Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tamoxifen has been shown to inhibit the proliferation of human gliomas in vitro. This inhibition is independent of tamoxifen's known anti-estrogenic properties. Tamoxifen is an inhibitor of protein kinase C (PKC), a calcium- and phospholipid-dependent serine kinase which plays a critical role in the proliferation of certain cell lines. Gliomas overexpress PCK, and their growth rate is coupled to the level of this key enzyme. As such, the effect of tamoxifen may be mediated by its inhibitory effect on PKC. To further investigate this possibility, we compared the chemosensitivity of cultured glioma lines to both tamoxifen and N-desmethyltamoxifen (DMT). DMT is the major metabolite of tamoxifen in humans and is a ten-fold more potent inhibitor of PKC. Seven lines were tested using the standard MTT assay, which quantitates metabolically active cells colorimetrically using a tetrazolium dye. Four of the seven lines were also tested using a tritiated thymidine uptake assay. In the MTT assay, all seven lines showed significantly greater sensitivity to DMT, while three of the four lines tested in the thymidine uptake assay were more sensitive to DMT. Correlation between the two assays was good. The dose of tamoxifen required to produce a 50% inhibition of optical absorbance or thymidine uptake (ID50) was typically five- to ten-fold greater than the ID50 for DMT, approximating the relative strength of the two compounds as PKC inhibitors. In addition to providing some support for the ypothesis that triphenylethylenes inhibit gliomas via PKC inhibition, these findings have clinical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:A comparison of the relative chemosensitivity of human gliomas to tamoxifen and n-desmethyltamoxifen in vitro. 796 94

Chemotherapy results in glioma are poor. In addition to chemotherapy most patients are treated with dexamethasone (Dex) to reduce brain edema. Therefore we examined the influence of Dex on the sensitivity of C6 glioma cells to methotrexate (MTX) using MTT-tests. The LD50 of MTX was 3*10(-8)M, 10(-7)M, 4*10(-6)M and 4*10(-4)M after 72, 24, 6 and 1 hour treatment, respectively. After incubations with combinations of Dex and MTX, twice as many cells survived high MTX concentrations. This protection could be overcome by addition of 10 to 100 fold more MTX. It was not species-specific since the effect was also found in human TE671 cells.
 ...
PMID:Dexamethasone induced partial resistance to methotrexate in C6-glioma cells. 797 89

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.
 ...
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 effect of mouse interferon alpha/beta (MuIFN alpha/beta) on the production of glycosaminoglycans (GAGs) by mouse glioma G-26 in vitro was evaluated. Two GAG species secreted extracellularly by the mouse glioma G-26 were isolated using cellulose acetate electrophoresis. They were identified as hyaluronic acid (HA) and chondroitin sulfate (CS) following enzymatic digestion with enzymes: hyaluronidase and chondroitinase ABC. Further characterization of CS by enzymatic digestion with specific chondroitinases for chondroitin 4-sulfate (CSA) and chondroitin 6-sulfate (CSC), revealed that the isolated CS was neither CSA nor CSC. Therefore, it may be either chondroitin sulfate B (CSB) (dermatan sulfate) or one of the 'chondroitin sulfate isomers' (D-H). The three day incubation of glioma G-26 cells with 8 x 10-8 x 10(4) U/ml of MuIFN alpha/beta resulted in a dose dependent inhibition of cell proliferation measured by 3H-thymidine incorporation and the MTT assay. The significant decrease of the CS (p < 0.008) but not the HA level, (measured densitometrically), was observed following 72 hours (hrs) incubation of G-26 cells with 8 x 10(3) U/ml of MuIFN alpha/beta (IFN treated cells: 0.03 +/- 0.007 integrated optical density (IOD); control cells: 0.07 +/- 0.01 IOD). The decreased CS production may be the underlying cause of IFN mediated inhibition of glioma cell proliferation.
 ...
PMID:Interferon effect on glycosaminoglycans in mouse glioma in vitro. 805 39

