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)

In order to establish the standard of administration of ACNU against brain tumors, pharmacokinetic analysis of ACNU in tumor tissue, cystic fluid, cerebrospinal fluid and blood was performed. The sample specimens were obtained sequentially after intravenous administration of 1--2 mg/kg/BW of ACNU and quantitatively analysed by high-performance liquid chromatography in 3 cases of glioblastoma and each one case of astrocytoma, meningioma and brain metastasis. Concentrations of ACNU in blood was calculated by two compartment open model and those in cystic fluid was calculated by one compartment model using BMDP-3R program. The half-time in blood was 2.6--4.1 min, and its distribution was very fast. The penetration of ACNU into the tumor tissue was sufficient, because the central compartment was 23% and the tissue compartment was 77%. The transmission rate constant into the cyst was 1.8 and the elimination rate constant was 0.96. The maximum concentration in the cystic fluid 42 min after intravenous injection of 2 mg/kg/BW of ACNU was 0.27--0. 35 mg/dl. In conclusion, 3--4 mg/kg/BW of ACNU should be injected intravenously at one time.
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PMID:[Pharmacokinetic analysis of ACNU in brain tumors (author's transl)]. 52 72

The effect of recombinant human interleukin 1 beta (rHuIL-1 beta) on myelosuppression induced by 3-[(4-amino-2-methyl-5-pyrimidynyl)methyl]-1-(2-chloroethyl)-1-nit rosourea hydrochloride (ACNU) was studied. In in vivo study using BALB/c mice, pretreatment with 1 microgram/mouse of rHuIL-1 beta as a single intraperitoneal (i.p.) injection had a significant preventive effect on thrombocytopenia as well as granulocytopenia induced by ACNU at an intravenous dose of 60 mg/kg. Facilitated recovery by rHuIL-1 beta administered seven days after injection of high-dose ACNU was also observed. Experimental combination immunochemotherapy with high-dose ACNU and rHuIL-1 beta was performed in nude mice inoculated with human glioblastoma subcutaneously. The elongation of the survival time of the tumor bearing nude mice was also observed in combined use of high dose ACNU with rHuIL-1 beta. Seven patients with malignant brain tumors received intravenous 2.5-3 mg/kg ACNU. All patients were subcutaneously injected with 2 x 10(4)-U or more rHuIL-1 beta twice a week or daily. The mean nadir of leukocyte, granulocyte, and thrombocyte counts of the 7 patients received 2.5-3 mg/kg ACNU were significantly higher than in matched historical controls. In combination with rHuIL-1 beta, it may be possible to use chemotherapeutic agents at a relatively high dose.
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PMID:Preventive effects of interleukin 1 beta for ACNU-induced myelosuppression in malignant brain tumors: the experimental and preliminary clinical studies. 133 50

In order to evaluate a possible significance of the expression of proliferating cell nuclear antigen (PCNA) as clinically useful prognostic parameter, we retrospectively investigated a series of 40 glioblastomas by means of immunohistochemistry and compared the results to patient survival. All glioblastomas included in the study had been treated by operation, radiotherapy and intraarterial ACNU [3-(4-amino-2-methyl-5-pyrimidinylmethyl)-1-(2-chloroethyl)-1-nitr osourea] chemotherapy. Patient survival ranged from 2 months to 42 months (mean: 14.2 months). PCNA values varied widely, ranging from 0.5% to 75% (mean: 24.9%). Statistical analysis revealed no significant correlation between PCNA index and patient survival. Our study thus indicates that the expression of PCNA appears not to be a useful prognostic parameter for glioblastoma patients.
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PMID:Immunohistochemical demonstration of proliferating cell nuclear antigen in glioblastomas: pronounced heterogeneity and lack of prognostic significance. 137 10

