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)

Gliomas very rarely arise from the leptomeninges. They can be both solitary and diffuse, and histological examination reveals mostly astrocytic tumors. The authors report a case (the 12th reported in the literature) of a solitary primary glioma of the leptomeninges in a 79-year-old man who presented with repeated seizures. A magnetic resonance image revealed an ill-defined enhancing lesion in the cerebral meninges. Autopsy examination showed a poorly demarcated astrocytoma in the sylvian fissure infiltrating the adjacent subarachnoid space. The literature concerning primary leptomeningeal glioma is reviewed.
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PMID:Primary leptomeningeal astrocytoma. Case report. 948 17

A rare case of glioblastoma fed by meningeal branches of the external carotid artery was reported. A 63-year-old female was transferred to our hospital suffering from gait disturbance and dysarthria. CT and MRI revealed brain tumor and paratumoral hemorrhage with a large cyst that was heterogeneously enhanced and existed in the right fronto-temporal region. Right external carotid arteriography demonstrated the tumor stain markedly fed by the right middle meningeal artery and the accessory meningeal artery. Subtotal removal operation was carried out uneventfully using the right fronto-temporal craniotomy. The histological diagnosis was glioblastoma. After the operation the patient was in good condition, and was transferred to another hospital for the purpose of the synchronized chemoradiotherapy. It is well known that any glioma invades the meninges. However, we rarely encountered an intra-axial glioma fed by a meningeal blood supply. A meningeal-invaded glioma may make difficult its differentiation from meningioma. We concluded that there is necessity for close examination of the intra-axial brain tumors invaded and fed by meningeal blood supply.
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PMID:[Glioblastoma fed by meningeal branches of the external carotid artery: a case report]. 1036 56

Various proteases and their inhibitors have been shown to be important in tumor invasion. Angiogenesis is further a prerequisite for the growth and progression of solid tumors. Since these systems are functionally linked, in situ hybridization and in situ zymography were used to investigate the spatial and temporal expression of factors representative of the plasmin/plasminogen system and of an angiogenic factor in the BT4C glioma model. This tumor is invasive with a high grade of neovascularization. Tissue-type plasminogen activator urokinase-type plasminogen activator and plasminogen activator inhibitor-1 mRNA were expressed in glioma cells during the entire tumor growth. Early in the tumor development the expression was found throughout the small tumor (approximately 10 mm3) while later in the time course the expression was found predominantly in the invasive tumor border of the tumor. The in situ zymography demonstrated that the plasminogen activators were translated into functional proteins. Vascular endothelial growth factor mRNA was expressed following a similar spatial and temporal pattern with an early expression in the entire small tumor while later, in larger tumors, it was exclusively expressed in the invasive tumor edge. In normal brain, the ventricular ependyma, meninges, as well as scattered neurons expressed tissue-type plasminogen activator mRNA. Vascular endothelial growth factor mRNA was observed in the choroid plexus, and in scattered cells in normal brain tissue. Our finding may suggest a functional co-operation of tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor-1 and vascular endothelial growth factor during glioma progression. This model could be of value when evaluating different treatment modalities aimed at blocking the migrating capacity and growth of glial tumors.
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PMID:Expression of the proteolytic factors, tPA and uPA, PAI-1 and VEGF during malignant glioma progression. 1057 9

Angiogenesis and extracellular matrix degradation are key events in tumour progression, and factors regulating stromal-epithelial interactions and matrix composition are potential targets for the development of novel anti-invasive/antiangiogenic therapies. Here, we examine the expression of ADAMTS-8, a secreted protease with antiangiogenic properties, in brain tissues. Using quantitative RT-polymerase chain reaction (PCR), high, equivalent expression of ADAMTS-8 was found in normal whole brain, cerebral cortex, frontal lobe, cerebellum and meninges. ADAMTS-8 expression in 34 brain tumours (including 22 high-grade gliomas) and four glioma cell lines indicated at least two-fold reduction in mRNA compared to normal whole brain in all neoplastic tissues, and no detectable expression in 14 out of 34 (41%) tumours or four out of four (100%) cell lines. In contrast, differential expression of TSP1 and VEGF was seen in nine out of 15 (60%) and seven out of 13 (54%) tumours, with no relationship in the expression of these genes. Immunohistochemistry and Western analysis indicated downregulation of ADAMTS-8 protein in >77% tumours. Methylation-specific PCR analysis of ADAMTS-8 indicated promoter hypermethylation in one out of 24 brain tumours (a metastasis) and three out of four glioma cell lines suggesting an alternative mechanism of downregulation. These data suggest a role for ADAMTS-8 in brain tumorigenesis, warranting further investigation into its role in regulation of tumour angiogenesis and local invasion.
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PMID:Expression of ADAMTS-8, a secreted protease with antiangiogenic properties, is downregulated in brain tumours. 1657 50

