Olivera Mitrović Ajtić

• PhD
• Research Associate at Institute for Medical Research, Serbia

Thrombosis is a critical complication in lymphomas, driven by chronic inflammation. To observe this systemic mechanism, we evaluated inflammatory cytokines, neutrophil and monocyte activation, and platelet function in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Hodgkin lymphoma (HL), with and without thrombosis using ELISA...

Oral cancer ranks in the top 10 most prevalent malignancies worldwide. It is an aggressive tumor with frequent relapses and metastases and relatively modest survival rates that do not improve in spite of constantly evolving treatment modalities. Cancer stem cells are a subpopulation of tumor cells considered to be responsible not only for tumor ini...

Hydroxyurea (hydroxycarbamide, HU) arrests cells in the S-phase by inhibiting ribonucleotide reductase and DNA synthesis, significantly contributing to the release of nitric oxide (NO). We investigated the involvement of inducible NO synthase (NOS2) in the cytostatic effect of HU using in vitro shRNA-induced knockdown of the NOS2 transcript (NOS2kd...

Cancer-promoting proinflammatory microenvironment influences colorectal cancer (CRC) development. We examined the biomarkers of inflammation, intestinal differentiation, and DNA activity correlated with the clinical parameters to observe progression and prognosis in the adenocarcinoma subtype of CRC. Their immunohistology, immunoblotting, and RT-PC...

INTRODUCTION: Hydroxyurea (HU) is a chemotherapeutic acting mainly through inhibiting ribonucleotide reductase and DNA synthesis, while nitric oxide (NO) inducer/donor properties contribute significantly to its cytostatic properties. HU has been shown to strongly affect angiogenesis, and reduced levels of angiogenic factors in plasma accompany HU's...

Chronic inflammation has been identified in leukemias as an essential regulator of angiogenesis. B-chronic lymphocytic leukemia (CLL) cells secrete high levels of vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1 alpha (HIF1α). The aim was to assess the role of inflammation in activation of angiogenic factors: endothelial nit...

CONCLUSION Thromboembolic events are a common complication of lymphoma, influenced by a number of factors, including status of the disease, patient characteristics and treatment modalities. Recent studies demonstrated presence of hemostatic dysregulation in lymphoma patients with the possible involvement of tissue factor (TF) in the development of...

The severity and mortality of coronavirus disease 2019 (COVID-19) are greater in males than in females, though the infection rate is the same in the two sexes. We investigated sex hormone differences associated with the hyperinflammatory immune response to SARS-CoV-2 on the basis of patients’ cytokine profiles and vaccination statuses. Clinical and...

Due to the development of resistance to previously effective therapies, there is a constant need for novel treatment modalities for metastatic melanoma. Nischarin (NISCH) is a druggable scaffolding protein reported as a tumor suppressor and a positive prognostic marker in breast and ovarian cancers through regulation of cancer cell survival, motili...

Transforming growth factor-beta1 (TGF-β) regulates a plethora of cell-intrinsic processes that modulate tumor progression in a context-dependent manner. Thus, although TGF-β acts as a tumor suppressor in the early stages of tumorigenesis, in late stages, this factor promotes tumor progression and metastasis. In addition, TGF-β also impinges on the...

Background Male sex is associated with greater severity and mortality from coronavirus disease 2019 (COVID-19), although infections are equally distributed between men and women. The present study aims to investigate sex differences in the hyperinflammatory immune response to SARS-CoV-2 infection and consequent thrombosis using linked cytokine prof...

The COVID-19 pandemic has had a strong impact on people's quality of life (QoL), which is affected by social and economic changes as well as by mental and physical health. The aim of this study was to determine QoL in post-COVID-19 patients who had required hospitalization, and to identify relevant sociodemographic data. We used questionnaires whic...

The calcium-binding proteins S100A4, S100A8, and S100A9 are upregulated in chronic lymphocytic leukemia (CLL), while the S100A9 promotes NF-κB activity during disease progression. The S100-protein family has been involved in several malignancies as mediators of inflammation and proliferation. The hypothesis of our study is that S100A proteins are m...

Purpose Melanoma is the deadliest form of skin cancer. Despite the advancements in targeted and immunotherapies, metastatic melanoma patients still have poor prognosis, and there is an urgent need for novel treatment modalities. Nischarin (NISCH) is a druggable scaffolding protein shown to be a tumor suppressor in breast cancer through regulation o...

Due to the development of resistance to previously effective therapies, there is a constant need for novel treatment modalities for metastatic melanoma. Nischarin (NISCH) is a druggable scaffolding protein reported as a tumor suppressor and a positive prognostic marker in breast and ovarian cancers through regulation of cancer cell survival, motili...

