A5033442365- Pancreatic and Hepatic Oncology Research
- Phagocytosis and Immune Regulation
- Axon Guidance and Neuronal Signaling
- Esophageal Cancer Research and Treatment
- Cancer Genomics and Diagnostics
- Bioinformatics and Genomic Networks
- Gastric Cancer Management and Outcomes
- Gene expression and cancer classification
- Molecular Biology Techniques and Applications
- Prostate Cancer Treatment and Research
- Colorectal Cancer Treatments and Studies
- Cancer Immunotherapy and Biomarkers
- Genetic factors in colorectal cancer
- Microbial Metabolic Engineering and Bioproduction
- Pancreatitis Pathology and Treatment
- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
- Computational Drug Discovery Methods
- Prostate Cancer Diagnosis and Treatment
- Glycosylation and Glycoproteins Research
- Cytokine Signaling Pathways and Interactions
- Acute Myeloid Leukemia Research
- Angiogenesis and VEGF in Cancer
- Protein Degradation and Inhibitors
- Genomics and Rare Diseases
Queen's University Belfast
2015-2024
Queens University
2022
Altnagelvin Area Hospital
2015
University of Ulster
2009-2015
Ludwig Boltzmann Institute for Cancer Research
2015
Medical University of Vienna
2015
National University Cancer Institute, Singapore
2013
National University of Singapore
2013
Mayo Clinic
2011
Almac (United Kingdom)
2011
Abstract Prostate cancer (PCa) is the most prevalent in men. Hyperactive STAT3 thought to be oncogenic PCa. However, targeting of IL-6/STAT3 axis PCa patients has failed provide therapeutic benefit. Here we show that genetic inactivation Stat3 or IL-6 signalling a Pten -deficient mouse model accelerates progression leading metastasis. Mechanistically, identify p19 ARF as direct target. Loss disrupts ARF–Mdm2–p53 tumour suppressor bypassing senescence. Strikingly, also and CDKN2A mutations...
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
There are currently no approved targeted therapies for advanced KRAS mutant (KRASMT) colorectal cancer (CRC).Using a unique systems biology approach, we identified JAK1/2-dependent activation of STAT3 as the key mediator resistance to MEK inhibitors in KRASMT CRC vitro and vivo.Further analyses acute increases c-MET activity following treatment with models, which was demonstrated promote JAK1/ 2-STAT3-mediated resistance.Furthermore, inhibition found be due ERK-dependent metalloprotease...
The discovery of underlying mechanisms drug resistance, and the development novel agents to target these pathways, is a priority for patients with advanced colorectal cancer (CRC). We previously undertook systems biology approach design functional genomic screen identified fibroblast growth factor receptor 4 (FGFR4) as potential mediator resistance. aim this study was examine role FGFR4 in resistance using RNAi small-molecule inhibitor BGJ398 (Novartis). found that highly expressed at RNA...
In recent years there has been rising interest in the field of protein–protein conjugation, especially related to bispecific antibodies (bsAbs) and their therapeutic applications. These constructs contain two paratopes capable binding distinct epitopes on target molecules are thus able perform complex biological functions (mechanisms action) not available monospecific mAbs. Traditionally these bsAbs have constructed through protein engineering, but recently chemical methods for construction...
The role of PD-L1 as a prognostic and predictive biomarker is an area great interest. However, there lack consensus on how to deliver clinical biomarker. At the heart this conundrum subjective scoring IHC in most studies date. Current standard systems involve separation epithelial inflammatory cells find significance different percentages expression, e.g., above or below 1%. Clearly, objective, reproducible accurate approach would bring degree necessary consistency landscape. Using...
Here, we show for the first time, that familial breast/ovarian cancer susceptibility gene BRCA1 activates Notch pathway in breast cells by transcriptional upregulation of ligands and receptors both normal cells. We demonstrate through chromatin immunoprecipitation assays is localized to a conserved intronic enhancer region within ligand Jagged-1 (JAG1) gene, an event requiring ΔNp63. propose this BRCA1/ΔNp63-mediated induction JAG1 may be important regulation stem/precursor cells, as...
A role for BRCA1 in the direct and indirect regulation of transcription is well established. However, a comprehensive view degree to which impacts transcriptional on genome-wide level has not been defined. We performed expression profiling ChIP-chip analysis, comparison revealed that although depletion results changes 1294 genes, only 44 these are promoter bound by BRCA1. 27% transcripts were linked possibly explaining large number observed microarray analysis. show no specific consensus...
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...
Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy.To identify a molecular subgroup cancers metastatic potential at presentation resulting in high risk prostatectomy.Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 lymph nodes, and 25 normal samples. Independent assay validation 322 prostatectomy samples four sites mean follow-up 50.3 months.Molecular subgroups were...
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...
Here, we describe gene expression compositional assignment (GECA), a powerful, yet simple method based on statistics that can validate the transfer of prior knowledge, such as lists, into independent data sets, platforms and technologies. Transcriptional profiling has been used to derive lists stratify patients prognostic molecular subgroups assess biomarker performance in pre-clinical setting. Archived public sets are an invaluable resource for subsequent silico validation, though their use...
The advent of next generation sequencing technologies (NGS) has expanded the area genomic research, offering high coverage and increased sensitivity over older microarray platforms. Although current cost is still exceeding that approaches, rapid advances in NGS will likely make it platform choice for future research differential gene expression. Connectivity mapping a procedure examining connections among diseases, genes drugs by expression initially based on technology, with which large...
Objectives. Patients with celiac disease (CD) are at increased risk of osteoporosis and compromised B-vitamin status. Emerging evidence supports a beneficial role folate the metabolically related B-vitamins in bone health generally healthy adults, but no previous study has investigated this CD patients. The aim current was to examine relationship folate, vitamins B12, B6 B2 (riboflavin), metabolite homocysteine, mineral density (BMD) Materials methods. Of 400 treated adult patients invited...
Modern cancer research on prognostic and predictive biomarkers demands the integration of established emerging high‐throughput technologies. However, these data are meaningless unless carefully integrated with patient clinical outcome epidemiological information. Integrated datasets hold key to discovering new therapeutic targets in cancer. We have developed a novel approach set methods for integrating interrogating phenomic, genomic sets facilitate biomarker discovery stratification....
// 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)...
Abstract Paediatric acute myeloid leukaemia (AML) is a heterogeneous disease characterised by genetics and morphology. The introduction of intensive chemotherapy treatments together with patient stratification supportive therapy has resulted in moderate improvement prognosis. However, overall survival rates remain unacceptably poor, only 65% patients surviving longer than 5 years. Recently age-specific differences AML have been identified, highlighting the need for tailored paediatric...
Paediatric acute myeloid leukaemia (AML) continues to present treatment challenges, as no "standard approach" exists treat those young patients reliably and safely. Combination therapies could become a viable option for treating with AML, allowing multiple pathways be targeted. Our in silico analysis of AML highlighted "cell death survival" an aberrant, potentially targetable pathway paediatric patients. Therefore, we aimed identify novel combination target apoptosis. apoptotic drug...