Estrogen receptor-beta is a potential target for triple negative breast cancer treatment.

Triple Negative breast cancer (TNBC) is a subtype of breast cancer that lacks the expression of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2. TNBC accounts for 15-20% of all breast cancer cases but accounts for over 50% of mortality. We propose that Estrogen receptor-beta (ERβ) and IGF2 play a significant role in the pathogenesis of TNBCs, and could be important targets for future therapy. Tissue microarrays (TMAs) from over 250 TNBC patients' were analyzed for ERβ and IGF2 expression by immunohistochemistry. Expression was correlated with clinical outcomes. In addition, TNBC cell lines Caucasians (CA): MB-231/BT549 and African Americans (AAs): MB-468/HCC70/HCC1806 were used to investigate the effect of hormonal and growth factor regulation on cell proliferation. TMAs from AAs had higher expression of ERβ and IGF2 expression when compared to CA. ERβ and IGF2 were found to be upregulated in our TNBC cell lines when compared to other cell types. TNBC cells treated with ERβ agonist displayed significant increase in cell proliferation and migration when compared to controls. AA tissue samples from TNBC patients had higher expression of ERβ. African-American breast cancer TNBC tissue samples from TNBC patients have higher expression of ERβ. In addition, TNBC cell lines were also found to express high levels of ERβ. IGF2 increased transcription of ERβ in TNBC cells. Understanding the mechanisms of IGF2/ERβ axis in TNBC tumors could provide an opportunity to target this aggressive subtype of breast cancer

Receptors for Insulin-Like Growth Factor-2 and Androgens as Therapeutic Targets in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) occurs in 10-15% of all breast cancer patients, yet it accounts for about half of all breast cancer deaths. There is an urgent need to identify new antitumor targets to provide additional treatment options for patients afflicted with this aggressive disease. Preclinical evidence suggests a critical role for insulin-like growth factor-2 (IGF2) and androgen receptor (AR) in regulating TNBC progression. To advance this work, a panel of TNBC cell lines was investigated with all cell lines showing significant expression of IGF2. Treatment with IGF2 stimulated cell proliferation in vitro (p < 0.05). Importantly, combination treatments with IGF1R inhibitors BMS-754807 and NVP-AEW541 elicited significant inhibition of TNBC cell proliferation (p < 0.001). Based on Annexin-V binding assays, BMS-754807, NVP-AEW541 and enzalutamide induced TNBC cell death (p < 0.005). Additionally, combination of enzalutamide with BMS-754807 or NVP-AEW541 exerted significant reductions in TNBC proliferation even in cells with low AR expression (p < 0.001). Notably, NVP-AEW541 and BMS-754807 reduced AR levels in BT549 TNBC cells. These results provide evidence that IGF2 promotes TNBC cell viability and proliferation, while inhibition of IGF1R/IR and AR pathways contribute to blockade of TNBC proliferation and promotion of apoptosis in vitro

Shift Work in Nurses: Contribution of Phenotypes and Genotypes to Adaptation

Daily cycles of sleep/wake, hormones, and physiological processes are often misaligned with behavioral patterns during shift work, leading to an increased risk of developing cardiovascular/metabolic/gastrointestinal disorders, some types of cancer, and mental disorders including depression and anxiety. It is unclear how sleep timing, chronotype, and circadian clock gene variation contribute to adaptation to shift work.Newly defined sleep strategies, chronotype, and genotype for polymorphisms in circadian clock genes were assessed in 388 hospital day- and night-shift nurses.Night-shift nurses who used sleep deprivation as a means to switch to and from diurnal sleep on work days (∼25%) were the most poorly adapted to their work schedule. Chronotype also influenced efficacy of adaptation. In addition, polymorphisms in CLOCK, NPAS2, PER2, and PER3 were significantly associated with outcomes such as alcohol/caffeine consumption and sleepiness, as well as sleep phase, inertia and duration in both single- and multi-locus models. Many of these results were specific to shift type suggesting an interaction between genotype and environment (in this case, shift work).Sleep strategy, chronotype, and genotype contribute to the adaptation of the circadian system to an environment that switches frequently and/or irregularly between different schedules of the light-dark cycle and social/workplace time. This study of shift work nurses illustrates how an environmental "stress" to the temporal organization of physiology and metabolism can have behavioral and health-related consequences. Because nurses are a key component of health care, these findings could have important implications for health-care policy

Retention of faculty of color in academic nursing.

