Malignant gliomas: old and new systemic treatment approaches

Mesti, Tanja; Ocvirk, Janja

doi:10.1515/raon-2015-0003

Cited by 29 publications

(16 citation statements)

References 76 publications

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“…The current standard therapy for GBM patients includes maximal debulking surgery, radiation and adjuvant chemotherapy. Temozolomide, a current chemotherapeutic agent of choice for GBM patients, has yielded only very modest improvements in disease outcomes (4).…”

Section: Introductionmentioning

confidence: 99%

High ATP2A2 expression correlates with better prognosis of diffuse astrocytic tumor patients

Zhong

et al. 2017

Oncology Reports

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Novel molecular markers are required for defining subsets of diffuse astrocytic tumor patients with differing prognoses. Here, we examined ATP2A2 expression in 109 human diffuse astrocytic tumor samples (39 grade II diffuse astrocytoma (DA), 19 grade III anaplastic astrocytoma (AA), 51 grade IV glioblastoma) and its correlation with patient clinicopathologic characteristics. ATP2A2 expression significantly correlated with tumor grade and survival (P<0.05). High ATP2A2 expression was detected in 35.3% (18/51) of glioblastoma patients, compared to 61.5% (24/39) in grade II, and 52.6% (10/19) in grade III astrocytoma patients (P=0.043). The median survival was 45±5.3 (95% CI, 34.7-55.3) months in patients with high ATP2A2 expression and 16±5.0 (95% CI, 6.3-25.7) months in patients with low ATP2A2 expression (P<0.0001). Additionally, high grade astrocytoma patients with high ATP2A2 expression showed longer survival (median, 31.0±4.9 months, 95% CI, 21.4-40.7) than those with low ATP2A2 expression (median: 13.0±1.6 months, 95% CI, 9.9-16.1; P=0.027). Furthermore, both ATP2A2 overexpression and IDH1 mutation were detected in secondary glioblastoma, AA developed from DA and oligodendrogiomas with IDH1 mutation. The MTT assays showed that lentiviral ATP2A2 overexpression significantly suppressed the clonogenic growth of glioblastoma U251MG cells (P<0.05). Xenografts stably overexpressing ATP2A2 were markedly smaller in size 4 weeks post inoculation (P<0.05). Our findings identified high ATP2A2 expression in a subset of astrocytoma patients that was associated with better prognosis and ATP2A2 suppressed astrocytoma growth.

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Section: Introductionmentioning

confidence: 99%

High ATP2A2 expression correlates with better prognosis of diffuse astrocytic tumor patients

Zhong

et al. 2017

Oncology Reports

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“…Currently glioma treatments have shown low effectiveness for the outcome of patients with glioma, which have emphasized the need for new molecularly targeted therapies ( 11 , 13 ). Gliomas are aggressive and their incidence rate in patients is increasing, resulting in a relative high mortality rate ( 13 , 14 ).…”

Section: Discussionmentioning

confidence: 99%

Tunicamycin inhibits progression of glioma cells through downregulation of the MEG‑3‑regulated wnt/β‑catenin signaling pathway

Xue

Qin

2018

Oncol Lett

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Glioma is derived from the oncogenic transformation of brain and spinal cord glial cells, and is one of the most common primary brain tumors. Tunicamycin (TUN) can significantly inhibit glioma growth and aggressiveness by promoting apoptosis in glioma cells. The purpose of the present study was to investigate the effects of TUN on growth of glioma cells and examine the TUN-mediated signaling pathway. The inhibitory effects of TUN on apoptosis, growth, aggressiveness and cell cycle arrest of glioma tumor cells were determined by western blotting, reverse transcription-quantitative polymerase chain reaction, apoptotic assays and immunofluorescence. The results demonstrated that treatment with TUN suppressed growth, migration and invasion of glioma carcinoma cells. In addition, TUN treatment induced apoptosis of glioma cells through downregulation of Bcl-2 and P53 expression levels. Findings also indicated that TUN suppressed proliferation and arrested the glioma cells in the S phase of the cell cycle. Further analysis of the mechanisms of TUN demonstrated that TUN treatment upregulated the expression levels of maternally expressed gene (MEG)-3, wnt and β-catenin in glioma cells. Furthermore, knockdown of MEG-3 expression reversed the TUN-decreased wnt/β-catenin signaling pathway, which subsequently also reversed the TUN-inhibited growth and aggressiveness of glioma cells. In conclusion, the findings in the present study indicated that TUN treatment inhibited growth and aggressiveness through MEG-3-mediated wnt/β-catenin signaling, suggesting that TUN may be an efficient anticancer agent for the treatment of glioma.

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“…Currently, the antiglioma therapies, including chemoradiotherapy and biotherapy are efficient for patients with cancer (17,18). Incidence rates of gliomas are increasing (19,20). Evidence suggests that tunicamycin may inhibit tumor growth and promote apoptosis mediated by tumor necrosis factor-related apoptosis-inducing ligand (10,21).…”

Section: Discussionmentioning

confidence: 99%

MEG‑3‑mediated Wnt/β‑catenin signaling pathway controls the inhibition of tunicamycin‑mediated viability in glioblastoma

et al. 2018

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Glioblastoma is the most common primary brain carcinoma and leads to a poor survival rate of patients worldwide. Results of previous studies have suggested that tunicamycin may inhibit aggressiveness by promoting apoptosis of glioblastoma cells. In the present study, the effects of tunicamycin and its potential molecular mechanisms underlying the viability and aggressiveness of glioblastoma cells were investigated. Western blot analysis, the reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, apoptosis assays and immunofluorescence were employed to examine the effects of tunicamycin on apoptosis, viability, aggressiveness and cell cycle arrest of glioblastoma cells by downregulation of the expression levels of fibronectin and epithelial cadherin. In vitro experiments demonstrated that tunicamycin significantly inhibited the viability, migration and invasion of glioblastoma cells. Results demonstrated that tunicamycin administration promoted apoptosis of glioblastoma cells through the upregulation of poly(ADP-ribose) polymerase and caspase-9. Cell cycle assays revealed that tunicamycin suppressed the proliferation of, and induced cell cycle arrest at S phase in, glioblastoma cells. Additionally, tunicamycin increased the expression of maternally expressed gene-3 (MEG-3) and wingless/integrated (Wnt)/β-catenin in glioblastoma cells. Results also indicated that tunicamycin administration promoted the Wnt/β-catenin signaling pathway in glioblastoma cells. Knockdown of MEG-3 inhibited tunicamycin-mediated downregulation of the Wnt/β-catenin signaling pathway, which was inhibited further by tunicamycin-mediated inhibition of viability and aggressiveness in glioblastoma. In vivo assays demonstrated that tunicamycin treatment significantly inhibited tumor viability and promoted apoptosis, which further led to an increased survival rate of tumor-bearing mice compared with that of the control group. In conclusion, these results indicate that tunicamycin may inhibit the viability and aggressiveness by regulating MEG-3-mediated Wnt/β-catenin signaling, suggesting that tunicamycin may be a potential anticancer agent for glioblastoma therapy.

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Malignant gliomas: old and new systemic treatment approaches

Cited by 29 publications

References 76 publications

High ATP2A2 expression correlates with better prognosis of diffuse astrocytic tumor patients

High ATP2A2 expression correlates with better prognosis of diffuse astrocytic tumor patients

Tunicamycin inhibits progression of glioma cells through downregulation of the MEG‑3‑regulated wnt/β‑catenin signaling pathway

MEG‑3‑mediated Wnt/β‑catenin signaling pathway controls the inhibition of tunicamycin‑mediated viability in glioblastoma

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