Biomedical subjects

T A Korolenko

Publications and source records attributed to T A Korolenko.

At least 19 recordsLinked to original sources

PubMed2005

Effect of cysteine protease inhibitor Ep-475 on TNF-alpha-independent cyclophosphamide-induced apoptosis in mouse lymphosarcoma LS cells.

Cyclophosphamide 1.5-2.0-fold increased activity of cathepsins B and L in tumor tissue of mouse lymphosarcoma LS and caused tumor regression. The effect was most pronounced on day 5 after treatment. Twofold treatment with a selective cathepsin inhibitor Ep-475 slightly stimulated tumor growth in control mice and significantly reduced the antitumor effect of cyclophosphamide. Lysosomal cysteine proteases cathepsins B and L are involved, but do not play a key role in TNF-alpha-independent apoptosis in LS cells induced by cyclophosphamide.

Animals↗

PubMed2005

Stimulation of macrophages increases, while suppression of these cells inhibits metastatic dissemination of two transplantable mouse tumors in the liver and lungs.

Stimulation of mouse tissue macrophages with carboxymethylated beta-(1-->43)-D-glycan 1 day before intravenous injection of tumor cells increased the number and weight of implants (experimental metastases) of mouse hepatocarcinoma and adenocarcinoma in the liver and lungs, respectively. Suppression of liver macrophages with gadolinium chloride or sequestration of cells during intraperitoneal administration of macrophage attractants inhibited metastatic dissemination of hepatocarcinoma and adenocarcinoma in the liver and lungs, respectively. In the latter case animal lifespan increased. Our results indicate that at certain stages of metastatic dissemination, activation of mononuclear phagocytes can stimulate the formation and growth of metastases.

Adenocarcinoma↗

PubMed2004

Effect of liver macrophage depression on the development of liver metastases of HA-1 tumor in mice.

Gadolinium chloride (5 mg/kg) administered to mice 24 h before intravenous transplantation of HA-1 hepatoma cells decreased the volume density of tumor implants in the liver, reduced the intensity of degenerative and necrotic changes developing under the effect of growing tumor metastases, and prolonged the life span of tumor-bearing mice. Development of metastases was not associated with changes in cathepsin B activity in the liver, while activity of cathepsin L decreased only during the early period (4 days) after injection of gadolinium chloride. Injection of gadolinium chloride led to labilization of liver cell lysosomes because of overload with gadolinium chloride particles. The positive effect of gadolinium chloride was probably associated with depression of liver macrophages at the stage of tumor cell invasion and with subsequent migration of monocytes/macrophages preventing the growth of formed metastatic nodes in the liver.

Animals↗

PubMed2004

Effect of polysaccharides and human plasma lipoproteins on the secretion of cystatin C by peritoneal macrophages from normal and tumor bearing mice.

Intact peritoneal macrophages in vitro secreted the cysteine proteinase inhibitor cystatin C. Polysaccharides stimulated cystatin C secretion: lipopolysaccharide < carboxymethylated beta-D-glucan < sulfoethylated beta-D-glucan. Human plasma low-density- (LDL) and high-density lipoproteins (HDL) are still more potent inducers of cystatin C secretion by macrophages. Peritoneal macrophages from mice with experimental HA-1 hepatoma compared to those from intact mice secreted more cystatin C with maximum polysaccharide-stimulated secretion after 30 min of incubation. LDL and HDL induced cystatin C secretion by tumor macrophages also.

Animals↗

PubMed2003

Cystatin C and cysteine proteinases during the development and therapy of Lewis lung adenocarcinoma in mice.

We measured plasma cystatin C concentration and activity of cathepsins B and L in tumor tissue as possible markers for the efficiency of antitumor therapy and prognostic criteria for Lewis lung adenocarcinoma in mice. Plasma cystatin C concentration markedly decreased in mice with tumors. During successive therapy the increase in plasma cystatin C concentration correlated with the degree of inhibition of tumor growth. Activities of cathepsins B and L in the liver increased in animals with tumors. In mice receiving successive antitumor therapy activities of cathepsins B and L increased in tumor tissue, but decreased in the liver (compared to untreated animals).

Animals↗

PubMed2003

Cystein proteinase inhibitor stefin A as an indicator of efficiency of tumor treatment in mice.

