Classical and up-to-date models of hematopoietic Lineage determination are briefly reviewed with the focus on myeloid-based models challenging the existence of the common progenitor for T cells, B cells and NK cells. The analysis of immunophenotype of leukemic blast cells seems to be a promising approach for interpreting some controversies in the schemes of normal hematopoiesis. The literature data as well as our own findings in the patients with various types of acute leukemias are in favor of the concept postulating that common myeloid-lymphoid progenitors giving rise to T and B cell branches retain the myeloid potential. The similarity of some immunophenotypic features of blast cells in pro-B acute lymphoblastic leukemia and acute monoblastic leukemia is consistent with monocyte origin postulated in the studies of normal hematopoiesis. Study of acute leukemias may be the challenging area of research allowing for new insight into the origin of hematopoietic cell lineages.

In recent years, the new direction such as identification of informative circulating markers reflecting molecular genetic changes in the DNA of tumor cells was actively developed. Smoking-related DNA adducts are very promising research area, since they indicate high pathogenetic importance in the lung carcinogenesis and can be identified in biological samples with high accuracy and reliability using highly sensitive mass spectrometry methods (TOF/TOF, TOF/MS, MS/MS). The appearance of DNA adducts in blood or tissues is the result of the interaction of carcinogenic factors, such as tobacco constituents, and the body reaction which is determined by individual characteristics of metabolic and repair systems. So, DNA adducts may be considered as a cumulative mirror of heterogeneous response of different individuals to smoking carcinogens, which finally could determine the risk for lung cancer. This review is devoted to analysis of the role of DNA adducts in lung carcinogenesis in order to demonstrate their usefulness as cancer associated markers. Currently, there are some serious limitations impeding the widespread use of DNA adducts as cancer biomarkers, due to failure of standardization of mass spectrometry analysis in order to correctly measure the adduct level in each individual. However, it is known that all DNA adducts are immunogenic, their accumulation over some threshold concentration leads to the appearance of long-living autoantibodies. Thus, detection of an informative pattern of autoantibodies against DNA adducts using innovative multiplex ELISA immunoassay may be a promising approach to find lung cancer at an early stage in highrisk groups (smokers, manufacturing workers, urban dwellers).

Evidence indicates that prolactin plays a crucial role in the normal function and development of the prostate, but abnormal high levels of the hormone are associated with hyperplasia and cancer of the gland. Aims: the present study was designed to describe the progressive specific histological abnormalities in the prostate of rats with chronic hyperprolactinemia. Prolactin was administered during 4; 12 or 24 weeks, and the resulting prostatic alterations were compared with control rats, and also with those treated with testosterone, or the combination of prolactin + testosterone. Rats treated with prolactin, testosterone or prolactin + testosterone expressed precancerous histological abnormalities in the dorsolateral and ventral portions of the prostate as early as in 4 weeks of treatment, but in all cases the malignancy increased after 12 or 24 weeks of treatment. Conclusion: our study confirms that chronic hyperprolactinemia is a cause of prostate precancerous pathologies.

Aim - to study indices of energy metabolism, content of K<^>+ and Mg<^>++ both in peripheral blood and in Walker-256 carcinosarcoma during development of resistance to doxorubicin. Methods: Resistance of Walker-256 carcinosarcoma to doxorubicin has been developed through 12 subsequent transplantations of tumor after the chemotherapy. Parental strain was inhibited by drug by 65 %, while transitional resistant substrains - by 30 % and 2 %, respectively. Determination of biochemical indices in blood serum and homogenates of tumor tissue, level of potassium, magnesium, lactate, glucose, activities of lactate dehydrogenase and glucose-6-pbosphate dehydrogenase was performed with the help of biochemical and immune-enzyme analyzer GBG ChemWell 2990 (USA) using standard kits. Polarography was used to determine indices of mitochondrial oxidative phosphorylation. Study of mitochondrial membrane potential was carried out on flow cytometer Beckman Coulter Epics XL using dye JC-1. Results: It has been determined that development ofdrug resistance causes the decrease of K<^>+, Mg<^>++, glucose content in blood serum and increase of these indices in tumor tissue. At the same time, gradual tumorіs loss of sensitivity is characterized by decrease of glycolysis activity in it and activation of mitochondrial oxidative phosphorylation and pentose phosphate pathway of glucose degradation, which causes more intensive formation of NADPH. Conclusion: development of drug resistance of tumor causes certain metabolic changes in organism and tumor. Further study of such changes will make possible to determine tumor and extratumor markers of resistance.

