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PMID:9041188
Nine human ovarian cancer cell lines that express wild-type (wt) or mutated p53 were used to evaluate the cytotoxicity induced by paclitaxel.
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PMID:9041188
The IC50 calculated in the five mutated p53-expressing cell lines was not different from the four wt p53-expressing cell lines.
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PMID:9041188
The introduction of wt p53, by using a temperature-sensitive mutant murine p53 or the human p53 under the control of a tetracycline-dependent promoter, did not change the cytotoxicity of paclitaxel as compared to mock-transfected cells.
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PMID:9041188
By using for each cell line the paclitaxel IC50, we found that these concentrations were sufficient to induce an increase in p53 levels in all of the four wt p53-expressing cells, whereas in the mutated p53-expressing cells, the levels were unaffected.
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PMID:9041188
This increase in p53 levels led to an increase in the mRNA and protein levels of p53 downstream genes (WAF1, GADD45, and bax).
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PMID:9041188
In none of the cell lines examined was paclitaxel able to induce apoptosis, evaluated by terminal deoxynucleotidyl transferase-mediated nick end labeling staining and filter binding assay at concentrations closed to the IC50.
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PMID:9041188
By increasing the concentration of paclitaxel in the filter binding assay, we could see fragmentation of DNA in the different cell lines.
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PMID:9041188
We conclude that the presence of p53 is not a determinant for the cytotoxicity induced by paclitaxel in human ovarian cancer cell lines.
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PMID:9041188
Differences in the activation of p53 downstream genes could be observed in wt versus mutated p53-expressing cells, but this does not account either for a differential induction of apoptosis or for a change in cytotoxicity induced by paclitaxel.
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PMID:14991574
Sulfamoylation of 2-methoxyestrone (2-MeOE1) was shown previously to enhance its potency as an anti-proliferative agent against breast cancer cells.
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PMID:14991574
We have examined the ability of a series of 2-methoxyestradiol (2-MeOE2) and 2-ethylestradiol (2-EtE2) sulfamates to inhibit angiogenesis in vitro.
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PMID:14991574
2-MeOE2 bis-sulfamate and 2-EtE2 sulfamate were potent inhibitors of human umbilical vein endothelial cell (HUVEC) proliferation with IC(50) values of 0.05 microM and 0.01 microM, respectively.
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PMID:14991574
A novel co-culture system, in which endothelial cells were cultured in a matrix of human dermal fibroblasts, was also used to assess the anti-angiogenic potential of these drugs.
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PMID:14991574
In this system endothelial cells proliferate and migrate through the culture matrix to form tubule structures.
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PMID:14991574
Whereas 2-MeOE2 (1.0 microM) caused a small reduction in tubule formation, both 2-MeOE2 bis-sulfamate (0.1 microM) and 2-EtE2 sulfamate (0.1 microM) almost completely abolished tubule formation.
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PMID:14991574
2-MeOE2 bis-sulfamate and 2-EtE2 sulfamate both induced BCL-2 phosphorylation, p53 protein expression and apoptosis in HUVECs.
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PMID:14991574
Microarray analysis of a limited number of genes known to be involved in the angiogenic process did not show any gross changes in cells treated with the 2-substituted estrogens.
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PMID:14991574
The sulfamoylated derivatives of 2-MeOE2 and 2-EtE2 are potent inhibitors of in vitro angiogenesis and both compounds should have therapeutic potential.
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PMID:15990222
Treatment failures result from resistance to chemotherapy in ovarian cancer.
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PMID:15990222
The effect of cisplatin and paclitaxel treatments on chemosensitivity was studied in ovarian cancer cells developed from a patient with stage IIIC disease.
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PMID:15990222
Cells (UL-3A, UL-3B) that recovered from cisplatin (Cis) and paclitaxel (Tax) treatments showed higher levels of p53, mdr-1 and chemoresistance than untreated controls.
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PMID:15990222
EC50 values of Cis and Tax for UL-3A clones were 7.2-34.6, average 20.9 microg/ml, while UL-3B clones ranged from 11.8-252.0 microg/ml, with a mean value of 73.2 microg/ml for Cis, and 260.0-4400.0 nM (mean 2555.0 nM) for Tax.
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PMID:15990222
Selection pressures during treatment may contribute to drug resistance.
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PMID:9231689
Tumors are thought to differ in their response to cytotoxic agents for a variety of reasons including cell cycle kinetics, degree of hypoxia, differential repair, and ability to survive when stressed.
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