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)

Nervous system development involves a coordinated series of events, including regulation of cell proliferation and differentiation by specific extracellular factors. S100 beta is a neurotrophic protein that has been implicated in regulation of cellular proliferation, but direct evidence was lacking. In this report, nanomolar concentrations of S100 beta are shown to stimulate proliferation of rat C6 glioma cells and primary astrocytes. An S100 mutant with a single amino acid change was inactive. S100 beta also stimulated increases in the steady-state levels of c-myc and c-fos protooncogene mRNAs and complemented the effects of platelet-derived growth factor. Two neuroblastoma cell lines did not proliferate in response to S100 beta, suggesting that the mitogenic activity of S100 beta is selective for astroglial cells. These results suggest that S100 beta may be involved in the coordinate development and maintenance of the central nervous system by synchronously stimulating the differentiation of neurons and the proliferation of astroglia.
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PMID:Neurotrophic protein S100 beta stimulates glial cell proliferation. 190 67

In normal development the neural crest gives rise to sympathetic neuroblasts, sensory and autonomic ganglia, as well as Schwann cells. One tumor arising from this tissue is the neuroblastoma (NB), a malignancy of the adrenergic component of the sympathetic nervous system. Recent histological studies have shown that neuroblastomas can present with a schwannian cell component, rich in S100 protein. We have investigated the differentiation of NB cell lines, GOTO and RT-LN-1, into a schwannian cell phenotype using bromodeoxyuridine (BrdU). This agent induced morphological changes in these cell lines. Flat-epithelial cells were identified in the GOTO cell line and both flat-epithelial and neuronal phenotypes were found in the RT-LN-1 cell line. S100 protein (beta-Subunit) was induced in both cell lines after 18-25 days of BrdU treatment as determined by enzyme-linked immunoassay. In addition increase in the beta-subunit of S100 protein was identified in BrdU-treated flat-epithelial cells by indirect immunofluorescence using a monoclonal antibody specific for the beta-subunit of the protein. Cyclic nucleotide phosphodiesterase activity significantly increased in both BrdU-treated NB cell lines, as compared with nontreated cells. However no significant increase of glial fibrillary acidic protein in BrdU-treated cells was found either by enzyme-linked immunoassay or indirect immunofluorescence using a monoclonal antibody to glial fibrillary acidic protein. Thus, cells with Schwann cell characteristics can clearly be identified in the neuroblastoma cell lines after BrdU treatment. Fluorescence-activated cell sorting analysis revealed no quantitative changes in cell membrane antigens recognized by monoclonal antibodies UJ-13A (neuroectodermal associated antigen) and anti-Thy-1 (Thy-1) on BrdU treatment. In contrast, UJ-127-11 (neuroectodermal associated) decreased, and W6/32 and BB7.7 (HLA-ABC) and BBM.1 (beta 2-microglobulin) markedly increased in both BrdU-treated cell lines. No induction of L243 (HLA-DR), B7/21 (HLA-DP), and Genox 3.55 (HLA-DQ) was noted. The increased HLA-ABC (HLA class I) antigen may enable BrdU-treated NB cells to be recognized by cytotoxic T-cells. This may be related to the pathological evidence that NB patients whose tumors are rich in S100 protein have a better prognosis. Further studies on the potential of differentiation agents to induce a phenotypic change, that is associated with an improved prognosis for NB patients, are required.
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PMID:Schwannian cell differentiation of human neuroblastoma cell lines in vitro induced by bromodeoxyuridine. 283 49

Forty-one confirmed cases of childhood neuroblastoma diagnosed over a 13-year period were reviewed and reclassified. Most of the tumors were stained using a peroxidase antiperoxidase method for neuron specific enolase (NSE), protein gene product (PGP) 9.5, and S100 protein, all of which have previously been reported to be positive in some neuroblastomas. The relation to prognosis of the histology and immunohistochemistry was studied. There was a significant trend toward improved survival with increasing degree of differentiation, and with decreasing mitosiskaryorrhexis index (MKI) in the stroma-poor group. There was no significant correlation between immunohistochemical staining and survival, although the presence and amount of staining for all three markers tended to increase with tumor differentiation. This study concludes that histologic classification in neuroblastoma is helpful in assessing prognosis but that the clinical features are generally more reliable as indicators of prognosis. The immunohistochemistry of markers used did not contribute towards assessment of prognosis.
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PMID:Histologic and immunohistochemical investigation of neuroblastomas and correlation with prognosis. 296 64

