A5022855963- Sarcoma Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- Colorectal Cancer Treatments and Studies
- Gastric Cancer Management and Outcomes
- Gastrointestinal Tumor Research and Treatment
- Inflammatory mediators and NSAID effects
- Cancer, Lipids, and Metabolism
- Cancer Genomics and Diagnostics
- HER2/EGFR in Cancer Research
- Genetic factors in colorectal cancer
- Metastasis and carcinoma case studies
- Colorectal Cancer Surgical Treatments
- Lung Cancer Research Studies
- Cancer-related Molecular Pathways
- Lung Cancer Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Esophageal Cancer Research and Treatment
- Colorectal and Anal Carcinomas
- Cell death mechanisms and regulation
- Estrogen and related hormone effects
- Occupational and environmental lung diseases
- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Cancer Research and Treatments
- PI3K/AKT/mTOR signaling in cancer
Royal College of Surgeons in Ireland
2011-2023
Beaumont Hospital
2007-2018
University of Toronto
2016
St. James's Hospital
2016
Dublin City University
2016
St. Vincent's University Hospital
2016
Cancer Trials Ireland
2016
University College Dublin
2016
St James's University Hospital
2011
Botsford Hospital
2009-2011
Synthetic sickness/lethality (SSL) can be exploited to develop therapeutic strategies for cancer. Deficiencies in the tumor suppressor proteins MLH1 and MSH2 have been implicated Here we demonstrate that deficiency is SSL with inhibition of DNA polymerase POLB, whereas POLG inhibition. Both SSLs led accumulation 8-oxoG oxidative lesions. MSH2/POLB caused nuclear accumulation, MLH1/POLG a rise mitochondrial levels. were rescued by silencing adenine glycosylase MUTYH, suggesting lethality...
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 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...
Retention of abnormal α1-antitrypsin (AAT) activates the unfolded protein response in AAT-deficient monocytes. The regulatory role microRNAs (miRNAs) responses and chronic obstructive pulmonary disease pathogenesis has not been investigated.To investigate miRNA expression function MM ZZ monocytes identify miRNA(s) regulating response.Peripheral blood were isolated from asymptomatic symptomatic individuals for profiling pyrosequencing analysis. miRNA/gene was measured with quantitative...
We previously found that cellular FLICE-inhibitory protein (c-FLIP), caspase 8, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 2 (DR5) are major regulators of cell viability chemotherapy-induced apoptosis in colorectal cancer. In this study, we determined the prognostic significance c-FLIP, TRAIL DR5 expression tissues from patients with stage II III cancer.Tissue microarrays were constructed matched normal tissue derived (n = 253) enrolled a phase trial...
Transcription factors often play important roles in tumourigenesis. Members of the PEA3 subfamily ETS-domain transcription fulfil such a role and have been associated with tumour metastasis several different cancers. Moreover, activity is potentiated by Ras-ERK pathway signalling, which itself deregulated cells. Immunohistochemical patterns expression active ERK signalling were analysed mRNA levels PEA3, ER81, MMP-1 MMP-7 determined gastric adenocarcinoma samples. Here, we studied members...
Abstract Background Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with poor prognosis. inhibition induces cell death in-vitro , providing rationale for therapeutic intervention. We aimed to determine the expression profile NSCLC if it is prognostic and/or survival factor disease. Methods was examined human matched controls by western analysis...
To date, there is no uniform consensus on whether tumour regression grade (TRG) predictive of outcome in rectal cancer. Furthermore, the lack standardization TRG grading a major source variability published studies. The aim this study was to evaluate prognostic impact cohort patients with locally advanced cancer treated neoadjuvant chemoradiation therapy (CRT). In addition Mandard TRG, we utilized four systems modified from system and applied them assess which most informative.One-hundred...
Gastrointestinal stromal tumors GISTs are distinctive KIT-positive mesenchymal neoplasms. The genetic alterations leading to the malignant behavior of these not well characterized. In this study, 21 cases (eight low potential, nine primary and four intra-abdominal recurrences) were characterized by immunohistochemistry evaluated for loss heterozygosity short arm chromosome 9, using six microsatellite markers. Loss with at least one marker 9p region was a common finding in high-risk...
Novel targeted treatment of non-small cell lung cancer (NSCLC) requires accurate classification NSCLC as squamous carcinoma (SCC) and adenocarcinoma (AC). This study details the CK5/6 TTF-1 immunoprofile surgical resections 45 NSCLCs (24 ACs 21 SCCs) in tissue microarrays. All SCCs were positive, negative. 20 24 adenocarcinomas had reverse pattern. In conclusion, all this positive negative, therefore tumours that do not display phenotype are unlikely to be SCCs. is a practical panel for...
