Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amyloid beta peptide (Abeta), a proteolytic fragment of the amyloid precursor protein (APP), is a major component of the plaques found in the brain of Alzheimer's disease (AD) patients. These plaques are thought to cause the observed loss of cholinergic neurons in the basal forebrain of AD patients. In these neurons, particularly those of the nucleus basalis of Meynert, an up-regulation of 75kD-neurotrophin receptor (p75NTR), a nonselective neurotrophin receptor belonging to the death receptor family, has been reported. p75NTR expression has been described to correlate with beta-amyloid sensitivity in vivo and in vitro, suggesting a possible role for p75NTR as a receptor for Abeta. Here we used a human neuroblastoma cell line to investigate the involvement of p75NTR in Abeta-induced cell death. Abeta peptides were found to bind to p75NTR resulting in activation of NFKB in a time- and dose-dependent manner. Blocking the interaction of Abeta with p75NTR using NGF or inhibition of NFKB activation by curcumin or NFKB SN50 attenuated or abolished Abeta-induced apoptotic cell death. The present results suggest that p75NTR might be a death receptor for Abeta, thus being a possible drug target for treatment of AD.
 ...
PMID:Beta-amyloid binds to p57NTR and activates NFkappaB in human neuroblastoma cells. 985 63

By in situ hybridization, we show the ability of human neuroblastoma SY 5Y cells to synthesize apolipoprotein E (apoE) mRNA. This synthesis varied during cell NGF-differentiation: the mRNA level decreased during the first 4 days of NGF treatment (NGF 4 days) and then increased during the 3 following days (NGF 7 days). Furthermore, a treatment of 4-day NGF differentiated cells with exogenous apoE during 3 additional days induced a clear decrease in apoE mRNA synthesis when compared with control cells. This effect was more or less pronounced according to the apoE tested variants: apoE4 was more efficient to decrease the apoE mRNA synthesis as compared with the control cells than apoE3 which was itself more efficient than apoE2. These results suggest that apoE mRNA synthesis in human neuronal-type cells could be regulated by different mechanisms such as those induced by NGF- and apoE-treatments.
 ...
PMID:Synthesis of apolipoprotein E (ApoE) mRNA by human neuronal-type SK N SH-SY 5Y cells and its regulation by nerve growth factor and ApoE. 1032 90

Because of the known property of spontaneous regression in stage IVS of neuroblastoma all attempts are made to elucidate whether differentiation inducers possibly could be applied for neuroblastoma therapy. Here we examined the influence of retinoic acid (RA) in vitro on differentiation, proliferation and adhesion of 10 permanent and 4 primary cell lines as well as of several SCID-mouse tumour transplants. In general, after RA treatment morphologically different cell types which are characteristic for neuroblastoma cells have changed. N (neuronal)-type cells prolonged their neuronal processes, whereas S (epithelial, substrate-adherent, Schwann cell-like)-type cells lost their adherence to substratum and became apoptotic. Additionally, the reactions of all neuroblastoma cell lines with monoclonal antibodies against beta-tubulin (for neuronal cells) and glial fibrillary acidic protein (for epithelial cells) were determined. The anti-proliferative effect of all-trans-RA as well as 13-cis-RA was more profound in S-type cells (up to 40% in primary cell lines). To elucidate the role of adhesion molecules during neuronal cell differentiation, we have analysed the adhesion of neuroblastoma cells on poly-D-lysin-precoated plates under RA influence. While N-type cells displayed an increased adhesion, all S-type cell lines as well as all primary cell lines exhibited a reduced adhesion (IMR-5 and IMR-32: p < 0.001; JW, SR and PM: p < 0.05). RA treatment increased predominantly the tested antigens (HCAM, ICAM-1, NCAM, PECAM-1, VCAM-1, cadherin, FGF-R, IGF-R, NGF-R, TGF-beta/1, NF200, NF160, NF68, NSE, HLA-ABC) in all cell lines independently of their phenotypes (TGF-beta/1: p < 0.001; NF68: p < 0.01; PECAM-1 and NGF-R: p < 0.05). In recultured SCID-mouse-passaged tumour cells antigens were down-regulated (FGF-R: p < 0.01), but increased again after RA influence (TGF-beta/1: p < 0.05). In summary, the RA differentiation model demonstrates the possibility to interfere in cell adhesion and to diminish growth potential both in N-type as well as S-type neuroblastoma cells.
 ...
PMID:Differentiation, proliferation and adhesion of human neuroblastoma cells after treatment with retinoic acid. 1083 Jun 20

