The influence of the vaccine Immunovac-VP-4, prepared from the antigens of opportunistic microorganisms, on the proliferative and cytotoxic activity on peripheral blood mononuclears (PBMN) from healthy donors in vitro and on spleen cells of CBA mice in vivo during their incubation with Cisplatin was studied. VP-4 produced a dose-dependent, stimulating effect on the proliferative potential of PBMN and, when used in the highest of all tested doses (20 microg/ml), increased the Cisplatin-suppressed proliferative activity of PBMN in 9.4-fold. VP-4 increased the cytotoxic activity of PBMN on tumor line cells K-562 (38,4 to 60.1%) and increased the cytotoxic effect of Cisplatin (68.18 to 87.56%). A single injection of VP-4 to mice stimulated the proliferative activity of spleen cells, studied ex vivo, units and partially restored their cytostatic-suppressed activity. The cytotoxic action of the spleen cells of immunized mice on tumor line cells YAC-1 was twice as great as that of spleen cells taken from intact animals and potentiated the cytotoxic action of Cisplatin. The mechanism of increasing the proliferative activity and cytotoxic effect of monomuclears under the influence of vaccine VP-4 is seemingly linked with the synthesis of cytokines, influencing the lymphokine-activated cytotoxicity of lymphocytes.

A rare case of aspergillesis sepsis in an one month old baby with inborn leukemia is reported. Of essential importance in the pathology is genetic deficiency of this child, decreased immunity and a grave intoxication due to leukemia chemotherapy.

The subjects of the study (105 patients with blood system tumors), were divided into 4 groups. The patients of the first group received only cytostatic therapy. The subjects of the second, third and fourth groups were administered a combination of cytostatic and antibacterial agents. In addition to this, the patients of the third and fourth groups received prebiotic preparations as means of corrective therapy. The results obtained by measurement of short-chain fatty acids (SCFA) in feces by means of liquid-gas chromatography were used as criteria for evaluation of the therapy influence on intestinal microflora. The study shows that the cytostatic and combined treatment worsen the disbalance between aerobe and anaerobe populations, which manifests in SCFA spectrum alteration. Use of prebiotic preparations results in improvement of intestinal microflora condition or prevents the aggravation of its disturbance caused by the treatment of the fundamental illness, which becomes apparent in stabilization or normalization of SCFA profile in feces. Study of SCFA makes it possible to monitor microbiocenosis, adjust corrective therapy individually and evaluate its effectiveness.

After the transfection of the gene Bax into the cultured tumor cells of human ovary adenocarcinoma SKOV3 and uterus carcinoma HeLa in vitro the high sensitivity of the cells SKOV3 to the protein Bax produced after the gene Bax transfection was found. The sensitivity of the cells HeLa to the gene Bax transfection was much smaller. The hyperexpression of gene Bax and hypersensitivity to doxorubicin were seen in HeLa cells received as a result of the gene Bax transfection and subsequent selection. All cells of the line SKOV3 with the increased expression of the transfected gene Bax died. In the cell line SKOV3 the mutation in a gene Bax was found which has a genotype G7/G9 against a native type of a gene Bax--G8/G8. It was concluded that the found in the exone 3 of the gene Bax mutation G7/G9 in cells SKOV3 results in an inactivation of proapoptotic activity of the protein Bax.

Molecular properties and possible mechanisms of action of cytotoxic ribonucleases (RNases), potential antitumor therapeutics, are characterized. The analysis of recent publications and own experimental results have allowed the authors, on the one hand, to distinguish cellular components that are responsible for selective activity of exogenous RNases towards malignant cells, and on the other--to identify the contribution of definite molecular determinants to the enzyme cytotoxicity. The predominant effect of the RNase molecule charge on the cell death induction is shown. The RNase cytotoxic effects are caused by catalytic cleavage of available RNA, by products of its hydrolysis, as well as by non-catalytic electrostatic interaction of exogenous enzyme with cell components. Potential targets for RNase action in a cancer cell have been revealed. The role of modulation of the membrane calcium-dependent potassium channels and ras-oncogene functions in the RNase-induced cell damage is defined. The effect of cytotoxic RNases on gene expression via influencing the RNA interference is discussed.

Olipiphat, which is experimentally capable of antitumor action, did not induce any immediate hypersensitivity, but lowered such response to horse serum; nor did it stimulate delayed hypersensitivity to full Freund adjuvant or sharp venous return after concavalin A. No skin or eye mucosa irritation was reported.

