The importance of the differences in immunoglobulin levels specific for melanin and tyrosinase in antitumor immunity in patients with melanoma

Melanom je visoko imunogeno maligno oboljenje. Melanomski antigeni imaju sposobnost imunizacije i stimulacije sinteze specifičnih antitela. Antitela specifična za iste, melanomske antigene, koji su prisutni kako na neoplastično transformisanim, tako i na neizmenjenim melanocitima, pronađeni su i kod bolesnika sa vitiligom. Pojava hipopigmentacija sličnih vitiligu kod bolesnika sa melanomom utiče na bolju prognozu preživljavanja, što ukazuje na značaj veze između tumorske imunosti i autoimunosti kod ovih bolesnika. Ćelije melanoma karakteriše povećano prisustvo melanina i tirozinaze, a u serumu bolesnika sa metastatskim melanomom uočena je tirozinazna aktivnost. Dipeptidil peptidaza IV (DPPIV/CD26) je transmembranski glikoprotein koji se eksprimira na površini limfocita, i predstavlja važan marker aktivacije ćelija imunskog sistema. Upravo su limfociti jedan od najznačajnijih izvora solubilne forme ovog proteina u serumu. DPPIV ima značajnu ulogu u regulaciji imunskih funkcija i procesu neoplastične transformacije. Osnovni cilj ovog istraživanja je bio da se ispitaju razlike u nivoima IgG, IgA i IgM klasa antitela specifičnih za melanin i tirozinazu u bolesnika sa melanomom u odnosu na bolesnike sa vitiligom i zdrave osobe. Od značaja je bilo i da se ispita postojanje razlika u humoralnom imunskom odgovoru između bolesnika sa melanomom bez metastaza i bolesnika sa melanomom i metastazama. S ciljem dodatne karakterizacije imunskog odgovora, određivan je procenat CD16+ i CD16+CD56+ limfocita, i CD89+ granulocita kod bolesnika sa melanomom, kao i bolesnika sa vitiligom i zdravih osoba, a zatim je ispitivana povezanost nivoa antitela i CD16/CD89+ ćelija u grupi bolesnika sa melanomom...Melanoma is a highly immunogenic malignancy. Melanoma antigens are capable of immunization and stimulation of the synthesis of specific antibodies. Antibodies specific for same, melanoma antigens, which are present both on the neoplastically transformed, as well as on the non-transformed melanocytes, were also found in patients with vitiligo. The presence of vitiligo-like hypopigmentations in patients with melanoma is associated with a better survival prognosis, indicating the importance of the link between tumor immunity and autoimmunity. The increased presence of melanin and tyrosinase is characteristic of melanoma cells, while the tyrosinase activity was observed in the sera of patients with metastatic melanoma. Dipeptidyl peptidase IV (DPPIV/CD26) is a transmembrane glycoprotein which is expressed on the surface of lymphocytes, and represents an important marker of activation of immune system cells. Lymphocytes represent one of the major sources of soluble form of this protein in the serum. DPPIV is implicated in the regulation of immune functions and neoplastic transformation. The main goal of this study was to examine the differences in the levels of IgG, IgA and IgM classes of antibodies specific for melanin and tyrosinase in patients with melanoma, compared with the group of patients with vitiligo and the group of healthy individuals. The examination of the presence of differences in the humoral immune response between patients with melanoma without metastases and patients with melanoma and metastases was also significant for our research. To further characterize the immune response, it was important to determine the percentage of CD16+ and CD16+CD56+ lymphocytes and CD89+ granulocytes in patients with melanoma, as well as patients with vitiligo and healthy persons, and also to investigate the connection between the levels of antibodies and CD16/CD89+ cells in the group of patients with melanoma..

