STUDY THE EFFECTS OF IONIZING RADIATION ON THE LEVEL OF CHROMOSOME INSTABILITY IN HUMAN SOMATIC CELLS DURING THE DEVELOPMENT OF TUMOR-INDUCED BYSTANDER EFFECT. / DOSLIDZhENNIa VPLYVU IONIZUIuChOÏ RADIATsIÏ NA RIVEN' KhROMOSOMNOÏ NESTABIL'NOSTI V SOMATYChNYKh KLITYNAKh LIuDYNY PRY ROZVYTKU PUKhLYNO-INDUKOVANOGO EFEKTU SVIDKA.

OBJECTIVE: to determine the impact of the irradiated in vitro blood cells from patients with B-cell chronic lymphocytic leukemia (CLL) on the level of chromosomal instability in peripheral blood lymphocytes (PBL) from healthy persons during the development of tumor-induced bystander effect. MATERIALS AND METHODS: Separate and joint cultivation of PBL from healthy persons (cells-bystanders) together withblood cells from CLL patients irradiated in vitro at the G0 stage of the mitotic cycle by γ-quanta 137Cs in a dose of0.5 Gy 137Cs (cells-inductors) was used. For joint cultivation our own model system for co-cultivation of PBL fromindividuals of different sex, designed by us to investigate the bystander effects at the cytogenetic level was used.Traditional cytogenetic analysis of uniformly painted chromosomes with group karyotyping was performed. The frequency of chromosome aberrations in cells-inductors and cells-bystanders as the markers of chromosome instability were determined. RESULTS: Found that at co-cultivation of PBL from healthy individuals with irradiated blood cells from CLL patientsthe middle group frequency of chromosome aberrations in the bystander cells (5.18 ± 0.51 per 100 metaphases,p < 0.001) was statistically significant higher than its background level determined at a separate cultivaton (1.52± 0.30 per 100 metaphases), and at co-cultivation with non-irradiated blood cells from CLL patients (3.31 ± 0.50 per100 metaphases, p < 0.01). CONCLUSIONS: Co-cultivation of in vitro irradiated blood cells from CLL patients with PBL from healthy persons leadsto an increase in the level of chromosome instability in the bystander cells due to synergism between tumor-inducedand radiation-induced bystander effects.

The contribution of hereditary thrombophilia to increasing the frequency of thrombosis in patients with Ph negative myeloproliferative neoplasms, including the victims from the Chornobyl accident. / VNESOK SPADKOVOÏ TROMBOFILIÏ V ZBIL'ShENNIa ChASTOTY TROMBOZIV U KhVORYKh NA Ph NEGATYVNI MIIeLOPROLIFERATYVNI NOVOUTVORENNIa, VKLIuChAIuChY POSTRAZhDALYKh VNASLIDOK AVARIÏ NA ChORNOBYL'S'KIY̆ ATOMNIY̆ ELEKTROSTANTsIÏ.

OBJECTIVE: The definition of a contribution of the carriage of the G1691A allele of thecoagulation factor V gene and the G20210A allele of the coagulation factor II gene in the development of thrombosis in Ph negative myeloprolifer ative neoplasms (MPN) patients, who were irradiated in the dose range 0,001 0,99 Gy and who were not. MATERIALS AND METHODS: The clinical and molecular genetic characteristics of patients with radiation associated and spontaneous polycythemia vera (PV), essential trombotsytemiya (ET) and primary myelofibrosis (PMF) were ana lyzed. The group of radiation associated PV, ET and PMF represented by 35, 10 and 22 patients respectively, and the cohort of spontaneous PV, ET and PMF - 149, 111 and 78 patients respectively. RESULTS AND CONCLUSIONS: The carriage of any of the two molecular genetic markers of hereditary thrombophilia at spontaneous PMF increases the frequency (3 of 6 vs 8 of 72; p = 0.033) and risk (RR = 6.09; 95 % CI = 1.40-26.43) of thrombosis. The presence of the G1691A allele of the proaccelerin gene in patients with PMF, who were not exposed to ionizing radiation, causes increase the likelihood of venous thrombosis at 10.14 times (95 % CI = 1.67-61.33). At spontaneous and radiation associated Ph negative MPN (in individuals exposed to doses in the range 0,001-0,99 Gy), the higher rate of the occurrence of venous, arterial and any thrombosis was observed in carriers of the G1691A allele the coagulation factor V gene, than in those, whose have the wild type allele. In particular, the G1691A allele of the proaccelerin gene carriers, that are belonged to the group of patients with radiation associated PV, have at 33.33 person years bigger rate of any thrombosis (95 % CI = 0.22-100.00, p = 0.048) and venous vascular events (95 % CI = 12.50-50.00; p = 0.003).In PMF patients with a radiation anamnesis were found the difference (20.00 person years; 95 % CI = 1.51-50.00, p = 0.035) between the ratio of any thrombosis and arterial vascular events, which was calculated for the G1691A allele of the proaccelerin gene and for those, who have the wild type allele. The carriers of the G20210A nucleotide variant of the coagulation factor II gene with spontaneous ET and PMF, compared with patients with the wild type allele, have a higher rate of venous thrombosis per 100 patient years.

