Key Points
MAPK pathway activation and Bim loss may represent a fundamental mechanism of resistance to histone deacetylase inhibitors. Combination of romidepsin with an MEK inhibitor may lead to greater responses in cancers in which the MAPK pathway is active.
The seawater-adapting actions of GH, which are independent of growth, were studied in juvenile rainbow trout (Salmo gairdneri). Hormones examined were chum salmon (Oncorhynchus keta) GH (sGH) and prolactin (sPRL), and ovine GH (oGH). Plasma Na levels of freshwater-adapted fish peaked 24 h after transfer to 67% seawater and remained high for at least 48 h. Twenty-four hours after transfer, plasma Na levels were inversely correlated to body weight. In order to limit size and growth effects in all subsequent experiments, fish having a narrow range of body weights, fed a fixed diet, and injected with hormones over a short time-period were used. Plasma Na levels 24 h after transfer to 80% seawater were reduced significantly by sGH (0.25 and 2.5 micrograms/g) and oGH (2.5 micrograms/g) compared with saline injections, whereas sPRL (2.5 micrograms/g) had no significant effect. All the GH-treated fish had lower plasma Mg levels than controls; Ca levels were significantly reduced by the high dose of sGH. Salmon prolactin had no effect on concentrations of divalent ions. When the effects of a range of doses (0.01-1.25 micrograms/g) of sGH on plasma ion levels was tested, 0.25 micrograms/g was the most potent in reducing Na and Mg levels, while 1.25 microgram/g alone reduced plasma Ca concentrations significantly. These studies show that the seawater-adapting actions of GH in trout are specific to that hormone and are not consequent to an increase in size.
The intestinal role in osmoregulatory preadaptation of freshwater-adapted (FW) yearling coho salmon during smoltification was examined. Measurements of intestinal net fluid absorption (J,) using an in vitro sac preparation showed that J, of FW parr was significantly less than that of either FW or seawater-adapted (SW) smolts. From two to four weeks following the springtime thyroxin surge, J, increases in FW coho to a level comparable with that observed for SW srnolts. J, remained elevated in FW smolts throughout most of the summer and then decreased in the autumn. Two months after the thyroxin peak, intestinal wet weight per unit serosal surface area increases. Coho stunts resulting from premature transfer into sea water had significantly higher J, than that seen in SW smolts. The elevated J, of stunts is only partially explicable on the basis of differences in body weight between stunts and smolts.Our observations indicate that an increase in intestinal fluid absorption is a preadaptive change associated with smoltification occurring in concert with alterations in renal and branchial osmoregulatory mechanisms. The timing of the increase in J, suggests a phase relationship to the thyroxin surge. This temporal relationship may help to explain the efficacy of using changes in plasma thyroxin levels to predict hatchery-fish release dates that may optimize eventual seawater survival.
Cancer is one of the most common diseases afflicting humans. The use of biomarkers specific for tumor cells has facilitated their identification. However, technology has not kept pace with the field of molecular biomarkers, leaving their potential unrealized. Here, we demonstrate the efficacy of recognizing and capturing cancer cells using an antibody-based, on-chip, microfluidic device. A cancer cell capture biochip consisting of microchannels of size 2.0 cm long and 500 microm wide and deep, was etched onto Polydimethylsiloxane. Epithelial membrane antigen (EMA) and Epithelial growth factor receptor (EGFR) were coated on the inner surface of the microchannels. The overall chip measured 2.0 cm x 1.5 cm x 0.5 cm. Normal and tumor breast cells in a phosphate buffered saline (PBS) suspension were flowed through the biochip channels at a rate of 15 microL/min. Breast cancer cells were preferentially captured and identified while most of normal cells passed through. The capture rates for tumor and normal cells were found to be >30% and <5%, respectively. This preliminary cancer cell capture biochip design supports our initial effort of moving a BioMEMS device, from the bench top to the clinic.
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