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)

Sections were taken from the center, midzone, and margin of four human osteogenic sarcomas and one fibrosarcoma. Single-cell suspensions of tumors were examined in an indirect immunofluorescence assay with autologous or homologous anti-osteogenic sarcoma antisera as the intermediate reactant and fluorescein-labeled anti-human IgG as the final reactant. Cells were stained under conditions in which the fluorescence intensity was directly proportional to the density of the tumor-associated antigen on these cells. The density of tumor-associated antigen on cells from the center of the five tumor masses was low; cells from the midzone had intermediate levels of tumor antigen density, and cells at the margin had the highest levels. Similar preparations stained with polyspecific anti-HLA antisera did not demonstrate such a gradient. Since osteogenic sarcomas grow outward from the center, with the outer margin populated by the youngest cells, these results suggest that the oldest cells in the tumor bear the least tumor antigen, and the youngest tumor cells have the most. This is not compatible with theories which postulate that the immune system modulates the growth of a tumor so that only the least antigenic cells are allowed to grow. Alternative mechanisms are discussed.
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PMID:Antigenic differences among osteogenic sarcoma tumor cells taken from different locations in human tumors. 6 91

The surface antigenic characteristics of human glial brain tumor (HGBT) cells were studied by complement-dependent cytotoxic antibody assays and indirect membrane immunofluorescence. Eight permanent, well-characterized cell lines derived from human gliomas were used for analysis with antisera raised by hyperimmunization of nonhuman primates (Macaca fascicularis) with glioblastoma multiforme tissue or established HGBT cells lines. Exhaustive absorption of these antisera to remove predominantly antispecies activity rendered HLA nonreactive "preabsorbed" antisera, which reacted with a large panel of gliomatous and nongliomatous human tumor cells; 1 carcinoma, 2 sarcomas, 2 melanomas, 1 neuroblastoma, and 8 HGBT cell lines. Four lymphoblastoid lines and 2 carcinomas were unreactive. After further absorption with a human osteogenic sarcoma cell line, the antisera demonstrated significant levels of reactivity for 8 tested HGBT cell lines and no longer reacted with the nongliomatous cultured tumor cells lines. Therefore, extensive absorption of nonhuman primate anti-human glioma sera removed all activity for the nongliomatous cell lines tested, but it left significant reactivity against a glial tumor cell line-associated antigen(s) present on all 8 human glioma cell lines tested.
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PMID:Surface antigenic characteristics of human glial brain tumor cells. 7 98

In this study we have evaluated the ability of interferons (IFNs) alpha, beta, gamma and Tumor Necrosis Factor (TNF) alpha to modulate the expression of the Major Histocompatibility Complex (MHC) antigens in human osteosarcoma cells. The osteosarcoma cell lines Saos-2 and U-2 OS, treated in vitro with IFNs and TNF alpha, showed an increased expression of class I HLA antigens. However, only IFN gamma and, to a lower extent, IFN beta induced the expression of class II HLA antigens. These effects were dose and time-dependent. Simultaneous treatment with IFN gamma and IFN beta or TNF alpha, which by itself was unable to induce the expression of class II HLA antigens, produced different effects on the two osteosarcoma cell lines: in Saos-2 IFN beta and TNF alpha amplified the effects obtained with IFN gamma alone; in U-2 OS, TNF alpha increased the expression induced by IFN gamma on class II HLA antigens, whereas IFN beta antagonized the effects of IFN gamma. IFN alpha did not influence the induction of class II HLA antigens by IFN gamma in the two osteosarcoma cell lines. IFNs have been introduced in some clinical protocols for the treatment of osteosarcoma, based on their antiproliferative activity. Our findings may contribute to a better knowledge of the effects of IFNs and TNF alpha in osteosarcoma by showing the existence of more complex interactions.
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PMID:Induction of HLA class II antigens in osteosarcoma cells by interferons and tumor necrosis factor alpha. 162 36

A new cell line (SARG) was established from a human radiation-induced osteosarcoma (OSA). It showed an epithelial-like morphology with polymorphous and sometimes bizarre nuclei. SARG had an osteoblastic differentiation pattern: almost 100% of the cells were positive for alkaline phosphatase, type I and III collagens and osteonectin. The expression of class I HLA antigens was detectable even after 40 in vitro passages. The expression of MHC antigens was greatly increased after in vitro treatment with interferon gamma (IFN-gamma), whereas interferon alpha (IFN-alpha) and tumor necrosis factor alpha (TNF-alpha) increased the expression of class I antigens, but not of class II antigens. SARG was tumorigenic after subcutaneous injection in nude mice. Experimental metastases were never detected.
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PMID:SARG: a new human osteosarcoma cell line. Expression of bone markers and of major histocompatibility antigens. 162 59

