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Asadikaram G, Ashrafi MR, Darvish Moghaddam S, Abolhassani M, Bagheri F. Association of high organochlorine pesticide serum levels with oxidative stress in intestinal metaplasia and gastric cancer. Heliyon 2025; 11:e41599. [PMID: 39897791 PMCID: PMC11783381 DOI: 10.1016/j.heliyon.2024.e41599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 11/24/2024] [Accepted: 12/30/2024] [Indexed: 02/04/2025] Open
Abstract
It has been revealed that certain organochlorine pesticides may increase the risk of gastric cancer incidence among farm workers. This research aimed to assay levels of 7 different organochlorine pesticides in the serum of functional dyspepsia, intestinal metaplasia and gastric cancer patients, along with measuring oxidative stress parameters compared to the control group and their associations. The levels of organochlorine pesticides in the serum of gastric cancer (n = 34), intestinal metaplasia (n = 8), functional dyspepsia patients (n = 48) and control group (n = 46), were measured by gas chromatography equipment. Oxidative stress parameters and erythrocyte acetylcholine esterase activity were also measured in these individuals. The levels of some organochlorine pesticides in the serum of gastric cancer patients were significantly higher than those in the control group. Moreover, the profiles of organochlorine pesticide concentrations were different in gastric cancer, intestinal metaplasia and functional dyspepsia patients. Overall, oxidant parameters were significantly higher in gastric cancer and intestinal metaplasia patients than those in functional dyspepsia patients and the control group, except in the case of malondialdehyde. The antioxidant and acetylcholine esterase enzyme activities were significantly higher in the control group than in other groups. Our results showed that progression from functional dyspepsia towards intestinal metaplasia and gastric cancer was associated with elevations in organochlorine pesticide serum levels, which had an association with the induction of oxidative stress and the reduction of antioxidant and acetylcholine esterase enzyme activities.
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Affiliation(s)
- Gholamreza Asadikaram
- Applied Cellular and Molecular Research Center, Kerman University of Medical Sciences, Kerman, Iran
- Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
- Department of Clinical Biochemistry, Afzalipur School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohammad Reza Ashrafi
- Applied Cellular and Molecular Research Center, Kerman University of Medical Sciences, Kerman, Iran
- Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
- Department of Clinical Biochemistry, Afzalipur School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Sodaif Darvish Moghaddam
- Gastroenterology and Hepatology Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Moslem Abolhassani
- Applied Cellular and Molecular Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Fatemeh Bagheri
- Pathology and Stem Cell Research Center, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
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Zhang X, Chen J, Sheng X, Ding CF, Yan Y. Preparation and characterization of a biomimetic honeycomb cross-linked chitosan membrane and its application in the serum of gastric cancer patients. Int J Biol Macromol 2024; 279:135367. [PMID: 39244117 DOI: 10.1016/j.ijbiomac.2024.135367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 08/23/2024] [Accepted: 09/04/2024] [Indexed: 09/09/2024]
Abstract
Chitosan, as a biological macromolecule with excellent biocompatibility, has great potential for application in immobilized metal affinity chromatography (IMAC) strategies. In-depth analysis of low-abundance phosphopeptides in organisms can help reveal the pathological mechanisms of diseases. Here, we developed an IMAC material based on a biomimetic honeycomb chitosan membrane. The material demonstrates excellent biocompatibility, good hydrophilicity, and strong metal chelating capacity, which collectively confer outstanding enrichment properties. The material has high sensitivity (0.05 fmol), great selectivity (1:2000), excellent cycling stability (at least 10 cycles) and acid-base stability. In addition, the material was employed in human serum, successfully enriching 129 phosphopeptides from the serum of gastric cancer patients and 146 phosphopeptides from healthy controls. Sequence logo suggests a potential association between gastric cancer and glutamine. Ultimately, an in-depth gene ontology analysis was carried out on the phosphopeptides that were enriched in the serum samples. Compared to normal controls, our results demonstrated dysregulated expression of biological process, cellular component, and molecular function in gastric cancer patients. This suggests that the disease involves, such as blood coagulation pathways, cholesterol metabolism, and heparin binding. All experimental outcomes converge to demonstrate the substantial promise of the material for applications within proteomics research.
