Roles for estrogen and progesterone in breast cancer prevention

Prevention has long been the holy grail of breast cancer research. The significant reduction in breast cancer risk afforded by a full-term pregnancy early in life suggests the great potential of preventive strategies. In contrast to the risks associated with prolonged exposures, exogenous estrogen and progesterone for short durations can mimic the protective effects of pregnancy in carcinogen-induced mammary tumor models. Rajkumar and coworkers have now demonstrated that these hormones protect mice from mammary tumors initiated by a spectrum of oncogenic alterations that are common in breast cancers. Although differences between rodent models and humans remain, the results reveal that exogenous estrogen and progesterone potently inhibit tumorigenesis through multiple pathways and establish a foundation for strategies to prevent breast cancer

Creating Devices for Personal Health Monitoring

As part of the mini-symposium entitled Creating Devices for Personalized Health Monitoring, Dr. Jerry introduces the symposium with a presentation about the Center for Personalized Health Monitoring (CPHM). The CPHM is an interdisciplinary research, training, and technology development center in wearable sensor systems for personalized health and biometric monitoring. CPHM’s mission is to conduct basic and translational research with world-leading impact across the entire technical roadmap for advanced personalized health monitoring for acute care and tele-medicine settings

A Case of Mistaken Identity: Biomarkers for High Risk Premalignant Breast Lesions

Discusses projects to develop biomarkers to predict atypical hyperplasias that may progress to invasive breast cancer. This presentation is part of the retreat mini-symposium entitled: Biomarker Discovery and Targeted Therapeutics in Cancer

Evaluation of Electronic Truck Monitoring

Automatic vehicle identification (AVI) and weigh-in-motion (WIM) equipment were installed at the northbound weigh/enforcement station on 1-65 in Simpson County, Kentucky. The objectives were to determine the reliability and accuracy of the equipment and to determine the benefits/costs for the trucking industry and enforcement agencies. The test site for evaluation of the equipment became operational in July 1991 and the evaluation continued through June 1993. AVI equipment was provided by Amtech Corporation and WIM equipment by International Road Dynamics. Participating motor carriers were United Parcel Service and Averitt Express, with a total of 114 trucks equipped with transponders. The system operated the first year with the AVI and WIM systems serving only the function of verifying the passage of an equipped truck. During the second phase, the AVI/WIM system was moved to a position in advance of the station where equipped trucks could be identified and given a preclearance signal. Overall, it was determined that the electronic equipment could be used to collect data more accurately than through a manual process. However, it was also found that AVI and WlM equipment were not without problems, particularly when interfacing the two types of equipment. Benefits gained were Increased levels of understanding of the reliability of AVI and WIM equipment Improved relationships between motor carriers and enforcement personnel were seen as a benefit. A preliminary evaluation of systemwide application of AVI does not indicate it would be cost-effective unless greater benefits were gained by motor carriers

Regulation of cancer stem cells by p53

The hypothesis that cancer stem cells are responsible for the chemoresistant and metastatic phenotypes of many breast cancers has gained support using cell-sorting strategies to enrich the tumor-initiating population of cells. The mechanisms regulating the cancer stem cell pool, however, are less clear. Two recent publications suggest that loss of p53 permits expansion of presumptive cancer stem cells in mouse mammary tumors and in human breast cell lines. These results add restriction of cancer stem cells as a new tumor suppressor activity attributed to p53

Ethical Issues and Decision Making in Collaborative Financial Therapy

The purpose of this article is to introduce potential ethical challenges that may arise when a financial and mental health professional collaborate to provide financial therapy and recommendations on how to effectively address these concerns. The development of ethical and professional practices requires extensive dialogue from practitioners in the emerging field of financial therapy; however, it is important to first develop an awareness and sensitivity to the ethical and professional issues across disciplines. This article examines the differences and similarities between the codes of ethics of different financial and mental health disciplines, and addresses six core ethical and professional issues: dual relationships, confidentiality, collaborating with other professionals, fee management, use of technology, and attending to federal and state regulatory laws. In working through the complexity of different disciplines’ regulatory environments, a discussion of how to address these ethical questions in order to progress the financial therapy field is presented

Estrogen and progesterone induce persistent increases in p53-dependent apoptosis and suppress mammary tumors in BALB/c-Trp53+/- mice

