A5015673151- HER2/EGFR in Cancer Research
- Occupational and environmental lung diseases
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Advanced Breast Cancer Therapies
- Bioinformatics and Genomic Networks
- Cancer Treatment and Pharmacology
- Computational Drug Discovery Methods
- Ubiquitin and proteasome pathways
- Cancer Cells and Metastasis
- Gene expression and cancer classification
- Medical Imaging Techniques and Applications
- Protein Degradation and Inhibitors
- Radiomics and Machine Learning in Medical Imaging
- Monoclonal and Polyclonal Antibodies Research
- Ferroptosis and cancer prognosis
- Single-cell and spatial transcriptomics
- Molecular Biology Techniques and Applications
- Cancer Research and Treatments
- DNA Repair Mechanisms
- Cancer Immunotherapy and Biomarkers
- Histone Deacetylase Inhibitors Research
- Metastasis and carcinoma case studies
- Sarcoma Diagnosis and Treatment
- Cell Adhesion Molecules Research
Breast Cancer Now
2020-2025
Institute of Cancer Research
2020-2025
University College London
2016-2021
CRUK Lung Cancer Centre of Excellence
2021
University College Hospital
2019
University Hospital of the West Indies
2019
Advanced Cell Diagnostics (United States)
2017
Queen's Medical Centre
2014
Cancer Research UK
2012
Queen Mary University of London
2006-2012
Abstract Patients with estrogen receptor (ER)-positive breast cancer are at risk of metastatic relapse for decades after primary tumor resection and treatment, a consequence dormant disseminated cells (DTCs) reawakening secondary sites. Here we use syngeneic ER + mouse models in which DTCs display phenotype young mice but accelerated outgrowth an aged or fibrotic microenvironment. In mice, low-level Pdgfc expression by is required their maintenance sites insufficient to support development...
Necroptosis is a lytic, inflammatory form of cell death that not only contributes to pathogen clearance but can also lead disease pathogenesis. triggered by RIPK3-mediated phosphorylation MLKL, which thought initiate MLKL oligomerisation, membrane translocation and rupture, although the precise mechanism incompletely understood. Here, we show K63-linked ubiquitin chains are attached during necroptosis ubiquitylation at K219 significantly cytotoxic potential phosphorylated MLKL. The K219R...
Abstract SF3B1 hotspot mutations are associated with a poor prognosis in several tumor types and lead to global disruption of canonical splicing. Through synthetic lethal drug screens, we identify that mutant ( MUT ) cells selectively sensitive poly (ADP-ribose) polymerase inhibitors (PARPi), independent mutation site. display defective response PARPi-induced replication stress occurs via downregulation the cyclin-dependent kinase 2 interacting protein (CINP), leading increased fork origin...
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a critical stress sentinel that coordinates cell survival, inflammation, and immunogenic death (ICD). Although the catalytic function of RIPK1 is required to trigger death, its non-catalytic scaffold mediates strong pro-survival signaling. Accordingly, cancer cells can hijack block necroptosis evade immune detection. We generated small-molecule proteolysis-targeting chimera (PROTAC) selectively degraded human murine...
Abstract Purpose: Anti-EGFR antibodies show limited response in breast cancer, partly due to activation of compensatory pathways. Furthermore, despite the clinical success cyclin-dependent kinase (CDK) 4/6 inhibitors hormone receptor–positive tumors, aggressive triple-negative cancers (TNBC) are largely resistant CDK2/cyclin E expression, whereas free CDK2 display normal tissue toxicity, limiting their therapeutic application. A cetuximab-based antibody drug conjugate (ADC) carrying a CDK...
Chordoma is a rare malignant bone tumour with poor prognosis and limited therapeutic options. We undertook focused compound screen (FCS) against 1097 compounds on three well-characterized chordoma cell lines; 154 were selected from the single concentration (1 µm), based their growth-inhibitory effect. Their half-maximal effective (EC50 ) values determined in cells normal fibroblasts. Twenty-seven of these displayed selective kill 21/27 (78%) found to be EGFR/ERBB family inhibitors. EGFR...
Dear Editor, OPSCC has one of the most rapidly increasing incidences all cancers.1-3 Most cases are associated with HPV infection, which confers improved survival outcomes, compared to HPV-independent disease.4 Despite advancements in understanding HPV-associated OPSCC, role biomarkers like B7-H3 and CEA, both HPV-positive HPV-negative remains unclear. This study addresses this gap by evaluating their expression correlations clinical immune parameters. Additionally, we developed a...
<h3>Aims</h3> To determine the role of serum and tissue IgG2 in orbital biopsies with histological features IgG4-related disease (IgG4-RD) comparison non-IgG4-related inflammatory disorders (OID), including autoimmune disorders. <h3>Methods</h3> This is an international (Sheffield, UK, Singapore) collaborative, retrospective case review 69 patients (38 from Singapore National Eye Centre 31 Royal Hallamshire Hospital, Sheffield) between 2002 2016. Clinical information histology were reviewed...
