The effect of adjuvant chemotherapy on plasma TAT and F 1+2 levels in patients with breast cancer.

INTRODUCTION: Increased thromboembolic disorders and chemotherapy-induced thromboembolic events are well known phenomena in patients with breast cancer. Antithrombin III (AT III) inactivates thrombin, resulting in increased thrombin-antithrombin (TAT) levels. Activated factor X cleaves prothrombin and thrombin, resulting in increased levels of prothrombin fragment 1+2 (F 1+2). Increased TAT and F 1+2 levels show coagulation activation. The aim of this study was to examine plasma levels of TAT and F 1+2 and the effect of anthracycline-based chemotherapy on plasma TAT and F 1+2 in patients with operable breast cancer. MATERIALS AND METHODS: Seventy patients and 30 age-matched healthy controls were enrolled. Levels of TAT and F 1+2 were investigated before and after adjuvant chemotherapy. Basal levels (pre-chemotherapy) of TAT and F 1+2 in patients were compared with those in healthy controls and patient levels after 3 cycles of chemotherapy. Levels of TAT and F 1+2 were determined using the ELISA method. RESULTS: TAT and d-dimer levels were significantly higher in patients, (P: 0.02 and P<0.001, respectively). Post-chemotherapy F 1+2 levels were higher than basal levels (P: 0.02). F 1+2 levels were higher in patients, although the difference was not statistically significant (P: 0.52). There was no difference between basal and post-chemotherapy TAT levels. DISCUSSION: In conclusion, while higher post-chemotherapy F 1+2 levels suggest that the cumulative effect of chemotherapy increases the risk of thrombosis, TAT and d-dimer levels indicate that the effect of the cancer further increases the risk of thrombosis in patients with operable breast cancer.

Investigation of tyrphostin AG 556 for testicular torsion-induced ischemia reperfusion injury in rat.

OBJECTIVE: To investigate the effects of tyrphostin AG 556, a tyrosine kinase inhibitor (TKI) in an experimental model of testicular ischemia-reperfusion (I/R) injury. MATERIAL AND METHODS: Twenty-four adult male rats were randomly divided into four groups (n = 6): sham, torsion/detorsion (T/D), T/D + dimethylsulfoxide (DMSO) (vehicle group), and T/D + DMSO + tyrphostin AG 556. Testicular torsion was achieved by rotating the left testis 720° clockwise for 4 h. Thirty minutes before detorsion, 3 mg/kg tyrphostin AG 556 was injected transperitoneally in the AG 556 group and DMSO was injected transperitoneally in the DMSO group. After 2 h of reperfusion arterial blood samples were collected for biochemical analysis for malondialdehyde (MDA), ischemia modified albumin (IMA), SCUBE1 (signal peptide-CUB [complement C1r/C1s, Uegf, and Bmp1] and EGF [epidermal growth factor] like domain-containing protein 1), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) parameters, and ipsilateral orchiectomies were performed for histopathological examination based on the semi-quantitative Johnsen's mean testicular biopsy score (MTBS) in all groups. RESULTS: Tyrphostin AG 556 exhibited a protective effect against I/R injury in testicular torsion. Of the biochemical parameters evaluated as a result of testicular I/R, IMA, MDA, and TOS levels were significantly elevated. There was no significant difference in terms of these biochemical parameters between the sham and AG 556 groups. Significant histopathological injury was determined by comparing the T/D and sham groups. According to histopathological injury scores, significant differences were determined between T/D and AG 556 groups and between AG 556 and sham groups. AG 556 had a superior improving effect on Johnsen's scores than DMSO. CONCLUSIONS: Our results suggest that the use of tyrphostin AG 556 prior to testicular reperfusion has a protective effect against testicular I/R injury.