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)

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

Interferon-alpha is currently under evaluation as an antineoplastic agent in several types of tumour. Despite its clear in vitro effects, the effectiveness of interferon in vivo is limited. To assess whether this discrepancy reflects pharmacokinetic limitations, the authors analysed interferon distribution in 2 osteosarcoma patients by scintigraphy using 123I-interferon-alpha-2a. Numerical analysis of the scintigraphic records demonstrated that the main organs of elimination were the kidneys, when the calculation was made on the basis of surface area. On the other hand, the apparent total uptake by liver (whose projection surface--i.e. the area exposed to the lens--is greater) was higher, reaching about 25 to 30% of the injected dose. The projection surface of the tumour was able to take up radiolabelled interferon in both cases, resulting in a 4-fold increase in the external radiation count compared with the equivalent region of the contralateral limb (although it is not possible to determine whether the label is present on the tumour itself or on the surrounding inflammatory cells). Thus, interferon-alpha seems able to reach at least the immediate neighbourhood of osteosarcoma mass.
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PMID:Scintigraphic study of radiolabelled interferon-alpha in osteosarcoma patients. 231 32

Three human tumor cell lines derived from an osteosarcoma (OHA cells), a bladder carcinoma (EJ cells), and a gastric sarcoma (SHAC cells) were passaged serially in the presence of human interferon-alpha (IFN-alpha) for extended periods of time. The long-term IFN-alpha treatment induced a partial reversion of OHA tumor cell phenotype as exemplified by inhibition of cell proliferation, lack of cellular overlapping in confluent cultures and marked reduction in tumorigenicity. In contrast, under the same conditions, long-term IFN treatment did not reverse but even potentiated some of the phenotypic characteristics (including tumorigenicity) of EJ and SHAC cells. In the three tumor cell lines, the transforming ability, genomic level, or expression of activated oncogenes, c-Ki-ras, c-Ha-ras, and N-ras, respectively, were unaltered with long-term IFN-alpha treatment. Our data indicate that IFN-induced phenotypic changes are not necessarily associated with changes in oncogene expression.
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PMID:Interferon-induced phenotypic changes in human tumor cells relative to the effects of interferon on c-ras oncogene expression. 243 60

Xenografts of human osteosarcoma growing in athymic mice are inhibited in growth rate by human interferon-alpha (IFN-alpha) treatment. In addition, differentiation of trabecular bone occurs external to the osteosarcomatous tissue and this is entirely dependent on IFN treatment. We have used species-specific anticollagens and antivimentin antibodies to determine the species origins of this trabecular bone. By using immunohistochemical procedures, it was found that this bone is host-derived. These results suggest that IFN provoked the production of a bone-inducing agent by the human osteosarcomas.
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PMID:Interferon effects on osteoinduction. 248 37

The growth of human osteosarcoma xenografts in nude mice can be inhibited by human interferon-alpha (IFN-alpha). Histologic examination of growth-inhibited tumors has revealed mineralization and partial replacement of the tumor by normal bone tissue. We have investigated whether the normal bone tissue was formed by differentiated tumor cells or by induction of host stroma to differentiate into bone tissue. Employing antibodies to both murine and human type I collagen, it was found that the normal bone produced in IFN-inhibited osteosarcomas was host derived. These results suggest that IFN induced the osteosarcoma cells to produce a bone-inductive agent that interacts with the host cells, and leads to the formation of mature normal bone tissue in a heterotopic site.
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PMID:Interferon-inhibited human osteosarcoma xenografts induce host bone in nude mice. 321 16

The sensitivity of 11 human osteosarcoma xenografts in nude mice to human interferon-alpha (IFN-alpha) was studied. Growth inhibition could be demonstrated in all tumors but the necessary IFN-alpha dose ranged from 1 X 10(5)-1 X 10(6) IU/day. IFN-alpha had to be given daily to attain growth arrest and growth resumed after reduction of the IFN-alpha dose. The xenografts could be divided in two groups based on their sensitivity to IFN-alpha: one group of five xenografts that were growth arrested by IFN-alpha, 2 X 10(5) IU/day, and another group of six xenografts in which this dose was insufficient to arrest growth. The proportions of S-phase cells, determined by DNA flow cytometry of untreated control xenografts, were lower in the former group compared to the latter less IFN-alpha sensitive group. Histological examination revealed that in four of the five more IFN-alpha sensitive xenografts, tumor tissue was replaced by normal bone and marrow tissue. This was not seen in the respective control xenografts and not in any of the six less sensitive IFN-alpha treated xenografts. It appears that less proliferative osteosarcoma xenografts are more sensitive to growth inhibition by IFN-alpha. Interestingly the antitumor effect by IFN-alpha on these xenografts was expressed not only by growth arrest but also by tumor differentiation.
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PMID:Growth inhibition of human osteosarcomas in nude mice by human interferon-alpha: significance of dose and tumor differentiation. 346 89

