Scott D.W.,British Columbia Cancer Agency |
Gascoyne R.D.,British Columbia Cancer Agency |
Gascoyne R.D.,University of British Columbia
Nature Reviews Cancer | Year: 2014
B cell lymphomas are cancers that arise from cells that depend on numerous highly orchestrated interactions with immune and stromal cells in the course of normal development. Despite the recent focus on dissecting the genetic aberrations within cancer cells, it has been increasingly recognized that tumour cells retain a range of dependence on interactions with the non-malignant cells and stromal elements that constitute the tumour microenvironment. A fundamental understanding of these interactions gives insight into the pathogenesis of most B cell lymphomas and, moreover, identifies novel therapeutic opportunities for targeting oncogenic pathways, both now and in the future. © 2014 Macmillan Publishers Limited.
Oh I.-H.,Catholic University of Korea |
Humphries R.K.,British Columbia Cancer Agency
Stem Cells | Year: 2012
Hematopoietic stem cells (HSCs) are characterized by their unique function to produce all lineages of blood cells throughout life. Such tissue-specific function of HSC is attributed to their ability to execute self-renewal and multilineage differentiation. Accumulating evidence indicates that the undifferentiated state of HSC is characterized by dynamic maintenance of chromatin structures and epigenetic plasticity. Conversely, quiescence, self-renewal, and differentiation of HSCs are dictated by complex regulatory mechanisms involving specific transcription factors and microenvironmental crosstalk between stem cells and multiple compartments of niches in bone marrows. Thus, multidimensional regulatory inputs are integrated into two opposing characters of HSCs-maintenance of undifferentiated state analogous to pluripotent stem cells but execution of tissue-specific hematopoietic functions. Further studies on the interplay of such regulatory forces as "cell fate determinant" will likely shed the light on diverse spectrums of tissue-specific stem cells. © AlphaMed Press.
Martinez-Gonzalez I.,British Columbia Cancer Agency |
Steer C.A.,University of British Columbia |
Takei F.,University of British Columbia
Trends in Immunology | Year: 2015
How allergens trigger the T helper 2 (Th2) response that characterizes allergic lung inflammation is not well understood. Epithelium-derived alarmins released after an allergen encounter activate the innate immune system, including group 2 innate lymphoid cells (ILC2s) which produce the type 2 interleukins IL-5 and IL-13. It has been recently shown that ILC2-derived cytokines are responsible not only for the innate responses underlying allergic inflammation but also for the initiation of the adaptive Th2 response. We review the role of lung ILC2s in the development of allergic inflammation and, in the context of recent findings, propose a common pathway wherein ILC2s, activated by the epithelium-derived cytokine IL-33, link the innate and the adaptive responses after allergen encounter in the lung. © 2015 Elsevier Ltd.
Aubert G.,British Columbia Cancer Agency
Progress in Molecular Biology and Translational Science | Year: 2014
Telomeres consist of repetitive DNA-protein complexes that cap the ends of vertebrate linear chromosomes. Their capping function and dynamics both with regard to structure and length are carefully orchestrated by many regulatory mechanisms and factors, with likely more yet to be described. Telomere shortening has been shown to be a major measurable molecular characteristic of aging of cells in vitro and in vivo and is thought to have evolved as a tumor protection mechanism in long-lived species. Regulators and modifiers of telomere dynamics and dynamics with age together with the consequences of telomere shortening and telomere dysfunction in the context of aging and aging-related disorders are discussed in this chapter. © 2014 Elsevier Inc.
Korbelik M.,British Columbia Cancer Agency
Photochemical and Photobiological Sciences | Year: 2011
The development of photodynamic therapy (PDT)-generated cancer vaccines is potentially one of the most significant achievements in the field of PDT. Employing vaccine protocols optimizes the capacity of PDT of inducing a strong immune response against treated tumor due to the establishment of highly favourable conditions for maximizing the avidity of the immune reaction while sustaining and prolonging its tumor-destroying attack. While the introduction of PDT vaccines into the clinics and testing on patients is still in a very early phase, much work can still be done on further improvement of the potency of PDT vaccines. Considerable advances can be expected by identifying the most effective adjuvants to be used with PDT vaccines, which will most likely be different with different types of cancerous lesions. © 2011 The Royal Society of Chemistry and Owner Societies.
