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

Disseminating disease in neuroblastoma is of considerable clinical importance. Detection of circulating neuroblastoma cells using tyrosine hydroxylase (TH) as a tissue-specific target for reverse transcriptase-polymerase chain reaction has proved to be a sensitive and specific method for the detection of contaminating tumour cells in peripheral blood. The aim of this study was to report the early clinical observations made using this technology in neuroblastoma patient blood samples. A strong association was found between the detection of neuroblastoma cells in circulation with the detection of neuroblastoma in bone marrow. This method may be of use to monitor disease status and identify early signs of relapse in clinically disease-free patients. These results show that RT-PCR detection of TH mRNA is a relatively noninvasive, sensitive method for the detection of circulating tumour cells in neuroblastoma patients.
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PMID:Early clinical evaluation of neuroblastoma cell detection by reverse transcriptase-polymerase chain reaction (RT-PCR) for tyrosine hydroxylase mRNA. 757 66

The human neuroblastoma line, SK-N-SH, has been subcloned into SH-SY5Y, a neuroblast N cell line, and SH-EP, an epithelial Schwann S cell line. We have previously shown that SH-SY5Y neuroblastoma cells produce insulin-like growth factor II (IGF-II), which acts by an autocrine mechanism to stimulate cell growth. In the current study, we examined the effect of IGF-II on SH-EP neuroblastoma cells. Northern blot and reverse transcriptase-polymerase chain reaction analyses indicate that SH-EP cells do not produce IGF-I or IGF-II but express the type I and type II IGF receptors (IGF-IR and IGF-IIR). Cell surface expression of IGF-IR, assessed by fluorescence-activated sorting, was lower in SH-EP cells than in SH-SY5Y cells. Immunoprecipitation of IGF-IR, followed by anti-phosphotyrosine or anti-IGF-IR immunoblotting, demonstrated functional expression of these receptors in both cell types and confirmed the lower level of IGF-IR expression in SH-EP cells. IGF-II promoted SH-EP cell growth in the presence of low concentrations of calf serum (0.1-0.3%) or 10 ng/ml epidermal growth factor (EGF). IGF-II stimulation of SH-EP growth was eliminated by the IGF-IR blocking antibody (alpha IR-3) but not by an IGF-IIR blocking antibody. Stimulation of cell growth via this receptor was also indicated by the ligand specificity for IGF analogs and insulin (IGF-II approximately IGF-I approximately des(1-3)IGF-I >> insulin). These results indicate that in the presence of a permissive factor such as calf serum or EGF, IGF-II stimulates SH-EP cell growth via the IGF-IR. Collectively, these data suggest that within primary neuroblastomas, IGF-II may act as a paracrine factor to contribute to the promotion of S cell growth.
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PMID:Insulin-like growth factor-II as a paracrine growth factor in human neuroblastoma cells. 758 43

Neuroblastoma cell lines are useful for the investigation of neuronal receptor regulation since these cells display various neuronal features. Here we report the analysis of human AMPA and kainate receptor expression in four neuroblastoma cell lines (SK-N-MC, IMR-32, CHP 126 and NMB/N7). The reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated the presence of hGluR1, hGluR4 and EAA4 transcripts in all four cell lines whereas hGluR3 mRNA was undetectable. The pattern of expression of hGluR2, EAA1, EAA2, EAA3 and EAA5 was more complex and differed among the cell lines tested. Immunoblot analysis and electrophysiological recordings failed to demonstrate expression of hGluR1-hGluR4, EAA1/EAA2 proteins and the formation of functional AMPA/kainate receptor channels. These cell lines might provide a valuable model to study the transcriptional and post-transcriptional regulation of AMPA and kainate receptor expression.
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PMID:Expression of human glutamate receptors (GluR) in neuroblastoma cell lines. 761 80

C1 inhibitor was identified in human brain tissue by Western blotting and by immunohistochemistry using multiple antibodies to the native protein. The presence of C1 inhibitor mRNA was identified by reverse transcriptase-polymerase chain reaction analysis of brain mRNA extracts. The mRNA was also detected in cultured postmortem human microglia and in the IMR-32 human neuroblastoma cell line. Immunohistochemically, the native protein was detected in residual serum of capillaries and pyramidal neurons of both control and Alzheimer disease cases, as well as in occasional senile plaques of Alzheimer tissue. The reacted protein was detected on dystrophic neurites and neuropil threads in Alzheimer tissue by 4C3 monoclonal antibody, which recognizes a neoepitope following suicide inhibition. These data indicate that C1 inhibitor, a regulatory molecule controlling multiple inflammatory proteolytic cascades, is produced in normal brain. In Alzheimer disease, C1 inhibitor undergoes a prominent reaction in abnormal neuronal processes, such as dystrophic neurites and neuropil threads.
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PMID:Complement C1 inhibitor is produced by brain tissue and is cleaved in Alzheimer disease. 779 55

