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)

1. Neuroblastoma (NB) is an unusual neuroectodermal tumor showing a high degree of spontaneous regression. NB cells can be induced to differentiate in vitro by various agents. Cell differentiation results in morphological changes characteristic of the mature neuronal phenotype, including outgrowth of neurite-like structures with several interconnections. 2. Recent experiments indicate that morphological differentiation of NB cells is associated with changes in expression of N-myc, c-myc, and c-myb oncogenes and synthesis of neurofilament proteins. However, little is known about the transcription of neurofilament genes during differentiation. 3. We have analyzed the expression of both the N-myc oncogene and mid-size neurofilament (NF) genes in the LAN-1 human NB cell line, cultured in the presence of retinoic acid (RA). Continuous treatment with RA induced morphological differentiation within 5-6 days. The transcription of N-myc was down-modulated within 24 hr of the initial exposure to RA. The mid-size NF mRNA was increased at this time. The expression of N-myc was not modified in serum-deprived LAN-1 cells, indicating that N-myc transcription is unaffected by the arrest of the cells in the G1 phase. 4. We conclude that new synthesis of mid-size NF mRNA and a decrease in N-myc transcription precede de novo formation of neurite-like processes and morphological cell differentiation of neuroblastoma cells.
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PMID:Different regulation of mid-size neurofilament and N-myc mRNA expression during neuroblastoma cell differentiation induced by retinoic acid. 212 47

Phosphatidylinositol (PI) turnover has recently been implicated in the regulation of cell proliferation and transformation. We have investigated its role in differentiation using LAN-1 cells, a human neuroblastoma cell line that can be induced to differentiate along the neuronal pathway by retinoic acid (RA). We have found that treatment of LAN-1 cells with RA is followed by a rapid decrease of inositol phospholipid metabolism, using myo-[1,2-3H]inositol or [1(3)-3H]glycerol. No changes were observed in both [3H]inositol and [3H]glycerol uptake within 24 h of RA treatment. Decreased incorporation of the metabolic precursor into PI 4-monophosphate and PI 4,5-bisphosphate occurred within 1 h of RA treatment. No changes were seen in the specific radioactivity of the precursor pools up to 1 h of treatment with RA. Analysis of labeled PI metabolites from prelabeled cells indicated a rapid decrease of inositol 1,4,5-trisphosphate and 1,2-diacylglycerol content within 1 min of induction of LAN-1 cell differentiation. These findings constitute the earliest reported events in neuroblastoma cell differentiation.
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PMID:Retinoic acid rapidly decreases phosphatidylinositol turnover during neuroblastoma cell differentiation. 215 53

The immunomagnetic depletion method for removing tumor cells from bone marrow, previously refined using a Burkitt lymphoma model, was tested with neuroblastoma cells. The efficiency of depletion was quantified by immunofluorescence with a detection limit of 3.3 log of cell depletion corresponding to the elimination of 99.84% of an initial tumor cell content of 10%. A panel of five monoclonal antibodies (UJ13A; UJ127.11; UJ181.4; alpha-Thy1; H11) purged 2.8 log of SKNBE and LAN-1 cells, while two of these antibodies as single agents allowed only for a 1.7 log (UJ13A) and a 1.7 to 2.0 log (alpha-Thy1) depletion. This underlines the advantage of an antibody panel for neuroblastoma purging. The new antibody S-L 11.14, an IgG2a against small cell lung cancer which recognizes 90% of neuroblastoma cells purged 2.8 log.
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PMID:[Evaluation of a modified immunomagnetic procedure for the purging of neuroblastoma cells from bone marrow]. 219 50

