International journal of molecular medicine
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The NF2 tumor suppressor gene, located in chromosome 22q12, is involved in the development of sporadic meningiomas of the nervous system. In order to evaluate the role of the NF2 gene in sporadic meningiomas, we analyzed the entire coding regions of the NF2 gene in a group of 42 sporadic meningiomas: 17 meningothelial, 11 transitional, 11 fibrous, one secretory, one atypical, and one malignant subtype, using denaturing high-performance liquid chromatography (DHPLC) and sequence analysis. Twenty-one mutations were identified in 20 patients with an overall mutation detection rate of 47.6%. ⋯ All mutations were noted in the first 12 exons, the region of homology with the ezrin-moesin-radixin protein. Furthermore, an association between NF2 mutations and histologic subtypes were observed; NF2 mutations were more frequent in fibrous meningiomas (8/11, 73%) and transitional meningiomas (6/11, 55%), than in meningothelial variant (5/17, 29%). These results provide evidence that mutations in the NF2 gene play an important role in the development of sporadic meningiomas as well as indicating a different tumorigenesis of these meningioma variants.
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Cyclooxygenase (COX)-2 is upregulated in a variety of human cancers, including in hepatocellular carcinoma (HCC), whereas it is undetectable in most normal tissue. Evidence suggests that COX-2 is likely to be involved in hepatocarcinogenesis and, thus, COX-2 may be involved in an early process in carcinogenesis, dedifferentiation. To address this possibility, we investigated the effect of COX-2 inhibitors on TNF-related apoptosis, inducing ligand (TRAIL) sensitivity and its molecular mechanisms, with special attention to anti-apoptotic proteins. ⋯ Survivin expression was also down-regulated in the presence of NS398 in HLE cells. Finally, NS398 also decreased phospho-AKT in SK-Hep1 cells. These results demonstrate that COX-2 inhibitors can induce apoptosis and augment TRAIL sensitivity by up-regulation of TRAIL receptors and down-regulation of both survivin and AKT signaling.