A5055768985- Cancer, Stress, Anesthesia, and Immune Response
- Neuropeptides and Animal Physiology
- Prostate Cancer Treatment and Research
- Chemokine receptors and signaling
- Epigenetics and DNA Methylation
- Cervical Cancer and HPV Research
- Bladder and Urothelial Cancer Treatments
- Fibroblast Growth Factor Research
- Cancer-related Molecular Pathways
- Virus-based gene therapy research
- Cystic Fibrosis Research Advances
- Advanced biosensing and bioanalysis techniques
- Ferroptosis and cancer prognosis
- Peptidase Inhibition and Analysis
- Eosinophilic Disorders and Syndromes
- Head and Neck Cancer Studies
- Colorectal and Anal Carcinomas
- Neonatal Respiratory Health Research
- Cellular Mechanics and Interactions
- Protist diversity and phylogeny
- CRISPR and Genetic Engineering
- NF-κB Signaling Pathways
- Urinary and Genital Oncology Studies
- RNA Interference and Gene Delivery
- Cardiomyopathy and Myosin Studies
St James's University Hospital
2010-2022
University of Leeds
2016-2021
University of South Australia
2015
University of York
1995-2013
Yorkshire Cancer Research
1998-2013
Cancer Research UK
2010
University of Nottingham
2008
University of Toronto
1987-2002
York University
1998
Cancer Research UK Scotland Institute
1993-1994
Malignant tumors result from the accumulation of genetic alterations in oncogenes and tumor suppressor genes. Much less is known about changes benign tumors. Seborrheic keratoses (SK) are very frequent human epidermal without malignant potential. We performed a comprehensive mutational screen genes FGFR3-RAS-MAPK phosphoinositide 3-kinase (PI3K)-AKT pathways 175 SK, including multiple lesions each patient. SK commonly harbored bona fide oncogenic mutations FGFR3 , PIK3CA, KRAS HRAS EGFR AKT1...
Understanding the molecular determinants that underpin clinical heterogeneity of non-muscle-invasive bladder cancer (NMIBC) is essential for prognostication and therapy development. Stage T1 disease in particular presents a high risk progression requires improved understanding. We present detailed multi-omics study containing gene expression, copy number, mutational profiles show relationships to immune infiltration, recurrence, muscle invasion. compare expression genomic subtypes derived...
Abstract In prostate cancer, traditional treatments such as androgen response manipulation often provide only temporary resolution of disease, with emergence a more aggressive, androgen-independent tumor following initial therapy. To treat recurrent cell surface proteins that are specifically overexpressed on malignant cells may be useful for generating targeted therapeutics. Recent evidence suggests neurotensin receptors (NTR) recruited in advanced cancer an alternative growth pathway the...
Bladder cancer is the 10th most common worldwide. For muscle-invasive bladder (MIBC), treatment includes radical cystectomy, radiotherapy, and chemotherapy; however, outcome generally poor. non-muscle-invasive (NMIBC), tumor recurrence common. There an urgent need for more effective less harmful therapeutic approaches. Here, cell metabolic reprogramming to rely on aerobic glycolysis (the Warburg effect) expression of associated molecular targets by cells different stages grades, in freshly...
Abstract Background Indoleamine 2,3-dioxygenase (IDO), the first step in kynurenine pathway (KP), is upregulated some cancers and represents an attractive therapeutic target given its role tumour immune evasion. However, recent failure of IDO inhibitor a late phase trial raises questions about this strategy. Methods Matched renal cell carcinoma (RCC) normal kidney tissues were subject to proteomic profiling. Tissue immunohistochemistry gene expression data used validate findings. Phenotypic...
Fibroblast growth factor receptors (FGFRs) are implicated in a range of cancers with several pan-kinase and selective-FGFR inhibitors currently being evaluated clinical trials. Pan-FGFR often cause toxic side effects few examples subtype-selective exist. Herein, we describe structure-guided approach toward the development selective FGFR2 inhibitor. De novo design was carried out on an existing fragment series to yield compounds predicted improve potency against FGFRs. Subsequent iterative...
T-cell-mediated immune responses against mucosal oncogenic types of human papillomaviruses (HPV) are thought to play a role in the control virus infection and its associated cervical lesions. The vitro production interleukin-2 by T-helper (Th) cells response C-terminal N-terminal domains HPV-16 E2 protein was determined 74 women with cytological evidence premalignant epithelial neoplasia who participated non-intervention follow-up (FU) study. Cross-sectional analysis at end FU showed that Th...
In lentiviral gene delivery systems, transgene expression cassettes are commonly cloned without a polyadenylation signal to prevent disruption of full-length genomes on mRNA maturation in producer cells. The lack the signal, however, has potential reduce stability and translation efficiency mRNA. Therefore, we have assessed effect strong internal [poly(A)] both levels virus-infected cells functional viral titer, series eight self-inactivating lentiviruses expressing mOrange under control...
The human papillomavirus type 16 (HPV-16) status of 43 cervical biopsies, which had been characterized histologically as normal, various grades intraepithelial neoplasia (CIN) and invasive squamous cell carcinoma, was examined by using (i) a novel antibody against the HPV-16 E2 protein, (ii) sensitive DNA in situ hybridization (iii) microdissection/PCR for ORF. data indicate that protein expression is highest koilocytes lower-grade CIN (I), but decreases with increasing grade, whereas...
Gene therapy represents an attractive strategy for the non-invasive treatment of prostate cancer, where current clinical interventions show limited efficacy. Here, we evaluate use insect virus, baculovirus (BV), as a novel vector human cancer gene therapy. Since tumours represent heterogeneous environment, therapeutic approach that achieves long-term regression must be capable targeting multiple transformed cell populations. Furthermore, discrimination in malignant compared to non-malignant...
Specific antibodies against the C-terminus of E2, produced by affinity purification polyclonal antisera, have been used to identify cellular populations which express HPV 16 E2 transcription factor, in a series formalin-fixed, paraffin-embedded cervical tissues. Cases were selected for both presence DNA (confirmed multiple gene-specific PCR detections) and grades intraepithelial neoplasia (CIN). The data indicate that expression is highest CIN I koilocytic lesions. Lower was observed II...
Bladder cancers commonly show genetic aberrations in the phosphatidylinositol 3-kinase signaling pathway. Here we have screened for mutations PIK3R1, which encodes p85α, one of regulatory subunits PI3K. Two hundred and sixty-four bladder tumours 41 tumour cell lines were 18 detected. Thirteen C-terminal domains are predicted to interfere with interaction between p85α p110α. Five BH domain PIK3R1. This region has been implicated p110α-independent roles such as binding altering activities...
Papillomavirus E2 proteins play a central role in regulating viral gene expression and replication. DNA-binding activity is associated with the C-terminal domain of E2, which forms stable dimer, while N-terminal responsible for E2's replication transactivation functions. The crystal structure latter revealed second dimerization interface on may be DNA loop formation regulatory region human papillomavirus (HPV) genome. We investigated biological significance by introducing single amino acid...