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      Could circulating biomarkers of nitrosative stress and protein glycoxidation be useful in patients with gastric cancer?

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          Abstract

          Background

          Nitrosative stress leads to protein glycoxidation, but both processes may be strongly related to the cancer development. Therefore, the aim of this study was to assess the nitrosative stress and protein glycoxidation products in patients with gastric cancer in comparison with healthy controls. We are also the first to evaluate the diagnostic utility of nitrosative stress and protein glycoxidation markers in gastric cancer patients in respect to histopathological classifications (TNM, Lauren’s and Goseki’s classification) and histopathological parameters such as histological type, histological differentiation grade, presence of vascular or neural invasion, desmoplasia and Helicobacter pylori infection.

          Methods

          The study included 50 patients with gastric cancer and 50 healthy controls matched for sex and age. Nitrosative stress parameters and protein glycoxidation products were measured colorimetrically/fluorometrically in plasma or serum samples. Student’s t-test or Mann-Whitney U-test were used for statistical analysis.

          Results

          NO, S-nitrosothiols, nitrotyrosine, kynurenine, N-formylkynurenine, dityrosine, AGE and Amadori products were significantly increased whereas tryptophan fluorescence was decreased in patients with gastric cancer compared to the healthy control. Nitrosative stress and glycoxidation products may be useful in diagnosis of gastric cancer because they differentiate patients with gastric cancer from healthy individuals with high sensitivity and specificity. Some of the determined parameters are characterised by high AUC value in differentiation of GC patients according to the histopathological parameters.

          Conclusions

          Gastric cancer is associated with enhanced circulating nitrosative stress and protein glycation. Although further research on a tissue model is needed, plasma/serum biomarkers may be dependent on tumour size, histological type, tumour invasion depth, presence of lymph node and distant metastasis, vascular and neural invasion and Helicobacter pylori infection. Thus, circulating biomarkers of nitrosative stress/protein glycoxidation may have potential diagnostic significance in gastric cancer patients.

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          Most cited references56

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          Global Burden of 5 Major Types Of Gastrointestinal Cancer

          There were an estimated 4.8 million new cases of gastrointestinal (GI) cancers and 3.4 million related deaths, worldwide, in 2018. GI cancers account for 26% of the global cancer incidence and 35% of all cancer-related deaths. We investigated the global burden from the 5 major GI cancers, as well as geographic and temporal trends in cancer-specific incidence and mortality.
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            • Record: found
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            • Article: not found

            Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond

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              • Record: found
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              • Article: not found

              Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases.

              Reactive oxygen species (ROS) are generated as by-products of normal cellular metabolic activities. Superoxide dismutase, glutathione peroxidase, and catalase are the enzymes involved in protecting cells from the damaging effects of ROS. ROS are produced in response to ultraviolet radiation, cigarette smoking, alcohol, nonsteroidal anti-inflammatory drugs, ischemia-reperfusion injury, chronic infections, and inflammatory disorders. Disruption of normal cellular homeostasis by redox signaling may result in cardiovascular, neurodegenerative diseases and cancer. ROS are produced within the gastrointestinal (GI) tract, but their roles in pathophysiology and disease pathogenesis have not been well studied. Despite the protective barrier provided by the mucosa, ingested materials and microbial pathogens can induce oxidative injury and GI inflammatory responses involving the epithelium and immune/inflammatory cells. The pathogenesis of various GI diseases including peptic ulcers, gastrointestinal cancers, and inflammatory bowel disease is in part due to oxidative stress. Unraveling the signaling events initiated at the cellular level by oxidative free radicals as well as the physiological responses to such stress is important to better understand disease pathogenesis and to develop new therapies to manage a variety of conditions for which current therapies are not always sufficient.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                12 July 2023
                2023
                : 13
                : 1213802
                Affiliations
                [1] 1 Department of Clinical Laboratory Diagnostics, Medical University of Bialystok , Bialystok, Poland
                [2] 2 Department of General Pathomorphology, Medical University of Bialystok , Bialystok, Poland
                [3] 3 2nd Clinical Department of General and Gastroenterological Surgery, Medical University of Bialystok , Bialystok, Poland
                [4] 4 Department of Restorative Dentistry, Croydon University Hospital , Croydon, United Kingdom
                [5] 5 Independent Laboratory of Experimental Dentistry, Medical University of Bialystok , Bialystok, Poland
                [6] 6 Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok , Bialystok, Poland
                Author notes

                Edited by: Reza Alizadeh-Navaei, Mazandaran University of Medical Sciences, Iran

                Reviewed by: Kamendra Kumar, Georgetown University, United States; Ekaterina Gubareva, N.N. Petrov National Medical Research Center of Oncology, Russia; Koraljka Gall Troselj, Rudjer Boskovic Institute, Croatia

                *Correspondence: Justyna Dorf, justyna.dorf@ 123456umb.edu.pl
                Article
                10.3389/fonc.2023.1213802
                10369187
                9da94070-bcd0-48bd-8fac-adaae602d768
                Copyright © 2023 Dorf, Pryczynicz, Matowicka-Karna, Zaręba, Żukowski, Zalewska and Maciejczyk

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 April 2023
                : 23 June 2023
                Page count
                Figures: 5, Tables: 5, Equations: 0, References: 56, Pages: 15, Words: 7479
                Funding
                Funded by: Uniwersytet Medyczny w Bialymstoku , doi 10.13039/501100005297;
                Award ID: SUB/1/DN/22/001/2209, SUB/1/DN/22/005/2209
                The study was supported with grants from the Medical University of Bialystok, Poland (grant numbers: SUB/1/DN/22/001/2209; SUB/1/DN/22/005/2209). JD and JM-K received research support from the Medical University of Bialystok, Poland.
                Categories
                Oncology
                Original Research
                Custom metadata
                Gastrointestinal Cancers: Gastric and Esophageal Cancers

                Oncology & Radiotherapy
                gastric cancer,reactive nitrogen species,nitric oxide,glycoxidation,nitrosative and oxidative stress

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