A5007473858- Occupational and environmental lung diseases
- Cancer Research and Treatments
- Genetic factors in colorectal cancer
- Viral gastroenteritis research and epidemiology
- Redox biology and oxidative stress
- Animal Virus Infections Studies
- Pancreatic and Hepatic Oncology Research
- Hepatitis B Virus Studies
- Pleural and Pulmonary Diseases
- Cancer Genomics and Diagnostics
- Carcinogens and Genotoxicity Assessment
- Virus-based gene therapy research
- DNA Repair Mechanisms
- Synthesis and Characterization of Heterocyclic Compounds
- Viral Infections and Outbreaks Research
- Rabbits: Nutrition, Reproduction, Health
- Ferroptosis and cancer prognosis
- Lymphatic System and Diseases
- Lymphatic Disorders and Treatments
- Animal health and immunology
- Heme Oxygenase-1 and Carbon Monoxide
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cannabis and Cannabinoid Research
- Parasitic Infections and Diagnostics
- Glutathione Transferases and Polymorphisms
University of Leicester
2019-2025
National Institute for Health Research
2024
Cancer Research UK
2024
University Hospitals of Leicester NHS Trust
2024
University of Szczecin
2010-2015
Abstract Malignant Pleural Mesothelioma (MPM) is typically diagnosed 20–50 years after exposure to asbestos and evolves along an unknown evolutionary trajectory. To elucidate this path, we conducted multi-regional exome sequencing of 90 tumour samples from 22 MPMs acquired at surgery. Here show that exomic intratumour heterogeneity varies widely across the cohort. Phylogenetic tree topology ranges linear highly branched, reflecting a steep gradient genomic instability. Using transfer...
Malignant pleural effusion (MPE) is the buildup of fluid, cellular material, cytokines, and excreted proteins in space due to tumor burden. Approximately 90% mesothelioma (PM) patients 20% all advanced cancer will present with an MPE. The composition MPE has been shown be predicative burden response therapy. In ongoing MITOPE phase 1/2 clinical trial, RSO-021 being tested for efficacy arising from or other metastatic tumors lung (NCT05278975). Results Phase 1 trial showed promise that this...
Abstract Tumor cells generate increased levels of reactive oxygen species (ROS) that promote tumor cell growth. To survive under elevated ROS levels, must increase antioxidant expression, activity, and reliance on scavenging pathways, including the mitochondrial matrix hydrogen peroxide (H2O2) enzyme peroxiredoxin 3 (PRX3). PRX3 expression is in many cancers, mesothelioma, associated with proliferation, resistance to apoptosis chemotherapy. a novel molecular target first-in-human covalent...
Abstract Background: Mesothelioma is a lethal cancer caused by asbestos. Effective therapy in the relapsed setting, following standard of care treatments lacking [1]. Inhibition Poly-ADP ribose polymerase (PARPi) mediates synthetic lethality cancers harboring DNA damage response gene (DDR) inactivation, notably BRCA1/2 resulting homologous recombination deficiency (HRD), and transcription replication conflicts (TRCs). In mesothelioma PARPi was clinically active MIST1 phase II trial [2],...
Abstract Malignant mesothelioma is a rare tumour caused by asbestos exposure that originates mainly from the pleural lining or peritoneum. Treatment options are limited, and prognosis dismal. Although immune checkpoint blockade (ICB) can improve survival outcomes, determinants of responsiveness remain elusive. Here, we report outcomes multi-centre phase II clinical trial (MiST4, NCT03654833) evaluating atezolizumab bevacizumab (AtzBev) in patients with relapsed mesothelioma. We also use...
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...
The pathogenicity of RHDV (rabbit haemorrhagic disease virus) is mainly associated with its affinity to blood vessels, causing disseminated intravascular coagulations (DIC), and the stimulation host immune system. Moreover, there are implications suggesting that apoptosis may be a pivotal process in understanding basis viral rabbits - serious infectious mortality wild domestic rabbits. aim this study evaluate, by means flow cytometry, dynamics peripheral granulocytes lymphocytes...
