Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synemin, a very unique type VI intermediate filament (IF) protein, exhibits alternative splice variants termed alpha and beta. Unlike other IF proteins, synemin binds to actin-associated proteins, including alpha-actinin, vinculin, and alpha-dystrobrevin. Our previous work has demonstrated the presence of synemin in differentiating astrocytes. In this study, we have examined the presence of synemin in human astrocytes under pathological conditions, using rabbit antibodies raised against the C-terminal domain of human synemin produced in bacteria. Western blotting shows that astrocytic tumors contain greater amounts of alpha-synemin than do normal brain tissues. These tumors also contain beta-synemin, which is not detectable in normal brain. Immunohistochemistry demonstrates that, while synemin is present in normal adult brain only in vascular smooth muscle cells, it is newly synthesized by reactive and neoplastic astrocytes. Alpha- and beta-Synemins have also been detected by Western blotting and polymerase chain reaction in several human glioblastoma cell lines. In these cell lines, surprisingly, synemin is associated with ruffled membranes in addition to being distributed along the IF network. In ruffled membranes, synemin was found to co-localize with alpha-actinin. This unusual cellular localization for an IF protein is maintained after nocodazole-induced perinuclear coiling of the vimentin IF network. In addition, immunoprecipitation experiments demonstrate that synemin forms a complex with alpha-actinin in glioblastoma cells. Taken together with synemin localization within ruffled membranes, this finding suggests that synemin plays a role in motility of glioblastoma cells.
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PMID:Intermediate filament protein synemin is present in human reactive and malignant astrocytes and associates with ruffled membranes in astrocytoma cells. 1565 40

The search of proliferation markers in astrocytic tumors that may serve as targets for therapeutic interventions, is in full progress. Membrane-bound signal transducers for growth factors are amongst the substances of interest. Gangliosides are lipid-sugar compounds localized on the cell membrane that are thought to modify pertinent signals and, therefore, may influence a variety of functions in normal and pathologic conditions including those that act upon tumor growth. Intracranial supratentorial astrocytic gliomas of the adult represent a tumor group, that may be divided into three grades of malignancy, the most anaplastic member being the glioblastoma. A stepwise anaplasia is assumed and accompanied by genetic events that are partly specific for these grades. In earlier investigations, it had been shown that there is a tendency towards formation of more simple members of the ganglioside family with ongoing malignancy of those tumors. Yet, the results were only partly congruent and the correlation to tumor grades rather loose. We, therefore, investigated the occurrence of triaose gangliosides within these tumors in situ by immunohistochemistry. In this paper, we corroborate our earlier observation that triaose gangliosides preferentially occur within the cytoplasm of large protoplasmic and gemistocytic astrocytes. The potency of the expression of GD2 is calculated and plotted against the expression of two markers of intermediate glial filaments, namely GFAP (glial fibrillary acid protein) and vimentine. A high interdependence of the three compounds could be demonstrated by correlation analysis. Thus, the conclusion must be drawn that the correlation of ganglioside patterns to the proliferation of astrocytic tumors is as poor as that of GFAP or vimentin expression, respectively.
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PMID:Ganglioside (GD2) expression and intermediary filaments in astrocytic tumors. 1569 79

A 67-year-old male presented with a clear cell ependymoma with symptoms of ataxic gait and dizziness. Magnetic resonance imaging showed a ring enhanced and circumscribed mass lesion with some cysts in the left cerebellar hemisphere, and the vertebral artery angiogram showed the vascurality of the tumor fed by both the left posterior inferior cerebellar artery and the left superior cerebellar artery mainly. They demonstrated suspicious finding of metastatic tumor, glioblastoma, or cystic meningioma. Surgery via the left suboccipital approach revealed a whitish and solid tumor, which was demarcated from the cerebellar parenchyma and had no continuity with the 4th ventricle. Total resection of the tumor was successfully performed. The hematoxilyn-eosin staining of the surgical specimen was similar to hemangioblastoma or oligodendroglioma, however, immunohistochemical findings for glial fibrillary acidic protein, vimentin, epithelial membrane antigen, and factor VIII were compatible with clear cell ependymoma. The patient's postoperative course was uneventful, and his symptoms improved. Clear cell ependymoma is known as a variant of ependymoma, which is usually located at the foramen of Monro. We think that the immunohistochemical study is highly helpful for the diagnosis of the cerebellar tumor with atypical presentation such as our case.
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PMID:[Immunohistochemical study is helpful for the diagnosis of cerebellar clear cell ependymoma with atypical radiological findings--case report]. 1627 26

