Clinical study of puncture technique in single division of the trigeminal ganglion intumescentia.

OBJECTIVE: We explored the feasibility of single-division puncture in the ophthalmic division, maxillary division, and mandibular division of the trigeminal ganglion intumescentia (TGI) and the feasibility of radiofrequency treatment of trigeminal neuralgia. METHODS: According to the previous anatomical image studies, 3D Slicer software was used to analyze the CT images of the patients. The trigeminal ganglion fossa (TGF) was used as the imaging sign. TGI was identified in the sagittal plane along the fiber. The puncture path starts from the TGI center-foramen ovale line, extending outward to the epidermis as the needle insertion point, and extending inward to the division boundary. For lateral puncture, which is blocked by the mandible, the positions of closed mouth, open mouth, and over-open mouth were used. Multiple targets were generated using straight electrodes and curved electrodes to achieve full coverage of TGI. According to the preoperative design, general anesthesia surgery was performed. Xper CT was used for imaging, and the puncture was guided by Xper Guide. Radiofrequency treatment of TGI was conducted. RESULTS: In total, 45 patients with trigeminal neuralgia underwent 50 single-division TGI punctures. The procedure was smooth and the compliance with the design was good. Continuous radiofrequency (CRF) was performed, the VAS scores were 25 times at 70°C, 19 times at 65°C, two times at 60°C, and two times at 50°C (both in the ophthalmic division). Pulsed radiofrequency (PRF) was conducted two times. Within 24 h after the procedure, the VAS scores were all 0. From 1 to 7 days after the procedure, pain recurrence was found in three cases, of whom two cases received pulsed radiofrequency treatment. Patients were followed up for 1-24 months and there were no recurrence. After continuous radiofrequency at 65-70°C, the moderate tactile loss was observed, and nearly half of the patients had food residues on the surgical side after 6 months. After continuous radiofrequency at 60°C, there was mild tactile loss and no food residue. The tactile sensation was slightly decreased after continuous radiofrequency at 50°C, and the tactile sensation was normal the next day. CONCLUSION: Trigeminal ganglion intumescentia single-division radiofrequency is effective and feasible for the treatment of trigeminal neuralgia.

FoxR2 promotes glioma proliferation by suppression of the p27 pathway.

FoxR2 plays an important role in the development of many human tumors. However, the effects of FoxR2 on tumorigenicity of human glioma remain unclear. In this study, we investigated the roles of FoxR2 in cell proliferation and invasion of glioma. We found that overexpression of FoxR2 promoted the proliferation, migration and invasion of glioma cells. Knockout of FoxR2 induced G1 arrest by decreasing the expression levels of cyclin D1, cyclin E and p-Rb. Mechanistically, upregulation of FoxR2 increased the level and activity of MMP-2 and decreased the expression of p27. Furthermore, overexpression of FoxR2 decreased the nuclear accumulation of p27. Taken together, these results indicate that upregulation of FoxR2 may confer enhanced tumorigenicity in glioma cells.

Smoothened is a poor prognosis factor and a potential therapeutic target in glioma.

Malignant gliomas are associated with a high mortality rate. Thus, there is an urgent need for the development of novel targeted therapeutics. Aberrant Hedgehog signaling has been directly linked to glioma. GDC-0449 is a novel small molecule inhibitor of Hedgehog signaling that blocks the activity of smoothened (Smo). In this study, we evaluated the in vitro and in vivo effects of the smoothened inhibitor GDC-0449 on cell proliferation in human gliomas. We found that high expression of smoothened in glioma is a predictor of short overall survival and poor patient outcome. Our data suggest that GDC-0449 significantly inhibits the proliferation of glioma cells by inducing cell cycle arrest at the G1 phase. Our results demonstrate that GDC-0449 can effectively inhibit the migration and invasion of glioma cells. Furthermore, GDC-0449 treatment significantly suppressed glioma cell xenograft tumorigenesis. Mechanistically, GDC-0449 treatment markedly decreases the expression levels of key Hedgehog pathway component genes (Shh, Patched-1, Patched-2, smoothened, Gli1 and Gli2). These results indicate that GDC-0449 works through targeting the Hedgehog pathway. Taken together, our study suggests that smoothened could be used as a prognostic marker and molecular therapeutic target for glioma.

CRM1/XPO1 is associated with clinical outcome in glioma and represents a therapeutic target by perturbing multiple core pathways.

BACKGROUND: Malignant gliomas are associated with a high mortality rate, and effective treatment options are limited. Thus, the development of novel targeted treatments to battle this deadly disease is imperative. METHODS: In this study, we investigated the in vitro effects of the novel reversible chromosomal region maintenance 1 (CRM1) inhibitor S109 on cell proliferation in human gliomas. S109 was also evaluated in an intracranial glioblastoma xenograft model. RESULTS: We found that high expression of CRM1 in glioma is a predictor of short overall survival and poor patient outcome. Our data demonstrate that S109 significantly inhibits the proliferation of human glioma cells by inducing cell cycle arrest at the G1 phase. Notably, we observed that high-grade glioma cells are more sensitive to S109 treatment compared with low-grade glioma cells. In an intracranial mouse model, S109 significantly prolonged the survival of tumor-bearing animals without causing any obvious toxicity. Mechanistically, S109 treatment simultaneously perturbed the three core pathways (the RTK/AKT/Foxos signaling pathway and the p53 and Rb1 tumor-suppressor pathways) implicated in human glioma cells by promoting the nuclear retention of multiple tumor-suppressor proteins. CONCLUSIONS: Taken together, our study highlights the potential role of CRM1 as an attractive molecular target for the treatment of human glioma and indicates that CRM1 inhibition by S109 might represent a novel treatment approach.