Serum sICAM, sVCAM and sE-selectin levels in colorectal cancer patients.

Colorectal cancer (CRC) is one of the most common cancers of the gastrointestinal tract and the fourth cause of cancers death in the world. Soluble adhesion molecules (CAMs) are thought to have an important role in host defense against carcinogenesis. They are biomarkers of inflammation and indicators of the immune response to tumors. The study included 40 CRC patients without remote metastases and 24 control subjects. Serum concentrations of sE-selectin, sICAM and sVCAM in patients with CRC were investigated by ELISA method. The level of the sCAMs decreased significantly after radical tumor resection. Preoperative serum concentrations of sICAM and sVCAM in CRC patients were significantly higher compared to the control group, whereas there were no differences regarding serum sE-selectin. Serum levels of sE-selectin, sICAM and sVCAM correlated significantly with each other. There was a significant correlation of serum levels of sICAM-1 and sVCAM-1, but not sE-selectin, with TNM stage and lymph node involvement. No significant relationship was found between serum concentrations of sICAM-1, sVCAM-1 and sE-selectin in CRC patients and patients' age or gender. Our findings suggest that an improved understanding of the mechanisms of membrane shedding of sICAM, sVCAM and sE-selectin is required to delineate their role in tumor progression

Exploring Post-translational Arginine Modification Using Chemically Synthesized Methylglyoxal Hydroimidazolones

The methylglyoxal-derived hydroimidazolones (MG-Hs, Figure 1A) comprise the most prevalent class of non-enzymatic, post-translational modifications of protein arginine residues found in nature. These adducts form spontaneously in the human body, and are also present at high levels in the human diet. Despite numerous lines of evidence suggesting that MG-H–arginine adducts play critical roles in both healthy and disease physiology in humans, detailed studies of these molecules have been hindered by a lack of general synthetic strategies for their preparation in chemically homogeneous form, and on scales sufficient to enable detailed biochemical and cellular investigations. To address this limitation, we have developed efficient, multi-gram-scale syntheses of all MG-H–amino acid monomers in 2–3 steps starting from inexpensive, readily available starting materials. Thus, MG-H derivatives were readily incorporated into oligopeptides site-specifically using standard solid-phase peptide synthesis (SPPS). Access to synthetic MG-H-peptide adducts has enabled detailed biochemical investigations, which have revealed a series of novel and unexpected findings. First, one of the three MG-H isomers – MG-H3 – was found to possess potent, pH-dependent antioxidant properties in biochemical and cellular assays intended to replicate redox processes that occur in vivo. Computational and mechanistic studies suggest that MG-H3-containing constructs are capable of participating in mechanistically distinct H-atom-transfer and single-electron-transfer oxidation processes. Notably, the product of MG-H3 oxidation was unexpectedly observed to disassemble into the fully unmodified arginine residue and pyruvate in aqueous solution. We believe these observations to reflect meaningfully on the role(s) of MG-H–protein adducts in human physiology, and expect the synthetic reagents reported herein to enable investigations into non-enzymatic protein regulation at an unprecedented level of detail