TY  - JOUR
AU  - Pavlović, Radoslav Z.
AU  - Finnegan, Tyler J.
AU  - Metlushko, Anna
AU  - Hansen, Alexandar L.
AU  - Waudby, Christopher A.
AU  - Wang, Xiuze
AU  - Hoefer, Nicole
AU  - McComb, David W.
AU  - Pavić, Aleksandar
AU  - Plackić, Nikola
AU  - Novaković, Jovana
AU  - Bradić, Jovana
AU  - Jeremić, Nevena
AU  - Jakovljević, Vladimir
AU  - Šmit, Biljana
AU  - Matić, Sanja
AU  - Alvarez-Saavedra, Matias A.
AU  - Čapo, Ivan
AU  - Moore, Curtis E.
AU  - Stupp, Samuel I.
AU  - Badjić, Jovica D.
PY  - 2023
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.202303374
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2280
AB  - We describe the preparation, dynamic, assembly characteristics of vase-shaped basket 13− along with its ability to form an inclusion complex with anticancer drug mitoxantrone in abiotic and biotic systems. This novel cavitand has a deep nonpolar pocket consisting of three naphthalimide sides fused to a bicyclic platform at the bottom while carrying polar glycines at the top. The results of 1H Nuclear Magnetic Resonance (NMR), 1H NMR Chemical Exchange Saturation Transfer (CEST), Calorimetry, Hybrid Replica Exchange Molecular Dynamics (REMD), and Microcrystal Electron Diffraction (MicroED) measurements are in line with 1 forming dimer [12]6−, to be in equilibrium with monomers 1(R)3− (relaxed) and 1(S)3− (squeezed). Through simultaneous line-shape analysis of 1H NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket 1(R)3− includes anticancer drug mitoxantrone (MTO2+) in its pocket to give stable binary complex [MTO⊂1]− (Kd=2.1 μM) that can be precipitated in vitro with UV light or pH as stimuli. Both in vitro and in vivo studies showed that the basket is nontoxic, while at a higher proportion with respect to MTO it reduced its cytotoxicity in vitro. With well-characterized internal dynamics and dimerization, the ability to include mitoxantrone, and biocompatibility, the stage is set to develop sequestering agents from deep-cavity baskets.
T2  - Chemistry – A European Journal
T1  - Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems
IS  - 68
SP  - e202303374
VL  - 29
DO  - 10.1002/chem.202303374
ER  - 

@article{
author = "Pavlović, Radoslav Z. and Finnegan, Tyler J. and Metlushko, Anna and Hansen, Alexandar L. and Waudby, Christopher A. and Wang, Xiuze and Hoefer, Nicole and McComb, David W. and Pavić, Aleksandar and Plackić, Nikola and Novaković, Jovana and Bradić, Jovana and Jeremić, Nevena and Jakovljević, Vladimir and Šmit, Biljana and Matić, Sanja and Alvarez-Saavedra, Matias A. and Čapo, Ivan and Moore, Curtis E. and Stupp, Samuel I. and Badjić, Jovica D.",
year = "2023",
abstract = "We describe the preparation, dynamic, assembly characteristics of vase-shaped basket 13− along with its ability to form an inclusion complex with anticancer drug mitoxantrone in abiotic and biotic systems. This novel cavitand has a deep nonpolar pocket consisting of three naphthalimide sides fused to a bicyclic platform at the bottom while carrying polar glycines at the top. The results of 1H Nuclear Magnetic Resonance (NMR), 1H NMR Chemical Exchange Saturation Transfer (CEST), Calorimetry, Hybrid Replica Exchange Molecular Dynamics (REMD), and Microcrystal Electron Diffraction (MicroED) measurements are in line with 1 forming dimer [12]6−, to be in equilibrium with monomers 1(R)3− (relaxed) and 1(S)3− (squeezed). Through simultaneous line-shape analysis of 1H NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket 1(R)3− includes anticancer drug mitoxantrone (MTO2+) in its pocket to give stable binary complex [MTO⊂1]− (Kd=2.1 μM) that can be precipitated in vitro with UV light or pH as stimuli. Both in vitro and in vivo studies showed that the basket is nontoxic, while at a higher proportion with respect to MTO it reduced its cytotoxicity in vitro. With well-characterized internal dynamics and dimerization, the ability to include mitoxantrone, and biocompatibility, the stage is set to develop sequestering agents from deep-cavity baskets.",
journal = "Chemistry – A European Journal",
title = "Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems",
number = "68",
pages = "e202303374",
volume = "29",
doi = "10.1002/chem.202303374"
}

Pavlović, R. Z., Finnegan, T. J., Metlushko, A., Hansen, A. L., Waudby, C. A., Wang, X., Hoefer, N., McComb, D. W., Pavić, A., Plackić, N., Novaković, J., Bradić, J., Jeremić, N., Jakovljević, V., Šmit, B., Matić, S., Alvarez-Saavedra, M. A., Čapo, I., Moore, C. E., Stupp, S. I.,& Badjić, J. D.. (2023). Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems. in Chemistry – A European Journal, 29(68), e202303374.
https://doi.org/10.1002/chem.202303374

Pavlović RZ, Finnegan TJ, Metlushko A, Hansen AL, Waudby CA, Wang X, Hoefer N, McComb DW, Pavić A, Plackić N, Novaković J, Bradić J, Jeremić N, Jakovljević V, Šmit B, Matić S, Alvarez-Saavedra MA, Čapo I, Moore CE, Stupp SI, Badjić JD. Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems. in Chemistry – A European Journal. 2023;29(68):e202303374.
doi:10.1002/chem.202303374 .