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Affiliation(s)
- Xiaoya Zhang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, School of Materials Science and Chemical Engineering, Ningbo University, Ningbo 315211, PR China
| | - Jiakai Chen
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, School of Materials Science and Chemical Engineering, Ningbo University, Ningbo 315211, PR China
| | - Xiuqin Sheng
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, School of Materials Science and Chemical Engineering, Ningbo University, Ningbo 315211, PR China
| | - Chuan-Fan Ding
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, School of Materials Science and Chemical Engineering, Ningbo University, Ningbo 315211, PR China.
| | - Yinghua Yan
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, School of Materials Science and Chemical Engineering, Ningbo University, Ningbo 315211, PR China.
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Koike M, Nagao M, Iwase Y, Kaneko K, Ishijima M, Nojiri H. Clinical Efficacy of Melon GliSODin ® for the Treatment of Aging-Related Dysfunction in Motor Organs-A Double Blind, Randomized Placebo-Controlled Study. J Clin Med 2022; 11:2747. [PMID: 35628874 PMCID: PMC9143343 DOI: 10.3390/jcm11102747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 04/29/2022] [Accepted: 05/05/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Locomotive syndrome is a concept proposed in Japan involving decreased mobility due to osteoarthritis, osteoporosis, and sarcopenia. This double-blind, randomized study aimed to investigate the effects of superoxide dismutase (SOD)-rich melon extract (Melon GliSODin®) on locomotive syndrome. METHODS For 6 months, we administered oral Melon GliSODin® (500.4 mg/day) or a placebo to 24 and 22 women, respectively (aged 50-80 years), with knee or lower back discomfort or pain. Using baseline and 6-month data, changes in the Verbal Rating Scale and in subjective symptoms (determined using the Japanese Knee Osteoarthritis Measure, Locomo 25, the Roland-Morris Disability questionnaire, and the Chalder Fatigue Scale) were assessed, along with various oxidative markers, antioxidants, inflammatory markers, renal and liver function biochemical markers, bone metabolism markers, body composition, and motor function. RESULTS Oral Melon GliSODin® administration tended to be associated with a larger improvement in subjective symptom scores, a reduction in oxidative markers (malondialdehyde and diacron reactive oxygen metabolites) and tumor necrosis factor-α, and a significant increase in non-fat mass between baseline and 6 months. However, no statistically significant differences were observed between the groups for outcomes at 6 months. CONCLUSIONS Melon GliSODin® tended to improve the subjective symptoms of participants who had knee or lower back pain or discomfort. Melon GliSODin® administration may help to prevent the progression of locomotive syndrome. Future studies involving larger sample sizes and more stringent randomization protocols are needed to determine differences between the placebo and Melon GliSODin® groups.
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Affiliation(s)
- Masato Koike
- Department of Orthopaedic Surgery, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo 136-0075, Japan; (M.K.); (Y.I.)
| | - Masashi Nagao
- Department of Orthopaedic Surgery, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; (M.N.); (K.K.); (M.I.)
- Department of Orthopaedic Surgery, Medical Technology Innovation Center, Clinical Research & Trial Center, Graduate School of Health and Sports Science, Juntendo University, Tokyo 113-8421, Japan
| | - Yoshiyuki Iwase
- Department of Orthopaedic Surgery, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo 136-0075, Japan; (M.K.); (Y.I.)
| | - Kazuo Kaneko
- Department of Orthopaedic Surgery, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; (M.N.); (K.K.); (M.I.)
| | - Muneaki Ishijima
- Department of Orthopaedic Surgery, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; (M.N.); (K.K.); (M.I.)
| | - Hidetoshi Nojiri
- Department of Orthopaedic Surgery, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo 136-0075, Japan; (M.K.); (Y.I.)
- Department of Orthopaedic Surgery, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; (M.N.); (K.K.); (M.I.)
