Sunnybrook Health Sciences Centre

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.

Micro-RNA378 (miR-378) Regulates Ovarian Estradiol Production by Targeting Aromatase

Abstract: Estradiol is a steroid hormone that not only plays an important role in ovarian follicular development but also is associated with many reproductive disorders. Owing to the importance of aromatase in the production of estradiol, the regulation of aromatase gene expression at the transcriptional level has been an extensive area of study for over two decades. However, its regulation at the posttranscriptional level has remained unclear. Here, we show that micro-RNA378 (miR-378) is spatiotemporally expressed in porcine granulosa cells, the cells that generate estradiol in the ovary during follicular development, in an inverse manner compared with the expression of aromatase. In vitro overexpression and inhibition experiments revealed that aromatase expression, and therefore estradiol production, by granulosa cells, is posttranscriptionally down-regulated by miR-378. Furthermore, site-directed mutation studies identified two binding sites in the 3′-untranslated region (3′-UTR) of the aromatase coding sequence that are critical for the action of miR-378. Interestingly, overexpression of the aromatase 3′-UTR enhanced aromatase expression at the protein level in granulosa cells, possibly mediated by the binding of miR-378 within this region, thereby reducing the binding of this micro-RNA to the endogenous aromatase 3′-UTR.

Tracking the dynamics of circulating tumour cell phenotypes using nanoparticle-mediated magnetic ranking

Abstract: Profiling the heterogeneous phenotypes of rare circulating tumour cells (CTCs) in whole blood is critical to unravelling the complex and dynamic properties of these potential clinical markers. This task is challenging because these cells are present at parts per billion levels among normal blood cells. Here we report a new nanoparticle-enabled method for CTC characterization, called magnetic ranking cytometry, which profiles CTCs on the basis of their surface expression phenotype. We achieve this using a microfluidic chip that successfully processes whole blood samples. The approach classifies CTCs with single-cell resolution in accordance with their expression of phenotypic surface markers, which is read out using magnetic nanoparticles. We deploy this new technique to reveal the dynamic phenotypes of CTCs in unprocessed blood from mice as a function of tumour growth and aggressiveness. We also test magnetic ranking cytometry using blood samples collected from cancer patients.

Incidence of complications other than urinary incontinence or erectile dysfunction after radical prostatectomy or radiotherapy for prostate cancer: a population-based cohort study

Abstract: Summary Background Studies of complications resulting from surgery or radiotherapy for prostate cancer have mainly focused on incontinence and erectile dysfunction. We aimed to assess other important complications associated with these treatments for prostate cancer. Methods We did a population-based retrospective cohort study, in which we used administrative hospital data, physician billing codes, and cancer registry data for men who underwent either surgery or radiotherapy alone for prostate cancer between 2002 and 2009 in Ontario, Canada. We measured the 5-year cumulative incidence of five treatment-related complication endpoints: hospital admissions; urological, rectal, or anal procedures; open surgical procedures; and secondary malignancies. Findings In the 32 465 patients included in the study, the 5-year cumulative incidence of admission to hospital for a treatment-related complication was 22·2% (95% CI 21·7–22·7), but was 2·4% (2·2–2·6) for patients whose length of stay was longer than 1 day. The 5-year cumulative incidence of needing a urological procedure was 32·0% (95% CI 31·4–32·5), that of a rectal or anal procedure was 13·7% (13·3–14·1), and that of an open surgical procedure was 0·9% (0·8–1·1). The 5-year cumulative incidence of a second primary malignancy was 3·0% (2·6–3·5). These risks were significantly higher than were those of 32 465 matched controls with no history of prostate cancer. Older age and comorbidity at the time of index treatment were important predictors for a complication in all outcome categories, but the type of treatment received was the strongest predictor for complications. Patients who were given radiotherapy had higher incidence of complications for hospital admissions, rectal or anal procedures, open surgical procedures, and secondary malignancies at 5 years than did those who underwent surgery (adjusted hazard ratios 2·08–10·8, p Interpretation Complications after prostate cancer treatment are frequent and dependent on age, comorbidity, and the type of treatment. Patients and physicians should be aware of these risks when choosing treatment for prostate cancer, and should balance them with the clinical effectiveness of each therapy. Funding Ajmera Family Chair in Urologic Oncology.

How useful is preoperative imaging for tumor, node, metastasis (TNM) staging of gastric cancer? A meta-analysis

Abstract: Surgery is the fundamental curative option for gastric cancer patients. Imaging scans are routinely prescribed in an attempt to stage the disease prior to surgery. Consequently, the correlation between radiology exams and pathology is crucial for appropriate treatment planning. Systematic searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1998 to December 1, 2009. We calculated the accuracy, overstaging rate, understaging rate, Kappa statistic, sensitivity, and specificity for abdominal ultrasound (AUS), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) with respect to the gold standard (pathology). We also compared the performance of CT by detector number and image type. A meta-analysis was performed. For pre-operative T staging MRI scans had better performance accuracy than CT and AUS; CT scanners using ≥4 detectors and multi-planar reformatted (MPR) images had higher staging performances than scanners with <4 detectors and axial images only. For pre-operative N staging PET had the lowest sensitivity, but the highest specificity among modalities; CT performance did not significantly differ by detector number or addition of MPR images. For pre-operative M staging performance did not significantly differ by modality, detector number, or MPR images. The agreement between pre-operative TNM staging by imaging scans and post-operative staging by pathology is not perfect and may affect treatment decisions. Operator dependence and heterogeneity of data may account for the variations in staging performance. Physicians should consider this discrepancy when creating their treatment plans.

The fall and rise of carotid endarterectomy in the United States and Canada.

Abstract: Background Randomized clinical trials have demonstrated the efficacy of carotid endarterectomy in the prevention of stroke when the procedure is performed in regional centers of surgical excellence. However, the relative effects of these studies on the rates of carotid endarterectomy in the United States and Canada have been unclear. Methods We calculated the annual rate of carotid endarterectomy in the U.S. states of California and New York and in the Canadian province of Ontario from 1983 through 1995. We also studied whether patients in the early 1990s were selectively referred to hospitals with high volumes of procedures and historically low in-hospital mortality rates. Results Rates of carotid endarterectomy fell in all three regions from 1984 to 1989 (from 126 to 66 per 100,000 adults 40 years of age or older in California, from 65 to 40 per 100,000 in New York, and from 40 to 15 per 100,000 in Ontario), after the publication of studies demonstrating that the rates of complications of carotid endart...