Treatment of psoriasis

Psoriasis is a prevalent chronic inflammatory disease. Beyond skin and joint manifestations, psoriasis has numerous associated comorbidities, including metabolic and cardiovascular disease. There are many treatment options available, from topical treatment for mild psoriasis, phototherapy for moderate disease, to systemic therapy or biological agents for severe disease. This article aims to focus on the treatment for the majority of patients where topical agents alone are generally appropriate.http://www.sapj.co.za/index.php/sapjam2021Dental Management Science

Elevated levels of soluble CTLA-4, PD-1, PD-L1, LAG-3 and TIM-3 and systemic inflammatory stress as potential contributors to immune suppression and generalized tumorigenesis in a cohort of South African Xeroderma pigmentosum patients

Xeroderma Pigmentosum (XP), an autosomal recessive disorder characterized by ultraviolet radiation-induced abnormalities of DNA excision and repair pathways is associated with early development of cutaneous cancers. Intracellular oxidative stress has also been proposed as a contributor to the occurrence of skin cancers. However, little is known about the possible augmentative contributions of chronic inflammation, immune suppression and oxidative stress to the pathogenesis of malignancies associated with other subtypes of XP. This has been addressed in the current study, focused on the measurement of systemic biomarkers of inflammation, immune dysfunction and oxidative damage in XP patients, consisting of XP-C, XP-D and XP-E cases, including those XP-C cases who had already developed multiple skin malignancies. The inflammatory biomarker profile measured in XP patients and healthy control subjects included the cytokines, interleukins (ILs)-2, -4, -6, -10, interferon-γ (IFN- γ) and tumor-necrosis factor-α (TNF-α), the acute phase reactant, C-reactive protein (CRP), and cotinine (as an objective indicator of smoking status). Immune suppression was detected according to the levels of five soluble inhibitory immune checkpoint proteins (CTLA-4, PD-1, PD-L1, LAG-3 and TIM-3), as well as those of vitamin D, while oxidative stress was determined according to the circulating levels of the DNA adduct, 8-hydroxy-2-deoxyguanosine (8-OH-dG). These various biomarkers were measured in plasma using immunofluorimetric, nephelometric and ELISA procedures. Significant elevations in IL-6 (P<0.01) and TNF-α (P<0.0001), but none of the other cytokines, as well as increased levels of all five soluble inhibitory immune checkpoints (P=0.032-P=0.0001) were detected in the plasma of the XP patients. C-reactive protein and vitamin D were increased and decreased, respectively (both P<0.0001), while only one participant had an elevated level of plasma cotinine. Surprisingly, the levels of 8-OH-dG were significantly (P=0.0001) lower in the group of XP patients relative to a group of healthy control subjects. The findings of increased levels of pro-inflammatory cytokines and, in particular, those of the soluble immune checkpoints, in the setting of decreased vitamin D and moderately elevated levels of CRP in XP patients suggest a possible secondary role of ongoing, inflammatory stress and immune suppression in the pathogenesis of XP-associated malignancies.University of Pretoria.https://www.frontiersin.org/journals/oncologydm2022ImmunologyNuclear Medicin

AI and precision oncology in clinical cancer genomics : from prevention to targeted cancer therapies-an outcomes based patient care

Precision medicine is the personalization of medicine to suit a specific group of people or even an individual patient, based on genetic or molecular profiling. This can be done using genomic, transcriptomic, epigenomic or proteomic information. Personalized medicine holds great promise, especially in cancer therapy and control, where precision oncology would allow medical practitioners to use this information to optimize the treatment of a patient. Personalized oncology for groups of individuals would also allow for the use of population group specific diagnostic or prognostic biomarkers. Additionally, this information can be used to track the progress of the disease or monitor the response of the patient to treatment. This can be used to establish the molecular basis for drug resistance and allow the targeting of the genes or pathways responsible for drug resistance. Personalized medicine requires the use of large data sets, which must be processed and analysed in order to identify the particular molecular patterns that can inform the decisions required for personalized care. However, the analysis of these large data sets is difficult and time consuming. This is further compounded by the increasing size of these datasets due to technologies such as next generation sequencing (NGS). These difficulties can be met through the use of artificial intelligence (AI) and machine learning (ML). These computational tools use specific neural networks, learning methods, decision making tools and algorithms to construct and improve on models for the analysis of different types of large data sets. These tools can also be used to answer specific questions. Artificial intelligence can also be used to predict the effects of genetic changes on protein structure and therefore function. This review will discuss the current state of the application of AI to omics data, specifically genomic data, and how this is applied to the development of personalized or precision medicine on the treatment of cancer.The South African Medical Research Council (SAMRC) and the National Research Foundation (NRF).https://www.elsevier.com/locate/imuhj2023Anatomical PathologyMaxillo-Facial and Oral SurgeryMedical OncologyOtorhinolaryngologyRadiologySurgeryUrolog

Systemic levels of the soluble co-inhibitory immune checkpoints, CTLA-4, LAG-3, PD-1/PD-L1 and TIM-3 are markedly increased in basal cell carcinoma

Although co-inhibitory immune checkpoint proteins are primarily involved in promoting cell-cell interactions that suppress adaptive immunity, especially tumor immunity, the soluble cell-free variants of these molecules are also detectable in the circulation of cancer patients where they retain immunosuppressive activity. Nevertheless, little is known about the systemic levels of these soluble co-inhibitory immune checkpoints in patients with various subtypes of basal cell carcinoma (BCC), which is the most invasive and treatment-resistant type of this most commonly-occurring malignancy. In the current study, we have measured the systemic concentrations of five prominent co-inhibitory immune checkpoints, namely CTLA-4, LAG-3, PD-1/PD-L1 and TIM-3, as well as those of C-reactive protein (CRP) and vitamin D (VD), in a cohort of patients (n = 40) with BCC, relative to those of a group of control participants, using the combination of multiplex bead array, laser nephelometry and ELISA technologies, respectively. The median systemic concentrations of CRP and VD were comparable between the two groups; however, those of all five immune checkpoints were significantly elevated (P = 0.0184 - P = < 0.00001), with those of CTLA-4 and PD-1 being highly correlated (r = 0.87; P < 0.00001). This seemingly novel finding not only identifies the existence of significant systemic immunosuppression in BCC, but also underscores the therapeutic promise of immune checkpoint targeted therapy, as well as the potential of these proteins to serve as prognostic/predictive biomarkers in BCC.The study was supported by research funds provided by the University of Pretoria.http://www.elsevier.com/locate/tranonam2023Immunolog