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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Simian virus 40 (SV40) is an oncogenic virus which induces tumors in hamsters and transforms human cells in tissue culture. Between 1955 and 1963, polio vaccines and adenovaccines were contaminated with SV40; therefore, millions of people were exposed to this oncogenic virus. The SV40 proteins responsible for in vivo oncogenesis and in vitro cell transformation are encoded by the early region of the virus. These proteins are called T (tumor) antigens (Tags), because animals with tumors induced by SV40 have antibodies against these viral proteins. Recently, we and other research laboratories have found SV40 in specific types of human tumors: mesothelioma, ependymoma and choroid plexus tumors, osteosarcoma and sarcoma. The same tumor types will develop in hamsters which have been injected systemically with SV40. SV40 causes cell transformation in tissue culture and tumors in animals, because SV40 Tag binds and inactivates the cellular tumor suppressor gene products, Rb and p53. We found that SV40 Tag binds p53 and Rb in human mesotheliomas, possibly contributing to the malignant phenotype.
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PMID:The biological activities of simian virus 40 large-T antigen and its possible oncogenic effects in humans. 968 8

Pleural mesotheliomas and osteosarcomas develop in hamsters injected intracardially with SV40. Using primers specific for the RB-pocket binding domain of SV40 we analysed with the polymerase chain reaction frozen specimens from 48 human mesotheliomas and 145 human bone tumours. We found that 60% of human mesotheliomas and 33% of human bone tumours contained SV40-like DNA. Immunostaining, Western blot and RNA in situ hybridization experiments revealed SV40 Tag expression in human mesotheliomas. Osteosarcomas were not studied for Tag expression because not enough material was available. Finally, antibodies anti-Tag were detected in the sera collected from patients with mesothelioma. These data indicate that SV40, or a closely related virus, is/are present in human mesothelioma and osteosarcoma.
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PMID:Evidence for and implications of SV40-like sequences in human mesotheliomas and osteosarcomas. 977 23

Mesotheliomas are pleural-based tumours mainly associated with asbestos exposure (70% of cases) and the incidence is still raising. Recently, a possible viral connection was reported and 60% of mesotheliomas were demonstrated to contain and express SV40-like DNA sequences. In this study, the presence of SV40-like DNA sequences were investigated in mesotheliomas (15 tissue samples and six cell lines) and in 63 additional bronchopulmonary carcinomas, one parietal osteosarcoma and non-malignant lung samples as well as in organizing pleuritis (8). Finally, 163 samples were analysed by the polymerase chain reaction (PCR) with a set of primers PYV.for and PYV.rev to amplify a 173 bp region of the SV40 Tag. and a 179 bp region JC virus (JCV) as well as a 182 bp region BK virus (BKV). PCR amplification and hybridization with a probe specific for SV40 Tag revealed that 47.6% of mesotheliomas, 28.6% of primary bronchopulmonary carcinomas and 16% of non-neoplasic lung diseases contained SV40-like DNA sequences. No statistically significant difference in the occurrence of these DNA sequences was found between malignant mesothelioma and bronchopulmonary carcinoma. However, a significantly higher number of mesothelioma cases exhibited SV40- like DNA sequences in comparison with non-malignant pleural and pulmonary tissues. The DNA sequences were not related to BK and JC virus sequences. These results indicate that SV40-like DNA sequences are present in mesotheliomas as well as in bronchopulmonary carcinomas and non-malignant pleuropulmonary diseases.
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PMID:Detection of SV40-like DNA sequences in pleural mesothelioma, bronchopulmonary carcinoma and other pulmonary diseases. 977 36

