mimicking infections in asthmatic children., Methods: Children aged 4-6 years were recruited into the multicentre prospective PreDicta study conducted across five European countries. Information about vaccination history, infections, antibiotic use, inhaled corticosteroid (ICS) use and asthma symptoms in the last 12 months were obtained from questionnaires of the study. Nasopharyngeal samples were collected at the first visit to assess bacterial and viral colonization, and venous blood for isolation of peripheral blood mononuclear cells (PBMCs). The PBMCs were stimulated with phytohemagglutinin, R848, Poly I:C and zymosan. The levels of 22 cytokines and chemokines were measured in cell culture supernatants using a luminometric multiplex assay., Results: One-hundred and forty asthmatic preschool children (5.3 ± 0.7 years) and 53 healthy children (5.0 ± 0.8 years) from the PreDicta cohort were included in the current study. Asthmatic children were associated with more frequent upper and lower respiratory infections, and more frequent and longer duration of antibiotic use compared with healthy children. In asthmatic children, sufficient H. influenzae vaccination was associated with a shorter duration of upper respiratory infection (URI) and overall use and average dose of ICS. The airway colonization was characterized by less pneumococcus and more rhinovirus. Pneumococcal vaccination was associated with a reduction in the use rate and average dose of ICS, improved asthma control, and less human enterovirus and more H. influenzae and rhinovirus (RV) airway colonization. Influenza vaccination in the last 12 months was associated with a longer duration of URI, but with a decrease in the occurrence of lower respiratory infection (LRI) and the duration of gastrointestinal (GI) infection and antibiotic use. Asthmatic preschoolers vaccinated with H. influenzae, pneumococcus or influenza presented higher levels of Th1-, Th2-, Th17- and regulatory T cells (Treg)-related cytokines in unstimulated PBMCs. Under stimulation, PBMCs from asthmatic preschoolers with pneumococcal vaccination displayed a predominant anti-inflammatory immune response, whereas PBMCs from asthmatic children with sufficient H. influenzae or influenza vaccination were associated with both pro- and anti-inflammatory immune responses., Conclusion: In asthmatic preschoolers, the standard childhood vaccinations to common respiratory pathogens have beneficial effects on asthma control and may modulate immune responses relevant to asthma pathogenesis., (© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
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- 2023
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7. Respiratory virome profiles reflect antiviral immune responses.
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Rovira Rubió J, Megremis S, Pasioti M, Lakoumentas J, Constantinides B, Xepapadaki P, Bachert C, Finotto S, Jartti T, Andreakos E, Stanic B, Akdis CA, Akdis M, and Papadopoulos NG
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- Child, Preschool, Child, Humans, Virome, Leukocytes, Mononuclear, Interferons, Immunity, Antiviral Agents, Asthma
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Background: From early life, respiratory viruses are implicated in the development, exacerbation and persistence of respiratory conditions such as asthma. Complex dynamics between microbial communities and host immune responses shape immune maturation and homeostasis, influencing health outcomes. We evaluated the hypothesis that the respiratory virome is linked to systemic immune responses, using peripheral blood and nasopharyngeal swab samples from preschool-age children in the PreDicta cohort., Methods: Peripheral blood mononuclear cells from 51 children (32 asthmatics and 19 healthy controls) participating in the 2-year multinational PreDicta cohort were cultured with bacterial (Bacterial-DNA, LPS) or viral (R848, Poly:IC, RV) stimuli. Supernatants were analysed by Luminex for the presence of 22 relevant cytokines. Virome composition was obtained using untargeted high throughput sequencing of nasopharyngeal samples. The metagenomic data were used for the characterization of virome profiles and the presence of key viral families (Picornaviridae, Anelloviridae, Siphoviridae). These were correlated to cytokine secretion patterns, identified through hierarchical clustering and principal component analysis., Results: High spontaneous cytokine release was associated with increased presence of Prokaryotic virome profiles and reduced presence of Eukaryotic and Anellovirus profiles. Antibacterial responses did not correlate with specific viral families or virome profile; however, low antiviral responders had more Prokaryotic and less Eukaryotic virome profiles. Anelloviruses and Anellovirus-dominated profiles were equally distributed among immune response clusters. The presence of Picornaviridae and Siphoviridae was associated with low interferon-λ responses. Asthma or allergy did not modify these correlations., Conclusion: Antiviral cytokine responses at a systemic level reflect the upper airway virome composition. Individuals with low innate interferon responses have higher abundance of Picornaviruses (mostly Rhinoviruses) and bacteriophages. Bacteriophages, particularly Siphoviridae, appear to be sensitive sensors of host antimicrobial capacity, while Anelloviruses are not correlated with TLR-induced immune responses., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
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- 2023
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8. Physical activity in asthma control and its immune modulatory effect in asthmatic preschoolers.
