The role of microRNAs in endometrial cancer and influence on future therapy: focusing on miRNA-21.

MicroRNAs are small noncoding polynucleotides, which are involved in numerous biological processes including cell proliferation, differentiation, embryonic development, as well as regulation of cell death and survival. Recent investigations have shown impact of microRNAs on cancers prognosis and diagnosis. Current review focused on the role of microRNA-21 in cancers tumorigenesis. Endometrial cancer is the most common gynecological malignancy and the fourth most common in general classification of cancers in Western Europe; thus discovering new molecules may become a useful diagnostic tool. Furthermore, in this review, the authors emphasized microRNAs having considerable influence on endometrial cancer development. Finally, they highlighted the role of microRNAs as a target for future therapy and circulating microRNAs as a potential biomarker in malignancies.

Study of the genotoxic potential of iron ions by the SOS chromotest.

Modulation of iron ions induced SOS response by scavengers of reactive oxygen species was studied in SOS chromotest in three strains of Escherichia coli (PQ37, PQ300 and OG400). Iron ions in the absence of reductants induced SOS response generated by reactive oxygen species in a dose dependent manner and this was inhibited in the presence of catalase.

Effects of iron and copper ions on the inducibility of hydrogen peroxide in E. coli.

Inducing capacities of hydrogen peroxide in SOS chromotest were investigated in the absence and in the presence of iron and copper ions. Strain PQ37 of Escherichia coli and two strains with altered protection against oxidative damage (PQ300 and OG400) were employed. The latter two strains were more sensitive to the hydrogen peroxide inducing activity than strain PQ37. At the concentration of 150 nmol/ml and 300 nmol/ml, iron ions induced SOS response. At the concentration range from 30 nmol/ml to 300 nmol/ml iron enhanced the effects produced by H2O2. Results with copper were negative.

Influence of ascorbic acid on cytotoxic activity of copper and iron ions in vitro.

We investigated survival of two kinds of human embryonic cells (CLV102, Lu106) and human melanoma cells (Mel8) exposed to exogenous iron and copper ions in the absence or in the presence of ascorbic acid, catalase and superoxide dismutase. Iron ions produced cytotoxicity towards both kinds of cells dependent on its concentration. Catalase suppressed the cytotoxicity induced by iron ions in Lu106 cells. whereas in CLV102 and Mel8 cells, was ineffective. By contrast, superoxide dismutase abolished the cytotoxicity of iron ions towards CLV102 cells, whereas in Lu106 and Mel8 cells, was ineffective. The mixture of iron ions with ascorbic acid was less cytotoxic than iron ions themselves or ascorbic acid itself, only in CLV102 and Lu106 cells. Ascorbic acid enhanced drastically cytotoxic effect of copper ions in all kinds of cells.

Studies on the nature of cytotoxic effects induced by dihydralazine.

The effects of scavengers on the cytotoxicity of dihydralazine were evaluated. Pretreatment of two kinds of mammalian cells cultured in vitro with catalase or sodium dismutase abolished partially or almost totally the effects of the drug. Hydroxyl radicals scavengers dimethylsulphoxide and D-mannitol minimized the cytotoxic response of both kinds of cells.

Studies on the nature of genotoxic and cytotoxic effects induced by hydralazine.

The nature of genotoxic and cytotoxic effects induced by hydralazine was analyzed taking into account possible protection of cells by catalase, superoxide dismutase and dimethyl sulfoxide. For the experiments designed to evaluate the influence of scavengers on the genotoxicity expressed as the SOS induction factor the E. coli PQ37 strain was used. The cytotoxic effects were investigated in V3 cells cultured in vitro. The genotoxicity and cytotoxicity of hydralazine were suppressed by catalase in a dose-dependent manner but they were enhanced by superoxide dismutase. No protective effect of dimethyl sulfoxide was observed. Our results indicate that H2O2 plays an essential role in the genotoxicity and cytotoxicity of hydralazine.

Comparison of the induction of SOS repair in Escherichia coli PQ37 and PQ243 by antineoplastic agents.

Six alkylating antineoplastic drugs (Cyclophosphamide, Chlorambacil, Busulfan, Melphalan. Streptozotocin and Lomustine) and two reference compounds (methyl methanesulphonate and N-methyl-N'-nitro-N-nitrosoguanidine) were investigated in the SOS Chromotest using the Escherichia coli strain PQ37 (wilde-type) and derived strain (PQ243), which carries the same markers as PQ37 and additionally tagA alkA. As a measure of the SOS induced activity induction factors of sflA::lacZ expression were determined. The strain PQ243 was more sensitive towards all compounds inducing SOS DNA repair then the strain PQ37 Cyclophosphamide was detected as negative in the strain PQ243 in the presence of an exogenous metabolic activation system. Lomustine was inactive both in the mutant strain and in the wild-type strain in the presence of S9 mix fraction as well as in the absence of it. Melphalan and Busulfan (without or with S9 mix) were shown to be positive exclusively in the strain PQ243. Based on these results, we discuss the usefulness of the strain PQ243 in the monitoring of the genotoxicity of drugs and in the genetic analysis of their mode of action.