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Qiu W, Jiang J, Zhan Z, Huang L, Deng J, Ye J, Li G, Liao K, Zhang H, Ding Y, Yuan Y, Zheng R. Prognostic impact of pretreatment serum superoxide dismutase activity in patients with locoregionally advanced nasopharyngeal carcinoma. Int J Biol Markers 2022; 37:21-30. [PMID: 35099330 DOI: 10.1177/17246008221075042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Abstract
PURPOSE To evaluate the prognostic effect of pretreatment serum superoxide dismutase (SOD) activity in locoregionally advanced nasopharyngeal carcinoma. METHODS A total of 498 patients diagnosed with stage III-IVA nasopharyngeal carcinoma between January 2013 and December 2016 were involved in this study. The X-tile program was used to determine the cut-off value of pretreatment serum SOD activity based on disease-free survival. Kaplan-Meier methods and Cox proportional hazards models were used to evaluate the impact of serum SOD levels on survival outcomes. The receiver operating characteristic (ROC) curve analysis was used to compare the prognostic value of clinical stage, pretreatment serum SOD level, and the combination of them regarding disease-free survival. RESULTS Based on the X-tile plot, the optimal cutoff value of pretreatment serum SOD activity for disease-free survival was 146.0U/mL. As a dichotomous variable, SOD was significantly higher in non-keratinizing differentiated disease (P = 0.027) and early T stage (P = 0.011). Compared with the lower subset, higher SOD activity predicted an inferior 3-year rates of overall survival (84.6 vs. 94.7%, P < 0.001), distant metastasis-free survival (78.3 vs. 92.8%, P < 0.001) and disease-free survival (78.2 vs. 92.8%, P < 0.001). Multivariate analysis verified that the SOD activity was an independent prognostic indicator to predict distant metastasis, disease progression, and death. The area under the ROC curve (AUC) of the combination was superior to that of clinical stage or SOD alone for disease-free survival (both P < 0.01). CONCLUSION Serological SOD activity before treatment is an important prognostic indicator for patients with stage III-IV non-metastatic nasopharyngeal carcinoma undergoing chemoradiation therapy.
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Affiliation(s)
- Wenze Qiu
- Department of Radiation Oncology, 198153Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, PR China
| | - Jiali Jiang
- Health Ward, 74669Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, PR China
| | - Zejiang Zhan
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, 71067Sun Yat-sen University Cancer Center, Guangzhou, PR China.,Department of Nasopharyngeal Carcinoma, 71067Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Laiji Huang
- Department of Radiation Oncology, 198153Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, PR China
| | - Jin Deng
- Department of Radiation Oncology, 198153Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, PR China
| | - Jiacai Ye
- Department of Radiation Oncology, 198153Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, PR China
| | - Guo Li
- Department of Radiation Oncology, 198153Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, PR China
| | - Kai Liao
- Department of Radiation Oncology, 198153Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, PR China
| | - Huanhuan Zhang
- Department of Radiation Oncology, 198153Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, PR China
| | - Yan Ding
- Department of Radiation Oncology, 198153Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, PR China
| | - Yawei Yuan
- Department of Radiation Oncology, 198153Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, PR China
| | - Ronghui Zheng
- Department of Radiation Oncology, 198153Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, PR China
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Li J, Lei J, He L, Fan X, Yi F, Zhang W. Evaluation and Monitoring of Superoxide Dismutase (SOD) Activity and its Clinical Significance in Gastric Cancer: A Systematic Review and Meta-Analysis. Med Sci Monit 2019; 25:2032-2042. [PMID: 30886134 PMCID: PMC6436205 DOI: 10.12659/msm.913375] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Background This systematic review of the literature and meta-analysis aimed to review the evaluation and monitoring of superoxide dismutase (SOD) activity and its clinical significance in gastric cancer. Material/Methods Systematic review involved searching the PubMed, Embase, Ovid, and the China National Knowledge Infrastructure (CNKI) databases. Search terms included ‘superoxide dismutase,’ and ‘gastric cancer.’ Studies that included measurements of SOD activity in peripheral blood samples in patients with SOD activity compared with healthy controls. The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results Ten controlled clinical studies were identified that included six studies that measured SOD in serum, three in erythrocytes, and one study that measured SOD on whole blood. Meta-analysis, using the standardized mean difference (SMD) and the 95% confidence interval (CI), showed that patients with gastric cancer had significantly decreased SOD activity when compared with the healthy controls (SMD, −0.840; 95% CI, −1.463 to −0.218; p=0.008). Subgroup analysis was conducted on SOD distribution in the blood (erythrocyte: SMD, −1.773; 95% CI, −2.504 to −1.042; p=0.000) (serum SMD, −0.322; 95% CI, −1.006−0.361; p=0.355) (whole blood: SMD, −1.251; 95% CI, −1.731 to −0.771; p=0.000) and for male subjects (SMD, −2.090; 95% CI, −2.725 to −1.456; p<0.001). Conclusions Meta-analysis showed that SOD measurements from blood samples, especially in erythrocytes, had potential as a diagnostic and monitoring parameter in patients with gastric cancer.
