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)

A subclone of a human glioma tumor cell strain which was deficient at O-6-alkylguanine repair was transfected with DNA from an O-6-alkylguanine DNA alkyltransferase-positive human colon tumor cell line (HT29). The transfected subclone, which was selected by its resistance to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), acquired increased resistance to chloroethylnitrosourea (CNU), contained O-6-methylguanine-DNA methyltransferase activity, and failed to accumulate interstrand crosslinks in its DNA upon treatment with CNU. The subclone morphologically resembled its CNU-sensitive parental glioma cell strain. The close correlation between the increased cellular resistance, increased O-6-alkylguanine repair activity and the absence of crosslinking suggests that the formation of DNA crosslinks is one important mechanism of cytotoxicity produced by CNU, and that repair of DNA lesions by O-6-alkylguanine DNA alkyltransferase may partially prevent CNU-induced cytotoxicity.
Carcinogenesis 1986 Sep
PMID:Transfection of DNA from a chloroethylnitrosourea-resistant tumor cell line (MER+) to a sensitive tumor cell line (MER-) results in a tumor cell line resistant to MNNG and CNU that has increased O-6-methylguanine-DNA methyltransferase levels and reduced levels of DNA interstrand crosslinking. 374 31

Metoclopramide (MCA), a N-substituted benzamide, causes DNA strand breaks and inhibits DNA repair in vitro and sensitizes radiation and chemotherapeutic drugs in human squamous cell carcinomas when xenographed into nude mice or in a rat glioma model. Here we report on the evaluation of the mechanism behind the radiosensitizing effects of MCA. DNA damage was measured in vivo in a CBA-mouse tumor line (A12B3, sarcoma tumor) by using both alkaline elution and nucleoid sedimentation analysis of cell suspensions prepared from either resected tumor, spleen tissues or whole blood samples. The amount of DNA damage caused by radiation alone, measured 30 min after the irradiation was started, was dose dependent up to 18 Gy in all tissues. The radiation-induced DNA damage in tumor tissue was elevated compared to radiation alone in the presence of MCA, but the level was not higher at 18 Gy compared to 6 Gy in the presence of MCA, and it was still not fully repaired 12 h after irradiation. HPLC analysis of the NAD pools in tumor tissue after DNA damage induction showed a delay in the recovery of the NAD pools (presumably due to the presence of still unrepaired DNA) after exposure to MCA (2 mg/kg) + radiation (6 Gy) compared to tumors exposed to radiation (6 Gy) only, which were fully restored after 48 h. These data confirm earlier published in vitro data on MCA as an inducer of DNA damage and an effector of DNA repair. In addition, the in vivo measurement of radiation-induced DNA damage and DNA repair using the nucleoid sedimentation and alkaline elution assays together with NAD pool determinations may prove to be effective intermediate endpoints in the evaluation of drugs as potential radiosensitizers.
Carcinogenesis 1995 May
PMID:In vivo tumor measurement of DNA damage, DNA repair and NAD pools as indicators of radiosensitization by metoclopramide. 776 61

Single-stranded DNA binding proteins (SSBs) are those proteins which preferentially bind single-stranded DNA as opposed to double-stranded DNA and are known to be involved in recombination, amplification, and repair of DNA. To characterize single-stranded DNA binding proteins of glial cells and to examine their potential involvement in induction of neurogenic tumors in rats, nuclei were isolated from target glia and non-target liver of carcinogenically sensitive Sprague-Dawley (SD) and resistant Berlin-Druckrey-IV (BD-IV) rats of various ages and rapidly proliferating glioma cells. Nuclei were fractionated into chromatin, a preribosomal RNA protein complex, heterogeneous nuclear ribonucleoprotein complex (hnRNP), and nucleoplasm. SSBs were isolated, quantitated, and characterized by electrophoresis. A comparison of the contents of SSBs relative to RNA and their electrophoretic profiles between chromatin and hnRNP revealed that SSBs of liver chromatin were mainly associated with RNA. However, it was found that glial chromatin, particularly that of juvenile rats, was enriched with a heterogeneous series of SSBs which were not found in liver chromatin and presumably associated with chromosomal DNA. Some of these SSBs were enriched in glial chromatin of sensitive SD rats compared with that of resistant BD-IV rats. High mobility group proteins (HMG) 1 and 2 constituted major SSB components in the nucleoplasm and a greater amount of these HMGs were found in juvenile glia, compared to adult glia and juvenile and adult liver. Fractionation of glial SSBs and determination of their biological functions may contribute to the further understanding of the role these proteins may play in the processes of carcinogenesis.
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PMID:Characterization of single-stranded DNA binding proteins in rat glial-enriched nuclei. 785 31

