A5090331548- PARP inhibition in cancer therapy
- BRCA gene mutations in cancer
- Ovarian cancer diagnosis and treatment
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Molecular Biology Techniques and Applications
- Lung Cancer Research Studies
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Genetic factors in colorectal cancer
- Cancer Diagnosis and Treatment
- Virus-based gene therapy research
- Lung Cancer Treatments and Mutations
- Immune Cell Function and Interaction
- Bone health and treatments
- T-cell and B-cell Immunology
- T-cell and Retrovirus Studies
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Fibroblast Growth Factor Research
- Radio Frequency Integrated Circuit Design
- Acute Myeloid Leukemia Research
- Hematopoietic Stem Cell Transplantation
- Gene expression and cancer classification
- Lymphoma Diagnosis and Treatment
University of Manchester
1999-2024
Cancer Research UK
2024
Cancer Research UK Manchester Institute
2012-2023
Guy's and St Thomas' NHS Foundation Trust
2013
St Thomas' Hospital
2013
Epistem (United Kingdom)
2002-2008
AstraZeneca (United Kingdom)
2007
Ontario Institute for Cancer Research
1988-1997
Cancer Institute (WIA)
1996-1997
Montreal Clinical Research Institute
1996
Small cell lung cancer (SCLC) is characterized by morphologic, epigenetic and transcriptomic heterogeneity. Subtypes based upon predominant transcription factor expression have been defined that, in mouse models lines, exhibit potential differential therapeutic vulnerabilities, with epigenetically distinct SCLC subtypes also described. The clinical relevance of these unclear, due part to challenges obtaining tumor biopsies for reliable profiling. Here we describe a robust workflow...
BackgroundOver the past decade, numerous reports describe generation and increasing utility of non-small-cell lung cancer (NSCLC) patient-derived xenografts (PDX) from tissue biopsies. While PDX have proven useful for genetic profiling preclinical drug testing, requirement a biopsy limits available patient population, particularly those with advanced oligometastatic disease. Conversely, 'liquid biopsies' such as circulating tumour cells (CTCs) are minimally invasive easier to obtain. Here,...
Abstract Cancers of Unknown Primary (CUP) remains a diagnostic and therapeutic challenge due to biological heterogeneity poor responses standard chemotherapy. Predicting tissue-of-origin (TOO) molecularly could help refine this diagnosis, with tissue acquisition barriers mitigated via liquid biopsies. However, TOO biopsies are unexplored in CUP cohorts. Here we describe CUPiD, machine learning classifier for accurate predictions across 29 tumour classes using circulating cell-free DNA...
In the absence of major dysmotility, esophageal manometry with water swallows rarely explains causes symptoms and disease. This methodology development study assessed function during a test meal in patients reflux asymptomatic controls. The impact this approach on manometric diagnosis clinical outcome was reviewed.18 10 healthy volunteers underwent high resolution (HRM) 5 mL swallows, 200 drink, standardized solid followed by min postprandial observation. number associated dysfunction (SAD)...
SCLC accounts for approximately 250,000 deaths worldwide each year. Acquisition of adequate tumor biopsy samples is challenging, and liquid biopsies present an alternative option patient stratification response monitoring.
Thyroid hormone (T3) and the T3 receptor (TR) alpha gene are essential for bone development whereas adult hyperthyroidism increases risk of osteoporotic fracture. We isolated fibroblast growth factor receptor-1 (FGFR1) as a T3-target in osteoblasts by subtraction hybridization. FGFR1 mRNA was induced 2- to 3-fold treated with 6-48 h, protein stimulated 4-fold. Induction independent half-life abolished actinomycin D cycloheximide, indicating involvement an intermediary protein. Fibroblast 2...
BackgroundThe application of precision medicine in oncology requires in-depth characterisation a patient's tumours and the dynamics their responses to treatment.Patients methodsWe used next-generation sequencing circulating cell-free DNA (cfDNA) monitor response KIT p.L576P-mutant metastatic vaginal mucosal melanoma sequential targeted, immuno- chemotherapy.ResultsDespite mutation, imatinib was mixed. Unfortunately, were not accessible for molecular analysis. To study mechanism underlying...
The characteristics of endothelium‐dependent hyperpolarization in rat hepatic artery have been further investigated the presence inhibitors cyclo‐oxygenase and nitric oxide synthase. Using sharp micro‐electrodes, smooth muscle induced by acetylcholine, KCl or 1‐ethyl‐2‐benzimidazolinone (1‐EBIO) intact arteries was abolished 30 μ M barium plus 500 n ouabain. In vessels without endothelium, not reduced alone. However, effects were partially inhibited 100 ouabain essentially both endothelium...
We have developed a sensitive quantitative RT–PCR procedure suitable for the analysis of small samples, including single cells, and used it to measure levels potassium channel mRNAs in panel human tissues numbers cells grown culture. The method involves an initial global amplification cDNA derived from all added polyadenylated mRNA followed by individual genes using specific primers. In order facilitate rapid accurate processing we adapted approach allow use of<mml:math...
Overproduction of parathyroid hormone-related protein (PTHRP) occurs in a high proportion primary breast cancers (PBC) and is strongly implicated their metastatic spread to bone. Although the PTHRP-receptor (PTHRP-R) often coexpressed with PTHRP PBC, its role regulating cancer cell proliferation metastases bone remains unclear. The aims this study were determine expression PTHRP-R (BM) investigate effects overexpression on proliferation. occurred 85% (11 out 13) BM compared 58% (39 67) PBC....
Nine high copy number mutations of plasmid R6-5, representing five phenotypically distinct groups, have been identified by DNA sequencing. In each mutant examined, a single nucleotide change was found. The effects the on possible gene products, and DNA-RNA secondary structure, were analyzed compared with observed phenotypes. results this study exclude possibility that primary replication control element, product copA gene, is polypeptide, they are consistent model which has following...