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Affiliation(s)
- Jine Li
- Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China (mainland).,Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China (mainland)
| | - Jun Lei
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China (mainland)
| | - Liyun He
- Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China (mainland).,Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China (mainland)
| | - Xiude Fan
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Fengming Yi
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China (mainland)
| | - Wenxiong Zhang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China (mainland)
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Davoodian N, Kadivar A, Ahmadi E, Mohebbi A. Effects of Two Amino Acids on Motion Parameters and Enzymatic Antioxidant Activity of Freeze-Thawed Stallion Spermatozoa. J Equine Vet Sci 2017. [DOI: 10.1016/j.jevs.2017.09.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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Dehkordi AJ, Mohebbi AN, Aslani MR, Ghoreyshi SM. Evaluation of nanoselenium (Nano-Se) effect on hematological and serum biochemical parameters of rat in experimentally lead poisoning. Hum Exp Toxicol 2016; 36:421-427. [DOI: 10.1177/0960327116651124] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The present study was designed to evaluate the effect of nanoselenium (Nano-Se) on hematological and biochemical parameters of rats experimentally intoxicated with lead (Pb). Thirty male rats were randomly divided into six groups as follows: the control, selenite, Nano-Se, Pb group, Pb + selenite, and Pb + Nano-Se groups. After 35 days, blood was collected from rats and hematology and serum biochemical parameters of oxidative stress were measured. The thiobarbituric acid reactive substances (TBARS) level of Pb group was significantly higher than other groups. Also, TBARS level was significantly lower in the Pb + Nano-Se group than Pb + selenite group. The serum superoxide dismutase activities were significantly lower in Pb group than the control, Pb + selenite, and Pb + Nano-Se groups. The catalase activities in the Pb group showed no significant change when compared to other groups. In the Pb group, packed cell volume was lower than the control group. A significant difference was observed between the control group and the Pb, Pb + selenite, and Pb + Nano-Se groups. In the Pb group, the numbers of white blood cell (WBC) decreased in comparison with the control group. Also, there was significant increase in WBC counts in the Pb + Nano-Se and Pb + selenite groups in comparison with Pb group. The number of lymphocytes in the Pb group decreased in comparison with the control group. By comparing the means of the Pb + Nano-Se and Pb + selenite groups together, it was determined that there were significant differences in the lymphocytes and neutrophil counts. In conclusion, usage of selenium compounds particularly Nano-Se particles inhibits the adverse effects of Pb on antioxidant activity and immune system function in the Pb poisoning.
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Affiliation(s)
- A Jafari Dehkordi
- Department of Clinical Science, Veterinary Faculty, Shahrekord University, Shahrekord, Islamic Republic of Iran
| | - AN Mohebbi
- Department of Clinical Science, Veterinary Faculty, Shahrekord University, Shahrekord, Islamic Republic of Iran
| | - MR Aslani
- Department of Clinical Science, Veterinary Faculty, Shahrekord University, Shahrekord, Islamic Republic of Iran
| | - SM Ghoreyshi
- Veterinary Faculty, Shahrekord University, Shahrekord, Islamic Republic of Iran
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Hassanpour H, Khalaji-Pirbalouty V, Nasiri L, Mohebbi A, Bahadoran S. Oxidant and enzymatic antioxidant status (gene expression and activity) in the brain of chickens with cold-induced pulmonary hypertension. INTERNATIONAL JOURNAL OF BIOMETEOROLOGY 2015; 59:1615-1621. [PMID: 25939899 DOI: 10.1007/s00484-015-0968-z] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Revised: 12/21/2014] [Accepted: 01/26/2015] [Indexed: 06/04/2023]
Abstract
To evaluate oxidant and antioxidant status of the brain (hindbrain, midbrain, and forebrain) in chickens with cold-induced pulmonary hypertension, the measurements of lipid peroxidation, protein oxidation, antioxidant capacity, enzymatic activity, and gene expression (for catalase, glutathione peroxidase, and superoxide dismutases) were done. There were high lipid peroxidation/protein oxidation and low antioxidant capacity in the hindbrain of cold-induced pulmonary hypertensive chickens compared to control (P < 0.05). In the hypertensive chickens, superoxide dismutase activity was decreased (forebrain, midbrain, and hindbrain), while catalase activity was increased (forebrain and midbrain) (P < 0.05). Glutathione peroxidase activity did not change. Relative gene expression of catalase and superoxide dismutases (1 and 2) was downregulated, while glutathione peroxidase was upregulated in the brain of the cold-induced pulmonary hypertensive chickens. Probably, these situations in the oxidant and antioxidant status of the brain especially hindbrain may change its function at cardiovascular center and sympathetic nervous system to exacerbate pulmonary hypertension.