Cell lines from 26 human cancers were studied for cytotoxicity when treated with normal pregnancy serum. Cytotoxicity manifested by cell death and cytolysis, occurred in 4 of 8 neuroblastomas studied: SK-N-SH, NGP, LAN-5, and IMR-32. In NGP and SK-N-SH, evidence is presented showing that the cytotoxicity resulted from the cell-surface binding of a natural IgM 'antibody', which sensitized the neuroblastoma cells to the lytic action of complement (C). This system may be involved in a cytolytic form of spontaneous regression of neuroblastoma.
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PMID:The cytolysis of human neuroblastoma cells by a natural IgM 'antibody'-complement system in pregnancy serum. 229 53

The use of labelled radiopharmaceuticals such as metaiodobenzylguanidine (m-IBG) enables neuroblastomas and other malignant cells from neural crests to be visualized. In vitro study of cellular incorporation into human neuroblastoma lines (SK-N-SH, SK-N-MC, LAN I) showed that only the SK-N-SH line retained iodine-125 m-IBG (125I-m-IBG) significantly. Fifty-five percent of the initial activity was retained after 1 hr incubation at a concentration of 10(-7) M of m-IBG (specific activity: 1,480 MBq/mg). Beyond this value, m-IBG uptake mechanisms were saturated. Study of release kinetics showed a rapid first phase (50% released after 4 hr) and a slower second phase (30% of the value retained at the equilibrium point was present after 48 hr), indicating the existence of a storage compartment. Autoradiography studies confirmed the intracytoplasmic localization of m-IBG and showed that a low percentage (3 to 5%) of SK-N-SH cells strongly retained m-IBG. Cytotoxicity tests showed that SK-N-SH cell growth was significantly reduced during the first days of culture, following 2 hr incubation with 1,500 KBq of 125I-m-IBG, whereas no toxic effect on SK-N-MC cells was found at the same activity. Moreover, the toxic effect observed in the SK-N-SH line was clearly related to the use of 125I-m-IBG since the same activity of 1,500 KBq of non-coupled 125I was without effect. For the latter line, colony-forming capacity was reduced for activities of 150 and 1,500 KBq of 125I-m-IBG, with respectively 32% and 38% lower survival rates. The cytotoxic effect of labelled m-IBG was, however, limited in non-saturating concentrations because the specific activity used was too low. Moreover, the low number of cells reconcentrating m-IBG is indicative of the heterogeneous cellular composition of the SK-N-SH line.
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PMID:In vitro therapeutic targeting of neuroblastomas using 125I-labelled meta-iodobenzylguanidine. 235 89

We describe an in vitro method which is useful for purging autologous bone marrow of neuroblastoma cells. The method utilizes a single murine monoclonal antibody 3G6 (an immunoglobulin MK) which we have previously developed against the ganglioside GD2; undiluted human complement; and unfractionated whole bone marrow at 1 X 10(7) nucleated cells/ml. Tumor cell clonogenic assays, Hoechst 33342 fluorescent nuclear stain, and trypan blue viability stain methods were used to assay cytotoxicity. This complement-mediated cytotoxicity technique killed 99.9-100% of neuroblastoma cell lines NMB-7, LAN-1, LAN-5, and IMR-6, while normal marrow precursor cells were not detectably damaged. The presence of normal bone marrow did not inhibit the human complement-mediated cytotoxicity. Applying the cytotoxicity method to whole unseparated bone marrow demonstrated killing of seeded neuroblastoma cells, with no gross hemolysis or cell clumping. The method did not require expensive special equipment, use of animal complement sera, or prior fractionation of the bone marrow. The average marrow nucleated cell recovery was 95%. These studies indicate that in vitro purging of autologous marrow infiltrated with neuroblastoma with monoclonal antibody 3G6 and human complement is both technically feasible and effective in eradicating residual tumor while preserving bone marrow stem cells.
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PMID:Eradication of neuroblastoma cells in vitro by monoclonal antibody and human complement: method for purging autologous bone marrow. 241 4