The concentration of stefin A (cystatin A in mice) was measured in animals with experimental tumors (LS lymphosarcoma, HA-1-hepatoma, and Lewis lung carcinoma) during effective antitumor therapy. In mice with these tumors serum concentrations of stefin A increased, while the concentration of cystatin C (extracellular cystein proteinase inhibitor) decreased. The concentration of stefin A in tumor tissue in Lewis lung carcinoma was higher than in LS lymphosarcoma and HA-1-hepatoma ascitic cells, which can be explained by the degree of their malignancy. The content of stefin A in tumor tissue was similar to that in the liver and spleen of tumor-bearing animals, while its concentration in the liver and spleen of tumor-bearing animals was lower than in intact mice. The level of stefin A is an important marker of malignancy and an indicator of the efficiency of antitumor therapy.

Animals↗

PubMed2003

Mouse lymphosarcomas sensitive and resistant to cyclophosphamide therapy: activity of cathepsins B, L, and D during various schemes of treatment with cyclophosphamide and SE-glycan.

We measured activities of cysteine (cathepsins B and L) and aspartyl proteinases (cathepsin D) in tumor tissue of mice with sensitive and resistant lymphosarcomas. In cyclophosphamide-resistant lymphosarcoma tissue activities of cathepsins B, L, and D were lower than in cyclophosphamide-sensitive lymphosarcoma. After treatment with cyclophosphamide in high doses enzyme activities in mice with cyclophosphamide-resistant lymphosarcoma increased more significantly than in animals with cyclophosphamide-sensitive lymphosarcoma. Sulfoethylated beta-1,3-D-glycan potentiated the effect of cyclophosphamide in mice with both forms of lymphosarcoma. This drug in the lowest dose (10 mg/kg) was most effective.

Adjuvants, Immunologic↗

PubMed2003

[Immunoenzyme technique for analysis of cystatin C in serum of patients with hemoblastosis].

Cystatin C is a low-molecular endogenous inhibitor of cysteic proteinases. Sets for immune-enzyme assay of cystatin C in human blood serum (KRKK, Slovenia) were made used of in the case study. The concentration of cystatin C (CCC) in blood serum was found to be higher in cases of certain hemoblastoses (Non-Hodgkin's disease, lymphogranulomatosis and multiple myeloma), with the highest concentration of the inhibitor being observed in patients with resistance to the conducted polychemotherapy and a poor prognostication. The treatment of Non-Hodgkin's disease and of lymphogranulomatosis brought about a normalized CCC in blood serum. It was suggested that CCC in blood serum reflects a nature of tumor growth and, obviously, it can be a criterion in assessing the therapy efficiency. The concentration of alpha 1-proteinases inhibitor remained unchanged before and after treatment.

Acute Disease↗

PubMed2003

[Comparative characteristic of serpin--alpha-1 proteinase inhibitor in human and mice serum].

Serpin alpha-1-proteinase inhibitor have been studied in human subjects and in mice of different lines as acute phase reactant and during tumor development. In humans, there was no difference of serpin activity between men and women. Increased activity was noted in men with acute trauma (acute phase reaction). Comparatively to male, in female mice of different lines decreased activity of serum alpha-1-proteinase inhibitor, was shown. There was no increase of alpha-1-proteinase inhibitor activity during inflammation induced by zymosan administration in mice. alpha-1-proteinase inhibitor belongs to acute phase reactants in humans but not in mice; for mice alpha-2-macroglobulin is a more typical acute phase reactant as compared to alpha-1-proteinase inhibitor. Murine tumor development (hepatoma HA-1, lymphosarcoma LS, Lewis lung adenocarcinoma) was followed by a decreased activity of serum alpha-1-proteinase inhibitor both in successfully treated and untreated groups. According to data of literature, similar dated were obtained in humans with tumors. It was suggested that changes of expressiln of alpha-1-proteinase inhibitor by tumors and its secretion were involved in decreased activity of alpha-1-proteinase inhibitor.

Adolescent↗

PubMed2002

Activity and concentration of cathepsin B as prognostic criteria for the development of mouse LS lymphosarcoma and Lewis lung adenocarcinoma.

We measured activity and content of cathepsin B in tumor tissues, liver, and spleen in mice with Lewis adenocarcinoma and LS-lymphosarcoma. Cathepsin B activity in Lewis adenocarcinoma cells was lower than in LS-lymphosarcoma cells, which was probably related to differences in their metastatic properties. Antitumor therapy increased activity and content of cathepsin B in tumor tissues. Changes in the content and activity of cathepsin B in tumor tissues can serve as a prognostic criterion for tumor regression during therapy. Cathepsin B is probably involved in apoptosis of tumor cells during chemotherapy of lymphosarcoma-LS with cyclophosphamide.

Animals↗

PubMed2001

Role of cystatin C and cysteine proteinases in the development of mouse LS-lymphosarcoma.

