Anticancer research
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Anticancer research · Jan 1999
A novel hydroxamic acid compound, BMD188, demonstrates anti-prostate cancer effects by inducing apoptosis. I: In vitro studies.
Prostate cancer is the most frequently diagnosed malignancy in the Western countries. Apoptosis-targeted drug development could represent a specific and effective weapon against the disease (Tang and Porter, 32: 284-293, 1997). We previously demonstrated that the arachidonate 12-lipoxygenase and its metabolic products could function as survival factors for many solid tumors (Tang et al., Proc. Natl. Acad. Sci. USA 93: 5241-5246, 1996; Tang and Honn, J. Cell. Physiol. 172: 155-170, 1997). ⋯ The data presented here suggest that these novel cyclic hydroxamic acid compounds, via induction of apoptotic death, may find potential clinical applications in the treatment of human prostate cancers.
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Anticancer research · Jan 1999
A novel hydroxamic acid compound, BMD188, demonstrates anti-prostate cancer effects by inducing apoptosis. II: In vivo efficacy and pharmacokinetic studies.
In the preceding paper, we demonstrated that, BMD188 [cis-1-hydroxy-4-(1-naphthyl)-6-octylpiperidine-2-one], a newly synthesized cyclic hydroxamic acid compound, induces potent apoptotic death of prostate cancer cells in vitro. In this project, we studied the in vivo pharmacokinetic behavior and anti-tumor efficacy of this novel compound. ⋯ Collectively, the preceding in vitro and the current in vivo studies suggest that BMD188 and its analogs may find clinical applications in the treatment of prostate cancer patients by inducing apoptotic death of prostate cancer cells.
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Anticancer research · Jan 1999
Antitumor activity of titanocene dichloride in xenografted human renal-cell carcinoma.
Titanocene dichloride [(C5H5)2TiCl2] is a new-developed organometallic antitumor agent which is currently being investigated in clinical trials of phases I and II. In the present study, it was tested for antitumor activity in human renal tumors either growing as monolayers in vitro or as xenografts in athymic mice. For comparison, approved cytostatic drugs (in vitro, vinblastine and 5-fluoro-2'-deoxyuridine; in vivo, cyclophosphamide, vinblastine, and 5-fluorouracil) were administered in vitro and in vivo at equivalent or equitoxic dose levels, respectively. ⋯ Titanocene dichloride was again significantly active in the KTCTL-1M carcinoma xenograft and caused relative growth reductions by 50-65%. In the case of the MRI-H 121 renal sarcoma xenograft, however, the organometallic compound showed an only marginal activity which was surpassed by cyclophosphamide, vinblastine and 5-fluorouracil, all three drugs inducing significant relative growth inhibitions by 50-88%. These results confirm a significant and remarkable antitumor activity of titanocene dichloride in three out of four human renal tumors xenografted to athymic mice and suggest that clinical studies of phase II with titanocene dichloride towards renal-cell carcinoma in human patients should be done in the near future.