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)

The cytotoxic action of prostaglandin (PG) D2, E1 and F2 alpha was examined on human neuroblastoma cells (NB-1 cell line), and PGD2 was found to be the most effective. PGE1, thought to be the most effective among all PGs in the therapy of neuroblastoma, was much less effective than PGD2. PGF2 alpha did not show any inhibitory effect on the proliferation of NB-1 cells. When PGD2 was added, the cytoplasma became microscopically larger, then the cells gradually died off. PGD2 also exerted a dose-dependent inhibition of DNA and RNA syntheses. These results strongly suggest an antineoplastic activity of PGD2 for human neuroblastoma.
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PMID:Prostaglandin D2 inhibits the proliferation of human neuroblastoma cells. 657 53

Combination of dibutyryl adenosine 3', 5'-cyclic monophosphate or prostaglandin E1 (PGE1) and papaverine effectively induced differentiation of neuroblastoma in mice. Two cases of human neuroblastoma with stage III and IV were administered intraaortic PGE1 infusion combined with oral papaverine and conventional chemotherapy. There were no noticeable side effects and the treatment was effective in decreasing tumor size and promoting tumor maturation in the infused area. However, distant osseous metastases were developed in both cases, during and after the PGE1 administration. They survived 30 and 17 months, respectively, from the initiation of therapy. (Jpn J Cancer Chemother 10(9): 1936-1943, 1983) These results prompted us to study the metastatic potentials of neuroblastoma. In vitro studies demonstrated that cultured human neuroblastoma cells (NB-1, GOTO, SK-N-DZ, SJ-N-KP, SJ-N-CG and SK-N-FI) aggregate human platelets with maximum aggregation ranging from 28% to 51%. Addition of PGE1 or PGD2 to PRP effectively inhibited the tumor-cell-platelet interaction, with IC50 approximately 100 nM for PGE1 and 10 nM for PGD2, respectively. In addition, 50 microM PGE1 or PGD2, 5 microM PGI2 reversed neuroblastoma-induced platelet aggregation in 4 out of 5 cell lines were studied. These findings indicate a the possible role of PGs in effective inhibition of neuroblastoma metastases in vivo. However, two cell lines (SK-N-DZ and SJ-N-CG), which had been exposed to 8.5 microM PGE1 or PGD2 for 90 min and 72 hr, respectively, retained the platelet aggregating activity which was not significantly different from that of untreated cells. We conclude that clinical application of intraaortic PGE1 in the treatment of advanced neuroblastoma has advantage in potentiation of tumor cell kill and in inducing maturation. Administered PGE1 may exert its action in two ways: in preventing tumor metastasis or possibly in enhancing the metastatic potential of neuroblastoma cells. Further refinement of these modalities including other PGs such as PGD2 or PGI2 and more detailed studies on optimal PG administration to prevent metastasis should be evaluated in future.
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PMID:[Differentiation induction and potentiation of chemotherapy by PGE1 infusion in patients with neuroblastoma--effect of PGE1 on metastatic potential of neuroblastoma]. 658 82

The characteristics of a new neuroblastoma cell line (MC-NB-1) established from the bone marrow of a 2-year-old male are described. Morphologically, the cells appear as flattened and epithelial-like or as small and spherical. Electron microscopy demonstrated microtubules and dense core secretory granules. The doubling time was approximately 35 hr. Isoenzyme patterns and catecholamine secretion indicated a human line of neuronal origin. The soft agar tumor colony forming system demonstrated drug resistance in vitro comparable to in vivo nonresponsiveness. The stemline karyotype of MC-NB-1 is 44,Y,del(1) (p22:), -4, -7, +del(7)(q22:), -16, +t(7;16)(16pter leads to 16q24::7q22 leads to 7q32), -17. Additionally, double-minute bodies were observed. However, no evidence of homogeneous staining regions (HSRs) were detected.
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PMID:Distinguishing characteristics of a new neuroblastoma cell line. 661 38

To clarify the role of gangliosides in the morphological and biochemical differentiation of neuronal cell cultures, the model cell culture system represented by two neuroblastoma cell lines, GOTO and NB-1, which were established from adrenal gland and metastatic neck lymph node, respectively, was examined. We found that the total ganglioside fraction from human brain had two remarkable effects on these cell lines, which are similar to those of nerve growth factor (NGF): (a) an increase in the cell number, and (b) an increase in the neurite number and the total length of neurites. In these cases, the genuine effector in total gangliosides could not be ascribed to a possibly contaminating NGF-like protein, but rather to a particular molecular species of the gangliosides, GQ1b, which could completely replace the effector function not only qualitatively but also quantitatively. Our results provide direct evidence for the participation of gangliosides in such functions.
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PMID:GQ1b, a bioactive ganglioside that exhibits novel nerve growth factor (NGF)-like activities in the two neuroblastoma cell lines. 661 15

Two isoforms of brain ankyrin, 440 kDa and 220 kDa ankyrinB, which are products of alternatively spliced pre-mRNA encoded by a single gene, are both expressed in human neuroblastoma NB-1 cells. Expression of the polypeptide and mRNA of the larger isoform increased upon induction of neurite outgrowth in NB-1 cells by dibutyryl cAMP, while those of the smaller isoform were unaffected. The expressed 440 kDa ankyrinB was concentrated at the tip of growing neurites and was partly co-localized with GAP-43. These results suggest that 440 kDa ankyrinB is one of the neuronal growth-associated proteins and provides an interesting example of gene regulation by alternative splicing in neuronal cells.
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PMID:Possible involvement of the 440 kDa isoform of ankyrinB in neuritogenesis in human neuroblastoma NB-1 cells. 780 94

