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)

Interferons (IFNs) are a natural body defense with powerful effects on tumor growth, including gliomas. The direct effects of IFN-gamma on (1-4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU)-induced deoxyribonucleic acid (DNA) damage and cytotoxicity were investigated in two human glioblastoma cell lines, A-172 and T98G, using a single cell microgel electrophoresis technique and a microculture tetrazolium assay. The results demonstrated a synergistic effect of IFN-gamma with ACNU on intracellular damage in both cell lines. 10 micrograms/ml ACNU induced a cell inhibition rate of 23.9% in A-172 cells, and almost no effect on T98G cells. 1000 U/ml IFN-gamma and 10 micrograms/ml ACNU caused a significant increase in cell inhibition, 51.2% for A-172 and 72.3% for T98G cells. DNA damage in individual A-172 and T98G cells exposed to ACNU was enhanced significantly by IFN-gamma (p < 0.001). The findings suggest a direct effect of IFN-gamma on ACNU-induced cell damage in human glioma, in addition to its effect on immunomodulation.
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PMID:Effect of interferon-gamma on ACNU-induced DNA damage and cytotoxicity in human glioblastoma cells. 768 31

Several anticancer drugs have recently been shown to induce cell death in a manner similar to programmed cell death or apoptosis. The purpose of this study is to explore the mode of cell death caused by ACNU, a water-soluble nitrosourea. Exposure of rat glioma cell line KEG-1 to ACNU for 2 hours resulted in oligonucleosomal DNA fragmentation, creating a 'ladder' on agarose gel electrophoresis. DNA fragmentation began 18 hours after ACNU treatment, and preceded loss of membrane integrity as evaluated by the trypan blue exclusion test. The extent of DNA fragmentation increased in a dose-dependent manner, and the cell survival rate decreased reciprocally. A translational inhibitor, cycloheximide, suppressed this DNA fragmentation and enhanced cell survival rate with partial inhibition of protein synthesis. However, a transcriptional inhibitor, actinomycin D, failed to inhibit DNA fragmentation or enhance cell survival. Cycloheximide-inhibitable DNA fragmentation was also found in the KEG-1 implanted in vivo rat model following the administration of ACNU. These findings suggest that ACNU induces cell death associates with DNA fragmentation and partially with protein synthesis.
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PMID:Cell death due to ACNU-induced DNA fragmentation: inhibition by cycloheximide. 771 48

This study investigated the independent and combined effects of photodynamic therapy (PDT), laser photodynamic hyperthermia (LPDH) and 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl) -3-nitrosourea hydrochloride (ACNU) in a rat 9L induced gliosarcoma model. The mortality rate (MR60), mean survival time (MST60), and increasing life span (ILS60) within 60 days were determined to evaluate the therapeutic effect in vivo. The MR60 and MST60 of the gliosarcoma tumor control were 100% and 16.2 days. The ILS60s of PDT and ACNU were 72.84% and 49.81%, respectively, but MR60 of both were 86.72%. All combined treatments produced significantly prolonged survival (P < 0.01). The combined effects of LPDH and ACNU, MR60, MST60, and ILS60 were 60%, 43 days, and 165.4%, respectively. The ILS60 of PDT + ACNU (96.48%) and PDT + LPDH (98.58%) also indicated a synergistic or additive effect. The survival fraction and synthetic rate of DNA, RNA, and protein of glioma 9L tumor cells in vitro after single treatment of PDT or combined with antitumor drugs and laser showed that the cytotoxicity of PDT to 9L tumor cell was obvious by using Rh123, HPD, and Pf-II as photosensitizers. Combined treatments of PDT, antitumor drugs, and laser suppressed the synthesis of DNA, RNA, and protein more significantly than single treatment with PDT.
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PMID:Therapeutic effects of photosensitizers in combination with laser and ACNU on an in vivo or in vitro model of cerebral glioma. 777 98

Ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), a water soluble nitrosourea with log P -0.71, may be efficacious in the treatment of subarachnoid dissemination of malignant glioma. We used 2 dogs to study the neurotoxicity and pharmacokinetics of MCNU. MCNU (1 mg), dissolved in 10 ml of artificial CSF, was administered via the right lateral ventricle during a period of 18 to 42 min and the CSF was drained by lumbar puncture. The perfusion was repeated once a week for 10 consecutive weeks. No neurological and systemic symptoms were noted after perfusion. Histological examination of the brain and spinal cord showed local denudation of the ependyma and local subependymal spongy degeneration and gliosis in the lateral ventricle into which MCNU was administered in one dog and local denudation of the ependyma in the other. When administration was over a period of 21 to 38 min, the MCNU concentration in the lumbar CSF peaked at 11.11 to 50.67 micrograms/ml, in 28 to 78 min. The area under the drug concentration-time curve (AUC) was 1152 micrograms x min/ml on average, significantly larger than that of ACNU. The elimination phase followed linear kinetics and the half-time was 41.1 min on average, significantly longer than that of ACNU. These findings suggest that ventriculolumbar perfusion of MCNU may be effective in the treatment of subarachnoid dissemination of malignant glioma notwithstanding some local histological changes.
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PMID:Neurotoxicity and pharmacokinetics of ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) in dogs. 780 74

It has recently been shown that the bcl-2 gene is involved in the growth and development of certain tumors by suppressing apoptosis. To explore the possible involvement of the Bcl-2 protein in gliomas, three human glioma cell lines (T98G, A172, and U251) were examined for the presence of this protein. It could be documented by confocal laser microscopy that the Bcl-2 protein was localized mainly in mitochondria and nuclear membrane of T98G cells. Flow cytometric analysis revealed that 71-87% of the cultured glioma cells expressed the Bcl-2 protein. Treatment of U251 cells with ACNU for 24 h induced increased Bcl-2 protein expression; induction was dose dependent. Exposure of T98G and A172 cells to ACNU did not affect their Bcl-2 protein levels. Southern blot analysis revealed no chromosomal translocation in the cells studied. These findings suggest that Bcl-2 protein overexpression in glioma cells may partly contribute to tumor growth and tolerance to chemotherapeutic agents.
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PMID:Induced expression and subcellular localization of the Bcl-2 protein in cultured glioma cells. 789 19

Resistance to multiple drugs is often observed in malignant gliomas. The authors used a microtiter tetrazolium test to analyze primary in vitro chemoresistance and chemosensitivity of 15 early cultures of human malignant glioma exposed to 50 micrograms/ml (1,4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosoure a (ACNU), 50 micrograms/ml cisplatin, 1 microgram/ml vincristine, or combinations of these chemotherapeutic agents. Primary chemoresistance was observed in 87% of tumors for ACNU, in 87% for cisplatin, and in 83% for vincristine. All tumors were examined for expression of multidrug-resistant p-glycoprotein, a transport protein of 170,000 D, by means of immunohistochemical staining with the JSB-1 antibody on paraffinized tumor sections. Eight of 15 specimens (53%) showed positive staining for the monoclonal antibody. Primary chemoresistance was overcome by addition of the calcium antagonists verapamil or nimodipine to the cultures if the original tumor expressed p-glycoprotein (p < 0.01 for verapamil, p < 0.05 for nimodipine). In tumors not expressing p-glycoprotein, addition of calcium antagonists to the cell cultures did not influence primary chemoresistance. It is concluded from these data that addition of calcium antagonists to the adjuvant chemotherapy of malignant gliomas might overcome primary chemoresistance in tumors expressing the multidrug-resistant phenotype.
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PMID:Reversal of chemoresistance in malignant gliomas by calcium antagonists: correlation with the expression of multidrug-resistant p-glycoprotein. 793 93

We analysed long-term follow-up results of 175 patients with malignant glioma (110 glioblastoma and 65 anaplastic astrocytoma) treated under five different regimes during the past two decades. The factors of age (less than 40), histology (anaplastic astrocytoma) and type of adjuvant therapy (radiation and chemotherapy) contributed to long survival. The other important factor was the response to adjuvant therapy. Cases of gross total removal or complete response (CR) of a residual tumour to an adjuvant therapy showed a better prognosis. The three and five year survival rate was 42% and 24%, respectively. The highest CR ratio (23%) was seen in patients treated by intravenous injection of interferon and ACNU in addition to radiotherapy (IAR therapy).
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PMID:Long-term follow-up results of 175 patients with malignant glioma: importance of radical tumour resection and postoperative adjuvant therapy with interferon, ACNU and radiation. 753 70

