Publications by authors named "R K McEwen"
Purpose: Here, we report the sensitivity of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay (Signatera) for detection of molecular relapse during long-term follow-up of patients with breast cancer.
Methods: A total of 156 patients with primary breast cancer were monitored clinically for up to 12 years after surgery and adjuvant chemotherapy. Semiannual blood samples were prospectively collected, and analyzed retrospectively to detect residual disease by ultradeep sequencing using ctDNA assays, developed from primary tumor whole-exome sequencing data.
Article Synopsis
- - The PI3K-AKT pathway is often active in breast cancer, and inhibitors targeting this pathway, like capivasertib and AZD8186, are used in treatments, but the reasons for resistance to these therapies aren't well understood on a broad scale.
- - CRISPR screenings identified key genes that lead to treatment resistance, revealing that reactivation of PI3K-AKT-mTOR signaling is the primary mechanism, while deletion of certain genes can either confer resistance or increase sensitivity to these drugs.
- - Loss of Mcl-1 enhances the effectiveness of PI3K-AKT inhibitors by promoting faster cell death, and combining Mcl-1 inhibitors with PI3K-AKT inhibitors shows promise for overcoming resistance in various breast
Article Synopsis
- A study was conducted to assess a comprehensive behavior change intervention aimed at reducing unnecessary antibiotic use in hospitals by encouraging prescribers to make appropriate decisions during clinical reviews.
- The research utilized a randomized controlled trial across multiple hospitals in the UK, tracking outcomes such as antibiotic dosage and patient mortality within 30 days post-admission through electronic health records and audits.
- The effectiveness of the intervention was analyzed using time series methods and random-effects meta-analysis, with the study now completed and registered for validation.
Purpose: To examine the prevalence and dynamics of circulating tumor DNA (ctDNA) and its association with metastatic recurrence in patients with high-risk early-stage hormone receptor-positive breast cancer (HR+ BC) more than 5 years from diagnosis.
Methods: We enrolled 103 patients with high-risk stage II-III HR+ BC diagnosed more than 5 years prior without clinical evidence of recurrence. We performed whole-exome sequencing (WES) on primary tumor tissue to identify somatic mutations tracked via a personalized, tumor-informed ctDNA test to detect minimal residual disease (MRD).
We describe a new liquid tissue stamping method called poly-synchronous surface extraction (PSSE) that utilizes an omniphobic substrate patterned with hydrophilic surface energy traps (SETs), which when wet with a solvent form a dense microdroplet array. When contacted with a tissue sample, each droplet locally extracts analytes from the tissue surface, which subsequentially can be analyzed by matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-IMS) or ambient ionization-MS techniques. Optimization of the patterned surface with six different solvents was carried out to increase the droplet density, height, and reproducibility of volume deposition.
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