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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vital staining of neuroblastoma cells with acridine orange produces a bright intracellular red-orange fluorescence most probably due to the occurrence of RNA. The distribution of this fluorescence depends on the state of morphological differentiation. The fluorescence is predominantly found in the perikaryon, the growth cones, and the endings of the processes of differentiated cells. This is of special interest in respect to the biochemistry of differentiation and the function of nerve cells. Comparative autoradiographical studies with 3H-uridine demonstrate that the newly synthesised RNA is transported into the endings of the cell processes.
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PMID:Distribution of acridine orange-stained RNA in neuroblastoma cells during differentiation. 7 Jul 60

The purpose of the present study was to examine the distribution pattern of acridine orange (AO) chromatin interaction products (AOCI) in human neuroblastoma IMR-32 cells and to test whether AO labeling is correlated with BrdU incorporation, and immunohistochemical localization of DNA polymerase alpha, and human N-myc-gene product. Effects of aphidicolin, alpha-amanitin, and actinomycin D on visualization of AO binding to euchromatin and on N-myc-gene expression were also examined. About 25% of the cell nuclei in logarithmic growth phase were immunohistochemically demonstrated to be labeled with BrdU after incubation at 37 degrees for 30 min, indicating cells in DNA synthesis. Most of the cell nuclei showed positive immunoreactivity to DNA polymerase alpha, while human N-myc gene product was found in about 60-80% of the cell nuclei. Electron microscopic studies revealed that about 25% of neuroblastoma cells showed characteristic AOCI within cell nuclei. In the presence of aphidicolin, alpha-amanitin, and actinomycin D, positive cells for N-myc gene product decreased markedly. Percentages of AO positive cells and numbers of AOCI per cell nucleus also showed a marked decrease. But northern blot analysis demonstrated that the expression level of N-myc gene was only repressed by the transcriptional inhibitors alpha-amanitin and actinomycin D. However, no repression was caused by aphidicolin. The present and previous studies of the authors suggest that the ultracytochemical AO method may be indicative for conformational changes of chromatin of cells confined to the cell cycle. Inhibitors of RNA and DNA synthesis then may change the conformational state of chromatin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Electron microscopic localization of acridine orange binding to euchromatin in human neuroblastoma cells. 190 67

The established cell line NB6 (human neuroblastoma) was perturbed in vitro, in order to evaluate the disdifferentiation mechanism of malignant neoplastic cells during cultivation. The methods for perturbation were as follows: 1) 50%-cell removal from dishes; 2) 0.1 mg/ml of vincristine (VCR) contact; and 3) 10Gy of beta-radiation. Specimens were harvested every 24 hours until 72 hours, simultaneously stained for DNA and RNA with acridine orange (AO), and cell kinetically analyzed for DNA/RNA/cell-distribution with the aid of flow cytometry (FCM). Thus disdifferentiated cells and/or newly cell cycle traversing cells, were evaluated. The new subpopulations were considered to be recruited from G1A and/or Gq (Darzynkieowicz et al.) into the cell cycle after perturbations. Cells of the new subpopulations had smaller volume compared with the control cells. Furthermore, in the current study, newly cell cycle traversing cells of NB6 appeared to have a disturbed cell cycle traverse in G2B phase from the clonological changing patterns of FCM cytograms. These new subpopulations were revealed to be able to passage up to five or six times. Though it was impossible to make them appear, these new cycling subpopulations might be capable of remaining as permanent clones in vitro.
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PMID:[Cell kinetic analysis with flow cytometry as a disdifferentiation mechanism in human neuroblastoma cells in vitro]. 273 77

The nature of red fluorescent particles in vitally acridine orange stained C 1300 neuroblastoma monolayer cells was evaluated by electron microscopy, cytofluorometry, cytopharmacological and cell fractionation studies. At the ultrastructural level the distribution of red fluorescent granules correlated with that of the Golgi complex and Golgi derived structures during various stages of differentiation, mitosis, and under colcemid treatment. Cytopharmacological studies revealed that red fluorescence was displaced in a concentration and time dependent manner with the basic drugs chloroquine and quinacrine. Subcellular fractionation studies showed that acridine orange was concentrated in fractions that also contained the highest amount of acid phosphatase and electron dense vesicles. Vital acridine orange staining of neuroblastoma cells in culture can give information on the relationship between Golgi-derived vesicles and cell functions like proliferation and differentiation. The influence of drugs on these processes can be studied.
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PMID:Further studies on the nature of red fluorescent structures in neuroblastoma monolayer cells vitally stained with acridine orange. 615 46

