Effects of viscous indigestible polysaccharides on the pancreas exocrine function were investigated in growing rats. Rats were fed a nonfiber diet or a diet containing approximately 5% of one of the following fibers: apple pectin, lambda-carrageenan, locust bean gum, gum xanthan, guar gum or sodium (Na) alginate. Pancreatic-bile secretion was found to be elevated in rats fed for 2 wk the highly viscous polysaccharides, sodium alginate, locust bean gum, gum xanthan and guar gum. The polysaccharides may have interfered with the digestion and absorption of nutrients, resulting in a decreased digestibility and an enlargement of digestive organs. When alginic acid and calcium alginate, insoluble polysaccharides that did not contribute to viscosity, were given to rats, they had no effect on pancreatic and biliary secretion compared with sodium alginate. The results demonstrate that consumption of viscous indigestible polysaccharides leads to changes in the exocrine pancreatic-biliary function and may depress the process of digestion and absorption. Rats may compensate for the inefficiency of digestion and absorption with a hyperplasia/hypertrophy of digestive organs and an increased secretion of digestive juice.

Malignant gliomas are characterized by active invasiveness, necrosis, and vascular proliferation. These pathological features have been speculated to be caused by tissue hypoxia. Hypoxia-inducible factor-1 (HIF-1), which is controlled by rapid stabilization of the HIF-1• subunit, is a pivotal transcriptional factor in the cellular response to hypoxia. Although many studies have described the relationship between tumor angiogenesis and hypoxic environment, the roles of HIF-1 in cell invasion have been barely elucidated in malignant gliomas. We investigated the role of HIF-1• in the motile and invasive activities of human glioma cells under hypoxia. Four malignant glioma cell lines, U87MG, U251MG, U373MG, and LN18, were cultured under 21 and 1% oxygen concentration. Expression of HIF-1• under hypoxia was observed to be much higher than that under normoxia in all cell lines. Introducing HIF-1•-targeted small interfering RNA (HIF-1• siRNA) into the glioma cell lines resulted in downregulation of HIF-1• expression, and significantly suppressed glioma cell migration in vitro. Furthermore, invasiveness was significantly reduced in the cells transfected with HIF-1• siRNA compared with those transfected with the control siRNA. Co-culture of glioma spheroids and rat brain slices showed that HIF-1• siRNAtransfected glioma cells failed to invade the surrounding normal brain tissue in an organotypic brain slice model. These effects of HIF-1• siRNA were more conspicuous under hypoxia than under normoxia. In addition, under hypoxic conditions, the level of matrix metalloproteinase (MMP)-2 mRNA was upregulated, and that of tissue inhibitor of metalloproteinase (TIMP)-2 was downregulated in all glioma cell lines. Treatment with HIF-1• siRNA resulted in downregulation of MMP-2 mRNA and upregulation of TIMP-2 mRNA. Furthermore, the enzyme activities of MMP-2 and MMP-9, both of which were activated by hypoxia, decreased with the introduction of HIF-1• siRNA. These findings suggest that overexpression of HIF-1• induced by hypoxic stress is an essential event in the activation of glioma cell motility through alteration of invasion-related molecules. Targeting the HIF-1• molecule may be a novel therapeutic strategy for malignant gliomas.

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.

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.

Glioma-initiating cells (GIC) have stem-like cell properties thought to be sufficient for recurrence, progression, and drug resistance in glioblastomas. In the present study, we defined miRNA (miR)-340 as a differentially expressed miRNA in human GICs that inhibit GIC-mediated tumorigenesis. Furthermore, we defined tissue plasminogen activator (PLAT) as a critical direct target of miR340 for inhibition. Among miRNAs screened, we found that miR340 expression was decreased in all human GICs and in human glioblastoma tissues, compared with human neural stem cells and normal brain tissues. miR340 overexpression in GICs suppressed their proliferative, invasive, and migratory properties in vitro, triggering cell senescence in vitro and inhibiting GIC-induced tumorigenesis in mouse brains. shRNA-mediated silencing of PLAT in GICs phenocopied the effects of miR340 overexpression in vitro and in vivo, suggesting a potential role for tissue factor in stem-like cell function. Taken together, our results identified miR340 as a tumor suppressor that functions in GIC to enforce PLAT blockade and ablate their stem-like functions.