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  • 1
    Publication Date: 1996-05-01
    Description: Chronic myelogenous leukemia (CML) cells are characterized by a t(9;22) translocation, which can encode one of two chimeric P210 bcr-abl fusion proteins, comprising products of either the b2a2 or the b3a2 exon junction. The junctional sequences represent potentially immunogenic tumor-specific antigens. Despite their intracellular location, the fusion proteins might be recognized immunologically by T lymphocytes if peptides, derived from these unique sequences, are capable of presentation by the major histocompatibility complex molecules. We previously found that four peptides, 9 to 11 amino acids long, spanning the b3a2 CML breakpoint bind with high or intermediate affinity to purified HLA class I molecules A3, A11, B8, or both A3 and A11. We tested the ability of these peptides to elicit specific class I restricted cytotoxic T lymphocytes (CTLs) in vitro in HLA-matched healthy donors. In addition, a longer b3a2 CML-breakpoint-derived peptide, 25 aminoacids in length (b3a2–25), was studied for its ability to induce peptide-specific, class II-mediated, T-cell proliferation. In four of four HLA-A3 donors tested, CML-A3/A11-peptide specific CTLs were induced that killed an allogeneic HLA-A3-matched peptide pulsed leukemia cell line. In two of three HLA-A3 donors, the CML-A3/A11 peptide was able to induce killing of autologous and allogeneic HLA- matched peptide-pulsed peripheral blood mononuclear cells (PBMC). CML- A3 peptide induced peptide specific CTLs in one of the four HLA A3 donors tested. No killing was observed in two HLA-B8 and two HLA-A11 donors. PBMC from seven donors were also tested for anti b3a2–25 peptide proliferation in a thymidine incorporation assay. Specific proliferation was detected in three donors, all of the HLA-DR11 haplotype. These data represent the first evidence of a cytolytic human immune response against CML bcr-abl oncogene-derived peptides and provide a rationale for developing peptide-based vaccines for this disease.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 2
    Publication Date: 1995-05-15
    Description: Many human leukemias are characterized by chromosomal translocations yielding hybrid RNAs capable of encoding fusion chimeric proteins. The unique amino acid sequences found in these oncogenic fusion proteins represent true tumor-specific antigens that are potentially immunogenic. Although these leukemia-specific fusion proteins have an intracellular location, they might be recognized immunologically by T lymphocytes if peptides derived from the unique sequences are capable of presentation by the major histocompatibility complex (MHC) molecules on leukemic cells. The ability of a series of synthetic peptides corresponding to the junctional sequences of chronic myelogenous leukemia (CML)-derived bcr-abl and acute promyelocytic leukemia (APL)-derived PML-RAR alpha fusion proteins to bind to purified class I molecules was studied. A series of 152 peptides 8, 9, 10, and 11 amino acids in length, spanning the b3a2 and b2a2 breakpoints for CML and PML-RAR alpha A and B breakpoints for APL were analyzed for HLA A1, A2.1, A3.2, A11, A24, B7, B8, and B27 binding motifs. Twenty-one CML peptides and 4 APL peptides were predicted to be potential HLA class I binders. The peptides were tested for binding to appropriate purified HLA molecules in a competition radioimmunoassay. Four peptides derived from b3a2 CML breakpoint bound with high (〈 50 nmol/L) or intermediate (〈 or = 500 nmol/L) affinity to HLA A3, A11, and B8. None of the CML b2a2 or PML-RAR alpha A or B junctional peptides showed affinity of this magnitude for the HLA class I molecules tested. This is the first evidence that tumor-specific breakpoint peptides can bind human MHC class I molecules and provides a rationale for developing a therapeutic vaccine strategy.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 3
    Publication Date: 2000-03-01
    Description: Chronic myelogenous leukemia (CML) presents a unique opportunity to develop therapeutic strategies using vaccination against a truly tumor-specific antigen that is also the oncogenic protein required for neoplasia. CML is characterized by the t(9;22) that results in the bcr-abl fusion oncogene and in the expression of a chimeric protein product p210. Previously we have shown that peptides derived from amino acid sequences crossing the b3a2 fusion breakpoint in p210 elicit class I restricted cytotoxic T lymphocytes and class II responses, respectively, in vitro. Such sequences may thus comprise absolutely tumor-specific antigens in a peptide-based vaccine. We evaluated the safety and immunogenicity of a multidose, bcr-abl breakpoint peptide vaccine in 12 adults with chronic-phase CML. Cohorts of 3 patients each received either 50 μg, 150 μg, 500 μg, or 1500 μg total peptide mixed with 100 μg QS-21 as an immunological adjuvant. Delayed-type hypersensitivity (DTH), humoral responses, and unprimed ex vivo autologous proliferation (3H-thymidine incorporation) and cytotoxicity (chromium-51 release) responses were measured. All 68 vaccinations were well tolerated without significant adverse effects. In 3 of the 6 patients treated at the 2 highest dose levels of vaccine, peptide-specific, T-cell proliferative responses (n = 3) and/or DTH responses (n = 2) were generated that lasted up to 5 months after vaccination. Cytotoxic T lymphocytes have not been identified. In conclusion, a tumor-specific, bcr-abl derived peptide vaccine can be safely administered to patients with chronic-phase CML and can elicit a bcr-abl peptide-specific immune response despite the presence of active disease in these patients and approximately 1012 leukemia cells.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 4
    Publication Date: 2005-11-16
