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)

The subcellular localization of the retinoblastoma (RB) protein has been studied in primate cell lines by immunofluorescence staining using different monoclonal and polyclonal antibodies. The protein appeared as granules of heterogeneous size over the interphase nuclei. Computer assisted digital overlap analysis indicated that it was predominantly localized in euchromatic areas with low DNA density. The largest RB positive grains lined up on the heterochromatin/euchromatin boundary. During mitosis, the RB protein dissociated from the condensing chromosomes. It was dispersed throughout the cytoplasm during metaphase and anaphase, and it reassociated with the decondensing chromatin during telophase. A new monoclonal antibody, designated aRB1C1, was raised against a bacterial TrpE/human retinoblastoma protein. It specifically recognized the nonphosphorylated and differentially phosphorylated forms of the RB protein in immunoprecipitation experiments. A collection of RB expressing cell lines gave a positive staining reaction with the antibody, whereas the RB negative Weri-RB-27 retinoblastoma and OHS osteosarcoma cells failed to react. Wild-type RB complementary DNA was introduced into Weri-RB-27 by retrovirus mediated gene transfer. Similar experiments were performed with the DU145 prostatic carcinoma cell line that expresses a mutant RB protein. Reconstituted cells of both lines expressed the normal size RB protein and gave a positive immunofluorescence reaction with the aRB1C1 and other anti-RB antibodies. The new monoclonal antibody, however, showed cell type dependent differences of the staining pattern compared to other anti-RB antibodies, suggesting differentiation dependent accessibility to its epitope.
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PMID:Subcellular localization of the retinoblastoma protein. 206 97

The product of the retinoblastoma (Rb) gene can form complexes with the transforming proteins of small DNA tumor viruses, including SV40 large T antigen (Tag), adenovirus E1A, and the human papilloma virus E7. The strong correlation between their ability to transform and their ability to bind Rb protein suggests that these oncoproteins exert their effect through blocking the Rb function. SV40 Tag causes oncogenic cell transformation of rodent cells, and it is also required for viral DNA replication. In this paper, we investigated the effect of the Rb protein on the SV40 replication associated function of Tag. We present evidence suggesting that the complex formation between Rb and Tag interferes with the viral DNA replication. In Y79 retinoblastoma and Saos-2 osteosarcoma cells, which lack functional Rb protein, a SV40 based plasmid vector, pSVEpR4, replicates well. In the same cells reconstituted for Rb expression with an intact Rb gene introduced by retroviral mediated gene transfer, pSVEpR4 replicates to a considerably lower level. The inhibitory effect of Rb protein was surmounted by increasing the intracellular level of Tag. Increasing amounts of Tag in wild-type Rb negative Y79 cells had virtually no effect on SV40 replication. Furthermore, the overexpression of Tag in Rb reconstituted Y79 cells did not alter the growth rate of the cells. These data suggest that Rb protein interacts with Tag and modulates its ability to promote SV40 DNA replication.
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PMID:Reintroduction of a normal retinoblastoma gene into retinoblastoma and osteosarcoma cells inhibits the replication associated function of SV40 large T antigen. 206 98

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) promotes the growth of a variety of hematopoietic and nonhematopoietic cells, both benign and malignant. There is now evidence that osteoblast-like cells produce GM-CSF and their growth is stimulated by this cytokine in vitro. We have studied the effect of rhGM-CSF on DNA synthesis and cell proliferation in the human osteogenic sarcoma cell lines U-20S, G-292, MG-63, and HOS. RhGM-CSF stimulated a dose-dependent increase in radioactive thymidine incorporation in each of the four cell lines in the presence of serum-free media, and in two cell lines (HOS and U-20S) in the presence of fetal bovine serum (FBS). In addition, rhGM-CSF produced significant increases in cell proliferation in two cell lines (MG-63 and U-20S) in the presence of 2% FBS. These results suggest that GM-CSF may have an important role in the biology of human osteogenic sarcoma cells. The clinical implications of these findings merit further investigation.
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PMID:The effect of rhGM-CSF on the proliferation of osteogenic sarcoma cells. 206 68

