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31.
Ryan Wilcox Bryan E Welm Jeffrey T Chang Evan Johnson Avrum Spira Stefanie S Jeffrey Andrea H Bild 《Molecular systems biology》2011,7(1)
Identifying the best drug for each cancer patient requires an efficient individualized strategy. We present MATCH (M erging genomic and pharmacologic A nalyses for T herapy CH oice), an approach using public genomic resources and drug testing of fresh tumor samples to link drugs to patients. Valproic acid (VPA) is highlighted as a proof‐of‐principle. In order to predict specific tumor types with high probability of drug sensitivity, we create drug response signatures using publically available gene expression data and assess sensitivity in a data set of >40 cancer types. Next, we evaluate drug sensitivity in matched tumor and normal tissue and exclude cancer types that are no more sensitive than normal tissue. From these analyses, breast tumors are predicted to be sensitive to VPA. A meta‐analysis across breast cancer data sets shows that aggressive subtypes are most likely to be sensitive to VPA, but all subtypes have sensitive tumors. MATCH predictions correlate significantly with growth inhibition in cancer cell lines and three‐dimensional cultures of fresh tumor samples. MATCH accurately predicts reduction in tumor growth rate following VPA treatment in patient tumor xenografts. MATCH uses genomic analysis with in vitro testing of patient tumors to select optimal drug regimens before clinical trial initiation. 相似文献
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Vertical ionization energies (VIEs) of medazepam, nordazepam and their molecular subunits have been calculated using the electron
propagator method in the P3/CEP-31G* approximation. Vertical electron affinities (VEAs) have been obtained with a ∆SCF procedure
at the DFT-B3LYP/6-31+G* level of theory. Excellent correlations have been achieved between IEcalc and IEexp, allowing reliable assignment of the ionization processes. Our proposed assignment differs in many instances from that previously
reported in the literature. The electronic structure of the frontier Dyson orbitals shows that the IE and EA values of the
benzodiazepines can be modulated by substitution at the benzene rings. Hardness values, evaluated as (IE − EA)/2, follow the
trend of the experimental singlet transition energies. Medazepam is a less hard (i.e., less stable) compound than nordazepam. 相似文献
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36.
An analysis of substrate binding interactions in the heme peroxidase enzymes: A structural perspective 总被引:1,自引:0,他引:1
Andrea Gumiero Clive L. Metcalfe Emma Lloyd Raven 《Archives of biochemistry and biophysics》2010,500(1):13-14484
The interactions of heme peroxidase enzymes with their substrates have been studied for many years, but only in the last decade or so has structural information begun to appear. This review looks at crystal structures for a number of heme peroxidases in complex with a number of (mainly organic) substrates. It examines the nature and location of the binding interaction, and explores functional similarities and differences across the family. 相似文献
37.
James A. Simmons Andrea Megela Simmons 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2011,197(5):585-594
Widely divergent vertebrates share a common central temporal mechanism for representing periodicities of acoustic waveform
events. In the auditory nerve, periodicities corresponding to frequencies or rates from about 10 Hz to over 1,000 Hz are extracted
from pure tones, from low-frequency complex sounds (e.g., 1st harmonic in bullfrog calls), from mid-frequency sounds with
low-frequency modulations (e.g., amplitude modulation rates in cat vocalizations), and from time intervals between high-frequency
transients (e.g., pulse-echo delay in bat sonar). Time locking of neuronal responses to periodicities from about 50 ms down
to 4 ms or less (about 20–300 Hz) is preserved in the auditory midbrain, where responses are dispersed across many neurons
with different onset latencies from 4–5 to 20–50 ms. Midbrain latency distributions are wide enough to encompass two or more
repetitions of successive acoustic events, so that responses to multiple, successive periods are ongoing simultaneously in
different midbrain neurons. These latencies have a previously unnoticed periodic temporal pattern that determines the specific
times for the dispersed on-responses. 相似文献
38.
Carlos H. Dumard Shana P. C. Barroso Guilherme A. P. de Oliveira Carlos A. M. Carvalho Andre M. O. Gomes José Nelson S. S. Couceiro Davis F. Ferreira Dirlei Nico Andrea C. Oliveira Jerson L. Silva Patrícia S. Santos 《PloS one》2013,8(11)
Whole inactivated vaccines (WIVs) possess greater immunogenicity than split or subunit vaccines, and recent studies have demonstrated that WIVs with preserved fusogenic activity are more protective than non-fusogenic WIVs. In this work, we describe the inactivation of human influenza virus X-31 by high hydrostatic pressure (HHP) and analyze the effects on the structure by spectroscopic measurements, light scattering, and electron microscopy. We also investigated the effects of HHP on the glycoprotein activity and fusogenic activity of the viral particles. The electron microscopy data showed pore formation on the viral envelope, but the general morphology was preserved, and small variations were seen in the particle structure. The activity of hemagglutinin (HA) during the process of binding and fusion was affected in a time-dependent manner, but neuraminidase (NA) activity was not affected. Infectious activity ceased after 3 hours of pressurization, and mice were protected from infection after being vaccinated. Our results revealed full viral inactivation with overall preservation of viral structure and maintenance of fusogenic activity, thereby conferring protection against infection. A strong response consisting of serum immunoglobulin IgG1, IgG2a, and serum and mucosal IgA was also detected after vaccination. Thus, our data strongly suggest that applying hydrostatic pressure may be an effective method for developing new vaccines against influenza A as well as other viruses. 相似文献
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Klaus Urbahns Michael H?rter Markus Albers Delf Schmidt Beatrix Stelte-Ludwig Ulf Brüggemeier Andrea Vaupel Christoph Gerdes 《Bioorganic & medicinal chemistry letters》2002,12(2):205-208
Vitronectin receptor (alpha(V)beta(3)) antagonism has been implicated as a mechanism for the treatment of restenosis following balloon angioplasty. In this work we present results from screening of a focused combinatorial library based on a biphenyl moiety. Our SAR studies led to the identification of compounds with subnanomolar activity, selectivity towards the related GPIIbIIIa receptor and functional activity on human smooth muscle cell migration. 相似文献