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1

Effect of granulocyte-macrophage colony stimulating growth factor on interferon and tumor necrosis factor production in whole blood cell cultures of patients with acute myelogenous leukemia

100%
Kaminska T., Hus I., Dmoszynska A., Kandefer-Szerszen M.
Archivum Immunologiae et Therapiae Experimentalis
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2001
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vol. 49
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issue 2 suppl.
83-88
EN
The effect of recombinant human granulocyte-macrophage colony-stimulating growth factor (rHuGM-CSF) treatement on in vitro interferon (IFN) and tumor necrosis factor (TNF) production in peripheral blood cells of 46 patients with acute myelogenous leukemia (AML) was examined. GM-CSF significant enhanced virus-induced IFN- production in blood cells (containing 70% of blasts) of 28 patients with M4-M5 AML according to the French-American-British (FAB) classification and also phytohemagglutinin (PHA)-induced IFN- production in blood cells (containing 68% of blasts) of 18 patients with AML M0-M3 type. In control blood cells (25 healthy persons) GM-CSF enhanced PHA-induced IFN- but did not influence IFN- production. In the presence of GM-CSF, TNF- titers induced with lipopolysaccharide were also higher in control blood cells but not in cells of patients with M0-M3 or M4-M5 type of AML. The significance of GM-CSF-enhanced IFN- and IFN- production in antimicrobial and antileukemic immune reactions which can develop during GM-CSF therapy is discussed.
2

Cytokine production in whole blood cell cultures of patients with B-lineage acute lymphoblastic leukemia. The influence of granulocyte-macrophage colony stimulating factor

100%
Kaminska T., Hus I., Dmoszynska A., Kandefer-Szerszen M.
Archivum Immunologiae et Therapiae Experimentalis
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2001
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vol. 49
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issue 1
71-80
EN
We investigated the levels of 6 different cytokines in the sera of 10 newly diagnosed patients with B-cell lineage acute lymphoblastic leukemia (ALL) and detected a significant increase in IL-6 and IFN- serum levels in comparison to that of healthy controls. Whole blood cell cultures of 10 ALL patients and 20 control individuals were induced with classical cytokine inducers, such as virus, PHA and LPS, and their ability to produce 9 different cytokines was compared. Blood cells of ALL patients produced significantly less IL-1, IL-1, IL-10 and TNF- than control cells and not significanly lower levels of IL-6, but comparable with control levels of IL-2, IL-4. rHuGM-CSF added to cell cultures 24 hr before induction significantly enhanced the production of IL-1, IL-1 and TNF- in controls, but only IL-1 and IL-1 in the blood cell cultures of patients with ALL. GM-CSF did not significantly influence the production of IFN-, IFN-, IL-2, IL-4 and IL-10 in the control cells and the cells of ALL patients. The patients examined differed not only in the expression of CD10 and CD34 antigens on blast cells, but also in the reaction to GM-CSF treatment, which was found as very high standard deviation values. We suppose that these differences can partially explain the different effects of GM-CSF when used to ameliorate neutropenia of ALL patients after chemotherapy and to reduce the incidence of microbial infections.
3

Abnormal cytokine production by bone marrow stromal cells of multiple myeloma patients in response to RPMI8226 myeloma cells

