5 research outputs found
Epigenetic regulation of prostate cancer
Prostate cancer is a commonly diagnosed cancer in men and a leading cause of cancer deaths. Whilst the underlying mechanisms leading to prostate cancer are still to be determined, it is evident that both genetic and epigenetic changes contribute to the development and progression of this disease. Epigenetic changes involving DNA hypo- and hypermethylation, altered histone modifications and more recently changes in microRNA expression have been detected at a range of genes associated with prostate cancer. Furthermore, there is evidence that particular epigenetic changes are associated with different stages of the disease. Whilst early detection can lead to effective treatment, and androgen deprivation therapy has a high response rate, many tumours develop towards hormone-refractory prostate cancer, for which there is no successful treatment. Reliable markers for early detection and more effective treatment strategies are, therefore, needed. Consequently, there is a considerable interest in the potential of epigenetic changes as markers or targets for therapy in prostate cancer. Epigenetic modifiers that demethylate DNA and inhibit histone deacetylases have recently been explored to reactivate silenced gene expression in cancer. However, further understanding of the mechanisms and the effects of chromatin modulation in prostate cancer are required. In this review, we examine the current literature on epigenetic changes associated with prostate cancer and discuss the potential use of epigenetic modifiers for treatment of this disease
Switching Between Biological Treatments in Psoriatic Arthritis: A Review of the Evidence
Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy. Therapy with anti-tumor necrosis factor (TNF)-α agents represents the first therapeutic choice for moderate and severe forms; however, PsA patients can experience anti-TNFα failure, lack of efficacy, or adverse events. Several evidences exist on the effectiveness of switching among different TNFα inhibitors, and we reviewed the published data on the effectiveness of anti-TNFα first-, second- and third-line. Most of the studies report that the main reason for switching to a second anti-TNFα agent is represented by lack of efficacy (primary or secondary) and, more rarely, adverse events. Switchers receiving their second anti-TNFα agent have considerably poorer responses compared with non-switchers. Survival of anti-TNFα treatment appears to be superior in PsA patients when compared with rheumatoid arthritis patients. Switching from anti-TNF agents to ustekinumab or secukinumab or apremilast can represent a valid alternative therapeutic strategy
Switching Between Biological Treatments in Psoriatic Arthritis: A Review of the Evidence
The Use of Cyclosporine A in Rheumatology: a 2016 Comprehensive Review
Cyclosporine A, an inhibitor of calcineurin, exerts an immunomodulator action interfering with T cell activation. Even though novel therapeutic tools have emerged, CyA still represents a suitable option in several clinical rheumatology settings. This is the case of refractory nephritis and cytopenias associated with systemic lupus erythematosus. Furthermore, CyA is a valued therapeutic tool in the management of uveitis and thrombophlebitis in course of Behçet's disease. Topical CyA has been proven to be beneficial in the dry eye of Sjogren's syndrome, whereas oral treatment with CyA can be considered for the severe complications of adult onset Still's disease. CyA provides a therapeutic option in psoriatic arthritis, being rather effective in skin disease. CyA is currently regarded as a second-line option for patients with inflammatory myopathies refractory to standard regimen. CyA is used even in paediatric rheumatology, in particular in the management of juvenile dermatomyositis and macrophage activation syndrome associated with systemic juvenile idiopathic arthritis. Importantly, CyA has been shown to suppress the replication of HCV, and it can thus be safely prescribed to those patients with chronic hepatitis C. Noteworthy, CyA can be administered throughout the gestation course. Surely, caution should be paid to CyA safety profile, in particular to its nephrotoxicity. Even though most evidence comes from small and uncontrolled studies with few randomised controlled trials, CyA should be still regarded as a valid therapeutic tool in 2016 rheumatology