The secosteroid 1,25-dihydroxyvitamin D3 (1,25 (OH)2D3) is the major biologically active metabolite of vitamin D. Antitumor activity of this hormone has been observed on several cell lines and on breast cancer in vivo. The purpose of this in vitro study was to determine the possible effect of 1,25(OH)2D3 on glioma cells. Two glioma cell lines from rat (C6) or human (GHD) origin were cultured in the presence of 1,25(OH)2D3. The sensitivity of these cells to 1,25 (OH)2D3 was assessed with a colorimetric MTT assay. A cytotoxic effect of 1,25(OH)2D3 was detected at concentrations around 10(-8) M. A lag period of 3 days was required between the onset of the treatment and the observation of the effects. However, the continuous presence of 1,25(OH)2D3 is not required since cell death occurred even when C6 cells were challenged for 24 hr with 1,25(OH)2D3 and then cultured in the absence of the hormone. In addition, 1,25(OH)2D3 regulates the expression of its own receptors in C6 glioma. These results provide to our knowledge the first evidence for a cytotoxic effect of 1,25(OH)2D3 on rat and human glioma cells and could offer both an experimental model to study a programmed cell death in a brain-derived cell line and a new strategy for the inhibition of glioma growth in vivo.
 ...
PMID:Induction of glioma cell death by 1,25(OH)2 vitamin D3: towards an endocrine therapy of brain tumors? 815 34

Autocrine growth due to dysregulation of growth factor production may have a role in the development of neoplasia. We demonstrated that U251MG, a well characterized human malignant glioma cell line, had high affinity receptors for epidermal growth factor (EGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) by enzyme-linked immunosorbent assay. We assessed the inhibitory effect of anti-EGF receptor (EGFR), anti-FGF, and anti-PDGF monoclonal antibodies (MoAbs) on the growth of U251MG cells using the MTT assay and 3H thymidine uptake. At 50 micrograms/ml, the EGFR, FGF, and PDGF MoAbs significantly decreased cell numbers by 31.0%, 31.2%, and 31.0%, respectively, when compared to control cultures in the MTT assay. At the same concentration, the EGFR, FGF, and PDGF MoAbs reduced 3H thymidine uptake by 45.2%, 41.1%, and 40.0%, respectively, when compared to control cultures. At 50 micrograms/ml, a combination of the 3 MoAbs (16.6 micrograms/ml each) caused a 13.7% greater decrease in cell numbers in the MTT assay and an 11.9% greater decrease of 3H thymidine uptake. These findings suggest that the antigrowth factor MoAbs interrupted the autocrine loop at the growth factor receptor level. In conclusion, the demonstration that MoAbs directed against EGFR, FGF, and PDGF inhibit the growth of malignant glioma cells in vitro raises the possibility that these antibodies could be used clinically to treat malignant glioma either alone or conjugated to other agents.
 ...
PMID:[Growth control of a human glioma cell line by multiple autocrine loop blockade]. 816 53

The in vitro effect of ascorbyl esters (ascorbyl-stearate [As-S] and -palmitate [As-P]) and interferon (recombinant human interferon-a2b [rHuIFN-a2b]) on human glioma (U-373) cell proliferation, viability and glutathione-S-transferase (GST) activity was studied. The effect of As-S, As-P and rHuIFN-a2b on cell proliferation and viability was evaluated by [3H] Thymidine incorporation and colorimetric MTT assays, respectively. Incubation of glioma cells with As-S, As-P or rHuIFN-a2b for 24 h resulted in a dose dependent inhibition of cell proliferation (IC50 = 68.0 microM As-S, 86.0 microM As-P and 47.3 Units/ml rHuIFN-a2b), and moderate decrease of cell viability. It was found that As-S was a more efficient inhibitor of cell proliferation, viability and GST activity than As-P. GST from U-373 cells was purified. The activity of purified GST towards 1-chloro-2,4-dinitrobenzene (CDNB) was inhibited in a dose dependent manner by ascorbyl esters (I-50 = 27.5 microM As-S and 56.0 microM As-P) but not by rHuIFN-a2b. GST activity of cytosol isolated from U-373 cells which were previously treated with As-S (150 microM) or rHuIFN-a2b (150 units/ml) for 0, 2, 5, 10, 20 and 30 min was sharply decreased during 5 to 10 min of treatment and increased at longer durations of treatment.
 ...
PMID:Inhibition of human glioma cell proliferation and glutathione S-transferase by ascorbyl esters and interferon. 823 23

