Прегледај по Аутор "Jurišević, Milena"

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    Anti-PD-1 therapy activates tumoricidic properties of NKT cells and contributes to the overall deceleration of tumor progression in a model of murine mammary carcinoma
    (University of Defense, Ministry of Defence of the Republic of Serbia, Belgrade, Serbia, 2022) Jovanović, Marina; Gajović, Nevena; Jurišević, Milena; Sekulić, Sofija; Arsenijević, Nebojša; Jocić, Midrag; Jovanović, Milan; Lukić, Ružica; Jovanović, Ivan; Radovanović, Dragče
    Background/Aim. Immune checkpoint therapy is a well-established therapeutic approach in the treatment of malig-nant diseases and is thought to be mostly based on facilitat-ing the adaptive immune response. However, the cells of the innate immune response, such as natural killer T (NKT) cells, might also be important for a successful anti-programmed cell death protein-1 (anti-PD-1) therapy, as they initiate the antitumor immune response. The aim of this study was to investigate the influence of anti-PD-1 therapy on the immune response against tumors. Methods. For tumor induction, 4T1 cells synergic to BALB/c back-ground were used, after which mice underwent anti-PD-1 treatment. After the mice were sacrificed, NKT cells, den-dritic cells (DCs), and macrophages derived from spleen and primary tumor tissue were analyzed using flow cytome-try. Results. Anti-PD-1 therapy enhanced the expression of activating molecules CD69, NKp46, and NKG2D in NKT cells of the tumor and spleen. This therapy activated NKT cells directly and indirectly via DCs. Activated NKT cells acquired tumoricidic properties directly, by secreting perfor-in, and indirectly by stimulating M1 macrophages polariza-tion. Conclusion. Anti-PD-1 therapy activates changes in DCs and macrophages of primary tumor tissue towards protumoricidic activity. Since anti-PD-1 therapy induces significant changes in NKT cells, DCs, and macrophages, the efficacy of the overall antitumor response is increased and has significantly decelerated tumor growth.
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    Colorectal carcinoma: evaluation of systemic values of interleukin-1 and interleukin-33 in patients with and without thrombocytosis
    (Ministry of Defance, Serbia, 2021) Jocić, Miodrag; Gajović, Nevena; Jurišević, Milena; Jovanović, Marina; Zdravković, Nataša; Arsenijević, Nebojša; Vuković Dejanović, Vesna; Marić, Veljko; Milev, Boško; Jovanović, Milan
    Background/Aim. Reactive thrombocytosis, as a parane-oplastic syndrome, is often observed in cancer patients. A variety of tumor-related humoral factors and cytokines con-tribute to tumor-stimulated thrombopoiesis. However, the exact role of these cytokines in the pathogenesis of throm-bocytosis remains unclear. The aim of this study was to ana-lyze systemic values of cytokines and clinical-pathological characteristics in colorectal carcinoma (CRC) patients with and without thrombocytosis. Methods. Fifty nine CRC pa-tients were involved in this study and divided into two groups according to the number of platelets. We recorded and analyzed the data about: age, gender, size of the cancer, localization, metastasis, vascular or lymph vessel invasion, nuclear grade, histological differentiation rate, tumor, no-dus, metastasis (TNM) stage and concentration of cytokines [interleukin (IL)-1, IL-33, IL-12, IL-17 and interferon (IFN)-γ] in both groups. Results. CRC patients with thrombocytosis had significantly higher nuclear grade of the cancer (p = 0.002); higher percentage of detectable metastat-ic lesions in the liver (p = 0.002), lung (p = 0.001), peritoneal carcinomatosis (p = 0.001), detectable invasion of blood (p= 0.012) and lymph vessels (p = 0.010). Concentrations of tumor markers [alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9)] and se-rum values of IL-1 and IL-33 were significantly higher in CRC patients with thrombocytosis. IL-1/IL-12 (p = 0.016), IL-1/IFN-γ (p = 0.007), IL-1/IL-17 (p = 0.006), IL-33/IL-12 (p = 0.001), IL-33/IFN-γ (p = 0.001), IL-33/IL-17 (p = 0.002), and IL-33/IL-1 (p = 0.006) ratios were significantly higher in CRC patients with thrombocytosis in comparison to CRC patients without thrombocytosis. Analysis of Re-ceiver Operating Characteristic (ROC) curves showed that values of IL-1 [area under curve (AUC) = 0.718; 95% con-fidence interval (CI): 0.567–0.868; sensitivity 69.2%, speci-ficity 62.9%] and IL-33 (AUC = 0.763; 95% CI: 0.614–0.911; sensitivity 84.6%, specificity 65.7%)], could be serve as possible markers for paraneoplastic thrombocytosis in CRC patients. Conclusion. IL-1 and IL-33 significantly correlated to high thrombocyte number in patients with more aggressive CRC.