The calcium-binding Mts1/S100A4 protein plays an important role in motility and metastatic activity of tumor cells. Recently we showed that Mts1/S100A4 is expressed in white matter astrocytes and influences their migration in vitro and in vivo. Here, we have investigated the role of Mts1/S100A4 expression in C6 glioma cells or surrounding astrocytes for migration of C6 cells on astrocytes, using short interference (si) RNA to silence Mts1/S100A4 expression. We find that in vitro, the migration of Mts1/S100A4 expressing and silenced C6 cells on astrocytes is predominantly dependent on the expression of Mts1/S100A4 in astrocytes, i.e. C6 cells preferably migrate on Mts1/S100A4-silenced astrocytes. In vivo, Mts1/S100A4-positive C6 cells preferably migrate in white matter. In contrast Mts1/S100A4-silenced C6 cells avoid white matter and migrate in gray matter and meninges. Thus, the migration pattern of C6 cells is affected by their intrinsic Mts1/S100A4 expression as well as Mts1/S100A4 expression in astrocytes. To investigate if Mts1/S100A4 has a significant role on brain tumor progression, we made quantitative RT-PCR analysis for the expression of S100A4/Mts1 in various grades of astrocytic tumors. Our data showed that high-grade glioblastomas express higher amount of S100A4/Mts1 than low-grade astrocytic tumors.
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PMID:Modified expression of Mts1/S100A4 protein in C6 glioma cells or surrounding astrocytes affects migration of tumor cells in vitro and in vivo. 1722 48

The four GPI-anchored cell adhesion molecules that exemplify the IgLON family are most highly expressed in the nervous system and associate to form up to six different heterodimeric 'Diglons' that can modify cell adhesion and inhibit axon migration. Recently, two members, OPCML and LSAMP, were identified as putative tumour suppressor genes in ovarian and renal carcinomas respectively. In this study, we investigated OPCML expression in nonneoplastic brain tissue and 35 brain tumours (18 glioblastoma multiformes, five anaplastic gliomas, five meningiomas, six metastases and one medulloblastoma) and four glioma cell lines using quantitative reverse transcriptase polymerase chain reaction (RT-PCR). OPCML was highly expressed in cerebellum, less so in cerebral cortex, frontal lobe and meninges and was significantly reduced or absent in 83% of brain tumours and all cell lines compared with nonneoplastic whole brain. Two OPCML splice variants have been identified in humans, termed alpha1 and alpha2, but the latter has not been demonstrated in human neural tissues. Using PCR with specific primers, nonneoplastic brain and 3/6 of tested brain tumours expressed both splice variants, whereas the remaining brain tumours only expressed the alpha2 variant. Hypermethylation of the alpha1 OPCML promoter, associated with down-regulation of expression in ovarian tumours, did not correlate with expression levels in the subset of brain tumours tested, implying transcription of OPCML from an alternative promoter or a different mechanism of down-regulation. This study demonstrates that OPCML down-regulation occurs in the majority of brain tumours tested, warranting further investigation of OPCML and other IgLONs in the development and progression of brain tumours.
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PMID:Expression of cellular adhesion molecule 'OPCML' is down-regulated in gliomas and other brain tumours. 1723 10

Medulloblastoma spreads by leptomeningeal dissemination rather than by infiltration that characterizes other CNS tumors, eg, gliomas. This study represents an initial attempt to identify both the molecules that mediate medulloblastoma adhesion to leptomeninges and the pathways that are key to survival and proliferation of tumor following adhesion. As a first step in molecule identification, we produced adhesion of D283 medulloblastoma cells to the extracellular matrix (ECM) of H4 glioma cells in vitro. Within this context, D283 cells preferentially expressed the alpha9 and beta1 integrin subunits; antibody and disintegrin blockade of alpha9 and beta1 binding eliminated the adhesion. The H4 ECM was enriched in tenascin, a binding partner for the alpha9beta1 integrin heterodimer. Purified tenascin-C supported D283 cell adhesion. The adhesion was blocked by antibodies to alpha9 and beta1 integrin. In vivo data were similar; immunohistochemistry of primary human medulloblastomas with leptomeningeal extension demonstrated increased expression of alpha9 and beta1 integrins as well as tenascin at the interface of brain and leptomeningeal tumor. These data suggest that tumor-cell expressions of alpha9 and beta1 integrins in combination with extracellular tenascin are necessary for medulloblastoma adhesion to the leptomeninges. As a first step in the identification of pathways that mediate survival and proliferation of tumor following adhesion, we demonstrated that adhesion to H4 ECM was associated with survival and proliferation of D283 cells as well as activation of the MAPK pathway in a growth factor deficient environment. Antibody blockade of alpha9 and beta1 integrin binding that eliminated adhesion also eliminated the in vitro survival benefit. These data suggest that adhesion of medulloblastoma to the meninges is necessary for the survival and proliferation of these tumor cells at the secondary site.
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PMID:Integrins mediate adhesion of medulloblastoma cells to tenascin and activate pathways associated with survival and proliferation. 1879 52