Characteristics of mutagenesis by bleomycin and adriamycin in salmonella typhimurium: action of superoxide dismutase.

The role of reactive oxygen species in adriamycin and bleomycin-induced mutagenicity was investigated in Salmonella typhimurium TA98 and TA102 respectively. Activity of superoxide dismutase (SOD) was inhibited by preincubation of bacteria with diethyldithiocarbamate (DEDTC). Results of Ames test may suggest the involvement of active oxygen species in bleomycin induced mutagenesis and an absence of their participation in adriamycin induced mutagenesis.

Studies on the mechanism of hydralazine induced mutagenicity and genotoxicity.

The mutagenicity (Ames test) and genotoxicity (SOS Chromotest) of hydralazine were studied. Hydralazine was found to be genotoxic to E.coli PQ37. In experiments with E.coli MD332 it was genotoxic in responsive temperature (30 degrees C) but not genotoxic in non-responsive temperature (42 degrees C). Hydralazine was mutagenic to S.typhimurium TA100 and TA104 but not mutagenic to TA102. Different active oxygen species scavengers did not influence the genotoxicity and mutagenicity of hydralazine.

Genetic effects of binazine and hydralazine in vitro and in vivo.

The mutagenic and genotoxic activities of binazine and hydralazine were studied. In the Ames test, both with and without S-9 fraction, hydralazine was mutagenic in strains Salmonella typhimurium TA100 and TA1537, whereas binazine was not mutagenic in these strains. Both drugs were negative in mice micronucleus test.

Studies on the mechanism of mutagenicity and genotoxicity induced by dihydralazine.

Dihydralazine was found to be mutagenic towards S. typhimurium TA1537, TA97, TA1538 and TA98 and genotoxic towards E. coli PQ37. Using the nitro blue tetrazolium reduction method we have found that dihydralazine can generate active oxygen species. The possible role of active oxygen species in mutagenicity (Ames test) and genotoxicity (SOS Chromotest) of dihydralazine was studied by testing the influence of the different active oxygen species scavengers on these two processes. Of the active oxygen scavengers tested, only superoxide dismutase suppressed partially the mutagenic and genotoxic activity of dihydralazine. This result seems to indicate that superoxide anion play a role in these two biological events.

Metastases of ovarian endometrioid carcinoma to fibrothecomas of both ovaries.

A case is described of a 61-year-old woman who suffered from ovarian endometrioid carcinoma with the secondaries in fibrothecomas of both ovaries. Such target of metastases is really uncommon.

Evaluation of the SOS chromotest for detection of genotoxic drugs.

In the present investigation, the SOS Chromotest with E. coli PQ37 was evaluated. The potential of the test to identify genotoxic properties of different cytostatics was examined. Only intercalating agents showed good activity. The SOS Chromotest appeared to be less effective than the Salmonella mutagenicity test in the detection of alkylating agents.

Evaluation of mutagenic, genotoxic and transforming properties of Ukrain.

Evaluation of mutagenic and genotoxic properties of Ukrain was on the basis of the Ames and micronucleus tests. Ukrain was investigated for its ability to induce morphological transformation of embryonic cells of the Syrian hamster. Under the experimental condition used in this study, Ukrain was found to be non-mutagenic and non-genotoxic, and furthermore did not induce morphological cell transformation.

An evaluation of antimutagenic properties of vitamin E.

The influence of vitamin E on the mutagenic activities of aflatoxin and adriamycin was studied. The results indicate that vitamin E shows antimutagenic activity towards aflatoxin B1 only when homogenized with liver tissue.

[Combination of gentamycin and amikacin with rifampicin, ethambutol and isoniazid on selected standard strains of Mycobacterium species in experiments done in vitro and in vivo]. / Skojarzone dzialanie gentamycyny i amikacyny z ryfampicyna etambutolem i hydrazydem kwasu izonikotynowego na dobrane szczepy wzorcowe z rodzaju Mycobacterium w doswiadczeniach in vitro i in vivo.

The authors present results of in-vivo and in-vitro studies of combined effect of gentamycin , amikacin and rifampicin , ethambutol, isoniazide on selected standard strains of Mycobacterium sp. (Myc. H37Rv, Myc. An5, Myc. wells, Myc. kirchberg, Myc. kansasii, Myc. intracellulare, and Myc. fortuitum). In in-vitro studies the synergistic effect of gentamycin and amikacin with the tuberculostatic drugs was demonstrable on all Mycobacterium strains. The weakest effect was seen on Myc. fortuitum colonies. In-vivo studies have also shown this synergistic effect on all studied strains, and a much weaker effect when used in monotherapy. The authors have shown the possibility of using combination of gentamycin and amikacin with RMP, EMB, INH in treating Myc. intracellulare infections.