Biological interactions between human cytomegalovirus (HCMV) and the human immunodeficiency virus type 1 (HIV-1) were analysed in transfection and infection experiments, carried out in a human osteogenic sarcoma cell line (HOS) and in the same cell line chronically infected with HCMV (E155). When HOS and E155 cells were transfected with recombinant plasmids containing the HIV long terminal repeat (LTR) linked to the bacterial chloramphenicol acetyltransferase (CAT) gene, LTR-directed CAT expression was 20 times higher in E155 cells than in HOS cells. HOS cells co-infected with HCMV and HIV-1 showed enhanced production of the HIV-1 p24 antigen. In reciprocal experiments, an increase in HCMV immediate early gene expression was observed when HCMV-infected HOS cells and E155 cells were either transfected with a recombinant plasmid containing the HIV transactivator gene (pTAT), or when infected with HIV-1. DNA hybridization analysis of E155 and HCMV-infected HOS cells revealed higher levels of HCMV DNA in cells transfected with pTAT than in cells transfected with other non-specific recombinant plasmids. E155 cells transfected with pTAT also produced higher titres of infectious HCMV than control cultures of E155 cells transfected with other recombinant plasmids, including pMTAT carrying a mutant tat gene. The functional reciprocity in vitro between HCMV and HIV is discussed with respect to its possible implications for the clinical development of AIDS.
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PMID:Reciprocal enhancement of gene expression and viral replication between human cytomegalovirus and human immunodeficiency virus type 1. 215 40

Simian virus 40 T antigen is a multifunctional protein which has recently been shown to form a complex with the retinoblastoma susceptibility gene product (Rb protein) (J.A. DeCaprio, J.W. Ludlow, J. Figge, J.-Y. Shaw, C.-M. Huang, W.-H. Lee, E. Marsilio, E. Paucha, and D.M. Livingston, Cell 54:275-283, 1988; P. Whyte, K.J. Buchkovich, J.M. Horowitz, S.H. Friend, M. Raybuck, R.A. Weinberg, and E. Harlow, Nature (London) 334:124-129, 1988). This interaction may facilitate some of the functions of T antigen. The ability of simian virus 40 T antigen to mediate transcriptional activation and viral DNA replication was tested in human osteosarcoma cell lines U-2OS and Saos-2, which are Rb positive and Rb negative, respectively. Both functions of T antigen were efficient in both cell lines. Hence, these functions can occur in the absence of Rb protein.
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PMID:Simian virus 40 T antigen can transcriptionally activate and mediate viral DNA replication in cells which lack the retinoblastoma susceptibility gene product. 215 11

In order to segregate multiple activities ascribed to IL-1, various human IL-1 alpha derivatives were produced by recombinant DNA technology. A derivative substituted at the 151st Asp with Tyr(termed to be TN-55) showed unique characteristics. TN-55 lost the PGE2 inducing activity in a human osteosarcoma cell line (MG-63) and growth promoting activity for a human dermal fibroblast cell line (CCD-27Sk), but partially remained LAF activity in mouse thymocyte, cytostatic activity against a human melanoma cell line (A-375) and IL-2 inducing activity in a human T cell line (HSB.2). Although TN-55 bound to the receptor on MG-63 cells with a similar affinity as native IL-1 alpha, TN-55 not only failed in inducing PGE2 production but also antagonized the PGE2 inducing action of IL-1 alpha or IL-1 beta. Thus, TN-55 seems to work as a receptor antagonist. Moreover, TN-55 did not stimulate ACTH secretion in rats in vivo. On the other hand, TN-55 induced PGE2 production in a rabbit dermal fibroblast cell line (RAB-9) and exhibited pyrogenicity in rabbits in vivo. These data suggest that TN-55 has different species-cross reactivity from native IL-1 alpha. In conclusion, multiple biological activities of IL-1 alpha can be segregated by substituting one amino acid. TN-55 may be an ideal IL-1 agonist which lacks inflammatory characteristics of IL-1 (e.g. PGE2-dependent activities) in human but partially retained T lymphocyte stimulating activity and tumor cytostatic activity. In addition, TN-55 may also work as an IL-1 antagonist to block PGE2 production induced by IL-1 through receptor competition.
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PMID:A human IL-1 alpha derivative which lacks prostaglandin E2 inducing activity and inhibits the activity of IL-1 through receptor competition. 216 12

