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

Of 26 patients with intramedullary spinal cord gliomas (9 astrocytomas, 5 glioblastomas, 12 ependymomas) seen at the Massachusetts General Hospital from 1962--1980, 24 were irradiated (21 initially and 3 after post-surgical recurrence). Those 19 patients who survived at least 1 year after completion of irradiation were evaluated for post-irradiation neurological changes. No patient developed radiation myelopathy. Return to a permanently and completely normal neurological status occurred for 33/51 (65%) of pre-irradiation neurological deficits. The major cause of post-irradiation neurological deterioration was tumor recurrence. Although 18/19 patients had their thoracic or lumbar spinal cords irradiated, each with field sizes greater than 10 cm, spinal cord doses approaching, equalling, or occasionally exceeding various definitions of spinal cord tolerance were tolerated well without evidence of radiation myelopathy. Spinal cords of patients with intramedullary gliomas, often with major neurological deficits prior to irradiation, may be treated safely to doses approaching or equalling spinal cord tolerance levels. These doses are expected to locally control most ependymomas and astrocytomas without an increased risk of radiation myelopathy. Caution should be observed if doses higher than this are contemplated in an attempt to cure a glioblastoma, because the 5% tolerance level of the damaged spinal cord remains to be defined.
 ...
PMID:Radiation tolerance of the spinal cord previously-damaged by tumor and operation: long term neurological improvement and time-dose-volume relationships after irradiation of intraspinal gliomas. 710 24

We investigated culture supernatants of peripheral blood mononuclear cells (MNC) derived from patients with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) for antiproliferative activity against the human glioblastoma cell line T98G. When T98G cells were cultured with condition medium containing culture supernatants of MNC from patients with HAM, the proliferation of T98G cells was significantly suppressed, compared with that of supernatants from HTLV-I seropositive carriers or seronegative controls. To clarify which population of MNC produced the antiproliferative humoral factor for T98G cells, we separated MNC into macrophage-depleted or B cell depleted populations, and further to both CD4+ and CD8+ T cells by using the panning method or plastic adherence. These studies demonstrated that the antiproliferative activity was mediated by a humoral factor produced by T cells, specifically CD4+ cells. This activity was blocked by a neutralizing monoclonal antibody against interferon-gamma (IFN-gamma). Moreover, IFN-gamma levels were elevated in the culture supernatants of CD4+ cells from HAM patients. Thus, the antiproliferative activity against T98G cells is mainly due to IFN-gamma derived from CD4+ cells of patients with HAM.
 ...
PMID:Antiproliferative factor against the human glioblastoma cell line T98G identified in culture supernatants of CD4+ cells from patients with HTLV-I-associated myelopathy. 791 23

A patient presented with myelopathy due to intramedullary thoracic spinal cord glioblastoma 10 months after treatment for a supratentorial glioblastoma. There was no supratentorial recurrence, and no evidence of gross leptomeningeal dissemination documented by CSF cytology, complete myelography, and MRI imaging. Gross examination of the spinal cord and arachnoid at the time of exploratory thoracic spinal surgery was normal. However, histological review of thoracic arachnoid demonstrated microscopic deposits of glial fibrillary acidic protein (GFAP) positive tumour consistent with malignant astrocytoma. Intramedullary spinal cord metastasis of cerebral glioblastoma rarely occurs, but may develop in association with leptomeningeal tumour dissemination. As local control of primary tumours improves, distant metastasis is likely to become a more common clinical problem. Leptomeningeal gliomatosis may be very difficult to document, even when clinically suspected and GFAP staining of a biopsy of arachnoid tissue can play an important role in confirming the diagnosis. This information can be critical to establish prognosis and develop an appropriate treatment strategy.
 ...
PMID:Supratentorial glioblastoma with spinal cord intramedullary metastasis. 838 62

Using a 51Cr release assay, we investigated Fas-mediated cytotoxicity of peripheral blood CD4+ T cells of patients with human T-lymphotropic virus type-I (HTLV-I)-associated myelopathy (HAM) against T98G, a glioblastoma cell line which expresses Fas. Cytotoxic activity of CD4+ T cells against T98G was significantly higher in HAM patients than in controls. Moreover, when CD4+ T cells of HAM patients were preincubated with a monoclonal antibody to human Fas ligand (FasL), cytotoxic activity against T98G was significantly suppressed. These results suggest that damage to nervous tissues by the Fas/FasL system is involved in the pathogenesis of HAM.
 ...
PMID:Increased Fas-mediated cytotoxicity of CD4-positive T cells in patients with human T-lymphotropic virus type I-associated myelopathy. 966 66

Kallikrein 6 (KLK6) is a secreted serine protease preferentially expressed by oligodendroglia in CNS white matter. Elevated levels of KLK6 occur in actively demyelinating multiple sclerosis (MS) lesions and in cases of spinal cord injury (SCI), stroke, and glioblastoma. Taken with recent evidence establishing KLK6 as a CNS-endogenous activator of protease-activated receptors (PARs), we hypothesized that KLK6 activates a subset of PARs to regulate oligodendrocyte physiology and potentially pathophysiology. Here, primary oligodendrocyte cultures derived from wild type or PAR1-deficient mice and the murine oligodendrocyte cell line, Oli-neu, were used to demonstrate that Klk6 (rodent form) mediates loss of oligodendrocyte processes and impedes morphological differentiation of oligodendrocyte progenitor cells (OPCs) in a PAR1-dependent fashion. Comparable gliopathy was also elicited by the canonical PAR1 agonist, thrombin, as well as PAR1-activating peptides (PAR1-APs). Klk6 also exacerbated ATP-mediated oligodendrogliopathy in vitro, pointing to a potential role in augmenting excitotoxicity. In addition, Klk6 suppressed the expression of proteolipid protein (PLP) RNA in cultured oligodendrocytes by a mechanism involving PAR1-mediated Erk1/2 signaling. Microinjection of PAR1 agonists, including Klk6 or PAR1-APs, into the dorsal column white matter of PAR1(+/+) but not PAR1(-/-) mice promoted vacuolating myelopathy and a loss of immunoreactivity for myelin basic protein (MBP) and CC-1(+) oligodendrocytes. These results demonstrate a functional role for Klk6-PAR1 signaling in oligodendroglial pathophysiology and suggest that antagonists of PAR1 or its protease agonists may represent new modalities to moderate demyelination and to promote myelin regeneration in cases of CNS white matter injury or disease.
 ...
PMID:Critical role for PAR1 in kallikrein 6-mediated oligodendrogliopathy. 2383 58

Extraneural glioblastoma metastases are exceedingly rare, though previously described in the literature. Activating mutations in the BRAF kinase gene (V600E) are present in a minority of glioblastoma patients. Here, we describe a case of systemic metastases of a clonal subpopulation of BRAF V600E mutated glioblastoma in a patient previously treated with surgery, radiation, temozolomide and bevacizumab. The patient presented with a subacute cervical myelopathy during adjuvant treatment. He underwent emergent surgical decompression of an epidural spine metastasis. Analysis of the metastatic tumor demonstrated clonal expansion of a BRAF V600E subpopulation. Though rare, systemic metastasis of glioblastoma should be considered in patients presenting with subacute complaints in line with a mass lesion.
 ...
PMID:A case of epidural glioblastoma metastasis presenting with a cervical myelopathy, torticollis, and L'hermitte's phenomenon. 2974 14