Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MBA-15, a marrow stromal-derived cell line, was shown to express an estrogen receptor. This finding was confirmed by in situ hybridization and receptor binding assay. An exposure to estrogen (10(-12)-10(-6) M) in a dose response manner resulted in a decrease of cell proliferation as measured by MTT assay. Cell function was measured by enzymatic activities of two osteoblastic markers, CD10/NEP and alkaline phosphatase. These enzymatic activities were elevated following the estrogen treatment. This model enabled direct evaluation of the estrogen effect on stromal osteoblast cells.
 ...
PMID:The expression of estrogen receptor and estrogen effect in MBA-15 marrow stromal osteoblasts. 885 24

The betacyte is a genetically engineered insulin-secreting liver cell line that is glucose responsive. Whether this cell is affected by specific beta-cell toxins is unknown. To explore this possibility we exposed these cells and those from the NIT-1 beta-cell line (positive controls) to the toxins streptozotocin (STZ, 2.5-20 mM), alloxan (ALL, 2.5-20 mM), and pentamidine (PENT, 10(-6)-1 mM). STZ and ALL were added for 1 h and pentamidine for 24 h. Insulin secretion from betacytes during a period of 5 h after removal of the toxin was inhibited only by pentamidine; all agents were inhibitory to NIT-1 cells. Glucose metabolism, as determined by a colorimetric MTT reduction assay, was adversely affected in betacytes by ALL (20 mM) and PENT (1 mM), and in NIT-1 cells by STZ (20 mM) as well as by ALL (2.5 mM) and PENT (1 mM). The magnitude of inhibition was less for the betacytes-58 v. 99%. Confluence of cells in culture wells and cell viability as assessed by the fluorochromes propidium iodide and acridine orange was reduced to a lesser extent for the betacytes than for the NIT-1 cells. The metabolic and microscopic effects of the toxins were unchanged in the betacyte from those in the liver cell line, HEP G2, from which the betacyte was engineered. These results of general resistance of the betacyte to beta-cell toxins with differing modes of action offer hope that this cell, or cells created in a similar manner from primary hepatocytes, may be at least partly resistant to the adverse effect of beta-cell toxins involved in autoimmune destruction of the pancreas. This increases the potential of the use of these cells for reversal of diabetes.
 ...
PMID:Effect of beta-cell toxins on genetically engineered insulin-secreting cells. 921 49

In this paper, we present evidence that Ginsenoside-Rs3 (G-Rs3), a new diol-type ginseng saponin isolated from the roots of Panax ginseng C.A. Meyer, efficiently arrests the cell cycle at the G1/S boundary at lower doses, 0.1-5 microM, but induces apoptosis at higher doses, 10-25 microM, the effects of which were associated with selectively elevating protein levels of p53 and p21WAF1 in SK-HEP-1 cells. The cell growth suppressive and apoptosis inducing effects were confirmed by MTT assays together with flow cytometric analyses, morphological changes and DNA fragmentation. Immunoblotting showed that G-Rs3 significantly elevated protein levels of p53 and p21WAF1 prior to inducing apoptosis, while it did not elevate those of cyclin E, cyclin A, p27Kip1, and PCNA. Immune complex kinase assays showed that G-Rs3 downregulated the activities of both cyclins E- and A-associated kinases. Collectively, we suggest that G-Rs3 selectively elevates protein levels of p53 and p21WAF1 and hence downregulates the activities of the cyclin-dependent kinases, resulting in cell cycle arrest at the G1/S boundary. We also propose that apoptosis induced by G-Rs3 is related to the elevations of p53 and p21WAF1 in the cells.
 ...
PMID:Ginsenoside-Rs3, a new diol-type ginseng saponin, selectively elevates protein levels of p53 and p21WAF1 leading to induction of apoptosis in SK-HEP-1 cells. 1022 87

Block copolymer micelles formed from copolymers of poly(caprolactone)-b-poly(ethylene oxide) (PCL-b-PEO) were investigated as a drug delivery vehicle for dihydrotestosterone (DHT). The physical parameters of the PCL-b-PEO micelle-incorporated DHT were measured, including the loading capacity of the micelles for DHT, the apparent partition coefficient of DHT between the micelles and the external medium and the kinetics of the release of DHT from the micelle solution. The MTT survival assay was used to assess the in vitro biocompatibility of PCL-b-PEO micelles in HeLa cell cultures. The biological activity of the micelle-incorporated DHT was evaluated in HeLa cells which had been co-transfected with the expression vectors for the androgen receptor and the MMTV-LUC reporter gene. The PCL-b-PEO micelles were found to have a high loading capacity for DHT and the release profile of the drug from the micelle solution was found to be a slow steady release which continued over a 1-month period. The biological activity of the micelle-incorporated DHT was found to be fully retained.
 ...
PMID:Polycaprolactone-b-poly(ethylene oxide) copolymer micelles as a delivery vehicle for dihydrotestosterone. 1060 23

