Search results for "Growth Inhibitors"
showing 10 items of 24 documents
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.
Monitoring of anti-vaccine CD4 T cell frequencies in melanoma patients vaccinated with a MAGE-3 protein.
2005
Abstract Quantitative evaluation of T cell responses of patients receiving antitumoral vaccination with a protein is difficult because of the large number of possible HLA-peptide combinations that could be targeted by the response. To evaluate the responses of patients vaccinated with protein MAGE-3, we have developed an approach that involves overnight stimulation of blood T cells with autologous dendritic cells loaded with the protein, sorting by flow cytometry of the T cells that produce IFN-γ, cloning of these cells, and evaluation of the number of T cell clones that secrete IFN-γ upon stimulation with the Ag. An important criterion is that T cell clones must recognize not only stimulat…
CtIP silencing as a novel mechanism of tamoxifen resistance in breast cancer.
2007
AbstractAcquired resistance to the antiestrogen tamoxifen constitutes a major clinical challenge in breast cancer therapy. However, the mechanisms involved are still poorly understood. Using serial analysis of gene expression, we identified CtIP, a BRCA1- and CtBP-interacting protein, as one of the most significantly down-regulated transcripts in estrogen receptor α–positive (ER+) MCF-7 tamoxifen-resistant breast cancer cells. We further confirmed the association of CtIP down-regulation with tamoxifen resistance in an additional ER+ breast cancer line (T47D), strengthening the relevance of the phenomenon observed. In additional studies, we found CtIP protein expression in a majority of ER+ …
Regulation of the type II oncostatin M receptor expression in lung-derived epithelial cells
1998
AbstractOncostatin M (OSM) is a potent modulator of human lung-derived epithelial cell function. This cytokine binds two distinct receptor complexes: type I OSM receptor which is also a functional receptor for leukemia inhibitory factor (LIF), and type II OSM-specific receptor. The role of these two distinct receptors in mediating the response of individual cell types to OSM has not been delineated. In contrast to LIF, OSM induces synthesis of α1-antichymotrypsin and α1-antiproteinase inhibitor in lung-derived epithelial cells. The differential responsiveness to LIF and OSM suggested that the response of lung epithelial cells to OSM may be mediated by the OSM-specific receptor. Therefore, w…
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.
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…
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…
Transformation of the dermatophyte Trichophyton mentagrophytes to hygromycin B resistance.
1989
A transformation system for the ringworm-producing dermatophyte Trichophyton mentagrophytes has been developed. The system employs the plasmid pHIS, which contains a bacterial hygromycin B phosphotransferase gene linked to Cochliobolus heterostrophus regulatory sequences (B. G. Turgeon, R. C. Garber, and O. C. Yoder, Mol. Cell. Biol. 7:3297-3305, 1987). This plasmid confers hygromycin B resistance to T. mentagrophytes. The DNA was stably integrated into the fungal genome, and the number and sites of integrations varied among transformants. Transformant clones were capable of infecting guinea pigs. This system opens the way for the molecular genetic analysis of the interaction of T. mentagro…
Protective role of nuclear factor of activated T cells 2 in CD8+ long-lived memory T cells in an allergy model
2007
Background The transcriptional regulation of cytokines released and controlled by memory T cells is not well understood. Defective IFN-γ production in allergic asthma correlates in human beings with the risk of wheezing in childhood. Objective To understand the role of the transcription factor nuclear factor of activated T cells 2 (NFATc2) in memory and effector T cells in the airways in experimental allergic asthma. Methods We used murine models of allergic asthma and adoptive cell transfer of fluorescence-activated sorted cells in a disease model. Results Mice lacking NFATc2 developed an increase in airway hyperresponsiveness (AHR), remodeling, and serum IgE levels on ovalbumin sensitizat…