Breaching barriers in glioblastoma. Part I: Molecular pathways and novel treatment approaches

Miranda, Ana; Blanco-Prieto, María J.; Sousa, João; Pais, Alberto A. C. C.

doi:10.1016/j.ijpharm.2017.07.056

Cited by 57 publications

(53 citation statements)

References 135 publications

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“…TMZ preferentially induces autophagic death in GBM cells rather than apoptosis through PI3K/AKT/mTOR signalling pathway . However, further study demonstrates that persistent inhibition of PI3K/AKT/mTOR by TMZ can only induce autophagy transiently and promote drug resistance of GBM . In the meantime, combination with autophagy inhibitors or regulators can interfere with the therapeutic effects of TMZ for GBM .…”

Section: Introductionmentioning

confidence: 92%

A risk signature with four autophagy‐related genes for predicting survival of glioblastoma multiforme

Wang

Zhao

Xiao

et al. 2020

J Cellular Molecular Medi

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Glioblastoma multiforme (GBM) is a devastating brain tumour without effective treatment. Recent studies have shown that autophagy is a promising therapeutic strategy for GBM. Therefore, it is necessary to identify novel biomarkers associated with autophagy in GBM. In this study, we downloaded autophagy-related genes from Human Autophagy Database (HADb) and Gene Set Enrichment Analysis (GSEA) website. Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis were performed to identify genes for constructing a risk signature. A nomogram was developed by integrating the risk signature with clinicopathological factors. Time-dependent receiver operating characteristic (ROC) curve and calibration plot were used to evaluate the efficiency of the prognostic model. Finally, four autophagy-related genes (DIRAS3, LGALS8, MAPK8 and STAM)were identified and were used for constructing a risk signature, which proved to be an independent risk factor for GBM patients. Furthermore, a nomogram was developed based on the risk signature and clinicopathological factors (IDH1 status, age and history of radiotherapy or chemotherapy). ROC curve and calibration plot suggested the nomogram could accurately predict 1-, 3-and 5-year survival rate of GBM patients.For function analysis, the risk signature was associated with apoptosis, necrosis, immunity, inflammation response and MAPK signalling pathway. In conclusion, the risk signature with 4 autophagy-related genes could serve as an independent prognostic factor for GBM patients. Moreover, we developed a nomogram based on the risk signature and clinical traits which was validated to perform better for predicting 1-, 3-and 5-year survival rate of GBM. K E Y W O R D Sautophagy, glioblastoma multiform, nomogram, prognosis, risk signature

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Section: Introductionmentioning

confidence: 92%

A risk signature with four autophagy‐related genes for predicting survival of glioblastoma multiforme

Wang

Zhao

Xiao

et al. 2020

J Cellular Molecular Medi

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“…Malignant glioma is an invasive intracranial tumor that grows rapidly and has extremely high recurrence (1,20). At present, postoperative chemotherapy has become a powerful strategy for the treatment of adult glioma patients (1,2,20). However, treatment has been particularly inefficient for glioma patients administered chemotherapeutic agents due to the existence of the BTB.…”

Section: Discussionmentioning

confidence: 99%

“…Glioma is characterized as a malignant brain tumor with a high recurrence rate, and surgery is utilized to remove the tumor (1,2). However, patients with glioma have a high mortality rate and an extremely poor prognosis (2).…”

Section: Introductionmentioning

confidence: 99%

“…Currently, chemotherapy is the main method for prolonging survival or reducing symptoms (3,4). It is known that the existence of the blood-tumor barrier (BTB) in tumor tissue limits the efficacy and the delivery of therapeutic agents to brain tumor tissue (1,3). Therefore, the development of therapeutic agents to pass through the BTB is increasingly needed to effectively limit the rapid and invasive growth of malignant gliomas (5,6).…”

Section: Introductionmentioning

confidence: 99%

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Caspase‑dependent apoptotic death by gadolinium chloride (GdCl3) via reactive oxygen species production and MAPK signaling in rat C6 glioma cells

Tsai¹,

Chen

Hsiao³

et al. 2018

Oncol Rep

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Gadolinium (Gd) compounds serve as magnetic resonance imaging contrast agents and exert certain anticancer activities. Yet, the molecular signaling underlying the antitumor effect of Gd chloride (GdCl 3) on glioma remains unclear. In the present study, we aimed to ascertain the apoptotic mechanisms of GdCl 3 on rat glioma C6 cells. Our results demonstrated that GdCl 3 significantly reduced cell viability and shrunk cell morphology of C6 cells in a concentration-dependent manner. GdCl 3 led to apoptotic C6 cell death as detected by TUNEL staining. An increase in cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9 occurred in GdCl 3-treated C6 cells as detected by immunoblotting analysis. The activities of caspase-3, caspase-8 and caspase-9 were increased, and the specific inhibitors of caspase-3/-8/-9 individually reversed cell viability, which caused apoptotic death in C6 cells prior to GdCl 3 exposure. GdCl 3 also caused an elevation in the cytoplasmic Ca 2+ level and reactive oxygen species (ROS) production, as well as the loss of mitochondrial membrane potential (ΔΨm) as shown by flow cytometric analysis in C6 cells. The results from the immunoblotting analysis demonstrated that there were upregulated protein levels of cytochrome c and Bax but a downregulated protein level of Bcl-2 in C6 cells after GdCl 3 treatment. Additionally, GdCl 3 decreased the protein levels of phosphorylated-extracellular signal-regulated kinases, phosphorylated-c-Jun N-terminal kinase and phosphorylated-p38 mitogen-activated protein kinases in C6 cells. In conclusion, ROS production and MAPKs signaling pathways contribute to GdCl 3-induced caspase cascade-mediated apoptosis in C6 cells. Our findings provide a better understanding of the molecular mechanisms underlying the role of GdCl 3 in rat glioma C6 cells.

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“…Despite multidisciplinary treatment approaches, including surgical resection and radiotherapy, GBM has a low prognosis with an average survival period of 15 -18 months (124)(125)(126). A major challenge in the treatment of GBM is delivering the therapeutic drug across the blood-brain barrier (BBB), a network of specialized brain endothelial cells with intercapillary distances of ~40µm that tightly regulate ionic composition, prevent macromolecules and unwanted cells from entering the brain to protect the central nervous system (CNS) from neurotoxins (127)(128)(129)(130)(131). The use of targeted drug delivery with relatively small magnetic particles (<40-nm) has been suggested as an efficient way to cross BBB, target cancerous cells, and permit an ondemand release of anti-tumor drugs.…”

Section: Introductionmentioning

confidence: 99%

Technobiology Paradigm in Nanomedicine: Treating Cancer with MagnetoElectric Nanoparticles

Stimphil¹

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Breaching barriers in glioblastoma. Part I: Molecular pathways and novel treatment approaches

Cited by 57 publications

References 135 publications

A risk signature with four autophagy‐related genes for predicting survival of glioblastoma multiforme

A risk signature with four autophagy‐related genes for predicting survival of glioblastoma multiforme

Caspase‑dependent apoptotic death by gadolinium chloride (GdCl3) via reactive oxygen species production and MAPK signaling in rat C6 glioma cells

Technobiology Paradigm in Nanomedicine: Treating Cancer with MagnetoElectric Nanoparticles

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