Pavlović, Radoslav Z., Finnegan, Tyler J., Metlushko, Anna, Hansen, Alexandar L., Waudby, Christopher A., Wang, Xiuze, Hoefer, Nicole, McComb, David W., Pavić, Aleksandar, Plackić, Nikola, Novaković, Jovana, Bradić, Jovana, Jeremić, Nevena, Jakovljević, Vladimir, Šmit, Biljana, Matić, Sanja, Alvarez-Saavedra, Matias A., Čapo, Ivan, Moore, Curtis E., Stupp, Samuel I., Badjić, Jovica D., "Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems" in Chemistry – A European Journal, 29, no. 68 (2023):e202303374,
https://doi.org/10.1002/chem.202303374 . .

TY  - JOUR
AU  - Stojanović, Aleksandra
AU  - Veselinović, Mirjana
AU  - Zong, Yanan
AU  - Jakovljević, Vladimir
AU  - Pruner, Iva
AU  - Antović, Aleksandra
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1454
AB  - This study sought to identify different subpopulations of extracellular vesicles (EVs) in plasma from female patients with established rheumatoid arthritis (RA) in relation to the activation of coagulation and fibrin formation in these patients. Forty women were included in the study, 20 patients and 20 age-matched healthy controls. The mean disease duration in patients was 13.0 (5.0-25.0) years, with medium to high disease activity despite ongoing treatment with low-dose prednisolone and methotrexate. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. The concentration of phosphatidylserine-positive (PS+) EVs; platelet (CD42a(+)), leucocyte (CD45(+)), monocyte (CD14(+)), and endothelial (CD144(+))-derived EVs; and EVs-expressing tissue factor (CD142(+)), P-selectin (CD62P(+)), and E-selectin (CD62E(+)) were determined by flow cytometry analysis. Overall hemostasis potential (OHP) was assessed to follow the hemostatic disturbances, including the parameters for overall coagulation potential (OCP) and overall fibrinolytic potential (OFP). Fibrin clot turbidity was measured together with clot lysis time, and scanning electron microscopy was performed. Increased concentrations of PS+, CD42a(+), CD142(+), CD45(+), CD14(+), and CD62P(+) EVs were found in plasma from patients with RA compared to healthy controls, and the concentrations of PS+, CD42a(+), CD14(+), and CD62P(+) EVs were positively correlated with the inflammatory parameters in RA patients. Positive correlations were also found between the levels of PS+ and CD42a(+) EVs and OCP as well as between the levels of PS+, CD42a(+), and CD62P(+)EVs and OHP. The levels of PS+, CD42a(+), CD14(+), CD62P(+), and CD62E(+) EVs were negatively correlated with OFP. Elevated levels of circulating EVs of different cell origins were found in patients with established RA, in relation to the inflammatory burden and coagulation activation in the disease.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Immunology
T1  - Increased Expression of Extracellular Vesicles Is Associated With the Procoagulant State in Patients With Established Rheumatoid Arthritis
VL  - 12
DO  - 10.3389/fimmu.2021.718845
ER  - 

@article{
author = "Stojanović, Aleksandra and Veselinović, Mirjana and Zong, Yanan and Jakovljević, Vladimir and Pruner, Iva and Antović, Aleksandra",
year = "2021",
abstract = "This study sought to identify different subpopulations of extracellular vesicles (EVs) in plasma from female patients with established rheumatoid arthritis (RA) in relation to the activation of coagulation and fibrin formation in these patients. Forty women were included in the study, 20 patients and 20 age-matched healthy controls. The mean disease duration in patients was 13.0 (5.0-25.0) years, with medium to high disease activity despite ongoing treatment with low-dose prednisolone and methotrexate. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. The concentration of phosphatidylserine-positive (PS+) EVs; platelet (CD42a(+)), leucocyte (CD45(+)), monocyte (CD14(+)), and endothelial (CD144(+))-derived EVs; and EVs-expressing tissue factor (CD142(+)), P-selectin (CD62P(+)), and E-selectin (CD62E(+)) were determined by flow cytometry analysis. Overall hemostasis potential (OHP) was assessed to follow the hemostatic disturbances, including the parameters for overall coagulation potential (OCP) and overall fibrinolytic potential (OFP). Fibrin clot turbidity was measured together with clot lysis time, and scanning electron microscopy was performed. Increased concentrations of PS+, CD42a(+), CD142(+), CD45(+), CD14(+), and CD62P(+) EVs were found in plasma from patients with RA compared to healthy controls, and the concentrations of PS+, CD42a(+), CD14(+), and CD62P(+) EVs were positively correlated with the inflammatory parameters in RA patients. Positive correlations were also found between the levels of PS+ and CD42a(+) EVs and OCP as well as between the levels of PS+, CD42a(+), and CD62P(+)EVs and OHP. The levels of PS+, CD42a(+), CD14(+), CD62P(+), and CD62E(+) EVs were negatively correlated with OFP. Elevated levels of circulating EVs of different cell origins were found in patients with established RA, in relation to the inflammatory burden and coagulation activation in the disease.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Immunology",
title = "Increased Expression of Extracellular Vesicles Is Associated With the Procoagulant State in Patients With Established Rheumatoid Arthritis",
volume = "12",
doi = "10.3389/fimmu.2021.718845"
}

