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)

Levels of 9 different oncoproteins and growth factors were assayed by immunoblotting with monoclonal antibodies in 91 serum samples collected between March 1983 and August 1987 from 46 pneumoconiosis patients (36 asbestosis, 10 silicosis) at high risk for the development of cancer. Follow-up of these patients through June 1991 showed that 18 had developed cancer (11 lung, 2 pleural mesothelioma, 2 transitional-cell carcinomas of the urinary bladder, 1 osteosarcoma, 1 non-Hodgkin's lymphoma, 1 adenocarcinoma of the gallbladder). Increased serum levels of ras oncogene-related protein (p21) were found in 7 of the 18 patients who developed cancer (5 lung, 2 pleural mesothelioma) versus 2 of the 28 patients without cancer, a statistically significant difference (p = 0.012). In addition, 6 of the 7 p21-positive cancer cases had positive serum samples prior to clinical diagnosis of disease (average = 16.3 months, range = 3-26 months prior to diagnosis), suggesting that elevated serum p21 levels may be a useful marker for earlier detection in a significant percentage of respiratory malignancies. Finally, elevated serum levels of PDGF-related protein were detected significantly more frequently in advanced pneumoconiosis cases (ILO radiographic classification of 2/1 or greater) than in less advanced cases (80% vs. 41.9%; p = 0.016), and there was a tendency for these PDGF-positive patients to have progression of their disease (68.2% vs. 41.7%; p = 0.065), suggesting that elevated serum PDGF levels may be a marker for the development of severe and progressive pneumoconioses.
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PMID:Serum oncoproteins and growth factors in asbestosis and silicosis patients. 131 98

Platelet-derived growth factor (PDGF) is a potent mitogen for cells of mesenchymal origin. We previously demonstrated that PDGF is produced by osteogenic sarcoma cells. We report here that normal human bone-derived cells produce PDGF and that these cells have an osteoblastic phenotype. This was demonstrated by use of a double immunofluorescent technique and by examining cloned human adult osteoblasts. Northern blot analysis indicates that PDGF production is accounted for by expression of the PDGF-A gene. PDGF-AA and PDGF-BB generally stimulated thymidine incorporation in normal human bone explants to a similar extent. All of the cloned human osteoblasts responded to PDGF-BB while the response to PDGF-AA varied. Similarly, five cloned osteoblastic cell populations were shown to produce PDGF while one did not. This result supports the hypothesis that there are different osteoblastic cell populations that differ in their growth factor responses or in the production of growth factors. Our results suggest that PDGF-BB has the potential to act as a paracrine factor for normal human osteoblasts because all of the osteoblastic cell populations responded to PDGF-BB. None of the osteoblastic cell populations expressed the PDGF-B gene, indicating that it would not act as an autocrine factor. Although not definitive, our results suggest that PDGF-AA has the potential to act as an autocrine factor because osteoblastic bone cell populations were shown to express the PDGF-A gene and respond to PDGF-AA.
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PMID:Human osteoblasts synthesize and respond to platelet-derived growth factor. 183 27

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

To clarify the relationship between oncogene c-sis expression and tumorigenesis in human osteosarcoma, in situ hybridization and immunohistochemical studies were performed to detect c-sis mRNA and PDGF-like protein partially consisting of c-sis product. Formalin fixed-paraffin embedded sections of eight cases of osteosarcoma of bone were examined. Three osteosarcomas highly expressed c-sis mRNA with a fine granular pattern in their cytoplasms. Five osteosarcomas, including three cases with c-sis expression, contained PDGF-like protein in their cytoplasms. These results suggested that c-sis oncogene and PDGF-like protein were closely related to tumorigenesis in human osteosarcoma. The DNA-mRNA in situ hybridization technique applied by the author is as efficient as the immunohistochemical method in cancer research.
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PMID:[Detection of c-sis transcripts and PDGF-like products by in situ hybridization and immunohistochemical study]. 258 31

Platelet-derived growth factor, PDGF, is a potent mitogen for cells of mesenchymal origin such as fibroblasts, smooth muscle cells and glial cells. PDGF is thought to have the potential to act as both a paracrine and an autocrine factor. Studies described here extend these observations to human bone-derived cells. Exogenous PDGF induces biologic activity in two human osteogenic sarcoma cell lines and in one of these, the two PDGF genes, PDGF-1 and PDGF-2/c-sis are expressed. In addition, PDGF stimulates proliferation of normal osteoblastic cells derived from adult human cancellous bone. The expression of the PDGF-1 gene but not the PDGF-2/c-sis gene is demonstrated in normal human adult bone-derived cells by Northern blot analysis and synthesis of PDGF is shown by immunoprecipitation with PDGF antisera. These studies indicate that PDGF has the potential to act as a paracrine or autocrine regulator of bone cells.
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PMID:The potential role of platelet-derived growth factor as an autocrine or paracrine factor for human bone cells. 263 Jan 71