Aim - to evaluate potential of Naphthal-NU, Napro-NU and 5-Nitro-naphtlial-NU, 2-chloroethyinitrosourea compounds with substituted naphthalimide in the preclinical studies. In vitro cytotoxicity of three nitrosoureas was determined in human and mouse tumor cell lines by MTT assays. In vivo antitumor potential was evaluated in Sarcoma-180 (S-180) and Ehrlichіs carcinoma (EC) solid tumors. Apoptosis in S-180 cells was analyzed by using Annexin V-Propidium Iodide (PI). Histological analysis of liver and kidney was performed at optimum dose (50 mg/kg). Expression status of CD4<^>+, CD8<^>+ and CD25<^>+ cells in treated mouse were also examined. Significant tumor growth retardation by the compounds was noted in early and advanced disease groups, as the life span of drug treated mice increased considerably. Drug induced killing was observed by induction of apoptosis. Naphthal-NU and 5-Nitro-naphthal-NU were effective to normalize the tumor induced structural abnormalities of liver and kidney. The compounds have no immunotoxic effect on CD4<^>+ and CD8<^>+ T cells and down regulate CD4<^>+CD25<^>+ regulatory T cells. Conclusion: overall data holds promise for the antitumor activity with lower toxicity of the compounds that can be utilized for the treatment of human malignant tumors.

Aim - to study antitumor activity of triptorelin - agonist of gonadotropin-releasing hormone and exemestane - inhibitor of aromatase in combination with cisplatin on the model of receptor-positive for estrogens and progesterone malignant transplantable ascites ovarian tumor (OT); to assess tumor response to treatment and VEGF expression in tumor cells under different combinations of cytostatic and hormonal drugs. 36 female Wistar rats, which underwent intraperitoneal transplantation of ascites OT (<$E5~times~10 sup 6> cells per animal), have been involved in the study. Rats were distributed into 4 groups (9 rats in each group): group 1 - animals, which received combination of cisplatin and triptorelin; group 2 - rats treated with combination of cisplatin and exemestane; group 3 - animals, which were administered with combination of cisplatin, triptorelin and exemestane; group 4 - rats, which received combination of triptorelin and exemestane. Histological study with assessment of treatment pathomorphosis in OT and immunohistochemical study have been carried out to analyze VEGF expression in OT cells. Survival of animals has been evaluated. Combination of cytostatic agent with triptorelin or exemestane has demonstrated significantly higher rates of treatment pathomorphosis (10,1 +- 0,1 % and 16,2 +- 0,3 %, respectively) and antiangiogenic activity in OT (21,4 +- 1,4 % and 15,0 +- 1,3 %, respectively), as well as the highest survival of animals (100,0 and 85,7 %, respectively) as compared with the same in rats treated in regimen of monotherapy with cisplatin, triptorelin, exemestane or by combination of hormonal drugs. Among animals treated by combination of cytostatic drug with triptorelin, two were cured (22,2 %), and among rats, which received cisplatin and exemestane, one animal (11,1 %) was cured. Conclusions: triptorelin and exemestane increase antitumor activity of cisplatin in respect to the transplantable malignant ascites OT and significantly increase survival of animals, especially when triptorelin and cisplatin are used in combination.

