Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty eight human brain tumors: 31 primary glial tumors and 17 metastasizing neoplasms were submitted for an immunocytochemical characterization of mononuclear cell infiltrates in tumor tissue and in its surroundings, with antibodies CD 68, CD45RO, UHCL1, EMB11, CD21 and OPD4. It was found that cells were mainly marked with CD68 and CD45RO, UHCL1. The counting of the marked and unmarked mononuclear cells proved that there is a high degree of variability in cell density which is tumor type and case depended. The results indicate that there were fewer cells which reacted to the antibody EMB11 as compared with cells marked with other antibodies. With CD21 and OPD4 only single cells were marked. A great number of cells remained unmarked. There was a significant difference between the primary glial and the metastatic tumors as far as the number of marked cells is concerned. It is suggested that the difference between primary and metastatic tumors in the number of mononuclear cell infiltrates can be connected with a possibility that the metastatic tumor will present its antigenicity easier as compared with primary tumors of glial origin.
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PMID:Immunocytochemical analysis of cellular infiltrates in primary glial and metastatic tumors in human brain. 836 11

Interleukin 10 (IL-10) expression has been found to be correlated with the extent of malignancy in gliomas. In vitro, IL-10 increases proliferation and migratory capacity in human glioma cell lines. In this study, we localized the site of IL-10 synthesis in gliomas to cells of microglial origin. Biopsy specimens from 11 patients with malignant glioma were processed on native tissues and at early cell culture passages (0-4). IL-10 mRNA was analyzed by RT-PCR and in situ hybridization. Protein was quantitatively assessed by ELISA in cell culture supernatants, and cells expressing IL-10 were determined by a combination of immunohistochemistry for CD68 (specific for microglia/macrophage lineage) and IL-10 in situ hybridization. IL-10 mRNA decreased from passage 0 to 4 in all samples and was undetectable beyond passage 5. Such downregulation of mRNA leads to a steep decrease of IL-10 protein in culture supernatants (below detection level, 0.05 ng/ml, beyond passage 1). The combination of in situ hybridization for IL-10 and CD68 immunostaining revealed that only cells of the microglia/macrophage lineage produced IL-10 mRNA. Our results identify microglia/macrophage cells as the major source of IL-10 expression in gliomas which decreases markedly during early passages of primary cultures of human gliomas due to a progressive reduction of microglia/macrophages present.
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PMID:Microglial/macrophage expression of interleukin 10 in human glioblastomas. 1036 Aug 13

Herpes simplex virus thymidine kinase (HSV-tk) gene transfer and ganciclovir (GCV) administration have been suggested for the treatment of malignant gliomas. To understand tissue responses and possible ways to improve the treatment effect, we studied tumor growth, tissue reactions, and survival time after HSV-tk/GCV treatment in a syngeneic BT4C rat glioma model by mixing various ratios of stably transfected HSV-tk-expressing BT4C-tk glioma cells with wild-type BT4C glioma cells (percentage of BT4C-tk cells: 0%, 1%, 10%, 30%, 50%, and 100%), followed by injection into BDIX rat brains (n = 79). With the exception of some animals with end-stage tumors, very little astroglia or microglia reactivity was detected in the wild-type tumors as analyzed by immunocytochemistry using glial fibrillary acid protein (GFAP)-, vimentin-, human histocompatibility leukocyte antigen-DR-, OX-42-, and CD68-specific monoclonal antibodies. After 14 days of GCV treatment, tumors induced with > or = 10% BT4C-tk cells showed a significant reduction in tumor size (P < .05) and prolonged survival time (P < .01). Astrogliosis, as indicated by a strong GFAP and vimentin immunoreactivity, was seen in the tumor scar area. GFAP and vimentin reactivity was already present after the GCV treatment in tumors induced with 1% BT4C-tk cells. Much less human histocompatibility leukocyte antigen-DR-positive microglia was seen in the treated animals, indicating low microglia reactivity and immunoactivation against the tumor. However, GCV-treated tumors were positive for apoptosis, indicating that apoptosis is an important mechanism for cell death in the BT4C-tk glioma model. Our results suggest that > or = 10% transfection efficiency is required for a successful reduction in BT4C glioma tumor size with HSV-tk/GCV treatment in vivo. Tissue reactions after 14 days of GCV treatment are characterized by astrogliosis and apoptosis, whereas microglia response and immunoactivation of the brain cells appear to play a minor role. Stimulation of the microglia response by gene transfer or other means might improve the efficacy of the HSV-tk/GCV treatment in vivo.
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PMID:Herpes simplex virus thymidine kinase gene therapy in experimental rat BT4C glioma model: effect of the percentage of thymidine kinase-positive glioma cells on treatment effect, survival time, and tissue reactions. 1076 47