Although bone marrow-derived mesenchymal stromal cells (BM-MSCs) have been identified as a major cellular source of fibrosis, the exact molecular mechanism and signaling pathways involved have not been identified thus far. Here, we show that BM-MSCs contribute to fibrosis in myeloproliferative neoplasms (MPNs) by differentiating into αSMA-positive...

Chronic inflammation is characterized by the production of reactive oxygen species (ROS), reactive nitrogen species, and inflammatory cytokines in myeloproliferative neoplasms (MPNs). In addition to these parameters, the aim of this study was to analyze the influence of ROS on the proliferation-related AKT/mTOR signaling pathway and the relationshi...

In several systems, hydroxyurea has been shown to trigger nitric oxide (NO) release or activation of NO synthase (NOS). To elucidate this duality in its pharmacological effects, during myelosuppression, we individually examined hydroxyurea’s (NO releasing agent) and NO metabolites’ (stable NO degradation products) effects on erythroid colony growth...

Hydroxyurea (HU) is an antineoplastic agent that functions as an antimetabolite compound by inhibiting the ribonucleotide reductase. HU acts mainly as a cytostatic drug that through DNA replication stress may trigger a premature senescence-like cell phenotype, though its influence on bone marrow-derived mesenchymal stem/stromal cell (BMMSC) functio...

Hydroxyurea (HU) causes nitric oxide (NO) bioactivation, acting as both a NO donor and a stimulator of NO synthase (NOS). To examine whether HU effects are NO mediated by chemical degradation or enzymatic induction, we studied human and mouse erythroid cells during proliferation, apoptosis, and differentiation. The HU and NO donor demonstrated pers...

Background: Chronic inflammation has been recognized in neoplastic disorders, including myeloproliferative neoplasm (MPN), as an important regulator of angiogenesis. Aims: We investigated the influence of vascular endothelial growth factor (VEGF) and pro-inflammatory interleukin-6 (IL-6) on the expression of angiogenic factors, as well as inflammat...

The effects of a new material based on hydroxyapatite and calcium silicates, named ALBO-MPCA, were investigated on the liver, kidney and spleen. The material was administrated orally for 120 days in an in vivo model in Wistar rats, and untreated animals served as a control. Hematological and biochemical blood parameters were analyzed. Qualitative h...

Anaemia occurs frequently in patients with heart failure and its current treatment lacks clear targets. Emerging evidence suggests that erythroid progenitor cell expansion is an integral part of physiological response to anaemia associated with chronic stress. Understanding the underlying mechanism may provide a novel approach to anaemia management...

Novel three-dimensional (3D) nanohydroxyapatite-PLGA scaffolds with high porosity was developed to better mimic the mineral component and microstructure of natural bone. To perform a final assessment of this nanomaterial as a potential bone substitute, its toxicological profile was particularly investigated. Therefore, we performed a comet assay on...

This study has been performed to determine the mechanism of activation of the myeloid related S100A proteins by inflammatory cytokines in myeloproliferative neoplasm (MPN). Besides microarray analysis of MPN‐derived CD34⁺ cells, we analysed the pro‐inflammatory IL6 and anti‐inflammatory IL10 dependence of NF‐κB, PI3K‐AKT, and JAK‐STAT signalling du...

Aim To examine the potential systemic toxicity of nanostructured materials based on calcium silicate and calcium aluminate, for potential application in Dentistry. Methodology Twenty four Albino Wistar rats aged two months were used as an in vivo animal model for subcutaneous implantation of the investigated materials, placed in polyethylene tubes...

Hydroxyurea (HU) is a nonalkylating antineoplastic agent used in the treatment of hematological malignancies. HU is a DNA replication stress inducer, and as such, it may induce a premature senescence‐like cell phenotype; however, its repercussion on bystander cell proliferation has not been revealed so far. Our results indicate that HU strongly inh...

In accordance with increased proliferation in myeloproliferative neoplasm (MPN), the goal is to evaluate the immunoexpression of: β-catenin, PPAR-γ and Ki67 protein, to compare them with bone marrow ultrastructural characteristics in patients with MPN. Immunoexpression and electron microscopy of bone marrow was analyzed in 30 Ph-negative MPN patien...

Myeloproliferative neoplasms (MPNs) are developing resistance to therapy by JAK1/2 inhibitor ruxolitinib. To explore the mechanism of ruxolitinib's limited effect, we examined the JAK1/2 mediated induction of proliferation related ERK1/2 and AKT signaling by proinflammatory interleukin‐6 (IL‐6) in MPN granulocytes and JAK2V617F mutated human erythr...

Purpose: A common feature of malignancies is increased reactive oxygen species (ROS) and reactive nitrogen species (RNS). We analyzed the influence of oxidative and nitrosative stress on the activation of AKT/mTOR signaling pathway in myeloproliferative neoplasms (MPN). Methods: Oxidative stress-induced gene expression in circulatory CD34+ cells...

