Hayden A.J.,Cancer Agency |
Catton C.,University of Toronto |
Pickles T.,University of British Columbia
External-beam radiotherapy and brachytherapy, widely utilized as curative treatment modalities for prostate cancer, have undergone significant clinical and technological advances in recent decades. Contemporary radiotherapy treatment algorithms use pretreatment prognostic factors to stratify patients into low-, intermediate-, and high-risk groups that correlate with both pathologic stage of disease and risk of recurrence after treatment. The use of risk groups and additional prognostic factors guide selection of the optimal treatment modalities for individual patients. Here, the roles of external-beam radiotherapy, brachytherapy, and neoadjuvant or adjuvant androgen deprivation therapy are discussed in that context. Additional prognostic factors for recurrence in the post-prostatectomy setting and the role of adjuvant and salvage radiation therapy are also reviewed. The risk-adaptive approach in radiotherapy for prostate cancer aims to optimize cancer control outcomes while minimizing the morbidity of treatment. © 2010 Multimed Inc. Source
A functional proteogenomic analysis of endometrioid and clear cell carcinomas using reverse phase protein array and mutation analysis: Protein expression is histotype-specific and loss of ARID1A/BAF250a is associated with AKT phosphorylation
Wiegand K.C.,University of British Columbia |
Hennessy B.T.,Beaumont Hospital |
Leung S.,Genetic Pathology Evaluation Center |
Wang Y.,University of British Columbia |
And 16 more authors.
Background: Ovarian cancer is now recognized as a number of distinct diseases primarily defined by histological subtype. Both clear cell ovarian carcinomas (CCC) and ovarian endometrioid carcinomas (EC) may arise from endometriosis and frequently harbor mutations in the ARID1A tumor suppressor gene. We studied the influence of histological subtype on protein expression with reverse phase protein array (RPPA) and assessed proteomic changes associated with ARID1A mutation/BAF250a expression in EC and CCC.Methods: Immunohistochemistry (IHC) for BAF250a expression was performed on 127 chemotherapy-naive ovarian carcinomas (33 CCC, 29 EC, and 65 high-grade serous ovarian carcinomas (HGSC)). Whole tumor lysates were prepared from frozen banked tumor samples and profiled by RPPA using 116 antibodies. ARID1A mutations were identified by exome sequencing, and PIK3CA mutations were characterized by MALDI-TOF mass spectrometry. SAM (Significance Analysis of Microarrays) was performed to determine differential protein expression by histological subtype and ARID1A mutation status. Multivariate logistic regression was used to assess the impact of ARID1A mutation status/BAF250a expression on AKT phosphorylation (pAKT). PIK3CA mutation type and PTEN expression were included in the model. BAF250a knockdown was performed in 3 clear cell lines using siRNA to ARID1A.Results: Marked differences in protein expression were observed that are driven by histotype. Compared to HGSC, SAM identified over 50 proteins that are differentially expressed in CCC and EC. These included PI3K/AKT pathway proteins, those regulating the cell cycle, apoptosis, transcription, and other signaling pathways including steroid hormone signaling. Multivariate models showed that tumors with loss of BAF250a expression showed significantly higher levels of AKT-Thr308 and AKT-Ser473 phosphorylation (p < 0.05). In 31 CCC cases, pAKT was similarly significantly increased in tumors with BAF250a loss on IHC. Knockdown of BAF250a by siRNA in three CCC cell lines wild type for ARID1A showed no increase in either pAKT-Thr308 or pAKT-S473 suggesting that pAKT in tumor tissues is indirectly regulated by BAF250a expression.Conclusions: Proteomic assessment of CCC and EC demonstrates remarkable differences in protein expression that are dependent on histotype, thereby further characterizing these cancers. AKT phosphorylation is associated with ARID1A/BAF250a deficient tumors, however in ovarian cancers the mechanism remains to be elucidated. © 2014 Wiegand et al.; licensee BioMed Central Ltd. Source
Eastern Canadian Colorectal Cancer Consensus Conference: Standards of care for the treatment of patients with rectal, pancreatic, and gastrointestinal stromal tumours and pancreatic neuroendocrine tumours
Di Valentin T.,The Ottawa Hospital Cancer Center |
Biagi J.,Queens University |
Bourque S.,Cancer Agency |
Butt R.,Capital Health |
And 29 more authors.
The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Halifax, Nova Scotia, October 20-22, 2011. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of rectal cancer, including pathology reporting, neoadjuvant systemic and radiation therapy, surgical techniques, and palliative care of rectal cancer patients. Other topics discussed include multidisciplinary cancer conferences, treatment of gastrointestinal stromal tumours and pancreatic neuroendocrine tumours, the use of FOLFIRINOX in pancreatic cancer, and treatment of stage II colon cancer. © 2013 Multimed Inc. Source
Yorukoglu D.,Simon Fraser University |
Yorukoglu D.,Massachusetts Institute of Technology |
Hach F.,Simon Fraser University |
Swanson L.,Simon Fraser University |
And 4 more authors.
Motivation: Computational identification of genomic structural variants via high-throughput sequencing is an important problem for which a number of highly sophisticated solutions have been recently developed. With the advent of high-throughput transcriptome sequencing (RNA-Seq), the problem of identifying structural alterations in the transcriptome is now attracting significant attention. In this article, we introduce two novel algorithmic formulations for identifying transcriptomic structural variants through aligning transcripts to the reference genome under the consideration of such variation. The first formulation is based on a nucleotide-level alignment model; a second, potentially faster formulation is based on chaining fragments shared between each transcript and the reference genome. Based on these formulations, we introduce a novel transcriptome-to-genome alignment tool, Dissect (DIScovery of Structural Alteration Event Containing Transcripts), which can identify and characterize transcriptomic events such as duplications, inversions, rearrangements and fusions. Dissect is suitable for whole transcriptome structural variation discovery problems involving sufficiently long reads or accurately assembled contigs. Results: We tested Dissect on simulated transcripts altered via structural events, as well as assembled RNA-Seq contigs from human prostate cancer cell line C4-2. Our results indicate that Dissect has high sensitivity and specificity in identifying structural alteration events in simulated transcripts as well as uncovering novel structural alterations in cancer transcriptomes. © The Author(s) 2012. Published by Oxford University Press. Source
MacAulay C.,Cancer Agency |
Poh C.F.,Cancer Agency |
Poh C.F.,University of British Columbia |
Guillaud M.,Cancer Agency |
And 4 more authors.
Journal of Biomedical Optics
The successful management of oral cancer depends upon early detection, which relies heavily on the clinician's ability to discriminate sometimes subtle alterations of the infrequent premalignant lesions from the more common reactive and inflammatory conditions in the oral mucosa. Even among experienced oral specialists this can be challenging, particularly when using new wide field-of-view direct fluorescence visualization devices clinically introduced for the recognition of at-risk tissue. The objective of this study is to examine if quantitative cytometric analysis of oral brushing samples could facilitate the assessment of the risk of visually ambiguous lesions. About 369 cytological samples were collected and analyzed: (1) 148 samples from pathology-proven sites of SCC, carcinoma in situ or severe dysplasia; (2) 77 samples from sites with inflammation, infection, or trauma, and (3) 144 samples from normal sites. These were randomly separated into training and test sets. The best algorithm correctly recognized 92.5% of the normal samples, 89.4% of the abnormal samples, 86.2% of the confounders in the training set as well as 100% of the normal samples, and 94.4% of the abnormal samples in the test set. These data suggest that quantitative cytology could reduce by more than 85% the number of visually suspect lesions requiring further assessment by biopsy. © 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). Source