Đorđević, Valentina

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orcid::0000-0002-3554-2796
  • Đorđević, Valentina (116)
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Author's Bibliography

Genome sequence diversity of SARS-CoV-2 in Serbia: insights gained from a 3-year pandemic study

Novković, Mirjana; Banović Đeri, Bojana; RistivojeviĆ, Bojan; Knežević, Aleksandra; Janković, Marko; Tanasić, Vanja; Radojičić, Verica; Keckarević, Dusan; Vidanović, Dejan; Tešović, Bojana; Skakić, Anita; Tolinački, Maja; Morić, Ivana; Đorđević, Valentina

(Frontiers, 2024)

TY  - JOUR
AU  - Novković, Mirjana
AU  - Banović Đeri, Bojana
AU  - RistivojeviĆ, Bojan
AU  - Knežević, Aleksandra
AU  - Janković, Marko
AU  - Tanasić, Vanja
AU  - Radojičić, Verica
AU  - Keckarević, Dusan
AU  - Vidanović, Dejan
AU  - Tešović, Bojana
AU  - Skakić, Anita
AU  - Tolinački, Maja
AU  - Morić, Ivana
AU  - Đorđević, Valentina
PY  - 2024
UR  - https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1332276
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2327
AB  - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, has been evolving rapidly causing emergence of new variants and health uncertainties. Monitoring the evolution of the virus was of the utmost importance for public health interventions and the development of national and global mitigation strategies. Here, we report national data on the emergence of new variants, their distribution, and dynamics in a 3-year study conducted from March 2020 to the end of January 2023 in the Republic of Serbia. Nasopharyngeal and oropharyngeal swabs from 2,398 COVID-19-positive patients were collected and sequenced using three different next generation technologies: Oxford Nanopore, Ion Torrent, and DNBSeq. In the subset of 2,107 SARS-CoV-2 sequences which met the quality requirements, detection of mutations, assignment to SARS-CoV-2 lineages, and phylogenetic analysis were performed. During the 3-year period, we detected three variants of concern, namely, Alpha (5.6%), Delta (7.4%), and Omicron (70.3%) and one variant of interest—Omicron recombinant “Kraken” (XBB1.5) (<1%), whereas 16.8% of the samples belonged to other SARS-CoV-2 (sub)lineages. The detected SARS-CoV-2 (sub)lineages resulted in eight COVID-19 pandemic waves in Serbia, which correspond to the pandemic waves reported in Europe and the United States. Wave dynamics in Serbia showed the most resemblance with the profile of pandemic waves in southern Europe, consistent with the southeastern European location of Serbia. The samples were assigned to sixteen SARS-CoV-2 Nextstrain clades: 20A, 20B, 20C, 20D, 20E, 20G, 20I, 21J, 21K, 21L, 22A, 22B, 22C, 22D, 22E, and 22F and six different Omicron recombinants (XZ, XAZ, XAS, XBB, XBF, and XBK). The 10 most common mutations detected in the coding and untranslated regions of the SARS-CoV-2 genomes included four mutations affecting the spike protein (S:D614G, S:T478K, S:P681H, and S:S477N) and one mutation at each of the following positions: 5′-untranslated region (5’UTR:241); N protein (N:RG203KR); NSP3 protein (NSP3:F106F); NSP4 protein (NSP4:T492I); NSP6 protein (NSP6: S106/G107/F108 - triple deletion), and NSP12b protein (NSP12b:P314L). This national-level study is the most comprehensive in terms of sequencing and genomic surveillance of SARS-CoV-2 during the pandemic in Serbia, highlighting the importance of establishing and maintaining good national practice for monitoring SARS-CoV-2 and other viruses circulating worldwide.
AB  - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, has been evolving rapidly causing emergence of new variants and health uncertainties. Monitoring the evolution of the virus was of the utmost importance for public health interventions and the development of national and global mitigation strategies. Here, we report national data on the emergence of new variants, their distribution, and dynamics in a 3-year study conducted from March 2020 to the end of January 2023 in the Republic of Serbia. Nasopharyngeal and oropharyngeal swabs from 2,398 COVID-19- positive patients were collected and sequenced using three different next generation technologies: Oxford Nanopore, Ion Torrent, and DNBSeq. In the subset of 2,107 SARS-CoV-2 sequences which met the quality requirements, detection of mutations, assignment to SARS-CoV-2 lineages, and phylogenetic analysis were performed. During the 3-year period, we detected three variants of concern, namely, Alpha (5.6%), Delta (7.4%), and Omicron (70.3%) and one variant of interest—Omicron recombinant “Kraken” (XBB1.5) (<1%), whereas 16.8% of the samples belonged to other SARS-CoV-2 (sub)lineages. The detected SARS-CoV-2 (sub)lineages resulted in eight COVID-19 pandemic waves in Serbia, which correspond to the pandemic waves reported in Europe and the United States. Wave dynamics in Serbia showed the most resemblance with the profile of pandemic waves in southern Europe, consistent with the southeastern European location of Serbia. The samples were assigned to sixteen SARS-CoV-2 Nextstrain clades: 20A, 20B, 20C, 20D, 20E, 20G, 20I, 21J, 21K, 21L, 22A, 22B, 22C, 22D, 22E, and 22F and six different Omicron recombinants (XZ, XAZ, XAS, XBB, XBF, and XBK). The 10 most common mutations detected in the coding and untranslated regions of the SARS-CoV-2 genomes included four mutations affecting the spike protein (S:D614G, S:T478K, S:P681H, and S:S477N) and one mutation at each of the following positions: 5′-untranslated region (5’UTR:241); N protein (N:RG203KR); NSP3 protein (NSP3:F106F); NSP4 protein (NSP4:T492I); NSP6 protein (NSP6: S106/G107/F108 - triple deletion), and NSP12b protein (NSP12b:P314L). This national-level study is the most comprehensive in terms of sequencing and genomic surveillance of SARS-CoV-2 during the pandemic in Serbia, highlighting the importance of establishing and maintaining good national practice for monitoring SARS-CoV-2 and other viruses circulating worldwide.
PB  - Frontiers
T2  - Frontiers in Microbiology
T2  - Frontiers in Microbiology
T1  - Genome sequence diversity of SARS-CoV-2 in Serbia: insights gained from a 3-year pandemic study
VL  - 15
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2327
ER  - 
@article{
author = "Novković, Mirjana and Banović Đeri, Bojana and RistivojeviĆ, Bojan and Knežević, Aleksandra and Janković, Marko and Tanasić, Vanja and Radojičić, Verica and Keckarević, Dusan and Vidanović, Dejan and Tešović, Bojana and Skakić, Anita and Tolinački, Maja and Morić, Ivana and Đorđević, Valentina",
year = "2024",
abstract = "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, has been evolving rapidly causing emergence of new variants and health uncertainties. Monitoring the evolution of the virus was of the utmost importance for public health interventions and the development of national and global mitigation strategies. Here, we report national data on the emergence of new variants, their distribution, and dynamics in a 3-year study conducted from March 2020 to the end of January 2023 in the Republic of Serbia. Nasopharyngeal and oropharyngeal swabs from 2,398 COVID-19-positive patients were collected and sequenced using three different next generation technologies: Oxford Nanopore, Ion Torrent, and DNBSeq. In the subset of 2,107 SARS-CoV-2 sequences which met the quality requirements, detection of mutations, assignment to SARS-CoV-2 lineages, and phylogenetic analysis were performed. During the 3-year period, we detected three variants of concern, namely, Alpha (5.6%), Delta (7.4%), and Omicron (70.3%) and one variant of interest—Omicron recombinant “Kraken” (XBB1.5) (<1%), whereas 16.8% of the samples belonged to other SARS-CoV-2 (sub)lineages. The detected SARS-CoV-2 (sub)lineages resulted in eight COVID-19 pandemic waves in Serbia, which correspond to the pandemic waves reported in Europe and the United States. Wave dynamics in Serbia showed the most resemblance with the profile of pandemic waves in southern Europe, consistent with the southeastern European location of Serbia. The samples were assigned to sixteen SARS-CoV-2 Nextstrain clades: 20A, 20B, 20C, 20D, 20E, 20G, 20I, 21J, 21K, 21L, 22A, 22B, 22C, 22D, 22E, and 22F and six different Omicron recombinants (XZ, XAZ, XAS, XBB, XBF, and XBK). The 10 most common mutations detected in the coding and untranslated regions of the SARS-CoV-2 genomes included four mutations affecting the spike protein (S:D614G, S:T478K, S:P681H, and S:S477N) and one mutation at each of the following positions: 5′-untranslated region (5’UTR:241); N protein (N:RG203KR); NSP3 protein (NSP3:F106F); NSP4 protein (NSP4:T492I); NSP6 protein (NSP6: S106/G107/F108 - triple deletion), and NSP12b protein (NSP12b:P314L). This national-level study is the most comprehensive in terms of sequencing and genomic surveillance of SARS-CoV-2 during the pandemic in Serbia, highlighting the importance of establishing and maintaining good national practice for monitoring SARS-CoV-2 and other viruses circulating worldwide., The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, has been evolving rapidly causing emergence of new variants and health uncertainties. Monitoring the evolution of the virus was of the utmost importance for public health interventions and the development of national and global mitigation strategies. Here, we report national data on the emergence of new variants, their distribution, and dynamics in a 3-year study conducted from March 2020 to the end of January 2023 in the Republic of Serbia. Nasopharyngeal and oropharyngeal swabs from 2,398 COVID-19- positive patients were collected and sequenced using three different next generation technologies: Oxford Nanopore, Ion Torrent, and DNBSeq. In the subset of 2,107 SARS-CoV-2 sequences which met the quality requirements, detection of mutations, assignment to SARS-CoV-2 lineages, and phylogenetic analysis were performed. During the 3-year period, we detected three variants of concern, namely, Alpha (5.6%), Delta (7.4%), and Omicron (70.3%) and one variant of interest—Omicron recombinant “Kraken” (XBB1.5) (<1%), whereas 16.8% of the samples belonged to other SARS-CoV-2 (sub)lineages. The detected SARS-CoV-2 (sub)lineages resulted in eight COVID-19 pandemic waves in Serbia, which correspond to the pandemic waves reported in Europe and the United States. Wave dynamics in Serbia showed the most resemblance with the profile of pandemic waves in southern Europe, consistent with the southeastern European location of Serbia. The samples were assigned to sixteen SARS-CoV-2 Nextstrain clades: 20A, 20B, 20C, 20D, 20E, 20G, 20I, 21J, 21K, 21L, 22A, 22B, 22C, 22D, 22E, and 22F and six different Omicron recombinants (XZ, XAZ, XAS, XBB, XBF, and XBK). The 10 most common mutations detected in the coding and untranslated regions of the SARS-CoV-2 genomes included four mutations affecting the spike protein (S:D614G, S:T478K, S:P681H, and S:S477N) and one mutation at each of the following positions: 5′-untranslated region (5’UTR:241); N protein (N:RG203KR); NSP3 protein (NSP3:F106F); NSP4 protein (NSP4:T492I); NSP6 protein (NSP6: S106/G107/F108 - triple deletion), and NSP12b protein (NSP12b:P314L). This national-level study is the most comprehensive in terms of sequencing and genomic surveillance of SARS-CoV-2 during the pandemic in Serbia, highlighting the importance of establishing and maintaining good national practice for monitoring SARS-CoV-2 and other viruses circulating worldwide.",
publisher = "Frontiers",
journal = "Frontiers in Microbiology, Frontiers in Microbiology",
title = "Genome sequence diversity of SARS-CoV-2 in Serbia: insights gained from a 3-year pandemic study",
volume = "15",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2327"
}
Novković, M., Banović Đeri, B., RistivojeviĆ, B., Knežević, A., Janković, M., Tanasić, V., Radojičić, V., Keckarević, D., Vidanović, D., Tešović, B., Skakić, A., Tolinački, M., Morić, I.,& Đorđević, V.. (2024). Genome sequence diversity of SARS-CoV-2 in Serbia: insights gained from a 3-year pandemic study. in Frontiers in Microbiology
Frontiers., 15.
https://hdl.handle.net/21.15107/rcub_imagine_2327
Novković M, Banović Đeri B, RistivojeviĆ B, Knežević A, Janković M, Tanasić V, Radojičić V, Keckarević D, Vidanović D, Tešović B, Skakić A, Tolinački M, Morić I, Đorđević V. Genome sequence diversity of SARS-CoV-2 in Serbia: insights gained from a 3-year pandemic study. in Frontiers in Microbiology. 2024;15.
https://hdl.handle.net/21.15107/rcub_imagine_2327 .
Novković, Mirjana, Banović Đeri, Bojana, RistivojeviĆ, Bojan, Knežević, Aleksandra, Janković, Marko, Tanasić, Vanja, Radojičić, Verica, Keckarević, Dusan, Vidanović, Dejan, Tešović, Bojana, Skakić, Anita, Tolinački, Maja, Morić, Ivana, Đorđević, Valentina, "Genome sequence diversity of SARS-CoV-2 in Serbia: insights gained from a 3-year pandemic study" in Frontiers in Microbiology, 15 (2024),
https://hdl.handle.net/21.15107/rcub_imagine_2327 .

The effect of prothrombin, the precursor of thrombin, on the proliferation and migration of colorectal cancer cells

Cumbo, Marija; Dunjić-Manevski, Sofija; Gvozdenov, Maja; Mitić, Martina Mia; Đorđević, Valentina; Tomić, Branko

(Serbian Biological Society, Institute for Biological Research "Siniša Stanković", 2024)

TY  - JOUR
AU  - Cumbo, Marija
AU  - Dunjić-Manevski, Sofija
AU  - Gvozdenov, Maja
AU  - Mitić, Martina Mia
AU  - Đorđević, Valentina
AU  - Tomić, Branko
PY  - 2024
UR  - https://doiserbia.nb.rs/Article.aspx?ID=0354-46642400007C
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2358
AB  - Thrombotic disorders are some of the main comorbidities in cancer patients. So far, research has indicated that thrombin, a key regulator of hemostasis, contributes to cancer progression. However, data on its origin in tumor microenvironments remain elusive. Based on previous research, we analyzed the RNA and protein expression of prothrombin, a precursor of thrombin, in selected colorectal cancer (CRC) cell lines. Since the effect of prothrombin in cancer development has not been previously reported, we treated the cells for 24 h and 48 h with different prothrombin concentrations and assessed the effect on cell proliferation and migration. Our results show that the tested CRC cell lines expressed prothrombin and that prothrombin inhibited proliferation and migration. The presented results suggest that prothrombin may contribute to CRC etiopathology and could serve as a potential diagnostic biomarker and therapeutic target. The mechanisms underlying prothrombin expression in cancer cells, potential prothrombin activation, and the underlying processes driving the described effects warrant further investigation.
PB  - Serbian Biological Society, Institute for Biological Research "Siniša Stanković"
T2  - Archives of Biological Sciences
T2  - Archives of Biological Sciences
T1  - The effect of prothrombin, the precursor of thrombin, on the proliferation and migration of colorectal cancer cells
EP  - 120
IS  - 1
SP  - 111
VL  - 76
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2358
ER  - 
@article{
author = "Cumbo, Marija and Dunjić-Manevski, Sofija and Gvozdenov, Maja and Mitić, Martina Mia and Đorđević, Valentina and Tomić, Branko",
year = "2024",
abstract = "Thrombotic disorders are some of the main comorbidities in cancer patients. So far, research has indicated that thrombin, a key regulator of hemostasis, contributes to cancer progression. However, data on its origin in tumor microenvironments remain elusive. Based on previous research, we analyzed the RNA and protein expression of prothrombin, a precursor of thrombin, in selected colorectal cancer (CRC) cell lines. Since the effect of prothrombin in cancer development has not been previously reported, we treated the cells for 24 h and 48 h with different prothrombin concentrations and assessed the effect on cell proliferation and migration. Our results show that the tested CRC cell lines expressed prothrombin and that prothrombin inhibited proliferation and migration. The presented results suggest that prothrombin may contribute to CRC etiopathology and could serve as a potential diagnostic biomarker and therapeutic target. The mechanisms underlying prothrombin expression in cancer cells, potential prothrombin activation, and the underlying processes driving the described effects warrant further investigation.",
publisher = "Serbian Biological Society, Institute for Biological Research "Siniša Stanković"",
journal = "Archives of Biological Sciences, Archives of Biological Sciences",
title = "The effect of prothrombin, the precursor of thrombin, on the proliferation and migration of colorectal cancer cells",
pages = "120-111",
number = "1",
volume = "76",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2358"
}
Cumbo, M., Dunjić-Manevski, S., Gvozdenov, M., Mitić, M. M., Đorđević, V.,& Tomić, B.. (2024). The effect of prothrombin, the precursor of thrombin, on the proliferation and migration of colorectal cancer cells. in Archives of Biological Sciences
Serbian Biological Society, Institute for Biological Research "Siniša Stanković"., 76(1), 111-120.
https://hdl.handle.net/21.15107/rcub_imagine_2358
Cumbo M, Dunjić-Manevski S, Gvozdenov M, Mitić MM, Đorđević V, Tomić B. The effect of prothrombin, the precursor of thrombin, on the proliferation and migration of colorectal cancer cells. in Archives of Biological Sciences. 2024;76(1):111-120.
https://hdl.handle.net/21.15107/rcub_imagine_2358 .
Cumbo, Marija, Dunjić-Manevski, Sofija, Gvozdenov, Maja, Mitić, Martina Mia, Đorđević, Valentina, Tomić, Branko, "The effect of prothrombin, the precursor of thrombin, on the proliferation and migration of colorectal cancer cells" in Archives of Biological Sciences, 76, no. 1 (2024):111-120,
https://hdl.handle.net/21.15107/rcub_imagine_2358 .

