TY  - JOUR
AU  - Milovanović, Vera
AU  - Topić, Aleksandra
AU  - Milinković, Neda
AU  - Lazić, Zorica
AU  - Ivošević, Anita
AU  - Radojković, Dragica
AU  - Divac Rankov, Aleksandra
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4003
AB  - Objective: Chronic obstructive pulmonary disease (COPD) is multi-factorial disorder which
results from environmental influences and genetic factors. We aimed to investigate whether
methionine sulfoxide reductase A (MSRA) rs10903323 gene polymorphism is associated with
COPD development and severity in Serbian adult population.
Methods: The study included 155 patients with COPD and 134 healthy volunteers. Genotyping
was determined performing home-made polymerase chain reaction-restriction fragment length
polymorphism (PCR-RFLP). The difference between the inhibitory activities of normal and oxi-
dized Alpha-1-Antitrypsin (A1AT) against elastase and trypsin was used for determination of Oxi-
dized Alpha-1-Antitrypsin (OxyA1AT) (expressed as % and g/L). Functional activity of A1AT was
presented as a specific inhibitor activity to elastase (SIA-Elastase, kU/g).
Results: Frequencies of the genotypes AA, AG and GG were 80.0%, 20.0%, 0% in COPD patients
and 80.5%, 18.5% and 1.5% in the control group, and there was no significant difference in geno-
type or allele distributions between groups. Serum level of A1AT (g/L) and OxyA1AT was signifi-
cantly higher in COPD patients than in the control group, but functional activity of A1AT (SIA-
Elastase) was significantly lower in COPD patients than in the control group. In COPD group,
increased level of OxyA1ATwas present in G allele carriers who were smokers relative to G allele
carriers who were not smokers. In the smoker group of patients with severe and very severe
COPD (GOLD3+4), significant increase in OxyA1AT level was present in G allele carriers compared to AA homozygotes.
Conclusion: These findings suggest that MSRA rs10903323 gene polymorphism is probably not a
risk for COPD by itself but could represent a COPD modifier, since minor, G allele, is associated with an increased level of oxidized A1AT, indicating impaired ability of MSRA to repair oxidized
A1AT in COPD-smokers, and in severe form of COPD.
PB  - Elsevier
T2  - Pulmonology
T1  - Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients
VL  - 30
IS  - 2
SP  - 122
EP  - 129
DO  - 10.1016/j.pulmoe.2021.09.003
ER  - 

@article{
author = "Milovanović, Vera and Topić, Aleksandra and Milinković, Neda and Lazić, Zorica and Ivošević, Anita and Radojković, Dragica and Divac Rankov, Aleksandra",
year = "2024",
abstract = "Objective: Chronic obstructive pulmonary disease (COPD) is multi-factorial disorder which
results from environmental influences and genetic factors. We aimed to investigate whether
methionine sulfoxide reductase A (MSRA) rs10903323 gene polymorphism is associated with
COPD development and severity in Serbian adult population.
Methods: The study included 155 patients with COPD and 134 healthy volunteers. Genotyping
was determined performing home-made polymerase chain reaction-restriction fragment length
polymorphism (PCR-RFLP). The difference between the inhibitory activities of normal and oxi-
dized Alpha-1-Antitrypsin (A1AT) against elastase and trypsin was used for determination of Oxi-
dized Alpha-1-Antitrypsin (OxyA1AT) (expressed as % and g/L). Functional activity of A1AT was
presented as a specific inhibitor activity to elastase (SIA-Elastase, kU/g).
Results: Frequencies of the genotypes AA, AG and GG were 80.0%, 20.0%, 0% in COPD patients
and 80.5%, 18.5% and 1.5% in the control group, and there was no significant difference in geno-
type or allele distributions between groups. Serum level of A1AT (g/L) and OxyA1AT was signifi-
cantly higher in COPD patients than in the control group, but functional activity of A1AT (SIA-
Elastase) was significantly lower in COPD patients than in the control group. In COPD group,
increased level of OxyA1ATwas present in G allele carriers who were smokers relative to G allele
carriers who were not smokers. In the smoker group of patients with severe and very severe
COPD (GOLD3+4), significant increase in OxyA1AT level was present in G allele carriers compared to AA homozygotes.
Conclusion: These findings suggest that MSRA rs10903323 gene polymorphism is probably not a
risk for COPD by itself but could represent a COPD modifier, since minor, G allele, is associated with an increased level of oxidized A1AT, indicating impaired ability of MSRA to repair oxidized
A1AT in COPD-smokers, and in severe form of COPD.",
publisher = "Elsevier",
journal = "Pulmonology",
title = "Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients",
volume = "30",
number = "2",
pages = "122-129",
doi = "10.1016/j.pulmoe.2021.09.003"
}

Milovanović, V., Topić, A., Milinković, N., Lazić, Z., Ivošević, A., Radojković, D.,& Divac Rankov, A.. (2024). Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients. in Pulmonology
Elsevier., 30(2), 122-129.
https://doi.org/10.1016/j.pulmoe.2021.09.003

Milovanović V, Topić A, Milinković N, Lazić Z, Ivošević A, Radojković D, Divac Rankov A. Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients. in Pulmonology. 2024;30(2):122-129.
doi:10.1016/j.pulmoe.2021.09.003 .

Milovanović, Vera, Topić, Aleksandra, Milinković, Neda, Lazić, Zorica, Ivošević, Anita, Radojković, Dragica, Divac Rankov, Aleksandra, "Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients" in Pulmonology, 30, no. 2 (2024):122-129,
https://doi.org/10.1016/j.pulmoe.2021.09.003 . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Milovanović, V.
AU  - Lazić, Z.
AU  - Ivošević, A.
AU  - Radojković, Dragica
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3134
AB  - Oxidative stress could reduce inhibitor activity of the alpha-1-antitrypsin (A1AT). Oxidative-modified A1AT (oxidized alpha-1-antitrypsin, OxyA1AT) significantly loses ability to protect the lungs from neutrophil elastase. We aimed to investigate OxyA1AT as a potential biomarker associated with onset and severity of chronic obstructive pulmonary disease (COPD) in adult population. The study included 65 patients with COPD (33 smokers and 32 no-smokers) and 46 healthy participants (17 smokers and 29 no-smokers). Determination of OxyA1AT in serum was based on the difference between the inhibitory activities of normal and oxidized A1AT against trypsin and elastase. The level of OxyA1AT was significantly increased in the group of COPD smokers compared to healthy no-smokers (p = 0.030) and COPD no-smokers (p = 0.009). The highest level of OxyA1AT was found in group of smokers with severe and very severe COPD in comparison to the following: no-smokers with the same stage of disease (p = 0.038), smokers with moderate COPD (p = 0.022), and the healthy control group, regardless of the smoking status (control no-smokers p = 0.001 and control smokers p = 0.034). In conclusion, serum level of OxyA1AT would be potentially good biomarker for the assessment of harmful effect of smoking to the onset and severity of COPD. Also, clinical significance of OxyA1AT as prognostic biomarker could be useful in assessing the effectiveness of antioxidant therapy for COPD and emphysema. Suitable and inexpensive laboratory method for determination of OxyA1AT is additional benefit for the introduction of OxyA1AT into routine clinical practice for diagnosis and monitoring of COPD.
PB  - Taylor & Francis Inc, Philadelphia
T2  - COPD-Journal of Chronic Obstructive Pulmonary Disease
T1  - Oxidized Alpha-1-Antitrypsin as a Potential Biomarker Associated with Onset and Severity of Chronic Obstructive Pulmonary Disease in Adult Population
VL  - 15
IS  - 5
SP  - 472
EP  - 478
DO  - 10.1080/15412555.2018.1541448
ER  - 

@article{
author = "Topić, Aleksandra and Milovanović, V. and Lazić, Z. and Ivošević, A. and Radojković, Dragica",
year = "2018",
abstract = "Oxidative stress could reduce inhibitor activity of the alpha-1-antitrypsin (A1AT). Oxidative-modified A1AT (oxidized alpha-1-antitrypsin, OxyA1AT) significantly loses ability to protect the lungs from neutrophil elastase. We aimed to investigate OxyA1AT as a potential biomarker associated with onset and severity of chronic obstructive pulmonary disease (COPD) in adult population. The study included 65 patients with COPD (33 smokers and 32 no-smokers) and 46 healthy participants (17 smokers and 29 no-smokers). Determination of OxyA1AT in serum was based on the difference between the inhibitory activities of normal and oxidized A1AT against trypsin and elastase. The level of OxyA1AT was significantly increased in the group of COPD smokers compared to healthy no-smokers (p = 0.030) and COPD no-smokers (p = 0.009). The highest level of OxyA1AT was found in group of smokers with severe and very severe COPD in comparison to the following: no-smokers with the same stage of disease (p = 0.038), smokers with moderate COPD (p = 0.022), and the healthy control group, regardless of the smoking status (control no-smokers p = 0.001 and control smokers p = 0.034). In conclusion, serum level of OxyA1AT would be potentially good biomarker for the assessment of harmful effect of smoking to the onset and severity of COPD. Also, clinical significance of OxyA1AT as prognostic biomarker could be useful in assessing the effectiveness of antioxidant therapy for COPD and emphysema. Suitable and inexpensive laboratory method for determination of OxyA1AT is additional benefit for the introduction of OxyA1AT into routine clinical practice for diagnosis and monitoring of COPD.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "COPD-Journal of Chronic Obstructive Pulmonary Disease",
title = "Oxidized Alpha-1-Antitrypsin as a Potential Biomarker Associated with Onset and Severity of Chronic Obstructive Pulmonary Disease in Adult Population",
volume = "15",
number = "5",
pages = "472-478",
doi = "10.1080/15412555.2018.1541448"
}

Topić, A., Milovanović, V., Lazić, Z., Ivošević, A.,& Radojković, D.. (2018). Oxidized Alpha-1-Antitrypsin as a Potential Biomarker Associated with Onset and Severity of Chronic Obstructive Pulmonary Disease in Adult Population. in COPD-Journal of Chronic Obstructive Pulmonary Disease
Taylor & Francis Inc, Philadelphia., 15(5), 472-478.
https://doi.org/10.1080/15412555.2018.1541448

Topić A, Milovanović V, Lazić Z, Ivošević A, Radojković D. Oxidized Alpha-1-Antitrypsin as a Potential Biomarker Associated with Onset and Severity of Chronic Obstructive Pulmonary Disease in Adult Population. in COPD-Journal of Chronic Obstructive Pulmonary Disease. 2018;15(5):472-478.
doi:10.1080/15412555.2018.1541448 .

Topić, Aleksandra, Milovanović, V., Lazić, Z., Ivošević, A., Radojković, Dragica, "Oxidized Alpha-1-Antitrypsin as a Potential Biomarker Associated with Onset and Severity of Chronic Obstructive Pulmonary Disease in Adult Population" in COPD-Journal of Chronic Obstructive Pulmonary Disease, 15, no. 5 (2018):472-478,
https://doi.org/10.1080/15412555.2018.1541448 . .