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Maurer DJ, Liu C, Xepapadaki P, Stanic B, Bachert C, Finotto S, Gao YD, Graser A, Jartti T, Kistler W, Kowalski M, Lukkarinen H, Pasioti M, Tan G, Villiger M, Zhang L, Zhang N, Akdis M, Papadopoulos NG, and Akdis CA
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- Child, Cytokines metabolism, Exercise, Humans, Immunity, Asthma, Leukocytes, Mononuclear metabolism
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Background: The impact of physical activity on immune response is a hot topic in exercise immunology, but studies involving asthmatic children are scarce. Our aims were to examine whether there were any differences in the level of physical activity and daily TV attendance, to assess its role on asthma control and immune responses to various immune stimulants., Methods: Weekly physical activity and daily television attendance were obtained from questionnaires at inclusion of the PreDicta study. PBMC cultures were stimulated with phytohemagglutinin (PHA), R848, poly I:C, and zymosan. A panel of cytokines was measured and quantified in cell culture supernatants using luminometric multiplex immunofluorescence beads-based assay., Results: Asthmatic preschoolers showed significantly more TV attendance than their healthy peers (58.6% vs. 41.5% 1-3 h daily and only 25.7% vs. 47.2% ≤1 h daily) and poor asthma control was associated with less frequent physical activity (PA) (75% no or occasional activity in uncontrolled vs. 20% in controlled asthma; 25% ≥3 times weekly vs. 62%). Asthmatics with increased PA exhibited elevated cytokine levels in response to polyclonal stimulants, suggesting a readiness of circulating immune cells for type 1, 2, and 17 cytokine release compared to subjects with low PA and high TV attendance. This may also represent a proinflammatory state in high PA asthmatic children. Low physical activity and high TV attendance were associated with a decrease in proinflammatory cytokines. Proinflammatory cytokines were correlating with each other in in vitro immune responses of asthmatic children, but not healthy controls, this correlation was more pronounced in children with sedentary behavior., Conclusion: Asthmatic children show more sedentary behavior than healthy subjects, while poor asthma control is associated with a substantial decrease in physical activity. Our results suggest that asthmatic children may profit from regular exercise, as elevated cytokine levels in stimulated conditions indicate an immune system prepared for responding strongly in case of different types of infections. However, it has to be considered that a hyperinflammatory state in high PA may not be beneficial in asthmatic children., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
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- 2022
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9. Direct-acting antivirals in hepatitis C virus-positive mantle cell lymphomas.
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Merli M, Marino D, Cencini E, Rattotti S, Fraenza C, Grossi P, Bianchi B, Mora B, Sciarra R, Finotto S, Mecacci B, Passamonti F, Visco C, and Arcaini L
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- Aged, Aged, 80 and over, Female, Follow-Up Studies, Hepatitis C drug therapy, Hepatitis C virology, Humans, Italy epidemiology, Lymphoma, Mantle-Cell epidemiology, Lymphoma, Mantle-Cell virology, Male, Middle Aged, Prognosis, Retrospective Studies, Antiviral Agents therapeutic use, Hepacivirus drug effects, Hepatitis C complications, Lymphoma, Mantle-Cell drug therapy
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- 2021
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10. Clinical correlates of rhinovirus infection in preschool asthma.
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Jartti T, Liimatainen U, Xepapadaki P, Vahlberg T, Bachert C, Finotto S, Kowalski ML, Sobanska A, Lukkarinen H, Pasioti M, Vuorinen T, Zhang N, Zimmermann T, and Papadopoulos NG
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- Child, Child, Preschool, Cohort Studies, Disease Progression, Humans, Asthma epidemiology, Rhinovirus
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Background: Investigation of preschool asthma is important since not all children outgrow their illness during this age. Data are scarce on the role of rhinovirus (RV) infections in this patient group., Objectives: To investigate the role of RV infections in preschool asthma: (i) susceptibility factors, (ii) clinical course, and (iii) medium-term outcome., Methods: A total of 130 asthmatic children aged 4-6 years from the multinational PreDicta cohort were prospectively followed for a 12-month period. Allergy tests and a standard health questionnaire were carried out at study entry. Respiratory virus presence in nasopharyngeal washes was studied at illness visits and at 3 scheduled visits., Results: At study entry, mean age of the children was 5.3 years. Of 571 visits, 54% were positive for any virus and 39% for RV. Patient characteristics were only assessed with RV infection due to low number of other viruses. The use of supplementary vitamin D was inversely associated with RV infection (P < .05). RV infection was associated with more severe course of acute illness in terms of more severe nighttime coughing, more sleep disturbances, and more days with runny nose (all P < .05). RV infection was also associated with more severe disease course during the 12-month follow-up in terms of more nights with awakenings and more days of exercise-related symptoms (both P < .05)., Conclusions: Vitamin D supplementation may have an anti-rhinovirus effect. Both short- and medium-term outcomes suggest RV infection to be an important clinical marker of instable preschool asthma., (© 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
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- 2021
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11. B-cell receptor configuration and mutational analysis of patients with chronic lymphocytic leukaemia and trisomy 12 reveal recurrent molecular abnormalities.
