Biomarkers of oxidative stress and smoking in cancer patients

Burlakova, E. B.; Zhizhina, G. P.; Gurevich, S. M.; Fatkullina, L. D.; Kozachenko, A. I.; Nagler, L. G.; Заварыкина, Т. М.; Кащеев, В. В.

doi:10.4103/0973-1482.63569

Cited by 31 publications

(9 citation statements)

References 36 publications

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“…It is known that smoking enforces oxidative stress triggering a series of events to follow, resulting in tumor. [33][34][35] MIEN1 has a redox motif and has previously been classified as a selenoprotein in the Rdx thioredoxin family with glutathione peroxidase 1 as its target. 36 The role of glutathione peroxidases is linked to reducing free radicals and thus the oxidative stress in the cells, leading to an inverse correlation between oxidative stress and the glutathione peroxidases.…”

Section: Discussionmentioning

confidence: 99%

MIEN1 promotes oral cancer progression and implicates poor overall survival

Rajendiran

Kpetemey

Maji

et al. 2015

Cancer Biology & Therapy

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Abbreviations: CRS, current reformed smoker; CS, current smoker; GFP, green fluorescent protein; HNSCC, head and neck squamous cell carcinoma; MIEN1, migration and invasion enhancer 1; MMP-9, matrix metallopeptidase 9; NF-kB, nuclear factor kappalight-chain-enhancer of activated B cells; OSCC, oral squamous cell carcinoma; siRNA, small interfering RNA; TCGA, the cancer genome atlas; uPA, urokinase plasminogen activator; VEGF, vascular endothelial growth factorOral squamous cell carcinoma is a highly malignant tumor with the potential to invade local and distant sites and promote lymph node metastasis. Major players underlying the molecular mechanisms behind tumor progression are yet to be fully explored. Migration and invasion enhancer 1 (MIEN1), a novel protein overexpressed in various cancers, facilitates cell migration and invasion. In the present study we investigated the expression and role of MIEN1 in oral cancer progression using an in vitro model, patient derived oral tissues and existing TCGA data. Expression analysis using immortalized normal and cancer cells demonstrated increased expression of MIEN1 in cancer. Assays performed after MIEN1 knockdown in OSC-2 cells showed decreased migration, invasion and filopodia formation; while MIEN1 overexpression in DOK cells increased these characteristics and also up-regulated some Akt/NF-kB effectors, thereby suggesting an important role for MIEN1 in oral cancer progression. Immunohistochemical staining and analyses of oral tissue specimens, collected from patients over multiple visits, revealed significantly more staining in severe dysplasia and squamous cell carcinoma compared to mildly dysplastic or hyperplastic tissues. Finally, this was corroborated with the TCGA dataset, where MIEN1 expression was not only higher in intermediate and high grade cancer with significantly lower survival but also correlated with smoking. In summary, we demonstrate that MIEN1 expression not only positively correlates with oral cancer progression but also seems to be a critical molecular determinant in migration and invasion of oral cancer cells, thereby, playing a possible role in their metastatic dissemination.

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Section: Discussionmentioning

confidence: 99%

MIEN1 promotes oral cancer progression and implicates poor overall survival

Rajendiran

Kpetemey

Maji

et al. 2015

Cancer Biology & Therapy

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“…Due to the direct surface exposure, cigarette smoking triggers an inflammatory response in human lung and causes chronic obstructive pulmonary disease (COPD) [85], which has been shown to possess significant abnormalities in inflammatory pathways [86–89]. Smokers are known to have elevated levels of oxidative stress [11, 47], which is increasingly linked to cancer and neurological diseases [90, 91]. Cigarette smoke may induce oxidative stress by several mechanisms [11, 47]: (1) it contains oxidizing compounds and ROS; (2) the ROS-generating redox cycling by quinone-hydroquinone complex as well as PAH quinones and their corresponding catechols; (3) smoking may weaken the antioxidant defense system.…”

Section: Formation and Repair Of Bulky Dna Adducts By Tobacco Carcmentioning

confidence: 99%

“…Smokers are known to have elevated levels of oxidative stress [11, 47], which is increasingly linked to cancer and neurological diseases [90, 91]. Cigarette smoke may induce oxidative stress by several mechanisms [11, 47]: (1) it contains oxidizing compounds and ROS; (2) the ROS-generating redox cycling by quinone-hydroquinone complex as well as PAH quinones and their corresponding catechols; (3) smoking may weaken the antioxidant defense system. The elevated oxidative stress in smokers is accompanied by lipid peroxidation (LPO) [11] which results from reactions of reduced oxygen species with polyunsaturated fatty acids (PUFAs).…”

