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)

Congenital neuroblastoma and nesidioblastosis occurred simultaneously in a neonate with severe hypoglycemia. This combination may represent a rare type of complex neurocristopathy. Immunocytochemical staining revealed a diffuse proliferation of alpha, beta, and delta cells as clusters and individual cells. The total islet volume was less than control values and beta cell counts were not increased. This case tends to support the hypothesis that morphologic integrity of the normal islet architecture is important in the control of function and not merely excessive numbers of one cell type.
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PMID:Nesidioblastosis and congenital neuroblastoma: a histologic and immunocytochemical study of a new complex neurocristopathy. 38 94

The activity of nuclear DNA polymerases alpha, beta and delta/epsilon, uracil-DNA glycosylase, thymidine kinase and the presence of Proliferating Cell Nuclear Antigen (PCNA) have been examined in developing rat glial cells, in rat and human glioma, in human neuroblastoma and in differentiated neuroblastoma cell lines in vitro. During glial development the activity of all enzymes tested, except DNA polymerase beta, markedly decreased, suggesting their coordinate regulation in respect to the proliferative state of the cells. Glioma and neuroblastoma cell lines restore the enzymatic activities that were no longer expressed in normal adult cells. Neuroblastoma cell lines induced to differentiate in vitro by retinoic acid showed a decline of the activities of DNA polymerase alpha, DNA polymerase delta/epsilon, uracil-DNA glycosylase and thymidine kinase similar to that observed during in vivo differentiation. We also demonstrate that PCNA is not detectable in glial and neuronal cells at all developmental stages, but can be found in tumor nerve cells. A possible use of enzymatic assays or anti-PCNA antibodies to detect brain tumors is discussed.
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PMID:DNA synthesis enzymes and proliferating cell nuclear antigen in normal and neoplastic nerve cells. 135 31

Retinoids are known to have profound effects on cellular differentiation and embryo pattern formation. In the adult organism, retinoid acid (RA) receptors are present in a large variety of tissues, including brain. However, little is known of the precise roles of RA at these different sites. In the present study we have identified a novel potential target of RA action by identifying an RA response element (RARE) in the human oxytocin (OT) gene promoter. We have used DNA-mediated gene transfer techniques to introduce various portions of the OT 5'-flanking sequences next to the chloramphenicol acetyltransferase (CAT) gene in neuroblastoma cells. RA elicited a marked stimulation of the transcriptional activity of the OT promoter in cells cotransfected with either the human RA receptor alpha, beta, or gamma. In cells cotransfected with the RA receptor alpha, the ED50 of this response was 5 x 10(-10) M. The RA response could also be conferred to a heterologous promoter independent of orientation. 5'-Deletions as well as site-directed mutations demonstrated that four TGACC motifs, located at -162, -156, -103, and -83 in the OT promoter, are necessary for optimal RA induction. Mutation or deletion of any of these elements reduces significantly the RA response. Interestingly, the first two TGACC motifs overlap with the estrogen response element that we have previously characterized in this gene. Furthermore, the TGACC motif located at -83 overlaps with the CCAAT box. We further demonstrate that in neuroblastoma cells transfected with an RAR alpha expression vector expression of the endogenous OT gene is stimulated greater than 4-fold in response to RA. Our studies constitute the first report of a RARE in a neuropeptide gene and define a mechanism by which OT gene expression can be modulated by retinoic acid.
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PMID:Identification of a retinoic acid response element in the human oxytocin promoter. 165 67

Potentially lethal damage repair (PLDR) in human cells was investigated by delayed plating experiments with three malignant tumor cell lines (breast, colon and neuroblastoma) and two normal diploid lines (lung fibroblasts) in exponential and plateau phases. All cell lines demonstrated PLDR which was considerably higher for all the cell lines in plateau phase compared to log phase. At survival levels of 0.01, the two fibroblast lines had recovery ratios of 3.8 and 4.0 for 6 h delayed plating in plateau phase. The malignant lines showed recovery ratios of 5.7 (neuroblastoma), 3.2 (breast carcinoma) and 2.4 (colon carcinoma). The data were fitted to the linear quadratic equation and in addition, a repair factor was developed to compare survival for immediate and delayed plating: S(D) = exp[-gamma (alpha D + beta D2)] where gamma = 1 for immediate plating. Previously published data on human tumor and normal lines were also fitted to this equation. In all instances the three parameter equation (alpha, beta, gamma) allowed a good fit of the survival data for immediate and delayed plating. By using the same alpha, beta for the zero hour and 6 h survival curves, the gamma factor allows a much more useful method of comparing PLDR among different cell lines. The gamma factor for the two lung fibroblast lines were 0.70 and 0.71 while skin fibroblasts also had a 0.71 factor. The six malignant lines ranged from 0.62 to 0.93 with all but the neuroblastoma line having a higher factor (and therefore decreased PLDR capacity) than the normal lines. No correlation between PLDR and in vitro radiosensitivity or clinical radiosensitivity of the tumor type was found.
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PMID:Potentially lethal damage repair in human cells. 360 30