A simple and convenient technique for in situ quantification of DNA damage induced by 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloro-ethyl)-3-nitrosourea hydrochloride (ACNU) an alkylating agent, or irradiation was demonstrated in C6 glioma cells using a single cell gel electrophoresis. Treatment with ACNU or irradiation caused a dose dependent DNA damage which was detected by measuring the length of migration of fragmentary DNA in individual cells. Wild type C6 cells treated with ACNU (0, 10, 30, 60 micrograms ml-1) for one hour showed longer distance of migration of DNA than the ACNU-resistant subtype cells (C6R), indicating that ACNU-sensitive C6 cells were more vulnerable to ACNU than C6R cells. The results of DNA migration in C6 and C6R cells treated with ACNU were consistent with that from MTT assay which had been regarded as a standard method for chemosensitivity test. Furthermore, a time course study for DNA repair activity of C6 and C6R cells was also performed by measuring the length of DNA migration after incubation (0, 15, 30, 60, 120 min) of cells treated with 60 micrograms ml-1 ACNU. C6R cells repaired DNA damage more rapidly than C6 cells. In addition, the technique was also used to measure the DNA damage in C6 cells exposed to 0, 2, 6, 8, 10 Gy of x-ray irradiation, and a dose-dependent DNA migration after radiation injury was observed. This technique appears to be simple and useful for assessing chemosensitivity or radiosensitivity in individual glioma cells.
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PMID:A single cell gel electrophoresis technique for the detection of DNA damage induced by ACNU, an alkylating agent or irradiation in murine glioma cell lines. 798 53

The pathophysiology and treatment of malignant brain tumors (malignant glioma, metastatic brain tumor and malignant lymphoma) were discussed. In order to improve the prognosis of malignant brain tumor patients, many clinical trials have been conducted. The most acceptable treatment for malignant glioma is surgical resection plus radiochemotherapy with ACNU. A multidisciplinary approach to treatment is important for control of metastatic brain tumors. Treatment of malignant lymphoma includes radiotherapy and chemotherapy in combination. Combination chemotherapy with CHOP is more effective for malignant lymphoma.
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PMID:[Treatment of malignant brain tumor]. 806 Jan 32

In order to study the dynamic relationship in glioma cells between O6-alkylguanine-DNA alkyltransferase (AGT) activity and resistance to the cytotoxic effect of chloroethylnitrosoureas (CENUs), we investigated the changes in sensitivity to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) after modulation of AGT activity. In ACNU-resistant rat glioma cell lines (9LR1, 9LR3, and 9LR12) and a human glioma cell (HNG-1), O6-methylguanine enhanced cytotoxicity to ACNU following a depletion of AGT activity. But no enhancement of cytotoxicity was seen in an ACNU-sensitive rat glioma cell line (9L). In the 9L and 9LR12 cells, equivalently sublethal doses of ACNU similarly depleted AGT activity but the regeneration rates of this repair protein were different. In the case of a 7-day pretreatment with human recombinant interferon-beta (HuIFN-beta), although it could modulate AGT activity in HNG-1 cells, no definite influence on cellular sensitivity to CENUs was observed. However, a 50-day pretreatment with HuIFN-beta conferred resistance to CENUs on them despite its effect to reduce AGT activity. Thus, diversity was seen in the relation between AGT activity and resistance to CENUs when AGT activity was modulated by HuIFN-beta. The results of this study suggest that AGT activity is one of factors affecting cellular sensitivity to CENUs but that alternative mechanisms of tolerance may be induced depending upon some environmental effects.
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PMID:Interrelationship between O6-alkylguanine-DNA alkyltransferase activity and susceptibility to chloroethylnitrosoureas in several glioma cell lines. 812 May 66


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