Section: Formation and Repair Of Bulky Dna Adducts By Tobacco Carcmentioning

confidence: 99%

“…There is also evidence that a high level of bulky DNA adducts in tissues, such as those caused by PAHs and vinyl chloride (VC), is associated with an increased risk of tumor in humans and animals [40, 44–46]. It should be pointed out that tobacco smoke also produces reactive oxygen species (ROS) and induces oxidative stress [11, 47]. Those lesions that arise directly from ROS attack of a base (e.g., 8-oxoG) or deoxyribose (e.g., base propenals) [48, 49] could also play a role in tobacco carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Formation and Repair of Tobacco Carcinogen-Derived Bulky DNA Adducts

Hang

2010

Journal of Nucleic Acids

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DNA adducts play a central role in chemical carcinogenesis. The analysis of formation and repair of smoking-related DNA adducts remains particularly challenging as both smokers and nonsmokers exposed to smoke are repetitively under attack from complex mixtures of carcinogens such as polycyclic aromatic hydrocarbons and N-nitrosamines. The bulky DNA adducts, which usually have complex structure, are particularly important because of their biological relevance. Several known cellular DNA repair pathways have been known to operate in human cells on specific types of bulky DNA adducts, for example, nucleotide excision repair, base excision repair, and direct reversal involving O6-alkylguanine DNA alkyltransferase or AlkB homologs. Understanding the mechanisms of adduct formation and repair processes is critical for the assessment of cancer risk resulting from exposure to cigarette smoke, and ultimately for developing strategies of cancer prevention. This paper highlights the recent progress made in the areas concerning formation and repair of bulky DNA adducts in the context of tobacco carcinogen-associated genotoxic and carcinogenic effects.

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“…Voluntary and non-voluntary (second hand smoke) contributes to ~90% of lung cancer cases [4, 5]. Tobacco induced carcinogenesis occurs through various mechanisms including formation of bulky DNA adducts [4], induction of inflammation [6], increased oxidative stress [7] and activation of diverse signaling pathways [6]. Furthermore, environmental and occupational respiratory carcinogens such as asbestos may interact with cigarette smoke and increase the probability of developing lung cancer [8].…”

Section: Introductionmentioning

confidence: 99%

Drug Resistance Mechanisms in Non-Small Cell Lung Carcinoma

Wangari-Talbot

Hopper-Borge

2013

J. Can. Res. Updates

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Lung cancer is the most commonly diagnosed cancer in the world. “Driver” and “passenger” mutations identified in lung cancer indicate that genetics play a major role in the development of the disease, progression, metastasis and response to therapy. Survival rates for lung cancer treatment have remained stagnant at ~15% over the past 40 years in patients with disseminated disease despite advances in surgical techniques, radiotherapy and chemotherapy. Resistance to therapy; either intrinsic or acquired has been a major hindrance to treatment leading to great interest in studies seeking to understand and overcome resistance. Genetic information gained from molecular analyses has been critical in identifying druggable targets and tumor profiles that may be predictors of therapeutic response and mediators of resistance. Mutated or overexpressed epidermal growth factor receptor (EGFR) and translocations in the echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) genes (EML4-ALK) are examples of genetic aberrations resulting in targeted therapies for both localized and metastatic disease. Positive clinical responses have been noted in patients harboring these genetic mutations when treated with targeted therapies compared to patients lacking these mutations. Resistance is nonetheless a major factor contributing to the failure of targeted agents and standard cytotoxic agents. In this review, we examine molecular mechanisms that are potential drivers of resistance in non-small cell lung carcinoma, the most frequently diagnosed form of lung cancer. The mechanisms addressed include resistance to molecular targeted therapies as well as conventional chemotherapeutics through the activity of multidrug resistance proteins.

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Biomarkers of oxidative stress and smoking in cancer patients

Cited by 31 publications

References 36 publications

MIEN1 promotes oral cancer progression and implicates poor overall survival

MIEN1 promotes oral cancer progression and implicates poor overall survival

Formation and Repair of Tobacco Carcinogen-Derived Bulky DNA Adducts

Drug Resistance Mechanisms in Non-Small Cell Lung Carcinoma

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