A5103237049- Telomeres, Telomerase, and Senescence
- Effects of Radiation Exposure
- Advanced Proteomics Techniques and Applications
- Mass Spectrometry Techniques and Applications
- Genetics, Aging, and Longevity in Model Organisms
- Molecular Biology Techniques and Applications
- Mitochondrial Function and Pathology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Blood groups and transfusion
- Atrial Fibrillation Management and Outcomes
- Sports Performance and Training
- Cardiac Arrhythmias and Treatments
- Chemotherapy-induced cardiotoxicity and mitigation
- NF-κB Signaling Pathways
- Cancer Treatment and Pharmacology
- Cell death mechanisms and regulation
- Histone Deacetylase Inhibitors Research
- Radiation Therapy and Dosimetry
- Cardiac Fibrosis and Remodeling
- Viral Infections and Immunology Research
- Metabolomics and Mass Spectrometry Studies
- Chronic Lymphocytic Leukemia Research
- Motor Control and Adaptation
- Cardiac Ischemia and Reperfusion
- interferon and immune responses
Newcastle upon Tyne Hospitals NHS Foundation Trust
2024
Freeman Hospital
2024
Centre for Life
2020-2023
Newcastle University
2018-2023
University of Newcastle Australia
2018-2023
Curis (United States)
2014-2019
The Maria Sklodowska-Curie National Research Institute of Oncology
2007-2018
Inserm
2013
Université de Montpellier
2013
Institut de Recherche en Cancérologie de Montpellier
2013
à la diffusion de documents scientifiques niveau recherche, publiés ou non, émanant des établissements d'enseignement et recherche français étrangers, laboratoires publics privés.
Abstract Cardiovascular disease is the leading cause of death in individuals over 60 years old. Aging associated with an increased prevalence coronary artery and a poorer prognosis following acute myocardial infarction (MI). With age, senescent cells accumulate tissues, including heart, contribute to age‐related pathologies. However, role senescence recovery MI has not been investigated. In this study, we demonstrate that treatment aged mice senolytic drug, navitoclax, eliminates...
Abstract A key component of cardiac ischemia–reperfusion injury (IRI) is the increased generation reactive oxygen species, leading to enhanced inflammation and tissue dysfunction in patients following intervention for myocardial infarction. In this study, we hypothesized that oxidative stress, due ischemia–reperfusion, induces senescence which contributes pathophysiology IRI. We demonstrate IRI cellular both cardiomyocytes interstitial cell populations treatment with senolytic drug...
CUDC-101 is a small molecule that simultaneously inhibits the epidermal growth factor receptor (EGFR), human 2 (HER2), and histone deacetylase (HDAC) with preclinical activity in head neck squamous cell cancer (HNSCC). The primary objective of this investigation to determine maximum tolerated dose (MTD) cisplatin-radiotherapy treatment HNSCC.CUDC-101 monotherapy was administered intravenously three times weekly (Monday, Wednesday, Friday) for one-week run-in, then continued concurrent...
CUDC-101 is a novel, small-molecule, anticancer agent targeting histone deacetylase (HDAC), EGF receptor (EGFR), and HER2. It currently in phase I clinical development patients with solid tumors. Previously, we reported that has potent antiproliferative proapoptotic activity cultured tumor cells vivo xenograft models. We now show cancer have acquired resistance to single-target EGFR inhibitors through upregulation of AXL or loss E-cadherin remain sensitive CUDC-101, which inhibits MET-...
Abstract Background Mass spectrometric analysis of the blood proteome is an emerging method clinical proteomics. The approach exploiting multi-protein/peptide sets (fingerprints) detected by mass spectrometry that reflect overall features a specimen's proteome, termed pattern analysis, have been already shown in several studies to applicability cancer diagnostics. We aimed identify serum patterns specific for early stage breast patients using MALDI-ToF spectrometry. Methods Blood samples...
TPS3099 Background: Programmed-death 1 (PD-1) and V-domain Ig suppressor of T-cell activation (VISTA) are independent immune checkpoints that negatively regulate function implicated in various malignancies. Preclinical studies have demonstrated dual blockade these pathways is synergistic. CA-170 a first-in-class oral small molecule directly targets both PD-1/PD-L1 VISTA has shown anti-tumor activity multiple preclinical models. Methods: The dose escalation phase target enrollment 50 pts with...
The cellular response to ionizing radiation involves activation of p53-dependent pathways and the atypical NF-κB pathway. crosstalk between these two transcriptional networks include (co)regulation common gene targets. Here we looked for novel genes potentially (co)regulated by p53 using integrative genomics screening in human osteosarcoma U2-OS cells irradiated with a high dose (4 10 Gy). Radiation-induced expression silenced TP53 or RELA (coding p65 subunit) was analyzed RNA-Seq while...
