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)

Forty patients with malignant supratentorial gliomas were treated with surgery, intra-arterial infusions of 1-(2-hydroxyethyl)chloroethylnitrosourea, and radiation therapy. The median duration of survival was 12 months; it differed according to the histological subtype (over 30 months for patients with anaplastic astrocytomas or anaplastic oligodendroglioma and 10.5 months for glioblastoma; P = 0.0025). Serious complications of monocular blindness and leukoencephalopathy were observed in four patients (10%).
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PMID:Treatment of malignant gliomas with surgery, intra-arterial infusions of 1-(2-hydroxyethyl)chloroethylnitrosourea, and radiation therapy: a phase II study. 238 41

A 10-year-old boy had a right posterior parietal glioblastoma 5 years after completing treatment for acute lymphoblastic leukemia. Interim findings included seizures, leukoencephalopathy, diffuse mineralizing microangiopathy, and abnormal changes in neuropsychological test performance, which, in retrospect, provided information about the location of the tumor. This case highlights unusual sequelae of childhood leukemia and its treatment, as well as the value of neuropsychological procedures in assessing functional status and integrity of the brain.
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PMID:Serial neuropsychological studies of a child with acute lymphoblastic leukemia and subsequent glioblastoma multiforme. 302 Apr 77

The authors describe the clinical behavior of eight patients with cerebral astrocytomas, in whom computerized tomography (CT) or magnetic resonance (MR) imaging of the brain was characterized by diffuse bilateral cerebral hemisphere tissue density abnormalities and minimal focal mass effect. Five patients were newly diagnosed, and three others had been treated for focal low-grade astrocytoma. Histological diagnoses included anaplastic astrocytoma (three patients), low-grade astrocytoma (three patients), glioblastoma (one patient), and gliosis with later development of glioblastoma (one patient). In five patients, brain tumor was not suspected from the neuroimaging studies, the findings of which were mistaken for radiation leukoencephalopathy, vasogenic edema, or multiple sclerosis. Serial CT scans or MR images undertaken over intervals of 3 to 184 weeks showed progression of abnormal tissue densities in seven patients and multifocal contrast-enhancing masses developed on CT scan in two patients. An autopsy in each of four patients showed diffuse cerebral infiltration by astrocytoma. It is concluded that neuroimaging studies in some patients with diffusely infiltrating cerebral astrocytoma are atypical for neoplasm and can be mistaken for other diseases, especially those that predominantly affect cerebral hemisphere white matter.
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PMID:Diffuse bilateral cerebral astrocytomas with atypical neuroimaging studies. 796 10

"Dementia" is the general term used to describe the symptom complex of intellectual deterioration in adult. Interest in accurately diagnosing dementia is a relatively recent phenomenon. This is reflected in both the development of neuroradiologic examinations, including MRI and SPECT as well as PET, and marked increase in both the incidence and prevalence of dementia associated with increase of the elderly population. The clinical evaluation remains the key to the differential diagnosis. Most cases of "typical dementia" can be diagnosed accurately by clinical criteria. However, the definitive diagnosis of "atypical dementia" still requires intensive neuroradiologic studies and histologic examination of brain to identify characteristic structural changes. In this study, we presented both neuroradiologic and neuropathologic information, which is important in diagnosing diseases that present atypical dementia syndrome. These diseases are as follows; AIDS, isolated CNS angiitis, CO intoxication. Wernicke encephalopathy, adrenoleukodystrophy, Nasu disease, CADASIL, CARASIL, glioblastoma, primary CNS lymphoma, antiphospholipid antibody syndrome, reversible posterior leukoencephalopathy syndrome, mitochondrial encephalopathy (MELAS), and subcortical vascular dementias.
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PMID:[Neuroradiologic and pathologic approaches to the diagnosis of dementia syndrome]. 1037 30

