A5070059734- Cancer-related Molecular Pathways
- Head and Neck Cancer Studies
- Head and Neck Surgical Oncology
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Oral and Maxillofacial Pathology
- Cancer Research and Treatments
- Bone Tumor Diagnosis and Treatments
- Metabolomics and Mass Spectrometry Studies
- Cancer, Hypoxia, and Metabolism
- HIV-related health complications and treatments
- Renal cell carcinoma treatment
- Oral Health Pathology and Treatment
- Advanced Chemical Sensor Technologies
- Mechanisms of cancer metastasis
- Peptidase Inhibition and Analysis
- HIV Research and Treatment
- Colorectal and Anal Carcinomas
- Lung Cancer Treatments and Mutations
- Reconstructive Surgery and Microvascular Techniques
- Cancer-related gene regulation
- Galectins and Cancer Biology
- Effects of Radiation Exposure
- Protein Degradation and Inhibitors
University of Liverpool
2012-2025
Lagos State University
2017
Aintree University Hospital
2015
Royal Liverpool University Hospital
2002-2012
Aintree University Hospitals NHS Foundation Trust
2010
Weatherford College
2008
Drexel University
2000
Hahnemann University Hospital
2000
Institute of Cancer Research
1991
University of Southampton
1989
Abstract Purpose: To enable the design of improved inhibitors matrix metalloproteinases (MMPs) for treatment pancreatic cancer, expression profiles a range MMPs and tissue (TIMPs) were determined. Experimental Design: Nine (MMPs 1–3, 7–9, 11, 12, 14) three TIMPs (TIMPs 1–3) examined in up to 75 ductal adenocarcinomas 10 normal pancreata by immunohistochemistry. Eighteen additional an eight also analyzed real-time reverse transcription-PCR additionally MMP-15. Results: There was increased...
Predicting when a patient with advanced cancer is dying challenge and currently no prognostic test available. We hypothesised that process from associated metabolic changes specifically in volatile organic compounds (VOCs). analysed urine patients lung the last weeks of life by headspace gas chromatography mass spectrometry. Urine was acidified or alkalinised before analysis. VOC were identified using univariate, multivariate linear regression analysis; 12 VOCs increased (11 acid dataset, 2...
Objectives/Hypothesis The incidence of human papillomavirus (HPV)-driven disease beyond the oropharynx varies greatly in reported literature. Study Design Case series. Methods Two hundred twenty-one samples were strictly classified to subsites oral cavity, larynx, or hypopharynx at time primary surgery. Formalin-fixed paraffin-embedded subjected a validated, tiered, diagnostic algorithm p16 immunohistochemistry, high-risk HPV situ hybridization, and quantitative polymerase chain reaction for...
The MDM2 protein, through its interaction with p53, plays an important role in the regulation of G1 checkpoint cell cycle. In addition to binding and inhibiting transcriptional activation function p53 binds, inter alia, RB E2F-1·DP-1 complex so doing may promote progression cells into S phase. Mice transgenic for Mdm2 possess that have cycle defects develop altered tumor profile independent their status. also blocks growth inhibitory effects transforming factor-β1 a p53-independent manner....
Primary radiotherapy (RT) is a mainstay of treatment for laryngeal squamous cell carcinoma (LSCC). Although the cure rates early (T1) vocal cord tumours are high, RT proves ineffective in up to third T3 carcinomas. Moreover, associated with debilitating early- and late-treatment-related toxicity, thus finding means de-escalate therapy, while retaining/augmenting therapeutic effectiveness, highly desirable. p53 key mediator radiation responses; we therefore investigated whether Nutlin-3,...
The correlation between stress-induced nucleolar disruption and abrogation of p53 degradation is evident after a wide variety cellular stresses. This link may be caused by steps in regulation occurring nucleoli, as suggested some biochemical evidence. Alternatively, also causes redistribution proteins, potentially altering their interactions with and/or MDM2. raises the fundamental question whether nucleolus controls directly, i.e., site where regulatory processes occur, or indirectly,...
Adjuvant fluoropyrimidine-based (5-FU) chemotherapy is a mainstay of treatment for colorectal cancer (CRC), but only provides benefit subset patients. To improve stratification we examined (for the first time in CRC), whether analysis GRP78 expression predictive biomarker and performed functional studies to examine role sensitivity 5-FU. 396 CRC patient samples were collected prospective uniform manner was determined by immunohistochemistry on tissue microarrays using well-validated...