    Description: Immunoglobulin (Ig) gene analysis delineates critical features of the clonal history of a B-cell tumor. After antigen interaction, mature B-cells undergo somatic mutation of the V-genes and isotype switch recombination, generally in the germinal center (GC). Receptor revision by secondary recombination of the V-genes with re-expression of recombination activating gene (RAG) enzymes rarely occurs at this stage. From a small series, we have reported that most hairy cell leukemias (HCL) carry mutated VH genes, with low levels of intraclonal heterogeneity, while a minor subset have unmutated VH genes. Both subsets commonly have ongoing Ig isotype switch events and express activation induced cytidine deaminase (AID). However HCL lack the GC markers CD27 and CD38, and CD23, a chemokine essential for lymph node entry. In order to probe more fully the differentiation status of the cell of origin, both VH and VL tumor-derived genes were evaluated in an expanded series of 38 HCL. From analysis of VH, the VH3 family usage was most common (24/38, 63%), with significant preference of the VH3-30 member in 10/38 cases (26%, p=0,00001), and JH4b segment utilised in 50% of cases. Most HCL (35/38) carried variable tiers of mutations (87–98.6% homology to germline), with low level of intraclonal heterogeneity also in cases with
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 5
    Publication Date: 2017-04-04
    Description: On October 25th 2011 a devastating flood hit the Vara and Magra valleys in Italy and left an unforgettable scratch in the inhabitants’ minds. Cloudy with a Chance of ideas! (Piovono idee!) is an active journey of discovery and training on hydrogeological risk and climate change. Land preservation and safety of people living on it are issues, which we would like to help citizens get perception about, in order to instill awareness on the actions that can be taken towards risk mitigation. Cloudy with a Chance of ideas! stemmed from this belief, and it is the result of a collaborative planning in which primary and secondary school students, living within cities heavily hit by the flood, took actively part. Children were helped by experts and scientists to build an exhibition devoted to hydrogeological risk. Here interactive workspaces, games and educational laboratories, allow visitors explore concepts, phenomena and their consequences on land and inhabitants. Issues are addressed from a daily actions perspective, where everybody might make the difference towards sustainability and trigger good practices on natural hazards risk reduction.
    Description: Published
    Description: 121-124
    Description: 4A. Clima e Oceani
    Description: restricted
    Keywords: hydrogeological risk, climate change, prevention, environmental impact, territory. ; 01. Atmosphere::01.01. Atmosphere::01.01.02. Climate
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: book chapter
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  • 6
    Publication Date: 2017-04-04
    Description: L’alluvione del 25 ottobre 2011 ha violentemente colpito diversi comuni dello Spezzino e della Lunigiana in seguito ad una forte precipitazione che in sei ore ha riversato 542 mm di pioggia causando la piena dei fiumi Vara e Magra e dei torrenti affluenti nelle zone colpite con inondazione di diverse entità in tutta la Val di Vara e la Val di Magra. “Piovono idee!” è un percorso attivo di scoperta di educazione al rischio idrogeologico e di riflessione sui cambiamenti climatici che parte dai ragazzi allo scopo di educarli al rispetto della natura e del loro territorio. Cosa si sente durante un’alluvione? Perché avviene? E, soprattutto, cosa possiamo fare noi per evitare che accada di nuovo? Destinato anzitutto alle scuole del secondo ciclo della scuola primaria ed alle scuole secondarie di primo grado, Piovono idee! coinvolge i ragazzi facendoli collaborare alla costruzione degli exhibit e dei modelli e giochi scientifici di modo che possano proporre alla cittadinanza di condividere un percorso che dà voce all’evento che hanno vissuto per confrontare con gli altri le proprie paure e i propri pensieri sull’alluvione che ha colpito il loro territorio. I temi di Piovono idee! sono il rischio idrogeologico ed i cambiamenti climatici trattati insieme a 378 ragazzi dagli 8 ai 14 anni di 32 classi delle 15 scuole primarie e secondarie di primo grado di BORGHETTO VARA, BRUGNATO, MONTEROSSO, VERNAZZA, RIOMAGGIORE, PIGNONE, RICCO’ DEL GOLFO, AULLA e RAGNAIA (AULLA), i comuni maggiormente colpiti dall’alluvione del 25 ottobre 2011, e da un campione di 6 classi di scuola media secondaria di primo grado di LA SPEZIA dell’ISA 1, 3 e 6 (rispettivamente S.M. “V. Alfieri”, “U. Mazzini” e “J.Piaget”). Piovono idee! si articola in più fasi: laboratori di progettazione partecipata con le scuole (raccolta di materiali e costruzione degli exhibit con le classi), allestimento e visite guidate alla mostra. I ragazzi che hanno avuto modo di rappresentare la loro esperienza costruendo un pezzetto di mostra, sono stati orgogliosi di riconoscere il loro contributo durante la visita. Piovono idee! è il risultato di una ricerca di modello didattico-comunicativo stimolante che coinvolga emotivamente il fruitore del percorso attivo che dovrebbe tornare a casa divertito ma anche consapevole di aver riflettuto su quanto i suoi comportamenti quotidiani possano influire sul bene comune e abbiano quindi un impatto sulla società. Questo percorso di conoscenza di cos’è il rischio idrogeologico e come si può affrontare e di approfondimento dei temi dell’inquinamento e di quanto possa pesare sui cambiamenti climatici viene proposto alla cittadinanza dando voce a vissuti, riflessioni e soluzioni dei ragazzi e potrà essere nuovamente allestito, aggiornato ed arricchito in futuro. Perché Piovono idee! è il luogo dove provare a cercare risposte a fenomeni che, seppure imprevedibili ed incontrollabili, possono risultare meno devastanti e spaventosi se compresi ed affrontati correttamente.