Six novel alkaloids that contain a fused tetracyclic pyrido[2,3,4-kl]acridine ring system were purified recently from the Red Sea purple tunicate Eudistoma sp. Evaluation of the effects of these alkaloids on cultured neuroblastoma and fibroblast cells revealed that they possess potent growth regulatory properties, and affect cell shape and adhesion. In mouse neuroblastoma cells, the Eudistoma alkaloids inhibited cell proliferation and induced a process of differentiation during which the cells flattened onto the surface, increased considerably in size, and extended long neurites. In hamster fibroblasts the alkaloids slowed down cell multiplication, and caused an exceptional cell flattening or elongation. In a virus-transformed derivative of the hamster fibroblasts the alkaloids restored many aspects of normal cell growth and morphology. In addition, several of the alkaloids mimicked the effects of cAMP analogs on two well-characterized cAMP-mediated processes involved in hepatic glucose metabolism--inhibition of pyruvate kinase (PK) activity and induction of mRNA for phosphoenolpyruvate carboxykinase (PEPCK). All these effects suggest that the Eudistoma alkaloids may act on the cAMP signaling system. However, a single application of these compounds was sufficient to completely block cell multiplication and to induce and sustain differentiation and "reverse transformation". Furthermore, these effects were not readily reversible following removal of the drugs. In contrast, a single application of agents that mimic or elevate cAMP induced a transient response that waned with time in culture, and the effects induced by constant elevation of cAMP reverse rapidly following drug removal. We propose that the Eudistoma alkaloids cause growth inhibition, differentiation, and reverse transformation by modifying the activity state of proteins that are involved in the regulation of cell shape and adhesion and serve as a target for the cAMP and/or other second messenger systems.
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PMID:Novel marine alkaloids from the tunicate Eudistoma sp. are potent regulators of cellular growth and differentiation and affect cAMP-mediated processes. 825 59

Previous studies have established that a number of Nile blue derivatives are potent photosensitizers and that they are localized primarily in the lysosomes. The present study examines whether the lysosome is a main target of the photocytotoxic action mediated by these sensitizers. Chosen for this study were NBS-6I and sat-NBS, which represented, respectively, derivatives with high and moderate degrees of lysosomal. This is indicated by the light-and drug-dose-dependent losses of acid phosphatase staining particles, reduction of hexosaminidase in the lysosome-containing subcellular fraction, and impairment of the lysosomes to take up and sequester acridine orange. Ultrastructurally, swollen and ruptured lysosomes were seen as one of the first evidences of cell damage mediated by these photosensitizers. However, the study also showed that sat-NBS, which is less lysosomal selective, was less effective in mediating lysosomal destruction. Also, the degree of lysosomal destruction mediated by sat-NBS did not parallel the degree of cytotoxicity generated. This implies that for derivatives that are not exclusively localized in the lysosome, other subcellular sites may also be damaged by the photodynamic action and may play a role in the photocytotoxic process.
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PMID:Photodynamic destruction of lysosomes mediated by Nile blue photosensitizers. 837 36

In hippocampal neurons of ground squirrels and neuroblastoma culture the ribosome state was analyzed by staining with acridine orange (AO), labeling with radioactive amino acids, and electron microscopy. Electron microscopy indicated that the extent to which ribosomes associated in polysomes varied from 25% in brain cells of torpid ground squirrels up to 93% in growing neuroblastoma cells. In control rat neurons, it was 75%. The fluorescence of the AO-rRNA complex in ribosomes changed with the polysome/monosome ratio. The red fluorescence of AO-single-stranded rRNA complex as well as ribosome association in polysomes decreased greatly as a function of the shift from polysomes to monosomes. The green fluorescence of AO intercalated in the double-stranded rRNA changed insignificantly. As a result, the ratio of red to green fluorescence intensity, Kalpha, changed more than 3-fold with the changing polysome/monosome ratio. Protein labeling also showed strong positive correlation with Kalpha. Thus, rRNA showed different accessibility for AO binding in active and inactive ribosomes. A possible mechanism of partial rRNA shielding with proteins is proposed. AO fluorescence in the cytoplasm, i.e., AO binding to rRNA in ribosomes, is presumed to reflect adequately the profound changes in the state of cell protein synthesizing system that can be regulated by both functional activity and stress factors.
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PMID:Acridine orange as an indicator of the cytoplasmic ribosome state. 938 38