Hypericum perforatum L. extracts exert cytotoxic effects and show different miRNA signatures in PC-3 and DU 145 prostate cancer cells

Phytochemicals and bioactive substances derived from a wide range of plant extracts have been reported to exert various anticancer effects. Prostate cancer is one of the leading causes of cancer-related deaths within the male population. Prostate cancer-specific miRNA signatures were associated with cancer formation and progression, with various subtypes, and response to therapy. MicroRNA levels of expression were shown to change after the treatment of various compounds and substances extracted from natural products. Natural herbal compounds were shown to induce variations in miRNA expression levels in cancer cells. The aims of this study were to investigate the cytotoxic effects of methanol, ethyl-acetate, and hexane extracts obtained from branch-body part and flowers of Hypericum perforatum L. against humane PC-3 and DU 145 and to test potential miRNA-128/133b/155/193a/206/21/335 signature changes and differences between the two prostate cancer cell lines. Cytotoxic activity of H. perforatum extracts, their effects on cell cycle distribution, and miRNA expression levels were examined in humane PC-3 and DU 145 prostate cancer cells by MTT cell survival assay, flow cytometry, and quantitative real-time PCR. Hexane extract of flowers showed the strongest intensity of cytotoxic activity against PC-3 and DU 145 cells. The highest increase in the percentage of PC-3 cells in the subG1 phase was observed in cell samples treated with hexane extract of flowers and branch-body part. Significant differences in miRNA-128/133b/155/193a/206/21/335 levels were observed between PC-3 and DU 145 cell lines, especially in samples treated with flower extracts compared with the branch-body part. Conclusions: Investigated extracts have significant anticancer potential not only from the aspects of cytotoxicity and cell cycle effects but also from the aspect of lowering oncogenic or increasing tumor-suppressive miRNAs. The best effect might be the increase of tumor-suppressive miR-128 (accompanied by miR-193a) induced by the hexane extract of the flowers, which also exerted the highest cytotoxic activity. Hexane extract of flowers may be the candidate for further investigation for improving the efficiency of standard therapies for PCa. A miRNA signature might be cell-type specific after the treatment with H. perforatum extracts

Phenolic constituents, antioxidant, α-amylase and α-glucosidase inhibitory activities of Pyrus × velenovskyi bark

Pyrus × velenovskyi Dostálek (Rosaceae) [P. pyraster (L.) Burgsd. × P. spinosa Forssk.] is a deciduous tree up to 5 m height. Leaf-blades 2.2–4.8 × 1.3–2.7 cm, ± glabrate, ellip tic, gradually narrowed to a rather long petiole. Th is natural hybrid plant was described from Bulgaria, and has been also found in Serbia. The objective of this work was to investigate the phenolic profile, as well as in vitro antioxidant, α-amylase and α-glucosidase inhibitory activities of dried methanol ex tract from the bark of this tree. The plant material was collected in eastern Serbia (Jelašnička Klisura gorge). In the dried bark, the contents of different classes of phenolics were spectrophotometrically determined: total polyphenols (10.36%), tannins (8.78%), procyanidins (4.21%) and phenolic glycosides (3.54%). After pre-extraction with dichloromethane, powdered bark was extracted with methanol by bimaceration at room temperature. In obtained dried methanol extract, using aforementioned spectrophotometric tests, the contents of total polyphenols (33.42%) and tannins (21.55%) were determined, and by HPLC, arbutin, chlorogenic acid, catechin and procyanidin B2 were identifi ed. Its antioxidant activity, i.e. ferric reducing capacity (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and OH radical scavenging ability, as well as the inhibition of the enzymes α-amylase and α-glucosidase were assessed using corresponding colorimetric assays. Tested dried methanol extract exhibited signifi cant DPPH and OH radical scavenging abilities (SC50 = 6.85 and 12.21 μg/mL, respectively), and ferric reducing capacity (10.74 mmol Fe (II)/g of dried extract), as well as the inhibition of α-amylase (IC50 = 11.4 μg/mL) and α-glucosidase (IC50 = 5.48 μg/mL).7th Balkan Botanical Congress, 10-14th September 2018, Novi Sad, Serbia

Supplementary data for article: Pantelić, N.; Zmejkovski, B. B.; Kolundžija, B.; Crnogorac, M. Đ.; Vujić, J. M.; Dojčinović, B.; Trifunović, S. R.; Stanojković, T. P.; Sabo, T. J.; Kaluđerović, G. N. In Vitro Antitumor Activity, Metal Uptake and Reactivity with Ascorbic Acid and BSA of Some Gold(III) Complexes with N,N′-Ethylenediamine Bidentate Ester Ligands. Journal of Inorganic Biochemistry 2017, 172, 55–66. https://doi.org/10.1016/j.jinorgbio.2017.04.001