Human central nervous system tumors and glioma cell lines highly express the insulin-like growth factor-binding protein (IGFBP)-2. As IGFBP-2 can affect tumor growth, we studied the relationship between IGFBP-2 expression and the malignancy of brain tumors in vivo. To do so, we investigated by immunohistochemistry the accumulation of IGFBP-1, -2, and -3 in 50 human gliomas classified by the WHO Malignancy Scale. Double labeling using anti-CD68 (monocytes/macrophages), antiglial fibrillary acidic protein, and anti-CD3 (T cells) antibodies was performed to further characterize the IGFBP-1, -2, and -3(+) cells. The expression of IGFBP messenger RNAs (mRNAs) was tested by RT-PCR in tumor samples from nine gliomas of different grades and in eight cell lines representing the cellular composition of human glioma. As controls, the accumulation of IGFBP-2 was investigated in normal brain and in the rat C6 glioblastoma model. IGFBP-1 and -3 accumulated in endothelial and macrophage/microglial cells. IGFBP-2(+) macrophage/microglial and glioma cells clustered in the immediate vicinity of focal necrosis of the human gliomas as well as of the rat C6 glioblastoma. The labeling score of IGFBP-1 accumulation in endothelial cells correlated negatively (P: = 0.0229), and that of IGFBP-2 accumulation in glioma cells correlated positively (P: < 0.0006) with the tumor grade of the gliomas. In addition, RT-PCR analysis confirmed mRNA expression of IGFBP-1, -2, and -3 by the gliomas and glial cells. Small amounts of IGFBP-1 and -3 mRNA, but high amounts of IGFBP-2 mRNA, were detectable in macrophage-like and glioma cell lines. The results suggest cell type-specific accumulation of IGFBP-1, -2, and -3 in human glial tumors of the brain. The increase in IGFBP-2 expression with this malignancy suggests a role of IGFBP-2 in the biology of human gliomas.
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PMID:In vivo expression of insulin-like growth factor-binding protein-2 in human gliomas increases with the tumor grade. 1125 Sep 47

Scatter factor/hepatocyte growth factor (SF/HGF) is a pleiotropic cytokine that has been implicated in glioma invasion and angiogenesis. The SF/HGF receptor, MET, has been found to be expressed in neoplastic astrocytes as well as in endothelial cells of the tumor vasculature. Both SF/HGF and MET expression have also been described to correlate with the malignancy grade of human gliomas. However, most glioblastoma cell lines lack SF/HGF expression, raising the question of the cellular origin of SF/HGF in vivo. Using in situ hybridization, we analyzed glioblastomas, anaplastic astrocytomas, diffuse astrocytomas, pilocytic astrocytomas, and normal brain for the expression of SF/HGF mRNA. We detected strong SF/HGF expression by the majority of the tumor cells and by vascular endothelial cells in all glioblastoma specimens analyzed. Combined use of in situ hybridization with fluorescence immunohistochemistry confirmed the astrocytic origin of the SF/HGF-expressiong cells. In contrast, CD68-immunoreactive microglia/macrophages, as well as vascular smooth muscle cells reactive to alpha-smooth muscle actin, lacked SF/HGF expression. In anaplastic, diffuse, and pilocytic astrocytomas, SF/HGF expression was confined to a subset of tumor cells, and signals were less intense than in glioblastomas. In addition, we detected SF/HGF mRNA in cortical neurons. SF/HGF expression was not up regulated around necroses or at tumor margins. MET immunoreactivity was observed in GFAP-expressing astrocytic tumor cells and endothelial cells as well as in a subset of microglia/macrophages. We conclude that in vivo, both autocrine and paracrine stimulation of tumor cells and endothelium through the SF/HGF-MET system are likely to contribute to tumor invasion and angiogenesis. Lack of SF/HGF expression by most cultured glioblastoma cells is not representative of the in vivo situation and most likely represents a culture artifact.
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PMID:Expression and localization of scatter factor/hepatocyte growth factor in human astrocytomas. 1129 84

