7 results on '"Valentina Petrangeli"'
Search Results
2. Data from Induction of Both CD8+ and CD4+ T-Cell–Mediated Responses in Colorectal Cancer Patients by Colon Antigen-1
- Author
-
Filippo Belardelli, Giorgio Parmiani, Marco Tartaglia, Vittorina Zagonel, Licia Rivoltini, Chiara Castelli, Maria P. Perrone, Flavio Arienti, Arabella Mazzocchi, Sofia Guida, Luca Laurenti, Valentina Petrangeli, Giuseppina D'Agostino, Domenico Corsi, Valentina Fodale, Veronica Di Cristanziano, and Cristina Maccalli
- Abstract
Purpose: Colon antigen-1 (COA-1) was recently identified as a novel antigen of colorectal cancer encoded by the UBXD5 gene. Here, we evaluated whether a specific T-cell-mediated response directed against this molecule can occur in colorectal cancer patients.Experimental Design: Antigen- and tumor-specific immunologic responses of peripheral blood mononuclear cells (PBMC) stimulated in vitro with the MHC class II-associated immunogenic epitope of COA-1 (FSTFPPTLYQDDTLTLQAAG) were analyzed by IFN-γ ELISPOT assay.Results: COA-1-specific and tumor-reactive T lymphocytes were isolated from all (n = 7) HLA-DRβ1*0402+ or *1301+ colorectal cancer patients with progressive disease (Dukes' C and D) but not in patients (n = 4) with early-stage tumor (Dukes' A and B) and in healthy donors (n = 5), suggesting that the immune response against this antigen is associated with the progression of colorectal cancer. COA-1- and tumor-specific T lymphocytes displayed a CD3+CD4+CD69+CD45RA+ phenotype, compatible with the activated effector-type T-cell subset, and most of them exerted cytotoxic activity against HLA-matched and COA-1+ tumor cells. COA-1-specific T cells could also be isolated by in vitro stimulation of peripheral blood mononuclear cells with autologous dendritic cells loaded with tumor lysate, suggesting that this antigen can generate a dominant immunologic response against colorectal cancer cells. Notably, we could identify also COA-1-derived epitopes binding to HLA-A*0201 molecules that elicited antigen- and tumor-specific CD8+ T-cell-mediated responses in colorectal cancer patients.Conclusions: Both CD4+ and CD8+ T-cell responses against COA-1 can occur in colorectal cancer patients with metastatic disease, suggesting that this antigen is suitable for immunotherapeutic protocols of these patients.
- Published
- 2023
3. Cognitive profile of disorders associated with dysregulation of the RAS/MAPK signaling cascade
- Author
-
Eugenio Mercuri, Isabella Vasta, Francesca Pantaleoni, Laura Cesarini, Marco Tartaglia, Paolo Mariotti, Daniela Ricci, Marta Cerutti, Angelo Selicorni, Stefano Vicari, Paolo Alfieri, Chiara Leoni, Valentina Petrangeli, and Giuseppe Zampino
- Subjects
Adult ,Male ,Proto-Oncogene Proteins B-raf ,MAPK/ERK pathway ,Adolescent ,MAP Kinase Signaling System ,Developmental Disabilities ,MAP Kinase Kinase 1 ,Protein Tyrosine Phosphatase, Non-Receptor Type 11 ,Biology ,Gene mutation ,medicine.disease_cause ,Proto-Oncogene Proteins p21(ras) ,Young Adult ,Costello syndrome ,Genetics ,medicine ,Humans ,HRAS ,Child ,Genetics (clinical) ,Mutation ,Infant ,Cognition ,medicine.disease ,Proto-Oncogene Proteins c-raf ,Phenotype ,Child, Preschool ,ras Proteins ,SOS1 ,Female ,KRAS ,Cognition Disorders ,SOS1 Protein - Abstract
Mutations in genes coding for transducers participating in the RAS/MAPK pathway have been identified as the molecular cause underlying a group of clinically related developmental disorders with cognitive deficits of variable severity. To determine the spectrum of cognitive defects associated with dysregulation of this signal cascade, we studied the profile of cognitive abilities in patients with mutations affecting the PTPN11, SOS1, HRAS, KRAS, BRAF, RAF1, and MEK1 genes and phenotype-genotype correlations. Our findings support the observation that heterogeneity in cognitive abilities can be at least partially ascribed to the individual affected genes and type of mutation involved. While mutations affecting transducers upstream of RAS were less frequently associated with mental retardation, mutations in downstream components of the pathway were generally associated with a more severe cognitive impairment. Among patients with a heterozygous PTPN11 mutation, the T468M substitution was associated with a mean IQ significantly higher compared to that of individuals carrying the N308D change. Our study provides insights on the range of cognitive abilities in patients with gene mutations causing dysregulation of RAS signaling suggesting that the presence and severity of cognitive involvement can be predicted in part by the gene involved.
