A5026843001- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Renal and related cancers
- RNA modifications and cancer
- Renal cell carcinoma treatment
- Cancer-related gene regulation
- Cystic Fibrosis Research Advances
- Sulfur Compounds in Biology
- Hepatitis C virus research
- Brain Metastases and Treatment
- HIV/AIDS drug development and treatment
- Peroxisome Proliferator-Activated Receptors
- Glioma Diagnosis and Treatment
- Autophagy in Disease and Therapy
- Adrenal and Paraganglionic Tumors
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer Genomics and Diagnostics
- MicroRNA in disease regulation
- Cancer-related Molecular Pathways
- Histone Deacetylase Inhibitors Research
- Sarcoma Diagnosis and Treatment
- Pancreatic function and diabetes
- Biochemical and Molecular Research
- Alcohol Consumption and Health Effects
- Neonatal Respiratory Health Research
University of Wolverhampton
2013-2024
Vertex Pharmaceuticals (United States)
2013-2021
Sunshine Coast University Hospital
2020
Brain Tumour Research
2016
University of Birmingham
2005-2015
Cancer Research UK Clinical Trials Unit
2010-2012
Merck & Co., Inc., Rahway, NJ, USA (United States)
2011
Cancer Research UK
2005-2010
University of Wales
1998-2008
Molecular Oncology (United States)
2004-2008
Familial renal cell carcinoma (RCC) is a heterogeneous disorder that most commonly caused by germline mutations in the VHL , MET and FLCN genes or constitutional chromosome 3 translocations. However, for many patients with familial RCC, genetic basis of disease undefined. We investigated whether fumarate hydratase ( FH ) succinate dehydrogenase subunit SDHB SDHC SDHD were associated RCC susceptibility 68 no clinical evidence an syndrome. No identified probands, but (4.4%) probands had...
The histiocytoses are a heterogeneous group of disorders characterised by an excessive number histiocytes. In most cases the pathophysiology is unclear and treatment nonspecific. Faisalabad histiocytosis (FHC) (MIM 602782) has been classed as autosomal recessively inherited form with similarities to Rosai-Dorfman disease (RDD) (also known sinus massive lymphadenopathy (SHML)). To elucidate molecular basis FHC, we performed autozygosity mapping studies in large consanguineous family...
Glioblastoma (GBM) is the most common and malignant type of primary brain tumor in adults prognosis GBM patients poor. However, a small percentage show long term survival 36 mo or longer after diagnosis. Epigenetic profiles can provide molecular markers for patient prognosis: recently, G-CIMP positive phenotype associated with IDH1 mutations has been described GBMs good prognosis. In present analysis we performed genome-wide DNA methylation profiling short-term survivors (STS; overall < 1 y)...
Abstract Following treatment with a demethylating agent, 5 of 11 renal cell carcinoma (RCC) lines showed increased expression hepatocyte growth factor (HGF) activator inhibitor type 2 (HAI-2/SPINT2/Bikunin), Kunitz-type protease that regulates HGF activity. As activating mutations in the MET proto-oncogene (the receptor) cause familial RCC, we investigated whether HAI-2/SPINT2 might act as RCC tumor suppressor gene. We found transcriptional silencing HAI-2 was associated promoter region...
Patients with sepsis commonly develop leukocytosis, which is presumed to reflect a host response infection. Effective phagocytosis by neutrophils crucial in the clearance of invading microbes. However, efficacy controversial. We hypothesized that phagocytic capacity can be affected immature are released into circulation. Circulating were evaluated 16 patients severe and 5 healthy donors. Immature identified cell morphology. Phagocytosis was micromanipulation technique simultaneous...
Familial renal cell carcinoma (RCC) is genetically heterogeneous and may be caused by mutations in multiple genes, including VHL, MET, SDHB, FH, FLCN, PTEN, BAP1. However, most individuals with inherited RCC do not have a detectable germline mutation. To identify novel we undertook exome resequencing studies familial kindred identified CDKN2B nonsense mutation that segregated status. Targeted of (n = 82) features then revealed three candidate missense (p.Pro40Thr, p.Ala23Glu, p.Asp86Asn). In...
Tumour metastasis to the brain is a common and deadly development in certain cancers; 18–30 % of breast tumours metastasise brain. The contribution that gene silencing through epigenetic mechanisms plays these metastatic not well understood. We have carried out bioinformatic screen genome-wide tumour methylation data available at Cancer Genome Atlas (TCGA) broad literature review identify candidate genes may contribute (BBM). This analysis identified 82 candidates. investigated status using...
It is common practice to freeze dry probiotic bacteria improve their shelf life. However, the drying process itself can be detrimental viability. The viability of probiotics could maintained if they are administered within a microbially produced biodegradable polymer - poly-γ-glutamic acid (γ-PGA) matrix. Although antifreeze activity γ-PGA well known, it has not been used for maintaining during drying. aim this study was test effect (produced by B. subtilis natto ATCC 15245) on and toxigenic...
A number of genetic diseases, including cystic fibrosis, have been identified as disorders protein trafficking associated with retention mutant within the endoplasmic reticulum. In presence benzo(c)quinolizinium drugs, MPB-07 and its congener MPB-91, we show activation fibrosis transmembrane conductance regulator (CFTR) delF508 channels in IB3-1 human cells, which express endogenous levels delF508-CFTR. These drugs were without effect on Ca2+-activated Cl– transport, whereas...
Renal cell carcinoma (RCC) is histopathologically heterogeneous with clear and papillary the most common subtypes. The frequent molecular abnormality in RCC VHL inactivation but promoter methylation of tumour suppressor genes both subtypes RCC. To investigate whether CpG status was influenced by histopathology we performed high-throughput epigenetic profiling using Illumina Goldengate Methylation Array 62 (29 from von Hippel-Lindau (VHL) disease patients, 20 sporadic wild type 13 RCC).43...
AbstractAn initiating role for RAS oncogene mutation in several epithelial cancers is supported by its high incidence early-stage tumors and ability to induce proliferation the corresponding normal cells vitro. Using retroviral transduction of thyroid as a model we ask here: (i) how mutant can long-term an cell contrast premature senescence observed fibroblasts; (ii) what “clock” which eventually triggers spontaneous growth arrest even clones generated RAS. The early response activation...
Abstract Purpose: Familial renal cell carcinoma (RCC) is genetically heterogeneous. The most common histopathologic subtype of sporadic and familial RCC clear (cRCC) von Hippel-Lindau (VHL) disease the cause inherited cRCC. cRCC may also be associated with chromosome 3 translocations has recently been described in patients Birt-Hogg-Dube (BHD) syndrome, caused by germline FLCN mutation. Fewer than 20 kindreds without VHL or a constitutional translocation have described. purpose this...
Promoter region hypermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many human cancers. Previously, to identify candidate epigenetically inactivated TSGs renal cell carcinoma (RCC), we monitored changes expression four RCC lines after treatment with the demethylating agent 5-azacytidine. This enabled us HAI-2/SPINT2 as novel TSG. To further TSGs, undertook bioinformatic molecular genetic evaluation 60 genes differentially...
Aberrant DNA methylation, in particular promoter hypermethylation and transcriptional silencing of tumor suppressor genes, has an important role the development many human cancers, including renal cell carcinoma (RCC). Indeed, apart from mutations well studied von Hippel-Lindau gene (VHL), mutation frequency rates known genes RCC are generally low, but number found to show frequent inactivation by methylation continues grow. Here, we review identified as epigenetically silenced their...