Green tea catechin intervention of reactive oxygen species-mediated ERK pathway activation and chronically induced breast cell carcinogenesis

Long-term exposure to low doses of environmental carcinogens contributes to sporadic human breast cancers. Epidemiologic and experimental studies indicate that green tea catechins (GTCs) may intervene with breast cancer development. We have been developing a chronically induced breast cell carcinogenesis model wherein we repeatedly expose non-cancerous, human breast epithelial MCF10A cells to bioachievable picomolar concentrations of environmental carcinogens, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P), to progressively induce cellular acquisition of cancer-associated properties, as measurable end points. The model is then used as a target to identify non-cytotoxic preventive agents effective in suppression of cellular carcinogenesis. Here, we demonstrate, for the first time, a two-step strategy that initially used end points that were transiently induced by short-term exposure to NNK and B[a]P as targets to detect GTCs capable of blocking the acquisition of cancer-associated properties and subsequently used end points constantly induced by long-term exposure to carcinogens as targets to verify GTCs capable of suppressing carcinogenesis. We detected that short-term exposure to NNK and B[a]P resulted in elevation of reactive oxygen species (ROS), leading to Raf-independent extracellular signal-regulated kinase (ERK) pathway activation and subsequent induction of cell proliferation and DNA damage. These GTCs, at non-cytotoxic levels, were able to suppress chronically induced cellular carcinogenesis by blocking carcinogen-induced ROS elevation, ERK activation, cell proliferation and DNA damage in each exposure cycle. Our model may help accelerate the identification of preventive agents to intervene in carcinogenesis induced by long-term exposure to environmental carcinogens, thereby safely and effectively reducing the health risk of sporadic breast cancer.     

Investigation of Predictors of Newborn Screening Refusal in a Large Birth Cohort in North Dakota,USA

Maternal and Child Health Journal - Objectives The objective of this study was to identify maternal and provider predictors of newborn screening (NBS) refusal in North Dakota between 2011 and 2014....     

Temporal changes in geographic disparities in access to emergency heart attack and stroke care: are we any better today?

The objective of this study was to investigate temporal changes in geographic access to emergency heart attack and stroke care. Network analysis was used to compute travel time to the nearest emergency room (ER), cardiac, and stroke centers in Middle Tennessee. Populations within 30, 60, and 90 min driving time to the nearest ER, cardiac and stroke centers were identified. There were improvements in timely access to cardiac and stroke centers over the study period (1999-2010). There were significant (p<0.0001) increases in the proportion of the population with access to cardiac centers within 30 min from 29.4% (1999) to 62.4% (2009) while that for stroke changed from 5.4% (2004) to 46.1% (2010). Most (96%) of the population had access to an ER within 30 min from 1999 to 2010. Access to care has improved in the last decade but more still needs to be done to address disparities in rural communities.