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)

Potential cis-acting regulatory elements of the human platelet derived growth factor-B (PDGF-B) gene were identified by DNase I hypersensitive site mapping. The transcription unit was examined for the presence of hypersensitive sites in chromatin DNA isolated from human term placental cytotrophoblasts, human placental fibroblasts, the JEG-3 choriocarcinoma cell line and the U2-OS osteosarcoma cell line. A number of cell type-specific hypersensitive sites were identified, all within the 1st intron. Transient transfection of JEG-3 cells with CAT constructs containing regions of the c-sis 1st intron linked to the basal c-sis promoter identified a cell type-specific positive regulatory activity within the intron, composed of at least two distinct elements. One element appeared to be specific for JEG-3 cells, while the other was also active in U2-OS cells. The overall positive regulatory activity of the 1st intron region was specific for JEG-3 cells, but did not function as a classically defined enhancer, as it was orientation-dependent (unless stably integrated into chromatin DNA). In addition, the activator appears to require interaction with the c-sis promoter, as little or no activation was seen when either the SV40 or human beta-globin promoters were substituted for the c-sis promoter. The 1st intron also contained a negative regulatory element, which was specific for U2-OS cells and silenced an abnormally high basal c-sis promoter activity in these cells. The complexity of the transcriptional control of the PDGF-B gene is discussed.
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PMID:Expression of the human PDGF-B gene is regulated by both positively and negatively acting cell type-specific regulatory elements located in the first intron. 202 39

It has been reported that DNA of SV40, a virus of Asian macaques that is tumorigenic for rodents and can transform human cells in vitro, is present in pleural mesotheliomas and in several other cancers. To verify these observations, we tested paraffin sections from mesothelioma tissues of 50 patients for SV40 DNA using PCR with two separate sets of primers. The analytic sensitivity for detection of SV40 DNA was 1-10 genome copies. We also tested the specimens for beta-globin by PCR to assess the suitability of the specimen DNAs for amplification. beta-Globin amplification was detected in 48 of the 50 specimens, but SV40 DNA was not detected in any tumors, with either of two SV40 primer sets. Furthermore, sera from 34 additional patients with mesothelioma, 33 patients with osteosarcoma (another cancer reported to be SV40-related) and 35 controls were tested for SV40 antibodies by a plaque neutralization assay. The serological data, like the DNA results, did not support an association of SV40 with mesothelioma or with osteosarcoma; antibodies to SV40 were detected in three mesothelioma patients, in one osteosarcoma patient, and in one control. These findings call into question the association of SV40 with mesothelioma.
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PMID:Simian virus 40 and pleural mesothelioma in humans. 878 45

To investigate the functional differences between estrogen receptor (ER) alpha and beta subtypes, we studied the expression and the transcription stimulating activities of these receptors. RT-PCR has demonstrated that ER alpha is expressed at a high level in MCF-7 cells derived from human breast cancer. Both ER alpha and ER beta were expressed at a lower level in HOS-TE85 and Saos2 cells derived from human osteosarcoma. Chloramphenicol acetyltransferase reporter assay detected the transcriptional activation by the endogenous receptor only in MCF-7 cells. Agonistic effect of tamoxifen was observed as strong as that of 17beta-estradiol on ERE activation in MCF-7 cells at the concentration of 10(-7) M when ERE-containing reporter is constructed with beta-globin promoter. The effect of tamoxifen was not apparent when the reporter was constructed with thymidine kinase promoter, suggesting that the differential gene activation between tamoxifen and estrogen may take place depending upon ERE-promoter context. Agonistic activity of tamoxifen was also detected in COS-7 and Saos-2 cells, but not in HEC-1 cells derived from human endometrial carcinoma via exogenously expressed ER. Interestingly, this effect was ER alpha specific. Thus, we demonstrate that agonistic effect of tamoxifen depends on the cell type, ERE-promoter context, and ER subtype. These parameters would explain at least a part of the tissue specific effects of antiestrogens in vivo.
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PMID:Agonistic effect of tamoxifen is dependent on cell type, ERE-promoter context, and estrogen receptor subtype: functional difference between estrogen receptors alpha and beta. 922 41

