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Biomedical subjects

A Dabrowska

Publications and source records attributed to A Dabrowska.

At least 37 records · Page 2Linked to original sources
PubMed1998

Granulocyte colony-stimulating factor demonstrates antitumor activity in melanoma model in mice.

Granulocyte colony-stimulating factor (G-CSF) was found to exert antitumor activity against murine MmB16 melanoma when administered intratumorally. However, subcutaneous administration of this cytokine at a site distant from the growing tumor did not show any antitumor effects. G-CSF did not influence the proliferative activity of MmB16 in vitro. Intraperitoneal administration of G-CSF resulted in decreased secretion of nitric oxide (NO) by peritoneal macrophages and their decreased tumoricidal activity against MmB16.

Animals↗
PubMed1997

Antitumor effects of the combination immunotherapy with interleukin-12 and tumor necrosis factor alpha in mice.

There is strong evidence that antitumor activity of interleukin-12 (IL-12) in vivo is mediated, in part, through interferon (IFN gamma) produced by IL-12-stimulated natural killer and T cells. Since IFN gamma and tumor necrosis factor alpha (TNF alpha) have been reported to synergize in antitumor effects in a number of models, we decided to examine whether the combined treatment with recombinant mouse IL-12 and recombinant human TNF alpha would produce similar effects. The efficacy of the combined IL-12/TNF alpha immunotherapy was evaluated in three tumor models in mice: B16F10 melanoma, Lewis lung (LL/2) carcinoma and L1 sarcoma. Intratumoral daily injections of 1 microgram IL-12 in combination with 5 micrograms TNF alpha into B16F10-melanoma-bearing mice resulted in a significant retardation of the tumor growth as compared with that in controls and in mice treated with either cytokine alone. Similar effects were obtained using 0.1 microgram IL-12 and 5 micrograms TNF alpha in LL/2 carcinoma and L1 sarcoma models. Antitumor activity against L1 sarcoma was still preserved when TNF alpha at a low dose (1 microgram) was combined with 0.1 microgram IL-12 and applied for a prolonged time. Potentiation of antitumor effects, which was observed in IL-12/TNF alpha-based immunotherapy, could result from at least three different mechanisms, partly related to stimulation of IFN gamma and TNF alpha production in treated mice: (a) direct cytostatic/cytotoxic effects on tumor cells, (b) induction of antitumor activity of macrophages, and (c) inhibition of blood vessel formation in the tumor. Our studies demonstrate that combination tumor immunotherapy with IL-12 and TNF alpha may be more effective than single-cytokine treatment, and suggest possible mechanisms by which IL-12 and TNF alpha may exert potentiated therapeutic effects against locally growing tumors.

Animals↗
PubMed1997

[Erythrocyte pyruvate kinase--an enzyme that may have an influence on oxygen transport to tissues].

Hemoglobin, the critical protein in the delivery of oxygen to mammalian tissues, is poorly adapted to that function. This awkward situation is remedied by the presence in the red cell of 5 to 7 mM 2.3 DPG, which binds to Hb competitively with oxygen and reduces oxygen affinity. How the levels of 2.3 DPG in the red cell are regulated is an important question that has not yet been fully answered. The best established correlation with 2.3 DPG concentration in red cells is the activity of the enzyme pyruvate kinase. Inverse relationship between 2.3 DPG content and pyruvate kinase activity is the result of two conditions within the erythrocyte. The metabolites between FBP and PEP are in a state of quasi equilibrium because the activity of pyruvate kinase is so much lower than the activities of other enzymes in the pathway. Furthermore, pyruvate kinase operates, in vivo at a PEP concentration well below the Km concentration. In consequence, an increase in the glycolytic rate or inhibition of pyruvate kinase causes an increase in PEP concentration. Increases in PEP levels lead to increases in the levels of 2.3 DPG, and hence to increase in the level of 2.3 DPG via the 2.3 DPG synthase reaction. This relationship is demonstrated by the frequent occurrence of elevated levels of 2.3 DPG in pyruvate kinase deficient erythrocytes and by the decreased levels of 2.3 DPG and PEP which are observed in erythrocytes containing a pyruvate kinase with abnormally high activity at low PEP levels. It is thus clear that control of pyruvate kinase activity is a means to the control of oxygen delivery by the erythrocyte. It remains to be discovered whether any of the observed variations in human PK activity are due to reversible posttranslational modification and whether the potential for control of oxygen delivery via changes in pyruvate kinase activity is made use of the normal human adult. The availability of human full length of cDNA for PK should accelerate our understanding of he structure-function relationships of PK deficiency and enhance the possibility of gene therapy for seriously affected PK patients.

Adult↗
PubMed1995

Interaction of bovine heart pyruvate kinase with phospholipids.

The interaction between bovine heart pyruvate kinase and liposomes was investigated for various phospholipids as function of pH, and salt concentration using steady-state kinetics and ultracentrifugation. Liposomes made from erythrocyte total lipid fraction and individual phospholipids were used. Pyruvate kinase specific activity increases upon the interaction with the phospholipids. The activation is specifically sensitive to presence of phosphatidylserine in liposomes. L-serine, and phospho-L-serine which are main components of phosphatidylserine head group show also some activation effect. Efficient adsorption of pyruvate kinase to phosphatidylserine liposomes occurs in the pH range 6.0-8.0 and at low ionic strength. Interaction with phosphatidylserine liposomes results in the change of Vmax and Km values for phospho enol pyruvate without marked effect on Km value for ADP, and Hill coefficients for both substrates. The interaction does not seem to influence the cooperativity between binding sites.

Animals↗
PubMed1990

Limited proteolysis of bovine muscle and heart lactate dehydrogenase is inhibited by phospholipid liposome interaction.

