MicroRNAs (miRNAs) are effective post-transcriptional regulators of gene expression and are important in many biological processes. Although the oncogenic and tumor suppressive functions of several miRNAs have been characterized, the role of miRNAs in mediating tumor invasion and migration remains largely unexplored. Recently, miR-10b was identified as an miRNA highly expressed in metastatic breast cancer, promoting cell migration and invasion. Here, we performed real-time reverse transcriptase polymerase chain reaction (RT-PCR) assays on 43 glioma samples (17 glioblastoma, 6 anaplastic astrocytoma, 10 low-grade astrocytoma, 6 oligodendroglioma and 4 ependymoma) and 6 glioma cell lines. We found that miR-10b expression was upregulated in all glioma samples compared to non-neoplastic brain tissues. The expression levels of miR-10b were associated with higher grade glioma. In addition, mRNA expressions of RhoC and urokinasetype plasminogen activator receptor (uPAR), which were thought to be regulated by miR-10b via HOXD10, were statistically significantly correlated with the expression of miR-10b (p < 0.001, p 5 0.001, respectively). Also, protein expression levels of RhoC and uPAR were associated with expression levels of miR-10b (p 5 0.009, p 5 0.014, respectively). Finally, multifocal lesions on enhanced MRI of 7 malignant gliomas were associated with higher expression levels of miR-10b (p 5 0.02). Our data indicated that miR-10b might play some role in the invasion of glioma cells. ' 2009 UICC
Cerebral hyperperfusion syndrome after CEA and CAS occurs with delayed classic and acute presentations, respectively. Although strict control of postoperative blood pressure prevents intracranial hemorrhage in patients with CHS after CEA, there appears to be no relationship between blood pressure control and intracranial hemorrhage in those with CHS after CAS. Finally, the prognosis of CHS in patients with associated intracerebral hemorrhage is poor.
Background and Purpose-Hyperperfusion syndrome is a rare but potentially devastating complication after carotid endarterectomy (CEA). The aim of this study was to investigate whether preoperative measurement of cerebral vasoreactivity (CVR) and intraoperative measurement of internal carotid artery (ICA) flow could identify patients at risk for hyperperfusion after CEA. Methods-For 26 patients with unilateral ICA stenosis Ն70%, cerebral blood flow (CBF) and CVR were investigated before and 1 month after CEA, with resting and acetazolamide-challenge single-photon emission CT. CBF on the first postoperative day was also measured. ICA flow was measured before and after reconstruction by electromagnetic flowmeter during surgery. Results-Ipsilateral CBF on the first postoperative day significantly increased relatively (56.6Ϯ53.2%) as well as absolutely (37.9Ϯ8.8 to 57.7Ϯ18.0 mL/100 g per minute) in the reduced CVR group (CVR Ͻ12%) but not in the normal CVR group (CVR Ն12%) (10.3Ϯ15.5% and 40.6Ϯ7.9 to 43.9Ϯ5.7 mL/100 g per minute, respectively). One month later, this difference almost disappeared. Two patients showed ipsilateral CBF increase of Ն100%. A significant association of intracerebral steal with hyperperfusion (CBF increase Ն100%) on the first postoperative day was also observed. ICA flow increase after reconstruction significantly correlated with CBF increase on the first postoperative day in the reduced CVR group but not in the normal CVR group. The threshold of ICA flow increase for hyperperfusion was estimated to be 330 mL/min in the reduced CVR group. Conclusions-Single-photon emission CT with acetazolamide challenge and ICA flow measurement during surgery could identify patients at risk for hyperperfusion after CEA, in whom careful monitoring and control of blood pressure should be initiated even intraoperatively. (Stroke. 2001;32:1567-1573.)
The diagnosis of primary central nervous system lymphoma (PCNSL) by radiographical examination is often difficult because of its similarity to other brain tumors. To test whether interleukin-10 (IL-10) and IL-6 can be used to distinguish PCNSL from other brain tumors that are radiographically similar, cerebrospinal fluid (CSF) levels of IL-10 and IL-6 were measured in 66 patients with intracranial tumors (PCNSLs: 26 cases; other brain tumors: 40 cases). In the patients with PCNSLs, the median CSF levels of IL-10 and IL-6 were 27 pg/mL and 5.4 pg/mL, respectively. The CSF IL-10 and IL-6 levels were significantly higher in PCNSLs than in the other brain tumors. To validate the diagnostic value of CSF IL-10 in PCNSL, we prospectively examined 24 patients with brain lesions that were suspected to be PCNSL. We observed that the CSF IL-10 levels were significantly higher in PCNSLs than in other brain tumors. At an IL-10 cutoff level of 9.5 pg/mL, the sensitivity and specificity were 71.0% and 100%, respectively. After therapy, the CSF IL-10 levels were decreased in all patients and were increased at relapse in most of these patients. Immunohistochemically, all PCNSLs, except for 1 unclassified PCNSL, expressed both IL-10 and IL-10 receptor-A. In the patients with high CSF IL-10, IL-10 expression levels in tumor were relatively higher, compared with low CSF IL-10; however, there was no significant difference between these groups. In addition, elevated CSF level of IL-10 was significantly associated with having a shorter progression-free survival (hazard ratio, 3.37; 95% confidence interval, 0.985-11.528; log-rank, P= .038). These results indicate that the CSF level of IL-10 may be a useful diagnostic and prognostic biomarker in patients with PCNSLs.
