Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytotoxicity of human beta-interferon (HuIFN-beta) produced in human glioma cells was examined by use of our liposomes entrapping two plasmids, pSV2neo and pSVMTV-IFN-beta. After the cells had been transfected with these genes by means of the liposomes, neomycin-resistant cells were selected. When the selected cells were subjected to a single exposure to dexamethasone, all of the cells were found to produce HuIFN-beta and were eliminated by 8 days. Accordingly, the effect of HuIFN-beta produced in human glioma cells is considered to be cytocidal.
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PMID:Cytotoxicity of human beta-interferon produced in human glioma cells transfected with its gene by means of liposomes. 129 Apr 60

We have employed IAR therapy [combination of postirradiation, chemotherapy and interferon (IFN)] for malignant glioma patients. Changes of lymphocyte fractions in patients were evaluated before and after IAR therapy, using a recently developed two-color analysis. Eight malignant glioma patients received irradiation, chemotherapy (ACNU) and immunotherapy (OK-432 and IFN-beta). Peripheral blood lymphocytes taken during hospitalization with IAR therapy (first half and latter half), and every 3 to 6 months for 2 years at the longest after IAR therapy were double-stained with FITC- and PI-labelled antibodies and two-color analysis was conducted by a FACS Analyzer. Six patients out of 8 survived for 6 months to 2 years, 2 died after 3 and 6 months, respectively. Leu-2a (suppressor/cytotoxic T), especially Leu-2a+ 15- (cytotoxic T) showed a high value. Leu-2a level decreased during treatment, and both Leu-2a+ 15- and Leu-2a+ 15+ (suppressor T) values decreased. Two thirds of the patients showing an increased Leu-2a+ 15+ level died. Leu 3a (helper/inducer T), especially Leu-3a+ 8+ (inducer T) level decreased, but Leu-3a+ 8- (helper T) level increased during treatment. The level decreased in the worse patients. Leu-3a/Leu-2a ratio was low, but it increased during treatment as compared with the results of conventional therapy. Leu-7, Leu-11a, NK activity, and gamma-IFN productivity were further studied. Treatment combined with IFN revealed an influence on the T cells resulting in an increase of helper T level and suppression of suppressor T level.
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PMID:[Multidisciplinary therapy using interferon and immunological evaluation for glioma patients: two-color analysis of T cell subsets]. 170 57

A multicenter phase I-II trial of intravenous (IV) human recombinant interferon beta (rIFN-beta; Betaseron; Triton Bioscience Inc, Almeda, CA) was conducted in children with recurrent or progressive primary brain and spinal cord tumors. A total of 29 patients were enrolled: high-grade astrocytoma (12), brainstem glioma (nine), and primitive neuroectadermal tumor (three), ependymoma (two), germ cell (two), and spinal cord astrocytoma (one). Betaseron was given by IV infusion over 30 minutes 3 times per week (Monday-Wednesday-Friday [MWF]). Four dose levels were studied, and at least three patients were entered at each dose level. The treatment plan began with a three-step dose escalation for each patient over 6 weeks (initiation phase). The dose-escalation schema for the four dose levels was: 50-100-200, 100-200-400, 200-300-500, and 300-400-600 x 10(6) (M) IU/m2. Patients experiencing an objective response or stable disease after 6 weeks entered the maintenance phase at the final escalated dose, ie, 200, 400, 500, or 600 mlU/m2 (MWF). Common transient effects included chills, fever, and fatigue. Dose-limiting toxicities were hematologic, hepatic, and CNS. The maintenance maximum-tolerable dose (MTD) was 500 mlU/m2, ie, dose level 3. Response was assessed at completion of the initiation phase and at 2-month intervals during the maintenance phase. Objective partial responses were seen in patients with high-grade astrocytoma (two) and brain-stem glioma (two). Thus, four of 21 (19%) assessable patients had partial responses for a median of 4 months. Eight patients had stable disease for a median of 5+ (2 to 14+) months. Antineoplastic activity has been identified in children with high-grade astrocytomas and brainstem gliomas in a dose-intensive regimen.
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PMID:Recombinant interferon beta: a phase I-II trial in children with recurrent brain tumors. 201 20

The distribution of 125I-labelled recombinant mouse interferon-beta (rMuIFN-beta) in normal and glioma (203 glioma) bearing mice was studied by radioassay and macro-autoradiography at 15 and 30 min after a single intravenous injection. The level of rMuIFN-beta in the spleen was about 20-fold higher than in serum. Concentrations higher than the serum level was detected in the lung, liver and kidney. The concentration of rMuIFN-beta in the brain was 8% of the serum level and the concentration in the glioma 30 min after administration was about 10-fold higher than in normal mouse brain. Macro-autoradiographic study demonstrated a wide distribution range and selective uptake in glioma tissue. Furthermore, we found that mouse gliomas were sensitive to mouse IFN-beta. Our findings demonstrate that in the mouse glioma model, intravenously administered interferon reaches the tumour.
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PMID:Distribution of mouse interferon-beta in normal and brain tumour-bearing mice. 206 66

