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)

I 131-metaiodobenzylguanidine (MIBG) is an aralkylguanidine with certain structural similarities to norepinephrine (NE). It is concentrated, stored, and released from chromaffin granules in a manner almost identical with that of NE. It will image the enlarged adrenal medullae of adrenal medullary hyperplasia when the CAT and NMR scans are normal. It is more sensitive in detecting extra-adrenal pheochromocytomas than CAT and NMR imaging. Because 46% of our 176 patients with histopathologically proved "benign" pheochromocytomas (pheos) have developed demonstrable metastases, with or without elevated plasma and urinary catecholamines, we now image all patients with "benign" pheos yearly. As of January 22, 1986 we had treated 28 patients with malignant pheos 71 times with MIBG. As of July 24, 1986, we had given 34 neuroblastoma patients 55 tracer doses. In some cases MIBG demonstrates more neuroblastoma than all other imaging modalities and this is helpful in staging. We have had 30-50% objective regressions in neuroblastoma tumor mass in 3 out of the first 12 patients treated. These three patients had slower-growing tumors and a lower body burden than the nonresponders. We also record the sensitivity of MIBG imaging of neuroendocrine tumors other than pheos and neuroblastomas.
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PMID:Update on basic research and clinical experience with metaiodobenzylguanidine. 330 1

Between 7/3/80 and 5/7/86 we gave 32 of our neuroblastoma patients 62 diagnostic doses of metaiodobenzylguanidine (MIBG) and 12 patients 20 treatment doses. Our conclusion from our diagnostic dose studies is that MIBG should be used for staging the extent of neuroblastoma before therapy is started, because it may change the proposed staging and therapy. In MIBG therapy for neuroblastoma, our criteria for agreeing to treat a patient are based on calculations from a 4-day tracer dose study that assures that the patient will receive from his first therapy dose a tumor dose of at least 2,000 rads/100 mCi, with a total body dose of not greater than 200 rads. Under these circumstances in children, the blood dose has been about 50 rads. The platelet count falls routinely with a 150-rad whole-body dose but never to dangerous levels. We have delivered tumor doses of 7,000-34,600 rads on the first dose using 150-215 mCi. We have had objective regressions (as shown by before and after CAT scans) of 30-59% in volume of the principal tumor mass in 3 of the first 12 patients treated. All patients had Grade IV neuroblastoma with extensive previous surgery, radiation, and chemotherapy, with and without previous bone marrow transplants. MIBG therapy was most effective in patients with slower-growing tumors for whom initial treatment doses were 200 mCi or more.
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PMID:Treatment of neuroblastoma with 131I-MIBG: dosimetric problems and perspectives. 365 5

Patients with dumbbell neuroblastoma present with a wide variety of spinal cord problems. We recently treated an infant with a large dumbbell neuroblastoma who was neurologically intact. Because a CAT scan showed a retroperitoneal mass to be abutting the right vertebral body at T12-L1, a precautionary myelogram was performed, which revealed extensive intraspinal extension. We report this case to emphasize the need to have a high index of suspicion of spinal cord involvement in light of a normal neurologic examination since, any attempt at removing the extraspinal part, first, could cause serious neurologic sequelae. We also wish to emphasize avoiding radiation therapy when the tumor has been removed grossly to lessen the development of kyphoscoliatic deformity. The infant will be routinely followed with serial VMAs and ultrasound.
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PMID:Dumbbell neuroblastoma presenting without spinal cord findings. 379 63

1. The transcriptional regulation of the rat brain L-type calcium channel alpha 1D subunit (RB alpha 1D) gene was investigated using NG108-15 neuroblastoma-glioma cells. 2. Differentiation of NG108-15 cells in the presence of prostaglandin E1 or retinoic acid resulted in the appearance of mRNA encoding the RB alpha 1D subunit detected using Northern blot analysis. 3. A rat genomic DNA library was screened, and a 15.2-kb clone was isolated and partially sequenced which included part of the 5' upstream sequence through the initial part of intron 2 of the RB alpha 1D gene. 4. Deletion analysis, using a CAT reporter gene and transfected NG108-15 cells, revealed that the 1.2-kb 5'-upstream sequence from the RB alpha 1D gene contains cis-acting positive and negative regulatory elements. A deletion of the 3' end of exon 1 also suggested the presence of regulatory elements in the first exon. 5. DNase footprinting of exon 1 of the RB alpha 1D gene revealed two regions protected from digestion by specific protein binding, and the second region included an (ATG)7 trinucleotide repeat sequence. Electrophoretic mobility shift assays confirmed nuclear protein(s) binding to the (ATG)7 sequence. 6. The (ATG)7 sequence functions as a enhancer when linked to a thymidine kinase promoter and a CAT reporter gene. 7. These results provide the initial description of the transcriptional regulation of the RB alpha 1D gene and identify a novel enhancer that consists of an (ATG)7 trinucleotide repeat sequence.
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PMID:Transcriptional regulation of the neuronal L-type calcium channel alpha 1D subunit gene. 755 31

