- Prostate Cancer Treatment and Research
- Prostate Cancer Diagnosis and Treatment
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Advanced Radiotherapy Techniques
- Urologic and reproductive health conditions
- Genetic Syndromes and Imprinting
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- Amino Acid Enzymes and Metabolism
- Bladder and Urothelial Cancer Treatments
- Urinary and Genital Oncology Studies
- Urological Disorders and Treatments
- Cancer, Lipids, and Metabolism
- Prenatal Screening and Diagnostics
- COVID-19 and healthcare impacts
- Pancreatic function and diabetes
- TGF-β signaling in diseases
- Diet and metabolism studies
- Cancer-related molecular mechanisms research
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- Global Cancer Incidence and Screening
- Patient Satisfaction in Healthcare
- Cancer, Hypoxia, and Metabolism
Royal Surrey NHS Foundation Trust
2020-2025
Cancer Research UK
2009-2020
University of Cambridge
2008-2020
Royal Surrey County Hospital
2017-2020
Cancer Research UK Cambridge Center
2010-2011
Hammersmith Hospital
2009
Cohesin is a chromatin-associated protein complex that mediates sister chromatid cohesion by connecting replicated DNA molecules. also has important roles in gene regulation, but the mechanistic basis of this function poorly understood. In mammalian genomes, cohesin co-localizes with CCCTC binding factor (CTCF), zinc finger implicated multiple regulatory events. At imprinted IGF2-H19 locus, CTCF plays an role organizing allele-specific higher-order chromatin conformation and functions as...
Environmental factors interact with the genome throughout life to determine gene expression and, consequently, tissue function and disease risk. One such factor that is known play an important role in determining long-term metabolic health diet during critical periods of development. Epigenetic regulation has been implicated mediating these programming effects early diet. The precise epigenetic mechanisms underlie remain largely unknown. Here, we show transcription Hnf4a , which etiology...
The imprinted insulin-like growth factor 2 (IGF2) gene is expressed predominantly from the paternal allele. Loss of imprinting (LOI) associated with hypomethylation at promoter proximal sequence (DMR0) IGF2 was proposed as a predisposing constitutive risk biomarker for colorectal cancer. We used pyrosequencing to assess whether DMR0 methylation either present constitutively prior cancer or it acquired tissue-specifically after onset DNA samples tumour tissues and matched non-tumour 22 breast...
Abstract Long noncoding RNAs (lncRNAs) regulate gene expression via their RNA product or through transcriptional interference, yet a strategy to differentiate these two processes is lacking. To address this, we used multiple small interfering (siRNAs) silence GNG12-AS1 , nuclear lncRNA transcribed in an antisense orientation the tumour-suppressor DIRAS3 . Here show that while most siRNAs post-transcriptionally, siRNA complementary exon 1 of suppresses its transcription by recruiting...
The discovery of cytosine hydroxymethylation (5hmC) as a mechanism that potentially controls DNA methylation changes typical neoplasia prompted us to investigate its behaviour in colon cancer. 5hmC is globally reduced proliferating cells such tumours and the gut crypt progenitors, from which can arise. Here, we show colorectal cancer express Ten-Eleven-Translocation (TET) transcripts at levels similar normal tissues. Genome-wide analyses promoters marked by tissue, those identified TET2...
Ketone bodies have both metabolic and epigenetic roles in cancer. In several studies, they showed an anti-cancer effect via inhibition of histone deacetylases; however, other studies observed faster tumour growth. The related molecule butyrate also inhibits growth some cancer cells accelerates it others. This "butyrate paradox" is thought to be due mediating acetylation thus inhibiting cell proliferation cancers that preferentially utilise glucose (the Warburg effect); whereas oxidise as a...
The transforming growth factor beta (TGF-β) signaling pathway exerts opposing effects on cancer cells, acting as either a tumor promoter or suppressor. Here, we show that these are result of the synergy between SMAD3, downstream effector TGF-β signaling, and distinct epigenomes breast-tumor-initiating cells (BTICs). These associated with gene expression programs, but genomic SMAD3 binding patterns highly similar in BTIC-promoting BTIC-suppressing contexts. Our data cell-type-specific DNA...