    Description: Unpublished
    Description: Palazzo dei Congressi, Pisa
    Description: 6A. Monitoraggio ambientale, sicurezza e territorio
    Description: restricted
    Keywords: educazione al rischio idrogeologico, conoscenza, prevenzione ; 05. General::05.08. Risk::05.08.99. General or miscellaneous
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: Conference paper
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  • 7
    Publication Date: 2017-04-04
    Description: It is increasingly acknowledged that disasters are the result of natural and social processes (Okazaki, 2007). Unlike the natural conditions that have a strong unpredictability component, social dimension of the disaster risk relates to the way human being interacts with natures. Hence, human behavior is the crucial factor in the degree of vulnerability and the likelihood of disasters taking place. Often people seem to know that a natural disaster might hit them, nonetheless the lack of awareness results in a general underestimation for effectiveness of actions towards risk mitigation. In many countries only few households or public buildings have disaster plans and supply kits, or have retrofitted and safe-proofed the inside, in case of earthquakes. Similarly little actions have been taken to safe-proof land in case of hydrogeologic threat. Disaster preparedness and prevention programs often remain in the domain of assumptions instead of evidence (Horton, 2011). Since disasters are infrequent in nature and memories are short (Komac, 2009; Biernacki et al., 2008; Wisner, 2006; Komac et al., 2011), there is an urge to promote culture of prevention and preparedness. The misconception about disasters as nature’s curse has most to do with mindset of people towards safety culture and the chance to live hazard in a sustainable way. The future emergency response needs to be better aligned with a longer term perspective in terms of development, crucial socioeconomic investments and infrastructure and, above all, preparedness (Horton, 2011). Here, education plays a significant role. The key to reduce risk is to start from scratch. We need to enhance capacity building for disaster risk reduction and, to do so, we need to educate both decision makers and general public. The Hyogo Framework for Action 2005-2015 Building the Resilience of Nations and Communities to Disasters, adopted at the World Conference on Disaster Reduction, highlights knowledge and education as one of the five main priorities of action. In this paper we deal with actions based on education to challenge perception and memory of disasters while builing knowledge and skills essential for disaster preparedness. Having children has a chief target one can rely on a chain reaction (domino effect): children transmit the risk-related knowledge to their parents and other people in their social network (e.g.: Cardona, 2007; Stoltman et al., 2007; Wisner, 2006; Kuhlicke et al., 2011).Living in a natural hazard prone land requires a multi-spectrum, coordinated and synergic approach to risk reduction including on one end the improvement scientific knowledge on natural phenomena and vulnerability, on the other end actions on emergency plans. However, all actions are less effective without a culture of prevention and preparedness. This can be achieved only through education, starting from the youngest and through a permanent training process. Interdisciplinary issue for more effective disaster resilience enabling cooperation at all levels and the high level of motivation and transparency among the team members coming directly from risk management organizations is our strengths and we support the transferability of our project to other Provinces and Regions encouraging a collaborative risk management to knowledge sharing of natural risk.
    Description: Published
    Description: Palazzo dei Congressi, Stazione Marittima, Trieste
    Description: 6A. Monitoraggio ambientale, sicurezza e territorio
    Description: restricted
    Keywords: risk mitigation, active learning experience, preparedness ; 05. General::05.08. Risk::05.08.99. General or miscellaneous
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: Conference paper
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  • 8
    Publication Date: 2017-04-04
    Description: The ERiNat project Educazione ai Rischi Naturali (Training on Natural Risks) offers training on environmental safety within the context of Life Long Learning through a permanent training process aimed at providing the population with a basic education (knowledge, awareness, how to act, self-protection and prevention) on natural risks and at creating a cultural milieu which ensures a turn-over of citizens that choose to take part in the voluntary world.
    Description: Published
    Description: Fiera district, terza torre - Bologna
    Description: 6A. Monitoraggio ambientale, sicurezza e territorio
    Description: restricted
    Keywords: natural risks, knowledge, how to act, self-protection, prevention, earthquakes, landslides, floods, forest fire, safety ; 05. General::05.08. Risk::05.08.99. General or miscellaneous
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: Poster session
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