BACKGROUND: Racial and ethnic diversity among nursing faculty is low, preventing schools of nursing (SON) from reflecting the populations that they serve academically and clinically. Few studies address the experience and success of faculty of color (FOC) in nursing. PURPOSE: The purpose of this article is to summarize the current literature related to FOC retention and promotion. METHODS: We reviewed 25 articles from the nursing literature following PRISMA guidelines, using a critical race theory framework. DISCUSSION: We describe barriers and promoters to retention, benefits of retaining FOC, and proposed solutions to FOC attrition. We also highlight polices by several SON that netted increased retention and promotion of nursing FOC. CONCLUSION: FOC meet substantial challenges that influence their career pathway. SON can improve faculty retention through focused efforts on improving the institutional culture to promote an inclusive environment

Self-reported race and ethnicity of US biobank participants compared to the US Census

Precision medicine envisions a future of effective diagnosis, treatment, and prevention grounded in precise understandings of the genetic and environmental determinants of disease. Given that the original genome-wide association studies represented a predominately European White population, and that diversity in genomic studies must account for genetic variation both within and across racial categories, new research studies are at a heightened risk for inadequate representation. Currently biological samples are being made available for sequencing in biobanks across the USA, but the diversity of those samples is unknown. The aims of this study were to describe the types of recruitment and enrollment materials used by US biobanks and the diversity of the samples contained within their collection. Biobank websites and brochures were evaluated for reading level, health literacy, and factors known to encourage the recruitment of minorities, such as showing pictures of diverse populations. Biobank managers were surveyed by mail on the methods and materials used for enrollment, recruitment, consent, and the self-reported race/ethnicity of biobank participants. From 51 US biobanks (68% response rate), recruitment and enrollment materials were in English only, and most of the websites and brochures exceeded a fifth-grade reading level. When compared to the 2015 US Census, self-reported race/ethnicity of participants was not significantly different for Whites (61%) and blacks (13%). The percentages were significantly lower for Hispanics and Latinos (18 vs. 7%, p = 0.00) and Hawaiian/Pacific Islanders (0.2 vs. 0.01%; p = 0.01) and higher for Asians (13 vs. 5%, p = 0.01). Materials for recruitment predominantly in English may limit participation by underrepresented populations

Extranuclear signaling by sex steroid receptors and clinical implications in breast cancer.

Estrogen and progesterone play essential roles in the development and progression of breast cancer. Over 70% of breast cancers express estrogen receptors (ER) and progesterone receptors (PR), emphasizing the need for better understanding of ER and PR signaling. ER and PR are traditionally viewed as transcription factors that directly bind DNA to regulate gene networks. In addition to nuclear signaling, ER and PR mediate hormone-induced, rapid extranuclear signaling at the cell membrane or in the cytoplasm which triggers downstream signaling to regulate rapid or extended cellular responses. Specialized membrane and cytoplasmic proteins may also initiate hormone-induced extranuclear signaling. Rapid extranuclear signaling converges with its nuclear counterpart to amplify ER/PR transcription and specify gene regulatory networks. This review summarizes current understanding and updates on ER and PR extranuclear signaling. Further investigation of ER/PR extranuclear signaling may lead to development of novel targeted therapeutics for breast cancer management

Estrogen Receptor-β and the Insulin-Like Growth Factor Axis as Potential Therapeutic Targets for Triple-Negative Breast Cancer

Triple-negative breast cancers (TNBCs) lack estrogen receptor-α (ERα), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) amplification and account for almost half of all breast cancer deaths. This breast cancer subtype largely affects women who are premenopausal, African-American, or have BRCA1/2 mutations. Women with TNBC are plagued with higher rates of distant metastasis that significantly diminish their overall survival and quality of life. Due to their poor response to chemotherapy, patients with TNBC would significantly benefit from development of new targeted therapeutics. Research suggests that the insulin-like growth factor (IGF) family and estrogen receptor beta-1 (ERβ1), due to their roles in metabolism and cellular regulation, might be attractive targets to pursue for TNBC management. Here, we review the current state of the science addressing the roles of ERβ1 and the IGF family in TNBC. Further, the potential benefit of metformin treatment in patients with TNBC as well as areas of therapeutic potential in the IGF-ERβ1 pathway are highlighted