Cells from various human nonlymphoreticular neoplasms show reduced HLA class I antigen expression. In this report, a system of human fibroblasts transformed by an avian retrovirus has been employed to investigate the mechanism of this phenomenon. Rous sarcoma virus has been used to transform in vitro human dermal fibroblasts, and clonal cell lines have been established from these cultures. In all the clones studied the integration of the provirus induced a reduction of cell-surface HLA-A, -B, -C framework antigen and beta 2-microglobulin expression when compared to levels for the respective parental fibroblasts. The reduction was correlated with a diminished intracellular synthesis of these molecules. Uninfected cells derived from an osteogenic sarcoma exhibited a reduced expression comparable to that of dermal diploid fibroblasts obtained from the same donor and transformed by Rous sarcoma virus. RNA gel blot analysis of total cellular RNA and of poly(A)+ cytoplasmic RNA showed a markedly decreased amount of HLA class I transcripts in the transformed cells. Southern blot study of genomic DNAs digested with several restriction endonucleases showed that the banding patterns of the HLA genes were not altered in the cells harboring the Rous sarcoma provirus. Our data are consistent with the hypothesis that the Rous sarcoma provirus that does not seem to be linked to the major histocompatibility complex class I gene superfamily may negatively control HLA gene expression.
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PMID:Inhibition of HLA class I antigen and mRNA expression induced by Rous sarcoma virus in transformed human fibroblasts. 282 69

Human T cell clones cytotoxic for autologous sarcoma cell lines have been developed from patient JM with an osteogenic sarcoma, and from patients EG and RM with malignant fibrohistiocytoma. These clones were derived from the cocultivation of peripheral blood lymphocytes (PBL) with the respective patient's autologous irradiated established tumor cell lines (AIT). After two cycles of stimulation for 5 days in bulk culture, these "educated" lymphocytes were seeded at a density of 1 X 10(6) cells/well in 24-well plates and were cultured in the presence of highly purified natural IL 2 and AIT, the latter serving as a feeder layer. Cell numbers were reduced from the initial seeding density by one log each week until reaching a density of 10(2) cells. These cells were found to be stable in viability and cytotoxic activity, after which limiting dilution was then performed. Within 4 to 6 wk, clones were isolated with unique specificities. These clones were capable of proliferating to a total density of 10(9) cells/ml and maintained their specific cytotoxicity for more than 6 mo. Testing with a panel of target cells of various histotypes, cold-target inhibition assays, and blocking of cytotoxicity with anti-HLA monoclonal antibodies showed that the T cell clones recognize a common sarcoma-associated antigen and that the lysis is HLA restricted. Phenotypically, cytotoxic clones derived from JM were Leu-1+, Leu-2+, and Leu-3-, whereas those derived from EG exhibited either Leu-24 or Leu-3+ markers, the latter phenotype lacking cytotoxicity. RM exhibited mainly Leu-3+ clones with strong cytotoxicity. All were HNK-1- and HLA class II+, with less than 1% of cells of each clone stained by anti-TAC monoclonal antibody. The clones from each patient did not lyse autologous or allogeneic PBL, mitogen-induced T lymphoblasts, normal fibroblasts, cells isolated from benign neoplasms, carcinoma cells, Daudi B lymphoid cells, or K562 cells. With the exception of EG, all clones produced immune interferon in a range from 12 to 50 U/ml. The generation of long-term specific T cell clones can be used to further dissect the cellular immune response to sarcomas. Cytotoxic T cell clones have potential application for tumor immunotherapy.
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PMID:Cellular immune response to human sarcomas: cytotoxic T cell clones reactive with autologous sarcomas. I. Development, phenotype, and specificity. 309 88

An ultrastructural survey of 11 human tumors passaged in N:NIH(S) (nu/nu) mice showed two instances of type C virus production. In one instance type C virus particles were observed in the endothelial murine stromal cell component of an embryonal carcinoma but not in the human tumor cells. In another instance type C virus particles were seen replicating in the chondroblastic human cells of a xenografted osteosarcoma. The type C virus produced in the human cells failed to transform NIH/3T3 cells, the C-127 rat cell line, or mink cells. Nucleic acid hybridization studies in which a human endogenous retroviral probe and a xenotropic murine leukemia virus envelope probe were used suggested that the retrovirus present in the human osteosarcoma cells is related to murine leukemia viruses. Intracisternal A-particles (IAP) were also detected in the human osteosarcoma cells. Their presence in the human cells was demonstrated by simultaneous visualization of IAP and human HLA determinants at the cell surface. The literature on type C virus infection of human cells and tumors grafted in nude mice is reviewed.
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PMID:Murine type C retroviruses and intracisternal A-particles in human tumors serially passaged in nude mice. 631 Feb 1

