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Sierra Pellizzari,1 Harjot Athwal,1 Anne Claudine Bonvissuto,1,2 Armen Parsyan1– 4 1Department of Anatomy and Cell Biology, Western University, London, ON, Canada; 2Verspeeten Family Cancer Centre, London Health Sciences Centre, London, ON, Canada; 3Department of Oncology, Western University, London, ON, Canada; 4Department of Surgery, St Joseph’s Health Care and London Health Sciences Centre, Western University, London, ON, CanadaCorrespondence: Armen Parsyan, Department of Surgery, St Joseph’s Health Care London, Room D1-104, 268 Grosvenor Street, London, ON, N6A 4V2, Canada, Tel +1-519-646-4831, Email aparsyan@uwo.caAbstract: Breast cancer is a leading cause of cancer-related deaths in females. Triple-negative breast cancer (TNBC) subtype is the most aggressive form of breast cancer that lacks biomarkers and effective targeted therapies. Its high degree of heterogeneity as well as innate and acquired resistance to treatment creates further barriers in achieving positive clinical outcomes in TNBC. Thus, development of novel treatment approaches in TNBC is of high clinical significance. Multimodality approaches with targeted agents and radiotherapy (RT) are promising for increasing efficacy of treatment and circumventing resistance. Here we examined anticancer effects of the Aurora Kinase B (AURKB) inhibitor AZD1152 as a single agent and in combination with RT using various TNBC cell lines, MDA-MB-468, MDA-MB-231 and SUM-159. We observed that AZD1152 alone effectively inhibited colony formation in TNBC cell lines. The combination of AZD1152 at IC50 concentrations together with ionizing radiation further reduced colony formation as compared to the single agent treatment. Our data support the notion that inhibition of the AURKB pathway is a promising strategy for treatment and radiosensitization of TNBC and warrants further translational studies.Plain Language Summary: Breast cancer is a leading cause of cancer death in women globally. The triple negative breas

Breast cancer remains one of the leading causes of cancer morbidity and mortality. Despite significant advances in treatment of breast cancer a substantial proportion of women affected by this disease succumb to it. Survival of patients with advanced disease, chemoresistant tumors or a suboptimal response to endocrine therapy is significantly shortened. Hence, further understanding of disease pathogenesis is required to enhance the arsenal of approaches to cure this deadly ailment. Recent advances in biochemistry, molecular cell biology and cancer research highlighted the importance of dysregulation of protein synthesis, translation, in the development and progression of tumors. This dysregulation appears to take place at an early stage of translation, called translation initiation, that is a highly controlled and rate-limiting step of the protein synthesis. In this chapter we summarize decades of knowledge accumulated in regards to the role of translation and its regulation in the development and progression of breast cancer. We then extensively discuss applications of this knowledge in diagnosis and treatment of breast cancer., SCOPUS: ch.b, info:eu-repo/semantics/published

Diversity is one of the most remarkable features of living organisms. Current assessments of eukaryote biodiversity reaches 1.5 million species, but the true figure could be several times that number. Diversity is ingrained in all stages and echelons of life, namely, the occupancy of ecological niches, behavioral patterns, body plans and organismal complexity, as well as metabolic needs and genetics. In this review, we will discuss that diversity also exists in a key biochemical process, translation, across eukaryotes. Translation is a fundamental process for all forms of life, and the basic components and mechanisms of translation in eukaryotes have been largely established upon the study of traditional, so-called model organisms. By using modern genome-wide, high-throughput technologies, recent studies of many nonmodel eukaryotes have unveiled a surprising diversity in the configuration of the translation apparatus across eukaryotes, showing that this apparatus is far from being evolutionarily static. For some of the components of this machinery, functional differences between different species have also been found. The recent research reviewed in this article highlights the molecular and functional diversification the translational machinery has undergone during eukaryotic evolution. A better understanding of all aspects of organismal diversity is key to a more profound knowledge of life.

Candotti and colleagues (1) reported the prevalence of a third strain of human erythrovirus, genotype 3 (V9), in the Ghanaian population and, in part, concluded that a genotype 1 (B19)-based assay failed to detect genotype 3 immunoglobulin G (IgG) in 38.5% of Ghanaian samples containing genotype 3 antibodies. We disagree with this conclusion for the following reasons.