Several different types of tumors, benign and malignant, have been identified in the central nervous system (CNS). The prognoses for these tumors are related to several factors, such as the age of the patient and the location and histology of the tumor. In adults, about half of all CNS tumors are malignant, whereas in pediatric patients, more than 75% are malignant. For most benign CNS tumors that require treatment, neurosurgeons can offer curative resections or at least provide significant relief from mass effect. Unfortunately, we still lack effective treatments for most primary and secondary malignant CNS tumors. However, the past decade has witnessed an explosion in the understanding of the early molecular events in malignant primary CNS tumors, and for the first time in history, oncologists are seeing that a plethora of new therapies targeting these molecular events are being tested in clinical trials. There is hope on the horizon for the fight against these deadly tumors. The distribution of CNS tumors by location has remained constant for numerous years. The majority of primary CNS tumors arise in the major cortical lobes. Twenty nine percent of primary CNS tumors arise from the dural meninges that encase the CNS structures. The vast majority of these are meningiomas, of which over 90% are benign. About 10% of primary CNS tumors are found in the sella turcica region, where the pituitary gland resides. Other much less common sites of primary CNS tumors include the pineal region, ventricular system, cerebellum, brain stem, cranial nerves, and spinal cord. The distribution of CNS tumors by histology has seen a slight increase in more malignant tumors over the past decade, possibly due to increased neuroimaging practices or environmental exposures. Arising from glial cells, gliomas represent over 36% of all primary CNS tumors and consist of astrocytomas, oligodendrogliomas, ependymomas, mixed gliomas, and neuroepithelial tumors. The benign meningiomas make up 32% of primary CNS tumors, followed by nerve sheath tumors and pituitary tumors. Primary CNS lymphomas, embryonal tumors, and craniopharyngiomas are uncommon. The most common gliomas are astrocytomas, and these tumors are typically classified by the World Health Organization (WHO) as Grades I through IV. Grade IV, the most malignant grade of astrocytoma, includes glioblastoma multiforme (GBM), the most common malignant primary CNS glioma in adults, which represents 51% of all CNS gliomas. GBM is unfortunately the most challenging to effectively treat and has the worst patient survival. This chapter is therefore primarily devoted to the current understanding of this topic. Here we describe the molecular and cellular events associated with malignant glioma initiation and progression. We also review the importance of glioma stem cell biology and tumor immunology in early gliomagenesis. In addition, we present a brief description of the most common malignant primary CNS glioma in pediatric patients - medulloblastoma, as well as familial cancer syndromes that include gliomas as part of the syndrome.
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PMID:Central nervous system. 2211 77

Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare condition, characterized by infiltration of the meninges by glial cells without evidence of the primary tumor in the brain or spinal cord parenchyma. Glioma arising primarily from the leptomeninges is extremely rare and often diagnosed only in post mortem examination and the diagnosis may be missed in meningeal biopsy. We describe a young female who presented with symptoms of raised intracranial pressure with imaging evidence of diffuse leptomeningeal enhancement in whom autopsy confirmed the diagnosis of PDLG. Our case illustrates the diagnostic difficulties in making the pre-mortem diagnosis even with multiple cerebrospinal fluid cytologies and leptomeningeal biopsy.
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PMID:Primary diffuse leptomeningeal gliomatosis: An autopsy case report. 2502 82

Undifferentiated brain tumors represent a diagnostic challenge, particularly in small biopsies, with regards to their primary versus metastatic origin. The latter may show overlapping morphologic features with primary high-grade brain tumors. In recent years several new antibodies have entered the realm of daily pathology practice. PAX8 (mammalian paired box genes 1 to 9 protein encoding gene) is among these new markers and is recognized as a differentiating marker of the primary site in epithelial tumors outside of the central nervous system. A review of the literature shows lack of site-specific studies with regards to the expression of PAX8 in the central nervous system and its neoplasms. Using this marker we investigated its immunohistochemical expression in normal brain tissue and glial tumors. The immunostain was performed on tissue microarrays of 71 cores from 24 cases. We also performed PAX8 immunostain on sections from cerebellum, pons, periventricular ependymal layer, choroid plexus, pituitary, and meninges of 3 autopsy cases. Our results indicate lack of PAX8 expression by benign brain tissue. Only 1 glioblastoma core (1/9 cores) showed focal nuclear reactivity with the antibody. Our results indicate that presence of PAX8 immunoreactivity in an undifferentiated brain tumor lacking gliofibrillary acidic protein expression should prompt consideration of a metastatic tumor.
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PMID:Evaluation of PAX8 Expression in Brain Tissue and Related Neoplasms. 2637 31


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