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)

The human osteosarcoma cell line (OST-1-PF) can grow in protein-free Coon's modified Ham's F12 medium. Growth of the cells in protein-free medium was partially density-dependent and partially depressed by medium change. An extract and conditioned medium of OST-1-PF cells contained high mitogenic activity for BALB/c3T3 cells. The growth factor in the cells was purified and identified as a basic fibroblast growth factor (bFGF)--like factor on the basis of its elution profile on heparin-affinity chromatography and the result of immunoblotting. An unidentified factor in a conditioned medium eliciting most of the DNA synthesis-stimulating activity showed a weak affinity for heparin. Various additions, including serum and growth factors, stimulated the growth of OST-1-PF cells in protein-free medium. Of these factors, epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), acidic fibroblast growth factor (aFGF) and bFGF were the most potent mitogens. High-affinity receptors of EGF and FGF were found on the surface of these cells. These results indicate that autonomous growth of OST-1-PF cells in protein-free medium is mainly controlled by an intracellular mechanism.
 ...
PMID:Roles of various growth factors in growth of human osteosarcoma cells which can grow in protein-free medium. 158 71

We have previously characterized human smooth muscle myosin light chain (MLC)-2 isoform by complementary DNA cloning and have shown that this isoform is expressed in a number of nonmuscle cells such as fibroblast cells. In this report, we show that when human osteosarcoma derived clonal cells (TE 85 clone F-5) (HOS), which are immortalized and nontumorigenic, undergo transformation following infection by Kirsten murine sarcoma virus (K-HOS) or by a chemical carcinogen [N-methyl-N-nitro-N-nitrosoguanidine (MNNG-HOS)], the smooth muscle MLC-2 mRNA is repressed. Revertants of transformed K-HOS cells (K-HOS312H) show normal levels of smooth muscle MLC-2 mRNA. Transformation of HOS cells by Ha-ras oncogene sequences, either by retroviral infection or by transfection followed by selection for tumorigenic cells in nude mice, results in complete repression of smooth muscle MLC-2 mRNA level. Treatment of HOS cells with tumor promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, results in repression of smooth muscle MLC-2 mRNA. Smooth muscle MLC-2 mRNA level is repressed in many, but not all, transformed cell lines, suggesting that it is not an indirect consequence of transformation but is specific to the agent that brings about transformation. HOS cells synthesize three MLC-2 protein species resolved by the two-dimensional gel electrophoretic system. The identity of the smooth muscle MLC-2 isoform was established by coelectrophoresis of the in vitro synthesized MLC-2 protein corresponding to the cloned complementary DNA in the two-dimensional gel system along with total [35S]methionine labeled HOS cell proteins. Quantitative analysis of MLC-2 isoforms in different HOS cells indicates that the synthesis of smooth muscle MLC-2 isoform is specifically repressed to an undetectable level in ras transformed and MNNG transformed cells and also following treatment with 12-O-tetradecanoylphorbol-13-acetate.
 ...
PMID:Human smooth muscle myosin light chain-2 gene expression is repressed in ras transformed fibroblast cells. 159 78

2,3-Dihydrophthalazine-1,4-dione derivatives demonstrated potent cytotoxicity against the growth of murine leukemia cells and human single cell suspension, i.e. Tmolt3 leukemia and HeLa-S3, as well as colon adenocarcinoma and KB nasopharynx. However, only select compounds demonstrated activity against bronchogenic lung, osteosarcoma and glioma growth. 2,3-Dihydrophthalazine-1,4-dione was active in vivo against L1210 leukemia, Lewis lung and Ehrlich ascites carcinoma growth. In L1210 cells the agents inhibited both DNA and RNA synthesis, and a few of the compounds were capable of inhibiting protein synthesis at 3 times their ED50 values. When 2,3-dihydrophthalazine-1,4-dione and N-butyl-2,3-dihydrophthalazine-1,4-dione were examined for their mode of action in the L1210 lymphoid leukemia cells, the sites of inhibition by the agents appear to be the de novo purine pathway at the enzymes IMP dehydrogenase and PRPP amido transferase. IMP dehydrogenase activity was inhibited at least 45% by 45 min at 100 microM concentration of drugs whereas the remaining enzymes that were affected by the drugs were not inhibited as early. Secondary sites were dihydrofolate reductase and thymidylate synthetase. The d(NTP) levels were also reduced specifically dATP and dCTP levels.
 ...
PMID:The anti-neoplastic activity of 2,3-dihydrophthalazine-1,4-dione and N-butyl-2,3-dihydrophthalazine-1,4-dione in human and murine tumor cells. 162 17