Mouse glioma-26 (G-26) cell line established in this laboratory was used in the study. The in vitro effect of ascorbyl esters, viz., ascorbyl-palmitate (As-P), -stearate (As-S) and mouse interferon-alpha/beta (MulFN-alpha/beta) on the glioma cell viability, proliferation and glutathione S-transferase (GST) activity was investigated. Cell viability and proliferation were examined by colorimetric MTT assay and [3H]-thymidine incorporation, respectively. Incubation (24h) of G-26 cells with As-S, As-P or MulFN-alpha/beta, resulted in a dose dependent decrease in cell viability (IC50 = 125 microM As-S; 175 microM As-P and 3.6 x 10(4) U/ml MulFN-alpha/beta) and proliferation (IC50 = 157 microM As-S; 185 microM As-P and 3.6 x 10(4) U/ml MulFN-alpha/beta). A combined exposure to 175 microM As-S and 800 U/ml of MulFN-alpha/beta resulted in a greater than an additive effect on cell viability and proliferation. The inhibition of cell proliferation/viability by interferon was species specific and was observed only with homologous MulFN-alpha/beta, but not with human interferon-alpha lymphoblastoid or human interferon-beta. Ascorbyl esters inhibited cytosolic GST activity (1-50 = 15.0 microM As-S and 28.5 microM As-P) towards 1-chloro-2,4-dinitrobenzene in a dose dependent manner. The apparent Ki values for affinity purified GST, deduced from Dixon plots were 0.95 microM and 2.0 microM for As-S and As-P, respectively. Significant inhibition of GST was also observed in the cytosol isolated from G-26 cells exposed to 300 microM As-S or 800 U/ml MulFN-alpha/beta.
 ...
PMID:Inhibition of cell proliferation and glutathione S-transferase by ascorbyl esters and interferon in mouse glioma. 841 Jan 36

Pharmacokinetics and antitumor activity of MX2.HCl (MX2), a new morpholino anthracycline, were investigated in rats transplanted 9L gliosarcoma cells in the brain. (1) Pharmacokinetics: AUC of MX2 in the brain tumors which received intracarotid and intravenous injection of 2mg/kg of MX2 were 117.50 and 55.94 micrograms.hr/g, respectively. AUC of the brain tissue was 1.38-3.90 micrograms.hr/g. (2) Antitumor activity: The inhibition of cell growth at the concentration of 0.1 micrograms/ml was 73.1% with MTT assay. The mean survival time in tumor-bearing rats after intracarotid and intravenous injection of 2mg/kg of MX2 prolonged significantly. Therefore, it seems that MX2 will become an efficacious drug for the treatment of malignant glioma.
 ...
PMID:[Pharmacokinetics and antitumor activity of MX2, a new morpholino anthracycline in brain tumor intracerebral transplanted in rats]. 847 Sep 21

Malignant glioma patients are sometimes treated with cisplatinum (CDDP) and dexamethasone (DEX). The question, was addressed as to whether DEX induces cellular resistance to CDDP using the C6 glioma cell line in MTT-tests. 50% of the cells were killed by 2 x 10(-5) M, 5 x 10(-6) M, and 7 x 10(-7) M CDDP after 2, 24, and 72 hours of incubation, respectively. 10-6M DEX treatment protected C6 cells from CDDP 5 x 10(-5) M 72 hours, resulting in twice as many surviving cells, [p<0.01(t-test)]. This protection was also observed in human TE671 rhabdomyosarcoma and T98G human glioma cells but not in A172 human glioma cells. It was mediated by glucocorticoid receptors and increased glutathione. DEX reduced the sensitivity of C6 cells also to carboplatinum, doxorubicin, actinomycin D, cytosine-arabinoside and methotrexate but not to 4-hydroxyifosfamide, vincristine, radiation, 6-mercaptopurine or thioguanine. These data suggest a more restricted use of DEX during chemotherapy of brain tumour patients.
 ...
PMID:Dexamethasone induces partial resistance to cisplatinum in C6 glioma cells. 868 32


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>