Episomal BK virus (BKV) DNA was detected in primary human brain tumours, in Kaposi's sarcoma and in cell lines from brain tumours. Ewing sarcoma and osteogenic sarcoma. Infectious BKV was rescued from several tumours and tumour cell lines by transfection of total cellular DNA into human embryonic fibroblasts. Restriction endonuclease and nucleotide sequence analysis showed that all the rescued viruses are similar to BKV-IR, a BK variant previously isolated from a human tumour of pancreatic islets, indicating that a specific BKV strain may be associated with certain types of human tumours. All the variants contain a putative transposable elements in the regulatory region of the viral genome. This region has mutagenic properties and enhancing activity in transformation, suggesting a possible role of these variants in tumour induction or progression.
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PMID:Characterization of BK virus variants rescued from human tumours and tumour cell lines. 217 63

We have reported previously that parathyroid hormone (PTH) acts on cultured bone cells to stimulate creatine kinase (CK) activity and [3H]thymidine incorporation into DNA via phosphoinositide turnover, in addition to its other actions via increased cyclic AMP production. We also found that mid-region fragments of PTH stimulate [3H]thymidine incorporation into avian chondrocytes. In the present study of mammalian systems, we demonstrate differential effects of defined synthetic PTH fragments on CK activity and DNA synthesis, as compared with cyclic AMP production, in osteoblast-enriched embryonic rat calvaria cell cultures, in an osteoblast-like clone of rat osteosarcoma cells (ROS 17/2.8) and in chondroblasts from rat epiphysial cartilage cell cultures. Unlike full-length bovine (b)PTH-(1-84) or the fully effective shorter fragment human (h)PTH-(1-34), fragments lacking the N-terminal region of the hormone did not increase cyclic AMP formation, whereas they did stimulate increases in both DNA synthesis and CK activity. Moreover, the PTH fragment hPTH-(28-48) at 10 microM inhibited the increase in cyclic AMP caused by 10 nM-bPTH-(1-84). The increase of CK activity in ROS 17/2.8 cells caused by bPTH-(1-84) or hPTH-(28-48) was completely inhibited by either cycloheximide or actinomycin D, as was shown previously for rat calvaria cell cultures. These results indicated the presence of a functional domain of PTH in the central part of the molecule which exerts its mitogenic-related effects on osteoblast- and chondroblast-like cells in a cyclic AMP-independent manner. Since cyclic AMP formation by PTH leads to bone resorption, specific mid-region fragments of PTH might prove suitable for use in vivo to induce bone formation without concomitant resorption.
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PMID:Stimulation by defined parathyroid hormone fragments of cell proliferation in skeletal-derived cell cultures. 217 78

Canine and human osteosarcoma are very similar clinically, radiologically and pathologically. DNA extracted from canine osteosarcomas (n = 9) and normal canine control tissues (n = 17) was examined for amplification of the c-sis, c-myc, N-myc and c-H-ras protooncogenes. Statistically significant amplification of the c-sis and c-myc protooncogenes was evident in the tumor tissues as compared to the normal control tissues (P less than 0.05). DNA and total cellular RNA from cultured canine and human osteosarcoma and fibroblast cell lines were examined for amplification or enhanced expression of c-sis and c-myc. Very low levels of c-myc and c-sis DNA amplification were noted in canine osteosarcoma cells as compared to canine fibroblasts. Immunostaining of sections of human and canine osteosarcoma for the sis gene product, PDGF B, showed similar levels and patterns of expression in both populations of tumors.
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PMID:Low level amplification of c-sis and c-myc in a spontaneous osteosarcoma model. 220 81

We report the case of an otherwise healthy 37-year-old man who had had bilateral enucleation during early childhood for bilateral retinoblastomas, in addition to two cutaneous melanomas (the first appearing at age 27 years). He also had dysplastic melanocytic nevi and a history of cutaneous melanoma in his mother. Retinoblastoma may aggregate in families and is associated with DNA abnormalities of chromosome 13. Recent reports have emphasized the appearance of second malignancies in retinoblastoma survivors. The second malignancies include osteosarcoma, soft tissue sarcoma, and cutaneous melanoma. Cutaneous melanoma also may aggregate in families, usually in the setting of dysplastic melanocytic nevi. The features of this case and of similar reported cases suggest that there may be a greater than expected association between retinoblastoma and cutaneous melanoma.
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PMID:Cutaneous melanoma and bilateral retinoblastoma. 222 30


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