Connors J.M.,British Columbia Cancer Agency
Blood | Year: 2015
Treatment of Hodgkin lymphoma is associated with 2 major types of risk: that the treatment may fail to cure the disease or that the treatment will prove unacceptably toxic. Careful assessment of the amount of the lymphoma (tumor burden), its behavior (extent of invasion or specific organ compromise), and host related factors (age; coincident systemic infection; and organ dysfunction, especially hematopoietic, cardiac, or pulmonary) is essential to optimize outcome. Elaborately assembled prognostic scoring systems, such as the International Prognostic Factors Project score, have lost their accuracy and value as increasingly effective chemotherapy and supportive care have been developed. Identification of specific biomarkers derived from sophisticated exploration of Hodgkin lymphoma biology is bringing promise of further improvement in targeted therapy in which effectiveness is increased at the same time off-target toxicity is diminished. Parallel developments in functional imaging are providing additional potential to evaluate the efficacy of treatment while it is being delivered, allowing dynamic assessment of risk during chemotherapy and adaptation of the therapy in real time. Risk assessment in Hodgkin lymphoma is continuously evolving, promising ever greater precision and clinical relevance. This article explores the past usefulness and the emerging potential of risk assessment for this imminently curable malignancy. © 2015 by The American Society of Hematology.
Connors J.M.,British Columbia Cancer Agency
Modern Pathology | Year: 2013
Optimal treatment of non-Hodgkin lymphoma depends on establishing an accurate diagnosis and determining the stage or anatomic extent of the lymphoma. With this information, the treating clinician can assign the lymphoma to a subgroup characterized by expected natural history: indolent, aggressive, acute leukemia-like or viral, which generally reflects the typical behavior of the disease unmodified by treatment and indicates the urgency with which intervention must be offered. Finally, a number of special circumstances and problems posed by specific lymphomas must be anticipated and the therapeutic plan altered to accommodate them. After primary treatment, special secondary events such as transformation to more aggressive histologic types must be recognized and the treatment plan must be altered to address these events. This article reviews standard diagnostic grouping of lymphomas, special problems encountered during primary diagnosis and subsequent clinical evolution and emphasizes the cooperative interaction between the hematopathologist and the treating clinician that underlies optimal management. © 2013 USCAP, Inc. All rights reserved.
Morrissy A.S.,British Columbia Cancer Agency |
Griffith M.,British Columbia Cancer Agency |
Marra M.A.,British Columbia Cancer Agency
Genome Research | Year: 2011
To analyze the relationship between antisense transcription and alternative splicing, we developed a computational approach for the detection of antisense-correlated exon splicing events using Affymetrix exon array data. Our analysis of expression data from 176 lymphoblastoid cell lines revealed that the majority of expressed sense-antisense genes exhibited alternative splicing events that were correlated to the expression of the antisense gene. Most of these events occurred in areas of sense-antisense (SAS) gene overlap, which were significantly enriched in both exons and nucleosome occupancy levels relative to nonoverlapping regions of the same genes. Nucleosome occupancy was highly correlated with Pol II abundance across overlapping regions and with concomitant increases in local alternative exon usage. These results are consistent with an antisense transcription-mediated mechanism of splicing regulation in normal human cells. A comparison of the prevalence of antisense-correlated splicing events between individuals of Mormon versus African descent revealed population-specific events that may indicate the continued evolution of new SAS loci. Furthermore, the presence of antisense transcription was correlated to alternative splicing across multiple metazoan species, suggesting that it may be a conserved mechanism contributing to splicing regulation. © 2011 by Cold Spring Harbor Laboratory Press.
Metasignal Therapeutics Inc. and British Columbia Cancer Agency | Date: 2012-10-24
The present disclosure provides methods for detecting the presence of a cancer stem cell and their use in cancer prognosis, evaluating risk of cancer metastasis, identifying or validating drug candidates, and determining treatment efficacy. It also provides kits useful for detecting the presence of cancer stem cells as well as methods of treating cancer using CAIX inhibitors.
Eaves C.J.,British Columbia Cancer Agency |
Humphries R.K.,British Columbia Cancer Agency
New England Journal of Medicine | Year: 2010
Wnt signaling is critical to leukemogenesis in two mouse models of acute myeloid leukemia. Copyright © 2010 Massachusetts Medical Society. All rights reserved.