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)

Ferritin is an iron-containing protein which is a normal component of serum. The levels of ferritin are increased in the sera of some children with neuroblastoma, and this increase appears to be a potent indicator of prognosis. To determine whether synthesis of ferritin by the tumor cells contributes to these increased serum levels, we examined incorporation of radiolabeled leucine by CHP 126, a neuroblastoma derived cell line, into ferritin. Using sequential immunoprecipitation and gel electrophoresis of sonicates from cells maintained in medium containing iron in amounts standard for tissue culture, incorporation of label into ferritin was 0.04% of that into total protein synthesized over the same time period. Addition of up to 40 micrograms of iron as ferric ammonium citrate increased ferritin synthesis to a maximum of 0.16% without altering synthesis of total protein. The pattern of iron-induced enhancement in the neuroblastoma cells was similar to that which was seen using Chang liver cells, a cell line well known to be capable of ferritin synthesis. These results confirm that neuroblastoma cells can synthesize ferritin and that synthesis is regulated by exogenous iron.
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PMID:Synthesis of ferritin by neuroblastoma. 238 59

Neuroblastoma cell lines can have very low MHC Ag expression. The cell lines are insensitive to allo-killing by primed CTL, but are sensitive to non-MHC-restricted cytotoxicity. IFN-gamma increased class I expression, but the cells remained insensitive to CTL. Susceptibility to nonrestricted effectors was preserved. Class I+ glioma cell lines behaved similarly. The CTL resistance was localized to the recognition phase. Neuroblastoma lines did not form conjugates with primed T cells, but were lysed if they were coupled to the effectors via lectins. The levels of class I expression, and resistance to CTL, were constant over a range of IFN doses. HLA-A,B,C structure and distribution were studied more intensively on one cell line, CHP-100. HLA-A2 and -A3 were present on greater than or equal to 99% of the cells, in a unimodal distribution. After IFN treatment, the levels were similar to B cell controls. In two-dimensional gel electrophoresis, the molecules co-migrated with those of B cell controls. The defect may thus be in accessory proteins that are necessary for T cell recognition or binding, rather than in the structure or distribution of the HLA-A,B,C proteins.
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PMID:IFN-treated neuroblastoma cell lines remain resistant to T cell-mediated allo-killing, and susceptible to non-MHC-restricted cytotoxicity. 245 35

Deferoxamine previously has been shown to have potent activity in vitro against human neuroblastoma cells, activity that results from its ability to chelate iron. To further understand the mechanism of deferoxamine-induced cytotoxicity, we looked at its effects on cell cycling and on DNA, RNA, and protein synthesis by CHP 126, a cell line that is derived from tumor tissue of a patient with a neuroblastoma and that is known to be drug sensitive. After 24 hours of exposure to 60 mumol/L deferoxamine, there was a 35% increase in the percent of cells in the nonproliferating and prereplicative phases of the cell cycle and a corresponding decrease in the percent of cells in the DNA synthesis, postreplicative, and mitotic phases of the cell cycle, results that are consistent with a block of cell cycle progression at the early DNA synthesis phase. The inhibitory effects of deferoxamine on DNA synthesis were confirmed by demonstration of a 60% decrease in thymidine incorporation into DNA in short-term cultures of CHP 126. Effects on RNA and protein synthesis were minimal. Equivalent effects on growth were seen by using several chelators that interact with different iron pools, suggesting that both intracellular and extracellular iron are required for growth of neuroblastoma cells.
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PMID:Mechanism of antineuroblastoma activity of deferoxamine in vitro. 245 79

The cytidine analog 5-AZA-2'-deoxycytidine (5-AZA-CdR) has been demonstrated to induce cellular differentiation; on the other hand, induction of differentiation has been suggested as a possible form of therapy for leukemic cells. We have evaluated the possibility that the neuroblastoma malignant tumor growth could be controlled by treatment that promotes the differentiation of immature tumor cells. We have previously reported on differentiation of murine neuroblastoma cells (41A3) treated with 5-AZA-CdR. In this paper, we describe the effect of 5-AZA-CdR on human neuroblastoma cell line CHP-100. The drug-treated cells show some degree of differentiation, demonstrated by morphological and biochemical markers. A significant DNA hypomethylation and partial inhibition of DNA synthesis and cell proliferation is also observed. This effect is more stable than that caused by another cytidine analog, Cytosine-beta-D-Arabinofuranoside (ARA-C).
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PMID:Effect of cytidine analogs on cell growth and differentiation on a human neuroblastoma line. 247 28