Abstract Despite increasing evidence supporting the clinical relevance of tumour infiltrating lymphocytes (TILs) in invasive breast cancer, TIL spatial variability within ductal carcinoma situ (DCIS) samples and its association with progression are not well understood. To characterise tissue architecture microenvironment DCIS, we designed validated a new deep learning pipeline, UNMaSk. Following automated detection individual DCIS ducts using method IM-Net, applied tessellation to create...
C-terminal tensin-like gene (CTEN, also known as TNS4) localizes to focal adhesions and is reported function an oncogene in colonic, breast, lung, gastric cancers. Its role pancreatic cancer unknown was thus investigated this study.C-terminal tensinlike expression evaluated by immunohistochemistry a series of Functional activity the CTEN tested manipulating cellular levels using dual approach knockdown/forced expression.The overexpressed 31 (70.45%) 44 Functionally, changes level did not...
Numerous gene signatures, or modules have been described to evaluate the immune cell composition in transcriptomes of multicellular tissue samples. However, significant diversity module content for specific types is associated with heterogeneity their performance. In order rank that best reflect purported association, we generated modular discrimination index (MDI) score assesses expression each target type relative other cells. We demonstrate MDI scores predict independently validated...
Drugs that mobilise the immune system against cancer are dramatically improving care for many people. Dying cells play an active role in inducing anti-tumour immunity but not every form of death can elicit response. Moreover, resistance to apoptosis is a major problem treatment and disease control. While term "immunogenic cell death" fully defined, activation receptor-interacting serine/threonine-protein kinase 1 (RIPK1) induce type mobilises cancer. However, no clinical protocols have yet...
Malignant mesothelioma (MM) is poorly responsive to systemic cytotoxic chemotherapy and invariably fatal. Here we describe a screen of 94 drugs in 15 exome-sequenced MM lines the discovery subset defined by loss function nuclear deubiquitinase BRCA associated protein-1 (BAP1) that demonstrate heightened sensitivity TRAIL (tumour necrosis factor-related apoptosis-inducing ligand). This association observed across human early passage cultures, mouse xenografts tumour explants. We BAP1 activity...
Trefoil factor family (TFF) peptides promote wound healing in the gut. Recent evidence has suggested that TFF3 may be a pancreatic mitogen, an unusual role for TFF peptides. We sought to clarify human and mucin expression performed vitro experiments see how cell lines respond particular.Samples of normal diseased pancreas (chronic pancreatitis, intraepithelial neoplasia, neuroendocrine tumors, ductal adenocarcinoma [PDAC]) were studied by immunohistochemistry situ hybridization. Pancreatic...
Objective The aim of this study was to explore the potential effects diet‐induced weight loss on molecular biomarkers colorectal cancer risk in serum and tissue. Methods This single‐arm exploratory included 20 adults with BMI ≥ 30 kg/m 2 completing an 8‐week, complete, low‐energy liquid diet. Pre‐ postintervention anthropometric measurements, fasting blood draws, endoscopic examinations procure biopsies were performed. Fasting insulin, glucose, insulinlike growth factor 1 (IGF‐1), C‐reactive...
Nonalcoholic fatty liver disease (NAFLD) is common among people living with HIV. There are limited data available on the pathophysiology of NAFLD and development fibrosis in this population.The aim study was to investigate association bacterial translocation, adipose tissue dysfunction, monocyte activation gut dysbiosis patients HIV monoinfection NAFLD.Cases biopsy-proven were age sex-matched HIV-positive HIV-negative controls. Markers translocation [lipopolysaccharide-binding protein (LBP),...
Abstract Mesothelioma is a universally lethal cancer lacking effective therapy. The spindle poison vinorelbine exhibits clinical activity in the relapsed setting, and preclinical models requires BRCA1 to initiate apoptosis. However, mechanisms underlying this regulation implications have not been explored. Here, we show that silencing abrogated vinorelbine-induced cell-cycle arrest, recruitment of BUBR1 kinetochores, led codepletion MAD2L1 at mRNA protein levels consistent with its status as...
Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian cancer characterised by high frequency loss-of-function
The impact of anti-tumor necrosis factor (TNF) therapies on inducible TNF-dependent activity in humans has never been evaluated vivo. We aimed to test the hypothesis that patients responding anti-TNF treatments exhibit attenuated immune responses at site an challenge. developed and validated four context-specific TNF-inducible transcriptional signatures quantify TNF bioactivity transcriptomic data. In treated rheumatoid arthritis (RA) patients, we measured expression these biosignatures...
A simple method completely removes contaminating paraffin from samples for clinical Raman and enhanced immunohistological analysis.
Triple-negative breast cancers (TNBC) are resistant to standard-of-care chemotherapy and lack known targetable driver gene alterations. Identification of novel drivers could aid the discovery new treatment strategies for this hard-to-treat patient population, yet studies using high-throughput accurate models define functions genes in TNBC date have been limited. Here, we employed unbiased functional genomics screening 200 most frequently mutated cancer, spheroid cultures model