Study was aimed to analyze the dynamics of changes and study interrelations between content of ferritin, transferrin, active gelatinases (MMP-2 and -9) in blood serum and tumor tissue, free iron, rate of superoxide radicals generation in tumor, activity ofNADPH-oxidase and iNOS in neutrophils rats with sensitive and resistant strains of Guerin carcinoma (GC). In order to obtain resistant tumor, 12 courses of cisplatin chemotherapy have been carried out on rats bearing GC. Levels of transferrin and free iron were determined by analysis of EPR spectra from computerized radiospectrometer EPR RE-1307 at temperature of liquid nitrogen. Rate of superoxide radicals and nitric oxide generation in tumor and neutrophils of blood was determined by EPR using spin traps at room temperature. Content of ferritin in tumor homogenate and blood serum of rats with GC was determined by ELISA method using corresponding kits. Concentration of active forms of MMP-2 and -9 in obtained samples was determined using method of zymography. Unregulated generation of superoxide radicals and NO by mitochondria of tumor cells and NADPH-oxidase and iNOS neutrophils via oxidation of iron-containing proteins causes the accumulation of "free iron" complexes in blood and tumor tissue of rats able to evoke oxide-induced damages of macromolecules. It has been shown that for resistant strain of carcinoma, as compared with sensitive one, significantly higher concentrations of active forms of MMP-2 and -9 in blood serum of rats are typical. Dynamics of gelatinases activity changes in tumor tissue corresponds in general with dynamics of changes in serum. In tumor tissue of rats the indices of gelatinases activity positively correlate with rate of superoxide radicals generation, content of "free iron" complexes, ferritin and activity of transferrin. Cytostatic agent increased levels of reactive oxygen species (ROS) and self-amplify rate of superoxide radicals generation. In turn, activation of MMPs via superoxide-depending regulation allows tumor ceils to facilitate migration, invasion and finally - formation of metastatic centers. Mentioned above tumor "oxide phenotype" determines high level of its aggressiveness and forms corresponding level of drug resistance. Conclusions: Thus, high levels of superoxide radicals oxidize transport proteins and form free iron pool. Iron ions, via Haber - Weiss mechanism, initiate generation of the hydroxyl radicals, which also enhance oxidation processes.

The aim of this study was to investigate the reaction of normal and tumor cells to genotoxic effect of widespread environmental factors - exogenous nitric oxides and ionizing radiation. The animals were treated with NO (125 mg/m<^>3) and low dose ionizing radiation (10 acute exposures with 0,1 Gy each). Genotoxicity was estimated in vivo in rats peripheral blood lymphocytes, bone marrow cells and tumor cells of Guerin carcinoma. DNA damages were assessed by alkaline single-cell gel electrophoresis. Exogenous nitric oxides as well as irradiation caused significant increase of DNA damage in all types of investigated cells. The genotoxic effect increased in the order: peripheral blood lymphocytes << bone marrow cells << Guerin carcinoma cells. The greatest genotoxic effect was registered in Guerin carcinoma cells on terminal phase of tumor growth in rats exposed to NO and low dose ionizing radiation. Conclusions: long-term exposure to common environmental factors (exogenous nitric oxides and ionizing radiation) capable to induce DNA damage in different cells. Severity of the genotoxic effect depends on ceil type and nature of impacting factors. NO caused more significant DNA damage than low dose ionizing radiation, but the highest level of DNA damage was observed after their joint action. Obtained results confirm the real threat of cancer risk increase under combined action of common environmental factors of diffіrent nature.

Endometrial cancer (EC) is the second most common malignancy associated with hereditary non-polyposis colorectal cancer (HNPCC) family. The development of HNPCC is associated with defects in DNA mismatch repair (MMR) pathway resulting in microsatcllite instability (MSI). MSI is present in a greater number of EC than can be accounted for by inherited MMR mutations, therefore alternative mechanisms may underline defective MMR in EC, including polymorphic variation. Aim: we checked the association between EC occurrence and two polymorphisms of MMR genes: a 1032G>>A (rs4987188) transition in the hMSH2 gene resulting in a Giy22Asp substitution and a - 93G>>A (rs 1800734) transition in the promoter of the hMLHl gene. Material and methods: These polymorphisms were genotyped in DNA from peripheral blood lymphocytes of 100 EC patients and 100 age-matched women by restriction fragment length polymorphism PCR. A positive association (OR 4,18; 95 % CI 2,23 - 7,84) was found for the G/A genotype of the -93G>>A polymorphism of the hMLH 1 gene and EC occurrence. On the other hand, the A allele of this polymorphism was associated with decreased EC occurrence. The Gly/Gly genotype slightly increased the effect of the -93G>>A-G/A genotype (OR 4,52; CI 2,41 - 8,49). Our results suggest that the -93G>>A polymorphism of the hMLH 1 gene singly and in combination with the Gly322Asp polymorphism of the hMSH2 gene may increase the risk of EC.

