Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biological effects of human natural tumor necrosis factor-alpha (TNF) on glioblastoma cells in vitro and on glioma patients were investigated. TNF treatment on glioblastoma cells, even at a high dose (256 U/ml), exhibited no remarkable cytocidal activity in MTT assay, but at lower doses significantly inhibited colony forming and DNA synthesis. TNF at a low dose (10 U/ml) stimulated production of prostaglandin E2, Mn-superoxide dismutase, interleukin (IL)-6 and IL-8 by glioblastoma cells. These results indicated that the direct effect of TNF on human glioblastoma cells is rather antiproliferative than cytotoxic and is to modulate their metabolic pathways. In an early Phase I clinical trial, TNF was administered intracranially to six patients bearing glioblastoma. In this trial, the author studied in vivo immunological responses in the cerebrospinal fluid and regional fluid after the regional TNF injections. TNF in these body fluids were detected with a half life of several hours. There occurred a substantial number of leukocyte migration after the TNF administration. Neutrophils appeared first peaking at 8 to 12 hours, and then CD4+CD8-T cells and CD11b+CD13+CD14+ monocytes followed. IL-8 activity in the cerebrospinal fluid simultaneously corresponded to peak of the neutrophil migration. Increases in IL-6, IL-1 beta and prostaglandin E2 levels in the cerebrospinal fluid, regional fluid or both occurred peaking at 8 to 12 hours after TNA infection. Neither IL-2 nor interferons was detected. In conclusion, TNF may act as an antineoplastic agent by its direct cytostatic effects and indirectly through immune modulatory effects.
 ...
PMID:[In vitro and in vivo immunobiological responses of glioblastoma to human natural tumor necrosis factor-alpha]. 142 94

Some reports have demonstrated that selenium can inhibit tumorigenesis in some tissues of animal. However, little is known about the inhibitory effect on malignant tumor cells of brain. The purpose of our study was to determine the biological effect of selenium on growth of rat glioma and human glioblastoma cell lines. Cell lines C6 and A172 were obtained from Japanese Cancer Research Resources Bank, Tokyo, Japan (JCRB). Cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% fetal calf serum at 37 degrees C in a humidified atmosphere of air and 5% CO2. Antiproliferative effects of selenium were evaluated using growth rate assay quantifying cell number by MTT assay. An antiproliferative effect of selenium was found in two cell lines, which was more effective on human A172 glioblastoma and less effective on rat C6 glioma.
 ...
PMID:Effect of selenium on malignant tumor cells of brain. 757 18

A survey of in vitro cytotoxic effects of camptothecin in human epitheliod sarcoma, colon, breast and ovarian carcinomas, glioblastoma, and neuroblastoma (PNET) cell lines, was done. We chose the MTT assay to measure survival and observed that 24 h exposures to camptothecin caused consistently greater toxicity than 1 h exposures. The LD50 for camptothecin was in the 12.5-25 ng/ml range. There was a 10-fold range of growth rates measured by OD after 5 days exposure and varied expression of MDR1 in these cell lines--none of which could be correlated with tumor sensitivity to drug. The most sensitive cell lines were colon and glioblastoma, and the most resistance were ovarian, breast and epithelioid sarcoma.
 ...
PMID:Camptothecin cytotoxic effects in vitro: dependency on exposure duration and dose. 757 68

Activity of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) is an important determinant of responsiveness of tumor cells to chloroethylnitrosoureas (CENUs), representative chemotherapeutic agents for primary malignant gliomas. In order to assess the real states of this repair protein in human malignant gliomas, we assayed AGT activity in surgically extirpated 42 malignant glioma samples and studied the distribution of the activity under certain clinical conditions. There were wide variations in AGT activity between individuals. No significant difference in AGT activity on average was seen either between glioblastoma and anaplastic astrocytoma, nor between primary and recurrent tumors. Among 42 malignant gliomas, 7 samples (16.7%) had low AGT activity less than 0.1 pmoles/mg protein. In the case of glioblastoma, tumors possessing higher AGT activity tended to be less responsive to post-operation remission-induction therapy including CENUs. The result of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) chemosensitivity assay by using the corresponding surgical specimens suggested a close relationship between cellular resistance to CENUs and AGT activity. It was found to be unlikely that a short term administration of CENUs had a significant effect on AGT activity of brain tumors in human body. We could detect a bit of definite evidences of the relevance of AGT to resistance to CENUs and need to conduct further investigations for other resistance factors.
 ...
PMID:O6-alkylguanine-DNA alkyltransferase activity of human malignant glioma and its clinical implications. 786 Nov 89

