Early Detection of High Oxidative Activity in Patients With Adenomatous Intestinal Polyps and Colorectal Adenocarcinoma: Myeloperoxidase and Oxidized Low-Density Lipoprotein in Serum as New Markers of Oxidative Stress in Colorectal Cancer

Crespo‐Sanjuán, Jesús; Calvo-Nieves, María Dolores; Aguirre-Gervás, Beatriz; Herreros-Rodríguez, José; Velayos-Jiménez, Benito; Alija, María José Castro; Muñoz-Moreno, María Fe; Sánchez, Diego; Zamora-González, Nuria; Bajo‐Grañeras, Raquel; García-Centeno, Rosa M.; Cabrerizo, María E. Largo; Bustamante, María R.; Garrote, José Antonio

doi:10.1309/lmzjju6bc86wudhw

Cited by 29 publications

(23 citation statements)

References 24 publications

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“…Beta carotene, a pro-vitamin A carotenoid deficiency not only favors polyp dysplasia leading to CRC development but also associated with poor absorption of vitamin E, resulting in its deficiency leading to oxidative insult causing upregulated intracellular signaling which mediates tumor growth (23, 24). Vitamin C plays a key role in the production of collagen and its deficit upsets the integrity of intracellular matrix and promotes tumor proliferation.…”

Section: Discussionmentioning

confidence: 99%

Implications of Isoprostanes and Matrix Metalloproteinase-7 Having Potential Role in the Development of Colorectal Cancer in Males

Rasool

Malik

Ghuman³

et al. 2018

Front. Oncol.

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BackgroundColorectal cancer (CRC) is the third most common type of cancer and leading cause of death worldwide. Major risk factors involved in the development of CRC are increased dietary sources, genetics, and increasing age. Purpose of the study was to find the role of different variables in the progression of CRC.Methodology50 blood samples from CRC patients and 20 samples from control were collected. Serum was separated from the blood by centrifugation. This serum was assessed for several antioxidants like superoxide dismutase (SOD), glutathione, glutathione peroxidase, glutathione reductase, catalase, vitamin A, C, and E, and pro-oxidants such as malondialdehyde, advanced oxidation protein products (AOPPs), and AGEs according to their respective protocols. Matrix metalloproteinase-7 (MMP-7) and isoprostanes were assessed by ELISA kits.ResultsLower levels of GSH (4.86 ± 0.78 vs 9.65 ± 1.13 μg/dl), SOD (0.08 ± 0.012 vs 0.46 ± 0.017 μg/dl), CAT (2.45 ± 0.03 vs 4.22 ± 0.19 μmol/mol of protein), and GRx (5.16 ± 0.06 vs 7.23 ± 0.36 μmol/ml) in the diseased group were recorded as compared with control. Higher levels of GPx (6.64 ± 0.19 mmol/dl) were observed in the subjects in comparison with control group (1.58 ± 0.30 mmol/dl). Highly significant decreased levels of vitamin A (0.81 ± 0.07 vs 2.37 ± 0.15 mg/ml), vitamin E (15.42 ± 1.26 vs 25.96 ± 2.19 mg/ml), and vitamin C (47.67 ± 7.69 vs 80.37 ± 10.21 mg/ml) were observed in the patients in contrast to control group. The reversal of antioxidants in later stages of CRC may be due to compensatory mechanisms in cancerous cells. The levels of MDA (nmol/ml) were also assessed, which shows significantly increased level in CRC patients as compared with control groups (3.67 ± 0.19 vs 1.31 ± 0.27). The levels of protein oxidation products [AGEs (2.74 ± 0.16 vs 0.84 ± 0.05 IU) and AOPPs (1.32 ± 0.02 vs 0.82 ± 0.07 ng/ml)] were significantly increased in subjects as compared with control. The levels of MMP-7 (64.75 ± 3.03 vs 50.61 ± 4.09 ng/ml) and isoprostanes (0.71 ± 0.03 vs 0.16 ± 0.02 ng/ml) were also analyzed. This shows that the levels of isoprostanes increased due to high lipid peroxidation mediate higher levels of MMP-7, which promotes development of CRC.ConclusionFollowing study suggested that elevated oxidative and inflammatory status along with lipid peroxidation and matrix metalloproteinases are the chief contributors in the progression of CRC.

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Section: Discussionmentioning

confidence: 99%

Implications of Isoprostanes and Matrix Metalloproteinase-7 Having Potential Role in the Development of Colorectal Cancer in Males

Rasool

Malik

Ghuman³

et al. 2018

Front. Oncol.

