TRAIL receptors in the serum of patients with B-cell chronic lymphocytic leukemia.

Great importance in the course of chronic B-cell lymphocytic leukemia (B-CLL) has been ascribed to cytokines belonging to the superfamily of the tumor necrosis factor (TNF), including TRAIL (TNF-related apoptosis inducing ligand) and its specific receptors: TRAIL receptor 1 (TRAIL-R1), TRAIL receptor 2 (TRAIL-R2), TRAIL receptor 3 (TRAIL-R3), TRAIL receptor 4 (TRAIL-R4) and osteoprotegerin (OPG). Both the molecule and the receptors may occur in membrane and soluble forms, except for OPG which has only a soluble form. The aim of the study was to assess the levels of sTRAIL molecule and soluble TRAIL receptors - sTRAIL-R2 and OPG in the serum of patients with B-CLL. The findings revealed reduced concentrations of sTRAIL both before and after treatment and elevated levels of sTRAIL-R2 and OPG in patients before treatment. After treatment with CC (2CdA/Cladrybin and Cyklofosfamid) and FC (Fludarabin and Cyklofosfamid) we observed an increase in sTRAIL and a decrease in sTRAIL-R2. OPG levels were found to increase after treatment with CHOP (Vincristini, Cyklofosfamid, Adriamycin and Prednisol) and they decreased after administration of Leukeran (Chlorambucyl) and CMC (2CdA/Cladrybin, Mitoxanton and Cyklofosfamid). The relationships between TRAIL and its natural regulators in the serum of BCLL patients prior to treatment may impair apoptosis of leukemic B cells. Changes in these relationships after treatment with CC and FC seem to promote enhancement of apoptosis in these cells.

Reactive oxygen and nitrogen species in the course of B-CLL.

PURPOSE: The study objective was to investigate the production of NO, cGMP and superoxide anion radical by neutrophils, and to examine alterations in serum or plasma total nitric oxide, MDA and cGMP levels in B-CLL patients. MATERIAL AND METHODS: PMNs were isolated from 20 patients with B-CLL. Total nitrite was measured in cell supernatants and serum by Griess method. The generation of superoxide anion radical by cells was estimated using cytochrom-c reduction test. The cGMP level in cell supernatants and plasma was assessed by ELISA kit whereas serum MDA level using a spectrophotometric assay by Guege and Aus. RESULTS: The PMNs in B-CLL patients were characterised by impaired NO generation and enhanced cGMP production. Contrary to the control group, no significant effect was found of rhlL-15 and rhIL-18 on the release of these mediators by PMNs. Superoxide anion radical release by PMNs was decrease. Serum MDA and plasma cGMP levels were elevated in B-CLL patients as compared to the controls. CONCLUSIONS: The reduced production of nitric oxide and superoxide anion radicals by PMNs in B-CLL may impair the cytotoxic effect of neutrophils on leukaemic B cells. Low secretion of nitric oxide by PMNs and high levels of cGMP in PMN supernatants suggest that activation of guanyl cyclase (sGC) in these patients may occur in the presence of agents other than nitric oxide. Moreover, the findings indicate the enhancement of lipid peroxidation with the progression of the neoplastic process in B-CLL patients.

Soluble form of TRAIL, Fas and FasL in the serum of patients with B-CLL.

PURPOSE: Although many studies demonstrated expression of TNF family members in the course of B-CLL, there is a little known about relationships between soluble forms of these proteins. Furthermore, there is no study reported on effects of used therapy on this relation. The present study was designed to asses the relationships between the serum concentrations of sFas, sFasL and sTRAIL in patients with B-CLL regarding their correlation with clinical stage and used therapy. MATERIAL AND METHODS: We studied 40 patients with B-cell chronic lymphocytic leukemia (B-CLL) at diagnosis, before treatment and four weeks after therapy. To measure sFas, sFasL and sTRAIL levels in serum commercially available ELISA kits were used. RESULTS: We found increased concentrations of sFas in sera of all patients with B-CLL before treatment in comparison to the control group. There were no significant differences in concentrations of sFasL and sTRAIL between patients and control group. Increased sFasL concentrations after FC and CC therapy as well as decreased concentrations after 2CdA therapy in comparison to values before treatment were found. The concentrations of sTRAIL after FC and CC therapy were higher than those in patients before treatment. CONCLUSIONS: Results obtained suggest that relationship between sFas, sFasL and sTRAIL in sera of patients with B-CLL before treatment may facilitate the growth B leukemic cells. Changes in these relations after therapy with FC and CC can make a contribution to inhibit B cells growth on the apoptosis way in this patient group.

