Chromosomal abnormalities of bone marrow cells in dynamic chronic myeloid leukemia (CML) with bcr-abl-tyrosinkinase inhibitor (400 mg/m2) in 34 children and adolescent were estimated. Appearence of additional chromosomal abnormalities such as del(16)(q22), del(11)(q23), del(6) (q23), del(21)(q12), trisomy chromosome 8, additional neartetraploid clones were evidence about tumor cells resistence to therapy in children and adolescent.

The treatment of malignant tumors may cause severe adverse reactions including cardiovascular problems. The case of a young woman with trastuzumab (Herceptin) induced dilatation cardiomyopathy with favorable outcome is presented in the article.

A decision regarding adjuvant chemotherapy in early (operable) breast cancer in the past was made entirely on the basis of clinical and pathological features. However with the growing awareness of tumor biology and the possibility of the genomic analysis to determine the molecular subtypes of breast cancer it is getting real to identify patients whose tumors are resistant to chemotherapy or vice versa benefit from its addition. Despite the fact that genomic analysis allows some patients avoiding chemotherapy (especially patients with localized breast cancer), such studies do not indicate the most appropriate chemotherapy regimens. Therefore treatment decisions should be based on a combination of biological features of the tumor, its stage and signs that characterize the patient such as age and tolerance to the side effects of therapy.

Antifibrinolytic drug epsilon-aminocaproic acid as a therapeutic form (5% solution in saline) was tested for antitumor activity in the autochthonous subcutaneous tumors of mice, induced by benzo (a) pyrene, in monotherapy mode (instead animals received drinking water) and in combination with cyclophosphamide, which was administered once intraperitoneally in the dose of 200 mg/kg. In the control groups, treated with drinking water and saline solution instead of water, there was no stabilization and reduction in tumor volume, while in the groups receiving epsilon-aminocaproic acid, cyclophosphamide and their combination statistically significantly in comparison with the control groups there was increased the proportion of tumors with not changed or reduced volume; epsilon-aminocaproic acid enhanced the antitumor effect of cyclophosphamide. The data obtained are for further study of the antitumor effect of epsilon-aminocaproic acid.

Hepatocellular carcinoma (HCC) is one of the most common neoplasms worldwide. Hepatocarcinogenesis is associated with deregulation of the cell signaling thus targeted therapy can decelerate HCC progression by specific inhibition of alternated signaling cascades. Sorafenib is the only multitarget drug approved for HCC treatment that blocks several crucial oncogenic signaling pathways thus suppressing tumor growth, metastasis and providing survival benefit for subset of patients sensitive to sorafenib. Compensatory activation of other tumorigenic mechanisms may lead to decrease of HCC sensitivity to sorafenib. HCC are heterogenic tumors of epithelial origin, and presence of low-differentiated subpopulations of cancer stem cells or dedifferentiated fibroblastoid cells, that are less sensitive to sorafenib due to resistance to growth-inhibitory action of the drug, promotes HCC resistance to sorafenib. Analysis of the expression profile of genes encoding tissue-specific proteins, components of cell junctions, stem cell and mesenchymal markers can reveal sorafenib-resistant populations in HCC and identify signaling pathways that reduce response to sorafenib. Identification of individual sorafenib resistance mechanisms may be useful for rational choice of an appropriate combination of targeted drugs for retardation of HCC progression and improving the efficacy of therapy

