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)

Rat gliomas of subcutaneously transplanted RGc-6 cells were irradiated with X-ray either alone, or combined with ACNU, and the cell-survival was assayed in vitro. Cell-survival curve composed of two components by X-irradiation alone indicated the presence of a hypoxic cell fraction. We have previously shown that combined treatment with ACNU apparently made the effect of X-ray on spheroids in vitro of the same cell line of RGc-6 more powerful. Although treatment of rat gliomas with ACNU administered at 2 hrs prior to X-irradiation was most effective, it resulted in only the additive effect of the independent action of the two agents. Further treatment by O6-ethylguanine prior to ACNU administration and X-irradiation apparently increased the strength of the effect of ACNU combined with X-ray to the dose-modifying factor for X-ray of 1.8. The result indicated that the combination of O6-ethylguanine prior to ACNU administration and X-irradiation may clinically enhance the effect of X-ray against apparent ACNU-resistant glioma cells such as RGc-6 cells.
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PMID:[Effect of X-rays combined with ACNU and O6-ethylguanine on rat subcutaneous gliomas]. 188 22

Hyperthermia increases the cytotoxicity of the nitrosourea BCNU (carmustine). Glucose given before treatment may further increase the value of thermochemotherapy, presumably by lowering tumour pH through blood flow reduction. The water-soluble ACNU (nimustine) is an alternative to other nitrosoureas in the treatment of gliomas. The drug is soluble without use of ethanol, and the eye complications when given intra-arterially are reduced compared with similar use of BCNU. The influence of simultaneous hyperthermia on treatment with ACNU, and the value of glucose administered before thermochemotherapy therefore were investigated in the malignant rat glioma BT4An. BD IX rats with subcutaneous BT4An tumours on the hind leg were treated with ACNU (i.p.), or ACNU and locally applied waterbath hyperthermia (44 degrees C for 45 min), with or without previous glucose (6 g/kg i.p. 2 hours before treatment). ACNU (10 or 20 mg/kg) alone and ACNU (20 mg/kg) after previous glucose did not influence tumour growth, compared to the controls. Simultaneous ACNU (10 mg/kg) and hyperthermia clearly was more effective than treatment with hyperthermia alone. Glucose load before treatment further enhanced the effect of combined ACNU and hyperthermia. Glucose before treatment did not change local toxicity or weight profiles of treatment with ACNU alone, or simultaneous ACNU and hyperthermia. Glucose load therefore represented a therapeutic gain when administered before thermochemotherapy with ACNU.
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PMID:Thermal enhancement of ACNU and potentiation of thermochemotherapy with ACNU by hypertonic glucose in the BT4An rat glioma. 189 66

To predict the efficacy of anticancer drugs such as ACNU [1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl-3-nitrosoure a hydrochloride] and MCNU [1-(2-chloroethyl)-3-(methyl-alpha-D-glucopyranos-6-yl)-1-nitrosou rea] in the treatment of malignant gliomas, the usefulness of the chick embryo assay as a chemosensitivity test was studied. Fifty-seven surgical specimens including benign tumors were examined by this method. All tumor specimens tested could be grafted on the chorioallantoic membrane of chick embryo; the evaluable ratio was 100%. Twenty-one patients with previously untreated malignant glioma could be evaluated to test the predictability of the clinical effects, judged by computed tomography. There were 7 (78%) instances in which the assay response corresponded to a clinical partial response (true-positive). There were 2 (22%) false-positives for the assay, 0 (0%) false-negative and 12 (100%) true-negatives. The over-all predictive accuracy was 90% (19/21). Thus, a high-degree of positive association exists between the chick embryo assay and the clinical outcome. This in vivo assay system for malignant glioma is advantageous for chemosensitivity tests because of its convenience, rapidity, and inexpensiveness.
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PMID:Chick embryo assay as chemosensitivity test for malignant glioma. 195 82

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

Three ACNU-resistant clones (R1, R3, and R12) were isolated from 9L rat glioma cells under selection pressure of ACNU in vitro. The authors have investigated the mechanisms of resistance and characteristics of these clones at the cellular level by studying cross-resistance patterns to chemical and physical agents. Although these resistant sublines showed complete cross-resistance to methyl-chloroethylnitrosourea (MCNU), no cross-resistance was observed for other alkylating agents, while each of the resistant sublines showed partial cross-resistance to structurally dissimilar toxic agents (vinblastine, Adriamycin, and VP-16). No difference in ACNU uptake was observed between 9L and R3 cells, and resistance patterns among alkylating agents suggested that the mechanism of ACNU resistance was specific to bifunctional nitrosoureas. Based on a transport study, this multidrug resistance could be explained by reduced intracellular uptake of these drugs, but there seemed little possibility that membrane P-glycoprotein, which usually is observed in typical multidrug-resistant cells, was expressed in these ACNU-resistant cells because enhanced drug efflux was not found in ACNU-resistant sublines. Significant collateral sensitivity to L-asparaginase indicated that ACNU might disturb the asparagine synthetic pathways by its mutagenic action. The increased level of total glutathione in the resistant sublines may be one mechanism of radiation or ACNU resistance.
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PMID:Cross-resistance patterns in ACNU-resistant glioma sublines in culture. 207 67