Retinoic acid (RA) causes differentiation of mouse F9 embryonic carcinoma cell line into primitive and parietal (with dibutiril-cAMP) endoderm. The role of AP-1 transcription factor during RA-induced differentiation was studied in F9 cell line. It was shown that differentiated cells acquired protein complexes, which are specifically bound to well characterized AP-1 32P-labeled binding sites from collagenase (Col-AP-1) and c-jun (Jun2-AP-1) promoters. These complexes contain c-Fos/c-Jun with Col-AP-1 site and c-Jun/ATF-2 with Jun2-AP-1 site as revealed by supershift analysis. DNA-binding activity of these complexes is high in parietal endoderm but low-detectable in undifferentiated cells. DNA-binding activity of AP-1 transcription factor correlates with increased expression of c-fos and c-jun genes. RT-PCR analysis showed an increase in steady-state level of c-fos and c-jun gene transcription at the stage of parietal endoderm (terminally differentiated F9 cells). Transcription of immediate early c-fos and c-jun genes and DNA-binding activity of c-Fos/c-Jun complex are serum dependent. The rate of c-fos and c-jun gene transcription and DNA-binding activity of c-Fos/c-Jun complex decreased in serum-starved cells, but was rapidly induced upon stimulation with serum. Undifferentiated F9 cells contain a very low level of c-fos mRNA, with may be a consequence of repressive chromatin structure in promoter region. Histone deacetylase (HDAC) activity is necessary to restrict expression of specific number of genes, also HDAC inhibitors are well known inductors of differentiation and anticancer agents. Frow cytometry analysis showed a decreased rate of proliferation of F9 cells after their incubation with HDAC inhibitors, sodium butirate and trichostatin A. Also, these ihibitors induced the transcription of c-fos gene. So, we conclude that HDAC activity may be necessary to sustain a high proliferative rate of undifferentiated F9 cells.

The STAT transcription factors (signal transducers and activators of transcription), STAT1 and STAT3, are involved in signal transduction from growth factors and different cytokine receptors. STAT1 and STAT3 activation mechanisms are not sufficiently investigated, but they are known to depend upon both cell type and stimulus for either of them. Recently, we have shown that nocodazole blocked EGF-induced STAT1 transport to the nucleus. Here, we have compared STAT1 and STAT3 activation in response to IFNgamma, IFNalpha and epidermal growth factor (EGF) in A431 cells. We have shown the STAT1 activation by all these agents; unlike, STAT3 was activated by EGF only. STAT1 and STAT3 activation upon EGF is blocked by both nocodazole and Src-kinase family inhibitor. STAT1 activation upon IFNgamma influence is blocked by nocodazole, but does not depend on the activity of Src-family kinases. The increased STAT3 phosphorylation results from a combined action of Src-kinase inhibitor and IFNgamma. IFNalpha-induced activation of STAT1 was not inhibited by either nocodazole or Src-kinase inhibitor. Taken together, the data obtained suggest that the activation of both STAT1 and STAT3 in A431 cells is accomplished by different mechanisms.

Infection is one of the main causes of death in patients with hemoblastoses. Within the last years there was observed an increase in the ratio of fungal infections in the structure of mortality among hematologic patients with neutropenia. The present study was aimed at comparative estimation of the efficacy of the prophylactic use of various azole antifungal agents in patients with hematologic neoplasms and severe neutropenia. The trial enrolled 88 patients comparable by the diagnosis and chemotherapy characteristics, in whom severe neutropenia developed after intensive therapy. Antifungal drugs were used prophylactically when the neutrophil count lowered below 1.0 x 10(9)/l until its increasing above 1.0 x 10(9)/l or when the signs of fungal infection were evident. Itraconazole was used in cyclodextrin solution in 30 patients in a dose of 0.2 g orally twice a day and fluconazole was used in capsules in 24 patients in a dose of 0.2 g orally once a day. The results were compared with those of the ketoconazole use in a dose of 0.2 g orally twice a day (n = 34). The frequency of fungal infection proved by the clinical documentation was 20.5% in the ketoconazole group (k) (7 out of 34 patients), 8.3% in the fluconazole group (f) (2 out of 24 patients) and 6.6% in the itraconazole group (i) (2 out of 30 patients), p (k-f) = 0.21, p (k-i) = 0.11 and p (f-i) = 0.74. The frequency of fungal infection proved by the microbiological documentation was statistically much higher in the ketoconazole group (38.2%) vs. the fluconazole group (8.3%) (p = 0.013) and the itraconazole group (6.6%) (p = 0.004). The prophylactic use of itraconazole and fluconazole was efficient in preventing development of invasive mycoses in the patients with hemoblastoses and severe neutropenia. Their efficacy was much higher than that of ketoconazole.

The paper deals with a clinical evaluation of the results and side-effects of hormonotherapy of 108 patients with prostatic cancer, aged 46-96. Among the most frequent side-effects were: gynecomastia, sexual and neurologic dysfunction. Ziproterone acetate was followed by less frequent side-effects than generic flutamide. Monotherapy was tolerated better than maximum androgen deprivation. No significant correlation was found between survival, lethality and serologic progression duration, on the one hand, and variety of antiandrogen or androgen deprivation technique, on the other.

