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)

We studied the non-major histocompatibility-restricted cytotoxic activity induced by interleukin 2 (IL-2) and interferon alpha (IFN-alpha) in mononuclear cells of peripheral blood (PBMNC) from glioblastoma patients. We observed a depressed cytotoxic activity against natural killer (NK)-sensitive target cells in PBMNC from all the patients studied. Culture of these PBMNC with IFN-alpha for 5 days augmented the cytotoxic activity against NK-sensitive target cells in a small group of patients. Incubation with IL-2 for 5 days normalizes the decreased cytotoxic activity against NK-sensitive target cells of PBMNC from all the glioblastoma patients studied. When PBMNC from these patients were incubated with IL-2 for 5 days and IFN-alpha was added to the culture medium in the last 2 h of culture, an enhancement of non-major histocompatibility-restricted cytotoxic activity was observed compared with that obtained with either IL-2 or IFN-alpha alone. This improvement of the cytotoxic activity was more relevant when it was tested against NK-resistant target cells. The potential utility of the sequential use of the two cytokines in generating non-major histocompatibility cytotoxic activity in glioblastoma patients is discussed.
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PMID:Interleukin 2 and interferon alpha modulation of the lymphocyte non-major histocompatibility-restricted lytic activity in glioblastoma patients. 146 64

The induction of human immunodeficiency virus type 1 (HIV-1) gene expression by cytokines was investigated in cells of central nervous system origin. These were human neuroblastoma, glioblastoma, and astrocytoma cell lines, a murine oligodendroglioma and primary murine astrocyte cultures. The cytokines used were tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), IL-6, and interferons alpha and gamma (IFN alpha, gamma). Transient transfection of cells with a chloramphenicol acetyltransferase (CAT) reporter gene under the control of the HIV-1 long terminal repeat (LTR) showed significant augmentation following treatment by particular cytokines. TNF alpha was found to augment HIV LTR-directed CAT activity in all cell types. IL-1 beta also activated the HIV LTR reporter gene in glioblastoma, astrocytoma, and astrocyte cells. IL-6 enhanced HIV gene expression in one example only, the primary astrocyte cultures. The interferons generally suppressed expression from the LTR except IFN gamma which produced a twofold rise in the murine glial cells and IFN alpha augmenting expression in one neuroblastoma cell line. No synergy was observed between pairs of activating cytokines tested. The HIV tat gene product was found to be functional in all cells, cotransfection of a tat expression vector transactivating expression from the LTR, with varying degrees of efficiency. In some cell lines the combination of an activating cytokine and tat resulted in an enhancement above that obtained by cotransfection of tat alone. In others, the level of CAT activity did not significantly change. Analysis of nuclear extracts from cytokine-treated cells further implicated the involvement of NFKB in the induction of HIV-1 gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine augmentation of HIV-1 LTR-driven gene expression in neural cells. 159 55

It is known that natural killer (NK) cells are involved in immunosurveillance against tumours. This study examines the NK activity of mononuclear cells (MNC) from the peripheral blood of patients with glioblastoma. The cytotoxic inducer effect of interferon-alpha (IFN-alpha) upon these MNC has also been studied. A marked decrease in NK activity mediated by MNC from these patients was found. This functional defected in MNC is not due to a decrease in phenotypically defined NK cells. After long-term (5-day) incubation with IFN-alpha, MNC from 5 out of 14 patients showed strong lytic activity against NK-sensitive target cells. In this system, IFN-alpha failed to induce cytotoxic activity against NK-resistant target cells in MNC from all the patients studied. This in vitro induction of cytotoxic activity in MNC from some patients with glioblastoma by IFN-alpha suggests a potential immunotherapeutic use of the lymphokine in these subjects.
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PMID:Modulation by interferon alpha of the decreased natural killer activity in patients with glioblastoma. 185 28