Purpose: Previously, the family of S100A proteins has been found to be associated with inflammation and myelopoiesis and to be able to induce or support myeloproliferation during chronic inflammation. Here, we studied the inflammatory myeloid-related proteins S100A4, S100A8, S100A9 and S100A12 in myeloproliferative neoplasms (MPNs) in order to ass...

Increased angiogenesis in BCR-ABL1 negative myeloproliferative neoplasms (MPNs) has been recognized, but its connection with clinical and molecular markers needs to be defined. The aims of study were to (1) assess bone marrow (BM) angiogenesis measured by microvessel density (MVD) using CD34 and CD105 antibodies; (2) analyze correlation of MVD with...

Endothelial cell markers are membrane-bound or cytoplasmic molecules expressed by endothelial cells, which help their easier identification and discrimination from other cell types. During vasculogenesis, endothelial cells differentiate from hemangioblasts to form new blood vessels. With the discovery of endothelial progenitor cells (EPC) and their...

Introduction: Philadelphia-negative myeloproliferative neoplasms (Ph(-) MPN) are characterized by overproduction of one or more blood cell lines. Methods: We studied the proliferative characteristics of 91 patients with de novo Ph(-) MPN. Colony-forming cells (CFC) and endogenous colonies (EC), from bone marrow (BM) and/or peripheral blood (PB),...

Diabetic gastroenteropathy involves not only the parasympathetic and sympathetic autonomic nerves, but also enteric neurons, smooth muscle cells and interstitial cells of Cajal (ICC). ICC are the cells of mesenchymal origin that occur within and around the muscle layers in the gastrointestinal tract. The objective of the present study was to invest...

Macrophage migration inhibitory factor is a well-known proinflammatory cytokine that is released during systemic stress response. Although MIF can affect erythrocyte production, the role of this cytokine in stress-induced erythropoiesis is completely unknown. To extend our previous findings showing that chronic psychological stress stimulates extra...

It has been shown that angiogenesis and inflammation play an important role in development of most hematological malignancies including the myeloproliferative neoplasm (MPN). The aim of this study was to investigate and correlate the levels of key angiogenic molecules such as hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor...

Background/aim: The purpose of this study was to investigate proliferation and differentiation markers in colorectal adenocarcinoma and their correlation with clinicopathological factors. Materials and methods: Samples were collected from 38 patients with colorectal adenocarcinoma and 10 healthy controls. E-cadherin, carcinoembryonic antigen (mC...

Purpose: We compared the gene expression profile of peripheral blood CD34(+) cells and granulocytes in subjects with chronic myeloid leukemia (CML), with the accent on signaling pathways affected by BCR-ABL oncogene. Methods: The microarray analyses have been performed in circulating CD34(+) cells and granulocytes from peripheral blood of 7 subj...

The recent JAK1/2 inhibitor trial in myeloproliferative neoplasms (MPNs) showed that reducing inflammation can be more beneficial than targeting gene mutants. We evaluated the proinflammatory IL-6 cytokine and JAK-STAT signaling pathway related genes in circulating CD34 + cells of MPNs. Regarding laboratory data, leukocytosis has been observed in p...

The statistical analyses of total gene expression in MPNs according to JAK2V617F mutant allele burden. We observed 261 significantly changed genes in PV, 82 significantly changed genes in ET, and 94 genes in PMF comparing to healthy subjects.

Stress evokes an integrated neuroendocrine response perturbing the homeostasis of different physiological systems. In contrast to well established physiologica linteractions between neuroendocrine and immune systems during chronic stress, there has been relatively little information on the effects of psychological stress on erythroid cells. Since s...

Standard risk stratification for overall survival (OS) in patients with essential thrombocythemia (ET) is based on advanced age and history of thrombotic events. Recently, International Prognostic Score for ET (IPSET) incorporated also leukocytosis in prognostic model. The aim of this study was to establish additional risk factors for OS in ET pati...

Abstract. Interstitial cells of Cajal (ICC) play important roles in the control of digestive motility: they generate the electrical slow-wave activity (pacemaker component) of the gut musculature and are involved in neurotransmission and stretch sensation. ICC expresses c-kit and depends on signaling via Kit receptors for development and maintenan...

Psychological stress affects different physiological processes including haematopoiesis. However, erythropoietic effects of chronic psychologi-cal stress remain largely unknown. The adult spleen contains a distinct microenvironment favourable for rapid expansion of erythroid progeni-tors in response to stressful stimuli, and emerging evidence sugge...

The aim of our study was to investigate HER-2 and TOP2A gene status and their correlation with Bcl-2, p53, Ki67, ssDNA, and clinicopathological parameters in four molecular subtypes of breast cancer. Seventy-four paraffin-embedded samples are immunohistochemically studied for the expression of estrogen receptor (ER), progesterone receptor (PR), HER...