This prospective randomized trial was performed to compare the effectiveness of intra-arterial ACNU with intravenous ACNU in newly diagnosed patients with supratentorial glioblastoma. The primary end points were overall survival and progression-free survival. Within 3 weeks after surgery, patients were randomly assigned to receive either intravenous or intra-arterial ACNU (80 mg/m2) once every 6 weeks concomitant with radiotherapy. Intraarterial ACNU was administered for the first 3 courses followed by intravenous administration. Eighty-four patients were enrolled onto this study and among them 82 patients who passed eligibility criteria were analyzed. Patients characteristics were not different significantly between 2 treatment arms. Median survival and progression-free survival time was 59 and 24 weeks, respectively for intra-arterial arm and 56 and 45 weeks, respectively for intravenous arm. There was no significant difference respectively between two treatment arms. Among the prognostic variables including age, Karnofsky performance status, extent of surgery and treatment arm, Cox's proportional hazards model showed that age was the only significant factor for both survival and progression-free survival (P = 0.003 and 0.016, respectively). With regard to toxicity, there was no significant difference between two treatment arms. Leukoencephalopathy was not observed in intra-arterial arm. In conclusion, intra-arterial ACNU when administered by the method in this study does not increase the survival and progression-free survival of newly diagnosed patients with glioblastoma over that afforded by intravenous ACNU.
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PMID:Randomized comparison of intra-arterial versus intravenous infusion of ACNU for newly diagnosed patients with glioblastoma. 1113 88

Twelve patients with brain tumors and progressive edema caused by tumor progression or radiochemotherapy-related leukoencephalopathy were treated with H15, a phytotherapeutic anti-inflammatory agent. Edema was reduced in two of seven patients with glioblastoma with tumor progression and in three of five patients with treatment-related leukoencephalopathy. All patients with leukoencephalopathy improved clinically for several months.
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PMID:Response of radiochemotherapy-associated cerebral edema to a phytotherapeutic agent, H15. 1134 92

Together with its adaptor protein, the adaptor protein of 12 kDa also known as KARAP and TYROBP (DAP12), triggering receptor expressed in myeloid cells 2 (TREM2) is a stimulatory membrane receptor of the immunoglobulin/lectin-like superfamily, well known in myeloid cells. In humans, however, loss-of-function mutations of TREM2/DAP12 leave myeloid cells unaffected but induce an autosomal recessive disease characterized, together with bone cysts, by a spectrum of pathological lesions in the cortex, thalamus and basal ganglia with clinical symptoms of progressive dementia (polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy). Nothing was known about the role of TREM2/DAP12 in brain cell biology and physiology. By confocal immunocytochemistry we demonstrate that, in both human and mouse cerebral cortex, TREM2/DAP12, strongly expressed by microglia, is also present in a fraction of neurons but not in astrocytes and oligodendrocytes. In contrast, in the hippocampal cortex TREM2-expressing neurons are rare. Both in neurons and microglia the receptor appears to be located mostly intracellularly in a discrete compartment(s) partially coinciding with (or adjacent to) the Golgi complex/trans-Golgi network. Four nerve cell lines were identified as expressing the intracellular receptor system. In living human microglia CHME-5 and glioblastoma T98G cells, activation of TREM2 by its specific antibody induced [Ca2+]i responses, documenting its surface expression and functioning. Surface expression of TREM2, low in resting CHME-5 and T98G cells, increases significantly and transiently (60 min) when cells are stimulated by ionomycin, as revealed by both surface biotinylation and surface immunolabeling. Our results provide the first information about the expression, distribution (mostly intracellular) and functioning of TREM2/DAP12 system in nerve cells, a necessary step in the understanding of the cellular mechanisms affected in polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy.
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PMID:Distribution and signaling of TREM2/DAP12, the receptor system mutated in human polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy dementia. 1554 5

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a progressive cerebral white matter disease with onset in childhood, caused by mutations in the MLC1 gene. MLC1 is a protein with unknown function that is mainly expressed in the brain in astrocytic endfeet at the blood-brain and cerebrospinal fluid-brain barriers. It shares its localization at astrocytic endfeet with the dystrophin-associated glycoprotein complex (DGC). The objective of the present study was to investigate the possible association of MLC1 with the DGC. To test this hypothesis, (co)-localization of DGC-proteins and MLC1 was analyzed by immunohistochemical stainings in gliotic brain tissue from a patient with multiple sclerosis, in glioblastoma tissue and in brain tissue from an MLC patient. In control tissue, a direct protein interaction was tested by immunoprecipitation. Results revealed that MLC1 is co-localized with DGC-proteins in gliotic brain tissue. We demonstrated that both MLC1 and aquaporin-4, a member of the DGC, were redistributed in glioblastoma cells. In MLC brain tissue, we showed absence of MLC1 and altered expression of several DGC-proteins. We demonstrated a direct protein interaction between MLC1 and Kir4.1. From these results we conclude that MLC1 is associated with the DGC at astrocytic endfeet.
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PMID:MLC1 is associated with the dystrophin-glycoprotein complex at astrocytic endfeet. 1762 13

One of the specific forms of progression of malignant tumors of the central nervous system is meningeal dissemination. Meningeal dissemination is a condition in which tumor cells migrate to the brain surface and sub arachnoid space via cerebrospinal fluid and then infiltrate there. This condition can arise from both primary and metastatic brain tumors, with reported incidences of 4.2% for primary tumors and 5.1% for metastatic tumors. Meningeal dissemination frequently arises from germinoma, medulloblastoma, ependymoma and glioblastoma in cases of primary brain tumors and frequently arises from breast cancer, lung cancer and gastric cancer in cases of metastatic brain tumors, known as meningeal carcinomatosis. The prognosis of meningeal dissemination is poor, and conventional treatments such as systemic chemotherapy and radiation therapy are ineffective. Intrathecal infusion of anti neoplastic agents is one of the options for treatment of meningeal dissemination. The advantage of intrathecal chemotherapy is that the anti neoplastic agent is rapidly diffused in the sub arachnoid space, and its duration of activity is long due to its slow clearance and metabolism. Routes of administration include infusion into the lateral ventricle by puncture of the Ommaya reservoir, infusion into the sub arachnoid space by lumbar puncture, or both of these procedures performed alternately or simultaneously, and methods of infusion include bolus injection and ventriculo lumbar perfusion. Commonly used drugs include methotrexate (MTX), cytarabine (Ara-C), and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)- 1-nitrosourea hydrochloride (ACNU), and some new drugs have also begun to be used clinically. Although there are differences depending on the histological type of the tumor, the anti neoplastic agent administered and the method of administration, the response rate is about 40-80% and mean survival time is about 4-25 months. Although side effects of the anti neoplastic agents are not as severe as with agents used for systemic chemotherapy, specific side effects include nonspecific drug-induced meningitis or ventriculitis, transient or permanent paralysis and leukoencephalopathy. These side effects can be alleviated by reducing the dose or discontinuing the anti neoplastic agents, and a small dose of an adrenocorticosteroid is sometimes administered simultaneously. Bacterial meningitis is another complication and requires discontinuation of anti neoplastic agents, removal of the Ommaya reservoir, or systemic or intrathecal administration of antibiotic agents. Although meningeal dissemination is a rare metastatic condition with a poor prognosis, there have been some reports of successful treatment using this method, which is expected to be widely used in the future.
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PMID:[Intrathecal infusion of the antineoplastic agents for meningeal dissemination]. 1863 17

Extended survival of 3 or more years is rare in patients with glioblastoma (GBM) but is becoming more common. Clinical outcome has not been well studied. We reviewed GBM patients at Memorial Sloan-Kettering Cancer Center between 2001 and 2003 who were seen for two or more visits. Patient characteristics and long-term clinical outcomes were reviewed for patients who had survived 3 or more years following diagnosis. Thirty-nine (11%) of 352 GBM patients were identified as long-term survivors. Median survival was 9.15 years (range: 3-18 years). Median age was 47 years (range: 16-69); 13% were 65 years or older. Median KPS was 90 (range: 50-100). One long-term survivor underwent biopsy alone; 19 patients each had either complete or subtotal resection. All received focal radiotherapy (RT) with a median dose of 5940 cGy; 18% received concurrent temozolomide. Adjuvant chemotherapy was administered to 35 (90%). Twelve patients (31%) remained in continuous remission. Twenty-seven had tumor progression a median of 29.2 months after diagnosis (range: 1.2-167 months); 18 had multiple relapses. Median KPS at last follow-up was 70 (range: 40-100); 85% of long-term survivors had at least one significant neurologic deficit. Eleven (28%) had clinically significant RT-induced leukoencephalopathy, 9 (23%) developed RT necrosis and 9 (23%) treatment-related strokes. Treatment-related complications occurred a median of 2.7 years from diagnosis (range: 0.9-11.5 years). Long-term survivors remain rare, but are found across all age groups despite multiple recurrences; clinically significant delayed complications of treatment are common.
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PMID:Neurological outcome of long-term glioblastoma survivors. 1955 99


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