The growth of LS-lymphosarcoma in CBA mice was accompanied by a decrease in the content of the major extracellular inhibitor cystatin C in the tumor, plasma and, to a lesser extent, in tissues not involved in tumor process (liver and spleen). Cyclophosphamide in a dose of 50 mg/kg prolonged the life-span of animals and decreased tumor size by 80%. Cathepsin B and L activities in the tumor tissue increased by 3 and 7 times, respectively. Cystatin C content in the tumor tissue, spleen, and plasma also increased. Cystatin C assay in tumor tissue and plasma helps to predict the rate of tumor growth and to evaluate the efficiency of antitumor therapy.

Animals↗

PubMed2001

Macrophage Stimulator beta-(1-->3)-D-carboxymethylglucan improves the efficiency of chemotherapy of Lewis lung carcinoma.

We studied the effect of macrophage stimulator water-soluble beta-(1-->3)-D-carboxymethylglucan on the efficiency of cyclophosphamide chemotherapy in Lewis lung carcinoma. Cyclophosphamide inhibited the growth of primary tumor nodes by 57%. The preparation possessed pronounced antimetastatic activity: metastases were found in 40.9% animals. Combination therapy with cyclophosphamide and (1-->3)-beta;-D-glucan inhibited the growth of intramuscular tumors by 75-89% and reduced the incidence of metastases into the lungs by 92-94%. The therapeutic effect was most pronounced after simultaneous administration of these preparations: tumor growth was suppressed by 89.3% and metastases were found in only 7.5% animals (vs. 100% in the control). The potentiating effect of beta-(1-->3)-D-carboxymethylglucan is related to accumulation of cysteine proteinase inhibitors in the tumor tissue and plasma, but not to changes in blood cell composition.

Animals↗

PubMed2001

Acute phase proteins as biological markers of addictive disorders in teenagers and children.

Acute phase proteins (APP), including C-reactive protein (CRP), alpha-1-proteinase inhibitor (PI) activity and albumin level were studied in serum of 183 teenagers and children with drug addictive disorders (DAD) (mainly home-made opiate dependence and glue-sniffing), hospitalised at Municipal Drug Addictive Centre, Novosibirsk (1996-1999). Serum CRP concentration increased several times during early withdrawal period in the teenager group with opiate dependence. In most cases of DAD decreased level of albumin (negative APP reactant) as well as decreased activity of PI was revealed. After treatment (about 21 days after onset of hospitalisation) the level of albumin still remained decreased. These indexes were suggested as a possible surrogate biological marker of DAD, and immune-stimulators were recommended during DAD treatment to restore the decreased level of protective APP of these patients.

Acute-Phase Proteins↗

PubMed2000

Chitotriosidase as a marker of macrophage stimulation.

Serum chitotriosidase activity was determined in different conditions accompanied by macrophage stimulation. Stimulation of macrophages with zymosan, yeast polysaccharide carboxymethylglucan (fraction II), and lysosomotropic preparation Triton WR-1339 1.5-2.0-fold increased enzyme activity. Chitotriosidase activity in intact Wistar rats was similar to that in humans, while in CBA and A/Sn mice this parameter was 5-fold higher. Sharp increase in chitotriosidase activity in the serum from patients with type I Gaucher's disease was probably related to intense secretion of the enzyme by macrophages. Under experimental conditions, stimulation of rat and mouse macrophages (mainly liver cells) caused no increase in chitotriosidase activity typical of patients with Gaucher's disease.

Adolescent↗

PubMed2000

Chitotriosidase as a new marker of macrophage stimulation in a tumor model treated with cyclophosphamide and Ukrain.

Ukrain has previously been demonstrated to exert a malignotoxic effect in vivo. This antitumor drug has been effective in the treatment of some malignancies in experimental animals as a result of immunostimulation (macrophage stimulation). In the present study, serum chitotriosidase activity was measured as a biochemical marker of macrophage stimulation in several murine and rat models of macrophage stimulation. It was shown that zymosan, carboxymethylated glucan and Triton WR 1339 administration to CBA mice or Wistar rats was followed by a considerable increase in serum chitotriosidase activity. Murine LS lymphosarcoma development decreased serum chitotriosidase activity. Antitumor treatment by Ukrain or cyclophosphamide did not restore this index to the normal value.

Alkaloids↗

PubMed2000

Cystatin C in LS lymphosarcoma and HA-1 hepatoma treated with Ukrain and cyclophosphamide and involvement of apoptosis.