FK973, a novel antitumor antibiotic, was obtained as a fermentation product of Streptomyces sandaensis. FK973 had excellent cytotoxic effects against in vitro cultured human glioblastomas, medulloblastomas, and murine glioma (203 glioma) cells. The antitumor effects were also well observed against ACNU resistant glioma cells. FK973 did not go through the blood-brain barrier. The median survival time (MST) of MG models treated with FK973 was 21 days. On the other hand, the MST of the control group was 15 days. In the in vitro assessment against neural disturbance, FK973 showed a little disturbance of murine brain cells but less toxic than ADM. In the in vivo neurotoxicity examination, FK973 showed no clear damage to the neural cells and myelin sheaths.
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PMID:[Antitumor activity of FK973 for malignant gliomas and its assessment for normal brain cells]. 207 87

The changes of cerebral blood flow (CBF) and metabolism of normal brain tissue after surgery, radiation, and chemotherapy in brain tumor patients were measured by positron emission tomography (PET). The subjects consisted of 6 men and 3 women, and were from 11 to 62 years old. Those were four patients with glioblastomas, one patient with malignant oligodendroglioma, one patient with astrocytoma grade II, one patient with astrocytoma grade III, one patient with pontine glioma, one patient with pineal germinoma. Seven patients were operated and pathohistologically diagnosed. Two patients with pineal germinoma and pontine glioma were not operated and radiologically diagnosed. Of 7 operated patients, first PET was performed before operation in 3 patients, and from 10 to 16 days after operation in 4 patients. Following first PET, the patients were treated with irradiation (1 case), or with both irradiation and chemotherapy (8 cases). The total radiation dose for tumor was from 59 to 61 Gy distributed in a period of 6-8 weeks. Whole brain irradiation was performed up to 30 or 40 Gy, with a remaining dosimetry (20-30 Gy focused on the tumor field. Chemotherapy consisted of intravenous administration of ACNU and oral administration of FT-207. Second PET was performed 1 month after therapy (9 cases), and third PET was performed from 4 to 24 months after therapy (6 cases). Fourth PET was performed in 2 patients (22 and 35 months after therapy), and fifth PET was performed in one patient (35 months after therapy).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The changes of cerebral blood flow and metabolism of normal brain tissue after surgery, radiation, and chemotherapy in brain tumor patients: evaluated by position emission tomography]. 207 54

Chemosensitivity assays including colony forming assay (CFA), MTT dye reduction assay (MTT assay) and thymidine incorporation assay (TIA) for cultured rat and human glioma cells were conducted to determine the correlation among them and the in vivo antitumor efficacy of anticancer drugs using rats implanted glioma cells. Cytotoxicity of various agents such as ACNU, ACR, CDDP, VCR or BLM, was estimated from the concentrations which caused 50% inhibition of the cell growth at the peak plasma concentration. The survival time of tumor bearing rats was assessed after ip treatment with these agents at their estimated clinical doses. This parameter was greater in the drugs that were shown to be highly sensitive in CFA and was consistent with the data for CFA. In the chemosensitivity assays, CFA closely correlated to MTT assay for all agents except VCR, but poorly so to TIA. The results in this study indicate that MTT assay seemed to be useful for determining the chemosensitivity of anticancer drugs and that chemosensitivity assay should be conducted depending on the nature of anticancer drug.
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PMID:[Chemosensitivity assays for malignant gliomas]. 224 Nov 89

The 6-day subrenal capsule assay for determining chemotherapeutic sensitivities of brain tumors was studied. Rat glioma 9L and ACNU resistant 9L-2 were transplanted under the renal capsule of normal immunocompetent WKA rats for laboratory investigation. Evaluation of implanted tumor growth till 12 days was performed. The effects of chemotherapeutic agents administered intravenously were evaluated by measuring the growth rate of implanted tumor specimens. The results obtained from SRC were compared with the results from colony forming assay. Both were correlated to each other. On the other hand, histological investigation revealed that implanted human tumor cells had been diminished and implanted tumor was replaced by immunoreactive cells from the host in many cases. These results threw doubt on a reliability of SRC. To avoid this immunoreaction, cyclophosphamide was injected as immunosuppressive agent subcutaneously 24 hours before implantation. In such cases, the growth rates of implanted tumors were increased and histologically the implanted tumor cells existed for 6 days after implantation. Twenty-three malignant brain tumors (malignant astrocytomas 16, metastatic tumors 5, malignant lymphoma 2) were obtained as surgical specimens. Evaluable assay rate of our study were 89%. 15 patients with malignant astrocytomas were studied about correlation between the sensitivities of ACNU and post-operative clinical courses. Overall clinical correlation of 15 cases of malignant astrocytomas was 47%. These results from subrenal capsule assay are not seemed to be beneficial for clinical use. Immunoreactive response when using immunocompetent rats must be solved in future.
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PMID:[Chemotherapy responsiveness of brain tumors in subrenal capsule assay]. 232 45

Responsiveness of seven human glioma xenografts to seven antitumor agents was investigated by an sc-iv system and the efficacies of these agents against human glioma were evaluated in terms of response rate. When their maximum tolerated doses were used, experimental response rates of nimustine (ACNU), vincristine (VCR), adriamycin (ADR) and vinblastine (VLB) were as high as 86-100%, while that of mitomycin (MMC) was 57%, and those of 5-fluorouracil (5-FU) and methotrexate (MTX) were 0%. On the other hand, when the doses pharmacokinetically equivalent to their clinical doses were employed, the response rate of ADR was the highest, followed by VCR and ACNU in this order. These results suggest that gliomas are significantly responsive to various antitumor agents in this sc-iv system.
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PMID:Responsiveness of subcutaneous human glioma xenografts to various antitumor agents. 233 29


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