Effects of dexamethasone and methylprednisolone on cell cultures of human glioblastomas

1971 ◽  
Vol 34 (3) ◽  
pp. 324-334 ◽  
Author(s):  
John Mealey ◽  
Tsu T. Chen ◽  
George P. Schanz
Keyword(s):  
Cell Cultures ◽  
Glioma Cells ◽  
Clinical Applications ◽  
Natural Rate ◽  
Content Type ◽  
Culture Growth ◽  
Different Origins ◽  
Dose Dependent ◽  
Fine Print

✓ Eight biopsied glioblastomas were propagated in vitro through multiple, serial cell cultures which were exposed to dexamethasone and methylprednisolone in concentrations ranging from 0.25 to 400 µg/ml. The higher concentrations of both steroids produced inhibition of culture growth and cytotoxic damage which appeared relatively nonspecific. Although the responses observed were dose-dependent, the sensitivity among glioma cultures of different origins varied. Of the two steroids, Methylprednisolone was more injurious to glioma cells in vitro and was cytolytic in doses of 400 µg/ml. Growth inhibition was demonstrated after a 1-day exposure to this corticoid, but this effect was usually transient at lower doses. Thereafter, surviving resistant cells resumed their natural rate of growth in the continued presence of the steroid as well as under standard conditions of culture. Potential clinical applications of the antineoplastic properties of corticosteroids against the gliomas are discussed, emphasizing the need to investigate additional, possibly more efficacious compounds.

Differential effects of vincristine and phenytoin on the proliferation, migration, and invasion of human glioma cell lines

1995 ◽  
Vol 82 (6) ◽  
pp. 1035-1043 ◽  
Author(s):  
Jörg-Christian Tonn ◽  
Hans Kristian Haugland ◽  
Jaakko Saraste ◽  
Klaus Roosen ◽  
Ole Didrik Laerum
Keyword(s):  
Cell Lines ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Content Type ◽  
Glioma Cell Lines ◽  
Dose Dependent ◽  
Fine Print

✓ The aim of this study was to investigate the antimigratory and antiinvasive potential of vincristine sulfate (VCR) on human glioma cells and to analyze whether phenytoin (5,5-diphenylhydantoin; DPH) might act synergistically with VCR. Vincristine affects the cytoplasmic microtubules; DPH has been reported to enhance VCR cytotoxicity in murine cells. In two human glioma cell lines, GaMG and D-37MG, we found VCR to reduce monolayer growth and colony formation in a dose-dependent fashion at concentrations of 10 ng/ml and above. Phenytoin increased the cytotoxic and cystostatic effects of VCR in monolayer cells but not in spheroids. Multicellular spheroids were used to investigate directional migration. A coculture system of GaMG and D-37MG spheroids with fetal rat brain aggregates was used to analyze and quantify tumor cell invasion. A dose-dependent inhibition of migration and invasion by VCR was observed in both cell lines without further enhancement by DPH. Immunofluorescence microscopy with antibodies against α-tubulin revealed dose-dependent morphological alterations in the microtubules when the cells were exposed to VCR but not after incubation with DPH. Based on the combination of standardized in vitro model systems currently in use and the present data, the authors strongly suggest that VCR inhibits migration and invasion of human glioma cells. This is not altered by DPH, which inhibits cell proliferation in combination with VCR.

Intra-arterial ACNU therapy for malignant brain tumors

1983 ◽  
Vol 59 (3) ◽  
pp. 424-430 ◽  
Author(s):  
Junkoh Yamashita ◽  
Hajime Handa ◽  
Yasuhiko Tokuriki ◽  
Young Soo Ha ◽  
Shin-Ichi Otsuka ◽  
...  
Keyword(s):  
Survival Time ◽  
Postoperative Radiotherapy ◽  
Glioma Cells ◽  
Mantel Test ◽  
Survival Times ◽  
Content Type ◽  
The Difference ◽  
Intracarotid Administration ◽  
Fine Print

