Targeting mTOR and Src restricts hepatocellular carcinoma growth in a novel murine liver cancer model.

Liver cancer is a poor prognosis cancer with limited treatment options. To develop a new therapeutic approach, we derived HCC cells from a known model of murine hepatocellular carcinoma (HCC). We treated adiponectin (APN) knock-out mice with the carcinogen diethylnitrosamine, and the resulting tumors were 7-fold larger than wild-type controls. Tumors were disassociated from both genotypes and their growth characteristics evaluated. A52 cells from APN KO mice had the most robust growth in vitro and in vivo, and presented with pathology similar to the parental tumor. All primary tumors and cell lines exhibited activity of the mammalian target of Rapamycin (mTOR) and Src pathways. Subsequent combinatorial treatment, with the mTOR inhibitor Rapamycin and the Src inhibitor Dasatinib reduced A52 HCC growth 29-fold in vivo. Through protein and histological analyzes we observed activation of these pathways in human HCC, suggesting that targeting both mTOR and Src may be a novel approach for the treatment of HCC.

Adiponectin confers protection from acute colitis and restricts a B cell immune response.

Adiponectin demonstrates beneficial effects in various metabolic diseases, including diabetes, and in bowel cancer. Recent data also suggest a protective role in colitis. However, the precise molecular mechanisms by which adiponectin and its receptors modulate colitis and the nature of the adaptive immune response in murine models are yet to be elucidated. Adiponectin knock-out mice were orally administered dextran sulfate sodium for 7 days and were compared with wild-type mice. The severity of disease was analyzed histopathologically and through cytokine profiling. HCT116 colonic epithelial cells were employed to analyze the in vitro effects of adiponectin and AdipoR1 interactions in colonic injury following dextran sulfate sodium treatment. Adiponectin knock-out mice receiving dextran sulfate sodium exhibited severe colitis, had greater inflammatory cell infiltration, and an increased presence of activated B cells compared with controls. This was accompanied by an exaggerated proinflammatory cytokine profile and increased STAT3 signaling. Adiponectin knock-out mouse colons had markedly reduced proliferation and increased epithelial apoptosis and cellular stress. In vitro, adiponectin reduced apoptotic, anti-proliferative, and stress signals and restored STAT3 signaling. Following the abrogation of AdipoR1 in vitro, these protective effects of adiponectin were abolished. In summary, adiponectin maintains intestinal homeostasis and protects against murine colitis through interactions with its receptor AdipoR1 and by modulating adaptive immunity.

Small Changes and Lasting Effects (SCALE) Trial: the formation of a weight loss behavioral intervention using EVOLVE.

BACKGROUND: Obesity is a major health problem that disproportionately affects Black and Hispanic adults. This paper presents the rationale and innovative design of a small change eating and physical activity intervention (SC) combined with a positive affect and self-affirmation (PA/SA) intervention versus the SC intervention alone for weight loss. METHODS: Using a mixed methods translational model (EVOLVE), we designed and tested a SC approach intervention in overweight and/ or obese African American and Hispanic adults. In Phase I, we explored participant's values and beliefs about the small change approach. In Phase II, we tested and refined the intervention and then, in Phase III we conducted a RCT. Participants were randomized to the SC approach with PA/SA intervention vs. a SC approach alone for 12 months. The primary outcome was clinically significant weight loss at 12 months. RESULTS: Over 4.5 years a total of 574 participants (67 in Phase I, 102 in Phase II and 405 in Phase III) were enrolled. Phase I findings were used to create a workbook based on real life experiences about weight loss and to refine the small change eating strategies. Phase II results shaped the recruitment and retention strategy for the RCT, as well as the final intervention. The RCT results are currently under analysis. CONCLUSION: The present study seeks to determine if a SC approach combined with a PA/SA intervention will result in greater weight loss at 12 months in Black and Hispanic adults compared to a SC approach alone.

A second chance: meanings of body weight, diet, and physical activity to women who have experienced cancer.

OBJECTIVE: To understand the meanings of diet, physical activity, and body weight in the context of women's cancer experiences. DESIGN: Grounded theory using 15 qualitative interviews and 3 focus groups. SETTING: Grassroots community cancer organizations in the northeastern United States. PARTICIPANTS: Thirty-six white women cancer survivors; 86% had experienced breast cancer. MAIN OUTCOME MEASURES: Participants' views of the meanings of body weight, diet, and physical activity in the context of the cancer. ANALYSIS: Procedures adapted from the constant comparative method of qualitative analysis using iterative open coding. RESULTS: Themes emerged along 3 intersecting dimensions: vulnerability and control, stress and living well, and uncertainty and confidence. Diet and body weight were seen as sources of increased vulnerability and distress. Uncertainty about diet heightened distress and lack of control. Physical activity was seen as a way to regain control and reduce distress. CONCLUSIONS AND IMPLICATIONS: Emergent themes of vulnerability-control, stress-living well, and uncertainty-confidence may aid in understanding and promoting health behaviors in the growing population of cancer survivors. Messages that resonated with participants included taking ownership over one's body, physical activity as stress reduction, healthy eating for overall health and quality of life, and a second chance to get it right.

