A5078841356- Colorectal Cancer Treatments and Studies
- Cell death mechanisms and regulation
- Cancer-related Molecular Pathways
- Cancer, Lipids, and Metabolism
- Genetic factors in colorectal cancer
- Pancreatic and Hepatic Oncology Research
- Cancer Research and Treatments
- Histone Deacetylase Inhibitors Research
- Prostate Cancer Treatment and Research
- Phagocytosis and Immune Regulation
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- HER2/EGFR in Cancer Research
- Lung Cancer Treatments and Mutations
- Peptidase Inhibition and Analysis
- Neuropeptides and Animal Physiology
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Cancer Treatment and Pharmacology
- Radiomics and Machine Learning in Medical Imaging
- Cancer therapeutics and mechanisms
- interferon and immune responses
- Estrogen and related hormone effects
- Cancer Mechanisms and Therapy
- Cytokine Signaling Pathways and Interactions
Queen's University Belfast
2016-2025
St Andrew's Healthcare
2021-2024
Almac (United Kingdom)
2023-2024
Heidelberg (Poland)
2023-2024
International School of Trieste
2023-2024
FC Barcelona
2023-2024
Hudson Institute
2021-2024
Cancer Research UK
2012-2022
University of Ulster
2001-2020
Indiana University School of Medicine
2020
Abstract Rewiring of host cytokine networks is a key feature inflammatory bowel diseases (IBD) such as Crohn’s disease (CD). Th1-type cytokines—IFN-γ and TNF-α—occupy critical nodes within these both are associated with disruption gut epithelial barrier function. This may be due to their ability synergistically trigger the death intestinal cells (IECs) via largely unknown mechanisms. In this study, through unbiased kinome RNAi drug repurposing screens we identified JAK1/2 kinases principal...
Abstract To elucidate mechanisms of resistance to chemotherapies currently used in the first-line treatment advanced colorectal cancer, we have developed a panel HCT116 p53 wild-type (p53+/+) and null (p53−/−) isogenic cancer cell lines resistant antimetabolite 5-fluorouracil (5-FU), topoisomerase I inhibitor irinotecan (CPT-11), DNA-damaging agent oxaliplatin. These were generated by repeated exposure stepwise increasing concentrations each drug over period several months. We demonstrated...
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...
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...
Abstract Stromal-derived intratumoural heterogeneity (ITH) has been shown to undermine molecular stratification of patients into appropriate prognostic/predictive subgroups. Here, using several clinically relevant colorectal cancer (CRC) gene expression signatures, we assessed the susceptibility these signatures confounding effects ITH microarray data obtained from multiple tumour regions a cohort 24 patients, including central tumour, invasive front and lymph node metastasis. Sample...
Abstract Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) has recently attracted attention as a potential therapeutic agent in the treatment of cancer. We assessed roles p53, TRAIL receptors, and cellular Fas-associated death domain–like interleukin-1β-converting enzyme inhibitory protein (c-FLIP) regulating cytotoxic effects recombinant (rTRAIL) alone combination with chemotherapy [5-fluorouracil (5-FU), oxaliplatin, irinotecan] panel colon cancer cell lines. Using clonogenic...
Abstract c-FLIP is an inhibitor of apoptosis mediated by the death receptors Fas, DR4, and DR5 expressed as long (c-FLIPL) short (c-FLIPS) splice forms. We found that small interfering RNA (siRNA)-mediated silencing induced spontaneous in a panel p53 wild-type, mutant, null colorectal cancer cell lines this was caspase-8 Fas-associated domain. Further analyses indicated involvement and/or Fas (but not DR4) regulating siRNA. Interestingly, these effects were dependent on activation or their...
We have shown previously that exposure to anticancer drugs can trigger the activation of human epidermal receptor survival pathways in colorectal cancer (CRC). In this study, we examined role ADAMs (a disintegrin and metalloproteinases) soluble growth factors acute drug resistance mechanism.In vitro vivo models CRC were assessed. ADAM-17 activity was measured using a fluorometric assay. Ligand shedding assessed by ELISA or Western blotting. Apoptosis flow cytometry blotting.Chemotherapy...
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...
meso-Tetra(N-methyl-4-pyridyl) porphine tetra tosylate (TMP) is a photosensitizer that can be used in photodynamic therapy (PDT) to induce cell death through generation of reactive oxygen species targeted tumor cells. However, TMP highly hydrophilic, and therefore, its ability accumulate intracellularly limited. In this study, strategy improve uptake into cells has been investigated by encapsulating the compound hydrogel-based chitosan/alginate nanoparticle formulation. Nanoparticles 560 nm...
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...
TRAIL and FasL are potent inducers of apoptosis but can also promote inflammation through assembly cytoplasmic caspase-8/FADD/RIPK1 (FADDosome) complexes, wherein caspase-8 acts as a scaffold to drive FADD/RIPK1-mediated nuclear factor κB (NF-κB) activation. cFLIP is recruited FADDosomes restricts activity apoptosis, whether regulates death receptor-initiated unclear. Here, we show that silencing or deletion leads robustly enhanced Fas-, TRAIL-, TLR3-induced inflammatory cytokine production,...