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61.
Cascone T Morelli MP Morgillo F Kim WY Rodolico G Pepe S Tortora G Berrino L Lee HY Heymach JV Ciardiello F 《Journal of cellular physiology》2008,216(3):698-707
The proteasome plays a pivotal role in the turnover of regulatory transduction proteins induced by activated cell membrane growth factor receptors. The epidermal growth factor receptor (EGFR) pathway is crucial in the development and progression of human epithelial cancers. Proteasome inhibition may sensitize human cancer cell lines to EGFR inhibitors. We investigated the growth inhibitory and pro-apoptotic effects of the proteasome inhibitor bortezomib in combination with anti-EGFR drugs, such as gefitinib, vandetanib, and cetuximab in EGFR-expressing human cancer cell lines. Bortezomib determined dose-dependent growth inhibition in a nine cancer cell line panel (IC(50) values, range 6-42 nM). A significant synergistic growth inhibitory effect was observed with the combination of bortezomib and each EGFR inhibitor in all cell lines (combination index, CI, range 0.10-0.55), which was accompanied by a significant induction in apoptosis by the combined treatment with bortezomib, cetuximab and vandetanib. In HCT-116 colon cancer and A549 lung adenocarcinoma cells, bortezomib plus EGFR inhibitor treatment induced a more effective inhibition of EGFR-activated down-stream signals, including a marked suppression in activated, phosphorylated Akt (P-Akt). In contrast, overexpression of a constitutively active P-Akt protected A549 cells by cell growth inhibition and apoptosis following treatment with bortezomib and EGFR inhibitors. The combined treatment with bortezomib and EGFR inhibitors has a synergistic growth inhibitory and pro-apoptotic activity in different human cancer cells which possess a functional EGFR-dependent autocrine growth pathway through to a more efficient and sustained inhibition of Akt. 相似文献
62.
A comprehensive understanding of the factors governing the efficiency of metallophthalocyanine-based photothermal sensitizers requires the knowledge of their excited-state dynamics. This can only be properly gained when the nature and energy of the excited states (often spectroscopically silent) lying between the photogenerated state and the ground state are known. Here the excited state deactivation mechanism of two very promising metallophthalocyanine-based photothermal sensitizers, NiPc(OBu)(8) and NiNc(OBu)(8), is reviewed. It is shown that time dependent density functional theory (TDDFT) methods are capable to provide reliable information on the nature and energies of the low-lying excited states along the relaxation pathways. TDDFT calculations and ultrafast experiments consistently show that benzoannulation of the Pc ring modifies the photodeactivation mechanism of the photogenerated S(1)(pi,pi*) state by inducing substantial changes in the relative energies of the excited states lying between the S(1)(pi,pi*) state and the ground state. 相似文献
63.
Rosini E Molla G Rossetti C Pilone MS Pollegioni L Sacchi S 《Journal of biotechnology》2008,135(4):377-384
Determination of the D-amino acid content in foods and in biological samples is a very important task. In order to achieve this goal we developed a biosensor employing the flavoenzyme D-amino acid oxidase from the yeast Rhodotorula gracilis. To produce a device in which the D-amino acid composition does not alter the results, both the wild-type and a number of mutants obtained by rational design and directed evolution approaches were used. An analysis of D-amino acid oxidase mutants activity on D-amino acid mixtures containing various ratios of neutral, acidic, and basic substrates identified the Amberzyme-immobilized T60A/Q144R/K152E and M213G mutants as the best choice: their response shows an only limited dependence on the solution composition when at least 20% of the D-amino acid is made up of D-alanine (standard error is approximately 5-9%). This is the first report, to our knowledge, demonstrating that the entire D-amino acid content can be determined by using a screen-printed electrode amperometric biosensor, with a detection limit of 0.25 mM and a mean response time of 10-15 min. The D-amino acid assay based on R. gracilis DAAO-biosensor is inexpensive, simple to perform, and rapid: the D-amino acid concentration of a variety of biological samples can be investigated using this assay. 相似文献
64.
Rossetti S Aulenta F Majone M Crocetti G Tandoi V 《Biotechnology and bioengineering》2008,100(2):240-249
An anaerobic microcosm set up with aquifer material from a 1,1,2,2-tetrachloroethane (TeCA) contaminated site and amended with butyrate showed a complete TeCA dechlorination to ethene. A structure analysis of the microbial community was performed by fluorescence in situ hybridization (FISH) with already available and on purpose designed probes from sequences retrieved through 16S rDNA clone library construction. FISH was chosen as identification tool to evaluate in situ whether the retrieved sequences belong to primary bacteria responsible for the biodegradative reactions. FISH probes identified up to 80% of total bacteria and revealed the absence or the marginal presence of known TeCA degraders and the abundance of two well-known H(2)-utilizing halorespiring bacteria, Sulfurospirillum (32.4 +/- 8.6% of total bacteria) and Dehalococcoides spp. (14.8 +/- 2.8), thereby providing a strong indication of their involvement in the dechlorination processes. These results were supported by the kinetic and thermodynamic analysis which provided indications that hydrogen was the actual electron donor for TeCA dechlorination. The specific probes, developed in this study, for known dechlorinators (i.e., Geobacter, Dehalobacter, and Sulfurospirillum species) represent a valuable tool for any future in situ bioremediation study as well as a quick and specific investigation tool for tracking their distribution in the field. 相似文献
65.
