- Pancreatic and Hepatic Oncology Research
- Phagocytosis and Immune Regulation
- Axon Guidance and Neuronal Signaling
- Esophageal Cancer Research and Treatment
- Gastric Cancer Management and Outcomes
- Colorectal Cancer Treatments and Studies
- Genetic factors in colorectal cancer
- Cancer, Lipids, and Metabolism
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Angiogenesis and VEGF in Cancer
- Cancer Research and Treatments
- Neuroendocrine Tumor Research Advances
- Pancreatitis Pathology and Treatment
- Epigenetics and DNA Methylation
- Signaling Pathways in Disease
- Lung Cancer Treatments and Mutations
- Liver physiology and pathology
- Eosinophilic Esophagitis
- Sarcoma Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Occupational and environmental lung diseases
- Gastrointestinal Tumor Research and Treatment
- Cell death mechanisms and regulation
- Bladder and Urothelial Cancer Treatments
Queen's University Belfast
2005-2019
National Health Service
2018
Belfast Health and Social Care Trust
2013-2017
Royal Victoria Hospital
1996-2017
University of Ulster
1993-2017
University of Birmingham
2015
University College London
2015
Queen Mary University of London
2015
National University Health System
2013
National University of Singapore
2013
Abstract Purpose: A number of independent gene expression profiling studies have identified transcriptional subtypes in colorectal cancer with potential diagnostic utility, culminating publication a Consensus Molecular Subtype classification. The worst prognostic subtype has been defined by genes associated stem-like biology. Recently, it shown that the majority this poor group are stromal derived. We investigated for tumor misclassification into multiple subgroups based on tumoral region...
EphA2, a member of the Eph receptor tyrosine kinases family, is an important regulator tumor initiation, neovascularization, and metastasis in wide range epithelial mesenchymal cancers; however, its role colorectal cancer recurrence progression unclear.EphA2 expression was determined by immunohistochemistry stage II/III tumors (N = 338), findings correlated with clinical outcome. The correlation between EphA2 stem cell markers CD44 Lgr5 examined. migration/invasion assessed using panel KRAS...
Despite the use of 5-fluorouracil (5-FU)-based adjuvant treatments, a large proportion patients with high-risk stage II/III colorectal cancer will relapse. Thus, novel therapeutic strategies are needed for early-stage cancer. Residual micrometastatic disease from primary tumor is major cause patient
A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, investigations such alterations, including changes chromatin proteins histone modifications, have potential to lead therapeutic reversion. We report here that transformed HPV16 E6/E7-expressing primary foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression PRC2 methyltransferase EZH2 at mRNA protein levels but do not exhibit...
RALA is a novel 30 mer bioinspired amphipathic peptide that showing promise for gene delivery. Here, we used to deliver the FK506-binding protein like - FKBPL (pFKBPL) member of immunophilin family. secreted protein, with overexpression shown inhibit angiogenesis, tumor growth and stemness, through variety intra- extracellular signaling mechanisms. We also elucidated proangiogenic activity stemness after utilizing siRNA (siFKBPL).The RALA/pFKBPL RALA/siFKBPL nanoparticles were characterized...
Transcriptomic profiling of colorectal cancer (CRC) has led to identification four consensus molecular subtypes (CMS1-4), which have prognostic value in stage II/III disease. More recently, the Colorectal Cancer Intrinsic Subtypes (CRIS) classification system helped define biology specific epithelial component tumors. However, clinical these classifications predicting response standard-of-care adjuvant chemotherapy remains unknown.Using samples from 4 European sites, we assembled a novel CRC...
OBJECTIVES: The association between aspirin use and improved survival after colorectal cancer diagnosis may be more pronounced in tumors that have PIK3CA mutations or high PTGS2 expression. However, the evidence of a difference by biomarker status lacks consistency. In this population-based colon cohort study interaction these biomarkers, use, was assessed. METHODS: consisted 740 stage II III patients diagnosed 2004 2008. Aspirin determined through clinical note review. Tissue blocks were...
Organotypic models may provide mechanistic insight into colorectal cancer (CRC) morphology. Three-dimensional (3D) gland formation is regulated by phosphatase and tensin homologue deleted on chromosome 10 (PTEN) coupling of cell division cycle 42 (cdc42) to atypical protein kinase C (aPKC). This study investigated PTEN phosphatase-dependent phosphatase-independent morphogenic functions in 3D assessed translational relevance human studies. Isogenic PTEN-expressing or PTEN-deficient cultures...