Diet and body composition outcomes of an environmental and educational intervention among men in treatment for substance addiction.

OBJECTIVE: To determine the effect of an educational and environmental intervention on diet, body mass index, and waist circumference of men in substance addiction treatment. METHODS: One hundred three racially/ethnically diverse men in 6 urban substance addiction residential treatment facilities in Upstate New York participated in weekly nutrition and food classes and food environment changes to increase healthful food choices. The main outcomes of this controlled, quasi-experimental, pre-post evaluation study were diet, body mass index, and waist circumference. RESULTS: Forty-three (42%) participants with complete data reported significantly greater intakes of fruits and vegetables, lower intakes of calories from sweets and desserts, and a reduction in waist circumference (P ≤ .05) following the intervention, compared to the control period. CONCLUSIONS AND IMPLICATIONS: An educational and environmental intervention can be effective in promoting positive dietary behavior and reducing waist circumference among men in residential treatment. These results need to be confirmed in a larger, randomized trial.

Process evaluation of an environmental and educational nutrition intervention in residential drug-treatment facilities.

OBJECTIVE: To evaluate the implementation of a controlled, 6-week, environmental and educational intervention to improve dietary intake and body composition, and to study the association of implementation fidelity with diet and body composition outcomes. DESIGN: A process evaluation documented participation, dose of nutrition education delivered, participant satisfaction, fidelity and completeness of the food environment intervention implementation, and context through observations and interviews with staff and residents. Intervention sites were scored and categorized as high or low participation and implementation and compared on essential elements of the food environment and on diet and body composition outcomes. SETTING: Six urban residential drug-treatment facilities in Upstate New York. SUBJECTS: Fifty-five primarily black and white men in residential drug-treatment programmes. RESULTS: Participants were exposed to 94 % and 69 % of the educational and environmental elements, respectively. High implementation sites were significantly more likely to provide water and 100 % juice, offer fruit or vegetable salad, offer choices of fruits and vegetables, and limit fried foods. Mixed-model analysis of covariance revealed that participants in the high participation and implementation sites reported greater reductions in total energy, percentage of energy from sweets, daily servings of fats, oils and sweets, and BMI over the intervention period. Participants in low participation and implementation sites reported greater reductions in percentage of energy from fat. Differential implementation of environmental elements limited the intervention impact. CONCLUSIONS: These findings document the contribution of changes in eating environments to facilitate dietary behaviour change in community residential substance-abuse settings.

Multiple health behavior changes in a cancer prevention intervention for construction workers, 2001-2003.

INTRODUCTION: Few multiple behavior change interventions have addressed tobacco use in conjunction with fruit and vegetable consumption, particularly among high-risk blue-collar workers. Tools for Health, a cancer prevention intervention for construction laborers, was effective in achieving behavior change for smoking cessation and fruit and vegetable consumption separately. This study examines whether addressing smoking and fruit and vegetable consumption was successful in achieving positive change for both behaviors. We also explored possible explanations for the relationship between behavior changes in these 2 behavioral domains. METHODS: We retrospectively analyzed data from a randomized controlled trial testing a smoking cessation and fruit and vegetable consumption intervention for construction workers. We used survey data from 300 intervention participants to answer our primary research question: Did participants who reported being smokers at baseline successfully quit smoking and increase their fruit and vegetable consumption by the end of the intervention? We used qualitative data from 16 small group discussions to help interpret these results. RESULTS: Tools for Health participants achieved substantial levels of smoking cessation and increased their fruit and vegetable consumption, concurrently, during the course of the intervention. CONCLUSION: This study provides evidence that pairing smoking cessation with increasing fruit and vegetable consumption can be successful in a multiple behavior change intervention designed for high-risk blue-collar workers. Further, our findings provide potential directions for examining why this pairing might be complementary.

Perceptions of the environment for eating and exercise in a rural community.

OBJECTIVE: To understand how members of a rural community perceive the effect of the built, natural, and social environments on their food choice and physical activity behaviors. METHODS: A constructivist community environmental assessment was conducted including 17 individual qualitative interviews, 2 focus groups, and photo elicitation (n = 27) in a rural northeastern community where over 60% of the adult population is overweight or obese. RESULTS: Participants described social, natural, and physical environmental factors that influenced their food choice and physical activity behaviors. Overweight and obesity were variably presented as an individual and/or a collective problem. Participants described conflicting goals for food choice and physical activity in the community, and an interrelationship between the social and physical environments. CONCLUSIONS AND IMPLICATIONS: A community environmental assessment provides a view of the physical and social environments from the perspective of community residents that can serve as a foundation for locally tailored, community-based approaches to obesity prevention.

Work conditions and the food choice coping strategies of employed parents.

