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)

Malignant glioma cells secrete transforming growth factor-beta (TGF-beta) which has potent immunosuppressive properties. We investigated the effect of interleukin-1 beta (IL-1 beta) on TGF-beta secretion from malignant glioma cells in vitro. T98G glioblastoma cells were treated with various doses of IL-1 beta and the TGF-beta activity in the supernatant was determined using a specific bioassay. Six other human malignant glioma cell lines were also treated with 1000 U/ml of IL-1 beta, and the TGF-beta activity in the supernatants was determined. The effect of IL-1 beta on the growth of tumor cells was also assessed by a bioassay using crystal violet which reflects the actual cell number in the plate wells. IL-1 beta treatment resulted in inhibition of TGF-beta secretion in two malignant glioma cell lines. TGF-beta secretion from T98G cells was suppressed by IL-1 beta in a dose-related manner. However, IL-1 beta treatment resulted in an obvious increase (> 20%) of TGF-beta secretion in two tumor lines, and a slight increase (< 20%) in three tumor lines. IL-1 beta did not affect the growth of four malignant glioma cell lines, and only slightly affected the growth of the other three cell lines. IL-1 beta modulates TGF-beta secretion from malignant glioma cells, but not in a consistent way.
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PMID:Modulation of transforming growth factor-beta secretion from malignant glioma cells by interleukin-1 beta. 886 49

Malignant glioma (glioblastoma and anaplastic astrocytoma) remain incurable despite extensive resection, radiotherapy, chemotherapy and experimental therapies. Few studies have addressed either the costs of various treatments for malignant glioma or their cost effectiveness. The aims of this study were to identify direct hospital costs of treating patients with biopsy proven malignant glioma. The study was carried out within the setting of a dedicated neuro-oncology clinic at a university teaching hospital and included 236 patients treated between 1989 and 1995. The study used the unit costing of each item of treatment according to NHS National Costing Project. The cost of treatment was broken down into its various components: bed days, investigations, surgery, radiotherapy, chemotherapy and neuro-oncology out-patient follow-ups. The mean costs for each of the items based on 1995 figures for the 157 patients having surgery followed by radiotherapy were neuroradiological investigations (442 Pounds), neurosurgical bed days (2407 Pounds), neurosurgery (2068 Pounds), neuropathology (434 Pounds), radiotherapy (8832 Pounds), out-patients (1078 Pounds) and chemotherapy (440 Pounds). Total treatment costs per patient ranged from 1978 Pounds to 26,980 Pounds. Median costs of care decreased sequentially with worsening MRC Brain Tumour prognostic group. Management of patients with the best prognosis (MRC index score of 1-10) cost a median of 16,550 Pounds (range 4572-26,090 Pounds) whilst the median management cost of those in the worst prognostic group (MRC score 34-38) was 6514 Pounds (range 1978-18,360 Pounds). The median cost of each week of survival in the patients with the best outcome (MRC score 1-10) was < 150 Pounds compared to 232 Pounds for each week of survival for patients in the worst prognostic group (MRC score 34-38). This study made no attempt to collect costs of supportive or community-based care. Prospective studies are required to collect such data, as well as assessing the costs effectiveness of alternative treatment strategies.
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PMID:The costs of managing patients with malignant glioma at a neuro-oncology clinic. 1101 62