The concentration of cystatin C, a cysteine proteinase inhibitor, was measured during the treatment of murine LS lymphosarcoma with cyclophosphamide and HA-1 murine hepatoma with the antitumor drug Ukrain. It was shown that concentrations of cystatin C were very low in both the tumor tissues studied (HA-1 hepatoma cells and LS lymphosarcoma); increased cystatin C concentrations were found only in Ukrain-treated murine hepatoma, suggesting the mechanism of antitumor effect of this drug. Cyclophosphamide treatment in LS lymphosarcoma did not influence the concentration of cystatin C in tumor cells. At the same time, a marked increase in cathepsin B and cathepsin L activity in LS lymphosarcoma was found, indicating the involvement of apoptosis in the mechanism of antitumor action of cyclophosphamide. While the DNA from untreated LS lymphosarcoma was very homogenous and its molecular weight was high, the DNA from tumors of treated mice broke down, giving rise to the ladder figure characteristically produced by cells dying from apoptosis. Evidence was obtained that cyclophosphamide-induced tumor regression was effected by apoptosis.

Alkaloids↗

PubMed2000

Influence of Ukrain and cyclophosphamide administration on HA-1 murine hepatoma and LS lymphoma on aspartic proteinase cathepsin D.

Cathepsin D, the major lysosomal aspartyl proteinase and a mediator of interferon-gamma and tumor necrosis factor-alpha-induced apoptosis, was studied in murine models of LS lymphosarcoma treated by cyclophosphamide (possible apoptosis induction), and HA-1 hepatoma treated by Ukrain (positive antitumor effect). It was found that cyclophosphamide, as well as cyclophosphamide plus Ukrain, increased cathepsin D specific activity in mice with LS lymphosarcoma. Ukrain alone had no effect on cathepsin D activity in LS lymphosarcoma. In HA-1 hepatoma cells cathepsin D activity was not changed compared with intact normal murine liver (day 10) and activity decreased during tumor development (on day 12). Ukrain significantly increased cathepsin D activity in ascitic fluid (day 10) and had a tendency to increase cathepsin D activity in ascitic cells but not to the normal value.

Alkaloids↗

PubMed2000

Cysteine proteinase inhibitor level in tumor and normal tissues in control and cured mice.

Cystatin C is the best known extracellular endogenous cysteine proteinase inhibitor and has been studied as a possible index of tumor growth and as a marker of the effectiveness of antitumor therapy. The aim of this study was to evaluate cystatin C concentrations in murine tumor tissues (compared with other organs not directly involved with tumor development, such as the liver and spleen) during treatment with several antitumor drugs (Ukrain and/or cyclophosphane). Cystatin C concentrations in murine tissues and biological fluids was determined by enzyme-linked immunosorbent (ELISA) assay. The cystatin C ELISA test is a sandwich immunoassay, which uses immobilized rabbit antihuman cystatin C Pab and mouse antihuman cystatin C Mab-HRP (monoclonal antibodies, conjugated with horseradish peroxidase). We observed decreased serum cystatin C concentrations compared with controls in all nontreated tumor models: HA-1 hepatoma (solid and ascitic forms), lung adenocarcinoma (solid and ascitic forms) and LS lymphosarcoma. In the ascitic fluid of mice with HA-1 hepatoma the cystatin C concentration was much lower than in the serum of the same mice (about 20-fold lower). In the HA-1 model of hepatoma cells cystatin C concentration decreased about 2-3-fold compared with the control (intact liver) and Ukrain significantly increased the cystatin C concentration. Cyclophosphane treatment of LS lymphosarcoma significantly increased the cystatin C concentration in serum. Cyclophosphane treatment (50 mg/kg, single injection) increased cystatin C by up to 8-fold more in tumor issue. Ukrain treatment of LS lymphosarcoma was also followed by increased levels of cystatin C in tumor tissue (4-fold); cyclophosphane plus Ukrain had a similar positive effect. In the group with LS lymphosarcoma Ukrain or cyclophosphane plus Ukrain treatment induced a significant increase in cystatin C concentration in liver. Liver cystatin C concentration decreased in the HA-1 hepatoma group and treatment with Ukrain or carboxymethylated beta-1, 3-glucan (CMG) increased this index in both groups. Spleen cystatin C concentrations decreased about 5-fold in LS lymphosarcoma compared with controls and combined treatment with cyclophosphane plus Ukrain restored the index to the normal value. We can conclude that both murine tumors studied were characterized by low cystatin C concentrations in tumor tissues and decreased cystatin C concentrations (to a lesser degree) were also observed in liver and spleen as a result of the "toxic" effect of tumor bearing. Effective treatment in all cases (especially with Ukrain or a combination of cyclophosphane plus Ukrain) induced a significant increase in cystatin C. Obviously, the decrease in cystatin C concentration predominantly in tumor tissue was connected with tumor development and restoration of cystatin C level may be used as a marker of efficacy of antitumor therapy.

Alkaloids↗