Supplementary material for: [https://doi.org/10.1016/j.jinorgbio.2017.04.001]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2478]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3070

Supporting information for: "Cu(II), Mn(II) and Zn(II) complexes of hydrazones with a quaternary ammonium moiety: synthesis, experimental and theoretical characterization and cytotoxic activity"

In this paper, Cu(II), Mn(II) and Zn(II) complexes with N,N,N-trimethyl-2-oxo-2-(2-(1-(thiazol-2-yl)ethylidene)hydrazinyl)ethan-1-aminium chloride (HL1Cl) were synthesized and characterized by single-crystal X-ray diffraction, IR spectroscopy, elemental analysis and DFT calculations. In all three complexes, a ligand (L1) is coordinated in a deprotonated formally neutral zwitterionic form via NNO donor set atoms. Cu(II) and Zn(II) form mononuclear penta-coordinated complexes [CuL1(N3)(CH3OH)]BF4 and [ZnL1(N3)2], respectively, while Mn(II) forms a binuclear [Mn2L12(μ-1,1-N3)2(N3)2]·2CH3OH complex, with unusual distorted trigonal-prismatic geometry around the metal centers. The antimicrobial activity of these complexes was tested against a panel of Gram-negative and Gram-positive bacteria, two yeasts and one fungal strain. The binuclear Mn(II) complex showed antifungal activity of similar intensity to amphotericin B. Based on the results of the brine shrimp test and DPPH radical scavenging activity, the most active Cu(II) and Mn(II) complexes were selected for evaluation of cytotoxic activity against five malignant cancer cell lines (HeLa, A375, MCF7, PC-3 and A549) and one normal cell line HaCaT. Both complexes showed significant activity. It should be pointed out that the activity of the Mn(II) complex against the MCF7 breast cancer cell line is only slightly weaker than that of cisplatin, but with selectivity to the tumor cell line in comparison to normal HaCaT cells, which is non-existent in the case of cisplatin.The supporting information for: Stevanović, Nevena, Zlatar, Matija, Novaković, Irena, Pevec, Andrej, Radanović, Dušanka, Matić, Ivana Z., Đorđić Crnogorac, Marija, Stanojković, Tatjana, Vujčić, Miroslava, Gruden, Maja, Sladić, Dušan, Anđelković, Katarina, Turel, Iztok, Čobeljić, Božidar, "Cu(II), Mn(II) and Zn(II) complexes of hydrazones with a quaternary ammonium moiety: synthesis, experimental and theoretical characterization and cytotoxic activity" in Dalton Transactions, 51, no. 1 (2022):185-196, [https://doi.org/10.1039/D1DT03169D]Published article: [https://cer.ihtm.bg.ac.rs/handle/123456789/4901]Related crystallographic data (CCDC 2110386): [https://cer.ihtm.bg.ac.rs/handle/123456789/4903]Related crystallographic data (CCDC 2110387): [https://cer.ihtm.bg.ac.rs/handle/123456789/4904]Related crystallographic data (CCDC 2110388): [https://cer.ihtm.bg.ac.rs/handle/123456789/4905

Cu(II), Mn(II) and Zn(II) complexes of hydrazones with a quaternary ammonium moiety: synthesis, experimental and theoretical characterization and cytotoxic activity

