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)

Levels of serum manganese superoxide dismutase (Mn-SOD) in normal children aged from 1 to 14 years and children with various hematological and malignant diseases were determined by enzyme-linked immunosorbent assay (ELISA). In the normal children, the serum Mn-SOD levels gradually increased in proportion to age. By 8 years of age, the Mn-SOD level was nearly at the adult level. The normal values of serum Mn-SOD (mean +/- SD) of children below 4 and above 8 years old were 48 +/- 10.2 ng/ml and 84 +/- 22.5 ng/ml, respectively. Assuming the upper limit of normal Mn-SOD level in serum to be the mean value +/- 2 SD of children at each age, high serum levels of Mn-SOD were found for 8 of 12 patients with neuroblastoma, three of four patients with Wilms tumor, and four of five patients with acute myeloid leukemia. The patients with neuroblastoma exhibited a transient increase in Mn-SOD following chemotherapy, but after 1 week the levels decreased markedly to the control levels. The changes in serum Mn-SOD levels in the patients with neuroblastoma correlated well with the levels of neuron-specific enolase. Mn-SOD was intensely stained in bone marrow cells of patients whose cancer cells had moved into the bone marrow. High levels of Mn-SOD were also found in cultured human neuroblastoma cells. These data indicate that Mn-SOD is expressed in neuroblastoma cells, may serve as one of the diagnostic and prognostic markers for the neuroblastoma, and may be useful to predict the effectiveness of chemotherapy for neuroblastoma and the recurrence of this disease.
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PMID:High levels of Mn-superoxide dismutase in serum of patients with neuroblastoma and in human neuroblastoma cell lines. 131 10

Six independent clonal isolates from a morphologically heterogeneous human neuroblastoma cell line stably expressed several products of the human amyloid precursor protein (APP) from an introduced DNA construct; the "substrate-adherent" phenotype (fibroblast-like cells) predominated in all 6; these displayed immunoreactivity of vimentin, but little to no reactivity of neuron-specific enolase. A stably transfected isolate which did not show any expression from the identical construct (presumably because of a position effect) exhibited the predominantly neuronal phenotype of the parental cells (neuron-specific enolase positive). These results suggest selective neurotoxicity of the expressed products. Two of the 6 stably expressing cell lines showed a decrease of native mRNA for APP to levels that were 1/4-1/3 that of the parental cells and a decrease of their growth rates to half that of the parental cells; these decreased growth rates were improved by conditioned medium from the parental cell line. Western blot analysis revealed at least four distinct fragments of the COOH-terminus of APP in the isolate which expressed protein and mRNA in greatest abundance, suggesting that overexpression of APP in a human neural cell line leads to aberrant cleavage of APP.
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PMID:Expression of a carboxy-terminal region of the beta-amyloid precursor protein in a heterogeneous culture of neuroblastoma cells: evidence for altered processing and selective neurotoxicity. 133 98

1. The effects of retinoic acid, gamma-interferon, cytosine arabinoside, nerve growth factor, tumor necrosis factor, and 12-O-tetradecanoylphorbol 13-acetate on the human neuroblastoma cell line, LAN-5, were studied. Intracellular levels of acetylcholinesterase, neuron-specific enolase, catecholamines and related neurotransmitters, vasointestinal peptide, and substance P were evaluated after induction. 2. Cell morphology was strongly affected by retinoic acid, gamma-interferon, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate. The main effects of retinoic acid and gamma-interferon were the loosening of cell clusters and the extension of long neurites; cytosine arabinoside induced cell body swelling and marked neuritogenesis. Following 12-O-tetradecanoylphorbol 13-acetate treatment, the cells became small, round, and neuritic. Conversely, modifications induced by nerve growth factor and tumor necrosis factor were mild. Cell proliferation rate was reduced by retinoic acid, gamma-interferon, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate, while nerve growth factor and tumor necrosis factor were devoid of effects. 3. Acetylcholinesterase activity was significantly stimulated by retinoic acid and by gamma-interferon. Neuron-specific enolase activity was unaffected by all treatments except 12-O-tetradecanoylphorbol 13-acetate, which enhanced it by 1.6-fold. 4. The cellular catecholamine and related metabolite content was lowered by retinoic acid and gamma-interferon, while cytosine arabinoside and, even more, 12-O-tetradecanoylphorbol 13-acetate showed a stimulatory activity on their intracellular accumulation. 5. Finally, the cell-associated vasointestinal peptide level was strikingly increased by gamma-interferon and, to a lesser extent, by retinoic acid, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate. 6. It is concluded that the most relevant biochemical changes associated with LAN-5 cells differentiation involve the repertoire of neurotransmitters and neuropeptides. These events vary in quality and in quantity, likely due to the pattern complexity of gene expression triggered by each inducer in determining the diversity of neuronal phenotypes.
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PMID:A combined evaluation of biochemical and morphological changes during human neuroblastoma cell differentiation. 135 48