Northern blot analysis with O6-methylguanine-DNA methyltransferase (MGMT) cDNA as a probe was used to analyze the MGMT activity regulating drug resistance of human cells to chloroethylnitrosoureas (CENUs). By this method, the expression levels of MGMT mRNA in six human glioma cell lines and 12 human brain tumor tissues from surgical specimens were determined. These MGMT mRNA levels were compared with the SD10 values of the tumor cells, estimated by cell survival assay, which indicated their resistance to the anticancer drug, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU). Human brain tumors that were highly resistant to ACNU, such as glioblastoma Gbl1 and metastatic brain tumor Col1 with SD10 values (microM) of above 100, expressed markedly increased amounts of 0.95 kb MGMT mRNA. In contrast, tumor cells such as U-87MG, U-251MG, U-343MG, U-373MG and SF-126 with SD10 values of under 14 indicating low resistance to ACNU scarcely synthesized any MGMT mRNA. These results indicated that the level of expression of MGMT mRNA in human brain tumors determined by Northern blot analysis truly reflects their cellular resistance to ACNU. Thus the Northern method with MGMT cDNA probe reported here is a practical and reliable method for estimation of cellular resistance to CENUs such as ACNU and for screening the chemotherapeutic response to CENUs of human brain tumors.
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PMID:Expression of O6-methylguanine-DNA methyltransferase and chloroethylnitrosourea resistance of human brain tumors. 151 62

The combined effects of x-irradiation and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloro-ethyl)-3-nitrosourea (ACNU) on multicellular glioblastoma A-7 spheroids were analyzed by means of cell survival and dose-response curves. The actual dose-response curve for small spheroids was almost identical to that estimated from the cell survival curve. It was strongly suggested that a small number of radiation-resistant cells, which were not detected in the cell survival curve, were present in large spheroids with central necrosis. The enhancing effect of ACNU was greater with large spheroids than with monolayer cells or small spheroids. A possible explanation for this is that ACNU is higher effective against the few radiation-resistant cells that may be present in larger spheroids.
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PMID:Effects of X-irradiation alone and in combination with ACNU on human glioblastoma cells in vitro. 169 44

A novel antitumor antibiotic, 11-acetyl-8-carbamoyloxymethyl-4-formyl-14-oxa-1, 11-diazatetracyclo [7.4.1.0(2,7).0(10,12] tetradeca-2,4,6-trien-6,9-diyl diacetate, FK973, was obtained as a fermentation product from Streptomyces sandaensis. This drug showed excellent cytotoxic effects on human glioblastoma and medulloblastoma and murine glioma (203 glioma) cells. The antitumor effects were also observed in ACNU-resistant glioma cells. The median survival time (MST) of MG models was 15 days. When they were treated with FK973, their MST was prolonged to 21 days. FK973 showed no apparent damage to murine brain cells.
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PMID:Cytotoxic effects of a new antitumor antibiotic, FK973, in malignant glioma. 177 43

The cooperative study on the beta-interferon (IFN) therapy for glioblastoma and malignant astrocytoma reported the response rate as 14.0%. Continuing study resulted the response rate of 24.0% to low grade astrocytoma and 20.0% to medulloblastoma. Totally, effectiveness of 19.2% to gliomas was confirmed in 120 evaluated cases. A randomized study was conducted on combination therapy with beta-interferon and chemoradiotherapy. The response rate of 41.2% (21/51) in the group treated with IFN, ACNU and Radiation was significantly higher than the rate of 19.6% (10/51) in the group treated with ACNU and radiation only. Application of IFN to a maintenance therapy is also on going. Adoptive immunotherapy has been developed as potential therapeutic method of malignant glioma. Lymphokine activated killer cells (LAK) and Tumor infiltrating lymphocytes (TIL) are put to clinical use. Clinical application of human monoclonal antibody (MAb) CLN-IgG was conducted to recurrent malignant glioma. 131I labeled MAb was administered intratumorously and the specific incorporation was confirmed by gamma-scintigraphy. Concomitant administration of interferon enhanced the efficacy of the therapy. This radio-immunotherapy holds future promise as a new therapeutic approach to gliomas.
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PMID:[Advances of BRM therapy of malignant brain tumors]. 199 12