Programmed cell death or apoptosis is a physiological process that plays an important role during development and maintains tissue homeostasis during adult life. In pathological conditions, such as cancer, apoptosis may be the mechanism by which cancer proliferation is hampered. Many antineoplastic drugs act by inducing apoptosis. SH-SY5Y human neuroblastoma cells undergo apoptosis when exposed to cisplatin, an effective antineoplastic drug. The occurrence of cell death by the apoptotic process is evidenced by the typical electrophoretic laddering of DNA, which begins 24 h after cisplatin exposure and becomes even more apparent at 3-4 days after exposure. Concomitantly, ultrastructural changes of the nucleus and nucleolar organization occur, followed by nuclear membrane disruption and, finally, by cytoplasm degeneration. These last two aspects are present in cultured cells detached from the substrate and predominate in long-term cultures after drug exposure. Confocal laser scanning microscopy (CLSM) of orange-acridine stained nuclei also clearly demonstrates the fragmentation of the chromatin into 3-5 domains. The CLSM, therefore can clearly demonstrate the occurrence of apoptosis in a much simpler, but equally accurate way than electron microscopy.
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PMID:Ultrastructural and confocal laser scanning microscopical aspects of apoptosis in cultured human neuroblastoma SH-SY5Y cells. 1132 25

Prion diseases are characterized by an accumulation of PrP(Sc), a misfolded isoform of the normal cellular prion protein, PrP(C). We previously reported the bioactivity of acridine-based compounds against PrP(Sc) replication in scrapie-infected neuroblastoma cells and now report the improved potency of bis-acridine compounds. Bis-acridines are characterized by a dimeric motif, comprising two acridine heterocycles tethered by a linker. A library of bis-(6-chloro-2-methoxy-acridin-9-yl) and bis-(7-chloro-2-methoxy-benzo[b][1,5]naphthyridin-10-yl) analogs was synthesized to explore the effect of structurally diverse linkers on PrP(Sc) replication in scrapie-infected neuroblastoma cells. Structure-activity analysis revealed that linker length and structure are important determinants for inhibition of prion replication in cultured scrapied cells. Three bis-acridine analogs, (6-chloro-2-methoxy-acridin-9-yl)-(3-[4-[3-(6-chloro-2-methoxy-acridin-9-ylamino)-propyl]-piperazin-1-yl]-propyl)-amine, N,N'-bis-(6-chloro-2-methoxy-acridin-9-yl)-1,8-diamino-3,6-dioxaoctane, and (1-[[4-(6-chloro-2-methoxy-acridin-9-ylamino)-butyl]-[3-(6-chloro-2-methoxy-acridin-9-ylamino)-propyl]-carbamoyl]-ethyl)-carbamic acid tert-butyl ester, showed half-maximal inhibition of PrP(Sc) formation at 40, 25, and 30 nM, respectively, and were not cytotoxic to uninfected neuroblastoma cells at concentrations of 500 nM. Our data suggest that bis-acridine analogs may provide a potent alternative to the acridine-based compound quinacrine, which is currently under clinical evaluation for the treatment of prion disease.
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PMID:Potent inhibition of scrapie prion replication in cultured cells by bis-acridines. 1262 50

Recent evidence indicates that methyl jasmonate, a plant stress hormone, exhibits anticancer activity on human cancer cells. Whether methyl jasmonate could inhibit the growth of human neuroblastoma cells still, however, remains largely unknown. In this study, administration of methyl jasmonate to cultured neuroblastoma cell lines, SK-N-SH and BE(2)-C, resulted in a decrease of cell viability in a dose-dependent and time-dependent manner as demonstrated by MTT colorimetry and colony formation assay. The results from RT-PCR indicated that the expression of proliferating cell nuclear antigen, but not of cyclin D1, was downregulated by methyl jasmonate. Accordingly, the cell cycle of methyl jasmonate-treated neuroblastoma cells was arrested at the G0/G1 phase. Moreover, incubation of SK-N-SH and BE(2)-C cells with methyl jasmonate resulted in characteristic changes of apoptosis, as demonstrated by acridine orange-ethidium bromide (AO/EB) staining, Hoechst 33258 staining and flow cytometry. Moreover, methyl jasmonate decreased the expression of the X-linked inhibitor of apoptosis protein and survivin, critical members of the inhibitors of apoptosis protein family, in neuroblastoma cells. These findings indicate that methyl jasmonate suppresses the growth of cultured human neuroblastoma cells associated with downregulation of proliferating cell nuclear antigen, and induces apoptosis accompanied by downregulation of the X-linked inhibitor of apoptosis protein and survivin, which lays the groundwork for further investigation into the mechanisms of methyl jasmonate-mediated anticancer activities.
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PMID:Methyl jasmonate downregulates expression of proliferating cell nuclear antigen and induces apoptosis in human neuroblastoma cell lines. 1852 16


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