We have studied dose- and time-dependent antitumor and cytotoxic effects of Erwinia carotovora L-asparaginase (ECAR LANS) and Escherichia coli L-asparaginase (MEDAC) on human leukemic cells and human and animal solid tumor cells. We determined the sensitivity of tumor cells to L-asparaginases, as well the effect L-asparaginases on cell growth rate, protein and DNA synthesis per se and with addition of different cytostatics. The data obtained demonstrated that ECAR LANS L-asparaginase suppressed growth of all tested solid tumor cells. Evaluation of leukemic cell number after treatment with L-asparaginases for 24, 48 and 72 h demonstrated that asparagine deficiency did not kill cells but stopped normal cell division and had no effect on protein and DNA synthesis. Cytofluorometric study of solid and leukemic cells demonstrated that the treatment with L-asparaginase for 72 h did not change cell cycle phase distribution and did not increase the number of apoptotic cells. The HL-60 cell line was only exemption. At the same time, cells treatment with L-asparaginase and doxorubicin combination leaded to increase of apoptotypical cell number to 60% for MCF7 cells, to 40% for Jurkat cells and to 99% for HL-60 cells. We have excluded apoptosis as main reason for tumor cell death after asparaginase treatment because multi resistant Jurkat/A4 cells have been asparaginase sensitive. We have not found ECAR LANS L-asparaginase effect on normal human fibroblasts growth ability and we had come to conclusion that enzyme cytotoxcisity related only with asparagine deficiency.

The effect of a low uptake dose of oregano essential oil with drinking water for three months (Origanum vulgare L.) on the degree of Lewis carcinoma engraftment and some parameters of oxidative stress has been studied in vivo using F1 DBA C57 Black hybrid mice. Oregano essential oil has been established to possess an anticancer activity. The degree of tumor engraftment decreased by 1.8 times, its size decreased by 1.5 times, and the development of tumor was significantly suppressed in sick mice under the effect of oregano essential oil. It was found that the uptake of essential oil did not affect the intensity of lipid peroxidation in the brain of mice and resulted in a significantly (by 36%) decreased content of secondary lipid oxidation products in the liver as shown in a reaction with thiobarbituric acid as compared to control subjects. The activity of antioxidant enzymes was found to increase after three months of essential oil uptake (by 1.5-3 times) as compared to the control group. This effect of essential oil supports the presence of bioantioxidant properties in this essential oil.

N6-derivatives of N12-ribosyl-indolo[2,3-a]pirrolo[3,4-c]carbazole-5,7-dione are synthesized as potential antitumor agents, in which an atom of N6-pyrrole part of heterocycle is included into the dipeptide residual of the general formula >N6-(CH2)n-CO-Ala/βAla-OMe (n = 2 or 3). These compounds are derived by reacting of 13-methyl-12-(2,3,4-three-O-acetyl-β-D-ribopyranosyl)indolo[2,3-a]furano[3,4-c] carbazole-5,7-dione with dipeptides, having an unreplaced N-amino end-group, in DMF at 130°C, wherein the nitrogen atom of peptide amino group replaces oxygen O6 in furan ring of heterocycle and is embedded in imide nitrogen atom of pyrrole N6. The ability of the obtained compounds to inhibit growth of SKOV3 human ovarian carcinoma cells was studied, only derivative with radical >N6-(CH2)3-CO-L-Ala-OMe showed cytotoxic activity with an inhibitory concentration of IC50 = 8 μM.

Methyl methanesulfonate (MMS) is an alkylating agent commonly used in models of genotoxic stress. It methylates bases in DNA but also leads to oxidative stress. The transcription factor Rpn4 protects yeast cells from toxic effect of MMS. Although Rpn4 is a major regulator of ubiquitin-proteasome system (UPS), a number of data points to its participation in the stress response regardless of the UPS. We have demonstrated that under the methyl methanesulfonate stress Rpn4 promotes the regulation of several genes involved in DNA repair, antioxidant response and glucose metabolism. We suggest a mechanism of complex action of Rpn4 in the stress response.

Among means of alternative and complementary therapy for cancer, acupuncture holds a special place. This is because, unlike the most other methods of alternative and complementary therapy for cancer, efficacy and safety of acupuncture in the symptomatic treatment for cancer patients is considered as proven. Not accidentally such leading cancer centers in the USA as the Dana-Farber Cancer Institute in Boston, the Memorial Sloan-Kettering Cancer Center in New York, the M.D.Anderson Cancer Center in Houston integrated acupuncture in accepted in these centers treatment standards and are staffed by licensed professionals on acupuncture. Particular attention is drawn to the use of acupuncture in hospices. It is stressed that it is the most effective and safe in the performance by qualified licensed professionals

To evaluate the efficiency and safety of monotherapy with bendamustine (B) and therapy with B in combination with rituximab (B + R) in patients with chronic lymphocytic leukemia (CLL) accompanied by renal failure (RF).