In a population-based case-control study of 416 incident gliomas in adults carried out in Melbourne, Australia, between 1987 and 1991, 409 age-sex-matched case-control pairs (243 male and 166 female) had adequate data available to examine associations between the dietary intake of N-nitroso compounds, N-nitroso precursors, other nutrients including N-nitroso inhibitors, and the risk of glioma. Dietary intakes were based on the reported frequency of consumption of 59 food items. Increased odds ratio (OR) were observed in males who consumed high levels of bacon, corned meats, apples, melons and oil. OR less than unity were observed in men consuming cabbage and cola drinks, and in women who consumed wholegrain bread, pasta, corned meat, bananas, cauliflower, brocoli, cola drinks and nuts. Generally, N-nitroso associations were greater in men and micronutrient associations were greater in women. Elevated OR in men, but not women, were associated with the intake of N-nitroso dimethylamine (NDMA), retinol and vitamin E. The intake of nitrate (largely of vegetable origin) was protective in women but not in men. When analyzed using multiple logistic regression, the association with NDMA intake in males was not modified by dietary micronutrient intakes. In females, beta carotene alone, though not directly associated with risk, modified the effect of NDMA. On balance, this study added only limited support to the N-nitroso hypothesis of glial carcinogenesis.
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PMID:Dietary factors and the risk of glioma in adults: results of a case-control study in Melbourne, Australia. 792 41

Gap junctional communication (GJC) is mediated by channels consisting of connexins and can be differentially regulated by ions, second messengers, kinases, phosphatases, and cell adhesion molecules. Tumor cells and oncogene-transformed cells often, but not always, show reduced homologous GJC between themselves. A more stringent correlation may exist between transformation and reduced heterologous communication between transformed cells and normal neighbors. Reduced GJC seems to stimulate tumor promotion but has no significant effect on the initiation phase of carcinogenesis. These effects may reflect the importance of intercellular passage of second messengers or other small molecules in cell growth control. Some evidence suggests that gap junction in combination with cell adhesion molecules can affect metastatic potential, but a clear picture has not yet emerged. Coupling and gap junction expression can be regulated both pre- and posttranslationally in oncogene-transformed cells. Src probably downregulates GJC in fibroblasts by tyrosine phosphorylation of connexin43. The Ras-induced reduction in GJC appears to be caused by decreased connexin expression. E1A, but not Myc and Fos, downregulates GJC to some extent. Artificial expression of connexin in glioma, hepatoma, chemically transformed, and src-transformed cells can restore GJC and suppress growth and/or tumorigenesis. These results argue for involvement of GJC in transformation and growth control.
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PMID:Gap junctional communication and neoplastic transformation. 824 23

In the early stages of brain carcinogenesis induced by transplacental administration of N-ethyl-N-nitrosourea to BD IX rats, a constant increase in the activity of cerebral diamine oxidase, the rate-limiting enzyme in terminal catabolism of polyamines, was observed. Gliomas, which developed between the fifth and eight month of extrauterine life, showed an 8-fold increase in enzyme activity compared with normal brain from rats of the same age. Concomitantly, an 11-fold enhancement in putrescine, a physiological substrate of diamine oxidase, was also found. Such findings indicate that an increase in oxidative putrescine catabolism via diamine oxidase takes place in transformed cells and in gliomas and is probably linked to an activation of polyamine synthesis and turnover.
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PMID:Diamine oxidase activity in rat brain carcinogenesis and in gliomas. 836 92

