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)

Anti-tumor activities of ACNU and X-irradiation on methylcholanthrene induced glioma in C57BL mice were studied in vitro and in vivo. In vitro experiments using cultured glioma cells (MGB cells), the synchronization of cell cycle was done by excess addition of thymidine, and the anti-tumor cell effect were investigated by mean of determinations of DNA synthesis, mitotic index and the number of the living cells following the treatments. As the results, it appeared obvious that ACNU was most effective on MGB cells in S phase and X-irradiation in M phase. As to the combined therapy of ACNU and X-irradiation, the anti-tumor effect was most remarkable when the cells were treated by X-irradiation in the G2, M phase, which were hervested by addition of ACNU 44 hours before irradiation. However simultaneous treatment of ACNU and X-irradiation on the cells in G1 phase was not so remarkable. In vivo experiments the anti-tumor effect of ACNU and X-irradiation on subcutaneously or intracranially transplanted glioma in mice was investigated. Either ACNU 10 mg/kg or local X-irradiation 1240 rads showed inhibitory effect on the tumor growth and prolonged the survival time of the tumor bearing mice. The combination therapy was more effective than ACNU or X-irradiation alone, particularly combination therapy of ACNU and repeated small doses irradiation of X-ray was remarkably effective. Evidence obtained indicates that the combination therapy of ACNU and X-irradiation have synnergistic anti-tumor effect on experimental mouse glioma.
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PMID:[The anti-tumor effect of ACNU and X-irradiation on mouse glioma (author's transl)]. 50 42

Sixteen pediatric patients with brainstem glioma were treated with a combination of interferon-beta, 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitroso ure a hydrochloride (ACNU), and radiation therapy (IAR therapy). All patients received 1-1.5 million IU/day of interferon-beta intravenously for 1 week of each 6-week cycle. In addition, ACNU (2-3 mg/kg) was given on the 2nd day of each cycle. Conventional focal irradiation (1.5-2 Gy/day for 5 days to a total dosage of 40-60 Gy) was administered beginning on day 3. Patients underwent at least two 6-week cycles. Adverse effects included nausea, vomiting, and myelosuppression, but were mild and transient. Response to treatment was evaluated by the reduction in tumor size measured on postcontrast computed tomographic scans and magnetic resonance images. Responses occurred in 10 of 11 patients with the intrinsic type of brainstem glioma, including three complete and seven partial responses. Two of five patients with exophytic type gliomas partially responded. The median survival was 15.7 months, a remarkable improvement over the natural course of this disease. These results indicate that IAR therapy is a useful primary treatment for pediatric patients with brainstem gliomas.
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PMID:Effectiveness of interferon-beta, ACNU, and radiation therapy in pediatric patients with brainstem glioma. 128 18

A 35-year-old woman was admitted to our hospital with a 3 month history of progressive paraparesis and impairment of bowel and bladder function. MRI suggested a malignant glioma at the level of T9 to L1. Laminectomy and subtotal removal of the tumor was performed. The surgical specimen was a glioblastoma multiforme. An aggressive adjuvant therapy was scheduled to prevent rapid local regrowth and leptomeningeal dissemination. Radiotherapy with a total dose of 65Gy was delivered with chemotherapy including ACNU (2mg/kg) and vincristine (0.2mg/kg). Lymphokine-activated killer (LAK) cells were given intrathecally with a total dose of 1.6 x 10(9) LAK cells with 3 x 10(4) units of IL-2. MRI taken 6 months after surgery revealed no residual tumor, and no malignant cell was detected in the patient's CSF. After physiotherapy, she became able to walk with a stick and was discharged. Chemotherapy (ACNU 2mg/kg/8 weeks) had been further continued for 2 years. She did well until 14 months after surgery, when paraparesis recurred and rapidly progressed to completism. MRI revealed a spinal cord swelling with marked edema, suggesting delayed radiation necrosis. Two years after surgery, MRI showed a marked atrophy of the spinal cord, and no residual tumor. But 3 years after surgery, a round tumor at the level of T11 and T12 was revealed on MRI, and she was admitted to our hospital again. A spinal cord amputation was performed, and the tumor was totally removed without worsening her neurological symptoms. Surgical specimen of the tumor was glioblastoma multiforme again.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of spinal cord glioblastoma multiforme]. 131 Aug 3

