In ovarian cancer, loss of BRCA gene expression in tumors is associated with improved response to chemotherapy and increased survival. A means to pharmacologically downregulate BRCA gene expression could improve the outcomes of patients with BRCA wild-type tumors. We report that vascular endothelial growth factor receptor 3 (VEGFR3) inhibition in ovarian cancer cells is associated with decreased levels of both BRCA1 and BRCA2. Inhibition of VEGFR3 in ovarian tumor cells was associated with growth arrest. CD133(+) ovarian cancer stemlike cells were preferentially susceptible to VEGFR3-mediated growth inhibition. VEGFR3 inhibition-mediated down-regulation of BRCA gene expression reversed chemotherapy resistance and restored chemosensitivity in resistant cell lines in which a BRCA2 mutation had reverted to wild type. Finally, we demonstrate that tumor-associated macrophages are a primary source of VEGF-C in the tumor microenvironment. Our studies suggest that VEGFR3 inhibition may be a pharmacologic means to downregulate BRCA genes and improve the outcomes of patients with BRCA wild-type tumors.

In this paper, we develop a new direct measure of state anti-smoking sentiment and merge it with micro-data on youth smoking in 1992 and 2000. The empirical results from the cross-sectional models show two consistent patterns: after controlling for differences in state anti-smoking sentiment, the price of cigarettes has a weak and statistically, insignificant influence on smoking participation, and state anti-smoking sentiment appears to have a potentially important influence on youth smoking participation. The cross-sectional results are corroborated by results from the discrete time hazard models of smoking initiation that include state-fixed effects. However, there is evidence of price-responsiveness in the conditional cigarette demand by youth and young adult smokers.

Neonates with this distinctive DWI pattern had a high positive rate of rotavirus infection, without evidence of other pathogens, and were characterized as term newborns with neurologic symptoms arising approximately the fifth day after birth. Although the specificity of this pattern is unclear, rotavirus testing should be considered for neonates presenting with this DWI pattern.