Stojanović, A., Veselinović, M., Zong, Y., Jakovljević, V., Pruner, I.,& Antović, A.. (2021). Increased Expression of Extracellular Vesicles Is Associated With the Procoagulant State in Patients With Established Rheumatoid Arthritis. in Frontiers in Immunology
Frontiers Media Sa, Lausanne., 12.
https://doi.org/10.3389/fimmu.2021.718845

Stojanović A, Veselinović M, Zong Y, Jakovljević V, Pruner I, Antović A. Increased Expression of Extracellular Vesicles Is Associated With the Procoagulant State in Patients With Established Rheumatoid Arthritis. in Frontiers in Immunology. 2021;12.
doi:10.3389/fimmu.2021.718845 .

Stojanović, Aleksandra, Veselinović, Mirjana, Zong, Yanan, Jakovljević, Vladimir, Pruner, Iva, Antović, Aleksandra, "Increased Expression of Extracellular Vesicles Is Associated With the Procoagulant State in Patients With Established Rheumatoid Arthritis" in Frontiers in Immunology, 12 (2021),
https://doi.org/10.3389/fimmu.2021.718845 . .

TY  - JOUR
AU  - Petković, Anica
AU  - Al-Khalili, Faris
AU  - Antović, Aleksandra
AU  - Ammar, Majeed
AU  - Pruner, Iva
AU  - Vranić, Aleksandra
AU  - Soutari, Nida
AU  - Zdravković, Nebojša
AU  - Malmstrom, Rickard E.
AU  - Jakovljević, Vladimir
AU  - Antović, Jovan P.
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1345
AB  - The study was aimed to evaluate the effects of two standard doses of rivaroxaban and dabigatran on global hemostatic assays in patients with atrial fibrillation. The study included 52 patients treated with rivaroxaban (15/20 mg), 50 on dabigatran (110/150 mg) and 20 healthy individuals. Platelet-poor plasma was used for determination of three global hemostatic assays, namely endogenous thrombin potential (ETP), calibrated automated thrombogram (CAT) and overall hemostasis potential (OHP). Rivaroxaban and dabigatran reduced ETP (P lt 0.01) although OHP (P lt 0.05) was diminished only by dabigatran. Strong correlations were noticed between ETP parameters and the plasma concentrations of rivaroxaban (ETP, rUS0.51; c-max, rUS0.85; t-lag, rU0.83; t-max, rU0.66) as well as with plasma concentration of dabigatran (ETP, rUS0.75; c-max, rUS0.74; t-lag, rU0.73; t-max, rU0.52). Analysis of dabigatran concentrations under 50 ng/ml showed that ETP parameter has area under the concentration-time curvereceiver operating characteristic value of 0.879 (95% confidence interval 0.776-0.980). Dabigatran treatment paradoxically increased area under the concentration-time curve and peak values although rivaroxaban decreased peak values (P lt 0.01). However, significant correlation between CAT parameters and plasma concentration of both direct oral anticoagulants was not observed. We confirmed that the CAT assay is inappropriate for estimation of dabigatran effects and is not fully sensitive as regards rivaroxaban. The ETP assay can potentially be the appropriate method for estimation of global hemostatic capacity as regards both direct oral anticoagulants. The role of OHP needs to be confirmed in additional studies. ETP parameter of chromogenic assay has promising potential in exclusion of high plasma concentrations of dabigatran.
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Blood Coagulation & Fibrinolysis
T1  - Effects of rivaroxaban and dabigatran on global hemostasis in patients with atrial fibrillation
EP  - 252
IS  - 4
SP  - 243
VL  - 31
DO  - 10.1097/MBC.0000000000000907
ER  - 