OBJECTIVE: How work conditions relate to parents' food choice coping strategies. DESIGN: Pilot telephone survey. SETTING: City in the northeastern United States (US). PARTICIPANTS: Black, white, and Hispanic employed mothers (25) and fathers (25) randomly recruited from low-/moderate-income zip codes; 78% of those reached and eligible participated. MAIN OUTCOME MEASURES: Sociodemographic characteristics; work conditions (hours, shift, job schedule, security, satisfaction, food access); food choice coping strategies (22 behavioral items for managing food in response to work and family demands (ie, food prepared at/away from home, missing meals, individualizing meals, speeding up, planning). ANALYSIS: Two-tailed chi-square and Fisher exact tests (P < or = .05, unless noted). RESULTS: Half or more of respondents often/sometimes used 12 of 22 food choice coping strategies. Long hours and nonstandard hours and schedules were positively associated among fathers with take-out meals, missed family meals, prepared entrees, and eating while working; and among mothers with restaurant meals, missed breakfast, and prepared entrees. Job security, satisfaction, and food access were also associated with gender-specific strategies. CONCLUSIONS AND IMPLICATIONS: Structural work conditions among parents such as job hours, schedule, satisfaction, and food access are associated with food choice coping strategies with importance for dietary quality. Findings have implications for worksite interventions but need examination in a larger sample.

Time scarcity and food choices: an overview.

Time scarcity, the feeling of not having enough time, has been implicated in changes in food consumption patterns such as a decrease in food preparation at home, an increase in the consumption of fast foods, a decrease in family meals, and an increase in the consumption of convenience or ready-prepared foods. These food choices are associated with less healthful diets and may contribute to obesity and chronic health problems such as cardiovascular disease, diabetes, and cancer. In spite of the potential importance for health, there has been little study of how time scarcity influences people's food choices. This paper presents an overview of time issues related to food choices and discuss applications of time research for nutrition and health researchers, policy makers, and practitioners interested in food choice.

It just really clicked: participant-perceived outcomes of community nutrition education programs.

OBJECTIVE: To understand participant-perceived outcomes of community nutrition education programs by low income adults. DESIGN: A grounded theory approach using qualitative interviews. SETTING: Rural and urban communities in New York State and Pennsylvania. PARTICIPANTS: 18 current and past participants in nutrition education programs for low income adults. PHENOMENA OF INTEREST: Participants' perceived outcomes of community nutrition education programs. ANALYSIS: Qualitative analysis derived from the constant comparative method. RESULTS: Participants described program experiences in three linked thematic areas: (1) a range of motives for program enrollment; (2) current roles, challenges and resources as program contexts; and (3) participant-perceived outcomes experienced throughout the program that were linked to their motives for enrolling. Short- and medium-term outcomes, especially social outcomes, were important to participants; positive experiences were linked to later behavior change by participants, even among those who did not initially report change. CONCLUSIONS AND IMPLICATIONS: Participant-perceived outcomes and program satisfaction were linked to enrollment motives and modified by whether participants' current worlds provided resources to put learning into practice. Participant inputs such as enrollment motives and resources should be included in planning models, assessed at multiple points, matched to expected program outcomes, and used to guide teaching.

Heparin-bonded Dacron or polytetrafluorethylene for femoropopliteal bypass: five-year results of a prospective randomized multicenter clinical trial.

OBJECTIVE: Dacron was largely abandoned for femoropopliteal bypass 30 years ago, because better patency rates were achieved with saphenous vein. Despite the range of potential prosthetics, polytetrafluoroethylne (PTFE) clearly predominates in current femoropopliteal practice. We compared heparin-bonded Dacron (HBD) with PTFE in a randomized multicenter clinical trial. METHOD: Over 28 months, 209 patients (179 above-knee disease, 30 below-knee disease) were randomized to receive HBD (n = 106) or PTFE (n = 103) grafts. Aspirin, 300 mg/d, was started before surgery, and was continued if tolerated. RESULTS: At follow-up for a minimum of 5 years (mean, 76 months; range, 60-89 months), 37 patients (17.7%) had died with patent grafts and 121 (58%) grafts were occluded. Primary patency rate, measured with Kaplan-Meier survival analysis, was 46% (95% confidence interval [CI], 35%-57%) at year 5 for HBD, compared with 35% for PTFE (CI, 25%-45%; P < .055). Long-term patency was achieved in only 4 of 78 interventions performed in 55 thrombosed grafts. Secondary patency rate for HBD was 47% (CI, 36%-58%), and for PTFE was 36% (CI, 26%-46%). Risk factors for arterial disease did not significantly influence prosthetic patency. Major limb amputation was necessary in 9 patients with HBD grafts and 20 patients with PTFE grafts (P < .025). Two amputations in the HBD group and 8 amputations in the PTFE group were in patients undergoing bypass surgery to treat claudication only. Limb salvage rate was 86% (CI, 77%-95%) and 74% (CI, 64%-84%), respectively. CONCLUSIONS: Significantly better patency rates were achieved with HBD than with PTFE at 3 years (P < .044), but the difference was no longer statistically significant at 5 years (P < .055). The incidence of major limb amputation, however, was significantly greater (P < .025) in the PTFE group compared with the HBD group at both 3 and 5 years of follow-up.