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)

Antineoplaston (Ap), a new antitumor agent, was clinically tested for effects on malignant brain tumors. The materials were 3 cases of glioblastoma (G,B), 2 cases of anaplastic astrocytoma, 1 case of pontine glioma, 2 cases of metastatic brain tumor and 1 case of medulloblastoma. All patients underwent radiochemotherapy and surgical resection of the tumors except the cases of pontine glioma, metastatic brain tumor and anaplastic astrocytoma. For gliomas, radiochemotherapy was used with Hu-IFN-beta. Ap was administered at a dose of 7-10 g/day in combination with remission maintenance therapy of gliomas. Complete response was obtained in one anaplastic astrocytoma. Partial response was obtained in 2 cases, a pontine glioma and a metastatic brain tumor. No change was observed in 2 cases, an anaplastic astrocytoma and a multiple brain metastasis. Progression of the disease was observed in 4 cases, 3 glioblastomas and 1 medulloblastoma, which showed continuous increase in tumor size. The effects of Ap on malignant brain tumors were considered due to synergy, since it was administered with other drugs and acceleration of tumor cellular differentiation. Ap is useful as an approach to remission maintenance therapy for brain tumors.
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PMID:The effect of Antineoplaston, a new antitumor agent on malignant brain tumors. 747 50

To elucidate which cytokine receptors may be expressed by human glioblastoma and normal astrocytic cells, the presence of messenger ribonucleic acid (RNA) for a number of cytokine receptors was examined in 16 glioblastoma cell lines and adult and fetal astrocytes. A complementary deoxyribonucleic acid copy of total RNA was synthesized and amplified with specific primers using the polymerase chain reaction method. The receptors studied were interleukin (IL)-1 receptor type I (IL-1RI) and type II (IL-1RII), p75 and p55 tumor necrosis factor (TNF) receptors (p75TNFR and p55TNFR), interferon (IFN)-alpha/beta and -gamma receptors (IFN-alpha/beta R and IFN-gamma R), granulocyte-macrophage (GM) colony-stimulating factors receptor alpha subunit (GM-CSFR), G-CSF receptor (G-CSFR), M-CSF receptor (c-fms, M-CSFR), stem cell factor receptor (c-kit, SCFR), IL-6 receptor (IL-6R), and IL-8 receptor (IL-8R). Transcripts for IL-1RI, p55TNFR, IFN-alpha/beta R, and IFN-gamma R were present in all cell lines. The presence of IL-1RII, p75TNFR, GM-CSFR, M-CSFR, SCFR, IL-6R, and IL-8R was identified in 13, eight, seven, eight, 14, three, and one cell lines, respectively. Normal astrocytes were positive for IL-1RI, p75TNFR, p55TNFR, IFN-alpha/beta R, IFN-gamma R, M-CSFR, and SCFR, showing a similarity to glioblastoma cells. Expression of IL-1RII was observed in adult astrocytes but not in fetal astrocytes. Furthermore, gene expression was assessed in normal brain tissue and 11 glioblastoma tissue specimens. The normal brain tissue expressed IL-1RI, IL-1RII, IFN-alpha/beta R, M-CSFR, and SCFR. Of the 11 glioblastoma tissue specimens, IL-1RI was positive in 11, IL-1RII in 10, p75TNFR in nine, p55TNFR in nine, IFN-alpha/beta R in 10, IFN-gamma R in 10, GM-CSFR in two, G-CSFR in three, IL-8R in eight, and M-CSFR and SCFR in 11. These expressions were consistent with those in the cell lines, except for IL-8R. It is concluded that glioblastoma cells and normal astrocytes express a similar set of cytokine receptor genes in vitro and in vivo. Possible autocrine loops are suggested for IL-1 alpha/IL-1RI, TNF-alpha/p55TNFR, IFN-beta/IFN-alpha/beta R, M-CSF/M-CSFR, and SCF/SCFR in glioblastomas.
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PMID:Analysis of cytokine receptor messenger RNA expression in human glioblastoma cells and normal astrocytes by reverse-transcription polymerase chain reaction. 751 61