Synapsin I is implicated in the modulation of neurotransmitter release and in synaptogenesis and is regulated by phosphorylation. The rat and human synapsin I genes both carry CRE and TRE consensus sequences in their promoter regions. This suggested that protein kinase-mediated signal pathways might also regulate synapsin I activity at the level of gene expression and thus contribute, on a slower time scale, to synaptic plasticity. We have therefore investigated, in neuroblastoma cell lines, the effects of agents that activate protein kinases on synapsin I gene expression. Unexpectedly, treatment with forskolin/IBMX was not found to enhance synapsin I mRNA levels. Rather, it causes a decrease to approximately 50% within 1 day although several CRE-dependent control genes are strongly induced. The calcium ionophore, A23187, lowers synapsin I mRNA to approximately 75%, and the phorbol ester, TPA, is without effect. Transient expression of a CAT fusion gene under the control of the synapsin I promoter region is also inhibited by forskolin/IBMX, as well as by protein kinase A (PKA) overexpression, suggesting that the decrease of synapsin I mRNA in response to forskolin/IBMX is due to the inhibition of transcription. Mutation of the CRE consensus does not affect the response to PKA, but it reduces the constitutive activity of synapsin I promoter constructs down to 30-50%. Nuclease footprinting experiments demonstrate sequence-specific binding proteins from brain, liver and NS20Y cell nuclear extracts to the CRE consensus sequence of the rat synapsin I promoter.
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PMID:The CRE consensus sequence in the synapsin I gene promoter region confers constitutive activation but no regulation by cAMP in neuroblastoma cells. 771 Oct 68

Mouse Hoxb-4 (Hox-2.6) is a homeobox gene that belongs to a family which also includes Hoxa-4, Hoxc-4, and Hoxd-4 and that is related to the Deformed gene in Drosophila melanogaster. We have determined the sequence of 1.2 kb of 5' flanking DNA of mouse Hoxb-4 and by nuclease S1 and primer extension experiments identified two transcription start sites, P1 and P2, 285 and 207 nucleotides upstream of the ATG initiator codon, respectively. We have shown that this region harbors two independent promoters which drive CAT expression in several different cell lines with various efficiencies, suggesting that they are subject to cell-type-specific regulation. Through detailed mutational analysis, we have identified several cis-regulatory elements, located upstream and downstream of the transcription start sites. They include two cell-type-specific negative regulatory elements, which are more active in F9 embryonal carcinoma cells than in neuroblastoma cells (regions a and d at -226 to -186 and +169 to +205, respectively). An additional negative regulatory element has been delimited (region b between +22 and +113). Positive regulation is achieved by binding of HoxTF, a previously unknown factor, to the sequence GCCATTGG (+148 to +155) that is essential for efficient Hoxb-4 expression. We have also defined the minimal promoter sequences and found that they include two 12-bp initiator elements centered around each transcription start site. The complex architecture of the Hoxb-4 promoter provides the framework for fine-tuned transcriptional regulation during embryonic development.
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PMID:Multiple positive and negative regulatory elements in the promoter of the mouse homeobox gene Hoxb-4. 796 51

