Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Intracisternal A particle preparations from a murine neuroblastoma cell line (N18) and from a mineral oil-induced murine plasmacytoma (MOPC-104E) contain both an endogenous RNA-dependent DNA polymerase activity and high molecular-weight polyadenylic acid (poly[A])-containing RNA. The DNA polymerase activity is stimulated by oligo(dG)-poly(C) and oligo(dT)-poly(A) and to a lesser extent by oligo(dT)-poly(dA), in agreement with previous reports. The high-molecular-weight RNA is predominantly 35S and contains a poly(A) tract of approximately 220 nucleotides as judged by polyacrylamide gel electrophoresis. Small amounts of 70S RNA are also present. This RNA preparation contains RNA homologous to RNA from type-C particles, as judged by molecular hybridization experiments. However, since this RNA derives only in part from A-particles and in part from other cellular RNA, hybridization of A-particle endogenously synthesized DNA or reverse transcripts of A-particle RNA to purified type C viral 70S RNA may more accurately reflect the relationship of A-particle RNA to RNA from C-particles. None of these DNA transcripts hybridizes significantly to C-particle 70S RNA, although MOPC and N18 DNA transcripts share significant homology. Our interpretation of these results is that murine intracisternal A particles are not closely related genetically to the tested murine type C viruses, although an alternate possibility is that all the A-particle DNA transcripts are copied from only a small part of the genome, which is unrelated to C-particle RNA.
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PMID:Murine intracisternal type A particles: a biochemical characterization. 5 37

The secretion of insulin-like growth-factor-binding proteins (IGFBPs) and expression of the genes encoding IGFBP-1, IGFBP-2 and IGFBP-3 have been studied in a panel of cell lines derived from breast carcinomas, Wilms' tumour, neuroblastoma, retinoblastoma, colon carcinoma, liver adenocarcinoma, Burkitt's lymphoma and a non-small-cell lung carcinoma. All cell lines, with the exception of the Burkitt's lymphoma cell line, secreted IGFBPs, as detected by affinity labelling. A 34-kDa BP was present in the conditioned media of all IGFBP-secreting cell lines, whereas BPs ranging from 18 kDa to 53 kDa were variably secreted. All IGFBP-secreting cell lines expressed the IGFBP-2 gene as determined by Northern blot analysis. The Wilms' tumour, the neuroblastoma and the retinoblastoma cell line expressed the IGFBP-2 gene only. All other cell lines, with the exception of the Burkitt's lymphoma, expressed the IGFBP-2 gene and, in addition, either the IGFBP-1 gene and/or the IGFBP-3 gene. IGFBP-1 gene expression could be detected by reverse transcriptase polymerase chain reaction only. IGFBP-3 gene expression was detected by Northern blot analysis, but transcripts were less abundant than IGFBP-2 mRNAs. These findings indicate that the expression of multiple BP genes and the secretion of BPs may be a common property of tumour cells.
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PMID:Insulin-like growth-factor-binding protein gene expression and protein production by human tumour cell lines. 137 87

The presence of circulating tumor cells in patients with localized or disseminated neuroblastoma may be a significant prognostic factor at diagnosis and may antedate the detection of relapse by other diagnostic studies. We report the development of a highly sensitive detection assay for circulating neuroblasts based on the reverse transcriptase-polymerase chain reaction (RT-PCR), using the neuroendocrine protein gene product 9.5 (PGP 9.5) as the tumor marker. Analysis of RT-PCR products by agarose gel electrophoresis demonstrated that neuroblastoma cell lines were uniformly positive, whereas peripheral blood mononuclear cells were negative. Alkaline Southern blotting with a PGP 9.5-specific probe revealed scant expression of PGP 9.5 in peripheral blood mononuclear cells, well below the limits of detection by electrophoresis alone. The system was able to detect a single neuroblastoma cell in 10(7) peripheral blood mononuclear cells. Eighteen patient samples were analyzed by PGP 9.5 RT-PCR and the results compared with immunocytology in 16. Ten of the 18 were negative by both studies. Eight of the 18 were positive by PGP 9.5 RT-PCR, 4 of which were also positive by immunocytology. PGP 9.5 RT-PCR was able to detect circulating neuroblasts in two patients with negative immunocytology, the first with progressive bone marrow disease and the second at high risk for relapse but no other evidence of disease. PGP 9.5 RT-PCR allows the detection of circulating neuroblastoma cells with a sensitivity greater than immunocytology. It will be useful in evaluating the clinical significance of circulating tumor cells with respect to prognosis and early detection of relapse, and in the screening of peripheral stem cell harvests prior to autologous infusion.
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PMID:Sensitive detection of rare circulating neuroblastoma cells by the reverse transcriptase-polymerase chain reaction. 138 Aug 88

