New clues in the malignant progression of glioblastoma: can thioredoxin system play a role?

Erdi, Fatih; Kaya, Bülent; Esen, Hasan; Karataş, Yaşar; Fındık, Sıddıka; Keskin, Fatıh; Feyzioğlu, Bahadır; Kalkan, Erdal

doi:10.5137/1019-5149.jtn.18991-16.2

Cited by 8 publications

(8 citation statements)

References 15 publications

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“…In a study of 27 GBM cases, Kemerdere et al [21] reported that serum and tissue levels of TrxR were increased in GBM patients, but this study did not assess associations with patient survival. A study investigating 40 GBM patients showed significantly higher TrxR expression in primary GBMs with TrxR expression highly correlating with the Ki-67 index, but the study also did not assess for associations with patient survival [29]. A further study assessed TrxR in 20 GBM patients, showing higher TrxR expression in GBMs containing intratumoural haemorrhage, suggesting a role for TrxR in the promotion of tumour angiogenesis and growth, but again, associations with patient survival were not presented [30].…”

Section: Discussionmentioning

confidence: 98%

Thioredoxin System Protein Expression Is Associated with Poor Clinical Outcome in Adult and Paediatric Gliomas and Medulloblastomas

et al. 2020

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The thioredoxin (Trx) system is an important enzyme family that regulates cellular redox homeostasis. Protein expression of Trx system family members has been assessed in various cancers and linked to various clinicopathological variables, disease progression, treatment response and survival outcomes but information is lacking in brain tumours. Expression of the system was therefore examined, by immunohistochemistry in different brain tumour types, adult and paediatric cases, to determine if expression was of importance to clinical outcome. Trx system proteins were expressed, to variable levels, across all brain tumour types with significant variations in expression between different tumour types/grades/regions. High Trx reductase (TrxR) expression was linked to worse prognosis across all cohorts. High cytoplasmic TrxR expression was significantly associated with adverse overall survival (OS) in adult glioblastoma (P = 0.027) and paediatric low-grade glioma (LGG) patients (P = 0.012). High expression of nuclear TrxR, cytoplasmic and nuclear Trx and Trx-interacting protein (TxNIP) was associated with improved OS in paediatric LGGs (P = 0.031, P < 0.001, P = 0.044 and P = 0.018, respectively). For patients with high-grade gliomas, both high cytoplasmic TrxR and Trx expression were associated with poor OS (P = 0.002 and P = 0.007, respectively). In medulloblastoma, high expression of cytoplasmic TrxR and Trx and nuclear Trx was associated with worse prognosis (P = 0.013, P = 0.033 and P = 0.007, respectively); with cytoplasmic TrxR and nuclear Trx remaining so in multivariate analysis (P = 0.009 and P = 0.013, respectively). The consistent finding that high levels of cytoplasmic TrxR are associated with a worse prognosis across all cohorts suggests that TrxR is an important therapeutic target in brain cancers.

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Section: Discussionmentioning

confidence: 98%

Thioredoxin System Protein Expression Is Associated with Poor Clinical Outcome in Adult and Paediatric Gliomas and Medulloblastomas

et al. 2020

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“…The Transcriptor First Strand c-DNA Synthesis Kit (Roche Applied Science) was used to generate c-DNA from RNA, according to the manufacturer's instructions; 10 μL total RNA was used for amplification. [9] Amplification reactions were set up in a reaction volume of 20 μL using the LightCycler 480 PCR Master Mix (Roche Applied Science, cat. 04707494001).…”

Section: Rna Isolation and Qrt-pcrmentioning

confidence: 99%

“…Amplification was performed for 40 cycles at 95°C for 10 seconds, followed by 60°C for 30 seconds, and 72°C for 1 second. [9] Quantification was achieved using the comparative CT method, normalizing against the 18S ribosomal RNA (18S) gene. The expression levels in tumor tissues relative to the non-tumor controls were assessed using the 2 −ΔΔCt method.…”