In order to elucidate the reason for conflicting results that have been published previously on galectin-3 expression in human gliomas, we used single labeling and double labeling immunohistochemistry experiments to identify cellular origin and extent of galectin-3 positivity in 53 glioma-samples (16 glioblastomas, 21 anaplastic astrocytomas, 16 low-grade astrocytomas). Galectin-3 positivity was observed in neoplastic astrocytes, macrophages/microglial cells. endothelial cells and some B- and T-lymphocytes. The quantitative analysis showed that the percentage of galectin-3 positive cells was significantly higher in the tumor parenchyma of glioblastomas than in anaplastic (p = 0.0371) and low-grade astrocytomas (p = 0.0042). Single labeling with anti-CD68 antibodies revealed a significant correlation between CD68 and galectin-3 immunoreactivity (p = 0.0092). Endothelial cells were labeled in all low-grade and anaplastic astrocytomas, but only in 10/16 glioblastomas (p = 0.0003). This detailed analysis demonstrates that galectin-3 positivity in human gliomas is considerably influenced by tumor-infiltrating macrophages. The differential expression on endothelial cells raises the question if galectin-3 plays a role in tumor angiogenesis of human gliomas.
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PMID:Galectin-3: cellular distribution and correlation with WHO-grade in human gliomas. 1167 25

Demyelinating disease presenting as a solitary contrast-enhancing mass poses a diagnostic challenge for both radiologists and surgical pathologists. We report the cases of two female patients, aged 23 and 37 years, who exhibited the clinical and radiologic features of a space-occupying mass strongly suggestive of neoplasia. In both patients, magnetic resonance imaging showed a ring-enhancing parietal lesion. Intraoperative frozen sections in both patients displayed histologic features strongly suggestive of a glial neoplasm, including marked hypercellularity, a prominent astrocytic component, and easily identifiable mitotic figures. However, permanent sections showed additional and helpful histologic findings that included Creutzfeldt astrocytes and granular mitoses. Subsequent immunostaining showed that the hypercellularity was principally caused by macrophage infiltration (HAM-56 and CD68) and an associated reactive astrocytosis (glial fibrillary acidic protein). Additional confirmatory tests included special stains for myelin (Luxol-fast-blue), which demonstrated focal, sharply marginated loss of myelin, and for axons (silver stain for axons and neurofilament protein immunohistochemistry), which showed relative preservation of axons in areas of myelin loss. Together, the special stains confirmed the demyelinating nature of the lesions. The keys to avoiding misdiagnosing a demyelinating pseudotumor as a diffuse glioma include a general awareness of this potential pitfall, including the radiologic appearance of demyelinating pseudotumors as contrast-enhancing solitary masses that mimic tumor; knowledge of the characteristic histologic features, including Creutzfeldt astrocytes and granular mitoses; and a high index of suspicion for macrophage infiltration combined with a willingness to use appropriate confirmatory immunohistochemical studies in suspicious or uncertain cases. This approach will minimize the chance of misdiagnosis and subsequent use of inappropriate and deleterious therapies.
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PMID:Demyelinating pseudotumor. 1237 18

CD14 is a membrane-bound lipopolysaccharide receptor or, lacking the glycosylphosphatidylinositol anchor, is secreted to modulate cellular and humoral immune response by interacting directly with T and B cells. Because immunodepletion is thought to contribute to the grim prognosis of glioblastoma patients, we analyzed expression and release of CD14 in rat and human astrocytomas and glioma cell lines. Immunohistochemistry of 50 glioma biopsy specimens from low-grade diffuse astrocytoma (WHO grade II), anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV), and of the C6 rat glioma model demonstrated significantly more CD14-immunoreactive macrophages/microglial cells in glioblastomas than in less malignant gliomas. In WHO grade II and III astrocytomas, only perivascular cells showed immunoreactivity with CD14. In glioblastomas, CD14-immunoreactive cells were mainly found scattered throughout the entire tumor parenchyma. Double labeling experiments demonstrated CD14 immunoreactivity predominantly in CD68-expressing macrophages/microglial cells and some glioma cells. Western blotting, reverse transcription-PCR and consecutive sequencing confirmed expression and release of CD14 by four of six analyzed glioma cell lines. These results demonstrate that CD14 is expressed, and more importantly released, from a subset of human glioma cells and infiltrating macrophages/microglial cells that may contribute to immunodepletion observed in these patients.
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PMID:Expression and release of CD14 in astrocytic brain tumors. 1283 48