TY  - JOUR
AU  - Malić, Živka
AU  - Topić, Aleksandra
AU  - Francuski, Đorđe
AU  - Stanković, Marija
AU  - Nagorni-Obradović, Ljudmila
AU  - Marković, Bojan
AU  - Radojković, Dragica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2903
AB  - The genetic and non-genetic factors that contribute to the development of chronic obstructive pulmonary disease (COPD) are still poorly understood. We investigated the potential role of genetic variants of xenobiotic-metabolising enzymes (glutathione-S-transferase M1, GSTM1; glutathione-S-transferase T1, GSTT1; microsomal epoxide hydrolase, mEH), oxidative stress (assessed by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodG/creatinine), sex, ageing and smoking habits on susceptibility to development of COPD and its severity in Serbian population. The investigated population consisted of 153 healthy subjects (85 males and 68 females) and 71 patients with COPD (33 males and 38 females). Detection of GSTM1*null, GSTT1*null, mEH Tyr113His and mEH His139Arg gene variants was performed by PCR/RFLP method. Urinary 8-oxodG was determined using HPLC-MS/MS, and expressed as 8-oxodG/creatinine. We revealed that increased urinary 8-oxodG/creatinine and leucocytosis are the strongest independent predictors for COPD development. Increased level of oxidative stress increased the risk for COPD in males [odds ratio (OR), 95% confidence interval (CI): 8.42, 2.26-31.28], more than in females (OR, 95% CI: 3.60, 1.37-9.45). Additionally, independent predictors for COPD were ageing in males (OR, 95% CI: 1.29, 1.12-1.48), while in females they were at least one GSTM1 or GSTT1 gene deletion in combination (OR, 95% CI: 23.67, 2.62-213.46), and increased cumulative cigarette consumption (OR, 95% CI: 1.09, 1.01-1.16). Severity of COPD was associated with the combined effect of low mEH activity phenotype, high level of oxidative stress and heavy smoking. In conclusion, early identification of GSTM1*null or GSTT1*null genotypes in females, low mEH activity phenotype in heavy smokers and monitoring of oxidative stress level can be useful diagnostic and prognostic biomarkers.
PB  - Taylor & Francis Inc, Philadelphia
T2  - COPD-Journal of Chronic Obstructive Pulmonary Disease
T1  - Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults
VL  - 14
IS  - 1
SP  - 95
EP  - 104
DO  - 10.1080/15412555.2016.1199667
ER  - 

@article{
author = "Malić, Živka and Topić, Aleksandra and Francuski, Đorđe and Stanković, Marija and Nagorni-Obradović, Ljudmila and Marković, Bojan and Radojković, Dragica",
year = "2017",
abstract = "The genetic and non-genetic factors that contribute to the development of chronic obstructive pulmonary disease (COPD) are still poorly understood. We investigated the potential role of genetic variants of xenobiotic-metabolising enzymes (glutathione-S-transferase M1, GSTM1; glutathione-S-transferase T1, GSTT1; microsomal epoxide hydrolase, mEH), oxidative stress (assessed by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodG/creatinine), sex, ageing and smoking habits on susceptibility to development of COPD and its severity in Serbian population. The investigated population consisted of 153 healthy subjects (85 males and 68 females) and 71 patients with COPD (33 males and 38 females). Detection of GSTM1*null, GSTT1*null, mEH Tyr113His and mEH His139Arg gene variants was performed by PCR/RFLP method. Urinary 8-oxodG was determined using HPLC-MS/MS, and expressed as 8-oxodG/creatinine. We revealed that increased urinary 8-oxodG/creatinine and leucocytosis are the strongest independent predictors for COPD development. Increased level of oxidative stress increased the risk for COPD in males [odds ratio (OR), 95% confidence interval (CI): 8.42, 2.26-31.28], more than in females (OR, 95% CI: 3.60, 1.37-9.45). Additionally, independent predictors for COPD were ageing in males (OR, 95% CI: 1.29, 1.12-1.48), while in females they were at least one GSTM1 or GSTT1 gene deletion in combination (OR, 95% CI: 23.67, 2.62-213.46), and increased cumulative cigarette consumption (OR, 95% CI: 1.09, 1.01-1.16). Severity of COPD was associated with the combined effect of low mEH activity phenotype, high level of oxidative stress and heavy smoking. In conclusion, early identification of GSTM1*null or GSTT1*null genotypes in females, low mEH activity phenotype in heavy smokers and monitoring of oxidative stress level can be useful diagnostic and prognostic biomarkers.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "COPD-Journal of Chronic Obstructive Pulmonary Disease",
title = "Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults",
volume = "14",
number = "1",
pages = "95-104",
doi = "10.1080/15412555.2016.1199667"
}

Malić, Ž., Topić, A., Francuski, Đ., Stanković, M., Nagorni-Obradović, L., Marković, B.,& Radojković, D.. (2017). Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults. in COPD-Journal of Chronic Obstructive Pulmonary Disease
Taylor & Francis Inc, Philadelphia., 14(1), 95-104.
https://doi.org/10.1080/15412555.2016.1199667

Malić Ž, Topić A, Francuski Đ, Stanković M, Nagorni-Obradović L, Marković B, Radojković D. Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults. in COPD-Journal of Chronic Obstructive Pulmonary Disease. 2017;14(1):95-104.
doi:10.1080/15412555.2016.1199667 .

Malić, Živka, Topić, Aleksandra, Francuski, Đorđe, Stanković, Marija, Nagorni-Obradović, Ljudmila, Marković, Bojan, Radojković, Dragica, "Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults" in COPD-Journal of Chronic Obstructive Pulmonary Disease, 14, no. 1 (2017):95-104,
https://doi.org/10.1080/15412555.2016.1199667 . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Francuski, Đorđe
AU  - Nikolić, Aleksandra
AU  - Milošević, Katarina
AU  - Jovičić, Snežana
AU  - Marković, Bojan
AU  - Đukić, Mirjana
AU  - Radojković, Dragica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2833
AB  - Introduction: The significance of oxidative stress in pathogenesis of childhood asthma was recognized, but its role in the clinical manifestations of disease is still unclear. Materials and Methods: The study was conducted in 96 asthmatic children. The urinary biomarker of oxidative stress, 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG/creatinine) was determined by using HPLC-MS/MS. ELISA was performed to measure myeloperoxidase (MPO) and Cu,Zn-superoxide dismutase (Cu, Zn-SOD) in serum. Results: Logistic regression analysis revealed that female gender, tobacco smoke exposure, and increased 8-oxodG/creatinine were associated with risk for intermittent asthma, while the positive allergy test and increased Cu, Zn-SOD were associated with eczema in asthmatic children. Higher MPO (p = 0.033), and percent of granulocytes (p = 0.030) were found in severe persistent asthma in comparison to intermittent or mild persistent asthma. Conclusion: The main findings that TSE-induced oxidative stress is a risk for intermittent asthma and eczema may be clinically significant for the disease prevention and therapeutic improvements.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Fetal and Pediatric Pathology
T1  - The Role of Oxidative Stress in the Clinical Manifestations of Childhood Asthma
VL  - 36
IS  - 4
SP  - 294
EP  - 303
DO  - 10.1080/15513815.2017.1315199
ER  - 

@article{
author = "Topić, Aleksandra and Francuski, Đorđe and Nikolić, Aleksandra and Milošević, Katarina and Jovičić, Snežana and Marković, Bojan and Đukić, Mirjana and Radojković, Dragica",
year = "2017",
abstract = "Introduction: The significance of oxidative stress in pathogenesis of childhood asthma was recognized, but its role in the clinical manifestations of disease is still unclear. Materials and Methods: The study was conducted in 96 asthmatic children. The urinary biomarker of oxidative stress, 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG/creatinine) was determined by using HPLC-MS/MS. ELISA was performed to measure myeloperoxidase (MPO) and Cu,Zn-superoxide dismutase (Cu, Zn-SOD) in serum. Results: Logistic regression analysis revealed that female gender, tobacco smoke exposure, and increased 8-oxodG/creatinine were associated with risk for intermittent asthma, while the positive allergy test and increased Cu, Zn-SOD were associated with eczema in asthmatic children. Higher MPO (p = 0.033), and percent of granulocytes (p = 0.030) were found in severe persistent asthma in comparison to intermittent or mild persistent asthma. Conclusion: The main findings that TSE-induced oxidative stress is a risk for intermittent asthma and eczema may be clinically significant for the disease prevention and therapeutic improvements.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Fetal and Pediatric Pathology",
title = "The Role of Oxidative Stress in the Clinical Manifestations of Childhood Asthma",
volume = "36",
number = "4",
pages = "294-303",
doi = "10.1080/15513815.2017.1315199"
}

Topić, A., Francuski, Đ., Nikolić, A., Milošević, K., Jovičić, S., Marković, B., Đukić, M.,& Radojković, D.. (2017). The Role of Oxidative Stress in the Clinical Manifestations of Childhood Asthma. in Fetal and Pediatric Pathology
Taylor & Francis Inc, Philadelphia., 36(4), 294-303.
https://doi.org/10.1080/15513815.2017.1315199

Topić A, Francuski Đ, Nikolić A, Milošević K, Jovičić S, Marković B, Đukić M, Radojković D. The Role of Oxidative Stress in the Clinical Manifestations of Childhood Asthma. in Fetal and Pediatric Pathology. 2017;36(4):294-303.
doi:10.1080/15513815.2017.1315199 .

Topić, Aleksandra, Francuski, Đorđe, Nikolić, Aleksandra, Milošević, Katarina, Jovičić, Snežana, Marković, Bojan, Đukić, Mirjana, Radojković, Dragica, "The Role of Oxidative Stress in the Clinical Manifestations of Childhood Asthma" in Fetal and Pediatric Pathology, 36, no. 4 (2017):294-303,
https://doi.org/10.1080/15513815.2017.1315199 . .

TY  - JOUR
AU  - Ljujić, Mila
AU  - Mijatović, Sanja
AU  - Bulatović, Mirna Z.
AU  - Mojic, Marija
AU  - Maksimović-Ivanić, Danijela
AU  - Radojković, Dragica
AU  - Topić, Aleksandra
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2964
AB  - Increased circulating alpha-1-antitrypsin (AAT) correlates with cancer stage/aggressiveness, but its role in cancer biology is unclear. We revealed antagonistic effect of AAT to cisplatin-induced cytotoxicity in prostate (PC3) and melanoma (A375) cancer cell lines. Moreover, AAT abrogated cytotoxicity of MEK inhibitor U0126 in PC3 cell line. Weaker antagonistic effect of AAT on cytotoxicity of PI3/Akt and NF-kB inhibitors was also observed. In addition, cisplatin increased AAT gene expression in transfected PC3 cells. However, AAT derived from transfected PC3 cells did not antagonize cisplatin-induced cytotoxicity. In conclusion, these results suggest possible association between high circulating AAT and cisplatin resistance.
PB  - Springer, Dordrecht
T2  - Pathology & Oncology Research
T1  - Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines
VL  - 23
IS  - 2
SP  - 335
EP  - 343
DO  - 10.1007/s12253-016-0104-3
ER  - 

@article{
author = "Ljujić, Mila and Mijatović, Sanja and Bulatović, Mirna Z. and Mojic, Marija and Maksimović-Ivanić, Danijela and Radojković, Dragica and Topić, Aleksandra",
year = "2017",
abstract = "Increased circulating alpha-1-antitrypsin (AAT) correlates with cancer stage/aggressiveness, but its role in cancer biology is unclear. We revealed antagonistic effect of AAT to cisplatin-induced cytotoxicity in prostate (PC3) and melanoma (A375) cancer cell lines. Moreover, AAT abrogated cytotoxicity of MEK inhibitor U0126 in PC3 cell line. Weaker antagonistic effect of AAT on cytotoxicity of PI3/Akt and NF-kB inhibitors was also observed. In addition, cisplatin increased AAT gene expression in transfected PC3 cells. However, AAT derived from transfected PC3 cells did not antagonize cisplatin-induced cytotoxicity. In conclusion, these results suggest possible association between high circulating AAT and cisplatin resistance.",
publisher = "Springer, Dordrecht",
journal = "Pathology & Oncology Research",
title = "Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines",
volume = "23",
number = "2",
pages = "335-343",
doi = "10.1007/s12253-016-0104-3"
}

Ljujić, M., Mijatović, S., Bulatović, M. Z., Mojic, M., Maksimović-Ivanić, D., Radojković, D.,& Topić, A.. (2017). Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines. in Pathology & Oncology Research
Springer, Dordrecht., 23(2), 335-343.
https://doi.org/10.1007/s12253-016-0104-3

Ljujić M, Mijatović S, Bulatović MZ, Mojic M, Maksimović-Ivanić D, Radojković D, Topić A. Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines. in Pathology & Oncology Research. 2017;23(2):335-343.
doi:10.1007/s12253-016-0104-3 .

Ljujić, Mila, Mijatović, Sanja, Bulatović, Mirna Z., Mojic, Marija, Maksimović-Ivanić, Danijela, Radojković, Dragica, Topić, Aleksandra, "Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines" in Pathology & Oncology Research, 23, no. 2 (2017):335-343,
https://doi.org/10.1007/s12253-016-0104-3 . .

