DT imaging-based fiber tracking is a reliable and accurate method for mapping the course of subcortical PTs. Fiber tracking and intraoperative MEPs were useful for preserving motor function in patients with gliomas near the PT.
Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor and a subpopulation of glioma stem-like cells (GSCs) is likely responsible for the invariable recurrence following maximum resection and chemoradiotherapy. As most GSCs that are located in the perivascular and perinecrotic niches should be removed during tumor resection, it is very important to know where surviving GSCs are localized. Here, we investigated the existence and functions of GSCs in the tumor periphery, which is considered to constitute the invasion niche for GSCs in GBM, by analyzing expression of stem cell markers and stem cell-related molecules and measuring particular activities of cultured GSCs. In addition, the relationship between GSCs expressing particular stem cell markers and pathological features on MRI and prognosis in GBM patients was analyzed. We showed that GSCs that express high levels of CD44 are present in the tumor periphery. We also found that vascular endothelial growth factor (VEGF) is characteristically expressed at a high level in the tumor periphery. Cultured GSCs obtained from the tumor periphery were highly invasive and have enhanced migration phenotype, both of which were markedly inhibited by CD44 knockdown. Higher expression of CD44 in the tumor periphery than in the core was correlated with a highly invasive feature on MRI and was associated with early tumor progression and worse survival, whereas lower expression of CD44 in the tumor periphery corresponded to low invasion and was associated with longer survival. The low invasion type on MRI tended to show high levels of VEGF expression in the tumor periphery, thus presenting the tumor with high proliferative activity. These results imply the significance of GSCs with high levels of CD44 expression in the tumor periphery compared to the core, not only in tumor invasion but also rapid tumor progression and short survival in patients with GBM.
OBJECTIVE-c-Cbl plays an important role in whole-body fuel homeostasis by regulating insulin action. In the present study, we examined the role of Cbl-b, another member of the Cbl family, in insulin action. RESEARCH DESIGN AND METHODS-C57BL/6(Cbl-b ϩ/ϩ ) or Cbl-b-deficient (Cbl-b Ϫ/Ϫ ) mice were subjected to insulin and glucose tolerance tests and a hyperinsulinemic-euglycemic clamp test. Infiltration of macrophages into white adipose tissue (WAT) was assessed by immunohistochemistry and flow cytometry. We examined macrophage activation using co-cultures of 3T3-L1 adipocytes and peritoneal macrophages. RESULTS-ElderlyCbl-b Ϫ/Ϫ mice developed glucose intolerance and peripheral insulin resistance; serum insulin concentrations after a glucose challenge were always higher in elderly Cbl-b Ϫ/Ϫ mice than age-matched Cbl-b ϩ/ϩ mice. Deficiency of the Cbl-b gene significantly decreased the uptake of 2-deoxyglucose into WAT and glucose infusion rate, whereas fatty liver was apparent in elderly Cbl-b Ϫ/Ϫ mice. Cbl-b deficiency was associated with infiltration of macrophages into the WAT and expression of cytokines, such as tumor necrosis factor-␣, interleukin-6, and monocyte chemoattractant protein (MCP)-1. Co-culture of Cbl-b Ϫ/Ϫ macrophages with 3T3-L1 adipocytes induced leptin expression and dephosphorylation of insulin receptor substrate 1, leading to impaired glucose uptake in adipocytes. Furthermore, Vav1, a key factor in macrophage activation, was highly phosphorylated in peritoneal Cbl-b Ϫ/Ϫ macrophages compared with Cbl-b ϩ/ϩ macrophages. Treatment with a neutralizing anti-MCP-1 antibody improved peripheral insulin resistance and macrophage infiltration into WAT in elderly Cbl-b Ϫ/Ϫ mice. O besity is a major cause of insulin resistance (1) and is considered a chronic low-grade inflammatory disease (2). Substantial evidence has accumulated in recent years that chronic infiltration and activation of macrophages in white adipose tissue (WAT) underlie the obesity-related component of these insulin-resistant states (3-5). Infiltrating macrophages secrete proinflammatory cytokines and stimulate the secretion of adipokines from adipocytes (4,5). Tumor necrosis factor (TNF)-␣ and interleukin (IL)-6 are key factors that induce insulin resistance (6,7). Leptin and adiponectin are also suggested to act as hormones that regulate insulin resistance; hyperleptinemia in obese subjects is associated with insulin resistance in tissues such as liver, WAT, and skeletal muscle (8), whereas adiponectin increases insulin sensitivity of these tissues (9). However, the molecular mechanism of macrophage activation in WAT is still unknown. CONCLUSIONS-Cbl-b is a unique ubiquitin ligase that is associated with maturation and activation of macrophages and T-cells (10,11). Expression of Cbl-b is upregulated by macrophage/monocyte differentiation of HL60 and U937 cell lines (10). Cbl-b influences CD28-dependent T-cell activation by selectively restraining T-cell receptor-mediated Vav1 activation (12)(13)(14). A recent study reported that the ...
Image-guided neurosurgery using navigation systems is an essential tool to increase accuracy in brain tumor surgery. However, brain shift during surgery has remained problematic. The present study evaluated the utility of a new ultrasound (US)-linked navigation system for brain tumor surgery in 64 patients with intracranial tumors. The navigation system consisted of a StealthStation TM navigation system, a SonoNav TM system, and a standard US scanner. This system determines the orientation of the US images and reformats the images from preoperative computed tomography (CT) or magnetic resonance (MR) imaging to match the US images. The system was used intraoperatively to measure brain shift several times, using the results to guide tumor resection. US-linked navigation provided information regarding brain shift, and extent of tumor resection during surgery. Evaluation of brain shift was easily achieved in all patients, without using intraoperative CT or MR imaging. Accurate information regarding the true anatomical configuration of the patient could be obtained in all phases of the operation. Magnitude of brain shift increased progressively from pre-to post-resection and depended on the type of cranial structure. Integration of the US scanner with the navigation system allowed comparisons between the intraoperative US and preoperative images, thus improving interpretation of US images. The system also improved the rate of tumor resection by facilitating the detection of remnant tumor tissue. This US-linked navigation system provides information on brain shift, and improves the accuracy and utility of image-guided surgery.
Autophagy is a conserved system that adapts to nutrient starvation, after which proteins and organelles are degraded to recycle amino acids in response to starvation. Recently, the ER was added to the list of targets of autophagic degradation. Autophagic degradation pathways of bulk ER and the specific proteins sorted through the ER are considered key mechanisms in maintaining ER homeostasis. Four ER-resident proteins (FAM134B, CCPG1, SEC62, and RTN3) have been identified as ER-resident cargo receptors, which contain LC3-interacting regions. In this study, we identified an N-terminal–truncated isoform of FAM134B (FAM134B-2) that contributes to starvation-induced ER-related autophagy. Hepatic FAM134B-2 but not full-length FAM134B (FAM134B-1) is expressed in a fed state. Starvation drastically induces FAM134B-2 but no other ER-resident cargo receptors through transcriptional activation by C/EBPβ. C/EBPβ overexpression increases FAM134B-2 recruitment into autophagosomes and lysosomal degradation. FAM134B-2 regulates lysosomal degradation of ER-retained secretory proteins such as ApoCIII. This study demonstrates that the C/EBPβ-FAM134B-2 axis regulates starvation-induced selective ER-phagy.
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