Individual and Combined Effects of CTLA4-CD28 Variants and Oxidant-Antioxidant Status on the Development of Colorectal Cancer.
By: Ozlem Kucukhuseyin, Saime Turan, Karolin Yanar, Soykan Arikan, Yigit Duzkoylu, Seval Aydin, Ufuk Cakatay, Brunilda Mezani, Ammad Ahmad Farooqi, Gulbu Aydinoğlu Isitmangil, Bayram Kiran, Canan Cacina, Ezgi Nurdan Yenilmez, Arzu Ergen, Umit Zeybek, Ilhan Yaylim

Department of Molecular Medicine, Institute of Experimental Medicine, Capa Medical Faculty, Istanbul University, Istanbul, Turkey ozlem.kh@gmail.com ilhanyaylim@gmail.com.
2015-9-27; doi:
Abstract

Background

Colorectal cancer (CRC) is the third most frequent cancer worldwide. Research has revealed the contributions of the immune system and anti-inflammatory pathways in the development of cancer. The balance between cluster of differentiation 28 (CD28) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) signaling is important for the regulation of immune responses. The oxidant-antioxidant balance by sustaining redox control via several defense mechanisms is also an important factor for the progression of cancer. The aim of the present study was to determine the distribution of CTLA4/CD28 variants and oxidant-antioxidant status in patients with CRC.

Materials

This study enrolled 80 patients with CRC and 115 healthy controls. We used a spectrophotometric assay to detect the levels of lipid peroxidation products malon dialdehyde (MDA) and lipid hydroperoxide (LHP), and measured the concentration of protein damage products, advanced oxidation protein products (AOPP) and protein carbonyl (PCO). Additionally, antioxidant levels were detected by measuring copper, zinc, superoxide dismutase (Zn-Cu SOD) and total thiol (T-SH) levels, and advanced glycation end-products (AGEs). The CTLA4 -318C>T, CTLA4 49A>G and CD28C>T genotypes were determined by using restriction enzymes.

Results

AOPP and PCO levels were increased in patients with CRC as well as those of LHP, MDA and AGE, while the levels of antioxidants such as Cu-Zn SOD and T-SH were lower. Lower serum levels of CTLA4 and higher serum levels of CD28 were detected in patients and, an association of the CTLA4 -318C/T polymorphism was found in patients with CRC.

Conclusion

Our oxidative stress was increased in patients with CRC, suggesting the contribution of this disturbed oxidative status to serum CTLA4 and CD28 levels, and to the pathogenesis of CRC.



Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

PMID:26408701






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