Assessment of response to imatinib therapy in patients with chronic myeloid leukemia with e13a2 and e14a2 transcripts of BCR/ABL1 gene. / OTsINKA VIDPOVIDI NA TERAPIIu IMATYNIBOM U PATsIIeNTIV Z KhRONIChNOIu MIIeLOIDNOIu LEYKEMIIeIu Z E13A2 TA E14A2 TRANSKRYPTAMY GENA BCR/ABL1.

OBJECTIVE: Assess the influence of e13a2 and e14a2 transcripts of BCR/ABL1 gene on the efficiency of imatinib ther apy in patients with chronic myeloid leukemia. MATERIALS AND METHODS: We examined 508 patients with the chronic phase of chronic myeloid leukemia without radi ation in anamnesis as well as 13 patients with the similar diagnosis and with confirmed presence of radiation expo sure due to the Chornobyl Nuclear Power Plant accident. RESULTS: No significant differences in hematologic parameters, rate of additional chromosomal aberrations and f vari ant translocations were observed between patients with е13а2 and е14а2 transcript. Cumulative probability of com plete cytogenetic response did not differ in patients with е13а2 and е14а2 transcript and was 76 and 80 % respec tively (р = 0,981). Median of achieving a complete cytogenetic response was 20 months in both patient groups. Significantly more patients with e14a2 transcript compared to patients with e13a2 achieved major molecular response by 12 month of therapy (61.5 % versus 23.0 %, p = 0.016). The higher incidence of deep molecular response by 24 month of therapy was revealed in this group (38.7 % versus 6.25 %, p = 0.018). The overall survival and pro gression free survival rates were not statistically different between two groups with different transcripts. However, the rate of event free survival was statistically lower for the patients with e13a2 transcript compared to the ones with e14a2 transcript (51 % versus 62.0 %, p = 0.039). The number of primary resistant patients was 40 % regardless of the transcript expressed. A significant prevalence in incidence either of lost complete cytogenetic response or fail ure of the major molecular response was shown in patients with e13a2 transcript compared to patients with e14a2 transcripts (43.5 % versus 24.8 %, p = 0.015). CONCLUSION: Imatinib therapy is more effective for CML patients with e14a2 transcript compared to patients with e13a2 transcript expression. The transcript e13a2can be viewed as a adverse prognostic factor for imatinib therapy of chronic myeloid leukemia.

The efficiency of tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia exposed to ionizing radiation due to the Chornobyl nuclear power plant accident. / Efektyvnist'' terapii' ingibitoramy tyrozynkinaz pacijentiv z hronichnoju mijeloi'dnoju lejkemijeju, jaki zaznaly vplyvu ionizujuchogo vyprominjuvannja vnaslidok avarii' na Chornobyl''s''kij AES.

Objective. To study the efficiency of tyrosine kinase inhibitors (TKI) therapy in patients with chronic myeloid leukemia (CML) exposed to ionizing radiation due to the Chornobyl NPP accident, based on the data of cytogenetic and molecular monitoring. Material and methods. 29 CML patients with confirmed radiation exposure due to Chornobyl NPP accident were examined. Of these, 20 patients were treated with imatinib; 103 patients with CML without radiation history treated with TKI were a comparison group. Cytogenetic and molecular genetic disturbances before and on the different stage of TKI therapy were analysed. Results. Additional chromosomal abnormalities as well as special pattern of BCR/ABL transcripts were not revealed in CML patients exposed to ionizing radiation. Complete cytogenetic response (CCR) was shown in 50 and 48.5 % of patients from study and comparison group, respectively. Major molecular response (MMR) was achieved in 20 % of patients with radiation exposure in anamnesis and in 27.6 % of patients from comparison group. The vast majority of CCR and MMR was reached in patients with the pretreatment term up to 6 months, when imatinib was used as a first line therapy. There were less cases of primary imatinib resistance in the same group of patients. In CML patients who had a history of radiation exposure, secondary resistance developed more frequently than in the comparison group and was 25 %. Conclusion. Laboratory monitoring based on the registration of CCR and MMR demonstrated high efficiency of TKI in the CML treatment of patients, exposed due to Chornobyl accident. Extension of pretreatment term leads to the loss of TKI therapy efficiency and increases the likelihood of primary resistance. CML patients exposed to ionizing radiation develop secondary resistence more often than CML patients without radiation exposure in anamnesis.

[Causes of conversion and choice of approach to complete laparoscopic cholecystectomy]. / Prichiny konversii i vybor dostupa dlia zaversheniia operatsii laparoskopicheskoi kholetsistéktomii.

Results of performance of laparoscopic cholecystectomy in 1503 patients were analyzed. In 49 of them application of laparoscopic technology proved to be impossible. The causes, which lead to conversion, were adduced. There was established that in majority of observations an adequate surgical intervention may be performed using minimal laparotomic approach. The conversion is indicated in damage of extrahepatic biliary ducts or in presence of diffuse peritonitis only.