✓ The authors examined the growth rate of mouse 203 glioma cells in vitro and found it to be markedly inhibited after exposure to ACNU for 5 minutes at a drug concentration of 100 µg/ml. Rats that had undergone intracranial implantation of T1 neurogenic tumor were treated by 5 mg/kg of ACNU administered either intravenously or intra-arterially. The median survival times for the control animals and the animals undergoing intravenous or intracarotid administration of ACNU were 23, 29, and 46 days, respectively. The difference in survival time between the intravenous and intracarotid administration groups was statistically significant (p < 0.01) when examined by the Cox-Mantel test. In a clinical trial, 17 patients with glioblastoma were treated by ACNU, eight intravenously and nine by the intra-arterial route. The drug was given in doses of 2 to 3 mg/kg at least twice before and twice after a course of postoperative radiotherapy. Intra-arterial administration was performed over a period of 5 minutes under local anesthesia. The median postoperative survival time for the patients in the intra-arterial group was 12.5 months, compared with 9.0 months for those in the intravenous group. The survival rate for the intra-arterial group was slightly higher, although statistically not significant, probably because the number of cases was small. The degree of thrombocytopenia due to ACNU tended to be less marked in the intra-arterially treated patients. The theoretical advantages of the intra-arterial administration of ACNU are discussed.

In vitro photoradiation therapy of the rat 9L gliosarcoma

1986 ◽  
Vol 64 (5) ◽  
pp. 775-779 ◽  
Author(s):  
Douglas Hamilton ◽  
John D. S. McKean ◽  
John Tulip ◽  
Donald Boisvert ◽  
Judy Cummins
Keyword(s):  
Trypan Blue ◽  
Glioma Cells ◽  
Laser Source ◽  
Trypan Blue Exclusion ◽  
Content Type ◽  
9L Gliosarcoma ◽  
Trypan Blue Exclusion Test ◽  
9L Glioma ◽  
Fine Print

✓ The authors have investigated various factors involved in the photoradiation treatment of 9L glioma cells. The cells were grown in tissue culture and exposed to light from a laser source that allowed accurate quantitation of the light energy. Cell death was determined following treatment using the trypan blue exclusion test. It was shown that the treatment is very wavelength-dependent following the absorption spectrum of hematoporphyrin derivative (HPD). The absorption peaks in the lower part of the spectrum are more efficient than those of higher wavelengths. Photoradiation therapy is more effective the higher the concentration of HPD. Intensity of light is a very important factor in calculating the total dose of light necessary for this treatment.

Antiproliferative effect of trapidil, a platelet-derived growth factor antagonist, on a glioma cell line in vitro

1990 ◽  
Vol 73 (3) ◽  
pp. 436-440 ◽  
Author(s):  
Jun-ichi Kuratsu ◽  
Yukitaka Ushio
Keyword(s):  
Growth Factor ◽  
Cell Lines ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Inhibitory Effect ◽  
Platelet Derived Growth Factor ◽  
Content Type ◽  
Glioma Cell Lines ◽  
Fine Print

✓ Platelet-derived growth factor (PDGF) is produced by glioma cells. However, there is heterogeneity among glioma cell lines in the production of PDGF. It has been demonstrated that U251MG cells produce a PDGF-like molecule while U105MG cells do not. Trapidil, a specific antagonist of PDGF, competes for receptor binding with PDGF. Therefore, the inhibitory effect of trapidil on the proliferation of glioma cells was investigated in vitro using two glioma cell lines. At 100 µg/ml, trapidil significantly inhibited the proliferation of U251MG cells (which produce the PDGF-like molecule). At the same trapidil concentration, the proliferation of U105MG cells (which do not produce the PDGF-like molecule) was not inhibited. The inhibitory effect of trapidil was remarkable on Days 3 and 4 of culture. After 4 days of incubation, the proliferation of U251MG cells was 46% of the control preparation. Trapidil enhanced the antitumor effect of 3-((4-amino-2-methyl-5-pyrimidinyl)ethyl)-1-(2-chloroethyl)-1-nitro-sourea (ACNU) against U251MG cells. The enhancing effect was highest on Days 4 and 6 of culture. After 6 days of incubation in the presence of 100 µg/ml trapidil and 1 µg/ml ACNU, the proliferation of U251MG cells was 18% of the control preparation. These findings suggest that trapidil interrupts the autocrine loop at the PDGF and PDGF-receptor level and that combination therapy with trapidil and ACNU may be useful in the treatment of glioma.

