Immunofluorescence microscopy-based detection of ssDNA foci by BrdU in mammalian cells

Acknowledgments This work was funded by the MRC Program grant MC_PC 12001/1 and MC_UU_00001/1 to K.R., and S.K. was supported by the MRC Oxford Institute of Radiation Oncology (OIRO) Cancer Research UK (CRUK) Studentship. We thank Dr. Rhodri Wilson from the microscopy imaging core (University of Oxford, Department of Oncology) for his technical advice and assistance. Graphical abstract was created with BioRender.Peer reviewedPublisher PD

Association of Bacteroides acidifaciens relative abundance with high-fibre diet-associated radiosensitisation

Funding Information: This work was funded by Cancer Research UK Programme grant C5255/ A23755 and Wellcome Trust Investigator Award 209397/Z/17/Z. The funding body had no role in the design of the study; in the collection, analysis, and interpretation of data; or in the writing of the manuscript. Acknowledgements We thank Professor Simon Kroll and Dr. Anderson Ryan for their very helpful comments. We thank Dr. Jia-Yu Ke at Research Diets, Inc. for formulation of the mouse diets, Dr. Lisa Folkes for assistance with the faecal butyrate quantification, and Omega Bioservices (Georgia, USA) for the 16S rRNA gene sequencing on a MiSeq platform.Peer reviewedPublisher PD

The role of dietary supplements, including biotics, glutamine, polyunsaturated fatty acids and polyphenols, in reducing gastrointestinal side effects in patients undergoing pelvic radiotherapy : A systematic review and meta-analysis

Funding Information: This work was supported by Cancer Research UK Programme grant [C5255/A23755]. Chee Kin Then’s DPhil is funded by the Clarendon Fund, Balliol College and CRUK. The funding body had no role in the study design, collection, analysis, interpretation of data or in writing the manuscript.Peer reviewedPublisher PD

Field-cycling imaging in ovarian cancer : a novel technology

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DNA repair gene XRCC1 polymorphisms and bladder cancer risk

BACKGROUND: Cigarette smoking and chemical occupational exposure are the main known risk factors for bladder transitional cell carcinoma (TCC). Oxidative DNA damage induced by carcinogens present in these exposures requires accurate base excision repair (BER). The XRCC1 protein plays a crucial role in BER by acting as a scaffold for other BER enzymes. Variants in the XRCC1 gene might alter protein structure or function or create alternatively spliced proteins which may influence BER efficiency and hence affect individual susceptibility to bladder cancer. Recent epidemiological studies have shown inconsistent associations between these polymorphisms and bladder cancer. To clarify the situation, we conducted a comprehensive analysis of 14 XRCC1 polymorphisms in a case-control study involving more than 1100 subjects. RESULTS: We found no evidence of an association between any of the 14 XRCC1 polymorphisms and bladder cancer risk. However, we found carriage of the variant Arg280His allele to be marginally associated with increased bladder cancer risk compared to the wild-type genotype (adjusted odds ratio [95% confidence interval], 1.50 [0.98–2.28], p = 0.06). The association was stronger for current smokers such that individuals carrying the variant 280His allele had a two to three-fold increased risk of bladder cancer compared to those carrying the wildtype genotype (p = 0.09). However, the evidence for gene-environment interaction was not statistically significant (p = 0.45). CONCLUSION: We provide no evidence of an association between polymorphisms in XRCC1 and bladder cancer risk, although our study had only limited power to detect the association for low frequency variants, such as Arg280His

Greater utility of molecular subtype rather than epithelial-to-mesenchymal transition (EMT) markers for prognosis in high-risk non-muscle-invasive (HGT1) bladder cancer

