Targeting AKT/mTOR Signaling Pathways During Murine Skin Tumor Promotion and the Impact of Dietary Energy Balance Manipulation

The prevalence of obesity has continued to rise over the last several decades in the United States lending to overall increases in risk for chronic diseases including many types of cancer. In contrast, reduction in energy consumption via calorie restriction (CR) has been shown to be a potent inhibitor of carcinogenesis across a broad range of species and tumor types. Previous data has demonstrated differential signaling through Akt and mTOR via the IGF-1R and other growth factor receptors across the diet-induced obesity (DIO)/CR spectrum. Furthermore, mTORC1 is known to be regulated directly via nutrient availability, supporting its role in the link between epithelial carcinogenesis and diet-induced obesity. In an effort to better understand the importance of mTORC1 in the context of both positive and negative energy balance during epithelial carcinogenesis, we have employed the use of specific pharmacological inhibitors, rapamycin (mTORC1 inhibitor) and metformin (AMPK activator) to target mTORC1 or various components of this pathway during skin tumor promotion. Two-stage skin carcinogenesis studies demonstrated that mTORC1 inhibition via rapamycin, metformin or combination treatments greatly inhibited skin tumor development in normal, overweight and obese mice. Furthermore, mechanisms by which these chemopreventive agents may be exerting their anti-tumor effects were explored. In addition, the effect of these compounds on the epidermal proliferative response was analyzed and drastic decreases in epidermal hyperproliferation and hyperplasia were found. Rapamycin also inhibited dermal inflammatory cell infiltration in a dose-dependent manner. Both compounds also blocked or attenuated TPA-induced signaling through epidermal mTORC1 as well as several downstream targets. In addition, inhibition of this pathway by metformin appeared to be, at least in part, dependent on AMPK activation in the skin. Overall, the data indicate that pharmacological strategies targeting this pathway offset the tumor-enhancing effects of DIO and may serve as possible CR mimetics. They suggest that mTORC1 contributes significantly to the process of skin tumor promotion, specifically during dietary energy balance effects. Exploiting the mechanistic information underlying dietary energy balance responsive pathways will help translate decades of research into effective strategies for prevention of epithelial carcinogenesis.

Effectiveness of a nutrition education program for women in a residential program after incarceration

Background: The number of incarcerated women has increased dramatically over the past two decades. During their stay in prison, the medical and nutritional needs of these women are frequently ignored. Overweight or obesity related to poor dietary habits and low-income status are important risk factors for health inequities. Women in this population are at risk for dietary-related chronic diseases such as hypertension, diabetes, and cardiovascular diseases. This is an indication that there is a need for nutrition education in this population. ^ Purpose: The purpose of this study was to provide an evidence-based nutrition education program at a facility for previously incarcerated women in Downtown Houston, Texas (Brigid's Hope). This nutrition education program focused on promoting better health and prevention of chronic diseases by increasing fruit and vegetable (FV) intake and healthy eating on a limited budget. Constructs such as knowledge, skills, self-efficacy, and perceived barriers were evaluated as well as acceptability, feasibility, and sustainability of the program. ^ Methods: The Hope for Health Nutrition Education Program occurred in four weekly sessions at Brigid's Hope. The evaluation design was a one-group quasi-experimental design with pre- and post-test measures. Identical pre- and post-tests were administered before and after the intervention. A total of 11 residents and 2 staff members participated in the study. Results: After four nutrition education sessions, post-tests revealed an overall increase in knowledge, skills, and self-efficacy scores, and decrease in perceived barrier scores towards FV consumption. Changes in skills, self-efficacy, and perceived barriers scores were found to be statistically significant. Participant satisfaction surveys revealed overall high satisfaction of the program and that continuing the program in the future would be possible with support from staff member and mentors. ^ Conclusions: Results from this study show that a nutrition education program can have positive effects towards knowledge, skills, self-efficacy, and perceived barriers towards FV consumption for previously incarcerated women. The high satisfaction for this program shows that a health promotion program with focus on diet and nutrition can play an important role in helping this unique population of women re-enter society.^

Perceptions of institutional support of community -based participatory research within prevention research centers

The Institute of Medicine (IOM) report on the future of health care states that the focus on health needs to shift to the management and prevention of chronic illnesses and that academic health centers (AHCs) should play an active role in this process through community partnerships (IOM, 2002). Grant funding from the National Institutes of Health and the creation of the Centers for Disease Control and Prevention (CDC) Prevention Research Centers (PRC) across the county represent a transition toward more proactively seeking out community partnerships to better design and disseminate health promotion programs (Green, 2001). ^ The focus of the PRCs is to conduct rigorous, community-based, prevention research, to seek outcomes applicable to public health programs and policies. The PRCs work is to create and foster partnerships among public health and community organizations, to address health promotion and disease prevention issues (CDC, 2003). ^ The W.K. Kellogg Foundation defines CBPR as "a collaborative approach to research that equitably involves all partners in the research process and recognizes the unique strengths that each brings. CBPR begins with a research topic of importance to the community with the aim of combining knowledge and action for social change to improve community health." ^ In 1995, CDC asked the IOM to review the PRC program to examine the extent to which the program is providing the public health community with strategies to address public health problems in disease prevention and health promotion (IOM, 1997). No comprehensive evaluation n of the individual PRCs had ever been done (IOM, 1997). ^ The CDC was interested in understanding how it could better support the PRC program through improved management and oversight to influence the program's success. The CDC only represents one of the entities that influence the success of a PRC. Another key entity to consider is the support of and influence of the Schools of Public Health in which the PRCs reside. Using evaluation criteria similar to those that were developed by the IOM, this study examined how aspects of structural capacity of the Schools of Public Health in which the PRCs reside are perceived to influence PRC community-based research activities. ^