title: Nitric oxide synthesis modulation - a possible diagnostic and therapeutic target in colorectal cancer.
abstract: OBJECTIVE
  Considering the contradictory literature data about the role of nitric oxide (NO) in colon carcinogenesis, the purpose of this study was to examine the changes of L-arginine metabolites in colon cancer and surrounding tissue as possible molecular markers of tumor behavior after surgery and the possibility of NO synthesis modulation in new individualized therapeutic strategies.
  
  
  METHODS
  The study encompassed 50 patients who underwent surgery for colorectal cancer (CRC). The three tissue specimens were taken by surgery (tumor, adjacent and healthy tissue) and the concentrations of NO2+NO3, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) were determined in the tissue specimens.
  
  
  RESULTS
  The results proved higher NO2+NO3 concentrations in adjacent tissue compared to the tumor, implicating high angiogenic potential of the tumor-surrounding tissue, which could have clinical importance in the assessment of the probability of tumor local recurrence and metastasis. Increased ADMA concentrations in tumor tissue associated with low NO levels, could lead to new therapeutic strategies directed to the use of inhibitors of NO synthesis as ideal candidates for molecular therapy of CRC. ADMA concentration in adjacent tissue was an independent predictor of distant metastasis.
  
  
  CONCLUSIONS
  The obtained results suggest that determination of the examined biomarkers in CRC and adjacent tissue samples could give useful information about tumor proliferative and angiogenic potential, which in turn could enable individualization of therapy and the choice of proper adjuvant therapy in patients with CRC.
authors.affiliation: Clinic for Surgery, Clinical Centre Nis, Nis, Serbia.
authors.forename: Branko
authors.initials: B
authors.lastname: Brankovic
authors.forename: Goran
authors.initials: G
authors.lastname: Stanojevic
authors.forename: Ivana
authors.initials: I
authors.lastname: Stojanovic
authors.forename: Andrej
authors.initials: A
authors.lastname: Veljkovic
authors.forename: Gordana
authors.initials: G
authors.lastname: Kocic
authors.forename: Predrag
authors.initials: P
authors.lastname: Janosevic
authors.forename: Milica
authors.initials: M
authors.lastname: Nestorovic
authors.forename: Dejan
authors.initials: D
authors.lastname: Petrovic
authors.forename: Boris
authors.initials: B
authors.lastname: Djindjic
authors.forename: Ducica
authors.initials: D
authors.lastname: Pavlovic
authors.forename: Zoran
authors.initials: Z
authors.lastname: Krivokapic
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D009569:Nitric Oxide; C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine