Tatyana Abakumova

The phenotype of peripheral blood neutrophils during the early stage of endometrial cancer

Peripheral blood neutrophils of 123 patients in stage Ia of the endometrial cancer have been assayed. The receptor system and ability of neutrophils to form extracellular traps (NET activity) were assessed by fluorescence microscopy, and spontaneous production of IL-2, IFN-γ, matrix metalloproteinase (MMP), G-CSF was found to exist determined with enzyme-linked immunosorbent assay. Phagocytic and myeloperoxidase activity, the level of cationic proteins, and neutrophil activity were evaluated in an NBT test determining the oxygen-dependent bactericidal action of neutrophils. Topology and rigidity of neutrophil membranes were assessed using scanning probe microscopy. It was established that an increased number of neutrophils was accompanied by changes of their receptor system, aerobic and anaerobic cytotoxicity, enhanced phagocytic activity, and reduced NET activity. The secretory activity of neutrophils changed. An increased level of MMP-1, possibly by enhanced production of reactive oxygen species, reduced IL-2 level, and a drastic increase in G-CSF were observed. The architectonics of neutrophils at stage Ia of endometrial cancer was characterized by altered cell shape and granularity loss. The rigidity of the cell membrane decreased. The changes in neutrophil morphology and persistent hyperactivity suggest the existence of the equilibrium between the immune system and the tumor in stage Ia of endometrial cancer.

Cytokine Status of Serum in Ovarian Cancer Patients with Different Tumor Neoadjuvant Chemotherapy Response

BACKGROUND Polychemotherapy in ovarian cancer (OC) is the second major component of treatment. However, treatment with cytostatics is stopped in 25% of cases because of significant side effects. It is shown that concentration of certain cytokines and their balance is largely formed in accordance with a genetic polymorphism. OBJECTIVE The objective of the study was to evaluate the cytokine status of blood serum of patients with ovarian cancer with different tumor response to neoadjuvant chemotherapy (NACT). METHOD Patients received 2 courses NACT according to the scheme AP. The levels of IL-1β and IL-1Ra, IL-10, TNF-α in blood serum were determined by solid phase ELISA. For molecular genetic studies we selected polymorphic variants in the promoters of the gene represented in dbS`NP NCBI and SNP500 Cancer databases. RESULTS The sharply declined in patients with ovarian cancer compared with the normal, level of IL-1β correlates with increased levels of IL-1RA. It is found that 75% of patients who had progression of the disease after NACT bear CT genotype of gene IL-1β associated with a low expression of the cytokine, while the TT genotype, providing a high level of the expression of IL-1β gene had met only 25% among patients in this group. At the same time 70% of patients with a complete response are the carriers of the T allele, while a complete response was associated with a higher level of IL-1β than in the progression group. Low secretion of TNF-α in all types of tumor response when testing TNF-α G-308A gene polymorphisms was associated with carriage of GA and AA genotypes, which are associated with low production of this cytokine. Increased compared to the control IL-10 production in patients with ovarian cancer associated with genotype replacement at position 1082 G/A IL-10 gene, which occured in 10% of patients with a complete response and 25% of patients with tumor progression after NACT. CONCLUSION All the studied polymorphisms of IL-1β, IL-10 and TNF-α genes in patients with OC are associated with the level of these cytokines and tumor NACT response.

Using Parameters of Protein Oxidative Modifications for Differential Diagnosis of Progressive Ovarian Cancer

Background: The aim of the study was to elaborate a method of specific diagnostics of progressive ovarian cancer. Methods and Findings: We observed 21 parameters in plasma of 300 primary ovarian cancer patients, stage III and IV. Using the least squares method, approximation of the relative frequencies by the Rayleigh distribution density was conducted for each parameter. The likelihood functions were constructed and intervals for each measurement on each stage were determined. Approximation accuracy was identified while checking the hypothesis of correspondence of parameter practical value to the theoretical law of density distribution by Pearson criterion. Conclusions: The obtained results suggest that the level of the oxidative modification of proteins may serve as a reliable indicator for the differential diagnosis of stages III and IV ovarian cancer.