TY  - JOUR
AU  - Backović, Dragana
AU  - Ignjatović, Svetlana
AU  - Rakicević, Ljiljana
AU  - Novković, Mirjana
AU  - Kusić-Tisma, Jelena
AU  - Radojković, Dragica
AU  - Strugarević, Evgenija
AU  - Čalija, Branko
AU  - Radak, Đorđe
AU  - Kovac, Mirjana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2756
AB  - Objectives: A considerable number of patients do not achieve an adequate response to clopidogrel. Our study aimed to evaluate genetic and non-genetic factors as possible risks for clopidogrel high on-treatment platelet reactivity (HTPR) in patients (n=112) with carotid artery stenosis undergoing endarterectomy (CEA). Methods: Using multiple-electrode impedance aggregometry (MEA) the antiplatelet effectiveness of clopidogrel was measured after 24 h, 7 and 30 days of clopidogrel treatment, which was introduced after elective CEA at a dose of 75 mg daily, for at least 30 days. Results: HTPR was observed among 25% patients after clopidogrel therapy for 30 days. Further analysis showed that 53.3% of patients carrying the CYP2C19*2 gene variant had clopidogrel-HTPR, while in the wild type group there were 14.6% (p lt 0.001). Multivariate logistic regression analysis identified the CYP2C19*2 variant allele (OR 4.384; 95% CI 1.296-14.833, p=0.017) and high total cholesterol level (OR 2.090; 95% CI 1.263-3.459, p=0.004) as the only independent risk factors for clopidogrel-HTPR. Conclusion: The CYP2C19*2 gene variant and high total cholesterol level were major factors for clopidogrel-HTPR in patients with carotid artery stenosis undergoing CEA.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Current Vascular Pharmacology
T1  - Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study
VL  - 14
IS  - 6
SP  - 563
EP  - 569
DO  - 10.2174/1570161114666160714103148
ER  - 

@article{
author = "Backović, Dragana and Ignjatović, Svetlana and Rakicević, Ljiljana and Novković, Mirjana and Kusić-Tisma, Jelena and Radojković, Dragica and Strugarević, Evgenija and Čalija, Branko and Radak, Đorđe and Kovac, Mirjana",
year = "2016",
abstract = "Objectives: A considerable number of patients do not achieve an adequate response to clopidogrel. Our study aimed to evaluate genetic and non-genetic factors as possible risks for clopidogrel high on-treatment platelet reactivity (HTPR) in patients (n=112) with carotid artery stenosis undergoing endarterectomy (CEA). Methods: Using multiple-electrode impedance aggregometry (MEA) the antiplatelet effectiveness of clopidogrel was measured after 24 h, 7 and 30 days of clopidogrel treatment, which was introduced after elective CEA at a dose of 75 mg daily, for at least 30 days. Results: HTPR was observed among 25% patients after clopidogrel therapy for 30 days. Further analysis showed that 53.3% of patients carrying the CYP2C19*2 gene variant had clopidogrel-HTPR, while in the wild type group there were 14.6% (p lt 0.001). Multivariate logistic regression analysis identified the CYP2C19*2 variant allele (OR 4.384; 95% CI 1.296-14.833, p=0.017) and high total cholesterol level (OR 2.090; 95% CI 1.263-3.459, p=0.004) as the only independent risk factors for clopidogrel-HTPR. Conclusion: The CYP2C19*2 gene variant and high total cholesterol level were major factors for clopidogrel-HTPR in patients with carotid artery stenosis undergoing CEA.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Current Vascular Pharmacology",
title = "Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study",
volume = "14",
number = "6",
pages = "563-569",
doi = "10.2174/1570161114666160714103148"
}

Backović, D., Ignjatović, S., Rakicević, L., Novković, M., Kusić-Tisma, J., Radojković, D., Strugarević, E., Čalija, B., Radak, Đ.,& Kovac, M.. (2016). Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study. in Current Vascular Pharmacology
Bentham Science Publ Ltd, Sharjah., 14(6), 563-569.
https://doi.org/10.2174/1570161114666160714103148

Backović D, Ignjatović S, Rakicević L, Novković M, Kusić-Tisma J, Radojković D, Strugarević E, Čalija B, Radak Đ, Kovac M. Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study. in Current Vascular Pharmacology. 2016;14(6):563-569.
doi:10.2174/1570161114666160714103148 .

Backović, Dragana, Ignjatović, Svetlana, Rakicević, Ljiljana, Novković, Mirjana, Kusić-Tisma, Jelena, Radojković, Dragica, Strugarević, Evgenija, Čalija, Branko, Radak, Đorđe, Kovac, Mirjana, "Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study" in Current Vascular Pharmacology, 14, no. 6 (2016):563-569,
https://doi.org/10.2174/1570161114666160714103148 . .

TY  - CONF
AU  - Backović, D.
AU  - Ignjatović, Svetlana
AU  - Rakicević, Ljiljana
AU  - Novković, Mirjana
AU  - Kusić-Tisma, Jelena
AU  - Radojković, Dragica
AU  - Strugarević, Evgenija
AU  - Čalija, Branko
AU  - Radak, Đorđe
AU  - Kovac, M.
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2744
AB  - Background: Carotid endarterectomy (CEA) is the standard treatment
for carotid stenosis. Dual antiplatelet therapy, including aspirin and
clopidogrel, has a potential role in reducing the risk of stroke after car-
otid surgery. However, clopidogrel high on-treatment platelet reactiv-
ity (HTPR) is quite a common phenomenon.
Aims: Our study aimed to evaluate genetic and non-genetic factors as
possible risks for clopidogrel-HTPR in patients with carotid artery
stenosis undergoing CEA.
Methods: Using multiple-electrode impedance aggregometry (MEA)
the antiplatelet effectiveness of clopidogrel was prospectively evaluated
in 112 patients (66.2   8.1 years). Measurements were made after 24 h,
7 and 30 days of clopidogrel treatment, which was introduced after
elective CEA at a dose of 75 mg daily, for at least 30 days. Clopido-
grel-HTPR was defined as an adenosine diphosphate (ADP) - throm-
bin receptor activating peptide (TRAP) platelet aggregation ratio ≥
52%. CYP2C19*2 genotyping was performed by TaqMan assay.
Logistic regression models were used to estimate predictors for low
responsiveness. The Ethics Committee of the “Dedinje” Institute for
Cardiovascular Diseases approved the research protocol. All patients
gave written informed consent prior to study inclusion.
Results: According to this specific cut-off value for our population, the
number of patients with HTPR declined from 79.5% 24 h after intro-
ducing clopidogrel to 25% after 30 days of treatment. Analysis showed
that 16/30 patients carrying the CYP2C19*2 gene variant had HTPR,
in contrast to 12/82 non-carriers of this allele (P< 0.001). Multivariate
logistic regression analysis identified the CYP2C19*2 gene variant
(OR 4.384, 95% CI 1.296-14.833, P=0.017) and high total cholesterol
(OR 2.090, 95% CI 1.263-3.459, P=0.004) as the only independent risk
factors for clopidogrel-HTPR.
Conclusions: The CYP2C19*2 gene variant and high total cholesterol
level were risk factors for clopidogrel-HTPR in patients with carotid
artery stenosis undergoing CEA.
PB  - Elsevier
C3  - Journal of Thrombosis and Haemostasis
T1  - Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy
VL  - 14
IS  - S1
SP  - 110
EP  - 110
DO  - 10.1111/jth.13325
ER  - 

@conference{
author = "Backović, D. and Ignjatović, Svetlana and Rakicević, Ljiljana and Novković, Mirjana and Kusić-Tisma, Jelena and Radojković, Dragica and Strugarević, Evgenija and Čalija, Branko and Radak, Đorđe and Kovac, M.",
year = "2016",
abstract = "Background: Carotid endarterectomy (CEA) is the standard treatment
for carotid stenosis. Dual antiplatelet therapy, including aspirin and
clopidogrel, has a potential role in reducing the risk of stroke after car-
otid surgery. However, clopidogrel high on-treatment platelet reactiv-
ity (HTPR) is quite a common phenomenon.
Aims: Our study aimed to evaluate genetic and non-genetic factors as
possible risks for clopidogrel-HTPR in patients with carotid artery
stenosis undergoing CEA.
Methods: Using multiple-electrode impedance aggregometry (MEA)
the antiplatelet effectiveness of clopidogrel was prospectively evaluated
in 112 patients (66.2   8.1 years). Measurements were made after 24 h,
7 and 30 days of clopidogrel treatment, which was introduced after
elective CEA at a dose of 75 mg daily, for at least 30 days. Clopido-
grel-HTPR was defined as an adenosine diphosphate (ADP) - throm-
bin receptor activating peptide (TRAP) platelet aggregation ratio ≥
52%. CYP2C19*2 genotyping was performed by TaqMan assay.
Logistic regression models were used to estimate predictors for low
responsiveness. The Ethics Committee of the “Dedinje” Institute for
Cardiovascular Diseases approved the research protocol. All patients
gave written informed consent prior to study inclusion.
Results: According to this specific cut-off value for our population, the
number of patients with HTPR declined from 79.5% 24 h after intro-
ducing clopidogrel to 25% after 30 days of treatment. Analysis showed
that 16/30 patients carrying the CYP2C19*2 gene variant had HTPR,
in contrast to 12/82 non-carriers of this allele (P< 0.001). Multivariate
logistic regression analysis identified the CYP2C19*2 gene variant
(OR 4.384, 95% CI 1.296-14.833, P=0.017) and high total cholesterol
(OR 2.090, 95% CI 1.263-3.459, P=0.004) as the only independent risk
factors for clopidogrel-HTPR.
Conclusions: The CYP2C19*2 gene variant and high total cholesterol
level were risk factors for clopidogrel-HTPR in patients with carotid
artery stenosis undergoing CEA.",
publisher = "Elsevier",
journal = "Journal of Thrombosis and Haemostasis",
title = "Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy",
volume = "14",
number = "S1",
pages = "110-110",
doi = "10.1111/jth.13325"
}

Backović, D., Ignjatović, S., Rakicević, L., Novković, M., Kusić-Tisma, J., Radojković, D., Strugarević, E., Čalija, B., Radak, Đ.,& Kovac, M.. (2016). Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy. in Journal of Thrombosis and Haemostasis
Elsevier., 14(S1), 110-110.
https://doi.org/10.1111/jth.13325

Backović D, Ignjatović S, Rakicević L, Novković M, Kusić-Tisma J, Radojković D, Strugarević E, Čalija B, Radak Đ, Kovac M. Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy. in Journal of Thrombosis and Haemostasis. 2016;14(S1):110-110.
doi:10.1111/jth.13325 .

Backović, D., Ignjatović, Svetlana, Rakicević, Ljiljana, Novković, Mirjana, Kusić-Tisma, Jelena, Radojković, Dragica, Strugarević, Evgenija, Čalija, Branko, Radak, Đorđe, Kovac, M., "Risk factors for clopidogrel high on-treatment platelet reactivity in patients with carotid artery stenosis undergoing endarterectomy" in Journal of Thrombosis and Haemostasis, 14, no. S1 (2016):110-110,
https://doi.org/10.1111/jth.13325 . .

TY  - JOUR
AU  - Ljujić, Mila
AU  - Mijatović, Sanja
AU  - Bulatović, Mirna Z.
AU  - Mojic, Marija
AU  - Maksimović-Ivanić, Danijela
AU  - Radojković, Dragica
AU  - Topić, Aleksandra
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2773
AB  - Alpha-1-antitrypsin (AAT), an acute phase protein, is the principal circulatory anti-protease. This multifunctional protein is encoded by the SERPINA1 gene. Although AAT was recognised as a potential tumour marker, its role in cancer biology remains unknown. Given that it has been demonstrated that AAT has an anti-apoptotic property against non-malignant cells, we aimed to investigate whether AAT affects apoptosis in a colon cancer cell line (HCT116). The presence of AAT in the HCT116 cell culture antagonized cytotoxicity of blockers of MEK1/2, PI3K/Akt pathways as well as NF-kappa B. The dominantly recovered cell viability was observed in the co-treatment with MEK1/2 inhibitor U0126. In addition, it was revealed that AAT almost completely abolished U0126-induced apoptosis through maintenance of the autophagy process. Our study revealed for the first time that the observed cyto-protection triggered by AAT was accompanied by sustained autophagy which opposed apoptosis. These results may contribute to understanding of the role of AAT in cancer development and evaluation of efficacy of cancer therapy.
PB  - Maik Nauka/Interperiodica/Springer, New York
T2  - Molecular Biology
T1  - ALPHA-1 Antitrypsin Affects U0126-Induced Cytotoxicity in Colon Cancer Cell Line (HCT116)
VL  - 50
IS  - 1
SP  - 153
EP  - 156
DO  - 10.1134/S002689331601012X
ER  - 

@article{
author = "Ljujić, Mila and Mijatović, Sanja and Bulatović, Mirna Z. and Mojic, Marija and Maksimović-Ivanić, Danijela and Radojković, Dragica and Topić, Aleksandra",
year = "2016",
abstract = "Alpha-1-antitrypsin (AAT), an acute phase protein, is the principal circulatory anti-protease. This multifunctional protein is encoded by the SERPINA1 gene. Although AAT was recognised as a potential tumour marker, its role in cancer biology remains unknown. Given that it has been demonstrated that AAT has an anti-apoptotic property against non-malignant cells, we aimed to investigate whether AAT affects apoptosis in a colon cancer cell line (HCT116). The presence of AAT in the HCT116 cell culture antagonized cytotoxicity of blockers of MEK1/2, PI3K/Akt pathways as well as NF-kappa B. The dominantly recovered cell viability was observed in the co-treatment with MEK1/2 inhibitor U0126. In addition, it was revealed that AAT almost completely abolished U0126-induced apoptosis through maintenance of the autophagy process. Our study revealed for the first time that the observed cyto-protection triggered by AAT was accompanied by sustained autophagy which opposed apoptosis. These results may contribute to understanding of the role of AAT in cancer development and evaluation of efficacy of cancer therapy.",
publisher = "Maik Nauka/Interperiodica/Springer, New York",
journal = "Molecular Biology",
title = "ALPHA-1 Antitrypsin Affects U0126-Induced Cytotoxicity in Colon Cancer Cell Line (HCT116)",
volume = "50",
number = "1",
pages = "153-156",
doi = "10.1134/S002689331601012X"
}

Ljujić, M., Mijatović, S., Bulatović, M. Z., Mojic, M., Maksimović-Ivanić, D., Radojković, D.,& Topić, A.. (2016). ALPHA-1 Antitrypsin Affects U0126-Induced Cytotoxicity in Colon Cancer Cell Line (HCT116). in Molecular Biology
Maik Nauka/Interperiodica/Springer, New York., 50(1), 153-156.
https://doi.org/10.1134/S002689331601012X

Ljujić M, Mijatović S, Bulatović MZ, Mojic M, Maksimović-Ivanić D, Radojković D, Topić A. ALPHA-1 Antitrypsin Affects U0126-Induced Cytotoxicity in Colon Cancer Cell Line (HCT116). in Molecular Biology. 2016;50(1):153-156.
doi:10.1134/S002689331601012X .