Neuroblastoma is the second-most common solid tumor in childhood. The majority of patients have a very poor outcome due to aggressive growth and metastatic spread. In contrast, in rare cases, spontaneous regression or differentiation towards a benign ganglioneuroma are observed. The mechanism leading to differentiation of neuroblastoma is of particular therapeutic interest. In this paper we report the results of our attempts to induce the expression of genes necessary for differentiation of neuroblastoma cells. TrkA codes for the high affinity receptor of NGF, a neurotrophin known to promote differentiation. Treatment with retinoic acid caused a 3-fold increase of the trkA expression in neuroblastoma cell lines. Neurofibromin, the gene product of the NF-1 gene, is involved in downregulation of the activity of ras-proteins. In contrast to immature neuronal tissues in mature brain, the type II isoform of neurofibromin is predominantly expressed. Retinoic acid was able to raise the proportion of type II NF-1 expressed in neuroblastoma cells.
 ...
PMID:Neuroblastoma: induction of differentiation (Part I). Basical science in pediatric surgery. 1087 72

NGF has been shown to support neuron survival by activating the transcription factor nuclear factor-kappaB (NFkappaB). We investigated the effect of NGF on the expression of Bcl-xL, an anti-apoptotic Bcl-2 family protein. Treatment of rat pheochromocytoma PC12 cells, human neuroblastoma SH-SY5Y cells, or primary rat hippocampal neurons with NGF (0.1-10 ng/ml) increased the expression of bcl-xL mRNA and protein. Reporter gene analysis revealed a significant increase in NFkappaB activity after treatment with NGF that was associated with increased nuclear translocation of the active NFkappaB p65 subunit. NGF-induced NFkappaB activity and Bcl-xL expression were inhibited in cells overexpressing the NFkappaB inhibitor, IkappaBalpha. Unlike tumor necrosis factor-alpha (TNF-alpha), however, NGF-induced NFkappaB activation occurred without significant degradation of IkappaBs determined by Western blot analysis and time-lapse imaging of neurons expressing green fluorescent protein-tagged IkappaBalpha. Moreover, in contrast to TNF-alpha, NGF failed to phosphorylate IkappaBalpha at serine residue 32, but instead caused significant tyrosine phosphorylation. Overexpression of a Y42F mutant of IkappaBalpha potently suppressed NFG-, but not TNF-alpha-induced NFkappaB activation. Conversely, overexpression of a dominant negative mutant of TNF receptor-associated factor-6 blocked TNF-alpha-, but not NGF-induced NFkappaB activation. We conclude that NGF and TNF-alpha induce different signaling pathways in neurons to activate NFkappaB and bcl-x gene expression.
 ...
PMID:Activation of nuclear factor kappaB and Bcl-x survival gene expression by nerve growth factor requires tyrosine phosphorylation of IkappaBalpha. 1126 66

The human neuroblastoma cell line SH-SY5Y can differentiate into a functional sympathetic neuronal phenotype when treated with low concentrations of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) in the presence of serum or defined growth factors. When TrkA is introduced into the cells, NGF also induces differentiation. In both cases, protein kinase C (PKC) is pivotal for induction and maintenance of the differentiated phenotype. We have recently shown that PKC activity is needed to enable the MAPK ERK to accumulate in the nucleus of SH-SY5Y cells and hence activate transcription. To find out whether this could be one reason for the PKC dependency in the differentiation process we have investigated the role of ERK during neuronal differentiation of these cells. The results show that ERK was needed for full upregulation of the neuronal marker genes NPY and GAP-43. However, ERK activity was not necessary for TPA-induced neurite formation. Neither was activation of ERK sufficient to promote neurite outgrowth. The results clearly show that there was no correlation between nuclear ERK activity, measured as SRE transactivation, and neurite formation in TPA-differentiated SH-SY5Y neuroblastoma cells.
 ...
PMID:A functional role for ERK in gene induction, but not in neurite outgrowth in differentiating neuroblastoma cells. 1128 40

Neuronal differentiation involves Rac and Cdc42 GTPases. alpha-Chimaerin, a Rac/Cdc42 regulator, occurs as alpha1- and alternatively spliced Src homology 2 (SH2) domain-containing alpha2-isoforms. alpha2-chimaerin mRNA was highly expressed in the rat embryonic nervous system, especially in early postmitotic neurons. alpha1-chimaerin mRNA was undetectable before embryonic day 16.5. Adult alpha2-chimaerin mRNA was restricted to neurons within specific brain regions, with highest expression in the entorhinal cortex. alpha2-chimaerin protein localized to neuronal perikarya, dendrites, and axons. The overall pattern of alpha2-chimaerin mRNA expression resembles that of cyclin-dependent kinase regulator p35 (CDK5/p35) which participates in neuronal differentiation and with which chimaerin interacts. To determine whether alpha2-chimaerin may have a role in neuronal differentiation and the relevance of the SH2 domain, the morphological effects of both chimaerin isoforms were investigated in N1E-115 neuroblastoma cells. When plated on poly-lysine, transient alpha2-chimaerin but not alpha1-chimaerin transfectants formed neurites. Permanent alpha2-chimaerin transfectants generated neurites whether or not they were stimulated by serum starvation, and many cells were enlarged. Permanent alpha1-chimaerin transfectants displayed numerous microspikes and contained F-actin clusters, a Cdc42-phenotype, but generated few neurites. In neuroblastoma cells, alpha2-chimaerin was predominantly soluble with some being membrane-associated, whereas alpha1-chimaerin was absent from the cytosol, being membrane- and cytoskeleton-associated, paralleling their subcellular distribution in brain. Transient transfection with alpha2-chimaerin mutated in the SH2 domain (N94H) generated an alpha1-chimaerin-like phenotype, protein partitioned in the particulate fraction, and in NGF-stimulated pheochromocytoma cell line 12 (PC12) cells, neurite formation was inhibited. These results indicate a role for alpha2-chimaerin in morphological differentiation for which its SH2 domain is vital.
 ...
PMID:alpha2-chimaerin, a Cdc42/Rac1 regulator, is selectively expressed in the rat embryonic nervous system and is involved in neuritogenesis in N1E-115 neuroblastoma cells. 1143 94