The patient with quadruple cancer was a 32 year-old female who had osteosarcoma, bilateral breast cancer and adenocarcinoma of the lung. When chromosomal analysis of peripheral blood lymphocyte was performed, two abnormal cells were detected among 42 cells examined. The first cell showed a translocation involving chromosome 1 and 20 and trisomic for chromosome 19. The second cell was trisomic for chromosome x. Southern blot analysis of DNA from peripheral blood lymphocyte revealed that there was no difference in the expression of Rb gene between the patient and healthy adult.
 ...
PMID:[Chromosome and DNA analyses of peripheral blood lymphocyte from the quadruple cancer patient]. 162 41

During continuous culture with serial passage, the human osteosarcoma cell line SaOS-2 showed a time-dependent decrease in skeletal alkaline phosphatase (ALP) activity. Because this was indicative of heterogeneity, subpopulations of SaOS-2 cells were isolated from replicate low-density cultures. The subpopulations were less heterogeneous and more stable (with respect to ALP) than the parent population. ALP specific activity in the subpopulations ranged from 0.05 to 2.3 U/mg protein, and cytochemical analyses indicated multiple steady-state levels of ALP activity per cell. The amount of ALP activity in SaOS-2 subpopulations was proportional to collagen production ([3H]proline incorporation into collagenase-digestible protein; r = .84, P less than .005), and to parathyroid hormone (PTH)-linked synthesis of cyclic adenosine monophosphate (cAMP) (r = .88, P less than .01). From these data, we inferred that ALP activity in SaOS-2 cells can provide a useful index of the osteoblastic phenotype, and that ALP activity, collagen production, and PTH-linked adenylate cyclase were coordinately regulated in these osteoblast-like osteosarcoma cells (ie, selection of subpopulations for ALP activity coselected for collagen synthesis and PTH-linked synthesis of cAMP). Further comparative studies showed that micromolar fluoride concentrations stimulated cell proliferation ([3H]thymidine incorporation into DNA) in low-ALP SaOS-2 subpopulations, but not in high-ALP cells (P less than .001), and that this differential sensitivity to fluoride was associated with an inverse correlation between fluoride-sensitive acid phosphatase and ALP activities (r = -.91, P less than .001).
 ...
PMID:Skeletal alkaline phosphatase specific activity is an index of the osteoblastic phenotype in subpopulations of the human osteosarcoma cell line SaOS-2. 165 38

The gene for rat bone gla protein (BGP) was isolated and 1250 basepairs (bp), including 1100 bp of 5' flanking DNA, were placed up-stream of the human GH reporter gene. After transient transfection into the osteoblast-like rat osteosarcoma cell line ROS 17/2.8, the BGP promoter demonstrated a low level of basal activity that was increased approximately 10-fold by the addition of 10(-8) M 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. A single 250-bp fragment (-523 to -274) was sufficient to confer hormone inducibility upon both heterologous and homologous promoters. Deletion studies, complemented by evaluation with synthetic oligomers, enabled localization of the 1,25-(OH)2D3 response element to within 19 bp (-456 to -438), containing an element with an imperfect direct repeat [GGTGA(N4)GGACA] and homology to other steroid-responsive elements. Gel retardation assays demonstrated that partially purified chick intestinal 1,25-(OH)2D3 receptor bound specifically and with high affinity to a DNA fragment containing the putative 1,25-(OH)2D3 response element, and this binding was perturbed by monoclonal antibodies to the 1,25-(OH)2D3 receptor. Surprisingly, the 250-bp fragment, when linked in an antisense orientation with respect to the BGP promoter, blocked basal and hormone-dependent gene expression. However, a 246-bp fragment 5' to the 250-bp element (-1100 to -855) restored 20-fold inducibility when linked to the first fragment in the same orientation, suggesting cooperativity between at least two elements to achieve the hormonal regulation observed in this gene.
 ...
PMID:The vitamin D-responsive element in the rat bone Gla protein gene is an imperfect direct repeat that cooperates with other cis-elements in 1,25-dihydroxyvitamin D3- mediated transcriptional activation. 165 93