Interferon-gamma (IFN-gamma) regulates a variety of immunoregulatory functions through the induction of a specific set of IFN-gamma response genes. This includes the invariant chain associated with the major histocompatibility complex class II molecules. To investigate the mechanism involved in the invariant chain (In) response to IFN-gamma we constructed chloramphenicol acetyltransferase (CAT) hybrid genes in which the CAT gene is under the control of the In promoter. The glioblastoma cell line, U-373 MG, transfected with a CAT construct having the In promoter sequence -790 to +1 bp showed over 3-fold increased CAT activity when treated with IFN-gamma indicating that this region confers IFN-gamma responsiveness to the CAT gene. The IFN-gamma response element in the promoter was further sublocalized to the region -120 to -61 base pairs (bp). This region contains homology to the interferon-stimulated response elements identified in other IFN responsive genes. By gel shift analyses, an IFN-gamma-induced sequence-specific DNA-binding factor was identified. This induced complex binds to an oligonucleotide corresponding to -107 to -79 bp of the In promoter. Mutations of this binding site at -94 and -92 bp drastically decreased binding of the constitutive and IFN-gamma-induced complexes. This IFN-gamma induced factor also binds to an oligonucleotide corresponding to -91 to -62 bp of the interferon-beta (IFN-beta) gene promoter, a region necessary for the induction of the IFN-beta gene by virus and double-stranded RNA. This binding specificity is characteristic of a family of DNA binding factors that bind both the interferon-stimulated response elements and the IFN-beta gene promoter.
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PMID:Interferon-gamma-inducible regulation of the human invariant chain gene. 189 64

To study the regulation of major histocompatibility complex class II antigen by central nervous system cells, the expression of one of these antigens, human leukocyte antigenDR (HLADR) in three human glioblastoma cell lines (HTB14, 16 and 17) and a neuroblastoma cell line (HTB11) was determined. Interferon-gamma (IFN gamma) induced HTB16 and HTB17 cells to express HLADR, and enhanced the antigen expression in HTB14 cells, but it failed to induce HLADR expression in HTB11 cells. Tumor necrosis factor-alpha amplified and accelerated the expression of HLADR induced by IFN gamma in HTB16 cells. Interleukin-1 beta, prostaglandin E2 and transforming growth factor-beta suppressed IFN gamma-induced HLADR expression in HTB16 cells. Several other substances tested did not affect HLADR expression or IFN gamma-induced HLADR. These findings confirm that IFN gamma plays a role in the regulation of HLADR expression in cells derived from the brain and that some other cytokines modify IFN gamma-HLADR interactions.
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PMID:Modulation of human leukocyte antigenDR expression in glioblastoma cells by interferon gamma and other cytokines. 195 63

The combined effects of Acyclovir [9-(2'-hydroxyethoxymethyl)guanine; ACV] and human interferon-alpha (IFN-alpha) on replication of the herpes simplex virus type I (HSV-1) were determined in human neural cell lines, neuroblastoma (IMR), glioblastoma (118MGC), and glioma (U251MG). HSV-1 grew well in all these cells, with final yields of more than 1 x 10(6) PFU/ml. In terms of virus-yield reduction, ACV was found to be highly effective in IMR, moderately effective in U251MG, but ineffective in 118MGC. By contrast, IFN-alpha reduced the virus yield significantly in 118MGC and in U251MG, but did not in IMR. Combined application of ACV and IFN-alpha strongly inhibited the virus replication in all three cell lines with various degrees of synergism or additive effect. These results were also confirmed by immunofluorescent examinations. The sensitivity of HSV-1 to ACV or IFN-alpha was found to be different among the three different cell types. By combining the two agents, the virus growth was strongly suppressed in all the cells. These results suggest the importance of combination therapy for severe type of herpes simplex encephalitis in clinical practice.
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PMID:Combined effects of acyclovir and human interferon-alpha on herpes simplex virus replication in cultured neural cells. 255 47