Ljujić, Mila, Mijatović, Sanja, Bulatović, Mirna Z., Mojic, Marija, Maksimović-Ivanić, Danijela, Radojković, Dragica, Topić, Aleksandra, "ALPHA-1 Antitrypsin Affects U0126-Induced Cytotoxicity in Colon Cancer Cell Line (HCT116)" in Molecular Biology, 50, no. 1 (2016):153-156,
https://doi.org/10.1134/S002689331601012X . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Nagorni-Obradović, Ljudmila
AU  - Francuski, Đorđe
AU  - Ljujić, Mila
AU  - Malić, Živka
AU  - Radojković, Dragica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2771
AB  - Alpha-1-antitrypsin deficiency (AATD) and tobacco smoke play a key role in the pathogenesis of early-onset emphysema. Differences in AATD-related chronic obstructive pulmonary disease stages imply the existence of modifying factors associated with disease severity. We present two male patients with emphysema caused by severe AATD (PiZZ genotype). Both are former smokers and have epoxide hydrolase low-activity phenotype. Extremely high level of oxidative stress (high urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine), increased inflammation (high serum CRP), and GSTP1 105Val mutation were found in patient with a worse lung function and prognosis. These data provide more evidence that oxidative stress-related gene variants and inflammation are associated with worse symptoms of AATD-related emphysema. Therefore, prevention against severe stage of AATD-related emphysema would include early identification of the risk gene variants, cessation or never smoking, and treatment with anti-inflammatory and anti-oxidant drugs. Additionally, urinary 8-oxodG could be a candidate for predictive biomarker for routine assessment of the oxidative stress level in AATD patients.
PB  - Springer/Plenum Publishers, New York
T2  - Biochemical Genetics
T1  - Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency
VL  - 54
IS  - 5
SP  - 746
EP  - 752
DO  - 10.1007/s10528-016-9748-7
ER  - 

@article{
author = "Topić, Aleksandra and Nagorni-Obradović, Ljudmila and Francuski, Đorđe and Ljujić, Mila and Malić, Živka and Radojković, Dragica",
year = "2016",
abstract = "Alpha-1-antitrypsin deficiency (AATD) and tobacco smoke play a key role in the pathogenesis of early-onset emphysema. Differences in AATD-related chronic obstructive pulmonary disease stages imply the existence of modifying factors associated with disease severity. We present two male patients with emphysema caused by severe AATD (PiZZ genotype). Both are former smokers and have epoxide hydrolase low-activity phenotype. Extremely high level of oxidative stress (high urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine), increased inflammation (high serum CRP), and GSTP1 105Val mutation were found in patient with a worse lung function and prognosis. These data provide more evidence that oxidative stress-related gene variants and inflammation are associated with worse symptoms of AATD-related emphysema. Therefore, prevention against severe stage of AATD-related emphysema would include early identification of the risk gene variants, cessation or never smoking, and treatment with anti-inflammatory and anti-oxidant drugs. Additionally, urinary 8-oxodG could be a candidate for predictive biomarker for routine assessment of the oxidative stress level in AATD patients.",
publisher = "Springer/Plenum Publishers, New York",
journal = "Biochemical Genetics",
title = "Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency",
volume = "54",
number = "5",
pages = "746-752",
doi = "10.1007/s10528-016-9748-7"
}

Topić, A., Nagorni-Obradović, L., Francuski, Đ., Ljujić, M., Malić, Ž.,& Radojković, D.. (2016). Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency. in Biochemical Genetics
Springer/Plenum Publishers, New York., 54(5), 746-752.
https://doi.org/10.1007/s10528-016-9748-7

Topić A, Nagorni-Obradović L, Francuski Đ, Ljujić M, Malić Ž, Radojković D. Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency. in Biochemical Genetics. 2016;54(5):746-752.
doi:10.1007/s10528-016-9748-7 .

Topić, Aleksandra, Nagorni-Obradović, Ljudmila, Francuski, Đorđe, Ljujić, Mila, Malić, Živka, Radojković, Dragica, "Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency" in Biochemical Genetics, 54, no. 5 (2016):746-752,
https://doi.org/10.1007/s10528-016-9748-7 . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Malić, Živka
AU  - Francuski, Đorđe
AU  - Stanković, Marija
AU  - Marković, Bojan
AU  - Soskić, Blagoje
AU  - Tomić, Branko
AU  - Ilić, Stefan
AU  - Dobrivojević, Snežana
AU  - Drca, Sanja
AU  - Radojković, Dragica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2600
AB  - Gender-related differences in the association between polymorphism of xenobiotic-metabolising enzymes or non-genetic biomarkers and susceptibility to oxidative stress was assessed in healthy middle-aged Serbian adults, by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG/creatinine) and total antioxidant status in serum (TAOS). Females were more susceptible to oxidative stress. In both genders, positive predictor of the antioxidative protection was serum triglyceride, while BMI  lt 25 kg/m(2) was associated with oxidative stress. Susceptibility to oxidative stress in males was associated with GSTT1*null allele and increased serum iron, but in females, it was decreased serum bilirubin. Early identification of the risk factors could be important in the prevention of oxidative stress-related diseases.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Biomarkers
T1  - Gender-related differences in susceptibility to oxidative stress in healthy middle-aged Serbian adults
VL  - 21
IS  - 2
SP  - 186
EP  - 193
DO  - 10.3109/1354750X.2015.1126647
ER  - 

@article{
author = "Topić, Aleksandra and Malić, Živka and Francuski, Đorđe and Stanković, Marija and Marković, Bojan and Soskić, Blagoje and Tomić, Branko and Ilić, Stefan and Dobrivojević, Snežana and Drca, Sanja and Radojković, Dragica",
year = "2016",
abstract = "Gender-related differences in the association between polymorphism of xenobiotic-metabolising enzymes or non-genetic biomarkers and susceptibility to oxidative stress was assessed in healthy middle-aged Serbian adults, by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG/creatinine) and total antioxidant status in serum (TAOS). Females were more susceptible to oxidative stress. In both genders, positive predictor of the antioxidative protection was serum triglyceride, while BMI  lt 25 kg/m(2) was associated with oxidative stress. Susceptibility to oxidative stress in males was associated with GSTT1*null allele and increased serum iron, but in females, it was decreased serum bilirubin. Early identification of the risk factors could be important in the prevention of oxidative stress-related diseases.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Biomarkers",
title = "Gender-related differences in susceptibility to oxidative stress in healthy middle-aged Serbian adults",
volume = "21",
number = "2",
pages = "186-193",
doi = "10.3109/1354750X.2015.1126647"
}

Topić, A., Malić, Ž., Francuski, Đ., Stanković, M., Marković, B., Soskić, B., Tomić, B., Ilić, S., Dobrivojević, S., Drca, S.,& Radojković, D.. (2016). Gender-related differences in susceptibility to oxidative stress in healthy middle-aged Serbian adults. in Biomarkers
Taylor & Francis Ltd, Abingdon., 21(2), 186-193.
https://doi.org/10.3109/1354750X.2015.1126647

Topić A, Malić Ž, Francuski Đ, Stanković M, Marković B, Soskić B, Tomić B, Ilić S, Dobrivojević S, Drca S, Radojković D. Gender-related differences in susceptibility to oxidative stress in healthy middle-aged Serbian adults. in Biomarkers. 2016;21(2):186-193.
doi:10.3109/1354750X.2015.1126647 .

Topić, Aleksandra, Malić, Živka, Francuski, Đorđe, Stanković, Marija, Marković, Bojan, Soskić, Blagoje, Tomić, Branko, Ilić, Stefan, Dobrivojević, Snežana, Drca, Sanja, Radojković, Dragica, "Gender-related differences in susceptibility to oxidative stress in healthy middle-aged Serbian adults" in Biomarkers, 21, no. 2 (2016):186-193,
https://doi.org/10.3109/1354750X.2015.1126647 . .

TY  - JOUR
AU  - Backović, Dragana
AU  - Ignjatović, Svetlana
AU  - Rakicević, Ljiljana
AU  - Kusić-Tisma, Jelena
AU  - Radojković, Dragica
AU  - Čalija, Branko
AU  - Strugarević, Evgenija
AU  - Radak, Đorđe
AU  - Kovac, Mirjana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2573
AB  - Background: Despite the proven clinical effect of oral antiplatelet drugs, a considerable number of patients do not have an adequate response to clopidogrel. The aim of our study was to determine the influence of CYP2C19*2 loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis. Methods: One hundred and twelve patients with carotid artery stenosis undergoing endarterectomy were included in this one-year prospective study. All of them received clopidogrel (75 mg daily) for at least 30 days after the intervention. They were followed from the moment of hospital admission. CYP2C19*2 genotyping was performed by TaqMan Assay. The influence of CYP2C19*2 variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA). Results: Genotyping results showed that 82 (73.2%) patients were homozygous for wild type, 29 (25.9%) were heterozygous for the CYP2C19*2 allele and 1 (0.9%) was CYP2C19*2 homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the CYP2C19*2 alleles 10%. In the wild type group, 74.4% were clopidogrel responders after 7 days of taking the drug; 82.9% after 30 days of clopidogrel introduction, respectively. In patients with the CYP2C19*2 alleles the number of responders increased up to 46.7% after 7 days; 53.3% after 30 days of taking the drug, respectively. The risk for being a low-responder is higher for the patients heterozygous for the CYP2C19*2 allele vs. wild type (OR 4.250, 95% CI 1.695-10.658, P lt 0.01). Conclusions: The CYP2C19*2 loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Influence of Cyp2c19∗2 Gene Variant on Therapeutic Response during Clopidogrel Treatment in Patients with Carotid Artery Stenosis
VL  - 35
IS  - 1
SP  - 26
EP  - 33
DO  - 10.1515/jomb-2015-0009
ER  - 

@article{
author = "Backović, Dragana and Ignjatović, Svetlana and Rakicević, Ljiljana and Kusić-Tisma, Jelena and Radojković, Dragica and Čalija, Branko and Strugarević, Evgenija and Radak, Đorđe and Kovac, Mirjana",
year = "2016",
abstract = "Background: Despite the proven clinical effect of oral antiplatelet drugs, a considerable number of patients do not have an adequate response to clopidogrel. The aim of our study was to determine the influence of CYP2C19*2 loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis. Methods: One hundred and twelve patients with carotid artery stenosis undergoing endarterectomy were included in this one-year prospective study. All of them received clopidogrel (75 mg daily) for at least 30 days after the intervention. They were followed from the moment of hospital admission. CYP2C19*2 genotyping was performed by TaqMan Assay. The influence of CYP2C19*2 variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA). Results: Genotyping results showed that 82 (73.2%) patients were homozygous for wild type, 29 (25.9%) were heterozygous for the CYP2C19*2 allele and 1 (0.9%) was CYP2C19*2 homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the CYP2C19*2 alleles 10%. In the wild type group, 74.4% were clopidogrel responders after 7 days of taking the drug; 82.9% after 30 days of clopidogrel introduction, respectively. In patients with the CYP2C19*2 alleles the number of responders increased up to 46.7% after 7 days; 53.3% after 30 days of taking the drug, respectively. The risk for being a low-responder is higher for the patients heterozygous for the CYP2C19*2 allele vs. wild type (OR 4.250, 95% CI 1.695-10.658, P lt 0.01). Conclusions: The CYP2C19*2 loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Influence of Cyp2c19∗2 Gene Variant on Therapeutic Response during Clopidogrel Treatment in Patients with Carotid Artery Stenosis",
volume = "35",
number = "1",
pages = "26-33",
doi = "10.1515/jomb-2015-0009"
}

Backović, D., Ignjatović, S., Rakicević, L., Kusić-Tisma, J., Radojković, D., Čalija, B., Strugarević, E., Radak, Đ.,& Kovac, M.. (2016). Influence of Cyp2c19∗2 Gene Variant on Therapeutic Response during Clopidogrel Treatment in Patients with Carotid Artery Stenosis. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 35(1), 26-33.
https://doi.org/10.1515/jomb-2015-0009

Backović D, Ignjatović S, Rakicević L, Kusić-Tisma J, Radojković D, Čalija B, Strugarević E, Radak Đ, Kovac M. Influence of Cyp2c19∗2 Gene Variant on Therapeutic Response during Clopidogrel Treatment in Patients with Carotid Artery Stenosis. in Journal of Medical Biochemistry. 2016;35(1):26-33.
doi:10.1515/jomb-2015-0009 .