Using whole exome sequencing to explore genetic basis of unicuspid aortic valve disease

Mitić, Martina Mia; Ušjak, Dušan; Milošević, Maja; Cumbo, Marija; Dunjić Manevski, Sofija; Tomić, Branko; Petrović, Ivana; Otašević, Petar; Micović, Slobodan; Bojić, Milovan; Đorđević, Valentina

(Belgrade : Institute of molecular genetics and genetic engineering, 2023)

TY  - CONF
AU  - Mitić, Martina Mia
AU  - Ušjak, Dušan
AU  - Milošević, Maja
AU  - Cumbo, Marija
AU  - Dunjić Manevski, Sofija
AU  - Tomić, Branko
AU  - Petrović, Ivana
AU  - Otašević, Petar
AU  - Micović, Slobodan
AU  - Bojić, Milovan
AU  - Đorđević, Valentina
PY  - 2023
UR  - https://belbi.bg.ac.rs/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1999
AB  - Normal aortic valve consists of three cusps that develop in the embryonic stage. Unicuspid
aortic valve (UAV) is a rare congenital anomaly resulting in only one cusp with estimated
prevalence of 0.02% in general population. Aim of this study was to identify genetic
variants possibly associated with development of UAV. The study included 17 subjects,
namely 5 UAV patients and their healthy family members without UAV disorder. Total
DNA was isolated from venous blood samples and whole exomes sequencing (WES) was
performed using BGI’s WES protocol. Adapter-trimmed and quality-filtered reads (fastp)
were mapped to hg38 reference genome using BWA/SAMtools. VCF files were generated
using GATK (BaseRecalibrator, HaplotypeCaller) and annotated with InterVar and AnnoVar
tools. Rare heterozygous variants present in UAV patients were found in NOTCH1, TGFB2,
MYH6, EGFR, FBN2, C1R, ROBO4 and TBX5, genes associated with development of aortic
valves. Among these, most were missense mutations with damaging effects as predicted
using in silico tools (SIFT and/or Polyphen). Only mutation in MYH6 p.Ala1130Ser was
found in at least two different UAV patients. Also, rare homozygous missense mutation
p.Gly577Ser with high damaging potential was found in ADAMTS5 gene. Besides, highly
damaging heterozygous missense mutations were detected in gene interacting functional
partners (STRING) of genes associated with development of aortic valves: DVL1, THBS1,
NOTCH4, ADAMTS3, FBN1, NOTCH2, ADAM17, LRP5, WWTR1, C1S, ANKRD6 and TNNI1,
as well as homozygous in ACAN and KNG1. Taken together, malfunctions in ADAMTS5,
ACTA2, MYH6, FBN2, AXIN1, CELSR1 or TBX5 networks were found to be common in at
least two UAV patients, suggesting existence of genetic basis in UAV disorder, possibly as
a result of combined effects of multiple variants.
PB  - Belgrade : Institute of molecular genetics and genetic engineering
C3  - 4th Belgrade Bioinformatics Conference
T1  - Using whole exome sequencing to explore genetic basis of unicuspid aortic valve disease
EP  - 59
SP  - 59
VL  - 4
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1999
ER  - 
@conference{
author = "Mitić, Martina Mia and Ušjak, Dušan and Milošević, Maja and Cumbo, Marija and Dunjić Manevski, Sofija and Tomić, Branko and Petrović, Ivana and Otašević, Petar and Micović, Slobodan and Bojić, Milovan and Đorđević, Valentina",
year = "2023",
abstract = "Normal aortic valve consists of three cusps that develop in the embryonic stage. Unicuspid
aortic valve (UAV) is a rare congenital anomaly resulting in only one cusp with estimated
prevalence of 0.02% in general population. Aim of this study was to identify genetic
variants possibly associated with development of UAV. The study included 17 subjects,
namely 5 UAV patients and their healthy family members without UAV disorder. Total
DNA was isolated from venous blood samples and whole exomes sequencing (WES) was
performed using BGI’s WES protocol. Adapter-trimmed and quality-filtered reads (fastp)
were mapped to hg38 reference genome using BWA/SAMtools. VCF files were generated
using GATK (BaseRecalibrator, HaplotypeCaller) and annotated with InterVar and AnnoVar
tools. Rare heterozygous variants present in UAV patients were found in NOTCH1, TGFB2,
MYH6, EGFR, FBN2, C1R, ROBO4 and TBX5, genes associated with development of aortic
valves. Among these, most were missense mutations with damaging effects as predicted
using in silico tools (SIFT and/or Polyphen). Only mutation in MYH6 p.Ala1130Ser was
found in at least two different UAV patients. Also, rare homozygous missense mutation
p.Gly577Ser with high damaging potential was found in ADAMTS5 gene. Besides, highly
damaging heterozygous missense mutations were detected in gene interacting functional
partners (STRING) of genes associated with development of aortic valves: DVL1, THBS1,
NOTCH4, ADAMTS3, FBN1, NOTCH2, ADAM17, LRP5, WWTR1, C1S, ANKRD6 and TNNI1,
as well as homozygous in ACAN and KNG1. Taken together, malfunctions in ADAMTS5,
ACTA2, MYH6, FBN2, AXIN1, CELSR1 or TBX5 networks were found to be common in at
least two UAV patients, suggesting existence of genetic basis in UAV disorder, possibly as
a result of combined effects of multiple variants.",
publisher = "Belgrade : Institute of molecular genetics and genetic engineering",
journal = "4th Belgrade Bioinformatics Conference",
title = "Using whole exome sequencing to explore genetic basis of unicuspid aortic valve disease",
pages = "59-59",
volume = "4",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1999"
}
Mitić, M. M., Ušjak, D., Milošević, M., Cumbo, M., Dunjić Manevski, S., Tomić, B., Petrović, I., Otašević, P., Micović, S., Bojić, M.,& Đorđević, V.. (2023). Using whole exome sequencing to explore genetic basis of unicuspid aortic valve disease. in 4th Belgrade Bioinformatics Conference
Belgrade : Institute of molecular genetics and genetic engineering., 4, 59-59.
https://hdl.handle.net/21.15107/rcub_imagine_1999
Mitić MM, Ušjak D, Milošević M, Cumbo M, Dunjić Manevski S, Tomić B, Petrović I, Otašević P, Micović S, Bojić M, Đorđević V. Using whole exome sequencing to explore genetic basis of unicuspid aortic valve disease. in 4th Belgrade Bioinformatics Conference. 2023;4:59-59.
https://hdl.handle.net/21.15107/rcub_imagine_1999 .
Mitić, Martina Mia, Ušjak, Dušan, Milošević, Maja, Cumbo, Marija, Dunjić Manevski, Sofija, Tomić, Branko, Petrović, Ivana, Otašević, Petar, Micović, Slobodan, Bojić, Milovan, Đorđević, Valentina, "Using whole exome sequencing to explore genetic basis of unicuspid aortic valve disease" in 4th Belgrade Bioinformatics Conference, 4 (2023):59-59,
https://hdl.handle.net/21.15107/rcub_imagine_1999 .

STRENGTHENING THE NEXT-GENERATION SEQUENCING AND BIOINFORMATICS CAPACITIES IN THE REPUBLIC OF SERBIA

Divac Rankov, Aleksandra; Kušić-Tišma, Jelena; Đorđević, Valentina

(Macedonian Academy of Sciences and Arts, 2023)

TY  - CONF
AU  - Divac Rankov, Aleksandra
AU  - Kušić-Tišma, Jelena
AU  - Đorđević, Valentina
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2177
AB  - Bioinformatics was established at the IMGGE
in collaboration with the Beijing Genomics Institute
(BGI) and with the support of the Government of
the Republic of Serbia. The Center was founded
with the aim of accelerating the implementation
of 4P medicine (Preventive, Predictive, Personalized,
and Participatory), in our country by using the
cutting-edge tools of molecular biology and information
technology. As such, the center is unique in
Serbia and the South East Europe region.
The state-of-the-art equipment existing at the
Center (DNBSEQ-G400 (BGI), NextSeq 550Dx,
2000 and MiSeq (Illumina) Sequencing Systems;
MinION (OxfordNanopore); MGISP-9600
High-throughput Automated Sample Preparation
System) offered a wide range of application: the
whole genome and whole exome sequencing, targeted
sequencing, transcriptome sequencing and
more. The analysis of data was facilitated by the
access to the National Platform for Artificial Intelligence providing space for secure data storage, and
to a supercomputer (Nvidia), critical for processing
and analyzing Big Data.
Since its establishment more than 2000
SARS-CoV2 genomes were sequenced, 300 patient
samples undervent diagnostic work-up. Pilot project
for NIFTYPro screening was finished encompasing
58 pregnant women. First transcriptomes
and metagenomes were analyzed.
Further implementation of NGS methodology
in research and for diagnostics, and intensive
development of bioinformatics, by strengthening
the hardware and software capacities and the education
of the bioinformatics team, will lead us in
becoming driving force of the development of biomedicine
and biotechnology in Serbia, extending
collaboration beyond our borders.
PB  - Macedonian Academy of Sciences and Arts
C3  - International Journal of Medical Genetics
T1  - STRENGTHENING THE NEXT-GENERATION SEQUENCING AND BIOINFORMATICS CAPACITIES IN THE REPUBLIC OF SERBIA
EP  - 75
IS  - Supplement
SP  - 75
VL  - 26
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2177
ER  - 
@conference{
author = "Divac Rankov, Aleksandra and Kušić-Tišma, Jelena and Đorđević, Valentina",
year = "2023",
abstract = "Bioinformatics was established at the IMGGE
in collaboration with the Beijing Genomics Institute
(BGI) and with the support of the Government of
the Republic of Serbia. The Center was founded
with the aim of accelerating the implementation
of 4P medicine (Preventive, Predictive, Personalized,
and Participatory), in our country by using the
cutting-edge tools of molecular biology and information
technology. As such, the center is unique in
Serbia and the South East Europe region.
The state-of-the-art equipment existing at the
Center (DNBSEQ-G400 (BGI), NextSeq 550Dx,
2000 and MiSeq (Illumina) Sequencing Systems;
MinION (OxfordNanopore); MGISP-9600
High-throughput Automated Sample Preparation
System) offered a wide range of application: the
whole genome and whole exome sequencing, targeted
sequencing, transcriptome sequencing and
more. The analysis of data was facilitated by the
access to the National Platform for Artificial Intelligence providing space for secure data storage, and
to a supercomputer (Nvidia), critical for processing
and analyzing Big Data.
Since its establishment more than 2000
SARS-CoV2 genomes were sequenced, 300 patient
samples undervent diagnostic work-up. Pilot project
for NIFTYPro screening was finished encompasing
58 pregnant women. First transcriptomes
and metagenomes were analyzed.
Further implementation of NGS methodology
in research and for diagnostics, and intensive
development of bioinformatics, by strengthening
the hardware and software capacities and the education
of the bioinformatics team, will lead us in
becoming driving force of the development of biomedicine
and biotechnology in Serbia, extending
collaboration beyond our borders.",
publisher = "Macedonian Academy of Sciences and Arts",
journal = "International Journal of Medical Genetics",
title = "STRENGTHENING THE NEXT-GENERATION SEQUENCING AND BIOINFORMATICS CAPACITIES IN THE REPUBLIC OF SERBIA",
pages = "75-75",
number = "Supplement",
volume = "26",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2177"
}
Divac Rankov, A., Kušić-Tišma, J.,& Đorđević, V.. (2023). STRENGTHENING THE NEXT-GENERATION SEQUENCING AND BIOINFORMATICS CAPACITIES IN THE REPUBLIC OF SERBIA. in International Journal of Medical Genetics
Macedonian Academy of Sciences and Arts., 26(Supplement), 75-75.
https://hdl.handle.net/21.15107/rcub_imagine_2177
Divac Rankov A, Kušić-Tišma J, Đorđević V. STRENGTHENING THE NEXT-GENERATION SEQUENCING AND BIOINFORMATICS CAPACITIES IN THE REPUBLIC OF SERBIA. in International Journal of Medical Genetics. 2023;26(Supplement):75-75.
https://hdl.handle.net/21.15107/rcub_imagine_2177 .
Divac Rankov, Aleksandra, Kušić-Tišma, Jelena, Đorđević, Valentina, "STRENGTHENING THE NEXT-GENERATION SEQUENCING AND BIOINFORMATICS CAPACITIES IN THE REPUBLIC OF SERBIA" in International Journal of Medical Genetics, 26, no. Supplement (2023):75-75,
https://hdl.handle.net/21.15107/rcub_imagine_2177 .

Reconstitution of non-carrier, heterozygous and homozygous prothrombin belgrade mutation carrier plasma using recombinant proteins

Dunjić Manevski, Sofija; Cumbo, Marija; Gvozdenov, Maja; Tomić, Branko; Ušjak, Dušan; Đorđević, Valentina

(Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade, 2023)

TY  - CONF
AU  - Dunjić Manevski, Sofija
AU  - Cumbo, Marija
AU  - Gvozdenov, Maja
AU  - Tomić, Branko
AU  - Ušjak, Dušan
AU  - Đorđević, Valentina
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2123
AB  - Introduction: The prothrombin Belgrade variant (c.1787G>A, p.Arg596Gln) is a rare mutation found in
Serbia, Japan, China, America, India and leads to antithrombin resistance. Prothrombin Belgrade mutation influencesthrombin-antithrombin interactions and leadsto impaired inactivation of mutated thrombin. Also, it affectssodium binding site in thrombin, which isimportant forswitching from fast thrombin
configuration (coagulant properties) to slow configuration (anticoagulant properties). It has only been
found in a heterozygous state, which could mean that homozygous carriers are incompatible with life.
By using prothrombin (FII) deficient plasma, we could reconstitute plasma of wild type, heterozygous and
homozygous carrier, which could give more insight into the mechanism of this mutation.
Methods: Recombinant wild type and mutated prothrombin were generated by transient transfection
in HEK293T cell line. Western blot analysis was performed to test the efficiency of transfection. Human
Prothrombin ELISA (Nordic BioSite, Sweden) was used in order to measure recombinant prothrombin
concentration. Overall Hemostasis Potential (OHP) assay was performed to assess recombinant protein
activity. Recombinant wild type and mutated prothrombin were added to FII deficient plasma (Siemens,
Germany) in order to create reconstituted plasma, in the final concentration of 0.1 mg/mL, as it is approximately the level of prothrombin in human plasma.
Results: Reconstituted plasma samples that correspond to non-carrier, heterozygous carrier, and homozygous mutation carrier plasma were reconstructed. Recombinant proteinstested by OHP assay were
functional.
Conclusion: Reconstituted plasma samples allow us to examine the mechanism of prothrombin Belgrade mutation in various assays and in homozygous form as well.
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - Reconstitution of non-carrier, heterozygous and homozygous prothrombin belgrade mutation carrier plasma using recombinant proteins
EP  - 71
SP  - 71
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2123
ER  - 
@conference{
author = "Dunjić Manevski, Sofija and Cumbo, Marija and Gvozdenov, Maja and Tomić, Branko and Ušjak, Dušan and Đorđević, Valentina",
year = "2023",
abstract = "Introduction: The prothrombin Belgrade variant (c.1787G>A, p.Arg596Gln) is a rare mutation found in
Serbia, Japan, China, America, India and leads to antithrombin resistance. Prothrombin Belgrade mutation influencesthrombin-antithrombin interactions and leadsto impaired inactivation of mutated thrombin. Also, it affectssodium binding site in thrombin, which isimportant forswitching from fast thrombin
configuration (coagulant properties) to slow configuration (anticoagulant properties). It has only been
found in a heterozygous state, which could mean that homozygous carriers are incompatible with life.
By using prothrombin (FII) deficient plasma, we could reconstitute plasma of wild type, heterozygous and
homozygous carrier, which could give more insight into the mechanism of this mutation.
Methods: Recombinant wild type and mutated prothrombin were generated by transient transfection
in HEK293T cell line. Western blot analysis was performed to test the efficiency of transfection. Human
Prothrombin ELISA (Nordic BioSite, Sweden) was used in order to measure recombinant prothrombin
concentration. Overall Hemostasis Potential (OHP) assay was performed to assess recombinant protein
activity. Recombinant wild type and mutated prothrombin were added to FII deficient plasma (Siemens,
Germany) in order to create reconstituted plasma, in the final concentration of 0.1 mg/mL, as it is approximately the level of prothrombin in human plasma.
Results: Reconstituted plasma samples that correspond to non-carrier, heterozygous carrier, and homozygous mutation carrier plasma were reconstructed. Recombinant proteinstested by OHP assay were
functional.
Conclusion: Reconstituted plasma samples allow us to examine the mechanism of prothrombin Belgrade mutation in various assays and in homozygous form as well.",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "Reconstitution of non-carrier, heterozygous and homozygous prothrombin belgrade mutation carrier plasma using recombinant proteins",
pages = "71-71",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2123"
}
Dunjić Manevski, S., Cumbo, M., Gvozdenov, M., Tomić, B., Ušjak, D.,& Đorđević, V.. (2023). Reconstitution of non-carrier, heterozygous and homozygous prothrombin belgrade mutation carrier plasma using recombinant proteins. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 71-71.
https://hdl.handle.net/21.15107/rcub_imagine_2123
Dunjić Manevski S, Cumbo M, Gvozdenov M, Tomić B, Ušjak D, Đorđević V. Reconstitution of non-carrier, heterozygous and homozygous prothrombin belgrade mutation carrier plasma using recombinant proteins. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:71-71.
https://hdl.handle.net/21.15107/rcub_imagine_2123 .
Dunjić Manevski, Sofija, Cumbo, Marija, Gvozdenov, Maja, Tomić, Branko, Ušjak, Dušan, Đorđević, Valentina, "Reconstitution of non-carrier, heterozygous and homozygous prothrombin belgrade mutation carrier plasma using recombinant proteins" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):71-71,
https://hdl.handle.net/21.15107/rcub_imagine_2123 .

Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease

Stanković, Marija; Đorđević, Valentina; Tomović, Valentina; Nagorni-Obradović, Ljudmila; Petrović-Stanojević, Nataša; Kovač, Mirjana; Radojković, Dragica

(Belgrade : Society of Medical Biochemists of Serbia, 2023)

TY  - JOUR
AU  - Stanković, Marija
AU  - Đorđević, Valentina
AU  - Tomović, Valentina
AU  - Nagorni-Obradović, Ljudmila
AU  - Petrović-Stanojević, Nataša
AU  - Kovač, Mirjana
AU  - Radojković, Dragica
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1654
AB  - Background: Chronic  obstructive  pulmonary  disease(COPD) is a complex disorder with unexplained heritability.Interactions  of  genetic  and  environmental  factors  arethought  to  be  crucial  in  COPD.  So,  we  aim  to  examineinteractions of the endothelial nitric oxide synthase (eNOS)and angiotensin converting enzyme (ACE) genes and ciga-rette smoking in COPD. Methods:The  eNOS  G894T  and  ACE  ID  variants  wereanalyzed  in  122  COPD  patients  and  200  controls  fromSerbia. The effect of the variants on COPD was assessed bylogistic  regression.  Interactions  between  eNOS,  ACE  andcigarette  smoking  in  COPD  were  evaluated  using  a  case-control model. Interaction between the genes was analyzedin silico. Results:No effect of the eNOS G894T and ACE ID variantson  COPD  was  found  in  our  study.  Gene-gene  interactionbetween  the  eNOS  TT  and  ACE  D  was  identified(p=0.033) in COPD. The interaction is realized within the complex network of biochemical pathways. Gene-environ-ment  interactions  between  the  eNOS  T  and  cigarettesmoking (p=0.013), and the ACE II and cigarette smoking(p=0.009) were detected in COPD in our study. Conclusions:This is the first research to reveal interactionsof  the  eNOS  and  ACE  genes  and  cigarette  smoking  inCOPD progressing our understanding of COPD heritabilityand contributing to the development of appropriate treat-ments.
AB  - Uvod: Hronična opstruktivna bolest pluća (HOBP) je složeno oboljenje sa nerazjašnjenom genetičkom osnovom.Smatra se da su interakcije genetskih i spoljašnjih faktora ključne u HOBP. Stoga je naš cilj bio da ispitamo interakcijegena za endotelijalnu azot-monoksid sintazu (eNOS) i angiotenzin konvertujući enzim (ACE) i duvanskog dima uHOBP. Metode :eNOS G894T i ACE ID varijante su analiziranekod 122 HOBP pacijenta i 200 kontrola iz Srbije. Uticajvarijanti na HOBP je ispitan logističkom regresijom. Interakcije izme|u eNOS, ACE i duvanskog dima u HOBP suispitane korišćenjem modela slučaj-kontrola. Interakciaja između gena je analizirana in silico. Rezultati: Prema ovoj studiji eNOS G894T i ACE ID varijante nemaju uticaj na HOBP. Gen-gen interakcija između eNOS TT i ACE D je identifikovana (p=0,033) u HOBP.Ova interakcija se ostvaruje u okviru složene mreže bio-hemijskih puteva. Gen-sredina interakcije izme|u eNOS Ti duvanskog dima (p=0,013), i ACE II i duvanskog dima(p=0,009) su detektovane u HOBP u ovoj studiji.Zaključak: Ovo je prvo istraživanje u kome su otkriveneinterakcije između eNOS i ACE gena i duvanskog dima uHOBP što doprinosi našem razumevanju genetičke osnove HOBP i razvoju adekvatnog tretmana.
PB  - Belgrade : Society of Medical Biochemists of Serbia
T2  - Journal of Medical Biochemistry
T1  - Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease
T1  - Interakcije eNOS i ACE gena i duvanskog dima u hroničnoj opstruktivnoj bolesti pluća
EP  - 104
IS  - 1
SP  - 94
VL  - 41
DO  - 10.5937/jomb0-34017
ER  - 
@article{
author = "Stanković, Marija and Đorđević, Valentina and Tomović, Valentina and Nagorni-Obradović, Ljudmila and Petrović-Stanojević, Nataša and Kovač, Mirjana and Radojković, Dragica",
year = "2023",
abstract = "Background: Chronic  obstructive  pulmonary  disease(COPD) is a complex disorder with unexplained heritability.Interactions  of  genetic  and  environmental  factors  arethought  to  be  crucial  in  COPD.  So,  we  aim  to  examineinteractions of the endothelial nitric oxide synthase (eNOS)and angiotensin converting enzyme (ACE) genes and ciga-rette smoking in COPD. Methods:The  eNOS  G894T  and  ACE  ID  variants  wereanalyzed  in  122  COPD  patients  and  200  controls  fromSerbia. The effect of the variants on COPD was assessed bylogistic  regression.  Interactions  between  eNOS,  ACE  andcigarette  smoking  in  COPD  were  evaluated  using  a  case-control model. Interaction between the genes was analyzedin silico. Results:No effect of the eNOS G894T and ACE ID variantson  COPD  was  found  in  our  study.  Gene-gene  interactionbetween  the  eNOS  TT  and  ACE  D  was  identified(p=0.033) in COPD. The interaction is realized within the complex network of biochemical pathways. Gene-environ-ment  interactions  between  the  eNOS  T  and  cigarettesmoking (p=0.013), and the ACE II and cigarette smoking(p=0.009) were detected in COPD in our study. Conclusions:This is the first research to reveal interactionsof  the  eNOS  and  ACE  genes  and  cigarette  smoking  inCOPD progressing our understanding of COPD heritabilityand contributing to the development of appropriate treat-ments., Uvod: Hronična opstruktivna bolest pluća (HOBP) je složeno oboljenje sa nerazjašnjenom genetičkom osnovom.Smatra se da su interakcije genetskih i spoljašnjih faktora ključne u HOBP. Stoga je naš cilj bio da ispitamo interakcijegena za endotelijalnu azot-monoksid sintazu (eNOS) i angiotenzin konvertujući enzim (ACE) i duvanskog dima uHOBP. Metode :eNOS G894T i ACE ID varijante su analiziranekod 122 HOBP pacijenta i 200 kontrola iz Srbije. Uticajvarijanti na HOBP je ispitan logističkom regresijom. Interakcije izme|u eNOS, ACE i duvanskog dima u HOBP suispitane korišćenjem modela slučaj-kontrola. Interakciaja između gena je analizirana in silico. Rezultati: Prema ovoj studiji eNOS G894T i ACE ID varijante nemaju uticaj na HOBP. Gen-gen interakcija između eNOS TT i ACE D je identifikovana (p=0,033) u HOBP.Ova interakcija se ostvaruje u okviru složene mreže bio-hemijskih puteva. Gen-sredina interakcije izme|u eNOS Ti duvanskog dima (p=0,013), i ACE II i duvanskog dima(p=0,009) su detektovane u HOBP u ovoj studiji.Zaključak: Ovo je prvo istraživanje u kome su otkriveneinterakcije između eNOS i ACE gena i duvanskog dima uHOBP što doprinosi našem razumevanju genetičke osnove HOBP i razvoju adekvatnog tretmana.",
publisher = "Belgrade : Society of Medical Biochemists of Serbia",
journal = "Journal of Medical Biochemistry",
title = "Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease, Interakcije eNOS i ACE gena i duvanskog dima u hroničnoj opstruktivnoj bolesti pluća",
pages = "104-94",
number = "1",
volume = "41",
doi = "10.5937/jomb0-34017"
}
Stanković, M., Đorđević, V., Tomović, V., Nagorni-Obradović, L., Petrović-Stanojević, N., Kovač, M.,& Radojković, D.. (2023). Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease. in Journal of Medical Biochemistry
Belgrade : Society of Medical Biochemists of Serbia., 41(1), 94-104.
https://doi.org/10.5937/jomb0-34017
Stanković M, Đorđević V, Tomović V, Nagorni-Obradović L, Petrović-Stanojević N, Kovač M, Radojković D. Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease. in Journal of Medical Biochemistry. 2023;41(1):94-104.
doi:10.5937/jomb0-34017 .
Stanković, Marija, Đorđević, Valentina, Tomović, Valentina, Nagorni-Obradović, Ljudmila, Petrović-Stanojević, Nataša, Kovač, Mirjana, Radojković, Dragica, "Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease" in Journal of Medical Biochemistry, 41, no. 1 (2023):94-104,
https://doi.org/10.5937/jomb0-34017 . .
1

Targeting outer membrane protein A (OmpA) – inhibitory effect of 2′-hydroxychalcone derivatives on Acinetobacter baumannii and Candida albicans dual-species biofilm formation

Ušjak, Dušan; Novović, Katarina; Ivković, Branka; Tomić, Branko; Đorđević, Valentina; Milenković, Marina

(2023)

TY  - JOUR
AU  - Ušjak, Dušan
AU  - Novović, Katarina
AU  - Ivković, Branka
AU  - Tomić, Branko
AU  - Đorđević, Valentina
AU  - Milenković, Marina
PY  - 2023
UR  - https://doi.org/10.1080/08927014.2023.2215693
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1896
AB  - Biofilm production facilitates microbial colonization of wounds and catheters. Acinetobacter baumannii produces high levels of biofilm and causes difficult-to-treat nosocomial infections. Candida albicans is another strong biofilm producer which may facilitate A. baumannii adhesion by providing hyphae-mediated OmpA-binding sites. Here we tested the potential of 2′-hydroxychalcones to inhibit dual-species biofilm production of A. baumannii and Candida spp., and further predicted the mechanism of structure-related difference in activity. The results suggest that 2′-hydroxychalcones exhibit potent activity against Candida spp./A. baumannii dual-species biofilm production. Particularly active was trifluoromethyl-substituted derivative (p-CF3), which decreased C. albicans/A. baumannii biomass produced on vein-indwelling parts of the central venous catheterization set by up to 99%. Further, higher OmpA-binding affinity was also calculated for p-CF3, which together with demonstrated significant ompA-downregulating activity, suggests that superior antibiofilm activity of this chalcone against the tested dual-species community of A. baumannii is mediated through the OmpA.
T2  - Biofouling
T2  - Biofouling
T1  - Targeting outer membrane protein A (OmpA) – inhibitory effect of 2′-hydroxychalcone derivatives on Acinetobacter baumannii and Candida albicans dual-species biofilm formation
EP  - 11
SP  - 1
DO  - 10.1080/08927014.2023.2215693
ER  - 
@article{
author = "Ušjak, Dušan and Novović, Katarina and Ivković, Branka and Tomić, Branko and Đorđević, Valentina and Milenković, Marina",
year = "2023",
abstract = "Biofilm production facilitates microbial colonization of wounds and catheters. Acinetobacter baumannii produces high levels of biofilm and causes difficult-to-treat nosocomial infections. Candida albicans is another strong biofilm producer which may facilitate A. baumannii adhesion by providing hyphae-mediated OmpA-binding sites. Here we tested the potential of 2′-hydroxychalcones to inhibit dual-species biofilm production of A. baumannii and Candida spp., and further predicted the mechanism of structure-related difference in activity. The results suggest that 2′-hydroxychalcones exhibit potent activity against Candida spp./A. baumannii dual-species biofilm production. Particularly active was trifluoromethyl-substituted derivative (p-CF3), which decreased C. albicans/A. baumannii biomass produced on vein-indwelling parts of the central venous catheterization set by up to 99%. Further, higher OmpA-binding affinity was also calculated for p-CF3, which together with demonstrated significant ompA-downregulating activity, suggests that superior antibiofilm activity of this chalcone against the tested dual-species community of A. baumannii is mediated through the OmpA.",
journal = "Biofouling, Biofouling",
title = "Targeting outer membrane protein A (OmpA) – inhibitory effect of 2′-hydroxychalcone derivatives on Acinetobacter baumannii and Candida albicans dual-species biofilm formation",
pages = "11-1",
doi = "10.1080/08927014.2023.2215693"
}
Ušjak, D., Novović, K., Ivković, B., Tomić, B., Đorđević, V.,& Milenković, M.. (2023). Targeting outer membrane protein A (OmpA) – inhibitory effect of 2′-hydroxychalcone derivatives on Acinetobacter baumannii and Candida albicans dual-species biofilm formation. in Biofouling, 1-11.
https://doi.org/10.1080/08927014.2023.2215693
Ušjak D, Novović K, Ivković B, Tomić B, Đorđević V, Milenković M. Targeting outer membrane protein A (OmpA) – inhibitory effect of 2′-hydroxychalcone derivatives on Acinetobacter baumannii and Candida albicans dual-species biofilm formation. in Biofouling. 2023;:1-11.
doi:10.1080/08927014.2023.2215693 .
Ušjak, Dušan, Novović, Katarina, Ivković, Branka, Tomić, Branko, Đorđević, Valentina, Milenković, Marina, "Targeting outer membrane protein A (OmpA) – inhibitory effect of 2′-hydroxychalcone derivatives on Acinetobacter baumannii and Candida albicans dual-species biofilm formation" in Biofouling (2023):1-11,
https://doi.org/10.1080/08927014.2023.2215693 . .
2
1
1

Genomic Surveillance and Phylogenetic Analysis of SARS-CoV-2 Variants in Serbia: Insights into Evolutionary Dynamics and Genetic Diversity

Novković, Mirjana; Banović Đeri, Bojana; Todorović, Saša; Đorđević, Valentina

(Belgrade : Institute of molecular genetics and genetic engineering, 2023)

TY  - CONF
AU  - Novković, Mirjana
AU  - Banović Đeri, Bojana
AU  - Todorović, Saša
AU  - Đorđević, Valentina
PY  - 2023
UR  - https://belbi.bg.ac.rs/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2021
AB  - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global
pandemic, resulting in significant morbidity and mortality worldwide. Understanding the evolutionary
dynamics and genetic diversity of the virus were crucial for virus control and management
strategies. With that aim we conducted genomic surveillance and phylogenetic analysis of
SARS-CoV-2 variants in Serbia, spanning from March 2020 to the end of January 2023.
Sequencing was conducted using three different platforms: Oxford Nanopore, Ion Torrent AmpliSeq
and BGISEQ-500. Consensus sequences obtained using platforms respective software were deposited
in the GISAID database. In this study 2109 good-quality sequences were included (doi.10.55876/
gis8.230411qh). Pangolin and Nextclade software were utilized for clade, lineage and variant
determination, while sequence alignment and construction of the phylogenetic tree was performed
using Nextstrain web-based application.
Variant analysis revealed over 125,000 mutations across the 2109 sequences, of which 38% occurred in
the S protein encoding gene. The most common mutations involved intragenic single nucleotide variants
(88%), followed by intragenic deletions (5%). All sequences were assigned to following 16 clades: 20A,
20B, 20C, 20D, 20E, 20G, 20I, 21J, 21K, 21L, 22A, 22B, 22C, 22D, 22E, and 22F.
Temporal analysis of the variants in Serbia revealed that the Alpha variant was predominant during 2020
and the first three months of 2021. The Delta variant emerged in June 2021, dominating until the end
of December 2021, when Omicron variant was detected for the first time, overtaking the dominance for
the remaining surveillance period. Notably, the Gamma and Epsilon variants were not detected in the
analyzed samples.
Phylogenetic analysis demonstrated that the SARS-CoV-2 variants circulating in Serbia were largely
comparable to the variants found in Europe. However, a slight delay in their emergence was observed,
potentially attributed to a lower travel rate during that period and a decreased frequency of sequencing
in certain months.
PB  - Belgrade : Institute of molecular genetics and genetic engineering
C3  - 4th Belgrade Bioinformatics Conference
T1  - Genomic Surveillance and Phylogenetic Analysis of SARS-CoV-2 Variants in Serbia: Insights into Evolutionary Dynamics and Genetic Diversity
EP  - 81
SP  - 81
VL  - 4
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2021
ER  - 
@conference{
author = "Novković, Mirjana and Banović Đeri, Bojana and Todorović, Saša and Đorđević, Valentina",
year = "2023",
abstract = "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global
pandemic, resulting in significant morbidity and mortality worldwide. Understanding the evolutionary
dynamics and genetic diversity of the virus were crucial for virus control and management
strategies. With that aim we conducted genomic surveillance and phylogenetic analysis of
SARS-CoV-2 variants in Serbia, spanning from March 2020 to the end of January 2023.
Sequencing was conducted using three different platforms: Oxford Nanopore, Ion Torrent AmpliSeq
and BGISEQ-500. Consensus sequences obtained using platforms respective software were deposited
in the GISAID database. In this study 2109 good-quality sequences were included (doi.10.55876/
gis8.230411qh). Pangolin and Nextclade software were utilized for clade, lineage and variant
determination, while sequence alignment and construction of the phylogenetic tree was performed
using Nextstrain web-based application.
Variant analysis revealed over 125,000 mutations across the 2109 sequences, of which 38% occurred in
the S protein encoding gene. The most common mutations involved intragenic single nucleotide variants
(88%), followed by intragenic deletions (5%). All sequences were assigned to following 16 clades: 20A,
20B, 20C, 20D, 20E, 20G, 20I, 21J, 21K, 21L, 22A, 22B, 22C, 22D, 22E, and 22F.
Temporal analysis of the variants in Serbia revealed that the Alpha variant was predominant during 2020
and the first three months of 2021. The Delta variant emerged in June 2021, dominating until the end
of December 2021, when Omicron variant was detected for the first time, overtaking the dominance for
the remaining surveillance period. Notably, the Gamma and Epsilon variants were not detected in the
analyzed samples.
Phylogenetic analysis demonstrated that the SARS-CoV-2 variants circulating in Serbia were largely
comparable to the variants found in Europe. However, a slight delay in their emergence was observed,
potentially attributed to a lower travel rate during that period and a decreased frequency of sequencing
in certain months.",
publisher = "Belgrade : Institute of molecular genetics and genetic engineering",
journal = "4th Belgrade Bioinformatics Conference",
title = "Genomic Surveillance and Phylogenetic Analysis of SARS-CoV-2 Variants in Serbia: Insights into Evolutionary Dynamics and Genetic Diversity",
pages = "81-81",
volume = "4",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2021"
}
Novković, M., Banović Đeri, B., Todorović, S.,& Đorđević, V.. (2023). Genomic Surveillance and Phylogenetic Analysis of SARS-CoV-2 Variants in Serbia: Insights into Evolutionary Dynamics and Genetic Diversity. in 4th Belgrade Bioinformatics Conference
Belgrade : Institute of molecular genetics and genetic engineering., 4, 81-81.
https://hdl.handle.net/21.15107/rcub_imagine_2021
Novković M, Banović Đeri B, Todorović S, Đorđević V. Genomic Surveillance and Phylogenetic Analysis of SARS-CoV-2 Variants in Serbia: Insights into Evolutionary Dynamics and Genetic Diversity. in 4th Belgrade Bioinformatics Conference. 2023;4:81-81.
https://hdl.handle.net/21.15107/rcub_imagine_2021 .
Novković, Mirjana, Banović Đeri, Bojana, Todorović, Saša, Đorđević, Valentina, "Genomic Surveillance and Phylogenetic Analysis of SARS-CoV-2 Variants in Serbia: Insights into Evolutionary Dynamics and Genetic Diversity" in 4th Belgrade Bioinformatics Conference, 4 (2023):81-81,
https://hdl.handle.net/21.15107/rcub_imagine_2021 .

