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

Human immunodeficiency virus (HIV) infection of brain macrophages and astroglial proliferation are central features of HIV-induced central nervous system (CNS) disorders. These observations suggest that glial cellular interactions participate in disease. In an experimental system to examine this process, we found that cocultures of HIV-infected monocytes and astroglia release high levels of cytokines and arachidonate metabolites leading to neuronotoxicity. HIV-1ADA-infected monocytes cocultured with human glia (astrocytoma, neuroglia, and primary human astrocytes) synthesized tumor necrosis factor (TNF-alpha) and interleukin 1 beta (IL-1 beta) as assayed by coupled reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and biological activity. The cytokine induction was selective, cell specific, and associated with induction of arachidonic acid metabolites. TNF-beta, IL-1 alpha, IL-6, interferon alpha (IFN-alpha), and IFN-gamma were not produced. Leukotriene B4, leukotriene D4, lipoxin A4, and platelet-activating factor were detected in large amounts after high-performance liquid chromatography separation and correlated with cytokine activity. Specific inhibitors of the arachidonic cascade markedly diminished the cytokine response suggesting regulatory relationships between these factors. Cocultures of HIV-infected monocytes and neuroblastoma or endothelial cells, or HIV-infected monocyte fluids, sucrose gradient-concentrated viral particles, and paraformaldehyde-fixed or freeze-thawed HIV-infected monocytes placed onto astroglia failed to induce cytokines and neuronotoxins. This demonstrated that viable monocyte-astroglia interactions were required for the cell reactions. The addition of actinomycin D or cycloheximide to the HIV-infected monocytes before coculture reduced, > 2.5-fold, the levels of TNF-alpha. These results, taken together, suggest that the neuronotoxicity associated with HIV central nervous system disorders is mediated, in part, through cytokines and arachidonic acid metabolites, produced during cell-to-cell interactions between HIV-infected brain macrophages and astrocytes.
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PMID:Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease. 146 Apr 27

The induction of human immunodeficiency virus type 1 (HIV-1) gene expression by cytokines was investigated in cells of central nervous system origin. These were human neuroblastoma, glioblastoma, and astrocytoma cell lines, a murine oligodendroglioma and primary murine astrocyte cultures. The cytokines used were tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), IL-6, and interferons alpha and gamma (IFN alpha, gamma). Transient transfection of cells with a chloramphenicol acetyltransferase (CAT) reporter gene under the control of the HIV-1 long terminal repeat (LTR) showed significant augmentation following treatment by particular cytokines. TNF alpha was found to augment HIV LTR-directed CAT activity in all cell types. IL-1 beta also activated the HIV LTR reporter gene in glioblastoma, astrocytoma, and astrocyte cells. IL-6 enhanced HIV gene expression in one example only, the primary astrocyte cultures. The interferons generally suppressed expression from the LTR except IFN gamma which produced a twofold rise in the murine glial cells and IFN alpha augmenting expression in one neuroblastoma cell line. No synergy was observed between pairs of activating cytokines tested. The HIV tat gene product was found to be functional in all cells, cotransfection of a tat expression vector transactivating expression from the LTR, with varying degrees of efficiency. In some cell lines the combination of an activating cytokine and tat resulted in an enhancement above that obtained by cotransfection of tat alone. In others, the level of CAT activity did not significantly change. Analysis of nuclear extracts from cytokine-treated cells further implicated the involvement of NFKB in the induction of HIV-1 gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine augmentation of HIV-1 LTR-driven gene expression in neural cells. 159 55

We report the expression of different interleukins (IL) in four human glioblastoma and neuroblastoma cell lines. The glioblastoma cell line LI, expresses IL-1 beta and IL-6 mRNA, though not IL-2 and IL-4. The expression of the former gene is modulated by retinoic acid. Two cell clones [BE(2)-C and BE(2)-M17] as well as the neuroblastoma cell line SK-N-BE(2), from which both clones were derived, express IL-6 mRNA, but not IL-1 beta, IL-2 or IL-4. Both IL-1 beta and IL-6 cytokines are known to increase hypothalamic CRH mRNA, a gene reported to be expressed in all these cell lines. The production of both cytokines and neuropeptides indicates a complex dialogue between tumour cells and anti-tumour immunity.
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PMID:Interleukin-1 beta and interleukin-6 mRNA are expressed in human glioblastoma and neuroblastoma cells respectively. 160 28

Expression of the lymphokine genes in human astroglial cell lineage was studied. Primers for 9 different human lymphokines, from IL-1 alpha to IL-8, were used to analyze RNA transcripts in 5 cultured human astrocytoma, one neuroblastoma cell line and 4 fresh brain specimens by polymerase chain reaction (PCR). mRNA transcripts of neither IL-1 nor IL-3, the biological activities of which were observed in rat primary cultured astrocytes, could be detected within these cell lines. Two out of 5 unstimulated astrocytomas, U138 and U373, expressed IL-6 genes. IL-8 gene was detected within U87, U138, U251, U373 glioma cells. After stimulation with IL-1 beta, all astrocytoma and one neuroblastoma cell line expressed IL-6 and IL-8 genes. In addition to the cultured cells, we examined IL-6 and IL-8 gene expression within human malignant astrocytoma specimens. The result shows that three out of four glioma specimens expressed IL-6 and IL-8 genes. From these results, it is suspected that astroglial cell-derived IL-6 or IL-8 may participate in local immune reactions accompanying infection, degeneration and malignancies in the central nervous system.
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PMID:[An analysis of lymphokine gene expression within astrocytoma]. 163 May 67