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Falisi E, Novella E, Visco C, Guercini N, Maura F, Giaretta I, Pomponi F, Nichele I, Finotto S, Montaldi A, Neri A, and Rodeghiero F
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- Aged, Amino Acid Sequence, Animals, Cell Cycle Proteins genetics, Cell Transformation, Neoplastic genetics, Clone Cells pathology, Conserved Sequence, DNA Mutational Analysis, Disease Progression, F-Box Proteins genetics, F-Box-WD Repeat-Containing Protein 7, Female, Gene Rearrangement, B-Lymphocyte, Heavy Chain, Genes, Immunoglobulin, Genes, p53, Humans, In Situ Hybridization, Fluorescence, Interphase genetics, Male, Middle Aged, Molecular Sequence Data, Neoplastic Stem Cells pathology, Receptor, Notch1 genetics, Sequence Alignment, Sequence Homology, Amino Acid, Species Specificity, Syndrome, Ubiquitin-Protein Ligases genetics, Chromosomes, Human, Pair 12, DNA, Neoplasm genetics, Gene Rearrangement, B-Lymphocyte, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Mutation, Trisomy
- Abstract
Trisomy 12 (+12) is the third most frequent cytogenetic aberration in chronic lymphocytic leukaemia (CLL) retrievable both as the sole chromosomal abnormality or in association with additional alterations. NOTCH1 mutations are known to be more prevalent among +12 patients, whereas mutations of FBXW7, a gene involved in NOTCH1 degradation, that lead to the constitutional activation of NOTCH1 have not been investigated in this setting. We analyzed a unicentric cohort of 44 +12 patients with CLL for mutations of TP53, NOTCH1 and FBXW7 genes, and we correlated them with B-cell receptor (BCR) configurations. FBXW7, TP53 and NOTCH1 mutations were identified in 4.5%, 6.8% and 18.2% of patients, respectively. FBXW7 and NOTCH1 mutations appeared in a mutually exclusive fashion, suggesting that both aberrations might affect the same biological pathway. We found that 44.1% of +12 CLL patients had stereotyped B-cell receptors, which is significantly higher than that observed in patients with CLL and no +12 (27%, p = 0.01). Subsets #1, #8, #10, #28 and #59 were the most represented stereotyped patterns, and IGHV4-39*01 was the gene configuration most commonly used. There was a significantly higher risk for Richter's syndrome (RS) transformation in patients with NOTCH1 or FBXW7 mutations, with four of the seven (57%) patients developing RS and characterized at least by one of the two abnormalities. These observations suggest that, similarly to the aberrations of NOTCH1, FBXW7 gene mutations may also result in cell proliferation and evasion from apoptosis in patients with +12 CLL. Together with the extremely high frequency of stereotyped BCRs and RS transformation, these abnormalities appear to cluster in these CLL patients with additional chromosome 12, suggesting a connection with the prognosis of the disease., (Copyright © 2013 John Wiley & Sons, Ltd.)
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- 2014
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12. Double productive immunoglobulin sequence rearrangements in patients with chronic lymphocytic leukemia.
