idn-5109 has been researched along with Ovarian-Neoplasms* in 3 studies
1 review(s) available for idn-5109 and Ovarian-Neoplasms
Article | Year |
---|---|
Drug evaluation: Bay-59-8862.
Bayer Corp, under license from Indena SpA, is developing BAY-59-8862, a taxane synthesized from 14beta-hydroxy-10-deacetylbaccatin III, for the potential treatment of cancer. Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Evaluation, Preclinical; Female; Humans; Ovarian Neoplasms; Structure-Activity Relationship; Taxoids | 2004 |
2 other study(ies) available for idn-5109 and Ovarian-Neoplasms
Article | Year |
---|---|
A role for loss of p53 function in sensitivity of ovarian carcinoma cells to taxanes.
Loss of p53 function has been linked to increased responsiveness to taxane treatment of ovarian carcinoma in clinical studies. We recently reported that the acquisition of cisplatin resistance in an ovarian carcinoma cell line (IGROV-1) was associated with mutation of p53 and collateral sensitivity to paclitaxel. The increased sensitivity to paclitaxel of the cisplatin-resistant subline appeared to be pharmacologically relevant since it was reflected in an in vivo sensitization to taxanes. To investigate the cellular and molecular basis of this phenomenon, we performed a comparative study of cellular response to taxanes (paclitaxel and the novel analog IDN 5109) in the parental cell line, containing wild-type p53 and its cisplatin-resistant p53 mutant subline (IGROV-1/Pt1). IDN 5109 was included in this study because of its higher potency and efficacy compared with paclitaxel on both tumor systems. The pattern of cellular response of the two ovarian cell lines was different. In IGROV-1 cells, apoptosis was an early event consequent to a transient mitotic arrest. The cell death of IGROV-1/Pt1 cells was a somewhat slow and delayed event, following mitotic arrest and appearance of hyperploid cells. The increased cytotoxic effect of IDN 5109, compared with paclitaxel, was associated with more marked p34(cdc2) dephosphorylation in IGROV-1 cells and higher Bcl-2 phosphorylation in IGROV-1/Pt1 cells after 24 hr of treatment. In each cell line, these biochemical events were not correlated with parallel levels of mitotic cells. Attempts to reintroduce wild-type p53 in IGROV-1/Pt1 were unsuccessful. However, in other p53-deficient cells (osteosarcoma SAOS), taxane treatment was associated with hyperploid progression and the introduction of wild-type p53 resulted in a reduced sensivity. Although our approach does not allow definitive conclusions, these results suggest that loss of p53-dependent post-mitotic checkpoint results in a different time-course of taxane-induced cell death following DNA reduplication. These events, more evident after exposure to the potent analog IDN 5109, support the notion that the enhanced sensitivity of p53 mutant cells is closely related to the different mode of cell death. Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Bridged-Ring Compounds; Cell Cycle; DNA, Neoplasm; Female; Humans; Ovarian Neoplasms; Paclitaxel; Phosphorylation; Proto-Oncogene Proteins c-bcl-2; Taxoids; Tubulin; Tumor Cells, Cultured; Tumor Suppressor Protein p53 | 2001 |
IDN5109, a taxane with oral bioavailability and potent antitumor activity.
IDN5109 is a new taxane, derived from 14beta-hydroxy-10-deacetylbaccatin III, selected for its lack of cross-resistance in tumor cell lines expressing the multidrug resistant phenotype. Because, unlike paclitaxel, IDN5109 is a poor substrate for P-glycoprotein, we hypothesized that IDN5109 given p.o. could improve bioavailability compared with paclitaxel. Here, we studied the p.o. and i.v. pharmacokinetics of IDN5109 together with its antitumor activity. Using a high-performance liquid chromatography method, the bioavailability of IDN5109 was determined to be 48% after oral delivery. IDN5109 given p.o. was highly active against the two human ovarian carcinoma xenografts 1A9 and HOC18 (90-100% tumor regressions) and showed significant activity on the paclitaxel-resistant MNB-PTX1 xenograft (10% tumor regressions). The p.o. administration was as active as the i.v. route at doses reflecting the pharmacokinetic data. IDN5109 is the first taxane with good oral bioavailability and potent antitumor activity and represents a potential candidate for clinical investigation. Topics: Administration, Oral; Animals; Antineoplastic Agents; Biological Availability; Bridged-Ring Compounds; Dose-Response Relationship, Drug; Female; Humans; Mice; Mice, Nude; Ovarian Neoplasms; Paclitaxel; Taxoids | 2000 |