Antitumor effects of polysorbate-80 coated gemcitabine polybutylcyanoacrylate nanoparticles in vitro and its pharmacodynamics in vivo on C6 glioma cells of a brain tumor model

2009 ◽  
Vol 1261 ◽  
pp. 91-99 ◽  
Author(s):  
Chun-Xia Wang ◽  
Le-Song Huang ◽  
Lian-Bing Hou ◽  
Liang Jiang ◽  
Zhi-Ting Yan ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Glioma Cells ◽  
Tumor Model ◽  
C6 Glioma ◽  
C6 Glioma Cells ◽  
Polysorbate 80 ◽  
Antitumor Effects ◽  
Brain Tumor Model

Radiosensitivity of glioma to Gamma Knife treatment enhanced in vitro and in vivo by RNA interfering Ku70 that is mediated by a recombinant adenovirus

2010 ◽  
Vol 113 (Special_Supplement) ◽  
pp. 228-235 ◽  
Author(s):  
Qiang Jia ◽  
Yanhe Li ◽  
Desheng Xu ◽  
Zhenjiang Li ◽  
Zhiyuan Zhang ◽  
...  
Keyword(s):  
Western Blot ◽  
Gamma Knife ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Glioma Cells ◽  
C6 Glioma ◽  
C6 Glioma Cells ◽  
C6 Cells

Object The authors sought to evaluate modification of the radiation response of C6 glioma cells in vitro and in vivo by inhibiting the expression of Ku70. To do so they investigated the effect of gene transfer involving a recombinant replication-defective adenovirus containing Ku70 short hairpin RNA (Ad-Ku70shRNA) combined with Gamma Knife treatment (GKT). Methods First, Ad-Ku70shRNA was transfected into C6 glioma cells and the expression of Ku70 was measured using Western blot analysis. In vitro, phenotypical changes in C6 cells, including proliferation, cell cycle modification, invasion ability, and apoptosis were evaluated using the MTT (3′(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) assay, Western blot analysis, and cell flow cytometry. In vivo, parental C6 cells transfected with Ad-Ku70shRNA were implanted stereotactically into the right caudate nucleus in Sprague-Dawley rats. After GKS, apoptosis was analyzed using the TUNEL (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling) method. The inhibitory effects on growth and invasion that were induced by expression of proliferating cell nuclear antigen and matrix metalloproteinase–9 were determined using immunohistochemical analyses. Results The expression of Ku70 was clearly inhibited in C6 cells after transfection with Ad-Ku70shRNA. In vitro following transfection, the C6 cells showed improved responses to GKT, including suppression of proliferation and invasion as well as an increased apoptosis index. In vivo following transfection of Ad-Ku70shRNA, the therapeutic efficacy of GKT in rats with C6 gliomas was greatly enhanced and survival times in these animals were prolonged. Conclusions Our data support the potential for downregulation of Ku70 expression in enhancing the radiosensitivity of gliomas. The findings of our study indicate that targeted gene therapy–mediated inactivation of Ku70 may represent a promising strategy in improving the radioresponsiveness of gliomas to GKT.

Wild Type p53 Gene Sensitizes Rat C6 Glioma Cells to HSV-TK/ACV Treatment In Vitro and In Vivo

2010 ◽  
Vol 16 (4) ◽  
pp. 509-514 ◽  
Author(s):  
Qiang Huang ◽  
Zhibo Xia ◽  
Yongping You ◽  
Peiyu Pu
Keyword(s):  
Glioma Cells ◽  
P53 Gene ◽  
C6 Glioma ◽  
C6 Glioma Cells ◽  
Wild Type ◽  
Wild Type P53 ◽  
Rat C6 Glioma

Effects of Gamma Knife surgery on C6 glioma in combination with adenoviral p53 in vitro and in vivo

2006 ◽  
Vol 105 (Supplement) ◽  
pp. 208-213 ◽  
Author(s):  
Desheng Xu ◽  
Qiang Jia ◽  
Yanhe Li ◽  
Chunsheng Kang ◽  
Peiyu Pu
Keyword(s):  
Glioma Cells ◽  
P53 Gene ◽  
Treated Group ◽  
C6 Glioma ◽  
C6 Glioma Cells ◽  
Survival Duration ◽  
Wild Type ◽  
Wild Type P53

ObjectThe authors sought to study the combined potential of wild-type p53 gene transfer and Gamma Knife surgery (GKS) for the treatment of glioblastomas multiforme. Modification of the radiation response in C6 glioma cells in vitro and in vivo by the wild-type p53 gene was investigated.MethodsStable expression of wild-type p53 in C6 cells was achieved by transduction of the cells with adenoviral p53. Two days later, some cells were treated with GKS. Forty-eight hours after irradiation, the comparative survival rate was assessed by monotetrazolium (MTT) assays. Treated and control C6 glioma cells (4 × 103 per well) were plated into a 96-well plate in octuplicate and tested every 24 hours. Meanwhile, immunohistopathological examination of proliferating cell nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate (TUNEL) assays were performed. The MTT assays indicated the p53, GKS, and combined treated cells proliferated at a significantly lower rate than those of the control group (p < 0.01, Days 2–6) and the positive fraction of PCNA in p53-treated group and GKS-treated group was 70.18 ± 3.61 and 50.71 ± 2.61, respectively, whereas the percentage in the combined group was 30.68 ± 1.49 (p < 0.01).Fifty-six male Sprague–Dawley rats were anesthetized and inoculated with 106 cultured C6 glioma cells into the cerebrum. Forty-eight hours after transduction with adenoviral p53, some rats underwent GKS. A margin dose of 15 Gy was delivered to the 50% isodose line. Two days later, six rats in each group were killed. Their brains were removed and paraffin-embedded section were prepared for immunohistopathological examination and TUNEL assays. The remaining rats were observed for the duration of the survival period. The survival curve indicated that a modest but significant enhancement of survival duration was seen in the p53-treated or GKS alone groups, whereas a more marked and highly significant enhancement of survival duration was achieved when these two treatment modalities were combined. When PCNA expression was downregulated, apoptotic cells become obvious after TUNEL staining.Conclusions The findings of this study suggest that p53-based gene therapy in combination with GKS may be superior to single-modality treatment of C6 glioma.