The efficacy of two new monoclonal antibodies with cell lineage-restricted reactivity (HMB-45 [melanocytes] and anti-synaptophysin [neuroepithelial cells]) was compared with that of "traditional" antibody panels in the delineation of malignant melanoma (MM) of the sinonasal region, nasopharyngeal carcinoma (NPC), and olfactory neuroblastoma (ONBL). HMB-45 recognized all of eight melanomas and stained one of five neuroblastomas, but failed to label any of 12 cases of NPC. All examples of ONBL were stained by anti-synaptophysin; other tumors were nonreactive with this reagent. A panel of antibodies to cytokeratin, vimentin, epithelial membrane antigen, and S100 protein was also effective in discriminating between MM, NPC and ONBL. These results suggest that HMB-45 and anti-synaptophysin are comparable in utility to more extended antibody panels in the diagnosis of sinonasal malignancies, but only if used in combination with one another.
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PMID:Immunohistochemical diagnosis of sinonasal melanoma, carcinoma, and neuroblastoma with monoclonal antibodies HMB-45 and anti-synaptophysin. 337 60

The intratumorous distribution of catecholaminergic tumour cells and S100 protein-positive elements of 8 neuroblastomas, 8 ganglioneuroblastomas and 2 ganglioneuromas were studied using catecholamine fluorescence and immunohistochemical staining, respectively. The elements of catecholamine fluorescence were observed in all tumour specimens, even in urinary VMA-negative cases, but the patterns of distribution were not uniform. Catecholamine fluorescence was observed in both tumour cell bodies and neurofibres, and the appearance of the latter but not that of the former correlated with the histological grade of differentiation, thereby suggesting the occurrence of catecholaminergic differentiation within the tumour. S100 protein-positive elements also correlated with the histological differentiation, and were distributed mostly in the area where the catecholamine-containing neurofibres were located. The possible correlation between catecholaminergic differentiation and the appearance of S100 protein-positive elements in neuroblastoma requires close attention.
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PMID:Catecholaminergic differentiation associated with S100 protein-positive elements in human neuroblastoma. 353 92

Melanotic neuroectodermal tumors of infancy (MNTI) are uncommon, usually benign neoplasms, most frequently found in the maxilla. These tumors are extremely rare in the epididymis. Only 18 cases with this site of origin are documented. We report on the third epididymal MNTI with some morphological characteristics of malignancy but favorable clinical outcome. The 2 cm large tumor of a 6-month-old male infant showed large epitheloid cells in the center and small neuroblastoma-like cells at the periphery. Despite invasion of lymphatics there is no evidence of relapse or metastases during 4 years of follow-up. Immunohistochemically, the large tumor cells were distinctly positive for cytokeratin, vimentin, GFAP, the melanoma marker NKI-C3, NSE, and S100. The small tumor cells were only slightly positive for GFAP, NKI-C3, NSE, and S100 but they were negative for cytokeratin and vimentin. Neurofilament and chromogranin could not be proved in the tumor.
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PMID:Melanotic neuroectodermal tumor of infancy (MNTI) in the epididymis. A case report with immunohistological studies and special consideration of malignant features. 794 25

Immunohistochemical analysis of five paraffin wax-embedded neoplasms was performed to elucidate the characteristics of bovine nervous-tissue tumours. In case 1 (peripheral neuroblastoma), the neoplastic tissue was characterized by the formation of true and Homer-Wright rosettes and the existence of neuron-specific enolase. The neoplastic cells were possibly more immature than those of common neuroblastomas, because similar features are observed in human malignant neuroepitheliomas. The neoplastic cells in case 2 (ganglioneuroblastoma) ranged from large cells with abundant neurofilaments to immature small cells, rarely with neurofilaments or glial fibrillary acidic protein (GFAP). Such expression suggests the presence of pluripotential cells. The neoplastic tissue in case 3 (anaplastic ganglioglioma) was strikingly polymorphous, and had five elements; neuronal, astrocytic, oligodendrocytic, spindle cell and small oval cell. The neoplastic neurocytes and astrocytes were, respectively, characterized by neurofilament and GFAP positivity. The neoplastic oligodendrocytes made a honeycomb appearance, and the neoplastic spindle cells and small oval cells were considered to be less differentiated. The tumours of cases 2 and 3, which contained poorly differentiated cells and revealed both neuronal and glial differentiation, may be specific to calves. In case 4 (schwannoma), almost all the neoplastic cells were positive for S100 protein, while S100-negative fibroblasts were present in many areas of case 5 (neurofibroma). These two tumours were readily distinguished histologically and immunohistochemically.
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PMID:An immunohistochemical study of peripheral neuroblastoma, ganglioneuroblastoma, anaplastic ganglioglioma, schwannoma and neurofibroma in cattle. 796 22

