Прегледај по Аутор "Milev, Boško"

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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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    PD-1 BLOCKAGE FACILITATES CYTOTOXIC T AND NK CELLS TUMORICIDAL PHENOTYPE IN A MURINE BREAST CARCINOMA
    (Sciendo, 2023) Tripković, Sanja; Jocić, Miodrag; Stanisavljević, Isidora; Jovanović, Marina; Jurišević, Milena; Petrović, Andjela; Jovanović, Milan; Milev, Boško; Marić, Veljko; Jovanović, Marina
    In breast cancer therapy, as the leading cause of death in women, besides chemo-radiotherapy, immunotherapy has been increasingly used. PD-1/PD-L1 axis blockade primarily acts on T lymphocytes, the main effectors of acquired immune response. NK cells, which are part of the innate immune response, also play a role in the anti-tumor response through the blockade of this signaling pathway. The study was conducted to examine the effects of anti-PD-1 therapy on NK and T cells in mouse breast cancer. Female BALB/c mice were used, divided into two groups, one with induced breast cancer and one treated with anti-PD-1 antibody. Breast cancer cell line was used to induce the cancer, and the anti-PD-1 antibody was applied intraperitoneally. Cell populations in spleen and tumor microenvironment were examined using flow cytometry. Data were statistically analyzed using SPSS. The percentage of NK cells expressing FasL, NKG2D, and IFN-γ is significantly higher in spleen and tumor-infiltrating NK cells upon anti-PD-1 therapy, while the expression of inhibitory markers Foxp3 and IL-10 in regulatory NK cells is significantly lower. The percentage of T lymphocytes expressing CD107a and IL-17 is significantly higher in the spleen, while a higher number of T lymphocytes expressing CD69 is present in the tumor microenvironment. The study suggests that anti-PD-1 therapy can activate NK and T cells, and improve anti-tumor immune response in breast cancer. Further research is needed to understand the interplay between these cells during PD-1 blockage.
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    The Böhler’s angle in population of central Serbia – a radiological study
    (MDPI, 2018) Živanović-Mačužić, Ivana; Vulović, Maja; Vojinović, Radiša; Jovanović, Milan; Radunović, Aleksandar; Milev, Boško; Cvetković, Aleksandar; Stojiljković, Miloš; Milošević, Bojan; Ivošević, Anita; Aksić, Milan; Simović, Aleksandra; Jeremić, Dejan
    Background/Aim. The values of the Böhler’s angle (BA) are relevant parameters for diagnosis, management and prognosis of the calcaneal fracture and the outcome. Range of normal values of Böhler’s angle (BA) in adults varies depending on the examined population, age, gender or ethnicity. The aim of this study was to determine the range of normal values of the Böhler’s angle in the central part of Serbia. Methods. The lateral foot radiographs of 225 subjects (111 males and 114 females) without calcaneal fractures, divided into 6 age groups were observed to determine the normal values of the Böhler’s angle by using the IMPAX 6.5.2.114 Enterprise software. Obtained values for Böhler’s angle were compared among gender and groups using appropriate statistical tests. Results. The mean of Böhler’s angle in observed population was 34.06°, ranging from 25.1° to 49.5° and was higher in males than in females included in our study. Gender difference was statistically significant. The distribution of the mean BA across the age groups showed tendency of decreasing with age and the highest BA was found in the youngest group. Conclusion. The findings presented in this paper confirmed the existence of wide range of BA values as well as its gender and age differences.