Abstract Background Accurately recognizing that a person may be dying is central to improving their experience of care at the end-of-life. However, predicting frequently inaccurate and often occurs only hours or few days before death. Methods We performed urinary metabolomics analysis on patients with lung cancer create metabolite model predict over last 30 life. Results Here we show model, using 7 metabolites, has excellent accuracy in Training cohort n = 112 (AUC 0·85, 0·88 0·86 5, 10, 20...
p53 is a critical coordinator of wide range stress responses. To facilitate rapid response to stress, produced constitutively but negatively regulated by MDM2. MDM2 can inhibit in multiple independent ways: binding its transcription activation domain, inhibiting acetylation, promoting nuclear export, and probably most importantly proteasomal degradation p53. The latter achieved via MDM2's E3 ubiquitin ligase activity harbored within the RING finger domain. We have discovered that MTBP...
Loss of p53 function is a critical event in tumor evolution. This occurs through range molecular events, typically missense mutation followed by loss heterozygosity. In many cancers, there compelling evidence that cells can compromise have selective advantage. The situation renal cell carcinoma unclear. It has recently been suggested unusually compromised novel dominant, MDM2/p14ARF-independent mechanism. hard to reconcile with other recent studies identified as an important prognostic...
Abstract MDM2 is a ubiquitin ligase that best known for its essential function in the negative regulation of p53. In addition, expression associated with tumor progression number common cancers, and some cases, this has been shown to be independent p53 status. promote degradation other proteins involved normal cell growth proliferation, including MDM4 RB1. Here, we describe identification novel substrate ligase: dihydrofolate reductase (DHFR). binds directly DHFR catalyses monoubiquitination...
Introduction Inflammatory mediators play a critical role in acute pancreatitis. The precise played by members of the chemokine family remains unclear. Aims To investigate expression CC monocyte chemotactic protein (MCP)-1/JE and CXC cytokine-induced neutrophil chemoattractant (CINC) early Methodology Pancreatitis was induced rats, either intraperitoneal injection cerulein or infusion 5% sodium taurocholate into pancreatic duct. Expression MCP-1/JE CINC pancreas plasma determined...
What's known on the subject? and What does study add? Unlike most other cancers mutations of p53 gene ( TP53 ), typically indicated by increased expression, are rare in renal cell carcinomas (RCC) there is no evidence that mutation associated with outcome or treatment response. However, whilst not linked outcome, expression as we show here. Our first to demonstrate simultaneously patients (significantly MDM2 expression), have reduced disease specific survival even though expressed rarely...
Headspace-solid phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) can be used to measure volatile organic compounds (VOCs) in human urine. However, there is no widely adopted standardised protocol for the preparation of urine samples analysis resulting an inability compare studies reliably between laboratories. This paper investigated effect altering sample pH, volume, and vial size optimising detection VOCs when using HS-SPME-GC-MS. first, direct comparison H2SO4,...
Proliferative verrucous leukoplakia (PVL) is a rare form of oral with relatively high transformation rate resulting in squamous cell carcinoma (OSCC). Molecular analysis PVL at the genome level limited and has only identified molecular similarities between OSCC. However, clinical profile suggests that differences may be more important.Whole exome sequencing 5 PVL-associated OSCC (PVL-OSCC) paired blood samples was used to identify somatic mutations common tumors. Whole methylome from 4 3...
MDM2 expression, combined with increased p53 is associated reduced survival in several cancers, but particularly of interest renal cell carcinoma (RCC) where evidence suggests the presence tissue-specific p53/MDM2 pathway defects. We set out to identify MDM2-interacting proteins cells that could act as mediators/targets oncogenic effects cancers. identified non-metastatic 2, protein; NME2 (NDPK-B, NM23-B/-H2), a nucleoside diphosphate kinase, an protein using both proteomic-based strategy...
The p53 gene is the most frequently mutated in cancer and accordingly has been subject of intensive investigation for almost 30 years. Loss function due to mutations unequivocally demonstrated promote both humans model systems. As a consequence, there exists an enormous body information regarding normal biology pathobiological consequences mutation. It long recognised that analysis considerable potential as tool use diagnostic and, greater extent, prognostic settings some significant...
Abstract BACKGROUND: Recent genetic studies have implicated p53 mutation as a significant risk factor for therapeutic failure in squamous cell carcinoma of the head and neck (SCCHN). However, recent meta‐analysis literature from major anatomical subsites (larynx, oral cavity, oropharynx/hypopharynx), associations between patient survival status were ambiguous. METHODS: The authors examined cohort SCCHNs using previously developed biomarker combination that likely predicts based on p53/MDM2...
Recent studies connect MDM2 with increased cell motility, invasion and/or metastasis proposing an MDM2‐mediated ubiquitylation‐dependent mechanism. Interestingly, in renal carcinoma (RCC) p53/MDM2 co‐expression is associated reduced survival which independently linked metastasis. We therefore investigated whether expression of p53 promotes aggressive phenotypes. Our data demonstrate that motility and invasiveness RCC cells (N.B. similar results are obtained non‐RCC cells). This study shows...