Recombinant interferon beta (IFN-beta ser) has been administered by intravenous bolus injection three times weekly at a dose of 90 x 10(6) IU to 14 patients with recurrent malignant glioma in an ongoing study. The treatment period has ranged from 1 to 40 weeks. The most common adverse experiences were fever, chills, malaise, and headache. Fever, chills and headache were worse with the first two doses and were usually relieved with acetaminophen. All patients tolerated subsequent treatments without any difficulties. No neurologic or hematologic toxicities were observed. Of ten evaluable patients, five had progressive disease in 4 to 8 weeks; three had stable disease for 12 to 21 weeks; one has had a minor response for 13 weeks; and one has had a complete resolution of tumor for 150 + weeks. IFN-beta ser appears to have activity in human glioma and is well tolerated at this dosage and schedule.
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PMID:A pilot study of recombinant interferon beta (IFN-beta ser) in patients with recurrent glioma. 208 58

The antiproliferative effects of human recombinant interferon-alpha (rIFN-alpha A) and interferon-beta (rIFN-beta ser) were assessed in vitro against seven human glioma cell lines. Further analysis of one of these lines (EFC-2) in response to rIFN-alpha A demonstrated a minimum growth inhibition by day 6 of treatment, whereas a 50% inhibition of cell growth was observed with a dose of 50 U/ml of IFN-beta ser. No significant growth inhibition was seen by rIFN-alpha A at doses up to 500 U/ml. Addition of rIFN-alpha A to rIFN-beta ser-treated EFC-2 cells neither suppressed nor augmented the antiproliferative response to IFN-beta ser. The binding of 125I-labeled rIFN-alpha A or 125I-labeled rIFN-beta ser to EFC-2 cells was inhibited competitively by increasing concentrations of either unlabeled rIFN-alpha A or rIFN-beta ser. This suggests that the cellular receptors for both rIFN-alpha A and rIFN-beta ser appear to be intact and appear to bind both agents equally. Furthermore, incubation of EFC-2 cells for 72 h with either rIFN-alpha A or rIFN-beta ser resulted in an increase in 2',5'-oligoadenylate (2-5A) synthetase activity 5-fold with rIFN-alpha A and 50-fold with rIFN-beta ser. Similarly, the 68-kD IFN-induced protein kinase was induced substantially with rIFN-beta ser but only slightly induced with rIFN-alpha A treatment. These results suggest that EFC-2 human glioma cells demonstrate a differential sensitivity in terms of growth inhibition to rIFN-beta ser and to rIFN-alpha A which appears to correlate with a differential induction of both intracellular 2-5A synthetase and protein kinase activity. These results cannot be explained solely on the basis of surface receptor binding of rIFN-alpha A and rIFN-beta ser. These data do suggest that, for human glioma cells in culture, type I IFN receptors may display a subtle architectural variation that allows equivalent binding of both IFN-alpha and IFN-beta ser, but allows an enhanced signal transduction and biological effect only after binding a specific IFN subtype.
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PMID:Growth inhibitory effects of interferon-beta but not interferon-alpha on human glioma cells: correlation of receptor binding, 2',5'-oligoadenylate synthetase and protein kinase activity. 214 Mar 95

The antiproliferative effects of human interferons (IFNs) and double-stranded RNAs (dsRNAs) were studied in five human glioma cell lines. Dose response curves were generated over a 72 hour treatment period. The concentration of interferon or double-stranded RNA necessary to produce a 50% antiproliferative response (GI50) was calculated by linear regression analysis. Two cell lines were more sensitive to IFN-beta than to IFN-alpha, one cell line was more sensitive to IFN-alpha than to IFN-beta and two cell lines had approximately equal sensitivities to both interferons. All cell lines showed some sensitivity to either IFN-alpha or IFN-beta. IFN-gamma had no antiproliferative effect on any of the cell lines. In addition, only one of the cell lines displayed sensitivity to dsRNA, in which the response to poly(I).poly(C) was greater than that to a mismatched analogue of poly(I).poly(C), r(I)n.r(C12,U)n (Ampligen). There was no correlation between the sensitivities to type I IFNs (alpha and beta), type II IFN (gamma) or the dsRNAs. The antiproliferative effect of combinations of IFNs, or IFNs and Ampligen, was studied in one of the cell lines. A significant synergistic antitumor effect was seen with all of the IFN/Ampligen combinations (p less than 0.02), including IFN-gamma/Ampligen, even though these cells were resistant to IFN-gamma alone. Synergy was also seen in the IFN-alpha/IFN-gamma (p less than 0.02) and IFN-beta/IFN-gamma (p less than 0.05) combinations. The IFN-alpha/IFN-beta combination gave an additive antitumor effect. These results indicate that IFN-alpha and IFN-beta alone or combinations of type I IFNs, type II IFNs and Ampligen can be effective in inhibiting the growth of glioma cells.
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PMID:Sensitivities of human glioma cell lines to interferons and double-stranded RNAs individually and in synergistic combinations. 245 Jan 81

