Angiomotin-like 1 plays a tumor-promoting role in glioma by enhancing the activation of YAP1 signaling.

Angiomotin-like 1 (AMOTL1) is reportedly a pivotal tumor-associated protein that is strongly associated with the tumorigenesis of multiple malignant tumors. However, the issue of whether AMOTL1 plays a role in the tumorigenesis of glioma remains unclear. The aim of this work was to explore the possible relationship between AMOTL1 and glioma progression. Results demonstrated that high levels of AMOTL1 in glioma tissues were associated with a reduced survival rate in patients with glioma. Cellular functional assays revealed that silencing of AMOTL1 in glioma cell lines substantially decreased cell proliferation and invasion and increased cell apoptosis. Further investigation revealed that silencing of AMOTL1 inhibited the activation of yes-associated protein 1 (YAP1) and decreased the expression of YAP1 target genes. Reactivation of YAP1 reversed AMOTL1-silencing-induced antitumor effects, whereas inhibition of YAP1 abolished AMOTL1-overexpression-induced tumor-promoting effects in glioma cells. Silencing of AMOTL1 also retarded the growth of glioma cell-derived xenograft tumors in vivo. In conclusion, these findings suggested that AMOTL1 may exert a tumor-promoting function in glioma by enhancing the activation of YAP1 signaling. This work suggested AMOTL1 as a potential target for the development of antiglioma therapy.

Bone marrow-derived mesenchymal stem cells co-expressing interleukin-18 and interferon-ß exhibit potent antitumor effect against intracranial glioma in rats.

Bone marrow-derived mesenchymal stem cells (BMSCs) are promising gene vehicles for cancer gene therapy. In our previous study, we reported that BMSCs expressing interleukin (IL)-18 effectively inhibit the growth of glioma in rats. In the present study, we further detected the effect of BMSCs co-expressing IL-18 and interferon (IFN)-ß, both of which are immunostimulatory cytokines. BMSCs were genetically engineered to express IL-18 and IFN-ß by transfection of recombinant lentivirus-mediated gene transfer. Results showed that BMSCs co-expressing the two cytokines displayed more significant inhibition effect on glioma cell growth in vitro when compared with BMSCs solely expressing IL-18 or IFN-ß. Treatment of BMSCs co-expressing IL-18 and IFN-ß significantly prolonged the survival and inhibited tumor growth in a rat intracranial glioma model. Furthermore, these genetically engineered BMSCs remarkably promoted cell apoptosis, antitumor cytokine production and CD4+ and CD8+ T-cell infiltration in intracranial glioma tissues than BMSCs solely expressing IL-18 or IFN-ß. Results of the present study suggested that IL-18 and IFN-ß had a synergistic effect on glioma inhibition. Moreover, results provided evidence that delivery of IL-18 and IFN-ß by BMSCs may be an excellent and promising approach to develop an effective treatment protocol for glioma therapy.

[Changes of endothelial cell function and platelet activation in rabbit spinal cord with ischemia-reperfusion injury].

OBJECTIVE: To study the changes of vascular endothelial cell function and platelet activation in rabbit spinal cord following ischemia-reperfusion (I/R) injury and their roles in the spinal cord injury. METHODS: Rabbit spinal cord I/R injury models were established using Zivin method, and the changes in plasma NO and GMP140 levels were dynamically monitored after the injury. RESULTS: Plasma NO level increased significantly in the I/R group at the end of the ischemia, and reached the peak level at 2 h of reperfusion as compared to that in sham-operated group (P<0.01). Plasma NO level decreased at 6 h of reperfusion, but still significantly higher than the level in the sham-operated group (P<0.05). Plasma GMP140 underwent no significant changes in the sham-operated group, but significantly increased in the I/R group at the end of the ischemia, followed by gradual declination to the normal level at 2 h of reperfusion. CONCLUSION: Spinal cord I/R injury causes overexpressions of NO and GMP140, suggesting the involvement of endothelial cell injury and platelet overactivation in the pathological process and repair of spinal cord I/R injury.