100%
Zdzisinska B., Bojarska-Junak A., Dmoszynska A., Kandefer-Szerszen M.
Archivum Immunologiae et Therapiae Experimentalis
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2008
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vol. 56
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issue 3
207-221
EN
Introduction Recent studies indicate that bone marrow stromal cells (BMSCs) derived from patients with multiple myeloma (MM) differ from those of healthy donors in their expression of extracellular matrix compounds and in cytokine production. It is not known whether these abnormalities are primary or are acquired by BMSCs on contact with MM cells. Materials and Methods: Interleukin (IL)-6, IL-11, IL-10, and tumor necrosis factor (TNF)-alpha production by CD166+ mesenchymal BMSCs and the CD38+/CD138+ RPMI8226 myeloma cell line cultivated in vitro in monocultures or co-cultivated under cell-to-cell contact or non-contact conditions in the presence of a tissue culture insert were measured. Intracellular cytokines were measured by flow cytometry analysis as the percentage of cytokine-producing cells or by mean fluorescence intensity as the level of cytokine expression in cells. Additionally, ELISA was used to measure IL-6, soluble IL-6 receptor (sIL-6R), IL-11, IL-10, TNF- alpha, B-cell-activating factor of the TNF family (BAFF), hepatocyte growth factor (HGF), and osteopontin (OPN) production in the supernatants of the cultures and co-cultures. Results A higher ability of the BMSCs of MM patients than in controls was detected to produce IL-6, IL-10, TNF- alpha, OPN, and especially HGF and BAFF in response to the RPMI8226 cells. Moreover, the BMSCs of the MM patients significantly enhanced the production of sIL-6R by the RPMI8226 cells. Discussion Cytokines over-expressed by BMSCs of MM patients can function as growth factors for myeloma cells (IL-6, IL-10, HGF), migration stimulatory factors for tumor plasma cells (TNF-alpha, HGF), adhesion stimulatory factors (HGF, BAFF and OPN), stimulators of osteoclastogenesis (IL-6, TNF-alpha), and angiogenic factors (TNF-alpha). The results of this experiment strongly suggest that the BMSCs from MM patients differed in spontaneous and myeloma cell-induced production of cytokines, especially of HGF and BAFF, and these abnormalities were both primary and acquired by the BMSCs on contact with the MM cells. This in turn suggests the presence of an undefined, autocrine stimulation pathway resulting in a prolonged production of cytokines even in long-term cultures in vitro and in vivo. These abnormalities might provide optimal conditions for the proliferation and differentiation of residual tumor cells or their precursors in the affected bone marrow.
4

Matrix metalloproteinase and cytokine production by bone marrow adherent cells from multiple myeloma patients

100%
Zdzisinska B., Walter-Croneck A., Dmoszynska A., Kandefer-Szerszen M.
Archivum Immunologiae et Therapiae Experimentalis
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2006
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vol. 54
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issue 4
289-296
EN
Introduction: Cultures of bone marrow stromal cells derived from the bone marrow of multiple myeloma (MM) patients were shown to exhibit several abnormalities compared with control cultures from healthy subjects. The aim of the study was to examine whether cultures of bone marrow adherent cells, at low passage level, exhibit differences in matrix metalloproteinases (MMPs) and cytokine production compared with cultures from normal donors. Materials and Methods: MMP production was evaluated by gel zymography and by ELISA in supernatants of serum-free cultures of bone marrow adherent cells derived from 20 MM patients and 23 healthy controls. Spontaneous and lipopolysaccharide (LPS)- or Newcastle disease virus (NDV)-induced cytokine release was assessed in the supernatants of the cultures by the ELISA method. Results: Both cultures produced MMP-1, -2, -3, and -9 under serum-free conditions; however, the levels of MMP-1 and MMP-2 were significantly higher in cultures derived from MM patients, while MMP-3 was significantly higher in control cultures. The level of MMP-9 was comparable in the cultures derived from MM patients and controls. All cultures produced interleukin (IL)-10 and IL-11 spontaneously, but after LPS or NDV induction the levels of IL-10, IL-11, interferon , and tumor necrosis factor , were significantly higher in the cultures derived from MM patients than in control cultures. Conclusions: The results indicate that both the abnormalities in MMP production and the overproduction of cytokines (in the presence of LPS or virus, which mimic inflammatory conditions) may be involved in bone destruction and tumor spread in multiple myeloma.
5

Molecular diagnostics of promyelocytic leukaemia

76%
Kocki J., Constantinou M., Cioch M., Lancut M., Kaluzewski B., Dmoszynska A., Wojcierowski J.
Journal of Applied Genetics
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2003
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vol. 44
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issue 4
553-556
EN
Acute promyelocytic leukaemia (APL) is characterised by proliferation of abnormal promyelocytes. The reciprocal translocation between the long arms of chromosomes 15 and 17, and the fusion between the retinoic acid receptor (RARa) gene, and PML gene, is unique to APL. Because of unsuccessful cytogenetic analysis of conventional G-banding technique (mitoses were not observed), we diagnosed three non-treatment patients with APL by following molecular methods: reverse transcription ? polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH). At the time of diagnosis our patients showed reciprocal translocation t(15;17)(q22;q12) in all cases studied (66-85% of positive bone marrow cells). With the use of CGH we observed the unbalanced chromosomal aberrations: losses of 5q13.1, 5q31.3, 9p21 regions, gain of 5q32 region and trisomy of 18 chromosome.
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