A5020424520- Prostate Cancer Treatment and Research
- Prostate Cancer Diagnosis and Treatment
- Fibroblast Growth Factor Research
- Cancer, Lipids, and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- Cancer, Hypoxia, and Metabolism
- Kruppel-like factors research
- Bladder and Urothelial Cancer Treatments
- PARP inhibition in cancer therapy
- Mass Spectrometry Techniques and Applications
- Epigenetics and DNA Methylation
- Wnt/β-catenin signaling in development and cancer
- Cell Adhesion Molecules Research
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Cancer-related gene regulation
- Estrogen and related hormone effects
- Cancer Genomics and Diagnostics
- Molecular Biology Techniques and Applications
- Receptor Mechanisms and Signaling
- Cancer Immunotherapy and Biomarkers
- Proteoglycans and glycosaminoglycans research
- Advanced Proteomics Techniques and Applications
- Metabolism, Diabetes, and Cancer
- Cancer Mechanisms and Therapy
University of Glasgow
2016-2025
Queen Elizabeth University Hospital
2016-2025
Cancer Research UK Scotland Institute
2015-2024
Cancer Research UK
2009-2024
NHS Greater Glasgow and Clyde
2009-2024
Newcastle University
2001-2023
Beatson West of Scotland Cancer Centre
2019-2023
Glasgow Life
2015-2020
Institute of Cancer Research
2014-2020
Roche (France)
2019
Abstract BACKGROUND Histone deacetylase 1 (HDAC1) is a co‐repressor involved in differentiation and proliferation control. It upregulated malignant compared to benign tissue, targets number of transcription factors including p53. METHODS By immunohistochemistry, HDAC1 protein expression was investigated human prostate specimens the CWR22 mouse xenograft model. Flow cytometry deconvolution immunofluorescence were also performed. RESULTS pre‐malignant lesions, with highest increase hormone...
Enhanced macromolecule biosynthesis is integral to growth and proliferation of cancer cells. Lipid has been predicted be an essential process in However, it unclear which enzymes within this pathway offer the best selectivity for cells could suitable therapeutic targets. Using functional genomics, we identified stearoyl-CoA desaturase (SCD), enzyme that controls synthesis unsaturated fatty acids, as breast prostate SCD inhibition altered cellular lipid composition impeded cell viability...
Abstract Despite the clinical success of Androgen Receptor (AR)-targeted therapies, reactivation AR signalling remains main driver castration-resistant prostate cancer (CRPC) progression. In this study, we perform a comprehensive unbiased characterisation LNCaP cells chronically exposed to multiple inhibitors (ARI). Combined proteomics and metabolomics analyses implicate an acquired metabolic phenotype common in ARI-resistant associated with perturbed glucose lipid metabolism. To exploit...
Abstract The androgen receptor (AR) is a member of the nuclear steroid hormone family and thought to play an important role in development both androgen-dependent androgen-independent prostatic malignancy. Elucidating roles by which cofactors regulate AR transcriptional activity may provide therapeutic advancement for prostate cancer (PCa). DEAD box RNA helicase p68 (Ddx5) was identified as novel AR-interacting protein yeast two-hybrid screening, we sought examine involvement signaling PCa....
While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We investigated the reasons for this shortcoming, focusing on hurdles downstream biomarker verification, and describe major obstacles possible solutions to ease valid implementation. Some problems lie suboptimal discovery validation, especially lack validated platforms with well-described performance characteristics support qualification. These issues acknowledged being...
Abstract Purpose: Although Src family kinase (SFK) inhibitors are now in clinical trials for the treatment of androgen-independent prostate cancer (AIPC), there no studies relating SFK activation to patient survival. This study was designed determine if up-regulated with development AIPC and patients could be selected who were more likely respond therapy. Experimental Design: A unique cohort matched tumor samples, taken before hormone deprivation therapy following relapse, used by...