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“…All the changes can be caused by oxidative stress, such as cancer suppressor [23], cell normal functions [24], special responses for pathogens [25], maximal actions, and antigen presentation [26] (Figure 6). Pathway analysis revealed that, in intestinal mucosa tissues of participants from high altitude, many pathway genes had aberrant expression and may be also related with oxidative stress, especially in inflammatory bowel diseases [27, 28], myeloperoxidase [29], ROS production [10], apoptotic cell death [30], tissue damage [31], interleukin-1 [32], oxidative modification [33], cystic fibrosis [34], natural killer cells activity [35], lymphocytes [36], fibrinolysis [37] and so on (Figure 7). …”

Section: Resultsmentioning

confidence: 99%

Genome‐Wide Transcriptional Analysis Reveals the Protection against Hypoxia‐Induced Oxidative Injury in the Intestine of Tibetans via the Inhibition of GRB2/EGFR/PTPN11 Pathways

Gesang

Zhang

et al. 2016

Oxidative Medicine and Cellular Longevity

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The molecular mechanisms for hypoxic environment causing the injury of intestinal mucosal barrier (IMB) are widely unknown. To address the issue, Han Chinese from 100 m altitude and Tibetans from high altitude (more than 3650 m) were recruited. Histological and transcriptome analyses were performed. The results showed intestinal villi were reduced and appeared irregular, and glandular epithelium was destroyed in the IMB of Tibetans when compared with Han Chinese. Transcriptome analysis revealed 2573 genes with altered expression. The levels of 1137 genes increased and 1436 genes decreased in Tibetans when compared with Han Chinese. Gene ontology (GO) analysis indicated most immunological responses were reduced in the IMB of Tibetans when compared with Han Chinese. Gene microarray showed that there were 25-, 22-, and 18-fold downregulation for growth factor receptor-bound protein 2 (GRB2), epidermal growth factor receptor (EGFR), and tyrosine-protein phosphatase nonreceptor type 11 (PTPN11) in the IMB of Tibetans when compared with Han Chinese. The downregulation of EGFR, GRB2, and PTPN11 will reduce the production of reactive oxygen species and protect against oxidative stress-induced injury for intestine. Thus, the transcriptome analysis showed the protecting functions of IMB patients against hypoxia-induced oxidative injury in the intestine of Tibetans via affecting GRB2/EGFR/PTPN11 pathways.

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“…Since prototypical swarming bacteria (e.g., Proteus mirabilis, Pseudomonas aeruginosa) are associated with virulence (7,14), we surmised that bacterial swarming might be 65 well represented in colonoscopy samples and feces from humans with bacterial virulence associated pathologies (e.g., intestinal inflammation) (15). Colonoscopy aspirates were obtained from individuals with an active illness (inflammatory bowel disease -Crohn's and ulcerative colitis and other common forms of intestinal stress like intestinal polyps (16,17) as well as age and gender matched controls (those without a clinically active illness). Within our sampling pool, bacterial 70 collective spreading on soft agar was over-represented in cases with overt or clinically active intestinal stress ( Fig.…”

Section: Main Textmentioning

confidence: 99%

Bacterial Swarmers exhibit a Protective Response to Intestinal Stress

Chen

et al. 2019

Preprint

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Bacterial swarming is a conserved and distinct form of bacterial motility that allows for 29 rapid migration over a surface. Swarming motility is often oppositely regulated and 30 antagonistic to biofilm formation 1 . To-date, while bacterial biofilms have been associated 31 with pathogenesis and pathobiology of human diseases (e.g., infections, inflammation and 32 cancer) 2-4 , there are very few examples of swarming behaviors that uniquely define or align 33 with human pathophysiology (e.g., antibiotic resistance) 5,6,7 . Here we report that bacterial 34 swarming is highly predictive of the presence of intestinal stress in mice, pigs and humans. 35 Using a modified agar plate assay, we isolated from murine feces a novel Enterobacter 36 hyperswarming strain, SM3 that demonstrated significant protection from intestinal 37 inflammation and promoted restitution in a mouse model of colitis. As opposed to bacterial 38 biofilms 8 , we report that the swarming phenotype protects against intestinal inflammation 39 in mice. Mechanistically, commensal swarming strains rapidly consume oxygen in vitro and 40 in vivo, leading to a favorable anaerobic environment conducive to the growth of beneficial 41 anaerobes. The swarming property of bacteria rather than the individual strains 42 themselves, independently lends the ability to protect and heal from intestinal 43 inflammation. This work identifies a new paradigm in which intestinal stress, specifically 44 inflammation, allows for emergence of swarming bacteria, which in turn act to suppress 45 inflammation via mechanisms that are associated in part with oxygen depletion and bloom 46 of beneficial anaerobes. 47

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Early Detection of High Oxidative Activity in Patients With Adenomatous Intestinal Polyps and Colorectal Adenocarcinoma: Myeloperoxidase and Oxidized Low-Density Lipoprotein in Serum as New Markers of Oxidative Stress in Colorectal Cancer

Abstract: The oxidation process, which can cause mutations leading to CRC, begins development in the polyp stage. This process may be detected early by monitoring serum markers such as MPO and oxLDL.

Cited by 29 publications

References 24 publications

Implications of Isoprostanes and Matrix Metalloproteinase-7 Having Potential Role in the Development of Colorectal Cancer in Males

Implications of Isoprostanes and Matrix Metalloproteinase-7 Having Potential Role in the Development of Colorectal Cancer in Males

Genome‐Wide Transcriptional Analysis Reveals the Protection against Hypoxia‐Induced Oxidative Injury in the Intestine of Tibetans via the Inhibition of GRB2/EGFR/PTPN11 Pathways

Bacterial Swarmers exhibit a Protective Response to Intestinal Stress

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