- Published
- 2009
4. Germline BRAF Mutations in Noonan, LEOPARD, and Cardiofaciocutaneous Syndromes: Molecular Diversity and Associated Phenotypic Spectrum
- Author
-
Efisio Puxeddu, Giorgia Esposito, Angelo Selicorni, Cesare Rossi, Anna Sarkozy, Sonia Moretti, Maria Lisa Dentici, Marco Tartaglia, Grazia M.S. Mancini, Bruno Dallapiccola, Francesca Pantaleoni, Margherita Silengo, Viviana Cordeddu, Maria Cristina Digilio, Laura Mazzanti, Anna Paola Scioletti, Franco Stanzial, Luigi Memo, Bruno Marino, Giovanni Battista Ferrero, Francesca Faravelli, Claudio Carta, Giuseppe Zampino, Francesca Romana Lepri, Bruce D. Gelb, Valentina Petrangeli, Liborio Stuppia, Clinical Genetics, A. Sarkozy, C. Carta, S. Moretti, G. Zampino, M.C. Digilio, F. Pantaleoni, A.P. Scioletti, G. Esposito, V. Cordeddu, F. Lepri, V. Petrangeli, M.L. Dentici, G.M. Mancini, A. Selicorni, C. Rossi, L. Mazzanti, B. Marino, G:B. Ferrero, M.C. Silengo, L. Memo, F. Stanzial, F. Faravelli, L. Stuppia, E. Puxeddu, B.D. Gelb, B. Dallapiccola, and M. Tartaglia.
- Subjects
Heart Defects, Congenital ,Male ,Proto-Oncogene Proteins B-raf ,Genotype ,NOONAN, LEOPARD AND CARDIOFACIOCUTANEOUS SYNDROMES ,Mutation, Missense ,Biology ,RASopathy ,genotype-phenotype correlation ,Cardiofaciocutaneous syndrome ,LEOPARD Syndrome ,Article ,Germline ,Noonan syndrome ,Leopard syndrome ,BRAF ,Mutation ,Cohort Studies ,Germline mutation ,Gene Frequency ,SDG 3 - Good Health and Well-being ,Genetics ,medicine ,Humans ,Abnormalities, Multiple ,Germ-Line Mutation ,Genetics (clinical) ,mutation analysis ,braf ,cardiofaciocutaneous syndrome ,cfcs ,functional studies ,leopard syndrome ,noonan syndrome ,LEOPARD syndrome ,CFCS ,Genetic Variation ,medicine.disease ,PTPN11 ,Phenotype ,BRAF MUTATIONS ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,LEOPARD AND CARDIOFACIOCUTANEOUS SYNDROMES ,Face ,Skin Abnormalities ,NOONAN ,Female ,Noonan Syndrome with Multiple Lentigines - Abstract
Noonan, LEOPARD, and cardiofaciocutaneous Syndromes (NS, LS, and CFCS) are developmental disorders with overlapping features including distinctive facial dysmorphia, reduced growth, cardiac defects, skeletal and ectodermal anomalies, and variable cognitive deficits. Dysregulated RAS-mitogen-activated protein kinase (MAPK) signal traffic has been established to represent the molecular pathogenic cause underlying these conditions. To investigate the phenotypic spectrum and molecular diversity of germline mutations affecting BRAF, which encodes a serine/threonine kinase functioning as a RAS effector frequently mutated in CFCS, subjects with a diagnosis of NS (N = 270), LS (N = 6), and CFCS (N = 33), and no mutation in PTPN11, SOS1, KRAS, RAF1, MEK1, or MEK2, were screened for the entire coding sequence of the gene. Besides the expected high prevalence of mutations observed among CFCS patients (5296), a de novo heterozygous missense change was identified in one subject with LS (17%) and five individuals with NS (1.9%). Mutations mapped to multiple protein domains and largely did not overlap with cancer-associated defects. NS-causing mutations had not been documented in CFCS, suggesting that the phenotypes arising from germline BRAF defects might be allele specific. Selected mutant BRAF proteins promoted variable gain of function of the kinase, but appeared less activating compared to the recurrent cancer-associated p.Val600Glu mutant. Our findings provide evidence for a wide phenotypic diversity associated with mutations affecting BRAF, and occurrence of a clinical continuum associated with these molecular lesions. Hum Mutat 30, 695-702, 2009. (C) 2009 Wiley-Liss, Inc.
