CUDC-101 is a novel, small-molecule, anticancer agent targeting histone deacetylase (HDAC), EGF receptor (EGFR), and HER2. It is currently in phase I clinical development in patients with solid tumors. Previously, we reported that CUDC-101 has potent antiproliferative and proapoptotic activity in cultured tumor cells and in vivo xenograft models. We now show that cancer cells that have acquired resistance to single-target EGFR inhibitors through upregulation of AXL or loss of E-cadherin remain sensitive to CUDC-101, which inhibits MET-and AXL-mediated signaling, restores E-cadherin expression, and reduces cell migration. CUDC-101 also efficiently inhibited the proliferation of MET-overexpressing non-small cell lung cancer and gastric cancer cell lines and inhibited the migration and invasion of invasive tumor cells. Taken together, these results suggest that coupling HDAC and HER2 inhibitory activities to an EGFR inhibitor may potentially be effective in overcoming drug resistance and preventing cancer cell migration. Mol Cancer Ther; 12(6); 925-36. Ó2013 AACR.

Use of the SQ by emergency physicians may predict 12-month mortality in older ED patients and may help emergency physicians identify older adults in need of palliative care interventions.

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Alcohol is an important compound used in food, agriculture, and medicine. In this study, we investigated the effect of alcohol on oocyte quality in mice by exposing animals for different duration times during an estrous cycle. Cumulus-oocyte complexes were collected from mice after pregnant mare serum gonadotropin- and human chorionic gonadotropin-induced superovulation. Ovulation number, E level in serum, and parthenogenetic embryo development in vitro were evaluated. Mitochondrial gene expression, mitochondrial membrane potential, and reactive oxygen species (ROS) levels in the cumulus were also assessed. The results showed that acute exposure to alcohol did not affect ovulation time (p > 0.05). Blasocyst formation rate in vitro was significantly improved after 1 and 2 days of alcohol exposure (p < 0.01). Mitochondrial membrane potential was significantly increased after 1-4 days of alcohol exposure (p < 0.05), but it decreased after 5 days (p < 0.05). ROS levels remained relatively low after 2, 3, and 4 days of exposure (p < 0.05), and they significantly increased after 6 days (p < 0.05). In addition, alcohol altered the expression of mitochondrial and nuclear genes in the cumulus. Taken together, our data suggest that acute exposure to alcohol affects oocyte quality by influencing the function and gene expression in the cumulus. These results underscore potential implications for the development of human reproductive therapeutics.