Institution
University Hospitals of Leicester NHS Trust
Healthcare•Leicester, United Kingdom•
About: University Hospitals of Leicester NHS Trust is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Medicine. The organization has 2799 authors who have published 3018 publications receiving 76587 citations. The organization is also known as: University Hospitals of Leicester.
Topics: Population, Medicine, Randomized controlled trial, Health care, Cancer
Papers published on a yearly basis
Papers
More filters
••
TL;DR: This review critically addresses the extent to which the in vitro significance of oxidative DNA damage has relevance for the pathogenesis of disease, drawing attention to the multiplicity of proteins with repair activities along with a number of poorly considered effects of damage.
Abstract: Oxidative DNA damage is an inevitable consequence of cellular metabolism, with a propensity for increased levels following toxic insult. Although more than 20 base lesions have been identified, only a fraction of these have received appreciable study, most notably 8-oxo-2'deoxyguanosine. This lesion has been the focus of intense research interest and been ascribed much importance, largely to the detriment of other lesions. The present work reviews the basis for the biological significance of oxidative DNA damage, drawing attention to the multiplicity of proteins with repair activities along with a number of poorly considered effects of damage. Given the plethora of (often contradictory) reports describing pathological conditions in which levels of oxidative DNA damage have been measured, this review critically addresses the extent to which the in vitro significance of such damage has relevance for the pathogenesis of disease. It is suggested that some shortcomings associated with biomarkers, along with gaps in our knowledge, may be responsible for the failure to produce consistent and definitive results when applied to understanding the role of DNA damage in disease, highlighting the need for further studies.
2,910 citations
••
University of Oxford1, University of Bristol2, Cardiff University3, North Bristol NHS Trust4, Royal Victoria Infirmary5, University of Edinburgh6, University of Sheffield7, University Hospitals of Leicester NHS Trust8, Leeds Teaching Hospitals NHS Trust9, Freeman Hospital10, University of Cambridge11
TL;DR: At a median of 10 years, prostate-cancer-specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments.
Abstract: BACKGROUND The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. METHODS We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. RESULTS There were 17 prostate-cancer–specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P=0.004 for the overall comparison). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P<0.001 for the overall comparison). CONCLUSIONS At a median of 10 years, prostate-cancer–specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring.
2,016 citations
••
TL;DR: Mepolizumab is an effective and well tolerated treatment that reduces the risk of asthma exacerbations in patients with severe eosinophilic asthma.
1,765 citations
••
TL;DR: The weight of evidence strongly suggests a link between such damage and the pathogenesis of disease, and the role of 8-OH-dG in disease, although exact roles remain to be elucidated.
Abstract: The generation of reactive oxygen species may be both beneficial to cells, performing a function in inter- and intracellular signalling, and detrimental, modifying cellular biomolecules, accumulation of which has been associated with numerous diseases. Of the molecules subject to oxidative modification, DNA has received the greatest attention, with biomarkers of exposure and effect closest to validation. Despite nearly a quarter of a century of study, and a large number of base- and sugar-derived DNA lesions having been identified, the majority of studies have focussed upon the guanine modification, 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-OH-dG). For the most part, the biological significance of other lesions has not, as yet, been investigated. In contrast, the description and characterisation of enzyme systems responsible for repairing oxidative DNA base damage is growing rapidly, being the subject of intense study. However, there remain notable gaps in our knowledge of which repair proteins remove which lesions, plus, as more lesions identified, new processes/substrates need to be determined. There are many reports describing elevated levels of oxidatively modified DNA lesions, in various biological matrices, in a plethora of diseases; however, for the majority of these the association could merely be coincidental, and more detailed studies are required. Nevertheless, even based simply upon reports of studies investigating the potential role of 8-OH-dG in disease, the weight of evidence strongly suggests a link between such damage and the pathogenesis of disease. However, exact roles remain to be elucidated.
1,268 citations
••
University Health Network1, University Hospitals of Leicester NHS Trust2, Imperial College London3, Nanjing University4, Mayo Clinic5, Austral University of Chile6, RWTH Aachen University7, University of North Carolina at Chapel Hill8, University of Michigan9, Complutense University of Madrid10, University of California, Los Angeles11, Columbia University12, University of Sydney13, Ohio State University14, Post Graduate Institute of Medical Education and Research15, Université de Montréal16, The Chinese University of Hong Kong17, Radboud University Nijmegen18
1,132 citations
Authors
Showing all 2820 results
Name | H-index | Papers | Citations |
---|---|---|---|
Nilesh J. Samani | 149 | 779 | 113545 |
Kamyar Kalantar-Zadeh | 118 | 1025 | 56187 |
Ian D. Pavord | 108 | 575 | 47691 |
Richard C. Trembath | 107 | 368 | 41128 |
Christopher E. Brightling | 103 | 552 | 44358 |
Stuart J. H. Biddle | 102 | 484 | 41251 |
Andrew J. Wardlaw | 92 | 311 | 33721 |
Kamlesh Khunti | 91 | 1030 | 37429 |
Melanie J. Davies | 89 | 814 | 36939 |
Kenneth J. O'Byrne | 87 | 629 | 39193 |
Martin J. S. Dyer | 85 | 373 | 24909 |
Bryan Williams | 82 | 454 | 40798 |
Stephen Lory | 79 | 176 | 24333 |
Alex J. Mitchell | 79 | 251 | 24227 |
Martin D. Tobin | 72 | 218 | 34028 |