Malignant glioma in adults and primitive neuroectodermal tumors/medulloblastomas in children are the most common malignant primary brain tumors that either respond poorly to current treatment or tend to recur. Adoptive therapy with TALL-104 cells-an IL-2-dependent, major histocompatibility complex nonrestricted, cytotoxic T-cell line-has demonstrated significant antitumor activity against a broad range of implanted or spontaneously arising tumors. This study investigates distribution of systemically and locally administered TALL-104 cells and their efficacy in effecting survival of a rat model of human brain tumor. In vitro, TALL-104 cells showed significant cytotoxic activity when added to human glioblastoma cell lines U-87 MG, U-251 MG, and A1690; the medulloblastoma cell lines DAOY, D283 Med, and D341 Med; and the epidermoid cancer cell line A431. In brain tumor-bearing rats, the amount of fluorescent dye-labeled TALL-104 cells in brain increased after they were given by intracarotid injection as compared with i.v. cell administration. However, TALL-104 cells rapidly decreased to low levels within 1 h after intracarotid injection. This finding suggests that TALL-104 cells given systemically may not invade brain or tumor tissues, but rather may remain in the vascular system, making this approach less efficient for brain tumor treatment. In a model of athymic rats engrafted with human A431 carcinoma brain tumor, repetitive local administration of TALL-104 cells directly into the tumor bed resulted in a significant increase in survival time compared with control animals. Therefore, local therapy with TALL-104 cells may be a novel and highly effective treatment approach for malignant brain tumors.
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PMID:Antitumor activity of a human cytotoxic T-cell line (TALL-104) in brain tumor xenografts. 1130 19

Alterations in the expression of growth factors and their receptors are associated with the growth and development of human tumors. One such growth factor is IGF-I (insulin-like growth factor I ), a 70-amino-acid polypeptide expressed in many tissues, including brain. IGF-I is also expressed at high levels in some nervous system-derived tumors, especially in glioblastoma. When using IGF-I as a diagnostic marker, 17 different tumors are considered as expressing the IGF-I gene. Malignant glioma, the most common human brain cancer, is usually fatal. Average survival is less than one year. Our strategy of gene therapy for the treatment of gliomas and other solid tumors is based on: 1) diagnostic using IGF-I gene expression as a differential marker, and 2) application of "triple-helix anti-IGF-I" therapy. In the latter approach, tumor cells are transfected with a vector, which encodes an oligoribonucleotide--an RNA strand containing oligopurine sequence which might be capable of forming a triple helix with an oligopurine and/or oligopyrimidine sequence of the promotor of IGF-I gene (RNA-IGF-I DNA triple helix). Human tumor cells transfected in vitro become down-regulated in the production of IGF-I and present immunogenic (MHC-I and B7 expression) and apoptotic characteristics. Similar results were obtained when IGF-I antisense strategy was applied. In both strategies the transfected cells reimplanted in vivo lose tumorigenicity and elicit tumor specific immunity which leads to elimination of established tumors.
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PMID:IGF-I: from diagnostic to triple-helix gene therapy of solid tumors. 1254 4

Frequent loss of heterozygosity (LOH) and mutations of the tumor suppressor gene PTEN (phosphatase and tensin homologue deleted from chromosome 10) have been found in sporadic gliomas. The most documented regions of allelic losses include 9p21, 10q23-25 and 17p1 3 whereas PTEN aberrations are preferentially found in glioblastoma multiformes. This research aimed to detect the incidence of allelic losses on chromosomes 10q, 9p, 17p and 13q and mutations on exons 5, 6 and 8 of PTEN in malignant gliomas. Malignant glioma specimens obtained were classified histopathologically according to the WHO criteria. Each tumor was then subjected to polymerase chain reaction (PCR)-LOH analysis using microsatellite markers and single-stranded conformational polymorphism (SSCP) analysis. Twelve of 23 (52%) malignant glioma cases showed allelic losses whereas 7 of 23 (30%) samples showed aberrant band patterns and mutations of PTEN. Four of these cases showed LOH in 10q23 and mutations of PTEN. The data on LOH indicated the involvement of different genes in the genesis of glioma whereas mutations of PTEN indicated the role of PTEN tumor suppressor gene in the progression of glioma in Malay population.
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PMID:Malignant glioma: the involvement of loss of allelic heterozygosity and PTEN mutations in a group of Malay patients. 1612 50

