Individual and Combined Effects of CTLA4-CD28 Variants and Oxidant-Antioxidant Status on the Development of Colorectal Cancer

Kucukhuseyin O., Turan S., Yanar K., Arıkan S., DUZKOYLU Y., Aydin S., ...Daha Fazla

ANTICANCER RESEARCH, cilt.35, sa.10, ss.5391-5400, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 35 Sayı: 10
  • Basım Tarihi: 2015
  • Dergi Adı: ANTICANCER RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.5391-5400
  • Anahtar Kelimeler: CTLA4, CD28, polymorphism, lipid hydroperoxide (LHP) malon dialdehyde (MDA), advanced oxidation protein products (AOPP), protein carbonyl (PCO), superoxide dismutase, advanced glycation end-products (AGEs), copper, zinc, T-LYMPHOCYTE ANTIGEN-4, OXIDATIVE STRESS, CTLA-4 BLOCKADE, LIPID-PEROXIDATION, GENETIC-VARIATIONS, IMMUNE-RESPONSE, REGULATORY T, CUTTING EDGE, BREAST, CELLS
  • İstanbul Üniversitesi Adresli: Evet

Özet

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 and Methods: 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.