Search

Numerous studies have proven the high resistance of cancer stem cells (CSCs) to a single-dose low-LET ionizing radiation exposure in vitro. These data are the basis for the assumption about the important role of CSCs in cancer recurrence after conventional radiation therapy. However, the patterns and mechanisms of fractionated radiation effects on this population of cells have not been studied enough, and there are only a few publications regarding cervical cancer. Therefore, the purpose of this work is to elucidate the quantitative changes in the CSC population after low-LET radiation exposure using the conventional fractionation regimen in vitro (in cervical cancer cell lines HeLa and SiHa) and in vivo (in cervical scrapings from patients with squamous cell cervical cancer during radiation therapy). Using flow cytometry, the proportion of CSCs was measured in these cell lines after each dose fraction until a cumulative dose of 10 Gy was reached, and in clinical samples of 26 patients before treatment and after irradiation at a cumulative dose of 10 Gy to point A. CSCs were identified in cell cultures by the ability of these cells to pump out the fluorescent dye Hoechst 33 342 and form a side population (SP) and in cervical scrapings by the CD44+CD24low immunophenotype. A statistically significant increase in the proportion of CSCs was found after fractionated irradiation of cervical cell cultures in the range of 2–10 Gy, as compared with the nonirradiated control. High individual variability in the proportion of CD44+CD24low CSCs was detected in cervical scrapings before treatment and after radiation exposure. An irradiation-induced increase in this indicator was observed in 38% of patients; in other patients, a decrease in this indicator was found after irradiation at a cumulative dose of 10 Gy or its preservation at the initial level. A high inverse correlation was observed between the CSC proportion before treatment with its change after irradiation (R = –0.71; p < 0.0001). The results indicate significant individual differences in the response of cervical CSCs to radiation treatment and substantiate the fundamental possibility of further investigation of the prognostic significance of CSC quantitative changes after the first sessions of radiotherapy with regard to the short- and long-term results of treatment.

Objective: to improve the assessment of activity of ulcerative colitis and the ability to predict the development of relapse of the disease, as well as the selection of adequate therapy.Materials and methods: the study included 90 people: 70 patients with ulcerative colitis and 20 healthy volunteers. The disease activity was evaluated using 7 disease activity indices. The expression of matrix metalloproteinase -9 (MMP-9) in the colon mucosa was evaluated by immunohistochemistry.Results: data were obtained on the activity of MMP-9 in colonobioptates in patients with ulcerative colitis with varying degrees of disease severity, which complements our knowledge of the pathogenetic mechanisms of UC and, based on the developed mathematical model, allows predicting the development of recurrence of UC. Based on the analysis of clinical indices of UC activity, an algorithm for evaluating the effectiveness of basic therapy has been developed.Conclusion: tools are provided to improve the prognosis of UC relapse, and a personalized approach to evaluating the effectiveness of the alternatives of drug therapy is developed.

The presence of virus DNA integration into the cell genome was studied for 47 primary HPV16-positive patients with morphologically verified stage III cervical cancer. By using ROC analysis, the patients were divided into two groups: with and without HPV DNA integration into the host cell genome. The differences between the groups by the histological type, degree of tumor differentiation, and primary response to therapy were statistically insignificant. Virus DNA integration more than 7-fold reduced 5-year relapse-free survival and 1.7-fold reduced overall survival rate in comparison with patients without HPV DNA integration (p=0.0002 and p=0.05, respectively). The relative risk of adverse outcome of the disease in patients with the presence of HPV16 DNA integration increases by 4 times over a period of less than 3 years (р=0.0006) at high AUC level. The probability of earlier progression of the disease in patients with of HPV DNA integration calculated according to the Cox proportional hazards model was 85.5% (hazard ratio 5.96; p=0.002). Thus, the results suggest that the presence of HPV16 DNA integration into the cell genome is an independent factor in predicting clinical outcome of advanced cervical cancer and can serve as an effective criterion for the individual choice of treatment tactics for the patients.

The proportion of CD44+CD24low cancer stem cells (CSC) was determined in cervical scrapings of 41 patients with squamous cell carcinoma of the uterine cervix before treatment and after irradiation in a total focal dose of 10 Gy. The relationship of quantitative changes in the CSC population with such parameters of papillomavirus infection as genotype, viral load, and physical status of HPV DNA (the absence or presence of HPV DNA integration into the cell genome and the degree of integration) was studied. Single- and multi-factor analysis revealed 2 independent indicators affecting the radiation response of CSC: initial number of these cells before treatment and physical status of HPV DNA. The increase in the CSC proportion after radiation exposure was observed 4.5-fold more often in patients with an initially low proportion of CSC (

Prognostic significance of the proportion of cancer stem cells in cervical scrapings from 38 patients with uterine cervical cancer before treatment and after irradiation in a total dose of 10 Gy was assessed for immediate results of radio- and combined chemoradiotherapy evaluated by the degree of tumor regression in 3-6 months after the treatment. Cancer stem cells were detected as cells with CD44+CD24low immunophenotype by flow cytometry. The proportion of cancer stem cells in patients with the complete tumor regression decreased by on average 2.2±1.1% after irradiation, while in patients with partial regression this indicator increased by on average 3.3±2.3% (p=0.03). Multiple regression analysis revealed two independent indicators affecting tumor regression: the stage of the disease (which is quite expected) and change in the proportion of cancer stem cells after the first irradiation sessions (R=0.60, p

The ROS concentration and proliferation activity (Ki67 expression.marker) have been studied in the periphery blood lymphocytes of Moscow and Obninsk citizens, donors, Chernobyl disaster liquidators, inhabitants of the region contaminated after Chernobyl disaster (Klincy) and individuals with prostate cancer. It was shown that ROS concentration in lymphocytes of the liquidators and residents of the polluted region was lowered. But in lymphocytes of patients with tumors the ROS content was higher in comparison with the control. The cell content with Ki67 expression in lymphocytes of the individuals resided in the polluted region and tumor patients was lowered.

The aim of this study is to assess the level of somatic mutagenesis according to the frequency of lymphocytes bearing mutations at the locus of T-cell receptor (TCR) in the residents of the Bryansk region contaminated with radionuclides as a result of the Chernobyl accident. The study was :conducted in 2014 in two regional centers - Klintsy and Novozybkov (average¹³⁷Cs pollution density of 322 and 708 kBq/m²,.respectively). The average frequency of the TCR-mutant cells in the total group of examined residents of the Bryansk region (n = 237) was not significantly different from that in the group of agematched control persons living in un- contaminated areas (n = 146): 3.8 x 10⁻⁴ vs 3.5 x 10⁻⁴, respectively (p = 0.84). However, after separation of examinees into 3 groups depending on age at the start of irradiation (at.the moment of the Chernobyl acci- dent) it was found that the average frequency of the TCR-mutant cells in the persons exposed in utero was 1.6 higher than that in the control group (p = 0.04). Proportion of persons with an increased frequency of the mutant cells (more than the age norm of this indicator) among prenatally exposed population reached 23.8%; which was about.4 times higher than in the control group (p = 0.04). Proportion of persons with an increased frequency of the TCR-mutant cells in group "0-17 years at the start of irradiation", was about 2 times higher than in controls, but this difference was not statistically significant (8.0% vs 4.3%, respectively, p = 0.33). In the third group "18 or more years old at the start of irradiation" we could not register the difference in the average frequency of theTCR mutant cells or the proportion of persons with an increased frequency of these cells in comparison with the age-matched control group. In general, comparison with earlier data shows that age-related regularities of somatic mutagenesis established 15-18 years after the Chernobyl accident persist at a later date (after 28 years in this study).