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)

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

Interleukin-1 (IL-1) plays a controversial role in the immune response. Besides its activation of immune cells and juvenile central nervous system cells, monocyte-derived IL-1 may be able to stimulate the malignant transformation and proliferation of glial brain tumor cells expressing IL-1 receptors. The aim of this study was to determine the growth pattern and the IL-1 beta release of long-term cultured peripheral blood monocytes of glioma patients. At 6- to 7-day intervals, the vital monocytes, characterized by CD14 immunophenotyping, were counted. By the use of a specific IL-1 beta enzyme-linked immunosorbent assay, the IL-1 beta content of monocyte culture supernatants derived from 13 subjects with glioma and from 12 controls were compared at Days 7, 21, and 100 of culture. Cell clusters of monocytes derived from glioblastoma patients survived more than 250 days in culture, whereas control monocytes survived only up to 114 days. The IL-1 beta release of glioma-associated peripheral blood monocyte cultures was about 50 times higher as compared with control monocyte cultures. Dexamethasone treatment at the time of blood sampling and recurrences of the gliomas did not influence the increase in the IL-1 beta expression of glioma monocytes. It seemed that at least subsets of glioma-associated blood monocytes, although they had been removed from the circulation, remained activated for a long period of time. We conclude that increased IL-1 beta production of glioma-associated peripheral blood monocytes and their longevity in vitro may be features of aberrant immune cell subsets. In future studies, the exact phenotyping of monocyte subsets will be mandatory.
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PMID:Enhanced interleukin-1 beta release and longevity of glioma-associated peripheral blood monocytes in vitro. 796 34

Human glioblastoma (U-87MG) and canine glioma (canine brain tumor [CBT]) cell lines were tested in vitro for their therapeutic sensitivity to sequential treatment with differentiating agents and chemotherapy or hyperthermia. Both cell lines responded to the inducer combination dibutyryl adenosine-3',5'-cyclic monophosphate/sodium butyrate by the formation of cytoplasmic processes detectable within 7 hours and attained approximately 90% morphological differentiation within 2 days of exposure. The clonogenicity of CBT and U-87MG cells gradually decreased after 1 to 7 days of exposure to the inducer combination, but this treatment alone failed to kill the cells. After the removal of the inducers, both lines dedifferentiated and the rate of clonogenesis increased. 1,3-bis-(2-Chloroethyl)-1-nitrosourea administered to CBT and U-87MG cells before or after 3 days of treatment with inducers potentiated the antiproliferative effects of the differentiating agents. Cisplatin administered to U-87MG cells enhanced the antiproliferative effect of the differentiating agents to a greater extent when added before the inducers rather than after differentiation was stimulated. The sequential treatment of CBT cells with a 44 degrees C heat pulse for 30 minutes followed by differentiating agents produced an additive potentiation of cell killing, whereas the reverse sequence did not. Hyperthermia pretreatment at 44 degrees C for 15 minutes or at 42 degrees C for 30 minutes failed to enhance the antiproliferative effects of inducing agents.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differentiation therapy is potentiated by chemotherapy and hyperthermia in human and canine brain tumor cells in vitro. 800 63

Anti-homocysteate antibodies with postembedding immunohistochemistry for light microscopy were used to localize homocysteate-like immunoreactivity in human multiform glioblastoma. The most remarkable stained elements (6.8% of the total tumoral tissue) corresponded to distinct astrocytic cell bodies, intermingled fibrous processes and puncta of diverse size, some of them closely apposed to capillaries. In not affected peritumoral tissue, on the other hand, numerous labelled dots resembling portions of glial processes were observed in the neuropil and around blood vessels (2.7% of the total peritumoral tissue). However, glial and neuronal cell bodies could not be detected. These observations extend to a human brain tumor of glial nature the knowledge on the preferential localization of homocysteate in glia.
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PMID:Homocysteate-like immunoreactivity in multiform glioblastoma of human brain. 802 91

Temozolomide, a methylating agent with clinical activity against brain tumors, demonstrated excellent antitumor activity following p.o. administration to athymic mice bearing human brain tumor xenografts. In the early stage s.c. implanted SNB-75 astrocytoma model, a 400-mg/kg dose administered on Day 5 produced 10 of 10 Day 54 tumor-free mice. In later staged s.c. U251 and SF-295 glioblastoma models, a single 600-mg/kg dose produced 9 of 10 Day 86 and 2 of 10 Day 40 tumor-free mice, respectively. In the latter group, a tumor growth delay of > 315% was attained. Similar levels of activity were attained with equal total doses on schedules of daily for 5 doses and every fourth day for 3 doses. A single 40-mg/kg i.v. dose of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) also demonstrated excellent activity, producing 9 of 10 tumor-free mice in the SNB-75 model and growth delays of 283 and 301% in the U251 and SF-295 models, respectively. Temozolomide was also highly effective against intracerebral implants of the U251 and SF-295 glioblastomas. Administration of either 600 mg/kg on Day 1 or 200 mg/kg on Days 1, 5, and 9 produced 7 of 9 Day 90 tumor-free mice in the U251 model. In the SF-295 model, a single 400-mg/kg dose or three 200-mg/kg doses produced 3 and 4 of 10 Day 90 tumor-free mice, respectively, and prolonged survival by 127%. A single 40-mg/kg i.v. dose of BCNU was more effective than temozolomide in the intracerebral SF-295 model, and less effective in the intracerebral U251 model. The synergistic potential of temozolomide and BCNU in combination was evaluated in an advanced stage s.c. implanted SF-295 model. When temozolomide was administered 2 h after BCNU on a single treatment day, a dramatic synergistic therapeutic effect was observed in two experiments. For example, single agent doses of temozolomide (600 mg/kg) and BCNU (60 mg/kg) and a combination (400 mg/kg + 27 mg/kg) demonstrating equivalent toxicity produced growth delays of 190, 258, and > 492% (includes 5 of 10 Day 51 tumor-free mice), respectively. Analysis of the data by a quadratic dose response model indicated synergism with significance at P = 0.0001 in both experiments. Synergism also was demonstrated by the isobole method. The reverse sequence was more toxic, but at lower combination doses a synergistic effect was still observed (P = 0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Preclinical antitumor activity of temozolomide in mice: efficacy against human brain tumor xenografts and synergism with 1,3-bis(2-chloroethyl)-1-nitrosourea. 803 99

Glioblastoma is the most malignant primary brain tumor. Inhibition of angiogenesis is one potential strategy for treating this fatal hypervascular tumor. AGM-1470 (also called TNP-470), a novel, potent, fungus-derived inhibitor of angiogenesis, was tested on the growth of human glioblastoma cells in culture and on the growth of the tumor in nude mice. In nude mice with subrenally implanted U-87 MG glioblastomas, AGM-1470 significantly inhibited tumor growth (P < 0.01), and in nude mice with intracranial U-87 MG glioblastomas, AGM-1470 prolonged survival. In addition to its expected action as an angiogenesis inhibitor, AGM-1470 also directly inhibited U-87 MG cells in culture at concentrations similar to those that inhibited endothelial cells. The combined inhibition of glioblastoma cell mitosis and of glioblastoma-induced neovascularization suggests that AGM-1470 should be considered for further investigation in the treatment of this fatal tumor.
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PMID:AGM-1470 inhibits the growth of human glioblastoma cells in vitro and in vivo. 805 85

Glioblastoma, glioma or neuroblastoma cells were examined for the expression of IL-4 receptors (IL-4R) by flow cytometric analysis and 125I-IL-4 binding. These cancer cell lines expressed IL-4R which were of high affinity (KD = 700 x 10(-12) M) on glioblastoma cells. To investigate the function of these receptors and to target potent cytotoxic antitumor agents to human neurological cancers, we utilized IL4-PE4E, which is composed of IL-4 and mutant Pseudomonas exotoxin (IL4-PE4E). This chimeric molecule was cytotoxic toward human glioblastoma, neuroblastoma and glioma tumor cells in a dose-dependent manner. The cytotoxicity of IL4-PE4E was specific, since it was neutralized by excess IL-4, and by an anti-IL-4 monoclonal antibody in all types of brain tumor tested. IL2-PE4E and IL6-PE4E were not cytotoxic, nor was an IL4-PE4E mutant lacking ADP-ribosylating activity, indicating the IL4-PE4E-mediated cytotoxicity of the brain tumor cells required both IL-4R binding and enzymatic toxin activity. These data indicate that human neurological cancer cells express IL-4R which are targets for the cytotoxic effects of IL4-toxin. In addition, our data also suggest that IL4-PE4E should be studied further as a potential treatment for human neurological cancers.
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PMID:Human neurological cancer cells express interleukin-4 (IL-4) receptors which are targets for the toxic effects of IL4-Pseudomonas exotoxin chimeric protein. 805 54

In order to elucidate the role of inflammatory cytokines in the central nervous system, we examined the production of two leukocyte chemoattractants, IL-8 and monocyte chemotactic and activating factor (MCAF) in brain tumor cell lines. The glioma cell lines tested exhibited high levels of IL-8 and MCAF mRNA expression upon stimulation with IL-1 or TNF-alpha, while none of the neuroblastoma cell lines expressed these cytokine mRNA. Both IL-8 and MCAF mRNA expression depended on the dose of IL-1 alpha and TNF-alpha and appeared very rapidly, reaching maximal levels at 3-6 hr, with substantial production of these cytokines in the culture supernatants. When various immunosuppressive drugs were tested, glucocorticoids but not other immunosuppressive drugs markedly inhibited the IL-1 or TNF-alpha-induced IL-8 and MCAF mRNA accumulation, suggesting that glucocorticoid is a potent regulator of these inflammatory cytokine production in the neural tissues. In addition, reverse transcription-polymerase chain reaction (RT-PCR) revealed the expression of IL-8 and MCAF mRNA expression in resected brain tumor tissues including glioblastoma, astrocytoma grade 2, ependymoma and medulloblastoma, indicating that these inflammatory cytokines are expressed in vivo.
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PMID:Induction and regulation of IL-8 and MCAF production in human brain tumor cell lines and brain tumor tissues. 811 36

Nervous system-specific transcription factors that bind to the octameric deoxyribonucleic acid sequence motif ATGCAAAT (or ATTTGCAT) are known as N-Oct proteins. Neurons and glia contain the ubiquitous Oct-1 protein and four polypeptide complexes termed N-Oct-2, N-Oct-3, N-Oct-4, and N-Oct-5. Previously, we showed that N-Oct proteins are differentially expressed by human neuroblastoma and glioblastoma cell lines in vitro. We have now extended this work to freshly isolated human primary and metastatic brain tumors. Contrary to brain tumor cell lines, of the five astrocytomas and three glioblastomas analyzed, all but two tumors displayed the complete N-Oct protein profile, irrespective of histopathological tumor grade. Two astrocytomas were negative for N-Oct-4. Ten of 13 ependymomas exhibited N-Oct-2, N-Oct-3, and N-Oct-4 but lacked the N-Oct-5 complex. In contrast, brain metastases of two patients with extracerebral carcinomas contained only Oct-1, and cerebral metastases from two cases of B cell lymphomas showed Oct-1 and Oct-2 complexes, the characteristic Oct protein pattern of B lymphocytes. Thus, metastatic carcinoma and lymphoma expressed a non-nervous system phenotype of Oct proteins.
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PMID:Primary brain tumors differ in their expression of octamer deoxyribonucleic acid-binding transcription factors from long-term cultured glioma cell lines. 812 49

Considerable interest in the roles of serine proteases and serine protease inhibitors (serpins) in regulating physiologic and pathologic tissue remodeling has led to studies that indicate their critical participation in development and diseases of the brain. Plasminogen activator inhibitor-1 (PAI-1) is the most significant regulator of fibrinolysis in plasma, but little is known of the levels or activities of this important serpin in normal brain and brain tumors. For this reason, we estimated qualitative and quantitative levels of PAI-1 in normal human brain and various brain tumors. Western-blot results indicated that a 51 kDa band recognized with polyclonal anti-PAI-1 was more prominently in metastatic and glioblastoma than in meningiomas and low-grade gliomas; normal human brain lacked any detectable band. Reverse zymography also showed high levels of PAI-1 in malignant brain tumors. The complex formation with 125I-urokinase demonstrated that PAI-1 complex levels were increased in metastatic and glioblastoma when compared with low-grade gliomas and meningiomas. Since PAI-1 acts as a modulator of fibrinolysis, a better understanding of the balance between serine proteases and PAI-1 is likely to enhance our knowledge of brain tumor biology.
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PMID:Increased levels of plasminogen activator inhibitor-1 (PAI-1) in human brain tumors. 816 58


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