A phenotype driven integrative framework uncovers molecular mechanisms of a rare hereditary thrombophilia

Malod-Dognin, Noël; Ceddia, Gaia; Gvozdenov, Maja; Tomić, Branko; Manevski Dunjić, Sofija ; Đorđević, Valentina; Pržulj, Nataša

(2023)

TY  - JOUR
AU  - Malod-Dognin, Noël
AU  - Ceddia, Gaia
AU  - Gvozdenov, Maja
AU  - Tomić, Branko
AU  - Manevski Dunjić, Sofija 
AU  - Đorđević, Valentina
AU  - Pržulj, Nataša
PY  - 2023
UR  - https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0284084
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1920
AB  - Antithrombin resistance is a rare subtype of hereditary thrombophilia caused by prothrombin gene variants, leading to thrombotic disorders. Recently, the Prothrombin Belgrade variant has been reported as a specific variant that leads to antithrombin resistance in two Serbian families with thrombosis. However, due to clinical data scarcity and the inapplicability of traditional genome-wide association studies (GWAS), a broader perspective on molecular and phenotypic mechanisms associated with the Prothrombin Belgrade variant is yet to be uncovered. Here, we propose an integrative framework to address the lack of genomic samples and support the genomic signal from the full genome sequences of five heterozygous subjects by integrating it with subjects’ phenotypes and the genes’ molecular interactions. Our goal is to identify candidate thrombophilia-related genes for which our subjects possess germline variants by focusing on the resulting gene clusters of our integrative framework. We applied a Non-negative Matrix Tri-Factorization-based method to simultaneously integrate different data sources, taking into account the observed phenotypes. In other words, our data-integration framework reveals gene clusters involved with this rare disease by fusing different datasets. Our results are in concordance with the current literature about antithrombin resistance. We also found candidate disease-related genes that need to be further investigated. CD320, RTEL1, UCP2, APOA5 and PROZ participate in healthy-specific or disease-specific subnetworks involving thrombophilia-annotated genes and are related to general thrombophilia mechanisms according to the literature. Moreover, the ADRA2A and TBXA2R subnetworks analysis suggested that their variants may have a protective effect due to their connection with decreased platelet activation. The results show that our method can give insights into antithrombin resistance even if a small amount of genetic data is available. Our framework is also customizable, meaning that it applies to any other rare disease.
T2  - Plos one
T1  - A phenotype driven integrative framework uncovers molecular mechanisms of a rare hereditary thrombophilia
IS  - 4
SP  - e0284084
VL  - 18
DO  - 10.1371/journal.pone.0284084
ER  - 
@article{
author = "Malod-Dognin, Noël and Ceddia, Gaia and Gvozdenov, Maja and Tomić, Branko and Manevski Dunjić, Sofija  and Đorđević, Valentina and Pržulj, Nataša",
year = "2023",
abstract = "Antithrombin resistance is a rare subtype of hereditary thrombophilia caused by prothrombin gene variants, leading to thrombotic disorders. Recently, the Prothrombin Belgrade variant has been reported as a specific variant that leads to antithrombin resistance in two Serbian families with thrombosis. However, due to clinical data scarcity and the inapplicability of traditional genome-wide association studies (GWAS), a broader perspective on molecular and phenotypic mechanisms associated with the Prothrombin Belgrade variant is yet to be uncovered. Here, we propose an integrative framework to address the lack of genomic samples and support the genomic signal from the full genome sequences of five heterozygous subjects by integrating it with subjects’ phenotypes and the genes’ molecular interactions. Our goal is to identify candidate thrombophilia-related genes for which our subjects possess germline variants by focusing on the resulting gene clusters of our integrative framework. We applied a Non-negative Matrix Tri-Factorization-based method to simultaneously integrate different data sources, taking into account the observed phenotypes. In other words, our data-integration framework reveals gene clusters involved with this rare disease by fusing different datasets. Our results are in concordance with the current literature about antithrombin resistance. We also found candidate disease-related genes that need to be further investigated. CD320, RTEL1, UCP2, APOA5 and PROZ participate in healthy-specific or disease-specific subnetworks involving thrombophilia-annotated genes and are related to general thrombophilia mechanisms according to the literature. Moreover, the ADRA2A and TBXA2R subnetworks analysis suggested that their variants may have a protective effect due to their connection with decreased platelet activation. The results show that our method can give insights into antithrombin resistance even if a small amount of genetic data is available. Our framework is also customizable, meaning that it applies to any other rare disease.",
journal = "Plos one",
title = "A phenotype driven integrative framework uncovers molecular mechanisms of a rare hereditary thrombophilia",
number = "4",
pages = "e0284084",
volume = "18",
doi = "10.1371/journal.pone.0284084"
}
Malod-Dognin, N., Ceddia, G., Gvozdenov, M., Tomić, B., Manevski Dunjić, S., Đorđević, V.,& Pržulj, N.. (2023). A phenotype driven integrative framework uncovers molecular mechanisms of a rare hereditary thrombophilia. in Plos one, 18(4), e0284084.
https://doi.org/10.1371/journal.pone.0284084
Malod-Dognin N, Ceddia G, Gvozdenov M, Tomić B, Manevski Dunjić S, Đorđević V, Pržulj N. A phenotype driven integrative framework uncovers molecular mechanisms of a rare hereditary thrombophilia. in Plos one. 2023;18(4):e0284084.
doi:10.1371/journal.pone.0284084 .
Malod-Dognin, Noël, Ceddia, Gaia, Gvozdenov, Maja, Tomić, Branko, Manevski Dunjić, Sofija , Đorđević, Valentina, Pržulj, Nataša, "A phenotype driven integrative framework uncovers molecular mechanisms of a rare hereditary thrombophilia" in Plos one, 18, no. 4 (2023):e0284084,
https://doi.org/10.1371/journal.pone.0284084 . .
5

Prothrombin influences proliferation and migration of colon cancer in vitro

Cumbo, Marija; Tomić, Branko; Dunjić Manevski, Sofija; Gvozdenov, Maja; Ušjak, Dušan; Mitić, Martina Mia; Đorđević, Valentina

(Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade, 2023)

TY  - CONF
AU  - Cumbo, Marija
AU  - Tomić, Branko
AU  - Dunjić Manevski, Sofija
AU  - Gvozdenov, Maja
AU  - Ušjak, Dušan
AU  - Mitić, Martina Mia
AU  - Đorđević, Valentina
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2135
AB  - Introduction: Thrombin, crucial member of the coagulation cascade, can influence growth and development of different types of cancer. Prothrombin, thrombin precursor, although predominantly secreted
from the liver into the bloodstream, can also be expressed in the cancer cells. According to latest data prothrombin can bind in vitro to transmembrane receptors, which have previously been shown to be up-regulated in cancers and activate migration and invasion. Despite the significant amount of data on the
effects of thrombin in cancer progression, there are little data of prothrombin´s effect. The aim of this
study was to further examine the effects of prothrombin and thrombin in cancer cell lines.
Methods: Colon cancer cell lines (Caco2, SW480, SW620, HT29 and HCT116) were treated with prothrombin, thrombin and direct thrombin inhibitor, dabigatran, for 24h and 48h. To assess the effects of
treatment on cell viability and proliferation MTT test was used, and wound healing assay was used for cell
migration potential.
Results: Detected effects of treatment with prothrombin, thrombin and dabigatran varied between cell
lines. Trend of lower cell viability, proliferation and migration was observed in cells treated with prothrombin in comparison to untreated controls.
Conclusion: Our resultsindicate that prothrombin, although considered an inactive zymogen, can exert
an effect on colon cancer cells proliferation and migration in vitro.
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - Prothrombin influences proliferation and migration of colon cancer in vitro
EP  - 156
SP  - 156
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2135
ER  - 
@conference{
author = "Cumbo, Marija and Tomić, Branko and Dunjić Manevski, Sofija and Gvozdenov, Maja and Ušjak, Dušan and Mitić, Martina Mia and Đorđević, Valentina",
year = "2023",
abstract = "Introduction: Thrombin, crucial member of the coagulation cascade, can influence growth and development of different types of cancer. Prothrombin, thrombin precursor, although predominantly secreted
from the liver into the bloodstream, can also be expressed in the cancer cells. According to latest data prothrombin can bind in vitro to transmembrane receptors, which have previously been shown to be up-regulated in cancers and activate migration and invasion. Despite the significant amount of data on the
effects of thrombin in cancer progression, there are little data of prothrombin´s effect. The aim of this
study was to further examine the effects of prothrombin and thrombin in cancer cell lines.
Methods: Colon cancer cell lines (Caco2, SW480, SW620, HT29 and HCT116) were treated with prothrombin, thrombin and direct thrombin inhibitor, dabigatran, for 24h and 48h. To assess the effects of
treatment on cell viability and proliferation MTT test was used, and wound healing assay was used for cell
migration potential.
Results: Detected effects of treatment with prothrombin, thrombin and dabigatran varied between cell
lines. Trend of lower cell viability, proliferation and migration was observed in cells treated with prothrombin in comparison to untreated controls.
Conclusion: Our resultsindicate that prothrombin, although considered an inactive zymogen, can exert
an effect on colon cancer cells proliferation and migration in vitro.",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "Prothrombin influences proliferation and migration of colon cancer in vitro",
pages = "156-156",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2135"
}
Cumbo, M., Tomić, B., Dunjić Manevski, S., Gvozdenov, M., Ušjak, D., Mitić, M. M.,& Đorđević, V.. (2023). Prothrombin influences proliferation and migration of colon cancer in vitro. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 156-156.
https://hdl.handle.net/21.15107/rcub_imagine_2135
Cumbo M, Tomić B, Dunjić Manevski S, Gvozdenov M, Ušjak D, Mitić MM, Đorđević V. Prothrombin influences proliferation and migration of colon cancer in vitro. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:156-156.
https://hdl.handle.net/21.15107/rcub_imagine_2135 .
Cumbo, Marija, Tomić, Branko, Dunjić Manevski, Sofija, Gvozdenov, Maja, Ušjak, Dušan, Mitić, Martina Mia, Đorđević, Valentina, "Prothrombin influences proliferation and migration of colon cancer in vitro" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):156-156,
https://hdl.handle.net/21.15107/rcub_imagine_2135 .

Nasledni faktori rizika za trombofiliju – od tačkastih mutacija do primene veštačke inteligencije

Tomić, Branko; Gvozdenov, Maja; Cumbo, Marija; Dunjić Manevski, Sofija; Đorđević, Valentina

(Beograd : Srpsko biološko društvo, 2022)

TY  - CONF
AU  - Tomić, Branko
AU  - Gvozdenov, Maja
AU  - Cumbo, Marija
AU  - Dunjić Manevski, Sofija
AU  - Đorđević, Valentina
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1739
AB  - Trombofilija je patofiziološko stanje povećanog rizika za nastanak
hiperkoagulacije, koja može dovesti do začepljenja krvnog suda (tromboze).
Faktori rizika za nastanak ove multifaktorijalne bolesti mogu biti sredinski,
uzrokovani načinom života, i nasledni (genetski). Do sada je identifikovan
veliki broj naslednih faktora rizika, uglavnom tačkastih mutacija u genima za
proteine hemostaznog sistema. Iako se ove mutacije analiziraju u okviru
rutinskih kliničkih testova, kod značajnog broja bolesnika i nakon sprovedenih
dijagnostičkih procedura, uzrok trombotičkog događaja ostaje nepoznat, što
implicira postojanje neidentifikovanih naslednih faktora rizika. U cilju
njihove identifikacije, vrše se dalje genske analize, asocijativne studije,
karakterizacije potencijalnih faktora rizika u in vitro i in vivo studijama na
različitim model sistemima. U našem dosadašnjem radu detektovano je više
varijanti u kodirajućem i nekodirajućem regionu gena, za koje je karakterizacijom
utvrđeno da utiču na ekspresiju i/ili funcionalnost koagulacionih proteina.
Primenom sekvenciranja nove generacije i bioinformatičke obrade, omogućena je
sveobuhvatnija analiza celokupnog genoma i identifikacija klastera gena koji su
povezani sa kompleksnom kliničkom slikom tromboza. Kombinovanjem velikog
broja podataka o genetskim i sredinskim faktorima, primenom veštačke
inteligencije, otvara se mogućnost kompletnijeg sagledavanja mehanizama
trombofilije i multifaktorijalnih bolesti uopšte.
AB  - Тромбофилија је патофизиолошко стање повећаног ризика за настанак
хиперкоагулације, која може довести до зачепљења крвног суда (тромбозе).
Фактори ризика за настанак ове мултифакторијалне болести могу бити средински,
узроковани начином живота, и наследни (генетски). До сада је идентификован
велики број наследних фактора ризика, углавном тачкастих мутација у генима за
протеине хемостазног система. Иако се ове мутације анализирају у оквиру
рутинских клиничких тестова, код значајног броја болесника и након спроведених
дијагностичких процедура, узрок тромботичког догађаја остаје непознат, што
имплицира постојање неидентификованих наследних фактора ризика. У циљу
њихове идентификације, врше се даље генске анализе, асоцијативне студије,
карактеризације потенцијалних фактора ризика у in vitro и in vivo студијама на
различитим модел системима. У нашем досадашњем раду детектовано је више
варијанти у кодирајућем и некодирајућем региону гена, за које је карактеризацијом
утврђено да утичу на експресију и/или фунционалност коагулационих протеина.
Применом секвенцирања нове генерације и биоинформатичке обраде, омогућена је
свеобухватнија анализа целокупног генома и идентификација кластера гена који су
повезани са комплексном клиничком сликом тромбоза. Комбиновањем великог
броја података о генетским и срединским факторима, применом вештачке
интелигенције, отвара се могућност комплетнијег сагледавања механизама
тромбофилије и мултифакторијалних болести уопште.
PB  - Beograd : Srpsko biološko društvo
C3  - Treći kongres biologa Srbije
T1  - Nasledni faktori rizika za trombofiliju – od tačkastih mutacija do primene veštačke inteligencije
T1  - Наследни фактори ризика за тромбофилију – од тачкастих мутација до примене вештачке интелигенције
SP  - 278
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1739
ER  - 
@conference{
author = "Tomić, Branko and Gvozdenov, Maja and Cumbo, Marija and Dunjić Manevski, Sofija and Đorđević, Valentina",
year = "2022",
abstract = "Trombofilija je patofiziološko stanje povećanog rizika za nastanak
hiperkoagulacije, koja može dovesti do začepljenja krvnog suda (tromboze).
Faktori rizika za nastanak ove multifaktorijalne bolesti mogu biti sredinski,
uzrokovani načinom života, i nasledni (genetski). Do sada je identifikovan
veliki broj naslednih faktora rizika, uglavnom tačkastih mutacija u genima za
proteine hemostaznog sistema. Iako se ove mutacije analiziraju u okviru
rutinskih kliničkih testova, kod značajnog broja bolesnika i nakon sprovedenih
dijagnostičkih procedura, uzrok trombotičkog događaja ostaje nepoznat, što
implicira postojanje neidentifikovanih naslednih faktora rizika. U cilju
njihove identifikacije, vrše se dalje genske analize, asocijativne studije,
karakterizacije potencijalnih faktora rizika u in vitro i in vivo studijama na
različitim model sistemima. U našem dosadašnjem radu detektovano je više
varijanti u kodirajućem i nekodirajućem regionu gena, za koje je karakterizacijom
utvrđeno da utiču na ekspresiju i/ili funcionalnost koagulacionih proteina.
Primenom sekvenciranja nove generacije i bioinformatičke obrade, omogućena je
sveobuhvatnija analiza celokupnog genoma i identifikacija klastera gena koji su
povezani sa kompleksnom kliničkom slikom tromboza. Kombinovanjem velikog
broja podataka o genetskim i sredinskim faktorima, primenom veštačke
inteligencije, otvara se mogućnost kompletnijeg sagledavanja mehanizama
trombofilije i multifaktorijalnih bolesti uopšte., Тромбофилија је патофизиолошко стање повећаног ризика за настанак
хиперкоагулације, која може довести до зачепљења крвног суда (тромбозе).
Фактори ризика за настанак ове мултифакторијалне болести могу бити средински,
узроковани начином живота, и наследни (генетски). До сада је идентификован
велики број наследних фактора ризика, углавном тачкастих мутација у генима за
протеине хемостазног система. Иако се ове мутације анализирају у оквиру
рутинских клиничких тестова, код значајног броја болесника и након спроведених
дијагностичких процедура, узрок тромботичког догађаја остаје непознат, што
имплицира постојање неидентификованих наследних фактора ризика. У циљу
њихове идентификације, врше се даље генске анализе, асоцијативне студије,
карактеризације потенцијалних фактора ризика у in vitro и in vivo студијама на
различитим модел системима. У нашем досадашњем раду детектовано је више
варијанти у кодирајућем и некодирајућем региону гена, за које је карактеризацијом
утврђено да утичу на експресију и/или фунционалност коагулационих протеина.
Применом секвенцирања нове генерације и биоинформатичке обраде, омогућена је
свеобухватнија анализа целокупног генома и идентификација кластера гена који су
повезани са комплексном клиничком сликом тромбоза. Комбиновањем великог
броја података о генетским и срединским факторима, применом вештачке
интелигенције, отвара се могућност комплетнијег сагледавања механизама
тромбофилије и мултифакторијалних болести уопште.",
publisher = "Beograd : Srpsko biološko društvo",
journal = "Treći kongres biologa Srbije",
title = "Nasledni faktori rizika za trombofiliju – od tačkastih mutacija do primene veštačke inteligencije, Наследни фактори ризика за тромбофилију – од тачкастих мутација до примене вештачке интелигенције",
pages = "278",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1739"
}
Tomić, B., Gvozdenov, M., Cumbo, M., Dunjić Manevski, S.,& Đorđević, V.. (2022). Nasledni faktori rizika za trombofiliju – od tačkastih mutacija do primene veštačke inteligencije. in Treći kongres biologa Srbije
Beograd : Srpsko biološko društvo., 278.
https://hdl.handle.net/21.15107/rcub_imagine_1739
Tomić B, Gvozdenov M, Cumbo M, Dunjić Manevski S, Đorđević V. Nasledni faktori rizika za trombofiliju – od tačkastih mutacija do primene veštačke inteligencije. in Treći kongres biologa Srbije. 2022;:278.
https://hdl.handle.net/21.15107/rcub_imagine_1739 .
Tomić, Branko, Gvozdenov, Maja, Cumbo, Marija, Dunjić Manevski, Sofija, Đorđević, Valentina, "Nasledni faktori rizika za trombofiliju – od tačkastih mutacija do primene veštačke inteligencije" in Treći kongres biologa Srbije (2022):278,
https://hdl.handle.net/21.15107/rcub_imagine_1739 .

Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype

Pruner, Iva; Dinčić, Evica; Gvozdenov, Maja; Tomić, Branko; Kovač, Mirjana; Đorđević, Valentina

(2022)

TY  - JOUR
AU  - Pruner, Iva
AU  - Dinčić, Evica
AU  - Gvozdenov, Maja
AU  - Tomić, Branko
AU  - Kovač, Mirjana
AU  - Đorđević, Valentina
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1646
AB  - Introduction. Ischemic stroke (IS) is a heterogeneous dis-order caused by several genetic and environmental risk factors. It was suggested that coagulation disorders cause 1-4% of cases with IS, especially in patients with early onset of IS. Case report. We describe a case of a young adult male who developed an unprovoked IS. Biochemical, immunological, and thrombophilia screening, as well as DNA sequencing, were performed in order to reveal molecular pathology underlying the stroke of the patient. Thrombophilia testing showed that patient was a homozygous carrier for PAI-1 4G/5G and MTHFR C677T mutations. Additional genetic analysis revealed the presence of the recently reported F2 c.1824C>T gene variant, located in the last exon of the pro-thrombin gene and has previously been shown to cause hy-perprothrombinemia, hypofibrinolysis, and altered fibrin clot phenotype. Conclusion. Our results suggest that the newly reported F2 c.1824C>T gene variant might have a synergistic effect with PAI 4G/4G and MTHFR 677TT genotype in the formation of altered fibrin clot phenotype characterized by thin, densely packed fibrin fibers, which makes clot less susceptible to fibrinolysis and greatly in-creases the risk for early ischemic stroke onset.
AB  - Ishemijski moždani udar (IMU) je heterogeni poremećaj
koji može biti uzrokovan genetskim faktorima rizika i faktorima
sredine. Poremećaji koagulacije mogu biti uzročnici u 1-4%
slučajeva IMU, naročito kod bolesnika kod kojih se IMU dogodi u
mlađem životnom dobu. Prikaz bolesnika. Prikazan je slučaj
bolesnika koji je u mlađem životnom dobu razvio IMU
nepoznatog uzroka. Urađeni su biohemijski, imunološki i testovi za
trombofiliju kao i sekvenciranje DNK sa ciljem da se utvrdi
molekularna patologija koja je mogla biti u osnovi moždanog udara
kod tog bolesnika. Testovima za trombofiliju utvrđeno je da je
bolesnik homozigotni nosilac mutacija PAI-1 4G/5G i MTHFR
C677T. Dodatnom genetičkom analizom otkriveno je prisustvo
nedavno opisane F2 c.1824C>T genske varijante, koja se nalazi u
poslednjem egzonu gena za protrombin i za koju je prethodno
pokazano da izaziva hiperprotrombinemiju, hipofibrinolizu i
izmenjeni fenotip fibrinskog ugruška. Zaključak. Naši rezultati
ukazuju na to da bi nova F2 c.1824C>T genska varijanta mogla
imati sinergistički efekat sa PAI 4G/4G i MTHFR 677TT
genotipom u nastanku fibrinskog ugruška sa izmenjenim
fenotipom, koji se odlikuje tankim, gusto upakovanim fibrinskim
vlaknima, što čini ugrušak manje podložnim fibrinolizi i povećava
rizik od nastanka IMU u ranijem životnom dobu.
T2  - Vojnosanitetski pregled
T2  - Vojnosanitetski pregled
T1  - Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype
EP  - 1043
IS  - 10
SP  - 1039
VL  - 79
DO  - doi.org/10.2298/VSP210323066P
ER  - 
@article{
author = "Pruner, Iva and Dinčić, Evica and Gvozdenov, Maja and Tomić, Branko and Kovač, Mirjana and Đorđević, Valentina",
year = "2022",
abstract = "Introduction. Ischemic stroke (IS) is a heterogeneous dis-order caused by several genetic and environmental risk factors. It was suggested that coagulation disorders cause 1-4% of cases with IS, especially in patients with early onset of IS. Case report. We describe a case of a young adult male who developed an unprovoked IS. Biochemical, immunological, and thrombophilia screening, as well as DNA sequencing, were performed in order to reveal molecular pathology underlying the stroke of the patient. Thrombophilia testing showed that patient was a homozygous carrier for PAI-1 4G/5G and MTHFR C677T mutations. Additional genetic analysis revealed the presence of the recently reported F2 c.1824C>T gene variant, located in the last exon of the pro-thrombin gene and has previously been shown to cause hy-perprothrombinemia, hypofibrinolysis, and altered fibrin clot phenotype. Conclusion. Our results suggest that the newly reported F2 c.1824C>T gene variant might have a synergistic effect with PAI 4G/4G and MTHFR 677TT genotype in the formation of altered fibrin clot phenotype characterized by thin, densely packed fibrin fibers, which makes clot less susceptible to fibrinolysis and greatly in-creases the risk for early ischemic stroke onset., Ishemijski moždani udar (IMU) je heterogeni poremećaj
koji može biti uzrokovan genetskim faktorima rizika i faktorima
sredine. Poremećaji koagulacije mogu biti uzročnici u 1-4%
slučajeva IMU, naročito kod bolesnika kod kojih se IMU dogodi u
mlađem životnom dobu. Prikaz bolesnika. Prikazan je slučaj
bolesnika koji je u mlađem životnom dobu razvio IMU
nepoznatog uzroka. Urađeni su biohemijski, imunološki i testovi za
trombofiliju kao i sekvenciranje DNK sa ciljem da se utvrdi
molekularna patologija koja je mogla biti u osnovi moždanog udara
kod tog bolesnika. Testovima za trombofiliju utvrđeno je da je
bolesnik homozigotni nosilac mutacija PAI-1 4G/5G i MTHFR
C677T. Dodatnom genetičkom analizom otkriveno je prisustvo
nedavno opisane F2 c.1824C>T genske varijante, koja se nalazi u
poslednjem egzonu gena za protrombin i za koju je prethodno
pokazano da izaziva hiperprotrombinemiju, hipofibrinolizu i
izmenjeni fenotip fibrinskog ugruška. Zaključak. Naši rezultati
ukazuju na to da bi nova F2 c.1824C>T genska varijanta mogla
imati sinergistički efekat sa PAI 4G/4G i MTHFR 677TT
genotipom u nastanku fibrinskog ugruška sa izmenjenim
fenotipom, koji se odlikuje tankim, gusto upakovanim fibrinskim
vlaknima, što čini ugrušak manje podložnim fibrinolizi i povećava
rizik od nastanka IMU u ranijem životnom dobu.",
journal = "Vojnosanitetski pregled, Vojnosanitetski pregled",
title = "Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype",
pages = "1043-1039",
number = "10",
volume = "79",
doi = "doi.org/10.2298/VSP210323066P"
}
Pruner, I., Dinčić, E., Gvozdenov, M., Tomić, B., Kovač, M.,& Đorđević, V.. (2022). Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype. in Vojnosanitetski pregled, 79(10), 1039-1043.
https://doi.org/doi.org/10.2298/VSP210323066P
Pruner I, Dinčić E, Gvozdenov M, Tomić B, Kovač M, Đorđević V. Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype. in Vojnosanitetski pregled. 2022;79(10):1039-1043.
doi:doi.org/10.2298/VSP210323066P .
Pruner, Iva, Dinčić, Evica, Gvozdenov, Maja, Tomić, Branko, Kovač, Mirjana, Đorđević, Valentina, "Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype" in Vojnosanitetski pregled, 79, no. 10 (2022):1039-1043,
https://doi.org/doi.org/10.2298/VSP210323066P . .

Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among adults - a pilot study in the Republic of Serbia

Beletić, Anđelo; Dudvarski-Ilić, A.; Nagorni-Obradović, L.; Milenković, B.; Ljujić, Mila; Radojković, Dragica; Đorđević, Valentina; Stanković, S.

(Elsevier, Amsterdam, 2022)

TY  - CONF
AU  - Beletić, Anđelo
AU  - Dudvarski-Ilić, A.
AU  - Nagorni-Obradović, L.
AU  - Milenković, B.
AU  - Ljujić, Mila
AU  - Radojković, Dragica
AU  - Đorđević, Valentina
AU  - Stanković, S.
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1597
PB  - Elsevier, Amsterdam
C3  - Clinica Chimica Acta
T1  - Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among adults - a pilot study in the Republic of Serbia
EP  - S345
SP  - S344
VL  - 530
DO  - 10.1016/j.cca.2022.04.893
ER  - 
@conference{
author = "Beletić, Anđelo and Dudvarski-Ilić, A. and Nagorni-Obradović, L. and Milenković, B. and Ljujić, Mila and Radojković, Dragica and Đorđević, Valentina and Stanković, S.",
year = "2022",
publisher = "Elsevier, Amsterdam",
journal = "Clinica Chimica Acta",
title = "Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among adults - a pilot study in the Republic of Serbia",
pages = "S345-S344",
volume = "530",
doi = "10.1016/j.cca.2022.04.893"
}
Beletić, A., Dudvarski-Ilić, A., Nagorni-Obradović, L., Milenković, B., Ljujić, M., Radojković, D., Đorđević, V.,& Stanković, S.. (2022). Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among adults - a pilot study in the Republic of Serbia. in Clinica Chimica Acta
Elsevier, Amsterdam., 530, S344-S345.
https://doi.org/10.1016/j.cca.2022.04.893
Beletić A, Dudvarski-Ilić A, Nagorni-Obradović L, Milenković B, Ljujić M, Radojković D, Đorđević V, Stanković S. Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among adults - a pilot study in the Republic of Serbia. in Clinica Chimica Acta. 2022;530:S344-S345.
doi:10.1016/j.cca.2022.04.893 .
Beletić, Anđelo, Dudvarski-Ilić, A., Nagorni-Obradović, L., Milenković, B., Ljujić, Mila, Radojković, Dragica, Đorđević, Valentina, Stanković, S., "Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among adults - a pilot study in the Republic of Serbia" in Clinica Chimica Acta, 530 (2022):S344-S345,
https://doi.org/10.1016/j.cca.2022.04.893 . .

The prothrombin Belgrade mutation causing antithrombin resistance does not affect fibrin clot formation

Dunjić, Sofija; Cumbo, Marija; Gvozdenov, Maja; Taxiarchis, Apostolos; Tomić, Branko; Antović, Jovan; Đorđević, Valentina

(2020)

TY  - CONF
AU  - Dunjić, Sofija
AU  - Cumbo, Marija
AU  - Gvozdenov, Maja
AU  - Taxiarchis, Apostolos
AU  - Tomić, Branko
AU  - Antović, Jovan
AU  - Đorđević, Valentina
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1635
AB  - Prothrombin Belgrade mutation is a result of the c.1787G>T
mutation in the prothrombin gene, which leads to the substitution of
Arg596 by Gln. This mutation is located in the antithrombin binding site
and leads to the impaired inactivation of thrombin by antithrombin and
antithrombin resistance, resulting in a thrombotic phenotype. Previous
studies have shown the complex mechanism of this mutation, manifested with higher endogenous thrombin potential, lower prothrombin
activity with normal prothrombin levels in carriers’ plasma.
C3  - Research and Practice in Thrombosis and Haemostasis
C3  - Research and Practice in Thrombosis and Haemostasis
T1  - The prothrombin Belgrade mutation causing antithrombin resistance does not affect fibrin clot formation
EP  - 1117
IS  - 1
SP  - 1117
VL  - 4
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1635
ER  - 
@conference{
author = "Dunjić, Sofija and Cumbo, Marija and Gvozdenov, Maja and Taxiarchis, Apostolos and Tomić, Branko and Antović, Jovan and Đorđević, Valentina",
year = "2020",
abstract = "Prothrombin Belgrade mutation is a result of the c.1787G>T
mutation in the prothrombin gene, which leads to the substitution of
Arg596 by Gln. This mutation is located in the antithrombin binding site
and leads to the impaired inactivation of thrombin by antithrombin and
antithrombin resistance, resulting in a thrombotic phenotype. Previous
studies have shown the complex mechanism of this mutation, manifested with higher endogenous thrombin potential, lower prothrombin
activity with normal prothrombin levels in carriers’ plasma.",
journal = "Research and Practice in Thrombosis and Haemostasis, Research and Practice in Thrombosis and Haemostasis",
title = "The prothrombin Belgrade mutation causing antithrombin resistance does not affect fibrin clot formation",
pages = "1117-1117",
number = "1",
volume = "4",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1635"
}
Dunjić, S., Cumbo, M., Gvozdenov, M., Taxiarchis, A., Tomić, B., Antović, J.,& Đorđević, V.. (2020). The prothrombin Belgrade mutation causing antithrombin resistance does not affect fibrin clot formation. in Research and Practice in Thrombosis and Haemostasis, 4(1), 1117-1117.
https://hdl.handle.net/21.15107/rcub_imagine_1635
Dunjić S, Cumbo M, Gvozdenov M, Taxiarchis A, Tomić B, Antović J, Đorđević V. The prothrombin Belgrade mutation causing antithrombin resistance does not affect fibrin clot formation. in Research and Practice in Thrombosis and Haemostasis. 2020;4(1):1117-1117.
https://hdl.handle.net/21.15107/rcub_imagine_1635 .
Dunjić, Sofija, Cumbo, Marija, Gvozdenov, Maja, Taxiarchis, Apostolos, Tomić, Branko, Antović, Jovan, Đorđević, Valentina, "The prothrombin Belgrade mutation causing antithrombin resistance does not affect fibrin clot formation" in Research and Practice in Thrombosis and Haemostasis, 4, no. 1 (2020):1117-1117,
https://hdl.handle.net/21.15107/rcub_imagine_1635 .

