The study is concerned with the effects of non-specific blocking gap junction communication with oleamide as well as genesis and spreading of melanoma B16 metastases to the lung in mice C57B1. The blocking exerted no distinct influence on primary tumorigenesis but had a marked effect on metastatic spread. Oleamide treatment during tumor growth led to an increase in area covered by metastases. A correlation was established between metastatic frequency and dosage: 1 mg/kg was followed by an upsurge in frequency of secondary lung tumors while 10 mg/kg--by a drop.

Effects of a new synthetic progesterone derivative 17a-acetoxy-3b-butanoyloxy-6-methyl-pregna-4,6-dien-20-one (ABMP) and the reference gestagen preparations on the rat thymus were evaluated by the degree of variation of the intracellular levels of calcium and cAMP, 3H-uridine inclusion into RNA, thymocyte viability, and thymus mass. It is shown that gestagens can produce antiglucocorticoid action on thymocytes, this activity being most pronounced in the case of ABMP.

To characterize cytarabine effects on human endothelium expression of cell adhesion molecules (CAM) of various classes and interaction of cultured endothelial cells (EC) with blood leukocytes.

Neurotrophins are structurally related growth polypeptide factors that play an essential role in the development and functioning of the vertebrate nervous system. They provide forming and survival of different neuron populations of the central and peripheral nervous system. Neurotrophins are also involved in the processes of higher nervous activity. Neurotrophins are active not only in the nervous system; these universal trophic factors are important for the development, proliferation, and maintaining of different tissues including tumor tissues. Changes in the neurotrophin signaling system are significant for the pathogenesis of malignancies at the initiation stage as well as during the tumor progression. Neurotrophins and their receptors are complex multi-component system controlled in a very complicated manner. This system can affect the cells and tissues in different ways; the final results of neurotrophin action vary from cell maintenance and survival to apoptosis. Differences in mechanisms and results of the neurotrophin action depend on the cell and tissue type in which the system works. The effects of the neurotrophin signaling are especially variable in different malignancies. In the review we summarize the information on the neurotrophin signaling in various tumors and demonstrate its contribution to the disease course.

Tamsulone-FS--a novel Russian alpha1A/D-adrenoblocker (Farm-Syntez)--was studied in a randomized multicenter comparative trial in patients with prostatic adenoma. Pilot results agreed with other trials published in the literature and demonstrated tamsulone-FS efficacy and safety for management of lower urinary tract symptoms caused by prostatic adenoma. The efficacy and safety of tamsulone-FS was comparable to those of omnik. This drug can be recommended for wide clinical practice in prostatic adenoma. It is registered by Roszdravnadzor (certificate N LC-000859 of 03.11.2005) and allowed for production and sale.

Mechanisms of myelotoxic action of Doxorubicin associated with changes in NAD(+)-glycohydrolase/CD38 expression and activity have been assessed. During the acute and subacute exposure of bone marrow cells to Doxorubicin in vivo, expression of CD38 is decreased corresponding to elevation of intracellular and extracellular NAD+ concentrations. These changes are associated with increased susceptibility of hemopoietic cells to the apoptogenic action of Doxorubicin. Possible role of NAD(+)-glycohydrolase/CD38 in the regulation of sensitivity of the cells to the cytotoxic effects of the xenobiotic is discussed.

Mechanisms of action of pantogematogen (PG), granulocyte colony-stimulating factor (G-CSF), glycyram, and D-glucuronic asid (D-GA) have been investigated under the conditions of myelosuppression caused by the introduction of cyclophosphane. It is established that the activation of granulocytopoiesis by these preparations is based on various mechanisms: G-CSF directly stimulates the proliferation and differentiation of hemopoietic cells; PG enhances the proliferation of granulocytes due to activation of the regulatory systems; D-GA and glycyram normalize the structural and functional organization of a bone marrow, thus providing intensive maturing of the colony-forming units.

The present paper proposes to employ the cultured tumor cells of the breast and chick fibroblasts after long-term cultivation (for above 24 days) to determine their individual drug sensitivity and, as a criterion of cell damage, to use the percent of destruction of the cell layer formed in the wells 24 hours after drug insertion. It also presents the comparative results of tests of 2 cellular models that have been used to determine the in vitro sensitivity of the cells of breast cancer and chick fibroblasts to melfalan and its complex compound with copper acetylacetonate - MOK*M. At the same time, the cytotoxic activity of MOK*M and melfalan against tumor cells has been not shown to differ greatly (16.02+/-1.85 and 15.71+/-0.65% cell layer destruction, respectively), but the same activity of MOK*M against the model of intact cells (chick fibroblasts) was much less (15.23+/-1.97%) than that of melfalan (95.39+/-1.11%). The test system proposed by the authors is of certain informative value and it may be used for the determination of the individual sensitivity of tumor cells to antitumor drugs.