The prognosis of malignant glioma is extremely poor. We applied conventionally fractionated irradiation combined with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), uneven fractionated irradiation with ACNU, low dose rate telecobalt therapy as a boost, and intraoperative irradiation against 110 malignant gliomas to investigate the efficacy of these methods as alternative treatments for malignant glioma. Although local tumor control by uneven fractionated irradiation was better than that by the other methods, no significant improvement was obtained in survival rates. As a result of multiple regression analysis, age and histology were major factors for survival rates, and the difference of treatment methods was not important. Both low-dose rate telecobalt therapy as a boost and intraoperative irradiation showed little advantage because of the high risk of brain necrosis associated with them.
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PMID:Treatment results by uneven fractionated irradiation, low-dose rate telecobalt therapy as a boost, and intraoperative irradiation for malignant glioma. 133 4

Intrathecal administration of ACNU ((1-4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitroso urea hydrochloride) had a remarkable chemotherapeutic effect in a rat model of meningeal gliomatosis. This effect was evaluated in rats with meningeal gliomatosis induced by an intracisternal inoculation of rat C6 glioma cells. The median survival time of the rats treated with a single dose of intrathecal ACNU (1 mg/kg) on Day 1 or Day 3 after tumor inoculation was significantly prolonged by 35.7% to 42.9% or 25.0% to 28.6%, respectively, as compared with that of the control animals. Meningeal gliomatosis rat models treated intrathecally with ACNU (1 mg/kg) 5 days after tumor inoculation or intravenously with ACNU (15 mg/kg) both failed to prolong the survival time of the animals. These findings suggest that intrathecal chemotherapy with a low dose of ACNU is effective in the early stages of meningeal gliomatosis, whereas intravenous chemotherapy with a high dose of ACNU is always ineffective.
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PMID:Intrathecal chemotherapy with ACNU in a meningeal gliomatosis rat model. 140 22

The antiestrogen drug tamoxifen, which is used extensively in the treatment of breast cancer, has also been reported to inhibit the proliferation of some estrogen receptor-negative cell lines, including malignant glioma in vitro. To explore the possible role of tamoxifen in the treatment of malignant glioma, we have investigated its effects on cell growth and radiosensitivity in C6 glioma cells using a colony-forming assay and a tetrazolium-formazan growth rate assay. Pretreatment of C6 cells with tamoxifen resulted in dose-dependent inhibition of cell growth and enhancement of the antitumor effects of ACNU and irradiation. The radiosensitivity of the treated cells was enhanced by the administration of 5 mumol/L of tamoxifen either before and during irradiation or continuously before, during, and after irradiation [37% survival dose (Do) = 2.68 +/- 0.19 and 2.64 +/- 0.04 Gy, respectively, P < 0.01)], as compared with controls (Do = 3.79 +/- 0.25 Gy). In addition, protein kinase C activity was also inhibited by tamoxifen at the concentration in which the radiosensitivity was augmented in C6 cells. Taken together, our results demonstrate a synergistic effect of tamoxifen with radiation on intracellular damage in C6 glioma cells, which may in part be due to the inhibition of protein kinase C, suggesting that tamoxifen serves as a useful agent in combination therapy of glioma.
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PMID:Enhancement of radiosensitivity by tamoxifen in C6 glioma cells. 140 59

ACNU [1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride], one of the chloroethylnitrosoureas (CENUs), is believed to be effective against malignant glioma when intravenously or intrathecally administered. A rat model with meningeal gliomatosis (MG) induced by an intracisternal inoculation of rat C6 or 9L glioma cells was intrathecally and intravenously treated with ACNU in order to test the feasibility of intrathecal chemotherapy with ACNU in the treatment of meningeal gliomatosis. The median survival time (MST) of the animals was significantly prolonged when ACNU was intrathecally administered at dosages of 0.5 to 1.5 mg kg-1 in the early stages of MG, i.e. within 3 days after the tumour inoculation, whereas intravenous therapy with ACNU at a dose of 15 mg kg-1 did not exhibit any efficacy in the rats inoculated with C6 glioma cells (C6-MG). Intrathecal ACNU, however, at dosages of up to 1.5 mg kg-1 failed to demonstrate any therapeutic effect in the late stage of MG, i.e. 5 days after the tumour inoculation, except in the rats inoculated with 9L brain tumour cells (9L-MG). Intravenous chemotherapy with ACNU at a dose of 15 mg kg-1 extended the MST of the 9L-MG rats more significantly in the late stage of MG than in its early stage. This points to the feasibility of intrathecal ACNU in the treatment of meningeal gliomatosis in its early stages, but not in its late stages in which intravenous ACNU might be more effective than intrathecal treatment against MG of which the parenchyma has already been deeply invaded by the tumour.
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PMID:Intrathecal chemotherapy with ACNU for meningeal gliomatosis. 145 69

