0000000000065165

AUTHOR

Giorgio Inghirami

showing 7 related works from this author

Platelet-derived growth factor alpha mediates the proliferation of peripheral T-cell lymphoma cells via an autocrine regulatory pathway.

2014

Peripheral T-cell lymphomas not otherwise specified (PTCL/NOS) are very aggressive tumors characterized by consistent aberrant expression of platelet-derived growth factor receptor alpha (PDGFRA). In this study, we aimed to identify the determinants of PDGFRA activity in PTCL/NOS and to elucidate the biological consequences of its activation. We observed overexpression of the PDGFRA gene by gene expression profiling in most of the tested PTCLs and confirmed the expression of PDGFRA and phospho-PDGFRA using immunohistochemistry. The integrity of the PDFGRA locus was demonstrated using several different approaches, including massive parallel sequencing and Sanger sequencing. PDGF-AA was found…

Cancer ResearchReceptor Platelet-Derived Growth Factor alphamedicine.medical_treatmentT celltumor cell proliferationPDGFRAGrowth factor receptorCell Line TumormedicinePDFGRASTAT5 Transcription FactorHumansAutocrine signallingExtracellular Signal-Regulated MAP KinasesSTAT5PTCL/NOS; PDFGRA; tumor cell proliferationCell ProliferationPlatelet-Derived Growth FactorbiologyCell growthExtracellular Signal-Regulated MAP KinaseGrowth factorLymphoma T-Cell PeripheralHematologyPTCL/NOSdigestive system diseasesGene expression profilingAutocrine Communicationmedicine.anatomical_structureAnesthesiology and Pain MedicineSTAT1 Transcription FactorOncologyCancer researchbiology.proteinT-cell lymphomaProto-Oncogene Proteins c-aktHuman
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CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death

2011

Abstract Extracellular adenosine (ADO), generated from ATP or ADP through the concerted action of the ectoenzymes CD39 and CD73, elicits autocrine and paracrine effects mediated by type 1 purinergic receptors. We have tested whether the expression of CD39 and CD73 by chronic lymphocytic leukemia (CLL) cells activates an adenosinergic axis affecting growth and survival. By immunohistochemistry, CD39 is widely expressed in CLL lymph nodes, whereas CD73 is restricted to proliferation centers. CD73 expression is highest on Ki-67+ CLL cells, adjacent to T lymphocytes, and is further localized to perivascular areas. CD39+/CD73+ CLL cells generate ADO from ADP in a time- and concentration-dependen…

AdenosineCellular differentiationChronic lymphocytic leukemia5'-Nucleotidase; Adenosine; Adenosine Diphosphate; Adenosine Triphosphate; Antigens CD; Antineoplastic Agents Phytogenic; Apyrase; Autocrine Communication; Cell Death; Cell Differentiation; Cell Movement; Cell Survival; Etoposide; Extracellular Space; GPI-Linked Proteins; Humans; Leukemia Lymphocytic Chronic B-Cell; Paracrine Communication; Receptor Adenosine A2A; Tumor Cells Cultured; Biochemistry; Immunology; Hematology; Cell BiologyMICROENVIRONMENTCD38BiochemistryACTIVATIONAdenosine TriphosphateCell MovementPhytogenichemic and lymphatic diseasesTumor Cells CulturedChronic5'-NucleotidaseEtoposideLeukemiaCulturedCell DeathTUMOR-GROWTHApyrasePurinergic receptorCell DifferentiationHematologyLymphocyticCDTumor CellsCell biologyAdenosine DiphosphateAutocrine CommunicationLeukemiaReceptorIMMUNE SUPPRESSIONReceptor Adenosine A2ACell SurvivalImmunologyAntineoplastic AgentsAdenosinergicBiologyGPI-Linked ProteinsDAMAGE-INDUCED APOPTOSISAdenosine A2AParacrine signallingAntigens CDParacrine CommunicationmedicineHumansAntigensAutocrine signallingImmunobiologyB-CellCell BiologyDAMAGE-INDUCED APOPTOSIS; T-CELLS; IMMUNE SUPPRESSION; ZAP-70 EXPRESSION; TUMOR-GROWTH; RECEPTOR; CD73; ACTIVATION; CD38; MICROENVIRONMENTmedicine.diseaseAntineoplastic Agents PhytogenicLeukemia Lymphocytic Chronic B-CellSettore MED/15 - MALATTIE DEL SANGUET-CELLSCD73Extracellular SpaceZAP-70 EXPRESSIONCD38Blood
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Pulmonary Adenocarcinoma With Enteric Differentiation: Immunohistochemistry and Molecular Morphology