The therapeutic potential of interleukin 1 (IL-1) in the treatment of malignant glioma was investigated. The direct effect of recombinant human IL-1 beta (rHuIL-1 beta) on cultured U-373 MG glioma cell was evaluated in vitro by BrdU uptake assay, and these effects were compared with those of human interferon beta (HuIFN-beta). Though a growth inhibition and an increase of the percentage of process bearing cells were observed with rHuIL-1 beta at a concentration of 100 ng/ml, these in vitro effects of rHuIL-1 beta were less than those of HuIFN-beta at the same concentrations. Prevention of and enhanced recovery from myelosuppression caused by ACNU by rHuIL-1 beta were evaluated in BALB/c mice. Intravenous injection of ACNU at a dose of 60 mg/kg caused marked decreases in the number of leukocytes, neutrophils, reticulocytes and thrombocytes after seven days. Pretreatment with 1 microgram/mouse of rHuIL-1 beta as a single i.p. injection had a significant preventive effect on these myelosuppression including thrombocytopenia. Enhanced recovery by rHuIL-1 beta administrated seven days after injection of ACNU was also observed. Experimental combination immunochemotherapy with ACNU and rHuIL-1 beta was performed in nude mice inoculated with human glioblastoma subcutaneously. More than 60 mg/kg of ACNU given intraperitoneally inhibited the growth of human glioblastoma in nude mice, but had no effect on survival time of nude mice. The antitumor effect of ACNU was significantly augmented by coadministration of 1 microgram/mouse rHuIL-1 beta. The elongation of the survival time of the tumor bearing nude mice was also observed in combined use of ACNU with rHuIL-1 beta. These results suggest that the combined use of IL-1 with chemotherapeutic agents seems to be desirable for clinical application in the treatment of patient with malignant gliomas from the viewpoints of the direct anti-tumor effect, the enhancement of the host immunity, and the prevention of myelosuppression caused by those agents.
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PMID:[Application of interleukin 1 in the treatment of malignant gliomas with special reference to the experimental combination therapy with ACNU]. 235 Jan 91

Human glioblastoma A-7 (GB A-7) cells can apparently recover from potentially lethal X-irradiation. The authors, using a colony-forming assay, studied the influence of pretreatment with 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) on the effectiveness of X-irradiation against GB A-7 cells grown in monolayers and as multicellular spheroids. Pre-exposure to ACNU inhibited the recovery of irradiated GB A-7 cells. In monolayer cells, the combination treatment was most effective when ACNU was applied 2 to 8 hours prior to irradiation, and the larger the X-ray dose, the more potent the effect. ACNU pretreatment was more effective against large spheroids (enhancement ratio 1.86) than against small ones (1.34). Large spheroids showed necrosis, whereas small ones did not. Isobolographic analysis disclosed that the effect of combining X-irradiation and ACNU is within an additive envelope at the surviving fraction of 10(-2), while supra-additive at the surviving fraction of 10(-3). These results suggest that the potency of X-irradiation is augmented by ACNU pretreatment through an interactive mechanism. Further, suppression of recovery from X-ray induced potentially lethal damage was influenced by the presence of necrosis.
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PMID:[Enhancement of the effect of X-irradiation against cultured human glioblastoma cells by pretreatment with ACNU]. 248 84

Twelve cases of malignant gliomas (anaplastic astrocytoma 4, glioblastoma 8, recurrent 3, primary 9) were treated with ACNU and radiation with sensitizing agents after the surgical removal of the tumor. BUdR, Vidarabine (Ara-A), Aciclovir (ACV) were applied for sensitizing agents. BUdR was administrated intraarterially prior to radiation (380 rad, two times a week), and Ara-A and ACV intravenously during and after the radiation. Total dosage of the radiation was 50-60 Grey for each case. All recurrent and eight primary patients died. The mean survival time of the recurrent patients was 17.7 months, while that of the primary patients was 13.4 months. One of the primary patient was glioblastoma and is still surviving more than 24 months by now. The complete response (CR) rate of the primary tumor patients observed by computerized tomography (CT) scan was 5/9. We can expect the availability of this trial for malignant gliomas because of high CR rate in primary tumor cases.
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PMID:[A trial of ACNU and radiation therapy with sensitizing agents for malignant gliomas]. 262 8


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