METABOLISM OF ADJACENT ADIPOSE TISSUE AND BODY MASS OF THE PATIENTS WITH STAGE III–IV COLORECTAL CANCER
Keywords:
colorectal cancer, obesity, metastasis, nitric oxide, superoxide radicals, free fatty acids.Abstract
Summary. Obesity is a pathological accumulation of hypertrophied adipocytes, which may be an unfavorable
factor in the formation of tumor cell chemo-resistance
and the progression of malignant neoplasms (local relapses, metastases). A critical molecule that influences the growth and metastasis of tumors is nitric oxide
ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ
ОНКОЛОГИЯ • Т. 20 • № 3 • 2018 211 211
(NO), which can damage DNA, suppress the DNA repair enzymes, regulate apoptosis and metastasize. Proliferation of tumor cells, angiogenesis, metastases are
closely related to the functioning of NO and superoxide
radicals (SR). Objective: to investigate the levels of NO
and SR in adjacent adipose tissue (AAT), as well as the
concentration of free (un-esterified) fatty acids (FFA)
in the blood of patients with colorectal cancer (CC) stage
III–IV, depending on the weight of the patient’s body,
degree tumor differentiation, volume of metastases (M)
in the liver. Object and methods: samples of AATs of patients with CC of the III–IV stage with obesity (body
mass index (BMI) > 25; n = 84) and without its signs
(BMI < 25; n = 47). For control (normal adipose tissue — NAT) considered the material from 18 patients
with benign neoplasms. The rate of generation of SR by
mitochondria and the NO level in the samples of the
adipose tissue were determined by the method of electron paramagnetic resonance (EPR) at room temperature and at low temperature using appropriate spin
traps. The content of FFA in blood was determined by
spectrophotometric method at λ = 546 nm. Results: the
activity of FeS-proteins of the electron transport chain
(ETC) of mitochondria in the AATs of patients with CC
(BMI > 25) was significantly higher compared to that
in NAT; the level of ubisemichinon in AAT was 11 times
higher than that of NAT. An increase in the level of activity of molybdenum-containing enzymes (xanthine and
aldehyde oxidase) was also observed in AATs of patients
with CC, indicating accumulation of toxic products of
decomposition of purines and aldehydes in it. The level
of SR in AAT patients with CC with BMI > 25 was 5.6
and 1.3 times higher than in the NAT and in patients
without obesity (BMI 18.5–25), respectively. The level
of NO in AAT patients with BMI > 25 was significantly
lower in comparison with NAT, in AAT of patients without obesity did not differ from such in NAT (p > 0.05).
The level of FFA in the blood of patients with CC, regardless of the presence of signs of obesity (with BMI
18.5–25 and > 25), exceeded this indicator in donors
(BMI >25) by 3.4 and 6.0 times, respectively (p<0.05).
In the adipose tissue, adjacent to the G1–2- and G3-
tumors, NO levels were significantly different, however, they were lower in 2.0 and 2.5 times than in NAT
(p < 0.05). In patients with morbid obesity (BMI > 40)
the average volume of M was 19.75 ± 5.9 cm3
. Volume
M was significantly lower in patients with BMI < 40: at
BMI 18.5–24.9 was 4.33 ± 2.6 cm3
, with BMT 25–
40 — 8.40 ± 3.7 cm3
. Conclusions: the severity and direction of changes in a number of characteristics of the
adipose tissue of patients with CC of III–IV stage (spectra of AAT EPR, NO and SR levels in AAT compared
with NAT, the concentration of FFA in blood) has an
indisputable link with the weight of patients: in the presence of different degrees of obesity metabolic disorders
increase. In patients with morbid obesity, the largest
volume of M in the liver was observed. Based on the
results obtained, selective NO-dependent regulation of
ETC in mitochondria, in particular, in AAT, to influence energy expenditure can be an effective component
in the strategy of treatment of patients with CC.
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