Background: Disorders of gut-brain interaction (DGBIs) present a significant burden on global healthcare systems, yet their underlying mechanisms remain poorly understood. Emerging evidence suggests a role for unconscious psychological processes, particularly attention. This study seeks to detect unconscious attention patterns in people meeting DGBI diagnostic criteria using electroencephalographic (EEG) fast periodic visual stimulation (FPVS), a novel passive method offering high temporal resolution.
View Article and Find Full Text PDFPurpose: Prognostic and predictive biomarkers to cyclin-dependent kinases 4 and 6 inhibitors are lacking. Circulating tumor DNA (ctDNA) can be used to profile these patients and dynamic changes in ctDNA could be an early predictor of treatment efficacy. Here, we conducted plasma ctDNA profiling in patients from the PEARL trial comparing palbociclib+fulvestrant versus capecitabine to investigate associations between baseline genomic landscape and on-treatment ctDNA dynamics with treatment efficacy.
View Article and Find Full Text PDFPurpose: To determine (i) the relationship between candidate biomarkers of the antiproliferative (Ki67) response to letrozole and palbociclib alone and combined in ER/HER2 breast cancer; and (ii) the pharmacodynamic effect of the agents on the biomarkers.
Experimental Design: 307 postmenopausal women with ER/HER2 primary breast cancer were randomly assigned to neoadjuvant treatment with letrozole for 14 weeks; letrozole for 2 weeks, then letrozole+palbociclib to 14 weeks; palbociclib for 2 weeks, then letrozole+palbociclib to 14 weeks; or letrozole+palbociclib for 14 weeks. Biopsies were taken at baseline, 2 and 14 weeks and surgery at varying times after stopping palbociclib.
Debate continues as to whether an attentional bias towards threat displayed by sufferers of functional gastrointestinal disorders (FGIDs) is conscious and, thus, more amenable to change through psychological therapy. We compared the amplitudes of early (unconscious) and later (conscious) electroencephalographic (EEG) event-related potentials following silent reading of symptom-related, emotionally neutral, and emotionally negative nouns across two participant groups: 30 female FGID-sufferers who met diagnostic criteria for irritable bowel syndrome or functional dyspepsia, and 30 female healthy controls. Analogous indices based on alpha desynchronization were also examined, as were correlations between the EEG-based indices and a range of psychosocial variables.
View Article and Find Full Text PDFThe genomics of advanced breast cancer (ABC) has been described through tumour tissue biopsy sequencing, although these approaches are limited by geographical and temporal heterogeneity. Here we use plasma circulating tumour DNA sequencing to interrogate the genomic profile of ABC in 800 patients in the plasmaMATCH trial. We demonstrate diverse subclonal resistance mutations, including enrichment of HER2 mutations in HER2 positive disease, co-occurring ESR1 and MAP kinase pathway mutations in HR + HER2- disease that associate with poor overall survival (p = 0.
View Article and Find Full Text PDFPurpose: mutations are acquired frequently in hormone receptor-positive metastatic breast cancer after prior aromatase inhibitors. We assessed the clinical utility of baseline circulating tumor DNA (ctDNA) analysis in the two phase III randomized trials of fulvestrant versus exemestane.
Experimental Design: The phase III EFECT and SoFEA trials randomized patients with hormone receptor-positive metastatic breast cancer who had progressed on prior nonsteroidal aromatase inhibitor therapy, between fulvestrant 250 mg and exemestane.
JAMA Oncol
October 2019
Importance: Current treatment cures most cases of early-stage, primary breast cancer. However, better techniques are required to identify which patients are at risk of relapse.
Objective: To assess the clinical validity of molecular relapse detection with circulating tumor DNA (ctDNA) analysis in early-stage breast cancer.
Histopathology
January 2017
Aims: Recent literature suggests that clinically silent, microscopic gastrointestinal stromal tumours (micro-GISTs) are common incidental findings. The aim of this study was to examine the histological, immunohistochemical and molecular characteristics of these tumours, which we have defined as measuring ≤20 mm, in order to determine whether the rate and spectrum of mutations are similar to those of clinically symptomatic gastrointestinal stromal tumours (GISTs).
Methods And Results: Thirteen micro-GISTs identified as incidental findings in patients undergoing management of concomitant disease were tested for KIT/PDGFRA mutations.