Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anoxia and apoptosis are both implicated in chronic tendon pathology, however the influence of anoxia on the viability of tendon cells is not known. The objectives of the current study were to (i) investigate the effect of oxygen withdrawal on the viability of porcine Achilles tendon cells (ATCs), and (ii) examine the ability of IGF-I, a factor with known regenerative properties in tendon, to prevent ATC death. Cultured ATCs were enclosed in an anaerobic chamber. The mechanism of cell death was examined by flow cytometry of ATCs double labeled with Annexin-V and propidium iodide (PI). Caspase activity was determined by a fluorometric assay, and nuclear morphology was examined by Hoechst staining. The cell death induced by anoxia was time-dependent, and was characterized by phosphatidylserine exposure on the outer membrane, caspase activation and DNA fragmentation. Death was inhibited by the addition of IGF-I in a dose-dependent manner. The ability of IGF-I to activate the pro-survival PKB pathway in ATCs was inhibited by LY294002, indicating the importance of PI3K in the response of ATCs to IGF-I. These data suggest that cell death induced by lack of oxygen is predominantly apoptotic and can be prevented by pro-survival IGF-I signaling. This mechanism may contribute to the beneficial effect of IGF-I on tendon.
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PMID:IGF-I activates PKB and prevents anoxic apoptosis in Achilles tendon cells. 1614 Feb 3

Employing methods of cell biology and proteome analysis tools, we examined effects of an inhibitor of histone deacetylases, sodium butyrate (SB), on the proliferation/differentiation characteristics of chronic myelogenous leukemia (CML)-derived cells K562. SB suppressed proliferation of K562 cells by inducing cell cycle arrest in G1 phase, which was followed by their transition to G0 phase (decrease of Ki-67 antigen-positive cells) and erythroid differentiation (increased glycophorin A expression and synthesis of hemoglobins). Neither terminal apoptosis (low counts of TUNEL-positive cells) nor necrosis (moderate counts of propidium iodide-positive cells) occurred. Importantly, SB attenuated protein expression of CML-related chimeric kinase BCR-ABL that is responsible for the deregulated proliferation of CML cells. The proteomic analysis (2-D electrophoresis combined with MALDI-TOF mass spectrometry and/or Western blotting) revealed several proteins that were differentially expressed or their mobility was altered due to butyrate treatment, namely, HSP90, HSP70, p23, cyclophilin A (CYPA), prefoldin2 (PFD2) and alpha-, gamma-, epsilon-human globin chains. Perturbation of HSP90 multichaperone complex of which BCR-ABL is the client protein is presumably a cause of BCR-ABL suppression. Changes in other proteins with chaperonic functions, CYPA and PFD2, may reflect SB antiproliferative and cytodifferentiation effects.
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PMID:The proteomic study of sodium butyrate antiproliferative/cytodifferentiation effects on K562 cells. 1697 90

In the present study we investigated the toxicity induced by exposing organotypic slice culture to beta-amyloid peptide 25-35 (25microM) for 1, 3, 6, 12, 24 and 48h. To elucidate a mechanism involved in its toxicity, we studied the PI3-K cell signaling pathway, particularly Akt/PKB, GSK-3beta, and PTEN proteins. Cell death was quantified by propidium iodide uptake and proteins were analyzed by immunoblotting. Our results showed a significant cell death after 48h of beta-amyloid 25-35 peptide exposition. The exposition of cultures to beta-amyloid peptide resulted in an increase in the phosphorylation state of Akt and GSK-3beta proteins after 6h, followed by a decrease of the phosphorylation state of these proteins after 12h of exposition. However, after 24h of peptide treatment, the phosphorylation of GSK-3beta presented a new increase while the phosphorylation of Akt remained down. The immunocontent of the PTEN protein, an indirect Akt phosphatase, increased after 24 and 48h of beta-amyloid exposition. These results suggest an involvement of Akt dephosphorylation/inactivation in the toxicity induced by the beta-amyloid 25-35 peptide in organotypic slice hippocampal culture, probably induced by increasing PTEN immunocontent. Taken together, our results provide more information about the molecular mechanisms involved on beta-amyloid peptide toxicity.
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PMID:Beta-amyloid peptide toxicity in organotypic hippocampal slice culture involves Akt/PKB, GSK-3beta, and PTEN. 1701 42