Aim - to evaluate the association between the presence of CD8 and CD45RO T lymphocytes in bone marrow (BM), disseminated tumor cells (DTCs), tumor hypoxia and their impact on disease outcome. 91 naive gastric cancer (GC) patients were enrolled into the study. DTCs, CD8- and CD45RO-positive T lymphocytes in BM were detected using immunocytochemistry. Ail patients were thoroughly informed about the study that was approved by the local ethics committee. Statistical analyses were done using NCSS2000/PASS2000 and Prism, version 4.03 software packages. It was detected that 80,5 and 81,3 % of patients had CD8- and CD45RO-positive T cells in BM, respectively. When DTCs were detected in BM, the number of patients with CD8-and CD45RO-positive T cells in BM were 86,1 and 84,4 %, respectively. It was also determined, that the number of patients with DTCs in BM with categories M0 and M1, and with CD8- and CD45RO-positive T cells in BM were 86,2 and 85,7 %, 85,7 and 80,0 %, respectively. The association between DTCs in BM and presence of CD8 and CD45RO T cells lymphocytes in BM was not found. At the same time it was shown the association between presence of CD8 and CD45RO T lymphocytes and survival. The presence of CD8- and CD45RO-positive T cells in BM were accompanied with significantly longer overall survival of patients compared to that of patients without CD8- and CD45RO-positive T cells in BM. Conclusion: patients with the presence of CD8- and CD45RO-positive T cells in BM demonstrated better survival of GC patients than those with the absence of these cells in BM. It may be suggested that tumor cells in BM are controlled in a dormant state by T cells in BM, in particular by CD8-positive T cells.

Aim - identification of patient with increased risk of cardiotoxicity would allow not only prevention and early diagnosis of chemotherapy related cardiotoxicity but also administration of optimal dose and duration of chemotherapy. Fiftytwo women with HER2<^>+ breast cancer treated with trastuzumab were included in this study. Patients were prospectively followed with routine cardiac evaluation. Before and after administration of trastuzumab blood samples for NT-proBNP were also taken. The median age was 48,5 year (range: 26 - 74). Hypertension and obesity were two most common comorbidities. The median duration application of trastuzumab was 52 weeks. During median 14,5 (3 - 33) months follow-up cardiac adverse events occurred in 5 (9,6 %) patients and 2 out of 5 was grade III - IV heart failure. Both patients had preserved left ventricular ejection fraction and no symptom of heart failure before trastuzumab but older than 65 years old and had diabetes mellitus and obesity. High level of NT-proBNP (>> 300 ng/ml) was observed in both patients and heart failure recovery was not observed. There was statistically significant difference regarding body mass index (p = 0,004) and diabetes mellitus (p = 0,002) between patients with and without cardiotoxicity. Conclusion: although, cardiac biomarkers still cannot replace routine cardiac monitoring, natriuretic peptides may provide additional tool for detection of patients with high risk of cardiotoxicity and early detection of cardiotoxicity.