To study cellular signaling factors responsible for the susceptibility of human cells to cell proliferation inhibition by anticancer drugs, human RSa cell line and its ultraviolet-resistant derivative UVr-1 were compared with respect to their sensitivity to the anti-proliferative effects of mitomycin C (MMC), 5-fluorouracil, nimustine (ACNU), cisplatin, pirarubicin (THP), bleomycin, methotrexate and ifosfamide. RSa cells were found to be highly sensitive to MMC by MTT assay compared to UVr-1 cells. The half maximum inhibition concentration of MMC against proliferation of RSa cells was approximately 100 ng/ml while that of UVr-1 cells was greater than 1 microgram/ml. There was no significant difference observed between RSa and UVr-1 cells in the sensitivity to other seven drugs examined. Analysis by flow cytometry revealed that the cell cycle of RSa was completely blocked at the G2/M phase 40 h after treatment with MMC at a concentration of 100 ng/ml whereas a substantial proportion of UVr-1 cells was not arrested at that phase even in the presence of MMC. Further immunoblot analysis on MMC-induced signal transduction showed that the amounts of phosphorylated ERK MAP kinases were increased in UVr-1 cells to a greater extent than those in RSa cells after treatment with MMC for longer than 2 h. However, the increase in p21Cip1 was observed in RSa cells 1 h after addition of MMC but was not observed in UVr-1 cells. These distinct signaling pathways might account for the differences in sensitivity to MMC between RSa and UVr-1 cells.
 ...
PMID:Differential sensitivity to mitomycin C between human RSa cell line and its derivative UVr-1. 1062 31

Recent literature by Fan et al (1993) demonstrated that addition of cisplatin and monoclonal antibody to the epidermal growth factor receptor (EGFR MAb) of the human squamous cell carcinoma (SCC), A431, eradicated gross tumors in nude mice. To determine whether a combination of either cisplatin or 5-fluorouracil (5-FU) with EGFR MAb could affect an SCC other than the A431 tumor model, an assay using 2 human tongue SCC cell lines, BroTo and SCC-25, was performed. Cells were pretreated with 1.25 microgram/mL cisplatin or 10 microgram/mL 5-FU. After a 4-hour incubation period, cisplatin-treated cells were washed with phosphate-buffered saline solution. Various concentrations of EGFR MAb were then added, and after a 24-hour incubation period, an MTT cell growth assay was performed. SCC-25 cells exhibited a greater decrease in growth with the addition of 16 nmol/L EGFR MAb to cisplatin compared with the cytotoxicity of cisplatin alone (P < 0.001). However, this combination did not produce similar results with BroTo cells (P > 0.05). The combination of EGFR MAb and 5-FU produced a growth inhibition versus control (unexposed cells) in both cell lines (P < 0.05). These findings suggest the possible augmentation of the activity of chemotherapeutic agents, cisplatin and/or 5-FU, with the addition of EGFR MAb on SCC cell lines other than A431.
 ...
PMID:Antiepidermal growth factor receptor antibodies augment cytotoxicity of chemotherapeutic agents on squamous cell carcinoma cell lines. 1062 87

Amphiphilic block copolymers composed of relatively hydrophilic PEO-PPO-PEO block copolymer (Pluronic) and poly (epsilon-caprolactone) with hydrophobic character were synthesized by ring-opening polymerization of epsilon-caprolactone in the presence of PEO-PPO-PEO block copolymer using stannous octoate as a catalyst. Pluronic/PCL block copolymeric nanospheres with core-shell structure were prepared by dialysis method. They showed the average diameter of 116-196 nm depending on the type of copolymer. All the nanosphere samples exhibited a narrow size distribution. The critical micelle concentrations of Pluronic/PCL amphiphilic block copolymers determined by fluorescence spectroscopy were lower than that of the common low molecular weight surfactant. Their core-shell structure was confirmed by 1H NMR spectroscopy. Pluronic/PCL block copolymeric nanospheres exhibited the reversible change of size depending on the temperature. Release behaviors of indomethacin from Pluronic/PCL block copolymeric nanospheres also showed temperature dependence and a sustained release pattern. In addition, cytotoxicity test using an MTT assay method revealed that these indomethacin-loaded Pluronic/PCL nanospheres could remarkably reduce the cell damage compared with the unloaded free indomethacin.
 ...
PMID:Poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)/poly(epsilon-caprolactone) (PCL) amphiphilic block copolymeric nanospheres. II. Thermo-responsive drug release behaviors. 1069 93