Limited proteolysis of phospholipid complexes of heart and muscle bovine lactate dehydrogenase by trypsin and chymotrypsin has been studied under nondenaturing condition at pH 7.5. Chymotrypsin cleaves the polypeptide chain of heart and muscle lactate dehydrogenase into two principal fragments and LDH subunits were protected by lipids towards the proteinase attack. Enzymatic activity of heart and muscle lactate dehydrogenase was abolished by limited proteolytic cleavage. In complexes, both isoenzymes were protected against proteinases attack by lipids.

Animals↗
PubMed1989

Interaction of bovine skeletal muscle lactate dehydrogenase with liposomes. Comparison with the data for the heart enzyme.

The effects of pH, salt concentration and the presence of oxidized and reduced forms of coenzyme on the interaction of skeletal muscle lactate dehydrogenase with the liposomes derived from the total fraction of bovine erythrocyte lipids were investigated by ultracentrifugation and were compared with those results obtained using the heart-rate isoenzyme which we have previously studied. Liposomes are good adsorptive systems for both types of isoenzyme. In the presence of erythrocyte lipid liposomes, bovine muscle and heart lactate dehydrogenases form two kinds of complex: lactate dehydrogenase adsorbed to liposomes and soluble lactate dehydrogenase-phospholipid complexes. Soluble protein-phospholipid complexes reveal different dependences of their stabilities on pH values and it seems that the nature of the binding site in either isozyme is different. In addition, absorption of the isoenzymes on the liposomes also reveals in difference in the effects of NAD and NADH. While the presence of NAD dissociates LDH-H4 from the liposomes and NADH does not influence its adsorption, NAD promotes the binding of LDH-M4, and NADH favors the dissociation.

Animals↗
PubMed1989

Quality of survival of patients with brain gliomas treated with postoperative CCNU and radiation therapy.

This prospective randomized clinical trial compared the effectiveness of combined treatment with CCNU and radiation therapy to the use of radiation therapy alone for the postoperative management of supratentorial brain gliomas (67% anaplastic) in 198 patients. The results were evaluated with the aid of a specially developed weighted neuropsychological test battery providing single-value estimation of "life quality" of patients, as well as with a clinical performance scale. Based on these methods, it was established that patients improved within 6 months following therapy. This improvement was maintained in surviving patients during the 2-year follow-up period. The patients led a relatively normal life, but when their condition deteriorated their decline was rapid. The median survival time of patients treated with radiotherapy did not differ significantly from that of patients receiving chemotherapy in addition. Nor did the analysis of life quality and of changes in clinical performance show any benefit in supplementing surgery and radiation therapy with CCNU chemotherapy at the dosage used.

Adolescent↗
PubMed1986

Interaction of bovine heart lactate dehydrogenase with erythrocyte lipids.

The interaction between bovine heart lactate dehydrogenase and erythrocyte lipid suspension as a function of pH, NAD, NADH, lipid and salt concentration was studied by ultracentrifugation. In the presence of erythrocyte lipid liposomes the enzyme forms two kinds of complex: lactate dehydrogenase adsorbed to liposomes and soluble lactate dehydrogenase-phospholipid complexes. The two complexes reveal different dependence of their stability on pH values. Lactate dehydrogenase decreases its specific activity when it binds to the phospholipid molecules. Efficient adsorption of lactate dehydrogenase to liposomes occurs in their pH range 6.0-8.0 and at low ionic strength. The adsorption is diminished in the presence of NAD+ but it is not influenced by NADH. Possible mechanisms of the interaction and implications for the function in vivo are discussed.

Adsorption↗
PubMed1978

Purification, crystallization and properties of triosephosphate isomerase from human skeletal muscle.

1. Triosephosphate isomerase (D-glyceraldehyde-3-phosphate ketoisomerase, EC 5.3.1.1) from human skeletal muscle was purified to homogeneity and crystallized. The crystalline enzyme preparation was resolved on polyacrylamide-gel electrophoresis into three isoenzymes. 2. The molecular weight of the enzyme estimated by gel filtration method was found to be 57,400 +/- 3000. Molecular weight determination under dissociation conditions indicated a dimeric subunit structure of the enzyme. 3. The apparent Km for D-glyceraldehyde-3-phosphate as substrate is 0.34 mM, and for dihydroxyacetone phosphate, 0.61 mM. Vmax of the reaction is, respectively, 7200 and 660 units/mg protein at 25 degrees C and pH 7.5. 4. Molecular and kinetic properties of triosephosphate isomerase from human skeletal muscle are very similar to those of rabbit muscle enzyme.

Carbohydrate Epimerases↗
PubMedDate not supplied

Potentiated antitumor effects of interleukin 12 and matrix metalloproteinase inhibitor batimastat against B16F10 melanoma in mice.

The application of antiangiogenic agents in cancer therapy has been studied extensively. Combination of agents with antiangiogenic properties could possibly enhance antitumor effects. Interleukin 12 is a cytokine with potent antitumor activity mediated also via antiangiogenic mechanisms. These effects are attributed to IFN-gamma production stimulated by IL-12. Since IFN-gamma has been reported to augment antitumor effects when combined with one of the metalloproteinase inhibitors--batimastat (BB-94), we have examined a combined treatment with IL-12 and BB-94 in a murine melanoma model. The administration of both agents showed potentiated antitumor activity. Furthermore, we have shown in a tumor-induced angiogenesis model that the combined application of IL-12 and batimastat inhibits the formation of new blood vessels to a greater extent than either agent alone. Our observations show that antiangiogenic effects are at least partly responsible for the enhanced antitumor effects of the combined treatment with IL-12 and BB-94.

Adjuvants, Immunologic↗