title: Individual and Combined Effects of CTLA4-CD28 Variants and Oxidant-Antioxidant Status on the Development of Colorectal Cancer.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Medicine, Institute of Experimental Medicine, Capa Medical Faculty, Istanbul University, Istanbul, Turkey ozlem.kh@gmail.com ilhanyaylim@gmail.com.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Kucukhuseyin
authors.affiliation: Department of Molecular Medicine, Institute of Experimental Medicine, Capa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Saime
authors.initials: S
authors.lastname: Turan
authors.affiliation: Department of Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Karolin
authors.initials: K
authors.lastname: Yanar
authors.affiliation: Department of Surgery, Istanbul Educating and Training Hospital, Istanbul, Turkey.
authors.forename: Soykan
authors.initials: S
authors.lastname: Arikan
authors.affiliation: Department of Surgery, Istanbul Educating and Training Hospital, Istanbul, Turkey.
authors.forename: Yigit
authors.initials: Y
authors.lastname: Duzkoylu
authors.affiliation: Department of Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Seval
authors.initials: S
authors.lastname: Aydin
authors.affiliation: Department of Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Ufuk
authors.initials: U
authors.lastname: Cakatay
authors.affiliation: Department of Molecular Medicine, Institute of Experimental Medicine, Capa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Brunilda
authors.initials: B
authors.lastname: Mezani
authors.affiliation: Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore, Pakistan.
authors.forename: Ammad Ahmad
authors.initials: AA
authors.lastname: Farooqi
authors.affiliation: Laboratory of Immunology, Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey.
authors.forename: Gulbu Aydinoğlu
authors.initials: GA
authors.lastname: Isitmangil
authors.affiliation: Department of Biology, Medical Faculty of Kastamonu University, Kastamonu, Turkey.
authors.forename: Bayram
authors.initials: B
authors.lastname: Kiran
authors.affiliation: Department of Molecular Medicine, Institute of Experimental Medicine, Capa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Canan
authors.initials: C
authors.lastname: Cacina
authors.affiliation: Department of Molecular Medicine, Institute of Experimental Medicine, Capa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Ezgi Nurdan
authors.initials: EN
authors.lastname: Yenilmez
authors.affiliation: Department of Molecular Medicine, Institute of Experimental Medicine, Capa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Arzu
authors.initials: A
authors.lastname: Ergen
authors.affiliation: Department of Molecular Medicine, Institute of Experimental Medicine, Capa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Umit
authors.initials: U
authors.lastname: Zeybek
authors.affiliation: Department of Molecular Medicine, Institute of Experimental Medicine, Capa Medical Faculty, Istanbul University, Istanbul, Turkey ozlem.kh@gmail.com ilhanyaylim@gmail.com.
authors.forename: Ilhan
authors.initials: I
authors.lastname: Yaylim
mesh_terms: D062107:Advanced Oxidation Protein Products / Q000378:metabolism; D000368:Aged; D018106:CD28 Antigens / Q000097:blood / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide; D050050:Protein Carbonylation; D013053:Spectrophotometry
chemical_list: D062107:Advanced Oxidation Protein Products; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human
keywords: CD28; CTLA4; advanced glycation end-products (AGEs); advanced oxidation protein products (AOPP); copper; lipid hydroperoxide (LHP) malon dialdehyde (MDA); polymorphism; protein carbonyl (PCO); superoxide dismutase; zinc