Even though the current limits of treatment for advanced stage neuroblastoma require an understanding of biology and new therapeutic approaches, few invasion models of human neuroblastoma (HNB) which evaluate experimental therapies have been reported. We describe herein a reproducible murine model of cranial invasion after the intraocular xenograft of HNB in congenitally athymic mice. Approximately 10 weeks after the intraocular injection of 5 x 10(6) NB-1 HNB cells, 70% (14/20) of the mice developed intracranial invasion with skull involvement. There was no operative mortality. Macroscopically, deformities of the cranium were revealed in all 14 mice, 5 of which developed exophthalmos. Microscopically, cranial invasion mainly involved the extradural space, skull, and orbita; however, brain involvement could not be seen, indicating that the dura may act as a barrier. These invasive characteristics are very similar to those seen in humans; thus, we believe that this model provides a useful tool for evaluating the biology of, and new therapeutic approaches against, cranial invasion of neuroblastoma in vivo.
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PMID:A cranial invasion model of human neuroblastoma using congenitally athymic mice. 791 35

The neuropeptide vasoactive intestinal polypeptide (VIP) has a broad range of functions, and its expression has been correlated with neuronal differentiation. Here we present data on the effects of retinoic acid (RA), a known modulator of neuronal differentiation, on VIP gene expression in the human neuroblastoma cell line NB-1. Morphological data, surprisingly, indicate that these cells are not differentiated concomitant with the increase in VIP gene expression. RA was found to exert a concentration-dependent induction of peptides derived from the VIP precursor molecule, prepro-VIP. The effect at both the messenger RNA (mRNA) level, evaluated by Northern blots, and the peptide level, measured by RIAs, was found to be slow and long lasting. No changes in the processing of prepro-VIP were observed using gel chromatography and RIAs specific for various prepro-VIP sequences. Also, the expression of mRNA for the prohormone-processing enzyme PC2, present in these cells, was not altered by RA. The lag period preceding the increase in VIP mRNA led to experiments with the translational inhibitor cycloheximide showing an indirect effect of RA on VIP mRNA expression. Northern blots revealed that at least three mRNAs encoding RA receptor were expressed and rapidly induced by RA in the cells, thus making them possible candidates for the intermediate protein(s) required from the induction of VIP gene expression.
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PMID:Characterization of the effects of retinoic acid on vasoactive intestinal polypeptide gene expression in neuroblastoma cells. 792 7

The neuroblastoma cell line NB-1 is induced to start neurite outgrowth by dibutyryl cyclic AMP (Bt2cAMP). To study the function of Alzheimer amyloid protein precursor (APP), a stable cell line overexpressing APP was established by cDNA transfection. The APP cDNA was driven by the cytomegalovirus early gene promoter. The transformant underwent degeneration as well as neurite outgrowth in the presence of Bt2cAMP, which also increased the amount of APP mRNA and protein. The expressed APP was mainly processed in the secretory pathway and few amyloidogenic fragments were observed. Hence, not only the beta/A4 protein but also the overexpressed APP itself might be neurotoxic.
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PMID:The toxic effect of Alzheimer amyloid protein precursor overexpressed in the neuroblastoma cell line NB-1 on neurite outgrowth. 792 67

Heat-induced expression of 72-kDa heat shock protein (HSP72) was investigated in a panel of neuronal and non-neuronal cell lines by immunoblotting and immunocytochemistry using monoclonal antibodies directed to HSP72. By immunoblotting, HSP72 expression was observed in most cell lines of mouse (SN6.1b, CL8c4.7, NSC34.6, B2A, C2C12), rat (PC12, C-6, L3), and human (NB-1, GOTO, IMR-32, HeLa) origin under the heat-stressed condition. The mouse neuroblastoma cell line N18TG2, however, did not express HSP72 under the heat-stressed condition. By immunocytochemistry, HSP72 was undetectable in the heat-stressed N18TG2 cells, while it was identified in the heat-stressed SN6.1b cells, a clonal hybrid neuron between N18TG2 and mouse septal cholinergic neuron. By exposure to a priming sublethal heat shock, SN6.1b cells but not N18TG2 cells acquired a significant level of tolerance to a subsequent lethal heat shock. These results suggest that heat-induced expression of HSP72 may contribute to acquisition of the thermotolerant state in SN6.1b cells.
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PMID:HSP72 induction by heat stress is not universal in mammalian neural cell lines. 814 2

Brain-specific isoforms of ankyrin, 440 kDa and 220 kDa ankyrinB, which are generated from a single gene by alternative splicing of pre-mRNA, are both expressed in human neuroblastoma NB-1 cells and the expression of the larger isoform is increased upon induction of neurite outgrowth. Exposure to methylmercury, a potent neurotoxic substance, at a sublethal dose induced dramatic retraction of neurites in NB-1 cells. Concomitantly, synthesis of 440 kDa ankyrinB polypeptide and mRNA were selectively attenuated in methylmercury-treated cells, while the 220 kDa isoform was not affected. These results indicate that the expression of 440 kDa ankyrinB is intimately associated not only with the neurite outgrowth but also with neurite retraction in neuronal cells, and is regulated at mRNA level.
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PMID:Selective down-regulation of 440 kDa ankyrinB associated with neurite retraction. 874 59


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