Accelerated glycoxidation takes part in the development of diabetic complications. We determined advanced glycation end-products (AGEs) and advanced oxidation protein products (AOPP) in the sera of 52 patients with diabetes mellitus (DM) - 18 with DM Type 1 and 34 with DM Type 2 and examined their relationship to the compensation of the disease. AGEs were estimated spectrofluorimetrically (350 nm/440 nm) whereas AOPP were determined spectro-photometrically (340 nm). AGEs were elevated only in DM Type 2 (DM2 5.11±1.15x103 AU/g vs controls 4.08±0.71x103 AU/g, p<0.001, vs DM1 4.14±0.86x103 AU/g, p<0.005, DM1 vs controls were not significant). AOPP were elevated significantly in both types of DM with higher levels in DM Type 2 (DM2 157.50±75.15 mmol/l vs healthy subjects 79.80±23.72 mmol/l, p<0.001, vs DM1 97.50±30.91 mmol/l, p<0.005, DM1 vs controls p<0.05). There was a tight correlation between AGEs and AOPP in both types of DM (DM1 r=0.75, DM2 r=0.47 (p<0.05)) and both AGEs and AOPP correlated with triglycerides. In DM Type 1 only, AGEs correlated with HbA1c r=0.47 (p<0.05) and with blood glucose. Slight but not significant differences in AGEs and AOPP levels were observed in patients with or without diabetic complications. Oxidative stress is increased in both types of DM, more in Type 2 where it contributes to the formation of glycoxidation products.
Biomarkers currently play an important role in the detection and management of patients with several different types of gastrointestinal cancer, especially colorectal, gastric, gastro‐oesophageal junction (GOJ) adenocarcinomas and gastrointestinal stromal tumors (GISTs). The aim of this article is to provide updated and evidence‐based guidelines for the use of biomarkers in the different gastrointestinal malignancies. Recommended biomarkers for colorectal cancer include an immunochemical‐based fecal occult blood test in screening asymptomatic subjects ≥50 years of age for neoplasia, serial CEA levels in postoperative surveillance of stage II and III patients who may be candidates for surgical resection or systemic therapy in the event of distant metastasis occurring, K‐RAS mutation status for identifying patients with advanced disease likely to benefit from anti‐EGFR therapeutic antibodies and microsatellite instability testing as a first‐line screen for subjects with Lynch syndrome. In advanced gastric or GOJ cancers, measurement of HER2 is recommended in selecting patients for treatment with trastuzumab. For patients with suspected GIST, determination of KIT protein should be used as a diagnostic aid, while KIT mutational analysis may be used for treatment planning in patients with diagnosed GISTs.
1 November 2005 in Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Receptor for advanced glycation end products (RAGE) may be involved in the pathogenesis of the cancer progression and metastasis. Pathological effects mediated via RAGE are physiologically inhibited by soluble RAGE (sRAGE), so the higher sRAGE levels may confer the patients with cancer with better outcome. The aim was to study sRAGE and RAGE gene polymorphisms in patients with breast cancer. The authors studied sRAGE and RAGE polymorphisms in 120 patients with breast cancer (subdivided based on the clinical stage, histologic grading, expression of hormonal and Her2/neu receptors) and in 92 healthy controls. Despite higher serum concentrations of AGEs, serum concentrations of sRAGE were lower in patients with breast cancer compared to healthy controls (1581 ± 777 versus 1803 ± 632 ng/mL, p < 0.05). Serum levels of sRAGE were higher in patients with advanced breast cancer (stage III), lower grade and positive estrogen receptors, and intermediate positivity of Her2/neu receptors and were also influenced genetically (Gly82Ser and 2184 AG polymorphisms of the RAGE gene). Decreased sRAGE levels in patients with breast cancer may contribute to the progression of the disease. Patients with better outcome (low grade and positive estrogen receptors) have higher sRAGE levels. Progression of the disease, may, however, increase sRAGE levels, possibly as a compensatory mechanism to counteract further progression.