211 results on '"Sykes, Jenna"'
Search Results
202. The changing epidemiology and demography of cystic fibrosis.
- Author
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Stephenson AL, Stanojevic S, Sykes J, and Burgel PR
- Subjects
- Adolescent, Adult, Canada, Child, Child, Preschool, Cross-Cultural Comparison, Cross-Sectional Studies, Cystic Fibrosis mortality, Cystic Fibrosis therapy, Europe, Humans, Infant, Infant, Newborn, Interdisciplinary Communication, Intersectoral Collaboration, Neonatal Screening, Registries, United States, Young Adult, Cystic Fibrosis epidemiology, Demography, Life Expectancy
- Abstract
Once considered a pediatric disease with a poor prognosis, individuals born with cystic fibrosis (CF) today can expect to live well into adulthood. The implementation of multidisciplinary care, novel treatments and newborn screening has resulted in the rapid evolution in the demographics of the CF population. The purpose of this review is to highlight the evolving epidemiology and demographics of the CF population internationally., (Copyright © 2017. Published by Elsevier Masson SAS.)
- Published
- 2017
- Full Text
- View/download PDF
203. Determination of the Association Between T2-weighted MRI and Gleason Sub-pattern: A Proof of Principle Study.
- Author
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Downes MR, Gibson E, Sykes J, Haider M, van der Kwast TH, and Ward A
- Subjects
- Adult, Aged, Biopsy, Humans, Male, Middle Aged, Neoplasm Grading, Prostatectomy, Prostatic Neoplasms surgery, Magnetic Resonance Imaging, Prostatic Neoplasms diagnostic imaging, Prostatic Neoplasms pathology
- Abstract
Rationale and Objectives: The study aimed to determine the relationship between T2-weighted magnetic resonance imaging (MRI) signal and histologic sub-patterns in prostate cancer areas with different Gleason grades., Materials and Methods: MR images of prostates (n = 25) were obtained prior to radical prostatectomy. These were processed as whole-mount specimens with tumors and the peripheral zone was annotated digitally by two pathologists. Gleason grade 3 was the most prevalent grade and was subdivided into packed, intermediate, and sparse based on gland-to-stroma ratio. Large cribriform, intraductal carcinoma, and small cribriform glands (grade 4 group) were separately annotated but grouped together for statistical analysis. The log MRI signal intensity for each contoured region (n = 809) was measured, and pairwise comparisons were performed using the open-source software R version 3.0.1., Results: Packed grade 3 sub-pattern has a significantly lower MRI intensity than the grade 4 group (P < 0.00001). Sparse grade 3 has a significantly higher MRI intensity than the packed grade 3 sub-pattern (P < 0.0001). No significant difference in MRI intensity was observed between the Gleason grade 4 group and the sparse sub-pattern grade 3 group (P = 0.54). In multivariable analysis adjusting for peripheral zone, the P values maintained significance (packed grade 3 group vs grade 4 group, P < 0.001; and sparse grade 3 sub-pattern vs packed grade 3 sub-pattern, P < 0.001)., Conclusions: This study demonstrated that T2-weighted MRI signal is dependent on histologic sub-patterns within Gleason grades 3 and 4 cancers, which may have implications for directed biopsy sampling and patient management., (Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
204. Cetuximab Inhibits T790M-Mediated Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in a Lung Adenocarcinoma Patient-Derived Xenograft Mouse Model.