The turnover of phosphatidylinositol (PI) is believed to constitute a crucial step in the signaling pathways for stimulation of cells by a variety of bioactive substances, including differentiating agents; however decisive evidence for the idea has not been obtained. In the present paper, we investigated the involvement of PI turnover in cell differentiation using a human neuroblastoma cell line, LAN-1, which can be induced to differentiate along the neuronal pathway by both retinoic acid (RA) and gamma-interferon (gamma-IFN). Analysis of labelled phosphatidylinositol metabolites from prelabelled cells indicated a rapid decrease of inositol 1,4,5-trisphosphate and 1,2-diacylglycerol within 1 min of induction of LAN-1 cell differentiation by RA, while no changes were observed in gamma-IFN-treated cells. These findings indicate the occurrence of decreased inositol phospholipid turnover in RA-treated LAN-1 cells and suggest that phosphoinositide-derived metabolites may not constitute general regulators of cellular differentiation.
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PMID:Phosphatidylinositol turnover is not a general regulator of neuroblastoma cell differentiation: comparison between two differentiating agents, retinoic acid and gamma-interferon. 249 54

The effects of gamma-interferon (gamma-IFN) on the growth, morphology, and phenotypic expression of the human neuroblastoma (NB) cell line, LAN-1, have been extensively tested. Low doses of gamma-IFN allowing more than 90% cell viability induce morphological differentiation and growth inhibition. Cells exposed to gamma-IFN significantly decreased their growth rate, became smaller and poligonal, and sprouted long cellular processes with varicosities along their course, typical of the neurites seen in differentiated NB cells; morphological changes appeared within 48 h of culture with 1,000 U/ml gamma-IFN. The new morphological aspect reached the maximum expression after 6 days of culture, becoming more evident when fresh drug was added after 2 days of culture. A decrease in [3H]thymidine incorporation was also observed within 24 h; cell growth was completely inhibited at the 6th day. Membrane immunofluorescence showed several changes in NB-specific antigen expression after 6 days of treatment with gamma-IFN. At the same time gamma-IFN also modulated cytoskeletal proteins. These findings suggest that noncytotoxic doses of gamma-IFN do promote the differentiation of LAN-1 neuroblastoma cells which is associated with the reduced expression of the malignant phenotype.
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PMID:Effects of gamma-interferon on the growth, morphology, and membrane and cytoskeletal proteins expression of Lan-1 cells. 251 15

The microtubule associated protein called tau, found primarily in neurons, was detected in a human neuroblastoma cell line, LAN-5. Cells treated with retinoic acid (2.0 x 10(-5) M) differentiate and acquire processes similar to neurons. Differentiated and logarithmically growing undifferentiated cells were exposed to varying doses of doxorubicin (an anthracycline chemotherapeutic antibiotic). While doxorubicin was lethal to many undifferentiated dividing cells, it was not as damaging to differentiated cells. After 2 to 4 days of doxorubicin treatment, the cells were harvested, the protein concentration determined and SDS-PAGE performed. Proteins were blotted onto nitrocellulose paper and immunostained with either a rabbit antiserum or mouse monoclonal antibody to tau. Undifferentiated LAN-5 cells treated with 4.0 x 10(-8) M doxorubicin for 4 days and cells treated with 8.0 x 10(-8) M doxorubicin for 2 days displayed a distinct lower band (just below the 50 kd marker) that was either absent or very faint in untreated controls.
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PMID:Doxorubicin affects tau protein metabolism in human neuroblastoma cells. 251 86

A panel of 8 new Mabs have been produced against neuroblastoma cells (LAN-1) previously treated with IFN-gamma. All selected Mabs from 2 different fusions have been shown to detect epitopes on the GD2 ganglioside molecules highly expressed on all cells of neural crest origin including neuroblastoma, glioblastoma and melanoma. Our results imply that modulation of GD2 exposure on NB cells is dependent on culture conditions and moreover that IFN-gamma increases the surface expression of GD2 and thereby enhances their immunogenicity.
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PMID:Monoclonal antibodies to gamma-interferon treated LAN-1 cells detect modulation of ganglioside GD2 exposure on human neuroblastoma cells. 251 14


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