Aim - to determine frequency of tumors with immunohistochemical markers of cancer stem cells (CSC) CD44+/CD24- in patients with breast cancer (BC) of different molecular subtype and to evaluate their prognostic value. Object: surgical material of 132 patients with BC stage I - II, age from 23 to 75 years, mean age - 50,2 +- 3,1 years was studied. Methods: clinical, immunohistochemical (expression CD44+/CD24-), morphological, statistical. Results: BC is characterized by heterogeneity of molecular subtypes and expression of markers (CD44+/CD24-). Immunohistochemical study of expression of CSC markers in surgical material has detected their expression in 34 (25,4 %) patients with BC of different molecular subtypes. The highest frequency of cells with expression of CSC marker was observed in patients with basal molecular subtype (44,8 % patients). Most of BC patients with phenotype CD44+/CD24 had stage I of tumor process (34,3 %). Statistical processing of data has showen that Yule colligation coefficient equaled 0,28 (p >> 0,05) that argues poor correlation between stage of tumor process and number of tumors with positive expression of CSC markers. Statistical processing of data has showen high correlation between presence of cells with expression of CSC markers and metastases of BC in regional lymph nodes (Yule colligation coefficient equals 0.943; p << 0,5). Difference in overall survival of patients with BC of basal molecular subtype depending on expression of CSC CD44+/CD24- markers was detected. Survival of patients with basal BC was reliably higher at lack in tumors of cells with CSC markers CD44+/CD24- and, correspondingly, lower at presence of such cells (p << 0,05). In patients with BC of luminal (A and B), HER-2-positive subtypes, significant change in survival of patients depending on expression of CSC markers was not determined (p >> 0,05). Conclusion: significance of tumor cells with markers CD44+/CD24- within the limits of molecular subtype of BC may be additional criterion for advanced biological characteristic of BC, and in patients with BC of basal molecular subtype - for predictive evaluation of individual potential of tumor to aggressive clinical course.

Background: there is paucity of detailed studies of adult T cell acute lymphoblastic leukemia (T-ALL) in developing countries reflecting the condition of these patients including clinical and biological features. This study was carried out to analyze the immunophenotypic characteristics of 40 Moroccan patients with T-ALL and its association with biological and clinical features. Between 2006 and 2009, 130 adult patients diagnosed with acute lymphoblastic leukemia (ALL) were immunophenotyped by 3-color flow cytometry using a panel of monoclonal antibodies. Cases presenting features of a T-lineage phenotype were subjected to detailed analysis including immunophenotypic, clinical and biological parameters. Proportion of T-ALL among ALL Moroccan patients was 31,0 %. Median age of patients was 28 years. Twenty-nine patients were females and 11 were males. 45,0 % of patients (18/40) had features of immature T-ALL stages (pro-T and pre-T ALL), 30,0 % (12/40) of CD1a<^>+ cortical T-ALL stage and 25,0 % (10/40) had a characteristic phenotype of medullary T-ALL. The frequencies of progenitor cell markers CD10, CD34 and TdT expression were 14,0; 57,5 % and 50,0 % respectively. The aberrant expression of B lineage associated antigen CD79a were positive in 20,5 % of the cases and the aberrant expression of myeloid antigens CD13 and/or CD33 was found in 22 (55,0 %) cases. No significant association was encountered between TdT, CD34 or myeloid antigens positivity and high risk features at presentation as age, sex, and white blood cells. I lowever, myeloid antigens (CD13 and/or CD33) was significantly associated with T-cell maturation stages (p = 0,009). Conclusion: to the best of our knowledge, this is the first report from North Africa of immunophenotypic study on adult T-ALL. Our findings indicate that the proportion of T-ALL among ALL in Morocco is similar to that reported in others Mediterranean countries like France and Italy and that myeloid-associated antigens expression is frequently associated with immature immunophenotype.

It is believed that the reason of the leukemic clone cell resistance to treatment with tyrosine kinase inhibitors during chronic myeloid leukemia (CML) is mutations in the genome of an early bone marrow progenitor cells that are CD34-positive. Such cells, regardless of treatment, acquire ability to proliferation and differentiation. This leads to the reexpansion of the CD34<^>+ cells. Aim - to determine the CD34 antigen expression in bone marrow and peripheral blood cells in CML patients with different response to imatinib therapy using the results of hematopoietic cells culturing and the data of flow cytometry. Methods: bone marrow aspirate from 39 patients who were treated with imatinib was studied with cytogenetic, flow cytometry and culture methods in vitro. Inpatients with an optimal response to imatinib therapy the number of colonies was 1,8 times lower than the number of those in the group of patients with a suboptimal response to therapy. In turn, in patients with failure of imatinib therapy the number of colonies was the highest and was 2,1 times higher than the patients with optimal response. The results of cytometric studies have shown that the number of CD34<^>+ cells in bone marrow was significantly higher compared to the number of CD34<^>+ cells in peripheral blood cells and increased with the acquisition of leukemic cells the resistance to imatinib. There was a direct correlation between the number of colonies and clusters in semisolid agar in vitro and the number of CD34<^>+ cells in the bone marrow of patients. Conclusions: The correlation between the number of CD34<^>+ cells and the number of cell aggregates in semisolid agar in vitro indicates the prognostic value of the method for determining CD34<^>+ cells in the patient bone marrow. The parallel increase of their number in the peripheral blood will allow developing express methods for the detection of individual patient response to imatinib therapy.

