Videos
Spontaneous mutations in the gene encoding the tumor suppressor p53 (TP53) are frequently identified in human cancers and most of these mutations are the result of missense substitutions, which can result in complete loss of p53 function or retention of some activity. In this episode, Jean Gariépy and Nicholas Fischer discuss their work, which reveals that the level of residual transcriptional activity of mutant p53 associates with improved survival in males with glioma and gastric adenocarcinoma. This association was sex-specific, as similar links were not observed in females with p53-mutant cancers. Moreover, evaluation of patients with Li-Fraumeni syndrome (LFS), which results from germline mutations in TP53 revealed a link between residual p53 activity and prolong lifetime cancer survival. Together, these results support p53 transcriptional activity as a prognostic factor for men with glioma and gastric adenocarcinoma.
Several different factors, including alcohol use and hepatitis C virus (HCV) infection, underlie chronic liver disease. Regardless of the cause, chronic liver disease progress in a similar fashion, ultimately resulting in hepatic fibrosis and loss of organ function. In this episode, Matthew Sweet and colleagues performed gene expression profiling on liver biopsies from patients at different stages of fibrosis with varying disease etiologies. Using this approach, the authors identified genes associated with advanced fibrosis and demonstrated that levels of at least one of the gene products, VCAN, is elevated in serum from patients with advanced fibrosis. Additionally, a set of steatosis-associated genes and serum markers was identified in an HCV patient cohort and validated in a murine model. These common gene signatures have potential as both biomarkers and therapeutic targets of chronic liver disease.
Fetal growth restriction during pregnancy can lead to a variety of complications, including still birth and increased risk of cardiovascular and metabolic disease later in life. Placental volume can be used to predict adverse regency outcomes, including risk of an infant being small for gestational age; however, determination of placental volume is time consuming, requiring an operator to manually identify and annotate the placenta. In this episode, Sally Collins and Pádraig Looney describe the development of a technique that allows for automated segmentation of the placenta and volume determination from 3D ultrasound images. This technique has potential for wide-spread use for predicting small gestational age.
The inflammatory skin disease atopic dermatitis is characterized by decreased epidermal barrier function, susceptibility to S. aureus infection, and immune dysfunction. Recently, the commensal bacterium Roseomonas mucosa was shown to improve atopic dermatitis-like phenotypes in murine models. In this episode, Ian Myles and colleagues evaluate safety and efficacy of topical administration of R. mucosa in a small cohort of adults and children with atopic dermatitis. Overall, R. mucosa treatment was considered safe and reduced disease severity in both children and adults. The results from this initial study supports further evaluation of topical R. mucosa for treating atopic dermatitis.
Type 1 diabetes (T1D) results from autoimmune-mediated destruction of insulin-producing pancreatic β cells. While there is a genetic component to T1D, there is no reliable way to identify which genetically at-risk individuals will develop autoantibodies. In this episode, Mark Harris, Ahmed Mehdi, and Ranjeny Thomas discuss their work, which identifies a gene expression signature during infancy that when combined with HLA risk score predicts later seroconversion in genetically at-risk subjects. Use of this signature has potential to improve early diagnosis and treatment intervention for those at risk of developing T1D.