@article{
author = "Petković, Anica and Al-Khalili, Faris and Antović, Aleksandra and Ammar, Majeed and Pruner, Iva and Vranić, Aleksandra and Soutari, Nida and Zdravković, Nebojša and Malmstrom, Rickard E. and Jakovljević, Vladimir and Antović, Jovan P.",
year = "2020",
abstract = "The study was aimed to evaluate the effects of two standard doses of rivaroxaban and dabigatran on global hemostatic assays in patients with atrial fibrillation. The study included 52 patients treated with rivaroxaban (15/20 mg), 50 on dabigatran (110/150 mg) and 20 healthy individuals. Platelet-poor plasma was used for determination of three global hemostatic assays, namely endogenous thrombin potential (ETP), calibrated automated thrombogram (CAT) and overall hemostasis potential (OHP). Rivaroxaban and dabigatran reduced ETP (P lt 0.01) although OHP (P lt 0.05) was diminished only by dabigatran. Strong correlations were noticed between ETP parameters and the plasma concentrations of rivaroxaban (ETP, rUS0.51; c-max, rUS0.85; t-lag, rU0.83; t-max, rU0.66) as well as with plasma concentration of dabigatran (ETP, rUS0.75; c-max, rUS0.74; t-lag, rU0.73; t-max, rU0.52). Analysis of dabigatran concentrations under 50 ng/ml showed that ETP parameter has area under the concentration-time curvereceiver operating characteristic value of 0.879 (95% confidence interval 0.776-0.980). Dabigatran treatment paradoxically increased area under the concentration-time curve and peak values although rivaroxaban decreased peak values (P lt 0.01). However, significant correlation between CAT parameters and plasma concentration of both direct oral anticoagulants was not observed. We confirmed that the CAT assay is inappropriate for estimation of dabigatran effects and is not fully sensitive as regards rivaroxaban. The ETP assay can potentially be the appropriate method for estimation of global hemostatic capacity as regards both direct oral anticoagulants. The role of OHP needs to be confirmed in additional studies. ETP parameter of chromogenic assay has promising potential in exclusion of high plasma concentrations of dabigatran.",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Blood Coagulation & Fibrinolysis",
title = "Effects of rivaroxaban and dabigatran on global hemostasis in patients with atrial fibrillation",
pages = "252-243",
number = "4",
volume = "31",
doi = "10.1097/MBC.0000000000000907"
}

Petković, A., Al-Khalili, F., Antović, A., Ammar, M., Pruner, I., Vranić, A., Soutari, N., Zdravković, N., Malmstrom, R. E., Jakovljević, V.,& Antović, J. P.. (2020). Effects of rivaroxaban and dabigatran on global hemostasis in patients with atrial fibrillation. in Blood Coagulation & Fibrinolysis
Lippincott Williams & Wilkins, Philadelphia., 31(4), 243-252.
https://doi.org/10.1097/MBC.0000000000000907

Petković A, Al-Khalili F, Antović A, Ammar M, Pruner I, Vranić A, Soutari N, Zdravković N, Malmstrom RE, Jakovljević V, Antović JP. Effects of rivaroxaban and dabigatran on global hemostasis in patients with atrial fibrillation. in Blood Coagulation & Fibrinolysis. 2020;31(4):243-252.
doi:10.1097/MBC.0000000000000907 .

Petković, Anica, Al-Khalili, Faris, Antović, Aleksandra, Ammar, Majeed, Pruner, Iva, Vranić, Aleksandra, Soutari, Nida, Zdravković, Nebojša, Malmstrom, Rickard E., Jakovljević, Vladimir, Antović, Jovan P., "Effects of rivaroxaban and dabigatran on global hemostasis in patients with atrial fibrillation" in Blood Coagulation & Fibrinolysis, 31, no. 4 (2020):243-252,
https://doi.org/10.1097/MBC.0000000000000907 . .

TY  - JOUR
AU  - Vranić, Aleksandra
AU  - Pruner, Iva
AU  - Veselinović, Mirjana
AU  - Soutari, Nida
AU  - Petković, Anica
AU  - Jakovljević, Vladimir
AU  - Antović, Aleksandra
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1230
AB  - Objectives This study was aimed to assess hemostatic disturbances in female patients with established rheumatoid arthritis (RA) in relation to menopausal status and disease activity. Method Ninety women were included in the study, 42 patients and 48 age-matched healthy controls. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. Two global hemostatic assays were employed, namely endogenous thrombin potential (ETP) and overall hemostasis potential (OHP). The parameters of the ETP assay (ETP, C-max, t-lag, t-max) and OHP assay (overall coagulation potential (OCP) and overall fibrinolytic potential (OFP)) were assessed. Moreover, the parameters of the fibrin clot (lag time, Max Abs, and slope) were measured by clot turbidity and scanning electron microscopy (SEM). Both patients and controls were divided into four subgroups according to menopause status. Results The premenopausal controls differed significantly from all other subgroups in terms of diminished levels of ETP (p = 0.02), C-max (p = 0.01), OCP (p = 0.02), OHP (p = 0.001), and Max Abs (p = 0.008), while OFP (p = 0.0001) was increased. This tendency was not seen in the premenopausal RA patients compared with the postmenopausal RA patients. SEM images showed denser clots composed of thinner fibers in samples from RA patients. The disease activity measured by DAS28 correlated with OCP and OHP (r = 0.54; p = 0.001 and r = 0.44; p = 0.003, respectively) indicating persistent hypercoagulable condition in the whole group of RA patients. Conclusions Our results point towards coagulation activation in premenopausal women with established RA. The patients were well characterized, which enabled assessment in a real-life setting.
PB  - Springer London Ltd, London
T2  - Clinical Rheumatology
T1  - Assessment of hemostatic disturbances in women with established rheumatoid arthritis
EP  - 3014
IS  - 11
SP  - 3005
VL  - 38
DO  - 10.1007/s10067-019-04629-8
ER  - 