Invasion of tumor cells into the surrounding normal brain tissues is a prominent feature of malignant gliomas. Malignant glioma cells secrete thrombospondin-1 which participates in the motility of glioma cells and binds cell surface heparan sulfate proteoglycan. To clarify the invasion mechanism of tumor cells, expression of the syndecans (syndecan-1, -2, -3, and -4), a major cell surface heparan sulfate proteoglycan family, was analyzed in malignant gliomas. Involvement of nuclear factor-kappaB (NF-kappaB) on syndecan-1 expression was also investigated. Using reverse transcription-PCR, the authors analyzed the expression of syndecan-1, -2, -3, and -4 in 10 malignant glioma cell lines, 2 glioblastoma specimens, and 2 normal brain specimens. All malignant glioma cell lines and glioblastoma specimens expressed all types of syndecan mRNA, except in one glioma cell line that lacked syndecan-3 expression. On the other hand, normal brain specimens expressed syndecan-2, -3, and -4 mRNA, but did not syndecan-1 mRNA. Syndecan-1 protein was localized in the cell surface of all malignant glioma cell lines by flow cytometry. Various levels of active nuclear factor-kappa B (NF-kappaB) was detected in all malignant glioma cell lines using immunoblotting. The expression of active NF-kappaB and syndecan-1 increased in U251 glioma cells after tumor necrosis factor-alpha or interleukin-1beta treatment, which can activate NF-kappaB. The amplification of active NF-kappaB and syndecan-1 by tumor necrosis factor-alpha or interleukin-1beta was suppressed by an inhibitor of NF-kappaB activation (emodin). Emodin also downregulated the expression of syndecan-1 mRNA in U251 cells. These results indicate that malignant glioma cells express all types of syndecans and suggest that NF-kappaB participates in the upregulation of the syndecan-1 expression at the transcriptional level, and increased expression of syndecan-1 could associate with extracellular matrices including thrombospondin-1.
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PMID:Expression of syndecans, a heparan sulfate proteoglycan, in malignant gliomas: participation of nuclear factor-kappaB in upregulation of syndecan-1 expression. 1613 27

The current chemotherapeutic treatment of glioblastoma patients has minor success. Little is known about the molecular and cellular mechanisms of the resistance of gliomas towards current therapies. This study investigated both suppressive cellular effects and regulation of extracellular matrix remodeling proteins with pro-invasive activity in surviving human glioblastoma cells under clinically relevant treatments. All cellular and molecular biological investigations were performed on the genetically well-defined and clinically relevant p53-wild type U87Mg glioma cells. Malignant glioma cells underwent either radiation or temozolomide treatments alone, or combined chemo/radio treatment. Protein expression patterns were investigated by two-dimensional polyacrylamide gel electrophoresis followed by protein spot identification using tandem mass spectrometry analysis. Specific expression levels were quantified by Western-blotting. Extracellular gelatinase activities for both metalloproteinases MMP-2 and MMP-9 were determined by zymogramms. Survival curves indicated no effective suppression of glioma cells under all treatment conditions tested. Morphological changes demonstrated sub-lethal effect of both temozolomide and combined treatment. Expression of MMP-2, MMP-9, and membrane type 1 matrix metalloproteinases (MT1-MMP) was differentially up-regulated by increasing cellular density and treatment conditions. A significantly enhanced extracellular degrading activity under all treatment conditions tested was demonstrated for MMP-2 only. Being a marker for brain tumour progression and angiogenesis, lysozyme c was highly up-regulated under the combined chemo/radio treatment. The activation of proteins with pro-invasive activity indicates an increasing malignancy grade of surviving glioma cells under treatment conditions tested correlating well with more aggressive tumour phenotypes observed clinically in recurrences of treated glioblastomas.
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PMID:Pro-invasive gene regulating effect of irradiation and combined temozolomide-radiation treatment on surviving human malignant glioma cells. 1680 66