The effect of picosecond laser pulses on redox-dependent processes in mice red blood cells studied in vivo

The study highlights the effect of different modes of in vivo laser irradiation of mice using a PFL8LA laser with λ = 1560 nm, pulse duration of 1,4•10-12 s, peak power of 3,72•103 W and average output power of 20•10-3 W on the lipid peroxidation parameters: conjugated dienes, ketodienes and conjugated trienes, malondialdehyde, Schiff bases and the activity of antioxidant enzymes - catalase, glutathione -S-transferase and superoxide dismutase in erythrocytes and plasma of mice. Two groups of mice received a total dose of 3.8 J/cm2 per group, but the 1st group was irradiated only once, while the 2nd – four times. Significant differences in the parameters of the 1st and 2nd groups indicate different effects of the irradiation modes on redox-dependent processes in red blood cells of mice.

OXIBIOTIC CYTOTOXICITY OF NEUTROPHILS OF PERIPHERAL BLOOD AFTER THE POLYCHEMOTHERAPY AT THE CANCER OVARIAN

Abstract. For the purpose of an assessment of influence of chemotherapy by САР scheme on aerobiotic cytotoxicity in neutrophils of peripheral blood of 43 primary patients with cancer ovarian at the III‐IV clinical stages on FIGO the level myeloperoxidase and activi‐ty in the spontaneous NST‐test was determined. Cages were allocated from a blue blood on a double gradient fikoll‐urografin (ρ = 1,117 and 1,077 g/ml). Comparison of the quantitative variables corresponding to normal distribution was carried out by means of Studentʹs test. Results are presented in the form of average cytochemical coefficient. The patients passable inspection and treatment in Ulyanovsk in regional clinical oncological clinic, received a polychemotherapy course, according to САР scheme. Indicators of aerobiotic cytotoxici‐ty, absolute and relative quantity of neutrophils of peripheral blood were defined till 3 days after introduction of chemotherapeutic agent. As a result of the conducted researches it is established that in the patients at the IV clinical stage on FIGO the increased to poly‐chemotherapy absolute and relative quantity of neutrophils decreases and practically the indicators characterizing aerobiotic cytotoxici‐ty donʹt change. In the patients at the III stage of a cancer ovarian on FIGO increase of absolute and relative quantity of neutrophils at simultaneous decrease in indicators myeloperoxidase and NST‐test takes place. The obtained data testify to need of individual monitor‐ing of reactivity of neutrophils at suffering from cancer ovaries at the III‐rd stage of a disease after the first course of polychemotherapy according to CAP scheme.

Trigger effect of infrared femtosecond laser irradiation on neoplasm in experimental cervical cancer

The present work discusses effect of infrared (IR) femtosecond laser irradiation on neoplasm of white mice with experimental cervical cancer- 5 (CC-5 on the 20th and 30th days after tumor transplantation). Tumor tissue was irradiated by femtosecond erbium doped fiber laser: the wavelength is 1.55 μm, average and peak powers are1,25 mW and 6kW, respectively, irradiation trials n=10. The average energy density (energy dose) on a tissue for two groups of animals was 0,24 J/cm2 and 0,36 J/cm2 for a single trial. Irradiation was followed by biochemical determination of LPO AOS parameters (“Lipid peroxidation-antioxidants” system): malondialdehyde (MDA), activity of superoxide dismutase (SOD), catalase and glutathione-reductase (GR), glutathione-S-transferase (GST). A subsequent morphological study of tumor tissue was performed. Mathematical analysis of data demonstrates a weak dependence of the studied parameters on energy dose. The latter implies the trigger effect of IR femtosecond laser irradiation on redox-dependent processes in neoplasm at experimental cervical cancer.

Neutrophils of the patients with cervical cancer after femtosecond laser radiation in vitro

The cytochemical analysis of the aerobic and anaerobic bactericidal, phagocytic activity, phagocytosis completeness, as well as membrane topology and rigidity has been performed with the Scanning probe microscopy (Solver Pro, NT-MDT, Russia) in neutrophils of the patients with cervical carcinoma treated with the Erbium laser radiation at different intensity. The obtained data reveal a significant effect of the femtosecond laser radiation on neutrophil morphofunctional state in patients with cervical cancer. The efficiency of the femtosecond radiation depends on its intensity and clinical stage of the cervical cancer.

Effects of femtosecond laser radiation on blood cell suspensions

In the present work the effects of high-power femtosecond laser irradiation on a functional condition of red blood cells and neutrophils in vitro have been investigated. The data on parameters of the lipid peroxidation - antioxidants system, hemoglobin level and rigidity of red blood cell membranes testify destabilization of the membranes under the influence of the given laser. The study of phagocytic activity, anaerobic and aerobic metabolism of neutrophils, and rigidity of their membranes allows to suppose the dose-dependent effect to be stimulating.