Background: up to now, the immune status of chronic lymphocytic leukemia (CLL) patients in association with the expression of zeta-chain-associated protein kinase 70 (ZAP-70) in leukemic cells has not been evaluated. Aim: the aim of this work was the study of the peripheral blood (PB) T-lymphocyte phenotypes in ZAP-70-positive (ZAP-70<^>+) and ZAP-70-negative (ZAP-70<^>-) untreated patients witb CLL. Materials and Methods: ZAP-70<^>-, CD25-, CD3-, CD4-, and CD8-positive lymphocytes were enumerated by flow cytometry in PB of 120 untreated CLL patients. CD8+, CD3+CD4+ and CD3+CD25+ cells were counted for the non-leukemic lymphocytes. The patients were distributed into two groups: the ZAP-70<^>+ group of high CLL progression (n = 61), and the ZAP-70<^>- group of low CLL progression (n = 59). In the ZAP-70<^>+ group, the ratio CD4/CD8 (0,33 +- 0,62; p = 0,001) and the numbers of the CD3+ (34,8 +- 8,1 %; p = 0,01), CD3+CD4+ (24,4 % +- 4,8; p = 0,001), and CD3+CD25+ (6,2 +- 0,91 %; p = 0,001) lymphocytes were reduced and the percentage of the CD8+ cells (73,1 +- 4,6 %; p = 0,0001) was above the norm. In the ZAP-70<^>- group, the number of the CD3+CD4+ cells (36,9 +- 6,1 %; p = 0,001) was witbin the norm, but the numbers of the CD8+ (11,3 +- 1,1 %; p = 0,0001) and CD3+ (41,2 +- 5,3 %; p = 0,05) lymphocytes were reduced; the ratio CD4/CD8 (3,26 +- 0,88; p = 0,001) and the percentage of the CD3+CD25+cells (27,1 +- 3,4 %; p = 0,0001) were above tbe norm. Conclusions: our data show that the increased CD4/CD8 ratio, caused by tbe reduced number of the CD8+ lymphocytes, and the increased numher of CD3+CD25+ cells are characteristic for the ZAP-70<^>- group (slow progressing) of untreated CLL, patients. In ZAP-70<^>+ patients, the CD4/CD8 ratio was significantly below the norm indicating an active disease process. Results of study contribute to identification of CLL patients with different prognosis in routine diagnostic/prognostic procedures.

Aim - the expression differences of SCN8A (which encodes type VIII alpha subunit of voltage gated sodium channel) and NDUFC2 (which encodes C2 subunit of Complex I enzyme moxidative phosphorylation) genes were evaluated in paired colorectal cancer (CRC) tissues which was relied on our partial transcriptome analysis data in cancer cell lines. A total of 62 paired tissues of CRC patients (34 male, 28 female) were included in the study. The mRNA levels of SCN8A and NDUFC2 genes were determined by using real-time PCR (qRT-PCR and semiquantitative PCR). SCN8A gene expression level was significantly lower in tumor tissues (p = 0,0128) and in the patients with tbe age below 45 years (p = 0,0049). There were also meaningful relationships between the gender, grade of CRC, tumor location, histopatbological classification, and SCN8A expression. There was no NDUFC2 differential expression. However, the tumors taken from rigbt colon had significantly lower NDUFC2 expression. Conclusion: although the voltage gated sodium channels (VGSCs) and Complex I (Cl) were associated to a number of diseases including different types of cancers, tbe different subunits of Cl and individual members of VGSCs seem to be cancer type-specific in varying proportions.

