Etoposide (1 h, 25 microM) causes interphase arrest in CHO-K1 after which cells resume mitotic division and die due to apoptosis after a certain time period. Accumulation of apoptotically dying cells in the culture follows a gradual increase in the number ofmultipolar mitoses. Our findings provide the first evidence that the pattern of immunostaning for alpha-tubulin, acetylated alpha-tubulin and tyrosinated alpha-tubulin in cells dividing at various periods after etoposide treatment. Moreover, some parts of the multipolar mitotic spindle differ in the presence of antigenic determinants accessible to anti-tyrosinated alpha-tubulin antibodies. It is noteworthy that these abnormalities are aggravated just before the increase in the number of apoptotically died cells. Our findings also suggest that some cells pass through at least two mitotic cycles prior to a sharp increase in the number of apoptotically died cells in the cell culture.

The topical problem of experimental neurobiology is the development of pharmacological models to search for correlation between induced brain pathology and changes in behavioral phenotype. Cytosine arabinoside (Ara-c) is an antiproliferative agent, exposure to which in the critical period of the embryonic formation of the cortex results in the abnormality of its development. This study was aimed at estimation of the somatic and sensorimotor aspects of the early postnatal maturatrion of behavioral acts in mice with developmental abnormalities of the cortex induced by Ara-c. Pregnant C57BL/6 mice were injected with the substance on the 12.5th 13.5th gestation days. Offspring behavior was studied using a modified Fox battery on the 1st-21st postnatal days. Severe disorders of the sensorimotor development with slight somatic changes were revealed in the offsprings of Ara-c-treated mice. Features of these pathological changes point to a correlation between the developmental changes in behavioral phenotype and irregularities of the cortex formation. This experimental model can be applied to neurobiological and pharmacological studies.

We studied efficacy of a combination of intraosseous and systemic administration of drugs in patients with invasive cancer of the urinary bladder (UB). A total of 20 patients aged 54-79 years with verified had recurrence, 2 had tumors with continuous growth. T2N0M0 UB carcinoma was diagnosed in 7 patients, T3N0M0--in 12, T6N0M0--in 1 patient. All the patients received systemic chemotherapy with gemzar in a single daily dose 800-1000 mg/m2 on day 1, 7 and 14. On day 2 a single intraosseous 100 mg eloxatin was given. A total of three courses of combined chemotherapy with 4-week interval was used. Intravenous gemzar administration was accompanied with mild leukopenia in 4 patients, moderate leukopenia--in 1, allergic reaction--in 2 patients. This required gemzar discontinuation. No side effects were seen in response to intraosseous administration of eloxatin. The combined chemotherapy produced complete regression of UB cancer in 3 of 18 patients, partial regression--in 12, stabilization--in 3 patients. Neither local nor long-term tumor progression was found. Short-term therapeutic efficacy of combined therapy was 70%. Fifteen patients with partial regression or stabilization have undergone transurethral resection. Duration of a recurrence-free period reached 5 to 72 months (mean 17 months). The neoadjuvant chemotherapy proposed by us allows achievement of a high percentage of regression in patients with invasive UB cancer located in UB cervix and provides concervative surgery including patients over 70 years of age.

The review analyses contemporary data on the role of the interferon-alpha in the central nervous systems. Interferon-alpha is one of the key polyfunctional cytokines providing integrative activity of the neuro-immuno-endocrine complex. The emphasis is made on the molecular mechanisms of anti-viral, anti-proliferative and neuromodulating actions of the interferon-alpha in the brain. Mechanisms of its involvement in regulation of pain, sleep, body temperature, circadian rhythms, food consumption etc. are considered. Based on the literature and our data we hypothesized a dose-dependent action of exogenous interferon-alpha on the nervous system. We suggest that optimal schemes of chronic application of small interferon-alpha doses can be more expedient for treatment of viral or oncologic diseases than large doses causing neuropsychiatric disorders.

The aim of the work was the investigation of pharmacological activity of unique dihydroflavonol glycoside, micranthoside, extracted from the leaves Eupatorium micranthum Less. introduced into Georgia. Mature human T-cell leukemia cell lines (Jurkat) were analyzed in the study under the modeled oxidative stress. For modelling of oxidative stress 30% hydrogen peroxide (H(2)O(2)) (Sigma) (100 microM) was added to Jurkat cell incubation suspension with subsequent incubation for 24, 48 h. Under the effect of H(2)O(2) there was significant elevation of superoxide and peroxyl radical levels, as well as free NO levels, and reduced antioxidant enzyme SOD activity. It was shown that dihydroflavonol glycoside, micranthoside, extragated from Eupatorium micranthum Less., has marked antioxidant properties, it inhibits hyperproduction of reactive oxygen species, and protects cells against oxidative damage, stimulates cell proliferation and inhibits necrosis in cell line.

The basidiomycetes Ganoderma lucidum, Hericium erinaceus, Lentinus edodes and Trametes versicolor were used for preparation of aqueous extracts. A polysaccharide preparation (VPG) was isolated from the G. lucidum aqueous extracts. The mycelium was grown under submerged conditions according to an original procedure. Preliminary exposure of mice with tumors to cyclosphosphamide in a low dose for prolonged elimination of T-suppressors and rapid recovery of T-killers induced an increase in the efficacy of the H. erinaceus and L. edodes extracts. Investigation of the aqueous extracts and VPG on different tumor strain lines for the potential Modifiers of Biological Response (Ca755, s/c P388, s-180) demonstrated antitumor activity and satisfactory tolerabily after oral administration. Inhibition of the tumor growth by the H. erinaceus and T. versicolor extracts and VPG amounted to 88-99% and that of s-180 treated with the L. edodes aqueous extract amounted to 66-75%. Compositions 1, 2, 4 amd 5 were significantly more active by the duration and value of the effect on the animal tumor nodes as compared to the aqueous extracts and VPG included to the compositions and composition 4. Composition 5 (T. versicolor + H. erinaceus + G. Lucidum) proved to be the most efficient by all the criteria. The results of the design of the technologies for cultivation of the mycelum of the medicinal basidiomycetes, investigation of the antumor properties of the extracts and polysaccharide fraction of the mycelium and development of efficient compositions on their basis are summarized. Composition 5 proved to be the most promising for the clinical trials.