Although the expression O6-methylguanine-DNA methyltransferase (MGMT) is an important hallmark for decision of nitrosourea chemotherapy for glioma patients, no immunohistochemical method for analysis of MGMT has been standardized yet. Gliomas usually contain non-neoplastic cells even deep in the tumor. It is not known which of these components expresses MGMT. To clarify this point, we investigated MGMT expression in the non-neoplastic cells in autopsy and surgical specimens by immunohistochemistry. High grade gliomas were also studied to find a cut-off point for treatment decision. MGMT immunohistochemistry in the normal brain or brain with non-neoplastic disease revealed nuclear staining in some endothelial cells, inflammatory cells, ependymal cells, astrocytes and oligodendroglias. Some cells were double stained with CD68 (macrophages or microglias). The neurons were consistently MGMT-negative. High grade gliomas always contained an MGMT-positive non-neoplastic component. Although, the endothelial cells were easily distinguished from the neoplastic cells, other cells were often mistaken for tumor cells. The population of MGMT-positive non-neoplastic cells was usually less than 10%. We set a cut off-point at 10% between the positive and negative groups because the statistical difference in the overall survival was most distinct at this value. In 51 high grade glioma patients, who received both radiotherapy and chemotherapy with nimustine (ACNU), the median overall survival of the MGMT-negative group (23 months) was significantly longer than that of the MGMT-positive group (14 months) (P < 0.009). Multivariate analysis revealed that the negative MGMT expression was a significant prognostic variable next to the degree of surgical removal for the overall survival. In the MGMT-positive group, addition of platinum-based chemotherapy did not improve the survival.
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PMID:Immunohistochemical study for O6-methylguanine-DNA methyltransferase in the non-neoplastic and neoplastic components of gliomas. 1566 74

Gliomas are the most common intrinsic brain tumors. The degree of vascularization corresponds to malignancy and is related to prognosis. In order to retrieve information about tumor behavior in situ, the use of primary tissue material for experiments is advantageous. With increasing evidence for the importance of microenvironment and vascularization in tumor biology, we concentrated on the isolation of endothelial cells (EC) from primary tumor material to investigate the role of endothelium within tumor tissue. We developed a method for isolation and purification of tumor-derived endothelial cells. EC were isolated and cultivated from normal brain using tissue digestion and Percoll density gradient centrifugation resulting in a <95% of EC culture. For isolation of EC from gliomas of different malignancy grades a combination of tissue digestion, Percoll gradient centrifugation and magnetic bead sorting by anti-CD31, -VE-Cadherin and -CD 105 was employed. This approach provided a purity of <98%. Cells were classified and characterized by testing expression of CD105, CD31, VE-Cadherin, vWF, UEA-1 and measuring DiI-Ac-LDL-uptake. To exclude contamination, staining and negative selection with anti-SMA, -GFAP, and -CD68 was performed. Tumors were histopathologically diagnosed according to WHO classification. We isolated EC from normal brain (NBEC, n = 11), low-grade gliomas WHO II (LGEC, n = 22), and high-grade gliomas WHO III & IV (HGEC, n = 11). There were no clear differences in EC morphology between the different tumor grades. However, a significantly higher proliferation rate of HGEC compared to LGEC was observed as well as distinctive antigen expression. Already in early passages isolated EC showed a rapid change in antigen expression indicating a phenotypic shift under culture conditions. We could establish a protocol for reliable and reproducible isolation and culture of EC from gliomas with different WHO grading. In first phenotypical and functional analyses, NBEC, LGEC and HGEC show remarkable differences. EC from all tumors could be grown in culture. However, passage related changes of EC phenotype demand very early passages to work with.
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PMID:Isolation and culture of microvascular endothelial cells from gliomas of different WHO grades. 1615 23


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