scholarly journals A Double-Switch Cell Fusion-Inducible Transgene Expression System for Neural Stem Cell-Based Antiglioma Gene Therapy

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Yumei Luo ◽  
Detu Zhu ◽  
Dang Hoang Lam ◽  
Juan Huang ◽  
Yi Tang ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Cell Fusion ◽  
Transgene Expression ◽  
Glioma Cell ◽  
Expression System ◽  
Glioma Cells ◽  
Luciferase Reporter ◽  
Double Switch

Recent progress in neural stem cell- (NSC-) based tumor-targeted gene therapy showed that NSC vectors expressing an artificially engineered viral fusogenic protein, VSV-G H162R, could cause tumor cell death specifically under acidic tumor microenvironment by syncytia formation; however, the killing efficiency still had much room to improve. In the view that coexpression of another antitumoral gene with VSV-G can augment the bystander effect, a synthetic regulatory system that triggers transgene expression in a cell fusion-inducible manner has been proposed. Here we have developed a double-switch cell fusion-inducible transgene expression system (DoFIT) to drive transgene expression upon VSV-G-mediated NSC-glioma cell fusion. In this binary system, transgene expression is coregulated by a glioma-specific promoter and targeting sequences of a microRNA (miR) that is highly expressed in NSCs but lowly expressed in glioma cells. Thus, transgene expression is “switched off” by the miR in NSC vectors, but after cell fusion with glioma cells, the miR is diluted and loses its suppressive effect. Meanwhile, in the syncytia, transgene expression is “switched on” by the glioma-specific promoter. Ourin vitroandin vivoexperimental data show that DoFIT successfully abolishes luciferase reporter gene expression in NSC vectors but activates it specifically after VSV-G-mediated NSC-glioma cell fusion.

Inhibition of Glioma Cell Proliferation by Neural Stem Cell Factor

2005 ◽  
Vol 74 (3) ◽  
pp. 233-239 ◽  
Author(s):  
Tsuyoshi Suzuki ◽  
Shuichi Izumoto ◽  
Kouichi Wada ◽  
Yasunori Fujimoto ◽  
Motohiko Maruno ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Stem Cell Factor ◽  
Glioma Cell ◽  
Glioma Cell Proliferation

scholarly journals miR-6869-5p Inhibits Glioma Cell Proliferation and Invasion via Targeting PGK1

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Fakai Wang ◽  
Huanjun Zhang ◽  
Bing Liu ◽  
Wei Liu ◽  
Zengchao Zhang
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Negative Association ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Glioma Cell Proliferation ◽  
Precise Role ◽  
Proliferation And Invasion

Accumulating studies have suggested the dysregulated microRNAs (miRNAs) play important roles in brain tumors, including glioma. miR-6869-5p has been documented to be aberrantly expressed in diverse cancers. However, the precise role of miR-6869-5p in glioma remains poorly understood. This study is aimed at evaluating its modifying effects on glioma. Significantly decreased expression of miR-6869-5p was found in glioma tissues and cells. Negative association was documented between miR-6869-5p and PGK1 in glioma cells, and PGK1 was demonstrated to be a targeted gene of this miRNA by luciferase reporter assay. miR-6869-5p regulated glioma cell proliferation and invasion via targeting PGK1. In addition, the survival analysis had suggested that low miR-6869-5p expression predicted poor prognosis of glioma patients. This study has suggested that miR-6869-5p is a useful tumor suppressor and prognostic marker in glioma.

scholarly journals Induced transgene expression for the treatment of solid tumors by hematopoietic stem cell-based gene therapy

2012 ◽  
Vol 19 (5) ◽  
pp. 352-357 ◽  
Author(s):  
F Noyan ◽  
I Avedillo Díez ◽  
M Hapke ◽  
C Klein ◽  
R A Dewey
Keyword(s):  
Gene Therapy ◽  
Stem Cell ◽  
Solid Tumors ◽  
Hematopoietic Stem Cell ◽  
Transgene Expression ◽  
Hematopoietic Stem

scholarly journals Neural Stem Cell–Based Anticancer Gene Therapy: A First-in-Human Study in Recurrent High-Grade Glioma Patients

2016 ◽  
Vol 23 (12) ◽  
pp. 2951-2960 ◽  
Author(s):  
Jana Portnow ◽  
Timothy W. Synold ◽  
Behnam Badie ◽  
Revathiswari Tirughana ◽  
Simon F. Lacey ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Human Study ◽  
High Grade Glioma ◽  
High Grade

Interferon-Inducible Mx Promoter-Driven, Long-Term Transgene Expression System of Interferon-β for Cancer Gene Therapy