The ability to overexpress physiologically important proteins in cultured mammalian cells after delivering the encoding mRNAs could have important applications for analyzing their in vivo functions. To explore the potential of this approach, urokinase-type plasminogen activator receptor (uPAR), a membrane protein extensively modified post-translationally, was selected. The uPAR-encoding mRNAs, containing different 5' and 3' untranslated regions (UTR) were tested in cultured human osteosarcoma (HOS) cells following a cationic lipid-mediated delivery. The most effective structure was the capped and polyadenylated transcript containing Xenopus beta-globin 5' and 3' UTRs. Delivering this mRNA to HOS cells resulted in a significant increase of uPAR expression in 89% of the cells, measured by flow cytometry. Using a radioligand binding assay, the increase in functional uPAR levels was found to be up eight- to 11-fold between 8 and 48 h and up three-fold at 72 h after delivery. A similar increase in uPAR levels was achievable in a number of mammalian cell lines. Surprisingly, poly(A)-tailed mRNA leading to a uPAR production highest in magnitude and duration did not demonstrate increased intracellular stability compared with other tested mRNAs. Thus, the exceptional translational performance is not likely the result of an increased mRNA half-life. These results demonstrate that, after delivery of selected mRNAs into mammalian cells, immediate and significant overexpression of a post-translationally modified protein is achievable.
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PMID:Overexpression of urokinase receptor in mammalian cells following administration of the in vitro transcribed encoding mRNA. 1045 12

Intra-operative autologous blood recovery offers many advantages. However, blood salvage during cancer surgery is of limited use due to the potential presence of circulating tumour cells. It was the aim of this study to show that intra-operative salvage blood can be freed of cells and cellular DNA after leucoreduction by filtration and irradiation of washed blood. Known amounts of tissue culture derived from carcinoma, melanoma and osteosarcoma were added to whole blood bags. This mixture was then submitted to washing, leucoreduction and irradiation. Samples were studied stepwise in relation to the integrity and size of DNA by the polymerase chain reaction (PCR). After filtration and irradiation, PCR targeting the beta-globin gene (268 bp amplicon) was negative. Our results were corroborated by studying plasma samples added with tumoural cells. Using PCR methodology, we showed the absence of DNA from cells in experimentally contaminated blood and plasma bags after filtration and irradiation. This experimental study is an effort to ensure the safety of intra-operative autologous transfusion.
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PMID:Molecular evidence of tumour cell removal from salvaged blood after irradiation and leucocyte depletion. 1676 3

Low-grade osteosarcoma is a rare variant of osteosarcoma. Although malignant, it must be distinguished from conventional osteosarcomas because of its excellent prognosis. Numerous published papers have described the expression of HER2/neu oncogene in osteosarcoma as a poor prognostic factor; however their results are discordant. To address the expression of HER2/neu and to validate the assessment methods of amplification of the HER2/neu oncogene, the authors have employed quantitative real-time PCR and fluorencent in situ hybridization analysis (FISH) in 21 low-grade osteosarcomas. We calculated the quantification of HER2/neu oncogene amplification as the ratio of measured HER2/neu gene/beta-globin reference gene in real-time PCR. All 21 cases had amplified signals in the quantitative real-time PCR. However, in the FISH analysis, HER2/neu oncogene amplification was only identified in 26% (5/19). The exact reasons for the discordance between these two methods are unknown; however, variable histological features might play a potential role. In conclusion, as our study showed amplification of HER2/neu oncogene in low-grade osteosarcoma, we assume that expression of HER2/neu is not a poor prognostic factor in low-grade osteosarcoma.
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PMID:Quantitative assessment of HER2/neu expression by real-time PCR and fluorescent in situ hybridization analysis in low-grade osteosarcoma. 1520 72