Intratumoral hemorrhage-related differences in the expression of vascular endothelial growth factor, basic fibroblast growth factor and thioredoxin reductase 1 in human glioblastoma

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

doi:10.3892/mco.2016.974

Cited by 9 publications

(7 citation statements)

References 19 publications

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“…The patient number in this study compares well against others that have sought to examine Trx system in GBM, i.e. the studies from Kaya et al [30] and Kemerdere et al [21] which included 20 and 27 GBM patients, respectively.…”

Section: Discussionmentioning

confidence: 70%

“…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]. The number of adult GBM patients included in the current study (n = 18) could be regarded as being rather small however the low incidence of this tumour type should be borne in mind.…”

Section: Discussionmentioning

confidence: 98%

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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: 70%

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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“…In mouse lung cancer cells, KO in mitochondrial TrxR alters cell redox status, stabilizes prolyl hydroxylases, and inhibits HIF-1 cascade, suppressing tumor angiogenesis [109]. In the case of humans, in glioblastomas with intratumoral hemorrhage there is an increase in the expression of VEGF and TrxR1, which can be related to an increase in tumor angiogenesis [110].…”

Section: The Thioredoxin Systemmentioning

confidence: 99%

Control of tumor angiogenesis and metastasis through modulation of cell redox state

Serrano

Delgado

Medina

2020

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Redox reactions pervade all biology. The control of cellular redox state is essential for bioenergetics and for the proper functioning of many biological functions. This review traces a timeline of findings regarding the connections between redox and cancer. There is ample evidence of the involvement of cellular redox state on the different hallmarks of cancer. Evidence of the control of tumor angiogenesis and metastasis through modulation of cell redox state is reviewed and highlighted.

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“…Glioblastoma multiforme (GBM) is the most aggressive and common form of glioma, being responsible for 3–4% of all cancer-related deaths ( Carlsson et al, 2014 ; Kaya et al, 2016 ). The risk of prevalence increases with age, being more common in people aged 60–79 years ( Kyani et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Thioredoxin Reductase Inhibitors as Potential Antitumors: Mercury Compounds Efficacy in Glioma Cells

Pires

Bramatti

Aschner

et al. 2022

Front. Mol. Biosci.

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Glioblastoma multiforme (GBM) is the most aggressive and common form of glioma. GBM, like many other tumors, expresses high levels of redox proteins, such as thioredoxin (Trx) and thioredoxin reductase (TrxR), allowing tumor cells to cope with high levels of reactive oxygen species (ROS) and resist chemotherapy and radiotherapy. Thus, tackling the activity of these enzymes is a strategy to reduce cell viability and proliferation and most importantly achieve tumor cell death. Mercury (Hg) compounds are among the most effective inhibitors of TrxR and Trx due to their high affinity for binding thiols and selenols. Moreover, organomercurials such as thimerosal, have a history of clinical use in humans. Thimerosal effectively crosses the blood–brain barrier (BBB), thus reaching effective concentrations for the treatment of GBM. Therefore, this study evaluated the effects of thimerosal (TmHg) and its metabolite ethylmercury (EtHg) over the mouse glioma cell line (GL261), namely, the inhibition of the thioredoxin system and the occurrence of oxidative cellular stress. The results showed that both TmHg and EtHg increased oxidative events and triggered cell death primarily by apoptosis, leading to a significant reduction in GL261 cell viability. Moreover, the cytotoxicity of TmHg and ETHg in GL261 was significantly higher when compared to temozolomide (TMZ). These results indicate that EtHg and TmHg have the potential to be used in GBM therapy since they strongly reduce the redox capability of tumor cells at exceedingly low exposure levels.

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Intratumoral hemorrhage-related differences in the expression of vascular endothelial growth factor, basic fibroblast growth factor and thioredoxin reductase 1 in human glioblastoma

Cited by 9 publications

References 19 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

Control of tumor angiogenesis and metastasis through modulation of cell redox state

Thioredoxin Reductase Inhibitors as Potential Antitumors: Mercury Compounds Efficacy in Glioma Cells

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