The inhibition by IFN-beta of acquired resistance to the epipodophillotoxin etoposide was studied using a human glioblastoma cell line, T98G. T98G cells were exposed to either etoposide alone or both etoposide and IFN-beta, and after subculture, the same two series of drug exposure were repeated. Degree of level of resistance was tested by the response of the cells to etoposide and changes in their DNA histograms. Furthermore, topoisomerase II in each set of cells was subjected to fluorescence staining with monoclonal anti-topoisomerase II antibody, and the amount of fluorescence was measured by flow cytometry. Secondary etoposide exposure showed less cytotoxicity when the first exposure was to etoposide alone. In contrast, the cytotoxicity was almost the same as that after the first exposure when IFN-beta was added. Resistance to etoposide may result from qualitative or quantitative alterations in the target enzyme, topoisomerase II. The present results show that resistant cells have less topoisomerase II than sensitive cells, suggesting that IFN-beta inhibits the acquisition of resistance to etoposide by suppressing the alteration in topoisomerase II. The inhibition of acquired resistance to etoposide by IFN-beta suggests that continuous and repeated chemotherapy for glioblastoma and other malignant tumors may be clinically advantageous.
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PMID:IFN-beta inhibition of etoposide resistance acquisition in vitro: studies using a human glioblastoma cell line. 776 95

There are three types of interferons (IFN), alpha, beta and gamma. IFN-alpha is produced in the leukocytes infected with virus, while IFN-beta is from fibroblasts infected with virus. IFN-gamma is induced by the stimulation of sensitized lymphocytes with antigen or non-sensitized lymphocytes with mitogens. It is believed that IFN-alpha and beta originated from the same ancestral gene, whereas IFN-gamma did not. IFN has not only an antiviral activity, but also various kinds of biological activities including cell growth inhibition, immunosuppressive effects, enhancement of macrophage, natural killer (NK) cell, killer (K) cell and neutrophil functions, and cell differentiation-inducing activity. IFN also shows the antitumor activity resulting from the integration of the above-mentioned biological activities. IFN is also deeply involved in the pathogenesis of various diseases, e.g., collagen diseases such as SLE and rheumatoid arthritis, insulin-dependent diabetes mellitus, fulminant hepatitis, severe pancreatitis, nephritis, multiple sclerosis, allergic diseases, and atherosclerosis. At present, IFN is clinically used in therapy against virus infections such as hepatitis B and C, and for malignancies such as renal cell carcinoma, multiple myeloma, malignant melanoma, glioblastoma, skin cancers, malignant lymphoma and chronic myelogenous leukemia.
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PMID:[Interferon-alpha, beta, gamma]. 799 28

IFN-gamma induces the production of N-formyl-kynurenine from L-tryptophan in various cell types by the induction of the enzyme indoleamine 2,3-dioxygenase (IDO). The IFN-gamma induced IDO activity in the glioblastoma cell line 86HG39 and cells of clone 2D9 derived from this cell line was found to be greater than that in Hela cells and U373MG cells. Consequently 2D9 cells were used in all subsequent experiments. The determination of kynurenine in the supernatant of IFN-gamma activated cells was performed photometrically using a microplate reader. It was found that the amount of kynurenine produced was directly proportional to the amount of IFN-gamma used to activate cells. The detection limit for IFN-gamma of this assay was 20 U/ml. The induction of L-tryptophan degradation was specific for IFN-gamma since neither IFN-alpha, IFN-beta, IL-1, IL-2, IL-6, GM-CSF nor TNF alpha induced the production of detectable amounts of kynurenine by 86HG39 and 2D9 cells. Furthermore, a mab directed against IFN-gamma was able to completely block the IFN-gamma induced IDO activation. This bioassay was used to determine the IFN-gamma content of supernatants harvested from toxoplasma antigen specific human T cell lines and clones. This assay gave reproducible results which correlated well with the IFN-gamma content detected in the same samples using a commercially available ELISA kit. Furthermore in the case of T cell supernatant stimulated 2D9 cells a mab directed against IFN-gamma was able to completely block IDO induction. We conclude that the measurement of kynurenine production induced by IFN-gamma can be used to determinate IFN-gamma content. This is a simple bioassay which can be performed with standard laboratory equipment.
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PMID:A new, simple, bioassay for human IFN-gamma. 828 93