Glioblastoma multiforme is recognized rarely in the cerebellum. We describe a peculiar case with lipid accumulation in giant tumor cells, possibly the second example so far reported in this unusual location. A 46-year-old man with a 5-month history of headache, vomiting, dizziness and instability of gait, was found to have on magnetic resonance imaging an expanding mass situated deep in the left cerebellar hemisphere. The lesion was hypointense in T 1- and hyperintense in T2-weighted images, had poorly defined borders, peripheral edema and annular foci of contrast enhancement. Eight months after subtotal removal and radiotherapy, control MRI showed tumor recurrence with aggressive features. The patient was alive 15 months after operation but follow-up was eventually lost. Histologically, the tumor showed marked pleomorphism, with many giant cells characterized by finely vacuolated cytoplasm strongly suggestive of lipid accumulation. There were few, sometimes atypical mitotic figures and foci of endothelial proliferation. The tumor cells were strongly positive for GFAP, vimentin and S100 protein, all of which stressed the foamy appearance of the giant cells. About 15% of nuclei were positive for Ki-67. We considered the case to be a so-called lipidized glioblastoma, first recognized as a subtype by Kepes and Rubinstein [1981]. Differential diagnosis with anaplastic pleomorphic xanthoastrocytoma is discussed.
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PMID:Lipidized giant-cell glioblastoma of cerebellum. 1632 Aug 20

We recently found that formylpeptide receptor (FPR), a G-protein-coupled receptor that mediates chemotaxis of phagocytic leukocytes induced by bacterial peptide N-formyl-methionyl-leucyl-phenylalanine, is expressed by malignant human glioma cells and promotes tumor growth and angiogenesis. In this study, we examined the effect of Nordy, a novel chiral lipoxygenase inhibitor which was synthesized based on the structure of a natural nordihydroguaiaretic acid, on the expression of FPR by human glioblastoma cells. We found that FPR was expressed at the protein level by highly malignant human glioma cell lines U87 and BT325, and a rat glioma cell line C6. The expression level of FPR was correlated with the degree of the malignancy of tumor cells. The poorly differentiated glioma cell line U87 expressed the highest level of FPR. In U87 glioma cells, the expression of FPR was attenuated at the protein level by Nordy treatment for 48 (P<0.05). Nordy did not affect FPR mRNA expression in U87 cells. In addition, Nordy treatment seemed to promote glioma cell differentiation, as evidenced by their reduced expression of vimentin and increased expression of GFAP. Our results suggest that Nordy was capable of reducing the level of malignancy of glioma cells.
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PMID:Nordy, a synthetic lipoxygenase inhibitor, inhibits the expression of formylpeptide receptor and induces differentiation of malignant glioma cells. 1651 55

The notion that gliomas could originate from mutated glial precursor cells highlights the possibility of modulating the proliferative and migratory behaviour of glioma cells by acting on the molecular mechanisms operative during the development of the Central Nervous System (CNS), but absent in the normal adult brain. We show that the GL15 glioblastoma derived human cell line displays a high expression of nestin which, combined with the previously demonstrated high expression of vimentin, constitutes a characteristic of astrocyte restricted precursors. We also show that, in analogy with some leukaemia cells, GL15 cells display the constitutively phosphorylated form of Janus kinase 2 (JAK2), a tyrosine kinase expressed during CNS development but undetectable in the normal adult brain. The constitutive activation of JAK2 does not result from chromosomal aberrations involving the JAK2 gene, but most probably from abnormally activated transduction systems operative in glioblastoma cells. We then investigated the effects of tyrphostin AG490, an inhibitor of JAK2 autophosphorylation, on GL15 cell growth. In the absence of exogenous growth factors and cytokines, 10 microM tyrphostin AG490 induces an S phase arrest, combined with a partial impairment of the G2 phase of the cell cycle. The abnormally activated JAK2 could then potentially represent a target for a selective pharmacological approach in glioblastoma cells in which a combination of glial precursor characteristics and genetic alterations occurs.
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PMID:Constitutive phosphorylation of Janus kinase 2 in the GL15 glioblastoma derived human cell line. 1714 73

Perivascular epithelioid cell tumor (PEComa) is rare entity and has been described only recently. By immunohistochemistry and genetics it belongs to the family of tumours which comprises angiomyolipoma, clear cell "sugar" tumor of lung, lymphangioleiomyomatosis and clear cell myomelanotic tumor of ligamentum falciforme/teres hepatis. We describe an unusual case of hepatic PEComa arising in a 55-year-old woman with previous history of glioblastoma. Histologically the tumor grew in expansive way, and was composed of clear and eosinophilic epithelioid cels, without vascular or lipomatous component characteristic of angiomyolipoma. There was mild nuclear pleomorphism, sporadic mitotic activity and haemorrhage without necrosis. On immunohistochemistry, the tumor was HMB-45+50, Melan-A and smooth muscle actin positive. Tyrosinase, S-100 protein, cytokeratin coctail, EMA, vimentin, muscle specific actin, CD10, TTF-1, hepatocyte, desmin and cyclin D1 were negative. Sporadic nuclear p53 positivity was seen. The main differential diagnosis of hepatic PEComa includes clear cell variant of liver cell adenoma and hepatocellular carcinoma, metastases of various clear cell carcinomas and metastasis of malignant melanoma. In respect of uncertain biologic potential of PEComa, long term follow up is indicated.
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PMID:[Perivascular epithelioid cell tumor (PEComa) of the liver: a case report and review of the literature]. 1737 Apr 72