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Affiliation(s)
- Hossein Hassanpour
- Department of Basic Sciences, Physiology Division, Faculty of Veterinary Medicine, Shahrekord University, P.O. BOX 115, Saman Road, Shahrekord, Iran.
| | | | - Leila Nasiri
- Department of Biology, Faculty of Science, Shahrekord University, P.O. BOX 115, Saman Road, Shahrekord, Iran
| | - Abdonnaser Mohebbi
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord University, P.O. BOX 115, Saman Road, Shahrekord, Iran
| | - Shahab Bahadoran
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord University, P.O. BOX 115, Saman Road, Shahrekord, Iran
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Subbannayya Y, Mir SA, Renuse S, Manda SS, Pinto SM, Puttamallesh VN, Solanki HS, Manju HC, Syed N, Sharma R, Christopher R, Vijayakumar M, Veerendra Kumar KV, Keshava Prasad TS, Ramaswamy G, Kumar RV, Chatterjee A, Pandey A, Gowda H. Identification of differentially expressed serum proteins in gastric adenocarcinoma. J Proteomics 2015; 127:80-8. [PMID: 25952687 DOI: 10.1016/j.jprot.2015.04.021] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2015] [Revised: 04/14/2015] [Accepted: 04/21/2015] [Indexed: 01/01/2023]
Abstract
UNLABELLED Gastric adenocarcinoma is an aggressive cancer with poor prognosis. Blood based biomarkers of gastric cancer have the potential to improve diagnosis and monitoring of these tumors. Proteins that show altered levels in the circulation of gastric cancer patients could prove useful as putative biomarkers. We used an iTRAQ-based quantitative proteomic approach to identify proteins that show altered levels in the sera of patients with gastric cancer. Our study resulted in identification of 643 proteins, of which 48 proteins showed increased levels and 11 proteins showed decreased levels in serum from gastric cancer patients compared to age and sex matched healthy controls. Proteins that showed increased expression in gastric cancer included inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), Mannose-binding protein C (MBL2), sex hormone-binding globulin (SHBG), insulin-like growth factor-binding protein 2 (IGFBP2), serum amyloid A protein (SAA1), Orosomucoid 1 (ORM1) and extracellular superoxide dismutase [Cu-Zn] (SOD3). We used multiple reaction monitoring assays and validated elevated levels of ITIH4 and SAA1 proteins in serum from gastric cancer patients. BIOLOGICAL SIGNIFICANCE Gastric cancer is a highly aggressive cancer associated with high mortality. Serum-based biomarkers are of considerable interest in diagnosis and monitoring of various diseases including cancers. Gastric cancer is often diagnosed at advanced stages resulting in poor prognosis and high mortality. Pathological diagnosis using biopsy specimens remains the gold standard for diagnosis of gastric cancer. Serum-based biomarkers are of considerable importance as they are minimally invasive. In this study, we carried out quantitative proteomic profiling of serum from gastric cancer patients to identify proteins that show altered levels in gastric cancer patients. We identified more than 50 proteins that showed altered levels in gastric cancer patient sera. Validation in a large cohort of well classified patient samples would prove useful in identifying novel blood based biomarkers for gastric cancers. This article is part of a Special Issue entitled: Proteomics in India.