@article{
author = "Vranić, Aleksandra and Pruner, Iva and Veselinović, Mirjana and Soutari, Nida and Petković, Anica and Jakovljević, Vladimir and Antović, Aleksandra",
year = "2019",
abstract = "Objectives This study was aimed to assess hemostatic disturbances in female patients with established rheumatoid arthritis (RA) in relation to menopausal status and disease activity. Method Ninety women were included in the study, 42 patients and 48 age-matched healthy controls. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. Two global hemostatic assays were employed, namely endogenous thrombin potential (ETP) and overall hemostasis potential (OHP). The parameters of the ETP assay (ETP, C-max, t-lag, t-max) and OHP assay (overall coagulation potential (OCP) and overall fibrinolytic potential (OFP)) were assessed. Moreover, the parameters of the fibrin clot (lag time, Max Abs, and slope) were measured by clot turbidity and scanning electron microscopy (SEM). Both patients and controls were divided into four subgroups according to menopause status. Results The premenopausal controls differed significantly from all other subgroups in terms of diminished levels of ETP (p = 0.02), C-max (p = 0.01), OCP (p = 0.02), OHP (p = 0.001), and Max Abs (p = 0.008), while OFP (p = 0.0001) was increased. This tendency was not seen in the premenopausal RA patients compared with the postmenopausal RA patients. SEM images showed denser clots composed of thinner fibers in samples from RA patients. The disease activity measured by DAS28 correlated with OCP and OHP (r = 0.54; p = 0.001 and r = 0.44; p = 0.003, respectively) indicating persistent hypercoagulable condition in the whole group of RA patients. Conclusions Our results point towards coagulation activation in premenopausal women with established RA. The patients were well characterized, which enabled assessment in a real-life setting.",
publisher = "Springer London Ltd, London",
journal = "Clinical Rheumatology",
title = "Assessment of hemostatic disturbances in women with established rheumatoid arthritis",
pages = "3014-3005",
number = "11",
volume = "38",
doi = "10.1007/s10067-019-04629-8"
}

Vranić, A., Pruner, I., Veselinović, M., Soutari, N., Petković, A., Jakovljević, V.,& Antović, A.. (2019). Assessment of hemostatic disturbances in women with established rheumatoid arthritis. in Clinical Rheumatology
Springer London Ltd, London., 38(11), 3005-3014.
https://doi.org/10.1007/s10067-019-04629-8

Vranić A, Pruner I, Veselinović M, Soutari N, Petković A, Jakovljević V, Antović A. Assessment of hemostatic disturbances in women with established rheumatoid arthritis. in Clinical Rheumatology. 2019;38(11):3005-3014.
doi:10.1007/s10067-019-04629-8 .

Vranić, Aleksandra, Pruner, Iva, Veselinović, Mirjana, Soutari, Nida, Petković, Anica, Jakovljević, Vladimir, Antović, Aleksandra, "Assessment of hemostatic disturbances in women with established rheumatoid arthritis" in Clinical Rheumatology, 38, no. 11 (2019):3005-3014,
https://doi.org/10.1007/s10067-019-04629-8 . .

