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)

Previously, we have shown that the chicken anemia virus-derived VP3 ("apoptin") protein induces apoptosis in chicken mononuclear cells. Here, we report that apoptin also induces apoptosis in human osteosarcoma cells, regardless of whether they expressed wild-type, mutant p53, or no p53 at all. Moreover, the nuclear location of apoptin appears to be important for its optimal induction of apoptosis. The fact that apoptin can induce p53-independent apoptosis in human tumor cells makes apoptin a potential candidate for treatment of frequently occurring types of cancer cells that do not contain functional p53.
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PMID:Apoptin, a protein derived from chicken anemia virus, induces p53-independent apoptosis in human osteosarcoma cells. 783 13

Immunohistochemical evaluation of 24 osteosarcoma using an anti-p53 protein monoclonal antibody (Moab p53-12) showed strong positive reaction in the nuclei of tumor cells in 14 osteosarcoma (58.3%). Many studies have proved that this overexpression of p53 protein in tumor cells is associated with mutation of the p53 gene. Contrast study with DNA flow cytometry made on osteosarcoma showed that most of the p53 strongly positive tumors have higher DNA Index value than negative or slightly positive ones, though no statistically difference existed between two groups. Southern blot hybridization of p53 gene was also made in osteosarcomas. 5 of 20 cases (20%) had the structural changes of p53 gene. 3 of them were part or whole deletion of the gene. 2 of them had the extra-band, indicating the rearrangement of the gene.
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PMID:[p53 antioncogene abnormal in osteosarcoma]. 784 79

The ability of the p53 protein to act as a sequence-specific transcriptional activator suggests that genes induced by p53 may encode critical mediators of p53 tumor suppression. Using a tetracycline-regulated p53 expression system and cDNA library subtraction procedure, we identified several p53-induced gene transcripts in human Saos-2 osteosarcoma cells that are novel on the basis of their size, regulation, and low abundance. Wild-type p53-dependent induction of these transcripts was observed in cells that are growth arrested by p53, as well as in cells that undergo apoptosis upon expression of an inducible wild-type p53 transgene. These results show that p53 activates the expression of numerous response genes and suggest that multiple effectors may play a role in mediating cellular functions of p53.
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PMID:Gene regulation by temperature-sensitive p53 mutants: identification of p53 response genes. 793 6

An oncogene product, p53, interacts with a simian virus 40-encoded T-antigen, which is an initiation protein for the viral DNA replication and also works as DNA helicase during elongation. Here we examine the interaction of p53 with cellular DNA helicase. A recombinant human wild type p53 fused with glutathione S-transferase was immobilized on glutathione-agarose as a ligand for affinity column. Hela cell extract was applied to the p53 column and the adsorbed proteins were eluted with buffers containing salt, 50% ethylene glycol, and glutathione. The ethylene glycol fraction contained a number of p53 binding proteins, and this fraction showed a DNA helicase activity measured by the displacement of DNA fragment from partially duplexed M13 DNA. The DNA helicase translocated in a 5'-to-3' direction on the single-stranded DNA using ATP as an energy source. The glutathione fraction that contained the p53 glutathione S-transferase fused protein also showed the same activity. The corresponding fractions from a control column carrying glutathione S-transferase showed only a trace amount of activity of DNA helicase. Therefore, the binding may be specific. Furthermore, an anti-p53 antibody column retained a p53-DNA helicase complex when the crude extracts of human placenta and of osteosarcoma cells were applied. These results indicate that p53 physically interacts with DNA helicase in vitro as well as in vivo.
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PMID:Anti-oncogene product p53 binds DNA helicase. 795 81

A family with an aggregation of adrenocortical carcinoma, rhabdomyosarcoma, osteosarcoma, and early onset breast cancer was referred to our laboratory. Because this aggregation was reminiscent of Li-Fraumeni syndrome, germ-line mutation of the p53 tumor suppressor gene was sought in the DNA of two affected members. The highly conserved regions spanning exons 5 to 8 of the p53 gene were screened by a previously validated denaturing gradient gel electrophoresis method. A single base pair deletion at codon 215 was detected in constitutional DNA of the two patients, and in the DNA extracted from an adrenocortical carcinoma tumor specimen of the propositus. This deletion is predicted to lead to the formation of a truncated p53 protein, a relatively rare event in Li-Fraumeni families. The spectrum of tumors observed in this family does not differ markedly from the spectrum observed in families with missense p53 mutations.
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PMID:Single base pair germ-line deletion in the p53 gene in a cancer predisposed family. 803 1