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Affiliation(s)
- Yashwanth Subbannayya
- Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; Rajiv Gandhi University of Health Sciences, Bangalore 560041, Karnataka, India; Department of Biochemistry, Kidwai Memorial Institute of Oncology, Bangalore 560029, Karnataka, India
| | - Sartaj Ahmad Mir
- Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; Manipal University, Manipal 576 104, Karnataka, India
| | - Santosh Renuse
- Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690525, India
| | - Srikanth S Manda
- Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; Centre of Excellence in Bioinformatics, School of Life Sciences, Pondicherry University, Puducherry 605014, India
| | - Sneha M Pinto
- Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; Manipal University, Manipal 576 104, Karnataka, India
| | | | | | - H C Manju
- Institute of Bioinformatics, International Technology Park, Bangalore 560066, India
| | - Nazia Syed
- Institute of Bioinformatics, International Technology Park, Bangalore 560066, India; Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry 605014, India
| | - Rakesh Sharma
- Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore 560029, Karnataka, India
| | - Rita Christopher
- Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore 560029, Karnataka, India
| | - M Vijayakumar
- Department of Surgery, Kidwai Memorial Institute of Oncology, Bangalore 560029, Karnataka, India
| | - K V Veerendra Kumar
- Department of Surgery, Kidwai Memorial Institute of Oncology, Bangalore 560029, Karnataka, India
| | - T S Keshava Prasad
- Institute of Bioinformatics, International Technology Park, Bangalore 560066, India
| | - Girija Ramaswamy
- Department of Biochemistry, Kidwai Memorial Institute of Oncology, Bangalore 560029, Karnataka, India
| | - Rekha V Kumar
- Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore 560029, Karnataka, India
| | - Aditi Chatterjee
- Institute of Bioinformatics, International Technology Park, Bangalore 560066, India
| | - Akhilesh Pandey
- McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Harsha Gowda
- Institute of Bioinformatics, International Technology Park, Bangalore 560066, India.
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Ma Y, Zhang L, Rong S, Qu H, Zhang Y, Chang D, Pan H, Wang W. Relation between gastric cancer and protein oxidation, DNA damage, and lipid peroxidation. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2013; 2013:543760. [PMID: 24454985 PMCID: PMC3886607 DOI: 10.1155/2013/543760] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Revised: 10/29/2013] [Accepted: 12/01/2013] [Indexed: 12/19/2022]
Abstract
OBJECTS The aim of this study is to evaluate protein oxidation, DNA damage, and lipid peroxidation in patients with gastric cancer and to investigate the relationship between oxidative stress and gastric cancer. METHODS We investigated changes in serum protein carbonyl (PC), advanced oxidation protein products (AOPP), and 3-nitrotyrosine (3-NT) levels, as indicators of protein oxidation, serum 8-hydroxydeoxyguanosine (8-OHdG), as a biomarker of DNA damage, and malondialdehyde (MDA), conjugated diene (CD), 4-hydroxynonenal (4-HNE), and 8-ISO-prostaglandin F2α (8-PGF) in serum, as lipid peroxidation markers in gastric cancer (GC) patients and healthy control. RESULTS Compared with control, a statistically significant higher values of 8-OHdG, PC, AOPP, and 3-NT were observed in the GC patients (P < 0.05). The products of lipid peroxidation, MDA, CD, 4-HNE, and 8-PGF, were significantly lower in the GC patients compared to those of control (P < 0.05). In addition, the products of oxidative stress were similar between the Helicobacter pylori positive and the negative subgroups of GC patients. CONCLUSIONS GC patients were characterized by increased protein oxidation and DNA damage, and decreased lipid peroxidation. Assessment of oxidative stress and augmentation of the antioxidant defense system may be important for the treatment and prevention of gastric carcinogenesis.
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Affiliation(s)
- Yongsheng Ma
- The First Affiliated Hospital of Harbin Medical University, No. 199 Dongdazhi Street, Nangang District, Harbin, Heilongjiang 150001, China
| | - Lin Zhang
- The First Affiliated Hospital of Harbin Medical University, No. 199 Dongdazhi Street, Nangang District, Harbin, Heilongjiang 150001, China
| | - Shengzhong Rong
- Public Health School, Mudanjiang Medical College, No. 3 Tongxiang Street, Aimin District, Mudanjiang, Heilongjiang 157011, China
| | - Hongyan Qu
- The Third Affiliated Hospital of Harbin Medical University, No. 150 Haping Road, Nangang District, Harbin, Heilongjiang 150081, China
| | - Yannan Zhang
- Public Health School, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin, Heilongjiang 150081, China
| | - Dong Chang
- The First Affiliated Hospital of Harbin Medical University, No. 199 Dongdazhi Street, Nangang District, Harbin, Heilongjiang 150001, China
