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)

Transgenic mice carrying a cDNA to the polyoma virus middle T (mT) antigen linked to the thymidine kinase promoter were generated to study the consequences of deregulated expression of mT-associated tyrosine kinase activity in a wide variety of tissues. Four independent transgenic founder animals were obtained, from one of which was established a transgenic line. This mouse and all its offspring developed multiple neuroblastomas between 2 and 3 months of age. Expression of the transgene (assayed by tyrosine kinase assay and in situ hybridization) was restricted to the neurons of the central and peripheral nervous tissue, probably because of a positional effect of the transgene integration. Characteristic preneoplastic lesions in the sympathetic ganglia and in the adrenal medulla were identified from which the neuroblastomas originated. The tumors arising in these mice show striking analogies to human neuroblastomas, including the sites of development of the tumors, their histological and ultrastructural appearance, and the expression of diagnostic markers, such as synaptophysin, and high expression of the N-myc oncogene. This animal model thus provides a unique tool for studying growth control in sympathetic neuroblasts and the pathogenesis of neuroblastoma.
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PMID:Sympathetic hyperplasia and neuroblastomas in transgenic mice expressing polyoma middle T antigen. 208 3

A continuous tumor cell line (LAP-35) was established from a primitive neuroectodermal tumor of bone from the right tibia of a 12-year-old female. The neural character of the cell line was documented by the spontaneous growth of neurites and by the presence of several neural markers, including neuron-specific enolase (NSE), S-100 protein, neurofilaments, chromogranin A, synaptophysin and positivity to monoclonal antibodies UJ127.11, UJ13A, UJ181.4. Cell-sorter analysis showed a high expression of nerve growth factor receptor (NGFr) and major histocompatibility complex class I-related molecules. A unique cytogenetic profile was observed, including a reciprocal chromosomal translocation (rct) 11:22 (q24;q12), typically associated with Ewing's sarcoma and neuroepithelioma, and deletion of the short arm of chromosome 1 (lp-), otherwise a feature of neuroblastoma. N-myc proto-oncogene was neither amplified nor expressed, whereas the expression of c-myc was documented by northern blot analysis. These features distinguish this new cell line from previously reported neuroectodermal cell lines, identifying LAP-35 as a unique model of a group of neural bone tumors that share characteristics of neuroblastoma as well as neuroepithelioma.
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PMID:Establishment and characterization of a primitive neuroectodermal tumor of bone continuous cell line (LAP-35). 217 80

Human neuroblastoma cells were cultured either in the absence or presence of 12-O-tetradecanoylphorbol-13-acetate (TPA) known to induce neuronal differentiation. This treatment led to a marked increase in the concentration of secretogranin II but to a decrease of chromogranin A. Analogous changes were observed for the respective mRNAs. Thus during differentiation of these cells the biosynthesis of two vesicle constituents of large dense core vesicles is differentially regulated as determined both at the mRNA and the protein level. Levels of both synaptin/synaptophysin large dense core vesicles is differentially regulated as determined both at the mRNA and the protein level. Levels of both synaptin/synaptophysin and SV2 were also elevated but to a smaller degree than that of secretogranin II.
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PMID:Divergent changes of chromogranin A/secretogranin II levels in differentiating human neuroblastoma cells. 236 53

IMR-32 human neuroblastoma cells are unable to release [3H]dopamine in response to secretagogues. However, they express a normal complement of membrane receptors and ion channels which are efficiently coupled to second messenger production. In the present study we took advantage of the ability of this cell line to differentiate in vitro in the presence of either dibutyrryl-cAMP or 5-bromodeoxyuridine, to analyze any developmentally regulated changes in its secretory properties. Uptake, storage, and release of [3H]dopamine were studied biochemically and by autoradiography. The calcium ionophore ionomycin, phorbol 12-myristate 13-acetate and the presynaptic acting neurotoxin alpha-latrotoxin were used in both control and differentiated cells as secretagogue agents. The presence of secretory organelles was investigated by electron microscopy; the expression of secretory organelle markers, such as chromogranin/secretogranin proteins (secretory proteins) and synaptophysin (membrane protein), was detected by Western blotting and immunofluorescence. The results obtained indicate that IMR-32 cells acquire regulated secretory properties after in vitro drug-induced differentiation: (a) they assemble "de novo" secretory organelles, as revealed by electron microscopy and detection of secretory organelle markers, and (b) they are able to store [3H]dopamine and to release the neurotransmitter in response to secretagogue stimuli. Furthermore, secretagogue sensitivity was found to be different, depending on the differentiating agent. In fact, dibutyrryl-cAMP treated cells release [3H]dopamine in response to alpha-latrotoxin, but not in response to ionomycin, whereas 5-bromodeoxyuridine treated cells release the neurotransmitter in response to both secretagogues. All together these results suggest that IMR-32 cells represent an adequate model for studying the development of the secretory apparatus in cultured human neurons.
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PMID:Human neuroblastoma cells acquire regulated secretory properties and different sensitivity to Ca2+ and alpha-latrotoxin after exposure to differentiating agents. 254 6

