Our recent data, both published and unpublished, strongly suggest that some HDACs are deregulated in endometrial selleckchem Rapamycin stromal sarcomas and other uterine tumors of mesenchymal origin. The therapeutic utility of vorinostat is supported by the fact that it has been recently approved by FDA for therapy of cutaneous T cell lymphoma. Moreover, vorinostat is used in clini cal trials in patients with other solid tumors, such as mesothelioma, medulloblastoma, prostate and thyroid cancer. Our in vitro and in vivo data suggest that vorinostat is an active drug potentially suitable for targeted treatment of uterine sarcomas. Methods Chemicals and cell lines All chemicals and media were purchased from Sigma, unless otherwise specified. Vorinostat was purchased from Alexis Biochemicals.

The human uterine sarcoma cell line MES SA, established by Harker et Inhibitors,Modulators,Libraries al, was purchased from ATCC. The original specimen was characterized as poorly differentiated uterine sarcoma and the cells were isolated Inhibitors,Modulators,Libraries after hysterectomy of a 56 years old Caucasian woman. It has been also shown that these cells are highly tumorigenic in nude mice. All experiments were performed Inhibitors,Modulators,Libraries according to local ethical guidelines. Drug formulation For in vitro experiments a 10 mM vorinostat stock solu tion was prepared with DMSO and stored at 20 C. Since it is well known that DMSO can cause different inflammatory reactions when injected intraperitoneally for a longer period of time, we wanted to avoid this sol vent for our in vivo experiments. Therefore, we prepared a solution of vorinostat in HOP b CD as already described by Hockly et al.

Briefly, vorinostat was dissolved in 5 molar equiva Inhibitors,Modulators,Libraries lents of HOP b CD in water, it was heated until fully dissolved, rapidly cooled on ice to room temperature and stored at 20 C. A fresh solution was prepared every week and administered to the mice by intraperitoneal injection in a total volume of approx. 300 ul, so that the final concentration for each animal was 50 mg/kg/day. In vivo experiments The animal experiments were approved by the Austrian ministry of education and science according to the regulations for animal experimentation. Athymic Nude Foxn1nu/nu mice used in the present study were purchased from Harlan. They were housed at 22 C at a constant light dark cycle and had free access to water and rodent chow.

Inhibitors,Modulators,Libraries All animals used in this study were kept under standardized, pathogen free living conditions in the animal facility no of our department. Twelve weeks old male mice were anesthe tized with Isofluran and 5 106 MES SA cells were injected subcutaneously into the right flank of the animal. Mice from a control group received placebo containing 300 ul of empty HOP b CD vesicles. Another group of mice received vorinostat dissolved in HOP b CD at a concentration of 50 mg/kg/ day.