We have previously reported on stimulation of clonal growth of cell lines from human solid tumors by recombinant human interleukin 3, recombinant human granulocyte-macrophage colony-stimulating factor, and recombinant human granulocyte colony-stimulating factor (W. E. Berdel et al., Blood, 73: 80-83, 1989; Exp. Hematol., 16: 510, 1988). Within an extensive screening program of hematopoietic growth factor activity on malignant cells, the effects of recombinant human interleukin 6 (rhIL-6) were tested on the growth (tritiated thymidine uptake and human tumor cloning assay) of 26 different human cell lines derived from a wide range of solid tumors (head and neck, 4; lung, 1; pancreatic, 1; gastric, 1; colorectal, 3; renal, 3; bladder, 1; prostate, 1; breast, 2; ovary, 2; choriocarcinoma, 1; sarcoma, 2; glioblastoma, 2; neuroblastoma, 2). rhIL-6 (dose range up to 10(4) IU/ml) caused no reproducible enhancement or inhibition of tritiated thymidine uptake by tumor cell lines from nonhematopoietic origin. Furthermore, 19 of the tumor cell lines were clonogenic in a capillary modification of the human tumor cloning assay. No reproducible stimulation of clonal growth by rhIL-6 was observed in any of the cells tested. Particularly, there was no sensitivity of those cell lines for rhIL-6, which were previously shown to be sensitive for recombinant human interleukin 3 and recombinant human granulocyte-macrophage colony-stimulating factor in this assay. On the other hand, there were no significant growth-inhibitory effects of rhIL-6 on the cell lines tested in this study. Further experiments showed no influence of neutralizing monoclonal anti-hIL-6 antibody on the growth of 3 kidney carcinoma cell lines, making autocrine growth-modulating loops for IL-6 in these lines unlikely. In conclusion, no major interactions between hIL-6 and the growth of the human malignant cell lines from nonhematopoietic origin tested were detected in this study.
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PMID:Studies on the interaction between interleukin 6 and human malignant nonhematopoietic cell lines. 185 4

Expansion of the natural killer (NK) subset of lymphocytes represents a rare leukemia phenotype with variations in clinical presentation, morphology, surface phenotype, and effector function. This paper reports on a 5-year-old male patient who had an unusual presentation of an NK cell leukemia that was initially diagnosed as neuroblastoma. A bone marrow (BM) aspirate showed clumps of undifferentiated cells with the following phenotype: CD56bright+, CD33dim+, CD45-, CD2-, CD19-, CD16-, and CD57-. Cytochemistry was noncontributory. The patient, having failed to respond to conventional neuroblastoma chemotherapy, was subsequently diagnosed as having NK cell leukemia based on functional in vitro assays. The patient responded to acute lymphoblastic leukemia (ALL) chemotherapy but relapsed 4 weeks into treatment and eventually died 25 weeks after initial presentation. The cell surface phenotype observed is consistent with a rare NK cell subset, the biology of which has not been well defined. Freshly isolated BM cells killed K562 cells in a conventional 51Cr-release assay. Both interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) induced LAK activity against the Daudi cell line. IL-2 induced proliferation of the leukemic cells. TNF-alpha, IFN-gamma, IL-6, IL-1ra, and TGF-beta levels were assessed and found to be concentrated in BM, in contrast to plasma samples. TNF-alpha was present at a high concentration in BM (150.9 pg/ml), probably a reflection of the associated disease pathology of severe bone pain and pyrexia. In summary, this paper details clinical and laboratory investigations of a leukemia of a rare NK cell subset.
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PMID:Recognition of unusual presentation of natural killer cell leukemia. 757 92

Metastasis in children with neuroblastoma (NB) is a poor prognostic factor despite intensive therapy. In the near future, stem cell factor (SCF) is likely to be used clinically to accelerate bone marrow (BM) recovery after high-dose chemotherapy in patients with advanced NB. The high frequency of BM metastases in NB could be secondary to BM-derived human growth factors (HGF) modulating the adhesion, secondary growth (or both) of circulating metastatic NB cells. To test this hypothesis, we studied the in vitro effects on NB cell lines grown in chemically defined medium of SCF, interleukin (IL)-1 beta, IL-3, IL-6, basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF-beta) used alone or in combination. The antigenic expression of NB-associated cell adhesion molecules (CAM) HLA class 1, intercellular CAM-1, neural-CAM and CD44 were assayed by monoclonal antibodies and flow cytometry, and DNA synthesis by 3H-thymidine uptake. The expression of CAM was not modulated by SCF or other HGFs. An increase in thymidine uptake was induced by bFGF alone in IMR-32 cells, while SCF and other HGFs had no notable effect. Our results indicate that SCF and other BM-derived HGFs are unlikely to have a generalised effect on the expression of adhesion molecules by NB cells or proliferation. The clinical administration of recombinant human SCF to children with NB should be safe.
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PMID:Effects of stem cell factor and other bone marrow-derived growth factors on the expression of adhesion molecules and proliferation of human neuroblastoma cells. 757 47

