75 research outputs found
Dual inhibition of histone deacetylases and phosphoinositide 3-kinase enhances therapeutic activity against B cell lymphoma
Phosphoinositide 3-kinase (PI3K) and Myc are known to cooperate in promoting the survival and growth of a variety of B-cell lymphomas. While currently there are no small molecule inhibitors of Myc protein, histone deacetylase (HDAC) inhibitors have been shown to reduce levels of Myc protein by suppressing its transcription. We assessed the efficacy of CUDC-907, a new rationally designed dual inhibitor of PI3K and HDACs, in a panel of lymphoma cell lines. CUDC-907 treatment resulted in a dose- and time-dependent growth inhibition and cell death of DLBCL cell lines, irrespective of the cell of origin. CUDC-907 treatment down-regulated the phosphorylation of PI3K downstream targets, including AKT, PRAS40, S6, and 4EBP1, increased histone 3 acetylation, and decreased Myc protein levels. SILAC-based quantitative mass spectrometry demonstrated that CUDC-907 treatment decreased the protein levels of several components of the B cell receptor (BCR) and Toll like receptor (TLR) pathways, including BTK, SYK, and MyD88 proteins. These cellular changes were associated with an inhibition of NF-kB activation. CUDC-907 demonstrated in vivo efficacy with no significant toxicity in a human DLBCL xenograft mouse model. Collectively, these data provide a mechanistic rationale for evaluating CUDC-907 for the treatment of patients with Myc and PI3K-dependent lymphomas
Observation of a Distribution of Internal Transverse Magnetic Fields in a Mn12-Based Single Molecule Magnet
A distribution of internal transverse magnetic fields has been observed in
single molecule magnet (SMM) Mn12-BrAc in the pure magnetic quantum tunneling
(MQT) regime. Magnetic relaxation experiments at 0.4 K are used to produce a
hole in the distribution of transverse fields whose angle and depth depend on
the orientation and amplitude of an applied transverse ``digging field.'' The
presence of such transverse magnetic fields can explain the main features of
resonant MQT in this material, including the tunneling rates, the form of the
relaxation and the absence of tunneling selection rules. We propose a model in
which the transverse fields originate from a distribution of tilts of the
molecular magnetic easy axes.Comment: 4 page
Freshwater fishes and water status in Mexico: A country-wide appraisal.
Mexico is the southernmost country in North America, and extends into Central America, south of the Isthmus
of Tehuantepec. The northern half of M´exico is located on the Temperate belt and is arid in character (Nearctic),
while the rest is within the Tropical belt (Neotropical). Climate varies from extremely temperate desert in the
north, to tropical humid in the south.M´exico has more than 500 freshwater fish species, about 271 of them country
endemics, and approximately 48 endemics from binational basins. There are still some 30–40 fish species not
yet described. There are 563 fish species colonizing coastal flood plain species. In addition to the numbers of
colonizing fishes, the burden of introduced exotics has also been growing. In 1904, only 4 species were recognized
as exotics; by 1997 the number had increased to 94, and by 2008 to 11
Evaluation of Oxyrase® enrichment method for isolation of Campylobacter jejuni from inoculated foods
Craniad migration of differing doses of new methylene blue injected into the epidural space after death of calves and juvenile pigs
Cranial migration of different volumes of new-methylene blue after caudal epidural injection in the horse
NONLINEAR DISUTILITY OF TRAVEL DELAY: IMPLICATIONS FOR TRAFFIC DIVERSION BENEFIT AND STRATEGY
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