Backović, Dragana, Ignjatović, Svetlana, Rakicević, Ljiljana, Kusić-Tisma, Jelena, Radojković, Dragica, Čalija, Branko, Strugarević, Evgenija, Radak, Đorđe, Kovac, Mirjana, "Influence of Cyp2c19∗2 Gene Variant on Therapeutic Response during Clopidogrel Treatment in Patients with Carotid Artery Stenosis" in Journal of Medical Biochemistry, 35, no. 1 (2016):26-33,
https://doi.org/10.1515/jomb-2015-0009 . .

TY  - JOUR
AU  - Beletić, Anđelo
AU  - Dudvarski-Ilić, Aleksandra
AU  - Milenković, Branislava
AU  - Nagorni-Obradović, Ljudmila
AU  - Ljujić, Mila
AU  - Đorđević, Valentina
AU  - Mirković, Duško
AU  - Radojković, Dragica
AU  - Majkić-Singh, Nada
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2204
AB  - Introduction: Alpha-1-antitrypsin deficiency (AATD), genetic risk factor for premature chronic obstructive pulmonary disease (COPD), often remains undetected. The aim of our study was to analyse the effectiveness of an integrative laboratory algorithm for AATD detection in patients diagnosed with COPD by the age of 45 years, in comparison with the screening approach based on AAT concentration measurement alone. Subjects and methods: 50 unrelated patients (28 males / 22 females, age 52 (24-75 years) diagnosed with COPD before the age of 45 years were enrolled. Immunonephelometric assay for alpha-1-antitrypsin (AAT) and PCR-reverse hybridization for Z and S allele were first-line, and isoelectric focusing and DNA sequencing (ABI Prism BigDye) were reflex tests. Results: AATD associated genotypes were detected in 7 patients (5 ZZ, 1 ZM(malton), 1 ZQ0(amersfoort)), 10 were heterozygous carriers (8 MZ and 2 MS genotypes) and 33 were without AATD (MM genotype). Carriers and patients without AATD had comparable AAT concentrations (P = 0.125). In majority of participants (48) first line tests were sufficient to analyze AATD presence. In two remaining cases reflex tests identified rare alleles, M-malton and Q0(amersfoort), the later one being reported for the first time in Serbian population. Detection rate did not differ between algorithm and screening both for AATD (P = 0.500) and carriers (P = 0.063). Conclusion: There is a high prevalence of AATD affected subjects and carriers in a group of patients with premature COPD. The use of integrative laboratory algorithm does not improve the effectiveness of AATD detection in comparison with the screening based on AAT concentration alone.
PB  - Croatian Soc Medical Biochemists, Zagreb
T2  - Biochemia Medica
T1  - Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?
VL  - 24
IS  - 2
SP  - 293
EP  - 298
DO  - 10.11613/BM.2014.032
ER  - 

@article{
author = "Beletić, Anđelo and Dudvarski-Ilić, Aleksandra and Milenković, Branislava and Nagorni-Obradović, Ljudmila and Ljujić, Mila and Đorđević, Valentina and Mirković, Duško and Radojković, Dragica and Majkić-Singh, Nada",
year = "2014",
abstract = "Introduction: Alpha-1-antitrypsin deficiency (AATD), genetic risk factor for premature chronic obstructive pulmonary disease (COPD), often remains undetected. The aim of our study was to analyse the effectiveness of an integrative laboratory algorithm for AATD detection in patients diagnosed with COPD by the age of 45 years, in comparison with the screening approach based on AAT concentration measurement alone. Subjects and methods: 50 unrelated patients (28 males / 22 females, age 52 (24-75 years) diagnosed with COPD before the age of 45 years were enrolled. Immunonephelometric assay for alpha-1-antitrypsin (AAT) and PCR-reverse hybridization for Z and S allele were first-line, and isoelectric focusing and DNA sequencing (ABI Prism BigDye) were reflex tests. Results: AATD associated genotypes were detected in 7 patients (5 ZZ, 1 ZM(malton), 1 ZQ0(amersfoort)), 10 were heterozygous carriers (8 MZ and 2 MS genotypes) and 33 were without AATD (MM genotype). Carriers and patients without AATD had comparable AAT concentrations (P = 0.125). In majority of participants (48) first line tests were sufficient to analyze AATD presence. In two remaining cases reflex tests identified rare alleles, M-malton and Q0(amersfoort), the later one being reported for the first time in Serbian population. Detection rate did not differ between algorithm and screening both for AATD (P = 0.500) and carriers (P = 0.063). Conclusion: There is a high prevalence of AATD affected subjects and carriers in a group of patients with premature COPD. The use of integrative laboratory algorithm does not improve the effectiveness of AATD detection in comparison with the screening based on AAT concentration alone.",
publisher = "Croatian Soc Medical Biochemists, Zagreb",
journal = "Biochemia Medica",
title = "Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?",
volume = "24",
number = "2",
pages = "293-298",
doi = "10.11613/BM.2014.032"
}

Beletić, A., Dudvarski-Ilić, A., Milenković, B., Nagorni-Obradović, L., Ljujić, M., Đorđević, V., Mirković, D., Radojković, D.,& Majkić-Singh, N.. (2014). Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?. in Biochemia Medica
Croatian Soc Medical Biochemists, Zagreb., 24(2), 293-298.
https://doi.org/10.11613/BM.2014.032

Beletić A, Dudvarski-Ilić A, Milenković B, Nagorni-Obradović L, Ljujić M, Đorđević V, Mirković D, Radojković D, Majkić-Singh N. Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?. in Biochemia Medica. 2014;24(2):293-298.
doi:10.11613/BM.2014.032 .

Beletić, Anđelo, Dudvarski-Ilić, Aleksandra, Milenković, Branislava, Nagorni-Obradović, Ljudmila, Ljujić, Mila, Đorđević, Valentina, Mirković, Duško, Radojković, Dragica, Majkić-Singh, Nada, "Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?" in Biochemia Medica, 24, no. 2 (2014):293-298,
https://doi.org/10.11613/BM.2014.032 . .

TY  - JOUR
AU  - Petrović-Stanojević, Nataša
AU  - Topić, Aleksandra
AU  - Nikolić, Aleksandra
AU  - Stankovic, Marija
AU  - Dopuđa-Pantić, Vesna
AU  - Milenković, Branislava
AU  - Radojković, Dragica
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2142
AB  - Background and Objectives Polymorphisms of beta2-adrenergic receptor gene (ADRB2) are clinically relevant for several reasons, including as a risk factor for asthma development/severity and predicting the effectiveness of treatment with beta2-agonists in reducing asthma symptoms. The aim of this study was to examine the association between ADRB2 gene polymorphisms and asthma in the Serbian population, and to evaluate the therapeutic response in relation to the ADRB2 genotype. Methods The study included 171 patients with asthma and 101 healthy subjects as the control group. Genotyping of Arg16Gly and Gln27Glu polymorphisms was performed by direct sequencing of polymerase chain reaction (PCR) products. Results In Serbian adults, carriers of the 27Gln allele and 27Gln/Gln genotype were at higher risk of asthma [odds ratio (OR) 2.5, 95 % confidence interval (CI) 1.6-3.8, and OR 3.00, 95 % CI 1.7-5.3, respectively], while the presence of the 27Glu allele and 27Gln/Glu genotype were found to be protective of asthma (OR 0.4, 95 % CI 0.3-0.6, and OR 0.3, 95 % CI 0.1-0.7, respectively). Furthermore, we found that the presence of the 27Gln allele in asthmatics younger than 50 years leads to a better response to therapy with long-acting beta2-agonists (LABA) in combination with prevailing low and moderate doses of inhaled corticosteroids (ICS), while carriers of the 27Glu allele over 50 years old are more likely to respond to LABA + ICS therapy. Conclusion We identified that in Serbian adults the 27Gln allele and 27Gln homozygosity are risk factors for asthma, which may be of clinical interest in disease prevention. The finding that younger carriers of the 27Gln allele respond better to LABA + ICS therapy may be utilized in personalized asthma treatment.
PB  - Adis Int Ltd, Northcote
T2  - Molecular Diagnosis & Therapy
T1  - Polymorphisms of Beta2-Adrenergic Receptor Gene in Serbian Asthmatic Adults: Effects on Response to Beta-Agonists
VL  - 18
IS  - 6
SP  - 639
EP  - 646
DO  - 10.1007/s40291-014-0116-1
ER  - 

@article{
author = "Petrović-Stanojević, Nataša and Topić, Aleksandra and Nikolić, Aleksandra and Stankovic, Marija and Dopuđa-Pantić, Vesna and Milenković, Branislava and Radojković, Dragica",
year = "2014",
abstract = "Background and Objectives Polymorphisms of beta2-adrenergic receptor gene (ADRB2) are clinically relevant for several reasons, including as a risk factor for asthma development/severity and predicting the effectiveness of treatment with beta2-agonists in reducing asthma symptoms. The aim of this study was to examine the association between ADRB2 gene polymorphisms and asthma in the Serbian population, and to evaluate the therapeutic response in relation to the ADRB2 genotype. Methods The study included 171 patients with asthma and 101 healthy subjects as the control group. Genotyping of Arg16Gly and Gln27Glu polymorphisms was performed by direct sequencing of polymerase chain reaction (PCR) products. Results In Serbian adults, carriers of the 27Gln allele and 27Gln/Gln genotype were at higher risk of asthma [odds ratio (OR) 2.5, 95 % confidence interval (CI) 1.6-3.8, and OR 3.00, 95 % CI 1.7-5.3, respectively], while the presence of the 27Glu allele and 27Gln/Glu genotype were found to be protective of asthma (OR 0.4, 95 % CI 0.3-0.6, and OR 0.3, 95 % CI 0.1-0.7, respectively). Furthermore, we found that the presence of the 27Gln allele in asthmatics younger than 50 years leads to a better response to therapy with long-acting beta2-agonists (LABA) in combination with prevailing low and moderate doses of inhaled corticosteroids (ICS), while carriers of the 27Glu allele over 50 years old are more likely to respond to LABA + ICS therapy. Conclusion We identified that in Serbian adults the 27Gln allele and 27Gln homozygosity are risk factors for asthma, which may be of clinical interest in disease prevention. The finding that younger carriers of the 27Gln allele respond better to LABA + ICS therapy may be utilized in personalized asthma treatment.",
publisher = "Adis Int Ltd, Northcote",
journal = "Molecular Diagnosis & Therapy",
title = "Polymorphisms of Beta2-Adrenergic Receptor Gene in Serbian Asthmatic Adults: Effects on Response to Beta-Agonists",
volume = "18",
number = "6",
pages = "639-646",
doi = "10.1007/s40291-014-0116-1"
}

Petrović-Stanojević, N., Topić, A., Nikolić, A., Stankovic, M., Dopuđa-Pantić, V., Milenković, B.,& Radojković, D.. (2014). Polymorphisms of Beta2-Adrenergic Receptor Gene in Serbian Asthmatic Adults: Effects on Response to Beta-Agonists. in Molecular Diagnosis & Therapy
Adis Int Ltd, Northcote., 18(6), 639-646.
https://doi.org/10.1007/s40291-014-0116-1

Petrović-Stanojević N, Topić A, Nikolić A, Stankovic M, Dopuđa-Pantić V, Milenković B, Radojković D. Polymorphisms of Beta2-Adrenergic Receptor Gene in Serbian Asthmatic Adults: Effects on Response to Beta-Agonists. in Molecular Diagnosis & Therapy. 2014;18(6):639-646.
doi:10.1007/s40291-014-0116-1 .

