Background: The immune suppression mechanisms in pancreatic ductal adenocarcinoma (PDAC) remain unknown, but preclinical studies have implicated macrophage-mediated immune tolerance. Hence, pathways that regulate macrophage phenotype are of strategic interest, with reprogramming strategies focusing on inhibitors of phosphoinositide 3-kinase-gamma (PI3Kγ) due to restricted immune cell expression. Inhibition of PI3Kγ alone is ineffective in PDAC, despite increased infiltration of CD8+ T cells.
View Article and Find Full Text PDFPurpose: Advanced prostate cancer (PCa) is invariably fatal with the androgen receptor (AR) being a major therapeutic target. AR signaling inhibitors have improved overall survival for men with advanced PCa, but treatment resistance is inevitable and includes reactivation of AR signaling. Novel therapeutic approaches targeting these mechanisms to block tumor growth is an urgent unmet clinical need.
View Article and Find Full Text PDFPhilos Trans R Soc Lond B Biol Sci
January 2025
Zoonotic and vector-borne infectious diseases are among the most direct human health consequences of biodiversity change. The COVID-19 pandemic increased health policymakers' attention on the links between ecological degradation and disease, and sparked discussions around nature-based interventions to mitigate zoonotic emergence and epidemics. Yet, although disease ecology provides an increasingly granular knowledge of wildlife disease in changing ecosystems, we still have a poor understanding of the net consequences for human disease.
View Article and Find Full Text PDFTumor initiation represents the first step in tumorigenesis during which normal progenitor cells undergo cell fate transition to cancer. Capturing this process as it occurs in vivo, however, remains elusive. Here we employ spatiotemporally controlled oncogene activation and tumor suppressor inhibition together with multiomics to unveil the processes underlying oral epithelial progenitor cell reprogramming into tumor initiating cells at single cell resolution.
View Article and Find Full Text PDFBackground: Reducing the prevalence and consequences of anxiety following childbirth (postpartum anxiety) is a strategic priority in the UK and many similar nations; a comprehensive review of risk factors can support the development of interventions and guide further research.
Methods: This registered systematic review was guided by 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' (PRISMA) and analysed using 'Synthesis Without Meta-analysis' (SWiM) to answer the question; 'What factors have been reported to increase the risk of maternal postpartum anxiety (PPA) in Australia, Europe, and North America?'. MEDLINE and PsycINFO were searched for relevant research from Australia, Europe, and North America, published up to July 2021.