The monoclonal antibody Ki-67 recognizes a nuclear antigen expressed in the G1, S, G2, and M phase of the cell cycle and has been used extensively as an indicator of cellular proliferation in malignant gliomas, both in the laboratory and clinically. Recently, protein kinase C (PKC) inhibitors have been demonstrated to inhibit malignant glioma growth both in in vitro and in vivo. This study was undertaken to determine whether Ki-67 could function as an indicator of cellular proliferation rate after PKC inhibition in gliomas and to explore cell cycle specificity of such inhibition. Both established and low-passage malignant glioma cell lines have previously been shown to be sensitive to growth inhibition by the PKC inhibitors staurosporine and tamoxifen in vitro (IC50 in the nanomolar and micromolar ranges, respectively), as measured by cell numbers, [3H]thymidine uptake, and flow-cytometric DNA analysis. However, in the same cells that are inhibited by staurosporine and tamoxifen on these assays, and on the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay in the present study, the Ki-67 labeling index paradoxically increased in a dose-related manner with the same treatments, as measured by immunohistochemistry and confirmed by flow cytometry. For example, in established line U-87, a 20.5% decrease in thymidine uptake and a 28.5% decrease in absorbance on the MTT assay produced by tamoxifen at 1 microM was associated with an increase in Ki-67 labeling from 42% to 62%; staurosporine, which produces a 78.8% decrease in thymidine uptake in cell line A-172 at 10 nM, produced an increase in Ki-67 labeling from 19% to 32%. In this regard, Ki-67 labeling of glioblastoma tissue from a patient treated with high-dose tamoxifen yielded results within the range of 10% to 15% (consistent with values seen in untreated glioblastoma), despite tumor regression with treatment. The authors' interpretation of these results is that these PKC inhibitors are halting the cell cycle in the G1 phase or the G1-S transition (beyond G0 but before S-phase), resulting in a paradoxical increase in labeling while arresting growth. Two important implications from these observations are that Ki-67 is not a reliable indicator of cellular proliferation after treatment with PKC inhibitors and that these inhibitors used at the doses given above halt cell growth in a phase-specific manner.
 ...
PMID:Paradoxical elevation of Ki-67 labeling with protein kinase inhibition in malignant gliomas. 786 Dec 25

We have characterized two human glioblastoma cell lines, which were designated as YH cells and AM cells. The two cell lines maintained morphological appearance observed in the primary culture and immunohistochemically expressed glial fibrillary acidic protein (GFAP) and S-100 protein. Population doubling time for YH cells and AM cells indicated 30 hours and 25 hours, respectively, in an exponential phase of culture. Inoculation of AM cells into athymic nude mice formed large tumors at a high incidence. As with chemosensitivity to chloroethylnitrosourea, O6-methylguanine-DNA methyltransferase (MGMT) activity was measured in in vitro cultured cells as well as tumor specimens obtained at surgery. YH cells showed a high MGMT activity of 1196 fmol/mg and drug resistance to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. YH tumor specimens indicated an MGMT activity of 301 fmol/mg, which reflected poor effectiveness of ACNU chemotherapy in the clinical evaluation. AM cells had an extremely low MGMT activity of 16 fmol/mg and were vulnerable to ACNU. Original tumor specimens of AM cells however expressed a high value of 628 fmol/mg. Considering that ACNU chemotherapy was not effective in the both patients, an MGMT activity of original tumors related with responsiveness to ACNU. Discrepancy in an MGMT activity between the in vitro cell lines and the respective tumor specimens comes from selection of ACNU-sensitive cells or alteration in biological characteristics during long term culture. These results suggest that cell lines derived human brain tumors are useful targets for understanding the chemosensitivity of human malignant gliomas and for establishing a pertinent chemosensitivity test.
 ...
PMID:Characterization and chemosensitivity of two cell lines derived from human glioblastomas. 814 54