Previous studies have shown that suramin reveals specific PDGF binding sites on U-2 OS human osteosarcoma cells. Studies presented here indicate that U-2 OS cells pretreated with suramin internalize and degrade 125I-PDGF and respond to PDGF by increased tyrosine kinase activity and amino acid transport. However, DNA synthesis in these cells is not reduced by incubation with the PDGF blocking agent suramin and is not stimulated by exogenous PDGF. These data indicate that U-2 OS cells possess functional PDGF receptors but that high levels of DNA synthesis in these cells is unrelated to the binding of secreted PDGF to these cell surface receptors. Thus, it is unlikely that the PDGF mitogen produced by U-2 OS cells stimulates proliferation through an autocrine mechanism involving secretion and subsequent binding to PDGF receptors.
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PMID:DNA synthesis in U-2 OS human osteosarcoma cells is independent of PDGF binding to functional cell surface receptors. 284 Apr 34

The platelet-derived growth factor receptor (PDGF-R), a 180-kDa single-chain polypeptide, was purified from membranes of the human osteogenic sarcoma cell line MG-63. Purification was achieved by treatment of membranes with PDGF and ATP, followed by solubilization with nonionic detergent and successive chromatography on solid-phase anti-phosphotyrosine monoclonal antibody and DEAE-cellulose. The PDGF-R, which was estimated to be 50-80% pure by NaDodSO4/polyacrylamide gel electrophoresis of 32P-labeled preparations, was free of contaminating epidermal growth factor receptor and had no detectable phosphatase activity. It specifically bound 125I-labeled PDGF, a reaction quantified by binding of the ligand-PDGF-R complex to the anti-phosphotyrosine antibody. The purified receptor displayed PDGF-stimulatable tyrosine kinase activity, assayed by autophosphorylation of PDGF-R at tyrosine residues and by phosphorylation of angiotensin II. The Km for ATP in the autophosphorylation reaction was 7.5 microM. Addition of PDGF did not change the Km but increased the Vmax 1.7-fold.
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PMID:Purified human platelet-derived growth factor receptor has ligand-stimulated tyrosine kinase activity. 301 45

PDGF isolated from platelets and forms of PDGF produced by cells transformed with the v-sis gene (PDGF B chain) or U-20S osteosarcoma cells which express the PDGF A chain gene are known to be processed as disulfide-linked dimers of approximately 30 kd. Western blot analysis with anti human PDGF antibody of the PDGF-like factor synthesized and secreted by human blood monocytes (MDGF) on SDS gels indicates that it lacks interchain disulfide bridges and behaves as a 16-kd monomer under nonreducing conditions. Additionally, MDGF exhibits different sensitivities to either formic acid or CNBr cleavage compared to PDGF A or B chain molecules indicating it may have a different primary structure. These data suggest that MDGF represents a unique form of PDGF which lacks interchain disulfide bridges and may represent a new member of the PDGF family of growth factors.
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PMID:Human peripheral blood monocytes secrete a unique form of PDGF. 306 88

Platelet-derived growth factor (PDGF), as purified from fresh human platelets, is a protein of relative molecular mass (Mr) 30,000 composed of two disulphide-linked subunit chains of similar size, named A and B (ref. 1). The dimer structure of PDGRF seems to be important for its biological effects, as reduction irreversibly inactivates the factor; it is not known, however, whether PDGF exists as a heterodimer or as a mixture of homodimers. Amino-acid sequence analysis has revealed that the A- and B-chains of human PDGF are related to each other, and that the B-chain is almost identical to part of the v-sis gene product of simian sarcoma virus (SSV). There is experimental evidence that a PDGF-like protein is indeed operational in SSV-induced transformation and the biologically active v-sis product is probably structurally similar to a putative dimer of PDGF B-chains. PDGF-like growth factors and/or a 4.2-kilobase (kb) c-sis transcript are present in several transformed mammalian cell lines and in certain nontransformed cells; cloned c-sis complementary DNA from human T cells transformed with human T-lymphotropic virus (HTLV) or from human endothelial cells contains the coding sequence for a putative PDGF B-chain precursor, but apparently lacks PDGF A-chain sequences. We have previously partially purified and characterized a PDGF-like growth factor from U-2 OS cells (osteosarcoma-derived growth factor, ODGF) and shown that this factor has structural, functional and immunological characteristics in common with PDGF. We describe here a procedure for the preparation of homogeneous ODGF, and provide evidence that this factor, which binds to the PDGF receptor, has a structure similar to a homodimer of PDGF A-chains.
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PMID:A human osteosarcoma cell line secretes a growth factor structurally related to a homodimer of PDGF A-chains. 345 80

A cDNA clone of about 2300 base pairs was prepared from the human osteosarcoma cell line U-2 OS by hybridization with a 22-mer oligonucleotide complementary to the NH2-terminus of PDGF-A. Restriction and sequence analysis showed that this clone contains the entire coding region for PDGF-A and a long 3'-untranslated region which is only distantly related to that in the mRNA of PDGF-B.
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PMID:The long 3'-untranslated regions of the PDGF-A and -B mRNAs are only distantly related. 366 50


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