Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

So far, the role of fibroblasts in inflammatory processes has been underestimated. We have previously shown that stimulation of fibroblasts with viruses or bacteria results in a simultaneous production of several cytokines, including interferon-beta, interleukin (IL) 6 and colony-stimulating factors. We here report that virally infected fibroblasts produce also a chemotactic factor for granulocytes. The activity is inducible not only by measles virus but also by IL 1 beta and the double-stranded RNA poly(rI).poly(rC). This factor, when purified to homogeneity, occurs as a 6-7-kDa protein doublet upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The pure protein is serologically related to a fully characterized granulocyte chemotactic peptide (GCP) from monocytes, designated IL8. Furthermore, the chemotactic factor from fibroblasts has an NH2-terminal sequence identical to that of GCP/IL8, small differences in NH2-terminal processing being observed. Finally, in addition to diploid fibroblasts, the osteosarcoma MG-63 cell line is also a producer of GCP/IL8. It can thus be concluded that GCP/IL8 can be produced by several cell types in response to infection and that fibroblasts can contribute to chemotaxis in inflammation.
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PMID:The chemotactic activity for granulocytes produced by virally infected fibroblasts is identical to monocyte-derived interleukin 8. 266 11

The antitumor activity of recombinant human interferon-gamma (ReIFN-gamma) and recombinant human interferon-beta (ReIFN-beta) against human osteosarcoma G-292 cells was compared in vitro and in vivo. Both IFNs inhibited the growth of G-292 cells cultured in vitro and transplanted into nude mice in vivo. In in vivo experiment, both IFNs injected i.t. were more effective at inhibiting the growth of G-292 cells than systemic administration such as i.v., i.p. or s.c. In comparing the various routes of systemic administration of both IFNs, i.v. injection was slightly more effective. Both IFNs exhibited more significant growth inhibition when they were administered every day for 10 d, as compared with a single or intermittent administrations, suggesting that the antitumor activity of both IFNs was time-dependent. Significant difference was not detected in the in vivo antitumor activity between both IFNs when they were compared on the basis of their antiviral units. However, the time dependency for antitumor effect of ReIFN-beta was more significant than that of ReIFN-gamma. ReIFN-gamma and ReIFN-beta used in combination exhibited synergistic antitumor activity both in vitro and in vivo, though the in vivo synergism of both IFNs was not so effective as that of in vitro: These results indicate that both ReIFN-gamma and ReIFN-beta are effective at inhibiting the growth of human osteosarcoma in vivo.
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PMID:Antitumor effect of human recombinant interferon-gamma and -beta against human osteosarcoma transplanted into nude mice. 310 72

Human fibroblast cultures, when stimulated with interleukin-1 (IL-1) produce a growth factor for B-cell hybridoma and plasmocytoma cell lines. The availability of both a fast-growing and high-producer cell line (MG-63 osteosarcoma cells) and of a highly sensitive and specific assay system for this hybridoma growth factor (HGF) allowed us to obtain analytically pure preparations. Crude HGF from MG-63 cells was processed through a five-step concentration and purification schedule. Sequential adsorption to controlled pore glass (CPG) beads, antibody affinity chromatography and gel filtration resulted in a 10,000-fold purification to a specific activity of 10(9) units/mg HGF. Electrophoretically pure HGF was obtained after additional purification by cation-exchange chromatography and reversed-phase HPLC. The purification procedure revealed two distinct biologically active HGF components. The amino-terminal sequence of one of the two components was determined and found to correspond to that already predicted from cDNA clones of a protein alternatively called 26-kDa protein, interferon-beta 2 (IFN-beta 2) or B-cell stimulating factor-2 (BSF-2). The first two designations (26-kDa protein and IFN-beta 2) refer to a postulated fibroblast secretory protein with so far no unambiguously defined function; the latter designation (BSF-2) refers to a T-cell product possessing differentiation stimulatory effect on B-cell lines. The reported results firmly establish that the protein is secreted by fibroblasts and reveal that it possesses B-cell growth stimulatory activity. The new designation interleukin-6 (IL-6) is proposed to resolve prescribing nomenclature confusion.
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PMID:Purification and characterization of human fibroblast-derived hybridoma growth factor identical to T-cell-derived B-cell stimulatory factor-2 (interleukin-6). 349 18

Cultures of normal diploid fibroblasts and of a human osteosarcoma cell line (MG-63) are shown to be able to produce a factor which promotes the growth of B cell hybridomas (hybridoma growth factor, HGF). The induction is stimulated by treatment of the cells with interleukin 1 (IL 1) (alpha or beta) or polyriboinosinic-polyribocytidylic acid [poly(rI).poly(rC)]. Combined treatment with cycloheximide and actinomycin D also stimulates production and enhances production induced by IL 1 or poly(rI).poly(rC). Extremely small doses of IL 1 (0.1 units/ml) are active as inducer of HGF. Also, under optimal conditions the yield of HGF can attain as much as 10(4) units/ml. Tumor necrosis factor (TNF-alpha), which otherwise shares various properties with IL 1, is a weak inducer of HGF. Although there is a superficial resemblance between induction of HGF and that of interferon-beta, the two activities are serologically distinct and conditions for their induction are quite different. In fact, conditions for induction of HGF are indistinguishable from those described for the induction of the mRNA of the so-called 26-kDa protein (also known as interferon-beta 2). Finally, the HGF derived from IL 1- or poly(rI).poly(rC)-treated fibroblasts is serologically not distinguishable from that produced by mitogen-stimulated peripheral blood leukocytes.
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PMID:Interleukin 1 and poly(rI).poly(rC) induce production of a hybridoma growth factor by human fibroblasts. 354 52

