Targeting Bcl-2/Bcl-XL induces antitumor activity in uveal melanoma patient-derived xenografts.
PLoS ONE 9(1):e80836 (2014)
Uveal melanoma (UM) is associated with a high risk of metastases and lack of efficient therapies. Reduced capacity for apoptosis induction by chemotherapies is one obstacle to efficient treatments. Human UM is characterized by high expression of the anti-apoptotic protein Bcl-2. Consequently, re...
Analysis of sterol-regulatory element-binding protein 1c target genes in mouse liver during aging and high-fat diet.
Journal of Nutrigenetics and Nutrigenomics 6(2):107 (2013)
The sterol regulatory element-binding protein (SREBP) 1c contributes to the transcriptional coordination of cholesterol, fatty acid, and carbohydrate metabolisms. Alterations in these processes accelerate the progression of hepatic steatosis and insulin resistance during aging and obesity.
Blockade of α2-adrenoceptors induces Arc gene expression in rat brain in a glutamate receptor-dependent manner: a combined qPCR, in situ hybridisation and immunocytochemistry study.
Neuropharmacology 63(6):992 (2012)
Studies of 5-HT-glutamate interactions suggest that activation of brain 5-HT(2A) receptors leads to an AMPA receptor-mediated induction of the immediate early (activity-dependent) gene, Arc (Arg3.1). In this respect, noradrenaline-glutamate interactions are poorly characterised. Here we investig...
RhoA guanine exchange factor expression profile in arteries: evidence for a Rho kinase-dependent negative feedback in angiotensin II-dependent hypertension.
American Journal of Physiology - Cell Physiology 302(9):C1394 (2012)
Sustained overactivation of RhoA is a common component for the pathogenesis of several cardiovascular disorders, including hypertension. Although activity of Rho proteins depends on Rho exchange factors (Rho-GEFs), the identity of Rho-GEFs expressed in vascular smooth muscle cells (VSMC) and par...
Specific oncogenic activity of the Src-family tyrosine kinase c-Yes in colon carcinoma cells.
PLoS ONE 6(2):e17237 (2011)
c-Yes, a member of the Src tyrosine kinase family, is found highly activated in colon carcinoma but its importance relative to c-Src has remained unclear. Here we show that, in HT29 colon carcinoma cells, silencing of c-Yes, but not of c-Src, selectively leads to an increase of cell clustering a...
Exploring functional beta-cell heterogeneity in vivo using PSA-NCAM as a specific marker.
PLoS ONE 4(5):e5555 (2009)
The mass of pancreatic beta-cells varies according to increases in insulin demand. It is hypothesized that functionally heterogeneous beta-cell subpopulations take part in this process. Here we characterized two functionally distinct groups of beta-cells and investigated their physiological rele...
Preparation and affinity profile of novel nicotinic ligands.
Bioorganic & Medicinal Chemistry Letters 18(6):2188 (2008)
Novel nicotinic ligands, characterized by the presence of an amino substituted cyclopropane ring connected to a pyridine nucleus, are described. Pharmacological investigation revealed that these compounds exhibit highest affinity for the rat alpha4beta2 subtype of the nicotinic receptor with no ...
In vivo neuroprotective effects of the novel imidazolyl nitrone free-radical scavenger (Z)-alpha-[2-thiazol-2-yl)imidazol-4-yl]-N-tert-butylnitrone (S34176).
European Journal of Pharmacology 511(2-3):127 (2005)
Herein, we report an extensive investigation of the neuroprotective effects of the compound (Z)-alpha-[2-thiazol-2-yl)imidazol-4-yl]-N-tert-butylnitrone (S34176) and the prototypic nitrone alpha-phenyl-N-tert-butylnitrone (PBN), in different in vivo paradigms of neuronal degeneration. Administra...
Novel 2-alkylamino-1,4-benzoxazine derivatives as potent neuroprotective agents: structure-activity relationship studies.
