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)

Genomic amplification of N-myc is an important prognostic indicator in neuroblastoma. The tumors with amplified N-myc are initially sensitive to chemotherapy but often acquire resistance to therapy, recur, and ultimately kill the patients. We measured amplification and expression of N-myc and expression of mdr-1 in 35 surgically resected neuroblastomas, before acquisition of drug resistance and in 4 recurrent tumors resistant to chemotherapy. The mdr-1 mRNA expression was found to be inversely correlated with the N-myc expression. The mdr-1 gene expression was at a low level in advanced stage and histologically undifferentiated neuroblastomas, the same group of tumors in which N-myc expression is elevated. A significantly better prognosis was noted in those patients whose tumors had a high level of mdr-1 expression and a low level of N-myc expression. The role, if any, of increased expression of mdr-1 in the acquisition of multidrug resistance in neuroblastoma remains unclear. However, the aggressive clinical behavior associated with N-myc amplification and/or expression appears to be linked to down-regulation of mdr-1 expression.
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PMID:Inverse correlation between expression of multidrug resistance gene and N-myc oncogene in human neuroblastomas. 218 79

Amplification is one mechanism for activation of oncogenes and results in an excess of DNA template, which can lead to overproduction of oncogene-specific RNA and protein. Amplification of oncogenes has been observed in different tumor tissues. In certain cases amplification and overexpression of particular oncogenes have been correlated with tumor progression and clinical behavior. The best example is neuroblastoma in which the N-myc oncogene frequently is found to be amplified. Over 1,000 patients with breast cancer have been studied for amplification of the c-erbB-2 oncogene until now. The evidence from the studies that amplification of c-erbB-2 is correlated with poor prognosis is in our opinion not convincing. More and more investigations about oncogenes and disease prognosis will take place rather at the protein level than at the DNA level.
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PMID:Amplification of oncogenes and disease prognosis. 218 30

Class I major histocompatibility complex (MHC) antigen expression in neuroblastoma may play a role in the oncogenicity of this embryonal tumor of childhood. Since N-myc amplification in neuroblastoma tumors is associated with rapid tumor progression (33) and N-myc decreases Class I MHC antigen expression in rat neuroblastoma cells (21), we quantitated levels of N-myc mRNA and Class I MHC cell surface antigens in a panel of 24 human neuroblastoma cell lines. We found that N-myc expression is not invariably associated with low levels of beta 2-microglobulin (B2M) and Class I MHC antigen expression. As we considered that Class I MHC antigens may be regulated in association with the differentiation stage of the neuroblastoma tumor, we examined the expression of B2M during development of the human adrenal medulla, the tissue of origin of most neuroblastomas. We found that B2M is a marker of differentiated adrenal medullary cells, expressed late during the third trimester of development. Moreover, using morphological and immunological criteria, we found that B2M is expressed in differentiated tumor cells. These data suggest that the expression of B2M in neuroblastoma is associated with the stage of differentiation of the tumor cell and not N-myc expression. Furthermore, these findings suggest that neuroblastomas may correspond to the arrested differentiation of adrenal neuroblasts at different stages of development.
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PMID:Beta 2-microglobulin expression in human embryonal neuroblastoma reflects its developmental regulation. 218

We studied the clinical significance of genomic amplification of N-myc in Stage IV-S neuroblastoma, with reference to spontaneous regression. Among 103 neuroblastomas in which N-myc was measured, ten were Stage IV-S (eight children were younger than and two were older than 1 year of age). The number of copies of N-myc was 1 to 3 in five patients, four to ten in one patient, and more than ten in four patients, and the survivors of each group were four, one, and one (recurrent), respectively. Of 41 patients younger than 1 year of age, N-myc amplification of more than three copies was found only in Stage IV-S neuroblastoma. Cure with a tendency to regress spontaneously was seen in five of eight patients younger than 1 year of age. However, two patients older than 1 year of age classified as Stage IV-S (one with N-myc amplification) died of progressive disease. In two patients (1 and 3 months of age) with a huge hepatic involvement and in whom the tumor had an amplified N-myc of more than ten copies, tumor regression occurred but there was a relapse to a progressive state later. The overexpression of N-myc mRNA occurred in nine of ten stage IV-S tumors and did not correlate with the prognosis. The vanillylmandelic acid (VMA) to homovanillic acid (HVA) ratio was low in tumors with an increased number of copies of N-myc. Serum lactate dehydrogenase (LDH) levels were increased in Stage IV-S patients with N-myc amplification but not in those with regressing tumors and without N-myc amplification. These data suggest that N-myc amplification may affect the final outcome in the patient classified as Stage IV-S, but tumor regression can occur early after birth and appears to be independent of N-myc amplification.
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PMID:N-myc oncogene and stage IV-S neuroblastoma. Preliminary observations on ten cases. 219 87