The emergence of multiple myeloma as a second malignancy in patients with essential thrombocythemia is extremely rare. Several cases have been published so far, pointing out the impact of a cytotoxic effect during treatment of essential thrombocythemia on the development of multiple myeloma. We report the case of a 52-year-old Caucasian man who pre...

Abstract - We studied TOP2A amplification (using FISH methods), and TOP2A and BRCA1 protein overexpression (immunohistochemistry) in four molecular subtypes of breast cancer. Of 53 patients, 32 showed TOP2A and 38 showed BRCA1 overexpression. The highest percentage of TOP2A amplification (47.8%) and deletion (13%) was detected in Luminal B subtypes...

Objective. Although it is known that nitric oxide modulates the activity of hypothalamic-pituitary-adrenal axis, its functional significance has not been elucidated. Additionally, there is no information on the effect of nitric oxide on cortical expression of glucocorticoid receptor. The purpose of this study was to investigate the influence of end...

Objective. Although it is known that nitric oxide modulates the activity of hypothalamic-pituitary-adrenal axis, its functional significance has not been elucidated. Additionally, there is no information on the effect of nitric oxide on cortical expression of glucocorticoid receptor. The purpose of this study was to investigate the influence of end...

Aims: We showed previously that the acute effect of ethanol on intestinal immunoglobulin A (IgA) expression might be mediated by endogenous nitric oxide (NO). To extend these findings, this study was designed to investigate a possible role of neuronal NO synthase (nNOS) in the observed phenomenon, using 7-nitroindazole (7-NI), a selective inhibito...

Background: This study was performed to investigate expression and distribution of glucocorticoid receptor (GR) in the rat adrenal cortex, acute effect of ethanol on its expression and possible role of endogenous nitric oxide (NO) in this phenomenon. Methods: Adult female Wistar rats showing diestrus day 1 were treated with: a) ethanol (2 or 4 g...

Background: Since reports on endocrine cells and their kinetics in the corpus of the human stomach are limited, the aim of this study was to examine the appearance, localization, density, and the relationship among the endocrine cell types in the corpus of the human stomach during prenatal and early postnatal development. Methods: We examined ch...

The pancreas appears to be a major source of ghrelin during fetal development, but the ontogeny of ghrelin cells in the human pancreas and their developmental relationship with α- and β-cells remain largely unknown. In the present study, we examined the dynamics of ghrelin cell growth, colocalization of ghrelin with major pancreatic hormones and de...

The present study was designed to investigate a possible role of endogenous nitric oxide (NO) in the adrenal response to an acute alcohol administration in female rats. To this end, N(ω)-nitro-L-arginine-methyl ester (L-NAME), a competitive inhibitor of all isoforms of NO synthase, was used. Adult female Wistar rats showing diestrus Day 1 were trea...

The aim of this study was to investigate the appearance, localization and density of ghrelin cells in the human stomach during prenatal development. For this purpose the antrum and corpus of embryos, fetuses and infants are stained immunohistochemically by the streptavidin-biotin technique. The presence of P/D1 cells at 11 weeks of fetal developmen...

Interstitial cells of Cajal (ICC) are morphologically and functionally intercalated between the elements of the enteric nervous system and the smooth muscle cells (SMCs) in the musculature of the digestive tract. Kit immunohistochemistry reliably identifies the location of these cells and provides information on changes in ICC distribution and dens...

Megacolon refers to an abnormal dilatation of the colon. This condition occurs in both humans and animals. Although it seems to be more common in cats, megacolon may also occur in dogs. However, data regarding the etiopathogenesis, clinical course and outcome of canine megacolon are scarce. The aim of this study is to present the experience of our...

Large-cell neuroendocrine carcinoma is a high-grade neuroendocrine carcinoma, originally described in the lung. The tumor rarely occurs in extrapulmonary sites like the gastrointestinal tract, and only few examples have been described in the ampulla of Vater. A new case of large-cell neuroendocrine carcinoma of the ampulla of Vater in a 60-year-old...

Nitric oxide (NO) is known as a regulator of inflammation and immunity. The purpose of this study was to investigate the influence of this signal molecule on the rat immunoglobulin A (IgA) system using Nomega-nitro-L-arginine-methyl ester (L-NAME), which inhibits the activity of all isoforms of NO synthase. The experiments were performed on adult f...

Some studies indicate that diabetes mellitus exerts an influence on the gastrointestinal tract and its diffuse neuroendocrine system (DNES) in regard to cellular density and neuroendocrine content. Since there is no data about relationship between experimentally induced non-insulin-dependent (type 2) diabetes mellitus (NIDDM) on the gut K cells, th...