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)

It is well known that interferons inhibit cell growth. However, we found that human interferon-gamma (HuIFN-gamma) enhanced the growth of human osteosarcoma cells, HOS-Y1 cells, in a dose-dependent manner. This enhancing effect was found only under the following conditions: when the cells were precultured for 2 or 3 days and then treated with HuIFN-gamma for 2, 3, or 4 days, and when the cells were seeded at a density of 1,000 or 2,000 cells/well. The degree of enhancement of cell growth was maximum when the cells were precultured at a density of 1,000 cells/well for 3 days and then treated with HuIFN-gamma for 2 days. The enhancing effect of HuIFN-gamma disappeared in the presence of anti-HuIFN-gamma antibody. In addition, it was found that the conditioned medium from HOS-Y1 cells enhanced the growth of HOS-Y1 cells, and that the conditioned medium from HOS-Y1 cells cultured with HuIFN-gamma enhanced the cell growth more than that from cells cultured without HuIFN-gamma. Epidermal growth factor (EGF), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta 1(TGF-beta 1) did not enhance the growth of HOS-Y1 cells. These results suggest that HuIFN-gamma enhanced the cell growth by augmenting the production of unknown growth factor(s) in HOS-Y1 cells via an autocrine mechanism.
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PMID:Enhancement of the growth of human osteosarcoma cells by human interferon-gamma. 147 55

Class I and class II major histocompatibility complex (MHC) gene products are key recognition units in the induction and regulation of the immune response. Expression of class I and class II may be constitutive or inducible by cytokines such as interferon-gamma (IFN-gamma). A key step in the induction of MHC genes is recognition of IFN-gamma by its membrane receptor. The work described here examines the regulation of the occupied IFN-gamma receptor by the cytoskeleton. To do this the authors have used the fungal metabolites dihydrocytochalasin B (DHCB) and cytochalasin D (CD), substances that bind to actin filaments and thereby disrupt the cytoskeleton. The authors have studied the effect of DHCB and CD on IFN-gamma-induced MHC gene expression in 143 B cells, a human osteosarcoma-derived cell line. Herein the authors demonstrate that alterations in the cytoskeleton induced by DHCB and CD can lead to increases in IFN-gamma-induced MHC gene expression. Dihydrocytochalasin B added up to 3 hours after IFN-gamma results in a threefold to sixfold increase in levels of class II mRNA while producing minimal enhancement of class I gene expression. In contrast, glyceraldehyde-3-phosphate dehydrogenase mRNA expression was unaltered by IFN-gamma or by the cytochalasins. The increased amount of class II mRNA can be accounted for by a concomitant increase in transcription rate of this gene. Studies using 125I-IFN-gamma demonstrate that the occupied IFN-gamma receptor associates with a Triton X-100 insoluble fraction of 143 B cells and that DHCB and CD markedly inhibit this association. The results described here provide evidence that is consistent with the hypothesis that the activity of the occupied IFN-gamma receptor may be modulated by interactions with the cytoskeleton of the cell. This receptor may be one of a group of plasma membrane receptors that are sensitive to the action of cytochalasins after ligand binding.
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PMID:Hyperexpression of interferon-gamma-induced MHC class II genes associated with reorganization of the cytoskeleton. 190 5

Recombinant human interferon-alpha 2C and recombinant human interferon-gamma (5-1000 U/ml) inhibit the proliferation of normal human bone-derived cells and a human osteosarcoma cell line. In the bone-derived cells the inhibitory effect of interferon-gamma was significantly greater than that of interferon-alpha, whereas in the osteosarcoma cell line the inhibitory effects of both interferons were quantitatively similar. Interferon-alpha did not affect the alkaline phosphatase activity of either type of cells. In contrast, interferon-gamma affected the activity of the enzyme in both cell types: in the bone-derived cells the effect of interferon-gamma was stimulatory whereas in the osteosarcoma cells the effect was inhibitory. In both cell types interferon-gamma selectively inhibited the incorporation of radiolabelled proline into type I collagen. In the osteosarcoma cells, the effects of both interferons on collagen synthesis were quantitatively similar. In the bone-derived cells, however, interferon-alpha decreased proline incorporation into collagen and non-collagen proteins to a similar extent and thus did not affect collagen synthesis when expressed as a percentage of total protein synthesis. Two-dimensional polyacrylamide gel electrophoresis of the radiolabelled proteins of the cell layer synthesised by both cell types in the presence of either interferon demonstrated that this treatment enhanced or induced the synthesis of a total of 21 individual proteins (19 in bone cells, 14 in osteosarcoma), ranging in apparent molecular mass over 14-87 kDa. The set of proteins induced was different in all four combinations of cells and interferon. A tentative identification of several of the proteins was possible based upon estimation of molecular mass, preferential induction by interferon-alpha or interferon-gamma and differential induction in normal and transformed bone-derived cells. The results of this study demonstrate that interferons have complex effects upon the proliferative and biosynthetic activities of human bone-derived cells and demonstrate significant differences between the responses of normal cells and transformed bone-derived cell line. Further investigations will be required in order to determine whether or not these differences are unique to the osteosarcoma cell line or are a characteristic of the effects of interferons on bone-derived cells in general.
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PMID:Interferons and bone. A comparison of the effects of interferon-alpha and interferon-gamma in cultures of human bone-derived cells and an osteosarcoma cell line. 212 83