Mexidol therapy inhibited cyclophosphamide-induced myelosuppression in C57B1/6 line mice with Lewis lung carcinoma without affecting antitumor action of the latter. Mexidol plus cyclophosphamide proved more effective in prophylaxis of metastasis as compared with the cytostatic alone.

The report reviews the experience gained with radio- and chemotherapy-related injuries suffered by bladder cancer patients. It corroborates the opinion of most European specialists that indications for radical cystectomy be extended with due considerations of up-to-date potential in anesthesiology, extensive care and pharmacology. Possible untoward side effects of radiation and intravesical chemotherapy as well as means of solution of the problem are discussed. It is urgent considering the constantly growing number of such patients, their age and associated somatic problems.

The paper discusses the advantages offered by two regimens of therapy of Hodgkin's disease in children and adolescents (139)--DAL-HD (versions 87 and 90) (83) and SPbHD-05 (56). Survival rates were fairly high (OS--94.3%; DFS-- 90.0% and EFS--81.2%); they differed depending on risk group. Both the potential of a largen choice of prognostic criteria used in risk grading and the hazards from akylating drugs and anthracyclines were demonstrated.

The overexpression of a new cytokine-induced apoptosis inhibitor 1 (CIAPIN1) gene has been shown previously to promote a multidrug resistant phenotype in gastric cancer cells through the upregulation of MDR1 and MRP1. In the present study, we constructed the siRNA eukaryotic expression vectors of CIAPIN1 and transfected them into SGC7901/VCR cells to examine whether the down regulation of CIAPIN1 increased cell sensitivity towards chemotherapeutic drugs. After transfection, the expression of CIAPIN1 was dramatically decreased in CIAPIN1 siRNA transfectants compared with that in parental cells and empty vector control cells. The down-regulation of CIAPIN1 significantly enhanced the sensitivity of SGC7901/VCR cells to vincristine (VCR), adriamycin (ADR) and etoposide (VP-16), but not to 5-fluorouracil (5-FU) and cisplatin (CDDP). Cell capacity to efflux adriamycin decreased markedly in CIAPIN1 siRNA transfectants, and correlation between CIAPIN1 down regulation and decreased MDR1 transcriptional activity were observed. CIAPIN1 siRNA could significantly down regulate the expression of Bcl-2, and up-regulate the expression of Bax, but not alter the expression of PTEN in gastric cancer cells. These observations suggested that the siRNA constructs of CIAPIN1 we obtained could effectively down-regulate the expression of CIAPIN1 and reverse the resistant phenotype of gastric cancer cells. The further study of the biological functions of CIAPIN1 may be helpful for understanding the mechanisms of multidrug resistance of gastric cancer and developing possible strategies to treat gastric cancer.

The present review summarises the data obtained by analysing the publications dedicated to using paclitaxel-eluting stents in management of coronary heart disease. The stents containing paclitaxel (taxol) proved to have high clinical efficacy in both single and multiple stenoses of the coronary arteries. The feasibility of using taxol-eluting stents in patients suffering from diabetes mellitus and in patients diagnosed with chronic coronary occlusion does not admit of any doubt. However, the rate of restenoses development following implantation of the paclitaxel-eluting stents is higher than that after using the syrolimus-releasing stents. Unsolved as yet remains the issue concerning the efficacy of the paclitaxel-eluting stents intended for treatment of restenoses inside the stent, as well as concerning the feasibility of using these stents for stenting the main trunk of the left coronary artery.

Derivatives of the available plant triterpenes glycyrrhetic acid and betulin (betulin succinates and amides of betulonic and 18beta-glycyrrhetic acids containing fragments of long-chain amino acids and a peptide) were synthesized. The inhibitory action of these compounds on the growth of MT-4, MOLT-4, CEM. and Hep G2 tumor cells and their effect on the apoptosis of these cells were studied. It was shown that betulonic acid amides are more effective inhibitors of the tumor cell growth than the corresponding amides of glycyrrhetic acid. It was also found that betulonic acid amides containing fragments of caprylic, pelargonic, and undecanoic acids are more effective inhibitors of tumor cell growth than betulinic acid. The 17-dipeptide derivative of betulonic acid N-{N-[3-oxo-20(29)-lupen-28-oyl]-9-aminononanoyl}-3-amino-3-phenylpropionic acid exhibited the maximum inhibitory activity toward the tumor cells studied. Data on the induction of apoptosis in tumor cells by betulin derivatives at a concentration of 10 microg/ml were obtained by flow cytometry. The amides of betulonic acid proved to be the most effective inducers of apoptosis.

The paper describes the experience in using capsule endoscopy to diagnose small bowel lesions during and after chemoradiation therapy in patients with diagnosed Hodgkin's lymphoma and an attempt to compare the current views of normal tissue response to ionizing radiation, as well as drugs used for chemotherapy.

The authors discuss the present-day state of search for antitumoral compounds at Blokhin Russian Oncological Research Center and promising approaches including computer technologies as means of search for new anticancerous targets and drugs.