Glioma: experimental models and reality

Lenting, Krissie; Verhaak, Roel G.W.; Laan, Mark ter; Wesseling, Pieter; Leenders, William P. J.

doi:10.1007/s00401-017-1671-4

Cited by 237 publications

(213 citation statements)

References 165 publications

Supporting

Mentioning

205

Contrasting

Unclassified

Order By: Relevance

“…For this reason models that are closer to the in vivo situation, for instance, glioma PDX models have an advantage. 34 A relative large panel of inhibitors that target enzymes or transporters of the glutamate metabolism exist. 19 The inhibitors open possibilities to target these enzymes in metabolic flux experiments in IDH1-mutated glioma PDX models to validate the findings in this study.…”

Section: F I G U R E 5 Abundance Plots Of the Aerobic Glycolysis And mentioning

confidence: 99%

Metabolic changes related to the IDH1 mutation in gliomas preserve TCA‐cycle activity: An investigation at the protein level

Dekker

Jurriëns

et al. 2020

FASEB j.

View full text Add to dashboard Cite

The discovery of the IDH1 R132H (IDH1 mut) mutation in low‐grade glioma and the associated change in function of the IDH1 enzyme has increased the interest in glioma metabolism. In an earlier study, we found that changes in expression of genes involved in the aerobic glycolysis and the TCA cycle are associated with IDH1 mut. Here, we apply proteomics to FFPE samples of diffuse gliomas with or without IDH1 mutations, to map changes in protein levels associated with this mutation. We observed significant changes in the enzyme abundance associated with aerobic glycolysis, glutamate metabolism, and the TCA cycle in IDH1 mut gliomas. Specifically, the enzymes involved in the metabolism of glutamate, lactate, and enzymes involved in the conversion of α‐ketoglutarate were increased in IDH1 mut gliomas. In addition, the bicarbonate transporter (SLC4A4) was increased in IDH1 mut gliomas, supporting the idea that a mechanism preventing intracellular acidification is active. We also found that enzymes that convert proline, valine, leucine, and isoleucine into glutamate were increased in IDH1 mut glioma. We conclude that in IDH1 mut glioma metabolism is rewired (increased input of lactate and glutamate) to preserve TCA‐cycle activity in IDH1 mut gliomas.

show abstract

Section: F I G U R E 5 Abundance Plots Of the Aerobic Glycolysis And mentioning

confidence: 99%

Metabolic changes related to the IDH1 mutation in gliomas preserve TCA‐cycle activity: An investigation at the protein level

Dekker

Jurriëns

et al. 2020

FASEB j.

View full text Add to dashboard Cite

show abstract

“…The molecular biology of GBM is highly heterogeneous. Despite advances in the technical proficiencies of surgical and radiation oncology, patients with GBM have a poor prognosis, with a median survival of less than one year from the time of diagnosis and a five-year mortality of over 95% [5][6][7]. To date, the pathogenesis of GBM is still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

EYA4 Promotes Cell Proliferation Through Downregulation of p27Kip1 in Glioma

Qiu

Xia³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Accumulating evidence suggests that Eyes Absent Homologue 4 (EYA4) plays an important role in tumorigenesis and progression of various cancers. However, the role of EYA4 in glioma development is still unclear. Methods: The expression of EYA4 was examined in glioma tissues by immunohistochemistry. Cell viability and apoptosis were analyzed by CCK-8, BrdU assay, and flow cytometry. Results: We found that EYA4 was upregulated in glioma, and its expression was positively correlated with advanced tumor stage. Moreover, higher expression of EYA4 predicted a worse overall survival in patients with glioma. Forced overexpression of EYA4 enhanced glioma cell proliferation, and EYA4 suppressed the expression of p27Kip1 directly in these cells. Furthermore, Six1 was required for EYA4 to suppress the expression of p27Kip1 in glioma. Conclusion: Together, we demonstrate that EYA4 promotes cell proliferation by directly suppressing the expression of p27Kip1 in glioma.

show abstract

“…Understanding the biology of astrocytic cells is a challenging effort for studies that use animal models of brain tumors (61)(62)(63). Beyond modeling tumor pathogenesis, the results from animal models have also identified potential targets for glioma chemotherapy (64)(65)(66)(67).…”

Section: Discussionmentioning

confidence: 99%

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

Resende

Titze‐de‐Almeida

2018

Oncol Lett

View full text Add to dashboard Cite

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.

show abstract

Glioma: experimental models and reality

Cited by 237 publications

References 165 publications

Metabolic changes related to the IDH1 mutation in gliomas preserve TCA‐cycle activity: An investigation at the protein level

Metabolic changes related to the IDH1 mutation in gliomas preserve TCA‐cycle activity: An investigation at the protein level

EYA4 Promotes Cell Proliferation Through Downregulation of p27Kip1 in Glioma

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

Contact Info

Product

Resources

About