Search results for "Amide"
showing 10 items of 3119 documents
Increased hepatic fibrosis and JNK2-dependent liver injury in mice exhibiting hepatocyte-specific deletion of cFLIP.
2012
Chronic liver disease promotes hepatocellular injury involving apoptosis and triggers compensatory regeneration that leads to the activation of quiescent stellate cells in the liver. The deposition of extracellular matrix from activated myofibroblasts promotes hepatic fibrosis and the progression to cirrhosis with deleterious effects on liver physiology. The role of apoptosis signaling pathways in the development of fibrosis remains undefined. The aim of the current study was to determine the involvement of the caspase-8 homologue cellular FLICE-inhibitory protein (cFLIP) during the initiation and progression of fibrosis. Liver injury and fibrosis from carbon tetrachloride (CCl4) and thioa…
Fatty Liver and Fibrosis in Glycine N-Methyltransferase Knockout Mice Is Prevented by Nicotinamide
2010
Deletion of glycine N-methyltransferase (GNMT), the main gene involved in liver S-adenosylmethionine (SAM) catabolism, leads to the hepatic accumulation of this molecule and the development of fatty liver and fibrosis in mice. To demonstrate that the excess of hepatic SAM is the main agent contributing to liver disease in GNMT knockout (KO) mice, we treated 1.5-month-old GNMT-KO mice for 6 weeks with nicotinamide (NAM), a substrate of the enzyme NAM N-methyltransferase. NAM administration markedly reduced hepatic SAM content, prevented DNA hypermethylation, and normalized the expression of critical genes involved in fatty acid metabolism, oxidative stress, inflammation, cell proliferation, …
Elimination of quiescent/slow-proliferating cancer stem cells by Bcl-XL inhibition in non-small cell lung cancer
2014
Lung cancer is the most common cause of cancer-related mortality worldwide, urging the discovery of novel molecular targets and therapeutic strategies. Stem cells have been recently isolated from non-small cell lung cancer (NSCLC), thus allowing the investigation of molecular pathways specifically active in the tumorigenic population. We have found that Bcl-XL is constantly expressed by lung cancer stem cells (LCSCs) and has a prominent role in regulating LCSC survival. Whereas chemotherapeutic agents were scarcely effective against LCSC, the small molecule Bcl-2/Bcl-XL inhibitor ABT-737, but not the selective Bcl-2 inhibitor ABT-199, induced LCSC death at nanomolar concentrations. Differen…
RGD motifs on the surface of baculovirus enhance transduction of human lung carcinoma cells.
2006
Baculovirus vectors have been shown to enter a variety of mammalian cell lines and gene transfer with wild-type baculovirus (WT) has been demonstrated both in vitro and in vivo. Different protein motifs have been displayed on the viral surface to serve as ligands for cell-specific receptor molecules. We have generated recombinant baculovirus vectors displaying an RGD-motif, recognized by alphaV integrin, on the viral surface. The RGD motifs within the C-terminus of coxsackie virus A9 and human parechovirus 1 VP1 proteins were fused to the N-terminus of the major envelope glycoprotein, gp64, of Autographa californica multiple nucleopolyhedrovirus. The recombinant RGD-presenting viruses bound…
Acid Dnase Activities In Peripheral, Mononuclear Blood Cells: A Possible Parameter To Detect Proliferating Cell Populations
1992
After electrophoresis in DNA -containing polyacrylamide gels, two acid DNase activities can be detected in peripheral, mononuclear cells of the human blood. One of these acid DNase activities correlates with cell proliferation; its isoelectrical point is at pI 7.4. By means of this DNase activity, a quantity of less than 1% leukemic cells can be detected. The increased acid DNase activity can indicate the proliferation of malignant cell populations and possibly the proliferation of cell populations during immunological reactions
New amide and dioxopiperazine derivatives from leaves of Breynia nivosa
2017
The first chemical investigation of leaves of Breynia nivosa from Nigeria resulted in the isolation of two new amide derivatives breynivosamides A and B (1 and 2) and two new dioxopiperazine derivatives breynivosines A and B (4 and 5) together with seven known compounds (3, 6-11). The structures of the new compounds were elucidated by 1D, 2D NMR and HRESIMS data as well as by comparison with the literature. All isolated compounds were tested for the cytotoxic and antimicrobial activities. Only cristatin A (6) showed cytotoxicity against the L5178Y mouse lymphoma cell line with an IC50 value of 13.9μM while breynivosamide A (1) exhibited moderate antimicrobial activity against Mycobacterium …
Phenoloxidases in ascidian hemocytes: characterization of the pro-phenoloxidase activating system.
2003
The phenoloxidase (PO) activity of the hemocytes lysate supernatant from three ascidians species, assayed by means of 3-methyl-2-benzothiazolinone hydrazone hydrochloride, have been compared. PO-containing hemocytes were identified by a cytochemical reaction and the enzymatic activity measured by a spectrophotometric assay of lysate supernatant from hemocyte populations separated on a discontinuous Percoll density gradient. In Styela plicata, the enzyme appeared to be contained in morula cells only. In Ciona intestinalis, PO activity was shown in univacuolar refractile granulocyte and granular hemocyte. In Phallusia mammillata both compartment cell and granular hemocytes were positive. Enzy…
The novel dual PI3K/mTOR inhibitor GDC-0941 synergizes with the MEK inhibitor U0126 in non-small cell lung cancer cells.
2011
Lung cancer is a malignant disease with poor outcome, which has led to a search for new therapeutics. The PI3K/Akt/mTOR and Ras/raf/Erk pathways are key regulators of tumor growth and survival. In the present study, their roles were evaluated by MTT assay, flow cytometry and Western blotting in lung cancer cells. We found that a high efficacy of antitumor activity was shown with GDC-0941 treatment in two gefitinib-resistant non-small cell lung cancer (NSCLC) cell lines, A549 and H460. In addition, H460 cells with activating mutations of PIK3CA were relatively more sensitive to GDC-0941 than A549 cells with wild-type PIK3CA. Furthermore, GDC-0941 was highly efficacious in combination with U0…
Manganese overload affects p38 MAPK phosphorylation and metalloproteinase activity during sea urchin embryonic development.
2014
Abstract In the marine environment, manganese represents a potential emerging contaminant, resulting from an increased production of manganese-containing compounds. In earlier reports we found that the exposure of Paracentrotus lividus sea urchin embryos to manganese produced phenotypes with no skeleton. In addition, manganese interfered with calcium uptake, perturbed extracellular signal-regulated kinase (ERK) signaling, affected the expression of skeletogenic genes, and caused an increase of the hsc70 and hsc60 protein levels. Here, we extended our studies focusing on the temporal activation of the p38 mitogen-activated protein kinase (p38 MAPK) and the proteolytic activity of metalloprot…
Increased radioresistance via G12S K-Ras by compensatory upregulation of MAPK and PI3K pathways in epithelial cancer
2011
Background Irradiation-induced signaling via the 2 pathways, Raf-MEK-ERK and PI3K-Akt, is known to be closely associated with a limited response to radiotherapy. In the present study we analyzed the relevance of constitutively active K-Ras for postradiogenic pathway stimulation and the option of coordinated inhibition to overcome these rescue mechanisms. Methods We used 2 epithelial tumor cell lines as a model system, one of them harboring a G12S K-Ras mutation. Cells were irradiated and the effect of combined treatment with ionizing radiation and inhibitors on the expression of pERK and pAkt was determined by Western blotting. Additionally, clonogenic assays were performed to functionally …