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

Bradykinin was found to induce production of IL-6 in human diploid fibroblasts, as well as in a hepatoma-derived cell line, but not in a human melanoma or an osteosarcoma cell line. With the exception of the melanoma cell line, these cells were also found to be responsive to IL-1 beta. The response to bradykinin was faster but less high than that induced by IL-1. Experiments in which IL-1 (-alpha or -beta) and bradykinin were applied simultaneously revealed a synergistic interaction. Of the other cytokines tested, TNF-alpha and IFN-gamma weakly induced IL-6. Neither IL-2, IFN-alpha, nor IFN-beta was able to induce IL-6, either in the absence or the presence of bradykinin. These observations constitute further evidence for the existence of interactions between cytokine and noncytokine peptides, thus linking the neuroendocrine and immune systems.
 ...
PMID:Bradykinin induces interleukin-6 and synergizes with interleukin-1. 193 73

We investigated the in vitro effects of human recombinant interferon alpha (rIFN alpha) and interferon gamma (rIFN gamma) on the proliferation and MCH class II antigen expression of two human osteosarcoma cell lines SAOS-2 and U2-OS. Addition of low concentrations of either rIFN alpha (10 U/mL) or rIFN gamma (100 U/mL) to the cultures almost completely inhibited the 3H-thymidine incorporation in SAOS-2 cells while even high amounts (10,000 U/mL) of rIFN alpha or rIFN gamma did not affect the growth rate of U2-OS cells. This difference was not caused by lack of IFN receptors in U2-OS cells since both cell lines responded to rIFN gamma treatment with rapid accumulation of HLA class II mRNA and de novo surface expression of HLA-DR, -DP and -DQ antigens. The induced HLA class II antigens were functionally intact. Osteosarcoma cells treated with rIFN gamma stimulated a mixed lymphocyte culture (MLC) response in allogeneic T-lymphocytes while untreated osteosarcoma cells were unable to provoke T-lymphocyte proliferation. These findings indicate that IFNs display divergent effects on two phenotypically closely related tumor cell lines. This should be appreciated also when therapeutic effects of IFNs are evaluated.
 ...
PMID:Divergent in vitro effects of recombinant interferons on human osteosarcoma cells. 212 12

Highly purified interleukin 1 (IL 1) obtained from stimulated human monocytes appeared to be growth inhibitory and cytocidal for a human melanoma cell line, A375. Although IL 1 did not have an immediate cytolytic effect, with time in culture the growth of the target cells was irreversibly inhibited. The cells eventually lysed and decreased markedly in number; the IL 1 effect can therefore be said to be cytocidal. IL 1 activity could not be separated from the cytocidal activity by a variety of chromatography procedures by using conventional and high-performance liquid chromatography (HPLC). The A375 melanoma cell line was also sensitive to another human cytokine alpha-lymphotoxin (alpha-LT) derived from a human B cell line. IL 1 also appeared to be partially growth inhibitory and cytocidal for a LT-sensitive mouse fibroblast cell line, L929; but not for LT-resistant cells, including a subline of L929; a human epithelial carcinoma cell line, HeLa; a human osteosarcoma cell line, HOS; and a mouse SV40-transformed kidney cell line, TU5. However, the LT-sensitive mouse fibroblast cell line, L-M, was resistant to IL 1. Therefore, the cytocidal activity of IL 1 only partially overlapped the target cell selectivity of alpha-LT. Although natural IFN-alpha and recombinant IFN-beta were appreciably growth inhibitory for the A375 cell line, natural and recombinant IFN-alpha and recombinant IFN-beta and IFN-gamma exhibited little cytocidal activity. Purified IL 1 did not have any antiviral activity, and conversely, IFN and alpha-LT were not co-mitogenic for thymocytes. Furthermore, by ELISA and radioimmunoassays, antibodies against human alpha-LT, tumor necrosis factor, and IFN-gamma did not react with IL 1, indicating that IL 1 is antigenically distinct from these other cytokines. These in vitro results suggest that IL 1 may play a role in host defense against some tumors as a cytocidal factor.
 ...
PMID:Human interleukin 1 is a cytocidal factor for several tumor cell lines. 241 93

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.
 ...
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.
 ...
PMID:Interferon effects on osteoinduction. 248 37

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.
 ...
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.
 ...
PMID:Effect of human interferon-alpha and interferon-gamma on growth, histology, and DNA content of human osteosarcomas in nude mice. 250 87

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.
 ...
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.
 ...
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.
 ...
PMID:Comparison of growth inhibiting effect of natural and recombinant interferon-alpha on human osteosarcomas in nude mice. 347 20


1 2 3 4 5 Next >>