4-hydroxy estradiol-induced oxidant-mediated signaling is involved in the development of breast cancer

Breast cancer is a disease associated with excess exposures to estrogens. While the mode of cancer causation is unknown, others have shown that oxidative stress induced by prolonged exposure to estrogens mediates renal, liver, endometrial and mammary tumorigenesis though the mechanism(s) underling this process is unknown. In this study, we show that 4-hydroxyl 17β-estradiol (4-OHE2), a catechol metabolite of estrogen, induces mammary tumorigenesis in a redox dependent manner. We found that the mechanism of tumorigenesis involves redox activations of nuclear respiratory factor-1 (NRF1); a transcriptions factor associated with regulation of mitochondria biogenesis and oxidative phosphorylation (OXPHOS), as well as mediation of cell survival and growth of cells during periods of oxidative stress. Key findings from our study are as follows: (i) Prolonged treatments of normal mammary epithelial cells with 4-OHE2, increased the formation of intracellular reactive oxygen species (ROS). (ii) Estrogen-induced ROS activates redox sensitive transcription factors NRF1. (iii) 4-OHE2 through activation of serine-threonine kinase and histone acetyl transferase, phosphorylates and acetylate NRF1 respectively. (iv) Redox mediated epigenetic modifications of NRF1 facilitates mammary tumorigenesis and invasive phenotypes of breast cancer cells via modulations of genes involved in proliferation, growth and metastasis of exposed cells. (v) Animal engraftment of transformed clones formed invasive tumors. (vi) Treatment of cells or tumors with biological or chemical antioxidants, as well as silencing of NRF1 expressions, prevented 4-OHE2 induced mammary tumorigenesis and invasive phenotypes of MCF-10A cells. Based on these observations, we hypothesize that 4-OHE2 induced ROS epigenetically activate NRF1 through its phosphorylation and acylation. This, in turn, through NRF1-mediated transcriptional activation of the cell cycle genes, controls 4-OHE2 induced cell transformation and tumorigenesis.^

Kosher Airline Food: A Logistical Challenge

Providing meals to passengers on aircrafts requires a complex logistical system if it is to be done sucessfully. Variations to that system are required if special meals, such as kosher ones, are to be provided since it entails unique system challenges. The authors discuss service requirements, the challenges they pose to the inflight meal service logistical system, and some of the ways in which these challenges are met.

Managers' Perception of Alcohol Service Training Programs

In order to serve alcoholic beverages in a responsible manner, most managers turn to alcohol server training programs to provide effective standardized training for the alcohol server. Whether or not the programs are perceived by hospitality managers as effective has not been established. The author presents the results of a study of Oklahoma hospitality managers who perceive alcohol server training as becoming less effective.

Manager's Perceptions of Alcohol Server Staffing and Training Methods

Over-consumption of alcoholic beverages is a concern of managers of hotels and motels with a club/lounge, restaurant, and tavern. The authors surveyed members of two industry associations in Oklahoma to ascertain alcohol server training methods and managers' perception of the value of such programs.