Antiapoptotic proteins mcl-1 and bcl-2 as well as growth factors fgf and vegf influence survival of peripheral blood and bone marrow chronic lymphocytic leukemia cells

© 2020, University of Kragujevac, Faculty of Science. All rights reserved. Apoptosis inhibition in chronic lymphocytic leukemia (CLL) is one of the most important mechanism in the disease onset, progression and therapy response and is dependent of interaction with different microenvironments. Aim of our paper is to determine expression of antiapop-toic proteins mcl-1 and bcl-2 in CLL cells isolated from two different compartments (peripheral blood and bone marrow) and its relation to percent of apoptotic cells and concentration of growth factors (FGF and VEGF). Our results showed that peripheral blood CLL lymphocytes have lower apoptotic rate then those isolated from bone marrow, though bone marrow CLL lymphocytes express higher levels of antipoptotic proteins bcl-2 and mcl-1. In bone marrow FGF concentration is 10-fold higher then in patients plasma but has an limited impact on mcl-1 expression. In contrary, VEGF concentration is higher in peripheral blood and corelate with percent of apoptotic cells and mcl-1 expression in this compartment. CLL cells derived from two different microenvironmets acts differently when tested for apoptosis „ex vivo“. In peripheral blood apoptosis is strongly connected with expression of antiapoptoic proteins (mcl-1 and bcl-2) and growth factors, but not in bone marrow

Association between risk factors, basal viral load, virus genotype and the degree of liver fibrosis with the response to the therapy in patients with chronic hepatitis C virus infection

© 2015, Institut za Vojnomedicinske Naucne Informacije/Documentaciju. All rights reserved. Background/Aim. Hepatitis C is an important sociomedical problem worldwide due to frequent progression to chronic dis-ease, occurrence of liver cirrhosis and hepatocellular carcinoma. Standard pegylated interferon alfa 2a plus ribavirin therapy results in resolution of infection only in 50% of patients. The aim of this study was to determine the association of various factors with re-sponse to the therapy in patients with chronic heptitis C virus (HCV) infection. Age and sex of patients, inoculation risk factors, histopathological changes in the liver, viral load and HCV geno-type were analyzed. Methods. The study included a group of 121 patients with chronic HCV infection. The treatment was carried out 24 weeks for virus genotype 2 and 3, and 48 weeks for geno-type 1 and 4. The degree of histopathological changes in the liver was determined by hematoxylin and eosin staining, whereas polimerase chain reaction was used for HCV genotyping. Results. In the group of non-responding patients genotype 1 was repre-sented with 100%, while in the other groups, although predomi-nantly present, its percentage was lower. Unresponsiveness to therapy and relapse of disease were associated with higher viral load and advanced fibrosis. Intravenous use of psychoactive sub-stances, as a risk factor, was present in a high percentage in the group of patients with sustained response, while blood transfusion and dialysis were leading risk factors in the group of relapse re-sponders and non-responders. Conclusion. The results of our study showed that the treatment outcome of chronic HCV infec-tion was associated with baseline HCV ribonucleic acid, HCV genotype, route of infection and the degree of histopathological changes in the liver

Ligustrum vulgare leaves and fruit extracts induce apoptosis of human leukemia cells

Background and purpose: Cytotoxic effects of Ligustrum vulgare leaves on HeLa cervical tumor cells suggested that Ligustrum vulgare extracts should be investigated as potential anticancer agents. Therefore, we examined a potential antileukemic activity of methanolic extracts of Ligustrum vulgare leaves and fruit extracts on two types of leukemia cells, MOLT-4 and JVM-13, lymphocytes isolated from the blood of 33 chronic lymphocytic leukemia (CLL) patients and on mononuclear leukocytes isolated from the blood of 18 healthy individuals.Material and methods: The cytotoxicity of examined extracts was measured by MTT assay and LDH activity test. The antiapoptotic potential of tested extracts was measured by Annexin V/7AAD flowcytometric assay.Results: The results showed that both extracts exhibited a moderate cytotoxic effect on all three types of leukemia cells. The Ligustrum vulgare leaf extract was the most effective on MOLT-4 cells, the fruit extract on JVM-13 cells and both extracts were equally effective on CLL cells. In addition, none of the tested extracts was toxic to healthy mononuclear cells. Both extracts acted by inducing apoptosis of leukemic cells.Conclusion: Ligustrum vulgare extracts exhibit significant antileukemic potential and should be further investigated