TY  - JOUR
AU  - Vučićević, Ksenija
AU  - Jakovljević, Vladimir
AU  - Čolović, Nataša
AU  - Tošić, Nataša
AU  - Kostić, Tatjana
AU  - Glumac, Irena
AU  - Pavlović, Sonja
AU  - Karan-Đurašević, Teodora
AU  - Čolović, Milica
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/982
AB  - Uvod: Rezistencija na apoptozu koja karakteriše maligne B limfocite in vivo u hroničnoj limfocitnoj leukemiji (HLL) delimično je uzrokovana unutrašnjim poremecajima apoptotske mašinerije u ovim celijama. Ti poremecaji su rezultat genetičkih promena i aberantne ekspresije regulatora procesa apoptoze, među kojima ključnu ulogu imaju članovi Bcl2 familije. Cilj: Cilj ove studije je bio da se ispita udruženost nivoa ekspresije proapoptotskog Bax gena, kao i Bcl2/Bax odnosa, sa kliničkim karakteristikama bolesnika sa HLL kao i molekularnim prognostičkim markerima, i to mutacionim statusom rearanžiranih gena za teške lance imunoglobulina (IGHV) i ekspresijom gena za lipoproteinsku lipazu (LPL). Metode: Analizirana je ekspresija Bax iRNK i Bcl2/Bax iRNK odnos u mononuklearnim celijama periferne krvi 58 bolesnika sa HLL i 10 zdravih kontrola metodom reverzne transkripcije i lančane reakcije polimeraze u realnom vremenu (qRT-PCR). Rezultati: Detektovana je povišena ekspresija Bax gena u HLL uzorcima u odnosu na kontrolne uzorke (p=0,003), kao i povišen Bcl2/Bax odnos (p= lt 0,001). Kada je u pitanju udruženost sa prognostičkim markerima, Bcl2/Bax odnos je ispoljio negativnu korelaciju sa vremenom udvostručavanja broja limfocita (r=-0,307; p=0,0451), dok je visoka ekspresija Bax bila povezana sa LPL-pozitivnim statusom (p=0,035). I ekspresija Bax gena i Bcl2/Bax odnos su bili viši kod bolesnika sa nemutiranim u odnosu na bolesnike sa mutiranim IGHV genima, ali nije dostignuta statistička značajnost. Zaključak: Rezultati ove studije ukazuju na mogucu ulogu poremecene ekspresije Bcl2 i Bax gena, koja dovodi do visokog Bcl2/Bax odnosa u leukemijskim celijama, u patogenezi i kliničkom toku HLL.
AB  - Background: In chronic lymphocytic leukemia (CLL), in vivo apoptotic resistance of malignant B lymphocytes results, in part, from the intrinsic defects of their apoptotic machinery. These include genetic alterations and aberrant expression of many apoptosis regulators, among which the Bcl2 family members play a central role. Aim: The aim of this study was to investigate the association of pro-apoptotic Bax gene expression and Bcl2/Bax ratio with the clinical features of CLL patients as well as with molecular prognostic markers, namely the mutational status of rearranged immunoglobulin heavy variable (IGHV) genes and lipoprotein lipase (LPL) gene expression. Methods: We analyzed the expression of Bax mRNA and Bcl2/Bax mRNA ratio in the peripheral blood mononuclear cells of 58 unselected CLL patients and 10 healthy controls by the quantitative reverse-transcriptase polymerase chain reaction. Results: We detected significant Bax gene overexpression in CLL samples compared to non-leukemic samples (p=0.003), as well as an elevated Bcl2/Bax ratio (p= lt 0.001). Regarding the association with prognostic markers, the Bcl2/Bax ratio showed a negative correlation to lymphocyte doubling time (r=-0.307; p=0.0451), while high-level Bax expression was associated with LPL-positive status (p=0.035). Both the expression of Bax and Bcl2/Bax ratio were higher in patients with unmutated vs. mutated IGHV rearrangements, but this difference did not reach statistical significance. Conclusions: Our results suggest that dysregulated expression of Bcl2 and Bax, which leads to a high Bcl2/Bax ratio in leukemic cells, contributes to the pathogenesis and clinical course of CLL.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Udruženost ekspresije Bax gena i Bcl2/Bax odnosa sa kliničkim i molekularnim prognostičkim markerima u hroničnoj limfocitnoj leukemiji
T1  - Association of Bax expression and Bcl2/Bax ratio with clinical and molecular prognostic markers in chronic lymphocytic leukemia
EP  - 157
IS  - 2
SP  - 150
VL  - 35
DO  - 10.1515/jomb-2015-0017
ER  - 

@article{
author = "Vučićević, Ksenija and Jakovljević, Vladimir and Čolović, Nataša and Tošić, Nataša and Kostić, Tatjana and Glumac, Irena and Pavlović, Sonja and Karan-Đurašević, Teodora and Čolović, Milica",
year = "2016",
abstract = "Uvod: Rezistencija na apoptozu koja karakteriše maligne B limfocite in vivo u hroničnoj limfocitnoj leukemiji (HLL) delimično je uzrokovana unutrašnjim poremecajima apoptotske mašinerije u ovim celijama. Ti poremecaji su rezultat genetičkih promena i aberantne ekspresije regulatora procesa apoptoze, među kojima ključnu ulogu imaju članovi Bcl2 familije. Cilj: Cilj ove studije je bio da se ispita udruženost nivoa ekspresije proapoptotskog Bax gena, kao i Bcl2/Bax odnosa, sa kliničkim karakteristikama bolesnika sa HLL kao i molekularnim prognostičkim markerima, i to mutacionim statusom rearanžiranih gena za teške lance imunoglobulina (IGHV) i ekspresijom gena za lipoproteinsku lipazu (LPL). Metode: Analizirana je ekspresija Bax iRNK i Bcl2/Bax iRNK odnos u mononuklearnim celijama periferne krvi 58 bolesnika sa HLL i 10 zdravih kontrola metodom reverzne transkripcije i lančane reakcije polimeraze u realnom vremenu (qRT-PCR). Rezultati: Detektovana je povišena ekspresija Bax gena u HLL uzorcima u odnosu na kontrolne uzorke (p=0,003), kao i povišen Bcl2/Bax odnos (p= lt 0,001). Kada je u pitanju udruženost sa prognostičkim markerima, Bcl2/Bax odnos je ispoljio negativnu korelaciju sa vremenom udvostručavanja broja limfocita (r=-0,307; p=0,0451), dok je visoka ekspresija Bax bila povezana sa LPL-pozitivnim statusom (p=0,035). I ekspresija Bax gena i Bcl2/Bax odnos su bili viši kod bolesnika sa nemutiranim u odnosu na bolesnike sa mutiranim IGHV genima, ali nije dostignuta statistička značajnost. Zaključak: Rezultati ove studije ukazuju na mogucu ulogu poremecene ekspresije Bcl2 i Bax gena, koja dovodi do visokog Bcl2/Bax odnosa u leukemijskim celijama, u patogenezi i kliničkom toku HLL., Background: In chronic lymphocytic leukemia (CLL), in vivo apoptotic resistance of malignant B lymphocytes results, in part, from the intrinsic defects of their apoptotic machinery. These include genetic alterations and aberrant expression of many apoptosis regulators, among which the Bcl2 family members play a central role. Aim: The aim of this study was to investigate the association of pro-apoptotic Bax gene expression and Bcl2/Bax ratio with the clinical features of CLL patients as well as with molecular prognostic markers, namely the mutational status of rearranged immunoglobulin heavy variable (IGHV) genes and lipoprotein lipase (LPL) gene expression. Methods: We analyzed the expression of Bax mRNA and Bcl2/Bax mRNA ratio in the peripheral blood mononuclear cells of 58 unselected CLL patients and 10 healthy controls by the quantitative reverse-transcriptase polymerase chain reaction. Results: We detected significant Bax gene overexpression in CLL samples compared to non-leukemic samples (p=0.003), as well as an elevated Bcl2/Bax ratio (p= lt 0.001). Regarding the association with prognostic markers, the Bcl2/Bax ratio showed a negative correlation to lymphocyte doubling time (r=-0.307; p=0.0451), while high-level Bax expression was associated with LPL-positive status (p=0.035). Both the expression of Bax and Bcl2/Bax ratio were higher in patients with unmutated vs. mutated IGHV rearrangements, but this difference did not reach statistical significance. Conclusions: Our results suggest that dysregulated expression of Bcl2 and Bax, which leads to a high Bcl2/Bax ratio in leukemic cells, contributes to the pathogenesis and clinical course of CLL.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Udruženost ekspresije Bax gena i Bcl2/Bax odnosa sa kliničkim i molekularnim prognostičkim markerima u hroničnoj limfocitnoj leukemiji, Association of Bax expression and Bcl2/Bax ratio with clinical and molecular prognostic markers in chronic lymphocytic leukemia",
pages = "157-150",
number = "2",
volume = "35",
doi = "10.1515/jomb-2015-0017"
}

