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)

We examined 52 children with advanced neuroblastoma who were diagnosed and treated during the past 7 years, and investigated the correlation between the degree of lymph node (LN) metastasis and the prognosis of neuroblastoma. In 8 of the 52 patients, distant LN metastasis was confirmed both radiographically and histologically. The urinary homovanillic acid (HVA) level was markedly elevated in these patients, and it was higher than that in patients with regional LN metastasis (p less than .05). The urinary vanillylmandelic acid (VMA) level and the VMA/HVA ratio were not significantly different between patients with regional and distant LN metastasis. None of the four examined patients with distant LN metastasis showed N-myc amplification of neuroblastoma tumors. An analysis of the survival rate in each patient group classified according to the degree of LN metastasis showed that the prognosis of the patients without LN metastasis or with distant LN metastasis tended to be better than that of patients with regional LN metastasis. Our results indicate that patients with distant LN metastasis may belong to a subclass with different biological features and a better prognosis than those of other groups.
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PMID:Features and outcome of advanced neuroblastoma with distant lymph node metastasis. 155 70

A new mouse monoclonal antibody specific for N-myc oncoprotein was generated and used in combination with an anti-c-myc antibody to develop two color immunofluorescence staining and ultrastructural immunolocalization of N-myc and c-myc in well established (SK-N-SH; CHP 126) and in newly established neuroblastoma (NB) cell lines. Analysis and quantitation of c-myc and N-myc in dually stained cells was done by flow cytometry. Immunolocalization was done by staining with immunogold secondary antibodies and transmission electron microscopy. The results obtained from analysis of 13 newly established NB cell lines revealed, great heterogeneity in the expression of N-myc oncoprotein with 10/13 cell lines over expressing the protein. C-myc oncoprotein was also expressed in all cell lines, however, the level of expression was 4-10-fold lower than the N-myc oncoprotein. Localization studies of c-myc and N-myc oncoproteins on the level of light microscopy and electron microscopy revealed exclusive nuclear localization of c-myc whereas N-myc was localized to the nucleus and to the cytoplasm.
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PMID:Development of a two color immunofluorescence stain and immunolocalization method for N-myc and c-myc oncoproteins with a newly generated mouse IgM anti N-myc antibody. 156 26

Expression of the N-myc oncogene is an important determinant of tumor behavior in human neuroblastoma. To study the regulation of N-myc, we have subcloned fragments of the 5' flanking region of the human N-myc gene upstream of the chloramphenicol acetyl transferase (CAT) reporter gene, and assayed for promoter activity in transient transfections into neuroblastoma and other cell lines. Upstream sequences were found to possess promoter activity to within 121 bp of the major cap site (-121). Negative regulatory elements were identified in regions approximately 2 kb and 500 bp upstream from the major cap site, as well as 150-1000 bp downstream. Promoter constructs containing downstream elements from bp +150 to +1000 were active in N-myc-expressing neuroblastoma cell lines, but not in non-expressing Epstein-Barr virus (EBV)-transformed 729-6 B-cell or HeLa cell lines, while those lacking this element were active in all cell types tested. All tested constructs retaining promoter activity showed decreased activity in parallel with the down-regulation of endogenous N-myc in response to treatment of transfected cells with retinoic acid. These studies suggest that N-myc regulation may be controlled at different levels, and provide a basis for further characterization of N-myc regulation in neuroblastoma.
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PMID:Cell type-specific expression and negative regulation by retinoic acid of the human N-myc promoter in neuroblastoma cells. 156 67

Human neuroblastoma cells often carry cytogenetic abnormalities signaling amplification of the gene N-myc. In most cell lines amplified N-myc is localized in homogeneously staining regions (HSRs). Varying proportions of the amplified DNA consist of multiple tandem arrays of DNA segments encompassing N-myc. Here we report the cloning and sequencing of a DNA breakpoint which represents the joint of the tandem repeats of a 280-kb amplicon of neuroblastoma line NMB. The breakpoint is located in the first intron of the N-myc gene and leads to the deletion of the 5' region of N-myc in this 20-copy amplicon. The representation of DNA derived from the non-N-myc part of the novel joint in the different amplicons suggests that an increase in N-myc copy numbers involves a multistep process proceeding from large 'precursors' to smaller multicopy amplicons.
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PMID:Multiple amplicons of discrete sizes encompassing N-myc in neuroblastoma cells evolve through differential recombination from a large precursor DNA. 156 78

Twenty-nine previously untreated neuroblastomas were analyzed for DNA content and percentage of cells in S-phase, both determined by flow cytometry, and N-myc oncogene copy number. Twelve of them were also tested for histone H3 transcript levels as a marker of actual proliferative activity. A significantly higher S-phase fraction was associated with advanced stages of disease, unfavorable (i.e., near-diploid and near-tetraploid) DNA content, and N-myc amplification. The occurrence of six tumors with a remarkable (greater than or equal to 10%) S-phase fraction but lacking histone H3 transcripts suggests the presence of stationary S-phase cells in neuroblastoma.
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PMID:Flow cytometric and molecular analysis of proliferative activity and DNA content in neuroblastoma: presence of stationary cells in S-phase. 156 82