Serial serological studies were carried out on 19 of 20 patients with malignant gliomas who were actively immunized with one of two human glioma tissue culture cell lines (D-54MG or U-251MG). Most patients mounted a significant serum reaction to histocompatibility antigens (HLA's), as well as an antibody response to fetal bovine serum (FBS) which was added to the glioma-cell inoculum. These two sources of antibody accounted for greater than 90% of the antibody induced by these inoculations. Two patients continued to have significant amounts of binding antibody to the original immunizing cell line following exhaustive absorptions of FBS and these two had all remaining significant antibody removed by further absorption of the serum against the 2-T osteogenic sarcoma tissue culture cell line known to possess antigens cross-reactive with human gliomas. One single patient continued to show significant antibody binding to the original glioma cell line following absorption against FBS, human platelets, and the 2-T cell line, and therefore seems to have produced glioma-distinctive antibodies in response to immunization. The antibody preparation from this patient was also cytotoxic against the original glioma cell line, as well as another recently cultured human glioblastoma cell line. The significance of these serological studies is discussed as it relates to immunological responses patients with gliomas may make to active immunization.
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PMID:Immunobiology of primary intracranial tumors. Part 8: Serological responses to active immunization of patients with anaplastic gliomas. 660 66

A homogeneous group of 53 Caucasian subjects with high-grade osteosarcoma (OS) was typed for HLA-A and B locus antigens. Although no significant differences in the distribution of these antigens were found in comparison with 425 local controls, a trend towards an increase of HLA-B18 and decrease of HLA-B12 was observed. All the patients underwent amputation plus adjuvant chemotherapy and among the 29 patients with a follow-up longer than one year, 9 out of 10 subjects with HLA-A3 antigens developed metastases within a few months. None of the OS patients had the HLA-A3, B7 haplotype which is present in linkage-disequilibrium in the control population.
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PMID:Frequency and prognostic value of HLA antigens in osteosarcoma patients. 698 58

Traditionally, heat shock proteins (HSPs) are believed to be located intracellularly, where they perform a variety of chaperoning functions. Recently, evidence has accumulated that some tumor cells express HSPs on the cell surface. The present study confirms this finding and correlates HSP72 cell surface expression, induced by nonlethal heat shock, with an increased sensitivity to interleukin-2-stimulated CD3-natural killer (NK) cells. After nonlethal heat shock, a monoclonal antibody directed against the major heat-inducible 72-kD HSP (HSP72) stains the cell surface of sarcoma cells (ie, Ewing's sarcoma cells or osteosarcoma cells) but not that of normal cells (ie, peripheral blood lymphocytes, fibroblasts, phytohemagglutin-stimulated blasts, B-lymphoblastoid cell lines) or of mammary carcinoma cell line MX-1 carcinoma cells. In this study, we show for the first time a correlation of HSP72 cell surface expression with an increased susceptibility to lysis by NK effector cells. This finding is supported by the following points: (1) HLA-disparate effector cells show similar, elevated lysis of HSP72+ heat-treated sarcoma cells; (2) CD(3-) NK cells, but not CD3+ cytotoxic T lymphocytes, are responsible for the recognition of heat-shocked sarcoma cells; (3) by antibody-blocking studies, an immunogenic HSP72 determinant, which is expressed selectively on the cell surface of heat-treated sarcoma cells could be correlated with NK recognition; (4) the reported phenomenon is independent of a heat-induced, transient downregulation of major histocompatibility complex (MHC) class-I expression; and (5) blocking of MHC class-I-restricted recognition, using either MHC class-I-specific monoclonal antibody W6/32 on the target cells or alpha/beta T-cell receptor monoclonal antibody WT31 on effector cells, also has no inhibitory effect on the lysis of HSP72+ tumor cells. Finally, our in vitro data might have further clinical implications with respect to HSP72 as a stress-inducible, sarcoma-specific NK recognition structure.
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PMID:CD3- large granular lymphocytes recognize a heat-inducible immunogenic determinant associated with the 72-kD heat shock protein on human sarcoma cells. 763 45


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