A5065038118- Prostate Cancer Treatment and Research
- Advanced Proteomics Techniques and Applications
- Medical Imaging Techniques and Applications
- Radiomics and Machine Learning in Medical Imaging
- Cancer, Hypoxia, and Metabolism
- Advanced MRI Techniques and Applications
- HER2/EGFR in Cancer Research
- DNA Repair Mechanisms
- Metabolomics and Mass Spectrometry Studies
- RNA modifications and cancer
- Molecular Biology Techniques and Applications
- Advanced Radiotherapy Techniques
- Lung Cancer Treatments and Mutations
- PARP inhibition in cancer therapy
- Lung Cancer Diagnosis and Treatment
- Cancer, Lipids, and Metabolism
- Cancer Genomics and Diagnostics
- Melanoma and MAPK Pathways
- Macrophage Migration Inhibitory Factor
- Protein Tyrosine Phosphatases
- Computational Drug Discovery Methods
- 14-3-3 protein interactions
- Click Chemistry and Applications
- Advances in Oncology and Radiotherapy
- Glioma Diagnosis and Treatment
University of Oxford
2016-2025
CRUK/MRC Oxford Institute for Radiation Oncology
2013-2024
Oxford University Hospitals NHS Trust
1966-2024
National Health Service
2021-2023
Medical Research Council
2016-2022
University of Cambridge
1990-2022
University of Manchester
2022
Newcastle University
2022
University of Glasgow
2022
Imperial College London
2022
To identify approaches to target DNA repair vulnerabilities in cancer, we discovered nanomolar potent, selective, low molecular weight (MW), allosteric inhibitors of the polymerase function Polθ, including ART558. ART558 inhibits major Polθ-mediated process, Theta-Mediated End Joining, without targeting Non-Homologous Joining. In addition, elicits damage and synthetic lethality BRCA1- or BRCA2-mutant tumour cells enhances effects a PARP inhibitor. Genetic perturbation screening revealed that...
Abstract Tumour hypoxia renders cancer cells resistant to therapy, resulting in markedly worse clinical outcomes. To find candidate compounds that reduce tumours, we conduct a high-throughput screen for oxygen consumption rate (OCR) reduction and identify number of drugs with this property. For study focus on the anti-malarial, atovaquone. Atovaquone rapidly decreases OCR by more than 80% wide range cell lines at pharmacological concentrations. In addition, atovaquone eradicates FaDu, HCT116...
POLQ is a key effector of DSB repair by microhomology-mediated end-joining (MMEJ) and overexpressed in many cancers. inhibitors confer synthetic lethality HR Shieldin-deficient cancer cells, which has been proposed to reflect critical dependence on the pathway MMEJ. Whether also operates independent MMEJ remains unexplored. Here, we show that POLQ-deficient cells accumulate post-replicative ssDNA gaps upon BRCA1/2 loss or PARP inhibitor treatment. Biochemically, cooperation between helicase...
Offering an approach that focuses on the origins of mental health rather than beginnings illness, this book outlines how men and women can recognize resilient traits they possess foster strength to overcome tragedy. An inspiring invigorating book! I recommAnd it courageous who struggle each day their own cruel pasts, therapists work with them, anyone interested in relationship between adult development health.''--Robert Kegan, Harvard University Massachusetts School Professional Psychology
Abstract The effectiveness of radiotherapy treatment could be significantly improved if tumor cells rendered more sensitive to ionizing radiation (IR) without altering the sensitivity normal tissues. However, many key therapeutically exploitable mechanisms that determine intrinsic radiosensitivity are largely unknown. We have conducted a small interfering RNA (siRNA) screen 200 genes involved in DNA damage repair aimed at identifying whose knockdown increased radiosensitivity. Parallel siRNA...
Clinical, haematological, biochemical, bacteriological, histological, and immunological data in 300 patients with ulcerative colitis have been examined special reference to liver disease dysfunction. Biochemical dysfunction of the is common. Forty-five (15 per cent) had an abnormality one or more three basic tests used this study: bromsulphthalein retention test, serum glutamate pyruvate transaminase, alkaline phosphatase. Further biochemical contributed little additional information. A...
