Institution
Sunnybrook Health Sciences Centre
Healthcare•Toronto, Ontario, Canada•
About: Sunnybrook Health Sciences Centre is a healthcare organization based out in Toronto, Ontario, Canada. It is known for research contribution in the topics: Population & Medicine. The organization has 7689 authors who have published 15236 publications receiving 523019 citations. The organization is also known as: Sunnybrook.
Topics: Population, Medicine, Health care, Breast cancer, Cancer
Papers published on a yearly basis
Papers
More filters
••
TL;DR: Results showed that miR-93 promotes tumor growth and angiogenesis by suppressing, at least in part, integrin-β8 expression, which is associated with cell death in tumor mass and in human glioblastoma.
Abstract: It has been reported that the miR-106b∼25 cluster, a paralog of the miR-17∼92 cluster, possesses oncogenic activities However, the precise role of each microRNA (miRNA) in the miR-106b∼25 cluster is not yet known In this study, we examined the function of miR-93, one of the microRNAs within the miR-106b∼25 cluster, in angiogenesis and tumor formation We found that miR-93 enhanced cell survival, promoted sphere formation and augmented tumor growth Most strikingly, when miR-93-overexpressing U87 cells were co-cultured with endothelial cells, they supported endothelial cell spreading, growth, migration and tube formation In vivo studies revealed that miR-93-expressing cells induced blood vessel formation, allowing blood vessels to extend to tumor tissues in high densities Angiogenesis promoted by miR-93 in return facilitated cell survival, resulting in enhanced tumor growth We further showed that integrin-β8 is a target of miR-93 Higher levels of integrin-β8 are associated with cell death in tumor mass and in human glioblastoma Silencing of integrin-β8 expression using small interfering RNA promoted cell proliferation, whereas ectopic expression of integrin-β8 decreased cell growth These findings showed that miR-93 promotes tumor growth and angiogenesis by suppressing, at least in part, integrin-β8 expression Our results suggest that inhibition of miR-93 function may be a feasible approach to suppress angiogenesis and tumor growth
309 citations
••
Newcastle University1, Mayo Clinic2, University of Strasbourg3, Nagoya University4, University of Cambridge5, McGill University6, King's College London7, University of Exeter8, University of Chieti-Pescara9, University of Miami10, University of California, San Diego11, Northwestern University12, Harvard University13, Columbia University14, Osaka University15, Cleveland Clinic16, University of Sydney17, Sunnybrook Health Sciences Centre18, University of Washington19, University College London20, University of Toronto21
TL;DR: This work proposes operationalized diagnostic criteria for probable and possible mild cognitive impairment with Lewy bodies, which are intended for use in research settings pending validation for Use in clinical practice and are compatible with current criteria for other prodromal neurodegenerative disorders including Alzheimer and Parkinson disease.
Abstract: The prodromal phase of dementia with Lewy bodies (DLB) includes (1) mild cognitive impairment (MCI), (2) delirium-onset, and (3) psychiatric-onset presentations. The purpose of our review is to determine whether there is sufficient information yet available to justify development of diagnostic criteria for each of these. Our goal is to achieve evidence-based recommendations for the recognition of DLB at a predementia, symptomatic stage. We propose operationalized diagnostic criteria for probable and possible mild cognitive impairment with Lewy bodies, which are intended for use in research settings pending validation for use in clinical practice. They are compatible with current criteria for other prodromal neurodegenerative disorders including Alzheimer and Parkinson disease. Although there is still insufficient evidence to propose formal criteria for delirium-onset and psychiatric-onset presentations of DLB, we feel that it is important to characterize them, raising the index of diagnostic suspicion and prioritizing them for further investigation.
308 citations
••
Institute of Cancer Research1, The Royal Marsden NHS Foundation Trust2, Northwood University3, James Cook University Hospital4, Sunnybrook Health Sciences Centre5, Clatterbridge Cancer Centre NHS Foundation Trust6, Queen's University Belfast7, Cambridge University Hospitals NHS Foundation Trust8, Cardiff University9, Churchill Hospital10, University of Leicester11, Freeman Hospital12, Coventry Health Care13, McMaster University14, Beatson West of Scotland Cancer Centre15
TL;DR: The results suggest that substantially shortening treatment courses with stereotactic body radiotherapy does not increase either gastrointestinal or genitourinary acute toxicity.
