PROGNOSTIC VALUE OF BLOOD REDOX-STATE INDICATORS IN PATIENTS WITH BREAST CANCER
Keywords:
breast cancer, hormone receptor status, blood redox-state, superoxide radicals, nitric oxideAbstract
Summary. Objective: to investigate the level of ceruloplasmin (CP), transferrin (TF), NO-hemoglobin (NO-Hb), methemoglobin (MetHb), superoxideand NO-generating activity of neutrophils and matrix metalloproteinases-2 and -9 (MMP-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 (SR) 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 — diethyldithiocarbamate). 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 MMP-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 ubisemiquinones 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 SR 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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