2018

Pulmonary adenocarcinoma with enteric differentiation (PAED) is a rare subtype of lung adenocarcinoma recently recognized in the WHO classification. It is defined as an adenocarcinoma in which the enteric component exceeds 50% and have to show the expression of at least 1 immunohistochemical marker of enteric differentiation. Although the definition of this tumor type is very important, above all in the differential diagnosis between a primary lung tumor and a metastasis of colorectal adenocarcinoma, this cancer still lacks a distinctive immunohistochemical and molecular signature. We recruited the largest series in the literature of PAEDs according to the morphology and the positivity for …

0301 basic medicinePathologymedicine.medical_specialtyLung NeoplasmsHistologyintestinal-type adenocarcinomaCellular differentiationDNA Mutational AnalysisThyroid Nuclear Factor 1AdenocarcinomaBiologymedicine.disease_causePathology and Forensic MedicineMetastasisDiagnosis DifferentialProto-Oncogene Proteins p21(ras)03 medical and health sciences0302 clinical medicineKRASBiomarkers TumormedicineHumansCDX2 Transcription FactorPathology Molecularenteric lung adenocarcinoma intestinal-type adenocarcinoma CDX-2 CDX2 KRASLungKeratin-7entericCancerCell DifferentiationPulmonary adenocarcinoma with enteric differentiation (PAED)lung adenocarcinomamedicine.diseaseCDX-2ImmunohistochemistryMedical Laboratory Technology030104 developmental biologymedicine.anatomical_structureCDX2Alveolar Epithelial Cells030220 oncology & carcinogenesisMutationAdenocarcinomaImmunohistochemistryKRASDifferential diagnosisColorectal Neoplasms
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2.35 CD73-Generated Extracellular Adenosine Creates Microenvironmental Conditions Favoring Growth and Survival of Chronic Lymphocytic Leukemia Cells

2011

Abstract Abstract 621 CD39 (ecto-nucleoside-triphosphate-diphosphohydrolase-1) and CD73 (5'-nucleotidase) are surface enzymes with extracellular catalytic sites. CD39 hydrolyses ATP/ADP to AMP, which is then converted to adenosine (ADO) by CD73. Once ADO is released in the extracellular milieu, it may re-enter the cell or engage different types of purinergic receptors, eliciting potent autocrine and paracrine cytoprotective, anti-inflammatory and immunosuppressive effects. Several lines of evidence suggest that the tumor microenvironment is marked by increased turnover of extracellular nucleotides and nucleosides, as well as by upregulation of ecto-enzymes that dismantle them. These alterat…

Cancer ResearchTumor microenvironmentbusiness.industryChronic lymphocytic leukemiaPurinergic receptorHematologymedicine.disease5'-nucleotidaseLeukemiaParacrine signallingOncologyImmunologyCancer researchExtracellularmedicineAutocrine signallingbusinessClinical Lymphoma Myeloma and Leukemia
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Cell of origin markers identify different prognostic subgroups of lung adenocarcinoma

2018

Strong prognostic markers able to stratify lung adenocarcinoma (ADC) patients are lacking. We evaluated whether a six-immunohistochemical markers panel (TTF1, SP-A, Napsin A, MUC5AC, CDX2 and CK5), defining the putative neoplastic “cell of origin,” allows to identify prognostic subgroups among lung ADC. We screened a large cohort of ADC specimens (2003–2013) from Torino Institutional Repository identifying: (i) marker positivity by immunohistochemistry, (ii) main morphological appearance by light microscopy, (iii) presence of “hotspot” mutations of candidate genes by Sequenom technology. To evaluate possible predictors of survival and time to recurrence, uni- and multivariable-adjusted comp…

Lung adenocarcinomaMorphologyAdultMale0301 basic medicineOncologyBiomarkers; Genetic mutations; Immunohistochemistry; Lung adenocarcinoma; Morphology; Survival analysisPathologymedicine.medical_specialtyCandidate geneCell of originsix-immunohistochemical markers panel (TTF1 SP-A Napsin A MUC5AC CDX2 and CK5)Adenocarcinoma of LungKaplan-Meier Estimategenetic mutationsGene mutationBiologymedicine.disease_causeadenocarcinoma (ADC)survival analysisPathology and Forensic Medicine03 medical and health sciences0302 clinical medicineInternal medicinemorphologyBiomarkers TumormedicineHumansCDX2Survival analysisAgedbiomarkers; genetic mutations; immunohistochemistry; lung adenocarcinoma; morphology; survival analysisbiomarkersSurvival analysisMiddle Agedrespiratory systemPrognosislung adenocarcinomamedicine.diseaseImmunohistochemistryGenetic mutations030104 developmental biology030220 oncology & carcinogenesisimmunohistochemistryAdenocarcinomaImmunohistochemistryFemaleKRASBiomarkersHuman Pathology
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Pathogenetic and diagnostic significance of microRNA deregulation in peripheral T-cell lymphoma not otherwise specified