Renal tumors of childhood occasionally exhibit histopathologic and clinical features that preclude accurate diagnosis. Molecular and cell culture techniques may be helpful in better characterizing these cases. This approach was used to examine unusual bilateral renal tumors from a young boy. The left kidney tumor was an undifferentiated neoplasm with light microscopic features suggestive of both Wilms' tumor and neuroblastoma, and the right kidney tumor was identified as multilocular cystic nephroma (MLCN). In vitro tissue culture of tumor cells and hybridization experiments with an N-myc oncogene DNA probe contributed to a revised diagnosis of intrarenal neuroblastoma of the left kidney. A cell line established from the left tumor exhibited neurite outgrowth and was positive for neuron-specific enolase and synaptophysin. N-myc was greater than ten-fold amplified in chromosomal DNA from the left kidney tumor. Measurement of N-myc RNA expression enabled distinction between benign and malignant tumor tissue. The detection of N-myc gene amplification predicted a poor prognosis which was confirmed by the patient's subsequent clinical course.
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PMID:N-myc oncogene expression in histopathologically unrelated bilateral pediatric renal tumors. 283 41

Synaptophysin, an integral membrane glycoprotein of presynaptic vesicles, was tested as an immuno-histochemical marker for childhood neuroblastoma. Synaptophysin immuno-reactivity was found in all neuroblastomas (6/6), but not in the other small round-cell tumors to be considered in its differential diagnosis. Thus, rhabdomyosarcomas (0/5), lymphomas (0/4), or Ewing's sarcomas (0/2) were negative for synaptophysin. The results suggest that synaptophysin is a useful marker for neuroblastoma, and it should belong to the marker panel used for the differential diagnosis of small round-cell tumors of childhood.
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PMID:Synaptophysin--an immuno-histochemical marker for childhood neuroblastoma. 311 75

Synaptophysin, an Mr 38,000 integral membrane glycoprotein of neurotransmitter vesicles, has been identified in diverse primary neuroendocrine (NE) tumors of both neural and epithelial origin (Wiedenmann and co-workers, Proc Natl Acad Sci USA 1986; 83: 3500-3504). In the present study, metastases of several types of NE tumors, including medullary thyroid carcinoma, gastrinoma, insulinoma, small (oat) cell carcinoma of the lung, gastrointestinal carcinoid, and neuroblastoma, were examined for the presence of synaptophysin by immunocytochemistry, with the use of tissue sections as well as centrifuged cell suspensions and by immunoblotting of tumor proteins. The results show that expression of synaptophysin can be maintained during formation of metastases. Therefore, the authors propose that synaptophysin antibodies be used for the positive identification of metastatic NE tumors, notably in differential diagnosis. The possible implications of these findings for tumor diagnosis are discussed.
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PMID:Synaptophysin identified in metastases of neuroendocrine tumors by immunocytochemistry and immunoblotting. 311 96

A continuous cell line was established from an explanted tumor biopsy obtained from a patient with advanced neuroblastoma, which showed no response to chemotherapy. This cell line MHH-NB-11 retained most properties of the original immature tumor, even after xenotransplantation into nude mice. The cell line consisted of small dense cells with scant cytoplasm and thin; long processes and expressed neuron-specific enolase and synaptophysin, but neither GFAP nor S-100 protein. Karyotyping showed karyograms with 49 to 54 chromosomes, with a modal at 52. Most cells had trisomy 2,7,8,20, but only few structural aberrations were observed. Two of four chromosomes 1 showed a rearrangement of the terminal 1p segment, and all cells had a long HSR on the long arm of one of the chromosomes 13. This region hybridized in situ with the N-myc probe pNB-1. N-myc was amplified 20-fold in this neuroblastoma cell line as determined in Southern blot analysis. This cell line should be a useful tool in vitro or as a xenograft model for neuroblastoma research.
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PMID:Characterization of a continuous cell line (MHH-NB-11) derived from advanced neuroblastoma. 321 65

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

A 7-cm anterior mediastinal tumor in an 80-year-old woman was found by light and electron microscopy to be a neuroblastoma. Immunoreactivity for neuron-specific enolase, synaptophysin, and chromogranin supported the diagnosis. Neuroblastoma is an uncommon tumor in adults and we are not aware of a previous report of such a tumor in a patient of this age.
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PMID:Neuroblastoma of the anterior mediastinum in an 80-year-old woman. 757 Oct 89


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