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  - 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  - 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 .