Vučićević, K., Jakovljević, V., Čolović, N., Tošić, N., Kostić, T., Glumac, I., Pavlović, S., Karan-Đurašević, T.,& Čolović, M.. (2016). Udruženost ekspresije Bax gena i Bcl2/Bax odnosa sa kliničkim i molekularnim prognostičkim markerima u hroničnoj limfocitnoj leukemiji. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 35(2), 150-157.
https://doi.org/10.1515/jomb-2015-0017

Vučićević K, Jakovljević V, Čolović N, Tošić N, Kostić T, Glumac I, Pavlović S, Karan-Đurašević T, Čolović M. Udruženost ekspresije Bax gena i Bcl2/Bax odnosa sa kliničkim i molekularnim prognostičkim markerima u hroničnoj limfocitnoj leukemiji. in Journal of Medical Biochemistry. 2016;35(2):150-157.
doi:10.1515/jomb-2015-0017 .

Vučićević, Ksenija, Jakovljević, Vladimir, Čolović, Nataša, Tošić, Nataša, Kostić, Tatjana, Glumac, Irena, Pavlović, Sonja, Karan-Đurašević, Teodora, Čolović, Milica, "Udruženost ekspresije Bax gena i Bcl2/Bax odnosa sa kliničkim i molekularnim prognostičkim markerima u hroničnoj limfocitnoj leukemiji" in Journal of Medical Biochemistry, 35, no. 2 (2016):150-157,
https://doi.org/10.1515/jomb-2015-0017 . .

TY  - JOUR
AU  - Vučićević, Ksenija
AU  - Jakovljević, Vladimir
AU  - Sretenović, Jasmina
AU  - Tošić, Nataša
AU  - Kostić, Tatjana
AU  - Glumac, Irena
AU  - Čolović, Milica
AU  - Čolović, Nataša
AU  - Pavlović, Sonja
AU  - Karan-Đurašević, Teodora
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/847
AB  - Hronična limfocitna leukemija (HLL) se manifestuje kao klonska ekspanzija zrelih B limfocita, čija se akumulacija pripisuje prvenstveno poremećajima procesa apoptoze. U HLL su uočene genetičke promene i aberantna ekspresija različitih članova Bcl2 genske familije, koji imaju ključnu ulogu u regulaciji unutrašnjeg, mitohondrijskog puta aktivacije apoptoze. U ovom radu je analizirana ekspresija anti-apoptotskog Bcl2 gena u grupi od 58 pacijenata obolelih od HLL. Metodom kvantitativnog RT-PCRa detektovana je povišena ekspresija Bcl2 mRNA u HLL uzorcima u odnosu na kontrolne uzorke (p= lt 0.001). 'Receiver operating characteristic' (ROC) analiza je pokazala da nivo ekspresije Bcl2 ima visoku moć diskriminacije između pacijenata i zdravih kontrola (A=0.98, 95% CI=0.95-1.009, p lt 0.0001).
AB  - Chronic lymphocytic leukaemia (CLL) manifests as clonal expansion of mature B lymphocytes, whose accumulation is primarily attributed to the dysregulation of apoptosis. Aberrant expression, as well as genetic alterations within various Bcl2 family members and central regulators of the intrinsic, mitochondriamediated apoptotic pathway all hasve been observed in CLL. Here, we report the expression analysis of the anti-apoptotic Bcl2 gene in a cohort of 58 CLL patients. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis revealed a significant overexpression of Bcl2 mRNA in CLL samples compared to control samples (p= lt 0.001). Receiver operating characteristic (ROC) analysis showed that the level of Bcl2 expression exerts a high discriminatory power between patients and healthy subjects (A=0.98, 95% CI=0.95-1.009, p lt 0.0001).
PB  - Univerzitet u Kragujevcu - Fakultet medicinskih nauka, Kragujevac
T2  - Serbian Journal of Experimental and Clinical Research
T1  - Ekspresija Bcl2 gena kod pacijenata sa hroničnom limfocitnom leukemijom
T1  - Expression of the Bcl2 gene in chronic lymphocytic leukaemia patients
EP  - 191
IS  - 3
SP  - 187
VL  - 16
DO  - 10.1515/SJECR-2015-0024
ER  - 