Adenosine triphosphate (ATP) regulates surfactant phospholipid secretion from alveolar type II cells by interacting with P2-purinoceptors on the alveolar type II cell surface. To further characterize regulation of surfactant secretion, we have cloned the type II cell P2u-purinoceptor and expressed a functional receptor in an unrelated cell line. The coding sequence of the P2u clone isolated from a type II cell cDNA library was 1.1 kb, encoding a putative protein of 374 amino acids. The putative protein demonstrated > 97% homology with the P2u-purinoceptor previously identified in the hybrid neuroblastoma x glioma cell line, NG 108-15, 87% homology to the recently cloned human P2u-purinoceptor, and 34% homology to the P2u-purinoceptor cloned from chicken brain. The putative type II cell P2u protein contains seven membrane-spanning domains, characteristic of G-protein-coupled receptors. The type II cell P2u-purinoceptor nucleotide sequence also demonstrated > 95% homology to the nucleotide sequence of the NG 108-15 clone. However, the type II cell cDNA also demonstrated presence of an additional 208 bp insert in the 5' untranslated region, which was not present in the NG 108-15 clone. Using reverse transcriptase polymerase chain reaction, we examined expression of the two different sizes of mRNA in various rat tissues. Only the larger type II cell mRNA was expressed in rat heart, kidney, lung, spleen, and testis, with no expression of P2u-purinoceptor mRNA noted in brain or liver. The smaller species of mRNA was only detected in mouse N18-TG2 cells, and these cells expressed a larger species as well, found in the rat tissues noted.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cloning and expression of the alveolar type II cell P2u-purinergic receptor. 781 68

HES-5 is a mammalian basic helix-loop-helix factor that has a distant sequence homology to the product of the Drosophila pair-rule gene hairy. HES-5 mRNA is present exclusively in the developing nervous system, but its level decreases as neural differentiation proceeds. In this study, to characterize the molecular mechanism of the neural-specific expression of HES-5 we isolated the mouse HES-5 gene. This gene consists of three exons, and Southern blot analysis shows that it is a single copy gene. The transcription initiation site, determined by primer extension and reverse transcriptase-mediated polymerase chain reaction, is located 26 nucleotides downstream of a TATAbox. Transient transfection analysis shows that the upstream region of the HES-5 gene can direct efficient expression in neural precursor cells and moderate expression in undifferentiated NCB20 neuroblastoma-brain hybrid cells but not in glioma or fibroblast cells. The moderate level of expression in NCB20 cells decreases when differentiation into neuron-like cells is induced. Further promoter analysis shows that this undifferentiated neural-specific expression is mediated by the multiple GC stretches present in the HES-5 promoter. Gel mobility shift analysis suggests the presence of a neural precursor cell-specific protein that binds to the GC stretches. These results raise the possibility that HES-5 expression in the developing nervous system is regulated by the GC stretch-binding protein.
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PMID:Structure and promoter analysis of the gene encoding the mouse helix-loop-helix factor HES-5. Identification of the neural precursor cell-specific promoter element. 783 1

Detectable levels of MAX messenger RNA were found in a set of human neuroblastoma tumors and established cell lines. MAX mRNA levels were independent of tumor stage and N-myc genomic amplification. By contrast, N-myc mRNA transcripts were detectable only in tumors with amplification of N-myc gene and in cell lines. Analysis by reverse transcriptase polymerase chain reaction and hybridization to specific oligodeoxynucleotide probes revealed approximately equal amounts of two MAX transcripts in all cases analyzed. Immunoprecipitations with a specific antibody to MAX detected two proteins of M(r) 21,000 and 22,000 in approximately equal amounts in all neuroblastoma lines regardless of N-myc amplification and/or expression. On the other hand, protein binding to the myc DNA consensus sequence correlated with N-myc expression in neuroblastoma cells. Thus, N-myc expression might be a limiting factor in the formation of the N-myc-MAX heterodimer in neuroblastomas.
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PMID:Lack of correlation between N-myc and MAX expression in neuroblastoma tumors and in cell lines: implication for N-myc-MAX complex formation. 817 35

