TIM-3 Expression in Breast Cancer

TIM-3 is an immune biomarker that is currently targeted by new immunotherapy drugs. Our study reports the first large-scale evaluation of TIM-3 expression based on our examination of nearly 4,000 breast cancers from the province of British Columbia. We report that TIM3 is present in more than a quarter of patients with a basal-like breast cancer, an aggressive cancer type with no targeted therapy. The findings from our publication imply that patients with basal-like breast cancers can potentially be amenable to immunotherapies targeting TIM-3.
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Each year, about 1 in 10 babies worldwide are born before the pregnancy has reached full term. Using samples of tissue collected from donated placentas from preterm births with and without inflammation, we examined DNA methylation, a chemical mark on DNA that is associated with how genes are turned on and off in the cell. We were able to identify unique DNA methylation changes in the placenta associated with inflammation in preterm birth pregnancies.
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Genomic rearrangements in the MYC locus occur in ∼12% of lymphomas with diffuse large B-cell lymphoma (DLBCL) morphology and are associated with inferior outcome. Previous studies exploring MYC rearrangements have primarily used fluorescence in situ hybridization (FISH) assays to characterize break-apart status but have rarely examined breakpoint location, and in some cases have not examined partner identity. We performed targeted sequencing of MYC, BCL2, BCL6, and the…
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Calmodulin (CaM) represents one of the most conserved proteins among eukaryotes and is known to bind and modulate more than a 100 targets. Recently, several disease-associated mutations have been identified in the CALM genes that are causative of severe cardiac arrhythmia syndromes. Although several mutations have been shown to affect the function of various cardiac ion channels, direct structural insights into any…
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Phenotype-Independent DNA Methylation Changes in Prostate Cancer

Our study found that many of the common DNA methylation alterations found in prostate cancer are present in luminal cells from both cancer and normal tissues. These changes are not necessarily cancer-specific, and are likely due to the bias associated with analyzing tissues in bulk, where most cancer cells have luminal-like features. We derived two cancer-specific and phenotype-independent DNA methylation signatures: one specific to prostate cancer luminal cells, and one composed of alterations present in both luminal and basal cancer cells.
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Intracellular nucleotide‐binding (NB) and leucine‐rich repeat (NLR) proteins function as immune receptors to recognize effectors from pathogens. They often guard host proteins that are the direct targets of those effectors. Recent findings revealed that a typical NLR sometimes cooperates with another atypical NLR for effector recognition. Here, by using CRISPR/Cas9 gene editing method, knockout analysis and biochemical assays, we uncovered…
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HIV isolates are extremely genetically variable (the HIV-1 group M “pandemic" isolates can be classified into 9 subtypes and nearly 100 circulating recombinant forms), and our knowledge of immune-driven escape pathways and their functional costs is largely limited to HIV subtype B, and to a lesser extent C. Our study represents the first characterization of immune-driven adaptation pathways in HIV subtypes A1 and D, which dominate in East Africa, and the first statistically rigorous characterization...
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Salt has long been an enigma in the taste field, because it elicits different responses depending on concentration. We love a little bit of salt (French fries, etc.) but really don’t like it at high concentrations (think about swallowing sea water). It has been proposed that this dual effect arises from activation of two taste cell types – a ‘low salt’ cell that produces attraction, and a ‘high salt’ cell that produces aversion. What we show is that in flies, salt affects all five...
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In this manuscript we describe a novel approach in studying cancer biology – we explored genetic/epigenetic programming in fetal tissues to reveal extinct cellular processes that, when “re-awakened” in adult tissues, alters and ultimately disrupts the function of cancer stem cells. We happened upon this idea from work by Connie Eaves and others who had previously shown that the behavior of fetal hematopoietic stem cells...
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It has been well-established that aging in both humans and animals is associated with impairments in learning and memory. However, it is less clear how aging might affect integration of different memories to guide more complex forms of cognition (sometimes referred to as “executive functions”). In this study, we used aged rats to model these deficits, and found that aging was associated with impairments in different executive functions that require flexible use of different types of memories and are mediated by the frontal lobes of the brain.
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