Our aim was to study the effects of cucurbitacin glucosides extracted from Citrullus colocynthis leaves on human breast cancer cell growth. Leaves were extracted, resulting in the identification of cucurbitacin B/E glucosides. The cucurbitacin glucoside combination (1:1) inhibited growth of ER(+) MCF-7 and ER(-) MDA-MB-231 human breast cancer cell lines. Cell-cycle analysis showed that treatment with isolated cucurbitacin glucoside combination resulted in accumulation of cells at the G(2)/M phase of the cell cycle. Treated cells showed rapid reduction in the level of the key protein complex necessary to the regulation of G(2) exit and initiation of mitosis, namely the p34(CDC2)/cyclin B1 complex. cucurbitacin glucoside treatment also caused changes in the overall cell morphology from an elongated form to a round-shaped cell, which indicates that cucurbitacin treatment caused impairment of actin filament organization. This profound morphological change might also influence intracellular signaling by molecules such as PKB, resulting in inhibition in the transmission of survival signals. Reduction in PKB phosphorylation and inhibition of survivin, an anti-apoptosis family member, was observed. The treatment caused elevation in p-STAT3 and in p21(WAF), proven to be a STAT3 positive target in absence of survival signals. Cucurbitacin glucoside treatment also induced apoptosis, as measured by Annexin V/propidium iodide staining and by changes in mitochondrial membrane potential (DeltaPsi) using a fluorescent dye, JC-1. We suggest that cucurbitacin glucosides exhibit pleiotropic effects on cells, causing both cell cycle arrest and apoptosis. These results suggest that cucurbitacin glucosides might have therapeutic value against breast cancer cells.
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PMID:Growth inhibitory activity of cucurbitacin glucosides isolated from Citrullus colocynthis on human breast cancer cells. 1704 94

The clinical value of aciclovir, oral or topical, in the episodic treatment of recurrent herpes virus infection is limited. Betadine (povidone-iodine) could provide a cheap, effective alternative for managing symptomatic recurrences. We describe a case where povidone-iodine was used successfully to treat a recurrence of genital herpes simplex and review the literature supporting povidone-iodine in the treatment of genital tract infections.
Int J STD AIDS 2006 Dec
PMID:Betadine for herpes simplex infection. 1721 66

Tumor angiogenesis is a process that requires migration, proliferation, and differentiation of endothelial cells. We hypothesized that decrease in pancreatic tumor growth due to inhibition of Src activity is associated with the inability of Src kinase to trigger a network of such signaling processes, which finally leads to endothelial cell death and angiogenesis-restricted tumor dormancy. The therapeutic efficacy of Src kinase inhibitor AZM475271 was tested in nude mice orthotopically xenografted with L3.6pl pancreatic carcinoma cells. No liver metastases and peritoneal carcinosis were detected and a significant effect on the average pancreatic tumor burden was observed following treatment with AZM475271, which in turn correlated with a decrease in cell proliferation and an increase in apoptotic endothelial cells. AZM475271 was shown to significantly inhibit migration of human umbilical vein endothelial cells in an in vitro Boyden Chamber cell migration assay. In a rat aortic ring assay we could demonstrate as well inhibition of endothelial cell migration and sprouting following therapy with Src kinase inhibitor at similar doses. The most conclusive anti-angiogenic activity of AZM475271 was demonstrated in vivo (mouse corneal micropocket assay) by showing a marked inhibition of basic fibroblast growth factor-induced neovascularization in response to systemic administration of AZM475271. Furthermore, we could show reduced proliferation of HUVECs determined with the TACS MTT Cell Viability Assay Kit. The blockade of Src kinase significantly reduced the level of VEGF in L3.6pl medium, the effect which was found also in the cell culture supernate from HUVECs. Inhibition of Src kinase by AZM475271 also showed prevention of survival signaling from VEGF and EGF receptors. Treatment with AZM475271 resulted in VEGF - dependent inhibition of tyrosine phosphorylation of FAK. HUVECs were also examined using propidium iodide staining for cell cycle analysis by FACS. Inhibition of Src kinase promoted HUVEC apoptosis in a dose-dependent manner. Taken together, our results suggest that the Src kinase inhibitor AZM475271, in addition to its effects on tumor cells, suppresses tumor growth and metastasis in vitro and in vivo potentially also by anti-angiogenic mechanisms.
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PMID:Effect of Src kinase inhibition on metastasis and tumor angiogenesis in human pancreatic cancer. 1748 19

In this study we compared and validated commercial immunoradiometric assays (IRMA) to determine thyroglobulin (Tg) levels in serum. From a set of 440 samples, 68 were selected to calculate the validation parameters and the clinical performance of the assays. The commercial kits evaluated were the Tg-CTK (DiaSorin), IRMAZenco Tg (ZenTech), and SELco-Tg (Medipan). We found that 21% of the collected samples were in the critical range of concentration. Detection limits were calculated as being below 3 microg/L. Intra- and inter-reproducibility were lower than 3.1% and 9.2%, respectively. Dilution and recovery studies provided quantitative determinations. Correlation regression coefficients from the results of the methods were obtained. The determined concentrations were compared with the clinical evidence of disease. Variation in the 125-iodine-labeled antibody concentration and control charts showed the robustness of the methods. Analysis time and the simplicity of the methods were also evaluated. Reliable Tg determination is important for monitoring patients with differentiated thyroid cancer (DTC), controlling other thyroid diseases, and assessing the quality of imaging techniques. A strategy for verification and comparison based on analytical parameters and clinical performance is proposed.
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PMID:Comparison of immunoradiometric assays for determination of thyroglobulin: a validation study. 1750 73

A CE-inductively coupled plasma mass spectrometric (CE-ICP-MS) method for iodine and bromine speciation analysis is described. Samples containing ionic iodine (I(-) and IO(3)(-)) and bromine (Br(-) and BrO(3)(-)) species are subjected to electrophoretic separation before injection into the microconcentric nebulizer (CEI-100). The separation has been achieved in a 50 cm length x 75 microm id fused-silica capillary. The electrophoretic buffer used is 10 mmol/L Tris (pH 8.0), while the applied voltage is set at -8 kV. Detection limits are 1 and 20-50 ng/mL for various I and Br compounds, respectively, based on peak height. The RSD of the peak areas for seven injections of 0.1 microg/mL I(-), IO(3)(-) and 1 microg/mL Br(-), BrO(3)(-) mixture is in the range of 3-5%. This method has been applied to determine various iodine and bromine species in NIST SRM 1573a Tomato Leaves reference material and a salt and seaweed samples obtained locally. A microwave-assisted extraction method is used for the extraction of these compounds. Over 87% of the total iodine and 83% of the total bromine are extracted using a 10% m/v tetramethylammonium hydroxide (TMAH) solution in a focused microwave field within a period of 10 min. The spike recoveries are in the range of 94-105% for all the determinations. The major species of iodine and bromine in tomato leaves, salt, and seaweed are Br(-), IO(3)(-), I(-), and Br(-), respectively.
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PMID:Determination of iodine and bromine compounds in foodstuffs by CE-inductively coupled plasma MS. 1794 Nov 14

Persistent T cell activation is a common finding in anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated systemic vasculitis (AAV) patients. Because imatinib, a selective inhibitor of the ABL, ARG, PDGFR and c-KIT tyrosine kinases, inhibits T cell activation, this study was conducted to evaluate the potential use of imatinib for the treatment AAV patients refractory to conventional therapy. In particular, we investigated the inhibition of T cell activation by this drug and its efficacy on activated T cells from anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated systemic vasculitides (AASV) patients. T cell stimulation has been induced by anti-CD3/anti-CD28 antibodies or by phorbol myristate acetate (PMA)/ionomycin. T cell proliferation was analysed by tritiumthymidine incorporation. Cell cycle progression was determined by propidium iodide staining using fluorescence activated cell sorter (FACS) analysis and by RNAse protection assay (RPA). Cytokine levels were assessed by enzyme-linked immunosorbent assay. T cell proliferation was inhibited significantly by imatinib, due most probably to cell cycle arrest in the G1-phase. This was paralleled by inhibition in the expression of cyclin-dependent kinases 1 and 2 mRNA. The expression of CD25 in naive and memory T cells was decreased significantly by imatinib in activated T cells. Similarly, conversion from naive to memory T cells after T cell activation was impaired by imatinib. Imatinib did not influence interleukin-2 and tumour necrosis factor-alpha production but increased interferon-gamma production. These observed effects of imatinib were similar in T cells from AASV patients and from healthy individuals. Imatinib might be an alternative therapeutical option for AASV patients refractory to conventional therapy.
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PMID:Imatinib mesylate, a new kid on the block for the treatment of anti-neutrophil cytoplasmic autoantibodies-associated vasculitis? 1819 Jun 1

High-precision gravimetric coulometry with a silver-perchloric acid coulometer is evaluated as an alternative to the conventional titrimetric method. The loss of weight (caused by electrolytic dissolution) of a highly pure silver anode in series with the cathode of a conventional constant-current titration system is measured and related to the number of equivalents of substance titrated. The precision of the method is determined by titrations of the Standard Reference Material 83C arsenious oxide (99.99% pure) with electrogenerated iodine, using biamperometric end-point detection. Depending on the size of the sample, an ultimate precision of 25 ppm is obtained. The assay for 0.5-g samples of the SRM material is 99.993(9) +/- 0.002(5)% purity.
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PMID:High-precision gravimetric coulometry using the silver-perchloric acid coulometer: Titration of arsenious oxide with electrogenerated iodine. 1896 4


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