To shed light on the metabolic changes in glioma following therapy, uptake changes among 18F-fluoro-2'-deoxyuridine (18FUdR), 14C-thymidine (dThd), 14C-methionine (Met) and 3H-deoxyglucose (DG) in glioma model after chemotherapy were studied, as a means for interpreting clinical PET results, together with the changes in the bromodeoxyuridine (BUdR) labeling index. 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(-2chloroethyl)-3-nitro sourea hydrochloride (ACNU) was administered intraperitoneally in the tumor-bearing rats and uptake of the tracers or BUdR labeling index in tumor tissue were measured. The metabolic response following chemotherapy was a sharp fall immediately for 14C-dThd and 18FUdR and a moderate fall for 14C-Met whereas there was a fall in 3H-DG from 1 week after chemotherapy. The changes of BUdR labeling index paralleled that in the uptake for dThd and FUdR. These result indicate that PET scans using a variety of tracers in conjunction could be used for clinical diagnosis and evaluation of therapy in glioma cases. 18FUdR is a promising tracer of nucleic acid metabolism to evaluate the proliferative potential of brain gliomas.
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PMID:Metabolic changes of glioma following chemotherapy: an experimental study using four PET tracers. 146 67

In a series of experiments on the combined use of radio- and chemotherapy for malignant glioma, X-rays combined with ACNU or 5-FU treatment caused a supra-additive effect on multicellular spheroids in vitro. In the present experiment, the effect of X-rays combined with 5-FU treatment on subcutaneously transplanted rat gliomas of RGC-6 cells was analyzed. The dose-survival curve for X-rays given to tumors in air-breathing rats was biphasic with a terminal slope (D0 = 4.3 Gy) that was parallel to that for tumors in previously killed rats. The hypoxic cell fraction thus obtained from the ratio of the surviving fraction in two parallel curves at 20 Gy was about 7% in the subcutaneous tumors in air-breathing rats. X-ray-induced, potentially lethal cellular damage recovered within 8 hours in these tumors. The surviving fraction of cells in the tumors decreased to a minimum at 4-6 hours after a 5-FU injection, but increased thereafter. A biphasic dose-response curve for 5-FU was also obtained for cells in these tumors, indicating the presence of 5-FU resistant cells. The effect of X-irradiation given at about 8 hours after a 5-FU injection was greater than the additive effect of both agents acting independently. This was true when an X-ray dose of more than 5 Gy was given.
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PMID:[Analysis on combined effect of X-rays with 5-FU on rat subcutaneous gliomas]. 150 45

A study was made of the membrane transport of cytoplasm and mitochondria stained fluorescence dye Rhodamine 6G (R6G). In rat glioma C6 cells and 1-(4-amino-2-methyl-5-pyrymidinyl)-methyl-3-(2-chloroethyl) -3-nitrosourea hydrochloride (ACNU) and vincristine (VCR) resistant cell lines (C6/ACNU, C6/VCR), the rate of uptake of R6G decreased in C6/VCR cells, but verapamil increased the intracellular accumulation of R6G in C6/VCR. The intracellular accumulation of R6G of C6/ACNU cells was essentially the same as that of wild-type cells. C6/ACNU cells did not show cross resistance and were sensitive to VCR and cisplatin. C6/VCR cells showed cross resistance to ACNU and CDDP, but C6/VCR cells in the presence of verapamil were more sensitive to drugs than C6/VCR cells in the absence of verapamil. We conclude that the reduction of R6G fluorescence staining intensity in C6/VCR cells compared to wild-type cells may be associated with the mechanism of multidrug resistance (MDR) but does not reflect the mechanism of resistance to ACNU. Verapamil increased the accumulation of R6G in C6/VCR cells and overcame MDR, suggesting that there is a correlation between the MDR overcoming effect and enhancement of R6G accumulation, and that this correlation validates the use of the R6G staining test for clinical and laboratory investigation of MDR.
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PMID:Fluorescent dye rhodamine 6G as a molecular probe to study drug resistance of C6 rat glioma cells. 151 98


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