| | - Hongzhi Pan
- Public Health School, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin, Heilongjiang 150081, China
| | - Wenbo Wang
- The First Affiliated Hospital of Harbin Medical University, No. 199 Dongdazhi Street, Nangang District, Harbin, Heilongjiang 150001, China
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Geetha A, Saranya P, Annie Jeyachristy S, Surendran R, Sundaram A. Relevance of non-ceruloplasmin copper to oxidative stress in patients with hepatocellular carcinoma. Biol Trace Elem Res 2009; 130:229-40. [PMID: 19229483 DOI: 10.1007/s12011-009-8338-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2009] [Accepted: 02/03/2009] [Indexed: 01/21/2023]
Abstract
Altered copper homeostasis and oxidative stress have been observed in patients with hepatocellular carcinoma. Non-ceruloplasmin copper, the free form, is a potent pro-oxidant than the protein bound copper. The aim of the present study was to evaluate which form of copper can be correlated with the oxidative stress in the circulation and in the malignant liver tissues of hepatocellular carcinoma patients. Hepatocellular carcinoma patients (grades II and III, n = 18) were enrolled in this study. Serum levels of total, free and bound copper, ceruloplasmin, iron, iron-binding capacity, lipid peroxidation products, and enzymatic and non-enzymatic antioxidants were quantified in serum and in malignant liver tissues and compared with those of normal samples (n = 20). A significant positive correlation between the serum non-ceruloplasmin copper and lipid peroxidation products and negative correlation with antioxidants were observed in hepatocellular carcinoma patients. In liver tissue, glutathione peroxidase, superoxide dismutase, and catalase activity were significantly decreased with concomitant elevation in oxidative stress markers. Our experiment revealed that the elevation in non-ceruloplasmin copper has high relevance with the oxidative stress than the bound copper.
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Affiliation(s)
- Arumugam Geetha
- Department of Biochemistry, Bharathi Women's College, Chennai, 600 108, Tamil Nadu, India.
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Hempel N, Ye H, Abessi B, Mian B, Melendez JA. Altered redox status accompanies progression to metastatic human bladder cancer. Free Radic Biol Med 2009; 46:42-50. [PMID: 18930813 PMCID: PMC2630461 DOI: 10.1016/j.freeradbiomed.2008.09.020] [Citation(s) in RCA: 76] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2007] [Revised: 09/04/2008] [Accepted: 09/15/2008] [Indexed: 02/04/2023]
Abstract
The role of reactive oxygen species (ROS) in bladder cancer progression remains an unexplored field. Expression levels of enzymes regulating ROS levels are often altered in cancer. A search of publicly available microarray data reveals that expression of mitochondrial manganese superoxide dismutase (Sod2), responsible for the conversion of superoxide (O(2)(-)) to hydrogen peroxide (H(2)O(2)), is consistently increased in high-grade and advanced-stage bladder tumors. We aimed to identify the role of Sod2 expression and ROS in bladder cancer. Using an in vitro human bladder tumor model we monitored the redox state of both nonmetastatic (253J) and highly metastatic (253J B-V) bladder tumor cell lines. 253J B-V cells displayed significantly higher Sod2 protein and activity levels compared to their parental 253J cell line. The increase in Sod2 expression was accompanied by a significant decrease in catalase activity, resulting in a net increase in H(2)O(2) production in the 253J B-V cell line. Expression of the prometastatic and proangiogenic factors matrix metalloproteinase 9 (MMP-9) and vascular endothelial-derived growth factor (VEGF), respectively, was upregulated in the metastatic line. Expression of both MMP-9 and VEGF was shown to be H(2)O(2)-dependent, as removal of H(2)O(2) by overexpression of catalase attenuated their expression. Similarly, expression of catalase effectively reduced the clonogenic activity of 253J B-V cells. These findings indicate that metastatic bladder cancer cells display an altered antioxidant expression profile, resulting in a net increase in ROS production, which leads to the induction of redox-sensitive protumorigenic and prometastatic genes such as VEGF and MMP-9.
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Affiliation(s)
- Nadine Hempel
- Center for Immunology and Microbial Disease, Albany Medical College, NY 12208, USA
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Wang SH, Wang YZ, Zhang KY, Shen JH, Zhou HQ, Qiu XY. Effect of superoxide dismutase and malondialdehyde metabolic changes on carcinogenesis of gastric carcinoma. World J Gastroenterol 2005; 11:4305-10. [PMID: 16038025 PMCID: PMC4434653 DOI: 10.3748/wjg.v11.i28.4305] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the relationship between the superoxide dismutase (SOD), malondialdehyde (MDA) metabolic changes and the gastric carcinogenesis.
