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BACKGROUND Clinical prognostic groupings for localised prostate cancers are imprecise, with 30-50% of patients recurring after image-guided radiotherapy or radical prostatectomy. We aimed to test combined genomic and microenvironmental indices in prostate cancer to improve risk stratification and complement clinical prognostic factors. METHODS We used(More)
Castrate-resistant prostate cancer (CRPC) is poorly characterized and heterogeneous and while the androgen receptor (AR) is of singular importance, other factors such as c-Myc and the E2F family also play a role in later stage disease. HES6 is a transcription co-factor associated with stem cell characteristics in neural tissue. Here we show that HES6 is(More)
In prostate cancer (PC), the androgen receptor (AR) is a key transcription factor at all disease stages, including the advanced stage of castrate-resistant prostate cancer (CRPC). In the present study, we show that GABPα, an ETS factor that is up-regulated in PC, is an AR-interacting transcription factor. Expression of GABPα enables PC cell lines to acquire(More)
BACKGROUND The totally extraperitoneal (TEP) approach is increasingly favoured for inguinal hernia repair. The learning curve is slow with high, early recurrence rates but the exact cause of recurrence is unknown. OBJECTIVE To determine the reasons for recurrence, identify the critical operative steps and examine the influence of surgical experience and(More)
UNLABELLED What's known on the subject? and What does the study add? Ureteric stents cause significant discomfort and this is probably related to ureteric smooth muscle spasm and trigonal irritation. Alpha-adrenoceptor antagonists reduce smooth muscle activity and are already widely used in medical expulsive therapy to aid passage of ureteric calculi. This(More)
BACKGROUND Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome. METHODS In a study of 482 tumour, benign and germline samples from 259 men(More)
Prostate cancer is the most common cancer in men, resulting in over 10 000 deaths/year in the UK. Sequencing and copy number analysis of primary tumours has revealed heterogeneity within tumours and an absence of recurrent founder mutations, consistent with non-genetic disease initiating events. Using methylation profiling in a series of multi-focal(More)
Molecular characterization of genome-wide association study (GWAS) loci can uncover key genes and biological mechanisms underpinning complex traits and diseases. Here we present deep, high-throughput characterization of gene regulatory mechanisms underlying prostate cancer risk loci. Our methodology integrates data from 295 prostate cancer chromatin(More)
BACKGROUND Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates. OBJECTIVE To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial. DESIGN, SETTING, AND PARTICIPANTS Mortality(More)
Castration-resistant prostate cancer (CRPC) continues to pose a significant clinical challenge with new generation second-line hormonal therapies affording limited improvement in disease outcome. As the androgen receptor (AR) remains a critical driver in CRPC, understanding the determinants of its transcriptional activity is important for developing new(More)