Loss of 4.1N in epithelial ovarian cancer results in EMT and matrix-detached cell death resistance

Epithelial ovarian cancer (EOC) is one of the leading causes of death from gynecologic cancers and peritoneal dissemination is the major cause of death in patients with EOC. Although the loss of 4.1N is associated with increased risk of malignancy, its association with EOC remains unclear. To explore the underlying mechanism of the loss of 4.1N in constitutive activation of epithelial-mesenchymal transition (EMT) and matrix-detached cell death resistance, we investigated samples from 268 formalin-fixed EOC tissues and performed various in vitro and in vivo assays. We report that the loss of 4.1N correlated with progress in clinical stage, as well as poor survival in EOC patients. The loss of 4.1N induces EMT in adherent EOC cells and its expression inhibits anoikis resistance and EMT by directly binding and accelerating the degradation of 14-3-3 in suspension EOC cells. Furthermore, the loss of 4.1N could increase the rate of entosis, which aggravates cell death resistance in suspension EOC cells. Moreover, xenograft tumors in nude mice also show that the loss of 4.1N can aggravate peritoneal dissemination of EOC cells. Single-agent and combination therapy with a ROCK inhibitor and a 14-3-3 antagonist can reduce tumor spread to varying degrees. Our results not only define the vital role of 4.1N loss in inducing EMT, anoikis resistance, and entosis-induced cell death resistance in EOC, but also suggest that individual or combined application of 4.1N, 14-3-3 antagonists, and entosis inhibitors may be a promising therapeutic approach for the treatment of EOC.

Effects of oral calcium and active vitamin D on bone mineral density and balance function in senile osteoporosis patients / 中华老年医学杂志

Objective To investigate the effects of oral calcium and active vitamin D on bone mineral density and balance function in senile osteoporosis patients.Methods A prospective casecontrol study was conducted on 216 senile osteoporosis patients who met the inclusion criteria.Patients were given oral calcium and active vitamin D for 12 months.The data values of BMD,balance function,falls incidence and bone pain were compared before versus 6 and 12 months after treatment.Results There were significant differences in BMD of lumbar vertebrae and femur neck,static balance function assessed by the single-leg stance timed tests with closed eyes,dynamic balance function assessed by the Star Excursion Balance Test(SEBT) in directions of east,southeast,south and southwest(all P＜0.05).The incidence of falls was decreased 12 months after treatment as compared with pre-treatment(5.6％ vs.12.5％).The bone pain had no significant difference before versus after treatment(P＞0.05).Conclusions Oral calcium and active vitamin D could increase BMD,improve the balance function and decrease the risk of falls in senile osteoporosis patients.However,it has no significant improvement on bone pain within a short period.