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Visco C, Moretta F, Falisi E, Facco M, Maura F, Novella E, Nichele I, Finotto S, Giaretta I, Ave E, Perbellini O, Guercini N, Scupoli MT, Trentin L, Trimarco V, Neri A, Semenzato G, Rodeghiero F, Pizzolo G, and Ambrosetti A
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- ADP-ribosyl Cyclase 1 genetics, ADP-ribosyl Cyclase 1 immunology, Aged, Female, Gene Expression, Humans, Immunoglobulin Heavy Chains immunology, Immunoglobulin Variable Region immunology, Immunophenotyping, Leukemia, Lymphocytic, Chronic, B-Cell immunology, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Male, Membrane Glycoproteins genetics, Membrane Glycoproteins immunology, Middle Aged, Prospective Studies, Retrospective Studies, Survival Analysis, Genes, Immunoglobulin Heavy Chain, Immunoglobulin Heavy Chains genetics, Immunoglobulin Variable Region genetics, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Mutation, Registries
- Abstract
The immunoglobulin heavy chain variable (IGHV) gene mutational status represents a major prognostic marker in chronic lymphocytic leukemia (CLL). Usually, the prognostic implications of IGHV gene analysis can be reliably ascertained but, occasionally, double productive rearrangements have been detected. Clinical presentation and biological features of such cases are unknown. Sixty patients with morphologically and phenotypically monoclonal CLL but double productive IGHV rearrangements were retrospectively identified by mRNA analysis from three Hematology Institutions. Clinical and biological features and survival of these 60 patients were compared with a control group of patients with CLL and single IGHV rearrangement. A prospective registry was used to assess the epidemiology of double productive IGHV among incidental patients with CLL. Using standard criteria to define IGHV-mutated (M) or unmutated (U) cases, 39 of the 60 patients (65%) with double productive IGHV rearrangement had concordant status (23 MM, 16 UU), while 21 (35%) had discordant IGHV status. As compared with M patients, the MM ones had lower CD38 expression, more favorable cytogenetics and more indolent clinical behavior. Cases with UU had similar characteristics of U patients. Discordant cases presented with adverse prognostic features and had an aggressive clinical behavior requiring early treatment, similar to U patients. The prevalence of double IGHV was 3.1%. Patients with CLL with double concordant mutational status (MM or UU) have a clinical course similar to that of the corresponding single IGHV status, while those exhibiting discordant status represent a high risk population. This may help correct stratification within clinical trials., (Copyright © 2013 Wiley Periodicals, Inc.)
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- 2013
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13. The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high-risk patients with chronic lymphocytic leukemia.
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Visco C, Finotto S, Pomponi F, Sartori R, Laveder F, Trentin L, Paolini R, Di Bona E, Ruggeri M, and Rodeghiero F
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- Aged, Antibodies, Monoclonal, Murine-Derived administration & dosage, Bendamustine Hydrochloride, Cytarabine administration & dosage, Cytogenetic Analysis, Drug Administration Schedule, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Male, Middle Aged, Neoplasm Staging, Nitrogen Mustard Compounds administration & dosage, Pilot Projects, Recurrence, Risk, Rituximab, Sequence Deletion, Survival Analysis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chromosome Aberrations, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 17, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
- Abstract
Treatment of patients with B-cell chronic lymphocytic leukemia (CLL) relapsed/refractory (R/R) to conventional treatments is particularly challenging. The combination of bendamustine and cytarabine has demonstrated distinct and synergistic mechanisms of action in preclinical studies on cell lines and primary tumor cells of several B-cell lymphomas, including 17p deleted or TP53 mutated CLL. The efficacy of rituximab (375 mg/m(2) , Day 1), plus bendamustine (70 mg/m(2) , days 1-2), and cytarabine (800 mg/m(2) , Day 1-3; R-BAC), every 28 days for up to four courses, was evaluated in a pilot trial enrolling 13 patients with very selected high-risk R/R CLL. All patients (median age 60 years, range 53-74) had symptomatic Binet stage B or C active disease requiring treatment, were characterized by adverse cytogenetics (17p deletion, 11q deletion, or both), unmutated immunoglobulin heavy-chain variable region, and were heavily pretreated (1-5, median three previous lines). Overall, R-BAC was well tolerated with limited non-hematological toxicity. Major toxicities were transient Grade 3/4 neutropenia and thrombocytopenia in 84% and 85% of patients, respectively. Overall response rate (OR) was 84%, including complete and partial response in 38% and 46% of patients, respectively. Patients with 17p deletion had an OR of 78%. After a median follow-up of 17 months, median progression-free survival was 16 months while median overall survival (OS) was not reached (1-year OS: 75 ± 13%). R-BAC is an active regimen in R/R heavily pretreated high-risk patients with CLL, representing an option for the treatment of patients that are usually refractory to standard therapy., (Copyright © 2013 Wiley Periodicals, Inc.)
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- 2013
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14. IL-28A (IFN-λ2) modulates lung DC function to promote Th1 immune skewing and suppress allergic airway disease.
