Enzimas que hidrolisam nucleotídeos da adenina em plaquetas de pacientes com câncer de mama

Abstract

The activities of the enzymes NTPDase (E.C. 3.6.1.5, apyrase, ecto/CD39) and 5'-nucleotidase (E.C. 3.1.3.5, CD73) were analyzed in platelets from breast cancer patients. Initially, patients were compared in terms of time (years) of use of tamoxifen. The following groups were studied: breast cancer patients who did not use tamoxifen, patients using tamoxifen for 1-48 months, patients using tamoxifen for 49-84 months, and controls (healthy subjects). Results demonstrated that ATP hydrolysis was enhanced (F(3,114)=8.53; p< 0.001) and ADP hydrolysis was reduced (F(3,106)=5.09, p=0.002) as a function of tamoxifen use, while AMP hydrolysis was unchanged. Next, patients were compared statistically according to disease staging, determined by the TNM staging system for classifying breast tumor. ATP hydrolysis was significantly elevated in patients with stage I and II breast cancer (F(4,113)=4.35; p= 0.003), but was normal in patients with stage III and IV cancer. ADP hydrolysis was reduced in stages II to IV (F(4,105)=3.88, p=0.006) and AMP hydrolysis was elevated in stage II (F(4,105)=3.45 p= 0.01), but was normal in stages III and IV. Platelet aggregation time was similar in all patients regardless of tamoxifen use or disease stage. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were also within the normal range and similar among groups in all situations. Similarly, fibrinogen and fibrin degradation product (FDP) were unchanged in all groups. In conclusion, our study demonstrated for the first time that hydrolysis of adenine nucleotides is modified in platelets from breast cancer patients taking tamoxifen.