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  - 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  - 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  - 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  - 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 . .