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Koltsida O, Hausding M, Stavropoulos A, Koch S, Tzelepis G, Ubel C, Kotenko SV, Sideras P, Lehr HA, Tepe M, Klucher KM, Doyle SE, Neurath MF, Finotto S, and Andreakos E
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- Animals, Asthma pathology, Asthma therapy, CD11c Antigen metabolism, Cytokines genetics, Down-Regulation, Lung cytology, Lung immunology, Mice, OX40 Ligand metabolism, Recombinant Proteins genetics, Recombinant Proteins metabolism, Recombinant Proteins pharmacology, Th1 Cells cytology, Th1 Cells metabolism, Th17 Cells immunology, Th17 Cells metabolism, Th2 Cells immunology, Th2 Cells metabolism, Asthma immunology, Cytokines metabolism, Dendritic Cells immunology, Th1 Cells immunology
- Abstract
IL-28 (IFN-λ) cytokines exhibit potent antiviral and antitumor function but their full spectrum of activities remains largely unknown. Recently, IL-28 cytokine family members were found to be profoundly down-regulated in allergic asthma. We now reveal a novel role of IL-28 cytokines in inducing type 1 immunity and protection from allergic airway disease. Treatment of wild-type mice with recombinant or adenovirally expressed IL-28A ameliorated allergic airway disease, suppressed Th2 and Th17 responses and induced IFN-γ. Moreover, abrogation of endogenous IL-28 cytokine function in IL-28Rα(-/-) mice exacerbated allergic airway inflammation by augmenting Th2 and Th17 responses, and IgE levels. Central to IL-28A immunoregulatory activity was its capacity to modulate lung CD11c(+) dendritic cell (DC) function to down-regulate OX40L, up-regulate IL-12p70 and promote Th1 differentiation. Consistently, IL-28A-mediated protection was absent in IFN-γ(-/-) mice or after IL-12 neutralization and could be adoptively transferred by IL-28A-treated CD11c(+) cells. These data demonstrate a critical role of IL-28 cytokines in controlling T cell responses in vivo through the modulation of lung CD11c(+) DC function in experimental allergic asthma., (Copyright © 2011 EMBO Molecular Medicine.)
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- 2011
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15. Analysis of the oxygen sensing pathway genes in familial chronic myeloproliferative neoplasms and identification of a novel EGLN1 germ-line mutation.
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Albiero E, Ruggeri M, Fortuna S, Bernardi M, Finotto S, Madeo D, and Rodeghiero F
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- Adult, Aged, Chronic Disease, Humans, Hypoxia-Inducible Factor-Proline Dioxygenases, Male, Polycythemia Vera genetics, Signal Transduction genetics, Germ-Line Mutation, Myeloproliferative Disorders genetics, Oxygen metabolism, Procollagen-Proline Dioxygenase genetics
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- 2011
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16. A subset of patients with recurrent spontaneous abortion is deficient in transforming growth factor beta-2-producing "suppressor cells" in uterine tissue near the placental attachment site.
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Lea RG, Underwood J, Flanders KC, Hirte H, Banwatt D, Finotto S, Ohno I, Daya S, Harley C, and Michel M
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- Cell-Free System, Cells, Cultured, Embryo Implantation immunology, Female, Humans, In Situ Hybridization, Pregnancy, Suppressor Factors, Immunologic biosynthesis, Suppressor Factors, Immunologic deficiency, T-Lymphocytes, Regulatory immunology, Transforming Growth Factor beta deficiency, Abortion, Habitual immunology, Decidua immunology, Decidua pathology, T-Lymphocytes, Regulatory metabolism, Transforming Growth Factor beta biosynthesis
- Abstract
Problem: To determine if patients with unexplained recurrent miscarriage have a deficiency of decidual immunosuppressor cells that produce transforming growth factor beta type 2, as has been found in mice with abortion due to rejection and/or trophoblast failure., Methods: Decidual biopsy specimens were taken as near to the placental attachment site as possible under ultrasound guidance from first trimester legal termination (control) patients with recurrent miscarriage and non-viable pregnancy, and from patients with sporadic missed abortion. The tissue was tested for TGF beta-2+ suppressor cells by in situ hybridization, immunohistochemistry, and analysis of supernatants., Results: TGF beta-2-related suppressor molecules similar but not identical to those identified in pregnant mice were released by decidual lymphoid cells. Fifty percent of 14 recurrent miscarriage patients showed a lack of suppressor cells and 59% were subnormal in comparison to 20 controls and 5 sporadic miscarriage patients, where 80-85% of the patients had detectable suppressor cells., Conclusions: Suppressor cell deficiency is compatible with a role for rejection and/or trophoblast failure in some patients with recurrent miscarriage. Presence of suppressor cells in most patients with missed abortion (4/5) is compatible with an alternative cause of fetal death, similar to findings reported in genetic fetal death mice.
- Published
- 1995
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