Modulation of phorbol ester—induced regulation of matrix metalloproteinases and tissue inhibitors of metalloproteinases by SB203580, a specific inhibitor of p38 mitogen-activated protein kinase

2002 ◽  
Vol 97 (1) ◽  
pp. 112-118 ◽  
Author(s):  
Myung-Jin Park ◽  
In-Chul Park ◽  
Jin-Heang Hur ◽  
Mi-Suk Kim ◽  
Hyung-Chan Lee ◽  
...  
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Specific Inhibitor ◽  
Glioma Cells ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Boyden Chamber ◽  
Content Type ◽  
In Vitro Invasion ◽  
Fine Print

Object. Expression of matrix metalloproteinases (MMPs) has been postulated to play a central role in brain tumor invasion; however, its underlying mechanism is not yet fully understood. In the present study, by assessing the effect of a specific p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, on the secretion of MMPs and in vitro invasion of various glioma cells, the authors attempt to define the role of the p38 MAPK pathway in the regulation of MMPs and tissue inhibitors of metalloproteinases (TIMPs) activated by phorbol ester (phorbol-12-myristate-13-acetate [PMA]) in the D54 human glioblastoma cell line. Methods. The activation of MAPKs was determined using Western blot analysis after addition of phospho-specific antibodies against these kinases, the status of MMPs and TIMPs was analyzed using gelatin zymography and Western blot analysis, and the invasion rate of D54 cells and other glioma cells was analyzed using a modified Boyden chamber assay. Treatment of D54 cells with PMA activated two distinct MAPKs, extracellular signal-regulated kinase (ERK) 1/2 and p38 MAPK, but not c-Jun N-terminal kinase/stress-activated protein kinase. Induction of MMP-9 production and MMP-2 activation by PMA were blocked by SB203580, a specific inhibitor of p38 MAPK, but not by PD98059, a specific inhibitor of ERK 1/2. In addition, PMA-induced downregulation of TIMP-1 and TIMP-2 secretion and upregulation of the membrane type 1 MMP, a major activator of MMP-2 on the cell surface, were reversed by SB203580 in these cells; the PMA-induced increase of invasion in vitro decreased when SB203580 was added to the top compartment of a modified Boyden chamber; and the inhibitor also reduced the MMP secretion and PMA-induced in vitro invasion in various glioma cell lines. Conclusions. These results indicate that activation of p38 MAPK by PMA plays a central role in the regulation of MMPs and TIMPs in D54 cells, which has a major influence in tumor invasion and metastasis. Furthermore, inhibition of p38 MAPK by SB203580 blocked the secretion of MMPs and in vitro invasion of various glioma cells, underscoring a possible role of p38 MAPK inhibitors as antiinvasive and/or antimetastatic agents of malignant gliomas.

Inhibitory effect of antisense epidermal growth factor receptor RNA on the proliferation of rat C6 glioma cells in vitro and in vivo

2000 ◽  
Vol 92 (1) ◽  
pp. 132-139 ◽  
Author(s):  
Peiyu Pu ◽  
Xuwen Liu ◽  
Aixue Liu ◽  
Jianling Cui ◽  
Yunting Zhang
Keyword(s):  
Survival Time ◽  
Glioma Cells ◽  
C6 Glioma ◽  
C6 Glioma Cells ◽  
C6 Cells ◽  
Content Type ◽  
Proliferation Activity ◽  
Fine Print

Object. The goal of this study was to evaluate the effect of antisense epidermal growth factor receptor (EGFR) RNA on the growth of rat glioma cells in vitro and in vivo and to determine the feasibility of targeting the EGFR gene for gene therapy in gliomas.Methods. Antisense EGFR complementary (c)DNA was transfected into C6 glioma cells by using lipofectamine. In vitro studies, Southern and Northern blot analyses, in situ hybridization, and immunohistochemical staining were designed to examine the integration and expression of antisense EGFR constructs. The 3′(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay and the average number of argyrophilic nuclear organizer regions (Ag-NORs) were used to evaluate cell proliferation, whereas the terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method and microscopy were used to observe cell apoptosis. As part of the in vivo studies, parental C6 cells and C6 cells transfected with EGFR antisense cDNA were implanted stereotactically into the right caudate nucleus of Wistar rats (C6-injected animals and transfected C6-injected animals). Rats with well-established cerebral C6 glioma foci were treated intratumorally with either antisense EGFR cDNA or empty-vector DNA by using lipofectamine (treated-C6 and control treated group). The general behavior and survival of the rats, findings on magnetic resonance images of their brains, histopathological changes, proliferation activity, and apoptosis of the cerebral gliomas in each group of rats were examined.Exogenous antisense EGFR cDNA was integrated into the genome of C6 cells and expressed. In clones with a high expression of the antisense construct, there was a dramatic decrease in endogenous EGFR messenger RNA and protein levels, reduced proliferation activity, and induction of apoptosis in vitro. The mean survival time of rats injected with C6 cells was 17.3 days. The mean survival time of rats injected with C6 cells followed by treatment with empty vector in lipofectamine was 15.4 days. Survival time was significantly prolonged in 100% of the rats injected with antisense-transfected C6 cells and in two thirds of the rats injected with C6 cells followed by antisense EGFR cDNA. Magnetic resonance imaging revealed distinct cerebral tumor foci in C6-injected rats and in control rats of the treated group, but none were found in the rats injected with transfected C6 cells. Furthermore, tumor foci disappeared completely in C6-injected rats treated with antisense EGFR cDNA. The cerebral gliomas of the rats treated by injection of antisense EGFR RNA were characterized by reduced proliferation activity and the induction of apoptosis.Conclusions. The results of this study indicate that EGFR plays an important role in the genesis of malignant gliomas. It may, therefore, be an effective target of antisense gene therapy in patients with gliomas.

