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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Malignant astrocytomas are among the most common brain tumours and few therapeutic options exist. It has recently been recognized that the ligand-activated nuclear receptor PPARγ can regulate cellular proliferation and induce apoptosis in different malignant cells. We report the effect of three structurally different PPARγ agonists inducing apoptosis in human (U87MG and A172) and rat (C6) glioma cells. The PPARγ agonists ciglitazone, LY171 833 and prostaglandin-J2, but not the PPARα agonist WY14643, inhibited proliferation and induced cell death. PPARγ agonist-induced cell death was characterized by DNA fragmentation and nuclear condensation, as well as inhibited by the synthetic receptor-antagonist bisphenol A diglycidyl ether (BADGE). In contrast, primary murine astrocytes were not affected by PPARγ agonist treatment. The apoptotic death in the glioma cell lines treated with PPARγ agonists was correlated with the transient up-regulation of Bax and Bad protein levels. Furthermore, inhibition of Bax expression by specific antisense oligonucleotides protected glioma cells against PPARγ-mediated apoptosis, indicating an essential role of Bax in PPARγ-induced apoptosis. However, PPARγ agonists not only induced apoptosis but also caused redifferentiation as indicated by outgrowth of long processes and expression of the redifferentiation marker N-cadherin in response to PPARγ agonists. Taken together, treatment of glioma cells with PPARγ agonists may hold therapeutic potential for the treatment of gliomas.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1459
    Keywords: Key words Glioblastoma multiforme ; Oligodendroglial differentiation ; Long-term survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The overall prognosis for patients with glioblastoma multiforme is extremely poor. However, a small proportion of patients enjoy prolonged survival. This study investigated retrospectively the extent to which erroneous histopathological classification may contribute to long-term survival of patients initially diagnosed with “glioblastoma multiforme”. We compared two age- and gender-matched patient groups with different postoperative time to tumor progression (TTP), defined as “short-term” for TTP of less than 6 months (n=54) and “long-term” for TTP of more than 12 months (n=52). Histological specimens of the corresponding tumors, all primarily diagnosed as glioblastome multiforme, were reevaluated according to the current World Health Organization (WHO) classification of central nervous system tumors, with the investigators being blinded to clinical outcome. Among the tumors from short-term TTP patients, one tumor (2%) was reclassified as anaplastic oligoastrocytoma (WHO grade III) while the remaining 53 were confirmed as glioblastoma multiforme. In contrast, 13 tumors (25%) from the long-term TTP patients were reclassified, mostly as anaplastic oligodendroglioma (WHO grade III; n=7) or anaplastic oligoastrocytoma (WHO grade III, n=2), respectively. In addition, three were reclassified as anaplastic astrocytoma (WHO grade III), and one was identified as anaplastic pilocytic astrocytoma (WHO grade III). Our data indicate that a sizable proportion of glioblastoma patients with long-term survival actually carry malignant gliomas with oligodendroglial features. The correct histopathological recognition of these tumors has not only progrostic but also therapeutic implications, since oligodendroglial tumors are more likely to respond favorably to chemotherapy.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neurology 245 (1998), S. 731-733 
    ISSN: 1432-1459
    Keywords: Key words Activated protein C ; Activated protein C resistance ; Dural arteriovenous fistula ; Venous ; thrombosis ; Thrombophilia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Resistance to activated protein C (APCR), shown to be the most common genetic risk factor for venous thrombosis, is mostly caused by a mutation in the factor V (FV) gene leading to FV Leiden. As dural arteriovenous fistulas (DAVFs) are associated with cerebral venous thrombosis, we looked for the FV Leiden mutation in seven patients with such fistulas. The APCR ratio was determined according to standard procedures. For APCR ratios considered pathological (less than 2.0), mutation analysis was done by a reverse hybridization assay. Three of the seven patients with DAVFs showed pathological APCR ratios and heterozygosity for FV Leiden mutation. Thus, it is hypothesized that FV Leiden might be involved in the pathogenesis of DAVFs.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1459
    Keywords: Key words Activated protein C resistance ; Factor V Leiden ; Dural arteriovenous fistula ; Venous thrombosis ; Thrombophilia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Resistance to activated protein C (APCR) is the most common genetic risk factor for venous thrombosis and is generally caused by a mutation in the factor V (FV) gene leading to FV Leiden. The recent finding of FV Leiden in three of seven patients with dural arteriovenous fistulas (DAVFs) prompted us to evaluate systematically the role of APCR due to FV Leiden in the pathogenesis of DAVFs in 22 patients and age- and sex-matched controls. We found a significantly higher frequency of APCR and FV Leiden in the patient group than among controls (5/22 vs. 0/22, P=0.048, Fisher's exact test). We conclude that APCR due to FV Leiden is of pathogenetic significance in a subgroup of DAVFs.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-7373
    Keywords: glioblastoma multiforme ; long-term survival ; TP53 ; PTEN ; CDKN2A ; tumor suppressor gene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Despite multimodal therapy, glioblastoma multiforme (GBM) is associated with a poor prognosis with a median survival of less than 1 year. However, a small number of patients with GBM shows survival times of several years. Although clinical features like age and performance status at diagnosis are well known prognostic parameters, molecular markers for prognosis of overall survival are still lacking. Therefore, we compared 2 age- and gender-matched groups of GBM patients with different post-operative time to tumor progression (TTP), defined as 'short-term' for TTP of less than 6 months (n=21), and 'long-term' for TTP of more than 24 months (n=21) for genetic alterations of the PTEN, CDKN2A and TP53 genes as well as overexpression of the EGFR, p53 and Mdm2 proteins. For the GBMs with 'short-term' TTP vs. 'long-term' TTP, the studies revealed PTEN mutations in 4/21 vs. 2/21, TP53 mutations in 5/21 vs. 8/21, homozygous deletion of the CDKN2A gene in 5/21 vs. 6/21, overexpression of EGFR in 7/20 vs. 10/20, accumulation of p53 protein in 9/20 vs. 7/20 and of Mdm2 protein in 0/20 vs. 1/20 cases studied. Taken together, our data indicate that mutations of the PTEN and TP53 tumor suppressor genes, homozygous deletion of the CDKN2A gene as well as overexpression of the EGFR, p53 and Mdm2 proteins lack prognostic significance for overall survival time in patients with GBMs.
    Type of Medium: Electronic Resource
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