A novel selenonucleoside suppresses tumor growth by targeting Skp2 degradation in paclitaxel-resistant prostate cancer.

Prostate cancer (PC) is the most common disease in men over age 50, and its prevalence rate has been gradually increasing since 1980. Taxane-derived anticancer agents are the primary agents used to treat metastatic prostate cancer patients; however, the side effects and acquired drug resistance limit the success of these therapies. Because there is no specific treatment for paclitaxel-resistant prostate cancer, it is necessary to develop new targets and therapeutic strategies to overcome the acquired resistance. In this study, the antitumor activity of a novel selenonucleoside (4'-selenofuranosyl-2,6-dichloropurine, LJ-2618), a third-generation nucleoside, and its plausible mechanisms of action in paclitaxel-resistant prostate cancer (PC-3-Pa) cells were investigated. The established PC-3-Pa cells exhibited over 100-fold resistance against paclitaxel compared to the paclitaxel-sensitive PC-3 cells. LJ-2618, however, effectively inhibited the proliferation of both cell lines with similar IC50 values in vitro. In PC-3-Pa cells, the activated PI3K/Akt signaling pathway was suppressed by LJ-2618 treatment. In addition, Skp2 was found to be over-expressed in paclitaxel-resistant cells, and the transfection of Skp2 siRNA recovered the sensitivity of paclitaxel in PC-3-Pa cells. Furthermore, LJ-2618 significantly down-regulated Skp2 expression in PC-3-Pa cells by promoting degradation and inducing destabilization of Skp2, which triggers G2/M cell cycle arrest. In a xenograft mouse model implanted with PC-3-Pa cells, LJ-2618 (3 or 10 mg/kg) effectively inhibited tumor growth with the enhancement of Skp2 degradation and induction of p27 expression in tumor tissues. These findings suggest that LJ-2618 may have potential for overcoming paclitaxel resistance via promoting Skp2 degradation and stabilizing p27 expression in PC-3-Pa cells. Therefore, the novel selenonucleoside LJ-2618 may lead to the development of a new treatment strategy for patients with paclitaxel-resistant, castration-resistant prostate cancer.

Usability of the Thera-Band® to improve foot drop in stroke survivors.

BACKGROUND: Stroke survivors show "foot drop", dragging their toes on the ground in the swing phase of gait. Ineffective ankle dorsiflexion may result in an abnormal gait pattern. OBJECTIVE: The purpose of this study was to investigate the effect of ankle Thera-Band® use on gait patterns in stroke survivors. METHODS: Gait data were collected in eight subjects who had had strokes using gait analysis system, both with and without the Thera-Band®. The following dependent variables of gait parameters were analyzed: velocity, cadence, step length, stride length, single support time, and double support time. RESULTS: There were significant improvements in gait velocity, cadence, stride length, and double support time in those who used the Thera-Band® compared to those who did not (p <  0.05). However, there were no significant differences in step length or single support time (p >  0.05). CONCLUSIONS: The results show that ankle Thera-Band® use may have a positive effect in improving gait parameters by increasing the ankle stability in stroke survivors with foot drop. Its usefulness in the rehabilitation of foot drop in stroke survivors needs to be further investigated.