Basal oxidative stress ratio of head and neck squamous cell carcinomas correlates with nodal metastatic spread in patients under therapy

Dequanter, Didier; Dok, Rüveyda; Nuyts, Sandra

doi:10.2147/ott.s118980

Cited by 24 publications

(14 citation statements)

References 11 publications

(16 reference statements)

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“…In line with previous publications, we believe that parameters of oxidative stress could offer useful potential markers ( 3 , 4 ). Previously, we confirmed this hypothesis by demonstrating that a significant redox imbalance in head and neck cancer patients could offer a prognostic value ( 14 ).…”

Section: Discussionsupporting

confidence: 52%

Prognostic Significance of Glutathione Peroxidase Levels (GPx1) in Head and Neck Cancers

et al. 2017

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IntroductionTo date, no reliable prognostic biological marker for all squamous cell carcinoma located in different subsites of the head and neck region has been identified and used in daily routine. In line with our previous studies, in which we showed a role of glutathione and associated enzymes as potential biological markers, we investigated the relationship between GPx1 and prognosis of head and neck squamous cell carcinoma.MethodsThe association between GPx1 and patient and tumor related factors were investigated in 87 pretreatment biopsies from head and neck cancer patients treated by (chemo)radiation. Moreover, the influence of GPx1 expression on outcome parameters was assessed.ResultsA significant difference was found in the T-stage between the low and high-expressing GPx1 groups. About 75% of the T3–T4 tumors were considered GPx1 low-expressing tumors, while low GPx1 expression was only seen in 25% of the T1–T2 tumors. There was also a significant difference found between the groups when looking at the different tumor sites. Local control, locoregional control, disease-free survival, and overall survival were the same in both groups. All these results indicate that GPx1 expression does not influence the radiotherapy response nor survival.

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Section: Discussionsupporting

confidence: 52%

Prognostic Significance of Glutathione Peroxidase Levels (GPx1) in Head and Neck Cancers

et al. 2017

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“…A recent study, for instance, found a correlation between metastatic spread and basal ROS levels. (1121) Indeed, ROS elevation assists several steps within the advanced oncogenic program, including angiogenesis [in part through stabilizing hypoxia inducible factor (HIF), (1122) avoidance of apoptosis,(1123) and metastasis(1124,1125)]. Several studies link elevated ROS levels to increased disease progression and poor clinical outcomes.…”

Section: Res/ros Signaling In Disease and Therapeutic Interventionsmentioning

confidence: 99%

Redox Signaling by Reactive Electrophiles and Oxidants

et al. 2018

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The concept of cell signaling in the context of nonenzyme-assisted protein modifications by reactive electrophilic and oxidative species, broadly known as redox signaling, is a uniquely complex topic that has been approached from numerous different and multidisciplinary angles. Our Review reflects on five aspects critical for understanding how nature harnesses these noncanonical post-translational modifications to coordinate distinct cellular activities: (1) specific players and their generation, (2) physicochemical properties, (3) mechanisms of action, (4) methods of interrogation, and (5) functional roles in health and disease. Emphasis is primarily placed on the latest progress in the field, but several aspects of classical work likely forgotten/lost are also recollected. For researchers with interests in getting into the field, our Review is anticipated to function as a primer. For the expert, we aim to stimulate thought and discussion about fundamentals of redox signaling mechanisms and nuances of specificity/selectivity and timing in this sophisticated yet fascinating arena at the crossroads of chemistry and biology.

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“…In line with our results, recent data have shown that HNSCC patients with lower oxidative stress had a lower risk of local and regional recurrence of tumor after treatment, suggesting a more aggressive behavior of tumors with high oxidative stress. 50 The efficiency of fundamental DNA repair mechanisms, namely NER and DSB repair, were also evaluated. NER eliminates a broad spectrum of DNA lesions, including those produced by ROS and DNA adducts formed by tobacco smoking and cancer therapeutic drugs such as cisplatin.…”

Section: Discussionmentioning

confidence: 99%

The DNA damage response network in the treatment of head and neck squamous cell carcinoma

et al. 2021

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Background: We sought to determine whether DNA damage response (DDR)-related aberrations predict therapeutic benefit in cisplatin-treated head and neck squamous cell carcinoma (HNSCC) patients and how DDR pathways are modulated after treatment with olaparib alone or in combination with cisplatin or durvalumab. Patients and methods: Oxidative stress, abasic sites and DDR-related parameters, including endogenous DNA damage, DNA repair mechanisms and apoptosis rates, were evaluated in HNSCC cell lines and peripheral blood mononuclear cells from 46 healthy controls (HC) and 70 HNSCC patients at baseline and following treatment with cisplatincontaining chemoradiation or nivolumab or enrolled in the OPHELIA phase II trial (NCT02882308; olaparib alone, olaparib plus cisplatin, olaparib plus durvalumab). Results: HNSCC patients at diagnosis exhibited deregulated DDR-related parameters and higher levels of oxidative stress and abasic sites compared with HC (all P < 0.05). Accordingly, nucleotide excision repair (NER; ERCC1, ERCC2/XPD, XPA, XPC) and base excision repair (APEX1, XRCC1) genes were downregulated in patients versus HC whereas double-strand breaks repair (MRE11A, RAD50, RAD51, XRCC2) and mismatch repair (MLH1, MSH2, MSH3) genes were overexpressed. Corresponding results were obtained in cell lines (all P < 0.001). Excellent correlations were observed between individual ex vivo and in vivo/therapeutic results, with cisplatin non-responders showing higher levels of endogenous DNA damage, augmented oxidative stress and abasic sites, increased NER capacities and reduced apoptosis than responders (all P < 0.05). Also, longer progression-free survival correlated with lower NER capacity (P ¼ 0.037) and increased apoptosis (P ¼ 0.029). Interestingly, treatment with olaparib-containing regimens results in the accumulation of cytotoxic DNA damage and exerts an extra antitumor effect by elevating oxidative stress (all P < 0.05). Nivolumab induced no significant changes in the DDR parameters examined. Conclusions: Aberrations in DDR signals are implicated in the response to HNSCC chemotherapy and can be exploited as novel therapeutic targets, sensitive/effective non-invasive biomarkers as well as for the design of novel clinical trials.

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Basal oxidative stress ratio of head and neck squamous cell carcinomas correlates with nodal metastatic spread in patients under therapy

Cited by 24 publications

References 11 publications

Prognostic Significance of Glutathione Peroxidase Levels (GPx1) in Head and Neck Cancers

Prognostic Significance of Glutathione Peroxidase Levels (GPx1) in Head and Neck Cancers

Redox Signaling by Reactive Electrophiles and Oxidants

The DNA damage response network in the treatment of head and neck squamous cell carcinoma

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