Прегледај по Аутор "Jocić, Miodrag"

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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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    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.