The Silence Speaks, but We Do Not Listen: Synonymous c.1824C gt T Gene Variant in the Last Exon of the Prothrombin Gene as a New Prothrombotic Risk Factor

Pruner, Iva; Farm, Maria; Tomić, Branko; Gvozdenov, Maja; Kovač, Mirjana; Miljić, Predrag; Soutari, Nida Mahmoud Hourani; Antović, Aleksandra; Radojković, Dragica; Antović, Jovan P.; Đorđević, Valentina

(Oxford Univ Press Inc, Cary, 2020)

TY  - JOUR
AU  - Pruner, Iva
AU  - Farm, Maria
AU  - Tomić, Branko
AU  - Gvozdenov, Maja
AU  - Kovač, Mirjana
AU  - Miljić, Predrag
AU  - Soutari, Nida Mahmoud Hourani
AU  - Antović, Aleksandra
AU  - Radojković, Dragica
AU  - Antović, Jovan P.
AU  - Đorđević, Valentina
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1375
AB  - BACKGROUND: Thrombosis is a major global disease burden with almost 60% of cases related to underlying heredity and most cases still idiopathic. Synonymous single nucleotide polymorphisms (sSNPs) are considered silent and phenotypically neutral. Our previous study revealed a novel synonymous FII c.1824C gt  T variant as a potential risk factor for pregnancy loss, but it has not yet been associated with thrombotic diseases. METHODS: To determine the frequency of the FII c.1824C gt  T variant we have sequenced patients' DNA. Prothrombin RNA expression was measured by quantitative PCR. Functional analyses included routine hemostasis tests, western blotting and ELISA to determine prothrombin levels in plasma, and global hemostasis assays for thrombin and fibrin generation in carriers of the FII c.1824C gt  T variant. Scanning electron mi- croscopy was used to examine the structure of fibrin clots. RESULTS: Frequency of the FII c.1824C gt  T variant was significantly increased in patients with venous thromboembolism and cerebrovascular insult. Examination in vitro demonstrated increased expression of prothrombin mRNA in FII c.1824C gt  T transfected cells. Our ex vivo study of FII c.1824C gt  T carriers showed that the presence of this variant was associated with hyperprothrom-binemia, hypofibrinolysis, and formation of densely packed fibrin clots resistant to fibrinolysis. CONCLUSION: Our data indicate that FII c.1824C gt  T, although a synonymous variant, leads to the development of a prothrombotic phenotype and could represent a new prothrombotic risk factor. As a silent variant, FII c.1824C gt  T would probably be overlooked during genetic screening, and our results show that it could not be detected in routine laboratory tests.
PB  - Oxford Univ Press Inc, Cary
T2  - Clinical Chemistry
T1  - The Silence Speaks, but We Do Not Listen: Synonymous c.1824C  gt  T Gene Variant in the Last Exon of the Prothrombin Gene as a New Prothrombotic Risk Factor
EP  - 389
IS  - 2
SP  - 379
VL  - 66
DO  - 10.1093/clinchem/hvz015
ER  - 
@article{
author = "Pruner, Iva and Farm, Maria and Tomić, Branko and Gvozdenov, Maja and Kovač, Mirjana and Miljić, Predrag and Soutari, Nida Mahmoud Hourani and Antović, Aleksandra and Radojković, Dragica and Antović, Jovan P. and Đorđević, Valentina",
year = "2020",
abstract = "BACKGROUND: Thrombosis is a major global disease burden with almost 60% of cases related to underlying heredity and most cases still idiopathic. Synonymous single nucleotide polymorphisms (sSNPs) are considered silent and phenotypically neutral. Our previous study revealed a novel synonymous FII c.1824C gt  T variant as a potential risk factor for pregnancy loss, but it has not yet been associated with thrombotic diseases. METHODS: To determine the frequency of the FII c.1824C gt  T variant we have sequenced patients' DNA. Prothrombin RNA expression was measured by quantitative PCR. Functional analyses included routine hemostasis tests, western blotting and ELISA to determine prothrombin levels in plasma, and global hemostasis assays for thrombin and fibrin generation in carriers of the FII c.1824C gt  T variant. Scanning electron mi- croscopy was used to examine the structure of fibrin clots. RESULTS: Frequency of the FII c.1824C gt  T variant was significantly increased in patients with venous thromboembolism and cerebrovascular insult. Examination in vitro demonstrated increased expression of prothrombin mRNA in FII c.1824C gt  T transfected cells. Our ex vivo study of FII c.1824C gt  T carriers showed that the presence of this variant was associated with hyperprothrom-binemia, hypofibrinolysis, and formation of densely packed fibrin clots resistant to fibrinolysis. CONCLUSION: Our data indicate that FII c.1824C gt  T, although a synonymous variant, leads to the development of a prothrombotic phenotype and could represent a new prothrombotic risk factor. As a silent variant, FII c.1824C gt  T would probably be overlooked during genetic screening, and our results show that it could not be detected in routine laboratory tests.",
publisher = "Oxford Univ Press Inc, Cary",
journal = "Clinical Chemistry",
title = "The Silence Speaks, but We Do Not Listen: Synonymous c.1824C  gt  T Gene Variant in the Last Exon of the Prothrombin Gene as a New Prothrombotic Risk Factor",
pages = "389-379",
number = "2",
volume = "66",
doi = "10.1093/clinchem/hvz015"
}
Pruner, I., Farm, M., Tomić, B., Gvozdenov, M., Kovač, M., Miljić, P., Soutari, N. M. H., Antović, A., Radojković, D., Antović, J. P.,& Đorđević, V.. (2020). The Silence Speaks, but We Do Not Listen: Synonymous c.1824C  gt  T Gene Variant in the Last Exon of the Prothrombin Gene as a New Prothrombotic Risk Factor. in Clinical Chemistry
Oxford Univ Press Inc, Cary., 66(2), 379-389.
https://doi.org/10.1093/clinchem/hvz015
Pruner I, Farm M, Tomić B, Gvozdenov M, Kovač M, Miljić P, Soutari NMH, Antović A, Radojković D, Antović JP, Đorđević V. The Silence Speaks, but We Do Not Listen: Synonymous c.1824C  gt  T Gene Variant in the Last Exon of the Prothrombin Gene as a New Prothrombotic Risk Factor. in Clinical Chemistry. 2020;66(2):379-389.
doi:10.1093/clinchem/hvz015 .
Pruner, Iva, Farm, Maria, Tomić, Branko, Gvozdenov, Maja, Kovač, Mirjana, Miljić, Predrag, Soutari, Nida Mahmoud Hourani, Antović, Aleksandra, Radojković, Dragica, Antović, Jovan P., Đorđević, Valentina, "The Silence Speaks, but We Do Not Listen: Synonymous c.1824C  gt  T Gene Variant in the Last Exon of the Prothrombin Gene as a New Prothrombotic Risk Factor" in Clinical Chemistry, 66, no. 2 (2020):379-389,
https://doi.org/10.1093/clinchem/hvz015 . .
2
8
7

Frequency of FV Leiden and FII G20210A Mutations in Patients with Inherited Antithrombin Deficiency from Serbia

Tomić, Branko; Kovač, Mirjana; Pruner, Iva; Gvozdenov, Maja; Dunjić, Sofija; Cumbo, Marija; Radojković, Dragica; Đorđević, Valentina

(2019)

TY  - CONF
AU  - Tomić, Branko
AU  - Kovač, Mirjana
AU  - Pruner, Iva
AU  - Gvozdenov, Maja
AU  - Dunjić, Sofija
AU  - Cumbo, Marija
AU  - Radojković, Dragica
AU  - Đorđević, Valentina
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2145
AB  - PURPOSE: Thrombosis is multicausal disease in which both acquired and genetic risk factors play
important roles. The most frequent genetic risk factors known to date are the Factor V G1691A (FV
Leiden) and FII G20210A mutations. On the other hand, inherited antithrombin (AT) deficiency, caused
by mutations in the AT gene (SERPINC1) is a very rare disorder, but it is associated with significant risk
for thrombotic complications. AT deficiency is classified into two types: type-I is a quantitative disorder
characterized by decreased amount and activity of AT, while type-II is a qualitative - functional disorder.
Aim of our study was to analyze the frequency of FV Leiden and FII G20210A mutations in patients with
inherited AT deficiency from Serbia.
METHODOLOGY: A study was carried out in large group of AT deficiency patients from Serbia. Cohort
of 42 subjects (15m/27f; 36.7±18.7y) from 18 Serbian families included 24 symptomatic and 18
asymptomatic first-degree relatives. Among them, type-I AT deficiency were detected in 9 families (19
members: 6m/13f; 37.1±19.0y) and type-II in 9 families (23 members: 9m/14f; 36.5±18.8y). FV Leiden
and FII G2010A mutations were detected by PCR, followed by digestion with specific restriction enzymes
(PCR-RFLP).
RESULTS: We have detected 3 FV Leiden heterozygous carriers in 3 different families (1 with type-I
and 2 with type-II AT deficiency). All 3 carriers were symptomatic. Regarding FII G20210A mutation, 2
heterozygous carriers, both asymptomatic and from same family with type-I deficiency, were identified.
According to our findings in families with AT deficiency from Serbia frequency of FV Leiden and FII
G20210A mutation are 16.7% and 5.6%, respectively.
CONCLUSION: This is the first study in which frequency of FV Leiden and FII G20210A mutations in
patients with inherited AT deficiency from Serbia were examined. Results of our study suggest that
these mutations can be relevant for AT deficiency patients’ phenotype, but further studies are required.
C3  - 16th International  Hemophilia Congress of Turkey
T1  - Frequency of FV Leiden and FII G20210A Mutations in Patients with Inherited Antithrombin Deficiency from Serbia
EP  - 212
SP  - 212
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2145
ER  - 
@conference{
author = "Tomić, Branko and Kovač, Mirjana and Pruner, Iva and Gvozdenov, Maja and Dunjić, Sofija and Cumbo, Marija and Radojković, Dragica and Đorđević, Valentina",
year = "2019",
abstract = "PURPOSE: Thrombosis is multicausal disease in which both acquired and genetic risk factors play
important roles. The most frequent genetic risk factors known to date are the Factor V G1691A (FV
Leiden) and FII G20210A mutations. On the other hand, inherited antithrombin (AT) deficiency, caused
by mutations in the AT gene (SERPINC1) is a very rare disorder, but it is associated with significant risk
for thrombotic complications. AT deficiency is classified into two types: type-I is a quantitative disorder
characterized by decreased amount and activity of AT, while type-II is a qualitative - functional disorder.
Aim of our study was to analyze the frequency of FV Leiden and FII G20210A mutations in patients with
inherited AT deficiency from Serbia.
METHODOLOGY: A study was carried out in large group of AT deficiency patients from Serbia. Cohort
of 42 subjects (15m/27f; 36.7±18.7y) from 18 Serbian families included 24 symptomatic and 18
asymptomatic first-degree relatives. Among them, type-I AT deficiency were detected in 9 families (19
members: 6m/13f; 37.1±19.0y) and type-II in 9 families (23 members: 9m/14f; 36.5±18.8y). FV Leiden
and FII G2010A mutations were detected by PCR, followed by digestion with specific restriction enzymes
(PCR-RFLP).
RESULTS: We have detected 3 FV Leiden heterozygous carriers in 3 different families (1 with type-I
and 2 with type-II AT deficiency). All 3 carriers were symptomatic. Regarding FII G20210A mutation, 2
heterozygous carriers, both asymptomatic and from same family with type-I deficiency, were identified.
According to our findings in families with AT deficiency from Serbia frequency of FV Leiden and FII
G20210A mutation are 16.7% and 5.6%, respectively.
CONCLUSION: This is the first study in which frequency of FV Leiden and FII G20210A mutations in
patients with inherited AT deficiency from Serbia were examined. Results of our study suggest that
these mutations can be relevant for AT deficiency patients’ phenotype, but further studies are required.",
journal = "16th International  Hemophilia Congress of Turkey",
title = "Frequency of FV Leiden and FII G20210A Mutations in Patients with Inherited Antithrombin Deficiency from Serbia",
pages = "212-212",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2145"
}
Tomić, B., Kovač, M., Pruner, I., Gvozdenov, M., Dunjić, S., Cumbo, M., Radojković, D.,& Đorđević, V.. (2019). Frequency of FV Leiden and FII G20210A Mutations in Patients with Inherited Antithrombin Deficiency from Serbia. in 16th International  Hemophilia Congress of Turkey, 212-212.
https://hdl.handle.net/21.15107/rcub_imagine_2145
Tomić B, Kovač M, Pruner I, Gvozdenov M, Dunjić S, Cumbo M, Radojković D, Đorđević V. Frequency of FV Leiden and FII G20210A Mutations in Patients with Inherited Antithrombin Deficiency from Serbia. in 16th International  Hemophilia Congress of Turkey. 2019;:212-212.
https://hdl.handle.net/21.15107/rcub_imagine_2145 .
Tomić, Branko, Kovač, Mirjana, Pruner, Iva, Gvozdenov, Maja, Dunjić, Sofija, Cumbo, Marija, Radojković, Dragica, Đorđević, Valentina, "Frequency of FV Leiden and FII G20210A Mutations in Patients with Inherited Antithrombin Deficiency from Serbia" in 16th International  Hemophilia Congress of Turkey (2019):212-212,
https://hdl.handle.net/21.15107/rcub_imagine_2145 .

Inherited thrombophilic risk factors in Serbian breast cancer patients

Pruner, Iva; Tomić, Branko; Dragojević, Marija; Gvozdenov, Maja; Kovač, Mirjana; Radojković, Dragica; Đorđević, Valentina

(Društvo genetičara Srbije, Beograd, 2019)

TY  - JOUR
AU  - Pruner, Iva
AU  - Tomić, Branko
AU  - Dragojević, Marija
AU  - Gvozdenov, Maja
AU  - Kovač, Mirjana
AU  - Radojković, Dragica
AU  - Đorđević, Valentina
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1209
AB  - Breast cancer is the leading cause of cancer-related death among women. An increased burden of thrombotic events among breast cancer patients, leading to higher mortality and morbidity rates, is well established. There are a number of genetic risk factors associated with thrombosis, but their contribution to thrombotic tendencies in patients with cancer is not completely elucidated. We aimed to investigate possible role of FV Leiden, FII G20210A, MTHFR C677T and PAI-1 4G/5G gene variants in etiopathology of breast cancer and accompanying thrombosis in cohort of Serbian patients. Our study included 316 subject divided in three groups: breast cancer patients with (97) or without (99) accompanying thrombosis and healthy control group (120). According to our results, the prevalence for all four prothrombotic gene variants were similar in cancer patients with and without thrombosis and no statistically significant difference was observed between these groups. We detected lower frequency of MTHFR 677TT genotype in breast cancer patients when compared to control group (P=0.014; OR=0.145 (95%CI 0.031-0.679)), indicated that MTHFR C677T homozygosity could play a protective role in breast cancer susceptibility. Our study noted the lack of association between common prothrombotic gene variants and increased prothrombotic risk in Serbian breast cancer patients. Also, our results point out possible role of MTHFR 677TT genotype in etiology of breast cancer, but further studies on larger cohort of patients are needed.
PB  - Društvo genetičara Srbije, Beograd
T2  - Genetika-Belgrade
T1  - Inherited thrombophilic risk factors in Serbian breast cancer patients
EP  - 472
IS  - 2
SP  - 463
VL  - 51
DO  - 10.2298/GENSR1902463P
ER  - 
@article{
author = "Pruner, Iva and Tomić, Branko and Dragojević, Marija and Gvozdenov, Maja and Kovač, Mirjana and Radojković, Dragica and Đorđević, Valentina",
year = "2019",
abstract = "Breast cancer is the leading cause of cancer-related death among women. An increased burden of thrombotic events among breast cancer patients, leading to higher mortality and morbidity rates, is well established. There are a number of genetic risk factors associated with thrombosis, but their contribution to thrombotic tendencies in patients with cancer is not completely elucidated. We aimed to investigate possible role of FV Leiden, FII G20210A, MTHFR C677T and PAI-1 4G/5G gene variants in etiopathology of breast cancer and accompanying thrombosis in cohort of Serbian patients. Our study included 316 subject divided in three groups: breast cancer patients with (97) or without (99) accompanying thrombosis and healthy control group (120). According to our results, the prevalence for all four prothrombotic gene variants were similar in cancer patients with and without thrombosis and no statistically significant difference was observed between these groups. We detected lower frequency of MTHFR 677TT genotype in breast cancer patients when compared to control group (P=0.014; OR=0.145 (95%CI 0.031-0.679)), indicated that MTHFR C677T homozygosity could play a protective role in breast cancer susceptibility. Our study noted the lack of association between common prothrombotic gene variants and increased prothrombotic risk in Serbian breast cancer patients. Also, our results point out possible role of MTHFR 677TT genotype in etiology of breast cancer, but further studies on larger cohort of patients are needed.",
publisher = "Društvo genetičara Srbije, Beograd",
journal = "Genetika-Belgrade",
title = "Inherited thrombophilic risk factors in Serbian breast cancer patients",
pages = "472-463",
number = "2",
volume = "51",
doi = "10.2298/GENSR1902463P"
}
Pruner, I., Tomić, B., Dragojević, M., Gvozdenov, M., Kovač, M., Radojković, D.,& Đorđević, V.. (2019). Inherited thrombophilic risk factors in Serbian breast cancer patients. in Genetika-Belgrade
Društvo genetičara Srbije, Beograd., 51(2), 463-472.
https://doi.org/10.2298/GENSR1902463P
Pruner I, Tomić B, Dragojević M, Gvozdenov M, Kovač M, Radojković D, Đorđević V. Inherited thrombophilic risk factors in Serbian breast cancer patients. in Genetika-Belgrade. 2019;51(2):463-472.
doi:10.2298/GENSR1902463P .
Pruner, Iva, Tomić, Branko, Dragojević, Marija, Gvozdenov, Maja, Kovač, Mirjana, Radojković, Dragica, Đorđević, Valentina, "Inherited thrombophilic risk factors in Serbian breast cancer patients" in Genetika-Belgrade, 51, no. 2 (2019):463-472,
https://doi.org/10.2298/GENSR1902463P . .
1
1

