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1.  Expression of Toll-Like Receptors 3, 7, and 9 in Peripheral Blood Mononuclear Cells from Patients with Systemic Lupus Erythematosus 
Mediators of Inflammation  2014;2014:381418.
Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown aetiology. The results of experimental studies point to the involvement of innate immunity receptors—toll-like receptors (TLR)—in the pathogenesis of the disease. The aim of the study was to assess the expression of TLR3, 7, and 9 in the population of peripheral blood mononuclear cells (PBMC) and in B lymphocytes (CD19+), T lymphocytes (CD4+ and CD8+) using flow cytometry. The study group included 35 patients with SLE and 15 healthy controls. The patient group presented a significantly higher percentage of TLR3- and TLR9-positive cells among all PBMCs and their subpopulations (CD3+, CD4+, CD8+, and CD19+ lymphocytes) as well as TLR7 in CD19+ B-lymphocytes, compared to the control group. There was no correlation between the expression of all studied TLRs and the disease activity according to the SLAM scale, and the degree of organ damage according to the SLICC/ACR Damage Index. However, a correlation was observed between the percentage of various TLR-positive cells and some clinical (joint lesions) and laboratory (lymphopenia, hypogammaglobulinemia, anaemia, and higher ESR) features and menopause in women. The results of the study suggest that TLR3, 7, and 9 play a role in the pathogenesis of SLE and have an impact on organ involvement in SLE.
doi:10.1155/2014/381418
PMCID: PMC3955595
2.  New Insights into Biology, Prognostic Factors, and Current Therapeutic Strategies in Chronic Lymphocytic Leukemia 
ISRN Oncology  2013;2013:740615.
Chronic lymphocytic leukemia (CLL) is characterized by the clonal proliferation and accumulation of mature B lymphocytes. CLL cells show an antiapoptotic profile, suggesting the important role of apoptosis inhibition in the disease development. However, there is some population of proliferating CLL cells, which may also play a role in progression of the disease. There are several newer, biological prognostic factors in CLL. Currently, cytogenetic abnormalities with different prognostic values seem to be the most biologically relevant. During the last decades, the treatment of CLL has been significantly changed. Different strategies such as monotherapy with chlorambucil and purine nucleoside analogues (PNA) used alone or in combination with cyclophosphamide have been introduced. Most recently, immunochemotherapy with anti-CD20 monoclonal antibody, rituximab, combined with fludarabine and cyclophosphamide, became a gold standard of first-line treatment in eligible CLL patients. Currently, new treatment strategies including new monoclonal antibodies, bendamustine, lenalidomide, or inhibitors of several cell signaling pathways are under clinical studies in resistant/relapsed CLL patients. Moreover, allogeneic stem cell transplantation has to be considered, especially in younger high risk patients, for example, those who are resistant to PNA or those with 17p deletion. In this paper, we present the most important recent advances in CLL biology and treatment.
doi:10.1155/2013/740615
PMCID: PMC3763269  PMID: 24027642
3.  Helicobacter pylori Infection, Chronic Inflammation, and Genomic Transformations in Gastric MALT Lymphoma 
Mediators of Inflammation  2013;2013:523170.
Nowadays, it is believed that the main role in the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma plays Helicobacter pylori infection. This world-wide distributed bacteria is in charge of most cases of not only upper gastrointestinal tract disorders but also some of extragastric problems. Constant stimulation of the immune system causes a B-lymphocytes proliferation, which is considered to be responsible for the neoplastic transformation. On the other hand, there are 10%–20% of patients who do not respond to Helicobacter pylori eradication treatment. This group has often a chromosome translocation, which suggests that there is another unknown, so far, pathogenetic mechanism of MALT lymphoma. Majority of genetic abnormalities are connected with nuclear factor-κB (NF-κB) pathway, which activates the uncontrolled proliferation of neoplastic cells. Translocations already described in studies are t(11;18)(q21;q21), which is the most common, t(14;18)(q32;q21), t(14;18)(q32;q21), and t(3;14)(p14.1;q32). This non-Hodgkin's lymphoma is an indolent type originated outside lymph nodes. In more than 50% of cases, it occurs in the stomach. Occasionally, it can be found in salivary and thyroid gland, lung, breast, bladder, skin, or any other place in the human body. This paper is a review of the current knowledge on etiology, pathogenesis, treatment, and follow-up of gastric MALT lymphoma.