Section: Rna Isolation and Qrt-pcrmentioning

confidence: 99%

Increased expression of ubiquitin C-terminal hydrolase L1 in astrocytomas of ascending grades

et al. 2023

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Background: The ubiquitin-proteasome pathway controls the monitoring and degradation of important proteins and is involved in several cellular processes, such as development, differentiation, and transcriptional regulation. Recent evidence has shown that ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), a member of the deubiquitinating enzyme family that removes ubiquitin from protein substrates, is overexpressed in many types of cancer. Aim: This study thus examined the expression of UCH-L1 in human astrocytoma tissues. Material and methods: Formalin-fixed, paraffin-embedded astrocytoma samples were obtained from 40 patients, after which histopathological examination, typing, and grading were performed. The study group included 10 histologically normal brain tissues, which served as the control group, and 10 WHO grade II, 10 WHO grade III, and 10 WHO grade IV (glioblastoma) samples. Normal brain tissue samples were obtained from the histologically normal, non-tumoral portion of the pathology specimens. UCH-L1 expression was evaluated using quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. Results: Astrocytoma tissues exhibited higher UCH-L1 expression compared to the control group. UCH-L1 overexpression increased significantly together with the increase in astrocytoma grades (from II to IV). Conclusion: UCH-L1 could be a good diagnostic and therapeutic marker for determining astrocytoma development and progression.

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“…Nuclear factor (erythroid-derived 2)-like 2 (NRF2) regulates redox dynamics and favors an M2 phenotype with cytoprotective effects ( 167 , 168 ). Additionally, glioma cells and stromal cells maintain a pool of antioxidant peptides, such as glutathione and thioredoxin, protecting them against radiation- induced redox ( 169 , 170 ). Differential ability of glioma cells to modulate redox reactions may be a mechanism by which certain cancer cells are more radioresistant than others.…”

Section: Effects Of Radiation Therapy On the Gbm Microenvironmentmentioning

confidence: 99%

Radiation-Induced Alterations in the Recurrent Glioblastoma Microenvironment: Therapeutic Implications

Gupta

Burns

2018

Front. Oncol.

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Glioblastoma (GBM) is uniformly fatal with a median survival of just over 1 year, despite best available treatment including radiotherapy (RT). Impacts of prior brain RT on recurrent tumors are poorly understood, though increasing evidence suggests RT-induced changes in the brain microenvironment contribute to recurrent GBM aggressiveness. The tumor microenvironment impacts malignant cells directly and indirectly through stromal cells that support tumor growth. Changes in extracellular matrix (ECM), abnormal vasculature, hypoxia, and inflammation have been reported to promote tumor aggressiveness that could be exacerbated by prior RT. Prior radiation may have long-term impacts on microglia and brain-infiltrating monocytes, leading to lasting alterations in cytokine signaling and ECM. Tumor-promoting CNS injury responses are recapitulated in the tumor microenvironment and augmented following prior radiation, impacting cell phenotype, proliferation, and infiltration in the CNS. Since RT is vital to GBM management, but substantially alters the tumor microenvironment, we here review challenges, knowledge gaps, and therapeutic opportunities relevant to targeting pro-tumorigenic features of the GBM microenvironment. We suggest that insights from RT-induced changes in the tumor microenvironment may provide opportunities to target mechanisms, such as cellular senescence, that may promote GBM aggressiveness amplified in previously radiated microenvironment.

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New clues in the malignant progression of glioblastoma: can thioredoxin system play a role?

Cited by 8 publications

References 15 publications

Thioredoxin System Protein Expression Is Associated with Poor Clinical Outcome in Adult and Paediatric Gliomas and Medulloblastomas

Thioredoxin System Protein Expression Is Associated with Poor Clinical Outcome in Adult and Paediatric Gliomas and Medulloblastomas

Increased expression of ubiquitin C-terminal hydrolase L1 in astrocytomas of ascending grades

Radiation-Induced Alterations in the Recurrent Glioblastoma Microenvironment: Therapeutic Implications

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