Prothrombin 3'end Gene Variants in Patients With Sporadic Colon Adenocarcinoma

Cumbo, Marija; Tomić, Branko; Dunjić Manevski, Sofija; Jovanović, Tamara; Gvozdenov, Maja; Pruner, Iva; Aralica, Gorana; Kapitanović, Sanja; Cacev, Tamara; Đorđević, Valentina

(Int Inst Anticancer Research, Athens, 2019)

TY  - JOUR
AU  - Cumbo, Marija
AU  - Tomić, Branko
AU  - Dunjić Manevski, Sofija
AU  - Jovanović, Tamara
AU  - Gvozdenov, Maja
AU  - Pruner, Iva
AU  - Aralica, Gorana
AU  - Kapitanović, Sanja
AU  - Cacev, Tamara
AU  - Đorđević, Valentina
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1219
AB  - Background/ Aim: Thrombin plays significant roles in various types of cancer. However, the expression levels of prothrombin, the thrombin precursor, in cancer remain unclear. Variants of the 3'end of the prothrombin gene lead to increased prothrombin expression. This study aimed to analyze prothrombin 3'end gene variants in colon tumor and adjacent normal tissue samples. Materials and Methods: The study group consisted of 93 patients suffering from colon adenocarcinoma. The 3'end of the prothrombin gene was analyzed by DNA sequencing. Results: Three variants, all previously associated with increased prothrombin expression were detected. Frequency of the FII 19911G allele was 46.77% and 47.85% in tumor and normal tissue, respectively. For the FII 20210A allele, the detected frequencies were 2.15% and 1.61%, respectively. The frequency of the FII c.1824T allele was 0.54% in both tissues. Four patients showed different genotypes in tumor and normal tissue. Conclusion: Prothrombin 3' end gene variants may play a role in colorectal cancer.
PB  - Int Inst Anticancer Research, Athens
T2  - Anticancer Research
T1  - Prothrombin 3'end Gene Variants in Patients With Sporadic Colon Adenocarcinoma
EP  - 6071
IS  - 11
SP  - 6067
VL  - 39
DO  - 10.21873/anticanres.13814
ER  - 
@article{
author = "Cumbo, Marija and Tomić, Branko and Dunjić Manevski, Sofija and Jovanović, Tamara and Gvozdenov, Maja and Pruner, Iva and Aralica, Gorana and Kapitanović, Sanja and Cacev, Tamara and Đorđević, Valentina",
year = "2019",
abstract = "Background/ Aim: Thrombin plays significant roles in various types of cancer. However, the expression levels of prothrombin, the thrombin precursor, in cancer remain unclear. Variants of the 3'end of the prothrombin gene lead to increased prothrombin expression. This study aimed to analyze prothrombin 3'end gene variants in colon tumor and adjacent normal tissue samples. Materials and Methods: The study group consisted of 93 patients suffering from colon adenocarcinoma. The 3'end of the prothrombin gene was analyzed by DNA sequencing. Results: Three variants, all previously associated with increased prothrombin expression were detected. Frequency of the FII 19911G allele was 46.77% and 47.85% in tumor and normal tissue, respectively. For the FII 20210A allele, the detected frequencies were 2.15% and 1.61%, respectively. The frequency of the FII c.1824T allele was 0.54% in both tissues. Four patients showed different genotypes in tumor and normal tissue. Conclusion: Prothrombin 3' end gene variants may play a role in colorectal cancer.",
publisher = "Int Inst Anticancer Research, Athens",
journal = "Anticancer Research",
title = "Prothrombin 3'end Gene Variants in Patients With Sporadic Colon Adenocarcinoma",
pages = "6071-6067",
number = "11",
volume = "39",
doi = "10.21873/anticanres.13814"
}
Cumbo, M., Tomić, B., Dunjić Manevski, S., Jovanović, T., Gvozdenov, M., Pruner, I., Aralica, G., Kapitanović, S., Cacev, T.,& Đorđević, V.. (2019). Prothrombin 3'end Gene Variants in Patients With Sporadic Colon Adenocarcinoma. in Anticancer Research
Int Inst Anticancer Research, Athens., 39(11), 6067-6071.
https://doi.org/10.21873/anticanres.13814
Cumbo M, Tomić B, Dunjić Manevski S, Jovanović T, Gvozdenov M, Pruner I, Aralica G, Kapitanović S, Cacev T, Đorđević V. Prothrombin 3'end Gene Variants in Patients With Sporadic Colon Adenocarcinoma. in Anticancer Research. 2019;39(11):6067-6071.
doi:10.21873/anticanres.13814 .
Cumbo, Marija, Tomić, Branko, Dunjić Manevski, Sofija, Jovanović, Tamara, Gvozdenov, Maja, Pruner, Iva, Aralica, Gorana, Kapitanović, Sanja, Cacev, Tamara, Đorđević, Valentina, "Prothrombin 3'end Gene Variants in Patients With Sporadic Colon Adenocarcinoma" in Anticancer Research, 39, no. 11 (2019):6067-6071,
https://doi.org/10.21873/anticanres.13814 . .
1
1

Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among pediatric patients - A pilot study

Beletić, Anđelo; Leković, Z.; Zivković, Z.; Radlović, N.; Perisić, V.; Ljujić, Mila; Radojković, Dragica; Đorđević, Valentina; Stanković, S.

(Elsevier, Amsterdam, 2019)

TY  - CONF
AU  - Beletić, Anđelo
AU  - Leković, Z.
AU  - Zivković, Z.
AU  - Radlović, N.
AU  - Perisić, V.
AU  - Ljujić, Mila
AU  - Radojković, Dragica
AU  - Đorđević, Valentina
AU  - Stanković, S.
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1226
AB  - Background-aim
Alpha-1-antitrypsin deficiency (AATD) is an autosomal recessive
disorder characterized by the reduced alpha-1-antitrypsin (AAT)
level in blood. In pediatric patients, it is dominantly tested as a cause
of liver disease, while specific lung diseases might be potentially
regarded as additional indications. Measurement of AAT concentration is useful as a first-line test, although decreased level may be also
encountered in certain acquired conditions. Our aim was to
determine the interpretative cut-off for AAT concentration i.e. level
below which the presence of common AATD-associated alleles might
be suspected.
Methods
We included 37 subjects with clinical indications or familiar
history of AATD: 19 males and 18 females, aged between 2 months
and 19 years. Immunonephelometry was used for measurement of
AAT concentration in serum and PCR-reverse allele specific hybridization assay for detection of Z and S alleles, which are considered as
the common AATD-associated alleles. Kruskal-Wallis test and ROC
analysis were applied in statistical evaluation.
Results
Three cases of AATD (ZZ genotype) and 14 carriers (13
heterozygous for Z and one for S allele) were detected. AAT
concentration (median (min-max)) measured in AATD cases (0.35
(0.31–0.39) g/L), carriers (0.81 (0.56–1.41) g/L) and patients with
no Z and S allele (1.20 (0.91–2.24) g/L) were significantly different
(P b .001). Four carriers (three heterozygous for Z and one for S
allele) had AAT concentration in the reference range (0.9–2.0 g/L).
We identified the level 1.03 g/L as the most appropriate cut-off to
distinguish group comprising both cases of AATD and carriers from
patients in whom no common AATD-associated allele was present.
Corresponding AUC value (95% Confidence interval (CI)) was 0.929
(0.795–0.987) (P b .001). Sensitivity and specificity (95% CI) reached
94.1 (71.3–99.9)% and 90.0 (68.3–98.8)% respectively.
Conclusions
In pediatric patients AAT concentration below 1.03 g/L may be
regarded as a potential cut-off indicating the presence of common
AATD-associated alleles in homo-or heterozygous form. Nevertheless, this preliminary finding needs confirmation in a larger study.
PB  - Elsevier, Amsterdam
C3  - Clinica Chimica Acta
T1  - Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among pediatric patients - A pilot study
EP  - S455
SP  - S455
VL  - 493
DO  - 10.1016/j.cca.2019.03.964
ER  - 
@conference{
author = "Beletić, Anđelo and Leković, Z. and Zivković, Z. and Radlović, N. and Perisić, V. and Ljujić, Mila and Radojković, Dragica and Đorđević, Valentina and Stanković, S.",
year = "2019",
abstract = "Background-aim
Alpha-1-antitrypsin deficiency (AATD) is an autosomal recessive
disorder characterized by the reduced alpha-1-antitrypsin (AAT)
level in blood. In pediatric patients, it is dominantly tested as a cause
of liver disease, while specific lung diseases might be potentially
regarded as additional indications. Measurement of AAT concentration is useful as a first-line test, although decreased level may be also
encountered in certain acquired conditions. Our aim was to
determine the interpretative cut-off for AAT concentration i.e. level
below which the presence of common AATD-associated alleles might
be suspected.
Methods
We included 37 subjects with clinical indications or familiar
history of AATD: 19 males and 18 females, aged between 2 months
and 19 years. Immunonephelometry was used for measurement of
AAT concentration in serum and PCR-reverse allele specific hybridization assay for detection of Z and S alleles, which are considered as
the common AATD-associated alleles. Kruskal-Wallis test and ROC
analysis were applied in statistical evaluation.
Results
Three cases of AATD (ZZ genotype) and 14 carriers (13
heterozygous for Z and one for S allele) were detected. AAT
concentration (median (min-max)) measured in AATD cases (0.35
(0.31–0.39) g/L), carriers (0.81 (0.56–1.41) g/L) and patients with
no Z and S allele (1.20 (0.91–2.24) g/L) were significantly different
(P b .001). Four carriers (three heterozygous for Z and one for S
allele) had AAT concentration in the reference range (0.9–2.0 g/L).
We identified the level 1.03 g/L as the most appropriate cut-off to
distinguish group comprising both cases of AATD and carriers from
patients in whom no common AATD-associated allele was present.
Corresponding AUC value (95% Confidence interval (CI)) was 0.929
(0.795–0.987) (P b .001). Sensitivity and specificity (95% CI) reached
94.1 (71.3–99.9)% and 90.0 (68.3–98.8)% respectively.
Conclusions
In pediatric patients AAT concentration below 1.03 g/L may be
regarded as a potential cut-off indicating the presence of common
AATD-associated alleles in homo-or heterozygous form. Nevertheless, this preliminary finding needs confirmation in a larger study.",
publisher = "Elsevier, Amsterdam",
journal = "Clinica Chimica Acta",
title = "Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among pediatric patients - A pilot study",
pages = "S455-S455",
volume = "493",
doi = "10.1016/j.cca.2019.03.964"
}
Beletić, A., Leković, Z., Zivković, Z., Radlović, N., Perisić, V., Ljujić, M., Radojković, D., Đorđević, V.,& Stanković, S.. (2019). Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among pediatric patients - A pilot study. in Clinica Chimica Acta
Elsevier, Amsterdam., 493, S455-S455.
https://doi.org/10.1016/j.cca.2019.03.964
Beletić A, Leković Z, Zivković Z, Radlović N, Perisić V, Ljujić M, Radojković D, Đorđević V, Stanković S. Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among pediatric patients - A pilot study. in Clinica Chimica Acta. 2019;493:S455-S455.
doi:10.1016/j.cca.2019.03.964 .
Beletić, Anđelo, Leković, Z., Zivković, Z., Radlović, N., Perisić, V., Ljujić, Mila, Radojković, Dragica, Đorđević, Valentina, Stanković, S., "Interpretative cut-off for alpha-1-antitrypsin concentration in detection of alpha-1-antitrypsin deficiency among pediatric patients - A pilot study" in Clinica Chimica Acta, 493 (2019):S455-S455,
https://doi.org/10.1016/j.cca.2019.03.964 . .

Prothrombin expression in cancer-derived cell lines

Dunjić Manevski, Sofija; Cumbo, Marija; Gvozdenov, Maja; Tomić, Branko; Pruner, Iva; Radojković, Dragica; Đorđević, Valentina

(Srpsko biološko društvo, Beograd, i dr., 2019)

TY  - JOUR
AU  - Dunjić Manevski, Sofija
AU  - Cumbo, Marija
AU  - Gvozdenov, Maja
AU  - Tomić, Branko
AU  - Pruner, Iva
AU  - Radojković, Dragica
AU  - Đorđević, Valentina
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1244
AB  - The link between thrombotic disorders and cancer has been known for over 150 years, although the precise mechanism of this relationship has not yet been resolved. Current data show that thrombin has a significant role in cancer metabolism, invasiveness, adhesion and survival. However, data regarding the expression of the thrombin precursor prothrombin in various cancer cell lines are scarce. Therefore, it was our objective to determine whether common cancer-derived cell lines (Caco-2, MCF-7, SK-BR-3, U-87 and U-251) express prothrombin. The prothrombin RNA expression level was assessed by qPCR, and the presence of prothrombin was analyzed by Western blot analysis. Our results show that Caco-2 cells originating from colorectal adenocarcinoma express prothrombin, whereas other analyzed cell lines do not. Our results provide a background for further research into the role of (pro) thrombin in cancer etiopathology.
PB  - Srpsko biološko društvo, Beograd, i dr.
T2  - Archives of Biological Sciences
T1  - Prothrombin expression in cancer-derived cell lines
EP  - 54
IS  - 1
SP  - 49
VL  - 71
DO  - 10.2298/ABS180829046D
ER  - 
@article{
author = "Dunjić Manevski, Sofija and Cumbo, Marija and Gvozdenov, Maja and Tomić, Branko and Pruner, Iva and Radojković, Dragica and Đorđević, Valentina",
year = "2019",
abstract = "The link between thrombotic disorders and cancer has been known for over 150 years, although the precise mechanism of this relationship has not yet been resolved. Current data show that thrombin has a significant role in cancer metabolism, invasiveness, adhesion and survival. However, data regarding the expression of the thrombin precursor prothrombin in various cancer cell lines are scarce. Therefore, it was our objective to determine whether common cancer-derived cell lines (Caco-2, MCF-7, SK-BR-3, U-87 and U-251) express prothrombin. The prothrombin RNA expression level was assessed by qPCR, and the presence of prothrombin was analyzed by Western blot analysis. Our results show that Caco-2 cells originating from colorectal adenocarcinoma express prothrombin, whereas other analyzed cell lines do not. Our results provide a background for further research into the role of (pro) thrombin in cancer etiopathology.",
publisher = "Srpsko biološko društvo, Beograd, i dr.",
journal = "Archives of Biological Sciences",
title = "Prothrombin expression in cancer-derived cell lines",
pages = "54-49",
number = "1",
volume = "71",
doi = "10.2298/ABS180829046D"
}
Dunjić Manevski, S., Cumbo, M., Gvozdenov, M., Tomić, B., Pruner, I., Radojković, D.,& Đorđević, V.. (2019). Prothrombin expression in cancer-derived cell lines. in Archives of Biological Sciences
Srpsko biološko društvo, Beograd, i dr.., 71(1), 49-54.
https://doi.org/10.2298/ABS180829046D
Dunjić Manevski S, Cumbo M, Gvozdenov M, Tomić B, Pruner I, Radojković D, Đorđević V. Prothrombin expression in cancer-derived cell lines. in Archives of Biological Sciences. 2019;71(1):49-54.
doi:10.2298/ABS180829046D .
Dunjić Manevski, Sofija, Cumbo, Marija, Gvozdenov, Maja, Tomić, Branko, Pruner, Iva, Radojković, Dragica, Đorđević, Valentina, "Prothrombin expression in cancer-derived cell lines" in Archives of Biological Sciences, 71, no. 1 (2019):49-54,
https://doi.org/10.2298/ABS180829046D . .
2

Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis

Vucković, Biljana A.; Đerić, Mirjana J.; Tomić, Branko; Đorđević, Valentina; Bajkin, Branislav V.; Mitić, Gorana P.