INTRODUCTION Treatment with estrogen and progesterone (E+P) mimics the protective effect of parity on mammary tumors in rodents and depends upon the activity of p53. The following experiments tested whether exogenous E+P primes p53 to be more responsive to DNA damage and whether these pathways confer resistance to mammary tumors in a mouse model of Li-Fraumeni syndrome. METHODS Mice that differ in p53 status (Trp53+/+, Trp53+/-, Trp53-/-) were treated with E+P for 14 days and then were tested for p53-dependent responses to ionizing radiation. Responses were also examined in parous and age-matched virgins. The effects of hormonal exposures on tumor incidence were examined in BALB/c-Trp53+/- mammary tissues. RESULTS Nuclear accumulation of p53 and apoptotic responses were increased similarly in the mammary epithelium from E+P-treated and parous mice compared with placebo and age-matched virgins. This effect was sustained for at least 7 weeks after E+P treatment and did not depend on the continued presence of ovarian hormones. Hormone stimulation also enhanced apoptotic responses to ionizing radiation in BALB/c-Trp53+/- mice but these responses were intermediate compared with Trp53+/+ and Trp-/- tissues, indicating haploinsufficiency. The appearance of spontaneous mammary tumors was delayed by parity in BALB/c-Trp53+/- mice. The majority of tumors lacked estrogen receptor (ER), but ER+ tumors were observed in both nulliparous and parous mice. However, apoptotic responses to ionizing radiation and tumor incidence did not differ among outgrowths of epithelial transplants from E+P-treated donors and nulliparous donors. CONCLUSION Therefore, E+P and parity confer a sustained increase in p53-mediated apoptosis within the mammary epithelium and suppress mammary tumorigenesis, but this effect was not retained in epithelial outgrowths.This work was supported by grants from the US Army Medical Research and Materiel Command (W81XWH0410385 to KAD and DAMD17-01-1-0315 to ACB) and the National Institutes of Health (RO1-CA095164 to DJJ)

Problem Identification for Highway Safety Plan

To comply with Section 402, Title 23 of the United States Code, each state is required to prepare an annual highway safety program. Kentucky\u27s program, which includes identification, programming, budgeting, and evaluation of highway safety projects, is intended to have a positive impact on the reduction of traffic accidents. The first step in the program, problem identification, requires systematic, statistical analyses of accident records. In-depth analyses of accident data were performed, and 29 problem areas were investigated. Accident rates were found for counties and cities in the following categories: total accidents; fatal accidents; accidents by driver age and sex; and speed-, alcohol-, and drug-related accidents. In addition, rates were reported for accidents involving pedestrians, bicycles, motorcycles, school buses, commercial buses, combination trucks, single-unit trucks, railroad trains, and emergency vehicles. This is the second report on problem identification prepared for the Office of Highway Safety Programs. Last year\u27s problem identification analysis was included in its entirety in Kentucky\u27s Annual Highway Safety Plan for Fiscal Year 1980

Safety Improvement Program for Toll Roads

This report presents proposed safety improvements for Kentucky\u27s toll roads. The primary methods of identifying needed improvements were an accident analysis and a field inventory. The accident analysis identified specific high-accident spots and sections. Also, accident rates were calculated for each toll road, and the types of accidents which had occurred in the 3-year period were summarized. A separate 10-year analysis of fatal accidents was made. The field inventory was used to identify roadway features which are now substandard and in need of upgrading. Also, high-accident spots and sections were investigated in the field. The benefits and costs for each improvement were estimated and used as input into a dynamic programming model used as a means of priority ranking the improvements. A total of 42 improvement alternatives were included in the analysis at an estimated cost of $58.5 million. Those alternatives with benefit-cost ratios greater than 1.0 totaled only$8.7 million

Problem Identification for Highway Safety Plan (FY 1983)

An annual highway safety program is proposed each year for the State of Kentucky in order to comply with Section 402, Title 23 of the United States code. This program includes the identification, programming, budgeting, and evaluation of safety projects. This report is the fourth in a series of annual reports which have been included as the problem identification portion of Kentucky\u27s Annual Highway Safety Plan. The approach used in this study involved identifying problem areas related to the 18 highway safety program standards with added emphasis placed on selected areas. This resulted in the analysis of 19 problem identification areas. Recommendations were made for programs which could serve as countermeasures for the highway safety problems identified and for studies to develop and evaluate such programs