Southern blot analyses of the 9p-localized type I interferon (IFN) genes in DNAs obtained from malignant glioma cell lines and glial tumor tissue have indicated that homozygous deletions of the IFN-alpha and IFN-beta genes often occur during the development of the highly malignant central nervous system neoplasm, glioblastoma. We have applied a set of markers that span the IFN region on 9p to the analysis of DNAs from 30 human glioma cell lines in order to define the region of homozygous deletion associated with this cancer more precisely. Fourteen of the cell lines revealed either complete (12 cases) or partial (2 cases) homozygous deletions of the IFN-alpha gene cluster; no instances of homozygous deletions were observed that did not involve the IFN-alpha region. Genomic DNA identified by the markers nearest to and flanking the IFN-alpha genes were retained in 5 of the cases with homozygous deletions. Consequently, these results limit the extent of homozygous deletions in glioma cell lines to a small region of 9p21-p22 that includes most of the type I IFN locus.
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PMID:Localization of chromosome 9p homozygous deletions in glioma cell lines with markers constituting a continuous linkage group. 833 74

As the prognosis of astrocytic tumors depends on various factors, identifying prognostic factors should be useful for developing strategies to cope with them. Between 1975 and 1994, more than 200 patients with astrocytic tumors were treated in Kagoshima University. Of these patients, 149 (grade I: 17, grade II: 42, grade III: 41, grade IV: 42, unproven: 7) have been followed up. Records of these patients were retrospectively reviewed for age at the time of initial symptoms, gender, histological grade (WHO), extent of tumor resection, radiation therapy, and administration of anticancer agents. We used the Kaplan-Meier method and the Weibull log-linear model to analyze the relation between survival time and these prognostic factors. Survival time was counted from onset of symptoms, and age of initial treatment was used as a covariant. The mean age of males at the initial diagnosis was 40.8 years (n = 77), and that of females was 39 years (n = 72). Using the Kaplan-Meier method, the mean survival time of the 149 patients was 101 months (males; 72.7 months, females; 134.5 months). Mean survival time of grade II was 144.3 months, that of grade III was 95.2 months, and grade IV (glioblastoma) was 15.9 months. Histological grades and mean ages of the groups showed a positive correlation. Among grades II, III and IV, the Kaplan-Meier survival curves were significantly different (p < 0.0001) according to the log-rank test. By the extent of surgical resection (subtotal or greater resection, partial resection, and less than partial resection), the mean survival time showed a significant difference (p < 0.05) on the log-rank test. However, we could not detect a significant difference in survival time between the group that received chemotherapy and the group which did not. The Weibull log-linear analysis indicated that gender, age, histological grade (WHO), extent of surgery, and dose of radiation therapy were prognostic factors. Covariants of grades II, III, and IV made survival time 0.314, 0.179, and 0.069 times as long as that of grade I. The survival time after "partial resection" became 1.415 times as long as the survival time after "less than partial resection". The covariant of "greater than subtotal resection" showed a prolonged survival time of 2.916 compared with that of "less than partial resection". As for age at treatment, the older the patient was, the shorter the survival time. The rate was 0.986 for each year of age. Irradiation of one Gy increased survival time by 1.015 times. Chemoimmunotherapy (dose of ACNU and interferon beta) could not be confirmed as an effective covariant.
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PMID:[The prognostic factors in astrocytic tumors: analysis by the Kaplan-Meier method and the Weibull log-linear model]. 882 30

