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 .

TY  - JOUR
AU  - Dunjić Manevski, Sofija
AU  - Cumbo, Marija
AU  - Pruner, Iva
AU  - Gvozdenov, Maja
AU  - Tomić, Branko
AU  - Taxiarchis, Apostolos
AU  - Antović, Jovan
AU  - Đordjević, Valentina
PY  - 2023
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1111/ijlh.14195
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2199
AB  - Introduction Prothrombin Belgrade mutation is the result of the c.1787G>A substitution in the prothrombin gene. It is located in the antithrombin and sodium binding site and leads to impaired inactivation of thrombin by antithrombin, resulting in antithrombin resistance and thrombotic disorders. However, it negatively affects sodium binding and may have hypocoagulant effects. Considering that prothrombin Belgrade mutation mechanism is still not fully elucidated and that sodium binding is important for thrombin affinity towards fibrinogen, our aim was to determine whether this mutation affects fibrin clot formation and lysis. Methods Using HEK293T cell line, recombinant wild type and mutated prothrombin were generated by transient transfection. Samples that correspond to plasma of a non-carrier, heterozygous and homozygous carriers were reconstituted using prothrombin deficient plasma and recombinant proteins. Reconstituted samples were used in OHP assay (Overall Hemostasis Potential) to determine kinetic profiles of coagulation and fibrinolysis. Clot turbidity assay was performed to observe kinetics of clot formation and lysis more closely. Fibrin clots formed in reconstituted plasma samples were analyzed by confocal microscopy to determine density of fibrin network. Fibrin clots were additionally observed using electron microscopy to determine thickness of individual fibrin fibers. Results No significant difference found in OHP, OCP, OFP, and fibrin network density between wild type, heterozygous, and homozygous carrier reconstituted plasma samples. There were significant differences between samples for slope and slope time parameters in kinetic profiles and fibrin fiber thickness. Conclusions Results indicate that prothrombin Belgrade mutation has no significant impact on fibrinolysis, however it may affect kinetics of clot formation and its architecture.
T2  - International Journal of Laboratory Hematology
T1  - Effect of prothrombin Belgrade mutation, causing antithrombin resistance, on fibrin clot properties
VL  - n/a
DO  - 10.1111/ijlh.14195
ER  - 

@article{
author = "Dunjić Manevski, Sofija and Cumbo, Marija and Pruner, Iva and Gvozdenov, Maja and Tomić, Branko and Taxiarchis, Apostolos and Antović, Jovan and Đordjević, Valentina",
year = "2023",
abstract = "Introduction Prothrombin Belgrade mutation is the result of the c.1787G>A substitution in the prothrombin gene. It is located in the antithrombin and sodium binding site and leads to impaired inactivation of thrombin by antithrombin, resulting in antithrombin resistance and thrombotic disorders. However, it negatively affects sodium binding and may have hypocoagulant effects. Considering that prothrombin Belgrade mutation mechanism is still not fully elucidated and that sodium binding is important for thrombin affinity towards fibrinogen, our aim was to determine whether this mutation affects fibrin clot formation and lysis. Methods Using HEK293T cell line, recombinant wild type and mutated prothrombin were generated by transient transfection. Samples that correspond to plasma of a non-carrier, heterozygous and homozygous carriers were reconstituted using prothrombin deficient plasma and recombinant proteins. Reconstituted samples were used in OHP assay (Overall Hemostasis Potential) to determine kinetic profiles of coagulation and fibrinolysis. Clot turbidity assay was performed to observe kinetics of clot formation and lysis more closely. Fibrin clots formed in reconstituted plasma samples were analyzed by confocal microscopy to determine density of fibrin network. Fibrin clots were additionally observed using electron microscopy to determine thickness of individual fibrin fibers. Results No significant difference found in OHP, OCP, OFP, and fibrin network density between wild type, heterozygous, and homozygous carrier reconstituted plasma samples. There were significant differences between samples for slope and slope time parameters in kinetic profiles and fibrin fiber thickness. Conclusions Results indicate that prothrombin Belgrade mutation has no significant impact on fibrinolysis, however it may affect kinetics of clot formation and its architecture.",
journal = "International Journal of Laboratory Hematology",
title = "Effect of prothrombin Belgrade mutation, causing antithrombin resistance, on fibrin clot properties",
volume = "n/a",
doi = "10.1111/ijlh.14195"
}

Dunjić Manevski, S., Cumbo, M., Pruner, I., Gvozdenov, M., Tomić, B., Taxiarchis, A., Antović, J.,& Đordjević, V.. (2023). Effect of prothrombin Belgrade mutation, causing antithrombin resistance, on fibrin clot properties. in International Journal of Laboratory Hematology, n/a.
https://doi.org/10.1111/ijlh.14195

Dunjić Manevski S, Cumbo M, Pruner I, Gvozdenov M, Tomić B, Taxiarchis A, Antović J, Đordjević V. Effect of prothrombin Belgrade mutation, causing antithrombin resistance, on fibrin clot properties. in International Journal of Laboratory Hematology. 2023;n/a.
doi:10.1111/ijlh.14195 .

Dunjić Manevski, Sofija, Cumbo, Marija, Pruner, Iva, Gvozdenov, Maja, Tomić, Branko, Taxiarchis, Apostolos, Antović, Jovan, Đordjević, Valentina, "Effect of prothrombin Belgrade mutation, causing antithrombin resistance, on fibrin clot properties" in International Journal of Laboratory Hematology, n/a (2023),
https://doi.org/10.1111/ijlh.14195 . .

TY  - CONF
AU  - Dunjić Manevski, Sofija
AU  - Cumbo, Marija
AU  - Gvozdenov, Maja
AU  - Tomić, Branko
AU  - Ušjak, Dušan
AU  - Đorđević
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2126
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_2126
ER  - 

@conference{
author = "Dunjić Manevski, Sofija and Cumbo, Marija and Gvozdenov, Maja and Tomić, Branko and Ušjak, Dušan and Đorđević",
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_2126"
}

Dunjić Manevski, S., Cumbo, M., Gvozdenov, M., Tomić, B., Ušjak, D.,& Đorđević. (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_2126

Dunjić Manevski S, Cumbo M, Gvozdenov M, Tomić B, Ušjak D, Đorđević. 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_2126 .

Dunjić Manevski, Sofija, Cumbo, Marija, Gvozdenov, Maja, Tomić, Branko, Ušjak, Dušan, Đorđević, "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_2126 .

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 .

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 .

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 .

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 .

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 .

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 .

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 . .

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 . .