DNA double-strand breaks (DSBs) are toxic lesions, which if improperly repaired can result in cell death or genomic instability. DSB repair is usually facilitated by the classical non-homologous end joining (C-NHEJ), homologous recombination (HR) pathways. However, a mutagenic alternative NHEJ pathway, microhomology-mediated (MMEJ), also be deployed. While MMEJ suppressed C-NHEJ, relationship between HR and less clear. Here, we describe role for genes suppressing human cells. By monitoring...
Abstract Purpose: Tumor hypoxia fuels an aggressive tumor phenotype and confers resistance to anticancer treatments. We conducted a clinical trial determine whether the antimalarial drug atovaquone, known mitochondrial inhibitor, reduces in non–small cell lung cancer (NSCLC). Patients Methods: with NSCLC scheduled for surgery were recruited sequentially into two cohorts: cohort 1 received oral atovaquone at standard dose of 750 mg twice daily, while 2 did not. Primary imaging endpoint was...
In light of the disappointing termination clinical trials with potent complex I inhibitors, such as IACS-010759, justification for oxidative phosphorylation inhibitors and mitochondrial targeting strategies has been called into question. Consideration these agents' potency, tissue selectivity toxicity demonstrate what lessons can be learned from this failure where new opportunities lie.
There are few data on pesticide exposures of migrant Latino farmworker children, and access to this vulnerable population is often difficult. In paper we describe a community-based approach implement culturally appropriate research methods with community in Oregon. Assessments were conducted 96 homes 24 grower two agricultural communities Measurements included surveys use work protection practices analyses home-dust samples for residues major organophosphates used area crops. Results...
Journal Article A broad spectrum of human papillomavirus types is present in the skin Australian patients with non‐melanoma cancers and solar keratosis Get access O. Forslund, Forslund Department Medical Microbiology, Malmö University Hospital, Lund University, SE‐205 02 Malmö, SwedenInfectious Diseases Laboratories, Institute Veterinary Science, Adelaide, Australia Ola Forslund. E‐mail: ola.forslund@mikrobiol.mas.lu.se Search for other works by this author on: Oxford Academic Google Scholar...
Depletion of POLQ (DNA polymerase theta) has recently been shown to render tumour cells more sensitive radiotherapy whilst having little or no effect on normal tissues.This finding led us investigate whether tumours that overexpress are associated with an adverse outcome.We therefore correlated the clinical outcomes two retrospective series patients early breast cancer expression levels POLQ, as determined by microarray gene analysis.We found a significant number overexpressed and...
SUMMARY Phenobarbitone was administered to four adult volunteers in doses similar those used for control of grand mal seizures epileptics. Blood‐levels phenobarbitone were determined at selected points during and again after the study, which lasted a month. Perceptual motor performance measured on 6 tasks before study began within 24 hours each blood sample being taken. Four factors found be important determining level performance: (1) blood‐level drug; (2) difficulty (3) duration task; (4)...
Clinical, haematological, biochemical, bacteriological, histological, and immuno-logical data of 100 patients with Crohn's disease have been examined special reference to liver dysfunction. Several significant points emerged from the clinical data. There was a high frequency colonic involvement (57 per cent), also very proportion (48 cent) systemic complications, commonest complications being iritis (19 sacro-ileitis (15 cent). Nearly three-quarters (71 had operated on at some time 57 cent...
Innovation and progress in radiation oncology depend on discovery insights realized through research biology. Radiobiology has led to fundamental scientific insights, from the of stem/progenitor cells definition signal transduction pathways activated by ionizing that are now recognized as integral DNA damage response (DDR). Radiobiological discoveries guiding clinical trials test therapy combined with inhibitors DDR kinases DNA-dependent protein kinase (DNA-PK), ataxia telangiectasia mutated...
Targeting cancers dependent on DNA polymerase θ has considerable clinical potential
Abstract Background The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated in tumor cells and promotes cell survival after radiation-induced DNA damage. Because the may not be completely inhibited blockade of PI3K itself, due to feedback through mammalian target rapamycin (mTOR), more effective inhibition might expected by targeting both mTOR inhibition. Materials methods We investigated effect two dual PI3K/mTOR (both mTORC1 mTORC2) inhibitors, NVP-BEZ235 NVP-BGT226, on SQ20B...