(Lippincott Williams & Wilkins, Philadelphia, 2018)

TY  - JOUR
AU  - Vucković, Biljana A.
AU  - Đerić, Mirjana J.
AU  - Tomić, Branko
AU  - Đorđević, Valentina
AU  - Bajkin, Branislav V.
AU  - Mitić, Gorana P.
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1177
AB  - Objective of our study is to determine whether decreased fibrinolytic activity or plasminogen activator inhibitor (PAI)-1 4G/5G polymorphism influence the risk of venous thrombosis. Our case-control study included 100 patients with venous thrombosis, and 100 random controls. When patients were compared with random controls, unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Decreased fibrinolytic activity yielded a 2.7-fold increase in risk for venous thrombosis than physiological fibrinolytic activity (OR 2.70; 95% CI 1.22-5.98), when comparing patients with random controls. Adjustment for several putative confounders did not change the estimate (OR 3.02; 95% CI 1.26-7.22). Analysis of venous thrombotic risk influenced by PAI-1 genotype, showed no influence of PAI-1 4G/5G gene variant in comparison with 5G/5G genotype (OR 0.57 95% CI; 0.27-1.20). Decreased fibrinolytic activity increased, whereas PAI-1 4G/5G polymorphism did not influence venous thrombosis risk in this study.
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Blood Coagulation & Fibrinolysis
T1  - Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis
EP  - 24
IS  - 1
SP  - 19
VL  - 29
DO  - 10.1097/MBC.0000000000000656
ER  - 
@article{
author = "Vucković, Biljana A. and Đerić, Mirjana J. and Tomić, Branko and Đorđević, Valentina and Bajkin, Branislav V. and Mitić, Gorana P.",
year = "2018",
abstract = "Objective of our study is to determine whether decreased fibrinolytic activity or plasminogen activator inhibitor (PAI)-1 4G/5G polymorphism influence the risk of venous thrombosis. Our case-control study included 100 patients with venous thrombosis, and 100 random controls. When patients were compared with random controls, unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Decreased fibrinolytic activity yielded a 2.7-fold increase in risk for venous thrombosis than physiological fibrinolytic activity (OR 2.70; 95% CI 1.22-5.98), when comparing patients with random controls. Adjustment for several putative confounders did not change the estimate (OR 3.02; 95% CI 1.26-7.22). Analysis of venous thrombotic risk influenced by PAI-1 genotype, showed no influence of PAI-1 4G/5G gene variant in comparison with 5G/5G genotype (OR 0.57 95% CI; 0.27-1.20). Decreased fibrinolytic activity increased, whereas PAI-1 4G/5G polymorphism did not influence venous thrombosis risk in this study.",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Blood Coagulation & Fibrinolysis",
title = "Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis",
pages = "24-19",
number = "1",
volume = "29",
doi = "10.1097/MBC.0000000000000656"
}
Vucković, B. A., Đerić, M. J., Tomić, B., Đorđević, V., Bajkin, B. V.,& Mitić, G. P.. (2018). Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis. in Blood Coagulation & Fibrinolysis
Lippincott Williams & Wilkins, Philadelphia., 29(1), 19-24.
https://doi.org/10.1097/MBC.0000000000000656
Vucković BA, Đerić MJ, Tomić B, Đorđević V, Bajkin BV, Mitić GP. Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis. in Blood Coagulation & Fibrinolysis. 2018;29(1):19-24.
doi:10.1097/MBC.0000000000000656 .
Vucković, Biljana A., Đerić, Mirjana J., Tomić, Branko, Đorđević, Valentina, Bajkin, Branislav V., Mitić, Gorana P., "Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis" in Blood Coagulation & Fibrinolysis, 29, no. 1 (2018):19-24,
https://doi.org/10.1097/MBC.0000000000000656 . .
2
7
1
10

Evaluation of endogenous thrombin potential among patients with antithrombin deficiency

Kovač, Mirjana; Mitić, Gorana; Lalić-Cosić, Sanja; Đorđević, Valentina; Tomić, Branko; Muszbek, Laszlo; Bereczky, Zsuzsanna

(Pergamon-Elsevier Science Ltd, Oxford, 2018)

TY  - JOUR
AU  - Kovač, Mirjana
AU  - Mitić, Gorana
AU  - Lalić-Cosić, Sanja
AU  - Đorđević, Valentina
AU  - Tomić, Branko
AU  - Muszbek, Laszlo
AU  - Bereczky, Zsuzsanna
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1108
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Thrombosis Research
T1  - Evaluation of endogenous thrombin potential among patients with antithrombin deficiency
EP  - 53
SP  - 50
VL  - 166
DO  - 10.1016/j.thromres.2018.04.004
ER  - 
@article{
author = "Kovač, Mirjana and Mitić, Gorana and Lalić-Cosić, Sanja and Đorđević, Valentina and Tomić, Branko and Muszbek, Laszlo and Bereczky, Zsuzsanna",
year = "2018",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Thrombosis Research",
title = "Evaluation of endogenous thrombin potential among patients with antithrombin deficiency",
pages = "53-50",
volume = "166",
doi = "10.1016/j.thromres.2018.04.004"
}
Kovač, M., Mitić, G., Lalić-Cosić, S., Đorđević, V., Tomić, B., Muszbek, L.,& Bereczky, Z.. (2018). Evaluation of endogenous thrombin potential among patients with antithrombin deficiency. in Thrombosis Research
Pergamon-Elsevier Science Ltd, Oxford., 166, 50-53.
https://doi.org/10.1016/j.thromres.2018.04.004
Kovač M, Mitić G, Lalić-Cosić S, Đorđević V, Tomić B, Muszbek L, Bereczky Z. Evaluation of endogenous thrombin potential among patients with antithrombin deficiency. in Thrombosis Research. 2018;166:50-53.
doi:10.1016/j.thromres.2018.04.004 .
Kovač, Mirjana, Mitić, Gorana, Lalić-Cosić, Sanja, Đorđević, Valentina, Tomić, Branko, Muszbek, Laszlo, Bereczky, Zsuzsanna, "Evaluation of endogenous thrombin potential among patients with antithrombin deficiency" in Thrombosis Research, 166 (2018):50-53,
https://doi.org/10.1016/j.thromres.2018.04.004 . .
4
2

Functional analyses of the FIIc.*64_*66del gene variant and its potential role in fetal loss etiology

Gvozdenov, Maja; Pruner, Iva; Tomić, Branko; Kovač, Mirjana; Miljić, Predrag; Antić, Darko; Đorđević, Valentina; Radojković, Dragica

(Nature Publishing Group, London, 2018)

TY  - CONF
AU  - Gvozdenov, Maja
AU  - Pruner, Iva
AU  - Tomić, Branko
AU  - Kovač, Mirjana
AU  - Miljić, Predrag
AU  - Antić, Darko
AU  - Đorđević, Valentina
AU  - Radojković, Dragica
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1136
PB  - Nature Publishing Group, London
C3  - European Journal of Human Genetics
T1  - Functional analyses of the FIIc.*64_*66del gene variant and its potential role in fetal loss etiology
EP  - 828
SP  - 827
VL  - 26
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1136
ER  - 
@conference{
author = "Gvozdenov, Maja and Pruner, Iva and Tomić, Branko and Kovač, Mirjana and Miljić, Predrag and Antić, Darko and Đorđević, Valentina and Radojković, Dragica",
year = "2018",
publisher = "Nature Publishing Group, London",
journal = "European Journal of Human Genetics",
title = "Functional analyses of the FIIc.*64_*66del gene variant and its potential role in fetal loss etiology",
pages = "828-827",
volume = "26",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1136"
}
Gvozdenov, M., Pruner, I., Tomić, B., Kovač, M., Miljić, P., Antić, D., Đorđević, V.,& Radojković, D.. (2018). Functional analyses of the FIIc.*64_*66del gene variant and its potential role in fetal loss etiology. in European Journal of Human Genetics
Nature Publishing Group, London., 26, 827-828.
https://hdl.handle.net/21.15107/rcub_imagine_1136
Gvozdenov M, Pruner I, Tomić B, Kovač M, Miljić P, Antić D, Đorđević V, Radojković D. Functional analyses of the FIIc.*64_*66del gene variant and its potential role in fetal loss etiology. in European Journal of Human Genetics. 2018;26:827-828.
https://hdl.handle.net/21.15107/rcub_imagine_1136 .
Gvozdenov, Maja, Pruner, Iva, Tomić, Branko, Kovač, Mirjana, Miljić, Predrag, Antić, Darko, Đorđević, Valentina, Radojković, Dragica, "Functional analyses of the FIIc.*64_*66del gene variant and its potential role in fetal loss etiology" in European Journal of Human Genetics, 26 (2018):827-828,
https://hdl.handle.net/21.15107/rcub_imagine_1136 .

Are Prothrombotic Mutations a Time-to-Event Risk Factor?

Tomić, Branko; Gvozdenov, Maja; Pruner, Iva; Simić, Jelena M.; Kovač, Mirjana; Radojković, Dragica ; Đorđević, Valentina

(Oxford Univ Press, Oxford, 2017)

TY  - JOUR
AU  - Tomić, Branko
AU  - Gvozdenov, Maja
AU  - Pruner, Iva
AU  - Simić, Jelena M.
AU  - Kovač, Mirjana
AU  - Radojković, Dragica 
AU  - Đorđević, Valentina
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1025
AB  - Background: Deep vein thrombosis (DVT) represents a common disorder involving genetic and acquired risk factors. It has been proposed that acquired risk factors are more important with aging than genetic factors, indicating different prevalence of prothrombotic mutations throughout the lifespan. Objective: To determine the role of the most frequent prothrombotic genetic risk factors (Factor V [FV] Leiden and Factor II [FII] G20210A mutations) in first-time DVT etiology in patients of different ages. Method: This retrospective study included 701 patients living in Serbia with diagnosed DVT as a first-time thrombotic event. Results: Risk assessment for mutations as age-related markers showed no statistical difference (FV Leiden mutation-OR, 1.027; 95% confidence interval [CI],.87-1.22; P=.76 and FII G20210A mutation-OR, 0.940, 95% CI,.74-1.19; P=.61). Our results show similar mutation prevalence regardless of how old the patients were at the time of the first DVT occurrence. Conclusion: Our results indicate that these 2 mutations cannot be used as prognostic marker for time-to-event first DVT in the Serbian population; however, further studies are required.
PB  - Oxford Univ Press, Oxford
T2  - Laboratory Medicine
T1  - Are Prothrombotic Mutations a Time-to-Event Risk Factor?
EP  - 331
IS  - 4
SP  - 326
VL  - 48
DO  - 10.1093/labmed/lmx046
ER  - 
@article{
author = "Tomić, Branko and Gvozdenov, Maja and Pruner, Iva and Simić, Jelena M. and Kovač, Mirjana and Radojković, Dragica  and Đorđević, Valentina",
year = "2017",
abstract = "Background: Deep vein thrombosis (DVT) represents a common disorder involving genetic and acquired risk factors. It has been proposed that acquired risk factors are more important with aging than genetic factors, indicating different prevalence of prothrombotic mutations throughout the lifespan. Objective: To determine the role of the most frequent prothrombotic genetic risk factors (Factor V [FV] Leiden and Factor II [FII] G20210A mutations) in first-time DVT etiology in patients of different ages. Method: This retrospective study included 701 patients living in Serbia with diagnosed DVT as a first-time thrombotic event. Results: Risk assessment for mutations as age-related markers showed no statistical difference (FV Leiden mutation-OR, 1.027; 95% confidence interval [CI],.87-1.22; P=.76 and FII G20210A mutation-OR, 0.940, 95% CI,.74-1.19; P=.61). Our results show similar mutation prevalence regardless of how old the patients were at the time of the first DVT occurrence. Conclusion: Our results indicate that these 2 mutations cannot be used as prognostic marker for time-to-event first DVT in the Serbian population; however, further studies are required.",
publisher = "Oxford Univ Press, Oxford",
journal = "Laboratory Medicine",
title = "Are Prothrombotic Mutations a Time-to-Event Risk Factor?",
pages = "331-326",
number = "4",
volume = "48",
doi = "10.1093/labmed/lmx046"
}
Tomić, B., Gvozdenov, M., Pruner, I., Simić, J. M., Kovač, M., Radojković, D.,& Đorđević, V.. (2017). Are Prothrombotic Mutations a Time-to-Event Risk Factor?. in Laboratory Medicine
Oxford Univ Press, Oxford., 48(4), 326-331.
https://doi.org/10.1093/labmed/lmx046
Tomić B, Gvozdenov M, Pruner I, Simić JM, Kovač M, Radojković D, Đorđević V. Are Prothrombotic Mutations a Time-to-Event Risk Factor?. in Laboratory Medicine. 2017;48(4):326-331.
doi:10.1093/labmed/lmx046 .
Tomić, Branko, Gvozdenov, Maja, Pruner, Iva, Simić, Jelena M., Kovač, Mirjana, Radojković, Dragica , Đorđević, Valentina, "Are Prothrombotic Mutations a Time-to-Event Risk Factor?" in Laboratory Medicine, 48, no. 4 (2017):326-331,
https://doi.org/10.1093/labmed/lmx046 . .

Clinical and biochemical characterization of the prothrombin Belgrade mutation in a large Serbian pedigree: new insights into the antithrombin resistance mechanism

Miljić, Predrag; Gvozdenov, Maja; Takagi, Y.; Takagi, A.; Pruner, Iva; Dragojević, M.; Tomić, Branko; Bodrozić, J.; Kojima, T.; Radojković, Dragica; Đorđević, Valentina

(Wiley, Hoboken, 2017)

TY  - JOUR
AU  - Miljić, Predrag
AU  - Gvozdenov, Maja
AU  - Takagi, Y.
AU  - Takagi, A.
AU  - Pruner, Iva
AU  - Dragojević, M.
AU  - Tomić, Branko
AU  - Bodrozić, J.
AU  - Kojima, T.
AU  - Radojković, Dragica
AU  - Đorđević, Valentina
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1045
AB  - Background: The recently reported c.1787G gt A mutation in the prothrombin gene leads to Arg596Gln replacement in the protein molecule (prothrombin Belgrade). This substitution impairs binding of antithrombin to thrombin and results in inherited thrombophilia, known as antithrombin resistance. Objectives: We aimed to elucidate the clinical and biochemical characteristics of thrombophilia associated with antithrombin resistance in a large Serbian family with the prothrombin Belgrade mutation. Patients and methods: Nineteen family members were investigated, among whom 10 were carriers of the c.1787G gt A mutation. In all subjects the clinical phenotype was determined and laboratory investigations of hemostatic parameters were performed. Results: Six out of the 10 mutation carriers developed thromboembolic events, mainly deep venous and mesenteric vein thrombosis. The median age of the first thrombotic event was 26.5 (12-41) years, whereas the incidence rate of first thrombosis was 2.2% per year. In all mutation carriers prothrombin activity was significantly decreased in comparison with non-carriers, clearly distinguishing each group. However, the presence of the mutation did not affect the prothrombin antigen level in plasma. The endogenous thrombin potential was significantly increased in all carriers in comparison with non-carriers, indicating the presence of blood hypercoagulability. Interestingly, levels of D-dimer and the F1+2 fragment were similar in both groups. Conclusions: Although rare, the prothrombin Belgrade mutation represents strong thrombophilia with early onset of thrombosis in the investigated family. According to our results, decreased prothrombin activity may be a simple screening test for detection of this mutation in thrombotic patients.
PB  - Wiley, Hoboken
T2  - Journal of Thrombosis and Haemostasis
T1  - Clinical and biochemical characterization of the prothrombin Belgrade mutation in a large Serbian pedigree: new insights into the antithrombin resistance mechanism
EP  - 677
IS  - 4
SP  - 670
VL  - 15
DO  - 10.1111/jth.13618
ER  - 
@article{
author = "Miljić, Predrag and Gvozdenov, Maja and Takagi, Y. and Takagi, A. and Pruner, Iva and Dragojević, M. and Tomić, Branko and Bodrozić, J. and Kojima, T. and Radojković, Dragica and Đorđević, Valentina",
year = "2017",
abstract = "Background: The recently reported c.1787G gt A mutation in the prothrombin gene leads to Arg596Gln replacement in the protein molecule (prothrombin Belgrade). This substitution impairs binding of antithrombin to thrombin and results in inherited thrombophilia, known as antithrombin resistance. Objectives: We aimed to elucidate the clinical and biochemical characteristics of thrombophilia associated with antithrombin resistance in a large Serbian family with the prothrombin Belgrade mutation. Patients and methods: Nineteen family members were investigated, among whom 10 were carriers of the c.1787G gt A mutation. In all subjects the clinical phenotype was determined and laboratory investigations of hemostatic parameters were performed. Results: Six out of the 10 mutation carriers developed thromboembolic events, mainly deep venous and mesenteric vein thrombosis. The median age of the first thrombotic event was 26.5 (12-41) years, whereas the incidence rate of first thrombosis was 2.2% per year. In all mutation carriers prothrombin activity was significantly decreased in comparison with non-carriers, clearly distinguishing each group. However, the presence of the mutation did not affect the prothrombin antigen level in plasma. The endogenous thrombin potential was significantly increased in all carriers in comparison with non-carriers, indicating the presence of blood hypercoagulability. Interestingly, levels of D-dimer and the F1+2 fragment were similar in both groups. Conclusions: Although rare, the prothrombin Belgrade mutation represents strong thrombophilia with early onset of thrombosis in the investigated family. According to our results, decreased prothrombin activity may be a simple screening test for detection of this mutation in thrombotic patients.",
publisher = "Wiley, Hoboken",
journal = "Journal of Thrombosis and Haemostasis",
title = "Clinical and biochemical characterization of the prothrombin Belgrade mutation in a large Serbian pedigree: new insights into the antithrombin resistance mechanism",
pages = "677-670",
number = "4",
volume = "15",
doi = "10.1111/jth.13618"
}
Miljić, P., Gvozdenov, M., Takagi, Y., Takagi, A., Pruner, I., Dragojević, M., Tomić, B., Bodrozić, J., Kojima, T., Radojković, D.,& Đorđević, V.. (2017). Clinical and biochemical characterization of the prothrombin Belgrade mutation in a large Serbian pedigree: new insights into the antithrombin resistance mechanism. in Journal of Thrombosis and Haemostasis
Wiley, Hoboken., 15(4), 670-677.
https://doi.org/10.1111/jth.13618
Miljić P, Gvozdenov M, Takagi Y, Takagi A, Pruner I, Dragojević M, Tomić B, Bodrozić J, Kojima T, Radojković D, Đorđević V. Clinical and biochemical characterization of the prothrombin Belgrade mutation in a large Serbian pedigree: new insights into the antithrombin resistance mechanism. in Journal of Thrombosis and Haemostasis. 2017;15(4):670-677.
doi:10.1111/jth.13618 .
Miljić, Predrag, Gvozdenov, Maja, Takagi, Y., Takagi, A., Pruner, Iva, Dragojević, M., Tomić, Branko, Bodrozić, J., Kojima, T., Radojković, Dragica, Đorđević, Valentina, "Clinical and biochemical characterization of the prothrombin Belgrade mutation in a large Serbian pedigree: new insights into the antithrombin resistance mechanism" in Journal of Thrombosis and Haemostasis, 15, no. 4 (2017):670-677,
https://doi.org/10.1111/jth.13618 . .
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