Petrović-Stanojević, Nataša, Topić, Aleksandra, Nikolić, Aleksandra, Stankovic, Marija, Dopuđa-Pantić, Vesna, Milenković, Branislava, Radojković, Dragica, "Polymorphisms of Beta2-Adrenergic Receptor Gene in Serbian Asthmatic Adults: Effects on Response to Beta-Agonists" in Molecular Diagnosis & Therapy, 18, no. 6 (2014):639-646,
https://doi.org/10.1007/s40291-014-0116-1 . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Francuski, Đorđe
AU  - Marković, Bojan
AU  - Stanković, Marija
AU  - Dobrivojević, Snežana
AU  - Drca, Sanja
AU  - Radojković, Dragica
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1917
AB  - Objectives: Although there are many nucleobase modifications, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is one of the dominant form of oxidative modifications of DNA. Urinary 8-oxodG is potentially the best non-invasive biomarker of oxidative stress. Defining reference interval for urinary 8-oxodG is a prerequisite for its clinical use as biomarker. Design and methods: Reference population included 229 healthy Serbian adults (130 males and 99 females). The spot urinary 8-oxodG was determined using high performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). Urinary creatinine was measured by the kinetic Jaffe method. Results: Analytical performances of the HPLC-MS/MS: CVs within and between-run variations were 5.6% and 2.6%; LOD and LOQ were 1.65 nmol/L and 330 nmol/L; mean recovery and relative accuracy were 96% and 97%. Creatinine level was higher in males than in females, but no gender difference in 8-oxodG level was observed. Upon the adjustment of 8-oxodG to creatinine (8-oxodG/creatinine), higher values were obtained in females (1.38 +/- 0.65 nmol/mmol) than in males (1.05 +/- 0.48 nmol/mmol). Distribution of 8-oxodG/creatinine in spot urine sample was log-normal and gender-related reference intervals (estimated as the 2.5th-97.5th percentiles) were 0.45-2.22 nmol/mmol for males, and 0.54-3.11 nmol/mmol for females. Body mass index (BMI) affects excretion of the 8-oxodG in males, independently of urinary creatinine, while in females it does not. Therefore, BMI might contribute to the gender-related differences of 8-oxodG/creatinine in spot urine samples. Conclusions: This is the first established gender-related reference intervals of spot urinary 8-oxodG/creatinine. Our results contribute to the full validation of 8-oxodG as biomarker of oxidative stress.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Clinical Biochemistry
T1  - Gender-related reference intervals of urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine determined by liquid chromatography-tandem mass spectrometry in Serbian population
VL  - 46
IS  - 4-5
SP  - 321
EP  - 326
DO  - 10.1016/j.clinbiochem.2012.12.008
ER  - 

@article{
author = "Topić, Aleksandra and Francuski, Đorđe and Marković, Bojan and Stanković, Marija and Dobrivojević, Snežana and Drca, Sanja and Radojković, Dragica",
year = "2013",
abstract = "Objectives: Although there are many nucleobase modifications, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is one of the dominant form of oxidative modifications of DNA. Urinary 8-oxodG is potentially the best non-invasive biomarker of oxidative stress. Defining reference interval for urinary 8-oxodG is a prerequisite for its clinical use as biomarker. Design and methods: Reference population included 229 healthy Serbian adults (130 males and 99 females). The spot urinary 8-oxodG was determined using high performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). Urinary creatinine was measured by the kinetic Jaffe method. Results: Analytical performances of the HPLC-MS/MS: CVs within and between-run variations were 5.6% and 2.6%; LOD and LOQ were 1.65 nmol/L and 330 nmol/L; mean recovery and relative accuracy were 96% and 97%. Creatinine level was higher in males than in females, but no gender difference in 8-oxodG level was observed. Upon the adjustment of 8-oxodG to creatinine (8-oxodG/creatinine), higher values were obtained in females (1.38 +/- 0.65 nmol/mmol) than in males (1.05 +/- 0.48 nmol/mmol). Distribution of 8-oxodG/creatinine in spot urine sample was log-normal and gender-related reference intervals (estimated as the 2.5th-97.5th percentiles) were 0.45-2.22 nmol/mmol for males, and 0.54-3.11 nmol/mmol for females. Body mass index (BMI) affects excretion of the 8-oxodG in males, independently of urinary creatinine, while in females it does not. Therefore, BMI might contribute to the gender-related differences of 8-oxodG/creatinine in spot urine samples. Conclusions: This is the first established gender-related reference intervals of spot urinary 8-oxodG/creatinine. Our results contribute to the full validation of 8-oxodG as biomarker of oxidative stress.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Clinical Biochemistry",
title = "Gender-related reference intervals of urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine determined by liquid chromatography-tandem mass spectrometry in Serbian population",
volume = "46",
number = "4-5",
pages = "321-326",
doi = "10.1016/j.clinbiochem.2012.12.008"
}

Topić, A., Francuski, Đ., Marković, B., Stanković, M., Dobrivojević, S., Drca, S.,& Radojković, D.. (2013). Gender-related reference intervals of urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine determined by liquid chromatography-tandem mass spectrometry in Serbian population. in Clinical Biochemistry
Pergamon-Elsevier Science Ltd, Oxford., 46(4-5), 321-326.
https://doi.org/10.1016/j.clinbiochem.2012.12.008

Topić A, Francuski Đ, Marković B, Stanković M, Dobrivojević S, Drca S, Radojković D. Gender-related reference intervals of urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine determined by liquid chromatography-tandem mass spectrometry in Serbian population. in Clinical Biochemistry. 2013;46(4-5):321-326.
doi:10.1016/j.clinbiochem.2012.12.008 .

Topić, Aleksandra, Francuski, Đorđe, Marković, Bojan, Stanković, Marija, Dobrivojević, Snežana, Drca, Sanja, Radojković, Dragica, "Gender-related reference intervals of urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine determined by liquid chromatography-tandem mass spectrometry in Serbian population" in Clinical Biochemistry, 46, no. 4-5 (2013):321-326,
https://doi.org/10.1016/j.clinbiochem.2012.12.008 . .

TY  - CONF
AU  - Topić, Aleksandra
AU  - Francuski, Đorđe
AU  - Marković, Bojan
AU  - Stanković, M.
AU  - Dobrivojević, Snežana
AU  - Drca, Sanja
AU  - Radojković, Dragica
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1648
PB  - Wiley-Blackwell, Hoboken
C3  - FEBS Journal
T1  - Gender-related reference intervals for urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine adjusted to creatinine (8-oxodG/creatinine) determined with liquid chromatography-tandem mass spectrometry
VL  - 279
IS  - Supplement 1
SP  - 203
EP  - 203
DO  - 10.1111/j.1742-4658.2010.08705.x
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1648
ER  - 

@conference{
author = "Topić, Aleksandra and Francuski, Đorđe and Marković, Bojan and Stanković, M. and Dobrivojević, Snežana and Drca, Sanja and Radojković, Dragica",
year = "2012",
publisher = "Wiley-Blackwell, Hoboken",
journal = "FEBS Journal",
title = "Gender-related reference intervals for urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine adjusted to creatinine (8-oxodG/creatinine) determined with liquid chromatography-tandem mass spectrometry",
volume = "279",
number = "Supplement 1",
pages = "203-203",
doi = "10.1111/j.1742-4658.2010.08705.x",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1648"
}

Topić, A., Francuski, Đ., Marković, B., Stanković, M., Dobrivojević, S., Drca, S.,& Radojković, D.. (2012). Gender-related reference intervals for urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine adjusted to creatinine (8-oxodG/creatinine) determined with liquid chromatography-tandem mass spectrometry. in FEBS Journal
Wiley-Blackwell, Hoboken., 279(Supplement 1), 203-203.
https://doi.org/10.1111/j.1742-4658.2010.08705.x
https://hdl.handle.net/21.15107/rcub_farfar_1648

Topić A, Francuski Đ, Marković B, Stanković M, Dobrivojević S, Drca S, Radojković D. Gender-related reference intervals for urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine adjusted to creatinine (8-oxodG/creatinine) determined with liquid chromatography-tandem mass spectrometry. in FEBS Journal. 2012;279(Supplement 1):203-203.
doi:10.1111/j.1742-4658.2010.08705.x
https://hdl.handle.net/21.15107/rcub_farfar_1648 .

Topić, Aleksandra, Francuski, Đorđe, Marković, Bojan, Stanković, M., Dobrivojević, Snežana, Drca, Sanja, Radojković, Dragica, "Gender-related reference intervals for urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine adjusted to creatinine (8-oxodG/creatinine) determined with liquid chromatography-tandem mass spectrometry" in FEBS Journal, 279, no. Supplement 1 (2012):203-203,
https://doi.org/10.1111/j.1742-4658.2010.08705.x .,
https://hdl.handle.net/21.15107/rcub_farfar_1648 .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Stankovic, Marija
AU  - Divac-Rankov, Aleksandra
AU  - Petrović-Stanojević, Nataša
AU  - Mitić-Milikić, Marija
AU  - Nagorni-Obradović, Ljudmila
AU  - Radojković, Dragica
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1633
AB  - Aim: Alpha-1-antitrypsin (A1AT) is the main inhibitor of neutrophil elastase, and severe alpha-1-antitrypsin deficiency (A1ATD) is a genetic risk factor for early-onset emphysema. Despite the relatively high prevalence of A1ATD, this condition is frequently underdiagnosed. Our aim was to determine the distribution of the A1ATD phenotypes/alleles in patients with lung diseases as well as in the Serbian population. Methods: The study included the adults with chronic obstructive pulmonary disease (COPD) (n = 348), asthma (n = 71), and bronchiectasis (n = 35); the control was 1435 healthy blood donors. The A1ATD variants were identified by isoelectric focusing or polymerase chain reaction-mediated site-directed mutagenesis. Results: PiMZ heterozygotes, PiZZ homozygotes, and Z allele carriers are associated with significantly higher risk of developing COPD than healthy individuals (odds ratios 3.43, 42.42, and 5.49 respectively). The calculated prevalence of PiZZ, PiMZ, and PiSZ was higher in patients with COPD (1:202, 1:8, and 1:1243) than in the Serbian population (1: 5519, 1: 38, and 1:5519). Conclusion: The high prevalence of A1ATD phenotypes/allele in our population has confirmed the necessity of screening for A1ATD in patients with COPD. On the other hand, on the basis of the estimated number of those with A1ATD among the COPD patients, it is possible to assess the diagnostic efficiency of A1ATD in the Serbian population.
PB  - Mary Ann Liebert Inc, New Rochelle
T2  - Genetic Testing and Molecular Biomarkers
T1  - Alpha-1-Antitrypsin Deficiency in Serbian Adults with Lung Diseases
VL  - 16
IS  - 11
SP  - 1282
EP  - 1286
DO  - 10.1089/gtmb.2012.0152
ER  - 

@article{
author = "Topić, Aleksandra and Stankovic, Marija and Divac-Rankov, Aleksandra and Petrović-Stanojević, Nataša and Mitić-Milikić, Marija and Nagorni-Obradović, Ljudmila and Radojković, Dragica",
year = "2012",
abstract = "Aim: Alpha-1-antitrypsin (A1AT) is the main inhibitor of neutrophil elastase, and severe alpha-1-antitrypsin deficiency (A1ATD) is a genetic risk factor for early-onset emphysema. Despite the relatively high prevalence of A1ATD, this condition is frequently underdiagnosed. Our aim was to determine the distribution of the A1ATD phenotypes/alleles in patients with lung diseases as well as in the Serbian population. Methods: The study included the adults with chronic obstructive pulmonary disease (COPD) (n = 348), asthma (n = 71), and bronchiectasis (n = 35); the control was 1435 healthy blood donors. The A1ATD variants were identified by isoelectric focusing or polymerase chain reaction-mediated site-directed mutagenesis. Results: PiMZ heterozygotes, PiZZ homozygotes, and Z allele carriers are associated with significantly higher risk of developing COPD than healthy individuals (odds ratios 3.43, 42.42, and 5.49 respectively). The calculated prevalence of PiZZ, PiMZ, and PiSZ was higher in patients with COPD (1:202, 1:8, and 1:1243) than in the Serbian population (1: 5519, 1: 38, and 1:5519). Conclusion: The high prevalence of A1ATD phenotypes/allele in our population has confirmed the necessity of screening for A1ATD in patients with COPD. On the other hand, on the basis of the estimated number of those with A1ATD among the COPD patients, it is possible to assess the diagnostic efficiency of A1ATD in the Serbian population.",
publisher = "Mary Ann Liebert Inc, New Rochelle",
journal = "Genetic Testing and Molecular Biomarkers",
title = "Alpha-1-Antitrypsin Deficiency in Serbian Adults with Lung Diseases",
volume = "16",
number = "11",
pages = "1282-1286",
doi = "10.1089/gtmb.2012.0152"
}

Topić, A., Stankovic, M., Divac-Rankov, A., Petrović-Stanojević, N., Mitić-Milikić, M., Nagorni-Obradović, L.,& Radojković, D.. (2012). Alpha-1-Antitrypsin Deficiency in Serbian Adults with Lung Diseases. in Genetic Testing and Molecular Biomarkers
Mary Ann Liebert Inc, New Rochelle., 16(11), 1282-1286.
https://doi.org/10.1089/gtmb.2012.0152

Topić A, Stankovic M, Divac-Rankov A, Petrović-Stanojević N, Mitić-Milikić M, Nagorni-Obradović L, Radojković D. Alpha-1-Antitrypsin Deficiency in Serbian Adults with Lung Diseases. in Genetic Testing and Molecular Biomarkers. 2012;16(11):1282-1286.
doi:10.1089/gtmb.2012.0152 .

