Search results for "Organo"
showing 10 items of 1460 documents
BCL-XL inhibition induces an FGFR4-mediated rescue response in colorectal cancer
2022
The heterogeneous therapy response observed in colorectal cancer is in part due to cancer stem cells (CSCs) that resist chemotherapeutic insults. The anti-apoptotic protein BCL-XL plays a critical role in protecting CSCs from cell death, where its inhibition with high doses of BH3 mimetics can induce apoptosis. Here, we screen a compound library for synergy with low-dose BCL-XL inhibitor A-1155463 to identify pathways that regulate sensitivity to BCL-XL inhibition and reveal that fibroblast growth factor receptor (FGFR)4 inhibition effectively sensitizes to A-1155463 both in vitro and in vivo. Mechanistically, we identify a rescue response that is activated upon BCL-XL inhibition and leads …
Scandium(III) complexes of monophosphorus acid DOTA analogues: a thermodynamic and radiolabelling study with 44 Sc from cyclotron and from a 44 Ti/ 4…
2015
International audience; The complexation ability of DOTA analogs bearing one methylenephosphonic (DO3AP) or methylene-phosphinic (DO3AP PrA and DO3AP ABn) acid pendant arm toward scandium was evaluated. Stability constants of their scandium(III) complexes were determined by potentiometry combined with 45 Sc NMR spectroscopy. The stability constants of the monophosphinate analogues are somewhat lower than that of the Sc–DOTA complex. The phosphorus acid moiety interacts with trivalent scandium even in very acidic solutions forming out-of-cage complexes; the strong affinity of the phosphonate group to Sc(III) precludes stability constant determination of the Sc–DO3AP complex. These results we…
Colon Cancer Stem Cells Dictate Tumor Growth and Resist Cell Death by Production of Interleukin-4
2007
A novel paradigm in tumor biology suggests that cancer growth is driven by stem-like cells within a tumor. Here, we describe the identification and characterization of such cells from colon carcinomas using the stem cell marker CD133 that accounts around 2% of the cells in human colon cancer. The CD133(+) cells grow in vitro as undifferentiated tumor spheroids, and they are both necessary and sufficient to initiate tumor growth in immunodeficient mice. Xenografts resemble the original human tumor maintaining the rare subpopulation of tumorigenic CD133(+) cells. Further analysis revealed that the CD133(+) cells produce and utilize IL-4 to protect themselves from apoptosis. Consistently, trea…
Control of Cell Migration and Inflammatory Mediators Production by CORM-2 in Osteoarthritic Synoviocytes
2011
Background Osteoarthritis (OA) is the most widespread degenerative joint disease. Inflamed synovial cells contribute to the release of inflammatory and catabolic mediators during OA leading to destruction of articular tissues. We have shown previously that CO-releasing molecules exert anti-inflammatory effects in animal models and OA chondrocytes. We have studied the ability of CORM-2 to modify the migration of human OA synoviocytes and the production of chemokines and other mediators sustaining inflammatory and catabolic processes in the OA joint. Methodology/Principal Findings OA synoviocytes were stimulated with interleukin(IL)-1β in the absence or presence of CORM-2. Migration assay was…
Metachromatic staining and electron dense reaction of glycosaminoglycans by means of Cuprolinic Blue
1987
The cationic phthalocyanin-like dye Cuprolinic Blue, unlike phthalocyanin dyes such as Alcian Blue or Astra Blue, can definitely exhibit a clear metachromatic reaction with appropriate substrates. The application of Cuprolinic Blue to epoxy-embedded semithin sections revealed that mast cell cytoplasmic granules, goblet cell mucin and cartilage matrix stained in violet shades (metachromatic), whereas nuclear chromatin presented a bright blue coloration (orthochromatic). The metachromatic structures showed a high degree of contrast when ultrathin sections treated with Cuprolinic Blue were examined by electron microscopy. Cytophotometric measurements of stained components from the large intest…
Biomonitoring exposure assessment to contemporary pesticides in a school children population of Spain
2013
The exposure to pesticides amongst school-aged children (6-11 years old) was assessed in this study. One hundred twenty-five volunteer children were selected from two public schools located in an agricultural and in an urban area of Valencia Region, Spain. Twenty pesticide metabolites were analyzed in children's urine as biomarkers of exposure to organophosphate (OP) insecticides, synthetic pyrethroid insecticides, and herbicides. These data were combined with a survey to evaluate the main predictors of pesticide exposure in the children's population. A total of 15 metabolites were present in the urine samples with detection frequencies (DF) ranging from 5% to 86%. The most frequently detec…
[Gadolinium-containing contrast agents: Gadoterat-meglumine is safe in patients with chronic renal failure].
2014
Objective To prospectively compare the renal safety of meglumine gadoterate (Gd-DOTA)-enhanced magnetic resonance imaging (MRI) to a control group (unenhanced MRI) in high-risk patients. Methods Patients with chronic kidney disease (CKD) scheduled for MRI procedures were screened. The primary endpoint was the percentage of patients with an elevation of serum creatinine levels, measured 72 ± 24 h after the MRI procedure, by at least 25 % or 44.2 μmol/l (0.5 mg/dl) from baseline. A non-inferiority margin of the between-group difference was set at −15 % for statistical analysis of the primary endpoint. Main secondary endpoints were the variation in serum creatinine and eGFR values between base…
Inverse behaviour of "synaptic" ribbon and spherule numbers in the pineal gland of male guinea-pigs exposed to continuous illumination.
1986
There is increasing evidence that pineal “synaptic” ribbons are a heterogeneous population of organelles. In addition to “synaptic” ribbons (SR) sensu stricto, which consist of an electron-dense rod surrounded by electronlucent vesicles, “synaptic” spherules (SS) exist, the electrondense core of which is round and much wider than that of the SR. In the guinea-pig SR and SS numbers exhibit an inverse day/night rhythmicity. To gain more insight into the functional significance of SR and SS, guinea-pigs were exposed to continuous illumination for approximately 4 months (LL) and the respective structures in the pineal gland were quantitated under the electron microscope and compared with contro…
Comparative pharmacological activity of optical isomers of phenibut
2007
Phenibut (3-phenyl-4-aminobutyric acid) is a GABA (gamma-aminobutyric acid)-mimetic psychotropic drug which is clinically used in its racemic form. The aim of the present study was to compare the effects of racemic phenibut and its optical isomers in pharmacological tests and GABAB receptor binding studies. In pharmacological tests of locomotor activity, antidepressant and pain effects, S-phenibut was inactive in doses up to 500 mg/kg. In contrast, R-phenibut turned out to be two times more potent than racemic phenibut in most of the tests. In the forced swimming test, at a dose of 100 mg/kg only R-phenibut significantly decreased immobility time. Both R-phenibut and racemic phenibut showed…
Pancuronium improves the neuromuscular transmission defect of human organophosphate intoxication.
1990
Two patients with acute severe organophosphate intoxication showed (1) single evoked compound muscle action potentials (CMAP) with repetitive discharges and (2) prominent decremental responses of CMAP with 20 and 50 Hz supramaximal nerve stimulation. Following the intravenous injection of single small doses of pancuronium, marked improvement in these abnormalities occurred and persisted for several hours. We postulate that the physiologic improvement following low-dose pancuronium results from blockade of acetylcholine receptors, especially those located on the terminal axon responsible for antidromic backfiring.