To determine if immunohistochemistry might aid in the identification of neuroblastomatous foci in composite adrenal tumors, the authors analyzed two examples of composite adrenal pheochromocytoma-neuroblastoma, 18 pure pheochromocytomas, and six pure neuroblastomas using peanut agglutinin and a panel of antibodies directed against neuroendocrine and neural-associated antigens. Pure pheochromocytoma had the following immunopositivity: vimentin 14/18, chromogranin 18/18, synaptophysin 18/18, S100 protein 0/18 (tumor cells), neurofilament 14/18, J1 beta-tubulin (J1) 18/18, microtubule-associated protein-2 13/18, glial fibrillary acidic protein 13/18, and peanut agglutinin 17/18. Pure neuroblastoma reacted positively as follows: vimentin 0/6, chromogranin 5/6, synaptophysin 4/6, S100 protein 0/6 (tumor cells), neurofilament 5/6, J1 6/6, microtubule-associated protein-2 6/6, glial fibrillary acidic protein 1/6, and peanut agglutinin 6/6. Each component of both composite tumors reacted similarly to the pure neoplasms. Although the frequency of positive staining was similar for pheochromocytoma and neuroblastoma, the intensity and pattern differed for several antigens. Pheochromocytoma was diffusely positive for synaptophysin and chromogranin, whereas staining was focal and punctate in neuroblastoma. Microtubule-associated protein-2, J1, and neurofilament antibodies highlighted the fibrillar background of neuroblastoma, which pheochromocytoma lacked. Pheochromocytoma contained focal, ball-like immunoreactivity for glial fibrillary acidic protein and vimentin, which was absent in neuroblastoma. These immunohistochemical distinctions can assist the clinically important recognition of neuroblastomatous foci in composite adrenal pheochromocytoma-neuroblastoma.
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PMID:Immunohistochemical detection of neuroblastomatous foci in composite adrenal pheochromocytoma-neuroblastoma. 804 83

Two patients, 14 and 46 years of age, presented with diffuse, rapidly growing intracerebral tumors leading to death 6 1/2 and 9 1/2 months, respectively, after diagnosis. Histological examination showed sheets of moderate-sized tumor cells with clear cytoplasm and central nuclei interrupted by delicate arciform vasculature, an appearance distinctly different from that of neuroblastoma. Malignant features were present in the form of significant nuclear pleomorphism, numerous mitotic figures, and small foci of necrosis with some suggestion of adjacent pseudo-palisading in one case. Ultrastructural examination showed neuronal differentiation, including prominent neuritic processes, microtubules, dense-core neurosecretory-type granules, and synaptic bouton-like structures containing small, empty-appearing synaptic-type vesicles and synapse-like membrane "thickenings." Immunohistochemistry showed focal immunopositivity for synaptophysin, neurofilaments, neuron-specific enolase, and S100 protein. Immunoreactivity for glial fibrillary acidic protein (GFAP) was found at the margins of the tumors adjacent to some intratumoral blood vessels and in some tumor cells. These tumors seem to occupy a nosological "middle ground" between neuroblastoma and central neurocytoma.
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PMID:Malignant neurocytic tumor. 805 20

The sensitive and specific biochemical indicators for assessing chemical-induced neurotoxic insults in cell culture models have not been sufficiently explored. This study was designed to assess the usefulness of glia-specific beta-S100 protein and neuron-specific enolase (NSE) as indices of in vitro neurotoxicity of heavy metals. Glioma C6 and neuroblastoma N18TG-2 cells were grown in Dulbecco's modified Eagle's medium containing various concentrations of mercuric chloride (HgCl2) or cadmium chloride (CdCl2) for 5 days. Toxic response patterns of the neurospecific endpoints (beta-S100 and NSE), which were monitored with enzyme immunoassays, were compared with those of the non-neurospecific endpoints such as cell viability, total cellular protein, lactate dehydrogenase (LDH) activity, and cumulative glucose consumption in the two cell lines. Both HgCl2 and CdCl2 produced dose-dependent inhibition of neurospecific endpoints and non-specific endpoints. However, by ranking the EC50 values (effective concentration producing half-maximal inhibition) for various endpoints, the lowest values were found for beta-S100 in C6 cells, and for NSE in N18TG-2 cells. In lower and intermediate concentrations, the inhibitory effects of the heavy metals on the content of beta-S100 and NSE occurred in the absence of any detectable effect on intracellular LDH activity, and independently of total cellular protein inhibition. The sensitive and excess responses of the neurospecific endpoints relative to that of the non-specific endpoints may reflect the specific neurotoxic insults of the heavy metals on the cultured cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuron and glial cell marker proteins as indicators of heavy metal-induced neurotoxicity in neuroblastoma and glioma cell lines. 823 98


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