A5062357385- HER2/EGFR in Cancer Research
- Melanoma and MAPK Pathways
- Protein Degradation and Inhibitors
- Advanced Breast Cancer Therapies
- Breast Cancer Treatment Studies
- Metal complexes synthesis and properties
- Radiopharmaceutical Chemistry and Applications
- Cancer-related Molecular Pathways
- Chronic Lymphocytic Leukemia Research
- Monoclonal and Polyclonal Antibodies Research
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Asymmetric Hydrogenation and Catalysis
- Lung Cancer Treatments and Mutations
- Glioma Diagnosis and Treatment
- Gene expression and cancer classification
- Single-cell and spatial transcriptomics
- Breast Lesions and Carcinomas
- Molecular Biology Techniques and Applications
- Trace Elements in Health
- Cancer, Lipids, and Metabolism
- Diet and metabolism studies
- Cell Image Analysis Techniques
- Cancer Treatment and Pharmacology
- Epigenetics and DNA Methylation
Edinburgh Cancer Research
2013-2025
Western General Hospital
2007-2025
University of Edinburgh
2008-2024
Institute of Genetics and Cancer
2015-2020
UNC Lineberger Comprehensive Cancer Center
2019
University of North Carolina at Chapel Hill
2019
Wellcome Trust
2019
Institute of Molecular Genetics
2017
Ontario Institute for Cancer Research
2015
Queen's University
2015
Although the link between inflammation and cancer initiation is well established, its role in metastatic diseases, primary cause of deaths, has been poorly explored. Our previous studies identified a population metastasis-associated macrophages (MAMs) recruited to lung that promote tumor cell seeding growth. Here we show FMS-like tyrosine kinase 1 (Flt1, also known as VEGFR1) labels subset human breast cancers are significantly enriched sites. In mouse models pulmonary metastasis, MAMs...
The metabolic fate of very low density lipoprotein can be examined by following the transit its apolipoprotein B moiety through delipidation cascade, which leads to lipoprotein. In this study we have used cumulative flotation ultracentrifugation follow metabolism various subclasses that participate in process normal, hypertriglyceridemic (Type IV), and dysbetalipoproteinemic III) subjects. Large triglyceride-rich lipoproteins Svedberg units (Sf) 100-400 were converted virtually...
Aim : Immunohistochemical analysis of protein expression is central to most clinical translational studies and defines patient treatment or selection criteria for novel drugs. Interobserver variation rarely analysed despite recognition that this a key area potential inaccuracy. Therefore our aim was examine observer suggest the revision current standards. Methods results We inter‐ intra‐observer variation, by interclass correlation coefficient (ICCC) κ statistics, in 8661 samples....
The NEAT/BR9601 trial showed benefit for addition of anthracyclines to cyclophosphamide, methotrexate, and fluorouracil (CMF) as adjuvant treatment early breast cancer. We investigated prospectively predictive biomarkers anthracycline including HER2 TOP2A.
Patients with early-stage breast cancer, treated endocrine therapy, have approximately 90% 5-year disease-free survival. However, for patients at higher risk of relapse despite additional adjuvant such as chemotherapy, may be indicated. The challenge is to prospectively identify patients. Mammostrat® test uses five immunohistochemical markers stratify on tamoxifen therapy into groups inform treatment decisions. We tested the efficacy this panel in a mixed population cases single center...
Patients with early breast cancer who receive anthracycline-containing chemotherapy experience improved relapse-free (RFS) and overall survival (OS) compared those non-anthracycline-containing chemotherapy. Such benefit, however, may be restricted to women whose tumors have specific molecular characteristics. We tested the hypothesis that HER2, epidermal growth factor receptor (EGFr)/HER1, HER3, Ki67, topoisomerase IIalpha expression are predictive of outcome after anthracycline-based...
Significance Platinum-based metallodrugs are the most widely used anticancer agents. Their reduced effectiveness after repeat dosing (resistance) constitutes a major clinical problem. We study potent organo-osmium compound with improved activity over cisplatin and no cross-resistance in platinum-resistant cancers. This disrupts metabolism A2780 human ovarian cancer cells, generating reactive oxygen species damaging DNA. identified mutations complex I of electron transport chain cells suggest...
Novel pyrazolopyrimidines displaying high potency and selectivity toward SRC family kinases have been developed by combining ligand-based design phenotypic screening in an iterative manner. Compounds were derived from the promiscuous kinase inhibitor PP1 to search for analogs that could potentially target a broad spectrum of involved cancer. Phenotypic against MCF7 mammary adenocarcinoma cells generated target-agnostic structure-activity relationships biased subsequent designs breast cancer...
Abstract Purpose: The role of the type I receptor tyrosine kinase (HER) family in progression prostate cancer is controversial. Breast studies show that these receptors should be investigated as a family. current study investigates expression HER1-HER4 and EGFRvIII matched hormone-sensitive hormone-refractory tumors. Experimental Design: Immunohistochemical analysis was used to investigate protein HER1-HER4, EGFRvIII, phosphorylated Akt (pAkt) Results: Surprisingly, high HER2 membrane tumors...
The HER receptors are of therapeutic and prognostic significance in breast cancer, their function is modulated by cytoplasmic tyrosine kinases like PTK6 (brk). We performed a retrospective study on archival cancer samples from patients with long follow-up compared the protein expression between individual HERs PTK6. Univariate multivariate analyses were used to value parameters. Metastases-free survival for longer than 240 months was inversely associated (P< or =0.05) nodal status, tumour...
Abstract Background High-throughput transcriptomics has matured into a very well established and widely utilised research tool over the last two decades. Clinical datasets generated on range of different platforms continue to be deposited in public repositories provide an ever-growing, valuable resource for reanalysis. Cost tissue availability normally preclude processing samples across multiple technologies, making it challenging directly evaluate performance whether data from can reliably...
Abstract Despite the approval of several multikinase inhibitors that target SRC and overwhelming evidence role in progression resistance mechanisms many solid malignancies, inhibition its kinase activity has thus far failed to improve patient outcomes. Here we report small molecule eCF506 locks native inactive conformation, thereby inhibiting both enzymatic scaffolding functions prevent phosphorylation complex formation with partner FAK. This mechanism action resulted highly potent selective...
Aims: Membranous and cytoplasmic Ki67 immunoreactivity has recently been observed in a number of histopathological entities, but frequency occurrence relationship to prognosis more common cancers have not described. The aim was describe the pattern membranous/cytoplasmic cohort invasive breast carcinomas, their associations with grade, HER2 amplification oestrogen receptor (ER) expression. Methods results: Three hundred twenty‐two cases ductal carcinoma were assessed for histological (MIB‐1...
Transcriptomic, phenotypic and high throughput data reveal unique anticancer mechanisms shared by organometallic iridium osmium complexes.
Heterogeneity in disease mechanisms between genetically distinct patients contributes to high attrition rates late stage clinical drug development. New personalized medicine strategies aim identify predictive biomarkers which stratify most likely respond a particular therapy. However, for complex multifactorial diseases not characterized by single genetic driver, empirical approaches identifying and the promising therapies are required. In vitro pharmacogenomics seeks correlate sensitivity...
Esophageal adenocarcinoma is of increasing global concern due to incidence, a lack effective treatments, and poor prognosis. Therapeutic target discovery clinical trials have been hindered by the heterogeneity disease, “druggable” driver mutations, dominance large-scale genomic rearrangements. We previously undertaken comprehensive small-molecule phenotypic screen using high-content Cell Painting assay quantify morphological response total 19,555 small molecules across panel genetically...