Journal of Medicinal Chemistry 48(4):1282 (2005)
2-Alkylamino-substituted-1,4-benzoxazine derivatives, a new class of potential neuroprotective agents, were synthesized and examined for their intrinsic cytotoxicity and their capacity to inhibit oxidative stress-mediated neuronal degeneration in vitro. Through structure-activity relationship st...
Synthesis and pharmacological evaluation of new 1,2-dithiolane based antioxidants
European Journal of Medicinal Chemistry 38(1):1 (2003)
Molecules containing a dithiolane moiety are widely investigated due to their antioxidant properties. The archetypal representative of this class of compounds is lipoic acid and indeed the lipoic acid–dihydrolipoic acid couple is part of the antioxidant defence system of the cell. In the co...
Synthesis and pharmacological evaluation of new 1,2-dithiolane based antioxidants.
European Journal of Medicinal Chemistry 38(1):1 (2003)
Molecules containing a dithiolane moiety are widely investigated due to their antioxidant properties. The archetypal representative of this class of compounds is lipoic acid and indeed the lipoic acid-dihydrolipoic acid couple is part of the antioxidant defence system of the cell. In the course ...
Protective effect of the antioxidant 6-ethoxy-2,2-pentamethylen-1,2-dihydroquinoline (S 33113) in models of cerebral neurodegeneration
European Journal of Pharmacology 416(1):59 (2001)
In a previous study Dorey et al. [Bio. Org. Chem. Lett., 10 (2000) 935] a series of novel dihydroquinoline compounds were developed, based on the potent antioxidant 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline (ethoxyquin), and permitted the selection of the analogue 6-ethoxy-2,2-pentameth...
New quinolinic derivatives as centrally active antioxidants
Bioorganic & Medicinal Chemistry Letters 10(9):935 (2000)
A series of new 1,2-dihydro and 1,2,3,4-tetrahydroquinolines, synthesized from the corresponding propargylaniline intermediates, have been developed as antioxidants for the potential treatment of pathologies implicating central oxidative stress.
(S)-2,3-dihydro-[3,4]cyclopentano-1,2,4-benzothiadiazine-1,1-dioxide: (S18986-1) a positive modulator of AMPA receptors enhances (S)-AMPA-mediated [3H]noradrenaline release from rat hippocampal and frontal cortex slices
European Journal of Pharmacology 401(2):145 (2000)
The present study describes the effect of (
S)-2,3-dihydro-[3,4]cyclopentano-1,2,4-benzothiadiazine-1,1-dioxide (S18986-1), a positive allosteric modulator of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors with cognitive-enhancing effects, on (
A convenient extension of the Wessely–Moser rearrangement for the synthesis of substituted alkylaminoflavones as neuroprotective agents in vitro
Bioorganic & Medicinal Chemistry Letters 10(8):835 (2000)
A series of 8-alkylamino-5,7-dihydroxyflavones was prepared from chrysine via a seven step sequence. The synthesis of their 6-alkylamino isomers could be subsequently accomplished through a convenient extension of the Wessely–Moser rearrangement. These compounds were found to be efficient n...
Inhibition ofl-homocysteic acid and buthionine sulphoximine-mediated neurotoxicity in rat embryonic neuronal cultures with α-lipoic acid enantiomers
Brain Research 855(2):292 (2000)
In the present report, we have set out to investigate the potential capacity of both the oxidised and reduced forms of
RS-α-lipoic acid, and its separate
S-(−)enantiomers, to prevent cell death induced with
l-homocysteic acid (
l-HCA) and buthioni...
Synthesis of novelorthoalkylaminophenol derivatives as potent neuroprotective agentsin vitro
Bioorganic & Medicinal Chemistry Letters 9(20):2929 (1999)
A series of
orthoalkylaminophenol derivatives was synthesized and tested
in vitro with respect to their neuroprotective effect. Some of these compounds exhibited a potent antioxidant activity close to that of standard α-tocopherol.