Showing papers by "Betty Soliven published in 1995"
TL;DR: Suramin can be safely administered without adaptive control, and suramin on this schedule may exhibit significant activity against hormone-refractory metastatic prostate cancer, and based strictly on toxicity considerations, it is recommended that a day-1 dose of 1,440 mg/m2 be used in subsequent clinical trials, with a maximum of three cycles.
Abstract: PURPOSESuramin is a promising agent for the treatment of hormone-refractory metastatic prostate cancer. However, questions about the relationship of severe neurotoxicity to sustained peak plasma concentrations greater than 300 micrograms/mL raised concerns that this drug could not be safely administered without adaptive control. To test the adaptive-control hypothesis, we designed a phase I study that relied on clinical end points, using a fixed dosing scheme that did not rely on adaptive control.PATIENTS AND METHODSIn a phase I dose-escalation study using fixed dosing without adaptive control, gradually decreasing doses of suramin were administered to 63 patients on days 1 (loading dose), 2, 8, and 9 of a 28-day cycle. Fifty-four patients with hormone-refractory metastatic prostate cancer and nine patients with other solid tumors have been treated.RESULTSDoses of 400 mg/m2 to 2,080 mg/m2 on the first day have been administered. The mean peak plasma concentration following the loading dose at a dose level...
46 citations
TL;DR: This work studied the effects of AA and other fatty acids on whole cell K+ currents of cultured rat oligodendrocytes using the patch-clamp technique and demonstrated an additional mechanism for AA-induced signaling through modulation of K+ conductances leading to membrane depolarization.
Abstract: Arachidonic acid (AA) and its metabolites play a dual role as intracellular second messengers and as transcellular mediators of neural activity. We have previously shown that AA increases cytosolic Ca2+ in oligodendrocytes. In this work, we studied the effects of AA and other fatty acids on whole cell K+ currents of cultured rat oligodendrocytes using the patch-clamp technique. We found that 1) AA decreased the current amplitudes of both the inwardly rectifying K+ current (IKir) and the outward K+ currents (IKo) resulting in membrane depolarization; 2) AA also induced IKo current inactivation/blocked state; 3) AA appeared to act directly on K+ channels and not indirectly via its metabolic products, activation of protein kinase C, or by generation of oxygen free radicals. We have thus demonstrated an additional mechanism for AA-induced signaling in oligodendrocytes, i.e., via modulation of K+ conductances leading to membrane depolarization. The latter has been shown to influence protein phosphorylation and perhaps other important functional output of oligodendrocytes.
40 citations