Cytokine and adhesion molecule concentrations in blood of patients with B-cell chronic lymphocytic leukaemia with regard to disease progression.

PURPOSE: To examine concentrations of IL-8, E-selectin and VCAM-1 in blood plasma, culture supernatant and isolated broken lymphocytes in patients with chronic lymphocytic leukaemia (CLL), at I and III stage of the disease according to Rai's classification and in healthy individuals constituting controls. Two types of lymphocyte cultures were carried out--nonstimulated and stimulated with mitogen. MATERIAL AND METHODS: A concentration assay of substances mentioned above was made using ready immuno-enzymatic sets of the ELISA type. RESULTS: In all cases, plasma concentrations of IL-8, E-selectin and VCAM-1 were the highest in III stage of CLL and moderately increased in I stage comparing to control. The concentrations of IL-8 in culture supernatants and in broken lymphocytes and concentration of VCAM-1 in lymphocytes were increased in both stages of CLL. In contrast concentrations of E-selectin were decreased in lymphocytes in both types of culture. Significant decrease of E-selectin and VCAM-1 concentrations were observed in supernatants of nonstimulated cultures. CONCLUSION: Significant increase of E-selectin, IL-8 and VCAM-1 concentration in blood plasma may support higher activity and suggest the higher ability of leukaemic lymphocytes to migration. Increased IL-8 concentration in isolated, broken, stimulated lymphocytes may be a characteristic feature of the biochemical processes of leukaemic lymphocytes. The lowest values of E-selectin and VCAM-1 concentrations in culture supernatants and broken lymphocytes may suggest their degradation during in culture.

[Some adhesion molecules in blood of patients with chronic B-cell lymphocytic leukemia]. / Niektóre czasteczki adhezyjne we krwi chorych na przewlekla bialaczke limfatyczna B-komórkowa.

Adhesion molecules actively participate in all stages of leukocyte migration, directly or indirectly by means of appropriate ligands. Therefore the aim of study was the determination of concentrations of L-selectin and ICAM-1 in cell culture supernatante, broken lymphocyte and plasma. The measurement of cell adhesion molecules (CA) concentrations were performed by means of immunoenzymatic kits of ELISA type in the patients with chronic lymphocytic leukaemia in the clinicals stages I and III. The levels of L-selectin were increased in cell culture supernatante but in the plasma concentrations of L-selectin were decreased. The behaviour of concentrations of studied substances in the broken lymphocytes was differently. It is possible that these investigations may appear useful in the future as an additional diagnostic indecks.

[Diagnostic value of some cytokines levels in chronic myelogenous leukemia]. / Wartosc diagnostyczna aktywnosci stezen cytokin w przewleklej bialaczce szpikowej.

Some cytokines play an important role in aetiology and pathogenesis of leukaemia. Majority of data available in the literature relates to a single cytokine in the cell culture in vitro. In patients with chronic myelogenous leukaemia several different cytokines are probably active. Therefore, this study aimed to determine the concentrations of interleukin-1 beta, G-CSF, L-selectin in leukaemia cell culture supernatant, broken granulocytes and plasma in the course of disease exacerbation and remission. Cytokines have been assayed with available immunoenzymatic kits of ELISA type. IL-1 beta, G-CSF and L-selectin levels have been increased in cell supernatant but IL-1 beta level has been decreased in non-stimulated broken granulocytes. G-CSF levels have been low both in stimulated and non-stimulated granulocytes. In comparison to control the lowered levels of G-CSF and L-selectin have been observed in blood plasma of patients with CML. Different levels of assayed cytokines and adhesion molecule may suggest their contribution to leukaemia cells proliferation regulation.

[The role of some cytokines in the etiopathogenesis of leukemia]. / Rola niektórych cytokin w etiopatogenezie bialaczek.

Some cytokines play important role in etiology and pathogenesis of leukaemia. Most of them more stimulate than inhibit the proliferation of leukaemia cells.

[An attempt to clarify the etiopathogenesis of chronic lymphatic B-cell leukemia]. / Próby wyjasnienia etiopatogenezy przewleklej bialaczki limfatycznej B-komórkowej.