The expression of the p53 tumor suppressor gene protein was analyzed in 35 resected osteosarcomas, 5 resected osteochondromas, and in 2 human osteosarcoma cell lines by immunohistochemistry and flow cytometry. An abnormality in the expression of the p53 protein was found in 10(29%) of the 35 osteosarcomas. An overexpression of the p53 protein showed no correlation with the clinicopathological features, but the p53 protein staining pattern showed a tendency to be correlated with aggressive growth and the metastatic potential. Diffusely-stained tumors had a worse prognosis than those focally-stained. The relationship between the expression of p53 protein and the cell cycle was examined by flow cytometry. The maximum overexpression of p53 protein was detected in the cells at the S phase. These results indicated that the nuclear accumulation of the p53 protein, especially the staining pattern, was a potentially useful prognostic factor for osteosarcoma. However our study did not show any clear correlation between either the growth pattern or the morphological type of osteosarcoma and the immunohistochemical results for the p53 protein.
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PMID:[Expression of the p53 protein in human osteosarcoma]. 805 67

Second malignancies following treatment for osteosarcoma are unusual. Breast cancer occurring in patients with osteosarcoma has been reported following therapeutic chest irradiation. We now report three cases of breast cancer occurring in young women who were successfully treated for osteosarcoma. These women had not received therapeutic chest irradiation and in two of the three women there was no family history of breast cancer. Peripheral blood was available for study from one case. Of import, this case demonstrated a germline mutation in exon 7 of the tumor suppressor gene, p53. The mutation was detected by constant denaturing gradient gel electrophoresis and confirmed by DNA sequencing. In this particular patient, inactivation of the p53 gene may be involved in the development of both the first and second malignancy.
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PMID:Secondary breast cancer in patients presenting with osteosarcoma: possible involvement of germline p53 mutations. 805 7

Deletion of p53, which is an anti-oncogene located on chromosome 17p, was reported to be present at a high incidence in tumor cells of colorectal carcinoma, as well as osteosarcoma of the familial cancer syndrome. Mutations of the p53 gene were investigated in 59 surgical specimens of primary carcinomas of the urinary system from 57 patients, using the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis. The PCR products were sequenced using the dideoxy chain termination method or the DNA sequencer. The tumors examined were 20 transitional cell carcinomas (TCC) and 39 renal cell carcinomas (RCC). Mutations of the p53 gene were detected in 20.0% (4/20) of TCC and were present in 16.7% (1/6) of the tumors invading the muscular layer. In two patients with simultaneous double bladder TCC, the mutations were found only in the larger tumors. In RCC, mutations were detected in 7.7% (3/39) of patients. No significant correlation between the presence of the mutation and the clinicopathologic parameters was found in RCC except that the three tumors with p53 gene mutations were clear cell carcinomas. These results suggest that p53 gene mutations play a possible role in both carcinogenesis and progression of TCC, but the p53 gene mutations may not be significant in development of RCC.
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PMID:Mutations of the p53 gene in carcinomas of the urinary system. 810 52

We describe the isolation, growth-suppressing activity, and chromosomal localization of the human homologue of the murine growth-arrest-specific gene gas1. Overexpression of h-gas1 is able to block cell proliferation in the A549 lung carcinoma and the T24 bladder carcinoma cell lines. No effect was observed when h-gas1 was introduced into the osteosarcoma cell line SAOS-2 and into the adenovirus-type-5 transformed cell line 293. This finding is related to our previous evidence that simian virus 40-transformed NIH 3T3 cells are also refractory to murine gas1 overexpression, suggesting that the retinoblastoma and/or p53 gene products have an active role in mediating the growth-suppressing effect of gas1. We also show that h-gas1 is on chromosome 9q21.3-22.1, in a region considered to be a fragile site. Altogether, the results raise the possibility that h-gas1 may be a target for genetic alterations leading to its inactivation in tumor cells.
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PMID:Structure, function, and chromosome mapping of the growth-suppressing human homologue of the murine gas1 gene. 812 93

Codon 257 of the p53 gene is an extremely rare target for somatic mutations (accounting for only two of 1600 published mutations). We report here two constitutional mutations both affecting the second nucleotide of codon 257. A thymine to adenine transversion resulting in an amino acid change from leucine to glutamine was found in one proband who developed multiple independent malignant tumors (osteosarcoma, phyllodes tumor, soft-tissue sarcoma). Her mother died of early-onset breast cancer. In the other case, a deletion resulting in a frameshift in the C-terminal coding region of p53 was found in a woman who was diagnosed with breast cancer at age 34. This woman belongs to a family with features of Li-Fraumeni syndrome. In both cases, the p53 mutations identified in the proband was found in other members of the family. Codon 257, even if rarely mutated in somatic cells, may thus be an important target for germ-line mutations.
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PMID:Two germ-line mutations affecting the same nucleotide at codon 257 of p53 gene, a rare site for mutations. 813 27


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