- Esophageal Cancer Research and Treatment
- Cancer Immunotherapy and Biomarkers
- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Colorectal Cancer Treatments and Studies
- Gastric Cancer Management and Outcomes
- Genetic factors in colorectal cancer
- Immunotherapy and Immune Responses
- Nutrition and Health in Aging
- Angiogenesis and VEGF in Cancer
- Cancer survivorship and care
- Cancer Genomics and Diagnostics
- Inflammatory Bowel Disease
- Esophageal and GI Pathology
- Immune Cell Function and Interaction
- Ubiquitin and proteasome pathways
- Telomeres, Telomerase, and Senescence
- Clusterin in disease pathology
- Lung Cancer Treatments and Mutations
- Pancreatic and Hepatic Oncology Research
- Rheumatoid Arthritis Research and Therapies
- Nanoplatforms for cancer theranostics
- Epigenetics and DNA Methylation
- Microscopic Colitis
- Radiation Therapy and Dosimetry
St. James's Hospital
2016-2025
Trinity College Dublin
2016-2025
Cancer Institute (WIA)
2024
Royal Prince Alfred Hospital
2024
University College Dublin
1998-2019
Conway School of Landscape Design
2019
Mater Misericordiae University Hospital
2014
St. Vincent's University Hospital
2005-2013
Institute of Molecular Medicine
2012
St. Mary's Hospital
2011
This study examines the relationship between synovial hypoxia and cellular bioenergetics with inflammation.Primary rheumatoid arthritis fibroblasts (RASF) were cultured hypoxia, dimethyloxalylglycine (DMOG) or metabolic intermediates. Mitochondrial respiration, mitochondrial DNA mutations, cell invasion, cytokines, glucose lactate quantified using specific functional assays. RASF metabolism was assessed by XF24-Flux Analyzer. structural morphology transmission electron microscopy (TEM). In...
The optimum curative approach to adenocarcinoma of the oesophagus and oesophagogastric junction is unknown. We aimed compare trimodality therapy (preoperative radiotherapy with carboplatin plus paclitaxel [CROSS regimen]) contemporaneous perioperative chemotherapy regimens (epirubicin cisplatin or oxaliplatin fluorouracil capecitabine [a modified MAGIC regimen] before 2018 fluorouracil, leucovorin, oxaliplatin, docetaxel [FLOT] subsequently).
Tumor budding along the advancing front of colorectal adenocarcinoma is an early event in metastatic process. A reproducible, prognostic scoring system based on outcomes stage cancer has not been established.One hundred twenty-eight T3N0M0 carcinoma patients with known outcome were identified. was defined as isolated tumor cells or clusters <5 at invasive front. bud counts generated 5 regions 200x by 2 pathologists (conventional count method). The median per case used to divide cases into...
<h3>Introduction</h3> Hypoxia is a microenvironmental feature in the inflamed joint, which promotes survival advantage for cells. The aim of this study was to examine relationship partial oxygen pressure synovial tissue (tPO<sub>2</sub>) patients with inflammatory arthritis macroscopic/microscopic inflammation and local levels proinflammatory mediators. <h3>Methods</h3> Patients underwent full clinical assessment video arthroscopy quantify macroscopic synovitis measure tPO<sub>2</sub> under...
Current prognostic factors are poor at identifying patients risk of disease recurrence after surgery for stage II colon cancer. Here we describe a DNA microarray-based assay using clinically relevant formalin-fixed paraffin-embedded (FFPE) samples.A gene signature was developed from balanced set 73 with recurrent (high risk) and 142 no (low within 5 years surgery.The 634-probe identified high-risk hazard ratio (HR) 2.62 (P < .001) during cross validation the training set. In an independent...
Abstract Annually, ovarian cancer (OC) affects 240,000 women worldwide and is the most lethal gynecological malignancy. High‐grade serous OC (HGSOC) common aggressive subtype, characterized by widespread genome changes chromosomal instability consequently poorly responsive to chemotherapy treatment. The objective of this study was investigate role microRNA miR‐433 in cellular response cells paclitaxel We show that stable expression A2780 results induction senescence demonstrated...
