0000000001149851

AUTHOR

Osvaldo Graña

showing 2 related works from this author

Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts

2016

Item does not contain fulltext Inflammation has important roles in tissue regeneration, autoimmunity, and cancer. Different inflammatory stimuli can lead to bone loss by mechanisms that are not well understood. We show that skin inflammation induces bone loss in mice and humans. In psoriasis, one of the prototypic IL-17A-mediated inflammatory human skin diseases, low bone formation and bone loss correlated with increased serum IL-17A levels. Similarly, in two mouse models with chronic IL-17A-mediated skin inflammation,K14-IL17A(ind)andJunB(Deltaep), strong inhibition of bone formation was observed, different from classical inflammatory bone loss where osteoclast activation leads to bone deg…

0301 basic medicineMaleInflammationModels BiologicalOsteocytesBone resorptionEpithelium03 medical and health sciences0302 clinical medicineOsteoclastOsteogenesismedicineAnimalsHumansPsoriasisCell LineageBone ResorptionWnt Signaling PathwaySkin030203 arthritis & rheumatologyInflammationOsteoblastsChemistryInnate lymphoid cellInterleukin-17Wnt signaling pathwayOsteoblastGeneral MedicineMiddle AgedMice Inbred C57BL030104 developmental biologymedicine.anatomical_structureGene Expression RegulationOsteocyteImmunologyChronic DiseaseCancer researchFemaleInterleukin 17medicine.symptomInflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5]Science Translational Medicine
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Genomic Profiling of Patient-Derived Xenografts for Lung Cancer Identifies B2M Inactivation Impairing Immunorecognition

2017

Abstract Purpose: We aimed to maximize the performance of detecting genetic alterations in lung cancer using high-throughput sequencing for patient-derived xenografts (PDXs). Experimental Design: We undertook an integrated RNA and whole-exome sequencing of 14 PDXs. We focused on the genetic and functional analysis of β2-microglobulin (B2M), a component of the HLA class-I complex. Results: We identified alterations in genes involved in various functions, such as B2M involved in immunosurveillance. We extended the mutational analysis of B2M to about 230 lung cancers. Five percent of the lung cancers carried somatic mutations, most of which impaired the correct formation of the HLA-I complex. …

0301 basic medicineCancer ResearchLungHuman leukocyte antigenBiologymedicine.diseaseImmunosurveillance03 medical and health sciences030104 developmental biologymedicine.anatomical_structureOncologyDownregulation and upregulationImmunologymedicineCancer researchCytotoxic T cellLung cancerExome sequencingCD8Clinical Cancer Research
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