Of five tested human osteosarcoma xenografts growing in nude mice, two could be growth-arrested by both natural interferon-alpha (nIFN-alpha) and recombinant IFN-alpha 2c (rIFN-alpha 2c). The other three less sensitive xenografts could only be partly growth-inhibited by the nIFN-alpha while no effect was seen with rIFN-alpha 2c. The leukocyte-derived IFN, thus, appeared to have higher antitumor activity per antiviral unit than the recombinant-produced IFN. It is questionable whether this observed difference is of practical relevance for clinical trials employing different IFN-alpha preparations.
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PMID:Comparison of growth inhibiting effect of natural and recombinant interferon-alpha on human osteosarcomas in nude mice. 347 20

Human lymphoblastoid interferon-alpha (IFN-alpha) has been coupled using N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) to a murine monoclonal antibody (791T/36) which reacts with antigens expressed on human osteogenic sarcomas. The purified conjugates retain antibody activity as defined by their capacity to compete with binding of fluorescein isothiocyanate-labelled 791T/36 antibody to 791T cells. IFN-alpha-791T/36 antibody conjugates synthesized with 125I-trace-labelled IFN-alpha and 131I-trace-labelled antibody also bound to 791T cells, but not to bladder carcinoma T24 cells. The conjugates also retain the capacity of free IFN to activate natural killer cells in human peripheral blood lymphocytes and show specific localization in human osteogenic sarcoma xenografts developing in immunodeprived mice. These findings establish that conjugates containing IFN linked to a monoclonal antibody reacting with osteogenic sarcoma-associated antigens have potential for targeted immunotherapy and in related investigations with antibody has been shown by gamma camera imaging of patients following infusion of 131I-labelled antibody to localize in primary osteogenic sarcomas.
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PMID:Interferon-alpha conjugation to human osteogenic sarcoma monoclonal antibody 791T/36. 657 42

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-beta (TGF-beta) superfamily and are crucial factors in the process of bone formation. Despite knowledge on their wide distribution and expression, however, there is very little information on the biological factors that affect gene transcription of these osteoinductive agents. To investigate this aspect of BMP gene regulation we have studied the effect of a number of factors known to affect osteogenic cells. Northern analysis showed modulation of the expression of BMP-2 and BMP-4 mRNAs in two human osteosarcoma cell lines, MG63 and Saos-2, by prostaglandin E2 (PGE2), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interferon-alpha (IFN-alpha), retinoic acid and 1,25(OH)2 vitamin D3. mRNA expressions of the normally used "housekeeping genes", glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and beta-actin, were found to be susceptible to influence by some of the factors used. Hence, an oligo(dT)15-18 probe was used to reliably estimate the relative quantities of mRNA present for normalization of data. In general, all factors down-regulated mRNA expressions of BMP-2 and BMP-4 in MG63 cells. IL-6 completely abolished detectable expression of BMP-2 mRNA, which was also greatly reduced by IL-1beta, retinoic acid and 1,25(OH)2 vitamin D3. PGE2 had similar influences on BMP-2 and BMP-4 expressions, showing reductions to approximately 60% of normal. In Saos-2 cells only 1,25(OH)2 vitamin D3 had any great effect on BMP-2 expression, which was down-regulated to approximately 60% of control values. BMP-4 was down-regulated by IFN-alpha (approximately 60%) and IL-1beta (approximately 20%). We conclude that BMPs are subject to regulation by a variety of factors and that this is dependent on the stage of the cell in the osteogenic lineage. Furthermore, the use of GAPDH and beta-actin genes as "housekeeping genes" in expression-modulation studies must be treated with care.
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PMID:Modulation of bone morphogenetic protein-2 and bone morphogenetic protein-4 gene expression in osteoblastic cell lines. 987 11

The purpose of these studies was to determine whether interferon-alpha (IFN-alpha) could enhance the sensitivity of human osteosarcoma cells to the cytotoxic actions of etoposide (VP-16). Cytostasis was determined using a [3H]thymidine incorporation assay, whereas cytotoxicity was quantified by a colony-formation assay. Low concentrations (0.1-5 U/ml) of IFN-alpha enhanced the cytostatic activity of VP-16 against MG-63, SAOS-2, and TE-85 osteosarcoma cells. The cytostatic activity of 1 microM VP-16 rose from 11% to 64%, 9% to 31%, and 10% to 71%, respectively, in the three cell lines when IFN-alpha was present. Survival fraction was also decreased when the osteosarcoma cells were treated with VP-16 + IFN-alpha as compared to either agent alone. The interaction between these two agents was determined to be synergistic rather than additive by interaction index analysis. Similar effects on cytostasis and cytotoxicity were observed when IFN-alpha was combined with Adriamycin but not cisplatin, actinomycin D, vinblastine, or amsacrine. VP-16 uptake was enhanced 12-fold in the presence of IFN-alpha, but this did not appear to translate into an increase in topoisomerase-II (topo-II)-DNA complex formation as quantified by the sodium dodecyl sulfate-KCl precipitation assay. We also could not detect alterations in topo-II expression, topo-II protein production, or cell cycle kinetics that have been shown to correlate with increased VP-16 cell sensitivity. Therefore, at this time the mechanism of enhanced cell sensitivity to the combination treatment remains unclear.
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PMID:Interferon-alpha enhances the sensitivity of human osteosarcoma cells to etoposide. 1043 62


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