Tumor stem cells from glioblastoma multiforme

Никифорова, З. Н.; Кудрявцев, И. А.; Арноцкая, Н. Е.; Брюховецкий, И. С.; Шевченко, В. Е.

doi:10.17650/2313-805x.2016.3.2.26-33

Cited by 4 publications

(2 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Over the past decade, more efforts have been taken to block GBM. Unfortunately, GBM treatment is still limited and insufficiently studied 4 ; moreover, difficult overall prognosis, undesirable surgical resection, and radio- or chemoresistance make this disease more troublesome 5 . Thus, a better understanding of GBM and its underlying pathogenic mechanisms will provide us new possibilities for more specific and satisfactory therapies.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Proliferation by Knockdown of Transmembrane (TMEM) 168 in Glioblastoma Cells via Suppression of Wnt/β-Catenin Pathway

Ding

et al. 2019

oncol res

View full text Add to dashboard Cite

Human glioblastoma multiforme (GBM) accounts for the majority of human brain gliomas. Several TMEM proteins, such as TMEM 45A, TMEM 97, and TMEM 140, are implicated in human brain gliomas. However, the roles of TMEM168 in human GBM remain poorly understood. Herein we found that mRNA levels of TMEM168 were overexpressed in GBM patients ( n = 85) when compared with healthy people ( n = 10), which was also supported by data from The Cancer Genome Atlas (TCGA). Kaplan–Meier analysis of Gene Expression Omnibus dataset GSE16011 suggested that enhanced TMEM168 expression was associated with shorter survival time. To investigate whether and how TMEM168 functioned in the tumorigenesis of human GBM cells, two human GBM cell lines (U87 and U373) were used for study. Lithium chloride (LiCl), an activator for Wnt/β-catenin pathway, was used for the treatment. Our data suggested that siRNA-TMEM168 (siTMEM168) prevented viability of U87 and U373 cells, induced cell cycle arrest (G 0 /G 1 phase) and promoted apoptosis, and the mechanisms involved in blocking Wnt/β-catenin pathway, as evidenced by reducing expression of β-catenin, C-myc, cyclin D1, and survivin. Furthermore, the inhibited effect of siTMEM168 on human GBM cell growth was significantly alleviated with additional LiCl treatment, substantiating the involvement of the Wnt/β-catenin pathway in this process. In summary, our data demonstrated that TMEM168 may represent a therapeutic target for the treatment of human GBM.

show abstract

Section: Introductionmentioning

confidence: 99%

Inhibition of Proliferation by Knockdown of Transmembrane (TMEM) 168 in Glioblastoma Cells via Suppression of Wnt/β-Catenin Pathway

Ding

et al. 2019

oncol res

View full text Add to dashboard Cite

show abstract

“…Glioblastoma multiforme (GBM) accounts for about 80% of all glioblastomas [1], and is the most invasive and deadly form of human malignant brain cancer [2], with an average survival of only 14 months after diagnosis [3]. GBM treatment is limited and insufficiently studied [4] due to poor prognosis, undesirable surgical resection, and radio- or chemo-resistance [5]. Thus, a better understanding of GBM and its underlying pathogenic mechanisms is necessary to manage this disease.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Tripartite Motif-Containing 48 (TRIM48) Inhibits Growth of Human Glioblastoma Cells by Suppressing Extracellular Signal Regulated Kinase 1/2 (ERK1/2) Pathway

