Glioblastoma is a fatal and incurable cancer with the hyper-activated mTOR pathway. HSP60, a major chaperone for maintenance of mitochondrial proteostasis, is highly expressed in glioblastoma patients. To understand the effects of HSP60 on glioblastoma tumorigenesis and progression, we characterized the HSP60-knockdowned glioblastoma cells and revealed that HSP60 silencing markedly suppressed cell proliferation and promoted cell to undergo the epithelial-mesenchymal transition (EMT). Proteomic analysis showed that ribosomal proteins were significantly downregulated whereas EMT-associated proteins were up-regulated in HSP60-knockdowned U87 cells as confirmed by a distinct enrichment pattern in newly synthesized proteins with azido-homoalanine labeling. Biochemical analysis revealed that HSP60 knockdown increased reactive oxygen species (ROS) production that led to AMPK activation, similarly to the complex I inhibitor rotenone-induced AMPK activation. Activated AMPK suppressed mTORC1 mediated S6K and 4EBP1 phosphorylation to decrease protein translation, which slowed down cell growth and proliferation. On the other hand, high levels of ROS in HSP60 knockdowned or rotenone-treated U87 cells contributed to EMT. These results indicate that HSP60 silencing deactivates the mTOR pathway to suppress glioblastoma progression, suggesting that HSP60 is a potential therapeutic target for glioblastoma treatment.

Object Intraspinal hemangioblastomas are relatively uncommon benign tumors. The surgical strategies remain controversial, and the risk factors with regard to clinical outcome are unclear. The purpose of this study was to analyze the clinical characteristics, imaging findings, surgical strategies, and functional outcomes associated with intraspinal hemangioblastomas. Methods A series of 92 patients who underwent 102 operations for resection of 116 intraspinal hemangioblastomas at a single institution during 2007–2011 were consecutively enrolled in this study. Of these, 60 patients (65.2%) had sporadic hemangioblastomas and 32 (34.8%) had von Hippel-Lindau disease. Preoperatively, 13 patients underwent digital subtraction angiography (DSA), 15 patients underwent 3D CT angiography (3D CTA), and none underwent preoperative embolization. Clinical characteristics, imaging findings, and operative records were analyzed. The advantages and disadvantages of DSA and 3D CTA were compared. For identification of risk factors that affect prognosis, logistic analysis was performed. Results The male/female patient ratio was 1.8:1.0 (59 male and 33 female patients). Of the tumors, 41% were intramedullary, 37% were intramedullary-extramedullary, and 22% were primarily extramedullary. Three-dimensional CTA and DSA did not differ significantly in the ability to identify the feeding arteries (p = 1.000) and image qualities (p = 0.367). However, compared with 3D CTA, the effective x-ray dose of spinal DSA was 2.73 times higher and the mean amount of contrast media injected was 1.88 times higher. Spinal DSA was more time consuming (mean 120 minutes) than 3D CTA (scanning time < 1 minute). No complications were observed after 3D CTA; acute paraparesis developed in 1 patient after DSA. Gross-total resection was achieved for 109 tumors (94.0%), and resection was subtotal for 7 tumors. Mean duration of follow-up was 50 months (range 24–78 months). At the most recent follow-up visit, the functional outcome was improved for 38 patients (41.3%), remained stable for 40 (43.5%), and deteriorated for 14 (15.2%). Logistic analysis showed that subtotal resection was a risk factor affecting prognosis (p = 0.003, OR 12.833, 95% CI 2.429–67.806). Conclusions The authors' study suggests that safe and effective treatment of intraspinal hemangioblastomas can be achieved for most patients, even without preoperative embolization. Gross-total resection, when safe to perform, leads to better outcomes. Compared with spinal DSA, 3D CTA is a promising technique because it is noninvasive, takes less time to perform, requires lower x-ray doses and less contrast media, results in fewer complications, and offers high accuracy for delineating the feeding arteries.

Object Extradural en plaque meningiomas are very rare tumors in the spinal canal. Most studies on these lesions have been case reports with literature reviews. In this paper, the authors review their experience in a surgical series of 12 patients with histologically proven, purely extradural en plaque meningiomas and discuss their clinical features, radiological findings, and long-term outcomes. Methods Clinical and imaging data of 12 patients with spinal extradural en plaque meningiomas treated at a single institution were retrospectively analyzed. Results There were 5 male and 7 female patients, with a mean age of 39.9 years. The mean follow-up period was 74.8 months. Nine tumors were located in the cervical spine, 1 in the cervicothoracic spine, and 2 in the thoracic spine. All the tumors were confirmed as extradural en plaque meningiomas with sheetlike growth along the dura mater. Gross-total resection of the tumor with a well-demarcated dissection plane was achieved in 4 cases. Subtotal resection was achieved in 8 cases, 2 of whom underwent postoperative low-dose radiation therapy. The symptoms present before the surgery were improved in all cases at the last follow-up evaluation. The postoperative follow-up MRI showed no recurrence or regrowth in 4 cases with gross-total removal and 7 cases with subtotal removal during the mean follow-up periods of 58.0 months and 71.1 months, respectively. One patient experienced recurrence at 88 months after his initial subtotal removal and improved following a revision operation. Conclusions Spinal extradural en plaque meningiomas are amenable to surgery if complete removal can be achieved. Because of the encirclement of the dura that is characteristic of the tumors, complete resection is usually difficult, subtotal removal for spinal cord decompression is advised, and follow-up imaging is needed. The risk of long-term recurrence/regrowth of the lesions is low, and a good clinical outcome after total or subtotal removal can be expected.

Surgical resection of intramedullary CMs eliminates the risk of subsequent hemorrhagic and may achieve satisfactory outcome when patients are carefully selected. Although conservative management is recommended in patients at high surgical risk, they should be closely monitored because of persistent hemorrhagic risk.