Two cases of germ cell tumors (GCTs) of the basal ganglia are presented and 40 previously reported cases are reviewed. The incidence of GCTs of the basal ganglia and thalamus was estimated as less than 14% of all intracranial GCTs. All patients except for two (95%) were male, aged 7-19 years. The clinical course was usually slow. The major symptoms were hemiparesis, mental deterioration such as dementia or character change, precocious puberty, diabetes insipidus, oculomotor palsy, speech disturbance, and hemianopsia. Signs of intracranial hypertension did not occur until the late stages of the disease. The plain CT finding was characterized by an irregularly defined, slightly high-density area frequently accompanied by central low-density areas without significant mass effect. The tumors showed mild to moderate and nonhomogeneous contrast enhancement. An ipsilateral cerebral hemiatrophy was often found. MR images demonstrated the corresponding findings. GCTs of the basal ganglia had a high possibility of containing components other than germinoma such as choriocarcinoma, endodermal sinus tumor, and embryonal carcinoma. Thus, tumor markers in the serum, CSF, or cyst fluid were frequently positive. With recent refinement of microsurgical techniques as well as immunohistochemical study and measurements of tumor markers of serum, CSF, and cyst fluid, major resections of tumor, accurate pretreatment histologic diagnosis, and early determination of the specific types of this tumor appear to be readily possible. This is essential for effective treatment of patients not only with radiosensitive germinoma, but also those with radioinsensitive nongerminoma variants and a combination of them located in this region.
Excellent results from multiple burr-hole operations for adult moyamoya disease are reported in this study. Ten patients had between one and four burr holes (mean 2.1) drilled in each hemisphere. In four patients new burr holes were added on the opposite side after depression of cerebral blood flow (CBF) was detected by follow-up single-photon emission computerized tomography imaging of the brain with N-isopropyl-p-[123I]iodoamphetamine. The postoperative follow-up period ranged from 6 to 62 months (mean 34.7 months). Beginning at 6 months postsurgery, angiograms disclosed rich neovascularization at 41 of 43 burr holes, first from the middle meningeal artery, then from the superficial temporal artery. Neovascularization did not occur at two burr holes at which there was subdural effusion and local cerebral atrophy, respectively. Progression of stenosis of the major vessels was seen in six patients. Moyamoya vessels were decreased at six sites in four patients. The CBF study revealed that the reactivity to acetazolamide improved in all six patients tested. Transient ischemic attacks disappeared in all six patients presenting with this symptom, and preoperative symptoms improved in both of the patients who presented with cerebral infarction and in both patients with intraventricular hemorrhage. There was no mortality or morbidity, and no new neurological deficits or rebleeding developed during the follow-up period. The authors strongly recommend the multiple burr- hole operation as the surgical treatment of choice for adult moyamoya disease because of its safety and effectiveness.
Metabolomics has recently undergone rapid development; however, metabolomic analysis in cerebrospinal fluid (CSF) is not a common practice. We analyzed the metabolite profiles of preoperative CSF samples from 32 patients with histologically confirmed glioma using gas chromatography/mass spectrometry (GC/MS). We assessed how alterations in the metabolite levels were related to the World Health Organization (WHO) tumor grades, tumor location, gadolinium enhancement on magnetic resonance imaging (MRI), and the isocitrate dehydrogenase (IDH) mutation status. Sixty-one metabolites were identified in the CSF from glioma patients using targeted, quantitative and non-targeted, semi-quantitative analysis. The citric and isocitric acid levels were significantly higher in the glioblastoma (GBM) samples than in the grades I–II and grade III glioma samples. In addition, the lactic and 2-aminopimelic acid levels were relatively higher in the GBM samples than in the grades I–II glioma samples. The CSF levels of the citric, isocitric, and lactic acids were significantly higher in grade I–III gliomas with mutant IDH than in those with wild-type IDH. The tumor location and enhancement obtained using MRI did not significantly affect the metabolite profiles. Higher CSF levels of lactic acid were statistically associated with a poorer prognosis in grades III–IV malignant gliomas. Our study suggests that the metabolomic analysis of CSF from glioma patients may be useful for predicting the glioma grade, metabolic state, and prognosis of gliomas.Electronic supplementary materialThe online version of this article (doi:10.1007/s11060-013-1090-x) contains supplementary material, which is available to authorized users.
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