Analysis of Oxidative Stress-Related Markers in Crohn's Disease Patients at Surgery and Correlations with Clinical Findings.
Impact Factor: 5.014
Level of Evidence: IV
Type of Study: Case-control
Sample Size: 71 subjects (54 case, 17 control)
Methods: Cases were patients with Crohn’s disease (CD) relapse requiring surgery. Serum was isolated from blood samples taken before surgery. Demographic and clinical characteristics were also determined. AGEs were determined by fluorescence intensity.
Statistics: Kolmogorov-Smirnov test for normality, Student’s t-test, Mann-Whitney test, chi-square or Fisher exact test, step-wide multiple linear regression
Results: AGEs were significantly increased in patients with CD vs. controls (p<0.001). The overall oxidative score, which included AGE and other parameters for potential oxidative damage was also significantly increased in cases. Antioxidant status in CD patients with high oxidative stress was not disproportionate, however.
Discussion/Conclusion: Increased AGE levels are seen in patients with CD. The mechanism of oxidative stress is not only due to imbalanced oxidative products vs. antioxidants, but oxidative products like AGEs could enhance inflammatory pathways.
Luceri C, Bigagli E, Agostiniani S, et al. Analysis of Oxidative Stress-Related Markers in Crohn's Disease Patients at Surgery and Correlations with Clinical Findings. Antioxidants (Basel). 2019;8(9):378. Published 2019 Sep 6. doi:10.3390/antiox8090378
The Association between Glyceraldehyde-Derived Advanced Glycation End-Products and Colorectal Cancer Risk.
Impact factor: 5.057
Level of Evidence: III
Study: Case Control
Sample Size: 1,055 European subjects
Intro: Glycer-AGE has been identified as perhaps the most toxic end-product from the AGE family. In this prospective study, circulating glycer-AGE levels were measured from serum samples of colorectal cancer patients and were compared to serum levels of a control group; it was hypothesized that colorectal cancer patients would show a positive association with serum glycer-AGE levels due to a poor diet, leading to energy excess and obesity, which is commonly observed in these patients.
Methods: glycer-AGEs were measured by ELISA
Stats: Sub-group analyses showed possible divergence between colon cancer and rectal cancer (odds ratio for colon cancer = 0.83; 95% CI, 0.57-1.22; odds ratio for rectal cancer = 1.90; 95% CI, 1.14-3.19; heterogeneity = 0.14)
Conclusion: Circulating glycer-AGEs were not associated with the overall risk of colon cancer but showed a positive association with the risk of rectal cancer in a sub-group analysis, particularly when the patient consumed alcohol. A few limitations of this study include only a one-time glycer-AGE measurement was taken at the time of recruitment and the sub-group analysis had a much lower sample size than the overall group.
Kong SY, Takeuchi M, Hyogo H, McKeown-Eyssen G, Yamagishi S, Chayama K, O'Brien PJ, Ferrari P, Overvad K, Olsen A, Tjønneland A, Boutron-Ruault MC, Bastide N, Carbonnel F, Kühn T, Kaaks R, Boeing H, Aleksandrova K, Trichopoulou A, Lagiou P, Vasilopoulou E, Masala G, Pala V, Santucci De Magistris M, Tumino R, Naccarati A, Bueno-de-Mesquita HB, Peeters PH, Weiderpass E, Quirós JR, Jakszyn P, Sánchez MJ, Dorronsoro M, Gavrila D, Ardanaz E, Rutegård M, Nyström H, Wareham NJ, Khaw KT, Bradbury KE, Romieu I, Freisling H, Stavropoulou F, Gunter MJ, Cross AJ, Riboli E, Jenab M, Bruce WR. The Association between Glyceraldehyde-Derived Advanced Glycation End-Products and Colorectal Cancer Risk. Cancer Epidemiol Biomarkers Prev. 2015 Dec;24(12):1855-63. doi: 10.1158/1055-9965.EPI-15-0422. Epub 2015 Sep 24. PMID: 26404963; PMCID: PMC6284787.