The relative inhibitory potency of prostaglandin A (PGA) and prostaglandin J2 (PGJ2) analogues compared to prostaglandin A1 (PGA1) was determined in a clonogenic assay system. Three human melanoma cell strains (C8146A, C8146C, and C8161), a human melanoma cell line (M1RW5) and a human neuroblastoma cell line (IMR-32) were used. Prostaglandin analogues were screened in the clonogenic assay system and the dose effect curves were analyzed by linear regression utilizing the median effect relationship. The computer-generated 50% and 95% inhibitory doses showed that 15-deoxy-16-hydroxyl-16-vinyl-prostaglandin A2 (DHV-PGA2) was from two- to three-fold more active than PGA1 in inhibiting the clonogenic growth of human melanoma cells. Based on the 50% inhibitory dose, PGJ2 and its analogues were from two to five times more potent than PGA1. The delta 12- and delta 12,14-PGJ2 were the most potent of the prostaglandins tested. However, the 95% inhibitory dose for prostaglandin D2 (PGD2), PGJ2 and its analogues against neuroblastoma did not show any enhancement in activity in comparison to PGA1, suggesting that some tumor specificity in the activity of these analogues may be signified by the neuroblastoma data. Prostaglandins which contained a fluoride substitution at position 11 were also tested for activity. As we previously observed with other analogues which did not contain an alpha, beta-unsaturated carbonyl group in the cyclopentane ring, 9 beta, 15 alpha-dihydroxy-11 beta-fluoroprosta-5-cis-13-trans-dienoic acid and 9 alpha, 15 alpha-dihydroxy-11 beta-fluoroprosta-5-cis-13-trans-dienoic acid did not inhibit the clonogenic growth of human melanoma cells. Administration s.c. to established human melanoma tumors growing in athymic nude mice caused a significant growth inhibition. The treatment schedules ranged from 1 to 8 days. Injection s.c. of PGA1 at a dose of 40 mg/kg/day resulted in a 20% suppression in tumor growth. Higher doses (100 and 200 mg/kg/day) effected an 80% reduction in tumor growth. The higher doses were associated with reversible toxicities, diarrhea and skin inflammation. Administration of DHV-PGA2 at a dose of 20 mg/kg/day resulted in 40% reduction in tumor growth. The increased in vivo potency of DHV-PGA2 corresponds to the results obtained in the clonogenic assay system.
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PMID:Inhibition of human melanoma growth by prostaglandin A, D, and J analogues. 369 5

Enolase isozymes (alpha, beta and gamma enolases) in the extracts of pediatric tumors (neuroblastoma, ganglioneuroblastoma, rhabdomyosarcoma and Wilms' tumor) were determined by means of enzyme immunoassay systems. All tumor tissues examined contained alpha enolase at high levels (2070-19100 ng/mg protein). The beta and gamma enolases were present at high levels particularly in rhabdomyosarcoma (886 +/- 750 ng/mg protein) and (ganglio)neuroblastoma (2060 +/- 890 ng/mg protein), respectively. Immunohistochemical studies confirmed these results. Serum levels of these enolase isozymes were also determined in pediatric tumor patients. Before treatment, a serum sample from a patient with rhabdomyosarcoma contained a high level of beta enolase and serum samples from patients with (ganglio)neuroblastoma contained high levels of gamma enolase. However, the levels of serum beta and gamma enolases were low in patients with Wilms' tumor. The elevated level of beta or gamma enolase in serum from rhabdomyosarcoma or (ganglio)neuroblastoma patients was markedly decreased after adequate treatment (operation, chemotherapy or radiation). The results indicated that the enolase isozymes are useful marker antigens for differential diagnosis and therapeutic monitoring of neuroblastoma and rhabdomyosarcoma.
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PMID:Enolase isozymes as markers for differential diagnosis of neuroblastoma, rhabdomyosarcoma, and Wilms' tumor. 632 51