The fluorescence intensity of acridine orange (AO) dye bound to living human leukocytes, rat leukocytes, and Pliss lymphosarcoma cells of rat has been studied by fluorescence microscopy. The cell suspension of each test was divided into two parts, to one of which the drug cisplatin was added to a final concentration of 0.1 μg/mL and the mixture was incubated for 20 - 60 min. Acridine orange was then added and the average intensity of red and green fluorescence of cells was determined. The brightness of AO in the green region of the spectrum was reduced approximately 3-fold (p = 0.001) in cells with cisplatin. In the red region of the fluorescence, differences in the brightness of cells with and without cisplatin were not observed. These data indicate that a decrease in the brightness of green fluorescence of AO can be a test for the presence of cisplatin in cells.

To study clinical presentations and neuroimaging results in post chemotherapy encephalopathy.

In this study, we investigated how the protein YB-1 influenced on the expression of genes coding ABC transporters and on drug resistance in several cell lines, in which originally gene MDR1, coding P-glycoprotein, was not expressed. These populations were significantly different in the presence of mRNA YB-1 and the nature of the intracellular localization of the protein YB-1. However incubation of cells in all studied populations in the culture medium with serum after starvation led to translocation of YB-1 in the cell nucleus. The increase of the number of cells with nuclear localization of YB-1 correlated with increased amount of mRNA YB-1. Processing of cells with drug LY-294,002 by PI3K/Akt inhibitor prevented the translocation of the protein YB-1 into the nuclei of cells, and the cells became more sensitive to the toxic action. Thus, we observed that the signaling pathways involved in control of cell proliferation, in particular a signaling cascade PI3K/Akt were involved in the control of the intracellular localization of YB-1 in cell populations of ovarian cancer, melanoma and human prostate cancer. In these cells the nuclear localization of YB-1 correlated with an expression of MDR and MRP1 DCRP genes and with a sensitivity of cells to a number of drugs.

In experimental animals with tumors it was studied antitumor activity of spirocyclic hydroxamic acids which could be classified as targeted agents as their target was enzyme histonedeacetylase, which was involved in the neoplastic process. The results showed that the hydroxamic acids were chemosensitizers for anticancer agents increasing their efficacy and enabling the researchers to reduce significantly the therapeutic dose. Also it was showed that hydroxamic acid, containing nitrogen mustard, was effective in the action on tumors with phenotype and genotype of multidrug resistance.

The cytostatic/cytotoxic effects of the maleimide derivative 1-(4-Cl-Benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrol-2,5-dione (MI-1) have been estimated on epithelial derived human cell cultures (Colo 205, MCF-7, and Hela). The anticancer and toxic effects of MI-1 have been investigated on DMH-induced cancer development and normal colon morphology in rats. The results showed that the compound studied has low cytotoxicity but produces a strong antiproliferative effect on cell cultures and partially suppresses colon cancer development in DMH-induced model. The MI-1 effect on normal colon mucosa is insignificant, and no destructive changes have been detected in the intestine of rats. This maleimide derivate can be considered as a promising anticancer drug.

The paper describes a case of a patient with refractory hairy cell leukemia. In spite of the absence of CD25 expression, the disease was classified as a classical form according to the WHO classification (2008), as also confirmed by the detection of BRAFV600E mutation. The disease was characterized by resistance to all lines of therapy (interferon-a, splenectomy, cladribin). Clinical and hematological remission was achieved within 2 months of administration of the BRAF kinase inhibitor vemurafenib.