Project description:Circulating tumor DNA (ctDNA) as a biomarker of disease activity in classic Hodgkin lymphoma (cHL) patients are still not well-defined. By profiling primary tumors and ctDNA, we identified common variants between primary tumors and longitudinal plasma samples in most of the cases, confirming high PBatial and temporal heterogeneity. Though ctDNA analyses mirrored HRS cell genetics overall, the prevalence of variants shows that none of them can be used as a single biomarker. Conversely, the estimation of hGE/mL, based in total ctDNA quantification, reflects disease activity and is almost perfectly correlated with standard parameters such as PET/CT that are associated with refractoriness.
Project description:Intrinsic subtyping of breast cancer was performed using an nCounter RUO-PAM50 gene expression assay to determine the ability of instrinsic subtyping to predict what patients may benefit from altered chemotherapy scheduling in the CALGB 9741 clinical trial population. FFPE primary breast tumor samples archived at the CALGB Pathology Coordinating Office (PCO) were used to obtain total RNA for instrinsic subtyping using the nCounter Analysis System. Gene-expression profiles were generated for 1321 of 1471 patient samples (90%) suitable for inclusion in this study.
Project description:Intrinsic subtyping of breast cancer was performed using an nCounter RUO-PAM50 gene expression assay to determine the ability of instrinsic subtyping to predict what patients may benefit from altered chemotherapy scheduling in the CALGB 9741 clinical trial population.
Project description:1. Primary Endpoints
* Biomarker data suggestive of regorafenib-mediated inhibition of the RAS-RAF- MEK-ERK signal transduction pathway,of various tyrosine kinase receptors and/or of angiogenesis.
* Evaluation of potential relationships between biomarker data and clinical activity.
* Evaluation of a novel biomarker technology (Prometheus COPIA platform)
2. Secondary Endpoints
* Biomarker data suggestive of regorafenib-mediated effects on circulating rare cells.
* Comparison of tumor genetic profiles obtained using DNA isolated from plasma, tumor biopsies and circulating tumor cells.
* Patient safety data
* Pharmacokinetics of regorafenib
* Changes in tumor metabolic activity as measured by PET CT scan (optional)
Project description:In this study, we display traceable impact of energetically-varying CT irradiation on gene regulation with common upregulation of five radiation-responsive genes after single-energy (80 kV or 150kV) and dual-energy CT (80kV + 150kV) exposure. Furthermore, no evdidence for an elevated radiobiological effectiveness in respect to transcriptional impact of low energy photons emitted during dual-energy CT was found.
Project description:Autism spectrum disorder (ASD) has increased over ten-fold over the past several decades, and appears predominantly associated with paternal transmission. Although genetics is anticipated to be a component of ASD etiology, environmental epigenetics is now thought to be an important factor. Epigenetic alterations, such as DNA methylation have been correlated with ASD. The current study was designed to identify a DNA methylation signature in sperm as a potential biomarker to identify paternal offspring autism susceptibility. Sperm samples were obtained from fathers, many undergoing in vitro fertilization (IVF) procedures, that have children with or without autism, and the sperm then assessed for alterations in DNA methylation. Differential DNA methylation regions (DMRs) were identified in the sperm of fathers with autistic children in comparison to those without ASD children. An MeDIP-seq procedure was used to identify DMRs. The genomic features and genes associated with the DMRs were identified. The potential sperm DMR biomarker was validated with a blinded test set of individuals. Observations demonstrate a significant set of DMRs in sperm can potentially act as a biomarker for paternal offspring autism susceptibility.