Enolase catalyzes the interconversion of 2-phosphoglycelate and phosphoenolpyruvate in the glycolytic pathway. Enolase isozymes are dimers formed from three subunits (alpha, beta, and gamma). The gamma subunit, containing enolase (gamma-enolase) in serum, is important in the diagnosis of tumors originating from APUD (amine precursor uptake and decarboxylation) cells, like neuroblastoma, small cell carcinoma for the lung and certain carcinomas of the thyroid, the pancreas and the gut. Therefore, the determination of serum gamma-enolase levels is useful as a tumor marker of these neoplasms. On the other hand, raised gamma-enolase levels in cerebrospinal fluid have been demonstrated in patients suffering from various neurological disorders. In this paper, the author reviews the results of some of many studies related to gamma-enolase, up to now.
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PMID:[Gamma-enolase (gamma-eno)]. 760 91

We have examined the 5'-flanking region (944 bp) of the human choline acetyltransferase (hChAT) gene for sequences that modulate its transcriptional activity and identified a sequence 5'-TGACCCA-3' which confers c-Jun/c-Fos (AP-1) inducibility of homologous and heterologous promoters. Using transient transfections in neuroblastoma NE-1-115 and COS-1 cells, we show that ligand-activated estrogen receptor (HEGo) represses the transcriptional activation by c-Fos/c-Jun. Testing HEGo mutants in transfection assays reveals that the ligand-binding domain is crucial for this repression, whereas the N-terminal (A/B) region and the DNA-binding domain are not essential. Gel retardation assays show that the hChAT AP-1 recognition sequence binds in vitro baculovirus-produced c-Jun/c-Fos proteins. This binding is inhibited by addition of baculovirus-produced HEGo. In contrast to HEGo, ligand-activated glucocorticoid, androgen, and retinoic acid receptors (RARs) enhance the transcription activation induced by c-Jun/c-Fos. All three types of RARs--RAR alpha, beta, gamma--and RXR alpha are able to stimulate AP-1 activity on the proximal hChAT promoter. Several mechanism possibilities involving protein-protein interaction are discussed to explain the phenomena.
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PMID:Positive and negative effects of nuclear receptors on transcription activation by AP-1 of the human choline acetyltransferase proximal promoter. 774 8

A phospholipase-C-linked nucleotide receptor, sensitive to both uridine and adenosine triphosphate (UTP and ATP) has been cloned from NG108-15 neuroblastoma x glioma hybrid cells. We have tested whether activation of this receptor could inhibit the voltage-dependent K+ current [IK(M) or "M-current"] in NG108-15 cells recorded using whole-cell patch-clamp methods. Both UTP and ATP inhibited IK(M) by 44% and 42%, respectively, at 100 microM. Mean IC50 values were: UTP, 0.77 +/- 0.27 microM; ATP, 1.81 +/- 0.82 microM. The order of nucleotide and nucleoside activity at 100 microM was: UTP = ATP > ATP [gamma S] = ITP > 2-MeSATP > ADP = GTP >> AMP-CPP, adenosine, where ATP[gamma S] is adenosine 5'-O-(3-thiotriphosphate), ITP is inosine 5'-triphosphate, 2-MeSATP is 2-methylthio ATP and AMP-CPP is alpha, beta methylene ATP. This rank order accords with their activities at the cloned P2U receptor. Effects were not inhibited by suramin (up to 500 microM) or by pre-incubation for 12 h in 500 ng.ml-1 Pertussis toxin. Inhibition of IK(M) was frequently preceded by a transient outward current, probably a Ca(2+)-activated K+ current, responding to Ca2+ mobilization. No effect on the delayed rectifier K+ current was observed. These observations match those expected from stimulating other phospholipase-C-linked receptors in NG108-15 cells.
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PMID:Activation of nucleotide receptors inhibits M-type K current [IK(M)] in neuroblastoma x glioma hybrid cells. 789 8

The protein kinase C (PKC) alpha, beta and epsilon isoforms have distinct nuclear localizations in neuroblastoma x glioma hybrid cells NG 108-15. We found by immunoblotting that PKC alpha, beta II, delta and epsilon are the predominant isoforms in these cells. In contrast to other neuronal cell lines, none of these isoforms is down-regulated during differentiation. Confocal immunofluorescence microscopy revealed that in undifferentiated cells PKC alpha is located in the cytoplasm and in the nucleus excluding nucleoli. In differentiated cells PKC alpha was almost exclusively located in the cytoplasm. Stimulation of the cells with phorbol ester resulted in translocation to the plasma membrane. PKC beta II was not detectable in the nuclei. PKC delta was found in the nucleoli and in the cytoplasm, in differentiated cells particularly in the neurites. Phorbol ester failed to induce a translocation to other compartments. PKC epsilon was localized with the nuclear-pore complexes at the nuclear envelope. In differentiated cells after stimulation with phorbol ester, partial translocation to the plasma membrane was observed.
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PMID:Differential nuclear localization of protein kinase C isoforms in neuroblastoma x glioma hybrid cells. 802 Apr 72


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