In this paper, Cu(II), Mn(II) and Zn(II) complexes with N,N,N-trimethyl-2-oxo-2-(2-(1-(thiazol-2-yl)ethylidene)hydrazinyl)ethan-1-aminium chloride (HL1Cl) were synthesized and characterized by single-crystal X-ray diffraction, IR spectroscopy, elemental analysis and DFT calculations. In all three complexes, a ligand (L1) is coordinated in a deprotonated formally neutral zwitterionic form via NNO donor set atoms. Cu(II) and Zn(II) form mononuclear penta-coordinated complexes [CuL1(N3)(CH3OH)]BF4 and [ZnL1(N3)2], respectively, while Mn(II) forms a binuclear [Mn2L12(μ-1,1-N3)2(N3)2]·2CH3OH complex, with unusual distorted trigonal-prismatic geometry around the metal centers. The antimicrobial activity of these complexes was tested against a panel of Gram-negative and Gram-positive bacteria, two yeasts and one fungal strain. The binuclear Mn(II) complex showed antifungal activity of similar intensity to amphotericin B. Based on the results of the brine shrimp test and DPPH radical scavenging activity, the most active Cu(II) and Mn(II) complexes were selected for evaluation of cytotoxic activity against five malignant cancer cell lines (HeLa, A375, MCF7, PC-3 and A549) and one normal cell line HaCaT. Both complexes showed significant activity. It should be pointed out that the activity of the Mn(II) complex against the MCF7 breast cancer cell line is only slightly weaker than that of cisplatin, but with selectivity to the tumor cell line in comparison to normal HaCaT cells, which is non-existent in the case of cisplatin.Related crystallographic data (CCDC 2110386): []Related crystallographic data (CCDC 2110387): []Related crystallographic data (CCDC 2110388): [

Supporting information for: "Cu(II), Mn(II) and Zn(II) complexes of hydrazones with a quaternary ammonium moiety: synthesis, experimental and theoretical characterization and cytotoxic activity"

In this paper, Cu(II), Mn(II) and Zn(II) complexes with N,N,N-trimethyl-2-oxo-2-(2-(1-(thiazol-2-yl)ethylidene)hydrazinyl)ethan-1-aminium chloride (HL1Cl) were synthesized and characterized by single-crystal X-ray diffraction, IR spectroscopy, elemental analysis and DFT calculations. In all three complexes, a ligand (L1) is coordinated in a deprotonated formally neutral zwitterionic form via NNO donor set atoms. Cu(II) and Zn(II) form mononuclear penta-coordinated complexes [CuL1(N3)(CH3OH)]BF4 and [ZnL1(N3)2], respectively, while Mn(II) forms a binuclear [Mn2L12(μ-1,1-N3)2(N3)2]·2CH3OH complex, with unusual distorted trigonal-prismatic geometry around the metal centers. The antimicrobial activity of these complexes was tested against a panel of Gram-negative and Gram-positive bacteria, two yeasts and one fungal strain. The binuclear Mn(II) complex showed antifungal activity of similar intensity to amphotericin B. Based on the results of the brine shrimp test and DPPH radical scavenging activity, the most active Cu(II) and Mn(II) complexes were selected for evaluation of cytotoxic activity against five malignant cancer cell lines (HeLa, A375, MCF7, PC-3 and A549) and one normal cell line HaCaT. Both complexes showed significant activity. It should be pointed out that the activity of the Mn(II) complex against the MCF7 breast cancer cell line is only slightly weaker than that of cisplatin, but with selectivity to the tumor cell line in comparison to normal HaCaT cells, which is non-existent in the case of cisplatin.The supporting information for: Stevanović, Nevena, Zlatar, Matija, Novaković, Irena, Pevec, Andrej, Radanović, Dušanka, Matić, Ivana Z., Đorđić Crnogorac, Marija, Stanojković, Tatjana, Vujčić, Miroslava, Gruden, Maja, Sladić, Dušan, Anđelković, Katarina, Turel, Iztok, Čobeljić, Božidar, "Cu(II), Mn(II) and Zn(II) complexes of hydrazones with a quaternary ammonium moiety: synthesis, experimental and theoretical characterization and cytotoxic activity" in Dalton Transactions, 51, no. 1 (2022):185-196, [https://doi.org/10.1039/D1DT03169D]Published article: [https://cherry.chem.bg.ac.rs/handle/123456789/4857]Related crystallographic data (CCDC 2110386): [https://cherry.chem.bg.ac.rs/handle/123456789/4859]Related crystallographic data (CCDC 2110387): [https://cherry.chem.bg.ac.rs/handle/123456789/4860]Related crystallographic data (CCDC 2110388): [https://cherry.chem.bg.ac.rs/handle/123456789/4861