1. Epidermal growth factor (EGF) is produced by growth hormone (GH) cells and gonadotropes in normal pituitary cell populations. The studies were initiated to determine whether EGF is a paracrine or autocrine regulator of gonadotrope function. 2. The first group of studies tested for the presence of EGF receptors in gonadotropes from cycling female rats by immunolabelling. Expression varied with the stage of the cycle. At the highest point (metoestrus), only a few EGF target cells are gonadotropes, identified by their content of luteinizing hormone (LH)-beta mRNA. Expression by gonadotropes then increased to reach a peak of 50% of cells during pro-oestrus. 3. Studies investigating the regulation of expression of EGF receptor (R) showed that all culture conditions (in media with or without serum) and EGF itself both stimulated expression of the receptor by gonadotropes in populations from oestrus or metoestrus rats. Gonadotropin-releasing hormone (GnRH) also stimulated EGFR expression in follicle-stimulating hormone (FSH) gonadotropes from oestrus animals. Additional tests of expression of immediate early genes (c-fos) showed that, after 15 min, EGF stimulated expression in cells with FSH antigens. 4. Epidermal growth factor also stimulated gonadotrope proliferation, as detected by the MTT cell growth/cell death assays and bromodeoxyuridine uptake by gonadotropes during the S phase (DNA synthesis) of the cell cycle. 5. Epidermal growth factor and GnRH both stimulated a significant increase in the percentage of mitotic gonadotropes. Epidermal growth factor may be an autocrine or a paracrine growth factor to maintain and develop the gonadotrope population and EGF may also be involved in early differentiation events that prepare cells to support the LH surge.
 ...
PMID:Sites of epidermal growth factor synthesis and action in the pituitary: paracrine and autocrine interactions. 1123 36

The function of VEGF in laryngeal carcinoma was studied by observing either the expressions of VEGF and its receptor flk-1 in laryngeal carcinoma, or the effect of anti-VEGF antibody and anti-VEGF receptor antibody on the growth of human laryngeal cancer cell line HEP-2 in vitro. The expression of VEGF and flt in the specimen of laryngeal carcinoma were determined by standardized immunohistochemistry (Elite ABC method). Anti-VEGF antibody and anti-VEGF receptor antibody were also added at various concentrations to the culture medium, respectively, and the growth of HEP-2 was measured by MTT assay. The immunohistochemical staining showed that the expressions of VEGF and flt were detected both in carcinoma cells and endothelial cells. The growth of HEP-2 cell line in vitro was suppressed when adding various concentration of anti-VEGF antibody and anti-VEGF receptor antibody to the culture medium. The laryngeal cancer cells can secret VEGF and there exists VEGF-binding site on laryngeal cancer cell. Both blockading VEGF with anti-VEGF antibody and blockading VEGF-binding site with anti-VEGF receptor antibody could inhibit HEP-2 growth.
 ...
PMID:[The influence of vascular endothelial growth factor and its receptor on the growth of laryngeal cancer cell]. 1126 58

A group of unnatural 1-(2-deoxy-beta-D-ribofuranosyl)-2,4-difluorobenzenes having a variety of C-5 two-carbon substituents [-C...C-X, X = I, Br; -C...CH; (E)-CH=CH-X, X = I, Br; -CH=CH2; -CH2CH3; -CH(N3) CH2Br], designed as nucleoside mimics, were synthesized for evaluation as anticancer and antiviral agents. The 5-substituted (E)-CH=CH-I and -CH2CH3 compounds exhibited negligible cytotoxicity in a MTT assay (CC50 = 10(-3) to 10(-4)M range), relative to thymidine (CC50 = 10(-3) to 10(-5)M range), against a variety of cancer cell lines. In contrast, the C-5 substituted -C...C-I and -CH(N3)CH2Br compounds were more cytotoxic (CC50 = 10(-5) to 10(-6)M range). The -C...C-I and -CH2CH3 compounds exhibited similar cytotoxicity against non-transfected (KBALB, 143B) and HSV-1 TK+ gene transfected (KBALB-STK, 143B-LTK) cancer cell lines expressing the herpes simplex virus type 1 (HSV-1) thymidine kinase gene (TK+). This observation indicates that expression of the viral TK enzyme did not provide a gene therapeutic effect. The parent group of 5-substituted compounds, that were evaluated using a wide variety of antiviral assay systems [HSV-1, HSV-2, varicella-zoster virus (VZV), vaccinia virus, vesicular stomatitis, cytomegalovirus (CMV), and human immunodeficiency (HIV-1, HIV-2) viruses], showed that this class of unnatural C-aryl nucleoside mimics are inactive and/or weakly active antiviral agents.
 ...
PMID:Synthesis of 1-(2-deoxy-beta-D-ribofuranosyl)-2,4-difluoro-5-substituted-benzenes: "thymine replacement" analogs of thymidine for evaluation as anticancer and antiviral agents. 1130 62


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