A5085023615- Angiogenesis and VEGF in Cancer
- Ovarian cancer diagnosis and treatment
- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Endometrial and Cervical Cancer Treatments
- Prenatal Screening and Diagnostics
- Colorectal Cancer Screening and Detection
- Cancer-related molecular mechanisms research
- Endometriosis Research and Treatment
- Liver Disease Diagnosis and Treatment
- Pancreatitis Pathology and Treatment
- Global Cancer Incidence and Screening
- Cancer Risks and Factors
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cancer-related gene regulation
- Extracellular vesicles in disease
- Kruppel-like factors research
- Neuroendocrine Tumor Research Advances
- Protease and Inhibitor Mechanisms
- Ubiquitin and proteasome pathways
- Uterine Myomas and Treatments
- Complementary and Alternative Medicine Studies
- Lymphatic System and Diseases
University College London
2015-2025
MRC Clinical Trials Unit at UCL
2019-2024
Breast Cancer Now
2013-2019
Imperial College London
2001-2018
University College Hospital
2009-2017
Royal Victoria Hospital
2016
Belfast City Hospital
2016
Liverpool Women's Hospital
2016
University Hospital of Wales
2016
James Cook University Hospital
2016
Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect early detection by screening on ovarian mortality.
Abstract The ubiquitin-proteasome system is a major regulatory pathway of protein degradation and plays an important role in cellular division. Fbxw7 (or hCdc4), member the F-box family proteins, which are substrate recognition components multisubunit ubiquitin ligase SCF (Skp1-Cdc53/Cullin-F-box-protein), has been shown to mediate ubiquitin-dependent proteolysis several oncoproteins including cyclin E1, c-Myc, c-Jun, Notch. oncogenic potential substrates, frequent allelic loss human...
Background Recent studies have shown that DNA methylation (DNAm) markers in peripheral blood may hold promise as diagnostic or early detection/risk for epithelial cancers. However, to date no study has evaluated the and predictive potential of such a large case control cohort on genome-wide basis. Principal Findings By performing DNAm profiling ovarian cancer cohort, we here demonstrate active significant impact pattern blood. Specifically, by measuring levels over 27,000 CpGs cells from 148...
Purpose Cancer screening strategies have commonly adopted single-biomarker thresholds to identify abnormality. We investigated the impact of serial biomarker change interpreted through a risk algorithm on cancer detection rates. Patients and Methods In United Kingdom Collaborative Trial Ovarian Screening, 46,237 women, age 50 years or older underwent incidence by using multimodal strategy (MMS) in which annual serum antigen 125 (CA-125) was with ovarian (ROCA). Women were triaged ROCA:...
The epigenetic phenomenon of genomic imprinting provides an additional level gene regulation that is confined to a limited number genes, frequently, but not exclusively, important for embryonic development. evolution and maintenance has been linked the balance between allocation maternal resources developing fetus mother's well being. Genes are imprinted in both embryo extraembryonic tissues show extensive conservation mouse human. Here we examine human orthologues genes only placenta,...
Biomarkers for the early detection of pancreatic cancer are urgently needed. The primary objective this study was to evaluate whether increased levels serum CA19-9, CA125, CEACAM1, and REG3A present before clinical presentation assess performance combined markers prognosis.This nested case-control within UKCTOCS included 118 single 143 serial samples from 154 postmenopausal women who were subsequently diagnosed with 304 matched noncancer controls. Samples split randomly into independent...
BackgroundEpigenetic changes are emerging as one of the most important events in carcinogenesis. Two alterations pattern DNA methylation breast cancer (BC) have been previously reported; active estrogen receptor-α (ER-α) is associated with decreased ER-α target (ERT) genes, and polycomb group (PCGT) genes more likely than other to promoter hypermethylation cancer. However, whether normal unrelated cells BC risk these imprints can be related factors which modified by environment,...
Blood-borne biomarkers for early detection of colorectal cancer (CRC) could markedly increase screening uptake. The aim this study was to evaluate serum carcinoembryonic antigen (CEA), CYFRA21-1 and CA125 the CRC in an asymptomatic cohort.This nested case-control within UKCTOCS used 381 serial samples from 40 women subsequently diagnosed with CRC, 20 benign disease matched non-cancer controls three four per subject taken annually up 4 years before diagnosis. CEA, were measured using...