66.
Walter Fratta Giampaolo Mereu Paolo Chessa Elisabetta Paglietti GianLuigi Gessa 《Life sciences》1976,18(10):1157-1165
The effect of different benzodiazepines on food intake was studied in cats which had been trained to eat their daily food within 3 hours, under conditions in which emotional factors were not present. When benzodiazepines were administered (at a dose ranging from 0.1 to 3 mg/Kg) before feeding, they increased both the total amount of food eaten and also the rate at which food was injested. When they were administered at the end of the feeding period, these compounds made the animals resume eating voraciously. The order of decreasing potency of the benzodiazepines tested was: oxazepam, N-methyl-lorazepam, diazepam, chlordiazepoxide, pinazepam, medazepam. Oxazepam (3 mg/Kg) stimulated maximally the food intake, even when administered up to 12 hours before feeding. Finally, oxazepam antagonized the anorexigenic effect of d-amphetamine, but did not influence amphetamine-induced hyperactivity and stereotyped behavior. 相似文献
67.
68.
Cristina Pérez-Arnaiz Natalia Busto Javier Santolaya José M. Leal Giampaolo Barone Begoña García 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(3):522-531
Background
Stabilization of G-quadruplex helices by small ligands has attracted growing attention because they inhibit the activity of the enzyme telomerase, which is overexpressed in > 80% cancer cells. TMPyP4, one of the most studied G-quadruplex ligands, is used as a model to show that the ligands can exhibit different binding features with different conformations of a human telomeric specific sequence.Methods
UV–Vis, FRET melting Assay, Isothermal Titration Calorimetry, Time-resolved Fluorescence lifetime, T-Jump and Molecular Dynamics.Results
TMPyP4 yields two different complexes with two Tel22 telomeric conformations in the presence of Na+ or K+. T-Jump kinetic experiments show that the rates of formation and dissociation of these complexes in the ms time scale differ by one order of magnitude. MD simulations reveal that, in K+ buffer, “hybrid 1” conformation yields kinetic constants on interaction with TMPyP4 one order lower than “hybrid 2”. The binding involves π–π stacking with external loop bases.Conclusions
For the first time we show that for a particular buffer TMPyP4 interacts in a kinetically different way with the two Tel22 conformations even if the complexes formed are thermodynamically indistinguishable.General significance
G-quadruplexes, endowed with technological applications and potential impact on regulation mechanisms, define a new research field. The possibility of building different conformations from same sequence is a complex issue that confers G-quadruplexes very interesting features. The obtaining of reliable kinetic data constitutes an efficient tool to determine reaction mechanisms between conformations and small molecules. 相似文献69.
Detection and typing of amyloid deposits in tissues are two crucial steps in the management of systemic amyloidoses. The presence of amyloid deposits is routinely evaluated through Congo red staining, whereas proteomics is now a mainstay in the identification of the deposited proteins. In article number 1700236, Winter et al. [Proteomics 2017, 17, Issue 22] describe a novel method based on MALDI–MS imaging coupled to ion mobility separation and peptide filtering, to detect the presence of amyloid in histology samples and to identify its composition, while preserving the spatial distribution of proteins in tissues. 相似文献
70.
The characterization and description of representatives of 'G' bacteria from activated sludge plants 总被引:2,自引:0,他引:2
L. L. Blackall S. Rossetti C. Christensson M. Cunningham P. Hartman P. Hugenholtz & V. Tandoi 《Letters in applied microbiology》1997,25(1):63-69
The name Tetracoccus cechii is proposed for two strains of the tetrad arranged cocci, previously known as 'G' bacteria, which were isolated from laboratory scale activated sludge plants in the Czech Republic and in Italy. They were morphologically, phenotypically and phylogenetically characterized and found to comprise a novel lineage in the alpha-3 group of the proteobacterial phylum in the domain Bacteria . The strains are Gram-negative and produce intracellular inclusions of poly-β-hydroxybutyrate. Although commonly seen in activated sludge mixed liquor as cocci 1–2 μm in diameter, arranged in tetrads, in pure culture they can also grow in amorphous aggregations and the cells are generally more variable in their size and shape with coccobacilli as well as cocci being present. They are not able to grow phototrophically, nor can they reduce nitrate beyond nitrite nor grow anaerobically. The closest phylogenetic neighbours of T. cechii are Rhodobacter sphaeroides and R. capsulatus which are 93% similar by 16S rDNA comparison. Tetracoccus cechii is oxidase- and catalase-positive, non-motile and has an optimal growth temperature between 25° and 35°C. The 16S rRNA of T. cechii has a 21 nucleotide deletion in the V9 region ( Escherichia coli positions 1258–1278) and this feature is a unique molecular synapomorphy in the alpha-3 group. 相似文献