Candidate Factors (candidate + factor)

Distribution by Scientific Domains


Selected Abstracts


Amphiregulin is a factor for resistance of glioma cells to cannabinoid-induced apoptosis

GLIA, Issue 13 2009
Mar Lorente
Abstract Gliomas, one of the most malignant forms of cancer, exhibit high resistance to conventional therapies. Identification of the molecular mechanisms responsible for this resistance is therefore of great interest to improve the efficacy of the treatments against these tumors. ,9-Tetrahydrocannabinol (THC), the major active ingredient of marijuana, and other cannabinoids inhibit tumor growth in animal models of cancer, including glioma, an effect that relies, at least in part, on the ability of these compounds to induce apoptosis of tumor cells. By analyzing the gene expression profile of two sub-clones of C6 glioma cells with different sensitivity to cannabinoid-induced apoptosis, we found a subset of genes with a marked differential expression in the two sub-clones. Furthermore, we identified the epidermal growth factor receptor ligand amphiregulin as a candidate factor to mediate the resistance of glioma cells to cannabinoid treatment. Amphiregulin was highly overexpressed in the cannabinoid-resistant cell line, both in culture and in tumor xenografts. Moreover, in vivo silencing of amphiregulin rendered the resistant tumors xenografts sensitive to cannabinoid antitumoral action. Amphiregulin expression was associated with increased extracellular signal-regulated kinase (ERK) activation, which mediated the resistance to THC by blunting the expression of p8 and TRB3,two genes involved in cannabinoid-induced apoptosis of glioma cells. Our findings therefore identify Amphirregulin as a factor for resistance of glioma cells to THC-induced apoptosis and contribute to unraveling the molecular bases underlying the emerging notion that targeted inhibition of the EGFR pathway can improve the efficacy of antitumoral therapies. © 2009 Wiley-Liss, Inc. [source]


Proteomic analysis of nuclear factors binding to an intronic enhancer in the myelin proteolipid protein gene

JOURNAL OF NEUROCHEMISTRY, Issue 5 2008
Anna Dobretsova
Abstract The myelin proteolipid protein gene (Plp1) encodes the most abundant protein found in CNS myelin, accounting for nearly one-half of the total protein. Its expression in oligodendrocytes is developmentally regulated , peaking during the active myelination period of CNS development. Previously, we have identified a novel enhancer (designated ASE) in intron 1 DNA that appears to be important in mediating the surge of Plp1 gene activity during the active myelination period. Evidence suggests that the ASE participates in the formation of a specialized multi-protein/DNA complex called an enhanceosome. The current study describes an optimized, five-step, DNA affinity chromatography purification procedure to purify nuclear proteins from mouse brain that bind to the 85-bp ASE sequence, specifically. Electrophoretic mobility shift assay analysis demonstrated that specific DNA-binding activity was retained throughout the purification procedure, resulting in concomitant enrichment of nucleoprotein complexes. Identification of the purported regulatory factors was achieved through mass spectrometry analysis and included over 20 sequence-specific DNA-binding proteins. Supplementary western blot analyses to determine which of these sequence-specific factors are present in oligodendrocytes, and their developmental and regional expression in whole brain, suggest that Pur, and Pur, rank highest among the candidate factors as constituents of the multi-protein complex formed on the ASE. [source]


Factors associated with the development of panic attack and panic disorder: Survey in the Japanese population

PSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 2 2005
HISANOBU KAIYA md
Abstract, Environmental factors, in addition to genetic factors, may be related to the development of panic attack (PA) and panic disorder (PD). Previous studies suggested that there may be seasonal variation in the onset of PA/PD and possibly a higher prevalence of PA/PD in colder areas. Also observed were lactate-induced PA and elevated serum cholesterol in PD patients. These suggest that living environment and lifestyle, such as weather conditions, preference of food and physical exercise, might play a role in the occurrence of PA and PD. The present study explored the association of such candidate factors with the development of PA and PD in 4000 Japanese subjects, using a questionnaire. The subjects were recruited from the general population of Japan, using stratified random sampling. Logistic regression with stepwise selection of variables was employed for statistical analysis. Variables including ,dislike of physical exercise', mostly in female subjects, and ,living in areas with longer winter', in male subjects, were suggested for associations with PA and PD among the candidate factors. The result is preliminary but indicates that lifestyle such as like/dislike of physical exercise and environmental factors including weather conditions could play a partial role in the development of PA and PD. Further investigations are required before firm conclusions can be reached. [source]


Protein screening in vitreous samples of patients with retinal vein occlusion

ACTA OPHTHALMOLOGICA, Issue 2009
HT AGOSTINI
Purpose The aim of the study was to identify proteins involved in the pathogenesis of retinopathy after retinal vein occlusion. In retinal vein occlusion, proteins penetrate from leaky vessels into the vitreous. Alternatively, retinal cells produce protein factors and release them into the vitreous. Methods Vitreous and plasma samples of patients with retinal vein occlusion or macular pucker / macular hole were analyzed by antibody microarrays and ELISA. Results An antibody based microarray with more than 500 target for screening vitreous samples initially was less enlightening than antibody arrays providing the possibility to quantify up to 30 proteins in an ELISA-like microassay. Standard curves of antibody microarrays are as linear as those of ELISAs. VEGF values were similar to values measured by ELISA. Conclusion In our screen, we found some candidate factors which are currently investigated for their potential of influencing retinopathy after retinal vein occlusion. The use of microarrays to identify protein factors involved in retinal disease in the vitreous will be discussed. [source]