Topić, Aleksandra, Stankovic, Marija, Divac-Rankov, Aleksandra, Petrović-Stanojević, Nataša, Mitić-Milikić, Marija, Nagorni-Obradović, Ljudmila, Radojković, Dragica, "Alpha-1-Antitrypsin Deficiency in Serbian Adults with Lung Diseases" in Genetic Testing and Molecular Biomarkers, 16, no. 11 (2012):1282-1286,
https://doi.org/10.1089/gtmb.2012.0152 . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Ljujić, Mila
AU  - Radojković, Dragica
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1659
AB  - Context: Alpha-1-antitrypsin (A1AT) is the most abundant liver-derived, highly polymorphic, glycoprotein in plasma. Hereditary deficiency of alpha-1-antitrypsin in plasma (A1ATD) is a consequence of accumulation of polymers of A1AT mutants in endoplasmic reticulum of hepatocytes and other A1AT-producing cells. One of the clinical manifestations of A1ATD is liver disease in childhood and cirrhosis and/or hepatocellular carcinoma (HCC) in adulthood. Epidemiology and pathophysiology of liver failure in early childhood caused by A1ATD are well known, but the association with hepatocellular carcinoma is not clarified. The aim of this article is to review different aspects of association between A1AT variants and hepatocellular carcinoma, with emphasis on the epidemiology and molecular pathogenesis. The significance of A1AT as a biomarker in the diagnosis of HCC is also discussed. Evidence Acquisitions: Search for relevant articles were performed through Pub Med, HighWire, and Science Direct using the keywords "alpha-1-antitrypsin", "liver diseases", "hepatocellular carcinoma", "SERPINA1". Articles published until 2011 were reviewed. Results: Epidemiology studies revealed that severe A1ATD is a significant risk factor for cirrhosis and HCC unrelated to the presence of HBV or HCV infections. However, predisposition to HCC in moderate A1ATD is rare, and probably happens in combination with HBV and/or HCV infections or other unknown risk factors. It is assumed that accumulation of polymers of A1ATD variants in endoplasmic reticulum of hepatocytes leads to damage of hepatocytes by gain-of-function mechanism. Also, increased level of A1AT was recognized as diagnostic and prognostic marker of HCC. Conclusions: Clarification of a carcinogenic role for A1ATD and identification of pro-inflammatory or some still unknown factors that lead to increased susceptibility to HCC associated with A1ATD may contribute to a better understanding of hepatic carcinogenesis and to the development of new drugs.
PB  - Kowsar Publ, Hoensbroek
T2  - Hepatitis Monthly
T1  - Alpha-1-Antitrypsin in Pathogenesis of Hepatocellular Carcinoma
VL  - 12
IS  - 10
DO  - 10.5812/hepatmon.7042
ER  - 

@article{
author = "Topić, Aleksandra and Ljujić, Mila and Radojković, Dragica",
year = "2012",
abstract = "Context: Alpha-1-antitrypsin (A1AT) is the most abundant liver-derived, highly polymorphic, glycoprotein in plasma. Hereditary deficiency of alpha-1-antitrypsin in plasma (A1ATD) is a consequence of accumulation of polymers of A1AT mutants in endoplasmic reticulum of hepatocytes and other A1AT-producing cells. One of the clinical manifestations of A1ATD is liver disease in childhood and cirrhosis and/or hepatocellular carcinoma (HCC) in adulthood. Epidemiology and pathophysiology of liver failure in early childhood caused by A1ATD are well known, but the association with hepatocellular carcinoma is not clarified. The aim of this article is to review different aspects of association between A1AT variants and hepatocellular carcinoma, with emphasis on the epidemiology and molecular pathogenesis. The significance of A1AT as a biomarker in the diagnosis of HCC is also discussed. Evidence Acquisitions: Search for relevant articles were performed through Pub Med, HighWire, and Science Direct using the keywords "alpha-1-antitrypsin", "liver diseases", "hepatocellular carcinoma", "SERPINA1". Articles published until 2011 were reviewed. Results: Epidemiology studies revealed that severe A1ATD is a significant risk factor for cirrhosis and HCC unrelated to the presence of HBV or HCV infections. However, predisposition to HCC in moderate A1ATD is rare, and probably happens in combination with HBV and/or HCV infections or other unknown risk factors. It is assumed that accumulation of polymers of A1ATD variants in endoplasmic reticulum of hepatocytes leads to damage of hepatocytes by gain-of-function mechanism. Also, increased level of A1AT was recognized as diagnostic and prognostic marker of HCC. Conclusions: Clarification of a carcinogenic role for A1ATD and identification of pro-inflammatory or some still unknown factors that lead to increased susceptibility to HCC associated with A1ATD may contribute to a better understanding of hepatic carcinogenesis and to the development of new drugs.",
publisher = "Kowsar Publ, Hoensbroek",
journal = "Hepatitis Monthly",
title = "Alpha-1-Antitrypsin in Pathogenesis of Hepatocellular Carcinoma",
volume = "12",
number = "10",
doi = "10.5812/hepatmon.7042"
}

Topić, A., Ljujić, M.,& Radojković, D.. (2012). Alpha-1-Antitrypsin in Pathogenesis of Hepatocellular Carcinoma. in Hepatitis Monthly
Kowsar Publ, Hoensbroek., 12(10).
https://doi.org/10.5812/hepatmon.7042

Topić A, Ljujić M, Radojković D. Alpha-1-Antitrypsin in Pathogenesis of Hepatocellular Carcinoma. in Hepatitis Monthly. 2012;12(10).
doi:10.5812/hepatmon.7042 .

Topić, Aleksandra, Ljujić, Mila, Radojković, Dragica, "Alpha-1-Antitrypsin in Pathogenesis of Hepatocellular Carcinoma" in Hepatitis Monthly, 12, no. 10 (2012),
https://doi.org/10.5812/hepatmon.7042 . .

TY  - CONF
AU  - Beletić, Anđelo
AU  - Đorđević, Valentina
AU  - Canić, I.
AU  - Kocica, T.
AU  - Kuzmanović, I.
AU  - Golubović, Milka
AU  - Mirković, Duško
AU  - Radojković, Dragica
AU  - Majkić-Singh, Nada
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1531
PB  - Walter de Gruyter & Co, Berlin
C3  - Clinical Chemistry and Laboratory Medicine
T1  - Experiences in simultaneous detection of factor v leiden, factor ii g20210a, mthfr c677t and mthfr a1298c mutations in patients with thrombophilia
VL  - 49
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1531
ER  - 

@conference{
author = "Beletić, Anđelo and Đorđević, Valentina and Canić, I. and Kocica, T. and Kuzmanović, I. and Golubović, Milka and Mirković, Duško and Radojković, Dragica and Majkić-Singh, Nada",
year = "2011",
publisher = "Walter de Gruyter & Co, Berlin",
journal = "Clinical Chemistry and Laboratory Medicine",
title = "Experiences in simultaneous detection of factor v leiden, factor ii g20210a, mthfr c677t and mthfr a1298c mutations in patients with thrombophilia",
volume = "49",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1531"
}

Beletić, A., Đorđević, V., Canić, I., Kocica, T., Kuzmanović, I., Golubović, M., Mirković, D., Radojković, D.,& Majkić-Singh, N.. (2011). Experiences in simultaneous detection of factor v leiden, factor ii g20210a, mthfr c677t and mthfr a1298c mutations in patients with thrombophilia. in Clinical Chemistry and Laboratory Medicine
Walter de Gruyter & Co, Berlin., 49.
https://hdl.handle.net/21.15107/rcub_farfar_1531

Beletić A, Đorđević V, Canić I, Kocica T, Kuzmanović I, Golubović M, Mirković D, Radojković D, Majkić-Singh N. Experiences in simultaneous detection of factor v leiden, factor ii g20210a, mthfr c677t and mthfr a1298c mutations in patients with thrombophilia. in Clinical Chemistry and Laboratory Medicine. 2011;49.
https://hdl.handle.net/21.15107/rcub_farfar_1531 .

Beletić, Anđelo, Đorđević, Valentina, Canić, I., Kocica, T., Kuzmanović, I., Golubović, Milka, Mirković, Duško, Radojković, Dragica, Majkić-Singh, Nada, "Experiences in simultaneous detection of factor v leiden, factor ii g20210a, mthfr c677t and mthfr a1298c mutations in patients with thrombophilia" in Clinical Chemistry and Laboratory Medicine, 49 (2011),
https://hdl.handle.net/21.15107/rcub_farfar_1531 .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Ljujić, Mila
AU  - Nikolić, Aleksandra
AU  - Petrović-Stanojević, Nataša
AU  - Dopuđa-Pantić, Vesna
AU  - Mitić-Milikić, Marija
AU  - Radojković, Dragica
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1547
AB  - Imbalance between neutrophil elastase and alpha-1-antitrypsin (AAT) leads to emphysema in smokers as well as in patients with inherited alpha-1-antitrypsin deficiency. AAT as a proven inhibitor of apoptosis may play role in lung cancer (LC) progression. The aim was to analyse AAT protein variants and polymorphism in promoter region of the neutrophil elastase gene (ELA2) in patients with primary lung cancer. AAT phenotypisation by isoelectric focusing method and ELA2 gene promoter characterization by DNA sequencing were performed in 66 patients with primary lung cancer. Results showed that the frequency of M1 allele and PiM1 homozygotes in LC patients was significantly higher when compared to the healthy subjects (f = 0.6360 and 0.7424 respectively). The most frequent ELA2 promoter region genotypes in LC patients were -903TT and -741GG. There were significantly more patients with intermediate and high ELA2 genotype activity, compared to those with low activity (91% vs. 9%, respectively). In conclusion, we found that PiM1 homozygosity could be associated with the lung cancer, probably due to increased synthesis of this antiapoptotic protein. Non-MM variants of AAT and ELA2 genotypes with predicted intermediate or high activity could also represent a risk factor for aggressive form of lung cancer associated with extrathoracic metastases.
PB  - Springer, Dordrecht
T2  - Pathology & Oncology Research
T1  - Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer
VL  - 17
IS  - 1
SP  - 75
EP  - 80
DO  - 10.1007/s12253-010-9283-5
ER  - 

@article{
author = "Topić, Aleksandra and Ljujić, Mila and Nikolić, Aleksandra and Petrović-Stanojević, Nataša and Dopuđa-Pantić, Vesna and Mitić-Milikić, Marija and Radojković, Dragica",
year = "2011",
abstract = "Imbalance between neutrophil elastase and alpha-1-antitrypsin (AAT) leads to emphysema in smokers as well as in patients with inherited alpha-1-antitrypsin deficiency. AAT as a proven inhibitor of apoptosis may play role in lung cancer (LC) progression. The aim was to analyse AAT protein variants and polymorphism in promoter region of the neutrophil elastase gene (ELA2) in patients with primary lung cancer. AAT phenotypisation by isoelectric focusing method and ELA2 gene promoter characterization by DNA sequencing were performed in 66 patients with primary lung cancer. Results showed that the frequency of M1 allele and PiM1 homozygotes in LC patients was significantly higher when compared to the healthy subjects (f = 0.6360 and 0.7424 respectively). The most frequent ELA2 promoter region genotypes in LC patients were -903TT and -741GG. There were significantly more patients with intermediate and high ELA2 genotype activity, compared to those with low activity (91% vs. 9%, respectively). In conclusion, we found that PiM1 homozygosity could be associated with the lung cancer, probably due to increased synthesis of this antiapoptotic protein. Non-MM variants of AAT and ELA2 genotypes with predicted intermediate or high activity could also represent a risk factor for aggressive form of lung cancer associated with extrathoracic metastases.",
publisher = "Springer, Dordrecht",
journal = "Pathology & Oncology Research",
title = "Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer",
volume = "17",
number = "1",
pages = "75-80",
doi = "10.1007/s12253-010-9283-5"
}

Topić, A., Ljujić, M., Nikolić, A., Petrović-Stanojević, N., Dopuđa-Pantić, V., Mitić-Milikić, M.,& Radojković, D.. (2011). Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer. in Pathology & Oncology Research
Springer, Dordrecht., 17(1), 75-80.
https://doi.org/10.1007/s12253-010-9283-5

Topić A, Ljujić M, Nikolić A, Petrović-Stanojević N, Dopuđa-Pantić V, Mitić-Milikić M, Radojković D. Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer. in Pathology & Oncology Research. 2011;17(1):75-80.
doi:10.1007/s12253-010-9283-5 .

