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)

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 effects of hyperthermia and antineoplastic agents on the cytotoxicity to normally oxygenated and chronically hypoxic glioma cells were investigated in vitro. Exposure to temperatures above 43.0 degrees C was less cytotoxic to hypoxic cells which predominantly accumulated in the G0/G1 phase fraction. On the other hand, mitomycin C (MMC) and adriamycin (ADM) were preferentially cytotoxic to hypoxic cells not only at 37 degrees C but also at elevated temperatures (42 degrees C and 43 degrees C). These two agents showed marked synergistic effects with hyperthermia under both oxygenated and hypoxic conditions. In contrast, bleomycin (BLM), cis-diamminedichloroplatinum(II) (CDDP), and vincristine (VCR) were preferentially cytotoxic to oxygenated cells at both 37 degrees C and elevated temperatures. CDDP showed cytotoxic synergism with hyperthermia that appeared to be oxygen-dependent. A nitrosourea derivative, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), showed no major preferential toxicity under either oxygenated or hypoxic conditions. This study suggests that hyperthermia in combination with MMC or ADM would have a greater cytotoxic effect on hypoxic cell subpopulations of malignant gliomas.
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PMID:Effects of antineoplastic agents and hyperthermia on cytotoxicity toward chronically hypoxic glioma cells. 154 59

Cell lines resistant to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3- (2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) show a high degree of collateral sensitivity to L-asparaginase. The mechanism for this phenomenon was investigated by comparing the nutritional requirements and asparagine synthetase activity of the resistant sublines to those of parent cells. Nine ACNU-resistant sublines were isolated from rat glioma 9L cells after incubation with various concentrations of ACNU in Ham's F-12 medium. The 9L cells grew independently of asparagine, developing well in asparagine-deficient Dulbecco's modified Eagle's medium. In contrast, the growth rates of all nine ACNU-resistant sublines decreased under the same conditions and required the addition of 10(-4) M asparagine for maximum growth. Asparagine synthetase activity in the ACNU-resistant cells was much lower than in the 9L cells, suggesting that the requirement for asparagine in the resistant sublines was due to reduced activity of this enzyme. A growth-inhibition assay showed that the ACNU-resistant sublines were more sensitive to L-asparaginase than 9L cells by up to 2 x 10(5)-fold. These results suggest that L-asparaginase therapy has the potential to become a new approach for treating acquired ACNU resistance.
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PMID:Hypersensitivity of rat glioma sublines with acquired ACNU resistance to L-asparaginase. 168 27

In treating brain tumors with chemotherapy, the choice of drug is most important since human tumors have different drug sensitivities and growth rates. We have been studying the therapeutic effect of anticancer drugs against malignant brain tumors in the following in vivo models. 1) Human glioma-bearing nude mice. 2) Methylcholantrene-induced 203Gl mouse glioma-bearing immunocompetent C57BL/6 mice. 3) Human gliomas transplanted into the chorioallantoic membrane of chick embryos. We evaluated the advantages of each model for anti-cancer drug sensitivity tests. 1) Human glioma-bearing nude mice were found to be most useful in predicting the direct effects of anticancer drugs. We evaluated the effects of several drugs such as ACNU or interferons in six glioma strains transplanted into nude mice. 2) Immunocompetent C57BL/6 mice models were found useful in predicting the therapeutic effects of biological response modifiers. In this model, we can also evaluate changes in immunological parameters such as NK activities or T cell subsets. 3) In the drug sensitivity test using the CAM of chick embryos, various kinds of gliomas could be grafted with a high rate of success. The tumor reduction rate of the sensitivity test using this system tended to agree with that using nude mice. This test was found to be useful in predicting the effect of drugs against gliomas directly resected from individual patients.
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PMID:[Drug sensitivity test against malignant gliomas]. 169 88

Since 1984, we have treated 11 malignant glioma patients with intracarotid infusion of ACNU [1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)- 3-nitrosourea hydrochloride] in addition to surgical removal and irradiation. We experienced three patients, who showed clinical manifestation of leukoencephalopathy and computed tomographic (CT) findings of diffuse low-density areas in the white matter on the side of ACNU infusion. Two of the three patients showed an additional CT finding of ring enhancement in the temporo-occipital region. The histological diagnosis of the first case was radiation necrosis, while that of the others was recurrent tumor with coagulation necrosis in the surrounding brain. Our experience suggests that intracarotid ACNU infusion increases the hazard of radiation necrosis, and the optimum dose and effective mode of administration should be evaluated.
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PMID:Diffuse low-density areas in white matter on CT scans after intracarotid ACNU infusion--report of three cases. 170 59

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

The authors report malignant glioma occurring in two sibling cases. The elder brother presented with right hemiparesis and hemihypesthesia at 14-year-old. Computed tomographic (CT) scanning demonstrated a low-density area in the left frontoparietal lobe. The tumor was partially removed. Histologic diagnosis was glioblastoma multiforme. Radiation therapy was given postoperatively, but he died due to tumor recurrence 15 months after onset. The younger sister was admitted comatose due to intratumoral bleeding at 19-year-old. CT scans showed a high-density area in the right temporal lobe. The tumor was excised subtotally. Histological diagnosis was malignant astrocytoma (grade III). Radiation therapy, chemotherapy (ACNU), and immunotherapy (interferon) were given postoperatively, but she died due to recurrence 34 months after onset.
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PMID:Siblings with malignant glioma--report of two cases. 171 48

Various modes of administration of ACNU (nimustine hydrochloride) were tried to make clear which mode is the best method to obtain intrathecal diffuse distribution of ACNU to match the condition of killing of glioma cells (10 micrograms/ml; greater than 30 min.). Tried modes of administration included 1)bolus injection into ventricular cavity, 2)bolus injection into cisterna magna, 3)bolus injection into lumbar subarachnoid space, 4)ventriculo-lumbar perfusion, 5)chiasmatic cistern-lumbar perfusion. Used dose of ACNU was 5 mg/body for all modes of administration. ACNU level in CSF was measured by HPLC method specially developed by authors. To make clear intrathecal distribution of ACNU, autoradiography using 14C-ethylene-ACNU was studied after administration of 10 muCi/Kg of radioactive ACNU. The images were studied by image analyzer system (BAS-2,000 system developed by Fuji Film Co. Ltd). Among the modes of administration tried, ventriculo-lumbar perfusion method gave the best results in terms of lumbar, ventricular, cisterna magna, and basal cistern distribution of ACNU to match the cell kill condition experimentally ascertained. Although, bolus injection of ACNU into cisterna magna gave sufficient amount of ACNU in lumbar region, the initial level of ACNU was too high in cisterna magna, and administration of ACNU once a week for three times in a canine cisterna magna resulted in considerable deterioration of brain stem and basal structure. In addition to it, the level of ACNU in ventricular cavity was not detectable. Lumbar bolus injection resulted in also too much ACNU accumulation at the injected lumbar area, and at the cisterna magna region, ACNU was not detectable.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Intrathecal distribution of ACNU by various modes of its administration analyzed by HPLC and autoradiography]. 174 91

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

Three ACNU-resistant sublines (R1, R3 and R12) from rat glioma 9L cells showed cross-resistance to vinblastine, adriamycin, and VP-16. Among these, the R3 subline also acquired radioresistance under aerobic conditions. Total glutathione levels in these sublines were elevated 2- to 3-fold. Treatment of the cells with BSO, a specific inhibitor of GSH synthesis, resulted in decreased intracellular total glutathione levels in all 4 cell lines to about 10% of control levels. However, sensitivity to radiation or to chemicals did not change accordingly. Treatment of 9L cells with OTZ, a precursor of cysteine, resulted in a rise in intracellular GSH levels but it did not correlate with sensitivity to X-ray or to ACNU. These results suggest that, in terms of cellular sensitivity to radiation or ACNU, total glutathione level alone cannot serve as a predictive indicator.
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PMID:Glutathione and cellular response of ACNU-resistant rat glioma sublines to drugs and radiation. 186 Jul 33


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