doi:10.1155/2013/523170
PMCID: PMC3625579  PMID: 23606792
4.  Impaired apoptosis of megakaryocytes and bone marrow mononuclear cells in essential thrombocythemia: correlation with JAK2V617F mutational status and cytoreductive therapy 
Essential thrombocythemia (ET) is a clonal myeloproliferative disorder characterized by overproduction of megakaryocytes (MKCs) and platelets. The recent discovery of the JAK2 mutation has shed a new light on the development of ET but its pathogenesis still remains unknown. One of the possible mechanisms can be deregulation of apoptosis, resulting in accumulation of bone marrow MKCs. In this study, we investigated the apoptotic profile, as well as the expression of apoptosis-regulating protein in MKCs and bone marrow mononuclear cells (BMMCs) in 43 patients with ET. We found significantly lower percentages of apoptotic MKCs and BMMCs, as measured by the rate of annexin-V+ and caspase-3+ (Cas-3+) cells in relation to healthy volunteers. Additionally, the expression of Bax protein in ET patients naïve to cytoreductive treatment, as well as their Bax/Bcl-2 ratio, was significantly lower than in controls (p = <0.05 and p < 0.001, respectively). Patients positive for the JAK2V617F mutation had markedly higher activation of Cas-3, as well as higher Bax expression (p = 0.02 and p = 0.04, respectively) than JAK2V617F negative cases. There were no marked differences between patients already treated with anagrelide (ANA) or hydroxyurea (HU), although tendency toward the higher apoptosis rate was observed in the HU-treated group. In conclusion, these results demonstrate the inhibition of caspase-dependent apoptosis of both MKCs and BMMCs in untreated ET. This is associated with upregulation of Bcl-2 and downregulation of Bax proteins, predominantly in JAK2V617F negative cases. Patients treated with HU showed slightly higher pro-apoptotic Bax/Bcl-2 index than patients on ANA therapy, which may influence the better efficacy of HU therapy in ET.
doi:10.1007/s12032-012-0202-3
PMCID: PMC3466431  PMID: 22418850
Essential thrombocythemia; Apoptosis; Anagrelide; Hydroxyurea; JAK2V617F mutation
5.  Laser scanning cytometry for automation of the micronucleus assay 
Mutagenesis  2011;26(1):153-161.
Laser scanning cytometry (LSC) provides a novel approach for automated scoring of micronuclei (MN) in different types of mammalian cells, serving as a biomarker of genotoxicity and mutagenicity. In this review, we discuss the advances to date in measuring MN in cell lines, buccal cells and erythrocytes, describe the advantages and outline potential challenges of this distinctive approach of analysis of nuclear anomalies. The use of multiple laser wavelengths in LSC and the high dynamic range of fluorescence and absorption detection allow simultaneous measurement of multiple cellular and nuclear features such as cytoplasmic area, nuclear area, DNA content and density of nuclei and MN, protein content and density of cytoplasm as well as other features using molecular probes. This high-content analysis approach allows the cells of interest to be identified (e.g. binucleated cells in cytokinesis-blocked cultures) and MN scored specifically in them. MN assays in cell lines (e.g. the CHO cell MN assay) using LSC are increasingly used in routine toxicology screening. More high-content MN assays and the expansion of MN analysis by LSC to other models (i.e. exfoliated cells, dermal cell models, etc.) hold great promise for robust and exciting developments in MN assay automation as a high-content high-throughput analysis procedure.
doi:10.1093/mutage/geq069
PMCID: PMC3107611  PMID: 21164197

Results 1-5 (5)