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    Fecal galectin-1 as a potential marker for colorectal cancer and disease severity
    (Ministry of Defance, Serbia, 2019) Jovanović, Milan; Gajović, Nevena; Zdravković, Nataša; Jovanović, Marina; Jurišević, Milena; Vojvodić, Danilo; Mirković, Darko; Milev, Boško; Marić, Veljko; Arsenijević, Nebojša
    Background/Aim. Colorectal cancer (CRC) represents one of the most common cancers worldwide. CRC is frequently diagnosed at advanced stages with poor prognosis, indicating the need for new diagnostic and prognostic markers. The aim of this study was to determine systemic and fecal values of galectin- 1 (gal-1) and ratios between gal-1 and proinflammatory cytokines: tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interferon gamma (IFN-γ), in the patients with CRC and the relationship with clinicopathological aspects of the disease. Methods. The blood samples and feces liquid fraction of 58 patients with CRC were analyzed. The serum and fecal levels of TNF-α, IL-1β and IFN-γ and gal-1 were measured using sensitive enzyme-linked immunosorbent assay (ELISA) kits. Results. The fecal level of gal-1 was increased in the CRC patients with higher nuclear grade and poor tumor tissue differentiation. The gal-1/TNF-α ratio in the serum and feces had a higher trend in the patients with the advanced tumor-nodemetastasis (TNM) stage as well as the detectable lymphatic and blood vessel invasion. The gal-1/TNF-α and gal-1/IFN-γ ratios were increased in the serum of patients with presence of lung/liver metastasis or peritoneal carcinomatosis, while the enhanced gal-1/IL-1 ratio was detected only in the serum of patients with lung metastasis. A positive correlation between the gal-1 value in feces and histological differentiation of tumor and biomarkers alpha-fetoprotein (AFP) and cancer antigen- 19-9 (CA 19-9), respectively, was also observed. The fecal values of gal-1 higher than 13,708.29 pg/g presented a highly sensitive and specific marker for histological differentiation of tumor tissue. Conclusion. We believe that the predomination of gal-1 over pro-inflammatory cytokines TNF-α, IL-1β and IFN- γ in the patients with advanced and progressive CRC may implicate on an immunomodulatory role of gal-1 in the limiting ongoing proinflammatory processes. The fecal values of gal-1 can be used as a valuable marker for the severity of CRC.
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    Fecal sST2 correlates with the disease severity of ulcerative colitis
    (Ministry of Defance, Serbia, 2019) Jovanović, Marina; Gajović, Nevena; Jurišević, Milena; Simović Marković, Bojana; Marić, Veljko; Jovanović, Milan; Arsenijević, Nebojša; Zdravković, Nataša
    Background/Aim. Ulcerative colitis (UC) is a chronic, relapsing inflammatory disease affecting the distal colon and rectum with complex pathogenesis and diagnosis, indicating the need for new diagnostic and prognostic markers. The aim of this study was to determine the fecal values of TNF- α, IL-17, IL-10 and soluble protein ST2 (sST2) in the patients with UC and their relationship with clinicopathological aspects. Methods. The samples of stool of 80 patients with UC were analyzed. Concentrations of TNF-α, IL-17, IL-10 and sST2 were measured by ELISA. Results. Concentrations of TNF-α, IL-17 and sST2 were significantly increased in the feces of patients with the higher endoscopic, clinical and total Mayo score, as well as in the patients with an intense crypt destruction, erosion of the mucous membranes, architectural changes, neutrophil infiltration and eosinophil infiltration. The local value of anti-inflammatory cytokine IL-10 in liquid fraction of feces was increased in the patients with an advanced endoscopic stage of UC. The moderate positive correlation between the fecal sST2/IL-17 and the clinical and histological parameters of disease severity and also the strong correlation between sST2 and IL-17 was also observed in the feces of patients with UC. The analysis of receiver operating characteristic (ROC) curves showed that the optimal cut-off value for sST2 of 624.0 pg/g allows the discrimination of clinical stages of UC. Conclusion. The increased fecal value of sST2 in the UC patients with a higher endoscopic, clinical and histological stage of disease may be considered as a sign of the disease severity. The fecal values of sST2 can be used as a valuable marker for UC severity