N-myc expression has been reported in neuroblastoma, retinoblastoma and small cell lung carcinoma. Increased expression associated with gene amplification in neuroblastoma correlates with disease stage and prognosis. N-myc expression has been observed in diverse murine tissues during early stages of development with loss of expression in later stages. Abelson murine leukemia virus (A-MuLV)-transformed pre-B cells express N-myc, whereas mature B cells do not. To determine whether human B-lymphocyte precursors also have increased N-myc expression, we extracted DNA and RNA from representative cell lines, prepared Southern and Northern blots and examined them with the N-myc probe, pNB-1. RNA from the following B-cell developmental stages were examined. One null, 1 pre-pre-B, 3 pre-B (including pre-B-lymphoblastic leukemia, a poor prognostic category) and 5 mature B. Neuroblastoma cells and tissues served as positive controls; negative controls included human muscle, placenta, epithelial cell lines, monocytic, promyelocytic, and T-cell lines. N-myc expression was detected in neuroblastoma cells, but in none of the mature human B or B-lymphocyte precursor cells. Additional immunocytochemical studies performed for N-myc nuclear protein likewise failed to detect this gene product. We conclude that human pre-B cells, unlike murine B-cell precursors, do not express increased levels of N-myc RNA. Expression of this oncogene in human neoplastic B cells does not appear to correlate with developmental stage or prognostic group.
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PMID:Human B-lymphocyte precursors do not express the N-myc gene. 157 Oct 96

N-myc gene amplification was studied in a consecutive series of neuroblastomas and ganglioneuromas, representing all of such tumours diagnosed in Sweden over a 4-year period. Both frozen and formalin fixed specimens were used for Southern blot analysis. Thirty-seven of 46 neuroblastomas and 7 of 9 ganglioneuromas were analyzed. Seven neuroblastomas and none of the ganglioneuromas showed N-myc gene amplification. All children with amplified tumours, including three infants, had advanced disease at diagnosis and aggressive course of disease. However, follow-up time was short for the two cases still alive. The use of an ultrasound guided cutting needle biopsy technique for obtaining the required tissue at diagnosis was evaluated in some cases. This technique appeared to be safe and clinically useful since early prognostic information was obtained. Using an imprint from the needle biopsy, the representativity could be confirmed. Ultrasound guided cutting needle biopsies can thus be used routinely to obtain N-myc gene amplification data prior to initiation of therapy in neuroblastoma.
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PMID:N-myc gene amplification in neuroblastoma: a clinical approach using ultrasound guided cutting needle biopsies collected at diagnosis. 160 50

We have isolated a novel human gene encoding a helix-loop-helix (HLH) protein by molecularly cloning chromosome 1p36-specific CpG islands. The gene termed heir-1 was localized to the neuroblastoma consensus deletion at 1p36.2-p36.12. Its predicted protein is 95.8% identical to the mouse HLH462 protein and has clear homology to the mouse Id and Drosophila emc proteins. Heir-1 does not encode a basic DNA binding domain as found in basic HLH proteins. The gene is expressed specifically at high abundance in adult lung, kidney and adrenal medulla, but not in adult brain. Despite prominent heir-1 expression in adrenal medulla, which is a prime target for neuroblastomas, 10 out of 12 neuroblastoma-derived cell lines revealed very low levels of heir-1 mRNA. Low heir-1 expression was generally found in tumor cell lines with N-myc overexpression, whereas the two cell lines displaying high heir-1 levels did not overexpress N-myc. Mutually exclusive expression of both genes was also found by in situ hybridization in developing mouse tissues, particularly in the forebrain neuroectoderm. We conclude that heir-1 expression is reduced specifically in the majority of neuroblastomas and suggest an inverse correlation between heir-1 and N-myc expression in neuroblastoma tumors and in embryonic development.
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PMID:Mutually exclusive expression of a helix-loop-helix gene and N-myc in human neuroblastomas and in normal development. 162 20

D-Alpha-tocopheryl succinate (vitamin E succinate) at a concentration of 11.3 microM inhibited growth and reduced the expression of c-myc, N-myc and H-ras specific mRNAs in murine neuroblastoma cells (NBP2) in culture. R020-1724 [4-(3-butoxy-4-methoxybenzyl)-2- imidazolidinone], an inhibitor of cyclic AMP phosphodiesterase, also inhibited growth and reduced the expression of these oncogenes. Vitamin E succinate treatment caused the formation of two c-myc related transcript of 1.9 and 3.7 kb; however, R020-1724 treatment did not. These results suggest that the inhibition of growth is sufficient to reduce the expression of c-myc, N-myc and H-ras in NB cells in culture, but it is not sufficient to produce two c-myc related transcripts.
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PMID:Effect of vitamin E succinate and a cAMP-stimulating agent on the expression of c-myc and N-myc and H-ras in murine neuroblastoma cells. 164 46

Using test plasmids containing the SV40 origin, we found a wide spectrum of permissiveness to their replication in different human cell lines. N-myc overexpressing neuroblastoma cells were highly permissive. LA-N-1 neuroblastoma cells were the most permissive of all the cell lines that we tested including the homologous CV-1 or COS-1 monkey kidney cells. Other human cell lines expressing various amounts of c-myc, and the 293 cell line expressing adenovirus E1A and E1B exhibited intermediate levels of permissiveness. T24 and EJ bladder carcinoma cells, which do not express the myc genes, were nonpermissive. Transient expression of c-myc or N-myc from plasmid vectors resulted in a modest stimulation of replication. Replication of test plasmids containing different configurations of the SV40 origin region was activated by the myc proteins. The high efficiency of replication in LA-N-1 cells is due to a combination of reasons including the overproduction of N-myc, high efficiency of expression of the SV40 replication initiator protein large T antigen from a cotransfected expression plasmid (containing the T antigen gene under the RSV LTR control), and other unknown host cell replication stimulatory factors. Replication of test plasmids was not detected in N-myc or c-myc overexpressing cells when the T antigen expression plasmid was not provided, showing that the myc proteins cannot substitute for T antigen in SV40 DNA replication.
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PMID:Efficient replication of plasmids containing the SV40 origin in N-myc overexpressing human neuroblastoma cells. 165 Apr 40


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