The results of conservative treatment of 121 patients with endometrial atypical hyperplasia (EAH) and early endometrial cancer (EC) with preservation of fertility are presented. In EAH (n = 56) for 6 months the intrauterine spiral Mirena was used. The effectiveness was 91%, the recurrence rate 16%, pregnancies occurred in 16% of patients. In EC (n = 65) hormone therapy was conducted for 6 months using the intrauterine spiral Mirena and zoladex. The effectiveness was 79%, recurrence rate 22%, pregnancies occurred in 24% of patients. Based on our data and on the results of other studies, the benefits and risks of hormone therapy alone for EAH and EC are discussed in women of reproductive age.

Ovarian cancer is one of the most aggressive malignant tumors in women. The role of hormone therapy in the treatment for ovarian cancer is not fully studied up to now. The literature contains data on the efficacy and safety of treatment with antiestrogens and aromatase inhibitors for recurrent ovarian cancer. The article summarizes the epidemiology, preclinical and clinical studies related to the role of estrogen and aromatase expression in this disease as well as the role of aromatase inhibitors in the treatment for ovarian cancer.

Simultaneously with keeping one of the leading positions in the structure of oncogynecological morbidity, endometrial cancer (EC) presents for many decades 'the food for brains' of cancer endocrinologists. Step by step development of contemporary ideas and collecting the data on mechanisms of hormonal carcinogenesis, the role of excessive estrogenic stimulation and metabolic syndrome/insulin resistance as risk factors for EC, very probable gradual changing of the disease phenotype and significance of genetic damages (with PTEN-mutations as one of the examples), as a consequence point at potential perspectives in the usage of preventive and therapeutic approaches in this important area.

The main goal of this work was to study the intracellular signaling pathways responsible for the development of hormone resistance and maintaining the autonomous growth of breast cancer cells. In particular, the role of PAK1 (p21-activated kinase 1), the key mitogenic signaling protein, in the development of cell resistance to estrogens was analyzed. In vitro studies were performed on cultured breast cancer cell lines: estrogen-dependent estrogen receptor (ER)-positive MCF-7 cells and estrogen-resistant ER-negative HBL-100 cells. We found that the resistant HBL-100 cells were characterized by a higher level of PAK1 and demonstrated PAK1 involvement in the maintaining of estrogen-independent cell growth. We have also shown PAK1 ability to up-regulate Snail1, one of the epithelial-mesenchymal transition proteins, and obtained experimental evidence for Snail1 importance in the regulation of cell proliferation. In general, the results obtained in this study demonstrate involvement of PAK1 and Snail1 in the formation of estrogen-independent phenotype of breast cancer cells showing the potential role of both proteins as markers of hormone resistance of breast tumors.

In Wistar rats with transplanted Walker 256 carcinosarcoma a use of melatonin as monoagent causes changes in intracellular organization of endothelial cells: reduced volume density of mitochondria, granular cytoplasmic network, micropinocytic vesicles, reduced the number density of free and attached ribosomes, which leads to increased apoptosis of tumor cells of Walker 256 carcinosarcoma.

The study of antitumor efficacy of dioxadet in chemoperfusion treatment of ascitic ovarian cancer was carried out in 125 Wistar female rats. Ovarian cancer was inoculated intraperitoneally at a number 1x10(7) tumor cells per rat. Intraperitoneal administration of dioxadet as well as chemoperfusion was performed once in 48 hours after the ovarian cancer inoculation. Dioxadet was used at maximal tolerated doses which were 1.5 mg/kg for intraperitoneal administration, 30 mg/kg for normothermic intraperitoneal chemoperfusion (IPEC), and 15 mg/kg for hyperthermic intraperitoneal chemoperfusion (HIPEC). Antitumor effects of dioxadet were estimated in increase of median survival. In the control group, where animals didn't receive any treatment, the median survival was 9 days. Increase of the median survival after intraperitoneal administration of dioxadet, IPEC and HIPEC with dioxadet was 211% (p=0,001), 244% (p=0,001) and 444% (p=0,001), respectively, compared to the control group. Hence, intraperitoneal chemoperfusion with dioxadet (normo- or hyperthermic) is more effective compared to standard intraperitoneal administration of the drug. At HIPEC with dioxadet potentiating antitumor action of hyperthermia and dioxadet on the ovarian cancer growth was achieved.

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.

The article presents examination results of 26 patients with macular edema (ME) due to retinal vein occlusion (RVO) before and 1 month after an intravitreal injection of ranibizumab (Lucentis). Besides routine assessment, retinal spectral-domain optical coherent tomography (OCT) was performed in all cases. In accordance with derived OCT patterns of macular edema the patients were devided into two groups: swelling of the inner and outer retinal layers with serous detachment of neuroepithelium (group 1) and intraretinal edema with pseudocysts (group 2). It is shown that initial OCT features of retina in patients with ME due to RVO are prognostic for treatment results (serous retinal detachment may serve as a preventing factor of photoreceptor damage) and that visual improvement in patients with ME and serous detachment of neuroepithelium anticipates morphological changes.

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.

On the basis of betulinic and oleanolic acids triterpenoids with different with different amine fragments: (3-aminopropoxy)-, 3-acetyl-(3-aminopropyl)amino-, 6-[bis(3-aminopropyl)amino]hexylamino-, (3-aminopropyl)-4-aminosulfonyl-4-phenylamino- at positions C3 and C28 were synthesized. It is shown that betulonic acid amide with 4,4'-diaminodiphenylsulfonic substituent don't render antitumor effect in mice with transplantable Lewis lung carcinoma, but possess significant anti-inflammatory activity.

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.

Metastasis to the lung is the most common place connected with kidney cancer progression. Wherein metastasectomy is accompanied by satisfactory 5- and 10-year survival achieving 49% and 21% respectively. Pleural lesion due to this tumor develops as a part of systemic metastasis and, as a rule, is a consequence of neoplastic spread from lung parenchyma, which indicates a poor prognosis and is an indication for palliative care.