7 research outputs found
Evaluation of serum CEA, CYFRA21-1 and CA125 for the early detection of colorectal cancer using longitudinal preclinical samples
Blood-borne biomarkers for early detection of colorectal cancer (CRC) could markedly increase screening uptake. The aim of this study was to evaluate serum carcinoembryonic antigen (CEA), CYFRA21-1 and CA125 for the early detection of CRC in an asymptomatic cohort
Transcriptional Activation of the Adenoviral Genome Is Mediated by Capsid Protein VI
Gene expression of DNA viruses requires nuclear import of the viral genome. Human
Adenoviruses (Ads), like most DNA viruses, encode factors within early
transcription units promoting their own gene expression and counteracting
cellular antiviral defense mechanisms. The cellular transcriptional repressor
Daxx prevents viral gene expression through the assembly of repressive chromatin
remodeling complexes targeting incoming viral genomes. However, it has remained
unclear how initial transcriptional activation of the adenoviral genome is
achieved. Here we show that Daxx mediated repression of the immediate early Ad
E1A promoter is efficiently counteracted by the capsid protein VI. This requires
a conserved PPxY motif in protein VI. Capsid proteins from other DNA viruses
were also shown to activate the Ad E1A promoter independent of Ad gene
expression and support virus replication. Our results show how Ad entry is
connected to transcriptional activation of their genome in the nucleus. Our data
further suggest a common principle for genome activation of DNA viruses by
counteracting Daxx related repressive mechanisms through virion proteins
Stool-Based Colorectal Cancer Screening Test Performance Characteristics in Those With and Without Hemorrhoids
Objective: To evaluate the effect of hemorrhoids on noninvasive stool test performance for colorectal cancer (CRC) screening. Patients and Methods: We conducted a retrospective cohort study of test characteristics for the fecal immunochemical test (FIT) and the multitarget stool DNA (mt-sDNA) test, on the basis of hemorrhoid status, recorded at the time of colonoscopy, among patients enrolled in the pivotal prospective study for mt-sDNA that was conducted from June 2011, to May 2013. Test characteristics (sensitivity, specificity, positive, and negative predictive values) for FIT and mt-sDNA (performed < 90 days before colonoscopy) were stratified by the presence of hemorrhoids and compared. Results: Hemorrhoids were found in 51.7% (5163 of 9989) of the study cohort. Across all test characteristics, there were no statistically significant differences for FIT or mt-sDNA when stratified by hemorrhoid status. Analysis revealed mt-sDNA sensitivity of 44% and 41% for advanced precancerous lesions in nonhemorrhoidal and hemorrhoid patients, respectively (P=.41). The FIT sensitivity among the same lesion category was 24.9% in patients without hemorrhoids and 22.8% in those with hemorrhoids (P=.48). The mt-sDNA specificity was 86.4% in patients without hemorrhoids vs 87.7% in those with hemorrhoids (P=.67), although FIT specificity was 95.0% among patients without hemorrhoids vs 94.7% in those with hemorrhoids (P=.44). Conclusion: The presence of asymptomatic hemorrhoids did not adversely affect test performance in this large clinical study. These findings suggest that in the absence of overt gastrointestinal bleeding, FIT and mt-sDNA are options for CRC screening, irrespective of hemorrhoid status. Trial Registration: clinicaltrials.gov Identifier: NCT0139774