Vasoactive intestinal peptide (VIP) has been considered as an autocrine growth factor in neuroblastomas. Pituitary adenylate cyclase activating polypeptides (PACAPs) are newly recognized members of the VIP family of neurohormones. As compared to VIP, PACAP has been reported to be biologically more potent and more efficient in tissues expressing selective PACAP receptors rather than common VIP/PACAP receptors. PACAPs and VIP interact with the same affinity and stimulate adenylate cyclase activity with the same efficacy and potency on the VIP receptors, but PACAPs act also on a more selective PACAP receptor that also recognizes VIP but with a 100- to 1,000-fold lower affinity. Thus, depending on the type of receptors expressed at a cell surface, PACAP may be more potent and efficient than VIP. The capacity of 22 surgical specimens of neuroblastomas and of 5 established cell lines to synthesize PACAP and VIP and to synthesize and express PACAP receptors and VIP receptors was studied. Using the reverse transcriptase-polymerase chain (RT-PCR) method with specific primers, we detected the mRNAs coding for PACAP and VIP in 19 and 3 out of 22 samples, respectively. PACAP mRNA was expressed in 3 of the 5 cell lines studied and VIP mRNA in 4. Using the same techniques, PACAP and VIP receptors mRNA were detected in 21, and 13 of the 22 tumor samples and in 5 and 1 of the cell lines studied, respectively. The expression of the PACAP receptor was demonstrated by direct binding studies and/or by the relative potency of PACAPs and VIP to stimulate adenylate cyclase activity in 16 of the 22 tumors and in all the cell lines. In addition, there was no correlation between tumor stage and the expression of mRNA coding for the peptides and the receptors. The present results demonstrated that PACAP could also be a candidate as an autocrine regulator of neuroblastoma which a higher activity than VIP.
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PMID:Pituitary adenylate cyclase activating peptide and its receptors are expressed in human neuroblastomas. 869 38

Childhood neuroblastoma tumours of the sympathetic nervous system show a remarkable clinical heterogeneity ranging from spontaneous regression to unfavourable outcome despite intensive therapy. Favourable neuroblastomas often express high levels of trkA mRNA, encoding the tyrosine kinase receptor for nerve growth factor. We have investigated mRNA expression for the neurotrophin receptor trkC in 23 primary neuroblastomas using a sensitive RNAase protection assay. TrkC expression was detected in 19 of these tumours at highly variable levels with a 300-fold difference between the highest and lowest values. Significantly higher levels of trkC mRNA were found in tumours from patients with favourable features such as low age (P < 0.012), favourable tumour stage (P < 0.012) and favourable prognosis (P < 0.05). Children with intermediate or high trkC mRNA expression had better prognosis compared with those with low or undetectable levels (83.3% vs 20%, P = 0.005). Further characterisation of trkC mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR) showed that mRNA encoding the full-length cytoplasmic tyrosine kinase domain of the receptor was only expressed in a subset of favourable tumours. These data show that favourable neuroblastomas may express the full trkC receptor while advanced tumours, in particular MYCN-amplified neuroblastoma, seem to either express no trkC or truncated trkC receptors of as yet unknown biological function. These data are suggestive of a role for trkC and its preferred ligand neutotrophin-3, NT-3, in neuroblastoma differentiation and/or regression.
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PMID:Expression of mRNA for the neurotrophin receptor trkC in neuroblastomas with favourable tumour stage and good prognosis. 879 81

The promoter region of the alpha-subunit of the calcium/calmodulin-dependent protein kinase II (alpha-CaMKII) gene was inserted into a beta-galactosidase (beta-gal) reporter plasmid, and beta-gal activities were examined in neuroblastoma (NB2a) and pheochromocytoma (PC12) cells after transient or stable transfections. The alpha-CaMKII promoter was 12- to 45-fold more active in NB2a compared with PC12 cells after transient or stable transfections. All-trans retinoic acid (RA) stimulated reporter gene expression at both protein and mRNA levels in transfected PC12 cells. RA increased the level of endogenous alpha-CaMKII mRNA in untransfected PC12 cells by 4.4-fold. The transcription initiation site(s) (TIS) of the alpha-CaMKII gene in PC12 cells and rat brain was examined by RNase protection assays (RPA) and reverse transcriptase PCRs. The TIS for the alpha-CaMKII/beta-gal reporter gene in transfected PC12 cells was indistinguishable from the TIS+1 in rat hippocampus. In contrast, the only detectable TIS for the alpha-CaMKII gene in untransfected PC12 cells was located near the ATG translation start codon, 147 nucleotides 3' to TIS+1 in hippocampus. This unusual TIS was also the predominant TIS in rat cerebellum. These results suggest that the alpha-CaMKII promoter may contain sequences that respond directly or indirectly to RA. In addition, the unusual TIS of the alpha-CaMKII gene in PC12 cells and rat cerebellum may contribute to the very low expression of this gene compared with that in hippocampus.
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PMID:Retinoic acid stimulates alpha-CAMKII gene expression in PC12 cells at a distinct transcription initiation site. 879 26


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