Histologic slides of 22 soft tissue tumors (9 malignant fibrous histiocytoma, 8 fibrosarcoma, 2 rhabdomyosarcoma, 2 osteosarcoma, 1 Askin tumor) were Feulgen stained. Using an automated image analyzing system (Cambridge 570) at low magnification (25x), the tumor cell nuclei were segmented. The geometrical center of the nuclei was considered the vertex. A basic graph was constructed according to the neighborhood condition of O'Callaghan. Neighboring tumor cell nuclei were visualized by connecting edges. Several features of tumor cell nuclei were measured, including area, surface, major and minor axis of best fitting ellipsis and extinction (DNA content). Nuclear features are attributed to the vertices. The differences, or "distances," between features of connected vertices are attributed to the corresponding edges, which are dependent on the attributes. Thus, different minimum spanning trees (MST) result. Each MST can be decomposed into clusters using a suitable decomposition function on the edges, which rejects an edge if its attributes differ from the mean of the attributed values of surrounding edges more than a neighbor dependent bound (lower limit). Taking into account the length and other attributes of edges (e.g., differences in orientation of the major axis), clusters of different nuclear orientation can be detected. A cluster tree can be constructed by defining the geometric center of a cluster as a new vertex, and by computing the neighborhood of the cluster vertices. The result is an attributed MST containing characteristic structural properties of the image (in cases of sarcomatous tumors, local orientation of tumor cell nuclei and local DNA abnormalities).
 ...
PMID:Analysis of soft tissue tumors by an attributed minimum spanning tree. 166 87

Inactivation of the retinoblastoma gene appears to have a fundamental role in the genesis of retinoblastoma, osteosarcoma, and other malignant tumors. The gene is generally inactivated because of loss-of-function mutations, although epigenetic phenomena, such as hypermethylation of the promoter region, could possibly have the same effect. We investigated the methylation pattern at the 5' end of the retinoblastoma gene, including its promoter region and exon 1, in DNA purified from 56 primary retinoblastomas. We found five tumors with evidence for hypermethylation, all from unilateral, simplex patients. No methylation abnormalities were detected in DNA purified from the leukocytes from these patients. It is interesting that in one of these tumors the hypermethylation was confined to one allele. There were no mutations in a 1,306-bp sequence including the hypermethylated region that might account for the allele-specific hypermethylation. We believe that the hypermethylation of the retinoblastoma gene that we found in these tumors corresponds to the allelic inactivation of the gene, and we speculate that erroneous hypermethylation without alteration of nucleotide sequence occasionally plays a role in the genesis of this cancer. If this is true, then retinoblastomas with hypermethylation might be treatable with chemotherapeutic agents that interfere with methylation of DNA.
 ...
PMID:Allele-specific hypermethylation of the retinoblastoma tumor-suppressor gene. 167 87

Various sublines of cells established from an osteosarcoma that developed in a patient (O.H.) with previous bilateral retinoblastoma were examined for different restriction fragment-length polymorphisms of chromosome 13q, as well as for rearrangements of the retinoblastoma gene using a cDNA probe. The independently established sublines were used to help separate primary and secondary events taking place in tumorigenesis of the osteosarcoma of this patient. Information from the present DNA analysis, taken together with data from cytogenetic and enzymatic studies on chromosome 13 in the cell lines, revealed both common and distinct genetic changes on chromosome 13q. The common changes may indicate the nature of the first and second mutational events in the development of the osteosarcoma. The first, constitutional cancer predisposing mutation seemed to be a base mutation or a small deletion/insertion, and the second event involved a deletion of a larger part of the long arm of chromosome 13. The distinct genetic changes included other deletion and duplication events of chromosome 13q. The existence of multiple sublines with different genetic constitutions provides improved possibilities for gaining insight into the nature of the genetic lesions leading to tumor formation, as these may reflect the clonal variation present in the primary tumor. We also demonstrate the difficulty of inferring from single tumor cell isolates to properties of the primary tumor.
 ...
PMID:Chromosome 13 alterations in osteosarcoma cell lines derived from a patient with previous retinoblastoma. 168 33

Mutational inactivation of the retinoblastoma (RB) gene has been implicated in the genesis of retinoblastoma, osteosarcoma, and other human tumors. Our strategy has been to characterize naturally occurring mutants from tumor cells to pinpoint potential domains of RB protein crucial for tumor suppression. We show here that osteosarcoma cell line Saos-2 contains an abnormal endogenous RB protein of 95 kDa (p95) that is located mainly in the cytoplasm. This protein was identified by antibodies recognizing several different RB epitopes, but not by one directed solely against the C terminus, suggesting C-terminal truncation. This conclusion was supported by analysis of mRNA and genomic DNA, which revealed that a transcriptionally active RB allele had a deletion of exons 21-27. In contrast to normal RB protein, this truncated protein was not phosphorylated and did not bind to the large tumor (T) antigen encoded by simian virus 40. We previously reported that introduction of normal RB protein into Saos-2 cells suppressed their neoplastic phenotype, indicating functional inactivation of their endogenous RB genes. These results provide an initial step to elucidate domains crucial to the cancer-suppression function of RB protein; its C-terminal portion is evidently important for this activity.
 ...
PMID:C-terminal truncation of the retinoblastoma gene product leads to functional inactivation. 168 60


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>