Effects of host defense peptides B2RP, Brevinin-2GU, D-Lys-Temporin, Lys-XT-7 and D-Lys-Ascaphin-8 on peripheral blood mononuclear cells: Preliminary study

Background and purpose: Host defense peptides have considerable therapeutic potential. One of the limitations for their therapeutic use is insufficient selectivity of some peptides, i.e. toxicity for eukaryotic cells. In this study, we have investigated effect of two naturally occurring and three analogs of frog skin-derived peptides on viability/proliferation of resting peripheral blood mononuclear cells and activated lymphocytes.Materials and Methods: Effect of tested peptides was assessed using MTT colorimetric assay. Concanavalin A was used as lymphocyte mitogen.Results: Brevinin-2GU induced cell death only in the highest tested concentration, whereas other peptides were not cytotoxic to resting peripheral blood mononuclear cells. Moreover, high concentrations of B2RP, D-Lys-Ascaphin-8  and Lys-XT-7 induced cell proliferation and this effect was more prominent in lymphocytes (pConclusions: Tested peptides (with exception of Brevinin-2GU) didn’t show cytotoxicity toward peripheral blood mononuclear cells. Moreover, they have potential to modulate immune response by inducing proliferation of resting peripheral blood mononuclear cells and limiting proliferative response to the activation stimulus. Regarding their potent antimicrobial and low hemolytic activity this makes them good candidates for therapeutic use.Key words: host defence peptides; cytotoxicity; immunomodulation </p

Isolated myeloid sarcoma of the neck and chest: differential diagnosis and therapeutic approach

In this article, we present the case of a 57-yearold man with cervical and mediastinal tumor mass, normal blood count as well as virusological status. Cervical tumor tissue biopsy revealed cells positive for CD34, CD13, LCA, CD33, and CD163 but negative for T-cell and B-cell markers, NK-cell markers, plasmacytic markers and anaplastic large cell lymphoma markers. These features were consistent with myeloid sarcoma of the neck with involvement of the mediastinum. We discussed differential diagnosis and therapy of isolated myeloid sarcoma and suggest that clinical presentation, cell morphology, complete immunophenotype, and specific genotypic lesions in some cases, must be evaluated

Isolated myeloid sarcoma of the neck and chest: Differential diagnosis and therapeutic approach

© 2015 Predrag Djurdjevic, Danijela Jovanovic, Darko Antic. In this article, we present the case of a 57-yearold man with cervical and mediastinal tumor mass, normal blood count as well as virusological status. Cervical tumor tissue biopsy revealed cells positive for CD34, CD13, LCA, CD33, and CD163 but negative for T-cell and B-cell markers, NK-cell markers, plasmacytic markers and anaplastic large cell lymphoma markers. These features were consistent with myeloid sarcoma of the neck with involvement of the mediastinum. We discussed differential diagnosis and therapy of isolated myeloid sarcoma and suggest that clinical presentation, cell morphology, complete immunophenotype, and specific genotypic lesions in some cases, must be evaluated

Antiapoptotic Proteins mcl-1 and bcl-2 as well as Growth Factors FGF and VEGF Influence Survival of Peripheral Blood and Bone Marrow Chronic Lymphocytic Leukemia Cells

Apoptosis inhibition in chronic lymphocytic leukemia (CLL) is one of the most important mechanism in the disease onset, progression and therapy response and is dependent of interaction with different microenvironments

Hepatitis C Therapy – Related Haematological Side Effects are Associated with Treatment Outcome / Hematološka Neželjena Dejstva Terapije Hepatitisa C Su Povezana Sa Ishodom Lecenja

Treatment of patients suffering from chronic hepatitis C with standard pegylated interferon alpha 2a plus ribavirin has limited efficacy. Therapy outcome is dependent on several factors of both the host and virus, including age, sex, stage of fibrosis, viral genotype, viral load, and occurrence of haematological adverse events during chronic hepatitis C treatment. The aim of this study was to determine the relationship between the viral and host factors and the haematological side effects of therapy with sustained virological response