Enhancement of macrophage cytotoxicity against murine gliomas by interferon beta increase in nitric oxide production in response to glioma-derived soluble factors

2002 ◽  
Vol 97 (3) ◽  
pp. 619-626 ◽  
Author(s):  
Tomohiro Kito ◽  
Etsushi Kuroda ◽  
Akira Yokota ◽  
Uki Yamashita
Keyword(s):  
Nitric Oxide ◽  
Cytotoxic Activity ◽  
Glioma Cells ◽  
Cell Contact ◽  
No Production ◽  
Soluble Factors ◽  
Content Type ◽  
Culture Supernatants ◽  
Fine Print

Object. In previous studies interferon-β (IFNβ) has been shown to suppress tumor growth. In this report, the antitumor effect of macrophages stimulated with IFNβ is investigated in murine gliomas in vitro. Methods. The authors examined the cytotoxic activity of IFNβ-stimulated peritoneal macrophages in glioma cells labeled with [3H]thymidine. The addition of IFNβ enhanced cytotoxic activity in gliomas as well as the nitric oxide (NO) production of macrophages in cocultures. Addition of NG-monomethyl-l-arginine (l-NMMA) and l-N6-(1-iminoethyl)-lysine, but not d-NMMA (an inactive analog of l-NMMA), blocked this cytotoxic activity. The addition of IFNβ had no direct effect on the growth of glioma cells. Because NO was not produced from macrophages treated with IFNβ alone and IFNβ-induced cytotoxic activity did not need cell-to-cell contact, the authors suspected that gliomas produce some soluble factors that act as cofactors for IFNβ-induced cytotoxic activity. Macrophages stimulated with IFNβ in the presence of glioma culture supernatants showed higher cytotoxicity against glioma cells than macrophages stimulated with IFNβ alone. Furthermore, NO was markedly produced by IFNβ-stimulated macrophages in the presence of glial culture supernatants. Conclusions. These data indicate that the antiglioma activity of IFNβ through macrophages is due to NO produced by macrophages and that glioma-derived soluble factors play a role as an essential cofactor in this activity.

Inhibition of growth of established human glioma cell lines by modulators of the protein kinase-C system

1990 ◽  
Vol 73 (4) ◽  
pp. 594-600 ◽  
Author(s):  
William T. Couldwell ◽  
Jack P. Antel ◽  
Michael L. J. Apuzzo ◽  
Voon Wee Yong
Keyword(s):  
Glioma Cell ◽  
Glioma Cells ◽  
Thymidine Uptake ◽  
Human Glioma ◽  
Content Type ◽  
Inhibition Of Growth ◽  
Kinase C ◽  
Glioma Cell Lines ◽  
Fine Print