In order to clarify the mechanism of action of recombinant human leucocyte interferon, the effect of local injection of it to the human malignant gliomas (one oligodendroglioma, the other glioblastoma) transplanted into nude mice were evaluated. The volume of the tumors were calculated as 1/2 (short diameter [cm])2 x (long diameter[cm]). And the ratio of tumor volume (T)/original size (C) were calculated in terms of experimental day. Among the groups of control (vehicle of IFN injected), 1 million units of IFN locally injected group, 3 million units injected group, and 9 million units injected group, the effects of the treatment were statistically evaluated in terms of T/C. At the end of the experiment, each animal was injected 4 mg of BrdU intraperitoneally, and the labeling indices of the tumor tissue were measured and compared among the groups above mentioned. Local injection of IFN to the tumor was effective even at the dose of 1 million units every other day for 16 days for glioblastoma and 50 days for oligodendroglioma. The labeling index of the treated groups was significantly reduced when compared to that of control group in both tumors. And the experiment was performed to evaluate the variation of NK activity and ADCC activity of mouse spleen cells among the experimental groups. For the oligodendroglioma, NK activities were significantly increased in the 9 million units of IFN injected group when compared to those of control group. For glioblastoma, there was no definite variation of NK and ADCC activities among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effect of local injection of interferon against human malignant glioma transplanted into nude mice and the mechanism of its effect]. 259 May 60

The growth inhibitory effects of the combination of beta-interferon (beta-IFN) and conventional anticancer drugs such as adriamycin (ADM) and ACNU were evaluated in nude mice receiving subcutaneous transplants of human glioblastoma. Next, the anticancer and radiation sensitizing effects of beta-IFN on human glioblastoma was also evaluated in nude mice model. After three weeks of combined treatment, tumour reduction rates (treated/control values) were evaluated by the Battelle's method. In conclusion, the growth inhibitory effect of IFN was most enhanced when IFN was administered following radiotherapy. Furthermore, the combined effect was enhanced in proportion to the dose of radiation.
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PMID:Interactions of human fibroblast interferon with chemotherapeutic agents and radiation against human gliomas in nude mice. 287 8

We show that human glioblastoma cells, moving from exponential growth into a state of density-dependent growth arrest, demonstrate a 7-fold drop in the total number of alpha-IFN-receptors expressed per cell. This loss of receptor activity was not seen when cells were grown in the presence of anti-alpha-IFN-monoclonal antibody. The active binding sites expressed on the arrested cell population were of reduced affinity for IFN, relative to the high-affinity sites expressed on the growing cells, resulting in a 3-fold lower initial rate of IFN-binding to the arrested cells. We exploited this difference to investigate the relationship between IFN receptor binding and induced gene transcription. As determined by nuclear run-off assays, the transcriptional response of both the gene family 1-8 and 2-5A synthetase to IFN treatment also showed a 3-fold reduction in density-arrested cells. Longer-term (0-8 h) induction and down-regulation of gene transcription in IFN-treated cells closely followed the binding to, and down-regulation of, cell surface-localized IFN receptors. Furthermore, inhibition of the intracellular breakdown of IFN did not affect transcriptional responses to IFN. Thus transcription of these IFN-induced genes is closely linked to surface receptor occupancy and is most likely mediated by transmembrane signals alone.
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PMID:Transcriptional regulation of interferon-responsive genes is closely linked to interferon receptor occupancy. 301 7

The effects of human lymphoblastoid interferon-alpha (MOR-22) on the growth of xenografted human tumors in nude mice were examined. IFN-alpha was administered subcutaneously to mice with renal tumor (ACHN), intratumorally for glioblastoma (U-373MG) or intravenously with uterine cervical tumor (HeLa S3). The dosages of IFN-alpha were 2 X 10(4)-5 X 10(5) IU/mouse for ACHN tumor, 1 X 10(5)-5 X 10(5) IU/mouse for U-373MG tumor and 3 X 10(4)-1 X 10(5) IU/mouse for HeLa S3 tumor. IFN-alpha inhibited the growth of these tumors in a dose-dependent manner.
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PMID:[Study on human lymphoblastoid interferon-alpha (MOR-22): Part III. Antitumor effect on nude mouse-transplanted human tumors]. 375 41


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