Three human tumor cell lines (one osteosarcoma and two neuroblastoma lines) were assessed for combined interferon-beta (IFN-beta)/chemotherapeutic drug antigrowth effect under in vitro conditions. Two different methods to measure this effect were used: colony formation in soft agar and counting of cells growing as monolayers. The cells were incubated with a chemotherapeutic drug (adriamycin, dacarbazine, actinomycin D, cis-platinum, methotrexate, VP-16-213, or vincristine) at relevant concentrations for 1 h, washed twice, and incubated with IFN-beta in concentrations ranging from 100 to 1000 IU for continuous exposure. All combinations resulted in an additive or synergistic combination effect with one exception: methotrexate/IFN-beta in the monolayer method after 1 week, a combination which was additive after 3 weeks however. The combinations VP-16-213/IFN-beta and cis-platinum/IFN-beta produced the most pronounced synergistic effects. A statistical evaluation of the null hypothesis for additivity was done. These results provide a rationale for designing clinical studies combining IFN-beta with current chemotherapeutic drugs.
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PMID:The combined effect of interferon-beta and cytostatic drugs on human tumor cell lines in vitro. 386 99

We have studied the appearance of human interferon-beta (HuIFN-beta) as well as its mRNA in cells treated with a protein, 22K factor, isolated from the culture supernatant of mitogen-stimulated human peripheral blood leukocytes. By itself 22K was found to be unable to induce production of significant amounts of HuIFN-beta protein. However, when aided by treatment with cycloheximide or cycloheximide and actinomycin D (superinduction), 22K caused increases in production ranging from 3- to 20-fold, depending on the cells (diploid or MG-63 osteosarcoma) and the induction schedule. Cells treated with 22K alone produced small amounts of HuIFN-beta mRNA, which was only detectable with a highly sensitive method. In combination with cycloheximide, 22K induced levels of mRNA detectable with less sensitive methods as well. These experiments provide further support for the concept that the antiviral activity of 22K is mediated by its ability to stimulate transcription of the HuIFN-beta gene in cells.
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PMID:Stimulation of fibroblast interferon production by a 22K protein from human leukocytes. 398 Nov 35

After infection with Sendai virus or Newcastle disease virus (NDV) strain F, human osteosarcoma MG63 cells produced large amounts of interferon-beta. Both interferon production and overall protein synthesis were strongly inhibited by hypertonic salt. Interferon mRNA synthesis, however, was little affected by hypertonic salt up to twice normal salt concentrations, although cellular RNA synthesis was inhibited under these conditions. The results are compared to those obtained with polyriboinosinic acid: polyribocytidylic acid copolymer [poly(rI) . poly(rC)] inductions of MG63 cells.
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PMID:The effect of hypertonic salt on interferon and interferon mRNA synthesis in human MG63 cells. 617 28

The promotive effects of poly-cations on immunoglobulin production was investigated using human-human hybridoma cells. Among poly-cations tested, epsilon-poly-L-lysine with hydrochloride (approximately 4 kDa), which has been used as an antibacterial food additive, had the greatest activity in enhancing IgM production of human-human hybridoma HB4C5 cells without stimulating cell proliferation. Immunoglobulin production stimulatory (IPS) activity of epsilon-poly-lysine was not affected by trypsin digestion. It was stable below 60 degrees C but completely inactivated with heating at 100 degrees C for 30 min. epsilon-Poly-lysine also enhanced interferon-beta (IFN-beta) production of human osteosarcoma MG-63 cells, but this stimulatory effect was reduced by the trypsin digestion.
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PMID:Enhancement of production of IgM and interferon-beta in human cell lines by poly-lysine. 853 72

The purine nucleoside analogs fludarabine, 2-chlorodeoxyadenosine, and 2'-deoxycoformycin exhibit impressive activity in lymphoproliferative malignancies of adults and children. Their mechanism of action is not clear. Studies have suggested that their use is associated with significant myelosuppression, immunosuppression, and in some circumstances, increased infection with viral and opportunistic pathogens. Because interferons (IFNs) are known to have immunomodulatory activity as well as potent antiproliferative and antiviral activity, we examined whether the chemotherapeutic purine nucleoside analogs alter interferon-beta (IFN-B) gene expression in MG63 in human osteosarcoma cells. Northern blot analysis showed a dose-dependent inhibition of IFN-B mRNA accumulation in response to a known inducer (Poly I-Poly C) all three purine analogs. Hybridization analysis also revealed that inhibition of IFN-beta mRNA accumulation by the purine analogs is not a result of decreased mRNA stability. Further analysis of gene expression by PCR differential display indicated that the effect of the purine analogs was restricted to only a limited number of inducible genes. The data suggest that these molecules alter the signaling process involved in regulating the expression of specific genes, including IFN-beta. These findings predict that the use of purine nucleoside analogs may reduce IFN production in vivo and thereby abrogate host defenses against infectious pathogens.
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PMID:Chemotherapeutic purine analogs alter the level of interferon-beta mRNA induced by poly I-poly C in cultured osteosarcoma cells. 918 62

PRDI-BF1, the human ortholog of mouse Blimp-1, is a DNA-binding protein involved in postinduction repression of interferon-beta gene transcription in response to viral infection. PRDI-BF1 also has an essential function in driving terminal differentiation of B lymphocytes and therein silences multiple genes. Here we show PRDI-BF1 assembles silent chromatin over the interferon-beta promoter in the osteosarcoma cell line U2OS through recruitment of the histone H3 lysine methyltransferase G9a. G9a is recruited only when in a complex with PRDI-BF1. G9a catalytic activity is required for the accumulation of methylated histone H3 and transcriptional silencing mediated by PRDI-BF1 in vivo. This establishes a mechanism for the recruitment of G9a, the main mammalian euchromatic methyltransferase, and defines nonembryonic targets of G9a.
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PMID:PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing. 1498 9


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