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)

Phosphatidylinositol (PI) breakdown represents a powerful system participating in the transduction mechanism of some neurotransmitters and growth factors and producing two second messengers, diacylglycerol and inositol trisphosphate. The transformation of PC12 neuroblastoma cells into neuron-like cells induced by nerve growth factor (NGF) is preceded by a rapid stimulation of PI breakdown; however, it was not known whether PI breakdown mediates actions of other members of the neurotrophin family. The present study analyzed the effects of NGF, brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) on PI breakdown in primary cultures of embryonic rat brain cells. Cultures were grown for 7 days; PI was then labeled by incubating cultures with myo-[3H]inositol, which then were exposed acutely to growth factors. BDNF and NT-3, but not NGF, elevated the levels of labeled inositol phosphates within 10-15 min after addition to the cultures in a dose-dependent manner. ED50 values for BDNF and NT-3 were 12.4 and 64.5 ng/ml, respectively. Comparable effects were found in cultures of cortical, striatal, and septal cells. The actions of BDNF and NT-3 probably reflect actions on neurons, because no effects were seen in cultures of nonneuronal cells. In contrast, basic fibroblast growth factor induced a marked stimulation of PI breakdown in cultures of nonneuronal cells. K252b, which selectively blocks neurotrophin actions by inhibiting trk-type receptor proteins, prevented the PI breakdown mediated by BDNF and NT-3. The findings suggest that rapid and specific induction of PI breakdown is involved in the signal transduction of BDNF and NT-3, and they provide evidence that cortical neurons are functionally responsive to BDNF and NT-3 during development.
J Neurochem 1992 Dec
PMID:Stimulation of phosphatidylinositol hydrolysis by brain-derived neurotrophic factor and neurotrophin-3 in rat cerebral cortical neurons developing in culture. 143 96

Cellular differentiation is often associated with striking changes in ganglioside metabolism. Because retinoic acid causes cellular differentiation in vitro, we have characterized its effect on ganglioside synthesis and shedding by LAN-5 human neuroblastoma cells. Three major observations were made: (a) 20 microM retinoic acid caused a marked (twofold) increase in cellular ganglioside content, with a slight relative enhancement in GD1a and GT1b synthesis, (b) ganglioside shedding increased in parallel with increased cellular ganglioside content, and also, unexpectedly, (c) retinoic acid caused a quantitatively similar increase in content of cell membrane phospholipids, which are also shed. We conclude that enhanced ganglioside synthesis and shedding by retinoic acid are part of a previously undescribed generalized stimulatory effect on membrane lipid metabolism.
J Neurochem 1992 Dec
PMID:Alteration of neuroblastoma ganglioside metabolism by retinoic acid. 143 8

Oncogene amplification is observed frequently in human cancers, but little is known about the mechanism of gene amplification or the structure of amplified DNA in tumor cells. We have studied the N-myc amplified domain from a representative neuroblastoma cell line, SMS-KAN, and compared the map of the amplicon in this cell line with that seen in normal DNA. The SMS-KAN cell line DNA was cloned into yeast artificial chromosomes (YACs), and clones were identified by screening the YAC library with amplified DNA probes that were obtained previously (B. Zehnbauer, D. Small, G. M. Brodeur, R. Seeger, and B. Vogelstein, Mol. Cell. Biol. 8:522-530, 1988). In addition, YAC clones corresponding to the normal N-myc locus on chromosome 2 were obtained by screening two normal human YAC libraries with these probes, and the restriction maps of the two sets of overlapping YACs were compared. Our results suggest that the amplified domain in this cell line is a approximately 1.2-Mb circular molecule with a head-to-tail configuration, and the physical map of the normal N-myc locus generally is conserved in the amplicon. These results provide a physical map of the amplified domain of a neuroblastoma cell line that has de novo amplification of an oncogene. The head-to-tail organization, the general conservation of the normal physical map in the amplicon, and the extrachromosomal location of the amplified DNA are most consistent with the episome formation-plus-segregation mechanism of gene amplification in these tumors.
Mol Cell Biol 1992 Dec
PMID:Isolation and structural analysis of a 1.2-megabase N-myc amplicon from a human neuroblastoma. 144 86

Neuroblastoma is the third most common type of cancer seen in children, after leukemia and tumours of the central nervous system. Although bony metastasis to the skull and the orbits has been well described, metastasis to the mandible is exceptional; 32 cases have been reported. Two more are presented here, along with a short review of the topic emphasizing the radiographic features and the differential diagnosis.
Can Assoc Radiol J 1992 Dec
PMID:Metastatic neuroblastoma presenting as a mandibular mass. 145 Sep 73

The authors report a case of subcutaneous nodules in a 2-month-old girl with metastatic neuroblastoma; the appearance of the nodules in computed tomography scans is described. Such nodules are sometimes overlooked by clinicians and radiologists, even though they almost always occur in disseminated disease. In patients with neuroblastoma and other neoplasms subcutaneous nodules may be an easily accessible source of samples for histopathologic examination.
Can Assoc Radiol J 1992 Dec
PMID:The computed tomographic appearance of subcutaneous nodules occurring in metastatic neuroblastoma. 145 Sep 74