Abstract The tumour suppressor BRCA1-associated protein 1 (BAP1) is the most frequently mutated cancer gene in mesothelioma. Here we report novel functions for BAP1 mitotic progression highlighting relationship between and control of genome stability mesothelioma cells with therapeutic implications. Depletion induced proteasome-mediated degradation BRCA1 while loss correlated patient samples. also led to defects that phenocopied including spindle assembly checkpoint failure, centrosome...
8506 Background: Leveraging adaptive immunity to control mesothelioma is now a standard approach, however the factors that underpin clinical response are poorly understood. Here we report final analysis of CONFIRM trial (NCT03063450), double-blind phase III randomized study PD-1 inhibitor nivolumab (N) versus placebo (P) in patients (pts) with unresectable mesothelioma. Genomic, transcriptomic and multiplex spatial phenotypic correlates were explored mesotheliomas exhibiting either partial...
Malignant pleural mesothelioma (MPM), a rare cancer long latency period (up to 40 years) between asbestos exposure and disease presentation. The mechanisms coupling recurrent somatic alterations are poorly defined. Gene fusions arising through genomic instability may create novel drivers during early MPM evolution. We explored the gene that occurred in evolutionary history of tumor. conducted multiregional whole exome sequencing (WES) 106 samples from 20 patients undergoing pleurectomy...
Abstract The paper concerns the use of a novel, very effective diagnostic method, real-time PCR for diagnosis viral agent causing haemorrhagic disease in rabbits - RHDV. Until now, method was widely used detecting many different viruses, both DNA, and RNA, but as far RHDV is concerned, there are not records such use. This study aimed at detection 17 strains from European regions, differing biological features mortality. confirmed that an applicable RHDV, irrespective stains’ features.
AMA Niedźwiedzka-Rystwej P, Tokarz-Deptuła B, Hukowska-Szematowicz Działo J, Deptuła W. Research paperIndices of non-specific immunity: an element natural immunity in rabbits infected with RHD (rabbit haemorrhagic disease) virus. Central European Journal Immunology. 2013;38(2):231-236. doi:10.5114/ceji.2013.35039. APA Niedźwiedzka-Rystwej, P., Tokarz-Deptuła, B., Hukowska-Szematowicz, Działo, J., & Deptuła, (2013). Immunology, 38(2), 231-236. https://doi.org/10.5114/ceji.2013.35039 Chicago...
Abstract Mesothelioma, a lethal cancer associated with asbestos exposure, lacks effective drug therapy particularly in the relapsed treatment setting. Epithelial-to-mesenchymal transition (EMT) confers an aggressive sarcomatoid phenotype capable of invasion, metastasis, and resistance. Pharmacological targeting EMT could favorably alter progression mesothelioma. We identified geospatial transcriptomic gradient between adjacent epithelioid regions patient-derived biphasic mesotheliomas...
Abstract Mitochondrial peroxiredoxin 3 (PRX3) has been identified as an actionable cancer vulnerability that is currently being investigated in the first-in-human phase 1 clinical trial, MITOPE (NCT05278975). RSO-021 (thiostrepton or TS) a redox-active drug inhibits PRX3’s peroxidase activity via covalent adduction of its active site peroxidatic and resolving cysteine residues, forming irreversible crosslink across protein dimer. Covalent inhibition PRX3 results tumor cell death due to...
Abstract Mesothelioma is a universally lethal, rare cancer caused by asbestos that lacking effective targeted treatments, particularly in the relapsed setting. P53 predominantly wildtype (WT 83%) but likely restrained MDM2 context of 9p21 deletion, common, clonal somatic event affecting around half all mesotheliomas results deletion suppressor ARF. also associated with cold, immunosuppressed microenvironment. Unleashing p53WT inhibiting its interaction has therapeutic potential mesothelioma....