Enteric neural dysfunction leads to increased mucous production and dysmotility in inflammatory bowel disease (IBD). Prior studies have shown that tissue eosinophilia is related activity. We hypothesized interactions between eosinophils nerves contribute IBD. Tissue from patients with intractable IBD, endoscopic biopsies steroid responsive both when active quiescent, control were studied. Immunohistochemical showed localize the mucosal layer of Crohn's (CD) (p<0.001) ulcerative colitis (UC),...
Ceramide synthase 5 is involved in the de novo synthesis of ceramide, a sphingolipid cell death and proliferation. In this study, we investigated role ceramide colorectal cancer by examining expression, clinico-pathological parameters association with survival/death signalling pathways cancer. Immunohistochemical analysis CerS5 was performed on 102 samples using tissue microarrays constructed from formalin-fixed paraffin-embedded tissues. We found strong membranous staining 57 (56%) cancers....
An accurate and reproducible assay method for determining HER2 status is crucial, as a positive gene an eligibility requirement Herceptintrade mark therapy. Although immunohistochemical (IHC) assessment both practical inexpensive, worrying trend of high false-positive rates has been reported. Fluorescence in situ hybridization (FISH) the universally accepted gold standard confirming IHC 2+ cases ambiguous results but costly requires specialized equipment technical expertise. Chromogenic...
Abstract Overweight and obesity is linked to increased incidence mortality of many cancer types. Of all cancers, oesophageal adenocarcinoma (OAC) displays one the strongest epidemiological links with obesity, accounting for up 40% cases, but molecular pathways driving this association remain largely unknown. This study aimed elucidate mechanisms underpinning cancer, determine if visceral associated aggressive tumour biology in OAC. Following co‐culture adipose tissue explants, expression...
Background Changes in genomic DNA methylation associated with cancer include global hypomethylation and gene‐specific hyper‐ or hypomethylation. We have previously identified a genetic variant the MTHFR gene involved pathway which confers risk for development of squamous cell carcinoma (SCC) renal transplant patients. This has also been discovered to confer SCC nontransplant patients low folate status. Objectives To explore profile compared adjacent non‐neoplastic skin using pyrosequencing,...
Abstract BACKGROUND: Prostacyclin synthase (PGIS) metabolizes prostaglandin H(2), into prostacyclin. This study aimed to determine the expression profile of PGIS in nonsmall cell lung cancer (NSCLC) and examine potential mechanisms involved regulation. METHODS: was examined human NSCLC matched controls by reverse transcriptase polymerase chain reaction (RT‐PCR), Western analysis, immunohistochemistry. A 204‐patient tissue microarray stained for cyclooxygenase 2 (COX2) expression. Staining...
Critical to successful execution of mitochondrial-mediated apoptosis is apoptosome formation and subsequent activation caspases. Defects in this pathway have an important role colorectal carcinogenesis chemoresistance; therefore, the expression apoptosome-associated proteins may be associated with clinical outcome response chemotherapy. Here we performed a systematic analysis immunohistochemical key involved apoptosome-dependent caspase (APAF1, Pro-caspases 9 3, SMAC, XIAP) cohort Stage II...
The p16 is a tumor suppressor gene on the short arm of chromosome 9p21. product acts as negative cell cycle regulator by inhibiting G1 cyclin-dependent kinases that phosphorylate retinoblastoma protein. This study was designed to assess frequency genetic loss 9p21 and determine role pathogenesis sporadic neurofibromatosis 1 (NF1)-associated malignant peripheral nerve sheath tumors (MPNSTs). authors examined 15 cases for protein expression 10 allelic imbalance (AI)/loss heterozygosity (LOH)...
Aims Triple‐negative breast cancer ( TNBC ) is responsible for a disproportionate number of BC deaths, owing to its intrinsic aggressiveness and lack treatment options, especially targeted therapies. Thus, there an urgent need the development better treatments . Molecular alteration AKT ‐3 was previously reported in oestrogen receptor ER )‐positive has also been suggested play role hormone‐unresponsive The aim this study investigate molecular alterations , perform associated survival...
Tumor growth depends on 2 distinctive pathways: cell proliferation and apoptosis. The p53 pathway is an important regulator of the cycle as it triggers arrest or leads to apoptosis in response cellular stress therefore commonly targeted during tumorigenesis. Apoptosis also controlled by Bcl-2 family, which includes proapoptotic antiapoptotic proteins. aim this study was investigate expression proteins that are involved different types soft tissue sarcomas correlate these with histologic...