Cardiovascular disease is recognized as an important clinical problem in radiotherapy and radiation protection. However, only few radiobiological models relevant for assessment of cardiotoxic effects ionizing are available. Here we describe the isolation mouse primary cardiac endothelial cells, a possible target radiation. Cells isolated from hearts juvenile mice were cultured irradiated vitro. In addition, cells locally adult animals (up to 6 days after irradiation) tested. A dose-dependent...
summary . Apparent deviation from Mendelian rules of blood group inheritance is rarely observed. Blood O parents with children expressing weak A subgroups have occasionally been described but not explained. detailed serological investigation such a family here. The ABO locus was analysed by PCR‐ASP/restriction fragment length polymorphism genotyping and DNA sequencing. propositus' RBCs were very weakly agglutinated monoclonal anti‐A distinctly polyclonal anti‐A,B, i.e. typical for x Serum 1...
The study aimed to detect features of human serum proteome that were associated with exposure ionizing radiation. analyzed group consisted 46 patients treated radical radiotherapy for larynx cancer; irradiated total doses in a range from 51 72 Gy. Three consecutive blood samples collected each patient: before the start, 2 weeks after and 4–6 end radiotherapy. low-molecular-weight fraction (2,000–13,000 Da) was by MALDI-ToF mass spectrometry. Proteome profiles start during early stage...
Pathways depending on the NF-κB transcription factor are essential components of cellular response to stress. Plethora stimuli modulating includes inflammatory signals, ultraviolet radiation (UV) and reactive oxygen species (ROS), yet interference between different factors affecting remains relatively understudied. Here, we aim characterize influence UV TNF-α-induced activity pathway. We document inhibition activation subsequent suppression NF-κB-regulated genes in cells exposed UV-C several...
The study aimed to investigate late radiation-induced changes in the histology, ultrastructure, and activity of lysosomal enzymes mouse liver exposed ionizing radiation. experiment was conducted on C57BL/6J male mice whose distal part occasionally single doses radiation (6 MV photons) during targeted heart irradiation; estimated delivered analyzed tissue were 0.025 Gy, 0.25 1 2 Gy. Tissues collected 40 weeks after irradiation. We have observed that effects an adaptive nature their intensity...
Chronic lymphocytic leukemia (CLL) is the most common adult in Western World and it characterized by a marked degree of clinical heterogeneity. An impaired balance between pro- anti-apoptotic stimuli determines chemorefractoriness outcome. The low proliferation rate CLL cells indicates that one primary mechanisms involved disease development may be an apoptotic failure. Here, we study functional significance DRAK2, novel stress response kinase plays critical role apoptosis, T-cell biology,...
Biological aging is associated with various morphological and functional changes, yet the mechanisms of these phenomena remain unclear in many tissues organs. Hyperlipidemia among factors putatively involved liver heart. Here, we analyzed morphological, ultrastructural, biochemical features adult (7-month-old) elderly (17-month-old) mice, then compared age-related between wild type (C57Bl/6 strain) ApoE-deficient (transgenic ApoE-/-) animals. Increased numbers damaged mitochondria,...
Improvement of radiotherapy techniques reduces the exposure normal tissues to ionizing radiation. However, risk radiation-related late effects remains elevated. In present study, we investigated long-term radiation on heart muscle morphology.We established a mouse model study microvascular density (MVD), deposition collagen fibers, and changes in accumulation heat shock 70 kDa protein 1 (HSPA1) irradiated tissue. Hearts C57BL/6 mice received single dose X‑ray range 0.2-16 Gy. Analyses were...
Chronic lymphocytic leukaemia (CLL) is a heterogeneous disease with highly variable clinical outcome. There are well-established CLL prognostic biomarkers that have transformed treatment and improved the understanding of biology. Here, we studied significance two crucial B cell regulators, BACH2 (BTB CNC homology 1, basic leucine zipper transcription factor 2) BCL6 (B-cell CLL/lymphoma 6), in cohort 102 patients determined protein interaction networks they participate using MEC-1 cells. We...
The plasma proteome was analysed as a potential source of markers radiosensitivity in patients treated with definitive radiotherapy for head and neck cancer.Acute mucosal reactions that developed during were assessed 55 patients. Blood samples collected from each patient before the treatment also 50 healthy donors. low-molecular-weight fraction (2,000-10,000 Da range) by Matrix-Assisted Laser Desorption Ionisation mass spectrometry. capacity DNA break repair comet assay using lymphocytes...
Purpose: Lysosomes may have an important role in response to ionizing radiation. Moreover, radiation could affect autophagy, which process involves the activity of lysosomal enzymes. In present study, effect on compartment mouse liver was investigated after vivo exposure.Materials and methods: Morphology ultrastructure hepatocytes were assessed by light electron microscopy, activities selected enzymes 12, 36 120 h exposure mean dose 1 Gy. The levels autophagy-related proteins LC3-II p62...