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PURPOSE: Breast cancer is the most diagnosed cancer in women with chemotherapy being a common treatment. Toxicities due to chemotherapy can result in dose reduction, delay, and early cessation of treatment, which along with causing distress for individuals during their cancer treatment might also reduce the therapeutic effect. The purpose of this systematic review is to examine the role of body composition on chemotherapy toxicities in women with breast cancer. METHODS: A systematic search of the literature was completed on electronic databases Pubmed, Embase, CINHAHL, and Cochrane. Studies were included if the direct effect of body composition on chemotherapy toxicities was reported and excluded if body composition could not be isolated. A critical appraisal of the studies included was performed using McMasters University Critical Review Form for Quantitative Studies. RESULTS: Eleven studies were included with a total of 2881 female participants. All studies reported significant relationships between body composition and chemotherapy toxicities; however, individual parameters differed between the studies. Adding to the heterogeneity, different thresholds were reported to determine both sarcopenia and myosteatosis, making it difficult to identify a common finding. CONCLUSION: This review suggests that body composition may be an important factor in predicting the severity of chemotherapy toxicities during treatment for breast cancer; however, the lack of international consensus as to thresholds in the literature for sarcopenia and myosteatosis may result in bias. The review supports the need for further prospective studies, allowing for more robust, pre-determined data collection, to better understand the implications of body composition on toxicities and benefits of using body composition to individualize chemotherapy dosing. IMPLICATIONS FOR CANCER SURVIVORS: Toxicities due to chemotherapy can result in treatment being unable to be completed as planned, potentially resulting in poorer survival outcomes. Improved knowledge in this area may give rise to a more reliable way of individualizing chemotherapy dosage to help mitigate this risk.
RESUMO
Some bacterial plasmids carry antibiotic resistance genes and replicate by an asymmetric, rolling circle mechanism, in which replication of the two strands is not concurrent. Initiation of this replication occurs via an initiator protein that nicks one DNA strand at the double-stranded origin of replication. In this work, RepD protein from the staphylococcal plasmid pC221 carries this function and allows PcrA helicase to bind and begin unwinding the plasmid DNA. This work uses whole plasmid constructs as well as oligonucleotide-based mimics of parts of the origin to examine the initiation reaction. It investigates the phenomenon that nicking, although required to open a single-stranded region at the origin and so allow PcrA to bind, is not required for another function of RepD, namely to increase the processivity of PcrA, allowing it to unwind plasmid lengths of DNA. A kinetic mechanism of RepD initiation is presented, showing rapid binding of the origin DNA. The rate of nicking varies with the structure of the DNA but can occur with a rate constant of >25 s(-1) at 30 °C. The equilibrium constant of the nicking reaction, which involves a transesterification to form a phosphotyrosine bond within the RepD active site, is close to unity.