摘要:

Treatment of carcinoma cell lines with 15-deoxy-Δ12,14-prostaglandin J2(15d-PGJ2), a natural ligand of the peroxisome proliferator-activated receptor-&ggr;, has been reported to induce apoptosis and/or inhibit proliferation. In this study, we investigated the cytotoxic effect and the action mechanisms of 15d-PGJ2in a thyroid papillary cancer cell line, CG3. The results indicate that 15d-PGJ2caused cytotoxicity and increased the amount of intracellular reactive oxygen species (ROS) in these cells. Mitochondrial oxidative phosphorylation inhibitors (carbonyl cyanidem-chloro-phenylhydrazone, oligomycin, cyclosporin A and rotenone), NADPH oxidase inhibitor (diphenyleneiodonium), xanthine oxidase inhibitor (allopurinol) and NO synthase inhibitor (N-monomethyl-l-arginine acetate) did not reduce the generation of ROS. However, catalase,N-acetyl-cysteine and the iron chelator desferri-oxamine decreased the intracellular ROS of 15d-PGJ2-treated CG3 cells. Furthermore, 15d-PGJ2enhanced the accumulation of iron in the CG3 cells. These data suggest that 15d-PGJ2induces the generation of ROS by enhancing the accumulation of intracellular iron and that the increased oxidative stress may cause apoptosis of CG3 cells.

ISSN:0959-4973    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

New solubilizers, including Sorporol 230, Sorporol 120Ex, Aceporol 345-T, Aceporol 460 and Riciporol 335, as potential new delivery vehicles for paclitaxel were investigated, since recent studies have shown that the paclitaxel delivery vehicle Cremophor EL significantly alters the pharmacokinetics of paclitaxel. Cremophor EL and Tween 80 were used as a reference. As in the case of Cremophor EL, alteration of blood distribution of paclitaxel occurred in the presence of all tested vehicles. Also, no differences in the affinity of paclitaxel for the tested solubilizers was found during equilibrium dialysis experiments. The different vehicles could be distinguished by a different rate of esterase-mediated breakdown, which was correlated with the fatty acid content of the solubilizers. The activation of the complement cascade was less pronounced for all solubilizers, except Riciporol 335, compared to Cremophor EL. The strategies presented here provide the possibility to rapidly screen future candidate delivery vehicles with optimal characteristics for use as a solubilizer in clinical formulations of paclitaxel or other poorly water-soluble drugs.

ISSN:0959-4973    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Venlafaxine is an antidepressant which acts through the inhibition of the reuptake of norepinephrine and serotonin. Venlafaxine is active against neuropathic and chronic pain. We report the case of a 69-year-old woman who presented a paclitaxel-induced neuropathy. She presented paresthesias, pin pricks in both hands with functional impairment. Venlafaxine hydrochloride was introduced at 37.5 mg twice daily. The patient noticed a dramatic recovery of her symptoms within 2 days, with both reduction of the paresthesias and functional improvement. This is the first report of efficacious use of venlafaxine for the treatment of paclitaxel cumulative neurosensory toxicity.

ISSN:0959-4973    

出版商:OVID    

年代:2002

数据来源: OVID