A5008650455- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Cancer Cells and Metastasis
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Lung Cancer Treatments and Mutations
- Breast Cancer Treatment Studies
- Receptor Mechanisms and Signaling
- Cardiac electrophysiology and arrhythmias
- Genomic variations and chromosomal abnormalities
- Single-cell and spatial transcriptomics
- Nicotinic Acetylcholine Receptors Study
- Pancreatic and Hepatic Oncology Research
- Molecular Biology Techniques and Applications
- Radiomics and Machine Learning in Medical Imaging
- Chemical Synthesis and Analysis
- Advanced Breast Cancer Therapies
- BRCA gene mutations in cancer
- Antimicrobial Peptides and Activities
- Neuroscience and Neural Engineering
- Amino Acid Enzymes and Metabolism
- Renal cell carcinoma treatment
- Thyroid Cancer Diagnosis and Treatment
- Computational Drug Discovery Methods
- Genetic Neurodegenerative Diseases
Leicester Royal Infirmary
2014-2024
University of Leicester
2015-2024
University College London
2002-2023
Imperial College London
2010-2019
Natera (United States)
2019
The Christie NHS Foundation Trust
2019
Cancer Research UK
2010-2016
Dartmouth College
1992-2013
Dartmouth Hospital
2013
IIT Research Institute
2012
T cell–produced cytokines play a pivotal role in the bone loss caused by inflammation, infection, and estrogen deficiency. IFN-γ is major product of activated helper cells that can function as pro- or antiresorptive cytokine, but reason why has variable effects unknown. Here we show blunts osteoclast formation through direct targeting precursors indirectly stimulates promotes resorption stimulating antigen-dependent cell activation secretion osteoclastogenic factors RANKL TNF-α. Analysis...
Up to 30% of patients with breast cancer relapse after primary treatment. There are no sensitive and reliable tests monitor these detect distant metastases before overt recurrence. Here, we demonstrate the use personalized circulating tumor DNA (ctDNA) profiling for detection recurrence in cancer.
The purpose of this study was to directly compare mutation profiles in multiple single circulating tumor cells (CTC) and cell-free DNA (cfDNA) isolated from the same blood samples taken patients with metastatic breast cancer (MBC). We aimed determine whether cfDNA would reflect heterogeneity observed 40 CTCs.
Biomarkers in breast cancer to monitor minimal residual disease have remained elusive. We hypothesized that genomic analysis of circulating free DNA (cfDNA) isolated from plasma may form the basis for a means detecting and monitoring cancer. profiled 251 genomes using Affymetrix SNP 6.0 arrays determine copy number variations (CNVs) loss heterozygosity (LOH), comparing 138 cfDNA samples with matched primary tumor normal leukocyte 65 patients eight healthy female controls. Concordance...
Circulating nucleic acids (CNAs) are under investigation as a liquid biopsy in cancer. However there is wide variation blood processing and methods for isolation of circulating free DNA (cfDNA) microRNAs (miRNAs). Here we compare the extraction efficiency reproducibility 4 commercially available kits cfDNA 3 miRNA using spike-in reference templates. We also effects increasing time between venepuncture centrifugation differential force on recovery CNAs. was quantified by TaqMan qPCR targeted...
Abstract BACKGROUND Activating mutations in the estrogen receptor 1 (ESR1) gene are acquired on treatment and can drive resistance to endocrine therapy. Because of spatial temporal limitations needle core biopsies, our goal was develop a highly sensitive, less invasive method detecting activating ESR1 via circulating cell-free DNA (cfDNA) tumor cells as “liquid biopsy.” METHODS We developed targeted 23-amplicon next-generation sequencing (NGS) panel for detection hot-spot ESR1,...
1H-Benzotriazolium 1-[bis(dimethyl-amino)methylene]-5-chloro-hexafluorophosphate (1-),3-oxide (HCTU) is a nontoxic, nonirritating and noncorrosive coupling reagent. Seven biologically active peptides (GHRP-6, (65-74)ACP, oxytocin, G-LHRH, C-peptide, hAmylin(1-37), beta-amyloid(1-42)) were synthesized with reaction times reduced to deprotection of 3 min or less 5 using HCTU as the Expensive reagents special techniques not used. Total peptide synthesis dramatically by much 42.5 h (1.8 days)...
Breast cancer tissues are heterogeneous and show diverse somatic mutations copy number alterations (CNAs). We used a novel targeted next generation sequencing (NGS) panel to examine cell-free DNA (cfDNA) detect gene amplification in women with metastatic breast (MBC).
Abstract Background Breast cancer (BC) is the most common in women, and despite introduction of new screening programmes, therapies monitoring technologies, there still a need to develop more useful tests for treatment response inform clinical decision making. The purpose this study was compare circulating cell-free DNA (cfDNA) tumour cells (CTCs) with conventional breast blood biomarkers (CA15-3 alkaline phosphatase (AP)) as predictors prognosis patients metastatic (MBC). Methods One...
SignificanceAmino acids are the building blocks of life and important signaling molecules. Despite their common structure, no universal mechanism for amino acid recognition by cellular receptors is currently known. We discovered a simple motif, which binds in various receptor proteins from all major life-forms. In humans, this motif found subunits calcium channels that implicated pain neurodevelopmental disorders. Our findings suggest γ-aminobutyric acid-derived drugs bind to same human...