- Published
- 2009
5. Somatically acquired JAK1 mutations in adult acute lymphoblastic leukemia
- Author
-
Stefan N. Constantinescu, Andrea Camera, Robin Foà, Marco Tartaglia, Hélène Cavé, Laurent Knoops, Simone Martinelli, Lorenzo Stella, Francesca Paoloni, Valentina Petrangeli, Valentina Fodale, Simona Tavolaro, Angela Battistini, Cristina Ariola, Giovanni Cazzaniga, Emmanuelle Clappier, Alessandra Fragale, Sabina Chiaretti, Marco Vignetti, Andrea Biondi, Jean-Christophe Renauld, Assunta Tornesello, Bruce D. Gelb, Giovanni Pizzolo, Massimo Sanchez, Monica Messina, Tekla Hornakova, Elisabetta Flex, Flex, E, Petrangeli, V, Stella, L, Chiaretti, S, Hornakova, T, Knoops, L, Ariola, C, Fodale, V, Clappier, E, Paoloni, F, Martinelli, S, Fragale, A, Sanchez, M, Tavolaro, S, Messina, M, Cazzaniga, G, Camera, A, Pizzolo, G, Tornesello, A, Vignetti, M, Battistini, A, Cavé, H, Gelb, B, Renauld, J, Biondi, A, Constantinescu, S, Foà, R, Tartaglia, M, UCL - Cliniques universitaires Saint-Luc, and UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique
- Subjects
Models, Molecular ,Somatic cell ,DNA Mutational Analysis ,animal cell ,medicine.disease_cause ,T cell lymphoma ,Mice ,Mutant Protein ,Models ,JAK1 ,ALL ,MUTATIONS ,T lymphocyte ,Immunology and Allergy ,gene mutation ,Settore CHIM/02 - Chimica Fisica ,Leukemic ,child ,Mutation ,Tumor ,Janus kinase 1 ,Gene Expression Regulation, Leukemic ,Kinase ,adult ,allele ,apoptosis ,article ,protein domain ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,enzyme activity ,medicine.anatomical_structure ,leukemia cell ,priority journal ,Signal transduction ,signal transduction ,mutational analysis ,lymphoma cell ,alleles ,animals ,base sequence ,cell line ,dna mutational analysis ,enzymology/genetics/pathology ,gene expression profiling ,gene expression regulation ,genetics ,humans ,janus kinase 1 ,leukemic ,metabolism ,mice ,models ,molecular ,molecular sequence data ,mutant proteins ,mutation ,precursor cell lymphoblastic leukemia-lymphoma ,tumor ,T cell ,prevalence ,Molecular Sequence Data ,Immunology ,dexamethasone ,acute lymphoblastic leukemia ,protein localization ,Biology ,leukemogenesis ,interleukin 3 ,Cell Line ,Cell Line, Tumor ,Acute lymphocytic leukemia ,medicine ,Animals ,Humans ,controlled study ,human ,mouse ,Alleles ,nonhuman ,Base Sequence ,Animal ,gene interaction ,missense mutation ,Gene Expression Profiling ,genetic transcription ,Brief Definitive Report ,treatment response ,Molecular ,Janus Kinase 1 ,medicine.disease ,Molecular biology ,cyclosporin A ,gene function ,Gene Expression Regulation ,interleukin 9 ,adolescent ,gene expression ,Adult Acute Lymphoblastic Leukemia ,Brief Definitive Reports ,Mutant Proteins ,prognosis ,molecular model ,upregulation - Abstract
Aberrant signal transduction contributes substantially to leukemogenesis. The Janus kinase 1 (JAK1) gene encodes a cytoplasmic tyrosine kinase that noncovalently associates with a variety of cytokine receptors and plays a nonredundant role in lymphoid cell precursor proliferation, survival, and differentiation. We report that somatic mutations in JAK1 occur in individuals with acute lymphoblastic leukemia (ALL). JAK1 mutations were more prevalent among adult subjects with the T cell precursor ALL, where they accounted for 18% of cases, and were associated with advanced age at diagnosis, poor response to therapy, and overall prognosis. All mutations were missense, and some were predicted to destabilize interdomain interactions controlling the activity of the kinase. Three mutations that were studied promoted JAK1 gain of function