Since the discovery in 1954, NGF has been isolated from snake venoms and various tissues and organs of different animals. Recently, Lipps (2000b) reported the isolation of NGF from the human body fluids, saliva, serum, and urine. This investigation reports the isolation of NGF excreted by various types of cells from diverse origin, in serum free medium, proving that its presence is not restricted to neural cells. The established cell lines used were Chang's liver and neuroblastoma of human origin, Vero monkey origin, PC12 rat, and SP/2 mouse origin. The fully grown monolayers of the cells were maintained in serum free medium for 48 hours to excrete NGF in the medium and the cell free medium was concentrated. NGF from cell free concentrated medium for each cell line was isolated by high pressure liquid chromatography (HPLC) and was identified as described by Lipps (1998). The HPLC profiles for cell free concentrate from different types were observed to be similar. The NGF fraction was eluted last in the neutral pH (Fig. 1). The identified fraction for NGF from each cell line was further purified, which resolved into a single peak. The purified NGF was used to study the biological and immunological properties. The biological activities of NGFs from cell free medium were minuscule in comparison to the cobra venom derived NGF. The molecular weights of NGFs from cell free medium for all cell lines were identical, 36.0 kDa. Anti-human NGF reacted strongly immunologically with NGFs from human origin cells and poorly with rat and mouse. PC12 NGF antibody reacted immunologically only with PC12 NGF.
 ...
PMID:Isolation and characterization of nerve growth factor (NGF) excreted from cultured eukaryotic cells. 1149 61

Trophic molecules are key regulators of survival, growth and differentiation of neural cells. Neuronal cell type Neuro-2a is a good model to study development and molecules modulating this process, and retinoic acid (RA) and neurotrophins (NGF, BDNF, NT-3 and NT-4) have been shown to be active in this modulation. The purpose of the present study was the functional analysis of these trophic molecules in our short-term bioassay of Neuro-2a cells, an immortalised murine neuroblastoma cell line. Through cell counting, image process and arithmetic combination of digital parameters of treated and untreated cultures, we show that RA inhibits growth and induces morphological neuronal phenotype of treated cells. Through DNA labelling with BrdU we also show that NGF, BDNF, and NT-3 increase survival and proliferation of cells, grown in serum-deprived media. From these results we conclude that neurotrophins have manifest trophic effects on cells improving survival, growth and proliferation and we also confirm the growth arrest and differentiation properties of RA on Neuro-2a cells.
 ...
PMID:Growth inhibition, morphological differentiation and stimulation of survival in neuronal cell type (Neuro-2a) treated with trophic molecules. 1151 98

Guanine nucleotide exchange factors from the Dbl family are proto-oncogenic proteins that activate small GTPases of the Rho family. Here we report the characterization of GEF720, a novel Dbl-like protein related to p115Rho-GEF. GEF720 activated RhoA both in our recently developed Yeast Exchange Assay and in biochemical in vitro exchange assays. GEF720 induced RhoA dependent assembly of actin stress fibers in REF52 fibroblastic cells. In NIH3T3 cells this Dbl-like protein elicited formation of transformation foci with a morphology similar to RhoA-V14 induced foci. In the PC12 neuron-like cell line, expression of GEF720, whose mRNA is brain specific, inhibited NGF-induced neurite outgrowth. Finally, GEF720 gene is located on human chromosome 1 on band 1p36, between Tumor Protein 73 and Tumor Necrosis Factor Receptor 12, two genes rearranged in many neuroblastoma cell lines. Together, these results show that this new Dbl related protein, GEF720, is an exchange factor that can directly activate RhoA in vivo and is potentially involved in the control of neuronal cell differentiation. GEF720 is also a new candidate gene involved in the progression of neuroblastoma and developmental abnormalities associated with rearrangements in the 1p36 chromosomal region.
 ...
PMID:The gene for a new brain specific RhoA exchange factor maps to the highly unstable chromosomal region 1p36.2-1p36.3. 1170 60


<< Previous 1 2 3 4 5 6 7 8 9 Next >>