Pubertal high fat diet: effects on mammary cancer development

INTRODUCTION: Epidemiological studies linking dietary fat intake and obesity to breast cancer risk have produced inconsistent results. This may be due to the difficulty of dissociating fat intake from obesity, and/or the lack of defined periods of exposure in these studies. The pubertal mammary gland is highly sensitive to cancer-causing agents. We assessed how high fat diet (HFD) affects inflammation, proliferative, and developmental events in the pubertal gland, since dysregulation of these can promote mammary tumorigenesis. To test the effect of HFD initiated during puberty on tumorigenesis, we utilized BALB/c mice, for which HFD neither induces obesity nor metabolic syndrome, allowing dissociation of HFD effects from other conditions associated with HFD. METHODS: Pubertal BALB/c mice were fed a low fat diet (12% kcal fat) or a HFD (60% kcal fat), and subjected to carcinogen 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumorigenesis. RESULTS: HFD elevated mammary gland expression of inflammatory and growth factor genes at 3 and 4 weeks of diet. Receptor activator of nuclear factor kappa-B ligand (RANKL), robustly induced at 4 weeks, has direct mitogenic activity in mammary epithelial cells and, as a potent inducer of NF-κB activity, may induce inflammatory genes. Three weeks of HFD induced a transient influx of eosinophils into the mammary gland, consistent with elevated inflammatory factors. At 10 weeks, prior to the appearance of palpable tumors, there were increased numbers of abnormal mammary epithelial lesions, enhanced cellular proliferation, increased growth factors, chemokines associated with immune-suppressive regulatory T cells, increased vascularization, and elevated M2 macrophages. HFD dramatically reduced tumor latency. Early developing tumors were more proliferative and were associated with increased levels of tumor-related growth factors, including increased plasma levels of HGF in tumor-bearing animals. Early HFD tumors also had increased vascularization, and more intra-tumor and stromal M2 macrophages. CONCLUSIONS: Taken together in this non-obesogenic context, HFD promotion of inflammatory processes, as well as local and systemically increased growth factor expression, are likely responsible for the enhanced tumorigenesis. It is noteworthy that although DMBA mutagenesis is virtually random in its targeting of genes in tumorigenesis, the short latency tumors arising in animals on HFD showed a unique gene expression profile, highlighting the potent overarching influence of HFD

Preparedness Perceptions, Sociodemographic Characteristics, and Level of Household Preparedness for Public Health Emergencies: Behavioral Risk Factor Surveillance System, 2006-2010

Our objective was to inform state and community interventions focused on increasing household preparedness by examining the association between self-reported possession of household disaster preparedness items (ie, a 3-day supply of food and water, a written evacuation plan, and a working radio and flashlight) and perceptions of household preparedness on a 3-point scale from “well prepared” to “not at all prepared.” Data were analyzed from 14 states participating in a large state-based telephone survey: the 2006-2010 Behavioral Risk Factor Surveillance System (BRFSS) ( n  = 104,654). Only 25.3% of the population felt they were well prepared, and only 12.3% had all 5 of the recommended items. Fewer than half the households surveyed had 4 or more of the recommended preparedness items (34.1%). Respondents were more likely to report their households were well prepared as the number of preparedness items possessed by their household increased. Risk factors for having no preparedness items were: younger age, being female, lower levels of education, and requesting the survey to be conducted in Spanish. To increase household disaster preparedness, more community-based preparedness education campaigns targeting vulnerable populations, such as those with limited English abilities and lower reading levels, are needed. The authors examined the association between self-reported possession of household disaster preparedness items (ie, a 3-day supply of food and water, a written evacuation plan, and a working radio and flashlight) and perceptions of household preparedness on a 3-point scale from “well prepared” to “not at all prepared.” Data were analyzed from 14 states participating in the 2006-2010 Behavioral Risk Factor Surveillance System (BRFSS) ( n  = 104,654). Only 25.3% of the population felt they were well prepared, and only 12.3% had all 5 of the recommended items. Risk factors for having no preparedness items were: younger age, being female, lower levels of education, and requesting the survey to be conducted in Spanish. To increase household disaster preparedness, more community-based preparedness education campaigns targeting vulnerable populations, such as those with limited English abilities and lower reading levels, are needed

Extreme rejuvenation and softening in a bulk metallic glass

Deforming metallic glasses can rejuvenate them to higher energy states, but only in the shear bands where deformation is usually concentrated. Here, the authors use a notched setup to suppress shear banding and promote significant bulk softening of a zirconium-based metallic glass

A role for PP1/NIPP1 in steering migration of human cancer cells

Peer reviewedPublisher PD