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

Inhibition of double-strand break non-homologous end-joining by cisplatin adducts in human cell extracts

The effect of cis-diaminedichloroplatinum(II) (cisplatin) DNA damage on the repair of double-strand breaks by non-homologous end-joining (NHEJ) was determined using cell-free extracts. NHEJ was dramatically decreased when plasmid DNA was damaged to contain multiple types of DNA adducts, along the molecule and at the termini, by incubation of DNA with cisplatin; this was a cisplatin concentration-dependent effect. We investigated the effect a single GTG cisplatination site starting 10 bp from the DNA termini would have when surrounded by the regions of AT-rich DNA which were devoid of the major adduct target sequences. Cisplatination of a substrate containing short terminal 13–15 bp AT-rich sequences reduced NHEJ to a greater extent than that of a substrate with longer (31–33 bp) AT-rich sequences. However, cisplatination at the single GTG site within the AT sequence had no significant effect on NHEJ, owing to the influence of additional minor monoadduct and dinucleotide adduct sites within the AT-rich region and owing to the influence of cisplatination at sites upstream of the AT-rich regions. We then studied the effect on NHEJ of one cis-[Pt(NH(3))(2){d(GpTpG)-N7(1),-N7(3)} [abbreviated as 1,3-d(GpTpG)] cisplatin adduct in the entire DNA molecule, which is more reflective of the situation in vivo during concurrent chemoradiation. The presence of a single 1,3-d(GpTpG) cisplatin adduct 10 bases from each of the two DNA ends to be joined resulted in a small (30%) but significant decrease in NHEJ efficiency. This process, which was DNA-dependent protein kinase and Ku dependent, may in part explain the radiosensitizing effect of cisplatin administered during concurrent chemoradiation

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

How do tumours outside the gastrointestinal tract respond to dietary fibre supplementation?

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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