Genetically engineered monocytes and macrophages may have potential as effector cells for the adoptive immunotherapy of cancer. As a first step, we have transfected the genes encoding either mouse interferon (IFN)-gamma, human interleukin (IL)-6, mouse IL-4, or mouse tumor necrosis factor (TNF)-alpha into the mouse macrophage cell line, J774A.1 cells using retroviral vectors. In vitro activation of J774A.1 cells by gene modification was assessed by morphological changes, proliferative activity was determined by [3H]-TdR uptake, and cytolytic activity was assessed using an 18-hour chromium-51 (51Cr) release assay. In vivo tumoricidal activity was studied by means of local adoptive immunotherapy using intratumoral injection of transfected effector cells. IFN-gamma gene-transfected J774A.1 [J7(IFN-gamma)] cells developed filamentous processes, increased doubling times, and enhanced tumoricidal activity against three tumor cell lines: the TNF-sensitive fibrosarcoma line WEHI 164 and the TNF-alpha-resistant cell lines B16 melanoma and C1300 neuroblastoma. IL-6-, TNF-alpha-, and IL-4-gene-transfected J774A.1 cells also had augmented tumoricidal activity but did not display any changes in morphology or growth. Cytolytic activity was markedly reduced after the addition of anti-TNF-alpha antibodies. Cytolytic J7(IFN-gamma) cells showed upregulated expression of TNF-alpha messenger RNA. After intratumoral injection of J7(IL-4) and J7(IFN-gamma) cell mixtures, 50% of established B16 melanomas were rejected by C57BL/6 mice, thereby demonstrating synergistic killing. Further studies on gene-transfected macrophages should better define their potential usefulness in tumor immunotherapy.
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PMID:Increased in vitro and in vivo tumoricidal activity of a macrophage cell line genetically engineered to express IFN-gamma, IL-4, IL-6, or TNF-alpha. 762 Dec 59

Data from the literature demonstrate the existence of a growing family of neuropoietic cytokines; members of this group have structural motifs in common with other members and with neurotrophic factors. In this research we studied the responses elicited in vitro by some of these molecules in two different neuronal populations: murine neuroblastoma N18TG2 and neurons from chicken dorsal root ganglia. Both IL-2 and IL-6 improve the survival of murine neuroblastoma cells in clonal density plating experiments; in addition IL-2 significantly inhibits thymidine incorporation by single cell suspension. The survival of sensory neurons, on the other hand, non-responsive to IL-2 and IL-6, was significantly supported by IL-3, which also stimulates their morphological differentiation, inducing the formation of a well-developed neural net. In conclusion, results reported here confirm the neurotrophic activity of some ILs and provide additional neuronal models for future investigations.
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PMID:Enhanced survival and differentiation in vitro of different neuronal populations by some interleukins. 779 10

The cell line AG-F was isolated from the marrow of a neuroblastoma patient undergoing myeloablative treatment and autologous bone marrow rescue. A year later, the patient developed a Hodgkin's type lymphoma. AG-F cell line demonstrated an unusual phenotype, lacking surface CD2 and CD3, but expressing high levels of CD4, CD5, CD7, CD29, and CD45RO. Markers associated with Hodgkin's lymphoma cells, CD15 and CD30, were also positive. AG-F cells grow in suspension in clusters of 50-200 cells, with a doubling time of 9 h. They can also grow in serum-free medium and form tumors in nude mice. AG-F cells have amplified N-myc and c-myc and high levels of the corresponding mRNA transcripts. Cytogenetic analysis revealed a DNA index by flow cytometry of near tetraploid cells and a karyotype of 85-87 chromosomes, with consistent abnormalities in chromosomes 1, 5, and 9. Gene rearrangement studies revealed rearrangement of the beta gene of the T-cell receptor. AG-F cells secrete high levels of IL-6, IL-8, IL-10, and GM-CSF. Cell adherence and formation of long processes could be induced by fibronectin and were enhanced by exposure to PMA. Cells exposed to phorbol myristate acetate (PMA) had increased expression of CD11a, CD11b, CD18, CD45RO, and HLA-DR, whereas expression of CD15 and CD30 was markedly decreased. Similarly, the level of c-myc and N-myc oncoproteins and the levels of the cytoskeletal proteins, actin, tubulin, and vimentin markedly decreased early after PMA-induced differentiation.
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PMID:Isolation and characterization of an early T-helper/inducer cell line with a unique pattern of surface phenotype, constitutive cytokine secretion and myc oncogene expression. 825 4


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