METHODS: The SOD activity and MDA content were measured in the gastric tissues from the focus center, peripheral and far-end areas of gastric carcinoma (n = 52) and gastric ulcer (n = 10). All the tissues were subjected to routine histological examinations and classifications.
RESULTS: The SOD activity was greatly reduced but the MDA content was markedly increased in the center areas of the non-mucous gastric carcinoma (non-MGC); and the poorly differentiated gastric carcinoma varied. The SOD activity was gradually decreased and the MDA content was gradually increased in the tissues from the focus far-end, peripheral to center areas of non-MGC. Both of the SOD activity and the MDA content were significantly declined and were respectively at same low level in the tissues from the focus center, peripheral, and far-end area with the mucous gastric carcinoma (MGC). In contrast to the gastric ulcer and grade I or II of non-MGC, the same level of the SOD activity and the MDA content were found in the focus center areas. Between non-MGC (groups A-D) and gastric ulcer (group F), the differences of SOD activity and MDA content were very noticeable in the gastric tissues from the focus peripheral and far-end areas, in which the SOD activity showed noticeable increase and the MDA content showed noticeable decrease in the gastric ulcer.
CONCLUSION: The active free radical reaction in the gastric tissues can induce the carcinogenesis of non-MGC. The utmost low ability of antioxidation in the gastric tissues can induce the carcinogenesis of MGC. The metabolic change of the free radicals centralized mostly in the center of ulcerated lesions only, which suggested the ability of antioxidation was declined only in these lesions. However, the metabolism of free radicals varied significantly and the ability of antioxidation declined not only in the local focus area but also in the abroad gastric tissues with gastric carcinoma.
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Affiliation(s)
- Shao-Hong Wang
- Department of Pathology, Central Hospital of Shantou City, Shantou 515031, Guangdong Province, China.
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Martin RCG, Lan Q, Hughes K, Doll MA, Martini BD, Lissowska J, Zatonski W, Rothman N, Hein DW. No apparent association between genetic polymorphisms (-102 C>T) and (-9 T>C) in the human manganese superoxide dismutase gene and gastric cancer(1). J Surg Res 2005; 124:92-7. [PMID: 15734485 DOI: 10.1016/j.jss.2004.09.009] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2004] [Indexed: 01/03/2023]
Abstract
BACKGROUND Manganese superoxide dismutase (MnSOD) plays a critical role in the detoxification of mitochondrial reactive oxygen species, constituting a major cellular defense mechanism against agents that induce oxidative stress. A genetic polymorphism in the mitochondrial targeting sequence of this gene has been associated with increased cancer risk. This one base pair transition (-9 T>C) leads to a Val to Ala amino acid change in the mitochondrial targeting sequence. In addition, the MnSOD promoter contains an activator protein-2 (AP-2) binding site that modifies transcription of MnSOD. Mutations have been identified in the proximal region of the promoter in human tumor cell lines. One of these mutations (-102 C>T) has been shown to change the binding pattern of AP-2, leading to a reduction in transcriptional activity. The aim of our study was to investigate possible associations of the (-9 T>C) and (-102 C>T) polymorphisms with gastric cancer in a population-based case-control study conducted in Warsaw, Poland. MATERIALS AND METHODS DNA was obtained from a population based case-control study of stomach cancer conducted in Warsaw, Poland, between 1994 and 1996. The MnSOD -9 T>C genotype was determined by PCR-RFLP assay. The MnSOD -102 C>T genotype was determined using a TaqMan allele discrimination assay. RESULTS The frequency of the -102 C>T polymorphism was 41% (38/91) in gastric cancer cases and 38% (50/130) in the controls (odds ratio [OR] 1.1, 95% confidence interval [CI] 0.6-2.1). The frequency of the -9 T>C polymorphism was 44% (202/464) in cases and 56% (262/464) in controls (OR 1.1; 95% CI 0.9-1.37). The lack of association was observed in both non-smokers (OR 1.5; 95% CI 0.7-2.34) and smokers (OR 1.1; 95% CI 0.7-1.7). Furthermore, the association was not significant when smokers were segregated by extent of smoking history. CONCLUSION The association of the manganese superoxide dismutase polymorphisms at -102 C>T and the -9 T>C were not found to be associated with gastric cancer in a Polish case-control study.
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Affiliation(s)
- Robert C G Martin
- Department of Surgery, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA.
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