The small molecule UCN-01 is a cyclin-dependent kinase (CDK) modulator shown to have antiproliferative effects against several in vitro and in vivo cancer models currently being tested in human clinical trials. Although UCN-01 may inhibit several serine-threonine kinases, the exact mechanism by which it promotes cell cycle arrest is still unclear. We have reported previously that UCN-01 promote...

OBJECTIVE UCN-01 (7-hydroxystaurosporine) is a small molecule cyclin-dependent kinase modulator currently under clinical development as an anticancer agent. In vitro studies have demonstrated that UCN-01 is strongly bound to the acute-phase reactant alpha (1)-acid glycoprotein (AAG). Here, we examined the role of protein binding as a determinant of the pharmacokinetic behavior of UCN-01 in pati...

UCN-01, a protein kinase C/cyclin-dependent kinase inhibitor, suppressed thymidylate synthase (TS) protein expression in a dose-dependent manner with near complete suppression at 1 microM after a 24-h exposure in human gastric cancer cell line SK-GT5. Other protein kinase C/cyclin-dependent kinase inhibitors, including flavopiridol and safingol, had a similar effect on TS protein expression, bu...

DNA-damaging agents arrest cell cycle progression at either G1 or G2. A variety of agents such as caffeine have been shown to abrogate the DNA damage-dependent G2 checkpoint and enhance cytotoxicity. Unfortunately, this strategy has not enhanced therapeutic activity because adequate concentrations of these modulators are not tolerated in vivo. Here, using Chinese hamster ovary cell lines, we sh...

In a recent investigation of solid D2 as a UCN source[1], it was surmised that the yield of UCN is correlated with the spin states of the deuterium molecules. Subsequently, detailed neutron scattering calculations and measurements of the UCN lifetime in mixtures of paraand ortho-deuterium quantitatively verified this conjecture.[2,3,4,5,6] The work we report here was motivated by our attempt to...

UCN-01, a protein kinase C/cydin-dependent kinase inhibitor, suppressed thymidylate synthase (TS) protein expression in a dose-dependent manner with near complete suppression at 1 LM after a 24-h exposure in human gastric cancer cell line SK-GT5. Other protein kinase C/cydindependent kinase inhibitors, including fiavopiridol and safingol, had a similar effect on TS protein expression, but to a ...

Urocortin 2 (Ucn 2) is a corticotrop releasing factor paralog peptide with many physiological functions and it has widespread distribution. There are some data on the cytoprotective effects of Ucn 2, but less is known about its neuro- and retinoprotective actions. We have previously shown that Ucn 2 is protective in ischemia-induced retinal degeneration. The aim of the present study was to exam...

Ultracold neutron (UCN) projection imaging is demonstrated using a boron-coated back-illuminated CCD camera and the Los Alamos UCN source. Each recorded through capture reactions with 10B. By direct detection at least one of byproducts α, 7Li γ (electron recoils) derived from reduction thermal noise scientific camera, signal-to-noise improvement on order 104 over indirect has been achieved. Sub...

We have determined for the first time the velocity distribution of neutrons from a solid H2 ultracold neutron (UCN) source. The spectrum rises sharply above 4.5m/s and has a maximum around 7m/s after transport in an 8m long guide. The number of neutrons in the UCN velocity range (< 7m/s) may be increased by a factor of two by placing the experiment 1m above the UCN source level. PACS. 29.25.Dz ...

Corticotropin-releasing factor (CRF) and urocortin (UCN) are potent regulators of Purkinje cell dendritic development including spines and synapses. Here, we demonstrate that CRF and UCN increase dendritic spine density in cerebellar Purkinje cells. Specific spine types in Purkinje cells are selectively affected: CRF promotes the mushroom type of spines, whereas at the same time UCN the thin ty...