The inter- and intracellular distribution of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (ATase) may be an important factor in the sensitivity or resistance of tumours to treatment with certain alkylating agents, including the methyltriazenes and nitrosoureas. In order to examine this issue 26 human brain tumour sections (23 high grade gliomas and three low grade gliomas) were examined for ATase expression by immunohistochemistry using a rabbit anti-human ATase polyclonal antibody. Positive staining, seen as fine black granules mainly confined to the nucleus, was observed in all the glioma sections examined. There was marked cellular heterogeneity, ranging from cells completely devoid of staining to cells with very intense staining. Semi-quantitatively, in the 23 high grade gliomas examined six had 1+ staining, seven had 2+ staining and 10 had 3+ staining, whereas all three low grade gliomas had 1+ staining. These results are in contrast to published reports showing that approximately 35% of human brain tumour-derived cell lines and xenografts had very low levels of ATase activity and suggest that the complete lack of ATase is not a common occurrence in high grade glioma.
Carcinogenesis 1996 Apr
PMID:Inter- and intracellular heterogeneity of O6-alkylguanine-DNA alkyltransferase expression in human brain tumors: possible significance in nitrosourea therapy. 862 71

Accumulating evidence indicates that telomerase activity is stringently repressed in normal human somatic cells but reactivated in cancers and immortal cells, suggesting that activation of telomerase activity may play a role in carcinogenesis and immortalization. Recently, down-regulation of telomerase activity by induction of differentiation has been reported for cells of pre-myelocytic and myelocytic leukemia as well as embryonic carcinoma. To gain further insight about the regulation of telomerase activity following induction of differentiation, telomerase activity was examined in a human hematopoietic progenitor cell line (D2), a melanoma cell line (CM73-36) and a glioma cell line (Ast812) before and after addition of differentiation inducing agents. The state of differentiation was assessed by growth inhibition and cell morphological maturation. Telomerase activity was assayed by a PCR-based telomeric repeat amplification protocol (TRAP). Our data show that telomerase activity was inhibited only in differentiation-induced D2 cells but not in differentiation-induced melanoma and glioma cells. A model for the differential inhibition of telomerase activity following induction of differentiation in different cancer cells will be presented.
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PMID:Differential inhibition of telomerase activity during induction of differentiation in hematopoietic, melanoma, and glioma cells in culture. 926 30

Supranutrition dietary levels of the element selenium (Se) that have been shown to reduce or retard tumor development resulting from transplantation. The rat placental form of glutathione-S-transferase (GST-p) has been reported to be a good marker for pre-neoplastic or neoplastic lesions. Four groups of rats with glioma were exposed to Se-free, 0.05, 2.0, and 4.0 ppm sodium selenite GST-p was investigated. Normal brain tissue did not differ significantly in all groups. In contrast, GST-p in tumor was significantly higher in Se-free and 4.0-ppm groups compared to 0.5- and 2.0-ppm groups. The concentration of Se in normal brain tissue did not differ significantly in Se-supplement groups. By contrast, Se in tumors was significantly higher in the 0.5- and 2.0-ppm groups compared to the Se-free and 4.0-ppm groups. Mean group survival at 30 d after treatment was determined and compared with previous dietary Se. Survival was significantly longer in the 0.5- and 2.0-ppm groups than in the Se-free and 4.0-ppm groups. The 2.0-ppm group had enhanced survival, similar to the 0.5-ppm group. The Se-free and 4.0-ppm groups might have no protection against carcinogenesis.
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PMID:The decrement of carcinogenesis by dietary selenium and expression of placental form of glutathione-S-transferase in rat glioma. 928 62

Many cancer and immortal cells exhibit telomerase activity that stabilizes telomere lengths and may be involved in cell immortality and carcinogenesis. Downregulation of telomerase has been reported during differentiation of hematopoietic, melanoma, glioma, and myelocytic leukemia cells. Moreover, normal human mammary epithelial cells immortalized by a p53 mutant have been reported to exhibit activation of telomerase. However, no information is available about the activity of telomerase during p53-mediated apoptosis of immortalized cells. We investigated the activity of telomerase during p53-induced apoptosis of the immortalized endothelial cell line ECV-304. ECV-304 cells were induced into apoptosis by infection with a recombinant adenovirus that facilitated expression of high levels of wild-type p53. Telomerase activity was measured by a PCR-based telomeric repeat amplification protocol (TRAP). Telomerase activity was found to be unaffected by overexpression of p53 and apoptosis in immortalized endothelial cells.
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PMID:Telomerase activity in immortalized endothelial cells undergoing p53-mediated apoptosis. 943 61


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