Recently m-131-iodobenzylguanidine (MIBG) has been successfully used to image neurocrest-derived tumours such as neuroblastoma. In fact, our autoradiographic evidences demonstrate that MIBG is able to bind, accumulate and be released by neuroblastoma cell line CHP 100 "in vitro", as well as by surgical biopsies from tumours bearing children. Moreover, all the cell lines tested "in vitro" were able to bind MIBG: neuroblastoma (WNT, CHP-100, IMR-32), small cell lung carcinoma (LC-8) and melanoma (WMB). A fibrosarcoma line, despite that it is not neurocrest related, was also able to bind MIBG. However only WNT, CHP-100 and the LC-8 lines were able to accumulate and then release large amounts of MIBG in cytoplasmatic vesicles. The heterogeneity of MIBG uptake "in vitro" seems related to the similar variability observed in the clinical scintigraphies. This phenomenon may be related to the biochemical maturity of individual neuroblastoma tumours.
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PMID:[Intracellular uptake and accumulation of metaiodobenzylguanidine in neuroblastoma cells and small cell carcinoma of the lung]. 254 31

Molecular characterization of two human neuroblastoma cell lines has revealed that both contain multiple homogeneously staining regions (HSRs), each representing a chromosome site of N-myc amplification. The newly established cell line CHP-382/JK had two cytogenetically distinct populations with several identical chromosomal abnormalities, indicating a common progenitor cell. Each population had one HSR, one on chromosome 5 at q31-34 and the other on chromosome 2 at q31-32. Chromosomal in situ hybridization with the N-myc probe pNb-1 demonstrated that both HSRs contained amplified copies of N-myc. Southern blot analysis confirmed amplification of N-myc sequences in genomic DNA of CHP-382/JK. Chromosomal features of CHP-382/JK shared with other neuroblastoma cell lines were the deletion of 1p and the presence of extra 17q material. In addition, the cells were highly reactive to monoclonal antibody PI 153/3 used to identify human neuroblastoma. CHP-382/JK cells were further characterized as neuronal cells by the expression of neurotoxin-responsive Na+ channels. Another neuroblastoma cell line, CHP-134, contained a single cell population with three HSRs, one in the short arm of each chromosome 7 and one in the long arm of a chromosome 6. All three HSRs contained amplified copies of N-myc as shown by in situ hybridization with the N-myc probe pNb-1. One of the 7p HSRs was acquired during culture of CHP-134 cells, whereas the 2q HSR of CHP-382/JK was lost. Such findings highlight the continued process of N-myc amplification and transposition in vitro. To our knowledge, amplification of N-myc in multiple HSRs has not been documented previously in neuroblastoma cell lines.
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PMID:N-myc amplification in multiple homogeneously staining regions in two human neuroblastomas. 258 23

The relationship between the quantity of silver-stained interphasic nucleolar organizer regions (NORs) and nuclear synthetic activity, caryotype, and growth rate was studied in two established neuroblastoma cell lines (CHP 212 and HTB 10). Statistical analysis of silver-stained NORs revealed four times as many in CHP 212 cells compared with HTB 10 cells. No difference was observed in the ribosomal RNA synthesis between the two cell lines. The caryotype index was 1.2 for CHP 212 and 1.0 for HTB 10 cells. The number of chromosomes carrying NORs and the quantity of ribosomal genes was found to be the same for the two cell lines. Doubling time of CHP 212 cells was 20 hours compared with 54 hours for HTB 10 cells. In CHP 212 cells bindering of cell duplication by serum deprivation induced a progressive lowering (calculated at 48, 72, and 96 hours) of the quantity of silver-stained interphasic NORs. Recovery of duplication by new serum addition induced, after 24 hours, an increase of the quantity of silver-stained interphasic NORs up to control levels. In the light of available data, these results indicate that the quantity of interphasic NORs is strictly correlated only to the growth rate of the cell.
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PMID:Relationship between interphasic nucleolar organizer regions and growth rate in two neuroblastoma cell lines. 270 11

