The objective of this study was to examine associations of single nucleotide polymorphisms, rs1045642 within the MDR1 gene and rs1799930 within the NAT2 gene, with the risk of colorectal cancer (CRC) in the population of Central Russia. DNA specimens were obtained from 178 patients with CRC (87 males and 91 females) and 327 age-matched healthy controls (179 males and 148 females). Genotyping was performed using real-time PCR. Association of the studied SNPs with the risk of CRC was evaluated using logistic regression analysis. It was demonstrated that MDR1 rs1045642 polymorphism was associated with the increased risk of CRC after correction for gender, age, and smoking (OR = 1.41, 95% CI = 1.09-1.83; P = 0.008). A gender-stratified analysis showed that MDR1 rs1045642 was associated with the increased risk of CRC only in females (OR = 1.62, 95% CI = 1.11-2.35; P = 0.01). In males, no association between MDR1 rs1045642 and CRC was found. Association between MDR1 rs1045642 and the increased risk of colorectal cancer in Russian females from Central Russia was revealed.

Photo-theranostics is a therapeutic and diagnostic approach that uses photosensibilization. This approach makes part of the medicine of the future – subcellular therapy. Photo-theranostics targets cells and tissues that are affected by pathological changes inducing apoptotic cell death. However, the approach allows targeting cellular organelles, if the photo-sensitizing agent is accumulated selectively. Such selectivity can result from the organelle's functional state, as in the case of mitochondria affected by mitochondrial genome abnormalities. For instance, some pro-atherogenic mitochondrial DNA (mtDNA) mutations can lead to mitochondrial dysfunction Some photo-sensitizing agents accumulate selectively in mitochondria making the photodynamic targeting efficient enough. For instance, protoporfyrine IX (PpIX), which is widely used in clinical practice, is produced from a prodrug 5-aminolevulinic acid (5-ALC) in course of heme synthesis cascade in the mitochondria. Exogenous 5-ALC causes excessive formation of PpIX, which cannot be efficiently processed by ferrochelatase and accumulates in the cells. PpIX accumulation directly depends on the cell's metabolic activity. We studied 5-ALC-induced PpIX accumulation on cybrid lines derived from thrombocytes with mutation-bearing mitochondria and THP-1 monocytes devoid of mitochondria. We used 3 cybrid lines and 2 THP-1 monocyte cultures cultured independently by different research groups. The mitochondrial functional state was assessed by fluorescence intensity of mitochondrial dye MitoTracker™ Orange CMTMRos (Thermo Fisher Scientific). Measurement of fluorescence was performed by laser scanning microscopy with spectral unmixing. MitoTracker and PpIX dyes were excited with a 561 nm laser, and fluorescence was measured at 570–750 nm wavelength. The signal was spectrally unmixed to obtain separate MitoTracker and PpIX signals. Individual cells areas were traced on microscopic images taken under identical conditions, and mean values of PpIX and MitoTracker fluorescence intensity were obtained for each cell. We found that PpIX accumulation varied significantly from cell to cell within cell populations. Cybrid lines had increased PpIX accumulation in comparison with original THP-1 monocyte lines. A positive correlation between PpIX amount and mitochondrial membrane potential was observed (Figure 1). Therefore, selective elimination of dysfunctional (mutated) mitochondria can be achieved by adjusting laser intensity sufficient to induce photodynamic destruction of the organelles, while normal mitochondria and the cells as a whole should be preserved at the used light intensities. This work was supported by the Russian Science Foundation (Grant #19-15-00010). Acknowledgement/Funding Russian Science Foundation (Grant # 19-15-00010)

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Aim. To demonstrate the advantages of laparoscopic surgery in patients with colorectal cancer compared to traditional surgical intervention. Methods. A retrospective analysis of 40 patients treatment (the main group) in the Department of abdominal Oncology of the Kursk Regional Oncology Center for the period 20172019, who had a pronounced violation of the passage through the intestine due to stenosing by the tumour, was conducted. As a control group, 30 people who underwent open surgery in the volume of a colostomy for the period 20172019 was taken. Results. According to the average duration of surgical intervention, the groups significantly differed (p 0.05), the average duration of surgery in the laparoscopic group was less 40.513.6 min, with laparotomy 54.518.5 min. The volume of blood loss during the operation was greater in the control group and reached 7540 ml against, 10.55.5 ml the differences were statistically significant (p 0.05). The average length of stay in hospital in the laparoscopic group was 41 days, which is significantly less than in patients who underwent laparotomy 114 days (p 0.05). Postoperative complications occurred in 10% of patients in the control group: seroma of the median wound in 2 patients, ligature fistula in 1 patient. There were no postoperative fatalities in both groups. Conclusion. The comparison of methods of surgical intervention showed that the results of laparoscopic operations are much better than traditional open operations in patients with colorectal cancer since they significantly reduce the duration of the rehabilitation period, accompanied by minor blood loss.