Abstract Objective To assess blood vessel stability in inflammatory synovial tissue (ST) and to examine neural cell adhesion molecule (NCAM), oxidative DNA damage, hypoxia vivo. Methods Macroscopic vascularity ST oxygen levels were determined vivo patients with arthritis who undergoing arthroscopy. Vessel maturity/stability was quantified matched samples by dual immunofluorescence staining for factor VIII (FVIII)/α‐smooth muscle actin (α‐SMA). NCAM 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine...
Inflammatory mediators in the tumour microenvironment promote growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, constituents that directly influence cell maturation function are not well characterised. Our aim was to identify tumour-associated inflammatory which Tumour conditioned media obtained from cultured colorectal explant tissue contained high levels chemokines CCL2, CXCL1, CXCL5 addition VEGF....
Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within HLA region) and 16q23, where closest protein-coding gene is FOXF1. Subsequently, Esophageal Adenocarcinoma Consortium (BEACON) identified loci for near CRTC1 BARX1, within 100 kb FOXP1. aimed identify further SNPs that increased validate previously reported associations.
Increasing levels of tissue hypoxia have been reported as a natural feature the aging prostate gland and may be risk factor for development cancer. In this study, we used PwR-1E benign epithelial cells an equivalently aged hypoxia-adapted sub-line to identify phenotypic epigenetic consequences chronic in cells. We identified significantly altered cellular phenotype response characterized by increased receptor-mediated apoptotic resistance, induction senescence, invasion secretion IL-1β, IL6,...
To assess levels of oxidative DNA damage (8-oxo-7,8-dihydro-2'-deoxyguanine; 8-oxo-dG) and lipid peroxidation (4-hydroxy-2-nonenal; 4-HNE) in serum, synovial fluid tissue patients with inflammatory arthritis relation to vivo hypoxia levels, disease activity angiogenic markers.Oxygen were assessed using an oxygen/temperature probe. Nuclear cytoplasmic 8-oxo-dG 4-HNE from 23 by immunohistochemistry. 8-Oxo-dG serum determined hexanoyl-Lys (HEL) adduct ELISAs, respectively. Serum vascular...
To assess the levels and spectrum of mitochondrial DNA (mtDNA) point mutations in synovial tissue from patients with inflammatory arthritis relation to vivo hypoxia oxidative stress levels.Random Mutation Capture assay was used quantitatively evaluate alterations genome. In oxygen (tPO(2)) were measured at arthroscopy using a Licox probe. Synovial expression lipid peroxidation (4-hydroxynonenal [4-HNE]) cytochrome c oxidase subunit II (CytcO II) deficiency assessed by immunohistochemistry....
Neoadjuvant chemoradiation therapy (CRT) is increasingly the standard of care for locally advanced oesophageal cancer. A complete pathological response to CRT associated with a favourable outcome. Radiation important local tumour control, however, radioresistance remains substantial clinical problem. We hypothesise that alterations in mitochondrial function and energy metabolism are involved adenocarcinoma (OAC). To investigate this, we used an established isogenic cell line model...
Genome instability is regarded as a hallmark of cancer. Human tumors frequently carry clonally expanded mutations in their mitochondrial DNA (mtDNA), some which may drive cancer progression and metastasis. The high prevalence clonal tumor mtDNA has commonly led to the assumption that genome genetically unstable, yet this hypothesis not been experimentally tested. In study, we directly measured frequency non-clonal (random) de novo single base substitutions human colorectal cancers....
<h3>Background</h3> To examine the association between mitochondrial mutagenesis and proinflammatory microenvironment in patients with inflammatory arthritis. <h3>Methods</h3> Fifty arthritis underwent arthroscopy synovial tissue biopsies, fluid clinical assessment were obtained. Fifteen pre/post-TNFi therapy also recruited. Normal biopsies obtained from 10 subjects undergoing interventional arthroscopy. Macroscopic synovitis/vascularity was measured by visual analogue scale. Cell-specific...
Objective: The Rehabilitation Strategies in Esophagogastric cancer (RESTORE) randomized controlled trial evaluated the efficacy of a 12-week multidisciplinary program to increase cardiorespiratory fitness and health-related quality life (HRQOL) esophagogastric survivors. Background: Patients following treatment for are at risk physical deconditioning, nutritional compromise, sarcopenia. Accordingly, compelling rationale exists target these impairments recovery. Methods: Disease-free patients...