et al. 2019

View full text Add to dashboard Cite

BackgroundHerein, we found that tripartite motif-containing 48 (TRIM48) was reduced in human glioblastoma (GBM) cell lines. We investigated whether and how TRIM48 functions in human GBM in vitro.Material/MethodsHuman GBM cells (U87 MG and U138 MG) were infected with lentivirus to overexpress TRIM48, and 1 human GBM cell line (T98G) was infected with siRNAs to knock down TRIM48 expression. Techniques used included cell proliferation assay, measured by CCK-8 and BrdU-ELISA method, and cell cycle assay, determined using flow cytometry. Curcumin, a specific activator of extracellular signal regulated kinases (ERK1/2), or PD98059, a specific inhibitor of ERK1/2, was used to activate or block the ERK1/2 pathway, respectively. Expression of phosphorylated (p)-ERK1/2, and its downstream targets (Cyclin D1) were measured to assess the mechanism.ResultsOur data suggest that overexpression of TRIM48 reduces the viability of U87 MG and U138 MG and leads to cell cycle arrest (in G0-G1 phase), which is associated with blockade of the ERK1/2 pathway and reduction of Cyclin D1. In contrast, knockdown of TRIM48 resulted in the opposite effects. Interestingly, the inhibitory effect of TRIM48 overexpression on human GBM cell growth and the inactivation of ERK1/2 were significantly alleviated with additional curcumin treatment, while it the promoted the effect of siTRIM48 on human GBM cell growth, and the activation of ERK1/2 was significantly alleviated with additional PD98059 treatment.ConclusionsTRIM48 suppressed the growth of human GBM cell via the prevention of ERK1/2 activation.

show abstract

Evaluation of a strategy for tumor-initiating stem cell eradication in primary human glioblastoma cultures as a model

et al. 2018

View full text Add to dashboard Cite

Primary cultures of human glioblastoma were obtained from the surgical material of patients K. (female, 61 years, Ds: relapse of glioblastoma) and Zh. (female, 60 years, Ds: relapse of glioblastoma). The effectiveness of a new therapeutic approach aimed at destroying the cancer cell community was evaluated on the primary cell lines of human glioblastoma culture by employing a new strategy of tumor-initiating stem cell synchronization and a domestic strategy of their eradication "3+1". The key elements of the strategy were the following indicator results: (1) evaluation of the presence of tumor-initiating stem cells in a population of cells from analyzed cultures by their ability to internalize double-stranded labeled DNA (TAMRA+ cells); (2) determination of the reference time points of the repair cycle of DNA interstrand cross-links induced by cross-linking cytostatic mitomycin C; (3) evaluation of cell cycle synchronization; (4) determination of the time (day after therapy initiation) when TAMRA+ cells were synchronously present in phase G1/S of the cell cycle, sensitive to the therapy; and (5) establishment of the TAMRA+ (tumor-initiating stem cells) eradication schedule. The cultures were treated with cross-linking cytostatic mitomycin C and a compositional DNA preparation. After the treatments, cell division slows down, and the cultures degrade. The K cell line completely degraded within 30 days of observation. The cell number of the Zh culture fell to nearly one-third of the starting value by day 15 of observation. On day 15, this indicator constituted 1/7.45 for mitomycin C and 1/10.28 for mitomycin C + DNA with reference to the control. The main target of the mitomycin C + DNA regimen was TAMRA+ tumor-initiating stem cells of the glioblastoma cell populations. The action of mitomycin C alone or in the combination with DNA demonstrated effective elimination of TAMRA+ tumor-initiating stem cells and the whole primary cultures of human glioblastomas.

show abstract

Tumor stem cells from glioblastoma multiforme

Abstract: (miR-21, miR-128, miR-326, miR-34a)

Cited by 4 publications

References 61 publications

Inhibition of Proliferation by Knockdown of Transmembrane (TMEM) 168 in Glioblastoma Cells via Suppression of Wnt/β-Catenin Pathway

Inhibition of Proliferation by Knockdown of Transmembrane (TMEM) 168 in Glioblastoma Cells via Suppression of Wnt/β-Catenin Pathway

Overexpression of Tripartite Motif-Containing 48 (TRIM48) Inhibits Growth of Human Glioblastoma Cells by Suppressing Extracellular Signal Regulated Kinase 1/2 (ERK1/2) Pathway

Evaluation of a strategy for tumor-initiating stem cell eradication in primary human glioblastoma cultures as a model

Contact Info

Product

Resources

About