To determine whether over-expression of the MDR1 gene may result from activation of its promoter by differentiating agents, the activity of the human MDR1 proximal promoter (MDR1 pp) transfected to 2 neuroblastoma lines treated with retinoic acid and forskolin was first measured using transient expression assays while the MDR1 mRNA levels were measured by Northern blots. The results indicate that retinoic acid and forskolin were able to activate the human MDR1 pp in a dose dependent manner after transfection of the MDR1pp- CAT constructs in the 2 cell models tested, i.e., SK-N-SH and IGR-N-91, a new human neuroblastoma cell line. A significant increase in MDR1 gene transcript levels was observed upon treatment with differentiation inducers in SK-N-SH but not in IGR-N-91 neuroblasts. These results suggest that the induction of the MDR1 gene promoter is necessary but not sufficient to lead to an increase in MDR1 gene transcript levels, according to the neuroblast cell line considered.
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PMID:Retinoic acid and forskolin activate the human MDR1 gene promoter in differentiated neuroblasts. 797

When treated in vitro with retinoic acid, many neuroblastoma cell lines undergo neuronal differentiation and show a significant increase in human multi-drug resistance gene (MDRI) transcript levels. To determine whether over-expression of the gene may result from activation of its promoter by differentiating agents, the activity of the human MDRI proximal promoter (MDRI pp) transfected to 2 neuroblastoma lines treated with retinoic acid and forskolin was first measured using transient expression assays. The MDRI gene transcript levels of these 2 lines were then measured by Northern blots. The results indicate that retinoic acid and forskolin were able to activate the human MDRI pp in a dose-dependent manner after transfection of the MDRI pp-CAT constructs in the 2 cell models tested, i.e., SK-N-SH and IGR-N-91, a new human neuroblastoma cell line. A significant increase in MDRI gene transcript levels was observed upon treatment with differentiation inducers in SK-N-SH but not in IGR-N-91 neuroblasts. These results suggest that the induction of the MDRI gene promoter is necessary but not sufficient to lead to an increase in MDRI gene transcript levels, according to the neuroblast cell line considered.
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PMID:Activation of the human MDR1 gene promoter in differentiated neuroblasts. 810 11

We investigated the cis-acting sequences involved in the expression of the human aldolase C gene by transient transfections into human neuroblastoma cells (SKNBE). We demonstrate that 420 bp of the 5'-flanking DNA direct at high efficiency the transcription of the CAT reporter gene. A deletion between -420 bp and -164 bp causes a 60% decrease of CAT activity. Gel shift and DNase I footprinting analyses revealed four protected elements: A, B, C and D. Competition analyses indicate that Sp1 or factors sharing a similar sequence specificity bind to elements A and B, but not to elements C and D. Sequence analysis shows a half palindromic ERE motif (GGTCA), in elements B and D. Region D binds a transactivating factor which appears also essential to stabilize the initiation complex.
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PMID:Cis-acting elements in the promoter region of the human aldolase C gene. 834 72

MHC class I molecules are coexpressed with beta 2-microglobulin (beta 2-M) on many somatic cells. However, these proteins are normally not present on cells of the central nervous system (CNS). Cells derived from human neuroblastomas were used as a model for investigating the molecular basis for the paucity of MHC class I and beta 2-M gene expression in neural cells and for the induction of these genes by two cytokines, IFN-gamma, and TNF-alpha. These cytokines independently increased MHC class I and beta 2-M cell surface expression on the neuroblastoma cell lines. IFN-gamma or TNF-alpha also increased MHC class I and beta 2-M steady-state RNA levels and the expression of MHC class I and beta 2-M CAT reporter constructs transiently transfected into the neuroblastoma cell lines, indicating that the cytokines acted by increasing the transcription of these genes. MHC class I and beta 2-M genes share two conserved regulatory elements, an NF kappa B-like site and the IFN consensus sequence, that act as a constitutive enhancer and an IFN-responsive element, respectively. Low MHC class I and beta 2-M gene expression in these cells was accounted for by undetectable to low factor binding activity specific for the above regulatory elements of these genes. TNF-alpha increased factor binding activity specific for the NF kappa B-like elements and IFN-gamma increased factor binding activity specific for the IFN consensus sequence elements of the MHC class I and beta 2-M genes, but not vice versa. Taken together, our results indicated that IFN-gamma and TNF-alpha increased MHC class I and beta 2-M gene expression in the neuroblastoma cell lines by inducing factor binding to the regulatory elements present in both genes.
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PMID:Regulation of MHC class I and beta 2-microglobulin gene expression in human neuronal cells. Factor binding to conserved cis-acting regulatory sequences correlates with expression of the genes. 846 72


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