A major question in the pathogenesis of AIDS encephalopathy and dementia is whether HIV-1 directly infects cells of the central nervous system (CNS). The propagation of HIV was attempted in six cell lines: three related and three unrelated to the nervous system. HIV was able to propagate in two human neuroblastoma cell lines and a lymphocytic cell line control but did not result in infections of African green monkey kidney cells, human cervix carcinoma cells, and one human brain astrocytoma cell line. Neuroblastoma cell lines infected with HIV showed peaks of reverse transcriptase activity at 10-14 days postinfection. After prolonged growth in cell cultures, one of the neuroblastoma cell lines showed multiphasic virus production, additional high peaks of reverse transcriptase activity, 20-fold greater than the first, lasting from 36 to 74 days and 110 to 140 days postinfection. The presence of HIV was confirmed by p24 antigen capture. The neuroblastoma cell lines had weak but detectable levels of CD4 immunoreactivity by immunoperoxidase and flow immunocytometric analysis. Although no T4-specific RNA sequences were detected by hybridization of Northern blots of total and poly A-selected RNA extracted from the two neuroblastoma cell lines by using a T4 specific complimentary DNA probe, monoclonal antibodies to the CD4 receptor blocked HIV infection in both neuroblastoma cell lines. Thus, the infection of neuroblastoma cells by HIV occurs in part by a CD4-dependent mechanism. Passaging the neuroblastoma cell lines weekly and bimonthly resulted in similar cell cycle-DNA content patterns for the more permissive cell line and with significant numbers of cells in the S phase. HIV-infected neuroblastoma cell lines provide an in vitro model for the evaluation of virus-host cell interactions and may be useful in addressing the issue of the persistence of HIV in the human CNS.
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PMID:HIV-1 propagates in human neuroblastoma cells. 170 60

Hybridization studies were carried out to measure sequence complexity and relative complexity of poly A-RNA populations from M1 neuroblastoma cells cultivated under proliferating conditions and after BrdU treatment. BrdU treatment is known to induce morphological differentiation. Hybridization kinetics were performed with [3H] labelled complementary DNA synthetized by reverse transcriptase action. The total complexities and the complexities of three classes of sequences measured for the two developmental states differed significantly. In particular, the total complexities as well as the complexity of the rare sequences class were higher in the poly A-RNA population of morphological differentiated M1 cells. Heterologous hybridization between poly A-RNA of proliferating cells with cDNA of differentiated M1 cells was very close to the homologous hybridization of poly A-RNA and cDNA from differentiated cells, nevertheless significant differences, were found in the intermediate and in the rare sequences classes. On the other hand the inverse heterologous hybridization (poly A-RNA of differentiated state X cDNA of proliferating cells) showed a lower hybridization in the region of Rot higher than 1. The plateau reached only 87 per cent compared to that of the homologous hybridization, suggesting that certain sequences expressed in the differentiated state. Nevertheless the number of different poly A-RNA species present per cell (seen by homologous hybridization experiments) was higher in differentiated state indicating that selective transcription took place beside repression with morphological differentiation.
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PMID:Hybridization studies of poly A-RNA from 5'-bromodeoxyuridine treated neuroblastoma cells. 615 27

The RET proto-oncogene, which encodes a receptor tyrosine kinase, displays multiple alternative splicing variants. Splicing of sequences 3' of exon 19 to generate several coding and untranslated region (UTR) sequences has been previously reported. We have sequenced the full length RET coding region and characterized the transcripts and 3' UTRs generated by alternative splicing of the RET 3' terminus. These analyses were performed using both RET cDNA cloned from a pheochromocytoma library and reverse transcriptase PCR products generated using RNA from a neuroblastoma cell line (LA-N-2). Three different carboxyl termini were identified. In addition to the nine and 51 terminal amino acid forms already known, we identified a third with 43 terminal amino acids predicted to encode a novel RET protein isoform. A total of 3621 base pairs of DNA 3' of exon 19, which spans the alternatively spliced exons and RET UTRs, was sequenced. Four polyadenylation sites were identified. The observed combinations of polyadenylation sites and 3' coding sequence suggest that RET transcripts with up to 10 different 3' sequences and up to 40 different full length RET transcripts may exist.
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PMID:Characterization of RET proto-oncogene 3' splicing variants and polyadenylation sites: a novel C-terminus for RET. 747 23

Expression of nitric oxide synthase (NOS) was studied in nine human neuroblastoma and two human glioblastoma cell lines. Neuronal NOS (n-NOS) mRNA of approximately 10 kb was detected in four of the nine neuroblastoma cell lines by northern blot analysis using human n-NOS cDNA as a probe. Expression of the n-NOS mRNA was also detected in another neuroblastoma cell line in a subsequent reverse transcriptase polymerase chain reaction (RT-PCR) study, but no n-NOS mRNA expression was observed in the other four neuroblastoma cell lines or in the glioblastoma cell lines. The level of NOS activity correlated well with that of n-NOS mRNA expression in neuroblastoma cell lines expressing n-NOS mRNA. Western blot analysis showed that the n-NOS expressed in neuroblastoma cells was a 160-kDa protein reacted with anti-n-NOS antibody. By using the RT-PCR method, a short n-NOS (n-NOS-2) mRNA with a 315-bp inframe deletion from the entire n-NOS (n-NOS-1) mRNA was detected in the human neuroblastoma cells. The structural diversity of human n-NOS mRNA was demonstrated for the first time.
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PMID:Expression of two types of nitric oxide synthase mRNA in human neuroblastoma cell lines. 751 42