and conferred interleukin (IL)-3–independent growth in Ba/F3 cells and/or IL-9–independent resistance to dexamethasone-induced apoptosis in T cell lymphoma BW5147 cells. Such effects were associated with variably enhanced activation of multiple downstream signaling pathways. Leukemic cells with mutated JAK1 alleles shared a gene expression signature characterized by transcriptional up-regulation of genes positively controlled by JAK signaling. Our findings implicate dysregulated JAK1 function in ALL, particularly of T cell origin, and point to this kinase as a target for the development of novel antileukemic drugs.
- Published
- 2008
6. Somatic PTPN11 mutations in childhood acute myeloid leukaemia
- Author
-
Ivano Iavarone, Giovanni Cazzaniga, Valentina Petrangeli, Claudio Carta, Riccardo Masetti, Andrea Pession, Mariella Sorcini, Andrea Biondi, Simone Martinelli, Giuseppe Basso, Maurizio Aricò, Monica Spinelli, Emanuela Giarin, Marco Tartaglia, Franco Locatelli, Tartaglia M, Martinelli S, Iavarone I, Cazzaniga G, Spinelli M, Giarin E, Petrangeli V, Carta C, Masetti R, Aricò M, Locatelli F, Basso G, Sorcini M, Pession A, Biondi A., Tartaglia, M, Martinelli, S, Iavarone, I, Cazzaniga, G, Spinelli, M, Giarin, E, Petrangeli, V, Carta, C, Masetti, R, Arico, M, Locatelli, F, Basso, G, Sorcini, M, Pession, A, and Biondi, A
- Subjects
Male ,musculoskeletal diseases ,Neuroblastoma RAS viral oncogene homolog ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,FAB-M5 subtype ,Adolescent ,CHILDHOOD ,Protein Tyrosine Phosphatase, Non-Receptor Type 11 ,PTPN11 ,medicine.disease_cause ,Proto-Oncogene Proteins p21(ras) ,Leukocyte Count ,Germline mutation ,childhood acute myeloid leukaemia ,Proto-Oncogene Proteins ,Internal medicine ,medicine ,Humans ,somatic mutation ,Child ,Mutation ,Hematology ,business.industry ,Intracellular Signaling Peptides and Proteins ,Infant ,Receptor Protein-Tyrosine Kinases ,medicine.disease ,Neoplasm Proteins ,Leukemia ,Genes, ras ,fms-Like Tyrosine Kinase 3 ,Leukemia, Myeloid ,Child, Preschool ,SHP-2 ,Acute Disease ,Leukemia, Monocytic, Acute ,Immunology ,Fms-Like Tyrosine Kinase 3 ,ras Proteins ,Female ,Protein Tyrosine Phosphatases ,business ,LEUKEMIA ,French–American–British classification - Abstract
Somatic mutations in PTPN11, the gene encoding the transducer SHP-2, have emerged as a novel class of lesions that upregulate RAS signalling and contribute to leukaemogenesis. In a recent study of 69 children and adolescents with de novo acute myeloid leukaemia (AML), we documented a non-random distribution of PTPN11 mutations among French - American British (FAB) subtypes. Lesions were restricted to FAB-M5 cases, where they were relatively common ( four of 12 cases). Here, we report on the results of a molecular screening performed on 181 additional unselected patients, enrolled in participating institutions of the Associazione Italiana Ematologia Oncologia Pediatrica - AML Study Group, to provide a more accurate picture of the prevalence, spectrum and distribution of PTPN11 mutations in childhood AML and to investigate their clinical relevance. We concluded that PTPN11 defects do not represent a frequent event in this heterogeneous group of malignancies ( 4 center dot 4%), although they recur in a considerable percentage of patients with FAB-M5 ( 18%). PTPN11 lesions rarely occur in other subtypes. Within the FAB- M5 group no clear association of PTPN11 mutations with any clinical variable was evident. Nearly two third of the patients with this subtype were found to harbour an activating mutation in PTPN11, NRAS, KRAS2 or FLT3.
