A5024662956- Immune cells in cancer
- Cell Adhesion Molecules Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Chemokine receptors and signaling
- Helicobacter pylori-related gastroenterology studies
- Veterinary medicine and infectious diseases
- Advanced Breast Cancer Therapies
- PARP inhibition in cancer therapy
- Toxin Mechanisms and Immunotoxins
- Cancer Cells and Metastasis
- Management of metastatic bone disease
- COVID-19 and healthcare impacts
- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Cancer Diagnosis and Treatment
- Hepatocellular Carcinoma Treatment and Prognosis
- Sarcoma Diagnosis and Treatment
- Ovarian cancer diagnosis and treatment
- Colorectal Cancer Treatments and Studies
- Clostridium difficile and Clostridium perfringens research
- Single-cell and spatial transcriptomics
- Cardiac, Anesthesia and Surgical Outcomes
- Abdominal Trauma and Injuries
- Mast cells and histamine
- Myasthenia Gravis and Thymoma
Beatson West of Scotland Cancer Centre
2019-2024
University of Glasgow
2017-2024
Cancer Research UK Scotland Institute
2023-2024
NHS Greater Glasgow and Clyde
2020-2021
Royal Free London NHS Foundation Trust
2017
GlaxoSmithKline (United Kingdom)
2003-2013
Wellcome Trust
2003
University of Hertfordshire
1996-2001
Oxford Research Group
1994
Australian Nuclear Science and Technology Organisation
1994
ABSTRACT Genomic technologies have the potential to greatly increase efficiency of drug development process. As part our tuberculosis discovery program, we used DNA microarray technology profile drug-induced effects in Mycobacterium . Expression profiles M. treated with compounds that inhibit key metabolic pathways are required as references for assessment novel antimycobacterial agents. We studied response treatment mycolic acid biosynthesis inhibitors isoniazid, thiolactomycin, and...
X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder characterized by axonopathy and demyelination in the central nervous system adrenal insufficiency. Main X-ALD phenotypes are: (i) adult adrenomyeloneuropathy (AMN) with spinal cords, (ii) cerebral AMN brain (cAMN) (iii) a childhood variant, cALD, severe demyelination. Loss of function ABCD1 peroxisomal fatty acid transporter subsequent accumulation very-long-chain acids (VLCFAs) are common culprits to all forms X-ALD, aberrant...
Ranitidine bismuth citrate (RBC) is a new chemical entity for the treatment of peptic ulcer disease.RBC freely soluble in water (more than 600 mg/mL at pH 4.6), whereas an equimolar admixture its component molecules, and ranitidine, formed almost totally insoluble suspension. Even very low values (around 2.0), solubility ranitidine was least two-fold better admixture. Comparison several physico-chemical characteristics indicated that RBC possessed significantly different melting point...
Abstract Neutrophils are a highly heterogeneous cellular population. However, thorough examination of the different transcriptional neutrophil states between health and malignancy has not been performed. We utilized single-cell RNA sequencing human murine datasets, both publicly available independently generated, to identify transcriptomic subtypes developmental lineages in malignancy. Datasets lung, breast, colorectal cancer were integrated establish validate gene signatures. Pseudotime...
Ranitidine bismuth citrate is a novel compound formed from ranitidine and complex. In conscious dogs, had similar activity to hydrochloride as an inhibitor of histamine-induced gastric acid secretion when oral doses containing equivalent amounts base (0.1 or 0.3 mg/kg) were compared. the rat, (3-30 mg/kg p.o.) prevented mucosal damage induced by ethanol (fundic damage) indomethacin (antral damage). tripotassium dicitrato bismuthate also effective against indomethacin-induced damage, but both...
Chronic obstructive pulmonary disease (COPD) is associated with persistent inflammation and oxidative stress in susceptible individuals. Using microarray analysis of bronchial biopsy samples from patients COPD controls, we identified Wnt4 as being up-regulated COPD. Analysis showed a very strong correlation between IL8 gene expression, suggesting that plays role chronic lung inflammation. In vitro, induced proliferation human epithelial cells (BEAS-2B) normal primary concentration-dependent...
Helicobacter pylori is unique among bacterial pathogens in its ability to persist the acidic environment of human stomach. To identify H. genes responsive low pH, authors assembled a high-density array PCR-amplified random genomic DNA. Hybridization radiolabelled cDNA probes, prepared using total RNA from bacteria exposed buffer at either pH 4·0 or 7·0, allowed both qualitative and quantitative information on differential gene expression be obtained. A previously described low-pH-induced...
The aim of our study was to compare the safety and efficacy a new preparation, Dysprosium-165 Hydroxide Macro-aggregate (165Dy) with Yttrium-90 Silicate (90Y) for radiation synovectomy knee in patients RA OA. A multicentre double blind clinical trial subjects randomized receive 165Dy or 90Y undertaken Sydney, Melbourne Perth. Seventy knees 59 were studied, using as end point measurements pain on walking, at rest stiffness after rest. Cytogenetic damage, retention extra-articular spread...
