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)

In the search for cytokines whose antiproliferative action could be enhanced by combination with dipyridamole, 2,6-bis(diethanolamino)-4,8-dipiperidinopyrimido[5,4-d]pyrim idine, the combination of tumor necrosis factor-alpha (TNF-alpha) with this agent was evaluated in various human tumor cell lines. Inhibition of the proliferation of human melanoma cell lines MM-1CB and HMV-1 by TNF-alpha (1-10(2) U/ml) was enhanced in culture dishes by combination treatment with dipyridamole (0.1-10 microM). The enhancement effect was also detected in other tumor cell lines: T98 (glioma), SCC-1CB (squamous cell carcinoma), HAC-2 (ovarian clear-cell carcinoma), HLE (hepatoma), HEC-1 (endometrial adenocarcinoma) and HOC-21 (ovarian serous cystadenocarcinoma). The incorporation of [14C]amino acids and [3H]uridine into acid-insoluble cell materials in the combination-treated cells was not significantly different from that in cells treated with TNF-alpha or dipyridamole. However, the incorporation of [3H]thymidine was specifically inhibited in all cell lines examined after more than 12 h of the TNF-alpha and dipyridamole combination treatment, although neither agent alone inhibited this incorporation. On the other hand, the growth of tumors induced by the injection of MM-1CB and HMV-1 cells into nude mice was more markedly inhibited by the subcutaneous administration of TNF-alpha in combination with orally administered dipyridamole than by either agent alone. The results presented suggested that dipyridamole is beneficial in assuring the effectiveness of anti-cancer cytokine therapy.
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PMID:Dipyridamole combined with tumor necrosis factor-alpha enhances inhibition of proliferation in human tumor cell lines. 755

Cytokines exert receptor-mediated control over glia. Up-regulation of receptor expression of cytokine production corresponds with the acquisition of a neoplastic phenotype. A modified radial dish assay was used to determine whether in vitro locomotion of glioma cells is modified by the epidermal growth factor, the basic fibroblast growth factor, the bb dimer of platelet-derived growth factor, the nerve growth factor, or the tumor necrosis factor alpha. Human glioma cells were plated in the center of a petri dish with one of these cytokines in 0.5 ml agar (50 ng/ml if the cytokine was distributed evenly throughout the dish) at one edge, and 0.5 ml plain agar at the opposite edge. After 24 hours, a central zone of cells was established; the agar was gelatinized. Feeding medium was added to the dish, and slow elution from the agar established a cytokine gradient. Cell counts were performed daily over 6 to 10 days at predetermined distances on both sides of the central zone to assess directional cellular movement with respect to the cytokine gradient and the plain agar. The epidermal growth factor caused continuous chemoattraction, whereas the tumor necrosis factor alpha caused slight chemorepulsion for 24 to 48 hours, followed by strong chemoattraction. The bb dimer of platelet-derived growth factor, the basic fibroblast growth factor, and the nerve growth factor all maintained chemorepulsion over the entire 6 to 10 days. Therefore, the cytokines did affect glioma cell motility in vitro, and the modified radial dish assay used in this study provided a useful in vitro model for assessing the impact of the cytokines on glioma cell locomotion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modification of human glioma locomotion in vitro by cytokines EGF, bFGF, PDGFbb, NGF, and TNF alpha. 764 98

The ability of a mannoprotein antigen from Candida albicans (MP) or interleukin-2 (IL-2) to induce cytokines in cultures of peripheral blood mononuclear cells (PBMC) of glioma patients and healthy controls was evaluated by mRNA expression and by protein secretion. The subjects studied were all responsive to both MP and IL-2, as assayed by lymphoproliferation of PBMC cultures. In control subjects, MP and IL-2 were strong inducers of IFN-gamma, IL-1 beta, TNF-alpha, and GM-CSF mRNA expression, but only MP was able to induce considerable levels of IL-6 and IL-2 mRNA expression. In MP-activated PBMC from glioma subjects, a highly defective IFN-gamma, together with a significant reduction in TNF-alpha and GM-CSF mRNA expression, was observed. This impairment was paralleled by a decreased accumulation of IL-6 and IL-2 mRNA. The pattern of cytokine mRNAs in IL-2-activated PBMC of glioma patients confirmed the impairment of IFN-gamma mRNA expression paralleled by a reduction in IL-6, TNF-alpha and GM-CSF mRNA, compared with healthy subjects. Coherently, in PBMC cultures from glioma patients, there was a clear-cut decrease in the secretion of IL-6 and TNF-alpha and especially of IFN-gamma compared with healthy controls. No or very low levels of IL-4, IL-10, and TGF-beta 2 mRNA expression were detected in PBMC cultures of both glioma and control populations, irrespective of the activation conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Defective expression of interferon-gamma, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, and interleukin-6 in activated peripheral blood lymphocytes from glioma patients. 764 44