Androgen-deprivation therapy (ADT) is standard treatment for locally advanced or metastatic prostate cancer (PCa). Many patients develop castration resistance (castration-resistant PCa [CRPC]) after approximately 2-3 yr, with a poor prognosis. The molecular mechanisms underlying CRPC progression are unclear.
The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer (PCa) randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. To determine report outcomes according treatment received in randomised choice cohorts. This study focuses on secondary care. Men clinically at one nine UK centres were invited participate the comparing AM, Two cohorts included 1643 who agreed be randomised; 997 declined randomisation chose...
High cholesterol may be a modifiable risk factor for prostate cancer but results have been inconsistent and subject to potential "reverse causality" where undetected disease modifies prior diagnosis.We conducted prospective cohort study of 12,926 men who were enrolled in the Midspan studies between 1970 1976 followed up 31st December 2007. We used Cox-Proportional Hazards Models evaluate association baseline plasma Gleason grade-specific incidence. excluded cancers detected within at least 5...
Pancreatic ductal adenocarcinoma (PDAC) is often lethal because it highly invasive and metastasizes rapidly. The actin-bundling protein fascin has been identified as a biomarker of advanced PDAC regulates cell migration invasion in vitro. We investigated expression its role progression mice.
Significance Using an unbiased forward mutagenesis screen, we were able to successfully identify candidate genes that drive advanced and metastatic prostate cancer (CaP). Alterations of peroxisome proliferator-activated receptor gamma ( PPARG ), encoding a regulator crucial lipid metabolism, appear play role in the development CaP both humans mice.
We report fundamental insights into the validity, reliability and clinical feasibility of using heterogeneous Pd catalysts as implantable devices to accurately activate chemotherapy within a tumour.
Abstract Background Prostate cancer (PC) is the commonest male visceral cancer, and second leading cause of mortality in men Western world. Methods Using a forward-mutagenesis Sleeping Beauty (SB) transposon-based screen Probasin Cre-Recombinase ( Pb-Cre ) Pten -deficient mouse model PC, we identified Arid1a loss as driver development metastatic disease. Results The insertion transposon gene resulted 60% reduction expression, reduced tumour free survival SB:Pten fl/fl INT median 226 days vs...
RAC 3, one of the p160 family co-activators is known to enhance transcriptional activity a number steroid receptors. As are also androgen receptor (AR) activity, we investigated role 3 in context prostate cancer. In cancer cell lines, found variable levels protein with highest expression seen AR-positive LNCaP cells, moderate AR-negative PC cells and low-level DU 145 cells. Immuno-precipitation studies showed that endogenous interacted AR vivo transfection assays confirmed enhanced activity....
Abstract The Sprouty proteins are increasingly being recognized to be deregulated in various types of cancers. This deregulation is often associated with aberrant signaling receptor tyrosine kinases and its downstream effectors, leading the mitogen-activated protein kinase (MAPK) pathway. In human hepatocellular carcinoma, where MAPK activity enhanced via multiple hepatocarcinogenic factors, we observed a consistent reduced expression sprouty 2 (Spry2) transcript malignant hepatocytes...
We report a phase I/II clinical trial in prostate cancer (PCa) using direct intraprostatic injection of replication defective adenovirus vector (CTL102) encoding bacterial nitroreductase (NTR) conjunction with systemic prodrug CB1954. One group patients localized PCa scheduled for radical prostatectomy received virus alone, prior to surgery, dose escalation establish safety, tolerability, and NTR expression. A second local failure following primary treatment plus safety tolerability. Based...
Abstract Fibroblast growth factor receptors (FGFRs) mediate the tumourigenic effects of FGFs in prostate cancer. These are therefore potential therapeutic targets development inhibitors to this pathway. To identify most relevant targets, we simultaneously investigated FGFR1–4 expression using a cancer tissue microarray (TMA) and laser capture microdissected (LCM) epithelial cells. In malignant prostates ( n = 138) observed significant FGFR1 FGFR4 protein over‐expression comparison with...