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Biomedical subjects

T V Bykova

Publications and source records attributed to T V Bykova.

11 recordsLinked to original sources

[Induction of premature senescence program by an inhibitor of histone deacetylase sodium butyrate in normal and transformed rat fibroblasts].

We investigated a possibility to induce the premature cell senescence in rat embryo fibroblasts and E1A + cHa-ras transformants. We found that after the treatment with sodium butyrate, an inhibitor of histone deacetylases, both normal and transformed cells completely stopped to proliferate and accumulated at G1/S and G2/M phases of the cell cycle. The cloning efficiency data show that the cell cycle arrest induced by sodium butyrate is irreversible and correlates with the accumulation of active phosphorylated form of stress kinase p38, and with the expression of marker of senescence--beta-galactosidase activity (SA beta-Gal). The program resembling the premature senescence after sodium butyrate treatment is supposed to develop both in normal and transformed cells. The irreversible block of proliferation in E1A + cHa-ras transformants may be regarded as an example of activation of anticancer program like that of premature senescence in the tumor rodent cells.

Animals↗

[MAP-kinase cascade analysis in transformed cell with different abilities to make G1/S block under serum starvation].

We have studied the ability of ERK1,2, JNK1,2 and p38 kinases to be regulated after serum deprivation in E1A + E1B-19 kDa- and E1A + E1A + c-Ha-ras-transformed rat embryo fibroblasts. It was demonstrated that oncogene transformation resulted in an increase of total kinase content independently of the type of complementing oncogene. However, for ERK1,2 kinases phosphorylation was found to depend on the type of complementing oncogene. Besides, unusual biphasic character for ERK1,2 kinases phosphorylation was checked in control fibroblasts REF52 and in transformed E1A + E1B-19 kDa cells, which undergo G1/S arrest after a 24 h serum starvation. According to the immunoblotting data, phosphorylated forms of ERK1,2 kinases are not detected after 15-30 min of serum deprivation, but their content is restored up to the control level within several hours. At the same time, the level of ERK1,2 phosphorylation in E1A + c-Ha-ras cells did not change after serum withdrawal. Besides, serum deprivation did not lead to significant changes in the level of phosphorylation of both type stress kinases--JNK2 and p38 in all types of studied cells. We discuss possible mechanisms of biphasic alteration in ERK1,2 phosphorylation level under condition of serum deprivation of REF52 cells and E1A + E1B-19 kDa-transformed fibroblasts, able to be arrested in G1 phase.

Adenovirus E1A Proteins↗

[The MDR gene and cellular sensitivity to various effects].

mdr-Transfected K-562 cells revealed a relatively high resistance to cytotoxic monokines and ionizing radiation as compared to parental cells. Taken together with what is known about the resistance of mdr-expressing cells to multiple cytotoxic drugs, our results point to malignant cells having universal mechanisms of chemo-, bio- and radioresistance.

Cell Division↗

[The clinical significance of MDR-1 gene expression in the hemopoietic cells of patients with acute leukemias in different phases of the disease].

AIM: Analysis of cytostatic therapy effects on expression of gene MDR-1 in hemopoietic cells of patients with acute leukemia (AL) in complete clinicohematological remission (CCHR). MATERIALS AND METHODS: The study included 48 AL patients. 27 of them were untreated, 25 were resistant to or had recurrent AL. 4 patients were followed up. Bone marrow mononuclear fraction was investigated. Expression of MDR-1 gene in the cells was evaluated at hybridization. RESULTS: High expression of MDR-1 gene occurred in leukemic blast cells either upon achievement of CCHR or at least 6 months after its onset. When using schemes of chemotherapy containing two potential inductors of gene MDR-1, expression of this gene was registered significantly more frequently than in using schemes based on one inducing drug (p < 0.05). Frequency of occurrence of enhanced expression of gene MDR-1 in leukemic blasts significantly correlated with frequency of CCHR (p < 0.05). Correlation between occurrence of the gene's expression in normal hemopoietic cells in CCHR and occurrence of early AL recurrences was not found. CONCLUSION: The findings may facilitate design of new AL treatment programs.

Antineoplastic Combined Chemotherapy Protocols↗

[Hyperexpression of the multiple drug resistance gene (MDR-1) in chronic myeloleukemia patients].

AIM: To elucidate prognostic value of MDR-1 gene expression in patients with chronic myeloid leukemia (CML). MATERIALS AND METHODS: The MDR-1 gene expression was studied by in situ hybridization in hemopoietic cells of 63 Ph-positive CML patients in different phases of the disease. The survival of the patients and duration of the chronic phase (CP) were evaluated using the Caplan-Meyer method. RESULTS: MDR-1-positive patients had a shorter survival (p < 0.01) and CP (p < 0.05) than negative ones. MDR-1 gene overexpression has no impact either on the survival or duration of AP and BP (p < 0.05). Moreover, the MDR-1 gene overexpression is not dependent either on the previous treatment or other prognostic markers. CONCLUSION: Overexpression of MDR-1 gene is an independent prognostic factor and an additional parameter to Sokal's scores.

Adolescent↗

[Immunomodulating therapy in perforated peritonitis].

The immunological responsiveness was studied in 160 patients with generalized peritonitis. In the postoperative period, 51 patients underwent immunomodulating therapy. The highest effect was produced by transfusion of 300-400 ml leukoconcentrate.

Adjuvants, Immunologic↗

[Prediction of infectious complications in surgical patients].

An analysis of results of intracutaneous tests with a set of microbe allergens in 121 patients has shown that absence of a skin reaction to all the allergens under test demonstrates a disturbed immune response (incidence of infectious complications was 77%, both lethal outcomes included). The selective hypersensitivity to the injection of certain allergens was due to the carrier state. The normal reaction of slow type hypersensitivity was found in 101 patients (86,4%) and showed no disorders in immune reactivity which was confirmed by the postoperative course without complications. The test of the slow type hypersensitivity is considered to be highly informative and to allow prognosis of postoperative complications.

Antigens, Bacterial↗

[Plasma protein spectrum of dog blood during treatment of hypoxia with a Sever-OMR membrane oxygenator].

A Sever-OMP membrane oxygenator (MO) was applied in experiments on 12 dogs to the treatment of a severe hypoventilation hypoxia (over 3 hours). The MO was connected to the arteriovenous shunt established on the femoral vessels. The blood plasma protein spectrum (BPPS) was determined electrophoretically before and after MO connection. BPPS of dogs is characterized by a number of specific features. No signs of blood plasma protein denaturation were found during operation of the Sever-OMP MO that ensures adequate conditions for body existence under hyperventilation. Studies on BPPS facilitate the appraisal of the MO and perfusion conditions.

Animals↗