In this study, we examined the clinical course and prognosis of 32 patients with malignant glioma (17 patients with anaplastic astrocytoma, 15 patients with glioblastoma) treated with the MIC regimen (radiation, MCNU, carboplatin and IFN-beta) or MICE regimen (radiation, MCNU, carboplatin, etoposide and IFN-beta). Ten patients were treated with the MIC regimen and 22 patients with the MICE regimen. The patients treated with the MIC and MICE regimens exhibited no significant difference in clinical background factors. The response rate was 50.0% among the 8 evaluable patients treated with the MIC regimen, and 40.0% among the 20 evaluable patients treated with the MICE regimen. The first- and second-year survival rates for the MIC regimen were 40.0% and 30.0%, and those for the MICE regimen were 68.2% and 36.4%. The overall first- and second-year survivals were 59.4% and 33.9%, respectively. The 50% survival time was 8.6 months for the MIC regimen, 14.9 months for the MICE regimen, and 13.4 months overall. There was no significant difference in response rate or survival period between the group treated with the MIC regimen and that treated with the MICE regimen. Age, histological grade of malignancy, radicality of surgery and total dose of irradiation did not affect length of survival. The only factors significantly related to length of survival were response to the induction therapy and performance of maintenance therapy. These results did not demonstrate the superiority of either the MIC or MICE regimen to other regimens previously reported for the treatment of glioma. In addition, etoposide was found not to improve the efficacy of this type of combined chemoradiation therapy.
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PMID:[A clinical evaluation of combination therapy with radiation, MCNU, carboplatin and IFN-beta or with radiation, MCNU, carboplatin, etoposide and IFN-beta for malignant gliomas]. 983 7

A 58-year-old man had been treated with one intravenous injection of 120 mg of nimustine hydrochloride (ACNU), ten thrice-weekly doses of 3,000,000 U of interferon beta, and brain irradiation for cerebral glioblastoma. One month later he had fever, appetite loss, a productive cough and dyspnea. Chest radiography and CT showed diffuse, nonsegmental ground glass opacity in both lung fields. Hypoxemia and lung shadows were exacerbated day by day. Bronchoalveolar lavage revealed an increases in the total cell count and the percentages of lymphocytes and neutrophils, and a decrease of the CD 4/8 ratio. Interferon beta therapy was stopped, and steroid pulse therapy and prednisolone 40 mg administration were initiated. The symptoms, hypoxemia and lung shadows quickly improved. Reported cases of interferon beta-induced pneumonia are rare.
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PMID:[A case of interferon beta-induced pneumonia]. 1110 6

In order to analyse immune-stimulatory effects of infection of human tumor cells with Newcastle Disease Virus (NDV), gamma-irradiated human breast carcinoma, colon-carcinoma or glioblastoma cells from defined cell lines were modified either by true infection with live virus or by cell surface adsorption of UV-inactivated replication deficient virus. Modification with live but not inactive NDV induced in all human tumor cells IFN-beta and the chemokines RANTES and IFN-gamma-inducible protein-10 (IP-10). In addition, infection by live NDV induced upregulation of HLA-ABC-molecules in all tumor lines tested and HLA-DR molecules in breast carcinoma lines. Two cell adhesion molecules, ICAM-I (CD54) and LFA-3 (CD58), were also upregulated on human tumor cells after infection with live NDV. When infection of MCF-7 breast carcinoma cells by NDV was performed in the presence of neutralizing anti-IFN-beta antibodies no upregulation of HLA molecules was observed suggesting an important role of IFN-beta in this process. Forty-eight to 72 hours after infection of the irradiated tumor cells with live NDV, many tumor cells were dead or in early or late stages of apoptosis. These results provide explanations for the function of the virus-modified autologous tumor vaccine ATV-NDV with which promising clinical results have already been obtained.
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PMID:Human tumor cell infection by Newcastle Disease Virus leads to upregulation of HLA and cell adhesion molecules and to induction of interferons, chemokines and finally apoptosis. 1206 54


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