Monoiodinated radioligands of the homologous 36-amino acid peptides, neuropeptide Y (NPY) and peptide YY, were prepared by reverse phase high performance liquid chromatography with isocratic elution. [125I-Tyr1]- and [125I-Tyr36]monoiodoNPY bound equally well to a single class of high affinity binding sites on synaptosomal membranes prepared from porcine hippocampus (Kd = 1.0 X 10(-10) M) whereas iodine substitution in Tyr27, for example, partly interfered with the receptor binding. The receptors on the hippocampal membranes did not distinguish between neuropeptide Y and peptide YY either in their monoiodinated or in their unlabeled forms. Six out of twelve human neuroblastoma cell lines had high affinity binding sites for monoiodinated NPY ranging from 2 to 145 X 10(3) sites per cell. The NPY binding to three of the cell lines, SMS-MSN, SMS-KAN, and CHP-234 was of relatively high affinity (Kd = 1.3 to 6.1 X 10(-10) M), and, as in the hippocampal membranes, the long C-terminal fragment, NPY(13-36)peptide was also a relatively potent ligand for these receptors. Two other neuroblastoma cell lines, MC-IXC and CHP-212, expressed NPY receptors characterized by a lower affinity (Kd = 4.8 and 24.6 X 10(-9) M) and negligible cross-reactivity with the C-terminal fragment. It is concluded that monoiodinated radioligands of the tyrosine-rich neuropeptide Y can be prepared and that receptors for these ligands in two apparently different subtypes are found on a series of human neuroblastoma cell lines.
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PMID:Binding of monoiodinated neuropeptide Y to hippocampal membranes and human neuroblastoma cell lines. 270 30

A colorimetric assay was used to compare the in vitro effects on neuroblastoma cell viability of 3.75-60 microM deferoxamine or 0.125-2 microM doxorubicin alone with those of the two drugs in combination. For each of two human neuroblastoma cell lines (CHP 100 and CHP 126), exposure to each drug individually produced dose-related cytotoxic effects within 3 days. When these cells were simultaneously exposed to both drugs, even at concentrations achievable in vivo, cell death was greater than what could be accounted for by either drug alone. Cytotoxicity was further potentiated to a variable extent when the cells were sequentially exposed to deferoxamine and doxorubicin at 24-hour intervals. Thus, this combination of drugs warrants further study.
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PMID:Enhancement of in vitro activity against neuroblastoma by doxorubicin and deferoxamine. 272 52

Natural killer (NK) cells and NK cell activity were determined in three groups (newly diagnosed [n = 21], on therapy [n = 21], and off therapy [n = 18]) of children with various types of malignant solid tumors and in a control group (n = 26) by means of Leu-7 and Leu-11b monoclonal antibodies and a 4-hour 51Cr-release assay, respectively. The erythroleukemia cell line K562 was used as a target cell. The newly diagnosed group included eight patients with localized disease (Stage I-II), ten with bulky but nonmetastatic disease (Stage III), and three with metastases (Stage IV). The mean percent of NK cell activity in the newly diagnosed group was significantly higher than that of the control group. Children with Stage III tumors at diagnosis had higher mean NK cell function than those with Stage I-II and Stage IV. On therapy patients had significantly fewer NK cells and lower NK cell cytotoxicity than those in the other groups studied. We also studied the following: (1) the in vitro effect of recombinant interferon-alpha (rIFN-alpha) and recombinant interleukin-2 (rIL-2) on NK cell function of peripheral blood lymphocytes (PBL) from children with solid malignancies; and (2) the susceptibility of neuroblastoma-derived (CHP-126 and SKNSH) and rhabdomyosarcoma-derived (A-204) cell lines to NK cell lysis. Both rIFN-alpha and rIL-2 enhanced NK cell activity of PBL from children with malignancies and healthy children against K562 and solid tumor cell lines. The enhancing effect or rIL-2 was greater than that of rIFN-alpha. CHP-126 and SKNSH cell lines were susceptible to NK cell lysis mediated by the PBL of children with neuroblastoma and the control group. The A-204 cell line was less sensitive than K562 to NK cell cytotoxicity. Our results suggest a potential therapeutic role for both cytokines in the treatment of malignant solid tumors of childhood.
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PMID:Natural killer cells in children with malignant solid tumors. Effect of recombinant interferon-alpha and interleukin-2 on natural killer cell function against tumor cell lines. 278 77


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