- Author
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Martin P, Stewart E, Pham NA, Mascaux C, Panchal D, Li M, Kim L, Sakashita S, Wang D, Sykes J, Friess T, Shepherd FA, Liu G, and Tsao MS
- Subjects
- Adenocarcinoma pathology, Adenocarcinoma of Lung, Animals, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Carcinoma, Non-Small-Cell Lung pathology, Cetuximab administration & dosage, Drug Resistance, Neoplasm drug effects, Drug Resistance, Neoplasm genetics, Erlotinib Hydrochloride administration & dosage, Female, Humans, Lung Neoplasms pathology, Mice, Middle Aged, Mutation, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors pharmacology, Quinazolinones administration & dosage, Random Allocation, Signal Transduction drug effects, Time Factors, Xenograft Model Antitumor Assays, Adenocarcinoma drug therapy, Antineoplastic Combined Chemotherapy Protocols pharmacology, Carcinoma, Non-Small-Cell Lung drug therapy, ErbB Receptors genetics, Lung Neoplasms drug therapy
- Abstract
Background: The epidermal growth factor receptor (EGFR) kinase domain T790M (amino acid substitution at position 790 in EGFR from threonine [T] to methionine [M]) mutation in non-small-cell lung cancer (NSCLC) results in resistance to EGFR tyrosine kinase inhibitors (TKIs). We used a patient-derived tumor xenograft (PDX) model containing an EGFR exon 19 deletion/T790M mutation to assess response to the EGFR-directed antibody cetuximab. Changes in the EGFR signaling pathway and ligand expression after treatment were investigated., Methods: PDX were randomized into control and treatment arms. Pharmacodynamic studies were performed at 2 and 24 hours and at 4 days after a single administration of cetuximab, erlotinib, or dacomitinib. Changes in the EGFR signaling pathway were assessed using Western blot analysis, and baseline mRNA expression of EGFR ligands using microarray analysis. Relative changes after treatment were assessed using quantitative polymerase chain reaction., Results: The xenograft showed a dramatic response to cetuximab. A complete reduction of total EGFR and phosphorylated EGFR occurred after cetuximab treatment. The PDX had increased baseline levels of heparin-binding epidermal growth factor-like growth factor (HB-EGF) compared with other PDX models with or without EGFR mutations. Amphiregulin was significantly reduced 2 hours after treatment with cetuximab. Compared with control mice, cetuximab- and EGFR-TKI-treated mice had significantly reduced HB-EGF gene expression at 2 hours, however, by day 4 the level of HB-EGF expression was higher. The effect of cetuximab compared with EGFR TKI on HB-EGF gene expression levels differed significantly at 2 and 24 hours but not at 4 days., Conclusion: We showed a dramatic tumor response with cetuximab in an exon 19 deletion/T790M EGFR mutant lung adenocarcinoma PDX model, which suggests a role for the autocrine feedback loop in the mutant EGFR signaling pathway. Further investigation using cetuximab in NSCLC with T790M mutation is warranted., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
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205. A standardized approach to estimating survival statistics for population-based cystic fibrosis registry cohorts.
- Author
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Sykes J, Stanojevic S, Goss CH, Quon BS, Marshall BC, Petren K, Ostrenga J, Fink A, Elbert A, and Stephenson AL
- Subjects
- Age Factors, Canada epidemiology, Humans, Life Tables, Proportional Hazards Models, Cystic Fibrosis mortality, Registries standards, Survival Analysis
- Abstract
Objectives: Our objective was to quantify the effect of different statistical techniques, inclusion/exclusion criteria, and missing data on the predicted median survival age., Study Design and Setting: Using the Canadian cystic fibrosis registry (CCFR), the median age of survival was calculated using both the Cox proportional hazards (PH) and the life-table methods. Through simulations, we examined how the median age of survival would change when: (1) patients were excluded, (2) death dates were inaccurate, (3) patients were lost to follow-up, (4) entire years with no clinic visits were excluded even if the patient had a visit in subsequent years, and (5) censoring patients at their date of transplant. Simulations were run assuming 5-35% of data were affected by each scenario., Results: Over the period 2009-2013, there were 4,666 individuals in the CCFR with 240 deaths. The observed median age of survival calculated by the Cox PH method was 50.9 [95% confidence interval (CI): 47.4, 54.3] and 50.5 from the life-table method (95% CI: 47.5, 53.5). Censoring patients at their transplant date overestimated the median age of survival by 7.2 years (58.1; 95% CI: 53.3, 64.7). Simulations determined that by missing just 15% of deaths, the median age of survival can be overestimated by 3.5 years (54.4; 95% CI: 54.2, 56.1), and having 25% of patients lost to follow-up can underestimate the median age of survival by 3.3 years (47.6; 95% CI: 46.8, 47.7)., Conclusion: We present several recommendations to assist national cystic fibrosis registries in calculating and reporting the median age of survival in a standardized fashion. It is imperative to state the statistical method used as well as the proportion lost to follow-up and the treatment of missing data and transplanted patients. Registries must be diligent in their data collection as incomplete data can lead to overestimation and underestimation of survival., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
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206. NBN gain is predictive for adverse outcome following image-guided radiotherapy for localized prostate cancer.
