Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Copper tetracarboranyltetraphenylporphyrin (CuTCPH) is a minimally toxic carborane-containing porphyrin that has safely delivered high concentrations of boron for experimental boron neutron capture therapy (BNCT). Copper octabromotetracarboranylphenylporphyrin (CuTCPBr), synthesized by bromination of CuTCPH, is one of several new minimally toxic analogues of CuTCPH being studied in our laboratory, which could possess comparable or better tumour-targeting properties with enhanced tumour cytotoxicity. Its biodistribution, biokinetics and toxicity in mice with subcutaneous EMT-6 (mammary) or SCCVII (squamous cell) carcinomas were compared with those of CuTCPH. The administration of approximately 200 mg kg(-1) of either porphyrin in six intraperitoneal injections over 2 days had no apparent effect, but administration of approximately 400 mg kg(-1) slightly lowered body weights, elevated alanine and aspartate transaminase activities in blood plasma, and depressed blood platelet counts for several days. Enzymes and platelets returned to normal within 5 days after those injections and body weights returned to normal within 2 weeks. High average concentrations of boron from either porphyrin were achieved in the two tumour models from a total dose of approximately 200 mg kg(-1). The high tumour boron concentration decreased slowly while concentrations in blood decreased rapidly. Boron concentrations in brain and skin were consistently lower than in tumour by a factor of 10 or more. Although either CuTCPH or CuTCPBr can be labelled with (64)Cu for imaging by positron emission tomography (PET), CuTCPBr can also be labelled by (76)Br, another PET-imageable nuclide.
...
PMID:Synthesis of copper octabromotetracarboranylphenylporphyrin for boron neutron capture therapy and its toxicity and biodistribution in tumour-bearing mice. 1523 4

The progressive development of a micro-fluidic manifold for the chemiluminescent detection of copper in water samples, based on the measurement of light emitted from the Cu(ii) catalysed oxidation of 1,10-phenanthroline by hydrogen peroxide, is reported. Micro-fluidic manifolds were designed and manufactured from polymethylmethacrylate (PMMA) using three micro-fabrication techniques, namely hot embossing, laser ablation and direct micro-milling. The final laser ablated design incorporated a reagent mixing channel of dimensions 7.3 cm in length and 250 x 250 microm in width and depth (triangular cross section), and a detection channel of 2.1 cm in length and 250 x 250 microm in width and depth (total approx. volume of between 16 to 22 microL). Optimised reagents conditions were found to be 0.07 mM 1,10-phenanthroline, containing 0.10 M cetyltrimethylammonium bromide and 0.075 M sodium hydroxide (reagent 1 delivered at 0.025 mL min(-1)) and 5% hydrogen peroxide (reagent 2 delivered at 0.025 mL min(-1)). The sample stream was mixed with reagent 1 in the mixing channel and subsequently mixed with reagent 2 at the start of the detection channel. The laser ablated manifold was found to give a linear response (R(2) = 0.998) over the concentration ranges 0-150 microg L(-1) and be reproducible (% RSD = 3.4 for five repeat injections of a 75 microg L(-1) std). Detection limits for Cu(ii) were found to be 20 microg L(-1). Selectivity was investigated using a copper selective mini-chelating column, which showed common cations found in drinking waters did not cause interference with the detection of Cu(ii). Finally the optimised system was successfully used for trace Cu(ii) determinations in a standard reference freshwater sample (SRM 1640).
...
PMID:Development of a micro-fluidic manifold for copper monitoring utilising chemiluminescence detection. 1526 9