Expression of the cytokine genes in human glioma cell lines and specimens was studied. Primers for 7 different human cytokine, IL-1 beta, IL-6, IL-8, GM-CSF, TGF-beta 1, TNF-alpha and IFN-gamma were used to analyze messenger RNA transcripts by polymerase chain reaction (PCR). Messenger RNA encoding for IL-1 beta, IL-6, IL-8, GM-CSF and TGF-beta 1 was found to be expressed in some of glioma cell lines. And those showed a proliferative response to IL-1 beta. IL-8 mRNA was found in 2 of 5 low grade gliomas, in 8 of 9 high grade gliomas. TGF-beta 1 mRNA was found in all gliomas, in 1 of 2 normal brains. IL-1 beta mRNA was only found in normal brains. TNF-alpha and IFN-gamma were not found in glioma cell lines and specimens. IL-8 mRNA was apt to be found more frequently among high grade glioma specimens.
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PMID:Cytokine gene expression on glioma cell lines and specimens. 769 19

Two aspects of cytokine therapy of intracerebral tumors are considered in this study: modulation of tumor growth in vivo and central nervous system toxicity. Coimplantation of RG-2 glioma cells and retroviral vector producer cell lines was performed to provide a local source of interleukin-2 (IL-2) or IFN-gamma within the tumor and coinitiate an antitumor immune response. We demonstrated that local intratumoral production of IL-2 and IFN-gamma generates a cell-mediated antitumor response in vivo. This response was manifest as a diffuse infiltration of monocytes/macrophages, CD4+ and CD8+ T cells, and activation of microglial OX42+ cells in intracerebral RG2 tumors. The cell-mediated antitumor immune response resulted in the early suppression of intracranial and subcutaneous tumor growth, but the effect was not sustained and there were no tumor regressions. The absence of increased survival of animals with intracranial tumors is explained in part by the severe central nervous system toxicity caused by local production of IL-2 and IFN-gamma. Central nervous system toxicity induced blood-brain barrier disruption, vasogenic brain edema, and dislocation of the brain midline structures, as observed by dynamic magnetic resonance imaging and direct measurements of tissue water content. The clinical application of IL-2 and IFN-gamma gene transfer therapy for intracerebral tumors must consider the potential for severe vasogenic brain edema associated with intracerebral production of these cytokines.
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PMID:RG-2 glioma growth attenuation and severe brain edema caused by local production of interleukin-2 and interferon-gamma. 772 57

The genes for interleukin (IL)-2, interferon (IFN)-gamma, or both IL-2 and IFN-gamma were introduced into a mouse fibroblast cell line (LM) expressing defined major histocompatibility complex determinants (H-2k). The cytokine-secreting cells were then co-transplanted with the Gl261 murine glioma cell line (H-2b) into syngeneic C57BL/6 mice that differed at the major histocompatibility complex from the cytokine-secreting cells. The period of survival of mice with glioma treated with IL-2- or IL-2/IFN-gamma-secreting allogeneic cells was significantly prolonged (P < 0.025) relative to the survival of mice receiving equivalent numbers of tumor cells alone or mice with glioma treated with nonsecreting fibroblast (LM) cells. Gliomas in the treated mice had an extensive lymphocytic cell infiltrate. Using a 51Cr release assay, the specific release of isotope from labeled Gl261 cells co-incubated with spleen from mice injected with the glioma cells and IL-2-secreting fibroblasts was higher (P < 0.001) than the release from glioma cells co-incubated with spleen cells from nonimmunized mice. Significantly higher levels of release (P < 0.005) were found in the group immunized with fibroblasts secreting both IL-2 and IFN-gamma. Based upon the effect of monoclonal antibodies for T-cell subsets on the antiglioma response, the immunity was mediated predominantly by natural killer/lymphokine-activated killer cells.
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PMID:Fibroblasts genetically engineered to secrete cytokines suppress tumor growth and induce antitumor immunity to a murine glioma in vivo. 775 55