Topić, Aleksandra, Ljujić, Mila, Nikolić, Aleksandra, Petrović-Stanojević, Nataša, Dopuđa-Pantić, Vesna, Mitić-Milikić, Marija, Radojković, Dragica, "Alpha-1-antitrypsin Phenotypes and Neutrophil Elastase Gene Promoter Polymorphisms in Lung Cancer" in Pathology & Oncology Research, 17, no. 1 (2011):75-80,
https://doi.org/10.1007/s12253-010-9283-5 . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Ljujić, Mila
AU  - Petrović-Stanojević, Nataša
AU  - Dopuđa-Pantić, Vesna
AU  - Radojković, Dragica
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1508
AB  - Propose: Alpha-1-antitrypsin (AAT) as the major circulating inhibitor of proteases has important role in protease-antiprotease homeostasis. Recent studies have confirmed its antiapoptotic role. AAT is a highly polymorphic protein. Individuals with normal variants have normal serum levels and functional activity of ATT. However, individuals with hereditary AAT deficiency (AATD) have low circulating levels of AAT. Severe AATD was identified as genetic risk factor for early onset of pulmonary emphysema. Association between AAT phenotypes and lung cancer (LC) is not clear; and different studies show contradictory results. The aim of this case-control study was to investigate phenotypes and serum level of AAT in LC. Methods: The study group included 147 patients with LC, classified as small cell lung cancer (SCLC, n=42) and non-small cell lung cancer (NSCLC, n=105). The control group consisted of 273 healthy blood donors. AAT phenotyping was performed by isoelectric-focusing and AAT concentration was measured using nephelometry. Results: There were no differences in the frequencies of AAT phenotypes and alleles between the control group and LC patients, as well as between NSCLC and SCLC groups. An elevated level of AAT was obtained in LC patients. PiMZ and PiMS phenotypes in LC patients were not deficient in the classical sense. AAT levels were 90 and 134%, respectively, when compared to PiMM phenotype in the control group. Conclusion: Our findings revealed that moderate deficiency of AAT is not risk factor for LC development. Although polymorphism of AAT was not associated with risk of LC, further research of this antiprotease and antiapoptotic protein could clarify its role in carcinogenesis, given its high concentration in LC patients, even in AATD patients.
PB  - Balkan Union of Oncology (B.U.ON.)
T2  - Journal of BUON
T1  - Phenotypes and serum level of alpha-1-antitrypsin in lung cancer
VL  - 16
IS  - 4
SP  - 672
EP  - 676
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1508
ER  - 

@article{
author = "Topić, Aleksandra and Ljujić, Mila and Petrović-Stanojević, Nataša and Dopuđa-Pantić, Vesna and Radojković, Dragica",
year = "2011",
abstract = "Propose: Alpha-1-antitrypsin (AAT) as the major circulating inhibitor of proteases has important role in protease-antiprotease homeostasis. Recent studies have confirmed its antiapoptotic role. AAT is a highly polymorphic protein. Individuals with normal variants have normal serum levels and functional activity of ATT. However, individuals with hereditary AAT deficiency (AATD) have low circulating levels of AAT. Severe AATD was identified as genetic risk factor for early onset of pulmonary emphysema. Association between AAT phenotypes and lung cancer (LC) is not clear; and different studies show contradictory results. The aim of this case-control study was to investigate phenotypes and serum level of AAT in LC. Methods: The study group included 147 patients with LC, classified as small cell lung cancer (SCLC, n=42) and non-small cell lung cancer (NSCLC, n=105). The control group consisted of 273 healthy blood donors. AAT phenotyping was performed by isoelectric-focusing and AAT concentration was measured using nephelometry. Results: There were no differences in the frequencies of AAT phenotypes and alleles between the control group and LC patients, as well as between NSCLC and SCLC groups. An elevated level of AAT was obtained in LC patients. PiMZ and PiMS phenotypes in LC patients were not deficient in the classical sense. AAT levels were 90 and 134%, respectively, when compared to PiMM phenotype in the control group. Conclusion: Our findings revealed that moderate deficiency of AAT is not risk factor for LC development. Although polymorphism of AAT was not associated with risk of LC, further research of this antiprotease and antiapoptotic protein could clarify its role in carcinogenesis, given its high concentration in LC patients, even in AATD patients.",
publisher = "Balkan Union of Oncology (B.U.ON.)",
journal = "Journal of BUON",
title = "Phenotypes and serum level of alpha-1-antitrypsin in lung cancer",
volume = "16",
number = "4",
pages = "672-676",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1508"
}

Topić, A., Ljujić, M., Petrović-Stanojević, N., Dopuđa-Pantić, V.,& Radojković, D.. (2011). Phenotypes and serum level of alpha-1-antitrypsin in lung cancer. in Journal of BUON
Balkan Union of Oncology (B.U.ON.)., 16(4), 672-676.
https://hdl.handle.net/21.15107/rcub_farfar_1508

Topić A, Ljujić M, Petrović-Stanojević N, Dopuđa-Pantić V, Radojković D. Phenotypes and serum level of alpha-1-antitrypsin in lung cancer. in Journal of BUON. 2011;16(4):672-676.
https://hdl.handle.net/21.15107/rcub_farfar_1508 .

Topić, Aleksandra, Ljujić, Mila, Petrović-Stanojević, Nataša, Dopuđa-Pantić, Vesna, Radojković, Dragica, "Phenotypes and serum level of alpha-1-antitrypsin in lung cancer" in Journal of BUON, 16, no. 4 (2011):672-676,
https://hdl.handle.net/21.15107/rcub_farfar_1508 .

TY  - JOUR
AU  - Ljujić, Mila
AU  - Topić, Aleksandra
AU  - Nikolić, Aleksandra
AU  - Divac, Aleksandra
AU  - Grujić, Milan
AU  - Mitić-Milikić, Marija
AU  - Radojković, Dragica
PY  - 2010
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1383
AB  - The alpha-1-antitrypsin (A1AT) gene is highly polymorphic, with more than 100 genetic variants identified of which some can affect A1AT protein concentration and/or function and lead to pulmonary and/or liver disease. This study reports on the characterization of a p.G320R variant found in two patients, one with emphysema and the other with lung cancer. This variant results from a single base-pair substitution in exon 4 of the A1AT gene, and has been characterized as P by isoelectric focusing. Functional evaluation of the A1AT p.G320R variant was through comparing specific trypsin inhibitory activity in two patients with pulmonary disorders, carriers of the p.G320R variant, and 19 healthy individuals, carriers of normal A1AT M variants. Results showed that specific trypsin inhibitory activity was lower in both emphysema (2.45 mU/g) and lung cancer (2.07 mU/g) patients than in carriers of the normal variants (range 2.51-3.71 mU/g). This rare A1AT variant is associated with reduced functional activity of A1AT protein. Considering that it was found in patients with severe pulmonary disorders, this variant could be of clinical significance.
PB  - Soc Brasil Genetica, Ribeirao Pret
T2  - Genetics and Molecular Biology
T1  - Identification of a rare p.G320R alpha-1-antitrypsin variant in emphysema and lung cancer patients
VL  - 33
IS  - 1
SP  - 5
EP  - 8
DO  - 10.1590/S1415-47572009005000100
ER  - 

@article{
author = "Ljujić, Mila and Topić, Aleksandra and Nikolić, Aleksandra and Divac, Aleksandra and Grujić, Milan and Mitić-Milikić, Marija and Radojković, Dragica",
year = "2010",
abstract = "The alpha-1-antitrypsin (A1AT) gene is highly polymorphic, with more than 100 genetic variants identified of which some can affect A1AT protein concentration and/or function and lead to pulmonary and/or liver disease. This study reports on the characterization of a p.G320R variant found in two patients, one with emphysema and the other with lung cancer. This variant results from a single base-pair substitution in exon 4 of the A1AT gene, and has been characterized as P by isoelectric focusing. Functional evaluation of the A1AT p.G320R variant was through comparing specific trypsin inhibitory activity in two patients with pulmonary disorders, carriers of the p.G320R variant, and 19 healthy individuals, carriers of normal A1AT M variants. Results showed that specific trypsin inhibitory activity was lower in both emphysema (2.45 mU/g) and lung cancer (2.07 mU/g) patients than in carriers of the normal variants (range 2.51-3.71 mU/g). This rare A1AT variant is associated with reduced functional activity of A1AT protein. Considering that it was found in patients with severe pulmonary disorders, this variant could be of clinical significance.",
publisher = "Soc Brasil Genetica, Ribeirao Pret",
journal = "Genetics and Molecular Biology",
title = "Identification of a rare p.G320R alpha-1-antitrypsin variant in emphysema and lung cancer patients",
volume = "33",
number = "1",
pages = "5-8",
doi = "10.1590/S1415-47572009005000100"
}

Ljujić, M., Topić, A., Nikolić, A., Divac, A., Grujić, M., Mitić-Milikić, M.,& Radojković, D.. (2010). Identification of a rare p.G320R alpha-1-antitrypsin variant in emphysema and lung cancer patients. in Genetics and Molecular Biology
Soc Brasil Genetica, Ribeirao Pret., 33(1), 5-8.
https://doi.org/10.1590/S1415-47572009005000100

Ljujić M, Topić A, Nikolić A, Divac A, Grujić M, Mitić-Milikić M, Radojković D. Identification of a rare p.G320R alpha-1-antitrypsin variant in emphysema and lung cancer patients. in Genetics and Molecular Biology. 2010;33(1):5-8.
doi:10.1590/S1415-47572009005000100 .

Ljujić, Mila, Topić, Aleksandra, Nikolić, Aleksandra, Divac, Aleksandra, Grujić, Milan, Mitić-Milikić, Marija, Radojković, Dragica, "Identification of a rare p.G320R alpha-1-antitrypsin variant in emphysema and lung cancer patients" in Genetics and Molecular Biology, 33, no. 1 (2010):5-8,
https://doi.org/10.1590/S1415-47572009005000100 . .

TY  - JOUR
AU  - Beletić, Anđelo
AU  - Đorđević, Valentina
AU  - Dudvarski-Ilić, Aleksandra
AU  - Obradović, Ivana
AU  - Mirković, Duško
AU  - Ilić, Mirka
AU  - Radojković, Dragica
AU  - Majkić-Singh, Nada
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1163
AB  - Alpha-1-antitrypsin deficiency is a potentially lethal genetic disorder, which has pulmonary and liver manifestations. The standardized biochemical and molecular diagnostic protocol for detection of clinically relevant alleles is needed. The paper summarizes current concepts about AATD, describes the potentials of isoelectric focusing and PCR amplification-reverse allele specific oligonucleotide hybridization assay in the detection of affected individuals and shortly presents our experiences in the evaluation of AATD. We conclude that the systematic clinical laboratory approach to AATD might be based on the combination of mentioned methods, coordinated by alpha-1-antritrypsin quantification. Additionally, its complete medical implementation is achieved through teamwork between clinical chemists, molecular biologists and clinicians.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Isoelectrofocusing and PCR Amplification-Reverse Hybridization Assay in Evaluation of Alpha-1-Antitrypsin Deficiency
VL  - 28
IS  - 4
SP  - 241
EP  - 247
DO  - 10.2478/v10011-009-0023-x
ER  - 

@article{
author = "Beletić, Anđelo and Đorđević, Valentina and Dudvarski-Ilić, Aleksandra and Obradović, Ivana and Mirković, Duško and Ilić, Mirka and Radojković, Dragica and Majkić-Singh, Nada",
year = "2009",
abstract = "Alpha-1-antitrypsin deficiency is a potentially lethal genetic disorder, which has pulmonary and liver manifestations. The standardized biochemical and molecular diagnostic protocol for detection of clinically relevant alleles is needed. The paper summarizes current concepts about AATD, describes the potentials of isoelectric focusing and PCR amplification-reverse allele specific oligonucleotide hybridization assay in the detection of affected individuals and shortly presents our experiences in the evaluation of AATD. We conclude that the systematic clinical laboratory approach to AATD might be based on the combination of mentioned methods, coordinated by alpha-1-antritrypsin quantification. Additionally, its complete medical implementation is achieved through teamwork between clinical chemists, molecular biologists and clinicians.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Isoelectrofocusing and PCR Amplification-Reverse Hybridization Assay in Evaluation of Alpha-1-Antitrypsin Deficiency",
volume = "28",
number = "4",
pages = "241-247",
doi = "10.2478/v10011-009-0023-x"
}

Beletić, A., Đorđević, V., Dudvarski-Ilić, A., Obradović, I., Mirković, D., Ilić, M., Radojković, D.,& Majkić-Singh, N.. (2009). Isoelectrofocusing and PCR Amplification-Reverse Hybridization Assay in Evaluation of Alpha-1-Antitrypsin Deficiency. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 28(4), 241-247.
https://doi.org/10.2478/v10011-009-0023-x

Beletić A, Đorđević V, Dudvarski-Ilić A, Obradović I, Mirković D, Ilić M, Radojković D, Majkić-Singh N. Isoelectrofocusing and PCR Amplification-Reverse Hybridization Assay in Evaluation of Alpha-1-Antitrypsin Deficiency. in Journal of Medical Biochemistry. 2009;28(4):241-247.
doi:10.2478/v10011-009-0023-x .

Beletić, Anđelo, Đorđević, Valentina, Dudvarski-Ilić, Aleksandra, Obradović, Ivana, Mirković, Duško, Ilić, Mirka, Radojković, Dragica, Majkić-Singh, Nada, "Isoelectrofocusing and PCR Amplification-Reverse Hybridization Assay in Evaluation of Alpha-1-Antitrypsin Deficiency" in Journal of Medical Biochemistry, 28, no. 4 (2009):241-247,
https://doi.org/10.2478/v10011-009-0023-x . .