Tumor necrosis factor-alpha (TNF alpha) and interferon-gamma (IFN gamma) have potent effects on bone resorption and collagen synthesis in cultured rat long bones. Since the effects of TNF alpha and IFN gamma may result from interaction with multiple cell types, we studied the effects of these cytokines on the synthesis of DNA and collagen in one cell type with osteoblast phenotype, cloned rat osteosarcoma cells (ROS 17/2.8). Recombinant human TNF alpha did not affect DNA synthesis after 48 h with concentrations of 10(-11)-10(-8) M and inhibited DNA synthesis slightly at 10(-6) M. Recombinant rat IFN gamma (5-500 U/ml) caused a dose-dependent inhibition of DNA synthesis. Coincubation with TNF alpha and IFN gamma inhibited DNA synthesis more than maximal doses of either cytokine alone. This enhanced inhibitory effect was due to the induction of a response to TNF alpha by IFN gamma, since preexposure of cells to IFN gamma for 24 h, followed by incubation with TNF alpha alone for an additional 48 h, also resulted in increased inhibition of DNA synthesis. Preexposure to TNF alpha for 24 h, followed by IFN gamma alone, did not increase the inhibition of DNA synthesis. Incubation with either IFN gamma (5-500 U/ml) or TNF alpha (10(-10)-10(-6) M) inhibited the incorporation of [3H]proline into collagen. Coincubation with intermediate concentrations of both cytokines resulted in an inhibitory effect greater than that produced by maximal concentrations of either alone. The results indicate that 1) IFN gamma and TNF alpha have direct actions on osteoblast-like cells in vitro; 2) IFN gamma modulates the DNA response to TNF alpha; and 3) the greater responses to combined cytokines than to high doses of either alone suggest that these cytokines act, at least in part, through different pathways.
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PMID:Inhibitory effects of tumor necrosis factor-alpha and interferon-gamma on deoxyribonucleic acid and collagen synthesis by rat osteosarcoma cells (ROS 17/2.8). 249 7

The antitumor effect of human natural and recombinant interferon-gamma (IFN-gamma) was evaluated in human osteosarcomas grown as xenografts in nude mice. IFN-gamma was given as daily subcutaneous injections, alone or in combination with IFN-alpha. The growth of two out of three tested osteosarcomas was inhibited by 2 x 10(5) IU of natural IFN-gamma. A five times higher dose of recombinant IFN-gamma, as compared with natural (n) IFN-gamma, was needed to obtain growth inhibition of one osteosarcoma. This difference in dose-response could be explained by differences in pharmacokinetics. Hence, subcutaneously administered natural IFN-gamma gave 10 times higher serum levels than obtained with the recombinant type. Combination treatment with IFN-alpha and IFN-gamma induced a potentiation of the antitumor effect in one osteosarcoma. In another osteosarcoma, 2-4 x 10(5) IU of nIFN-gamma did not effect tumor growth and could not potentiate the antitumor effect of 2-4 x 10(5) IU of nIFN-alpha. By using DNA analysis in cell suspension and tissue section, the proportion of aneuploid tumor cells within the xenograft could be estimated. This analysis showed that the antitumor effects of IFN were more pronounced than mere measurement of tumor volume suggested. IFN-inhibited tumors were partly replaced by fibroblasts or bone tissue. In conclusion, at the doses given nIFN-gamma appeared to have similar antitumor effects as IFN-alpha in two osteosarcomas, whereas one was sensitive to only IFN-alpha. Combination IFN treatment induced a potentiation of the antitumor effect in one osteosarcoma but not in another. The differences between the osteosarcomas in obtained antitumor effect of IFN treatment probably reflects individual IFN sensitivity and demonstrates the importance of assessing several tumors of the same neoplastic entity.
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PMID:Effect of human interferon-alpha and interferon-gamma on growth, histology, and DNA content of human osteosarcomas in nude mice. 250 87

