Sulfated alginate oligosaccharide exerts antitumor activity and autophagy induction by inactivating MEK1/ERK/mTOR signaling in a KSR1-dependent manner in osteosarcoma.

Alginate oligosaccharide (AOS) has the function to inhibit tumor progression and the sulfated modification can enhance the antitumor activity. To date, the function and mechanism of sulfated AOS (AOS-SO4) in tumors remain largely elusive. We prepared AOS by the enzymatic degradation of alginate, collected AOS-SO4 by sulfating following the canonical procedure. Using these materials, in vitro assays showed that both AOS and AOS-SO4 elicited antitumor effects in osteosarcoma cells. Sulfated modification significantly enhanced the antitumor activity. In addition, AOS-SO4 had obvious effects on cell cycle arrest, apoptosis, and autophagy induction in vitro and in vivo. Mechanistically, we observed that AOS-SO4 treatment triggered proapoptotic autophagy by inhibiting MEK1/ERK/mTOR signaling. The ERK activator reversed AOS-SO4-induced autophagy. More importantly, we found that KSR1 interacted with MEK1 and functioned as a positive regulator of MEK1 protein in osteosarcoma cells. High KSR1 expression was significantly associated with poor survival in osteosarcoma patients. Together, these results suggest that AOS-SO4 has a better antitumor effect in osteosarcoma by inhibiting MEK1/ERK/mTOR signaling, which is KSR1-dependent; thus, AOS-SO4 can be a new potential therapeutic candidate for the treatment of osteosarcoma.

Effects of antidepressants on P2X7 receptors.

Antidepressants including paroxetine, fluoxetine and desipramine are commonly used for treating depression. P2×7 receptors are member of the P2X family. Recent studies indicate that these receptors may constitute a novel potential target for the treatment of depression. In the present study, we examined the action of these antidepressants on cloned rat P2×7 receptors that were stably expressed in human embryonic kidney (HEK) 293 cells by using the whole-cell patch-clamp technique, and found that paroxetine at a dose of 10µM could significantly reduce the inward currents evoked by the P2×7 receptors agonist BzATP by pre-incubation for 6-12 but not by acute application (10µM) or pre-incubation for 2-6h at a dose of 1µM, 3µM or 10µM paroxetine. Neither fluoxetine nor desipramine had significant effects on currents evoked by BzATP either applied acutely or by pre-incubation at various concentrations. These results suggest that the sensitivity of rat P2×7 receptors to antidepressants is different, which may represent an unknown mechanism by which these drugs exert their therapeutic effects and side effects.

Health-related quality of life in patients with spinal metastases treated with or without spinal surgery: a prospective, longitudinal study.

BACKGROUND: The objective of this study was to determine whether surgery for patients with spinal metastases could improve the quality of remaining life and prolong survival. METHODS: In total, 96 patients who had spinal metastases were recruited from Changzheng Hospital at the Second Military Medical University in Shanghai, China, over the period from July 2007 to June 2009. The patients received treatments with or without spinal surgery (surgery group, n=46 patients; nonsurgery group, n=50 patients), and all patients received adjuvant therapies according to their original cancer and individual conditions. Patients' quality of life (QOL) was assessed at 5 time points-at the initial diagnosis (baseline) and at 1 month, 3 months, 6 months, and 9 months of follow-up-using the Functional Assessment of Cancer Therapy-General QOL questionnaire. Information on survival also was collected. RESULTS: Sixty-seven of 96 patients completed all 5 follow-up assessments, including 33 patients in the surgery group and 34 patients in the nonsurgery group. The other 29 patients died within 9 months after the initial diagnosis. At the end of the study (June 2009), 22 patients (47.8%) remained alive in the surgery group, and with 16 patients (32%) remained alive in the nonsurgery group. The surgery group had significantly higher total QOL scores, physical well being scores, emotional well being scores, and functional well being scores than the nonsurgery group over the 9-month assessment period. There was no statistically significant difference in survival between the 2 groups (P=.056). CONCLUSIONS: The current results indicated that surgical treatment greatly improved and maintained the QOL of patients who had spinal metastases over the 9-month assessment period and that surgery is an effective treatment for spinal metastases.