Funding Information: ECO and AEK were funded by CRUK programme grant C5255/A23755. We would like to thank Marcus Green for cutting the sections and giving advice on optimisation of antibodies and to Dr Jong‐Wei Hsu for advice on antibody selection. LB was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health. LB is part of the PathLAKE digital pathology consortium. These new Centres are supported by a £50m investment from the Data to Early Diagnosis and Precision Medicine strand of the UK government's Industrial Strategy Challenge Fund, managed and delivered by UK Research and Innovation (UKRI).Peer reviewedPublisher PD

The Histone Deacetylase Inhibitor Romidepsin Spares Normal Tissues While Acting as an Effective Radiosensitizer in Bladder Tumors in Vivo

Funding Information: This work was funded by Cancer Research UK (CRUK; C5255/A23755). J.L.R. was funded by CRUK (project grant C15140/A19817). C.K.T. was funded by a CRUK DPhil Research Training and Support Grant, the Balliol College Alfred Douglas Stone Scholarship, and the University of Oxford Clarendon Fund. S.K. was funded by a CRUK/MRC Oxford Institute of Radiation Oncology CRUK studentship.Peer reviewedPublisher PD

Exploiting dietary fibre and the gut microbiota in pelvic radiotherapy patients

ACKNOWLEDGEMENTS We thank Mrs Pat Bain for her assistance in creating Fig. 1. Funding Information: AEK’s salary is funded by Friends of ANCHOR and the University of Aberdeen Development Trust. CKT’s DPhil was funded by the Clarendon Fund, Balliol College, Oxford and Cancer Research UK. JK’s summer research project was funded by a Royal College of Radiologists’ Summer Undergraduate Research Fellowship. The authors received no specific funding for this work.Peer reviewedPublisher PD

SPRTN protease-cleaved MRE11 decreases DNA repair and radiosensitises cancer cells

Funding Information: This work was funded by CRUK Programme Grant C5255/A23755. Acknowledgements Mass spectrometry analysis was performed in the MS laboratory at the Target discovery institute—NDM (Oxford) led by Benedikt M. Kessler. We thank Drs. Eva McGrowder and Blaz Groselj for processing of primary bladder tumour samples to produce cell-free extracts. Data availability The LC-MS/MS proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE48 partner repository with the dataset identifier PXD017964 and 10.6019/PXD017964.Peer reviewedPublisher PD

The role of microRNA-binding site polymorphisms in DNA repair genes as risk factors for bladder cancer and breast cancer and their impact on radiotherapy outcomes

MicroRNAs (miRNAs) are involved in post-transcriptional regulation of gene expression through binding to messenger RNAs (mRNA) thereby promoting mRNA degradation or altered translation. A single-nucleotide polymorphism (SNP) located within a miRNA-binding site could thus alter mRNA translation and influence cancer risk and treatment response. The common SNPs located within the 3′-untranslated regions of 20 DNA repair genes were analysed for putative miRNA-binding sites using bioinformatics algorithms, calculating the difference in Gibbs free binding energy (ΔΔG) for each wild-type versus variant allele. Seven SNPs were selected to be genotyped in germ line DNAs both from a bladder cancer case–control series (752 cases and 704 controls) and 202 muscle-invasive bladder cancer radiotherapy cases. The PARP-1 SNP rs8679 was also genotyped in a breast cancer case–control series (257 cases and 512 controls). Without adjustment for multiple testing, multivariate analysis demonstrated an association with increased bladder cancer risk with PARP1 rs8679 (Ptrend = 0.05) while variant homozygotes of PARP1 rs8679 were also noted to have an increased breast cancer risk (P = 0.03). In the radiotherapy cases, carriers of the RAD51 rs7180135 minor allele had improved cancer-specific survival (hazard ratio 0.52, 95% confidence interval 0.31–0.87, P = 0.01). This is the first report of associations between DNA repair gene miRNA-binding site SNPs with bladder and breast cancer risk and radiotherapy outcomes. If validated, these findings may give further insight into the biology of bladder carcinogenesis, allow testing of the RAD51 SNP as a potential predictive biomarker and also reveal potential targets for new cancer treatments