Cytotoxicity and neurocytotoxicity of new marine anticancer agents evaluated using in vitro assays

Purpose: New classes of anticancer drugs, isolated from marine organisms, have been shown to possess cytotoxic activity against multiple tumor types. Aplidine, didemnin B, and isohomohalichondrin B (IHB), among the more promising antitumor candidates, have been evaluated in the present study on a comparative basis in terms of their antiproliferative activity and neurotoxic effects in vitro. Methods: Using a panel of different human, prostatic cancer cell lines (DU 145, PC-3 and LNCaP-FGC) the effects of Aplidine, didemnin B, and IHB on tumor cell proliferation were tested in a colorimetric (XTT) assay and compared with the effects of vincristine, vinorelbine, and Taxol. Under analogous in vitro conditions these drugs were also monitored for neurocytotoxic effects using a PC 12 cell line based model. Results: Didemnin B and - especially Aplidine were more effective in the inhibition of prostate cancer cell proliferation than vincristine, vinorelbine or Taxol at concentration levels between 5 and 50 pmol/ml. At these same concentrations, however, Didemnin B and Aplidine were also most potent in the in vitro neurotoxicity assays. IHB was found to exert even more potent antiproliferative activity (at concentration levels between 0.05 and 0.1 pmol/ml). However, neurotoxic effects were also found to be present at these levels. After drug withdrawal, the neurotoxic damage, inflicted by aplidine or IHB appeared to be more long lasting than after vincristine or vinorelbine exposure. Conclusions: These results point to high antiproliferative activity of aplidine and IHB in prostate cancer. At the same time, the data urge some caution in the clinical use of these agents because of potential neurotoxic side-effects. The use of a newly formulated Aplidine may involve a more favorable therapeutic profile

Valuing self-protection: income and certification effects for safe rooms

Survey data from Tulsa, Oklahoma residents are used to examine individual valuations of safe rooms. The study utilises two measures of individual valuations, the maximum willingness to pay (WTP) and willingness to accept (WTA) for safe rooms. The primary research questions are concerned with whether the willingness to pay measure exhibits income effects and whether certification standards make the safe room investment more desirable. The main findings can be summarised as follows. The mean willingness to pay for a safe room was $2,500. The value of certification by a national organisation increased willingness to pay for the safe room by$600 on average. There is no direct income effect in that respondents' stated willingness to pay does not bear a statistically significant relationship to reported income. There is evidence of a secondary income effect in that willingness to pay elicited from attendees of a suburban parade of homes was $731 higher than attendees of an urban parade of homes. A mortgage payment-based WTA measure yields mean valuations of the safe room more than three times higher than the lump sum WTP valuation.Safe room, willingness to pay, willingness to accept, valuation, certification,