In UKCTOCS, there was a decrease in the diagnosis of advanced stage tubo-ovarian cancer but no reduction deaths multimodal screening group compared with group. Therefore, we did exploratory analyses patients high-grade serous ovarian to understand reason for discrepancy.
Genomic imprinting is limited to a subset of genes that play critical roles in fetal growth, development and behaviour. One the most studied imprinted encodes insulin-like growth factor 2, aberrant DNA methylation this gene associated with disorders Beckwith–Wiedemann Silver–Russell syndromes many human cancers. Specific isoforms have been shown be essential for normal placental function, as mice carrying paternal null alleles Igf2-P0 transcript are restricted at birth. We report here...
Identification of serum biomarkers enabling earlier diagnosis pancreatic ductal adenocarcinoma (PDAC) could improve outcome. Serum protein profiles in patients with preclinical disease and at were investigated.
Objectives: The negative publicity about menopausal hormone therapy (MHT) has led to increased use of complementary and alternative medicines (CAM) non-pharmacological interventions (NPI) for symptom relief. We report on the prevalence predictors CAM/NPI among UK postmenopausal women.Method: Postmenopausal women aged 50–74 years were invited participate in Collaborative Trial Ovarian Cancer Screening (UKCTOCS). A total 202 638 recruited completed a baseline questionnaire. Of these, 136 020...
There are widespread efforts to increase symptom awareness of 'pelvic/abdominal pain, increased abdominal size/bloating, difficulty eating/feeling full and urinary frequency/urgency' in an attempt diagnose ovarian cancer earlier. Long-term survival women with these symptoms adjusted for known prognostic factors is yet be determined. This study explored the association symptoms, routes interval diagnosis long-term a population-based cohort postmenopausal diagnosed invasive epithelial...
Abstract Objective To estimate the risk of primary epithelial ovarian cancer (EOC) and slow growing borderline or Type I aggressive II EOC in postmenopausal women with adnexal abnormalities on ultrasound. Methods This was a prospective cohort study ultrasound group UK Collaborative Trial Ovarian Cancer Screening ultrasound‐detected abnormal (unilocular, multilocular, unilocular solid multilocular solid, solid) morphology their first scan. Women were followed up through national registries by...
The objective of this study was to investigate the hypothesis that altered epigenetic mechanisms regulate IGF2 imprinting in placentas from fetal growth restricted (FGR) pregnancies affect expression leading impaired growth. We investigated gene transcription, genotyping and methylation patterns 31 17 FGR-complicated normal pregnancies, respectively. A statistically significant decrease mRNA levels observed FGR pregnancies. Loss (LOI) only detected abnormal placentas. evaluation percentage...
Abstract Background Earlier detection of pancreatic ductal adenocarcinoma (PDAC) is key to improving patient outcomes, as it mostly detected at advanced stages which are associated with poor survival. Developing non-invasive blood tests for early would be an important breakthrough. Methods The primary objective the work presented here use a dataset that prospectively collected, quantify set cancer-associated proteins and construct multi-marker models capacity predict PDAC years before...
DNA methylation of polycomb group target (PCGT) genes is an early step in carcinogenesis and could potentially be assayed to determine cancer risk prediction. To assess whether changes PCGT normal tissue able predict the presence cancer, we studied HOXA gene endometrium from premenopausal ovarian patients age-matched healthy controls without cancer. HOXA9 HOXA11 was associated with initial test set this subsequently confirmed independent validation sample sets. The overall increased...
Cervical cancer is the second most common type of in women worldwide. Preinvasive disease can be detected by cervical cytology. All currently available cytology technologies rely on visual analysis exfoliated cells from uterine cervix. Improvement conventional cytological screening has been proposed introduction molecular-based markers applied to liquid-based (LBC), suspension collected DNA methylation changes occur very early carcinogenesis and identification appropriate such samples should...
Abstract Background Participants in trials evaluating preventive interventions such as screening are on average healthier than the general population. To decrease this 'healthy volunteer effect' (HVE) women were randomly invited from population registers to participate United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and not allowed self refer. This report assesses extent HVE still prevalent UKCTOCS considers how certain shortfalls mortality incidence can be related...
Better use of healthcare systems data, collected as part interactions between patients and the system, could transform planning conduct randomised controlled trials. Multiple challenges to widespread include whether data captures sufficiently well traditionally captured on case report forms. "Data Utility Comparison Studies" (DUCkS) assess utility for RCTs by comparison trial. Despite their importance, there are few published UK examples DUCkS. Building from ongoing selected recent UK-led...