Two clonal immortalized neurons designated CL8c4.7 and CL8a5.2 were established by somatic cell fusion between a hypoxanthine phosphoribosyltransferase-(HPRT-) deficient neuroblastoma N18TG2 and newborn mouse cerebellar/brain stem neurons. In the serum-containing medium without extra differentiating agents, both clones exhibited a morphology of differentiated neurons. They contained high levels of glutamate but no gamma-aminobutyric acid (GABA). The CL8a5.2 clone synthesized choline acetyltransferase and serotonin. In immunocytochemical studies, both clones expressed 200 kD neurofilament protein, neuron-specific enolase, microtubule-associated protein 2 (MAP2), tau protein, neuronal cell adhesion molecule (N-CAM), HNK-1, Thy-1.2, saxitoxin-binding sodium channel protein, and glutamate. Synaptophysin immunoreactivity was identified in the neuritic terminals of CL8c4.7 cells. Most of these antigens were barely detectable on N18TG2 cells. Electrophysiologically, both clones generated action potentials in response to electrical stimuli. The hybrid clones that express characteristics of differentiated neurons derived from the cerebellar and brain stem regions might be invaluable for the study of the molecular basis of neuronal differentiation and degeneration in these regions.
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PMID:Establishment of mouse-immortalized hybrid clones expressing characteristics of differentiated neurons derived from the cerebellar and brain stem regions. 135 6

Infectivity of human T-lymphotropic virus type I (HTLV-I) to human nervous tissue cells was explored using co-cultivation with X-irradiated, HTLV-I-producing MT2 cells. Examined cells included normal cerebellar cells, brain tumor cells (astrocytoma, medulloblastoma, meningioma, hemangioblastoma, and schwannoma), and various cell lines (astrocytoma, ependymoma, oligodendroglioma, medulloblastoma, and neuroblastoma). Successful HTLV-I infection was confirmed immunohistochemically using monoclonal antibodies to HTLV-I p19, p24, and pX product. All cell lines and primary cultures from normal cerebellar tissues and brain tumors could be infected with HTLV-I. Double immunostaining showed that glial fibrillary acidic protein-, S-100 protein- or vimentin-positive cells were susceptible to infection. Neurofilament- or neuron-specific enolase-positive cells in medulloblastoma could also be infected. Reverse-transcriptase assay revealed the productive infection in U251-MG (astrocytoma) and KG-IC (oligodendroglioma) lines. Co-cultivated U251-MG cells formed syncytial polykaryons after serial passages, and polymerase chain reaction assay detected HTLV-I genome in U251-MG syncytial polykaryons and p19+ mononuclear cells. HTLV-I viral RNA was also detected in infected U251-MG cells by in situ hybridization. These data show that HTLV-I may have a wide spectrum of infectivity in human nervous tissues.
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PMID:Infectivity of human T-lymphotropic virus type I to human nervous tissue cells in vitro. 138 59

In 211 patients with neuroblastoma, serum vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels were determined and correlated to stage, histological differentiation, ferritin, neuron-specific enolase, lactate dehydrogenase (LDH) and outcome. Elevated serum VMA and/or HVA levels were found 16% less frequently than elevated urine levels. The incidence of the elevated serum levels increased with stage (stages I-III 58%, IV 78%, IVS 100%). Increased VMA/HVA ratios were not associated with a higher grade of tumour differentiation. Serum ferritin and neuron-specific enolase showed no correlation, and LDH a borderline non-random correlation with the serum catecholamine metabolites. Using age-related reference values a quotient of serum VMA/HVA (P = 0.061) < 0.7 indicated a poorer event-free survival (48 +/- 10%) than ratios > or = 0.7 (event-free survival 81 +/- 6%) for children with localised neuroblastoma (P = 0.0004). No correlation with prognosis was detected for patients with stage IV and stage IVS disease. We conclude that serum VMA and HVA determinations may be useful as tumour markers for 71% of neuroblastoma patients, and aid in estimating the prognosis in children with localised disease.
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PMID:Serum vanillylmandelic acid/homovanillic acid contributes to prognosis estimation in patients with localised but not with metastatic neuroblastoma. 141 87

