Prognostic value of blood redox-state indicators in patients with breast cancer
Summary. Introduction. In women of postmenopausal age plasma circulating levels of estrogens and their levels in mammalian glands reduced. However, breast cancer rate in this cohort remains to be high meaning the presence of other damaging factors. Capacity of estrogens and their metabolites to change the balance in redox-state of organs and blood though the increase of superoxide radicals generation rate which in turn have signaling and damaging effects is a factor of high importance. Numbers of data show that oxidative metabolism of estrogens leads to catechol estrogen-3,4-quinones formation and this has a great potential in breast cancer initiation. Objective. Тo investigate the level of ceruloplasmin (CP), transferrin (TF), NO-hemoglobin (NO-Hb), methemoglobin (MetHb), superoxide- and NO-generating activity of neutrophils and matrix metalloproteinases-2 and -9 in the blood of patients with breast cancer in connection with the hormone receptor status of tumors of patients with breast cancer in ІІ–ІІІ stages. Object and methods. Blood samples were studied in patients with breast cancer II–IIІ stages in reproductive and postmenopausal age. The level of CP, TF, «free» iron, hemichromes, MetHb, NO-Hb, and ubisemiquinone was investigated by the method of electron paramagnetic resonance (EPR) in a low-temperature mode (77 K). The rate of generation of superoxide radicals by neutrophils was determined by EPR method at room temperature using the spin capture TEMPONE-H («Sigma»). The NO-generating activity of blood neutrophils was determined by the EPR method using Spin Traps technology at a temperature of 77 K (spin trap — diethyldiothiocarbamate). The level of active forms of gelatinase in serum was determined by zymography in a polyacrylamide gel. Results. In patients with reproductive and postmenopausal age with ER(+)/PR(+) and ER(–)/PR(–)-status, the level of CP exceeded the values characteristic of donors, and the level of TF in them was significantly lower than control. An increase in NO-Hb content in blood was observed, this indicator was highest in postmenopausal patients with ER(–)/PR(–)-status and directly correlated with NO-generating activity of neutrophils (r=0.56; p<0.05). The activity of matrix metalloproteinase-9 in the serum of patients with ER(–)/PR(–)-status in 3.3 times significantly exceeded that for patients with ER(+)/PR(+)-status. In the blood of 78% of patients with postmenopausal breast cancer with the status of tumors with ER(–)/PR(–), increased content of estrogen metabolites — quinones and ubisemiychinones was observed. The level of the latter was directly correlated with the stage of the tumor process (r=0.58; p<0,05). It has been established that neutrophils in the blood of patients of reproductive age with ER(+)/PR(+) and ER(–)/PR(–)-status of tumors generate superoxide radicals with a rate 9 and 18 times higher compared to donors, respectively, and NO — more than 12 times in both subgroupes. Conclusion. Reactions of the redox state of the blood in patients with breast cancer, whose changes depend on the hormone receptor status of the tumors, in particular ER(+)/PR(+) and ER(–)/PR(–), are revealed.
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