Voltammetric methods are very suitable, versatile and rapid techniques for simultaneous determination of metals in complex matrices. The present work, determination of Cu(II), Sn(II), Sb(III), Tl(I), and Pb(II) by square-wave anodic-stripping voltammetry and Cr(VI) by square-wave adsorptive-stripping voltammetry, is an interesting example of the possibility of simultaneous determination of each single element in food and environmental samples, even in the presence of reciprocal interference. Dibasic ammonium citrate, pH 6.3 or 8.2, was employed as supporting electrolyte. The voltammetric measurements were carried out using a stationary hanging mercury drop electrode as working electrode and a platinum electrode and an Ag|AgCl|KCl(sat) electrode as auxiliary and reference electrodes, respectively. The analytical procedure was verified by analysis of standard reference materials--wholemeal BCR-CRM 189, wheat flour NIST-SRM 1567a, rice flour NIST-SRM 1568a, estuarine sediment BCR-CRM 277, river sediment BCR-CRM 320, and Montana soil with moderately elevated traces NIST-SRM 2711. Precision and accuracy, expressed as relative standard deviation and relative error, respectively, were generally below 6% whereas limits of detection for each element were below 0.069 microg g(-1). In the presence of reciprocal interference the standard addition method considerably improved the resolution of the voltammetric technique, even for very high element concentration ratios. After being set up on the standard reference materials the analytical procedure was transferred and applied to commercial samples of meal and soil samples taken from sites devoted to agricultural practice. A critical comparison with graphite furnace atomic-absorption spectroscopy is also discussed.
...
PMID:Overlapping voltammetric peaks--an analytical procedure for simultaneous determination of trace metals. Application to food and environmental matrices. 1567 34

Chocolate is a complex sample with a high content of organic compounds and its analysis generally involves digestion procedures that might include the risk of losses and/or contamination. The determination of copper in chocolate is important because copper compounds are extensively used as fungicides in the farming of cocoa. In this paper, a slurry-sampling flame atomic-absorption spectrometric method is proposed for determination of copper in powdered chocolate samples. Optimization was carried out using univariate methodology involving the variables nature and concentration of the acid solution for slurry preparation, sonication time, and sample mass. The recommended conditions include a sample mass of 0.2 g, 2.0 mol L(-1) hydrochloric acid solution, and a sonication time of 15 min. The calibration curve was prepared using aqueous copper standards in 2.0 mol L(-1) hydrochloric acid. This method allowed determination of copper in chocolate with a detection limit of 0.4 microg g(-1) and precision, expressed as relative standard deviation (RSD), of 2.5% (n = 10) for a copper content of approximately 30 microg g(-1), using a chocolate mass of 0.2 g. The accuracy was confirmed by analyzing the certified reference materials NIST SRM 1568a rice flour and NIES CRM 10-b rice flour. The proposed method was used for determination of copper in three powdered chocolate samples, the copper content of which varied between 26.6 and 31.5 microg g(-1). The results showed no significant differences with those obtained after complete digestion, using a t-test for comparison.
...
PMID:Determination of copper in powdered chocolate samples by slurry-sampling flame atomic-absorption spectrometry. 1589 68

A new sorbent was synthesized by anchoring 7-amino-4-azaheptyltrimetoxisilane, freshly prepared, to silica gel, producing 7-amino-4-azaheptyl anchored silica gel (AAHSG). This material was characterized by infrared spectroscopy (IR), elemental analysis (CHN), and nitrogen adsorption-desorption isotherms. Isotherms of the adsorption of Fe3+, Fe2+ and Cu2+ on AAHSG were recorded, which indicated that Fe3+ presents a higher affinity by the sorbent. Therefore, AAHSG was successfully employed as a sorbent in a simple flow system for the preconcentration of Fe3+ in natural water samples, such as, river water, lagoonwater, springwater, stream water, well water and two water reference materials (NIST-SRM 1640, NIST-SRM 1643d). The obtained preconcentration factor was 82.2, and the detection limit achieved was 5.9 ng ml(-1). The recovery of spiked water samples ranged from 95.0 - 103.1%.
...
PMID:7-amino-4-azaheptyl grafted onto a silica gel as a sorbent for the on-line preconcentration and determination of iron(III) in water samples. 1591 51

We have studied the effects of heavy metals (Hg2+, Cu2+, Cd2+) on growth hormone (GH) activation of tyrosine kinase and Ca2+ signaling in the trout (Oncorhynchus mykiss) hepatoma cell line RTH-149. Molecular cloning techniques using primer designed on Oncorhynchus spp. growth hormone receptor (GHR) genes allowed to isolate a highly homologous cDNA fragment from RTH-149 mRNA. Thereafter, cells were analysed by Western blotting or, alternatively, with Ca2+ imaging using fura-2/AM. Exposure of cells to ovine GH alone produced a stimulation of the JAK2/STAT5 pathway and intracellular free Ca2+ variations similar to what has been observed in mammalian models. Cell pre-exposure to Cu2+, Hg2+ or Cd2+ affected cell response to GH by enhancing (Cu2+) or inhibiting (Cd2+) the phosphorylation of JAK2 and STAT5. Heavy metals induced the activation of the MAP kinase p38, and pre-exposure to Hg2+ or Cu2+ followed by GH enhanced the effect of metal alone. Image analysis of fura2-loaded cells indicated that pre-treatment with Hg2+ prior to GH produced a considerable increase of the [Ca2+]i variation produced by either element, while using Cu2+ or Cd2+ the result was similar but much weaker. Data suggest that heavy metals interfere with GH as follows: Hg2+ is nearly ineffective on JAK/STAT and strongly synergistic on Ca2+ signaling; Cu2+ is activatory on JAK/STAT and slightly activatory on Ca2+; Cd2+ is strongly inhibitory on JAK/STAT and slightly activatory on Ca2+; heavy metals could partially activate STAT via p38 independently from GH interaction.
...
PMID:Heavy metal interference with growth hormone signalling in trout hepatoma cells RTH-149. 1595 44

The sorption conditions including pH of the aqueous solution, sample volume, etc., on Celtek clay of copper(II), cadmium(II), lead(II), chromium(III), nickel(II) and cobalt(II) ions from environmental samples has been studied. The effects of electrolytes as matrix on the preconcentration were also investigated with the recoveries >95%. The 3 sigma detection limits for copper, cadmium, lead, chromium, nickel and cobalt ions were found to be 0.25, 0.32, 0.73, 0.45, 0.50 and 0.41 microg/l, respectively. The relative standard deviation was <10% for the determination of analytes. The procedure was validated by analysis of a NRCC-SLRS 4 Riverine Water, SRM 1573a Tomato leaves and IAEA 336 Lichen standard reference materials. The developed method was successively utilized for the determination of Cu(II), Cd(II), Pb(II), Cr(III), Ni(II) and Co(II) in various samples including natural waters, wheat and human hair by flame atomic absorption spectrometry (FAAS) with satisfactorily results (recoveries>95% and R.S.D.'s<10%).
...
PMID:Celtek clay as sorbent for separation-preconcentration of metal ions from environmental samples. 1644 23

Three carboranyltetraphenylporphyrins containing 40 or 80 boron atoms were synthesized and evaluated for their biodistribution and toxicity in EMT-6 tumor-bearing mice. Copper (II) meso-5,10,15,20-tetrakis[3-methoxy-4-(o-carboranylmethoxy)phenyl]porphyrin, 6, and copper (II) meso-5,10,15,20-tetrakis[3-hydroxy-4-(o-carboranylmethoxy)phenyl]porphyrin, 8, are B40 congeners with different lipophilicities, each less than their B80 congener, copper (II) meso-5,10,15,20-tetrakis[m-(3,5-di-o-carboranylmethoxybenzyloxy)phenyl]porphyrin, 18. Two days after the last of a series of i.p. injections in BALB/c mice bearing EMT-6 mammary tumors, a dose of 185 mg/kg 6 (54 mg/kg B) delivered over 3.5 times the concentration of boron to tumor (169 microg/g B) than did 118 mg/kg 8 (36 mg/kg B), which delivered 35 microg/g B, or 87 mg/kg 18 (30 mg/kg B), which delivered 46 microg/g B. The tumor-to-blood and tumor-to-brain boron concentration ratios at that time for all three porphyrins exceeded 80:1. Two days after the last injection, there resulted moderate thrombocytopenia that essentially disappeared two days later from 6 and 18, and mild leukocytosis from 6, 8, and 18, all of which were clinically inconsequential. Thus, 6 may rank among the most clinically promising carboranyl porphyrins ever made to deliver 10B to tumors for boron neutron-capture therapy (BNCT) that has also been tested for its toxicity in vivo.
...
PMID:Total syntheses of three copper (II) tetracarboranylphenylporphyrins containing 40 or 80 boron atoms and their biological properties in EMT-6 tumor-bearing mice. 1665 Oct