The paper presents current opinions about aetiology and pathogenesis of chronic lymphatic B-cell leukaemia.

[Cytokines in acute myeloid leukemia]. / Cytokiny w ostrej bialaczce szpikowej.

The cytokines belong to the group of main factors regulating of leukaemia cell proliferation. Most of information comprised in the literature concern the behaviour of single cytokines in the cell culture in vitro. In the organism of leukaemia patient many different cytokines, adhesion molecules, growth factors and other substances probably act in the same time. Therefore the aim of study was the determination of plasma concentrations of interleukin 1B, 3, 4, 6, 8, G-CSF and P-selection in 26 patients with acute myeloblastic leukaemia-aml, among them 14 patient in the course of exacerbation-aml-e and 12 being in the remission-aml-r, classified as type M1 and M2 according to the FAB classification. Control group consisted of 15 healthy volunteers. The cytokine measurements were performed by means of immunoradiometric, immunoenzymatic and radioimmunologic kits. In the patients with aml-e significant increase of plasma concentrations of IL-1B, IL-3, IL-6, G-CSF, P-selectin and essential decrease of IL-4 was found. Significant decrease of IL-4 and P-selecting concentrations in the patients with aml-r and lack of changes in IL-8 concentrations in the both groups of patients was demonstrated. The observed differences of concentrations may additionally confirm the role of studied cytokines and P-selectin in the regulation of leukaemia cell proliferation.

[The role of some cytokines in the physiology of proliferation of hematopoietic cells]. / Rola niektórych cytokin w fizjologii proliferacji komórek ukladu krwiotwórczego.

Cytokines are of great importance in the regulation of proliferation of haematopoietic system cells. Most of known cytokines stimulate the proliferation of cells of granulocyte-macrophage, monocyte, and lymphocyte system. Some of them stimulate the proliferation of cells from erythrocyte, eosinophil and megakaryocyte systems and proliferation of B and T lymphocytes.

[Cytokines in certain proliferative diseases of the hematopoietic system]. / Cytokiny w niektórych chorobach rozrostowych ukladu krwiotwórczego.

Some cytokines playing a great role in the proliferation of neoplastic haematopoietic system cells were described. Most of cytokines stimulate the cell proliferation in non-lymphoblastic leukemia, less of them act in lymphocytic leukemia and least in the other proliferative diseases of haematopoietic system.

[Examination of interleukin levels and growth factor from blood platelets in leukemia]. / Badania stezen interleukin oraz czynnika wzrostowego z plytek krwi w bialaczkach.

Plasma concentrations of interleukines 1, 3, 6, 8 and platelet derived growth factor (PDGF) were estimated in 45 patients with leukaemias. Among patients were 12 with acute myeloblastic leukaemia-AML (type M1 according to FAB classification), 9 with chronic granulocytic leukaemia-CGL, 10 with blastic crisis of CGL (CGL-BC) and 14 with chronic lymphocytic leukaemia-CLL (in 1 and 2 stage according to Rai classification). Additionally the concentration of IL-3 was measured in 10 patients with exacerbation of CLL. Control group consisted of 12 health volunteers. The concentrations of interleukines and PDGF were determined by means of radioimmunoassay or immunoradiometric assay. In the patients with AML, CGL-BC and CLL significant increase of concentrations of IL-1B, IL-6 were found. The patients suffers from CGL and CGL-BC had increase concentrations of IL-3, but patients with CLL-interleukin 8. The concentrations of PDGF were significantly decreased in the patients with AML, CGL-BC, and CGL. The differences of concentrations of studied interleukines can confirm their great significance in proliferation of leukaemic cells. The decrease of concentrations of PDGF in myelocytic leukaemias may reflect thrombopoietic disturbances in these illnesses.

Clinical investigations on long-term activation of fibrinolysis by anabolic steroids.

The influence of anabolic steroids plus phenformin on the course of disease was studied in patients suffering from occlusive vascular diseases. In arteriosclerosis obliterans of the lower limbs the combined therapy led to a higher percentage of improvement than the control group showed. In coronary heart disease there was also a beneficial effect of this treatment. The drugs were found to exert beneficial clinical effects especially in patients with thrombophlebitis migrans and superficial thrombophlebitis. From the results of this study it is concluded that this therapy may be of clinical value in the treatment of patients with occlusive vascular diseases.