Understanding high grade glioma: Molecular mechanism, therapy and comprehensive management

Wang, Yongzhi; Jiang, Tao

doi:10.1016/j.canlet.2012.12.024

Cited by 225 publications

(183 citation statements)

References 110 publications

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“…Despite advances in surgical resection, radiotherapy, chemotherapy and other therapeutic approaches, including immune and gene therapy, the prognosis for patients with glioblastoma remains poor (3)(4)(5)(6)(7). A previous study demonstrated that the median survival time of patients with glioblastoma was 4.9 months following diagnosis (8).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-590-3p enhances the radioresistance in glioblastoma cells by targeting LRIG1

Chen

Wang

Zhu

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. microRNA (miR)-590 has been found to serve potential roles in cancer development; however, the expression and function of miR-590 in human gliomas remains to be elucidated. The present study aimed to investigate the expression of miR-590 in human glioma tissues and radioresistant human glioblastoma cells (U251R), and to determine the effect and related molecular mechanism of miR-590-3p on the radiosensitivity of U251R cells in vitro. The results from reverse transcription-quantitative polymerase chain reaction indicated that miR-590-3p was upregulated in human glioma tissues and radioresistant human glioblastoma cells, and that miR-590-3p expression was higher in high grade than in low grade gliomas. In vitro experiments revealed that the miR-590-3p inhibitor enhanced the radiosensitivity of U251R cells by suppressing cell viability, decreasing colony formation capacity and increasing cell apoptosis rate, as demonstrated by MTT, colony formation and flow cytometry analyses. A luciferase reporter assay demonstrated that leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) was a direct target of miR-590-3p. Furthermore, it was demonstrated that the effect of miR-590-3p suppression on cell viability, colony formation capacity and cell apoptosis rate was attenuated by the knockdown of LRIG1 in the U251R cells. In conclusion, the present study revealed that miR-590-3p was upregulated in human glioma tissues and radioresistant human glioblastoma cells, and miR-590-3p contributes to the radioresistance of human glioblastoma cells by directly targeting LRIG1. These findings may provide potential therapeutic strategies to prevent radioresistance in human gliomas.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-590-3p enhances the radioresistance in glioblastoma cells by targeting LRIG1

Chen

Wang

Zhu

et al. 2017

Experimental and Therapeutic Medicine

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“…Even following complex modern treatment regimens, the prognosis for patients with GBM is poor, with a median survival time of 14 months (2). The unsuccessful treatment of this aggressive disease is commonly due to late diagnosis, a lack of specific diagnostic markers, resistance to traditional treatment, and the high proliferation and metastatic potential of tumor cells (3).…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms of the effect of TGF-β1 on U87 human glioblastoma cells

Bryukhovetskiy

Шевченко

2016

Oncology Letters

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Abstract. Glioblastoma multiforme (GBM) is the most widespread and aggressive type of primary brain tumor. The prognosis following diagnosis with GBM is poor, with a median survival time of 14 months. Tumor cell invasion, metastasis and proliferation are the major causes of mortality in patients with GBM. In order to develop effective GBM treatment methods it is necessary to identify novel targets involved in these processes. Recently, there has been increasing interest in investigating the signaling pathways involved in GBM development, and the transforming growth factor-β (TGF-β) signaling pathway is understood to be significant for regulating the behavior of GBM, as well as stimulating its invasion and metastatic development. Particular interest has been given to investigating the modulation of TGF-β-induced epithelial-to-mesenchymal transition (EMT); during this process, epithelial cells transdifferentiate into mobile cells with a mesenchymal phenotype. The induction of EMT increases the invasiveness of various types of carcinoma; however, the role of TGF-β in this process remains to be elucidated, particularly in the case of GBM. The current study presents a comparative proteome mapping of the U87 human glioblastoma cell line, with and without TGF-β1 treatment. Proteome analysis identified numerous proteins involved in the molecular mechanisms of GBM oncogenesis and TGF-β1 signaling in glioblastoma. The results of the present study facilitated the identification of novel potential markers of metastasis and candidates for targeted glioblastoma therapy, which may potentially be validated and used in clinical medicine to develop improved approaches for GBM diagnosis and treatment.

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“…Beyond modeling tumor pathogenesis, the results from animal models have also identified potential targets for glioma chemotherapy (64)(65)(66)(67). The present study revealed that suppressing the nNOS enzyme improves the effects of TMZ on glioblastoma cells.…”

Section: Discussionmentioning

confidence: 66%

Function of neuronal nitric oxide synthase enzyme in temozolomide-induced damage of astrocytic tumor cells

Resende

Titze‐de‐Almeida

2018

Oncol Lett

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Abstract. Astrocytic tumors, including astrocytomas and glioblastomas, are the most common type of primary brain tumors. Treatment for glioblastomas includes radiotherapy, chemotherapy with temozolomide (TMZ) and surgical ablation. Despite certain therapeutic advances, the survival time of patients is no longer than 12-14 months. Cancer cells overexpress the neuronal isoform of nitric oxide synthase (nNOS). In the present study, it was examined whether the nNOS enzyme serves a role in the damage of astrocytoma (U251MG and U138MG) and glioblastoma (U87MG) cells caused by TMZ. First, TMZ (250 µM) triggered an increase in oxidative stress at 2, 48 and 72 h in the U87MG, U251MG and U138MG cell lines, as revealed by 2',7'-dichlorofluorescin-diacetate assay. The drug also reduced cell viability, as measured by MTT assay. U87MG cells presented a more linear decline in cell viability at time-points 2, 48 and 72 h, compared with the U251MG and U138MG cell lines. The peak of oxidative stress occurred at 48 h. To examine the role of NOS enzymes in the cell damage caused by TMZ, N(ω)-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI) were used. L-NAME increased the cell damage caused by TMZ while reducing the oxidative stress at 48 h. The preferential nNOS inhibitor 7-NI also improved the TMZ effects. It caused a 12.8% decrease in the viability of TMZ-injured cells. Indeed, 7-NI was more effective than L-NAME in restraining the increase in oxidative stress triggered by TMZ. Silencing nNOS with a synthetic small interfering (si)RNA (siRNAnNOShum_4400) increased by 20% the effects of 250 µM of TMZ on cell viability (P<0.05). Hoechst 33342 nuclear staining confirmed that nNOS knock-down enhanced TMZ injury. In conclusion, our data reveal that nNOS enzymes serve a role in the damage produced by TMZ on astrocytoma and glioblastoma cells. RNA interference with nNOS merits further studies in animal models to disclose its potential use in brain tumor anticancer therapy.

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Understanding high grade glioma: Molecular mechanism, therapy and comprehensive management

Cited by 225 publications

References 110 publications

MicroRNA-590-3p enhances the radioresistance in glioblastoma cells by targeting LRIG1

MicroRNA-590-3p enhances the radioresistance in glioblastoma cells by targeting LRIG1

Molecular mechanisms of the effect of TGF-β1 on U87 human glioblastoma cells

Function of neuronal nitric oxide synthase enzyme in temozolomide-induced damage of astrocytic tumor cells

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