Abstract: Summary Background Localised prostate cancer is commonly treated with external-beam radiotherapy. Moderate hypofractionation has been shown to be non-inferior to conventional fractionation. Ultra-hypofractionated stereotactic body radiotherapy would allow shorter treatment courses but could increase acute toxicity compared with conventionally fractionated or moderately hypofractionated radiotherapy. We report the acute toxicity findings from a randomised trial of standard-of-care conventionally fractionated or moderately hypofractionated radiotherapy versus five-fraction stereotactic body radiotherapy for low-risk to intermediate-risk localised prostate cancer. Methods PACE is an international, phase 3, open-label, randomised, non-inferiority trial. In PACE-B, eligible men aged 18 years and older, with WHO performance status 0–2, low-risk or intermediate-risk prostate adenocarcinoma (Gleason 4 + 3 excluded), and scheduled to receive radiotherapy were recruited from 37 centres in three countries (UK, Ireland, and Canada). Participants were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group, to conventionally fractionated or moderately hypofractionated radiotherapy (78 Gy in 39 fractions over 7·8 weeks or 62 Gy in 20 fractions over 4 weeks, respectively) or stereotactic body radiotherapy (36·25 Gy in five fractions over 1–2 weeks). Neither participants nor investigators were masked to allocation. Androgen deprivation was not permitted. The primary endpoint of PACE-B is freedom from biochemical or clinical failure. The coprimary outcomes for this acute toxicity substudy were worst grade 2 or more severe Radiation Therapy Oncology Group (RTOG) gastrointestinal or genitourinary toxic effects score up to 12 weeks after radiotherapy. Analysis was per protocol. This study is registered with ClinicalTrials.gov , NCT01584258 . PACE-B recruitment is complete and follow-up is ongoing. Findings Between Aug 7, 2012, and Jan 4, 2018, we randomly assigned 874 men to conventionally fractionated or moderately hypofractionated radiotherapy (n=441) or stereotactic body radiotherapy (n=433). 432 (98%) of 441 patients allocated to conventionally fractionated or moderately hypofractionated radiotherapy and 415 (96%) of 433 patients allocated to stereotactic body radiotherapy received at least one fraction of allocated treatment. Worst acute RTOG gastrointestinal toxic effect proportions were as follows: grade 2 or more severe toxic events in 53 (12%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 43 (10%) of 415 patients in the stereotactic body radiotherapy group (difference −1·9 percentage points, 95% CI −6·2 to 2·4; p=0·38). Worst acute RTOG genitourinary toxicity proportions were as follows: grade 2 or worse toxicity in 118 (27%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 96 (23%) of 415 patients in the stereotactic body radiotherapy group (difference −4·2 percentage points, 95% CI −10·0 to 1·7; p=0·16). No treatment-related deaths occurred. Interpretation Previous evidence (from the HYPO-RT-PC trial) suggested higher patient-reported toxicity with ultrahypofractionation. By contrast, our results suggest that substantially shortening treatment courses with stereotactic body radiotherapy does not increase either gastrointestinal or genitourinary acute toxicity. Funding Accuray and National Institute of Health Research.
308 citations
••
The George Institute for Global Health1, Peking University2, Sunnybrook Health Sciences Centre3, University of Oxford4, University of British Columbia5, University Health Network6, University of California, Los Angeles7, University College London8, Johns Hopkins University9, University of Hong Kong10, University of Queensland11, Charles Darwin University12, University of Leicester13, RWTH Aachen University14, Mario Negri Institute for Pharmacological Research15, Indiana University16
TL;DR: The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) study as discussed by the authors was a multicenter, double-blind, randomized clinical trial designed to recruit 750 participants with IgA nephropathy (proteinuria greater than 1 g/d and estimated glomerular filtration rate [eGFR] of 20 to 120 mL/min/1).
Abstract: Importance Guidelines recommend corticosteroids in patients with IgA nephropathy and persistent proteinuria, but the effects remain uncertain. Objective To evaluate the efficacy and safety of corticosteroids in patients with IgA nephropathy at risk of progression. Design, Setting, and Participants The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) study was a multicenter, double-blind, randomized clinical trial designed to recruit 750 participants with IgA nephropathy (proteinuria greater than 1 g/d and estimated glomerular filtration rate [eGFR] of 20 to 120 mL/min/1.73 m 2 after at least 3 months of blood pressure control with renin-angiotensin system blockade] and to provide follow-up until 335 primary outcomes occurred. Interventions Patients were randomized 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/d; maximum, 48 mg/d) (n = 136) or matching placebo (n = 126) for 2 months, with subsequent weaning over 4 to 6 months. Main Outcomes and Measures The primary composite outcome was end-stage kidney disease, death due to kidney failure, or a 40% decrease in eGFR. Predefined safety outcomes were serious infection, new diabetes, gastrointestinal hemorrhage, fracture/osteonecrosis, and cardiovascular events. The mean required follow-up was estimated to be 5 years. Results After randomization of 262 participants (mean age, 38.6 [SD, 11.1] years; 96 [37%] women; eGFR, 59.4 mL/min/1.73 m 2 ; urine protein excretion, 2.40 g/d) and 2.1 years’ median follow-up, recruitment was discontinued because of excess serious adverse events. Serious events occurred in 20 participants (14.7%) in the methylprednisolone group vs 4 (3.2%) in the placebo group ( P = .001; risk difference, 11.5% [95% CI, 4.8%-18.2%]), mostly due to excess serious infections (11 [8.1%] vs 0; risk difference, 8.1% [95% CI, 3.5%-13.9%]; P P = .02). Conclusions and Relevance Among patients with IgA nephropathy and proteinuria of 1 g/d or greater, oral methylprednisolone was associated with an increased risk of serious adverse events, primarily infections. Although the results were consistent with potential renal benefit, definitive conclusions about treatment benefit cannot be made, owing to early termination of the trial. Trial Registration clinicaltrials.gov Identifier:NCT01560052
308 citations
••
TL;DR: MRI is useful for detection of clinically significant disease at initial assessment of men considering active surveillance, but to use MRI as a monitoring tool in surveillance, it will be necessary to define both radiological significance and radiological progression.
306 citations
Authors
Showing all 7765 results
Name | H-index | Papers | Citations |
---|---|---|---|
Gordon B. Mills | 187 | 1273 | 186451 |
David A. Bennett | 167 | 1142 | 109844 |
Bruce R. Rosen | 148 | 684 | 97507 |
Robert Tibshirani | 147 | 593 | 326580 |
Steven A. Narod | 134 | 970 | 84638 |
Peter Palese | 132 | 526 | 57882 |
Gideon Koren | 129 | 1994 | 81718 |
John B. Holcomb | 120 | 733 | 53760 |
Julie A. Schneider | 118 | 492 | 56843 |
Patrick Maisonneuve | 118 | 582 | 53363 |
Mitch Dowsett | 114 | 478 | 62453 |
Ian D. Graham | 113 | 700 | 87848 |
Peter C. Austin | 112 | 657 | 60156 |
Sandra E. Black | 104 | 681 | 51755 |
Michael B. Yaffe | 102 | 379 | 41663 |