Examinando por Autor "Hunter, Keith D"

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    Pitfalls in odontogenic lesions and tumours: a practical guide
    (Elsevier Ltd, 2020-12) Hunter, Keith D; Niklander, Sven
    Lesions arising from odontogenic tissues of the jaws vary from very common to very rare. Some, such as radicular cysts, form a routine part of the diagnostic workload for histopathologists who report specimens from the head and neck, but many other lesions are rarely seen and can cause significant diagnostic difficulty for the non-specialist. These issues are compounded by the vagaries of dental disease (and terminology used by dentists and oral surgeons) and issues in the interpretation of radiographic images, which can be crucial to making a correct diagnosis. In this review article, we will discuss a number of areas of diagnostic difficulty, largely based on the authors experience in receiving tertiary referrals. This will focus on practical advice to help avoid the pitfalls in the diagnosis of odontogenic lesions.
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    The role of icIL-1RA in keratinocyte senescence and development of the senescence-associated secretory phenotype
    (Company of Biologists Ltd, 2021-02) Sven E., Niklander,; Hannah L, Crane,; Lav, Darda,; Lambert, Daniel W.; Hunter, Keith D
    There is compelling evidence that senescent cells, through the senescence-associated secretory phenotype (SASP), can promote malignant transformation and invasion. Interleukin-1 (IL-1) is a key mediator of this cytokine network, but the control of its activity in the senescence programme has not been elucidated. IL-1 signalling is regulated by IL-1RA, which has four variants. Here, we show that expression of intracellular IL-1RA type 1 (icIL-1RA1), which competitively inhibits binding of IL-1 to its receptor, is progressively lost during oral carcinogenesis ex vivo and that the pattern of expression is associated with keratinocyte replicative fate in vitro. We demonstrate that icIL-1RA1 is an important regulator of the SASP in mortal cells, as CRISPR/Cas9-mediated icIL-1RA1 knockdown in normal and mortal dysplastic oral keratinocytes is followed by increased IL-6 and IL-8 secretion, and rapid senescence following release from RhoA-activated kinase inhibition. Thus, we suggest that downregulation of icIL-1RA1 in early stages of the carcinogenesis process can enable the development of a premature and deregulated SASP, creating a pro-inflammatory state in which cancer is more likely to arise. © 2021 Company of Biologists Ltd. All rights reserved.