Sixteen patients with malignant glioma were treated by the intravenous administration of beta-interferon together with chemoradiotherapy. Five of the cases were recurrent gliomas. Seven of the 11 fresh cases were treated with beta-interferon, more than two months after cessation of the radiotherapy. Of the 16 cases, 12 cases showed partial regression of tumors, or no regrowth of tumors on CT scan, 2 cases showed no improvement, and 2 cases were unevaluable due to the short follow-up periods. IFN-beta is often administered, in combination with antineoplastic agents and radiotherapy, to patients with malignant glioma. Some patients have shown sufficient suppression of the growth of the malignant glioma only through administration of IFN-beta 1 x 10(6) IU once or twice a week. Some patients, however, have developed severe bone marrow suppression due to the combination therapy of IFN-beta and antineoplastic agents. Therefore, the blood of patients should be tested twice a week, and the data should be analyzed within the same day to determine the subsequent treatment. IFN-beta administration should be stopped if the platelet count drops below 1.0 x 10(5)/mm3 or half of the initial figure, and the course of disease of the patient should be carefully observed.
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PMID:[Efficacy and adverse effects of beta-interferon in the treatment of malignant glioma]. 261 79

Human TNF was detected fairly recently and at present the anti-tumor activity of human recombinant TNF is being examined against various malignant tumors of human origin. In the present study, we report the anti-tumor activity of recombinant human TNF against human malignant glioma cell lines in vitro and in vivo, in addition to its combined effects with HuIFN-beta. The in vitro study was conducted as follows. Thirteen human glioma cell lines were exposed to 100 U/ml TNF, 1,000 IU/ml HuIFN-beta, or both, and the suppression rate was calculated on days 3, 5 and 7. In the in vivo study, nude mice carrying a human glioma cell line, KMS II, in the subcutaneous tissues were divided into groups and drugs were administered intratumorally as described below. 1) control, 2) TNF 5,000 U single administration, 3) TNF 5,000 U, intermittently administered (once/week for two weeks), 4) TNF 5,000 U, continuously administered (3/week for two weeks), 5) HuIFN-beta 50 X 10(4) IU (3/week for two weeks), and 6) combination of 4) with 5). Results of the in vitro study revealed some suppressive effects on proliferation of tumor cells on day 7 in all 13 glioma cell lines examined with 100 U/ml TNF. And also, especially in 8 of 13 cell lines, the suppression rate was more than 30%. The suppressive effects of TNF were augmented by combined use of HuIFN-beta in all cell lines, giving a range of suppression of 67.8 to 99.3%. The in vivo study revealed that the mean tumor weight ratios (control = 100%) on day 19 (the end of the experiment) were as follows; single administration of TNF: 41.3%, intermittent: 46.7%, continuous: 26.7%, HuIFN-beta: 65.9%, combination: 18.5%. Statistical analysis disclosed significant suppressive effects on tumor proliferation between the control group and 3 TNF-administered groups (single, intermittent, and continuous) and that suppression in the continuously administered group was more severe in comparison with the group given single administration. Moreover, it was suggested that combination therapy with TNF and Hu IFN-beta was more effective than a single therapy with TNF only or HuIFN-beta only. From the results described above, it was found that human recombinant TNF had some cytotoxic effects against human malignant gliomas in vitro and in vivo, although the degree of cytotoxicity was not always higher in comparison with the effects of TNF.
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PMID:[Anti-tumor activity of human recombinant TNF against human malignant glioma cell lines and combined effect with Hu INF-beta]. 308 96

Treatment of partly purified large granular lymphocytes (LGL) with either IFN-alpha or IFN-gamma for 2 hr augmented their NK cell activity. This augmentation was completely inhibited by the addition of 10 micrograms/ml of cycloheximide. In contrast, when the effects of IFN-gamma on the synthesis of specific proteins in these cells was directly studied by use of two-dimensional gel electrophoresis, we found that IFN-gamma was unable to induce any of the earlier detected, IFN-alpha/IFN-beta-inducible proteins within 18 hr of incubation. No additional, IFN-gamma-induced proteins were detected in either the partly purified LGL or purified T cells. In contrast, the effects of the two factors were comparable in the glioma cell line 251 MG. This shows i) that the effects of IFN-alpha and IFN-gamma are dependent on the responder cell type, ii) that there exists at least one mechanism that can augment NK cell activity that is not dependent on the increased synthesis of the IFN-alpha-inducible proteins, and iii) that either the nine IFN-alpha-inducible proteins are not involved in any leukocyte function that is augmentable by both IFN-alpha and IFN-gamma, or that the two factors exert their actions in leukocyte through different mechanisms.
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PMID:The augmentation of human natural killer cell activity by interferon-gamma is not associated with the induction of the interferon-alpha-inducible proteins. 308 47


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