SUPEROXIDE- AND NO-DEPENDENT MECHANISMS OF FORMATION OF METASTATIC MICROENVIRONMENT DISTANT SITES OF METASTASIS IN PATIENTS WITH COLORECTAL CANCER
Keywords:
metastatic colorectal cancer, liver, redox state of distance metastasis sites.Abstract
Summary. Objective: to study the peculiarities of the
redox state of metastasis (M), liver tissue (LT), blood
and urine of patients with metastatic colorectal cancer
(mCRC) in liver. Object and methods: a study of the tissue M; LT, which is in direct contact with M; LT taken at
a distance of 5 cm from M; urine and blood of 25 mCRC
patients with liver damage was carried out. The activity of iron-sulfur protein N-2 (FeS-protein N-2) electrontransport chain (ETC) of mitochondria, the level
of lactoferrin (LF), free iron (FI) was determined by
the method of electron paramagnetic resonance (77 K).
The rate of superoxide radicals (SR) and nitric oxide
(NO) were detected according spin trapping technique
(Spin Traps). The activity of matrix metalloproteinases (MMP-2 and -9) was registered using method of zymography in polyacrylamide gel. Results: in mCRC with
liver M functioning of cytochrome P450 in hepatocyte
detoxification system, defects in ETC of mitochondria
(NO complexes with FeS-proteins — NOFeS-proteins),
metabolism disorder of oxygen and iron, changing the
degree of degradation of extracellular matrix. The most
severe of these violations were in the LT, which is adjacent to M (plot formation of metastatic microenvironment) that manifested decreased levels of cytochrome
P450, increasing levels of NOFeS-proteins complexes,
LF, FI, MMP-2, -9 and speed generate CP and NO
comparable to TP at 5 cm of M. In blood of patients with
mCRC was found high (compared with patients without
M CRC) level superoxyde- and NO-generating activity
of neutrophils, active forms of gelatynases. Conclusion:
the investigated parameters redox state of liver of patients
operated on mCRC can be used to assess the functional
state of organs and tissues distant M, risk of recurrence
cancer and improve therapeutic approaches.
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