Search results for "Growth Inhibitor"

Loss of PHD3 allows tumours to overcome hypoxic growth inhibition and sustain proliferation through EGFR

2014

Solid tumours are exposed to microenvironmental factors such as hypoxia that normally inhibit cell growth. However, tumour cells are capable of counteracting these signals through mechanisms that are largely unknown. Here we show that the prolyl hydroxylase PHD3 restrains tumour growth in response to microenvironmental cues through the control of EGFR. PHD3 silencing in human gliomas or genetic deletion in a murine high-grade astrocytoma model markedly promotes tumour growth and the ability of tumours to continue growing under unfavourable conditions. The growth-suppressive function of PHD3 is independent of the established PHD3 targets HIF and NF-κB and its hydroxylase activity. Instead, l…

The Cell Cycle-Specific Growth-Inhibitory Factor Produced by Actinobacillus actinomycetemcomitans Is a Cytolethal Distending Toxin

1998

ABSTRACT Actinobacillus actinomycetemcomitans has been shown to produce a soluble cytotoxic factor(s) distinct from leukotoxin. We have identified in A. actinomycetemcomitans Y4 a cluster of genes encoding a cytolethal distending toxin (CDT). This new member of the CDT family is similar to the CDT produced by Haemophilus ducreyi . The CDT from A. actinomycetemcomitans was produced in Escherichia coli and was able to induce cell distension, growth arrest in G 2 /M phase, nucleus swelling, and chromatin fragmentation in HeLa cells. The three proteins, CDTA, -B and -C, encoded by the cdt locus were all required for toxin activity. Antiserum raised against recombinant CDTC completely inhibited …

The designer cytokine hyper-IL-6 mediates growth inhibition and GM-CSF-dependent rejection of B16 melanoma cells.

2000

The low immunogenic B16 melanoma cell line was transfected with a mammalian expression vector containing the complementary DNA for a sIL-6R/IL-6 fusion protein, termed Hyper-IL-6 (H-IL-6), which was shown to have biological activities at 100-1000-fold lower concentrations than IL-6 in combination with sIL-6R. The secreted p84 glycoprotein was detected in the supernatant of transfected cells and was fully active on BAF3/gp130 cells, which respond to IL-6/sIL-6R but not to IL-6 alone. Administration of recombinant H-IL-6 to C57BL/6 mice resulted in a prolonged acute phase protein gene expression indicating long systemic persistence of the fusion protein. Transfected B16 cells (B16/H-IL6 cells…

Resveratrol, a chemopreventive agent, disrupts the cell cycle control of human SW480 colorectal tumor cells

2002

Resveratrol is a natural polyphenolic compound produced by a number of plants and found in high amount in peanuts, seeds, grapes or berries as source of human nutrition. Epidemiological studies strongly suggest that resveratrol may act as a cancer chemopreventive compound. The mechanism by which resveratrol inhibits cell proliferation was studied in human colorectal tumor SW480 cell line. The results show that resveratrol strongly inhibits cell proliferation at the micromolar range in a time- and dose-dependent manner. Resveratrol appears to block the cell cycle at the transition --> G2/M since inhibition of [(3)H]-thymidine incorporation is not observed, while there is an increase of the c…

Ethanol inhibits astroglial cell proliferation by disruption of phospholipase D-mediated signaling.

2002

The activation of phospholipase D (PLD) is a common response to mitogenic stimuli in various cell types. As PLD-mediated signaling is known to be disrupted in the presence of ethanol, we tested whether PLD is involved in the ethanol-induced inhibition of cell proliferation in rat cortical primary astrocytes. Readdition of fetal calf serum (FCS) to serum-deprived astroglial cultures caused a rapid, threefold increase of PLD activity and a strong mitogenic response; both effects were dependent on tyrosine kinases but not on protein kinase C. Ethanol (0.1-2%) suppressed the FCS-induced, PLD-mediated formation of phosphatidic acid (PA) as well as astroglial cell proliferation in a concentration…

Inhibition of DNA synthesis in chick embryo retinas, in vitro, by a factor from fetal bovine serum

1989

Fetal bovine serum inhibited deoxyribonucleic acid (DNA) synthesis in chick embryo retina explants. The inhibitory activity was precipitated from fetal bovine serum by 45% saturated ammonium sulfate and isolated by means of Sephadex G-100 and Bio-Gel P-60 columns as a peak with an apparent molecular weight of 7000 Da. DNA-inhibiting activity was heat- and acid-stable and was destroyed by dithiothreitol and alkaline treatment. The purified factor inhibited similarly both DNA synthesis and thymidine kinase activity; 50% inhibitory effect was found with 160 ng, 17 h after the addition into the incubation medium.

Down-regulation of wild-type β-catenin expression by interleukin 6 in human hepatocarcinoma HepG2 and leukemia HL60 cells: a possible role in the gro…

2000

Novel 3-Azaindolyl-4-arylmaleimides Exhibiting Potent Antiangiogenic Efficacy, Protein Kinase Inhibition, and Antiproliferative Activity

2012

Tumor growth and metastasis are highly associated with the overexpression of protein kinases (PKs) regulating cell growth, apoptosis resistance, and prolonged cell survival. This study describes novel azaindolyl-maleimides with significant inhibition of PKs, such as VEGFR, FLT-3, and GSK-3β which are related to carcinogenesis. Furthermore, these compounds exhibit high kinase selectivity and potent inhibition of angiogenesis and cell proliferation, offering versatile options in cancer treatment strategies.

Constitutive hsp70 is essential to mitosis during early cleavage of Paracentrotus lividus embryos: The blockage of constitutive hsp70 impairs mitosis

1999

Localization of constitutive hsp70 in eggs and early embryos of sea urchin Paracentrotus lividus is shown by means of in situ immunostaining. An accumulation of this protein is shown in the mitotic structures (asters, spindles and centrosomes). Microinjection of anti-hsp70 antibodies into eggs causes impairment of formation of mitotic structures and of cell division. This impairment goes from a complete mitotic block, to irregular mitotic apparatus formation with irregular cleavage, depending upon the antibody concentration. The localization of hsp70 after antibody microinjection is also described. Blockage of mitotic apparatus formation by nocodazole also blocks the concentration of hsp70 …

Exclusion of Saccharomyces kudriavzevii from a wine model system mediated by Saccharomyces cerevisiae.

2010

This study investigated the competition and potential hybrid generation between the species Saccharomyces cerevisiae and S. kudriavzevii in a wine-model environment. Our main goal was to understand why S. kudriavzevii has not been found in wine fermentations whilst their hybrids are present. Auxotrophic mutants (Ura(-) and Lys(-)) were used to favour the selection of hybrids and to specifically differentiate the two species in mixed fermentations carried out at different temperatures (17 °C, 24 °C and 31 °C). Both yeasts showed a reduction in their maximum specific growth rates in mixed fermentations, indicating a clear antagonistic effect between the two microorganisms. Temperature played …