The development of resistance of K562 human erythroleukemia cells to doxorubicin, a widely used antitumor antibiotic with the prooxidant action, leads to changes in the free-radical state of cells. It has been found that the formation of superoxide anion in resistant cells decreases. The introduction of doxorubicin to the culture medium induced a considerably lesser increase in the formation of O2*- in resistant cells compared to sensitive cells. At the same time, a strong decrease in the ESR signal of semiquinone type with a g-factor of 2.006 was observed in a culture of resistant cells grown in the absence of doxorubicin as compared with sensitive cells grown under similar conditions. At the same time, a decrease in the level of paramagnetic nitrosyl complexes of nonheme iron in resistant cells was recorded, indicating a decrease in the content of free nonheme iron as a result of the formation of drug resistance. In addition, a decrease in the level of mRNA of the transferrin receptor in resistant cells was found by the RT-PCR. These data indicate the development of a coodinated redox-dependent adaptive response, which makes itself evident as a suppression of free radical processes during the formation of resistance of K562 cells to doxorubicin.

We isolated a bioactive streptomycete from marine sediment samples collected at Bay of Bengal, India, during our systematic study of marine actinobacteria. The taxonomic studies indicated that the isolate is related to Strepomyces corchorusii. However, it differed in certain aspects, and, hence, was designated as S. corchorusii AUBN(1)/7. A solvent extraction followed by a chromatographic purification helped obtain from the isolate two cytotoxic compounds, which were identified as resistomycin, a quinone-related antibiotic, and tetracenomycin D, an anthraquinone antibiotic, on the basis of spectral data of pure compounds. They demonstrated in vitro a potent cytotoxic activity against cell lines HMO2 (gastric adenocarcinoma) and HepG2 (hepatic carcinoma) and also exhibited weak antibacterial activities against Gram-positive and Gram-negative bacteria. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2006, vol. 32, no. 3; see also http://www.maik.ru.

Drug sensitivity of tumor cells was studied in 154 children diagnosed with acute leukemia. Cellular sensitivity in acute lymphoblastic leukemia (ALL) was higher than in acute myeloid one (AML), while T-line ALL cells were more sensitive to dexamethasone than those of B-line. It was suggested that lower drug sensitivity of ALL cells at the earlier stages of cell differentiation was due to their reduced susceptibility to apoptosis. Among AML cells, M3 variant was less sensitive to cytozar while M4 - to vepeside. Reduced sensitivity to vincristine was found in series M3 > M1 - M2 > M4 while that to L-asparaginase was in M1- M2 > M4 > M3.

High doses of recombinant interleukin-2 (rlL-2) have been shown to provide clinical effect and long-term survival in patients with malignant melanoma. We have performed a phase 1 study of rIL-2 "Roncoleukin", produced in Saccharomyces cerevisiae. Twenty six patients with disseminated malignant melanoma received from 12 up to 108 millions international units (MIU) of IL-2 as 3-hour i.v. infusions days 1-5 of the 21-day cycle. From 2 to 6 patients were included on each dose level. Response was assessed according to RECIST criteria. Twenty two patients were available for response and 26 for toxicity; 68 cycles of therapy performed. No grade 4 toxicity or toxic death occurred. Main dose limiting toxicity was cardiologic, skin and constitutional (fever) symptoms. One hundred and eight MIU of "Roncoleukin" was considered the highest tolerable dose because of grade 3 toxicity in 2/2 patients, receiving this dose. One complete response (CR) and 2 partial responses (PR) were observed at dose levels of 72 MIU (1 CR and 1 PR) and 84 MIU (1 PR). 3/4 objective responses were in patients with metastases in soft tissues and lymph nodes. Overall response rate was 13.7%. "Roncoleukin" provide certain efficiency in patients with malignant melanoma. This drug has acceptable toxicity; the maximum tolerable dose is 108 MIU. Recommended dose for phase 2 clinical trails is 72 MIU.

Newly synthesized compounds, namely, platinum and palladium metal complexes based on substituted pyridinecarboxylic acids inhibit both active transport of Ca ions and hydrolysis of ATP, catalyzed by sarcoplasmic reticulum Ca(2+)-ATPase. The degree of active transport of Ca ions to vesicles correlated to the inhibition of metastases of experimental melanoma B16 by compounds studied. We suggest that the mechanism responsible for inhibition of metastases by newly synthesized compounds consists in change of normal ratio of extra- and intracellular content of Ca2+ ions that influences platelet aggregation, required for adhesion of metastasizing tumor cells to vascular walls.

Strain-specific murine lymphosarcoma RLS, resistant to apoptosis induction, was used to demonstrate that polychemotherapy (cyclophosphamide+adriamycin+cisplatin) failed to gain any significant advantage over monotherapy with adequate doses of those drugs

Esterification of 3-hydroxyl group in 11-acyloxyestra-1,3,5(10)-trienes with p-[bis(2-chloroethyl)amino]phenylacetic acid led to antitumor steroids displaying antiestrogenic and cytotoxic activities. Our substances exhibit their activities on the model of murine mammary adenocarcinoma Ca-755, with inhibition of the tumor growth being 94-99%. A new approach was used for the 11alpha-hydroxylation of estra-1,3,5(10)-trienes.