Comparative inhibition of prostate cell invasion by conformationally flexible and constrained bis(2,6-dioxopiperazine)s

Inhibition of the migration of human prostate cancer PC-3 cells by a series of 18 conformationally flexible and constrained bis(2,6-dioxopiperazine)s including selected bis(morpholinomethyl) derivatives was investigated in vitro using the Matrigel invasion assay. The anti-invasion effects were compared to the cytotoxic effects of these experimental drugs. The parent conformationally mobile ICRF-159 (razoxane) and its dextrorotatory isomer ICRF-187 (dexrazoxane) inhibited invasion at concentrations that were at least 19-fold lower than their cytotoxic concentrations. This indicates that the anti-invasion effect was achieved independent of cytotoxicity. Seven conformationally constrained compounds were found to have no appreciable anti-invasive activity. Generally, the morpholinomethyl pro-drug derivatives of seven of the dioxopiperazines, exhibited either anti-invasive or cytotoxic activities that were reduced or unchanged relative to the parent molecules. In summary, certain bis(2,6-dioxopiperazine)s exhibit a promising and selective anti-invasion effect in human prostate cells. This activity seems to require a flexible linker allowing for multiple conformational possibilities of the dioxopiperazine rings.     

The consequences of disclosure: one hospital's response to the presence of an HIV-positive physician

Health care administrators are having to confront the many and complex problems associated with patient fears about the transmissibility of the HIV virus. Particularly acute are concerns that are raised when the physicians are HIV-positive or have AIDS. This article presents a case history of how one hospital handled the problems created by the announcement by one of its emergency room physicians that he was HIV-positive. The hospital's response--which included disclosure to the community, the full cooperation of the physician, provision of free counseling, and HIV testing--and the aftermath of this AIDS-related event are described. This case is discussed in relationship to the ongoing debate about the ethics and consequences of disclosure of the HIV status of health care workers.