REVIEW: Synthetic Lethality and Cancer

A synthetic lethal interaction occurs between two genes when the perturbation of either gene alone is viable but the perturbation of both genes simultaneously results in the loss of viability. Key to exploiting synthetic lethality in cancer treatment are the identification and the mechanistic characterization of robust synthetic lethal genetic interactions. Advances in next-generation sequencing technologies are enabling the identification…
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Mutations in amyloid β precursor protein (APP) gene alter APP processing, either causing familial Alzheimer’s Disease (AD) or protecting against dementia. Under normal conditions beta-site APP cleaving enzyme 1 (BACE1) cleaves APP at minor Asp1 site to generate C99 for amyloid β protein (Aβ) production, and predominantly at major Glu11 site to generate C89, resulting in truncated Aβ production. We discovered that…
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A Heme-Dependent Enzyme Forms the Nitrogen-Nitrogen Bond in Piperazate

Molecules containing a nitrogen-nitrogen (N-N) linkage have a variety of structures and biological activities; however, no enzyme has yet been demonstrated to catalyze N-N bond formation in an organic molecule. Here we report that the heme-dependent enzyme KtzT from Kutzneria sp. 744 catalyzes N-N bond formation in the biosynthesis of piperazate, a building block for nonribosomal peptides.
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PD-L1 and Intratumoral Immune Response in Breast Cancer

PD-L1 is thought to play an important role in the antitumor immune response. In this study, we investigated the expression of PD-L1 within breast tumor subsets to better define its prognostic significance. METHODS: Immunohistochemistry was performed to determine PD-L1 tumor cell expression and to enumerate CD8, CD4 and CD68 tumor-infiltrating leucocytes (TIL) in a cohort of 443 breast cancers categorized…
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Alternative transcription start site (TSS) usage plays important roles in transcriptional control of mammalian gene expression. The growing interest in alternative TSSs and their role in genome diversification spawned many single-gene studies on differential usages of tissue-specific or temporal-specific alternative TSSs. However, exploration of the switching usage of alternative TSS usage on a genomic level, especially in the central nervous…
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The separation of sarcomatoid and desmoplastic malignant mesotheliomas from sarcomatoid carcinomas of the lung metastatic to the pleura may be difficult, since both types of tumor can be morphologically similar and are frequently positive only for pan-keratin. GATA binding protein 3 (GATA3) is most commonly used as an immunohistochemical marker of breast and urothelial carcinoma, but is also known to…
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Read the Publication  This week we profile a recent publication in Oncotarget from the laboratory of Dr. Xiaoyan Jiang (centre) at the Terry Fox Laboratories. Can you provide a brief overview of your lab’s current research focus? The focus of our translational leukemia research is to identify key molecules and pathways that will lead to new, rationally designed, more effective,…
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The effect of age at first dose on the immunogenicity of a two-dose pediatric schedule of Measles-Mumps-Rubella (MMR) or MMR-Varicella (MMRV) vaccines was assessed in children born to mostly vaccinated mothers. Immunogenicity data among children given their first measles vaccine dose between 11 and 22 months of age were pooled from five randomized controlled trials conducted in Europe and the…
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Every day, 43 children are diagnosed with cancer in North America. Although there have been clear improvements in the treatment of many forms of childhood cancer, the outcome for patients with recurrent or metastatic disease remains dismal and almost unchanged for decades. Moreover, current therapies have very serious side effects on the developing child. This is particularly the case for aggressive childhood cancers such as neuroblastoma, where it is essential to discover targetable alterations typical of cancer cells but which spare normal cells.
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Copaxone is an efficacious and safe therapy that has demonstrated clinical benefit for over two decades in patients with relapsing forms of multiple sclerosis (MS). On an individual level, patients show variability in their response to Copaxone, with some achieving significantly higher response levels. The involvement of genes (e.g., HLA-DRB1*1501) with high inter-individual variability in Copaxone’s mechanism of action (MoA)…
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