3 research outputs found
Neutrophilic urticarial dermatosis preceding adult-onset Still's disease
No full textNeutrophilic urticarial dermatosis is a distinct entity strongly associated with underlying autoinflammatory disease. The pathogenesis of this condition has been considered to center around interleukin-1. We report a young woman with neutrophilic urticarial dermatosis who presented with a recurrent urticarial rash for two years prior to the onset of other systemic features including persistent fevers, sore throat, leukocytosis, elevated ferritin, and splenomegaly. She was ultimately diagnosed with adult-onset Still disease and responded well to treatment with systemic corticosteroids. Although neutrophilic urticarial dermatosis is known to occur in the setting of systemic symptoms and disease, its occurrence preceding the onset of systemic inflammation is less well-described in current literature
The Tumour Microenvironment and Epigenetic Regulation in BRCA1 Pathogenic Variant-Associated Breast Cancers
No full textBackground/Objectives: BRCA1 pathogenic variant (PV)-associated breast cancers are most commonly seen in hereditary genetic conditions such as the autosomal-dominant Hereditary Breast and Ovarian Cancer (HBOC) syndrome, and rarely in sporadic breast cancer. Such breast cancers tend to exhibit greater aggressiveness and poorer prognoses due to the influence of BRCA1 pathogenic variants (PVs) on the tumour microenvironment. Additionally, while the genetic basis of BRCA1 PV breast cancer is well-studied, the role of epigenetic mediators in the tumourigenesis of these hereditary breast cancers is also worth exploring. Results: PVs in the BRCA1 gene interact with stromal cells and immune cells, promoting epithelial–mesenchymal transition, angiogenesis, and affecting oestrogen levels. Additionally, BRCA1 PVs contribute to breast cancer development through epigenetic effects on cells, including DNA methylation and histone acetylation, leading to the suppression of proto-oncogenes and dysregulation of cytokines. In terms of epigenetics, lysine-specific demethylase 1 (LSD-1) is considered a master epigenetic regulator, governing both transcriptional repression and activation. It exerts epigenetic control over BRCA1 and, to a lesser extent, BRCA2 genes. The upregulation of LSD-1 is generally associated with a poorer prognosis in cancer patients. In the context of breast cancer in BRCA1/2 PV carriers, LSD-1 contributes to tumour development through various mechanisms. These include the maintenance of a hypoxic environment and direct suppression of BRCA1 gene expression. Conclusions: While LSD-1 itself does not directly cause mutations in BRCA1 or BRCA2 genes, its epigenetic influence sheds light on the potential role of LSD-1 inhibitors as a therapeutic approach in managing breast cancer, particularly in individuals with BRCA1/2 PVs. Targeting LSD-1 may help counteract its detrimental effects and provide a promising avenue for therapy in this specific subgroup of breast cancer