An assessment of the densitometry data on 76 patients established a progressively falling level of minerals in the skeleton as a result of treatment with hormones for prostate cancer. The basal mineral levels had been identified by means of dual-energy X-ray absorptiometry. While said changes were immediately caused by maximum androgen deprivation, tumor influence and medication contributed too.

The potential of increased antitumor effect of cyclophosphane used in conjunction with low-energy infra-red laser radiation was studied in sarcoma-45--bearing rats. Exposure to certain modes stimulated non-specific antitumor resistance and enhanced antitumor influence of the drug by reducing its damaging effect. Also, it inhibited refractory leukopenia and marked intoxication induced by antistressor reactions.

Diabenol, a new Russian antidiabetic drug, was used to investigate its effect on 1,2-dimethylhydrazine (DMH)-induced carcinogenesis in rat large gut. Five doses of 21 mg/kg DMH were injected at an interval of one week. Administration of 10 mg/kg diabenol with drinking water had no effect on either body mass or feed and water consumption. Yet, it was followed by a significant decrease in tumor incidence (4.22 vs. 5.77 tumors per tumor-bearers), frequency of neoplasms in the ascending colon (40.0% vs. 89.5%) and in their number (0.60% vs. 1.63 tumors per rat in a group). In the other groups, those indices tended to be still lower. Another tendency characteristic of the experimental group was a significantly high percentage of exophytic tumors (76.3% as compared with 50% in control) consisting of well-differentiated cells (47.4% and 14.7%, respectively) and with predominantly shallow invasion into the gut wall. Our results suggest the ability of the drug to inhibit DMH-induced carcinogenesis in the rat large gut.

A basically new system has been developed to screen carcinogens in Drosophilidae, which is based on somatic mutagenesis and recombination. The system may induce tumors in Drosophilidae, which are recorded in adult insects. The test uses recessive mutation in the suppressor gene of growth of warts (wts) tumors. The new system is sensitive to a wide spectrum of mutagenic carcinogens that are naturally encountered. The sensitivity of the system to polycyclic aromatic hydrocarbons and aromatic amides is higher than that of classical tests. Dominant p53 gene mutation that ceases mutagen-induced apoptosis has been shown to increase the incidence of wts tumors by many times. The magnitude of the effect depends on the rate of mutant p53 expression. The increasing effect of p53 mutation extends to both somatic recombination and point mutations and deletions at the wts locus.

Phophatidylinositol-3-kinase (PI3K) is a major intracellular protein that is responsible for the transmission of an antiapoptotic signal and controls the survival of tumor cells upon exposure to damaging agents. Experiments using different tumor cell cultures have shown that the resistance of cells to the antiproliferative action of dexamethasone, caused by their long cultivation with the hormone, is associated with the activation of PI3K and the transcription factor STATS. The activation of PI3K and STAT3 in the dexamethasone-resistant cells correlates with the increase in the total thyrosine kinase activity and with the decrease in the sensitivity of cells to exogenous proliferative agents, such as 17beta-estradiol. The long exposure of hormone-sensitive cells to nonhormonal factors that activate the PI3K/STAT3 signaling pathway, hypoxia in particular, has been shown to suffice to reduce the degree of hormonal tumor cell dependence. VEGF-A, an angiogenic peptide whose action was partially realizes through the PI3K-signalling pathway, has been demonstrated to be involved in the maintenance of cell growth, including the growth of hormone-independent cells. The findings suggest that complex changes in the antiapoptotic and mitogenic signaling pathways associated with PI3K, which ensures the autonomic, hormone-independent growth of tumor cells, may underlie the decreased hormonal dependence of tumor cells. Whether PI3K may be used to suppress the growth of hormone-independent tumors is discussed.

The paper shows the role of tumor cell apoptosis induction in the mechanism of cancer cytoreductive therapy and the significance of the impaired cell death program for the pathogenesis of the phenotype of multidrug and radiation resistance resulted from the use of specific antitumor therapy and from the natural course of tumor progression.

The effects of the natural avermectin complex, aversectin C and individual avermectin B1 on the growth of ascitic and solid transplantable tumors in animals were studied. The results showed for the first time that both aversectin C and avermectin B1 possessed marked antitumor activity. In subtoxic doses aversectin C significantly inhibited the growth of P388 lymphoid leukemia and Ehrlich carcinoma, both ascitic and solid ones. In some administration regimens aversectin C inhibited the tumor growth by 70 to 80%. The highest effect of aversectin C was observed after its intraperitoneal administration. Avermectin B1 inhibited the growth of solid Ehrlich carcinoma and carcinoma 755.