We have been devoting our efforts to develop the useful liposomes that have high potentials of gene transfer and we aim human gene therapy for malignant glioma with cytokine genes. In our previous study, we prepared our original reverse-phase evaporation vesicles (REV) by an improved procedure of reverse-phase evaporation method. However, this procedure was very complicate. In this paper, a simple procedure for the preparation of cationic multilamellar vesicles (MLV) was introduced, and efficient expression and growth-inhibitory effect of MLV with entrapped human interferon-beta gene to glioma cells was comparable to that obtained with REV. Considering the present experiments, MLV seem to be more preferable for clinical application.
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PMID:Efficient transfection of human interferon-beta gene to human glioma cells by means of cationic multilamellar liposomes coupled with a monoclonal antibody [corrected]. 780 78

Interleukin 1 (IL-1) has been reported to act as a radioprotector in vivo. Data from our laboratory and from other investigators suggest that glioma cell lines can produce bioactive cytokines including IL-1 and also express IL-1 receptors. In view of the putative radioprotective effect of this cytokine, we have examined the in vitro radiosensitivity of three human glioma cell lines with widely varying levels of endogenous IL-1 beta. The data reveal that when irradiated (2 Gy/min) as confluent cultures (conditions optimal for differential IL-1 beta expression), and plated for colony formation after postirradiation holding, cell survival was not correlated with level of IL-1 beta mRNA expression in the two IL-1-expressing cell lines. However, this was not correlated with a further reduction in radiosensitivity. These data indicate that IL-1 beta does not act as an endogenous radioprotector in these cells under these experimental conditions.
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PMID:Variable expression of IL-1 beta has minimal effect on the radiation sensitivity of three human glioma cell lines. 781 77

Interleukin 10 (IL-10) was initially discovered on the basis of its ability to suppress cytokine synthesis. Additionally, it can exert immunosuppressive effects on a variety of cell types. Because patients with malignant gliomas present with a general impairment of the immune system, we investigated IL-10 expression in the glioma tissue. Because expression of IL-10 and IL-6 is associated in hematopoietic cells and IL-6 can act as an autocrine growth stimulator for glioblastoma cell lines, we looked in addition for a relationship between IL-10 and IL-6 expression. Using a quantitative reverse transcriptase polymerase chain reaction, IL-10 and IL-6 mRNA levels were determined in 37 glial tumors of different grades including 2 recurrencies, 3 specimens from normal brain tissue, and 3 glioblastoma cell lines. Expression of IL-10 mRNA was demonstrable in all tumors as well as in normal brain. High grade tumors and recurrent cases expressed significantly higher amounts of IL-10-specific mRNA compared with low grade tumors, whereas 2 of 3 cell lines showed only weak constitutive expression, mRNA for IL-6 was found in 86.5% of all gliomas with a correlation concerning the expression levels for both cytokines in 69% of gliomas. We suggest that IL-10 may contribute to the progression of astrocytomas by suppressing the patient's immune response, whereas IL-6 provides an additional growth advantage.
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PMID:Messenger RNA expression of the immunosuppressive cytokine IL-10 in human gliomas. 785 43

Little information exists regarding which glioma cells are able to escape immune system detection and progress within the host. In order to elucidate some of the mediators which facilitate the growth and spread of glioma cells, the expression of cytokines, TNF-alpha, IL-6, gamma-IFN, IL-10, and GM-CSF, within 12 human glioma specimens was investigated by the polymerase chain reaction. The twelve patients with malignant glioma were categorized into a localized (n = 4) and an invasive glioma (n = 8) groups, mostly glioblastoma multiforme, based upon the CT and MRI scans. We examined the correlation between specific cytokine gene expression and the clinical category of each patient. The results showed that while IL-10 mRNA transcripts were expressed in most of the tumors from the invasive glioma group (7/8), they were not expressed in tumors from the localized group. On the other hand, gamma-IFN gene expression was more frequent in tumors from the localized group (3/4 vs 1/8 from the invasive group). The mRNA transcripts of IL-6 and GM-CSF were more frequently expressed in tumors from the localized group. No consistent pattern was seen in TNF-alpha gene expression between the two groups. Among the five cytokines studied, IL-10 mRNA was selectively expressed within invasive gliomas compared to less malignant, localized glioma group. Our results demonstrate specific cytokine mRNA profiles in glioma patients, which might have prognostic significance for immunotherapy.
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PMID:Selective expression of interleukin-10 gene within glioblastoma multiforme. 795 24


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