Anti-proliferative activity of the quassinoid NBT-272 in childhood medulloblastoma cells

BACKGROUND: With current treatment strategies, nearly half of all medulloblastoma (MB) patients die from progressive tumors. Accordingly, the identification of novel therapeutic strategies remains a major goal. Deregulation of c-MYC is evident in numerous human cancers. In MB, over-expression of c-MYC has been shown to correlate with anaplasia and unfavorable prognosis. In neuroblastoma – an embryonal tumor with biological similarities to MB – the quassinoid NBT-272 has been demonstrated to inhibit cellular proliferation and to down-regulate c-MYC protein expression. METHODS: To study MB cell responses to NBT-272 and their dependence on the level of c-MYC expression, DAOY (wild-type, empty vector transfected or c-MYC transfected), D341 (c-MYC amplification) and D425 (c-MYC amplification) human MB cells were used. The cells were treated with different concentrations of NBT-272 and the impact on cell proliferation, apoptosis and c-MYC expression was analyzed. RESULTS: NBT-272 treatment resulted in a dose-dependent inhibition of cellular proliferation (IC50 in the range of 1.7 – 9.6 ng/ml) and in a dose-dependent increase in apoptotic cell death in all human MB cell lines tested. Treatment with NBT-272 resulted in up to 90% down-regulation of c-MYC protein, as demonstrated by Western blot analysis, and in a significant inhibition of c-MYC binding activity. Anti-proliferative effects were slightly more prominent in D341 and D425 human MB cells with c-MYC amplification and slightly more pronounced in c-MYC over-expressing DAOY cells compared to DAOY wild-type cells. Moreover, treatment of synchronized cells by NBT-272 induced a marked cell arrest at the G1/S boundary. CONCLUSION: In human MB cells, NBT-272 treatment inhibits cellular proliferation at nanomolar concentrations, blocks cell cycle progression, induces apoptosis, and down-regulates the expression of the oncogene c-MYC. Thus, NBT-272 may represent a novel drug candidate to inhibit proliferation of human MB cells in vivo

Chronic disease self-management education courses: utilization by low-income, middle-aged participants

Abstract Background Individuals living in lower-income areas face an increased prevalence of chronic disease and, oftentimes, greater barriers to optimal self-management. Disparities in disease management are seen across the lifespan, but are particularly notable among middle-aged adults. Although evidence-based Chronic Disease Self-management Education courses are available to enhance self-management among members of this at-risk population, little information is available to determine the extent to which these courses are reaching those at greatest risk. The purpose of this study is to compare the extent to which middle-aged adults from lower- and higher-income areas have engaged in CDSME courses, and to identify the sociodemographic characteristics of lower-income, middle aged participants. Methods The results of this study were produced through analysis of secondary data collected during the Communities Putting Prevention to Work: Chronic Disease Self-Management Program initiative. During this initiative, data was collected from 100,000 CDSME participants across 45 states within the United States, the District of Columbia, and Puerto Rico. Results Of the entire sample included in this analysis (19,365 participants), 55 people lived in the most impoverished counties. While these 55 participants represented just 0.3% of the total study sample, researchers found this group completed courses more frequently than participants from less impoverished counties once enrolled. Conclusion These results signal a need to enhance participation of middle-aged adults from lower-income areas in CDSME courses. The results also provide evidence that can be used to inform future program delivery choices, including decisions regarding recruitment materials, program leaders, and program delivery sites, to better engage this population