Role of the adipose tissue in the rectal cancer microenvironment
Summary. Introduction. Over the past ten years, our understanding of the mechanisms of the influence of adipose tissue (AT) on tumor progression has improved significantly, however, mechanisms for the interaction of adipocytes with the cells of rectal cancer (RC) in the conditions of radiation and chemo-radiation therapy have not been revealed until now. Methods. A prospective randomized single-centered study was conducted. The study involved 110 patients with locally advanced rectal cancer (LA-RC; ymrT3–4aN0–2M0–1, CRM-positive) overweight in the period from January 2016 to December 2018. Patients were randomized to a ratio of 1:1 to the main group (group A; n=57; radiotherapy with a total focal dose of 50.4 Gy (1.8 Gy × 28) and oxaliplatin based chemotherapy), and on the comparison group (group B; n=53; radiotherapy a total focal dose of 50.4 Gy (1.8 Gy × 28) and chemotherapy based on fluoropyrimidines). Results. The reported levels of superoxide radical in the contacting with the tumor were 0.58±0.15 (group A) and 0.70±0.12 nmol/g tissue·min (group B) (p<0.001). In the blood of these patients, the increase in the level of free fatty acids was found: in group A to values of 2.05±0.15 mmol/l, and in group B this indicator was 2.48±0.20 mmol/l at the values of norm 0.57±0.11 mmol/l. The levels of 8-oxoguanine in patients of the studied groups did not have statistically significant differences — 0.80±0.08 and 0.84±0.13 respectively for groups A and B (p=0.052). Conclusions. The AT adjacent to the tumor is an energy depot that can act as a promoter of tumor progression, providing the tumor of LA-RC by an energy substrate — free fatty acids. The use of oxaliplatin based chemotherapy reduced the level of oxidative-induced point mutations in the adipocyte DNA of the AT.
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