Malignant glioma is the most commonly occurring primary malignant brain tumor. It is difficult to treat and is usually associated with an inexorable, rapidly fatal clinical course. Chemotherapy, radiotherapy, and surgical excision are core components in the management of malignant glioma. However, chemotherapy, even with the most active regimens currently available, achieves only modest improvement in overall survival. Novel agents and new approaches to therapy are required to improve clinical outcomes. Irinotecan, a first-line treatment for metastatic colorectal cancer and an agent with high activity against solid tumors of the gastrointestinal tract, is an inhibitor of topoisomerase I, a critical enzyme needed for DNA transcription. Irinotecan crosses the blood-brain barrier and, in preclinical investigations, has demonstrated cytotoxic activity against central nervous system tumor xenografts. Its antitumor activity has also been demonstrated against glioblastoma cells with multidrug resistance. Studies in adult and pediatric patients with recurrent, intractable malignant glioma have evaluated irinotecan as monotherapy and in combination with other agents, including temozolomide, carmustine, thalidomide, and bevacizumab. Studies of irinotecan in combination with other medications, particularly temozolomide and bevacizumab, have yielded promising results. Irinotecan monotherapy has demonstrated efficacy; however, its efficacy appears to be enhanced when used in combination with other chemotherapeutic agents. When administered concurrently with enzyme-inducing antiepileptic drugs, the dosage must be increased to compensate for enhanced cytochrome CY3A4/5 enzyme activity. Toxicities associated with irinotecan have been manageable; the most important dose-limiting toxicities are neutropenia and diarrhea. Irinotecan-based chemotherapy of malignant glioma merits further study.
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PMID:Experience with irinotecan for the treatment of malignant glioma. 1878 79

Malignant glioma is resistant to the induction of apoptosis, resulting in a subsequent failure of chemotherapy in clinical treatment strategies. Downregulation of bcl-2 and bcl-xl expression in glioblastoma cells can induce apoptosis. BH3-only proteins, which include Bmf, are essential initiators of stress-induced cell death and apoptosis. Whether PS-341 regulates expression of BH3-only proteins in glioblastoma cells during the procedure of apoptosis is unclear. This study was designed to investigate the effects of PS-341 on glioma cell death and its possible signaling pathway. Our results demonstrate that Bmf is upregulated by PS-341 in A172 and T98G cells, and Bmf has a crucial role in PS-341-mediated cell death. In addition, we found that expression of Bmf is regulated by JNK phosphorylation.
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PMID:Bmf is upregulated by PS-341-mediated cell death of glioma cells through JNK phosphorylation. 1926 18

Malignant glioma (MG) is highly proliferative and invasive, with the malignant characteristics associated with aneuploidy and chromosomal instability (CIN). Here, we found that the level of germinal center-associated nuclear protein (GANP), a mammalian homologue of yeast Sac3, was markedly decreased in MGs with a poor prognosis; and thus we explored the effect of its decrease on cell-cycle progression of MG cell lines. Glioblastomas showed a significantly lower level of ganp mRNA than anaplastic astrocytomas, as measured by real-time reverse transcription-PCR, in 101 cases of adult MG. MGs of ganp(Low) expression displayed more malignant characteristics, with loss of heterozygosity on chromosome 10, epidermal growth factor receptor gene amplification, and significantly poorer prognosis than the ganp(High) group. Human diploid fibroblasts depleted of ganp mRNA by the RNA interference (RNAi) method showed a decreased percentage of S-phase cells and a cellular-senescence phenotype. MG cell lines harboring abnormalities of various cell-cycle checkpoint molecules displayed slippage of mitotic checkpoints and an increased proportion of hyperploid cells after ganp RNAi-treatment. These results suggest that GANP protects cells from cellular senescence caused by DNA damage and that a significant decrease in GANP expression leads to malignancy by generating hyperploidy and CIN.
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PMID:Decreased expression of germinal center-associated nuclear protein is involved in chromosomal instability in malignant gliomas. 1968 85


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