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Discoid lupus erythematosus is an autoimmune connective‐tissue disease that represents a subset of conditions on the cutaneous lupus spectrum. The lesions are characterized by disk‐shaped plaques on photo‐exposed skin with inflammatory hyperpigmentation and adherent scale. Here, we present a patient with a rare manifestation of discoid lesions on the palms. [ABSTRACT FROM AUTHOR]

Background and Purpose: Adenosine A2A receptor stimulation promotes the synthesis of collagen type I and type III (Col1 and Col3), mediators of fibrosis and scarring. The A2A receptor modulates collagen balance via cAMP/PKA/p38-MAPK/Akt pathways. Wnt signalling is important in fibrosis and the cAMP and Wnt pathways converge. Because the A2A receptor is Gs-linked and increases cAMP, we determined whether A2A receptors and Wnt signalling interact.Experimental Approach: Total β-catenin, de-phosphorylated β-catenin (canonical activation, de-phospho β-catenin) and phosphorylated β-catenin at Ser552 (non-canonical activation, p-Ser552 β-catenin) levels were determined in primary human dermal fibroblasts, cytosol and nucleus, by western blot analysis and fluorescence microscopy, before and after stimulation by A2A receptor-selective agonist CGS21680, with/without A2A receptor-selective antagonist (SCH56261) pretreatment. β-Catenin was knocked down by transfection with scrambled-siRNA or specific-siRNA, and Col1 and Col3 levels determined by western blots.Key Results: CGS21680 stimulation rapidly (15 min) increased cellular β-catenin levels. Both de-phospho β-catenin and p-Ser552 β-catenin levels were also increased. CGS21680 stimulated the translocation of total de-phospho and p-Ser552 β-catenin to the nucleus. A2A receptor-stimulation increased Col1 synthesis similarly in β-catenin knockeddown and scrambled cells. However, β-catenin knockdown abolished the increase in Col3 synthesis induced in A2A receptor-stimulated fibroblasts.Conclusions and Implications: A2A receptor stimulation promotes Col3 synthesis via the activation of canonical and non-canonical β-catenin, consistent with a role for A2A receptors in dermal fibrosis and scarring. [ABSTRACT FROM AUTHOR]

Collagen and matrix deposition by fibroblasts is an essential part of wound healing but also contributes to pathologic remodeling of organs leading to substantial morbidity and mortality. Adenosine, a small molecule generated extracellularly from adenine nucleotides as a result of direct stimulation, hypoxia, or injury, acts via a family of classical seven-pass G protein-coupled protein receptors, A and A, leading to generation of cAMP and activation of downstream targets such as PKA and Epac. These effectors, in turn, lead to fibroblast activation and collagen synthesis. The regulatory actions of these receptors likely involve multiple interconnected pathways, and one of the more interesting aspects of this regulation is opposing effects at different levels of cAMP generated. Additionally, adenosine signaling contributes to fibrosis in organ-specific ways and may have opposite effects in different organs. The development of drugs that selectively target these receptors and their signaling pathways will disrupt the pathogenesis of fibrosis and slow or arrest the progression of the important diseases they underlie. [ABSTRACT FROM AUTHOR]

Ponatinib induces a persistent molecular response and graft-versus-host disease/graft-versus-leukemia effect in a patient with Philadelphia-positive acute lymphoblastic leukemia with a T315I mutation following early relapse after allogeneic transplant. Ponatinib is a third-generation tyrosine kinase inhibitor (TKI) that has demonstrated efficacy for treatment of imatinib-resistant leukemias. A 50-year-old African American women with a 23-year medical history of chronic myeloid leukemia (CML) presented with a painful rash on her chest, breast, axillae, upper back, and bilateral lower extremities. [Extracted from the article]