Aberrant expression of placental-like alkaline phosphatase in chronic myeloid leukemia cells in vitro and its modulation by vitamin E.

Unlabelled: Placental-like alkaline phosphatase (PLAP) is expressed by many tumors and can be detected in sera of patients with various cancers. Its aberrant expression has been considered to be potentially useful as tumor marker. However, the biological background of the role of this aberrant alkaline phosphatase (AP) in cancer is still unclear.

Vitamin Е activates expression of С/EBP alpha transcription factor and G-CSF receptor in leukemic K562 cells.

Background: Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder associated with the activity of BCR-ABL fusion oncogene. Tyrosine kinase inhibitors are the current treatment of CML, but secondary mutations finally contribute to therapy resistance and blast crisis of the disease. The search for the novel compounds for the effective control of CML is now in the spotlight.

DNA hypomethylation as Achilles' heel of tumorigenesis: a working hypothesis.

There are at least two findings that show DNA hypomethylation plays a key role in carcinogenesis. The first major evidence is that DNA hypomethylation induces target chromosomal and genomic instability with cancer manifestations. The second reason that cancer progression is associated with deepening DNA hypomethylation.

Alterations of constitutive pericentromeric heterochromatin in lymphocytes of cancer patients and lymphocytes exposed to 5-azacytidine is associated with DNA-hypomethylation.

Background: DNA hypomethylation plays a key role in carcinogenesis. The malignant transformation of cells as well as tumor progression is accompanied with increasing DNA hypomethylation in cancer cells. Nevertheless, the evolution of dis-epigenetic genomic alteration in the somatic cellular malignant transformation has not yet been clear.

[Study on secondary structure and properties of alpha- and gamma-forms of human thrombin].

Secondary structure and enzymatic properties of human a-thrombin and its gamma-form (obtaining during autolysis of the native enzyme) have been studied by differential scanning calorimetry (DSC) and circular dichroism (CD). According to DSC-data both alpha-thrombin and gamma-thrombin contained only one thermal transition peak at 58.5 and 53.

[Catalytic effect of gamma-thrombin on synthetic low molecular weight peptide substrates].

Hydrolysis and respective catalytic parameters of hydrolysis of ester peptide substrates that contain residues of hydrophobic and nonpolar amino acids in P2, P3 subsites have been studied. It is shown that efficiency of hydrolysis by thrombin is determined by the length of polypeptide chains and by the nature of the amino acids in P2, P3 subsites in the substrate. In spite of the fact that gamma-thrombin retains the conformation activity of the catalytic centre the local conformation changes of the second binding region of the enzyme have been discovered.

[Affinity chromatography of human gamma-thrombin on fibrin-agarose].

gamma-Thrombin was produced during autolysis or limited proteolysis of coagulant gamma-thrombin. This thrombin form loses its ability to coagulate fibrinogen but preserves the esterase and amidase activity on the low-molecular-weight synthetic substrates. This evidences for the integrity of the active site of gamma-thrombin and for the integrity break of the enzyme molecule region responsible for the binding with fibrinogen.

[Effect of isopropanol on the enzymatic activity and stability of thrombin].

Isopropanol is shown to affect considerably the thrombin activity. Its low concentrations (5-15%) activate the hydrolysis reaction of benzoyl-1-arginine ethyl ester (BAEE) by thrombin, whereas incomplete uncompetitive inhibition of the enzyme is observed in the presence of 20% isopropanol. Alcohol in the concentration of 25% results in complete reversible inhibition of the clothing and esterase activity of the enzyme.

[Isolation of human thrombin using affinity chromatography on gramicidin C-silochrome C 80].

Thrombin purification is conducted by biospecific chromatography on gramicidin C-silochrome C 80. Preparations possessing the fibrinogen-coagulating activity of 2500-3200 NIH units per 1 mg of protein and containing 98% of active sites are obtained. Data obtained from electrophoresis in PAAG with the presence of DS-Na show the alpha-thrombin content to be 96%; the admixture of beta-thrombin possessing no coagulating activity does not exceed 4%.