The antitumor effects of FK506-binding protein like (FKBPL) and its extracellular role in angiogenesis are well characterized; however, physiological/developmental the effect FKBPL ablation has not been evaluated. This is important as some angiogenic proteins dosage dependent. Here we evaluate regulation secretion under stimuli, using mouse zebrafish models. secreted maximally by human microvascular endothelial cells fibroblasts, this was specifically downregulated proangiogenic hypoxic...
USP17 is a cell cycle regulated deubiquitinating enzyme that highly expressed in tumor-derived lines and has an established role proliferation chemotaxis. This the first study to examine clinical significance of expression non-small lung cancer (NSCLC). was overexpressed both squamous adenocarcinoma NSCLC tissue. Patients with positive tumors had significantly reduced recurrence-free survival than patients negative tumors. Moreover, more recurrence disease at distant sites, suggesting levels...
Statin use after colorectal cancer diagnosis may improve survival but evidence from observational studies is conflicting. The anti-cancer effect of statins be restricted to certain molecular subgroups. In this population-based cohort study, the interaction between p53 and 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGCR) expression, KRAS mutations, association statin colon was assessed. consisted 740 stage II III patients diagnosed 2004 2008. determined through clinical note review....
Evasion of apoptosis contributes to both tumourigenesis and drug resistance in non-small cell lung carcinoma (NSCLC). The pro-apoptotic BCL-2 family proteins BAX BAK are critical regulators mitochondrial apoptosis. New strategies for targeting NSCLC a mitochondria-independent manner should bypass this common mechanism block. BRCA1 mutation frequency cancer is low; however, decreased mRNA protein expression levels have been reported significant proportion adenocarcinomas. mutation/deficiency...
Therapeutic options for malignant pleural mesothelioma (MPM) are limited despite the increasing incidence globally. The vinca alkaloid vinorelbine exhibits clinical activity; however, to date, treatment optimization has not been achieved using biomarkers. BRCA1 regulates sensitivity microtubule poisons; its role in regulating vinorelbine-induced apoptosis is unknown. Here we demonstrate that plays an essential mediating apoptosis, as evidenced by (1) strong correlation between and expression...
Objective Current strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability a DNA damage immune response (DDIR) assay predict following chemotherapy OAC. Design Transcriptional profiling 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed. All patients were treated with platinum-based and resection between 2003 2014 at four centres Oesophageal Cancer Clinical Molecular Stratification...
Primary synovial chondromatosis (PSC) is thought to be a cartilaginous metaplasia, but it may recur locally and malignant change has been reported. Histologically, the cartilage usually cellular, with binucleate forms. These findings suggest that disease not simply metaplasia imply proliferative component. In this study, immunohistochemical detection of Ki-67 protein using an antigen retrieval microwave heating technique DNA image cytometry (VIDAS analysis system) used assess activity in 20...
Testicular Leydig cell tumours are rare. Although most behave benignly approximately 10% malignant. Clinicopathological features have been described which some value in predicting malignant behaviour, although as with other endocrine uncertainties remain many individual cases. Our aim was to determine the clinicopathological of 20 testicular tumours. We wished investigate whether, addition established features, MIB1 index and/or flow cytometric analysis nuclear DNA content malignancy. also...
Based on promising preclinical efficacy associated with the 20S proteasome inhibitor bortezomib in malignant pleural mesothelioma (MPM), two phase II clinical trials have been initiated (EORTC 08052 and ICORG 05–10). However, potential mechanisms underlying resistance to this targeted drug MPM are still unknown. Functional genetic analyses were conducted determine key mitochondrial apoptotic regulators required for sensitivity establish how their dysregulation may confer resistance. The...
// Jaine K. Blayney 1, * , Lauren Cairns Gerald Li 1 Niamh McCabe Leanne Stevenson Christopher J. Peters 2 Nathan B. Reid Veronica Spence Chintapuza Chisambo Damian McManus 3 Jacqueline James Stephen McQuaid Stephanie Craig Kenneth Arthur Darragh McArt Chin-Ann Ong 4 Pierre Lao-Sirieix Peter Hamilton Manuel Salto-Tellez Martin Eatock 5 Helen G. Coleman 6 Rebecca C. Fitzgerald Richard D. Kennedy Turkington On behalf of the Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS)...
Histone acetylation is a fundamental mechanism in the regulation of local chromatin conformation and gene expression. Research has focused on impact altered epigenetic environments expression specific genes their pathways. However, changes histone also have global cell. In this study we used digital texture analysis to assess patterns following treatment with trichostatin A (TSA) observed significant alterations condensation distribution higher-order chromatin, which were associated profiles...