Although rodent glioblastoma (GBM) models have been used for over 30 years, the extent to which they recapitulate the characteristics encountered in human GBMs remains controversial. We studied the histopathological features of dog GBM and human xenograft GBM models in immune-deficient mice (U251 and U87 GBM in nude Balb/c), and syngeneic GBMs in immune-competent rodents (GL26 cells in C57BL/6 mice, CNS-1 cells in Lewis rats). All GBMs studied exhibited neovascularization, pleomorphism, vimentin immunoreactivity, and infiltration of T-cells and macrophages. All the tumors showed necrosis and hemorrhages, except the U87 human xenograft, in which the most salient feature was its profuse neovascularization. The tumors differed in the expression of astrocytic intermediate filaments: human and dog GBMs, as well as U251 xenografts expressed glial fibrillary acidic protein (GFAP) and vimentin, while the U87 xenograft and the syngeneic rodent GBMs were GFAP(-) and vimentin(+). Also, only dog GBMs exhibited endothelial proliferation, a key feature that was absent in the murine models. In all spontaneous and implanted GBMs we found histopathological features compatible with tumor invasion into the non-neoplastic brain parenchyma. Our data indicate that murine models of GBM appear to recapitulate several of the human GBM histopathological features and, considering their reproducibility and availability, they constitute a valuable in vivo system for preclinical studies. Importantly, our results indicate that dog GBM emerges as an attractive animal model for testing novel therapies in a spontaneous tumor in the context of a larger brain.
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PMID:Intracranial glioblastoma models in preclinical neuro-oncology: neuropathological characterization and tumor progression. 1787 37

A 43-year-old woman who had undergone breast cancer surgery 1 year previously complained of headache and nausea. Her brain computed tomography (CT) scan and magnetic resonance imaging (MRI) showed a well-circumscribed, heterogeneously enhanced tumor in the right thalamus. She underwent gross total resection of the tumor followed by radiochemotherapy, and her clinical course was uneventful after surgery. Histological examination revealed a moderate number of tumor cells with fine bipolar processes in a mucoid matrix, which suggested pilocytic astrocytoma. The tumor was associated with microvascular proliferation but did not show significant mitosis or necrosis. In some areas, it had an epithelioid appearance, with ribbon-like, cribriform, and pseudoglandular patterns involving cuboid-shaped cells showing nuclear atypia and mitotic figures. Immunohistochemically, the tumor cells were positive for glial fibrillary acidic protein (GFAP) and vimentin in the area resembling pilocytic astrocytoma, but in the epithelioid area they were negative for GFAP and vimentin as well as for breast cancer markers, including AE1/AE3. The proliferating potential, represented by the MIB-1 labeling index, was high (82.5%) in the area of epithelioid appearance, compared to only 3% in the area of pilocytic astrocytoma-like appearance. As a rare histoarchitectural variant of glioblastoma, the epithelioid pattern may represent a very primitive tumor cell phenotype. Typically, this pattern is characterized by well-circumscribed masses, although its clinical significance is unknown.
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PMID:Epithelioid glioblastoma: a case report. 1809

The anti-neoplastic effects of histone deacetylase inhibitors (HDACi), Trichostatin A (TSA) and 4-phenylbutyrate (4-PB) on the human glioblastoma cell lines GBM-29, U-343 MG and U-343 MGa Cl. 2:6 were investigated. TSA and 4-PB induced apoptosis in the three cell lines in a dose- and time-dependent manner. Whereas caspase-3 activation was detected in all three cell lines, U-343 MG cells were more sensitive to the apoptotic effect of HDACi compared with U-343 MGa Cl. 2:6. TSA and 4-PB induced differentiation in the three cell lines, each cell line developing unique phenotypic characteristics. During long-term treatment with a low dose of HDACi U-343 MGa Cl. 2:6 cells developed an astrocytic morphology with expression of glial fibrillary acidic protein (GFAP). GFAP-negative U-343 MG cells changed their morphology in response to HDACi and down-regulated their expression of vimentin. The nestin and vimentin positive GBM-29 cells also showed a morphological differentiation, while the expression of the two malignancy markers decreased. In summary, our results showed that these three glioblastoma cell lines display unique phenotypes and differentiation patterns in response to HDACi.
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PMID:HDAC inhibitors effectively induce cell type-specific differentiation in human glioblastoma cell lines of different origin. 1836 Jul 9


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