Role of the purinergic system in patients with cervical intraepithelial neoplasia and uterine cancer.

INTRODUCTION: Cervical cancer remains the second leading cause of death among women. Intraepithelial neoplasias and uterine invasive cancer are frequently associated with disturbances in coagulation and changes in the concentrations of adenine nucleotides. This work intended to analyze changes in extracellular adenine nucleotide hydrolysis and blood platelet aggregation in patients diagnosed for cervical intraepithelial neoplasia in different stages as well as uterine invasive cancer. PATIENTS AND METHODS: NTPDase, E-NPP, 5'-nucleotidase, total ADA and its isoforms (ADA1 and ADA2), as well as the platelet aggregation from patients with different stages of cervical intraepithelial neoplasia (NICs I, NIC II, NIC III) and uterine invasive cancer were verified. RESULTS: Neither ATP hydrolysis nor E-NPP activity was changed by the neoplasia stage. On the other hand, ADP and AMP hydrolysis as well as ADA activity were enhanced in NIC I group. AMP hydrolysis was also increased in the cancer group. ADA 1 was the ADA isoform found in platelets from both control and patient groups. CONCLUSION: Our results showed for the first time that NTPDase, 5'-nucleotidase, E-NPP and ADA are not sensible regarding the grade of neoplasia development, since no significant difference was found between the groups studied. Only ADP hydrolysis and ADA activity showed a significant enhancement in NIC I group related to the other stages possibly as a result of the beginning of the neoplasic transformation. This increase could be reflecting a body's reaction against the probable high adenosine levels. We propose for the first time that the ADA isoform present in platelets is ADA 1.

Nucleotide degrading enzymes in platelets from uterine cervical neoplasia patients treated with conization or radiotherapy.

BACKGROUND: Uterine cervical neoplasia is an important worldwide malignancy sometimes associated with thrombosis. Ectonucleotidases are membrane-bound enzymes which participate in thromboregulation by hydrolyzing adenine nucleotides in the extracellular medium. In this sense, we aimed to investigate their activity in patients with uterine cervical neoplasia. METHODS: We evaluated NTPDase and 5'-nucleotidase activities from patients previously treated for uterine cervical neoplasia with either conization or radiotherapy (RTX). These patients were divided into four groups: two conization groups (I and II) and two RTX groups (III and IV), which were further divided based on the amount of time that had passed since the conclusion of their treatment, where groups I and III were extended-remission-period groups (patients with 1 to 5 years elapsed after the conclusion of treatment), and groups II and IV were recently treated patients (treated up to three months before). RESULTS: For both conization and RTX groups, ATP and ADP hydrolysis decreased in the extended-remission groups when compared to the control and recently treated groups. On the other hand, AMP hydrolysis was decreased in all the treated groups (both conization and RTX) compared to the control. CD39 expression was decreased in extended-remission groups (I and III) when compared to the other groups. CONCLUSIONS: NTPDase protects against platelet aggregation and 5'-nucleotidase is more involved in the control of adenosine formation.

Oxidative status in patients submitted to conization and radiation treatments for uterine cervix neoplasia.

BACKGROUND: Cervical cancer is a major cause of morbidity among women. We investigated the treatment effect on oxidative status from patients submitted to radiotherapy or conization surgery to high-grade SIL (squamous intraepithelial lesion) treatment, and oxidative profile from patients newly diagnosed for uterine cervix cancer, without treatment. METHODS: We determined the catalase activity in blood, reduced glutathione (GSH) in plasma, TBARS and protein carbonyl content from serum samples of the patients. RESULTS: The catalase activity, GSH levels, TBARS and protein carbonyl content had no statistical differences related to the controls, neither when the 2 treatments were compared, possibly because the antioxidant defense may be acting in the first period of the neoplasic transformation, and maybe indicating a possible arrest of the tumor cells caused by the efficiency of the treatments. In the non-treated patients, TBARS and protein carbonyl contents, GSH levels and catalase activity were shown to be increased comparing with the treated patients and compared with the controls indicating an tumor effect on oxidative profile, and the antioxidant activity been increased in the beginning of the tumor development. CONCLUSIONS: We suggest that the treatments were efficient in arrest of the tumor.