- Author
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Berlin A, Lalonde E, Sykes J, Zafarana G, Chu KC, Ramnarine VR, Ishkanian A, Sendorek DH, Pasic I, Lam WL, Jurisica I, van der Kwast T, Milosevic M, Boutros PC, and Bristow RG
- Subjects
- Biomarkers, Tumor biosynthesis, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Cell Cycle Proteins biosynthesis, Cell Cycle Proteins metabolism, Comparative Genomic Hybridization, DNA Damage genetics, Disease-Free Survival, Genomic Instability, Humans, Male, Nuclear Proteins biosynthesis, Nuclear Proteins metabolism, Precision Medicine methods, Predictive Value of Tests, Prostatectomy, Prostatic Neoplasms metabolism, Prostatic Neoplasms surgery, Radiation Tolerance genetics, Radiotherapy, Image-Guided adverse effects, Radiotherapy, Image-Guided methods, Treatment Outcome, Cell Cycle Proteins genetics, Nuclear Proteins genetics, Prostatic Neoplasms genetics, Prostatic Neoplasms radiotherapy
- Abstract
Despite the use of clinical prognostic factors (PSA, T-category and Gleason score), 20-60% of localized prostate cancers (PCa) fail primary local treatment. Herein, we determined the prognostic importance of main sensors of the DNA damage response (DDR): MRE11A, RAD50, NBN, ATM, ATR and PRKDC. We studied copy number alterations in DDR genes in localized PCa treated with image-guided radiotherapy (IGRT; n=139) versus radical prostatectomy (RadP; n=154). In both cohorts, NBN gains were the most frequent genomic alteration (14.4 and 11% of cases, respectively), and were associated with overall tumour genomic instability (p<0.0001). NBN gains were the only significant predictor of 5yrs biochemical relapse-free rate (bRFR) following IGRT (46% versus 77%; p=0.00067). On multivariate analysis, NBN gain remained a significant independent predictor of bRFR after adjusting for known clinical prognostic variables (HR=3.28, 95% CI 1.56-6.89, Wald p-value=0.0017). No DDR-sensing gene was prognostic in the RadP cohort. In vitro studies correlated NBN gene overexpression with PCa cells radioresistance. In conclusion, NBN gain predicts for decreased bRFR in IGRT, but not in RadP patients. If validated independently, Nibrin gains may be the first PCa predictive biomarker to facilitate local treatment decisions using precision medicine approaches with surgery or radiotherapy.
- Published
- 2014
- Full Text
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207. Sample features associated with success rates in population-based EGFR mutation testing.
- Author
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Shiau CJ, Babwah JP, da Cunha Santos G, Sykes JR, Boerner SL, Geddie WR, Leighl NB, Wei C, Kamel-Reid S, Hwang DM, and Tsao MS
- Subjects
- Biopsy, Needle, Canada, Carcinoma, Non-Small-Cell Lung chemistry, Carcinoma, Non-Small-Cell Lung pathology, Cytological Techniques, DNA Mutational Analysis, Exons, Female, Genetic Testing, Humans, Lung Neoplasms chemistry, Lung Neoplasms pathology, Male, Nuclear Proteins analysis, Pneumonectomy, Retrospective Studies, Thyroid Nuclear Factor 1, Transcription Factors analysis, Base Sequence, Carcinoma, Non-Small-Cell Lung genetics, ErbB Receptors genetics, Lung Neoplasms genetics, Sequence Deletion
- Abstract
Introduction: Epidermal growth factor receptor (EGFR) mutation testing has become critical in the treatment of patients with advanced non-small-cell lung cancer. This study involves a large cohort and epidemiologically unselected series of EGFR mutation testing for patients with nonsquamous non-small-cell lung cancer in a North American population to determine sample-related factors that influence success in clinical EGFR testing., Methods: Data from consecutive cases of Canadian province-wide testing at a centralized diagnostic laboratory for a 24-month period were reviewed. Samples were tested for exon-19 deletion and exon-21 L858R mutations using a validated polymerase chain reaction method with 1% to 5% detection sensitivity., Results: From 2651 samples submitted, 2404 samples were tested with 2293 samples eligible for analysis (1780 histology and 513 cytology specimens). The overall test-failure rate was 5.4% with overall mutation rate of 20.6%. No significant differences in the failure rate, mutation rate, or mutation type were found between histology and cytology samples. Although tumor cellularity was significantly associated with test-success or mutation rates in histology and cytology specimens, respectively, mutations could be detected in all specimen types. Significant rates of EGFR mutation were detected in cases with thyroid transcription factor (TTF)-1-negative immunohistochemistry (6.7%) and mucinous component (9.0%)., Conclusions: EGFR mutation testing should be attempted in any specimen, whether histologic or cytologic. Samples should not be excluded from testing based on TTF-1 status or histologic features. Pathologists should report the amount of available tumor for testing. However, suboptimal samples with a negative EGFR mutation result should be considered for repeat testing with an alternate sample.
- Published
- 2014
- Full Text
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208. Active breathing control for patients receiving mediastinal radiation therapy for lymphoma: Impact on normal tissue dose.
- Author
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Charpentier AM, Conrad T, Sykes J, Ng A, Zhou R, Parent A, Coolens C, Tsang RW, Gospodarowicz MK, Sun A, and Hodgson DC
- Subjects
- Adolescent, Adult, Aged, Dose Fractionation, Radiation, Female, Humans, Inhalation, Lymphoma diagnostic imaging, Male, Middle Aged, Radiography, Retrospective Studies, Young Adult, Breathing Exercises methods, Lymphoma radiotherapy, Radiotherapy Planning, Computer-Assisted methods
- Abstract
Purpose: Active breathing control (ABC) is emerging as a tool to reduce heart and lung dose for lymphoma patients receiving mediastinal radiation therapy (RT). The objective of this study was to report our early institutional experience with this technique, with emphasis on quantifying the changes in normal tissue dose and exploring factors that could be used to select patients with the greatest benefit., Methods and Materials: Patients receiving mediastinal involved-field RT (IFRT) for lymphoma were eligible. The ABC was performed using a moderate deep-inspiration breath-hold (mDIBH) technique. All patients were replanned with free-breathing (FB) computed tomographic data sets and comparisons of lung, cardiac, and female breast tissue doses were made between mDIBH and FB plans. Logistic regression models were used to identify factors associated with improvement in mean lung and heart dose with mDIBH., Results: Forty-seven patients were analyzed; the majority (87.2%) had Hodgkin lymphoma. Median prescribed dose was 30 Gy (range, 20-36 Gy), with 78.7% of cases being treated with parallel-opposed beams. The use of mDIBH significantly improved average mean lung dose (FB: 11.0 Gy; mDIBH: 9.5 Gy; P < .0001), lung V20 (28% vs 22%; P < .0001), and mean heart dose (14.3 Gy vs 11.8 Gy; P = .003), but increased the mean breast dose (FB: 3.0 Gy; mDIBH 3.6 Gy; P = .0005). The magnitude of diaphragmatic excursion on the inhale scan was significantly associated with dosimetric improvement in both heart and lung dose with mDIBH., Conclusions: Mediastinal IFRT for lymphoma delivered with mDIBH can significantly reduce lung and heart dose compared with FB, although not for all patients, and may increase breast dose in females. Its implementation is achievable in both adult and pediatric populations. Further work is necessary to better predict which patients benefit from this technique., (© 2014.)
- Published
- 2014
- Full Text
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209. Prognostic utility of cell cycle progession score in men with prostate cancer after primary external beam radiation therapy. In regard to Freedland et al.
- Author
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Berlin A, Sykes J, Dal Pra A, Catton C, Van der Kwast T, and Bristow RG
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- Humans, Male, Genes, cdc, Neoplasm Recurrence, Local genetics, Prostatic Neoplasms genetics, RNA, Messenger analysis
- Published
- 2014
- Full Text
- View/download PDF
210. Validation of a histology-independent prognostic gene signature for early-stage, non-small-cell lung cancer including stage IA patients.
- Author
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Der SD, Sykes J, Pintilie M, Zhu CQ, Strumpf D, Liu N, Jurisica I, Shepherd FA, and Tsao MS
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- Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung pathology, Female, Gene Expression Regulation, Neoplastic, Humans, Lung Neoplasms drug therapy, Lung Neoplasms pathology, Male, Middle Aged, Neoplasm Staging, Prognosis, Carcinoma, Non-Small-Cell Lung genetics, Gene Expression Profiling, Lung Neoplasms genetics
- Abstract
Background: Patients with early-stage non-small-cell lung carcinoma (NSCLC) may benefit from treatments based on more accurate prognosis. A 15-gene prognostic classifier for NSCLC was identified from mRNA expression profiling of tumor samples from the NCIC CTG JBR.10 trial. In this study, we assessed its value in an independent set of cases., Methods: Expression profiling was performed on RNA from frozen, resected tumor tissues corresponding to 181 stage I and II NSCLC cases collected at University Health Network (UHN181). Kaplan-Meier methodology was used to estimate 5-year overall survival probabilities, and the prognostic effect of the classifier was assessed using the log-rank test. A Cox proportional hazards model evaluated the signature's effect adjusting for clinical prognostic factors., Results: Expression data of the 15-gene classifier stratified UHN181 cases into high- and low-risk subgroups with significantly different overall survival (hazard ratio [HR] = 1.92; 95% confidence interval [CI], 1.15-3.23; p = 0.012). In a subgroup analysis, this classifier predicted survival in 127 stage I patients (HR = 2.17; 95% CI, 1.12-4.20; p = 0.018) and the smaller subgroup of 48 stage IA patients (HR = 5.61; 95% CI, 1.19-26.45; p = 0.014). The signature was prognostic for both adenocarcinoma and squamous cell carcinoma cases (HR = 1.76, p = 0.058; HR = 4.19, p = 0.045, respectively)., Conclusion: The prognostic accuracy of a 15-gene classifier was validated in an independent cohort of 181 early-stage NSCLC samples including stage IA cases and in different NSCLC histologic subtypes.
- Published
- 2014
- Full Text
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211. Length matters in prostate cancer.
- Author
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Siadat F, Sykes J, and Van der Kwast TH
- Subjects
- Humans, Male, Biopsy, Large-Core Needle methods, Biopsy, Large-Core Needle standards, Prostate pathology, Prostatic Neoplasms diagnosis
- Published
- 2013
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