Mature adult mice of the C57BL/6-TgN(Amy1TAg)501Knw transgenic mouse lineage, 501, containing a liver alpha-amylase promoted-SV40 Tag hybrid gene, routinely develop SV40 Tag-induced metastatic osteosarcomas. This form of alpha-amylase was known to be expressed in the liver, salivary glands, pancreas, and fat. Cells in the normal rib adjacent to the periosteum also express alpha-amylase suggesting that transgene expression is correctly targeted to generate osteosarcomas. 501 mice express SV40 Tag in the salivary glands but do not develop abnormalities in these organs by the time of their death from SV40-induced osteosarcomas. Mice of the C57BL/6 strain make a strong and effective anti-tumor immune response to SV40 Tag immunization. However, immunization of 501 mice with SV40 Tag early in life does not alter or prevent SV40 Tag-induced osteosarcomagenesis. 501 mice mount a significantly less effective cytotoxic T-lymphocyte response following SV40 Tag immunization while 501 osteosarcoma-derived cells are fully susceptible to SV40 Tag-specific T-cell lysis. This suggests that partial tolerance, not loss of antigen presentation by tumor cells, characterizes this mouse model of endogenous bone tumor development. To determine whether the immune recognition of endogenous SV40 Tag could influence tumorigenesis, the metastatic potential and time of death from tumor was investigated in CD4-null mutant 501 mice and beta-2 microglobulin-null mutant 501 mice. The size and number of metastases in these strains and longevity of these strains varied. We suggest that components of both the innate and adaptive immune response control tumor appearance and progression.
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PMID:Expression and immune recognition of SV40 Tag in transgenic mice that develop metastatic osteosarcomas. 1095 95

Simian virus 40 (SV40) is a dsDNA polyomavirus that induces osteosarcomas and mesotheliomas in hamsters and transforms many types of cells in tissue culture, including human cells. Osteosarcoma is a bone malignancy with multiple molecular lesions underlining progression from normal bone to osteosarcoma. Recent investigations have identified SV40 DNA sequences in osteosarcomas, suggesting that SV40 may contribute to tumor development. However, these studies also demonstrated that geographical differences exist between SV40 and tumor association. Our study analyzed 46 frozen German tumor specimens (42 osteosarcomas and 4 sarcomas initially suspected to be osteosarcomas) for the presence of SV40 DNA sequences by using PCR. Two different primer sets amplifying a 573 bp region of SV40 Tag gene with the complete intron sequence (SV.for 2/SV.rev) and a 172 bp region with no intron sequence (SV.5/SV.6) were used. DNA sequencing analysis verified the results. No SV40 sequences could be detected using the primer set SV.for 2/SV.rev, while 2 out of 42 osteosarcoma specimens and 1 out of 4 poorly-differentiated tumor specimens contained SV40 sequences, using the primer set SV.5/SV.6. From one of these two positive osteosarcomas, multiple tumor biopsies taken at different times during the dissection, including metastasis, tested positive for SV40. These results indicated that in Germany, only rare osteosarcomas can be linked to SV40. These results support previous findings involving geographical differences in the presence of SV40. Finally, the specific detection of SV40 sequences with multiple specimens from one of the two patients and the absence of SV40 sequences in all other samples underscores the specificity and reproducibility of this investigation and ruled out PCR contamination.
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PMID:SV40 sequences in human osteosarcoma of German origin. 1120 1

The role of Gemin5 in alternative mRNA splicing, tumor cell motility, and proteomic instability was investigated. Isotope Capture Affinity Tag proteomic analysis was conducted on MDA-MB-435 tumor cells transfected with either a control vector (C-100) or the Nm23-H1 metastasis suppressor (H1-177). Ingenuity pathway analysis revealed that RNA posttranscriptional processing was the most prominent class of differentially expressed proteins. Within this category, overexpression of Acinus1, Poly(a) binding protein, HNRPA2B1, Bop1, and Gemin5 was confirmed in less metastatic H1-177 cells. Overexpression of the latter four proteins was also observed in the lower metastatic antisense Ezrin transfectant of a murine osteosarcoma model system, confirming the general relevance of the trends. Gemin5, a component of the spliceosomal complex, was chosen for further study. Analysis of global mRNA splicing by SpliceArray chips revealed that 16 genes were differentially spliced in C-100 compared with H1-177 cells; transient transfection of gemin5 into C-100 cells restored the splice pattern to that of H1-177 cells. Alternative splicing patterns for the engulfment and cell motility 1 and thrombospondin 4 genes were confirmed by semiquantitative reverse transcription-PCR. Gemin5 overexpression coordinately reduced C-100 cell motility by 50%, and siRNA-mediated reduction of Gemin5 expression increased the motility of H1-177 cells by 2-fold (P < 0.004). The data provide the first demonstration that alterations in the expression of a spliceosome protein can effect both specific splicing events and tumor cell motility. The data also show that changes in mRNA splicing patterns accompany metastatic progression, which may contribute to proteome instability.
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PMID:Alterations in Gemin5 expression contribute to alternative mRNA splicing patterns and tumor cell motility. 1824 61