✓ The protein kinase-C (PKC) second messenger system contributes to regulation of cell growth and differentiation. This study was undertaken to examine the effects of modulators of the PKC enzyme system on the state of differentiation and proliferation rates of human gliomas in vitro. The administration of the PKC-activating phorbol esters 4-beta-phorbol-12,13-dibutyrate (PDB) and phorbol-12-myristate-13-acetate (PMA) resulted in a dose-related inhibition of growth of human glioma cell lines in vitro as measured by 3H-thymidine uptake. The synthetic nonphorbol PKC activator (SC-9) produced an even more pronounced decrease of 3H-thymidine uptake. Diacylglycerol, an endogenous activator of the system, applied externally, transiently decreased the proliferation, in concordance with its short-lived existence in vivo. Conversely, the administration of 4-alpha-phorbol-12,13-didecanoate (α-PDD), a phorbol ester that binds but does not activate the enzyme, had no effect on the proliferation rate. At the dosages that maximally decreased proliferation, there was no evidence of direct glioma cell lysis induced by these agents as measured by a chromium-release assay. Immunocytochemical analysis and cytofluorometric measurement of glial fibrillary acidic protein (GFAP) staining in the treated cultures revealed an increase in GFAP staining over control cultures. In contrast to the response of glioma cells, nonmalignant human adult astrocytes treated with the PKC activators responded by increasing their proliferation rate. The authors postulate that the diametrically opposed effects of PKC activators on nonmalignant astrocytes versus glioma growth may be due to a high intrinsic PKC activity in glioma cells, with resultant down-regulation of enzyme activity following the administration of the pharmacological activators.

In vitro studies of cytokine-mediated interactions between malignant glioma and autologous peripheral blood mononuclear cells

1994 ◽  
Vol 81 (4) ◽  
pp. 579-586 ◽  
Author(s):  
Piotr Jachimczak ◽  
Udo Schwulera ◽  
Ulrich Bogdahn
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Mononuclear Cells ◽  
Glioma Cells ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Blood Mononuclear Cells ◽  
Glioma Cell Proliferation ◽  
Fine Print

✓ The humoral interactions between three malignant glioma early-passage cell cultures and in vitro interleukin (IL)-1α- and IL-2-activated autologous peripheral blood mononuclear cells (PBMC's) were investigated, employing standard and modified (separated by permeable membranes) mixed lymphocyte tumor cell (MLTC) cultures. In modified MLTC's, glioma cells clearly inhibit proliferation of PBMC's (up to 60%), whereas lymphokine-activated PBMC's enhance glioma cell growth up to 12-fold, as determined by 3H-thymidine incorporation assays. Glioma cells produce both stimulatory (IL-6) and inhibitory proteins (transforming growth factor-β) for PBMC's. Lymphokine-activated PBMC's secrete IL-1α, IL-2, IL-4, IL-6, interferon-γ, and tumor necrosis factor-α, which may modulate glioma cell proliferation. None of these cytokines stimulated glioma cells as intensely as modified MLTC systems. These observations indicate that in vitro lymphokine-activated PBMC's, although suppressed by humoral glioma-derived factors, may enhance glioma cell proliferation with soluble factors secreted into the culture medium. The authors conclude that glioma-lymphocyte growth regulatory networks include stimulatory and inhibitory factors from both cell populations, which may modulate tumor progression. These observations may have relevance for adoptive immunotherapy in patients with gliomas.

scholarly journals In VitroActivities of Hexaazatrinaphthylenes against Leishmania spp.

2015 ◽  
Vol 59 (5) ◽  
pp. 2867-2874 ◽  
Author(s):  
Atteneri López-Arencibia ◽  
Daniel García-Velázquez ◽  
Carmen M. Martín-Navarro ◽  
Ines Sifaoui ◽  
María Reyes-Batlle ◽  
...  
Keyword(s):  
Therapeutic Agents ◽  
Content Type ◽  
Inhibition Effect ◽  
Intracellular Amastigotes ◽  
Dependent Inhibition ◽  
Leishmania Spp ◽  
Dose Dependent Inhibition ◽  
Dose Dependent ◽  
Potential Use

ABSTRACTThein vitroactivity of a novel group of compounds, hexaazatrinaphthylene derivatives, against two species ofLeishmaniais described in this study. These compounds showed a significant dose-dependent inhibition effect on the proliferation of the parasites, with 50% inhibitory concentrations (IC50s) ranging from 1.23 to 25.05 μM against the promastigote stage and 0.5 to 0.7 μM against intracellular amastigotes. Also, a cytotoxicity assay was carried out to in order to evaluate the possible toxic effects of these compounds. Moreover, different assays were performed to determine the type of cell death induced after incubation with these compounds. The obtained results highlight the potential use of hexaazatrinaphthylene derivatives againstLeishmaniaspecies, and further studies should be undertaken to establish them as novel leishmanicidal therapeutic agents.

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