PURPOSE Here, we report the sensitivity of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay (Signatera) for detection molecular relapse during long-term follow-up patients with breast cancer. METHODS A total 156 primary cancer were monitored clinically up to 12 years after surgery and adjuvant chemotherapy. Semiannual blood samples prospectively collected, analyzed retrospectively detect residual disease by ultradeep sequencing using ctDNA assays, developed from whole-exome...
The mouse mutant ducky, a model for absence epilepsy, is characterized by spike-wave seizures and cerebellar ataxia. A mutation in <i>Cacna2d2</i>, the gene encoding α2δ-2 voltage-dependent calcium channel accessory subunit, has been found to underlie ducky phenotype. mRNA strongly expressed Purkinje cells. We show that <i>du/du</i> mice have abnormalities their cell dendritic tree. results introduction of premature stop codon predicts expression truncated protein encoded first three exons...
Human epidermal growth factor receptor 2 (HER2) is amplified and overexpressed in 20–25% of breast cancers. This study investigated circulating free DNA (cfDNA) for detection HER2 gene amplification patients with cancer. Circulating was extracted from plasma unselected primary cancer (22 before surgery 68 following treatment), 30 metastatic 98 female controls using the QIAamp Blood Mini Kit (Qiagen). The ratio to an unamplified reference (contactin-associated protein 1 (CNTNAP1)) measured...
We have examined the basis for G-protein modulation of neuronal voltage-dependent calcium channels (VDCCs) α1E and α1B. A novel PCR product was isolated from rat brain. This contained an extended 5′ DNA sequence subcloned onto previously cloned isoform rbEII, giving rise to long whose N terminus by 50 amino acids. VDCC α1 subunit constructs were co-expressed with accessory α2-δ β2a subunits in Xenopus oocytes mammalian (COS-7) cells. The showed biophysical properties similar those rbEII;...
Neuronal voltage-dependent calcium channels undergo inhibitory modulation by G-protein activation, generally involving both kinetic slowing and steady-state inhibition. We have shown previously that the β-subunit of neuronal plays an important role in this process, because when it is absent, greater receptor-mediated inhibition observed (Campbell et al., 1995b). therefore hypothesized channel β-subunits normally may occlude G-protein-mediated Calcium bind to cytoplasmic loop between...
Over 30% of ERα breast cancer patients develop relapses and progress to metastatic disease despite treatment with endocrine therapies. The pioneer factor PBX1 translates epigenetic cues mediates estrogen induced binding. Here we demonstrate that plays a central role in regulating the transcriptional response epidermal growth (EGF) signaling. regulates subset EGF-ERα genes highly expressed aggressive tumours. Retrospective stratification luminal using protein levels primary further...
Abstract Breast cancer (BC) is a common in women worldwide. Despite advances treatment, up to 30% of eventually relapse and die metastatic breast cancer. Liquid biopsy analysis circulating cell-free DNA fragments the patients’ blood can monitor clonality evolving mutations as surrogate for tumour biopsy. Next generation sequencing platforms digital droplet PCR be used profile from liquid biopsies; however, they are expensive time consuming clinical use. Here, we report novel strategy with...
The mouse mutant ducky and its allele 2J represent a model for absence epilepsy characterized by spike-wave seizures cerebellar ataxia. These mice have mutations in Cacna2d2 , which encodes the α 2 δ-2 calcium channel subunit. Of relevance to ataxic phenotype, mRNA is strongly expressed Purkinje cells (PCs). du2J mutation results bp deletion coding region complete loss of protein. Here we show that du /du 30% reduction somatic current marked fall spontaneous PC firing rate at 22°C,...
// Patricia Adamo 1, * , Caroline M. Cowley Christopher P. Neal 2 Vilas Mistry 1 Karen Page Ashley R. Dennison John Isherwood Robert Hastings 3 JinLi Luo David A. Moore J. Howard Pringle L. Miguel Martins 4 Catrin Pritchard Margaret Manson and Jacqui Shaw Department of Cancer Studies, University Leicester, Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, UK Hepatobiliary Pancreatic Surgery, General Hospital, Research Centre, MRC Toxicology Unit, These authors have...
Voltage-gated calcium channel auxiliary α2δ subunits are important for trafficking and function. Here, we compare the effects of α2δ-1 an α2δ-like protein called Cachd1 on neuronal N-type (CaV2.2) channels, which in neurotransmission. Previous structural studies show VWA domain interacting with first loop CaV1.1 domain-I via its metal ion-dependent adhesion site (MIDAS) motif additional Cache interactions. has a disrupted MIDAS motif. However, increases CaV2.2 currents substantially...
Abstract: In healthy individuals, the source of cell‐free plasma DNA is predominantly apoptotic, whereas, increased integrity seen in cancer patients. Therefore, it important to carefully isolate absolutely “cell‐free” DNA. Plasma from 30 females was analyzed using 4 PCR amplicons increasing size, comparing standard blood processing with additional centrifugation steps prior extraction. Cellular contamination, indicated by positive >300 bp eliminated only after extra step. This highlights...