Although the breast cancer susceptibility gene 1 (BRCA1) protein is predominantly nuclear, its localization can vary during the cell cycle in response to cellular insults. For example, in S-phase cells, BRCA1 forms subnuclear foci and localizes to the perinuclear region in response to DNA damage. The present study provides evidence that BRCA1 is transiently excluded from the nucleus during the early part of S phase in the absence of DNA damage. The percentage of MCF-7 human breast cancer cells predominantly expressing nonnuclear BRCA1 significantly correlates with the percentage of cells within early S phase. This redistribution of BRCA1 is partially sensitive to leptomycin B, indicating that CRM-1-mediated nuclear export is involved. Similar results were observed with MCF12A nonmalignant human mammary cells. The abilities of BAPTA-AM, an intracellular calcium chelator, to inhibit the change in BRCA1 localization, and of A23187, a calcium ionophore, and of thapsigargin to mimic nuclear exclusion of BRCA1, provide evidence for the involvement of calcium in this process. The calcium-mediated change in BRCA1 localization occurs in several cell lines, indicating that this effect is not cell line specific. BRCA2 localization is not affected by A23187. Furthermore, inhibition of calcium-calmodulin interaction and calciumcalmodulin dependent protein kinase II attenuates the calcium-mediated change in BRCA1 localization. These data suggest that BRCA1 nuclear export can be cell cycle-regulated by a calciumdependent mechanism.

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To test the efficacy of a community-based intervention, Empowering Communities for Life (EC4L), designed to increase colorectal cancer (CRC) screening through fecal occult blood test (FOBT) in rural underserved communities in a randomized controlled trial. Participants were randomized into 3 groups (2 interventions and 1 control). Interventions were delivered by community lay health workers or by academic health professionals. The main outcome of interest was return rate of FOBT screening kit within 60 days. Participants included 330 screening-eligible adults. The overall return rate of FOBT kits within 60 days was 32%. The professional group (Arm 2) had the highest proportion of returned FOBTs within 60 days at 42% (n = 46/110), a significantly higher return rate than the lay group (Arm 1) [28%(n = 29/103);P = 0.0422] or control group (Arm 3) [25%(n = 29/117);P = 0.0099]. Thus, one arm (Arm 2) of our intervention produced significantly higher CRC screening through FOBT. Community-based participation partnered with academic health professionals enhanced CRC screening among rural and poor-resourced communities.

Background: Consensus guidelines published in 2016 recommended a 2 mm free margin as the standard for negative margins in patients undergoing breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). The goal of the guideline recommendation was standardization of re-excision practices.Aims: To evaluate the impact of this consensus guideline on our institutional practices. Methods:We identified all patients at our institution with pure DCIS who were initially treated with BCS from September 2014 to August 2018 using a prospectivelymaintained institutional database. A retrospective chart review was performed to determine margin status and re-excision rates during the 2 years before and the 2 years after the guideline was published in order to determine the effect on our reexcision rates. Close margins were defined as <2 mm.Results: In the 2 years before the consensus guideline was published, 184 patients with DCIS underwent BCS. Twenty-six patients had positive margins and 24 underwent reexcision, including three who had completion mastectomy. Of the remaining 159 patients, 76 had ≥2 mm (negative) margins. The remaining 82 patients had close margins and 48 of these patients (58.5%) underwent re-excision, including one who had a completion mastectomy. Excluding the patients with positive margins, our re-excision rate was 30.4% prior to the guideline. In the 2 years after the consensus guideline was published, 192 patients with DCIS underwent initial BCS. Twenty-four patients had positive margins and 22 underwent re-excision, including three who had completion mastectomy. Of the remaining 168 patients, 95 patients had ≥2 mm (negative) margins. The remaining 73 patients had close margins and 45 of those patients (61.6%) underwent re-excision, including six who had completion mastectomy. Excluding the patients with positive margins, our re-excision rate was 26.8% after the guideline.Conclusions: Our institution's re-excision rate did not change significantly during the 2 years before and after the publication of the consensus guideline on adequate margins for patients undergoing BCT for DCIS. Our overall re-excision rate decreased slightly. However, of the patients who had close margins, a larger proportion underwent re-excision after the guideline was published. The guideline publication appears

The purpose of this study was to determine if race is a factor on overall survival when stage at diagnosis is compared. In this study, a total of 93 women with triple negative breast cancer (TNBC) were evaluated for survival outcomes after diagnosis between the year 2000 through 2010. Thirty-five patients (38%) were African American (AA), and 58 patients (62%) were Caucasian. Overall survival rates were estimated using the Kaplan-Meier method and compared between groups using the log-rank test. Student’s t-test was used to calculate differences in cancer recurrence and mortality rates by stage and race. Cox proportional hazards ratios were used to determine the association of patient and variables with clinical outcome. Of women diagnosed with stage 1 breast cancer, the overall survival rates for AAs was 100% compared to Caucasians at 94% (95% CI, 0.003 to 19; P = 0.5). For women with stage 2 breast cancer, overall survival for AA women was 85% and for Caucasian women was 86% (HR = 0.8; 95% CI, 0.3 to 2.6; P = 0.73). For advanced stages (stage 3 and 4), survival for AA women were 78% and 40% for Caucasian women (HR = 0.6; 95% CI 0.2 to 1.98; P = 0.43). Rates of recurrence and mortality were not significantly different between AA and Caucasian TNBC patients. After controlling for patient variables, race was not significantly associated with OS (HR = 1.24; 95% CI, 0.32 to 5.08; P = 0.74) when comparing AA to Caucasian patients. Our study suggests that race does not have an effect on overall survival in African American and Caucasian women diagnosed with TNBC in Arkansas.