Symptomatology of oncological diseases consists not only of local symptoms caused by the primary malignancy or its metastases, but also by general systemic signs that are not directly connected with the tumor. These symptoms are mostly associated with auto-immunity or endocrine influences. In many cases, the source of paraneoplastic syndromes (PNS) is unknown. Nearly 15 % of on-cological patients demonstrate these syndromes but it is diagnosed much more rarely. The survey of the numerous PNS is offered. The significance of the PNS differs for oncologists and other physicians who encounter it m their practice. The reason of those differences, as well as the connection between PNS and cancer toxicity is discussed. The experience of antitoxic therapy (hemosorption, lymphosorption, enterosorption) used in our clinic in the previous years is overviewed.

Exposure to ionizing radiation is associated with increasing risk of various types of hematological malignancies. The results of major studies on association of leukemias and radiation exposure of large populations in Japan and in Ukraine are analyzed. The patterns of different types of leukemia in 295 Chernobyl clean-up workers diagnosed according to the criteria of up-to-date World Health Organization classification within 10 - 25 years following Chernobyl catastrophe are summarized. In fact, a broad spectrum of radiation-related hematological malignancies has been revealed both in Life Span Study in Japan and in study of Chernobyl clean-up workers in Ukraine. The importance of the precise diagnosis of tumors of hematopoietic and lymphoid tissues according to up-to-date classifications for elucidating the role of radiation as a causative factor of leukemias is emphasized. Such studies are of high importance since according to the recent findings, radiation-associated excess risks of several types of leukemias seem to persist throughout the follow-up period up to 55 years after the radiation exposure.

Aim - in this study, we evaluated the carcinostatic effects of combined ascorbic acid (AsA) and a capacitive-resistive electric transfer (CRet) hyperthermic apparatus-induced hyperthermic treatment on Ehrlich ascites tumor (EAT) cells. EAT cells were exposed to various AsA (0 - 10 mM) concentrations for 1 h; they subsequently underwent CRet treatment for 15 min at <$E42 symbol Р roman C>. Cell viability was assessed by the WST-8 assay 24 h alter the combined treatment. Reactive oxygen species involvement was evaluated using catalase and tempol; caspase-3/7 activation was determined by their fluorescent substrates; cell proliferation were estimated by time-lapse observation. The effect on the cell cycle was analyzed by flow cytometry. Combined AsA and CRet treatment syncrgistically suppressed cell viability compared with either treatment alone, and these synergistically carcinostatic effects were evident even at noncytotoxic concentrations of AsA alone (<$Esymbol Г~2> mM). The carcinostatic effects of combined AsA and CRet treatment were attenuated in a dose-dependent manner by catalase addition, but not by the superoxide anion radical scavenger tempol. Time-lapse observation revealed that combined AsA and CRet treatment activated caspase-3/7 at 10 - 24 h after treatment, accompanied by significant cell growth suppression. Cell cycle analysis revealed that the rate of sub-G 1-phase (apoptotic) cells was drastically increased at 12 h and 24 h, and that the G2/M-phase cells gradually increased at 6 - 24 h after treatment. Conclusion: these results indicate that combined AsA and CRet treatment synergistically inhibits EAT cell growth through G2/M arrest and apoptosis induction via H2O2 generation at lower AsA concentrations; this carcinostatic effect cannot be exerted by AsA alone.

In recent years gold nanoparticles (AuNPs) have received considerable attention for various biomedical applications including diagnostics and targeted drug delivery. However, more research is still needed to characterize such aspects of their use in clinical oncology as permeability, retention and functional effect on tumor cells. Aims - this study was designed to describe the effect of non-functionalized AuNPs on LNCaP prostate cancer cells growth. Material and Methods: LNCaP cells were cultured in RPMI-1640 medium containing AuNPs covered by polyvinylpyrrolidone of average size 26,4 nm (10,0 mu g/ml). Counts of cells were calculated and their morphology was examined. Results: AuNPs conglomerates have been visualized in cultured cells. After 4-day incubation in presence of AuNPs significant retardation of LNCaP cells growth was observed both in 5 alpha-dihydro testosterone stimulated and non-stimulated cultures. No morphological changes of live LNCaP cells were seen in any experiment. Conclusion: given absence of morphological changes in live cells and dribble and relatively constant numbers of dead cells, it was concluded that inhibitory effect of AuNPs on LNCaP cells growth was caused by alterations of proliferation.