Supplementary data for article: Pantelić, N.; Zmejkovski, B. B.; Kolundžija, B.; Crnogorac, M. Đ.; Vujić, J. M.; Dojčinović, B.; Trifunović, S. R.; Stanojković, T. P.; Sabo, T. J.; Kaluđerović, G. N. In Vitro Antitumor Activity, Metal Uptake and Reactivity with Ascorbic Acid and BSA of Some Gold(III) Complexes with N,N′-Ethylenediamine Bidentate Ester Ligands. Journal of Inorganic Biochemistry 2017, 172, 55–66. https://doi.org/10.1016/j.jinorgbio.2017.04.001

Supplementary material for: [https://doi.org/10.1016/j.jinorgbio.2017.04.001]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2478]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3070

Supplementary data for the article: Stevanović, N.; Mazzeo, P. P.; Bacchi, A.; Matić, I. Z.; Đorđić Crnogorac, M.; Stanojković, T.; Vujčić, M.; Novaković, I.; Radanović, D.; Šumar-Ristović, M.; Sladić, D.; Čobeljić, B.; Anđelković, K. Synthesis, Characterization, Antimicrobial and Cytotoxic Activity and DNA-Binding Properties of d-Metal Complexes with Hydrazones of Girard’s T and P Reagents. J Biol Inorg Chem 2021. https://doi.org/10.1007/s00775-021-01893-5.

In this work synthesis, characterization and crystal structures of 1, Zn(II) complex ([ZnL1(NCS)2]), with (E)-1-(2-oxo-2-(2-(quinolin-2-ylmethylene)hydrazinyl)ethyl)pyridin-1-ium chloride (HL1Cl) and 2, Bi(III) complex ([BiHL2Cl4] × 1/2CH3OH), with (E)-N,N,N-trimethyl-2-oxo-2-(2-(1-(thiazol-2-yl)ethylidene)hydrazinyl)ethan-1-aminium chloride (HL2Cl), have been reported. Zn(II) complex possesses a distorted trigonal bipyramidal geometry while surroundings around Bi(III) ion are extended pentagonal bipyramidal. Antimicrobial activity, brine shrimp assay and DPPH radical scavenging activity of both complexes, including previously synthesized complexes with HL2Cl ligand (Zn(II) and Ni(II)) and complexes with (E)-N,N,N-trimethyl-2-oxo-2-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)ethan-1-aminium chloride (HL3Cl) (Zn(II), Cu(II), Cd(II), Co(II), Fe(III), Ni(II)), were evaluated. For the most active complexes, cytotoxic activity against five malignant cancer cell lines (HeLa, A375, MCF7, PC-3 and A549) and normal cell line HaCaT, as well as generation of reactive oxygen species (ROS), was tested.Supplementary material for: [https://doi.org/10.1007/s00775-021-01893-5]Related to published version: [https://cherry.chem.bg.ac.rs/handle/123456789/4673

Evaluation of cytokine expression and circulating immune cell subsets as potential parameters of acute radiation toxicity in prostate cancer patients

One of the challenges of radiation oncology in the era of personalized medicine is identification of biomarkers associated with individual radiosensitivity. The aim of research was to evaluate the possible clinical value of the associations between clinical, physical, and biological factors, and risk for development of acute radiotoxicity in patients with prostate cancer. The study involved forty four patients treated with three-dimensional conformal radiotherapy. The concentrations of IL-1β, IL-2, IL-6, IFN-γ and TGF-β1 were assessed before radiotherapy, after 5th, 15th and 25th radiotherapy fractions, at the end, and 1 month after the end of radiotherapy. Cytokine gene expression was determined in peripheral blood mononuclear cells. The univariate analysis of circulating cytokine levels during radiotherapy showed that increased serum concentrations of IL-6 were significantly associated with higher grade of acute genitourinary toxicity. The multivariate analysis demonstrated that increased level of IL-6 during the radiotherapy was significantly associated with higher grade of acute genitourinary toxicity across treatment. TGF-β expression levels significantly decreased during course of radiotherapy. Research indicates that changes in circulating cytokine levels might be important parameter of radiotoxicity in patients with prostate cancer. These findings suggest that future studies based on multi-parameter examination are necessary for prediction of individual radiosensitivity