Acute intermittent porphyria (AIP) or precursor syndrome is a well described neuropathic clinical entity with incompletely known etiology. The most prominent biological abnormalities associated with this syndrome are elevations in serum and hepatic delta-aminolevulinic acid (ALA) and porphobilinogen (PBG). We determined the impact of ALA and PBG on human neuroblastoma and glioblastoma tumor cell survival as measured by the MTT assay. ALA proved to be cytotoxic in neuroblastoma cells, while PBG lacked cytotoxic effects. This cytotoxic effect of ALA could be enhanced by deferoxamine and diminished by heme, presumably through modulation of ALA synthesis. In conclusion, ALA excess may prove to be associated with the development of neuropathy in AIP.
 ...
PMID:delta-Aminolevulinic acid effects on neuronal and glial tumor cell lines. 827 91

Responses and susceptibility of 14 human glioblastoma cell lines to human natural tumor necrosis factor-alpha (TNF) were studied in vitro. Susceptibility of glioblastoma cells to TNF varied in experimental conditions applied. Most of glioblastoma cell lines were resistant to cytotoxic activity of TNF in a MTT assay at concentrations below 16 U/ml for 72 h exposure. However, TNF at higher dose, in prolonged exposure and against low density of target cells was antiproliferative for certain glioblastoma cultures. TNF exposure at 10 U/ml for 48 h suppressed DNA synthesis in 9 of 14 glioblastoma cultures, but increased in 3 cultures. In addition, colony forming assay showed anti-clonogenic activity of TNF in 5 of 6 glioblastoma cell lines tested. In spite of their low susceptibility to TNF, glioblastoma cells well responded to TNF stimulation at low dose (10 U/ml) for a short period in the absence of cell damage. Productions of Interleukin-6 (IL-6), IL-8-like activity, granulocyte-macrophage colony stimulating factor (GM-CSF), prostaglandin E2 (PGE2) and manganous superoxide dismutase (Mn-SOD) were enhanced or induced by the low-dose TNF stimulation. Mn-SOD, a protein protective against oxidative cell damage, was well induced in time- and dose-dependent manner, however did not correlate with TNF resistance. Whereas the levels of PGE2 in TNF-susceptible cell lines, H-4 and SF-188, were higher than those of other lines. In conclusion, most of glioblastoma cells are resistant to TNF cytotoxic effects, but highly responsive to TNF stimulation. Its effect on glioblastoma cells appears to modulate cell differentiation rather than to kill the cells.
 ...
PMID:Responses of human glioblastoma cells to human natural tumor necrosis factor-alpha: susceptibility, mechanism of resistance and cytokine production studies. 836 Jul 7

We have investigated the potential role of gastrin in the regulation of cell growth in human astrocytic tumors. To this end we have used synthetic analogs of gastrin and cholecystokinin (CCK) which behave as gastrin and/or CCK antagonists, e.g. compounds JMV-97, JMV-209 and JMV-179. Their effects on astrocytic tumor cell proliferation was investigated by the use of the colorimetric MTT assay. The in vitro biological models used in the present study included the SW1088, U87 and U373 astrocytic tumor cell lines. The results demonstrated marked influence of gastrin and CCK antagonists in the regulation of astrocytic tumor growth. This suggests that gastrin and/or CCK antagonists might be tested in experimental glioblastoma.
 ...
PMID:The influence of gastrin and/or cholecystokinin antagonists on the proliferation of three human astrocytic tumor cell lines. 892 4

Functional VIP/PACAP receptors were identified in the human glioblastoma cell line T98G, based on the relative potency of VIP, PACAP and PACAP-38 to stimulate adenylate cyclase activity. Analysis of the T98G cells mRNA by reverse transcription followed by a polymerase chain reaction (RT-PCR) demonstrated the expression of the mRNA coding for the VIP2 receptor subclass only. VIP, PACAP-27 and PACAP-38 were potent and efficIent inhibitors of cell proliferation, assessed by the colorimetric MTT assay. VIP, PACAP-27 and PACAP-38 also reduced the incorporation of 3H-thymidine in T98G cells, but did not significantly alter the percentage of cells present at each stage of the cell cycle. Thus, VIP and PACAP, probably acting through a VIP2 receptor subtype, decreased cell proliferation.
 ...
PMID:VIP and pituitary adenylate cyclase activating polypeptide (PACAP) have an antiproliferative effect on the T98G human glioblastoma cell line through interaction with VIP2 receptor. 892 13


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