To verify the practical utility of immunohistochemical analysis of bone marrow biopsy specimens in patients with neuroblastoma, we compared the results of routine histologic examination of 68 specimens with the results of immunohistochemical detection of tumor cells using an antibody to neuron-specific enolase (NSE). A commercially available polyclonal antibody to this enolase isoform consistently reacted with the neoplastic cells in biopsy specimens with histologic features diagnostic of (24 specimens) or suspicious for (one specimen) metastatic neuroblastoma. Immunohistochemical double-staining techniques documented that the NSE-positive neoplastic cells also reacted with antibodies to chromogranin and synaptophysin. Notably, anti-NSE detected small foci of metastatic neuroblastoma in two of 43 biopsy specimens that showed no evidence of metastatic tumor in the initial histologic sections. Rare NSE-reactive hematopoietic cells were present in approximately a third of the specimens with and those without neuroblastoma and were easily distinguished from metastatic tumor by morphologic examination. We conclude that this antibody to NSE consistently detects neuroblastoma cells in routinely processed bone marrow specimens, including small foci of tumor cells not evident in initial histologic sections.
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PMID:Detection of metastatic neuroblastoma in bone marrow biopsy specimens with an antibody to neuron-specific enolase. 149 35

Certain biological actions of phorbol esters cannot be duplicated by diacylglycerol (DAG). Thus, the human neuroblastoma cell line SH-SY5Y differentiates when exposed to 12-tetradecanoyl-13-acetyl-beta-phorbol (TPA) and protein kinase C (PKC) inhibitors, but not when exposed to DAG. To investigate the specific features of the phorbol diester molecule that might be responsible for these effects, we examined the extension of neurites, expression of neuron-specific enolase, and appearance and localization of phosphorylated high molecular weight neurofilament subunits (NF-H). TPA, 12-deoxy-13-tetradecanoyl-beta-phorbol, and staurosporine, but not DAG or 4-O-methyl-TPA, caused neurite outgrowth. Neuron-specific enolase was expressed in cells treated with TPA and 12-deoxy-13-tetradecanoyl-beta-phorbol but not with DAG, staurosporine, or 4-O-methyl-TPA. NF-H increased in the perikarya of cells treated with DAG and 4-O-methyl-TPA, in processes and to varying degrees in perikarya of TPA- and 12-deoxy-13-tetradecanoyl-beta-phorbol-treated cells, but much more in the processes than in the perikarya of staurosporine-differentiated cells. These findings and additional differences between the differentiation induced by TPA (a PKC activator) and staurosporine (a PKC inhibitor), including distinct morphology of the cell body and processes and time of appearance of the morphological phenotype, suggest that activators and inhibitors of PKC induce differentiation of SH-SY5Y cells by different mechanisms, and that the five-membered/seven-membered terpene ring region present in TPA must be intact for the induction of morphological differentiation.
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PMID:Distinct mechanisms of differentiation of SH-SY5Y neuroblastoma cells by protein kinase C activators and inhibitors. 154 59

Tumour samples from 38 patients with neuroblastoma were analysed for the presence of N-myc amplification. N-myc gene copy number in tumour DNA was determined by Southern blotting, and by dilution analysis where appropriate. Available clinical data, obtained at tissue collection and by subsequent questionnaire included patient age at diagnosis, catecholamine, ferritin and neuron-specific enolase levels, treatment and disease status. This study was designed to investigate the use of N-myc amplification data as an additional indicator for determination of prognosis. Patients with amplified N-myc had more rapid disease progression than those without amplification (P less than 0.005). Stratification of Stage III and IV patients using N-myc amplification permitted identification of a subgroup with poorer prognosis. The results demonstrate that determination of N-myc amplification is important in assessment of prognosis and subsequent treatment in patients with neuroblastoma.
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PMID:Association of N-myc amplification with neuroblastoma: the Australian and New Zealand experience. 155 17

In 42 tumour samples of human neuroblastoma, histological classification by differentiation (Shimada) was significantly correlated with strong positivity for neuron-specific enolase (NSE) and inversely correlated with rosette formation. Most ganglioneuroblastomas were positive for S-100 protein and reacted strongly with NSE antibody. Histological signs of high proliferative activity included intermediate or high mitosis-karyorrhexis index, necrosis and lack of calcification, which were significantly correlated with each other. Flow cytometric DNA analysis demonstrated that 88% of the tumour samples had DNA aneuploid stem lines. High S phase fraction (greater than or equal to 0.20) was significantly correlated with necrosis and lack of calcification. Univariate analysis of prognosis for 26 patients whose tumour samples were obtained before adjuvant treatment showed that five factors were significantly related to a better outcome: early stage of the disease (stages I, II, IV-S), S phase fraction less than 0.20, favourable Shimada histology, positivity for S-100 protein, and strong positivity for NSE. In multivariate analysis, only S phase fraction or stage of disease remained significantly associated with prognosis. DNA index did not correlate with prognosis in this study.
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PMID:Prognostic importance of DNA flow cytometrical, histopathological and immunohistochemical parameters in neuroblastomas. 159 94


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