Wanru Duan, Dean Chou, Bowen Jiang, Zhenlei Liu, Xinghua Zhao, Zhiyuan Xia, Fengzeng Jian and Zan Chen
The treatment of atlantoaxial dislocation (AAD) and basilar invagination (BI) is challenging, especially in symptomatic patients with a history of previous surgery. Although seldom reported, posterior revision surgery to revise prior constructs can be advantageous over an anterior or combined approach. The authors describe their experience in performing posterior revision surgery using Goel’s technique.
The authors reviewed patients with AAD and BI who had undergone previous posterior surgery at the cranio-cervical junction between January 2016 and September 2017. All of these patients underwent revision surgery from a posterior approach. The Japanese Orthopaedic Association (JOA) score was used to assess clinical symptoms before and after surgery. The distance from the tip of the odontoid to Chamberlain’s line, atlantodental interval (ADI), and clivus-canal angle (CCA) were used for radiographic assessment before and after surgery.
Twelve consecutive patients were reviewed. Prior surgeries were as follows: 4 patients (4/12) with posterior osseous decompression without fusion, 7 (7/12) with reduction and fusion without decompression, and 1 (1/12) with posterior osseous decompression and reduction and fusion. With the use of Goel’s technique for revision in these cases, distraction using facet spacers afforded release of the anterior soft tissue from a posterior approach. The occiput was fixated to C2 using a cantilever technique, and autologous cancellous bone was grafted into the intraarticular joints. In all 12 patients, complete reduction of BI and AAD were achieved without injury to nerves or vessels. All patients had evidence of bony fusion on CT scans within 18 months of follow-up.
Posterior revision surgery using Goel’s technique is an effective and safe revision salvage surgery for symptomatic patients with AAD and BI.
Nagore I. Marín-Ramos, Marta Pérez-Hernández, Anson Tam, Stephen D. Swenson, Hee-Yeon Cho, Thu Zan Thein, Florence M. Hofman and Thomas C. Chen
Glioblastoma (GBM) is the most aggressive type of brain tumor with a high rate of tumor recurrence, and it often develops resistance over time to current standard of care chemotherapy. Its highly invasive nature plays an essential role in tumor progression and recurrence. Glioma stem cells (GSCs) are a subpopulation of glioma cells highly resistant to treatments and are considered responsible for tumor recurrence.
Patient-derived populations of GSCs were analyzed by western blot, MTT, and cytoplasmic calcium labeling to determine the cytotoxicity of NEO100. High-performance liquid chromatography was used to evaluate the levels of NEO100 in the cell culture supernatants. The effects of the compound on GSC motility were studied using Boyden chamber migration, 3D spheroid migration and invasion assays, and an mRNA expression PCR array. A RhoA activation assay, western blot, and immunofluorescence techniques were employed to confirm the signaling pathways involved. Intracranial implantation of GSCs in athymic mice was used to evaluate the effects of NEO100 in vivo on tumor progression and overall survival.
Here, the authors show how NEO100, a highly purified guanosine monophosphate–quality form of perillyl alcohol, is cytotoxic for different subtypes of GSCs, regardless of the mechanisms of DNA repair present. At doses similar to the IC50 (half maximal inhibitory concentration) values, NEO100 induces ER stress and activates apoptotic pathways in all GSC populations tested. At subcytotoxic doses in the micromolar range, NEO100 blocks migration and invasion of GSCs. These results correlate with a decrease in calpain-1 expression and an increase in RhoA activation, leading to enhanced contractility of the GSCs. In addition, NEO100 blocks the activation of the kinases Src, p42/44 MAPK, Akt, and Stat3, all related to cell proliferation and migration. Intranasal administration of NEO100 in mice with GSC-derived intracranial tumors led to a decrease in tumor progression and a 32% increase in overall survival. Immunostaining studies showed that NEO100 induces apoptosis and reduces GSC invasion in vivo.
NEO100 could have significant value targeting GSCs and could be used for GBM therapy as either monotherapy or a coadjuvant therapy during temozolomide rest cycles.