Circulating cancer cells in the blood play a central role in the metastatic process. Their number can be very small and techniques for their detection need to be both sensitive and specific. Polymerase chain reaction (PCR) has been successfully used to detect small numbers of tumour cells in haematological cancer in which abnormalities in DNA are sufficiently consistent to make this possible. For most solid tumours this not yet feasible. However, we have found that reverse transcriptase (RT)-PRC for tissue-specific gene expression is a useful technique for identifying small numbers of circulating cells in melanoma and neuroblastoma patients. In this report we describe detection of colon carcinoma cells by RT-PCR using CK 20 mRNA as a marker. Unlike other cytokeratin genes examined (CK 8 and CK 19), CK 20 was not transcribed in normal haematopoietic cells. This suggests a role for RT-PCR in the detection of colon carcinoma metastasis in blood and bone marrow, using CK 20 as the target gene. Future analysis of clinical material will determine the clinical significance of this technique.
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PMID:Detection of epithelial cancer cells in peripheral blood by reverse transcriptase-polymerase chain reaction. 753 Sep 83

The 5-hydroxytryptamine3 receptor 5-HT3R has been implicated in gut and cardiac motility and in behavioral disorders. Characteristics of 5-HT3Rs appear to be heterogeneous among species, but human 5-HT3R cDNA has not been identified. We isolated a cDNA encoding 5-HT3R from human hippocampus. The mouse 5-HT3R gene has been reported to generate two alternative splicing isoforms that differ by six amino acids. All of our isolated human clones corresponded to the shorter isoform. Amino acid identities with mouse neuroblastoma N1E-115 and rat brain 5-HT3Rs were 84% for each. Southern blot analysis of human genomic DNA suggested that our cloned transcript encoded a human counterpart for the rodent 5-HT3Rs. This gene was assigned to chromosome 11 using polymerase chain reaction analysis of a human/rodent somatic cell hybrid panel. With the use of Northern blot analysis, 5-HT3R transcripts were identified in human small intestine, colon, and brain regions including hippocampus, amygdala, and striatum. In human heart, 5-HT3R expression was not detectable even with reverse transcriptase-polymerase chain reaction analysis, although it was detectable in mouse heart. Transfection of COS-1 with human 5-HT3R cDNA induced specific binding of the 5-HT3R-selective radioligand [3H]YM060. Human 5-HT3R showed typical characteristics of the 5-HT3R, but its affinity for the 5-HT3R agonist m-chlorophenylbiguanide was much lower than that of rat 5-HT3R. When injected with human 5-HT3R cRNA, the oocytes responded to 5-HT3R agonists with a rapidly developing inward current. The potency of the agonists to induce inward current paralleled that to compete with the radioligand binding, and 2-methyl-5-hydroxytryptamine, a partial agonist for mouse 5-HT3R, was a full agonist for human 5-HT3R. Our data revealed that the 5-HT3R molecule has interspecies differences in both tissue distribution and functional profile.
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PMID:Molecular cloning of human 5-hydroxytryptamine3 receptor: heterogeneity in distribution and function among species. 756 20

Calcyclin gene, a Ca(2+)-binding protein with homology to S-100, has been found to be expressed at different levels in leukaemic cells and in other tumour cells. We recently reported the expression of the gene in human neuroblastoma (NB) cell lines, and suggested a possible role of calcyclin in cell differentiation. To extend our findings, we investigated the expression of the gene in NB cells induced to differentiate by retinoic acid (RA), using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. Time-course experiments employing LA-N-5 cells showed that calcyclin mRNA appeared 2 h after RA treatment, long before the cells were blocked in the G1 cell-cycle phase and before the neurite-like structures outgrew from the cell bodies. This suggests the involvement of the gene in the early phase of cell differentiation. Furthermore, we investigated mRNA expression in a series of fresh neuroblastomas. NB tumours showed a heterogeneous pattern of calcyclin expression, although calcyclin seemed to be expressed more frequently in cases with a favourable Shimada histology. We also studied the expression of the protein in formalin fixed and paraffin embedded tissues, by using a specific anticalcyclin antibody. The protein was detected in stromal cells which characterise a more mature histological type, and in nerve sheaths, whereas neuroblasts were negative. The tissue that expressed calcyclin protein showed a Schwann-like differentiation and, unlike S-100 protein, calcyclin was expressed in the perineurium.
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PMID:Gene expression and protein localisation of calcyclin, a calcium-binding protein of the S-100 family in fresh neuroblastomas. 757 53


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