@article{
author = "Vučićević, Ksenija and Jakovljević, Vladimir and Sretenović, Jasmina and Tošić, Nataša and Kostić, Tatjana and Glumac, Irena and Čolović, Milica and Čolović, Nataša and Pavlović, Sonja and Karan-Đurašević, Teodora",
year = "2015",
abstract = "Hronična limfocitna leukemija (HLL) se manifestuje kao klonska ekspanzija zrelih B limfocita, čija se akumulacija pripisuje prvenstveno poremećajima procesa apoptoze. U HLL su uočene genetičke promene i aberantna ekspresija različitih članova Bcl2 genske familije, koji imaju ključnu ulogu u regulaciji unutrašnjeg, mitohondrijskog puta aktivacije apoptoze. U ovom radu je analizirana ekspresija anti-apoptotskog Bcl2 gena u grupi od 58 pacijenata obolelih od HLL. Metodom kvantitativnog RT-PCRa detektovana je povišena ekspresija Bcl2 mRNA u HLL uzorcima u odnosu na kontrolne uzorke (p= lt 0.001). 'Receiver operating characteristic' (ROC) analiza je pokazala da nivo ekspresije Bcl2 ima visoku moć diskriminacije između pacijenata i zdravih kontrola (A=0.98, 95% CI=0.95-1.009, p lt 0.0001)., Chronic lymphocytic leukaemia (CLL) manifests as clonal expansion of mature B lymphocytes, whose accumulation is primarily attributed to the dysregulation of apoptosis. Aberrant expression, as well as genetic alterations within various Bcl2 family members and central regulators of the intrinsic, mitochondriamediated apoptotic pathway all hasve been observed in CLL. Here, we report the expression analysis of the anti-apoptotic Bcl2 gene in a cohort of 58 CLL patients. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis revealed a significant overexpression of Bcl2 mRNA in CLL samples compared to control samples (p= lt 0.001). Receiver operating characteristic (ROC) analysis showed that the level of Bcl2 expression exerts a high discriminatory power between patients and healthy subjects (A=0.98, 95% CI=0.95-1.009, p lt 0.0001).",
publisher = "Univerzitet u Kragujevcu - Fakultet medicinskih nauka, Kragujevac",
journal = "Serbian Journal of Experimental and Clinical Research",
title = "Ekspresija Bcl2 gena kod pacijenata sa hroničnom limfocitnom leukemijom, Expression of the Bcl2 gene in chronic lymphocytic leukaemia patients",
pages = "191-187",
number = "3",
volume = "16",
doi = "10.1515/SJECR-2015-0024"
}

Vučićević, K., Jakovljević, V., Sretenović, J., Tošić, N., Kostić, T., Glumac, I., Čolović, M., Čolović, N., Pavlović, S.,& Karan-Đurašević, T.. (2015). Ekspresija Bcl2 gena kod pacijenata sa hroničnom limfocitnom leukemijom. in Serbian Journal of Experimental and Clinical Research
Univerzitet u Kragujevcu - Fakultet medicinskih nauka, Kragujevac., 16(3), 187-191.
https://doi.org/10.1515/SJECR-2015-0024

Vučićević K, Jakovljević V, Sretenović J, Tošić N, Kostić T, Glumac I, Čolović M, Čolović N, Pavlović S, Karan-Đurašević T. Ekspresija Bcl2 gena kod pacijenata sa hroničnom limfocitnom leukemijom. in Serbian Journal of Experimental and Clinical Research. 2015;16(3):187-191.
doi:10.1515/SJECR-2015-0024 .

Vučićević, Ksenija, Jakovljević, Vladimir, Sretenović, Jasmina, Tošić, Nataša, Kostić, Tatjana, Glumac, Irena, Čolović, Milica, Čolović, Nataša, Pavlović, Sonja, Karan-Đurašević, Teodora, "Ekspresija Bcl2 gena kod pacijenata sa hroničnom limfocitnom leukemijom" in Serbian Journal of Experimental and Clinical Research, 16, no. 3 (2015):187-191,
https://doi.org/10.1515/SJECR-2015-0024 . .