Peroxiredoxin (Prdx) proteins are thiol-specific antioxidants that protect cells from oxidative stress in many normal and disease states. There are six Prdx proteins expressed in mammals, each with a characteristic tissue expression, subcellular distribution and substrate specificity. Recent studies have revealed elevated Prdx levels in many cancers, suggesting a protective role for these proteins in cancer cell survival. The present study is the first to investigate the function of all six Prdx proteins in the MCF-7 breast cancer cell line. We show that these cells have both higher resistance to doxorubicin-induced toxicity and significantly elevated Prdx levels, compared to the non-cancer MCF-10A cells. Using transient siRNA transfections, we show that Prdx3 suppression leads to decreased MCF-7 cell survival in the absence of doxorubicin. We further demonstrate that individual suppression of four of six of the Prdx proteins leads to increased doxorubicin-induced toxicity by apoptosis. Finally, we show that clonal selection of a doxorubicin-resistant MCF-7 subline by 2-week culture in 0.1 µM doxorubicin resulted in a marked elevation in the expression of several Prdx proteins. Together, these data reveal a protective function for peroxiredoxins in MCF-7 cell survival, and suggest that Prdx overexpression in breast cancer may play a role in doxorubicin-resistance in these, and possibly other, breast cancer cells. This study is the first to investigate the function of the entire Prdx family in a breast cancer cell line.

Background: Preoperative dental screening before cardiac valve surgery is widely accepted but its required scope remains unclear. This study evaluates two preoperative dental screening (PDS) approaches, a focused approach (FocA) and a comprehensive approach (CompA), to compare postsurgical 90-day mortality. Methods: Retrospective cohort analysis was performed on all patients who underwent valve surgery at Brigham and Women's Hospital with FocA and Massachusetts General Hospital with CompA of PDS approach from January 2009 to December 2016. Patients with intravenous drug abuse and systemic infections were excluded. Univariate, multivariable, and subgroup analysis was performed. Results: A total of 1835 patients were included in the study. With FocA 96% of patients (1097/1143) received dental clearance in a single encounter with 3.3% receiving radiographs and undergoing dental extractions. With CompA 35.5% of patients (245/692) received dental clearance in a single encounter, 94.2% received radiographs, and 21.8% underwent dental extractions. There was no significant difference in 90-day mortality when comparing both PDS approach (10% vs 8.4%, P = .257). This remained unchanged in a multivariable model after adjusting for risk factors (odds ratio:1.32 [95%CI:0.91-1.93] [P = .14]). Reoperation due to infection was less in FocA (0.5%) vs CompA (2.6) (P < .001) and postoperative septicemia was increased in the FocA (1.7%) cohort when compared to the CompA (0.7%) (P < .001) patients. Conclusions: There was no difference in post valve surgery 90-day mortality between patients who underwent a FocA vs CompA of PDS.

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