2016 ◽  
Vol 27 (11) ◽  
pp. 936-945 ◽  
Author(s):  
Atsushi Hamana ◽  
Yuki Takahashi ◽  
Makiya Nishikawa ◽  
Yoshinobu Takakura
Keyword(s):  
Gene Therapy ◽  
Transgene Expression ◽  
Expression System ◽  
Cancer Gene Therapy ◽  
Cancer Gene ◽  
Interferon Β

scholarly journals Tumor-tumor Cell Fusion Hybrids Obtained by the Modified PHA-DMSO-PEG Method Promote Temozolomide Resistance in Glioma

2021 ◽  
Author(s):  
Ruifang Mi ◽  
Jiayu Ji ◽  
Mingxin Li ◽  
Mengmeng Zhang ◽  
Junwen Zhang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Tumor Cell ◽  
Cell Fusion ◽  
Dna Content ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Giant Cells ◽  
Fusion Method ◽  
Fusion Efficiency

Abstract Background: Cell fusion and the subsequent aneuploidy are commonly observed in different kinds of tumor. In glioma, cell fusion and the number of the polyploid giant cells were found to be augmented with the tumor grades (WHO Ⅰ-Ⅳ) and closely related to poor prognosis. Phytohemagglutinin (PHA) holds an ability to induce cell-cell membrane contact and accelerates the cell fusion process mediated by the fusogenic agent polyethylene glycol (PEG). Dimethyl sulfoxide (DMSO) is well known as a cryoprotective agent involving in cell cryopreservation. In this study, we aim to obtain the glioma fusion hybrids by the modified fusion method in vitro, and then investigate the pathological consequences and the related molecular mechanism with the cell hybrids.Methods: Glioma cells were labelled by lentiviruses infection. The PEG fusion efficiency was respectively improved by the addition of PHA and DMSO, and quantified by flow cytometry. Then, fusion hybrids were obtained by puromycin screening and fluorescence-activated cell sorting (FACS). Furthermore, DNA content was analyzed through flow cytometry. Cell proliferation rate and cell viability under temozolomide (TMZ) was detected by CCK-8 assay. Lastly, the related gene expression was measured through qRT-PCR and Western blotting. Results: Glioma cell-cell contact was achieved by adding certain concentration of PHA in vitro. Tumor-tumor cell fusion efficiency was improved by PHA and DMSO. Glioma fusion hybrids were successfully obtained after puromycin screening and FACS. Cell size, DNA content and chromosome numbers of the fusion hybrids were almost twice that of the parental glioma cells. Moreover, glioma fusion hybrids showed an enhanced TMZ resistance potential compared to the parental cells, and also the MGMT expression was up-regulated in the hybrids.Conclusions: We successfully obtained the glioma tumor-tumor cell fusion hybrids through the modified PHA-DMSO-PEG fusion method. Cell fusion may contribute to TMZ resistance in glioma, thus inhibition of cell fusion could be a promising orientation to improve TMZ resistance. Moreover, combining TMZ and MGMT inhibitor could be a beneficial approach in patients with glioma polyploid giant cells.

miR-16 Inhibits Extracellular Signal-Regulated Kinases (ERK) Mitogen-Activated Protein Kinases (MAPK) Signaling to Affect Epithelial-Mesenchymal Transition (EMT) and Invasion of Glioma Cells

2022 ◽  
Vol 12 (4) ◽  
pp. 848-853
Author(s):  
Peng Sun ◽  
Duojiao Fan ◽  
Jing Cao ◽  
Haiyan Zhou ◽  
Fan Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Epithelial Mesenchymal Transition ◽  
Glioma Cells ◽  
Mapk Signaling ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
U251 Cells ◽  
E Cadherin

Abnormal MEK1 expression is associated with tumor cell EMT, invasion and metastasis. Decreased miR-16 level is associated with glioma. Bioinformatics analysis showed a relationship between miR-16 and MEK1. This study assessed whether miR-16 regulates MEK1 expression and affects glioma cell EMT and invasion. The tumor tissues and adjacent glioma tissues were collected to measure miR-16 and MEK1 mRNA. The dual luciferase assay validated the relation of miR-16 with MEK1. U251 cells were cultured and assigned into NC group and mimic group, followed by analysis of cell biological behaviors, and MEK1, p-ERK1/2, E-cadherin, N-Cadherin expression. Compared with adjacent tissues, miR-16 expression was significantly decreased and MEK1 was elevated in glioma tissues. Compared with HEB, miR-16 in glioma U251 and SHG44 cells was decreased and MEK1 was increased. Dual luciferase reporter gene experiments confirmed the relation of miR-16 with MEK1. Transfection of miR-16 mimic significantly down-regulated MEK1, p-ERK1/2 and N-cadherin in U251 cells, upregulated E-cadherin, inhibited cell proliferation, promoted apoptosis, and attenuated EMT and invasion of glioma cells. In conclusion, decreased miR-16 expression and increased MEK1 expression is related to glioma pathogenesis. Overexpression of miR-16 can inhibit MEK1 expression, ERK/MAPK signaling, glioma cell proliferation, promote apoptosis, and attenuate EMT and invasion.

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