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 induction of WAF1 gene expression after the treatment with the anticancer agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU; nimustine hydrochloride) was studied in two human glioblastoma cell lines: U-87MG, which bears the wild-type p53 gene, and T98G, which bears the mutant p53 gene. A marked accumulation of WAF1 was observed 3 h after ACNU treatment in both cell lines. The induction of WAF1 mRNA by ACNU was detected by northern blot analysis in these cells. Binding activity of p53 to a p53 consensus sequence increased after treatment in U-87MG cells but not in T98G cells. The existence of a p53-independent WAF1 induction pathway was supported by the apparent accumulation of WAF1 after ACNU treatment in the p53-null human osteosarcoma cell line Saos-2. These findings suggest that there are two possible pathways for WAF1 induction: the p53-dependent pathway through the p53-responsive element and the p53-independent pathway through other elements.
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PMID:p53-independent WAF1 induction by ACNU in human glioblastoma cells. 953 48

A human osteosarcoma cell line, Saos-2, which is devoid of endogenous p53 gene, and clones of Saos-2 cells, which were transfected with wild type p53 or mutant p53 genes (123A, 143A, 175H and 273H), were observed for their surviving fraction after treatment with the commonly used anticancer drugs, cisplatin (CDDP), nimustine (ACNU), adriamicin (ADR) and bleomicin (BLM). The transfectants of the mutant 143A, 175H and 273H were significantly more resistant to CDDP than the transfectant of pOPI3 (expression plasmid only). The transfectants of the wild type p53 and mutant 123A were significantly more sensitive to ACNU than the transfectant of pOPI3. The transfectant of mutant 123A was more sensitive to ADR than the transfectant of pOPI3. There was no significant difference in sensitivity to BLM between Saos-2 and all kinds of transfectants. Thus the sensitivity of the cells to anticancer drugs varied with the mutation point of the p53 gene.
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PMID:Sensitivity of anticancer drugs in Saos-2 cells transfected with mutant p53 varied with mutation point. 956 97