Na(+)-dependent amino isobutyric acid transport by two neuroblastoma cell lines with and without amplification of the oncogene N-myc is studied. Surprisingly, the contribution of system A is greater in the cell line showing no N-myc amplification. Preliminary data support a role for essential tyrosine and cysteine residues in the active center of the carriers, mainly in system A.
FEBS Lett 1992 Dec 07
PMID:Na(+)-dependent AIB transport by neuroblastoma cells. 145 99

Neurofibromatosis type 1 (NF1) is caused by mutations in a large gene on chromosome 17q11.2. Previously described partial cDNAs for this gene predicted a protein related to yeast IRA1/IRA2 and the mammalian RAS GTPase activator protein GAP. To initiate a detailed study of the role of this gene in NF1, we have characterized a set of overlapping cDNAs that represent its complete coding sequence. Our results show that two differentially expressed human NF1 mRNAs differ by a 63-bp insertion in the GAP-related domain. These mRNAs predict two 2,818- and 2,839-amino acid proteins with calculated molecular masses of approximately 317 and 319 kD. Extensive similarity to IRA proteins is evident in a 1,450-amino-acid central segment, roughly between amino acids 900 and 2,350. However, the remainder of the NF1 protein is not significantly similar to other proteins. Interestingly, the SK-N-SH human neuroblastoma line expresses no detectable NF1 mRNA, indicating that expression of NF1 is not essential for viability of this neural crest-derived tumor cell line.
DNA Cell Biol 1992 Dec
PMID:Complete human NF1 cDNA sequence: two alternatively spliced mRNAs and absence of expression in a neuroblastoma line. 145 41

Mathematical models have predicted that targeted radiotherapy of neuroblastoma with metaiodobenzylguanidine (mIBG) is less likely to cure small rather than large micrometastases if 131I is the conjugated radionuclide. This study uses multicellular tumour spheroids as an in vitro model to test the hypothesis that smaller tumours of sub-millimetre dimensions are relatively resistant to 131I-mIBG. Spheroids of the human neuroblastoma cell line SK-N-BE(2c), either 250 microns or 400 microns diameter, were incubated with 131I-mIBG at concentrations of up to 6.0 MBq ml-1. Using both regrowth delay and spheroid 'cure' as endpoints, the greater vulnerability of larger spheroids was confirmed. From this in vitro result we conclude that when used in vivo 131I-mIBG may spare smaller micrometastases. Therefore, either a radionuclide such as 211At which emits a shorter path length radiation should be conjugated to mIBG, or targeted radiotherapy should be combined with a treatment such as total body irradiation, the efficacy of which is not reduced in smaller tumours.
Br J Cancer 1992 Dec
PMID:131I-meta-iodobenzylguanidine therapy in neuroblastoma spheroids of different sizes. 145 44

Human immunodeficiency virus (HIV) infection of brain macrophages and astroglial proliferation are central features of HIV-induced central nervous system (CNS) disorders. These observations suggest that glial cellular interactions participate in disease. In an experimental system to examine this process, we found that cocultures of HIV-infected monocytes and astroglia release high levels of cytokines and arachidonate metabolites leading to neuronotoxicity. HIV-1ADA-infected monocytes cocultured with human glia (astrocytoma, neuroglia, and primary human astrocytes) synthesized tumor necrosis factor (TNF-alpha) and interleukin 1 beta (IL-1 beta) as assayed by coupled reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and biological activity. The cytokine induction was selective, cell specific, and associated with induction of arachidonic acid metabolites. TNF-beta, IL-1 alpha, IL-6, interferon alpha (IFN-alpha), and IFN-gamma were not produced. Leukotriene B4, leukotriene D4, lipoxin A4, and platelet-activating factor were detected in large amounts after high-performance liquid chromatography separation and correlated with cytokine activity. Specific inhibitors of the arachidonic cascade markedly diminished the cytokine response suggesting regulatory relationships between these factors. Cocultures of HIV-infected monocytes and neuroblastoma or endothelial cells, or HIV-infected monocyte fluids, sucrose gradient-concentrated viral particles, and paraformaldehyde-fixed or freeze-thawed HIV-infected monocytes placed onto astroglia failed to induce cytokines and neuronotoxins. This demonstrated that viable monocyte-astroglia interactions were required for the cell reactions. The addition of actinomycin D or cycloheximide to the HIV-infected monocytes before coculture reduced, > 2.5-fold, the levels of TNF-alpha. These results, taken together, suggest that the neuronotoxicity associated with HIV central nervous system disorders is mediated, in part, through cytokines and arachidonic acid metabolites, produced during cell-to-cell interactions between HIV-infected brain macrophages and astrocytes.
J Exp Med 1992 Dec 01
PMID:Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease. 146 Apr 27

A 65-year-old man with lower back pain was found to have multiple myeloma. Unique findings in the marrow aspirate smears of this patient were tadpolelike plasma cells and cellular rosettes simulating those seen in neuroblastoma. This case documents yet another facet of the broad morphologic spectrum of neoplastic plasma cells in multiple myeloma.
Am J Clin Pathol 1992 Dec
PMID:Multiple myeloma with tadpolelike cells and rosette formation. 146 60


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