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BRCA1, a multi-domain protein, is mutated in a large percentage of hereditary breast and ovarian cancers. BRCA1 is most often mutated in three domains or regions: the N-terminal RING domain, exons 11–13, and the BRCT domain. The BRCA1 RING domain is responsible for the E3 ubiquitin ligase activity of BRCA1 and mediates interactions between BRCA1 and other proteins. BRCA1 ubiquitinates several proteins with various functions. The BRCA1 BRCT domain binds to phosphoproteins with specific sequences recognized by both BRCA1 and ATM/ATR kinases. Structural studies of the RING and BRCT domains have revealed the molecular basis by which cancer causing mutations impact the functions of BRCA1. While no structural data is available for the amino acids encoded by exons 11–13, multiple binding sites and functional domains exist in this region. Many mutations in exons 11–13 have deleterious effects on the function of these domains. In this mini-review, we examine the structure-function relationships of the BRCA1 protein and the relevance to cancer progression.

Background:The non-nuclear BRCA1 tumor suppressor can stimulate cell death, but the mechanisms are unknown. Results: BRCA1 binds to the inositol 1,4,5-trisphophate receptor (IP 3 R) calcium channel at the endoplasmic reticulum to stimulate apoptotic calcium release. Conclusion: BRCA1 tumor suppressor activity includes direct stimulation of apoptotic cell death via increased IP 3 R activity. Significance: We identify a novel role for the tumor suppressor BRCA1.

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Study Objective The purpose of this analysis was to compare the trends in undergoing laparoscopic hysterectomy (versus abdominal or vaginal hysterectomy) based on patient age, race, median income and insurance type, from 2003 to 2010. Methods In this retrospective cohort study, we analyzed the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample databases from 2003–2010. All women who underwent a hysterectomy for either menorrhagia or leiomyoma were included, based on ICD-9 coding. The predicted probability of undergoing laparoscopic hysterectomy was determined for each year according to patient age, race, median income, and insurance type. The slopes of these values (i.e. the trend) was compared for each subgroup (i.e. black, white, Asian, etc.) in these categories. Main Results A total of 530, 154 cases were included in this study. Total number of hysterectomies decreased by 39% from 60,364 to 36,835 from 2003 to 2010. The percent of hysterectomies that were laparoscopic increased from 11% in 2003 to 29% in 2010. All groups analyzed experienced an increase in predicted probability of undergoing a laparoscopic hysterectomy. Of all women undergoing hysterectomy, the probability of undergoing a laparoscopic hysterectomy remained highest for women who were less than 35 years old, white, with the highest median income, and with private insurance from 2003–2010. The slope was significantly greater for (1) white females versus all other races analyzed (p<0.01), (2) females in the highest income quartile versus females in the lowest income quartile (p<0.01) and (3) females with private insurance versus females with Medicaid (p<0.01) or Medicare (p<0.01). Conclusions There remains a gap in distribution of laparoscopic hysterectomies with regards to age, race, median income and insurance type that does not seem to be closing, despite the increased availability of laparoscopic hysterectomies.

Background: Statins have broad-reaching effects beyond lowering plasma lipids, including antitumor properties. Results: Simvastatin inhibits proliferation and induces calcium-dependent apoptosis of human uterine leiomyoma cells. Conclusion:We report a novel calcium-mediated pathway associated with antitumor properties of simvastatin. Significance: Simvastatin may have antitumor properties significant for the treatment of human uterine leiomyomas.

Study Objective The objective of our study was to determine patient and hospital characteristics that were associated with undergoing laparoscopic hysterectomy compared with abdominal hysterectomy. Methods In this retrospective cohort study, we analyzed the 2010 Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database. All women who underwent laparoscopic or abdominal hysterectomy for either menorrhagia or leiomyoma were included, based on ICD9 coding. Linear model with binomial distribution and logit link function was used to determine patient and hospital characteristics associated with hysterectomy approach. Main Results A total of 32,436 patients were included in this study. Of these, 32% patients underwent laparoscopic hysterectomies and 67% underwent abdominal hysterectomies. With regards to patient characteristics, women younger than 35 years old were more likely to undergo laparoscopic hysterectomy when compared to each of the other age categories (p<0.001). White women were more likely to undergo laparoscopic hysterectomy than black women, Hispanic women or women classified as “other” races (p<0.001 for all comparisons). With regards to median income, patients from the lowest national quartile were less likely to undergo laparoscopic hysterectomy when compared to each of the other three national quartiles for income (p=0.01, p<0.001, p=0.001, respectively). Payment by private insurance was associated with laparoscopic hysterectomy when compared to payment by Medicare or payment by insurance category “other” (p<0.001 for both). With regards to hospital characteristics, hospitals in the Northeast were more likely to have laparoscopic hysterectomies than hospitals in the Midwest or South (p<0.001 for both comparisons); urban hospitals were more likely than rural hospitals (p<0.001); teaching hospitals were more likely than non-teaching hospitals (p<0.001); and government-owned hospitals were less likely than private, non-profit or private, investor owned (p<0.001 for both comparisons). Conclusions Despite the increased popularity of and training in laparoscopic hysterectomies, there remains an obvious disparity in its delivery with regards to patient and hospital characteristics. Further investigation is needed on the etiology of this disparity and interventions that may alleviate it.

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