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

Induction by interferon-gamma of indoleamine 2,3-dioxygenase (a tryptophan degradation enzyme) was examined with 11 human cell lines. The enzyme induction was demonstrated in 7 of the 11 cell lines. The induced enzyme in each of the 7 cell lines was identical to the enzyme purified from human placenta, as evidenced by immunoblot analysis with a monoclonal antibody specific to the placental one. The extent of the induction varied largely with the cell line; a relatively high induction was observed with HEL (lung fibroblasts), NY (osteosarcoma), and A-431 (epidermoid carcinoma). The enzyme induction was dependent on the concentration of interferon-gamma and occurred 12-18 h after addition of interferon-gamma to the cultures. Interferon-alpha or -beta was completely ineffective in this induction. Interferon-gamma inhibited the growth of the 7 cell lines observed with the enzyme induction, and this growth inhibition was accompanied with a complete deletion of tryptophan (less than 1 microM) in the culture medium by the induction of the enzyme. For two of these cell lines, the inhibition was partially reversed by an addition of exogenous tryptophan to the medium not to be depleted. These findings indicated that the growth inhibition by interferon-gamma was in part explained by the tryptophan depletion in the medium caused by the enzyme induction.
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PMID:Mechanism of interferon-gamma action. Characterization of indoleamine 2,3-dioxygenase in cultured human cells induced by interferon-gamma and evaluation of the enzyme-mediated tryptophan degradation in its anticellular activity. 312 85

Osteoclast-mediated bone resorption plays a crucial role in osseous remodeling. Osteoblasts are important regulators of this activity, in part through their ability to produce osteoclast-regulating soluble factors such as interleukin-6 (IL-6). IL-11 is a newly appreciated pleotropic cytokine whose spectrum of biological activities overlaps with that of IL-6. As a result, we hypothesized that osteoblasts are an important skeletal source of this cytokine. To test this hypothesis, we characterized the IL-11 production of unstimulated and stimulated SaOS-2 human osteosarcoma cells. Unstimulated cells produced modest amounts of IL-11. The osteotropic agents recombinant IL-1 (0.25-5 ng/ml), transforming growth factor-beta 1 (0.1-10 ng/ml), PTH (10(-8)-10(-11) M), and PTH-related peptide ((10(-8)-10-11 M) further increased SaOS-2 cell IL-11 protein production and messenger RNA accumulation. These stimulatory effects were dose and time dependent, and the IL-11 that was produced was bioactive, as demonstrated by its ability to stimulate the proliferation of T10D plasmacytoma cells. The protein kinase-C activator, 12-O-Tetra-decanoylphorbol 13-acetate, and a variety of cAMP agonists [forskolin, prostaglandin E1, prostaglandin E2, and (Bu)2AMP] also stimulated osteoblast IL-11 protein production and messenger RNA accumulation. In contrast, recombinant IL-4, recombinant interferon-gamma, and endotoxin did not stimulate SaOS-2 cells in a similar fashion. Importantly, the ability to produce IL-11 was not a unique property of SaOS-2 cells, because primary human trabecular bone osteoblasts also produced significant amounts of bioactive IL-11 when stimulated with transforming growth factor-beta 1. These studies demonstrate that appropriately stimulated human osteoblasts and osteoblast-like cells are potent producers of IL-11 and suggest that osteoblast-derived IL-11 may be an important component of the cytokine network mediating osteoblast-osteoclast communication in normal and pathological bone remodeling.
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PMID:Cytokine and hormonal stimulation of human osteosarcoma interleukin-11 production. 783 81

The in vitro interactions between human osteosarcoma (HOS) cells and platelets were studied in real time using video-enhanced microscopy. Interference reflection techniques showed that platelets were lysed within minutes after contacting HOS cells that had been treated with interferon-gamma. Untreated HOS cells lysed platelets less efficiently. Platelet lysis depended on platelet-tumor cell contact and on extracellular Ca2+. A number of possible mechanisms were excluded. Lysis of platelets in proximity to tumor cells can provide these with growth factors and thereby contribute to the metastasis-enhancing effect of platelets.
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PMID:Lysis of blood platelets by human osteosarcoma cells in vitro. 799 61

We investigated the expression of cytokine transcripts in osteoblast-like cells derived from explants of pagetic and normal bone. A reverse transcription-linked PCR was used that allowed the simultaneous analysis of a range of cytokines. Normal osteoblast-like cells were found to contain the transcripts for IL-1 beta, IL-6, and TGF-beta 1. For the first time we detected in bone cells the two other mammalian isoforms of TGF-beta, beta 2, and beta 3. Furthermore, we have also identified mRNA for IL-3 and the novel chemotactic factor, IL-8. Using this sensitive technique it was not possible to detect mRNA for IL-1 alpha, IL-2, IL-4, IL-5, IL-7, TNF-alpha, or interferon-gamma. The human osteosarcoma cell line Saos-2 also showed a similar pattern of expression of these cytokines to primary osteoblast-like cells, with the exception that TNF-alpha was also identified. Cells isolated from pagetic bone showed essentially the same profile of cytokine expression as normal bone except that TNF-alpha was also detected in two of four samples. The cytokine profile of successive populations of cells harvested from one explant culture at 9, 22, and 57 days showed a consistent pattern of cytokine expression, demonstrating the phenotypic stability of the osteoblast-like cells in long-term cultures.
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PMID:PCR detection of cytokines in normal human and pagetic osteoblast-like cells. 825 52


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