Project description:TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC). This study looks at the multi-region RNAseq data from the TRACERx100 cohort with high enough quality RNA available. There is RNAseq data from 164 regions (64 patients).
Project description:Infections by the New World alphaviruses, Eastern Equine encephalitis virus (EEEV), Venezuelan Equine encephalitis virus (VEEV), and Western Equine encephalitis virus (WEEV), cause febrile illness that can progress to fatal disease in humans and equids. Currently there are no FDA-approved antivirals for prophylactic or therapeutic treatment of human infection by these viruses. To combat these infections, we have developed a novel small molecule, BDGR-164, which has subnanomolar potency against VEEV, EEEV, and WEEV. Using an intranasal route of virus infection in a lethal BALB/c model, prophylactic subcutaneous administration of BDGR-164 conferred 100% (VEEV), 88% (EEEV), and 63% (WEEV) survival. To evaluate the ability of BDGR-164 to reduce viral RNA/antigen, inflammation, and pathogenesis, we used RNASeq and histopathology of whole brain at 4 days post-infection (dpi). Viral RNA levels and antigen were reduced significantly in virus-infected and BDGR-164-treated versus virus-infected, sham-treated mice. Moreover, there was a significant reduction in host immune responses associated with inflammatory signaling, immune cell recruitment, and programmed cell death in virus-infected, BDGR-164 treated mice. Cytokine analyses of sera corroborated the reduction in upregulation of the immune response in virus-infected, BDGR-164 treated mice. Limited antiviral resistance to BDGR-164 was detected in one mouse on 4 dpi at NSP2:Y102C. In conclusion, our studies suggest that BDGR-164 has broad and potent prophylactic efficacy against the neurotropic alphaviruses.
Project description:Triplicate samples of RAW 264.7 murine macrophages either untreated, stimulated with 100 ng/ml LPS for 18 hours, or constituitively over-expressing CstF-64 were analyzed by microarray using Affymetrix murine gene chip 430A. Keywords = RAW 264.7 macrophages Keywords = LPS Keywords = CstF-64 Keywords: repeat sample