Neuroblastomas often show amplification and high expression of the N-myc oncogene. N-myc expression could be explained as a consequence of gene amplification, but an alternative possibility is that expression primarily results from the inactivation or loss of some factor that normally represses the N-myc gene. To test this idea, we fused N-myc-overexpressing neuroblastoma cell lines with lines that do not express N-myc. In the resulting hybrids, N-myc expression turned out to be switched off, although amplified N-myc copies were still present. This suggests that N-myc overexpression in neuroblastomas results, at least in part, from the inactivation of a suppressor gene that is present in normal cells. In rat neuroblastomas, it has been found that N-myc can switch off class I major histocompatibility complex (MHC) expression. Therefore, we analyzed in our hybrid cells whether suppression of N-myc results in reexpression of human class I MHC genes. Because this was found to be the case, the picture emerges of a hierarchic pathway that connects a putative tumor-suppressor gene with the expression of N-myc and consequently of class I MHC, thus affecting the potential immunogenic properties of neuroblastomas.
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PMID:N-myc expression switched off and class I human leukocyte antigen expression switched on after somatic cell fusion of neuroblastoma cells. 220 14

Effects of cyclopentenone prostaglandins, delta 12-prostaglandin (PG) J2 and PGA2 on the expression of N-myc in relation to the effects on cell cycle progression were investigated using human neuroblastoma cell line GOTO. Both PGs suppressed N-myc expression within several hours prior to inducing G1 arrest. The N-myc suppression with delta 12-PGJ2 was continued but with PGA2 it was gradually released, followed by the release of G1 arrest. These results suggest that delta 12-PGJ2 and PGA2 inhibit cell cycle progression in strong association with N-myc suppression and delta 12-PGJ2 is more potent and has a longer effect than PGA2.
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PMID:N-myc suppression and cell cycle arrest at G1 phase by prostaglandins. 222 77

Fucoxanthin, a natural carotenoid prepared from brown algae, inhibited the growth of GOTO cells, a human neuroblastoma cell line. Fucoxanthin at 10 micrograms/ml reduced the growth rate of GOTO cells to 38% of the control at day 3 after drug treatment. Flowcytometric analysis revealed that fucoxanthin caused the arrest in the G0-G1 phase of cell cycle. Expression of N-myc gene was proved to be decreased by fucoxanthin as early as 4 h after treatment at 10 micrograms/ml and that may be important for the mechanism of anti-proliferative action of the carotenoid.
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PMID:Inhibitory effects of fucoxanthin, a natural carotenoid, on N-myc expression and cell cycle progression in human malignant tumor cells. 224 14

Cellular oncogenes appear to be involved in the control of normal cell growth and differentiation. The abnormal activation of these genes in naturally occurring and experimentally induced cancers may have an important role in the expression of the malignant phenotype in cancer cells. Mechanisms for the activation of these genes include chromosomal translocation, point mutation, and DNA amplification. The amplification of specific oncogenes correlates with clinical prognosis in several human malignancies, including breast cancer and neuroblastoma. We examined 21 fresh-frozen human squamous cell carcinomas of the aerodigestive tract for amplification of 10 known cellular oncogenes (c-myc, N-myc, L-myc, N-ras, H-ras, K-ras, erb-B, erb-B2, raf, and int-2), using Southern blotting techniques. Eleven of 21 tumors demonstrated a two-fold to 11-fold amplification of the int-2 oncogene, one member of a family of genes related to basic fibroblast growth factor. Amplification of c-myc, a gene that codes for a DNA-binding protein involved in the regulation of cell growth, was seen in two tumors. None of the other eight genes studied were amplified in any of the tumor specimens.
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PMID:Oncogene amplification in squamous cell carcinoma of the head and neck. 224 38

The correlation between N-myc gene amplification and heretofore known prognosis-associated factors was studied in 23 cases of neuroblastoma, comprising a total of 29 tumors (23 primary and six metastatic), examined in and after 1983. DNAs were extracted from tumor tissues preserved at -70 degrees C and digested with the restriction enzyme EcoRI. Southern blotting analysis was performed on these DNAs with the N-myc probe labelled with alpha-32P-dCTP. Prognosis-associated factors studied were age at diagnosis, stage, primary site, histological type, blood biochemistry tests, and catecholamine metabolites in urine. Amplification of N-myc gene was observed only in the cases in which primary site was the adrenal gland, but the relation to the stage, histological type, and prognosis was not as apparent as reported by other investigators. However, the amounts of catecholamine metabolites were low in the cases with amplification, and this suggests immaturity of catecholamine metabolism in the tumor with N-myc gene amplification.
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PMID:N-myc gene amplification and other prognosis-associated factors in neuroblastoma. 226 66

We have recently identified and cloned the gene for a cytosolic polypeptide, designated oncoprotein 18 (Op18), which is expressed in acute lymphocytic leukemia and some solid tumors including neuroblastoma. Op18 is phosphorylated upon treatment of lymphoid cells with phorbol myristate acetate. We have proposed that unphosphorylated Op18 plays a role in cellular proliferation, and that its phosphorylated forms, namely Op18a and Op18b, are associated with diminished cell proliferation. In this study, we report that in neuroblastoma tumors, the phosphorylation of Op18 was substantially diminished with increasing N-myc gene copy number. Treatment of the neuroblastoma cell line SMS-KCNR, which contains 75 copies of the N-myc gene, with retinoic acid for ten days resulted in an increase in Op18 phosphorylation. Our findings provide evidence for distinct patterns of Op18 phosphorylation in neuroblastoma tumors with and without N-myc gene amplification.
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PMID:N-myc gene amplification in neuroblastoma is associated with altered phosphorylation of a proliferation related polypeptide (Op18). 226 30


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