The incidence of brain metastases (BM) in patients with epithelial ovarian cancer (EOC) is low: 0.3-11%. onset BM has been regarded as a late event limited treatment options and poor prognosis. This retrospective case series aims to explore the current management strategies particular emphasis on use PARP inhibitors outcomes, well identification other prognostic indicators. A total 39 were identified from eight centres UK. Clinical characteristics, details management, survival data...
This study was carried out to investigate the clinical observation that emergence of antibiotic resistance can be reduced in Helicobacter pylori if agents are administered combination with bismuth salts.Two H. isolates were grown on chocolate Columbia agar containing either ranitidine citrate (RBC) at one-half lethal concentration (8 micrograms/ml) or no drug control for 22 subcultures. After 1, 5, 8, 14, 17, and subcultures, metronidazole, clarithromycin, streptomycin calculated...
ABSTRACT Neutrophils are a highly heterogenous cellular population. However, thorough examination of the different transcriptional neutrophil states, between health and malignancy, has not been performed. We utilised single-cell RNA-sequencing human murine datasets, both publicly available independently generated, to identify transcriptomic subtypes their developmental lineages in malignancy. Datasets lung, breast colorectal cancer (CRC) were integrated establish validate reproducibility...
Niraparib, an inhibitor of poly(adenosine diphosphate [ADP]-ribose) 1 and 2, has been shown to improve progression free survival in patients when used as maintenance treatment after first-line platinum-based chemotherapy advanced stage (III IV) high-grade ovarian cancer, for relapsed disease. For grades greater than III, commonly reported side effects include bone marrow suppression (thrombocytopenia, neutropenia, anemia) hypertension. However, grade ≥ III pneumonitis was not phase trials...
Since first isolated and cultured, there have been numerous reports stating the in vitro susceptibilities of Helicobacter pylori to a wide range antibacterial agents (1,2), bismuth compounds (3), inhibiting acid secretion (4).
<p>Loss of neutrophil-specific CXCR2 attenuates suppression T-cell proliferation in neutrophils from the metastatic niche mice bearing tumors. Neutrophils liver and blood littermate either <i>Mrp8-Cre-Cxcr2<sup>+/+</sup></i> (WT) or <i>Mrp8-Cre-Cxcr2</i><sup>fl/fl</sup> (CXCR2fl) were harvested 28 days following intrasplenic injection villinCreER...
<p>Figure S8. CXCR2-lacking neutrophils from healthy mice exhibit no functional differences wild type in co-culture with KPN organoids</p>
<p>Characterization of neutrophil signatures and lineages in health PTs. <b>A,</b> Uniform Manifold Approximation Projection for Dimension (UMAP) plot healthy neutrophils grouped by tissue type. BM: bone marrow, SP: spleen, L: lung, BL: blood. <b>B,</b> UMAP plots tumor-derived type Seurat clusters (0–15). blood, L_AC: lung adenocarcinoma, KPN: colorectal cancer with <i>Kras</i>, <i>Trp53</i> Notch mutations. <b>C,</b> mouse...
<div>Abstract<p>Neutrophils are a highly heterogeneous cellular population. However, thorough examination of the different transcriptional neutrophil states between health and malignancy has not been performed. We utilized single-cell RNA sequencing human murine datasets, both publicly available independently generated, to identify transcriptomic subtypes developmental lineages in malignancy. Datasets lung, breast, colorectal cancer were integrated establish validate gene...
<p>CD4<sup>+</sup> T cells are transcriptomically altered in metastasis. <b>A</b> and <b>B,</b> UMAP plots of CD4<sup>+</sup> CD8<sup>+</sup> PT LM grouped by cell type tumor type, respectively. <b>C,</b> Differential gene expression compared with PT. <b>D</b> <b>E,</b> GO KEGG analyses metastatic cells. <b>F</b> <b>G,</b> Global cell-cell communication network the...
<p>Characterization of neutrophils in metastasis. <b>A,</b> UMAP CRCLM. <b>B,</b> Coexpression H_enriched and T_enriched signatures. One cluster is not enriched for either signature (blue arrow). <b>C</b> <b>D,</b> Unsupervised pseudotime analysis estimated smoothers TXNIP expression over the different numbered lineages. <b>E,</b> CXCR2. <b>F</b> <b>G,</b> Expression CXCL8 pseudotime....
<p>Figure S9: Summary of findings.</p>
<p>Figure S6. L-R interactions from the significant signalling pathways that mediate communication between macrophages and other immune-cell subtypes in CRCLM.</p>
<p>Figure S4. cell-cell communication networks at a signalling pathway level.</p>