- Published
- 2005
7. Induction of both CD8+ and CD4+ T-cell-mediated responses in colorectal cancer patients by colon antigen-1
- Author
-
Giuseppina D'Agostino, Vittorina Zagonel, Valentina Fodale, Cristina Maccalli, Filippo Belardelli, Sofia Guida, Flavio Arienti, Marco Tartaglia, Valentina Petrangeli, Maria Paola Perrone, Chiara Castelli, Giorgio Parmiani, Veronica Di Cristanziano, Luca Laurenti, Arabella Mazzocchi, Domenico Corsi, and Licia Rivoltini
- Subjects
CD4-Positive T-Lymphocytes ,Cancer Research ,T cell ,CD8-Positive T-Lymphocytes ,Lymphocyte Activation ,Epitope ,Interferon-gamma ,Antigen ,Antigens, Neoplasm ,HLA-A2 Antigen ,medicine ,Cytotoxic T cell ,Humans ,Antigen Presentation ,HLA-A Antigens ,business.industry ,ELISPOT ,Cancer ,medicine.disease ,medicine.anatomical_structure ,Oncology ,Immunology ,business ,Colorectal Neoplasms ,CD8 - Abstract
Purpose: Colon antigen-1 (COA-1) was recently identified as a novel antigen of colorectal cancer encoded by the UBXD5 gene. Here, we evaluated whether a specific T-cell-mediated response directed against this molecule can occur in colorectal cancer patients. Experimental Design: Antigen- and tumor-specific immunologic responses of peripheral blood mononuclear cells (PBMC) stimulated in vitro with the MHC class II-associated immunogenic epitope of COA-1 (FSTFPPTLYQDDTLTLQAAG) were analyzed by IFN-γ ELISPOT assay. Results: COA-1-specific and tumor-reactive T lymphocytes were isolated from all (n = 7) HLA-DRβ1*0402+ or *1301+ colorectal cancer patients with progressive disease (Dukes' C and D) but not in patients (n = 4) with early-stage tumor (Dukes' A and B) and in healthy donors (n = 5), suggesting that the immune response against this antigen is associated with the progression of colorectal cancer. COA-1- and tumor-specific T lymphocytes displayed a CD3+CD4+CD69+CD45RA+ phenotype, compatible with the activated effector-type T-cell subset, and most of them exerted cytotoxic activity against HLA-matched and COA-1+ tumor cells. COA-1-specific T cells could also be isolated by in vitro stimulation of peripheral blood mononuclear cells with autologous dendritic cells loaded with tumor lysate, suggesting that this antigen can generate a dominant immunologic response against colorectal cancer cells. Notably, we could identify also COA-1-derived epitopes binding to HLA-A*0201 molecules that elicited antigen- and tumor-specific CD8+ T-cell-mediated responses in colorectal cancer patients. Conclusions: Both CD4+ and CD8+ T-cell responses against COA-1 can occur in colorectal cancer patients with metastatic disease, suggesting that this antigen is suitable for immunotherapeutic protocols of these patients.
- Published
- 2008
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.