In vitro and in vivo applications of alginate/iron oxide nanocomposites for theranostic molecular imaging in a brain tumor model

RSC Advances ◽  
2015 ◽  
Vol 5 (109) ◽  
pp. 90061-90064 ◽  
Author(s):  
Chia-Hao Su ◽  
Fong-Yu Cheng
Keyword(s):  
Brain Tumor ◽  
Iron Oxide ◽  
Molecular Imaging ◽  
Tumor Model ◽  
Brain Tumor Model ◽  
Us Fda

A novel nanocomposite composed of highly safe and US-FDA-approved Fe3O4 NPs and alginate shows significant anti-brain tumor activity.

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.

Inhibitory effect of caffeic acid phenethyl ester on the growth of C6 glioma cells in vitro and in vivo

2006 ◽  
Vol 234 (2) ◽  
pp. 199-208 ◽  
Author(s):  
Hsing-Chun Kuo ◽  
Wu-Hsien Kuo ◽  
Yean-Jang Lee ◽  
Wea-Lung Lin ◽  
Fen-Pi Chou ◽  
...  
Keyword(s):  
Caffeic Acid ◽  
Glioma Cells ◽  
Caffeic Acid Phenethyl Ester ◽  
Inhibitory Effect ◽  
C6 Glioma ◽  
C6 Glioma Cells

scholarly journals Evaluation of Toxicity and Neural Uptake In Vitro and In Vivo of Superparamagnetic Iron Oxide Nanoparticles

2018 ◽  
Vol 19 (9) ◽  
pp. 2613 ◽  
Author(s):  
Muhammad Khalid ◽  
Muhammad Asad ◽  
Petra Henrich-Noack ◽  
Maxim Sokolov ◽  
Werner Hintz ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Glioma Cells ◽  
Superparamagnetic Iron Oxide ◽  
C6 Glioma ◽  
Superparamagnetic Iron Oxide Nanoparticles ◽  
C6 Glioma Cells ◽  
Oxide Nanoparticles

Superparamagnetic iron oxide nanoparticles (SPIO-NPs) have great potential to be used in different pharmaceutical applications, due to their unique and versatile physical and chemical properties. The aim of this study was to quantify in vitro cytotoxicity of dextran 70,000-coated SPIO-NPs labelled/unlabelled with rhodamine 123, in C6 glioma cells and primary hippocampal neural cells. In addition, we analyzed the in vitro and in vivo cellular uptake of labelled SPIO-NPs. The nanoparticles, with average size of 10–50 nm and polydispersity index of 0.37, were synthesized using Massart’s co-precipitation method. The concentration-dependent cytotoxicity was quantified by using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Intracellular localization of SPIO-NPs was detected by confocal laser microscopy. In vivo confocal neuroimaging (ICON) was performed on male Wistar rats after intravitreal injection followed by ex vivo retina whole mount analysis. When used for in vitro testing concentrations in the range of diagnostic and therapeutic dosages, SPIO-NPs proved to be non-cytotoxic on C6 glioma cells for up to 24 h incubation time. The hippocampal cell culture also did not show impaired viability at low doses after 24 h incubation. Our results indicate that our dextran-coated SPIO-NPs have the potential for in vivo drug delivery applications.

scholarly journals Gene Therapy with HSV1-sr39TK/GCV Exhibits a Stronger Therapeutic Efficacy Than HSV1-TK/GCV in Rat C6 Glioma Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Lei-qing Li ◽  
Fang Shen ◽  
Xiao-yan Xu ◽  
Hong Zhang ◽  
Xiao-feng Yang ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Therapeutic Efficacy ◽  
Gene Transfection ◽  
Glioma Cells ◽  
C6 Glioma ◽  
C6 Glioma Cells ◽  
Transfection Efficacy ◽  
Rat C6 Glioma

Although the combination of herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) with ganciclovir (GCV) has been shown as a promising suicide gene treatment strategy for glioma, the almost immunodepressive dose of GCV required for its adequatein vivoefficacy has hampered its further clinical application. Therefore, In order to reduce the GCV dose required, we aim to compare the therapeutic efficacy of HSV1-sr39TK, an HSV1-TK mutant with increased GCV prodrug catalytic activity, with wildtype TK in C6 glioma cells. Accordingly, rat C6 glioma cells were first transfected with pCDNA-TK and pCDNA-sr39TK, respectively, and the gene transfection efficacy was verified by immunocytochemistry and western blot analysis. Then thein vivosensitivity of these transfected C6-TK and C6-sr39TK cells to GCV was determined by 3-(4,5)-dimethylthiahiazo-(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) colorimetric assay and Hoechst-propidium iodide (PI) staining. Finally, a subcutaneously C6 xenograft tumor model was established in the nude mice to test thein vitroefficacy of TK/GCV gene therapy. Our results showed that, as compared with wildtype TK, HSV1-sr39TK/GCV demonstrated a stronger therapeutic efficacy against C6 glioma bothin vitroandin vivo, which, by reducing the required GCV dose, might warrant its future use in the treatment of glioma under clinical setting.

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