Clinical significance of AGE-RAGE axis in colorectal cancer: associations with glyoxalase-I, adiponectin receptor expression and prognosis
Summary: AGEs are an important contributor to the pathogenesis of colorectal carcinoma. CRC is the 3rd most common malignancy in men and second in women. It is now evident that high calorie Western diets rich in fat play an important row in the pathogenesis of colorectal carcinoma. As it is currently evident that AGE levels are increased by hyperglycemia, ingestion of foods rich with AGEs are being investigated as being contributive for CRC development. Two enzymes, glyoxalase-I (GLO-I) and glyoxylase-II (GLO-II) are important mediators in protecting proteins, nucleotides, and phospholipids from AGE-associated damage by decreasing the levels of AGE precursors. Tumor cells with high glycolytic rate benefit most from the glyoxalase detoxification system to reduce the toxic burden of these precursors. Elevated levels of GLO-I and GLO-II gene expression have been identified in breast, lung, bladder, gastric cancers among others. However, increased levels of GLO-I have rarely been reported in colorectal carcinoma. Earlier studies have demonstrated a 2-fold increased activity in tumor versus normal colonic epithelium. Another class of proteins, Adiponectin, a peptide hormone produced exclusively by fat tissue and is implicated in glucose metabolism, appears to reduce insulin resistance. Receptors for this hormone, AdipoR1 and AdipoR2 are known to be increased in colorectal cancer tumors. Epidemiologic studies portray an inverse association between this hormone’s levels and colorectal cancers. Furthermore, adiponectin was found to be inversely associated with AGE/RAGE serum ratio and similarly plasma levels of N-carboxymethal lysine (CML), a prominent type of AGE, correlated negatively with adiponectin levels in overweight patients. In-vitro experiments support the link between AGE and adiponectin expression, implicating the anti-oxidative property of the latter and arguing in favor of its protective effects on AGEs-induced endothelial dysfunction. Current data on GLO-I, AdipoR1 and AdipoR2 in relation to the AGE-RAGE axis in CRC is insufficient.
This is a retrospective study performed on archival tissue specimens from 133 cases of primary colorectal adenocarcinoma diagnosed between 2000 and 2010 in 3 Greek hospitals. Tissues were immunostained for AGE, RAGE, GLO-I, AdipoR1 and AdipoR2. Although there was no difference in the extent of AGE and RAGE immunoexpression between normal and neoplastic areas, intensity of both AGE and RAGE expression was higher in tumoral tissue (p = 0.0001 for both relationships). GLO-I expression was negatively correlated with tumor T-category (p = 0.10). An inverse relation between GLO-I and AGE expression was clearly observed in normal colonic mucosa and colon cancer cell lines, while it was less evident in CRC tissue at both immunohistochemical and WB analysis. WB analysis revealed increased expression of AGE and RAGE. AdipoR1 immunostaining revealed lower levels in CRC than in normal colonic epithelium while no significant difference was observed regarding the percentage of positive cells in neoplastic vs. non-neoplastic epithelium. AdipoR2 expression levels are positively associated with tumor grade. Survival analysis failed to reveal AGE or RAGE as prognostic factors for development of CRC. After stage stratification, GLO-I overexpression was prognostic for higher grade tumors, suggesting that CRC cells overexpressing GLO-I gain an advantage by aiding in detoxification of AGE byproducts such as methylglyoxal. Patients with high levels of AdipoR2 expression had a significantly shorter survival, suggesting that high expression is associated with advanced disease. In summary, GLO-I and AdipoR2 were found to be relatively prognostic of poor outcomes for CRC patients while AdipoR1 levels are inversely associated with CRC progression, therefore suggesting a protective role in normal tissue.
Sakellariou S, Fragkou P, Levidou G, et al. Clinical significance of AGE-RAGE axis in colorectal cancer: associations with glyoxalase-I, adiponectin receptor expression and prognosis. BMC Cancer. 2016;16:174. Published 2016 Mar 1. doi:10.1186/s12885-016-2213-5