2014

Peripheral T-cell lymphomas not otherwise specified (PTCLs/NOS) are rare and aggressive tumours whose molecular pathogenesis and diagnosis are still challenging. The microRNA (miRNA) profile of 23 PTCLs/NOS was generated and compared with that of normal T-lymphocytes (CD4+, CD8+, naive, activated). The differentially expressed miRNA signature was compared with the gene expression profile (GEP) of the same neoplasms. The obtained gene patterns were tested in an independent cohort of PTCLs/NOS. The miRNA profile of PTCLs/NOS then was compared with that of 10 angioimmunoblastic T-cell lymphomas (AITLs), 6 anaplastic large-cell lymphomas (ALCLs)/ALK+ and 6 ALCLs/ALK - . Differentially expressed…

Female; Gene Expression Profiling; Humans; Lymphoma T-Cell Peripheral; Male; MicroRNAs; Oligonucleotide Array Sequence Analysis; RNA Neoplasm; Gene Expression Regulation Neoplastic; Oncology; Hematology; Medicine (all)Malemedicine.medical_specialtyPathologyPeripheral T-cell lymphoma not otherwise specifiedBiologyhemic and lymphatic diseasesInternal medicinemicroRNAmedicineHumansRNA NeoplasmOligonucleotide Array Sequence AnalysisRegulation of gene expressionHematologymicroRNA; PTCLs/NOS; GEPOligonucleotide Array Sequence AnalysiGene Expression ProfilingMedicine (all)Not Otherwise SpecifiedLymphoma T-Cell PeripheralMicroRNAHematologymedicine.diseaseGEPLymphomaGene expression profilingGene Expression Regulation NeoplasticMicroRNAsOncologyPTCLs/NOSOriginal ArticleFemaleCD8Human
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Molecular profiling of blastic plasmacytoid dendritic cell neoplasm reveals a unique pattern and suggests selective sensitivity to NF-kB pathway inhi…

2014

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease of controversial origin recently recognized as a neoplasm deriving from plasmacytoid dendritic cells (pDCs). Nevertheless, it remains an orphan tumor with obscure biology and dismal prognosis. To better understand the pathobiology of BPDCN and discover new targets for effective therapies, the gene expression profile (GEP) of 25 BPDCN samples was analyzed and compared with that of pDCs, their postulated normal counterpart. Validation was performed by immunohistochemistry (IHC), whereas functional experiments were carried out ex vivo. For the first time at the molecular level, we definitely recognized the cellular derivati…

EXPRESSIONMyeloidCancer ResearchPathologymedicine.medical_specialtyMyeloidCell Cycle; Dendritic Cells; Humans; Leukemia Myeloid Acute; NF-kappa B; Signal Transduction; Gene Expression Profiling; Hematology; Cancer Research; Anesthesiology and Pain MedicineAcuteBiologyCell Cycle; Dendritic Cells; Humans; Leukemia Myeloid Acute; NF-kappa B; Signal Transduction; Gene Expression ProfilingDendritic CellArticleMALIGNANCIESMULTIPLE-MYELOMABlastic plasmacytoid dendritic cell neoplasmBlastic plasmacytoid dendritic cell neoplasm; anti-NF-kB-treatment; GEPGene expressionmedicineHumansNeoplasmanti-NF-kB-treatmentGene Expression ProfilingCell CycleNF-kappa BleukemiaIN-VITRODendritic CellsHematologyBlastic plasmacytoid dendritic cell neoplasmmedicine.diseaseCANCERGEPFACTOR-KAPPA-BLeukemia Myeloid AcuteSettore MED/15 - MALATTIE DEL SANGUEDIFFERENTIATIONAnesthesiology and Pain Medicinemedicine.anatomical_structureLYMPHOID PATHWAYSOncologyCell cultureHEMATODERMIC NEOPLASMImmunohistochemistryCellular modelEx vivoHumanSignal Transduction
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