To report oncological and functional outcomes of men treated with low-dose-rate (LDR) prostate brachytherapy aged ≤60 years at time treatment.Of 3262 patients LDR our centre up to June 2016, we retrospectively identified 597 treatment ≥3-years post-implantation follow-up four prostate-specific antigen (PSA) measurements, which one was baseline. Overall survival (OS), cancer-specific (PCSS) relapse free (RFS) were analysed together prospectively collected physician-reported adverse events...
Background: Colorectal cancer (CRC) progression from adenoma to adenocarcinoma is associated with global reduction in 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). DNA hypomethylation continues upon liver metastasis. Here we examine 5hmC changes Results: increased metastatic tissue relative the primary colon tumour expression of TET2 TET3 negatively correlated risk for metastasis patients CRC. Genes show KEGG enrichment adherens junctions, cytoskeleton cell migration around a...
Abstract Background Colorectal cancer (CRC) progression from adenoma to adenocarcinoma is associated with global reduction in 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). DNA hypomethylation continues upon liver metastasis. Here we examine 5hmC changes Results increased metastatic tissue relative the primary colon tumour expression of TET2 TET3 negatively correlated risk for metastasis patients CRC. Genes show KEGG enrichment adherens junctions, cytoskeleton cell migration...
Abstract Cytosine hydroxymethylation (5hmC) in mammalian DNA is the product of oxidation methylated cytosines (5mC) by Ten-Eleven-Translocation (TET) enzymes. While it has been shown that TETs influence 5mC metabolism, pluripotency and differentiation during early embryonic development, functional relationship between gene expression 5hmC adult (somatic) stem cell still unknown. Here we report levels undergo highly dynamic changes from intestinal progenitors to differentiated epithelium. We...
Abstract The archetypal epigenetic phenomenon of position effect variegation (PEV) in Drosophila occurs when a gene is brought abnormally close to heterochromatin, resulting stochastic silencing the affected proportion cells that would normally express it. PEV has been instrumental unraveling mechanisms. Using an vivo mammalian model for we have extensively investigated molecular basis heterochromatin-mediated silencing. Here distinguish 'epigenetic effects' from other cellular differences...
To report clinical outcomes of the Hemi-Ablative Prostate Brachytherapy (HAPpy) trial evaluating treatment-related toxicity and effectiveness hemi-gland (HG) low-dose-rate (LDR) prostate brachytherapy as a focal approach to control unilateral localised cancer.Single institution phase IIS pilot study patients treated with 4D Brachytherapy™ (BXTAccelyon, Burnham, Buckinghamshire, UK). The primary outcome was patient-reported 24 months after implant. secondary assessment disease control....
<h3>ABSTRACT</h3> <h3>Objective</h3> To evaluate urology patient satisfaction with telephone consultations during the COVID-19 pandemic. <h3>Methods</h3> All patients who received a appointment in 1-month period were invited to complete questionnaire. An adaption of Telehealth Satisfaction Scale (TeSS) was used. Patient responses compared based on type clinic, age and gender. <h3>Results</h3> 119 questionnaires completed. The majority adapted TeSS (Q1–7) graded as 'Excellent', ranging from...
To report clinical outcomes of 125 I low-dose-rate prostate brachytherapy (LDR-PB) as monotherapy or combined with androgen-deprivation therapy (ADT) and/or external beam radiotherapy (EBRT) in high-risk localised cancer.Analysis from a prospective cohort patients treated LDR-PB alone treatment single institution. Men high risk disease relapse were identified by the National Institute for Health and Care Excellence (NICE) criteria Comprehensive Cancer Network (NCCN) criteria. Relapse-free...
To report the incidence of malignancy in gynaecological organs removed during radical cystectomy (RC).
To report clinical and functional outcomes for patients who have undergone salvage robot-assisted seminal vesicle excision (RA-SVE) the focal treatment of isolated vesical (SV) recurrence after prostate cancer by low-dose-rate brachytherapy.Patients with rising prostate-specific antigen (PSA) brachytherapy (LDR-PB) underwent multi-parametric magnetic resonance imaging (mp-MRI) 11 C-Choline or 68 Ga-prostate-specific membrane (68 Ga-PSMA) positron emission tomography/computed tomography...