The synthesis and characterization of Schiff base derivatives of 3-formylchromone 3-6 (FPA-120 to FPA-123), the minimal biologically active structural motif of soy isoflavone, genistein, and their copper(II) complexes 7-10 (FPA-124 to FPA-127) are reported here. These copper complexes possess distorted square-planar geometries capable of stabilizing Cu2+/Cu+ redox forms. The molecular modeling study revealed that the key interaction of the metal complexes was with amino acids in the pleckstrin homology (PH) and the kinase domain of the PKB (Akt) protein. Copper complex 7 significantly forms stronger charge interactions in the kinase domain than genistein, leading to better stabilization in the active pocket. In vitro evaluation of copper complexes against hormone-independent and metastatic breast (BT20), prostate (PC-3), and K-ras mutant (COLO 357) and K-ras wild-type (BxPC-3) pancreatic cancer cells revealed that 7 was the most potent compound which exhibited PKB (Akt protein) inhibitory activities and caused NF-kappaB inactivation in a well-established orthotopic pancreatic tumor model using COLO 357 cells. An inverse relationship was observed between IC50 values of the anti-proliferative activities and the Cu2+/Cu+ redox couple for these compounds, which may provide a rapid screen for evaluating the efficacy of active metallodrugs affecting redox-sensitive transcription factors such as NF-kappaB and its upstream target, the PKB (Akt) pathway, in multiple cancers.
...
PMID:Synthesis, molecular characterization, and biological activity of novel synthetic derivatives of chromen-4-one in human cancer cells. 1678 37

Periodic DFT and combined quantum mechanics/interatomic potential function (QM-pot) models were used to describe the interaction of CO with the Cu+ sites in FER. The CO stretching frequencies were calculated using omega(CO)(CCSD(T))/r(CO)(DFT) scaling method relating frequencies determined using a high-level quantum-chemical (coupled clusters) method for simple model carbonyls to CO bond lengths calculated using periodic DFT and QM-pot methods for the Cu+-zeolite system. Both periodic DFT and QM-pot models together with omega(CO)/r(CO) scaling describe the CO stretching dynamics with the "near spectroscopic accuracy", giving nu(CO) = 2156 cm(-1) in excellent agreement with experimental data. Calculations for various Cu+ sites in FER show that both types of Cu+ sites in FER (channel-wall sites and intersection sites) have the same CO stretching frequencies. Thus, the CO stretching frequencies are not site-specific in the CO/Cu+/FER system. The convergence of the results with respect to the model size was analyzed. When the same exchange-correlation functional is used the adsorption energies from periodic DFT and QM-pot are in good agreement (about 2 kcal/mol difference) but substantially larger than those of the experiment. The adsorption energy calculated with the B3LYP functional agrees with available experimental data. The overestimation of the adsorption energy in DFT calculations (periodic or QM-pot) is related to a red-shift of the CO stretching mode, both result from an underestimation of the HOMO(5sigma)-LUMO(2pi) gap of CO and the consequent overestimation of the Cu(+)(d)-CO(2pi*) back-donation. For the adsorption energy, this can be overcome by the use of hybrid B3LYP exchange-correlation functional. For the frequency calculations, the DFT problem can be overcome by the use of the omega(CO)(CCSD(T))/r(CO)(DFT) correlation.
...
PMID:Theoretical investigation of CO interaction with copper sites in zeolites: periodic DFT and hybrid quantum mechanical/interatomic potential function study. 1685 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---